this study aims to examine factors related to volunteerism and explore the relationship between volunteerism and positive aging across three age groups . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 23 . 1 this 2 study 2 study 3 aims 3 aims 4 to 4 to 10 and 5 examine 6 factors 5 examine 7 related 5 examine 10 and 6 factors 7 related 7 related 8 to 8 to 9 volunteerism 10 and 11 explore 10 and 16 and 12 the 13 relationship 13 relationship 14 between 13 relationship 16 and 14 between 15 volunteerism 16 and 17 positive 16 and 18 aging 18 aging 19 across 19 across 22 groups 20 three 22 groups 21 age 22 groups a total of 1,170 hong kong chinese respondents aged between 15 years and 79 years were recruited for the study via a random household survey . 0 ###LEFT-WALL### 2 total 0 ###LEFT-WALL### 9 aged 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 26 . 1 a 2 total 2 total 3 of 2 total 9 aged 3 of 8 respondents 4 1,170 8 respondents 5 hong 6 kong 6 kong 8 respondents 7 chinese 8 respondents 9 aged 10 between 10 between 12 years 11 15 12 years 13 and 15 years 13 and 17 recruited 14 79 15 years 15 years 16 were 16 were 17 recruited 17 recruited 18 for 17 recruited 21 via 18 for 20 study 19 the 20 study 21 via 25 survey 22 a 23 random 22 a 25 survey 23 random 24 household 24 household 25 survey results found that age was negatively related to participation in voluntary work . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 found 0 ###LEFT-WALL### 13 . 1 results 2 found 2 found 3 that 3 that 4 age 3 that 7 related 4 age 5 was 5 was 6 negatively 5 was 7 related 7 related 8 to 7 related 10 in 8 to 9 participation 10 in 12 work 11 voluntary 12 work older adults aged 60 years to 75 years demonstrated the lowest volunteer participation rate compared with younger adults ( aged 15 years to 39 years ) and midlife adults ( aged 40 years to 59 years ) . 0 ###LEFT-WALL### 2 adults 0 ###LEFT-WALL### 3 aged 0 ###LEFT-WALL### 38 . 1 older 2 adults 2 adults 3 aged 3 aged 5 years 4 60 5 years 5 years 8 years 5 years 9 demonstrated 6 to 7 75 6 to 8 years 8 years 9 demonstrated 9 demonstrated 27 and 10 the 11 lowest 10 the 14 rate 12 volunteer 14 rate 13 participation 14 rate 14 rate 15 compared 14 rate 16 with 14 rate 27 and 16 with 18 adults 17 younger 18 adults 18 adults 22 years 19 ( 22 years 20 aged 22 years 21 15 22 years 22 years 23 to 22 years 26 ) 23 to 25 years 24 39 25 years 27 and 29 adults 27 and 33 years 28 midlife 29 adults 30 ( 33 years 31 aged 33 years 32 40 33 years 33 years 34 to 33 years 37 ) 34 to 36 years 35 59 36 years paradoxically , older volunteers exhibited the highest frequency of volunteering , operationalized as spending 10 hours or more on volunteer work in the past month . 0 ###LEFT-WALL### 4 volunteers 0 ###LEFT-WALL### 11 , 0 ###LEFT-WALL### 26 . 1 paradoxically 2 , 1 paradoxically 4 volunteers 3 older 4 volunteers 4 volunteers 11 , 5 exhibited 8 frequency 5 exhibited 11 , 6 the 7 highest 6 the 8 frequency 8 frequency 9 of 9 of 10 volunteering 11 , 12 operationalized 11 , 13 as 13 as 14 spending 14 spending 15 10 14 spending 17 or 16 hours 17 or 17 or 18 more 17 or 19 on 17 or 22 in 19 on 21 work 20 volunteer 21 work 22 in 25 month 23 the 24 past 23 the 25 month compared with younger [and] midlife adults , older adults were motivated to volunteer by societal concern and esteem enhancement . 0 ###LEFT-WALL### 9 adults 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 20 . 1 compared 2 with 1 compared 7 , 1 compared 9 adults 2 with 6 adults 3 younger 5 midlife 5 midlife 6 adults 8 older 9 adults 9 adults 17 and 10 were 11 motivated 10 were 17 and 11 motivated 12 to 11 motivated 13 volunteer 12 to 13 volunteer 13 volunteer 14 by 14 by 16 concern 15 societal 16 concern 17 and 18 esteem 17 and 19 enhancement participation in voluntary work was associated with three positive aging outcomes : good health , caring engagement with significant others , and productive engagement in the community . 0 ###LEFT-WALL### 1 participation 0 ###LEFT-WALL### 6 associated 0 ###LEFT-WALL### 12 : 1 participation 2 in 1 participation 5 was 2 in 4 work 3 voluntary 4 work 5 was 6 associated 6 associated 7 with 7 with 11 outcomes 8 three 11 outcomes 9 positive 11 outcomes 10 aging 11 outcomes 12 : 14 health 13 good 14 health 14 health 17 engagement 15 , 17 engagement 16 caring 17 engagement 17 engagement 18 with 17 engagement 28 . 18 with 24 engagement 19 significant 24 engagement 20 others 22 and 21 , 22 and 22 and 23 productive 22 and 24 engagement 24 engagement 25 in 25 in 27 community 26 the 27 community the findings suggest great potential in promoting volunteering in old age because older volunteers tend to contribute more hours than younger volunteers do , and volunteering is associated with positive aging . 0 ###LEFT-WALL### 2 findings 0 ###LEFT-WALL### 3 suggest 0 ###LEFT-WALL### 25 and 0 ###LEFT-WALL### 32 . 1 the 2 findings 2 findings 3 suggest 3 suggest 5 potential 3 suggest 16 to 3 suggest 20 than 4 great 5 potential 5 potential 6 in 5 potential 8 volunteering 6 in 7 promoting 8 volunteering 9 in 8 volunteering 12 because 9 in 11 age 10 old 11 age 12 because 14 volunteers 12 because 15 tend 13 older 14 volunteers 14 volunteers 15 tend 16 to 17 contribute 17 contribute 19 hours 18 more 19 hours 20 than 23 do 21 younger 22 volunteers 22 volunteers 23 do 24 , 25 and 25 and 26 volunteering 25 and 28 associated 26 volunteering 27 is 27 is 28 associated 28 associated 29 with 29 with 31 aging 30 positive 31 aging family - based support has been the traditional care arrangement for the elderly in china . 0 ###LEFT-WALL### 4 support 0 ###LEFT-WALL### 6 been 0 ###LEFT-WALL### 16 . 1 family 2 - 1 family 4 support 3 based 4 support 4 support 5 has 5 has 6 been 6 been 10 arrangement 7 the 10 arrangement 8 traditional 9 care 9 care 10 arrangement 10 arrangement 11 for 10 arrangement 14 in 11 for 13 elderly 12 the 13 elderly 14 in 15 china with the maturing of its " one child per couple " policy and the changing scenarios of family structure and cultural norms , these traditional care arrangements for the chinese [elderly] are becoming dismantled . 0 ###LEFT-WALL### 27 arrangements 0 ###LEFT-WALL### 35 . 1 with 16 scenarios 1 with 23 , 1 with 27 arrangements 2 the 16 scenarios 3 maturing 4 of 3 maturing 13 and 4 of 8 child 5 its 6 " 5 its 7 one 7 one 8 child 8 child 9 per 9 per 12 policy 10 couple 11 " 10 couple 12 policy 13 and 15 changing 13 and 16 scenarios 14 the 15 changing 16 scenarios 17 of 17 of 20 and 18 family 19 structure 19 structure 20 and 20 and 22 norms 20 and 23 , 21 cultural 22 norms 24 these 27 arrangements 25 traditional 26 care 26 care 27 arrangements 27 arrangements 28 for 27 arrangements 32 are 28 for 30 chinese 29 the 30 chinese 32 are 33 becoming 33 becoming 34 dismantled centers and associations within the community have gradually become the major infrastructures to provide old age service and support in china . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 9 become 0 ###LEFT-WALL### 22 . 1 centers 2 and 2 and 3 associations 2 and 4 within 2 and 7 have 4 within 6 community 5 the 6 community 7 have 9 become 8 gradually 9 become 9 become 12 infrastructures 9 become 13 to 10 the 12 infrastructures 11 major 12 infrastructures 13 to 14 provide 14 provide 18 and 14 provide 20 in 15 old 16 age 16 age 17 service 17 service 18 and 18 and 19 support 20 in 21 china this study examined the effects of family - base [d] and community - based support on life satisfaction among older chinese adults , using data from the pilot survey of china health and retirement longitudinal study ( charls ) in 2008 . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 examined 0 ###LEFT-WALL### 42 . 1 this 2 study 2 study 3 examined 3 examined 5 effects 3 examined 14 based 4 the 5 effects 5 effects 6 of 5 effects 11 and 5 effects 14 based 6 of 7 family 8 - 11 and 9 base 11 and 11 and 12 community 11 and 13 - 14 based 15 support 14 based 16 on 16 on 18 satisfaction 17 life 18 satisfaction 18 satisfaction 19 among 19 among 33 and 20 older 22 adults 21 chinese 22 adults 22 adults 23 , 23 , 25 data 23 , 33 and 24 using 25 data 25 data 26 from 26 from 29 survey 27 the 29 survey 28 pilot 29 survey 29 survey 30 of 30 of 32 health 31 china 32 health 33 and 38 charls 33 and 40 in 34 retirement 35 longitudinal 35 longitudinal 36 study 36 study 38 charls 37 ( 38 charls 38 charls 39 ) 40 in 41 2008 a series of multilevel models were assessed with statistical package sas 9.2 among 1,398 chinese adults aged 45 or older . 0 ###LEFT-WALL### 2 series 0 ###LEFT-WALL### 7 assessed 0 ###LEFT-WALL### 21 . 1 a 2 series 2 series 3 of 2 series 6 were 3 of 5 models 4 multilevel 5 models 6 were 7 assessed 7 assessed 8 with 7 assessed 19 or 8 with 11 sas 9 statistical 11 sas 10 package 11 sas 11 sas 12 9.2 11 sas 13 among 13 among 14 1,398 15 chinese 16 adults 16 adults 17 aged 16 adults 19 or 17 aged 18 45 19 or 20 older the results suggest that even with the inclusion of community [-] based support , family - based support variable , the perceived future help from family members , still significantly predicted the life satisfaction among older chinese adults . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 suggest 1 the 2 results 2 results 3 suggest 3 suggest 4 that 3 suggest 12 based 4 that 5 even 4 that 12 based 5 even 6 with 6 with 8 inclusion 7 the 8 inclusion 8 inclusion 9 of 9 of 10 community 12 based 13 support 13 support 15 family 13 support 18 support 14 , 15 family 15 family 16 - 16 - 18 support 17 based 18 support 18 support 28 , 19 variable 24 help 20 , 24 help 21 the 24 help 22 perceived 24 help 23 future 24 help 24 help 25 from 24 help 28 , 25 from 27 members 26 family 27 members 28 , 29 still 28 , 31 predicted 30 significantly 31 predicted 31 predicted 34 satisfaction 31 predicted 35 among 31 predicted 39 . 32 the 34 satisfaction 33 life 34 satisfaction 35 among 38 adults 36 older 38 adults 37 chinese 38 adults data from 365 college students were used to assess young adults ' communicative responses to older persons ' painful self - disclosures ( psds ) . 0 ###LEFT-WALL### 1 data 0 ###LEFT-WALL### 7 used 0 ###LEFT-WALL### 26 . 1 data 2 from 1 data 6 were 2 from 5 students 3 365 5 students 4 college 5 students 6 were 7 used 7 used 8 to 7 used 9 assess 8 to 9 assess 9 assess 14 responses 10 young 11 adults 11 adults 12 ' 12 ' 14 responses 13 communicative 14 responses 14 responses 15 to 15 to 20 self 16 older 17 persons 17 persons 18 ' 18 ' 20 self 19 painful 20 self 20 self 22 disclosures 21 - 22 disclosures 22 disclosures 24 psds 22 disclosures 25 ) 23 ( 24 psds 24 psds 25 ) coupland , coupland , and giles ( 1991 ) proposed that recipients of psd may respond to such disclosures via a variety of"next moves . " 0 ###LEFT-WALL### 1 coupland 0 ###LEFT-WALL### 10 proposed 0 ###LEFT-WALL### 25 . 1 coupland 5 and 1 coupland 10 proposed 2 , 5 and 3 coupland 5 and 4 , 5 and 5 and 6 giles 5 and 8 1991 5 and 9 ) 7 ( 8 1991 8 1991 9 ) 10 proposed 11 that 11 that 12 recipients 11 that 16 respond 12 recipients 13 of 12 recipients 15 may 13 of 14 psd 15 may 16 respond 16 respond 17 to 16 respond 20 via 17 to 19 disclosures 18 such 19 disclosures 20 via 22 variety 21 a 22 variety 22 variety 23 of"next 22 variety 24 moves 23 of"next 24 moves 25 . 26 " these responses may broadly be considered to reflect forms of pro [-] social engagement , passive disengagement , and active disengagement . 0 ###LEFT-WALL### 2 responses 0 ###LEFT-WALL### 6 considered 0 ###LEFT-WALL### 22 . 1 these 2 responses 2 responses 3 may 3 may 5 be 4 broadly 5 be 5 be 6 considered 6 considered 7 to 6 considered 8 reflect 7 to 8 reflect 8 reflect 9 forms 9 forms 10 of 10 of 19 and 11 pro 14 engagement 13 social 14 engagement 14 engagement 15 , 15 , 17 disengagement 15 , 19 and 16 passive 17 disengagement 18 , 19 and 19 and 21 disengagement 20 active 21 disengagement we investigated whether young adults ' tendency to use certain responses to psd were influenced by their affective reactions to psd , their communicative background and characteristics , and the sociorelational context of the encounter in which psd occurred . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 investigated 0 ###LEFT-WALL### 22 , 0 ###LEFT-WALL### 40 . 1 we 2 investigated 2 investigated 3 whether 2 investigated 7 tendency 3 whether 4 young 5 adults 6 ' 6 ' 7 tendency 7 tendency 8 to 7 tendency 11 responses 7 tendency 14 were 7 tendency 15 influenced 8 to 9 use 10 certain 11 responses 11 responses 12 to 11 responses 14 were 12 to 13 psd 15 influenced 16 by 16 by 19 reactions 17 their 19 reactions 18 affective 19 reactions 19 reactions 20 to 20 to 21 psd 22 , 29 and 23 their 25 background 24 communicative 25 background 25 background 26 and 26 and 27 characteristics 26 and 28 , 26 and 29 and 28 , 29 and 29 and 32 context 29 and 33 of 30 the 32 context 31 sociorelational 32 context 33 of 35 encounter 34 the 35 encounter 35 encounter 36 in 36 in 37 which 36 in 38 psd 36 in 39 occurred 38 psd 39 occurred results are discussed with respect to their implications for intergenerational interaction , and [interpreted] through the lens of communication accommodation theory . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 3 discussed 0 ###LEFT-WALL### 22 . 1 results 2 are 2 are 3 discussed 3 discussed 4 with 3 discussed 6 to 3 discussed 13 and 4 with 5 respect 6 to 8 implications 7 their 8 implications 9 for 11 interaction 9 for 13 and 10 intergenerational 11 interaction 12 , 13 and 13 and 15 through 15 through 17 lens 16 the 17 lens 17 lens 18 of 18 of 21 theory 19 communication 21 theory 20 accommodation 21 theory on the example of 5437 employees of enterprises and institutions of the kemerovo region , compiled into 14 occupational groups [,] an analysis of the relationship between age structure and the frequency of arterial hypertension due to the working conditions [has] [been] performed at high levels of hardness of employment and the impact of physical factors , [a] shift in the age structure toward younger age is seen , which is considered as a demographic consequence of professional ageing . 1 on 3 example 1 on 6 employees 2 the 3 example 4 of 5 5437 4 of 6 employees 6 employees 7 of 6 employees 16 compiled 7 of 9 and 8 enterprises 9 and 9 and 10 institutions 9 and 15 , 10 institutions 11 of 11 of 14 region 12 the 14 region 13 kemerovo 14 region 16 compiled 17 into 16 compiled 23 analysis 17 into 20 groups 18 14 20 groups 19 occupational 20 groups 22 an 23 analysis 23 analysis 24 of 23 analysis 27 between 24 of 26 relationship 25 the 26 relationship 27 between 30 and 28 age 29 structure 29 structure 30 and 30 and 32 frequency 31 the 32 frequency 32 frequency 33 of 32 frequency 37 to 33 of 35 hypertension 34 arterial 35 hypertension 36 due 37 to 37 to 46 levels 38 the 46 levels 39 working 46 levels 40 conditions 43 performed 43 performed 46 levels 44 at 46 levels 45 high 46 levels 46 levels 47 of 46 levels 49 of 47 of 48 hardness 49 of 59 shift 50 employment 51 and 51 and 53 impact 51 and 57 , 51 and 59 shift 52 the 53 impact 53 impact 54 of 54 of 56 factors 55 physical 56 factors 59 shift 60 in 59 shift 70 which 60 in 62 age 61 the 62 age 62 age 63 structure 62 age 67 is 62 age 68 seen 63 structure 64 toward 63 structure 67 is 64 toward 66 age 65 younger 66 age 69 , 70 which 70 which 71 is 70 which 80 . 71 is 72 considered 72 considered 73 as 73 as 76 consequence 74 a 76 consequence 75 demographic 76 consequence 76 consequence 77 of 77 of 79 ageing 78 professional 79 ageing in turn , expressed professional ageing causes the reduction in the prevalence [of] hypertension , which is , probably is implemented by the effect [of] ["] healthy worker " . 0 ###LEFT-WALL### 6 ageing 0 ###LEFT-WALL### 7 causes 0 ###LEFT-WALL### 15 , 0 ###LEFT-WALL### 30 . 1 in 2 turn 2 turn 3 , 2 turn 6 ageing 4 expressed 6 ageing 5 professional 6 ageing 6 ageing 7 causes 7 causes 9 reduction 7 causes 10 in 8 the 9 reduction 10 in 14 hypertension 11 the 14 hypertension 12 prevalence 14 hypertension 15 , 16 which 15 , 18 , 16 which 18 , 17 is 18 , 18 , 20 is 19 probably 20 is 20 is 21 implemented 21 implemented 22 by 22 by 28 worker 23 the 28 worker 24 effect 28 worker 27 healthy 28 worker 28 worker 29 " since our birth , we are programmed to experience predetermined stages of life whose passage is inevitable as the passage of time ( childhood , youth , adulthood , old age ) . 0 ###LEFT-WALL### 5 we 0 ###LEFT-WALL### 7 programmed 0 ###LEFT-WALL### 33 . 1 since 3 birth 1 since 4 , 1 since 5 we 2 our 3 birth 5 we 6 are 6 are 7 programmed 7 programmed 8 to 7 programmed 9 experience 8 to 9 experience 9 experience 11 stages 10 predetermined 11 stages 11 stages 12 of 11 stages 14 whose 11 stages 24 childhood 12 of 13 life 14 whose 15 passage 15 passage 16 is 16 is 17 inevitable 17 inevitable 18 as 18 as 20 passage 19 the 20 passage 20 passage 21 of 21 of 22 time 23 ( 24 childhood 24 childhood 26 youth 24 childhood 31 age 24 childhood 32 ) 25 , 26 youth 26 youth 28 adulthood 26 youth 29 , 27 , 28 adulthood 28 adulthood 29 , 29 , 31 age 30 old 31 age 31 age 32 ) although each of these stages of development differs in its specific tasks , the old age seems to be the most burdensome , resulting in significant changes : physical and intellectual decline , major changes in the importance of the professional , marital , parental and social role . 0 ###LEFT-WALL### 16 age 0 ###LEFT-WALL### 17 seems 0 ###LEFT-WALL### 28 : 1 although 2 each 1 although 8 differs 1 although 13 , 1 although 16 age 2 each 3 of 2 each 8 differs 3 of 5 stages 4 these 5 stages 5 stages 6 of 6 of 7 development 8 differs 9 in 9 in 12 tasks 10 its 12 tasks 11 specific 12 tasks 14 the 16 age 15 old 16 age 16 age 17 seems 17 seems 18 to 17 seems 19 be 18 to 19 be 19 be 21 most 19 be 22 burdensome 20 the 21 most 22 burdensome 24 resulting 23 , 24 resulting 24 resulting 25 in 24 resulting 28 : 25 in 27 changes 26 significant 27 changes 28 : 30 and 28 : 33 , 28 : 49 . 29 physical 30 and 30 and 31 intellectual 30 and 33 , 32 decline 33 , 33 , 34 major 33 , 46 and 35 changes 36 in 35 changes 42 , 36 in 38 importance 37 the 38 importance 38 importance 39 of 39 of 41 professional 40 the 41 professional 42 , 43 marital 42 , 44 , 44 , 45 parental 44 , 46 and 46 and 48 role 47 social 48 role one of the main indicators of the quality of life , the average life expectancy increased significantly in the last 3 - 4 decades and the mankind gained decades of active life in a relatively short period of time . 0 ###LEFT-WALL### 25 and 0 ###LEFT-WALL### 28 gained 0 ###LEFT-WALL### 40 . 1 one 2 of 1 one 11 , 2 of 5 indicators 3 the 4 main 3 the 5 indicators 5 indicators 6 of 6 of 8 quality 7 the 8 quality 8 quality 9 of 9 of 10 life 11 , 15 expectancy 11 , 25 and 12 the 15 expectancy 13 average 14 life 14 life 15 expectancy 15 expectancy 16 increased 16 increased 17 significantly 16 increased 18 in 18 in 24 decades 19 the 20 last 19 the 22 - 21 3 22 - 22 - 23 4 22 - 24 decades 25 and 27 mankind 25 and 28 gained 26 the 27 mankind 28 gained 29 decades 28 gained 33 in 29 decades 30 of 30 of 32 life 31 active 32 life 33 in 37 period 34 a 35 relatively 34 a 37 period 35 relatively 36 short 36 short 37 period 37 period 38 of 38 of 39 time therefore , one of the goals of medicine has become the prolongation of life , the pursuit of old age , the wish to remain healthy , to be able of physical and intellectual performance and useful in the private and social life . 1 therefore 2 , 1 therefore 3 one 3 one 4 of 3 one 9 has 4 of 6 goals 5 the 6 goals 6 goals 7 of 7 of 8 medicine 9 has 10 become 10 become 12 prolongation 11 the 12 prolongation 12 prolongation 13 of 13 of 14 life 14 life 17 pursuit 15 , 17 pursuit 16 the 17 pursuit 17 pursuit 18 of 17 pursuit 44 . 18 of 20 age 19 old 20 age 20 age 23 wish 21 , 23 wish 22 the 23 wish 23 wish 24 to 23 wish 25 remain 23 wish 26 healthy 23 wish 44 . 24 to 25 remain 26 healthy 28 to 27 , 28 to 28 to 29 be 28 to 44 . 29 be 36 and 29 be 38 in 30 able 31 of 30 able 36 and 31 of 33 and 32 physical 33 and 33 and 35 performance 34 intellectual 35 performance 36 and 37 useful 38 in 41 and 39 the 40 private 40 private 41 and 41 and 43 life 42 social 43 life the old age is conditioned by a complex combination of factors : the individual genetic predisposition , the lifestyle of society and the environment , all of which affect the opinions regarding health and subsequently the attitude towards health . 0 ###LEFT-WALL### 3 age 0 ###LEFT-WALL### 4 is 0 ###LEFT-WALL### 12 : 0 ###LEFT-WALL### 40 . 1 the 3 age 2 old 3 age 3 age 4 is 4 is 5 conditioned 5 conditioned 6 by 6 by 9 combination 7 a 9 combination 8 complex 9 combination 9 combination 10 of 10 of 11 factors 12 : 16 predisposition 12 : 17 , 13 the 16 predisposition 14 individual 16 predisposition 15 genetic 16 predisposition 17 , 22 and 17 , 25 , 18 the 19 lifestyle 19 lifestyle 20 of 19 lifestyle 22 and 20 of 21 society 22 and 24 environment 23 the 24 environment 25 , 26 all 25 , 29 affect 26 all 27 of 26 all 29 affect 27 of 28 which 29 affect 31 opinions 29 affect 38 towards 30 the 31 opinions 31 opinions 32 regarding 32 regarding 34 and 33 health 34 and 34 and 35 subsequently 34 and 37 attitude 36 the 37 attitude 38 towards 39 health the family physician has the social obligation to research and [promote] health , to fight diseases . 0 ###LEFT-WALL### 3 physician 0 ###LEFT-WALL### 4 has 0 ###LEFT-WALL### 13 , 0 ###LEFT-WALL### 17 . 1 the 3 physician 2 family 3 physician 3 physician 4 has 4 has 7 obligation 4 has 8 to 5 the 7 obligation 6 social 7 obligation 8 to 10 and 9 research 10 and 10 and 12 health 13 , 14 to 13 , 15 fight 14 to 15 fight 15 fight 16 diseases the family physician achieves this by researching the aging field and by trying to find solutions to improve the quality of life in the elderly , which is a prerequisite of maintaining the integration of the elderly into family life and society , of preserving the biological and social independence of aged persons . 0 ###LEFT-WALL### 3 physician 0 ###LEFT-WALL### 4 achieves 1 the 3 physician 2 family 3 physician 3 physician 4 achieves 4 achieves 5 this 4 achieves 11 and 6 by 7 researching 6 by 11 and 7 researching 10 field 8 the 10 field 9 aging 10 field 11 and 12 by 12 by 13 trying 13 trying 14 to 13 trying 15 find 14 to 15 find 15 find 16 solutions 15 find 17 to 17 to 18 improve 18 improve 20 quality 19 the 20 quality 20 quality 21 of 20 quality 27 which 21 of 22 life 22 life 23 in 23 in 25 elderly 24 the 25 elderly 26 , 27 which 27 which 28 is 27 which 54 . 28 is 41 and 29 a 30 prerequisite 30 prerequisite 31 of 30 prerequisite 41 and 31 of 32 maintaining 32 maintaining 34 integration 32 maintaining 38 into 33 the 34 integration 34 integration 35 of 35 of 37 elderly 36 the 37 elderly 38 into 40 life 39 family 40 life 41 and 42 society 41 and 43 , 41 and 44 of 44 of 45 preserving 45 preserving 50 independence 46 the 50 independence 47 biological 48 and 48 and 49 social 48 and 50 independence 50 independence 51 of 51 of 53 persons 52 aged 53 persons the maintenance of an active private and social life is a method of fighting premature aging associated with infirmity and disease . 0 ###LEFT-WALL### 2 maintenance 0 ###LEFT-WALL### 10 is 0 ###LEFT-WALL### 22 . 1 the 2 maintenance 2 maintenance 3 of 2 maintenance 10 is 3 of 7 and 4 an 5 active 4 an 6 private 5 active 6 private 6 private 7 and 7 and 9 life 8 social 9 life 10 is 20 and 11 a 12 method 12 method 13 of 12 method 20 and 13 of 14 fighting 14 fighting 16 aging 14 fighting 18 with 15 premature 16 aging 16 aging 17 associated 18 with 19 infirmity 20 and 21 disease this action cannot be successful without the active involvement of the elderly and without their acceptance in the society . 0 ###LEFT-WALL### 2 action 0 ###LEFT-WALL### 4 be 0 ###LEFT-WALL### 20 . 1 this 2 action 2 action 3 cannot 3 cannot 4 be 4 be 5 successful 5 successful 13 and 5 successful 17 in 6 without 9 involvement 6 without 13 and 7 the 9 involvement 8 active 9 involvement 9 involvement 10 of 10 of 12 elderly 11 the 12 elderly 13 and 14 without 14 without 16 acceptance 15 their 16 acceptance 17 in 19 society 18 the 19 society aging is a biological process that affects the entire body , following the period of development and it is considered the final stage of biomorphosis . 0 ###LEFT-WALL### 1 aging 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 11 , 0 ###LEFT-WALL### 26 . 1 aging 2 is 2 is 5 process 3 a 5 process 4 biological 5 process 5 process 6 that 5 process 7 affects 6 that 7 affects 7 affects 10 body 8 the 10 body 9 entire 10 body 11 , 12 following 11 , 20 considered 12 following 14 period 12 following 19 is 13 the 14 period 14 period 15 of 15 of 17 and 16 development 17 and 17 and 18 it 19 is 20 considered 20 considered 23 stage 21 the 23 stage 22 final 23 stage 23 stage 24 of 24 of 25 biomorphosis unlabelled : age related macular degeneration ( amd ) is the most frequent cause of blindness in the elderly . 0 ###LEFT-WALL### 1 unlabelled 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 20 . 2 : 6 degeneration 2 : 10 is 3 age 4 related 4 related 6 degeneration 5 macular 6 degeneration 6 degeneration 8 amd 6 degeneration 10 is 7 ( 8 amd 8 amd 9 ) 10 is 12 most 11 the 12 most 12 most 13 frequent 12 most 17 in 13 frequent 14 cause 14 cause 15 of 15 of 16 blindness 17 in 19 elderly 18 the 19 elderly aim : to establish the role of oxidative stress in retinal structural lesions in amd and to monitor the evolution of oxidative stress markers and oct measurements before and after treatment . 0 ###LEFT-WALL### 1 aim 0 ###LEFT-WALL### 2 : 2 : 3 to 2 : 16 and 2 : 32 . 3 to 16 and 4 establish 6 role 4 establish 10 in 4 establish 14 in 4 establish 16 and 5 the 6 role 6 role 7 of 7 of 9 stress 8 oxidative 9 stress 10 in 13 lesions 11 retinal 13 lesions 12 structural 13 lesions 14 in 15 amd 16 and 17 to 16 and 18 monitor 16 and 29 and 17 to 18 monitor 18 monitor 20 evolution 19 the 20 evolution 20 evolution 21 of 21 of 25 and 22 oxidative 24 markers 23 stress 24 markers 24 markers 25 and 25 and 27 measurements 26 oct 27 measurements 28 before 29 and 29 and 30 after 30 after 31 treatment material and methods : this is a case - control study that included 19 patients diagnosed with amd and 40 matched healthy controls . 0 ###LEFT-WALL### 3 methods 0 ###LEFT-WALL### 4 : 0 ###LEFT-WALL### 24 . 1 material 2 and 2 and 3 methods 4 : 5 this 4 : 6 is 4 : 9 - 4 : 13 included 5 this 6 is 6 is 8 case 7 a 8 case 9 - 10 control 10 control 11 study 11 study 12 that 11 study 13 included 12 that 13 included 13 included 15 patients 13 included 17 with 14 19 15 patients 15 patients 16 diagnosed 17 with 19 and 18 amd 19 and 19 and 23 controls 20 40 23 controls 21 matched 23 controls 22 healthy 23 controls according to the areds classification , patients were divided into mild , moderate and severe amd and received treatment with antioxidants , neurotrophic drugs , intravitreal [corticosteroids] [and/or] anti - vegf . 0 ###LEFT-WALL### 7 patients 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 22 , 0 ###LEFT-WALL### 32 . 1 according 2 to 1 according 5 classification 1 according 6 , 1 according 7 patients 2 to 4 areds 3 the 4 areds 7 patients 17 and 8 were 9 divided 8 were 17 and 9 divided 10 into 10 into 16 amd 11 mild 12 , 12 , 13 moderate 12 , 14 and 14 and 15 severe 14 and 16 amd 17 and 18 received 17 and 20 with 18 received 19 treatment 20 with 21 antioxidants 22 , 24 drugs 22 , 25 , 23 neurotrophic 24 drugs 25 , 31 vegf 26 intravitreal 31 vegf 29 anti 30 - 29 anti 31 vegf we followed the patients by assessment of visual acuity , optical coherence tomography ( oct ) and oxidative stress markers , such as superoxide - dismutase ( sod ) , thiobarbituric acid reactive substances ( tbars ) , [and] c - reactive protein ( crp ) from blood samples before and after treatment . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 followed 0 ###LEFT-WALL### 54 . 1 we 2 followed 2 followed 4 patients 2 followed 5 by 2 followed 23 as 2 followed 51 and 3 the 4 patients 5 by 17 and 6 assessment 7 of 6 assessment 17 and 7 of 9 acuity 8 visual 9 acuity 9 acuity 13 tomography 10 , 13 tomography 11 optical 12 coherence 12 coherence 13 tomography 13 tomography 15 oct 13 tomography 16 ) 14 ( 15 oct 15 oct 16 ) 17 and 20 markers 17 and 21 , 18 oxidative 20 markers 19 stress 20 markers 21 , 23 as 22 such 23 as 23 as 24 superoxide 23 as 46 ) 24 superoxide 26 dismutase 24 superoxide 34 substances 25 - 26 dismutase 26 dismutase 28 sod 26 dismutase 29 ) 27 ( 28 sod 28 sod 29 ) 30 , 34 substances 31 thiobarbituric 34 substances 32 acid 34 substances 33 reactive 34 substances 34 substances 36 tbars 34 substances 41 - 34 substances 46 ) 35 ( 36 tbars 36 tbars 37 ) 38 , 41 - 40 c 41 - 41 - 43 protein 41 - 46 ) 42 reactive 43 protein 43 protein 45 crp 44 ( 45 crp 45 crp 46 ) 47 from 49 samples 47 from 51 and 48 blood 49 samples 49 samples 50 before 51 and 52 after 52 after 53 treatment results : the oct showed that the macular edema in patients with severe disease was significantly reduced after treatment , while the cases with normal retinal thickness increased significantly ( p = 0.005 ) . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 35 . 2 : 4 oct 2 : 5 showed 3 the 4 oct 4 oct 5 showed 5 showed 6 that 6 that 9 edema 6 that 17 reduced 7 the 9 edema 8 macular 9 edema 9 edema 10 in 9 edema 15 was 10 in 11 patients 11 patients 12 with 12 with 14 disease 13 severe 14 disease 15 was 17 reduced 16 significantly 17 reduced 17 reduced 18 after 17 reduced 21 while 18 after 19 treatment 20 , 21 while 21 while 23 cases 21 while 28 increased 21 while 34 ) 22 the 23 cases 23 cases 24 with 23 cases 28 increased 24 with 27 thickness 25 normal 27 thickness 26 retinal 27 thickness 28 increased 29 significantly 28 increased 32 = 30 ( 32 = 31 p 32 = 32 = 33 0.005 32 = 34 ) comparing the mean values of sod , tbars and crp in the two groups , we found that they were significantly higher in the study group compared to controls ( p < 0.01 ) , being higher in patients with severe disease . 0 ###LEFT-WALL### 1 comparing 0 ###LEFT-WALL### 14 groups 0 ###LEFT-WALL### 15 , 1 comparing 4 values 1 comparing 14 groups 2 the 4 values 3 mean 4 values 4 values 5 of 5 of 10 crp 6 sod 8 tbars 7 , 8 tbars 8 tbars 9 and 9 and 10 crp 10 crp 11 in 11 in 13 two 12 the 13 two 15 , 16 we 15 , 17 found 16 we 17 found 17 found 18 that 18 that 19 they 18 that 20 were 19 they 20 were 20 were 21 significantly 20 were 22 higher 22 higher 23 in 22 higher 28 to 23 in 26 group 24 the 26 group 25 study 26 group 26 group 27 compared 28 to 29 controls 29 controls 32 < 29 controls 36 being 30 ( 32 < 31 p 32 < 32 < 33 0.01 32 < 34 ) 35 , 36 being 36 being 37 higher 36 being 43 . 37 higher 38 in 38 in 39 patients 39 patients 40 with 40 with 42 disease 41 severe 42 disease these values decreased post treatment , but they were still higher than in controls . 0 ###LEFT-WALL### 2 values 0 ###LEFT-WALL### 4 post 0 ###LEFT-WALL### 7 but 0 ###LEFT-WALL### 15 . 1 these 2 values 2 values 3 decreased 2 values 4 post 4 post 5 treatment 6 , 7 but 7 but 8 they 7 but 9 were 8 they 9 were 9 were 10 still 9 were 11 higher 11 higher 12 than 12 than 13 in 13 in 14 controls conclusions : the present research supports the role of oxidative stress and inflammation in amd and highlights the role of therapy directed against these risk factors . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 27 . 2 : 5 research 2 : 16 and 3 the 5 research 4 present 5 research 5 research 16 and 6 supports 12 and 6 supports 14 in 6 supports 16 and 7 the 8 role 8 role 9 of 8 role 12 and 9 of 11 stress 10 oxidative 11 stress 12 and 13 inflammation 14 in 15 amd 16 and 17 highlights 17 highlights 19 role 17 highlights 23 against 18 the 19 role 19 role 20 of 20 of 21 therapy 21 therapy 22 directed 23 against 26 factors 24 these 26 factors 25 risk 26 factors by monitoring the oxidative stress markers in the evolution of the disease , we showed that high values persist after treatment , thus supporting the idea that treatment should be followed for a long time . 0 ###LEFT-WALL### 14 we 0 ###LEFT-WALL### 15 showed 0 ###LEFT-WALL### 36 . 1 by 2 monitoring 1 by 13 , 1 by 14 we 2 monitoring 6 markers 2 monitoring 7 in 3 the 6 markers 4 oxidative 5 stress 5 stress 6 markers 7 in 9 evolution 8 the 9 evolution 9 evolution 10 of 10 of 12 disease 11 the 12 disease 14 we 15 showed 15 showed 17 high 15 showed 18 values 15 showed 31 followed 16 that 17 high 18 values 19 persist 19 persist 20 after 19 persist 23 thus 20 after 21 treatment 22 , 23 thus 23 thus 24 supporting 24 supporting 26 idea 24 supporting 30 be 25 the 26 idea 26 idea 27 that 27 that 28 treatment 27 that 29 should 28 treatment 29 should 30 be 31 followed 31 followed 32 for 32 for 35 time 33 a 34 long 33 a 35 time 34 long 35 time the process of aging induces the transformation of the face with changes that are usually classified as either chronological or photo - induced and that affect the shape , the texture , and the color of the face . 0 ###LEFT-WALL### 2 process 0 ###LEFT-WALL### 29 , 0 ###LEFT-WALL### 39 . 1 the 2 process 2 process 3 of 2 process 5 induces 3 of 4 aging 5 induces 7 transformation 6 the 7 transformation 7 transformation 8 of 8 of 10 face 9 the 10 face 10 face 11 with 10 face 16 classified 10 face 24 and 10 face 26 affect 11 with 12 changes 12 changes 13 that 12 changes 14 are 13 that 14 are 14 are 15 usually 16 classified 17 as 17 as 18 either 19 chronological 20 or 20 or 21 photo 20 or 22 - 20 or 23 induced 20 or 24 and 24 and 25 that 24 and 26 affect 26 affect 28 shape 27 the 28 shape 29 , 33 and 30 the 31 texture 31 texture 33 and 32 , 33 and 33 and 35 color 34 the 35 color 35 color 36 of 36 of 38 face 37 the 38 face facial shape is mainly transformed by the evolution of bones and soft tissues ( muscles , fat , and skin ) in addition to noticeable effects of gravity . 0 ###LEFT-WALL### 2 shape 0 ###LEFT-WALL### 5 transformed 0 ###LEFT-WALL### 29 . 1 facial 2 shape 2 shape 3 is 3 is 5 transformed 4 mainly 5 transformed 5 transformed 6 by 5 transformed 22 in 5 transformed 24 to 6 by 11 and 7 the 8 evolution 8 evolution 9 of 8 evolution 11 and 9 of 10 bones 11 and 13 tissues 11 and 19 and 12 soft 13 tissues 14 ( 19 and 15 muscles 16 , 16 , 17 fat 16 , 19 and 18 , 19 and 19 and 20 skin 19 and 21 ) 22 in 23 addition 24 to 26 effects 25 noticeable 26 effects 26 effects 27 of 27 of 28 gravity skin texture is mainly determined by wrinkles , which arise from atrophy of the skin layers , elastosis , and facial expressions . 0 ###LEFT-WALL### 2 texture 0 ###LEFT-WALL### 3 is 0 ###LEFT-WALL### 23 . 1 skin 2 texture 2 texture 3 is 3 is 4 mainly 3 is 22 expressions 5 determined 6 by 5 determined 20 and 6 by 7 wrinkles 7 wrinkles 9 which 7 wrinkles 18 elastosis 8 , 9 which 9 which 10 arise 9 which 17 , 10 arise 11 from 11 from 12 atrophy 12 atrophy 13 of 13 of 16 layers 14 the 16 layers 15 skin 16 layers 17 , 18 elastosis 18 elastosis 19 , 20 and 21 facial 20 and 22 expressions skin color is related to the distribution of skin chromophores and the structure of the dermis , which affects light scattering . 0 ###LEFT-WALL### 2 color 0 ###LEFT-WALL### 4 related 0 ###LEFT-WALL### 17 , 0 ###LEFT-WALL### 22 . 1 skin 2 color 2 color 3 is 3 is 4 related 4 related 5 to 5 to 11 and 6 the 7 distribution 7 distribution 8 of 7 distribution 11 and 8 of 10 chromophores 9 skin 10 chromophores 11 and 13 structure 12 the 13 structure 13 structure 14 of 14 of 16 dermis 15 the 16 dermis 17 , 18 which 17 , 19 affects 18 which 19 affects 19 affects 20 light 20 light 21 scattering all facial changes are [dependant] on sex , ethnicity , and lifestyle . 0 ###LEFT-WALL### 3 changes 0 ###LEFT-WALL### 4 are 0 ###LEFT-WALL### 13 . 1 all 3 changes 2 facial 3 changes 3 changes 4 are 4 are 6 on 6 on 11 and 7 sex 8 , 8 , 9 ethnicity 8 , 11 and 10 , 11 and 11 and 12 lifestyle they affect self [-] perception and social interactions and can sometimes be slowed down or reversed using appropriate clinical procedures ( eg , dermatological , surgical , cosmetic interventions ) . 0 ###LEFT-WALL### 1 they 0 ###LEFT-WALL### 2 affect 0 ###LEFT-WALL### 6 and 0 ###LEFT-WALL### 31 . 1 they 2 affect 2 affect 5 perception 3 self 5 perception 6 and 9 and 6 and 15 or 7 social 8 interactions 8 interactions 9 and 9 and 10 can 9 and 15 or 11 sometimes 12 be 12 be 13 slowed 12 be 15 or 13 slowed 14 down 15 or 16 reversed 15 or 17 using 17 using 20 procedures 18 appropriate 20 procedures 19 clinical 20 procedures 20 procedures 29 interventions 21 ( 29 interventions 22 eg 23 , 22 eg 29 interventions 24 dermatological 25 , 24 dermatological 29 interventions 26 surgical 27 , 26 surgical 29 interventions 28 cosmetic 29 interventions 29 interventions 30 ) although the effect of temporal pressure on spatio - temporal aspects of motor coordination and posture is well established in young adults , there is a clear lack of data on elderly subjects . 0 ###LEFT-WALL### 24 there 0 ###LEFT-WALL### 25 is 0 ###LEFT-WALL### 34 . 1 although 3 effect 1 although 17 is 1 although 23 , 1 although 24 there 2 the 3 effect 3 effect 4 of 3 effect 12 of 3 effect 17 is 4 of 6 pressure 5 temporal 6 pressure 6 pressure 7 on 7 on 11 aspects 8 spatio 9 - 8 spatio 11 aspects 10 temporal 11 aspects 12 of 15 and 13 motor 14 coordination 14 coordination 15 and 15 and 16 posture 17 is 18 well 18 well 19 established 19 established 20 in 20 in 22 adults 21 young 22 adults 24 there 25 is 25 is 28 lack 26 a 27 clear 26 a 28 lack 27 clear 28 lack 28 lack 29 of 29 of 30 data 30 data 31 on 31 on 33 subjects 32 elderly 33 subjects this work examined the aging - related effects of temporal pressure on movement synchronization and dynamic stability . 0 ###LEFT-WALL### 2 work 0 ###LEFT-WALL### 3 examined 0 ###LEFT-WALL### 7 related 1 this 2 work 2 work 3 examined 3 examined 5 aging 4 the 5 aging 6 - 7 related 7 related 8 effects 7 related 12 on 7 related 18 . 8 effects 9 of 9 of 11 pressure 10 temporal 11 pressure 12 on 15 and 13 movement 14 synchronization 14 synchronization 15 and 15 and 17 stability 16 dynamic 17 stability sixteen young and eleven elderly subjects performed series of simultaneous rapid leg flexions in an erect posture paired [with] ipsilateral index - finger extensions , minimizing the difference [between] heel and finger movement onsets . 0 ###LEFT-WALL### 31 and 0 ###LEFT-WALL### 35 . 1 sixteen 8 series 2 young 3 and 3 and 6 subjects 3 and 8 series 4 eleven 6 subjects 5 elderly 6 subjects 6 subjects 7 performed 8 series 9 of 8 series 31 and 9 of 13 flexions 10 simultaneous 12 leg 11 rapid 12 leg 12 leg 13 flexions 13 flexions 14 in 13 flexions 26 minimizing 14 in 21 index 15 an 16 erect 15 an 21 index 16 erect 21 index 17 posture 18 paired 18 paired 21 index 20 ipsilateral 21 index 21 index 24 extensions 22 - 24 extensions 23 finger 24 extensions 24 extensions 25 , 26 minimizing 30 heel 27 the 30 heel 28 difference 30 heel 31 and 34 onsets 32 finger 33 movement 33 movement 34 onsets this task was repeated ten times under two temporal conditions ( self [-] initiated [[] si ] vs [.] reaction - time [ rt ] ) . 0 ###LEFT-WALL### 2 task 0 ###LEFT-WALL### 4 repeated 0 ###LEFT-WALL### 27 . 1 this 2 task 2 task 3 was 3 was 4 repeated 4 repeated 6 times 5 ten 6 times 6 times 7 under 6 times 18 vs 7 under 10 conditions 8 two 10 conditions 9 temporal 10 conditions 10 conditions 16 si 11 ( 16 si 12 self 14 initiated 14 initiated 16 si 16 si 17 ] 18 vs 20 reaction 20 reaction 22 time 21 - 22 time 22 time 24 rt 22 time 26 ) 23 [ 24 rt 24 rt 25 ] results showed that , first , temporal pressure modified movement synchronization ; the finger extension preceded swing heel [-] off [in] rt , and [inversely] [in] si . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 showed 0 ###LEFT-WALL### 12 ; 0 ###LEFT-WALL### 28 . 1 results 2 showed 2 showed 3 that 3 that 8 pressure 3 that 9 modified 4 , 5 first 5 first 6 , 5 first 8 pressure 7 temporal 8 pressure 8 pressure 9 modified 9 modified 11 synchronization 10 movement 11 synchronization 12 ; 24 and 13 the 18 heel 14 finger 18 heel 15 extension 18 heel 16 preceded 17 swing 17 swing 18 heel 18 heel 20 off 18 heel 24 and 20 off 22 rt 23 , 24 and 24 and 27 si synchronization error and associated standard deviation were significantly greater in elderly than in young adults in si only , i.e . in the condition where proprioception is thought to be crucial for temporal coordination . 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 19 , 0 ###LEFT-WALL### 20 i.e 0 ###LEFT-WALL### 21 . 1 synchronization 2 error 2 error 3 and 3 and 5 standard 3 and 6 deviation 3 and 10 in 3 and 11 elderly 4 associated 5 standard 6 deviation 7 were 7 were 8 significantly 7 were 9 greater 9 greater 10 in 11 elderly 12 than 11 elderly 13 in 11 elderly 16 in 11 elderly 18 only 13 in 15 adults 14 young 15 adults 16 in 17 si 19 , 20 i.e 21 . 22 in 21 . 30 be 21 . 35 . 22 in 24 condition 22 in 30 be 23 the 24 condition 24 condition 25 where 24 condition 28 thought 25 where 26 proprioception 25 where 27 is 26 proprioception 27 is 28 thought 29 to 29 to 30 be 30 be 31 crucial 31 crucial 32 for 32 for 34 coordination 33 temporal 34 coordination secondly , both groups developed a significantly shorter mediolateral ( ml ) anticipatory postural adjustment duration in rt ( high temporal pressure ) than in si . 0 ###LEFT-WALL### 4 groups 0 ###LEFT-WALL### 5 developed 0 ###LEFT-WALL### 27 . 1 secondly 2 , 1 secondly 4 groups 3 both 4 groups 4 groups 5 developed 5 developed 16 duration 5 developed 17 in 5 developed 24 than 6 a 16 duration 7 significantly 8 shorter 8 shorter 15 adjustment 9 mediolateral 11 ml 9 mediolateral 15 adjustment 10 ( 11 ml 11 ml 12 ) 13 anticipatory 15 adjustment 14 postural 15 adjustment 15 adjustment 16 duration 17 in 18 rt 18 rt 22 pressure 19 ( 22 pressure 20 high 22 pressure 21 temporal 22 pressure 22 pressure 23 ) 24 than 25 in 25 in 26 si in both groups , this shortening was compensated by an increase in the anticipatory peak of centre - of [-] gravity ( cog ) [acceleration] towards the stance [-] leg [so] [that] ml dynamic stability at foot [-] [off] , quantified with the " extrapolated centre - of [-] mass ["] [,] [remained] unchanged [across] temporal conditions . 0 ###LEFT-WALL### 1 in 0 ###LEFT-WALL### 3 groups 0 ###LEFT-WALL### 4 , 1 in 3 groups 2 both 3 groups 4 , 6 shortening 4 , 8 compensated 5 this 6 shortening 6 shortening 7 was 7 was 8 compensated 8 compensated 9 by 8 compensated 12 in 9 by 11 increase 10 an 11 increase 12 in 15 peak 13 the 15 peak 14 anticipatory 15 peak 15 peak 16 of 15 peak 26 towards 16 of 17 centre 17 centre 19 of 18 - 19 of 19 of 21 gravity 19 of 24 ) 21 gravity 23 cog 22 ( 23 cog 23 cog 24 ) 26 towards 35 stability 27 the 35 stability 28 stance 35 stability 30 leg 35 stability 33 ml 35 stability 34 dynamic 35 stability 35 stability 36 at 36 at 37 foot 37 foot 41 quantified 37 foot 48 of 40 , 41 quantified 41 quantified 42 with 42 with 46 centre 43 the 44 " 43 the 46 centre 45 extrapolated 46 centre 47 - 48 of 48 of 57 conditions 48 of 58 . 50 mass 57 conditions 54 unchanged 57 conditions 56 temporal 57 conditions this increased cog acceleration was associated with an increased anticipatory peak of ml [centre] - of [-] pressure shift towards the swing [-] leg in young adults only . 0 ###LEFT-WALL### 4 acceleration 0 ###LEFT-WALL### 6 associated 0 ###LEFT-WALL### 15 - 1 this 2 increased 2 increased 4 acceleration 3 cog 4 acceleration 4 acceleration 5 was 5 was 6 associated 6 associated 7 with 7 with 11 peak 8 an 11 peak 9 increased 11 peak 10 anticipatory 11 peak 11 peak 12 of 12 of 13 ml 15 - 19 shift 15 - 29 . 16 of 18 pressure 16 of 19 shift 19 shift 20 towards 19 shift 25 in 19 shift 28 only 20 towards 24 leg 21 the 24 leg 22 swing 24 leg 25 in 27 adults 26 young 27 adults this suggested that the ability to accelerate the cog with the centre [-] of [-] pressure [shift] was degraded [in] elderly , probably due to weakness in the lower limb muscles . 0 ###LEFT-WALL### 1 this 0 ###LEFT-WALL### 2 suggested 0 ###LEFT-WALL### 32 . 1 this 2 suggested 2 suggested 3 that 3 that 5 ability 3 that 19 degraded 4 the 5 ability 5 ability 6 to 5 ability 7 accelerate 5 ability 18 was 6 to 7 accelerate 7 accelerate 9 cog 7 accelerate 10 with 8 the 9 cog 10 with 12 centre 11 the 12 centre 12 centre 14 of 14 of 16 pressure 18 was 19 degraded 19 degraded 22 , 21 elderly 22 , 22 , 23 probably 22 , 24 due 24 due 25 to 24 due 27 in 25 to 26 weakness 27 in 31 muscles 28 the 31 muscles 29 lower 30 limb 30 limb 31 muscles dynamic stability [at] foot - off was also degraded [in] elderly , [with] [a] consequent increased risk of ml imbalance and falling . 0 ###LEFT-WALL### 4 foot 0 ###LEFT-WALL### 5 - 1 dynamic 2 stability 2 stability 4 foot 5 - 6 off 5 - 7 was 5 - 23 . 6 off 7 was 7 was 17 risk 8 also 9 degraded 9 degraded 17 risk 11 elderly 12 , 11 elderly 17 risk 15 consequent 17 risk 16 increased 17 risk 17 risk 18 of 18 of 21 and 19 ml 20 imbalance 20 imbalance 21 and 21 and 22 falling the present study provides new insights into the ability of elderly adults to deal with temporal pressure constraints in adapting whole - body coordination of postural and focal components of paired movement . 0 ###LEFT-WALL### 3 study 0 ###LEFT-WALL### 4 provides 0 ###LEFT-WALL### 33 . 1 the 3 study 2 present 3 study 3 study 4 provides 4 provides 6 insights 4 provides 13 to 4 provides 19 in 5 new 6 insights 6 insights 7 into 6 insights 10 of 7 into 9 ability 8 the 9 ability 10 of 12 adults 11 elderly 12 adults 13 to 14 deal 14 deal 15 with 15 with 17 pressure 15 with 18 constraints 16 temporal 17 pressure 19 in 20 adapting 20 adapting 24 coordination 21 whole 22 - 21 whole 23 body 23 body 24 coordination 24 coordination 25 of 25 of 29 components 26 postural 27 and 27 and 28 focal 27 and 29 components 29 components 30 of 30 of 32 movement 31 paired 32 movement background : environmental and lifestyle factors regulate the expression and release of immune mediators . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 4 and 2 : 7 regulate 2 : 15 . 3 environmental 4 and 4 and 6 factors 4 and 7 regulate 5 lifestyle 6 factors 7 regulate 10 and 8 the 9 expression 9 expression 10 and 10 and 11 release 10 and 12 of 12 of 14 mediators 13 immune 14 mediators it has been hypothesised that ambient air pollution may be such an external factor and that the association between air pollution and impaired glucose metabolism may be attributable to inflammatory processes . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 4 hypothesised 0 ###LEFT-WALL### 32 . 1 it 2 has 2 has 3 been 3 been 4 hypothesised 4 hypothesised 15 and 5 that 8 pollution 5 that 10 be 5 that 15 and 6 ambient 7 air 7 air 8 pollution 8 pollution 9 may 9 may 10 be 10 be 14 factor 11 such 12 an 12 an 13 external 12 an 14 factor 13 external 14 factor 15 and 16 that 16 that 22 and 16 that 27 be 17 the 18 association 18 association 19 between 18 association 22 and 19 between 21 pollution 20 air 21 pollution 22 and 25 metabolism 22 and 26 may 23 impaired 24 glucose 24 glucose 25 metabolism 26 may 27 be 27 be 28 attributable 28 attributable 29 to 29 to 31 processes 30 inflammatory 31 processes therefore , we assessed the associations between air pollution , circulating immune mediators and impaired glucose metabolism . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 assessed 0 ###LEFT-WALL### 18 . 1 therefore 2 , 1 therefore 3 we 3 we 4 assessed 4 assessed 6 associations 4 assessed 7 between 5 the 6 associations 7 between 14 and 8 air 9 pollution 9 pollution 10 , 10 , 13 mediators 10 , 14 and 11 circulating 13 mediators 12 immune 13 mediators 14 and 17 metabolism 15 impaired 16 glucose 16 glucose 17 metabolism methods : we analysed concentrations of 14 [pro] - and anti - inflammatory immune mediators as well as fasting glucose and insulin levels in plasma of 363 women from the study on the influence of air pollution on lung function , inflammation and aging ( salia , germany ) . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 50 . 2 : 3 we 2 : 4 analysed 2 : 41 , 3 we 4 analysed 4 analysed 23 levels 4 analysed 40 function 5 concentrations 6 of 5 concentrations 10 and 6 of 7 14 9 - 10 and 10 and 15 mediators 10 and 23 levels 11 anti 12 - 11 anti 15 mediators 13 inflammatory 15 mediators 14 immune 15 mediators 15 mediators 18 as 16 as 17 well 17 well 18 as 18 as 21 and 19 fasting 20 glucose 20 glucose 21 and 21 and 22 insulin 23 levels 24 in 23 levels 26 of 23 levels 32 on 23 levels 40 function 24 in 25 plasma 26 of 28 women 27 363 28 women 28 women 29 from 29 from 31 study 30 the 31 study 32 on 34 influence 33 the 34 influence 34 influence 35 of 34 influence 38 on 35 of 37 pollution 36 air 37 pollution 38 on 39 lung 41 , 43 and 42 inflammation 43 and 43 and 44 aging 43 and 46 salia 45 ( 46 salia 46 salia 48 germany 46 salia 49 ) 47 , 48 germany 48 germany 49 ) exposure data for a group of pollutants such as nitrogen oxides ( no2 , nox ) and different fractions of particulate matter were available for the participants ' residences . 0 ###LEFT-WALL### 19 fractions 0 ###LEFT-WALL### 23 were 0 ###LEFT-WALL### 30 . 1 exposure 2 data 2 data 3 for 2 data 17 and 3 for 7 pollutants 4 a 5 group 5 group 6 of 5 group 7 pollutants 6 of 7 pollutants 7 pollutants 9 as 8 such 9 as 9 as 11 oxides 10 nitrogen 11 oxides 11 oxides 13 no2 12 ( 13 no2 13 no2 15 nox 13 no2 16 ) 14 , 15 nox 15 nox 16 ) 17 and 18 different 17 and 19 fractions 19 fractions 20 of 19 fractions 23 were 20 of 22 matter 21 particulate 22 matter 23 were 24 available 24 available 25 for 25 for 29 residences 26 the 27 participants 27 participants 28 ' 28 ' 29 residences we calculated the association between the pollutants and impaired glucose metabolism by multiple regression models . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 16 . 1 we 8 and 2 calculated 4 association 2 calculated 5 between 2 calculated 8 and 3 the 4 association 5 between 7 pollutants 6 the 7 pollutants 8 and 9 impaired 9 impaired 11 metabolism 9 impaired 12 by 10 glucose 11 metabolism 12 by 15 models 13 multiple 14 regression 14 regression 15 models results : the study participants had a mean age of 74.1 ( sd [2.6] ) [years] and 48 % showed impaired glucose metabolism based on impaired fasting glucose or previously diagnosed type 2 diabetes . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 35 . 2 : 5 participants 2 : 6 had 2 : 17 and 3 the 5 participants 4 study 5 participants 5 participants 6 had 6 had 9 age 7 a 9 age 8 mean 9 age 9 age 10 of 9 age 13 sd 10 of 11 74.1 12 ( 13 sd 13 sd 15 ) 17 and 19 % 17 and 20 showed 18 48 19 % 19 % 20 showed 20 showed 22 glucose 20 showed 23 metabolism 21 impaired 22 glucose 23 metabolism 24 based 23 metabolism 25 on 25 on 34 diabetes 26 impaired 34 diabetes 27 fasting 28 glucose 28 glucose 29 or 29 or 32 type 29 or 34 diabetes 30 previously 31 diagnosed 31 diagnosed 32 type 32 type 33 2 only long - term exposure no2 and nox concentrations showed positive associations ( no2 : or 1.465 , 95 % ci 1.049 - 2.046 , nox : or 1.409 , 95 % ci 1.010 - 1.967 ) [per] increased interquartile range of no2 ( 14.65 µg/m ( 3 ) ) or nox ( 43.16 µg/m ( 3 ) ) , respectively [,] but statistical significance [was] lost after correction for multiple comparisons . 0 ###LEFT-WALL### 2 long 0 ###LEFT-WALL### 3 - 1 only 2 long 3 - 4 term 3 - 15 : 4 term 6 no2 4 term 7 and 5 exposure 6 no2 7 and 8 nox 8 nox 9 concentrations 8 nox 10 showed 8 nox 14 no2 9 concentrations 10 showed 10 showed 12 associations 11 positive 12 associations 13 ( 14 no2 14 no2 15 : 15 : 16 or 15 : 25 , 16 or 17 1.465 16 or 23 - 18 , 23 - 19 95 21 ci 20 % 21 ci 21 ci 22 1.049 21 ci 23 - 23 - 24 2.046 23 - 25 , 25 , 26 nox 25 , 27 : 25 , 30 , 26 nox 27 : 27 : 28 or 28 or 29 1.409 30 , 33 ci 30 , 39 increased 31 95 33 ci 32 % 33 ci 33 ci 34 1.010 33 ci 36 1.967 33 ci 39 increased 35 - 36 1.967 36 1.967 37 ) 39 increased 51 or 40 interquartile 41 range 41 range 42 of 41 range 51 or 42 of 43 no2 43 no2 46 µg/m 44 ( 46 µg/m 45 14.65 46 µg/m 46 µg/m 48 3 46 µg/m 50 ) 47 ( 48 3 48 3 49 ) 51 or 52 nox 51 or 55 µg/m 51 or 63 but 53 ( 55 µg/m 54 43.16 55 µg/m 55 µg/m 57 3 55 µg/m 59 ) 56 ( 57 3 57 3 58 ) 60 , 61 respectively 60 , 63 but 63 but 65 significance 63 but 73 . 64 statistical 65 significance 65 significance 67 lost 65 significance 70 for 67 lost 68 after 68 after 69 correction 70 for 72 comparisons 71 multiple 72 comparisons additional adjustment for circulating immune mediators or the use of anti - inflammatory medication had [hardly] any impact on the observed ors . 0 ###LEFT-WALL### 7 or 0 ###LEFT-WALL### 15 had 0 ###LEFT-WALL### 23 . 1 additional 2 adjustment 2 adjustment 3 for 2 adjustment 7 or 3 for 4 circulating 4 circulating 6 mediators 5 immune 6 mediators 7 or 9 use 7 or 10 of 7 or 15 had 8 the 9 use 10 of 14 medication 11 anti 12 - 11 anti 14 medication 13 inflammatory 14 medication 15 had 18 impact 15 had 19 on 17 any 18 impact 19 on 22 ors 20 the 22 ors 21 observed 22 ors conclusions : our results suggest that exposure to nitrogen oxides may contribute to impaired glucose metabolism , but the associations did not reach statistical significance so that further studies with larger sample sizes are required to substantiate our findings . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 4 results 2 : 18 but 2 : 40 . 3 our 4 results 4 results 18 but 5 suggest 7 exposure 5 suggest 14 impaired 5 suggest 18 but 6 that 7 exposure 7 exposure 8 to 7 exposure 10 oxides 7 exposure 13 to 7 exposure 14 impaired 8 to 9 nitrogen 10 oxides 11 may 11 may 12 contribute 12 contribute 13 to 14 impaired 16 metabolism 15 glucose 16 metabolism 17 , 18 but 18 but 23 reach 19 the 20 associations 20 associations 21 did 21 did 22 not 21 did 23 reach 23 reach 25 significance 23 reach 27 that 23 reach 36 to 24 statistical 25 significance 26 so 27 that 27 that 29 studies 27 that 35 required 28 further 29 studies 29 studies 30 with 29 studies 34 are 30 with 33 sizes 31 larger 32 sample 32 sample 33 sizes 34 are 35 required 36 to 37 substantiate 37 substantiate 39 findings 38 our 39 findings our data do not preclude a role of inflammatory mechanisms in adipose or other tissues which may not be reflected by immune mediators in plasma . 0 ###LEFT-WALL### 2 data 0 ###LEFT-WALL### 5 preclude 0 ###LEFT-WALL### 20 reflected 1 our 2 data 2 data 3 do 3 do 4 not 3 do 5 preclude 5 preclude 7 role 5 preclude 11 in 6 a 7 role 7 role 8 of 8 of 10 mechanisms 9 inflammatory 10 mechanisms 11 in 13 or 12 adipose 13 or 13 or 14 other 15 tissues 16 which 15 tissues 17 may 15 tissues 20 reflected 16 which 17 may 17 may 18 not 17 may 19 be 20 reflected 21 by 20 reflected 24 in 20 reflected 26 . 21 by 23 mediators 22 immune 23 mediators 24 in 25 plasma objectives : medical homes [,] an important component of u.s . health reform , were first developed to help families of children with special health care needs ( cshcn ) find and coordinate services , and reduce their children 's unmet need for health services . 0 ###LEFT-WALL### 1 objectives 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 11 . 2 : 3 medical 2 : 4 homes 3 medical 4 homes 4 homes 8 component 6 an 8 component 7 important 8 component 8 component 9 of 9 of 10 u.s 11 . 13 reform 11 . 14 , 11 . 46 . 12 health 13 reform 14 , 32 and 15 were 17 developed 15 were 32 and 16 first 17 developed 17 developed 18 to 18 to 19 help 19 help 20 families 19 help 23 with 20 families 21 of 21 of 22 children 23 with 25 health 24 special 25 health 25 health 27 needs 25 health 31 find 26 care 27 needs 27 needs 29 cshcn 27 needs 31 find 28 ( 29 cshcn 29 cshcn 30 ) 32 and 36 and 33 coordinate 34 services 33 coordinate 36 and 35 , 36 and 36 and 37 reduce 37 reduce 42 need 37 reduce 43 for 38 their 39 children 39 children 40 's 40 's 42 need 41 unmet 42 need 43 for 45 services 44 health 45 services we hypothesize that cshcn lacking medical homes are more likely than those with medical homes to report health system delivery or coverage problems as the specific reasons for unmet need . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 hypothesize 0 ###LEFT-WALL### 11 than 0 ###LEFT-WALL### 31 . 1 we 2 hypothesize 2 hypothesize 3 that 3 that 4 cshcn 3 that 8 are 4 cshcn 5 lacking 4 cshcn 8 are 5 lacking 7 homes 6 medical 7 homes 8 are 9 more 8 are 10 likely 10 likely 11 than 11 than 21 or 11 than 30 need 12 those 13 with 12 those 16 to 12 those 21 or 13 with 15 homes 14 medical 15 homes 16 to 20 delivery 17 report 20 delivery 18 health 20 delivery 19 system 20 delivery 21 or 23 problems 21 or 24 as 21 or 28 for 21 or 30 need 22 coverage 23 problems 24 as 27 reasons 25 the 27 reasons 26 specific 27 reasons 28 for 29 unmet methods : data are from the 2005 - 2006 national survey of children with special health care needs ( ns - cshcn ) , a national , population - based survey of 40,723 cshcn . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 35 . 2 : 3 data 2 : 4 are 3 data 4 are 4 are 5 from 4 are 14 with 5 from 11 survey 6 the 8 - 7 2005 8 - 8 - 9 2006 8 - 11 survey 10 national 11 survey 11 survey 12 of 12 of 13 children 14 with 18 needs 14 with 31 survey 15 special 16 health 16 health 17 care 17 care 18 needs 18 needs 22 cshcn 19 ( 22 cshcn 20 ns 22 cshcn 21 - 22 cshcn 22 cshcn 23 ) 22 cshcn 24 , 25 a 26 national 25 a 31 survey 26 national 28 population 26 national 31 survey 27 , 28 population 28 population 29 - 30 based 31 survey 31 survey 32 of 32 of 34 cshcn 33 40,723 34 cshcn we studied whether lacking a medical home was associated with 9 specific reasons for unmet need for 11 types of medical services , controlling for health insurance , child 's health , and sociodemographic characteristics . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 studied 0 ###LEFT-WALL### 23 , 0 ###LEFT-WALL### 30 's 0 ###LEFT-WALL### 36 . 1 we 2 studied 2 studied 3 whether 3 whether 4 lacking 3 whether 16 need 4 lacking 7 home 4 lacking 8 was 5 a 7 home 6 medical 7 home 8 was 9 associated 9 associated 10 with 10 with 11 9 11 9 13 reasons 11 9 16 need 12 specific 13 reasons 13 reasons 14 for 13 reasons 16 need 14 for 15 unmet 16 need 17 for 17 for 20 of 18 11 20 of 19 types 20 of 20 of 22 services 21 medical 22 services 23 , 29 child 23 , 30 's 24 controlling 25 for 24 controlling 27 insurance 24 controlling 28 , 24 controlling 29 child 25 for 26 health 29 child 30 's 30 's 33 and 31 health 33 and 32 , 33 and 33 and 35 characteristics 34 sociodemographic 35 characteristics results : weighted to the national population , 17 % of cshcn reported at least one unmet health service need in the previous year . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 3 weighted 0 ###LEFT-WALL### 8 , 0 ###LEFT-WALL### 25 . 1 results 2 : 2 : 3 weighted 3 weighted 4 to 4 to 7 population 5 the 7 population 6 national 7 population 8 , 10 % 8 , 13 reported 9 17 10 % 10 % 11 of 10 % 13 reported 11 of 12 cshcn 13 reported 20 need 13 reported 21 in 14 at 15 least 15 least 16 one 16 one 20 need 17 unmet 18 health 18 health 20 need 19 service 20 need 21 in 24 year 22 the 24 year 23 previous 24 year cshcn without medical homes were 2 to 3 times as likely to report unmet need for child or family health services , and more likely to report no referral ( or= 3.3 ) , dissatisfaction with provider ( or=2.5 ) , service not available in area ( or= 2.1 ) , [can't] find provider who accepts insurance ( or=1.8 [ )(, and health plan problems ( or=1.4 [ )(as reasons for unmet need ( all p<0.05 ) . 1 cshcn 2 without 1 cshcn 5 were 2 without 4 homes 3 medical 4 homes 5 were 7 to 6 2 7 to 7 to 8 3 8 3 9 times 9 times 10 as 10 as 11 likely 11 likely 12 to 11 likely 18 or 12 to 15 need 13 report 15 need 14 unmet 15 need 15 need 16 for 16 for 17 child 18 or 21 services 18 or 22 , 18 or 23 and 19 family 21 services 20 health 21 services 22 , 23 and 23 and 25 likely 23 and 34 , 24 more 25 likely 25 likely 26 to 26 to 29 referral 27 report 29 referral 28 no 29 referral 29 referral 31 or= 30 ( 31 or= 31 or= 32 3.3 31 or= 33 ) 34 , 35 dissatisfaction 34 , 41 , 35 dissatisfaction 36 with 36 with 37 provider 37 provider 39 or=2.5 38 ( 39 or=2.5 39 or=2.5 40 ) 41 , 42 service 41 , 51 , 42 service 43 not 43 not 44 available 44 available 45 in 45 in 46 area 46 area 48 or= 47 ( 48 or= 48 or= 49 2.1 48 or= 50 ) 51 , 53 find 51 , 62 and 54 provider 55 who 54 provider 56 accepts 54 provider 59 or=1.8 55 who 56 accepts 56 accepts 57 insurance 58 ( 59 or=1.8 59 or=1.8 61 )(, 61 )(, 62 and 62 and 63 health 62 and 65 problems 64 plan 65 problems 65 problems 67 or=1.4 66 ( 67 or=1.4 67 or=1.4 69 )(as 67 or=1.4 78 . 69 )(as 70 reasons 70 reasons 71 for 70 reasons 76 p<0.05 71 for 73 need 72 unmet 73 need 74 ( 76 p<0.05 75 all 76 p<0.05 76 p<0.05 77 ) conclusions : cshcn without medical homes were more likely than those with medical homes to report health system delivery or coverage reasons for unmet child health service needs . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 3 cshcn 2 : 7 were 2 : 28 needs 2 : 29 . 3 cshcn 4 without 3 cshcn 7 were 4 without 6 homes 5 medical 6 homes 7 were 8 more 7 were 9 likely 9 likely 10 than 9 likely 15 to 9 likely 16 report 10 than 11 those 11 those 12 with 12 with 14 homes 13 medical 14 homes 15 to 16 report 16 report 22 reasons 17 health 18 system 18 system 22 reasons 19 delivery 20 or 20 or 21 coverage 20 or 22 reasons 22 reasons 23 for 22 reasons 27 service 22 reasons 28 needs 23 for 26 health 24 unmet 25 child 25 child 26 health 27 service 28 needs attributable risk estimates suggest that if the 50 % of cshcn who lacked medical homes had one , overall unmet need for child health services could be reduced by as much as 35 % and unmet need for family health services by 40 % . 0 ###LEFT-WALL### 3 estimates 0 ###LEFT-WALL### 4 suggest 0 ###LEFT-WALL### 18 , 0 ###LEFT-WALL### 45 . 1 attributable 3 estimates 2 risk 3 estimates 3 estimates 4 suggest 4 suggest 5 that 4 suggest 6 if 6 if 9 % 6 if 16 had 7 the 9 % 8 50 9 % 9 % 10 of 9 % 12 who 9 % 13 lacked 9 % 16 had 10 of 11 cshcn 12 who 13 lacked 13 lacked 15 homes 14 medical 15 homes 16 had 17 one 18 , 35 and 19 overall 20 unmet 20 unmet 21 need 21 need 22 for 21 need 28 reduced 21 need 35 and 22 for 23 child 23 child 25 services 23 child 27 be 24 health 25 services 25 services 26 could 26 could 27 be 28 reduced 29 by 29 by 34 % 30 as 31 much 31 much 32 as 32 as 33 35 33 35 34 % 35 and 37 need 35 and 38 for 35 and 40 health 35 and 41 services 36 unmet 37 need 38 for 39 family 40 health 41 services 41 services 42 by 42 by 44 % 43 40 44 % the accumulation of heteroplasmic mitochondrial dna ( mtdna ) deletions and single nucleotide variants ( snvs ) is a well [-] accepted facet of the biology of aging , yet comprehensive mutation spectra [have] not [been] described . 0 ###LEFT-WALL### 2 accumulation 0 ###LEFT-WALL### 18 is 0 ###LEFT-WALL### 38 . 1 the 2 accumulation 2 accumulation 3 of 2 accumulation 18 is 3 of 6 dna 4 heteroplasmic 6 dna 5 mitochondrial 6 dna 6 dna 11 and 7 ( 11 and 8 mtdna 9 ) 8 mtdna 10 deletions 10 deletions 11 and 11 and 14 variants 11 and 16 snvs 11 and 17 ) 12 single 13 nucleotide 13 nucleotide 14 variants 15 ( 16 snvs 16 snvs 17 ) 18 is 23 facet 19 a 23 facet 20 well 22 accepted 22 accepted 23 facet 23 facet 24 of 23 facet 27 of 24 of 26 biology 25 the 26 biology 27 of 33 spectra 28 aging 30 yet 29 , 30 yet 30 yet 31 comprehensive 30 yet 32 mutation 32 mutation 33 spectra 33 spectra 35 not 35 not 37 described to address this , we have used next generation sequencing of mtdna - enriched libraries ( mito - seq ) to investigate mtdna mutation spectra of putamen from young and aged donors . 0 ###LEFT-WALL### 1 to 0 ###LEFT-WALL### 4 , 0 ###LEFT-WALL### 33 . 1 to 4 , 2 address 3 this 2 address 4 , 4 , 22 investigate 5 we 6 have 6 have 7 used 7 used 8 next 7 used 10 sequencing 7 used 21 to 9 generation 10 sequencing 10 sequencing 11 of 10 sequencing 15 libraries 10 sequencing 19 seq 11 of 12 mtdna 13 - 15 libraries 14 enriched 15 libraries 15 libraries 17 mito 15 libraries 18 - 16 ( 17 mito 17 mito 18 - 18 - 19 seq 19 seq 20 ) 21 to 22 investigate 22 investigate 25 spectra 23 mtdna 24 mutation 24 mutation 25 spectra 25 spectra 26 of 26 of 27 putamen 27 putamen 28 from 28 from 32 donors 29 young 30 and 30 and 31 aged 30 and 32 donors frequencies of the " common " deletion and other " major arc " deletions were significantly increased in the aged cohort with the fold increase in the frequency of the common deletion exceeding that of major arc deletions . 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 17 increased 0 ###LEFT-WALL### 39 . 1 frequencies 2 of 1 frequencies 8 and 2 of 7 deletion 3 the 4 " 3 the 7 deletion 5 common 6 " 5 common 7 deletion 8 and 14 deletions 8 and 15 were 9 other 10 " 9 other 14 deletions 11 major 14 deletions 12 arc 13 " 12 arc 14 deletions 15 were 16 significantly 15 were 17 increased 17 increased 18 in 17 increased 22 with 17 increased 26 in 18 in 21 cohort 19 the 21 cohort 20 aged 21 cohort 22 with 25 increase 23 the 25 increase 24 fold 25 increase 26 in 28 frequency 27 the 28 frequency 28 frequency 29 of 29 of 32 deletion 30 the 32 deletion 31 common 32 deletion 32 deletion 33 exceeding 32 deletion 35 of 33 exceeding 34 that 35 of 38 deletions 36 major 37 arc 37 arc 38 deletions snvs also increased with age with the highest rate of accumulation in the [non] [-] coding control region which contains elements necessary for translation and replication . 0 ###LEFT-WALL### 25 and 0 ###LEFT-WALL### 27 . 1 snvs 3 increased 1 snvs 10 of 1 snvs 25 and 2 also 3 increased 3 increased 4 with 4 with 5 age 5 age 6 with 6 with 9 rate 7 the 8 highest 7 the 9 rate 10 of 11 accumulation 11 accumulation 12 in 11 accumulation 22 necessary 12 in 18 region 13 the 18 region 16 coding 17 control 17 control 18 region 18 region 19 which 18 region 20 contains 19 which 20 contains 20 contains 21 elements 22 necessary 23 for 23 for 24 translation 25 and 26 replication examination of predicted amino acid changes revealed [a] skew towards pathogenic snvs in the coding region driven by mutation bias . 0 ###LEFT-WALL### 6 changes 0 ###LEFT-WALL### 9 skew 0 ###LEFT-WALL### 21 . 1 examination 6 changes 2 of 5 acid 2 of 6 changes 3 predicted 5 acid 4 amino 5 acid 6 changes 7 revealed 6 changes 9 skew 9 skew 10 towards 9 skew 13 in 10 towards 12 snvs 11 pathogenic 12 snvs 13 in 16 region 14 the 16 region 15 coding 16 region 16 region 17 driven 17 driven 18 by 18 by 20 bias 19 mutation 20 bias levels of the pathogenic m.3243a>g trna mutation were also found to increase with age . 0 ###LEFT-WALL### 1 levels 0 ###LEFT-WALL### 10 found 0 ###LEFT-WALL### 15 . 1 levels 2 of 1 levels 8 were 2 of 7 mutation 3 the 7 mutation 4 pathogenic 7 mutation 5 m.3243a>g 7 mutation 6 trna 7 mutation 8 were 10 found 9 also 10 found 10 found 11 to 10 found 13 with 11 to 12 increase 13 with 14 age novel multimeric tandem duplications that resemble murine control region multimers and yeast ρ [(] - [ )(mtdnas , were identified in both young and aged specimens . 0 ###LEFT-WALL### 4 duplications 0 ###LEFT-WALL### 24 and 0 ###LEFT-WALL### 27 . 1 novel 3 tandem 2 multimeric 3 tandem 3 tandem 4 duplications 4 duplications 5 that 4 duplications 6 resemble 4 duplications 24 and 5 that 6 resemble 6 resemble 11 and 7 murine 10 multimers 8 control 10 multimers 9 region 10 multimers 10 multimers 11 and 11 and 13 ρ 11 and 15 - 11 and 17 )(mtdnas 12 yeast 13 ρ 15 - 17 )(mtdnas 17 )(mtdnas 18 , 19 were 20 identified 19 were 24 and 20 identified 21 in 20 identified 23 young 21 in 22 both 24 and 25 aged 24 and 26 specimens clonal ∼50 [bp] deletions in the control region were found at high frequencies in aged specimens . 0 ###LEFT-WALL### 4 deletions 0 ###LEFT-WALL### 10 found 0 ###LEFT-WALL### 17 . 1 clonal 4 deletions 2 ∼50 4 deletions 4 deletions 5 in 4 deletions 9 were 5 in 8 region 6 the 8 region 7 control 8 region 9 were 10 found 10 found 11 at 10 found 14 in 11 at 13 frequencies 12 high 13 frequencies 14 in 16 specimens 15 aged 16 specimens our results reveal the complex manner in which the mitochondrial genome alters with age and provides a foundation for studies of other tissues and disease states . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 15 and 0 ###LEFT-WALL### 27 . 1 our 2 results 2 results 15 and 3 reveal 6 manner 3 reveal 13 with 3 reveal 15 and 4 the 6 manner 5 complex 6 manner 6 manner 7 in 7 in 8 which 7 in 11 genome 7 in 12 alters 9 the 11 genome 10 mitochondrial 11 genome 11 genome 12 alters 13 with 14 age 15 and 16 provides 15 and 18 foundation 17 a 18 foundation 18 foundation 19 for 19 for 20 studies 20 studies 21 of 21 of 24 and 22 other 23 tissues 23 tissues 24 and 24 and 26 states 25 disease 26 states objective : while the prevalence of radiographic thumb carpometacarpal ( cmc1 ) osteoarthritis ( oa ) is well - described , little is known about clinically symptomatic disease presenting to physicians for care . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 34 . 2 : 22 little 2 : 24 known 3 while 5 prevalence 3 while 17 is 3 while 21 , 3 while 22 little 4 the 5 prevalence 5 prevalence 6 of 5 prevalence 17 is 6 of 13 osteoarthritis 7 radiographic 8 thumb 8 thumb 13 osteoarthritis 9 carpometacarpal 11 cmc1 9 carpometacarpal 13 osteoarthritis 10 ( 11 cmc1 11 cmc1 12 ) 13 osteoarthritis 15 oa 14 ( 15 oa 15 oa 16 ) 17 is 18 well 18 well 20 described 19 - 20 described 20 described 21 , 22 little 23 is 23 is 24 known 24 known 25 about 24 known 30 to 24 known 32 for 25 about 29 presenting 26 clinically 27 symptomatic 27 symptomatic 28 disease 28 disease 29 presenting 30 to 31 physicians 32 for 33 care we sought to determine the prevalence of doctor - diagnosed cmc1 oa . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 sought 0 ###LEFT-WALL### 9 - 0 ###LEFT-WALL### 13 . 1 we 2 sought 2 sought 3 to 2 sought 4 determine 3 to 4 determine 4 determine 6 prevalence 5 the 6 prevalence 6 prevalence 7 of 7 of 8 doctor 9 - 12 oa 10 diagnosed 12 oa 11 cmc1 12 oa methods : using health care data from skåne in southern sweden ( population 1.24 million ) , we identified all adults ages >20 years who consulted a physician at least once and received a diagnosis for cmc1 oa ( international classification of diseases , tenth revision , code m18 ) . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 18 we 2 : 19 identified 2 : 51 . 3 using 6 data 3 using 17 , 3 using 18 we 4 health 5 care 5 care 6 data 6 data 7 from 6 data 9 in 7 from 8 skåne 9 in 11 sweden 10 southern 11 sweden 11 sweden 13 population 12 ( 13 population 13 population 15 million 13 population 16 ) 14 1.24 15 million 18 we 19 identified 19 identified 21 adults 20 all 21 adults 21 adults 32 and 21 adults 36 for 22 ages 24 years 22 ages 32 and 23 >20 24 years 24 years 25 who 24 years 26 consulted 25 who 26 consulted 26 consulted 28 physician 26 consulted 30 least 26 consulted 31 once 27 a 28 physician 29 at 30 least 32 and 33 received 32 and 35 diagnosis 34 a 35 diagnosis 36 for 38 oa 37 cmc1 38 oa 38 oa 41 classification 39 ( 41 classification 40 international 41 classification 41 classification 42 of 41 classification 50 ) 42 of 43 diseases 43 diseases 46 revision 44 , 46 revision 45 tenth 46 revision 46 revision 49 m18 46 revision 50 ) 47 , 49 m18 48 code 49 m18 49 m18 50 ) data from the 15 - year period 1998 – 2012 were analyzed . 0 ###LEFT-WALL### 10 2012 0 ###LEFT-WALL### 12 analyzed 0 ###LEFT-WALL### 13 . 1 data 10 2012 2 from 4 15 2 from 10 2012 3 the 4 15 4 15 7 period 5 - 7 period 6 year 7 period 7 period 8 1998 7 period 9 – 10 2012 11 were 11 were 12 analyzed using cross - referencing with the swedish population register to exclude subjects who were deceased or had relocated , we obtained point estimates of the proportion of the population consulting for cmc1 oa . 0 ###LEFT-WALL### 2 cross 0 ###LEFT-WALL### 3 - 1 using 2 cross 3 - 20 we 3 - 21 obtained 4 referencing 5 with 4 referencing 12 subjects 4 referencing 19 , 4 referencing 20 we 5 with 9 register 6 the 9 register 7 swedish 8 population 8 population 9 register 9 register 10 to 9 register 11 exclude 10 to 11 exclude 12 subjects 13 who 12 subjects 14 were 13 who 14 were 14 were 16 or 15 deceased 16 or 16 or 17 had 17 had 18 relocated 20 we 21 obtained 21 obtained 23 estimates 22 point 23 estimates 23 estimates 24 of 23 estimates 27 of 24 of 26 proportion 25 the 26 proportion 27 of 29 population 28 the 29 population 29 population 30 consulting 29 population 31 for 31 for 33 oa 32 cmc1 33 oa 33 oa 34 . results : the prevalence of doctor - diagnosed cmc1 oa in adults was estimated at 1.4 % ( 2.2 % in women and 0.62 % in men ) . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 7 - 1 results 2 : 2 : 4 prevalence 3 the 4 prevalence 4 prevalence 5 of 5 of 6 doctor 7 - 10 oa 7 - 14 estimated 7 - 29 . 8 diagnosed 10 oa 9 cmc1 10 oa 10 oa 11 in 10 oa 13 was 11 in 12 adults 13 was 14 estimated 14 estimated 15 at 15 at 17 % 16 1.4 17 % 17 % 23 and 18 ( 23 and 19 2.2 21 in 20 % 21 in 21 in 22 women 22 women 23 and 23 and 27 men 23 and 28 ) 24 0.62 26 in 25 % 26 in 26 in 27 men the mean±sd age in the prevalent cmc1 cohort ( n=11,111 ) was 67.7±11.4 years ; 78.5 % of diagnoses were in women . 0 ###LEFT-WALL### 3 age 0 ###LEFT-WALL### 12 was 0 ###LEFT-WALL### 15 ; 0 ###LEFT-WALL### 23 . 1 the 3 age 2 mean±sd 3 age 3 age 4 in 3 age 12 was 4 in 8 cohort 5 the 8 cohort 6 prevalent 8 cohort 7 cmc1 8 cohort 8 cohort 10 n=11,111 9 ( 10 n=11,111 10 n=11,111 11 ) 12 was 14 years 13 67.7±11.4 14 years 15 ; 17 % 15 ; 20 were 16 78.5 17 % 17 % 18 of 17 % 20 were 18 of 19 diagnoses 20 were 21 in 21 in 22 women prevalence peaked in women ages 70 – 74 years with an estimate of 5.3 % and in men ages 80 – 84 years with an estimate of 1.7 % . 0 ###LEFT-WALL### 1 prevalence 0 ###LEFT-WALL### 2 peaked 0 ###LEFT-WALL### 21 – 0 ###LEFT-WALL### 30 . 1 prevalence 2 peaked 2 peaked 3 in 3 in 4 women 4 women 5 ages 4 women 9 years 5 ages 6 70 7 – 9 years 8 74 9 years 9 years 16 and 9 years 21 – 10 with 12 estimate 10 with 16 and 11 an 12 estimate 12 estimate 13 of 13 of 15 % 14 5.3 15 % 16 and 17 in 17 in 18 men 18 men 19 ages 19 ages 20 80 21 – 23 years 22 84 23 years 23 years 24 with 24 with 26 estimate 25 an 26 estimate 26 estimate 27 of 27 of 29 % 28 1.7 29 % age at initial diagnosis also differed , with women presenting between ages 60 – 69 years and men presenting between ages 70 – 79 years . 0 ###LEFT-WALL### 1 age 0 ###LEFT-WALL### 6 differed 1 age 2 at 1 age 6 differed 2 at 4 diagnosis 3 initial 4 diagnosis 5 also 6 differed 6 differed 8 with 7 , 8 with 8 with 9 women 8 with 26 . 9 women 10 presenting 10 presenting 11 between 10 presenting 25 years 11 between 12 ages 12 ages 13 60 12 ages 17 and 14 – 17 and 15 69 16 years 16 years 17 and 17 and 18 men 17 and 19 presenting 17 and 23 – 19 presenting 20 between 19 presenting 22 70 20 between 21 ages 24 79 25 years conclusion : the clinically important prevalence of cmc1 oa is 3 to 4 times higher in women than men . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 6 prevalence 2 : 10 is 2 : 20 . 3 the 6 prevalence 4 clinically 5 important 5 important 6 prevalence 6 prevalence 7 of 6 prevalence 10 is 7 of 9 oa 8 cmc1 9 oa 10 is 14 times 11 3 12 to 12 to 13 4 12 to 14 times 14 times 15 higher 15 higher 16 in 15 higher 18 than 16 in 17 women 18 than 19 men by the end of2012 , more than 1 in 20 elderly women had consulted a physician for cmc1 oa over the last 15 years . 0 ###LEFT-WALL### 8 1 0 ###LEFT-WALL### 14 consulted 0 ###LEFT-WALL### 25 . 1 by 4 of2012 1 by 5 , 1 by 8 1 2 the 4 of2012 3 end 4 of2012 6 more 7 than 7 than 8 1 8 1 9 in 8 1 13 had 9 in 12 women 10 20 12 women 11 elderly 12 women 13 had 14 consulted 14 consulted 16 physician 14 consulted 17 for 14 consulted 20 over 15 a 16 physician 17 for 19 oa 18 cmc1 19 oa 20 over 24 years 21 the 22 last 21 the 23 15 23 15 24 years the high prevalence of this subset of hand oa is a concern in an aging population . 0 ###LEFT-WALL### 3 prevalence 0 ###LEFT-WALL### 10 is 0 ###LEFT-WALL### 17 . 1 the 3 prevalence 2 high 3 prevalence 3 prevalence 4 of 3 prevalence 10 is 4 of 6 subset 5 this 6 subset 6 subset 7 of 7 of 9 oa 8 hand 9 oa 10 is 12 concern 11 a 12 concern 12 concern 13 in 13 in 16 population 14 an 16 population 15 aging 16 population objective : there is evidence to suggest that older adults are underrepresented in randomized controlled trials of health interventions . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 2 : 3 there 2 : 4 is 2 : 20 . 3 there 4 is 4 is 5 evidence 4 is 6 to 6 to 7 suggest 7 suggest 8 that 8 that 10 adults 8 that 11 are 9 older 10 adults 10 adults 11 are 11 are 12 underrepresented 12 underrepresented 13 in 13 in 16 trials 14 randomized 16 trials 15 controlled 16 trials 16 trials 17 of 17 of 19 interventions 18 health 19 interventions the aim of this review was to systematically examine the age - related inclusion criteria distribution of participants in randomized controlled trials ( rcts ) of low back pain ( lbp ) [interventions] [and] to investigate if this distribution pattern changes over time . 0 ###LEFT-WALL### 2 aim 0 ###LEFT-WALL### 13 related 0 ###LEFT-WALL### 44 . 1 the 2 aim 2 aim 3 of 2 aim 6 was 3 of 5 review 4 this 5 review 6 was 7 to 6 was 9 examine 7 to 9 examine 8 systematically 9 examine 9 examine 11 age 10 the 11 age 12 - 13 related 13 related 16 distribution 13 related 35 to 14 inclusion 16 distribution 15 criteria 16 distribution 16 distribution 17 of 17 of 18 participants 18 participants 19 in 18 participants 26 of 18 participants 31 lbp 19 in 22 trials 20 randomized 22 trials 21 controlled 22 trials 22 trials 24 rcts 23 ( 24 rcts 24 rcts 25 ) 26 of 29 pain 27 low 28 back 28 back 29 pain 30 ( 31 lbp 31 lbp 32 ) 35 to 36 investigate 36 investigate 37 if 37 if 40 pattern 37 if 41 changes 38 this 40 pattern 39 distribution 40 pattern 40 pattern 41 changes 41 changes 42 over 42 over 43 time methods : we identified , in pubmed , 1,047 rcts on nonspecific lbp published since 1992 , of which a random sample of 400 was assessed for inclusion in the review . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 32 . 2 : 3 we 2 : 4 identified 2 : 17 , 3 we 4 identified 4 identified 6 in 4 identified 10 rcts 5 , 6 in 6 in 7 pubmed 6 in 8 , 9 1,047 10 rcts 10 rcts 11 on 11 on 13 lbp 12 nonspecific 13 lbp 13 lbp 14 published 13 lbp 15 since 15 since 16 1992 17 , 22 sample 17 , 26 assessed 18 of 19 which 18 of 22 sample 20 a 21 random 20 a 22 sample 21 random 22 sample 22 sample 23 of 22 sample 25 was 23 of 24 400 25 was 26 assessed 26 assessed 27 for 26 assessed 29 in 27 for 28 inclusion 29 in 31 review 30 the 31 review included studies [were] grouped according to treatment type . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 8 type 0 ###LEFT-WALL### 9 . 1 included 2 studies 2 studies 4 grouped 2 studies 8 type 4 grouped 6 to 5 according 6 to 6 to 7 treatment data were extracted on year [of] publication [,] types of treatment , total number of participants , age inclusion criteria , and age of included participants . 0 ###LEFT-WALL### 1 data 0 ###LEFT-WALL### 3 extracted 0 ###LEFT-WALL### 27 . 1 data 2 were 2 were 3 extracted 3 extracted 4 on 4 on 9 types 5 year 9 types 7 publication 9 types 9 types 10 of 10 of 22 and 11 treatment 12 , 12 , 14 number 12 , 22 and 13 total 14 number 14 number 15 of 15 of 16 participants 16 participants 20 criteria 17 , 20 criteria 18 age 20 criteria 19 inclusion 20 criteria 20 criteria 21 , 21 , 22 and 22 and 23 age 22 and 24 of 24 of 26 participants 25 included 26 participants results : a total of 274 rcts published between 1992 and 2010 met the inclusion criteria . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 4 total 2 : 13 met 2 : 17 . 3 a 4 total 4 total 5 of 4 total 8 published 4 total 13 met 5 of 7 rcts 6 274 7 rcts 8 published 9 between 9 between 11 and 10 1992 11 and 11 and 12 2010 13 met 16 criteria 14 the 16 criteria 15 inclusion 16 criteria a total of 41.6 % ( n = 114 ) of the included trials excluded people ages >65 years . 0 ###LEFT-WALL### 2 total 0 ###LEFT-WALL### 15 excluded 0 ###LEFT-WALL### 20 . 1 a 2 total 2 total 3 of 2 total 11 of 2 total 15 excluded 3 of 5 % 4 41.6 5 % 5 % 8 = 6 ( 8 = 7 n 8 = 8 = 9 114 8 = 10 ) 11 of 14 trials 12 the 14 trials 13 included 14 trials 15 excluded 19 years 16 people 19 years 17 ages 19 years 18 >65 19 years the pooled mean age of participants was 44.3 years ( 95 % confidence interval 42.4 - 46.3 ) ; the pooled minimum age for inclusion was 19.8 years and the pooled maximum age for inclusion was 65.4 years . 0 ###LEFT-WALL### 4 age 0 ###LEFT-WALL### 7 was 0 ###LEFT-WALL### 19 ; 0 ###LEFT-WALL### 39 . 1 the 4 age 2 pooled 4 age 3 mean 4 age 4 age 5 of 4 age 7 was 5 of 6 participants 7 was 9 years 8 44.3 9 years 9 years 14 interval 10 ( 14 interval 11 95 12 % 12 % 14 interval 13 confidence 14 interval 14 interval 15 42.4 14 interval 17 46.3 14 interval 19 ; 16 - 17 46.3 17 46.3 18 ) 19 ; 23 age 19 ; 26 was 19 ; 29 and 20 the 23 age 21 pooled 23 age 22 minimum 23 age 23 age 24 for 23 age 26 was 24 for 25 inclusion 26 was 28 years 27 19.8 28 years 29 and 33 age 29 and 36 was 30 the 33 age 31 pooled 33 age 32 maximum 33 age 33 age 34 for 33 age 36 was 34 for 35 inclusion 36 was 38 years 37 65.4 38 years we found no trend of including older participants in rcts on lbp over time . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 found 0 ###LEFT-WALL### 15 . 1 we 2 found 2 found 4 trend 3 no 4 trend 4 trend 5 of 5 of 6 including 6 including 8 participants 6 including 9 in 6 including 11 on 6 including 13 over 7 older 8 participants 9 in 10 rcts 11 on 12 lbp 13 over 14 time conclusion : despite an aging population around the globe , older adults are largely excluded from rcts evaluating management of lbp , and there is no evidence of change in this practice over the last 2 decades . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 12 adults 2 : 15 excluded 2 : 23 and 2 : 38 . 3 despite 6 population 3 despite 12 adults 4 an 6 population 5 aging 6 population 7 around 9 globe 7 around 10 , 7 around 12 adults 8 the 9 globe 11 older 12 adults 12 adults 13 are 13 are 15 excluded 14 largely 15 excluded 15 excluded 16 from 16 from 19 management 17 rcts 19 management 18 evaluating 19 management 19 management 20 of 20 of 21 lbp 22 , 23 and 23 and 24 there 23 and 25 is 24 there 25 is 25 is 27 evidence 26 no 27 evidence 27 evidence 28 of 27 evidence 30 in 28 of 29 change 30 in 32 practice 31 this 32 practice 32 practice 33 over 33 over 37 decades 34 the 35 last 34 the 36 2 36 2 37 decades in the past few years , there has been an increasing awareness of the regional vulnerability of the hippocampus to age - related processes . 0 ###LEFT-WALL### 7 there 0 ###LEFT-WALL### 9 been 0 ###LEFT-WALL### 23 related 0 ###LEFT-WALL### 25 . 1 in 5 years 1 in 6 , 1 in 7 there 2 the 3 past 2 the 4 few 4 few 5 years 7 there 8 has 8 has 9 been 9 been 12 awareness 10 an 12 awareness 11 increasing 12 awareness 12 awareness 13 of 13 of 16 vulnerability 14 the 16 vulnerability 15 regional 16 vulnerability 16 vulnerability 17 of 16 vulnerability 20 to 16 vulnerability 21 age 17 of 19 hippocampus 18 the 19 hippocampus 20 to 21 age 22 - 23 related 23 related 24 processes however , to date , no studies have assessed the effects of age on different structural magnetic resonance parameters in the specific hippocampal subfields . 0 ###LEFT-WALL### 7 studies 0 ###LEFT-WALL### 9 assessed 0 ###LEFT-WALL### 25 . 1 however 2 , 1 however 7 studies 2 , 4 date 3 to 4 date 4 date 5 , 4 date 7 studies 6 no 7 studies 7 studies 8 have 8 have 9 assessed 9 assessed 11 effects 9 assessed 14 on 9 assessed 20 in 10 the 11 effects 11 effects 12 of 12 of 13 age 14 on 19 parameters 15 different 18 resonance 16 structural 18 resonance 17 magnetic 18 resonance 18 resonance 19 parameters 20 in 24 subfields 21 the 24 subfields 22 specific 24 subfields 23 hippocampal 24 subfields in this study , we measured volume , mean diffusivity ( md [ )(and fractional anisotropy ( fa ) in the presubiculum , subiculum , fimbria , cornu ammonis ( ca ) 1,2 - 3,4 - dg and the whole hippocampus in fifty cognitively intact elder adults between 50 and 75 years of age ( 20 men , 30 women ) . 0 ###LEFT-WALL### 5 we 0 ###LEFT-WALL### 6 measured 0 ###LEFT-WALL### 8 , 0 ###LEFT-WALL### 62 . 1 in 3 study 1 in 4 , 1 in 5 we 2 this 3 study 5 we 6 measured 6 measured 7 volume 8 , 9 mean 8 , 27 , 9 mean 10 diffusivity 9 mean 20 in 10 diffusivity 14 )(and 11 ( 14 )(and 12 md 14 )(and 14 )(and 16 anisotropy 14 )(and 18 fa 14 )(and 19 ) 15 fractional 16 anisotropy 17 ( 18 fa 18 fa 19 ) 20 in 22 presubiculum 21 the 22 presubiculum 22 presubiculum 24 subiculum 22 presubiculum 26 fimbria 23 , 24 subiculum 24 subiculum 25 , 25 , 26 fimbria 26 fimbria 27 , 27 , 28 cornu 27 , 36 - 28 cornu 29 ammonis 28 cornu 34 - 29 ammonis 31 ca 30 ( 31 ca 31 ca 32 ) 33 1,2 34 - 34 - 35 3,4 36 - 38 and 37 dg 38 and 38 and 41 hippocampus 38 and 42 in 38 and 48 between 38 and 53 of 39 the 41 hippocampus 40 whole 41 hippocampus 42 in 47 adults 43 fifty 47 adults 44 cognitively 45 intact 45 intact 47 adults 46 elder 47 adults 48 between 52 years 49 50 50 and 50 and 51 75 50 and 52 years 53 of 54 age 54 age 57 men 54 age 60 women 55 ( 57 men 56 20 57 men 57 men 58 , 58 , 60 women 59 30 60 women 60 women 61 ) segmentation of hippocampal subfields was performed using freesurfer . 0 ###LEFT-WALL### 1 segmentation 0 ###LEFT-WALL### 6 performed 0 ###LEFT-WALL### 9 . 1 segmentation 2 of 1 segmentation 5 was 2 of 4 subfields 3 hippocampal 4 subfields 5 was 6 performed 6 performed 7 using 7 using 8 freesurfer individual md and fa images were coregistered to t1 - weighted volumes using flirt of fsl . 0 ###LEFT-WALL### 5 images 0 ###LEFT-WALL### 7 coregistered 1 individual 2 md 2 md 3 and 3 and 4 fa 4 fa 5 images 5 images 6 were 6 were 7 coregistered 7 coregistered 8 to 8 to 9 t1 9 t1 12 volumes 10 - 12 volumes 11 weighted 12 volumes 12 volumes 13 using 12 volumes 17 . 13 using 14 flirt 14 flirt 15 of 15 of 16 fsl linear regression analyses were performed to assess the effects of age on the anatomical measures of each subfield . 0 ###LEFT-WALL### 3 analyses 0 ###LEFT-WALL### 5 performed 0 ###LEFT-WALL### 19 . 1 linear 3 analyses 2 regression 3 analyses 3 analyses 4 were 4 were 5 performed 5 performed 6 to 5 performed 12 on 6 to 7 assess 7 assess 9 effects 8 the 9 effects 9 effects 10 of 10 of 11 age 12 on 15 measures 13 the 15 measures 14 anatomical 15 measures 15 measures 16 of 16 of 18 subfield 17 each 18 subfield in addition , multiple regression analyses were also carried out to assess which of the anatomical measures that showed a correlation with age in the previous analyses , were the best age predictors in the hippocampus . 0 ###LEFT-WALL### 6 analyses 0 ###LEFT-WALL### 9 carried 0 ###LEFT-WALL### 37 . 1 in 2 addition 1 in 3 , 1 in 6 analyses 4 multiple 6 analyses 5 regression 6 analyses 6 analyses 7 were 7 were 9 carried 8 also 9 carried 9 carried 10 out 9 carried 11 to 11 to 12 assess 12 assess 13 which 12 assess 34 in 13 which 14 of 13 which 18 that 13 which 28 , 14 of 17 measures 15 the 17 measures 16 anatomical 17 measures 18 that 28 , 19 showed 21 correlation 19 showed 28 , 20 a 21 correlation 21 correlation 22 with 22 with 23 age 23 age 24 in 24 in 27 analyses 25 the 26 previous 25 the 27 analyses 28 , 29 were 29 were 33 predictors 30 the 31 best 30 the 33 predictors 32 age 33 predictors 34 in 36 hippocampus 35 the 36 hippocampus in agreement with previous studies , our results showed a significant association between age and volume ( p < 0.001 ) as well as md ( p < 0.001 ) in the whole hippocampus . 0 ###LEFT-WALL### 8 results 0 ###LEFT-WALL### 9 showed 0 ###LEFT-WALL### 35 . 1 in 2 agreement 1 in 6 , 1 in 8 results 2 agreement 3 with 3 with 5 studies 4 previous 5 studies 7 our 8 results 8 results 9 showed 9 showed 12 association 9 showed 31 in 10 a 11 significant 10 a 12 association 11 significant 12 association 12 association 13 between 12 association 24 as 13 between 15 and 14 age 15 and 15 and 16 volume 15 and 19 < 17 ( 19 < 18 p 19 < 19 < 20 0.001 19 < 21 ) 22 as 23 well 23 well 24 as 24 as 25 md 25 md 28 < 26 ( 28 < 27 p 28 < 28 < 29 0.001 28 < 30 ) 31 in 34 hippocampus 32 the 34 hippocampus 33 whole 34 hippocampus regarding the specific hippocampal subfields , we found that age had a significant negative effect on volume in ca2 - 3 ( p < 0.001 ) and ca4 - dg ( p < 0.001 ) . 0 ###LEFT-WALL### 7 we 0 ###LEFT-WALL### 8 found 0 ###LEFT-WALL### 36 . 1 regarding 5 subfields 1 regarding 6 , 1 regarding 7 we 2 the 5 subfields 3 specific 5 subfields 4 hippocampal 5 subfields 7 we 8 found 8 found 9 that 9 that 10 age 9 that 11 had 10 age 11 had 11 had 15 effect 11 had 18 in 11 had 33 < 12 a 15 effect 13 significant 14 negative 14 negative 15 effect 15 effect 16 on 16 on 17 volume 18 in 27 and 19 ca2 21 3 19 ca2 27 and 20 - 21 3 21 3 24 < 21 3 26 ) 22 ( 24 < 23 p 24 < 24 < 25 0.001 24 < 26 ) 27 and 30 dg 28 ca4 30 dg 29 - 30 dg 31 ( 33 < 32 p 33 < 33 < 34 0.001 33 < 35 ) importantly , we found a positive effect of age on md in ca2 - 3 ( p < 0.001 ) and fimbria ( p < 0.001 ) as well as a negative age effect on fa in the subiculum ( p < 0.001 ) . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 found 0 ###LEFT-WALL### 45 . 1 importantly 2 , 1 importantly 3 we 3 we 4 found 4 found 7 effect 4 found 10 on 4 found 12 in 4 found 25 < 4 found 29 well 4 found 30 as 5 a 7 effect 6 positive 7 effect 7 effect 8 of 8 of 9 age 10 on 11 md 12 in 21 and 13 ca2 15 3 13 ca2 21 and 14 - 15 3 15 3 18 < 15 3 20 ) 16 ( 18 < 17 p 18 < 18 < 19 0.001 18 < 20 ) 21 and 22 fimbria 23 ( 25 < 24 p 25 < 25 < 26 0.001 25 < 27 ) 28 as 29 well 30 as 34 effect 30 as 35 on 31 a 32 negative 31 a 34 effect 32 negative 33 age 33 age 34 effect 35 on 36 fa 36 fa 37 in 36 fa 42 < 37 in 39 subiculum 38 the 39 subiculum 40 ( 42 < 41 p 42 < 42 < 43 0.001 42 < 44 ) multiple regression analyses revealed that the best overall predictors of age in the hippocampus were md in the fimbria and volume of ca2 - 3 , which explained 73.8 % of the age variance . 0 ###LEFT-WALL### 3 analyses 0 ###LEFT-WALL### 4 revealed 0 ###LEFT-WALL### 35 . 1 multiple 3 analyses 2 regression 3 analyses 3 analyses 4 revealed 4 revealed 5 that 5 that 9 predictors 5 that 15 were 6 the 7 best 6 the 9 predictors 8 overall 9 predictors 9 predictors 10 of 9 predictors 15 were 10 of 11 age 11 age 12 in 12 in 14 hippocampus 13 the 14 hippocampus 15 were 16 md 15 were 17 in 17 in 20 and 18 the 19 fimbria 19 fimbria 20 and 20 and 21 volume 20 and 22 of 20 and 27 which 20 and 28 explained 22 of 23 ca2 23 ca2 25 3 24 - 25 3 25 3 26 , 27 which 28 explained 28 explained 30 % 29 73.8 30 % 30 % 31 of 31 of 34 variance 32 the 34 variance 33 age 34 variance these results indicate that age has an effect both on volume and diffusion tensor imaging measures in different subfields , suggesting they provide complementary information on age - related processes in the hippocampus . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 indicate 0 ###LEFT-WALL### 29 related 0 ###LEFT-WALL### 34 . 1 these 2 results 2 results 3 indicate 3 indicate 4 that 4 that 5 age 4 that 6 has 5 age 6 has 6 has 8 effect 7 an 8 effect 8 effect 15 imaging 8 effect 16 measures 8 effect 21 suggesting 9 both 10 on 9 both 12 and 10 on 11 volume 12 and 13 diffusion 12 and 15 imaging 14 tensor 15 imaging 15 imaging 16 measures 16 measures 17 in 17 in 19 subfields 18 different 19 subfields 20 , 21 suggesting 21 suggesting 22 they 21 suggesting 23 provide 21 suggesting 28 - 23 provide 25 information 24 complementary 25 information 25 information 26 on 26 on 27 age 28 - 29 related 29 related 30 processes 29 related 31 in 31 in 33 hippocampus 32 the 33 hippocampus [non] - linear optical microscopy is becoming popular as a [non] [-] invasive in [vivo] imaging modality [in] dermatology . 0 ###LEFT-WALL### 2 - 0 ###LEFT-WALL### 6 is 0 ###LEFT-WALL### 20 . 2 - 5 microscopy 3 linear 5 microscopy 4 optical 5 microscopy 5 microscopy 6 is 6 is 7 becoming 7 becoming 8 popular 8 popular 9 as 9 as 19 dermatology 10 a 14 in 13 invasive 14 in 14 in 19 dermatology 16 imaging 19 dermatology 17 modality 19 dermatology in this study , combined tpf and shg microscopy were used to monitor collagen remodelling in vivo after micro - ablative fractional laser resurfacing . 0 ###LEFT-WALL### 7 and 0 ###LEFT-WALL### 11 used 0 ###LEFT-WALL### 25 . 1 in 3 study 1 in 4 , 1 in 7 and 2 this 3 study 5 combined 6 tpf 6 tpf 7 and 7 and 9 microscopy 7 and 10 were 8 shg 9 microscopy 10 were 11 used 11 used 12 to 11 used 13 monitor 12 to 13 monitor 13 monitor 15 remodelling 13 monitor 17 vivo 13 monitor 18 after 14 collagen 15 remodelling 16 in 17 vivo 18 after 24 resurfacing 19 micro 20 - 19 micro 23 laser 21 ablative 23 laser 22 fractional 23 laser 23 laser 24 resurfacing papillary [dermis] of living subjects , covering a wide age range , was imaged immediately before and forty days after treatment . 0 ###LEFT-WALL### 1 papillary 0 ###LEFT-WALL### 14 imaged 0 ###LEFT-WALL### 22 . 1 papillary 3 of 1 papillary 13 was 3 of 5 subjects 4 living 5 subjects 5 subjects 7 covering 6 , 7 covering 7 covering 11 range 7 covering 12 , 8 a 9 wide 8 a 11 range 9 wide 10 age 10 age 11 range 13 was 14 imaged 14 imaged 17 and 15 immediately 16 before 16 before 17 and 17 and 20 after 18 forty 19 days 19 days 20 after 20 after 21 treatment a qualitative visual examination of acquired images demonstrated an age - dependent remodelling effect on collagen . 0 ###LEFT-WALL### 4 examination 0 ###LEFT-WALL### 8 demonstrated 0 ###LEFT-WALL### 11 - 0 ###LEFT-WALL### 17 . 1 a 2 qualitative 1 a 4 examination 2 qualitative 4 examination 3 visual 4 examination 4 examination 5 of 4 examination 8 demonstrated 5 of 7 images 6 acquired 7 images 8 demonstrated 10 age 9 an 10 age 11 - 14 effect 12 dependent 14 effect 13 remodelling 14 effect 14 effect 15 on 15 on 16 collagen additional quantitative analysis of new collagen production was performed by means of two image analysis methods . 0 ###LEFT-WALL### 3 analysis 0 ###LEFT-WALL### 9 performed 0 ###LEFT-WALL### 17 . 1 additional 3 analysis 2 quantitative 3 analysis 3 analysis 4 of 3 analysis 8 was 4 of 7 production 5 new 7 production 6 collagen 7 production 8 was 9 performed 9 performed 10 by 10 by 11 means 11 means 12 of 12 of 16 methods 13 two 16 methods 14 image 16 methods 15 analysis 16 methods a higher increase in shg to tpf [ratio] , corresponding to a stronger treatment [effectiveness] , was found in older subjects , whereas the effect was found to be negligible in young , and minimal in middle age subjects . 0 ###LEFT-WALL### 3 increase 0 ###LEFT-WALL### 29 be 0 ###LEFT-WALL### 40 . 1 a 3 increase 2 higher 3 increase 3 increase 4 in 3 increase 6 to 3 increase 17 was 4 in 5 shg 6 to 7 tpf 7 tpf 10 corresponding 9 , 10 corresponding 10 corresponding 11 to 10 corresponding 16 , 11 to 14 treatment 12 a 14 treatment 13 stronger 14 treatment 17 was 18 found 18 found 19 in 18 found 23 whereas 19 in 21 subjects 20 older 21 subjects 22 , 23 whereas 23 whereas 25 effect 24 the 25 effect 25 effect 26 was 26 was 27 found 27 found 28 to 28 to 29 be 29 be 30 negligible 30 negligible 31 in 31 in 39 subjects 32 young 34 and 33 , 34 and 34 and 35 minimal 34 and 39 subjects 35 minimal 36 in 36 in 38 age 37 middle 38 age analysis of collagen images also showed a dependence of the treatment effectiveness with age but with controversial results . 0 ###LEFT-WALL### 1 analysis 0 ###LEFT-WALL### 6 showed 0 ###LEFT-WALL### 19 . 1 analysis 2 of 1 analysis 6 showed 2 of 4 images 3 collagen 4 images 5 also 6 showed 6 showed 8 dependence 6 showed 12 effectiveness 7 a 8 dependence 8 dependence 9 of 9 of 11 treatment 10 the 11 treatment 12 effectiveness 15 but 13 with 14 age 13 with 15 but 15 but 16 with 16 with 18 results 17 controversial 18 results this article describes how the multi - step mid - course assessment of the reach ii community translation project in north carolina was guided by the re - aim framework , and summarizes adaptations made to enhance the feasibility of adoption and maintenance while at the same time assuring fidelity to program core elements . 0 ###LEFT-WALL### 2 article 0 ###LEFT-WALL### 32 and 0 ###LEFT-WALL### 55 . 1 this 2 article 2 article 32 and 3 describes 4 how 3 describes 32 and 4 how 12 assessment 4 how 24 guided 5 the 12 assessment 6 multi 7 - 6 multi 8 step 8 step 12 assessment 9 mid 10 - 9 mid 11 course 11 course 12 assessment 12 assessment 13 of 12 assessment 23 was 13 of 19 project 14 the 19 project 15 reach 16 ii 15 reach 18 translation 17 community 18 translation 18 translation 19 project 19 project 20 in 20 in 22 carolina 21 north 22 carolina 23 was 24 guided 24 guided 25 by 25 by 30 framework 26 the 30 framework 27 re 29 aim 28 - 29 aim 29 aim 30 framework 31 , 32 and 32 and 33 summarizes 33 summarizes 34 adaptations 33 summarizes 36 to 33 summarizes 44 while 34 adaptations 35 made 36 to 37 enhance 37 enhance 39 feasibility 38 the 39 feasibility 39 feasibility 40 of 40 of 42 and 41 adoption 42 and 42 and 43 maintenance 44 while 45 at 45 at 48 time 46 the 47 same 47 same 48 time 48 time 49 assuring 48 time 51 to 49 assuring 50 fidelity 51 to 54 elements 52 program 53 core 53 core 54 elements the two [-] stage assessment involved both quantitative [(] survey [ )(and qualitative ( discussion [group] ) components . 0 ###LEFT-WALL### 12 )(and 0 ###LEFT-WALL### 19 . 1 the 10 survey 2 two 4 stage 4 stage 6 involved 5 assessment 6 involved 6 involved 10 survey 7 both 8 quantitative 8 quantitative 10 survey 10 survey 12 )(and 12 )(and 18 components 13 qualitative 15 discussion 13 qualitative 17 ) 13 qualitative 18 components 14 ( 15 discussion 15 discussion 17 ) results indicated a need to focus primarily on tailoring pre - intervention training , streamlining and clarifying intervention guides and tools , targeting specific participant recruitment messages , addressing issues of session length , and clarifying what flexibilities family consultants could exercise in terms of specific session content addressed and other supportive materials used . 0 ###LEFT-WALL### 20 and 0 ###LEFT-WALL### 22 , 0 ###LEFT-WALL### 55 . 1 results 20 and 2 indicated 4 need 2 indicated 5 to 2 indicated 7 primarily 2 indicated 20 and 3 a 4 need 5 to 6 focus 7 primarily 8 on 8 on 16 and 9 tailoring 12 intervention 10 pre 11 - 10 pre 12 intervention 12 intervention 13 training 13 training 14 , 14 , 15 streamlining 14 , 16 and 16 and 19 guides 17 clarifying 18 intervention 18 intervention 19 guides 20 and 21 tools 22 , 35 and 23 targeting 27 messages 24 specific 25 participant 25 participant 27 messages 26 recruitment 27 messages 27 messages 28 , 28 , 30 issues 28 , 35 and 29 addressing 30 issues 30 issues 31 of 31 of 33 length 32 session 33 length 34 , 35 and 35 and 36 clarifying 35 and 37 what 35 and 42 exercise 37 what 38 flexibilities 37 what 41 could 38 flexibilities 40 consultants 39 family 40 consultants 41 could 42 exercise 42 exercise 43 in 43 in 44 terms 44 terms 45 of 45 of 50 and 46 specific 47 session 47 session 48 content 48 content 49 addressed 48 content 50 and 50 and 53 materials 51 other 53 materials 52 supportive 53 materials 53 materials 54 used the use of the re - aim framework and the mixed [-] method process allowed the program staff to thoroughly assess program satisfaction and areas of concern , and ultimately ensured that the family consultants implementing the intervention had a voice in the adaptation process . 0 ###LEFT-WALL### 2 use 0 ###LEFT-WALL### 29 and 0 ###LEFT-WALL### 46 . 1 the 2 use 2 use 3 of 2 use 29 and 3 of 9 and 4 the 8 framework 5 re 7 aim 6 - 7 aim 7 aim 8 framework 8 framework 9 and 9 and 14 process 10 the 14 process 11 mixed 13 method 13 method 14 process 15 allowed 18 staff 15 allowed 19 to 15 allowed 21 assess 15 allowed 29 and 16 the 18 staff 17 program 18 staff 19 to 21 assess 20 thoroughly 21 assess 21 assess 24 and 22 program 23 satisfaction 23 satisfaction 24 and 24 and 25 areas 25 areas 26 of 26 of 27 concern 28 , 29 and 29 and 31 ensured 30 ultimately 31 ensured 31 ensured 32 that 32 that 35 consultants 32 that 39 had 33 the 35 consultants 34 family 35 consultants 35 consultants 36 implementing 35 consultants 39 had 36 implementing 38 intervention 37 the 38 intervention 39 had 41 voice 39 had 42 in 40 a 41 voice 42 in 45 process 43 the 45 process 44 adaptation 45 process this paper presents a case study exploring an older woman 's perspective on the quality of her life with dementia . 0 ###LEFT-WALL### 2 paper 0 ###LEFT-WALL### 3 presents 0 ###LEFT-WALL### 21 . 1 this 2 paper 2 paper 3 presents 3 presents 6 study 3 presents 19 with 4 a 6 study 5 case 6 study 6 study 7 exploring 7 exploring 12 perspective 7 exploring 13 on 8 an 10 woman 9 older 10 woman 10 woman 11 's 11 's 12 perspective 13 on 15 quality 14 the 15 quality 15 quality 16 of 16 of 18 life 17 her 18 life 19 with 20 dementia the case study establishes the importance of coherence across the life course in understanding how she evaluates her changed situation in the present compared to the past . 0 ###LEFT-WALL### 3 study 0 ###LEFT-WALL### 4 establishes 0 ###LEFT-WALL### 28 . 1 the 3 study 2 case 3 study 3 study 4 establishes 4 establishes 6 importance 4 establishes 9 across 4 establishes 13 in 5 the 6 importance 6 importance 7 of 7 of 8 coherence 9 across 12 course 10 the 12 course 11 life 12 course 13 in 14 understanding 14 understanding 15 how 15 how 16 she 15 how 17 evaluates 16 she 17 evaluates 17 evaluates 20 situation 17 evaluates 21 in 17 evaluates 25 to 18 her 20 situation 19 changed 20 situation 21 in 23 present 22 the 23 present 23 present 24 compared 25 to 27 past 26 the 27 past the metaphoric description of moving from ['] up there ['] to ['] down here ['] represents the perceived struggle to maintain a sense of worth despite a marginalised social position . 0 ###LEFT-WALL### 3 description 0 ###LEFT-WALL### 16 represents 0 ###LEFT-WALL### 31 . 1 the 3 description 2 metaphoric 3 description 3 description 4 of 3 description 11 to 3 description 13 down 3 description 16 represents 4 of 5 moving 5 moving 6 from 6 from 8 up 8 up 9 there 11 to 13 down 13 down 14 here 16 represents 19 struggle 16 represents 20 to 17 the 19 struggle 18 perceived 19 struggle 20 to 21 maintain 21 maintain 23 sense 21 maintain 26 despite 22 a 23 sense 23 sense 24 of 24 of 25 worth 26 despite 30 position 27 a 30 position 28 marginalised 29 social 29 social 30 position being able to define self [and] social identity in ways that preserve a sense of social status is important to find meaning in everyday life . 0 ###LEFT-WALL### 1 being 0 ###LEFT-WALL### 18 is 0 ###LEFT-WALL### 26 . 1 being 2 able 1 being 15 of 1 being 18 is 2 able 3 to 2 able 4 define 3 to 4 define 4 define 8 identity 4 define 9 in 5 self 8 identity 7 social 8 identity 9 in 10 ways 10 ways 11 that 10 ways 12 preserve 11 that 12 preserve 12 preserve 14 sense 13 a 14 sense 15 of 17 status 16 social 17 status 18 is 19 important 19 important 20 to 19 important 21 find 20 to 21 find 21 find 22 meaning 22 meaning 23 in 23 in 25 life 24 everyday 25 life finding meaning involves looking backwards to sustain continuity with the past and looking forwards to maintain momentum and keep going . 0 ###LEFT-WALL### 2 meaning 0 ###LEFT-WALL### 3 involves 0 ###LEFT-WALL### 21 . 1 finding 2 meaning 2 meaning 3 involves 3 involves 4 looking 4 looking 5 backwards 4 looking 6 to 4 looking 9 with 4 looking 15 to 4 looking 20 going 6 to 7 sustain 7 sustain 8 continuity 9 with 12 and 10 the 11 past 11 past 12 and 12 and 14 forwards 13 looking 14 forwards 15 to 18 and 16 maintain 17 momentum 16 maintain 18 and 18 and 19 keep a narrative framework is valuable in showing that quality of life is a dimension of meaning associated with maintaining a sense of social worth . 0 ###LEFT-WALL### 3 framework 0 ###LEFT-WALL### 25 . 1 a 3 framework 2 narrative 3 framework 3 framework 4 is 4 is 5 valuable 5 valuable 6 in 6 in 7 showing 7 showing 8 that 8 that 9 quality 8 that 12 is 9 quality 10 of 9 quality 12 is 10 of 11 life 12 is 14 dimension 13 a 14 dimension 14 dimension 15 of 15 of 16 meaning 16 meaning 17 associated 16 meaning 18 with 16 meaning 22 of 18 with 19 maintaining 19 maintaining 21 sense 20 a 21 sense 22 of 24 worth 23 social 24 worth we employed an auto [-] ethnography approach to explore the affective dimension of life review sessions with community [-] dwelling older military veterans with minor cognitive impairment ( mci ) and early dementia . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 employed 0 ###LEFT-WALL### 34 . 1 we 2 employed 2 employed 7 approach 2 employed 8 to 2 employed 17 with 3 an 7 approach 4 auto 7 approach 6 ethnography 7 approach 8 to 9 explore 9 explore 12 dimension 10 the 12 dimension 11 affective 12 dimension 12 dimension 13 of 13 of 16 sessions 14 life 16 sessions 15 review 16 sessions 17 with 31 and 18 community 20 dwelling 20 dwelling 23 veterans 21 older 23 veterans 22 military 23 veterans 23 veterans 24 with 23 veterans 31 and 24 with 27 impairment 25 minor 27 impairment 26 cognitive 27 impairment 27 impairment 29 mci 28 ( 29 mci 29 mci 30 ) 31 and 33 dementia 32 early 33 dementia using researchers ' analytic memos , we identified facilitators ' interactional strategies that fostered the participant 's sense of personal identity , dignity and social self - worth . 0 ###LEFT-WALL### 7 we 0 ###LEFT-WALL### 8 identified 0 ###LEFT-WALL### 27 - 0 ###LEFT-WALL### 29 . 1 using 5 memos 1 using 6 , 1 using 7 we 2 researchers 3 ' 3 ' 5 memos 4 analytic 5 memos 7 we 8 identified 8 identified 12 strategies 9 facilitators 10 ' 10 ' 12 strategies 11 interactional 12 strategies 12 strategies 13 that 12 strategies 14 fostered 13 that 14 fostered 14 fostered 18 sense 15 the 16 participant 16 participant 17 's 17 's 18 sense 18 sense 19 of 19 of 24 and 20 personal 21 identity 21 identity 22 , 22 , 23 dignity 22 , 24 and 24 and 26 self 25 social 26 self 27 - 28 worth interaction among participant [,] caregiver , and facilitators evoked a range of emotional responses , offering a window into the affective world of mci and early dementia . 0 ###LEFT-WALL### 7 and 0 ###LEFT-WALL### 9 evoked 1 interaction 2 among 1 interaction 7 and 2 among 5 caregiver 3 participant 5 caregiver 6 , 7 and 7 and 8 facilitators 7 and 9 evoked 9 evoked 11 range 10 a 11 range 11 range 12 of 11 range 16 offering 12 of 14 responses 13 emotional 14 responses 15 , 16 offering 16 offering 18 window 16 offering 19 into 16 offering 28 . 17 a 18 window 19 into 25 and 20 the 22 world 21 affective 22 world 22 world 23 of 22 world 25 and 23 of 24 mci 25 and 27 dementia 26 early 27 dementia positive emotional responses outnumbered negative emotional responses by a ratio of two - to - one in the life review sessions ; however , negative emotions were more revelatory of current struggles with declines in health and function . 0 ###LEFT-WALL### 3 responses 0 ###LEFT-WALL### 4 outnumbered 0 ###LEFT-WALL### 22 ; 0 ###LEFT-WALL### 39 . 1 positive 3 responses 2 emotional 3 responses 3 responses 4 outnumbered 4 outnumbered 7 responses 4 outnumbered 8 by 5 negative 7 responses 6 emotional 7 responses 8 by 10 ratio 9 a 10 ratio 10 ratio 11 of 10 ratio 14 to 11 of 12 two 13 - 14 to 14 to 16 one 14 to 22 ; 15 - 16 one 16 one 17 in 17 in 21 sessions 18 the 21 sessions 19 life 20 review 20 review 21 sessions 22 ; 26 emotions 22 ; 37 and 23 however 24 , 23 however 26 emotions 25 negative 26 emotions 26 emotions 37 and 27 were 29 revelatory 27 were 37 and 28 more 29 revelatory 29 revelatory 30 of 29 revelatory 33 with 30 of 32 struggles 31 current 32 struggles 33 with 34 declines 34 declines 35 in 35 in 36 health 37 and 38 function facilitators utilized two interactional strategies , in particular , to foster personhood and social value of participants : focusing on the participant and creating an empathic connection with the participant . 0 ###LEFT-WALL### 1 facilitators 0 ###LEFT-WALL### 2 utilized 0 ###LEFT-WALL### 9 , 0 ###LEFT-WALL### 31 . 1 facilitators 2 utilized 2 utilized 5 strategies 3 two 5 strategies 4 interactional 5 strategies 5 strategies 8 particular 6 , 8 particular 7 in 8 particular 8 particular 9 , 9 , 10 to 9 , 11 foster 9 , 13 and 10 to 11 foster 11 foster 12 personhood 13 and 15 value 13 and 18 : 14 social 15 value 15 value 16 of 15 value 18 : 16 of 17 participants 18 : 19 focusing 19 focusing 20 on 19 focusing 27 connection 19 focusing 28 with 20 on 23 and 21 the 22 participant 22 participant 23 and 23 and 24 creating 25 an 26 empathic 25 an 27 connection 26 empathic 27 connection 28 with 30 participant 29 the 30 participant sleep disturbances are common with dementia and can adversely [affect] waking function . 0 ###LEFT-WALL### 2 disturbances 0 ###LEFT-WALL### 3 are 0 ###LEFT-WALL### 7 and 0 ###LEFT-WALL### 13 . 1 sleep 2 disturbances 2 disturbances 3 are 3 are 4 common 4 common 5 with 5 with 6 dementia 7 and 8 can 7 and 12 function 8 can 11 waking 8 can 12 function 9 adversely 11 waking however , the perspectives of people with dementia and their family caregivers concerning their sleep are [under] - researched . 0 ###LEFT-WALL### 4 perspectives 0 ###LEFT-WALL### 16 are 1 however 2 , 1 however 4 perspectives 3 the 4 perspectives 4 perspectives 5 of 4 perspectives 16 are 5 of 6 people 6 people 7 with 7 with 9 and 8 dementia 9 and 9 and 12 caregivers 9 and 13 concerning 10 their 12 caregivers 11 family 12 caregivers 13 concerning 15 sleep 14 their 15 sleep 16 are 19 researched 18 - 19 researched 19 researched 20 . we conducted three focus groups with 12 community [-] dwelling pairs ( a person with dementia and their family caregiver ) . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 conducted 0 ###LEFT-WALL### 22 . 1 we 2 conducted 2 conducted 5 groups 2 conducted 6 with 3 three 5 groups 4 focus 5 groups 6 with 11 pairs 7 12 11 pairs 8 community 10 dwelling 10 dwelling 11 pairs 11 pairs 17 and 12 ( 17 and 13 a 14 person 14 person 15 with 14 person 17 and 15 with 16 dementia 17 and 20 caregiver 17 and 21 ) 18 their 20 caregiver 19 family 20 caregiver discussions addressed sleep disturbances , coping strategies , and beliefs and attitudes surrounding sleep . 0 ###LEFT-WALL### 1 discussions 0 ###LEFT-WALL### 2 addressed 0 ###LEFT-WALL### 15 . 1 discussions 2 addressed 2 addressed 11 and 3 sleep 4 disturbances 4 disturbances 5 , 5 , 7 strategies 5 , 9 and 6 coping 7 strategies 8 , 9 and 9 and 10 beliefs 9 and 11 and 11 and 12 attitudes 11 and 13 surrounding 13 surrounding 14 sleep thematic analysis indicated that dementia - related sleep disturbances were common , including confused awakenings and dementia - related behaviors at night , changes to sleep timing , and nightmares . 0 ###LEFT-WALL### 1 thematic 0 ###LEFT-WALL### 10 were 0 ###LEFT-WALL### 19 related 0 ###LEFT-WALL### 31 . 1 thematic 10 were 2 analysis 3 indicated 3 indicated 9 disturbances 4 that 5 dementia 5 dementia 6 - 5 dementia 9 disturbances 7 related 9 disturbances 8 sleep 9 disturbances 9 disturbances 10 were 10 were 11 common 11 common 13 including 12 , 13 including 13 including 16 and 13 including 18 - 14 confused 15 awakenings 15 awakenings 16 and 16 and 17 dementia 16 and 18 - 18 - 19 related 19 related 20 behaviors 19 related 21 at 21 at 29 and 22 night 24 changes 22 night 29 and 23 , 24 changes 24 changes 25 to 24 changes 28 , 25 to 27 timing 26 sleep 27 timing 28 , 29 and 29 and 30 nightmares common issues for caregivers included being woken at night , having problems getting back to sleep , trips to the bathroom , and daytime sleepiness . 0 ###LEFT-WALL### 23 and 0 ###LEFT-WALL### 26 . 1 common 2 issues 2 issues 3 for 2 issues 23 and 3 for 4 caregivers 4 caregivers 5 included 4 caregivers 6 being 4 caregivers 11 having 6 being 7 woken 7 woken 8 at 8 at 9 night 10 , 11 having 11 having 12 problems 11 having 22 , 12 problems 13 getting 12 problems 18 trips 13 getting 14 back 13 getting 15 to 15 to 16 sleep 17 , 18 trips 18 trips 19 to 18 trips 22 , 19 to 21 bathroom 20 the 21 bathroom 23 and 25 sleepiness 24 daytime 25 sleepiness participants often normalized their sleeping problems and had developed a number of coping strategies . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 7 and 0 ###LEFT-WALL### 15 . 1 participants 7 and 2 often 3 normalized 3 normalized 6 problems 3 normalized 7 and 4 their 6 problems 5 sleeping 6 problems 7 and 8 had 8 had 9 developed 9 developed 14 strategies 10 a 11 number 11 number 12 of 11 number 14 strategies 12 of 14 strategies 13 coping 14 strategies these findings highlight the impact [that] sleep disturbances can have on people living with dementia . 0 ###LEFT-WALL### 2 findings 0 ###LEFT-WALL### 3 highlight 0 ###LEFT-WALL### 16 . 1 these 2 findings 2 findings 3 highlight 3 highlight 5 impact 4 the 5 impact 5 impact 8 disturbances 5 impact 10 have 7 sleep 8 disturbances 8 disturbances 9 can 9 can 10 have 10 have 11 on 11 on 12 people 12 people 13 living 13 living 14 with 14 with 15 dementia their experiences and beliefs need to be considered for developing effective interventions to improve sleep , waking function , and wellbeing . 0 ###LEFT-WALL### 2 experiences 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 22 . 1 their 2 experiences 3 and 4 beliefs 3 and 5 need 4 beliefs 5 need 5 need 6 to 5 need 8 considered 6 to 7 be 7 be 8 considered 8 considered 9 for 8 considered 13 to 9 for 10 developing 10 developing 12 interventions 11 effective 12 interventions 13 to 14 improve 14 improve 20 and 15 sleep 16 , 16 , 18 function 16 , 20 and 17 waking 18 function 19 , 20 and 20 and 21 wellbeing down 's syndrome ( ds ) , the most common chromosomal disorder , is caused by 21 trisomy and is featured by intellectual disability . 0 ###LEFT-WALL### 3 syndrome 0 ###LEFT-WALL### 19 and 0 ###LEFT-WALL### 25 . 1 down 2 's 2 's 3 syndrome 3 syndrome 5 ds 3 syndrome 12 disorder 3 syndrome 19 and 4 ( 5 ds 5 ds 6 ) 7 , 12 disorder 8 the 9 most 9 most 12 disorder 10 common 12 disorder 11 chromosomal 12 disorder 12 disorder 13 , 14 is 15 caused 14 is 19 and 15 caused 16 by 16 by 18 trisomy 17 21 18 trisomy 19 and 20 is 20 is 21 featured 21 featured 22 by 22 by 24 disability 23 intellectual 24 disability subjects with ds can develop some traits of alzheimer disease ( ad ) at an earlier age than subjects [without] trisomy 21 . 0 ###LEFT-WALL### 1 subjects 0 ###LEFT-WALL### 5 develop 0 ###LEFT-WALL### 18 than 0 ###LEFT-WALL### 23 . 1 subjects 2 with 1 subjects 4 can 2 with 3 ds 4 can 5 develop 5 develop 7 traits 5 develop 14 at 6 some 7 traits 7 traits 8 of 8 of 10 disease 9 alzheimer 10 disease 10 disease 12 ad 11 ( 12 ad 12 ad 13 ) 14 at 17 age 15 an 17 age 16 earlier 17 age 18 than 19 subjects 18 than 21 trisomy 19 subjects 21 trisomy 21 trisomy 22 21 apoptosis is a programmed cell death process under both normal physiological and pathological conditions . 0 ###LEFT-WALL### 1 apoptosis 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 15 . 1 apoptosis 2 is 2 is 7 process 2 is 8 under 3 a 7 process 4 programmed 5 cell 5 cell 7 process 6 death 7 process 8 under 14 conditions 9 both 14 conditions 10 normal 14 conditions 11 physiological 12 and 12 and 13 pathological 12 and 14 conditions caspase - 3 ( casp3 ) plays an important role in neuronal death during nervous system development and under certain pathological conditions . 0 ###LEFT-WALL### 1 caspase 0 ###LEFT-WALL### 7 plays 0 ###LEFT-WALL### 23 . 1 caspase 3 3 1 caspase 7 plays 2 - 3 3 3 3 5 casp3 3 3 6 ) 4 ( 5 casp3 5 casp3 6 ) 7 plays 10 role 7 plays 11 in 8 an 9 important 8 an 10 role 9 important 10 role 11 in 13 death 12 neuronal 13 death 13 death 18 and 14 during 17 development 14 during 18 and 15 nervous 16 system 16 system 17 development 18 and 19 under 19 under 22 conditions 20 certain 22 conditions 21 pathological 22 conditions furthermore , in vitro [and] in vivo studies report elevated expression and activation of casp3 in models of ad . 0 ###LEFT-WALL### 8 studies 0 ###LEFT-WALL### 9 report 0 ###LEFT-WALL### 20 . 1 furthermore 2 , 1 furthermore 8 studies 3 in 4 vitro 4 vitro 8 studies 6 in 7 vivo 7 vivo 8 studies 8 studies 9 report 9 report 12 and 9 report 16 in 10 elevated 11 expression 11 expression 12 and 12 and 13 activation 12 and 14 of 14 of 15 casp3 16 in 17 models 17 models 18 of 18 of 19 ad on this account , the expression of casp3 [gene] was evaluated in cultures of fibroblasts of ds and normal subjects by flow cytometry . 0 ###LEFT-WALL### 6 expression 0 ###LEFT-WALL### 11 evaluated 0 ###LEFT-WALL### 18 and 0 ###LEFT-WALL### 24 . 1 on 3 account 1 on 4 , 1 on 6 expression 2 this 3 account 5 the 6 expression 6 expression 7 of 6 expression 10 was 7 of 8 casp3 10 was 11 evaluated 11 evaluated 12 in 12 in 13 cultures 13 cultures 14 of 14 of 15 fibroblasts 15 fibroblasts 16 of 16 of 17 ds 18 and 20 subjects 18 and 23 cytometry 19 normal 20 subjects 20 subjects 21 by 20 subjects 23 cytometry 21 by 22 flow casp3 protein was up - regulated in fibroblasts of ds . 0 ###LEFT-WALL### 2 protein 0 ###LEFT-WALL### 3 was 1 casp3 2 protein 2 protein 3 was 3 was 4 up 4 up 6 regulated 5 - 6 regulated 6 regulated 7 in 6 regulated 11 . 7 in 8 fibroblasts 8 fibroblasts 9 of 9 of 10 ds the data obtained from this study strengthen the hypothesis that the [over] [-] expression of casp3 [gene] could have a role in the activation of the apoptotic pathways acting in the neurodegenerative processes in ds . 0 ###LEFT-WALL### 2 data 0 ###LEFT-WALL### 7 strengthen 0 ###LEFT-WALL### 36 . 1 the 2 data 2 data 3 obtained 2 data 7 strengthen 3 obtained 4 from 4 from 6 study 5 this 6 study 7 strengthen 9 hypothesis 7 strengthen 30 in 7 strengthen 34 in 8 the 9 hypothesis 9 hypothesis 10 that 10 that 14 expression 10 that 19 have 11 the 14 expression 14 expression 15 of 14 expression 18 could 15 of 16 casp3 18 could 19 have 19 have 21 role 19 have 22 in 20 a 21 role 22 in 24 activation 23 the 24 activation 24 activation 25 of 24 activation 29 acting 25 of 28 pathways 26 the 28 pathways 27 apoptotic 28 pathways 30 in 33 processes 31 the 33 processes 32 neurodegenerative 33 processes 34 in 35 ds background : the relationship between osteoporosis ( op [ )(and osteoarthritis ( oa ) is yet unclear . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 4 relationship 2 : 15 is 2 : 18 . 3 the 4 relationship 4 relationship 5 between 4 relationship 15 is 5 between 6 osteoporosis 6 osteoporosis 10 )(and 7 ( 10 )(and 8 op 10 )(and 10 )(and 11 osteoarthritis 10 )(and 13 oa 10 )(and 14 ) 12 ( 13 oa 13 oa 14 ) 15 is 16 yet 15 is 17 unclear aim : to evaluate the possible effect of op on the femoral cartilage thickness in female patients with knee oa . 0 ###LEFT-WALL### 1 aim 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 21 . 2 : 3 to 2 : 4 evaluate 3 to 4 evaluate 4 evaluate 7 effect 4 evaluate 10 on 4 evaluate 15 in 5 the 7 effect 6 possible 7 effect 7 effect 8 of 8 of 9 op 10 on 14 thickness 11 the 14 thickness 12 femoral 13 cartilage 13 cartilage 14 thickness 15 in 17 patients 16 female 17 patients 17 patients 18 with 18 with 20 oa 19 knee 20 oa materials and methods : eighty patients with a diagnosis of knee oa were enrolled . 0 ###LEFT-WALL### 3 methods 0 ###LEFT-WALL### 4 : 1 materials 2 and 2 and 3 methods 4 : 6 patients 4 : 14 enrolled 4 : 15 . 5 eighty 6 patients 6 patients 7 with 6 patients 10 of 6 patients 13 were 7 with 9 diagnosis 8 a 9 diagnosis 10 of 12 oa 11 knee 12 oa 13 were 14 enrolled forty subjects who also had op comprised group i and the remaining 40 oa subjects comprised group ii . 0 ###LEFT-WALL### 2 subjects 0 ###LEFT-WALL### 16 comprised 0 ###LEFT-WALL### 19 . 1 forty 2 subjects 2 subjects 3 who 2 subjects 5 had 2 subjects 7 comprised 3 who 5 had 4 also 5 had 5 had 6 op 7 comprised 8 group 8 group 10 and 8 group 16 comprised 9 i 10 and 10 and 15 subjects 10 and 16 comprised 11 the 12 remaining 11 the 13 40 13 40 15 subjects 14 oa 15 subjects 16 comprised 17 group 17 group 18 ii antero - posterior knee [radiographs] [were] obtained [in] standing position and they were evaluated according to kelgren - lawrence ( k - l ) grading scale . 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 14 evaluated 0 ###LEFT-WALL### 18 - 1 antero 2 - 1 antero 11 and 3 posterior 4 knee 4 knee 10 position 7 obtained 9 standing 9 standing 10 position 10 position 11 and 11 and 12 they 11 and 13 were 13 were 14 evaluated 14 evaluated 16 to 15 according 16 to 16 to 17 kelgren 18 - 26 scale 18 - 27 . 19 lawrence 26 scale 20 ( 22 - 21 k 22 - 22 - 23 l 22 - 24 ) 22 - 26 scale 25 grading 26 scale femoral cartilage evaluations were performed using a linear array us probe ( 7 - 12 mhz ) . 0 ###LEFT-WALL### 3 evaluations 0 ###LEFT-WALL### 5 performed 0 ###LEFT-WALL### 18 . 1 femoral 2 cartilage 2 cartilage 3 evaluations 3 evaluations 4 were 4 were 5 performed 5 performed 6 using 5 performed 14 - 6 using 11 probe 7 a 8 linear 7 a 11 probe 8 linear 9 array 9 array 11 probe 10 us 11 probe 12 ( 14 - 13 7 14 - 14 - 16 mhz 14 - 17 ) 15 12 16 mhz in addition , ultrasonographic femoral cartilage grading was also performed for each knee . 0 ###LEFT-WALL### 7 grading 0 ###LEFT-WALL### 10 performed 0 ###LEFT-WALL### 14 . 1 in 2 addition 1 in 3 , 1 in 7 grading 4 ultrasonographic 6 cartilage 5 femoral 6 cartilage 6 cartilage 7 grading 7 grading 8 was 8 was 9 also 8 was 10 performed 10 performed 11 for 11 for 13 knee 12 each 13 knee results : left knee scores pertaining to both gradings were found to be lower ( p = 0.02 , p = 0.04 , respectively ) in group i when compared with those of group ii . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 13 be 0 ###LEFT-WALL### 36 . 2 : 13 be 3 left 11 found 4 knee 5 scores 5 scores 6 pertaining 5 scores 7 to 5 scores 10 were 7 to 9 gradings 8 both 9 gradings 10 were 11 found 11 found 12 to 12 to 13 be 13 be 14 lower 14 lower 17 = 14 lower 21 = 14 lower 24 respectively 14 lower 26 in 14 lower 29 when 14 lower 31 with 15 ( 17 = 16 p 17 = 17 = 18 0.02 17 = 19 , 20 p 21 = 21 = 22 0.04 23 , 24 respectively 24 respectively 25 ) 26 in 27 group 27 group 28 i 29 when 30 compared 31 with 32 those 32 those 33 of 33 of 34 group 34 group 35 ii the two grading scores were positively correlated for both knees - statistically significant only for the right side ( r = 0.727 , p = 0.01 ) . 0 ###LEFT-WALL### 2 two 0 ###LEFT-WALL### 7 correlated 0 ###LEFT-WALL### 28 . 1 the 2 two 2 two 3 grading 2 two 5 were 3 grading 4 scores 5 were 7 correlated 6 positively 7 correlated 7 correlated 8 for 7 correlated 11 - 7 correlated 13 significant 8 for 10 knees 9 both 10 knees 12 statistically 13 significant 13 significant 14 only 13 significant 15 for 13 significant 21 = 13 significant 25 = 15 for 18 side 16 the 18 side 17 right 18 side 19 ( 21 = 20 r 21 = 21 = 22 0.727 21 = 23 , 23 , 25 = 24 p 25 = 25 = 26 0.01 25 = 27 ) no significant difference was found between the groups in terms of femoral cartilage thicknesses ( [all] p > 0.05 ) . 0 ###LEFT-WALL### 3 difference 0 ###LEFT-WALL### 5 found 0 ###LEFT-WALL### 21 . 1 no 3 difference 2 significant 3 difference 3 difference 4 was 4 was 5 found 5 found 6 between 5 found 9 in 6 between 8 groups 7 the 8 groups 9 in 10 terms 10 terms 11 of 11 of 14 thicknesses 12 femoral 13 cartilage 13 cartilage 14 thicknesses 14 thicknesses 18 > 15 ( 18 > 17 p 18 > 18 > 19 0.05 18 > 20 ) discussion : ultrasonographic and roentgenographic gradings were consistent and patients with op had lower scores for both gradings . 0 ###LEFT-WALL### 1 discussion 0 ###LEFT-WALL### 2 : 2 : 4 and 2 : 7 were 2 : 9 and 2 : 19 . 3 ultrasonographic 4 and 4 and 6 gradings 4 and 7 were 5 roentgenographic 6 gradings 7 were 8 consistent 9 and 10 patients 9 and 13 had 10 patients 11 with 10 patients 13 had 11 with 12 op 13 had 15 scores 14 lower 15 scores 15 scores 16 for 16 for 18 gradings 17 both 18 gradings on the other hand , the presence of op did not seem to have any effect on cartilage thickness measurements . 0 ###LEFT-WALL### 7 presence 0 ###LEFT-WALL### 12 seem 0 ###LEFT-WALL### 21 . 1 on 4 hand 1 on 5 , 1 on 7 presence 2 the 3 other 3 other 4 hand 6 the 7 presence 7 presence 8 of 7 presence 10 did 8 of 9 op 10 did 11 not 10 did 12 seem 12 seem 13 to 12 seem 14 have 13 to 14 have 14 have 16 effect 14 have 17 on 15 any 16 effect 17 on 20 measurements 18 cartilage 20 measurements 19 thickness 20 measurements conclusions : to the best knowledge of the authors , this study is the first to have explored the impact of op on oa using us in the literature . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 10 , 0 ###LEFT-WALL### 30 . 1 conclusions 2 : 2 : 3 to 3 to 6 knowledge 4 the 5 best 4 the 6 knowledge 6 knowledge 7 of 7 of 9 authors 8 the 9 authors 10 , 12 study 10 , 13 is 11 this 12 study 12 study 13 is 13 is 15 first 14 the 15 first 15 first 16 to 15 first 18 explored 16 to 17 have 17 have 18 explored 18 explored 20 impact 19 the 20 impact 20 impact 21 of 21 of 22 op 22 op 23 on 23 on 24 oa 24 oa 25 using 25 using 26 us 26 us 27 in 27 in 29 literature 28 the 29 literature purpose : the clinical effects of osteoporosis include pain , fractures , and physical disability , causing a loss of independence and necessitating long - term care . 0 ###LEFT-WALL### 1 purpose 0 ###LEFT-WALL### 2 : 2 : 13 and 2 : 28 . 3 the 5 effects 4 clinical 5 effects 5 effects 6 of 5 effects 10 , 6 of 9 pain 7 osteoporosis 8 include 8 include 9 pain 10 , 11 fractures 10 , 13 and 12 , 13 and 13 and 15 disability 13 and 16 , 13 and 17 causing 13 and 20 of 14 physical 15 disability 17 causing 19 loss 18 a 19 loss 20 of 22 and 21 independence 22 and 22 and 27 care 23 necessitating 27 care 24 long 25 - 24 long 26 term 26 term 27 care whereas the effects of exercise therapy in decreasing body mass index [and] preventing fractures are well established , there is no consensus on back pain and quality of life in women with osteoporosis . 0 ###LEFT-WALL### 19 there 0 ###LEFT-WALL### 20 is 0 ###LEFT-WALL### 34 . 1 whereas 3 effects 1 whereas 17 established 1 whereas 18 , 1 whereas 19 there 2 the 3 effects 3 effects 4 of 3 effects 7 in 3 effects 15 are 4 of 6 therapy 5 exercise 6 therapy 7 in 8 decreasing 8 decreasing 14 fractures 9 body 14 fractures 10 mass 14 fractures 11 index 14 fractures 13 preventing 14 fractures 15 are 17 established 16 well 17 established 19 there 20 is 20 is 22 consensus 21 no 22 consensus 22 consensus 23 on 23 on 26 and 24 back 25 pain 25 pain 26 and 26 and 27 quality 26 and 28 of 26 and 30 in 28 of 29 life 30 in 31 women 31 women 32 with 32 with 33 osteoporosis the aim of this study was to determine the efficacy of a brief course of rehabilitation , comprising group - adapted physical exercises , with regard to back pain , disability , and quality of life in women with postmenopausal osteoporosis who had no evidence of fractures . 0 ###LEFT-WALL### 2 aim 0 ###LEFT-WALL### 17 , 0 ###LEFT-WALL### 48 . 1 the 2 aim 2 aim 3 of 2 aim 6 was 3 of 5 study 4 this 5 study 6 was 7 to 6 was 8 determine 7 to 8 determine 8 determine 10 efficacy 9 the 10 efficacy 10 efficacy 11 of 10 efficacy 15 of 11 of 14 course 12 a 13 brief 12 a 14 course 13 brief 14 course 15 of 16 rehabilitation 17 , 19 group 17 , 20 - 18 comprising 19 group 20 - 23 exercises 20 - 30 , 21 adapted 23 exercises 22 physical 23 exercises 23 exercises 25 with 24 , 25 with 25 with 26 regard 25 with 30 , 26 regard 27 to 27 to 29 pain 28 back 29 pain 30 , 33 and 31 disability 33 and 32 , 33 and 33 and 34 quality 33 and 35 of 35 of 36 life 36 life 37 in 36 life 39 with 36 life 46 of 37 in 38 women 39 with 41 osteoporosis 40 postmenopausal 41 osteoporosis 41 osteoporosis 42 who 41 osteoporosis 43 had 42 who 43 had 43 had 45 evidence 44 no 45 evidence 46 of 47 fractures methods : the enrolled patients were randomized into two groups : the treatment group underwent ten sessions of rehabilitative exercises , and the control group received an instructional booklet with descriptions and figures of exercises that were to be performed at home . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 43 . 2 : 5 patients 2 : 7 randomized 2 : 11 : 3 the 5 patients 4 enrolled 5 patients 5 patients 6 were 6 were 7 randomized 7 randomized 8 into 8 into 10 groups 9 two 10 groups 11 : 14 group 11 : 15 underwent 11 : 22 and 11 : 32 and 12 the 14 group 13 treatment 14 group 14 group 15 underwent 15 underwent 17 sessions 16 ten 17 sessions 17 sessions 18 of 18 of 20 exercises 19 rehabilitative 20 exercises 21 , 22 and 22 and 25 group 22 and 26 received 23 the 25 group 24 control 25 group 25 group 26 received 26 received 29 booklet 27 an 28 instructional 27 an 29 booklet 28 instructional 29 booklet 29 booklet 30 with 30 with 31 descriptions 32 and 33 figures 32 and 40 performed 33 figures 34 of 33 figures 36 that 33 figures 37 were 33 figures 40 performed 34 of 35 exercises 36 that 37 were 37 were 38 to 37 were 39 be 38 to 39 be 40 performed 41 at 41 at 42 home results : sixty patients completed the trial and assessments , including a 6 [-] month follow - up . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 1 results 2 : 2 : 4 patients 3 sixty 4 patients 4 patients 5 completed 4 patients 8 and 4 patients 16 follow 6 the 7 trial 7 trial 8 and 8 and 9 assessments 8 and 10 , 8 and 11 including 8 and 16 follow 11 including 15 month 12 a 15 month 13 6 15 month 16 follow 18 up 17 - 18 up 18 up 19 . conclusions : our results suggest that group rehabilitation reduces back pain and improves functional status and quality of life in women with postmenopausal osteoporosis , maintaining these outcomes for 6 months . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 12 and 2 : 4 results 2 : 5 suggest 3 our 4 results 4 results 5 suggest 5 suggest 6 that 6 that 8 rehabilitation 6 that 12 and 7 group 8 rehabilitation 9 reduces 11 pain 9 reduces 12 and 10 back 11 pain 12 and 13 improves 12 and 20 in 12 and 26 maintaining 13 improves 16 and 14 functional 15 status 15 status 16 and 16 and 17 quality 16 and 18 of 18 of 19 life 20 in 21 women 21 women 22 with 22 with 24 osteoporosis 23 postmenopausal 24 osteoporosis 25 , 26 maintaining 26 maintaining 28 outcomes 26 maintaining 32 . 27 these 28 outcomes 28 outcomes 29 for 29 for 31 months 30 6 31 months the use of physical exercises might strengthen the habit to training . 0 ###LEFT-WALL### 2 use 0 ###LEFT-WALL### 7 strengthen 0 ###LEFT-WALL### 12 . 1 the 2 use 2 use 3 of 2 use 6 might 3 of 5 exercises 4 physical 5 exercises 6 might 7 strengthen 7 strengthen 9 habit 7 strengthen 10 to 8 the 9 habit 10 to 11 training background and aims : blood pressure control is closely related to target organ damage in elderly patients with [hypertension] . 0 ###LEFT-WALL### 3 aims 0 ###LEFT-WALL### 4 : 0 ###LEFT-WALL### 20 . 1 background 2 and 2 and 3 aims 3 aims 4 : 4 : 5 blood 5 blood 7 control 5 blood 18 with 6 pressure 7 control 7 control 8 is 8 is 10 related 9 closely 10 related 10 related 11 to 11 to 12 target 12 target 14 damage 12 target 15 in 12 target 18 with 13 organ 14 damage 15 in 17 patients 16 elderly 17 patients the aim of this study was to determine the relationship between ambulatory blood pressure monitoring ( abpm [ )(indices and cardiac damage in elderly male patients with treated essential hypertension [(] eh ) . 0 ###LEFT-WALL### 2 aim 0 ###LEFT-WALL### 34 . 1 the 2 aim 2 aim 3 of 2 aim 6 was 3 of 5 study 4 this 5 study 6 was 7 to 6 was 8 determine 7 to 8 determine 8 determine 10 relationship 8 determine 11 between 9 the 10 relationship 11 between 15 monitoring 12 ambulatory 13 blood 13 blood 15 monitoring 14 pressure 15 monitoring 15 monitoring 20 and 16 ( 20 and 17 abpm 19 )(indices 19 )(indices 20 and 20 and 22 damage 20 and 23 in 20 and 27 with 20 and 33 ) 21 cardiac 22 damage 23 in 26 patients 24 elderly 25 male 25 male 26 patients 27 with 32 eh 28 treated 32 eh 29 essential 30 hypertension 30 hypertension 32 eh method : this study included 998 chinese men ( mean age , 78.44 ± 12.02 years ) with eh . 0 ###LEFT-WALL### 1 method 0 ###LEFT-WALL### 2 : 2 : 4 study 2 : 5 included 2 : 20 . 3 this 4 study 4 study 5 included 5 included 8 men 5 included 18 with 6 998 8 men 7 chinese 8 men 8 men 11 age 8 men 16 years 9 ( 11 age 10 mean 11 age 11 age 12 , 12 , 16 years 13 78.44 16 years 14 ± 16 years 15 12.02 16 years 16 years 17 ) 18 with 19 eh participants underwent cardiac function assessment , laboratory testing , and abpm , including abp , bp variability , bp circadian rhythms , and hypertensive or hypotensive time indices . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 2 underwent 0 ###LEFT-WALL### 29 . 1 participants 2 underwent 2 underwent 23 and 3 cardiac 5 assessment 4 function 5 assessment 5 assessment 6 , 6 , 8 testing 6 , 10 and 7 laboratory 8 testing 9 , 10 and 10 and 11 abpm 10 and 22 , 10 and 23 and 11 abpm 13 including 12 , 13 including 13 including 14 abp 13 including 22 , 14 abp 17 variability 15 , 17 variability 16 bp 17 variability 17 variability 21 rhythms 17 variability 22 , 18 , 21 rhythms 19 bp 21 rhythms 20 circadian 21 rhythms 21 rhythms 22 , 22 , 23 and 23 and 28 indices 24 hypertensive 25 or 25 or 26 hypotensive 25 or 28 indices 27 time 28 indices the relationships between abpm indices and cardiac damage ( expressed by shape and function ) were assessed using ridge regression analysis . 0 ###LEFT-WALL### 2 relationships 0 ###LEFT-WALL### 17 assessed 0 ###LEFT-WALL### 22 . 1 the 2 relationships 2 relationships 3 between 2 relationships 10 expressed 2 relationships 16 were 3 between 6 and 4 abpm 5 indices 5 indices 6 and 6 and 8 damage 7 cardiac 8 damage 9 ( 10 expressed 10 expressed 11 by 10 expressed 15 ) 11 by 13 and 12 shape 13 and 13 and 14 function 16 were 17 assessed 17 assessed 18 using 18 using 21 analysis 19 ridge 21 analysis 20 regression 21 analysis left [ventricular] [mass] ( lvm ) was positively correlated with the 24 hmsbp , dsbp , nsbp [,] 24 [h] mean pulse pressure ( 24 hmpp ) , [day] mean pulse pressure , and nocturnal mean arterial pressure , whereas lvm was negatively correlated with the ndbpf . 0 ###LEFT-WALL### 1 left 0 ###LEFT-WALL### 9 correlated 1 left 5 lvm 1 left 7 was 4 ( 5 lvm 5 lvm 6 ) 7 was 9 correlated 8 positively 9 correlated 9 correlated 10 with 10 with 12 24 10 with 17 nsbp 11 the 12 24 13 hmsbp 14 , 13 hmsbp 17 nsbp 15 dsbp 16 , 15 dsbp 17 nsbp 17 nsbp 19 24 17 nsbp 28 , 19 24 28 , 21 mean 23 pressure 21 mean 28 , 22 pulse 23 pressure 23 pressure 26 hmpp 24 ( 26 hmpp 25 24 26 hmpp 26 hmpp 27 ) 28 , 30 mean 30 mean 34 and 30 mean 40 whereas 31 pulse 32 pressure 32 pressure 34 and 33 , 34 and 34 and 38 pressure 35 nocturnal 38 pressure 36 mean 38 pressure 37 arterial 38 pressure 39 , 40 whereas 40 whereas 41 lvm 40 whereas 44 correlated 40 whereas 48 . 41 lvm 42 was 42 was 44 correlated 43 negatively 44 correlated 44 correlated 45 with 45 with 47 ndbpf 46 the 47 ndbpf conclusions : our study showed that the abpm indices associated with cardiac damage may be regarded as an early predictive marker for cardiac function impairment in elderly male patients with eh . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 32 . 2 : 4 study 2 : 5 showed 3 our 4 study 4 study 5 showed 5 showed 6 that 6 that 8 abpm 6 that 16 regarded 7 the 8 abpm 8 abpm 9 indices 8 abpm 10 associated 8 abpm 14 may 9 indices 10 associated 10 associated 11 with 11 with 13 damage 12 cardiac 13 damage 14 may 15 be 15 be 16 regarded 16 regarded 17 as 16 regarded 22 for 16 regarded 26 in 16 regarded 30 with 17 as 21 marker 18 an 21 marker 19 early 21 marker 20 predictive 21 marker 22 for 25 impairment 23 cardiac 24 function 24 function 25 impairment 26 in 29 patients 27 elderly 28 male 28 male 29 patients 30 with 31 eh background : heart failure ( hf ) is associated with impaired maximal aerobic capacity as indicated by decreases in peak oxygen uptake ( peak vo ( 2 ) ) . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 3 heart 2 : 11 impaired 2 : 30 . 3 heart 4 failure 3 heart 10 with 3 heart 11 impaired 4 failure 6 hf 4 failure 8 is 5 ( 6 hf 6 hf 7 ) 8 is 9 associated 9 associated 10 with 11 impaired 14 capacity 11 impaired 17 by 12 maximal 14 capacity 13 aerobic 14 capacity 14 capacity 16 indicated 15 as 16 indicated 17 by 18 decreases 18 decreases 19 in 19 in 22 uptake 20 peak 22 uptake 21 oxygen 22 uptake 22 uptake 25 vo 23 ( 25 vo 24 peak 25 vo 25 vo 27 2 25 vo 29 ) 26 ( 27 2 27 2 28 ) considering that aging by itself has a negative effect on this variable , the evaluation of maximum capacity is often questioned because current predicted peak vo ( 2 ) is based on subjects without heart disease or [b] - blocker therapy . 0 ###LEFT-WALL### 15 evaluation 0 ###LEFT-WALL### 21 questioned 0 ###LEFT-WALL### 37 or 0 ###LEFT-WALL### 42 . 1 considering 2 that 1 considering 13 , 1 considering 15 evaluation 2 that 3 aging 2 that 6 has 3 aging 4 by 3 aging 6 has 4 by 5 itself 6 has 9 effect 6 has 10 on 7 a 9 effect 8 negative 9 effect 10 on 12 variable 11 this 12 variable 14 the 15 evaluation 15 evaluation 16 of 15 evaluation 19 is 16 of 18 capacity 17 maximum 18 capacity 19 is 20 often 19 is 21 questioned 21 questioned 22 because 21 questioned 32 on 21 questioned 34 without 22 because 26 vo 22 because 31 based 23 current 24 predicted 24 predicted 26 vo 25 peak 26 vo 26 vo 28 2 26 vo 30 is 27 ( 28 2 28 2 29 ) 30 is 31 based 32 on 33 subjects 34 without 36 disease 35 heart 36 disease 37 or 39 - 37 or 40 blocker 39 - 40 blocker 40 blocker 41 therapy in contrast , if decline [in] predicted and attained peak vo ( 2 ) were age - related , proportionally , loss of aerobic function [(] predicted peak vo ( 2 ) , % [ )( [remain] stable over time in these patients . 1 in 2 contrast 1 in 3 , 1 in 11 vo 4 if 5 decline 4 if 8 and 4 if 11 vo 5 decline 8 and 7 predicted 8 and 8 and 9 attained 8 and 10 peak 11 vo 13 2 11 vo 15 were 12 ( 13 2 13 2 14 ) 15 were 16 age 16 age 18 related 16 age 20 proportionally 16 age 22 loss 17 - 18 related 18 related 19 , 19 , 20 proportionally 20 proportionally 21 , 22 loss 23 of 23 of 29 vo 24 aerobic 25 function 25 function 27 predicted 27 predicted 29 vo 28 peak 29 vo 29 vo 31 2 29 vo 38 stable 30 ( 31 2 31 2 32 ) 33 , 38 stable 34 % 38 stable 38 stable 39 over 38 stable 44 . 39 over 40 time 40 time 41 in 41 in 43 patients 42 these 43 patients the purpose of this investigation is to assess the effects of age on peak vo ( 2 ) in hf patients taking [b] - blockers . 0 ###LEFT-WALL### 2 purpose 0 ###LEFT-WALL### 24 - 0 ###LEFT-WALL### 26 . 1 the 2 purpose 2 purpose 3 of 2 purpose 6 is 3 of 5 investigation 4 this 5 investigation 6 is 7 to 6 is 8 assess 7 to 8 assess 8 assess 10 effects 8 assess 13 on 8 assess 19 in 9 the 10 effects 10 effects 11 of 11 of 12 age 13 on 15 vo 14 peak 15 vo 15 vo 17 2 16 ( 17 2 17 2 18 ) 19 in 22 taking 20 hf 22 taking 21 patients 22 taking 24 - 25 blockers linear regression was used to develop the equation to predict peak vo ( 2 ) , based on age . 0 ###LEFT-WALL### 2 regression 0 ###LEFT-WALL### 4 used 0 ###LEFT-WALL### 20 . 1 linear 2 regression 2 regression 3 was 3 was 4 used 4 used 5 to 4 used 16 , 5 to 6 develop 6 develop 8 equation 6 develop 9 to 7 the 8 equation 9 to 16 , 10 predict 12 vo 10 predict 16 , 11 peak 12 vo 12 vo 14 2 13 ( 14 2 14 2 15 ) 16 , 17 based 16 , 18 on 18 on 19 age results : peak vo ( 2 ) decreased 0.9 ml/min/kg per age - [decade] , maximum hr also decreased with aging and ve/vco ( 2 ) slope was similar among all decades . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 15 , 0 ###LEFT-WALL### 33 . 1 results 2 : 2 : 3 peak 3 peak 8 decreased 4 vo 6 2 4 vo 8 decreased 5 ( 6 2 6 2 7 ) 8 decreased 10 ml/min/kg 8 decreased 13 - 9 0.9 10 ml/min/kg 10 ml/min/kg 11 per 11 per 12 age 15 , 17 hr 15 , 18 also 16 maximum 17 hr 18 also 27 slope 18 also 28 was 19 decreased 20 with 19 decreased 26 ) 19 decreased 27 slope 20 with 22 and 21 aging 22 and 22 and 23 ve/vco 22 and 25 2 24 ( 25 2 25 2 26 ) 27 slope 28 was 28 was 29 similar 29 similar 30 among 30 among 32 decades 31 all 32 decades the predicted new [b] - blocker equation to peak vo ( 2 bb ) was 20.934 - 0.092 × age . 0 ###LEFT-WALL### 7 equation 0 ###LEFT-WALL### 15 was 0 ###LEFT-WALL### 21 . 1 the 7 equation 2 predicted 7 equation 3 new 5 - 3 new 7 equation 6 blocker 7 equation 7 equation 8 to 7 equation 13 bb 7 equation 15 was 8 to 10 vo 9 peak 10 vo 11 ( 13 bb 12 2 13 bb 13 bb 14 ) 15 was 20 age 16 20.934 17 - 17 - 18 0.092 17 - 20 age 19 × 20 age conclusions : clinical interpretation of aerobic capacity impairment is influenced by aging in hf patients . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 4 interpretation 2 : 10 influenced 2 : 16 . 3 clinical 4 interpretation 4 interpretation 5 of 4 interpretation 9 is 5 of 8 impairment 6 aerobic 7 capacity 7 capacity 8 impairment 9 is 10 influenced 10 influenced 11 by 11 by 12 aging 12 aging 13 in 13 in 15 patients 14 hf 15 patients this evidence must be considered when using peak vo ( 2 ) for prognostic stratification and clinical decision - making in patients with hf [under] [b] - blocker therapy . 0 ###LEFT-WALL### 2 evidence 0 ###LEFT-WALL### 5 considered 0 ###LEFT-WALL### 27 - 0 ###LEFT-WALL### 28 blocker 0 ###LEFT-WALL### 30 . 1 this 2 evidence 2 evidence 3 must 3 must 4 be 4 be 5 considered 5 considered 6 when 5 considered 20 making 6 when 7 using 7 using 9 vo 7 using 13 for 8 peak 9 vo 9 vo 11 2 10 ( 11 2 11 2 12 ) 13 for 16 and 14 prognostic 15 stratification 15 stratification 16 and 16 and 18 decision 17 clinical 18 decision 19 - 20 making 20 making 21 in 20 making 22 patients 20 making 23 with 20 making 27 - 23 with 24 hf 27 - 28 blocker 28 blocker 29 therapy background and aims : a large body of evidence indicates that cerebral hypoperfusion is one of the earliest signs in the development of alzheimer 's disease ( ad ) . 0 ###LEFT-WALL### 3 aims 0 ###LEFT-WALL### 4 : 0 ###LEFT-WALL### 30 . 1 background 2 and 2 and 3 aims 4 : 7 body 4 : 10 indicates 5 a 7 body 6 large 7 body 7 body 8 of 7 body 10 indicates 8 of 9 evidence 10 indicates 11 that 11 that 13 hypoperfusion 11 that 14 is 12 cerebral 13 hypoperfusion 13 hypoperfusion 14 is 14 is 15 one 15 one 16 of 15 one 23 of 16 of 19 signs 17 the 18 earliest 17 the 19 signs 19 signs 20 in 20 in 22 development 21 the 22 development 23 of 26 disease 24 alzheimer 25 's 25 's 26 disease 26 disease 28 ad 27 ( 28 ad 28 ad 29 ) the aim of our study was to evaluate whether the brain reperfusion rehabilitation therapy ( brrt ) would improve verbal memory and learning [and/or] global cognitive impairment in mild ad . 0 ###LEFT-WALL### 2 aim 0 ###LEFT-WALL### 31 . 1 the 2 aim 2 aim 3 of 2 aim 6 was 3 of 5 study 4 our 5 study 6 was 7 to 6 was 8 evaluate 7 to 8 evaluate 8 evaluate 9 whether 9 whether 14 therapy 9 whether 19 improve 10 the 14 therapy 11 brain 14 therapy 12 reperfusion 14 therapy 13 rehabilitation 14 therapy 14 therapy 16 brrt 14 therapy 18 would 15 ( 16 brrt 16 brrt 17 ) 18 would 19 improve 19 improve 22 and 19 improve 28 in 20 verbal 21 memory 21 memory 22 and 22 and 27 impairment 23 learning 27 impairment 25 global 27 impairment 26 cognitive 27 impairment 28 in 30 ad 29 mild 30 ad at baseline ( t0 ) , and at the end of the 3 months ( t3 ) , 6 months ( t6 ) and 12 months ( t12 ) participants from both groups were given an evaluation , using mini - mental state examination ( mmse ) and rey auditory verbal learning test ( ravlt ) . 0 ###LEFT-WALL### 30 participants 0 ###LEFT-WALL### 35 given 0 ###LEFT-WALL### 41 - 0 ###LEFT-WALL### 57 . 1 at 2 baseline 1 at 7 and 2 baseline 4 t0 3 ( 4 t0 4 t0 5 ) 6 , 7 and 7 and 8 at 7 and 29 ) 7 and 30 participants 8 at 24 and 9 the 10 end 10 end 11 of 10 end 18 , 11 of 14 months 12 the 13 3 13 3 14 months 14 months 16 t3 15 ( 16 t3 16 t3 17 ) 18 , 20 months 18 , 24 and 19 6 20 months 20 months 22 t6 21 ( 22 t6 22 t6 23 ) 24 and 26 months 25 12 26 months 26 months 28 t12 27 ( 28 t12 28 t12 29 ) 30 participants 31 from 30 participants 34 were 31 from 33 groups 32 both 33 groups 34 were 35 given 35 given 37 evaluation 35 given 39 using 36 an 37 evaluation 38 , 39 using 39 using 40 mini 39 using 41 - 41 - 48 and 42 mental 43 state 43 state 44 examination 44 examination 46 mmse 45 ( 46 mmse 46 mmse 47 ) 46 mmse 48 and 48 and 55 ravlt 49 rey 50 auditory 50 auditory 51 verbal 51 verbal 52 learning 52 learning 53 test 53 test 55 ravlt 54 ( 55 ravlt 55 ravlt 56 ) in both groups by using near - infrared spectroscopy , at t0 and t12 , we measured tissue oxygen saturation ( toi ) on temporal - parietal and frontal cortex of both sides . 0 ###LEFT-WALL### 16 we 0 ###LEFT-WALL### 17 measured 0 ###LEFT-WALL### 34 . 1 in 3 groups 1 in 16 we 2 both 3 groups 3 groups 4 by 4 by 5 using 5 using 9 spectroscopy 6 near 7 - 6 near 9 spectroscopy 8 infrared 9 spectroscopy 9 spectroscopy 11 at 10 , 11 at 11 at 13 and 11 at 15 , 12 t0 13 and 13 and 14 t12 16 we 17 measured 17 measured 20 saturation 17 measured 24 on 18 tissue 20 saturation 19 oxygen 20 saturation 20 saturation 22 toi 21 ( 22 toi 22 toi 23 ) 24 on 33 sides 25 temporal 26 - 25 temporal 33 sides 27 parietal 28 and 28 and 30 cortex 28 and 31 of 28 and 33 sides 29 frontal 30 cortex 31 of 32 both results : ten patients from the brrt group and 10 from the control group completed the 12 - [month] follow - up . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 4 patients 2 : 8 group 2 : 9 and 2 : 18 - 3 ten 4 patients 4 patients 5 from 4 patients 8 group 5 from 7 brrt 6 the 7 brrt 9 and 10 10 9 and 15 completed 10 10 11 from 10 10 15 completed 11 from 14 group 12 the 14 group 13 control 14 group 15 completed 17 12 16 the 17 12 18 - 20 follow 20 follow 22 up 21 - 22 up 22 up 23 . at the end of rehabilitation protocol , a significant improvement of mmse and ravlt was observed in the brrt group as compared [to] control group . 0 ###LEFT-WALL### 10 improvement 0 ###LEFT-WALL### 16 observed 0 ###LEFT-WALL### 26 . 1 at 3 end 1 at 7 , 1 at 10 improvement 2 the 3 end 3 end 4 of 4 of 6 protocol 5 rehabilitation 6 protocol 8 a 10 improvement 9 significant 10 improvement 10 improvement 11 of 10 improvement 15 was 11 of 14 ravlt 12 mmse 13 and 13 and 14 ravlt 15 was 16 observed 16 observed 17 in 17 in 25 group 18 the 25 group 19 brrt 20 group 20 group 25 group 21 as 22 compared 22 compared 24 control 24 control 25 group at t12 compared to t0 , a significant improvement of toi on frontal cortex [of] [both] sides was observed in the brrt group as compared to [control] group . 0 ###LEFT-WALL### 9 improvement 0 ###LEFT-WALL### 25 compared 0 ###LEFT-WALL### 29 . 1 at 2 t12 1 at 6 , 1 at 9 improvement 2 t12 3 compared 3 compared 4 to 4 to 5 t0 7 a 8 significant 7 a 9 improvement 8 significant 9 improvement 9 improvement 10 of 9 improvement 18 was 10 of 11 toi 11 toi 12 on 12 on 17 sides 13 frontal 14 cortex 14 cortex 17 sides 18 was 19 observed 19 observed 20 in 19 observed 24 as 20 in 23 group 21 the 23 group 22 brrt 23 group 24 as 25 compared 25 compared 26 to 26 to 28 group conclusion : brrt improves verbal memory - learning and global cognitive impairment which are associated with increased toi values on frontal cortex [of] [both] sides . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 26 . 2 : 3 brrt 2 : 4 improves 2 : 7 - 3 brrt 4 improves 4 improves 6 memory 5 verbal 6 memory 7 - 9 and 8 learning 9 and 9 and 12 impairment 9 and 13 which 9 and 14 are 10 global 12 impairment 11 cognitive 12 impairment 13 which 14 are 14 are 15 associated 15 associated 16 with 16 with 19 values 17 increased 19 values 18 toi 19 values 19 values 20 on 20 on 25 sides 21 frontal 25 sides 22 cortex 25 sides declines in muscle size and strength are commonly reported as a consequence of aging ; however , few studies have investigated the influence of aging on the rate of muscle activation and rapid force characteristics across the lifespan . 0 ###LEFT-WALL### 1 declines 0 ###LEFT-WALL### 15 ; 0 ###LEFT-WALL### 21 investigated 0 ###LEFT-WALL### 39 . 1 declines 2 in 1 declines 5 and 1 declines 13 of 1 declines 14 aging 2 in 3 muscle 4 size 5 and 5 and 6 strength 5 and 7 are 7 are 9 reported 8 commonly 9 reported 9 reported 10 as 10 as 12 consequence 11 a 12 consequence 12 consequence 13 of 14 aging 15 ; 15 ; 19 studies 16 however 17 , 16 however 19 studies 18 few 19 studies 19 studies 20 have 20 have 21 investigated 21 investigated 23 influence 21 investigated 26 on 21 investigated 36 across 22 the 23 influence 23 influence 24 of 24 of 25 aging 26 on 32 and 27 the 28 rate 28 rate 29 of 28 rate 32 and 29 of 31 activation 30 muscle 31 activation 32 and 35 characteristics 33 rapid 35 characteristics 34 force 35 characteristics 36 across 38 lifespan 37 the 38 lifespan this study aims to investigate the effects of aging on the rate of muscle activation and rapid force characteristics of the plantar flexors . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 aims 0 ###LEFT-WALL### 24 . 1 this 2 study 2 study 3 aims 3 aims 4 to 3 aims 5 investigate 4 to 5 investigate 5 investigate 7 effects 5 investigate 10 on 6 the 7 effects 7 effects 8 of 8 of 9 aging 10 on 12 rate 11 the 12 rate 12 rate 13 of 12 rate 20 of 13 of 16 and 14 muscle 15 activation 15 activation 16 and 16 and 19 characteristics 17 rapid 18 force 18 force 19 characteristics 20 of 23 flexors 21 the 23 flexors 22 plantar 23 flexors the old men exhibited lower pf ( 30.7 % [and] 27.6 % lower , respectively ) and absolute ( 24.4 - 55.1 % ) and relative ( 16.4 - 28.9 % ) rfd values compared to the young and middle - aged men ( [p] ≤ 0.03 ) . 0 ###LEFT-WALL### 3 men 0 ###LEFT-WALL### 5 lower 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 49 . 1 the 3 men 2 old 3 men 3 men 4 exhibited 3 men 5 lower 5 lower 6 pf 6 pf 9 % 7 ( 9 % 8 30.7 9 % 9 % 12 % 9 % 13 lower 9 % 16 ) 11 27.6 12 % 12 % 13 lower 13 lower 15 respectively 14 , 15 respectively 15 respectively 16 ) 17 and 34 values 17 and 35 compared 18 absolute 21 - 18 absolute 25 and 19 ( 21 - 20 24.4 21 - 21 - 23 % 21 - 24 ) 22 55.1 23 % 25 and 26 relative 25 and 34 values 26 relative 29 - 27 ( 29 - 28 16.4 29 - 29 - 31 % 29 - 32 ) 30 28.9 31 % 33 rfd 34 values 34 values 35 compared 35 compared 36 to 36 to 39 and 37 the 38 young 38 young 39 and 39 and 40 middle 39 and 43 men 41 - 43 men 42 aged 43 men 43 men 46 ≤ 43 men 48 ) 44 ( 46 ≤ 46 ≤ 47 0.03 46 ≤ 48 ) rer values were similar between the young and old men [(] p ≥ 0.30 [ )( [however] , rer values were greater for the middle - aged [men] when compared to the young and old men for the soleus ( p [<] [0.01] [ )(and the old men for the medial gastrocnemius ( [p] ≤ 0.02 ) . 1 rer 2 values 1 rer 3 were 1 rer 4 similar 1 rer 5 between 1 rer 13 ≥ 2 values 3 were 5 between 8 and 6 the 7 young 7 young 8 and 8 and 10 men 9 old 10 men 10 men 12 p 13 ≥ 14 0.30 14 0.30 26 - 18 , 26 - 19 rer 20 values 19 rer 21 were 19 rer 22 greater 19 rer 26 - 20 values 21 were 22 greater 23 for 23 for 25 middle 24 the 25 middle 26 - 36 men 27 aged 29 when 27 aged 31 to 27 aged 34 and 29 when 30 compared 31 to 33 young 32 the 33 young 34 and 35 old 34 and 36 men 36 men 37 for 37 for 39 soleus 38 the 39 soleus 39 soleus 48 men 40 ( 48 men 41 p 45 )(and 45 )(and 47 old 45 )(and 48 men 46 the 47 old 48 men 49 for 48 men 55 ≤ 48 men 58 . 49 for 52 gastrocnemius 50 the 52 gastrocnemius 51 medial 52 gastrocnemius 53 ( 55 ≤ 55 ≤ 56 0.02 55 ≤ 57 ) likewise [,] rfd/pf ratios were similar between young and old men ( [p] ≥ 0.26 ) [;] however [,] these ratios were greater for the middle - aged men at early [(] [p] ≤ 0.03 ) , but not later [(] [p] ≥ 0.10 [ )(, time intervals . 0 ###LEFT-WALL### 4 ratios 0 ###LEFT-WALL### 5 were 1 likewise 4 ratios 3 rfd/pf 4 ratios 4 ratios 5 were 5 were 6 similar 6 similar 7 between 6 similar 18 however 7 between 9 and 8 young 9 and 9 and 11 men 9 and 14 ≥ 10 old 11 men 12 ( 14 ≥ 14 ≥ 15 0.26 14 ≥ 16 ) 18 however 21 ratios 18 however 22 were 20 these 21 ratios 21 ratios 22 were 22 were 23 greater 23 greater 24 for 24 for 26 middle 25 the 26 middle 26 middle 29 men 26 middle 38 but 27 - 29 men 28 aged 29 men 29 men 30 at 29 men 36 ) 30 at 34 ≤ 31 early 34 ≤ 34 ≤ 35 0.03 37 , 38 but 38 but 39 not 38 but 43 ≥ 38 but 49 . 40 later 43 ≥ 43 ≥ 44 0.10 43 ≥ 48 intervals 46 )(, 48 intervals 47 time 48 intervals 48 intervals 49 . the lower pf and absolute and relative rfd values for the old men may contribute to the increased functional limitations often observed in older adults . 0 ###LEFT-WALL### 3 pf 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 26 . 1 the 3 pf 2 lower 3 pf 4 and 9 values 4 and 15 contribute 5 absolute 6 and 6 and 7 relative 6 and 9 values 8 rfd 9 values 9 values 10 for 9 values 14 may 10 for 13 men 11 the 13 men 12 old 13 men 14 may 15 contribute 15 contribute 16 to 16 to 20 limitations 17 the 20 limitations 18 increased 20 limitations 19 functional 20 limitations 20 limitations 22 observed 21 often 22 observed 22 observed 23 in 23 in 25 adults 24 older 25 adults interestingly , higher rates of muscle activation and greater early rfd/pf ratios in middle [-] aged men may be a reflection of physiological alterations in the neuromuscular system occurring in the fifth decade . 0 ###LEFT-WALL### 4 rates 0 ###LEFT-WALL### 19 be 0 ###LEFT-WALL### 34 . 1 interestingly 2 , 1 interestingly 4 rates 3 higher 4 rates 4 rates 5 of 4 rates 13 in 4 rates 18 may 5 of 8 and 6 muscle 7 activation 7 activation 8 and 8 and 12 ratios 9 greater 12 ratios 10 early 12 ratios 11 rfd/pf 12 ratios 13 in 17 men 14 middle 16 aged 16 aged 17 men 18 may 19 be 19 be 21 reflection 20 a 21 reflection 21 reflection 22 of 22 of 24 alterations 23 physiological 24 alterations 24 alterations 25 in 24 alterations 29 occurring 25 in 28 system 26 the 28 system 27 neuromuscular 28 system 29 occurring 30 in 30 in 33 decade 31 the 32 fifth 31 the 33 decade research into the use of clozapine in older people is somewhat scarce . 0 ###LEFT-WALL### 1 research 0 ###LEFT-WALL### 10 is 0 ###LEFT-WALL### 13 . 1 research 2 into 1 research 10 is 2 into 4 use 3 the 4 use 4 use 5 of 5 of 6 clozapine 6 clozapine 7 in 7 in 9 people 8 older 9 people 10 is 12 scarce 11 somewhat 12 scarce clozapine is associated with serious adverse effects such as agranulocytosis , seizures , myocarditis and metabolic syndrome . 0 ###LEFT-WALL### 1 clozapine 0 ###LEFT-WALL### 3 associated 0 ###LEFT-WALL### 18 . 1 clozapine 2 is 2 is 3 associated 3 associated 4 with 4 with 7 effects 5 serious 7 effects 6 adverse 7 effects 7 effects 9 as 8 such 9 as 9 as 15 and 10 agranulocytosis 11 , 11 , 12 seizures 11 , 13 , 13 , 14 myocarditis 13 , 15 and 15 and 17 syndrome 16 metabolic 17 syndrome other common undesirable effects such as sedation , constipation ( which can be fatal ) , urinary incontinence and hypersalivation further limit its use . 0 ###LEFT-WALL### 19 and 0 ###LEFT-WALL### 22 limit 0 ###LEFT-WALL### 25 . 1 other 4 effects 2 common 4 effects 3 undesirable 4 effects 4 effects 6 as 4 effects 16 , 5 such 6 as 6 as 7 sedation 7 sedation 9 constipation 8 , 9 constipation 9 constipation 11 which 9 constipation 15 ) 10 ( 11 which 11 which 12 can 11 which 15 ) 12 can 13 be 13 be 14 fatal 16 , 18 incontinence 16 , 19 and 17 urinary 18 incontinence 19 and 20 hypersalivation 19 and 22 limit 21 further 22 limit 22 limit 24 use 23 its 24 use these adverse effects are particularly important for the use of clozapine in older people , who are generally more susceptible to medication - related adverse effects . 0 ###LEFT-WALL### 3 effects 0 ###LEFT-WALL### 4 are 0 ###LEFT-WALL### 24 related 1 these 3 effects 2 adverse 3 effects 3 effects 4 are 4 are 5 particularly 4 are 6 important 6 important 7 for 6 important 12 in 7 for 9 use 8 the 9 use 9 use 10 of 10 of 11 clozapine 12 in 14 people 13 older 14 people 14 people 16 who 15 , 16 who 16 who 17 are 16 who 23 - 17 are 18 generally 17 are 20 susceptible 19 more 20 susceptible 20 susceptible 21 to 21 to 22 medication 23 - 24 related 24 related 26 effects 24 related 27 . 25 adverse 26 effects whilst clozapine should be used with caution in elderly people , strict monitoring procedures can help to prevent harmful effects through early detection , and certain management techniques exist to minimise them . 0 ###LEFT-WALL### 14 procedures 0 ###LEFT-WALL### 16 help 0 ###LEFT-WALL### 25 and 0 ###LEFT-WALL### 31 minimise 0 ###LEFT-WALL### 33 . 1 whilst 2 clozapine 1 whilst 5 used 1 whilst 11 , 1 whilst 14 procedures 2 clozapine 3 should 3 should 4 be 4 be 5 used 5 used 6 with 5 used 8 in 6 with 7 caution 8 in 10 people 9 elderly 10 people 12 strict 14 procedures 13 monitoring 14 procedures 14 procedures 15 can 15 can 16 help 16 help 17 to 16 help 18 prevent 17 to 18 prevent 18 prevent 20 effects 18 prevent 21 through 19 harmful 20 effects 21 through 23 detection 22 early 23 detection 24 , 25 and 25 and 28 techniques 25 and 29 exist 26 certain 27 management 27 management 28 techniques 28 techniques 29 exist 29 exist 30 to 30 to 31 minimise 31 minimise 32 them this review outlines the epidemiology of clozapine - related adverse effects in older people and discusses potential prevention and management strategies . 0 ###LEFT-WALL### 2 review 0 ###LEFT-WALL### 3 outlines 0 ###LEFT-WALL### 8 - 0 ###LEFT-WALL### 22 . 1 this 2 review 2 review 3 outlines 3 outlines 5 epidemiology 4 the 5 epidemiology 5 epidemiology 6 of 6 of 7 clozapine 8 - 15 and 9 related 11 effects 9 related 12 in 9 related 15 and 10 adverse 11 effects 12 in 14 people 13 older 14 people 15 and 16 discusses 16 discusses 19 and 17 potential 18 prevention 18 prevention 19 and 19 and 21 strategies 20 management 21 strategies vitamin d deficiency is the most under [-] diagnosed medical condition in postmenopausal women . 0 ###LEFT-WALL### 3 deficiency 0 ###LEFT-WALL### 4 is 0 ###LEFT-WALL### 15 . 1 vitamin 2 d 1 vitamin 3 deficiency 3 deficiency 4 is 4 is 6 most 5 the 6 most 6 most 7 under 7 under 11 condition 9 diagnosed 11 condition 10 medical 11 condition 11 condition 12 in 12 in 14 women 13 postmenopausal 14 women there are few epidemiologic studies on vitamin d status of postmenopausal women in iran . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 are 0 ###LEFT-WALL### 15 . 1 there 2 are 2 are 5 studies 3 few 5 studies 4 epidemiologic 5 studies 5 studies 6 on 6 on 9 status 7 vitamin 8 d 7 vitamin 9 status 9 status 10 of 10 of 12 women 11 postmenopausal 12 women 12 women 13 in 13 in 14 iran this study aimed to investigate the 25 - hydroxyvitamin d levels in postmenopausal women living in tehran , capital of iran . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 aimed 1 this 2 study 2 study 3 aimed 3 aimed 4 to 3 aimed 5 investigate 4 to 5 investigate 5 investigate 7 25 6 the 7 25 7 25 11 levels 7 25 19 capital 8 - 11 levels 9 hydroxyvitamin 10 d 9 hydroxyvitamin 11 levels 11 levels 12 in 11 levels 15 living 11 levels 18 , 12 in 14 women 13 postmenopausal 14 women 15 living 16 in 16 in 17 tehran 18 , 19 capital 19 capital 20 of 19 capital 22 . 20 of 21 iran in this cross sectional study , 110 women were selected via convenience sampling method from menopause clinic [of] tehran women general hospital between 2011 and 2012 . 0 ###LEFT-WALL### 8 women 0 ###LEFT-WALL### 10 selected 0 ###LEFT-WALL### 27 . 1 in 5 study 1 in 6 , 1 in 8 women 2 this 5 study 3 cross 5 study 4 sectional 5 study 7 110 8 women 8 women 9 were 9 were 10 selected 10 selected 11 via 11 via 12 convenience 12 convenience 13 sampling 13 sampling 14 method 14 method 15 from 15 from 22 hospital 16 menopause 21 general 17 clinic 21 general 19 tehran 20 women 20 women 21 general 21 general 22 hospital 22 hospital 25 and 23 between 25 and 24 2011 25 and 25 and 26 2012 for each woman , a questionnaire was completed , and 25 - hydroxyvitamin d levels were determined by chemiluminescence 's [immunoassay] . 0 ###LEFT-WALL### 6 questionnaire 0 ###LEFT-WALL### 8 completed 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 22 . 1 for 3 woman 1 for 4 , 1 for 6 questionnaire 2 each 3 woman 5 a 6 questionnaire 6 questionnaire 7 was 7 was 8 completed 9 , 10 and 10 and 11 25 10 and 12 - 11 25 12 - 12 - 15 levels 13 hydroxyvitamin 14 d 13 hydroxyvitamin 15 levels 15 levels 16 were 16 were 17 determined 17 determined 18 by 18 by 20 's 19 chemiluminescence 20 's vitamin d deficiency has been considered as a 25 ( oh )d of less than 20 [ng] / ml . 0 ###LEFT-WALL### 3 deficiency 0 ###LEFT-WALL### 6 considered 0 ###LEFT-WALL### 20 . 1 vitamin 2 d 1 vitamin 3 deficiency 3 deficiency 4 has 4 has 5 been 5 been 6 considered 6 considered 7 as 7 as 11 oh 8 a 11 oh 9 25 11 oh 10 ( 11 oh 11 oh 12 )d 11 oh 13 of 13 of 19 ml 14 less 15 than 15 than 16 20 16 20 19 ml 18 / 19 ml vitamin d insufficiency has been defined as a 25 ( oh )d of 21 - 29 ng / ml , and sufficiency as a 25 ( oh )d of 30 - 100 ng / ml . 0 ###LEFT-WALL### 3 insufficiency 0 ###LEFT-WALL### 6 defined 0 ###LEFT-WALL### 36 . 1 vitamin 2 d 1 vitamin 3 insufficiency 3 insufficiency 4 has 4 has 5 been 5 been 6 defined 6 defined 7 as 6 defined 23 as 7 as 21 and 8 a 11 oh 9 25 11 oh 10 ( 11 oh 11 oh 12 )d 11 oh 13 of 11 oh 21 and 13 of 19 ml 14 21 15 - 15 - 16 29 15 - 19 ml 16 29 17 ng 17 ng 18 / 20 , 21 and 21 and 22 sufficiency 23 as 27 oh 24 a 27 oh 25 25 27 oh 26 ( 27 oh 27 oh 28 )d 27 oh 29 of 29 of 35 ml 30 30 31 - 31 - 32 100 31 - 35 ml 32 100 33 ng 33 ng 34 / the data was analyzed by using pearson correlation test [in] spss version 16 . 0 ###LEFT-WALL### 2 data 0 ###LEFT-WALL### 4 analyzed 0 ###LEFT-WALL### 14 . 1 the 2 data 2 data 3 was 3 was 4 analyzed 4 analyzed 5 by 5 by 6 using 6 using 12 version 7 pearson 12 version 8 correlation 12 version 9 test 12 version 11 spss 12 version 12 version 13 16 the mean age of women was 52.67±5 years . 0 ###LEFT-WALL### 3 age 0 ###LEFT-WALL### 6 was 0 ###LEFT-WALL### 9 . 1 the 3 age 2 mean 3 age 3 age 4 of 3 age 6 was 4 of 5 women 6 was 8 years 7 52.67±5 8 years the mean age [at] natural menopause onset was 47.66±4.44 years , and the median menopause age was 49.00 . 0 ###LEFT-WALL### 7 onset 0 ###LEFT-WALL### 8 was 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 19 . 1 the 7 onset 2 mean 7 onset 3 age 7 onset 5 natural 6 menopause 6 menopause 7 onset 7 onset 8 was 8 was 10 years 9 47.66±4.44 10 years 11 , 12 and 12 and 16 age 12 and 17 was 13 the 16 age 14 median 16 age 15 menopause 16 age 16 age 17 was 17 was 18 49.00 the median 25 ( oh )d level was 19.28 ( [inter] quartile range=26.08 ) . 0 ###LEFT-WALL### 7 level 0 ###LEFT-WALL### 8 was 0 ###LEFT-WALL### 15 . 1 the 7 level 2 median 7 level 3 25 5 oh 4 ( 5 oh 5 oh 6 )d 5 oh 7 level 7 level 8 was 8 was 9 19.28 9 19.28 13 range=26.08 10 ( 13 range=26.08 12 quartile 13 range=26.08 13 range=26.08 14 ) we found vitamin d deficiency and vitamin d insufficiency 52.7 % and17.3 [%] respectively . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 found 0 ###LEFT-WALL### 15 . 1 we 2 found 2 found 3 vitamin 2 found 5 deficiency 2 found 6 and 2 found 14 respectively 3 vitamin 4 d 6 and 7 vitamin 6 and 12 and17.3 7 vitamin 8 d 9 insufficiency 12 and17.3 10 52.7 11 % 11 % 12 and17.3 serum 25 ( oh ) [d] concentrations were significantly correlated with age ( r=0.21 , p=0.024 ) . 0 ###LEFT-WALL### 7 concentrations 0 ###LEFT-WALL### 10 correlated 0 ###LEFT-WALL### 18 . 1 serum 2 25 1 serum 4 oh 3 ( 4 oh 4 oh 5 ) 4 oh 7 concentrations 7 concentrations 8 were 8 were 10 correlated 9 significantly 10 correlated 10 correlated 11 with 11 with 12 age 12 age 14 r=0.21 12 age 16 p=0.024 13 ( 14 r=0.21 14 r=0.21 15 , 15 , 16 p=0.024 16 p=0.024 17 ) these findings indicate that 25 ( oh )d level in postmenopausal women from tehran is low . 0 ###LEFT-WALL### 2 findings 0 ###LEFT-WALL### 3 indicate 0 ###LEFT-WALL### 17 . 1 these 2 findings 2 findings 3 indicate 3 indicate 4 that 4 that 9 level 4 that 15 is 5 25 7 oh 6 ( 7 oh 7 oh 8 )d 7 oh 9 level 9 level 10 in 9 level 15 is 10 in 12 women 11 postmenopausal 12 women 12 women 13 from 13 from 14 tehran 15 is 16 low there is a statistically significant positive correlation between vitamin d concentration and age in late postmenopausal period . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 18 . 1 there 2 is 2 is 7 correlation 3 a 4 statistically 3 a 7 correlation 4 statistically 5 significant 5 significant 7 correlation 6 positive 7 correlation 7 correlation 8 between 8 between 12 and 9 vitamin 10 d 9 vitamin 11 concentration 11 concentration 12 and 12 and 13 age 12 and 14 in 14 in 17 period 15 late 17 period 16 postmenopausal 17 period minimally invasive glaucoma surgeries ( migs ) can improve the conventional , pressure - dependent outflow by bypassing [or] ablating the trabecular meshwork ( tm ) , or creating alternative drainage routes into the suprachoroidal or subconjunctival space . 0 ###LEFT-WALL### 4 surgeries 0 ###LEFT-WALL### 39 . 1 minimally 4 surgeries 2 invasive 3 glaucoma 3 glaucoma 4 surgeries 4 surgeries 6 migs 4 surgeries 8 can 5 ( 6 migs 6 migs 7 ) 8 can 9 improve 9 improve 28 or 9 improve 33 into 10 the 16 outflow 11 conventional 13 pressure 11 conventional 15 dependent 12 , 13 pressure 13 pressure 14 - 15 dependent 16 outflow 16 outflow 17 by 16 outflow 20 ablating 16 outflow 28 or 17 by 18 bypassing 20 ablating 23 meshwork 21 the 23 meshwork 22 trabecular 23 meshwork 23 meshwork 25 tm 24 ( 25 tm 25 tm 26 ) 27 , 28 or 28 or 32 routes 29 creating 31 drainage 30 alternative 31 drainage 31 drainage 32 routes 33 into 38 space 34 the 38 space 35 suprachoroidal 36 or 36 or 37 subconjunctival 36 or 38 space they have a highly favourable risk profile compared to penetrating surgeries , and lower intraocular pressure with variable efficacy that may depend on the extent of outflow segments accessed . 0 ###LEFT-WALL### 1 they 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 30 . 1 they 13 and 2 have 7 profile 2 have 13 and 3 a 4 highly 3 a 7 profile 4 highly 5 favourable 5 favourable 7 profile 6 risk 7 profile 7 profile 8 compared 7 profile 9 to 9 to 10 penetrating 10 penetrating 11 surgeries 12 , 13 and 13 and 14 lower 13 and 17 with 14 lower 16 pressure 15 intraocular 16 pressure 17 with 19 efficacy 18 variable 19 efficacy 19 efficacy 20 that 19 efficacy 21 may 20 that 21 may 21 may 22 depend 22 depend 23 on 23 on 25 extent 24 the 25 extent 25 extent 26 of 26 of 28 segments 27 outflow 28 segments 28 segments 29 accessed since they are highly standardised procedures that use clear corneal incisions , they can elegantly be combined with cataract [and] refractive procedures to improve vision in the same session . 0 ###LEFT-WALL### 13 they 0 ###LEFT-WALL### 17 combined 0 ###LEFT-WALL### 30 . 1 since 2 they 1 since 3 are 1 since 12 , 1 since 13 they 2 they 3 are 3 are 6 procedures 4 highly 5 standardised 5 standardised 6 procedures 6 procedures 7 that 6 procedures 8 use 7 that 8 use 8 use 11 incisions 9 clear 11 incisions 10 corneal 11 incisions 13 they 14 can 14 can 16 be 15 elegantly 16 be 16 be 17 combined 17 combined 18 with 17 combined 23 to 18 with 22 procedures 19 cataract 22 procedures 21 refractive 22 procedures 23 to 24 improve 24 improve 25 vision 24 improve 26 in 26 in 29 session 27 the 28 same 28 same 29 session there is a growing need for surgeons to become proficient in migs to address the increasing prevalence of glaucoma and cataracts in a well - informed , aging population . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 14 address 0 ###LEFT-WALL### 30 . 1 there 2 is 2 is 5 need 2 is 10 proficient 3 a 5 need 4 growing 5 need 5 need 6 for 6 for 7 surgeons 7 surgeons 8 to 7 surgeons 9 become 8 to 9 become 10 proficient 11 in 10 proficient 13 to 11 in 12 migs 13 to 14 address 14 address 17 prevalence 15 the 17 prevalence 16 increasing 17 prevalence 17 prevalence 18 of 17 prevalence 28 aging 18 of 20 and 19 glaucoma 20 and 20 and 21 cataracts 20 and 22 in 22 in 24 well 23 a 24 well 24 well 26 informed 25 - 26 informed 26 informed 27 , 28 aging 29 population techniques of visualisation and instrumentation in an anatomically highly confined space with semitransparent tissues are fundamentally different from other anterior segment surgeries , and present even experienced surgeons with a substantial learning curve . 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 15 are 0 ###LEFT-WALL### 34 . 1 techniques 2 of 1 techniques 4 and 2 of 3 visualisation 4 and 5 instrumentation 4 and 6 in 4 and 15 are 6 in 11 space 7 an 8 anatomically 7 an 11 space 8 anatomically 10 confined 9 highly 10 confined 10 confined 11 space 11 space 12 with 12 with 14 tissues 13 semitransparent 14 tissues 15 are 16 fundamentally 15 are 28 surgeons 17 different 18 from 17 different 24 and 18 from 22 surgeries 19 other 22 surgeries 20 anterior 21 segment 21 segment 22 surgeries 23 , 24 and 24 and 25 present 24 and 28 surgeons 26 even 27 experienced 27 experienced 28 surgeons 28 surgeons 29 with 29 with 33 curve 30 a 33 curve 31 substantial 33 curve 32 learning 33 curve here , we provide practical tips , and review techniques and outcomes of tm bypass and ablation migs . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 provide 0 ###LEFT-WALL### 19 . 1 here 2 , 1 here 3 we 3 we 4 provide 4 provide 16 and 5 practical 6 tips 6 tips 8 and 7 , 8 and 8 and 9 review 8 and 11 and 8 and 15 bypass 8 and 16 and 10 techniques 11 and 11 and 12 outcomes 11 and 13 of 11 and 15 bypass 13 of 14 tm 16 and 18 migs 17 ablation 18 migs many sensory and cognitive changes accompany normal ageing , including changes to visual attention . 0 ###LEFT-WALL### 5 changes 0 ###LEFT-WALL### 6 accompany 1 many 5 changes 2 sensory 3 and 3 and 4 cognitive 3 and 5 changes 5 changes 6 accompany 6 accompany 8 ageing 7 normal 8 ageing 8 ageing 10 including 9 , 10 including 10 including 11 changes 10 including 12 to 10 including 15 . 12 to 14 attention 13 visual 14 attention several studies have investigated age - related changes in the control of attention to specific locations [(] spatial orienting ) , but it is unknown whether control over the distribution or breadth of attention ( spatial focus ) also changes with age . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 4 investigated 0 ###LEFT-WALL### 7 related 0 ###LEFT-WALL### 22 but 0 ###LEFT-WALL### 43 . 1 several 2 studies 2 studies 3 have 3 have 4 investigated 4 investigated 5 age 6 - 7 related 7 related 8 changes 7 related 20 ) 8 changes 9 in 8 changes 14 to 9 in 11 control 10 the 11 control 11 control 12 of 12 of 13 attention 14 to 19 orienting 15 specific 16 locations 16 locations 19 orienting 18 spatial 19 orienting 21 , 22 but 22 but 23 it 22 but 24 is 23 it 24 is 24 is 25 unknown 25 unknown 26 whether 26 whether 27 control 26 whether 40 changes 27 control 28 over 27 control 33 of 27 control 37 focus 27 control 40 changes 28 over 31 or 29 the 30 distribution 30 distribution 31 or 31 or 32 breadth 33 of 34 attention 35 ( 37 focus 36 spatial 37 focus 37 focus 38 ) 39 also 40 changes 40 changes 41 with 41 with 42 age in the present study , we employed a dual - stream attentional blink task and assessed changes to the spatial distribution of attention through the joint consequences of temporal [lag] and spatial separation on second [-] target accuracy . 0 ###LEFT-WALL### 6 we 0 ###LEFT-WALL### 15 and 0 ###LEFT-WALL### 39 . 1 in 4 study 1 in 5 , 1 in 6 we 2 the 4 study 3 present 4 study 6 we 15 and 7 employed 14 task 7 employed 15 and 8 a 14 task 9 dual 10 - 9 dual 14 task 11 stream 14 task 12 attentional 13 blink 13 blink 14 task 15 and 16 assessed 16 assessed 17 changes 16 assessed 18 to 16 assessed 24 through 16 assessed 34 on 18 to 21 distribution 19 the 21 distribution 20 spatial 21 distribution 21 distribution 22 of 22 of 23 attention 24 through 27 consequences 25 the 27 consequences 26 joint 27 consequences 27 consequences 28 of 28 of 31 and 29 temporal 31 and 31 and 33 separation 32 spatial 33 separation 34 on 38 accuracy 35 second 38 accuracy 37 target 38 accuracy experiment 1 compared the rate at which attention narrows in younger [(] mean age 22.6 , sd [4.25] ) and older [(] mean age 66.8 , sd [4.36] ) adults . 0 ###LEFT-WALL### 1 experiment 0 ###LEFT-WALL### 31 . 1 experiment 2 1 1 experiment 3 compared 3 compared 30 adults 4 the 5 rate 5 rate 6 at 5 rate 20 and 6 at 7 which 6 at 8 attention 6 at 9 narrows 8 attention 9 narrows 9 narrows 10 in 10 in 14 age 11 younger 13 mean 13 mean 14 age 14 age 15 22.6 14 age 17 sd 16 , 17 sd 17 sd 19 ) 20 and 24 age 20 and 27 sd 20 and 30 adults 21 older 23 mean 23 mean 24 age 24 age 25 66.8 26 , 27 sd 27 sd 29 ) the results showed that whereas young adults can narrow attention to one stream within 133 m [s] , older adults were unable to do the same within this time period . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 showed 0 ###LEFT-WALL### 31 . 1 the 2 results 2 results 3 showed 3 showed 4 that 4 that 20 adults 4 that 21 were 5 whereas 7 adults 5 whereas 9 narrow 5 whereas 18 , 5 whereas 20 adults 6 young 7 adults 7 adults 8 can 8 can 9 narrow 9 narrow 10 attention 9 narrow 11 to 9 narrow 14 within 11 to 13 stream 12 one 13 stream 14 within 16 m 15 133 16 m 19 older 20 adults 20 adults 21 were 21 were 22 unable 22 unable 23 to 22 unable 26 same 22 unable 27 within 23 to 24 do 25 the 26 same 27 within 30 period 28 this 30 period 29 time 30 period experiment 2 showed that older adults can narrow their attention to one stream when given more time ( 266 m [s] ) . 0 ###LEFT-WALL### 1 experiment 0 ###LEFT-WALL### 3 showed 0 ###LEFT-WALL### 23 . 1 experiment 2 2 1 experiment 3 showed 3 showed 4 that 4 that 6 adults 4 that 8 narrow 5 older 6 adults 6 adults 7 can 7 can 8 narrow 8 narrow 10 attention 8 narrow 11 to 8 narrow 14 when 9 their 10 attention 11 to 13 stream 12 one 13 stream 14 when 15 given 15 given 17 time 16 more 17 time 17 time 20 m 18 ( 20 m 19 266 20 m 20 m 22 ) experiment 3 confirmed that age - related changes in retinal illuminance did not account for delayed attentional narrowing in older adults . 0 ###LEFT-WALL### 1 experiment 0 ###LEFT-WALL### 3 confirmed 0 ###LEFT-WALL### 22 . 1 experiment 2 3 1 experiment 3 confirmed 3 confirmed 4 that 4 that 5 age 4 that 14 account 5 age 12 did 6 - 7 related 7 related 8 changes 7 related 9 in 7 related 12 did 9 in 11 illuminance 10 retinal 11 illuminance 12 did 13 not 12 did 14 account 14 account 15 for 14 account 19 in 15 for 18 narrowing 16 delayed 18 narrowing 17 attentional 18 narrowing 19 in 21 adults 20 older 21 adults considered together , these experiments demonstrate that older adults can narrow their attentional focus , but that they are delayed in initiating this process compared to younger adults . 0 ###LEFT-WALL### 5 experiments 0 ###LEFT-WALL### 6 demonstrate 0 ###LEFT-WALL### 15 , 0 ###LEFT-WALL### 29 . 1 considered 2 together 1 considered 3 , 1 considered 5 experiments 4 these 5 experiments 5 experiments 6 demonstrate 6 demonstrate 7 that 7 that 9 adults 7 that 11 narrow 8 older 9 adults 9 adults 10 can 10 can 11 narrow 11 narrow 14 focus 12 their 14 focus 13 attentional 14 focus 15 , 18 they 15 , 20 delayed 16 but 17 that 16 but 18 they 18 they 19 are 19 are 20 delayed 20 delayed 21 in 21 in 22 initiating 22 initiating 24 process 23 this 24 process 24 process 25 compared 25 compared 26 to 26 to 28 adults 27 younger 28 adults this finding adds to previously reported reductions in attentional dynamics , deficits in inhibitory processes , and reductions in posterior parietal cortex function that [accompany] normal ageing . 0 ###LEFT-WALL### 2 finding 0 ###LEFT-WALL### 3 adds 0 ###LEFT-WALL### 28 . 1 this 2 finding 2 finding 3 adds 3 adds 4 to 3 adds 8 in 3 adds 19 in 4 to 7 reductions 5 previously 6 reported 6 reported 7 reductions 8 in 17 and 9 attentional 10 dynamics 10 dynamics 11 , 11 , 12 deficits 11 , 17 and 12 deficits 13 in 13 in 15 processes 14 inhibitory 15 processes 16 , 17 and 17 and 18 reductions 19 in 27 ageing 20 posterior 22 cortex 21 parietal 22 cortex 22 cortex 27 ageing 23 function 27 ageing 24 that 26 normal 26 normal 27 ageing aging process or senescence affects the expression of a wide range of phenotypic traits throughout the life span of organisms . 0 ###LEFT-WALL### 1 aging 0 ###LEFT-WALL### 5 affects 0 ###LEFT-WALL### 21 . 1 aging 3 or 1 aging 5 affects 2 process 3 or 3 or 4 senescence 5 affects 7 expression 5 affects 15 throughout 6 the 7 expression 7 expression 8 of 8 of 11 range 9 a 10 wide 9 a 11 range 10 wide 11 range 11 range 12 of 12 of 14 traits 13 phenotypic 14 traits 15 throughout 18 span 16 the 18 span 17 life 18 span 18 span 19 of 19 of 20 organisms these traits often show modular , synergistic , and even antagonistic relationships , and [are] also influenced by genomic , developmental , physiological and environmental factors . 0 ###LEFT-WALL### 2 traits 0 ###LEFT-WALL### 14 and 0 ###LEFT-WALL### 27 . 1 these 2 traits 2 traits 14 and 3 often 4 show 4 show 12 relationships 4 show 14 and 5 modular 6 , 5 modular 12 relationships 7 synergistic 9 and 8 , 9 and 9 and 10 even 9 and 11 antagonistic 9 and 12 relationships 13 , 14 and 14 and 17 influenced 14 and 18 by 16 also 17 influenced 18 by 26 factors 19 genomic 20 , 19 genomic 26 factors 21 developmental 22 , 22 , 23 physiological 22 , 24 and 24 and 25 environmental 24 and 26 factors the cardiovascular system ( cvs ) [in] [humans] represents a major modular system in which the relationships among physiological , anatomical and morphological traits undergo continuous remodeling throughout the life span of an individual . 0 ###LEFT-WALL### 3 system 0 ###LEFT-WALL### 9 represents 0 ###LEFT-WALL### 35 . 1 the 3 system 2 cardiovascular 3 system 3 system 5 cvs 3 system 9 represents 4 ( 5 cvs 5 cvs 6 ) 9 represents 13 system 10 a 11 major 10 a 13 system 11 major 13 system 12 modular 13 system 13 system 14 in 14 in 15 which 14 in 17 relationships 14 in 25 undergo 16 the 17 relationships 17 relationships 18 among 17 relationships 25 undergo 18 among 24 traits 19 physiological 20 , 20 , 21 anatomical 20 , 22 and 22 and 23 morphological 22 and 24 traits 25 undergo 27 remodeling 25 undergo 28 throughout 26 continuous 27 remodeling 28 throughout 31 span 29 the 31 span 30 life 31 span 31 span 32 of 32 of 34 individual 33 an 34 individual here we extend the concept of developmental plasticity in order to study the relationships among 14 traits measured on 3,412 individuals from the framingham heart study cohort , relative to age and gender , using exploratory structural equation modeling - a form of systems analysis . 0 ###LEFT-WALL### 2 we 0 ###LEFT-WALL### 3 extend 1 here 2 we 2 we 3 extend 3 extend 5 concept 3 extend 9 in 3 extend 15 among 4 the 5 concept 5 concept 6 of 6 of 8 plasticity 7 developmental 8 plasticity 9 in 10 order 10 order 11 to 10 order 12 study 11 to 12 study 12 study 14 relationships 13 the 14 relationships 15 among 17 traits 16 14 17 traits 17 traits 18 measured 18 measured 19 on 18 measured 22 from 18 measured 35 using 19 on 21 individuals 20 3,412 21 individuals 22 from 27 cohort 23 the 27 cohort 24 framingham 25 heart 25 heart 26 study 26 study 27 cohort 27 cohort 32 and 28 , 32 and 29 relative 30 to 29 relative 32 and 30 to 31 age 32 and 33 gender 32 and 34 , 34 , 35 using 35 using 39 modeling 35 using 46 . 36 exploratory 38 equation 37 structural 38 equation 38 equation 39 modeling 39 modeling 42 form 40 - 42 form 41 a 42 form 42 form 43 of 42 form 46 . 43 of 45 analysis 44 systems 45 analysis our results reveal differing patterns of [association] among cardiac traits in younger and older persons in both sexes , indicating that physiological and developmental factors may be channeled differentially in relation to age and gender during the remodeling process . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 reveal 0 ###LEFT-WALL### 19 , 0 ###LEFT-WALL### 40 . 1 our 2 results 2 results 3 reveal 3 reveal 5 patterns 4 differing 5 patterns 5 patterns 6 of 6 of 8 among 8 among 10 traits 9 cardiac 10 traits 10 traits 11 in 11 in 15 persons 12 younger 13 and 13 and 14 older 13 and 15 persons 15 persons 16 in 16 in 18 sexes 17 both 18 sexes 19 , 20 indicating 19 , 28 channeled 20 indicating 21 that 20 indicating 27 be 21 that 23 and 21 that 26 may 22 physiological 23 and 23 and 25 factors 23 and 26 may 24 developmental 25 factors 27 be 28 channeled 28 channeled 29 differentially 28 channeled 32 to 30 in 31 relation 31 relation 32 to 32 to 34 and 33 age 34 and 34 and 35 gender 34 and 36 during 36 during 39 process 37 the 39 process 38 remodeling 39 process we suggest that systems approaches are necessary in order to understand the coordinated functional relationships among traits of the cvs over the life course of individuals . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 suggest 0 ###LEFT-WALL### 27 . 1 we 2 suggest 2 suggest 3 that 3 that 4 systems 3 that 11 understand 4 systems 5 approaches 4 systems 10 to 5 approaches 6 are 6 are 7 necessary 7 necessary 8 in 7 necessary 10 to 8 in 9 order 11 understand 15 relationships 11 understand 21 over 12 the 15 relationships 13 coordinated 15 relationships 14 functional 15 relationships 15 relationships 16 among 15 relationships 18 of 16 among 17 traits 18 of 20 cvs 19 the 20 cvs 21 over 24 course 22 the 24 course 23 life 24 course 24 course 25 of 25 of 26 individuals a possible negative effect of iron [overload] on bone metabolism has been suggested by the fact that patients with hemochromatosis , thalassemia , and sickle cell anemia have lower bone mineral density than the general population . 0 ###LEFT-WALL### 4 effect 0 ###LEFT-WALL### 13 suggested 0 ###LEFT-WALL### 37 . 1 a 4 effect 2 possible 4 effect 3 negative 4 effect 4 effect 5 of 4 effect 11 has 5 of 6 iron 6 iron 8 on 8 on 10 metabolism 9 bone 10 metabolism 11 has 12 been 12 been 13 suggested 13 suggested 14 by 14 by 16 fact 15 the 16 fact 16 fact 17 that 17 that 24 and 17 that 28 have 18 patients 19 with 18 patients 21 , 19 with 20 hemochromatosis 21 , 22 thalassemia 21 , 24 and 23 , 24 and 24 and 27 anemia 24 and 28 have 25 sickle 27 anemia 26 cell 27 anemia 28 have 32 density 28 have 33 than 29 lower 30 bone 30 bone 32 density 31 mineral 32 density 33 than 36 population 34 the 36 population 35 general 36 population however , the influence of iron [overload] on bone health in the general population is uncertain . 0 ###LEFT-WALL### 4 influence 0 ###LEFT-WALL### 15 is 0 ###LEFT-WALL### 17 . 1 however 2 , 1 however 4 influence 3 the 4 influence 4 influence 5 of 4 influence 15 is 5 of 6 iron 6 iron 8 on 8 on 10 health 9 bone 10 health 10 health 11 in 11 in 14 population 12 the 14 population 13 general 14 population 15 is 16 uncertain the aim of this study was to investigate the relationship between serum ferritin levels and bone mineral density ( bmd ) in elderly koreans . 0 ###LEFT-WALL### 2 aim 0 ###LEFT-WALL### 25 . 1 the 2 aim 2 aim 3 of 2 aim 6 was 3 of 5 study 4 this 5 study 6 was 7 to 6 was 8 investigate 7 to 8 investigate 8 investigate 10 relationship 8 investigate 11 between 8 investigate 22 in 9 the 10 relationship 11 between 15 and 12 serum 14 levels 13 ferritin 14 levels 14 levels 15 and 15 and 18 density 15 and 20 bmd 16 bone 18 density 17 mineral 18 density 19 ( 20 bmd 20 bmd 21 ) 22 in 24 koreans 23 elderly 24 koreans a total of 2,943 subjects aged 65 years and over who participated in the 2008 - 2010 korea national health and nutrition examination surveys were included in this study . 0 ###LEFT-WALL### 2 total 0 ###LEFT-WALL### 6 aged 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 30 . 1 a 2 total 2 total 3 of 2 total 6 aged 3 of 5 subjects 4 2,943 5 subjects 6 aged 8 years 7 65 8 years 9 and 24 surveys 9 and 26 included 10 over 11 who 10 over 16 - 10 over 24 surveys 11 who 12 participated 12 participated 13 in 13 in 15 2008 14 the 15 2008 17 2010 18 korea 18 korea 19 national 19 national 20 health 20 health 21 and 21 and 22 nutrition 22 nutrition 23 examination 23 examination 24 surveys 24 surveys 25 were 25 were 26 included 26 included 27 in 27 in 29 study 28 this 29 study age , physical activity , current smoking status , alcohol consumption , education level , household income , and dietary assessment were surveyed by a face [-] to - face interview . 0 ###LEFT-WALL### 19 and 0 ###LEFT-WALL### 29 - 0 ###LEFT-WALL### 32 . 1 age 4 activity 1 age 19 and 2 , 4 activity 3 physical 4 activity 4 activity 8 status 4 activity 17 income 4 activity 18 , 5 , 8 status 6 current 7 smoking 7 smoking 8 status 8 status 11 consumption 8 status 12 , 9 , 11 consumption 10 alcohol 11 consumption 11 consumption 12 , 12 , 17 income 13 education 17 income 14 level 15 , 14 level 16 household 16 household 17 income 17 income 18 , 19 and 20 dietary 19 and 21 assessment 19 and 28 to 21 assessment 22 were 22 were 23 surveyed 23 surveyed 24 by 23 surveyed 28 to 24 by 26 face 25 a 26 face 29 - 31 interview 30 face 31 interview bmd was measured at the lumbar spine and femur by dual - energy x - ray absorptiometry , and other biochemical markers , including serum ferritin , 25 - hydroxyvitamin d3 , serum alkaline phosphatase , and parathyroid hormone , were assayed . 0 ###LEFT-WALL### 1 bmd 0 ###LEFT-WALL### 2 was 0 ###LEFT-WALL### 15 - 0 ###LEFT-WALL### 43 . 1 bmd 2 was 2 was 3 measured 3 measured 4 at 4 at 8 and 5 the 7 spine 6 lumbar 7 spine 7 spine 8 and 8 and 9 femur 8 and 10 by 10 by 13 energy 11 dual 12 - 11 dual 13 energy 13 energy 14 x 15 - 19 and 15 - 42 assayed 16 ray 17 absorptiometry 17 absorptiometry 19 and 18 , 19 and 19 and 22 markers 19 and 24 including 19 and 28 25 19 and 31 d3 19 and 41 were 20 other 22 markers 21 biochemical 22 markers 23 , 24 including 24 including 26 ferritin 24 including 27 , 25 serum 26 ferritin 27 , 28 25 28 25 29 - 29 - 31 d3 30 hydroxyvitamin 31 d3 31 d3 37 and 31 d3 40 , 32 , 37 and 33 serum 35 phosphatase 34 alkaline 35 phosphatase 35 phosphatase 37 and 36 , 37 and 37 and 39 hormone 37 and 40 , 38 parathyroid 39 hormone 41 were 42 assayed after adjusting for age and body mass index , we found an association between bmd of the total lumbar spine , total femur , and femur neck and levels of alkaline phosphatase , parathyroid hormone , vitamin d3 , and daily intake of calcium and protein . 0 ###LEFT-WALL### 10 we 0 ###LEFT-WALL### 11 found 0 ###LEFT-WALL### 47 . 1 after 2 adjusting 1 after 10 we 3 for 5 and 3 for 9 , 3 for 10 we 4 age 5 and 5 and 8 index 6 body 7 mass 7 mass 8 index 10 we 11 found 11 found 45 and 12 an 13 association 13 association 14 between 13 association 28 and 14 between 15 bmd 15 bmd 16 of 16 of 25 and 17 the 20 spine 18 total 20 spine 19 lumbar 20 spine 20 spine 21 , 21 , 23 femur 21 , 25 and 22 total 23 femur 24 , 25 and 25 and 27 neck 26 femur 27 neck 28 and 29 levels 28 and 30 of 28 and 45 and 30 of 40 and 31 alkaline 32 phosphatase 32 phosphatase 33 , 33 , 35 hormone 33 , 36 , 34 parathyroid 35 hormone 36 , 38 d3 36 , 40 and 37 vitamin 38 d3 39 , 40 and 40 and 42 intake 40 and 43 of 41 daily 42 intake 43 of 44 calcium 45 and 46 protein serum ferritin levels were positively associated with bmd of the total lumbar spine , total femur , and femur neck after adjusting for all covariates in men , but not in women . 0 ###LEFT-WALL### 1 serum 0 ###LEFT-WALL### 6 associated 0 ###LEFT-WALL### 33 . 1 serum 3 levels 1 serum 4 were 1 serum 6 associated 2 ferritin 3 levels 3 levels 4 were 4 were 5 positively 6 associated 7 with 6 associated 21 after 6 associated 23 for 7 with 8 bmd 8 bmd 9 of 9 of 18 and 10 the 13 spine 11 total 13 spine 12 lumbar 13 spine 13 spine 14 , 14 , 16 femur 14 , 18 and 15 total 16 femur 17 , 18 and 18 and 20 neck 19 femur 20 neck 21 after 22 adjusting 23 for 25 covariates 24 all 25 covariates 25 covariates 29 but 26 in 27 men 26 in 29 but 28 , 29 but 29 but 30 not 29 but 31 in 31 in 32 women this study suggests a positive association between serum ferritin levels and bmd in elderly south korean men without hematologic disorders . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 suggests 0 ###LEFT-WALL### 21 . 1 this 2 study 2 study 3 suggests 3 suggests 6 association 3 suggests 7 between 3 suggests 13 in 3 suggests 18 without 4 a 5 positive 4 a 6 association 5 positive 6 association 7 between 11 and 8 serum 10 levels 9 ferritin 10 levels 10 levels 11 and 11 and 12 bmd 13 in 17 men 14 elderly 16 korean 15 south 16 korean 16 korean 17 men 18 without 20 disorders 19 hematologic 20 disorders further study is warranted to verify the effects of iron on bone metabolism . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 4 warranted 0 ###LEFT-WALL### 14 . 1 further 2 study 2 study 3 is 3 is 4 warranted 4 warranted 5 to 5 to 6 verify 6 verify 8 effects 6 verify 11 on 7 the 8 effects 8 effects 9 of 9 of 10 iron 11 on 13 metabolism 12 bone 13 metabolism coinfection of hepatitis [b] virus ( hbv ) with hepatitis c virus ( hcv ) is quite common , leading to an increase in morbidity and mortality . 0 ###LEFT-WALL### 12 virus 0 ###LEFT-WALL### 16 is 1 coinfection 12 virus 2 of 5 virus 2 of 12 virus 3 hepatitis 5 virus 5 virus 7 hbv 6 ( 7 hbv 7 hbv 8 ) 9 with 10 hepatitis 9 with 12 virus 10 hepatitis 11 c 12 virus 14 hcv 12 virus 16 is 13 ( 14 hcv 14 hcv 15 ) 16 is 18 common 17 quite 18 common 18 common 20 leading 19 , 20 leading 20 leading 21 to 20 leading 24 in 20 leading 28 . 21 to 23 increase 22 an 23 increase 24 in 26 and 25 morbidity 26 and 26 and 27 mortality as such [,] hbv vaccination is recommended in hcv - infected individuals . 0 ###LEFT-WALL### 5 vaccination 0 ###LEFT-WALL### 7 recommended 0 ###LEFT-WALL### 10 - 1 as 4 hbv 1 as 5 vaccination 2 such 4 hbv 5 vaccination 6 is 6 is 7 recommended 7 recommended 8 in 8 in 9 hcv 10 - 12 individuals 10 - 13 . 11 infected 12 individuals however , hbv vaccine responses in hcv [-] infected individuals are often blunted compared with uninfected populations . 0 ###LEFT-WALL### 5 responses 0 ###LEFT-WALL### 14 compared 0 ###LEFT-WALL### 18 . 1 however 2 , 1 however 5 responses 3 hbv 5 responses 4 vaccine 5 responses 5 responses 6 in 5 responses 13 blunted 5 responses 14 compared 6 in 7 hcv 7 hcv 9 infected 7 hcv 10 individuals 7 hcv 11 are 10 individuals 11 are 11 are 12 often 14 compared 15 with 15 with 17 populations 16 uninfected 17 populations the mechanism for this failure of vaccine response [in] hcv [-] infected subjects remains unclear . 0 ###LEFT-WALL### 2 mechanism 0 ###LEFT-WALL### 14 remains 0 ###LEFT-WALL### 16 . 1 the 2 mechanism 2 mechanism 3 for 2 mechanism 14 remains 3 for 5 failure 4 this 5 failure 5 failure 6 of 6 of 13 subjects 7 vaccine 12 infected 8 response 12 infected 10 hcv 12 infected 12 infected 13 subjects 14 remains 15 unclear in this study , we investigated the expression and function of an inhibitory receptor , killer cell lectin - like receptor subfamily g member 1 ( klrg1 ) , in the regulation of cd4 [(] [+] [ )(t cells and hbv vaccine responses during hcv infection . 0 ###LEFT-WALL### 5 we 0 ###LEFT-WALL### 6 investigated 0 ###LEFT-WALL### 47 . 1 in 3 study 1 in 4 , 1 in 5 we 2 this 3 study 5 we 6 investigated 6 investigated 9 and 6 investigated 30 in 6 investigated 44 during 7 the 9 and 8 expression 9 and 9 and 10 function 9 and 11 of 11 of 14 receptor 12 an 13 inhibitory 12 an 14 receptor 13 inhibitory 14 receptor 14 receptor 18 lectin 15 , 18 lectin 16 killer 17 cell 17 cell 18 lectin 18 lectin 20 like 18 lectin 29 , 19 - 20 like 20 like 24 member 20 like 29 , 21 receptor 24 member 22 subfamily 23 g 22 subfamily 24 member 24 member 25 1 24 member 27 klrg1 26 ( 27 klrg1 27 klrg1 28 ) 30 in 40 and 31 the 32 regulation 32 regulation 33 of 32 regulation 40 and 33 of 39 cells 34 cd4 38 )(t 34 cd4 39 cells 40 and 43 responses 41 hbv 43 responses 42 vaccine 43 responses 44 during 46 infection 45 hcv 46 infection we demonstrated that klrg1 was overexpressed on cd4 ( [+] [ )( cells from hcv - infected , hbv vaccine nonresponders compared with hbv vaccine responders . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 demonstrated 0 ###LEFT-WALL### 18 , 0 ###LEFT-WALL### 27 . 1 we 2 demonstrated 2 demonstrated 3 that 3 that 4 klrg1 3 that 6 overexpressed 4 klrg1 5 was 5 was 6 overexpressed 6 overexpressed 7 on 6 overexpressed 17 infected 7 on 8 cd4 8 cd4 13 cells 9 ( 13 cells 13 cells 14 from 13 cells 16 - 14 from 15 hcv 16 - 17 infected 17 infected 18 , 18 , 21 nonresponders 18 , 22 compared 19 hbv 20 vaccine 20 vaccine 21 nonresponders 21 nonresponders 22 compared 22 compared 23 with 23 with 24 hbv 23 with 26 responders 25 vaccine 26 responders the capacity of cd4 [(] [+] [ )(t cells to proliferate and secrete il - 2 [cytokine] was inversely associated with the level of klrg1 expression . 0 ###LEFT-WALL### 2 capacity 0 ###LEFT-WALL### 20 associated 0 ###LEFT-WALL### 27 . 1 the 2 capacity 2 capacity 3 of 2 capacity 10 to 2 capacity 12 and 2 capacity 18 was 3 of 9 cells 4 cd4 8 )(t 4 cd4 9 cells 10 to 12 and 11 proliferate 12 and 12 and 13 secrete 12 and 16 2 13 secrete 14 il 15 - 16 2 18 was 20 associated 19 inversely 20 associated 20 associated 21 with 21 with 23 level 22 the 23 level 23 level 24 of 24 of 26 expression 25 klrg1 26 expression importantly , blocking klrg1 signaling resulted in a significant improvement in cd4 [(] [+] [ )(t cell proliferation and il - 2 production in hcv - infected , hbv vaccine nonresponders in response to tcr stimulation . 0 ###LEFT-WALL### 5 signaling 0 ###LEFT-WALL### 6 resulted 1 importantly 2 , 1 importantly 5 signaling 3 blocking 5 signaling 4 klrg1 5 signaling 5 signaling 6 resulted 6 resulted 7 in 6 resulted 11 in 7 in 10 improvement 8 a 10 improvement 9 significant 10 improvement 11 in 19 and 12 cd4 16 )(t 12 cd4 17 cell 17 cell 18 proliferation 18 proliferation 19 and 19 and 20 il 19 and 27 infected 19 and 31 nonresponders 20 il 23 production 21 - 23 production 22 2 23 production 23 production 24 in 23 production 26 - 24 in 25 hcv 28 , 31 nonresponders 29 hbv 30 vaccine 30 vaccine 31 nonresponders 31 nonresponders 33 response 31 nonresponders 34 to 31 nonresponders 37 . 32 in 33 response 34 to 36 stimulation 35 tcr 36 stimulation moreover , blockade [of] klrg1 increased the phosphorylation of akt ( ser ( 473 ) ) and decreased the expression of cell cycle inhibitors p16 ( ink4a ) and p27 ( kip1 ) , which subsequently enhanced the expression of cyclin [-] dependent kinase 2 and cyclin e [.] these results suggest that the klrg1 pathway impairs cd4 [(] [+] [ )(t cell responses to neoantigen and [induces] a state of immune senescence in individuals with hcv infection , raising the possibility that blocking this negative - signaling pathway might improve hbv vaccine responses in the setting of chronic viral infection [.] 0 ###LEFT-WALL### 3 blockade 1 moreover 2 , 1 moreover 3 blockade 3 blockade 5 klrg1 5 klrg1 17 and 6 increased 8 phosphorylation 6 increased 17 and 7 the 8 phosphorylation 8 phosphorylation 9 of 9 of 10 akt 10 akt 12 ser 11 ( 12 ser 12 ser 14 473 12 ser 16 ) 13 ( 14 473 14 473 15 ) 17 and 18 decreased 17 and 29 and 19 the 20 expression 20 expression 21 of 20 expression 29 and 21 of 22 cell 22 cell 24 inhibitors 22 cell 25 p16 22 cell 27 ink4a 23 cycle 24 inhibitors 24 inhibitors 25 p16 26 ( 27 ink4a 27 ink4a 28 ) 29 and 30 p27 29 and 32 kip1 29 and 35 which 31 ( 32 kip1 32 kip1 33 ) 34 , 35 which 35 which 37 enhanced 36 subsequently 37 enhanced 37 enhanced 46 and 38 the 39 expression 39 expression 40 of 39 expression 46 and 40 of 44 kinase 41 cyclin 44 kinase 43 dependent 44 kinase 44 kinase 45 2 46 and 47 cyclin 46 and 51 results 46 and 57 impairs 47 cyclin 48 e 50 these 51 results 51 results 52 suggest 52 suggest 53 that 53 that 56 pathway 53 that 57 impairs 54 the 56 pathway 55 klrg1 56 pathway 56 pathway 57 impairs 57 impairs 64 responses 57 impairs 65 to 58 cd4 62 )(t 58 cd4 64 responses 63 cell 64 responses 65 to 67 and 66 neoantigen 67 and 67 and 70 state 67 and 71 of 67 and 76 with 69 a 70 state 71 of 73 senescence 72 immune 73 senescence 73 senescence 74 in 74 in 75 individuals 76 with 78 infection 77 hcv 78 infection 78 infection 80 raising 79 , 80 raising 80 raising 82 possibility 81 the 82 possibility 82 possibility 83 that 83 that 89 pathway 83 that 91 improve 84 blocking 89 pathway 85 this 86 negative 86 negative 87 - 86 negative 89 pathway 88 signaling 89 pathway 89 pathway 90 might 90 might 91 improve 91 improve 94 responses 92 hbv 94 responses 93 vaccine 94 responses 94 responses 95 in 94 responses 98 of 95 in 97 setting 96 the 97 setting 98 of 101 infection 99 chronic 101 infection 100 viral 101 infection to a great extent , cognitive health depends on cerebrovascular health and a deeper understanding of the subtle interactions between cerebrovascular function [and] cognition is needed to protect humans from one of the most devastating affliction , dementia . 0 ###LEFT-WALL### 7 health 0 ###LEFT-WALL### 8 depends 0 ###LEFT-WALL### 12 and 1 to 4 extent 1 to 5 , 1 to 7 health 2 a 3 great 2 a 4 extent 3 great 4 extent 6 cognitive 7 health 7 health 8 depends 8 depends 9 on 9 on 11 health 10 cerebrovascular 11 health 12 and 15 understanding 12 and 26 needed 13 a 15 understanding 14 deeper 15 understanding 15 understanding 16 of 15 understanding 25 is 16 of 19 interactions 17 the 19 interactions 18 subtle 19 interactions 19 interactions 20 between 20 between 24 cognition 21 cerebrovascular 22 function 22 function 24 cognition 25 is 26 needed 26 needed 27 to 26 needed 30 from 27 to 28 protect 28 protect 29 humans 30 from 31 one 31 one 32 of 32 of 36 affliction 33 the 36 affliction 34 most 35 devastating 35 devastating 36 affliction 36 affliction 38 dementia 37 , 38 dementia 38 dementia 39 . however , the underlying biological mechanisms are still not completely clear . 0 ###LEFT-WALL### 6 mechanisms 0 ###LEFT-WALL### 7 are 0 ###LEFT-WALL### 12 . 1 however 2 , 1 however 6 mechanisms 3 the 6 mechanisms 4 underlying 6 mechanisms 5 biological 6 mechanisms 6 mechanisms 7 are 7 are 8 still 7 are 9 not 7 are 11 clear 10 completely 11 clear many studies demonstrated that the neurovascular unit is compromised in cerebrovascular diseases and also in other types of dementia . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 9 compromised 0 ###LEFT-WALL### 20 . 1 many 2 studies 2 studies 3 demonstrated 2 studies 4 that 2 studies 8 is 2 studies 9 compromised 4 that 7 unit 4 that 8 is 5 the 7 unit 6 neurovascular 7 unit 7 unit 8 is 9 compromised 13 and 10 in 12 diseases 10 in 13 and 11 cerebrovascular 12 diseases 13 and 14 also 13 and 15 in 15 in 19 dementia 16 other 17 types 17 types 18 of 17 types 19 dementia 18 of 19 dementia the hemodynamic neurovascular coupling ensures a strong increase of the cerebral blood flow ( cbf ) and an acute increase in neuronal glucose uptake upon increased neural activity . 0 ###LEFT-WALL### 4 coupling 0 ###LEFT-WALL### 5 ensures 0 ###LEFT-WALL### 29 . 1 the 4 coupling 2 hemodynamic 4 coupling 3 neurovascular 4 coupling 4 coupling 5 ensures 5 ensures 17 and 5 ensures 21 in 5 ensures 25 upon 6 a 7 strong 6 a 8 increase 7 strong 8 increase 8 increase 9 of 8 increase 17 and 9 of 13 flow 10 the 13 flow 11 cerebral 12 blood 12 blood 13 flow 13 flow 15 cbf 14 ( 15 cbf 15 cbf 16 ) 17 and 20 increase 18 an 19 acute 18 an 20 increase 19 acute 20 increase 21 in 24 uptake 22 neuronal 23 glucose 23 glucose 24 uptake 25 upon 28 activity 26 increased 28 activity 27 neural 28 activity [dysfunction] of cerebral autoregulation with increasing age along with age - related structural and functional alterations in cerebral blood vessels including accumulation of amyloid - beta ( aβ ) in the media of cortical [arterioles] , neurovascular uncoupling due to astrocyte endfeet retraction [,] impairs the cbf and increases the neuronal degeneration and susceptibility to hypoxia and ischemia . 0 ###LEFT-WALL### 7 age 0 ###LEFT-WALL### 12 related 2 of 4 autoregulation 2 of 7 age 3 cerebral 4 autoregulation 4 autoregulation 5 with 5 with 6 increasing 7 age 9 with 8 along 9 with 9 with 10 age 11 - 12 related 12 related 14 and 13 structural 14 and 14 and 16 alterations 14 and 17 in 14 and 21 including 15 functional 16 alterations 17 in 20 vessels 18 cerebral 19 blood 19 blood 20 vessels 21 including 22 accumulation 22 accumulation 23 of 22 accumulation 30 in 22 accumulation 33 of 23 of 24 amyloid 24 amyloid 26 beta 25 - 26 beta 26 beta 28 aβ 26 beta 29 ) 27 ( 28 aβ 28 aβ 29 ) 30 in 32 media 31 the 32 media 33 of 38 uncoupling 34 cortical 36 , 34 cortical 38 uncoupling 37 neurovascular 38 uncoupling 38 uncoupling 40 to 38 uncoupling 48 and 39 due 40 to 40 to 43 retraction 41 astrocyte 43 retraction 42 endfeet 43 retraction 45 impairs 47 cbf 45 impairs 48 and 46 the 47 cbf 48 and 49 increases 48 and 53 and 50 the 52 degeneration 51 neuronal 52 degeneration 52 degeneration 53 and 53 and 54 susceptibility 53 and 55 to 55 to 57 and 56 hypoxia 57 and 57 and 58 ischemia 57 and 59 . [a] decreased cerebral glucose metabolism is an early event in alzheimer 's disease ( ad ) [pathology] and may precede the neuropathological aβ deposition associated with ad . 0 ###LEFT-WALL### 5 metabolism 0 ###LEFT-WALL### 18 and 0 ###LEFT-WALL### 28 . 2 decreased 4 glucose 3 cerebral 4 glucose 4 glucose 5 metabolism 5 metabolism 18 and 6 is 9 event 6 is 10 in 6 is 18 and 7 an 8 early 7 an 9 event 8 early 9 event 10 in 13 disease 11 alzheimer 12 's 12 's 13 disease 13 disease 15 ad 14 ( 15 ad 15 ad 16 ) 18 and 19 may 19 may 20 precede 20 precede 24 deposition 21 the 24 deposition 22 neuropathological 24 deposition 23 aβ 24 deposition 24 deposition 25 associated 25 associated 26 with 26 with 27 ad aβ accumulation in turn leads to further decreases in the cbf closing the vicious cycle . 0 ###LEFT-WALL### 2 accumulation 0 ###LEFT-WALL### 5 leads 0 ###LEFT-WALL### 16 . 1 aβ 2 accumulation 2 accumulation 5 leads 3 in 4 turn 4 turn 5 leads 5 leads 6 to 6 to 7 further 7 further 8 decreases 7 further 9 in 9 in 11 cbf 10 the 11 cbf 11 cbf 12 closing 12 closing 15 cycle 13 the 15 cycle 14 vicious 15 cycle alzheimer , aging and diabetes are also influenced by insulin/insulin - like growth factor - 1 signaling , and accumulated evidence indicates sporadic ad is associated with disturbed brain insulin metabolism . 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 8 influenced 0 ###LEFT-WALL### 11 - 1 alzheimer 2 , 2 , 3 aging 2 , 4 and 4 and 5 diabetes 4 and 6 are 6 are 8 influenced 7 also 8 influenced 8 influenced 9 by 9 by 10 insulin/insulin 11 - 14 factor 11 - 19 and 11 - 32 . 12 like 13 growth 12 like 14 factor 14 factor 16 1 15 - 16 1 16 1 17 signaling 18 , 19 and 19 and 21 evidence 19 and 22 indicates 20 accumulated 21 evidence 21 evidence 22 indicates 22 indicates 24 ad 22 indicates 26 associated 23 sporadic 24 ad 24 ad 25 is 25 is 26 associated 26 associated 27 with 27 with 31 metabolism 28 disturbed 29 brain 29 brain 31 metabolism 30 insulin 31 metabolism understanding how vascular and metabolic factors interfere with progressive loss of functional neuronal networks becomes essential to develop efficient drugs to prevent cognitive [decline] in [elderly] . 0 ###LEFT-WALL### 1 understanding 0 ###LEFT-WALL### 15 becomes 0 ###LEFT-WALL### 27 . 1 understanding 2 how 1 understanding 15 becomes 2 how 6 factors 2 how 7 interfere 3 vascular 4 and 4 and 5 metabolic 4 and 6 factors 6 factors 7 interfere 7 interfere 8 with 8 with 10 loss 9 progressive 10 loss 10 loss 11 of 11 of 14 networks 12 functional 14 networks 13 neuronal 14 networks 15 becomes 16 essential 16 essential 17 to 16 essential 25 in 17 to 18 develop 18 develop 20 drugs 19 efficient 20 drugs 20 drugs 21 to 20 drugs 22 prevent 20 drugs 23 cognitive 21 to 22 prevent 23 cognitive 25 in we examined experiences and concerns among caregivers of community [-] dwelling people with dementia from two ethnic groups . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 19 . 1 we 4 and 2 examined 3 experiences 2 examined 4 and 4 and 5 concerns 4 and 6 among 4 and 13 with 6 among 7 caregivers 7 caregivers 8 of 8 of 12 people 9 community 12 people 11 dwelling 12 people 13 with 14 dementia 14 dementia 15 from 15 from 18 groups 16 two 18 groups 17 ethnic 18 groups we conducted a thematic analysis of responses to the question , ['] what is your life like as a caregiver ? ['] in nine focus groups ( n = 75 ) with filipino and [non] - hispanic white caregivers . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 conducted 0 ###LEFT-WALL### 11 , 0 ###LEFT-WALL### 21 ? 1 we 2 conducted 2 conducted 5 analysis 3 a 4 thematic 3 a 5 analysis 4 thematic 5 analysis 5 analysis 6 of 6 of 7 responses 7 responses 8 to 8 to 10 question 9 the 10 question 11 , 13 what 11 , 14 is 13 what 14 is 14 is 16 life 15 your 16 life 16 life 17 like 17 like 18 as 18 as 20 caregiver 19 a 20 caregiver 21 ? 25 focus 21 ? 26 groups 21 ? 34 and 21 ? 40 . 23 in 24 nine 23 in 25 focus 25 focus 26 groups 26 groups 29 = 26 groups 32 with 27 ( 29 = 28 n 29 = 29 = 30 75 29 = 31 ) 32 with 33 filipino 34 and 36 - 34 and 38 white 34 and 39 caregivers 37 hispanic 38 white 38 white 39 caregivers constant comparison methods identified themes by ethnicity . 0 ###LEFT-WALL### 3 methods 0 ###LEFT-WALL### 4 identified 0 ###LEFT-WALL### 8 . 1 constant 2 comparison 2 comparison 3 methods 3 methods 4 identified 4 identified 5 themes 4 identified 6 by 6 by 7 ethnicity experiences and concerns expressed across groups were related to care recipient symptoms commonly associated with dementia , including severe memory loss and behavioral changes . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 8 related 0 ###LEFT-WALL### 25 . 1 experiences 2 and 2 and 3 concerns 2 and 4 expressed 2 and 5 across 2 and 7 were 5 across 6 groups 7 were 8 related 8 related 9 to 8 related 15 with 9 to 12 symptoms 10 care 12 symptoms 11 recipient 12 symptoms 12 symptoms 14 associated 13 commonly 14 associated 15 with 22 and 16 dementia 17 , 16 dementia 21 loss 18 including 21 loss 19 severe 20 memory 20 memory 21 loss 21 loss 22 and 22 and 24 changes 23 behavioral 24 changes participants in both ethnic groups described strategies that help them cope , such as receiving help from family and friends , receiving respite support , and participating in support groups . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 6 described 0 ###LEFT-WALL### 26 and 0 ###LEFT-WALL### 31 . 1 participants 2 in 1 participants 6 described 2 in 5 groups 3 both 5 groups 4 ethnic 5 groups 6 described 7 strategies 7 strategies 8 that 7 strategies 9 help 7 strategies 22 receiving 8 that 9 help 9 help 10 them 9 help 11 cope 11 cope 14 as 12 , 14 as 13 such 14 as 14 as 16 help 14 as 21 , 15 receiving 16 help 16 help 17 from 17 from 19 and 18 family 19 and 19 and 20 friends 21 , 22 receiving 22 receiving 24 support 22 receiving 25 , 23 respite 24 support 26 and 27 participating 26 and 30 groups 27 participating 28 in 27 participating 30 groups 28 in 29 support filipino caregivers more often emphasized positive aspects of caregiving , whereas whites often expressed that others do not understand the daily experiences of caregiving . 0 ###LEFT-WALL### 2 caregivers 0 ###LEFT-WALL### 5 emphasized 0 ###LEFT-WALL### 10 , 0 ###LEFT-WALL### 25 . 1 filipino 2 caregivers 2 caregivers 5 emphasized 3 more 4 often 4 often 5 emphasized 5 emphasized 7 aspects 6 positive 7 aspects 7 aspects 8 of 8 of 9 caregiving 10 , 16 others 10 , 19 understand 11 whereas 12 whites 11 whereas 14 expressed 11 whereas 16 others 12 whites 14 expressed 13 often 14 expressed 14 expressed 15 that 16 others 17 do 17 do 18 not 17 do 19 understand 19 understand 22 experiences 20 the 22 experiences 21 daily 22 experiences 22 experiences 23 of 23 of 24 caregiving filipinos more commonly described caregivers as a ['] good person ['] or ['] saint ['] and emphasized that caregiving made them stronger . 0 ###LEFT-WALL### 1 filipinos 0 ###LEFT-WALL### 16 and 0 ###LEFT-WALL### 23 . 1 filipinos 2 more 1 filipinos 4 described 1 filipinos 16 and 2 more 4 described 3 commonly 4 described 5 caregivers 6 as 5 caregivers 16 and 6 as 12 or 7 a 10 person 9 good 10 person 10 person 12 or 12 or 14 saint 16 and 17 emphasized 17 emphasized 18 that 18 that 19 caregiving 18 that 20 made 19 caregiving 20 made 20 made 21 them 20 made 22 stronger this paper offers a critique of dementia care mapping ( dcm ) as a practice development and research tool by examining the psychometric properties and efficacy of dcm as a method for evaluating and enhancing care quality and quality of life . 0 ###LEFT-WALL### 2 paper 0 ###LEFT-WALL### 42 . 1 this 2 paper 2 paper 3 offers 3 offers 5 critique 3 offers 9 mapping 3 offers 13 as 4 a 5 critique 5 critique 6 of 6 of 8 care 7 dementia 8 care 9 mapping 11 dcm 10 ( 11 dcm 11 dcm 12 ) 13 as 25 and 14 a 15 practice 14 a 16 development 15 practice 16 development 16 development 17 and 17 and 19 tool 17 and 20 by 17 and 25 and 18 research 19 tool 20 by 21 examining 21 examining 24 properties 22 the 24 properties 23 psychometric 24 properties 25 and 26 efficacy 25 and 27 of 27 of 28 dcm 28 dcm 29 as 29 as 38 and 30 a 31 method 31 method 32 for 31 method 34 and 32 for 33 evaluating 34 and 37 quality 34 and 38 and 35 enhancing 37 quality 36 care 37 quality 38 and 39 quality 38 and 40 of 40 of 41 life based on a review and analysis of the published empirical studies utilizing dcm , it becomes apparent that there is mixed support for the tool 's validity and reliability . 0 ###LEFT-WALL### 15 it 0 ###LEFT-WALL### 30 . 1 based 2 on 1 based 14 , 1 based 15 it 2 on 5 and 3 a 4 review 4 review 5 and 5 and 6 analysis 5 and 14 , 6 analysis 7 of 6 analysis 12 utilizing 7 of 11 studies 8 the 11 studies 9 published 11 studies 10 empirical 11 studies 12 utilizing 13 dcm 15 it 16 becomes 16 becomes 17 apparent 17 apparent 18 that 18 that 19 there 18 that 20 is 19 there 20 is 20 is 22 support 21 mixed 22 support 22 support 23 for 23 for 28 and 24 the 25 tool 25 tool 26 's 26 's 27 validity 27 validity 28 and 28 and 29 reliability more importantly , there is a need for additional studies specifically examining the range of related assessments to provide conclusive evidence for dcm 's relevance [,] applicability and reliability as a practice and research tool in dementia care . 0 ###LEFT-WALL### 4 there 0 ###LEFT-WALL### 24 's 0 ###LEFT-WALL### 39 . 1 more 2 importantly 2 importantly 3 , 2 importantly 4 there 4 there 5 is 5 is 7 need 6 a 7 need 7 need 8 for 8 for 10 studies 9 additional 10 studies 10 studies 12 examining 11 specifically 12 examining 12 examining 14 range 12 examining 24 's 13 the 14 range 14 range 15 of 14 range 18 to 14 range 19 provide 14 range 24 's 15 of 17 assessments 16 related 17 assessments 18 to 19 provide 19 provide 21 evidence 19 provide 22 for 20 conclusive 21 evidence 22 for 23 dcm 24 's 28 and 24 's 30 as 24 's 36 in 25 relevance 27 applicability 27 applicability 28 and 28 and 29 reliability 30 as 35 tool 31 a 35 tool 32 practice 33 and 33 and 34 research 33 and 35 tool 36 in 38 care 37 dementia 38 care the paper identifies methodological issues of implementation and use of dcm , i.e [.] , coding practices , mapping duration . 0 ###LEFT-WALL### 2 paper 0 ###LEFT-WALL### 3 identifies 0 ###LEFT-WALL### 21 . 1 the 2 paper 2 paper 3 identifies 3 identifies 8 and 4 methodological 5 issues 5 issues 6 of 5 issues 8 and 6 of 7 implementation 8 and 9 use 8 and 10 of 8 and 19 mapping 10 of 11 dcm 11 dcm 17 practices 12 , 17 practices 13 i.e 15 , 13 i.e 17 practices 16 coding 17 practices 17 practices 18 , 19 mapping 20 duration also , a summary of the tool 's strengths and limitations in practice and research settings , areas for improvement and future research avenues is provided . 0 ###LEFT-WALL### 4 summary 0 ###LEFT-WALL### 25 is 0 ###LEFT-WALL### 27 . 1 also 2 , 1 also 4 summary 3 a 4 summary 4 summary 5 of 4 summary 12 in 4 summary 25 is 5 of 10 and 6 the 7 tool 7 tool 8 's 8 's 9 strengths 9 strengths 10 and 10 and 11 limitations 12 in 21 and 13 practice 14 and 14 and 16 settings 14 and 17 , 15 research 16 settings 17 , 18 areas 17 , 21 and 18 areas 19 for 19 for 20 improvement 21 and 24 avenues 22 future 23 research 23 research 24 avenues 25 is 26 provided urban centers are increasingly ethnically diverse . 0 ###LEFT-WALL### 2 centers 0 ###LEFT-WALL### 3 are 0 ###LEFT-WALL### 7 . 1 urban 2 centers 2 centers 3 are 3 are 4 increasingly 3 are 6 diverse 5 ethnically 6 diverse however , some visible minorities are less likely than their majority counterparts to seek [and] receive services and treatment for dementia . 0 ###LEFT-WALL### 3 some 0 ###LEFT-WALL### 16 receive 0 ###LEFT-WALL### 22 . 1 however 2 , 1 however 3 some 3 some 5 minorities 3 some 14 seek 3 some 16 receive 4 visible 5 minorities 5 minorities 6 are 6 are 8 likely 7 less 8 likely 8 likely 9 than 8 likely 13 to 8 likely 14 seek 9 than 12 counterparts 10 their 12 counterparts 11 majority 12 counterparts 13 to 14 seek 16 receive 18 and 17 services 18 and 18 and 19 treatment 18 and 20 for 20 for 21 dementia this study explored experiences of south asian canadians , canada 's largest visible minority group , prior to dementia diagnosis . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 explored 0 ###LEFT-WALL### 21 . 1 this 2 study 2 study 3 explored 3 explored 4 experiences 3 explored 18 to 4 experiences 5 of 5 of 8 canadians 6 south 8 canadians 7 asian 8 canadians 8 canadians 15 group 9 , 15 group 10 canada 11 's 11 's 12 largest 11 's 15 group 13 visible 14 minority 14 minority 15 group 15 group 16 , 17 prior 18 to 18 to 20 diagnosis 19 dementia 20 diagnosis six persons with dementia [and] eight of their family carers described their early perceptions of dementia - related changes , actions taken , including help seeking and diagnosis , and affective responses . 0 ###LEFT-WALL### 2 persons 0 ###LEFT-WALL### 11 described 0 ###LEFT-WALL### 33 . 1 six 2 persons 2 persons 3 with 2 persons 7 of 2 persons 11 described 3 with 4 dementia 4 dementia 6 eight 7 of 10 carers 8 their 10 carers 9 family 10 carers 11 described 30 and 12 their 14 perceptions 13 early 14 perceptions 14 perceptions 15 of 14 perceptions 24 including 14 perceptions 27 and 15 of 16 dementia 17 - 18 related 18 related 19 changes 18 related 23 , 18 related 24 including 19 changes 21 actions 20 , 21 actions 21 actions 22 taken 21 actions 23 , 24 including 26 seeking 25 help 26 seeking 27 and 28 diagnosis 27 and 30 and 29 , 30 and 30 and 32 responses 31 affective 32 responses early signs were attributed to aging [or] personality . 0 ###LEFT-WALL### 2 signs 0 ###LEFT-WALL### 4 attributed 0 ###LEFT-WALL### 9 . 1 early 2 signs 2 signs 3 were 3 were 4 attributed 4 attributed 5 to 5 to 6 aging 6 aging 8 personality even after cognitive enhancers were prescribed , some respondents continued to believe that the dementia symptoms were ['] normal ['] . 0 ###LEFT-WALL### 9 respondents 0 ###LEFT-WALL### 10 continued 0 ###LEFT-WALL### 21 . 1 even 2 after 1 even 7 , 1 even 9 respondents 2 after 4 enhancers 2 after 6 prescribed 3 cognitive 4 enhancers 4 enhancers 5 were 5 were 6 prescribed 6 prescribed 7 , 8 some 9 respondents 9 respondents 10 continued 10 continued 11 to 11 to 12 believe 12 believe 13 that 13 that 16 symptoms 13 that 17 were 14 the 16 symptoms 15 dementia 16 symptoms 16 symptoms 17 were 17 were 19 normal family carers ' affective responses may be related to their attributions . 0 ###LEFT-WALL### 5 responses 0 ###LEFT-WALL### 8 related 0 ###LEFT-WALL### 12 . 1 family 2 carers 2 carers 3 ' 3 ' 5 responses 4 affective 5 responses 5 responses 6 may 6 may 7 be 7 be 8 related 8 related 9 to 9 to 11 attributions 10 their 11 attributions before seeking medical attention , family carers modified physical or social environments because of symptoms . 0 ###LEFT-WALL### 7 carers 0 ###LEFT-WALL### 8 modified 0 ###LEFT-WALL### 16 . 1 before 2 seeking 1 before 5 , 1 before 7 carers 2 seeking 4 attention 3 medical 4 attention 6 family 7 carers 7 carers 8 modified 8 modified 12 environments 8 modified 13 because 9 physical 10 or 10 or 11 social 10 or 12 environments 13 because 14 of 14 of 15 symptoms help seeking was delayed up to four years , even with significant dementia symptoms . 0 ###LEFT-WALL### 2 seeking 0 ###LEFT-WALL### 9 , 0 ###LEFT-WALL### 15 . 1 help 2 seeking 2 seeking 3 was 3 was 9 , 4 delayed 8 years 4 delayed 9 , 5 up 6 to 6 to 7 four 7 four 8 years 9 , 10 even 9 , 11 with 11 with 14 symptoms 12 significant 14 symptoms 13 dementia 14 symptoms recognition of a health problem was influenced by safety concerns , emergence [of] new symptoms following trauma , and treatment for other health problems . 0 ###LEFT-WALL### 1 recognition 0 ###LEFT-WALL### 7 influenced 0 ###LEFT-WALL### 25 . 1 recognition 2 of 1 recognition 6 was 2 of 5 problem 3 a 4 health 3 a 5 problem 4 health 5 problem 6 was 7 influenced 7 influenced 8 by 7 influenced 21 for 8 by 19 and 9 safety 10 concerns 10 concerns 11 , 11 , 17 trauma 11 , 19 and 12 emergence 17 trauma 14 new 15 symptoms 15 symptoms 16 following 16 following 17 trauma 18 , 19 and 19 and 20 treatment 21 for 24 problems 22 other 24 problems 23 health 24 problems for some , relatives living outside the home or outside canada were instrumental in recognizing a problem and convincing family carers and persons with dementia to seek medical attention . 0 ###LEFT-WALL### 1 for 0 ###LEFT-WALL### 12 were 0 ###LEFT-WALL### 30 . 1 for 9 or 1 for 12 were 2 some 3 , 3 , 4 relatives 3 , 9 or 4 relatives 5 living 4 relatives 6 outside 6 outside 8 home 7 the 8 home 9 or 10 outside 11 canada 12 were 12 were 13 instrumental 13 instrumental 14 in 13 instrumental 26 to 14 in 15 recognizing 15 recognizing 22 and 15 recognizing 24 with 16 a 17 problem 17 problem 18 and 18 and 21 carers 18 and 22 and 19 convincing 21 carers 20 family 21 carers 22 and 23 persons 24 with 25 dementia 26 to 27 seek 27 seek 29 attention 28 medical 29 attention the pathway to diagnosis might be easier with outreach to help south asian immigrants differentiate between normal aging and dementia . 0 ###LEFT-WALL### 2 pathway 0 ###LEFT-WALL### 6 be 0 ###LEFT-WALL### 21 . 1 the 2 pathway 2 pathway 3 to 2 pathway 5 might 3 to 4 diagnosis 5 might 6 be 6 be 7 easier 7 easier 8 with 7 easier 10 to 7 easier 15 differentiate 8 with 9 outreach 10 to 11 help 11 help 14 immigrants 11 help 15 differentiate 12 south 14 immigrants 13 asian 14 immigrants 15 differentiate 16 between 16 between 19 and 17 normal 18 aging 17 normal 19 and 19 and 20 dementia symptom recognition by physicians treating other acute conditions was a portal to dementia services for others . 0 ###LEFT-WALL### 2 recognition 0 ###LEFT-WALL### 9 was 0 ###LEFT-WALL### 17 . 1 symptom 2 recognition 2 recognition 3 by 2 recognition 9 was 3 by 4 physicians 4 physicians 5 treating 5 treating 8 conditions 6 other 8 conditions 7 acute 8 conditions 9 was 11 portal 10 a 11 portal 11 portal 12 to 12 to 14 services 13 dementia 14 services 14 services 15 for 15 for 16 others screening [and] referral in acute care could result in earlier diagnosis and treatment . 0 ###LEFT-WALL### 3 referral 0 ###LEFT-WALL### 8 result 0 ###LEFT-WALL### 14 . 1 screening 3 referral 3 referral 4 in 3 referral 7 could 4 in 6 care 5 acute 6 care 7 could 8 result 8 result 9 in 9 in 12 and 10 earlier 11 diagnosis 11 diagnosis 12 and 12 and 13 treatment background : optical coherence tomography [(] oct [ )(of the anterior segment allows quantitative analysis of the geometry of the chamber angle . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 23 . 1 background 2 : 2 : 5 tomography 3 optical 4 coherence 4 coherence 5 tomography 5 tomography 7 oct 5 tomography 13 allows 7 oct 9 )(of 7 oct 13 allows 9 )(of 12 segment 10 the 12 segment 11 anterior 12 segment 13 allows 15 analysis 14 quantitative 15 analysis 15 analysis 16 of 15 analysis 19 of 16 of 18 geometry 17 the 18 geometry 19 of 22 angle 20 the 22 angle 21 chamber 22 angle we performed bilateral spectral - domain oct measurements in healthy , emmetropic , hyperopic , and myopic subjects to establish correlations between the width of the angle , the refraction , and intraocular pressure of the test persons . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 performed 0 ###LEFT-WALL### 39 . 1 we 2 performed 2 performed 8 measurements 2 performed 19 to 3 bilateral 6 domain 4 spectral 5 - 4 spectral 6 domain 6 domain 8 measurements 7 oct 8 measurements 8 measurements 9 in 9 in 18 subjects 10 healthy 11 , 10 healthy 18 subjects 12 emmetropic 13 , 12 emmetropic 18 subjects 14 hyperopic 16 and 15 , 16 and 16 and 17 myopic 16 and 18 subjects 19 to 20 establish 20 establish 21 correlations 20 establish 22 between 22 between 32 and 23 the 24 width 24 width 25 of 24 width 32 and 25 of 27 angle 26 the 27 angle 27 angle 30 refraction 28 , 30 refraction 29 the 30 refraction 30 refraction 31 , 31 , 32 and 32 and 34 pressure 32 and 35 of 33 intraocular 34 pressure 35 of 38 persons 36 the 38 persons 37 test 38 persons methods : out of 4,617 eyes ( 2,309 subjects ) , those with refractive errors of < [-] 4 or [>] +3 diopters were identified by objective refraction measurement ( kr - 8800 kerato - refractometer , topcon inc . , japan ) and examined using the anterior segment mode of a spectral - domain 3 d oct - 2000 ( topcon inc . , japan ) . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 11 , 1 methods 2 : 2 : 3 out 3 out 4 of 4 of 6 eyes 5 4,617 6 eyes 6 eyes 9 subjects 7 ( 9 subjects 8 2,309 9 subjects 9 subjects 10 ) 11 , 20 or 12 those 13 with 12 those 20 or 13 with 15 errors 14 refractive 15 errors 15 errors 16 of 16 of 19 4 17 < 19 4 20 or 22 +3 20 or 23 diopters 20 or 24 were 20 or 25 identified 23 diopters 24 were 25 identified 26 by 26 by 29 measurement 27 objective 28 refraction 28 refraction 29 measurement 29 measurement 31 kr 29 measurement 35 - 30 ( 31 kr 31 kr 32 - 32 - 35 - 33 8800 34 kerato 34 kerato 35 - 35 - 44 and 36 refractometer 39 inc 36 refractometer 44 and 37 , 39 inc 38 topcon 39 inc 39 inc 40 . 39 inc 42 japan 39 inc 43 ) 41 , 42 japan 42 japan 43 ) 44 and 46 using 44 and 48 anterior 44 and 49 segment 45 examined 46 using 47 the 48 anterior 48 anterior 49 segment 49 segment 50 mode 50 mode 51 of 51 of 58 oct 52 a 58 oct 53 spectral 54 - 53 spectral 55 domain 55 domain 58 oct 56 3 57 d 57 d 58 oct 58 oct 60 2000 59 - 60 2000 60 2000 63 inc 60 2000 68 . 61 ( 63 inc 62 topcon 63 inc 63 inc 64 . 63 inc 66 japan 63 inc 68 . 65 , 66 japan 66 japan 67 ) [non] - contact tonometry was performed ( ct - 80 , topcon inc . , japan ) . 0 ###LEFT-WALL### 2 - 0 ###LEFT-WALL### 6 performed 0 ###LEFT-WALL### 18 . 2 - 4 tonometry 3 contact 4 tonometry 4 tonometry 5 was 5 was 6 performed 6 performed 9 - 7 ( 9 - 8 ct 9 - 9 - 10 80 9 - 17 ) 10 80 13 inc 10 80 16 japan 11 , 13 inc 12 topcon 13 inc 13 inc 14 . 13 inc 15 , 15 , 16 japan 16 japan 17 ) one hundred and eight eyes of 54 emmetropic subjects ( [±] 0.5 d [pt] ) served as reference group . 0 ###LEFT-WALL### 5 eyes 0 ###LEFT-WALL### 19 group 0 ###LEFT-WALL### 20 . 1 one 2 hundred 2 hundred 3 and 3 and 4 eight 4 eight 5 eyes 5 eyes 6 of 5 eyes 16 served 5 eyes 19 group 6 of 9 subjects 7 54 9 subjects 8 emmetropic 9 subjects 9 subjects 13 d 10 ( 13 d 12 0.5 13 d 13 d 15 ) 16 served 17 as 17 as 18 reference previous ocular surgery was exclusion [criterion] in all groups . 0 ###LEFT-WALL### 3 surgery 0 ###LEFT-WALL### 4 was 0 ###LEFT-WALL### 10 . 1 previous 3 surgery 2 ocular 3 surgery 3 surgery 4 was 4 was 5 exclusion 5 exclusion 7 in 7 in 9 groups 8 all 9 groups width of the chamber angle was determined using semi - automated software tools and statistical analysis of the data ( pearson correlation , anova with post - [hoc] test and bonferroni correction , regression analysis ) was performed using spss software ( spss 19.0 , chicago , il , usa ) . 0 ###LEFT-WALL### 1 width 0 ###LEFT-WALL### 7 determined 1 width 2 of 1 width 7 determined 2 of 4 chamber 3 the 4 chamber 4 chamber 5 angle 4 chamber 6 was 5 angle 6 was 7 determined 8 using 8 using 16 analysis 9 semi 10 - 9 semi 12 software 11 automated 12 software 12 software 16 analysis 13 tools 14 and 14 and 15 statistical 14 and 16 analysis 16 analysis 17 of 17 of 19 data 18 the 19 data 19 data 22 correlation 19 data 27 - 20 ( 22 correlation 21 pearson 22 correlation 22 correlation 23 , 23 , 27 - 24 anova 25 with 24 anova 27 - 25 with 26 post 27 - 30 and 29 test 30 and 30 and 31 bonferroni 30 and 32 correction 30 and 37 was 30 and 38 performed 32 correction 35 analysis 32 correction 37 was 33 , 35 analysis 34 regression 35 analysis 35 analysis 36 ) 38 performed 39 using 39 using 41 software 40 spss 41 software 41 software 43 spss 41 software 48 il 42 ( 43 spss 43 spss 44 19.0 43 spss 45 , 45 , 48 il 46 chicago 48 il 47 , 48 il 48 il 49 , 48 il 50 usa 48 il 52 . 49 , 50 usa 50 usa 51 ) results : six hundred and sixty - eight eyes [of] 398 persons ( 292 male [,] 96 [female] ) were [included] in the study . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 7 - 1 results 2 : 2 : 6 sixty 3 six 4 hundred 4 hundred 5 and 5 and 6 sixty 7 - 12 persons 7 - 20 were 7 - 25 . 8 eight 12 persons 9 eyes 12 persons 11 398 12 persons 12 persons 15 male 12 persons 20 were 13 ( 15 male 14 292 15 male 15 male 17 96 15 male 19 ) 20 were 22 in 22 in 24 study 23 the 24 study mean hyperopic refraction was +4.24 ( +3 to +7.75 ) [dpt] , mean myopic refraction was - 5.86 ( - 4 to - 11.75 ) [dpt] . 0 ###LEFT-WALL### 12 , 0 ###LEFT-WALL### 27 . 1 mean 3 refraction 1 mean 4 was 1 mean 12 , 2 hyperopic 3 refraction 3 refraction 4 was 4 was 5 +4.24 5 +4.24 7 +3 6 ( 7 +3 7 +3 8 to 7 +3 10 ) 8 to 9 +7.75 12 , 13 mean 13 mean 15 refraction 13 mean 16 was 14 myopic 15 refraction 15 refraction 16 was 16 was 18 5.86 17 - 18 5.86 18 5.86 22 to 19 ( 22 to 20 - 21 4 21 4 22 to 22 to 24 11.75 22 to 25 ) 23 - 24 11.75 valid chamber angle oct measurements could be obtained from 50 ( 69.4 % ) hyperopic and 400 ( 71.4 % ) [myopic] eyes [meeting] the inclusion criteria . 0 ###LEFT-WALL### 5 measurements 0 ###LEFT-WALL### 8 obtained 0 ###LEFT-WALL### 16 and 0 ###LEFT-WALL### 28 . 1 valid 2 chamber 2 chamber 5 measurements 3 angle 5 measurements 4 oct 5 measurements 5 measurements 6 could 6 could 7 be 7 be 8 obtained 8 obtained 9 from 8 obtained 15 hyperopic 9 from 10 50 10 50 13 % 11 ( 13 % 12 69.4 13 % 13 % 14 ) 16 and 17 400 16 and 23 eyes 17 400 20 % 17 400 23 eyes 18 ( 20 % 19 71.4 20 % 20 % 21 ) 23 eyes 27 criteria 25 the 27 criteria 26 inclusion 27 criteria the mean width of the chamber angle was determined as 31.8 ° [(] range : 13.5 to 45.6 , sd [7.49] ) in the hyperopic group [,] 40.8 ° [(] range [:] 19.3 to 66.0 , sd [8.1] ) in the myopic group , and 36.3 ° [(] range [:] 21.1 to 51.8 , [sd] 6.8 [ )(in the emmetropic reference group . 0 ###LEFT-WALL### 3 width 0 ###LEFT-WALL### 8 was 1 the 3 width 2 mean 3 width 3 width 4 of 3 width 8 was 4 of 7 angle 5 the 7 angle 6 chamber 7 angle 8 was 9 determined 9 determined 10 as 9 determined 15 : 10 as 14 range 11 31.8 12 ° 12 ° 14 range 15 : 16 13.5 15 : 26 group 16 13.5 17 to 16 13.5 23 in 16 13.5 26 group 17 to 18 45.6 18 45.6 20 sd 19 , 20 sd 20 sd 22 ) 23 in 25 hyperopic 24 the 25 hyperopic 26 group 31 range 28 40.8 29 ° 29 ° 31 range 31 range 33 19.3 31 range 34 to 31 range 40 in 34 to 35 66.0 35 66.0 37 sd 36 , 37 sd 37 sd 39 ) 40 in 45 and 41 the 43 group 42 myopic 43 group 43 group 45 and 44 , 45 and 45 and 49 range 46 36.3 47 ° 47 ° 49 range 49 range 51 21.1 49 range 52 to 52 to 53 51.8 53 51.8 56 6.8 54 , 56 6.8 56 6.8 58 )(in 56 6.8 63 . 58 )(in 62 group 59 the 62 group 60 emmetropic 62 group 61 reference 62 group correlation was highly significant ( p > 0.001 ) between refractive error and the aperture of the chamber angle as measured from oct . 0 ###LEFT-WALL### 1 correlation 0 ###LEFT-WALL### 2 was 0 ###LEFT-WALL### 24 . 1 correlation 2 was 2 was 3 highly 2 was 4 significant 4 significant 7 > 4 significant 10 between 5 ( 7 > 6 p 7 > 7 > 8 0.001 7 > 9 ) 10 between 13 and 11 refractive 12 error 12 error 13 and 13 and 15 aperture 13 and 16 of 14 the 15 aperture 16 of 19 angle 17 the 19 angle 18 chamber 19 angle 19 angle 21 measured 20 as 21 measured 21 measured 22 from 22 from 23 oct the association of the intraocular pressure and the refraction was also highly significant ( p > 0.001 ) for the three groups . 0 ###LEFT-WALL### 2 association 0 ###LEFT-WALL### 10 was 0 ###LEFT-WALL### 23 . 1 the 2 association 2 association 3 of 2 association 10 was 3 of 7 and 4 the 6 pressure 5 intraocular 6 pressure 6 pressure 7 and 7 and 9 refraction 8 the 9 refraction 10 was 11 also 10 was 13 significant 12 highly 13 significant 13 significant 16 > 13 significant 19 for 14 ( 16 > 15 p 16 > 16 > 17 0.001 16 > 18 ) 19 for 22 groups 20 the 21 three 21 three 22 groups conclusion : the spectral - domain oct yielded measurements that could be used for digital analysis of the chamber angle geometry . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 22 . 2 : 9 measurements 2 : 20 angle 3 the 9 measurements 4 spectral 5 - 4 spectral 9 measurements 6 domain 8 yielded 7 oct 8 yielded 8 yielded 9 measurements 9 measurements 10 that 9 measurements 11 could 9 measurements 20 angle 10 that 11 could 11 could 12 be 12 be 13 used 13 used 14 for 14 for 16 analysis 15 digital 16 analysis 16 analysis 17 of 17 of 19 chamber 18 the 19 chamber 20 angle 21 geometry our results highlight the correlation between refraction and aperture of the angle in hyperopia and myopia as determined by the 3 d oct - 2000 : hyperopia is associated with a narrower chamber angle , myopia with a wider aperture of the angle . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 highlight 0 ###LEFT-WALL### 18 determined 0 ###LEFT-WALL### 24 - 1 our 2 results 2 results 3 highlight 3 highlight 5 correlation 3 highlight 6 between 3 highlight 13 in 3 highlight 17 as 4 the 5 correlation 6 between 8 and 7 refraction 8 and 8 and 9 aperture 8 and 10 of 10 of 12 angle 11 the 12 angle 13 in 15 and 14 hyperopia 15 and 15 and 16 myopia 17 as 18 determined 18 determined 19 by 19 by 23 oct 20 the 23 oct 21 3 22 d 22 d 23 oct 24 - 25 2000 24 - 26 : 25 2000 26 : 26 : 27 hyperopia 27 hyperopia 28 is 28 is 29 associated 29 associated 30 with 30 with 34 angle 31 a 34 angle 32 narrower 33 chamber 33 chamber 34 angle 34 angle 36 myopia 35 , 36 myopia 36 myopia 37 with 36 myopia 41 of 36 myopia 44 . 37 with 40 aperture 38 a 40 aperture 39 wider 40 aperture 41 of 43 angle 42 the 43 angle the aim of this study was to investigate the influence of the weight - status ( obese , overweight and normal - weight ) on bone mineral density of the forearm in lebanese women . 0 ###LEFT-WALL### 2 aim 0 ###LEFT-WALL### 35 . 1 the 2 aim 2 aim 3 of 2 aim 6 was 3 of 5 study 4 this 5 study 6 was 7 to 6 was 8 investigate 7 to 8 investigate 8 investigate 10 influence 9 the 10 influence 10 influence 11 of 10 influence 25 on 11 of 13 weight 12 the 13 weight 13 weight 15 status 13 weight 23 weight 14 - 15 status 15 status 20 and 15 status 22 - 16 ( 20 and 17 obese 18 , 18 , 19 overweight 18 , 20 and 20 and 21 normal 20 and 22 - 22 - 23 weight 23 weight 24 ) 25 on 28 density 26 bone 28 density 27 mineral 28 density 28 density 29 of 29 of 31 forearm 30 the 31 forearm 31 forearm 32 in 32 in 34 women 33 lebanese 34 women weight and height were measured , and body mass index ( bmi ) [was] calculated . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 4 were 0 ###LEFT-WALL### 16 . 1 weight 2 and 2 and 3 height 2 and 4 were 4 were 15 calculated 5 measured 7 and 6 , 7 and 7 and 10 index 7 and 12 bmi 7 and 15 calculated 8 body 10 index 9 mass 10 index 11 ( 12 bmi 12 bmi 13 ) bmd of the ultra - distal ( ud ) radius , the 1/3 radius and the total radius was measured by dxa ( ge healthcare lunar prodigy ) . 0 ###LEFT-WALL### 1 bmd 0 ###LEFT-WALL### 19 was 0 ###LEFT-WALL### 29 . 1 bmd 2 of 1 bmd 19 was 2 of 15 and 3 the 10 radius 4 ultra 5 - 4 ultra 10 radius 6 distal 8 ud 6 distal 10 radius 7 ( 8 ud 8 ud 9 ) 10 radius 11 , 11 , 14 radius 11 , 15 and 12 the 13 1/3 13 1/3 14 radius 15 and 18 radius 16 the 18 radius 17 total 18 radius 19 was 20 measured 20 measured 21 by 21 by 22 dxa 22 dxa 27 prodigy 23 ( 27 prodigy 24 ge 25 healthcare 25 healthcare 26 lunar 26 lunar 27 prodigy 27 prodigy 28 ) in the whole population , body weight was positively correlated to ud radius bmd ( r = 0.41 [;] p < 0.001 [ )( 1/3 radius bmd ( r = 0.35 [;] p < 0.001 ) [and] total radius bmd ( r = 0.48 [;] p < 0.001 ) while age was negatively correlated to ud bmd ( r = - 0.42 [;] p < 0.001 [ )(, 1/3 radius bmd ( r = - 0.52 [;] p < 0.001 [ )( total radius bmd ( r = - 0.42 [;] p < 0.001 ) . 0 ###LEFT-WALL### 6 body 0 ###LEFT-WALL### 10 correlated 1 in 4 population 1 in 5 , 1 in 6 body 2 the 4 population 3 whole 4 population 6 body 7 weight 6 body 8 was 6 body 10 correlated 7 weight 8 was 9 positively 10 correlated 10 correlated 11 to 10 correlated 21 < 11 to 14 bmd 12 ud 13 radius 13 radius 14 bmd 14 bmd 17 = 15 ( 17 = 16 r 17 = 17 = 18 0.41 20 p 21 < 21 < 26 radius 22 0.001 25 1/3 25 1/3 26 radius 26 radius 27 bmd 26 radius 38 total 27 bmd 30 = 27 bmd 38 total 28 ( 30 = 29 r 30 = 30 = 31 0.35 31 0.35 34 < 33 p 34 < 34 < 35 0.001 34 < 36 ) 38 total 40 bmd 38 total 47 < 38 total 50 while 39 radius 40 bmd 40 bmd 43 = 41 ( 43 = 42 r 43 = 43 = 44 0.48 46 p 47 < 47 < 48 0.001 47 < 49 ) 50 while 51 age 50 while 54 correlated 51 age 52 was 52 was 53 negatively 52 was 54 correlated 54 correlated 55 to 54 correlated 60 = 55 to 57 bmd 56 ud 57 bmd 58 ( 60 = 59 r 60 = 60 = 62 0.42 61 - 62 0.42 62 0.42 65 < 64 p 65 < 65 < 66 0.001 66 0.001 75 - 68 )(, 75 - 69 1/3 71 bmd 70 radius 71 bmd 71 bmd 74 = 72 ( 74 = 73 r 74 = 74 = 75 - 75 - 76 0.52 76 0.52 79 < 78 p 79 < 79 < 85 bmd 80 0.001 85 bmd 83 total 85 bmd 84 radius 85 bmd 85 bmd 89 - 86 ( 89 - 87 r 88 = 88 = 89 - 89 - 90 0.42 89 - 96 . 90 0.42 93 < 92 p 93 < 93 < 94 0.001 93 < 95 ) using multiple linear regression analysis models , age and weight explained 36 % , 41 [%] and 42 of the ud radius bmd , 1/3 radius bmd and total radius bmd variances respectively . 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 11 explained 0 ###LEFT-WALL### 24 , 0 ###LEFT-WALL### 34 . 1 using 6 models 1 using 7 , 1 using 9 and 2 multiple 5 analysis 3 linear 4 regression 4 regression 5 analysis 5 analysis 6 models 8 age 9 and 9 and 10 weight 9 and 11 explained 11 explained 13 % 12 36 13 % 13 % 17 and 14 , 17 and 15 41 17 and 17 and 18 42 17 and 19 of 17 and 24 , 19 of 23 bmd 20 the 23 bmd 21 ud 22 radius 22 radius 23 bmd 24 , 28 and 25 1/3 27 bmd 26 radius 27 bmd 27 bmd 28 and 28 and 30 radius 28 and 31 bmd 28 and 32 variances 29 total 30 radius 31 bmd 32 variances 32 variances 33 respectively ud radius bmd , 1/3 radius bmd and total radius bmd values were significantly different among the three groups ( p < 0.001 ) . 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 13 were 0 ###LEFT-WALL### 25 . 1 ud 2 radius 2 radius 3 bmd 3 bmd 4 , 4 , 7 bmd 4 , 8 and 5 1/3 7 bmd 6 radius 7 bmd 8 and 10 radius 8 and 11 bmd 8 and 12 values 8 and 13 were 9 total 10 radius 11 bmd 12 values 13 were 15 different 14 significantly 15 different 15 different 16 among 15 different 22 < 16 among 19 groups 17 the 18 three 18 three 19 groups 20 ( 22 < 21 p 22 < 22 < 23 0.001 22 < 24 ) ud radius bmd , 1/3 radius bmd and total radius bmd values were higher in obese and overweight women compared to normal - weight women ( p < 0.001 ) and in obese women compared to overweight women ( p < 0.001 ) . 0 ###LEFT-WALL### 3 bmd 0 ###LEFT-WALL### 4 , 0 ###LEFT-WALL### 44 . 1 ud 2 radius 2 radius 3 bmd 4 , 8 and 5 1/3 7 bmd 6 radius 7 bmd 7 bmd 8 and 8 and 10 radius 8 and 12 values 8 and 13 were 9 total 10 radius 11 bmd 12 values 12 values 13 were 13 were 14 higher 13 were 15 in 13 were 31 and 13 were 41 < 15 in 19 women 16 obese 17 and 17 and 18 overweight 17 and 19 women 19 women 20 compared 21 to 25 women 21 to 31 and 22 normal 23 - 22 normal 24 weight 24 weight 25 women 25 women 28 < 26 ( 28 < 27 p 28 < 28 < 29 0.001 28 < 30 ) 31 and 32 in 32 in 34 women 33 obese 34 women 34 women 35 compared 35 compared 36 to 36 to 38 women 37 overweight 38 women 39 ( 41 < 40 p 41 < 41 < 42 0.001 41 < 43 ) these differences among the three groups remained significant after adjusting for age and height ( p < 0.001 ) . 0 ###LEFT-WALL### 2 differences 0 ###LEFT-WALL### 7 remained 0 ###LEFT-WALL### 20 . 1 these 2 differences 2 differences 3 among 2 differences 7 remained 3 among 6 groups 4 the 5 three 5 three 6 groups 7 remained 8 significant 8 significant 9 after 9 after 10 adjusting 10 adjusting 11 for 11 for 13 and 12 age 13 and 13 and 14 height 13 and 17 < 15 ( 17 < 16 p 17 < 17 < 18 0.001 17 < 19 ) this study suggests that obesity is associated with higher ud radius , 1/3 radius and total radius bmd values in lebanese women . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 suggests 0 ###LEFT-WALL### 23 . 1 this 2 study 2 study 3 suggests 3 suggests 4 that 4 that 5 obesity 4 that 19 values 5 obesity 6 is 6 is 7 associated 7 associated 8 with 8 with 15 and 9 higher 11 radius 10 ud 11 radius 11 radius 12 , 12 , 14 radius 12 , 15 and 13 1/3 14 radius 15 and 17 radius 15 and 18 bmd 15 and 19 values 16 total 17 radius 18 bmd 19 values 19 values 20 in 20 in 22 women 21 lebanese 22 women thus , obesity seems to be protective against forearm osteopenia in lebanese women . 0 ###LEFT-WALL### 3 obesity 0 ###LEFT-WALL### 4 seems 0 ###LEFT-WALL### 14 . 1 thus 2 , 1 thus 3 obesity 3 obesity 4 seems 4 seems 5 to 4 seems 6 be 5 to 6 be 6 be 7 protective 7 protective 8 against 7 protective 11 in 8 against 10 osteopenia 9 forearm 10 osteopenia 11 in 13 women 12 lebanese 13 women elderly humans show decreased humoral immunity to pathogens and vaccines , yet the effects of aging on b cells are not fully known . 0 ###LEFT-WALL### 2 humans 0 ###LEFT-WALL### 3 show 0 ###LEFT-WALL### 11 , 0 ###LEFT-WALL### 24 . 1 elderly 2 humans 2 humans 3 show 3 show 6 immunity 3 show 7 to 4 decreased 6 immunity 5 humoral 6 immunity 7 to 9 and 8 pathogens 9 and 9 and 10 vaccines 11 , 12 yet 11 , 23 known 12 yet 14 effects 13 the 14 effects 14 effects 15 of 14 effects 20 are 15 of 16 aging 16 aging 17 on 16 aging 19 cells 17 on 18 b 20 are 21 not 20 are 23 known 22 fully 23 known chronic viral infection by cmv is implicated as a driver of clonal [t] cell proliferations in some aging humans , but whether [cmv] or ebv infection contributes to alterations in the [b] cell repertoire with age is unclear . 0 ###LEFT-WALL### 3 infection 0 ###LEFT-WALL### 7 implicated 0 ###LEFT-WALL### 21 but 0 ###LEFT-WALL### 39 . 1 chronic 3 infection 2 viral 3 infection 3 infection 4 by 3 infection 6 is 4 by 5 cmv 6 is 7 implicated 7 implicated 8 as 7 implicated 16 in 8 as 10 driver 9 a 10 driver 10 driver 11 of 11 of 15 proliferations 12 clonal 14 cell 14 cell 15 proliferations 16 in 19 humans 17 some 19 humans 18 aging 19 humans 20 , 21 but 21 but 24 or 21 but 37 is 22 whether 24 or 24 or 25 ebv 24 or 26 infection 24 or 27 contributes 24 or 37 is 26 infection 27 contributes 27 contributes 28 to 28 to 29 alterations 29 alterations 30 in 29 alterations 35 with 30 in 34 repertoire 31 the 34 repertoire 33 cell 34 repertoire 35 with 36 age 37 is 38 unclear we have used high - throughput dna sequencing of igh gene rearrangements to study the bcr repertoires over two successive years in 27 individuals ranging in age from 20 to 89 [y] . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 used 0 ###LEFT-WALL### 33 . 1 we 2 have 2 have 3 used 3 used 8 sequencing 3 used 13 to 3 used 14 study 4 high 5 - 4 high 6 throughput 6 throughput 8 sequencing 7 dna 8 sequencing 8 sequencing 9 of 9 of 12 rearrangements 10 igh 11 gene 11 gene 12 rearrangements 13 to 14 study 14 study 17 repertoires 14 study 18 over 14 study 22 in 14 study 26 in 15 the 17 repertoires 16 bcr 17 repertoires 18 over 21 years 19 two 21 years 20 successive 21 years 22 in 24 individuals 23 27 24 individuals 24 individuals 25 ranging 26 in 27 age 27 age 30 to 28 from 30 to 29 20 30 to 30 to 31 89 some features of the [b] cell repertoire remain stable with age , but elderly subjects show increased numbers of b cells with long cdr3 regions , a trend toward accumulation of more highly mutated igm and igg ig genes , and persistent clonal [b] cell populations in the blood . 0 ###LEFT-WALL### 2 features 0 ###LEFT-WALL### 8 remain 0 ###LEFT-WALL### 13 but 0 ###LEFT-WALL### 50 . 1 some 2 features 2 features 3 of 2 features 8 remain 3 of 7 repertoire 4 the 7 repertoire 6 cell 7 repertoire 8 remain 9 stable 9 stable 10 with 10 with 11 age 12 , 13 but 13 but 15 subjects 13 but 16 show 14 elderly 15 subjects 15 subjects 16 show 16 show 18 numbers 16 show 41 and 16 show 47 in 17 increased 18 numbers 18 numbers 19 of 19 of 20 b 21 cells 22 with 21 cells 26 , 22 with 25 regions 23 long 25 regions 24 cdr3 25 regions 26 , 28 trend 26 , 36 and 27 a 28 trend 28 trend 29 toward 29 toward 30 accumulation 30 accumulation 31 of 31 of 35 igm 32 more 34 mutated 33 highly 34 mutated 34 mutated 35 igm 36 and 39 genes 36 and 41 and 37 igg 38 ig 38 ig 39 genes 40 , 41 and 41 and 46 populations 42 persistent 45 cell 43 clonal 45 cell 45 cell 46 populations 47 in 49 blood 48 the 49 blood seropositivity for cmv or ebv infection alters [b] cell repertoires , regardless of the individual 's age : ebv infection correlates with the presence of persistent clonal [b] cell expansions , whereas cmv infection correlates with the proportion of highly mutated ab genes . 0 ###LEFT-WALL### 4 or 0 ###LEFT-WALL### 7 alters 0 ###LEFT-WALL### 18 : 0 ###LEFT-WALL### 44 . 1 seropositivity 2 for 1 seropositivity 4 or 2 for 3 cmv 4 or 6 infection 4 or 7 alters 5 ebv 6 infection 7 alters 10 repertoires 7 alters 13 of 9 cell 10 repertoires 11 , 13 of 12 regardless 13 of 13 of 17 age 13 of 18 : 14 the 15 individual 15 individual 16 's 16 's 17 age 18 : 19 ebv 18 : 31 , 19 ebv 20 infection 19 ebv 21 correlates 19 ebv 25 of 20 infection 21 correlates 21 correlates 22 with 22 with 24 presence 23 the 24 presence 25 of 30 expansions 26 persistent 29 cell 27 clonal 29 cell 29 cell 30 expansions 31 , 34 infection 31 , 35 correlates 32 whereas 33 cmv 32 whereas 34 infection 34 infection 35 correlates 35 correlates 36 with 36 with 38 proportion 37 the 38 proportion 38 proportion 39 of 39 of 43 genes 40 highly 41 mutated 41 mutated 43 genes 42 ab 43 genes these findings isolate effects of aging from those of chronic viral infection on b cell repertoires and provide a baseline for understanding human b cell responses to vaccination or infectious stimuli . 0 ###LEFT-WALL### 2 findings 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 32 . 1 these 2 findings 2 findings 17 and 3 isolate 4 effects 3 isolate 17 and 4 effects 5 of 5 of 6 aging 6 aging 7 from 6 aging 13 on 6 aging 16 repertoires 7 from 8 those 8 those 9 of 9 of 12 infection 10 chronic 12 infection 11 viral 12 infection 13 on 14 b 15 cell 16 repertoires 17 and 18 provide 18 provide 20 baseline 18 provide 21 for 19 a 20 baseline 21 for 22 understanding 22 understanding 26 responses 22 understanding 27 to 23 human 24 b 23 human 26 responses 25 cell 26 responses 27 to 29 or 28 vaccination 29 or 29 or 31 stimuli 30 infectious 31 stimuli background : as the general population is aging , surgery in elderly patients has become a major public health issue . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 10 surgery 2 : 15 become 2 : 21 . 3 as 6 population 3 as 8 aging 3 as 9 , 3 as 10 surgery 4 the 6 population 5 general 6 population 6 population 7 is 7 is 8 aging 8 aging 9 , 10 surgery 11 in 10 surgery 14 has 11 in 13 patients 12 elderly 13 patients 14 has 15 become 15 become 20 issue 16 a 17 major 16 a 20 issue 17 major 18 public 18 public 20 issue 19 health 20 issue this basic question is especially true for liver resection ( lr ) . 0 ###LEFT-WALL### 3 question 0 ###LEFT-WALL### 4 is 0 ###LEFT-WALL### 13 . 1 this 3 question 2 basic 3 question 3 question 4 is 4 is 6 true 5 especially 6 true 6 true 7 for 7 for 9 resection 8 liver 9 resection 9 resection 11 lr 10 ( 11 lr 11 lr 12 ) the aim of this study was to evaluate the operative risks of lr in the elderly . 0 ###LEFT-WALL### 2 aim 0 ###LEFT-WALL### 17 . 1 the 2 aim 2 aim 3 of 2 aim 6 was 3 of 5 study 4 this 5 study 6 was 7 to 6 was 8 evaluate 7 to 8 evaluate 8 evaluate 11 risks 8 evaluate 14 in 9 the 11 risks 10 operative 11 risks 11 risks 12 of 12 of 13 lr 14 in 16 elderly 15 the 16 elderly methods : retrospective analysis of a large recent and monocentric database of lr was performed between january 1 , 2005 and may [31] , 2011 . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 4 analysis 2 : 15 performed 2 : 19 , 2 : 26 . 3 retrospective 4 analysis 4 analysis 5 of 4 analysis 12 of 4 analysis 14 was 5 of 11 database 6 a 7 large 6 a 11 database 7 large 11 database 8 recent 9 and 9 and 10 monocentric 9 and 11 database 12 of 13 lr 14 was 15 performed 15 performed 16 between 16 between 17 january 17 january 18 1 19 , 22 may 19 , 24 , 20 2005 21 and 21 and 22 may 24 , 25 2011 patients were categorized into three groups ( < 60 , 60 - 74 , [and] ≥75 years old ) to analyze postoperative outcomes and 1 [-] year mortality . 0 ###LEFT-WALL### 1 patients 0 ###LEFT-WALL### 3 categorized 0 ###LEFT-WALL### 29 . 1 patients 2 were 2 were 3 categorized 3 categorized 4 into 3 categorized 20 to 4 into 6 groups 5 three 6 groups 6 groups 9 60 6 groups 12 - 6 groups 16 ≥75 7 ( 9 60 8 < 9 60 9 60 10 , 10 , 12 - 11 60 12 - 12 - 13 74 12 - 14 , 14 , 16 ≥75 16 ≥75 18 old 16 ≥75 19 ) 17 years 18 old 20 to 21 analyze 21 analyze 24 and 22 postoperative 23 outcomes 23 outcomes 24 and 24 and 28 mortality 25 1 27 year 27 year 28 mortality clinicopathologic factors likely to influence outcomes were assessed by univariate and multivariate analysis . 0 ###LEFT-WALL### 2 factors 0 ###LEFT-WALL### 8 assessed 0 ###LEFT-WALL### 14 . 1 clinicopathologic 2 factors 2 factors 3 likely 2 factors 7 were 3 likely 4 to 3 likely 5 influence 4 to 5 influence 5 influence 6 outcomes 7 were 8 assessed 8 assessed 9 by 9 by 11 and 10 univariate 11 and 11 and 13 analysis 12 multivariate 13 analysis results : altogether , 1,001 consecutive lrs were performed in 912 patients ( mean age 62 ± 13 years ) . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 7 lrs 2 : 9 performed 2 : 21 . 3 altogether 4 , 3 altogether 7 lrs 5 1,001 7 lrs 6 consecutive 7 lrs 7 lrs 8 were 8 were 9 performed 9 performed 10 in 10 in 12 patients 11 912 12 patients 12 patients 19 years 13 ( 19 years 14 mean 15 age 15 age 19 years 16 62 19 years 17 ± 19 years 18 13 19 years 19 years 20 ) the distribution of the lr by age was 372 ( 37.2 % ) , 477 ( 47.6 % ) , [and] 152 ( 15.2 % ) in [patients] < 60 , 60 - 74 , [and] ≥75 years , respectively . 0 ###LEFT-WALL### 2 distribution 0 ###LEFT-WALL### 8 was 0 ###LEFT-WALL### 41 . 1 the 2 distribution 2 distribution 3 of 2 distribution 8 was 3 of 5 lr 4 the 5 lr 5 lr 6 by 6 by 7 age 8 was 9 372 8 was 27 in 8 was 33 - 8 was 40 respectively 9 372 12 % 9 372 15 477 9 372 22 152 10 ( 12 % 11 37.2 12 % 12 % 13 ) 14 , 15 477 15 477 18 % 15 477 20 , 16 ( 18 % 17 47.6 18 % 18 % 19 ) 20 , 22 152 22 152 25 % 22 152 26 ) 23 ( 25 % 24 15.2 25 % 25 % 26 ) 27 in 30 60 29 < 30 60 31 , 33 - 32 60 33 - 33 - 34 74 33 - 39 , 34 74 38 years 35 , 38 years 37 ≥75 38 years 38 years 39 , the overall morbidity and mortality rates were 33.3 and 2.5 % , respectively . 0 ###LEFT-WALL### 6 rates 0 ###LEFT-WALL### 7 were 1 the 3 morbidity 2 overall 3 morbidity 3 morbidity 4 and 4 and 5 mortality 4 and 6 rates 6 rates 7 were 7 were 11 % 7 were 13 respectively 8 33.3 9 and 9 and 10 2.5 9 and 11 % 12 , 13 respectively 13 respectively 14 . age ≥75 years [was] independently associated with postoperative mortality [ odds [ratio] ( or ) 4.75 , 95 % confidence [interval] ( ci ) 1.5 - 15.1 [;] p = 0.008 ] and 1 [-] year mortality ( or 2.8 , 95 % ci 1.2 - 6.6 [;] p = 0.015 ) . 0 ###LEFT-WALL### 1 age 0 ###LEFT-WALL### 53 . 1 age 33 and 2 ≥75 3 years 3 years 6 associated 3 years 33 and 5 independently 6 associated 6 associated 7 with 7 with 9 mortality 7 with 16 4.75 8 postoperative 9 mortality 9 mortality 11 odds 10 [ 11 odds 11 odds 14 or 11 odds 15 ) 13 ( 14 or 14 or 15 ) 16 4.75 20 confidence 17 , 20 confidence 18 95 19 % 19 % 20 confidence 20 confidence 23 ci 20 confidence 30 = 20 confidence 32 ] 22 ( 23 ci 23 ci 24 ) 25 1.5 26 - 26 - 27 15.1 26 - 30 = 29 p 30 = 30 = 31 0.008 33 and 37 mortality 33 and 39 or 33 and 44 ci 34 1 36 year 36 year 37 mortality 38 ( 39 or 39 or 40 2.8 39 or 41 , 41 , 44 ci 42 95 44 ci 43 % 44 ci 44 ci 50 = 44 ci 52 ) 45 1.2 46 - 46 - 47 6.6 46 - 50 = 49 p 50 = 50 = 51 0.015 the postoperative complication rate ( p = 0.216 ) was not increased , even for major complications ( p = 0.09 ) . 0 ###LEFT-WALL### 4 rate 0 ###LEFT-WALL### 10 was 0 ###LEFT-WALL### 23 . 1 the 4 rate 2 postoperative 3 complication 3 complication 4 rate 4 rate 7 = 4 rate 10 was 5 ( 7 = 6 p 7 = 7 = 8 0.216 7 = 9 ) 10 was 11 not 10 was 14 even 11 not 12 increased 12 increased 13 , 14 even 15 for 15 for 17 complications 16 major 17 complications 17 complications 20 = 18 ( 20 = 19 p 20 = 20 = 21 0.09 20 = 22 ) the other independent risk factors for mortality were a cirrhotic liver ( p = 0.017 ) , preoperative arterial chemoembolization ( p = 0.001 ) , caval [vein] [clamping] ( p = 0.001 ) , and [intraoperative] blood transfusion ( p = 0.044 ) . 0 ###LEFT-WALL### 5 factors 0 ###LEFT-WALL### 36 and 0 ###LEFT-WALL### 45 . 1 the 2 other 2 other 5 factors 3 independent 5 factors 4 risk 5 factors 5 factors 6 for 5 factors 36 and 6 for 7 mortality 8 were 11 liver 8 were 36 and 9 a 11 liver 10 cirrhotic 11 liver 11 liver 14 = 11 liver 20 chemoembolization 11 liver 27 caval 12 ( 14 = 13 p 14 = 14 = 15 0.017 14 = 16 ) 17 , 20 chemoembolization 18 preoperative 20 chemoembolization 19 arterial 20 chemoembolization 20 chemoembolization 23 = 20 chemoembolization 25 ) 21 ( 23 = 22 p 23 = 23 = 24 0.001 23 = 25 ) 26 , 27 caval 27 caval 32 = 27 caval 34 ) 30 ( 32 = 31 p 32 = 32 = 33 0.001 35 , 36 and 36 and 38 blood 36 and 42 = 38 blood 39 transfusion 40 ( 42 = 41 p 42 = 42 = 43 0.044 42 = 44 ) conclusions : age beyond 75 years represent a risk factor of death after lr and should be avoided after chemoembolization or in cirrhotic patients . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 3 age 0 ###LEFT-WALL### 25 . 1 conclusions 2 : 2 : 3 age 3 age 4 beyond 3 age 21 or 4 beyond 5 75 5 75 6 years 5 75 15 and 6 years 15 and 7 represent 10 factor 7 represent 13 after 7 represent 15 and 8 a 10 factor 9 risk 10 factor 10 factor 11 of 11 of 12 death 13 after 14 lr 15 and 16 should 16 should 17 be 17 be 18 avoided 19 after 20 chemoembolization 19 after 21 or 21 or 22 in 22 in 24 patients 23 cirrhotic 24 patients a specific assessment using geriatric indexes might be the key to success in this population . 0 ###LEFT-WALL### 3 assessment 0 ###LEFT-WALL### 8 be 0 ###LEFT-WALL### 16 . 1 a 2 specific 1 a 3 assessment 2 specific 3 assessment 3 assessment 4 using 3 assessment 7 might 4 using 6 indexes 5 geriatric 6 indexes 7 might 8 be 8 be 10 key 9 the 10 key 10 key 11 to 11 to 12 success 12 success 13 in 13 in 15 population 14 this 15 population rationale : black box warnings for young adults under the age of 25 years indicate that antidepressants may increase risk of suicide . 0 ###LEFT-WALL### 1 rationale 0 ###LEFT-WALL### 2 : 2 : 5 warnings 2 : 15 indicate 2 : 23 . 3 black 4 box 4 box 5 warnings 5 warnings 6 for 5 warnings 9 under 5 warnings 15 indicate 6 for 8 adults 7 young 8 adults 9 under 11 age 10 the 11 age 11 age 12 of 12 of 14 years 13 25 14 years 15 indicate 16 that 16 that 17 antidepressants 16 that 19 increase 17 antidepressants 18 may 18 may 19 increase 19 increase 20 risk 20 risk 21 of 21 of 22 suicide while underlying mechanisms for age - related treatment effects remain unclear , vagally mediated cardiovascular function [may] play [a] key role . 0 ###LEFT-WALL### 10 remain 0 ###LEFT-WALL### 12 , 0 ###LEFT-WALL### 22 . 1 while 2 underlying 1 while 6 - 1 while 10 remain 2 underlying 3 mechanisms 3 mechanisms 4 for 4 for 5 age 6 - 7 related 7 related 9 effects 7 related 10 remain 8 treatment 9 effects 10 remain 11 unclear 12 , 21 role 13 vagally 14 mediated 14 mediated 16 function 15 cardiovascular 16 function 16 function 18 play 18 play 21 role 20 key 21 role decreased heart rate [(] hr [ )(and an increase in its variability ( hrv ) improve one 's capacity to adapt to environmental stress and attenuate risk for suicide . 0 ###LEFT-WALL### 7 )(and 0 ###LEFT-WALL### 25 and 0 ###LEFT-WALL### 30 . 1 decreased 2 heart 2 heart 3 rate 3 rate 5 hr 5 hr 7 )(and 7 )(and 9 increase 7 )(and 10 in 7 )(and 25 and 8 an 9 increase 10 in 12 variability 11 its 12 variability 12 variability 14 hrv 13 ( 14 hrv 14 hrv 15 ) 16 improve 19 capacity 16 improve 25 and 17 one 18 's 18 's 19 capacity 19 capacity 20 to 19 capacity 21 adapt 20 to 21 adapt 21 adapt 22 to 22 to 24 stress 23 environmental 24 stress 25 and 26 attenuate 25 and 28 for 26 attenuate 27 risk 28 for 29 suicide objectives : using a double blind , randomized , [placebo] - controlled , crossover , experimental study , we examine whether a single dose of escitalopram ( 20 mg ) attenuates cardiovascular responses to stress under experimental conditions and determine whether age moderates these effects . 0 ###LEFT-WALL### 1 objectives 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 13 , 0 ###LEFT-WALL### 46 . 1 objectives 2 : 2 : 3 using 2 : 6 blind 3 using 5 double 4 a 5 double 6 blind 8 randomized 6 blind 12 controlled 7 , 8 randomized 8 randomized 9 , 11 - 12 controlled 12 controlled 13 , 13 , 14 crossover 13 , 15 , 15 , 17 study 15 , 18 , 16 experimental 17 study 18 , 19 we 18 , 39 and 19 we 39 and 20 examine 21 whether 20 examine 39 and 21 whether 24 dose 21 whether 31 attenuates 22 a 24 dose 23 single 24 dose 24 dose 25 of 24 dose 31 attenuates 25 of 26 escitalopram 26 escitalopram 29 mg 27 ( 29 mg 28 20 29 mg 29 mg 30 ) 31 attenuates 33 responses 31 attenuates 34 to 31 attenuates 36 under 32 cardiovascular 33 responses 34 to 35 stress 36 under 38 conditions 37 experimental 38 conditions 39 and 40 determine 40 determine 41 whether 41 whether 42 age 41 whether 43 moderates 42 age 43 moderates 43 moderates 45 effects 44 these 45 effects methods : forty - four healthy females received a single dose of escitalopram ( 20 mg ) and placebo treatment separated by a 1 [-] week interval ( >5 [half] - lives ) . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 7 females 2 : 8 received 2 : 18 and 2 : 34 . 3 forty 4 - 4 - 5 four 4 - 7 females 6 healthy 7 females 7 females 8 received 8 received 11 dose 9 a 11 dose 10 single 11 dose 11 dose 12 of 11 dose 16 mg 12 of 13 escitalopram 14 ( 16 mg 15 20 16 mg 16 mg 17 ) 18 and 20 treatment 18 and 21 separated 19 placebo 20 treatment 20 treatment 21 separated 21 separated 22 by 22 by 27 interval 23 a 27 interval 24 1 26 week 26 week 27 interval 27 interval 32 lives 28 ( 32 lives 29 >5 31 - 29 >5 32 lives 32 lives 33 ) hr and high frequency hrv ( hf hrv normalized units ; 0.15 - 0.40 hz ) were measured during resting state [and] stress . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 11 ; 0 ###LEFT-WALL### 24 . 1 hr 2 and 2 and 10 units 3 high 4 frequency 4 frequency 9 normalized 5 hrv 7 hf 6 ( 7 hf 7 hf 8 hrv 8 hrv 9 normalized 9 normalized 10 units 11 ; 12 0.15 11 ; 18 measured 12 0.15 15 hz 12 0.15 17 were 13 - 15 hz 14 0.40 15 hz 15 hz 16 ) 17 were 18 measured 18 measured 19 during 19 during 23 stress 20 resting 23 stress 21 state 23 stress results : while escitalopram attenuated the increase in hr and increased hf hrv , these moderate [to] large effects were only significant in participants over 25 years of age . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 30 . 2 : 19 effects 2 : 20 were 3 while 4 escitalopram 3 while 14 , 3 while 19 effects 4 escitalopram 10 and 5 attenuated 7 increase 5 attenuated 8 in 5 attenuated 10 and 6 the 7 increase 8 in 9 hr 10 and 11 increased 11 increased 13 hrv 12 hf 13 hrv 15 these 19 effects 16 moderate 19 effects 18 large 19 effects 19 effects 20 were 20 were 21 only 20 were 22 significant 22 significant 23 in 22 significant 25 over 23 in 24 participants 25 over 27 years 26 25 27 years 27 years 28 of 28 of 29 age no beneficial cardiovascular effects of escitalopram were observed in those under the age of 25 . 0 ###LEFT-WALL### 4 effects 0 ###LEFT-WALL### 8 observed 0 ###LEFT-WALL### 16 . 1 no 4 effects 2 beneficial 4 effects 3 cardiovascular 4 effects 4 effects 5 of 4 effects 7 were 5 of 6 escitalopram 7 were 8 observed 8 observed 9 in 8 observed 11 under 9 in 10 those 11 under 13 age 12 the 13 age 13 age 14 of 14 of 15 25 conclusions : maturational differences in the development of the prefrontal cortex -- a critical region in the central network of autonomic control -- may underpin these differential findings . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 29 . 2 : 4 differences 2 : 25 underpin 3 maturational 4 differences 4 differences 5 in 4 differences 24 may 5 in 7 development 6 the 7 development 7 development 8 of 8 of 11 cortex 9 the 11 cortex 10 prefrontal 11 cortex 11 cortex 15 region 12 -- 15 region 13 a 14 critical 13 a 15 region 14 critical 15 region 15 region 16 in 15 region 23 -- 16 in 19 network 17 the 19 network 18 central 19 network 19 network 20 of 20 of 22 control 21 autonomic 22 control 24 may 25 underpin 25 underpin 28 findings 26 these 28 findings 27 differential 28 findings this study provides a theoretical framework on which future research on treatment - emergent suicidality in clinical populations could be based . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 provides 0 ###LEFT-WALL### 22 . 1 this 2 study 2 study 3 provides 3 provides 6 framework 4 a 5 theoretical 4 a 6 framework 5 theoretical 6 framework 6 framework 7 on 6 framework 21 based 7 on 8 which 7 on 10 research 7 on 15 suicidality 7 on 20 be 8 which 10 research 9 future 10 research 11 on 12 treatment 11 on 13 - 11 on 15 suicidality 14 emergent 15 suicidality 15 suicidality 16 in 15 suicidality 19 could 16 in 18 populations 17 clinical 18 populations 19 could 20 be background : adult height has been hypothesized to be inversely associated with coronary heart disease ; however , studies have produced conflicting results . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 9 be 2 : 16 ; 2 : 24 . 3 adult 4 height 4 height 5 has 5 has 6 been 6 been 7 hypothesized 7 hypothesized 8 to 8 to 9 be 9 be 10 inversely 9 be 11 associated 11 associated 12 with 12 with 15 disease 13 coronary 15 disease 14 heart 15 disease 16 ; 19 studies 16 ; 21 produced 17 however 18 , 17 however 19 studies 19 studies 20 have 20 have 21 produced 21 produced 23 results 22 conflicting 23 results we sought to examine the relationship between adult height and the prevalence of coronary artery calcium ( cac ) , a direct measure of subclinical atherosclerosis and surrogate marker of coronary heart disease . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 sought 0 ###LEFT-WALL### 20 , 0 ###LEFT-WALL### 34 . 1 we 2 sought 2 sought 3 to 2 sought 4 examine 3 to 4 examine 4 examine 6 relationship 4 examine 7 between 5 the 6 relationship 7 between 10 and 8 adult 9 height 9 height 10 and 10 and 12 prevalence 10 and 13 of 10 and 18 cac 11 the 12 prevalence 13 of 16 calcium 14 coronary 16 calcium 15 artery 16 calcium 17 ( 18 cac 18 cac 19 ) 20 , 27 and 21 a 23 measure 22 direct 23 measure 23 measure 24 of 23 measure 27 and 24 of 26 atherosclerosis 25 subclinical 26 atherosclerosis 27 and 29 marker 27 and 30 of 28 surrogate 29 marker 30 of 33 disease 31 coronary 33 disease 32 heart 33 disease methods and results : we evaluated the relationship between adult height and cac in 2703 participants from the national heart , lung , and blood institute family heart study who underwent cardiac computed tomography . 0 ###LEFT-WALL### 3 results 0 ###LEFT-WALL### 4 : 1 methods 2 and 2 and 3 results 4 : 5 we 4 : 6 evaluated 4 : 35 . 5 we 6 evaluated 6 evaluated 8 relationship 6 evaluated 9 between 6 evaluated 14 in 7 the 8 relationship 9 between 12 and 10 adult 11 height 11 height 12 and 12 and 13 cac 14 in 24 and 15 2703 16 participants 16 participants 17 from 16 participants 21 , 17 from 20 heart 18 the 20 heart 19 national 20 heart 21 , 22 lung 21 , 24 and 23 , 24 and 24 and 29 study 24 and 30 who 24 and 31 underwent 25 blood 26 institute 26 institute 27 family 27 family 28 heart 28 heart 29 study 30 who 31 underwent 31 underwent 34 tomography 32 cardiac 34 tomography 33 computed 34 tomography we used generalized estimating equations to calculate the prevalence odds ratios for the presence of cac ( cac>0 ) across sex - specific quartiles of height . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 used 1 we 2 used 2 used 5 equations 2 used 6 to 2 used 7 calculate 3 generalized 5 equations 4 estimating 5 equations 6 to 7 calculate 7 calculate 11 ratios 7 calculate 12 for 7 calculate 20 across 8 the 11 ratios 9 prevalence 11 ratios 10 odds 11 ratios 12 for 14 presence 13 the 14 presence 14 presence 15 of 15 of 16 cac 16 cac 18 cac>0 17 ( 18 cac>0 18 cac>0 19 ) 20 across 21 sex 21 sex 24 quartiles 22 - 24 quartiles 23 specific 24 quartiles 24 quartiles 25 of 24 quartiles 27 . 25 of 26 height the mean age of the sample was 54.8 years , and 60.2 % of participants were female . 0 ###LEFT-WALL### 3 age 0 ###LEFT-WALL### 7 was 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 18 . 1 the 3 age 2 mean 3 age 3 age 4 of 3 age 7 was 4 of 6 sample 5 the 6 sample 7 was 9 years 8 54.8 9 years 10 , 11 and 11 and 13 % 11 and 16 were 12 60.2 13 % 13 % 14 of 13 % 16 were 14 of 15 participants 16 were 17 female there was an inverse association between adult height and cac . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 was 0 ###LEFT-WALL### 11 . 1 there 2 was 2 was 5 association 2 was 6 between 3 an 4 inverse 3 an 5 association 4 inverse 5 association 6 between 9 and 7 adult 8 height 8 height 9 and 9 and 10 cac after adjusting for age , race , field center , waist circumference , smoking , alcohol , physical activity , systolic blood pressure , antihypertensive medications , diabetes mellitus , diabetic medications , low - density lipoprotein cholesterol , high - density lipoprotein cholesterol , lipid [-] lowering medications , and income , individuals in the tallest quartile had 30 % lower odds of having prevalent cac . 0 ###LEFT-WALL### 51 and 0 ###LEFT-WALL### 59 had 0 ###LEFT-WALL### 68 . 1 after 2 adjusting 1 after 5 , 1 after 51 and 2 adjusting 3 for 3 for 4 age 6 race 7 , 7 , 9 center 7 , 10 , 8 field 9 center 10 , 12 circumference 10 , 13 , 11 waist 12 circumference 13 , 14 smoking 13 , 15 , 15 , 16 alcohol 15 , 17 , 17 , 19 activity 17 , 20 , 18 physical 19 activity 20 , 23 pressure 20 , 24 , 21 systolic 22 blood 22 blood 23 pressure 24 , 26 medications 24 , 27 , 25 antihypertensive 26 medications 27 , 29 mellitus 27 , 30 , 28 diabetes 29 mellitus 30 , 32 medications 30 , 33 , 31 diabetic 32 medications 33 , 38 cholesterol 33 , 39 , 34 low 35 - 34 low 38 cholesterol 36 density 38 cholesterol 37 lipoprotein 38 cholesterol 39 , 49 medications 39 , 51 and 40 high 44 cholesterol 40 high 45 , 40 high 46 lipid 41 - 44 cholesterol 42 density 44 cholesterol 43 lipoprotein 44 cholesterol 44 cholesterol 45 , 46 lipid 49 medications 48 lowering 49 medications 50 , 51 and 51 and 52 income 51 and 53 , 51 and 54 individuals 51 and 58 quartile 51 and 59 had 54 individuals 55 in 54 individuals 58 quartile 55 in 57 tallest 56 the 57 tallest 59 had 63 odds 60 30 63 odds 61 % 63 odds 62 lower 63 odds 63 odds 64 of 64 of 65 having 65 having 67 cac 66 prevalent 67 cac there was no evidence of effect modification for the relationship between adult height and cac by age or socioeconomic status . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 was 0 ###LEFT-WALL### 21 . 1 there 2 was 2 was 4 evidence 2 was 11 between 3 no 4 evidence 4 evidence 5 of 5 of 7 modification 6 effect 7 modification 7 modification 8 for 8 for 10 relationship 9 the 10 relationship 11 between 18 or 12 adult 13 height 13 height 14 and 14 and 15 cac 14 and 16 by 14 and 18 or 16 by 17 age 18 or 20 status 19 socioeconomic 20 status conclusions : the results of our study suggest an inverse , independent association between adult height and cac . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 19 . 2 : 4 results 2 : 8 suggest 3 the 4 results 4 results 5 of 4 results 8 suggest 5 of 7 study 6 our 7 study 8 suggest 13 association 8 suggest 14 between 9 an 10 inverse 9 an 13 association 10 inverse 11 , 10 inverse 13 association 12 independent 13 association 14 between 17 and 15 adult 16 height 16 height 17 and 17 and 18 cac cardiac and peripheral vasomotor factors contribute to the rapid pressor response at the onset of isometric handgrip exercise . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 6 contribute 0 ###LEFT-WALL### 19 . 1 cardiac 2 and 2 and 5 factors 2 and 6 contribute 3 peripheral 4 vasomotor 4 vasomotor 5 factors 6 contribute 7 to 6 contribute 12 at 7 to 11 response 8 the 11 response 9 rapid 10 pressor 10 pressor 11 response 12 at 14 onset 13 the 14 onset 14 onset 15 of 15 of 18 exercise 16 isometric 17 handgrip 17 handgrip 18 exercise we tested the hypothesis that age enhances the sympathetic and vasoconstrictor response at the onset of isometric handgrip exercise so that the pressor response is maintained , despite a diminished cardiac function . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 tested 0 ###LEFT-WALL### 33 . 1 we 2 tested 2 tested 4 hypothesis 3 the 4 hypothesis 4 hypothesis 5 that 5 that 6 age 5 that 7 enhances 6 age 7 enhances 7 enhances 10 and 7 enhances 13 at 7 enhances 21 that 7 enhances 28 despite 8 the 10 and 9 sympathetic 10 and 10 and 12 response 11 vasoconstrictor 12 response 13 at 15 onset 14 the 15 onset 15 onset 16 of 16 of 19 exercise 17 isometric 19 exercise 18 handgrip 19 exercise 20 so 21 that 21 that 24 response 21 that 26 maintained 22 the 24 response 23 pressor 24 response 24 response 25 is 25 is 26 maintained 26 maintained 27 , 28 despite 32 function 29 a 32 function 30 diminished 32 function 31 cardiac 32 function [twelve] young and twelve older [(] 24 ± 3 and 63 ± 8 yr [ )(individuals performed 20 - s isometric handgrip exercise at 30 , 40 , or 50 % of maximal voluntary contraction force . 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 12 ± 0 ###LEFT-WALL### 37 . 2 young 3 and 3 and 8 ± 3 and 12 ± 4 twelve 8 ± 5 older 8 ± 7 24 8 ± 8 ± 10 and 9 3 10 and 10 and 11 63 12 ± 31 % 13 8 14 yr 13 8 29 or 14 yr 16 )(individuals 16 )(individuals 17 performed 17 performed 23 exercise 17 performed 24 at 18 20 19 - 19 - 20 s 19 - 23 exercise 21 isometric 22 handgrip 22 handgrip 23 exercise 24 at 25 30 25 30 27 40 26 , 27 40 27 40 28 , 29 or 30 50 29 or 31 % 31 % 32 of 32 of 36 force 33 maximal 34 voluntary 34 voluntary 36 force 35 contraction 36 force muscle sympathetic nerve activity ( msna ) was measured using microneurography . 0 ###LEFT-WALL### 4 activity 0 ###LEFT-WALL### 8 was 0 ###LEFT-WALL### 12 . 1 muscle 4 activity 2 sympathetic 3 nerve 3 nerve 4 activity 4 activity 6 msna 4 activity 8 was 5 ( 6 msna 6 msna 7 ) 8 was 9 measured 9 measured 10 using 10 using 11 microneurography mean arterial pressure ( map ) and cardiac output ( q ) were assessed continuously by finger plethysmography and total peripheral resistance was calculated . 0 ###LEFT-WALL### 1 mean 0 ###LEFT-WALL### 7 and 0 ###LEFT-WALL### 25 . 1 mean 3 pressure 2 arterial 3 pressure 3 pressure 5 map 4 ( 5 map 5 map 6 ) 7 and 9 output 7 and 14 assessed 8 cardiac 9 output 9 output 11 q 9 output 13 were 10 ( 11 q 11 q 12 ) 13 were 14 assessed 14 assessed 15 continuously 14 assessed 16 by 16 by 19 and 17 finger 18 plethysmography 18 plethysmography 19 and 19 and 20 total 19 and 22 resistance 19 and 23 was 19 and 24 calculated 21 peripheral 22 resistance 22 resistance 23 was map increased with the onset of handgrip ; this increase was associated with handgrip [intensity] and was similar in both groups . 0 ###LEFT-WALL### 1 map 0 ###LEFT-WALL### 2 increased 0 ###LEFT-WALL### 8 ; 0 ###LEFT-WALL### 22 . 1 map 2 increased 2 increased 3 with 3 with 5 onset 4 the 5 onset 5 onset 6 of 6 of 7 handgrip 8 ; 10 increase 8 ; 16 and 9 this 10 increase 10 increase 16 and 11 was 12 associated 11 was 16 and 12 associated 13 with 13 with 14 handgrip 16 and 17 was 17 was 18 similar 18 similar 19 in 19 in 21 groups 20 both 21 groups heart [rate] and q increased with increasing handgrip [intensity] in both groups , but increases were greater in young [vs] [.] older individuals ( age × handgrip intensity interaction , p < 0.05 ) . 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 5 increased 0 ###LEFT-WALL### 14 but 0 ###LEFT-WALL### 35 . 1 heart 3 and 3 and 4 q 3 and 5 increased 5 increased 6 with 6 with 7 increasing 7 increasing 8 handgrip 7 increasing 10 in 10 in 12 groups 11 both 12 groups 13 , 14 but 14 but 15 increases 14 but 16 were 15 increases 16 were 16 were 17 greater 17 greater 18 in 17 greater 32 < 18 in 23 individuals 19 young 22 older 22 older 23 individuals 23 individuals 29 interaction 24 ( 29 interaction 25 age 28 intensity 26 × 27 handgrip 27 handgrip 28 intensity 28 intensity 29 interaction 29 interaction 30 , 31 p 32 < 32 < 33 0.05 32 < 34 ) msna burst frequency increased ( p < 0.01 ) , while msna burst incidence tended to increase ( p = 0.06 ) with increasing handgrip [intensity] in both groups . 0 ###LEFT-WALL### 3 frequency 0 ###LEFT-WALL### 4 increased 0 ###LEFT-WALL### 10 , 0 ###LEFT-WALL### 30 . 1 msna 3 frequency 2 burst 3 frequency 3 frequency 4 increased 4 increased 7 < 5 ( 7 < 6 p 7 < 7 < 8 0.01 7 < 9 ) 10 , 25 handgrip 10 , 29 groups 11 while 15 tended 11 while 25 handgrip 12 msna 13 burst 13 burst 15 tended 14 incidence 15 tended 16 to 17 increase 16 to 22 ) 16 to 25 handgrip 17 increase 20 = 18 ( 20 = 19 p 20 = 20 = 21 0.06 23 with 24 increasing 23 with 25 handgrip 25 handgrip 27 in 25 handgrip 29 groups 27 in 28 both the change in msna between baseline and handgrip , for both frequency and incidence , increased with increasing handgrip [intensity] for both groups . 0 ###LEFT-WALL### 2 change 0 ###LEFT-WALL### 16 increased 0 ###LEFT-WALL### 24 . 1 the 2 change 2 change 3 in 2 change 10 for 2 change 16 increased 3 in 7 and 4 msna 5 between 4 msna 7 and 5 between 6 baseline 7 and 8 handgrip 9 , 10 for 10 for 13 and 10 for 15 , 11 both 13 and 12 frequency 13 and 13 and 14 incidence 16 increased 17 with 17 with 18 increasing 18 increasing 19 handgrip 19 handgrip 21 for 21 for 23 groups 22 both 23 groups there was no effect of handgrip [intensity] or age on total peripheral resistance . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 was 0 ###LEFT-WALL### 14 . 1 there 2 was 2 was 4 effect 3 no 4 effect 4 effect 5 of 5 of 8 or 6 handgrip 8 or 8 or 9 age 8 or 10 on 10 on 13 resistance 11 total 13 resistance 12 peripheral 13 resistance the smaller heart rate [and] q response during the first 20 [s] of handgrip exercise in older individuals was not accompanied by a greater sympathetic activation or vasoconstrictor response . 0 ###LEFT-WALL### 7 response 0 ###LEFT-WALL### 19 was 0 ###LEFT-WALL### 30 . 1 the 7 response 2 smaller 3 heart 3 heart 4 rate 4 rate 6 q 4 rate 7 response 7 response 8 during 7 response 13 of 7 response 19 was 8 during 11 20 9 the 10 first 9 the 11 20 13 of 15 exercise 14 handgrip 15 exercise 15 exercise 16 in 16 in 18 individuals 17 older 18 individuals 19 was 20 not 19 was 22 by 20 not 21 accompanied 22 by 29 response 23 a 29 response 24 greater 26 activation 25 sympathetic 26 activation 26 activation 27 or 27 or 28 vasoconstrictor 27 or 29 response however , increases in map were similar between groups , indicating that the pressor response at the onset of handgrip exercise is preserved with aging . 0 ###LEFT-WALL### 3 increases 0 ###LEFT-WALL### 6 were 1 however 2 , 1 however 3 increases 3 increases 4 in 3 increases 6 were 4 in 5 map 6 were 7 similar 7 similar 8 between 8 between 9 groups 9 groups 11 indicating 10 , 11 indicating 11 indicating 12 that 11 indicating 26 . 12 that 15 response 12 that 23 preserved 13 the 15 response 14 pressor 15 response 15 response 16 at 15 response 22 is 16 at 18 onset 17 the 18 onset 18 onset 19 of 19 of 21 exercise 20 handgrip 21 exercise 22 is 23 preserved 23 preserved 24 with 24 with 25 aging this article reviews the scientific literature on the enhancement of healthy aging in older adults through active participation in the arts . 0 ###LEFT-WALL### 2 article 0 ###LEFT-WALL### 3 reviews 0 ###LEFT-WALL### 22 . 1 this 2 article 2 article 3 reviews 3 reviews 6 literature 3 reviews 7 on 3 reviews 13 in 3 reviews 16 through 3 reviews 19 in 4 the 6 literature 5 scientific 6 literature 7 on 9 enhancement 8 the 9 enhancement 9 enhancement 10 of 10 of 12 aging 11 healthy 12 aging 13 in 15 adults 14 older 15 adults 16 through 18 participation 17 active 18 participation 19 in 21 arts 20 the 21 arts methodologies and conclusions are described for studies of dance , expressive writing , music ( singing and instrumental ) , theatre arts , and visual arts including documentation of mental/physical improvements in memory , creativity , problem solving , everyday competence , reaction time , balance/gait , and quality of life . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 5 described 0 ###LEFT-WALL### 34 , 0 ###LEFT-WALL### 52 . 1 methodologies 2 and 2 and 3 conclusions 2 and 4 are 4 are 5 described 5 described 6 for 6 for 7 studies 7 studies 8 of 8 of 9 dance 9 dance 12 writing 9 dance 14 music 9 dance 24 and 10 , 12 writing 11 expressive 12 writing 12 writing 13 , 13 , 14 music 14 music 17 and 14 music 20 , 15 ( 17 and 16 singing 17 and 17 and 18 instrumental 17 and 19 ) 20 , 24 and 21 theatre 22 arts 22 arts 24 and 23 , 24 and 24 and 26 arts 24 and 27 including 24 and 34 , 25 visual 26 arts 27 including 28 documentation 28 documentation 29 of 28 documentation 32 in 29 of 31 improvements 30 mental/physical 31 improvements 32 in 33 memory 34 , 48 and 35 creativity 36 , 36 , 38 solving 36 , 39 , 37 problem 38 solving 39 , 41 competence 39 , 42 , 40 everyday 41 competence 42 , 44 time 42 , 45 , 43 reaction 44 time 45 , 46 balance/gait 45 , 48 and 47 , 48 and 48 and 49 quality 48 and 50 of 50 of 51 life in addition to these gains in measures of successful aging , the article also provides ( in a supplementary appendix ) some selected examples of arts engagement for remedial purposes . 0 ###LEFT-WALL### 13 article 0 ###LEFT-WALL### 15 provides 0 ###LEFT-WALL### 31 . 1 in 2 addition 1 in 11 , 1 in 13 article 2 addition 3 to 3 to 5 gains 4 these 5 gains 5 gains 6 in 6 in 7 measures 7 measures 8 of 8 of 10 aging 9 successful 10 aging 12 the 13 article 13 article 15 provides 14 also 15 provides 15 provides 17 in 15 provides 24 examples 16 ( 17 in 17 in 20 appendix 17 in 21 ) 18 a 20 appendix 19 supplementary 20 appendix 22 some 24 examples 23 selected 24 examples 24 examples 25 of 25 of 27 engagement 26 arts 27 engagement 27 engagement 28 for 28 for 30 purposes 29 remedial 30 purposes finally , it offers suggestions for expanding inquiry into this underinvestigated corner of aging research . 0 ###LEFT-WALL### 3 it 0 ###LEFT-WALL### 4 offers 0 ###LEFT-WALL### 16 . 1 finally 2 , 1 finally 3 it 3 it 4 offers 4 offers 5 suggestions 5 suggestions 6 for 6 for 7 expanding 7 expanding 8 inquiry 7 expanding 9 into 9 into 12 corner 10 this 12 corner 11 underinvestigated 12 corner 12 corner 13 of 13 of 14 aging 14 aging 15 research memory and dementia are historical ideas that preceded the development of modern neuroscientific , psychogeriatric and medical approaches to aging and cognitive impairment . 0 ###LEFT-WALL### 1 memory 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 24 . 2 and 3 dementia 2 and 4 are 3 dementia 4 are 4 are 6 ideas 5 historical 6 ideas 6 ideas 7 that 6 ideas 8 preceded 7 that 8 preceded 8 preceded 10 development 8 preceded 19 to 9 the 10 development 10 development 11 of 11 of 18 approaches 12 modern 18 approaches 13 neuroscientific 14 , 13 neuroscientific 18 approaches 15 psychogeriatric 16 and 16 and 17 medical 16 and 18 approaches 19 to 21 and 20 aging 21 and 21 and 23 impairment 22 cognitive 23 impairment this article explores the value of such historical ideas in order to understand the discourses and metaphors by which western thought has individualized memory as the guarantor of rational personhood , while at the same , treating memory decline as a threat to healthy and successful aging . 0 ###LEFT-WALL### 2 article 0 ###LEFT-WALL### 3 explores 1 this 2 article 2 article 3 explores 3 explores 16 and 4 the 5 value 5 value 6 of 5 value 16 and 6 of 9 ideas 7 such 9 ideas 8 historical 9 ideas 9 ideas 10 in 10 in 11 order 11 order 12 to 11 order 13 understand 12 to 13 understand 13 understand 15 discourses 14 the 15 discourses 16 and 17 metaphors 16 and 18 by 18 by 19 which 18 by 20 western 18 by 21 thought 18 by 22 has 19 which 20 western 21 thought 22 has 22 has 24 memory 22 has 32 while 23 individualized 24 memory 24 memory 25 as 24 memory 28 of 25 as 27 guarantor 26 the 27 guarantor 28 of 30 personhood 29 rational 30 personhood 31 , 32 while 32 while 33 at 32 while 48 . 33 at 39 decline 34 the 35 same 34 the 39 decline 35 same 36 , 37 treating 39 decline 38 memory 39 decline 39 decline 40 as 40 as 42 threat 41 a 42 threat 42 threat 43 to 42 threat 47 aging 43 to 45 and 44 healthy 45 and 45 and 46 successful discussion focuses on the relationship between memory and the body in the classical and medieval ars memoria ( the art of memory ) and in the early modern philosophies of personhood , particularly the work of john locke . 0 ###LEFT-WALL### 1 discussion 0 ###LEFT-WALL### 2 focuses 1 discussion 2 focuses 2 focuses 3 on 2 focuses 6 between 3 on 5 relationship 4 the 5 relationship 6 between 8 and 7 memory 8 and 8 and 10 body 8 and 24 and 9 the 10 body 11 in 17 memoria 11 in 24 and 12 the 17 memoria 13 classical 14 and 14 and 15 medieval 14 and 17 memoria 16 ars 17 memoria 17 memoria 20 art 18 ( 20 art 19 the 20 art 20 art 21 of 20 art 23 ) 21 of 22 memory 24 and 25 in 25 in 29 philosophies 26 the 29 philosophies 27 early 29 philosophies 28 modern 29 philosophies 29 philosophies 30 of 30 of 31 personhood 31 personhood 35 work 32 , 33 particularly 32 , 35 work 34 the 35 work 35 work 36 of 35 work 39 . 36 of 38 locke 37 john 38 locke conclusions consider the significance of western culture 's history of embodied memory as it moved from cosmic to individual [to] neurocognitive sites for our wider views about the treatment of dementia . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 consider 0 ###LEFT-WALL### 32 . 1 conclusions 2 consider 2 consider 4 significance 2 consider 17 cosmic 3 the 4 significance 4 significance 5 of 5 of 6 western 6 western 9 history 6 western 16 from 7 culture 8 's 8 's 9 history 9 history 10 of 9 history 13 as 9 history 15 moved 10 of 12 memory 11 embodied 12 memory 13 as 14 it 15 moved 16 from 17 cosmic 18 to 17 cosmic 27 about 18 to 22 sites 19 individual 22 sites 21 neurocognitive 22 sites 22 sites 23 for 23 for 26 views 24 our 26 views 25 wider 26 views 27 about 29 treatment 28 the 29 treatment 29 treatment 30 of 30 of 31 dementia objectives : economic security around retirement age may be an important determinant of psychological and cognitive well - being of older adults . 0 ###LEFT-WALL### 1 objectives 0 ###LEFT-WALL### 9 be 1 objectives 2 : 2 : 4 security 3 economic 4 security 4 security 5 around 4 security 7 age 4 security 9 be 5 around 6 retirement 7 age 8 may 8 may 9 be 9 be 12 determinant 10 an 11 important 10 an 12 determinant 11 important 12 determinant 12 determinant 13 of 13 of 17 well 14 psychological 15 and 15 and 16 cognitive 15 and 17 well 17 well 19 being 18 - 19 being 19 being 20 of 19 being 23 . 20 of 22 adults 21 older 22 adults this study examines the impact of the dramatic increase in housing prices from the mid - 1990 s to the mid - 2000 s on psychological and cognitive outcomes among americans born between 1924 and 1960 . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 examines 0 ###LEFT-WALL### 16 - 0 ###LEFT-WALL### 37 . 1 this 2 study 2 study 3 examines 3 examines 5 impact 3 examines 10 in 3 examines 13 from 4 the 5 impact 5 impact 6 of 6 of 9 increase 7 the 9 increase 8 dramatic 9 increase 10 in 11 housing 11 housing 12 prices 13 from 15 mid 14 the 15 mid 16 - 18 s 16 - 22 - 17 1990 18 s 18 s 19 to 19 to 21 mid 20 the 21 mid 22 - 24 s 23 2000 24 s 24 s 25 on 25 on 29 outcomes 26 psychological 27 and 27 and 28 cognitive 27 and 29 outcomes 29 outcomes 30 among 29 outcomes 32 born 30 among 31 americans 32 born 33 between 33 between 35 and 34 1924 35 and 35 and 36 1960 method : our quasi - experimental empirical strategy exploits geographic differences in housing market price trends during the housing boom ( from the mid - [1990s] until 2006 ) . 0 ###LEFT-WALL### 1 method 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 30 . 2 : 4 quasi 2 : 5 - 2 : 16 trends 3 our 4 quasi 5 - 8 strategy 5 - 9 exploits 6 experimental 8 strategy 7 empirical 8 strategy 8 strategy 9 exploits 9 exploits 11 differences 10 geographic 11 differences 11 differences 12 in 12 in 13 housing 13 housing 15 price 13 housing 16 trends 14 market 15 price 15 price 16 trends 16 trends 17 during 16 trends 27 until 17 during 20 boom 18 the 20 boom 19 housing 20 boom 20 boom 22 from 21 ( 22 from 22 from 24 mid 22 from 25 - 23 the 24 mid 25 - 27 until 27 until 28 2006 27 until 29 ) we use individual - level data from the health and retirement study ( hrs ) and estimates of housing values from dataquick , a california - based real estate consultancy firm , to estimate the association of housing price increases with psychological and cognitive outcomes at follow - up . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 32 , 0 ###LEFT-WALL### 48 - 1 we 32 , 2 use 10 and 2 use 32 , 3 individual 4 - 3 individual 5 level 5 level 6 data 6 data 7 from 6 data 10 and 7 from 9 health 8 the 9 health 10 and 31 firm 11 retirement 12 study 12 study 14 hrs 13 ( 14 hrs 14 hrs 15 ) 14 hrs 16 and 16 and 17 estimates 16 and 25 california 16 and 27 based 17 estimates 18 of 18 of 20 values 19 housing 20 values 20 values 21 from 21 from 22 dataquick 23 , 25 california 24 a 25 california 25 california 26 - 27 based 31 firm 28 real 31 firm 29 estate 31 firm 30 consultancy 31 firm 32 , 33 to 32 , 47 follow 33 to 34 estimate 34 estimate 36 association 35 the 36 association 36 association 37 of 36 association 39 price 36 association 46 at 37 of 38 housing 39 price 40 increases 40 increases 41 with 40 increases 46 at 41 with 45 outcomes 42 psychological 43 and 43 and 44 cognitive 43 and 45 outcomes 48 - 49 up 48 - 50 . results : greater housing appreciation over the [follow] [-] up period was associated with a significantly lower risk of anxiety ( for women ) and an improved performance on some but not all cognitive tasks . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 4 housing 2 : 13 associated 2 : 36 . 3 greater 4 housing 4 housing 5 appreciation 4 housing 12 was 4 housing 13 associated 5 appreciation 6 over 5 appreciation 12 was 6 over 11 period 7 the 11 period 10 up 11 period 13 associated 14 with 13 associated 29 on 13 associated 31 but 14 with 25 and 15 a 18 risk 16 significantly 17 lower 17 lower 18 risk 18 risk 19 of 18 risk 25 and 19 of 20 anxiety 20 anxiety 22 for 21 ( 22 for 22 for 23 women 22 for 24 ) 25 and 28 performance 26 an 28 performance 27 improved 28 performance 29 on 30 some 31 but 35 tasks 32 not 33 all 33 all 35 tasks 34 cognitive 35 tasks effects for depressive symptoms , positive and negative [affect] , and life satisfaction were all in the beneficial direction but not statistically significant . 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 14 were 0 ###LEFT-WALL### 24 . 1 effects 2 for 1 effects 11 and 2 for 4 symptoms 3 depressive 4 symptoms 4 symptoms 7 and 5 , 7 and 6 positive 7 and 7 and 8 negative 7 and 10 , 11 and 13 satisfaction 11 and 14 were 12 life 13 satisfaction 14 were 20 but 15 all 16 in 15 all 20 but 16 in 19 direction 17 the 19 direction 18 beneficial 19 direction 20 but 21 not 20 but 23 significant 22 statistically 23 significant the effects of price run [-] [ups] were concentrated on homeowners , as opposed to renters , [suggestive] of wealth - driven effects . 0 ###LEFT-WALL### 2 effects 0 ###LEFT-WALL### 14 opposed 0 ###LEFT-WALL### 24 . 1 the 2 effects 2 effects 3 of 2 effects 8 were 3 of 4 price 4 price 5 run 8 were 9 concentrated 9 concentrated 10 on 9 concentrated 13 as 10 on 11 homeowners 12 , 13 as 13 as 14 opposed 14 opposed 15 to 14 opposed 23 effects 15 to 16 renters 16 renters 19 of 17 , 19 of 19 of 20 wealth 19 of 21 - 22 driven 23 effects discussion : housing market volatility may influence the psychological and cognitive health of older adults , highlighting potential health consequences of pro - home ownership policies , which may be especially important in light of recent dramatic housing price declines [.] 0 ###LEFT-WALL### 1 discussion 0 ###LEFT-WALL### 2 : 2 : 5 volatility 2 : 7 influence 3 housing 4 market 4 market 5 volatility 5 volatility 6 may 6 may 7 influence 7 influence 10 and 8 the 10 and 9 psychological 10 and 10 and 12 health 10 and 16 , 10 and 17 highlighting 10 and 21 of 11 cognitive 12 health 12 health 13 of 13 of 15 adults 14 older 15 adults 17 highlighting 20 consequences 18 potential 19 health 19 health 20 consequences 21 of 22 pro 22 pro 26 policies 22 pro 28 which 23 - 26 policies 24 home 26 policies 25 ownership 26 policies 26 policies 27 , 27 , 28 which 28 which 29 may 29 may 30 be 30 be 32 important 31 especially 32 important 32 important 33 in 33 in 34 light 34 light 35 of 35 of 40 declines 36 recent 40 declines 37 dramatic 39 price 38 housing 39 price 39 price 40 declines background : in spite of evidence that physical activity has beneficial effects on health and age - related functional decline , there is a scarcity of detailed and accurate information on objectively measured daily activity and patterns of such activity in older adults . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 4 spite 2 : 17 - 3 in 4 spite 4 spite 5 of 4 spite 13 on 5 of 6 evidence 6 evidence 7 that 7 that 9 activity 7 that 10 has 8 physical 9 activity 9 activity 10 has 10 has 12 effects 11 beneficial 12 effects 13 on 15 and 14 health 15 and 15 and 16 age 17 - 20 decline 17 - 21 , 17 - 44 . 18 related 20 decline 19 functional 20 decline 21 , 22 there 21 , 23 is 22 there 23 is 23 is 25 scarcity 24 a 25 scarcity 25 scarcity 26 of 25 scarcity 41 in 26 of 30 information 27 detailed 28 and 28 and 29 accurate 28 and 30 information 30 information 31 on 30 information 38 of 31 on 36 and 32 objectively 33 measured 33 measured 35 activity 33 measured 36 and 34 daily 35 activity 36 and 37 patterns 38 of 40 activity 39 such 40 activity 41 in 43 adults 42 older 43 adults methods : participants in the baltimore longitudinal study of aging ( n = 611 , 50 % male , mean age 67 , range 32 - 93 ) wore the actiheart portable activity monitor for 7 days in the free - living environment . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 15 , 0 ###LEFT-WALL### 44 . 1 methods 2 : 2 : 3 participants 2 : 13 = 3 participants 4 in 3 participants 9 of 4 in 8 study 5 the 8 study 6 baltimore 7 longitudinal 7 longitudinal 8 study 9 of 10 aging 11 ( 13 = 12 n 13 = 13 = 14 611 13 = 15 , 15 , 21 age 15 , 29 wore 16 50 17 % 17 % 21 age 18 male 19 , 18 male 20 mean 20 mean 21 age 21 age 22 67 21 age 24 range 21 age 29 wore 23 , 24 range 24 range 25 32 24 range 27 93 24 range 28 ) 26 - 27 93 27 93 28 ) 29 wore 34 monitor 29 wore 38 in 30 the 34 monitor 31 actiheart 34 monitor 32 portable 34 monitor 33 activity 34 monitor 34 monitor 35 for 35 for 37 days 36 7 37 days 38 in 43 environment 39 the 43 environment 40 free 41 - 40 free 43 environment 42 living 43 environment the association between activity and age was modeled using a continuous log - linear regression of activity counts on age with sex , body mass index , employment status , functional performance , and comorbid conditions as covariates . 0 ###LEFT-WALL### 2 association 0 ###LEFT-WALL### 8 modeled 0 ###LEFT-WALL### 13 - 0 ###LEFT-WALL### 39 . 1 the 2 association 2 association 3 between 2 association 7 was 3 between 5 and 4 activity 5 and 5 and 6 age 7 was 8 modeled 8 modeled 9 using 9 using 12 log 10 a 11 continuous 10 a 12 log 11 continuous 12 log 13 - 15 regression 13 - 18 counts 14 linear 15 regression 15 regression 16 of 15 regression 18 counts 16 of 17 activity 18 counts 19 on 18 counts 20 age 18 counts 21 with 18 counts 37 as 21 with 34 and 22 sex 23 , 23 , 26 index 23 , 27 , 24 body 26 index 25 mass 26 index 27 , 29 status 27 , 30 , 28 employment 29 status 30 , 32 performance 30 , 34 and 31 functional 32 performance 33 , 34 and 34 and 36 conditions 35 comorbid 36 conditions 37 as 38 covariates results : in the fully adjusted model , continuous analyses demonstrated that overall physical activity counts were 1.3 % lower for each year increase in age . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 10 analyses 2 : 11 demonstrated 2 : 27 . 3 in 7 model 3 in 8 , 3 in 10 analyses 4 the 7 model 5 fully 6 adjusted 6 adjusted 7 model 9 continuous 10 analyses 10 analyses 11 demonstrated 11 demonstrated 12 that 12 that 13 overall 12 that 16 counts 12 that 17 were 14 physical 15 activity 15 activity 16 counts 16 counts 17 were 17 were 19 % 18 1.3 19 % 19 % 20 lower 19 % 25 in 20 lower 21 for 21 for 24 increase 22 each 24 increase 23 year 24 increase 25 in 26 age although there were no differences among morning levels of activity , there was significantly lower afternoon and evening activity in older individuals ( p < [.] 01 ) . 0 ###LEFT-WALL### 12 there 0 ###LEFT-WALL### 13 was 0 ###LEFT-WALL### 29 . 1 although 2 there 1 although 3 were 1 although 11 , 1 although 12 there 2 there 3 were 3 were 5 differences 4 no 5 differences 5 differences 6 among 6 among 8 levels 7 morning 8 levels 8 levels 9 of 9 of 10 activity 12 there 13 was 13 was 14 significantly 13 was 17 and 15 lower 16 afternoon 16 afternoon 17 and 17 and 19 activity 17 and 28 ) 18 evening 19 activity 19 activity 20 in 20 in 22 individuals 21 older 22 individuals 22 individuals 25 < 23 ( 25 < 24 p 25 < 25 < 27 01 after adjusting for age , poor functional performance , nonworking status , and higher body mass index were independently associated with less physical activity ( p < [.] 001 ) . 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 20 associated 0 ###LEFT-WALL### 31 . 1 after 2 adjusting 1 after 5 , 1 after 13 and 2 adjusting 3 for 3 for 4 age 6 poor 8 performance 7 functional 8 performance 8 performance 9 , 9 , 11 status 9 , 13 and 10 nonworking 11 status 12 , 13 and 13 and 17 index 13 and 18 were 14 higher 15 body 15 body 17 index 16 mass 17 index 18 were 19 independently 18 were 20 associated 20 associated 21 with 20 associated 27 < 21 with 24 activity 22 less 24 activity 23 physical 24 activity 25 ( 27 < 26 p 27 < 27 < 29 001 27 < 30 ) conclusions : the use of accelerometers to characterize minute - by [-] minute [intensity] , cumulative physical activity counts , and daily activity patterns [provides] detailed data not gathered by traditional subjective methods , particularly at low levels of activity . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 41 . 1 conclusions 2 : 2 : 4 use 3 the 4 use 4 use 5 of 5 of 6 accelerometers 6 accelerometers 7 to 6 accelerometers 8 characterize 6 accelerometers 9 minute 7 to 8 characterize 9 minute 11 by 9 minute 35 particularly 10 - 11 by 11 by 21 and 11 by 34 , 13 minute 15 , 15 , 19 counts 15 , 21 and 16 cumulative 19 counts 17 physical 19 counts 18 activity 19 counts 20 , 21 and 21 and 27 data 21 and 34 , 22 daily 26 detailed 23 activity 26 detailed 24 patterns 26 detailed 26 detailed 27 data 27 data 28 not 27 data 30 by 28 not 29 gathered 30 by 33 methods 31 traditional 33 methods 32 subjective 33 methods 35 particularly 36 at 36 at 38 levels 37 low 38 levels 38 levels 39 of 39 of 40 activity the findings of a 1.3 % decrease per year in activity from mid - [to] [-] late life , and the corresponding drop in afternoon and evening activity , provide new information that may be useful when targeting future interventions . 0 ###LEFT-WALL### 20 and 0 ###LEFT-WALL### 29 , 0 ###LEFT-WALL### 41 . 1 the 2 findings 2 findings 3 of 2 findings 12 from 2 findings 20 and 3 of 7 decrease 4 a 7 decrease 5 1.3 6 % 6 % 7 decrease 7 decrease 8 per 7 decrease 10 in 8 per 9 year 10 in 11 activity 12 from 18 life 13 mid 14 - 13 mid 18 life 17 late 18 life 19 , 20 and 20 and 22 corresponding 20 and 29 , 21 the 22 corresponding 23 drop 24 in 23 drop 29 , 24 in 26 and 25 afternoon 26 and 26 and 28 activity 27 evening 28 activity 29 , 30 provide 29 , 37 when 30 provide 32 information 31 new 32 information 32 information 33 that 32 information 34 may 33 that 34 may 34 may 35 be 35 be 36 useful 37 when 38 targeting 38 targeting 40 interventions 39 future 40 interventions further , this methodology addresses essential gaps in understanding activity patterns and trends in more sedentary sectors of the population . 0 ###LEFT-WALL### 4 methodology 0 ###LEFT-WALL### 5 addresses 0 ###LEFT-WALL### 21 . 1 further 2 , 1 further 4 methodology 3 this 4 methodology 4 methodology 5 addresses 5 addresses 7 gaps 5 addresses 8 in 6 essential 7 gaps 8 in 9 understanding 9 understanding 10 activity 9 understanding 14 in 10 activity 12 and 11 patterns 12 and 12 and 13 trends 14 in 17 sectors 15 more 17 sectors 16 sedentary 17 sectors 17 sectors 18 of 18 of 20 population 19 the 20 population background : we addressed two understudied issues in estimating lower extremity functional trajectories in older adults - incorporating the effect of mortality and evaluating heterogeneity among african americans . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 3 we 2 : 4 addressed 3 we 4 addressed 4 addressed 7 issues 5 two 7 issues 6 understudied 7 issues 7 issues 8 in 7 issues 14 in 8 in 9 estimating 9 estimating 13 trajectories 10 lower 11 extremity 11 extremity 13 trajectories 12 functional 13 trajectories 14 in 16 adults 15 older 16 adults 16 adults 18 incorporating 17 - 18 incorporating 18 incorporating 23 and 18 incorporating 26 among 18 incorporating 29 . 19 the 23 and 20 effect 21 of 20 effect 23 and 21 of 22 mortality 23 and 25 heterogeneity 24 evaluating 25 heterogeneity 26 among 28 americans 27 african 28 americans methods : data were taken from the 998 participants in the african american health cohort . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 3 data 2 : 5 taken 2 : 16 . 3 data 4 were 4 were 5 taken 5 taken 6 from 5 taken 10 in 6 from 9 participants 7 the 8 998 8 998 9 participants 10 in 15 cohort 11 the 15 cohort 12 african 15 cohort 13 american 15 cohort 14 health 15 cohort a highly reliable [and] valid [8] - item lower extremity function scale was used at baseline and at the 1 [-] , 2 - , 3 - , 4 - , 7 - , and 9 - [year] follow - up interviews . 0 ###LEFT-WALL### 12 scale 0 ###LEFT-WALL### 14 used 0 ###LEFT-WALL### 31 , 1 a 2 highly 1 a 12 scale 2 highly 3 reliable 3 reliable 8 item 5 valid 7 - 5 valid 8 item 8 item 12 scale 9 lower 10 extremity 10 extremity 12 scale 11 function 12 scale 12 scale 13 was 13 was 14 used 14 used 17 and 15 at 16 baseline 15 at 17 and 17 and 18 at 18 at 20 1 19 the 20 1 20 1 23 2 20 1 26 3 20 1 29 4 22 , 23 2 23 2 24 - 25 , 26 3 26 3 27 - 28 , 29 4 29 4 30 - 31 , 32 7 31 , 33 - 31 , 40 - 32 7 33 - 33 - 35 and 34 , 35 and 35 and 36 9 35 and 37 - 36 9 37 - 37 - 39 follow 40 - 41 up 40 - 43 . 41 up 42 interviews semiparametric ( ie , discrete ) group - based mixture modeling identified the trajectories , and multinomial logistic regression identified risk factors for differential trajectory groups . 0 ###LEFT-WALL### 7 group 0 ###LEFT-WALL### 8 - 0 ###LEFT-WALL### 27 . 1 semiparametric 3 ie 1 semiparametric 7 group 2 ( 3 ie 3 ie 4 , 5 discrete 6 ) 5 discrete 7 group 8 - 11 modeling 8 - 12 identified 8 - 16 and 9 based 10 mixture 10 mixture 11 modeling 11 modeling 12 identified 12 identified 14 trajectories 13 the 14 trajectories 15 , 16 and 16 and 19 regression 16 and 20 identified 17 multinomial 19 regression 18 logistic 19 regression 19 regression 20 identified 20 identified 22 factors 21 risk 22 factors 22 factors 23 for 23 for 26 groups 24 differential 26 groups 25 trajectory 26 groups results : when treating mortality as informative censoring , six discrete trajectories were observed with 45 % of the participants belonging to [three] stable trajectories [(] good , fair , or poor function ) , and the remainder belonging to three declining trajectories [(] very high function with minimal improvement then minimal decline , very good function with a slow and modest decline , and very good function with a large and quick decline ) . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 9 , 1 results 2 : 2 : 3 when 3 when 4 treating 4 treating 5 mortality 4 treating 6 as 6 as 8 censoring 7 informative 8 censoring 9 , 12 trajectories 10 six 12 trajectories 11 discrete 12 trajectories 12 trajectories 13 were 13 were 14 observed 14 observed 15 with 15 with 17 % 15 with 21 belonging 16 45 17 % 17 % 18 of 18 of 20 participants 19 the 20 participants 21 belonging 22 to 22 to 24 stable 24 stable 36 and 25 trajectories 29 fair 27 good 28 , 27 good 29 fair 29 fair 31 or 30 , 31 or 31 or 33 function 31 or 34 ) 31 or 36 and 32 poor 33 function 35 , 36 and 36 and 39 belonging 36 and 40 to 37 the 39 belonging 38 remainder 39 belonging 40 to 41 three 41 three 42 declining 41 three 48 with 42 declining 47 function 43 trajectories 47 function 45 very 46 high 46 high 47 function 48 with 53 decline 49 minimal 50 improvement 50 improvement 53 decline 51 then 52 minimal 52 minimal 53 decline 53 decline 65 and 54 , 65 and 55 very 56 good 56 good 57 function 57 function 58 with 57 function 65 and 58 with 63 decline 59 a 63 decline 60 slow 61 and 61 and 62 modest 61 and 63 decline 64 , 65 and 65 and 68 function 65 and 75 ) 65 and 76 . 66 very 67 good 67 good 68 function 68 function 69 with 69 with 74 decline 70 a 74 decline 71 large 72 and 72 and 73 quick 72 and 74 decline conclusion : substantial heterogeneity in lower extremity function trajectories exists in the african american health cohort , after appropriately treating mortality as informative censoring . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 4 heterogeneity 2 : 10 exists 3 substantial 4 heterogeneity 4 heterogeneity 5 in 4 heterogeneity 10 exists 5 in 9 trajectories 6 lower 8 function 7 extremity 8 function 8 function 9 trajectories 10 exists 11 in 11 in 16 cohort 12 the 16 cohort 13 african 16 cohort 14 american 16 cohort 15 health 16 cohort 16 cohort 18 after 17 , 18 after 18 after 20 treating 18 after 25 . 19 appropriately 20 treating 20 treating 21 mortality 20 treating 22 as 22 as 24 censoring 23 informative 24 censoring one reason for the rise in the prevalence of alzheimer 's disease ( ad ) since the 1980s is the new association between the disease and aging . 0 ###LEFT-WALL### 2 reason 0 ###LEFT-WALL### 19 is 0 ###LEFT-WALL### 28 . 1 one 2 reason 2 reason 3 for 2 reason 19 is 3 for 5 rise 4 the 5 rise 5 rise 6 in 6 in 8 prevalence 7 the 8 prevalence 8 prevalence 9 of 8 prevalence 16 since 9 of 12 disease 10 alzheimer 11 's 11 's 12 disease 12 disease 14 ad 13 ( 14 ad 14 ad 15 ) 16 since 18 1980s 17 the 18 1980s 19 is 22 association 20 the 22 association 21 new 22 association 22 association 23 between 23 between 26 and 24 the 25 disease 25 disease 26 and 26 and 27 aging this paper explores the current representations of ad , questioning their relationships to aging , thanks to a literature review of 49 articles published in french and in english between 1995 and june 2010 . 0 ###LEFT-WALL### 2 paper 0 ###LEFT-WALL### 3 explores 0 ###LEFT-WALL### 35 . 1 this 2 paper 2 paper 3 explores 3 explores 6 representations 3 explores 17 to 4 the 6 representations 5 current 6 representations 6 representations 7 of 6 representations 10 questioning 7 of 8 ad 9 , 10 questioning 10 questioning 12 relationships 10 questioning 13 to 10 questioning 15 , 11 their 12 relationships 13 to 14 aging 16 thanks 17 to 17 to 20 review 18 a 19 literature 18 a 20 review 19 literature 20 review 20 review 21 of 20 review 24 published 21 of 23 articles 22 49 23 articles 24 published 27 and 25 in 26 french 25 in 27 and 27 and 28 in 28 in 32 and 29 english 30 between 29 english 32 and 30 between 31 1995 32 and 33 june 33 june 34 2010 aging appears to be a concurrent diagnosis for ad , both for the lay public and for health professionals , but this confusion , which can be interpreted as a lack of medicalization of memory loss on the conceptual level , does not necessarily constitute an obstacle to medical intervention . 0 ###LEFT-WALL### 1 aging 0 ###LEFT-WALL### 2 appears 0 ###LEFT-WALL### 24 , 0 ###LEFT-WALL### 51 . 1 aging 2 appears 2 appears 3 to 2 appears 4 be 3 to 4 be 4 be 7 diagnosis 4 be 8 for 4 be 21 but 5 a 6 concurrent 5 a 7 diagnosis 6 concurrent 7 diagnosis 8 for 9 ad 9 ad 11 both 10 , 11 both 11 both 16 and 11 both 20 , 12 for 15 public 12 for 16 and 13 the 15 public 14 lay 15 public 16 and 17 for 17 for 19 professionals 18 health 19 professionals 20 , 21 but 21 but 23 confusion 21 but 24 , 22 this 23 confusion 24 , 25 which 24 , 41 , 25 which 26 can 26 can 41 , 27 be 28 interpreted 27 be 41 , 28 interpreted 29 as 28 interpreted 37 on 29 as 31 lack 30 a 31 lack 31 lack 32 of 32 of 33 medicalization 33 medicalization 34 of 34 of 36 loss 35 memory 36 loss 37 on 40 level 38 the 40 level 39 conceptual 40 level 41 , 42 does 41 , 48 to 42 does 43 not 42 does 45 constitute 44 necessarily 45 constitute 45 constitute 47 obstacle 46 an 47 obstacle 48 to 50 intervention 49 medical 50 intervention the transformation of senile dementia into ad can diminish , as well [as] reinforce [,] stigmatization of people with ad . 0 ###LEFT-WALL### 2 transformation 0 ###LEFT-WALL### 10 , 0 ###LEFT-WALL### 21 . 1 the 2 transformation 2 transformation 3 of 2 transformation 8 can 3 of 5 dementia 4 senile 5 dementia 5 dementia 6 into 6 into 7 ad 8 can 10 , 9 diminish 10 , 10 , 14 reinforce 11 as 12 well 12 well 14 reinforce 14 reinforce 16 stigmatization 14 reinforce 19 with 16 stigmatization 17 of 17 of 18 people 19 with 20 ad moreover , elderly people with ad are subjected to both the persisting stigmas of aging and [of] dementia as well [as] , for most of them , that of feminine cognitive incompetence . 0 ###LEFT-WALL### 4 people 0 ###LEFT-WALL### 8 subjected 1 moreover 2 , 1 moreover 4 people 3 elderly 4 people 4 people 5 with 4 people 7 are 5 with 6 ad 7 are 8 subjected 8 subjected 9 to 8 subjected 19 as 8 subjected 23 for 9 to 16 and 10 both 16 and 11 the 13 stigmas 12 persisting 13 stigmas 13 stigmas 14 of 13 stigmas 16 and 14 of 15 aging 16 and 18 dementia 19 as 20 well 22 , 23 for 23 for 24 most 23 for 33 . 24 most 25 of 24 most 28 that 25 of 26 them 27 , 28 that 28 that 29 of 28 that 33 . 29 of 32 incompetence 30 feminine 32 incompetence 31 cognitive 32 incompetence researchers have explored perceptions of health care services among people with amyotrophic lateral sclerosis ( als ) , but little is known about how and why people with als engage with services . 0 ###LEFT-WALL### 1 researchers 0 ###LEFT-WALL### 3 explored 0 ###LEFT-WALL### 19 but 0 ###LEFT-WALL### 30 engage 0 ###LEFT-WALL### 33 . 1 researchers 2 have 2 have 3 explored 3 explored 4 perceptions 3 explored 9 among 3 explored 11 with 4 perceptions 5 of 5 of 8 services 6 health 7 care 7 care 8 services 9 among 10 people 11 with 14 sclerosis 12 amyotrophic 14 sclerosis 13 lateral 14 sclerosis 14 sclerosis 16 als 15 ( 16 als 16 als 17 ) 18 , 19 but 19 but 20 little 19 but 22 known 20 little 21 is 21 is 22 known 22 known 23 about 23 about 25 and 24 how 25 and 25 and 26 why 25 and 27 people 25 and 30 engage 27 people 28 with 27 people 30 engage 28 with 29 als 30 engage 31 with 31 with 32 services we undertook a grounded theory study to identify key psychosocial processes that underpin how and why people with als engage with health care services . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 undertook 0 ###LEFT-WALL### 25 . 1 we 2 undertook 2 undertook 6 study 2 undertook 7 to 2 undertook 21 with 3 a 6 study 4 grounded 6 study 5 theory 6 study 7 to 8 identify 8 identify 11 processes 9 key 11 processes 10 psychosocial 11 processes 11 processes 12 that 11 processes 13 underpin 12 that 13 underpin 13 underpin 15 and 14 how 15 and 15 and 16 why 15 and 17 people 15 and 20 engage 17 people 18 with 17 people 20 engage 18 with 19 als 21 with 24 services 22 health 24 services 23 care 24 services we conducted [in] - depth interviews with 34 participants sampled from the irish als population - based register . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 conducted 0 ###LEFT-WALL### 4 - 0 ###LEFT-WALL### 19 . 1 we 2 conducted 4 - 6 interviews 4 - 18 register 5 depth 6 interviews 6 interviews 7 with 6 interviews 10 sampled 6 interviews 18 register 7 with 9 participants 8 34 9 participants 10 sampled 11 from 10 sampled 16 - 10 sampled 17 based 11 from 15 population 12 the 15 population 13 irish 14 als 14 als 15 population we found that age and life stage shaped participants ' decision making about care . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 found 0 ###LEFT-WALL### 15 . 1 we 2 found 2 found 3 that 3 that 5 and 3 that 8 shaped 4 age 5 and 5 and 7 stage 5 and 8 shaped 6 life 7 stage 8 shaped 11 decision 8 shaped 13 about 9 participants 10 ' 10 ' 11 decision 11 decision 12 making 13 about 14 care participants in later life were more accepting of als and of death than young and middle - aged participants . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 5 were 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 20 . 1 participants 2 in 1 participants 5 were 2 in 4 life 3 later 4 life 5 were 7 accepting 6 more 7 accepting 7 accepting 8 of 8 of 9 als 10 and 15 and 10 and 18 aged 11 of 12 death 11 of 15 and 13 than 15 and 14 young 15 and 15 and 16 middle 15 and 17 - 15 and 18 aged 18 aged 19 participants family was the primary context to [how] participants engaged with services , and their decisions about care were shaped by parenthood at different life stages . 0 ###LEFT-WALL### 1 family 0 ###LEFT-WALL### 2 was 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 26 . 1 family 2 was 2 was 5 context 3 the 5 context 4 primary 5 context 5 context 6 to 5 context 9 engaged 6 to 8 participants 9 engaged 10 with 10 with 11 services 12 , 13 and 13 and 15 decisions 13 and 19 shaped 14 their 15 decisions 15 decisions 16 about 15 decisions 18 were 16 about 17 care 18 were 19 shaped 19 shaped 20 by 19 shaped 22 at 20 by 21 parenthood 22 at 25 stages 23 different 24 life 24 life 25 stages health care professionals need to be attuned to the impact of life - course trajectories and family relations on the decisions people with als make about their care . 0 ###LEFT-WALL### 3 professionals 0 ###LEFT-WALL### 4 need 1 health 2 care 2 care 3 professionals 3 professionals 4 need 4 need 5 to 4 need 7 attuned 5 to 6 be 6 be 7 attuned 7 attuned 8 to 8 to 10 impact 9 the 10 impact 10 impact 11 of 11 of 12 life 12 life 16 and 13 - 16 and 14 course 15 trajectories 15 trajectories 16 and 16 and 18 relations 16 and 19 on 16 and 22 people 16 and 25 make 16 and 29 . 17 family 18 relations 19 on 21 decisions 20 the 21 decisions 22 people 23 with 22 people 25 make 23 with 24 als 25 make 26 about 26 about 28 care 27 their 28 care this protocol measures externalization of aminophospholipids ( apls ) to the outside of the plasma membrane using mass spectrometry [(] [ms] [ )( 0 ###LEFT-WALL### 2 protocol 0 ###LEFT-WALL### 3 measures 0 ###LEFT-WALL### 23 )( 1 this 2 protocol 2 protocol 3 measures 3 measures 4 externalization 3 measures 10 to 4 externalization 5 of 5 of 6 aminophospholipids 6 aminophospholipids 8 apls 7 ( 8 apls 8 apls 9 ) 10 to 12 outside 11 the 12 outside 12 outside 13 of 13 of 16 membrane 14 the 16 membrane 15 plasma 16 membrane 16 membrane 17 using 17 using 19 spectrometry 18 mass 19 spectrometry apl externalization occurs in numerous events , and it is relevant for transplant medicine , immunity and cancer . 0 ###LEFT-WALL### 2 externalization 0 ###LEFT-WALL### 3 occurs 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 19 . 1 apl 2 externalization 2 externalization 3 occurs 3 occurs 4 in 4 in 6 events 5 numerous 6 events 7 , 8 and 8 and 9 it 8 and 10 is 9 it 10 is 10 is 11 relevant 11 relevant 12 for 12 for 17 and 13 transplant 14 medicine 14 medicine 15 , 15 , 16 immunity 15 , 17 and 17 and 18 cancer in [this] protocol , externalized apls are chemically modified by using a cell - impermeable reagent ( sulfo - nhs - biotin ) , and then they are isolated via a liquid:liquid extraction and quantified by reverse [-] phase liquid chromatography tandem ms ( lc - ms/ms ) [against] [in] - house - generated standards . 0 ###LEFT-WALL### 3 protocol 0 ###LEFT-WALL### 4 , 1 in 3 protocol 4 , 6 apls 4 , 14 - 5 externalized 6 apls 6 apls 7 are 7 are 8 chemically 7 are 9 modified 9 modified 10 by 10 by 11 using 11 using 13 cell 12 a 13 cell 14 - 16 reagent 14 - 25 and 15 impermeable 16 reagent 16 reagent 18 sulfo 16 reagent 20 nhs 17 ( 18 sulfo 18 sulfo 19 - 19 - 20 nhs 20 nhs 22 biotin 20 nhs 24 , 21 - 22 biotin 22 biotin 23 ) 25 and 27 they 25 and 34 and 26 then 27 they 27 they 28 are 28 are 34 and 29 isolated 30 via 29 isolated 33 extraction 29 isolated 34 and 30 via 32 liquid:liquid 31 a 32 liquid:liquid 34 and 35 quantified 35 quantified 36 by 35 quantified 45 lc 36 by 42 tandem 37 reverse 40 liquid 39 phase 40 liquid 40 liquid 42 tandem 41 chromatography 42 tandem 43 ms 45 lc 44 ( 45 lc 45 lc 46 - 45 lc 47 ms/ms 45 lc 52 house 46 - 47 ms/ms 47 ms/ms 48 ) 51 - 52 house 52 house 55 standards 52 house 56 . 53 - 55 standards 54 generated 55 standards 55 standards 56 . this protocol describes a complementary method to existing assays that are not quantitative ( e.g [.] , annexin v flow cytometry [ )(, and [it] [is] applicable to the study of membrane reorganization in all cell types during apoptosis ( e.g [.] , during development , cancer , psychiatric disorders and other conditions , aging , vesiculation and cell division ) . 0 ###LEFT-WALL### 2 protocol 0 ###LEFT-WALL### 3 describes 1 this 2 protocol 2 protocol 3 describes 3 describes 6 method 4 a 6 method 5 complementary 6 method 6 method 7 to 7 to 9 assays 8 existing 9 assays 9 assays 10 that 9 assays 11 are 10 that 11 are 11 are 12 not 11 are 20 flow 13 quantitative 15 e.g 13 quantitative 18 annexin 14 ( 15 e.g 15 e.g 17 , 18 annexin 19 v 18 annexin 20 flow 20 flow 24 and 20 flow 31 of 21 cytometry 24 and 23 )(, 24 and 24 and 27 applicable 27 applicable 28 to 28 to 30 study 29 the 30 study 31 of 33 reorganization 32 membrane 33 reorganization 33 reorganization 34 in 33 reorganization 36 cell 33 reorganization 37 types 34 in 35 all 36 cell 37 types 37 types 38 during 37 types 44 during 38 during 39 apoptosis 39 apoptosis 41 e.g 40 ( 41 e.g 41 e.g 43 , 44 during 51 and 45 development 46 , 46 , 47 cancer 46 , 48 , 48 , 50 disorders 48 , 51 and 49 psychiatric 50 disorders 51 and 53 conditions 51 and 54 , 51 and 55 aging 51 and 58 and 52 other 53 conditions 56 , 58 and 57 vesiculation 58 and 58 and 60 division 58 and 61 ) 58 and 62 . 59 cell 60 division the protocol takes ∼2 - 4 d , including the generation of standards . 0 ###LEFT-WALL### 2 protocol 0 ###LEFT-WALL### 3 takes 1 the 2 protocol 2 protocol 3 takes 3 takes 4 ∼2 4 ∼2 7 d 4 ∼2 9 including 5 - 7 d 6 4 7 d 7 d 8 , 8 , 9 including 9 including 11 generation 9 including 14 . 10 the 11 generation 11 generation 12 of 12 of 13 standards background : lifetime risk estimation is used to predict long - term cardiovascular disease ( cvd ) risk across the entire life span . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 11 - 1 background 2 : 2 : 4 risk 3 lifetime 4 risk 4 risk 5 estimation 4 risk 9 predict 5 estimation 6 is 6 is 7 used 7 used 8 to 7 used 9 predict 8 to 9 predict 9 predict 10 long 11 - 12 term 11 - 24 . 12 term 14 disease 12 term 18 risk 12 term 19 across 13 cardiovascular 14 disease 14 disease 16 cvd 15 ( 16 cvd 16 cvd 17 ) 19 across 23 span 20 the 23 span 21 entire 22 life 22 life 23 span however , most of the lifetime risk estimation came from the studies based on western population . 0 ###LEFT-WALL### 8 estimation 0 ###LEFT-WALL### 9 came 0 ###LEFT-WALL### 17 . 1 however 2 , 1 however 8 estimation 3 most 4 of 3 most 8 estimation 4 of 8 estimation 5 the 8 estimation 6 lifetime 8 estimation 7 risk 8 estimation 8 estimation 9 came 9 came 10 from 10 from 12 studies 11 the 12 studies 12 studies 13 based 13 based 14 on 14 on 16 population 15 western 16 population this study aimed to assess the lifetime risk of cvd and the impact of risk factors on lifetime risk of cvd in chinese population . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 aimed 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 25 . 1 this 2 study 2 study 3 aimed 3 aimed 4 to 3 aimed 5 assess 4 to 5 assess 5 assess 8 risk 6 the 8 risk 7 lifetime 8 risk 8 risk 9 of 9 of 10 cvd 11 and 13 impact 11 and 16 factors 12 the 13 impact 13 impact 14 of 13 impact 16 factors 14 of 15 risk 16 factors 17 on 16 factors 19 risk 18 lifetime 19 risk 19 risk 20 of 20 of 21 cvd 21 cvd 22 in 22 in 24 population 23 chinese 24 population design : prospective population - based cohort study . 0 ###LEFT-WALL### 1 design 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 5 - 0 ###LEFT-WALL### 9 . 1 design 2 : 2 : 4 population 3 prospective 4 population 5 - 8 study 6 based 7 cohort 7 cohort 8 study methods : the study sample came from the chinese multi - provincial cohort study ( cmcs ) , 21,953 participants aged 35 to 84 years without cvd at the baseline were included . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 33 . 2 : 5 sample 2 : 6 came 2 : 18 , 3 the 5 sample 4 study 5 sample 5 sample 6 came 6 came 7 from 7 from 10 multi 8 the 10 multi 9 chinese 10 multi 10 multi 16 cmcs 11 - 16 cmcs 12 provincial 16 cmcs 13 cohort 14 study 14 study 16 cmcs 15 ( 16 cmcs 16 cmcs 17 ) 16 cmcs 18 , 18 , 20 participants 18 , 21 aged 19 21,953 20 participants 20 participants 21 aged 21 aged 23 to 22 35 23 to 23 to 24 84 24 84 25 years 25 years 26 without 25 years 31 were 26 without 27 cvd 27 cvd 28 at 28 at 30 baseline 29 the 30 baseline 31 were 32 included the modified kaplan - meier method was used to calculate the lifetime risk of cvd . 0 ###LEFT-WALL### 3 kaplan 0 ###LEFT-WALL### 4 - 0 ###LEFT-WALL### 16 . 1 the 3 kaplan 2 modified 3 kaplan 4 - 5 meier 5 meier 6 method 5 meier 10 calculate 6 method 7 was 7 was 8 used 8 used 9 to 8 used 10 calculate 9 to 10 calculate 10 calculate 13 risk 11 the 13 risk 12 lifetime 13 risk 13 risk 14 of 14 of 15 cvd results and conclusions : during follow - up years from 1992 to 2010 , 1,280 participants developed acute cvd events and 1,401 died . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 6 follow 0 ###LEFT-WALL### 14 , 0 ###LEFT-WALL### 24 . 1 results 3 conclusions 1 results 5 during 1 results 6 follow 2 and 3 conclusions 3 conclusions 4 : 4 : 5 during 6 follow 8 up 7 - 8 up 8 up 9 years 8 up 14 , 9 years 12 to 10 from 12 to 11 1992 12 to 12 to 13 2010 14 , 16 participants 14 , 17 developed 14 , 21 and 15 1,280 16 participants 16 participants 17 developed 17 developed 20 events 18 acute 20 events 19 cvd 20 events 21 and 22 1,401 21 and 23 died 22 1,401 23 died the lifetime cvd risk , up to age 80 for men and women at age 35 , were 24.4 [%] and 20.2 % respectively . 0 ###LEFT-WALL### 4 risk 0 ###LEFT-WALL### 18 were 0 ###LEFT-WALL### 25 . 1 the 4 risk 2 lifetime 4 risk 3 cvd 4 risk 4 risk 6 up 4 risk 18 were 5 , 6 up 6 up 7 to 6 up 14 at 6 up 17 , 7 to 8 age 8 age 9 80 8 age 10 for 10 for 12 and 11 men 12 and 12 and 13 women 14 at 15 age 15 age 16 35 18 were 23 % 18 were 24 respectively 19 24.4 21 and 21 and 22 20.2 21 and 23 % a very low lifetime risk was found in individuals with an optimal profile of risk factors which modified the effect of aging . 0 ###LEFT-WALL### 5 risk 0 ###LEFT-WALL### 7 found 0 ###LEFT-WALL### 23 . 1 a 5 risk 2 very 3 low 3 low 4 lifetime 4 lifetime 5 risk 5 risk 6 was 6 was 7 found 7 found 8 in 7 found 10 with 8 in 9 individuals 10 with 13 profile 11 an 13 profile 12 optimal 13 profile 13 profile 14 of 13 profile 21 of 14 of 16 factors 15 risk 16 factors 16 factors 17 which 16 factors 18 modified 17 which 18 modified 18 modified 20 effect 19 the 20 effect 21 of 22 aging by contrast [,] with two or more high risk factors the lifetime risk up to age 80 reached 51.1 % for men and 38.6 % [for] women at age 35 . 0 ###LEFT-WALL### 13 risk 0 ###LEFT-WALL### 18 reached 0 ###LEFT-WALL### 31 . 1 by 6 or 1 by 13 risk 2 contrast 4 with 2 contrast 6 or 4 with 5 two 6 or 10 factors 7 more 10 factors 8 high 10 factors 9 risk 10 factors 11 the 13 risk 12 lifetime 13 risk 13 risk 14 up 13 risk 18 reached 14 up 15 to 15 to 16 age 16 age 17 80 18 reached 20 % 18 reached 21 for 18 reached 28 at 19 51.1 20 % 21 for 23 and 22 men 23 and 23 and 27 women 24 38.6 27 women 25 % 27 women 28 at 29 age 29 age 30 35 the integrated status of major cvd risk factors can determine lifetime cardiovascular health and cvd risk in chinese . 0 ###LEFT-WALL### 3 status 0 ###LEFT-WALL### 10 determine 0 ###LEFT-WALL### 19 . 1 the 3 status 2 integrated 3 status 3 status 4 of 3 status 9 can 4 of 8 factors 5 major 8 factors 6 cvd 8 factors 7 risk 8 factors 9 can 10 determine 10 determine 16 risk 10 determine 17 in 11 lifetime 16 risk 12 cardiovascular 13 health 13 health 14 and 14 and 15 cvd 14 and 16 risk 17 in 18 chinese early prevention with a goal of all risk factors at optimal levels should become the priority of cvd prevention in the future . 0 ###LEFT-WALL### 2 prevention 0 ###LEFT-WALL### 14 become 0 ###LEFT-WALL### 23 . 1 early 2 prevention 2 prevention 3 with 2 prevention 13 should 3 with 5 goal 4 a 5 goal 5 goal 6 of 6 of 9 factors 7 all 9 factors 8 risk 9 factors 9 factors 10 at 10 at 12 levels 11 optimal 12 levels 13 should 14 become 14 become 16 priority 14 become 20 in 15 the 16 priority 16 priority 17 of 17 of 19 prevention 18 cvd 19 prevention 20 in 22 future 21 the 22 future objective : identifying positive psychological factors that reduce health care use may lead to innovative efforts that help build [a] more sustainable and high - quality health care system . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 30 . 2 : 3 identifying 2 : 13 lead 2 : 25 - 3 identifying 6 factors 3 identifying 12 may 4 positive 6 factors 5 psychological 6 factors 6 factors 7 that 6 factors 8 reduce 7 that 8 reduce 8 reduce 11 use 9 health 11 use 10 care 11 use 12 may 13 lead 13 lead 14 to 13 lead 21 more 13 lead 23 and 14 to 16 efforts 15 innovative 16 efforts 16 efforts 17 that 16 efforts 18 help 17 that 18 help 18 help 19 build 22 sustainable 23 and 23 and 24 high 25 - 29 system 26 quality 28 care 27 health 28 care 28 care 29 system prospective studies indicate that life satisfaction is associated with good health behaviors , enhanced health , and longer life , but little information about the association between life satisfaction and health care use is available . 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 21 but 0 ###LEFT-WALL### 36 . 1 prospective 8 associated 1 prospective 9 with 1 prospective 17 and 2 studies 3 indicate 3 indicate 4 that 4 that 6 satisfaction 4 that 8 associated 5 life 6 satisfaction 6 satisfaction 7 is 7 is 8 associated 9 with 12 behaviors 10 good 12 behaviors 11 health 12 behaviors 12 behaviors 15 health 13 , 15 health 14 enhanced 15 health 15 health 16 , 17 and 19 life 18 longer 19 life 20 , 21 but 21 but 23 information 21 but 34 is 22 little 23 information 23 information 24 about 23 information 27 between 23 information 34 is 24 about 26 association 25 the 26 association 27 between 28 life 28 life 30 and 28 life 33 use 29 satisfaction 30 and 30 and 32 care 30 and 33 use 31 health 32 care 34 is 35 available we tested whether higher life satisfaction was prospectively associated with fewer doctor visits . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 tested 0 ###LEFT-WALL### 14 . 1 we 2 tested 2 tested 3 whether 3 whether 6 satisfaction 3 whether 9 associated 4 higher 5 life 5 life 6 satisfaction 6 satisfaction 7 was 7 was 9 associated 8 prospectively 9 associated 9 associated 10 with 10 with 13 visits 11 fewer 13 visits 12 doctor 13 visits we also examined potential interactions between life satisfaction and health behaviors . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 examined 0 ###LEFT-WALL### 12 . 1 we 3 examined 2 also 3 examined 3 examined 5 interactions 3 examined 6 between 4 potential 5 interactions 6 between 9 and 7 life 8 satisfaction 8 satisfaction 9 and 9 and 11 behaviors 10 health 11 behaviors methods : participants were 6379 adults from the health and retirement study , a prospective and nationally representative panel study of american adults older than 50 years . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 28 . 2 : 3 participants 2 : 4 were 3 participants 4 were 4 were 6 adults 4 were 20 study 5 6379 6 adults 6 adults 7 from 7 from 10 and 8 the 9 health 9 health 10 and 10 and 12 study 10 and 13 , 11 retirement 12 study 14 a 20 study 15 prospective 16 and 16 and 18 representative 16 and 19 panel 17 nationally 18 representative 19 panel 20 study 20 study 21 of 21 of 23 adults 22 american 23 adults 23 adults 24 older 24 older 25 than 25 than 27 years 26 50 27 years participants were tracked for 4 years . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 3 tracked 0 ###LEFT-WALL### 7 . 1 participants 2 were 2 were 3 tracked 3 tracked 4 for 4 for 6 years 5 4 6 years we analyzed the data using a generalized linear model with a gamma distribution and log link . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 analyzed 0 ###LEFT-WALL### 17 . 1 we 2 analyzed 2 analyzed 4 data 2 analyzed 5 using 3 the 4 data 5 using 9 model 5 using 10 with 6 a 9 model 7 generalized 9 model 8 linear 9 model 10 with 14 and 11 a 12 gamma 11 a 13 distribution 12 gamma 13 distribution 13 distribution 14 and 14 and 16 link 15 log 16 link results : higher life satisfaction was associated with fewer doctor visits . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 5 satisfaction 2 : 7 associated 2 : 12 . 3 higher 4 life 4 life 5 satisfaction 5 satisfaction 6 was 6 was 7 associated 7 associated 8 with 8 with 11 visits 9 fewer 11 visits 10 doctor 11 visits on a 6 [-] point life satisfaction scale , each unit increase in life satisfaction was associated with an 11 % decrease in doctor visits -- after adjusting for sociodemographic factors [(] relative risk = 0.89 , 95 % confidence interval = 0.86 - 0.93 ) . 0 ###LEFT-WALL### 34 risk 0 ###LEFT-WALL### 35 = 0 ###LEFT-WALL### 47 . 1 on 8 scale 1 on 26 -- 1 on 34 risk 2 a 8 scale 3 6 5 point 5 point 6 life 6 life 8 scale 7 satisfaction 8 scale 8 scale 12 increase 9 , 12 increase 10 each 12 increase 11 unit 12 increase 12 increase 13 in 12 increase 18 with 12 increase 26 -- 13 in 14 life 14 life 15 satisfaction 14 life 16 was 14 life 17 associated 15 satisfaction 16 was 18 with 22 decrease 19 an 22 decrease 20 11 21 % 21 % 22 decrease 22 decrease 23 in 23 in 25 visits 24 doctor 25 visits 27 after 28 adjusting 27 after 34 risk 28 adjusting 29 for 29 for 31 factors 30 sociodemographic 31 factors 33 relative 34 risk 34 risk 35 = 35 = 36 0.89 36 0.89 41 interval 37 , 41 interval 38 95 39 % 39 % 41 interval 40 confidence 41 interval 41 interval 44 - 41 interval 46 ) 42 = 43 0.86 43 0.86 44 - 44 - 45 0.93 the most satisfied respondents ( n = 1121 ; 17.58 % [ )(made 44 % fewer doctor visits than did the least satisfied ( n = 182 ; 2.85 [%] [ )( 0 ###LEFT-WALL### 2 most 0 ###LEFT-WALL### 3 satisfied 0 ###LEFT-WALL### 9 ; 0 ###LEFT-WALL### 32 )( 1 the 2 most 2 most 3 satisfied 3 satisfied 4 respondents 4 respondents 7 = 5 ( 7 = 6 n 7 = 7 = 8 1121 7 = 9 ; 9 ; 11 % 9 ; 13 )(made 9 ; 28 ; 10 17.58 11 % 11 % 13 )(made 13 )(made 15 % 13 )(made 23 satisfied 14 44 15 % 15 % 18 visits 15 % 20 did 16 fewer 18 visits 17 doctor 18 visits 18 visits 20 did 19 than 20 did 20 did 22 least 21 the 22 least 23 satisfied 26 = 24 ( 26 = 25 n 26 = 26 = 27 182 28 ; 29 2.85 the association between higher life satisfaction and reduced doctor visits remained even after adjusting for baseline health and a wide range of sociodemographic , psychosocial , and health - related covariates [(] relative risk = 0.96 , 95 % confidence interval = 0.93 - 0.99 ) . 0 ###LEFT-WALL### 7 and 0 ###LEFT-WALL### 18 and 0 ###LEFT-WALL### 47 . 1 the 2 association 2 association 3 between 2 association 7 and 3 between 6 satisfaction 4 higher 6 satisfaction 5 life 6 satisfaction 7 and 9 doctor 7 and 10 visits 7 and 14 adjusting 8 reduced 9 doctor 10 visits 11 remained 11 remained 12 even 12 even 13 after 13 after 14 adjusting 14 adjusting 15 for 15 for 17 health 16 baseline 17 health 18 and 34 risk 18 and 35 = 19 a 20 wide 19 a 34 risk 20 wide 21 range 21 range 22 of 21 range 30 related 22 of 27 and 23 sociodemographic 24 , 24 , 25 psychosocial 24 , 27 and 26 , 27 and 27 and 28 health 27 and 29 - 30 related 31 covariates 33 relative 34 risk 34 risk 35 = 35 = 36 0.96 36 0.96 41 interval 37 , 41 interval 38 95 41 interval 39 % 40 confidence 40 confidence 41 interval 41 interval 44 - 41 interval 46 ) 42 = 43 0.93 43 0.93 44 - 44 - 45 0.99 conclusions : higher life satisfaction is associated with fewer doctor visits , which may have important implications for reducing health care costs . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 22 costs 0 ###LEFT-WALL### 23 . 2 : 5 satisfaction 2 : 7 associated 2 : 12 , 3 higher 4 life 4 life 5 satisfaction 5 satisfaction 6 is 6 is 7 associated 7 associated 8 with 8 with 9 fewer 8 with 11 visits 10 doctor 11 visits 12 , 13 which 12 , 15 have 13 which 14 may 14 may 15 have 15 have 17 implications 16 important 17 implications 17 implications 18 for 18 for 19 reducing 19 reducing 20 health 20 health 21 care 20 health 22 costs 21 care 22 costs objective : the aim of the study was to investigate the relationship between supportive services provided under title iii - [b] of the older americans act ( oaa ) and the prevalence of low - care residents in nursing homes ( nhs ) . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 10 investigate 0 ###LEFT-WALL### 44 . 2 : 4 aim 2 : 8 was 3 the 4 aim 4 aim 5 of 4 aim 8 was 5 of 7 study 6 the 7 study 8 was 9 to 9 to 10 investigate 10 investigate 12 relationship 10 investigate 13 between 10 investigate 17 under 11 the 12 relationship 13 between 15 services 14 supportive 15 services 15 services 16 provided 17 under 18 title 18 title 19 iii 18 title 22 of 20 - 22 of 22 of 30 and 22 of 43 ) 23 the 25 americans 24 older 25 americans 25 americans 28 oaa 26 act 28 oaa 27 ( 28 oaa 28 oaa 29 ) 28 oaa 30 and 30 and 32 prevalence 30 and 33 of 31 the 32 prevalence 33 of 37 residents 34 low 35 - 34 low 36 care 36 care 37 residents 37 residents 38 in 38 in 39 nursing 39 nursing 40 homes 40 homes 42 nhs 41 ( 42 nhs 42 nhs 43 ) method : state program reports [(] state - level expenditure and utilization data for each oaa service ) and nh facility - level data were analyzed using a two [-] way fixed effects model . 0 ###LEFT-WALL### 1 method 0 ###LEFT-WALL### 7 state 1 method 2 : 2 : 3 state 3 state 5 reports 3 state 7 state 4 program 5 reports 5 reports 7 state 7 state 22 - 7 state 35 . 8 - 22 - 9 level 10 expenditure 10 expenditure 11 and 11 and 13 data 11 and 18 ) 11 and 19 and 12 utilization 13 data 13 data 14 for 14 for 17 service 15 each 17 service 16 oaa 17 service 19 and 21 facility 19 and 22 - 20 nh 21 facility 22 - 23 level 22 - 35 . 23 level 24 data 23 level 34 model 24 data 25 were 25 were 27 using 25 were 31 way 26 analyzed 27 using 28 a 31 way 29 two 31 way 31 way 32 fixed 31 way 33 effects 31 way 34 model 33 effects 34 model results : results suggest that every [additional] 1 % of the population age 65+ that receives personal care services is associated with a 0.8 % decrease in the proportion of low - care residents in nhs . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 4 suggest 2 : 37 . 3 results 4 suggest 4 suggest 5 that 5 that 9 % 5 that 21 associated 6 every 8 1 8 1 9 % 9 % 10 of 9 % 20 is 10 of 14 65+ 11 the 14 65+ 12 population 13 age 13 age 14 65+ 14 65+ 15 that 14 65+ 16 receives 15 that 16 receives 16 receives 19 services 17 personal 18 care 18 care 19 services 20 is 21 associated 21 associated 22 with 21 associated 27 in 22 with 26 decrease 23 a 26 decrease 24 0.8 25 % 25 % 26 decrease 27 in 29 proportion 28 the 29 proportion 29 proportion 30 of 30 of 34 residents 31 low 32 - 31 low 33 care 33 care 34 residents 34 residents 35 in 35 in 36 nhs discussion : despite efforts to rebalance long - term care , there are still many nh residents who have the functional capacity to live in a less restrictive environment . 0 ###LEFT-WALL### 1 discussion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 30 . 2 : 12 there 2 : 13 are 3 despite 4 efforts 3 despite 12 there 4 efforts 5 to 4 efforts 6 rebalance 4 efforts 10 care 5 to 6 rebalance 6 rebalance 7 long 8 - 10 care 9 term 10 care 10 care 11 , 12 there 13 are 13 are 17 residents 14 still 17 residents 15 many 16 nh 16 nh 17 residents 17 residents 18 who 17 residents 19 have 18 who 19 have 19 have 22 capacity 20 the 22 capacity 21 functional 22 capacity 22 capacity 23 to 22 capacity 24 live 23 to 24 live 24 live 25 in 25 in 29 environment 26 a 29 environment 27 less 28 restrictive 28 restrictive 29 environment this is among the first studies to suggest that states that have invested in their [in] [-] home supportive services , particularly personal care services provided through the oaa , have proportionally [fewer] of these people . 0 ###LEFT-WALL### 1 this 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 37 . 1 this 2 is 2 is 3 among 3 among 5 first 4 the 5 first 5 first 6 studies 5 first 13 invested 6 studies 7 to 6 studies 10 states 6 studies 12 have 7 to 8 suggest 8 suggest 9 that 8 suggest 10 states 9 that 10 states 10 states 11 that 12 have 13 invested 13 invested 14 in 14 in 18 home 15 their 18 home 18 home 20 services 18 home 31 have 18 home 34 of 19 supportive 20 services 20 services 25 services 20 services 31 have 21 , 25 services 22 particularly 23 personal 23 personal 24 care 24 care 25 services 25 services 26 provided 25 services 27 through 25 services 30 , 27 through 29 oaa 28 the 29 oaa 31 have 32 proportionally 34 of 36 people 35 these 36 people objective : the aim of this study was to examine disability trends among men and women aged 70+ in beijing , china ; determine whether trends are impacted [upon] by changes in population composition ; [and] investigate whether trends are experienced similarly across socio - demographic subgroups . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 48 . 2 : 4 aim 2 : 23 ; 3 the 4 aim 4 aim 5 of 4 aim 17 aged 5 of 6 this 7 study 8 was 8 was 9 to 8 was 10 examine 9 to 10 examine 10 examine 15 and 10 examine 17 aged 11 disability 12 trends 12 trends 13 among 12 trends 15 and 13 among 14 men 15 and 16 women 15 and 17 aged 17 aged 18 70+ 17 aged 23 ; 18 70+ 19 in 18 70+ 22 china 19 in 20 beijing 21 , 22 china 22 china 23 ; 23 ; 24 determine 23 ; 35 ; 24 determine 25 whether 24 determine 32 in 25 whether 26 trends 25 whether 28 impacted 26 trends 27 are 27 are 28 impacted 28 impacted 30 by 30 by 31 changes 32 in 34 composition 33 population 34 composition 35 ; 37 investigate 37 investigate 38 whether 37 investigate 43 across 38 whether 39 trends 38 whether 41 experienced 39 trends 40 are 40 are 41 experienced 41 experienced 42 similarly 43 across 47 subgroups 44 socio 45 - 44 socio 47 subgroups 46 demographic 47 subgroups method : fifteen - year panel data were used to model probability of reporting activities of daily [living] ( adls ) disability adjusting for age , sex , marital status , residence , and education . 0 ###LEFT-WALL### 1 method 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 4 - 0 ###LEFT-WALL### 36 . 1 method 2 : 2 : 3 fifteen 4 - 7 data 4 - 9 used 5 year 7 data 6 panel 7 data 7 data 8 were 8 were 9 used 9 used 10 to 9 used 24 for 10 to 11 model 11 model 12 probability 12 probability 13 of 12 probability 16 of 13 of 15 activities 14 reporting 15 activities 16 of 22 disability 17 daily 20 adls 17 daily 21 ) 17 daily 22 disability 19 ( 20 adls 20 adls 21 ) 22 disability 23 adjusting 24 for 34 and 25 age 26 , 26 , 27 sex 26 , 28 , 28 , 30 status 28 , 31 , 29 marital 30 status 31 , 32 residence 31 , 34 and 33 , 34 and 34 and 35 education predicted probabilities and average annual percent change in probabilities are reported . 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 11 reported 0 ###LEFT-WALL### 12 . 1 predicted 2 probabilities 2 probabilities 3 and 3 and 7 change 3 and 8 in 3 and 10 are 4 average 7 change 5 annual 7 change 6 percent 7 change 8 in 9 probabilities 10 are 11 reported results : the results showed increasing disability trends experienced by men , and stable or decreasing trends by women . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 20 . 2 : 4 results 2 : 5 showed 3 the 4 results 4 results 5 showed 5 showed 7 disability 5 showed 8 trends 6 increasing 7 disability 8 trends 9 experienced 8 trends 10 by 10 by 15 or 11 men 13 and 12 , 13 and 13 and 14 stable 13 and 15 or 15 or 17 trends 15 or 18 by 16 decreasing 17 trends 18 by 19 women trends would be less favorable [had] education of older population not increased over time . 0 ###LEFT-WALL### 1 trends 0 ###LEFT-WALL### 3 be 0 ###LEFT-WALL### 15 . 1 trends 2 would 2 would 3 be 3 be 7 education 4 less 5 favorable 5 favorable 7 education 7 education 8 of 8 of 10 population 9 older 10 population 10 population 11 not 11 not 12 increased 12 increased 13 over 13 over 14 time trends are much worse when bathing is excluded as an adls item . 0 ###LEFT-WALL### 1 trends 0 ###LEFT-WALL### 2 are 0 ###LEFT-WALL### 13 . 1 trends 2 are 2 are 4 worse 3 much 4 worse 4 worse 5 when 5 when 6 bathing 5 when 8 excluded 6 bathing 7 is 7 is 8 excluded 8 excluded 9 as 9 as 12 item 10 an 12 item 11 adls 12 item this is because trends in bathing were favorable whereas trends in other activities were not . 0 ###LEFT-WALL### 1 this 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 16 . 1 this 2 is 2 is 3 because 3 because 4 trends 3 because 7 were 4 trends 5 in 4 trends 7 were 5 in 6 bathing 7 were 8 favorable 8 favorable 9 whereas 9 whereas 10 trends 9 whereas 14 were 10 trends 11 in 10 trends 14 were 11 in 13 activities 12 other 13 activities 14 were 15 not discussion : on balance , results are not overly encouraging for reductions in population - level disability given population aging and increasing life expectancy in china . 0 ###LEFT-WALL### 1 discussion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 15 - 1 discussion 2 : 2 : 3 on 3 on 4 balance 4 balance 10 encouraging 5 , 10 encouraging 6 results 7 are 7 are 8 not 8 not 9 overly 9 overly 10 encouraging 10 encouraging 11 for 10 encouraging 13 in 10 encouraging 15 - 11 for 12 reductions 13 in 14 population 15 - 21 and 15 - 27 . 16 level 17 disability 17 disability 18 given 17 disability 21 and 18 given 19 population 19 population 20 aging 21 and 24 expectancy 21 and 25 in 22 increasing 23 life 23 life 24 expectancy 25 in 26 china but , future increasing education could mitigate some increases in disability rates . 0 ###LEFT-WALL### 1 but 0 ###LEFT-WALL### 13 . 1 but 2 , 1 but 5 education 1 but 7 mitigate 3 future 4 increasing 4 increasing 5 education 5 education 6 could 6 could 7 mitigate 7 mitigate 9 increases 7 mitigate 10 in 8 some 9 increases 10 in 12 rates 11 disability 12 rates genome - wide association studies ( gwas ) have identified several risk variants for late - onset alzheimer 's disease ( load ) . 0 ###LEFT-WALL### 5 studies 0 ###LEFT-WALL### 10 identified 0 ###LEFT-WALL### 24 . 1 genome 2 - 1 genome 5 studies 3 wide 4 association 4 association 5 studies 5 studies 7 gwas 5 studies 9 have 6 ( 7 gwas 7 gwas 8 ) 9 have 10 identified 10 identified 13 variants 11 several 13 variants 12 risk 13 variants 13 variants 14 for 14 for 20 disease 15 late 16 - 15 late 17 onset 17 onset 18 alzheimer 18 alzheimer 19 's 19 's 20 disease 20 disease 22 load 21 ( 22 load 22 load 23 ) these common variants have replicable but small effects on load risk and generally do not have obvious functional effects . 0 ###LEFT-WALL### 3 variants 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 20 . 1 these 3 variants 2 common 3 variants 3 variants 12 and 4 have 8 effects 4 have 9 on 4 have 12 and 5 replicable 6 but 6 but 7 small 6 but 8 effects 9 on 11 risk 10 load 11 risk 12 and 14 do 13 generally 14 do 14 do 15 not 14 do 16 have 16 have 19 effects 17 obvious 19 effects 18 functional 19 effects low - frequency coding variants , not detected by gwas , are predicted to include functional variants with larger effects on risk . 0 ###LEFT-WALL### 5 variants 0 ###LEFT-WALL### 13 predicted 0 ###LEFT-WALL### 23 . 1 low 2 - 1 low 3 frequency 3 frequency 5 variants 4 coding 5 variants 5 variants 8 detected 5 variants 12 are 6 , 7 not 6 , 8 detected 8 detected 9 by 8 detected 11 , 9 by 10 gwas 12 are 13 predicted 13 predicted 14 to 13 predicted 18 with 14 to 15 include 15 include 17 variants 16 functional 17 variants 18 with 20 effects 19 larger 20 effects 20 effects 21 on 21 on 22 risk to identify low - frequency coding variants with large effects on load risk , we carried out whole - exome sequencing ( wes ) in 14 large load families and follow - up analyses of the candidate variants in several large load case - control data sets . 0 ###LEFT-WALL### 1 to 0 ###LEFT-WALL### 2 identify 0 ###LEFT-WALL### 14 , 0 ###LEFT-WALL### 48 . 1 to 2 identify 2 identify 7 variants 2 identify 8 with 3 low 4 - 3 low 7 variants 5 frequency 6 coding 6 coding 7 variants 8 with 10 effects 9 large 10 effects 10 effects 11 on 11 on 13 risk 12 load 13 risk 14 , 15 we 14 , 30 and 14 , 32 - 15 we 30 and 16 carried 21 sequencing 16 carried 25 in 16 carried 30 and 17 out 20 exome 18 whole 19 - 18 whole 20 exome 20 exome 21 sequencing 21 sequencing 23 wes 22 ( 23 wes 23 wes 24 ) 25 in 29 families 26 14 29 families 27 large 29 families 28 load 29 families 30 and 31 follow 32 - 33 up 32 - 44 - 33 up 34 analyses 34 analyses 35 of 35 of 37 candidate 36 the 37 candidate 37 candidate 38 variants 37 candidate 43 case 38 variants 39 in 38 variants 43 case 39 in 42 load 40 several 42 load 41 large 42 load 44 - 46 data 44 - 47 sets 45 control 46 data 46 data 47 sets a rare variant in pld3 ( phospholipase d3 [;] val232met ) segregated with disease status in two independent families and doubled risk for alzheimer 's disease in seven independent case - control series with a total of more than 11,000 cases and controls of european descent . 0 ###LEFT-WALL### 30 case 0 ###LEFT-WALL### 31 - 0 ###LEFT-WALL### 47 . 1 a 2 rare 1 a 3 variant 2 rare 3 variant 3 variant 4 in 3 variant 12 segregated 3 variant 13 with 3 variant 20 and 4 in 5 pld3 5 pld3 10 val232met 6 ( 10 val232met 7 phospholipase 10 val232met 8 d3 10 val232met 10 val232met 11 ) 13 with 15 status 14 disease 15 status 15 status 16 in 16 in 19 families 17 two 19 families 18 independent 19 families 20 and 22 risk 20 and 23 for 20 and 29 independent 21 doubled 22 risk 23 for 26 disease 24 alzheimer 25 's 25 's 26 disease 26 disease 27 in 27 in 28 seven 29 independent 30 case 31 - 32 control 32 control 33 series 33 series 34 with 33 series 37 of 34 with 36 total 35 a 36 total 37 of 42 and 38 more 39 than 39 than 40 11,000 40 11,000 41 cases 41 cases 42 and 42 and 43 controls 42 and 44 of 44 of 46 descent 45 european 46 descent gene - based burden analyses in 4,387 cases and controls of european descent and 302 african american cases and controls , with complete sequence data for pld3 , reveal that several variants in this gene increase risk for alzheimer 's disease in both populations . 0 ###LEFT-WALL### 28 , 0 ###LEFT-WALL### 45 . 1 gene 2 - 1 gene 28 , 3 based 5 analyses 3 based 6 in 3 based 22 with 3 based 28 , 4 burden 5 analyses 6 in 7 4,387 7 4,387 9 and 7 4,387 11 of 8 cases 9 and 9 and 10 controls 11 of 19 and 12 european 13 descent 13 descent 14 and 14 and 18 cases 14 and 19 and 15 302 18 cases 16 african 17 american 17 american 18 cases 19 and 20 controls 19 and 21 , 22 with 25 data 23 complete 24 sequence 24 sequence 25 data 25 data 26 for 26 for 27 pld3 28 , 29 reveal 29 reveal 30 that 29 reveal 40 's 30 that 32 variants 30 that 36 increase 30 that 40 's 31 several 32 variants 32 variants 33 in 32 variants 36 increase 33 in 35 gene 34 this 35 gene 36 increase 37 risk 36 increase 38 for 38 for 39 alzheimer 40 's 41 disease 40 's 42 in 42 in 44 populations 43 both 44 populations pld3 is highly expressed in brain regions that are vulnerable to alzheimer 's disease pathology , including hippocampus and cortex , and is expressed at significantly lower levels in neurons from alzheimer 's disease brains compared to control brains . 0 ###LEFT-WALL### 1 pld3 0 ###LEFT-WALL### 22 and 0 ###LEFT-WALL### 40 . 1 pld3 22 and 2 is 4 expressed 2 is 22 and 3 highly 4 expressed 4 expressed 5 in 4 expressed 11 to 4 expressed 17 including 5 in 7 regions 6 brain 7 regions 7 regions 8 that 7 regions 9 are 8 that 9 are 9 are 10 vulnerable 11 to 15 pathology 12 alzheimer 13 's 13 's 15 pathology 14 disease 15 pathology 16 , 17 including 17 including 19 and 17 including 21 , 18 hippocampus 19 and 19 and 20 cortex 22 and 23 is 22 and 25 at 22 and 29 in 23 is 24 expressed 25 at 28 levels 26 significantly 27 lower 27 lower 28 levels 29 in 30 neurons 30 neurons 31 from 30 neurons 36 compared 31 from 35 brains 32 alzheimer 33 's 33 's 35 brains 34 disease 35 brains 36 compared 37 to 37 to 39 brains 38 control 39 brains overexpression of pld3 leads to a significant decrease in intracellular amyloid - β precursor protein ( app ) and extracellular aβ42 and aβ40 ( the 42 - and 40 - residue isoforms of the amyloid - β [peptide] ) , and knockdown of pld3 leads to a significant increase in extracellular aβ42 and aβ40 . 0 ###LEFT-WALL### 1 overexpression 0 ###LEFT-WALL### 4 leads 0 ###LEFT-WALL### 28 and 1 overexpression 2 of 1 overexpression 4 leads 2 of 3 pld3 4 leads 5 to 5 to 19 and 6 a 8 decrease 7 significant 8 decrease 8 decrease 9 in 8 decrease 19 and 9 in 15 protein 10 intracellular 15 protein 11 amyloid 12 - 11 amyloid 13 β 13 β 15 protein 14 precursor 15 protein 15 protein 17 app 16 ( 17 app 17 app 18 ) 19 and 23 aβ40 19 and 26 42 20 extracellular 23 aβ40 21 aβ42 22 and 22 and 23 aβ40 24 ( 26 42 25 the 26 42 26 42 27 - 27 - 28 and 28 and 29 40 28 and 30 - 29 40 30 - 30 - 53 and 31 residue 32 isoforms 32 isoforms 33 of 32 isoforms 41 and 33 of 35 amyloid 34 the 35 amyloid 35 amyloid 37 β 36 - 37 β 37 β 39 ) 40 , 41 and 41 and 42 knockdown 41 and 43 of 41 and 46 to 41 and 53 and 43 of 45 leads 44 pld3 45 leads 46 to 49 increase 47 a 49 increase 48 significant 49 increase 49 increase 50 in 50 in 52 aβ42 51 extracellular 52 aβ42 53 and 54 aβ40 53 and 55 . together , our genetic and functional data indicate that carriers of pld3 coding variants have a twofold increased risk for load and that pld3 influences app processing . 0 ###LEFT-WALL### 7 data 0 ###LEFT-WALL### 8 indicate 0 ###LEFT-WALL### 28 . 1 together 2 , 1 together 7 data 3 our 7 data 4 genetic 5 and 5 and 6 functional 5 and 7 data 7 data 8 indicate 8 indicate 22 and 9 that 10 carriers 9 that 15 have 9 that 22 and 10 carriers 11 of 10 carriers 13 coding 10 carriers 15 have 11 of 12 pld3 13 coding 14 variants 15 have 19 risk 16 a 19 risk 17 twofold 19 risk 18 increased 19 risk 19 risk 20 for 20 for 21 load 22 and 23 that 23 that 24 pld3 23 that 25 influences 24 pld3 25 influences 25 influences 27 processing 26 app 27 processing this study provides an example of how densely affected families may help to identify rare variants with large effects on risk for disease or other complex traits . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 provides 0 ###LEFT-WALL### 28 . 1 this 2 study 2 study 3 provides 3 provides 5 example 3 provides 20 on 4 an 5 example 5 example 6 of 5 example 17 with 6 of 7 how 7 how 8 densely 8 densely 9 affected 9 affected 10 families 10 families 11 may 11 may 12 help 12 help 13 to 12 help 14 identify 13 to 14 identify 14 identify 16 variants 15 rare 16 variants 17 with 19 effects 18 large 19 effects 20 on 21 risk 21 risk 22 for 22 for 27 traits 23 disease 24 or 24 or 25 other 24 or 27 traits 26 complex 27 traits objective : to determine the association between age at surgical [menopause] and both cognitive decline and alzheimer disease ( ad ) pathology in 2 longitudinal cohorts . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 27 . 2 : 3 to 2 : 4 determine 3 to 4 determine 4 determine 6 association 4 determine 7 between 4 determine 9 at 4 determine 23 in 5 the 6 association 7 between 8 age 9 at 22 pathology 10 surgical 12 and 12 and 15 decline 12 and 16 and 13 both 14 cognitive 14 cognitive 15 decline 16 and 18 disease 16 and 20 ad 16 and 22 pathology 17 alzheimer 18 disease 19 ( 20 ad 20 ad 21 ) 23 in 26 cohorts 24 2 26 cohorts 25 longitudinal 26 cohorts methods : female subjects from 2 longitudinal studies of cognitive decline [(] religious orders study and rush memory and aging project ) were included [(] total n = 1,884 ) . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 16 and 0 ###LEFT-WALL### 31 . 1 methods 2 : 2 : 4 subjects 3 female 4 subjects 4 subjects 5 from 5 from 8 studies 6 2 8 studies 7 longitudinal 8 studies 8 studies 9 of 9 of 15 study 10 cognitive 11 decline 11 decline 15 study 13 religious 15 study 14 orders 15 study 16 and 19 and 16 and 24 included 17 rush 18 memory 18 memory 19 and 19 and 21 project 19 and 22 ) 19 and 23 were 20 aging 21 project 23 were 24 included 24 included 26 total 26 total 28 = 27 n 28 = 28 = 29 1,884 28 = 30 ) the primary analysis examined the association between age at surgical [menopause] and decline in a global cognition score . 0 ###LEFT-WALL### 3 analysis 0 ###LEFT-WALL### 4 examined 0 ###LEFT-WALL### 19 . 1 the 3 analysis 2 primary 3 analysis 3 analysis 4 examined 4 examined 6 association 4 examined 7 between 4 examined 9 at 4 examined 14 in 5 the 6 association 7 between 8 age 9 at 12 and 10 surgical 12 and 12 and 13 decline 14 in 18 score 15 a 16 global 15 a 18 score 16 global 17 cognition 17 cognition 18 score secondary analyses examined additional outcomes : 1 [ )(decline in 5 cognitive subdomains and [2] [ )(a global measure of the burden of ad pathology . 0 ###LEFT-WALL### 2 analyses 0 ###LEFT-WALL### 3 examined 0 ###LEFT-WALL### 6 : 0 ###LEFT-WALL### 26 . 1 secondary 2 analyses 2 analyses 3 examined 3 examined 5 outcomes 4 additional 5 outcomes 6 : 14 and 7 1 9 )(decline 9 )(decline 10 in 9 )(decline 14 and 10 in 13 subdomains 11 5 13 subdomains 12 cognitive 13 subdomains 14 and 22 burden 14 and 23 of 17 )(a 18 global 17 )(a 19 measure 18 global 19 measure 19 measure 20 of 19 measure 22 burden 20 of 22 burden 21 the 22 burden 23 of 25 pathology 24 ad 25 pathology in exploratory analyses , we examined the effect of hormone replacement therapy ( hrt ) . 0 ###LEFT-WALL### 5 we 0 ###LEFT-WALL### 6 examined 0 ###LEFT-WALL### 16 . 1 in 3 analyses 1 in 4 , 1 in 5 we 2 exploratory 3 analyses 5 we 6 examined 6 examined 8 effect 7 the 8 effect 8 effect 9 of 9 of 12 therapy 10 hormone 12 therapy 11 replacement 12 therapy 12 therapy 14 hrt 13 ( 14 hrt 14 hrt 15 ) we adjusted all models for age , education , smoking , and cohort and stratified [by] surgical [vs] natural menopause . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 adjusted 0 ###LEFT-WALL### 21 . 1 we 2 adjusted 2 adjusted 4 models 3 all 4 models 4 models 5 for 5 for 14 and 6 age 7 , 7 , 8 education 7 , 9 , 9 , 10 smoking 9 , 12 and 11 , 12 and 12 and 13 cohort 12 and 14 and 14 and 20 menopause 15 stratified 20 menopause 17 surgical 20 menopause 19 natural 20 menopause results [:] for the 32 % of subjects with surgical [menopause] , earlier age at menopause [was] associated [with] faster decline [in] global cognition ( p = 0.0007 ) , specifically episodic memory ( p = 0.0003 ) and semantic memory ( p = 0.002 ) . 0 ###LEFT-WALL### 39 and 0 ###LEFT-WALL### 47 . 1 results 3 for 1 results 7 of 1 results 9 with 1 results 39 and 3 for 6 % 4 the 6 % 5 32 6 % 7 of 8 subjects 9 with 14 age 10 surgical 12 , 10 surgical 14 age 13 earlier 14 age 14 age 15 at 15 at 24 cognition 16 menopause 23 global 18 associated 21 decline 20 faster 21 decline 21 decline 23 global 23 global 24 cognition 24 cognition 27 = 24 cognition 33 memory 25 ( 27 = 26 p 27 = 27 = 28 0.0007 27 = 29 ) 30 , 31 specifically 30 , 33 memory 32 episodic 33 memory 33 memory 36 = 33 memory 38 ) 34 ( 36 = 35 p 36 = 36 = 37 0.0003 39 and 41 memory 39 and 44 = 40 semantic 41 memory 42 ( 44 = 43 p 44 = 44 = 45 0.002 44 = 46 ) earlier age [at] [menopause] was also associated with increased ad neuropathology ( p = 0.038 ) , in particular neuritic plaques ( p = 0.013 ) . 0 ###LEFT-WALL### 2 age 0 ###LEFT-WALL### 7 associated 0 ###LEFT-WALL### 27 . 1 earlier 2 age 2 age 5 was 5 was 7 associated 6 also 7 associated 7 associated 8 with 7 associated 11 neuropathology 8 with 10 ad 9 increased 10 ad 11 neuropathology 14 = 11 neuropathology 18 in 12 ( 14 = 13 p 14 = 14 = 15 0.038 14 = 16 ) 17 , 18 in 18 in 21 plaques 18 in 26 ) 19 particular 21 plaques 20 neuritic 21 plaques 21 plaques 24 = 22 ( 24 = 23 p 24 = 24 = 25 0.013 hrt use for at least 10 years , when administered within a 5 [-] year perimenopausal window , was associated with decreased decline [in] global cognition . 0 ###LEFT-WALL### 2 use 0 ###LEFT-WALL### 20 associated 0 ###LEFT-WALL### 27 . 1 hrt 2 use 2 use 3 for 2 use 19 was 3 for 7 years 4 at 5 least 5 least 6 10 6 10 7 years 8 , 9 when 9 when 10 administered 9 when 18 , 9 when 19 was 10 administered 11 within 11 within 17 window 12 a 17 window 13 5 15 year 15 year 17 window 16 perimenopausal 17 window 19 was 20 associated 20 associated 21 with 21 with 26 cognition 22 decreased 23 decline 23 decline 26 cognition 25 global 26 cognition no associations were [seen] in women who had natural [menopause] . 0 ###LEFT-WALL### 2 associations 0 ###LEFT-WALL### 3 were 0 ###LEFT-WALL### 11 . 1 no 2 associations 2 associations 3 were 3 were 5 in 3 were 9 natural 5 in 6 women 6 women 7 who 6 women 8 had 7 who 8 had conclusions : early age [at] surgical menopause [was] associated [with] cognitive decline and ad neuropathology . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 12 decline 2 : 13 and 2 : 16 . 3 early 4 age 4 age 9 associated 6 surgical 7 menopause 7 menopause 9 associated 9 associated 12 decline 11 cognitive 12 decline 13 and 14 ad 13 and 15 neuropathology 14 ad 15 neuropathology ongoing studies should clarify the potential effect of hrt on this relationship . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 4 clarify 0 ###LEFT-WALL### 13 . 1 ongoing 2 studies 2 studies 3 should 3 should 4 clarify 4 clarify 7 effect 4 clarify 10 on 5 the 7 effect 6 potential 7 effect 7 effect 8 of 8 of 9 hrt 10 on 12 relationship 11 this 12 relationship none this [article] is addressed to endocrinologists treating patients with diabetic complications as well as to basic scientists studying an elusive link between diseases and aging . 0 ###LEFT-WALL### 1 none 0 ###LEFT-WALL### 7 endocrinologists 0 ###LEFT-WALL### 27 . 1 none 2 this 1 none 6 to 1 none 7 endocrinologists 2 this 4 is 4 is 5 addressed 5 addressed 6 to 7 endocrinologists 9 patients 7 endocrinologists 10 with 7 endocrinologists 16 to 8 treating 9 patients 10 with 12 complications 11 diabetic 12 complications 12 complications 13 as 13 as 14 well 15 as 16 to 16 to 18 scientists 17 basic 18 scientists 18 scientists 19 studying 19 studying 22 link 19 studying 23 between 20 an 21 elusive 20 an 22 link 21 elusive 22 link 23 between 25 and 24 diseases 25 and 25 and 26 aging it answers some challenging questions . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 2 answers 0 ###LEFT-WALL### 6 . 1 it 2 answers 2 answers 5 questions 3 some 5 questions 4 challenging 5 questions what is the link between insulin resistance ( ir ) , cellular aging and diseases ? 0 ###LEFT-WALL### 1 what 0 ###LEFT-WALL### 2 is 1 what 2 is 2 is 4 link 3 the 4 link 4 link 5 between 5 between 7 resistance 6 insulin 7 resistance 7 resistance 9 ir 7 resistance 14 and 8 ( 9 ir 9 ir 10 ) 11 , 14 and 12 cellular 13 aging 12 cellular 14 and 14 and 15 diseases 14 and 16 ? why complications such as retinopathy may paradoxically precede the onset of type ii [diabetes] . 0 ###LEFT-WALL### 2 complications 0 ###LEFT-WALL### 8 precede 0 ###LEFT-WALL### 15 . 1 why 2 complications 2 complications 4 as 2 complications 6 may 3 such 4 as 4 as 5 retinopathy 6 may 8 precede 7 paradoxically 8 precede 8 precede 10 onset 9 the 10 onset 10 onset 11 of 11 of 12 type 12 type 13 ii why intensive insulin therapy may initially worsen retinopathy . 0 ###LEFT-WALL### 4 therapy 0 ###LEFT-WALL### 7 worsen 0 ###LEFT-WALL### 9 . 1 why 4 therapy 2 intensive 3 insulin 3 insulin 4 therapy 4 therapy 5 may 5 may 7 worsen 6 initially 7 worsen 7 worsen 8 retinopathy how [nutrient] - and insulin - sensing mammalian target [of] rapamycin ( mtor ) pathway can drive insulin resistance and diabetic complications . 0 ###LEFT-WALL### 20 and 0 ###LEFT-WALL### 23 . 1 how 4 and 3 - 4 and 4 and 5 insulin 4 and 7 sensing 4 and 15 pathway 6 - 7 sensing 7 sensing 11 rapamycin 7 sensing 14 ) 8 mammalian 9 target 9 target 11 rapamycin 11 rapamycin 13 mtor 12 ( 13 mtor 13 mtor 14 ) 15 pathway 19 resistance 16 can 19 resistance 17 drive 19 resistance 18 insulin 19 resistance 19 resistance 20 and 20 and 22 complications 21 diabetic 22 complications and [how] rapamycin , at rational doses and schedules , may prevent ir , retinopathy , nephropathy and beta - cell failure , without causing side effects . 0 ###LEFT-WALL### 1 and 0 ###LEFT-WALL### 28 . 1 and 3 rapamycin 1 and 12 prevent 3 rapamycin 5 at 3 rapamycin 11 may 4 , 5 at 5 at 8 and 5 at 10 , 6 rational 7 doses 7 doses 8 and 8 and 9 schedules 11 may 12 prevent 12 prevent 18 and 12 prevent 24 without 13 ir 14 , 14 , 15 retinopathy 14 , 16 , 16 , 17 nephropathy 16 , 18 and 18 and 19 beta 18 and 22 failure 20 - 22 failure 21 cell 22 failure 22 failure 23 , 24 without 25 causing 25 causing 27 effects 26 side 27 effects satellite [cell] ( sc ) [proliferation] and differentiation have critical roles in skeletal muscle recovery after injury and adaptation in response to hypertrophic stimuli . 0 ###LEFT-WALL### 7 and 0 ###LEFT-WALL### 9 have 0 ###LEFT-WALL### 25 . 1 satellite 4 sc 1 satellite 7 and 3 ( 4 sc 4 sc 5 ) 7 and 8 differentiation 7 and 9 have 9 have 11 roles 9 have 12 in 9 have 16 after 9 have 22 to 10 critical 11 roles 12 in 15 recovery 13 skeletal 14 muscle 14 muscle 15 recovery 16 after 18 and 17 injury 18 and 18 and 19 adaptation 20 in 21 response 21 response 22 to 22 to 24 stimuli 23 hypertrophic 24 stimuli normal ageing hinders sc proliferation [and] differentiation , and is associated with increased expression of a number [of] pro - apoptotic factors in skeletal muscle . 0 ###LEFT-WALL### 2 ageing 0 ###LEFT-WALL### 9 and 1 normal 2 ageing 2 ageing 9 and 3 hinders 7 differentiation 3 hinders 9 and 4 sc 7 differentiation 5 proliferation 7 differentiation 8 , 9 and 9 and 10 is 9 and 12 with 10 is 11 associated 12 with 14 expression 13 increased 14 expression 14 expression 15 of 14 expression 22 factors 15 of 19 pro 16 a 19 pro 17 number 19 pro 20 - 22 factors 21 apoptotic 22 factors 22 factors 23 in 22 factors 26 . 23 in 25 muscle 24 skeletal 25 muscle in light of previous studies that have demonstrated age - related altered expression of genes involved in sc antioxidant and repair activity , this investigation was aimed at evaluating the incidence of apoptotic features in human scs . 0 ###LEFT-WALL### 9 age 0 ###LEFT-WALL### 11 related 0 ###LEFT-WALL### 23 , 0 ###LEFT-WALL### 38 . 1 in 2 light 1 in 9 age 2 light 3 of 3 of 5 studies 4 previous 5 studies 5 studies 6 that 5 studies 7 have 6 that 7 have 7 have 8 demonstrated 10 - 11 related 11 related 13 expression 11 related 17 in 12 altered 13 expression 13 expression 14 of 13 expression 16 involved 14 of 15 genes 17 in 20 and 18 sc 19 antioxidant 19 antioxidant 20 and 20 and 22 activity 21 repair 22 activity 23 , 25 investigation 23 , 27 aimed 24 this 25 investigation 25 investigation 26 was 26 was 27 aimed 27 aimed 28 at 28 at 29 evaluating 29 evaluating 31 incidence 29 evaluating 35 in 30 the 31 incidence 31 incidence 32 of 32 of 34 features 33 apoptotic 34 features 35 in 37 scs 36 human 37 scs primary cells were obtained from vastus lateralis of nine young ( 27.3±2.0 years old [ )(and nine old ( 71.1±1.8 years old ) subjects , and cultured in complete medium [for] analyses at 4 , 24 , 48 , [and] 72 h . 1 primary 2 cells 1 primary 3 were 1 primary 4 obtained 1 primary 16 )(and 1 primary 26 and 2 cells 3 were 4 obtained 5 from 4 obtained 10 young 5 from 7 lateralis 6 vastus 7 lateralis 7 lateralis 8 of 8 of 9 nine 11 ( 16 )(and 12 27.3±2.0 14 old 12 27.3±2.0 16 )(and 13 years 14 old 16 )(and 18 old 16 )(and 20 71.1±1.8 16 )(and 23 ) 17 nine 18 old 19 ( 20 71.1±1.8 20 71.1±1.8 22 old 20 71.1±1.8 23 ) 21 years 22 old 24 subjects 26 and 25 , 26 and 26 and 27 cultured 26 and 28 in 26 and 33 at 26 and 42 h 28 in 32 analyses 29 complete 32 analyses 30 medium 32 analyses 33 at 34 4 34 4 36 24 34 4 38 48 35 , 36 24 36 24 37 , 37 , 38 48 38 48 39 , 41 72 42 h 42 h 43 . apoptosis was assessed using annexinv/propidium iodide staining , the terminal deoxynucleotidyl transferase dutp nick - end labelling technique , rt - pcr , dna microarrays , flow cytometry , and immunofluorescence analysis . 0 ###LEFT-WALL### 1 apoptosis 0 ###LEFT-WALL### 3 assessed 1 apoptosis 2 was 2 was 3 assessed 3 assessed 4 using 4 using 6 iodide 5 annexinv/propidium 6 iodide 6 iodide 7 staining 6 iodide 14 nick 6 iodide 20 rt 8 , 14 nick 9 the 14 nick 10 terminal 11 deoxynucleotidyl 11 deoxynucleotidyl 14 nick 12 transferase 13 dutp 13 dutp 14 nick 14 nick 18 technique 14 nick 19 , 15 - 18 technique 16 end 18 technique 17 labelling 18 technique 18 technique 19 , 19 , 20 rt 20 rt 30 and 20 rt 33 . 21 - 30 and 22 pcr 23 , 23 , 25 microarrays 23 , 26 , 24 dna 25 microarrays 26 , 28 cytometry 26 , 30 and 27 flow 28 cytometry 29 , 30 and 30 and 32 analysis 30 and 33 . 31 immunofluorescence 32 analysis there was an increased rate of apoptotic cells in aged subjects at all of the experimental time points , with no direct correlation between annexinv - positive cells and caspase - 8 activity . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 was 1 there 2 was 2 was 5 rate 3 an 5 rate 4 increased 5 rate 5 rate 6 of 5 rate 12 at 6 of 8 cells 7 apoptotic 8 cells 8 cells 9 in 9 in 11 subjects 10 aged 11 subjects 12 at 18 points 13 all 14 of 13 all 18 points 14 of 18 points 15 the 18 points 16 experimental 18 points 17 time 18 points 18 points 20 with 18 points 29 and 19 , 20 with 20 with 23 correlation 20 with 24 between 20 with 26 - 21 no 23 correlation 22 direct 23 correlation 24 between 25 annexinv 26 - 29 and 27 positive 28 cells 28 cells 29 and 29 and 30 caspase 29 and 33 activity 29 and 34 . 31 - 33 activity 32 8 33 activity 33 activity 34 . on the other hand , casp2 , casp6 , casp7 , and casp9 and a number of cell death genes were upregulated in the aged scs . 0 ###LEFT-WALL### 14 and 0 ###LEFT-WALL### 22 upregulated 0 ###LEFT-WALL### 27 . 1 on 4 hand 1 on 5 , 1 on 14 and 2 the 3 other 3 other 4 hand 6 casp2 7 , 7 , 8 casp6 7 , 12 and 8 casp6 10 casp7 9 , 10 casp7 10 casp7 11 , 12 and 13 casp9 12 and 14 and 14 and 16 number 14 and 17 of 14 and 21 were 15 a 16 number 17 of 20 genes 18 cell 20 genes 19 death 20 genes 21 were 22 upregulated 22 upregulated 23 in 23 in 26 scs 24 the 26 scs 25 aged 26 scs altogether , our data show age - related enhanced susceptibility of human scs to apoptosis , which might be responsible for their reduced response to muscle damage . 0 ###LEFT-WALL### 4 data 0 ###LEFT-WALL### 5 show 0 ###LEFT-WALL### 8 related 0 ###LEFT-WALL### 16 , 0 ###LEFT-WALL### 28 . 1 altogether 2 , 1 altogether 4 data 3 our 4 data 4 data 5 show 5 show 6 age 7 - 8 related 8 related 10 susceptibility 8 related 14 to 8 related 16 , 9 enhanced 10 susceptibility 10 susceptibility 11 of 11 of 13 scs 12 human 13 scs 14 to 15 apoptosis 16 , 17 which 16 , 26 muscle 17 which 18 might 18 might 19 be 19 be 20 responsible 20 responsible 21 for 20 responsible 25 to 21 for 24 response 22 their 24 response 23 reduced 24 response 25 to 26 muscle 26 muscle 27 damage the intersection of aging and hiv/aids is a looming ['] epidemic within an epidemic . ['] 0 ###LEFT-WALL### 2 intersection 0 ###LEFT-WALL### 7 is 0 ###LEFT-WALL### 15 . 1 the 2 intersection 2 intersection 3 of 2 intersection 7 is 3 of 5 and 4 aging 5 and 5 and 6 hiv/aids 7 is 11 epidemic 8 a 11 epidemic 9 looming 11 epidemic 11 epidemic 12 within 12 within 14 epidemic 13 an 14 epidemic [this] paper reviews how [hiv/aids] and its therapy cause premature aging or contribute mechanistically to hiv - associated [non] - aids illnesses ( hana ) . 0 ###LEFT-WALL### 2 paper 0 ###LEFT-WALL### 26 . 2 paper 3 reviews 3 reviews 6 and 3 reviews 13 contribute 4 how 6 and 6 and 8 therapy 6 and 12 or 7 its 8 therapy 9 cause 11 aging 9 cause 12 or 10 premature 11 aging 12 or 13 contribute 13 contribute 14 mechanistically 13 contribute 15 to 15 to 16 hiv 16 hiv 18 associated 16 hiv 22 illnesses 17 - 18 associated 18 associated 20 - 20 - 22 illnesses 21 aids 22 illnesses 22 illnesses 24 hana 22 illnesses 25 ) 23 ( 24 hana 24 hana 25 ) survival with hiv/aids has markedly improved by therapy combinations containing nucleoside reverse transcriptase inhibitors ( nrtis ) , [non] - nucleoside reverse transcriptase inhibitors , and protease inhibitors ( pis ) called haart ( highly active antiretroviral therapy ) . 0 ###LEFT-WALL### 1 survival 0 ###LEFT-WALL### 6 improved 0 ###LEFT-WALL### 18 , 0 ###LEFT-WALL### 40 . 1 survival 2 with 1 survival 4 has 2 with 3 hiv/aids 4 has 6 improved 5 markedly 6 improved 6 improved 7 by 7 by 9 combinations 8 therapy 9 combinations 9 combinations 10 containing 9 combinations 16 nrtis 10 containing 14 inhibitors 11 nucleoside 12 reverse 12 reverse 14 inhibitors 13 transcriptase 14 inhibitors 15 ( 16 nrtis 16 nrtis 17 ) 18 , 20 - 18 , 32 called 20 - 26 and 21 nucleoside 24 inhibitors 22 reverse 24 inhibitors 23 transcriptase 24 inhibitors 24 inhibitors 26 and 25 , 26 and 26 and 28 inhibitors 26 and 30 pis 26 and 32 called 27 protease 28 inhibitors 29 ( 30 pis 30 pis 31 ) 32 called 33 haart 33 haart 38 therapy 34 ( 38 therapy 35 highly 36 active 36 active 38 therapy 37 antiretroviral 38 therapy 38 therapy 39 ) because nrtis and pis together [prevent] [or] attenuate hiv - 1 replication , and prolong life , the population of aging patients with hiv/aids increases accordingly . 0 ###LEFT-WALL### 19 population 0 ###LEFT-WALL### 25 increases 0 ###LEFT-WALL### 27 . 1 because 3 and 1 because 14 and 1 because 17 , 1 because 19 population 2 nrtis 3 and 3 and 4 pis 3 and 14 and 5 together 8 attenuate 8 attenuate 9 hiv 8 attenuate 14 and 9 hiv 12 replication 10 - 12 replication 11 1 12 replication 12 replication 13 , 13 , 14 and 14 and 15 prolong 15 prolong 16 life 18 the 19 population 19 population 20 of 19 population 25 increases 20 of 21 aging 21 aging 22 patients 21 aging 23 with 23 with 24 hiv/aids 25 increases 26 accordingly however , illnesses frequently associated with aging in the absence of hiv/aids appear to occur prematurely in hiv/aids patients . 0 ###LEFT-WALL### 3 illnesses 0 ###LEFT-WALL### 13 appear 0 ###LEFT-WALL### 20 . 1 however 2 , 1 however 3 illnesses 3 illnesses 5 associated 3 illnesses 13 appear 4 frequently 5 associated 5 associated 6 with 6 with 7 aging 7 aging 8 in 8 in 10 absence 9 the 10 absence 10 absence 11 of 11 of 12 hiv/aids 13 appear 14 to 13 appear 15 occur 14 to 15 occur 15 occur 16 prematurely 15 occur 17 in 17 in 19 patients 18 hiv/aids 19 patients theories that help to explain biological aging include oxidative stress ( where mitochondrial oxidative injury exceeds antioxidant defense ) , chromosome telomere shortening with associated cellular senescence , and accumulation of lamin a precursors ( a nuclear [envelop] protein ) . 0 ###LEFT-WALL### 1 theories 0 ###LEFT-WALL### 8 include 0 ###LEFT-WALL### 41 . 1 theories 2 that 1 theories 3 help 1 theories 8 include 2 that 3 help 3 help 4 to 3 help 5 explain 4 to 5 explain 5 explain 7 aging 6 biological 7 aging 8 include 10 stress 9 oxidative 10 stress 10 stress 12 where 10 stress 23 shortening 11 ( 12 where 12 where 15 injury 12 where 16 exceeds 12 where 19 ) 13 mitochondrial 15 injury 14 oxidative 15 injury 15 injury 16 exceeds 16 exceeds 18 defense 17 antioxidant 18 defense 20 , 23 shortening 21 chromosome 23 shortening 22 telomere 23 shortening 23 shortening 24 with 23 shortening 31 of 23 shortening 39 protein 23 shortening 40 ) 24 with 29 and 25 associated 27 senescence 26 cellular 27 senescence 27 senescence 29 and 28 , 29 and 29 and 30 accumulation 31 of 34 precursors 32 lamin 33 a 32 lamin 34 precursors 35 ( 39 protein 36 a 37 nuclear 36 a 39 protein 37 nuclear 39 protein 39 protein 40 ) each of these has the potential to be enhanced or caused by hiv/aids , antiretroviral therapy , or both . 0 ###LEFT-WALL### 1 each 0 ###LEFT-WALL### 4 has 0 ###LEFT-WALL### 20 . 1 each 2 of 1 each 4 has 2 of 3 these 4 has 6 potential 4 has 7 to 4 has 12 by 5 the 6 potential 7 to 10 or 8 be 9 enhanced 8 be 10 or 10 or 11 caused 12 by 18 or 13 hiv/aids 16 therapy 13 hiv/aids 18 or 14 , 16 therapy 15 antiretroviral 16 therapy 16 therapy 17 , 18 or 19 both antiretroviral therapy has been shown to enhance events seen in biological aging . 0 ###LEFT-WALL### 2 therapy 0 ###LEFT-WALL### 5 shown 0 ###LEFT-WALL### 13 . 1 antiretroviral 2 therapy 2 therapy 3 has 3 has 4 been 4 been 5 shown 5 shown 6 to 6 to 7 enhance 7 enhance 8 events 8 events 9 seen 9 seen 10 in 10 in 12 aging 11 biological 12 aging specifically , antiretroviral nrtis cause mitochondrial dysfunction , oxidative stress , and mitochondrial dna defects that resemble features of both hana and aging . 0 ###LEFT-WALL### 4 nrtis 0 ###LEFT-WALL### 5 cause 0 ###LEFT-WALL### 24 . 1 specifically 2 , 1 specifically 4 nrtis 3 antiretroviral 4 nrtis 4 nrtis 5 cause 5 cause 12 and 6 mitochondrial 7 dysfunction 7 dysfunction 8 , 8 , 10 stress 8 , 12 and 9 oxidative 10 stress 11 , 12 and 12 and 15 defects 12 and 16 that 12 and 17 resemble 13 mitochondrial 15 defects 14 dna 15 defects 16 that 17 resemble 17 resemble 18 features 18 features 19 of 19 of 22 and 20 both 22 and 21 hana 22 and 22 and 23 aging more recent clinical evidence points to telomere shortening caused by nrti triphosphate - induced inhibition of telomerase , suggesting telomerase reverse transcriptase ( tert ) inhibition as being a pathogenetic contributor to premature aging in hiv/aids . 0 ###LEFT-WALL### 4 evidence 0 ###LEFT-WALL### 5 points 0 ###LEFT-WALL### 37 . 1 more 4 evidence 2 recent 4 evidence 3 clinical 4 evidence 4 evidence 5 points 5 points 6 to 5 points 10 by 5 points 27 as 5 points 31 contributor 5 points 32 to 6 to 7 telomere 7 telomere 8 shortening 7 telomere 9 caused 10 by 26 inhibition 11 nrti 26 inhibition 12 triphosphate 15 inhibition 12 triphosphate 26 inhibition 13 - 15 inhibition 14 induced 15 inhibition 15 inhibition 16 of 15 inhibition 19 suggesting 15 inhibition 25 ) 16 of 17 telomerase 18 , 19 suggesting 19 suggesting 20 telomerase 19 suggesting 21 reverse 19 suggesting 25 ) 21 reverse 22 transcriptase 22 transcriptase 24 tert 23 ( 24 tert 24 tert 25 ) 27 as 28 being 29 a 30 pathogenetic 29 a 31 contributor 30 pathogenetic 31 contributor 32 to 34 aging 33 premature 34 aging 34 aging 35 in 35 in 36 hiv/aids pis may also have a role in premature aging in hiv/aids as they cause prelamin a accumulation . 0 ###LEFT-WALL### 1 pis 0 ###LEFT-WALL### 4 have 1 pis 2 may 2 may 4 have 3 also 4 have 4 have 6 role 4 have 7 in 4 have 10 in 5 a 6 role 7 in 9 aging 8 premature 9 aging 10 in 11 hiv/aids 11 hiv/aids 14 cause 12 as 13 they 12 as 14 cause 13 they 14 cause 14 cause 17 accumulation 14 cause 18 . 15 prelamin 16 a 15 prelamin 17 accumulation overall , toxic side effects of haart may both resemble and [promote] events of aging [and] are worthy of mechanistic studies . 0 ###LEFT-WALL### 1 overall 0 ###LEFT-WALL### 2 , 0 ###LEFT-WALL### 22 . 2 , 3 toxic 2 , 4 side 2 , 11 and 3 toxic 4 side 4 side 5 effects 5 effects 6 of 6 of 7 haart 7 haart 8 may 7 haart 10 resemble 8 may 9 both 8 may 10 resemble 11 and 13 events 11 and 17 are 13 events 14 of 13 events 17 are 14 of 15 aging 17 are 18 worthy 18 worthy 19 of 19 of 21 studies 20 mechanistic 21 studies none background : america 's racial and ethnic composition is changing so rapidly that minority groups are expected to constitute almost half of the u.s [.] population by 2060 . 0 ###LEFT-WALL### 1 none 0 ###LEFT-WALL### 12 so 0 ###LEFT-WALL### 30 . 2 background 3 : 3 : 7 and 4 america 5 's 5 's 7 and 6 racial 7 and 7 and 8 ethnic 7 and 9 composition 7 and 11 changing 9 composition 10 is 10 is 11 changing 11 changing 12 so 12 so 15 minority 12 so 18 expected 13 rapidly 15 minority 14 that 15 minority 15 minority 16 groups 15 minority 17 are 15 minority 18 expected 16 groups 17 are 18 expected 19 to 18 expected 20 constitute 19 to 20 constitute 20 constitute 22 half 21 almost 22 half 22 half 23 of 22 half 28 by 23 of 27 population 24 the 27 population 25 u.s 27 population 28 by 29 2060 special efforts are needed to effectively recruit and retain members of racial and ethnic minority groups in health - related research studies , but the information available on time and costs associated with their recruitment is limited . 0 ###LEFT-WALL### 2 efforts 0 ###LEFT-WALL### 20 related 0 ###LEFT-WALL### 24 but 0 ###LEFT-WALL### 38 . 1 special 2 efforts 2 efforts 3 are 3 are 8 and 4 needed 5 to 4 needed 8 and 5 to 7 recruit 6 effectively 7 recruit 8 and 9 retain 9 retain 10 members 9 retain 17 in 10 members 11 of 11 of 16 groups 12 racial 13 and 13 and 14 ethnic 13 and 15 minority 15 minority 16 groups 17 in 18 health 19 - 20 related 20 related 22 studies 20 related 23 , 21 research 22 studies 24 but 26 information 24 but 36 is 25 the 26 information 26 information 27 available 26 information 32 associated 26 information 36 is 27 available 28 on 28 on 30 and 29 time 30 and 30 and 31 costs 32 associated 33 with 33 with 35 recruitment 34 their 35 recruitment 36 is 37 limited objectives : the aim of this study was to describe and [compare] the time and monetary costs associated with recruiting and interviewing a diverse sample of older adults living in south florida . 0 ###LEFT-WALL### 1 objectives 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 33 . 1 objectives 2 : 2 : 4 aim 3 the 4 aim 4 aim 5 of 4 aim 7 study 4 aim 10 describe 5 of 6 this 7 study 8 was 8 was 9 to 8 was 10 describe 9 to 10 describe 11 and 15 and 11 and 18 associated 13 the 14 time 14 time 15 and 15 and 17 costs 15 and 18 associated 16 monetary 17 costs 18 associated 19 with 18 associated 25 sample 19 with 21 and 20 recruiting 21 and 21 and 22 interviewing 23 a 25 sample 24 diverse 25 sample 25 sample 26 of 25 sample 29 living 26 of 28 adults 27 older 28 adults 29 living 30 in 30 in 32 florida 31 south 32 florida methods : men and women aged 60 years and older from four ethnic groups - african american , afro - caribbean , hispanic american , and european american - were recruited to participate in a longitudinal study of healthy aging . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 41 . 2 : 4 and 2 : 6 aged 2 : 15 - 2 : 22 , 3 men 4 and 4 and 5 women 4 and 6 aged 6 aged 9 and 7 60 8 years 8 years 9 and 9 and 10 older 10 older 11 from 11 from 14 groups 12 four 14 groups 13 ethnic 14 groups 15 - 19 afro 16 african 19 afro 17 american 18 , 17 american 19 afro 19 afro 21 caribbean 20 - 21 caribbean 21 caribbean 22 , 22 , 23 hispanic 22 , 31 recruited 23 hispanic 26 and 23 hispanic 30 were 23 hispanic 31 recruited 24 american 26 and 25 , 26 and 26 and 28 american 26 and 29 - 26 and 30 were 27 european 28 american 31 recruited 32 to 32 to 33 participate 33 participate 34 in 34 in 37 study 35 a 36 longitudinal 35 a 37 study 36 longitudinal 37 study 37 study 38 of 38 of 40 aging 39 healthy 40 aging costs for study activities ( including recruitment [,] scheduling sessions , interviewing , file scoring , log updating , blood specimen analysis and storage , data analysis , and monetary compensation to participants ) were determined after 100 weeks of data [collection] . 0 ###LEFT-WALL### 1 costs 0 ###LEFT-WALL### 16 , 0 ###LEFT-WALL### 43 . 1 costs 2 for 1 costs 4 activities 1 costs 14 file 1 costs 15 scoring 2 for 3 study 4 activities 6 including 4 activities 14 file 5 ( 6 including 6 including 10 sessions 6 including 12 interviewing 6 including 13 , 7 recruitment 10 sessions 9 scheduling 10 sessions 11 , 12 interviewing 12 interviewing 13 , 15 scoring 16 , 16 , 23 and 16 , 35 were 17 log 18 updating 18 updating 19 , 19 , 22 analysis 19 , 23 and 20 blood 21 specimen 21 specimen 22 analysis 23 and 24 storage 23 and 25 , 23 and 29 and 23 and 35 were 25 , 29 and 26 data 27 analysis 27 analysis 29 and 28 , 29 and 29 and 31 compensation 29 and 32 to 29 and 34 ) 30 monetary 31 compensation 32 to 33 participants 35 were 36 determined 36 determined 37 after 37 after 39 weeks 38 100 39 weeks 39 weeks 40 of 40 of 41 data results : altogether , 483 participants completed the study in the first 100 weeks . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 6 participants 2 : 7 completed 2 : 15 . 3 altogether 4 , 3 altogether 6 participants 5 483 6 participants 6 participants 7 completed 7 completed 9 study 7 completed 10 in 8 the 9 study 10 in 14 weeks 11 the 12 first 11 the 13 100 13 100 14 weeks the total cost for each participant ranged from $ 265 to $ 576 . 0 ###LEFT-WALL### 3 cost 0 ###LEFT-WALL### 7 ranged 0 ###LEFT-WALL### 14 . 1 the 3 cost 2 total 3 cost 3 cost 4 for 3 cost 7 ranged 4 for 6 participant 5 each 6 participant 7 ranged 8 from 8 from 11 to 9 $ 10 265 9 $ 11 to 11 to 12 $ 12 $ 13 576 each successful enrollment required an average of 1.83 hours for recruitment [and] scheduling of the interviews . 0 ###LEFT-WALL### 3 enrollment 0 ###LEFT-WALL### 4 required 0 ###LEFT-WALL### 17 . 1 each 3 enrollment 2 successful 3 enrollment 3 enrollment 4 required 4 required 6 average 5 an 6 average 6 average 7 of 7 of 9 hours 8 1.83 9 hours 9 hours 10 for 10 for 13 scheduling 11 recruitment 13 scheduling 13 scheduling 14 of 14 of 16 interviews 15 the 16 interviews the time [to] interview african american and afro - caribbeans was greater than the time needed to interview hispanic american and european american participants . 0 ###LEFT-WALL### 7 and 0 ###LEFT-WALL### 13 than 0 ###LEFT-WALL### 25 . 1 the 6 american 2 time 5 african 4 interview 5 african 5 african 6 american 6 american 7 and 7 and 8 afro 7 and 9 - 10 caribbeans 11 was 11 was 12 greater 12 greater 13 than 13 than 15 time 13 than 16 needed 14 the 15 time 15 time 16 needed 16 needed 17 to 17 to 18 interview 18 interview 24 participants 19 hispanic 23 american 20 american 21 and 21 and 22 european 21 and 23 american 23 american 24 participants discussion : to develop more accurate budgets for recruitment [of] minority individuals into research studies and to use the limited resources in an effective way , careful planning and ongoing monitoring of costs are essential . 0 ###LEFT-WALL### 1 discussion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 36 . 2 : 29 and 2 : 34 are 3 to 16 and 3 to 26 , 3 to 29 and 4 develop 7 budgets 4 develop 16 and 5 more 6 accurate 6 accurate 7 budgets 7 budgets 8 for 8 for 12 individuals 9 recruitment 11 minority 11 minority 12 individuals 12 individuals 13 into 13 into 15 studies 14 research 15 studies 16 and 17 to 16 and 18 use 16 and 22 in 17 to 18 use 18 use 21 resources 19 the 21 resources 20 limited 21 resources 22 in 25 way 23 an 24 effective 23 an 25 way 24 effective 25 way 27 careful 28 planning 28 planning 29 and 29 and 31 monitoring 29 and 34 are 30 ongoing 31 monitoring 31 monitoring 32 of 32 of 33 costs 34 are 35 essential background : although telomere shortening occurs as a natural part of aging , there is now a robust body of research that suggests that there is a relationship between psychosocial , environmental , and behavioral factors and changes in telomere length . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 13 , 0 ###LEFT-WALL### 42 . 1 background 2 : 2 : 3 although 2 : 7 as 3 although 4 telomere 3 although 6 occurs 4 telomere 5 shortening 4 telomere 6 occurs 7 as 10 part 8 a 10 part 9 natural 10 part 10 part 11 of 11 of 12 aging 13 , 37 and 14 there 37 and 15 is 16 now 15 is 19 body 15 is 37 and 17 a 19 body 18 robust 19 body 19 body 20 of 19 body 24 that 19 body 26 is 20 of 21 research 21 research 22 that 21 research 23 suggests 22 that 23 suggests 24 that 25 there 24 that 26 is 26 is 28 relationship 26 is 29 between 27 a 28 relationship 29 between 36 factors 30 psychosocial 31 , 30 psychosocial 36 factors 32 environmental 34 and 33 , 34 and 34 and 35 behavioral 34 and 36 factors 37 and 38 changes 38 changes 39 in 38 changes 41 length 40 telomere 41 length these factors need to be considered when integrating telomere measurement in biobehavioral research studies . 0 ###LEFT-WALL### 2 factors 0 ###LEFT-WALL### 3 need 0 ###LEFT-WALL### 15 . 1 these 2 factors 2 factors 3 need 3 need 4 to 3 need 6 considered 4 to 5 be 5 be 6 considered 6 considered 7 when 7 when 8 integrating 7 when 14 studies 8 integrating 10 measurement 8 integrating 11 in 8 integrating 14 studies 9 telomere 10 measurement 11 in 13 research 12 biobehavioral 13 research objectives : this article provides a brief summary of the known facts about telomere biology and an integrative review of current human research studies that assessed relationships between psychosocial , environmental , or behavioral factors and telomere length . 0 ###LEFT-WALL### 1 objectives 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 26 assessed 0 ###LEFT-WALL### 39 . 2 : 4 article 2 : 5 provides 3 this 4 article 4 article 5 provides 5 provides 8 summary 5 provides 13 about 6 a 8 summary 7 brief 8 summary 8 summary 9 of 9 of 12 facts 10 the 12 facts 11 known 12 facts 13 about 16 and 14 telomere 15 biology 15 biology 16 and 16 and 19 review 16 and 20 of 17 an 19 review 18 integrative 19 review 20 of 24 studies 21 current 24 studies 22 human 23 research 23 research 24 studies 24 studies 25 that 24 studies 26 assessed 25 that 26 assessed 26 assessed 27 relationships 27 relationships 28 between 28 between 36 and 29 psychosocial 30 , 29 psychosocial 35 factors 31 environmental 33 or 32 , 33 or 33 or 34 behavioral 33 or 35 factors 35 factors 36 and 36 and 38 length 37 telomere 38 length methods : an integrative review was conducted to examine human research studies that focused on psychosocial , environmental , and behavioral factors affecting telomere length and telomerase activity using the electronic databases pubmed/medline and cinahl from 2003 to the present . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 41 . 2 : 5 review 2 : 7 conducted 2 : 17 , 3 an 5 review 4 integrative 5 review 5 review 6 was 6 was 7 conducted 7 conducted 8 to 7 conducted 16 psychosocial 8 to 9 examine 9 examine 12 studies 10 human 12 studies 11 research 12 studies 12 studies 13 that 12 studies 15 on 13 that 14 focused 14 focused 15 on 17 , 34 and 18 environmental 20 and 19 , 20 and 20 and 24 telomere 20 and 25 length 21 behavioral 24 telomere 22 factors 24 telomere 23 affecting 24 telomere 25 length 26 and 26 and 28 activity 26 and 34 and 27 telomerase 28 activity 28 activity 29 using 29 using 33 pubmed/medline 30 the 32 databases 31 electronic 32 databases 32 databases 33 pubmed/medline 34 and 35 cinahl 34 and 36 from 34 and 38 to 36 from 37 2003 38 to 40 present 39 the 40 present in addition to the known individual factors that are associated with telomere length , the results of the integrative review suggest that perceived stress , childhood adversities , major depressive disorder , educational attainment , physical activity , and sleep duration should also be measured . 0 ###LEFT-WALL### 16 results 0 ###LEFT-WALL### 21 suggest 0 ###LEFT-WALL### 46 . 1 in 2 addition 1 in 14 , 1 in 16 results 2 addition 3 to 3 to 7 factors 4 the 7 factors 5 known 6 individual 6 individual 7 factors 7 factors 8 that 7 factors 9 are 7 factors 11 with 8 that 9 are 9 are 10 associated 11 with 13 length 12 telomere 13 length 15 the 16 results 16 results 17 of 16 results 21 suggest 17 of 20 review 18 the 20 review 19 integrative 20 review 21 suggest 22 that 22 that 39 and 22 that 45 measured 23 perceived 24 stress 24 stress 25 , 25 , 27 adversities 25 , 28 , 26 childhood 27 adversities 28 , 31 disorder 28 , 32 , 29 major 30 depressive 30 depressive 31 disorder 32 , 34 attainment 32 , 35 , 33 educational 34 attainment 35 , 37 activity 35 , 39 and 36 physical 37 activity 38 , 39 and 39 and 41 duration 39 and 42 should 40 sleep 41 duration 42 should 44 be 43 also 44 be 44 be 45 measured discussion : multiple factors have been shown to affect telomere length . 0 ###LEFT-WALL### 1 discussion 0 ###LEFT-WALL### 2 : 2 : 4 factors 2 : 7 shown 2 : 12 . 3 multiple 4 factors 4 factors 5 have 5 have 6 been 6 been 7 shown 7 shown 8 to 8 to 9 affect 9 affect 11 length 10 telomere 11 length to advance understanding of the role of telomere length in health and disease risk , it will be important to further elucidate the mechanisms that contribute to telomere shortening . 0 ###LEFT-WALL### 1 to 0 ###LEFT-WALL### 2 advance 0 ###LEFT-WALL### 15 , 0 ###LEFT-WALL### 30 . 1 to 2 advance 2 advance 3 understanding 2 advance 10 in 3 understanding 4 of 3 understanding 7 of 4 of 6 role 5 the 6 role 7 of 9 length 8 telomere 9 length 10 in 12 and 11 health 12 and 12 and 14 risk 13 disease 14 risk 15 , 16 it 15 , 22 elucidate 16 it 17 will 17 will 18 be 18 be 19 important 19 important 20 to 19 important 22 elucidate 20 to 22 elucidate 21 further 22 elucidate 22 elucidate 24 mechanisms 22 elucidate 27 to 23 the 24 mechanisms 24 mechanisms 25 that 24 mechanisms 26 contribute 25 that 26 contribute 27 to 29 shortening 28 telomere 29 shortening none [background/objectives] : rates of obesity are [greatest] in middle age . 0 ###LEFT-WALL### 1 none 0 ###LEFT-WALL### 3 : 3 : 4 rates 3 : 7 are 3 : 12 . 4 rates 5 of 4 rates 7 are 5 of 6 obesity 7 are 9 in 9 in 11 age 10 middle 11 age obesity is associated with altered activity of brain networks sensing food - related stimuli and internal signals of energy balance , which modulate eating behaviour . 0 ###LEFT-WALL### 1 obesity 0 ###LEFT-WALL### 3 associated 0 ###LEFT-WALL### 26 . 1 obesity 2 is 2 is 3 associated 3 associated 4 with 4 with 6 activity 5 altered 6 activity 6 activity 7 of 7 of 9 networks 8 brain 9 networks 9 networks 10 sensing 9 networks 22 which 9 networks 23 modulate 10 sensing 11 food 11 food 15 and 12 - 15 and 13 related 14 stimuli 14 stimuli 15 and 15 and 17 signals 15 and 18 of 15 and 21 , 16 internal 17 signals 18 of 20 balance 19 energy 20 balance 22 which 23 modulate 23 modulate 25 behaviour 24 eating 25 behaviour the impact of healthy mid - life ageing on these processes has not been characterised . 0 ###LEFT-WALL### 2 impact 0 ###LEFT-WALL### 15 characterised 0 ###LEFT-WALL### 16 . 1 the 2 impact 2 impact 3 of 2 impact 12 has 3 of 8 ageing 4 healthy 7 life 5 mid 6 - 5 mid 7 life 7 life 8 ageing 8 ageing 9 on 9 on 11 processes 10 these 11 processes 12 has 13 not 12 has 14 been 14 been 15 characterised we therefore aimed to investigate changes in brain responses to food cues , and the modulatory effect of meal ingestion on such evoked neural activity , from young adulthood to middle age . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 aimed 1 we 3 aimed 2 therefore 3 aimed 3 aimed 4 to 3 aimed 5 investigate 4 to 5 investigate 5 investigate 6 changes 5 investigate 7 in 5 investigate 21 on 5 investigate 27 from 7 in 9 responses 8 brain 9 responses 9 responses 10 to 9 responses 18 of 10 to 14 and 11 food 12 cues 12 cues 14 and 13 , 14 and 14 and 17 effect 15 the 17 effect 16 modulatory 17 effect 18 of 20 ingestion 19 meal 20 ingestion 21 on 25 activity 22 such 25 activity 23 evoked 25 activity 24 neural 25 activity 26 , 27 from 27 from 29 adulthood 27 from 33 . 28 young 29 adulthood 29 adulthood 30 to 29 adulthood 31 middle 30 to 31 middle 31 middle 32 age subjects/methods : twenty - four healthy , right - handed subjects , aged 19.5 - 52.6 years , were studied on separate days after an overnight fast , randomly receiving 50 ml water or 554 kcal mixed meal before functional brain magnetic resonance imaging while viewing visual food cues . 0 ###LEFT-WALL### 1 subjects/methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 50 . 2 : 8 right 2 : 9 - 3 twenty 4 - 4 - 5 four 4 - 8 right 6 healthy 7 , 6 healthy 8 right 9 - 12 , 10 handed 11 subjects 10 handed 12 , 12 , 18 , 13 aged 17 years 13 aged 18 , 14 19.5 15 - 15 - 16 52.6 15 - 17 years 18 , 19 were 19 were 20 studied 20 studied 21 on 20 studied 24 after 20 studied 39 before 21 on 23 days 22 separate 23 days 24 after 34 or 25 an 26 overnight 25 an 27 fast 26 overnight 27 fast 27 fast 28 , 28 , 33 water 28 , 34 or 29 randomly 30 receiving 30 receiving 33 water 31 50 32 ml 32 ml 33 water 34 or 38 meal 35 554 36 kcal 36 kcal 37 mixed 37 mixed 38 meal 39 before 43 resonance 40 functional 41 brain 41 brain 43 resonance 42 magnetic 43 resonance 43 resonance 44 imaging 44 imaging 45 while 44 imaging 49 cues 45 while 46 viewing 46 viewing 48 food 47 visual 48 food results : across the group , meal ingestion reduced food cue - evoked activity of amygdala , putamen , insula and thalamus , and increased activity in precuneus and bilateral parietal cortex . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 6 , 1 results 2 : 2 : 3 across 3 across 5 group 4 the 5 group 6 , 11 cue 6 , 12 - 7 meal 9 reduced 8 ingestion 9 reduced 9 reduced 11 cue 10 food 11 cue 12 - 24 and 12 - 33 . 13 evoked 14 activity 13 evoked 24 and 14 activity 15 of 15 of 18 putamen 16 amygdala 17 , 16 amygdala 18 putamen 18 putamen 21 and 19 , 21 and 20 insula 21 and 21 and 22 thalamus 21 and 23 , 24 and 25 increased 25 increased 26 activity 25 increased 27 in 27 in 29 and 28 precuneus 29 and 29 and 32 cortex 30 bilateral 32 cortex 31 parietal 32 cortex corrected [for] body mass index , ageing was associated with decreasing food cue - evoked activation of right dorsolateral prefrontal cortex ( dlpfc ) and precuneus , and increasing activation of left ventrolateral prefrontal cortex ( vlpfc ) , bilateral temporal lobe and posterior cingulate in the [fasted] state . 0 ###LEFT-WALL### 5 index 0 ###LEFT-WALL### 6 , 1 corrected 3 body 3 body 5 index 4 mass 5 index 6 , 7 ageing 6 , 9 associated 6 , 14 - 7 ageing 8 was 8 was 9 associated 9 associated 10 with 10 with 13 cue 11 decreasing 12 food 12 food 13 cue 14 - 25 and 15 evoked 16 activation 16 activation 17 of 16 activation 25 and 17 of 21 cortex 18 right 21 cortex 19 dorsolateral 21 cortex 20 prefrontal 21 cortex 21 cortex 23 dlpfc 22 ( 23 dlpfc 23 dlpfc 24 ) 25 and 30 activation 25 and 31 of 26 precuneus 28 and 27 , 28 and 28 and 29 increasing 28 and 30 activation 31 of 35 cortex 32 left 35 cortex 33 ventrolateral 35 cortex 34 prefrontal 35 cortex 35 cortex 37 vlpfc 35 cortex 43 and 36 ( 37 vlpfc 37 vlpfc 38 ) 39 , 43 and 40 bilateral 42 lobe 41 temporal 42 lobe 42 lobe 43 and 43 and 45 cingulate 43 and 50 . 44 posterior 45 cingulate 45 cingulate 46 in 46 in 49 state 47 the 49 state ageing was also positively associated with the difference in food cue - evoked activation between fed and fasted states in the right dlpfc , bilateral amygdala and striatum , [and] negatively associated with that of the left orbitofrontal cortex and vlpfc , superior frontal gyrus , left middle and temporal gyri , posterior cingulate and precuneus . 1 ageing 2 was 2 was 3 also 2 was 5 associated 4 positively 5 associated 5 associated 6 with 6 with 8 difference 7 the 8 difference 8 difference 9 in 8 difference 14 activation 8 difference 19 states 8 difference 20 in 9 in 11 cue 10 food 11 cue 11 cue 13 evoked 12 - 13 evoked 14 activation 15 between 14 activation 19 states 15 between 17 and 16 fed 17 and 17 and 18 fasted 20 in 27 and 21 the 23 dlpfc 22 right 23 dlpfc 23 dlpfc 24 , 24 , 26 amygdala 24 , 27 and 25 bilateral 26 amygdala 27 and 28 striatum 27 and 29 , 27 and 32 associated 27 and 33 with 27 and 35 of 31 negatively 32 associated 33 with 34 that 35 of 40 and 36 the 39 cortex 37 left 39 cortex 38 orbitofrontal 39 cortex 39 cortex 40 and 40 and 41 vlpfc 41 vlpfc 51 gyri 42 , 51 gyri 43 superior 45 gyrus 44 frontal 45 gyrus 45 gyrus 46 , 46 , 48 middle 46 , 49 and 47 left 48 middle 49 and 50 temporal 49 and 51 gyri 51 gyri 55 and 51 gyri 57 . 52 , 55 and 53 posterior 54 cingulate 54 cingulate 55 and 55 and 56 precuneus 55 and 57 . there was an overall tendency towards decreasing modulatory effects of prior meal ingestion on food cue [-] evoked regional brain activity with increasing age . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 was 0 ###LEFT-WALL### 25 . 1 there 2 was 2 was 5 tendency 3 an 4 overall 3 an 5 tendency 4 overall 5 tendency 5 tendency 6 towards 6 towards 7 decreasing 7 decreasing 9 effects 7 decreasing 14 on 7 decreasing 22 with 8 modulatory 9 effects 9 effects 10 of 10 of 13 ingestion 11 prior 13 ingestion 12 meal 13 ingestion 14 on 21 activity 15 food 21 activity 16 cue 18 evoked 18 evoked 20 brain 19 regional 20 brain 20 brain 21 activity 22 with 23 increasing 23 increasing 24 age conclusions : healthy ageing to middle age is associated with diminishing sensitivity to meal ingestion of visual food [cue] - evoked activity in brain regions that represent the salience of food and direct food - associated behaviour . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 20 - 1 conclusions 2 : 2 : 3 healthy 3 healthy 4 ageing 3 healthy 10 with 3 healthy 11 diminishing 4 ageing 5 to 4 ageing 8 is 5 to 7 age 6 middle 7 age 8 is 9 associated 9 associated 10 with 11 diminishing 12 sensitivity 11 diminishing 13 to 13 to 15 ingestion 14 meal 15 ingestion 15 ingestion 16 of 16 of 18 food 17 visual 18 food 20 - 32 and 20 - 35 - 21 evoked 22 activity 21 evoked 23 in 21 evoked 32 and 23 in 25 regions 24 brain 25 regions 25 regions 26 that 25 regions 27 represent 26 that 27 represent 27 represent 29 salience 28 the 29 salience 29 salience 30 of 30 of 31 food 32 and 33 direct 33 direct 34 food 35 - 37 behaviour 35 - 38 . 36 associated 37 behaviour reduced satiety sensing may have a role in the greater risk of obesity in middle age . 0 ###LEFT-WALL### 3 sensing 0 ###LEFT-WALL### 5 have 0 ###LEFT-WALL### 17 . 1 reduced 2 satiety 2 satiety 3 sensing 3 sensing 4 may 4 may 5 have 5 have 7 role 5 have 8 in 5 have 14 in 6 a 7 role 8 in 11 risk 9 the 11 risk 10 greater 11 risk 11 risk 12 of 12 of 13 obesity 14 in 16 age 15 middle 16 age several human mhc [class] ii ( hla ) molecules are strongly associated with high incidence [of] autoimmune diseases including type 1 diabetes ( t1d ) . 0 ###LEFT-WALL### 9 molecules 0 ###LEFT-WALL### 26 . 1 several 9 molecules 2 human 9 molecules 3 mhc 5 ii 3 mhc 7 hla 6 ( 7 hla 7 hla 8 ) 7 hla 9 molecules 9 molecules 10 are 10 are 12 associated 11 strongly 12 associated 12 associated 13 with 13 with 18 diseases 13 with 22 diabetes 14 high 15 incidence 15 incidence 17 autoimmune 17 autoimmune 18 diseases 18 diseases 19 including 19 including 20 type 20 type 21 1 22 diabetes 24 t1d 23 ( 24 t1d 24 t1d 25 ) the hla - humanized mice may thus represent valuable tools to test hla - based vaccines and therapeutics for human autoimmune diseases . 0 ###LEFT-WALL### 2 hla 0 ###LEFT-WALL### 3 - 1 the 2 hla 3 - 5 mice 3 - 8 represent 3 - 14 - 3 - 23 . 4 humanized 5 mice 5 mice 6 may 6 may 8 represent 7 thus 8 represent 8 represent 10 tools 8 represent 11 to 9 valuable 10 tools 11 to 12 test 12 test 13 hla 14 - 17 and 15 based 16 vaccines 15 based 17 and 17 and 18 therapeutics 18 therapeutics 19 for 19 for 22 diseases 20 human 21 autoimmune 21 autoimmune 22 diseases the nod/dr4/b7 [dtg] mice generated by a two [-] step crossing protocol express the hla [-] dr*0401 molecules on 20 % of antigen presenting cells , the human b7 molecules in pancreas , and hla - dr4/gad65 - specific [t] - cells in the blood . 1 the 4 mice 2 nod/dr4/b7 4 mice 4 mice 5 generated 4 mice 6 by 4 mice 13 express 6 by 10 step 7 a 10 step 8 two 10 step 10 step 11 crossing 11 crossing 12 protocol 13 express 18 molecules 13 express 19 on 14 the 18 molecules 15 hla 18 molecules 17 dr*0401 18 molecules 19 on 21 % 20 20 21 % 21 % 22 of 22 of 34 and 23 antigen 24 presenting 23 antigen 34 and 24 presenting 25 cells 25 cells 30 molecules 26 , 30 molecules 27 the 30 molecules 28 human 30 molecules 29 b7 30 molecules 30 molecules 31 in 30 molecules 33 , 31 in 32 pancreas 34 and 35 hla 34 and 37 dr4/gad65 36 - 37 dr4/gad65 37 dr4/gad65 42 cells 37 dr4/gad65 46 . 38 - 42 cells 39 specific 41 - 39 specific 42 cells 42 cells 43 in 42 cells 46 . 43 in 45 blood 44 the 45 blood some 75 % of pre - diabetic nod/dr4/b7 [dtg] mice treated with hu def - gad65 [chimera] remained euglycemic and showed [a] stabilized pancreatic insulitis 6 months after treatment . 0 ###LEFT-WALL### 3 % 0 ###LEFT-WALL### 23 stabilized 0 ###LEFT-WALL### 30 . 1 some 2 75 2 75 3 % 3 % 4 of 3 % 23 stabilized 4 of 16 gad65 5 pre 10 mice 5 pre 16 gad65 6 - 10 mice 7 diabetic 10 mice 8 nod/dr4/b7 10 mice 10 mice 11 treated 10 mice 15 - 11 treated 12 with 12 with 13 hu 12 with 14 def 16 gad65 20 and 18 remained 19 euglycemic 18 remained 20 and 20 and 21 showed 23 stabilized 25 insulitis 23 stabilized 28 after 24 pancreatic 25 insulitis 26 6 27 months 27 months 28 after 28 after 29 treatment the 25 % [non] responders developing hyperglycemia survived 3 - 4 months longer than their untreated littermates . 0 ###LEFT-WALL### 5 responders 0 ###LEFT-WALL### 8 survived 0 ###LEFT-WALL### 18 . 1 the 2 25 2 25 5 responders 3 % 5 responders 5 responders 6 developing 5 responders 8 survived 6 developing 7 hyperglycemia 8 survived 13 longer 9 3 10 - 10 - 11 4 10 - 12 months 12 months 13 longer 13 longer 14 than 14 than 17 littermates 15 their 17 littermates 16 untreated 17 littermates t1d prevention by this reagent occurred by a th2/tr - 1 polarization in the pancreas . 0 ###LEFT-WALL### 2 prevention 0 ###LEFT-WALL### 6 occurred 0 ###LEFT-WALL### 10 - 0 ###LEFT-WALL### 16 . 1 t1d 2 prevention 2 prevention 3 by 2 prevention 6 occurred 3 by 5 reagent 4 this 5 reagent 6 occurred 7 by 7 by 9 th2/tr 8 a 9 th2/tr 10 - 12 polarization 11 1 12 polarization 12 polarization 13 in 13 in 15 pancreas 14 the 15 pancreas this study strongly suggests that the use of soluble phla reagents [to] suppress/stabilize the t1d progression and to extend the life expectancy in the absence of side effects is an efficient and safe therapeutic approach . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 4 suggests 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 36 . 1 this 2 study 2 study 4 suggests 3 strongly 4 suggests 4 suggests 5 that 5 that 7 use 5 that 13 suppress/stabilize 6 the 7 use 7 use 8 of 8 of 11 reagents 9 soluble 11 reagents 10 phla 11 reagents 13 suppress/stabilize 16 progression 14 the 16 progression 15 t1d 16 progression 17 and 18 to 17 and 29 is 18 to 19 extend 18 to 29 is 19 extend 22 expectancy 19 extend 23 in 20 the 22 expectancy 21 life 22 expectancy 23 in 25 absence 24 the 25 absence 25 absence 26 of 26 of 28 effects 27 side 28 effects 29 is 35 approach 30 an 35 approach 31 efficient 32 and 32 and 33 safe 32 and 35 approach 34 therapeutic 35 approach argyrophilic grains are discrete punctate structures that bind to silver stains ; they can be observed within the neuropil of the limbic system , particularly in the elderly . 0 ###LEFT-WALL### 2 grains 0 ###LEFT-WALL### 3 are 0 ###LEFT-WALL### 12 ; 1 argyrophilic 2 grains 2 grains 3 are 3 are 6 structures 4 discrete 5 punctate 5 punctate 6 structures 6 structures 7 that 6 structures 8 bind 7 that 8 bind 8 bind 9 to 9 to 10 silver 10 silver 11 stains 12 ; 13 they 12 ; 16 observed 13 they 14 can 14 can 15 be 15 be 16 observed 16 observed 17 within 16 observed 26 in 17 within 19 neuropil 18 the 19 neuropil 19 neuropil 20 of 20 of 23 system 21 the 23 system 22 limbic 23 system 24 , 25 particularly 24 , 26 in 26 in 28 elderly 26 in 29 . 27 the 28 elderly it has [been] reported that argyrophilic grains are more frequent in patients with corticobasal degeneration ( cbd ) compared with the elderly population in general . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 26 . 1 it 2 has 2 has 4 reported 4 reported 5 that 5 that 7 grains 5 that 8 are 6 argyrophilic 7 grains 7 grains 8 are 8 are 10 frequent 9 more 10 frequent 10 frequent 11 in 10 frequent 20 with 11 in 12 patients 12 patients 13 with 12 patients 19 compared 13 with 15 degeneration 14 corticobasal 15 degeneration 15 degeneration 17 cbd 16 ( 17 cbd 17 cbd 18 ) 20 with 23 population 21 the 23 population 22 elderly 23 population 23 population 25 general 24 in 25 general to determine the frequency and significance of argyrophilic grains in cbd , we examined the temporal lobes from 35 patients with autopsy [-] proven cbd ( mean age , 69.1 years ) and 28 patients with argyrophilic grain disease ( mean age , 95.7 years ) . 0 ###LEFT-WALL### 13 we 0 ###LEFT-WALL### 14 examined 0 ###LEFT-WALL### 47 . 1 to 2 determine 1 to 12 , 1 to 13 we 2 determine 5 and 2 determine 10 in 3 the 4 frequency 4 frequency 5 and 5 and 6 significance 5 and 7 of 7 of 9 grains 8 argyrophilic 9 grains 10 in 11 cbd 13 we 14 examined 14 examined 17 lobes 14 examined 18 from 14 examined 36 with 15 the 17 lobes 16 temporal 17 lobes 18 from 33 and 19 35 20 patients 20 patients 21 with 20 patients 33 and 21 with 25 cbd 22 autopsy 25 cbd 24 proven 25 cbd 25 cbd 28 age 26 ( 28 age 27 mean 28 age 28 age 31 years 28 age 32 ) 29 , 31 years 30 69.1 31 years 31 years 32 ) 33 and 35 patients 34 28 35 patients 36 with 38 grain 36 with 39 disease 37 argyrophilic 38 grain 39 disease 42 age 40 ( 42 age 41 mean 42 age 42 age 45 years 42 age 46 ) 43 , 45 years 44 95.7 45 years 45 years 46 ) grain distributions and densities were evaluated semiquantitatively using gallyas - braak stains and immunohistochemistry with at8 and rd4 antibodies . 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 6 evaluated 0 ###LEFT-WALL### 10 - 1 grain 2 distributions 2 distributions 3 and 3 and 4 densities 3 and 5 were 5 were 6 evaluated 6 evaluated 7 semiquantitatively 6 evaluated 8 using 8 using 9 gallyas 10 - 13 and 10 - 20 . 11 braak 12 stains 12 stains 13 and 13 and 14 immunohistochemistry 13 and 15 with 15 with 17 and 16 at8 17 and 17 and 19 antibodies 18 rd4 19 antibodies argyrophilic grains were observed in all cbd cases ( 100 % ) despite a lower average age at death in this population . 0 ###LEFT-WALL### 2 grains 0 ###LEFT-WALL### 4 observed 0 ###LEFT-WALL### 23 . 1 argyrophilic 2 grains 2 grains 3 were 3 were 4 observed 4 observed 5 in 4 observed 13 despite 4 observed 18 at 4 observed 20 in 5 in 8 cases 6 all 8 cases 7 cbd 8 cases 8 cases 11 % 9 ( 11 % 10 100 11 % 11 % 12 ) 13 despite 17 age 14 a 17 age 15 lower 17 age 16 average 17 age 18 at 19 death 20 in 22 population 21 this 22 population in conclusion , we confirm that argyrophilic grains in cbd are specifically related to the 4 - repeat tau pathology [of] cbd [and] are not simply a result of aging . 0 ###LEFT-WALL### 2 conclusion 0 ###LEFT-WALL### 3 , 0 ###LEFT-WALL### 31 . 1 in 2 conclusion 3 , 4 we 3 , 5 confirm 3 , 17 - 4 we 5 confirm 5 confirm 6 that 6 that 8 grains 6 that 13 related 7 argyrophilic 8 grains 8 grains 9 in 8 grains 11 are 9 in 10 cbd 11 are 12 specifically 11 are 13 related 13 related 14 to 14 to 16 4 15 the 16 4 17 - 22 cbd 17 - 24 are 18 repeat 22 cbd 19 tau 22 cbd 20 pathology 22 cbd 22 cbd 24 are 24 are 25 not 24 are 26 simply 24 are 28 result 27 a 28 result 28 result 29 of 29 of 30 aging [an] in vitro [and] in vivo study was performed to quantify adhesion and biofilm formation ability [of] pseudomonas aeruginosa slime producer under the effect [of] sub - minimal inhibitory concentrations ( mics ) of pexiganan and imipenem . 0 ###LEFT-WALL### 7 study 0 ###LEFT-WALL### 9 performed 0 ###LEFT-WALL### 38 . 2 in 3 vitro 3 vitro 7 study 5 in 6 vivo 6 vivo 7 study 7 study 8 was 8 was 9 performed 9 performed 10 to 9 performed 22 under 10 to 11 quantify 11 quantify 13 and 12 adhesion 13 and 13 and 21 producer 14 biofilm 19 aeruginosa 15 formation 16 ability 16 ability 19 aeruginosa 18 pseudomonas 19 aeruginosa 19 aeruginosa 21 producer 20 slime 21 producer 22 under 26 sub 23 the 26 sub 24 effect 26 sub 26 sub 30 concentrations 26 sub 34 of 27 - 30 concentrations 28 minimal 30 concentrations 29 inhibitory 30 concentrations 30 concentrations 32 mics 30 concentrations 33 ) 31 ( 32 mics 32 mics 33 ) 34 of 36 and 35 pexiganan 36 and 36 and 37 imipenem to evaluate adherence [,] squares of ureteral stents were placed in six - well tissue - culture plates containing 6 ml of [a] cell suspension grown in the presence [of] sub - mics of study antibiotics . 0 ###LEFT-WALL### 1 to 0 ###LEFT-WALL### 2 evaluate 0 ###LEFT-WALL### 32 - 0 ###LEFT-WALL### 37 . 1 to 2 evaluate 2 evaluate 5 squares 2 evaluate 10 placed 3 adherence 5 squares 5 squares 6 of 5 squares 9 were 6 of 8 stents 7 ureteral 8 stents 9 were 10 placed 10 placed 11 in 11 in 12 six 12 six 15 tissue 13 - 15 tissue 14 well 15 tissue 15 tissue 18 plates 15 tissue 32 - 16 - 18 plates 17 culture 18 plates 18 plates 19 containing 18 plates 22 of 18 plates 26 grown 18 plates 32 - 19 containing 21 ml 20 6 21 ml 22 of 25 suspension 24 cell 25 suspension 26 grown 27 in 27 in 31 sub 28 the 31 sub 29 presence 31 sub 32 - 33 mics 33 mics 34 of 34 of 36 antibiotics 35 study 36 antibiotics to evaluate biofilm formation sterilized squares were placed in six - well tissue culture plates containing 6 ml of triptic soy broth ( tsb ) supplemented with 0.25 % of glucose and the respective amount [of] antibiotic . 0 ###LEFT-WALL### 1 to 0 ###LEFT-WALL### 2 evaluate 0 ###LEFT-WALL### 11 - 0 ###LEFT-WALL### 26 supplemented 0 ###LEFT-WALL### 38 . 1 to 2 evaluate 2 evaluate 6 squares 2 evaluate 8 placed 3 biofilm 4 formation 4 formation 5 sterilized 5 sterilized 6 squares 6 squares 7 were 7 were 8 placed 8 placed 9 in 9 in 10 six 11 - 12 well 12 well 15 plates 13 tissue 14 culture 14 culture 15 plates 15 plates 16 containing 15 plates 26 supplemented 16 containing 18 ml 16 containing 26 supplemented 17 6 18 ml 18 ml 19 of 19 of 22 broth 20 triptic 21 soy 21 soy 22 broth 22 broth 24 tsb 23 ( 24 tsb 24 tsb 25 ) 26 supplemented 27 with 27 with 29 % 27 with 37 antibiotic 28 0.25 29 % 29 % 30 of 30 of 32 and 31 glucose 32 and 32 and 35 amount 33 the 35 amount 34 respective 35 amount for in vivo study a biofilm infection rat model was performed . 0 ###LEFT-WALL### 1 for 0 ###LEFT-WALL### 11 performed 0 ###LEFT-WALL### 12 . 1 for 4 study 2 in 3 vivo 3 vivo 4 study 4 study 9 model 4 study 10 was 4 study 11 performed 5 a 6 biofilm 5 a 9 model 6 biofilm 7 infection 7 infection 9 model 8 rat 9 model 9 model 10 was the study included an uninfected control group to evaluate the sterility of surgical procedure , a group infected with a slime [-] producer p . aeruginosa strain not previously treated with antibiotics and two groups infected with the strain previously treated with imipenem or pexiganan . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 included 0 ###LEFT-WALL### 25 . 1 the 2 study 2 study 3 included 3 included 7 group 3 included 8 to 3 included 19 with 4 an 7 group 5 uninfected 6 control 6 control 7 group 8 to 9 evaluate 9 evaluate 11 sterility 10 the 11 sterility 11 sterility 12 of 11 sterility 18 infected 12 of 14 procedure 13 surgical 14 procedure 15 , 18 infected 16 a 17 group 17 group 18 infected 19 with 23 producer 19 with 24 p 20 a 23 producer 21 slime 23 producer 25 . 44 or 25 . 46 . 26 aeruginosa 27 strain 27 strain 28 not 27 strain 33 and 28 not 30 treated 29 previously 30 treated 30 treated 31 with 31 with 32 antibiotics 33 and 35 groups 33 and 41 treated 33 and 44 or 34 two 35 groups 35 groups 36 infected 36 infected 37 with 37 with 39 strain 38 the 39 strain 40 previously 41 treated 41 treated 42 with 42 with 43 imipenem 44 or 45 pexiganan adherence and [biofilm] in vitro formation was strongly affected by pre - treatment with pexiganan and imipenem , with the latter being the more effective antibiotic . 0 ###LEFT-WALL### 1 adherence 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 27 . 2 and 6 formation 2 and 9 affected 4 in 5 vitro 5 vitro 6 formation 6 formation 7 was 7 was 8 strongly 7 was 9 affected 9 affected 10 by 9 affected 19 with 10 by 11 pre 11 pre 13 treatment 12 - 13 treatment 13 treatment 14 with 13 treatment 18 , 14 with 16 and 15 pexiganan 16 and 16 and 17 imipenem 19 with 21 latter 19 with 22 being 20 the 21 latter 22 being 26 antibiotic 23 the 26 antibiotic 24 more 25 effective 25 effective 26 antibiotic [the] in vivo results showed a reduction [in] bacterial load on the ureteral stent tissue of the pre - treated strain . 0 ###LEFT-WALL### 4 results 0 ###LEFT-WALL### 5 showed 0 ###LEFT-WALL### 22 . 2 in 3 vivo 3 vivo 4 results 4 results 5 showed 5 showed 10 load 5 showed 11 on 6 a 7 reduction 6 a 10 load 7 reduction 10 load 9 bacterial 10 load 11 on 15 tissue 12 the 15 tissue 13 ureteral 14 stent 14 stent 15 tissue 15 tissue 16 of 16 of 21 strain 17 the 21 strain 18 pre 19 - 18 pre 21 strain 20 treated 21 strain differently , urine cultures showed no differences in bacterial growth for the pre - treated strain showing that it retained its ability to cause infection . 0 ###LEFT-WALL### 4 cultures 0 ###LEFT-WALL### 5 showed 0 ###LEFT-WALL### 26 . 1 differently 2 , 1 differently 4 cultures 3 urine 4 cultures 4 cultures 5 showed 5 showed 7 differences 5 showed 25 infection 6 no 7 differences 7 differences 8 in 8 in 10 growth 9 bacterial 10 growth 10 growth 11 for 10 growth 18 that 10 growth 23 to 11 for 17 showing 12 the 17 showing 13 pre 14 - 13 pre 16 strain 15 treated 16 strain 16 strain 17 showing 18 that 19 it 18 that 20 retained 19 it 20 retained 20 retained 22 ability 20 retained 23 to 21 its 22 ability 24 cause 25 infection this study suggests that sub - mic imipenem and pexiganan could be a good strategy to target the adhesion process during the infection cycle . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 suggests 0 ###LEFT-WALL### 6 - 1 this 2 study 2 study 3 suggests 3 suggests 5 sub 4 that 5 sub 6 - 9 and 6 - 12 be 6 - 25 . 7 mic 8 imipenem 8 imipenem 9 and 9 and 10 pexiganan 9 and 11 could 11 could 12 be 12 be 15 strategy 12 be 16 to 13 a 14 good 13 a 15 strategy 14 good 15 strategy 16 to 17 target 17 target 20 process 17 target 21 during 18 the 20 process 19 adhesion 20 process 21 during 24 cycle 22 the 24 cycle 23 infection 24 cycle meinzer [et] [al] . 0 ###LEFT-WALL### 1 meinzer 0 ###LEFT-WALL### 4 . ( [j] neurosci 33 : 12470 - 12478 , 2013 ) have recently reported that anodal transcranial direct current stimulation ( atdcs ) mitigates age - related cognitive changes . 0 ###LEFT-WALL### 4 33 0 ###LEFT-WALL### 5 : 0 ###LEFT-WALL### 7 - 1 ( 3 neurosci 3 neurosci 4 33 4 33 5 : 5 : 6 12470 7 - 8 12478 7 - 14 reported 7 - 27 related 8 12478 10 2013 8 12478 12 have 9 , 10 2013 10 2013 11 ) 12 have 14 reported 13 recently 14 reported 14 reported 15 that 15 that 20 stimulation 15 that 24 mitigates 16 anodal 19 current 17 transcranial 19 current 18 direct 19 current 19 current 20 stimulation 20 stimulation 22 atdcs 20 stimulation 24 mitigates 21 ( 22 atdcs 22 atdcs 23 ) 24 mitigates 25 age 26 - 27 related 27 related 29 changes 27 related 30 . 28 cognitive 29 changes simultaneous measurement of bold [signal] during atdcs also showed " youth - like " processing in an elderly population . 0 ###LEFT-WALL### 2 measurement 0 ###LEFT-WALL### 9 showed 0 ###LEFT-WALL### 12 - 1 simultaneous 2 measurement 2 measurement 3 of 2 measurement 9 showed 3 of 4 bold 4 bold 6 during 6 during 7 atdcs 8 also 9 showed 9 showed 10 " 9 showed 11 youth 12 - 13 like 12 - 20 . 13 like 14 " 13 like 15 processing 13 like 16 in 16 in 19 population 17 an 18 elderly 17 an 19 population 18 elderly 19 population although the effects are very promising , the underlying mechanisms of atdcs are still not clear . 0 ###LEFT-WALL### 10 mechanisms 0 ###LEFT-WALL### 13 are 0 ###LEFT-WALL### 17 . 1 although 3 effects 1 although 4 are 1 although 7 , 1 although 10 mechanisms 2 the 3 effects 3 effects 4 are 4 are 6 promising 5 very 6 promising 8 the 10 mechanisms 9 underlying 10 mechanisms 10 mechanisms 11 of 10 mechanisms 13 are 11 of 12 atdcs 13 are 14 still 13 are 15 not 13 are 16 clear in this article , we provide a critical review of the results , emphasizing the article 's significance and providing additional insight that will help elucidate the results and atdcs mechanisms . 0 ###LEFT-WALL### 5 we 0 ###LEFT-WALL### 6 provide 0 ###LEFT-WALL### 13 , 0 ###LEFT-WALL### 17 's 0 ###LEFT-WALL### 32 . 1 in 3 article 1 in 4 , 1 in 5 we 2 this 3 article 5 we 6 provide 6 provide 9 review 7 a 8 critical 7 a 9 review 8 critical 9 review 9 review 10 of 10 of 12 results 11 the 12 results 13 , 14 emphasizing 13 , 17 's 14 emphasizing 16 article 14 emphasizing 17 's 15 the 16 article 17 's 29 and 18 significance 19 and 19 and 22 insight 19 and 23 that 19 and 24 will 19 and 29 and 20 providing 22 insight 21 additional 22 insight 23 that 24 will 24 will 25 help 25 help 26 elucidate 26 elucidate 28 results 27 the 28 results 29 and 31 mechanisms 30 atdcs 31 mechanisms background : recent studies have shown that vitamin d status may be relevant for physical and cognitive performance in the older population . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 6 shown 0 ###LEFT-WALL### 23 . 2 : 3 recent 3 recent 4 studies 3 recent 6 shown 4 studies 5 have 5 have 6 shown 6 shown 7 that 7 that 10 status 7 that 12 be 8 vitamin 9 d 8 vitamin 10 status 10 status 11 may 11 may 12 be 12 be 13 relevant 13 relevant 14 for 14 for 18 performance 15 physical 16 and 16 and 17 cognitive 16 and 18 performance 18 performance 19 in 19 in 22 population 20 the 22 population 21 older 22 population this association may be of particular interest to older people at risk for cognitive impairment and functional decline . 0 ###LEFT-WALL### 2 association 0 ###LEFT-WALL### 4 be 0 ###LEFT-WALL### 19 . 1 this 2 association 2 association 3 may 3 may 4 be 4 be 5 of 4 be 8 to 4 be 11 at 5 of 7 interest 6 particular 7 interest 8 to 10 people 9 older 10 people 11 at 16 and 12 risk 13 for 12 risk 16 and 13 for 15 impairment 14 cognitive 15 impairment 16 and 18 decline 17 functional 18 decline objective : the aim of this study was to determine the association between serum 25 - hydroxyvitamin d [ 25 ( oh )d ] status and functional mobility in seniors assessed in a memory clinic . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 10 determine 2 : 4 aim 3 the 4 aim 4 aim 5 of 4 aim 7 study 4 aim 10 determine 5 of 6 this 7 study 8 was 8 was 9 to 8 was 10 determine 9 to 10 determine 10 determine 12 association 10 determine 13 between 11 the 12 association 13 between 14 serum 14 serum 15 25 14 serum 17 hydroxyvitamin 16 - 17 hydroxyvitamin 17 hydroxyvitamin 18 d 17 hydroxyvitamin 26 and 17 hydroxyvitamin 36 . 19 [ 26 and 20 25 22 oh 21 ( 22 oh 22 oh 23 )d 22 oh 24 ] 22 oh 25 status 25 status 26 and 26 and 28 mobility 26 and 29 in 26 and 31 assessed 26 and 36 . 27 functional 28 mobility 29 in 30 seniors 31 assessed 32 in 32 in 35 clinic 33 a 35 clinic 34 memory 35 clinic methods : we conducted a cross - sectional study of outpatients ( n = 404 ) in a memory clinic . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 3 we 2 : 4 conducted 2 : 21 . 3 we 4 conducted 4 conducted 6 cross 4 conducted 17 in 5 a 6 cross 6 cross 9 study 7 - 9 study 8 sectional 9 study 9 study 10 of 9 study 16 ) 10 of 11 outpatients 11 outpatients 14 = 12 ( 14 = 13 n 14 = 14 = 15 404 17 in 20 clinic 18 a 19 memory 18 a 20 clinic 19 memory 20 clinic functional mobility was assessed with three endpoints : normal and fast walking speed and the timed up and go ( tug ) test . 0 ###LEFT-WALL### 2 mobility 0 ###LEFT-WALL### 4 assessed 0 ###LEFT-WALL### 8 : 0 ###LEFT-WALL### 24 . 1 functional 2 mobility 2 mobility 3 was 3 was 4 assessed 4 assessed 5 with 5 with 7 endpoints 6 three 7 endpoints 8 : 18 and 9 normal 10 and 10 and 11 fast 10 and 12 walking 10 and 14 and 12 walking 13 speed 14 and 17 up 14 and 18 and 15 the 17 up 16 timed 17 up 18 and 23 test 19 go 21 tug 20 ( 21 tug 21 tug 22 ) 21 tug 23 test adjusted multivariate analyses in all patients and two pre - planned subgroup analyses in vulnerable seniors ( previous fall and mmse score of ≥26 or no previous fall and mmse score of < 26 ) versus less vulnerable seniors ( no previous fall and mmse score of ≥26 ) were performed to assess the association of 25 ( oh )d and functional mobility . 0 ###LEFT-WALL### 7 and 0 ###LEFT-WALL### 64 . 1 adjusted 3 analyses 1 adjusted 4 in 1 adjusted 7 and 2 multivariate 3 analyses 4 in 6 patients 5 all 6 patients 7 and 53 assess 8 two 13 analyses 9 pre 10 - 9 pre 13 analyses 11 planned 12 subgroup 12 subgroup 13 analyses 13 analyses 14 in 13 analyses 25 or 13 analyses 50 were 14 in 16 seniors 15 vulnerable 16 seniors 17 ( 25 or 18 previous 19 fall 19 fall 20 and 20 and 22 score 20 and 23 of 20 and 25 or 21 mmse 22 score 23 of 24 ≥26 25 or 31 score 25 or 35 ) 25 or 36 versus 25 or 49 ) 26 no 31 score 27 previous 28 fall 28 fall 29 and 29 and 30 mmse 29 and 31 score 31 score 32 of 32 of 34 26 33 < 34 26 36 versus 39 seniors 37 less 38 vulnerable 38 vulnerable 39 seniors 39 seniors 44 and 40 ( 44 and 41 no 43 fall 42 previous 43 fall 43 fall 44 and 44 and 46 score 44 and 47 of 44 and 49 ) 45 mmse 46 score 47 of 48 ≥26 50 were 51 performed 51 performed 52 to 52 to 53 assess 53 assess 61 and 54 the 55 association 55 association 56 of 55 association 61 and 56 of 59 oh 57 25 59 oh 58 ( 59 oh 59 oh 60 )d 61 and 63 mobility 62 functional 63 mobility seniors in the lowest 25 ( oh )d quartile ( < 39 nmol/l ) had significantly worse functional mobility compared to the highest 25 ( oh )d quartile ( [>81] [nmol/l] [ )( adjusted for all covariates [,] seniors in the highest quartile performed 9.4 % better in normal ( p = 0.02 [ )(and 9.2 % better in fast ( p = 0.004 ) walking speed , [and] 4.4 % better in the tug test ( p = 0.24 ) . 1 seniors 9 quartile 2 in 4 lowest 2 in 9 quartile 3 the 4 lowest 5 25 7 oh 6 ( 7 oh 7 oh 8 )d 7 oh 9 quartile 9 quartile 13 nmol/l 9 quartile 15 had 10 ( 13 nmol/l 11 < 12 39 12 39 13 nmol/l 13 nmol/l 14 ) 15 had 19 mobility 15 had 20 compared 16 significantly 17 worse 17 worse 19 mobility 18 functional 19 mobility 20 compared 21 to 21 to 28 quartile 22 the 23 highest 22 the 28 quartile 24 25 26 oh 25 ( 26 oh 26 oh 27 )d 26 oh 28 quartile 28 quartile 34 adjusted 29 ( 34 adjusted 34 adjusted 35 for 34 adjusted 40 in 35 for 39 seniors 36 all 39 seniors 37 covariates 39 seniors 40 in 42 highest 41 the 42 highest 42 highest 43 quartile 42 highest 48 in 42 highest 49 normal 43 quartile 44 performed 44 performed 46 % 44 performed 47 better 44 performed 48 in 45 9.4 46 % 49 normal 52 = 50 ( 52 = 51 p 52 = 52 = 55 )(and 53 0.02 55 )(and 55 )(and 56 9.2 55 )(and 57 % 55 )(and 58 better 55 )(and 66 walking 56 9.2 57 % 57 % 58 better 58 better 59 in 59 in 60 fast 60 fast 63 = 61 ( 63 = 62 p 63 = 63 = 64 0.004 63 = 65 ) 66 walking 67 speed 67 speed 71 % 68 , 71 % 70 4.4 71 % 71 % 72 better 71 % 79 = 71 % 82 . 72 better 73 in 73 in 76 test 74 the 76 test 75 tug 76 test 77 ( 79 = 78 p 79 = 79 = 80 0.24 79 = 81 ) the association between 25 ( oh )d status and functional mobility was most pronounced in less vulnerable seniors ( [p] [for] [trend] significant for all three mobility tests ) . 0 ###LEFT-WALL### 2 association 0 ###LEFT-WALL### 12 was 0 ###LEFT-WALL### 30 . 1 the 2 association 2 association 3 between 2 association 12 was 3 between 9 and 4 25 6 oh 5 ( 6 oh 6 oh 7 )d 6 oh 8 status 8 status 9 and 9 and 11 mobility 10 functional 11 mobility 12 was 13 most 13 most 14 pronounced 13 most 15 in 13 most 23 significant 15 in 18 seniors 16 less 17 vulnerable 17 vulnerable 18 seniors 19 ( 23 significant 23 significant 24 for 23 significant 29 ) 24 for 28 tests 25 all 26 three 26 three 28 tests 27 mobility 28 tests seniors with a higher 25 ( oh )d status also had better cognitive function [(] mmse score [;] p = 0.006 ) . 0 ###LEFT-WALL### 1 seniors 0 ###LEFT-WALL### 17 score 0 ###LEFT-WALL### 23 . 1 seniors 2 with 1 seniors 9 status 1 seniors 11 had 1 seniors 17 score 2 with 7 oh 3 a 7 oh 4 higher 7 oh 5 25 7 oh 6 ( 7 oh 7 oh 8 )d 9 status 11 had 10 also 11 had 11 had 12 better 12 better 16 mmse 13 cognitive 14 function 14 function 16 mmse 17 score 20 = 19 p 20 = 20 = 21 0.006 20 = 22 ) conclusions : lower serum 25 ( oh )d status is associated with poorer functional mobility and cognitive function , therefore supporting 25 ( oh )d assessment in this population at risk for both functional and cognitive decline . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 9 status 2 : 11 associated 2 : 38 . 3 lower 4 serum 4 serum 9 status 5 25 7 oh 6 ( 7 oh 7 oh 8 )d 7 oh 9 status 9 status 10 is 10 is 11 associated 11 associated 12 with 12 with 26 assessment 13 poorer 15 mobility 14 functional 15 mobility 15 mobility 16 and 16 and 18 function 16 and 19 , 16 and 21 supporting 16 and 26 assessment 17 cognitive 18 function 20 therefore 21 supporting 21 supporting 24 oh 22 25 24 oh 23 ( 24 oh 24 oh 25 )d 26 assessment 27 in 26 assessment 30 at 27 in 29 population 28 this 29 population 30 at 31 risk 31 risk 32 for 32 for 35 and 33 both 35 and 34 functional 35 and 35 and 37 decline 36 cognitive 37 decline tumor angiogenesis [is] mainly mediated by vascular endothelial growth [factor] ( vegf ) , a pro - angiogenic factor produced by cancer cells and active on the endothelium through the vegf receptor 2 ( vegfr - 2 ) . 0 ###LEFT-WALL### 2 angiogenesis 0 ###LEFT-WALL### 19 factor 0 ###LEFT-WALL### 39 . 1 tumor 2 angiogenesis 2 angiogenesis 5 mediated 2 angiogenesis 19 factor 4 mainly 5 mediated 5 mediated 6 by 5 mediated 18 angiogenic 6 by 9 growth 7 vascular 9 growth 8 endothelial 9 growth 9 growth 12 vegf 9 growth 16 pro 11 ( 12 vegf 12 vegf 13 ) 14 , 16 pro 15 a 16 pro 16 pro 17 - 19 factor 20 produced 19 factor 21 by 19 factor 26 on 21 by 24 and 22 cancer 23 cells 23 cells 24 and 24 and 25 active 26 on 28 endothelium 27 the 28 endothelium 28 endothelium 29 through 28 endothelium 35 vegfr 29 through 32 receptor 30 the 32 receptor 31 vegf 32 receptor 32 receptor 33 2 34 ( 35 vegfr 35 vegfr 37 2 35 vegfr 38 ) 36 - 37 2 37 2 38 ) here we identify a [g] [-] rich sequence within the proximal promoter region of vegfr - 2 , able to form an antiparallel [g] - quadruplex ( g4 ) structure . 0 ###LEFT-WALL### 2 we 0 ###LEFT-WALL### 3 identify 0 ###LEFT-WALL### 31 . 1 here 2 we 2 we 3 identify 3 identify 8 sequence 3 identify 9 within 4 a 8 sequence 7 rich 8 sequence 9 within 13 region 10 the 13 region 11 proximal 12 promoter 12 promoter 13 region 13 region 14 of 14 of 30 structure 15 vegfr 17 2 15 vegfr 30 structure 16 - 17 2 17 2 19 able 17 2 29 ) 18 , 19 able 19 able 20 to 19 able 21 form 19 able 29 ) 20 to 21 form 21 form 23 antiparallel 22 an 23 antiparallel 23 antiparallel 26 quadruplex 25 - 26 quadruplex 26 quadruplex 28 g4 26 quadruplex 29 ) 27 ( 28 g4 28 g4 29 ) this g4 structure can be efficiently stabilized by small molecules with the consequent inhibition of vegfr - 2 expression . 0 ###LEFT-WALL### 3 structure 0 ###LEFT-WALL### 7 stabilized 0 ###LEFT-WALL### 17 - 1 this 3 structure 2 g4 3 structure 3 structure 4 can 4 can 5 be 5 be 6 efficiently 5 be 7 stabilized 7 stabilized 8 by 7 stabilized 11 with 8 by 10 molecules 9 small 10 molecules 11 with 14 inhibition 12 the 14 inhibition 13 consequent 14 inhibition 14 inhibition 15 of 15 of 16 vegfr 17 - 19 expression 17 - 20 . 18 2 19 expression functionally , the g4 - mediated reduction of vegfr - 2 protein causes [a] switching off of signaling components that , converging on actin [cytoskeleton] , regulate the cellular events leading to endothelial cell proliferation [,] migration and differentiation . 0 ###LEFT-WALL### 13 causes 0 ###LEFT-WALL### 27 regulate 0 ###LEFT-WALL### 40 . 1 functionally 2 , 1 functionally 13 causes 3 the 13 causes 4 g4 7 reduction 4 g4 13 causes 5 - 7 reduction 6 mediated 7 reduction 7 reduction 8 of 7 reduction 10 - 8 of 9 vegfr 11 2 12 protein 12 protein 13 causes 13 causes 15 switching 13 causes 27 regulate 15 switching 17 of 15 switching 20 that 15 switching 22 converging 16 off 17 of 17 of 19 components 18 signaling 19 components 21 , 22 converging 22 converging 23 on 22 converging 26 , 23 on 24 actin 27 regulate 30 events 27 regulate 32 to 28 the 30 events 29 cellular 30 events 30 events 31 leading 32 to 38 and 33 endothelial 34 cell 34 cell 37 migration 35 proliferation 37 migration 37 migration 38 and 38 and 39 differentiation as a result of endothelial cell function impairment , angiogenic process [is] strongly inhibited by g4 ligands both in vitro and in vivo . 0 ###LEFT-WALL### 11 process 0 ###LEFT-WALL### 17 ligands 0 ###LEFT-WALL### 24 . 1 as 3 result 1 as 9 , 1 as 11 process 2 a 3 result 3 result 4 of 4 of 8 impairment 5 endothelial 6 cell 6 cell 8 impairment 7 function 8 impairment 10 angiogenic 11 process 11 process 14 inhibited 11 process 17 ligands 13 strongly 14 inhibited 14 inhibited 15 by 15 by 16 g4 17 ligands 18 both 17 ligands 21 and 19 in 20 vitro 20 vitro 21 and 21 and 23 vivo 22 in 23 vivo interestingly , the g4 [-] mediated antiangiogenic effect seems to recapitulate that observed by using a specific interference rna against vegfr - 2 , and it is strongly antagonized by overexpressing the vegfr - 2 gene . 0 ###LEFT-WALL### 8 effect 0 ###LEFT-WALL### 9 seems 0 ###LEFT-WALL### 13 observed 0 ###LEFT-WALL### 25 and 0 ###LEFT-WALL### 37 . 1 interestingly 2 , 1 interestingly 8 effect 3 the 8 effect 4 g4 6 mediated 6 mediated 8 effect 7 antiangiogenic 8 effect 8 effect 9 seems 9 seems 10 to 9 seems 13 observed 10 to 11 recapitulate 12 that 13 observed 13 observed 14 by 13 observed 20 against 14 by 15 using 15 using 19 rna 16 a 17 specific 16 a 19 rna 17 specific 18 interference 18 interference 19 rna 20 against 21 vegfr 21 vegfr 23 2 22 - 23 2 23 2 24 , 24 , 25 and 25 and 26 it 25 and 29 antagonized 26 it 27 is 27 is 29 antagonized 28 strongly 29 antagonized 29 antagonized 30 by 30 by 31 overexpressing 31 overexpressing 36 gene 32 the 36 gene 33 vegfr 34 - 33 vegfr 36 gene 35 2 36 gene when considering the burden of visual impairment on aging individuals and society at large , it is important to bear in mind that vision changes are a natural aspect of aging . 0 ###LEFT-WALL### 16 it 0 ###LEFT-WALL### 20 bear 0 ###LEFT-WALL### 32 . 1 when 2 considering 1 when 15 , 1 when 16 it 2 considering 4 burden 2 considering 11 and 3 the 4 burden 4 burden 5 of 4 burden 8 on 5 of 7 impairment 6 visual 7 impairment 8 on 9 aging 10 individuals 11 and 11 and 12 society 12 society 14 large 13 at 14 large 16 it 17 is 17 is 18 important 18 important 19 to 18 important 20 bear 19 to 20 bear 20 bear 21 in 21 in 22 mind 22 mind 23 that 22 mind 31 aging 23 that 25 changes 23 that 26 are 24 vision 25 changes 25 changes 26 are 26 are 29 aspect 27 a 29 aspect 28 natural 29 aspect 29 aspect 30 of 30 of 31 aging in this article , we consider vision changes that are part of normal aging , the prevalence of abnormal vision changes caused by disorders of the visual system , and the anticipated incidence and impact of visual impairment as the us population ages . 0 ###LEFT-WALL### 5 we 0 ###LEFT-WALL### 6 consider 0 ###LEFT-WALL### 44 . 1 in 3 article 1 in 4 , 1 in 5 we 2 this 3 article 5 we 6 consider 6 consider 7 vision 6 consider 8 changes 6 consider 39 as 8 changes 9 that 8 changes 10 are 9 that 10 are 10 are 34 and 11 part 12 of 11 part 15 , 12 of 14 aging 13 normal 14 aging 15 , 17 prevalence 15 , 30 and 16 the 17 prevalence 17 prevalence 18 of 18 of 21 changes 19 abnormal 20 vision 20 vision 21 changes 21 changes 22 caused 21 changes 25 of 22 caused 23 by 23 by 24 disorders 25 of 28 system 26 the 28 system 27 visual 28 system 29 , 30 and 30 and 33 incidence 30 and 34 and 31 the 33 incidence 32 anticipated 33 incidence 34 and 35 impact 34 and 36 of 36 of 38 impairment 37 visual 38 impairment 39 as 43 ages 40 the 43 ages 41 us 42 population 42 population 43 ages we then discuss the services available to reduce the impact of vision loss , and the extent to which those services can and should be improved , not only to be better prepared for the anticipated increase in low vision over the coming decades , but also to increase the awareness of interactions between visual impairment and comorbidities that are common among the elderly . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 discuss 0 ###LEFT-WALL### 65 . 1 we 3 discuss 2 then 3 discuss 3 discuss 5 services 3 discuss 7 to 4 the 5 services 5 services 6 available 7 to 23 and 8 reduce 15 and 8 reduce 23 and 9 the 10 impact 10 impact 11 of 10 impact 15 and 11 of 13 loss 12 vision 13 loss 14 , 15 and 15 and 17 extent 15 and 18 to 16 the 17 extent 18 to 19 which 18 to 21 services 18 to 22 can 20 those 21 services 21 services 22 can 23 and 24 should 24 should 25 be 25 be 26 improved 26 improved 30 to 26 improved 46 but 27 , 30 to 28 not 30 to 29 only 30 to 30 to 31 be 30 to 45 , 31 be 33 prepared 32 better 33 prepared 33 prepared 34 for 33 prepared 38 in 33 prepared 41 over 34 for 37 increase 35 the 37 increase 36 anticipated 37 increase 38 in 40 vision 39 low 40 vision 41 over 44 decades 42 the 44 decades 43 coming 44 decades 46 but 48 to 46 but 49 increase 47 also 48 to 48 to 49 increase 49 increase 51 awareness 49 increase 54 between 49 increase 62 among 50 the 51 awareness 51 awareness 52 of 52 of 53 interactions 54 between 57 and 55 visual 56 impairment 56 impairment 57 and 57 and 58 comorbidities 57 and 59 that 57 and 60 are 59 that 60 are 60 are 61 common 62 among 64 elderly 63 the 64 elderly finally , we consider [how] to promote improved quality , availability , and acceptance of low vision care to lessen the impact of visual impairment on individuals , and its burden on society . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 consider 0 ###LEFT-WALL### 34 . 1 finally 2 , 1 finally 3 we 3 we 4 consider 4 consider 6 to 4 consider 29 and 4 consider 32 on 6 to 10 , 7 promote 9 quality 7 promote 10 , 8 improved 9 quality 10 , 20 lessen 11 availability 13 and 12 , 13 and 13 and 14 acceptance 13 and 15 of 13 and 18 care 15 of 17 vision 16 low 17 vision 18 care 19 to 19 to 20 lessen 21 the 22 impact 22 impact 23 of 22 impact 29 and 23 of 25 impairment 24 visual 25 impairment 25 impairment 26 on 26 on 27 individuals 28 , 29 and 29 and 31 burden 30 its 31 burden 32 on 33 society none reduced quality of life and financial burden due to visual impairment and blindness begin to increase dramatically when individuals reach the age of 40 . 0 ###LEFT-WALL### 1 none 0 ###LEFT-WALL### 17 increase 0 ###LEFT-WALL### 26 . 1 none 6 and 1 none 16 to 1 none 17 increase 2 reduced 3 quality 3 quality 4 of 3 quality 6 and 4 of 5 life 6 and 8 burden 6 and 9 due 6 and 15 begin 7 financial 8 burden 9 due 10 to 10 to 13 and 11 visual 12 impairment 12 impairment 13 and 13 and 14 blindness 15 begin 16 to 17 increase 18 dramatically 17 increase 19 when 19 when 20 individuals 19 when 21 reach 20 individuals 21 reach 21 reach 23 age 22 the 23 age 23 age 24 of 24 of 25 40 the major causes of age - related vision loss can be traced to changes to the structure and function of the lens , one of the tissues responsible for focusing light on the retina . 0 ###LEFT-WALL### 3 causes 0 ###LEFT-WALL### 12 traced 1 the 3 causes 2 major 3 causes 3 causes 4 of 3 causes 10 can 4 of 5 age 6 - 7 related 7 related 9 loss 7 related 10 can 8 vision 9 loss 10 can 11 be 11 be 12 traced 12 traced 13 to 12 traced 15 to 13 to 14 changes 15 to 18 and 16 the 17 structure 17 structure 18 and 18 and 19 function 18 and 20 of 20 of 22 lens 21 the 22 lens 22 lens 24 one 23 , 24 one 24 one 25 of 24 one 28 responsible 24 one 31 light 24 one 35 . 25 of 27 tissues 26 the 27 tissues 28 responsible 29 for 29 for 30 focusing 31 light 32 on 32 on 34 retina 33 the 34 retina age - related nuclear cataracts , which are caused by aggregation and condensation of proteins , diminish vision because they impede the transmission and focusing of light on the retina . 0 ###LEFT-WALL### 1 age 0 ###LEFT-WALL### 3 related 0 ###LEFT-WALL### 6 , 0 ###LEFT-WALL### 31 . 2 - 3 related 3 related 5 cataracts 3 related 6 , 4 nuclear 5 cataracts 6 , 7 which 6 , 9 caused 6 , 16 , 7 which 8 are 8 are 9 caused 9 caused 10 by 10 by 12 and 11 aggregation 12 and 12 and 13 condensation 13 condensation 14 of 14 of 15 proteins 16 , 17 diminish 17 diminish 18 vision 17 diminish 19 because 19 because 20 they 19 because 21 impede 20 they 21 impede 21 impede 24 and 21 impede 28 on 22 the 23 transmission 23 transmission 24 and 24 and 25 focusing 25 focusing 26 of 26 of 27 light 28 on 30 retina 29 the 30 retina in addition to the slow - developing age - related form , cataracts often develop rapidly as a complication of ocular surgery , such as following vitrectomy or [as] a consequence of vitreous gel degeneration . 0 ###LEFT-WALL### 13 cataracts 0 ###LEFT-WALL### 15 develop 0 ###LEFT-WALL### 36 . 1 in 2 addition 1 in 13 cataracts 2 addition 3 to 3 to 8 age 4 the 8 age 5 slow 6 - 5 slow 8 age 7 developing 8 age 8 age 11 form 9 - 11 form 10 related 11 form 11 form 12 , 13 cataracts 15 develop 14 often 15 develop 15 develop 16 rapidly 15 develop 17 as 17 as 19 complication 17 as 32 of 18 a 19 complication 19 complication 20 of 20 of 28 or 21 ocular 22 surgery 22 surgery 23 , 23 , 27 vitrectomy 23 , 28 or 24 such 27 vitrectomy 25 as 26 following 26 following 27 vitrectomy 28 or 31 consequence 30 a 31 consequence 32 of 35 degeneration 33 vitreous 34 gel 34 gel 35 degeneration posterior capsular opacification , which can develop following cataract removal , is caused by proliferation [and] inappropriate accumulation of lens epithelial cells on the surfaces of intraocular lenses and the posterior lens capsule . 0 ###LEFT-WALL### 3 opacification 0 ###LEFT-WALL### 13 caused 0 ###LEFT-WALL### 34 . 1 posterior 3 opacification 2 capsular 3 opacification 3 opacification 5 which 3 opacification 12 is 4 , 5 which 5 which 6 can 5 which 11 , 6 can 7 develop 7 develop 10 removal 8 following 10 removal 9 cataract 10 removal 12 is 13 caused 13 caused 14 by 13 caused 23 on 14 by 18 accumulation 15 proliferation 18 accumulation 17 inappropriate 18 accumulation 18 accumulation 19 of 19 of 22 cells 20 lens 22 cells 21 epithelial 22 cells 23 on 25 surfaces 24 the 25 surfaces 25 surfaces 26 of 26 of 29 and 27 intraocular 28 lenses 28 lenses 29 and 29 and 33 capsule 30 the 33 capsule 31 posterior 32 lens 32 lens 33 capsule presbyopia is a loss of accommodative amplitude and reduced ability to shift focus from far to near objects . 0 ###LEFT-WALL### 1 presbyopia 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 19 . 1 presbyopia 8 and 2 is 4 loss 2 is 8 and 3 a 4 loss 4 loss 5 of 5 of 7 amplitude 6 accommodative 7 amplitude 8 and 9 reduced 9 reduced 10 ability 9 reduced 15 far 9 reduced 16 to 10 ability 11 to 10 ability 14 from 11 to 12 shift 12 shift 13 focus 12 shift 14 from 16 to 17 near 17 near 18 objects onset of presbyopia is associated with an increase [in] lens hardness and reduced ability of the lens to change shape in response to ciliary muscle contraction . 0 ###LEFT-WALL### 1 onset 0 ###LEFT-WALL### 4 is 0 ###LEFT-WALL### 27 . 1 onset 2 of 1 onset 4 is 2 of 3 presbyopia 4 is 12 and 5 associated 6 with 5 associated 12 and 6 with 11 hardness 7 an 11 hardness 8 increase 10 lens 10 lens 11 hardness 12 and 13 reduced 12 and 14 ability 12 and 18 to 12 and 23 to 14 ability 15 of 15 of 17 lens 16 the 17 lens 18 to 19 change 19 change 20 shape 21 in 22 response 22 response 23 to 23 to 26 contraction 24 ciliary 25 muscle 25 muscle 26 contraction avenues of promising research that seek to delay or prevent these causes of low vision are discussed in light of our current understanding of disease pathogenesis and some challenges that must be met to achieve success . 0 ###LEFT-WALL### 1 avenues 0 ###LEFT-WALL### 35 achieve 0 ###LEFT-WALL### 37 . 1 avenues 2 of 1 avenues 5 that 1 avenues 9 or 1 avenues 13 of 1 avenues 16 are 2 of 3 promising 3 promising 4 research 5 that 9 or 6 seek 7 to 6 seek 8 delay 6 seek 9 or 7 to 8 delay 9 or 10 prevent 10 prevent 12 causes 11 these 12 causes 13 of 15 vision 14 low 15 vision 16 are 17 discussed 17 discussed 18 in 17 discussed 34 to 18 in 27 and 19 light 20 of 19 light 27 and 20 of 23 understanding 21 our 23 understanding 22 current 23 understanding 23 understanding 24 of 24 of 26 pathogenesis 25 disease 26 pathogenesis 27 and 29 challenges 27 and 30 that 27 and 31 must 28 some 29 challenges 30 that 31 must 31 must 32 be 32 be 33 met 34 to 35 achieve 35 achieve 36 success purpose : to examine prevalence of five age - related eye conditions ( age - related cataract , amd , open - angle glaucoma , diabetic retinopathy [ dr ] , and visual impairment ) in the united states . 0 ###LEFT-WALL### 1 purpose 0 ###LEFT-WALL### 2 : 2 : 3 to 2 : 4 examine 2 : 10 related 2 : 15 - 3 to 4 examine 4 examine 5 prevalence 5 prevalence 6 of 6 of 8 age 7 five 8 age 9 - 10 related 10 related 12 conditions 10 related 15 - 11 eye 12 conditions 12 conditions 14 age 13 ( 14 age 14 age 15 - 15 - 17 cataract 15 - 18 , 15 - 40 . 16 related 17 cataract 18 , 32 and 19 amd 27 retinopathy 19 amd 32 and 20 , 27 retinopathy 21 open 24 glaucoma 21 open 25 , 21 open 27 retinopathy 22 - 24 glaucoma 23 angle 24 glaucoma 24 glaucoma 25 , 26 diabetic 27 retinopathy 27 retinopathy 29 dr 27 retinopathy 30 ] 28 [ 29 dr 29 dr 30 ] 31 , 32 and 32 and 34 impairment 32 and 35 ) 32 and 36 in 33 visual 34 impairment 36 in 39 states 37 the 39 states 38 united 39 states methods : review of published scientific articles and unpublished research findings . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 12 . 1 methods 2 : 2 : 3 review 3 review 4 of 4 of 8 and 5 published 7 articles 6 scientific 7 articles 7 articles 8 and 8 and 11 findings 9 unpublished 10 research 10 research 11 findings results : cataract , amd , open - angle glaucoma , dr , and visual impairment prevalences are high in four different studies of these conditions , especially in people over 75 years of age . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 36 . 1 results 2 : 2 : 3 cataract 2 : 28 especially 2 : 31 over 3 cataract 14 and 4 , 14 and 5 amd 10 glaucoma 5 amd 14 and 6 , 10 glaucoma 7 open 8 - 7 open 9 angle 9 angle 10 glaucoma 10 glaucoma 12 dr 10 glaucoma 13 , 11 , 12 dr 12 dr 13 , 13 , 14 and 14 and 16 impairment 14 and 17 prevalences 14 and 18 are 14 and 27 , 15 visual 16 impairment 17 prevalences 18 are 18 are 19 high 18 are 20 in 20 in 23 studies 21 four 23 studies 22 different 23 studies 23 studies 24 of 24 of 26 conditions 25 these 26 conditions 28 especially 29 in 29 in 30 people 31 over 33 years 32 75 33 years 33 years 34 of 34 of 35 age there are disparities among racial/ethnic groups with higher age - specific prevalence of dr , open - angle glaucoma , and visual impairment in hispanics and blacks compared with whites , higher prevalence of age - related cataract in whites compared with blacks , and higher prevalence of late amd in whites compared with hispanics and blacks . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 are 0 ###LEFT-WALL### 58 . 1 there 2 are 2 are 3 disparities 2 are 4 among 2 are 7 with 2 are 39 in 4 among 6 groups 5 racial/ethnic 6 groups 7 with 9 age 7 with 21 and 8 higher 9 age 9 age 12 prevalence 10 - 12 prevalence 11 specific 12 prevalence 12 prevalence 13 of 12 prevalence 15 , 13 of 14 dr 16 open 17 - 16 open 18 angle 18 angle 19 glaucoma 19 glaucoma 21 and 20 , 21 and 21 and 38 cataract 22 visual 38 cataract 23 impairment 24 in 23 impairment 26 and 24 in 25 hispanics 26 and 27 blacks 26 and 38 cataract 27 blacks 28 compared 28 compared 29 with 28 compared 36 - 28 compared 37 related 29 with 30 whites 30 whites 33 prevalence 31 , 33 prevalence 32 higher 33 prevalence 33 prevalence 34 of 33 prevalence 36 - 34 of 35 age 39 in 40 whites 40 whites 41 compared 40 whites 50 amd 40 whites 53 compared 41 compared 42 with 41 compared 49 late 42 with 47 prevalence 43 blacks 45 and 44 , 45 and 45 and 46 higher 45 and 47 prevalence 48 of 49 late 50 amd 51 in 50 amd 53 compared 51 in 52 whites 53 compared 54 with 54 with 56 and 55 hispanics 56 and 56 and 57 blacks the estimates are based [on] old data and do not reflect recent changes in the distribution of age and race/ethnicity in the united states population . 0 ###LEFT-WALL### 2 estimates 0 ###LEFT-WALL### 3 are 0 ###LEFT-WALL### 26 . 1 the 2 estimates 2 estimates 3 are 3 are 8 and 4 based 7 data 4 based 8 and 6 old 7 data 8 and 9 do 9 do 10 not 9 do 11 reflect 11 reflect 13 changes 11 reflect 14 in 11 reflect 21 in 12 recent 13 changes 14 in 19 and 15 the 16 distribution 16 distribution 17 of 16 distribution 19 and 17 of 18 age 19 and 20 race/ethnicity 21 in 25 population 22 the 25 population 23 united 24 states 24 states 25 population there are no epidemiologic estimates of prevalence for many visually - impairing conditions . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 are 1 there 2 are 2 are 5 estimates 2 are 10 visually 2 are 12 impairing 3 no 5 estimates 4 epidemiologic 5 estimates 5 estimates 6 of 6 of 7 prevalence 7 prevalence 8 for 8 for 9 many 11 - 12 impairing 12 impairing 13 conditions 12 impairing 14 . conclusions : ongoing prevalence surveys designed to provide reliable estimates of visual impairment , amd , age - related cataract , open - angle glaucoma , and dr are needed . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 16 , 1 conclusions 2 : 2 : 3 ongoing 2 : 7 to 3 ongoing 5 surveys 3 ongoing 6 designed 4 prevalence 5 surveys 5 surveys 6 designed 7 to 8 provide 8 provide 10 estimates 9 reliable 10 estimates 10 estimates 11 of 10 estimates 15 amd 11 of 13 impairment 12 visual 13 impairment 14 , 15 amd 15 amd 16 , 16 , 17 age 16 , 18 - 18 - 20 cataract 18 - 21 , 18 - 31 . 19 related 20 cataract 21 , 27 and 21 , 29 are 22 open 23 - 22 open 24 angle 24 angle 25 glaucoma 25 glaucoma 27 and 26 , 27 and 27 and 28 dr 27 and 29 are 29 are 30 needed it is important to collect objective data on these and other conditions that affect vision and quality of life in order to plan for health care needs and identify areas for further research . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 34 . 1 it 2 is 2 is 3 important 3 important 4 to 3 important 5 collect 4 to 5 collect 5 collect 16 and 5 collect 20 in 6 objective 7 data 7 data 8 on 7 data 16 and 8 on 10 and 9 these 10 and 10 and 12 conditions 10 and 13 that 10 and 14 affect 11 other 12 conditions 13 that 14 affect 14 affect 15 vision 16 and 17 quality 16 and 18 of 18 of 19 life 20 in 21 order 21 order 22 to 21 order 28 and 22 to 28 and 23 plan 26 care 23 plan 27 needs 23 plan 28 and 24 for 25 health 24 for 26 care 26 care 27 needs 28 and 29 identify 28 and 30 areas 30 areas 31 for 31 for 33 research 32 further 33 research aging of the ocular surface and corneal tissues , major components of the visual system , causes major eye disease and results in substantial cost in medical and social terms . 0 ###LEFT-WALL### 1 aging 0 ###LEFT-WALL### 21 and 0 ###LEFT-WALL### 31 . 1 aging 2 of 1 aging 11 components 1 aging 21 and 2 of 6 and 3 the 5 surface 4 ocular 5 surface 5 surface 6 and 6 and 8 tissues 7 corneal 8 tissues 9 , 11 components 10 major 11 components 11 components 12 of 11 components 16 , 12 of 15 system 13 the 15 system 14 visual 15 system 17 causes 20 disease 17 causes 21 and 18 major 20 disease 19 eye 20 disease 21 and 22 results 22 results 23 in 22 results 26 in 23 in 25 cost 24 substantial 25 cost 26 in 30 terms 27 medical 28 and 28 and 29 social 28 and 30 terms these diseases include the highly prevalent dry eye disease that affects the ocular surface and its glands , leading to tear film alterations , discomfort , and decreased vision . 0 ###LEFT-WALL### 2 diseases 0 ###LEFT-WALL### 30 . 1 these 2 diseases 2 diseases 27 and 3 include 9 disease 3 include 19 leading 3 include 27 and 4 the 9 disease 5 highly 6 prevalent 6 prevalent 8 eye 7 dry 8 eye 8 eye 9 disease 9 disease 10 that 9 disease 11 affects 10 that 11 affects 11 affects 15 and 12 the 14 surface 13 ocular 14 surface 14 surface 15 and 15 and 17 glands 16 its 17 glands 18 , 19 leading 19 leading 20 to 19 leading 26 , 20 to 23 alterations 21 tear 22 film 22 film 23 alterations 23 alterations 25 discomfort 24 , 25 discomfort 25 discomfort 26 , 27 and 28 decreased 28 decreased 29 vision studies show that 14.4 % of the population in the united states older than 50 years have dry eye disease and demonstrate that it is particularly prevalent among women . 0 ###LEFT-WALL### 1 studies 0 ###LEFT-WALL### 21 and 0 ###LEFT-WALL### 30 . 1 studies 21 and 2 show 3 that 2 show 21 and 3 that 5 % 3 that 17 have 4 14.4 5 % 5 % 6 of 5 % 17 have 6 of 8 population 7 the 8 population 8 population 9 in 9 in 12 states 10 the 12 states 11 united 12 states 12 states 13 older 13 older 14 than 14 than 16 years 15 50 16 years 17 have 20 disease 18 dry 19 eye 19 eye 20 disease 21 and 22 demonstrate 21 and 28 among 22 demonstrate 23 that 23 that 24 it 23 that 25 is 24 it 25 is 25 is 27 prevalent 26 particularly 27 prevalent 28 among 29 women annual medical costs per patient [with] dry eye in the united states are estimated at $ 783 per year , with an overall medical cost adjusted to prevalence of $ 3.84 billion per year . 0 ###LEFT-WALL### 3 costs 0 ###LEFT-WALL### 14 estimated 0 ###LEFT-WALL### 20 , 0 ###LEFT-WALL### 35 . 1 annual 3 costs 2 medical 3 costs 3 costs 4 per 3 costs 9 in 3 costs 13 are 4 per 8 eye 5 patient 8 eye 7 dry 8 eye 9 in 12 states 10 the 12 states 11 united 12 states 13 are 14 estimated 14 estimated 15 at 15 at 16 $ 16 $ 17 783 16 $ 18 per 18 per 19 year 20 , 25 cost 20 , 26 adjusted 21 with 23 overall 21 with 25 cost 22 an 23 overall 24 medical 25 cost 25 cost 26 adjusted 26 adjusted 27 to 27 to 28 prevalence 28 prevalence 29 of 28 prevalence 33 per 29 of 30 $ 30 $ 32 billion 31 3.84 32 billion 33 per 34 year societal costs , which include loss of productivity , are estimated per patient at $ 11,302 per year [,] with overall costs adjusted to prevalence of $ 55.4 billion per year . 0 ###LEFT-WALL### 1 societal 0 ###LEFT-WALL### 23 adjusted 0 ###LEFT-WALL### 32 . 1 societal 2 costs 1 societal 10 are 1 societal 11 estimated 1 societal 12 per 1 societal 14 at 1 societal 23 adjusted 2 costs 4 which 2 costs 10 are 3 , 4 which 4 which 5 include 4 which 9 , 5 include 6 loss 6 loss 7 of 7 of 8 productivity 12 per 13 patient 14 at 15 $ 15 $ 16 11,302 15 $ 17 per 15 $ 20 with 17 per 18 year 20 with 22 costs 21 overall 22 costs 23 adjusted 24 to 24 to 25 prevalence 25 prevalence 26 of 25 prevalence 30 per 26 of 27 $ 27 $ 29 billion 28 55.4 29 billion 30 per 31 year because there are few effective treatments for the disease , more research on its etiology and mechanisms is warranted and needed . 0 ###LEFT-WALL### 12 research 0 ###LEFT-WALL### 18 is 0 ###LEFT-WALL### 22 . 1 because 2 there 1 because 3 are 1 because 10 , 1 because 12 research 2 there 3 are 3 are 6 treatments 4 few 6 treatments 5 effective 6 treatments 6 treatments 7 for 7 for 9 disease 8 the 9 disease 11 more 12 research 12 research 13 on 12 research 18 is 13 on 16 and 14 its 15 etiology 15 etiology 16 and 16 and 17 mechanisms 18 is 20 and 19 warranted 20 and 20 and 21 needed increased public education about risk factors for the disease is also required . 0 ###LEFT-WALL### 3 education 0 ###LEFT-WALL### 12 required 0 ###LEFT-WALL### 13 . 1 increased 3 education 2 public 3 education 3 education 4 about 3 education 10 is 4 about 6 factors 5 risk 6 factors 6 factors 7 for 7 for 9 disease 8 the 9 disease 10 is 11 also 10 is 12 required another major age - related eye disease of the cornea that leads to vision impairment and potentially blindness if left untreated is fuchs ' endothelial corneal dystrophy . 0 ###LEFT-WALL### 3 age 0 ###LEFT-WALL### 22 is 0 ###LEFT-WALL### 28 . 1 another 3 age 2 major 3 age 3 age 13 to 3 age 14 vision 3 age 22 is 4 - 5 related 5 related 7 disease 5 related 13 to 6 eye 7 disease 7 disease 8 of 8 of 10 cornea 9 the 10 cornea 10 cornea 11 that 10 cornea 12 leads 11 that 12 leads 13 to 14 vision 14 vision 16 and 14 vision 19 if 15 impairment 16 and 16 and 17 potentially 16 and 18 blindness 19 if 20 left 20 left 21 untreated 22 is 27 dystrophy 23 fuchs 24 ' 24 ' 27 dystrophy 25 endothelial 27 dystrophy 26 corneal 27 dystrophy this disease leads to loss of the endothelial cells on the internal side of the cornea that are responsible for keeping the cornea in the proper hydration state to ensure its transparency to light . 0 ###LEFT-WALL### 2 disease 0 ###LEFT-WALL### 30 ensure 0 ###LEFT-WALL### 35 . 1 this 2 disease 2 disease 3 leads 3 leads 4 to 3 leads 29 to 4 to 5 loss 5 loss 6 of 6 of 9 cells 7 the 9 cells 8 endothelial 9 cells 9 cells 10 on 9 cells 14 of 9 cells 17 that 9 cells 18 are 10 on 13 side 11 the 13 side 12 internal 13 side 14 of 16 cornea 15 the 16 cornea 17 that 18 are 18 are 19 responsible 19 responsible 20 for 19 responsible 24 in 20 for 21 keeping 21 keeping 23 cornea 22 the 23 cornea 24 in 28 state 25 the 28 state 26 proper 28 state 27 hydration 28 state 29 to 30 ensure 30 ensure 32 transparency 31 its 32 transparency 32 transparency 33 to 32 transparency 34 light 33 to 34 light the mechanism of cell loss is unknown , and the only treatment available to date is surgical transplantation of the cornea or inner part of the cornea . 0 ###LEFT-WALL### 2 mechanism 0 ###LEFT-WALL### 6 is 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 28 . 1 the 2 mechanism 2 mechanism 3 of 2 mechanism 6 is 3 of 5 loss 4 cell 5 loss 6 is 7 unknown 8 , 9 and 9 and 12 treatment 9 and 16 is 10 the 11 only 10 the 12 treatment 12 treatment 13 available 12 treatment 16 is 13 available 15 date 14 to 15 date 16 is 18 transplantation 17 surgical 18 transplantation 18 transplantation 19 of 19 of 22 or 20 the 21 cornea 21 cornea 22 or 22 or 24 part 22 or 25 of 23 inner 24 part 25 of 27 cornea 26 the 27 cornea these medically costly procedures require donor corneas , eye banking , and medical follow - up , with [accrued] costs . 0 ###LEFT-WALL### 4 procedures 0 ###LEFT-WALL### 5 require 0 ###LEFT-WALL### 21 . 1 these 4 procedures 2 medically 3 costly 3 costly 4 procedures 4 procedures 5 require 5 require 12 and 5 require 14 follow 6 donor 7 corneas 7 corneas 8 , 8 , 10 banking 8 , 12 and 9 eye 10 banking 11 , 12 and 12 and 13 medical 14 follow 16 up 14 follow 18 with 15 - 16 up 16 up 17 , 18 with 20 costs fuchs ' endothelial corneal dystrophy is a major cause of corneal transplantation in the united states ; therefore , research support is needed to determine the mechanism of this age - related disease , to develop medical , nonsurgical methods for treatment . 0 ###LEFT-WALL### 5 dystrophy 0 ###LEFT-WALL### 6 is 0 ###LEFT-WALL### 17 ; 0 ###LEFT-WALL### 43 . 1 fuchs 2 ' 2 ' 5 dystrophy 3 endothelial 5 dystrophy 4 corneal 5 dystrophy 5 dystrophy 6 is 6 is 9 cause 7 a 8 major 7 a 9 cause 8 major 9 cause 9 cause 10 of 9 cause 13 in 10 of 12 transplantation 11 corneal 12 transplantation 13 in 16 states 14 the 16 states 15 united 16 states 17 ; 21 support 17 ; 23 needed 18 therefore 19 , 18 therefore 21 support 20 research 21 support 21 support 22 is 22 is 23 needed 23 needed 24 to 24 to 25 determine 25 determine 27 mechanism 25 determine 35 to 26 the 27 mechanism 27 mechanism 28 of 28 of 30 age 29 this 30 age 30 age 33 disease 31 - 33 disease 32 related 33 disease 33 disease 34 , 35 to 36 develop 36 develop 40 methods 36 develop 41 for 37 medical 38 , 37 medical 40 methods 39 nonsurgical 40 methods 41 for 42 treatment purpose : we reviewed the data from the clinical trials of nutritional supplements for the treatment of age - related cataract [and] age - related macular degeneration ( amd ) to determine future directions of research and treatment . 0 ###LEFT-WALL### 1 purpose 0 ###LEFT-WALL### 2 : 2 : 3 we 2 : 4 reviewed 2 : 20 related 3 we 4 reviewed 4 reviewed 6 data 5 the 6 data 6 data 7 from 6 data 11 of 6 data 14 for 6 data 17 of 7 from 10 trials 8 the 10 trials 9 clinical 10 trials 11 of 13 supplements 12 nutritional 13 supplements 14 for 16 treatment 15 the 16 treatment 17 of 18 age 19 - 20 related 20 related 23 age 20 related 31 to 20 related 39 . 21 cataract 23 age 24 - 25 related 25 related 27 degeneration 25 related 30 ) 25 related 31 to 26 macular 27 degeneration 27 degeneration 29 amd 28 ( 29 amd 29 amd 30 ) 31 to 32 determine 32 determine 37 and 33 future 34 directions 34 directions 35 of 34 directions 37 and 35 of 36 research 37 and 38 treatment methods : data from the controlled clinical trials are presented and reviewed for potential opportunities for further research into the treatment of cataracts and amd . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 26 . 2 : 3 data 2 : 11 and 3 data 4 from 3 data 9 are 4 from 8 trials 5 the 8 trials 6 controlled 8 trials 7 clinical 8 trials 9 are 11 and 10 presented 11 and 11 and 12 reviewed 11 and 13 for 11 and 15 opportunities 13 for 14 potential 15 opportunities 16 for 15 opportunities 19 into 15 opportunities 22 of 16 for 18 research 17 further 18 research 19 into 21 treatment 20 the 21 treatment 22 of 24 and 23 cataracts 24 and 24 and 25 amd results : two trials using daily multivitamins/minerals demonstrated a reduction in the progression [of] nuclear cataract , but increased the risk [of] posterior subcapsular cataract . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 26 . 2 : 4 trials 2 : 18 but 3 two 4 trials 4 trials 5 using 4 trials 18 but 5 using 7 multivitamins/minerals 6 daily 7 multivitamins/minerals 8 demonstrated 10 reduction 8 demonstrated 11 in 8 demonstrated 18 but 9 a 10 reduction 11 in 16 cataract 12 the 16 cataract 13 progression 16 cataract 15 nuclear 16 cataract 17 , 18 but 18 but 19 increased 19 increased 25 cataract 20 the 25 cataract 21 risk 25 cataract 23 posterior 25 cataract 24 subcapsular 25 cataract for amd , the age - related eye disease study ( areds ) formulation ( vitamins c , [e] , beta - carotene , zinc , and copper ) reduced the risk of progression to advanced amd by 25 % at 5 years . 0 ###LEFT-WALL### 14 formulation 0 ###LEFT-WALL### 30 reduced 0 ###LEFT-WALL### 44 . 1 for 2 amd 1 for 14 formulation 2 amd 5 age 3 , 5 age 4 the 5 age 5 age 6 - 6 - 7 related 7 related 9 disease 7 related 14 formulation 8 eye 9 disease 10 study 12 areds 11 ( 12 areds 12 areds 13 ) 12 areds 14 formulation 14 formulation 16 vitamins 14 formulation 21 beta 14 formulation 27 and 14 formulation 30 reduced 15 ( 16 vitamins 16 vitamins 17 c 16 vitamins 18 , 20 , 21 beta 21 beta 22 - 22 - 27 and 23 carotene 24 , 24 , 25 zinc 24 , 27 and 26 , 27 and 27 and 28 copper 27 and 29 ) 30 reduced 32 risk 30 reduced 38 by 31 the 32 risk 32 risk 33 of 33 of 34 progression 34 progression 35 to 35 to 37 amd 36 advanced 37 amd 38 by 40 % 39 25 40 % 40 % 41 at 41 at 43 years 42 5 43 years because beta [-] carotene is associated with increased lung cancer in former smokers , lutein/zeaxanthin could replace beta - [carotene] and provide an incremental increase in the beneficial effects beyond the effects of the areds formulation . 0 ###LEFT-WALL### 15 lutein/zeaxanthin 0 ###LEFT-WALL### 21 and 0 ###LEFT-WALL### 37 . 1 because 4 carotene 1 because 6 associated 1 because 14 , 1 because 15 lutein/zeaxanthin 2 beta 4 carotene 4 carotene 5 is 5 is 6 associated 6 associated 7 with 6 associated 11 in 7 with 10 cancer 8 increased 10 cancer 9 lung 10 cancer 11 in 13 smokers 12 former 13 smokers 15 lutein/zeaxanthin 16 could 16 could 21 and 17 replace 18 beta 17 replace 21 and 19 - 21 and 21 and 22 provide 22 provide 25 increase 22 provide 30 beyond 23 an 24 incremental 23 an 25 increase 24 incremental 25 increase 25 increase 26 in 26 in 29 effects 27 the 29 effects 28 beneficial 29 effects 30 beyond 32 effects 31 the 32 effects 32 effects 33 of 33 of 36 formulation 34 the 36 formulation 35 areds 36 formulation in addition , a randomized clinical trial of b [vitamins] demonstrated a beneficial effect for amd with the vitamin b complex . 0 ###LEFT-WALL### 7 trial 0 ###LEFT-WALL### 11 demonstrated 0 ###LEFT-WALL### 22 . 1 in 2 addition 1 in 3 , 1 in 7 trial 4 a 7 trial 5 randomized 7 trial 6 clinical 7 trial 7 trial 8 of 7 trial 11 demonstrated 8 of 9 b 11 demonstrated 14 effect 11 demonstrated 17 with 12 a 13 beneficial 12 a 14 effect 13 beneficial 14 effect 14 effect 15 for 15 for 16 amd 17 with 21 complex 18 the 21 complex 19 vitamin 20 b 19 vitamin 21 complex conclusions : future [evaluation] may include additional assessments of nutrients for the treatment of progression of cataract [and] amd . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 3 future 2 : 6 include 2 : 20 . 3 future 5 may 5 may 6 include 6 include 8 assessments 7 additional 8 assessments 8 assessments 9 of 8 assessments 11 for 9 of 10 nutrients 11 for 13 treatment 12 the 13 treatment 13 treatment 14 of 14 of 15 progression 15 progression 16 of 16 of 19 amd 17 cataract 19 amd a modest reduction would have significant impact as the numbers of persons affected with these two leading causes of blindness are projected to double in the next decade . 0 ###LEFT-WALL### 3 reduction 0 ###LEFT-WALL### 5 have 0 ###LEFT-WALL### 29 . 1 a 2 modest 1 a 3 reduction 2 modest 3 reduction 3 reduction 4 would 4 would 5 have 5 have 7 impact 5 have 8 as 5 have 13 affected 6 significant 7 impact 8 as 10 numbers 9 the 10 numbers 10 numbers 11 of 11 of 12 persons 13 affected 14 with 13 affected 24 double 14 with 16 two 15 these 16 two 16 two 17 leading 16 two 18 causes 16 two 23 to 18 causes 19 of 18 causes 21 are 19 of 20 blindness 21 are 22 projected 22 projected 23 to 24 double 25 in 25 in 28 decade 26 the 27 next 26 the 28 decade an important step would be to develop surrogate outcomes to increase efficiency in clinical trials . 0 ###LEFT-WALL### 3 step 0 ###LEFT-WALL### 11 increase 0 ###LEFT-WALL### 16 . 1 an 2 important 1 an 3 step 2 important 3 step 3 step 4 would 4 would 5 be 5 be 6 to 5 be 7 develop 6 to 7 develop 7 develop 9 outcomes 7 develop 10 to 8 surrogate 9 outcomes 10 to 11 increase 11 increase 12 efficiency 11 increase 13 in 13 in 15 trials 14 clinical 15 trials more detailed phenotyping , especially of amd , is required as it appears to be not one disease , but a group of diseases . 0 ###LEFT-WALL### 3 phenotyping 0 ###LEFT-WALL### 15 be 0 ###LEFT-WALL### 25 . 1 more 3 phenotyping 2 detailed 3 phenotyping 3 phenotyping 6 of 3 phenotyping 9 is 4 , 5 especially 4 , 6 of 6 of 7 amd 6 of 8 , 9 is 10 required 10 required 11 as 11 as 12 it 11 as 13 appears 12 it 13 appears 13 appears 14 to 14 to 15 be 15 be 20 but 16 not 20 but 17 one 18 disease 18 disease 20 but 19 , 20 but 20 but 22 group 21 a 22 group 22 group 23 of 23 of 24 diseases [genotype] - phenotype analyses may help to target pathways that are important in amd . 0 ###LEFT-WALL### 2 - 0 ###LEFT-WALL### 6 help 0 ###LEFT-WALL### 15 . 2 - 4 analyses 3 phenotype 4 analyses 4 analyses 5 may 5 may 6 help 6 help 7 to 6 help 8 target 7 to 8 target 8 target 9 pathways 9 pathways 10 that 9 pathways 11 are 10 that 11 are 11 are 12 important 12 important 13 in 13 in 14 amd none age - related macular degeneration ( amd ) , cataract , glaucoma and diabetic retinopathy are common causes of visual loss . 0 ###LEFT-WALL### 1 none 0 ###LEFT-WALL### 17 are 0 ###LEFT-WALL### 23 . 1 none 14 and 1 none 16 retinopathy 1 none 17 are 2 age 6 degeneration 2 age 10 , 3 - 6 degeneration 4 related 6 degeneration 5 macular 6 degeneration 6 degeneration 8 amd 6 degeneration 9 ) 7 ( 8 amd 8 amd 9 ) 10 , 11 cataract 10 , 12 , 12 , 13 glaucoma 12 , 14 and 14 and 15 diabetic 14 and 16 retinopathy 17 are 19 causes 18 common 19 causes 19 causes 20 of 20 of 22 loss 21 visual 22 loss both environmental and genetic factors contribute to the development of these diseases . 0 ###LEFT-WALL### 5 factors 0 ###LEFT-WALL### 6 contribute 0 ###LEFT-WALL### 13 . 1 both 5 factors 2 environmental 3 and 3 and 4 genetic 3 and 5 factors 5 factors 6 contribute 6 contribute 7 to 7 to 9 development 8 the 9 development 9 development 10 of 10 of 12 diseases 11 these 12 diseases the modifiable factors related to some of these age - related [and] visually threatening diseases are smoking , obesity , and dietary factors , and a cardiovascular risk profile . 0 ###LEFT-WALL### 3 factors 0 ###LEFT-WALL### 9 age 0 ###LEFT-WALL### 11 related 1 the 3 factors 2 modifiable 3 factors 3 factors 4 related 3 factors 9 age 4 related 5 to 5 to 6 some 6 some 7 of 7 of 8 these 10 - 11 related 11 related 14 threatening 11 related 30 . 13 visually 14 threatening 14 threatening 15 diseases 14 threatening 16 are 15 diseases 16 are 16 are 21 and 17 smoking 18 , 18 , 19 obesity 18 , 21 and 20 , 21 and 21 and 29 profile 22 dietary 23 factors 23 factors 25 and 24 , 25 and 25 and 28 risk 25 and 29 profile 26 a 28 risk 27 cardiovascular 28 risk many common and a few rare genetic factors are associated with amd . 0 ###LEFT-WALL### 1 many 0 ###LEFT-WALL### 10 associated 0 ###LEFT-WALL### 13 . 1 many 3 and 1 many 9 are 1 many 10 associated 2 common 3 and 3 and 8 factors 3 and 9 are 4 a 5 few 5 few 8 factors 6 rare 8 factors 7 genetic 8 factors 10 associated 11 with 11 with 12 amd the role [of] genetic variants for the other diseases are less clear . 0 ###LEFT-WALL### 5 variants 0 ###LEFT-WALL### 10 are 0 ###LEFT-WALL### 13 . 1 the 5 variants 2 role 5 variants 4 genetic 5 variants 5 variants 6 for 5 variants 10 are 6 for 9 diseases 7 the 8 other 8 other 9 diseases 10 are 12 clear 11 less 12 clear interactions between environmental , therapeutic , and genetic factors are being explored . 0 ###LEFT-WALL### 1 interactions 0 ###LEFT-WALL### 10 are 0 ###LEFT-WALL### 13 . 1 interactions 2 between 1 interactions 10 are 2 between 9 factors 3 environmental 4 , 4 , 5 therapeutic 4 , 7 and 6 , 7 and 7 and 8 genetic 7 and 9 factors 10 are 11 being 11 being 12 explored knowledge of genetic risk and environmental factors , especially for amd , has grown markedly over the past 2.5 decades and has led to some sight - saving approaches in preventive management . 0 ###LEFT-WALL### 1 knowledge 0 ###LEFT-WALL### 21 and 1 knowledge 2 of 1 knowledge 21 and 2 of 5 and 3 genetic 4 risk 4 risk 5 and 5 and 7 factors 5 and 10 for 6 environmental 7 factors 8 , 9 especially 8 , 10 for 10 for 11 amd 10 for 12 , 13 has 14 grown 13 has 21 and 14 grown 15 markedly 14 grown 16 over 16 over 20 decades 17 the 18 past 17 the 19 2.5 19 2.5 20 decades 21 and 22 has 21 and 28 saving 22 has 23 led 23 led 24 to 24 to 26 sight 25 some 26 sight 27 - 28 saving 28 saving 29 approaches 28 saving 30 in 28 saving 33 . 30 in 32 management 31 preventive 32 management purpose : we described anatomic age - related changes in the human eye to determine potential areas of investigation that may lead to identifying eyes at risk for age - related disease . 0 ###LEFT-WALL### 1 purpose 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 33 . 2 : 3 we 2 : 4 described 2 : 8 related 2 : 30 - 3 we 4 described 4 described 6 age 5 anatomic 6 age 7 - 8 related 8 related 9 changes 8 related 14 to 8 related 23 to 9 changes 10 in 10 in 13 eye 11 the 13 eye 12 human 13 eye 14 to 15 determine 15 determine 17 areas 16 potential 17 areas 17 areas 18 of 18 of 19 investigation 19 investigation 20 that 19 investigation 21 may 20 that 21 may 21 may 22 lead 23 to 24 identifying 24 identifying 25 eyes 25 eyes 26 at 26 at 27 risk 27 risk 28 for 28 for 29 age 30 - 32 disease 31 related 32 disease methods : a descriptive review of anatomic changes in the eye related to aging was performed in the context of current areas of investigation . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 5 review 2 : 16 performed 2 : 25 . 3 a 4 descriptive 3 a 5 review 4 descriptive 5 review 5 review 6 of 5 review 15 was 6 of 8 changes 7 anatomic 8 changes 8 changes 9 in 8 changes 12 related 9 in 11 eye 10 the 11 eye 12 related 13 to 13 to 14 aging 15 was 16 performed 16 performed 17 in 17 in 19 context 18 the 19 context 19 context 20 of 20 of 22 areas 21 current 22 areas 22 areas 23 of 23 of 24 investigation the review was performed specifically for differing anatomic ocular structures , including cornea , trabecular meshwork , lens , uveal tract , bruch 's membrane , retina , rpe , vitreous , sclera , and optic nerve . 0 ###LEFT-WALL### 2 review 0 ###LEFT-WALL### 4 performed 0 ###LEFT-WALL### 11 , 0 ###LEFT-WALL### 38 . 1 the 2 review 2 review 3 was 3 was 4 performed 4 performed 5 specifically 4 performed 6 for 6 for 10 structures 7 differing 10 structures 8 anatomic 10 structures 9 ocular 10 structures 11 , 13 cornea 11 , 14 , 12 including 13 cornea 14 , 35 and 15 trabecular 16 meshwork 16 meshwork 17 , 17 , 18 lens 17 , 19 , 19 , 21 tract 19 , 22 , 20 uveal 21 tract 22 , 25 membrane 22 , 26 , 23 bruch 24 's 24 's 25 membrane 26 , 27 retina 26 , 28 , 28 , 29 rpe 28 , 30 , 30 , 33 sclera 30 , 35 and 31 vitreous 32 , 31 vitreous 33 sclera 34 , 35 and 35 and 37 nerve 36 optic 37 nerve results : age - related changes occur in all ocular tissues . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 4 - 1 results 2 : 2 : 3 age 4 - 6 changes 4 - 7 occur 4 - 12 . 5 related 6 changes 6 changes 7 occur 7 occur 8 in 8 in 11 tissues 9 all 11 tissues 10 ocular 11 tissues the cornea flattens and there is [an] attrition of endothelial cells . 0 ###LEFT-WALL### 2 cornea 0 ###LEFT-WALL### 3 flattens 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 12 . 1 the 2 cornea 2 cornea 3 flattens 4 and 5 there 4 and 6 is 5 there 6 is 6 is 8 attrition 8 attrition 9 of 9 of 11 cells 10 endothelial 11 cells the shape of the trabecular meshwork changes and there is a loss of trabecular endothelium . 0 ###LEFT-WALL### 2 shape 0 ###LEFT-WALL### 7 changes 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 16 . 1 the 2 shape 2 shape 3 of 2 shape 7 changes 3 of 6 meshwork 4 the 6 meshwork 5 trabecular 6 meshwork 8 and 9 there 8 and 10 is 9 there 10 is 10 is 12 loss 11 a 12 loss 12 loss 13 of 13 of 15 endothelium 14 trabecular 15 endothelium the lens grows and becomes cataractous . 0 ###LEFT-WALL### 2 lens 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 7 . 1 the 2 lens 2 lens 4 and 3 grows 4 and 4 and 5 becomes 5 becomes 6 cataractous the ciliary body becomes collagenized , there are choroidal vascular changes , and bruch 's membrane thickens . 0 ###LEFT-WALL### 3 body 0 ###LEFT-WALL### 4 becomes 0 ###LEFT-WALL### 6 , 0 ###LEFT-WALL### 18 . 1 the 3 body 2 ciliary 3 body 3 body 4 becomes 4 becomes 5 collagenized 6 , 7 there 6 , 8 are 6 , 13 and 7 there 8 are 8 are 11 changes 9 choroidal 11 changes 10 vascular 11 changes 12 , 13 and 13 and 16 membrane 13 and 17 thickens 14 bruch 15 's 15 's 16 membrane 16 membrane 17 thickens retinal vessels become hyalinized and there is a loss of rods before cones in the macula . 0 ###LEFT-WALL### 2 vessels 0 ###LEFT-WALL### 3 become 0 ###LEFT-WALL### 5 and 0 ###LEFT-WALL### 17 . 1 retinal 2 vessels 2 vessels 3 become 3 become 4 hyalinized 5 and 6 there 5 and 7 is 6 there 7 is 7 is 9 loss 8 a 9 loss 9 loss 10 of 10 of 11 rods 11 rods 12 before 12 before 13 cones 13 cones 14 in 14 in 16 macula 15 the 16 macula rpe morphometric changes occur with aging . 0 ###LEFT-WALL### 3 changes 0 ###LEFT-WALL### 4 occur 0 ###LEFT-WALL### 7 . 1 rpe 3 changes 2 morphometric 3 changes 3 changes 4 occur 4 occur 5 with 5 with 6 aging the vitreous [becomes] liquefied and there is a loss of vitreous compartmentalization . 0 ###LEFT-WALL### 2 vitreous 0 ###LEFT-WALL### 4 liquefied 0 ###LEFT-WALL### 5 and 0 ###LEFT-WALL### 13 . 1 the 2 vitreous 2 vitreous 4 liquefied 5 and 6 there 5 and 7 is 6 there 7 is 7 is 9 loss 8 a 9 loss 9 loss 10 of 10 of 12 compartmentalization 11 vitreous 12 compartmentalization the sclera becomes rigid and may become calcified . 0 ###LEFT-WALL### 2 sclera 0 ###LEFT-WALL### 5 and 0 ###LEFT-WALL### 9 . 1 the 2 sclera 2 sclera 5 and 3 becomes 4 rigid 3 becomes 5 and 5 and 6 may 6 may 7 become 7 become 8 calcified the optic nerve exhibits structural changes with age . 0 ###LEFT-WALL### 3 nerve 0 ###LEFT-WALL### 4 exhibits 0 ###LEFT-WALL### 9 . 1 the 3 nerve 2 optic 3 nerve 3 nerve 4 exhibits 4 exhibits 6 changes 4 exhibits 7 with 5 structural 6 changes 7 with 8 age conclusions : there [are] numerous anatomic age - related changes in the human eye . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 9 related 1 conclusions 2 : 2 : 7 age 3 there 7 age 5 numerous 7 age 6 anatomic 7 age 8 - 9 related 9 related 10 changes 9 related 11 in 9 related 15 . 11 in 14 eye 12 the 14 eye 13 human 14 eye current areas of investigation related to these changes include adaptive optics scanning laser ophthalmoscopy imaging of the rpe mosaic in the context of aging , and drug delivery devices that overcome age - related alterations to retinal and macular perfusion . 0 ###LEFT-WALL### 2 areas 0 ###LEFT-WALL### 5 related 0 ###LEFT-WALL### 34 related 0 ###LEFT-WALL### 41 . 1 current 2 areas 2 areas 3 of 2 areas 5 related 3 of 4 investigation 5 related 6 to 5 related 15 imaging 6 to 8 changes 7 these 8 changes 9 include 11 optics 10 adaptive 11 optics 11 optics 15 imaging 12 scanning 15 imaging 13 laser 15 imaging 14 ophthalmoscopy 15 imaging 15 imaging 16 of 16 of 19 mosaic 17 the 19 mosaic 18 rpe 19 mosaic 19 mosaic 20 in 19 mosaic 23 of 20 in 22 context 21 the 22 context 23 of 29 devices 24 aging 26 and 25 , 26 and 26 and 27 drug 26 and 28 delivery 28 delivery 29 devices 29 devices 30 that 29 devices 31 overcome 30 that 31 overcome 31 overcome 32 age 33 - 34 related 34 related 35 alterations 34 related 36 to 36 to 40 perfusion 37 retinal 38 and 38 and 39 macular 38 and 40 perfusion purpose : to examine projections of age - related eye diseases in the united states for health care planning . 0 ###LEFT-WALL### 1 purpose 0 ###LEFT-WALL### 2 : 2 : 3 to 2 : 4 examine 2 : 9 related 3 to 4 examine 4 examine 5 projections 5 projections 6 of 6 of 7 age 8 - 9 related 9 related 11 diseases 9 related 12 in 9 related 16 for 9 related 20 . 10 eye 11 diseases 12 in 15 states 13 the 15 states 14 united 15 states 16 for 18 care 17 health 18 care 18 care 19 planning methods : review of published scientific articles , census data , and unpublished research findings . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 16 . 1 methods 2 : 2 : 3 review 3 review 4 of 4 of 12 and 5 published 7 articles 6 scientific 7 articles 7 articles 8 , 8 , 10 data 8 , 12 and 9 census 10 data 11 , 12 and 12 and 15 findings 13 unpublished 14 research 14 research 15 findings results : the numbers of cases of all age - related eye diseases are expected to rise in the coming years . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 22 . 2 : 6 cases 2 : 15 expected 3 the 4 numbers 4 numbers 5 of 4 numbers 6 cases 5 of 6 cases 6 cases 7 of 6 cases 14 are 7 of 9 age 8 all 9 age 10 - 11 related 11 related 13 diseases 11 related 14 are 12 eye 13 diseases 14 are 15 expected 15 expected 16 to 15 expected 17 rise 16 to 17 rise 17 rise 18 in 18 in 21 years 19 the 21 years 20 coming 21 years these projections are primarily based upon population projections , [but] give little consideration to changes in health behaviors , racial/ethnic differences , environmental exposures , and changes in health care practices that may influence estimates of costs of actual health care burden . 0 ###LEFT-WALL### 2 projections 0 ###LEFT-WALL### 5 based 0 ###LEFT-WALL### 9 , 0 ###LEFT-WALL### 26 and 0 ###LEFT-WALL### 43 . 1 these 2 projections 2 projections 3 are 3 are 5 based 4 primarily 5 based 5 based 6 upon 6 upon 8 projections 7 population 8 projections 9 , 11 give 11 give 13 consideration 11 give 14 to 12 little 13 consideration 14 to 26 and 15 changes 16 in 15 changes 26 and 16 in 18 behaviors 17 health 18 behaviors 18 behaviors 21 differences 18 behaviors 24 exposures 19 , 21 differences 20 racial/ethnic 21 differences 21 differences 22 , 22 , 24 exposures 23 environmental 24 exposures 24 exposures 25 , 26 and 27 changes 26 and 28 in 28 in 31 practices 29 health 30 care 30 care 31 practices 31 practices 32 that 31 practices 34 influence 32 that 33 may 33 may 34 influence 34 influence 35 estimates 35 estimates 36 of 35 estimates 38 of 36 of 37 costs 38 of 42 burden 39 actual 41 care 40 health 41 care 41 care 42 burden conclusions : ongoing monitoring of trends in eye disease distribution is needed rather than projections based on old data that may be inadequate for generating reliable prediction models . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 29 . 2 : 4 monitoring 3 ongoing 4 monitoring 4 monitoring 5 of 4 monitoring 12 needed 4 monitoring 16 based 5 of 6 trends 6 trends 7 in 6 trends 10 distribution 6 trends 11 is 7 in 9 disease 8 eye 9 disease 10 distribution 11 is 12 needed 14 than 13 rather 14 than 14 than 15 projections 16 based 17 on 17 on 19 data 18 old 19 data 19 data 20 that 19 data 21 may 20 that 21 may 21 may 22 be 22 be 23 inadequate 23 inadequate 24 for 24 for 25 generating 25 generating 28 models 26 reliable 27 prediction 27 prediction 28 models there is a perpetual need to train new researchers with expertise in epidemiology , as the exigency for current prevalence estimates is crucial to maximize optimal visual health in the population . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 32 . 1 there 2 is 2 is 5 need 3 a 4 perpetual 3 a 5 need 4 perpetual 5 need 5 need 6 to 5 need 14 , 6 to 14 , 7 train 9 researchers 7 train 10 with 7 train 12 in 7 train 14 , 8 new 9 researchers 10 with 11 expertise 12 in 13 epidemiology 14 , 25 maximize 15 as 17 exigency 15 as 22 is 16 the 17 exigency 17 exigency 18 for 17 exigency 22 is 18 for 21 estimates 19 current 21 estimates 20 prevalence 21 estimates 22 is 23 crucial 23 crucial 24 to 24 to 25 maximize 25 maximize 28 health 26 optimal 28 health 27 visual 28 health 28 health 29 in 29 in 31 population 30 the 31 population this volume presents articles based on a workshop held june 14 to 16 , 2013 in rancho palos [verde] , ca sponsored by the ocular research symposia foundation ( orsf ) . 0 ###LEFT-WALL### 2 volume 0 ###LEFT-WALL### 3 presents 0 ###LEFT-WALL### 32 . 1 this 2 volume 2 volume 3 presents 3 presents 4 articles 3 presents 6 on 3 presents 12 to 4 articles 5 based 6 on 8 workshop 7 a 8 workshop 8 workshop 9 held 9 held 10 june 10 june 11 14 12 to 13 16 13 16 15 2013 13 16 21 ca 14 , 15 2013 15 2013 16 in 15 2013 20 , 16 in 18 palos 17 rancho 18 palos 20 , 21 ca 21 ca 22 sponsored 21 ca 23 by 21 ca 31 ) 23 by 30 orsf 24 the 30 orsf 25 ocular 26 research 26 research 27 symposia 27 symposia 28 foundation 28 foundation 30 orsf 29 ( 30 orsf the mission of the orsf is to focus attention on unmet needs and current research opportunities in eye research with the objective of accelerating translation of research findings to effective clinical care . 0 ###LEFT-WALL### 2 mission 0 ###LEFT-WALL### 6 is 0 ###LEFT-WALL### 33 . 1 the 2 mission 2 mission 3 of 2 mission 6 is 3 of 5 orsf 4 the 5 orsf 6 is 7 to 6 is 17 in 6 is 20 with 7 to 8 focus 8 focus 13 and 8 focus 15 research 9 attention 10 on 9 attention 13 and 10 on 12 needs 11 unmet 12 needs 13 and 14 current 13 and 15 research 15 research 16 opportunities 17 in 19 research 18 eye 19 research 20 with 22 objective 21 the 22 objective 22 objective 23 of 23 of 24 accelerating 24 accelerating 25 translation 24 accelerating 29 to 25 translation 26 of 26 of 28 findings 27 research 28 findings 29 to 32 care 30 effective 32 care 31 clinical 32 care in this workshop , the subject of the " [the] aging eye " was addressed , including the prevalence of eye diseases in aging and the economic burden imposed by these diseases . 0 ###LEFT-WALL### 6 subject 0 ###LEFT-WALL### 15 addressed 1 in 3 workshop 1 in 4 , 1 in 6 subject 2 this 3 workshop 5 the 6 subject 6 subject 7 of 6 subject 14 was 7 of 12 eye 8 the 9 " 8 the 12 eye 11 aging 12 eye 12 eye 13 " 14 was 15 addressed 15 addressed 17 including 16 , 17 including 17 including 25 and 17 including 30 by 17 including 33 . 18 the 25 and 19 prevalence 20 of 19 prevalence 25 and 20 of 22 diseases 21 eye 22 diseases 22 diseases 23 in 23 in 24 aging 25 and 28 burden 25 and 29 imposed 26 the 28 burden 27 economic 28 burden 30 by 32 diseases 31 these 32 diseases new research work was highlighted on the genetics , biology , biochemistry , neurochemistry , and the impact of nutrition and the environment [on] function in the older eye . 0 ###LEFT-WALL### 3 work 0 ###LEFT-WALL### 5 highlighted 0 ###LEFT-WALL### 30 . 1 new 3 work 2 research 3 work 3 work 4 was 4 was 5 highlighted 5 highlighted 6 on 5 highlighted 26 in 6 on 16 and 7 the 8 genetics 8 genetics 9 , 9 , 10 biology 9 , 11 , 11 , 12 biochemistry 11 , 13 , 13 , 14 neurochemistry 13 , 16 and 15 , 16 and 16 and 18 impact 16 and 19 of 17 the 18 impact 19 of 21 and 20 nutrition 21 and 21 and 25 function 22 the 25 function 23 environment 25 function 26 in 29 eye 27 the 29 eye 28 older 29 eye by identifying " low - hanging fruit " ( i.e [.] , the best opportunities for successful transition of laboratory research for the prevention [of] and new treatments and cures for ocular diseases ) [,] we seek to spur funding at both the basic research and clinical levels , resulting in sight - saving and sight - restoration measures in the near future . 0 ###LEFT-WALL### 4 low 1 by 2 identifying 1 by 4 low 2 identifying 3 " 4 low 6 hanging 4 low 15 opportunities 4 low 16 for 5 - 6 hanging 6 hanging 7 fruit 6 hanging 12 , 7 fruit 8 " 7 fruit 10 i.e 9 ( 10 i.e 10 i.e 12 , 13 the 14 best 13 the 15 opportunities 16 for 18 transition 17 successful 18 transition 18 transition 19 of 19 of 29 and 20 laboratory 21 research 21 research 22 for 21 research 26 and 22 for 24 prevention 23 the 24 prevention 26 and 28 treatments 26 and 29 and 27 new 28 treatments 29 and 30 cures 29 and 34 ) 29 and 36 we 29 and 39 spur 29 and 40 funding 30 cures 31 for 31 for 33 diseases 32 ocular 33 diseases 36 we 37 seek 37 seek 38 to 37 seek 39 spur 38 to 39 spur 40 funding 41 at 40 funding 46 and 40 funding 51 in 41 at 42 both 43 the 45 research 44 basic 45 research 45 research 46 and 46 and 48 levels 46 and 49 , 46 and 50 resulting 47 clinical 48 levels 49 , 50 resulting 51 in 52 sight 52 sight 55 and 53 - 55 and 54 saving 55 and 55 and 56 sight 55 and 57 - 55 and 58 restoration 55 and 59 measures 55 and 64 . 58 restoration 59 measures 59 measures 60 in 60 in 63 future 61 the 63 future 62 near 63 future during human brain development through infancy and childhood , microstructural and macrostructural changes take place to reshape the brain 's structural networks and better adapt them to sophisticated functional and cognitive requirements . 0 ###LEFT-WALL### 13 changes 0 ###LEFT-WALL### 23 and 0 ###LEFT-WALL### 33 . 1 during 4 development 1 during 13 changes 2 human 4 development 3 brain 4 development 4 development 5 through 5 through 7 and 6 infancy 7 and 7 and 8 childhood 7 and 9 , 10 microstructural 11 and 11 and 12 macrostructural 11 and 13 changes 13 changes 23 and 14 take 15 place 14 take 16 to 14 take 23 and 16 to 17 reshape 17 reshape 22 networks 18 the 19 brain 19 brain 20 's 20 's 22 networks 21 structural 22 networks 23 and 25 adapt 23 and 27 to 24 better 25 adapt 25 adapt 26 them 27 to 32 requirements 28 sophisticated 32 requirements 29 functional 30 and 30 and 31 cognitive 30 and 32 requirements however , structural topological configuration [of] [the] human brain during this specific development period is not well understood . 0 ###LEFT-WALL### 9 brain 0 ###LEFT-WALL### 15 is 0 ###LEFT-WALL### 19 . 1 however 2 , 1 however 9 brain 3 structural 5 configuration 4 topological 5 configuration 5 configuration 9 brain 8 human 9 brain 9 brain 10 during 9 brain 15 is 10 during 14 period 11 this 12 specific 12 specific 13 development 13 development 14 period 15 is 16 not 15 is 17 well 17 well 18 understood modular organization and small - world attributes are evident at birth with several important topological metrics increasing monotonically during development . 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 8 are 0 ###LEFT-WALL### 21 . 1 modular 2 organization 2 organization 3 and 3 and 7 attributes 3 and 8 are 4 small 5 - 4 small 6 world 6 world 7 attributes 8 are 9 evident 9 evident 10 at 10 at 11 birth 11 birth 12 with 11 birth 17 increasing 11 birth 19 during 12 with 16 metrics 13 several 16 metrics 14 important 16 metrics 15 topological 16 metrics 17 increasing 18 monotonically 19 during 20 development most significant increases of regional nodes occur in the posterior cingulate cortex , which plays a pivotal role in the functional default mode network . 0 ###LEFT-WALL### 3 increases 0 ###LEFT-WALL### 7 occur 0 ###LEFT-WALL### 13 , 0 ###LEFT-WALL### 25 . 1 most 2 significant 2 significant 3 increases 3 increases 4 of 3 increases 7 occur 4 of 6 nodes 5 regional 6 nodes 7 occur 8 in 8 in 12 cortex 9 the 12 cortex 10 posterior 12 cortex 11 cingulate 12 cortex 13 , 14 which 13 , 15 plays 14 which 15 plays 15 plays 18 role 15 plays 19 in 16 a 17 pivotal 16 a 18 role 17 pivotal 18 role 19 in 24 network 20 the 24 network 21 functional 22 default 22 default 24 network 23 mode 24 network positive correlations exist between nodal efficiencies and fractional anisotropy of the white matter traced from these nodes , while correlation slopes vary among the brain regions . 0 ###LEFT-WALL### 2 correlations 0 ###LEFT-WALL### 3 exist 0 ###LEFT-WALL### 27 . 1 positive 2 correlations 2 correlations 3 exist 3 exist 4 between 3 exist 19 while 3 exist 23 among 4 between 7 and 5 nodal 6 efficiencies 6 efficiencies 7 and 7 and 9 anisotropy 7 and 18 , 8 fractional 9 anisotropy 9 anisotropy 10 of 10 of 13 matter 11 the 13 matter 12 white 13 matter 13 matter 14 traced 13 matter 15 from 15 from 17 nodes 16 these 17 nodes 19 while 21 slopes 19 while 22 vary 20 correlation 21 slopes 21 slopes 22 vary 23 among 26 regions 24 the 26 regions 25 brain 26 regions these results reveal substantial topological reorganization of human brain structural networks through infancy and childhood , which is likely to be the outcome of both heterogeneous strengthening of the major white matter tracts and pruning of other axonal fibers . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 reveal 0 ###LEFT-WALL### 40 . 1 these 2 results 2 results 3 reveal 3 reveal 6 reorganization 3 reveal 12 through 4 substantial 6 reorganization 5 topological 6 reorganization 6 reorganization 7 of 7 of 11 networks 8 human 9 brain 9 brain 11 networks 10 structural 11 networks 12 through 14 and 13 infancy 14 and 14 and 15 childhood 14 and 16 , 14 and 17 which 14 and 18 is 17 which 18 is 18 is 19 likely 19 likely 20 to 19 likely 21 be 20 to 21 be 21 be 23 outcome 22 the 23 outcome 23 outcome 24 of 24 of 25 both 25 both 26 heterogeneous 26 heterogeneous 34 and 27 strengthening 28 of 27 strengthening 34 and 28 of 33 tracts 29 the 33 tracts 30 major 32 matter 31 white 32 matter 32 matter 33 tracts 34 and 35 pruning 35 pruning 36 of 36 of 39 fibers 37 other 39 fibers 38 axonal 39 fibers this review focuses on 3 allergic disorders of persons coming up against venerable age : asthma , allergic rhinitis , and atopic dermatitis . 0 ###LEFT-WALL### 2 review 0 ###LEFT-WALL### 3 focuses 0 ###LEFT-WALL### 15 : 1 this 2 review 2 review 3 focuses 3 focuses 4 on 3 focuses 11 up 3 focuses 12 against 4 on 7 disorders 5 3 7 disorders 6 allergic 7 disorders 7 disorders 8 of 8 of 9 persons 9 persons 10 coming 12 against 14 age 13 venerable 14 age 15 : 21 and 15 : 24 . 16 asthma 17 , 17 , 19 rhinitis 17 , 21 and 18 allergic 19 rhinitis 20 , 21 and 21 and 23 dermatitis 22 atopic 23 dermatitis the prevalence of allergic diseases in the elderly ranges from 5 to 10 % and appears to be rising . 0 ###LEFT-WALL### 2 prevalence 0 ###LEFT-WALL### 15 and 0 ###LEFT-WALL### 20 . 1 the 2 prevalence 2 prevalence 3 of 2 prevalence 15 and 3 of 5 diseases 4 allergic 5 diseases 5 diseases 6 in 6 in 8 elderly 7 the 8 elderly 9 ranges 10 from 9 ranges 15 and 10 from 14 % 11 5 12 to 12 to 13 10 12 to 14 % 15 and 16 appears 16 appears 17 to 16 appears 18 be 17 to 18 be 18 be 19 rising a gradual decline [in] immune function , termed immunosenescence , and age - related changes in tissue structure influence the development of these disorders . 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 19 influence 0 ###LEFT-WALL### 25 . 1 a 6 function 2 gradual 3 decline 3 decline 6 function 5 immune 6 function 6 function 7 , 7 , 9 immunosenescence 7 , 11 and 8 termed 9 immunosenescence 10 , 11 and 11 and 12 age 11 and 19 influence 13 - 14 related 14 related 15 changes 14 related 16 in 14 related 19 influence 16 in 18 structure 17 tissue 18 structure 19 influence 21 development 20 the 21 development 21 development 22 of 22 of 24 disorders 23 these 24 disorders common complications are comorbidities , polypharmacy , and adverse effects of drugs . 0 ###LEFT-WALL### 2 complications 0 ###LEFT-WALL### 3 are 0 ###LEFT-WALL### 13 . 1 common 2 complications 2 complications 3 are 3 are 8 and 4 comorbidities 5 , 5 , 6 polypharmacy 5 , 8 and 7 , 8 and 8 and 10 effects 8 and 11 of 9 adverse 10 effects 11 of 12 drugs the elderly have difficulty mounting protective immune responses against newly encountered antigens . 0 ###LEFT-WALL### 2 elderly 0 ###LEFT-WALL### 3 have 0 ###LEFT-WALL### 13 . 1 the 2 elderly 2 elderly 3 have 3 have 4 difficulty 4 difficulty 5 mounting 5 mounting 8 responses 5 mounting 9 against 6 protective 8 responses 7 immune 8 responses 9 against 12 antigens 10 newly 11 encountered 11 encountered 12 antigens the integrity of epithelial barriers [is] compromised , leading to a chronic , subclinical inflammatory state and an enhanced th2 [(] allergic ) immune response . 0 ###LEFT-WALL### 2 integrity 0 ###LEFT-WALL### 7 compromised 1 the 2 integrity 2 integrity 3 of 2 integrity 7 compromised 3 of 5 barriers 4 epithelial 5 barriers 7 compromised 9 leading 8 , 9 leading 9 leading 10 to 9 leading 26 . 10 to 25 response 11 a 25 response 12 chronic 13 , 13 , 16 state 13 , 17 and 14 subclinical 16 state 15 inflammatory 16 state 17 and 20 th2 17 and 25 response 18 an 20 th2 19 enhanced 20 th2 22 allergic 23 ) 22 allergic 25 response 24 immune 25 response undiagnosed asthma is frequent in elderly persons ( about 8 % ) and still more commonplace in those with respiratory symptoms . 0 ###LEFT-WALL### 2 asthma 0 ###LEFT-WALL### 3 is 0 ###LEFT-WALL### 22 . 1 undiagnosed 2 asthma 2 asthma 3 is 3 is 13 and 4 frequent 5 in 4 frequent 9 about 4 frequent 13 and 5 in 7 persons 6 elderly 7 persons 8 ( 9 about 9 about 11 % 9 about 12 ) 10 8 11 % 13 and 14 still 13 and 16 commonplace 15 more 16 commonplace 16 commonplace 17 in 16 commonplace 19 with 17 in 18 those 19 with 21 symptoms 20 respiratory 21 symptoms poorly controlled asthma in the elderly undermines their functional status and leads to a loss of autonomy and social isolation that may delay seeking medical services . 0 ###LEFT-WALL### 3 asthma 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 27 . 1 poorly 3 asthma 2 controlled 3 asthma 3 asthma 4 in 3 asthma 11 and 4 in 6 elderly 5 the 6 elderly 7 undermines 10 status 7 undermines 11 and 8 their 10 status 9 functional 10 status 11 and 12 leads 11 and 13 to 13 to 18 and 14 a 15 loss 15 loss 16 of 15 loss 18 and 16 of 17 autonomy 18 and 20 isolation 18 and 21 that 18 and 22 may 18 and 24 seeking 19 social 20 isolation 21 that 22 may 22 may 23 delay 24 seeking 26 services 25 medical 26 services aggravation of allergic rhinitis coincides with exacerbation of asthma , whereas treatment of nasal inflammation improves control of the asthma . 0 ###LEFT-WALL### 1 aggravation 0 ###LEFT-WALL### 16 improves 0 ###LEFT-WALL### 21 . 1 aggravation 2 of 1 aggravation 5 coincides 2 of 4 rhinitis 3 allergic 4 rhinitis 5 coincides 6 with 5 coincides 11 whereas 6 with 7 exacerbation 7 exacerbation 8 of 8 of 9 asthma 10 , 11 whereas 11 whereas 12 treatment 12 treatment 13 of 12 treatment 16 improves 13 of 15 inflammation 14 nasal 15 inflammation 16 improves 17 control 17 control 18 of 18 of 20 asthma 19 the 20 asthma atopic [dermatitis] is a chronically relapsing inflammatory skin disease often associated [with] respiratory allergy . 0 ###LEFT-WALL### 1 atopic 0 ###LEFT-WALL### 3 is 0 ###LEFT-WALL### 15 . 1 atopic 3 is 3 is 14 allergy 4 a 5 chronically 4 a 14 allergy 5 chronically 6 relapsing 6 relapsing 8 skin 7 inflammatory 8 skin 8 skin 9 disease 9 disease 11 associated 10 often 11 associated 13 respiratory 14 allergy [given] the importance of gamma oscillations in normal and disturbed cognition , there has been growing interest in their developmental trajectory . 0 ###LEFT-WALL### 3 importance 0 ###LEFT-WALL### 15 been 0 ###LEFT-WALL### 22 . 2 the 3 importance 3 importance 4 of 3 importance 14 has 4 of 6 oscillations 5 gamma 6 oscillations 6 oscillations 7 in 6 oscillations 13 there 7 in 9 and 8 normal 9 and 9 and 11 cognition 9 and 12 , 10 disturbed 11 cognition 14 has 15 been 15 been 16 growing 16 growing 17 interest 16 growing 18 in 18 in 21 trajectory 19 their 21 trajectory 20 developmental 21 trajectory in the current study , age - related changes in sensory cortical gamma were studied using the auditory steady - state response ( assr ) , indexing cortical activity entrained to a periodic auditory stimulus . 0 ###LEFT-WALL### 9 changes 0 ###LEFT-WALL### 15 studied 1 in 4 study 1 in 7 - 1 in 9 changes 2 the 4 study 3 current 4 study 4 study 6 age 5 , 6 age 6 age 7 - 8 related 9 changes 9 changes 10 in 9 changes 14 were 10 in 13 gamma 11 sensory 13 gamma 12 cortical 13 gamma 14 were 15 studied 15 studied 16 using 16 using 22 response 17 the 22 response 18 auditory 21 state 19 steady 20 - 19 steady 21 state 21 state 22 response 22 response 24 assr 22 response 27 indexing 23 ( 24 assr 24 assr 25 ) 26 , 27 indexing 27 indexing 29 activity 27 indexing 31 to 27 indexing 36 . 28 cortical 29 activity 29 activity 30 entrained 31 to 35 stimulus 32 a 33 periodic 32 a 35 stimulus 33 periodic 35 stimulus 34 auditory 35 stimulus a large sample ( n = 188 ) aged 8 - 22 years had electroencephalography recording of assr during 20 - [,] 30 - , and 40 [-] hz click trains , analyzed for evoked amplitude , phase [-] locking factor ( plf ) and cross - frequency coupling ( cfc [ )(with lower frequency oscillations . 0 ###LEFT-WALL### 3 sample 0 ###LEFT-WALL### 9 aged 0 ###LEFT-WALL### 11 - 1 a 2 large 1 a 3 sample 2 large 3 sample 3 sample 6 = 3 sample 9 aged 4 ( 6 = 5 n 6 = 6 = 7 188 6 = 8 ) 9 aged 10 8 11 - 13 years 11 - 14 had 12 22 13 years 13 years 14 had 14 had 16 recording 15 electroencephalography 16 recording 16 recording 17 of 17 of 26 and 18 assr 19 during 18 assr 26 and 19 during 20 20 20 20 23 30 21 - 23 30 23 30 24 - 25 , 26 and 26 and 31 trains 26 and 32 , 26 and 33 analyzed 26 and 34 for 27 40 29 hz 29 hz 30 click 30 click 31 trains 34 for 45 and 35 evoked 36 amplitude 36 amplitude 37 , 37 , 38 phase 37 , 45 and 38 phase 40 locking 40 locking 41 factor 41 factor 43 plf 42 ( 43 plf 43 plf 44 ) 45 and 46 cross 45 and 49 coupling 47 - 49 coupling 48 frequency 49 coupling 49 coupling 51 cfc 49 coupling 57 . 50 ( 51 cfc 51 cfc 53 )(with 51 cfc 57 . 53 )(with 56 oscillations 54 lower 55 frequency 55 frequency 56 oscillations both 40 [-] hz evoked power and plf increased monotonically from 8 through 16 years , and subsequently decreased toward ages 20 - 22 years . 0 ###LEFT-WALL### 7 and 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 23 - 0 ###LEFT-WALL### 26 . 1 both 7 and 2 40 4 hz 4 hz 5 evoked 5 evoked 6 power 6 power 7 and 7 and 8 plf 7 and 17 and 9 increased 10 monotonically 9 increased 11 from 9 increased 17 and 11 from 15 years 12 8 15 years 13 through 15 years 14 16 15 years 16 , 17 and 17 and 19 decreased 17 and 20 toward 18 subsequently 19 decreased 20 toward 21 ages 21 ages 22 20 23 - 25 years 24 22 25 years cfc followed a similar pattern , with [strongest] age - related modulation of 40 [-] hz amplitude by the phase of delta oscillations . 0 ###LEFT-WALL### 1 cfc 0 ###LEFT-WALL### 2 followed 0 ###LEFT-WALL### 11 related 1 cfc 2 followed 2 followed 5 pattern 3 a 4 similar 3 a 5 pattern 4 similar 5 pattern 5 pattern 7 with 6 , 7 with 7 with 9 age 7 with 10 - 10 - 11 related 11 related 12 modulation 11 related 18 by 11 related 24 . 12 modulation 13 of 13 of 17 amplitude 14 40 16 hz 16 hz 17 amplitude 18 by 20 phase 19 the 20 phase 20 phase 21 of 21 of 23 oscillations 22 delta 23 oscillations in contrast , the evoked power , plf and cfc for the 20 - and 30 [-] hz stimulation were distinct from the 40 - [hz] condition , with flat or decreasing profiles from childhood to early adulthood . 0 ###LEFT-WALL### 15 and 0 ###LEFT-WALL### 20 were 0 ###LEFT-WALL### 39 . 1 in 2 contrast 1 in 15 and 2 contrast 6 power 3 , 6 power 4 the 6 power 5 evoked 6 power 6 power 7 , 8 plf 9 and 9 and 10 cfc 10 cfc 11 for 10 cfc 15 and 11 for 13 20 12 the 13 20 14 - 15 and 15 and 19 stimulation 15 and 20 were 16 30 18 hz 18 hz 19 stimulation 20 were 21 distinct 21 distinct 22 from 21 distinct 29 with 22 from 24 40 23 the 24 40 24 40 27 condition 25 - 27 condition 27 condition 28 , 29 with 33 profiles 30 flat 31 or 31 or 32 decreasing 31 or 33 profiles 33 profiles 34 from 34 from 35 childhood 35 childhood 36 to 36 to 38 adulthood 37 early 38 adulthood the inverted [u] [-] shaped developmental trajectory of gamma oscillations may be consistent with interacting maturational processes - such as increasing fast gaba inhibition that enhances gamma activity and synaptic pruning that decreases gamma activity - that may continue from childhood through to adulthood . 0 ###LEFT-WALL### 7 trajectory 0 ###LEFT-WALL### 12 be 0 ###LEFT-WALL### 18 - 1 the 7 trajectory 2 inverted 7 trajectory 5 shaped 7 trajectory 6 developmental 7 trajectory 7 trajectory 8 of 7 trajectory 11 may 8 of 10 oscillations 9 gamma 10 oscillations 11 may 12 be 12 be 13 consistent 13 consistent 14 with 14 with 17 processes 15 interacting 17 processes 16 maturational 17 processes 18 - 24 inhibition 18 - 33 decreases 18 - 36 - 19 such 24 inhibition 20 as 21 increasing 21 increasing 22 fast 22 fast 24 inhibition 23 gaba 24 inhibition 24 inhibition 25 that 24 inhibition 26 enhances 24 inhibition 33 decreases 25 that 26 enhances 26 enhances 29 and 27 gamma 28 activity 28 activity 29 and 29 and 30 synaptic 29 and 31 pruning 31 pruning 32 that 33 decreases 35 activity 34 gamma 35 activity 36 - 37 that 36 - 39 continue 36 - 45 . 37 that 38 may 38 may 39 continue 39 continue 40 from 39 continue 42 through 40 from 41 childhood 42 through 43 to 43 to 44 adulthood background/aims : a deficit of various hormones during the process of aging and/or a heightened inflammatory state may be causally linked to the development of frailty . 0 ###LEFT-WALL### 1 background/aims 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 21 linked 0 ###LEFT-WALL### 27 . 2 : 4 deficit 3 a 4 deficit 4 deficit 5 of 5 of 7 hormones 6 various 7 hormones 7 hormones 8 during 8 during 10 process 9 the 10 process 10 process 11 of 11 of 12 aging 12 aging 13 and/or 13 and/or 17 state 14 a 17 state 15 heightened 17 state 16 inflammatory 17 state 17 state 18 may 18 may 19 be 19 be 20 causally 19 be 21 linked 21 linked 22 to 22 to 24 development 23 the 24 development 24 development 25 of 25 of 26 frailty phytoestrogens as weak estrogens , antioxidants , and anti - inflammatory agents may counteract this process . 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 14 counteract 0 ###LEFT-WALL### 17 . 1 phytoestrogens 2 as 1 phytoestrogens 5 , 2 as 4 estrogens 3 weak 4 estrogens 5 , 6 antioxidants 5 , 8 and 7 , 8 and 8 and 12 agents 8 and 13 may 9 anti 10 - 9 anti 12 agents 11 inflammatory 12 agents 13 may 14 counteract 14 counteract 16 process 15 this 16 process methods : in a cross - sectional study including two cycles of the national health and nutrition examination survey ( nhanes , i.e [.] 1999 - 2002 ) , logistic regression was used to analyze the association between urinary concentrations of isoflavones and lignans and frailty in 600 females aged 50 years or older ( median age 66.5 years ) . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 61 . 1 methods 2 : 2 : 3 in 3 in 5 cross 4 a 5 cross 5 cross 8 study 6 - 8 study 7 sectional 8 study 8 study 9 including 8 study 60 ) 9 including 11 cycles 9 including 34 to 10 two 11 cycles 11 cycles 12 of 12 of 17 nutrition 13 the 17 nutrition 14 national 15 health 15 health 16 and 16 and 17 nutrition 17 nutrition 31 regression 17 nutrition 32 was 17 nutrition 33 used 18 examination 19 survey 19 survey 21 nhanes 19 survey 31 regression 20 ( 21 nhanes 21 nhanes 23 i.e 21 nhanes 29 , 22 , 23 i.e 23 i.e 26 - 23 i.e 28 ) 25 1999 26 - 26 - 27 2002 30 logistic 31 regression 31 regression 32 was 34 to 35 analyze 35 analyze 45 and 35 analyze 47 in 36 the 37 association 37 association 38 between 37 association 41 of 37 association 45 and 38 between 40 concentrations 39 urinary 40 concentrations 41 of 43 and 42 isoflavones 43 and 43 and 44 lignans 45 and 46 frailty 47 in 48 600 48 600 49 females 48 600 50 aged 48 600 59 years 49 females 50 aged 50 aged 53 or 51 50 52 years 52 years 53 or 53 or 54 older 55 ( 59 years 56 median 57 age 57 age 59 years 58 66.5 59 years 59 years 60 ) participants were classified as ['] frail ['] [(] meeting 3 or more of the 5 frailty criteria ) , ['] prefrail ['] ( meeting 1 or 2 of the criteria ) , or ['] robust ['] ( meeting none of the criteria ) . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 2 were 0 ###LEFT-WALL### 44 . 1 participants 2 were 2 were 33 or 3 classified 9 meeting 4 as 6 frail 6 frail 9 meeting 9 meeting 10 3 9 meeting 11 or 11 or 17 criteria 11 or 18 ) 11 or 21 prefrail 11 or 33 or 12 more 13 of 12 more 17 criteria 13 of 15 5 14 the 15 5 16 frailty 17 criteria 19 , 21 prefrail 21 prefrail 24 meeting 21 prefrail 32 , 23 ( 24 meeting 24 meeting 26 or 24 meeting 31 ) 25 1 26 or 26 or 27 2 26 or 28 of 28 of 30 criteria 29 the 30 criteria 33 or 35 robust 33 or 38 meeting 37 ( 38 meeting 38 meeting 39 none 38 meeting 43 ) 39 none 40 of 40 of 42 criteria 41 the 42 criteria four percent were frail . 0 ###LEFT-WALL### 2 percent 0 ###LEFT-WALL### 3 were 0 ###LEFT-WALL### 5 . 1 four 2 percent 2 percent 3 were 3 were 4 frail results : for all of the phytoestrogens considered , the unadjusted or were lower than 1 but generally not statistically significant aside from the association with o - desmethylangolensin ( o - dma ) [(] or = 0.76 [;] 95 % ci 0.61 - 0.92 ) . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 47 . 2 : 12 or 2 : 13 were 2 : 17 but 3 for 4 all 3 for 9 , 3 for 12 or 4 all 5 of 5 of 7 phytoestrogens 6 the 7 phytoestrogens 7 phytoestrogens 8 considered 10 the 12 or 11 unadjusted 12 or 12 or 13 were 13 were 14 lower 14 lower 15 than 15 than 16 1 17 but 36 or 17 but 37 = 18 generally 36 or 19 not 21 significant 19 not 36 or 20 statistically 21 significant 21 significant 22 aside 21 significant 23 from 23 from 25 association 24 the 25 association 25 association 26 with 25 association 29 desmethylangolensin 26 with 27 o 28 - 29 desmethylangolensin 29 desmethylangolensin 32 - 29 desmethylangolensin 34 ) 30 ( 32 - 31 o 32 - 32 - 33 dma 32 - 34 ) 36 or 37 = 37 = 42 ci 38 0.76 42 ci 40 95 42 ci 41 % 42 ci 42 ci 43 0.61 42 ci 45 0.92 44 - 45 0.92 45 0.92 46 ) multivariate analysis did not attenuate this finding ( or [=] 0.74 [;] 95 % ci 0.61 - 0.90 ) . 0 ###LEFT-WALL### 2 analysis 0 ###LEFT-WALL### 5 attenuate 0 ###LEFT-WALL### 20 . 1 multivariate 2 analysis 2 analysis 3 did 3 did 4 not 3 did 5 attenuate 5 attenuate 7 finding 6 this 7 finding 7 finding 15 ci 8 ( 15 ci 9 or 11 0.74 9 or 15 ci 13 95 15 ci 14 % 15 ci 15 ci 17 - 15 ci 19 ) 16 0.61 17 - 17 - 18 0.90 conclusions : this first analysis of the relationship between phytoestrogens and frailty revealed an inverse association between urinary [o] - dma levels and frailty in women . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 27 . 2 : 11 and 2 : 13 revealed 3 this 5 analysis 4 first 5 analysis 5 analysis 6 of 5 analysis 9 between 5 analysis 11 and 6 of 8 relationship 7 the 8 relationship 9 between 10 phytoestrogens 11 and 12 frailty 11 and 13 revealed 13 revealed 16 association 13 revealed 17 between 13 revealed 25 in 14 an 15 inverse 14 an 16 association 15 inverse 16 association 17 between 23 and 18 urinary 20 - 18 urinary 22 levels 21 dma 22 levels 22 levels 23 and 23 and 24 frailty 25 in 26 women however , the number of frail women was low . 0 ###LEFT-WALL### 4 number 0 ###LEFT-WALL### 8 was 0 ###LEFT-WALL### 10 . 1 however 2 , 1 however 4 number 3 the 4 number 4 number 5 of 4 number 8 was 5 of 7 women 6 frail 7 women 8 was 9 low although this finding may be confounded or biased , it seems worthwhile to intensify research on the potential preventive effects of o - dma . 0 ###LEFT-WALL### 10 it 0 ###LEFT-WALL### 11 seems 0 ###LEFT-WALL### 23 - 0 ###LEFT-WALL### 25 . 1 although 3 finding 1 although 7 or 1 although 9 , 1 although 10 it 2 this 3 finding 3 finding 7 or 4 may 5 be 4 may 7 or 5 be 6 confounded 7 or 8 biased 10 it 11 seems 11 seems 12 worthwhile 12 worthwhile 13 to 12 worthwhile 16 on 13 to 14 intensify 14 intensify 15 research 16 on 20 effects 17 the 20 effects 18 potential 20 effects 19 preventive 20 effects 20 effects 21 of 21 of 22 o 23 - 24 dma previous studies have demonstrated a therapeutic benefit of pharmaceutical pgc - 1α activation in cellular and murine model of disorders linked to mitochondrial dysfunction . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 4 demonstrated 0 ###LEFT-WALL### 11 - 0 ###LEFT-WALL### 12 1α 0 ###LEFT-WALL### 25 . 1 previous 2 studies 2 studies 3 have 3 have 4 demonstrated 4 demonstrated 7 benefit 5 a 6 therapeutic 5 a 7 benefit 6 therapeutic 7 benefit 7 benefit 8 of 8 of 10 pgc 9 pharmaceutical 10 pgc 11 - 12 1α 12 1α 13 activation 12 1α 14 in 14 in 16 and 15 cellular 16 and 16 and 18 model 16 and 19 of 17 murine 18 model 19 of 20 disorders 20 disorders 21 linked 21 linked 22 to 22 to 24 dysfunction 23 mitochondrial 24 dysfunction while in some cases , this effect seems to be clearly associated with boosting of mitochondrial [function] , additional alterations as well as tissue - and cell - type - specific effects might play an important role . 0 ###LEFT-WALL### 32 effects 0 ###LEFT-WALL### 34 play 0 ###LEFT-WALL### 38 . 1 while 7 effect 1 while 8 seems 1 while 32 effects 2 in 4 cases 2 in 5 , 2 in 7 effect 3 some 4 cases 6 this 7 effect 7 effect 8 seems 8 seems 9 to 8 seems 12 associated 9 to 10 be 10 be 11 clearly 10 be 12 associated 12 associated 13 with 12 associated 22 well 13 with 14 boosting 14 boosting 15 of 15 of 20 alterations 16 mitochondrial 18 , 16 mitochondrial 20 alterations 19 additional 20 alterations 21 as 22 well 23 as 26 and 23 as 29 type 23 as 30 - 23 as 32 effects 24 tissue 26 and 25 - 26 and 26 and 27 cell 26 and 28 - 26 and 29 type 31 specific 32 effects 32 effects 33 might 33 might 34 play 34 play 37 role 35 an 36 important 35 an 37 role 36 important 37 role we initiated a comprehensive analysis of the effects of potential pgc - 1α - activating drugs and pharmaceutically targeted the ppar ( bezafibrate , rosiglitazone ) , ampk ( aicar , metformin ) and sirt1 ( resveratrol ) pathways in hela cells , neuronal cells and pgc - 1α - deficient mefs to get insight into cell type specificity and pgc - 1α dependence of their working action . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 initiated 0 ###LEFT-WALL### 69 . 1 we 2 initiated 2 initiated 39 pathways 2 initiated 40 in 3 a 4 comprehensive 3 a 5 analysis 4 comprehensive 5 analysis 5 analysis 6 of 5 analysis 9 of 5 analysis 27 , 6 of 8 effects 7 the 8 effects 9 of 15 activating 10 potential 15 activating 11 pgc 13 1α 11 pgc 15 activating 12 - 13 1α 13 1α 14 - 15 activating 17 and 16 drugs 17 and 17 and 19 targeted 17 and 21 ppar 18 pharmaceutically 19 targeted 20 the 21 ppar 21 ppar 25 rosiglitazone 22 ( 25 rosiglitazone 23 bezafibrate 24 , 23 bezafibrate 25 rosiglitazone 25 rosiglitazone 26 ) 27 , 28 ampk 27 , 34 and 28 ampk 30 aicar 29 ( 30 aicar 30 aicar 32 metformin 30 aicar 33 ) 31 , 32 metformin 32 metformin 33 ) 34 and 35 sirt1 34 and 39 pathways 35 sirt1 37 resveratrol 36 ( 37 resveratrol 37 resveratrol 38 ) 40 in 46 and 41 hela 42 cells 42 cells 43 , 43 , 45 cells 43 , 46 and 44 neuronal 45 cells 46 and 64 dependence 47 pgc 49 1α 47 pgc 63 1α 48 - 49 1α 49 1α 52 mefs 49 1α 62 - 50 - 52 mefs 51 deficient 52 mefs 52 mefs 53 to 52 mefs 54 get 52 mefs 62 - 53 to 54 get 54 get 55 insight 54 get 56 into 56 into 60 and 57 cell 59 specificity 58 type 59 specificity 59 specificity 60 and 60 and 61 pgc 63 1α 64 dependence 64 dependence 65 of 65 of 67 working 66 their 67 working 67 working 68 action we used bezafibrate as a model drug to assess the effect on a tissue - specific level in a murine model . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 used 0 ###LEFT-WALL### 15 - 0 ###LEFT-WALL### 22 . 1 we 2 used 2 used 3 bezafibrate 2 used 4 as 2 used 8 to 2 used 9 assess 4 as 7 drug 5 a 7 drug 6 model 7 drug 8 to 9 assess 9 assess 11 effect 9 assess 12 on 10 the 11 effect 12 on 14 tissue 13 a 14 tissue 15 - 17 level 16 specific 17 level 17 level 18 in 18 in 21 model 19 a 21 model 20 murine 21 model not all analyzed drugs activate the pgc pathway or alter mitochondrial protein levels . 0 ###LEFT-WALL### 4 drugs 0 ###LEFT-WALL### 9 or 0 ###LEFT-WALL### 14 . 1 not 2 all 2 all 4 drugs 3 analyzed 4 drugs 4 drugs 9 or 5 activate 8 pathway 5 activate 9 or 6 the 8 pathway 7 pgc 8 pathway 9 or 10 alter 9 or 13 levels 10 alter 12 protein 11 mitochondrial 12 protein however , they all affect supramolecular assembly [of] oxphos complexes and oxphos protein stability . 0 ###LEFT-WALL### 3 they 0 ###LEFT-WALL### 5 affect 0 ###LEFT-WALL### 15 . 1 however 2 , 1 however 3 they 3 they 5 affect 4 all 5 affect 5 affect 14 stability 6 supramolecular 7 assembly 7 assembly 14 stability 9 oxphos 14 stability 10 complexes 11 and 11 and 12 oxphos 11 and 14 stability 13 protein 14 stability in addition , a clear drug - and cell - type - specific influence on several cellular stress pathways as well as on post - translational modifications could be demonstrated , which might be relevant to fully understand the action of the analyzed drugs in the disease state . 0 ###LEFT-WALL### 11 type 0 ###LEFT-WALL### 12 - 0 ###LEFT-WALL### 49 . 1 in 8 and 1 in 10 - 1 in 11 type 2 addition 3 , 3 , 6 drug 3 , 8 and 4 a 5 clear 4 a 6 drug 5 clear 6 drug 7 - 8 and 8 and 9 cell 12 - 14 influence 13 specific 14 influence 14 influence 15 on 15 on 19 pathways 16 several 19 pathways 17 cellular 19 pathways 18 stress 19 pathways 19 pathways 20 as 19 pathways 32 which 19 pathways 33 might 20 as 21 well 21 well 30 demonstrated 22 as 27 modifications 22 as 30 demonstrated 23 on 24 post 23 on 25 - 23 on 27 modifications 26 translational 27 modifications 27 modifications 28 could 28 could 29 be 29 be 30 demonstrated 30 demonstrated 31 , 32 which 33 might 33 might 34 be 34 be 35 relevant 35 relevant 36 to 35 relevant 38 understand 36 to 38 understand 37 fully 38 understand 38 understand 40 action 38 understand 45 in 39 the 40 action 40 action 41 of 41 of 44 drugs 42 the 44 drugs 43 analyzed 44 drugs 45 in 48 state 46 the 48 state 47 disease 48 state importantly , the effect on the activation of mitochondrial biogenesis and stress response program upon drug treatment is pgc - 1α dependent in mefs demonstrating not only the pleiotropic effects of this molecule but points also to the working mechanism of the analyzed drugs . 0 ###LEFT-WALL### 4 effect 0 ###LEFT-WALL### 18 is 0 ###LEFT-WALL### 20 - 0 ###LEFT-WALL### 45 . 1 importantly 2 , 1 importantly 4 effect 3 the 4 effect 4 effect 5 on 4 effect 8 of 4 effect 18 is 5 on 7 activation 6 the 7 activation 8 of 11 and 9 mitochondrial 10 biogenesis 10 biogenesis 11 and 11 and 14 program 11 and 15 upon 12 stress 14 program 13 response 14 program 15 upon 17 treatment 16 drug 17 treatment 18 is 19 pgc 20 - 21 1α 21 1α 22 dependent 21 1α 25 demonstrating 22 dependent 23 in 23 in 24 mefs 25 demonstrating 34 but 25 demonstrating 36 also 25 demonstrating 37 to 26 not 27 only 27 only 34 but 28 the 30 effects 29 pleiotropic 30 effects 30 effects 31 of 30 effects 34 but 31 of 33 molecule 32 this 33 molecule 34 but 35 points 37 to 40 mechanism 38 the 40 mechanism 39 working 40 mechanism 40 mechanism 41 of 41 of 44 drugs 42 the 44 drugs 43 analyzed 44 drugs the definition of the action spectrum of the different drugs forms the basis for a defect - specific compensation strategy and a future personalized therapeutic approach . 0 ###LEFT-WALL### 2 definition 0 ###LEFT-WALL### 11 forms 0 ###LEFT-WALL### 17 - 1 the 2 definition 2 definition 3 of 2 definition 11 forms 3 of 6 spectrum 4 the 6 spectrum 5 action 6 spectrum 6 spectrum 7 of 7 of 10 drugs 8 the 10 drugs 9 different 10 drugs 11 forms 13 basis 11 forms 14 for 12 the 13 basis 14 for 16 defect 15 a 16 defect 17 - 21 and 17 - 26 approach 17 - 27 . 18 specific 19 compensation 19 compensation 20 strategy 20 strategy 21 and 21 and 23 future 21 and 24 personalized 21 and 26 approach 22 a 23 future 24 personalized 25 therapeutic the hallmarks of sporadic alzheimer 's disease ( ad ) are extracellular amyloid deposits , intracellular neurofibrillary tangles ( nfts [ )(, and neuronal death . 0 ###LEFT-WALL### 2 hallmarks 0 ###LEFT-WALL### 11 are 1 the 2 hallmarks 2 hallmarks 3 of 2 hallmarks 11 are 3 of 7 disease 4 sporadic 5 alzheimer 5 alzheimer 6 's 6 's 7 disease 7 disease 9 ad 8 ( 9 ad 9 ad 10 ) 11 are 14 deposits 12 extracellular 14 deposits 13 amyloid 14 deposits 14 deposits 18 tangles 15 , 18 tangles 16 intracellular 18 tangles 17 neurofibrillary 18 tangles 18 tangles 23 and 18 tangles 26 . 19 ( 23 and 20 nfts 23 and 22 )(, 23 and 23 and 25 death 23 and 26 . 24 neuronal 25 death hyperphosphorylation of tau is a key factor in the generation of nfts . 0 ###LEFT-WALL### 1 hyperphosphorylation 0 ###LEFT-WALL### 4 is 0 ###LEFT-WALL### 13 . 1 hyperphosphorylation 2 of 1 hyperphosphorylation 4 is 2 of 3 tau 4 is 7 factor 5 a 7 factor 6 key 7 factor 7 factor 8 in 8 in 10 generation 9 the 10 generation 10 generation 11 of 11 of 12 nfts mitogen activated protein kinase 1 ( mapk1 ) and protein kinase c beta ( prkcb ) [are] thought to play a role in hyperphosphorylation , and prckb is thought to be involved in hypoxic stress and vascular dysfunction , and to trigger mapk phosphorylation pathways . 0 ###LEFT-WALL### 1 mitogen 0 ###LEFT-WALL### 2 activated 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 40 and 0 ###LEFT-WALL### 46 . 1 mitogen 2 activated 2 activated 4 kinase 3 protein 4 kinase 4 kinase 5 1 4 kinase 7 mapk1 6 ( 7 mapk1 7 mapk1 8 ) 9 and 13 beta 9 and 29 thought 10 protein 13 beta 11 kinase 12 c 11 kinase 13 beta 13 beta 15 prkcb 13 beta 18 thought 14 ( 15 prkcb 15 prkcb 16 ) 18 thought 19 to 19 to 20 play 21 a 22 role 22 role 23 in 22 role 28 is 23 in 26 and 24 hyperphosphorylation 26 and 25 , 26 and 26 and 27 prckb 28 is 29 thought 29 thought 30 to 30 to 40 and 31 be 32 involved 31 be 40 and 32 involved 33 in 33 in 36 and 34 hypoxic 35 stress 35 stress 36 and 36 and 38 dysfunction 36 and 39 , 37 vascular 38 dysfunction 40 and 41 to 40 and 42 trigger 41 to 42 trigger 42 trigger 45 pathways 43 mapk 45 pathways 44 phosphorylation 45 pathways we performed single - cell analyses of neurons with different vulnerabilities to ad - related changes . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 performed 0 ###LEFT-WALL### 15 related 1 we 2 performed 2 performed 6 analyses 2 performed 9 with 2 performed 12 to 3 single 4 - 3 single 5 cell 5 cell 6 analyses 6 analyses 7 of 7 of 8 neurons 9 with 11 vulnerabilities 10 different 11 vulnerabilities 12 to 13 ad 14 - 15 related 15 related 16 changes 15 related 17 . using quantitative pcr ( qpcr ) , we measured the levels of mapk1 and prkcb transcript in ca1 ( high vulnerability ) , ca2 pyramidal cells from the hippocampus , granule cells from the cerebellum ( low vulnerability ) , and neurons from the brain stem ( nucleus tractus spinalis nervi trigemini , characterized by early neurophysiological deficits ) at progressive braak stages compared to age - matched controls . 0 ###LEFT-WALL### 8 we 0 ###LEFT-WALL### 41 and 0 ###LEFT-WALL### 70 . 1 using 3 pcr 1 using 7 , 1 using 8 we 2 quantitative 3 pcr 3 pcr 5 qpcr 4 ( 5 qpcr 5 qpcr 6 ) 8 we 41 and 9 measured 11 levels 9 measured 41 and 10 the 11 levels 11 levels 12 of 12 of 14 and 13 mapk1 14 and 14 and 16 transcript 14 and 17 in 14 and 21 vulnerability 14 and 26 cells 15 prkcb 16 transcript 17 in 18 ca1 19 ( 21 vulnerability 20 high 21 vulnerability 21 vulnerability 22 ) 23 , 26 cells 24 ca2 26 cells 25 pyramidal 26 cells 26 cells 27 from 26 cells 40 , 27 from 29 hippocampus 28 the 29 hippocampus 29 hippocampus 32 cells 30 , 32 cells 31 granule 32 cells 32 cells 33 from 32 cells 40 , 33 from 35 cerebellum 34 the 35 cerebellum 35 cerebellum 38 vulnerability 36 ( 38 vulnerability 37 low 38 vulnerability 38 vulnerability 39 ) 41 and 42 neurons 42 neurons 43 from 42 neurons 54 characterized 42 neurons 60 at 42 neurons 69 controls 43 from 46 stem 44 the 46 stem 45 brain 46 stem 46 stem 52 trigemini 47 ( 52 trigemini 48 nucleus 49 tractus 49 tractus 51 nervi 50 spinalis 51 nervi 51 nervi 52 trigemini 52 trigemini 53 , 53 , 54 characterized 54 characterized 55 by 54 characterized 59 ) 55 by 58 deficits 56 early 58 deficits 57 neurophysiological 58 deficits 60 at 63 stages 61 progressive 63 stages 62 braak 63 stages 63 stages 64 compared 64 compared 65 to 64 compared 67 - 64 compared 68 matched 65 to 66 age the highly vulnerable ca1 pyramidal neurons were characterized by age - and disease - unrelated increases in prckb levels and by age - and disease - related increases in mapk1 levels . 0 ###LEFT-WALL### 4 ca1 0 ###LEFT-WALL### 8 characterized 0 ###LEFT-WALL### 24 and 0 ###LEFT-WALL### 32 . 1 the 4 ca1 2 highly 3 vulnerable 3 vulnerable 4 ca1 4 ca1 6 neurons 4 ca1 7 were 4 ca1 8 characterized 5 pyramidal 6 neurons 6 neurons 7 were 8 characterized 9 by 8 characterized 16 increases 9 by 12 and 10 age 12 and 11 - 12 and 12 and 13 disease 12 and 14 - 15 unrelated 16 increases 16 increases 20 and 17 in 19 levels 17 in 20 and 18 prckb 19 levels 20 and 21 by 21 by 22 age 23 - 24 and 24 and 25 disease 24 and 31 levels 25 disease 31 levels 26 - 27 related 27 related 28 increases 27 related 29 in 27 related 31 levels 29 in 30 mapk1 in contrast , low prkcb levels were found in ca2 pyramidal neurons , and mapk1 levels were elevated in controls and intermediate ad stages . 0 ###LEFT-WALL### 5 prkcb 0 ###LEFT-WALL### 8 found 0 ###LEFT-WALL### 25 . 1 in 2 contrast 1 in 3 , 1 in 5 prkcb 4 low 5 prkcb 5 prkcb 6 levels 5 prkcb 7 were 5 prkcb 8 found 6 levels 7 were 8 found 9 in 8 found 16 levels 8 found 18 elevated 9 in 10 ca2 11 pyramidal 16 levels 12 neurons 14 and 13 , 14 and 14 and 15 mapk1 14 and 16 levels 16 levels 17 were 17 were 18 elevated 18 elevated 19 in 19 in 21 and 20 controls 21 and 21 and 24 stages 22 intermediate 24 stages 23 ad 24 stages both prkcb and mapk1 were increased in the late ad stages . 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 6 increased 0 ###LEFT-WALL### 12 . 1 both 3 and 2 prkcb 3 and 3 and 4 mapk1 3 and 5 were 5 were 6 increased 6 increased 7 in 7 in 11 stages 8 the 11 stages 9 late 11 stages 10 ad 11 stages mapk1 and prkcb levels were low in the brainstem and cerebellum . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 5 were 0 ###LEFT-WALL### 12 . 1 mapk1 2 and 2 and 4 levels 2 and 5 were 3 prkcb 4 levels 5 were 6 low 6 low 7 in 7 in 10 and 8 the 9 brainstem 9 brainstem 10 and 10 and 11 cerebellum we propose that alterations in the expression of these two genes occur early in the pathogenesis of ad in a region - specific manner . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 propose 0 ###LEFT-WALL### 22 - 0 ###LEFT-WALL### 25 . 1 we 2 propose 2 propose 3 that 3 that 4 alterations 3 that 12 occur 4 alterations 5 in 5 in 7 expression 6 the 7 expression 7 expression 8 of 8 of 11 genes 9 these 10 two 10 two 11 genes 12 occur 13 early 12 occur 14 in 12 occur 19 in 14 in 16 pathogenesis 15 the 16 pathogenesis 16 pathogenesis 17 of 17 of 18 ad 19 in 21 region 20 a 21 region 22 - 24 manner 23 specific 24 manner in addition , multiple signal transduction pathways need to be affected to result in ad instead of physiological aging . 0 ###LEFT-WALL### 7 pathways 0 ###LEFT-WALL### 8 need 0 ###LEFT-WALL### 20 . 1 in 2 addition 1 in 3 , 1 in 7 pathways 4 multiple 7 pathways 5 signal 7 pathways 6 transduction 7 pathways 7 pathways 8 need 8 need 9 to 8 need 13 result 9 to 10 be 10 be 11 affected 11 affected 12 to 12 to 13 result 13 result 14 in 13 result 17 of 14 in 15 ad 16 instead 17 of 17 of 19 aging 18 physiological 19 aging age - related alterations in human gut microbiota composition have been thoroughly described , but a detailed functional description of the intestinal bacterial coding capacity is still missing . 0 ###LEFT-WALL### 4 alterations 0 ###LEFT-WALL### 13 described 0 ###LEFT-WALL### 15 but 0 ###LEFT-WALL### 29 . 1 age 2 - 1 age 4 alterations 3 related 4 alterations 4 alterations 5 in 4 alterations 10 have 5 in 9 composition 6 human 9 composition 7 gut 8 microbiota 8 microbiota 9 composition 10 have 11 been 11 been 12 thoroughly 11 been 13 described 14 , 15 but 15 but 19 description 15 but 26 is 16 a 17 detailed 16 a 19 description 17 detailed 19 description 18 functional 19 description 19 description 20 of 19 description 26 is 20 of 25 capacity 21 the 25 capacity 22 intestinal 25 capacity 23 bacterial 25 capacity 24 coding 25 capacity 26 is 28 missing 27 still 28 missing in order to elucidate the contribution of the gut metagenome to the complex mosaic of human longevity , we applied shotgun sequencing to total fecal bacterial dna in a selection of samples belonging to a well - characterized human ageing cohort . 0 ###LEFT-WALL### 19 we 0 ###LEFT-WALL### 20 applied 0 ###LEFT-WALL### 37 - 0 ###LEFT-WALL### 42 . 1 in 2 order 1 in 18 , 1 in 19 we 2 order 3 to 2 order 4 elucidate 3 to 4 elucidate 4 elucidate 6 contribution 4 elucidate 11 to 5 the 6 contribution 6 contribution 7 of 7 of 10 metagenome 8 the 10 metagenome 9 gut 10 metagenome 11 to 14 mosaic 12 the 14 mosaic 13 complex 14 mosaic 14 mosaic 15 of 15 of 17 longevity 16 human 17 longevity 19 we 20 applied 20 applied 22 sequencing 20 applied 23 to 20 applied 28 in 21 shotgun 22 sequencing 23 to 27 dna 24 total 27 dna 25 fecal 27 dna 26 bacterial 27 dna 28 in 30 selection 29 a 30 selection 30 selection 31 of 30 selection 33 belonging 30 selection 34 to 31 of 32 samples 34 to 36 well 35 a 36 well 37 - 41 cohort 38 characterized 40 ageing 39 human 40 ageing 40 ageing 41 cohort the age [-] related trajectory of the human gut microbiome was characterized by loss of genes for shortchain fatty acid production and an overall decrease in the saccharolytic potential , while proteolytic functions were more abundant than in the intestinal metagenome of younger adults . 0 ###LEFT-WALL### 5 trajectory 0 ###LEFT-WALL### 12 characterized 1 the 5 trajectory 2 age 4 related 4 related 5 trajectory 5 trajectory 6 of 5 trajectory 11 was 6 of 10 microbiome 7 the 10 microbiome 8 human 9 gut 9 gut 10 microbiome 11 was 12 characterized 12 characterized 13 by 12 characterized 17 for 12 characterized 26 in 12 characterized 31 while 13 by 14 loss 14 loss 15 of 15 of 16 genes 17 for 18 shortchain 18 shortchain 22 and 18 shortchain 25 decrease 19 fatty 20 acid 20 acid 21 production 21 production 22 and 22 and 24 overall 22 and 25 decrease 23 an 24 overall 26 in 29 potential 27 the 29 potential 28 saccharolytic 29 potential 30 , 31 while 31 while 33 functions 31 while 34 were 31 while 45 . 32 proteolytic 33 functions 33 functions 34 were 34 were 35 more 34 were 36 abundant 36 abundant 37 than 36 abundant 38 in 38 in 41 metagenome 39 the 41 metagenome 40 intestinal 41 metagenome 41 metagenome 42 of 42 of 44 adults 43 younger 44 adults this altered functional profile was associated with [a] relevant enrichment in " pathobionts " , i.e . opportunistic pro - inflammatory bacteria [generally] present in the adult gut ecosystem in low numbers . 0 ###LEFT-WALL### 4 profile 0 ###LEFT-WALL### 6 associated 0 ###LEFT-WALL### 17 . 0 ###LEFT-WALL### 33 . 1 this 2 altered 2 altered 4 profile 3 functional 4 profile 4 profile 5 was 5 was 6 associated 6 associated 7 with 6 associated 11 in 6 associated 15 , 6 associated 16 i.e 7 with 10 enrichment 9 relevant 10 enrichment 11 in 12 " 11 in 13 pathobionts 13 pathobionts 14 " 17 . 19 pro 17 . 20 - 18 opportunistic 19 pro 20 - 22 bacteria 21 inflammatory 22 bacteria 22 bacteria 24 present 24 present 25 in 24 present 30 in 25 in 29 ecosystem 26 the 29 ecosystem 27 adult 29 ecosystem 28 gut 29 ecosystem 30 in 32 numbers 31 low 32 numbers finally , as a signature for long life we identified 116 microbial genes that significantly correlated with ageing . 0 ###LEFT-WALL### 9 we 0 ###LEFT-WALL### 10 identified 0 ###LEFT-WALL### 19 . 1 finally 2 , 1 finally 9 we 3 as 5 signature 3 as 9 we 4 a 5 signature 5 signature 6 for 6 for 8 life 7 long 8 life 9 we 10 identified 10 identified 13 genes 11 116 13 genes 12 microbial 13 genes 13 genes 16 correlated 14 that 15 significantly 15 significantly 16 correlated 16 correlated 17 with 17 with 18 ageing collectively , our data emphasize the relationship between intestinal bacteria and human metabolism , by detailing the modifications in the gut microbiota as a consequence [of] [and/or] promoter of the physiological changes occurring in the human host upon ageing . 0 ###LEFT-WALL### 4 data 0 ###LEFT-WALL### 5 emphasize 1 collectively 2 , 1 collectively 4 data 3 our 4 data 4 data 5 emphasize 5 emphasize 11 and 6 the 7 relationship 7 relationship 8 between 7 relationship 11 and 8 between 10 bacteria 9 intestinal 10 bacteria 11 and 13 metabolism 11 and 15 by 12 human 13 metabolism 14 , 15 by 15 by 16 detailing 15 by 40 . 16 detailing 18 modifications 17 the 18 modifications 18 modifications 19 in 18 modifications 22 microbiota 18 modifications 29 of 19 in 21 gut 20 the 21 gut 22 microbiota 23 as 23 as 28 promoter 24 a 28 promoter 25 consequence 28 promoter 29 of 32 changes 30 the 32 changes 31 physiological 32 changes 32 changes 33 occurring 33 occurring 34 in 33 occurring 38 upon 34 in 37 host 35 the 37 host 36 human 37 host 38 upon 39 ageing patients with some progeroid syndromes , such as werner [syndrome] , exhibit atherosclerotic cardiovascular disease ( cvd ) at a young age as a manifestation of premature aging . 0 ###LEFT-WALL### 1 patients 0 ###LEFT-WALL### 12 exhibit 0 ###LEFT-WALL### 29 . 1 patients 2 with 1 patients 12 exhibit 2 with 5 syndromes 3 some 5 syndromes 4 progeroid 5 syndromes 5 syndromes 8 as 6 , 8 as 7 such 8 as 8 as 9 werner 8 as 11 , 12 exhibit 15 disease 12 exhibit 19 at 12 exhibit 23 as 13 atherosclerotic 15 disease 14 cardiovascular 15 disease 15 disease 17 cvd 16 ( 17 cvd 17 cvd 18 ) 19 at 22 age 20 a 21 young 20 a 22 age 21 young 22 age 23 as 25 manifestation 24 a 25 manifestation 25 manifestation 26 of 26 of 28 aging 27 premature 28 aging recent studies have revealed that most progeroid syndromes are caused by genetic defects in specific molecules involved in the dna damage response , a cornerstone of genome stability . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 4 revealed 1 recent 2 studies 2 studies 3 have 3 have 4 revealed 4 revealed 5 that 5 that 8 syndromes 5 that 10 caused 6 most 8 syndromes 7 progeroid 8 syndromes 8 syndromes 9 are 9 are 10 caused 10 caused 11 by 10 caused 14 in 11 by 13 defects 12 genetic 13 defects 14 in 16 molecules 15 specific 16 molecules 16 molecules 17 involved 17 involved 18 in 18 in 22 response 19 the 22 response 20 dna 22 response 21 damage 22 response 22 response 25 cornerstone 23 , 25 cornerstone 24 a 25 cornerstone 25 cornerstone 26 of 25 cornerstone 29 . 26 of 28 stability 27 genome 28 stability ionizing radiation is one of the most potent genotoxic stimuli and causes various kinds of dna damage . 0 ###LEFT-WALL### 1 ionizing 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 18 . 1 ionizing 2 radiation 1 ionizing 11 and 3 is 4 one 3 is 11 and 4 one 5 of 5 of 10 stimuli 6 the 7 most 7 most 10 stimuli 8 potent 10 stimuli 9 genotoxic 10 stimuli 11 and 12 causes 11 and 17 damage 13 various 14 kinds 14 kinds 15 of 14 kinds 17 damage 15 of 17 damage 16 dna 17 damage further , there is increasing evidence that therapeutic radiation treatments can cause cardiovascular complications . 0 ###LEFT-WALL### 3 there 0 ###LEFT-WALL### 4 is 0 ###LEFT-WALL### 15 . 1 further 2 , 1 further 3 there 3 there 4 is 4 is 6 evidence 5 increasing 6 evidence 6 evidence 7 that 7 that 10 treatments 7 that 12 cause 8 therapeutic 9 radiation 9 radiation 10 treatments 10 treatments 11 can 11 can 12 cause 12 cause 14 complications 13 cardiovascular 14 complications here , we describe the dna damage and subsequent response , review recent advances in the understanding of the molecular basis of progeroid syndromes ( especially those syndromes that involve cvd ) , review the pathological and epidemiological analysis of radiation - induced cvd , and discuss the possible role of dna damage and the dna damage response in the pathogenesis of atherosclerotic cvd . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 describe 0 ###LEFT-WALL### 11 , 0 ###LEFT-WALL### 65 . 1 here 2 , 1 here 3 we 3 we 4 describe 4 describe 8 and 5 the 8 and 6 dna 7 damage 7 damage 8 and 8 and 10 response 9 subsequent 10 response 11 , 33 , 12 review 14 advances 12 review 15 in 12 review 33 , 13 recent 14 advances 15 in 17 understanding 16 the 17 understanding 17 understanding 18 of 17 understanding 28 syndromes 18 of 21 basis 19 the 21 basis 20 molecular 21 basis 21 basis 22 of 22 of 24 syndromes 23 progeroid 24 syndromes 25 ( 26 especially 25 ( 28 syndromes 27 those 28 syndromes 28 syndromes 29 that 28 syndromes 30 involve 28 syndromes 32 ) 29 that 30 involve 30 involve 31 cvd 33 , 46 and 34 review 39 analysis 34 review 46 and 35 the 39 analysis 36 pathological 37 and 37 and 38 epidemiological 37 and 39 analysis 39 analysis 40 of 40 of 41 radiation 41 radiation 44 cvd 42 - 44 cvd 43 induced 44 cvd 44 cvd 45 , 46 and 47 discuss 47 discuss 54 and 47 discuss 59 in 48 the 50 role 49 possible 50 role 50 role 51 of 50 role 54 and 51 of 53 damage 52 dna 53 damage 54 and 58 response 55 the 58 response 56 dna 58 response 57 damage 58 response 59 in 61 pathogenesis 60 the 61 pathogenesis 61 pathogenesis 62 of 62 of 64 cvd 63 atherosclerotic 64 cvd eukaryotic cells respond to various forms of stress by blocking mrna translation initiation via the phosphorylation of the alpha ( α ) subunit of eif2 at serine 51 ( s51 ) ( eifαp ) . 0 ###LEFT-WALL### 2 cells 0 ###LEFT-WALL### 3 respond 0 ###LEFT-WALL### 35 . 1 eukaryotic 2 cells 2 cells 3 respond 3 respond 4 to 3 respond 9 by 4 to 6 forms 5 various 6 forms 6 forms 7 of 7 of 8 stress 9 by 10 blocking 10 blocking 13 initiation 10 blocking 14 via 11 mrna 13 initiation 12 translation 13 initiation 14 via 16 phosphorylation 15 the 16 phosphorylation 16 phosphorylation 17 of 16 phosphorylation 23 subunit 17 of 19 alpha 18 the 19 alpha 20 ( 23 subunit 21 α 22 ) 21 α 23 subunit 23 subunit 24 of 23 subunit 26 at 23 subunit 34 ) 24 of 25 eif2 26 at 27 serine 27 serine 28 51 27 serine 30 s51 27 serine 33 eifαp 29 ( 30 s51 30 s51 31 ) 32 ( 33 eifαp 33 eifαp 34 ) an important role of eif2αp is the regulation of redox homeostasis and adaptation of cells to oxidative stress . 0 ###LEFT-WALL### 3 role 0 ###LEFT-WALL### 6 is 0 ###LEFT-WALL### 19 . 1 an 2 important 1 an 3 role 2 important 3 role 3 role 4 of 3 role 6 is 4 of 5 eif2αp 6 is 8 regulation 7 the 8 regulation 8 regulation 9 of 8 regulation 14 of 9 of 12 and 10 redox 11 homeostasis 11 homeostasis 12 and 12 and 13 adaptation 14 of 15 cells 15 cells 16 to 16 to 18 stress 17 oxidative 18 stress herein , we demonstrate that eif2αp guards cells from intracellular reactive oxygen species ( ros ) via the inhibition of senescence . 0 ###LEFT-WALL### 1 herein 0 ###LEFT-WALL### 2 , 0 ###LEFT-WALL### 22 . 2 , 3 we 2 , 4 demonstrate 3 we 4 demonstrate 4 demonstrate 5 that 5 that 6 eif2αp 5 that 7 guards 6 eif2αp 7 guards 7 guards 8 cells 7 guards 17 via 8 cells 9 from 9 from 13 species 10 intracellular 12 oxygen 11 reactive 12 oxygen 12 oxygen 13 species 13 species 15 ros 14 ( 15 ros 15 ros 16 ) 17 via 19 inhibition 18 the 19 inhibition 19 inhibition 20 of 20 of 21 senescence specifically , genetic inactivation of either eif2αp or eif2α kinase perk [in] primary mouse or human fibroblasts leads to proliferative defects associated with increased dna damage , g2/m accumulation and induction of premature senescence . 0 ###LEFT-WALL### 15 or 0 ###LEFT-WALL### 17 fibroblasts 0 ###LEFT-WALL### 35 . 1 specifically 2 , 1 specifically 15 or 3 genetic 4 inactivation 4 inactivation 5 of 4 inactivation 8 or 5 of 7 eif2αp 6 either 7 eif2αp 8 or 14 mouse 8 or 15 or 9 eif2α 10 kinase 10 kinase 13 primary 11 perk 13 primary 13 primary 14 mouse 15 or 16 human 15 or 17 fibroblasts 17 fibroblasts 18 leads 17 fibroblasts 19 to 17 fibroblasts 23 with 19 to 21 defects 20 proliferative 21 defects 21 defects 22 associated 23 with 30 and 24 increased 26 damage 25 dna 26 damage 26 damage 27 , 27 , 29 accumulation 27 , 30 and 28 g2/m 29 accumulation 30 and 31 induction 30 and 32 of 32 of 34 senescence 33 premature 34 senescence impaired proliferation [of] [either] perk or eif2αp - deficient primary cells is caused by increased ros and restored by anti - oxidant treatment . 0 ###LEFT-WALL### 6 or 0 ###LEFT-WALL### 13 caused 0 ###LEFT-WALL### 24 . 1 impaired 2 proliferation 2 proliferation 5 perk 5 perk 6 or 6 or 11 cells 6 or 12 is 7 eif2αp 8 - 7 eif2αp 11 cells 9 deficient 11 cells 10 primary 11 cells 12 is 13 caused 13 caused 14 by 13 caused 19 by 14 by 17 and 15 increased 16 ros 15 increased 17 and 17 and 18 restored 19 by 23 treatment 20 anti 21 - 20 anti 23 treatment 22 oxidant 23 treatment contrary to primary cells , impaired eif2αp in immortalized mouse fibroblasts or human tumor cells provides tolerance to elevated intracellular ros levels . 0 ###LEFT-WALL### 1 contrary 0 ###LEFT-WALL### 16 provides 0 ###LEFT-WALL### 23 . 1 contrary 2 to 1 contrary 16 provides 2 to 12 or 3 primary 4 cells 4 cells 5 , 5 , 7 eif2αp 5 , 12 or 6 impaired 7 eif2αp 7 eif2αp 8 in 8 in 11 fibroblasts 9 immortalized 10 mouse 10 mouse 11 fibroblasts 12 or 15 cells 13 human 15 cells 14 tumor 15 cells 16 provides 17 tolerance 16 provides 18 to 18 to 22 levels 19 elevated 22 levels 20 intracellular 22 levels 21 ros 22 levels however , eif2αp - deficient human tumor cells are highly susceptible to extrinsic ros generated by the pro - oxidant drug doxorubicin by undergoing premature senescence . 0 ###LEFT-WALL### 8 cells 0 ###LEFT-WALL### 9 are 0 ###LEFT-WALL### 19 - 0 ###LEFT-WALL### 20 oxidant 0 ###LEFT-WALL### 27 . 1 however 2 , 1 however 8 cells 3 eif2αp 4 - 3 eif2αp 6 human 5 deficient 6 human 6 human 8 cells 7 tumor 8 cells 8 cells 9 are 9 are 11 susceptible 10 highly 11 susceptible 11 susceptible 12 to 11 susceptible 16 by 12 to 14 ros 13 extrinsic 14 ros 14 ros 15 generated 16 by 18 pro 17 the 18 pro 19 - 20 oxidant 20 oxidant 22 doxorubicin 20 oxidant 23 by 21 drug 22 doxorubicin 23 by 24 undergoing 24 undergoing 26 senescence 25 premature 26 senescence our work demonstrates that eif2αp determines cell destiny through its capacity to control senescence in response to oxidative stress . 0 ###LEFT-WALL### 2 work 0 ###LEFT-WALL### 3 demonstrates 0 ###LEFT-WALL### 20 . 1 our 2 work 2 work 3 demonstrates 3 demonstrates 4 that 4 that 5 eif2αp 4 that 6 determines 5 eif2αp 6 determines 6 determines 8 destiny 6 determines 9 through 7 cell 8 destiny 9 through 11 capacity 10 its 11 capacity 11 capacity 12 to 11 capacity 13 control 12 to 13 control 13 control 14 senescence 13 control 16 response 13 control 17 to 15 in 16 response 17 to 19 stress 18 oxidative 19 stress also , inhibition of eif2αp may be a suitable means to increase the anti - tumor effects of pro [-] oxidant drugs through the induction of senescence . 0 ###LEFT-WALL### 3 inhibition 0 ###LEFT-WALL### 7 be 0 ###LEFT-WALL### 28 . 1 also 2 , 1 also 3 inhibition 3 inhibition 4 of 3 inhibition 6 may 4 of 5 eif2αp 6 may 7 be 7 be 10 means 7 be 11 to 7 be 23 through 8 a 10 means 9 suitable 10 means 11 to 12 increase 12 increase 17 effects 13 the 17 effects 14 anti 15 - 14 anti 16 tumor 16 tumor 17 effects 17 effects 18 of 18 of 22 drugs 19 pro 21 oxidant 21 oxidant 22 drugs 23 through 25 induction 24 the 25 induction 25 induction 26 of 26 of 27 senescence purpose : we examined the association of corneal hysteresis ( ch ) with heidelberg retina tomograph ( hrt ) - and glaucoma detection with variable corneal compensation scanning laser polarimeter ( gdxvcc ) - derived measures in a british population . 0 ###LEFT-WALL### 1 purpose 0 ###LEFT-WALL### 2 : 2 : 3 we 2 : 4 examined 2 : 41 . 3 we 4 examined 4 examined 21 and 4 examined 29 laser 5 the 6 association 6 association 7 of 6 association 13 with 6 association 21 and 7 of 9 hysteresis 8 corneal 9 hysteresis 9 hysteresis 11 ch 10 ( 11 ch 11 ch 12 ) 13 with 16 tomograph 14 heidelberg 15 retina 15 retina 16 tomograph 16 tomograph 18 hrt 17 ( 18 hrt 18 hrt 19 ) 20 - 21 and 21 and 23 detection 21 and 24 with 21 and 28 scanning 21 and 29 laser 22 glaucoma 23 detection 24 with 27 compensation 25 variable 26 corneal 26 corneal 27 compensation 29 laser 36 measures 29 laser 37 in 30 polarimeter 32 gdxvcc 30 polarimeter 34 - 30 polarimeter 36 measures 31 ( 32 gdxvcc 32 gdxvcc 33 ) 35 derived 36 measures 37 in 40 population 38 a 39 british 38 a 40 population 39 british 40 population methods : the epic - norfolk eye study is nested within a multicenter cohort study -- the european prospective investigation of cancer . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 5 - 0 ###LEFT-WALL### 23 . 1 methods 2 : 2 : 4 epic 3 the 4 epic 5 - 7 eye 5 - 10 nested 5 - 16 -- 6 norfolk 7 eye 7 eye 8 study 7 eye 9 is 7 eye 10 nested 8 study 9 is 10 nested 11 within 11 within 15 study 12 a 13 multicenter 12 a 15 study 13 multicenter 14 cohort 14 cohort 15 study 16 -- 20 investigation 17 the 18 european 18 european 20 investigation 19 prospective 20 investigation 20 investigation 21 of 21 of 22 cancer ocular response analyzer ( ora ) , hrt3 , and gdxvcc measurements were taken at the research clinic . 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 14 taken 0 ###LEFT-WALL### 19 . 1 ocular 2 response 2 response 8 hrt3 3 analyzer 5 ora 3 analyzer 7 , 3 analyzer 8 hrt3 4 ( 5 ora 5 ora 6 ) 8 hrt3 10 and 9 , 10 and 10 and 12 measurements 10 and 13 were 11 gdxvcc 12 measurements 13 were 14 taken 14 taken 15 at 15 at 18 clinic 16 the 18 clinic 17 research 18 clinic three ora measurements [were] taken per eye , and the single best value used . 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 12 best 0 ###LEFT-WALL### 15 . 1 three 3 measurements 2 ora 3 measurements 3 measurements 5 taken 3 measurements 6 per 3 measurements 9 and 6 per 7 eye 8 , 9 and 9 and 11 single 9 and 12 best 10 the 11 single 12 best 13 value 13 value 14 used participants meeting predefined criteria [were] referred for a second examination , including goldmann applanation tonometry ( gat ) and central corneal thickness ( cct ) measurement . 0 ###LEFT-WALL### 26 measurement 0 ###LEFT-WALL### 27 . 1 participants 3 predefined 2 meeting 3 predefined 3 predefined 4 criteria 4 criteria 6 referred 4 criteria 19 and 6 referred 7 for 6 referred 12 including 7 for 10 examination 8 a 9 second 9 second 10 examination 11 , 12 including 12 including 15 tonometry 12 including 18 ) 13 goldmann 14 applanation 14 applanation 15 tonometry 15 tonometry 17 gat 16 ( 17 gat 17 gat 18 ) 19 and 22 thickness 19 and 24 cct 19 and 26 measurement 20 central 22 thickness 21 corneal 22 thickness 23 ( 24 cct 24 cct 25 ) generalized estimating equation models were used to examine the associations of ch with hrt and gdxvcc parameters , adjusted for disc area . 0 ###LEFT-WALL### 18 , 0 ###LEFT-WALL### 23 . 1 generalized 3 equation 1 generalized 13 with 1 generalized 18 , 2 estimating 3 equation 3 equation 4 models 3 equation 8 examine 4 models 5 were 5 were 6 used 6 used 7 to 6 used 8 examine 7 to 8 examine 8 examine 10 associations 9 the 10 associations 10 associations 11 of 11 of 12 ch 13 with 16 gdxvcc 13 with 17 parameters 14 hrt 15 and 15 and 16 gdxvcc 18 , 19 adjusted 19 adjusted 20 for 20 for 22 area 21 disc 22 area the gdxvcc analyses were adjusted further for typical [scan] score [to] handle atypical retardation . 0 ###LEFT-WALL### 3 analyses 0 ###LEFT-WALL### 5 adjusted 0 ###LEFT-WALL### 15 . 1 the 3 analyses 2 gdxvcc 3 analyses 3 analyses 4 were 4 were 5 adjusted 5 adjusted 6 further 5 adjusted 7 for 7 for 14 retardation 8 typical 10 score 10 score 14 retardation 12 handle 14 retardation 13 atypical 14 retardation results : there were complete research clinic data from 5134 participants . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 4 were 0 ###LEFT-WALL### 12 . 2 : 3 there 2 : 4 were 3 there 4 were 4 were 8 data 5 complete 6 research 6 research 8 data 7 clinic 8 data 8 data 9 from 9 from 11 participants 10 5134 11 participants in the 602 participants undergoing the second examination , ch was associated negatively with lcdr ( p = 0.008 ) after adjustment for gat , cct , and other possible confounders . 0 ###LEFT-WALL### 10 ch 0 ###LEFT-WALL### 12 associated 0 ###LEFT-WALL### 32 . 1 in 4 participants 1 in 9 , 1 in 10 ch 2 the 4 participants 3 602 4 participants 4 participants 5 undergoing 5 undergoing 8 examination 6 the 7 second 6 the 8 examination 10 ch 11 was 11 was 12 associated 12 associated 13 negatively 12 associated 14 with 14 with 28 and 15 lcdr 18 = 15 lcdr 21 after 15 lcdr 25 , 16 ( 18 = 17 p 18 = 18 = 19 0.008 18 = 20 ) 21 after 22 adjustment 22 adjustment 23 for 23 for 24 gat 25 , 26 cct 25 , 28 and 27 , 28 and 28 and 31 confounders 29 other 31 confounders 30 possible 31 confounders conclusions : lower ch was associated with hrt and gdxvcc parameters in a direction that is seen in glaucoma and with ageing . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 23 . 2 : 4 ch 2 : 6 associated 3 lower 4 ch 4 ch 5 was 5 was 6 associated 6 associated 7 with 7 with 9 and 7 with 12 in 8 hrt 9 and 9 and 11 parameters 10 gdxvcc 11 parameters 12 in 14 direction 13 a 14 direction 14 direction 17 seen 14 direction 20 and 15 that 16 is 16 is 17 seen 18 in 19 glaucoma 18 in 20 and 20 and 21 with 21 with 22 ageing further research is required to establish if this is a causal relationship , or due to residual confounding by age , iop , or cct . 0 ###LEFT-WALL### 2 research 0 ###LEFT-WALL### 4 required 0 ###LEFT-WALL### 26 . 1 further 2 research 2 research 3 is 3 is 4 required 4 required 5 to 4 required 16 to 4 required 19 by 5 to 6 establish 6 establish 7 if 7 if 8 this 7 if 9 is 8 this 9 is 9 is 14 or 10 a 11 causal 10 a 12 relationship 11 causal 12 relationship 12 relationship 14 or 13 , 14 or 14 or 15 due 16 to 18 confounding 17 residual 18 confounding 19 by 24 or 20 age 21 , 21 , 22 iop 21 , 24 or 23 , 24 or 24 or 25 cct background : the family , together with the individual and society , and the state and market are the three pillars of well - being and social security over the life course , with responsibility for the health of older adults . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 42 . 1 background 2 : 2 : 4 family 3 the 4 family 4 family 7 with 5 , 7 with 6 together 7 with 7 with 10 and 7 with 12 , 8 the 9 individual 9 individual 10 and 10 and 11 society 13 and 16 and 13 and 18 are 14 the 15 state 15 state 16 and 16 and 17 market 16 and 18 are 18 are 21 pillars 19 the 20 three 20 three 21 pillars 21 pillars 22 of 21 pillars 34 with 21 pillars 36 for 22 of 23 well 23 well 26 and 24 - 26 and 25 being 26 and 26 and 28 security 26 and 29 over 26 and 33 , 27 social 28 security 29 over 32 course 30 the 32 course 31 life 32 course 34 with 35 responsibility 36 for 38 health 37 the 38 health 38 health 39 of 39 of 41 adults 40 older 41 adults objective : the aim of current study was to explore the effect of intergenerational and intragenerational support on perceived health of older adults . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 24 . 2 : 4 aim 2 : 8 was 3 the 4 aim 4 aim 5 of 4 aim 8 was 5 of 7 study 6 current 7 study 8 was 9 to 9 to 10 explore 10 explore 12 effect 10 explore 18 on 11 the 12 effect 12 effect 13 of 13 of 17 support 14 intergenerational 15 and 15 and 16 intragenerational 15 and 17 support 18 on 20 health 19 perceived 20 health 20 health 21 of 21 of 23 adults 22 older 23 adults methods : a cross - sectional [survey] with 64.36 % ( 1318/2048 ) response rate [was] conducted [door] to door [in] rural china with a sample of 1318 individuals aged 60 years and older . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 1 methods 2 : 2 : 4 cross 3 a 4 cross 4 cross 6 sectional 5 - 6 sectional 6 sectional 8 with 6 sectional 19 to 6 sectional 33 and 6 sectional 35 . 8 with 10 % 8 with 17 conducted 9 64.36 10 % 10 % 12 1318/2048 11 ( 12 1318/2048 12 1318/2048 13 ) 14 response 15 rate 15 rate 17 conducted 19 to 23 china 20 door 23 china 22 rural 23 china 23 china 24 with 23 china 27 of 23 china 30 aged 24 with 26 sample 25 a 26 sample 27 of 29 individuals 28 1318 29 individuals 31 60 32 years 32 years 33 and 33 and 34 older there were three sets of independent variables : intergenerational support from children as well as intragenerational spousal support and intragenerational sibling support , sociodemographic variables , and behaviour variables . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 were 0 ###LEFT-WALL### 8 : 0 ###LEFT-WALL### 30 . 1 there 2 were 2 were 4 sets 3 three 4 sets 4 sets 5 of 5 of 7 variables 6 independent 7 variables 8 : 27 and 9 intergenerational 10 support 10 support 11 from 10 support 23 , 11 from 19 and 12 children 15 as 12 children 19 and 13 as 14 well 14 well 15 as 15 as 18 support 16 intragenerational 18 support 17 spousal 18 support 19 and 22 support 20 intragenerational 21 sibling 21 sibling 22 support 23 , 25 variables 23 , 27 and 24 sociodemographic 25 variables 26 , 27 and 27 and 29 variables 28 behaviour 29 variables multiple logistic regression analysis was used to analyse the influence of family member support on physical and psychological health . 0 ###LEFT-WALL### 4 analysis 0 ###LEFT-WALL### 6 used 0 ###LEFT-WALL### 20 . 1 multiple 4 analysis 2 logistic 3 regression 3 regression 4 analysis 4 analysis 5 was 5 was 6 used 6 used 7 to 6 used 8 analyse 7 to 8 analyse 8 analyse 10 influence 8 analyse 15 on 9 the 10 influence 10 influence 11 of 11 of 14 support 12 family 14 support 13 member 14 support 15 on 19 health 16 physical 17 and 17 and 18 psychological 17 and 19 health however , intragenerational support from spouse [and] siblings was not significant . 0 ###LEFT-WALL### 4 support 0 ###LEFT-WALL### 9 was 0 ###LEFT-WALL### 12 . 1 however 2 , 1 however 4 support 3 intragenerational 4 support 4 support 5 from 4 support 9 was 5 from 8 siblings 6 spouse 8 siblings 9 was 10 not 9 was 11 significant 10 not 11 significant conclusion : the importance of intergenerational support from children would suggest that family practice and health - related policy of older adults may need to be extended to their children . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 4 importance 2 : 11 suggest 2 : 31 . 3 the 4 importance 4 importance 5 of 4 importance 10 would 5 of 7 support 6 intergenerational 7 support 7 support 8 from 8 from 9 children 10 would 11 suggest 11 suggest 12 that 12 that 13 family 12 that 15 and 14 practice 15 and 15 and 24 need 16 health 23 may 17 - 18 related 18 related 19 policy 18 related 23 may 19 policy 20 of 20 of 22 adults 21 older 22 adults 23 may 24 need 24 need 25 to 24 need 27 extended 25 to 26 be 26 be 27 extended 27 extended 28 to 28 to 30 children 29 their 30 children with the rapid development of global population movements , family practices need to pay attention to the changes of family support among migrant families . 0 ###LEFT-WALL### 11 practices 0 ###LEFT-WALL### 12 need 0 ###LEFT-WALL### 25 . 1 with 4 development 1 with 9 , 1 with 11 practices 2 the 4 development 3 rapid 4 development 4 development 5 of 5 of 8 movements 6 global 7 population 7 population 8 movements 10 family 11 practices 11 practices 12 need 12 need 13 to 12 need 14 pay 13 to 14 pay 14 pay 15 attention 14 pay 21 support 15 attention 16 to 16 to 18 changes 17 the 18 changes 18 changes 19 of 19 of 20 family 21 support 22 among 22 among 24 families 23 migrant 24 families this project assessed dynamic balance and stability in aged lawn bowlers during the delivery stride . 0 ###LEFT-WALL### 2 project 0 ###LEFT-WALL### 3 assessed 0 ###LEFT-WALL### 16 . 1 this 2 project 2 project 3 assessed 3 assessed 6 and 3 assessed 8 in 3 assessed 12 during 4 dynamic 5 balance 5 balance 6 and 6 and 7 stability 8 in 11 bowlers 9 aged 10 lawn 10 lawn 11 bowlers 12 during 15 stride 13 the 15 stride 14 delivery 15 stride participants were divided into two groups : aged 65 years or less ( n = 14 ) and aged over 65 years ( n = 16 ) . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 3 divided 0 ###LEFT-WALL### 7 : 1 participants 2 were 2 were 3 divided 3 divided 4 into 4 into 6 groups 5 two 6 groups 7 : 18 and 7 : 28 . 8 aged 11 or 8 aged 18 and 9 65 10 years 10 years 11 or 11 or 12 less 11 or 15 = 13 ( 15 = 14 n 15 = 15 = 16 14 15 = 17 ) 18 and 19 aged 19 aged 22 years 20 over 21 65 21 65 22 years 22 years 25 = 23 ( 25 = 24 n 25 = 25 = 26 16 25 = 27 ) standard balance - based center [of] pressure ( cop ) and ground reaction force variables were recorded and a dynamic postural stability index ( dpsi ) was used for calculating during ten deliveries . 0 ###LEFT-WALL### 2 balance 0 ###LEFT-WALL### 3 - 1 standard 2 balance 3 - 11 and 3 - 18 and 3 - 34 . 4 based 7 pressure 4 based 11 and 5 center 7 pressure 7 pressure 9 cop 8 ( 9 cop 9 cop 10 ) 11 and 12 ground 12 ground 13 reaction 13 reaction 14 force 13 reaction 17 recorded 14 force 15 variables 14 force 16 were 14 force 17 recorded 15 variables 16 were 18 and 25 dpsi 18 and 28 used 19 a 25 dpsi 20 dynamic 21 postural 21 postural 22 stability 22 stability 23 index 23 index 25 dpsi 24 ( 25 dpsi 25 dpsi 26 ) 25 dpsi 27 was 27 was 28 used 28 used 29 for 29 for 30 calculating 30 calculating 31 during 30 calculating 33 deliveries 31 during 32 ten none of the balance variables correlated significantly with age although years of bowling experience correlated with dpsi scores ( r = - [.] 42 , p = [.] 019 ) . 0 ###LEFT-WALL### 1 none 0 ###LEFT-WALL### 18 scores 0 ###LEFT-WALL### 31 . 1 none 2 of 1 none 6 correlated 1 none 18 scores 2 of 5 variables 3 the 5 variables 4 balance 5 variables 6 correlated 7 significantly 6 correlated 8 with 6 correlated 10 although 8 with 9 age 10 although 11 years 10 although 15 correlated 11 years 12 of 11 years 15 correlated 12 of 13 bowling 13 bowling 14 experience 15 correlated 16 with 16 with 17 dpsi 18 scores 21 = 18 scores 27 = 19 ( 21 = 20 r 21 = 21 = 22 - 22 - 24 42 22 - 27 = 25 , 27 = 26 p 27 = 27 = 29 019 27 = 30 ) the [over] 65 group had significantly greater variance in the mediolateral cop movements , with no other significant differences in balance or postural stability variables between groups . 0 ###LEFT-WALL### 4 group 0 ###LEFT-WALL### 5 had 1 the 4 group 3 65 4 group 4 group 5 had 5 had 8 variance 5 had 9 in 5 had 15 with 6 significantly 7 greater 7 greater 8 variance 9 in 13 movements 10 the 13 movements 11 mediolateral 13 movements 12 cop 13 movements 14 , 15 with 15 with 22 or 15 with 28 . 16 no 17 other 17 other 19 differences 18 significant 19 differences 19 differences 20 in 19 differences 22 or 20 in 21 balance 22 or 25 variables 22 or 26 between 23 postural 24 stability 24 stability 25 variables 26 between 27 groups analysis of covariance indicated that the dpsi data [were] influenced significantly by bowling experience regardless of age group . 0 ###LEFT-WALL### 1 analysis 0 ###LEFT-WALL### 4 indicated 0 ###LEFT-WALL### 19 . 1 analysis 2 of 1 analysis 4 indicated 2 of 3 covariance 4 indicated 5 that 5 that 8 data 5 that 18 group 6 the 8 data 7 dpsi 8 data 8 data 10 influenced 8 data 18 group 10 influenced 11 significantly 10 influenced 12 by 10 influenced 16 of 12 by 13 bowling 13 bowling 14 experience 15 regardless 16 of 16 of 17 age it was concluded that in older aged lawn bowlers , playing experience rather than age is a key determinant of balance control during the lawn bowls delivery action . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 3 concluded 0 ###LEFT-WALL### 29 . 1 it 2 was 2 was 3 concluded 3 concluded 4 that 4 that 11 playing 4 that 16 is 5 in 9 bowlers 5 in 10 , 5 in 11 playing 6 older 8 lawn 7 aged 8 lawn 8 lawn 9 bowlers 11 playing 12 experience 11 playing 14 than 11 playing 16 is 13 rather 14 than 14 than 15 age 16 is 19 determinant 17 a 19 determinant 18 key 19 determinant 19 determinant 20 of 20 of 22 control 21 balance 22 control 22 control 23 during 23 during 28 action 24 the 28 action 25 lawn 27 delivery 26 bowls 27 delivery 27 delivery 28 action background : there are many published surgical techniques for the correction of crow 's feet deformity , but subsequent contour irregularities and early recurrence are often reported . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 28 . 2 : 3 there 2 : 4 are 2 : 18 but 3 there 4 are 4 are 8 techniques 5 many 8 techniques 6 published 8 techniques 7 surgical 8 techniques 8 techniques 9 for 9 for 11 correction 10 the 11 correction 11 correction 12 of 12 of 16 deformity 13 crow 14 's 14 's 16 deformity 15 feet 16 deformity 17 , 18 but 18 but 22 and 18 but 27 reported 19 subsequent 20 contour 20 contour 21 irregularities 21 irregularities 22 and 22 and 24 recurrence 22 and 25 are 23 early 24 recurrence 25 are 27 reported 26 often 27 reported objective : the authors present a radiofrequency ( rf ) technique to treat crow 's feet that can prevent complications while simultaneously maintaining long - term results . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 15 's 0 ###LEFT-WALL### 28 . 2 : 4 authors 2 : 15 's 3 the 4 authors 4 authors 5 present 5 present 7 radiofrequency 6 a 7 radiofrequency 7 radiofrequency 9 rf 8 ( 9 rf 9 rf 10 ) 11 technique 12 to 11 technique 15 's 12 to 14 crow 13 treat 14 crow 15 's 16 feet 16 feet 17 that 16 feet 18 can 17 that 18 can 18 can 19 prevent 19 prevent 20 complications 19 prevent 21 while 21 while 23 maintaining 22 simultaneously 23 maintaining 23 maintaining 27 results 24 long 25 - 24 long 26 term 26 term 27 results methods : from april 2010 to february 2012 , a total of 52 consecutive patients ( 3 men and 49 women ) underwent surgical correction of crow 's feet with an rf current . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 9 , 0 ###LEFT-WALL### 34 . 1 methods 2 : 2 : 3 from 2 : 6 to 3 from 4 april 4 april 5 2010 6 to 7 february 7 february 8 2012 9 , 11 total 9 , 23 underwent 10 a 11 total 11 total 12 of 11 total 23 underwent 12 of 15 patients 13 52 15 patients 14 consecutive 15 patients 15 patients 19 and 16 ( 19 and 17 3 18 men 18 men 19 and 19 and 21 women 19 and 22 ) 20 49 21 women 23 underwent 25 correction 24 surgical 25 correction 25 correction 26 of 25 correction 30 with 26 of 29 feet 27 crow 28 's 28 's 29 feet 30 with 33 current 31 an 33 current 32 rf 33 current following elevation of the skin flap in the temporal area , the lateral portion of the orbicularis oculi muscle was partially elevated and splayed . 0 ###LEFT-WALL### 14 portion 0 ###LEFT-WALL### 20 was 0 ###LEFT-WALL### 25 . 1 following 2 elevation 1 following 7 in 1 following 11 , 1 following 14 portion 2 elevation 3 of 3 of 6 flap 4 the 6 flap 5 skin 6 flap 7 in 10 area 8 the 10 area 9 temporal 10 area 12 the 14 portion 13 lateral 14 portion 14 portion 15 of 14 portion 20 was 15 of 17 orbicularis 16 the 17 orbicularis 17 orbicularis 18 oculi 17 orbicularis 19 muscle 18 oculi 19 muscle 20 was 23 and 21 partially 22 elevated 22 elevated 23 and 23 and 24 splayed then the rf current was applied to the elevated muscle flap until the target temperature of 60 °c to 80 °c was reached . 0 ###LEFT-WALL### 4 current 0 ###LEFT-WALL### 6 applied 1 then 4 current 2 the 4 current 3 rf 4 current 4 current 5 was 5 was 6 applied 6 applied 7 to 6 applied 12 until 7 to 11 flap 8 the 11 flap 9 elevated 10 muscle 10 muscle 11 flap 12 until 15 temperature 12 until 23 reached 13 the 15 temperature 14 target 15 temperature 15 temperature 16 of 15 temperature 22 was 16 of 19 to 17 60 18 °c 18 °c 19 to 19 to 21 °c 20 80 21 °c 22 was 23 reached 23 reached 24 . clinical outcomes were observed through photographs with patients in a natural smiling position . 0 ###LEFT-WALL### 2 outcomes 0 ###LEFT-WALL### 4 observed 0 ###LEFT-WALL### 14 . 1 clinical 2 outcomes 2 outcomes 3 were 3 were 4 observed 4 observed 5 through 4 observed 7 with 4 observed 9 in 5 through 6 photographs 7 with 8 patients 9 in 13 position 10 a 11 natural 10 a 13 position 11 natural 13 position 12 smiling 13 position results : mean ( sd ) patient age was 52.7 ( 2.2 [ )(years ( range , 31 - 73 years ) . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 8 age 2 : 9 was 2 : 23 . 3 mean 5 sd 3 mean 8 age 4 ( 5 sd 5 sd 6 ) 7 patient 8 age 8 age 9 was 9 was 10 52.7 10 52.7 14 )(years 10 52.7 21 years 11 ( 14 )(years 12 2.2 14 )(years 14 )(years 16 range 14 )(years 17 , 15 ( 16 range 16 range 17 , 17 , 21 years 18 31 19 - 19 - 20 73 19 - 21 years 21 years 22 ) patients were followed postoperatively during a mean period of 23 months ( range , 15 - 36 months ) . 0 ###LEFT-WALL### 1 patients 0 ###LEFT-WALL### 3 followed 0 ###LEFT-WALL### 20 . 1 patients 2 were 2 were 3 followed 3 followed 4 postoperatively 3 followed 5 during 3 followed 16 - 5 during 8 period 6 a 7 mean 6 a 8 period 7 mean 8 period 8 period 9 of 9 of 11 months 10 23 11 months 11 months 13 range 12 ( 13 range 13 range 14 , 14 , 16 - 15 15 16 - 16 - 18 months 16 - 19 ) 17 36 18 months there were no recurrences of crow 's feet during the [follow] [-] up period . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 were 0 ###LEFT-WALL### 15 . 1 there 2 were 2 were 4 recurrences 3 no 4 recurrences 4 recurrences 5 of 5 of 8 feet 6 crow 7 's 7 's 8 feet 8 feet 9 during 9 during 14 period 10 the 14 period 13 up 14 period no major complications were noted . 0 ###LEFT-WALL### 3 complications 0 ###LEFT-WALL### 5 noted 0 ###LEFT-WALL### 6 . 1 no 3 complications 2 major 3 complications 3 complications 4 were 4 were 5 noted conclusions : the main advantage of this surgical technique is preserving continuity of the orbicularis oculi muscle while selectively decreasing muscle tone . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 5 advantage 2 : 10 is 2 : 23 . 3 the 4 main 3 the 5 advantage 5 advantage 6 of 5 advantage 10 is 6 of 9 technique 7 this 8 surgical 8 surgical 9 technique 10 is 11 preserving 11 preserving 12 continuity 12 continuity 13 of 13 of 15 orbicularis 14 the 15 orbicularis 15 orbicularis 16 oculi 15 orbicularis 17 muscle 16 oculi 17 muscle 17 muscle 18 while 18 while 20 decreasing 19 selectively 20 decreasing 20 decreasing 22 tone 21 muscle 22 tone hence , this technique may prevent any contour irregularities . 0 ###LEFT-WALL### 4 technique 0 ###LEFT-WALL### 6 prevent 0 ###LEFT-WALL### 10 . 1 hence 2 , 1 hence 4 technique 3 this 4 technique 4 technique 5 may 5 may 6 prevent 6 prevent 9 irregularities 7 any 9 irregularities 8 contour 9 irregularities the rf current causes irreversible muscle fibrosis , which in turn provides long - lasting results . 0 ###LEFT-WALL### 7 fibrosis 0 ###LEFT-WALL### 8 , 0 ###LEFT-WALL### 17 . 1 the 7 fibrosis 2 rf 7 fibrosis 3 current 4 causes 4 causes 7 fibrosis 5 irreversible 6 muscle 6 muscle 7 fibrosis 8 , 9 which 8 , 12 provides 9 which 12 provides 10 in 11 turn 11 turn 12 provides 12 provides 16 results 13 long 14 - 13 long 16 results 15 lasting 16 results while the early results of this series show promising long - term efficacy and a good safety profile , the small number of patients and short - term follow - up period warrant further study . 0 ###LEFT-WALL### 31 up 0 ###LEFT-WALL### 36 . 1 while 4 results 1 while 30 - 1 while 31 up 2 the 4 results 3 early 4 results 4 results 5 of 4 results 9 promising 5 of 8 show 6 this 8 show 7 series 8 show 9 promising 25 and 9 promising 29 follow 10 long 11 - 10 long 12 term 12 term 13 efficacy 13 efficacy 14 and 14 and 18 profile 14 and 19 , 15 a 18 profile 16 good 17 safety 17 safety 18 profile 19 , 22 number 19 , 25 and 20 the 22 number 21 small 22 number 22 number 23 of 23 of 24 patients 25 and 28 term 25 and 29 follow 26 short 27 - 26 short 28 term 31 up 35 study 32 period 35 study 33 warrant 35 study 34 further 35 study the purpose of this study was to explore the subjective experience of older adults interacting with both virtual and real environments . 0 ###LEFT-WALL### 2 purpose 0 ###LEFT-WALL### 22 . 1 the 2 purpose 2 purpose 3 of 2 purpose 6 was 3 of 5 study 4 this 5 study 6 was 7 to 6 was 8 explore 7 to 8 explore 8 explore 11 experience 8 explore 16 with 9 the 11 experience 10 subjective 11 experience 11 experience 12 of 11 experience 15 interacting 12 of 14 adults 13 older 14 adults 16 with 21 environments 17 both 21 environments 18 virtual 19 and 19 and 20 real 19 and 21 environments thirty healthy older adults engaged with real and virtual tasks of similar motor demands : reaching to a target in standing and stepping stance . 0 ###LEFT-WALL### 4 adults 0 ###LEFT-WALL### 5 engaged 0 ###LEFT-WALL### 15 : 0 ###LEFT-WALL### 25 . 1 thirty 4 adults 2 healthy 4 adults 3 older 4 adults 4 adults 5 engaged 5 engaged 6 with 5 engaged 10 tasks 6 with 8 and 7 real 8 and 8 and 9 virtual 10 tasks 11 of 11 of 14 demands 12 similar 13 motor 13 motor 14 demands 15 : 16 reaching 16 reaching 17 to 16 reaching 20 in 17 to 19 target 18 a 19 target 20 in 22 and 21 standing 22 and 22 and 24 stance 23 stepping 24 stance immersive tendencies and absorption scales were administered before the session . 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 7 administered 0 ###LEFT-WALL### 11 . 1 immersive 2 tendencies 2 tendencies 3 and 3 and 5 scales 3 and 6 were 4 absorption 5 scales 6 were 7 administered 7 administered 8 before 8 before 10 session 9 the 10 session game engagement and experience questionnaires were completed after each task , followed by a semistructured interview at the end of the testing session . 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 11 , 0 ###LEFT-WALL### 24 . 1 game 2 engagement 2 engagement 3 and 3 and 5 questionnaires 3 and 11 , 4 experience 5 questionnaires 6 were 7 completed 6 were 11 , 7 completed 8 after 8 after 10 task 9 each 10 task 11 , 12 followed 12 followed 13 by 12 followed 17 at 13 by 16 interview 14 a 16 interview 15 semistructured 16 interview 17 at 19 end 18 the 19 end 19 end 20 of 20 of 23 session 21 the 23 session 22 testing 23 session data were analyzed respectively using paired [t] tests and grounded theory methodology . 0 ###LEFT-WALL### 1 data 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 13 . 1 data 9 and 2 were 3 analyzed 2 were 9 and 3 analyzed 4 respectively 3 analyzed 5 using 5 using 8 tests 6 paired 8 tests 9 and 10 grounded 9 and 12 methodology 11 theory 12 methodology participants preferred the virtual task over the real task . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 2 preferred 0 ###LEFT-WALL### 10 . 1 participants 2 preferred 2 preferred 5 task 2 preferred 6 over 3 the 5 task 4 virtual 5 task 6 over 9 task 7 the 9 task 8 real 9 task they also reported an increase in presence and absorption with the virtual task , describing an external focus of attention . 0 ###LEFT-WALL### 1 they 0 ###LEFT-WALL### 3 reported 1 they 3 reported 2 also 3 reported 3 reported 5 increase 3 reported 6 in 3 reported 10 with 4 an 5 increase 6 in 8 and 7 presence 8 and 8 and 9 absorption 10 with 13 task 11 the 13 task 12 virtual 13 task 13 task 15 describing 14 , 15 describing 15 describing 18 focus 15 describing 21 . 16 an 17 external 16 an 18 focus 17 external 18 focus 18 focus 19 of 19 of 20 attention findings will be used to inform future development of appropriate game - based balance training applications that could be embedded in the home or community settings as part of evidence - based fall prevention programs . 0 ###LEFT-WALL### 3 be 0 ###LEFT-WALL### 31 - 1 findings 2 will 2 will 3 be 3 be 4 used 4 used 5 to 4 used 21 in 5 to 6 inform 6 inform 8 development 7 future 8 development 8 development 9 of 8 development 15 training 8 development 17 that 8 development 18 could 9 of 14 balance 10 appropriate 14 balance 11 game 12 - 11 game 14 balance 13 based 14 balance 15 training 16 applications 17 that 18 could 18 could 19 be 19 be 20 embedded 21 in 24 or 22 the 23 home 23 home 24 or 24 or 26 settings 24 or 27 as 25 community 26 settings 27 as 28 part 28 part 29 of 29 of 30 evidence 31 - 35 programs 31 - 36 . 32 based 35 programs 33 fall 35 programs 34 prevention 35 programs background : cardiovascular disease is 1 of the most common age - related diseases , [and] also 1 of the most common causes of death in the general population . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 4 disease 2 : 5 is 3 cardiovascular 4 disease 4 disease 5 is 5 is 6 1 6 1 7 of 6 1 14 diseases 6 1 18 1 7 of 11 age 8 the 11 age 9 most 10 common 10 common 11 age 12 - 14 diseases 13 related 14 diseases 14 diseases 15 , 15 , 17 also 15 , 18 1 18 1 19 of 18 1 30 . 19 of 23 causes 20 the 21 most 21 most 23 causes 22 common 23 causes 23 causes 24 of 24 of 25 death 25 death 26 in 26 in 29 population 27 the 29 population 28 general 29 population we tested the hypothesis that visible age - related signs associate with risk of ischemic heart disease ( ihd ) , myocardial infarction ( mi ) , and death in the general population , independent [of] chronological age . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 tested 0 ###LEFT-WALL### 8 - 0 ###LEFT-WALL### 39 . 1 we 2 tested 2 tested 7 age 3 the 7 age 4 hypothesis 7 age 5 that 6 visible 6 visible 7 age 8 - 10 signs 8 - 11 associate 8 - 34 , 9 related 10 signs 10 signs 11 associate 11 associate 12 with 11 associate 30 in 12 with 28 and 13 risk 14 of 13 risk 28 and 14 of 17 disease 15 ischemic 16 heart 16 heart 17 disease 17 disease 19 ihd 17 disease 23 infarction 18 ( 19 ihd 19 ihd 20 ) 21 , 23 infarction 22 myocardial 23 infarction 23 infarction 25 mi 23 infarction 27 , 24 ( 25 mi 25 mi 26 ) 27 , 28 and 28 and 29 death 30 in 33 population 31 the 33 population 32 general 33 population 34 , 38 age 35 independent 38 age 37 chronological 38 age during these 35 years [of] follow - up , 3401 participants developed ihd and 1708 developed mi . 0 ###LEFT-WALL### 6 follow 0 ###LEFT-WALL### 7 - 1 during 4 years 1 during 6 follow 2 these 3 35 3 35 4 years 7 - 11 participants 7 - 12 developed 7 - 14 and 7 - 18 . 8 up 9 , 8 up 11 participants 10 3401 11 participants 11 participants 12 developed 12 developed 13 ihd 14 and 15 1708 14 and 16 developed 15 1708 16 developed 16 developed 17 mi presence of frontoparietal baldness , crown top baldness , earlobe crease , and xanthelasmata was associated with increased risk of ihd or mi after multifactorial adjustment for chronological age and well - known cardiovascular risk factors . 0 ###LEFT-WALL### 1 presence 0 ###LEFT-WALL### 16 associated 1 presence 2 of 1 presence 15 was 2 of 13 and 3 frontoparietal 4 baldness 4 baldness 5 , 5 , 8 baldness 5 , 9 , 6 crown 8 baldness 7 top 8 baldness 9 , 11 crease 9 , 13 and 10 earlobe 11 crease 12 , 13 and 13 and 14 xanthelasmata 15 was 16 associated 16 associated 17 with 16 associated 24 after 17 with 19 risk 18 increased 19 risk 19 risk 20 of 20 of 22 or 21 ihd 22 or 22 or 23 mi 24 after 26 adjustment 25 multifactorial 26 adjustment 26 adjustment 27 for 26 adjustment 36 factors 27 for 30 and 28 chronological 29 age 29 age 30 and 30 and 31 well 32 - 36 factors 33 known 36 factors 34 cardiovascular 36 factors 35 risk 36 factors 36 factors 37 . in all age groups in both women and men , absolute 10 [-] year risk of ihd and mi increased with increasing number of visible age - related signs . 0 ###LEFT-WALL### 3 age 0 ###LEFT-WALL### 4 groups 0 ###LEFT-WALL### 28 related 0 ###LEFT-WALL### 30 . 1 in 2 all 1 in 3 age 3 age 4 groups 4 groups 5 in 5 in 8 and 6 both 7 women 7 women 8 and 8 and 23 number 8 and 24 of 9 men 10 , 10 , 15 risk 10 , 18 and 11 absolute 15 risk 12 10 14 year 14 year 15 risk 15 risk 16 of 16 of 17 ihd 18 and 19 mi 18 and 20 increased 18 and 21 with 18 and 23 number 21 with 22 increasing 24 of 26 age 25 visible 26 age 27 - 28 related 28 related 29 signs this is the first prospective study to show that looking old for your age is a marker of poor cardiovascular health . 0 ###LEFT-WALL### 1 this 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 22 . 1 this 2 is 2 is 6 study 3 the 6 study 4 first 6 study 5 prospective 6 study 6 study 7 to 6 study 8 show 7 to 8 show 8 show 9 that 9 that 10 looking 9 that 15 is 10 looking 11 old 10 looking 15 is 11 old 12 for 12 for 14 age 13 your 14 age 15 is 17 marker 16 a 17 marker 17 marker 18 of 18 of 21 health 19 poor 21 health 20 cardiovascular 21 health many clinical and animal studies demonstrate the importance of long - chain polyunsaturated fatty acids ( lcpufa ) in neural development and neurodegeneration . 0 ###LEFT-WALL### 5 studies 0 ###LEFT-WALL### 6 demonstrate 0 ###LEFT-WALL### 24 . 1 many 5 studies 2 clinical 3 and 3 and 4 animal 3 and 5 studies 5 studies 6 demonstrate 6 demonstrate 8 importance 6 demonstrate 19 in 7 the 8 importance 8 importance 9 of 9 of 15 acids 10 long 11 - 10 long 12 chain 12 chain 15 acids 13 polyunsaturated 15 acids 14 fatty 15 acids 15 acids 17 lcpufa 16 ( 17 lcpufa 17 lcpufa 18 ) 19 in 22 and 20 neural 21 development 21 development 22 and 22 and 23 neurodegeneration this review will focus on involvement of lcpufa from genesis to senescence . 0 ###LEFT-WALL### 2 review 0 ###LEFT-WALL### 4 focus 0 ###LEFT-WALL### 13 . 1 this 2 review 2 review 3 will 3 will 4 focus 4 focus 5 on 4 focus 11 to 5 on 6 involvement 6 involvement 7 of 7 of 8 lcpufa 8 lcpufa 9 from 9 from 10 genesis 11 to 12 senescence the lcpufa docosahexaenoic acid and arachidonic acid are important components of neuronal membranes , while eicosapentaenoic acid , docosahexaenoic acid , and arachidonic acid also affect cardiovascular health and inflammation . 0 ###LEFT-WALL### 7 acid 0 ###LEFT-WALL### 8 are 0 ###LEFT-WALL### 14 , 0 ###LEFT-WALL### 31 . 1 the 7 acid 2 lcpufa 7 acid 3 docosahexaenoic 7 acid 4 acid 5 and 5 and 6 arachidonic 5 and 7 acid 7 acid 8 are 8 are 10 components 9 important 10 components 10 components 11 of 11 of 13 membranes 12 neuronal 13 membranes 14 , 22 and 14 , 26 affect 15 while 16 eicosapentaenoic 15 while 22 and 17 acid 18 , 18 , 20 acid 18 , 22 and 19 docosahexaenoic 20 acid 21 , 22 and 22 and 24 acid 22 and 26 affect 23 arachidonic 24 acid 25 also 26 affect 26 affect 29 and 27 cardiovascular 28 health 28 health 29 and 29 and 30 inflammation in neural development , lcpufa deficiency can lead to severe disorders like schizophrenia and attention deficit hyperactivity disorder . 0 ###LEFT-WALL### 6 deficiency 0 ###LEFT-WALL### 8 lead 0 ###LEFT-WALL### 19 . 1 in 3 development 1 in 4 , 1 in 6 deficiency 2 neural 3 development 5 lcpufa 6 deficiency 6 deficiency 7 can 7 can 8 lead 8 lead 9 to 8 lead 12 like 9 to 11 disorders 10 severe 11 disorders 12 like 14 and 13 schizophrenia 14 and 14 and 18 disorder 15 attention 18 disorder 16 deficit 18 disorder 17 hyperactivity 18 disorder perinatal lcpufa supplementation demonstrated beneficial effects in neural development in humans and rodents resulting in improved cognition and sensorimotor integration . 0 ###LEFT-WALL### 3 supplementation 0 ###LEFT-WALL### 4 demonstrated 0 ###LEFT-WALL### 21 . 1 perinatal 2 lcpufa 2 lcpufa 3 supplementation 3 supplementation 4 demonstrated 4 demonstrated 6 effects 4 demonstrated 10 in 5 beneficial 6 effects 6 effects 7 in 7 in 9 development 8 neural 9 development 10 in 18 and 11 humans 12 and 12 and 13 rodents 12 and 14 resulting 12 and 15 in 12 and 18 and 15 in 17 cognition 16 improved 17 cognition 18 and 20 integration 19 sensorimotor 20 integration in normal aging , the effect of lcpufa on prevention of cognitive impairment will be discussed . 0 ###LEFT-WALL### 6 effect 0 ###LEFT-WALL### 16 discussed 0 ###LEFT-WALL### 17 . 1 in 3 aging 1 in 4 , 1 in 6 effect 2 normal 3 aging 5 the 6 effect 6 effect 7 of 6 effect 14 will 7 of 8 lcpufa 8 lcpufa 9 on 9 on 10 prevention 10 prevention 11 of 11 of 13 impairment 12 cognitive 13 impairment 14 will 15 be 15 be 16 discussed lcpufa are important for neuronal membrane integrity and function , and also [contribute] in prevention of brain hypoperfusion . 0 ###LEFT-WALL### 1 lcpufa 0 ###LEFT-WALL### 2 are 0 ###LEFT-WALL### 19 . 1 lcpufa 2 are 2 are 3 important 3 important 11 and 4 for 8 and 4 for 11 and 5 neuronal 6 membrane 6 membrane 7 integrity 7 integrity 8 and 8 and 9 function 10 , 11 and 11 and 12 also 11 and 14 in 14 in 15 prevention 15 prevention 16 of 16 of 18 hypoperfusion 17 brain 18 hypoperfusion cerebral perfusion can be compromised as result of obesity , cerebrovascular disease , hypertension , or diabetes mellitus type 2 . 0 ###LEFT-WALL### 1 cerebral 0 ###LEFT-WALL### 5 compromised 0 ###LEFT-WALL### 21 . 1 cerebral 2 perfusion 1 cerebral 4 be 1 cerebral 5 compromised 2 perfusion 3 can 3 can 4 be 5 compromised 6 as 6 as 16 or 7 result 8 of 7 result 10 , 8 of 9 obesity 10 , 12 disease 10 , 13 , 11 cerebrovascular 12 disease 13 , 14 hypertension 13 , 16 or 15 , 16 or 16 or 19 type 17 diabetes 19 type 18 mellitus 19 type 19 type 20 2 last , we will focus on the role of lcpufa in most common neurodegenerative diseases like alzheimer 's disease and parkinson 's disease . 0 ###LEFT-WALL### 2 , 0 ###LEFT-WALL### 24 . 1 last 2 , 2 , 5 focus 3 we 4 will 4 will 5 focus 5 focus 6 on 5 focus 11 in 6 on 8 role 7 the 8 role 8 role 9 of 9 of 10 lcpufa 11 in 15 diseases 12 most 13 common 13 common 15 diseases 14 neurodegenerative 15 diseases 15 diseases 16 like 16 like 20 and 17 alzheimer 18 's 18 's 19 disease 19 disease 20 and 20 and 23 disease 21 parkinson 22 's 22 's 23 disease these disorders are characterized by impaired cognition and connectivity and both clinical and animal supplementation studies have shown the potential of lcpufa to decrease neurodegeneration and inflammation . 0 ###LEFT-WALL### 2 disorders 0 ###LEFT-WALL### 4 characterized 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 28 . 1 these 2 disorders 2 disorders 3 are 3 are 4 characterized 4 characterized 5 by 5 by 8 and 6 impaired 7 cognition 7 cognition 8 and 8 and 9 connectivity 10 and 13 and 10 and 18 shown 11 both 13 and 12 clinical 13 and 13 and 14 animal 13 and 15 supplementation 13 and 16 studies 13 and 17 have 15 supplementation 16 studies 17 have 18 shown 18 shown 20 potential 18 shown 26 and 19 the 20 potential 20 potential 21 of 21 of 22 lcpufa 22 lcpufa 23 to 23 to 25 neurodegeneration 24 decrease 25 neurodegeneration 26 and 27 inflammation this review shows that lcpufa are essential throughout life . 0 ###LEFT-WALL### 2 review 0 ###LEFT-WALL### 3 shows 0 ###LEFT-WALL### 10 . 1 this 2 review 2 review 3 shows 3 shows 4 that 4 that 5 lcpufa 4 that 6 are 5 lcpufa 6 are 6 are 7 essential 7 essential 8 throughout 8 throughout 9 life the goal of this study was to examine the association between affective development , puberty , and gender using the [startle] reflex as a marker of defensive mechanisms . 0 ###LEFT-WALL### 2 goal 0 ###LEFT-WALL### 29 . 1 the 2 goal 2 goal 3 of 2 goal 6 was 3 of 5 study 4 this 5 study 6 was 7 to 6 was 8 examine 7 to 8 examine 8 examine 10 association 8 examine 11 between 8 examine 19 using 8 examine 23 as 9 the 10 association 11 between 17 and 12 affective 13 development 13 development 14 , 14 , 15 puberty 14 , 17 and 16 , 17 and 17 and 18 gender 19 using 22 reflex 20 the 22 reflex 23 as 25 marker 24 a 25 marker 25 marker 26 of 26 of 28 mechanisms 27 defensive 28 mechanisms thirty - one male and thirty - five female adolescents aged ten to thirteen participated in a prospective study with up to five assessments . 0 ###LEFT-WALL### 1 thirty 0 ###LEFT-WALL### 2 - 2 - 5 and 2 - 15 participated 2 - 25 . 3 one 4 male 4 male 5 and 5 and 10 adolescents 5 and 11 aged 5 and 15 participated 6 thirty 7 - 7 - 8 five 7 - 10 adolescents 9 female 10 adolescents 11 aged 13 to 12 ten 13 to 13 to 14 thirteen 15 participated 16 in 15 participated 20 with 16 in 19 study 17 a 18 prospective 17 a 19 study 18 prospective 19 study 20 with 24 assessments 21 up 22 to 22 to 23 five 23 five 24 assessments longitudinal analyses revealed a significant effect of sex , with girls showing stronger fear - potentiation at all pubertal stages . 0 ###LEFT-WALL### 2 analyses 0 ###LEFT-WALL### 3 revealed 1 longitudinal 2 analyses 2 analyses 3 revealed 3 revealed 6 effect 3 revealed 10 with 4 a 5 significant 4 a 6 effect 5 significant 6 effect 6 effect 7 of 7 of 8 sex 9 , 10 with 10 with 11 girls 10 with 21 . 11 girls 12 showing 11 girls 16 potentiation 12 showing 14 fear 13 stronger 14 fear 15 - 16 potentiation 16 potentiation 17 at 16 potentiation 21 . 17 at 20 stages 18 all 20 stages 19 pubertal 20 stages post [hoc] tests revealed that fear - potentiation increased in girls but not boys over the course of puberty . 0 ###LEFT-WALL### 3 tests 0 ###LEFT-WALL### 4 revealed 0 ###LEFT-WALL### 7 - 1 post 3 tests 3 tests 4 revealed 4 revealed 6 fear 5 that 6 fear 7 - 8 potentiation 7 - 9 increased 7 - 20 . 8 potentiation 9 increased 9 increased 10 in 9 increased 12 but 9 increased 15 over 10 in 11 girls 12 but 13 not 12 but 14 boys 15 over 17 course 16 the 17 course 17 course 18 of 18 of 19 puberty furthermore , baseline [startle] decreased over the course of puberty . 0 ###LEFT-WALL### 3 baseline 0 ###LEFT-WALL### 5 decreased 0 ###LEFT-WALL### 11 . 1 furthermore 2 , 1 furthermore 3 baseline 3 baseline 5 decreased 5 decreased 6 over 6 over 8 course 7 the 8 course 8 course 9 of 9 of 10 puberty because age was included as a covariate in all analyses , the puberty effect cannot be accounted for by age . 0 ###LEFT-WALL### 14 effect 0 ###LEFT-WALL### 18 for 0 ###LEFT-WALL### 21 . 1 because 2 age 1 because 4 included 1 because 11 , 1 because 14 effect 2 age 3 was 3 was 4 included 4 included 5 as 4 included 8 in 5 as 7 covariate 6 a 7 covariate 8 in 10 analyses 9 all 10 analyses 12 the 14 effect 13 puberty 14 effect 14 effect 15 cannot 15 cannot 16 be 16 be 18 for 17 accounted 18 for 18 for 19 by 19 by 20 age to the best of our knowledge , this study provides the first evidence for a significant increase in fear - potentiated [startle] across the pubertal transition . 0 ###LEFT-WALL### 9 study 0 ###LEFT-WALL### 10 provides 1 to 3 best 1 to 7 , 1 to 9 study 2 the 3 best 3 best 4 of 4 of 6 knowledge 5 our 6 knowledge 8 this 9 study 9 study 10 provides 10 provides 13 evidence 10 provides 18 in 11 the 12 first 11 the 13 evidence 13 evidence 14 for 14 for 17 increase 15 a 16 significant 15 a 17 increase 16 significant 17 increase 18 in 19 fear 19 fear 21 potentiated 20 - 21 potentiated 21 potentiated 23 across 21 potentiated 27 . 23 across 26 transition 24 the 26 transition 25 pubertal 26 transition attribution of these changes to pubertal status rather than age [has] important implications for our understanding of the neurobiology of anxiety and affect regulation . 0 ###LEFT-WALL### 1 attribution 0 ###LEFT-WALL### 4 changes 0 ###LEFT-WALL### 25 . 1 attribution 2 of 1 attribution 4 changes 2 of 3 these 4 changes 5 to 4 changes 9 than 5 to 7 status 6 pubertal 7 status 8 rather 9 than 9 than 22 and 10 age 13 implications 10 age 22 and 12 important 13 implications 13 implications 14 for 13 implications 17 of 14 for 16 understanding 15 our 16 understanding 17 of 19 neurobiology 18 the 19 neurobiology 19 neurobiology 20 of 20 of 21 anxiety 22 and 23 affect 23 affect 24 regulation [the] effects [of] blade tenderization ( bt ) , two aging methods [(] [dry] ( [d] [ )(and wet ( w ) [ )(, [and] aging time ( 2 and 23 d ) on tenderness , color , and sensory properties of longissimus lumborum muscles from 12 cull holstein cows were evaluated . 0 ###LEFT-WALL### 2 effects 0 ###LEFT-WALL### 4 blade 0 ###LEFT-WALL### 9 , 2 effects 4 blade 4 blade 5 tenderization 5 tenderization 7 bt 6 ( 7 bt 7 bt 8 ) 9 , 18 )(and 10 two 12 methods 11 aging 12 methods 12 methods 18 )(and 15 ( 18 )(and 18 )(and 19 wet 18 )(and 21 w 18 )(and 26 aging 20 ( 21 w 21 w 22 ) 24 )(, 26 aging 26 aging 27 time 26 aging 34 on 27 time 32 d 28 ( 32 d 29 2 30 and 30 and 31 23 30 and 32 d 32 d 33 ) 34 on 35 tenderness 35 tenderness 44 lumborum 36 , 44 lumborum 37 color 39 and 38 , 39 and 39 and 41 properties 39 and 44 lumborum 40 sensory 41 properties 41 properties 42 of 42 of 43 longissimus 44 lumborum 45 muscles 44 lumborum 48 cull 44 lumborum 53 . 45 muscles 46 from 45 muscles 48 cull 46 from 47 12 48 cull 49 holstein 49 holstein 50 cows 49 holstein 51 were 49 holstein 52 evaluated 50 cows 51 were dry - aged loins had higher combined trim and aging losses than control [(] c [ )(for both [d] - and w - aging , mostly because of excess trim losses . 0 ###LEFT-WALL### 4 loins 0 ###LEFT-WALL### 5 had 0 ###LEFT-WALL### 32 . 1 dry 2 - 1 dry 4 loins 3 aged 4 loins 4 loins 5 had 5 had 9 and 5 had 12 than 5 had 26 mostly 6 higher 8 trim 7 combined 8 trim 8 trim 9 and 9 and 11 losses 10 aging 11 losses 12 than 13 control 12 than 17 )(for 13 control 15 c 17 )(for 21 and 18 both 21 and 20 - 21 and 21 and 22 w 21 and 24 aging 23 - 24 aging 24 aging 25 , 26 mostly 28 of 27 because 28 of 28 of 31 losses 29 excess 31 losses 30 trim 31 losses bt steaks had wbsf of 33.13 n while [c] steaks had wbsf of 41.46 n ( p=0.09 ) . 0 ###LEFT-WALL### 2 steaks 0 ###LEFT-WALL### 3 had 0 ###LEFT-WALL### 19 . 1 bt 2 steaks 2 steaks 3 had 3 had 4 wbsf 3 had 8 while 4 wbsf 5 of 5 of 7 n 6 33.13 7 n 8 while 10 steaks 8 while 11 had 10 steaks 11 had 11 had 12 wbsf 12 wbsf 13 of 12 wbsf 17 p=0.09 13 of 15 n 14 41.46 15 n 16 ( 17 p=0.09 17 p=0.09 18 ) aging decreased wbsf . 0 ###LEFT-WALL### 1 aging 0 ###LEFT-WALL### 2 decreased 0 ###LEFT-WALL### 4 . 1 aging 2 decreased 2 decreased 3 wbsf blade tenderized steaks had higher cook loss than [c] steaks . 0 ###LEFT-WALL### 3 steaks 0 ###LEFT-WALL### 4 had 0 ###LEFT-WALL### 11 . 1 blade 2 tenderized 2 tenderized 3 steaks 3 steaks 4 had 4 had 7 loss 4 had 8 than 5 higher 6 cook 6 cook 7 loss 8 than 10 steaks aging , w - aging , and bt×w - aging improved myofibrillar [(] sensory ) tenderness scores . 0 ###LEFT-WALL### 10 aging 0 ###LEFT-WALL### 17 scores 0 ###LEFT-WALL### 18 . 1 aging 4 - 1 aging 9 - 1 aging 10 aging 2 , 4 - 3 w 4 - 4 - 7 and 4 - 9 - 5 aging 7 and 6 , 7 and 7 and 8 bt×w 10 aging 16 tenderness 10 aging 17 scores 11 improved 16 tenderness 12 myofibrillar 16 tenderness 14 sensory 15 ) 14 sensory 16 tenderness [aging] and/or bt improves sensory panel tenderness [cull] cow longissimus lumborum steaks . 0 ###LEFT-WALL### 2 and/or 0 ###LEFT-WALL### 4 improves 0 ###LEFT-WALL### 13 . 2 and/or 3 bt 3 bt 4 improves 4 improves 12 steaks 5 sensory 6 panel 6 panel 9 cow 7 tenderness 9 cow 9 cow 12 steaks 10 longissimus 12 steaks 11 lumborum 12 steaks aging and blade tenderization combined can increase tenderness and value of longissimus steaks from [cull] holstein cows . 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 18 . 1 aging 2 and 2 and 8 tenderness 2 and 9 and 3 blade 4 tenderization 4 tenderization 5 combined 5 combined 6 can 6 can 8 tenderness 7 increase 8 tenderness 9 and 10 value 9 and 11 of 11 of 13 steaks 12 longissimus 13 steaks 13 steaks 14 from 14 from 17 cows 16 holstein 17 cows age - related hearing loss ( presbycusis ) is caused mainly by the hypofunction of the inner ear , but recent findings point also toward a central component of presbycusis . 0 ###LEFT-WALL### 1 age 0 ###LEFT-WALL### 3 related 0 ###LEFT-WALL### 20 but 0 ###LEFT-WALL### 31 . 2 - 3 related 3 related 4 hearing 3 related 11 mainly 3 related 19 , 4 hearing 5 loss 4 hearing 10 caused 5 loss 7 presbycusis 5 loss 9 is 6 ( 7 presbycusis 7 presbycusis 8 ) 9 is 10 caused 11 mainly 12 by 12 by 14 hypofunction 13 the 14 hypofunction 14 hypofunction 15 of 15 of 18 ear 16 the 18 ear 17 inner 18 ear 19 , 20 but 20 but 22 findings 20 but 23 point 21 recent 22 findings 22 findings 23 point 23 point 24 also 23 point 25 toward 25 toward 28 component 26 a 27 central 26 a 28 component 27 central 28 component 28 component 29 of 29 of 30 presbycusis we used mr morphometry and diffusion tensor imaging ( dti ) with a 3 t mr system with the aim to study the state of the central auditory system in a group of elderly subjects ( >65 [years] ) with mild presbycusis , in a group of elderly subjects with expressed presbycusis and in young controls . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 22 study 1 we 2 used 2 used 5 and 2 used 12 with 2 used 21 to 3 mr 4 morphometry 4 morphometry 5 and 5 and 8 imaging 5 and 10 dti 6 diffusion 8 imaging 7 tensor 8 imaging 9 ( 10 dti 10 dti 11 ) 12 with 17 system 13 a 17 system 14 3 15 t 15 t 17 system 16 mr 17 system 17 system 18 with 18 with 20 aim 19 the 20 aim 21 to 22 study 22 study 24 state 22 study 30 in 23 the 24 state 24 state 25 of 25 of 29 system 26 the 29 system 27 central 29 system 28 auditory 29 system 30 in 32 group 31 a 32 group 32 group 33 of 32 group 40 with 32 group 44 in 33 of 35 subjects 34 elderly 35 subjects 35 subjects 37 >65 36 ( 37 >65 37 >65 39 ) 40 with 42 presbycusis 41 mild 42 presbycusis 43 , 44 in 44 in 49 subjects 44 in 57 . 45 a 46 group 46 group 47 of 46 group 49 subjects 47 of 49 subjects 48 elderly 49 subjects 49 subjects 53 and 50 with 52 presbycusis 50 with 53 and 51 expressed 52 presbycusis 53 and 54 in 54 in 56 controls 55 young 56 controls cortical reconstruction , volumetric segmentation and auditory pathway tractography were performed . 0 ###LEFT-WALL### 6 and 0 ###LEFT-WALL### 10 were 0 ###LEFT-WALL### 12 . 1 cortical 2 reconstruction 2 reconstruction 3 , 3 , 5 segmentation 3 , 6 and 4 volumetric 5 segmentation 6 and 9 tractography 6 and 10 were 7 auditory 8 pathway 8 pathway 9 tractography 10 were 11 performed three parameters were evaluated by morphometry : the volume of the gray matter , the surface area of the gyrus and the thickness of the cortex . 0 ###LEFT-WALL### 2 parameters 0 ###LEFT-WALL### 4 evaluated 0 ###LEFT-WALL### 7 : 0 ###LEFT-WALL### 27 . 1 three 2 parameters 2 parameters 3 were 3 were 4 evaluated 4 evaluated 5 by 5 by 6 morphometry 7 : 9 volume 7 : 14 , 8 the 9 volume 9 volume 10 of 10 of 13 matter 11 the 13 matter 12 gray 13 matter 14 , 21 and 15 the 17 area 16 surface 17 area 17 area 18 of 17 area 21 and 18 of 20 gyrus 19 the 20 gyrus 21 and 23 thickness 21 and 24 of 22 the 23 thickness 24 of 26 cortex 25 the 26 cortex in all experimental groups the surface area and gray matter volume were larger on the left side in heschl 's gyrus and planum temporale and slightly larger in the gyrus frontalis superior , whereas they were larger on the right side in the primary visual cortex . 0 ###LEFT-WALL### 1 in 0 ###LEFT-WALL### 12 were 0 ###LEFT-WALL### 47 . 1 in 4 groups 1 in 12 were 2 all 4 groups 3 experimental 4 groups 5 the 7 area 6 surface 7 area 7 area 8 and 8 and 11 volume 8 and 12 were 9 gray 10 matter 10 matter 11 volume 12 were 13 larger 13 larger 14 on 13 larger 34 whereas 14 on 22 and 15 the 17 side 16 left 17 side 17 side 18 in 17 side 22 and 18 in 21 gyrus 19 heschl 20 's 20 's 21 gyrus 22 and 32 superior 22 and 33 , 23 planum 32 superior 24 temporale 25 and 25 and 27 larger 25 and 32 superior 26 slightly 27 larger 27 larger 28 in 28 in 31 frontalis 29 the 31 frontalis 30 gyrus 31 frontalis 34 whereas 35 they 34 whereas 36 were 35 they 36 were 36 were 37 larger 37 larger 38 on 38 on 41 side 39 the 41 side 40 right 41 side 41 side 42 in 42 in 46 cortex 43 the 46 cortex 44 primary 46 cortex 45 visual 46 cortex almost all of the measured parameters were significantly smaller in the elderly subjects in heschl 's gyrus , planum temporale and gyrus frontalis superior . 0 ###LEFT-WALL### 2 all 0 ###LEFT-WALL### 7 were 0 ###LEFT-WALL### 25 . 1 almost 2 all 2 all 3 of 2 all 7 were 3 of 6 parameters 4 the 6 parameters 5 measured 6 parameters 7 were 8 significantly 7 were 9 smaller 9 smaller 10 in 9 smaller 14 in 10 in 13 subjects 11 the 13 subjects 12 elderly 13 subjects 14 in 21 and 15 heschl 16 's 16 's 17 gyrus 17 gyrus 18 , 18 , 20 temporale 18 , 21 and 19 planum 20 temporale 21 and 24 superior 22 gyrus 24 superior 23 frontalis 24 superior aging did not change the side asymmetry ( laterality [ )(of the gyri . 0 ###LEFT-WALL### 1 aging 0 ###LEFT-WALL### 4 change 1 aging 2 did 2 did 3 not 2 did 4 change 4 change 7 asymmetry 5 the 7 asymmetry 6 side 7 asymmetry 7 asymmetry 9 laterality 8 ( 9 laterality 9 laterality 11 )(of 9 laterality 14 . 11 )(of 13 gyri 12 the 13 gyri in the central part of the auditory pathway above the inferior colliculus , a trend toward an effect of aging was present in the axial vector of the diffusion ( l1 ) [variable] of dti , with increased values observed in elderly subjects . 0 ###LEFT-WALL### 15 trend 0 ###LEFT-WALL### 21 was 1 in 4 part 1 in 13 , 1 in 15 trend 2 the 4 part 3 central 4 part 4 part 5 of 5 of 8 pathway 6 the 8 pathway 7 auditory 8 pathway 8 pathway 9 above 9 above 12 colliculus 10 the 12 colliculus 11 inferior 12 colliculus 14 a 15 trend 15 trend 16 toward 15 trend 19 of 15 trend 21 was 16 toward 18 effect 17 an 18 effect 19 of 20 aging 21 was 22 present 22 present 23 in 23 in 26 vector 24 the 26 vector 25 axial 26 vector 26 vector 27 of 26 vector 31 l1 26 vector 34 of 27 of 29 diffusion 28 the 29 diffusion 30 ( 31 l1 31 l1 32 ) 34 of 35 dti 35 dti 37 with 36 , 37 with 37 with 39 values 37 with 44 . 38 increased 39 values 39 values 40 observed 40 observed 41 in 41 in 43 subjects 42 elderly 43 subjects a trend toward a decrease of l1 on the left side , which was more pronounced in the elderly groups , was observed . 0 ###LEFT-WALL### 2 trend 0 ###LEFT-WALL### 23 observed 0 ###LEFT-WALL### 24 . 1 a 2 trend 2 trend 3 toward 2 trend 22 was 3 toward 5 decrease 4 a 5 decrease 5 decrease 6 of 6 of 7 l1 7 l1 8 on 8 on 11 side 9 the 11 side 10 left 11 side 11 side 13 which 12 , 13 which 13 which 14 was 13 which 21 , 14 was 15 more 14 was 16 pronounced 16 pronounced 17 in 17 in 20 groups 18 the 20 groups 19 elderly 20 groups 22 was 23 observed the effect of hearing loss was present in subjects with expressed presbycusis as a trend toward an increase of the radial vectors ( l2l3 ) in the white matter under heschl 's gyrus . 0 ###LEFT-WALL### 2 effect 0 ###LEFT-WALL### 6 was 0 ###LEFT-WALL### 34 . 1 the 2 effect 2 effect 3 of 2 effect 6 was 3 of 5 loss 4 hearing 5 loss 6 was 7 present 7 present 8 in 7 present 10 with 7 present 13 as 7 present 16 toward 7 present 30 under 8 in 9 subjects 10 with 12 presbycusis 11 expressed 12 presbycusis 13 as 15 trend 14 a 15 trend 16 toward 18 increase 17 an 18 increase 18 increase 19 of 18 increase 26 in 19 of 22 vectors 20 the 22 vectors 21 radial 22 vectors 22 vectors 24 l2l3 23 ( 24 l2l3 24 l2l3 25 ) 26 in 29 matter 27 the 29 matter 28 white 29 matter 30 under 33 gyrus 31 heschl 32 's 32 's 33 gyrus these results suggest that in addition to peripheral changes , changes in the central part of the auditory system in elderly subjects are also present ; however , the extent of hearing loss does not play a significant role in the central changes . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 suggest 0 ###LEFT-WALL### 26 ; 0 ###LEFT-WALL### 44 . 1 these 2 results 2 results 3 suggest 3 suggest 4 that 4 that 11 changes 4 that 23 are 5 in 6 addition 5 in 10 , 5 in 11 changes 6 addition 7 to 7 to 9 changes 8 peripheral 9 changes 11 changes 12 in 11 changes 23 are 12 in 15 part 13 the 15 part 14 central 15 part 15 part 16 of 16 of 19 system 17 the 19 system 18 auditory 19 system 19 system 20 in 20 in 22 subjects 21 elderly 22 subjects 23 are 24 also 23 are 25 present 26 ; 33 loss 26 ; 36 play 27 however 28 , 27 however 33 loss 29 the 30 extent 30 extent 31 of 30 extent 33 loss 31 of 33 loss 32 hearing 33 loss 33 loss 34 does 34 does 35 not 34 does 36 play 36 play 39 role 36 play 40 in 37 a 39 role 38 significant 39 role 40 in 43 changes 41 the 43 changes 42 central 43 changes the differentiation capabilities of mesenchymal stem cells ( mscs ) compromise with age and [with] in vitro passages which could impair the efficacy of cell therapy and tissue engineering . 0 ###LEFT-WALL### 3 capabilities 0 ###LEFT-WALL### 11 compromise 0 ###LEFT-WALL### 14 and 0 ###LEFT-WALL### 30 . 1 the 3 capabilities 2 differentiation 3 capabilities 3 capabilities 4 of 3 capabilities 9 mscs 3 capabilities 11 compromise 4 of 7 cells 5 mesenchymal 6 stem 6 stem 7 cells 8 ( 9 mscs 9 mscs 10 ) 11 compromise 12 with 12 with 13 age 14 and 18 passages 14 and 21 impair 16 in 17 vitro 17 vitro 18 passages 18 passages 19 which 18 passages 20 could 18 passages 21 impair 19 which 20 could 21 impair 23 efficacy 22 the 23 efficacy 23 efficacy 24 of 24 of 27 and 25 cell 26 therapy 26 therapy 27 and 27 and 29 engineering 28 tissue 29 engineering however , how to maintain these capabilities is not fully understood . 0 ###LEFT-WALL### 3 how 0 ###LEFT-WALL### 11 understood 0 ###LEFT-WALL### 12 . 1 however 2 , 1 however 3 how 3 how 4 to 3 how 5 maintain 3 how 8 is 4 to 5 maintain 5 maintain 7 capabilities 6 these 7 capabilities 8 is 9 not 8 is 11 understood 10 fully 11 understood calorie [restriction] ( cr , decreasing caloric intake by 30 - 40 % ) could extend longevity and reduce aging - related diseases . 0 ###LEFT-WALL### 1 calorie 0 ###LEFT-WALL### 18 and 0 ###LEFT-WALL### 22 related 1 calorie 4 cr 1 calorie 6 decreasing 1 calorie 15 could 3 ( 4 cr 4 cr 5 , 5 , 6 decreasing 6 decreasing 8 intake 6 decreasing 9 by 6 decreasing 14 ) 7 caloric 8 intake 9 by 13 % 10 30 11 - 11 - 12 40 11 - 13 % 15 could 18 and 16 extend 17 longevity 16 extend 18 and 18 and 19 reduce 19 reduce 20 aging 21 - 22 related 22 related 23 diseases 22 related 24 . recent studies revealed that cr could influence the lineage determination of stem cells including mscs . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 3 revealed 0 ###LEFT-WALL### 16 . 1 recent 2 studies 2 studies 3 revealed 3 revealed 4 that 4 that 5 cr 4 that 7 influence 5 cr 6 could 6 could 7 influence 7 influence 10 determination 8 the 10 determination 9 lineage 10 determination 10 determination 11 of 11 of 13 cells 12 stem 13 cells 13 cells 14 including 14 including 15 mscs two important mediators of cr might be silent mating type information regulation 2 homolog 1 ( sirt1 ) , a nad [(] [+] ) - dependent deacetylase , and amp - activated protein [kinase] ( ampk ) , [an] energy - sensing kinase . 0 ###LEFT-WALL### 3 mediators 0 ###LEFT-WALL### 7 be 0 ###LEFT-WALL### 44 . 1 two 3 mediators 2 important 3 mediators 3 mediators 4 of 3 mediators 6 might 4 of 5 cr 6 might 7 be 7 be 29 and 8 silent 9 mating 8 silent 29 and 9 mating 14 homolog 10 type 12 regulation 11 information 12 regulation 12 regulation 14 homolog 13 2 14 homolog 14 homolog 15 1 14 homolog 17 sirt1 14 homolog 21 nad 14 homolog 27 deacetylase 16 ( 17 sirt1 17 sirt1 18 ) 19 , 21 nad 20 a 21 nad 21 nad 24 ) 25 - 27 deacetylase 26 dependent 27 deacetylase 27 deacetylase 28 , 29 and 43 kinase 30 amp 33 protein 30 amp 43 kinase 31 - 33 protein 32 activated 33 protein 33 protein 36 ampk 33 protein 40 energy 33 protein 41 - 35 ( 36 ampk 36 ampk 37 ) 38 , 40 energy 40 energy 41 - 42 sensing 43 kinase [evidences] are mounting [that] both sirt1 and ampk play important roles in cell fate determination of mscs . 0 ###LEFT-WALL### 2 are 0 ###LEFT-WALL### 18 . 2 are 11 roles 3 mounting 9 play 5 both 7 and 6 sirt1 7 and 7 and 8 ampk 7 and 9 play 9 play 11 roles 10 important 11 roles 11 roles 12 in 11 roles 16 of 12 in 15 determination 13 cell 15 determination 14 fate 15 determination 16 of 17 mscs herein , we intend to sum up our understanding about the role of sirt1 and ampk in osteogenic and adipogenic potential of mscs . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 intend 0 ###LEFT-WALL### 24 . 1 herein 2 , 1 herein 3 we 3 we 4 intend 4 intend 5 to 4 intend 6 sum 5 to 6 sum 6 sum 7 up 6 sum 9 understanding 6 sum 10 about 6 sum 17 in 8 our 9 understanding 10 about 12 role 11 the 12 role 12 role 13 of 13 of 16 ampk 14 sirt1 15 and 15 and 16 ampk 17 in 21 potential 18 osteogenic 19 and 19 and 20 adipogenic 19 and 21 potential 21 potential 22 of 22 of 23 mscs metabolic process of mscs differentiation and the putative interplay of sirt1 and ampk in this process was also discussed . 0 ###LEFT-WALL### 2 process 0 ###LEFT-WALL### 17 was 0 ###LEFT-WALL### 20 . 1 metabolic 2 process 2 process 3 of 2 process 10 of 2 process 17 was 3 of 6 and 4 mscs 5 differentiation 5 differentiation 6 and 6 and 9 interplay 7 the 9 interplay 8 putative 9 interplay 10 of 13 ampk 11 sirt1 12 and 12 and 13 ampk 13 ampk 14 in 14 in 16 process 15 this 16 process 17 was 19 discussed 18 also 19 discussed human brain [function] undergoes complex transformations across the lifespan . 0 ###LEFT-WALL### 2 brain 0 ###LEFT-WALL### 4 undergoes 0 ###LEFT-WALL### 10 . 1 human 2 brain 2 brain 4 undergoes 4 undergoes 6 transformations 4 undergoes 7 across 5 complex 6 transformations 7 across 9 lifespan 8 the 9 lifespan we employed resting - state functional mri and graph - theory approaches to systematically chart the lifespan trajectory of the topological organization of human whole - brain functional networks in 126 healthy individuals ranging in age from 7 to 85 years . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 employed 1 we 2 employed 2 employed 3 resting 3 resting 8 and 3 resting 12 approaches 4 - 8 and 5 state 7 mri 6 functional 7 mri 7 mri 8 and 8 and 9 graph 8 and 10 - 10 - 12 approaches 11 theory 12 approaches 12 approaches 13 to 12 approaches 15 chart 12 approaches 42 . 13 to 15 chart 14 systematically 15 chart 15 chart 18 trajectory 15 chart 30 in 16 the 18 trajectory 17 lifespan 18 trajectory 18 trajectory 19 of 19 of 22 organization 20 the 22 organization 21 topological 22 organization 22 organization 23 of 23 of 29 networks 24 human 27 brain 25 whole 26 - 25 whole 27 brain 27 brain 29 networks 28 functional 29 networks 30 in 41 years 31 126 35 in 32 healthy 33 individuals 33 individuals 34 ranging 34 ranging 35 in 35 in 41 years 36 age 39 to 36 age 41 years 37 from 39 to 38 7 39 to 39 to 40 85 brain networks were constructed by computing pearson 's correlations in blood - oxygenation - level - dependent temporal fluctuations among 1024 parcellation units followed by graph - based network analyses . 0 ###LEFT-WALL### 2 networks 0 ###LEFT-WALL### 14 - 1 brain 2 networks 2 networks 3 were 3 were 4 constructed 4 constructed 5 by 5 by 6 computing 6 computing 9 correlations 6 computing 10 in 7 pearson 8 's 8 's 9 correlations 10 in 11 blood 11 blood 13 oxygenation 12 - 13 oxygenation 13 oxygenation 14 - 14 - 15 level 14 - 28 based 14 - 31 . 15 level 19 fluctuations 15 level 28 based 16 - 19 fluctuations 17 dependent 19 fluctuations 18 temporal 19 fluctuations 19 fluctuations 20 among 19 fluctuations 27 - 20 among 21 1024 21 1024 23 units 21 1024 26 graph 22 parcellation 23 units 23 units 24 followed 23 units 26 graph 24 followed 25 by 28 based 30 analyses 29 network 30 analyses we observed that the human brain functional connectome exhibited highly preserved [non] - random modular and rich club organization over the entire age range studied . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 observed 0 ###LEFT-WALL### 13 - 0 ###LEFT-WALL### 26 . 1 we 2 observed 2 observed 3 that 3 that 5 human 3 that 6 brain 4 the 5 human 5 human 6 brain 6 brain 8 connectome 7 functional 8 connectome 8 connectome 9 exhibited 8 connectome 11 preserved 10 highly 11 preserved 13 - 19 organization 14 random 19 organization 15 modular 16 and 16 and 17 rich 16 and 18 club 18 club 19 organization 19 organization 20 over 20 over 24 range 21 the 24 range 22 entire 24 range 23 age 24 range 24 range 25 studied further quantitative analyses revealed linear decreases in modularity and inverted - [u] shaped trajectories of local efficiency and rich club architecture . 0 ###LEFT-WALL### 1 further 0 ###LEFT-WALL### 11 - 1 further 3 analyses 2 quantitative 3 analyses 3 analyses 9 and 4 revealed 6 decreases 4 revealed 7 in 4 revealed 9 and 5 linear 6 decreases 7 in 8 modularity 9 and 10 inverted 11 - 18 and 11 - 22 . 13 shaped 14 trajectories 14 trajectories 15 of 14 trajectories 18 and 15 of 17 efficiency 16 local 17 efficiency 18 and 21 architecture 19 rich 20 club 20 club 21 architecture regionally heterogeneous age effects were mainly located in several hubs ( e.g [.] , default [network] , dorsal attention regions ) . 0 ###LEFT-WALL### 4 effects 0 ###LEFT-WALL### 7 located 0 ###LEFT-WALL### 22 . 1 regionally 4 effects 2 heterogeneous 3 age 3 age 4 effects 4 effects 5 were 5 were 7 located 6 mainly 7 located 7 located 8 in 8 in 10 hubs 9 several 10 hubs 10 hubs 15 default 10 hubs 20 regions 11 ( 15 default 12 e.g 14 , 12 e.g 15 default 15 default 17 , 17 , 20 regions 18 dorsal 19 attention 19 attention 20 regions 20 regions 21 ) finally , we observed inverse trajectories of long - and short - distance functional connections , indicating that the reorganization of connectivity concentrates and distributes the brain 's functional networks . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 24 and 0 ###LEFT-WALL### 31 . 1 finally 2 , 1 finally 3 we 3 we 24 and 4 observed 6 trajectories 4 observed 24 and 5 inverse 6 trajectories 6 trajectories 7 of 6 trajectories 17 indicating 7 of 10 and 8 long 10 and 9 - 10 and 10 and 11 short 10 and 15 connections 12 - 15 connections 13 distance 15 connections 14 functional 15 connections 15 connections 16 , 17 indicating 18 that 18 that 20 reorganization 18 that 23 concentrates 19 the 20 reorganization 20 reorganization 21 of 20 reorganization 23 concentrates 21 of 22 connectivity 24 and 25 distributes 25 distributes 30 networks 26 the 27 brain 27 brain 28 's 28 's 30 networks 29 functional 30 networks our results demonstrate topological changes in the whole - brain functional connectome across [nearly] the entire human lifespan , providing insights into the neural substrates underlying individual variations in behavior and cognition . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 demonstrate 0 ###LEFT-WALL### 33 . 1 our 2 results 2 results 3 demonstrate 3 demonstrate 5 changes 3 demonstrate 29 in 4 topological 5 changes 5 changes 6 in 5 changes 20 providing 6 in 8 whole 7 the 8 whole 8 whole 12 connectome 9 - 12 connectome 10 brain 12 connectome 11 functional 12 connectome 12 connectome 13 across 12 connectome 19 , 13 across 18 lifespan 15 the 18 lifespan 16 entire 18 lifespan 17 human 18 lifespan 20 providing 21 insights 21 insights 22 into 21 insights 26 underlying 22 into 25 substrates 23 the 25 substrates 24 neural 25 substrates 26 underlying 28 variations 27 individual 28 variations 29 in 31 and 30 behavior 31 and 31 and 32 cognition these results have important implications for disease connectomics because they provide a baseline for evaluating network impairments in age - related neuropsychiatric disorders . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 have 0 ###LEFT-WALL### 21 related 0 ###LEFT-WALL### 24 . 1 these 2 results 2 results 3 have 3 have 5 implications 3 have 9 because 4 important 5 implications 5 implications 6 for 6 for 8 connectomics 7 disease 8 connectomics 9 because 10 they 9 because 11 provide 10 they 11 provide 11 provide 13 baseline 12 a 13 baseline 13 baseline 14 for 13 baseline 18 in 14 for 15 evaluating 15 evaluating 17 impairments 16 network 17 impairments 18 in 19 age 20 - 21 related 21 related 23 disorders 22 neuropsychiatric 23 disorders the dsm [-] 5 introduces major modifications in the category of mental disorders due to brain lesions compared to the previous dsm versions , which are reviewed in this paper . 0 ###LEFT-WALL### 2 dsm 0 ###LEFT-WALL### 16 brain 1 the 2 dsm 2 dsm 4 5 2 dsm 5 introduces 5 introduces 7 modifications 5 introduces 8 in 6 major 7 modifications 8 in 10 category 9 the 10 category 10 category 11 of 11 of 13 disorders 12 mental 13 disorders 13 disorders 14 due 14 due 15 to 14 due 16 brain 15 to 16 brain 16 brain 17 lesions 16 brain 19 to 17 lesions 18 compared 19 to 23 versions 20 the 21 previous 20 the 23 versions 22 dsm 23 versions 23 versions 25 which 24 , 25 which 25 which 26 are 25 which 31 . 26 are 27 reviewed 27 reviewed 28 in 28 in 30 paper 29 this 30 paper the description of the category major neurocognitive disorder , as a substitute for dementia , seems to fit better for patients and families , and more adapted to many neurodegenerative cognitive disorders for which memory impairment is not predominant . 0 ###LEFT-WALL### 2 description 0 ###LEFT-WALL### 25 and 0 ###LEFT-WALL### 37 is 0 ###LEFT-WALL### 40 . 1 the 2 description 2 description 3 of 2 description 10 as 2 description 16 seems 3 of 8 disorder 4 the 8 disorder 5 category 8 disorder 6 major 8 disorder 7 neurocognitive 8 disorder 9 , 10 as 10 as 12 substitute 10 as 15 , 11 a 12 substitute 12 substitute 13 for 13 for 14 dementia 16 seems 17 to 16 seems 18 fit 17 to 18 fit 18 fit 19 better 18 fit 20 for 20 for 22 and 21 patients 22 and 22 and 23 families 24 , 25 and 25 and 26 more 25 and 27 adapted 26 more 27 adapted 27 adapted 28 to 27 adapted 33 for 28 to 32 disorders 29 many 32 disorders 30 neurodegenerative 32 disorders 31 cognitive 32 disorders 33 for 34 which 34 which 36 impairment 35 memory 36 impairment 36 impairment 37 is 37 is 38 not 37 is 39 predominant 38 not 39 predominant similarly , the introduction of the category of mild neurocognitive disorder appears to be an improvement although some difficulty still remains for distinguishing mild cognitive disorder from normal aging . 0 ###LEFT-WALL### 4 introduction 0 ###LEFT-WALL### 21 remains 0 ###LEFT-WALL### 30 . 1 similarly 2 , 1 similarly 4 introduction 3 the 4 introduction 4 introduction 5 of 4 introduction 12 appears 5 of 7 category 6 the 7 category 7 category 8 of 8 of 11 disorder 9 mild 11 disorder 10 neurocognitive 11 disorder 12 appears 13 to 12 appears 14 be 13 to 14 be 14 be 16 improvement 14 be 17 although 15 an 16 improvement 17 although 19 difficulty 18 some 19 difficulty 19 difficulty 21 remains 20 still 21 remains 21 remains 22 for 22 for 23 distinguishing 23 distinguishing 26 disorder 24 mild 26 disorder 25 cognitive 26 disorder 26 disorder 27 from 27 from 29 aging 28 normal 29 aging the addition of new etiological categories such as fronto - temporal ncd or ncd with lewy bodies should also [to] be considered as a significant improvement . 0 ###LEFT-WALL### 13 or 0 ###LEFT-WALL### 22 considered 0 ###LEFT-WALL### 27 . 1 the 2 addition 2 addition 3 of 2 addition 13 or 3 of 6 categories 4 new 6 categories 5 etiological 6 categories 6 categories 8 as 7 such 8 as 8 as 12 ncd 9 fronto 10 - 9 fronto 12 ncd 11 temporal 12 ncd 13 or 14 ncd 13 or 15 with 13 or 18 should 15 with 17 bodies 16 lewy 17 bodies 18 should 21 be 19 also 21 be 21 be 22 considered 22 considered 23 as 23 as 26 improvement 24 a 25 significant 24 a 26 improvement 25 significant 26 improvement despite these advances [,] to circumscribe the mental disorders due to brain lesions to cognitive deficits and biological mechanisms remains highly questionable [,] and does not provide an adequate care for the patients and families if not complemented by a psychological and environmental approach . 0 ###LEFT-WALL### 24 and 0 ###LEFT-WALL### 45 . 1 despite 3 advances 1 despite 24 and 2 these 3 advances 3 advances 5 to 3 advances 6 circumscribe 3 advances 10 due 5 to 6 circumscribe 6 circumscribe 9 disorders 7 the 9 disorders 8 mental 9 disorders 10 due 11 to 10 due 12 brain 11 to 12 brain 12 brain 13 lesions 12 brain 14 to 14 to 17 and 15 cognitive 16 deficits 16 deficits 17 and 17 and 19 mechanisms 18 biological 19 mechanisms 20 remains 21 highly 20 remains 22 questionable 20 remains 24 and 24 and 25 does 25 does 26 not 25 does 27 provide 27 provide 30 care 27 provide 31 for 27 provide 36 if 27 provide 39 by 28 an 30 care 29 adequate 30 care 31 for 34 and 32 the 33 patients 33 patients 34 and 34 and 35 families 36 if 37 not 37 not 38 complemented 39 by 44 approach 40 a 44 approach 41 psychological 42 and 42 and 43 environmental 42 and 44 approach in aged human , the number of muscle fibers and motor units decreases . 0 ###LEFT-WALL### 1 in 0 ###LEFT-WALL### 2 aged 0 ###LEFT-WALL### 4 , 0 ###LEFT-WALL### 14 . 1 in 2 aged 2 aged 3 human 4 , 6 number 4 , 13 decreases 5 the 6 number 6 number 7 of 6 number 13 decreases 7 of 10 and 8 muscle 9 fibers 9 fibers 10 and 10 and 12 units 11 motor 12 units the remaining motor units lose their functionality ( [decrease] of the discharge frequency , greater fluctuation of the discharge ) particularly those [which] contain type ii [fibers] . 0 ###LEFT-WALL### 4 units 0 ###LEFT-WALL### 5 lose 1 the 2 remaining 1 the 4 units 3 motor 4 units 4 units 5 lose 5 lose 7 functionality 6 their 7 functionality 7 functionality 10 of 8 ( 10 of 10 of 13 frequency 10 of 22 those 10 of 24 contain 10 of 28 . 11 the 13 frequency 12 discharge 13 frequency 13 frequency 16 fluctuation 14 , 16 fluctuation 15 greater 16 fluctuation 16 fluctuation 17 of 16 fluctuation 20 ) 17 of 19 discharge 18 the 19 discharge 21 particularly 22 those 22 those 24 contain 24 contain 25 type 25 type 26 ii the renewal of intracellular proteins declines [which] creates a negative balance between the daily protein losses and the capacities to renew them . 0 ###LEFT-WALL### 2 renewal 0 ###LEFT-WALL### 8 creates 0 ###LEFT-WALL### 23 . 1 the 2 renewal 2 renewal 3 of 2 renewal 8 creates 3 of 6 declines 4 intracellular 5 proteins 5 proteins 6 declines 8 creates 11 balance 9 a 11 balance 10 negative 11 balance 11 balance 12 between 11 balance 20 to 11 balance 21 renew 12 between 17 and 13 the 16 losses 14 daily 15 protein 15 protein 16 losses 16 losses 17 and 17 and 19 capacities 18 the 19 capacities 20 to 21 renew 21 renew 22 them the activity of the protein kinase ( akt ) that stimulates the synthesis of regulation proteins ( mtor , p70s6 , igfbp - 5 ) declines whereas the factors of degradation of proteins ( nf - kappa b ) are activated . 0 ###LEFT-WALL### 2 activity 0 ###LEFT-WALL### 41 activated 0 ###LEFT-WALL### 42 . 1 the 2 activity 2 activity 3 of 2 activity 10 that 2 activity 11 stimulates 2 activity 26 declines 3 of 6 kinase 4 the 6 kinase 5 protein 6 kinase 6 kinase 8 akt 7 ( 8 akt 8 akt 9 ) 10 that 11 stimulates 11 stimulates 13 synthesis 12 the 13 synthesis 13 synthesis 14 of 14 of 16 proteins 15 regulation 16 proteins 16 proteins 20 p70s6 16 proteins 22 igfbp 17 ( 20 p70s6 18 mtor 19 , 18 mtor 20 p70s6 20 p70s6 21 , 21 , 22 igfbp 22 igfbp 24 5 22 igfbp 25 ) 23 - 24 5 24 5 25 ) 26 declines 27 whereas 27 whereas 29 factors 28 the 29 factors 29 factors 30 of 29 factors 37 kappa 29 factors 40 are 30 of 31 degradation 31 degradation 32 of 31 degradation 35 nf 32 of 33 proteins 34 ( 35 nf 35 nf 36 - 36 - 37 kappa 37 kappa 38 b 37 kappa 39 ) 40 are 41 activated besides , the process of activation and proliferation of satellite cells is affected and the production of anabolic hormones and local factors is decreased . 0 ###LEFT-WALL### 4 process 0 ###LEFT-WALL### 13 affected 0 ###LEFT-WALL### 14 and 0 ###LEFT-WALL### 25 . 1 besides 2 , 1 besides 4 process 3 the 4 process 4 process 5 of 4 process 12 is 5 of 7 and 6 activation 7 and 7 and 8 proliferation 7 and 9 of 9 of 11 cells 10 satellite 11 cells 12 is 13 affected 14 and 16 production 14 and 24 decreased 15 the 16 production 16 production 17 of 16 production 23 is 17 of 20 and 18 anabolic 19 hormones 19 hormones 20 and 20 and 22 factors 21 local 22 factors 23 is 24 decreased after a strength training program , muscle [hypertrophy] is linked to the protein synthesis at the level of myosin heavy chain ( mhc ) isoforms in older subjects . 0 ###LEFT-WALL### 7 muscle 0 ###LEFT-WALL### 10 linked 0 ###LEFT-WALL### 29 . 1 after 5 program 1 after 6 , 1 after 7 muscle 2 a 3 strength 2 a 5 program 3 strength 5 program 4 training 5 program 7 muscle 9 is 9 is 10 linked 10 linked 11 to 10 linked 15 at 11 to 14 synthesis 12 the 14 synthesis 13 protein 14 synthesis 15 at 17 level 16 the 17 level 17 level 18 of 17 level 21 chain 17 level 25 isoforms 18 of 19 myosin 20 heavy 21 chain 21 chain 23 mhc 21 chain 25 isoforms 22 ( 23 mhc 23 mhc 24 ) 25 isoforms 26 in 26 in 28 subjects 27 older 28 subjects however , the transcription of the genes that code the mhc [-] i ( slow form ) increases and the transcription of the genes that code the mhc - ii ( fast form ) decreases . 0 ###LEFT-WALL### 4 transcription 0 ###LEFT-WALL### 18 increases 0 ###LEFT-WALL### 19 and 0 ###LEFT-WALL### 36 . 1 however 2 , 1 however 4 transcription 3 the 4 transcription 4 transcription 5 of 4 transcription 18 increases 5 of 7 genes 6 the 7 genes 7 genes 8 that 7 genes 9 code 7 genes 16 form 8 that 9 code 9 code 11 mhc 10 the 11 mhc 11 mhc 13 i 14 ( 16 form 15 slow 16 form 16 form 17 ) 19 and 21 transcription 19 and 35 decreases 20 the 21 transcription 21 transcription 22 of 21 transcription 35 decreases 22 of 24 genes 23 the 24 genes 24 genes 25 that 24 genes 26 code 25 that 26 code 26 code 28 mhc 27 the 28 mhc 28 mhc 30 ii 29 - 30 ii 30 ii 33 form 30 ii 34 ) 31 ( 33 form 32 fast 33 form 33 form 34 ) thus , the transition of the phenotype towards a slower form cannot be inverted by strength training during the advanced in age . 0 ###LEFT-WALL### 4 transition 0 ###LEFT-WALL### 14 inverted 0 ###LEFT-WALL### 23 . 1 thus 2 , 1 thus 4 transition 3 the 4 transition 4 transition 5 of 4 transition 12 cannot 5 of 7 phenotype 6 the 7 phenotype 7 phenotype 8 towards 8 towards 11 form 9 a 11 form 10 slower 11 form 12 cannot 13 be 13 be 14 inverted 14 inverted 15 by 14 inverted 18 during 14 inverted 21 in 15 by 17 training 16 strength 17 training 18 during 20 advanced 19 the 20 advanced 21 in 22 age moreover , strength training enables to decrease the proportion of fibers containing mhc of hybrid form in the process of evolution . 0 ###LEFT-WALL### 4 training 0 ###LEFT-WALL### 5 enables 0 ###LEFT-WALL### 22 . 1 moreover 2 , 1 moreover 4 training 3 strength 4 training 4 training 5 enables 5 enables 6 to 5 enables 9 proportion 6 to 7 decrease 8 the 9 proportion 9 proportion 10 of 9 proportion 12 containing 10 of 11 fibers 12 containing 13 mhc 12 containing 17 in 13 mhc 14 of 14 of 16 form 15 hybrid 16 form 17 in 19 process 18 the 19 process 19 process 20 of 20 of 21 evolution hence , strength training can engender [a] stabilization of the muscular phenotype i.e [.] different isoforms of mhc . 0 ###LEFT-WALL### 4 training 0 ###LEFT-WALL### 6 engender 0 ###LEFT-WALL### 19 . 1 hence 2 , 1 hence 4 training 3 strength 4 training 4 training 5 can 5 can 6 engender 6 engender 8 stabilization 8 stabilization 9 of 8 stabilization 17 of 9 of 16 isoforms 10 the 16 isoforms 11 muscular 12 phenotype 12 phenotype 16 isoforms 13 i.e 16 isoforms 15 different 16 isoforms 17 of 18 mhc in addition , strength training counteracts the noxious effects mentioned above by generating muscular [hypertrophy] thanks to a reactive increase in the production of anabolic hormones . 0 ###LEFT-WALL### 5 training 0 ###LEFT-WALL### 6 counteracts 0 ###LEFT-WALL### 27 . 1 in 2 addition 1 in 3 , 1 in 5 training 4 strength 5 training 5 training 6 counteracts 6 counteracts 9 effects 7 the 9 effects 8 noxious 9 effects 9 effects 10 mentioned 10 mentioned 11 above 10 mentioned 12 by 12 by 13 generating 13 generating 16 thanks 13 generating 21 in 14 muscular 16 thanks 16 thanks 17 to 17 to 20 increase 18 a 19 reactive 18 a 20 increase 19 reactive 20 increase 21 in 23 production 22 the 23 production 23 production 24 of 24 of 26 hormones 25 anabolic 26 hormones a program of aerobic training can induce an increase in the synthesis of arn messengers coding isoforms related to the oxidative metabolism ( mhc - [i] and to a lesser extent mhc - iia ) while [the] transcribed for the type mhc - iix decrease . 0 ###LEFT-WALL### 2 program 0 ###LEFT-WALL### 7 induce 0 ###LEFT-WALL### 18 related 1 a 2 program 2 program 3 of 2 program 6 can 3 of 5 training 4 aerobic 5 training 6 can 7 induce 7 induce 9 increase 7 induce 10 in 8 an 9 increase 10 in 12 synthesis 11 the 12 synthesis 12 synthesis 13 of 12 synthesis 16 coding 13 of 15 messengers 14 arn 15 messengers 17 isoforms 18 related 18 related 27 and 18 related 36 while 18 related 39 for 18 related 46 . 19 to 22 metabolism 19 to 27 and 20 the 22 metabolism 21 oxidative 22 metabolism 22 metabolism 24 mhc 23 ( 24 mhc 24 mhc 25 - 27 and 28 to 28 to 32 mhc 29 a 30 lesser 29 a 32 mhc 30 lesser 31 extent 31 extent 32 mhc 32 mhc 34 iia 33 - 34 iia 34 iia 35 ) 36 while 38 transcribed 39 for 42 mhc 40 the 41 type 41 type 42 mhc 42 mhc 45 decrease 43 - 45 decrease 44 iix 45 decrease 45 decrease 46 . objective : a comprehensive literature review suggests that suicidal behaviour results from a complex interplay between stressful events and vulnerability factors including cognitive deficits . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 25 . 2 : 6 review 2 : 7 suggests 3 a 6 review 4 comprehensive 5 literature 5 literature 6 review 6 review 7 suggests 7 suggests 11 results 8 that 9 suicidal 9 suicidal 10 behaviour 10 behaviour 11 results 11 results 12 from 11 results 22 including 12 from 14 complex 13 a 14 complex 14 complex 15 interplay 14 complex 21 factors 15 interplay 16 between 15 interplay 21 factors 16 between 19 and 17 stressful 18 events 18 events 19 and 19 and 20 vulnerability 22 including 24 deficits 23 cognitive 24 deficits the aim of this systematic literature review was to identify the neurocognitive markers associated with suicide vulnerability in elderly people . 0 ###LEFT-WALL### 2 aim 0 ###LEFT-WALL### 14 associated 0 ###LEFT-WALL### 21 . 1 the 2 aim 2 aim 3 of 2 aim 14 associated 3 of 6 literature 4 this 5 systematic 5 systematic 6 literature 6 literature 7 review 6 literature 10 identify 7 review 8 was 8 was 9 to 8 was 10 identify 9 to 10 identify 10 identify 13 markers 11 the 13 markers 12 neurocognitive 13 markers 14 associated 15 with 14 associated 18 in 15 with 17 vulnerability 16 suicide 17 vulnerability 18 in 20 people 19 elderly 20 people method : a systematic english medline literature search of cohort studies , [case] - control studies and cross - sectional studies published between january 1960 and december 2012 was performed , combining the mesh terms " suicide " , " neuropsychology " , " neuropsychological tests " , " executive function " , " magnetic resonance imaging " , " diffusion magnetic resonance imaging " , " positron - emission tomography " , " prefrontal cortex " , " tomography , emission - computed , single - photon " , and " diffusion tensor imaging " . 0 ###LEFT-WALL### 1 method 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 12 , 1 method 2 : 2 : 8 search 3 a 8 search 4 systematic 8 search 5 english 8 search 6 medline 8 search 7 literature 8 search 8 search 9 of 9 of 11 studies 10 cohort 11 studies 12 , 14 - 12 , 19 - 14 - 17 and 15 control 16 studies 16 studies 17 and 17 and 18 cross 17 and 19 - 19 - 26 and 19 - 31 , 20 sectional 21 studies 21 studies 22 published 21 studies 26 and 22 published 23 between 23 between 24 january 24 january 25 1960 26 and 27 december 26 and 28 2012 26 and 29 was 26 and 30 performed 28 2012 29 was 31 , 32 combining 31 , 43 , 32 combining 34 mesh 32 combining 35 terms 33 the 34 mesh 35 terms 36 " 35 terms 37 suicide 37 suicide 38 " 37 suicide 41 neuropsychology 39 , 40 " 39 , 41 neuropsychology 41 neuropsychology 42 " 41 neuropsychology 43 , 43 , 44 " 43 , 46 tests 43 , 48 , 45 neuropsychological 46 tests 46 tests 47 " 48 , 49 " 48 , 51 function 48 , 53 , 50 executive 51 function 51 function 52 " 53 , 54 " 53 , 57 imaging 53 , 59 , 55 magnetic 56 resonance 56 resonance 57 imaging 57 imaging 58 " 59 , 60 " 59 , 64 imaging 59 , 66 , 61 diffusion 62 magnetic 62 magnetic 63 resonance 63 resonance 64 imaging 64 imaging 65 " 66 , 67 " 66 , 68 positron 66 , 69 - 69 - 71 tomography 69 - 73 , 70 emission 71 tomography 71 tomography 72 " 73 , 74 " 73 , 76 cortex 73 , 84 computed 73 , 85 , 75 prefrontal 76 cortex 76 cortex 77 " 76 cortex 80 tomography 76 cortex 84 computed 78 , 79 " 78 , 80 tomography 80 tomography 82 emission 80 tomography 83 - 81 , 82 emission 82 emission 83 - 85 , 91 and 86 single 88 photon 86 single 91 and 87 - 88 photon 88 photon 89 " 88 photon 90 , 91 and 92 " 91 and 95 imaging 91 and 97 . 93 diffusion 94 tensor 94 tensor 95 imaging 95 imaging 96 " the abstract selection was based on the strobe checklist for observational studies . 0 ###LEFT-WALL### 3 selection 0 ###LEFT-WALL### 5 based 0 ###LEFT-WALL### 13 . 1 the 3 selection 2 abstract 3 selection 3 selection 4 was 4 was 5 based 5 based 6 on 6 on 9 checklist 7 the 9 checklist 8 strobe 9 checklist 9 checklist 10 for 10 for 12 studies 11 observational 12 studies results : of the 446 original articles , 10 neuropsychological and 4 brain imaging studies were selected . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 8 , 0 ###LEFT-WALL### 18 . 1 results 2 : 2 : 3 of 3 of 7 articles 4 the 5 446 5 446 7 articles 6 original 7 articles 8 , 15 studies 8 , 17 selected 9 10 15 studies 10 neuropsychological 11 and 11 and 14 imaging 11 and 15 studies 12 4 14 imaging 13 brain 14 imaging 15 studies 16 were 16 were 17 selected the number of suicidal subjects ranged from 10 to 29 ( mean age=66.8 to 79.1 years old , 0 - 85 % women ) . 0 ###LEFT-WALL### 5 subjects 0 ###LEFT-WALL### 6 ranged 0 ###LEFT-WALL### 25 . 1 the 2 number 2 number 3 of 2 number 5 subjects 3 of 5 subjects 4 suicidal 5 subjects 5 subjects 6 ranged 6 ranged 7 from 7 from 9 to 8 10 9 to 9 to 10 29 9 to 13 age=66.8 11 ( 13 age=66.8 12 mean 13 age=66.8 13 age=66.8 14 to 13 age=66.8 17 old 13 age=66.8 23 women 13 age=66.8 24 ) 14 to 15 79.1 16 years 17 old 18 , 23 women 19 0 20 - 20 - 21 85 20 - 22 % 22 % 23 women 23 women 24 ) conclusion : this literature review confirms the existence of neurocognitive markers of suicide vulnerability in elderly people . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 5 review 2 : 6 confirms 2 : 18 . 3 this 5 review 4 literature 5 review 5 review 6 confirms 6 confirms 8 existence 6 confirms 15 in 7 the 8 existence 8 existence 9 of 9 of 11 markers 10 neurocognitive 11 markers 11 markers 12 of 12 of 14 vulnerability 13 suicide 14 vulnerability 15 in 17 people 16 elderly 17 people a neuropsychological assessment could thus help to identify the suicide vulnerability of a depressed elderly person , a first step for both pharmacological and psychotherapeutic cares . 0 ###LEFT-WALL### 3 assessment 0 ###LEFT-WALL### 6 help 1 a 3 assessment 2 neuropsychological 3 assessment 3 assessment 4 could 4 could 6 help 5 thus 6 help 6 help 7 to 6 help 8 identify 7 to 8 identify 8 identify 11 vulnerability 9 the 11 vulnerability 10 suicide 11 vulnerability 11 vulnerability 12 of 11 vulnerability 20 step 12 of 16 person 13 a 14 depressed 13 a 16 person 14 depressed 16 person 15 elderly 16 person 17 , 20 step 18 a 20 step 19 first 20 step 20 step 21 for 20 step 27 . 21 for 26 cares 22 both 26 cares 23 pharmacological 24 and 24 and 25 psychotherapeutic 24 and 26 cares self - rated health is a frequently used measure , notably in the field of gerontology . 0 ###LEFT-WALL### 4 health 0 ###LEFT-WALL### 5 is 1 self 2 - 1 self 4 health 3 rated 4 health 4 health 5 is 5 is 9 measure 6 a 9 measure 7 frequently 8 used 8 used 9 measure 9 measure 12 in 10 , 11 notably 10 , 12 in 12 in 14 field 12 in 17 . 13 the 14 field 14 field 15 of 15 of 16 gerontology different authors have studied factors that can influence self [-] rated health among older persons and , according to studies , the factors taken into account and their influence vary . 0 ###LEFT-WALL### 2 authors 0 ###LEFT-WALL### 4 studied 0 ###LEFT-WALL### 16 and 0 ###LEFT-WALL### 31 . 1 different 2 authors 2 authors 3 have 3 have 4 studied 4 studied 5 factors 4 studied 13 among 5 factors 6 that 5 factors 7 can 6 that 7 can 7 can 8 influence 8 influence 12 health 9 self 11 rated 11 rated 12 health 13 among 15 persons 14 older 15 persons 16 and 17 , 16 and 27 and 16 and 30 vary 17 , 19 to 18 according 19 to 19 to 20 studies 19 to 21 , 19 to 27 and 22 the 23 factors 23 factors 24 taken 23 factors 27 and 24 taken 26 account 25 into 26 account 27 and 29 influence 27 and 30 vary 28 their 29 influence this article aims at synthesising the biomedical literature , published since 1993 , on factors that influence self - rated health of [non] [-] institutionalised older persons aged 65 years [and] [over] , with a focus on cross - sectional quantitative studies . 0 ###LEFT-WALL### 2 article 0 ###LEFT-WALL### 3 aims 0 ###LEFT-WALL### 9 , 1 this 2 article 2 article 3 aims 3 aims 4 at 4 at 5 synthesising 5 synthesising 8 literature 6 the 8 literature 7 biomedical 8 literature 9 , 21 health 10 published 11 since 10 published 19 - 10 published 21 health 11 since 12 1993 12 1993 14 on 13 , 14 on 14 on 15 factors 14 on 19 - 15 factors 16 that 15 factors 17 influence 16 that 17 influence 17 influence 18 self 20 rated 21 health 21 health 22 of 21 health 28 aged 22 of 27 persons 25 institutionalised 27 persons 26 older 27 persons 28 aged 30 years 28 aged 34 with 29 65 30 years 33 , 34 with 34 with 36 focus 34 with 43 . 35 a 36 focus 36 focus 37 on 36 focus 42 studies 37 on 38 cross 39 - 42 studies 40 sectional 42 studies 41 quantitative 42 studies 42 studies 43 . of the 1801 articles that were identified by our search strategy in the medline database , 22 were retained . 0 ###LEFT-WALL### 17 22 0 ###LEFT-WALL### 19 retained 0 ###LEFT-WALL### 20 . 1 of 4 articles 1 of 16 , 1 of 17 22 2 the 3 1801 3 1801 4 articles 4 articles 5 that 4 articles 6 were 5 that 6 were 6 were 7 identified 7 identified 8 by 7 identified 12 in 8 by 11 strategy 9 our 11 strategy 10 search 11 strategy 12 in 15 database 13 the 15 database 14 medline 15 database 17 22 18 were 18 were 19 retained the proportion of older persons assessing their health positively ranged , depending on the studies , from 48.4 % to 78.0 % . 0 ###LEFT-WALL### 2 proportion 0 ###LEFT-WALL### 10 ranged 0 ###LEFT-WALL### 23 . 1 the 2 proportion 2 proportion 3 of 2 proportion 10 ranged 3 of 5 persons 4 older 5 persons 5 persons 6 assessing 6 assessing 8 health 7 their 8 health 9 positively 10 ranged 10 ranged 12 depending 10 ranged 17 from 10 ranged 20 to 11 , 12 depending 12 depending 13 on 12 depending 16 , 13 on 15 studies 14 the 15 studies 17 from 19 % 18 48.4 19 % 20 to 22 % 21 78.0 22 % fifteen studies out of 22 investigated what was rather associated with an unfavourable self - rated health . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 6 investigated 0 ###LEFT-WALL### 15 - 0 ###LEFT-WALL### 18 . 1 fifteen 2 studies 2 studies 4 of 2 studies 6 investigated 3 out 4 of 4 of 5 22 6 investigated 7 what 6 investigated 11 with 7 what 8 was 8 was 10 associated 9 rather 10 associated 11 with 14 self 12 an 13 unfavourable 12 an 14 self 13 unfavourable 14 self 15 - 17 health 16 rated 17 health two studies took into account only one kind of independent variables . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 3 took 0 ###LEFT-WALL### 12 . 1 two 2 studies 2 studies 3 took 3 took 5 account 3 took 11 variables 4 into 5 account 6 only 7 one 7 one 8 kind 8 kind 9 of 8 kind 11 variables 9 of 11 variables 10 independent 11 variables in more than half of the studies , 1 to several variables belonging to at least 3 kinds of independent variables were associated with self [-] rated health in multivariable analysis . 0 ###LEFT-WALL### 12 variables 0 ###LEFT-WALL### 23 associated 0 ###LEFT-WALL### 32 . 1 in 4 half 1 in 8 , 1 in 12 variables 2 more 3 than 3 than 4 half 4 half 5 of 5 of 7 studies 6 the 7 studies 9 1 10 to 10 to 11 several 10 to 12 variables 12 variables 13 belonging 12 variables 14 to 12 variables 19 of 12 variables 22 were 14 to 18 kinds 15 at 16 least 16 least 17 3 17 3 18 kinds 19 of 21 variables 20 independent 21 variables 22 were 23 associated 23 associated 24 with 23 associated 29 in 24 with 28 health 25 self 27 rated 27 rated 28 health 29 in 31 analysis 30 multivariable 31 analysis the associations between these different kinds of independent variables considered ( sociodemographic characteristics - morbidity - functional status - mental health - social support - other variables ) and self [-] rated health are here presented and synthesized . 0 ###LEFT-WALL### 29 and 0 ###LEFT-WALL### 34 are 0 ###LEFT-WALL### 39 . 1 the 2 associations 2 associations 3 between 2 associations 29 and 3 between 9 variables 4 these 6 kinds 5 different 6 kinds 6 kinds 7 of 6 kinds 9 variables 7 of 9 variables 8 independent 9 variables 9 variables 10 considered 9 variables 13 characteristics 9 variables 18 status 11 ( 13 characteristics 12 sociodemographic 13 characteristics 13 characteristics 15 morbidity 13 characteristics 16 - 14 - 15 morbidity 15 morbidity 16 - 16 - 18 status 17 functional 18 status 18 status 22 - 18 status 28 ) 19 - 22 - 20 mental 21 health 21 health 22 - 22 - 24 support 22 - 28 ) 23 social 24 support 24 support 27 variables 25 - 27 variables 26 other 27 variables 27 variables 28 ) 29 and 33 health 29 and 34 are 30 self 32 rated 32 rated 33 health 34 are 35 here 34 are 37 and 36 presented 37 and 37 and 38 synthesized this work shows that the factors that influence self [-] rated health among older people , factors measured differently according to authors , are varied and belong to different domains . 0 ###LEFT-WALL### 2 work 0 ###LEFT-WALL### 3 shows 0 ###LEFT-WALL### 31 . 1 this 2 work 2 work 3 shows 3 shows 4 that 4 that 6 factors 4 that 26 and 5 the 6 factors 6 factors 7 that 6 factors 8 influence 6 factors 17 factors 6 factors 24 are 7 that 8 influence 8 influence 12 health 9 self 11 rated 11 rated 12 health 12 health 13 among 13 among 15 people 14 older 15 people 16 , 17 factors 17 factors 18 measured 17 factors 23 , 18 measured 19 differently 18 measured 21 to 20 according 21 to 21 to 22 authors 24 are 26 and 25 varied 26 and 26 and 27 belong 27 belong 28 to 28 to 30 domains 29 different 30 domains these domains include morbidity , functional status , as well as sociodemographic characteristics , mental health , certain aspects of social support and other kinds of factors . 0 ###LEFT-WALL### 2 domains 0 ###LEFT-WALL### 3 include 0 ###LEFT-WALL### 28 . 1 these 2 domains 2 domains 3 include 3 include 4 morbidity 3 include 11 as 4 morbidity 7 status 5 , 7 status 6 functional 7 status 7 status 8 , 9 as 10 well 10 well 11 as 11 as 23 and 12 sociodemographic 13 characteristics 13 characteristics 14 , 14 , 16 health 14 , 17 , 15 mental 16 health 17 , 19 aspects 17 , 23 and 18 certain 19 aspects 19 aspects 20 of 20 of 22 support 21 social 22 support 23 and 25 kinds 23 and 26 of 24 other 25 kinds 26 of 27 factors cognitive decline in elderly people often derives from the interaction between aging - related changes and age - related diseases and covers a large spectrum of clinical manifestations , from intact cognition through mild cognitive impairment and dementia . 0 ###LEFT-WALL### 2 decline 1 cognitive 2 decline 2 decline 3 in 3 in 5 people 4 elderly 5 people 5 people 21 and 6 often 7 derives 7 derives 8 from 7 derives 11 between 7 derives 21 and 8 from 10 interaction 9 the 10 interaction 11 between 12 aging 12 aging 20 diseases 13 - 14 related 14 related 16 and 14 related 18 - 14 related 19 related 15 changes 16 and 16 and 17 age 19 related 20 diseases 21 and 22 covers 21 and 25 spectrum 21 and 30 from 23 a 24 large 23 a 25 spectrum 24 large 25 spectrum 25 spectrum 26 of 26 of 28 manifestations 27 clinical 28 manifestations 29 , 30 from 30 from 32 cognition 30 from 39 . 31 intact 32 cognition 32 cognition 33 through 33 through 37 and 34 mild 36 impairment 35 cognitive 36 impairment 36 impairment 37 and 37 and 38 dementia epidemiological evidence supports the hypothesis that modifiable lifestyle - related factors are associated with cognitive decline [,] opening new avenues for prevention . 0 ###LEFT-WALL### 2 evidence 0 ###LEFT-WALL### 3 supports 0 ###LEFT-WALL### 9 - 1 epidemiological 2 evidence 2 evidence 3 supports 3 supports 8 lifestyle 4 the 8 lifestyle 5 hypothesis 8 lifestyle 6 that 7 modifiable 7 modifiable 8 lifestyle 9 - 11 factors 9 - 13 associated 9 - 23 . 10 related 11 factors 11 factors 12 are 12 are 13 associated 13 associated 14 with 14 with 20 avenues 15 cognitive 16 decline 16 decline 18 opening 18 opening 20 avenues 19 new 20 avenues 20 avenues 21 for 21 for 22 prevention diet in particular has become the object of intense research in relation to cognitive aging and neurodegenerative disease . 0 ###LEFT-WALL### 1 diet 0 ###LEFT-WALL### 5 become 0 ###LEFT-WALL### 19 . 1 diet 3 particular 1 diet 4 has 2 in 3 particular 4 has 5 become 5 become 7 object 5 become 13 to 6 the 7 object 7 object 8 of 8 of 10 research 9 intense 10 research 11 in 12 relation 12 relation 13 to 13 to 16 and 14 cognitive 15 aging 14 cognitive 16 and 16 and 18 disease 17 neurodegenerative 18 disease we reviewed the most recent findings in this rapidly expanding field . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 reviewed 0 ###LEFT-WALL### 12 . 1 we 2 reviewed 2 reviewed 6 findings 2 reviewed 7 in 3 the 4 most 4 most 6 findings 5 recent 6 findings 7 in 11 field 8 this 11 field 9 rapidly 10 expanding 10 expanding 11 field some nutrients , such as vitamins and fatty acids , have been studied longer than others , but strong scientific evidence of an association is lacking even for these compounds . 0 ###LEFT-WALL### 2 nutrients 0 ###LEFT-WALL### 13 studied 0 ###LEFT-WALL### 18 but 0 ###LEFT-WALL### 31 . 1 some 2 nutrients 2 nutrients 5 as 2 nutrients 11 have 3 , 5 as 4 such 5 as 5 as 7 and 5 as 10 , 6 vitamins 7 and 7 and 9 acids 8 fatty 9 acids 11 have 12 been 12 been 13 studied 13 studied 14 longer 13 studied 15 than 15 than 16 others 17 , 18 but 18 but 21 evidence 18 but 25 is 19 strong 21 evidence 20 scientific 21 evidence 21 evidence 22 of 21 evidence 25 is 22 of 24 association 23 an 24 association 25 is 26 lacking 26 lacking 27 even 27 even 28 for 28 for 30 compounds 29 these 30 compounds specific dietary patterns , like the mediterranean diet , may be more beneficial than [a] high consumption of single nutrients or specific food items . 0 ###LEFT-WALL### 3 patterns 0 ###LEFT-WALL### 11 be 0 ###LEFT-WALL### 25 . 1 specific 3 patterns 2 dietary 3 patterns 3 patterns 5 like 3 patterns 10 may 4 , 5 like 5 like 8 diet 5 like 9 , 6 the 8 diet 7 mediterranean 8 diet 10 may 11 be 11 be 24 items 12 more 24 items 13 beneficial 14 than 13 beneficial 21 or 14 than 17 consumption 14 than 18 of 16 high 17 consumption 18 of 20 nutrients 19 single 20 nutrients 21 or 22 specific 21 or 23 food 23 food 24 items a strong link between vascular risk factors and dementia has been shown , and the association of [diet] with several vascular and metabolic diseases is well known . 0 ###LEFT-WALL### 3 link 0 ###LEFT-WALL### 12 shown 0 ###LEFT-WALL### 14 and 0 ###LEFT-WALL### 28 . 1 a 2 strong 1 a 3 link 2 strong 3 link 3 link 4 between 3 link 10 has 4 between 8 and 5 vascular 7 factors 6 risk 7 factors 7 factors 8 and 8 and 9 dementia 10 has 11 been 11 been 12 shown 13 , 14 and 14 and 16 association 14 and 25 is 15 the 16 association 16 association 17 of 16 association 25 is 17 of 19 with 19 with 24 diseases 20 several 24 diseases 21 vascular 22 and 22 and 23 metabolic 22 and 24 diseases 25 is 26 well 25 is 27 known other plausible mechanisms underlying the relationship [between] diet and cognitive decline , such as inflammation and oxidative stress , have been established . 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 22 established 0 ###LEFT-WALL### 23 . 1 other 3 mechanisms 2 plausible 3 mechanisms 3 mechanisms 4 underlying 3 mechanisms 9 and 4 underlying 8 diet 5 the 8 diet 6 relationship 8 diet 9 and 11 decline 9 and 14 as 9 and 20 have 10 cognitive 11 decline 12 , 14 as 13 such 14 as 14 as 16 and 14 as 19 , 15 inflammation 16 and 16 and 18 stress 17 oxidative 18 stress 20 have 21 been 21 been 22 established in addition to the traditional etiological pathways , new hypotheses , such as the role of the intestinal microbiome [in] cognitive function , have been suggested and warrant further investigation . 0 ###LEFT-WALL### 10 hypotheses 0 ###LEFT-WALL### 27 and 0 ###LEFT-WALL### 31 . 1 in 2 addition 1 in 8 , 1 in 10 hypotheses 2 addition 3 to 3 to 7 pathways 4 the 7 pathways 5 traditional 7 pathways 6 etiological 7 pathways 9 new 10 hypotheses 10 hypotheses 13 as 10 hypotheses 24 have 11 , 13 as 12 such 13 as 13 as 15 role 13 as 23 , 14 the 15 role 15 role 16 of 16 of 22 function 17 the 22 function 18 intestinal 22 function 19 microbiome 22 function 21 cognitive 22 function 24 have 25 been 25 been 27 and 26 suggested 27 and 27 and 28 warrant 28 warrant 30 investigation 29 further 30 investigation haemoglobins are iron - containing proteins that transport oxygen in the blood of most vertebrates . 0 ###LEFT-WALL### 1 haemoglobins 0 ###LEFT-WALL### 3 iron 1 haemoglobins 2 are 2 are 3 iron 3 iron 5 containing 4 - 5 containing 5 containing 6 proteins 5 containing 16 . 6 proteins 7 that 6 proteins 8 transport 7 that 8 transport 8 transport 9 oxygen 8 transport 10 in 10 in 12 blood 11 the 12 blood 12 blood 13 of 13 of 15 vertebrates 14 most 15 vertebrates the mitochondrion is the cellular organelle which consumes oxygen in order to synthesise atp . 0 ###LEFT-WALL### 2 mitochondrion 0 ###LEFT-WALL### 3 is 0 ###LEFT-WALL### 15 . 1 the 2 mitochondrion 2 mitochondrion 3 is 3 is 6 organelle 4 the 6 organelle 5 cellular 6 organelle 6 organelle 7 which 6 organelle 8 consumes 7 which 8 consumes 8 consumes 9 oxygen 8 consumes 10 in 10 in 11 order 11 order 12 to 11 order 13 synthesise 12 to 13 synthesise 13 synthesise 14 atp mitochondrial dysfunction is implicated in neurodegeneration and ageing . 0 ###LEFT-WALL### 2 dysfunction 0 ###LEFT-WALL### 4 implicated 0 ###LEFT-WALL### 9 . 1 mitochondrial 2 dysfunction 2 dysfunction 3 is 3 is 4 implicated 4 implicated 5 in 5 in 7 and 6 neurodegeneration 7 and 7 and 8 ageing we find that α and β haemoglobin ( hba and hbb ) proteins are altered in their distribution in mitochondrial fractions from degenerating brain . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 find 0 ###LEFT-WALL### 25 . 1 we 2 find 2 find 3 that 3 that 13 proteins 3 that 15 altered 4 α 5 and 5 and 7 haemoglobin 5 and 10 and 5 and 13 proteins 6 β 7 haemoglobin 8 ( 10 and 9 hba 10 and 10 and 11 hbb 10 and 12 ) 13 proteins 14 are 14 are 15 altered 15 altered 16 in 15 altered 19 in 16 in 18 distribution 17 their 18 distribution 19 in 21 fractions 20 mitochondrial 21 fractions 21 fractions 22 from 22 from 24 brain 23 degenerating 24 brain we demonstrate that both hba and hbb are co - localised with the mitochondrion in mammalian brain . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 demonstrate 1 we 2 demonstrate 2 demonstrate 3 that 3 that 6 and 3 that 8 are 4 both 6 and 5 hba 6 and 6 and 7 hbb 6 and 8 are 8 are 9 co 9 co 11 localised 10 - 11 localised 11 localised 12 with 11 localised 15 in 11 localised 18 . 12 with 14 mitochondrion 13 the 14 mitochondrion 15 in 17 brain 16 mammalian 17 brain the precise localisation of the hbs is within the inner membrane space and associated with inner mitochondrial membrane . 0 ###LEFT-WALL### 3 localisation 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 19 . 1 the 3 localisation 2 precise 3 localisation 3 localisation 4 of 3 localisation 13 and 4 of 6 hbs 5 the 6 hbs 7 is 8 within 7 is 13 and 8 within 12 space 9 the 12 space 10 inner 11 membrane 11 membrane 12 space 13 and 14 associated 13 and 15 with 15 with 18 membrane 16 inner 18 membrane 17 mitochondrial 18 membrane relative mitochondrial to cytoplasmic ratios of hba and hbb show changing distributions of these proteins during the process of neurodegeneration in the pcd ( 5j ) mouse brain . 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 10 show 0 ###LEFT-WALL### 29 . 1 relative 2 mitochondrial 1 relative 8 and 2 mitochondrial 3 to 3 to 5 ratios 4 cytoplasmic 5 ratios 5 ratios 6 of 6 of 7 hba 8 and 9 hbb 8 and 10 show 10 show 12 distributions 10 show 16 during 10 show 21 in 11 changing 12 distributions 12 distributions 13 of 13 of 15 proteins 14 these 15 proteins 16 during 18 process 17 the 18 process 18 process 19 of 19 of 20 neurodegeneration 21 in 28 brain 22 the 28 brain 23 pcd 25 5j 23 pcd 27 mouse 24 ( 25 5j 25 5j 26 ) 27 mouse 28 brain a significant difference in mitochondrial hba and hbb content in the mitochondrial fraction is seen at 31 days after birth , this corresponds to a stage when dynamic neuronal loss is measured to be [greatest] in the purkinje cell degeneration mouse . 0 ###LEFT-WALL### 3 difference 0 ###LEFT-WALL### 15 seen 0 ###LEFT-WALL### 42 . 1 a 3 difference 2 significant 3 difference 3 difference 4 in 3 difference 9 content 3 difference 14 is 4 in 7 and 5 mitochondrial 6 hba 6 hba 7 and 7 and 8 hbb 9 content 10 in 10 in 13 fraction 11 the 13 fraction 12 mitochondrial 13 fraction 14 is 15 seen 15 seen 16 at 15 seen 27 when 16 at 18 days 17 31 18 days 18 days 22 this 18 days 23 corresponds 19 after 20 birth 19 after 21 , 19 after 22 this 22 this 23 corresponds 23 corresponds 24 to 24 to 26 stage 25 a 26 stage 27 when 30 loss 27 when 34 be 28 dynamic 30 loss 29 neuronal 30 loss 30 loss 31 is 31 is 32 measured 32 measured 33 to 33 to 34 be 34 be 36 in 36 in 41 mouse 37 the 41 mouse 38 purkinje 39 cell 39 cell 41 mouse 40 degeneration 41 mouse we also report changes in mitochondrial hba and hbb levels in ageing brain and muscle . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 report 0 ###LEFT-WALL### 16 . 1 we 3 report 2 also 3 report 3 report 4 changes 3 report 5 in 3 report 11 in 5 in 10 levels 6 mitochondrial 10 levels 7 hba 8 and 8 and 9 hbb 9 hbb 10 levels 11 in 14 and 12 ageing 13 brain 13 brain 14 and 14 and 15 muscle significant differences in mitochondrial hba and hbb can be seen when comparing aged brain to muscle , suggesting tissue specific functions of these proteins in the mitochondrion . 0 ###LEFT-WALL### 2 differences 0 ###LEFT-WALL### 10 seen 1 significant 2 differences 2 differences 3 in 2 differences 8 can 3 in 6 and 4 mitochondrial 5 hba 5 hba 6 and 6 and 7 hbb 8 can 9 be 9 be 10 seen 10 seen 11 when 10 seen 15 to 11 when 12 comparing 12 comparing 14 brain 13 aged 14 brain 15 to 16 muscle 16 muscle 18 suggesting 17 , 18 suggesting 18 suggesting 21 functions 18 suggesting 25 in 18 suggesting 28 . 19 tissue 21 functions 20 specific 21 functions 21 functions 22 of 22 of 24 proteins 23 these 24 proteins 25 in 27 mitochondrion 26 the 27 mitochondrion in muscle there are significant differences between hba levels in old and young mitochondria . 0 ###LEFT-WALL### 1 in 0 ###LEFT-WALL### 4 are 0 ###LEFT-WALL### 15 . 1 in 2 muscle 1 in 4 are 2 muscle 3 there 4 are 6 differences 5 significant 6 differences 6 differences 7 between 7 between 9 levels 8 hba 9 levels 9 levels 10 in 10 in 14 mitochondria 11 old 12 and 12 and 13 young 12 and 14 mitochondria to understand whether the changes detected in mitochondrial hbs are of clinical significance , we examined parkinson 's disease brain , immunohistochemistry studies suggest that cell bodies in the substantia nigra accumulate mitochondrial hb . 0 ###LEFT-WALL### 15 we 0 ###LEFT-WALL### 16 examined 0 ###LEFT-WALL### 21 , 0 ###LEFT-WALL### 35 . 1 to 2 understand 1 to 14 , 1 to 15 we 2 understand 3 whether 3 whether 5 changes 3 whether 10 are 4 the 5 changes 5 changes 6 detected 5 changes 10 are 6 detected 7 in 7 in 9 hbs 8 mitochondrial 9 hbs 10 are 11 of 11 of 13 significance 12 clinical 13 significance 15 we 16 examined 16 examined 20 brain 17 parkinson 18 's 18 's 20 brain 19 disease 20 brain 21 , 23 studies 21 , 24 suggest 22 immunohistochemistry 23 studies 23 studies 24 suggest 24 suggest 25 that 25 that 27 bodies 25 that 32 accumulate 26 cell 27 bodies 27 bodies 28 in 27 bodies 32 accumulate 28 in 31 nigra 29 the 31 nigra 30 substantia 31 nigra 32 accumulate 34 hb 33 mitochondrial 34 hb however , western blotting of mitochondrial fractions from pd and control brains indicates significantly less hb in pd brain mitochondria . 0 ###LEFT-WALL### 4 blotting 0 ###LEFT-WALL### 13 indicates 0 ###LEFT-WALL### 21 . 1 however 2 , 1 however 4 blotting 3 western 4 blotting 4 blotting 5 of 4 blotting 13 indicates 5 of 10 and 6 mitochondrial 7 fractions 7 fractions 8 from 7 fractions 10 and 8 from 9 pd 10 and 12 brains 11 control 12 brains 13 indicates 20 mitochondria 14 significantly 15 less 15 less 20 mitochondria 16 hb 17 in 16 hb 20 mitochondria 17 in 18 pd 19 brain 20 mitochondria one explanation could be a specific loss of cells containing mitochondria loaded with hb proteins . 0 ###LEFT-WALL### 2 explanation 0 ###LEFT-WALL### 4 be 0 ###LEFT-WALL### 16 . 1 one 2 explanation 2 explanation 3 could 3 could 4 be 4 be 7 loss 5 a 6 specific 5 a 7 loss 6 specific 7 loss 7 loss 8 of 7 loss 10 containing 7 loss 12 loaded 8 of 9 cells 10 containing 11 mitochondria 12 loaded 13 with 13 with 15 proteins 14 hb 15 proteins our study opens the door to an examination of the role of hb [function] , within the context of the mitochondrion - in health and disease . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 opens 0 ###LEFT-WALL### 27 . 1 our 2 study 2 study 3 opens 3 opens 5 door 3 opens 6 to 3 opens 23 in 4 the 5 door 6 to 8 examination 7 an 8 examination 8 examination 9 of 9 of 11 role 10 the 11 role 11 role 12 of 12 of 13 hb 13 hb 16 within 15 , 16 within 16 within 18 context 16 within 22 - 17 the 18 context 18 context 19 of 19 of 21 mitochondrion 20 the 21 mitochondrion 23 in 25 and 24 health 25 and 25 and 26 disease endothelin - 1 ( et - 1 ) is a short chained peptide [primarily] of endothelial origin . 0 ###LEFT-WALL### 1 endothelin 0 ###LEFT-WALL### 9 is 0 ###LEFT-WALL### 18 . 1 endothelin 3 1 1 endothelin 7 1 1 endothelin 9 is 2 - 3 1 3 1 5 et 3 1 6 - 4 ( 5 et 5 et 6 - 6 - 7 1 7 1 8 ) 9 is 13 peptide 10 a 11 short 10 a 13 peptide 11 short 13 peptide 12 chained 13 peptide 13 peptide 15 of 15 of 17 origin 16 endothelial 17 origin concentrations of this peptide are increased in subjects [with] [hypertension] , primary pulmonary hypertension and myocardial infarction , however its short [half] - life makes quantification [difficult] . 0 ###LEFT-WALL### 1 concentrations 0 ###LEFT-WALL### 6 increased 0 ###LEFT-WALL### 28 . 1 concentrations 2 of 1 concentrations 5 are 2 of 4 peptide 3 this 4 peptide 5 are 6 increased 6 increased 7 in 6 increased 19 however 7 in 15 and 8 subjects 11 , 11 , 14 hypertension 11 , 15 and 12 primary 14 hypertension 13 pulmonary 14 hypertension 15 and 17 infarction 15 and 18 , 16 myocardial 17 infarction 19 however 24 life 19 however 25 makes 20 its 24 life 21 short 23 - 21 short 24 life 24 life 25 makes 25 makes 26 quantification the [c] [-] terminal of proet - 1 ( ctproet - 1 ) is stoichiometrically secreted with its bioactive peptide and would be a valid method of measuring the active peptide as it has a stable [half] - life and [is] less resistant [to] proteolytic cleavage . 0 ###LEFT-WALL### 4 terminal 0 ###LEFT-WALL### 34 has 1 the 4 terminal 4 terminal 5 of 4 terminal 34 has 5 of 6 proet 6 proet 8 1 6 proet 21 and 7 - 8 1 8 1 11 - 8 1 21 and 9 ( 11 - 10 ctproet 11 - 11 - 12 1 11 - 13 ) 14 is 16 secreted 14 is 21 and 15 stoichiometrically 16 secreted 16 secreted 17 with 17 with 20 peptide 18 its 20 peptide 19 bioactive 20 peptide 21 and 22 would 22 would 23 be 23 be 26 method 23 be 32 as 24 a 26 method 25 valid 26 method 26 method 27 of 27 of 28 measuring 28 measuring 31 peptide 29 the 31 peptide 30 active 31 peptide 32 as 33 it 34 has 36 stable 35 a 36 stable 36 stable 40 and 38 - 40 and 39 life 40 and 40 and 46 cleavage 40 and 47 . 42 less 43 resistant 43 resistant 46 cleavage 45 proteolytic 46 cleavage the objective of this study was to understand the factors ( clinical , echocardiographic and biochemical ) that specifically influence plasma ctproet - 1 in healthy subjects . 0 ###LEFT-WALL### 2 objective 0 ###LEFT-WALL### 28 . 1 the 2 objective 2 objective 3 of 2 objective 6 was 3 of 5 study 4 this 5 study 6 was 7 to 6 was 8 understand 7 to 8 understand 8 understand 10 factors 8 understand 20 influence 9 the 10 factors 10 factors 15 and 10 factors 20 influence 11 ( 15 and 12 clinical 13 , 13 , 14 echocardiographic 13 , 15 and 15 and 16 biochemical 15 and 17 ) 18 that 19 specifically 19 specifically 20 influence 20 influence 27 subjects 21 plasma 27 subjects 22 ctproet 27 subjects 23 - 24 1 24 1 25 in 25 in 27 subjects 26 healthy 27 subjects plasma ctproet - 1 concentrations were quantified using a novel immunoluminometric sandwich assay . 0 ###LEFT-WALL### 2 ctproet 0 ###LEFT-WALL### 3 - 1 plasma 2 ctproet 3 - 5 concentrations 3 - 7 quantified 3 - 14 . 4 1 5 concentrations 5 concentrations 6 were 6 were 7 quantified 7 quantified 8 using 8 using 13 assay 9 a 10 novel 9 a 13 assay 10 novel 12 sandwich 11 immunoluminometric 12 sandwich 12 sandwich 13 assay in multivariate analyses , age ( p<0.001 ) , diastolic bp ( p=0.007 ) , la [size] ( p=0.001 ) and egfr ( p<0.001 ) were independently predictive [of] plasma ctproet - 1 levels in the healthy subjects . 0 ###LEFT-WALL### 21 and 0 ###LEFT-WALL### 26 were 1 in 3 analyses 1 in 21 and 2 multivariate 3 analyses 3 analyses 5 age 3 analyses 11 bp 4 , 5 age 5 age 7 p<0.001 5 age 9 , 6 ( 7 p<0.001 7 p<0.001 8 ) 9 , 11 bp 10 diastolic 11 bp 11 bp 13 p=0.007 11 bp 15 , 12 ( 13 p=0.007 13 p=0.007 14 ) 16 la 19 p=0.001 16 la 21 and 18 ( 19 p=0.001 19 p=0.001 20 ) 21 and 22 egfr 21 and 24 p<0.001 21 and 26 were 23 ( 24 p<0.001 24 p<0.001 25 ) 26 were 31 ctproet 27 independently 28 predictive 28 predictive 30 plasma 30 plasma 31 ctproet 31 ctproet 34 levels 32 - 34 levels 33 1 34 levels 34 levels 35 in 34 levels 39 . 35 in 38 subjects 36 the 38 subjects 37 healthy 38 subjects therefore the interpretation of plasma ctproet - 1 levels in such individuals should take into account these variables to avoid potential confounding . 0 ###LEFT-WALL### 3 interpretation 0 ###LEFT-WALL### 14 take 0 ###LEFT-WALL### 23 . 1 therefore 3 interpretation 2 the 3 interpretation 3 interpretation 4 of 3 interpretation 13 should 4 of 6 ctproet 5 plasma 6 ctproet 6 ctproet 8 1 6 ctproet 9 levels 7 - 8 1 8 1 9 levels 9 levels 10 in 10 in 12 individuals 11 such 12 individuals 13 should 14 take 14 take 16 account 14 take 18 variables 15 into 16 account 17 these 18 variables 18 variables 19 to 18 variables 22 confounding 19 to 20 avoid 20 avoid 21 potential 21 potential 22 confounding objectives : to better inform patients and physicians of the expected risk of adverse events and to assist hospitals ' efforts to improve the outcomes of patients undergoing implantable cardioverter - defibrillator [(] icd ) implantation , we developed and validated a risk model using data from the ncdr ( national cardiovascular data registry [ )(icd registry . 0 ###LEFT-WALL### 1 objectives 0 ###LEFT-WALL### 5 inform 0 ###LEFT-WALL### 16 and 1 objectives 2 : 2 : 3 to 3 to 5 inform 4 better 5 inform 5 inform 7 and 5 inform 13 of 6 patients 7 and 7 and 8 physicians 8 physicians 9 of 9 of 12 risk 10 the 12 risk 11 expected 12 risk 13 of 15 events 14 adverse 15 events 16 and 38 we 16 and 40 and 17 to 18 assist 17 to 37 , 17 to 38 we 18 assist 21 efforts 18 assist 22 to 19 hospitals 20 ' 20 ' 21 efforts 22 to 23 improve 23 improve 25 outcomes 24 the 25 outcomes 25 outcomes 26 of 25 outcomes 28 undergoing 26 of 27 patients 28 undergoing 36 implantation 29 implantable 36 implantation 30 cardioverter 34 icd 30 cardioverter 35 ) 30 cardioverter 36 implantation 31 - 34 icd 32 defibrillator 34 icd 34 icd 35 ) 38 we 40 and 39 developed 40 and 40 and 41 validated 41 validated 44 model 41 validated 45 using 41 validated 47 from 42 a 44 model 43 risk 44 model 45 using 46 data 47 from 49 ncdr 48 the 49 ncdr 49 ncdr 57 registry 50 ( 57 registry 51 national 52 cardiovascular 52 cardiovascular 53 data 53 data 54 registry 54 registry 56 )(icd 56 )(icd 57 registry 57 registry 58 . background : icd prolong life in selected patients , but icd implantation carries the risk of periprocedural complications . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 3 icd 2 : 4 prolong 2 : 10 but 2 : 19 . 3 icd 4 prolong 4 prolong 5 life 4 prolong 6 in 6 in 8 patients 7 selected 8 patients 9 , 10 but 10 but 12 implantation 10 but 13 carries 11 icd 12 implantation 12 implantation 13 carries 13 carries 15 risk 14 the 15 risk 15 risk 16 of 16 of 18 complications 17 periprocedural 18 complications methods : we analyzed data from 240,632 icd implantation procedures between april 1 , 2010 , and december [31] , 2011 in the registry . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 3 we 2 : 4 analyzed 3 we 4 analyzed 4 analyzed 5 data 4 analyzed 6 from 6 from 17 and 7 240,632 10 procedures 8 icd 10 procedures 9 implantation 10 procedures 10 procedures 11 between 10 procedures 17 and 11 between 12 april 12 april 13 1 12 april 15 2010 14 , 15 2010 15 2010 16 , 16 , 17 and 17 and 18 december 17 and 21 2011 20 , 21 2011 21 2011 22 in 21 2011 25 . 22 in 24 registry 23 the 24 registry the study group [was] divided into a derivation ( 70 % ) and a validation ( 30 % ) cohort . 0 ###LEFT-WALL### 20 cohort 0 ###LEFT-WALL### 21 . 1 the 3 group 2 study 3 group 3 group 5 divided 3 group 13 and 5 divided 6 into 6 into 8 derivation 7 a 8 derivation 8 derivation 11 % 9 ( 11 % 10 70 11 % 11 % 12 ) 13 and 15 validation 13 and 18 % 13 and 20 cohort 14 a 15 validation 16 ( 18 % 17 30 18 % 18 % 19 ) multivariable logistic regression was used to identify factors associated [with] in [-] hospital adverse events ( complications or mortality ) . 0 ###LEFT-WALL### 3 regression 0 ###LEFT-WALL### 5 used 0 ###LEFT-WALL### 21 . 1 multivariable 3 regression 2 logistic 3 regression 3 regression 4 was 4 was 5 used 5 used 6 to 5 used 7 identify 6 to 7 identify 7 identify 8 factors 8 factors 9 associated 9 associated 11 in 11 in 15 events 13 hospital 15 events 14 adverse 15 events 15 events 18 or 16 ( 18 or 17 complications 18 or 18 or 19 mortality 18 or 20 ) a parsimonious risk score was developed on the basis of beta estimates derived from the logistic model . 0 ###LEFT-WALL### 4 score 0 ###LEFT-WALL### 6 developed 0 ###LEFT-WALL### 18 . 1 a 2 parsimonious 1 a 4 score 2 parsimonious 4 score 3 risk 4 score 4 score 5 was 5 was 6 developed 6 developed 7 on 7 on 9 basis 8 the 9 basis 9 basis 10 of 10 of 12 estimates 11 beta 12 estimates 12 estimates 13 derived 13 derived 14 from 14 from 17 model 15 the 17 model 16 logistic 17 model hierarchical models were then used to calculate risk - standardized complication rates to account for differences in case mix [and] procedural volume . 0 ###LEFT-WALL### 2 models 0 ###LEFT-WALL### 5 used 0 ###LEFT-WALL### 9 - 1 hierarchical 2 models 2 models 3 were 3 were 4 then 3 were 5 used 5 used 6 to 5 used 7 calculate 6 to 7 calculate 7 calculate 8 risk 9 - 12 rates 9 - 18 case 9 - 23 . 10 standardized 11 complication 11 complication 12 rates 12 rates 13 to 12 rates 17 in 12 rates 18 case 13 to 14 account 14 account 15 for 14 account 17 in 15 for 16 differences 18 case 22 volume 19 mix 22 volume 21 procedural 22 volume results : overall , 4,388 patients ( 1.8 % ) experienced at least 1 in - hospital complication [or] death . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 4 , 1 results 2 : 2 : 3 overall 4 , 6 patients 4 , 11 experienced 4 , 16 - 5 4,388 6 patients 6 patients 9 % 6 patients 11 experienced 7 ( 9 % 8 1.8 9 % 9 % 10 ) 11 experienced 15 in 12 at 13 least 13 least 14 1 14 1 15 in 16 - 20 death 16 - 21 . 17 hospital 20 death 18 complication 20 death thirteen factors were independently associated with an increased risk of adverse outcomes . 0 ###LEFT-WALL### 2 factors 0 ###LEFT-WALL### 5 associated 0 ###LEFT-WALL### 13 . 1 thirteen 2 factors 2 factors 3 were 3 were 5 associated 4 independently 5 associated 5 associated 6 with 6 with 9 risk 7 an 9 risk 8 increased 9 risk 9 risk 10 of 10 of 12 outcomes 11 adverse 12 outcomes model performance was similar in the derivation and validation cohorts ( c - statistics = 0.724 and 0.719 , respectively ) . 0 ###LEFT-WALL### 2 performance 0 ###LEFT-WALL### 3 was 0 ###LEFT-WALL### 22 . 1 model 2 performance 2 performance 3 was 3 was 4 similar 4 similar 5 in 4 similar 20 respectively 5 in 8 and 6 the 7 derivation 7 derivation 8 and 8 and 10 cohorts 8 and 13 - 9 validation 10 cohorts 11 ( 13 - 12 c 13 - 13 - 14 statistics 13 - 19 , 14 statistics 17 and 15 = 16 0.724 16 0.724 17 and 17 and 18 0.719 19 , 20 respectively 20 respectively 21 ) the risk score characterized patients into low - and [-] high risk subgroups for adverse events ( ≤10 points , 0.3 % ; ≥30 points , 4.2 % ) . 0 ###LEFT-WALL### 5 patients 0 ###LEFT-WALL### 12 risk 0 ###LEFT-WALL### 23 ; 0 ###LEFT-WALL### 24 ≥30 0 ###LEFT-WALL### 30 . 1 the 5 patients 2 risk 4 characterized 3 score 4 characterized 4 characterized 5 patients 5 patients 6 into 5 patients 12 risk 6 into 9 and 7 low 9 and 8 - 9 and 9 and 11 high 12 risk 13 subgroups 13 subgroups 14 for 13 subgroups 22 % 14 for 16 events 15 adverse 16 events 16 events 19 points 17 ( 19 points 18 ≤10 19 points 19 points 20 , 20 , 22 % 21 0.3 22 % 22 % 23 ; 23 ; 24 ≥30 24 ≥30 25 points 25 points 28 % 26 , 28 % 27 4.2 28 % 28 % 29 ) the risk [-] standardized complication rates varied significantly across hospitals ( median [:] 1.77 , interquartile range 1.54 , 2.14 , 5th/95th percentiles : 1.16/3.15 [ )( 0 ###LEFT-WALL### 2 risk 0 ###LEFT-WALL### 4 standardized 0 ###LEFT-WALL### 21 , 0 ###LEFT-WALL### 27 )( 1 the 2 risk 2 risk 4 standardized 4 standardized 6 rates 4 standardized 8 significantly 4 standardized 9 across 5 complication 6 rates 6 rates 7 varied 9 across 10 hospitals 10 hospitals 12 median 10 hospitals 17 range 11 ( 12 median 12 median 14 1.77 12 median 15 , 15 , 17 range 16 interquartile 17 range 17 range 18 1.54 17 range 20 2.14 17 range 21 , 19 , 20 2.14 20 2.14 21 , 21 , 22 5th/95th 21 , 23 percentiles 21 , 24 : 22 5th/95th 23 percentiles 24 : 25 1.16/3.15 conclusions : we developed a simple model that predicts risk for in [-] hospital adverse events among patients undergoing icd placement . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 3 we 2 : 4 developed 2 : 22 . 3 we 4 developed 4 developed 7 model 4 developed 12 in 4 developed 17 among 5 a 6 simple 5 a 7 model 6 simple 7 model 7 model 8 that 7 model 11 for 8 that 9 predicts 9 predicts 10 risk 9 predicts 11 for 12 in 16 events 14 hospital 16 events 15 adverse 16 events 17 among 18 patients 18 patients 19 undergoing 19 undergoing 21 placement 20 icd 21 placement this can be used for shared decision making and to benchmark hospital performance . 0 ###LEFT-WALL### 1 this 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 14 . 1 this 2 can 2 can 9 and 3 be 4 used 3 be 9 and 4 used 5 for 5 for 8 making 6 shared 8 making 7 decision 8 making 9 and 10 to 9 and 11 benchmark 10 to 11 benchmark 11 benchmark 13 performance 12 hospital 13 performance ototoxicity is a major cause of the loss of hearing and balance in humans . 0 ###LEFT-WALL### 1 ototoxicity 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 15 . 1 ototoxicity 2 is 2 is 5 cause 3 a 5 cause 4 major 5 cause 5 cause 6 of 6 of 11 and 7 the 8 loss 8 loss 9 of 8 loss 11 and 9 of 10 hearing 11 and 12 balance 11 and 13 in 13 in 14 humans ototoxic compounds include pharmaceuticals such as aminoglycoside antibiotics , anti - malarial drugs , loop diuretics and chemotherapeutic platinum agents , and industrial chemicals including several solvents and nitriles . 0 ###LEFT-WALL### 1 ototoxic 0 ###LEFT-WALL### 2 compounds 0 ###LEFT-WALL### 9 , 0 ###LEFT-WALL### 30 . 1 ototoxic 2 compounds 2 compounds 4 pharmaceuticals 2 compounds 6 as 3 include 4 pharmaceuticals 5 such 6 as 6 as 8 antibiotics 7 aminoglycoside 8 antibiotics 9 , 13 drugs 9 , 14 , 10 anti 11 - 10 anti 13 drugs 12 malarial 13 drugs 14 , 15 loop 15 loop 22 and 16 diuretics 17 and 17 and 20 agents 17 and 21 , 17 and 22 and 18 chemotherapeutic 19 platinum 19 platinum 20 agents 22 and 24 chemicals 22 and 25 including 23 industrial 24 chemicals 25 including 28 and 26 several 27 solvents 27 solvents 28 and 28 and 29 nitriles human and rodent data indicate that the main target of toxicity is hair cells ( hcs ) , which are the mechanosensory cells responsible for sensory transduction in both the auditory and the vestibular system . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 5 indicate 0 ###LEFT-WALL### 18 , 0 ###LEFT-WALL### 36 . 1 human 2 and 2 and 4 data 2 and 5 indicate 3 rodent 4 data 5 indicate 6 that 6 that 9 target 6 that 12 is 7 the 9 target 8 main 9 target 9 target 10 of 9 target 12 is 10 of 11 toxicity 12 is 14 cells 13 hair 14 cells 14 cells 16 hcs 15 ( 16 hcs 16 hcs 17 ) 18 , 19 which 18 , 20 are 19 which 20 are 20 are 23 cells 21 the 23 cells 22 mechanosensory 23 cells 23 cells 24 responsible 24 responsible 25 for 24 responsible 28 in 25 for 27 transduction 26 sensory 27 transduction 28 in 32 and 29 both 32 and 30 the 31 auditory 31 auditory 32 and 32 and 35 system 33 the 35 system 34 vestibular 35 system nevertheless , the compounds may also affect the auditory and vestibular ganglion neurons . 0 ###LEFT-WALL### 4 compounds 0 ###LEFT-WALL### 7 affect 0 ###LEFT-WALL### 14 . 1 nevertheless 2 , 1 nevertheless 4 compounds 3 the 4 compounds 4 compounds 5 may 5 may 7 affect 6 also 7 affect 7 affect 13 neurons 8 the 13 neurons 9 auditory 10 and 10 and 11 vestibular 10 and 12 ganglion 12 ganglion 13 neurons exposure to ototoxic compounds has been found to cause hc apoptosis , hc necrosis , and damage to the afferent terminals , of differing severity depending on the ototoxicity model . 0 ###LEFT-WALL### 1 exposure 0 ###LEFT-WALL### 7 found 0 ###LEFT-WALL### 12 , 1 exposure 2 to 1 exposure 5 has 2 to 4 compounds 3 ototoxic 4 compounds 5 has 6 been 6 been 7 found 7 found 8 to 8 to 11 apoptosis 9 cause 11 apoptosis 10 hc 11 apoptosis 12 , 16 and 13 hc 14 necrosis 14 necrosis 16 and 15 , 16 and 16 and 17 damage 16 and 18 to 18 to 21 terminals 19 the 21 terminals 20 afferent 21 terminals 21 terminals 23 of 22 , 23 of 23 of 25 severity 23 of 31 . 24 differing 25 severity 25 severity 26 depending 26 depending 27 on 27 on 30 model 28 the 30 model 29 ototoxicity 30 model one major pathway frequently involved in hc apoptosis is the c - [jun] n [-] terminal [kinase] ( jnk ) signaling pathway activated by reactive oxygen species , but other apoptotic pathways can also play a role in ototoxicity . 0 ###LEFT-WALL### 3 pathway 0 ###LEFT-WALL### 9 is 0 ###LEFT-WALL### 29 but 0 ###LEFT-WALL### 40 . 1 one 3 pathway 2 major 3 pathway 3 pathway 5 involved 3 pathway 6 in 3 pathway 9 is 4 frequently 5 involved 6 in 8 apoptosis 7 hc 8 apoptosis 9 is 22 pathway 10 the 22 pathway 11 c 12 - 12 - 14 n 12 - 22 pathway 16 terminal 19 jnk 16 terminal 22 pathway 18 ( 19 jnk 19 jnk 20 ) 21 signaling 22 pathway 22 pathway 23 activated 23 activated 24 by 24 by 27 species 25 reactive 26 oxygen 26 oxygen 27 species 28 , 29 but 29 but 32 pathways 29 but 35 play 30 other 32 pathways 31 apoptotic 32 pathways 32 pathways 33 can 33 can 35 play 34 also 35 play 35 play 37 role 35 play 38 in 36 a 37 role 38 in 39 ototoxicity moreover , little is known about the effects of chronic low - dose exposure . 0 ###LEFT-WALL### 3 little 0 ###LEFT-WALL### 5 known 0 ###LEFT-WALL### 15 . 1 moreover 2 , 1 moreover 3 little 3 little 4 is 4 is 5 known 5 known 6 about 6 about 8 effects 7 the 8 effects 8 effects 9 of 9 of 14 exposure 10 chronic 13 dose 11 low 12 - 11 low 13 dose 13 dose 14 exposure in rodent vestibular epithelia , extrusion of live hcs from the sensory epithelium may be the predominant form of cell demise during chronic ototoxicity . 0 ###LEFT-WALL### 6 extrusion 0 ###LEFT-WALL### 15 be 0 ###LEFT-WALL### 25 . 1 in 4 epithelia 1 in 5 , 1 in 6 extrusion 2 rodent 4 epithelia 3 vestibular 4 epithelia 6 extrusion 7 of 6 extrusion 14 may 7 of 9 hcs 8 live 9 hcs 9 hcs 10 from 10 from 13 epithelium 11 the 13 epithelium 12 sensory 13 epithelium 14 may 15 be 15 be 18 form 16 the 18 form 17 predominant 18 form 18 form 19 of 19 of 21 demise 20 cell 21 demise 21 demise 22 during 22 during 24 ototoxicity 23 chronic 24 ototoxicity in addition , greater involvement of the afferent terminals may occur , particularly the calyx units [contacting] type [i] vestibular hcs . 0 ###LEFT-WALL### 5 involvement 0 ###LEFT-WALL### 11 occur 0 ###LEFT-WALL### 12 , 0 ###LEFT-WALL### 22 . 1 in 2 addition 1 in 3 , 1 in 5 involvement 4 greater 5 involvement 5 involvement 6 of 5 involvement 10 may 6 of 9 terminals 7 the 9 terminals 8 afferent 9 terminals 10 may 11 occur 12 , 16 units 12 , 18 type 13 particularly 16 units 14 the 16 units 15 calyx 16 units 16 units 18 type 18 type 21 hcs 20 vestibular 21 hcs as glutamate is the neurotransmitter in this [synapse] , excitotoxic phenomena may participate in afferent and ganglion neuron damage . 0 ###LEFT-WALL### 11 phenomena 0 ###LEFT-WALL### 13 participate 0 ###LEFT-WALL### 20 . 1 as 2 glutamate 1 as 3 is 1 as 11 phenomena 2 glutamate 3 is 3 is 5 neurotransmitter 4 the 5 neurotransmitter 6 in 7 this 6 in 9 , 6 in 11 phenomena 10 excitotoxic 11 phenomena 11 phenomena 12 may 12 may 13 participate 13 participate 14 in 14 in 16 and 15 afferent 16 and 16 and 19 damage 17 ganglion 19 damage 18 neuron 19 damage better knowledge of the events that take place in chronic ototoxicity is of great interest , as it will increase understanding of the sensory loss associated with chronic exposure and aging . 0 ###LEFT-WALL### 2 knowledge 0 ###LEFT-WALL### 12 is 0 ###LEFT-WALL### 16 , 0 ###LEFT-WALL### 32 . 1 better 2 knowledge 2 knowledge 3 of 2 knowledge 12 is 3 of 5 events 4 the 5 events 5 events 6 that 5 events 7 take 6 that 7 take 7 take 8 place 7 take 9 in 9 in 11 ototoxicity 10 chronic 11 ototoxicity 12 is 13 of 13 of 15 interest 14 great 15 interest 16 , 21 understanding 16 , 26 associated 17 as 18 it 17 as 20 increase 17 as 21 understanding 18 it 19 will 19 will 20 increase 21 understanding 22 of 21 understanding 26 associated 22 of 25 loss 23 the 25 loss 24 sensory 25 loss 26 associated 27 with 27 with 30 and 28 chronic 29 exposure 29 exposure 30 and 30 and 31 aging the incidence of [both] diabetes mellitus ( dm ) and dementia increases with aging and the incidence of dementia are higher in people with diabetes . 0 ###LEFT-WALL### 15 and 0 ###LEFT-WALL### 20 are 0 ###LEFT-WALL### 26 . 1 the 2 incidence 2 incidence 3 of 2 incidence 10 and 3 of 6 mellitus 5 diabetes 6 mellitus 6 mellitus 8 dm 7 ( 8 dm 8 dm 9 ) 10 and 12 increases 10 and 13 with 10 and 15 and 11 dementia 12 increases 13 with 14 aging 15 and 17 incidence 15 and 18 of 15 and 20 are 16 the 17 incidence 18 of 19 dementia 20 are 21 higher 21 higher 22 in 22 in 23 people 23 people 24 with 24 with 25 diabetes epidemiological and pathological data suggest that dm contributes to mild cognitive impairment ( mci ) and dementia . 0 ###LEFT-WALL### 16 and 0 ###LEFT-WALL### 18 . 1 epidemiological 2 and 2 and 3 pathological 2 and 4 data 2 and 8 contributes 2 and 16 and 4 data 5 suggest 5 suggest 6 that 6 that 7 dm 6 that 8 contributes 7 dm 8 contributes 8 contributes 9 to 9 to 12 impairment 10 mild 12 impairment 11 cognitive 12 impairment 12 impairment 14 mci 13 ( 14 mci 14 mci 15 ) 16 and 17 dementia dm seems to be an independent risk factor for mci and alzheimer 's disease ( ad ) and is associated with more rapid cognitive [decline] . 0 ###LEFT-WALL### 1 dm 0 ###LEFT-WALL### 18 and 0 ###LEFT-WALL### 26 . 1 dm 18 and 2 seems 3 to 2 seems 4 be 2 seems 18 and 3 to 4 be 4 be 11 and 5 an 8 factor 6 independent 8 factor 7 risk 8 factor 8 factor 9 for 8 factor 11 and 9 for 10 mci 11 and 14 disease 11 and 16 ad 12 alzheimer 13 's 13 's 14 disease 15 ( 16 ad 16 ad 17 ) 18 and 19 is 19 is 20 associated 20 associated 21 with 20 associated 24 cognitive 21 with 22 more 21 with 23 rapid recent evidence points out that insulin affects central nervous system functions , and can modulate cognitive functions . 0 ###LEFT-WALL### 2 evidence 0 ###LEFT-WALL### 4 out 0 ###LEFT-WALL### 18 . 1 recent 2 evidence 2 evidence 4 out 3 points 4 out 4 out 5 that 5 that 6 insulin 5 that 13 and 6 insulin 13 and 7 affects 11 functions 7 affects 13 and 8 central 10 system 9 nervous 10 system 10 system 11 functions 12 , 13 and 13 and 14 can 14 can 15 modulate 15 modulate 17 functions 16 cognitive 17 functions impaired insulin signaling and insulin resistance in brain have been found to play an important role in the pathogenesis of ad . 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 11 found 0 ###LEFT-WALL### 22 . 1 impaired 2 insulin 2 insulin 3 signaling 2 insulin 4 and 4 and 6 resistance 4 and 7 in 4 and 9 have 5 insulin 6 resistance 7 in 8 brain 9 have 10 been 10 been 11 found 11 found 12 to 11 found 17 in 12 to 13 play 13 play 16 role 14 an 15 important 14 an 16 role 15 important 16 role 17 in 19 pathogenesis 18 the 19 pathogenesis 19 pathogenesis 20 of 20 of 21 ad human studies have shown that some oral antidiabetic medications can improve cognition in patients with mci and ad . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 4 shown 0 ###LEFT-WALL### 19 . 1 human 2 studies 2 studies 3 have 3 have 4 shown 4 shown 5 that 5 that 9 medications 5 that 11 improve 6 some 9 medications 7 oral 9 medications 8 antidiabetic 9 medications 9 medications 10 can 10 can 11 improve 11 improve 12 cognition 11 improve 13 in 13 in 17 and 14 patients 15 with 14 patients 17 and 15 with 16 mci 17 and 18 ad intranasal insulin has also been shown to improve memory and cognitive abilities in mci and ad patients . 0 ###LEFT-WALL### 2 insulin 0 ###LEFT-WALL### 6 shown 0 ###LEFT-WALL### 18 . 1 intranasal 2 insulin 2 insulin 3 has 3 has 5 been 4 also 5 been 5 been 6 shown 6 shown 7 to 7 to 8 improve 8 improve 15 and 9 memory 10 and 10 and 12 abilities 10 and 13 in 10 and 15 and 11 cognitive 12 abilities 13 in 14 mci 15 and 17 patients 16 ad 17 patients while it remains unclear whether management of diabetes will reduce the incidence of mci and ad , emerging evidence suggests that diabetes therapies may improve [cognitive] function . 0 ###LEFT-WALL### 19 evidence 0 ###LEFT-WALL### 28 . 1 while 2 it 1 while 3 remains 1 while 17 , 1 while 19 evidence 2 it 3 remains 3 remains 4 unclear 4 unclear 5 whether 5 whether 6 management 5 whether 10 reduce 6 management 7 of 6 management 9 will 7 of 8 diabetes 9 will 10 reduce 10 reduce 15 and 11 the 12 incidence 12 incidence 13 of 12 incidence 15 and 13 of 14 mci 15 and 16 ad 18 emerging 19 evidence 19 evidence 20 suggests 20 suggests 21 that 21 that 22 diabetes 21 that 27 function 22 diabetes 23 therapies 22 diabetes 25 improve 23 therapies 24 may 24 may 25 improve this review defines water - loss and salt - loss dehydration . 0 ###LEFT-WALL### 2 review 0 ###LEFT-WALL### 3 defines 0 ###LEFT-WALL### 9 - 1 this 2 review 2 review 3 defines 3 defines 4 water 4 water 7 and 5 - 7 and 6 loss 7 and 7 and 8 salt 7 and 9 - 9 - 11 dehydration 9 - 12 . 10 loss 11 dehydration for older people serum osmolality [appears] the most appropriate gold standard for diagnosis of water - loss dehydration , but clear signs of early dehydration have not been developed . 0 ###LEFT-WALL### 22 signs 0 ###LEFT-WALL### 29 developed 0 ###LEFT-WALL### 30 . 1 for 5 osmolality 1 for 22 signs 2 older 5 osmolality 3 people 4 serum 4 serum 5 osmolality 7 the 8 most 8 most 22 signs 9 appropriate 22 signs 10 gold 22 signs 11 standard 12 for 11 standard 20 but 12 for 13 diagnosis 13 diagnosis 14 of 14 of 15 water 15 water 18 dehydration 16 - 18 dehydration 17 loss 18 dehydration 18 dehydration 19 , 20 but 21 clear 20 but 22 signs 22 signs 23 of 22 signs 26 have 23 of 25 dehydration 24 early 25 dehydration 26 have 27 not 26 have 28 been 28 been 29 developed in older adults , lower muscle mass , reduced kidney function , physical and cognitive disabilities , blunted thirst , and polypharmacy all increase dehydration risk . 0 ###LEFT-WALL### 21 and 0 ###LEFT-WALL### 24 increase 0 ###LEFT-WALL### 27 . 1 in 14 and 1 in 17 , 1 in 21 and 2 older 3 adults 3 adults 4 , 4 , 7 mass 4 , 8 , 5 lower 6 muscle 6 muscle 7 mass 8 , 11 function 8 , 12 , 9 reduced 10 kidney 10 kidney 11 function 12 , 13 physical 12 , 14 and 14 and 16 disabilities 15 cognitive 16 disabilities 18 blunted 19 thirst 19 thirst 21 and 20 , 21 and 21 and 22 polypharmacy 21 and 24 increase 23 all 24 increase 24 increase 26 risk 25 dehydration 26 risk cross - sectional studies suggest a water [-] loss dehydration prevalence of 20 - 30 % in this population . 0 ###LEFT-WALL### 4 studies 0 ###LEFT-WALL### 5 suggest 0 ###LEFT-WALL### 20 . 1 cross 2 - 1 cross 4 studies 3 sectional 4 studies 4 studies 5 suggest 5 suggest 11 prevalence 5 suggest 17 in 6 a 7 water 6 a 11 prevalence 7 water 11 prevalence 9 loss 11 prevalence 10 dehydration 11 prevalence 11 prevalence 12 of 12 of 16 % 13 20 14 - 14 - 15 30 14 - 16 % 17 in 19 population 18 this 19 population water - loss dehydration is associated with higher mortality , morbidity and disability in older people , but evidence [is] still needed that this relationship is causal . 0 ###LEFT-WALL### 4 dehydration 0 ###LEFT-WALL### 6 associated 1 water 2 - 1 water 4 dehydration 3 loss 4 dehydration 4 dehydration 5 is 5 is 6 associated 6 associated 7 with 6 associated 14 in 7 with 12 and 8 higher 9 mortality 9 mortality 10 , 10 , 11 morbidity 10 , 12 and 12 and 13 disability 14 in 16 people 15 older 16 people 16 people 18 but 17 , 18 but 18 but 19 evidence 18 but 28 . 19 evidence 21 still 19 evidence 22 needed 19 evidence 23 that 23 that 25 relationship 23 that 26 is 24 this 25 relationship 25 relationship 26 is 26 is 27 causal there are a variety of ways we may be able to help older people reduce their risk of dehydration by recognising that they are not drinking enough , and being helped to drink more . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 are 0 ###LEFT-WALL### 35 . 1 there 2 are 2 are 29 and 3 a 4 variety 4 variety 5 of 4 variety 10 able 4 variety 29 and 5 of 6 ways 6 ways 7 we 6 ways 9 be 7 we 8 may 8 may 9 be 10 able 11 to 10 able 15 reduce 11 to 12 help 12 help 14 people 12 help 15 reduce 13 older 14 people 15 reduce 17 risk 16 their 17 risk 17 risk 18 of 17 risk 20 by 17 risk 22 that 18 of 19 dehydration 20 by 21 recognising 22 that 23 they 22 that 24 are 23 they 24 are 24 are 25 not 24 are 27 enough 25 not 26 drinking 28 , 29 and 29 and 30 being 29 and 31 helped 29 and 32 to 29 and 33 drink 32 to 33 drink 33 drink 34 more strategies to increase fluid intake in residential care homes include identifying and overcoming individual and institutional barriers to drinking , such as being worried about not reaching the toilet in time , physical inability to make or to reach drinks , and reduced social drinking and drinking pleasure . 0 ###LEFT-WALL### 1 strategies 0 ###LEFT-WALL### 9 homes 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 49 . 1 strategies 2 to 1 strategies 6 in 1 strategies 9 homes 2 to 5 intake 3 increase 4 fluid 4 fluid 5 intake 6 in 8 care 7 residential 8 care 9 homes 11 identifying 10 include 11 identifying 12 and 13 overcoming 12 and 24 worried 13 overcoming 15 and 13 overcoming 22 as 13 overcoming 24 worried 14 individual 15 and 15 and 17 barriers 15 and 20 , 16 institutional 17 barriers 17 barriers 18 to 18 to 19 drinking 21 such 22 as 22 as 23 being 24 worried 25 about 24 worried 34 inability 24 worried 42 and 25 about 26 not 26 not 27 reaching 27 reaching 29 toilet 28 the 29 toilet 30 in 31 time 30 in 32 , 30 in 34 inability 33 physical 34 inability 34 inability 35 to 34 inability 37 or 34 inability 42 and 35 to 37 or 36 make 37 or 37 or 38 to 37 or 39 reach 38 to 39 reach 40 drinks 42 and 41 , 42 and 42 and 43 reduced 43 reduced 48 pleasure 44 social 48 pleasure 45 drinking 46 and 46 and 47 drinking 46 and 48 pleasure research needs are discussed , some of which will be addressed by the fp7 - funded nu - age ( new dietary strategies addressing the specific needs of elderly population for [a] healthy ageing in europe ) [trial] . 0 ###LEFT-WALL### 1 research 0 ###LEFT-WALL### 16 funded 0 ###LEFT-WALL### 39 . 1 research 2 needs 1 research 3 are 1 research 4 discussed 1 research 6 some 1 research 16 funded 2 needs 3 are 5 , 6 some 6 some 7 of 6 some 15 - 7 of 8 which 8 which 9 will 9 will 10 be 10 be 11 addressed 11 addressed 12 by 12 by 14 fp7 13 the 14 fp7 16 funded 19 age 17 nu 19 age 18 - 19 age 19 age 23 strategies 20 ( 23 strategies 21 new 23 strategies 22 dietary 23 strategies 23 strategies 24 addressing 23 strategies 37 ) 24 addressing 27 needs 25 the 27 needs 26 specific 27 needs 27 needs 28 of 27 needs 35 in 28 of 30 population 29 elderly 30 population 30 population 31 for 31 for 34 ageing 33 healthy 34 ageing 35 in 36 europe objective : sleep problems are associated with mortality in western populations . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 2 : 4 problems 2 : 6 associated 2 : 12 . 3 sleep 4 problems 4 problems 5 are 5 are 6 associated 6 associated 7 with 6 associated 9 in 7 with 8 mortality 9 in 11 populations 10 western 11 populations in low - resource settings , evidence of sleep problems and their potential association with mortality is lacking . 0 ###LEFT-WALL### 7 evidence 0 ###LEFT-WALL### 17 is 0 ###LEFT-WALL### 19 . 1 in 5 settings 1 in 6 , 1 in 7 evidence 2 low 3 - 2 low 4 resource 4 resource 5 settings 7 evidence 8 of 7 evidence 17 is 8 of 11 and 9 sleep 10 problems 10 problems 11 and 11 and 14 association 11 and 15 with 12 their 14 association 13 potential 14 association 15 with 16 mortality 17 is 18 lacking our study aimed to fill this gap by examining the prospective association of sleep problems with mortality among older adults in rural south africa , as well as potential sex differences in this association . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 aimed 0 ###LEFT-WALL### 25 , 0 ###LEFT-WALL### 35 . 1 our 2 study 2 study 3 aimed 3 aimed 4 to 3 aimed 5 fill 4 to 5 fill 5 fill 7 gap 5 fill 8 by 5 fill 18 among 6 this 7 gap 8 by 9 examining 9 examining 12 association 9 examining 16 with 10 the 12 association 11 prospective 12 association 12 association 13 of 13 of 15 problems 14 sleep 15 problems 16 with 17 mortality 18 among 20 adults 19 older 20 adults 20 adults 21 in 21 in 24 africa 22 rural 24 africa 23 south 24 africa 25 , 30 sex 26 as 27 well 27 well 28 as 28 as 29 potential 28 as 30 sex 30 sex 31 differences 30 sex 32 in 32 in 34 association 33 this 34 association methods : the study was conducted in 2006 in agincourt ( south africa ) , as part of the health and demographic surveillance system . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 4 study 2 : 6 conducted 3 the 4 study 4 study 5 was 5 was 6 conducted 6 conducted 7 in 6 conducted 9 in 7 in 8 2006 9 in 10 agincourt 10 agincourt 13 africa 10 agincourt 16 as 11 ( 13 africa 12 south 13 africa 13 africa 14 ) 15 , 16 as 16 as 21 and 16 as 25 . 17 part 18 of 17 part 21 and 18 of 20 health 19 the 20 health 21 and 24 system 22 demographic 23 surveillance 23 surveillance 24 system a community [-] wide sample of 4044 men and women aged 50 years or older participated in the survey . 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 16 participated 0 ###LEFT-WALL### 20 . 1 a 5 sample 2 community 5 sample 4 wide 5 sample 5 sample 6 of 5 sample 9 and 6 of 8 men 7 4044 8 men 9 and 10 women 9 and 11 aged 9 and 16 participated 11 aged 14 or 12 50 13 years 13 years 14 or 14 or 15 older 16 participated 17 in 17 in 19 survey 18 the 19 survey two measures of sleep quality over the last 30 days were assessed alongside sociodemographic variables , measures of quality of life ( qol ) , and functional ability . 0 ###LEFT-WALL### 2 measures 0 ###LEFT-WALL### 12 assessed 0 ###LEFT-WALL### 29 . 1 two 2 measures 2 measures 3 of 2 measures 11 were 3 of 5 quality 4 sleep 5 quality 5 quality 6 over 6 over 10 days 7 the 8 last 7 the 9 30 9 30 10 days 11 were 12 assessed 12 assessed 13 alongside 13 alongside 26 and 14 sociodemographic 15 variables 15 variables 16 , 16 , 17 measures 16 , 26 and 17 measures 18 of 18 of 19 quality 19 quality 20 of 19 quality 23 qol 20 of 21 life 22 ( 23 qol 23 qol 24 ) 25 , 26 and 26 and 28 ability 27 functional 28 ability cox proportional hazard models were used to estimate hazard ratios ( hr [ )(and 95 % confidence intervals ( ci ) for mortality risk over time associated with the two sleep measures at baseline , while allowing adjustment for other covariates . 0 ###LEFT-WALL### 1 cox 1 cox 3 hazard 2 proportional 3 hazard 3 hazard 4 models 3 hazard 8 estimate 4 models 5 were 5 were 6 used 6 used 7 to 6 used 8 estimate 7 to 8 estimate 8 estimate 10 ratios 8 estimate 22 for 8 estimate 36 while 9 hazard 10 ratios 10 ratios 14 )(and 11 ( 14 )(and 12 hr 14 )(and 14 )(and 18 intervals 14 )(and 20 ci 14 )(and 21 ) 15 95 18 intervals 16 % 17 confidence 17 confidence 18 intervals 19 ( 20 ci 20 ci 21 ) 22 for 24 risk 23 mortality 24 risk 24 risk 25 over 24 risk 27 associated 24 risk 28 with 25 over 26 time 28 with 32 measures 29 the 30 two 30 two 32 measures 31 sleep 32 measures 32 measures 33 at 33 at 34 baseline 35 , 36 while 36 while 37 allowing 36 while 42 . 37 allowing 38 adjustment 37 allowing 39 for 39 for 41 covariates 40 other 41 covariates results : overall , 394 deaths occurred during 3 years of follow - up . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 4 , 1 results 2 : 2 : 3 overall 4 , 5 394 4 , 12 follow 5 394 6 deaths 5 394 11 of 5 394 12 follow 6 deaths 7 occurred 7 occurred 8 during 8 during 10 years 9 3 10 years 10 years 11 of 12 follow 14 up 13 - 14 up 14 up 15 . both men and women reporting severe/extreme nocturnal sleep problems ( [vs] none/mild/moderate ) experienced a significantly greater mortality risk in models adjusted for sociodemographic variables only ( hr , 1.65 [ 95 % ci , 1.18 - 2.31 ] and hr , 1.42 [ 95 % ci , 1.07 - 1.88 ] , respectively ) . 0 ###LEFT-WALL### 2 men 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 56 . 1 both 2 men 3 and 4 women 3 and 14 experienced 4 women 5 reporting 4 women 14 experienced 5 reporting 9 problems 6 severe/extreme 9 problems 7 nocturnal 8 sleep 8 sleep 9 problems 9 problems 12 none/mild/moderate 10 ( 12 none/mild/moderate 12 none/mild/moderate 13 ) 14 experienced 40 and 14 experienced 50 - 14 experienced 54 respectively 15 a 19 risk 16 significantly 17 greater 17 greater 18 mortality 18 mortality 19 risk 19 risk 20 in 19 risk 40 and 20 in 21 models 21 models 22 adjusted 21 models 28 hr 22 adjusted 23 for 22 adjusted 26 only 23 for 25 variables 24 sociodemographic 25 variables 27 ( 28 hr 28 hr 30 1.65 28 hr 39 ] 29 , 30 1.65 30 1.65 34 ci 30 1.65 37 - 30 1.65 39 ] 31 [ 34 ci 32 95 34 ci 33 % 34 ci 34 ci 35 , 35 , 37 - 36 1.18 37 - 37 - 38 2.31 37 - 39 ] 40 and 41 hr 41 hr 43 1.42 42 , 43 1.42 43 1.42 47 ci 43 1.42 48 , 44 [ 47 ci 45 95 47 ci 46 % 47 ci 47 ci 48 , 48 , 50 - 49 1.07 50 - 50 - 51 1.88 50 - 52 ] 53 , 54 respectively 54 respectively 55 ) however , these associations were nonsignificant in fully adjusted models ( hr , 1.23 [ 95 % ci , 0.85 - 1.79 ] and hr , 1.07 [ 95 % ci , 0.78 - 1.47 ] , respectively ) . 0 ###LEFT-WALL### 4 associations 0 ###LEFT-WALL### 5 were 0 ###LEFT-WALL### 40 . 1 however 2 , 1 however 4 associations 3 these 4 associations 4 associations 5 were 5 were 6 nonsignificant 6 nonsignificant 7 in 6 nonsignificant 34 - 6 nonsignificant 38 respectively 7 in 10 models 8 fully 9 adjusted 9 adjusted 10 models 10 models 24 and 11 ( 24 and 12 hr 14 1.23 12 hr 24 and 13 , 14 1.23 14 1.23 18 ci 14 1.23 21 - 14 1.23 23 ] 15 [ 18 ci 16 95 18 ci 17 % 18 ci 18 ci 19 , 19 , 21 - 20 0.85 21 - 21 - 22 1.79 21 - 23 ] 24 and 25 hr 24 and 32 , 25 hr 27 1.07 26 , 27 1.07 27 1.07 31 ci 27 1.07 32 , 28 [ 31 ci 29 95 31 ci 30 % 31 ci 31 ci 32 , 32 , 34 - 33 0.78 34 - 34 - 35 1.47 34 - 36 ] 37 , 38 respectively 38 respectively 39 ) men who reported severe/extreme difficulty related to daytime function ( [vs] none/mild/moderate ) experienced a 2 [-] fold increased mortality risk ( hr , [2.01] [ 95 % ci , 1.32 - 3.07 ] ) [in] fully adjusted models , [whereas] no significant association was observed for women ( 1.16 [ 95 % ci , 0.80 - 1.67 ] ) . 0 ###LEFT-WALL### 1 men 0 ###LEFT-WALL### 4 severe/extreme 0 ###LEFT-WALL### 6 related 1 men 2 who 1 men 3 reported 1 men 4 severe/extreme 2 who 3 reported 5 difficulty 6 related 6 related 7 to 7 to 8 daytime 8 daytime 9 function 8 daytime 14 experienced 9 function 12 none/mild/moderate 9 function 14 experienced 10 ( 12 none/mild/moderate 12 none/mild/moderate 13 ) 14 experienced 21 risk 15 a 21 risk 16 2 19 increased 18 fold 19 increased 19 increased 21 risk 20 mortality 21 risk 21 risk 23 hr 21 risk 29 ci 22 ( 23 hr 23 hr 24 , 26 [ 29 ci 27 95 29 ci 28 % 29 ci 29 ci 31 1.32 29 ci 40 , 30 , 31 1.32 31 1.32 33 3.07 31 1.32 35 ) 32 - 33 3.07 33 3.07 34 ] 37 fully 38 adjusted 38 adjusted 39 models 38 adjusted 40 , 40 , 46 observed 42 no 44 association 43 significant 44 association 44 association 45 was 45 was 46 observed 46 observed 47 for 47 for 48 women 48 women 50 1.16 49 ( 50 1.16 50 1.16 54 ci 50 1.16 61 . 51 [ 54 ci 52 95 54 ci 53 % 54 ci 54 ci 56 0.80 54 ci 61 . 55 , 56 0.80 56 0.80 58 1.67 56 0.80 60 ) 57 - 58 1.67 58 1.67 59 ] conclusions : in this population , nocturnal sleep problems were not associated with mortality once analyses were adjusted for qol , functional ability , and psychologic comorbidities . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 6 , 0 ###LEFT-WALL### 28 . 1 conclusions 2 : 2 : 3 in 3 in 5 population 4 this 5 population 6 , 9 problems 6 , 10 were 6 , 21 , 7 nocturnal 8 sleep 8 sleep 9 problems 9 problems 10 were 10 were 11 not 10 were 13 with 10 were 15 once 10 were 19 for 11 not 12 associated 13 with 14 mortality 15 once 16 analyses 15 once 17 were 16 analyses 17 were 17 were 18 adjusted 19 for 20 qol 21 , 25 and 22 functional 23 ability 23 ability 25 and 24 , 25 and 25 and 27 comorbidities 26 psychologic 27 comorbidities by contrast , severe or extreme problems with feeling unrested or unrefreshed during the day were associated with [a] 2 - fold increased mortality risk , but this association was only significant in men . 0 ###LEFT-WALL### 5 or 0 ###LEFT-WALL### 17 associated 0 ###LEFT-WALL### 27 but 0 ###LEFT-WALL### 35 . 1 by 2 contrast 1 by 3 , 1 by 5 or 4 severe 5 or 5 or 6 extreme 5 or 7 problems 5 or 12 unrefreshed 5 or 16 were 7 problems 8 with 7 problems 11 or 8 with 9 feeling 10 unrested 11 or 11 or 12 unrefreshed 12 unrefreshed 13 during 13 during 15 day 14 the 15 day 16 were 17 associated 17 associated 18 with 18 with 20 2 20 2 25 risk 21 - 25 risk 22 fold 25 risk 23 increased 24 mortality 24 mortality 25 risk 25 risk 26 , 27 but 29 association 27 but 30 was 28 this 29 association 29 association 30 was 30 was 31 only 30 was 32 significant 32 significant 33 in 33 in 34 men cd200 is a transmembrane protein that belongs to the immunoglobulin family of proteins and is ubiquitously expressed on a variety of cell types . 0 ###LEFT-WALL### 1 cd200 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 24 . 1 cd200 2 is 2 is 5 protein 3 a 4 transmembrane 3 a 5 protein 4 transmembrane 5 protein 5 protein 6 that 5 protein 14 and 6 that 14 and 7 belongs 8 to 7 belongs 14 and 8 to 11 family 9 the 11 family 10 immunoglobulin 11 family 11 family 12 of 12 of 13 proteins 14 and 15 is 15 is 17 expressed 16 ubiquitously 17 expressed 17 expressed 18 on 18 on 20 variety 19 a 20 variety 20 variety 21 of 21 of 23 types 22 cell 23 types upon interaction with its receptors ( cd200rs ) expressed on myeloid - derived cells and t lymphocytes , an immunoregulatory signal is delivered to receptor [-] expressing cells . 0 ###LEFT-WALL### 21 signal 0 ###LEFT-WALL### 23 delivered 0 ###LEFT-WALL### 29 . 1 upon 2 interaction 1 upon 21 signal 2 interaction 3 with 2 interaction 7 cd200rs 3 with 5 receptors 4 its 5 receptors 6 ( 7 cd200rs 7 cd200rs 8 ) 9 expressed 10 on 9 expressed 18 , 9 expressed 21 signal 10 on 17 lymphocytes 11 myeloid 12 - 11 myeloid 14 cells 13 derived 14 cells 14 cells 15 and 15 and 16 t 15 and 17 lymphocytes 19 an 20 immunoregulatory 19 an 21 signal 20 immunoregulatory 21 signal 21 signal 22 is 22 is 23 delivered 23 delivered 24 to 24 to 28 cells 25 receptor 27 expressing 27 expressing 28 cells previous studies have implicated a role for cd200:cd200r in the regulation of the expression of mrna markers of osteoclastogenesis/osteoblastogenesis , following interaction of cd200 ( on osteoblast precursors ) with cd200r1 ( on osteoclast precursors ) . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 4 implicated 0 ###LEFT-WALL### 37 . 1 previous 2 studies 2 studies 3 have 3 have 4 implicated 4 implicated 6 role 4 implicated 7 for 4 implicated 9 in 5 a 6 role 7 for 8 cd200:cd200r 9 in 11 regulation 10 the 11 regulation 11 regulation 12 of 11 regulation 15 of 11 regulation 18 of 11 regulation 21 following 12 of 14 expression 13 the 14 expression 15 of 17 markers 16 mrna 17 markers 18 of 19 osteoclastogenesis/osteoblastogenesis 20 , 21 following 21 following 22 interaction 21 following 30 with 21 following 36 ) 22 interaction 23 of 23 of 24 cd200 24 cd200 26 on 25 ( 26 on 26 on 28 precursors 26 on 29 ) 27 osteoblast 28 precursors 30 with 31 cd200r1 31 cd200r1 33 on 32 ( 33 on 33 on 35 precursors 33 on 36 ) 34 osteoclast 35 precursors signaling of cd200r1 is hypothesized to attenuate osteoclastogenesis . 0 ###LEFT-WALL### 1 signaling 0 ###LEFT-WALL### 5 hypothesized 0 ###LEFT-WALL### 9 . 1 signaling 2 of 1 signaling 4 is 2 of 3 cd200r1 4 is 5 hypothesized 5 hypothesized 6 to 6 to 7 attenuate 7 attenuate 8 osteoclastogenesis we have investigated whether levels of soluble forms of cd200 [and/or] cd200r1 ( scd200 , scd200r1 ) are altered in volunteers undergoing 6 ° head down tilt bed rest to mimic conditions of microgravity known to be associated with preferential osteoclastogenesis and whether countermeasures , reported to be beneficial in attenuation of bone loss under microgravity conditions , would lead to altered scd200 and scd200r1 levels . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 investigated 0 ###LEFT-WALL### 67 . 1 we 2 have 2 have 3 investigated 3 investigated 4 whether 3 investigated 25 head 3 investigated 26 down 3 investigated 30 to 4 whether 5 levels 4 whether 19 altered 5 levels 6 of 5 levels 16 scd200r1 5 levels 18 are 6 of 8 forms 7 soluble 8 forms 8 forms 9 of 9 of 12 cd200r1 10 cd200 12 cd200r1 12 cd200r1 14 scd200 13 ( 14 scd200 14 scd200 15 , 15 , 16 scd200r1 16 scd200r1 17 ) 18 are 19 altered 19 altered 20 in 20 in 21 volunteers 21 volunteers 22 undergoing 22 undergoing 24 ° 23 6 24 ° 26 down 29 rest 27 tilt 28 bed 28 bed 29 rest 30 to 45 , 31 mimic 44 countermeasures 31 mimic 45 , 32 conditions 33 of 32 conditions 42 and 33 of 34 microgravity 34 microgravity 35 known 35 known 36 to 35 known 38 associated 36 to 37 be 37 be 38 associated 38 associated 39 with 39 with 41 osteoclastogenesis 40 preferential 41 osteoclastogenesis 42 and 43 whether 42 and 44 countermeasures 45 , 46 reported 46 reported 47 to 46 reported 61 to 47 to 58 , 48 be 49 beneficial 48 be 58 , 49 beneficial 50 in 49 beneficial 55 under 50 in 51 attenuation 51 attenuation 52 of 52 of 54 loss 53 bone 54 loss 55 under 57 conditions 56 microgravity 57 conditions 58 , 59 would 59 would 60 lead 61 to 64 and 62 altered 63 scd200 63 scd200 64 and 64 and 66 levels 65 scd200r1 66 levels our data suggest that , as predicted , scd200 levels fall under bed rest conditions while scd200r1 levels rise . 0 ###LEFT-WALL### 2 data 0 ###LEFT-WALL### 3 suggest 0 ###LEFT-WALL### 20 . 1 our 2 data 2 data 3 suggest 3 suggest 4 that 4 that 10 levels 4 that 11 fall 5 , 6 as 6 as 7 predicted 6 as 8 , 6 as 10 levels 7 predicted 8 , 9 scd200 10 levels 10 levels 11 fall 11 fall 12 under 11 fall 16 while 12 under 15 conditions 13 bed 15 conditions 14 rest 15 conditions 16 while 18 levels 16 while 19 rise 17 scd200r1 18 levels 18 levels 19 rise in subjects undergoing 30 - minute [per] day continuous centrifugation protocols , as a countermeasure to attenuate changes which may lead to bone loss , these alterations in scd200 and scd200r1 levels seen under conditions of bed rest were abolished or attenuated . 0 ###LEFT-WALL### 2 subjects 0 ###LEFT-WALL### 21 lead 1 in 2 subjects 2 subjects 3 undergoing 2 subjects 13 as 2 subjects 16 to 2 subjects 17 attenuate 2 subjects 21 lead 3 undergoing 4 30 4 30 11 protocols 5 - 11 protocols 6 minute 11 protocols 8 day 10 centrifugation 9 continuous 10 centrifugation 10 centrifugation 11 protocols 11 protocols 12 , 13 as 15 countermeasure 14 a 15 countermeasure 16 to 17 attenuate 17 attenuate 18 changes 18 changes 19 which 18 changes 20 may 19 which 20 may 21 lead 22 to 21 lead 24 loss 22 to 23 bone 24 loss 30 and 25 , 30 and 26 these 27 alterations 27 alterations 28 in 27 alterations 30 and 28 in 29 scd200 30 and 31 scd200r1 30 and 32 levels 30 and 41 or 30 and 43 . 32 levels 33 seen 32 levels 34 under 32 levels 36 of 32 levels 39 were 34 under 35 conditions 36 of 38 rest 37 bed 38 rest 39 were 41 or 40 abolished 41 or 41 or 42 attenuated our results suggest that measurement of scd200 and/or scd200r1 may prove a useful and rapid means of monitoring subjects at risk of bone loss and/or accessing the efficacy of treatment regimes designed to counter bone loss . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 32 designed 0 ###LEFT-WALL### 37 . 1 our 2 results 2 results 3 suggest 3 suggest 5 measurement 3 suggest 8 and/or 4 that 5 measurement 5 measurement 6 of 6 of 7 scd200 8 and/or 9 scd200r1 9 scd200r1 10 may 10 may 11 prove 11 prove 16 means 12 a 16 means 13 useful 14 and 14 and 15 rapid 14 and 16 means 16 means 17 of 17 of 18 monitoring 18 monitoring 19 subjects 18 monitoring 20 at 18 monitoring 25 and/or 20 at 21 risk 21 risk 22 of 22 of 24 loss 23 bone 24 loss 25 and/or 26 accessing 26 accessing 28 efficacy 26 accessing 32 designed 27 the 28 efficacy 28 efficacy 29 of 29 of 31 regimes 30 treatment 31 regimes 32 designed 33 to 32 designed 36 loss 33 to 34 counter 35 bone 36 loss an elevated serum anion gap is known to be associated with hypertension [,] low cardiorespiratory fitness , and decreased renal function . 0 ###LEFT-WALL### 5 gap 0 ###LEFT-WALL### 7 known 0 ###LEFT-WALL### 22 . 1 an 5 gap 2 elevated 3 serum 3 serum 4 anion 4 anion 5 gap 5 gap 6 is 6 is 7 known 7 known 8 to 8 to 9 be 9 be 10 associated 10 associated 11 with 11 with 18 and 12 hypertension 16 fitness 14 low 16 fitness 15 cardiorespiratory 16 fitness 16 fitness 18 and 17 , 18 and 18 and 21 function 19 decreased 21 function 20 renal 21 function we evaluated whether serum ag might be [predictive] of elderly mortality in a community [-] based cohort in korea . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 evaluated 0 ###LEFT-WALL### 20 . 1 we 2 evaluated 2 evaluated 3 whether 3 whether 5 ag 3 whether 7 be 4 serum 5 ag 5 ag 6 might 6 might 7 be 7 be 9 of 7 be 12 in 7 be 18 in 9 of 11 mortality 10 elderly 11 mortality 12 in 17 cohort 13 a 17 cohort 14 community 16 based 16 based 17 cohort 18 in 19 korea we analyzed the available data from 862 elderly people in the korean longitudinal study on health and aging . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 analyzed 0 ###LEFT-WALL### 19 . 1 we 2 analyzed 2 analyzed 5 data 2 analyzed 6 from 2 analyzed 10 in 2 analyzed 15 on 3 the 5 data 4 available 5 data 6 from 9 people 7 862 9 people 8 elderly 9 people 10 in 14 study 11 the 12 korean 12 korean 14 study 13 longitudinal 14 study 15 on 17 and 16 health 17 and 17 and 18 aging the population attributable fraction of death due to high saag was 38.2 % ( 95 % ci 20.7 - 58.2 % ) . 0 ###LEFT-WALL### 4 fraction 0 ###LEFT-WALL### 11 was 0 ###LEFT-WALL### 23 . 1 the 4 fraction 2 population 4 fraction 3 attributable 4 fraction 4 fraction 5 of 4 fraction 11 was 5 of 6 death 6 death 8 to 7 due 8 to 8 to 10 saag 9 high 10 saag 11 was 13 % 12 38.2 13 % 13 % 17 ci 14 ( 17 ci 15 95 17 ci 16 % 17 ci 17 ci 18 20.7 17 ci 21 % 17 ci 22 ) 19 - 21 % 20 58.2 21 % 21 % 22 ) in particular , the participants with high saag had higher cardiovascular and infection - related mortality rates than those with low saag ( hr , 2.11 [;] 95 % ci , 1.06 - 4.19 , and hr , 9.69 [;] 95 % ci , 1.12 - 83.4 , respectively ) . 0 ###LEFT-WALL### 2 particular 0 ###LEFT-WALL### 3 , 0 ###LEFT-WALL### 51 . 1 in 2 particular 3 , 5 participants 3 , 9 had 4 the 5 participants 5 participants 6 with 5 participants 9 had 6 with 8 saag 7 high 8 saag 9 had 17 rates 9 had 18 than 9 had 20 with 9 had 46 - 9 had 49 respectively 10 higher 17 rates 11 cardiovascular 12 and 12 and 13 infection 12 and 14 - 12 and 15 related 12 and 16 mortality 16 mortality 17 rates 18 than 19 those 20 with 22 saag 21 low 22 saag 22 saag 36 and 23 ( 36 and 24 hr 30 ci 24 hr 36 and 25 , 30 ci 26 2.11 30 ci 28 95 30 ci 29 % 30 ci 30 ci 33 - 30 ci 35 , 31 , 33 - 32 1.06 33 - 33 - 34 4.19 33 - 35 , 36 and 37 hr 36 and 43 ci 36 and 44 , 38 , 43 ci 39 9.69 43 ci 41 95 43 ci 42 % 43 ci 43 ci 44 , 45 1.12 46 - 46 - 47 83.4 48 , 49 respectively 49 respectively 50 ) high saag may be an independent predictor of mortality and is associated with higher cardiovascular and infection related mortality in the elderly . 0 ###LEFT-WALL### 2 saag 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 23 . 1 high 2 saag 2 saag 10 and 3 may 4 be 3 may 10 and 4 be 7 predictor 5 an 6 independent 5 an 7 predictor 6 independent 7 predictor 7 predictor 8 of 8 of 9 mortality 10 and 11 is 10 and 13 with 10 and 20 in 11 is 12 associated 13 with 19 mortality 14 higher 19 mortality 15 cardiovascular 16 and 16 and 17 infection 16 and 18 related 18 related 19 mortality 20 in 22 elderly 21 the 22 elderly both the dopaminergic and glutamatergic systems modulate episodic memory consolidation . 0 ###LEFT-WALL### 1 both 0 ###LEFT-WALL### 7 modulate 0 ###LEFT-WALL### 11 . 1 both 2 the 1 both 6 systems 1 both 7 modulate 2 the 6 systems 3 dopaminergic 4 and 4 and 5 glutamatergic 4 and 6 systems 7 modulate 10 consolidation 8 episodic 9 memory 9 memory 10 consolidation evidence from animal studies suggests that these two neurotransmitters may interact in influencing memory performance . 0 ###LEFT-WALL### 1 evidence 0 ###LEFT-WALL### 5 suggests 0 ###LEFT-WALL### 16 . 1 evidence 2 from 1 evidence 5 suggests 2 from 4 studies 3 animal 4 studies 5 suggests 6 that 6 that 9 neurotransmitters 6 that 11 interact 7 these 8 two 8 two 9 neurotransmitters 9 neurotransmitters 10 may 10 may 11 interact 11 interact 12 in 12 in 13 influencing 13 influencing 15 performance 14 memory 15 performance we found a reliable gene - gene interaction , which was observed in older adults only : older individuals carrying genotypes associated with greater d2 and n - methyl - d - aspartate receptor efficacy showed better episodic performance . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 found 0 ###LEFT-WALL### 17 : 0 ###LEFT-WALL### 36 showed 0 ###LEFT-WALL### 40 . 1 we 2 found 2 found 5 gene 3 a 4 reliable 3 a 5 gene 4 reliable 5 gene 5 gene 8 interaction 5 gene 10 which 6 - 8 interaction 7 gene 8 interaction 8 interaction 9 , 9 , 10 which 10 which 11 was 10 which 17 : 11 was 12 observed 12 observed 13 in 12 observed 16 only 13 in 15 adults 14 older 15 adults 17 : 19 individuals 17 : 22 associated 17 : 30 - 18 older 19 individuals 19 individuals 20 carrying 19 individuals 21 genotypes 19 individuals 22 associated 20 carrying 21 genotypes 22 associated 23 with 23 with 26 and 24 greater 25 d2 25 d2 26 and 26 and 27 n 26 and 29 methyl 28 - 29 methyl 29 methyl 30 - 30 - 31 d 30 - 32 - 31 d 32 - 32 - 35 efficacy 33 aspartate 34 receptor 34 receptor 35 efficacy 35 efficacy 36 showed 36 showed 39 performance 37 better 39 performance 38 episodic 39 performance these results are in line with findings showing magnification of genetic effects on memory in old age , presumably as a consequence of reduced brain resources . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 are 1 these 2 results 2 results 3 are 3 are 5 line 3 are 6 with 3 are 15 in 4 in 5 line 6 with 7 findings 7 findings 8 showing 8 showing 9 magnification 8 showing 13 on 9 magnification 10 of 10 of 12 effects 11 genetic 12 effects 13 on 14 memory 15 in 17 age 16 old 17 age 17 age 20 as 18 , 19 presumably 18 , 20 as 20 as 22 consequence 20 as 27 . 21 a 22 consequence 22 consequence 23 of 23 of 26 resources 24 reduced 25 brain 25 brain 26 resources our findings underscore the need for investigating interactive effects of multiple genes to understand individual [difference] in episodic memory . 0 ###LEFT-WALL### 2 findings 0 ###LEFT-WALL### 3 underscore 0 ###LEFT-WALL### 20 . 1 our 2 findings 2 findings 3 underscore 3 underscore 5 need 3 underscore 6 for 4 the 5 need 6 for 7 investigating 7 investigating 9 effects 8 interactive 9 effects 9 effects 10 of 9 effects 15 individual 10 of 12 genes 11 multiple 12 genes 12 genes 13 to 12 genes 14 understand 13 to 14 understand 15 individual 17 in 17 in 19 memory 18 episodic 19 memory we hypothesized that higher levels of omega - 3 fatty acids , vitamin d , and physical activity relate to cortical sparing , whereas higher levels of cholesterol , systolic blood pressure , and body mass index ( bmi ) relate to increased atrophy in the adult lifespan . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 hypothesized 1 we 2 hypothesized 2 hypothesized 3 that 3 that 16 and 3 that 19 relate 4 higher 5 levels 5 levels 6 of 5 levels 16 and 6 of 7 omega 7 omega 11 acids 7 omega 13 vitamin 8 - 11 acids 9 3 11 acids 10 fatty 11 acids 11 acids 12 , 12 , 13 vitamin 13 vitamin 14 d 13 vitamin 15 , 15 , 16 and 16 and 18 activity 16 and 19 relate 17 physical 18 activity 19 relate 20 to 19 relate 24 whereas 20 to 22 sparing 21 cortical 22 sparing 23 , 24 whereas 24 whereas 26 levels 24 whereas 41 relate 24 whereas 49 . 25 higher 26 levels 26 levels 27 of 26 levels 41 relate 27 of 34 and 28 cholesterol 29 , 29 , 32 pressure 29 , 34 and 30 systolic 31 blood 31 blood 32 pressure 33 , 34 and 34 and 37 index 34 and 39 bmi 35 body 37 index 36 mass 37 index 38 ( 39 bmi 39 bmi 40 ) 41 relate 42 to 41 relate 45 in 42 to 44 atrophy 43 increased 44 atrophy 45 in 48 lifespan 46 the 48 lifespan 47 adult 48 lifespan longitudinal measures of cortical thickness were derived from magnetic resonance imaging scans acquired ( mean interval 3.6 years ) from 203 healthy persons aged 23 - 87 years . 0 ###LEFT-WALL### 2 measures 0 ###LEFT-WALL### 7 derived 0 ###LEFT-WALL### 29 . 1 longitudinal 2 measures 2 measures 3 of 2 measures 6 were 3 of 5 thickness 4 cortical 5 thickness 6 were 7 derived 7 derived 8 from 7 derived 20 from 8 from 10 resonance 9 magnetic 10 resonance 10 resonance 11 imaging 10 resonance 12 scans 10 resonance 13 acquired 10 resonance 18 years 11 imaging 12 scans 14 ( 18 years 15 mean 18 years 16 interval 18 years 17 3.6 18 years 18 years 19 ) 20 from 28 years 21 203 28 years 22 healthy 28 years 23 persons 24 aged 24 aged 26 - 25 23 26 - 26 - 27 87 27 87 28 years [at] follow - up , measures of bmi , blood pressure , and physical activity were obtained . 0 ###LEFT-WALL### 2 follow 0 ###LEFT-WALL### 5 , 0 ###LEFT-WALL### 18 . 2 follow 4 up 3 - 4 up 4 up 5 , 5 , 6 measures 5 , 17 obtained 6 measures 7 of 6 measures 16 were 7 of 13 and 8 bmi 9 , 9 , 11 pressure 9 , 13 and 10 blood 11 pressure 12 , 13 and 13 and 15 activity 14 physical 15 activity 16 were 17 obtained blood levels of docosahexaenoic acid , eicosapentaenoic acid , vitamin d , and cholesterol were measured in a subsample ( n = 92 ) . 0 ###LEFT-WALL### 2 levels 0 ###LEFT-WALL### 15 were 0 ###LEFT-WALL### 25 . 1 blood 2 levels 2 levels 3 of 2 levels 15 were 3 of 13 and 4 docosahexaenoic 8 acid 5 acid 6 , 5 acid 8 acid 7 eicosapentaenoic 8 acid 8 acid 9 , 9 , 10 vitamin 9 , 13 and 10 vitamin 11 d 12 , 13 and 13 and 14 cholesterol 15 were 16 measured 16 measured 17 in 17 in 19 subsample 18 a 19 subsample 19 subsample 22 = 20 ( 22 = 21 n 22 = 22 = 23 92 22 = 24 ) effects were tested in cortical [surface] - based analyses , with sex , age , follow - up interval , and the interactions between each included [as] covariates . 0 ###LEFT-WALL### 1 effects 0 ###LEFT-WALL### 3 tested 0 ###LEFT-WALL### 15 , 1 effects 2 were 2 were 3 tested 3 tested 4 in 4 in 9 analyses 5 cortical 7 - 5 cortical 9 analyses 8 based 9 analyses 9 analyses 11 with 9 analyses 14 age 10 , 11 with 11 with 12 sex 11 with 13 , 13 , 14 age 14 age 15 , 15 , 16 follow 15 , 17 - 17 - 19 interval 17 - 21 and 17 - 29 . 18 up 19 interval 20 , 21 and 21 and 23 interactions 21 and 26 included 22 the 23 interactions 23 interactions 24 between 23 interactions 26 included 24 between 25 each 26 included 28 covariates higher levels of docosahexaenoic acid , vitamin d , and physical activity related to cortical sparing . 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 17 . 1 higher 2 levels 2 levels 3 of 2 levels 6 , 3 of 5 acid 4 docosahexaenoic 5 acid 6 , 7 vitamin 6 , 10 and 7 vitamin 8 d 9 , 10 and 10 and 12 activity 10 and 13 related 11 physical 12 activity 13 related 14 to 14 to 16 sparing 15 cortical 16 sparing higher cholesterol and bmi related to increased cortical thinning . 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 10 . 1 higher 2 cholesterol 2 cholesterol 3 and 3 and 4 bmi 3 and 5 related 5 related 6 to 6 to 9 thinning 7 increased 9 thinning 8 cortical 9 thinning effects were independent , did not interact with age , and the cholesterol effect was restricted to males . 0 ###LEFT-WALL### 1 effects 0 ###LEFT-WALL### 4 , 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 19 . 1 effects 4 , 2 were 3 independent 2 were 4 , 4 , 5 did 5 did 6 not 5 did 7 interact 7 interact 8 with 8 with 9 age 10 , 11 and 11 and 14 effect 11 and 16 restricted 12 the 14 effect 13 cholesterol 14 effect 14 effect 15 was 15 was 16 restricted 16 restricted 17 to 17 to 18 males eicosapentaenoic acid and blood pressure showed no effects . 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 6 showed 0 ###LEFT-WALL### 9 . 1 eicosapentaenoic 2 acid 2 acid 3 and 3 and 5 pressure 3 and 6 showed 4 blood 5 pressure 6 showed 8 effects 7 no 8 effects the observed effects [show] promise for potential factors to reduce cortical atrophy in normal aging . 0 ###LEFT-WALL### 3 effects 0 ###LEFT-WALL### 5 promise 0 ###LEFT-WALL### 16 . 1 the 3 effects 2 observed 3 effects 3 effects 5 promise 5 promise 6 for 5 promise 9 to 5 promise 10 reduce 6 for 8 factors 7 potential 8 factors 9 to 10 reduce 10 reduce 12 atrophy 10 reduce 13 in 11 cortical 12 atrophy 13 in 15 aging 14 normal 15 aging the health care needs of elderly people were influenced by their heterogeneity . 0 ###LEFT-WALL### 4 needs 0 ###LEFT-WALL### 9 influenced 0 ###LEFT-WALL### 13 . 1 the 4 needs 2 health 4 needs 3 care 4 needs 4 needs 5 of 4 needs 8 were 5 of 7 people 6 elderly 7 people 8 were 9 influenced 9 influenced 10 by 10 by 12 heterogeneity 11 their 12 heterogeneity this study aimed to identify the health latent classes of elderly people by using latent class analysis to deal with heterogeneity and examine their socio - demographic characteristics . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 aimed 0 ###LEFT-WALL### 29 . 1 this 2 study 2 study 3 aimed 3 aimed 4 to 3 aimed 13 by 4 to 5 identify 5 identify 9 classes 6 the 9 classes 7 health 9 classes 8 latent 9 classes 9 classes 10 of 10 of 12 people 11 elderly 12 people 13 by 14 using 14 using 17 analysis 14 using 18 to 14 using 22 and 15 latent 16 class 16 class 17 analysis 18 to 22 and 19 deal 20 with 19 deal 22 and 20 with 21 heterogeneity 22 and 23 examine 22 and 28 characteristics 24 their 28 characteristics 25 socio 26 - 25 socio 28 characteristics 27 demographic 28 characteristics data came from the 2005 national health interview survey ( nhis ) in taiwan . 0 ###LEFT-WALL### 1 data 0 ###LEFT-WALL### 2 came 0 ###LEFT-WALL### 15 . 1 data 2 came 2 came 3 from 2 came 13 in 3 from 11 nhis 4 the 5 2005 5 2005 11 nhis 6 national 7 health 7 health 8 interview 8 interview 9 survey 9 survey 11 nhis 10 ( 11 nhis 11 nhis 12 ) 13 in 14 taiwan in total , 2449 elderly individuals with available health indicators were examined in latent class analysis ( lca ) , and 2217 elderly community - dwellings with complete socio - demographic data were analyzed by multinomial logistic regression . 0 ###LEFT-WALL### 32 data 0 ###LEFT-WALL### 34 analyzed 0 ###LEFT-WALL### 39 . 1 in 2 total 2 total 3 , 2 total 32 data 4 2449 6 individuals 5 elderly 6 individuals 6 individuals 7 with 6 individuals 12 examined 6 individuals 21 and 7 with 9 health 8 available 9 health 9 health 10 indicators 9 health 11 were 10 indicators 11 were 12 examined 13 in 13 in 16 analysis 14 latent 15 class 15 class 16 analysis 16 analysis 18 lca 17 ( 18 lca 18 lca 19 ) 20 , 21 and 21 and 24 community 21 and 26 dwellings 21 and 32 data 22 2217 24 community 23 elderly 24 community 25 - 26 dwellings 26 dwellings 27 with 26 dwellings 30 - 27 with 29 socio 28 complete 29 socio 31 demographic 32 data 32 data 33 were 33 were 34 analyzed 34 analyzed 35 by 35 by 38 regression 36 multinomial 38 regression 37 logistic 38 regression four health latent classes [were] identified which included 1066 ( 43.5 % ) people in the high comorbidity ( hc ) , 152 ( 6.2 % ) in the functional impairment ( fi ) , 252 ( 10.3 % ) in the frail ( fr ) , and 979 ( 40.0 % [ )(in the relatively healthy ( rh ) group . 0 ###LEFT-WALL### 4 classes 0 ###LEFT-WALL### 14 people 0 ###LEFT-WALL### 48 and 0 ###LEFT-WALL### 62 . 1 four 4 classes 2 health 4 classes 3 latent 4 classes 4 classes 6 identified 4 classes 7 which 4 classes 8 included 4 classes 12 % 4 classes 14 people 7 which 8 included 8 included 9 1066 10 ( 12 % 11 43.5 12 % 12 % 13 ) 14 people 15 in 14 people 28 in 14 people 31 impairment 14 people 41 in 15 in 20 hc 16 the 20 hc 17 high 18 comorbidity 18 comorbidity 20 hc 19 ( 20 hc 20 hc 21 ) 20 hc 23 152 22 , 23 152 23 152 26 % 23 152 27 ) 24 ( 26 % 25 6.2 26 % 26 % 27 ) 28 in 30 functional 29 the 30 functional 31 impairment 33 fi 31 impairment 36 252 32 ( 33 fi 33 fi 34 ) 35 , 36 252 36 252 39 % 36 252 40 ) 37 ( 39 % 38 10.3 39 % 39 % 40 ) 41 in 43 frail 42 the 43 frail 43 frail 45 fr 44 ( 45 fr 45 fr 46 ) 47 , 48 and 48 and 49 979 48 and 61 group 49 979 52 % 49 979 61 group 50 ( 52 % 51 40.0 52 % 52 % 54 )(in 52 % 60 ) 54 )(in 59 rh 55 the 59 rh 56 relatively 57 healthy 57 healthy 59 rh 58 ( 59 rh multinomial logistic regressions revealed socio - demographic characteristics among health classes . 0 ###LEFT-WALL### 3 regressions 0 ###LEFT-WALL### 4 revealed 0 ###LEFT-WALL### 12 . 1 multinomial 3 regressions 2 logistic 3 regressions 3 regressions 4 revealed 4 revealed 8 characteristics 4 revealed 9 among 5 socio 6 - 5 socio 8 characteristics 7 demographic 8 characteristics 9 among 11 classes 10 health 11 classes the variables associated with [an] increased likelihood of being in the fr group were age , female , and living with families . 0 ###LEFT-WALL### 2 variables 0 ###LEFT-WALL### 14 were 0 ###LEFT-WALL### 23 . 1 the 2 variables 2 variables 3 associated 2 variables 4 with 2 variables 8 of 2 variables 14 were 4 with 7 likelihood 6 increased 7 likelihood 8 of 9 being 9 being 10 in 10 in 13 group 11 the 13 group 12 fr 13 group 14 were 19 and 15 age 16 , 16 , 17 female 16 , 19 and 18 , 19 and 19 and 20 living 19 and 21 with 21 with 22 families they were also correlated to ethnicity and educations . 0 ###LEFT-WALL### 1 they 0 ###LEFT-WALL### 2 were 0 ###LEFT-WALL### 9 . 1 they 2 were 2 were 7 and 3 also 4 correlated 4 correlated 5 to 4 correlated 7 and 5 to 6 ethnicity 7 and 8 educations apart from age and gender , the functional impairment group was less likely to be ethnicity of hakka , more likely to live with others than were the rh group . 0 ###LEFT-WALL### 10 group 0 ###LEFT-WALL### 11 was 0 ###LEFT-WALL### 19 , 0 ###LEFT-WALL### 31 . 1 apart 2 from 2 from 4 and 2 from 6 , 2 from 10 group 3 age 4 and 4 and 5 gender 7 the 10 group 8 functional 9 impairment 9 impairment 10 group 10 group 11 was 11 was 13 likely 12 less 13 likely 13 likely 14 to 13 likely 15 be 14 to 15 be 15 be 16 ethnicity 16 ethnicity 17 of 17 of 18 hakka 19 , 22 to 19 , 23 live 19 , 26 than 20 more 21 likely 21 likely 22 to 22 to 23 live 23 live 24 with 24 with 25 others 26 than 27 were 26 than 30 group 27 were 29 rh 27 were 30 group 28 the 29 rh the hc group tended to be younger , with higher educations , and more likely to live in urban area than the functional impairment group . 0 ###LEFT-WALL### 3 group 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 26 . 1 the 3 group 2 hc 3 group 3 group 13 and 4 tended 5 to 4 tended 6 be 4 tended 13 and 5 to 6 be 6 be 7 younger 7 younger 9 with 8 , 9 with 9 with 11 educations 9 with 12 , 10 higher 11 educations 12 , 13 and 13 and 16 to 13 and 25 group 14 more 15 likely 15 likely 16 to 16 to 17 live 17 live 18 in 17 live 21 than 18 in 20 area 19 urban 20 area 21 than 24 impairment 22 the 24 impairment 23 functional 24 impairment the correlations between health classes and socio - demographic factors were discussed . 0 ###LEFT-WALL### 2 correlations 0 ###LEFT-WALL### 12 discussed 0 ###LEFT-WALL### 13 . 1 the 2 correlations 2 correlations 3 between 2 correlations 11 were 3 between 6 and 4 health 5 classes 5 classes 6 and 6 and 10 factors 7 socio 8 - 7 socio 10 factors 9 demographic 10 factors 11 were 12 discussed the health status of elderly people includes a variety of health indicators . 0 ###LEFT-WALL### 3 status 0 ###LEFT-WALL### 7 includes 0 ###LEFT-WALL### 13 . 1 the 3 status 2 health 3 status 3 status 4 of 3 status 7 includes 4 of 6 people 5 elderly 6 people 7 includes 9 variety 8 a 9 variety 9 variety 10 of 10 of 12 indicators 11 health 12 indicators a person [-] centered approach is critical to identify the health heterogeneity of elderly people and manage their care needs by targeting differential aging . 0 ###LEFT-WALL### 5 approach 0 ###LEFT-WALL### 16 and 0 ###LEFT-WALL### 25 . 1 a 5 approach 2 person 4 centered 4 centered 5 approach 5 approach 6 is 6 is 7 critical 7 critical 8 to 8 to 16 and 9 identify 12 heterogeneity 9 identify 16 and 10 the 12 heterogeneity 11 health 12 heterogeneity 12 heterogeneity 13 of 13 of 15 people 14 elderly 15 people 16 and 17 manage 17 manage 20 needs 17 manage 21 by 18 their 20 needs 19 care 20 needs 21 by 22 targeting 22 targeting 24 aging 23 differential 24 aging von willebrand [factor] a ( vwa ) domains are versatile protein interaction domains with n and [c] termini in close proximity placing spatial constraints on overall protein structure . 0 ###LEFT-WALL### 8 domains 0 ###LEFT-WALL### 9 are 0 ###LEFT-WALL### 29 . 1 von 2 willebrand 2 willebrand 4 a 2 willebrand 6 vwa 5 ( 6 vwa 6 vwa 7 ) 6 vwa 8 domains 8 domains 9 are 9 are 13 domains 10 versatile 11 protein 11 protein 12 interaction 12 interaction 13 domains 13 domains 14 with 13 domains 22 placing 14 with 16 and 15 n 16 and 16 and 18 termini 16 and 19 in 19 in 21 proximity 20 close 21 proximity 22 placing 24 constraints 23 spatial 24 constraints 24 constraints 25 on 25 on 28 structure 26 overall 27 protein 27 protein 28 structure the 1.2 å crystal structures of a collagen [vi] vwa domain and a disease - causing point mutant show c - terminal extensions that place the n and [c] termini at opposite ends . 0 ###LEFT-WALL### 2 1.2 0 ###LEFT-WALL### 3 å 0 ###LEFT-WALL### 21 - 0 ###LEFT-WALL### 34 . 1 the 2 1.2 2 1.2 3 å 3 å 5 structures 4 crystal 5 structures 5 structures 6 of 5 structures 16 causing 6 of 12 and 7 a 11 domain 8 collagen 11 domain 10 vwa 11 domain 11 domain 12 and 12 and 14 disease 13 a 14 disease 15 - 16 causing 16 causing 19 show 16 causing 21 - 17 point 19 show 18 mutant 19 show 19 show 20 c 21 - 23 extensions 22 terminal 23 extensions 23 extensions 24 that 23 extensions 25 place 24 that 25 place 25 place 28 and 25 place 31 at 26 the 28 and 27 n 28 and 28 and 30 termini 31 at 33 ends 32 opposite 33 ends this allows a " [beads] - [on] - a [-] string " arrangement of multiple vwa domains as observed for ten n - terminal domains of [the] collagen vi α3 chain . 0 ###LEFT-WALL### 1 this 0 ###LEFT-WALL### 2 allows 0 ###LEFT-WALL### 23 - 1 this 2 allows 2 allows 11 string 2 allows 13 arrangement 2 allows 20 for 3 a 4 " 3 a 6 - 6 - 8 - 6 - 11 string 8 - 9 a 8 - 11 string 11 string 12 " 13 arrangement 14 of 13 arrangement 19 observed 14 of 17 domains 15 multiple 17 domains 16 vwa 17 domains 18 as 19 observed 20 for 22 n 21 ten 22 n 23 - 25 domains 23 - 30 α3 23 - 32 . 24 terminal 25 domains 25 domains 26 of 25 domains 30 α3 26 of 28 collagen 28 collagen 29 vi 30 α3 31 chain the extension is linked to the core domain by a salt bridge and two hydrophobic patches . 0 ###LEFT-WALL### 2 extension 0 ###LEFT-WALL### 4 linked 0 ###LEFT-WALL### 17 . 1 the 2 extension 2 extension 3 is 3 is 4 linked 4 linked 5 to 4 linked 9 by 5 to 8 domain 6 the 8 domain 7 core 8 domain 9 by 13 and 10 a 11 salt 10 a 12 bridge 11 salt 12 bridge 12 bridge 13 and 13 and 16 patches 14 two 16 patches 15 hydrophobic 16 patches comparison of the wild - type and a muscular dystrophy - associated mutant structure identifies a potential perturbation of a protein interaction interface and indeed , the secretion of mutant collagen vi tetramers is affected . 0 ###LEFT-WALL### 1 comparison 0 ###LEFT-WALL### 15 identifies 0 ###LEFT-WALL### 24 and 0 ###LEFT-WALL### 36 . 1 comparison 2 of 1 comparison 15 identifies 2 of 7 and 3 the 6 type 4 wild 5 - 4 wild 6 type 6 type 7 and 7 and 14 structure 8 a 9 muscular 8 a 14 structure 9 muscular 14 structure 10 dystrophy 11 - 10 dystrophy 14 structure 12 associated 14 structure 13 mutant 14 structure 15 identifies 18 perturbation 16 a 17 potential 16 a 18 perturbation 17 potential 18 perturbation 18 perturbation 19 of 19 of 23 interface 20 a 21 protein 20 a 23 interface 21 protein 22 interaction 22 interaction 23 interface 24 and 28 secretion 24 and 35 affected 25 indeed 26 , 25 indeed 28 secretion 27 the 28 secretion 28 secretion 29 of 28 secretion 34 is 29 of 31 collagen 30 mutant 31 collagen 31 collagen 32 vi 31 collagen 33 tetramers 32 vi 33 tetramers 34 is 35 affected homology modeling is used to locate a number of disease - associated mutations and analyze their structural impact , which will allow mechanistic analysis of collagen - vi - associated muscular dystrophy phenotypes . 0 ###LEFT-WALL### 2 modeling 0 ###LEFT-WALL### 4 used 0 ###LEFT-WALL### 11 - 0 ###LEFT-WALL### 34 . 1 homology 2 modeling 2 modeling 3 is 3 is 4 used 4 used 5 to 5 to 6 locate 6 locate 10 disease 7 a 8 number 8 number 9 of 8 number 10 disease 9 of 10 disease 11 - 14 and 11 - 19 , 11 - 33 phenotypes 12 associated 13 mutations 12 associated 14 and 14 and 15 analyze 15 analyze 18 impact 16 their 18 impact 17 structural 18 impact 19 , 20 which 19 , 22 allow 20 which 21 will 21 will 22 allow 22 allow 24 analysis 23 mechanistic 24 analysis 24 analysis 25 of 24 analysis 30 associated 24 analysis 32 dystrophy 24 analysis 33 phenotypes 25 of 26 collagen 26 collagen 28 vi 27 - 28 vi 28 vi 29 - 31 muscular 32 dystrophy 32 dystrophy 33 phenotypes traumatic brain injury ( tbi ) is characterized by an abrupt blow or exchange of force against the head and can be categorized as mild , moderate , and severe . 0 ###LEFT-WALL### 3 injury 0 ###LEFT-WALL### 23 categorized 0 ###LEFT-WALL### 31 . 1 traumatic 3 injury 2 brain 3 injury 3 injury 5 tbi 3 injury 20 and 4 ( 5 tbi 5 tbi 6 ) 7 is 8 characterized 7 is 20 and 8 characterized 9 by 9 by 13 or 10 an 11 abrupt 10 an 12 blow 11 abrupt 12 blow 12 blow 13 or 13 or 14 exchange 13 or 15 of 13 or 17 against 15 of 16 force 17 against 19 head 18 the 19 head 20 and 21 can 21 can 22 be 22 be 23 categorized 23 categorized 24 as 24 as 29 and 25 mild 26 , 26 , 27 moderate 26 , 29 and 28 , 29 and 29 and 30 severe the secondary cell death after tbi displays ischemic - [like] patterns including neuroinflammation . 0 ###LEFT-WALL### 4 death 0 ###LEFT-WALL### 7 displays 0 ###LEFT-WALL### 14 . 1 the 4 death 2 secondary 3 cell 3 cell 4 death 4 death 5 after 4 death 7 displays 5 after 6 tbi 7 displays 11 patterns 8 ischemic 9 - 8 ischemic 11 patterns 11 patterns 12 including 12 including 13 neuroinflammation the scavenger receptor cluster of differentiation ( cd ) [36] is a lipid - associated protein capable of transducing intracellular signals to promote inflammatory mechanisms within different cell types . 0 ###LEFT-WALL### 4 cluster 0 ###LEFT-WALL### 11 is 1 the 4 cluster 2 scavenger 3 receptor 3 receptor 4 cluster 4 cluster 5 of 4 cluster 11 is 5 of 6 differentiation 6 differentiation 8 cd 7 ( 8 cd 8 cd 9 ) 11 is 13 lipid 12 a 13 lipid 13 lipid 16 protein 14 - 16 protein 15 associated 16 protein 16 protein 17 capable 16 protein 30 . 17 capable 18 of 18 of 19 transducing 19 transducing 21 signals 19 transducing 22 to 19 transducing 26 within 20 intracellular 21 signals 22 to 23 promote 23 promote 25 mechanisms 24 inflammatory 25 mechanisms 26 within 29 types 27 different 28 cell 28 cell 29 types expression and activation of cd36 is closely related to dyslipidemia secondary to diabetes . 0 ###LEFT-WALL### 1 expression 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 14 . 2 and 3 activation 2 and 8 related 3 activation 4 of 3 activation 6 is 4 of 5 cd36 6 is 7 closely 6 is 8 related 8 related 9 to 9 to 10 dyslipidemia 10 dyslipidemia 11 secondary 11 secondary 12 to 12 to 13 diabetes diabetes mellitus ( dm ) has been documented as a co - morbidity factor in tbi , in that patients with a history of diabetes present with more severe brain damage and slower recovery from tbi than [non] - diabetic patients . 0 ###LEFT-WALL### 2 mellitus 0 ###LEFT-WALL### 8 documented 0 ###LEFT-WALL### 39 - 1 diabetes 2 mellitus 2 mellitus 4 dm 2 mellitus 6 has 3 ( 4 dm 4 dm 5 ) 6 has 7 been 7 been 8 documented 8 documented 9 as 8 documented 19 that 9 as 14 factor 10 a 14 factor 11 co 12 - 11 co 13 morbidity 13 morbidity 14 factor 14 factor 15 in 15 in 16 tbi 17 , 19 that 18 in 19 that 19 that 20 patients 19 that 30 brain 19 that 39 - 20 patients 21 with 20 patients 26 present 20 patients 30 brain 21 with 23 history 22 a 23 history 23 history 24 of 24 of 25 diabetes 26 present 27 with 27 with 28 more 27 with 29 severe 30 brain 34 recovery 30 brain 35 from 30 brain 37 than 31 damage 32 and 32 and 33 slower 32 and 34 recovery 35 from 36 tbi 39 - 41 patients 39 - 42 . 40 diabetic 41 patients indeed , a strict regulation of blood serum glucose by the use of insulin promotes a better outcome for tbi patients . 0 ###LEFT-WALL### 5 regulation 0 ###LEFT-WALL### 15 promotes 0 ###LEFT-WALL### 22 . 1 indeed 2 , 1 indeed 5 regulation 3 a 4 strict 3 a 5 regulation 4 strict 5 regulation 5 regulation 6 of 5 regulation 15 promotes 6 of 9 glucose 7 blood 9 glucose 8 serum 9 glucose 9 glucose 10 by 10 by 12 use 11 the 12 use 12 use 13 of 13 of 14 insulin 15 promotes 18 outcome 16 a 18 outcome 17 better 18 outcome 18 outcome 19 for 19 for 21 patients 20 tbi 21 patients based on these recent findings , we now advance the hypothesis that cd36 via dm insulin [-] associated pathways is closely involved in tbi chronic pathology . 0 ###LEFT-WALL### 7 we 0 ###LEFT-WALL### 9 advance 0 ###LEFT-WALL### 27 . 1 based 2 on 1 based 6 , 1 based 7 we 2 on 5 findings 3 these 5 findings 4 recent 5 findings 7 we 9 advance 8 now 9 advance 9 advance 11 hypothesis 10 the 11 hypothesis 11 hypothesis 12 that 12 that 13 cd36 12 that 22 involved 13 cd36 14 via 13 cd36 20 is 14 via 19 pathways 15 dm 18 associated 16 insulin 18 associated 18 associated 19 pathways 20 is 21 closely 20 is 22 involved 22 involved 23 in 23 in 26 pathology 24 tbi 26 pathology 25 chronic 26 pathology a premutation [(] [pm] [ )(expansion [(] 55 - 200 cgg [ )(in the fragile [x] mental retardation gene 1 causes elevated messenger rna and reduced fragile [x] mental retardation gene 1 protein . 0 ###LEFT-WALL### 11 cgg 0 ###LEFT-WALL### 21 causes 0 ###LEFT-WALL### 34 . 1 a 11 cgg 2 premutation 11 cgg 6 )(expansion 11 cgg 8 55 9 - 9 - 10 200 9 - 11 cgg 11 cgg 13 )(in 11 cgg 21 causes 13 )(in 19 gene 14 the 19 gene 15 fragile 18 retardation 17 mental 18 retardation 18 retardation 19 gene 19 gene 20 1 21 causes 33 protein 22 elevated 23 messenger 23 messenger 33 protein 24 rna 25 and 25 and 31 gene 25 and 33 protein 26 reduced 30 retardation 27 fragile 30 retardation 29 mental 30 retardation 30 retardation 31 gene 31 gene 32 1 young [pm] carriers can develop characteristic physical features and mild cognitive disabilities . 0 ###LEFT-WALL### 3 carriers 0 ###LEFT-WALL### 5 develop 0 ###LEFT-WALL### 13 . 1 young 3 carriers 3 carriers 4 can 4 can 5 develop 5 develop 9 and 6 characteristic 8 features 7 physical 8 features 8 features 9 and 9 and 12 disabilities 10 mild 12 disabilities 11 cognitive 12 disabilities in addition , individuals [with] [pm] , particularly male carriers , are at high risk to develop fragile [x] - associated tremor/ataxia [syndrome] ( fxtas ) with aging . 0 ###LEFT-WALL### 4 individuals 0 ###LEFT-WALL### 12 are 0 ###LEFT-WALL### 29 . 1 in 2 addition 1 in 3 , 1 in 4 individuals 4 individuals 10 carriers 4 individuals 12 are 7 , 10 carriers 8 particularly 9 male 9 male 10 carriers 10 carriers 11 , 12 are 13 at 12 are 16 to 12 are 27 with 13 at 15 risk 14 high 15 risk 16 to 17 develop 17 develop 22 tremor/ataxia 18 fragile 20 - 18 fragile 22 tremor/ataxia 21 associated 22 tremor/ataxia 22 tremor/ataxia 25 fxtas 24 ( 25 fxtas 25 fxtas 26 ) 27 with 28 aging human postmortem fxtas brains show extensive white matter disease in the cerebellum and the presence of intranuclear inclusions throughout the brain , although their etiologic significance is unknown . 0 ###LEFT-WALL### 4 brains 0 ###LEFT-WALL### 5 show 1 human 2 postmortem 2 postmortem 4 brains 3 fxtas 4 brains 4 brains 5 show 5 show 8 matter 5 show 9 disease 5 show 13 and 5 show 19 throughout 5 show 23 although 6 extensive 8 matter 7 white 8 matter 9 disease 10 in 10 in 12 cerebellum 11 the 12 cerebellum 13 and 15 presence 14 the 15 presence 15 presence 16 of 16 of 18 inclusions 17 intranuclear 18 inclusions 19 throughout 21 brain 20 the 21 brain 22 , 23 although 23 although 26 significance 23 although 27 is 23 although 29 . 24 their 26 significance 25 etiologic 26 significance 26 significance 27 is 27 is 28 unknown in the current work , expression levels of the metabotropic glutamate ( glu ) receptor 5 and the glu transporter excitatory amino acid transporter 1 , examined by reverse transcription polymerase chain reaction and western blot analyses , were found to be reduced in the postmortem cerebellum of [pm] carriers with fxtas compared with age matched controls , with higher cgg repeat number having greater reductions in both proteins . 0 ###LEFT-WALL### 4 work 0 ###LEFT-WALL### 5 , 1 in 3 current 1 in 4 work 2 the 3 current 5 , 17 and 6 expression 7 levels 7 levels 8 of 7 levels 17 and 8 of 15 receptor 9 the 15 receptor 10 metabotropic 15 receptor 11 glutamate 13 glu 11 glutamate 14 ) 11 glutamate 15 receptor 12 ( 13 glu 13 glu 14 ) 15 receptor 16 5 17 and 24 transporter 17 and 26 , 17 and 27 examined 18 the 24 transporter 19 glu 20 transporter 20 transporter 24 transporter 21 excitatory 23 acid 22 amino 23 acid 23 acid 24 transporter 24 transporter 25 1 27 examined 28 by 27 examined 34 and 27 examined 38 , 28 by 30 transcription 29 reverse 30 transcription 31 polymerase 32 chain 32 chain 33 reaction 33 reaction 34 and 34 and 35 western 34 and 38 , 36 blot 37 analyses 36 blot 38 , 38 , 39 were 38 , 41 to 39 were 40 found 41 to 42 be 42 be 43 reduced 43 reduced 44 in 43 reduced 51 with 44 in 47 cerebellum 45 the 47 cerebellum 46 postmortem 47 cerebellum 47 cerebellum 48 of 48 of 50 carriers 51 with 52 fxtas 52 fxtas 53 compared 52 fxtas 54 with 52 fxtas 59 with 54 with 57 controls 55 age 56 matched 56 matched 57 controls 58 , 59 with 59 with 66 reductions 59 with 67 in 59 with 70 . 60 higher 62 repeat 61 cgg 62 repeat 62 repeat 63 number 63 number 66 reductions 64 having 66 reductions 65 greater 66 reductions 67 in 69 proteins 68 both 69 proteins [these] data suggests a dysregulation of glu signaling in [pm] carriers , which would likely contribute to the development and severity of fxtas . 0 ###LEFT-WALL### 2 data 0 ###LEFT-WALL### 3 suggests 0 ###LEFT-WALL### 12 , 0 ###LEFT-WALL### 24 . 2 data 3 suggests 3 suggests 5 dysregulation 3 suggests 9 in 4 a 5 dysregulation 5 dysregulation 6 of 6 of 7 glu 7 glu 8 signaling 9 in 11 carriers 12 , 13 which 12 , 16 contribute 13 which 14 would 14 would 16 contribute 15 likely 16 contribute 16 contribute 17 to 17 to 20 and 18 the 19 development 19 development 20 and 20 and 21 severity 20 and 22 of 22 of 23 fxtas none objectives : to analyse the influence of irradiation time , aging before bleaching , and bleaching technique ( home bleaching [vs] [.] [in] - office bleaching [ )(on the amount of elutable substances from modern nano - hybrid resin - based composites ( rbcs ) . 0 ###LEFT-WALL### 1 none 0 ###LEFT-WALL### 5 analyse 0 ###LEFT-WALL### 11 , 1 none 2 objectives 1 none 4 to 1 none 5 analyse 2 objectives 3 : 3 : 4 to 5 analyse 7 influence 6 the 7 influence 7 influence 8 of 8 of 10 time 9 irradiation 10 time 11 , 16 and 12 aging 13 before 12 aging 16 and 13 before 14 bleaching 15 , 16 and 16 and 18 technique 16 and 25 - 17 bleaching 18 technique 19 ( 25 - 20 home 21 bleaching 20 home 25 - 25 - 27 bleaching 26 office 27 bleaching 27 bleaching 29 )(on 29 )(on 31 amount 30 the 31 amount 31 amount 32 of 32 of 34 substances 33 elutable 34 substances 34 substances 35 from 35 from 40 resin 36 modern 39 hybrid 37 nano 38 - 37 nano 39 hybrid 39 hybrid 40 resin 40 resin 43 composites 41 - 43 composites 42 based 43 composites 43 composites 45 rbcs 43 composites 47 . 44 ( 45 rbcs 45 rbcs 46 ) methods : specimens ( n=5 [ )(of three nano - hybrid rbcs ( venus ( [®] [ )(diamond , tetric evoceram ( [®] [ )(and filtek ™ supreme xte ) were irradiated for 5 , 10 , 20 and 40 s . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 3 specimens 2 : 10 - 3 specimens 5 n=5 4 ( 5 n=5 5 n=5 7 )(of 5 n=5 10 - 7 )(of 9 nano 8 three 9 nano 10 - 12 rbcs 10 - 19 , 11 hybrid 12 rbcs 12 rbcs 14 venus 13 ( 14 venus 14 venus 18 )(diamond 14 venus 19 , 15 ( 18 )(diamond 18 )(diamond 19 , 19 , 25 )(and 20 tetric 21 evoceram 21 evoceram 25 )(and 22 ( 25 )(and 25 )(and 29 xte 25 )(and 30 ) 25 )(and 31 were 26 filtek 27 ™ 27 ™ 29 xte 28 supreme 29 xte 31 were 32 irradiated 32 irradiated 33 for 33 for 34 5 34 5 36 10 34 5 41 s 35 , 36 10 36 10 37 , 37 , 41 s 38 20 39 and 39 and 40 40 39 and 41 s 41 s 42 . the degree of conversion [(] [dc] [ )(was measured in real - time with fourier [transform] infrared spectroscopy ( ftir ) . 0 ###LEFT-WALL### 4 conversion 0 ###LEFT-WALL### 8 )(was 0 ###LEFT-WALL### 22 . 1 the 2 degree 2 degree 3 of 2 degree 4 conversion 3 of 4 conversion 4 conversion 8 )(was 8 )(was 9 measured 9 measured 10 in 9 measured 14 with 10 in 13 time 11 real 12 - 11 real 13 time 14 with 15 fourier 14 with 18 spectroscopy 17 infrared 18 spectroscopy 18 spectroscopy 20 ftir 19 ( 20 ftir 20 ftir 21 ) specimens were bleached either directly after irradiation or after aging [(] 1.5 or 6 month in distilled water at 37 °c [ )(with opalescence [(] [®] [ )(pf15 % for 6 h [(] simulation of home bleaching [ )(or pf35 % for 0.5 h [(] simulation of in [-] office bleaching [ )(and incubated [in] ethanol/water ( 3:1 [ )(at 37 °c for 7 d . 1 specimens 2 were 2 were 3 bleached 3 bleached 4 either 3 bleached 5 directly 3 bleached 8 or 6 after 7 irradiation 6 after 8 or 8 or 9 after 9 after 10 aging 10 aging 15 month 10 aging 16 in 12 1.5 13 or 13 or 14 6 13 or 15 month 16 in 18 water 17 distilled 18 water 18 water 19 at 18 water 23 )(with 18 water 30 for 19 at 21 °c 20 37 21 °c 23 )(with 29 % 24 opalescence 28 )(pf15 28 )(pf15 29 % 30 for 34 simulation 31 6 32 h 32 h 34 simulation 34 simulation 35 of 34 simulation 42 for 35 of 41 % 36 home 37 bleaching 36 home 39 )(or 39 )(or 40 pf35 39 )(or 41 % 42 for 53 )(and 43 0.5 44 h 44 h 46 simulation 46 simulation 47 of 46 simulation 51 bleaching 46 simulation 53 )(and 47 of 50 office 48 in 50 office 53 )(and 56 ethanol/water 53 )(and 58 3:1 54 incubated 56 ethanol/water 57 ( 58 3:1 58 3:1 60 )(at 58 3:1 66 . 60 )(at 62 °c 61 37 62 °c 62 °c 63 for 63 for 65 d 64 7 65 d the eluates were analyzed by gas chromatography/mass spectrometry . 0 ###LEFT-WALL### 2 eluates 0 ###LEFT-WALL### 4 analyzed 0 ###LEFT-WALL### 9 . 1 the 2 eluates 2 eluates 3 were 3 were 4 analyzed 4 analyzed 5 by 5 by 8 spectrometry 6 gas 8 spectrometry 7 chromatography/mass 8 spectrometry unbleached specimens at the [above] mentioned irradiation times were used as controls . 0 ###LEFT-WALL### 2 specimens 0 ###LEFT-WALL### 10 used 0 ###LEFT-WALL### 13 . 1 unbleached 2 specimens 2 specimens 3 at 2 specimens 9 were 3 at 8 times 4 the 8 times 6 mentioned 7 irradiation 7 irradiation 8 times 9 were 10 used 10 used 11 as 11 as 12 controls results : bleaching increases the amount of elutable substances . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 3 bleaching 2 : 4 increases 2 : 10 . 3 bleaching 4 increases 4 increases 6 amount 5 the 6 amount 6 amount 7 of 7 of 9 substances 8 elutable 9 substances this amount is generally stronger [influenced] by aging than by polymerization time or concentration of the gel . 0 ###LEFT-WALL### 2 amount 0 ###LEFT-WALL### 3 is 0 ###LEFT-WALL### 18 . 1 this 2 amount 2 amount 3 is 3 is 4 generally 3 is 5 stronger 5 stronger 7 by 7 by 8 aging 8 aging 9 than 9 than 10 by 10 by 13 or 11 polymerization 12 time 12 time 13 or 13 or 14 concentration 13 or 15 of 15 of 17 gel 16 the 17 gel diethoyxdimethylsilane was found in all eluates from bleached specimens , but not in the control groups . 0 ###LEFT-WALL### 1 diethoyxdimethylsilane 0 ###LEFT-WALL### 3 found 0 ###LEFT-WALL### 17 . 1 diethoyxdimethylsilane 2 was 2 was 3 found 3 found 4 in 4 in 6 eluates 5 all 6 eluates 6 eluates 11 but 7 from 9 specimens 7 from 11 but 8 bleached 9 specimens 10 , 11 but 11 but 12 not 11 but 13 in 13 in 16 groups 14 the 16 groups 15 control 16 groups this substance may be formed by oxidation of 3 - methacryloxy - propyltrimethoxysilane , indicating that the bond between inorganic filler and organic matrix might be weakened after bleaching . 0 ###LEFT-WALL### 4 be 0 ###LEFT-WALL### 30 . 1 this 2 substance 2 substance 3 may 3 may 4 be 4 be 5 formed 5 formed 6 by 5 formed 28 after 6 by 7 oxidation 7 oxidation 8 of 7 oxidation 15 indicating 8 of 9 3 9 3 13 propyltrimethoxysilane 10 - 13 propyltrimethoxysilane 11 methacryloxy 12 - 11 methacryloxy 13 propyltrimethoxysilane 13 propyltrimethoxysilane 14 , 15 indicating 16 that 16 that 22 and 16 that 27 weakened 17 the 18 bond 18 bond 19 between 18 bond 22 and 19 between 21 filler 20 inorganic 21 filler 22 and 24 matrix 22 and 25 might 23 organic 24 matrix 25 might 26 be 26 be 27 weakened 28 after 29 bleaching significance : bleaching gels might alter the physical properties of resin - based composites , especially at low irradiation times and fresh placed restorations . 0 ###LEFT-WALL### 1 significance 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 25 . 2 : 3 bleaching 2 : 6 alter 3 bleaching 4 gels 3 bleaching 5 might 5 might 6 alter 6 alter 9 properties 6 alter 16 especially 7 the 9 properties 8 physical 9 properties 9 properties 10 of 10 of 11 resin 11 resin 14 composites 12 - 14 composites 13 based 14 composites 14 composites 15 , 16 especially 17 at 17 at 21 and 18 low 19 irradiation 19 irradiation 20 times 20 times 21 and 21 and 24 restorations 22 fresh 24 restorations 23 placed 24 restorations epithelial - mesenchymal transition ( emt ) is an important developmental process hijacked by cancer cells for their dissemination . 0 ###LEFT-WALL### 1 epithelial 0 ###LEFT-WALL### 8 is 0 ###LEFT-WALL### 20 . 1 epithelial 4 transition 1 epithelial 8 is 2 - 4 transition 3 mesenchymal 4 transition 4 transition 6 emt 4 transition 7 ) 5 ( 6 emt 6 emt 7 ) 8 is 12 process 9 an 10 important 9 an 12 process 10 important 12 process 11 developmental 12 process 12 process 13 hijacked 13 hijacked 14 by 14 by 16 cells 15 cancer 16 cells 16 cells 17 for 17 for 19 dissemination 18 their 19 dissemination here , we show that exo70 , a component of the exocyst complex , undergoes isoform switching mediated by esrp1 , a pre - mrna splicing factor that regulates emt . 1 here 2 , 1 here 3 we 3 we 4 show 4 show 5 that 5 that 6 exo70 5 that 15 undergoes 6 exo70 9 component 6 exo70 15 undergoes 7 , 9 component 8 a 9 component 9 component 10 of 9 component 14 , 10 of 13 complex 11 the 13 complex 12 exocyst 13 complex 15 undergoes 16 isoform 15 undergoes 19 by 16 isoform 17 switching 16 isoform 18 mediated 19 by 20 esrp1 20 esrp1 27 factor 21 , 27 factor 22 a 23 pre 22 a 27 factor 23 pre 24 - 23 pre 25 mrna 25 mrna 27 factor 26 splicing 27 factor 27 factor 28 that 27 factor 29 regulates 27 factor 31 . 28 that 29 regulates 29 regulates 30 emt expression of the epithelial isoform of exo70 affects the levels of key emt transcriptional regulators such as snail and zeb2 and is sufficient to drive the transition [to] epithelial [phenotypes] . 0 ###LEFT-WALL### 1 expression 0 ###LEFT-WALL### 21 and 0 ###LEFT-WALL### 31 . 1 expression 2 of 1 expression 21 and 2 of 5 isoform 3 the 5 isoform 4 epithelial 5 isoform 5 isoform 6 of 6 of 7 exo70 8 affects 10 levels 8 affects 17 as 8 affects 21 and 9 the 10 levels 10 levels 11 of 11 of 15 regulators 12 key 15 regulators 13 emt 15 regulators 14 transcriptional 15 regulators 16 such 17 as 17 as 19 and 18 snail 19 and 19 and 20 zeb2 21 and 22 is 22 is 23 sufficient 23 sufficient 24 to 23 sufficient 25 drive 24 to 25 drive 25 drive 27 transition 25 drive 29 epithelial 26 the 27 transition differential exo70 isoform expression in human tumors correlates with cancer progression , and increased expression of the epithelial isoform of exo70 inhibits tumor metastasis in mice . 0 ###LEFT-WALL### 4 expression 0 ###LEFT-WALL### 8 correlates 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 27 . 1 differential 4 expression 2 exo70 4 expression 3 isoform 4 expression 4 expression 5 in 4 expression 8 correlates 5 in 7 tumors 6 human 7 tumors 8 correlates 9 with 9 with 11 progression 10 cancer 11 progression 12 , 13 and 13 and 15 expression 13 and 22 inhibits 14 increased 15 expression 15 expression 16 of 15 expression 22 inhibits 16 of 19 isoform 17 the 19 isoform 18 epithelial 19 isoform 19 isoform 20 of 20 of 21 exo70 22 inhibits 24 metastasis 22 inhibits 25 in 23 tumor 24 metastasis 25 in 26 mice at the molecular level , the mesenchymal - but not the epithelial - isoform of exo70 interacts with the arp2/3 complex and [stimulates] actin polymerization [for] tumor invasion . 0 ###LEFT-WALL### 14 isoform 0 ###LEFT-WALL### 17 interacts 0 ###LEFT-WALL### 29 . 1 at 4 level 1 at 14 isoform 2 the 4 level 3 molecular 4 level 4 level 7 mesenchymal 5 , 7 mesenchymal 6 the 7 mesenchymal 7 mesenchymal 8 - 9 but 10 not 9 but 14 isoform 11 the 14 isoform 12 epithelial 13 - 12 epithelial 14 isoform 14 isoform 15 of 14 isoform 17 interacts 15 of 16 exo70 17 interacts 18 with 18 with 22 and 19 the 21 complex 20 arp2/3 21 complex 21 complex 22 and 22 and 28 invasion 24 actin 28 invasion 25 polymerization 28 invasion 27 tumor 28 invasion our findings provide a mechanism by which the exocyst function and actin dynamics are modulated for emt and tumor invasion . 0 ###LEFT-WALL### 2 findings 0 ###LEFT-WALL### 3 provide 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 21 . 1 our 2 findings 2 findings 3 provide 3 provide 5 mechanism 4 a 5 mechanism 5 mechanism 6 by 6 by 7 which 6 by 9 exocyst 6 by 10 function 8 the 9 exocyst 9 exocyst 10 function 11 and 13 dynamics 11 and 15 modulated 12 actin 13 dynamics 13 dynamics 14 are 14 are 15 modulated 15 modulated 16 for 16 for 18 and 17 emt 18 and 18 and 20 invasion 19 tumor 20 invasion research in gerontology has demonstrated mixed effects of social support on cognitive decline [and] dementia : social support has been shown to be protective in some studies , but not in others . 0 ###LEFT-WALL### 1 research 0 ###LEFT-WALL### 4 has 0 ###LEFT-WALL### 16 : 1 research 2 in 1 research 4 has 2 in 3 gerontology 4 has 7 effects 5 demonstrated 7 effects 6 mixed 7 effects 7 effects 8 of 8 of 10 support 9 social 10 support 10 support 11 on 11 on 15 dementia 12 cognitive 13 decline 13 decline 15 dementia 16 : 18 support 16 : 21 shown 16 : 33 . 17 social 18 support 18 support 19 has 19 has 20 been 20 been 21 shown 21 shown 22 to 22 to 23 be 23 be 24 protective 24 protective 29 but 25 in 27 studies 25 in 29 but 26 some 27 studies 28 , 29 but 29 but 30 not 29 but 31 in 31 in 32 others moreover , little is known about the underlying mechanisms between social support and cognitive functioning . 0 ###LEFT-WALL### 3 little 0 ###LEFT-WALL### 5 known 0 ###LEFT-WALL### 16 . 1 moreover 2 , 1 moreover 3 little 3 little 4 is 4 is 5 known 5 known 6 about 5 known 10 between 6 about 9 mechanisms 7 the 9 mechanisms 8 underlying 9 mechanisms 10 between 13 and 11 social 12 support 12 support 13 and 13 and 14 cognitive 13 and 15 functioning we investigate one of the possible mechanisms , and argue that subjective appraisals [rather] than received amounts of social support affect cognitive functioning . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 15 than 0 ###LEFT-WALL### 24 . 1 we 9 and 2 investigate 3 one 2 investigate 9 and 3 one 4 of 4 of 7 mechanisms 5 the 7 mechanisms 6 possible 7 mechanisms 8 , 9 and 9 and 10 argue 9 and 13 appraisals 11 that 12 subjective 12 subjective 13 appraisals 15 than 17 amounts 15 than 21 affect 16 received 17 amounts 17 amounts 18 of 17 amounts 21 affect 18 of 20 support 19 social 20 support 21 affect 23 functioning 22 cognitive 23 functioning loneliness is seen as an unpleasant experience that occurs when a person 's network of relationships is felt to be deficient in some important way . 0 ###LEFT-WALL### 1 loneliness 0 ###LEFT-WALL### 3 seen 0 ###LEFT-WALL### 26 . 1 loneliness 2 is 2 is 3 seen 3 seen 4 as 4 as 7 experience 5 an 6 unpleasant 5 an 7 experience 6 unpleasant 7 experience 7 experience 8 that 7 experience 9 occurs 8 that 9 occurs 9 occurs 10 when 9 occurs 19 to 9 occurs 20 be 10 when 14 network 10 when 17 is 11 a 12 person 12 person 13 's 13 's 14 network 14 network 15 of 14 network 17 is 15 of 16 relationships 17 is 18 felt 19 to 20 be 20 be 21 deficient 21 deficient 22 in 22 in 25 way 23 some 25 way 24 important 25 way as such [,] loneliness describes the extent to which someone 's needs are not being met and thus provides a subjective assessment of support quality . 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 26 . 1 as 4 loneliness 1 as 17 and 2 such 4 loneliness 5 describes 7 extent 5 describes 17 and 6 the 7 extent 7 extent 8 to 8 to 9 which 8 to 12 needs 8 to 16 met 10 someone 11 's 11 's 12 needs 12 needs 13 are 13 are 14 not 13 are 15 being 15 being 16 met 17 and 19 provides 18 thus 19 provides 19 provides 22 assessment 20 a 22 assessment 21 subjective 22 assessment 22 assessment 23 of 23 of 25 quality 24 support 25 quality we expect that receiving instrumental and emotional support reduces loneliness , which in turn preserves cognitive functioning . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 expect 0 ###LEFT-WALL### 11 , 0 ###LEFT-WALL### 18 . 1 we 2 expect 2 expect 3 that 3 that 4 receiving 3 that 9 reduces 4 receiving 8 support 4 receiving 9 reduces 5 instrumental 6 and 6 and 7 emotional 6 and 8 support 9 reduces 10 loneliness 11 , 12 which 11 , 15 preserves 12 which 15 preserves 13 in 14 turn 14 turn 15 preserves 15 preserves 17 functioning 16 cognitive 17 functioning data are from the longitudinal aging study amsterdam ( lasa ) and include 2255 dutch participants aged 55 - 85 over a period of six years . 0 ###LEFT-WALL### 1 data 0 ###LEFT-WALL### 2 are 0 ###LEFT-WALL### 27 . 1 data 2 are 2 are 3 from 2 are 17 aged 3 from 12 and 4 the 10 lasa 5 longitudinal 6 aging 6 aging 7 study 7 study 8 amsterdam 8 amsterdam 10 lasa 9 ( 10 lasa 10 lasa 11 ) 10 lasa 12 and 12 and 16 participants 13 include 16 participants 14 2255 16 participants 15 dutch 16 participants 17 aged 19 - 17 aged 21 over 18 55 19 - 19 - 20 85 21 over 23 period 22 a 23 period 23 period 24 of 24 of 26 years 25 six 26 years respondents were measured every three years . 0 ###LEFT-WALL### 1 respondents 0 ###LEFT-WALL### 2 were 0 ###LEFT-WALL### 7 . 1 respondents 2 were 2 were 3 measured 3 measured 4 every 4 every 6 years 5 three 6 years cognitive functioning was assessed with the mini - mental state examination ( mmse ) , the coding task , and the raven 's coloured progressive matrices . 0 ###LEFT-WALL### 1 cognitive 0 ###LEFT-WALL### 4 assessed 0 ###LEFT-WALL### 15 , 0 ###LEFT-WALL### 27 . 1 cognitive 2 functioning 1 cognitive 3 was 3 was 4 assessed 4 assessed 5 with 5 with 7 mini 6 the 7 mini 7 mini 11 examination 8 - 11 examination 9 mental 10 state 10 state 11 examination 11 examination 13 mmse 11 examination 14 ) 12 ( 13 mmse 13 mmse 14 ) 15 , 20 and 16 the 18 task 17 coding 18 task 18 task 20 and 19 , 20 and 20 and 26 matrices 21 the 22 raven 22 raven 23 's 23 's 26 matrices 24 coloured 25 progressive 25 progressive 26 matrices the analytical approach comprised latent growth mediation models . 0 ###LEFT-WALL### 3 approach 0 ###LEFT-WALL### 4 comprised 0 ###LEFT-WALL### 9 . 1 the 3 approach 2 analytical 3 approach 3 approach 4 comprised 4 comprised 8 models 5 latent 6 growth 6 growth 8 models 7 mediation 8 models frequent emotional support related to reduced feelings of loneliness and better cognitive functioning . 0 ###LEFT-WALL### 1 frequent 0 ###LEFT-WALL### 14 . 1 frequent 3 support 1 frequent 5 to 2 emotional 3 support 3 support 4 related 5 to 10 and 6 reduced 7 feelings 6 reduced 10 and 7 feelings 8 of 8 of 9 loneliness 10 and 11 better 11 better 13 functioning 12 cognitive 13 functioning increases in emotional support also directly enhanced cognitive performance . 0 ###LEFT-WALL### 1 increases 0 ###LEFT-WALL### 7 enhanced 0 ###LEFT-WALL### 10 . 1 increases 2 in 1 increases 7 enhanced 2 in 4 support 3 emotional 4 support 5 also 7 enhanced 6 directly 7 enhanced 7 enhanced 9 performance 8 cognitive 9 performance the protective effect of emotional support was [strongest] amongst adults aged 65 years and older . 0 ###LEFT-WALL### 3 effect 0 ###LEFT-WALL### 7 was 0 ###LEFT-WALL### 16 . 1 the 3 effect 2 protective 3 effect 3 effect 4 of 3 effect 7 was 4 of 6 support 5 emotional 6 support 7 was 9 amongst 9 amongst 10 adults 10 adults 11 aged 11 aged 14 and 12 65 13 years 13 years 14 and 14 and 15 older increase in instrumental support did not [buffer] [cognitive] decline , instead there were indications [for] faster [decline] . 0 ###LEFT-WALL### 1 increase 0 ###LEFT-WALL### 9 decline 0 ###LEFT-WALL### 10 , 0 ###LEFT-WALL### 18 . 1 increase 2 in 1 increase 5 did 2 in 4 support 3 instrumental 4 support 5 did 6 not 5 did 9 decline 10 , 12 there 10 , 13 were 11 instead 12 there 12 there 13 were 13 were 14 indications 13 were 16 faster after ruling out the possibility of reversed causation , we conclude that emotional support relationships are a more powerful protector of cognitive decline than instrumental support relationships . 0 ###LEFT-WALL### 10 we 0 ###LEFT-WALL### 11 conclude 0 ###LEFT-WALL### 28 . 1 after 2 ruling 1 after 9 , 1 after 10 we 2 ruling 3 out 2 ruling 5 possibility 4 the 5 possibility 5 possibility 6 of 6 of 8 causation 7 reversed 8 causation 10 we 11 conclude 11 conclude 12 that 12 that 15 relationships 12 that 16 are 13 emotional 14 support 14 support 15 relationships 15 relationships 16 are 16 are 20 protector 17 a 20 protector 18 more 19 powerful 19 powerful 20 protector 20 protector 21 of 21 of 27 relationships 22 cognitive 23 decline 23 decline 27 relationships 24 than 25 instrumental 25 instrumental 26 support 26 support 27 relationships this paper explores whether educational attainment has a cognitive reserve capacity in elder life . 0 ###LEFT-WALL### 2 paper 0 ###LEFT-WALL### 3 explores 0 ###LEFT-WALL### 15 . 1 this 2 paper 2 paper 3 explores 3 explores 4 whether 4 whether 6 attainment 4 whether 7 has 5 educational 6 attainment 6 attainment 7 has 7 has 11 capacity 7 has 12 in 8 a 9 cognitive 8 a 11 capacity 9 cognitive 10 reserve 10 reserve 11 capacity 12 in 14 life 13 elder 14 life using pilot data from the china health and retirement longitudinal study ( charls ) , we examined the impact of education on cognitive abilities at old ages . 0 ###LEFT-WALL### 16 we 0 ###LEFT-WALL### 17 examined 0 ###LEFT-WALL### 28 . 1 using 3 data 1 using 4 from 1 using 15 , 1 using 16 we 2 pilot 3 data 4 from 8 and 5 the 7 health 6 china 7 health 7 health 8 and 8 and 13 charls 9 retirement 10 longitudinal 10 longitudinal 11 study 11 study 13 charls 12 ( 13 charls 13 charls 14 ) 16 we 17 examined 17 examined 19 impact 17 examined 22 on 17 examined 25 at 18 the 19 impact 19 impact 20 of 20 of 21 education 22 on 24 abilities 23 cognitive 24 abilities 25 at 27 ages 26 old 27 ages ols results showed that respondents who completed primary school obtained 18.2 percent higher scores on cognitive tests than those who did not . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 showed 0 ###LEFT-WALL### 23 . 1 ols 2 results 2 results 3 showed 3 showed 4 that 4 that 5 respondents 4 that 10 obtained 5 respondents 6 who 5 respondents 7 completed 5 respondents 10 obtained 6 who 7 completed 7 completed 9 school 8 primary 9 school 10 obtained 14 scores 10 obtained 15 on 10 obtained 18 than 11 18.2 14 scores 12 percent 14 scores 13 higher 14 scores 15 on 17 tests 16 cognitive 17 tests 18 than 19 those 19 those 20 who 19 those 21 did 20 who 21 did 21 did 22 not we then constructed an instrumental variable ( iv ) by leveraging china 's great famine of 1959 - 1961 as a natural experiment to estimate the causal effect of education on cognition . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 constructed 0 ###LEFT-WALL### 33 . 1 we 3 constructed 2 then 3 constructed 3 constructed 6 variable 3 constructed 10 by 3 constructed 24 to 3 constructed 31 on 4 an 5 instrumental 4 an 6 variable 5 instrumental 6 variable 6 variable 8 iv 7 ( 8 iv 8 iv 9 ) 10 by 11 leveraging 11 leveraging 15 famine 11 leveraging 20 as 12 china 13 's 13 's 15 famine 14 great 15 famine 15 famine 16 of 16 of 18 - 17 1959 18 - 18 - 19 1961 20 as 23 experiment 21 a 22 natural 21 a 23 experiment 22 natural 23 experiment 24 to 25 estimate 25 estimate 28 effect 26 the 28 effect 27 causal 28 effect 28 effect 29 of 29 of 30 education 31 on 32 cognition two - stage least squares ( 2sls ) results provided sound evidence that completing primary school significantly increases cognition scores , especially in episode memory , by almost 20 percent on average . 0 ###LEFT-WALL### 1 two 0 ###LEFT-WALL### 2 - 2 - 3 stage 2 - 33 . 3 stage 4 least 3 stage 5 squares 3 stage 23 in 3 stage 27 by 3 stage 32 average 5 squares 9 results 6 ( 9 results 7 2sls 8 ) 7 2sls 9 results 9 results 10 provided 9 results 12 evidence 9 results 20 scores 9 results 21 , 11 sound 12 evidence 12 evidence 13 that 12 evidence 20 scores 13 that 14 completing 13 that 18 increases 14 completing 16 school 14 completing 17 significantly 14 completing 18 increases 15 primary 16 school 18 increases 19 cognition 21 , 22 especially 21 , 23 in 23 in 25 memory 23 in 26 , 24 episode 25 memory 27 by 30 percent 28 almost 29 20 29 20 30 percent 31 on 32 average moreover , regression discontinuity ( rd ) analysis provides further evidence for the causal interpretation , and shows that the effects are different for the different measures of cognition we explored . 0 ###LEFT-WALL### 8 analysis 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 32 . 1 moreover 2 , 1 moreover 8 analysis 3 regression 4 discontinuity 4 discontinuity 6 rd 5 ( 6 rd 6 rd 7 ) 6 rd 8 analysis 8 analysis 17 and 9 provides 11 evidence 9 provides 12 for 9 provides 17 and 10 further 11 evidence 12 for 15 interpretation 13 the 15 interpretation 14 causal 15 interpretation 16 , 17 and 17 and 18 shows 17 and 24 for 18 shows 19 that 19 that 21 effects 19 that 22 are 20 the 21 effects 21 effects 22 are 22 are 23 different 24 for 27 measures 25 the 27 measures 26 different 27 measures 27 measures 28 of 27 measures 30 we 27 measures 31 explored 28 of 29 cognition 30 we 31 explored our results also show that the great famine can result in long - term health consequences through the pathway of losing educational opportunities other than [through] the pathway of nutrition deprivation . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 4 show 0 ###LEFT-WALL### 32 . 1 our 2 results 2 results 4 show 3 also 4 show 4 show 5 that 5 that 8 famine 5 that 10 result 6 the 8 famine 7 great 8 famine 8 famine 9 can 9 can 10 result 10 result 11 in 11 in 16 consequences 12 long 13 - 12 long 14 term 14 term 16 consequences 15 health 16 consequences 16 consequences 17 through 16 consequences 20 of 17 through 19 pathway 18 the 19 pathway 20 of 21 losing 21 losing 23 opportunities 21 losing 25 than 22 educational 23 opportunities 24 other 25 than 25 than 28 pathway 27 the 28 pathway 28 pathway 29 of 29 of 31 deprivation 30 nutrition 31 deprivation despite the scarcity of high quality cancer registries and lack of reliable mortality data , it is clear that human papillomavirus ( hpv ) - associated diseases , particularly cervical cancer , are major causes of morbidity and mortality [in] sub - saharan africa ( ssa ) . 0 ###LEFT-WALL### 16 it 0 ###LEFT-WALL### 18 clear 0 ###LEFT-WALL### 32 , 0 ###LEFT-WALL### 33 are 0 ###LEFT-WALL### 48 . 1 despite 3 scarcity 1 despite 16 it 2 the 3 scarcity 3 scarcity 4 of 4 of 9 and 5 high 8 registries 6 quality 7 cancer 7 cancer 8 registries 8 registries 9 and 9 and 10 lack 11 of 14 data 11 of 15 , 11 of 16 it 12 reliable 13 mortality 13 mortality 14 data 16 it 17 is 17 is 18 clear 18 clear 21 papillomavirus 19 that 21 papillomavirus 20 human 21 papillomavirus 21 papillomavirus 23 hpv 21 papillomavirus 27 diseases 22 ( 23 hpv 23 hpv 24 ) 25 - 27 diseases 26 associated 27 diseases 27 diseases 31 cancer 27 diseases 32 , 28 , 31 cancer 29 particularly 30 cervical 30 cervical 31 cancer 31 cancer 32 , 32 , 33 are 33 are 35 causes 33 are 44 africa 34 major 35 causes 35 causes 36 of 36 of 38 and 37 morbidity 38 and 38 and 41 sub 38 and 42 - 39 mortality 41 sub 43 saharan 44 africa 44 africa 46 ssa 45 ( 46 ssa 46 ssa 47 ) cervical cancer incidence rates in ssa are the highest in the world and the disease is the most common cause of cancer death among women in the region . 0 ###LEFT-WALL### 4 rates 0 ###LEFT-WALL### 7 are 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 29 . 1 cervical 2 cancer 2 cancer 3 incidence 3 incidence 4 rates 4 rates 5 in 4 rates 7 are 5 in 6 ssa 7 are 9 highest 8 the 9 highest 9 highest 10 in 10 in 12 world 11 the 12 world 13 and 15 disease 13 and 16 is 14 the 15 disease 15 disease 16 is 16 is 18 most 16 is 19 common 17 the 18 most 19 common 20 cause 19 common 24 among 20 cause 21 of 21 of 23 death 22 cancer 23 death 24 among 25 women 25 women 26 in 26 in 28 region 27 the 28 region the high incidence of cervical cancer is a consequence of the inability of most countries to either initiate or sustain cervical cancer prevention services . 0 ###LEFT-WALL### 3 incidence 0 ###LEFT-WALL### 7 is 0 ###LEFT-WALL### 25 . 1 the 3 incidence 2 high 3 incidence 3 incidence 4 of 3 incidence 7 is 4 of 6 cancer 5 cervical 6 cancer 7 is 9 consequence 7 is 16 to 8 a 9 consequence 9 consequence 10 of 10 of 12 inability 11 the 12 inability 12 inability 13 of 13 of 15 countries 14 most 15 countries 16 to 19 or 17 either 18 initiate 18 initiate 19 or 19 or 20 sustain 20 sustain 24 services 21 cervical 22 cancer 22 cancer 24 services 23 prevention 24 services in addition , it appears that the prevalence of hpv in women with normal cytology is higher than in more developed areas of the world , at an average of 24 % . 0 ###LEFT-WALL### 4 it 0 ###LEFT-WALL### 5 appears 1 in 2 addition 1 in 3 , 1 in 4 it 4 it 5 appears 5 appears 6 that 6 that 8 prevalence 6 that 16 is 7 the 8 prevalence 8 prevalence 9 of 8 prevalence 16 is 9 of 10 hpv 10 hpv 11 in 11 in 12 women 12 women 13 with 13 with 15 cytology 14 normal 15 cytology 16 is 17 higher 17 higher 18 than 18 than 19 in 19 in 22 areas 20 more 21 developed 21 developed 22 areas 22 areas 23 of 23 of 25 world 24 the 25 world 25 world 27 at 26 , 27 at 27 at 29 average 27 at 33 . 28 an 29 average 29 average 30 of 30 of 32 % 31 24 32 % there is , however , significant regional variation in ssa , with the highest incidence of hpv infection and cervical cancer found in eastern and western africa . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 11 , 0 ###LEFT-WALL### 28 . 1 there 2 is 2 is 4 however 2 is 8 variation 3 , 4 however 4 however 5 , 6 significant 8 variation 7 regional 8 variation 8 variation 9 in 9 in 10 ssa 11 , 19 and 11 , 22 found 12 with 15 incidence 12 with 19 and 13 the 14 highest 13 the 15 incidence 15 incidence 16 of 16 of 17 hpv 18 infection 19 and 19 and 21 cancer 19 and 22 found 20 cervical 21 cancer 22 found 23 in 22 found 25 and 24 eastern 25 and 25 and 27 africa 26 western 27 africa it is expected that , due to aging and growth of the population , but also to lack of access to appropriate prevention services and the concomitant human immunodeficiency virus ( hiv )/acquired immunodeficiency [syndrome] ( aids ) epidemic , cervical cancer incidence and mortality rates in ssa will rise over the next 20 years . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 3 expected 0 ###LEFT-WALL### 56 . 1 it 2 is 2 is 3 expected 3 expected 4 that 4 that 44 and 4 that 50 rise 5 , 7 to 6 due 7 to 7 to 9 and 7 to 14 , 7 to 44 and 8 aging 9 and 9 and 10 growth 10 growth 11 of 11 of 13 population 12 the 13 population 15 but 16 also 15 but 44 and 17 to 18 lack 17 to 44 and 18 lack 19 of 19 of 20 access 21 to 25 and 21 to 38 ) 21 to 44 and 22 appropriate 23 prevention 23 prevention 24 services 24 services 25 and 25 and 30 virus 25 and 34 immunodeficiency 26 the 30 virus 27 concomitant 29 immunodeficiency 28 human 29 immunodeficiency 29 immunodeficiency 30 virus 31 ( 34 immunodeficiency 32 hiv 34 immunodeficiency 33 )/acquired 34 immunodeficiency 34 immunodeficiency 37 aids 34 immunodeficiency 38 ) 36 ( 37 aids 37 aids 38 ) 39 epidemic 40 , 40 , 43 incidence 40 , 44 and 41 cervical 42 cancer 42 cancer 43 incidence 44 and 46 rates 44 and 47 in 44 and 50 rise 45 mortality 46 rates 47 in 49 will 48 ssa 49 will 50 rise 51 over 51 over 55 years 52 the 53 next 52 the 54 20 54 20 55 years hpv16 and 18 are the most common [genotypes] in cervical cancer in ssa , although other carcinogenic hpv types , such as hpv45 [and] 35 , are also relatively more frequent [compared] with other world regions . 0 ###LEFT-WALL### 1 hpv16 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 31 frequent 0 ###LEFT-WALL### 37 . 2 and 3 18 2 and 4 are 3 18 4 are 4 are 6 most 4 are 15 although 5 the 6 most 6 most 7 common 7 common 9 in 7 common 12 in 9 in 11 cancer 10 cervical 11 cancer 12 in 13 ssa 14 , 15 although 15 although 18 hpv 16 other 18 hpv 17 carcinogenic 18 hpv 18 hpv 19 types 18 hpv 27 are 18 hpv 31 frequent 19 types 22 as 19 types 27 are 20 , 22 as 21 such 22 as 22 as 23 hpv45 22 as 26 , 23 hpv45 25 35 27 are 28 also 27 are 30 more 29 relatively 30 more 31 frequent 33 with 31 frequent 36 regions 33 with 35 world 34 other 35 world data on other hpv - related anogenital cancers including those of the vulva , vagina , anus , and penis , are limited . 0 ###LEFT-WALL### 1 data 0 ###LEFT-WALL### 23 limited 0 ###LEFT-WALL### 24 . 1 data 2 on 1 data 22 are 2 on 4 hpv 3 other 4 hpv 5 - 6 related 6 related 8 cancers 6 related 21 , 6 related 22 are 7 anogenital 8 cancers 8 cancers 9 including 9 including 19 and 10 those 11 of 10 those 14 , 11 of 13 vulva 12 the 13 vulva 14 , 15 vagina 14 , 16 , 16 , 17 anus 16 , 19 and 18 , 19 and 19 and 20 penis 22 are 23 limited genital warts are common and associated [with] hpv types 6 and 11 . 0 ###LEFT-WALL### 2 warts 0 ###LEFT-WALL### 3 are 0 ###LEFT-WALL### 5 and 0 ###LEFT-WALL### 13 . 1 genital 2 warts 2 warts 3 are 3 are 4 common 5 and 8 hpv 5 and 9 types 6 associated 8 hpv 8 hpv 9 types 9 types 11 and 10 6 11 and 11 and 12 11 hiv infection increases [incidence] and prevalence of all hpv - associated diseases . 0 ###LEFT-WALL### 5 and 0 ###LEFT-WALL### 10 - 1 hiv 3 increases 2 infection 3 increases 3 increases 5 and 5 and 6 prevalence 5 and 7 of 7 of 9 hpv 8 all 9 hpv 10 - 12 diseases 10 - 13 . 11 associated 12 diseases sociocultural determinants of hpv - related disease , as well as the impact of forces that result in social destabilization , demand further study . 0 ###LEFT-WALL### 2 determinants 0 ###LEFT-WALL### 22 demand 0 ###LEFT-WALL### 25 . 1 sociocultural 2 determinants 2 determinants 3 of 2 determinants 22 demand 3 of 4 hpv 5 - 6 related 6 related 7 disease 6 related 11 as 6 related 21 , 6 related 22 demand 8 , 11 as 9 as 10 well 10 well 11 as 11 as 13 impact 11 as 21 , 12 the 13 impact 13 impact 14 of 14 of 15 forces 15 forces 16 that 15 forces 17 result 16 that 17 result 17 result 18 in 18 in 20 destabilization 19 social 20 destabilization 22 demand 24 study 23 further 24 study strategies to reduce the excessive burden of hpv - related diseases in ssa include age - appropriate prophylactic hpv vaccination , cervical cancer prevention services for women of the reproductive ages , and control of hiv/aids . 0 ###LEFT-WALL### 1 strategies 0 ###LEFT-WALL### 14 include 0 ###LEFT-WALL### 21 , 0 ###LEFT-WALL### 37 . 1 strategies 2 to 1 strategies 3 reduce 1 strategies 14 include 2 to 3 reduce 3 reduce 6 burden 4 the 6 burden 5 excessive 6 burden 6 burden 7 of 7 of 8 hpv 9 - 10 related 10 related 11 diseases 10 related 12 in 10 related 14 include 12 in 13 ssa 14 include 15 age 15 age 20 vaccination 16 - 20 vaccination 17 appropriate 18 prophylactic 18 prophylactic 20 vaccination 19 hpv 20 vaccination 20 vaccination 21 , 21 , 33 and 22 cervical 23 cancer 23 cancer 25 services 24 prevention 25 services 25 services 26 for 25 services 33 and 26 for 27 women 27 women 28 of 28 of 31 ages 29 the 31 ages 30 reproductive 31 ages 32 , 33 and 33 and 34 control 33 and 35 of 35 of 36 hiv/aids this article forms part of a regional report entitled " comprehensive control of hpv infections and related diseases in the sub - saharan africa region " vaccine volume 31 , supplement 5 , 2013 . 0 ###LEFT-WALL### 2 article 0 ###LEFT-WALL### 3 forms 0 ###LEFT-WALL### 22 - 0 ###LEFT-WALL### 35 . 1 this 2 article 2 article 3 forms 3 forms 16 and 4 part 5 of 4 part 13 of 4 part 16 and 5 of 8 report 6 a 8 report 7 regional 8 report 8 report 9 entitled 9 entitled 10 " 9 entitled 12 control 11 comprehensive 12 control 13 of 15 infections 14 hpv 15 infections 16 and 18 diseases 16 and 19 in 17 related 18 diseases 19 in 21 sub 20 the 21 sub 22 - 28 volume 22 - 33 , 23 saharan 24 africa 24 africa 25 region 25 region 26 " 25 region 27 vaccine 27 vaccine 28 volume 28 volume 29 31 28 volume 31 supplement 30 , 31 supplement 31 supplement 32 5 31 supplement 33 , 33 , 34 2013 updates of the progress in the field are presented in a separate monograph entitled " comprehensive control of hpv infections and related diseases " vaccine volume 30 , supplement 5 , 2012 . 0 ###LEFT-WALL### 1 updates 0 ###LEFT-WALL### 9 presented 0 ###LEFT-WALL### 31 , 0 ###LEFT-WALL### 33 . 1 updates 2 of 1 updates 8 are 2 of 4 progress 3 the 4 progress 4 progress 5 in 5 in 7 field 6 the 7 field 8 are 9 presented 9 presented 10 in 10 in 13 monograph 11 a 12 separate 11 a 13 monograph 12 separate 13 monograph 13 monograph 14 entitled 13 monograph 18 of 14 entitled 15 " 14 entitled 17 control 16 comprehensive 17 control 18 of 26 volume 19 hpv 20 infections 20 infections 21 and 21 and 22 related 22 related 23 diseases 23 diseases 24 " 23 diseases 25 vaccine 25 vaccine 26 volume 26 volume 27 30 26 volume 29 supplement 28 , 29 supplement 29 supplement 30 5 29 supplement 31 , 31 , 32 2012 activation of the mammalian target of rapamycin ( mtor ) has been implicated in anticancer drug resistance , type 2 diabetes , and aging . 0 ###LEFT-WALL### 1 activation 0 ###LEFT-WALL### 13 implicated 0 ###LEFT-WALL### 18 , 0 ###LEFT-WALL### 25 . 1 activation 2 of 1 activation 6 of 1 activation 11 has 2 of 5 target 3 the 5 target 4 mammalian 5 target 6 of 7 rapamycin 7 rapamycin 9 mtor 8 ( 9 mtor 9 mtor 10 ) 11 has 12 been 12 been 13 implicated 13 implicated 14 in 14 in 17 resistance 15 anticancer 16 drug 16 drug 17 resistance 18 , 19 type 19 type 23 and 20 2 23 and 21 diabetes 23 and 22 , 23 and 23 and 24 aging here , we show that surface functionalization of polystyrene nanoparticles with amino groups ( ps - nh2 ) , but not with carboxyl groups ( ps - cooh ) , induces g2 cell [-] cycle arrest and inhibition of [proliferation] in three leukemia cell lines . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 show 0 ###LEFT-WALL### 46 . 1 here 2 , 1 here 3 we 3 we 4 show 4 show 5 that 5 that 7 functionalization 5 that 31 induces 6 surface 7 functionalization 7 functionalization 8 of 7 functionalization 20 but 7 functionalization 31 induces 8 of 10 nanoparticles 9 polystyrene 10 nanoparticles 11 with 13 groups 11 with 20 but 12 amino 13 groups 13 groups 15 ps 14 ( 15 ps 15 ps 17 nh2 15 ps 18 ) 16 - 17 nh2 17 nh2 18 ) 19 , 20 but 20 but 21 not 20 but 22 with 22 with 24 groups 23 carboxyl 24 groups 24 groups 28 cooh 25 ( 28 cooh 26 ps 28 cooh 27 - 28 cooh 28 cooh 29 ) 28 cooh 30 , 31 induces 37 and 32 g2 36 arrest 33 cell 35 cycle 35 cycle 36 arrest 36 arrest 37 and 37 and 38 inhibition 37 and 39 of 39 of 41 in 41 in 45 lines 42 three 45 lines 43 leukemia 45 lines 44 cell 45 lines besides , ps - nh2 [inhibit] angiogenesis and proliferation of leukemia cells xenografted onto the chick chorioallantoic membrane . 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 13 xenografted 0 ###LEFT-WALL### 19 . 1 besides 2 , 1 besides 8 and 2 , 3 ps 3 ps 4 - 3 ps 8 and 5 nh2 7 angiogenesis 7 angiogenesis 8 and 8 and 9 proliferation 8 and 10 of 8 and 13 xenografted 10 of 12 cells 11 leukemia 12 cells 13 xenografted 14 onto 13 xenografted 18 membrane 14 onto 16 chick 15 the 16 chick 17 chorioallantoic 18 membrane at the molecular level , ps - nh2 [inhibit] , whereas ps - cooh activate mtor signaling in leukemia cells . 0 ###LEFT-WALL### 14 cooh 0 ###LEFT-WALL### 15 activate 0 ###LEFT-WALL### 21 . 1 at 4 level 1 at 14 cooh 2 the 4 level 3 molecular 4 level 4 level 6 ps 5 , 6 ps 6 ps 8 nh2 6 ps 10 , 7 - 8 nh2 8 nh2 10 , 10 , 11 whereas 11 whereas 12 ps 11 whereas 13 - 11 whereas 14 cooh 14 cooh 15 activate 15 activate 16 mtor 15 activate 18 in 16 mtor 17 signaling 18 in 20 cells 19 leukemia 20 cells consistently , ps - nh2 block activation of the mtor downstream targets , akt and p70 ribosomal s6 kinase 1 , [and] induce overexpression of the cell - cycle regulator p21 ( cip1/waf1 ) and degradation of cyclin b1 . 0 ###LEFT-WALL### 15 and 0 ###LEFT-WALL### 23 induce 0 ###LEFT-WALL### 40 . 1 consistently 2 , 1 consistently 15 and 2 , 3 ps 3 ps 4 - 3 ps 15 and 5 nh2 7 activation 6 block 7 activation 7 activation 8 of 7 activation 13 , 8 of 12 targets 9 the 12 targets 10 mtor 12 targets 11 downstream 12 targets 13 , 14 akt 13 , 15 and 15 and 19 kinase 15 and 21 , 15 and 23 induce 16 p70 19 kinase 17 ribosomal 19 kinase 18 s6 19 kinase 19 kinase 20 1 23 induce 35 and 24 overexpression 25 of 24 overexpression 35 and 25 of 27 cell 26 the 27 cell 27 cell 31 p21 28 - 31 p21 29 cycle 31 p21 30 regulator 31 p21 31 p21 33 cip1/waf1 31 p21 34 ) 32 ( 33 cip1/waf1 33 cip1/waf1 34 ) 35 and 36 degradation 35 and 37 of 37 of 39 b1 38 cyclin 39 b1 after addition , both types of particles rapidly induce autophagy in leukemia cells . 0 ###LEFT-WALL### 7 particles 0 ###LEFT-WALL### 9 induce 0 ###LEFT-WALL### 14 . 1 after 2 addition 1 after 3 , 1 after 7 particles 4 both 5 types 5 types 6 of 5 types 7 particles 6 of 7 particles 7 particles 9 induce 8 rapidly 9 induce 9 induce 10 autophagy 9 induce 11 in 11 in 13 cells 12 leukemia 13 cells yet , only in ps - nh2 - treated cells , acidic vesicular organelles show elevated ph and impaired processing of procathepsin b . moreover , solely in ps - nh2 - treated cells , autophagy is followed by permeabilization of acidic vesicular organelles and induction of apoptosis . 0 ###LEFT-WALL### 1 yet 0 ###LEFT-WALL### 18 and 0 ###LEFT-WALL### 24 . 0 ###LEFT-WALL### 49 . 1 yet 14 organelles 2 , 3 only 2 , 4 in 4 in 5 ps 4 in 11 , 4 in 14 organelles 5 ps 7 nh2 6 - 7 nh2 7 nh2 10 cells 7 nh2 11 , 8 - 10 cells 9 treated 10 cells 10 cells 11 , 12 acidic 14 organelles 13 vesicular 14 organelles 14 organelles 18 and 15 show 17 ph 15 show 18 and 16 elevated 17 ph 18 and 19 impaired 18 and 20 processing 20 processing 21 of 21 of 22 procathepsin 22 procathepsin 23 b 24 . 36 autophagy 24 . 38 followed 25 moreover 26 , 25 moreover 36 autophagy 26 , 27 solely 26 , 28 in 28 in 29 ps 28 in 35 , 28 in 36 autophagy 29 ps 31 nh2 30 - 31 nh2 31 nh2 34 cells 31 nh2 35 , 32 - 34 cells 33 treated 34 cells 34 cells 35 , 36 autophagy 37 is 37 is 38 followed 38 followed 39 by 39 by 45 and 40 permeabilization 41 of 40 permeabilization 45 and 41 of 44 organelles 42 acidic 44 organelles 43 vesicular 44 organelles 45 and 46 induction 45 and 47 of 47 of 48 apoptosis by contrast , primary macrophages , which do not exhibit activated mtor signaling , proved relatively resistant to ps - nh2 - induced toxicity . 0 ###LEFT-WALL### 5 macrophages 0 ###LEFT-WALL### 23 induced 0 ###LEFT-WALL### 25 . 1 by 2 contrast 1 by 3 , 1 by 5 macrophages 4 primary 5 macrophages 5 macrophages 7 which 5 macrophages 15 proved 5 macrophages 23 induced 6 , 7 which 7 which 8 do 7 which 14 , 8 do 9 not 8 do 10 exhibit 10 exhibit 12 mtor 11 activated 12 mtor 12 mtor 13 signaling 14 , 15 proved 15 proved 17 resistant 15 proved 22 - 16 relatively 17 resistant 17 resistant 18 to 18 to 19 ps 19 ps 21 nh2 20 - 21 nh2 21 nh2 22 - 23 induced 24 toxicity these data indicate that functionalized nanoparticles can be used to control activation of mtor signaling pathways , and to influence proliferation [and] viability of malignant cells . 0 ###LEFT-WALL### 2 data 0 ###LEFT-WALL### 3 indicate 0 ###LEFT-WALL### 27 . 1 these 2 data 2 data 3 indicate 3 indicate 4 that 4 that 6 nanoparticles 4 that 18 and 5 functionalized 6 nanoparticles 6 nanoparticles 18 and 7 can 8 be 7 can 18 and 8 be 9 used 9 used 10 to 9 used 11 control 10 to 11 control 11 control 12 activation 12 activation 13 of 12 activation 15 signaling 13 of 14 mtor 15 signaling 16 pathways 17 , 18 and 18 and 19 to 18 and 20 influence 19 to 20 influence 20 influence 23 viability 21 proliferation 23 viability 23 viability 24 of 24 of 26 cells 25 malignant 26 cells we use data from respondents aged 60 years and above , collected during april 2009 in the rajshahi district of bangladesh , to examine whether high activeness , as captured by an aai or in sub [-] domains , can help reduce the risk of elder abuse . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 use 0 ###LEFT-WALL### 22 , 0 ###LEFT-WALL### 41 help 0 ###LEFT-WALL### 48 . 1 we 2 use 2 use 3 data 2 use 12 collected 3 data 9 and 4 from 8 years 4 from 9 and 5 respondents 6 aged 6 aged 8 years 7 60 8 years 9 and 10 above 11 , 12 collected 12 collected 13 during 12 collected 16 in 12 collected 22 , 13 during 14 april 14 april 15 2009 16 in 19 district 17 the 19 district 18 rajshahi 19 district 19 district 20 of 20 of 21 bangladesh 22 , 23 to 22 , 39 , 23 to 39 , 24 examine 25 whether 24 examine 27 activeness 24 examine 34 or 24 examine 39 , 25 whether 26 high 27 activeness 30 captured 28 , 30 captured 29 as 30 captured 31 by 33 aai 31 by 34 or 32 an 33 aai 34 or 35 in 35 in 38 domains 36 sub 38 domains 39 , 40 can 40 can 41 help 41 help 42 reduce 42 reduce 44 risk 43 the 44 risk 44 risk 45 of 45 of 47 abuse 46 elder 47 abuse the findings suggest that more than half of rural elderly [and] 14 percent [of] [urban] [elderly] were at some point abused [.] 0 ###LEFT-WALL### 2 findings 0 ###LEFT-WALL### 3 suggest 0 ###LEFT-WALL### 6 than 1 the 2 findings 2 findings 3 suggest 3 suggest 4 that 3 suggest 5 more 3 suggest 6 than 6 than 7 half 6 than 17 were 7 half 8 of 7 half 17 were 8 of 13 percent 9 rural 13 percent 10 elderly 13 percent 12 14 13 percent 17 were 18 at 18 at 20 point 19 some 20 point 20 point 21 abused high activeness in health and security dimensions lowers the risk of being abused while those who are low active in community participation have the lowest risk of being abused in both rural and urban areas . 0 ###LEFT-WALL### 2 activeness 0 ###LEFT-WALL### 8 lowers 0 ###LEFT-WALL### 36 . 1 high 2 activeness 2 activeness 3 in 2 activeness 8 lowers 3 in 5 and 4 health 5 and 5 and 7 dimensions 6 security 7 dimensions 8 lowers 10 risk 8 lowers 30 in 9 the 10 risk 10 risk 11 of 11 of 12 being 12 being 13 abused 13 abused 14 while 14 while 15 those 14 while 23 have 15 those 16 who 15 those 17 are 15 those 23 have 16 who 17 are 17 are 18 low 17 are 19 active 19 active 20 in 20 in 22 participation 21 community 22 participation 23 have 26 risk 24 the 25 lowest 24 the 26 risk 26 risk 27 of 27 of 28 being 28 being 29 abused 30 in 33 and 31 both 33 and 32 rural 33 and 33 and 35 areas 34 urban 35 areas being literate ( [elderly] with primary/secondary education ) is revealed to be a significant factor that lowers the risk of abuse in both rural and urban areas . 0 ###LEFT-WALL### 12 be 0 ###LEFT-WALL### 28 . 1 being 2 literate 1 being 9 is 2 literate 5 with 3 ( 5 with 5 with 7 education 5 with 8 ) 6 primary/secondary 7 education 9 is 10 revealed 10 revealed 11 to 11 to 12 be 12 be 15 factor 13 a 15 factor 14 significant 15 factor 15 factor 16 that 15 factor 17 lowers 16 that 17 lowers 17 lowers 19 risk 17 lowers 22 in 18 the 19 risk 19 risk 20 of 20 of 21 abuse 22 in 27 areas 23 both 27 areas 24 rural 25 and 25 and 26 urban 25 and 27 areas these results imply a need for educational programs that bolster positive and proper community interaction , in turn promoting a secure later life for elders , and reducing burden for families and society . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 imply 0 ###LEFT-WALL### 34 . 1 these 2 results 2 results 3 imply 3 imply 32 and 4 a 5 need 5 need 6 for 5 need 27 and 6 for 8 programs 7 educational 8 programs 8 programs 9 that 8 programs 10 bolster 8 programs 19 promoting 9 that 10 bolster 10 bolster 15 interaction 11 positive 12 and 12 and 13 proper 12 and 14 community 14 community 15 interaction 16 , 19 promoting 17 in 18 turn 18 turn 19 promoting 19 promoting 23 life 19 promoting 26 , 20 a 23 life 21 secure 23 life 22 later 23 life 23 life 24 for 24 for 25 elders 26 , 27 and 27 and 29 burden 27 and 30 for 27 and 32 and 28 reducing 29 burden 30 for 31 families 32 and 33 society high activeness in health and security dimensions should also be promoted to keep the elderly healthy and protect from abusive behavior . 0 ###LEFT-WALL### 5 and 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 22 . 1 high 2 activeness 1 high 5 and 2 activeness 3 in 3 in 4 health 5 and 7 dimensions 5 and 17 and 6 security 7 dimensions 8 should 10 be 8 should 17 and 9 also 10 be 10 be 11 promoted 11 promoted 12 to 12 to 13 keep 13 keep 15 elderly 13 keep 16 healthy 14 the 15 elderly 17 and 18 protect 17 and 19 from 19 from 21 behavior 20 abusive 21 behavior none none there is a fairly consistent , [albeit] [non] [-] universal body of research documenting cognitive declines after cancer and its treatments . 0 ###LEFT-WALL### 1 none 0 ###LEFT-WALL### 15 research 0 ###LEFT-WALL### 24 . 1 none 3 there 1 none 14 of 1 none 15 research 2 none 3 there 3 there 4 is 4 is 13 body 5 a 6 fairly 5 a 13 body 6 fairly 7 consistent 7 consistent 8 , 7 consistent 13 body 12 universal 13 body 13 body 14 of 15 research 18 declines 15 research 19 after 16 documenting 18 declines 17 cognitive 18 declines 19 after 21 and 20 cancer 21 and 21 and 23 treatments 22 its 23 treatments while few of these studies have included subjects aged 65 years and older , it is logical to expect that older patients are at risk [of] cognitive decline . here , we use breast cancer as an exemplar disease for inquiry into the intersection of aging and cognitive effects of cancer and its therapies . 0 ###LEFT-WALL### 28 decline 0 ###LEFT-WALL### 29 . 1 while 2 few 1 while 28 decline 2 few 3 of 2 few 5 studies 2 few 6 have 3 of 4 these 5 studies 6 have 6 have 14 , 7 included 8 subjects 7 included 12 and 7 included 14 , 8 subjects 9 aged 10 65 11 years 11 years 12 and 12 and 13 older 14 , 19 expect 15 it 16 is 16 is 17 logical 17 logical 18 to 18 to 19 expect 19 expect 20 that 20 that 22 patients 20 that 23 are 21 older 22 patients 22 patients 23 are 23 are 24 at 23 are 27 cognitive 24 at 25 risk 29 . 32 we 29 . 55 . 30 here 31 , 30 here 32 we 32 we 33 use 33 use 35 cancer 33 use 36 as 33 use 40 for 34 breast 35 cancer 36 as 39 disease 37 an 38 exemplar 37 an 39 disease 38 exemplar 39 disease 40 for 52 and 41 inquiry 42 into 41 inquiry 47 and 42 into 44 intersection 43 the 44 intersection 44 intersection 45 of 45 of 46 aging 47 and 49 effects 47 and 50 of 47 and 52 and 48 cognitive 49 effects 50 of 51 cancer 52 and 54 therapies 53 its 54 therapies there are a striking number of common underlying potential biological risks and pathways for the development of cancer , cancer - related cognitive declines , and aging processes , including the development of a frail phenotype . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 are 0 ###LEFT-WALL### 22 related 0 ###LEFT-WALL### 37 . 1 there 2 are 2 are 5 number 3 a 4 striking 3 a 5 number 4 striking 5 number 5 number 6 of 5 number 17 of 6 of 12 and 7 common 8 underlying 7 common 12 and 8 underlying 11 risks 9 potential 11 risks 10 biological 11 risks 12 and 13 pathways 12 and 14 for 14 for 16 development 15 the 16 development 17 of 18 cancer 18 cancer 20 cancer 19 , 20 cancer 20 cancer 21 - 21 - 22 related 22 related 26 and 23 cognitive 24 declines 24 declines 26 and 25 , 26 and 26 and 28 processes 26 and 29 , 26 and 30 including 26 and 33 of 27 aging 28 processes 30 including 32 development 31 the 32 development 33 of 36 phenotype 34 a 35 frail 34 a 36 phenotype 35 frail 36 phenotype there also are similar structure and functional changes seen in brain imaging studies of cancer patients and those seen with " normal " aging and alzheimer 's disease . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 also 0 ###LEFT-WALL### 29 . 2 also 3 are 2 also 19 seen 3 are 6 and 3 are 10 in 3 are 19 seen 4 similar 5 structure 5 structure 6 and 6 and 8 changes 6 and 9 seen 7 functional 8 changes 10 in 11 brain 11 brain 12 imaging 11 brain 14 of 12 imaging 13 studies 14 of 17 and 15 cancer 16 patients 16 patients 17 and 17 and 18 those 19 seen 20 with 20 with 21 " 20 with 25 and 22 normal 23 " 22 normal 24 aging 22 normal 25 and 25 and 28 disease 26 alzheimer 27 's 27 's 28 disease disentangling the role of these overlapping processes is difficult since they require aged animal models and large samples of older human subjects . 0 ###LEFT-WALL### 1 disentangling 0 ###LEFT-WALL### 8 is 0 ###LEFT-WALL### 23 . 1 disentangling 3 role 1 disentangling 8 is 2 the 3 role 3 role 4 of 4 of 7 processes 5 these 7 processes 6 overlapping 7 processes 8 is 18 samples 9 difficult 10 since 9 difficult 16 and 10 since 11 they 10 since 12 require 11 they 12 require 12 require 15 models 13 aged 14 animal 14 animal 15 models 16 and 17 large 16 and 18 samples 18 samples 19 of 19 of 22 subjects 20 older 22 subjects 21 human 22 subjects from what we do know , frailty and its low cognitive reserve seem to be a clinically useful marker of risk for cognitive decline [after] cancer and its treatments . 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 13 seem 0 ###LEFT-WALL### 30 . 1 from 2 what 1 from 6 , 1 from 8 and 2 what 3 we 2 what 5 know 3 we 4 do 4 do 5 know 7 frailty 8 and 8 and 12 reserve 8 and 13 seem 9 its 12 reserve 10 low 12 reserve 11 cognitive 12 reserve 13 seem 14 to 13 seem 15 be 14 to 15 be 15 be 19 marker 16 a 19 marker 17 clinically 18 useful 18 useful 19 marker 19 marker 20 of 20 of 27 and 21 risk 22 for 21 risk 27 and 22 for 26 cancer 23 cognitive 24 decline 24 decline 26 cancer 27 and 29 treatments 28 its 29 treatments this and other results from this review suggest the value of geriatric assessments to identify older patients at the highest risk [of] cognitive decline . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 8 suggest 0 ###LEFT-WALL### 25 . 1 this 2 and 2 and 4 results 2 and 5 from 2 and 8 suggest 3 other 4 results 5 from 7 review 6 this 7 review 8 suggest 10 value 8 suggest 14 to 9 the 10 value 10 value 11 of 11 of 13 assessments 12 geriatric 13 assessments 14 to 15 identify 15 identify 17 patients 15 identify 18 at 16 older 17 patients 18 at 24 decline 19 the 20 highest 19 the 24 decline 21 risk 24 decline 23 cognitive 24 decline further research is needed to understand the interactions between aging , genetic predisposition , lifestyle factors , and frailty [phenotypes] to best identify the subgroups of older patients at [greatest] risk for decline and to develop behavioral and pharmacological interventions targeting this group . 0 ###LEFT-WALL### 2 research 0 ###LEFT-WALL### 4 needed 0 ###LEFT-WALL### 44 . 1 further 2 research 2 research 3 is 3 is 4 needed 4 needed 5 to 5 to 6 understand 6 understand 18 and 6 understand 34 and 7 the 8 interactions 8 interactions 9 between 8 interactions 11 , 9 between 10 aging 11 , 13 predisposition 11 , 14 , 12 genetic 13 predisposition 14 , 16 factors 14 , 18 and 15 lifestyle 16 factors 17 , 18 and 18 and 19 frailty 18 and 21 to 18 and 32 for 18 and 34 and 21 to 23 identify 22 best 23 identify 23 identify 25 subgroups 23 identify 32 for 24 the 25 subgroups 25 subgroups 26 of 25 subgroups 29 at 26 of 28 patients 27 older 28 patients 29 at 31 risk 33 decline 34 and 34 and 35 to 34 and 36 develop 35 to 36 develop 36 develop 40 interventions 37 behavioral 38 and 38 and 39 pharmacological 38 and 40 interventions 40 interventions 41 targeting 41 targeting 43 group 42 this 43 group we recommend that basic science and population trials be developed specifically for older hosts with intermediate endpoints of relevance to this group , including cognitive function and trajectories of frailty . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 recommend 0 ###LEFT-WALL### 31 . 1 we 2 recommend 2 recommend 19 relevance 2 recommend 20 to 3 that 19 relevance 4 basic 5 science 5 science 6 and 6 and 7 population 6 and 8 trials 6 and 18 of 6 and 19 relevance 8 trials 9 be 9 be 10 developed 10 developed 11 specifically 10 developed 12 for 10 developed 15 with 12 for 14 hosts 13 older 14 hosts 15 with 17 endpoints 16 intermediate 17 endpoints 17 endpoints 18 of 20 to 27 and 21 this 22 group 22 group 23 , 23 , 26 function 23 , 27 and 24 including 26 function 25 cognitive 26 function 27 and 28 trajectories 27 and 29 of 29 of 30 frailty clinicians and their older patients can advance the field by active encouragement [of] and participation in research designed to improve the care and outcomes of the growing population of older cancer patients . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 7 advance 0 ###LEFT-WALL### 33 . 1 clinicians 2 and 2 and 5 patients 2 and 6 can 3 their 5 patients 4 older 5 patients 6 can 7 advance 7 advance 9 field 7 advance 10 by 7 advance 16 in 8 the 9 field 10 by 14 and 11 active 12 encouragement 12 encouragement 14 and 14 and 15 participation 16 in 23 and 17 research 18 designed 17 research 23 and 18 designed 19 to 18 designed 20 improve 19 to 20 improve 20 improve 22 care 21 the 22 care 23 and 24 outcomes 23 and 25 of 25 of 28 population 26 the 28 population 27 growing 28 population 28 population 29 of 29 of 32 patients 30 older 32 patients 31 cancer 32 patients eighteen percent of incident malignancies in the united states are a second ( or subsequent ) cancer . 0 ###LEFT-WALL### 2 percent 0 ###LEFT-WALL### 10 are 0 ###LEFT-WALL### 18 . 1 eighteen 2 percent 2 percent 3 of 2 percent 10 are 3 of 5 malignancies 4 incident 5 malignancies 5 malignancies 6 in 6 in 9 states 7 the 9 states 8 united 9 states 10 are 14 or 11 a 12 second 12 second 14 or 13 ( 14 or 14 or 17 cancer 15 subsequent 16 ) 15 subsequent 17 cancer second primary neoplasms ( spns ) , particularly solid tumors , are a major cause of mortality and serious morbidity among cancer survivors successfully cured of their first cancer . 0 ###LEFT-WALL### 3 neoplasms 0 ###LEFT-WALL### 12 are 0 ###LEFT-WALL### 30 . 1 second 3 neoplasms 2 primary 3 neoplasms 3 neoplasms 5 spns 3 neoplasms 10 tumors 3 neoplasms 12 are 4 ( 5 spns 5 spns 6 ) 7 , 10 tumors 8 particularly 9 solid 9 solid 10 tumors 10 tumors 11 , 12 are 14 major 12 are 15 cause 12 are 21 among 13 a 14 major 15 cause 16 of 16 of 18 and 17 mortality 18 and 18 and 20 morbidity 19 serious 20 morbidity 21 among 23 survivors 22 cancer 23 survivors 23 survivors 25 cured 23 survivors 26 of 24 successfully 25 cured 26 of 29 cancer 27 their 28 first 27 their 29 cancer multiple etiologies may lead to a cancer survivor subsequently being diagnosed with an spn , including radiotherapy for the first cancer , unhealthy lifestyle behaviors , genetic factors , aging , or an interaction between any of these factors . 0 ###LEFT-WALL### 2 etiologies 0 ###LEFT-WALL### 11 diagnosed 1 multiple 2 etiologies 2 etiologies 3 may 3 may 4 lead 4 lead 5 to 5 to 8 survivor 6 a 8 survivor 7 cancer 8 survivor 8 survivor 10 being 9 subsequently 10 being 10 being 11 diagnosed 11 diagnosed 12 with 11 diagnosed 16 including 12 with 14 spn 13 an 14 spn 15 , 16 including 16 including 32 or 16 including 35 between 16 including 40 . 17 radiotherapy 18 for 17 radiotherapy 32 or 18 for 21 cancer 19 the 20 first 19 the 21 cancer 21 cancer 25 behaviors 21 cancer 28 factors 22 , 25 behaviors 23 unhealthy 25 behaviors 24 lifestyle 25 behaviors 25 behaviors 26 , 26 , 28 factors 27 genetic 28 factors 28 factors 30 aging 28 factors 31 , 29 , 30 aging 30 aging 31 , 32 or 34 interaction 33 an 34 interaction 35 between 36 any 36 any 37 of 37 of 39 factors 38 these 39 factors in this article , we discuss these factors and synthesize this information for use in clinical practice , including preventive strategies and screening recommendations for spns . 0 ###LEFT-WALL### 5 we 0 ###LEFT-WALL### 9 and 1 in 3 article 1 in 4 , 1 in 5 we 2 this 3 article 5 we 9 and 6 discuss 8 factors 6 discuss 9 and 7 these 8 factors 9 and 10 synthesize 9 and 13 for 9 and 15 in 9 and 19 including 10 synthesize 12 information 11 this 12 information 13 for 14 use 15 in 17 practice 16 clinical 17 practice 18 , 19 including 19 including 22 and 19 including 27 . 20 preventive 21 strategies 21 strategies 22 and 22 and 24 recommendations 22 and 25 for 23 screening 24 recommendations 25 for 26 spns gait speed is a recommended geriatric assessment of physical performance , but may not be regularly examined in clinical settings . 0 ###LEFT-WALL### 2 speed 0 ###LEFT-WALL### 12 but 0 ###LEFT-WALL### 21 . 1 gait 2 speed 2 speed 12 but 3 is 7 assessment 3 is 12 but 4 a 7 assessment 5 recommended 7 assessment 6 geriatric 7 assessment 7 assessment 8 of 8 of 10 performance 9 physical 10 performance 11 , 12 but 12 but 13 may 13 may 14 not 13 may 15 be 15 be 17 examined 16 regularly 17 examined 17 examined 18 in 18 in 20 settings 19 clinical 20 settings we aimed to investigate whether quadriceps strength tests demonstrate similar predictive ability for [incident] falls as gait speed in older women . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 aimed 0 ###LEFT-WALL### 22 . 1 we 2 aimed 2 aimed 3 to 2 aimed 4 investigate 3 to 4 investigate 4 investigate 5 whether 5 whether 7 strength 5 whether 15 falls 6 quadriceps 7 strength 7 strength 8 tests 7 strength 13 for 7 strength 15 falls 8 tests 9 demonstrate 9 demonstrate 12 ability 9 demonstrate 13 for 10 similar 12 ability 11 predictive 12 ability 15 falls 16 as 15 falls 19 in 16 as 18 speed 17 gait 18 speed 19 in 21 women 20 older 21 women we investigated 135 female volunteers aged mean±sd 76.7±5.0 years ( range 70 - 92 ) at high risk of [fracture] . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 investigated 0 ###LEFT-WALL### 21 . 1 we 2 investigated 2 investigated 3 135 3 135 5 volunteers 3 135 19 of 4 female 5 volunteers 5 volunteers 6 aged 5 volunteers 8 76.7±5.0 6 aged 7 mean±sd 8 76.7±5.0 9 years 8 76.7±5.0 16 at 9 years 11 range 10 ( 11 range 11 range 13 - 11 range 15 ) 12 70 13 - 13 - 14 92 16 at 18 risk 17 high 18 risk 18 risk 19 of participants completed gait speed assessments using the gaitrite electronic walkway system , and quadriceps strength assessments using a hand - held dynamometer ( hhd ) . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 21 held 1 participants 13 and 2 completed 5 assessments 2 completed 6 using 2 completed 13 and 3 gait 5 assessments 4 speed 5 assessments 6 using 11 system 7 the 11 system 8 gaitrite 9 electronic 9 electronic 10 walkway 10 walkway 11 system 12 , 13 and 13 and 14 quadriceps 14 quadriceps 16 assessments 15 strength 16 assessments 16 assessments 17 using 17 using 19 hand 18 a 19 hand 20 - 21 held 21 held 22 dynamometer 21 held 26 . 22 dynamometer 24 hhd 23 ( 24 hhd 24 hhd 25 ) participants reported [incident] falls monthly for 3.7±1.2 years . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 4 falls 0 ###LEFT-WALL### 9 . 1 participants 2 reported 1 participants 4 falls 4 falls 5 monthly 4 falls 6 for 6 for 8 years 7 3.7±1.2 8 years n=99 ( 73 % ) participants fell 355 times during the [follow] [-] up period ( mean fall rate 83 per 100 [person] years ) . 0 ###LEFT-WALL### 6 participants 0 ###LEFT-WALL### 7 fell 0 ###LEFT-WALL### 26 . 1 n=99 4 % 1 n=99 6 participants 2 ( 4 % 3 73 4 % 4 % 5 ) 6 participants 7 fell 7 fell 9 times 7 fell 10 during 8 355 9 times 10 during 15 period 11 the 15 period 14 up 15 period 15 period 19 rate 16 ( 19 rate 17 mean 18 fall 18 fall 19 rate 19 rate 20 83 19 rate 21 per 19 rate 25 ) 21 per 24 years 22 100 24 years we observed a reduced odds ratio for multiple [falls] [(] 0.83 , 95 % ci 0.70 - 0.98 ) and a reduced hazard ratio for time to first fall ( 0.90 , 95 % ci 0.83 - 0.98 ) , according to quadriceps strength . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 observed 0 ###LEFT-WALL### 45 . 1 we 2 observed 2 observed 20 and 2 observed 42 to 3 a 6 ratio 4 reduced 6 ratio 5 odds 6 ratio 6 ratio 7 for 6 ratio 20 and 7 for 8 multiple 8 multiple 11 0.83 8 multiple 15 ci 12 , 15 ci 13 95 15 ci 14 % 15 ci 15 ci 17 - 15 ci 19 ) 16 0.70 17 - 17 - 18 0.98 20 and 24 ratio 20 and 25 for 20 and 27 to 21 a 24 ratio 22 reduced 23 hazard 23 hazard 24 ratio 25 for 26 time 27 to 29 fall 28 first 29 fall 29 fall 31 0.90 29 fall 35 ci 30 ( 31 0.90 31 0.90 32 , 32 , 35 ci 33 95 35 ci 34 % 35 ci 35 ci 36 0.83 35 ci 38 0.98 35 ci 40 , 37 - 38 0.98 38 0.98 39 ) 41 according 42 to 42 to 44 strength 43 quadriceps 44 strength there was also a significantly shorter time to first fall for those with low quadriceps strength ( < 7.0 kg [;] [lowest] tertile ) compared with those with normal quadriceps strength ( estimated means [ 95 % ci ] 1.54 [[] [1.02] [,] [2.06] []] vs [.] 2.23 [[] 1.82 [,] 2.64 []] years [;] p=0.019 [ )( but not for those with low ( < 1.0 m / [s] [ )(vs [.] normal gait speed ( p=0.15 ) . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 was 1 there 2 was 2 was 3 also 2 was 7 time 4 a 7 time 5 significantly 6 shorter 6 shorter 7 time 7 time 8 to 7 time 10 fall 8 to 10 fall 9 first 10 fall 10 fall 11 for 11 for 12 those 12 those 13 with 13 with 15 quadriceps 14 low 15 quadriceps 15 quadriceps 16 strength 15 quadriceps 25 compared 16 strength 23 tertile 16 strength 25 compared 17 ( 23 tertile 18 < 19 7.0 19 7.0 20 kg 20 kg 23 tertile 23 tertile 24 ) 25 compared 26 with 25 compared 28 with 26 with 27 those 28 with 31 strength 28 with 40 1.54 29 normal 31 strength 30 quadriceps 31 strength 31 strength 34 means 32 ( 34 means 33 estimated 34 means 34 means 38 ci 34 means 39 ] 35 [ 38 ci 36 95 38 ci 37 % 38 ci 38 ci 39 ] 40 1.54 46 vs 46 vs 56 p=0.019 48 2.23 54 years 50 1.82 54 years 52 2.64 54 years 54 years 56 p=0.019 56 p=0.019 59 but 56 p=0.019 61 for 56 p=0.019 63 with 59 but 60 not 61 for 62 those 63 with 64 low 64 low 69 / 65 ( 69 / 66 < 67 1.0 67 1.0 68 m 68 m 69 / 69 / 72 )(vs 69 / 78 p=0.15 69 / 80 . 72 )(vs 76 speed 74 normal 76 speed 75 gait 76 speed 77 ( 78 p=0.15 78 p=0.15 79 ) quadriceps strength is a significant predictor of [incident] falls over three years amongst community [-] dwelling older women at high risk [of] fracture . 0 ###LEFT-WALL### 1 quadriceps 0 ###LEFT-WALL### 9 falls 0 ###LEFT-WALL### 24 . 1 quadriceps 2 strength 1 quadriceps 7 of 1 quadriceps 9 falls 2 strength 3 is 3 is 6 predictor 4 a 5 significant 4 a 6 predictor 5 significant 6 predictor 6 predictor 7 of 9 falls 10 over 10 over 11 three 11 three 12 years 11 three 23 fracture 12 years 13 amongst 12 years 23 fracture 13 amongst 18 women 14 community 16 dwelling 16 dwelling 18 women 17 older 18 women 18 women 19 at 19 at 21 risk 20 high 21 risk quadriceps strength tests may be an acceptable alternative to gait speed for geriatric assessments of [falls] risk . 0 ###LEFT-WALL### 3 tests 0 ###LEFT-WALL### 5 be 0 ###LEFT-WALL### 18 . 1 quadriceps 3 tests 2 strength 3 tests 3 tests 4 may 4 may 5 be 5 be 8 alternative 6 an 7 acceptable 6 an 8 alternative 7 acceptable 8 alternative 8 alternative 9 to 9 to 11 speed 10 gait 11 speed 11 speed 12 for 12 for 14 assessments 13 geriatric 14 assessments 14 assessments 15 of 15 of 17 risk none none objective : to summarize the experience and characteristics of the modified laparoscopic splenectomy [for] massive splenomegaly in the treatment of children with hematologic disease . 0 ###LEFT-WALL### 1 none 0 ###LEFT-WALL### 6 summarize 0 ###LEFT-WALL### 27 . 1 none 3 objective 1 none 5 to 1 none 6 summarize 2 none 3 objective 3 objective 4 : 4 : 5 to 6 summarize 9 and 7 the 8 experience 8 experience 9 and 9 and 10 characteristics 9 and 11 of 9 and 17 massive 11 of 15 splenectomy 12 the 15 splenectomy 13 modified 15 splenectomy 14 laparoscopic 15 splenectomy 17 massive 18 splenomegaly 17 massive 19 in 17 massive 24 with 19 in 21 treatment 20 the 21 treatment 21 treatment 22 of 22 of 23 children 24 with 26 disease 25 hematologic 26 disease methods : the clinical data of 30 cases [of] laparoscopic splenectomy for [massive] splenomegaly of children with hematologic disease from march 2007 to december 2011 was analyzed retrospectively . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 27 analyzed 0 ###LEFT-WALL### 29 . 2 : 5 data 2 : 8 cases 3 the 5 data 4 clinical 5 data 5 data 6 of 5 data 8 cases 6 of 7 30 8 cases 11 splenectomy 8 cases 12 for 10 laparoscopic 11 splenectomy 12 for 25 2011 14 splenomegaly 25 2011 15 of 16 children 15 of 25 2011 16 children 17 with 17 with 19 disease 18 hematologic 19 disease 19 disease 20 from 19 disease 23 to 20 from 21 march 21 march 22 2007 23 to 24 december 25 2011 26 was 26 was 27 analyzed 27 analyzed 28 retrospectively there were 18 male and 12 female patients , aging from 2 to 14 years . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 were 1 there 2 were 2 were 5 and 3 18 5 and 4 male 5 and 5 and 8 patients 5 and 10 aging 6 12 8 patients 7 female 8 patients 9 , 10 aging 10 aging 15 years 10 aging 16 . 11 from 13 to 12 2 13 to 13 to 14 14 13 to 15 years primary disease included mediterranean anemia ( 17 cases ) , hereditary spherocytosis ( 4 cases [ )(and idiopathic thrombocytopenic purpura ( itp , 9 cases ) . 0 ###LEFT-WALL### 2 disease 0 ###LEFT-WALL### 3 included 0 ###LEFT-WALL### 27 . 1 primary 2 disease 2 disease 3 included 3 included 5 anemia 4 mediterranean 5 anemia 5 anemia 8 cases 5 anemia 12 spherocytosis 6 ( 8 cases 7 17 8 cases 8 cases 9 ) 10 , 12 spherocytosis 11 hereditary 12 spherocytosis 12 spherocytosis 17 )(and 12 spherocytosis 26 ) 13 ( 17 )(and 14 4 15 cases 15 cases 17 )(and 17 )(and 20 purpura 17 )(and 22 itp 17 )(and 26 ) 18 idiopathic 20 purpura 19 thrombocytopenic 20 purpura 21 ( 22 itp 22 itp 25 cases 22 itp 26 ) 23 , 25 cases 24 9 25 cases 25 cases 26 ) dissection started with cutting off the gastrosplenic ligaments and lesser sac to fully reveal the splenic hilum , the splenic artery was clamped twice with 10 mm tiatanum [clamp] . 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 18 , 0 ###LEFT-WALL### 30 . 1 dissection 2 started 1 dissection 9 and 2 started 3 with 3 with 4 cutting 4 cutting 5 off 4 cutting 8 ligaments 6 the 8 ligaments 7 gastrosplenic 8 ligaments 9 and 11 sac 9 and 12 to 9 and 14 reveal 10 lesser 11 sac 12 to 14 reveal 13 fully 14 reveal 14 reveal 17 hilum 15 the 17 hilum 16 splenic 17 hilum 18 , 21 artery 18 , 23 clamped 19 the 21 artery 20 splenic 21 artery 21 artery 22 was 22 was 23 clamped 23 clamped 24 twice 23 clamped 25 with 25 with 28 tiatanum 26 10 27 mm 27 mm 28 tiatanum when most of blood stored in the spleen back to heart through the veins and the splenic volume had already decreased , the splenic vein was ligated with 10 mm titanium [clip] and cut with ligsure and splenic pedicle separated . 0 ###LEFT-WALL### 25 vein 0 ###LEFT-WALL### 33 and 0 ###LEFT-WALL### 41 . 1 when 2 most 1 when 21 decreased 1 when 22 , 1 when 25 vein 2 most 3 of 2 most 5 stored 2 most 6 in 2 most 9 back 3 of 4 blood 6 in 8 spleen 7 the 8 spleen 9 back 10 to 10 to 11 heart 11 heart 18 volume 11 heart 19 had 12 through 18 volume 13 the 14 veins 14 veins 15 and 15 and 17 splenic 15 and 18 volume 16 the 17 splenic 18 volume 19 had 19 had 20 already 19 had 21 decreased 23 the 25 vein 24 splenic 25 vein 25 vein 33 and 26 was 27 ligated 26 was 33 and 27 ligated 28 with 28 with 31 titanium 29 10 30 mm 30 mm 31 titanium 33 and 34 cut 34 cut 35 with 34 cut 39 pedicle 35 with 37 and 36 ligsure 37 and 37 and 38 splenic 39 pedicle 40 separated the surgery and complication were recorded . 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 6 recorded 0 ###LEFT-WALL### 7 . 1 the 2 surgery 2 surgery 3 and 3 and 4 complication 3 and 5 were 5 were 6 recorded for 1 week after surgery , the hemoglobin and platelet counts were reviewed . 0 ###LEFT-WALL### 1 for 0 ###LEFT-WALL### 12 were 0 ###LEFT-WALL### 14 . 1 for 3 week 1 for 12 were 2 1 3 week 3 week 4 after 4 after 9 and 5 surgery 6 , 6 , 8 hemoglobin 6 , 9 and 7 the 8 hemoglobin 9 and 10 platelet 11 counts 12 were 12 were 13 reviewed results : twenty - six cases were performed successfully , and 4 cases were converted to open procedure . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 6 cases 2 : 11 and 2 : 19 . 3 twenty 4 - 4 - 5 six 4 - 6 cases 6 cases 7 were 7 were 11 and 8 performed 9 successfully 8 performed 11 and 10 , 11 and 11 and 17 open 12 4 13 cases 13 cases 14 were 14 were 15 converted 15 converted 16 to 16 to 17 open 17 open 18 procedure of the 4 cases , [2] cases [was] obesity because of idiopathic thrombocytopenic purpura , 1 case was β thalassaemia combined severe liver enlargement , and 1 case was after partial splenic embolization . 0 ###LEFT-WALL### 5 , 0 ###LEFT-WALL### 15 , 0 ###LEFT-WALL### 34 . 1 of 3 4 1 of 5 , 2 the 3 4 4 cases 5 , 5 , 7 cases 7 cases 9 obesity 7 cases 11 of 10 because 11 of 11 of 14 purpura 12 idiopathic 14 purpura 13 thrombocytopenic 14 purpura 15 , 17 case 15 , 18 was 15 , 26 and 16 1 17 case 17 case 18 was 18 was 24 enlargement 19 β 21 combined 20 thalassaemia 21 combined 21 combined 23 liver 22 severe 23 liver 23 liver 24 enlargement 25 , 26 and 26 and 28 case 26 and 29 was 27 1 28 case 28 case 29 was 29 was 30 after 30 after 33 embolization 31 partial 33 embolization 32 splenic 33 embolization in cases of laparoscopic splenectomy , operation time was 110 to 130 minutes , with an average of 120 minutes , and blood loss during operation was 35 to 180 ml , with an average of 45 ml . 0 ###LEFT-WALL### 8 time 0 ###LEFT-WALL### 9 was 0 ###LEFT-WALL### 39 . 1 in 2 cases 1 in 8 time 2 cases 3 of 3 of 7 operation 4 laparoscopic 7 operation 5 splenectomy 6 , 5 splenectomy 7 operation 8 time 9 was 9 was 22 and 10 110 11 to 11 to 12 130 11 to 22 and 13 minutes 15 with 13 minutes 22 and 14 , 15 with 15 with 17 average 15 with 21 , 16 an 17 average 17 average 18 of 18 of 20 minutes 19 120 20 minutes 21 , 22 and 22 and 24 loss 22 and 32 , 22 and 33 with 22 and 36 of 23 blood 24 loss 24 loss 25 during 25 during 31 ml 26 operation 27 was 27 was 29 to 28 35 29 to 29 to 30 180 30 180 31 ml 33 with 35 average 34 an 35 average 36 of 38 ml 37 45 38 ml compared with pre - operation , the hemoglobin of mediterranean anemia and hereditary spherocytosis patients were [(] 92 ± [8] ) g/l , and blood platelet count of itp patients was [(] 127 ± 20 )×10 ( 9 )/l , and they increased [obviously] at 1 week after operation ( [t] = 4.175 and 8.253 , [both] p = 0.000 ) . 1 compared 2 with 1 compared 4 - 1 compared 12 and 2 with 3 pre 5 operation 6 , 6 , 8 hemoglobin 6 , 12 and 7 the 8 hemoglobin 8 hemoglobin 9 of 9 of 11 anemia 10 mediterranean 11 anemia 12 and 15 patients 12 and 24 and 13 hereditary 14 spherocytosis 14 spherocytosis 15 patients 16 were 22 g/l 16 were 24 and 18 92 22 g/l 19 ± 21 ) 19 ± 22 g/l 23 , 24 and 24 and 25 blood 24 and 33 127 25 blood 26 platelet 26 platelet 27 count 26 platelet 31 was 27 count 28 of 27 count 31 was 28 of 30 patients 29 itp 30 patients 33 127 41 and 33 127 43 increased 34 ± 41 and 35 20 36 )×10 36 )×10 39 )/l 37 ( 39 )/l 38 9 39 )/l 39 )/l 40 , 40 , 41 and 41 and 42 they 41 and 43 increased 43 increased 45 at 43 increased 48 after 45 at 47 week 46 1 47 week 48 after 49 operation 49 operation 54 and 50 ( 54 and 52 = 53 4.175 53 4.175 54 and 54 and 55 8.253 54 and 59 = 54 and 62 . 56 , 59 = 58 p 59 = 59 = 60 0.000 59 = 61 ) conclusion : the modified surgical method [make] the laparoscopic splenectomy [for] massive splenomegaly in many children with hematologic diseases possible [,] which was thought to be impossible in the past . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 24 thought 1 conclusion 2 : 2 : 6 method 3 the 6 method 4 modified 6 method 5 surgical 6 method 8 the 10 splenectomy 9 laparoscopic 10 splenectomy 10 splenectomy 12 massive 10 splenectomy 22 which 10 splenectomy 23 was 10 splenectomy 24 thought 12 massive 13 splenomegaly 12 massive 14 in 12 massive 17 with 14 in 16 children 15 many 16 children 17 with 19 diseases 17 with 20 possible 18 hematologic 19 diseases 22 which 23 was 24 thought 25 to 24 thought 31 . 25 to 26 be 26 be 27 impossible 27 impossible 28 in 28 in 30 past 29 the 30 past a novel point mutation resulting in a glutamate - to [-] glycine substitution in prnp at codon 200 , e200g with codon 129 mv polymorphism [(] cis valine ) and type 2 prpsc was identified in a patient with a prolonged disease course leading to pathology - proven jakob - creutzfeldt disease . 0 ###LEFT-WALL### 30 and 0 ###LEFT-WALL### 47 - 0 ###LEFT-WALL### 53 . 1 a 2 novel 1 a 4 mutation 2 novel 3 point 3 point 4 mutation 4 mutation 5 resulting 4 mutation 6 in 4 mutation 30 and 6 in 8 glutamate 7 a 8 glutamate 8 glutamate 10 to 8 glutamate 20 e200g 9 - 10 to 10 to 13 substitution 10 to 19 , 12 glycine 13 substitution 13 substitution 14 in 14 in 15 prnp 15 prnp 16 at 16 at 17 codon 17 codon 18 200 19 , 20 e200g 20 e200g 21 with 20 e200g 29 ) 21 with 28 valine 22 codon 28 valine 23 129 28 valine 24 mv 25 polymorphism 25 polymorphism 28 valine 27 cis 28 valine 30 and 31 type 30 and 33 prpsc 30 and 44 leading 32 2 33 prpsc 33 prpsc 34 was 34 was 35 identified 35 identified 36 in 36 in 38 patient 37 a 38 patient 38 patient 39 with 39 with 43 course 40 a 43 course 41 prolonged 42 disease 42 disease 43 course 43 course 44 leading 44 leading 45 to 45 to 46 pathology 47 - 49 jakob 47 - 50 - 48 proven 49 jakob 50 - 52 disease 51 creutzfeldt 52 disease despite the same codon as the most common genetic form of human prnp mutation , e200k , this novel mutation ( e200g ) presented with a different clinical and pathological phenotype , including prolonged duration , large vacuoles , no vacuolation in the hippocampus , severe neuronal loss in the thalamus , mild cerebellar involvement , and abundant punctate linear and curvilinear deposition of prpsc in synaptic boutons and axonal terminals along the dendrites . 0 ###LEFT-WALL### 20 mutation 0 ###LEFT-WALL### 24 presented 0 ###LEFT-WALL### 75 . 1 despite 4 codon 1 despite 20 mutation 2 the 3 same 3 same 4 codon 4 codon 5 as 4 codon 11 of 5 as 10 form 6 the 10 form 7 most 8 common 8 common 10 form 9 genetic 10 form 11 of 14 mutation 12 human 14 mutation 13 prnp 14 mutation 14 mutation 16 e200k 15 , 16 e200k 16 e200k 17 , 18 this 20 mutation 19 novel 20 mutation 20 mutation 22 e200g 20 mutation 24 presented 21 ( 22 e200g 22 e200g 23 ) 24 presented 25 with 24 presented 33 including 24 presented 57 and 25 with 31 phenotype 26 a 31 phenotype 27 different 31 phenotype 28 clinical 29 and 29 and 30 pathological 29 and 31 phenotype 32 , 33 including 33 including 35 duration 33 including 45 , 34 prolonged 35 duration 35 duration 38 vacuoles 36 , 38 vacuoles 37 large 38 vacuoles 38 vacuoles 41 vacuolation 38 vacuoles 45 , 39 , 41 vacuolation 40 no 41 vacuolation 41 vacuolation 42 in 41 vacuolation 45 , 42 in 44 hippocampus 43 the 44 hippocampus 46 severe 48 loss 47 neuronal 48 loss 48 loss 49 in 48 loss 52 , 49 in 51 thalamus 50 the 51 thalamus 52 , 55 involvement 52 , 57 and 53 mild 55 involvement 54 cerebellar 55 involvement 56 , 57 and 57 and 63 deposition 57 and 66 in 58 abundant 59 punctate 59 punctate 63 deposition 60 linear 61 and 61 and 62 curvilinear 61 and 63 deposition 63 deposition 64 of 64 of 65 prpsc 66 in 69 and 67 synaptic 68 boutons 68 boutons 69 and 69 and 71 terminals 69 and 72 along 70 axonal 71 terminals 72 along 74 dendrites 73 the 74 dendrites energy intake under [-] reporting ( ur ) is a concern in nutritional epidemiological studies , as it may distort the relationships between dietary habits and health . 0 ###LEFT-WALL### 2 intake 0 ###LEFT-WALL### 9 is 0 ###LEFT-WALL### 16 , 0 ###LEFT-WALL### 28 . 1 energy 2 intake 2 intake 3 under 2 intake 9 is 3 under 5 reporting 5 reporting 7 ur 6 ( 7 ur 7 ur 8 ) 9 is 11 concern 10 a 11 concern 11 concern 12 in 12 in 15 studies 13 nutritional 15 studies 14 epidemiological 15 studies 16 , 20 distort 17 as 18 it 17 as 19 may 17 as 20 distort 18 it 19 may 20 distort 22 relationships 20 distort 23 between 21 the 22 relationships 23 between 26 and 24 dietary 25 habits 25 habits 26 and 26 and 27 health although ur is known to be associated with certain characteristics , few studies have investigated them in france . 0 ###LEFT-WALL### 13 studies 0 ###LEFT-WALL### 15 investigated 0 ###LEFT-WALL### 19 . 1 although 2 ur 1 although 4 known 1 although 11 , 1 although 13 studies 2 ur 3 is 3 is 4 known 4 known 5 to 4 known 7 associated 5 to 6 be 6 be 7 associated 7 associated 8 with 8 with 10 characteristics 9 certain 10 characteristics 12 few 13 studies 13 studies 14 have 14 have 15 investigated 15 investigated 16 them 15 investigated 17 in 17 in 18 france therefore , the goal of the present study was to assess the prevalence and characteristics of ur in french adults . 0 ###LEFT-WALL### 4 goal 0 ###LEFT-WALL### 21 . 1 therefore 2 , 1 therefore 4 goal 3 the 4 goal 4 goal 5 of 4 goal 9 was 5 of 8 study 6 the 8 study 7 present 8 study 9 was 10 to 9 was 11 assess 10 to 11 assess 11 assess 14 and 11 assess 18 in 12 the 14 and 13 prevalence 14 and 14 and 15 characteristics 14 and 16 of 16 of 17 ur 18 in 20 adults 19 french 20 adults ur was defined according to goldberg 's classification . 0 ###LEFT-WALL### 1 ur 0 ###LEFT-WALL### 3 defined 0 ###LEFT-WALL### 9 . 1 ur 2 was 2 was 3 defined 3 defined 5 to 4 according 5 to 5 to 8 classification 6 goldberg 7 's 7 's 8 classification a sample of 1567 adults was drawn from the nationally representative french dietary survey ( individuelle nationale des consommations alimentaires [2] 2006 - 7 ) . 0 ###LEFT-WALL### 2 sample 0 ###LEFT-WALL### 7 drawn 0 ###LEFT-WALL### 26 . 1 a 2 sample 2 sample 3 of 2 sample 6 was 3 of 5 adults 4 1567 5 adults 6 was 7 drawn 7 drawn 8 from 8 from 14 survey 9 the 14 survey 10 nationally 11 representative 11 representative 14 survey 12 french 14 survey 13 dietary 14 survey 14 survey 20 alimentaires 15 ( 20 alimentaires 16 individuelle 17 nationale 17 nationale 18 des 18 des 19 consommations 19 consommations 20 alimentaires 20 alimentaires 23 - 20 alimentaires 25 ) 22 2006 23 - 23 - 24 7 food [intake] ( 7 d record ) , dietary habits , socio - economic status , [region] of residence , sedentary behaviour and weight perception variables were assessed . 0 ###LEFT-WALL### 23 and 0 ###LEFT-WALL### 28 assessed 0 ###LEFT-WALL### 29 . 1 food 6 record 1 food 8 , 3 ( 6 record 4 7 5 d 5 d 6 record 6 record 7 ) 8 , 10 habits 8 , 11 , 9 dietary 10 habits 11 , 22 behaviour 11 , 23 and 12 socio 15 status 12 socio 22 behaviour 13 - 15 status 14 economic 15 status 15 status 18 of 15 status 20 , 16 , 18 of 18 of 19 residence 18 of 20 , 21 sedentary 22 behaviour 23 and 26 variables 23 and 27 were 24 weight 26 variables 25 perception 26 variables 27 were 28 assessed multivariate logistic regression was used to investigate the associations between ur and a number of covariates . 0 ###LEFT-WALL### 3 regression 0 ###LEFT-WALL### 7 investigate 0 ###LEFT-WALL### 17 . 1 multivariate 2 logistic 2 logistic 3 regression 3 regression 4 was 4 was 5 used 5 used 6 to 6 to 7 investigate 7 investigate 9 associations 7 investigate 10 between 8 the 9 associations 10 between 12 and 11 ur 12 and 12 and 14 number 12 and 15 of 13 a 14 number 15 of 16 covariates the overall prevalence of ur was 22.5 % , similar in men and women . 0 ###LEFT-WALL### 3 prevalence 0 ###LEFT-WALL### 6 was 1 the 3 prevalence 2 overall 3 prevalence 3 prevalence 4 of 3 prevalence 6 was 4 of 5 ur 6 was 8 % 7 22.5 8 % 8 % 10 similar 9 , 10 similar 10 similar 11 in 10 similar 15 . 11 in 13 and 12 men 13 and 13 and 14 women in both sexes , ur was positively associated with overweight and protein intake and inversely associated with age . 0 ###LEFT-WALL### 5 ur 0 ###LEFT-WALL### 6 was 0 ###LEFT-WALL### 19 . 1 in 3 sexes 1 in 4 , 1 in 5 ur 2 both 3 sexes 5 ur 6 was 6 was 14 and 7 positively 8 associated 8 associated 9 with 8 associated 14 and 9 with 11 and 10 overweight 11 and 11 and 13 intake 12 protein 13 intake 14 and 16 associated 14 and 17 with 15 inversely 16 associated 17 with 18 age in women , ur was associated with eating lunch in the office , poor perception of diet quality and sedentary behaviour and was inversely associated with educational level , residence in the paris region , cereal product intake and eating lunch in a friend 's or family member 's home . 0 ###LEFT-WALL### 4 ur 0 ###LEFT-WALL### 22 and 0 ###LEFT-WALL### 39 and 0 ###LEFT-WALL### 49 's 0 ###LEFT-WALL### 51 . 1 in 2 women 1 in 3 , 1 in 4 ur 4 ur 22 and 5 was 6 associated 5 was 22 and 6 associated 7 with 7 with 8 eating 8 eating 9 lunch 9 lunch 10 in 10 in 19 and 11 the 12 office 12 office 13 , 13 , 15 perception 13 , 19 and 14 poor 15 perception 15 perception 16 of 16 of 18 quality 17 diet 18 quality 19 and 21 behaviour 20 sedentary 21 behaviour 22 and 23 was 22 and 38 intake 23 was 25 associated 24 inversely 25 associated 25 associated 26 with 26 with 36 cereal 27 educational 36 cereal 28 level 30 residence 28 level 35 , 28 level 36 cereal 29 , 30 residence 30 residence 31 in 30 residence 35 , 31 in 34 region 32 the 34 region 33 paris 34 region 37 product 38 intake 39 and 40 eating 39 and 49 's 40 eating 46 or 40 eating 49 's 41 lunch 42 in 41 lunch 46 or 42 in 45 's 43 a 44 friend 44 friend 45 's 46 or 48 member 47 family 48 member 49 's 50 home in men , ur was positively associated with a history of slimming and inversely associated with dairy product intake and eating lunch at a staff canteen . 0 ###LEFT-WALL### 4 ur 0 ###LEFT-WALL### 5 was 0 ###LEFT-WALL### 27 . 1 in 2 men 1 in 3 , 1 in 4 ur 4 ur 5 was 5 was 13 and 6 positively 7 associated 7 associated 8 with 7 associated 13 and 8 with 10 history 9 a 10 history 10 history 11 of 11 of 12 slimming 13 and 20 and 13 and 22 lunch 13 and 23 at 14 inversely 15 associated 15 associated 16 with 15 associated 20 and 16 with 19 intake 17 dairy 18 product 18 product 19 intake 20 and 21 eating 23 at 26 canteen 24 a 25 staff 24 a 26 canteen 25 staff 26 canteen in conclusion , ur is prevalent in french adults and is associated with several different characteristics . 0 ###LEFT-WALL### 2 conclusion 0 ###LEFT-WALL### 3 , 0 ###LEFT-WALL### 17 . 1 in 2 conclusion 3 , 4 ur 3 , 10 and 4 ur 10 and 5 is 6 prevalent 5 is 10 and 6 prevalent 7 in 7 in 9 adults 8 french 9 adults 10 and 11 is 11 is 12 associated 12 associated 13 with 13 with 16 characteristics 14 several 16 characteristics 15 different 16 characteristics it is important to take account [of] ur when investigating diet [-] disease associations in adults . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 17 . 1 it 2 is 2 is 3 important 3 important 4 to 3 important 5 take 4 to 5 take 5 take 8 ur 5 take 9 when 6 account 8 ur 9 when 10 investigating 10 investigating 14 associations 10 investigating 15 in 11 diet 14 associations 13 disease 14 associations 15 in 16 adults background : the serum level of amylase [(] [sam] [ )(is commonly used as a biochemical marker for diagnosis and management of pancreatic disorders . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 25 . 2 : 5 level 2 : 13 used 3 the 5 level 4 serum 5 level 5 level 6 of 5 level 11 )(is 6 of 7 amylase 11 )(is 13 used 12 commonly 13 used 13 used 14 as 14 as 17 marker 15 a 16 biochemical 15 a 17 marker 16 biochemical 17 marker 17 marker 18 for 18 for 20 and 19 diagnosis 20 and 20 and 21 management 20 and 22 of 22 of 24 disorders 23 pancreatic 24 disorders however , the use of the urine level of amylase ( uam ) is limited in practice , because the diagnostic ability of uam is inferior to that [of] [sam] . 0 ###LEFT-WALL### 4 use 0 ###LEFT-WALL### 14 is 1 however 2 , 1 however 4 use 3 the 4 use 4 use 5 of 4 use 14 is 5 of 8 level 6 the 8 level 7 urine 8 level 8 level 9 of 9 of 10 amylase 10 amylase 12 uam 11 ( 12 uam 12 uam 13 ) 14 is 15 limited 15 limited 16 in 15 limited 19 because 16 in 17 practice 18 , 19 because 19 because 22 ability 19 because 25 is 19 because 31 . 20 the 22 ability 21 diagnostic 22 ability 22 ability 23 of 22 ability 25 is 23 of 24 uam 25 is 26 inferior 26 inferior 27 to 27 to 28 that in the present study , the possible concordance of uam - rerated parameters [with] [sam] was investigated , and evaluate the usefulness of uam for management of hyperamylasemia . 0 ###LEFT-WALL### 8 concordance 0 ###LEFT-WALL### 19 and 0 ###LEFT-WALL### 29 . 1 in 4 study 1 in 5 , 1 in 8 concordance 2 the 4 study 3 present 4 study 6 the 8 concordance 7 possible 8 concordance 8 concordance 9 of 8 concordance 16 was 9 of 13 parameters 10 uam 11 - 10 uam 13 parameters 12 rerated 13 parameters 16 was 19 and 17 investigated 19 and 18 , 19 and 19 and 20 evaluate 20 evaluate 22 usefulness 21 the 22 usefulness 22 usefulness 23 of 23 of 24 uam 24 uam 25 for 25 for 26 management 26 management 27 of 27 of 28 hyperamylasemia methods : from june 1995 to october 2009 , 804 samples of both urine and blood were collected from 128 patients in order to measure the serum level of amylase ( [sam] [ )(and the urine level of amylase ( uam ) [and] creatinine ( ucr ) . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 9 , 1 methods 2 : 2 : 3 from 2 : 6 to 3 from 4 june 4 june 5 1995 6 to 7 october 7 october 8 2009 9 , 11 samples 9 , 18 collected 10 804 11 samples 11 samples 12 of 11 samples 17 were 12 of 15 and 13 both 15 and 14 urine 15 and 15 and 16 blood 17 were 18 collected 18 collected 19 from 18 collected 24 to 19 from 21 patients 20 128 21 patients 21 patients 22 in 22 in 23 order 24 to 25 measure 25 measure 34 )(and 26 the 28 level 27 serum 28 level 28 level 29 of 28 level 34 )(and 29 of 30 amylase 31 ( 34 )(and 34 )(and 37 level 35 the 37 level 36 urine 37 level 37 level 38 of 38 of 39 amylase 39 amylase 44 creatinine 40 ( 44 creatinine 41 uam 42 ) 41 uam 44 creatinine 44 creatinine 46 ucr 44 creatinine 48 . 45 ( 46 ucr 46 ucr 47 ) concordance of parameters using uam compared to [sam] was assessed . 0 ###LEFT-WALL### 1 concordance 0 ###LEFT-WALL### 10 assessed 0 ###LEFT-WALL### 11 . 1 concordance 2 of 1 concordance 9 was 2 of 3 parameters 3 parameters 4 using 3 parameters 7 to 4 using 5 uam 4 using 6 compared 6 compared 7 to 9 was 10 assessed parameters used were uam , amylase creatinine clearance [ratio] ( accr [ )(, and the ratio of uam to ucr ( uam/ucr ) . 0 ###LEFT-WALL### 1 parameters 0 ###LEFT-WALL### 3 were 1 parameters 2 used 1 parameters 3 were 3 were 8 clearance 4 uam 5 , 4 uam 8 clearance 6 amylase 8 clearance 7 creatinine 8 clearance 8 clearance 14 and 10 ( 14 and 11 accr 14 and 13 )(, 14 and 14 and 16 ratio 14 and 17 of 14 and 19 to 14 and 24 . 15 the 16 ratio 17 of 18 uam 19 to 20 ucr 20 ucr 22 uam/ucr 21 ( 22 uam/ucr 22 uam/ucr 23 ) results [:] uam/ucr had the best correlation with [sam] ( r = 0.779 , p < 0.001 ) compared to uam ( r = 0.620 , p < 0.001 ) and to accr ( r = 0.374 , p < 0.001 ) , when [sam] was [over] the standard level . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 19 compared 0 ###LEFT-WALL### 43 , 0 ###LEFT-WALL### 46 was 0 ###LEFT-WALL### 51 . 1 results 3 uam/ucr 1 results 8 with 1 results 12 = 1 results 19 compared 3 uam/ucr 4 had 4 had 7 correlation 4 had 8 with 5 the 6 best 5 the 7 correlation 10 ( 12 = 11 r 12 = 12 = 13 0.779 13 0.779 16 < 14 , 16 < 15 p 16 < 16 < 17 0.001 16 < 18 ) 19 compared 31 and 20 to 21 uam 20 to 31 and 21 uam 24 = 21 uam 28 < 22 ( 24 = 23 r 24 = 24 = 25 0.620 24 = 26 , 27 p 28 < 28 < 29 0.001 28 < 30 ) 31 and 32 to 32 to 33 accr 33 accr 36 = 33 accr 40 < 34 ( 36 = 35 r 36 = 36 = 37 0.374 36 = 38 , 38 , 40 < 39 p 40 < 40 < 41 0.001 40 < 42 ) 43 , 44 when 44 when 46 was 46 was 49 standard 46 was 50 level 48 the 49 standard the area under the receiver operating characteristic curve of uam/ucr ( 0.884 ) was significantly higher than that of uam ( 0.766 ) and [of] accr ( 0.666 ) ( [p] < 0.001 for each ) . 0 ###LEFT-WALL### 2 area 0 ###LEFT-WALL### 14 was 0 ###LEFT-WALL### 37 . 1 the 2 area 2 area 3 under 2 area 12 0.884 2 area 14 was 3 under 8 curve 4 the 8 curve 5 receiver 6 operating 6 operating 8 curve 7 characteristic 8 curve 8 curve 9 of 9 of 10 uam/ucr 11 ( 12 0.884 12 0.884 13 ) 14 was 16 higher 15 significantly 16 higher 16 higher 17 than 17 than 24 and 18 that 19 of 18 that 24 and 19 of 20 uam 20 uam 22 0.766 21 ( 22 0.766 22 0.766 23 ) 24 and 26 accr 24 and 33 0.001 26 accr 28 0.666 27 ( 28 0.666 28 0.666 29 ) 30 ( 33 0.001 32 < 33 0.001 33 0.001 34 for 33 0.001 36 ) 34 for 35 each the cutoff value of uam/ucr was 569.8 , with a sensitivity of 81.0 % and a specificity of 83.1 % . 0 ###LEFT-WALL### 3 value 0 ###LEFT-WALL### 6 was 1 the 3 value 2 cutoff 3 value 3 value 4 of 3 value 6 was 4 of 5 uam/ucr 6 was 7 569.8 7 569.8 9 with 8 , 9 with 9 with 15 and 9 with 21 . 10 a 11 sensitivity 11 sensitivity 12 of 11 sensitivity 15 and 12 of 14 % 13 81.0 14 % 15 and 17 specificity 15 and 18 of 16 a 17 specificity 18 of 20 % 19 83.1 20 % conclusions : the uam/ucr ratio correlated [with] [sam] , and may be an alternative [to] s [sam] for prediction of hyperamylasemia . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 12 be 0 ###LEFT-WALL### 22 . 2 : 5 ratio 2 : 10 and 3 the 5 ratio 4 uam/ucr 5 ratio 5 ratio 10 and 6 correlated 10 and 9 , 10 and 10 and 11 may 11 may 12 be 12 be 16 s 13 an 16 s 14 alternative 16 s 16 s 18 for 18 for 19 prediction 19 prediction 20 of 20 of 21 hyperamylasemia use of urine samples results in a decreased need for blood sampling , which is especially beneficial in pediatric patients . 0 ###LEFT-WALL### 1 use 0 ###LEFT-WALL### 4 samples 0 ###LEFT-WALL### 13 , 0 ###LEFT-WALL### 21 . 1 use 2 of 1 use 4 samples 2 of 3 urine 4 samples 5 results 4 samples 6 in 6 in 9 need 7 a 9 need 8 decreased 9 need 9 need 10 for 10 for 12 sampling 11 blood 12 sampling 13 , 14 which 13 , 15 is 14 which 15 is 15 is 16 especially 15 is 17 beneficial 17 beneficial 18 in 18 in 20 patients 19 pediatric 20 patients there is a well - documented shortage of physician researchers , and numerous training programs have been launched to facilitate development of new physician scientists . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 26 . 1 there 2 is 2 is 4 well 3 a 4 well 4 well 7 shortage 5 - 7 shortage 6 documented 7 shortage 7 shortage 8 of 7 shortage 11 , 8 of 10 researchers 9 physician 10 researchers 12 and 15 programs 12 and 18 launched 13 numerous 14 training 14 training 15 programs 15 programs 16 have 16 have 17 been 17 been 18 launched 18 launched 19 to 19 to 20 facilitate 20 facilitate 21 development 21 development 22 of 22 of 25 scientists 23 new 24 physician 24 physician 25 scientists short - term research training programs are the most practical form of research exposure for most medical students , and the summer between their first and second years of medical school is generally the longest period they can devote solely to research . 0 ###LEFT-WALL### 1 short 0 ###LEFT-WALL### 2 - 0 ###LEFT-WALL### 39 devote 0 ###LEFT-WALL### 43 . 2 - 6 programs 2 - 32 is 3 term 6 programs 4 research 6 programs 5 training 6 programs 6 programs 7 are 8 the 11 form 9 most 10 practical 10 practical 11 form 11 form 12 of 11 form 15 for 11 form 32 is 12 of 14 exposure 13 research 14 exposure 15 for 26 and 16 most 18 students 17 medical 18 students 18 students 20 and 19 , 20 and 20 and 22 summer 20 and 26 and 21 the 22 summer 22 summer 23 between 23 between 25 first 24 their 25 first 26 and 28 years 26 and 29 of 27 second 28 years 29 of 31 school 30 medical 31 school 32 is 33 generally 32 is 36 period 34 the 35 longest 34 the 36 period 36 period 37 they 36 period 39 devote 37 they 38 can 38 can 39 devote 39 devote 40 solely 40 solely 41 to 41 to 42 research the goal of short - term training programs is to whet the students ' appetite for research and spark their interest in the field . 0 ###LEFT-WALL### 2 goal 0 ###LEFT-WALL### 25 . 1 the 2 goal 2 goal 3 of 2 goal 9 is 3 of 8 programs 4 short 5 - 4 short 6 term 6 term 8 programs 7 training 8 programs 9 is 10 to 9 is 18 and 10 to 18 and 11 whet 15 appetite 11 whet 18 and 12 the 13 students 13 students 14 ' 14 ' 15 appetite 15 appetite 16 for 16 for 17 research 18 and 19 spark 19 spark 21 interest 19 spark 22 in 20 their 21 interest 22 in 24 field 23 the 24 field relatively little research has been done to test the effectiveness of short - term research training programs . 0 ###LEFT-WALL### 3 research 0 ###LEFT-WALL### 5 been 0 ###LEFT-WALL### 18 . 1 relatively 2 little 2 little 3 research 3 research 4 has 4 has 5 been 5 been 6 done 6 done 7 to 7 to 8 test 8 test 10 effectiveness 9 the 10 effectiveness 10 effectiveness 11 of 10 effectiveness 16 training 11 of 15 research 12 short 13 - 12 short 14 term 14 term 15 research 16 training 17 programs in an effort to examine short - term effects of three different nih - funded summer research training programs for medical students , we assessed the trainees ['] ( n = 75 ) research self - efficacy prior [to] and [after] the programs using [an] 11 - item scale . 0 ###LEFT-WALL### 6 short 0 ###LEFT-WALL### 7 - 1 in 3 effort 1 in 6 short 2 an 3 effort 3 effort 4 to 3 effort 5 examine 4 to 5 examine 7 - 9 effects 7 - 14 - 8 term 9 effects 9 effects 10 of 10 of 13 nih 11 three 13 nih 12 different 13 nih 14 - 18 training 14 - 19 programs 14 - 23 , 15 funded 16 summer 16 summer 17 research 17 research 18 training 18 training 19 programs 19 programs 20 for 20 for 22 students 21 medical 22 students 23 , 24 we 24 we 25 assessed 25 assessed 27 trainees 25 assessed 34 research 26 the 27 trainees 27 trainees 31 = 27 trainees 34 research 29 ( 31 = 30 n 31 = 31 = 32 75 31 = 33 ) 34 research 35 self 35 self 40 and 36 - 40 and 37 efficacy 38 prior 38 prior 40 and 40 and 43 programs 40 and 49 scale 40 and 50 . 42 the 43 programs 43 programs 44 using 44 using 46 11 47 - 49 scale 48 item 49 scale 49 scale 50 . these hands - on training programs combined experiential , didactic , and mentoring elements . 0 ###LEFT-WALL### 2 hands 0 ###LEFT-WALL### 3 - 1 these 2 hands 3 - 6 programs 3 - 7 combined 3 - 15 . 4 on 5 training 4 on 6 programs 6 programs 7 combined 7 combined 14 elements 8 experiential 9 , 9 , 10 didactic 9 , 12 and 11 , 12 and 12 and 13 mentoring 12 and 14 elements the students demonstrated a significant increase in their self - efficacy for research . 0 ###LEFT-WALL### 2 students 0 ###LEFT-WALL### 3 demonstrated 0 ###LEFT-WALL### 10 - 0 ###LEFT-WALL### 14 . 1 the 2 students 2 students 3 demonstrated 3 demonstrated 6 increase 3 demonstrated 7 in 4 a 5 significant 4 a 6 increase 5 significant 6 increase 7 in 9 self 8 their 9 self 10 - 11 efficacy 11 efficacy 12 for 12 for 13 research trainees ' gender , ranking of their school , type of research , and specific content of research project did not predict improvement . 0 ###LEFT-WALL### 3 gender 0 ###LEFT-WALL### 4 , 0 ###LEFT-WALL### 24 . 1 trainees 2 ' 2 ' 3 gender 4 , 5 ranking 4 , 22 predict 5 ranking 6 of 5 ranking 20 did 6 of 19 project 7 their 19 project 8 school 9 , 9 , 11 of 9 , 14 and 10 type 11 of 11 of 12 research 13 , 14 and 14 and 16 content 14 and 17 of 14 and 19 project 15 specific 16 content 17 of 18 research 20 did 21 not 20 did 22 predict 22 predict 23 improvement effect sizes for different types of items on the scale varied , with the largest gain seen in research methodology and communication of study findings . 0 ###LEFT-WALL### 1 effect 1 effect 2 sizes 1 effect 3 for 1 effect 8 on 3 for 7 items 4 different 5 types 5 types 6 of 5 types 7 items 6 of 7 items 8 on 10 scale 9 the 10 scale 10 scale 11 varied 11 varied 13 with 12 , 13 with 13 with 21 and 13 with 26 . 14 the 15 largest 14 the 16 gain 16 gain 17 seen 16 gain 18 in 16 gain 21 and 18 in 20 methodology 19 research 20 methodology 21 and 22 communication 21 and 23 of 23 of 25 findings 24 study 25 findings reductions in skeletal muscle function [occur] during the course of healthy aging as well as with bed rest or diverse diseases such as cancer , muscular dystrophy , and heart failure . 0 ###LEFT-WALL### 1 reductions 0 ###LEFT-WALL### 5 function 0 ###LEFT-WALL### 32 . 1 reductions 2 in 1 reductions 5 function 2 in 4 muscle 3 skeletal 4 muscle 5 function 7 during 5 function 14 well 5 function 15 as 5 function 23 as 7 during 9 course 8 the 9 course 9 course 10 of 10 of 12 aging 11 healthy 12 aging 13 as 14 well 15 as 16 with 16 with 19 or 17 bed 18 rest 18 rest 19 or 19 or 21 diseases 20 diverse 21 diseases 22 such 23 as 23 as 29 and 24 cancer 25 , 25 , 27 dystrophy 25 , 29 and 26 muscular 27 dystrophy 28 , 29 and 29 and 31 failure 30 heart 31 failure however , there are no accepted pharmacologic therapies to improve impaired skeletal muscle [function] . 0 ###LEFT-WALL### 3 there 0 ###LEFT-WALL### 4 are 0 ###LEFT-WALL### 15 . 1 however 2 , 1 however 3 there 3 there 4 are 4 are 8 therapies 4 are 9 to 5 no 8 therapies 6 accepted 8 therapies 7 pharmacologic 8 therapies 9 to 10 improve 10 improve 13 muscle 11 impaired 13 muscle 12 skeletal 13 muscle nitric oxide may influence skeletal muscle function through effects on excitation - contraction coupling , myofibrillar function , perfusion , and metabolism . 0 ###LEFT-WALL### 2 oxide 0 ###LEFT-WALL### 4 influence 0 ###LEFT-WALL### 12 - 1 nitric 2 oxide 2 oxide 3 may 3 may 4 influence 4 influence 9 effects 4 influence 10 on 5 skeletal 6 muscle 6 muscle 9 effects 7 function 9 effects 8 through 9 effects 10 on 11 excitation 12 - 14 coupling 12 - 15 , 12 - 23 . 13 contraction 14 coupling 15 , 17 function 15 , 18 , 16 myofibrillar 17 function 18 , 21 and 19 perfusion 21 and 20 , 21 and 21 and 22 metabolism here we show that augmentation of nitric oxide - cyclic guanosine monophosphate signaling by short - term daily administration of the phosphodiesterase 5 inhibitor sildenafil increases protein synthesis , alters protein expression and nitrosylation , and reduces fatigue in human skeletal muscle . 0 ###LEFT-WALL### 2 we 0 ###LEFT-WALL### 3 show 0 ###LEFT-WALL### 9 - 0 ###LEFT-WALL### 43 . 1 here 2 we 2 we 3 show 3 show 4 that 3 show 5 augmentation 5 augmentation 6 of 6 of 8 oxide 7 nitric 8 oxide 9 - 12 monophosphate 9 - 29 , 10 cyclic 12 monophosphate 11 guanosine 12 monophosphate 12 monophosphate 13 signaling 12 monophosphate 14 by 12 monophosphate 29 , 14 by 19 administration 15 short 16 - 15 short 17 term 17 term 18 daily 18 daily 19 administration 19 administration 20 of 20 of 25 sildenafil 21 the 25 sildenafil 22 phosphodiesterase 23 5 22 phosphodiesterase 25 sildenafil 24 inhibitor 25 sildenafil 26 increases 28 synthesis 26 increases 29 , 27 protein 28 synthesis 29 , 36 and 29 , 39 in 30 alters 33 and 30 alters 36 and 31 protein 32 expression 32 expression 33 and 33 and 34 nitrosylation 35 , 36 and 36 and 37 reduces 37 reduces 38 fatigue 39 in 42 muscle 40 human 42 muscle 41 skeletal 42 muscle these findings suggest that phosphodiesterase 5 inhibitors represent viable pharmacologic interventions to improve muscle function . 0 ###LEFT-WALL### 2 findings 0 ###LEFT-WALL### 3 suggest 0 ###LEFT-WALL### 16 . 1 these 2 findings 2 findings 3 suggest 3 suggest 4 that 4 that 5 phosphodiesterase 4 that 15 function 5 phosphodiesterase 6 5 5 phosphodiesterase 7 inhibitors 5 phosphodiesterase 8 represent 7 inhibitors 8 represent 8 represent 11 interventions 8 represent 12 to 9 viable 11 interventions 10 pharmacologic 11 interventions 12 to 13 improve 13 improve 14 muscle the mri technique diffusion tensor imaging ( dti ) is reviewed along with microstructural changes associated with prodromal alzheimer 's disease ( ad ) as a potential biomarker for clinical applications . 0 ###LEFT-WALL### 6 imaging 0 ###LEFT-WALL### 11 reviewed 0 ###LEFT-WALL### 32 . 1 the 6 imaging 2 mri 6 imaging 3 technique 6 imaging 4 diffusion 6 imaging 5 tensor 6 imaging 6 imaging 8 dti 6 imaging 10 is 7 ( 8 dti 8 dti 9 ) 10 is 11 reviewed 11 reviewed 13 with 11 reviewed 17 with 11 reviewed 25 as 12 along 13 with 13 with 15 changes 14 microstructural 15 changes 15 changes 16 associated 17 with 21 disease 18 prodromal 19 alzheimer 19 alzheimer 20 's 20 's 21 disease 21 disease 23 ad 22 ( 23 ad 23 ad 24 ) 25 as 27 potential 26 a 27 potential 27 potential 28 biomarker 28 biomarker 29 for 29 for 31 applications 30 clinical 31 applications the prodromal stage of ad is characterized by mild cognitive impairment ( mci ) , representing a transitional state between normal aging and ad . 0 ###LEFT-WALL### 3 stage 0 ###LEFT-WALL### 7 characterized 1 the 3 stage 2 prodromal 3 stage 3 stage 4 of 3 stage 6 is 4 of 5 ad 6 is 7 characterized 7 characterized 8 by 7 characterized 16 representing 8 by 11 impairment 9 mild 11 impairment 10 cognitive 11 impairment 11 impairment 13 mci 12 ( 13 mci 13 mci 14 ) 15 , 16 representing 16 representing 19 state 16 representing 20 between 16 representing 25 . 17 a 18 transitional 17 a 19 state 18 transitional 19 state 20 between 23 and 21 normal 22 aging 22 aging 23 and 23 and 24 ad microstructural abnormalities on dti are promising in vivo biomarkers of gray and white matter changes associated with the progression of ad pathology . 0 ###LEFT-WALL### 1 microstructural 0 ###LEFT-WALL### 16 associated 0 ###LEFT-WALL### 23 . 1 microstructural 2 abnormalities 1 microstructural 9 biomarkers 1 microstructural 10 of 1 microstructural 16 associated 2 abnormalities 3 on 2 abnormalities 5 are 3 on 4 dti 5 are 6 promising 6 promising 8 vivo 6 promising 9 biomarkers 7 in 8 vivo 10 of 15 changes 11 gray 12 and 12 and 13 white 12 and 15 changes 14 matter 15 changes 16 associated 17 with 17 with 19 progression 18 the 19 progression 19 progression 20 of 20 of 22 pathology 21 ad 22 pathology elevated mean diffusivity and decreased fractional anisotropy are consistently found in prodromal ad , and even in cognitively normal elderly [who] progress to mci . 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 10 found 0 ###LEFT-WALL### 25 . 1 elevated 3 diffusivity 2 mean 3 diffusivity 3 diffusivity 4 and 4 and 7 anisotropy 4 and 8 are 5 decreased 7 anisotropy 6 fractional 7 anisotropy 8 are 10 found 9 consistently 10 found 10 found 15 and 10 found 23 to 11 in 13 ad 11 in 15 and 12 prodromal 13 ad 14 , 15 and 15 and 16 even 15 and 17 in 17 in 22 progress 18 cognitively 19 normal 19 normal 22 progress 20 elderly 22 progress 23 to 24 mci however , quality of parameter maps may be affected by artifacts of motion , susceptibility , and eddy current - induced distortions . 0 ###LEFT-WALL### 3 quality 0 ###LEFT-WALL### 9 affected 0 ###LEFT-WALL### 20 - 1 however 2 , 1 however 3 quality 3 quality 4 of 3 quality 7 may 4 of 6 maps 5 parameter 6 maps 7 may 8 be 8 be 9 affected 9 affected 10 by 9 affected 19 current 10 by 11 artifacts 11 artifacts 12 of 12 of 17 and 13 motion 14 , 14 , 15 susceptibility 14 , 17 and 16 , 17 and 17 and 18 eddy 20 - 22 distortions 20 - 23 . 21 induced 22 distortions the dti maps are typically analyzed [by] [region] - of - interest or voxel - based analytic techniques such as tract [-] based spatial statistics . 0 ###LEFT-WALL### 2 dti 0 ###LEFT-WALL### 16 based 0 ###LEFT-WALL### 26 . 1 the 2 dti 2 dti 3 maps 2 dti 10 of 2 dti 13 or 2 dti 16 based 3 maps 4 are 4 are 5 typically 4 are 10 of 5 typically 6 analyzed 6 analyzed 9 - 11 - 13 or 12 interest 13 or 13 or 14 voxel 13 or 15 - 16 based 18 techniques 17 analytic 18 techniques 18 techniques 20 as 19 such 20 as 20 as 25 statistics 21 tract 23 based 23 based 25 statistics 24 spatial 25 statistics dti - based index [of] diffusivity is complementary to macrostructural gray matter changes in the hippocampus in detecting prodromal ad . 0 ###LEFT-WALL### 1 dti 0 ###LEFT-WALL### 2 - 0 ###LEFT-WALL### 21 . 2 - 6 diffusivity 2 - 7 is 3 based 4 index 4 index 6 diffusivity 6 diffusivity 7 is 7 is 8 complementary 8 complementary 9 to 8 complementary 14 in 8 complementary 17 in 9 to 13 changes 10 macrostructural 12 matter 11 gray 12 matter 12 matter 13 changes 14 in 16 hippocampus 15 the 16 hippocampus 17 in 18 detecting 18 detecting 20 ad 19 prodromal 20 ad breakdown of structural connectivity measured with dti may impact cognitive performance during early ad . 0 ###LEFT-WALL### 1 breakdown 0 ###LEFT-WALL### 9 impact 0 ###LEFT-WALL### 15 . 1 breakdown 2 of 1 breakdown 8 may 2 of 4 connectivity 3 structural 4 connectivity 4 connectivity 5 measured 5 measured 6 with 6 with 7 dti 8 may 9 impact 9 impact 11 performance 9 impact 12 during 10 cognitive 11 performance 12 during 14 ad 13 early 14 ad furthermore , assessment of hippocampal connections may help in understanding the cerebral organization and remodeling associated with treatment response . 0 ###LEFT-WALL### 3 assessment 0 ###LEFT-WALL### 8 help 0 ###LEFT-WALL### 20 . 1 furthermore 2 , 1 furthermore 3 assessment 3 assessment 4 of 3 assessment 7 may 4 of 6 connections 5 hippocampal 6 connections 7 may 8 help 8 help 9 in 9 in 10 understanding 10 understanding 19 response 11 the 19 response 12 cerebral 13 organization 13 organization 14 and 14 and 15 remodeling 14 and 16 associated 14 and 19 response 16 associated 17 with 17 with 18 treatment objective : the prevalence of chronic pain ranges from 40 % to 80 % in long - term care facilities , and it is especially high among older adults who are unable to communicate due to cognitive impairments . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 2 : 4 prevalence 2 : 24 is 2 : 39 . 3 the 4 prevalence 4 prevalence 5 of 4 prevalence 15 in 4 prevalence 24 is 5 of 8 ranges 6 chronic 7 pain 7 pain 8 ranges 8 ranges 9 from 9 from 11 % 10 40 11 % 11 % 12 to 12 to 14 % 13 80 14 % 15 in 22 and 16 long 17 - 16 long 18 term 18 term 20 facilities 19 care 20 facilities 20 facilities 22 and 21 , 22 and 22 and 23 it 24 is 25 especially 24 is 26 high 26 high 27 among 26 high 33 to 26 high 34 communicate 27 among 29 adults 28 older 29 adults 29 adults 30 who 29 adults 31 are 30 who 31 are 31 are 32 unable 33 to 34 communicate 34 communicate 36 to 35 due 36 to 36 to 38 impairments 37 cognitive 38 impairments although validated assessment tools exist , pain detection in this population is often done by interdisciplinary evaluation [(] ie [ )(, which largely relies on the subjective impression of health care providers . 0 ###LEFT-WALL### 4 tools 0 ###LEFT-WALL### 5 exist 0 ###LEFT-WALL### 6 , 0 ###LEFT-WALL### 33 . 1 although 3 assessment 1 although 4 tools 2 validated 3 assessment 4 tools 5 exist 6 , 8 detection 6 , 12 is 6 , 21 )(, 7 pain 8 detection 8 detection 9 in 8 detection 12 is 9 in 11 population 10 this 11 population 12 is 14 done 13 often 14 done 14 done 15 by 15 by 19 ie 16 interdisciplinary 17 evaluation 17 evaluation 19 ie 21 )(, 22 which 21 )(, 24 relies 22 which 24 relies 23 largely 24 relies 24 relies 25 on 25 on 28 impression 26 the 28 impression 27 subjective 28 impression 28 impression 29 of 29 of 32 providers 30 health 32 providers 31 care 32 providers the aim of this study was to examine the agreement between the ie and validated observational pain tools . 0 ###LEFT-WALL### 2 aim 0 ###LEFT-WALL### 14 and 0 ###LEFT-WALL### 19 . 1 the 2 aim 2 aim 3 of 2 aim 14 and 3 of 5 study 4 this 5 study 6 was 7 to 6 was 8 examine 6 was 14 and 7 to 8 examine 8 examine 10 agreement 8 examine 11 between 9 the 10 agreement 11 between 13 ie 12 the 13 ie 14 and 15 validated 14 and 18 tools 16 observational 17 pain 17 pain 18 tools setting : we recruited 59 residents with limited ability to communicate . 0 ###LEFT-WALL### 1 setting 0 ###LEFT-WALL### 2 : 2 : 3 we 2 : 4 recruited 2 : 12 . 3 we 4 recruited 4 recruited 6 residents 4 recruited 7 with 5 59 6 residents 7 with 9 ability 8 limited 9 ability 9 ability 10 to 9 ability 11 communicate 10 to 11 communicate the pain behaviors of each participant were assessed with two validated tools , the pain assessment checklist for seniors with limited ability to communicate ( pacslac ) and the pain assessment in advanced dementia ( painad ) , during transfer or mobilization . 0 ###LEFT-WALL### 3 behaviors 0 ###LEFT-WALL### 8 assessed 0 ###LEFT-WALL### 13 , 0 ###LEFT-WALL### 43 . 1 the 3 behaviors 2 pain 3 behaviors 3 behaviors 4 of 3 behaviors 7 were 4 of 6 participant 5 each 6 participant 7 were 8 assessed 8 assessed 9 with 9 with 12 tools 10 two 12 tools 11 validated 12 tools 13 , 28 and 14 the 17 checklist 15 pain 16 assessment 16 assessment 17 checklist 17 checklist 18 for 17 checklist 20 with 17 checklist 28 and 18 for 19 seniors 20 with 22 ability 21 limited 22 ability 22 ability 23 to 23 to 24 communicate 24 communicate 26 pacslac 25 ( 26 pacslac 26 pacslac 27 ) 28 and 31 assessment 28 and 38 , 28 and 39 during 29 the 31 assessment 30 pain 31 assessment 31 assessment 32 in 32 in 36 painad 33 advanced 34 dementia 34 dementia 36 painad 35 ( 36 painad 36 painad 37 ) 39 during 41 or 40 transfer 41 or 41 or 42 mobilization the results were then compared with the findings of the ie . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 5 compared 0 ###LEFT-WALL### 12 . 1 the 2 results 2 results 3 were 3 were 4 then 3 were 5 compared 5 compared 6 with 6 with 8 findings 7 the 8 findings 8 findings 9 of 9 of 11 ie 10 the 11 ie results : the correlation between the pacslac and painad was high ( r = 0.79 [ 95 % ci : [0.67] - 0.87 ] ) . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 4 correlation 2 : 10 was 2 : 26 . 3 the 4 correlation 4 correlation 5 between 4 correlation 10 was 5 between 9 painad 6 the 9 painad 7 pacslac 8 and 8 and 9 painad 10 was 11 high 11 high 14 = 12 ( 14 = 13 r 14 = 14 = 15 0.79 15 0.79 18 % 16 [ 18 % 17 95 18 % 18 % 19 ci 18 % 20 : 18 % 23 0.87 18 % 25 ) 19 ci 20 : 22 - 23 0.87 23 0.87 24 ] however , we found a low [to] moderate association between the pacslac and the ie ( r = 0.34 [ 95 % ci : 0.09 - 0.55 ] [ )(, and a weaker association was observed between the painad and the ie ( r = 0.25 [ 95 % ci : - 0.02 - 0.48 ] ) . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 24 : 1 however 2 , 1 however 3 we 3 we 4 found 4 found 9 association 5 a 6 low 5 a 9 association 6 low 9 association 8 moderate 9 association 9 association 10 between 10 between 13 and 11 the 12 pacslac 12 pacslac 13 and 13 and 15 ie 13 and 18 = 13 and 23 ci 14 the 15 ie 16 ( 18 = 17 r 18 = 18 = 19 0.34 20 [ 23 ci 21 95 23 ci 22 % 23 ci 23 ci 24 : 24 : 25 0.09 24 : 31 and 25 0.09 27 0.55 26 - 27 0.55 27 0.55 28 ] 30 )(, 31 and 31 and 34 association 31 and 36 observed 32 a 34 association 33 weaker 34 association 34 association 35 was 35 was 36 observed 36 observed 37 between 37 between 40 and 38 the 39 painad 39 painad 40 and 40 and 42 ie 40 and 45 = 40 and 48 95 41 the 42 ie 43 ( 45 = 44 r 45 = 45 = 46 0.25 47 [ 48 95 48 95 50 ci 48 95 51 : 48 95 53 0.02 48 95 58 . 49 % 50 ci 50 ci 51 : 52 - 53 0.02 53 0.02 55 0.48 53 0.02 57 ) 54 - 55 0.48 55 0.48 56 ] when the ie concluded that there was an absence of pain behavior , the painad and the pacslac detected the presence of pain in 13.6 [%] and 27.1 % of the cases respectively . 0 ###LEFT-WALL### 6 there 0 ###LEFT-WALL### 7 was 0 ###LEFT-WALL### 13 , 0 ###LEFT-WALL### 34 . 1 when 3 ie 1 when 4 concluded 1 when 6 there 2 the 3 ie 3 ie 4 concluded 4 concluded 5 that 6 there 7 was 7 was 9 absence 8 an 9 absence 9 absence 10 of 10 of 12 behavior 11 pain 12 behavior 13 , 15 painad 13 , 16 and 14 the 15 painad 16 and 18 pacslac 16 and 19 detected 17 the 18 pacslac 18 pacslac 19 detected 19 detected 21 presence 19 detected 33 respectively 20 the 21 presence 21 presence 22 of 22 of 23 pain 23 pain 24 in 23 pain 30 of 24 in 29 % 25 13.6 27 and 27 and 28 27.1 27 and 29 % 30 of 32 cases 31 the 32 cases conclusion : these results may be explained by an inability of ie to assess pain correctly or by instruments providing false positive results . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 7 explained 0 ###LEFT-WALL### 24 . 2 : 6 be 3 these 4 results 4 results 5 may 5 may 6 be 6 be 7 explained 7 explained 17 or 8 by 10 inability 8 by 17 or 9 an 10 inability 10 inability 11 of 10 inability 13 to 10 inability 14 assess 11 of 12 ie 13 to 14 assess 14 assess 15 pain 14 assess 16 correctly 17 or 18 by 18 by 19 instruments 19 instruments 20 providing 20 providing 23 results 21 false 23 results 22 positive 23 results nevertheless , as detection of pain is difficult in this population , our research supports the use of validated tools to complement assessment of pain by the ie and make sure that no pain goes undetected . 0 ###LEFT-WALL### 14 research 0 ###LEFT-WALL### 15 supports 0 ###LEFT-WALL### 37 . 1 nevertheless 2 , 1 nevertheless 14 research 3 as 4 detection 3 as 7 is 3 as 12 , 3 as 14 research 4 detection 5 of 4 detection 7 is 5 of 6 pain 7 is 8 difficult 8 difficult 9 in 9 in 11 population 10 this 11 population 13 our 14 research 14 research 15 supports 15 supports 17 use 15 supports 21 to 16 the 17 use 17 use 18 of 18 of 20 tools 19 validated 20 tools 21 to 29 and 22 complement 23 assessment 22 complement 26 by 22 complement 29 and 23 assessment 24 of 24 of 25 pain 26 by 28 ie 27 the 28 ie 29 and 30 make 30 make 31 sure 31 sure 32 that 32 that 34 pain 32 that 35 goes 33 no 34 pain 34 pain 35 goes 35 goes 36 undetected background : despite the advances in our understanding of aging - associated behavioral decline , relatively little is known about how aging affects neural circuits that regulate specific behaviors , particularly the expression of genes in specific neural circuits during aging . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 11 - 1 background 2 : 2 : 3 despite 2 : 6 in 3 despite 5 advances 4 the 5 advances 6 in 8 understanding 7 our 8 understanding 8 understanding 9 of 9 of 10 aging 11 - 14 decline 11 - 15 , 12 associated 14 decline 13 behavioral 14 decline 15 , 17 little 15 , 19 known 16 relatively 17 little 17 little 18 is 18 is 19 known 19 known 20 about 20 about 21 how 21 how 22 aging 21 how 23 affects 22 aging 23 affects 23 affects 25 circuits 24 neural 25 circuits 25 circuits 26 that 25 circuits 27 regulate 25 circuits 33 expression 26 that 27 regulate 27 regulate 29 behaviors 28 specific 29 behaviors 30 , 31 particularly 30 , 33 expression 32 the 33 expression 33 expression 34 of 33 expression 36 in 33 expression 42 . 34 of 35 genes 36 in 39 circuits 37 specific 39 circuits 38 neural 39 circuits 39 circuits 40 during 40 during 41 aging we have addressed this by exploring a peptidergic neuron [r15] , an identified neuron of the marine snail aplysia californica . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 addressed 1 we 2 have 2 have 3 addressed 3 addressed 4 this 3 addressed 5 by 5 by 6 exploring 6 exploring 9 neuron 7 a 9 neuron 8 peptidergic 9 neuron 9 neuron 14 neuron 11 , 14 neuron 12 an 14 neuron 13 identified 14 neuron 14 neuron 15 of 14 neuron 21 . 15 of 20 californica 16 the 20 californica 17 marine 18 snail 18 snail 20 californica 19 aplysia 20 californica r15 is implicated in reproduction and osmoregulation and responds to neurotransmitters such as acetylcholine [,] serotonin and glutamate and is characterized by its action potential bursts . 0 ###LEFT-WALL### 1 r15 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 27 . 1 r15 8 and 2 is 3 implicated 2 is 8 and 3 implicated 4 in 4 in 6 and 5 reproduction 6 and 6 and 7 osmoregulation 8 and 9 responds 8 and 10 to 8 and 26 bursts 10 to 19 and 11 neurotransmitters 13 as 11 neurotransmitters 19 and 12 such 13 as 13 as 17 and 14 acetylcholine 16 serotonin 16 serotonin 17 and 17 and 18 glutamate 19 and 20 is 20 is 21 characterized 21 characterized 22 by 22 by 24 action 23 its 24 action 25 potential 26 bursts results : we examined changes in gene expression in r15 neurons during aging by microarray analyses of rnas from two different age groups , mature and old animals . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 3 we 2 : 4 examined 2 : 29 . 3 we 4 examined 4 examined 5 changes 4 examined 6 in 4 examined 14 by 6 in 8 expression 7 gene 8 expression 8 expression 9 in 8 expression 12 during 9 in 11 neurons 10 r15 11 neurons 12 during 13 aging 14 by 26 and 15 microarray 16 analyses 16 analyses 17 of 16 analyses 24 , 17 of 18 rnas 18 rnas 19 from 19 from 23 groups 20 two 23 groups 21 different 22 age 22 age 23 groups 24 , 25 mature 24 , 26 and 26 and 28 animals 27 old 28 animals specifically we find that 1083 ests are differentially regulated in mature and old r15 neurons . 0 ###LEFT-WALL### 2 we 0 ###LEFT-WALL### 3 find 0 ###LEFT-WALL### 16 . 1 specifically 2 we 2 we 3 find 3 find 4 that 4 that 6 ests 4 that 9 regulated 5 1083 6 ests 6 ests 7 are 7 are 8 differentially 7 are 9 regulated 9 regulated 10 in 10 in 15 neurons 11 mature 12 and 12 and 13 old 12 and 15 neurons 14 r15 15 neurons bioinformatics analyses of these genes have identified specific biological pathways that are up or downregulated in mature and old neurons . 0 ###LEFT-WALL### 2 analyses 0 ###LEFT-WALL### 14 or 0 ###LEFT-WALL### 21 . 1 bioinformatics 2 analyses 2 analyses 3 of 2 analyses 6 have 3 of 5 genes 4 these 5 genes 6 have 14 or 7 identified 10 pathways 7 identified 14 or 8 specific 10 pathways 9 biological 10 pathways 10 pathways 11 that 10 pathways 12 are 11 that 12 are 12 are 13 up 14 or 15 downregulated 14 or 16 in 16 in 20 neurons 17 mature 18 and 18 and 19 old 18 and 20 neurons furthermore , qpcr analysis of single r15 neurons to quantify expression levels of candidate regulators involved in transcription ( creb1 ) and translation ( s6k ) showed that aging is associated with a decrease in expression of these regulators , and similar analysis in three other neurons ( l7 , l11 and r2 ) showed that gene expression change during aging could be bidirectional . 0 ###LEFT-WALL### 4 analysis 0 ###LEFT-WALL### 8 neurons 0 ###LEFT-WALL### 65 . 1 furthermore 2 , 1 furthermore 4 analysis 3 qpcr 4 analysis 4 analysis 5 of 4 analysis 8 neurons 5 of 7 r15 6 single 7 r15 8 neurons 9 to 8 neurons 32 with 9 to 10 quantify 10 quantify 12 levels 11 expression 12 levels 12 levels 13 of 12 levels 22 and 12 levels 27 showed 13 of 14 candidate 15 regulators 16 involved 15 regulators 17 in 15 regulators 22 and 17 in 18 transcription 18 transcription 20 creb1 19 ( 20 creb1 20 creb1 21 ) 22 and 23 translation 22 and 25 s6k 22 and 27 showed 24 ( 25 s6k 25 s6k 26 ) 27 showed 28 that 28 that 29 aging 28 that 31 associated 29 aging 30 is 30 is 31 associated 32 with 41 and 33 a 34 decrease 34 decrease 35 in 34 decrease 37 of 34 decrease 41 and 35 in 36 expression 37 of 39 regulators 38 these 39 regulators 40 , 41 and 41 and 43 analysis 41 and 44 in 42 similar 43 analysis 44 in 45 three 45 three 47 neurons 45 three 55 showed 46 other 47 neurons 47 neurons 49 l7 47 neurons 55 showed 48 ( 49 l7 49 l7 52 and 49 l7 54 ) 50 , 52 and 51 l11 52 and 52 and 53 r2 52 and 54 ) 55 showed 56 that 56 that 59 change 56 that 63 be 57 gene 58 expression 58 expression 59 change 59 change 60 during 59 change 62 could 60 during 61 aging 62 could 63 be 63 be 64 bidirectional conclusions : we find that aging is associated with bidirectional changes in gene expression . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 3 we 2 : 4 find 2 : 15 . 3 we 4 find 4 find 5 that 5 that 6 aging 5 that 8 associated 6 aging 7 is 7 is 8 associated 8 associated 9 with 8 associated 12 in 9 with 11 changes 10 bidirectional 11 changes 12 in 14 expression 13 gene 14 expression detailed bioinformatics analyses and human homolog searches have identified specific biological processes and human - relevant signaling pathways in r15 that are affected during aging . 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 9 identified 0 ###LEFT-WALL### 26 . 1 detailed 2 bioinformatics 2 bioinformatics 3 analyses 3 analyses 4 and 4 and 7 searches 4 and 8 have 5 human 7 searches 6 homolog 7 searches 8 have 9 identified 9 identified 13 and 10 specific 12 processes 11 biological 12 processes 12 processes 13 and 13 and 18 pathways 13 and 19 in 13 and 21 that 13 and 22 are 14 human 15 - 14 human 18 pathways 16 relevant 18 pathways 17 signaling 18 pathways 19 in 20 r15 21 that 22 are 22 are 23 affected 23 affected 24 during 24 during 25 aging evaluation of gene expression changes in different neurons suggests specific transcriptomic signature [of] single neurons during aging . 0 ###LEFT-WALL### 1 evaluation 0 ###LEFT-WALL### 9 suggests 0 ###LEFT-WALL### 18 . 1 evaluation 2 of 1 evaluation 9 suggests 2 of 5 changes 3 gene 5 changes 4 expression 5 changes 5 changes 6 in 6 in 8 neurons 7 different 8 neurons 9 suggests 15 neurons 9 suggests 16 during 10 specific 12 signature 11 transcriptomic 12 signature 12 signature 15 neurons 14 single 15 neurons 16 during 17 aging intact [epidermal] [barrier] [function] is crucial for survival and is associated with the presence of gradients of both calcium ion concentration and electric potential . 0 ###LEFT-WALL### 1 intact 0 ###LEFT-WALL### 11 associated 0 ###LEFT-WALL### 25 . 1 intact 9 and 5 is 6 crucial 5 is 9 and 6 crucial 7 for 7 for 8 survival 9 and 10 is 10 is 11 associated 11 associated 12 with 12 with 14 presence 13 the 14 presence 14 presence 15 of 15 of 16 gradients 16 gradients 17 of 17 of 22 and 18 both 22 and 19 calcium 21 concentration 20 ion 21 concentration 21 concentration 22 and 22 and 24 potential 23 electric 24 potential although many molecules , including ion channels and pumps , are known to contribute to maintenance of these gradients , the mechanisms involved in epidermal calcium ion dynamics have not been clarified . 0 ###LEFT-WALL### 22 mechanisms 0 ###LEFT-WALL### 32 clarified 0 ###LEFT-WALL### 33 . 1 although 3 molecules 1 although 14 contribute 1 although 20 , 1 although 22 mechanisms 2 many 3 molecules 3 molecules 5 including 3 molecules 11 are 4 , 5 including 5 including 8 and 5 including 10 , 6 ion 7 channels 7 channels 8 and 8 and 9 pumps 11 are 12 known 12 known 13 to 13 to 14 contribute 14 contribute 15 to 15 to 16 maintenance 16 maintenance 17 of 17 of 19 gradients 18 these 19 gradients 21 the 22 mechanisms 22 mechanisms 23 involved 22 mechanisms 24 in 22 mechanisms 29 have 24 in 28 dynamics 25 epidermal 26 calcium 26 calcium 27 ion 27 ion 28 dynamics 29 have 30 not 29 have 31 been 31 been 32 clarified we have established that a variety of neurotransmitters and their receptors , originally found in the brain , are expressed in keratinocytes and [are] also associated with barrier homeostasis . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 established 0 ###LEFT-WALL### 30 . 1 we 2 have 2 have 3 established 3 established 4 that 4 that 9 and 4 that 19 are 5 a 6 variety 6 variety 7 of 6 variety 9 and 7 of 8 neurotransmitters 9 and 11 receptors 9 and 14 found 9 and 19 are 10 their 11 receptors 12 , 14 found 13 originally 14 found 14 found 15 in 14 found 18 , 15 in 17 brain 16 the 17 brain 19 are 23 and 20 expressed 21 in 20 expressed 23 and 21 in 22 keratinocytes 23 and 26 associated 23 and 27 with 25 also 26 associated 27 with 29 homeostasis 28 barrier 29 homeostasis moreover , keratinocytes and neurons show some similarities of electrochemical behaviour . 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 6 show 0 ###LEFT-WALL### 12 . 1 moreover 2 , 1 moreover 4 and 3 keratinocytes 4 and 4 and 5 neurons 4 and 6 show 6 show 8 similarities 7 some 8 similarities 8 similarities 9 of 9 of 11 behaviour 10 electrochemical 11 behaviour as mathematical modelling and computer simulation have been employed to understand electrochemical phenomena in brain science , we considered that a similar approach might be applicable to describe the dynamics of epidermal electrochemical phenomena associated with barrier homeostasis . 0 ###LEFT-WALL### 18 we 0 ###LEFT-WALL### 19 considered 0 ###LEFT-WALL### 39 . 1 as 4 and 1 as 9 employed 1 as 17 , 1 as 18 we 2 mathematical 3 modelling 2 mathematical 4 and 4 and 6 simulation 4 and 7 have 5 computer 6 simulation 7 have 8 been 8 been 9 employed 9 employed 10 to 9 employed 11 understand 10 to 11 understand 11 understand 13 phenomena 11 understand 14 in 12 electrochemical 13 phenomena 14 in 16 science 15 brain 16 science 18 we 19 considered 19 considered 20 that 20 that 23 approach 20 that 28 describe 21 a 22 similar 21 a 23 approach 22 similar 23 approach 23 approach 24 might 24 might 25 be 25 be 26 applicable 26 applicable 27 to 27 to 28 describe 28 describe 30 dynamics 29 the 30 dynamics 30 dynamics 31 of 30 dynamics 36 with 31 of 34 phenomena 32 epidermal 34 phenomena 33 electrochemical 34 phenomena 34 phenomena 35 associated 36 with 38 homeostasis 37 barrier 38 homeostasis such methodology would also be potentially useful to address a number of difficult problems in clinical dermatology , such as ageing and itching . 0 ###LEFT-WALL### 2 methodology 0 ###LEFT-WALL### 5 be 1 such 2 methodology 2 methodology 3 would 3 would 5 be 4 also 5 be 5 be 6 potentially 5 be 7 useful 7 useful 8 to 7 useful 9 address 8 to 9 address 9 address 14 problems 9 address 15 in 10 a 11 number 11 number 12 of 11 number 14 problems 12 of 14 problems 13 difficult 14 problems 15 in 17 dermatology 16 clinical 17 dermatology 17 dermatology 20 as 18 , 20 as 19 such 20 as 20 as 22 and 20 as 24 . 21 ageing 22 and 22 and 23 itching although this work is at a very early stage , in this essay , we discuss the background to our approach and we present some preliminary results of simulation of barrier recovery . 0 ###LEFT-WALL### 15 we 0 ###LEFT-WALL### 16 discuss 0 ###LEFT-WALL### 22 and 0 ###LEFT-WALL### 33 . 1 although 3 work 1 although 4 is 1 although 14 , 1 although 15 we 2 this 3 work 3 work 4 is 4 is 5 at 5 at 9 stage 6 a 7 very 6 a 9 stage 7 very 8 early 8 early 9 stage 9 stage 11 in 10 , 11 in 11 in 13 essay 11 in 14 , 12 this 13 essay 15 we 16 discuss 16 discuss 18 background 16 discuss 19 to 17 the 18 background 19 to 21 approach 20 our 21 approach 22 and 23 we 22 and 24 present 23 we 24 present 24 present 27 results 25 some 27 results 26 preliminary 27 results 27 results 28 of 28 of 29 simulation 29 simulation 30 of 30 of 32 recovery 31 barrier 32 recovery purpose : access , enrollment , and engagement with primary and specialty health care services present significant challenges for rural populations worldwide . 0 ###LEFT-WALL### 1 purpose 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 4 , 0 ###LEFT-WALL### 23 . 1 purpose 2 : 2 : 3 access 4 , 5 enrollment 4 , 7 and 6 , 7 and 7 and 8 engagement 7 and 15 services 8 engagement 9 with 8 engagement 15 services 9 with 11 and 10 primary 11 and 11 and 14 care 12 specialty 14 care 13 health 14 care 15 services 18 challenges 15 services 22 worldwide 16 present 18 challenges 17 significant 18 challenges 18 challenges 19 for 19 for 21 populations 20 rural 21 populations the alabama veterans rural health initiative evaluated an innovative outreach intervention combining motivational interviewing , patient navigation , and health services education to promote utilization of the united states veterans administration healthcare system ( va ) by veterans who live in rural locations . 0 ###LEFT-WALL### 6 initiative 0 ###LEFT-WALL### 7 evaluated 0 ###LEFT-WALL### 19 and 0 ###LEFT-WALL### 44 . 1 the 6 initiative 2 alabama 3 veterans 3 veterans 4 rural 4 rural 5 health 5 health 6 initiative 6 initiative 7 evaluated 7 evaluated 11 intervention 8 an 9 innovative 8 an 11 intervention 9 innovative 11 intervention 10 outreach 11 intervention 11 intervention 12 combining 12 combining 14 interviewing 13 motivational 14 interviewing 14 interviewing 17 navigation 15 , 17 navigation 16 patient 17 navigation 17 navigation 18 , 19 and 20 health 19 and 21 services 20 health 21 services 21 services 22 education 22 education 23 to 22 education 24 promote 23 to 24 promote 24 promote 25 utilization 24 promote 37 by 24 promote 41 in 25 utilization 26 of 26 of 35 va 27 the 35 va 28 united 29 states 29 states 30 veterans 30 veterans 31 administration 31 administration 32 healthcare 32 healthcare 33 system 33 system 35 va 34 ( 35 va 35 va 36 ) 37 by 38 veterans 38 veterans 39 who 38 veterans 40 live 39 who 40 live 41 in 43 locations 42 rural 43 locations methods : community outreach workers completed the intervention and assessment , enrolling veterans from 31 counties in a southern state . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 5 workers 2 : 6 completed 2 : 21 . 3 community 5 workers 4 outreach 5 workers 5 workers 6 completed 6 completed 9 and 6 completed 14 from 6 completed 17 in 7 the 8 intervention 8 intervention 9 and 9 and 10 assessment 9 and 11 , 9 and 12 enrolling 12 enrolling 13 veterans 14 from 16 counties 15 31 16 counties 17 in 20 state 18 a 19 southern 18 a 20 state 19 southern 20 state a total 203 participants were randomized to either an enhanced enrollment and engagement outreach condition ( eee , n = 101 ) or an administrative outreach ( ao , n = 102 ) condition . 0 ###LEFT-WALL### 2 total 0 ###LEFT-WALL### 6 randomized 0 ###LEFT-WALL### 35 . 1 a 2 total 2 total 4 participants 2 total 5 were 2 total 6 randomized 3 203 4 participants 4 participants 5 were 6 randomized 7 to 6 randomized 31 = 6 randomized 34 condition 7 to 23 or 8 either 23 or 9 an 11 enrollment 10 enhanced 11 enrollment 11 enrollment 12 and 12 and 15 condition 12 and 17 eee 12 and 23 or 13 engagement 15 condition 14 outreach 15 condition 16 ( 17 eee 17 eee 20 = 17 eee 22 ) 18 , 20 = 19 n 20 = 20 = 21 101 20 = 22 ) 23 or 26 outreach 23 or 28 ao 24 an 26 outreach 25 administrative 26 outreach 27 ( 28 ao 28 ao 29 , 29 , 31 = 30 n 31 = 31 = 32 102 31 = 33 ) findings : eee participants enrolled and attended va appointments at higher rates and within fewer days than those who received ao . 0 ###LEFT-WALL### 1 findings 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 22 . 1 findings 2 : 2 : 4 participants 3 eee 4 participants 4 participants 6 and 5 enrolled 6 and 6 and 7 attended 6 and 9 appointments 6 and 17 than 8 va 9 appointments 9 appointments 13 and 10 at 12 rates 10 at 13 and 11 higher 12 rates 13 and 14 within 14 within 16 days 15 fewer 16 days 17 than 18 those 18 those 19 who 18 those 20 received 19 who 20 received 20 received 21 ao eighty - seven percent of eee veterans attended an appointment within 6 months , compared to 58 % of ao veterans ( p < [.] 0001 ) . 0 ###LEFT-WALL### 4 percent 0 ###LEFT-WALL### 8 attended 0 ###LEFT-WALL### 28 . 1 eighty 2 - 2 - 3 seven 2 - 4 percent 4 percent 5 of 4 percent 8 attended 5 of 7 veterans 6 eee 7 veterans 8 attended 10 appointment 8 attended 11 within 9 an 10 appointment 11 within 13 months 12 6 13 months 13 months 15 compared 14 , 15 compared 15 compared 16 to 15 compared 27 ) 16 to 18 % 17 58 18 % 18 % 19 of 19 of 21 veterans 20 ao 21 veterans 21 veterans 24 < 22 ( 24 < 23 p 24 < 24 < 26 0001 24 < 27 ) the median time to first appointment was 12 days for the eee group and 98 days for the ao group ( p < [.] 0001 ) . 0 ###LEFT-WALL### 16 days 0 ###LEFT-WALL### 20 group 0 ###LEFT-WALL### 27 . 1 the 16 days 2 median 3 time 3 time 4 to 3 time 7 was 4 to 6 appointment 5 first 6 appointment 7 was 14 and 8 12 9 days 8 12 14 and 9 days 10 for 9 days 13 group 10 for 12 eee 11 the 12 eee 14 and 15 98 15 98 16 days 16 days 17 for 16 days 20 group 17 for 19 ao 18 the 19 ao 20 group 23 < 21 ( 23 < 22 p 23 < 23 < 25 0001 23 < 26 ) additionally , a race by outreach group interaction emerged : black and white individuals benefited equally from the eee intervention ; however , black individuals who received ao took significantly longer to attend appointments than their white counterparts . 0 ###LEFT-WALL### 4 race 0 ###LEFT-WALL### 9 emerged 0 ###LEFT-WALL### 10 : 1 additionally 2 , 1 additionally 4 race 3 a 4 race 4 race 5 by 4 race 9 emerged 5 by 8 interaction 6 outreach 8 interaction 7 group 8 interaction 10 : 14 individuals 10 : 15 benefited 10 : 21 ; 10 : 39 . 11 black 12 and 12 and 13 white 12 and 14 individuals 14 individuals 15 benefited 15 benefited 16 equally 15 benefited 17 from 15 benefited 20 intervention 17 from 19 eee 18 the 19 eee 21 ; 25 individuals 21 ; 29 took 22 however 23 , 22 however 25 individuals 24 black 25 individuals 25 individuals 26 who 25 individuals 27 received 25 individuals 29 took 26 who 27 received 27 received 28 ao 29 took 31 longer 29 took 32 to 29 took 35 than 30 significantly 31 longer 32 to 33 attend 33 attend 34 appointments 35 than 38 counterparts 36 their 38 counterparts 37 white 38 counterparts conclusions : results provide needed empirical support for a specific outreach intervention that speeds enrollment [and] engagement for rural individuals in va services . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 23 services 0 ###LEFT-WALL### 24 . 2 : 3 results 2 : 4 provide 3 results 4 provide 4 provide 7 support 4 provide 8 for 5 needed 7 support 6 empirical 7 support 8 for 11 outreach 9 a 11 outreach 10 specific 11 outreach 11 outreach 12 intervention 11 outreach 23 services 12 intervention 13 that 12 intervention 14 speeds 12 intervention 23 services 13 that 14 speeds 14 speeds 17 engagement 14 speeds 21 in 15 enrollment 17 engagement 17 engagement 18 for 18 for 20 individuals 19 rural 20 individuals 21 in 22 va planned interventions to improve service utilization should ameliorate ambivalence about accessing health care in addition to addressing traditional systems or environmental - level barriers . 0 ###LEFT-WALL### 2 interventions 0 ###LEFT-WALL### 13 care 0 ###LEFT-WALL### 25 . 1 planned 2 interventions 2 interventions 3 to 2 interventions 11 accessing 2 interventions 13 care 3 to 4 improve 4 improve 5 service 4 improve 10 about 5 service 6 utilization 5 service 8 ameliorate 6 utilization 7 should 7 should 8 ameliorate 8 ameliorate 9 ambivalence 10 about 11 accessing 11 accessing 12 health 13 care 14 in 13 care 16 to 14 in 15 addition 16 to 17 addressing 17 addressing 24 barriers 18 traditional 19 systems 19 systems 20 or 20 or 23 level 20 or 24 barriers 21 environmental 22 - 21 environmental 23 level infertility , spontaneous abortion and conception of trisomic offspring increase exponentially with age in mammals but in women there is [an] apparent acceleration in the rate from about age 37 . 0 ###LEFT-WALL### 5 and 0 ###LEFT-WALL### 10 increase 0 ###LEFT-WALL### 31 . 1 infertility 2 , 2 , 4 abortion 2 , 5 and 3 spontaneous 4 abortion 5 and 6 conception 5 and 7 of 5 and 10 increase 7 of 9 offspring 8 trisomic 9 offspring 10 increase 11 exponentially 10 increase 12 with 10 increase 14 in 10 increase 28 about 12 with 13 age 14 in 15 mammals 15 mammals 16 but 15 mammals 19 there 15 mammals 27 from 16 but 17 in 17 in 18 women 19 there 20 is 20 is 23 acceleration 20 is 24 in 20 is 27 from 22 apparent 23 acceleration 24 in 26 rate 25 the 26 rate 28 about 29 age 29 age 30 37 the problems mostly commonly occur when the ovarian pool of follicles is depleted to a critical level with age but [are] also found in low follicular reserve of other etiologies . 0 ###LEFT-WALL### 2 problems 0 ###LEFT-WALL### 5 occur 0 ###LEFT-WALL### 31 . 1 the 2 problems 2 problems 5 occur 3 mostly 5 occur 4 commonly 5 occur 5 occur 6 when 5 occur 24 in 6 when 9 pool 6 when 20 but 7 the 9 pool 8 ovarian 9 pool 9 pool 10 of 9 pool 20 but 10 of 11 follicles 12 is 13 depleted 12 is 20 but 13 depleted 14 to 13 depleted 18 with 14 to 17 level 15 a 16 critical 15 a 17 level 16 critical 17 level 18 with 19 age 20 but 23 found 22 also 23 found 24 in 27 reserve 25 low 27 reserve 26 follicular 27 reserve 27 reserve 28 of 28 of 30 etiologies 29 other 30 etiologies since recent clinical studies have indicated that dehydroepiandrosterone ( dhea ) supplementation may reverse the problem of oocyte quality , this review of the literature was undertaken in an attempt to find an explanation of why this is effective ? 0 ###LEFT-WALL### 20 , 0 ###LEFT-WALL### 40 ? 1 since 4 studies 1 since 6 indicated 1 since 20 , 2 recent 4 studies 3 clinical 4 studies 4 studies 5 have 5 have 6 indicated 6 indicated 7 that 7 that 12 supplementation 7 that 13 may 8 dehydroepiandrosterone 10 dhea 8 dehydroepiandrosterone 12 supplementation 9 ( 10 dhea 10 dhea 11 ) 12 supplementation 13 may 14 reverse 16 problem 14 reverse 20 , 15 the 16 problem 16 problem 17 of 17 of 19 quality 18 oocyte 19 quality 20 , 32 find 21 this 22 review 22 review 23 of 22 review 26 was 23 of 25 literature 24 the 25 literature 26 was 27 undertaken 27 undertaken 28 in 27 undertaken 31 to 28 in 30 attempt 29 an 30 attempt 31 to 32 find 32 find 34 explanation 33 an 34 explanation 34 explanation 35 of 35 of 36 why 36 why 37 this 36 why 38 is 37 this 38 is 38 is 39 effective in affected ovaries , oxygenation of follicular fluid is low , ultrastructural disturbances [especially] of mitochondria , occur in granulosa cells and oocytes , and considerable disturbances of meiosis occur . 0 ###LEFT-WALL### 5 oxygenation 0 ###LEFT-WALL### 9 is 0 ###LEFT-WALL### 17 , 0 ###LEFT-WALL### 31 . 1 in 3 ovaries 1 in 4 , 1 in 5 oxygenation 2 affected 3 ovaries 5 oxygenation 6 of 5 oxygenation 9 is 6 of 8 fluid 7 follicular 8 fluid 9 is 13 disturbances 10 low 11 , 10 low 13 disturbances 12 ultrastructural 13 disturbances 13 disturbances 15 of 15 of 16 mitochondria 17 , 18 occur 17 , 25 and 18 occur 19 in 19 in 22 and 20 granulosa 21 cells 21 cells 22 and 22 and 23 oocytes 24 , 25 and 25 and 27 disturbances 25 and 30 occur 26 considerable 27 disturbances 27 disturbances 28 of 27 disturbances 30 occur 28 of 29 meiosis there [is] , however , no evidence to date that primordial follicles are compromised . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 3 , 0 ###LEFT-WALL### 15 . 3 , 7 evidence 3 , 14 compromised 4 however 5 , 4 however 7 evidence 6 no 7 evidence 7 evidence 9 date 7 evidence 10 that 7 evidence 13 are 7 evidence 14 compromised 8 to 9 date 10 that 12 follicles 10 that 13 are 11 primordial 12 follicles 12 follicles 13 are in females with normal fertility , pre - antral ovarian theca cells respond to stimulation by inhibin b to provide androgen - based support for the developing follicle . 0 ###LEFT-WALL### 12 cells 0 ###LEFT-WALL### 13 respond 0 ###LEFT-WALL### 29 . 1 in 2 females 1 in 6 , 1 in 12 cells 2 females 3 with 3 with 5 fertility 4 normal 5 fertility 7 pre 8 - 7 pre 12 cells 9 antral 12 cells 10 ovarian 12 cells 11 theca 12 cells 12 cells 13 respond 13 respond 14 to 13 respond 19 to 14 to 15 stimulation 15 stimulation 16 by 16 by 17 inhibin 17 inhibin 18 b 19 to 20 provide 20 provide 24 support 20 provide 25 for 21 androgen 22 - 21 androgen 24 support 23 based 24 support 25 for 28 follicle 26 the 28 follicle 27 developing 28 follicle with depletion of follicle numbers , inhibin b is reduced with consequent reduction in theca dhea . 0 ###LEFT-WALL### 7 inhibin 0 ###LEFT-WALL### 10 reduced 0 ###LEFT-WALL### 17 . 1 with 2 depletion 1 with 6 , 1 with 7 inhibin 2 depletion 3 of 3 of 5 numbers 4 follicle 5 numbers 7 inhibin 8 b 7 inhibin 9 is 9 is 10 reduced 10 reduced 11 with 10 reduced 14 in 11 with 13 reduction 12 consequent 13 reduction 14 in 16 dhea 15 theca 16 dhea as well as inducing a plethora of deleterious changes in follicular cytoplasmic structure and function , the omega 9 palmitate/oleate ratio is increased by lowered activity of pparα . 0 ###LEFT-WALL### 21 ratio 0 ###LEFT-WALL### 23 increased 0 ###LEFT-WALL### 29 . 1 as 2 well 2 well 3 as 3 as 4 inducing 3 as 16 , 3 as 21 ratio 4 inducing 6 plethora 4 inducing 10 in 5 a 6 plethora 6 plethora 7 of 7 of 9 changes 8 deleterious 9 changes 10 in 14 and 11 follicular 13 structure 12 cytoplasmic 13 structure 13 structure 14 and 14 and 15 function 17 the 21 ratio 18 omega 21 ratio 19 9 21 ratio 20 palmitate/oleate 21 ratio 21 ratio 22 is 22 is 23 increased 23 increased 24 by 24 by 26 activity 25 lowered 26 activity 26 activity 27 of 27 of 28 pparα this provides conditions for increased ceramide synthesis and follicular loss through ceramide [-] induced apoptosis is accelerated . 0 ###LEFT-WALL### 1 this 0 ###LEFT-WALL### 2 provides 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 18 . 1 this 2 provides 2 provides 3 conditions 2 provides 4 for 4 for 7 synthesis 5 increased 6 ceramide 6 ceramide 7 synthesis 8 and 10 loss 8 and 17 accelerated 9 follicular 10 loss 10 loss 11 through 10 loss 16 is 11 through 15 apoptosis 12 ceramide 14 induced 14 induced 15 apoptosis 16 is 17 accelerated in humans critical theca dhea [synthesis] occurs at about 70 days prior to ovulation thus effective supplementation needs to be undertaken about four months prior to intended conception ; [timing] which is also suggested by successful interventions to date . 0 ###LEFT-WALL### 5 dhea 0 ###LEFT-WALL### 7 occurs 0 ###LEFT-WALL### 18 needs 0 ###LEFT-WALL### 29 ; 0 ###LEFT-WALL### 40 . 1 in 2 humans 1 in 5 dhea 3 critical 5 dhea 4 theca 5 dhea 5 dhea 7 occurs 7 occurs 8 at 8 at 11 days 9 about 10 70 10 70 11 days 11 days 17 supplementation 11 days 18 needs 12 prior 13 to 13 to 14 ovulation 13 to 17 supplementation 15 thus 17 supplementation 16 effective 17 supplementation 17 supplementation 18 needs 18 needs 19 to 18 needs 26 to 18 needs 29 ; 19 to 20 be 20 be 21 undertaken 21 undertaken 22 about 22 about 24 months 23 four 24 months 25 prior 26 to 26 to 28 conception 27 intended 28 conception 29 ; 31 which 29 ; 34 suggested 31 which 32 is 32 is 33 also 32 is 34 suggested 34 suggested 35 by 34 suggested 39 date 35 by 37 interventions 36 successful 37 interventions 38 to 39 date in humans and primates that undergo adrenarche , the adrenal zona reticularis ( zr ) is the major site of dhea production , however this is also reduced with age . 0 ###LEFT-WALL### 1 in 0 ###LEFT-WALL### 16 is 0 ###LEFT-WALL### 23 , 0 ###LEFT-WALL### 31 . 1 in 3 and 1 in 16 is 2 humans 3 and 3 and 4 primates 3 and 5 that 3 and 6 undergo 5 that 6 undergo 6 undergo 7 adrenarche 7 adrenarche 12 reticularis 8 , 12 reticularis 9 the 12 reticularis 10 adrenal 12 reticularis 11 zona 12 reticularis 12 reticularis 14 zr 12 reticularis 15 ) 13 ( 14 zr 14 zr 15 ) 16 is 19 site 17 the 19 site 18 major 19 site 19 site 20 of 20 of 22 production 21 dhea 22 production 23 , 25 this 23 , 28 reduced 24 however 25 this 25 this 26 is 26 is 27 also 26 is 28 reduced 28 reduced 29 with 29 with 30 age concomitant loss [in] [function] of the zr might account for the acceleration in the rate of aging seen in humans in the late thirties ' age group . 0 ###LEFT-WALL### 2 loss 0 ###LEFT-WALL### 9 account 0 ###LEFT-WALL### 28 . 1 concomitant 2 loss 2 loss 5 of 2 loss 8 might 5 of 7 zr 6 the 7 zr 8 might 9 account 9 account 10 for 9 account 19 in 10 for 12 acceleration 11 the 12 acceleration 12 acceleration 13 in 12 acceleration 16 of 12 acceleration 18 seen 13 in 15 rate 14 the 15 rate 16 of 17 aging 19 in 20 humans 20 humans 21 in 21 in 27 group 22 the 24 thirties 23 late 24 thirties 24 thirties 25 ' 25 ' 27 group 26 age 27 group sleep is an active state that plays an important role in the consolidation of memory . 0 ###LEFT-WALL### 1 sleep 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 16 . 1 sleep 2 is 2 is 5 state 3 an 4 active 3 an 5 state 4 active 5 state 5 state 6 that 5 state 7 plays 6 that 7 plays 7 plays 10 role 7 plays 11 in 8 an 9 important 8 an 10 role 9 important 10 role 11 in 13 consolidation 12 the 13 consolidation 13 consolidation 14 of 14 of 15 memory it has been found to enhance explicit memories in both adults and children . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 4 found 0 ###LEFT-WALL### 14 . 1 it 2 has 2 has 3 been 3 been 4 found 4 found 5 to 5 to 6 enhance 6 enhance 8 memories 6 enhance 9 in 7 explicit 8 memories 9 in 12 and 10 both 11 adults 11 adults 12 and 12 and 13 children however , in contrast to adults , children do not always show [a] sleep - related improvement in implicit learning . 0 ###LEFT-WALL### 8 children 0 ###LEFT-WALL### 12 show 0 ###LEFT-WALL### 16 related 1 however 2 , 1 however 8 children 2 , 3 in 3 in 4 contrast 3 in 7 , 3 in 8 children 4 contrast 5 to 5 to 6 adults 8 children 9 do 9 do 10 not 9 do 12 show 11 always 12 show 12 show 14 sleep 15 - 16 related 16 related 17 improvement 16 related 18 in 16 related 21 . 18 in 20 learning 19 implicit 20 learning the majority of research on sleep [-] dependent memory consolidation focuses on adults ; hence , the current study examined sleep - related effects on two tasks in children . 0 ###LEFT-WALL### 2 majority 0 ###LEFT-WALL### 11 focuses 0 ###LEFT-WALL### 14 ; 0 ###LEFT-WALL### 30 . 1 the 2 majority 2 majority 3 of 2 majority 5 on 2 majority 11 focuses 3 of 4 research 5 on 10 consolidation 6 sleep 8 dependent 8 dependent 10 consolidation 9 memory 10 consolidation 11 focuses 12 on 12 on 13 adults 14 ; 19 study 14 ; 20 examined 15 hence 16 , 15 hence 19 study 17 the 19 study 18 current 19 study 19 study 20 examined 20 examined 21 sleep 20 examined 27 tasks 21 sleep 27 tasks 22 - 23 related 23 related 24 effects 23 related 25 on 23 related 27 tasks 25 on 26 two 27 tasks 28 in 28 in 29 children thirty - three typically developing children aged 6 - 12 years took part in the study . 0 ###LEFT-WALL### 6 children 0 ###LEFT-WALL### 7 aged 0 ###LEFT-WALL### 17 . 1 thirty 2 - 2 - 3 three 2 - 6 children 4 typically 5 developing 5 developing 6 children 6 children 7 aged 7 aged 9 - 8 6 9 - 9 - 10 12 10 12 11 years 11 years 13 part 12 took 13 part 13 part 14 in 14 in 16 study 15 the 16 study actigraphy was used to monitor sleep . 0 ###LEFT-WALL### 1 actigraphy 0 ###LEFT-WALL### 3 used 0 ###LEFT-WALL### 7 . 1 actigraphy 2 was 2 was 3 used 3 used 4 to 3 used 5 monitor 4 to 5 monitor 5 monitor 6 sleep sleep - dependent memory consolidation was assessed using a novel [non] - word learning task and the tower of hanoi cognitive puzzle , which involves discovering an underlying rule to aid completion . 0 ###LEFT-WALL### 5 consolidation 0 ###LEFT-WALL### 7 assessed 0 ###LEFT-WALL### 23 , 0 ###LEFT-WALL### 33 . 1 sleep 2 - 1 sleep 5 consolidation 3 dependent 4 memory 4 memory 5 consolidation 5 consolidation 6 was 6 was 7 assessed 7 assessed 8 using 8 using 16 and 9 a 15 task 10 novel 12 - 10 novel 13 word 13 word 15 task 14 learning 15 task 15 task 16 and 16 and 22 puzzle 16 and 23 , 17 the 22 puzzle 18 tower 19 of 18 tower 22 puzzle 19 of 20 hanoi 21 cognitive 22 puzzle 23 , 24 which 23 , 25 involves 24 which 25 involves 25 involves 26 discovering 26 discovering 29 rule 26 discovering 30 to 27 an 29 rule 28 underlying 29 rule 30 to 32 completion 31 aid 32 completion children were trained on the two tasks and retested following approximately equal retention intervals of both wake and sleep . 0 ###LEFT-WALL### 1 children 0 ###LEFT-WALL### 3 trained 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 20 . 1 children 2 were 2 were 3 trained 3 trained 4 on 4 on 7 tasks 5 the 6 two 6 two 7 tasks 8 and 14 intervals 8 and 18 and 9 retested 10 following 10 following 14 intervals 11 approximately 12 equal 12 equal 13 retention 13 retention 14 intervals 14 intervals 15 of 14 intervals 18 and 15 of 16 both 17 wake 18 and 18 and 19 sleep after sleep , children showed significant improvements in performance of 14 % on the [non] [-] word learning task and 25 % on the tower of hanoi task , but no significant change in [score] following the wake retention interval . 0 ###LEFT-WALL### 4 children 0 ###LEFT-WALL### 5 showed 1 after 2 sleep 1 after 3 , 1 after 4 children 4 children 5 showed 5 showed 7 improvements 5 showed 8 in 5 showed 22 % 5 showed 28 task 6 significant 7 improvements 8 in 9 performance 9 performance 10 of 10 of 20 and 11 14 12 % 11 14 20 and 12 % 13 on 12 % 19 task 13 on 17 word 14 the 17 word 17 word 18 learning 20 and 21 25 21 25 22 % 22 % 23 on 22 % 28 task 23 on 25 tower 24 the 25 tower 25 tower 26 of 26 of 27 hanoi 28 task 30 but 29 , 30 but 30 but 33 change 30 but 41 . 31 no 33 change 32 significant 33 change 33 change 34 in 34 in 36 following 36 following 40 interval 37 the 40 interval 38 wake 39 retention 39 retention 40 interval improved performance on the tower of hanoi may have been due to children consolidating explicit aspects of the task , for example rule - learning or memory of previous sequences ; thus , we propose that sleep is necessary for consolidation of explicit memory in children . 0 ###LEFT-WALL### 1 improved 0 ###LEFT-WALL### 10 been 0 ###LEFT-WALL### 31 ; 0 ###LEFT-WALL### 47 . 1 improved 10 been 2 performance 3 on 2 performance 6 of 2 performance 8 may 3 on 5 tower 4 the 5 tower 6 of 7 hanoi 8 may 9 have 9 have 10 been 10 been 11 due 11 due 12 to 12 to 26 or 13 children 14 consolidating 13 children 26 or 14 consolidating 16 aspects 15 explicit 16 aspects 16 aspects 17 of 16 aspects 25 learning 17 of 19 task 18 the 19 task 19 task 22 example 20 , 22 example 21 for 22 example 22 example 23 rule 22 example 24 - 26 or 27 memory 26 or 28 of 28 of 30 sequences 29 previous 30 sequences 31 ; 34 we 31 ; 35 propose 32 thus 33 , 32 thus 34 we 34 we 35 propose 35 propose 36 that 36 that 37 sleep 36 that 38 is 37 sleep 38 is 38 is 39 necessary 39 necessary 40 for 39 necessary 45 in 40 for 41 consolidation 41 consolidation 42 of 42 of 44 memory 43 explicit 44 memory 45 in 46 children sleep quality and duration were not related to children 's task performance . 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 5 were 0 ###LEFT-WALL### 13 . 1 sleep 2 quality 2 quality 3 and 3 and 4 duration 3 and 5 were 5 were 6 not 5 were 8 to 6 not 7 related 8 to 12 performance 9 children 10 's 10 's 12 performance 11 task 12 performance if such experimental sleep - related learning enhancement is generalizable to everyday life , then it is clear that sleep plays a vital role in children 's educational attainment . 0 ###LEFT-WALL### 16 it 0 ###LEFT-WALL### 17 is 0 ###LEFT-WALL### 30 . 1 if 4 sleep 1 if 9 is 1 if 14 , 1 if 16 it 2 such 4 sleep 3 experimental 4 sleep 4 sleep 9 is 5 - 6 related 6 related 7 learning 6 related 9 is 7 learning 8 enhancement 9 is 10 generalizable 10 generalizable 11 to 11 to 13 life 12 everyday 13 life 15 then 16 it 16 it 17 is 17 is 18 clear 18 clear 19 that 19 that 20 sleep 19 that 21 plays 20 sleep 21 plays 21 plays 24 role 21 plays 25 in 22 a 23 vital 22 a 24 role 23 vital 24 role 25 in 29 attainment 26 children 27 's 27 's 29 attainment 28 educational 29 attainment none none none what is known and objective : despite intriguing initial and associational studies , there remains little research on opiate - related arterial dysfunction and no longitudinal studies . 0 ###LEFT-WALL### 1 none 0 ###LEFT-WALL### 18 remains 0 ###LEFT-WALL### 24 related 1 none 8 objective 1 none 9 : 1 none 18 remains 2 none 3 none 3 none 4 what 4 what 5 is 5 is 6 known 6 known 7 and 7 and 8 objective 8 objective 9 : 9 : 10 despite 9 : 17 there 10 despite 11 intriguing 11 intriguing 13 and 12 initial 13 and 13 and 15 studies 13 and 16 , 14 associational 15 studies 18 remains 20 research 18 remains 21 on 19 little 20 research 21 on 22 opiate 23 - 24 related 24 related 27 and 24 related 31 . 25 arterial 26 dysfunction 26 dysfunction 27 and 27 and 30 studies 28 no 30 studies 29 longitudinal 30 studies as opiates act potently via p16ink4a/cdkn2a identified on gwas screens , and as arterial ageing is a surrogate for organismal ageing , this area is of general concern . 0 ###LEFT-WALL### 3 act 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 29 . 1 as 2 opiates 1 as 3 act 3 act 4 potently 3 act 5 via 5 via 6 p16ink4a/cdkn2a 6 p16ink4a/cdkn2a 7 identified 7 identified 8 on 8 on 10 screens 9 gwas 10 screens 11 , 12 and 12 and 24 area 12 and 25 is 13 as 15 ageing 13 as 16 is 13 as 22 , 13 as 24 area 14 arterial 15 ageing 15 ageing 16 is 16 is 18 surrogate 17 a 18 surrogate 18 surrogate 19 for 19 for 21 ageing 20 organismal 21 ageing 23 this 24 area 24 area 25 is 25 is 26 of 26 of 28 concern 27 general 28 concern methods : thirty - eight male controls compared with 198 opiate - dependent male patients were studied longitudinally using sphygmocor pulse wave analysis . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 12 - 0 ###LEFT-WALL### 24 . 1 methods 2 : 2 : 7 controls 2 : 9 with 3 thirty 4 - 4 - 5 eight 4 - 7 controls 6 male 7 controls 7 controls 8 compared 9 with 11 opiate 10 198 11 opiate 12 - 15 patients 12 - 17 studied 13 dependent 14 male 14 male 15 patients 15 patients 16 were 16 were 17 studied 17 studied 18 longitudinally 17 studied 19 using 19 using 23 analysis 20 sphygmocor 23 analysis 21 pulse 22 wave 22 wave 23 analysis results and discussion : healthy male controls and opiate - dependent male patients were studied on 125 and 625 occasions , respectively . 0 ###LEFT-WALL### 3 discussion 0 ###LEFT-WALL### 4 : 1 results 2 and 2 and 3 discussion 4 : 8 and 4 : 10 - 5 healthy 7 controls 6 male 7 controls 7 controls 8 and 8 and 9 opiate 10 - 13 patients 10 - 15 studied 11 dependent 13 patients 12 male 13 patients 13 patients 14 were 14 were 15 studied 15 studied 16 on 15 studied 22 respectively 16 on 20 occasions 17 125 18 and 18 and 19 625 18 and 20 occasions 21 , 22 respectively 22 respectively 23 . the mean ( ±sem ) chronological age ( ca ) was 42·32 ± 2·22 for controls and 35·04 ± 0·61 for opiate dependent [(] p = 0·0029 [ )( 0 ###LEFT-WALL### 7 age 0 ###LEFT-WALL### 11 was 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 29 )( 1 the 7 age 2 mean 4 ±sem 2 mean 7 age 3 ( 4 ±sem 4 ±sem 5 ) 6 chronological 7 age 7 age 9 ca 7 age 11 was 8 ( 9 ca 9 ca 10 ) 11 was 14 2·22 12 42·32 14 2·22 13 ± 14 2·22 14 2·22 15 for 15 for 16 controls 17 and 19 ± 17 and 26 = 18 35·04 19 ± 19 ± 20 0·61 19 ± 26 = 20 0·61 21 for 21 for 23 dependent 22 opiate 23 dependent 23 dependent 25 p 26 = 27 0·0029 controlling for bmi and ca , there was a significant time : addictive status interaction for vascular age ( p = 0·0127 [ )(and central augmentation pressure and index ( both [p] [<] 0·02 ) . 0 ###LEFT-WALL### 1 controlling 0 ###LEFT-WALL### 12 : 0 ###LEFT-WALL### 36 . 1 controlling 2 for 1 controlling 7 there 1 controlling 8 was 2 for 4 and 3 bmi 4 and 4 and 5 ca 4 and 6 , 8 was 11 time 9 a 11 time 10 significant 11 time 12 : 28 and 13 addictive 14 status 14 status 15 interaction 15 interaction 16 for 15 interaction 24 )(and 16 for 18 age 17 vascular 18 age 18 age 21 = 19 ( 21 = 20 p 21 = 21 = 22 0·0127 24 )(and 27 pressure 24 )(and 28 and 25 central 26 augmentation 26 augmentation 27 pressure 28 and 29 index 28 and 34 0·02 30 ( 34 0·02 31 both 34 0·02 34 0·02 35 ) central systolic and diastolic pressures were also worse over time by addictive status ( p < 0·005 [ )( 0 ###LEFT-WALL### 5 pressures 0 ###LEFT-WALL### 6 were 0 ###LEFT-WALL### 19 )( 1 central 5 pressures 2 systolic 3 and 3 and 4 diastolic 3 and 5 pressures 5 pressures 6 were 6 were 7 also 6 were 8 worse 8 worse 9 over 8 worse 11 by 9 over 10 time 11 by 13 status 12 addictive 13 status 13 status 16 < 14 ( 16 < 15 p 16 < 16 < 17 0·005 at repeated measures multiple regression adjusted for classical risk factors , opiate dose and duration of opiate use remained significant . 0 ###LEFT-WALL### 5 regression 0 ###LEFT-WALL### 19 remained 0 ###LEFT-WALL### 21 . 1 at 3 measures 1 at 5 regression 2 repeated 3 measures 4 multiple 5 regression 5 regression 6 adjusted 5 regression 16 of 5 regression 19 remained 6 adjusted 7 for 7 for 14 and 8 classical 10 factors 9 risk 10 factors 10 factors 11 , 11 , 13 dose 11 , 14 and 12 opiate 13 dose 14 and 15 duration 16 of 18 use 17 opiate 18 use 19 remained 20 significant the dose - duration effect was significant in 8 terms and by time . 0 ###LEFT-WALL### 2 dose 0 ###LEFT-WALL### 3 - 1 the 2 dose 3 - 5 effect 3 - 6 was 3 - 14 . 4 duration 5 effect 5 effect 6 was 6 was 7 significant 7 significant 11 and 8 in 10 terms 8 in 11 and 9 8 10 terms 11 and 12 by 12 by 13 time a similar model quadratic in opiate duration was more powerfully predictive , suggesting the salience of the duration of opiate treatment ( aic 191·6898 and 191·5966 , p = 0·0116 ) . 0 ###LEFT-WALL### 3 model 0 ###LEFT-WALL### 8 was 0 ###LEFT-WALL### 32 . 1 a 2 similar 1 a 3 model 2 similar 3 model 3 model 4 quadratic 3 model 8 was 4 quadratic 5 in 5 in 7 duration 6 opiate 7 duration 8 was 10 powerfully 8 was 11 predictive 9 more 10 powerfully 11 predictive 13 suggesting 12 , 13 suggesting 13 suggesting 15 salience 13 suggesting 31 ) 14 the 15 salience 15 salience 16 of 15 salience 19 of 16 of 18 duration 17 the 18 duration 19 of 21 treatment 20 opiate 21 treatment 21 treatment 25 and 22 ( 25 and 23 aic 24 191·6898 24 191·6898 25 and 25 and 26 191·5966 25 and 29 = 25 and 31 ) 27 , 29 = 28 p 29 = 29 = 30 0·0116 what is new and conclusion : data suggest that increased length of opiate dependence is associated with advanced vascular stiffness and ageing [and] are therefore consistent with accelerated ageing organismally . 0 ###LEFT-WALL### 5 conclusion 0 ###LEFT-WALL### 6 : 0 ###LEFT-WALL### 31 . 1 what 2 is 2 is 3 new 3 new 4 and 4 and 5 conclusion 6 : 7 data 6 : 8 suggest 7 data 8 suggest 8 suggest 9 that 9 that 21 and 9 that 24 are 10 increased 11 length 11 length 12 of 11 length 16 associated 11 length 21 and 12 of 13 opiate 13 opiate 14 dependence 13 opiate 15 is 14 dependence 15 is 16 associated 17 with 17 with 20 stiffness 18 advanced 20 stiffness 19 vascular 20 stiffness 21 and 22 ageing 21 and 24 are 24 are 25 therefore 24 are 26 consistent 26 consistent 27 with 26 consistent 30 organismally 27 with 29 ageing 28 accelerated 29 ageing the superiority of power functions of the opiate duration of exposure underscores the significance of the duration of treatment and [of] putative senescence induction . 0 ###LEFT-WALL### 2 superiority 0 ###LEFT-WALL### 12 underscores 0 ###LEFT-WALL### 25 . 1 the 2 superiority 2 superiority 3 of 2 superiority 6 of 2 superiority 12 underscores 3 of 5 functions 4 power 5 functions 6 of 9 duration 7 the 9 duration 8 opiate 9 duration 9 duration 10 of 10 of 11 exposure 12 underscores 14 significance 13 the 14 significance 14 significance 15 of 15 of 17 duration 16 the 17 duration 17 duration 18 of 18 of 20 and 19 treatment 20 and 20 and 24 induction 22 putative 23 senescence 23 senescence 24 induction an endless number of career trajectories are possible for gerontologists . 0 ###LEFT-WALL### 6 trajectories 0 ###LEFT-WALL### 7 are 0 ###LEFT-WALL### 11 . 1 an 2 endless 1 an 3 number 2 endless 3 number 3 number 4 of 3 number 6 trajectories 4 of 6 trajectories 5 career 6 trajectories 6 trajectories 7 are 7 are 8 possible 8 possible 9 for 9 for 10 gerontologists with a growing aging population , our skills and areas of expertise are of high value to numerous industries . 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 13 are 0 ###LEFT-WALL### 20 . 1 with 5 population 1 with 6 , 1 with 9 and 2 a 5 population 3 growing 5 population 4 aging 5 population 7 our 8 skills 8 skills 9 and 9 and 10 areas 9 and 11 of 9 and 13 are 11 of 12 expertise 13 are 14 of 13 are 17 to 14 of 16 value 15 high 16 value 17 to 19 industries 18 numerous 19 industries the purpose of this study is to describe the professional development and career trajectories of alumni [of] u.s . doctoral gerontology programs obtained through the gerontology education longitudinal study ( gels ) . 0 ###LEFT-WALL### 2 purpose 0 ###LEFT-WALL### 19 . 1 the 2 purpose 2 purpose 3 of 2 purpose 6 is 3 of 5 study 4 this 5 study 6 is 7 to 6 is 12 and 7 to 12 and 8 describe 11 development 8 describe 12 and 9 the 11 development 10 professional 11 development 12 and 13 career 12 and 14 trajectories 14 trajectories 15 of 15 of 18 u.s 16 alumni 18 u.s 19 . 22 programs 19 . 23 obtained 19 . 33 . 20 doctoral 21 gerontology 21 gerontology 22 programs 22 programs 23 obtained 23 obtained 24 through 23 obtained 29 study 24 through 26 gerontology 25 the 26 gerontology 27 education 28 longitudinal 28 longitudinal 29 study 29 study 31 gels 30 ( 31 gels 31 gels 32 ) specifically , the authors examine how professional identification , doctoral program career preparation , and perception of job prospects affect alumni decisions to pursue " traditional " ( i.e [.] , academic ) [versus] ["] nontraditional " ( i.e [.] , [non] - academic ) careers . 0 ###LEFT-WALL### 4 authors 0 ###LEFT-WALL### 5 examine 0 ###LEFT-WALL### 31 , 0 ###LEFT-WALL### 47 . 1 specifically 2 , 1 specifically 4 authors 3 the 4 authors 4 authors 5 examine 5 examine 6 how 6 how 15 and 6 how 20 affect 7 professional 8 identification 8 identification 9 , 9 , 13 preparation 9 , 15 and 10 doctoral 11 program 11 program 13 preparation 12 career 13 preparation 14 , 15 and 15 and 16 perception 15 and 17 of 15 and 20 affect 17 of 19 prospects 18 job 19 prospects 20 affect 22 decisions 21 alumni 22 decisions 22 decisions 23 to 22 decisions 24 pursue 22 decisions 26 traditional 22 decisions 29 i.e 23 to 24 pursue 24 pursue 25 " 26 traditional 27 " 28 ( 29 i.e 29 i.e 31 , 31 , 46 careers 32 academic 33 ) 32 academic 46 careers 36 nontraditional 37 " 36 nontraditional 39 i.e 36 nontraditional 43 - 36 nontraditional 46 careers 38 ( 39 i.e 39 i.e 41 , 44 academic 45 ) 44 academic 46 careers results from the gels revealed a fairly even split in the alumni sample of careers in traditional and nontraditional settings . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 5 revealed 0 ###LEFT-WALL### 21 . 1 results 2 from 1 results 5 revealed 2 from 4 gels 3 the 4 gels 5 revealed 9 split 5 revealed 10 in 5 revealed 16 in 6 a 9 split 7 fairly 8 even 8 even 9 split 10 in 13 sample 11 the 13 sample 12 alumni 13 sample 13 sample 14 of 14 of 15 careers 16 in 20 settings 17 traditional 18 and 18 and 19 nontraditional 18 and 20 settings the decision to pursue a traditional [versus] nontraditional career was not significantly associated with personal identification , doctoral program career preparation , or perception of employment options . 0 ###LEFT-WALL### 2 decision 0 ###LEFT-WALL### 13 associated 0 ###LEFT-WALL### 28 . 1 the 2 decision 2 decision 3 to 2 decision 4 pursue 2 decision 10 was 3 to 4 pursue 4 pursue 9 career 5 a 6 traditional 5 a 9 career 6 traditional 9 career 8 nontraditional 9 career 10 was 11 not 10 was 13 associated 12 significantly 13 associated 13 associated 14 with 14 with 23 or 15 personal 16 identification 16 identification 17 , 17 , 21 preparation 17 , 23 or 18 doctoral 21 preparation 19 program 21 preparation 20 career 21 preparation 22 , 23 or 23 or 24 perception 23 or 25 of 25 of 27 options 26 employment 27 options these results suggest that the skill set obtained in doctoral gerontology programs is useful and is in demand in a variety of careers ; therefore , doctoral programs may want to consider tailoring training to meet students ' future career goals in both academic [and] [non] - academic settings . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 15 and 0 ###LEFT-WALL### 24 ; 0 ###LEFT-WALL### 30 want 0 ###LEFT-WALL### 50 . 1 these 2 results 2 results 3 suggest 3 suggest 4 that 4 that 6 skill 4 that 15 and 5 the 6 skill 6 skill 7 set 6 skill 8 obtained 8 obtained 9 in 9 in 12 programs 10 doctoral 12 programs 11 gerontology 12 programs 13 is 14 useful 13 is 15 and 15 and 16 is 15 and 19 in 16 is 17 in 17 in 18 demand 19 in 21 variety 20 a 21 variety 21 variety 22 of 22 of 23 careers 24 ; 28 programs 25 therefore 26 , 25 therefore 28 programs 27 doctoral 28 programs 28 programs 29 may 29 may 30 want 30 want 31 to 30 want 35 to 30 want 42 in 31 to 32 consider 32 consider 33 tailoring 33 tailoring 34 training 35 to 41 goals 36 meet 37 students 37 students 38 ' 38 ' 41 goals 39 future 41 goals 40 career 41 goals 42 in 49 settings 43 both 49 settings 44 academic 47 - 44 academic 49 settings 48 academic 49 settings there have been few replications of efficacious evidence - based programs for dementia caregivers offered in community settings . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 3 been 1 there 2 have 2 have 3 been 3 been 5 replications 4 few 5 replications 5 replications 6 of 6 of 8 evidence 7 efficacious 8 evidence 8 evidence 11 programs 9 - 11 programs 10 based 11 programs 11 programs 12 for 11 programs 15 offered 11 programs 19 . 12 for 14 caregivers 13 dementia 14 caregivers 15 offered 16 in 16 in 18 settings 17 community 18 settings this study highlights the replication of the evidence - based reducing disability in alzheimer 's disease program and explores the changes in outcomes for participating caregivers and whether those changes are related to level of program utilization . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 highlights 0 ###LEFT-WALL### 9 - 0 ###LEFT-WALL### 36 program 0 ###LEFT-WALL### 38 . 1 this 2 study 2 study 3 highlights 3 highlights 5 replication 4 the 5 replication 5 replication 6 of 6 of 8 evidence 7 the 8 evidence 9 - 18 and 10 based 12 disability 10 based 13 in 10 based 18 and 11 reducing 12 disability 13 in 17 program 14 alzheimer 15 's 15 's 17 program 16 disease 17 program 18 and 19 explores 19 explores 21 changes 19 explores 22 in 19 explores 24 for 20 the 21 changes 22 in 23 outcomes 24 for 27 and 25 participating 26 caregivers 26 caregivers 27 and 27 and 28 whether 27 and 30 changes 27 and 35 of 27 and 36 program 29 those 30 changes 30 changes 31 are 31 are 32 related 32 related 33 to 33 to 34 level 34 level 35 of 36 program 37 utilization with data from 219 caregivers , regression results indicate that more exercise sessions are associated with a decrease in caregiver strain and more behavior management sessions are associated with a decrease in unmet needs after 3 months . 0 ###LEFT-WALL### 21 strain 0 ###LEFT-WALL### 22 and 0 ###LEFT-WALL### 38 . 1 with 2 data 1 with 16 with 1 with 21 strain 2 data 3 from 2 data 15 associated 3 from 5 caregivers 4 219 5 caregivers 6 , 15 associated 7 regression 8 results 8 results 9 indicate 9 indicate 10 that 10 that 13 sessions 10 that 15 associated 11 more 13 sessions 12 exercise 13 sessions 13 sessions 14 are 14 are 15 associated 16 with 18 decrease 17 a 18 decrease 18 decrease 19 in 19 in 20 caregiver 22 and 26 sessions 22 and 28 associated 23 more 26 sessions 24 behavior 26 sessions 25 management 26 sessions 26 sessions 27 are 27 are 28 associated 28 associated 29 with 28 associated 35 after 29 with 31 decrease 29 with 32 in 30 a 31 decrease 32 in 34 needs 33 unmet 34 needs 35 after 37 months 36 3 37 months findings demonstrate how a multicomponent program can have positive benefits for family caregivers . 0 ###LEFT-WALL### 1 findings 0 ###LEFT-WALL### 2 demonstrate 0 ###LEFT-WALL### 14 . 1 findings 2 demonstrate 2 demonstrate 3 how 3 how 6 program 3 how 8 have 4 a 5 multicomponent 4 a 6 program 5 multicomponent 6 program 6 program 7 can 7 can 8 have 8 have 10 benefits 9 positive 10 benefits 10 benefits 11 for 11 for 13 caregivers 12 family 13 caregivers given the rise in the aging population and the increased use of health care services , there is a demand for awareness and training that targets underserved populations such as older lesbian [,] gay , bisexual , and transgender ( lgbt ) adults . 0 ###LEFT-WALL### 17 there 0 ###LEFT-WALL### 26 targets 0 ###LEFT-WALL### 44 . 1 given 3 rise 1 given 16 , 1 given 17 there 2 the 3 rise 3 rise 4 in 4 in 8 and 5 the 7 population 6 aging 7 population 7 population 8 and 8 and 11 use 8 and 12 of 8 and 14 care 8 and 15 services 9 the 11 use 10 increased 11 use 12 of 13 health 14 care 15 services 17 there 18 is 18 is 20 demand 19 a 20 demand 20 demand 21 for 21 for 23 and 22 awareness 23 and 23 and 24 training 23 and 25 that 23 and 26 targets 25 that 26 targets 26 targets 28 populations 26 targets 30 as 27 underserved 28 populations 29 such 30 as 30 as 43 adults 31 older 32 lesbian 32 lesbian 43 adults 34 gay 38 and 34 gay 42 ) 34 gay 43 adults 35 , 38 and 36 bisexual 38 and 37 , 38 and 38 and 39 transgender 38 and 41 lgbt 38 and 42 ) 40 ( 41 lgbt 41 lgbt 42 ) older lgbt adults are 5 times less likely to access health care and social services ( king , 2009 ) . 0 ###LEFT-WALL### 3 adults 0 ###LEFT-WALL### 4 are 0 ###LEFT-WALL### 21 . 1 older 3 adults 2 lgbt 3 adults 3 adults 4 are 4 are 8 likely 5 5 6 times 6 times 7 less 7 less 8 likely 8 likely 9 to 8 likely 10 access 9 to 10 access 10 access 13 and 11 health 12 care 12 care 13 and 13 and 15 services 13 and 17 king 13 and 19 2009 14 social 15 services 16 ( 17 king 17 king 18 , 18 , 19 2009 19 2009 20 ) ethically responsible health service delivery is needed to capitalize on the strengths and capabilities of older lgbt adults and is vital for combating existing health disparities . 0 ###LEFT-WALL### 5 delivery 0 ###LEFT-WALL### 19 and 0 ###LEFT-WALL### 27 . 1 ethically 5 delivery 2 responsible 3 health 3 health 5 delivery 4 service 5 delivery 5 delivery 19 and 6 is 7 needed 6 is 19 and 7 needed 8 to 7 needed 10 on 8 to 9 capitalize 10 on 13 and 11 the 12 strengths 12 strengths 13 and 13 and 14 capabilities 13 and 15 of 15 of 18 adults 16 older 18 adults 17 lgbt 18 adults 19 and 20 is 19 and 26 disparities 20 is 21 vital 21 vital 22 for 22 for 23 combating 23 combating 25 health 24 existing 25 health social workers aim to prevent ongoing gaps in care for older lgbt adults that can lead to negative individual and social consequences . 0 ###LEFT-WALL### 2 workers 0 ###LEFT-WALL### 3 aim 0 ###LEFT-WALL### 23 . 1 social 2 workers 2 workers 3 aim 3 aim 4 to 3 aim 8 in 3 aim 13 adults 3 aim 17 to 4 to 5 prevent 5 prevent 7 gaps 6 ongoing 7 gaps 8 in 9 care 9 care 10 for 10 for 12 lgbt 11 older 12 lgbt 13 adults 14 that 13 adults 15 can 14 that 15 can 15 can 16 lead 17 to 18 negative 18 negative 22 consequences 19 individual 20 and 20 and 21 social 20 and 22 consequences this study describes the previously unexplored subsample of respondents who reported at least 1 [same] [-] sex sexual relationship ( sssr ) in the national social life , health , and aging project ( nshap ) . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 describes 0 ###LEFT-WALL### 37 . 1 this 2 study 2 study 3 describes 3 describes 7 subsample 4 the 7 subsample 5 previously 6 unexplored 6 unexplored 7 subsample 7 subsample 8 of 7 subsample 10 who 7 subsample 11 reported 8 of 9 respondents 10 who 11 reported 11 reported 19 relationship 11 reported 23 in 12 at 13 least 13 least 14 1 14 1 19 relationship 17 sex 19 relationship 18 sexual 19 relationship 19 relationship 21 sssr 20 ( 21 sssr 21 sssr 22 ) 23 in 31 and 24 the 27 life 25 national 26 social 26 social 27 life 27 life 28 , 28 , 29 health 28 , 31 and 30 , 31 and 31 and 35 nshap 32 aging 33 project 33 project 35 nshap 34 ( 35 nshap 35 nshap 36 ) the nshap collected data from 3,005 adults ( aged 57 - 85 ) . 0 ###LEFT-WALL### 2 nshap 0 ###LEFT-WALL### 3 collected 0 ###LEFT-WALL### 14 . 1 the 2 nshap 2 nshap 3 collected 3 collected 4 data 4 data 5 from 5 from 7 adults 6 3,005 7 adults 7 adults 9 aged 8 ( 9 aged 9 aged 11 - 9 aged 13 ) 10 57 11 - 11 - 12 85 approximately 4 % ( n = 102 [ )(of respondents reported at least one sssr . 0 ###LEFT-WALL### 3 % 0 ###LEFT-WALL### 11 reported 0 ###LEFT-WALL### 16 . 1 approximately 2 4 2 4 3 % 3 % 6 = 3 % 11 reported 4 ( 6 = 5 n 6 = 6 = 7 102 7 102 9 )(of 9 )(of 10 respondents 11 reported 15 sssr 12 at 13 least 13 least 14 one 14 one 15 sssr these sexual minority elders were younger , more educated , were more likely to be working , had fewer social supports , and better physical health . 0 ###LEFT-WALL### 4 elders 0 ###LEFT-WALL### 5 were 0 ###LEFT-WALL### 7 , 0 ###LEFT-WALL### 27 . 1 these 4 elders 2 sexual 3 minority 3 minority 4 elders 4 elders 5 were 5 were 6 younger 7 , 8 more 7 , 10 , 8 more 10 , 9 educated 10 , 10 , 11 were 10 , 26 health 12 more 26 health 13 likely 14 to 13 likely 17 , 13 likely 23 and 14 to 17 , 15 be 16 working 15 be 17 , 17 , 18 had 18 had 21 supports 19 fewer 21 supports 20 social 21 supports 22 , 23 and 23 and 24 better 23 and 26 health 25 physical 26 health results may indicate crisis competence in sexual minority elders . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 3 indicate 0 ###LEFT-WALL### 10 . 1 results 2 may 2 may 3 indicate 3 indicate 5 competence 3 indicate 6 in 4 crisis 5 competence 6 in 9 elders 7 sexual 8 minority 8 minority 9 elders collecting sexual orientation and gender identity data in larger , us - based probability samples would inform the development of appropriate community [-] based services and supports . 0 ###LEFT-WALL### 1 collecting 0 ###LEFT-WALL### 13 based 0 ###LEFT-WALL### 28 . 1 collecting 4 and 1 collecting 13 based 2 sexual 3 orientation 3 orientation 4 and 4 and 7 data 4 and 12 - 5 gender 6 identity 6 identity 7 data 7 data 8 in 8 in 11 us 9 larger 10 , 9 larger 11 us 13 based 15 samples 14 probability 15 samples 15 samples 26 and 16 would 17 inform 16 would 26 and 17 inform 19 development 18 the 19 development 19 development 20 of 20 of 25 services 21 appropriate 25 services 22 community 24 based 24 based 25 services 26 and 27 supports cellular senescence is thought to play a major role in age - related diseases , which cause nearly 67 % of all human deaths worldwide . 0 ###LEFT-WALL### 1 cellular 0 ###LEFT-WALL### 4 thought 0 ###LEFT-WALL### 13 related 0 ###LEFT-WALL### 15 , 0 ###LEFT-WALL### 26 . 1 cellular 2 senescence 1 cellular 3 is 1 cellular 4 thought 2 senescence 3 is 4 thought 5 to 4 thought 10 in 5 to 6 play 6 play 9 role 7 a 9 role 8 major 9 role 10 in 11 age 12 - 13 related 13 related 14 diseases 15 , 16 which 15 , 17 cause 16 which 17 cause 17 cause 20 % 17 cause 25 worldwide 18 nearly 19 67 19 67 20 % 20 % 21 of 21 of 24 deaths 22 all 24 deaths 23 human 24 deaths recent research in mice showed that exercising mice had higher levels of telomerase , an enzyme that helps maintain telomere length , than nonexercising mice . 0 ###LEFT-WALL### 2 research 0 ###LEFT-WALL### 5 showed 0 ###LEFT-WALL### 26 . 1 recent 2 research 2 research 3 in 2 research 5 showed 3 in 4 mice 5 showed 6 that 6 that 7 exercising 6 that 9 had 7 exercising 8 mice 7 exercising 9 had 9 had 11 levels 9 had 23 than 10 higher 11 levels 11 levels 12 of 12 of 13 telomerase 13 telomerase 16 enzyme 14 , 16 enzyme 15 an 16 enzyme 16 enzyme 17 that 16 enzyme 18 helps 16 enzyme 22 , 17 that 18 helps 18 helps 19 maintain 19 maintain 21 length 20 telomere 21 length 23 than 25 mice 24 nonexercising 25 mice a commonly used model for biological aging was proposed by penna . 0 ###LEFT-WALL### 4 model 0 ###LEFT-WALL### 9 proposed 0 ###LEFT-WALL### 12 . 1 a 4 model 2 commonly 3 used 3 used 4 model 4 model 5 for 4 model 8 was 5 for 7 aging 6 biological 7 aging 8 was 9 proposed 9 proposed 10 by 10 by 11 penna i propose a modification of the penna model that incorporates cellular senescence and find an analytical steady - state solution following coe , mao , and cates [[] phys . rev [.] lett [.] 89 , 288103 ( 2002 ) ] . 0 ###LEFT-WALL### 1 i 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 30 . 1 i 13 and 2 propose 4 modification 2 propose 13 and 3 a 4 modification 4 modification 5 of 4 modification 9 that 4 modification 10 incorporates 5 of 8 model 6 the 8 model 7 penna 8 model 9 that 10 incorporates 10 incorporates 12 senescence 11 cellular 12 senescence 13 and 14 find 14 find 20 solution 14 find 22 coe 14 find 26 and 15 an 16 analytical 15 an 20 solution 16 analytical 19 state 17 steady 18 - 17 steady 19 state 19 state 20 solution 20 solution 21 following 22 coe 24 mao 23 , 24 mao 24 mao 25 , 25 , 26 and 26 and 29 phys 27 cates 29 phys 30 . 31 rev 30 . 42 . 31 rev 33 lett 33 lett 35 89 33 lett 37 288103 36 , 37 288103 37 288103 39 2002 37 288103 41 ] 38 ( 39 2002 39 2002 40 ) i find that models corresponding to delayed cellular senescence have younger populations that live longer . 0 ###LEFT-WALL### 1 i 0 ###LEFT-WALL### 2 find 0 ###LEFT-WALL### 16 . 1 i 2 find 2 find 3 that 3 that 4 models 3 that 10 have 4 models 5 corresponding 4 models 10 have 5 corresponding 6 to 6 to 9 senescence 7 delayed 9 senescence 8 cellular 9 senescence 10 have 12 populations 11 younger 12 populations 12 populations 13 that 12 populations 14 live 13 that 14 live 14 live 15 longer i fit the model to the united kingdom 's death distribution , which the original penna model cannot do . 0 ###LEFT-WALL### 1 i 0 ###LEFT-WALL### 2 fit 1 i 2 fit 2 fit 4 model 2 fit 5 to 3 the 4 model 5 to 11 distribution 6 the 8 kingdom 7 united 8 kingdom 8 kingdom 9 's 9 's 11 distribution 10 death 11 distribution 11 distribution 13 which 12 , 13 which 13 which 19 do 13 which 20 . 14 the 17 model 15 original 17 model 16 penna 17 model 17 model 18 cannot 18 cannot 19 do correlations among low - frequency spontaneous fluctuations in the blood oxygen level - dependent ( bold ) signal reflect the connectivity of intrinsic large - scale networks in the brain . 0 ###LEFT-WALL### 1 correlations 0 ###LEFT-WALL### 19 reflect 0 ###LEFT-WALL### 31 . 1 correlations 2 among 1 correlations 19 reflect 2 among 7 fluctuations 3 low 4 - 3 low 5 frequency 5 frequency 7 fluctuations 6 spontaneous 7 fluctuations 7 fluctuations 8 in 8 in 18 signal 9 the 18 signal 10 blood 18 signal 11 oxygen 18 signal 12 level 13 - 12 level 18 signal 14 dependent 16 bold 14 dependent 18 signal 15 ( 16 bold 16 bold 17 ) 19 reflect 21 connectivity 19 reflect 28 in 20 the 21 connectivity 21 connectivity 22 of 22 of 27 networks 23 intrinsic 26 scale 24 large 25 - 24 large 26 scale 26 scale 27 networks 28 in 30 brain 29 the 30 brain these correlations have typically been characterized over the entire timecourse ( mean connectivity ) , but the mean correlations between regions vary dynamically . 0 ###LEFT-WALL### 2 correlations 0 ###LEFT-WALL### 6 characterized 0 ###LEFT-WALL### 16 but 0 ###LEFT-WALL### 24 . 1 these 2 correlations 2 correlations 3 have 3 have 5 been 4 typically 5 been 5 been 6 characterized 6 characterized 7 over 7 over 10 timecourse 8 the 10 timecourse 9 entire 10 timecourse 10 timecourse 13 connectivity 11 ( 13 connectivity 12 mean 13 connectivity 13 connectivity 14 ) 15 , 16 but 16 but 19 correlations 16 but 22 vary 17 the 19 correlations 18 mean 19 correlations 19 correlations 20 between 19 correlations 22 vary 20 between 21 regions 22 vary 23 dynamically to do this , we [conducted] [a] chained p - technique factor analysis of the correlations in nonoverlapping temporal windows across n=145 normal aging subjects ( age 56 - 89 ) . 0 ###LEFT-WALL### 5 we 0 ###LEFT-WALL### 8 chained 0 ###LEFT-WALL### 10 - 0 ###LEFT-WALL### 32 . 1 to 2 do 1 to 4 , 1 to 5 we 2 do 3 this 5 we 8 chained 8 chained 9 p 10 - 13 analysis 11 technique 13 analysis 12 factor 13 analysis 13 analysis 14 of 13 analysis 27 age 14 of 16 correlations 15 the 16 correlations 16 correlations 17 in 16 correlations 21 across 17 in 20 windows 18 nonoverlapping 20 windows 19 temporal 20 windows 21 across 25 subjects 22 n=145 25 subjects 23 normal 25 subjects 24 aging 25 subjects 26 ( 27 age 27 age 29 - 27 age 31 ) 28 56 29 - 29 - 30 89 the expression of factors within the dmn , fptc , and dan was highly correlated with age : decreased intercorrelations within nodes in each factor were correlated with advanced age . 0 ###LEFT-WALL### 2 expression 0 ###LEFT-WALL### 15 correlated 0 ###LEFT-WALL### 18 : 0 ###LEFT-WALL### 31 . 1 the 2 expression 2 expression 3 of 2 expression 13 was 3 of 4 factors 4 factors 5 within 5 within 11 and 6 the 9 fptc 7 dmn 9 fptc 8 , 9 fptc 9 fptc 10 , 9 fptc 11 and 10 , 11 and 11 and 12 dan 13 was 15 correlated 14 highly 15 correlated 15 correlated 16 with 16 with 17 age 18 : 20 intercorrelations 18 : 27 correlated 19 decreased 20 intercorrelations 20 intercorrelations 21 within 20 intercorrelations 26 were 21 within 22 nodes 22 nodes 23 in 23 in 25 factor 24 each 25 factor 26 were 27 correlated 27 correlated 28 with 28 with 30 age 29 advanced 30 age although these findings converge with those from stationary analysis , the ability to quantify age - related changes in the coherence of fluctuating connectivity may yield more insights into age - related cognitive decline . 0 ###LEFT-WALL### 10 , 0 ###LEFT-WALL### 31 - 1 although 3 findings 1 although 10 , 2 these 3 findings 4 converge 5 with 4 converge 7 from 4 converge 10 , 5 with 6 those 7 from 9 analysis 8 stationary 9 analysis 10 , 26 yield 11 the 12 ability 12 ability 13 to 12 ability 14 quantify 12 ability 25 may 13 to 14 quantify 14 quantify 15 age 16 - 17 related 17 related 18 changes 17 related 19 in 17 related 25 may 19 in 21 coherence 20 the 21 coherence 21 coherence 22 of 22 of 24 connectivity 23 fluctuating 24 connectivity 25 may 26 yield 26 yield 28 insights 26 yield 29 into 27 more 28 insights 29 into 30 age 31 - 34 decline 31 - 35 . 32 related 34 decline 33 cognitive 34 decline occupational and environmental health nurses can improve planning for an aging workforce by reviewing existing programs and services and adding aging and multi - generational workforce issues to ongoing training . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 19 and 0 ###LEFT-WALL### 31 . 1 occupational 2 and 2 and 5 nurses 2 and 6 can 3 environmental 4 health 4 health 5 nurses 6 can 17 and 7 improve 8 planning 7 improve 13 by 7 improve 17 and 8 planning 9 for 9 for 12 workforce 10 an 12 workforce 11 aging 12 workforce 13 by 16 programs 14 reviewing 16 programs 15 existing 16 programs 17 and 18 services 19 and 20 adding 19 and 27 issues 20 adding 22 and 20 adding 27 issues 21 aging 22 and 22 and 26 workforce 23 multi 24 - 23 multi 26 workforce 25 generational 26 workforce 27 issues 28 to 28 to 30 training 29 ongoing 30 training objectives : to inform public health efforts to promote independent functioning among older adults , we have provided new national estimates of late - life disability that explicitly recognize behavioral adaptations . 0 ###LEFT-WALL### 1 objectives 0 ###LEFT-WALL### 2 : 2 : 16 we 2 : 18 provided 2 : 32 . 3 to 4 inform 3 to 15 , 3 to 16 we 4 inform 7 efforts 5 public 6 health 6 health 7 efforts 7 efforts 8 to 7 efforts 9 promote 8 to 9 promote 9 promote 11 functioning 9 promote 12 among 10 independent 11 functioning 12 among 14 adults 13 older 14 adults 16 we 17 have 17 have 18 provided 18 provided 21 estimates 19 new 20 national 20 national 21 estimates 21 estimates 22 of 21 estimates 27 that 21 estimates 29 recognize 22 of 26 disability 23 late 24 - 23 late 26 disability 25 life 26 disability 27 that 29 recognize 28 explicitly 29 recognize 29 recognize 31 adaptations 30 behavioral 31 adaptations methods : we analyzed the 2011 national health and aging trends study , a study of medicare enrollees aged 65 years and older ( n = 8077 ) . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 3 we 2 : 4 analyzed 2 : 13 , 2 : 29 . 3 we 4 analyzed 4 analyzed 12 study 5 the 12 study 6 2011 7 national 7 national 8 health 8 health 9 and 9 and 10 aging 10 aging 11 trends 11 trends 12 study 13 , 15 study 13 , 19 aged 14 a 15 study 15 study 16 of 15 study 19 aged 16 of 18 enrollees 17 medicare 18 enrollees 19 aged 22 and 20 65 21 years 21 years 22 and 22 and 23 older 23 older 26 = 24 ( 26 = 25 n 26 = 26 = 27 8077 26 = 28 ) for 7 mobility and self - care activities we identified 5 hierarchical stages -- fully able , successful accommodation with devices , activity reduction , difficulty [despite] accommodations , and receipt of help -- and explored disparities and associations with quality of life measures . 0 ###LEFT-WALL### 9 we 0 ###LEFT-WALL### 35 and 0 ###LEFT-WALL### 45 . 1 for 8 activities 1 for 9 we 2 7 8 activities 3 mobility 4 and 4 and 5 self 4 and 6 - 4 and 8 activities 7 care 8 activities 9 we 35 and 10 identified 13 stages 10 identified 35 and 11 5 13 stages 12 hierarchical 13 stages 13 stages 19 accommodation 14 -- 19 accommodation 15 fully 16 able 16 able 17 , 16 able 19 accommodation 18 successful 19 accommodation 19 accommodation 20 with 19 accommodation 34 -- 20 with 30 and 21 devices 22 , 22 , 24 reduction 22 , 25 , 23 activity 24 reduction 25 , 28 accommodations 25 , 30 and 26 difficulty 28 accommodations 29 , 30 and 30 and 31 receipt 30 and 32 of 32 of 33 help 35 and 36 explored 35 and 40 with 36 explored 38 and 37 disparities 38 and 38 and 39 associations 40 with 41 quality 41 quality 42 of 42 of 44 measures 43 life 44 measures results : among older adults , 31 % were fully able to complete [self] - care and mobility activities . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 20 . 2 : 8 % 2 : 9 were 3 among 5 adults 3 among 6 , 3 among 8 % 4 older 5 adults 7 31 8 % 8 % 9 were 9 were 11 able 10 fully 11 able 11 able 12 to 12 to 17 and 13 complete 15 - 13 complete 16 care 16 care 17 and 17 and 19 activities 18 mobility 19 activities the remaining groups successfully accommodated with devices ( 25 % ) , [reduced] their activities ( 6 % ) , reported difficulty despite accommodations ( 18 % ) , or received help ( 21 % ) . 0 ###LEFT-WALL### 3 groups 0 ###LEFT-WALL### 30 or 0 ###LEFT-WALL### 37 . 1 the 2 remaining 1 the 3 groups 3 groups 5 accommodated 3 groups 30 or 4 successfully 5 accommodated 5 accommodated 6 with 6 with 7 devices 7 devices 10 % 7 devices 15 activities 8 ( 10 % 9 25 10 % 10 % 11 ) 12 , 15 activities 14 their 15 activities 15 activities 18 % 15 activities 20 , 16 ( 18 % 17 6 18 % 18 % 19 ) 21 reported 22 difficulty 21 reported 23 despite 21 reported 30 or 23 despite 24 accommodations 24 accommodations 27 % 25 ( 27 % 26 18 27 % 27 % 28 ) 29 , 30 or 30 or 31 received 31 received 32 help 32 help 35 % 33 ( 35 % 34 21 35 % 35 % 36 ) with successive stages , physical and cognitive capacity decreased and symptoms and multimorbidity increased . 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 14 increased 0 ###LEFT-WALL### 15 . 1 with 3 stages 1 with 4 , 1 with 12 and 2 successive 3 stages 5 physical 6 and 6 and 7 cognitive 6 and 8 capacity 8 capacity 9 decreased 8 capacity 10 and 10 and 11 symptoms 10 and 12 and 12 and 13 multimorbidity 12 and 14 increased successful accommodation was associated with maintaining participation in valued activities and high well - being , but substantial disparities by race , ethnicity , and income existed . 0 ###LEFT-WALL### 2 accommodation 0 ###LEFT-WALL### 14 - 1 successful 2 accommodation 2 accommodation 3 was 3 was 4 associated 4 associated 5 with 4 associated 8 in 5 with 6 maintaining 6 maintaining 7 participation 8 in 11 and 9 valued 10 activities 10 activities 11 and 11 and 13 well 12 high 13 well 14 - 15 being 14 - 17 but 14 - 28 . 16 , 17 but 17 but 25 and 17 but 27 existed 18 substantial 19 disparities 19 disparities 20 by 19 disparities 25 and 20 by 21 race 21 race 23 ethnicity 22 , 23 ethnicity 23 ethnicity 24 , 25 and 26 income 25 and 27 existed conclusions : increased public health attention to behavioral adaptations to functional change can promote independence for older adults and may enhance quality of life . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 25 . 1 conclusions 2 : 2 : 6 attention 2 : 7 to 2 : 10 to 3 increased 5 health 4 public 5 health 5 health 6 attention 7 to 9 adaptations 8 behavioral 9 adaptations 10 to 12 change 11 functional 12 change 12 change 19 and 12 change 23 of 13 can 14 promote 13 can 19 and 14 promote 15 independence 15 independence 16 for 16 for 18 adults 17 older 18 adults 19 and 20 may 20 may 21 enhance 21 enhance 22 quality 23 of 24 life objectives : we examined the efficiency of country [-] specific health care spending in improving life expectancies for men and women . 0 ###LEFT-WALL### 1 objectives 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 22 . 2 : 3 we 2 : 4 examined 3 we 4 examined 4 examined 6 efficiency 4 examined 14 in 4 examined 18 for 5 the 6 efficiency 6 efficiency 7 of 7 of 13 spending 8 country 13 spending 10 specific 12 care 11 health 12 care 12 care 13 spending 14 in 15 improving 15 improving 17 expectancies 16 life 17 expectancies 18 for 20 and 19 men 20 and 20 and 21 women methods : we estimated efficiencies of health care spending for 27 organisation for economic co - operation and development ( oecd ) [countries] during the period 1991 to 2007 using multivariable regression models , including country fixed - effects and controlling for time - varying levels of national social expenditures , economic development , and health behaviors . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 4 estimated 2 : 3 we 3 we 4 estimated 4 estimated 5 efficiencies 4 estimated 10 for 5 efficiencies 6 of 6 of 9 spending 7 health 8 care 8 care 9 spending 10 for 12 organisation 11 27 12 organisation 12 organisation 13 for 12 organisation 24 during 13 for 15 co 14 economic 15 co 15 co 18 and 16 - 18 and 17 operation 18 and 18 and 21 oecd 18 and 22 ) 19 development 21 oecd 20 ( 21 oecd 21 oecd 22 ) 24 during 30 using 25 the 30 using 26 period 28 to 26 period 30 using 27 1991 28 to 28 to 29 2007 30 using 32 regression 30 using 33 models 30 using 38 - 31 multivariable 32 regression 32 regression 33 models 34 , 38 - 35 including 36 country 36 country 37 fixed 36 country 38 - 38 - 40 and 39 effects 40 and 40 and 41 controlling 40 and 42 for 40 and 46 levels 42 for 43 time 44 - 46 levels 45 varying 46 levels 46 levels 47 of 46 levels 55 and 46 levels 58 . 47 of 50 expenditures 48 national 50 expenditures 49 social 50 expenditures 51 , 55 and 52 economic 53 development 53 development 55 and 54 , 55 and 55 and 57 behaviors 55 and 58 . 56 health 57 behaviors results : findings indicated robust differences in health - spending efficiency . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 3 findings 2 : 4 indicated 3 findings 4 indicated 4 indicated 6 differences 4 indicated 7 in 5 robust 6 differences 7 in 8 health 8 health 10 spending 9 - 10 spending 10 spending 11 efficiency 10 spending 12 . health - spending increases were associated with greater life expectancy improvements for men than for women in nearly every oecd country . 0 ###LEFT-WALL### 4 increases 0 ###LEFT-WALL### 6 associated 0 ###LEFT-WALL### 22 . 1 health 2 - 1 health 4 increases 3 spending 4 increases 4 increases 5 were 5 were 6 associated 6 associated 7 with 6 associated 14 than 7 with 11 improvements 7 with 12 for 8 greater 9 life 9 life 11 improvements 10 expectancy 11 improvements 12 for 13 men 14 than 15 for 15 for 16 women 16 women 17 in 17 in 21 country 18 nearly 19 every 19 every 21 country 20 oecd 21 country conclusions : this is the first study to our knowledge to estimate the effect of country [-] specific health expenditures on life expectancies of men and women . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 3 this 2 : 4 is 2 : 28 . 3 this 4 is 4 is 7 study 5 the 6 first 5 the 7 study 7 study 8 to 7 study 11 to 7 study 12 estimate 8 to 10 knowledge 9 our 10 knowledge 11 to 12 estimate 12 estimate 14 effect 12 estimate 21 on 13 the 14 effect 14 effect 15 of 15 of 20 expenditures 16 country 20 expenditures 18 specific 19 health 19 health 20 expenditures 21 on 23 expectancies 22 life 23 expectancies 23 expectancies 24 of 24 of 26 and 25 men 26 and 26 and 27 women future work understanding the determinants of these differences has the potential to improve the overall efficiency and equity of national health systems . 0 ###LEFT-WALL### 2 work 0 ###LEFT-WALL### 9 has 0 ###LEFT-WALL### 23 . 1 future 2 work 2 work 3 understanding 2 work 6 of 2 work 9 has 3 understanding 5 determinants 4 the 5 determinants 6 of 8 differences 7 these 8 differences 9 has 11 potential 9 has 12 to 10 the 11 potential 12 to 13 improve 13 improve 17 and 14 the 16 efficiency 15 overall 16 efficiency 16 efficiency 17 and 17 and 18 equity 17 and 19 of 19 of 22 systems 20 national 21 health 21 health 22 systems none proximal humerus fractures account for approximately 5 % of all fractures . 0 ###LEFT-WALL### 1 none 0 ###LEFT-WALL### 5 account 0 ###LEFT-WALL### 13 . 1 none 3 humerus 1 none 4 fractures 1 none 5 account 2 proximal 3 humerus 3 humerus 4 fractures 5 account 6 for 6 for 9 % 7 approximately 8 5 8 5 9 % 9 % 10 of 10 of 12 fractures 11 all 12 fractures it is estimated that due to our aging population , orthopaedic surgeons will see a three [-] fold increase in proximal humerus fractures over the next 30 years . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 3 estimated 0 ###LEFT-WALL### 29 . 1 it 2 is 2 is 3 estimated 3 estimated 4 that 4 that 12 surgeons 4 that 14 see 5 due 6 to 6 to 9 population 6 to 10 , 6 to 12 surgeons 7 our 9 population 8 aging 9 population 11 orthopaedic 12 surgeons 12 surgeons 13 will 13 will 14 see 14 see 19 increase 14 see 24 over 15 a 19 increase 16 three 18 fold 18 fold 19 increase 19 increase 20 in 20 in 23 fractures 21 proximal 22 humerus 22 humerus 23 fractures 24 over 28 years 25 the 26 next 25 the 27 30 27 30 28 years internal fixation with locked plating is the current mainstay of treatment for functionally active patients who desire minimal loss [of] [function] . 0 ###LEFT-WALL### 2 fixation 0 ###LEFT-WALL### 6 is 0 ###LEFT-WALL### 22 . 1 internal 2 fixation 2 fixation 3 with 2 fixation 6 is 3 with 5 plating 4 locked 5 plating 6 is 9 mainstay 7 the 9 mainstay 8 current 9 mainstay 9 mainstay 10 of 10 of 11 treatment 11 treatment 12 for 12 for 15 patients 13 functionally 14 active 14 active 15 patients 15 patients 16 who 15 patients 17 desire 16 who 17 desire 17 desire 19 loss 18 minimal 19 loss a thorough understanding of the indications , techniques , and drawbacks of treatment with internal fixation is essential to achieve the highest quality of patient care . 0 ###LEFT-WALL### 3 understanding 0 ###LEFT-WALL### 17 is 0 ###LEFT-WALL### 27 . 1 a 2 thorough 1 a 3 understanding 2 thorough 3 understanding 3 understanding 4 of 3 understanding 17 is 4 of 10 and 5 the 6 indications 6 indications 7 , 7 , 8 techniques 7 , 10 and 9 , 10 and 10 and 11 drawbacks 10 and 12 of 12 of 13 treatment 13 treatment 14 with 14 with 16 fixation 15 internal 16 fixation 17 is 18 essential 18 essential 19 to 18 essential 20 achieve 19 to 20 achieve 20 achieve 23 quality 21 the 22 highest 21 the 23 quality 23 quality 24 of 24 of 26 care 25 patient 26 care through the author 's experiences as a gerontological social worker , graduate student [in] gerontology , and gerontology professor , the author discovered not only the cloud of old age , but three silver linings . 0 ###LEFT-WALL### 22 author 0 ###LEFT-WALL### 23 discovered 0 ###LEFT-WALL### 36 . 1 through 5 experiences 1 through 22 author 2 the 3 author 3 author 4 's 4 's 5 experiences 5 experiences 6 as 5 experiences 17 and 6 as 10 worker 7 a 10 worker 8 gerontological 10 worker 9 social 10 worker 11 , 17 and 12 graduate 15 gerontology 13 student 15 gerontology 15 gerontology 17 and 16 , 17 and 17 and 19 professor 17 and 20 , 18 gerontology 19 professor 21 the 22 author 22 author 23 discovered 23 discovered 32 but 24 not 25 only 25 only 32 but 26 the 27 cloud 27 cloud 28 of 27 cloud 30 age 28 of 30 age 29 old 30 age 30 age 32 but 31 , 32 but 32 but 35 linings 33 three 35 linings 34 silver 35 linings immune profiling [of] [non] - obese diabetic [(] nod ) is a widely employed tool to assess the mechanisms of inflammatory insulitis . 0 ###LEFT-WALL### 2 profiling 0 ###LEFT-WALL### 11 is 0 ###LEFT-WALL### 23 . 1 immune 2 profiling 2 profiling 9 nod 2 profiling 11 is 5 - 9 nod 6 obese 7 diabetic 7 diabetic 9 nod 9 nod 10 ) 11 is 15 tool 12 a 15 tool 13 widely 14 employed 14 employed 15 tool 15 tool 16 to 15 tool 17 assess 16 to 17 assess 17 assess 19 mechanisms 18 the 19 mechanisms 19 mechanisms 20 of 20 of 22 insulitis 21 inflammatory 22 insulitis our analysis of the female nod colony revealed similar distribution of lymphoid lineages to wild type mice , and at various ages of prediabetic and diabetic mice . 0 ###LEFT-WALL### 2 analysis 0 ###LEFT-WALL### 8 revealed 0 ###LEFT-WALL### 28 . 1 our 2 analysis 2 analysis 3 of 2 analysis 8 revealed 3 of 7 colony 4 the 7 colony 5 female 7 colony 6 nod 7 colony 8 revealed 10 distribution 8 revealed 19 and 9 similar 10 distribution 10 distribution 11 of 11 of 13 lineages 12 lymphoid 13 lineages 14 to 17 mice 14 to 19 and 15 wild 16 type 16 type 17 mice 18 , 19 and 19 and 20 at 20 at 22 ages 21 various 22 ages 22 ages 23 of 23 of 27 mice 24 prediabetic 25 and 25 and 26 diabetic 25 and 27 mice the profiles of mesenteric and pancreatic lymph nodes differ and often change reciprocally due to directed migration of t cells towards the site of inflammation . 0 ###LEFT-WALL### 2 profiles 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 26 . 1 the 2 profiles 2 profiles 3 of 2 profiles 10 and 3 of 8 nodes 4 mesenteric 5 and 5 and 6 pancreatic 5 and 7 lymph 7 lymph 8 nodes 9 differ 10 and 10 and 12 change 10 and 20 cells 11 often 12 change 12 change 13 reciprocally 12 change 15 to 14 due 15 to 15 to 17 migration 16 directed 17 migration 17 migration 18 of 18 of 19 t 20 cells 21 towards 20 cells 24 of 21 towards 23 site 22 the 23 site 24 of 25 inflammation significant events in our colony include early decline in cd4 ( [+] )cd25 [(] + )cd62l ( [+] [ )(treg , accompanied [by] gradual increase in cd4 ( [+] )cd25 ( [+] )foxp3 [(] [+] ) treg in peripheral lymphoid organs and pancreatic [infiltrates] . 0 ###LEFT-WALL### 2 events 0 ###LEFT-WALL### 25 increase 0 ###LEFT-WALL### 45 . 1 significant 2 events 2 events 3 in 2 events 25 increase 3 in 8 decline 4 our 8 decline 5 colony 8 decline 6 include 8 decline 7 early 8 decline 8 decline 9 in 8 decline 22 accompanied 9 in 10 cd4 10 cd4 15 + 11 ( 15 + 13 )cd25 15 + 15 + 16 )cd62l 15 + 21 , 16 )cd62l 20 )(treg 17 ( 20 )(treg 20 )(treg 21 , 22 accompanied 24 gradual 25 increase 26 in 25 increase 37 treg 26 in 27 cd4 27 cd4 30 )cd25 28 ( 30 )cd25 30 )cd25 33 )foxp3 30 )cd25 36 ) 31 ( 33 )foxp3 33 )foxp3 36 ) 37 treg 38 in 38 in 42 and 39 peripheral 41 organs 40 lymphoid 41 organs 41 organs 42 and 42 and 43 pancreatic impressively , aged euglycemic mice display significant transient rise [in] cd4 ( [+] )cd25 [(] - )foxp3 [(] [+] ) treg in the thymus , pancreas and draining lymph nodes . 0 ###LEFT-WALL### 5 mice 0 ###LEFT-WALL### 6 display 0 ###LEFT-WALL### 31 . 1 impressively 2 , 1 impressively 5 mice 3 aged 5 mice 4 euglycemic 5 mice 5 mice 6 display 6 display 21 treg 6 display 22 in 7 significant 9 rise 8 transient 9 rise 9 rise 21 treg 11 cd4 14 )cd25 11 cd4 21 treg 12 ( 14 )cd25 14 )cd25 16 - 17 )foxp3 20 ) 17 )foxp3 21 treg 22 in 27 and 23 the 24 thymus 24 thymus 25 , 25 , 26 pancreas 25 , 27 and 27 and 30 nodes 28 draining 30 nodes 29 lymph 30 nodes a significant difference was superior viability of effector [and] suppressor cells from new onset diabetics in the presence of high interleukin - 2 ( il - 2 ) concentrations in vitro [as] compared to cells of prediabetic mice . 0 ###LEFT-WALL### 3 difference 0 ###LEFT-WALL### 4 was 0 ###LEFT-WALL### 39 . 1 a 2 significant 1 a 3 difference 2 significant 3 difference 3 difference 4 was 4 was 6 viability 5 superior 6 viability 6 viability 7 of 6 viability 12 from 7 of 11 cells 8 effector 10 suppressor 10 suppressor 11 cells 12 from 15 diabetics 13 new 14 onset 14 onset 15 diabetics 15 diabetics 16 in 16 in 18 presence 17 the 18 presence 18 presence 19 of 18 presence 29 concentrations 18 presence 33 compared 19 of 21 interleukin 20 high 21 interleukin 21 interleukin 23 2 22 - 23 2 23 2 26 - 23 2 28 ) 24 ( 26 - 25 il 26 - 26 - 27 2 26 - 28 ) 29 concentrations 33 compared 30 in 31 vitro 31 vitro 33 compared 33 compared 34 to 34 to 35 cells 35 cells 36 of 36 of 38 mice 37 prediabetic 38 mice overall , we found no correlation between foxp3 ( [+] [ )(treg in the pancreatic lymph nodes and the inflammatory scores of individual nod mice . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 found 1 overall 2 , 1 overall 3 we 3 we 4 found 4 found 6 correlation 4 found 7 between 5 no 6 correlation 7 between 8 foxp3 8 foxp3 18 and 9 ( 18 and 12 )(treg 13 in 12 )(treg 18 and 13 in 17 nodes 14 the 17 nodes 15 pancreatic 16 lymph 16 lymph 17 nodes 18 and 25 mice 18 and 26 . 19 the 21 scores 20 inflammatory 21 scores 21 scores 22 of 21 scores 25 mice 22 of 25 mice 23 individual 25 mice 24 nod 25 mice cd25 [(] - )foxp3 ( [+] [ )(treg [are] markedly increased in the pancreatic [infiltrates] in late stages of inflammation , possibly an effort to counteract destructive insulitis . 0 ###LEFT-WALL### 1 cd25 0 ###LEFT-WALL### 3 - 3 - 4 )foxp3 4 )foxp3 8 )(treg 5 ( 8 )(treg 8 )(treg 11 increased 8 )(treg 24 effort 8 )(treg 29 . 10 markedly 11 increased 11 increased 12 in 11 increased 16 in 12 in 14 pancreatic 13 the 14 pancreatic 16 in 18 stages 17 late 18 stages 18 stages 19 of 19 of 20 inflammation 21 , 22 possibly 21 , 24 effort 23 an 24 effort 24 effort 25 to 24 effort 26 counteract 24 effort 29 . 25 to 26 counteract 26 counteract 28 insulitis 27 destructive 28 insulitis considering extensive evidence that treg in aged nod mice are functionally sufficient , quantitative profiling evolves as an unreliable tool to assess mechanism [and] causes of inflammation under baseline conditions . 0 ###LEFT-WALL### 1 considering 0 ###LEFT-WALL### 22 assess 0 ###LEFT-WALL### 31 . 1 considering 3 evidence 1 considering 15 profiling 1 considering 16 evolves 2 extensive 3 evidence 3 evidence 4 that 3 evidence 10 are 4 that 9 mice 4 that 10 are 5 treg 6 in 5 treg 9 mice 6 in 8 nod 7 aged 8 nod 9 mice 10 are 10 are 11 functionally 12 sufficient 13 , 12 sufficient 15 profiling 14 quantitative 15 profiling 16 evolves 17 as 16 evolves 21 to 17 as 20 tool 18 an 19 unreliable 18 an 20 tool 19 unreliable 20 tool 21 to 22 assess 22 assess 25 causes 22 assess 28 under 23 mechanism 25 causes 25 causes 26 of 26 of 27 inflammation 28 under 30 conditions 29 baseline 30 conditions immune profiles are modulated by thymic output , cell migration , shedding of markers , proliferation , survival and [in] [-] [situ] evolution of regulatory cells . 0 ###LEFT-WALL### 2 profiles 0 ###LEFT-WALL### 4 modulated 0 ###LEFT-WALL### 27 . 1 immune 2 profiles 2 profiles 3 are 3 are 4 modulated 4 modulated 5 by 5 by 19 and 6 thymic 7 output 7 output 8 , 8 , 10 migration 8 , 11 , 9 cell 10 migration 11 , 12 shedding 11 , 15 , 12 shedding 13 of 13 of 14 markers 15 , 16 proliferation 15 , 17 , 17 , 18 survival 17 , 19 and 19 and 23 evolution 19 and 24 of 24 of 26 cells 25 regulatory 26 cells among urban - dwelling older african americans who are at elevated risk for cognitive impairment and dementia , we know even less regarding the interaction of these risk factors . 0 ###LEFT-WALL### 28 risk 0 ###LEFT-WALL### 30 . 1 among 7 americans 1 among 28 risk 2 urban 3 - 2 urban 4 dwelling 4 dwelling 7 americans 5 older 6 african 6 african 7 americans 7 americans 8 who 7 americans 9 are 8 who 9 are 9 are 10 at 9 are 23 regarding 10 at 12 risk 11 elevated 12 risk 12 risk 13 for 12 risk 19 we 12 risk 20 know 13 for 16 and 14 cognitive 15 impairment 15 impairment 16 and 16 and 17 dementia 16 and 18 , 19 we 20 know 20 know 22 less 21 even 22 less 23 regarding 25 interaction 24 the 25 interaction 25 interaction 26 of 26 of 27 these 28 risk 29 factors method : five hundred and one african american [elders] ( n=501 ) between the ages of 55 and 95 with an average age of 70.73 years ( sd=8.6 years ) participated in telephone interviews . 0 ###LEFT-WALL### 1 method 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 18 and 0 ###LEFT-WALL### 35 . 1 method 2 : 2 : 8 american 2 : 13 between 3 five 4 hundred 4 hundred 5 and 5 and 6 one 6 one 8 american 7 african 8 american 8 american 11 n=501 10 ( 11 n=501 11 n=501 12 ) 13 between 15 ages 14 the 15 ages 15 ages 16 of 16 of 17 55 18 and 19 95 18 and 31 participated 19 95 20 with 19 95 31 participated 20 with 23 age 21 an 22 average 21 an 23 age 22 average 23 age 23 age 24 of 24 of 26 years 25 70.73 26 years 26 years 29 years 27 ( 29 years 28 sd=8.6 29 years 29 years 30 ) 31 participated 32 in 32 in 34 interviews 33 telephone 34 interviews results : approximately one - third of the elders reported that their memory , thinking skills , or ability to reason was worse than a year [ago] [(] n=150 [;] 29.9 % [ )(and 25 % of this group ( n=38 ) reported that this perceived cognitive impairment impacted their daily activities [and/or] warranted a consultation with their doctor [.] 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 5 - 1 results 2 : 2 : 4 one 3 approximately 4 one 5 - 6 third 5 - 10 reported 6 third 7 of 6 third 10 reported 7 of 9 elders 8 the 9 elders 10 reported 11 that 11 that 13 memory 11 that 22 was 12 their 13 memory 13 memory 15 thinking 13 memory 22 was 14 , 15 thinking 15 thinking 18 or 15 thinking 20 to 16 skills 18 or 17 , 18 or 18 or 19 ability 20 to 21 reason 22 was 23 worse 23 worse 24 than 24 than 29 n=150 25 a 26 year 26 year 29 n=150 29 n=150 34 )(and 31 29.9 32 % 31 29.9 34 )(and 34 )(and 35 25 35 25 36 % 36 % 37 of 36 % 43 reported 37 of 39 group 38 this 39 group 39 group 41 n=38 40 ( 41 n=38 41 n=38 42 ) 43 reported 44 that 44 that 47 cognitive 44 that 54 warranted 45 this 47 cognitive 46 perceived 47 cognitive 47 cognitive 48 impairment 47 cognitive 49 impacted 47 cognitive 54 warranted 48 impairment 49 impacted 49 impacted 52 activities 50 their 52 activities 51 daily 52 activities 54 warranted 56 consultation 55 a 56 consultation 56 consultation 57 with 57 with 59 doctor 58 their 59 doctor bivariate analyses indicated that perceived cognitive impairment was associated with increased health problems , mobility limitations , depressed mood , and lower social functioning . 0 ###LEFT-WALL### 21 and 0 ###LEFT-WALL### 25 . 1 bivariate 9 associated 1 bivariate 10 with 1 bivariate 14 , 2 analyses 3 indicated 3 indicated 4 that 4 that 7 impairment 4 that 9 associated 5 perceived 6 cognitive 6 cognitive 7 impairment 7 impairment 8 was 8 was 9 associated 10 with 13 problems 11 increased 12 health 12 health 13 problems 14 , 16 limitations 14 , 17 , 15 mobility 16 limitations 17 , 19 mood 17 , 21 and 18 depressed 19 mood 20 , 21 and 21 and 23 social 21 and 24 functioning 22 lower 23 social conclusion : elders who reported that cognitive problems impacted their daily functioning reported the greatest health and mental health problems . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 21 . 2 : 3 elders 2 : 13 reported 3 elders 4 who 3 elders 9 impacted 3 elders 13 reported 4 who 8 problems 4 who 9 impacted 5 reported 8 problems 6 that 7 cognitive 7 cognitive 8 problems 8 problems 9 impacted 9 impacted 11 daily 10 their 11 daily 11 daily 12 functioning 13 reported 17 and 14 the 15 greatest 14 the 16 health 16 health 17 and 17 and 20 problems 18 mental 19 health 19 health 20 problems perceived cognitive impairment is an important health variable with implications for an older adult 's overall health , mobility , and mental health . 0 ###LEFT-WALL### 3 impairment 0 ###LEFT-WALL### 4 is 0 ###LEFT-WALL### 24 . 1 perceived 3 impairment 2 cognitive 3 impairment 3 impairment 4 is 4 is 8 variable 5 an 6 important 5 an 8 variable 6 important 7 health 7 health 8 variable 8 variable 9 with 9 with 21 and 10 implications 11 for 10 implications 18 , 11 for 17 health 12 an 14 adult 13 older 14 adult 14 adult 15 's 15 's 17 health 16 overall 17 health 18 , 19 mobility 18 , 21 and 20 , 21 and 21 and 23 health 22 mental 23 health objectives : this longitudinal investigation addressed whether and how lifetime cumulative adversity and depressive symptoms moderated age - related decline in markers of physical , mental , and cognitive health . 0 ###LEFT-WALL### 1 objectives 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 20 decline 0 ###LEFT-WALL### 31 . 2 : 5 investigation 2 : 6 addressed 3 this 4 longitudinal 4 longitudinal 5 investigation 5 investigation 6 addressed 6 addressed 8 and 7 whether 8 and 8 and 9 how 8 and 13 and 8 and 20 decline 10 lifetime 12 adversity 11 cumulative 12 adversity 12 adversity 13 and 13 and 17 age 13 and 18 - 13 and 19 related 13 and 20 decline 14 depressive 17 age 15 symptoms 17 age 16 moderated 17 age 20 decline 21 in 21 in 22 markers 22 markers 23 of 23 of 30 health 24 physical 25 , 24 physical 30 health 26 mental 28 and 27 , 28 and 28 and 29 cognitive 28 and 30 health method : 1248 older adults [(] mean age = 62 at wave 1 [ )(who completed the first two waves of the israeli component of the survey of health , ageing and retirement in europe ( share - israel ) reported on exposure to potentially traumatic life events , depressive symptoms , and three outcomes - disability , quality of life , and cognitive markers . 0 ###LEFT-WALL### 1 method 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 7 mean 2 : 5 adults 3 1248 5 adults 4 older 5 adults 5 adults 7 mean 7 mean 8 age 7 mean 9 = 8 age 9 = 9 = 10 62 10 62 11 at 10 62 15 )(who 10 62 16 completed 10 62 21 of 11 at 12 wave 12 wave 13 1 15 )(who 16 completed 16 completed 20 waves 17 the 20 waves 18 first 20 waves 19 two 20 waves 21 of 32 and 22 the 24 component 23 israeli 24 component 24 component 25 of 24 component 30 , 25 of 27 survey 26 the 27 survey 27 survey 28 of 28 of 29 health 30 , 31 ageing 30 , 32 and 32 and 33 retirement 33 retirement 34 in 33 retirement 41 reported 33 retirement 42 on 34 in 35 europe 35 europe 38 - 36 ( 38 - 37 share 38 - 38 - 39 israel 38 - 40 ) 42 on 53 and 43 exposure 44 to 43 exposure 49 , 44 to 48 events 45 potentially 46 traumatic 46 traumatic 47 life 47 life 48 events 49 , 51 symptoms 49 , 53 and 50 depressive 51 symptoms 52 , 53 and 53 and 55 outcomes 53 and 56 - 53 and 65 markers 54 three 55 outcomes 56 - 65 markers 57 disability 58 , 58 , 59 quality 58 , 63 and 59 quality 60 of 60 of 61 life 62 , 63 and 63 and 64 cognitive 63 and 65 markers 65 markers 66 . results : age was related to greater functional decline [in] outcome measures across the two waves ( i.e [.] , increase in disability and decrease in quality of life and cognitive functioning ) . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 34 . 2 : 3 age 2 : 5 related 2 : 20 , 3 age 4 was 4 was 5 related 5 related 6 to 5 related 13 across 6 to 12 measures 7 greater 9 decline 8 functional 9 decline 9 decline 12 measures 11 outcome 12 measures 13 across 16 waves 14 the 15 two 15 two 16 waves 16 waves 18 i.e 17 ( 18 i.e 18 i.e 20 , 20 , 24 and 21 increase 22 in 21 increase 24 and 22 in 23 disability 24 and 25 decrease 25 decrease 26 in 26 in 27 quality 27 quality 28 of 28 of 30 and 29 life 30 and 30 and 32 functioning 30 and 33 ) 31 cognitive 32 functioning this age [-] related decline became stronger as lifetime adversity increased . 0 ###LEFT-WALL### 5 decline 0 ###LEFT-WALL### 6 became 0 ###LEFT-WALL### 12 . 1 this 5 decline 2 age 4 related 4 related 5 decline 5 decline 6 became 6 became 7 stronger 7 stronger 8 as 8 as 10 adversity 9 lifetime 10 adversity 10 adversity 11 increased [a] three - way interaction showed that the greatest age - related functional decline [in] outcome measures was especially salient among those with high level of lifetime adversity and high level of depressive symptoms . 0 ###LEFT-WALL### 2 three 0 ###LEFT-WALL### 3 - 3 - 5 interaction 3 - 6 showed 3 - 35 . 4 way 5 interaction 5 interaction 6 showed 6 showed 7 that 6 showed 10 age 6 showed 18 was 8 the 9 greatest 8 the 10 age 10 age 18 was 11 - 12 related 12 related 17 measures 12 related 18 was 13 functional 14 decline 14 decline 16 outcome 16 outcome 17 measures 18 was 20 salient 19 especially 20 salient 20 salient 21 among 21 among 29 and 22 those 23 with 22 those 26 of 22 those 29 and 23 with 25 level 24 high 25 level 26 of 28 adversity 27 lifetime 28 adversity 29 and 31 level 29 and 32 of 30 high 31 level 32 of 34 symptoms 33 depressive 34 symptoms conclusion : lifetime cumulative adversity is associated with a more noticeable process of age - related dysfunction across various markers of health . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 3 lifetime 2 : 7 associated 2 : 16 related 2 : 23 . 3 lifetime 5 adversity 3 lifetime 6 is 3 lifetime 7 associated 4 cumulative 5 adversity 5 adversity 6 is 7 associated 8 with 8 with 12 process 9 a 12 process 10 more 11 noticeable 11 noticeable 12 process 12 process 13 of 13 of 14 age 15 - 16 related 16 related 17 dysfunction 16 related 18 across 18 across 20 markers 19 various 20 markers 20 markers 21 of 21 of 22 health although the majority of older adults are resilient to lifetime adversity , prevention and intervention programs should be aimed at mitigating the pronounced senescence observed when adversity accumulated to a large degree , and especially when it is accompanied with high level of distress . 0 ###LEFT-WALL### 37 it 0 ###LEFT-WALL### 45 . 1 although 3 majority 1 although 7 are 1 although 37 it 2 the 3 majority 3 majority 4 of 3 majority 7 are 4 of 6 adults 5 older 6 adults 7 are 34 and 8 resilient 9 to 8 resilient 12 , 9 to 11 adversity 10 lifetime 11 adversity 12 , 13 prevention 12 , 14 and 14 and 15 intervention 14 and 16 programs 14 and 21 mitigating 14 and 34 and 16 programs 17 should 17 should 18 be 18 be 19 aimed 19 aimed 20 at 20 at 21 mitigating 21 mitigating 24 senescence 21 mitigating 26 when 22 the 24 senescence 23 pronounced 24 senescence 24 senescence 25 observed 26 when 27 adversity 26 when 28 accumulated 27 adversity 28 accumulated 28 accumulated 29 to 29 to 32 degree 30 a 32 degree 31 large 32 degree 33 , 34 and 34 and 35 especially 34 and 36 when 37 it 38 is 38 is 39 accompanied 39 accompanied 40 with 40 with 42 level 41 high 42 level 42 level 43 of 43 of 44 distress objectives : the study examined major diatheses and stressors directly related to suicidal ideation among elderly korean immigrants . 0 ###LEFT-WALL### 1 objectives 0 ###LEFT-WALL### 2 : 2 : 4 study 2 : 5 examined 2 : 11 related 3 the 4 study 4 study 5 examined 5 examined 8 and 5 examined 11 related 6 major 7 diatheses 7 diatheses 8 and 8 and 9 stressors 8 and 11 related 10 directly 11 related 11 related 12 to 11 related 15 among 11 related 19 . 12 to 14 ideation 13 suicidal 14 ideation 15 among 18 immigrants 16 elderly 17 korean 17 korean 18 immigrants the study also explored the significant interactions among these factors . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 4 explored 0 ###LEFT-WALL### 11 . 1 the 2 study 2 study 4 explored 3 also 4 explored 4 explored 7 interactions 4 explored 8 among 5 the 7 interactions 6 significant 7 interactions 8 among 10 factors 9 these 10 factors method : data were collected from a cross - sectional survey [of] 220 elderly korean immigrants ( age ≥ 65 ) in los angeles county . 0 ###LEFT-WALL### 1 method 0 ###LEFT-WALL### 2 : 2 : 3 data 2 : 4 were 2 : 26 . 3 data 4 were 4 were 5 collected 5 collected 6 from 5 collected 22 in 6 from 8 cross 7 a 8 cross 8 cross 16 immigrants 9 - 16 immigrants 10 sectional 16 immigrants 11 survey 16 immigrants 13 220 16 immigrants 14 elderly 15 korean 15 korean 16 immigrants 16 immigrants 19 ≥ 16 immigrants 21 ) 17 ( 19 ≥ 18 age 19 ≥ 19 ≥ 20 65 19 ≥ 21 ) 22 in 25 county 23 los 24 angeles 24 angeles 25 county results : using a robust hierarchical regression , the study found that neuroticism and hopelessness were significantly associated with suicidal ideation . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 22 . 2 : 10 study 2 : 11 found 3 using 7 regression 3 using 8 , 3 using 10 study 4 a 5 robust 4 a 7 regression 5 robust 7 regression 6 hierarchical 7 regression 9 the 10 study 10 study 11 found 11 found 12 that 12 that 14 and 12 that 18 associated 13 neuroticism 14 and 14 and 15 hopelessness 14 and 16 were 16 were 18 associated 17 significantly 18 associated 18 associated 19 with 19 with 21 ideation 20 suicidal 21 ideation in addition , two interaction terms - neuroticism by hopelessness and neuroticism by acculturation - were both significant predictor variables with strong explanatory power . 0 ###LEFT-WALL### 6 terms 0 ###LEFT-WALL### 16 were 0 ###LEFT-WALL### 25 . 1 in 2 addition 1 in 3 , 1 in 6 terms 4 two 6 terms 5 interaction 6 terms 6 terms 11 and 6 terms 16 were 7 - 11 and 8 neuroticism 9 by 8 neuroticism 11 and 9 by 10 hopelessness 11 and 12 neuroticism 11 and 13 by 11 and 15 - 13 by 14 acculturation 16 were 20 variables 17 both 20 variables 18 significant 19 predictor 19 predictor 20 variables 20 variables 21 with 21 with 24 power 22 strong 24 power 23 explanatory 24 power conclusion : the theoretical implications as well as the practical implications for developing and implementing late - life suicide prevention strategies are discussed . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 24 . 2 : 5 implications 2 : 14 and 3 the 5 implications 4 theoretical 5 implications 5 implications 8 as 5 implications 12 for 6 as 7 well 7 well 8 as 8 as 11 implications 9 the 11 implications 10 practical 11 implications 12 for 13 developing 14 and 21 strategies 14 and 22 are 15 implementing 18 life 16 late 17 - 16 late 18 life 18 life 21 strategies 19 suicide 20 prevention 20 prevention 21 strategies 21 strategies 22 are 22 are 23 discussed the study also aimed to undertake initial psychometric analysis on two new outcome scales designed to measure knowledge and confidence in dementia care . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 4 aimed 0 ###LEFT-WALL### 24 . 1 the 2 study 2 study 4 aimed 3 also 4 aimed 4 aimed 5 to 4 aimed 10 on 4 aimed 16 to 4 aimed 17 measure 5 to 6 undertake 6 undertake 9 analysis 7 initial 9 analysis 8 psychometric 9 analysis 10 on 14 scales 11 two 14 scales 12 new 13 outcome 13 outcome 14 scales 14 scales 15 designed 16 to 17 measure 17 measure 19 and 17 measure 21 in 18 knowledge 19 and 19 and 20 confidence 21 in 23 care 22 dementia 23 care methods : the study comprised two phases . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 4 study 2 : 5 comprised 2 : 8 . 3 the 4 study 4 study 5 comprised 5 comprised 7 phases 6 two 7 phases the first phase comprised the design of two questionnaires which are shared within this paper : confidence in dementia ( code ) scale and knowledge in dementia ( kide ) scale . 0 ###LEFT-WALL### 3 phase 0 ###LEFT-WALL### 4 comprised 0 ###LEFT-WALL### 16 : 0 ###LEFT-WALL### 32 . 1 the 2 first 1 the 3 phase 3 phase 4 comprised 4 comprised 6 design 5 the 6 design 6 design 7 of 7 of 9 questionnaires 8 two 9 questionnaires 9 questionnaires 10 which 9 questionnaires 11 are 10 which 11 are 11 are 12 shared 12 shared 13 within 13 within 15 paper 14 this 15 paper 16 : 17 confidence 17 confidence 18 in 17 confidence 26 in 18 in 24 and 19 dementia 21 code 20 ( 21 code 21 code 22 ) 21 code 23 scale 23 scale 24 and 24 and 25 knowledge 26 in 31 scale 27 dementia 29 kide 28 ( 29 kide 29 kide 30 ) 29 kide 31 scale in phase two , staff undertook the ['] getting [to] know me ['] training programme ( n=71 ) . 0 ###LEFT-WALL### 5 staff 0 ###LEFT-WALL### 6 undertook 0 ###LEFT-WALL### 19 . 1 in 2 phase 1 in 4 , 1 in 5 staff 2 phase 3 two 5 staff 6 undertook 6 undertook 15 programme 7 the 15 programme 9 getting 11 know 11 know 12 me 12 me 15 programme 14 training 15 programme 15 programme 17 n=71 16 ( 17 n=71 17 n=71 18 ) the impact of the programme was evaluated using a pre - post design which explored : ( 1 ) changes in confidence in dementia [;] ( 2 ) changes in knowledge in dementia [;] [and] ( 3 [ )(changes in beliefs about challenging behaviour . 0 ###LEFT-WALL### 2 impact 0 ###LEFT-WALL### 7 evaluated 0 ###LEFT-WALL### 11 - 1 the 2 impact 2 impact 3 of 2 impact 6 was 3 of 5 programme 4 the 5 programme 6 was 7 evaluated 7 evaluated 8 using 8 using 10 pre 9 a 10 pre 11 - 12 post 11 - 20 changes 12 post 13 design 12 post 16 : 12 post 18 1 12 post 20 changes 13 design 14 which 13 design 15 explored 13 design 16 : 14 which 15 explored 17 ( 18 1 18 1 19 ) 20 changes 21 in 20 changes 30 in 21 in 22 confidence 22 confidence 23 in 23 in 29 changes 24 dementia 27 2 24 dementia 28 ) 24 dementia 29 changes 26 ( 27 2 27 2 28 ) 30 in 31 knowledge 31 knowledge 32 in 32 in 33 dementia 33 dementia 39 )(changes 36 ( 39 )(changes 37 3 39 )(changes 39 )(changes 40 in 39 )(changes 42 about 39 )(changes 45 . 40 in 41 beliefs 42 about 44 behaviour 43 challenging 44 behaviour results : the psychometric properties of the code and kide scales are reported . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 14 . 1 results 2 : 2 : 5 properties 3 the 5 properties 4 psychometric 5 properties 5 properties 6 of 6 of 8 code 7 the 8 code 9 and 11 scales 9 and 13 reported 10 kide 11 scales 11 scales 12 are 12 are 13 reported statistically significant change was identified pre - post training on all outcome measures . 0 ###LEFT-WALL### 3 change 0 ###LEFT-WALL### 4 was 0 ###LEFT-WALL### 14 . 1 statistically 2 significant 2 significant 3 change 3 change 4 was 4 was 9 training 5 identified 8 post 6 pre 7 - 6 pre 8 post 8 post 9 training 9 training 10 on 10 on 13 measures 11 all 13 measures 12 outcome 13 measures clinically meaningful change was demonstrated on the code scale . 0 ###LEFT-WALL### 3 change 0 ###LEFT-WALL### 5 demonstrated 0 ###LEFT-WALL### 10 . 1 clinically 3 change 2 meaningful 3 change 3 change 4 was 4 was 5 demonstrated 5 demonstrated 6 on 6 on 9 scale 7 the 9 scale 8 code 9 scale conclusions : the ['] getting [to] know me ['] programme was well received and had a significant impact on staff knowledge and confidence . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 24 . 2 : 10 programme 2 : 15 had 3 the 10 programme 5 getting 7 know 7 know 8 me 8 me 10 programme 10 programme 11 was 11 was 12 well 12 well 14 and 13 received 14 and 14 and 15 had 15 had 18 impact 16 a 18 impact 17 significant 18 impact 18 impact 19 on 19 on 22 and 20 staff 21 knowledge 21 knowledge 22 and 22 and 23 confidence objectives : the purposes of this study were to explore elderly outpatients ' perceived reasons for , opinions [of] , and suggestions for elderly people considering suicide in taiwan . 0 ###LEFT-WALL### 1 objectives 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 17 , 0 ###LEFT-WALL### 30 . 1 objectives 2 : 2 : 4 purposes 3 the 4 purposes 4 purposes 5 of 4 purposes 7 study 4 purposes 16 for 5 of 6 this 7 study 8 were 8 were 9 to 8 were 10 explore 9 to 10 explore 10 explore 15 reasons 10 explore 16 for 11 elderly 12 outpatients 12 outpatients 13 ' 13 ' 15 reasons 14 perceived 15 reasons 17 , 21 and 18 opinions 21 and 20 , 21 and 21 and 22 suggestions 21 and 23 for 21 and 26 considering 23 for 25 people 24 elderly 25 people 26 considering 27 suicide 26 considering 28 in 28 in 29 taiwan method : elderly outpatients ( n = 83 ) were recruited in 2011 - 2012 by convenience sampling from three randomly selected medical centers in taiwan . 0 ###LEFT-WALL### 1 method 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 18 sampling 0 ###LEFT-WALL### 27 . 2 : 3 elderly 3 elderly 4 outpatients 3 elderly 18 sampling 4 outpatients 7 = 4 outpatients 10 were 5 ( 7 = 6 n 7 = 7 = 8 83 7 = 9 ) 10 were 11 recruited 11 recruited 12 in 11 recruited 16 by 12 in 14 - 13 2011 14 - 14 - 15 2012 16 by 17 convenience 17 convenience 18 sampling 18 sampling 19 from 18 sampling 25 in 19 from 24 centers 20 three 24 centers 21 randomly 22 selected 22 selected 24 centers 23 medical 24 centers 25 in 26 taiwan data were collected in individual interviews using a semi - structured guide and analyzed by content analysis . 0 ###LEFT-WALL### 1 data 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 18 . 1 data 13 and 2 were 3 collected 2 were 13 and 3 collected 4 in 4 in 6 interviews 5 individual 6 interviews 6 interviews 7 using 7 using 12 guide 8 a 9 semi 8 a 12 guide 9 semi 10 - 9 semi 12 guide 11 structured 12 guide 13 and 14 analyzed 13 and 15 by 15 by 17 analysis 16 content 17 analysis results : findings revealed that most participants had heard of elderly suicide , with television news as the main source for their information . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 1 results 2 : 2 : 3 findings 3 findings 4 revealed 3 findings 5 that 5 that 7 participants 5 that 9 heard 6 most 7 participants 7 participants 8 had 8 had 9 heard 9 heard 10 of 9 heard 14 with 10 of 12 suicide 11 elderly 12 suicide 13 , 14 with 14 with 16 news 14 with 24 . 15 television 16 news 16 news 17 as 16 news 21 for 17 as 20 source 18 the 19 main 18 the 20 source 21 for 23 information 22 their 23 information their opinions about elderly suicide reflected judgmental attitudes , negative emotional reactions , expectations of social welfare , and could happen after losing one 's meaning in life . 0 ###LEFT-WALL### 2 opinions 0 ###LEFT-WALL### 19 and 0 ###LEFT-WALL### 29 . 1 their 2 opinions 2 opinions 3 about 2 opinions 19 and 3 about 5 suicide 4 elderly 5 suicide 6 reflected 8 attitudes 6 reflected 19 and 7 judgmental 8 attitudes 8 attitudes 12 reactions 9 , 12 reactions 10 negative 12 reactions 11 emotional 12 reactions 12 reactions 14 expectations 12 reactions 18 , 13 , 14 expectations 14 expectations 15 of 14 expectations 18 , 15 of 17 welfare 16 social 17 welfare 19 and 20 could 19 and 22 after 19 and 27 in 20 could 21 happen 22 after 23 losing 23 losing 26 meaning 24 one 25 's 25 's 26 meaning 27 in 28 life their suggestions for elderly people considering suicide fell into four major themes : give up suicidal ideas , seek help , enhance social welfare , and attend religious activities . 0 ###LEFT-WALL### 2 suggestions 0 ###LEFT-WALL### 8 fell 0 ###LEFT-WALL### 13 : 1 their 2 suggestions 2 suggestions 3 for 2 suggestions 8 fell 3 for 5 people 4 elderly 5 people 5 people 6 considering 6 considering 7 suicide 8 fell 9 into 9 into 12 themes 10 four 12 themes 11 major 12 themes 13 : 18 , 13 : 30 . 14 give 15 up 14 give 17 ideas 14 give 18 , 16 suicidal 17 ideas 18 , 21 , 19 seek 20 help 19 seek 21 , 21 , 26 and 22 enhance 24 welfare 22 enhance 26 and 23 social 24 welfare 25 , 26 and 26 and 27 attend 27 attend 29 activities 28 religious 29 activities conclusion : since television news was the main source for participants ' information about elderly suicide , this mass medium should be used in suicide prevention to disseminate suicide knowledge , increase access to help , and strengthen suicide - protective factors among the elderly . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 46 . 2 : 20 medium 2 : 23 used 2 : 31 , 3 since 5 news 3 since 6 was 3 since 17 , 3 since 20 medium 4 television 5 news 5 news 6 was 6 was 9 source 7 the 9 source 8 main 9 source 9 source 10 for 9 source 14 about 10 for 13 information 11 participants 12 ' 12 ' 13 information 14 about 16 suicide 15 elderly 16 suicide 18 this 20 medium 19 mass 20 medium 20 medium 21 should 21 should 22 be 22 be 23 used 23 used 24 in 23 used 27 to 23 used 28 disseminate 24 in 26 prevention 25 suicide 26 prevention 27 to 28 disseminate 28 disseminate 30 knowledge 29 suicide 30 knowledge 31 , 32 increase 31 , 40 - 32 increase 33 access 32 increase 34 to 34 to 37 and 35 help 37 and 36 , 37 and 37 and 38 strengthen 38 strengthen 39 suicide 40 - 42 factors 41 protective 42 factors 42 factors 43 among 43 among 45 elderly 44 the 45 elderly furthermore , no participants mentioned depression as a reason for attempted or completed suicide among older people despite depression being a well - known suicide - risk factor . 0 ###LEFT-WALL### 4 participants 0 ###LEFT-WALL### 5 mentioned 0 ###LEFT-WALL### 26 - 0 ###LEFT-WALL### 29 . 1 furthermore 2 , 1 furthermore 4 participants 3 no 4 participants 4 participants 5 mentioned 5 mentioned 6 depression 5 mentioned 7 as 5 mentioned 10 for 7 as 9 reason 8 a 9 reason 10 for 12 or 11 attempted 12 or 12 or 13 completed 13 completed 14 suicide 13 completed 15 among 13 completed 18 despite 15 among 17 people 16 older 17 people 18 despite 19 depression 19 depression 20 being 20 being 22 well 21 a 22 well 22 well 25 suicide 23 - 25 suicide 24 known 25 suicide 25 suicide 26 - 26 - 28 factor 27 risk 28 factor future suicide - prevention programs should emphasize the role of depression in suicide among older people . 0 ###LEFT-WALL### 2 suicide 0 ###LEFT-WALL### 3 - 1 future 2 suicide 3 - 5 programs 3 - 7 emphasize 3 - 17 . 4 prevention 5 programs 5 programs 6 should 6 should 7 emphasize 7 emphasize 9 role 7 emphasize 12 in 7 emphasize 14 among 8 the 9 role 9 role 10 of 10 of 11 depression 12 in 13 suicide 14 among 16 people 15 older 16 people participants also did not suggest that older people considering suicide seek help from the health system . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 5 suggest 0 ###LEFT-WALL### 17 . 1 participants 3 did 2 also 3 did 3 did 4 not 3 did 5 suggest 5 suggest 6 that 6 that 8 people 6 that 11 seek 7 older 8 people 8 people 9 considering 9 considering 10 suicide 11 seek 12 help 12 help 13 from 13 from 16 system 14 the 16 system 15 health 16 system thus , older people should be educated about the role of the health system in suicide prevention and trained as gatekeepers to recognize signs of suicide ideation and respond appropriately . 0 ###LEFT-WALL### 4 people 0 ###LEFT-WALL### 18 and 0 ###LEFT-WALL### 31 . 1 thus 2 , 1 thus 4 people 3 older 4 people 4 people 5 should 5 should 18 and 6 be 7 educated 6 be 18 and 7 educated 8 about 7 educated 15 in 8 about 10 role 9 the 10 role 10 role 11 of 11 of 14 system 12 the 14 system 13 health 14 system 15 in 17 prevention 16 suicide 17 prevention 18 and 19 trained 18 and 20 as 18 and 22 to 20 as 21 gatekeepers 22 to 28 and 23 recognize 24 signs 23 recognize 28 and 24 signs 25 of 25 of 27 ideation 26 suicide 27 ideation 28 and 29 respond 29 respond 30 appropriately with the passage of the affordable care act and [as] the number of aging and diverse individuals in society increases , access to health care will expand and the need for more competent and diverse nursing graduates will increase . 0 ###LEFT-WALL### 15 and 0 ###LEFT-WALL### 21 , 0 ###LEFT-WALL### 40 . 1 with 3 passage 1 with 15 and 2 the 3 passage 3 passage 4 of 4 of 7 care 5 the 7 care 6 affordable 7 care 8 act 9 and 9 and 12 number 9 and 15 and 11 the 12 number 12 number 13 of 13 of 14 aging 15 and 17 individuals 15 and 21 , 16 diverse 17 individuals 17 individuals 18 in 18 in 19 society 20 increases 21 , 21 , 28 and 22 access 23 to 22 access 26 will 23 to 25 care 24 health 25 care 26 will 28 and 27 expand 28 and 28 and 39 increase 29 the 30 need 30 need 31 for 30 need 38 will 31 for 37 graduates 32 more 37 graduates 33 competent 34 and 34 and 35 diverse 34 and 36 nursing 36 nursing 37 graduates 38 will 39 increase an adequate number of nurse graduates is imperative to meet societal demands ; however , this is complicated by high nursing student attrition rates . 0 ###LEFT-WALL### 3 number 0 ###LEFT-WALL### 10 meet 0 ###LEFT-WALL### 13 ; 0 ###LEFT-WALL### 25 . 1 an 2 adequate 1 an 3 number 2 adequate 3 number 3 number 4 of 3 number 7 is 4 of 6 graduates 5 nurse 6 graduates 7 is 8 imperative 8 imperative 9 to 9 to 10 meet 10 meet 12 demands 11 societal 12 demands 13 ; 16 this 13 ; 18 complicated 14 however 15 , 14 however 16 this 16 this 17 is 17 is 18 complicated 18 complicated 19 by 19 by 24 rates 20 high 21 nursing 21 nursing 24 rates 22 student 24 rates 23 attrition 24 rates this article examines the need for more nurses ( including those from diverse backgrounds ) , current attrition rates among schools of nursing , at [-] risk student characteristics , and previous attempts to increase student success . 0 ###LEFT-WALL### 2 article 0 ###LEFT-WALL### 3 examines 0 ###LEFT-WALL### 38 . 1 this 2 article 2 article 3 examines 3 examines 5 need 3 examines 25 at 3 examines 34 to 4 the 5 need 5 need 6 for 6 for 8 nurses 7 more 8 nurses 8 nurses 10 including 8 nurses 19 rates 9 ( 10 including 10 including 11 those 10 including 12 from 10 including 15 ) 12 from 14 backgrounds 13 diverse 14 backgrounds 16 , 19 rates 17 current 18 attrition 18 attrition 19 rates 19 rates 20 among 19 rates 22 of 19 rates 24 , 20 among 21 schools 22 of 23 nursing 25 at 31 and 27 risk 29 characteristics 28 student 29 characteristics 29 characteristics 31 and 30 , 31 and 31 and 33 attempts 32 previous 33 attempts 34 to 35 increase 35 increase 37 success 36 student 37 success applying the evidence to practice , findings from a multipronged approach to increase student success within an associate degree nursing program located within a [historically] black college and university in the midwestern united states are discussed . 0 ###LEFT-WALL### 7 findings 0 ###LEFT-WALL### 36 discussed 0 ###LEFT-WALL### 37 . 1 applying 3 evidence 1 applying 4 to 1 applying 6 , 1 applying 7 findings 2 the 3 evidence 4 to 5 practice 7 findings 8 from 7 findings 16 within 7 findings 35 are 8 from 11 approach 9 a 11 approach 10 multipronged 11 approach 11 approach 12 to 12 to 15 success 13 increase 15 success 14 student 15 success 16 within 28 and 17 an 21 program 18 associate 21 program 19 degree 21 program 20 nursing 21 program 21 program 22 located 21 program 28 and 22 located 23 within 23 within 27 college 24 a 27 college 26 black 27 college 28 and 29 university 28 and 30 in 30 in 34 states 31 the 34 states 32 midwestern 34 states 33 united 34 states 35 are 36 discussed the program 's successes and opportunities for improvement are examined , as well as the recommendations for other nursing programs facing issues with student attrition . 0 ###LEFT-WALL### 5 and 0 ###LEFT-WALL### 10 examined 0 ###LEFT-WALL### 11 , 0 ###LEFT-WALL### 26 . 1 the 2 program 2 program 3 's 3 's 4 successes 4 successes 5 and 5 and 6 opportunities 5 and 9 are 6 opportunities 7 for 7 for 8 improvement 9 are 10 examined 11 , 21 facing 11 , 22 issues 12 as 13 well 12 as 21 facing 14 as 16 recommendations 14 as 21 facing 15 the 16 recommendations 16 recommendations 17 for 17 for 20 programs 18 other 20 programs 19 nursing 20 programs 21 facing 22 issues 22 issues 23 with 23 with 25 attrition 24 student 25 attrition none background : although aesthetic correction of facial aging had long been the exclusive domain of plastic surgeons and dermatologists , alternative nonmedical approaches to facial rejuvenation are becoming more popular , such as facial acupuncture , facial acupressure , and facial exercises . 0 ###LEFT-WALL### 1 none 0 ###LEFT-WALL### 28 are 0 ###LEFT-WALL### 44 . 1 none 2 background 1 none 3 : 1 none 28 are 2 background 3 : 3 : 4 although 3 : 25 to 4 although 6 correction 4 although 12 been 5 aesthetic 6 correction 6 correction 7 of 6 correction 10 had 7 of 9 aging 8 facial 9 aging 10 had 12 been 11 long 12 been 12 been 24 approaches 13 the 15 domain 14 exclusive 15 domain 15 domain 16 of 15 domain 19 and 16 of 18 surgeons 17 plastic 18 surgeons 19 and 20 dermatologists 19 and 21 , 19 and 22 alternative 22 alternative 24 approaches 23 nonmedical 24 approaches 25 to 27 rejuvenation 26 facial 27 rejuvenation 28 are 29 becoming 29 becoming 43 exercises 30 more 43 exercises 31 popular 36 acupuncture 31 popular 43 exercises 32 , 36 acupuncture 33 such 36 acupuncture 34 as 35 facial 35 facial 36 acupuncture 36 acupuncture 37 , 38 facial 43 exercises 39 acupressure 41 and 40 , 41 and 41 and 42 facial 41 and 43 exercises however , the effectiveness of these alternative approaches is still a topic of debate . 0 ###LEFT-WALL### 4 effectiveness 0 ###LEFT-WALL### 9 is 0 ###LEFT-WALL### 15 . 1 however 2 , 1 however 4 effectiveness 3 the 4 effectiveness 4 effectiveness 5 of 4 effectiveness 9 is 5 of 8 approaches 6 these 8 approaches 7 alternative 8 approaches 9 is 10 still 9 is 12 topic 11 a 12 topic 12 topic 13 of 13 of 14 debate objectives : the authors review the evidence of the effectiveness of facial exercises for facial rejuvenation . 0 ###LEFT-WALL### 1 objectives 0 ###LEFT-WALL### 2 : 2 : 4 authors 2 : 5 review 2 : 17 . 3 the 4 authors 4 authors 5 review 5 review 7 evidence 6 the 7 evidence 7 evidence 8 of 8 of 10 effectiveness 9 the 10 effectiveness 10 effectiveness 11 of 11 of 13 exercises 12 facial 13 exercises 13 exercises 14 for 14 for 16 rejuvenation 15 facial 16 rejuvenation methods : a literature search was performed in medline , web of science , science direct , scielo , and lilacs databases for the terms facial rejuvenation , facial exercises , facial massage , face building , face yoga , ( oro )facial ( a )esthetics , ( a )esthetic logopedics , and [(] a )esthetic speech [therapy] . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 5 search 2 : 7 performed 2 : 28 , 3 a 5 search 4 literature 5 search 5 search 6 was 6 was 7 performed 7 performed 8 in 7 performed 23 for 8 in 20 and 9 medline 10 , 10 , 11 web 10 , 20 and 11 web 12 of 12 of 13 science 13 science 16 direct 13 science 18 scielo 14 , 16 direct 15 science 16 direct 16 direct 17 , 17 , 18 scielo 18 scielo 19 , 20 and 22 databases 21 lilacs 22 databases 23 for 27 rejuvenation 24 the 27 rejuvenation 25 terms 26 facial 26 facial 27 rejuvenation 28 , 30 exercises 28 , 31 , 29 facial 30 exercises 31 , 33 massage 31 , 34 , 32 facial 33 massage 34 , 35 face 35 face 36 building 36 building 39 yoga 36 building 43 )facial 37 , 39 yoga 38 face 39 yoga 39 yoga 40 , 41 ( 43 )facial 42 oro 43 )facial 43 )facial 46 )esthetics 43 )facial 57 speech 43 )facial 59 . 44 ( 46 )esthetics 45 a 46 )esthetics 46 )esthetics 47 , 48 ( 57 speech 49 a 57 speech 50 )esthetic 51 logopedics 51 logopedics 53 and 52 , 53 and 53 and 56 )esthetic 53 and 57 speech 55 a 56 )esthetic 57 speech 59 . nine reports were identified from the search and were subject to further assessment . 0 ###LEFT-WALL### 2 reports 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 14 . 1 nine 2 reports 2 reports 8 and 3 were 4 identified 3 were 8 and 4 identified 5 from 5 from 7 search 6 the 7 search 8 and 9 were 9 were 10 subject 10 subject 11 to 10 subject 12 further 11 to 12 further 12 further 13 assessment results : although positive outcomes were achieved in all 9 studies , none of the studies used a control group and randomization process . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 24 . 2 : 16 studies 2 : 17 used 3 although 5 outcomes 3 although 7 achieved 3 although 12 , 3 although 16 studies 4 positive 5 outcomes 5 outcomes 6 were 6 were 7 achieved 7 achieved 8 in 8 in 11 studies 9 all 10 9 10 9 11 studies 13 none 14 of 13 none 16 studies 14 of 16 studies 15 the 16 studies 16 studies 17 used 17 used 21 and 18 a 20 group 19 control 20 group 20 group 21 and 21 and 23 process 22 randomization 23 process they were single case reports , small case series , or studies with a single - group pretest - posttest design . 0 ###LEFT-WALL### 1 they 0 ###LEFT-WALL### 2 were 0 ###LEFT-WALL### 6 , 1 they 2 were 2 were 5 reports 3 single 5 reports 4 case 5 reports 6 , 11 or 6 , 18 pretest 6 , 19 - 7 small 8 case 8 case 9 series 9 series 11 or 10 , 11 or 11 or 12 studies 11 or 13 with 11 or 18 pretest 13 with 17 group 14 a 15 single 14 a 17 group 15 single 16 - 15 single 17 group 19 - 21 design 19 - 22 . 20 posttest 21 design moreover , the effectiveness assessments in most of the studies were purely subjective , carried out by the authors [and/or] the patients themselves , without blinding . 0 ###LEFT-WALL### 5 assessments 0 ###LEFT-WALL### 14 , 1 moreover 2 , 1 moreover 5 assessments 3 the 5 assessments 4 effectiveness 5 assessments 5 assessments 6 in 5 assessments 14 , 6 in 10 studies 7 most 8 of 7 most 10 studies 8 of 10 studies 9 the 10 studies 11 were 13 subjective 11 were 14 , 12 purely 13 subjective 14 , 15 carried 15 carried 16 out 15 carried 17 by 15 carried 22 patients 15 carried 23 themselves 15 carried 25 without 17 by 19 authors 18 the 19 authors 21 the 22 patients 24 , 25 without 25 without 26 blinding 25 without 27 . conclusions : the evidence to date is insufficient to determine whether facial exercises are effective for facial rejuvenation . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 4 evidence 2 : 7 is 2 : 19 . 3 the 4 evidence 4 evidence 6 date 4 evidence 7 is 5 to 6 date 7 is 8 insufficient 8 insufficient 9 to 9 to 10 determine 10 determine 11 whether 11 whether 13 exercises 11 whether 14 are 12 facial 13 exercises 13 exercises 14 are 14 are 15 effective 15 effective 16 for 16 for 18 rejuvenation 17 facial 18 rejuvenation evidence from large randomized controlled trials will be needed before conclusions can be drawn . 0 ###LEFT-WALL### 1 evidence 0 ###LEFT-WALL### 9 needed 0 ###LEFT-WALL### 15 . 1 evidence 2 from 1 evidence 7 will 2 from 6 trials 3 large 6 trials 4 randomized 6 trials 5 controlled 6 trials 7 will 8 be 8 be 9 needed 9 needed 10 before 10 before 11 conclusions 10 before 14 drawn 11 conclusions 12 can 12 can 13 be 13 be 14 drawn background : early identification of treatment failure for nosocomial pneumonia remains a major challenge . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 4 identification 2 : 11 remains 2 : 15 . 3 early 4 identification 4 identification 5 of 4 identification 11 remains 5 of 7 failure 6 treatment 7 failure 7 failure 8 for 8 for 10 pneumonia 9 nosocomial 10 pneumonia 11 remains 14 challenge 12 a 13 major 12 a 14 challenge 13 major 14 challenge the goal of this study was to test whether procalcitonin kinetics can be used to assess the clinical efficacy in older critically ill patients with nosocomial pneumonia . 0 ###LEFT-WALL### 2 goal 0 ###LEFT-WALL### 14 used 0 ###LEFT-WALL### 28 . 1 the 2 goal 2 goal 3 of 2 goal 6 was 3 of 5 study 4 this 5 study 6 was 7 to 6 was 14 used 7 to 8 test 8 test 9 whether 8 test 13 be 9 whether 10 procalcitonin 9 whether 11 kinetics 9 whether 12 can 10 procalcitonin 11 kinetics 12 can 13 be 14 used 15 to 14 used 16 assess 15 to 16 assess 16 assess 19 efficacy 16 assess 20 in 16 assess 25 with 17 the 19 efficacy 18 clinical 19 efficacy 20 in 24 patients 21 older 24 patients 22 critically 23 ill 23 ill 24 patients 25 with 27 pneumonia 26 nosocomial 27 pneumonia methods : a prospective observational study was conducted with 60 subjects ( ≥ 65 [y] [old] ) admitted to the icu with severe nosocomial pneumonia . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 6 study 2 : 8 conducted 2 : 18 admitted 2 : 26 . 3 a 6 study 4 prospective 6 study 5 observational 6 study 6 study 7 was 7 was 8 conducted 8 conducted 9 with 9 with 10 60 11 subjects 13 ≥ 11 subjects 18 admitted 12 ( 13 ≥ 13 ≥ 14 65 13 ≥ 17 ) 18 admitted 19 to 18 admitted 22 with 19 to 21 icu 20 the 21 icu 22 with 25 pneumonia 23 severe 25 pneumonia 24 nosocomial 25 pneumonia serum procalcitonin was measured on days 0 , 3 , and [7] [and] at the end of treatment . 0 ###LEFT-WALL### 2 procalcitonin 0 ###LEFT-WALL### 3 was 0 ###LEFT-WALL### 19 . 1 serum 2 procalcitonin 2 procalcitonin 3 was 3 was 4 measured 4 measured 11 and 5 on 6 days 5 on 11 and 6 days 7 0 6 days 9 3 8 , 9 3 9 3 10 , 10 , 11 and 11 and 14 at 14 at 16 end 15 the 16 end 16 end 17 of 17 of 18 treatment the procalcitonin time course was analyzed according to the therapeutic efficacy . 0 ###LEFT-WALL### 4 course 0 ###LEFT-WALL### 6 analyzed 0 ###LEFT-WALL### 12 . 1 the 4 course 2 procalcitonin 4 course 3 time 4 course 4 course 5 was 5 was 6 analyzed 6 analyzed 8 to 7 according 8 to 8 to 11 efficacy 9 the 11 efficacy 10 therapeutic 11 efficacy results : procalcitonin levels were elevated in all subjects ( n = 60 ) on day 0 , and the median level ( range ) was 2.5 ( 0.8 - 42.7 ) μg/l . there were no differences in procalcitonin between the improved subjects ( n = 41 ) and those without improvement ( n = 19 ) on day 0 ( p > [.] 05 ) . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 4 levels 2 : 6 elevated 2 : 19 and 2 : 34 . 3 procalcitonin 4 levels 4 levels 5 were 5 were 6 elevated 6 elevated 7 in 6 elevated 12 = 6 elevated 15 on 7 in 9 subjects 8 all 9 subjects 10 ( 12 = 11 n 12 = 12 = 13 60 12 = 14 ) 15 on 16 day 16 day 17 0 18 , 19 and 19 and 22 level 19 and 26 was 20 the 22 level 21 median 22 level 22 level 24 range 22 level 26 was 23 ( 24 range 24 range 25 ) 26 was 33 μg/l 27 2.5 33 μg/l 28 ( 30 - 29 0.8 30 - 30 - 31 42.7 30 - 32 ) 30 - 33 μg/l 34 . 35 there 34 . 68 . 35 there 36 were 36 were 38 differences 36 were 39 in 37 no 38 differences 39 in 50 and 40 procalcitonin 41 between 40 procalcitonin 50 and 41 between 44 subjects 42 the 44 subjects 43 improved 44 subjects 44 subjects 47 = 45 ( 47 = 46 n 47 = 47 = 48 41 47 = 49 ) 50 and 51 those 50 and 67 ) 51 those 52 without 51 those 59 on 52 without 53 improvement 53 improvement 56 = 54 ( 56 = 55 n 56 = 56 = 57 19 56 = 58 ) 59 on 60 day 60 day 61 0 60 day 64 > 62 ( 64 > 63 p 64 > 64 > 66 05 however , lower procalcitonin levels on days 3 and 7 and at the end of treatment ( all p < [.] [05] ) and greater rates of procalcitonin decline between days 0 and 3 ( δpct ( d3 ) [%] [;] [29.5] ± 10.8 % vs 15.1 ± 5.9 % , p = [.] 009 ) were observed in the improved subjects compared with those with no improvement [.] 0 ###LEFT-WALL### 3 lower 1 however 2 , 1 however 3 lower 3 lower 5 levels 3 lower 11 and 4 procalcitonin 5 levels 6 on 7 days 6 on 11 and 7 days 9 and 8 3 9 and 9 and 10 7 11 and 12 at 12 at 24 and 13 the 14 end 14 end 15 of 14 end 24 and 15 of 16 treatment 16 treatment 18 all 17 ( 18 all 18 all 19 p 18 all 20 < 18 all 23 ) 19 p 20 < 24 and 26 rates 24 and 30 between 25 greater 26 rates 26 rates 27 of 27 of 29 decline 28 procalcitonin 29 decline 30 between 31 days 31 days 33 and 31 days 43 ± 32 0 33 and 33 and 34 3 33 and 36 δpct 33 and 43 ± 35 ( 36 δpct 36 δpct 38 d3 36 δpct 39 ) 37 ( 38 d3 38 d3 39 ) 43 ± 45 % 44 10.8 45 % 45 % 46 vs 46 vs 47 15.1 47 15.1 48 ± 47 15.1 58 observed 48 ± 50 % 48 ± 57 were 48 ± 58 observed 49 5.9 50 % 50 % 53 = 50 % 57 were 51 , 53 = 52 p 53 = 53 = 55 009 53 = 56 ) 58 observed 59 in 58 observed 64 with 58 observed 66 with 59 in 62 subjects 60 the 62 subjects 61 improved 62 subjects 62 subjects 63 compared 64 with 65 those 66 with 68 improvement 67 no 68 improvement δpct ( d3 ) [%] was the best single predictor of efficacy ( area under the curve of 0.79 , p < [.] 001 ) and had a sensitivity of 75.7 % and a specificity of 72.0 % with a threshold of 26.2 % . 0 ###LEFT-WALL### 1 δpct 0 ###LEFT-WALL### 26 and 0 ###LEFT-WALL### 45 . 1 δpct 3 d3 1 δpct 26 and 2 ( 3 d3 3 d3 4 ) 6 was 10 predictor 6 was 26 and 7 the 8 best 7 the 10 predictor 9 single 10 predictor 10 predictor 11 of 11 of 12 efficacy 12 efficacy 14 area 12 efficacy 22 < 13 ( 14 area 14 area 15 under 14 area 20 , 15 under 17 curve 16 the 17 curve 17 curve 18 of 18 of 19 0.79 20 , 22 < 21 p 22 < 22 < 24 001 22 < 25 ) 26 and 27 had 26 and 39 with 27 had 33 and 28 a 29 sensitivity 29 sensitivity 30 of 29 sensitivity 33 and 30 of 32 % 31 75.7 32 % 33 and 35 specificity 33 and 36 of 34 a 35 specificity 36 of 38 % 37 72.0 38 % 39 with 41 threshold 40 a 41 threshold 41 threshold 42 of 42 of 44 % 43 26.2 44 % by comparison , traditional parameters and absolute procalcitonin failed to predict treatment response [(] p > . 05 [ )( 0 ###LEFT-WALL### 1 by 0 ###LEFT-WALL### 16 > 0 ###LEFT-WALL### 17 . 1 by 6 and 1 by 16 > 2 comparison 3 , 3 , 5 parameters 3 , 6 and 4 traditional 5 parameters 6 and 8 procalcitonin 6 and 9 failed 7 absolute 8 procalcitonin 10 to 11 predict 10 to 16 > 11 predict 13 response 12 treatment 13 response 13 response 15 p 17 . 18 05 17 . 20 )( indeed , the combination of δpct ( d3 ) % > 26.2 % and a modified clinical pulmonary infection score of < 6 points improved the predictive value ( area under the curve of 0.89 , sensitivity of 81.3 % , specificity of 86.5 % ) . 0 ###LEFT-WALL### 4 combination 0 ###LEFT-WALL### 11 > 0 ###LEFT-WALL### 14 and 0 ###LEFT-WALL### 47 . 1 indeed 2 , 1 indeed 4 combination 3 the 4 combination 4 combination 5 of 4 combination 11 > 5 of 10 % 6 δpct 8 d3 6 δpct 10 % 7 ( 8 d3 8 d3 9 ) 11 > 13 % 12 26.2 13 % 14 and 20 score 14 and 25 improved 15 a 20 score 16 modified 20 score 17 clinical 18 pulmonary 18 pulmonary 19 infection 19 infection 20 score 20 score 21 of 20 score 25 improved 21 of 24 points 22 < 23 6 23 6 24 points 25 improved 28 value 26 the 28 value 27 predictive 28 value 28 value 30 area 28 value 37 sensitivity 28 value 42 specificity 29 ( 30 area 30 area 31 under 30 area 34 of 30 area 36 , 31 under 33 curve 32 the 33 curve 34 of 35 0.89 36 , 37 sensitivity 37 sensitivity 38 of 37 sensitivity 41 , 38 of 40 % 39 81.3 40 % 41 , 42 specificity 42 specificity 43 of 42 specificity 46 ) 43 of 45 % 44 86.5 45 % conclusions : procalcitonin levels were not influenced by aging , and procalcitonin kinetics might help to identify treatment failure . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 15 help 0 ###LEFT-WALL### 20 . 2 : 3 procalcitonin 3 procalcitonin 4 levels 3 procalcitonin 15 help 4 levels 11 and 5 were 6 not 5 were 7 influenced 5 were 11 and 7 influenced 8 by 8 by 9 aging 10 , 11 and 11 and 15 help 12 procalcitonin 13 kinetics 13 kinetics 14 might 14 might 15 help 15 help 16 to 15 help 17 identify 16 to 17 identify 17 identify 19 failure 18 treatment 19 failure δpct ( d3 ) [%] [in] [combination] with the clinical pulmonary infection score has been shown to be a marker of clinical efficacy at an earlier stage . 0 ###LEFT-WALL### 13 score 0 ###LEFT-WALL### 16 shown 0 ###LEFT-WALL### 28 . 1 δpct 13 score 2 ( 3 d3 3 d3 4 ) 3 d3 13 score 8 with 12 infection 8 with 13 score 9 the 12 infection 10 clinical 11 pulmonary 11 pulmonary 12 infection 13 score 14 has 14 has 15 been 15 been 16 shown 16 shown 17 to 16 shown 24 at 17 to 18 be 18 be 20 marker 19 a 20 marker 20 marker 21 of 21 of 23 efficacy 22 clinical 23 efficacy 24 at 27 stage 25 an 27 stage 26 earlier 27 stage in recent years , a constant growth of knowledge and clinical applications of stem cells have been observed . 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 18 observed 0 ###LEFT-WALL### 19 . 1 in 3 years 1 in 4 , 1 in 10 and 2 recent 3 years 5 a 6 constant 5 a 7 growth 6 constant 7 growth 7 growth 8 of 7 growth 10 and 8 of 9 knowledge 10 and 12 applications 10 and 13 of 10 and 16 have 11 clinical 12 applications 13 of 15 cells 14 stem 15 cells 16 have 17 been 17 been 18 observed mesenchymal stromal cells , also described as mesenchymal stem cells ( mscs ) represent a particular cell type for research and therapy because of their ability to differentiate into mesodermal lineage cells . 0 ###LEFT-WALL### 3 cells 0 ###LEFT-WALL### 14 represent 0 ###LEFT-WALL### 33 . 1 mesenchymal 3 cells 2 stromal 3 cells 3 cells 10 cells 3 cells 14 represent 4 , 5 also 4 , 10 cells 6 described 9 stem 7 as 8 mesenchymal 8 mesenchymal 9 stem 9 stem 10 cells 10 cells 12 mscs 10 cells 13 ) 11 ( 12 mscs 12 mscs 13 ) 14 represent 18 type 14 represent 24 of 14 represent 29 into 15 a 18 type 16 particular 17 cell 17 cell 18 type 18 type 19 for 19 for 21 and 20 research 21 and 21 and 22 therapy 23 because 24 of 24 of 26 ability 25 their 26 ability 26 ability 27 to 26 ability 28 differentiate 27 to 28 differentiate 29 into 32 cells 30 mesodermal 31 lineage 31 lineage 32 cells the most investigated source of mscs is bone marrow ( bm ) . 0 ###LEFT-WALL### 4 source 0 ###LEFT-WALL### 7 is 0 ###LEFT-WALL### 13 . 1 the 4 source 2 most 3 investigated 3 investigated 4 source 4 source 5 of 4 source 7 is 5 of 6 mscs 7 is 9 marrow 8 bone 9 marrow 9 marrow 11 bm 10 ( 11 bm 11 bm 12 ) yet , collection [of] bm is an invasive procedure associated with significant discomfort to the patient . 0 ###LEFT-WALL### 5 bm 0 ###LEFT-WALL### 6 is 0 ###LEFT-WALL### 17 . 1 yet 2 , 1 yet 5 bm 3 collection 5 bm 5 bm 6 is 6 is 9 procedure 7 an 8 invasive 7 an 9 procedure 8 invasive 9 procedure 9 procedure 10 associated 10 associated 11 with 10 associated 14 to 11 with 13 discomfort 12 significant 13 discomfort 14 to 16 patient 15 the 16 patient the procedure results in a relatively low number of these cells , which can decrease with donor ['s] age . 0 ###LEFT-WALL### 2 procedure 0 ###LEFT-WALL### 3 results 0 ###LEFT-WALL### 12 , 0 ###LEFT-WALL### 20 . 1 the 2 procedure 2 procedure 3 results 3 results 4 in 4 in 11 cells 5 a 8 number 6 relatively 7 low 7 low 8 number 8 number 9 of 8 number 11 cells 9 of 11 cells 10 these 11 cells 12 , 13 which 12 , 15 decrease 13 which 14 can 14 can 15 decrease 15 decrease 16 with 16 with 19 age 17 donor 19 age therefore , it seems to be very important to find other sources of mesenchymal stem cells nowadays . 0 ###LEFT-WALL### 3 it 0 ###LEFT-WALL### 4 seems 0 ###LEFT-WALL### 18 . 1 therefore 2 , 1 therefore 3 it 3 it 4 seems 4 seems 5 to 4 seems 6 be 5 to 6 be 6 be 8 important 7 very 8 important 8 important 9 to 8 important 10 find 9 to 10 find 10 find 12 sources 10 find 17 nowadays 11 other 12 sources 12 sources 13 of 13 of 16 cells 14 mesenchymal 15 stem 15 stem 16 cells [a] human placenta , which is routinely discarded postpartum , in spite of its natural aging process , is still a rich source of stem cells capable to proliferate and in vitro differentiate in many directions . 0 ###LEFT-WALL### 3 placenta 0 ###LEFT-WALL### 30 and 0 ###LEFT-WALL### 37 . 2 human 3 placenta 3 placenta 5 which 3 placenta 11 in 3 placenta 19 is 4 , 5 which 5 which 6 is 5 which 10 , 6 is 8 discarded 7 routinely 8 discarded 8 discarded 9 postpartum 10 , 11 in 11 in 12 spite 11 in 18 , 12 spite 13 of 13 of 15 natural 14 its 15 natural 15 natural 16 aging 16 aging 17 process 19 is 20 still 20 still 23 source 21 a 22 rich 21 a 23 source 22 rich 23 source 23 source 24 of 24 of 26 cells 25 stem 26 cells 26 cells 27 capable 27 capable 28 to 28 to 30 and 29 proliferate 30 and 30 and 33 differentiate 30 and 34 in 31 in 32 vitro 32 vitro 33 differentiate 34 in 36 directions 35 many 36 directions besides homing and differentiation in the area of injury , mscs there elicit strong paracrine effects stimulating the processes of repair . 0 ###LEFT-WALL### 11 mscs 0 ###LEFT-WALL### 13 elicit 0 ###LEFT-WALL### 22 . 1 besides 3 and 1 besides 10 , 1 besides 11 mscs 2 homing 3 and 3 and 4 differentiation 3 and 5 in 5 in 7 area 6 the 7 area 7 area 8 of 8 of 9 injury 11 mscs 12 there 11 mscs 13 elicit 13 elicit 16 effects 14 strong 16 effects 15 paracrine 16 effects 16 effects 17 stimulating 17 stimulating 19 processes 18 the 19 processes 19 processes 20 of 20 of 21 repair in this review , we focus on the biology , characteristics and potential clinical applications of cells derived from human fetal membranes : amnion and chorion . 0 ###LEFT-WALL### 5 we 0 ###LEFT-WALL### 6 focus 0 ###LEFT-WALL### 23 : 0 ###LEFT-WALL### 27 . 1 in 3 review 1 in 4 , 1 in 5 we 2 this 3 review 5 we 6 focus 6 focus 7 on 6 focus 19 from 7 on 12 and 8 the 9 biology 9 biology 10 , 10 , 11 characteristics 10 , 12 and 12 and 15 applications 12 and 16 of 13 potential 15 applications 14 clinical 15 applications 16 of 17 cells 17 cells 18 derived 19 from 22 membranes 20 human 22 membranes 21 fetal 22 membranes 23 : 25 and 24 amnion 25 and 25 and 26 chorion purpose : endosonographic elastography has been introduced as a method of estimating the stiffness of pancreatic tumors . 0 ###LEFT-WALL### 1 purpose 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 18 . 1 purpose 2 : 2 : 3 endosonographic 3 endosonographic 4 elastography 3 endosonographic 12 estimating 4 elastography 5 has 5 has 6 been 6 been 7 introduced 7 introduced 8 as 8 as 10 method 9 a 10 method 10 method 11 of 11 of 12 estimating 12 estimating 14 stiffness 13 the 14 stiffness 14 stiffness 15 of 15 of 17 tumors 16 pancreatic 17 tumors this prospective single - center study was conducted to evaluate changes in the stiffness of the pancreas related to age and diffuse chronic pancreatitis . 0 ###LEFT-WALL### 6 study 0 ###LEFT-WALL### 21 and 0 ###LEFT-WALL### 25 . 1 this 6 study 2 prospective 5 center 3 single 4 - 3 single 5 center 5 center 6 study 6 study 7 was 7 was 21 and 8 conducted 9 to 8 conducted 12 in 8 conducted 19 to 8 conducted 21 and 9 to 10 evaluate 10 evaluate 11 changes 12 in 14 stiffness 13 the 14 stiffness 14 stiffness 15 of 14 stiffness 18 related 15 of 17 pancreas 16 the 17 pancreas 19 to 20 age 21 and 22 diffuse 22 diffuse 24 pancreatitis 23 chronic 24 pancreatitis patients and methods : 46 individuals each up to age 60 ( group 1 ) and over age 60 ( group 2 ) with healthy pancreata and 26 patients with diffuse chronic pancreatitis ( group 3 ) were included . 0 ###LEFT-WALL### 3 methods 0 ###LEFT-WALL### 4 : 0 ###LEFT-WALL### 27 and 0 ###LEFT-WALL### 40 . 1 patients 2 and 2 and 3 methods 3 methods 4 : 4 : 6 individuals 4 : 7 each 4 : 8 up 4 : 16 and 4 : 24 with 5 46 6 individuals 9 to 10 age 9 to 16 and 10 age 11 60 10 age 13 group 12 ( 13 group 13 group 14 1 13 group 15 ) 16 and 17 over 17 over 18 age 18 age 19 60 18 age 21 group 20 ( 21 group 21 group 22 2 21 group 23 ) 24 with 26 pancreata 25 healthy 26 pancreata 27 and 29 patients 27 and 39 included 28 26 29 patients 29 patients 30 with 29 patients 38 were 30 with 33 pancreatitis 31 diffuse 33 pancreatitis 32 chronic 33 pancreatitis 33 pancreatitis 35 group 34 ( 35 group 35 group 36 3 35 group 37 ) 38 were 39 included three elastograms were obtained in each case by endosonography in a defined section through the pancreatic body . 0 ###LEFT-WALL### 2 elastograms 0 ###LEFT-WALL### 4 obtained 0 ###LEFT-WALL### 18 . 1 three 2 elastograms 2 elastograms 3 were 3 were 4 obtained 4 obtained 5 in 4 obtained 8 by 4 obtained 10 in 4 obtained 14 through 5 in 7 case 6 each 7 case 8 by 9 endosonography 10 in 13 section 11 a 13 section 12 defined 13 section 14 through 17 body 15 the 17 body 16 pancreatic 17 body elastograms were further evaluated by histogram analysis . 0 ###LEFT-WALL### 1 elastograms 0 ###LEFT-WALL### 4 evaluated 0 ###LEFT-WALL### 8 . 1 elastograms 2 were 2 were 4 evaluated 3 further 4 evaluated 4 evaluated 5 by 5 by 7 analysis 6 histogram 7 analysis mean strain values , based on a range from 0 ( [hardest] [ )(to 255 [(] [softest] ) , and their standard deviation were calculated from the histogram . 0 ###LEFT-WALL### 1 mean 0 ###LEFT-WALL### 20 and 0 ###LEFT-WALL### 29 . 1 mean 3 values 1 mean 5 based 2 strain 3 values 4 , 5 based 5 based 6 on 5 based 19 , 6 on 8 range 7 a 8 range 8 range 9 from 9 from 10 0 10 0 14 )(to 11 ( 14 )(to 14 )(to 15 255 14 )(to 18 ) 19 , 20 and 20 and 23 deviation 20 and 25 calculated 21 their 23 deviation 22 standard 23 deviation 23 deviation 24 were 24 were 25 calculated 25 calculated 26 from 26 from 28 histogram 27 the 28 histogram the three groups were compared statistically with regard to pancreatic stiffness . 0 ###LEFT-WALL### 3 groups 0 ###LEFT-WALL### 5 compared 0 ###LEFT-WALL### 12 . 1 the 2 three 2 three 3 groups 3 groups 4 were 4 were 5 compared 5 compared 6 statistically 5 compared 7 with 5 compared 9 to 7 with 8 regard 9 to 11 stiffness 10 pancreatic 11 stiffness a cut [-] off level for the diagnosis of chronic pancreatitis was defined by testing receiver operating characteristics curves . 0 ###LEFT-WALL### 2 cut 0 ###LEFT-WALL### 13 defined 0 ###LEFT-WALL### 20 . 1 a 2 cut 2 cut 4 off 2 cut 6 for 2 cut 12 was 4 off 5 level 6 for 8 diagnosis 7 the 8 diagnosis 8 diagnosis 9 of 9 of 11 pancreatitis 10 chronic 11 pancreatitis 12 was 13 defined 13 defined 14 by 14 by 15 testing 15 testing 19 curves 16 receiver 17 operating 17 operating 18 characteristics 18 characteristics 19 curves results : the strain values ( mean , sd ) measured in the pancreatic body in groups 1 - 3 were 110.2 ( 23.9 ) , 80.0 ( 16.4 ) , [and] 32.4 ( 11.9 ) , respectively . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 19 - 0 ###LEFT-WALL### 39 . 1 results 2 : 2 : 4 strain 3 the 4 strain 4 strain 5 values 4 strain 11 measured 5 values 9 sd 5 values 11 measured 6 ( 9 sd 7 mean 8 , 7 mean 9 sd 9 sd 10 ) 11 measured 12 in 11 measured 16 in 12 in 15 body 13 the 15 body 14 pancreatic 15 body 16 in 17 groups 17 groups 18 1 19 - 20 3 19 - 21 were 20 3 21 were 21 were 22 110.2 21 were 38 respectively 22 110.2 24 23.9 22 110.2 27 80.0 23 ( 24 23.9 24 23.9 25 ) 26 , 27 80.0 27 80.0 29 16.4 27 80.0 33 32.4 27 80.0 37 , 28 ( 29 16.4 29 16.4 30 ) 31 , 33 32.4 33 32.4 35 11.9 33 32.4 36 ) 34 ( 35 11.9 35 11.9 36 ) pairwise comparison of the groups revealed highly significant differences ( p < 0.001 ) . 0 ###LEFT-WALL### 2 comparison 0 ###LEFT-WALL### 6 revealed 0 ###LEFT-WALL### 15 . 1 pairwise 2 comparison 2 comparison 3 of 2 comparison 6 revealed 3 of 5 groups 4 the 5 groups 6 revealed 9 differences 7 highly 8 significant 8 significant 9 differences 9 differences 12 < 10 ( 12 < 11 p 12 < 12 < 13 0.001 12 < 14 ) at a cut - off value of 50 , the area under the curve was 0.993 for distinguishing between chronic pancreatitis and healthy pancreata in people aged over 60 . 0 ###LEFT-WALL### 11 area 0 ###LEFT-WALL### 15 was 0 ###LEFT-WALL### 30 . 1 at 3 cut 1 at 9 , 1 at 11 area 2 a 3 cut 3 cut 5 off 4 - 5 off 5 off 6 value 5 off 9 , 6 value 7 of 7 of 8 50 10 the 11 area 11 area 12 under 11 area 15 was 12 under 14 curve 13 the 14 curve 15 was 16 0.993 16 0.993 17 for 16 0.993 19 between 17 for 18 distinguishing 19 between 24 pancreata 20 chronic 21 pancreatitis 21 pancreatitis 22 and 22 and 23 healthy 22 and 24 pancreata 24 pancreata 25 in 24 pancreata 27 aged 24 pancreata 28 over 25 in 26 people 28 over 29 60 conclusion : semiquantitative elastography shows that pancreata become significantly harder during aging , but remain softer than in chronic pancreatitis . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 5 shows 2 : 14 but 2 : 21 . 3 semiquantitative 5 shows 4 elastography 5 shows 5 shows 6 that 5 shows 7 pancreata 5 shows 14 but 6 that 7 pancreata 8 become 9 significantly 8 become 10 harder 8 become 14 but 10 harder 11 during 11 during 12 aging 13 , 14 but 14 but 15 remain 15 remain 16 softer 16 softer 17 than 17 than 18 in 18 in 20 pancreatitis 19 chronic 20 pancreatitis a cut [-] off value of 50 is suggested as a possible diagnostic criterion for diffuse chronic pancreatitis . 0 ###LEFT-WALL### 2 cut 0 ###LEFT-WALL### 9 suggested 0 ###LEFT-WALL### 19 . 1 a 2 cut 2 cut 4 off 2 cut 6 of 2 cut 8 is 4 off 5 value 6 of 7 50 8 is 9 suggested 9 suggested 10 as 10 as 14 criterion 11 a 12 possible 11 a 14 criterion 12 possible 13 diagnostic 13 diagnostic 14 criterion 14 criterion 15 for 15 for 18 pancreatitis 16 diffuse 18 pancreatitis 17 chronic 18 pancreatitis eyelid blepharoplasty is a common plastic surgical procedure in patients between the age of 40 and 60 and is performed by different specialists . 0 ###LEFT-WALL### 2 blepharoplasty 0 ###LEFT-WALL### 18 and 0 ###LEFT-WALL### 24 . 1 eyelid 2 blepharoplasty 2 blepharoplasty 18 and 3 is 8 procedure 3 is 18 and 4 a 5 common 4 a 8 procedure 5 common 8 procedure 6 plastic 8 procedure 7 surgical 8 procedure 8 procedure 9 in 9 in 10 patients 10 patients 11 between 11 between 13 age 12 the 13 age 13 age 14 of 14 of 16 and 15 40 16 and 16 and 17 60 18 and 19 is 19 is 20 performed 20 performed 21 by 21 by 23 specialists 22 different 23 specialists preoperative [evaluation] and understanding the patient 's aesthetic expectations are essential for surgery planning . 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 15 . 1 preoperative 3 and 3 and 4 understanding 3 and 9 expectations 3 and 14 planning 5 the 6 patient 6 patient 7 's 7 's 9 expectations 8 aesthetic 9 expectations 9 expectations 10 are 10 are 11 essential 11 essential 12 for 12 for 13 surgery 13 surgery 14 planning laser blepharoplasty offers the possibility to perform incision [and] haemostasis with the same device . 0 ###LEFT-WALL### 2 blepharoplasty 0 ###LEFT-WALL### 3 offers 0 ###LEFT-WALL### 15 . 1 laser 2 blepharoplasty 2 blepharoplasty 3 offers 3 offers 5 possibility 3 offers 6 to 4 the 5 possibility 6 to 7 perform 7 perform 10 haemostasis 7 perform 11 with 8 incision 10 haemostasis 11 with 14 device 12 the 13 same 13 same 14 device this article reports on our experience with the co2 laser . 0 ###LEFT-WALL### 2 article 0 ###LEFT-WALL### 3 reports 0 ###LEFT-WALL### 11 . 1 this 2 article 2 article 3 reports 3 reports 4 on 3 reports 7 with 4 on 6 experience 5 our 6 experience 7 with 10 laser 8 the 10 laser 9 co2 10 laser as the average lifespan of humans continues to increase , improvement in the quality of life for elderly people is important . 0 ###LEFT-WALL### 11 improvement 0 ###LEFT-WALL### 20 is 0 ###LEFT-WALL### 22 . 1 as 4 lifespan 1 as 7 continues 1 as 10 , 1 as 11 improvement 2 the 4 lifespan 3 average 4 lifespan 4 lifespan 5 of 4 lifespan 7 continues 5 of 6 humans 7 continues 8 to 7 continues 9 increase 8 to 9 increase 11 improvement 12 in 11 improvement 20 is 12 in 14 quality 13 the 14 quality 14 quality 15 of 15 of 16 life 16 life 17 for 17 for 19 people 18 elderly 19 people 20 is 21 important among the most severe problems during aging are bone loss - associated diseases such as poor fracture healing and osteoporosis . 0 ###LEFT-WALL### 5 problems 0 ###LEFT-WALL### 9 bone 0 ###LEFT-WALL### 11 - 1 among 3 most 1 among 5 problems 2 the 3 most 4 severe 5 problems 5 problems 6 during 5 problems 8 are 6 during 7 aging 8 are 9 bone 9 bone 10 loss 11 - 19 and 11 - 21 . 12 associated 13 diseases 13 diseases 15 as 13 diseases 19 and 14 such 15 as 15 as 18 healing 16 poor 17 fracture 17 fracture 18 healing 19 and 20 osteoporosis therapy - induced bone loss such as bisphosphonate - associated osteonecrosis of the jaw also increases in incidence [with] age . 0 ###LEFT-WALL### 5 loss 0 ###LEFT-WALL### 16 increases 0 ###LEFT-WALL### 21 . 1 therapy 2 - 1 therapy 5 loss 3 induced 4 bone 4 bone 5 loss 5 loss 7 as 5 loss 16 increases 6 such 7 as 7 as 11 osteonecrosis 8 bisphosphonate 9 - 8 bisphosphonate 11 osteonecrosis 10 associated 11 osteonecrosis 11 osteonecrosis 12 of 12 of 14 jaw 13 the 14 jaw 15 also 16 increases 16 increases 17 in 17 in 20 age 18 incidence 20 age most of the current treatment strategies are focused on antiresorptive and bone formation pharmacological agents , but it is hard to obtain appropriate bone augmentation and there are concerns regarding their long - term safety without side effects . 0 ###LEFT-WALL### 6 strategies 0 ###LEFT-WALL### 17 but 0 ###LEFT-WALL### 26 and 0 ###LEFT-WALL### 39 . 1 most 2 of 1 most 6 strategies 2 of 6 strategies 3 the 6 strategies 4 current 5 treatment 5 treatment 6 strategies 6 strategies 7 are 7 are 17 but 8 focused 9 on 8 focused 17 but 9 on 11 and 10 antiresorptive 11 and 11 and 15 agents 11 and 16 , 12 bone 15 agents 13 formation 15 agents 14 pharmacological 15 agents 17 but 22 obtain 18 it 19 is 19 is 20 hard 20 hard 21 to 21 to 22 obtain 22 obtain 25 augmentation 23 appropriate 25 augmentation 24 bone 25 augmentation 26 and 27 there 26 and 28 are 27 there 28 are 28 are 29 concerns 29 concerns 30 regarding 30 regarding 35 safety 31 their 35 safety 32 long 33 - 32 long 34 term 34 term 35 safety 35 safety 36 without 36 without 38 effects 37 side 38 effects therefore , a novel method for improvement of bone quality is required , and stem cells are of great interest as potential therapeutic tools for diseases that remain without clinically effective therapies . 0 ###LEFT-WALL### 5 method 0 ###LEFT-WALL### 12 required 0 ###LEFT-WALL### 14 and 0 ###LEFT-WALL### 33 . 1 therefore 2 , 1 therefore 5 method 3 a 4 novel 3 a 5 method 4 novel 5 method 5 method 6 for 5 method 11 is 6 for 7 improvement 7 improvement 8 of 8 of 10 quality 9 bone 10 quality 11 is 12 required 13 , 14 and 14 and 16 cells 14 and 17 are 15 stem 16 cells 16 cells 17 are 17 are 18 of 17 are 21 as 18 of 20 interest 19 great 20 interest 21 as 24 tools 22 potential 24 tools 23 therapeutic 24 tools 24 tools 25 for 24 tools 27 that 24 tools 28 remain 25 for 26 diseases 27 that 28 remain 28 remain 29 without 29 without 32 therapies 30 clinically 31 effective 31 effective 32 therapies in this review , we describe the concept of stem cell [-] based therapy and evaluate the current progress of cell therapy for the improvement of bone quality . 0 ###LEFT-WALL### 5 we 0 ###LEFT-WALL### 15 and 0 ###LEFT-WALL### 29 . 1 in 3 review 1 in 4 , 1 in 5 we 2 this 3 review 5 we 15 and 6 describe 8 concept 6 describe 15 and 7 the 8 concept 8 concept 9 of 9 of 14 therapy 10 stem 13 based 11 cell 13 based 13 based 14 therapy 15 and 16 evaluate 16 evaluate 19 progress 17 the 19 progress 18 current 19 progress 19 progress 20 of 20 of 22 therapy 21 cell 22 therapy 22 therapy 23 for 22 therapy 26 of 23 for 25 improvement 24 the 25 improvement 26 of 28 quality 27 bone 28 quality in addition , we report and discuss a new clinical strategy in which improved bone quality was obtained by applying bone [-] marrow derived mscs with platelet rich plasma in clinical therapy . 0 ###LEFT-WALL### 4 we 0 ###LEFT-WALL### 33 . 1 in 2 addition 1 in 3 , 1 in 4 we 4 we 6 and 5 report 6 and 6 and 7 discuss 6 and 11 strategy 8 a 11 strategy 9 new 11 strategy 10 clinical 11 strategy 11 strategy 12 in 12 in 13 which 12 in 15 bone 12 in 16 quality 12 in 18 obtained 13 which 15 bone 14 improved 15 bone 16 quality 17 was 17 was 18 obtained 18 obtained 19 by 19 by 20 applying 20 applying 25 mscs 20 applying 26 with 21 bone 23 marrow 23 marrow 24 derived 24 derived 25 mscs 26 with 29 plasma 27 platelet 29 plasma 28 rich 29 plasma 29 plasma 30 in 30 in 32 therapy 31 clinical 32 therapy unlabelled : the purpose of this study was to identify whether young adult bone structural strength at the hip is associated with adolescent lean tissue [mass] ( ltm ) accrual . 0 ###LEFT-WALL### 1 unlabelled 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 31 . 1 unlabelled 2 : 2 : 4 purpose 3 the 4 purpose 4 purpose 5 of 4 purpose 7 study 4 purpose 10 identify 5 of 6 this 7 study 8 was 8 was 9 to 8 was 10 identify 9 to 10 identify 10 identify 11 whether 10 identify 22 with 11 whether 16 strength 11 whether 21 associated 12 young 13 adult 13 adult 14 bone 14 bone 16 strength 15 structural 16 strength 16 strength 17 at 16 strength 20 is 17 at 19 hip 18 the 19 hip 20 is 21 associated 22 with 25 tissue 22 with 30 accrual 23 adolescent 25 tissue 24 lean 25 tissue 25 tissue 28 ltm 27 ( 28 ltm 28 ltm 29 ) it was observed that those individuals who accrued more ltm from adolescence to adulthood had significantly greater adult bone structural strength at the hip . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 3 observed 0 ###LEFT-WALL### 25 . 1 it 2 was 2 was 3 observed 3 observed 4 that 4 that 6 individuals 4 that 15 had 5 those 6 individuals 6 individuals 7 who 6 individuals 8 accrued 6 individuals 15 had 7 who 8 accrued 8 accrued 10 ltm 8 accrued 11 from 8 accrued 13 to 9 more 10 ltm 11 from 12 adolescence 13 to 14 adulthood 15 had 21 strength 15 had 22 at 16 significantly 17 greater 17 greater 18 adult 18 adult 21 strength 19 bone 21 strength 20 structural 21 strength 22 at 24 hip 23 the 24 hip introduction : the purpose of this study [was] to identify whether young adult bone cross [-] sectional area ( csa ) , section modulus ( z ) , and outer diameter [(] [od] ) at the hip were associated with adolescent ltm accrual . 0 ###LEFT-WALL### 1 introduction 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 44 . 2 : 29 and 2 : 39 associated 3 the 4 purpose 4 purpose 5 of 4 purpose 29 and 5 of 7 study 6 this 7 study 7 study 9 to 7 study 22 , 9 to 22 , 10 identify 11 whether 10 identify 18 area 10 identify 22 , 11 whether 12 young 13 adult 15 cross 14 bone 15 cross 15 cross 18 area 17 sectional 18 area 18 area 20 csa 19 ( 20 csa 20 csa 21 ) 22 , 23 section 23 section 24 modulus 24 modulus 26 z 25 ( 26 z 26 z 27 ) 28 , 29 and 29 and 31 diameter 29 and 34 ) 29 and 35 at 29 and 38 were 30 outer 31 diameter 35 at 37 hip 36 the 37 hip 38 were 39 associated 39 associated 40 with 39 associated 43 accrual 40 with 42 ltm 41 adolescent 42 ltm methods : one hundred three young adult participants ( 55 males , 48 females ) were tertiled into adolescent ltm accrual groupings . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 23 . 2 : 8 participants 2 : 17 tertiled 3 one 4 hundred 4 hundred 5 three 5 three 8 participants 6 young 8 participants 7 adult 8 participants 8 participants 11 males 8 participants 16 were 9 ( 11 males 10 55 11 males 11 males 14 females 11 males 15 ) 12 , 14 females 13 48 14 females 14 females 15 ) 16 were 17 tertiled 17 tertiled 18 into 18 into 22 groupings 19 adolescent 22 groupings 20 ltm 22 groupings 21 accrual 22 groupings ltm [accrual] was assessed by serial measures using dual energy x - ray absorptiometry ( dxa ) from adolescence to young adulthood ( 21.3 ± 1.3 years ) . 0 ###LEFT-WALL### 1 ltm 0 ###LEFT-WALL### 4 assessed 0 ###LEFT-WALL### 12 - 0 ###LEFT-WALL### 29 . 1 ltm 3 was 3 was 4 assessed 4 assessed 5 by 4 assessed 8 using 5 by 7 measures 6 serial 7 measures 8 using 10 energy 9 dual 10 energy 10 energy 11 x 12 - 13 ray 13 ray 14 absorptiometry 13 ray 18 from 13 ray 20 to 14 absorptiometry 16 dxa 15 ( 16 dxa 16 dxa 17 ) 18 from 19 adolescence 20 to 22 adulthood 21 young 22 adulthood 22 adulthood 27 years 23 ( 27 years 24 21.3 27 years 25 ± 27 years 26 1.3 27 years 27 years 28 ) csa , z , and [od] [at] the narrow neck ( nn ) and femoral shaft ( s ) sites of the proximal femur were assessed in young adulthood ( 21.3 ± 4.5 years ) , using hip structural analysis . 0 ###LEFT-WALL### 20 sites 0 ###LEFT-WALL### 26 assessed 1 csa 2 , 2 , 3 z 2 , 5 and 4 , 5 and 5 and 10 neck 5 and 12 nn 5 and 14 and 8 the 10 neck 9 narrow 10 neck 11 ( 12 nn 12 nn 13 ) 14 and 16 shaft 14 and 18 s 14 and 20 sites 15 femoral 16 shaft 17 ( 18 s 18 s 19 ) 20 sites 21 of 20 sites 25 were 21 of 24 femur 22 the 24 femur 23 proximal 24 femur 25 were 26 assessed 26 assessed 27 in 27 in 29 adulthood 28 young 29 adulthood 29 adulthood 34 years 29 adulthood 37 using 30 ( 34 years 31 21.3 34 years 32 ± 34 years 33 4.5 34 years 34 years 35 ) 36 , 37 using 37 using 40 analysis 37 using 41 . 38 hip 40 analysis 39 structural 40 analysis group differences were assessed using an analysis of covariance , controlling for adult height , weight , sex , and physical activity levels . 0 ###LEFT-WALL### 2 differences 0 ###LEFT-WALL### 4 assessed 0 ###LEFT-WALL### 20 and 0 ###LEFT-WALL### 24 . 1 group 2 differences 2 differences 3 were 3 were 4 assessed 4 assessed 5 using 5 using 7 analysis 6 an 7 analysis 7 analysis 8 of 8 of 9 covariance 9 covariance 11 controlling 10 , 11 controlling 11 controlling 12 for 11 controlling 18 sex 11 controlling 19 , 12 for 14 height 13 adult 14 height 14 height 16 weight 15 , 16 weight 16 weight 17 , 19 , 20 and 20 and 22 activity 20 and 23 levels 21 physical 22 activity 22 activity 23 levels conclusions : these findings suggest that the amount of ltm accrued from adolescence to young adulthood has a positive influence on adult bone structural strength at the proximal femur . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 4 findings 2 : 5 suggest 2 : 30 . 3 these 4 findings 4 findings 5 suggest 5 suggest 6 that 5 suggest 17 has 6 that 8 amount 6 that 11 accrued 6 that 17 has 7 the 8 amount 8 amount 9 of 8 amount 11 accrued 9 of 10 ltm 11 accrued 12 from 11 accrued 14 to 12 from 13 adolescence 14 to 16 adulthood 15 young 16 adulthood 17 has 20 influence 17 has 21 on 17 has 26 at 18 a 19 positive 18 a 20 influence 19 positive 20 influence 21 on 25 strength 22 adult 23 bone 23 bone 25 strength 24 structural 25 strength 26 at 29 femur 27 the 29 femur 28 proximal 29 femur astaxanthin [(] [ast] ) is a carotenoid pigment which possesses potent antioxidative , anti - inflammatory , and neuroprotective properties . 0 ###LEFT-WALL### 1 astaxanthin 0 ###LEFT-WALL### 5 is 0 ###LEFT-WALL### 21 . 1 astaxanthin 4 ) 1 astaxanthin 5 is 5 is 7 carotenoid 5 is 8 pigment 6 a 7 carotenoid 8 pigment 9 which 8 pigment 10 possesses 9 which 10 possesses 10 possesses 20 properties 11 potent 20 properties 12 antioxidative 13 , 12 antioxidative 20 properties 14 anti 15 - 14 anti 20 properties 16 inflammatory 18 and 17 , 18 and 18 and 19 neuroprotective 18 and 20 properties the aim of this study was to investigate whether administration of [ast] [had] protective effects on d - galactose - induced brain aging in rats , and further examined its protective mechanisms . 0 ###LEFT-WALL### 2 aim 0 ###LEFT-WALL### 27 and 0 ###LEFT-WALL### 33 . 1 the 2 aim 2 aim 3 of 2 aim 27 and 3 of 5 study 4 this 5 study 6 was 7 to 6 was 8 investigate 6 was 27 and 7 to 8 investigate 8 investigate 9 whether 9 whether 10 administration 9 whether 21 induced 10 administration 11 of 10 administration 21 induced 11 of 15 effects 14 protective 15 effects 15 effects 16 on 15 effects 19 galactose 16 on 17 d 18 - 19 galactose 19 galactose 20 - 21 induced 22 brain 21 induced 24 in 22 brain 23 aging 24 in 25 rats 26 , 27 and 27 and 29 examined 27 and 32 mechanisms 28 further 29 examined 30 its 32 mechanisms 31 protective 32 mechanisms the results showed that [ast] treatment significantly restored the activities of glutathione peroxidase ( gsh - px [ )(and superoxide dismutase ( sod ) , and increased glutathione [(] gsh [ )(contents and total antioxidant capacity ( t - aoc ) , but decreased malondialdehyde ( mda ) , protein carbonylation [and] 8 - hydroxy - 2 - deoxyguanosine ( 8 - ohdg [ )(levels in the brains of aging rats . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 showed 1 the 2 results 2 results 3 showed 3 showed 6 treatment 3 showed 8 restored 4 that 6 treatment 6 treatment 8 restored 7 significantly 8 restored 8 restored 10 activities 8 restored 16 - 9 the 10 activities 10 activities 11 of 11 of 13 peroxidase 12 glutathione 13 peroxidase 14 ( 16 - 15 gsh 16 - 16 - 26 and 17 px 19 )(and 19 )(and 21 dismutase 19 )(and 23 sod 19 )(and 26 and 20 superoxide 21 dismutase 22 ( 23 sod 23 sod 24 ) 25 , 26 and 26 and 28 glutathione 26 and 30 gsh 26 and 33 and 27 increased 28 glutathione 30 gsh 33 and 32 )(contents 33 and 33 and 43 but 34 total 36 capacity 34 total 43 but 35 antioxidant 36 capacity 36 capacity 38 t 36 capacity 40 aoc 37 ( 38 t 38 t 39 - 39 - 40 aoc 40 aoc 41 ) 42 , 43 but 43 but 44 decreased 44 decreased 51 carbonylation 45 malondialdehyde 47 mda 45 malondialdehyde 49 , 45 malondialdehyde 50 protein 46 ( 47 mda 47 mda 48 ) 50 protein 51 carbonylation 51 carbonylation 53 8 51 carbonylation 55 hydroxy 51 carbonylation 58 - 51 carbonylation 62 - 54 - 55 hydroxy 55 hydroxy 56 - 56 - 58 - 57 2 58 - 58 - 59 deoxyguanosine 60 ( 62 - 61 8 62 - 62 - 65 )(levels 62 - 72 . 63 ohdg 65 )(levels 65 )(levels 66 in 65 )(levels 69 of 66 in 68 brains 67 the 68 brains 69 of 70 aging 70 aging 71 rats furthermore , [ast] increased the ratio of bcl - 2/bax , but decreased the expression of cyclooxygenase - 2 ( cox - 2 ) in the brains of aging rats . 0 ###LEFT-WALL### 12 but 0 ###LEFT-WALL### 31 . 1 furthermore 2 , 1 furthermore 12 but 4 increased 6 ratio 4 increased 12 but 5 the 6 ratio 6 ratio 7 of 7 of 8 bcl 8 bcl 10 2/bax 9 - 10 2/bax 10 2/bax 11 , 12 but 13 decreased 13 decreased 15 expression 13 decreased 25 in 14 the 15 expression 15 expression 16 of 16 of 17 cyclooxygenase 17 cyclooxygenase 19 2 18 - 19 2 19 2 21 cox 19 2 24 ) 20 ( 21 cox 21 cox 23 2 21 cox 24 ) 22 - 23 2 23 2 24 ) 25 in 27 brains 26 the 27 brains 27 brains 28 of 28 of 29 aging 29 aging 30 rats additionally , [ast] ameliorated histopathological changes in the hippocampus and restored brain derived neurotrophic [factor] ( bdnf ) levels in both the brains and hippocampus of aging rats . 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 13 derived 0 ###LEFT-WALL### 29 . 1 additionally 2 , 1 additionally 10 and 4 ameliorated 6 changes 5 histopathological 6 changes 6 changes 7 in 6 changes 10 and 7 in 9 hippocampus 8 the 9 hippocampus 10 and 12 brain 10 and 13 derived 11 restored 12 brain 13 derived 19 levels 14 neurotrophic 17 bdnf 14 neurotrophic 19 levels 16 ( 17 bdnf 17 bdnf 18 ) 19 levels 20 in 19 levels 26 of 20 in 24 and 21 both 24 and 22 the 23 brains 23 brains 24 and 24 and 25 hippocampus 26 of 27 aging 27 aging 28 rats these results suggested that [ast] could alleviate brain aging , which may be due to attenuating oxidative stress , ameliorating hippocampus damage , and upregulating bdnf expression . 1 these 2 results 2 results 3 suggested 3 suggested 4 that 3 suggested 7 alleviate 4 that 6 could 6 could 7 alleviate 7 alleviate 8 brain 7 alleviate 20 ameliorating 8 brain 9 aging 8 brain 11 which 10 , 11 which 11 which 12 may 11 which 19 , 12 may 13 be 13 be 14 due 14 due 15 to 15 to 16 attenuating 16 attenuating 18 stress 17 oxidative 18 stress 19 , 20 ameliorating 20 ameliorating 24 and 20 ameliorating 28 . 21 hippocampus 22 damage 22 damage 24 and 23 , 24 and 24 and 27 expression 25 upregulating 27 expression 26 bdnf 27 expression background : proximal humeral fractures are mainly associated with osteoporosis and [are] becoming more common with the aging of our society . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 22 . 2 : 5 fractures 2 : 8 associated 3 proximal 5 fractures 4 humeral 5 fractures 5 fractures 6 are 6 are 8 associated 7 mainly 8 associated 8 associated 9 with 8 associated 15 common 9 with 11 and 10 osteoporosis 11 and 11 and 13 becoming 14 more 15 common 15 common 16 with 16 with 18 aging 17 the 18 aging 18 aging 19 of 19 of 21 society 20 our 21 society the best surgical approach for internal fixation of displaced proximal humeral fractures is still being debated . 0 ###LEFT-WALL### 4 approach 0 ###LEFT-WALL### 13 is 0 ###LEFT-WALL### 17 . 1 the 2 best 1 the 4 approach 3 surgical 4 approach 4 approach 5 for 4 approach 13 is 5 for 7 fixation 6 internal 7 fixation 7 fixation 8 of 8 of 12 fractures 9 displaced 12 fractures 10 proximal 12 fractures 11 humeral 12 fractures 13 is 15 being 14 still 15 being 15 being 16 debated questions/purposes : in this prospective randomized study , we aimed to investigate whether the deltoid - split approach is superior to the deltopectoral approach with regard [to] ( 1 ) complication rate [;] [(] 2 [ )(shoulder function ( constant [score] ) [;] and [(] [3] [ )(pain [(] visual analog scale [ vas []] [ )( internal fixation of displaced humeral fractures with a polyaxial locking plate . 0 ###LEFT-WALL### 1 questions/purposes 0 ###LEFT-WALL### 8 , 0 ###LEFT-WALL### 12 investigate 1 questions/purposes 2 : 2 : 3 in 3 in 7 study 4 this 5 prospective 5 prospective 7 study 6 randomized 7 study 8 , 9 we 9 we 10 aimed 10 aimed 11 to 11 to 12 investigate 12 investigate 13 whether 13 whether 18 approach 13 whether 19 is 14 the 18 approach 15 deltoid 16 - 15 deltoid 18 approach 17 split 18 approach 18 approach 19 is 19 is 20 superior 19 is 25 with 20 superior 21 to 21 to 24 approach 22 the 24 approach 23 deltopectoral 24 approach 25 with 26 regard 25 with 32 rate 26 regard 29 1 28 ( 29 1 29 1 30 ) 31 complication 32 rate 32 rate 35 2 32 rate 44 and 35 2 44 and 37 )(shoulder 38 function 37 )(shoulder 44 and 38 function 40 constant 39 ( 40 constant 40 constant 42 ) 44 and 48 )(pain 48 )(pain 52 scale 50 visual 52 scale 51 analog 52 scale 52 scale 59 fixation 53 [ 59 fixation 54 vas 59 fixation 58 internal 59 fixation 59 fixation 60 of 59 fixation 69 . 60 of 63 fractures 61 displaced 63 fractures 62 humeral 63 fractures 63 fractures 64 with 64 with 68 plate 65 a 68 plate 66 polyaxial 68 plate 67 locking 68 plate methods : we randomized 120 patients with proximal humeral fractures to receive one of these two approaches ( 60 patients for each approach ) . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 12 receive 0 ###LEFT-WALL### 25 . 2 : 3 we 2 : 4 randomized 3 we 4 randomized 4 randomized 6 patients 4 randomized 7 with 4 randomized 11 to 5 120 6 patients 7 with 10 fractures 8 proximal 10 fractures 9 humeral 10 fractures 11 to 12 receive 12 receive 13 one 13 one 14 of 14 of 17 approaches 15 these 16 two 16 two 17 approaches 17 approaches 20 patients 18 ( 20 patients 19 60 20 patients 20 patients 21 for 20 patients 24 ) 21 for 23 approach 22 each 23 approach we prospectively documented demographic and perioperative data ( sex , age , fracture type , hospital stay , operation time , and fluoroscopy time ) as well as complications . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 documented 0 ###LEFT-WALL### 30 . 1 we 3 documented 2 prospectively 3 documented 3 documented 7 data 3 documented 28 as 4 demographic 5 and 5 and 6 perioperative 5 and 7 data 7 data 9 sex 7 data 22 and 8 ( 9 sex 9 sex 10 , 10 , 22 and 11 age 12 , 12 , 14 type 12 , 15 , 13 fracture 14 type 15 , 17 stay 15 , 18 , 16 hospital 17 stay 18 , 20 time 18 , 22 and 19 operation 20 time 21 , 22 and 22 and 24 time 22 and 25 ) 23 fluoroscopy 24 time 26 as 27 well 27 well 28 as 28 as 29 complications followup examinations were conducted at 6 weeks , 6 months , and 12 months postoperatively , including radiological and clinical evaluations ( constant [score] , activities of daily living , and pain [ vas ] ) . 0 ###LEFT-WALL### 2 examinations 0 ###LEFT-WALL### 4 conducted 1 followup 2 examinations 2 examinations 3 were 3 were 4 conducted 4 conducted 5 at 4 conducted 15 postoperatively 4 conducted 17 including 5 at 12 and 6 6 7 weeks 7 weeks 10 months 7 weeks 12 and 8 , 10 months 9 6 10 months 10 months 11 , 11 , 12 and 12 and 14 months 13 12 14 months 16 , 17 including 17 including 19 and 17 including 21 evaluations 17 including 37 . 18 radiological 19 and 19 and 20 clinical 21 evaluations 23 constant 22 ( 23 constant 23 constant 31 and 23 constant 37 . 25 , 31 and 26 activities 27 of 26 activities 31 and 27 of 29 living 28 daily 29 living 30 , 31 and 31 and 32 pain 31 and 34 vas 31 and 36 ) 33 [ 34 vas 34 vas 35 ] baseline and perioperative data were comparable for both approaches . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 5 were 0 ###LEFT-WALL### 10 . 1 baseline 2 and 2 and 4 data 2 and 5 were 3 perioperative 4 data 5 were 6 comparable 6 comparable 7 for 7 for 9 approaches 8 both 9 approaches the sample size was chosen to provide 80 % power , but it reached only 68 % as a result of the loss of followups to detect a 10 [-] point difference on the constant score , which we considered the minimum clinically important difference . 0 ###LEFT-WALL### 3 size 0 ###LEFT-WALL### 5 chosen 0 ###LEFT-WALL### 12 but 1 the 3 size 2 sample 3 size 3 size 4 was 4 was 5 chosen 5 chosen 6 to 6 to 7 provide 7 provide 10 power 8 80 9 % 9 % 10 power 11 , 12 but 12 but 13 it 12 but 14 reached 13 it 14 reached 14 reached 17 % 14 reached 26 to 15 only 16 68 16 68 17 % 17 % 18 as 18 as 20 result 19 a 20 result 20 result 21 of 21 of 23 loss 22 the 23 loss 23 loss 24 of 24 of 25 followups 26 to 27 detect 27 detect 32 difference 27 detect 33 on 28 a 32 difference 29 10 31 point 31 point 32 difference 33 on 36 score 34 the 36 score 35 constant 36 score 36 score 38 which 37 , 38 which 38 which 40 considered 38 which 46 . 39 we 40 considered 40 considered 45 difference 41 the 45 difference 42 minimum 45 difference 43 clinically 44 important 44 important 45 difference results : complications or reoperations between the approaches were not different . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 4 or 2 : 9 were 2 : 12 . 3 complications 4 or 4 or 5 reoperations 4 or 6 between 4 or 9 were 6 between 8 approaches 7 the 8 approaches 9 were 10 not 9 were 11 different 10 not 11 different eight patients in the deltoid - split group ( 14 % ) needed surgical revisions compared with seven patients in the deltopectoral group ( 13 % [;] p = 1.00 ) . 0 ###LEFT-WALL### 1 eight 0 ###LEFT-WALL### 13 needed 0 ###LEFT-WALL### 32 . 1 eight 2 patients 1 eight 8 group 1 eight 11 % 1 eight 13 needed 2 patients 3 in 2 patients 8 group 3 in 7 split 4 the 7 split 5 deltoid 6 - 5 deltoid 7 split 9 ( 11 % 10 14 11 % 11 % 12 ) 13 needed 15 revisions 14 surgical 15 revisions 15 revisions 16 compared 16 compared 17 with 16 compared 20 in 17 with 19 patients 18 seven 19 patients 20 in 23 group 21 the 23 group 22 deltopectoral 23 group 23 group 26 % 24 ( 26 % 25 13 26 % 26 % 29 = 26 % 31 ) 28 p 29 = 29 = 30 1.00 29 = 31 ) no learning - curve effects were noted ; fluoroscopy use during surgery and function and pain scores during followups were similar among the first 30 patients and the next 30 patients treated in each group . 0 ###LEFT-WALL### 5 effects 0 ###LEFT-WALL### 7 noted 0 ###LEFT-WALL### 8 ; 0 ###LEFT-WALL### 35 group 0 ###LEFT-WALL### 36 . 1 no 5 effects 2 learning 3 - 2 learning 5 effects 4 curve 5 effects 5 effects 6 were 6 were 7 noted 8 ; 9 fluoroscopy 8 ; 20 were 9 fluoroscopy 20 were 10 use 11 during 10 use 15 and 11 during 13 and 12 surgery 13 and 13 and 14 function 15 and 17 scores 15 and 18 during 15 and 20 were 16 pain 17 scores 18 during 19 followups 20 were 21 similar 21 similar 22 among 22 among 25 30 23 the 24 first 23 the 25 30 25 30 27 and 25 30 35 group 26 patients 27 and 27 and 31 patients 27 and 32 treated 27 and 33 in 27 and 35 group 28 the 29 next 28 the 30 30 30 30 31 patients 33 in 34 each conclusions : the treatment of proximal humeral fractures with a polyaxial locking plate is reliable using both approaches . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 4 treatment 2 : 14 is 2 : 19 . 3 the 4 treatment 4 treatment 5 of 4 treatment 14 is 5 of 8 fractures 6 proximal 8 fractures 7 humeral 8 fractures 8 fractures 9 with 9 with 13 plate 10 a 11 polyaxial 10 a 13 plate 11 polyaxial 13 plate 12 locking 13 plate 14 is 15 reliable 15 reliable 16 using 16 using 18 approaches 17 both 18 approaches for a definitive recommendation for one of these approaches , further studies with appropriate sample size are necessary . 0 ###LEFT-WALL### 12 studies 0 ###LEFT-WALL### 17 are 0 ###LEFT-WALL### 19 . 1 for 4 recommendation 1 for 10 , 1 for 12 studies 2 a 3 definitive 2 a 4 recommendation 3 definitive 4 recommendation 4 recommendation 5 for 5 for 6 one 6 one 7 of 7 of 9 approaches 8 these 9 approaches 11 further 12 studies 12 studies 13 with 12 studies 17 are 13 with 16 size 14 appropriate 15 sample 15 sample 16 size 17 are 18 necessary level of evidence : level ii , therapeutic study . 0 ###LEFT-WALL### 3 evidence 0 ###LEFT-WALL### 4 : 0 ###LEFT-WALL### 7 , 0 ###LEFT-WALL### 10 . 1 level 2 of 2 of 3 evidence 3 evidence 4 : 4 : 5 level 5 level 6 ii 7 , 9 study 8 therapeutic 9 study see the guidelines for authors for a complete description of levels of evidence . 0 ###LEFT-WALL### 1 see 0 ###LEFT-WALL### 14 . 1 see 3 guidelines 2 the 3 guidelines 3 guidelines 4 for 4 for 5 authors 5 authors 6 for 6 for 9 description 7 a 8 complete 7 a 9 description 8 complete 9 description 9 description 10 of 10 of 11 levels 11 levels 12 of 12 of 13 evidence background : few studies of gene variants that affect estrogen activity investigate their association with age at onset [of] alzheimer 's disease ( ad ) in women of different ethnicities . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 4 studies 2 : 12 investigate 2 : 31 . 3 few 4 studies 4 studies 5 of 4 studies 8 that 4 studies 9 affect 4 studies 12 investigate 5 of 7 variants 6 gene 7 variants 8 that 9 affect 9 affect 11 activity 10 estrogen 11 activity 12 investigate 14 association 12 investigate 15 with 12 investigate 17 at 12 investigate 26 in 13 their 14 association 15 with 16 age 17 at 22 disease 18 onset 20 alzheimer 20 alzheimer 21 's 21 's 22 disease 22 disease 24 ad 23 ( 24 ad 24 ad 25 ) 26 in 27 women 27 women 28 of 28 of 30 ethnicities 29 different 30 ethnicities we investigated the influence of esr2 polymorphisms on age at onset [of] ad in a multiethnic cohort of women . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 investigated 0 ###LEFT-WALL### 20 . 1 we 2 investigated 2 investigated 4 influence 2 investigated 8 on 2 investigated 10 at 2 investigated 14 in 3 the 4 influence 4 influence 5 of 5 of 7 polymorphisms 6 esr2 7 polymorphisms 8 on 9 age 10 at 13 ad 11 onset 13 ad 14 in 17 cohort 15 a 16 multiethnic 15 a 17 cohort 16 multiethnic 17 cohort 17 cohort 18 of 18 of 19 women objectives : to determine whether gene variants would affect risk for ad differently in women of different population ancestries . 0 ###LEFT-WALL### 1 objectives 0 ###LEFT-WALL### 2 : 2 : 3 to 2 : 4 determine 2 : 20 . 3 to 4 determine 4 determine 5 whether 5 whether 7 variants 5 whether 9 affect 6 gene 7 variants 7 variants 8 would 8 would 9 affect 9 affect 10 risk 9 affect 13 differently 10 risk 11 for 11 for 12 ad 13 differently 14 in 14 in 15 women 15 women 16 of 16 of 19 ancestries 17 different 18 population 18 population 19 ancestries methods : among 1,686 women participating in the washington heights inwood columbia aging project ( whicap ) [,] association with risk for ad was [assessed] for 20 esr2 single - nucleotide polymorphisms ( snps ) using multivariate logistic regression , adjusting for age at time of study enrollment , presence of an apoe ε4 allele , years of education , and body mass index . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 1 methods 2 : 2 : 3 among 3 among 5 women 4 1,686 5 women 5 women 6 participating 5 women 7 in 7 in 13 aging 8 the 13 aging 9 washington 10 heights 10 heights 11 inwood 11 inwood 12 columbia 12 columbia 13 aging 13 aging 19 association 13 aging 24 was 14 project 16 whicap 14 project 19 association 15 ( 16 whicap 16 whicap 17 ) 19 association 20 with 19 association 22 for 19 association 24 was 20 with 21 risk 22 for 23 ad 24 was 26 for 24 was 36 using 26 for 32 polymorphisms 27 20 28 esr2 28 esr2 31 nucleotide 29 single 30 - 29 single 31 nucleotide 31 nucleotide 32 polymorphisms 32 polymorphisms 34 snps 33 ( 34 snps 34 snps 35 ) 36 using 39 regression 36 using 42 for 36 using 44 at 37 multivariate 39 regression 38 logistic 39 regression 39 regression 41 adjusting 40 , 41 adjusting 42 for 43 age 44 at 45 time 45 time 46 of 45 time 50 presence 45 time 57 years 46 of 48 enrollment 47 study 48 enrollment 49 , 50 presence 50 presence 51 of 50 presence 56 , 51 of 55 allele 52 an 55 allele 53 apoe 55 allele 54 ε4 55 allele 56 , 57 years 57 years 58 of 57 years 65 . 58 of 61 and 59 education 61 and 60 , 61 and 61 and 64 index 62 body 64 index 63 mass 64 index results : increased risk for ad was associated with four esr2 snps in women of [predominantly] caucasian aims - defined ancestry : rs944045 , rs1256062 , rs10144225 , and rs2274705 ( or range 1.6 - 1.9 , [empiric] p - value range 0.002 - 0.004 ) . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 8 associated 2 : 4 risk 3 increased 4 risk 4 risk 5 for 4 risk 7 was 5 for 6 ad 7 was 8 associated 8 associated 9 with 9 with 10 four 9 with 12 snps 11 esr2 12 snps 12 snps 13 in 12 snps 15 of 12 snps 21 ancestry 12 snps 22 : 13 in 14 women 15 of 18 aims 17 caucasian 18 aims 18 aims 20 defined 19 - 20 defined 21 ancestry 22 : 22 : 29 and 23 rs944045 24 , 24 , 25 rs1256062 24 , 26 , 26 , 27 rs10144225 26 , 29 and 28 , 29 and 29 and 30 rs2274705 30 rs2274705 35 - 31 ( 35 - 32 or 33 range 33 range 34 1.6 33 range 35 - 35 - 36 1.9 35 - 47 . 36 1.9 40 - 37 , 40 - 39 p 40 - 40 - 42 range 40 - 46 ) 41 value 42 range 42 range 44 - 43 0.002 44 - 44 - 45 0.004 a separate snp ( rs10137185 ) was associated with decreased risk for ad in women who identified themselves as black ( or 0.6 , 95 % ci = 0.4 - 0.9 ) . 0 ###LEFT-WALL### 3 snp 0 ###LEFT-WALL### 8 associated 0 ###LEFT-WALL### 33 . 1 a 3 snp 2 separate 3 snp 3 snp 5 rs10137185 3 snp 7 was 4 ( 5 rs10137185 5 rs10137185 6 ) 7 was 8 associated 8 associated 9 with 8 associated 14 in 8 associated 19 as 9 with 11 risk 10 decreased 11 risk 11 risk 12 for 12 for 13 ad 14 in 15 women 15 women 16 who 15 women 17 identified 16 who 17 identified 17 identified 18 themselves 19 as 20 black 20 black 22 or 21 ( 22 or 22 or 23 0.6 22 or 27 ci 22 or 32 ) 24 , 27 ci 25 95 27 ci 26 % 27 ci 27 ci 30 - 27 ci 32 ) 28 = 29 0.4 29 0.4 30 - 30 - 31 0.9 when vascular risk factors were included in the model , a separate snp ( rs1256059 ) was associated with increased risk for ad in women of admixed/hispanic ancestry [(] or 1.5 , 95 % ci = 1.1 - 2.4 ) . 0 ###LEFT-WALL### 13 snp 0 ###LEFT-WALL### 18 associated 0 ###LEFT-WALL### 41 . 1 when 4 factors 1 when 6 included 1 when 10 , 1 when 13 snp 2 vascular 4 factors 3 risk 4 factors 4 factors 5 were 5 were 6 included 6 included 7 in 7 in 9 model 8 the 9 model 11 a 12 separate 11 a 13 snp 12 separate 13 snp 13 snp 15 rs1256059 13 snp 17 was 14 ( 15 rs1256059 15 rs1256059 16 ) 17 was 18 associated 18 associated 19 with 18 associated 22 for 19 with 21 risk 20 increased 21 risk 22 for 23 ad 23 ad 24 in 23 ad 26 of 24 in 25 women 26 of 30 or 27 admixed/hispanic 30 or 28 ancestry 30 or 30 or 31 1.5 30 or 34 % 32 , 34 % 33 95 34 % 34 % 35 ci 34 % 36 = 34 % 40 ) 35 ci 36 = 36 = 38 - 37 1.1 38 - 38 - 39 2.4 conclusions : esr2 polymorphisms affect risk for ad in women , and risk alleles vary by aims - defined ancestry [and] self - identified ethnicity . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 4 polymorphisms 2 : 5 affect 2 : 12 and 2 : 18 - 3 esr2 4 polymorphisms 4 polymorphisms 5 affect 5 affect 6 risk 5 affect 7 for 5 affect 9 in 7 for 8 ad 9 in 10 women 11 , 12 and 12 and 14 alleles 12 and 15 vary 13 risk 14 alleles 14 alleles 15 vary 15 vary 16 by 16 by 17 aims 18 - 22 self 18 - 23 - 18 - 26 . 19 defined 20 ancestry 20 ancestry 22 self 23 - 25 ethnicity 24 identified 25 ethnicity these effects are possibly due to different linkage disequilibrium patterns or differences in comorbid risk factors mediating snp effect on risk for ad by group . 0 ###LEFT-WALL### 2 effects 0 ###LEFT-WALL### 3 are 0 ###LEFT-WALL### 11 or 0 ###LEFT-WALL### 26 . 1 these 2 effects 2 effects 3 are 3 are 4 possibly 3 are 6 to 5 due 6 to 6 to 10 patterns 7 different 8 linkage 8 linkage 10 patterns 9 disequilibrium 10 patterns 11 or 12 differences 11 or 25 group 12 differences 13 in 12 differences 25 group 13 in 14 comorbid 14 comorbid 15 risk 14 comorbid 16 factors 15 risk 16 factors 16 factors 19 effect 16 factors 24 by 17 mediating 19 effect 18 snp 19 effect 19 effect 20 on 20 on 21 risk 21 risk 22 for 22 for 23 ad late - onset alzheimer 's disease ( load ) is the most common neurodegenerative disorder in older adults , affecting over 50 % of those over age 85 . 0 ###LEFT-WALL### 6 disease 0 ###LEFT-WALL### 10 is 1 late 2 - 1 late 3 onset 3 onset 4 alzheimer 4 alzheimer 5 's 5 's 6 disease 6 disease 8 load 6 disease 10 is 7 ( 8 load 8 load 9 ) 10 is 15 disorder 11 the 15 disorder 12 most 13 common 13 common 15 disorder 14 neurodegenerative 15 disorder 15 disorder 16 in 15 disorder 20 affecting 16 in 18 adults 17 older 18 adults 19 , 20 affecting 20 affecting 23 % 20 affecting 26 over 20 affecting 29 . 21 over 22 50 22 50 23 % 23 % 24 of 24 of 25 those 26 over 27 age 27 age 28 85 aging is the most important risk factor for the development of load . 0 ###LEFT-WALL### 1 aging 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 13 . 1 aging 2 is 2 is 7 factor 3 the 7 factor 4 most 5 important 5 important 7 factor 6 risk 7 factor 7 factor 8 for 8 for 10 development 9 the 10 development 10 development 11 of 11 of 12 load aging is associated with the decrease in the ability of cells to cope with cellular stress , especially protein aggregation . 0 ###LEFT-WALL### 1 aging 0 ###LEFT-WALL### 3 associated 1 aging 2 is 2 is 3 associated 3 associated 4 with 3 associated 7 in 4 with 6 decrease 5 the 6 decrease 7 in 9 ability 8 the 9 ability 9 ability 10 of 9 ability 12 to 9 ability 13 cope 10 of 11 cells 12 to 13 cope 13 cope 14 with 14 with 16 stress 15 cellular 16 stress 16 stress 20 aggregation 17 , 18 especially 17 , 20 aggregation 19 protein 20 aggregation 20 aggregation 21 . here we describe how the process of aging affects pathways that control the processing and degradation of abnormal proteins including amyloid - β ( aβ ) . 0 ###LEFT-WALL### 2 we 0 ###LEFT-WALL### 3 describe 0 ###LEFT-WALL### 27 . 1 here 2 we 2 we 3 describe 3 describe 4 how 4 how 6 process 4 how 9 affects 5 the 6 process 6 process 7 of 6 process 9 affects 7 of 8 aging 9 affects 10 pathways 10 pathways 11 that 10 pathways 12 control 10 pathways 17 of 10 pathways 25 aβ 11 that 12 control 12 control 15 and 13 the 14 processing 14 processing 15 and 15 and 16 degradation 17 of 19 proteins 18 abnormal 19 proteins 19 proteins 20 including 20 including 23 β 21 amyloid 22 - 21 amyloid 23 β 24 ( 25 aβ 25 aβ 26 ) genetic association studies in load have successfully identified a large number of genetic variants involved in the development of the disease . 0 ###LEFT-WALL### 3 studies 0 ###LEFT-WALL### 8 identified 0 ###LEFT-WALL### 22 . 1 genetic 2 association 2 association 3 studies 3 studies 4 in 3 studies 6 have 4 in 5 load 6 have 8 identified 7 successfully 8 identified 8 identified 14 variants 9 a 10 large 9 a 11 number 10 large 11 number 11 number 12 of 11 number 14 variants 12 of 14 variants 13 genetic 14 variants 14 variants 15 involved 14 variants 19 of 15 involved 16 in 16 in 18 development 17 the 18 development 19 of 21 disease 20 the 21 disease however , there is a gap in understanding the interconnections between these pathomolecular events that prevent us from discovering therapeutic targets . 0 ###LEFT-WALL### 3 there 0 ###LEFT-WALL### 4 is 0 ###LEFT-WALL### 22 . 1 however 2 , 1 however 3 there 3 there 4 is 4 is 6 gap 5 a 6 gap 6 gap 7 in 7 in 8 understanding 8 understanding 10 interconnections 8 understanding 11 between 9 the 10 interconnections 11 between 14 events 12 these 14 events 13 pathomolecular 14 events 14 events 15 that 14 events 16 prevent 15 that 16 prevent 16 prevent 17 us 16 prevent 18 from 18 from 19 discovering 19 discovering 21 targets 20 therapeutic 21 targets we propose novel , pertinent links to elucidate [how] the biology of aging [affects] the sequence of events in the development of load . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 propose 0 ###LEFT-WALL### 24 . 1 we 2 propose 2 propose 6 links 2 propose 7 to 3 novel 4 , 3 novel 6 links 5 pertinent 6 links 7 to 8 elucidate 8 elucidate 11 biology 8 elucidate 19 in 10 the 11 biology 11 biology 12 of 12 of 13 aging 13 aging 16 sequence 15 the 16 sequence 16 sequence 17 of 17 of 18 events 19 in 21 development 20 the 21 development 21 development 22 of 22 of 23 load furthermore we analyze [and] [synthesize] the molecular - pathologic - clinical correlations of the aging process , involving the hsf1 and foxo family pathways , aβ metabolic pathway , and the different clinical stages of load . 0 ###LEFT-WALL### 2 we 0 ###LEFT-WALL### 3 analyze 1 furthermore 2 we 2 we 3 analyze 3 analyze 12 correlations 3 analyze 18 involving 6 the 12 correlations 7 molecular 8 - 7 molecular 12 correlations 9 pathologic 10 - 9 pathologic 12 correlations 11 clinical 12 correlations 12 correlations 13 of 13 of 16 process 14 the 16 process 15 aging 16 process 17 , 18 involving 18 involving 30 and 18 involving 37 . 19 the 30 and 20 hsf1 21 and 21 and 24 pathways 21 and 25 , 22 foxo 23 family 23 family 24 pathways 25 , 28 pathway 25 , 30 and 26 aβ 28 pathway 27 metabolic 28 pathway 29 , 30 and 30 and 34 stages 30 and 35 of 31 the 34 stages 32 different 34 stages 33 clinical 34 stages 35 of 36 load our new model postulates that the aging process would precede aβ accumulation , and attenuation of hsf1 is an " upstream " event in the cascade that results in excess aβ and synaptic dysfunction , which may lead to cognitive impairment [and/or] trigger " downstream " neurodegeneration and synaptic loss . 0 ###LEFT-WALL### 3 model 0 ###LEFT-WALL### 4 postulates 0 ###LEFT-WALL### 13 , 0 ###LEFT-WALL### 43 trigger 0 ###LEFT-WALL### 51 . 1 our 3 model 2 new 3 model 3 model 4 postulates 4 postulates 5 that 5 that 8 process 5 that 10 precede 6 the 8 process 7 aging 8 process 8 process 9 would 9 would 10 precede 10 precede 12 accumulation 11 aβ 12 accumulation 13 , 14 and 13 , 28 results 14 and 15 attenuation 14 and 18 is 15 attenuation 16 of 15 attenuation 18 is 16 of 17 hsf1 18 is 23 event 18 is 24 in 19 an 20 " 19 an 23 event 21 upstream 22 " 21 upstream 23 event 24 in 26 cascade 25 the 26 cascade 27 that 28 results 28 results 29 in 29 in 30 excess 30 excess 32 and 30 excess 43 trigger 31 aβ 32 and 32 and 34 dysfunction 32 and 35 , 32 and 36 which 32 and 37 may 32 and 43 trigger 33 synaptic 34 dysfunction 36 which 37 may 37 may 38 lead 38 lead 39 to 39 to 41 impairment 40 cognitive 41 impairment 43 trigger 44 " 43 trigger 48 and 45 downstream 46 " 45 downstream 47 neurodegeneration 47 neurodegeneration 48 and 48 and 50 loss 49 synaptic 50 loss specific host factors , such as the activity of foxo family pathways , would mediate the response to aβ toxicity and the pace of progression toward the clinical manifestations of ad . 0 ###LEFT-WALL### 3 factors 0 ###LEFT-WALL### 15 mediate 0 ###LEFT-WALL### 32 . 1 specific 2 host 2 host 3 factors 3 factors 6 as 3 factors 14 would 4 , 6 as 5 such 6 as 6 as 8 activity 6 as 13 , 7 the 8 activity 8 activity 9 of 9 of 12 pathways 10 foxo 11 family 11 family 12 pathways 14 would 15 mediate 15 mediate 17 response 15 mediate 18 to 15 mediate 26 toward 16 the 17 response 18 to 21 and 19 aβ 20 toxicity 20 toxicity 21 and 21 and 23 pace 21 and 24 of 22 the 23 pace 24 of 25 progression 26 toward 29 manifestations 27 the 29 manifestations 28 clinical 29 manifestations 29 manifestations 30 of 30 of 31 ad although mammalian long [non] - coding ( lnc )rnas [are] best known for modulating transcription , their post - transcriptional influence on mrna splicing , stability and translation is emerging . 0 ###LEFT-WALL### 21 influence 0 ###LEFT-WALL### 29 is 0 ###LEFT-WALL### 31 . 1 although 6 coding 1 although 21 influence 2 mammalian 6 coding 3 long 5 - 3 long 6 coding 6 coding 9 )rnas 6 coding 18 post 7 ( 9 )rnas 8 lnc 9 )rnas 9 )rnas 12 known 9 )rnas 16 , 11 best 12 known 12 known 13 for 13 for 15 transcription 14 modulating 15 transcription 16 , 18 post 17 their 18 post 18 post 19 - 20 transcriptional 21 influence 21 influence 22 on 21 influence 29 is 22 on 27 and 23 mrna 24 splicing 23 mrna 25 , 25 , 26 stability 25 , 27 and 27 and 28 translation 29 is 30 emerging here we report a post - translational [function] for the lncrna hotair as an inducer of ubiquitin - mediated proteolysis . 0 ###LEFT-WALL### 2 we 0 ###LEFT-WALL### 3 report 0 ###LEFT-WALL### 21 . 1 here 2 we 2 we 3 report 3 report 5 post 3 report 19 mediated 4 a 5 post 5 post 7 translational 5 post 19 mediated 6 - 7 translational 7 translational 9 for 7 translational 13 as 7 translational 18 - 9 for 12 hotair 10 the 11 lncrna 11 lncrna 12 hotair 13 as 15 inducer 14 an 15 inducer 15 inducer 16 of 16 of 17 ubiquitin 19 mediated 20 proteolysis hotair associates with e3 ubiquitin ligases bearing rna - binding domains , dzip3 and mex3b , as well as with their respective ubiquitination substrates , ataxin - 1 and [snurportin] - 1 . 0 ###LEFT-WALL### 1 hotair 0 ###LEFT-WALL### 2 associates 0 ###LEFT-WALL### 33 . 1 hotair 2 associates 2 associates 3 with 2 associates 29 and 3 with 6 ligases 4 e3 6 ligases 5 ubiquitin 6 ligases 6 ligases 7 bearing 6 ligases 19 as 7 bearing 8 rna 7 bearing 17 as 8 rna 10 binding 8 rna 15 mex3b 9 - 10 binding 10 binding 11 domains 10 binding 12 , 12 , 15 mex3b 13 dzip3 14 and 14 and 15 mex3b 15 mex3b 16 , 17 as 18 well 19 as 20 with 20 with 24 substrates 21 their 24 substrates 22 respective 24 substrates 23 ubiquitination 24 substrates 24 substrates 26 ataxin 25 , 26 ataxin 26 ataxin 27 - 28 1 29 and 29 and 32 1 31 - 32 1 in this manner , hotair facilitates the ubiquitination of ataxin - 1 by dzip3 and snurportin - [1] by mex3b in cells [and] in vitro , and accelerates their degradation . 0 ###LEFT-WALL### 5 hotair 0 ###LEFT-WALL### 27 and 0 ###LEFT-WALL### 31 . 1 in 3 manner 1 in 4 , 1 in 5 hotair 2 this 3 manner 5 hotair 27 and 6 facilitates 8 ubiquitination 6 facilitates 19 by 6 facilitates 21 in 6 facilitates 25 vitro 6 facilitates 27 and 7 the 8 ubiquitination 8 ubiquitination 9 of 9 of 10 ataxin 10 ataxin 12 1 11 - 12 1 12 1 13 by 12 1 17 - 13 by 15 and 14 dzip3 15 and 15 and 16 snurportin 19 by 20 mex3b 21 in 22 cells 24 in 25 vitro 26 , 27 and 27 and 28 accelerates 28 accelerates 30 degradation 29 their 30 degradation hotair levels are highly upregulated in senescent cells , causing rapid decay of targets ataxin - 1 [and] snurportin - 1 , and preventing premature senescence . 0 ###LEFT-WALL### 1 hotair 0 ###LEFT-WALL### 5 upregulated 0 ###LEFT-WALL### 27 . 1 hotair 2 levels 1 hotair 3 are 1 hotair 5 upregulated 2 levels 3 are 3 are 4 highly 5 upregulated 6 in 5 upregulated 10 causing 5 upregulated 23 and 6 in 8 cells 7 senescent 8 cells 9 , 10 causing 10 causing 12 decay 10 causing 16 - 11 rapid 12 decay 12 decay 13 of 13 of 15 ataxin 14 targets 15 ataxin 17 1 23 and 19 snurportin 21 1 19 snurportin 23 and 20 - 21 1 21 1 22 , 22 , 23 and 23 and 26 senescence 24 preventing 26 senescence 25 premature 26 senescence these results uncover a role for a lncrna , hotair , as a platform for protein ubiquitination . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 uncover 0 ###LEFT-WALL### 18 . 1 these 2 results 2 results 3 uncover 3 uncover 5 role 3 uncover 12 as 4 a 5 role 5 role 6 for 6 for 8 lncrna 7 a 8 lncrna 8 lncrna 10 hotair 9 , 10 hotair 10 hotair 11 , 12 as 14 platform 13 a 14 platform 14 platform 15 for 15 for 17 ubiquitination 16 protein 17 ubiquitination the binding affinities of the compounds were additionally determined using the inverse agonist [[] ( 3 )h ] - cgp - 12177 as the marker [ligand] and the ability of the compounds to stimulate camp accumulation , measured as ec₅₀ values , were determined in hek293 cells expressing the β₂ - ar . 1 the 3 affinities 2 binding 3 affinities 3 affinities 4 of 3 affinities 7 were 4 of 6 compounds 5 the 6 compounds 7 were 8 additionally 7 were 9 determined 9 determined 10 using 9 determined 21 - 10 using 13 agonist 11 the 13 agonist 12 inverse 13 agonist 13 agonist 17 )h 15 ( 17 )h 16 3 17 )h 17 )h 18 ] 19 - 21 - 20 cgp 21 - 21 - 22 12177 22 12177 23 as 22 12177 33 to 22 12177 34 stimulate 23 as 27 and 24 the 25 marker 25 marker 27 and 27 and 29 ability 28 the 29 ability 29 ability 30 of 30 of 32 compounds 31 the 32 compounds 33 to 34 stimulate 34 stimulate 35 camp 35 camp 36 accumulation 35 camp 42 , 36 accumulation 38 measured 36 accumulation 42 , 37 , 38 measured 38 measured 39 as 39 as 40 ec₅₀ 41 values 42 , 42 , 43 were 43 were 44 determined 44 determined 45 in 45 in 47 cells 46 hek293 47 cells 47 cells 48 expressing 48 expressing 50 β₂ 49 the 50 β₂ 50 β₂ 52 ar 51 - 52 ar 52 ar 53 . the data indicate that the highest binding affinities and functional activities were produced by methyl and ethyl substituents at the α ['] position . 0 ###LEFT-WALL### 2 data 0 ###LEFT-WALL### 3 indicate 0 ###LEFT-WALL### 16 and 0 ###LEFT-WALL### 24 . 1 the 2 data 2 data 3 indicate 3 indicate 4 that 4 that 9 and 4 that 13 produced 5 the 6 highest 5 the 8 affinities 7 binding 8 affinities 8 affinities 9 and 9 and 11 activities 9 and 12 were 10 functional 11 activities 12 were 13 produced 13 produced 14 by 14 by 15 methyl 16 and 17 ethyl 16 and 18 substituents 17 ethyl 18 substituents 18 substituents 19 at 19 at 23 position 20 the 23 position 21 α 23 position the results also indicate that the ki values obtained using [[] ( 3 )h []] - ( r,r ['] [ )(- methoxyfenoterol as the marker [ligand] modeled the ec₅₀ values obtained from camp stimulation better than the data obtained using [ [(] 3 )h ] - cgp - 12177 as the marker ligand . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 4 indicate 1 the 2 results 2 results 4 indicate 3 also 4 indicate 4 indicate 5 that 5 that 7 ki 5 that 8 values 6 the 7 ki 7 ki 8 values 8 values 10 using 9 obtained 10 using 10 using 14 )h 10 using 21 )(- 12 ( 14 )h 13 3 14 )h 14 )h 16 - 17 ( 21 )(- 18 r,r 21 )(- 21 )(- 22 methoxyfenoterol 22 methoxyfenoterol 23 as 22 methoxyfenoterol 27 modeled 22 methoxyfenoterol 30 values 22 methoxyfenoterol 31 obtained 23 as 25 marker 24 the 25 marker 28 the 30 values 29 ec₅₀ 30 values 30 values 31 obtained 31 obtained 32 from 32 from 34 stimulation 33 camp 34 stimulation 34 stimulation 35 better 35 better 36 than 36 than 40 using 37 the 40 using 38 data 39 obtained 39 obtained 40 using 40 using 44 )h 40 using 47 cgp 41 [ 44 )h 43 3 44 )h 44 )h 45 ] 46 - 47 cgp 47 cgp 49 12177 47 cgp 53 ligand 47 cgp 54 . 48 - 49 12177 49 12177 50 as 49 12177 53 ligand 50 as 52 marker 51 the 52 marker the data from this study was combined with data from previous studies and processed using the comparative molecular field analysis approach to produce a comfa model reflecting the binding to the β₂ - ar conformation probed [by] [[] ( 3 )h ] - [(] r,r ['] ) - 4 ['] - methoxyfenoterol . 0 ###LEFT-WALL### 2 data 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 53 . 1 the 2 data 2 data 3 from 2 data 13 and 3 from 5 study 4 this 5 study 6 was 7 combined 6 was 13 and 7 combined 8 with 8 with 9 data 9 data 10 from 10 from 12 studies 11 previous 12 studies 13 and 14 processed 13 and 15 using 13 and 52 methoxyfenoterol 15 using 21 approach 15 using 22 to 15 using 30 to 16 the 21 approach 17 comparative 18 molecular 18 molecular 21 approach 19 field 20 analysis 20 analysis 21 approach 22 to 23 produce 23 produce 26 model 24 a 26 model 25 comfa 26 model 26 model 27 reflecting 27 reflecting 29 binding 28 the 29 binding 30 to 35 conformation 31 the 35 conformation 32 β₂ 33 - 32 β₂ 35 conformation 34 ar 35 conformation 35 conformation 36 probed 35 conformation 41 )h 35 conformation 45 r,r 35 conformation 49 4 39 ( 41 )h 40 3 41 )h 41 )h 42 ] 43 - 45 r,r 45 r,r 47 ) 48 - 49 4 49 4 51 - a 56 [-] year [-] old woman presented with red - purple blotches on both forearms which had suddenly appeared without any pain , pruritus or trauma . 0 ###LEFT-WALL### 26 or 0 ###LEFT-WALL### 28 . 1 a 7 woman 2 56 4 year 4 year 7 woman 6 old 7 woman 7 woman 8 presented 7 woman 24 , 8 presented 9 with 9 with 13 blotches 10 red 11 - 10 red 13 blotches 12 purple 13 blotches 13 blotches 14 on 13 blotches 17 which 13 blotches 18 had 14 on 16 forearms 15 both 16 forearms 17 which 18 had 18 had 20 appeared 19 suddenly 20 appeared 20 appeared 21 without 21 without 23 pain 22 any 23 pain 24 , 25 pruritus 24 , 26 or 26 or 27 trauma laboratory investigation showed no abnormalities . 0 ###LEFT-WALL### 2 investigation 0 ###LEFT-WALL### 3 showed 0 ###LEFT-WALL### 6 . 1 laboratory 2 investigation 2 investigation 3 showed 3 showed 5 abnormalities 4 no 5 abnormalities histopathology revealed [non] - inflammatory actinic purpura . 0 ###LEFT-WALL### 1 histopathology 0 ###LEFT-WALL### 2 revealed 0 ###LEFT-WALL### 4 - 0 ###LEFT-WALL### 8 . 1 histopathology 2 revealed 2 revealed 4 - 4 - 7 purpura 5 inflammatory 7 purpura 6 actinic 7 purpura these purpura are frequently seen in older people due to a weakened collagen framework . 0 ###LEFT-WALL### 2 purpura 0 ###LEFT-WALL### 5 seen 0 ###LEFT-WALL### 15 . 1 these 2 purpura 2 purpura 3 are 3 are 5 seen 4 frequently 5 seen 5 seen 6 in 5 seen 10 to 6 in 8 people 7 older 8 people 9 due 10 to 10 to 14 framework 11 a 14 framework 12 weakened 14 framework 13 collagen 14 framework mitochondria grow , divide , [and] fuse in cells . 0 ###LEFT-WALL### 3 , 0 ###LEFT-WALL### 5 , 0 ###LEFT-WALL### 10 . 1 mitochondria 3 , 2 grow 3 , 3 , 4 divide 5 , 7 fuse 7 fuse 8 in 8 in 9 cells mitochondrial division is critical for the maintenance of the structure and function of mitochondria . 0 ###LEFT-WALL### 2 division 0 ###LEFT-WALL### 3 is 0 ###LEFT-WALL### 15 . 1 mitochondrial 2 division 2 division 3 is 3 is 4 critical 4 critical 5 for 5 for 7 maintenance 6 the 7 maintenance 7 maintenance 8 of 8 of 11 and 9 the 10 structure 10 structure 11 and 11 and 12 function 11 and 13 of 13 of 14 mitochondria alterations in this process have been linked to many human diseases , including peripheral neuropathies and aging - related neurological disorders . 0 ###LEFT-WALL### 1 alterations 0 ###LEFT-WALL### 7 linked 0 ###LEFT-WALL### 19 related 1 alterations 2 in 1 alterations 5 have 2 in 4 process 3 this 4 process 5 have 6 been 6 been 7 linked 7 linked 8 to 7 linked 13 including 8 to 11 diseases 9 many 11 diseases 10 human 11 diseases 12 , 13 including 13 including 16 and 13 including 18 - 14 peripheral 15 neuropathies 15 neuropathies 16 and 16 and 17 aging 18 - 19 related 19 related 21 disorders 19 related 22 . 20 neurological 21 disorders in this review , we discuss recent progress in mitochondrial division by focusing on [molecular] and in [vivo] analyses of the evolutionarily conserved [,] central component of mitochondrial division , dynamin - related protein 1 ( drp1 ) , in the yeast and mouse model organisms . 0 ###LEFT-WALL### 5 we 0 ###LEFT-WALL### 6 discuss 0 ###LEFT-WALL### 33 related 1 in 3 review 1 in 4 , 1 in 5 we 2 this 3 review 5 we 6 discuss 6 discuss 8 progress 7 recent 8 progress 8 progress 9 in 8 progress 12 by 9 in 11 division 10 mitochondrial 11 division 12 by 13 focusing 13 focusing 16 and 14 on 16 and 16 and 17 in 16 and 19 analyses 19 analyses 20 of 19 analyses 27 of 20 of 26 component 21 the 26 component 22 evolutionarily 23 conserved 23 conserved 26 component 25 central 26 component 27 of 29 division 28 mitochondrial 29 division 29 division 31 dynamin 30 , 31 dynamin 31 dynamin 32 - 32 - 33 related 33 related 34 protein 33 related 47 . 34 protein 35 1 34 protein 37 drp1 34 protein 40 in 36 ( 37 drp1 37 drp1 38 ) 39 , 40 in 40 in 43 and 40 in 47 . 41 the 42 yeast 42 yeast 43 and 43 and 46 organisms 44 mouse 46 organisms 45 model 46 organisms objectives : to investigate the association of mood [and] anxiety symptoms with sleep architecture ( the distribution of sleep stages ) in community [-] dwelling older men . 0 ###LEFT-WALL### 1 objectives 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 28 . 2 : 3 to 2 : 4 investigate 3 to 4 investigate 4 investigate 6 association 4 investigate 22 in 5 the 6 association 6 association 7 of 7 of 11 symptoms 8 mood 11 symptoms 10 anxiety 11 symptoms 11 symptoms 12 with 12 with 14 architecture 13 sleep 14 architecture 14 architecture 17 distribution 15 ( 17 distribution 16 the 17 distribution 17 distribution 18 of 17 distribution 21 ) 18 of 20 stages 19 sleep 20 stages 22 in 27 men 23 community 25 dwelling 25 dwelling 27 men 26 older 27 men method : we used in [-] home unattended polysomnography to measure sleep architecture in older men . 0 ###LEFT-WALL### 1 method 0 ###LEFT-WALL### 2 : 2 : 3 we 2 : 4 used 2 : 17 . 3 we 4 used 4 used 5 in 4 used 9 polysomnography 4 used 10 to 5 in 7 home 8 unattended 9 polysomnography 10 to 11 measure 11 measure 13 architecture 11 measure 14 in 12 sleep 13 architecture 14 in 16 men 15 older 16 men men were categorized into 4 mental health categories : [(] a [ )(significant depressive symptoms only [(] dep+ only , geriatric depression scale [≥] [6] [ )(, [(] [b] [ )(significant anxiety symptoms only [(] anx+ only , goldberg anxiety scale [≥] [5] [ )(, [(] [c] [ )(significant depressive and anxiety symptoms ( dep+/anx+ ) , [or] [(] [d] [ )(no significant depressive or anxiety symptoms ( dep - /anx - [ )( 0 ###LEFT-WALL### 1 men 0 ###LEFT-WALL### 9 : 1 men 2 were 2 were 3 categorized 3 categorized 4 into 4 into 8 categories 5 4 8 categories 6 mental 7 health 7 health 8 categories 9 : 14 depressive 9 : 20 , 11 a 14 depressive 13 )(significant 14 depressive 14 depressive 15 symptoms 14 depressive 18 dep+ 15 symptoms 18 dep+ 16 only 18 dep+ 18 dep+ 19 only 20 , 23 scale 20 , 27 )(, 21 geriatric 22 depression 22 depression 23 scale 27 )(, 33 symptoms 27 )(, 38 , 31 )(significant 32 anxiety 32 anxiety 33 symptoms 33 symptoms 36 anx+ 34 only 36 anx+ 36 anx+ 37 only 38 , 41 scale 38 , 45 )(, 39 goldberg 40 anxiety 40 anxiety 41 scale 45 )(, 51 and 45 )(, 57 , 49 )(significant 50 depressive 50 depressive 51 and 51 and 53 symptoms 51 and 55 dep+/anx+ 52 anxiety 53 symptoms 54 ( 55 dep+/anx+ 55 dep+/anx+ 56 ) 57 , 65 or 62 )(no 64 depressive 63 significant 64 depressive 64 depressive 65 or 65 or 67 symptoms 65 or 69 dep 66 anxiety 67 symptoms 68 ( 69 dep 69 dep 71 /anx 69 dep 74 )( 70 - 71 /anx 71 /anx 72 - these differences persisted after adjustment for demographic/lifestyle characteristics , medical conditions , medications , and sleep disturbances , and after excluding participants using psychotropic medications . 0 ###LEFT-WALL### 2 differences 0 ###LEFT-WALL### 3 persisted 0 ###LEFT-WALL### 26 . 1 these 2 differences 2 differences 3 persisted 3 persisted 4 after 4 after 5 adjustment 5 adjustment 19 and 6 for 15 and 6 for 19 and 7 demographic/lifestyle 8 characteristics 8 characteristics 9 , 9 , 11 conditions 9 , 12 , 10 medical 11 conditions 12 , 13 medications 12 , 15 and 14 , 15 and 15 and 17 disturbances 16 sleep 17 disturbances 18 , 19 and 19 and 20 after 20 after 21 excluding 21 excluding 22 participants 21 excluding 23 using 23 using 25 medications 24 psychotropic 25 medications the sleep architecture of anx+ or dep+/anx+ men did not differ from asymptomatic men . 0 ###LEFT-WALL### 3 architecture 0 ###LEFT-WALL### 11 differ 0 ###LEFT-WALL### 15 . 1 the 3 architecture 2 sleep 3 architecture 3 architecture 4 of 3 architecture 9 did 4 of 6 or 5 anx+ 6 or 6 or 8 men 7 dep+/anx+ 8 men 9 did 10 not 9 did 11 differ 11 differ 12 from 12 from 14 men 13 asymptomatic 14 men discussion : depressed [mood] in older adults may be associated with accelerated age - related changes in sleep architecture . 0 ###LEFT-WALL### 1 discussion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 20 . 2 : 3 depressed 2 : 10 associated 2 : 15 related 3 depressed 5 in 3 depressed 8 may 5 in 7 adults 6 older 7 adults 8 may 9 be 9 be 10 associated 10 associated 11 with 11 with 13 age 12 accelerated 13 age 14 - 15 related 15 related 16 changes 16 changes 17 in 17 in 19 architecture 18 sleep 19 architecture longitudinal community - based studies using diagnostic measures are needed to further clarify relationships among common mental disorders , aging , and sleep . 0 ###LEFT-WALL### 2 community 0 ###LEFT-WALL### 3 - 0 ###LEFT-WALL### 24 . 1 longitudinal 2 community 3 - 4 based 3 - 22 and 4 based 9 are 4 based 11 to 5 studies 6 using 5 studies 9 are 6 using 8 measures 7 diagnostic 8 measures 9 are 10 needed 11 to 22 and 12 further 13 clarify 13 clarify 14 relationships 13 clarify 20 aging 13 clarify 22 and 14 relationships 15 among 15 among 18 disorders 16 common 18 disorders 17 mental 18 disorders 19 , 20 aging 20 aging 21 , 21 , 22 and 22 and 23 sleep unlabelled : fine structural details of glycans attached to the conserved [n] [-] glycosylation site significantly not only affect function [of] individual immunoglobulin g ( igg ) [molecules] but also mediate inflammation at the systemic level . 0 ###LEFT-WALL### 1 unlabelled 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 37 . 2 : 5 details 2 : 30 also 3 fine 5 details 4 structural 5 details 5 details 6 of 5 details 30 also 6 of 7 glycans 7 glycans 8 attached 8 attached 9 to 8 attached 16 significantly 9 to 15 site 10 the 15 site 11 conserved 14 glycosylation 14 glycosylation 15 site 17 not 18 only 18 only 30 also 19 affect 23 immunoglobulin 19 affect 30 also 20 function 22 individual 22 individual 23 immunoglobulin 23 immunoglobulin 24 g 23 immunoglobulin 26 igg 25 ( 26 igg 26 igg 27 ) 29 but 30 also 30 also 31 mediate 31 mediate 32 inflammation 31 mediate 33 at 33 at 36 level 34 the 36 level 35 systemic 36 level by analyzing igg glycosylation in 5,117 individuals from four european populations , we have revealed very complex patterns of changes in igg glycosylation with age . 0 ###LEFT-WALL### 13 we 0 ###LEFT-WALL### 15 revealed 0 ###LEFT-WALL### 26 . 1 by 2 analyzing 1 by 12 , 1 by 13 we 2 analyzing 4 glycosylation 3 igg 4 glycosylation 4 glycosylation 5 in 5 in 7 individuals 6 5,117 7 individuals 7 individuals 8 from 8 from 11 populations 9 four 11 populations 10 european 11 populations 13 we 14 have 14 have 15 revealed 15 revealed 18 patterns 15 revealed 21 in 15 revealed 24 with 16 very 17 complex 17 complex 18 patterns 18 patterns 19 of 19 of 20 changes 21 in 23 glycosylation 22 igg 23 glycosylation 24 with 25 age several igg glycans ( including fa2b , fa2g2 , and fa2bg2 ) changed considerably with age and the combination of these three glycans can explain up to 58 % of variance in chronological age , significantly more than other markers of biological age like telomere lengths . 0 ###LEFT-WALL### 1 several 0 ###LEFT-WALL### 17 and 1 several 2 igg 1 several 3 glycans 1 several 5 including 1 several 17 and 2 igg 3 glycans 4 ( 5 including 5 including 6 fa2b 5 including 12 ) 6 fa2b 10 and 7 , 10 and 8 fa2g2 10 and 9 , 10 and 10 and 11 fa2bg2 10 and 12 ) 13 changed 14 considerably 13 changed 15 with 13 changed 17 and 15 with 16 age 17 and 25 explain 17 and 32 in 18 the 19 combination 19 combination 20 of 19 combination 24 can 20 of 23 glycans 21 these 22 three 22 three 23 glycans 24 can 25 explain 25 explain 29 % 26 up 27 to 27 to 28 58 28 58 29 % 29 % 30 of 30 of 31 variance 32 in 34 age 33 chronological 34 age 34 age 37 more 35 , 37 more 36 significantly 37 more 37 more 38 than 37 more 47 . 38 than 40 markers 39 other 40 markers 40 markers 41 of 41 of 43 age 42 biological 43 age 43 age 44 like 44 like 46 lengths 45 telomere 46 lengths the remaining variance in these glycans strongly correlated with physiological parameters associated with biological age . 0 ###LEFT-WALL### 3 variance 0 ###LEFT-WALL### 8 correlated 0 ###LEFT-WALL### 16 . 1 the 2 remaining 1 the 3 variance 3 variance 4 in 3 variance 8 correlated 4 in 6 glycans 5 these 6 glycans 7 strongly 8 correlated 8 correlated 9 with 9 with 11 parameters 10 physiological 11 parameters 11 parameters 12 associated 12 associated 13 with 13 with 15 age 14 biological 15 age thus , igg glycosylation appears to be closely linked with both chronological and biological ages . 0 ###LEFT-WALL### 4 glycosylation 0 ###LEFT-WALL### 5 appears 0 ###LEFT-WALL### 16 . 1 thus 2 , 1 thus 4 glycosylation 3 igg 4 glycosylation 4 glycosylation 5 appears 5 appears 6 to 6 to 7 be 7 be 8 closely 7 be 9 linked 9 linked 10 with 10 with 15 ages 11 both 15 ages 12 chronological 13 and 13 and 14 biological 13 and 15 ages considering the important role of igg glycans in inflammation , and because the observed changes with age promote inflammation , changes in igg glycosylation also seem to represent a factor contributing to aging . 0 ###LEFT-WALL### 1 considering 0 ###LEFT-WALL### 7 glycans 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 34 . 1 considering 4 role 1 considering 7 glycans 2 the 4 role 3 important 4 role 4 role 5 of 5 of 6 igg 7 glycans 8 in 8 in 9 inflammation 10 , 11 and 11 and 21 changes 11 and 26 seem 12 because 15 changes 12 because 18 promote 12 because 20 , 12 because 21 changes 13 the 15 changes 14 observed 15 changes 15 changes 16 with 15 changes 18 promote 16 with 17 age 18 promote 19 inflammation 21 changes 22 in 21 changes 26 seem 22 in 24 glycosylation 23 igg 24 glycosylation 25 also 26 seem 26 seem 27 to 26 seem 28 represent 27 to 28 represent 28 represent 30 factor 29 a 30 factor 30 factor 31 contributing 31 contributing 32 to 32 to 33 aging significance statement : glycosylation is the key posttranslational mechanism that regulates function [of] immunoglobulins , with multiple systemic repercussions to the immune system . 0 ###LEFT-WALL### 2 statement 0 ###LEFT-WALL### 3 : 1 significance 2 statement 3 : 4 glycosylation 3 : 5 is 4 glycosylation 5 is 5 is 9 mechanism 5 is 16 with 6 the 9 mechanism 7 key 9 mechanism 8 posttranslational 9 mechanism 9 mechanism 10 that 9 mechanism 11 regulates 10 that 11 regulates 11 regulates 14 immunoglobulins 12 function 14 immunoglobulins 15 , 16 with 16 with 19 repercussions 16 with 20 to 16 with 24 . 17 multiple 19 repercussions 18 systemic 19 repercussions 20 to 23 system 21 the 23 system 22 immune 23 system our study of igg glycosylation in 5,117 individuals from four european populations has revealed very extensive [and] complex changes in igg glycosylation with age . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 13 has 0 ###LEFT-WALL### 25 . 1 our 2 study 2 study 3 of 2 study 13 has 3 of 5 glycosylation 4 igg 5 glycosylation 5 glycosylation 6 in 5 glycosylation 9 from 6 in 8 individuals 7 5,117 8 individuals 9 from 12 populations 10 four 12 populations 11 european 12 populations 13 has 19 changes 14 revealed 19 changes 15 very 16 extensive 16 extensive 19 changes 18 complex 19 changes 19 changes 20 in 19 changes 23 with 20 in 22 glycosylation 21 igg 22 glycosylation 23 with 24 age the combined index composed of only three glycans explained up to 58 % of variance in age , considerably more than other biomarkers of age like telomere lengths . 0 ###LEFT-WALL### 3 index 0 ###LEFT-WALL### 9 explained 0 ###LEFT-WALL### 21 than 0 ###LEFT-WALL### 29 . 1 the 3 index 2 combined 3 index 3 index 4 composed 3 index 5 of 3 index 9 explained 5 of 8 glycans 6 only 7 three 7 three 8 glycans 9 explained 13 % 9 explained 16 in 10 up 11 to 11 to 12 58 12 58 13 % 13 % 14 of 14 of 15 variance 16 in 17 age 18 , 20 more 18 , 21 than 19 considerably 20 more 21 than 23 biomarkers 21 than 26 like 22 other 23 biomarkers 23 biomarkers 24 of 23 biomarkers 26 like 24 of 25 age 26 like 28 lengths 27 telomere 28 lengths the remaining variance in these glycans strongly correlated with physiological parameters associated with biological age ; thus , igg glycosylation appears to be closely linked with both chronological and biological ages . 0 ###LEFT-WALL### 3 variance 0 ###LEFT-WALL### 8 correlated 0 ###LEFT-WALL### 16 ; 0 ###LEFT-WALL### 32 . 1 the 3 variance 2 remaining 3 variance 3 variance 4 in 3 variance 8 correlated 4 in 6 glycans 5 these 6 glycans 7 strongly 8 correlated 8 correlated 9 with 9 with 11 parameters 9 with 13 with 10 physiological 11 parameters 11 parameters 12 associated 13 with 15 age 14 biological 15 age 16 ; 20 glycosylation 16 ; 21 appears 17 thus 20 glycosylation 18 , 19 igg 19 igg 20 glycosylation 20 glycosylation 21 appears 21 appears 22 to 21 appears 25 linked 22 to 23 be 23 be 25 linked 24 closely 25 linked 25 linked 26 with 26 with 31 ages 27 both 31 ages 28 chronological 29 and 29 and 30 biological 29 and 31 ages the ability to measure human biological aging using molecular profiling has practical applications for diverse fields such as disease prevention and treatment , or forensics . 0 ###LEFT-WALL### 2 ability 0 ###LEFT-WALL### 11 has 0 ###LEFT-WALL### 26 . 1 the 2 ability 2 ability 3 to 2 ability 4 measure 2 ability 11 has 3 to 4 measure 4 measure 7 aging 4 measure 8 using 5 human 7 aging 6 biological 7 aging 8 using 10 profiling 9 molecular 10 profiling 11 has 13 applications 11 has 14 for 11 has 18 as 12 practical 13 applications 14 for 16 fields 15 diverse 16 fields 17 such 18 as 18 as 24 or 19 disease 20 prevention 20 prevention 21 and 21 and 22 treatment 21 and 24 or 23 , 24 or 24 or 25 forensics posttranslational modifications of circulating proteins such as immunoglobulins may prove to be important biomarkers of aging . 0 ###LEFT-WALL### 2 modifications 0 ###LEFT-WALL### 10 prove 0 ###LEFT-WALL### 17 . 1 posttranslational 2 modifications 2 modifications 3 of 2 modifications 9 may 3 of 4 circulating 4 circulating 5 proteins 5 proteins 7 as 6 such 7 as 7 as 8 immunoglobulins 9 may 10 prove 10 prove 11 to 10 prove 12 be 11 to 12 be 12 be 14 biomarkers 13 important 14 biomarkers 14 biomarkers 15 of 15 of 16 aging background : it has been hypothesized that insulin resistance plays a role in the development of the loss of skeletal muscle ; however , no cohort studies on insulin resistance and low relative appendicular skeletal muscle mass ( asm ) have been published to date . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 3 it 2 : 6 hypothesized 2 : 22 ; 2 : 46 . 3 it 4 has 4 has 5 been 5 been 6 hypothesized 6 hypothesized 7 that 7 that 9 resistance 7 that 10 plays 8 insulin 9 resistance 9 resistance 10 plays 10 plays 12 role 10 plays 13 in 11 a 12 role 13 in 15 development 14 the 15 development 15 development 16 of 15 development 19 of 16 of 18 loss 17 the 18 loss 19 of 21 muscle 20 skeletal 21 muscle 22 ; 27 studies 22 ; 45 date 23 however 24 , 23 however 27 studies 25 no 27 studies 26 cohort 27 studies 27 studies 28 on 27 studies 39 asm 27 studies 41 have 28 on 31 and 29 insulin 30 resistance 30 resistance 31 and 31 and 37 mass 32 low 36 muscle 33 relative 36 muscle 34 appendicular 36 muscle 35 skeletal 36 muscle 36 muscle 37 mass 38 ( 39 asm 39 asm 40 ) 41 have 42 been 42 been 43 published 43 published 44 to 44 to 45 date thus , we examined whether insulin resistance is associated with low relative asm after a 4.6 [-] year [follow] - up period among apparently healthy older men and women participants . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 examined 0 ###LEFT-WALL### 20 - 0 ###LEFT-WALL### 31 . 1 thus 2 , 1 thus 3 we 3 we 4 examined 4 examined 5 whether 5 whether 7 resistance 5 whether 9 associated 6 insulin 7 resistance 7 resistance 8 is 8 is 9 associated 9 associated 10 with 9 associated 14 after 10 with 13 asm 11 low 13 asm 12 relative 13 asm 14 after 18 year 15 a 18 year 16 4.6 18 year 20 - 21 up 21 up 22 period 21 up 23 among 23 among 28 and 24 apparently 25 healthy 25 healthy 27 men 26 older 27 men 27 men 28 and 28 and 30 participants 29 women 30 participants methods : this is a combined retrospective - prospective cohort study , which includes 147 community [-] dwelling older men and women participants . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 24 . 2 : 3 this 2 : 4 is 2 : 12 , 3 this 4 is 4 is 11 study 5 a 11 study 6 combined 10 cohort 7 retrospective 8 - 7 retrospective 10 cohort 9 prospective 10 cohort 10 cohort 11 study 12 , 13 which 12 , 14 includes 13 which 14 includes 14 includes 21 and 15 147 20 men 16 community 18 dwelling 18 dwelling 20 men 19 older 20 men 20 men 21 and 21 and 23 participants 22 women 23 participants asm was measured by dual - energy x - ray absorptiometry at baseline and follow - up . 0 ###LEFT-WALL### 1 asm 0 ###LEFT-WALL### 2 was 0 ###LEFT-WALL### 9 - 1 asm 2 was 2 was 3 measured 3 measured 4 by 4 by 8 x 5 dual 6 - 5 dual 7 energy 7 energy 8 x 9 - 14 and 10 ray 11 absorptiometry 10 ray 12 at 10 ray 14 and 12 at 13 baseline 14 and 15 follow 15 follow 17 up 16 - 17 up 17 up 18 . participants with a relative change in asm below the sex - specific 15th value were classified as the low relative asm group . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 5 change 0 ###LEFT-WALL### 11 - 0 ###LEFT-WALL### 23 . 1 participants 2 with 1 participants 5 change 2 with 4 relative 3 a 4 relative 5 change 6 in 5 change 8 below 6 in 7 asm 8 below 10 sex 9 the 10 sex 11 - 12 specific 11 - 15 were 12 specific 13 15th 12 specific 15 were 14 value 15 were 15 were 16 classified 16 classified 17 as 17 as 22 group 18 the 22 group 19 low 22 group 20 relative 22 group 21 asm 22 group homeostatic model assessment was used to quantify insulin resistance . 0 ###LEFT-WALL### 3 assessment 0 ###LEFT-WALL### 5 used 0 ###LEFT-WALL### 10 . 1 homeostatic 3 assessment 2 model 3 assessment 3 assessment 4 was 4 was 5 used 5 used 6 to 5 used 7 quantify 6 to 7 quantify 7 quantify 9 resistance 8 insulin 9 resistance logistic regression calculated odds ratios and 95 % confidence intervals for development of low relative asm , adjusted for covariates . 0 ###LEFT-WALL### 2 regression 0 ###LEFT-WALL### 17 , 0 ###LEFT-WALL### 21 . 1 logistic 2 regression 2 regression 17 , 3 calculated 6 and 3 calculated 11 for 3 calculated 17 , 4 odds 5 ratios 5 ratios 6 and 6 and 10 intervals 7 95 10 intervals 8 % 9 confidence 9 confidence 10 intervals 11 for 12 development 12 development 13 of 13 of 16 asm 14 low 16 asm 15 relative 16 asm 17 , 18 adjusted 17 , 19 for 19 for 20 covariates results : the loss of asm in the low relative asm and normal groups was - 1.8 kg and - 0.35 kg , respectively [(] [p] ≤ . 05 [ )( 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 4 loss 2 : 15 was 2 : 23 , 2 : 27 ≤ 2 : 28 . 3 the 4 loss 4 loss 5 of 4 loss 15 was 5 of 12 and 6 asm 7 in 6 asm 12 and 7 in 11 asm 8 the 11 asm 9 low 11 asm 10 relative 11 asm 12 and 14 groups 13 normal 14 groups 15 was 19 and 16 - 17 1.8 17 1.8 18 kg 18 kg 19 and 19 and 22 kg 20 - 21 0.35 21 0.35 22 kg 23 , 27 ≤ 24 respectively 27 ≤ 28 . 29 05 28 . 31 )( the low relative asm group was older and had higher insulin and homeostatic model assessment of insulin resistance values at baseline . 0 ###LEFT-WALL### 5 group 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 22 . 1 the 5 group 2 low 5 group 3 relative 5 group 4 asm 5 group 5 group 8 and 6 was 7 older 6 was 8 and 8 and 9 had 8 and 20 at 9 had 12 and 10 higher 11 insulin 11 insulin 12 and 12 and 15 assessment 12 and 16 of 13 homeostatic 14 model 14 model 15 assessment 16 of 19 values 17 insulin 19 values 18 resistance 19 values 20 at 21 baseline the risk [of] developing low relative asm at 4.6 [-] year follow [-] up was 2.9 times higher ( 95 % ci [,] 1.00 - 7.8 [;] p = [.] 04 [ )(among the participants with homeostatic model assessment of insulin resistance levels more than 2.3 [.] 1 the 6 relative 2 risk 4 developing 4 developing 6 relative 5 low 6 relative 6 relative 7 asm 6 relative 12 follow 6 relative 15 was 7 asm 8 at 7 asm 12 follow 8 at 11 year 9 4.6 11 year 12 follow 14 up 15 was 17 times 16 2.9 17 times 17 times 18 higher 18 higher 25 - 18 higher 29 = 19 ( 25 - 20 95 22 ci 21 % 22 ci 22 ci 24 1.00 22 ci 25 - 25 - 26 7.8 28 p 29 = 29 = 31 04 31 04 33 )(among 31 04 40 of 31 04 42 resistance 31 04 43 levels 33 )(among 35 participants 34 the 35 participants 35 participants 36 with 36 with 39 assessment 37 homeostatic 39 assessment 38 model 39 assessment 40 of 41 insulin 42 resistance 43 levels 43 levels 44 more 43 levels 45 than 45 than 46 2.3 after adjusting for age , the risk increased to 3.9 times higher [(] 95 % ci , 1.3 - 11.5 [;] p = [.] 03 ) . 0 ###LEFT-WALL### 7 risk 0 ###LEFT-WALL### 11 times 0 ###LEFT-WALL### 27 . 1 after 2 adjusting 1 after 7 risk 3 for 4 age 3 for 5 , 3 for 7 risk 6 the 7 risk 7 risk 8 increased 7 risk 9 to 7 risk 11 times 9 to 10 3.9 11 times 12 higher 11 times 16 ci 14 95 16 ci 15 % 16 ci 16 ci 19 - 17 , 19 - 18 1.3 19 - 19 - 20 11.5 19 - 26 ) 20 11.5 23 = 22 p 23 = 23 = 25 03 conclusion : insulin resistance was associated with low relative asm at 4.6 - [year] follow - up after accounting for several covariates in a cohort of apparently healthy , well - functioning young older men and women . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 4 resistance 2 : 6 associated 2 : 13 - 3 insulin 4 resistance 4 resistance 5 was 5 was 6 associated 6 associated 7 with 6 associated 11 at 7 with 10 asm 8 low 9 relative 9 relative 10 asm 11 at 12 4.6 13 - 15 follow 13 - 16 - 16 - 17 up 16 - 38 . 17 up 18 after 17 up 22 covariates 18 after 19 accounting 19 accounting 20 for 20 for 21 several 22 covariates 23 in 22 covariates 26 of 23 in 25 cohort 24 a 25 cohort 26 of 36 and 27 apparently 28 healthy 28 healthy 30 well 28 healthy 31 - 28 healthy 35 men 29 , 30 well 30 well 31 - 32 functioning 35 men 33 young 34 older 34 older 35 men 35 men 36 and 36 and 37 women none amyotrophic lateral sclerosis ( als ) is as an adult [-] onset neurodegenerative disorder involving both upper and lower motor neurons . 0 ###LEFT-WALL### 1 none 0 ###LEFT-WALL### 22 neurons 0 ###LEFT-WALL### 23 . 1 none 4 sclerosis 1 none 8 is 1 none 22 neurons 2 amyotrophic 4 sclerosis 3 lateral 4 sclerosis 4 sclerosis 6 als 4 sclerosis 8 is 5 ( 6 als 6 als 7 ) 8 is 9 as 9 as 15 disorder 10 an 15 disorder 11 adult 15 disorder 13 onset 15 disorder 14 neurodegenerative 15 disorder 15 disorder 16 involving 16 involving 19 and 17 both 19 and 18 upper 19 and 19 and 21 motor 20 lower 21 motor about 5 % of all cases exhibit signs of frontotemporal degeneration ( ftd ) . 0 ###LEFT-WALL### 3 % 0 ###LEFT-WALL### 7 exhibit 0 ###LEFT-WALL### 15 . 1 about 2 5 2 5 3 % 3 % 4 of 3 % 7 exhibit 4 of 6 cases 5 all 6 cases 7 exhibit 8 signs 8 signs 9 of 9 of 11 degeneration 10 frontotemporal 11 degeneration 11 degeneration 13 ftd 12 ( 13 ftd 13 ftd 14 ) we established the mutation frequency of c9orf72 , sod1 , tardbp , and fus genes in 307 patients with sporadic als , 46 patients with familial als ( fals ) , and 73 patients affected with ftd , all originating from the northeastern part of italy . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 established 0 ###LEFT-WALL### 8 , 1 we 2 established 2 established 5 frequency 3 the 5 frequency 4 mutation 5 frequency 5 frequency 6 of 6 of 7 c9orf72 8 , 32 and 9 sod1 10 , 10 , 11 tardbp 10 , 13 and 12 , 13 and 13 and 15 genes 13 and 16 in 13 and 19 with 13 and 24 patients 13 and 32 and 14 fus 15 genes 16 in 18 patients 17 307 18 patients 19 with 21 als 20 sporadic 21 als 22 , 24 patients 23 46 24 patients 24 patients 25 with 24 patients 31 , 25 with 29 fals 26 familial 29 fals 27 als 29 fals 28 ( 29 fals 29 fals 30 ) 31 , 32 and 32 and 34 patients 32 and 35 affected 32 and 36 with 32 and 40 originating 33 73 34 patients 36 with 37 ftd 38 , 40 originating 39 all 40 originating 40 originating 41 from 40 originating 47 . 41 from 46 italy 42 the 44 part 43 northeastern 44 part 44 part 45 of 44 part 46 italy 45 of 46 italy c9orf72 pathogenic expansion was found on 22 % of familial als , 5 % of sporadic als , [and] 14 % of ftd patients , resulting the most frequently genetic determinant in our cohort . 0 ###LEFT-WALL### 1 c9orf72 0 ###LEFT-WALL### 5 found 0 ###LEFT-WALL### 35 . 1 c9orf72 3 expansion 1 c9orf72 4 was 1 c9orf72 5 found 2 pathogenic 3 expansion 3 expansion 4 was 5 found 6 on 5 found 31 determinant 6 on 8 % 7 22 8 % 8 % 9 of 9 of 11 als 10 familial 11 als 11 als 26 resulting 12 , 26 resulting 13 5 14 % 14 % 15 of 14 % 26 resulting 15 of 17 als 16 sporadic 17 als 17 als 21 % 18 , 21 % 20 14 21 % 21 % 22 of 21 % 25 , 22 of 24 patients 23 ftd 24 patients 27 the 31 determinant 28 most 29 frequently 29 frequently 30 genetic 30 genetic 31 determinant 31 determinant 32 in 32 in 34 cohort 33 our 34 cohort sequence analysis of als cohort [identified] 2 novel [variants] on sod1 ( p.glu41gly ) and fus ( p.gly496glyfs*31 ) . 0 ###LEFT-WALL### 15 and 0 ###LEFT-WALL### 20 . 1 sequence 2 analysis 2 analysis 3 of 2 analysis 15 and 3 of 5 cohort 4 als 5 cohort 5 cohort 7 2 5 cohort 8 novel 8 novel 10 on 8 novel 13 p.glu41gly 10 on 11 sod1 12 ( 13 p.glu41gly 13 p.glu41gly 14 ) 15 and 16 fus 16 fus 18 p.gly496glyfs*31 17 ( 18 p.gly496glyfs*31 18 p.gly496glyfs*31 19 ) interestingly , the single base deletion on fus was observed in an homozygous state , suggesting a recessive pattern of inheritance . 0 ###LEFT-WALL### 6 deletion 0 ###LEFT-WALL### 10 observed 1 interestingly 2 , 1 interestingly 6 deletion 3 the 6 deletion 4 single 6 deletion 5 base 6 deletion 6 deletion 7 on 6 deletion 9 was 7 on 8 fus 9 was 10 observed 10 observed 11 in 11 in 14 state 12 an 14 state 13 homozygous 14 state 14 state 16 suggesting 15 , 16 suggesting 16 suggesting 19 pattern 16 suggesting 22 . 17 a 18 recessive 17 a 19 pattern 18 recessive 19 pattern 19 pattern 20 of 20 of 21 inheritance no point mutations were identified on ftd [cohort] . 0 ###LEFT-WALL### 3 mutations 0 ###LEFT-WALL### 5 identified 0 ###LEFT-WALL### 9 . 1 no 3 mutations 2 point 3 mutations 3 mutations 4 were 4 were 5 identified 5 identified 6 on 6 on 7 ftd although [useful] to direct genetic testing , this study results expand the current knowledge of als genetics . 0 ###LEFT-WALL### 11 expand 0 ###LEFT-WALL### 18 . 1 although 9 study 1 although 10 results 1 although 11 expand 3 to 6 testing 3 to 7 , 3 to 9 study 4 direct 6 testing 5 genetic 6 testing 8 this 9 study 9 study 10 results 11 expand 14 knowledge 12 the 14 knowledge 13 current 14 knowledge 14 knowledge 15 of 15 of 17 genetics 16 als 17 genetics we examine the influence of family processes and acculturation for gender differences in alcohol and drug use among a sample representative of the hispanic population in miami - dade county , florida ( n = 734 ) . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 examine 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 38 . 1 we 2 examine 2 examine 4 influence 3 the 4 influence 4 influence 5 of 5 of 7 processes 6 family 7 processes 8 and 15 and 8 and 17 use 9 acculturation 10 for 9 acculturation 15 and 10 for 12 differences 11 gender 12 differences 12 differences 13 in 13 in 14 alcohol 15 and 16 drug 15 and 17 use 17 use 18 among 17 use 25 population 17 use 26 in 18 among 21 representative 19 a 21 representative 20 sample 21 representative 21 representative 22 of 22 of 24 hispanic 23 the 24 hispanic 26 in 27 miami 27 miami 30 county 28 - 30 county 29 dade 30 county 30 county 32 florida 30 county 37 ) 31 , 32 florida 32 florida 35 = 32 florida 37 ) 33 ( 35 = 34 n 35 = 35 = 36 734 35 = 37 ) we found that [(] a [ )( in age at marriage and acculturation were associated with greater substance use [,] [(] [b] [ )(the associations between age at marriage , acculturation , and substance use were found to be greater for hispanic women [than] men , and [(] [c] [ )(with each additional child born , hispanic women are increasingly less likely to use substances than hispanic men . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 found 1 we 2 found 2 found 3 that 3 that 12 and 3 that 15 associated 5 a 8 in 8 in 9 age 9 age 10 at 9 age 12 and 10 at 11 marriage 12 and 13 acculturation 12 and 14 were 14 were 15 associated 15 associated 16 with 15 associated 26 between 16 with 19 use 16 with 25 associations 17 greater 19 use 18 substance 19 use 24 )(the 25 associations 26 between 33 and 27 age 28 at 27 age 33 and 28 at 29 marriage 29 marriage 31 acculturation 30 , 31 acculturation 31 acculturation 32 , 33 and 34 substance 33 and 35 use 33 and 37 found 35 use 36 were 36 were 37 found 37 found 38 to 38 to 39 be 39 be 40 greater 40 greater 47 and 41 for 45 men 41 for 47 and 42 hispanic 43 women 43 women 45 men 46 , 47 and 47 and 51 )(with 51 )(with 54 child 52 each 54 child 53 additional 54 child 54 child 55 born 54 child 57 hispanic 56 , 57 hispanic 57 hispanic 58 women 57 hispanic 59 are 57 hispanic 69 . 58 women 59 are 59 are 63 to 59 are 66 than 60 increasingly 63 to 61 less 62 likely 62 likely 63 to 63 to 64 use 64 use 65 substances 66 than 68 men 67 hispanic 68 men data reveal that family processes and acculturation jointly impact substance use . ehsp72 ( extracellular heat - shock protein 72 ) is increased in the plasma of both types of diabetes and is positively correlated with inflammatory markers . 0 ###LEFT-WALL### 1 data 0 ###LEFT-WALL### 2 reveal 0 ###LEFT-WALL### 12 . 1 data 2 reveal 2 reveal 3 that 3 that 6 and 3 that 9 impact 4 family 5 processes 5 processes 6 and 6 and 7 acculturation 6 and 9 impact 8 jointly 9 impact 9 impact 11 use 10 substance 11 use 12 . 13 ehsp72 12 . 32 and 12 . 39 . 13 ehsp72 16 heat 13 ehsp72 19 protein 13 ehsp72 32 and 14 ( 16 heat 15 extracellular 16 heat 16 heat 17 - 17 - 19 protein 18 shock 19 protein 19 protein 20 72 19 protein 21 ) 22 is 23 increased 22 is 32 and 23 increased 24 in 24 in 26 plasma 25 the 26 plasma 26 plasma 27 of 27 of 31 diabetes 28 both 29 types 29 types 30 of 29 types 31 diabetes 30 of 31 diabetes 32 and 33 is 33 is 35 correlated 34 positively 35 correlated 35 correlated 36 with 36 with 38 markers 37 inflammatory 38 markers since aging is associated with a low - grade inflammation and ir ( insulin resistance ) , [we] aimed to : [(] [i] [ )(analyse the concentration of ehsp72 in elderly people and determine correlation with insulin resistance , and [(] ii ) determine the effects of ehsp72 on β - cell function and viability in human and rodent pancreatic β - cells . 1 since 2 aging 1 since 4 associated 1 since 8 - 1 since 9 grade 2 aging 3 is 3 is 4 associated 4 associated 5 with 5 with 7 low 6 a 7 low 9 grade 11 and 9 grade 20 to 9 grade 21 : 10 inflammation 11 and 11 and 12 ir 11 and 17 , 11 and 19 aimed 12 ir 15 resistance 13 ( 15 resistance 14 insulin 15 resistance 15 resistance 16 ) 19 aimed 20 to 21 : 33 and 25 )(analyse 27 concentration 25 )(analyse 30 in 25 )(analyse 33 and 26 the 27 concentration 27 concentration 28 of 28 of 29 ehsp72 30 in 32 people 31 elderly 32 people 33 and 34 determine 33 and 35 correlation 35 correlation 36 with 35 correlation 40 and 35 correlation 44 determine 36 with 37 insulin 38 resistance 40 and 39 , 40 and 40 and 42 ii 40 and 43 ) 40 and 44 determine 44 determine 46 effects 44 determine 49 on 44 determine 56 in 45 the 46 effects 46 effects 47 of 47 of 48 ehsp72 49 on 54 and 50 β 51 - 50 β 53 function 52 cell 53 function 53 function 54 and 54 and 55 viability 56 in 58 and 57 human 58 and 58 and 63 cells 58 and 64 . 59 rodent 63 cells 60 pancreatic 63 cells 61 β 62 - 61 β 63 cells fasting blood samples were collected from 50 older people [ 27 females and 23 males ; 63.4±4.4 years of age [;] bmi ( body mass index )=25.5±2.7 [kg/m2] ] . 0 ###LEFT-WALL### 1 fasting 0 ###LEFT-WALL### 4 were 0 ###LEFT-WALL### 16 ; 0 ###LEFT-WALL### 17 63.4±4.4 0 ###LEFT-WALL### 30 . 1 fasting 4 were 2 blood 3 samples 3 samples 4 were 4 were 5 collected 5 collected 6 from 6 from 9 people 7 50 9 people 8 older 9 people 9 people 13 and 10 [ 13 and 11 27 12 females 12 females 13 and 13 and 15 males 13 and 16 ; 14 23 15 males 16 ; 17 63.4±4.4 17 63.4±4.4 18 years 18 years 19 of 18 years 27 )=25.5±2.7 19 of 22 bmi 20 age 22 bmi 23 ( 27 )=25.5±2.7 24 body 27 )=25.5±2.7 25 mass 27 )=25.5±2.7 26 index 27 )=25.5±2.7 27 )=25.5±2.7 29 ] plasma samples were analysed for ehsp72 , insulin , tnf ( tumour necrosis [factor] ) - α , leptin , adiponectin and cortisol , and glycaemic and lipid profile . 0 ###LEFT-WALL### 2 samples 0 ###LEFT-WALL### 4 analysed 0 ###LEFT-WALL### 16 - 1 plasma 2 samples 2 samples 3 were 3 were 4 analysed 4 analysed 5 for 5 for 6 ehsp72 6 ehsp72 8 insulin 6 ehsp72 10 tnf 7 , 8 insulin 8 insulin 9 , 9 , 10 tnf 10 tnf 13 necrosis 10 tnf 16 - 11 ( 13 necrosis 12 tumour 13 necrosis 13 necrosis 15 ) 16 - 27 and 16 - 30 . 17 α 18 , 17 α 19 leptin 19 leptin 20 , 20 , 21 adiponectin 20 , 22 and 22 and 23 cortisol 22 and 24 , 22 and 25 and 25 and 26 glycaemic 25 and 27 and 27 and 29 profile 28 lipid 29 profile in vitro studies were conducted using rodent islets and clonal rat and human pancreatic β - cell lines ( brin - bd11 and 1.1b4 [respectively] ) . 0 ###LEFT-WALL### 3 studies 0 ###LEFT-WALL### 5 conducted 0 ###LEFT-WALL### 27 . 1 in 2 vitro 2 vitro 3 studies 3 studies 4 were 4 were 5 conducted 5 conducted 6 using 6 using 12 and 7 rodent 8 islets 8 islets 9 and 9 and 11 rat 9 and 12 and 10 clonal 11 rat 12 and 15 β 12 and 18 lines 12 and 23 and 13 human 15 β 14 pancreatic 15 β 16 - 18 lines 17 cell 18 lines 18 lines 20 brin 18 lines 21 - 19 ( 20 brin 20 brin 21 - 21 - 23 and 22 bd11 23 and 23 and 24 1.1b4 23 and 26 ) cells/islets were incubated for 24 h with ehsp72 ( 0 , 0.2 , 4 , 8 and 40 ng/ml ) . 0 ###LEFT-WALL### 1 cells/islets 0 ###LEFT-WALL### 3 incubated 0 ###LEFT-WALL### 21 . 1 cells/islets 2 were 2 were 3 incubated 3 incubated 4 for 3 incubated 7 with 4 for 6 h 5 24 6 h 7 with 8 ehsp72 8 ehsp72 10 0 9 ( 10 0 10 0 12 0.2 10 0 14 4 10 0 19 ng/ml 10 0 20 ) 11 , 12 0.2 12 0.2 13 , 13 , 14 4 14 4 15 , 15 , 19 ng/ml 16 8 17 and 17 and 18 40 17 and 19 ng/ml 19 ng/ml 20 ) cell viability was measured using three different methods . 0 ###LEFT-WALL### 2 viability 0 ###LEFT-WALL### 3 was 0 ###LEFT-WALL### 9 . 1 cell 2 viability 2 viability 3 was 3 was 4 measured 4 measured 5 using 5 using 8 methods 6 three 8 methods 7 different 8 methods the impact of hsp72 on β - cell metabolic status was determined using seahorse bioscience xfe96 technology . 0 ###LEFT-WALL### 2 impact 0 ###LEFT-WALL### 11 was 0 ###LEFT-WALL### 18 . 1 the 2 impact 2 impact 3 of 2 impact 11 was 3 of 4 hsp72 4 hsp72 5 on 5 on 10 status 6 β 7 - 6 β 8 cell 8 cell 10 status 9 metabolic 10 status 11 was 12 determined 12 determined 13 using 13 using 17 technology 14 seahorse 15 bioscience 15 bioscience 16 xfe96 16 xfe96 17 technology to assess whether the effects of ehsp72 were mediated by toll - like receptors ( tlr2/tlr4 ) , we co - incubated rodent islets with ehsp72 and the tlr2/tlr4 inhibitor oxpapc ( oxidized 1 - palmitoyl - 2 - arachidonoyl - sn - glycero - 3 - phosphocholine [;] 30 μg / [ml] ) . 0 ###LEFT-WALL### 1 to 0 ###LEFT-WALL### 2 assess 0 ###LEFT-WALL### 12 - 1 to 2 assess 2 assess 3 whether 2 assess 10 by 3 whether 5 effects 3 whether 9 mediated 4 the 5 effects 5 effects 6 of 5 effects 8 were 6 of 7 ehsp72 8 were 9 mediated 10 by 11 toll 12 - 19 we 12 - 20 co 12 - 21 - 13 like 14 receptors 13 like 18 , 13 like 19 we 14 receptors 16 tlr2/tlr4 15 ( 16 tlr2/tlr4 16 tlr2/tlr4 17 ) 19 we 20 co 21 - 23 rodent 21 - 24 islets 22 incubated 23 rodent 23 rodent 24 islets 24 islets 25 with 25 with 27 and 25 with 34 1 26 ehsp72 27 and 27 and 31 oxpapc 27 and 33 oxidized 28 the 30 inhibitor 29 tlr2/tlr4 30 inhibitor 30 inhibitor 31 oxpapc 32 ( 33 oxidized 34 1 36 palmitoyl 34 1 39 - 34 1 43 - 35 - 36 palmitoyl 36 palmitoyl 37 - 37 - 39 - 38 2 39 - 39 - 40 arachidonoyl 39 - 41 - 41 - 43 - 42 sn 43 - 43 - 44 glycero 43 - 55 . 44 glycero 46 3 45 - 46 3 46 3 52 / 46 3 54 ) 47 - 52 / 48 phosphocholine 52 / 50 30 51 μg 51 μg 52 / 52 / 54 ) we found a positive correlation between plasma ehsp72 and homa - ir ( homoeostasis model assessment of ir ) ( r=0.528 , p<0.001 ) , tnf - α ( r=0.389 , p<0.014 ) , cortisol ( r=0.348 , p<0.03 ) and leptin/adiponectin ( r=0.334 , p<0.03 ) . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 found 0 ###LEFT-WALL### 48 . 1 we 2 found 2 found 5 correlation 2 found 41 and 3 a 4 positive 3 a 5 correlation 4 positive 5 correlation 5 correlation 6 between 6 between 7 plasma 8 ehsp72 9 and 9 and 10 homa 9 and 12 ir 9 and 21 r=0.528 9 and 41 and 11 - 12 ir 12 ir 16 assessment 12 ir 19 ) 13 ( 16 assessment 14 homoeostasis 15 model 15 model 16 assessment 16 assessment 17 of 16 assessment 19 ) 17 of 18 ir 20 ( 21 r=0.528 21 r=0.528 23 p<0.001 21 r=0.528 26 tnf 21 r=0.528 40 ) 22 , 23 p<0.001 23 p<0.001 24 ) 25 , 26 tnf 26 tnf 28 α 26 tnf 35 cortisol 26 tnf 40 ) 27 - 28 α 28 α 30 r=0.389 28 α 33 ) 29 ( 30 r=0.389 30 r=0.389 32 p<0.014 30 r=0.389 33 ) 31 , 32 p<0.014 32 p<0.014 33 ) 34 , 35 cortisol 35 cortisol 37 r=0.348 35 cortisol 40 ) 36 ( 37 r=0.348 37 r=0.348 39 p<0.03 37 r=0.348 40 ) 38 , 39 p<0.03 39 p<0.03 40 ) 41 and 42 leptin/adiponectin 41 and 44 r=0.334 43 ( 44 r=0.334 44 r=0.334 46 p<0.03 44 r=0.334 47 ) 45 , 46 p<0.03 46 p<0.03 47 ) in [the] in vitro studies , insulin secretion was decreased in an ehsp72 dose - dependent manner in brin - bd11 cells [(] from 257.7±33 to 84.1±10.2 [μg] / [mg] of protein per 24 h with 40 ng/ml ehsp72 [ )(, and in islets in the presence of 40 ng/ml ehsp72 ( from 0.48±0.07 to 0.33±0.009 μg/20 islets per 24 h [ )( 0 ###LEFT-WALL### 1 in 0 ###LEFT-WALL### 5 studies 0 ###LEFT-WALL### 6 , 1 in 5 studies 3 in 4 vitro 4 vitro 5 studies 6 , 8 secretion 6 , 15 - 7 insulin 8 secretion 8 secretion 9 was 9 was 10 decreased 10 decreased 11 in 11 in 14 dose 12 an 14 dose 13 ehsp72 14 dose 15 - 17 manner 15 - 20 - 16 dependent 17 manner 17 manner 18 in 18 in 19 brin 20 - 21 bd11 21 bd11 22 cells 21 bd11 29 / 21 bd11 31 of 22 cells 24 from 22 cells 26 to 22 cells 27 84.1±10.2 22 cells 29 / 24 from 25 257.7±33 26 to 27 84.1±10.2 31 of 32 protein 32 protein 33 per 33 per 35 h 34 24 35 h 35 h 42 and 36 with 39 ehsp72 36 with 42 and 37 40 38 ng/ml 38 ng/ml 39 ehsp72 41 )(, 42 and 42 and 43 in 43 in 44 islets 44 islets 45 in 44 islets 48 of 45 in 47 presence 46 the 47 presence 48 of 51 ehsp72 49 40 50 ng/ml 50 ng/ml 51 ehsp72 51 ehsp72 53 from 52 ( 53 from 53 from 54 0.48±0.07 53 from 63 )( 54 0.48±0.07 55 to 55 to 58 islets 56 0.33±0.009 58 islets 57 μg/20 58 islets 58 islets 59 per 59 per 61 h 60 24 61 h similarly , ehsp72 reduced β - cell viability ( at least 30 % for brin - bd11 and 10 % [for] 1.1b4 cells ) . 0 ###LEFT-WALL### 3 ehsp72 0 ###LEFT-WALL### 4 reduced 0 ###LEFT-WALL### 25 . 1 similarly 2 , 1 similarly 3 ehsp72 3 ehsp72 4 reduced 4 reduced 8 viability 5 β 6 - 5 β 7 cell 7 cell 8 viability 8 viability 13 % 9 ( 13 % 10 at 11 least 11 least 12 30 12 30 13 % 13 % 14 for 13 % 24 ) 14 for 15 brin 15 brin 23 cells 16 - 23 cells 17 bd11 18 and 18 and 22 1.1b4 18 and 23 cells 19 10 20 % 20 % 22 1.1b4 23 cells 24 ) bioenergetic studies revealed that ehsp72 altered pancreatic β - cell metabolism . 0 ###LEFT-WALL### 1 bioenergetic 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 12 . 1 bioenergetic 2 studies 2 studies 11 metabolism 3 revealed 10 cell 4 that 5 ehsp72 5 ehsp72 10 cell 6 altered 10 cell 7 pancreatic 10 cell 8 β 9 - 8 β 10 cell 10 cell 11 metabolism oxpapc restored insulin secretion in islets incubated with 40 ng/ml ehsp72 . 0 ###LEFT-WALL### 1 oxpapc 0 ###LEFT-WALL### 2 restored 0 ###LEFT-WALL### 12 . 1 oxpapc 2 restored 2 restored 4 secretion 2 restored 5 in 2 restored 8 with 3 insulin 4 secretion 5 in 6 islets 6 islets 7 incubated 8 with 11 ehsp72 9 40 10 ng/ml 10 ng/ml 11 ehsp72 in conclusion , we have demonstrated a positive correlation between ehsp72 and ir . 0 ###LEFT-WALL### 2 conclusion 0 ###LEFT-WALL### 3 , 0 ###LEFT-WALL### 14 . 1 in 2 conclusion 3 , 4 we 3 , 6 demonstrated 4 we 5 have 5 have 6 demonstrated 6 demonstrated 9 correlation 6 demonstrated 10 between 7 a 8 positive 7 a 9 correlation 8 positive 9 correlation 10 between 12 and 11 ehsp72 12 and 12 and 13 ir in addition , we suggest that chronic ehsp72 exposure may mediate β - cell failure . 0 ###LEFT-WALL### 4 we 0 ###LEFT-WALL### 5 suggest 0 ###LEFT-WALL### 16 . 1 in 2 addition 1 in 3 , 1 in 4 we 4 we 5 suggest 5 suggest 6 that 6 that 9 exposure 6 that 11 mediate 7 chronic 9 exposure 8 ehsp72 9 exposure 9 exposure 10 may 10 may 11 mediate 11 mediate 15 failure 12 β 13 - 12 β 14 cell 14 cell 15 failure objective : the worldwide population aging and the nowadays medical advances [impose] to consider new management guidelines [for] elderly . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 20 . 1 objective 2 : 2 : 7 and 2 : 13 to 3 the 7 and 4 worldwide 5 population 5 population 6 aging 5 population 7 and 7 and 11 advances 8 the 11 advances 9 nowadays 10 medical 10 medical 11 advances 13 to 14 consider 14 consider 17 guidelines 14 consider 19 elderly 15 new 16 management 16 management 17 guidelines aim of this study was to assess the best treatment [in] elderly with multiple intracranial aneurysms ( mia ) . 0 ###LEFT-WALL### 1 aim 0 ###LEFT-WALL### 5 was 0 ###LEFT-WALL### 20 . 1 aim 2 of 1 aim 5 was 2 of 4 study 3 this 4 study 5 was 6 to 5 was 12 elderly 6 to 7 assess 7 assess 10 treatment 8 the 9 best 8 the 10 treatment 12 elderly 13 with 13 with 16 aneurysms 14 multiple 16 aneurysms 15 intracranial 16 aneurysms 16 aneurysms 18 mia 17 ( 18 mia 18 mia 19 ) methods : from 1994 to 2011 , we admitted 1462 patients with ruptured cerebral aneurysm . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 7 , 0 ###LEFT-WALL### 16 . 1 methods 2 : 2 : 3 from 3 from 5 to 4 1994 5 to 5 to 6 2011 7 , 8 we 7 , 9 admitted 8 we 9 admitted 9 admitted 11 patients 9 admitted 12 with 10 1462 11 patients 12 with 15 aneurysm 13 ruptured 15 aneurysm 14 cerebral 15 aneurysm among those aged ≥65 years , 43 had mia ( 15 % [of] [elderly] ) . 0 ###LEFT-WALL### 7 43 0 ###LEFT-WALL### 8 had 0 ###LEFT-WALL### 16 . 1 among 5 years 1 among 6 , 1 among 7 43 2 those 5 years 3 aged 5 years 4 ≥65 5 years 7 43 8 had 8 had 9 mia 9 mia 12 % 10 ( 12 % 11 15 12 % 12 % 15 ) size and aneurysm location , timing and type of treatment were analyzed . 0 ###LEFT-WALL### 7 and 0 ###LEFT-WALL### 12 analyzed 0 ###LEFT-WALL### 13 . 1 size 2 and 2 and 4 location 2 and 5 , 3 aneurysm 4 location 5 , 6 timing 5 , 7 and 7 and 8 type 7 and 9 of 7 and 11 were 9 of 10 treatment 11 were 12 analyzed patients were thus stratified according to hunt [-] hess grade on admission and evaluated at 6 months using the glasgow outcome scale ( gos ) . 0 ###LEFT-WALL### 1 patients 0 ###LEFT-WALL### 2 were 0 ###LEFT-WALL### 26 . 1 patients 2 were 2 were 13 and 3 thus 4 stratified 4 stratified 6 to 4 stratified 10 grade 4 stratified 11 on 4 stratified 13 and 5 according 6 to 6 to 9 hess 7 hunt 9 hess 11 on 12 admission 13 and 14 evaluated 14 evaluated 15 at 14 evaluated 18 using 14 evaluated 22 scale 15 at 17 months 16 6 17 months 18 using 21 outcome 19 the 21 outcome 20 glasgow 21 outcome 22 scale 24 gos 23 ( 24 gos 24 gos 25 ) results : we had 87 aneurysms in the final series . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 3 we 2 : 4 had 2 : 11 . 3 we 4 had 4 had 6 aneurysms 4 had 7 in 5 87 6 aneurysms 7 in 10 series 8 the 10 series 9 final 10 series three patients died because of the impossibility to treat the ruptured aneurysm . 0 ###LEFT-WALL### 2 patients 0 ###LEFT-WALL### 3 died 0 ###LEFT-WALL### 13 . 1 three 2 patients 2 patients 3 died 3 died 4 because 4 because 5 of 5 of 7 impossibility 6 the 7 impossibility 7 impossibility 8 to 7 impossibility 9 treat 8 to 9 treat 9 treat 12 aneurysm 10 the 12 aneurysm 11 ruptured 12 aneurysm no new bleeding from untreated aneurysms was observed ; no retreatment after previous coiling was performed . 0 ###LEFT-WALL### 3 bleeding 0 ###LEFT-WALL### 8 observed 0 ###LEFT-WALL### 9 ; 0 ###LEFT-WALL### 11 retreatment 0 ###LEFT-WALL### 17 . 1 no 3 bleeding 2 new 3 bleeding 3 bleeding 4 from 3 bleeding 7 was 4 from 6 aneurysms 5 untreated 6 aneurysms 7 was 8 observed 9 ; 10 no 10 no 11 retreatment 11 retreatment 12 after 12 after 14 coiling 12 after 16 performed 13 previous 14 coiling 14 coiling 15 was 15 was 16 performed conclusions : mia lead to significantly poorer outcomes , especially [in] elderly , because of their general clinical condition , presence of risk factors and lower capacity of reaction to stressful events . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 33 . 2 : 3 mia 2 : 4 lead 3 mia 4 lead 4 lead 5 to 4 lead 14 because 5 to 8 outcomes 6 significantly 7 poorer 7 poorer 8 outcomes 8 outcomes 12 elderly 9 , 12 elderly 10 especially 12 elderly 12 elderly 13 , 14 because 15 of 15 of 27 capacity 16 their 27 capacity 17 general 27 capacity 18 clinical 27 capacity 19 condition 20 , 20 , 21 presence 20 , 25 and 21 presence 22 of 22 of 24 factors 23 risk 24 factors 25 and 26 lower 25 and 27 capacity 27 capacity 28 of 28 of 29 reaction 29 reaction 30 to 30 to 32 events 31 stressful 32 events in patients without large hematomas , coiling of the ruptured aneurysm represents the procedure with high effectiveness . 0 ###LEFT-WALL### 7 coiling 0 ###LEFT-WALL### 12 represents 0 ###LEFT-WALL### 18 . 1 in 2 patients 1 in 6 , 1 in 7 coiling 2 patients 3 without 3 without 5 hematomas 4 large 5 hematomas 7 coiling 8 of 7 coiling 12 represents 8 of 11 aneurysm 9 the 11 aneurysm 10 ruptured 11 aneurysm 12 represents 14 procedure 12 represents 15 with 13 the 14 procedure 15 with 17 effectiveness 16 high 17 effectiveness the clinical conditions on admission represent the most important factor for the treatment results . 0 ###LEFT-WALL### 3 conditions 0 ###LEFT-WALL### 6 represent 0 ###LEFT-WALL### 15 . 1 the 3 conditions 2 clinical 3 conditions 3 conditions 4 on 3 conditions 6 represent 4 on 5 admission 6 represent 10 factor 7 the 10 factor 8 most 9 important 9 important 10 factor 10 factor 11 for 11 for 14 results 12 the 14 results 13 treatment 14 results to reduce the treatment - related risks we do recommend a conservative approach for the unruptured aneurysms . 0 ###LEFT-WALL### 1 to 0 ###LEFT-WALL### 2 reduce 0 ###LEFT-WALL### 6 related 1 to 2 reduce 2 reduce 4 treatment 3 the 4 treatment 5 - 6 related 6 related 7 risks 6 related 18 . 7 risks 8 we 7 risks 13 approach 8 we 9 do 9 do 10 recommend 10 recommend 12 conservative 10 recommend 13 approach 11 a 12 conservative 13 approach 14 for 14 for 17 aneurysms 15 the 17 aneurysms 16 unruptured 17 aneurysms background and aim : liver regeneration likely decreases with age by [an] , as yet , incompletely understood [mechanism] , restricting the extent of hepatectomy . 0 ###LEFT-WALL### 3 aim 0 ###LEFT-WALL### 4 : 1 background 2 and 2 and 3 aim 3 aim 4 : 4 : 5 liver 5 liver 6 regeneration 5 liver 11 by 5 liver 15 yet 5 liver 18 understood 5 liver 21 restricting 6 regeneration 8 decreases 7 likely 8 decreases 8 decreases 9 with 8 decreases 11 by 9 with 10 age 13 , 15 yet 14 as 15 yet 15 yet 16 , 16 , 18 understood 17 incompletely 18 understood 18 understood 20 , 20 , 21 restricting 21 restricting 23 extent 21 restricting 26 . 22 the 23 extent 23 extent 24 of 24 of 25 hepatectomy we therefore analyzed the effect of aging on liver regeneration and investigated mechanisms associate with poor regeneration of human liver . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 analyzed 0 ###LEFT-WALL### 21 . 1 we 3 analyzed 2 therefore 3 analyzed 3 analyzed 11 and 3 analyzed 14 associate 4 the 5 effect 5 effect 6 of 5 effect 11 and 6 of 7 aging 7 aging 8 on 8 on 10 regeneration 9 liver 10 regeneration 11 and 13 mechanisms 11 and 14 associate 12 investigated 13 mechanisms 14 associate 15 with 15 with 17 regeneration 16 poor 17 regeneration 17 regeneration 18 of 18 of 20 liver 19 human 20 liver methods : we assessed 130 patients who underwent hepatectomy at our institute between 2005 and 2012 . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 3 we 2 : 4 assessed 2 : 17 . 3 we 4 assessed 4 assessed 6 patients 5 130 6 patients 6 patients 7 who 6 patients 8 underwent 7 who 8 underwent 8 underwent 9 hepatectomy 8 underwent 10 at 8 underwent 13 between 10 at 12 institute 11 our 12 institute 13 between 15 and 14 2005 15 and 15 and 16 2012 the patients were divided into two groups , a younger [(] age < 65 years , n = 59 ) and an older [(] age > 65 years , n = 71 ) group . 0 ###LEFT-WALL### 2 patients 0 ###LEFT-WALL### 4 divided 0 ###LEFT-WALL### 8 , 0 ###LEFT-WALL### 35 . 1 the 2 patients 2 patients 3 were 3 were 4 divided 4 divided 5 into 5 into 7 groups 6 two 7 groups 8 , 12 age 8 , 13 < 9 a 12 age 10 younger 12 age 12 age 13 < 13 < 21 and 14 65 21 and 15 years 18 = 15 years 21 and 16 , 18 = 17 n 18 = 18 = 19 59 18 = 20 ) 21 and 25 age 21 and 28 years 21 and 34 group 22 an 25 age 23 older 25 age 26 > 27 65 27 65 28 years 28 years 31 = 28 years 34 group 29 , 31 = 30 n 31 = 31 = 32 71 31 = 33 ) the expression of hepatocyte growth [factor] ( hgf ) , its [ligand] met , and the senescence - related genes p16 , sirt1 and smp30 were assessed by qrt - pcr . 0 ###LEFT-WALL### 15 and 0 ###LEFT-WALL### 21 p16 0 ###LEFT-WALL### 22 , 0 ###LEFT-WALL### 32 . 1 the 2 expression 2 expression 3 of 2 expression 15 and 3 of 5 growth 4 hepatocyte 5 growth 5 growth 8 hgf 5 growth 13 met 7 ( 8 hgf 8 hgf 9 ) 10 , 13 met 11 its 13 met 13 met 14 , 15 and 17 senescence 15 and 21 p16 16 the 17 senescence 18 - 19 related 19 related 20 genes 19 related 21 p16 22 , 24 and 22 , 27 assessed 23 sirt1 24 and 24 and 25 smp30 24 and 26 were 26 were 27 assessed 27 assessed 28 by 28 by 31 pcr 29 qrt 30 - 29 qrt 31 pcr simulated preoperative and 1 week and 6 month postoperative liver volumes were evaluated in 11 [younger] and 11 older patients using a 3 d simulation imaging system . 0 ###LEFT-WALL### 1 simulated 0 ###LEFT-WALL### 28 . 1 simulated 12 were 1 simulated 14 in 2 preoperative 3 and 3 and 5 week 3 and 6 and 4 1 5 week 6 and 11 volumes 6 and 12 were 7 6 8 month 8 month 11 volumes 9 postoperative 10 liver 10 liver 11 volumes 12 were 13 evaluated 14 in 20 patients 15 11 17 and 17 and 18 11 17 and 20 patients 19 older 20 patients 20 patients 21 using 21 using 27 system 22 a 27 system 23 3 24 d 24 d 27 system 25 simulation 27 system 26 imaging 27 system regenerated liver volumes were calculated and compared with clinicopathological factors , and correlations between liver regeneration and gene expression were calculated . 0 ###LEFT-WALL### 3 volumes 0 ###LEFT-WALL### 4 were 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 22 . 1 regenerated 2 liver 2 liver 3 volumes 3 volumes 4 were 4 were 6 and 5 calculated 6 and 6 and 7 compared 7 compared 8 with 8 with 10 factors 9 clinicopathological 10 factors 11 , 12 and 12 and 13 correlations 12 and 20 were 13 correlations 14 between 13 correlations 20 were 14 between 17 and 15 liver 16 regeneration 16 regeneration 17 and 17 and 19 expression 18 gene 19 expression 20 were 21 calculated results : hgf and met expression was significantly lower , and p16 expression significantly higher in older than [in] younger patients ( p < 0.05 each ) . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 11 and 2 : 28 . 3 hgf 4 and 4 and 5 met 4 and 6 expression 4 and 9 lower 4 and 11 and 6 expression 7 was 7 was 9 lower 8 significantly 9 lower 10 , 11 and 11 and 13 expression 11 and 27 ) 12 p16 13 expression 13 expression 15 higher 14 significantly 15 higher 15 higher 16 in 15 higher 24 < 15 higher 26 each 16 in 21 patients 17 older 21 patients 18 than 20 younger 20 younger 21 patients 22 ( 24 < 23 p 24 < 24 < 25 0.05 mean increases in liver volume after 6 months were significantly greater in younger than in older patients ( 396.5 ml , 45.6 % vs 159.4 ml , 23.3 % , p < 0.05 ) but did not differ significantly at 1 week . 0 ###LEFT-WALL### 35 but 0 ###LEFT-WALL### 43 . 1 mean 2 increases 1 mean 35 but 2 increases 3 in 2 increases 6 after 2 increases 13 younger 3 in 5 volume 4 liver 5 volume 6 after 7 6 7 6 8 months 7 6 12 in 8 months 9 were 9 were 10 significantly 9 were 11 greater 11 greater 12 in 13 younger 14 than 13 younger 32 < 14 than 15 in 15 in 17 patients 16 older 17 patients 17 patients 20 ml 17 patients 23 % 17 patients 29 % 18 ( 20 ml 19 396.5 20 ml 20 ml 21 , 21 , 23 % 22 45.6 23 % 23 % 24 vs 23 % 27 , 24 vs 26 ml 25 159.4 26 ml 27 , 29 % 28 23.3 29 % 29 % 30 , 30 , 32 < 31 p 32 < 32 < 33 0.05 32 < 34 ) 35 but 36 did 36 did 37 not 36 did 38 differ 38 differ 39 significantly 38 differ 40 at 40 at 42 week 41 1 42 week furthermore , p16 expression was negatively correlated with liver regeneration in older patients ( r = - 0.67 , p < 0.05 ) . 0 ###LEFT-WALL### 4 expression 0 ###LEFT-WALL### 7 correlated 0 ###LEFT-WALL### 24 . 1 furthermore 2 , 1 furthermore 4 expression 3 p16 4 expression 4 expression 5 was 5 was 7 correlated 6 negatively 7 correlated 7 correlated 8 with 7 correlated 16 = 7 correlated 21 < 8 with 10 regeneration 9 liver 10 regeneration 10 regeneration 11 in 11 in 13 patients 12 older 13 patients 14 ( 16 = 15 r 16 = 16 = 17 - 17 - 18 0.67 17 - 21 < 19 , 21 < 20 p 21 < 21 < 22 0.05 21 < 23 ) conclusion : poor liver regeneration in older patients may be associated with the upregulation of senescence - related genes , such as p16 , and the downregulation of regeneration - promoting genes , such as hgf and met . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 18 related 0 ###LEFT-WALL### 39 . 1 conclusion 2 : 2 : 4 liver 3 poor 4 liver 4 liver 5 regeneration 4 liver 10 be 4 liver 11 associated 4 liver 12 with 5 regeneration 6 in 5 regeneration 9 may 6 in 8 patients 7 older 8 patients 9 may 10 be 12 with 14 upregulation 13 the 14 upregulation 14 upregulation 15 of 15 of 16 senescence 17 - 18 related 18 related 19 genes 18 related 35 as 19 genes 22 as 19 genes 31 promoting 20 , 22 as 21 such 22 as 22 as 25 and 22 as 30 - 23 p16 25 and 24 , 25 and 25 and 27 downregulation 25 and 28 of 26 the 27 downregulation 28 of 29 regeneration 30 - 31 promoting 31 promoting 32 genes 31 promoting 33 , 34 such 35 as 35 as 37 and 36 hgf 37 and 37 and 38 met background : primary care physicians routinely provide dementia care , but may lack the clinical skills and awareness of available resources to provide optimal care . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 5 physicians 2 : 11 but 2 : 26 . 3 primary 4 care 4 care 5 physicians 5 physicians 11 but 6 routinely 7 provide 7 provide 9 care 7 provide 11 but 8 dementia 9 care 10 , 11 but 11 but 12 may 12 may 13 lack 13 lack 17 and 13 lack 22 to 14 the 16 skills 15 clinical 16 skills 16 skills 17 and 17 and 18 awareness 17 and 19 of 19 of 21 resources 20 available 21 resources 22 to 23 provide 23 provide 25 care 24 optimal 25 care we conducted a community - based pilot dementia training intervention designed to both improve clinical competency and increase utilization of local dementia care services . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 conducted 0 ###LEFT-WALL### 5 - 0 ###LEFT-WALL### 25 . 1 we 2 conducted 2 conducted 4 community 3 a 4 community 5 - 17 and 6 based 8 dementia 6 based 12 to 6 based 17 and 7 pilot 8 dementia 8 dementia 9 training 9 training 10 intervention 10 intervention 11 designed 12 to 14 improve 13 both 14 improve 14 improve 16 competency 15 clinical 16 competency 17 and 18 increase 18 increase 19 utilization 19 utilization 20 of 20 of 24 services 21 local 23 care 22 dementia 23 care 23 care 24 services methods : physicians ( n = 29 ) and affiliated staff ( n = 24 ) participated in a one [-] day training program on dementia screening , diagnosis and management that included direct engagement with local support service providers . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 33 included 0 ###LEFT-WALL### 41 . 1 methods 2 : 2 : 3 physicians 3 physicians 6 = 4 ( 6 = 5 n 6 = 6 = 7 29 6 = 8 ) 9 and 11 staff 9 and 17 participated 10 affiliated 11 staff 11 staff 14 = 11 staff 17 participated 12 ( 14 = 13 n 14 = 14 = 15 24 14 = 16 ) 17 participated 18 in 17 participated 25 on 18 in 24 program 19 a 24 program 20 one 22 day 22 day 23 training 23 training 24 program 25 on 30 and 26 dementia 27 screening 27 screening 28 , 28 , 29 diagnosis 28 , 30 and 30 and 31 management 30 and 32 that 30 and 33 included 32 that 33 included 33 included 35 engagement 34 direct 35 engagement 35 engagement 36 with 36 with 40 providers 37 local 40 providers 38 support 40 providers 39 service 40 providers questionnaires about their dementia care competency and referral patterns were completed before and 6 months after the training intervention . 0 ###LEFT-WALL### 7 and 0 ###LEFT-WALL### 11 completed 0 ###LEFT-WALL### 20 . 1 questionnaires 2 about 1 questionnaires 7 and 2 about 6 competency 3 their 6 competency 4 dementia 5 care 5 care 6 competency 7 and 9 patterns 7 and 10 were 8 referral 9 patterns 10 were 11 completed 11 completed 13 and 12 before 13 and 13 and 16 after 14 6 15 months 15 months 16 after 16 after 19 intervention 17 the 19 intervention 18 training 19 intervention results : physicians reported significantly higher overall confidence in their dementia care competency 6 months post - training compared to pre - training . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 17 - 1 results 2 : 2 : 8 confidence 3 physicians 4 reported 4 reported 8 confidence 5 significantly 6 higher 6 higher 8 confidence 7 overall 8 confidence 8 confidence 9 in 9 in 16 post 10 their 16 post 11 dementia 16 post 12 care 16 post 13 competency 16 post 14 6 15 months 15 months 16 post 17 - 18 training 17 - 19 compared 17 - 22 - 18 training 19 compared 19 compared 20 to 20 to 21 pre 22 - 23 training 22 - 24 . the largest reported improvements were in their ability to educate patients and caregivers about dementia and making appropriate referrals to community care services . 0 ###LEFT-WALL### 2 largest 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 24 . 1 the 2 largest 2 largest 12 and 3 reported 4 improvements 3 reported 5 were 3 reported 12 and 4 improvements 5 were 5 were 6 in 6 in 8 ability 7 their 8 ability 8 ability 9 to 8 ability 10 educate 9 to 10 educate 10 educate 11 patients 12 and 13 caregivers 12 and 14 about 12 and 20 to 14 about 19 referrals 15 dementia 16 and 16 and 17 making 16 and 19 referrals 18 appropriate 19 referrals 20 to 23 services 21 community 22 care 22 care 23 services participants also reported markedly increased use of cognitive screening tools in providing care . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 5 increased 0 ###LEFT-WALL### 14 . 1 participants 3 reported 1 participants 5 increased 2 also 3 reported 3 reported 4 markedly 5 increased 6 use 5 increased 11 in 6 use 7 of 7 of 10 tools 8 cognitive 10 tools 9 screening 10 tools 11 in 12 providing 12 providing 13 care community service providers recorded approximately 160 physician [-] initiated referrals over a 2 year - period post - training , compared to few beforehand . 0 ###LEFT-WALL### 3 providers 0 ###LEFT-WALL### 4 recorded 0 ###LEFT-WALL### 25 . 1 community 3 providers 2 service 3 providers 3 providers 4 recorded 4 recorded 10 referrals 4 recorded 22 to 4 recorded 24 beforehand 5 approximately 6 160 6 160 10 referrals 7 physician 9 initiated 9 initiated 10 referrals 10 referrals 11 over 10 referrals 21 compared 11 over 14 year 12 a 14 year 13 2 14 year 14 year 17 post 15 - 17 post 16 period 17 post 17 post 19 training 17 post 20 , 18 - 19 training 19 training 20 , 22 to 23 few conclusions : combining a targeted physician practice - based educational intervention with community service engagement improves dementia care competency in clinicians and promotes linkages between clinical and community dementia care providers . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 32 . 2 : 11 intervention 2 : 16 improves 3 combining 7 practice 3 combining 8 - 3 combining 11 intervention 4 a 7 practice 5 targeted 6 physician 6 physician 7 practice 9 based 11 intervention 10 educational 11 intervention 11 intervention 12 with 11 intervention 16 improves 12 with 15 engagement 13 community 14 service 14 service 15 engagement 16 improves 19 competency 17 dementia 19 competency 18 care 19 competency 19 competency 20 in 20 in 22 and 21 clinicians 22 and 22 and 23 promotes 22 and 24 linkages 22 and 25 between 25 between 27 and 26 clinical 27 and 27 and 31 providers 28 community 29 dementia 29 dementia 30 care 30 care 31 providers it has been suggested that intrinsic abilities for regulating emotions remain stable or improve with ageing , but , to date , no studies have examined age - related differences in extrinsic emotion regulation . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 3 been 0 ###LEFT-WALL### 18 but 1 it 2 has 2 has 3 been 3 been 7 abilities 3 been 8 for 4 suggested 7 abilities 5 that 6 intrinsic 6 intrinsic 7 abilities 8 for 9 regulating 9 regulating 10 emotions 9 regulating 13 or 10 emotions 13 or 11 remain 12 stable 11 remain 13 or 13 or 14 improve 14 improve 15 with 15 with 16 ageing 17 , 18 but 18 but 24 studies 18 but 25 have 19 , 21 date 20 to 21 date 21 date 22 , 21 date 24 studies 23 no 24 studies 24 studies 25 have 25 have 27 age 26 examined 27 age 27 age 30 differences 28 - 30 differences 29 related 30 differences 30 differences 31 in 30 differences 35 . 31 in 34 regulation 32 extrinsic 33 emotion 33 emotion 34 regulation since humour has been found to be an effective form of emotion regulation , we used a paradigm similar to that of strick and colleagues ( 2009 ) with two objectives : to compare extrinsic humorous emotion regulation in young and older adults and to test whether the potential beneficial effect of humour on negative emotion is better explained by the cognitive distraction hypothesis or by the positive [affect] elicitation hypothesis . 0 ###LEFT-WALL### 15 we 0 ###LEFT-WALL### 16 used 0 ###LEFT-WALL### 32 : 0 ###LEFT-WALL### 72 . 1 since 2 humour 1 since 5 found 1 since 14 , 1 since 15 we 2 humour 3 has 3 has 4 been 4 been 5 found 5 found 6 to 6 to 7 be 7 be 10 form 8 an 9 effective 8 an 10 form 9 effective 10 form 10 form 11 of 11 of 13 regulation 12 emotion 13 regulation 15 we 16 used 16 used 18 paradigm 17 a 18 paradigm 18 paradigm 19 similar 19 similar 20 to 19 similar 29 with 20 to 24 and 21 that 22 of 21 that 24 and 22 of 23 strick 24 and 25 colleagues 24 and 27 2009 26 ( 27 2009 27 2009 28 ) 29 with 30 two 29 with 31 objectives 32 : 33 to 32 : 44 and 33 to 44 and 34 compare 38 regulation 34 compare 39 in 34 compare 44 and 35 extrinsic 38 regulation 36 humorous 37 emotion 37 emotion 38 regulation 39 in 43 adults 40 young 41 and 41 and 42 older 41 and 43 adults 44 and 45 to 44 and 59 explained 44 and 65 or 45 to 46 test 46 test 47 whether 47 whether 51 effect 47 whether 57 is 48 the 51 effect 49 potential 51 effect 50 beneficial 51 effect 51 effect 52 of 51 effect 57 is 52 of 53 humour 53 humour 54 on 54 on 56 emotion 55 negative 56 emotion 58 better 59 explained 60 by 64 hypothesis 60 by 65 or 61 the 64 hypothesis 62 cognitive 63 distraction 63 distraction 64 hypothesis 65 or 66 by 66 by 71 hypothesis 67 the 71 hypothesis 68 positive 70 elicitation 70 elicitation 71 hypothesis to this end , neutral , [moderately] [,] and strongly negative pictures followed by humorous , simply positive , or weird cartoons , controlled for both their funniness and cognitive demands , were presented to 26 young and 25 older adults with the instruction to [report] their negative feelings . 0 ###LEFT-WALL### 3 end 0 ###LEFT-WALL### 4 , 1 to 2 this 1 to 3 end 4 , 9 and 4 , 16 , 5 neutral 9 and 6 , 9 and 9 and 12 pictures 9 and 13 followed 10 strongly 11 negative 11 negative 12 pictures 13 followed 14 by 13 followed 15 humorous 16 , 22 cartoons 17 simply 22 cartoons 18 positive 20 or 19 , 20 or 20 or 21 weird 20 or 22 cartoons 22 cartoons 24 controlled 22 cartoons 32 , 23 , 24 controlled 24 controlled 25 for 25 for 29 and 26 both 29 and 27 their 28 funniness 28 funniness 29 and 29 and 30 cognitive 31 demands 32 , 32 , 33 were 32 , 38 and 33 were 34 presented 34 presented 35 to 35 to 36 26 37 young 38 and 38 and 41 adults 38 and 50 . 39 25 41 adults 40 older 41 adults 41 adults 42 with 41 adults 45 to 42 with 44 instruction 43 the 44 instruction 45 to 49 feelings 47 their 49 feelings 48 negative 49 feelings when induced to feel moderately negative emotions , both young and older adults reported a lower negative feeling after viewing the humorous cartoons than after the other ones . 0 ###LEFT-WALL### 13 adults 0 ###LEFT-WALL### 14 reported 0 ###LEFT-WALL### 29 . 1 when 2 induced 1 when 8 , 1 when 13 adults 2 induced 3 to 3 to 4 feel 4 feel 7 emotions 5 moderately 6 negative 6 negative 7 emotions 9 both 13 adults 10 young 11 and 11 and 12 older 11 and 13 adults 13 adults 14 reported 14 reported 18 feeling 14 reported 19 after 14 reported 24 than 15 a 18 feeling 16 lower 18 feeling 17 negative 18 feeling 19 after 20 viewing 20 viewing 23 cartoons 21 the 23 cartoons 22 humorous 23 cartoons 24 than 25 after 25 after 28 ones 26 the 27 other 27 other 28 ones this indicates that the extrinsic humorous emotion regulation skill remains stable with ageing and suggests that the beneficial effect of humour on emotional feeling cannot be seen as a purely cognitive distraction . 0 ###LEFT-WALL### 1 this 0 ###LEFT-WALL### 2 indicates 0 ###LEFT-WALL### 33 . 1 this 2 indicates 2 indicates 3 that 3 that 9 skill 3 that 14 and 4 the 9 skill 5 extrinsic 7 emotion 6 humorous 7 emotion 7 emotion 9 skill 8 regulation 9 skill 9 skill 14 and 10 remains 11 stable 10 remains 14 and 11 stable 12 with 12 with 13 ageing 14 and 15 suggests 14 and 28 as 15 suggests 16 that 16 that 19 effect 16 that 27 seen 17 the 19 effect 18 beneficial 19 effect 19 effect 20 of 19 effect 25 cannot 20 of 21 humour 21 humour 22 on 22 on 24 feeling 23 emotional 24 feeling 25 cannot 26 be 26 be 27 seen 28 as 32 distraction 29 a 30 purely 29 a 32 distraction 30 purely 31 cognitive 31 cognitive 32 distraction background : in case of many individuals , decrease of body mass [is] observed [during] aging , that is often in elderly living in nursing homes . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 17 , 0 ###LEFT-WALL### 27 . 1 background 2 : 2 : 5 of 3 in 4 case 4 case 5 of 5 of 7 individuals 6 many 7 individuals 7 individuals 9 decrease 8 , 9 decrease 9 decrease 10 of 9 decrease 17 , 10 of 16 aging 11 body 12 mass 12 mass 14 observed 14 observed 16 aging 17 , 18 that 17 , 19 is 18 that 19 is 19 is 20 often 19 is 21 in 21 in 23 living 22 elderly 23 living 23 living 24 in 24 in 25 nursing 25 nursing 26 homes it is especially important for patients with alzheimer 's disease ( ad ) , when [decrease] of body mass [,] resulting in malnutrition . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 2 is 1 it 2 is 2 is 4 important 3 especially 4 important 4 important 5 for 4 important 7 with 4 important 15 when 5 for 6 patients 7 with 10 disease 8 alzheimer 9 's 9 's 10 disease 10 disease 12 ad 11 ( 12 ad 12 ad 13 ) 14 , 15 when 15 when 17 of 15 when 24 . 17 of 21 resulting 18 body 21 resulting 19 mass 21 resulting 21 resulting 22 in 22 in 23 malnutrition objective : the aim of the study was the assessment of the quality of diet of ad individuals living at homes and [in] nursing homes , in comparison with a control group material and methods : in the study [participated] 160 individuals [with] and without ad , living at home or in nursing homes . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 2 : 4 aim 3 the 4 aim 4 aim 5 of 4 aim 8 was 5 of 7 study 6 the 7 study 8 was 10 assessment 9 the 10 assessment 10 assessment 11 of 11 of 22 and 12 the 13 quality 13 quality 14 of 13 quality 16 of 13 quality 22 and 14 of 15 diet 16 of 19 living 17 ad 19 living 18 individuals 19 living 19 living 20 at 20 at 21 homes 22 and 25 homes 22 and 26 , 22 and 27 in 24 nursing 25 homes 27 in 28 comparison 28 comparison 29 with 29 with 34 and 30 a 31 control 30 a 34 and 31 control 32 group 32 group 33 material 34 and 35 methods 34 and 36 : 35 methods 36 : 36 : 44 and 37 in 42 individuals 37 in 44 and 38 the 42 individuals 39 study 42 individuals 41 160 42 individuals 44 and 45 without 45 without 46 ad 46 ad 48 living 47 , 48 living 48 living 51 or 48 living 55 . 49 at 50 home 49 at 51 or 51 or 52 in 52 in 53 nursing 53 nursing 54 homes assessment of diet [of] individuals living at homes was based on self [-] reported data from one - day dietary recall . 0 ###LEFT-WALL### 1 assessment 0 ###LEFT-WALL### 10 based 0 ###LEFT-WALL### 18 - 0 ###LEFT-WALL### 22 . 1 assessment 2 of 1 assessment 6 living 1 assessment 9 was 2 of 5 individuals 3 diet 5 individuals 6 living 7 at 7 at 8 homes 9 was 10 based 10 based 11 on 11 on 15 data 12 self 14 reported 14 reported 15 data 15 data 16 from 16 from 17 one 18 - 21 recall 19 day 21 recall 20 dietary 21 recall assessment of diet [of] individuals living in nursing homes was based on one [-] day menu from nursing homes accompanied by information about snacking between meals . 0 ###LEFT-WALL### 1 assessment 0 ###LEFT-WALL### 11 based 0 ###LEFT-WALL### 27 . 1 assessment 2 of 1 assessment 6 living 1 assessment 10 was 2 of 5 individuals 3 diet 5 individuals 6 living 7 in 7 in 8 nursing 8 nursing 9 homes 10 was 11 based 11 based 12 on 11 based 17 from 11 based 23 about 12 on 16 menu 13 one 16 menu 15 day 16 menu 17 from 18 nursing 18 nursing 19 homes 18 nursing 21 by 19 homes 20 accompanied 21 by 22 information 23 about 24 snacking 24 snacking 25 between 25 between 26 meals the diets were assessed on the basis of qualitative meal classification method of bieliiska and kulesza . 0 ###LEFT-WALL### 2 diets 0 ###LEFT-WALL### 4 assessed 0 ###LEFT-WALL### 17 . 1 the 2 diets 2 diets 3 were 3 were 4 assessed 4 assessed 5 on 5 on 7 basis 6 the 7 basis 7 basis 8 of 8 of 12 method 9 qualitative 10 meal 10 meal 12 method 11 classification 12 method 12 method 13 of 13 of 15 and 14 bieliiska 15 and 15 and 16 kulesza results : individuals living in nursing homes consumed meals more often than living at homes , while ad did not have any impact on it . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 3 individuals 2 : 8 consumed 3 individuals 4 living 3 individuals 8 consumed 4 living 5 in 5 in 7 homes 6 nursing 7 homes 8 consumed 9 meals 9 meals 13 living 10 more 11 often 11 often 13 living 12 than 13 living 13 living 14 at 13 living 17 while 14 at 15 homes 16 , 17 while 17 while 18 ad 17 while 21 have 17 while 26 . 18 ad 19 did 19 did 20 not 19 did 21 have 21 have 23 impact 21 have 24 on 22 any 23 impact 24 on 25 it individuals consuming fruits and vegetables not often enough were in all the groups , however , in case of individuals living at homes it was serious [problem] . 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 6 not 1 individuals 2 consuming 1 individuals 4 and 2 consuming 3 fruits 4 and 5 vegetables 6 not 7 often 6 not 8 enough 6 not 9 were 8 enough 9 were 9 were 10 in 9 were 15 however 9 were 18 case 10 in 11 all 11 all 12 the 11 all 13 groups 12 the 13 groups 14 , 15 however 15 however 16 , 16 , 18 case 17 in 18 case 18 case 24 it 18 case 25 was 18 case 28 . 19 of 20 individuals 19 of 24 it 20 individuals 21 living 21 living 22 at 22 at 23 homes 24 it 25 was 25 was 26 serious consuming animal products to almost all main meals was observed in case of many individuals in all analyzed groups . 0 ###LEFT-WALL### 1 consuming 0 ###LEFT-WALL### 10 observed 0 ###LEFT-WALL### 20 . 1 consuming 3 products 1 consuming 4 to 1 consuming 9 was 2 animal 3 products 4 to 8 meals 5 almost 6 all 6 all 8 meals 7 main 8 meals 9 was 10 observed 10 observed 13 of 10 observed 16 in 11 in 12 case 12 case 13 of 13 of 15 individuals 14 many 15 individuals 16 in 19 groups 17 all 19 groups 18 analyzed 19 groups composition of majority of main meals and small amount of lunches and afternoon snacks was rational . 0 ###LEFT-WALL### 1 composition 0 ###LEFT-WALL### 15 was 0 ###LEFT-WALL### 17 . 1 composition 2 of 1 composition 15 was 2 of 7 and 3 majority 4 of 3 majority 7 and 4 of 6 meals 5 main 6 meals 7 and 9 amount 7 and 10 of 8 small 9 amount 10 of 12 and 11 lunches 12 and 12 and 14 snacks 13 afternoon 14 snacks 15 was 16 rational conclusions : improperly balanced diet following observed not only in a group of ad individuals but also of ones without dementia ( both living at homes and in nursing homes ) [,] may result in dietary deficiencies . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 8 not 0 ###LEFT-WALL### 38 . 1 conclusions 2 : 2 : 7 observed 3 improperly 4 balanced 4 balanced 6 following 5 diet 6 following 6 following 7 observed 8 not 9 only 8 not 15 individuals 8 not 34 result 10 in 14 ad 10 in 15 individuals 11 a 12 group 12 group 13 of 12 group 14 ad 13 of 14 ad 15 individuals 16 but 15 individuals 18 of 15 individuals 20 without 15 individuals 33 may 16 but 17 also 18 of 19 ones 20 without 21 dementia 21 dementia 24 living 22 ( 24 living 23 both 24 living 24 living 27 and 24 living 31 ) 25 at 26 homes 25 at 27 and 27 and 28 in 28 in 29 nursing 29 nursing 30 homes 33 may 34 result 34 result 35 in 35 in 37 deficiencies 36 dietary 37 deficiencies [none] background : limited evidence exists on the utilization of surveillance colonoscopy in colorectal cancer ( crc ) screening programs . 0 ###LEFT-WALL### 2 background 0 ###LEFT-WALL### 3 : 0 ###LEFT-WALL### 21 . 3 : 5 evidence 3 : 6 exists 4 limited 5 evidence 5 evidence 6 exists 6 exists 7 on 7 on 9 utilization 8 the 9 utilization 9 utilization 10 of 10 of 11 surveillance 11 surveillance 12 colonoscopy 11 surveillance 19 screening 12 colonoscopy 13 in 13 in 15 cancer 14 colorectal 15 cancer 15 cancer 17 crc 16 ( 17 crc 17 crc 18 ) 19 screening 20 programs we assessed adherence [to] physician recommendations for surveillance in opportunistic crc screening in germany . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 assessed 0 ###LEFT-WALL### 15 . 1 we 2 assessed 2 assessed 6 recommendations 2 assessed 9 in 3 adherence 6 recommendations 5 physician 6 recommendations 6 recommendations 7 for 7 for 8 surveillance 9 in 11 crc 10 opportunistic 11 crc 11 crc 12 screening 12 screening 13 in 12 screening 14 germany methods : [a] follow - up study of screening colonoscopy participants in 2007 - 2009 in saarland , germany , was conducted using health insurance claims data . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 4 follow 0 ###LEFT-WALL### 5 - 1 methods 2 : 2 : 4 follow 5 - 7 study 5 - 22 conducted 5 - 28 . 6 up 7 study 7 study 8 of 7 study 22 conducted 8 of 9 screening 9 screening 11 participants 10 colonoscopy 11 participants 11 participants 12 in 11 participants 17 saarland 11 participants 21 was 12 in 16 in 13 2007 14 - 14 - 15 2009 14 - 16 in 17 saarland 19 germany 17 saarland 21 was 18 , 19 germany 19 germany 20 , 22 conducted 23 using 22 conducted 27 data 23 using 26 claims 24 health 26 claims 25 insurance 26 claims utilization of additional colonoscopies through to 2011 was ascertained . 0 ###LEFT-WALL### 1 utilization 0 ###LEFT-WALL### 9 ascertained 0 ###LEFT-WALL### 10 . 1 utilization 2 of 1 utilization 8 was 2 of 4 colonoscopies 3 additional 4 colonoscopies 4 colonoscopies 5 through 5 through 6 to 6 to 7 2011 8 was 9 ascertained adherence to surveillance intervals of 3 , 6 , 12 and 36 months , defined as having had colonoscopy at 2.5 to 4 , 5 to 8 , 10.5 to 16 and 33 to 48 months , respectively [(] i.e [.] , tolerating a delay of 33 % of each interval ) was assessed . 0 ###LEFT-WALL### 1 adherence 0 ###LEFT-WALL### 18 had 0 ###LEFT-WALL### 32 and 0 ###LEFT-WALL### 55 . 1 adherence 2 to 1 adherence 18 had 2 to 4 intervals 3 surveillance 4 intervals 4 intervals 5 of 4 intervals 15 defined 4 intervals 16 as 5 of 6 3 6 3 8 6 6 3 13 months 7 , 8 6 8 6 9 , 9 , 13 months 10 12 11 and 11 and 12 36 11 and 13 months 13 months 14 , 16 as 17 having 18 had 19 colonoscopy 18 had 22 to 18 had 30 to 19 colonoscopy 20 at 20 at 21 2.5 22 to 23 4 23 4 26 to 24 , 26 to 25 5 26 to 26 to 27 8 26 to 28 , 29 10.5 30 to 30 to 31 16 32 and 33 33 32 and 54 assessed 33 33 34 to 33 33 43 tolerating 33 33 53 was 34 to 36 months 35 48 36 months 36 months 40 i.e 37 , 40 i.e 38 respectively 40 i.e 40 i.e 42 , 42 , 43 tolerating 43 tolerating 45 delay 43 tolerating 52 ) 44 a 45 delay 45 delay 46 of 45 delay 49 of 46 of 48 % 47 33 48 % 49 of 51 interval 50 each 51 interval 53 was 54 assessed potential predictors [of] [non] - adherence [were] investigated using logistic regression analysis . 0 ###LEFT-WALL### 2 predictors 0 ###LEFT-WALL### 5 - 0 ###LEFT-WALL### 13 . 1 potential 2 predictors 5 - 12 analysis 6 adherence 8 investigated 8 investigated 12 analysis 9 using 12 analysis 10 logistic 11 regression 11 regression 12 analysis results : a total of 20,058 screening colonoscopy participants were included in the study . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 15 . 2 : 4 total 3 a 4 total 4 total 5 of 5 of 6 20,058 6 20,058 7 screening 6 20,058 11 included 7 screening 8 colonoscopy 8 colonoscopy 9 participants 8 colonoscopy 10 were 9 participants 10 were 11 included 12 in 12 in 14 study 13 the 14 study of those with recommended surveillance intervals of 3 , 6 , 12 and 36 months , 46.5 % ( 95 % - confidence [interval] [ ci ] : 37.3 - 55.7 % ) , 38.5 % ( 95 % - ci : 29.6 - 47.3 % ) , 25.4 % ( 95 % - ci : 21.2 - 29.6 % ) and 28.0 % ( 95 % - ci : 25.5 - 30.5 % ) , respectively , had a subsequent colonoscopy within the specified margins . 0 ###LEFT-WALL### 23 confidence 0 ###LEFT-WALL### 28 : 0 ###LEFT-WALL### 40 - 0 ###LEFT-WALL### 87 . 1 of 2 those 1 of 23 confidence 2 those 3 with 3 with 6 intervals 4 recommended 5 surveillance 5 surveillance 6 intervals 6 intervals 7 of 6 intervals 15 months 7 of 8 3 8 3 10 6 9 , 10 6 10 6 11 , 11 , 15 months 12 12 13 and 13 and 14 36 13 and 15 months 15 months 18 % 15 months 22 - 16 , 18 % 17 46.5 18 % 18 % 21 % 18 % 22 - 19 ( 21 % 20 95 21 % 21 % 22 - 23 confidence 26 ci 23 confidence 28 : 25 [ 26 ci 26 ci 27 ] 28 : 29 37.3 29 37.3 32 % 29 37.3 36 % 30 - 32 % 31 55.7 32 % 32 % 33 ) 34 , 36 % 35 38.5 36 % 36 % 39 % 36 % 40 - 37 ( 39 % 38 95 39 % 39 % 40 - 40 - 41 ci 40 - 42 : 40 - 56 : 40 - 62 and 41 ci 42 : 42 : 43 29.6 43 29.6 46 % 43 29.6 50 % 44 - 46 % 45 47.3 46 % 46 % 47 ) 48 , 50 % 49 25.4 50 % 50 % 53 % 50 % 55 ci 50 % 56 : 51 ( 53 % 52 95 53 % 53 % 54 - 54 - 55 ci 55 ci 56 : 56 : 57 21.2 57 21.2 60 % 58 - 60 % 59 29.6 60 % 60 % 61 ) 62 and 64 % 62 and 79 had 63 28.0 64 % 64 % 67 % 64 % 79 had 65 ( 67 % 66 95 67 % 67 % 74 % 67 % 76 , 68 - 74 % 69 ci 70 : 70 : 72 - 71 25.5 72 - 72 - 73 30.5 73 30.5 74 % 74 % 75 ) 76 , 77 respectively 77 respectively 78 , 77 respectively 79 had 79 had 82 colonoscopy 79 had 83 within 80 a 81 subsequent 80 a 82 colonoscopy 81 subsequent 82 colonoscopy 83 within 86 margins 84 the 86 margins 85 specified 86 margins old age , longer recommended surveillance interval , not having had polypectomy at screening and negative colonoscopy were statistically significant predictors [of] [non] - adherence . 0 ###LEFT-WALL### 2 age 0 ###LEFT-WALL### 3 , 1 old 2 age 3 , 7 interval 3 , 8 , 4 longer 6 surveillance 5 recommended 6 surveillance 6 surveillance 7 interval 8 , 17 colonoscopy 8 , 18 were 8 , 24 - 9 not 10 having 9 not 17 colonoscopy 10 having 11 had 11 had 12 polypectomy 11 had 13 at 13 at 15 and 14 screening 15 and 15 and 16 negative 17 colonoscopy 18 were 18 were 19 statistically 18 were 21 predictors 20 significant 21 predictors 24 - 25 adherence 24 - 26 . conclusion : this study suggests frequent [non] - adherence [to] physician recommendations for surveillance colonoscopy in community practice . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 4 study 2 : 5 suggests 2 : 19 . 3 this 4 study 4 study 5 suggests 5 suggests 12 recommendations 5 suggests 15 colonoscopy 6 frequent 8 - 6 frequent 9 adherence 9 adherence 12 recommendations 11 physician 12 recommendations 12 recommendations 13 for 12 recommendations 15 colonoscopy 13 for 14 surveillance 15 colonoscopy 16 in 16 in 18 practice 17 community 18 practice increased efforts to improve [adherence] , including introduction of more elements of an organized screening program , seem necessary to assure a high - quality crc screening process . 0 ###LEFT-WALL### 2 efforts 0 ###LEFT-WALL### 18 seem 0 ###LEFT-WALL### 29 . 1 increased 2 efforts 2 efforts 3 to 2 efforts 4 improve 2 efforts 18 seem 3 to 4 improve 4 improve 7 including 6 , 7 including 7 including 8 introduction 7 including 17 , 8 introduction 9 of 8 introduction 12 of 9 of 11 elements 10 more 11 elements 12 of 16 program 13 an 14 organized 13 an 16 program 14 organized 16 program 15 screening 16 program 18 seem 19 necessary 19 necessary 20 to 19 necessary 27 screening 20 to 21 assure 21 assure 26 crc 22 a 23 high 22 a 26 crc 23 high 24 - 23 high 26 crc 25 quality 26 crc 26 crc 27 screening 27 screening 28 process alzheimer 's disease ( ad ) is associated with abnormal functioning of the default mode network ( dmn ) . 0 ###LEFT-WALL### 3 disease 0 ###LEFT-WALL### 8 associated 0 ###LEFT-WALL### 20 . 1 alzheimer 2 's 2 's 3 disease 3 disease 5 ad 3 disease 7 is 4 ( 5 ad 5 ad 6 ) 7 is 8 associated 8 associated 9 with 9 with 11 functioning 10 abnormal 11 functioning 11 functioning 12 of 12 of 16 network 13 the 16 network 14 default 16 network 15 mode 16 network 16 network 18 dmn 17 ( 18 dmn 18 dmn 19 ) functional connectivity ( fc ) changes to the dmn have been found in patients with amnestic mild cognitive impairment ( amci ) , [which] is the prodromal stage of ad . 0 ###LEFT-WALL### 1 functional 0 ###LEFT-WALL### 23 , 0 ###LEFT-WALL### 31 . 1 functional 2 connectivity 1 functional 6 changes 1 functional 23 , 2 connectivity 4 fc 2 connectivity 6 changes 3 ( 4 fc 4 fc 5 ) 6 changes 7 to 7 to 9 dmn 8 the 9 dmn 10 have 11 been 10 have 23 , 11 been 12 found 12 found 13 in 13 in 14 patients 14 patients 15 with 15 with 19 impairment 16 amnestic 19 impairment 17 mild 19 impairment 18 cognitive 19 impairment 19 impairment 21 amci 20 ( 21 amci 21 amci 22 ) 23 , 25 is 25 is 28 stage 26 the 28 stage 27 prodromal 28 stage 28 stage 29 of 29 of 30 ad however , whether or not amci also alters the effective connectivity ( ec ) [of] the dmn remains unknown . 0 ###LEFT-WALL### 17 dmn 0 ###LEFT-WALL### 18 remains 0 ###LEFT-WALL### 20 . 1 however 2 , 1 however 17 dmn 2 , 5 not 3 whether 4 or 4 or 5 not 5 not 6 amci 5 not 8 alters 5 not 14 ) 5 not 17 dmn 6 amci 8 alters 7 also 8 alters 8 alters 11 connectivity 9 the 11 connectivity 10 effective 11 connectivity 11 connectivity 13 ec 12 ( 13 ec 13 ec 14 ) 16 the 17 dmn 17 dmn 18 remains 18 remains 19 unknown bn analysis demonstrated heterogeneous regional convergence degree [across] dmn regions , which were organized into two closely interacting subsystems . 0 ###LEFT-WALL### 10 regions 0 ###LEFT-WALL### 11 , 0 ###LEFT-WALL### 20 . 1 bn 2 analysis 2 analysis 10 regions 3 demonstrated 6 convergence 4 heterogeneous 6 convergence 5 regional 6 convergence 6 convergence 7 degree 7 degree 10 regions 9 dmn 10 regions 11 , 12 which 11 , 14 organized 12 which 13 were 13 were 14 organized 14 organized 15 into 15 into 19 subsystems 16 two 19 subsystems 17 closely 18 interacting 18 interacting 19 subsystems compared to controls , the amci group showed altered directed connectivity weights between dmn regions in the fronto - parietal , temporo - frontal , and temporo - parietal pathways . 0 ###LEFT-WALL### 7 group 0 ###LEFT-WALL### 8 showed 0 ###LEFT-WALL### 31 . 1 compared 2 to 1 compared 4 , 1 compared 7 group 2 to 3 controls 5 the 7 group 6 amci 7 group 7 group 8 showed 8 showed 12 weights 8 showed 13 between 8 showed 15 regions 8 showed 16 in 9 altered 12 weights 10 directed 11 connectivity 11 connectivity 12 weights 13 between 14 dmn 16 in 30 pathways 17 the 30 pathways 18 fronto 22 temporo 18 fronto 30 pathways 19 - 22 temporo 20 parietal 21 , 20 parietal 22 temporo 22 temporo 26 and 22 temporo 28 - 23 - 26 and 24 frontal 26 and 25 , 26 and 26 and 27 temporo 26 and 28 - 29 parietal 30 pathways the amci group also exhibited altered regional convergence [degree] in the right inferior parietal lobule . 0 ###LEFT-WALL### 3 group 0 ###LEFT-WALL### 6 altered 0 ###LEFT-WALL### 16 . 1 the 3 group 2 amci 3 group 3 group 5 exhibited 3 group 6 altered 4 also 5 exhibited 6 altered 8 convergence 6 altered 10 in 7 regional 8 convergence 10 in 15 lobule 11 the 15 lobule 12 right 15 lobule 13 inferior 15 lobule 14 parietal 15 lobule moreover , we found ec changes in dmn regions in amci were correlated with regional fc levels , and the connectivity metrics were associated with patients ' cognitive performance . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 found 0 ###LEFT-WALL### 19 and 0 ###LEFT-WALL### 30 . 1 moreover 2 , 1 moreover 3 we 3 we 4 found 4 found 6 changes 4 found 13 correlated 5 ec 6 changes 6 changes 7 in 6 changes 9 regions 6 changes 12 were 6 changes 13 correlated 7 in 8 dmn 9 regions 10 in 9 regions 12 were 10 in 11 amci 13 correlated 14 with 14 with 17 levels 15 regional 17 levels 16 fc 17 levels 18 , 19 and 19 and 22 metrics 19 and 24 associated 20 the 22 metrics 21 connectivity 22 metrics 22 metrics 23 were 23 were 24 associated 24 associated 25 with 25 with 29 performance 26 patients 27 ' 27 ' 29 performance 28 cognitive 29 performance this study provides novel sights into our understanding of the functional architecture of the dmn and adds to a growing body of work demonstrating the importance of the dmn as a mechanism of amci . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 16 and 0 ###LEFT-WALL### 35 . 1 this 2 study 2 study 16 and 3 provides 5 sights 3 provides 6 into 3 provides 16 and 4 novel 5 sights 6 into 8 understanding 7 our 8 understanding 8 understanding 9 of 8 understanding 13 of 9 of 12 architecture 10 the 12 architecture 11 functional 12 architecture 13 of 15 dmn 14 the 15 dmn 16 and 17 adds 16 and 18 to 16 and 30 as 18 to 21 body 19 a 21 body 20 growing 21 body 21 body 22 of 21 body 27 of 22 of 23 work 23 work 24 demonstrating 24 demonstrating 26 importance 25 the 26 importance 27 of 29 dmn 28 the 29 dmn 30 as 32 mechanism 31 a 32 mechanism 32 mechanism 33 of 33 of 34 amci long interspersed element - 1 ( line - 1 , l1 ) is an active retrotransposon that mobilizes using a ribonucleoprotein particle ( rnp ) intermediate composed of the full - length bicistronic l1 mrna and the two proteins ( orf1p and orf2p ) encoded by that mrna . 0 ###LEFT-WALL### 3 element 0 ###LEFT-WALL### 13 is 1 long 2 interspersed 2 interspersed 3 element 3 element 5 1 3 element 11 l1 3 element 13 is 4 - 5 1 5 1 7 line 5 1 10 , 6 ( 7 line 7 line 9 1 7 line 10 , 8 - 9 1 9 1 10 , 10 , 11 l1 11 l1 12 ) 13 is 16 retrotransposon 14 an 16 retrotransposon 15 active 16 retrotransposon 16 retrotransposon 17 that 16 retrotransposon 18 mobilizes 17 that 18 mobilizes 18 mobilizes 19 using 18 mobilizes 36 and 19 using 22 particle 20 a 22 particle 21 ribonucleoprotein 22 particle 22 particle 24 rnp 23 ( 24 rnp 24 rnp 25 ) 26 intermediate 27 composed 26 intermediate 28 of 26 intermediate 36 and 28 of 35 mrna 29 the 35 mrna 30 full 31 - 30 full 32 length 32 length 35 mrna 33 bicistronic 35 mrna 34 l1 35 mrna 36 and 39 proteins 36 and 42 and 37 the 39 proteins 38 two 39 proteins 40 ( 42 and 41 orf1p 42 and 42 and 43 orf2p 42 and 44 ) 42 and 45 encoded 42 and 46 by 42 and 49 . 46 by 48 mrna 47 that 48 mrna orf1p and orf2p demonstrate cis - preference for their encoding mrna . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 4 demonstrate 0 ###LEFT-WALL### 12 . 1 orf1p 2 and 2 and 3 orf2p 2 and 4 demonstrate 4 demonstrate 7 preference 5 cis 6 - 5 cis 7 preference 7 preference 8 for 8 for 11 mrna 9 their 11 mrna 10 encoding 11 mrna previous studies of orf1p [,] purified from bacterial and insect cells demonstrated that this protein forms trimers in vitro . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 12 demonstrated 0 ###LEFT-WALL### 20 . 1 previous 2 studies 2 studies 3 of 2 studies 12 demonstrated 3 of 4 orf1p 4 orf1p 6 purified 6 purified 7 from 7 from 9 and 8 bacterial 9 and 9 and 11 cells 10 insect 11 cells 12 demonstrated 13 that 13 that 15 protein 13 that 16 forms 14 this 15 protein 15 protein 16 forms 16 forms 17 trimers 16 forms 19 vitro 18 in 19 vitro while valuable for understanding orf1p function , [these] in vitro approaches do not provide any information on orf1p self [-] interaction in the context of mammalian cells . 0 ###LEFT-WALL### 6 function 0 ###LEFT-WALL### 7 , 0 ###LEFT-WALL### 28 . 1 while 2 valuable 1 while 6 function 2 valuable 3 for 3 for 4 understanding 4 understanding 5 orf1p 7 , 11 approaches 7 , 14 provide 9 in 10 vitro 10 vitro 11 approaches 11 approaches 12 do 12 do 13 not 12 do 14 provide 14 provide 16 information 14 provide 17 on 14 provide 22 in 15 any 16 information 17 on 21 interaction 18 orf1p 21 interaction 19 self 21 interaction 22 in 24 context 23 the 24 context 24 context 25 of 25 of 27 cells 26 mammalian 27 cells we used a mammalian [two] - hybrid ( m2h ) system in order to study l1 orf1p self [-] interaction in human and mouse cells . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 used 0 ###LEFT-WALL### 26 . 1 we 2 used 2 used 11 system 2 used 12 in 2 used 14 to 2 used 15 study 3 a 4 mammalian 3 a 11 system 4 mammalian 6 - 4 mammalian 11 system 7 hybrid 9 m2h 7 hybrid 10 ) 7 hybrid 11 system 8 ( 9 m2h 9 m2h 10 ) 12 in 13 order 14 to 15 study 15 study 20 interaction 15 study 21 in 16 l1 17 orf1p 17 orf1p 18 self 18 self 20 interaction 21 in 23 and 22 human 23 and 23 and 25 cells 24 mouse 25 cells we demonstrate that the m2h system successfully detects human and mouse orf1p self - interactions in transiently transfected mammalian cells . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 demonstrate 0 ###LEFT-WALL### 14 - 0 ###LEFT-WALL### 21 . 1 we 2 demonstrate 2 demonstrate 3 that 3 that 6 system 3 that 8 detects 4 the 6 system 5 m2h 6 system 6 system 8 detects 7 successfully 8 detects 8 detects 10 and 9 human 10 and 10 and 13 self 11 mouse 13 self 12 orf1p 13 self 14 - 15 interactions 15 interactions 16 in 16 in 20 cells 17 transiently 18 transfected 18 transfected 20 cells 19 mammalian 20 cells we also generated mouse [and] human [orf1p] - specific antibodies to characterize the expression of orf1p fusion proteins used in the m2h system . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 generated 0 ###LEFT-WALL### 24 . 1 we 3 generated 2 also 3 generated 3 generated 10 antibodies 3 generated 11 to 4 mouse 10 antibodies 6 human 8 - 6 human 10 antibodies 9 specific 10 antibodies 11 to 12 characterize 12 characterize 14 expression 12 characterize 20 in 13 the 14 expression 14 expression 15 of 15 of 16 orf1p 16 orf1p 18 proteins 16 orf1p 19 used 17 fusion 18 proteins 18 proteins 19 used 20 in 23 system 21 the 23 system 22 m2h 23 system using these antibodies , we demonstrate that orf1p interaction in trans leads to the formation of heterodimers that are expected to produce a positive signal in the m2h system . 0 ###LEFT-WALL### 5 we 0 ###LEFT-WALL### 6 demonstrate 0 ###LEFT-WALL### 30 . 1 using 3 antibodies 1 using 4 , 1 using 5 we 2 these 3 antibodies 5 we 6 demonstrate 6 demonstrate 9 interaction 6 demonstrate 12 leads 7 that 9 interaction 8 orf1p 9 interaction 9 interaction 10 in 9 interaction 12 leads 10 in 11 trans 12 leads 13 to 13 to 15 formation 14 the 15 formation 15 formation 16 of 16 of 17 heterodimers 17 heterodimers 18 that 17 heterodimers 19 are 18 that 19 are 19 are 20 expected 20 expected 21 to 20 expected 22 produce 21 to 22 produce 22 produce 25 signal 22 produce 26 in 23 a 24 positive 23 a 25 signal 24 positive 25 signal 26 in 29 system 27 the 29 system 28 m2h 29 system although the role for l1 orf1p cis - preference in l1 mobilization is established , the impact of ability of orf1pto [interact] in trans on the l1 replication cycle is not known . 0 ###LEFT-WALL### 9 preference 0 ###LEFT-WALL### 14 established 0 ###LEFT-WALL### 15 , 0 ###LEFT-WALL### 33 . 1 although 3 role 1 although 9 preference 2 the 3 role 3 role 4 for 4 for 6 orf1p 5 l1 6 orf1p 7 cis 8 - 7 cis 9 preference 9 preference 10 in 9 preference 13 is 10 in 12 mobilization 11 l1 12 mobilization 13 is 14 established 15 , 17 impact 15 , 32 known 16 the 17 impact 17 impact 18 of 17 impact 23 in 17 impact 30 is 18 of 19 ability 19 ability 20 of 20 of 21 orf1pto 23 in 24 trans 24 trans 25 on 25 on 29 cycle 26 the 29 cycle 27 l1 29 cycle 28 replication 29 cycle 30 is 31 not 30 is 32 known furthermore , western blot analysis of orf1p generated by a full - length l1 , wild type orf1 , or a codon - optimized orf1 expression [vector] is detected in the nucleus . 0 ###LEFT-WALL### 5 analysis 0 ###LEFT-WALL### 29 detected 0 ###LEFT-WALL### 33 . 1 furthermore 2 , 1 furthermore 5 analysis 3 western 5 analysis 4 blot 5 analysis 5 analysis 6 of 5 analysis 8 generated 5 analysis 28 is 6 of 7 orf1p 8 generated 9 by 9 by 13 length 10 a 11 full 10 a 13 length 11 full 12 - 11 full 13 length 13 length 14 l1 13 length 24 optimized 14 l1 20 or 14 l1 24 optimized 15 , 20 or 16 wild 17 type 17 type 18 orf1 18 orf1 20 or 19 , 20 or 20 or 22 codon 20 or 23 - 21 a 22 codon 24 optimized 26 expression 25 orf1 26 expression 28 is 29 detected 29 detected 30 in 30 in 32 nucleus 31 the 32 nucleus in contrast , the addition of a tag to the [n] [-] terminus of the mouse and human orf1 proteins can significantly alter the subcellular localization in a tag - specific manner . 0 ###LEFT-WALL### 5 addition 0 ###LEFT-WALL### 23 alter 0 ###LEFT-WALL### 30 - 0 ###LEFT-WALL### 33 . 1 in 2 contrast 1 in 3 , 1 in 5 addition 4 the 5 addition 5 addition 6 of 5 addition 21 can 6 of 8 tag 7 a 8 tag 8 tag 9 to 8 tag 14 of 9 to 13 terminus 10 the 13 terminus 14 of 17 and 15 the 16 mouse 16 mouse 17 and 17 and 20 proteins 18 human 20 proteins 19 orf1 20 proteins 21 can 23 alter 22 significantly 23 alter 23 alter 26 localization 23 alter 27 in 24 the 26 localization 25 subcellular 26 localization 27 in 29 tag 28 a 29 tag 30 - 32 manner 31 specific 32 manner these data support that nuclear localization [of] orf1p may contribute to l1 ( and [potentially] the sine alu ) rnp nuclear access in the host cell . 0 ###LEFT-WALL### 2 data 0 ###LEFT-WALL### 3 support 0 ###LEFT-WALL### 27 . 1 these 2 data 2 data 3 support 3 support 6 localization 3 support 11 to 3 support 23 in 4 that 5 nuclear 5 nuclear 6 localization 6 localization 8 orf1p 6 localization 10 contribute 8 orf1p 9 may 9 may 10 contribute 11 to 22 access 12 l1 14 and 13 ( 14 and 14 and 18 alu 14 and 19 ) 14 and 22 access 16 the 18 alu 17 sine 18 alu 20 rnp 22 access 21 nuclear 22 access 23 in 26 cell 24 the 26 cell 25 host 26 cell background : in the elderly , the ankle - brachial index ( abi ) [has] greater than 90 % sensitivity and specificity for peripheral artery disease identification . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 28 . 1 background 2 : 2 : 3 in 2 : 16 greater 3 in 11 index 4 the 11 index 5 elderly 8 ankle 5 elderly 11 index 6 , 8 ankle 7 the 8 ankle 8 ankle 9 - 10 brachial 11 index 11 index 13 abi 12 ( 13 abi 13 abi 14 ) 16 greater 17 than 16 greater 23 for 17 than 21 and 18 90 19 % 19 % 20 sensitivity 20 sensitivity 21 and 21 and 22 specificity 23 for 27 identification 24 peripheral 25 artery 25 artery 27 identification 26 disease 27 identification a well - known relation exists between peripheral artery disease and the number of diseased coronary vessels . 0 ###LEFT-WALL### 2 well 0 ###LEFT-WALL### 3 - 1 a 2 well 3 - 5 relation 3 - 6 exists 3 - 18 . 4 known 5 relation 5 relation 6 exists 6 exists 7 between 7 between 11 and 8 peripheral 9 artery 9 artery 10 disease 10 disease 11 and 11 and 13 number 11 and 14 of 12 the 13 number 14 of 17 vessels 15 diseased 17 vessels 16 coronary 17 vessels yet , other anatomical characteristics have important impacts on the type of treatment and prognosis . 0 ###LEFT-WALL### 5 characteristics 0 ###LEFT-WALL### 6 have 0 ###LEFT-WALL### 16 . 1 yet 2 , 1 yet 5 characteristics 3 other 5 characteristics 4 anatomical 5 characteristics 5 characteristics 6 have 6 have 8 impacts 6 have 9 on 7 important 8 impacts 9 on 14 and 10 the 11 type 11 type 12 of 11 type 13 treatment 12 of 13 treatment 13 treatment 14 and 14 and 15 prognosis purpose : to determine the relation between abi and the complexity of coronary artery disease , by different anatomical classifications . 0 ###LEFT-WALL### 1 purpose 0 ###LEFT-WALL### 2 : 2 : 3 to 2 : 4 determine 3 to 4 determine 4 determine 6 relation 4 determine 7 between 4 determine 17 by 5 the 6 relation 7 between 9 and 8 abi 9 and 9 and 11 complexity 10 the 11 complexity 11 complexity 12 of 12 of 15 disease 13 coronary 15 disease 14 artery 15 disease 16 , 17 by 17 by 20 classifications 17 by 21 . 18 different 20 classifications 19 anatomical 20 classifications methods : this study was a prospective analysis of patients ≥65 years old [who] were undergoing elective coronary angiography for ischemic coronary disease . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 4 study 2 : 16 undergoing 2 : 24 . 3 this 4 study 4 study 5 was 5 was 8 analysis 6 a 7 prospective 6 a 8 analysis 7 prospective 8 analysis 8 analysis 9 of 8 analysis 11 ≥65 8 analysis 16 undergoing 9 of 10 patients 11 ≥65 13 old 11 ≥65 15 were 12 years 13 old 15 were 16 undergoing 16 undergoing 19 angiography 17 elective 18 coronary 18 coronary 19 angiography 19 angiography 20 for 20 for 23 disease 21 ischemic 23 disease 22 coronary 23 disease the abi was calculated for each leg , as the ratio between the lowest ankle pressure and the highest brachial pressure . 0 ###LEFT-WALL### 2 abi 0 ###LEFT-WALL### 4 calculated 1 the 2 abi 2 abi 3 was 3 was 4 calculated 4 calculated 5 for 5 for 7 leg 6 each 7 leg 7 leg 9 as 8 , 9 as 9 as 11 ratio 9 as 22 . 10 the 11 ratio 11 ratio 12 between 12 between 17 and 13 the 14 lowest 13 the 16 pressure 15 ankle 16 pressure 16 pressure 17 and 17 and 21 pressure 18 the 19 highest 18 the 21 pressure 20 brachial 21 pressure the analysis of coronary anatomy was performed by three interventional cardiologists ; it included classification of each lesion with >50 % diameter stenosis , according to the american heart association criteria , and calculation of the syntax score . 0 ###LEFT-WALL### 2 analysis 0 ###LEFT-WALL### 7 performed 0 ###LEFT-WALL### 12 ; 0 ###LEFT-WALL### 39 . 1 the 2 analysis 2 analysis 3 of 2 analysis 6 was 3 of 5 anatomy 4 coronary 5 anatomy 6 was 7 performed 7 performed 8 by 8 by 11 cardiologists 9 three 11 cardiologists 10 interventional 11 cardiologists 12 ; 13 it 12 ; 14 included 12 ; 24 , 13 it 14 included 14 included 15 classification 14 included 19 with 15 classification 16 of 16 of 18 lesion 17 each 18 lesion 19 with 23 stenosis 20 >50 23 stenosis 21 % 23 stenosis 22 diameter 23 stenosis 24 , 38 score 25 according 26 to 26 to 33 and 26 to 38 score 27 the 31 criteria 28 american 31 criteria 29 heart 30 association 30 association 31 criteria 31 criteria 33 and 32 , 33 and 33 and 34 calculation 34 calculation 35 of 35 of 37 syntax 36 the 37 syntax results : the study recruited 204 consecutive patients ( median age : 72.5 years [ )( 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 4 study 2 : 5 recruited 2 : 12 : 2 : 16 )( 3 the 4 study 4 study 5 recruited 5 recruited 8 patients 6 204 8 patients 7 consecutive 8 patients 8 patients 11 age 9 ( 11 age 10 median 11 age 11 age 12 : 12 : 14 years 13 72.5 14 years stable angina was present in 51 % of patients . 0 ###LEFT-WALL### 2 angina 0 ###LEFT-WALL### 3 was 0 ###LEFT-WALL### 10 . 1 stable 2 angina 2 angina 3 was 3 was 4 present 4 present 5 in 5 in 7 % 6 51 7 % 7 % 8 of 8 of 9 patients although only 1 % of patients reported peripheral artery disease , 45 % exhibited an abnormal abi . 0 ###LEFT-WALL### 13 % 0 ###LEFT-WALL### 14 exhibited 0 ###LEFT-WALL### 18 . 1 although 4 % 1 although 7 reported 1 although 11 , 1 although 13 % 2 only 3 1 3 1 4 % 4 % 5 of 4 % 7 reported 5 of 6 patients 7 reported 10 disease 8 peripheral 9 artery 9 artery 10 disease 12 45 13 % 13 % 14 exhibited 14 exhibited 17 abi 15 an 16 abnormal 15 an 17 abi 16 abnormal 17 abi the number of lesions per patient , the number of patients with complex lesions , and the median syntax scores were greater in the group with abnormal abi . 0 ###LEFT-WALL### 16 and 0 ###LEFT-WALL### 21 were 0 ###LEFT-WALL### 29 . 1 the 2 number 2 number 3 of 2 number 16 and 3 of 4 lesions 4 lesions 5 per 4 lesions 11 patients 5 per 6 patient 7 , 11 patients 8 the 9 number 9 number 10 of 9 number 11 patients 10 of 11 patients 11 patients 12 with 11 patients 15 , 12 with 14 lesions 13 complex 14 lesions 15 , 16 and 16 and 18 median 16 and 19 syntax 16 and 20 scores 16 and 21 were 17 the 18 median 19 syntax 20 scores 21 were 22 greater 22 greater 23 in 22 greater 26 with 23 in 25 group 24 the 25 group 26 with 28 abi 27 abnormal 28 abi conclusion : in patients ≥65 years old the presence of peripheral artery disease could discriminate a group of patients with greater occurrence of b2 and [c] type lesions , but similar median syntax score . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 35 . 2 : 9 presence 2 : 25 and 2 : 30 but 3 in 5 ≥65 3 in 9 presence 4 patients 5 ≥65 5 ≥65 7 old 6 years 7 old 8 the 9 presence 9 presence 10 of 9 presence 14 could 10 of 13 disease 11 peripheral 12 artery 12 artery 13 disease 14 could 25 and 15 discriminate 19 patients 15 discriminate 25 and 16 a 17 group 17 group 18 of 17 group 19 patients 18 of 19 patients 19 patients 20 with 20 with 22 occurrence 21 greater 22 occurrence 22 occurrence 23 of 23 of 24 b2 25 and 27 type 27 type 28 lesions 29 , 30 but 30 but 33 syntax 30 but 34 score 31 similar 33 syntax 32 median 33 syntax 33 syntax 34 score background : restorative home care services are short - [term] and aimed at maximizing a person 's ability to live independently . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 22 . 2 : 6 services 2 : 11 and 3 restorative 4 home 4 home 6 services 5 care 6 services 6 services 7 are 7 are 11 and 8 short 11 and 9 - 11 and 11 and 12 aimed 11 and 21 independently 12 aimed 13 at 12 aimed 19 to 12 aimed 20 live 13 at 14 maximizing 14 maximizing 18 ability 15 a 16 person 16 person 17 's 17 's 18 ability 19 to 20 live they are multidimensional and often [include] an exercise program to improve strength , mobility , and balance . 0 ###LEFT-WALL### 1 they 0 ###LEFT-WALL### 2 are 0 ###LEFT-WALL### 18 . 1 they 2 are 2 are 4 and 2 are 10 to 3 multidimensional 4 and 4 and 5 often 4 and 9 program 7 an 8 exercise 7 an 9 program 8 exercise 9 program 10 to 16 and 11 improve 12 strength 11 improve 16 and 12 strength 14 mobility 13 , 14 mobility 14 mobility 15 , 16 and 17 balance the aim of this study was to determine whether a lifestyle exercise program would be undertaken more often and result in greater functional gains than the current structured exercise program delivered as part of a restorative home care service for older adults . 0 ###LEFT-WALL### 2 aim 0 ###LEFT-WALL### 25 than 0 ###LEFT-WALL### 43 . 1 the 2 aim 2 aim 3 of 2 aim 6 was 3 of 5 study 4 this 5 study 6 was 7 to 6 was 19 and 7 to 19 and 8 determine 9 whether 8 determine 18 often 8 determine 19 and 9 whether 13 program 9 whether 16 undertaken 10 a 11 lifestyle 10 a 13 program 11 lifestyle 13 program 12 exercise 13 program 13 program 14 would 14 would 15 be 15 be 16 undertaken 17 more 18 often 19 and 20 result 19 and 21 in 21 in 24 gains 22 greater 24 gains 23 functional 24 gains 25 than 30 program 25 than 31 delivered 26 the 30 program 27 current 29 exercise 28 structured 29 exercise 29 exercise 30 program 30 program 31 delivered 31 delivered 32 as 32 as 33 part 33 part 34 of 34 of 39 service 35 a 36 restorative 35 a 39 service 36 restorative 37 home 37 home 38 care 38 care 39 service 39 service 40 for 40 for 42 adults 41 older 42 adults methods : a pragmatic randomized controlled trial was conducted in an organization with an established restorative home care service . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 7 trial 2 : 9 conducted 2 : 20 . 3 a 4 pragmatic 3 a 7 trial 4 pragmatic 7 trial 5 randomized 7 trial 6 controlled 7 trial 7 trial 8 was 8 was 9 conducted 9 conducted 10 in 9 conducted 13 with 10 in 12 organization 11 an 12 organization 13 with 19 service 14 an 19 service 15 established 17 home 16 restorative 17 home 17 home 19 service 18 care 19 service exercise data collected by the individuals throughout and pre and post intervention testing was used to measure balance , strength , mobility , [falls] efficacy , vitality , function , and disability . 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 33 . 1 exercise 2 data 2 data 3 collected 2 data 8 and 3 collected 4 by 3 collected 7 throughout 4 by 6 individuals 5 the 6 individuals 8 and 9 pre 8 and 10 and 10 and 11 post 10 and 13 testing 10 and 17 measure 12 intervention 13 testing 13 testing 14 was 14 was 15 used 15 used 16 to 15 used 17 measure 16 to 17 measure 17 measure 31 and 18 balance 19 , 19 , 20 strength 19 , 21 , 21 , 22 mobility 21 , 23 , 23 , 25 efficacy 23 , 26 , 26 , 27 vitality 26 , 28 , 28 , 29 function 28 , 31 and 30 , 31 and 31 and 32 disability results : there was no difference between the groups in the amounts of exercise undertaken during the 8 - week intervention period . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 3 there 2 : 4 was 2 : 19 - 3 there 4 was 4 was 6 difference 5 no 6 difference 6 difference 7 between 6 difference 13 of 7 between 9 groups 8 the 9 groups 9 groups 10 in 10 in 12 amounts 11 the 12 amounts 13 of 14 exercise 14 exercise 15 undertaken 15 undertaken 16 during 16 during 18 8 17 the 18 8 19 - 22 period 19 - 23 . 20 week 21 intervention 21 intervention 22 period outcome measurement indicated that the life program was as effective , [and] on 40 % of the measures , more effective , than the structured exercise program . 0 ###LEFT-WALL### 2 measurement 0 ###LEFT-WALL### 3 indicated 1 outcome 2 measurement 2 measurement 3 indicated 3 indicated 4 that 4 that 7 program 4 that 8 was 5 the 7 program 6 life 7 program 7 program 8 was 8 was 10 effective 9 as 10 effective 10 effective 13 on 11 , 13 on 13 on 15 % 13 on 28 . 14 40 15 % 15 % 16 of 16 of 18 measures 17 the 18 measures 18 measures 21 effective 18 measures 27 program 19 , 21 effective 20 more 21 effective 21 effective 22 , 22 , 23 than 22 , 27 program 24 the 27 program 25 structured 26 exercise 26 exercise 27 program 27 program 28 . conclusion : organizations delivering restorative home care services that include an exercise component should consider [whether] life rather than the exercise program they are currently using could help their clients achieve better outcomes . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 6 home 2 : 28 help 2 : 34 . 3 organizations 6 home 4 delivering 6 home 5 restorative 6 home 6 home 7 care 6 home 8 services 6 home 27 could 7 care 8 services 8 services 10 include 8 services 19 than 9 that 10 include 10 include 13 component 10 include 15 consider 11 an 12 exercise 11 an 13 component 12 exercise 13 component 13 component 14 should 14 should 15 consider 15 consider 17 life 18 rather 19 than 19 than 22 program 20 the 22 program 21 exercise 22 program 22 program 23 they 22 program 26 using 23 they 24 are 24 are 26 using 25 currently 26 using 27 could 28 help 28 help 30 clients 28 help 31 achieve 29 their 30 clients 31 achieve 32 better 31 achieve 33 outcomes the protein mutated in huntington disease ( hd ) , mutant huntingtin ( mhtt ) , is expressed throughout the brain and body . 0 ###LEFT-WALL### 2 protein 0 ###LEFT-WALL### 18 expressed 0 ###LEFT-WALL### 24 . 1 the 2 protein 2 protein 3 mutated 2 protein 17 is 3 mutated 4 in 4 in 6 disease 5 huntington 6 disease 6 disease 8 hd 6 disease 12 huntingtin 7 ( 8 hd 8 hd 9 ) 10 , 12 huntingtin 11 mutant 12 huntingtin 12 huntingtin 14 mhtt 12 huntingtin 16 , 13 ( 14 mhtt 14 mhtt 15 ) 17 is 18 expressed 18 expressed 19 throughout 19 throughout 22 and 20 the 21 brain 21 brain 22 and 22 and 23 body however , the pathology of hd is characterized by early and dramatic destruction [selectively] of the striatum . 0 ###LEFT-WALL### 4 pathology 0 ###LEFT-WALL### 8 characterized 0 ###LEFT-WALL### 18 . 1 however 2 , 1 however 4 pathology 3 the 4 pathology 4 pathology 5 of 4 pathology 7 is 5 of 6 hd 7 is 8 characterized 8 characterized 9 by 9 by 13 destruction 10 early 11 and 11 and 12 dramatic 11 and 13 destruction 13 destruction 15 of 15 of 17 striatum 16 the 17 striatum we previously reported that the striatal - specific protein rhes binds mhtt and enhances its cytotoxicity . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 17 . 1 we 13 and 2 previously 3 reported 3 reported 4 that 3 reported 13 and 4 that 11 binds 4 that 12 mhtt 5 the 11 binds 6 striatal 7 - 6 striatal 9 protein 8 specific 9 protein 9 protein 11 binds 10 rhes 11 binds 11 binds 12 mhtt 13 and 14 enhances 14 enhances 16 cytotoxicity 15 its 16 cytotoxicity moreover , rhes - deleted mice are dramatically protected from neurodegeneration and motor dysfunction in mouse models of hd . 0 ###LEFT-WALL### 6 mice 0 ###LEFT-WALL### 9 protected 0 ###LEFT-WALL### 20 . 1 moreover 2 , 1 moreover 6 mice 2 , 3 rhes 3 rhes 4 - 3 rhes 6 mice 5 deleted 6 mice 6 mice 7 are 7 are 9 protected 8 dramatically 9 protected 9 protected 10 from 9 protected 15 in 10 from 12 and 11 neurodegeneration 12 and 12 and 14 dysfunction 13 motor 14 dysfunction 15 in 17 models 16 mouse 17 models 17 models 18 of 18 of 19 hd we now report a function of rhes in autophagy , a lysosomal degradation pathway implicated in aging and hd neurodegeneration . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 report 0 ###LEFT-WALL### 21 . 1 we 3 report 2 now 3 report 3 report 5 function 3 report 8 in 4 a 5 function 5 function 6 of 6 of 7 rhes 8 in 18 and 9 autophagy 10 , 10 , 14 pathway 10 , 18 and 11 a 12 lysosomal 11 a 14 pathway 12 lysosomal 13 degradation 13 degradation 14 pathway 14 pathway 15 implicated 15 implicated 16 in 16 in 17 aging 18 and 20 neurodegeneration 19 hd 20 neurodegeneration in pc12 cells , deletion of endogenous rhes decreases autophagy , whereas rhes overexpression activates autophagy . 0 ###LEFT-WALL### 5 deletion 0 ###LEFT-WALL### 15 activates 0 ###LEFT-WALL### 17 . 1 in 3 cells 1 in 4 , 1 in 5 deletion 2 pc12 3 cells 5 deletion 6 of 5 deletion 9 decreases 6 of 8 rhes 7 endogenous 8 rhes 9 decreases 10 autophagy 9 decreases 12 whereas 11 , 12 whereas 12 whereas 14 overexpression 13 rhes 14 overexpression 14 overexpression 15 activates 15 activates 16 autophagy these effects are independent of mtor and opposite in the direction predicted by the known activation of mtor by rhes . 0 ###LEFT-WALL### 2 effects 0 ###LEFT-WALL### 3 are 0 ###LEFT-WALL### 21 . 1 these 2 effects 2 effects 3 are 3 are 7 and 4 independent 5 of 4 independent 7 and 5 of 6 mtor 7 and 8 opposite 7 and 9 in 7 and 12 predicted 9 in 11 direction 10 the 11 direction 12 predicted 13 by 12 predicted 19 by 13 by 16 activation 14 the 16 activation 15 known 16 activation 16 activation 17 of 17 of 18 mtor 19 by 20 rhes rhes robustly binds the autophagy regulator beclin - 1 , decreasing its inhibitory interaction with bcl - 2 independent of jnk - 1 signaling . 0 ###LEFT-WALL### 1 rhes 0 ###LEFT-WALL### 3 binds 1 rhes 3 binds 2 robustly 3 binds 3 binds 19 independent 4 the 19 independent 5 autophagy 19 independent 6 regulator 19 independent 7 beclin 9 1 7 beclin 11 decreasing 7 beclin 19 independent 8 - 9 1 9 1 10 , 10 , 11 decreasing 11 decreasing 14 interaction 11 decreasing 15 with 11 decreasing 17 - 12 its 14 interaction 13 inhibitory 14 interaction 15 with 16 bcl 18 2 19 independent 19 independent 20 of 19 independent 23 1 20 of 21 jnk 22 - 23 1 23 1 24 signaling 23 1 25 . finally , co - expression of mhtt blocks rhes - induced autophagy activation . 0 ###LEFT-WALL### 5 expression 0 ###LEFT-WALL### 8 blocks 0 ###LEFT-WALL### 10 - 0 ###LEFT-WALL### 14 . 1 finally 2 , 1 finally 5 expression 3 co 4 - 3 co 5 expression 5 expression 6 of 5 expression 8 blocks 6 of 7 mhtt 8 blocks 9 rhes 10 - 13 activation 11 induced 13 activation 12 autophagy 13 activation thus , the isolated pathology and delayed onset of hd may reflect the striatal - selective expression and changes in autophagic activity of rhes . 0 ###LEFT-WALL### 6 and 0 ###LEFT-WALL### 18 and 0 ###LEFT-WALL### 25 . 1 thus 2 , 1 thus 6 and 3 the 5 pathology 4 isolated 5 pathology 5 pathology 6 and 6 and 8 onset 6 and 9 of 6 and 18 and 7 delayed 8 onset 9 of 10 hd 11 may 12 reflect 11 may 18 and 12 reflect 17 expression 13 the 17 expression 14 striatal 15 - 14 striatal 17 expression 16 selective 17 expression 18 and 19 changes 18 and 20 in 20 in 22 activity 21 autophagic 22 activity 22 activity 23 of 23 of 24 rhes apolipoprotein e4 ( apoe4 ) allele is the major genetic risk factor for sporadic alzheimer disease ( ad ) due to the higher prevalence and earlier onset of ad in apoe4 carriers . 0 ###LEFT-WALL### 6 allele 0 ###LEFT-WALL### 7 is 0 ###LEFT-WALL### 33 . 1 apolipoprotein 2 e4 2 e4 4 apoe4 2 e4 6 allele 3 ( 4 apoe4 4 apoe4 5 ) 6 allele 7 is 7 is 12 factor 7 is 13 for 7 is 21 to 8 the 12 factor 9 major 12 factor 10 genetic 12 factor 11 risk 12 factor 13 for 16 disease 14 sporadic 16 disease 15 alzheimer 16 disease 16 disease 18 ad 17 ( 18 ad 18 ad 19 ) 20 due 21 to 21 to 25 and 22 the 24 prevalence 23 higher 24 prevalence 24 prevalence 25 and 25 and 27 onset 25 and 28 of 26 earlier 27 onset 28 of 29 ad 29 ad 30 in 30 in 32 carriers 31 apoe4 32 carriers accumulating data suggest that the interaction between the n - and the [c] [-] terminal domains in the protein may be the main pathologic feature of apoe4 . 0 ###LEFT-WALL### 2 data 0 ###LEFT-WALL### 3 suggest 0 ###LEFT-WALL### 28 . 1 accumulating 2 data 2 data 3 suggest 3 suggest 4 that 4 that 6 interaction 4 that 21 be 5 the 6 interaction 6 interaction 7 between 6 interaction 20 may 7 between 16 domains 8 the 16 domains 9 n 11 and 10 - 11 and 11 and 15 terminal 11 and 16 domains 12 the 15 terminal 16 domains 17 in 17 in 19 protein 18 the 19 protein 20 may 21 be 21 be 25 feature 22 the 23 main 22 the 25 feature 24 pathologic 25 feature 25 feature 26 of 26 of 27 apoe4 to test this hypothesis , we used arg - 61 mice , a model of apoe4 domain interaction , by introducing the domain interaction feature of human apoe4 into native mouse apoe . 0 ###LEFT-WALL### 1 to 0 ###LEFT-WALL### 2 test 0 ###LEFT-WALL### 5 , 0 ###LEFT-WALL### 33 . 1 to 2 test 2 test 4 hypothesis 3 this 4 hypothesis 5 , 6 we 5 , 7 used 6 we 7 used 7 used 8 arg 7 used 20 by 8 arg 11 mice 8 arg 14 model 9 - 11 mice 10 61 11 mice 11 mice 12 , 12 , 14 model 13 a 14 model 14 model 15 of 14 model 19 , 15 of 18 interaction 16 apoe4 17 domain 17 domain 18 interaction 20 by 21 introducing 21 introducing 25 feature 21 introducing 29 into 22 the 25 feature 23 domain 25 feature 24 interaction 25 feature 25 feature 26 of 26 of 28 apoe4 27 human 28 apoe4 29 into 32 apoe 30 native 31 mouse 31 mouse 32 apoe we carried out hippocampus - dependent learning and memory tests and related cellular and molecular assays on 12 - and 3 [-] month [-] old arg - 61 and age - matched background c57bl/6j mice . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 carried 1 we 2 carried 2 carried 4 hippocampus 3 out 4 hippocampus 4 hippocampus 8 and 5 - 8 and 6 dependent 7 learning 7 learning 8 and 8 and 35 mice 8 and 36 . 9 memory 11 and 9 memory 29 and 10 tests 11 and 11 and 12 related 11 and 28 61 12 related 14 and 12 related 20 and 13 cellular 14 and 14 and 15 molecular 16 assays 17 on 16 assays 20 and 17 on 18 12 19 - 20 and 20 and 26 arg 21 3 23 month 23 month 26 arg 25 old 26 arg 27 - 28 61 29 and 30 age 29 and 31 - 29 and 32 matched 32 matched 35 mice 33 background 35 mice 34 c57bl/6j 35 mice learning and memory task performance were impaired in arg - 61 mice at both old and young ages compared with c57bl/6j mice . 0 ###LEFT-WALL### 5 performance 0 ###LEFT-WALL### 7 impaired 0 ###LEFT-WALL### 10 - 0 ###LEFT-WALL### 23 . 1 learning 2 and 2 and 3 memory 2 and 5 performance 4 task 5 performance 5 performance 6 were 6 were 7 impaired 7 impaired 8 in 8 in 9 arg 10 - 12 mice 10 - 19 compared 11 61 12 mice 12 mice 13 at 12 mice 19 compared 13 at 18 ages 14 both 18 ages 15 old 16 and 16 and 17 young 16 and 18 ages 19 compared 20 with 19 compared 22 mice 20 with 21 c57bl/6j surprisingly , young arg - 61 mice had more mitotic doublecortin - positive cells in the subgranular zone ; mrna levels of brain - derived neurotrophic factor [(] bdnf ) and trkb were also higher in 3 - month [-] old arg - 61 hippocampus compared with c57bl/6j mice . 0 ###LEFT-WALL### 7 mice 0 ###LEFT-WALL### 8 had 0 ###LEFT-WALL### 12 - 1 surprisingly 2 , 1 surprisingly 7 mice 3 young 7 mice 4 arg 5 - 4 arg 7 mice 6 61 7 mice 7 mice 8 had 8 had 11 doublecortin 9 more 10 mitotic 10 mitotic 11 doublecortin 12 - 14 cells 12 - 19 ; 13 positive 14 cells 14 cells 15 in 15 in 18 zone 16 the 18 zone 17 subgranular 18 zone 19 ; 20 mrna 19 ; 33 were 20 mrna 33 were 21 levels 22 of 21 levels 31 and 22 of 23 brain 23 brain 29 bdnf 24 - 29 bdnf 25 derived 27 factor 26 neurotrophic 27 factor 27 factor 29 bdnf 29 bdnf 30 ) 31 and 32 trkb 31 and 33 were 33 were 34 also 33 were 35 higher 35 higher 36 in 36 in 37 3 37 3 42 arg 38 - 42 arg 39 month 41 old 41 old 42 arg 42 arg 45 hippocampus 42 arg 50 . 43 - 45 hippocampus 44 61 45 hippocampus 45 hippocampus 46 compared 45 hippocampus 50 . 46 compared 47 with 47 with 49 mice 48 c57bl/6j 49 mice these [early] - age neurotrophic and neurogenic ( proliferative ) effects in the arg - 61 mouse may be an inadequate compensatory but eventually detrimental attempt by the system to " repair " itself . 0 ###LEFT-WALL### 1 these 0 ###LEFT-WALL### 3 - 0 ###LEFT-WALL### 19 be 0 ###LEFT-WALL### 35 . 3 - 4 age 4 age 6 and 4 age 19 be 5 neurotrophic 6 and 6 and 17 mouse 6 and 18 may 7 neurogenic 11 effects 7 neurogenic 15 - 7 neurogenic 17 mouse 8 ( 11 effects 9 proliferative 10 ) 9 proliferative 11 effects 11 effects 12 in 11 effects 15 - 12 in 14 arg 13 the 14 arg 16 61 17 mouse 18 may 19 be 19 be 26 attempt 20 an 21 inadequate 20 an 26 attempt 21 inadequate 26 attempt 22 compensatory 23 but 23 but 24 eventually 23 but 25 detrimental 23 but 26 attempt 26 attempt 27 by 26 attempt 30 to 26 attempt 32 repair 27 by 29 system 28 the 29 system 30 to 31 " 30 to 32 repair 32 repair 33 " 32 repair 34 itself this is supported by the higher cleaved caspase - 3 levels in the young animals that [not] only persisted , but increased in old age , and the lower levels of doublecortin at old age in the hippocampus of arg - 61 mice . 0 ###LEFT-WALL### 1 this 0 ###LEFT-WALL### 21 but 1 this 21 but 2 is 3 supported 2 is 21 but 3 supported 4 by 4 by 8 caspase 5 the 8 caspase 6 higher 8 caspase 7 cleaved 8 caspase 8 caspase 11 levels 9 - 11 levels 10 3 11 levels 11 levels 12 in 11 levels 20 , 12 in 15 animals 13 the 15 animals 14 young 15 animals 15 animals 16 that 15 animals 19 persisted 16 that 19 persisted 18 only 19 persisted 21 but 22 increased 22 increased 23 in 22 increased 33 at 22 increased 36 in 23 in 27 and 24 old 25 age 25 age 27 and 26 , 27 and 27 and 30 levels 27 and 31 of 28 the 30 levels 29 lower 30 levels 31 of 32 doublecortin 33 at 35 age 34 old 35 age 36 in 38 hippocampus 37 the 38 hippocampus 38 hippocampus 39 of 39 of 40 arg 40 arg 43 mice 41 - 43 mice 42 61 43 mice 43 mice 44 . these results are consistent with human apoe4 - dependent cognitive and neuro - pathologic changes , supporting the principal role of domain interaction in the pathologic effect of apoe4 . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 are 0 ###LEFT-WALL### 30 . 1 these 2 results 2 results 3 are 3 are 4 consistent 4 consistent 5 with 5 with 7 apoe4 5 with 17 supporting 6 human 7 apoe4 7 apoe4 15 changes 8 - 15 changes 9 dependent 15 changes 10 cognitive 11 and 11 and 12 neuro 11 and 13 - 11 and 15 changes 14 pathologic 15 changes 15 changes 16 , 17 supporting 20 role 18 the 20 role 19 principal 20 role 20 role 21 of 21 of 23 interaction 22 domain 23 interaction 23 interaction 24 in 24 in 27 effect 25 the 27 effect 26 pathologic 27 effect 27 effect 28 of 28 of 29 apoe4 domain interaction is , therefore , a viable therapeutic/prophylactic target for cognitive impairment and ad in apoe4 subjects . 0 ###LEFT-WALL### 2 interaction 0 ###LEFT-WALL### 3 is 0 ###LEFT-WALL### 19 . 1 domain 2 interaction 2 interaction 3 is 3 is 5 therefore 3 is 10 target 3 is 11 for 3 is 16 in 4 , 5 therefore 5 therefore 6 , 7 a 8 viable 7 a 10 target 8 viable 10 target 9 therapeutic/prophylactic 10 target 11 for 14 and 12 cognitive 13 impairment 13 impairment 14 and 14 and 15 ad 16 in 18 subjects 17 apoe4 18 subjects the autonomic nervous system plays a central role in both acute and chronic blood pressure regulation in humans . 0 ###LEFT-WALL### 4 system 0 ###LEFT-WALL### 5 plays 0 ###LEFT-WALL### 19 . 1 the 4 system 2 autonomic 4 system 3 nervous 4 system 4 system 5 plays 5 plays 8 role 5 plays 9 in 5 plays 17 in 6 a 7 central 6 a 8 role 7 central 8 role 9 in 12 and 10 both 12 and 11 acute 12 and 12 and 16 regulation 13 chronic 14 blood 14 blood 16 regulation 15 pressure 16 regulation 17 in 18 humans the activity of the sympathetic branch of the autonomic nervous system is positively associated with peripheral resistance , an important determinant of mean arterial pressure in men . 0 ###LEFT-WALL### 2 activity 0 ###LEFT-WALL### 14 associated 1 the 2 activity 2 activity 3 of 2 activity 12 is 3 of 6 branch 4 the 6 branch 5 sympathetic 6 branch 6 branch 7 of 7 of 11 system 8 the 11 system 9 autonomic 11 system 10 nervous 11 system 12 is 13 positively 12 is 14 associated 14 associated 15 with 15 with 17 resistance 16 peripheral 17 resistance 17 resistance 21 determinant 18 , 21 determinant 19 an 20 important 19 an 21 determinant 20 important 21 determinant 21 determinant 22 of 21 determinant 28 . 22 of 25 pressure 23 mean 25 pressure 24 arterial 25 pressure 25 pressure 26 in 26 in 27 men in contrast , there is no association between sympathetic nerve activity and peripheral resistance in women before [menopause] , [yet] a positive association [after] menopause . 0 ###LEFT-WALL### 4 there 0 ###LEFT-WALL### 5 is 1 in 2 contrast 1 in 3 , 1 in 4 there 4 there 5 is 5 is 7 association 6 no 7 association 7 association 8 between 7 association 15 in 8 between 12 and 9 sympathetic 10 nerve 10 nerve 11 activity 11 activity 12 and 12 and 14 resistance 13 peripheral 14 resistance 15 in 16 women 16 women 17 before 16 women 25 menopause 19 , 25 menopause 21 a 22 positive 21 a 25 menopause 22 positive 23 association 23 association 25 menopause 25 menopause 26 . we hypothesized that autonomic support of blood pressure is higher after menopause [in] women . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 hypothesized 0 ###LEFT-WALL### 15 . 1 we 2 hypothesized 2 hypothesized 3 that 3 that 5 support 3 that 9 is 4 autonomic 5 support 5 support 6 of 5 support 9 is 6 of 8 pressure 7 blood 8 pressure 9 is 10 higher 10 higher 11 after 11 after 14 women 12 menopause 14 women the women were studied before and during autonomic blockade using trimethaphan camsylate . 0 ###LEFT-WALL### 2 women 0 ###LEFT-WALL### 4 studied 0 ###LEFT-WALL### 13 . 1 the 2 women 2 women 3 were 3 were 4 studied 4 studied 6 and 5 before 6 and 6 and 7 during 7 during 12 camsylate 8 autonomic 9 blockade 9 blockade 12 camsylate 10 using 12 camsylate 11 trimethaphan 12 camsylate at baseline , muscle sympathetic nerve activity burst frequency and burst incidence were higher in the older women ( 33±3 versus 15±1 [bursts/min] [;] 57±5 versus 25±2 bursts/100 heartbeats , respectively ; p<0.05 [ )( 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 13 were 0 ###LEFT-WALL### 32 ; 0 ###LEFT-WALL### 35 )( 1 at 2 baseline 1 at 3 , 1 at 10 and 4 muscle 9 frequency 5 sympathetic 6 nerve 6 nerve 9 frequency 7 activity 8 burst 8 burst 9 frequency 9 frequency 10 and 10 and 12 incidence 10 and 13 were 11 burst 12 incidence 13 were 14 higher 14 higher 15 in 14 higher 31 respectively 15 in 18 women 16 the 18 women 17 older 18 women 18 women 20 33±3 19 ( 20 33±3 20 33±3 21 versus 20 33±3 30 , 21 versus 25 57±5 22 15±1 25 57±5 25 57±5 26 versus 26 versus 29 heartbeats 27 25±2 29 heartbeats 28 bursts/100 29 heartbeats 30 , 31 respectively 31 respectively 32 ; 32 ; 33 p<0.05 muscle sympathetic nerve activity bursts were abolished by trimethaphan within minutes . 0 ###LEFT-WALL### 5 bursts 0 ###LEFT-WALL### 7 abolished 0 ###LEFT-WALL### 12 . 1 muscle 5 bursts 2 sympathetic 3 nerve 3 nerve 5 bursts 4 activity 5 bursts 5 bursts 6 were 6 were 7 abolished 7 abolished 8 by 7 abolished 10 within 8 by 9 trimethaphan 10 within 11 minutes older women had a greater decrease in mean arterial pressure [(] - 29±2 [versus] - 9±2 [mm] [hg] ; p<0.01 ) [and] total peripheral resistance ( [-] 10±1 [versus] - 5±1 [mm] [hg/l] per minute [;] [p<0.01] [ )(during trimethaphan . 0 ###LEFT-WALL### 2 women 0 ###LEFT-WALL### 3 had 0 ###LEFT-WALL### 12 - 1 older 2 women 2 women 3 had 3 had 6 decrease 3 had 7 in 4 a 6 decrease 5 greater 6 decrease 7 in 10 pressure 8 mean 10 pressure 9 arterial 10 pressure 12 - 13 29±2 12 - 15 - 12 - 16 9±2 12 - 19 ; 15 - 16 9±2 19 ; 23 total 20 p<0.01 21 ) 20 p<0.01 23 total 23 total 25 resistance 24 peripheral 25 resistance 25 resistance 28 10±1 25 resistance 31 5±1 26 ( 28 10±1 28 10±1 30 - 30 - 31 5±1 31 5±1 34 per 31 5±1 39 )(during 31 5±1 41 . 34 per 35 minute 39 )(during 40 trimethaphan baseline muscle sympathetic nerve activity was associated with the decrease in mean arterial pressure during trimethaphan ( r= - 0.74 [;] p<0.05 ) . 0 ###LEFT-WALL### 5 activity 0 ###LEFT-WALL### 7 associated 0 ###LEFT-WALL### 24 . 1 baseline 2 muscle 2 muscle 5 activity 3 sympathetic 4 nerve 4 nerve 5 activity 5 activity 6 was 6 was 7 associated 7 associated 8 with 7 associated 11 in 8 with 10 decrease 9 the 10 decrease 11 in 14 pressure 12 mean 14 pressure 13 arterial 14 pressure 14 pressure 15 during 15 during 16 trimethaphan 16 trimethaphan 18 r= 17 ( 18 r= 18 r= 22 p<0.05 18 r= 23 ) 19 - 22 p<0.05 20 0.74 22 p<0.05 22 p<0.05 23 ) in summary , our results suggest that autonomic support of blood pressure is greater in older women compared with young women and that elevated sympathetic nerve activity in older women contributes importantly to the increased incidence [of] hypertension [after] menopause . 0 ###LEFT-WALL### 2 summary 0 ###LEFT-WALL### 3 , 0 ###LEFT-WALL### 41 . 1 in 2 summary 3 , 5 results 3 , 6 suggest 4 our 5 results 5 results 6 suggest 6 suggest 7 that 7 that 9 support 7 that 13 is 8 autonomic 9 support 9 support 10 of 9 support 13 is 10 of 12 pressure 11 blood 12 pressure 13 is 14 greater 14 greater 15 in 15 in 17 women 16 older 17 women 17 women 18 compared 18 compared 19 with 19 with 22 and 19 with 32 importantly 19 with 33 to 20 young 21 women 21 women 22 and 22 and 26 nerve 22 and 27 activity 22 and 31 contributes 23 that 24 elevated 24 elevated 26 nerve 25 sympathetic 26 nerve 27 activity 28 in 27 activity 31 contributes 28 in 30 women 29 older 30 women 33 to 40 menopause 34 the 40 menopause 35 increased 36 incidence 36 incidence 40 menopause 38 hypertension 40 menopause microtubules are key cytoskeletal elements found in all eukaryotic cells . 0 ###LEFT-WALL### 1 microtubules 0 ###LEFT-WALL### 3 key 0 ###LEFT-WALL### 11 . 1 microtubules 2 are 2 are 3 key 3 key 5 elements 4 cytoskeletal 5 elements 5 elements 6 found 6 found 7 in 7 in 10 cells 8 all 10 cells 9 eukaryotic 10 cells tau was identified as microtubule associated protein and was implicated in microtubule initiation as well [as] [assembly] . 0 ###LEFT-WALL### 1 tau 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 18 . 1 tau 8 and 2 was 3 identified 2 was 8 and 3 identified 4 as 4 as 5 microtubule 4 as 6 associated 5 microtubule 6 associated 6 associated 7 protein 8 and 9 was 8 and 15 well 9 was 10 implicated 10 implicated 11 in 11 in 13 initiation 12 microtubule 13 initiation 14 as 15 well its expression is increased expression in neurons and has a specific association with axonal microtubules . 0 ###LEFT-WALL### 2 expression 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 16 . 1 its 2 expression 2 expression 8 and 3 is 5 expression 3 is 8 and 4 increased 5 expression 5 expression 6 in 6 in 7 neurons 8 and 9 has 8 and 12 association 10 a 11 specific 10 a 12 association 11 specific 12 association 12 association 13 with 13 with 15 microtubules 14 axonal 15 microtubules neurodegenerative disorders associated with abundant tau inclusions are collectively described as tauopathies . 0 ###LEFT-WALL### 2 disorders 0 ###LEFT-WALL### 10 described 0 ###LEFT-WALL### 13 . 1 neurodegenerative 2 disorders 2 disorders 3 associated 2 disorders 8 are 3 associated 4 with 4 with 7 inclusions 5 abundant 6 tau 6 tau 7 inclusions 8 are 10 described 9 collectively 10 described 10 described 11 as 11 as 12 tauopathies pathological inclusions in neurons and glial cells containing fibrillary aggregates of abnormally hyperphosphorylated tau protein are characteristic features of tauopathies . 0 ###LEFT-WALL### 1 pathological 0 ###LEFT-WALL### 2 inclusions 0 ###LEFT-WALL### 5 and 0 ###LEFT-WALL### 21 . 1 pathological 2 inclusions 2 inclusions 3 in 3 in 4 neurons 5 and 7 cells 5 and 16 are 6 glial 7 cells 7 cells 8 containing 7 cells 16 are 8 containing 10 aggregates 9 fibrillary 10 aggregates 10 aggregates 11 of 11 of 15 protein 12 abnormally 13 hyperphosphorylated 13 hyperphosphorylated 15 protein 14 tau 15 protein 16 are 18 features 17 characteristic 18 features 18 features 19 of 19 of 20 tauopathies we outlined the pathological features of major tauopathies , including neurofibrillary tangle formation diseases , pick 's disease ( pid ) , progressive supranuclear palsy ( psp ) , corticobasal degeneration ( cbd ) , and argyrophilic grain disease ( agd ) . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 outlined 0 ###LEFT-WALL### 43 . 1 we 2 outlined 2 outlined 36 and 3 the 5 features 4 pathological 5 features 5 features 6 of 5 features 36 and 6 of 8 tauopathies 7 major 8 tauopathies 8 tauopathies 10 including 8 tauopathies 18 disease 9 , 10 including 10 including 14 diseases 10 including 15 , 11 neurofibrillary 12 tangle 12 tangle 14 diseases 13 formation 14 diseases 15 , 18 disease 16 pick 17 's 17 's 18 disease 18 disease 20 pid 18 disease 25 palsy 18 disease 35 , 19 ( 20 pid 20 pid 21 ) 22 , 25 palsy 23 progressive 25 palsy 24 supranuclear 25 palsy 25 palsy 27 psp 25 palsy 31 degeneration 25 palsy 35 , 26 ( 27 psp 27 psp 28 ) 29 , 31 degeneration 30 corticobasal 31 degeneration 31 degeneration 33 cbd 31 degeneration 34 ) 32 ( 33 cbd 33 cbd 34 ) 36 and 39 disease 36 and 41 agd 37 argyrophilic 39 disease 38 grain 39 disease 40 ( 41 agd 41 agd 42 ) disease specific isoform compositions of tau are identified in these tauopathies . 0 ###LEFT-WALL### 4 compositions 0 ###LEFT-WALL### 8 identified 0 ###LEFT-WALL### 12 . 1 disease 4 compositions 2 specific 3 isoform 3 isoform 4 compositions 4 compositions 5 of 4 compositions 7 are 5 of 6 tau 7 are 8 identified 8 identified 9 in 9 in 11 tauopathies 10 these 11 tauopathies neurofibrillary [tangles] ( nfts ) in alzheimer 's disease [contain] both [three] repeat ( 3r ) - and four repeat ( 4r ) - tau . 0 ###LEFT-WALL### 18 and 0 ###LEFT-WALL### 24 - 0 ###LEFT-WALL### 26 . 1 neurofibrillary 4 nfts 1 neurofibrillary 6 in 1 neurofibrillary 18 and 3 ( 4 nfts 4 nfts 5 ) 6 in 9 disease 7 alzheimer 8 's 8 's 9 disease 9 disease 11 both 9 disease 13 repeat 9 disease 15 3r 11 both 13 repeat 14 ( 15 3r 15 3r 16 ) 17 - 18 and 18 and 20 repeat 18 and 22 4r 19 four 20 repeat 21 ( 22 4r 22 4r 23 ) 24 - 25 tau pick bodies in pid are immunopositive for 3r - tau . 0 ###LEFT-WALL### 2 bodies 0 ###LEFT-WALL### 5 are 0 ###LEFT-WALL### 11 . 1 pick 2 bodies 2 bodies 3 in 2 bodies 5 are 3 in 4 pid 5 are 6 immunopositive 6 immunopositive 7 for 7 for 10 tau 8 3r 9 - 8 3r 10 tau in psp nfts , tufted astrocytes , coiled bodies and threads contain 4r - tau and in cbd , pretangles , astrocytic plaques , coiled bodies and threads also demonstrate 4r - tau . 0 ###LEFT-WALL### 27 and 0 ###LEFT-WALL### 30 demonstrate 0 ###LEFT-WALL### 34 . 1 in 2 psp 1 in 16 and 2 psp 10 and 2 psp 12 contain 3 nfts 4 , 4 , 6 astrocytes 4 , 7 , 5 tufted 6 astrocytes 7 , 9 bodies 7 , 10 and 8 coiled 9 bodies 10 and 11 threads 10 and 12 contain 12 contain 15 tau 13 4r 14 - 13 4r 15 tau 16 and 17 in 16 and 21 , 16 and 27 and 17 in 18 cbd 18 cbd 20 pretangles 19 , 20 pretangles 20 pretangles 21 , 22 astrocytic 23 plaques 23 plaques 24 , 24 , 26 bodies 24 , 27 and 25 coiled 26 bodies 27 and 28 threads 27 and 30 demonstrate 29 also 30 demonstrate 30 demonstrate 33 tau 31 4r 32 - 31 4r 33 tau argyrophilic grains are immunopositive for 4r - tau . 0 ###LEFT-WALL### 2 grains 0 ###LEFT-WALL### 3 are 0 ###LEFT-WALL### 9 . 1 argyrophilic 2 grains 2 grains 3 are 3 are 4 immunopositive 4 immunopositive 5 for 5 for 8 tau 6 4r 7 - 6 4r 8 tau although psp and cbd sometimes share certain pathological distribution , which makes clinical diagnosis difficult , cellular tau pathology and aggregation patterns in neurons and glia are different between the two diseases . 0 ###LEFT-WALL### 6 share 0 ###LEFT-WALL### 10 , 0 ###LEFT-WALL### 33 . 1 although 4 cbd 1 although 6 share 2 psp 3 and 3 and 4 cbd 5 sometimes 6 share 6 share 9 distribution 7 certain 9 distribution 8 pathological 9 distribution 10 , 11 which 10 , 12 makes 11 which 12 makes 12 makes 14 diagnosis 12 makes 20 and 13 clinical 14 diagnosis 15 difficult 16 , 16 , 19 pathology 16 , 20 and 17 cellular 19 pathology 18 tau 19 pathology 20 and 21 aggregation 20 and 22 patterns 20 and 27 are 20 and 28 different 22 patterns 23 in 22 patterns 27 are 23 in 25 and 24 neurons 25 and 25 and 26 glia 28 different 29 between 29 between 32 diseases 30 the 31 two 31 two 32 diseases master athletes are more than 35 years [of] age and continue to train as hard as their young counterparts despite the aging process . 0 ###LEFT-WALL### 2 athletes 0 ###LEFT-WALL### 3 are 0 ###LEFT-WALL### 5 than 0 ###LEFT-WALL### 24 . 1 master 2 athletes 2 athletes 3 are 3 are 4 more 3 are 5 than 5 than 7 years 5 than 10 and 6 35 7 years 7 years 10 and 9 age 10 and 10 and 11 continue 11 continue 12 to 12 to 13 train 13 train 15 hard 13 train 16 as 13 train 20 despite 13 train 23 process 14 as 15 hard 16 as 19 counterparts 17 their 19 counterparts 18 young 19 counterparts 20 despite 22 aging 21 the 22 aging all [life] long , they are capable of accomplishing exceptional sporting performances . 0 ###LEFT-WALL### 1 all 0 ###LEFT-WALL### 3 long 0 ###LEFT-WALL### 4 , 0 ###LEFT-WALL### 13 . 1 all 3 long 4 , 5 they 4 , 6 are 5 they 6 are 6 are 7 capable 7 capable 8 of 8 of 9 accomplishing 9 accomplishing 12 performances 10 exceptional 12 performances 11 sporting 12 performances for these participants in endurance events , matching energy intake and expenditure is critical to maintain health and performance . 0 ###LEFT-WALL### 8 matching 0 ###LEFT-WALL### 13 is 0 ###LEFT-WALL### 20 . 1 for 3 participants 1 for 7 , 1 for 8 matching 2 these 3 participants 3 participants 4 in 4 in 6 events 5 endurance 6 events 8 matching 11 and 8 matching 13 is 9 energy 10 intake 10 intake 11 and 11 and 12 expenditure 13 is 14 critical 14 critical 15 to 15 to 16 maintain 16 maintain 18 and 17 health 18 and 18 and 19 performance the proportions of carbohydrate , fat , and protein must be optimized to provide enough calories to [sustain] the energy requirements of competition or training , and for recovery . 0 ###LEFT-WALL### 2 proportions 0 ###LEFT-WALL### 14 provide 0 ###LEFT-WALL### 30 . 1 the 2 proportions 2 proportions 3 of 2 proportions 10 must 3 of 8 and 4 carbohydrate 5 , 5 , 6 fat 5 , 8 and 7 , 8 and 8 and 9 protein 10 must 11 be 11 be 12 optimized 12 optimized 13 to 13 to 14 provide 14 provide 16 calories 14 provide 27 and 15 enough 16 calories 17 to 24 or 17 to 27 and 19 the 21 requirements 20 energy 21 requirements 21 requirements 22 of 21 requirements 24 or 22 of 23 competition 24 or 25 training 26 , 27 and 27 and 28 for 28 for 29 recovery in addition , endurance athletes [must] include adequate vitamins and minerals in their diets to maintain healthy immune function . 0 ###LEFT-WALL### 19 function 0 ###LEFT-WALL### 20 . 1 in 2 addition 2 addition 3 , 3 , 9 vitamins 3 , 10 and 4 endurance 9 vitamins 5 athletes 9 vitamins 7 include 9 vitamins 8 adequate 9 vitamins 10 and 11 minerals 10 and 12 in 10 and 19 function 12 in 14 diets 13 their 14 diets 14 diets 15 to 14 diets 16 maintain 15 to 16 maintain 17 healthy 19 function 18 immune 19 function vitamins and minerals may be sufficient in the diets of endurance athletes , who have a high energy intake . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 5 be 0 ###LEFT-WALL### 13 , 0 ###LEFT-WALL### 20 . 1 vitamins 2 and 2 and 3 minerals 2 and 4 may 4 may 5 be 5 be 6 sufficient 6 sufficient 7 in 7 in 9 diets 8 the 9 diets 9 diets 10 of 10 of 12 athletes 11 endurance 12 athletes 13 , 14 who 13 , 15 have 14 who 15 have 15 have 19 intake 16 a 17 high 16 a 19 intake 17 high 18 energy 18 energy 19 intake this would make it unnecessary to use vitamin [and] mineral supplements . 0 ###LEFT-WALL### 1 this 0 ###LEFT-WALL### 3 make 0 ###LEFT-WALL### 12 . 1 this 2 would 2 would 3 make 3 make 4 it 3 make 5 unnecessary 5 unnecessary 6 to 5 unnecessary 7 use 6 to 7 use 7 use 11 supplements 8 vitamin 11 supplements 10 mineral 11 supplements furthermore , one major limitation for these athletes is the management of oxidative stress , which , when in excess , can be deleterious for the organism . 0 ###LEFT-WALL### 5 limitation 0 ###LEFT-WALL### 9 is 0 ###LEFT-WALL### 15 , 0 ###LEFT-WALL### 28 . 1 furthermore 2 , 1 furthermore 5 limitation 3 one 5 limitation 4 major 5 limitation 5 limitation 6 for 5 limitation 9 is 6 for 8 athletes 7 these 8 athletes 9 is 11 management 10 the 11 management 11 management 12 of 12 of 14 stress 13 oxidative 14 stress 15 , 16 which 15 , 23 be 16 which 22 can 17 , 18 when 18 when 19 in 18 when 21 , 18 when 22 can 19 in 20 excess 22 can 23 be 23 be 24 deleterious 24 deleterious 25 for 25 for 27 organism 26 the 27 organism for individuals exposed to oxidative stress , micronutritional supplementations rich in vitamins and minerals can be also an alternative strategy . 0 ###LEFT-WALL### 9 supplementations 0 ###LEFT-WALL### 16 be 0 ###LEFT-WALL### 21 . 1 for 2 individuals 1 for 7 , 1 for 9 supplementations 2 individuals 3 exposed 3 exposed 4 to 4 to 6 stress 5 oxidative 6 stress 8 micronutritional 9 supplementations 9 supplementations 10 rich 9 supplementations 15 can 10 rich 11 in 11 in 13 and 12 vitamins 13 and 13 and 14 minerals 15 can 16 be 16 be 17 also 16 be 20 strategy 18 an 19 alternative 18 an 20 strategy 19 alternative 20 strategy although these supplementations are increasingly used by master athletes , very few data are available on their effects on oxidative stress , muscle recovery , and physical performance . 0 ###LEFT-WALL### 13 data 0 ###LEFT-WALL### 14 are 0 ###LEFT-WALL### 29 . 1 although 3 supplementations 1 although 6 used 1 although 10 , 1 although 13 data 2 these 3 supplementations 3 supplementations 4 are 4 are 6 used 5 increasingly 6 used 6 used 7 by 7 by 9 athletes 8 master 9 athletes 11 very 12 few 12 few 13 data 13 data 14 are 14 are 15 available 15 available 16 on 15 available 19 on 16 on 18 effects 17 their 18 effects 19 on 26 and 20 oxidative 21 stress 21 stress 22 , 22 , 24 recovery 22 , 26 and 23 muscle 24 recovery 25 , 26 and 26 and 28 performance 27 physical 28 performance the potential benefits of supplement use in athletes are thus questionable . 0 ###LEFT-WALL### 3 benefits 0 ###LEFT-WALL### 9 are 0 ###LEFT-WALL### 12 . 1 the 3 benefits 2 potential 3 benefits 3 benefits 4 of 3 benefits 9 are 4 of 6 use 5 supplement 6 use 6 use 7 in 7 in 8 athletes 9 are 10 thus 9 are 11 questionable some studies indicate no benefits , while others highlight potential negative side effects of vitamin supplementation . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 3 indicate 1 some 2 studies 2 studies 3 indicate 3 indicate 5 benefits 3 indicate 7 while 4 no 5 benefits 6 , 7 while 7 while 8 others 7 while 9 highlight 7 while 17 . 8 others 9 highlight 9 highlight 13 effects 10 potential 11 negative 11 negative 13 effects 12 side 13 effects 13 effects 14 of 14 of 16 supplementation 15 vitamin 16 supplementation additional studies are warranted in order to design adapted prescriptions in antioxidant vitamins and minerals . 0 ###LEFT-WALL### 1 additional 0 ###LEFT-WALL### 9 adapted 0 ###LEFT-WALL### 16 . 1 additional 2 studies 1 additional 8 design 1 additional 9 adapted 2 studies 3 are 3 are 4 warranted 4 warranted 5 in 5 in 6 order 6 order 7 to 6 order 8 design 7 to 8 design 9 adapted 10 prescriptions 9 adapted 11 in 11 in 14 and 12 antioxidant 13 vitamins 13 vitamins 14 and 14 and 15 minerals background : few data are available for patients with a late onset ( ≥ 50 years ) of neuromyelitis optica ( lonmo ) or neuromyelitis optica spectrum disease ( lonmosd ) , defined by [an] optic neuritis/longitudinally extensive transverse myelitis with aquaporin - 4 antibodies ( aqp4 - ab ) . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 51 . 2 : 4 data 2 : 5 are 2 : 24 or 3 few 4 data 4 data 5 are 5 are 6 available 6 available 7 for 7 for 8 patients 8 patients 9 with 8 patients 18 of 8 patients 22 lonmo 9 with 12 onset 10 a 12 onset 11 late 12 onset 12 onset 16 years 13 ( 16 years 14 ≥ 16 years 15 50 16 years 16 years 17 ) 18 of 20 optica 19 neuromyelitis 20 optica 21 ( 22 lonmo 22 lonmo 23 ) 24 or 25 neuromyelitis 24 or 26 optica 25 neuromyelitis 26 optica 26 optica 28 disease 26 optica 33 defined 27 spectrum 28 disease 28 disease 30 lonmosd 29 ( 30 lonmosd 30 lonmosd 31 ) 32 , 33 defined 33 defined 34 by 33 defined 50 ) 34 by 40 myelitis 36 optic 40 myelitis 37 neuritis/longitudinally 38 extensive 38 extensive 40 myelitis 39 transverse 40 myelitis 40 myelitis 41 with 41 with 42 aquaporin 42 aquaporin 45 antibodies 43 - 45 antibodies 44 4 45 antibodies 45 antibodies 47 aqp4 45 antibodies 50 ) 46 ( 47 aqp4 47 aqp4 49 ab 47 aqp4 50 ) 48 - 49 ab 49 ab 50 ) objective : to characterize lonmo and lonmosd , and to analyze their predictive factors of disability and death . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 19 . 1 objective 2 : 2 : 3 to 2 : 9 and 3 to 9 and 4 characterize 7 lonmosd 4 characterize 9 and 5 lonmo 6 and 6 and 7 lonmosd 8 , 9 and 9 and 10 to 9 and 11 analyze 10 to 11 analyze 11 analyze 14 factors 12 their 14 factors 13 predictive 14 factors 14 factors 15 of 15 of 17 and 16 disability 17 and 17 and 18 death methods : we identified 430 patients from four cohorts of nmo/nmosd in france , germany , turkey and uk . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 3 we 2 : 4 identified 2 : 20 . 3 we 4 identified 4 identified 6 patients 4 identified 12 in 5 430 6 patients 6 patients 7 from 7 from 9 cohorts 8 four 9 cohorts 9 cohorts 10 of 10 of 11 nmo/nmosd 12 in 18 and 13 france 14 , 14 , 15 germany 14 , 16 , 16 , 17 turkey 16 , 18 and 18 and 19 uk we extracted the late onset patients and analyzed them for predictive factors of disability and death , using the cox proportional model . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 7 and 0 ###LEFT-WALL### 23 . 1 we 7 and 2 extracted 6 patients 2 extracted 7 and 3 the 6 patients 4 late 5 onset 5 onset 6 patients 7 and 8 analyzed 8 analyzed 9 them 8 analyzed 10 for 10 for 12 factors 11 predictive 12 factors 12 factors 13 of 13 of 15 and 14 disability 15 and 15 and 16 death 15 and 17 , 15 and 18 using 18 using 22 model 19 the 22 model 20 cox 22 model 21 proportional 22 model results : we followed up on 63 patients with lonmo and [45] with lonmosd during a mean of 4.6 years . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 21 . 2 : 3 we 2 : 4 followed 3 we 4 followed 4 followed 5 up 4 followed 6 on 4 followed 11 and 6 on 8 patients 7 63 8 patients 9 with 10 lonmo 9 with 11 and 11 and 13 with 13 with 14 lonmosd 14 lonmosd 15 during 14 lonmosd 18 of 15 during 17 mean 16 a 17 mean 18 of 20 years 19 4.6 20 years this lonmo/lonmosd cohort was mainly of caucasian origin ( 93 % ) , women ( 80 % ) , seropositive for aqp4 - ab ( 85 % ) and from 50 to 82.5 years of age [at] onset . 0 ###LEFT-WALL### 3 cohort 0 ###LEFT-WALL### 4 was 0 ###LEFT-WALL### 23 - 1 this 3 cohort 2 lonmo/lonmosd 3 cohort 3 cohort 4 was 4 was 5 mainly 4 was 6 of 6 of 8 origin 7 caucasian 8 origin 8 origin 11 % 8 origin 14 women 8 origin 20 seropositive 9 ( 11 % 10 93 11 % 11 % 12 ) 13 , 14 women 14 women 17 % 14 women 19 , 15 ( 17 % 16 80 17 % 17 % 18 ) 19 , 20 seropositive 20 seropositive 21 for 20 seropositive 23 - 21 for 22 aqp4 23 - 38 onset 23 - 39 . 24 ab 27 % 24 ab 29 and 25 ( 27 % 26 85 27 % 27 % 28 ) 29 and 34 years 29 and 35 of 29 and 38 onset 30 from 32 to 31 50 32 to 32 to 33 82.5 32 to 34 years 35 of 36 age no progressive course was noted . 0 ###LEFT-WALL### 3 course 0 ###LEFT-WALL### 5 noted 0 ###LEFT-WALL### 6 . 1 no 3 course 2 progressive 3 course 3 course 4 was 4 was 5 noted at last follow - up , the median expanded disability status scale ( edss ) scores were 5.5 and 6 in the lonmo and lonmosd groups , respectively . 0 ###LEFT-WALL### 3 follow 0 ###LEFT-WALL### 6 , 0 ###LEFT-WALL### 29 . 1 at 2 last 1 at 3 follow 3 follow 5 up 4 - 5 up 5 up 6 , 6 , 16 scores 6 , 17 were 7 the 16 scores 8 median 16 scores 9 expanded 10 disability 10 disability 11 status 11 status 12 scale 12 scale 14 edss 13 ( 14 edss 14 edss 15 ) 14 edss 16 scores 16 scores 17 were 17 were 19 and 17 were 28 respectively 18 5.5 19 and 19 and 20 6 19 and 21 in 21 in 24 and 22 the 23 lonmo 23 lonmo 24 and 24 and 26 groups 24 and 27 , 25 lonmosd 26 groups outcome was mainly characterized by motor disability and relatively good visual function . 0 ###LEFT-WALL### 1 outcome 0 ###LEFT-WALL### 4 characterized 0 ###LEFT-WALL### 13 . 1 outcome 2 was 2 was 4 characterized 3 mainly 4 characterized 4 characterized 5 by 5 by 8 and 6 motor 7 disability 7 disability 8 and 8 and 12 function 9 relatively 10 good 10 good 12 function 11 visual 12 function at last follow - up , 14 patients had died , including seven ( 50 % ) due to acute myelitis [and] six ( 43 % ) because of opportunistic infections . 0 ###LEFT-WALL### 3 follow 0 ###LEFT-WALL### 6 , 0 ###LEFT-WALL### 32 . 1 at 2 last 1 at 3 follow 3 follow 5 up 4 - 5 up 5 up 6 , 6 , 8 patients 6 , 10 died 7 14 8 patients 8 patients 9 had 9 had 10 died 10 died 12 including 10 died 19 to 10 died 28 because 11 , 12 including 12 including 13 seven 12 including 17 ) 13 seven 16 % 14 ( 16 % 15 50 16 % 16 % 17 ) 18 due 19 to 19 to 21 myelitis 20 acute 21 myelitis 21 myelitis 23 six 21 myelitis 26 % 24 ( 26 % 25 43 26 % 26 % 27 ) 28 because 29 of 29 of 31 infections 30 opportunistic 31 infections the edss 4 score was independently predicted by an older age [at] onset , as a continuous variable after 50 years of age . 0 ###LEFT-WALL### 2 edss 0 ###LEFT-WALL### 7 predicted 1 the 2 edss 2 edss 3 4 2 edss 4 score 2 edss 5 was 3 4 4 score 5 was 7 predicted 6 independently 7 predicted 7 predicted 8 by 8 by 13 onset 9 an 13 onset 10 older 11 age 11 age 13 onset 13 onset 15 as 14 , 15 as 15 as 18 variable 15 as 24 . 16 a 17 continuous 16 a 18 variable 17 continuous 18 variable 18 variable 19 after 18 variable 22 of 19 after 21 years 20 50 21 years 22 of 23 age death was predicted by two independent factors : an older age [at] onset and a high annualized relapse rate . 0 ###LEFT-WALL### 1 death 0 ###LEFT-WALL### 3 predicted 0 ###LEFT-WALL### 8 : 1 death 2 was 2 was 3 predicted 3 predicted 4 by 4 by 7 factors 5 two 7 factors 6 independent 7 factors 8 : 14 and 8 : 19 rate 8 : 20 . 9 an 13 onset 10 older 11 age 11 age 13 onset 13 onset 14 and 14 and 18 relapse 14 and 19 rate 15 a 16 high 15 a 18 relapse 16 high 18 relapse 17 annualized 18 relapse conclusion : lonmo/lonmosd is particularly severe , with a high rate of motor impairment and death . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 3 lonmo/lonmosd 2 : 4 is 3 lonmo/lonmosd 4 is 4 is 6 severe 5 particularly 6 severe 6 severe 8 with 7 , 8 with 8 with 11 rate 8 with 17 . 9 a 10 high 9 a 11 rate 10 high 11 rate 11 rate 12 of 12 of 15 and 13 motor 14 impairment 14 impairment 15 and 15 and 16 death background : tumor necrosis factor ( tnf [ )(levels are associated with risk for heart failure ( hf ) . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 20 . 1 background 2 : 2 : 3 tumor 3 tumor 4 necrosis 3 tumor 5 factor 3 tumor 7 tnf 4 necrosis 5 factor 6 ( 7 tnf 7 tnf 9 )(levels 7 tnf 10 are 7 tnf 11 associated 7 tnf 12 with 7 tnf 14 for 7 tnf 19 ) 9 )(levels 10 are 12 with 13 risk 14 for 16 failure 15 heart 16 failure 16 failure 18 hf 17 ( 18 hf 18 hf 19 ) the soluble tnf type 1 ( stnf - r1 ) and type 2 ( stnf - r2 ) receptors are elevated in patients with manifest hf , but whether they are associated with risk for incident hf is unclear . 0 ###LEFT-WALL### 3 tnf 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 16 - 1 the 3 tnf 2 soluble 3 tnf 3 tnf 11 and 4 type 5 1 4 type 11 and 5 1 7 stnf 5 1 9 r1 6 ( 7 stnf 7 stnf 8 - 8 - 9 r1 9 r1 10 ) 11 and 12 type 12 type 13 2 13 2 15 stnf 14 ( 15 stnf 15 stnf 16 - 16 - 19 receptors 16 - 21 elevated 16 - 28 but 16 - 40 . 17 r2 18 ) 17 r2 19 receptors 19 receptors 20 are 20 are 21 elevated 21 elevated 22 in 21 elevated 24 with 22 in 23 patients 24 with 26 hf 25 manifest 26 hf 27 , 28 but 28 but 29 whether 28 but 38 is 29 whether 30 they 29 whether 32 associated 29 whether 38 is 30 they 31 are 31 are 32 associated 32 associated 33 with 33 with 34 risk 34 risk 35 for 35 for 37 hf 36 incident 37 hf 38 is 39 unclear methods and results : using cox proportional hazard models , we examined the association between baseline levels of stnf - r1 and stnf - r2 with incident hf risk among 1285 participants of the health , aging , and body composition study ( age , 74.0±2.9 years ; 51.4 % women ; 41.1 % black [ )( 0 ###LEFT-WALL### 3 results 0 ###LEFT-WALL### 4 : 1 methods 2 and 2 and 3 results 4 : 11 we 4 : 12 examined 4 : 20 - 4 : 24 - 5 using 9 models 5 using 10 , 5 using 11 we 6 cox 9 models 7 proportional 8 hazard 8 hazard 9 models 11 we 12 examined 12 examined 14 association 12 examined 15 between 13 the 14 association 15 between 17 levels 16 baseline 17 levels 17 levels 18 of 18 of 19 stnf 20 - 22 and 21 r1 22 and 22 and 23 stnf 24 - 39 and 24 - 48 ; 24 - 57 )( 25 r2 26 with 25 r2 33 of 25 r2 39 and 26 with 29 risk 27 incident 29 risk 28 hf 29 risk 29 risk 30 among 30 among 32 participants 31 1285 32 participants 33 of 35 health 34 the 35 health 35 health 37 aging 36 , 37 aging 37 aging 38 , 38 , 39 and 39 and 42 study 39 and 44 age 40 body 41 composition 41 composition 42 study 43 ( 44 age 44 age 47 years 44 age 48 ; 45 , 47 years 46 74.0±2.9 47 years 47 years 48 ; 48 ; 51 women 48 ; 52 ; 49 51.4 51 women 50 % 51 women 52 ; 55 black 53 41.1 54 % 54 % 55 black during a median follow - up of 11.4 ( 6.9 - 11.7 ) years , 233 ( 18.1 % ) participants developed hf . 0 ###LEFT-WALL### 4 follow 0 ###LEFT-WALL### 5 - 1 during 3 median 1 during 4 follow 2 a 3 median 5 - 21 participants 5 - 22 developed 5 - 24 . 6 up 21 participants 7 of 14 years 7 of 21 participants 8 11.4 14 years 9 ( 11 - 10 6.9 11 - 11 - 12 11.7 11 - 13 ) 11 - 14 years 14 years 16 233 15 , 16 233 16 233 19 % 16 233 20 ) 17 ( 19 % 18 18.1 19 % 19 % 20 ) 21 participants 22 developed 22 developed 23 hf these associations were consistent across whites and blacks ( tnf , stnf - r1 , stnf - r2 ; interaction [p=0.531] , 0.091 , and [0.795] , respectively ) [and] in both sexes ( tnf , stnf [-] r1 , stnf - r2 [;] interaction p=0.491 , 0.672 , [and] 0.999 , [respectively] ) . 0 ###LEFT-WALL### 2 associations 0 ###LEFT-WALL### 11 , 1 these 2 associations 2 associations 3 were 3 were 4 consistent 4 consistent 5 across 5 across 7 and 6 whites 7 and 7 and 8 blacks 7 and 10 tnf 9 ( 10 tnf 10 tnf 11 , 11 , 18 r2 11 , 19 ; 12 stnf 14 r1 12 stnf 18 r2 13 - 14 r1 14 r1 16 stnf 14 r1 17 - 15 , 16 stnf 16 stnf 17 - 19 ; 20 interaction 19 ; 22 , 22 , 23 0.091 22 , 25 and 24 , 25 and 25 and 27 , 25 and 28 respectively 25 and 33 sexes 25 and 37 stnf 27 , 28 respectively 28 respectively 29 ) 31 in 32 both 31 in 33 sexes 33 sexes 35 tnf 33 sexes 37 stnf 34 ( 35 tnf 35 tnf 36 , 37 stnf 39 r1 39 r1 41 stnf 39 r1 46 p=0.491 40 , 41 stnf 41 stnf 42 - 42 - 46 p=0.491 43 r2 45 interaction 45 interaction 46 p=0.491 46 p=0.491 48 0.672 46 p=0.491 55 . 47 , 48 0.672 48 0.672 51 0.999 48 0.672 54 ) 49 , 51 0.999 51 0.999 52 , tnf - r1 was associated with a higher risk for hf [with] preserved versus reduced ejection fraction ( hr , 1.81 [;] 95 % ci , 1.03 - 3.18 [;] p=0.038 for preserved [versus] hr , 0.90 [;] 95 % ci , 0.56 - 1.44 [;] p=0.667 for reduced ejection fraction [;] interaction p=0.05 [ )( 0 ###LEFT-WALL### 3 r1 0 ###LEFT-WALL### 5 associated 1 tnf 2 - 1 tnf 3 r1 3 r1 4 was 4 was 5 associated 5 associated 6 with 6 with 9 risk 6 with 17 fraction 7 a 9 risk 8 higher 9 risk 9 risk 10 for 9 risk 13 preserved 9 risk 14 versus 10 for 11 hf 14 versus 16 ejection 15 reduced 16 ejection 17 fraction 19 hr 17 fraction 25 ci 17 fraction 28 - 18 ( 19 hr 19 hr 20 , 20 , 25 ci 21 1.81 25 ci 23 95 25 ci 24 % 25 ci 25 ci 26 , 26 , 28 - 27 1.03 28 - 28 - 31 p=0.038 29 3.18 31 p=0.038 31 p=0.038 32 for 32 for 35 hr 33 preserved 35 hr 35 hr 41 ci 35 hr 47 p=0.667 36 , 41 ci 37 0.90 41 ci 39 95 41 ci 40 % 41 ci 41 ci 42 , 42 , 47 p=0.667 43 0.56 44 - 44 - 45 1.44 44 - 47 p=0.667 47 p=0.667 48 for 47 p=0.667 56 )( 48 for 54 p=0.05 49 reduced 53 interaction 50 ejection 53 interaction 51 fraction 53 interaction 53 interaction 54 p=0.05 conclusions : in older adults , elevated levels of stnf - r1 are associated with increased risk for incident hf . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 6 , 0 ###LEFT-WALL### 21 . 1 conclusions 2 : 2 : 3 in 3 in 5 adults 4 older 5 adults 6 , 8 levels 6 , 14 associated 7 elevated 8 levels 8 levels 9 of 8 levels 13 are 9 of 12 r1 10 stnf 11 - 10 stnf 12 r1 13 are 14 associated 14 associated 15 with 15 with 17 risk 16 increased 17 risk 17 risk 18 for 18 for 20 hf 19 incident 20 hf however , addition of tnf [-] r1 to the previously validated health abc hf risk model did not demonstrate material improvement in net discrimination or reclassification . 0 ###LEFT-WALL### 3 addition 0 ###LEFT-WALL### 19 demonstrate 0 ###LEFT-WALL### 27 . 1 however 2 , 1 however 3 addition 3 addition 4 of 3 addition 17 did 4 of 7 r1 5 tnf 7 r1 7 r1 8 to 8 to 16 model 9 the 16 model 10 previously 11 validated 11 validated 16 model 12 health 13 abc 13 abc 14 hf 14 hf 16 model 15 risk 16 model 17 did 18 not 17 did 19 demonstrate 19 demonstrate 21 improvement 19 demonstrate 22 in 20 material 21 improvement 22 in 25 or 23 net 24 discrimination 24 discrimination 25 or 25 or 26 reclassification the authors first examined the concurrent moderating role of lifestyle engagement on the relation between cognitive status ( [cognitively] elite [,] cognitively normal [[] cn ] , [and] cognitively impaired [ ci ] [ )(and executive functioning ( ef ) in older adults . 0 ###LEFT-WALL### 2 authors 0 ###LEFT-WALL### 4 examined 0 ###LEFT-WALL### 44 . 1 the 2 authors 2 authors 4 examined 3 first 4 examined 4 examined 35 )(and 4 examined 41 in 5 the 8 role 6 concurrent 8 role 7 moderating 8 role 8 role 9 of 8 role 12 on 8 role 35 )(and 9 of 11 engagement 10 lifestyle 11 engagement 12 on 14 relation 13 the 14 relation 14 relation 15 between 15 between 17 status 16 cognitive 17 status 17 status 25 cn 17 status 30 impaired 17 status 32 ci 18 ( 25 cn 20 elite 25 cn 22 cognitively 23 normal 23 normal 25 cn 25 cn 26 ] 27 , 30 impaired 29 cognitively 30 impaired 31 [ 32 ci 32 ci 33 ] 35 )(and 36 executive 35 )(and 37 functioning 35 )(and 39 ef 38 ( 39 ef 39 ef 40 ) 41 in 43 adults 42 older 43 adults second , the authors examined whether baseline participation in lifestyle activities predicted differential 4.5 - year stabilities and transitions in cognitive status . 0 ###LEFT-WALL### 4 authors 0 ###LEFT-WALL### 5 examined 0 ###LEFT-WALL### 15 - 1 second 2 , 1 second 4 authors 3 the 4 authors 4 authors 5 examined 5 examined 6 whether 6 whether 8 participation 6 whether 12 predicted 7 baseline 8 participation 8 participation 9 in 8 participation 12 predicted 9 in 11 activities 10 lifestyle 11 activities 12 predicted 13 differential 13 differential 14 4.5 15 - 18 and 15 - 23 . 16 year 17 stabilities 17 stabilities 18 and 18 and 19 transitions 18 and 20 in 20 in 22 status 21 cognitive 22 status participants ( initial n = 501 [;] 53 - 90 years ) were from the victoria longitudinal study . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 13 were 0 ###LEFT-WALL### 19 . 1 participants 11 years 1 participants 13 were 2 ( 11 years 3 initial 5 = 3 initial 11 years 4 n 5 = 5 = 6 501 8 53 9 - 9 - 10 90 9 - 11 years 11 years 12 ) 13 were 14 from 14 from 18 study 15 the 18 study 16 victoria 17 longitudinal 17 longitudinal 18 study ef was represented by [a] 1 - factor structure . 0 ###LEFT-WALL### 1 ef 0 ###LEFT-WALL### 3 represented 0 ###LEFT-WALL### 7 - 1 ef 2 was 2 was 3 represented 3 represented 4 by 4 by 6 1 7 - 8 factor 7 - 10 . 8 factor 9 structure lifestyle activities were measured in multiple domains of engagement ( e.g [.] , cognitive , physical , and social ) . 0 ###LEFT-WALL### 2 activities 0 ###LEFT-WALL### 4 measured 0 ###LEFT-WALL### 15 , 0 ###LEFT-WALL### 21 . 1 lifestyle 2 activities 2 activities 3 were 3 were 4 measured 4 measured 5 in 4 measured 13 , 4 measured 14 cognitive 5 in 7 domains 6 multiple 7 domains 7 domains 8 of 8 of 9 engagement 9 engagement 11 e.g 10 ( 11 e.g 11 e.g 13 , 15 , 18 and 16 physical 18 and 17 , 18 and 18 and 19 social 18 and 20 ) two - wave status stability groups included sustained normal aging , transitional early impairment , and chronic impairment . 0 ###LEFT-WALL### 1 two 0 ###LEFT-WALL### 2 - 0 ###LEFT-WALL### 19 . 2 - 16 and 3 wave 6 groups 4 status 6 groups 5 stability 6 groups 6 groups 7 included 6 groups 8 sustained 6 groups 10 aging 6 groups 11 , 8 sustained 9 normal 11 , 14 impairment 11 , 16 and 12 transitional 14 impairment 13 early 14 impairment 15 , 16 and 16 and 18 impairment 17 chronic 18 impairment hierarchical regressions showed that baseline participation in social activities moderated cognitive status differences in ef . 0 ###LEFT-WALL### 2 regressions 0 ###LEFT-WALL### 3 showed 0 ###LEFT-WALL### 16 . 1 hierarchical 2 regressions 2 regressions 3 showed 3 showed 4 that 4 that 6 participation 4 that 10 moderated 5 baseline 6 participation 6 participation 7 in 6 participation 10 moderated 7 in 9 activities 8 social 9 activities 10 moderated 13 differences 10 moderated 14 in 11 cognitive 12 status 12 status 13 differences 14 in 15 ef ci adults with high ( but not low [ )(social engagement performed equivalently to cn adults on ef . 0 ###LEFT-WALL### 2 adults 0 ###LEFT-WALL### 12 performed 0 ###LEFT-WALL### 19 . 1 ci 2 adults 2 adults 3 with 2 adults 12 performed 3 with 11 engagement 4 high 6 but 5 ( 6 but 6 but 7 not 6 but 8 low 6 but 11 engagement 7 not 8 low 10 )(social 11 engagement 12 performed 13 equivalently 12 performed 14 to 12 performed 17 on 14 to 16 adults 15 cn 16 adults 17 on 18 ef longitudinally , logistic regressions showed that engagement in physical activities was a significant predictor of stability of cognitive status . 0 ###LEFT-WALL### 4 regressions 0 ###LEFT-WALL### 5 showed 0 ###LEFT-WALL### 20 . 1 longitudinally 2 , 1 longitudinally 4 regressions 3 logistic 4 regressions 4 regressions 5 showed 5 showed 6 that 6 that 7 engagement 6 that 11 was 7 engagement 8 in 7 engagement 11 was 8 in 10 activities 9 physical 10 activities 11 was 14 predictor 12 a 13 significant 12 a 14 predictor 13 significant 14 predictor 14 predictor 15 of 15 of 16 stability 16 stability 17 of 17 of 19 status 18 cognitive 19 status ci adults who were more engaged in physical activities were more likely to improve in their cognitive status over time than their more sedentary peers . 0 ###LEFT-WALL### 2 adults 0 ###LEFT-WALL### 10 were 0 ###LEFT-WALL### 26 . 1 ci 2 adults 2 adults 3 who 2 adults 4 were 2 adults 10 were 3 who 4 were 4 were 5 more 4 were 6 engaged 6 engaged 7 in 7 in 9 activities 8 physical 9 activities 10 were 12 likely 11 more 12 likely 12 likely 13 to 12 likely 14 improve 13 to 14 improve 14 improve 15 in 14 improve 19 over 14 improve 21 than 15 in 18 status 16 their 18 status 17 cognitive 18 status 19 over 20 time 21 than 25 peers 22 their 25 peers 23 more 24 sedentary 24 sedentary 25 peers participation in cognitive activities was a significant predictor of maintenance in a higher cognitive status group . 0 ###LEFT-WALL### 1 participation 0 ###LEFT-WALL### 5 was 0 ###LEFT-WALL### 17 . 1 participation 2 in 1 participation 5 was 2 in 4 activities 3 cognitive 4 activities 5 was 8 predictor 6 a 7 significant 6 a 8 predictor 7 significant 8 predictor 8 predictor 9 of 9 of 10 maintenance 10 maintenance 11 in 11 in 16 group 12 a 16 group 13 higher 15 status 14 cognitive 15 status 15 status 16 group given that lifestyle engagement plays a detectable role in healthy , normal , and impaired neuropsychological aging , further research in activity - related associations and interventions is recommended . 0 ###LEFT-WALL### 20 research 0 ###LEFT-WALL### 29 recommended 0 ###LEFT-WALL### 30 . 1 given 3 lifestyle 1 given 14 and 1 given 18 , 1 given 20 research 2 that 3 lifestyle 3 lifestyle 4 engagement 3 lifestyle 9 in 4 engagement 5 plays 5 plays 8 role 5 plays 9 in 6 a 7 detectable 6 a 8 role 7 detectable 8 role 10 healthy 11 , 11 , 12 normal 11 , 14 and 13 , 14 and 14 and 17 aging 15 impaired 17 aging 16 neuropsychological 17 aging 19 further 20 research 20 research 21 in 20 research 28 is 21 in 22 activity 23 - 24 related 24 related 26 and 24 related 28 is 25 associations 26 and 26 and 27 interventions 28 is 29 recommended mutant n - terminal huntingtin ( htt ) protein resulting from huntington 's disease ( hd ) with expanded polyglutamine accumulates and forms aggregates in vulnerable neurons . 0 ###LEFT-WALL### 9 protein 0 ###LEFT-WALL### 24 aggregates 0 ###LEFT-WALL### 28 . 1 mutant 2 n 1 mutant 5 huntingtin 1 mutant 9 protein 3 - 5 huntingtin 4 terminal 5 huntingtin 5 huntingtin 7 htt 5 huntingtin 8 ) 6 ( 7 htt 7 htt 8 ) 9 protein 10 resulting 9 protein 24 aggregates 10 resulting 11 from 10 resulting 18 with 11 from 14 disease 12 huntington 13 's 13 's 14 disease 14 disease 16 hd 15 ( 16 hd 16 hd 17 ) 18 with 20 polyglutamine 19 expanded 20 polyglutamine 20 polyglutamine 22 and 21 accumulates 22 and 22 and 23 forms 24 aggregates 25 in 25 in 27 neurons 26 vulnerable 27 neurons both ubiquitin proteasomal and autophagic pathways contribute to the degradation of mutant htt . 0 ###LEFT-WALL### 6 pathways 0 ###LEFT-WALL### 7 contribute 0 ###LEFT-WALL### 14 . 1 both 6 pathways 2 ubiquitin 6 pathways 3 proteasomal 4 and 4 and 5 autophagic 4 and 6 pathways 6 pathways 7 contribute 7 contribute 8 to 8 to 10 degradation 9 the 10 degradation 10 degradation 11 of 11 of 13 htt 12 mutant 13 htt here , we focus on the involvement [of] [chaperone] - mediated autophagy ( cma ) , a selective form of autophagy in the clearance of htt . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 focus 0 ###LEFT-WALL### 27 . 1 here 2 , 1 here 3 we 3 we 4 focus 4 focus 5 on 4 focus 19 form 4 focus 22 in 5 on 7 involvement 6 the 7 involvement 7 involvement 12 autophagy 10 - 12 autophagy 11 mediated 12 autophagy 12 autophagy 14 cma 12 autophagy 16 , 13 ( 14 cma 14 cma 15 ) 17 a 18 selective 17 a 19 form 18 selective 19 form 19 form 20 of 20 of 21 autophagy 22 in 24 clearance 23 the 24 clearance 24 clearance 25 of 25 of 26 htt selective catabolism in cma is conferred by the presence of a kferq - like targeting motif in the substrates , [by] which [molecular] [chaperones] recognize the hydrophobic surfaces of the misfolded substrates , and transfer them to the lysosomal membrane protein type - 2 a , lamp - 2 a . 0 ###LEFT-WALL### 2 catabolism 0 ###LEFT-WALL### 6 conferred 1 selective 2 catabolism 2 catabolism 3 in 2 catabolism 5 is 3 in 4 cma 5 is 6 conferred 6 conferred 7 by 7 by 9 presence 8 the 9 presence 9 presence 10 of 10 of 12 kferq 11 a 12 kferq 12 kferq 14 like 12 kferq 22 which 13 - 14 like 14 like 15 targeting 14 like 20 , 15 targeting 16 motif 15 targeting 17 in 17 in 19 substrates 18 the 19 substrates 20 , 22 which 22 which 34 and 25 recognize 28 surfaces 25 recognize 34 and 26 the 28 surfaces 27 hydrophobic 28 surfaces 28 surfaces 29 of 29 of 32 substrates 30 the 32 substrates 31 misfolded 32 substrates 33 , 34 and 34 and 35 transfer 34 and 37 to 35 transfer 36 them 37 to 42 type 38 the 42 type 39 lysosomal 40 membrane 40 membrane 42 type 41 protein 42 type 42 type 45 a 42 type 48 - 43 - 45 a 44 2 45 a 45 a 46 , 46 , 48 - 47 lamp 48 - 48 - 50 a 48 - 51 . 49 2 50 a the substrates are taken into the lysosomes through lamp - 2 a [and] are rapidly degraded by the lysosomal enzymes . 0 ###LEFT-WALL### 2 substrates 0 ###LEFT-WALL### 4 taken 0 ###LEFT-WALL### 10 - 1 the 2 substrates 2 substrates 3 are 3 are 4 taken 4 taken 5 into 4 taken 8 through 5 into 7 lysosomes 6 the 7 lysosomes 8 through 9 lamp 10 - 12 a 10 - 16 degraded 10 - 21 . 11 2 12 a 12 a 14 are 14 are 15 rapidly 14 are 16 degraded 16 degraded 17 by 17 by 20 enzymes 18 the 20 enzymes 19 lysosomal 20 enzymes taken together , we summarize the recent evidence [to] [elucidate] that htt is also a potential substrate of cma . 0 ###LEFT-WALL### 4 we 0 ###LEFT-WALL### 5 summarize 0 ###LEFT-WALL### 20 . 1 taken 2 together 1 taken 3 , 1 taken 4 we 4 we 5 summarize 5 summarize 8 evidence 6 the 8 evidence 7 recent 8 evidence 8 evidence 11 that 11 that 12 htt 11 that 13 is 12 htt 13 is 13 is 14 also 13 is 17 substrate 15 a 16 potential 15 a 17 substrate 16 potential 17 substrate 17 substrate 18 of 18 of 19 cma we propose that the manipulation of cma could be a therapeutic strategy for hd . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 propose 0 ###LEFT-WALL### 15 . 1 we 2 propose 2 propose 3 that 3 that 5 manipulation 3 that 9 be 4 the 5 manipulation 5 manipulation 6 of 5 manipulation 8 could 6 of 7 cma 8 could 9 be 9 be 12 strategy 10 a 11 therapeutic 10 a 12 strategy 11 therapeutic 12 strategy 12 strategy 13 for 13 for 14 hd the extracts of the brown alga , ascophyllum nodosum , which contains several bioactive compounds , have been shown to impart biotic and abiotic stress tolerance properties when consumed by animals . 0 ###LEFT-WALL### 2 extracts 0 ###LEFT-WALL### 21 impart 0 ###LEFT-WALL### 32 . 1 the 2 extracts 2 extracts 3 of 2 extracts 17 have 3 of 6 alga 4 the 6 alga 5 brown 6 alga 6 alga 9 nodosum 6 alga 11 which 7 , 9 nodosum 8 ascophyllum 9 nodosum 9 nodosum 10 , 10 , 11 which 11 which 12 contains 11 which 16 , 12 contains 15 compounds 13 several 15 compounds 14 bioactive 15 compounds 17 have 18 been 18 been 19 shown 19 shown 20 to 20 to 21 impart 21 impart 27 properties 21 impart 28 when 21 impart 30 by 22 biotic 23 and 23 and 24 abiotic 23 and 25 stress 25 stress 27 properties 26 tolerance 27 properties 28 when 29 consumed 30 by 31 animals however , the physiological , biochemical and molecular mechanism underlying such effects remain elusive . 0 ###LEFT-WALL### 7 and 0 ###LEFT-WALL### 13 remain 0 ###LEFT-WALL### 15 . 1 however 2 , 1 however 7 and 3 the 6 biochemical 4 physiological 5 , 4 physiological 6 biochemical 6 biochemical 7 and 7 and 9 mechanism 7 and 10 underlying 7 and 13 remain 8 molecular 9 mechanism 10 underlying 12 effects 11 such 12 effects 13 remain 14 elusive we investigated the effect of a . nodosum fucose - containing polymer ( fcp ) on tolerance to thermally induced stress using the invertebrate animal model , caenorhabditis elegans . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 investigated 0 ###LEFT-WALL### 7 . 1 we 2 investigated 2 investigated 4 effect 3 the 4 effect 4 effect 5 of 5 of 6 a 7 . 9 fucose 7 . 10 - 8 nodosum 9 fucose 10 - 28 caenorhabditis 10 - 29 elegans 10 - 30 . 11 containing 12 polymer 11 containing 16 on 11 containing 18 to 11 containing 27 , 11 containing 28 caenorhabditis 12 polymer 14 fcp 13 ( 14 fcp 14 fcp 15 ) 16 on 17 tolerance 18 to 21 stress 19 thermally 20 induced 20 induced 21 stress 21 stress 22 using 22 using 26 model 23 the 26 model 24 invertebrate 26 model 25 animal 26 model 28 caenorhabditis 29 elegans fcp at a concentration of 150 μg [ml] ( - 1 ) significantly improved the life span and tolerance against thermally induced stress in c [.] elegans . 0 ###LEFT-WALL### 1 fcp 0 ###LEFT-WALL### 14 improved 0 ###LEFT-WALL### 18 and 0 ###LEFT-WALL### 28 . 1 fcp 2 at 1 fcp 14 improved 2 at 4 concentration 3 a 4 concentration 4 concentration 5 of 4 concentration 11 1 5 of 7 μg 6 150 7 μg 9 ( 11 1 10 - 11 1 11 1 12 ) 13 significantly 14 improved 14 improved 17 span 15 the 17 span 16 life 17 span 18 and 19 tolerance 18 and 27 elegans 19 tolerance 20 against 19 tolerance 27 elegans 20 against 23 stress 21 thermally 22 induced 22 induced 23 stress 23 stress 24 in 24 in 25 c the treatment increased the [c] [.] elegans survival by approximately 24 % , when the animals were under severe thermally induced stress ( [i.e] [.] 35 °c ) and 27 % under mild stress [(] i.e [.] 30 °c [ )(conditions . 0 ###LEFT-WALL### 2 treatment 0 ###LEFT-WALL### 3 increased 0 ###LEFT-WALL### 29 and 0 ###LEFT-WALL### 42 . 1 the 2 treatment 2 treatment 3 increased 3 increased 8 survival 3 increased 9 by 3 increased 14 when 4 the 8 survival 7 elegans 8 survival 9 by 12 % 10 approximately 11 24 11 24 12 % 13 , 14 when 14 when 16 animals 14 when 17 were 14 when 28 ) 15 the 16 animals 16 animals 17 were 17 were 18 under 18 under 22 stress 19 severe 22 stress 20 thermally 21 induced 21 induced 22 stress 22 stress 27 °c 23 ( 27 °c 26 35 27 °c 27 °c 28 ) 29 and 31 % 29 and 36 i.e 30 27 31 % 31 % 32 under 31 % 36 i.e 32 under 34 stress 33 mild 34 stress 36 i.e 41 )(conditions 38 30 39 °c 39 °c 41 )(conditions the fcp induced differential expression of genes and proteins is associated with stress response pathways . 0 ###LEFT-WALL### 5 expression 0 ###LEFT-WALL### 11 associated 0 ###LEFT-WALL### 16 . 1 the 5 expression 2 fcp 3 induced 3 induced 5 expression 4 differential 5 expression 5 expression 6 of 5 expression 10 is 6 of 8 and 7 genes 8 and 8 and 9 proteins 10 is 11 associated 11 associated 12 with 12 with 15 pathways 13 stress 15 pathways 14 response 15 pathways under thermal stress , fcp treatment significantly altered the expression of 65 proteins ( 54 [up] - regulated [&] 11 down - regulated ) . 0 ###LEFT-WALL### 6 treatment 0 ###LEFT-WALL### 8 altered 0 ###LEFT-WALL### 25 . 1 under 3 stress 1 under 6 treatment 2 thermal 3 stress 4 , 5 fcp 5 fcp 6 treatment 6 treatment 8 altered 7 significantly 8 altered 8 altered 10 expression 8 altered 23 regulated 9 the 10 expression 10 expression 11 of 11 of 12 65 12 65 13 proteins 12 65 18 regulated 13 proteins 15 54 13 proteins 18 regulated 14 ( 15 54 15 54 17 - 18 regulated 20 11 18 regulated 21 down 22 - 23 regulated 23 regulated 24 ) putative functional analysis of fcp [-] induced differential proteins signified an association of altered proteins in stress - related molecular and biochemical pathways of the model worm . 0 ###LEFT-WALL### 3 analysis 0 ###LEFT-WALL### 14 altered 0 ###LEFT-WALL### 19 related 0 ###LEFT-WALL### 28 . 1 putative 3 analysis 2 functional 3 analysis 3 analysis 4 of 3 analysis 9 proteins 3 analysis 13 of 3 analysis 14 altered 4 of 5 fcp 5 fcp 7 induced 8 differential 9 proteins 9 proteins 10 signified 10 signified 12 association 11 an 12 association 12 association 13 of 14 altered 15 proteins 14 altered 16 in 16 in 17 stress 18 - 19 related 19 related 23 pathways 20 molecular 21 and 21 and 22 biochemical 21 and 23 pathways 23 pathways 24 of 24 of 27 worm 25 the 27 worm 26 model 27 worm recent advances within the field of proteomics [,] including both upstream and downstream protocols , have fuelled a transition from simple protein identification to functional analysis . 0 ###LEFT-WALL### 1 recent 0 ###LEFT-WALL### 2 advances 0 ###LEFT-WALL### 15 , 0 ###LEFT-WALL### 27 . 1 recent 2 advances 2 advances 3 within 3 within 12 and 4 the 5 field 5 field 6 of 5 field 9 including 5 field 12 and 6 of 7 proteomics 9 including 10 both 9 including 11 upstream 12 and 14 protocols 13 downstream 14 protocols 15 , 16 have 16 have 17 fuelled 17 fuelled 19 transition 17 fuelled 20 from 17 fuelled 24 to 18 a 19 transition 20 from 23 identification 21 simple 22 protein 22 protein 23 identification 24 to 26 analysis 25 functional 26 analysis a battery of proteomics approaches is now being employed for the analysis of protein expression levels , the monitoring of cellular activities [and] for gaining [an] increased understanding into biochemical pathways . 0 ###LEFT-WALL### 2 battery 0 ###LEFT-WALL### 6 is 0 ###LEFT-WALL### 17 , 0 ###LEFT-WALL### 32 . 1 a 2 battery 2 battery 3 of 2 battery 6 is 3 of 5 approaches 4 proteomics 5 approaches 6 is 7 now 6 is 8 being 6 is 10 for 8 being 9 employed 10 for 12 analysis 11 the 12 analysis 12 analysis 13 of 13 of 16 levels 14 protein 16 levels 15 expression 16 levels 17 , 19 monitoring 17 , 27 increased 18 the 19 monitoring 19 monitoring 20 of 19 monitoring 24 for 19 monitoring 27 increased 20 of 22 activities 21 cellular 22 activities 24 for 25 gaining 27 increased 28 understanding 28 understanding 29 into 29 into 31 pathways 30 biochemical 31 pathways combined , these approaches are changing the way we study disease by allowing accurate and targeted [,] large scale protein analysis , which will provide invaluable insight into disease pathogenesis . 0 ###LEFT-WALL### 4 approaches 0 ###LEFT-WALL### 5 are 1 combined 2 , 1 combined 4 approaches 3 these 4 approaches 4 approaches 5 are 5 are 6 changing 6 changing 8 way 6 changing 11 disease 6 changing 12 by 7 the 8 way 8 way 9 we 8 way 10 study 9 we 10 study 12 by 13 allowing 13 allowing 15 and 14 accurate 15 and 15 and 21 analysis 15 and 23 which 16 targeted 19 scale 18 large 19 scale 19 scale 20 protein 20 protein 21 analysis 22 , 23 which 23 which 24 will 23 which 31 . 24 will 25 provide 25 provide 27 insight 26 invaluable 27 insight 27 insight 28 into 28 into 30 pathogenesis 29 disease 30 pathogenesis neurodegenerative disorders , including alzheimer 's disease ( ad ) , parkinson 's disease ( pd ) , huntington 's disease ( hd ) , amyotrophic lateral sclerosis ( als ) , prion disease , and other diseases that affect the neuromuscular system , are a leading cause of disability in the aging population . 0 ###LEFT-WALL### 2 disorders 0 ###LEFT-WALL### 45 are 0 ###LEFT-WALL### 55 . 1 neurodegenerative 2 disorders 2 disorders 4 including 2 disorders 45 are 3 , 4 including 4 including 7 disease 4 including 44 , 5 alzheimer 6 's 6 's 7 disease 7 disease 9 ad 7 disease 14 disease 7 disease 21 disease 8 ( 9 ad 9 ad 10 ) 11 , 14 disease 12 parkinson 13 's 13 's 14 disease 14 disease 16 pd 14 disease 17 ) 15 ( 16 pd 16 pd 17 ) 18 , 21 disease 19 huntington 20 's 20 's 21 disease 21 disease 23 hd 21 disease 28 sclerosis 21 disease 44 , 22 ( 23 hd 23 hd 24 ) 25 , 28 sclerosis 26 amyotrophic 28 sclerosis 27 lateral 28 sclerosis 28 sclerosis 30 als 28 sclerosis 36 and 28 sclerosis 44 , 29 ( 30 als 30 als 31 ) 32 , 36 and 33 prion 34 disease 34 disease 36 and 35 , 36 and 36 and 38 diseases 36 and 39 that 36 and 40 affect 36 and 44 , 37 other 38 diseases 39 that 40 affect 40 affect 43 system 41 the 43 system 42 neuromuscular 43 system 45 are 48 cause 45 are 51 in 46 a 48 cause 47 leading 48 cause 48 cause 49 of 49 of 50 disability 51 in 54 population 52 the 54 population 53 aging 54 population there are no effective intervention strategies for these disorders and diagnosis is challenging as it relies primarily on clinical symptomatic features , which often overlap at early stages of disease . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 are 1 there 2 are 2 are 6 strategies 3 no 6 strategies 4 effective 6 strategies 5 intervention 6 strategies 6 strategies 7 for 7 for 21 features 8 these 21 features 9 disorders 10 and 10 and 11 diagnosis 10 and 12 is 10 and 18 on 10 and 21 features 12 is 13 challenging 12 is 14 as 14 as 15 it 14 as 16 relies 15 it 16 relies 16 relies 17 primarily 17 primarily 18 on 19 clinical 21 features 20 symptomatic 21 features 21 features 23 which 22 , 23 which 23 which 25 overlap 23 which 31 . 24 often 25 overlap 25 overlap 26 at 26 at 28 stages 27 early 28 stages 28 stages 29 of 29 of 30 disease there is , therefore , an urgent need to develop reliable biomarkers to improve early and specific diagnosis , to track disease progression , to measure molecular responses towards treatment regimes and ultimately devise new therapeutic strategies . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 19 , 0 ###LEFT-WALL### 38 . 1 there 2 is 2 is 4 therefore 2 is 8 need 2 is 13 to 3 , 4 therefore 4 therefore 5 , 6 an 8 need 7 urgent 8 need 8 need 9 to 8 need 10 develop 9 to 10 develop 10 develop 12 biomarkers 11 reliable 12 biomarkers 13 to 14 improve 14 improve 16 and 15 early 16 and 16 and 18 diagnosis 17 specific 18 diagnosis 19 , 20 to 19 , 21 track 19 , 24 , 20 to 21 track 21 track 23 progression 22 disease 23 progression 24 , 25 to 24 , 32 and 25 to 32 and 26 measure 28 responses 26 measure 29 towards 26 measure 32 and 27 molecular 28 responses 29 towards 31 regimes 30 treatment 31 regimes 32 and 34 devise 32 and 37 strategies 33 ultimately 34 devise 35 new 37 strategies 36 therapeutic 37 strategies to accomplish this , a better understanding of disease mechanisms is needed . 0 ###LEFT-WALL### 1 to 0 ###LEFT-WALL### 2 accomplish 0 ###LEFT-WALL### 4 , 0 ###LEFT-WALL### 13 . 1 to 2 accomplish 2 accomplish 3 this 4 , 7 understanding 4 , 12 needed 5 a 7 understanding 6 better 7 understanding 7 understanding 8 of 7 understanding 11 is 8 of 10 mechanisms 9 disease 10 mechanisms 11 is 12 needed in this review we summarize recent advances in the field of proteomics applicable to neurodegenerative disorders , and how these advances are fueling our understanding , diagnosis , and treatment of these complex disorders . 0 ###LEFT-WALL### 21 advances 0 ###LEFT-WALL### 22 are 0 ###LEFT-WALL### 35 . 1 in 3 review 1 in 21 advances 2 this 3 review 3 review 4 we 3 review 5 summarize 3 review 13 applicable 4 we 5 summarize 5 summarize 7 advances 5 summarize 8 in 6 recent 7 advances 8 in 10 field 9 the 10 field 10 field 11 of 11 of 12 proteomics 13 applicable 14 to 14 to 18 and 15 neurodegenerative 16 disorders 16 disorders 18 and 17 , 18 and 18 and 19 how 20 these 21 advances 21 advances 22 are 22 are 23 fueling 23 fueling 29 and 24 our 27 diagnosis 25 understanding 26 , 25 understanding 27 diagnosis 27 diagnosis 29 and 28 , 29 and 29 and 30 treatment 29 and 31 of 31 of 34 disorders 32 these 34 disorders 33 complex 34 disorders in a scenario of increasing life expectancy worldwide , it is mandatory to identify the characteristics of a healthy aging phenotype , including survival predictors , and to disentangle those related to environment/lifestyle versus those related to familiarity/genetics . 0 ###LEFT-WALL### 10 it 0 ###LEFT-WALL### 31 related 1 in 3 scenario 1 in 9 , 1 in 10 it 2 a 3 scenario 3 scenario 4 of 4 of 5 increasing 5 increasing 7 expectancy 5 increasing 8 worldwide 6 life 7 expectancy 10 it 11 is 11 is 12 mandatory 12 mandatory 13 to 12 mandatory 27 and 13 to 27 and 14 identify 16 characteristics 14 identify 23 including 14 identify 27 and 15 the 16 characteristics 16 characteristics 17 of 17 of 21 phenotype 18 a 19 healthy 18 a 21 phenotype 19 healthy 21 phenotype 20 aging 21 phenotype 22 , 23 including 23 including 25 predictors 23 including 26 , 24 survival 25 predictors 26 , 27 and 27 and 28 to 27 and 29 disentangle 28 to 29 disentangle 30 those 31 related 31 related 32 to 31 related 37 to 31 related 39 . 32 to 33 environment/lifestyle 33 environment/lifestyle 34 versus 34 versus 35 those 35 those 36 related 37 to 38 familiarity/genetics to this aim we comprehensively characterised a cohort of 1,160 italian subjects of 90 years and [over] [(] 90+ , mean age 93 years [;] age range 90 - 106 years ) followed for 6 years survival , belonging to 552 sib - ships ( familiar longevity ) recruited ( 2005 - 2008 ) within the eu - funded geha project in three italian geographic areas ( northern , central and southern italy ) different for urban/rural and socio - economical characteristics . 1 to 3 aim 1 to 4 we 2 this 3 aim 4 we 6 characterised 5 comprehensively 6 characterised 6 characterised 8 cohort 7 a 8 cohort 8 cohort 9 of 8 cohort 13 of 9 of 10 1,160 10 1,160 11 italian 10 1,160 12 subjects 11 italian 12 subjects 13 of 16 and 14 90 15 years 15 years 16 and 16 and 24 years 19 90+ 20 , 19 90+ 22 age 21 mean 22 age 22 age 24 years 23 93 24 years 24 years 27 range 24 years 33 followed 24 years 34 for 26 age 27 range 27 range 28 90 27 range 31 years 27 range 33 followed 29 - 31 years 30 106 31 years 31 years 32 ) 34 for 40 to 35 6 36 years 35 6 40 to 36 years 37 survival 37 survival 39 belonging 38 , 39 belonging 40 to 41 552 40 to 42 sib 40 to 49 recruited 42 sib 44 ships 42 sib 49 recruited 43 - 44 ships 44 ships 47 longevity 44 ships 48 ) 45 ( 47 longevity 46 familiar 47 longevity 47 longevity 48 ) 49 recruited 52 - 49 recruited 55 within 50 ( 52 - 51 2005 52 - 52 - 53 2008 52 - 54 ) 55 within 61 project 56 the 61 project 57 eu 59 funded 57 eu 61 project 58 - 59 funded 60 geha 61 project 61 project 62 in 61 project 71 and 62 in 66 areas 63 three 64 italian 64 italian 66 areas 65 geographic 66 areas 67 ( 71 and 68 northern 69 , 69 , 70 central 69 , 71 and 71 and 73 italy 71 and 74 ) 71 and 75 different 71 and 83 . 72 southern 73 italy 75 different 76 for 76 for 78 and 77 urban/rural 78 and 78 and 79 socio 78 and 80 - 78 and 82 characteristics 80 - 82 characteristics 81 economical 82 characteristics 82 characteristics 83 . these parameters , excluding bmi values , were also significantly associated within sib - ships , suggesting a strong familial/genetic component . 0 ###LEFT-WALL### 2 parameters 0 ###LEFT-WALL### 11 associated 1 these 2 parameters 2 parameters 4 excluding 2 parameters 8 were 3 , 4 excluding 4 excluding 6 values 4 excluding 7 , 5 bmi 6 values 8 were 9 also 8 were 11 associated 10 significantly 11 associated 11 associated 12 within 12 within 15 ships 13 sib 14 - 13 sib 15 ships 15 ships 17 suggesting 16 , 17 suggesting 17 suggesting 21 component 17 suggesting 22 . 18 a 19 strong 18 a 21 component 19 strong 21 component 20 familial/genetic 21 component geographical micro - heterogeneity of survival predictors emerged , such as functional and physical status being more important in southern than in central and northern italy . 0 ###LEFT-WALL### 4 heterogeneity 0 ###LEFT-WALL### 8 emerged 1 geographical 4 heterogeneity 2 micro 3 - 2 micro 4 heterogeneity 4 heterogeneity 5 of 4 heterogeneity 8 emerged 5 of 7 predictors 6 survival 7 predictors 8 emerged 11 as 9 , 11 as 10 such 11 as 11 as 15 status 11 as 27 . 12 functional 13 and 13 and 14 physical 13 and 15 status 15 status 16 being 16 being 18 important 17 more 18 important 18 important 19 in 18 important 21 than 19 in 20 southern 21 than 22 in 22 in 26 italy 23 central 24 and 24 and 25 northern 25 northern 26 italy in conclusion , we identified modifiable survival predictors related to specific domains , whose role and importance vary according to the geographic area considered and which can help in interpreting the genetic results obtained by the geha project , whose major aim is the comprehensive evaluation of phenotypic and genetic data . 0 ###LEFT-WALL### 2 conclusion 0 ###LEFT-WALL### 3 , 0 ###LEFT-WALL### 34 obtained 1 in 2 conclusion 3 , 4 we 3 , 5 identified 3 , 13 , 4 we 5 identified 5 identified 8 predictors 5 identified 10 to 6 modifiable 8 predictors 7 survival 8 predictors 8 predictors 9 related 10 to 12 domains 11 specific 12 domains 13 , 14 whose 13 , 18 vary 13 , 25 and 14 whose 15 role 15 role 16 and 16 and 17 importance 16 and 18 vary 18 vary 20 to 19 according 20 to 20 to 23 area 21 the 23 area 22 geographic 23 area 23 area 24 considered 25 and 26 which 25 and 28 help 26 which 27 can 27 can 28 help 28 help 29 in 29 in 30 interpreting 30 interpreting 33 results 30 interpreting 34 obtained 31 the 33 results 32 genetic 33 results 33 results 34 obtained 34 obtained 35 by 35 by 38 project 36 the 38 project 37 geha 38 project 38 project 40 whose 39 , 40 whose 40 whose 42 aim 40 whose 52 . 41 major 42 aim 42 aim 43 is 43 is 46 evaluation 44 the 46 evaluation 45 comprehensive 46 evaluation 46 evaluation 47 of 47 of 51 data 48 phenotypic 49 and 49 and 50 genetic 49 and 51 data stroke is a leading cause of death and the most common cause of long - term disability in the usa . 0 ###LEFT-WALL### 1 stroke 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 21 . 1 stroke 2 is 2 is 5 cause 3 a 5 cause 4 leading 5 cause 5 cause 6 of 5 cause 13 of 6 of 8 and 7 death 8 and 8 and 12 cause 9 the 12 cause 10 most 11 common 11 common 12 cause 13 of 17 disability 14 long 15 - 14 long 16 term 16 term 17 disability 17 disability 18 in 18 in 20 usa 19 the 20 usa women have a lower incidence [of] stroke compared with men throughout most of the lifespan which has been ascribed to protective effects of gonadal steroids , [most] notably estrogen . 0 ###LEFT-WALL### 1 women 0 ###LEFT-WALL### 2 have 0 ###LEFT-WALL### 30 . 1 women 2 have 2 have 7 stroke 2 have 12 most 3 a 7 stroke 4 lower 5 incidence 5 incidence 7 stroke 7 stroke 8 compared 8 compared 9 with 8 compared 11 throughout 9 with 10 men 12 most 13 of 13 of 15 lifespan 14 the 15 lifespan 15 lifespan 16 which 15 lifespan 17 has 16 which 17 has 17 has 18 been 18 been 19 ascribed 19 ascribed 20 to 19 ascribed 26 , 19 ascribed 29 estrogen 20 to 22 effects 21 protective 22 effects 22 effects 23 of 23 of 25 steroids 24 gonadal 25 steroids 28 notably 29 estrogen due to the lower stroke incidence observed in pre - menopausal women and robust preclinical evidence of neuroprotective and anti - inflammatory properties of estrogen , researchers have focused on the potential benefits of hormones to reduce ischemic brain injury . 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 29 focused 0 ###LEFT-WALL### 41 . 1 due 2 to 1 due 7 observed 1 due 8 in 1 due 13 and 2 to 6 incidence 3 the 6 incidence 4 lower 5 stroke 5 stroke 6 incidence 8 in 12 women 9 pre 10 - 9 pre 12 women 11 menopausal 12 women 13 and 16 evidence 13 and 17 of 13 and 29 focused 14 robust 16 evidence 15 preclinical 16 evidence 17 of 19 and 18 neuroprotective 19 and 19 and 23 properties 19 and 26 , 19 and 27 researchers 19 and 28 have 20 anti 21 - 20 anti 23 properties 22 inflammatory 23 properties 23 properties 24 of 24 of 25 estrogen 27 researchers 28 have 29 focused 30 on 29 focused 36 to 30 on 33 benefits 31 the 33 benefits 32 potential 33 benefits 33 benefits 34 of 34 of 35 hormones 36 to 37 reduce 37 reduce 40 injury 38 ischemic 39 brain 39 brain 40 injury however , as women age , they are disproportionately affected [by] [stroke] , coincident with the loss of estrogen [with] [menopause] . 0 ###LEFT-WALL### 7 they 0 ###LEFT-WALL### 10 affected 0 ###LEFT-WALL### 22 . 1 however 2 , 1 however 7 they 2 , 3 as 3 as 4 women 3 as 5 age 3 as 6 , 3 as 7 they 4 women 5 age 7 they 8 are 8 are 9 disproportionately 8 are 10 affected 10 affected 13 , 10 affected 14 coincident 14 coincident 15 with 15 with 17 loss 16 the 17 loss 17 loss 18 of 18 of 19 estrogen the risk of [stroke] in elderly women exceeds that of men and it is clear that in some settings estrogen can have pro [-] inflammatory effects . 0 ###LEFT-WALL### 2 risk 0 ###LEFT-WALL### 8 exceeds 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 27 . 1 the 2 risk 2 risk 3 of 2 risk 8 exceeds 3 of 5 in 5 in 7 women 6 elderly 7 women 8 exceeds 9 that 9 that 10 of 10 of 11 men 12 and 13 it 12 and 14 is 13 it 14 is 14 is 15 clear 15 clear 16 that 16 that 20 estrogen 16 that 22 have 17 in 19 settings 17 in 20 estrogen 18 some 19 settings 20 estrogen 21 can 21 can 22 have 22 have 26 effects 23 pro 26 effects 25 inflammatory 26 effects this review will focus on estrogen and inflammation and its interaction with aging . 0 ###LEFT-WALL### 2 review 0 ###LEFT-WALL### 4 focus 0 ###LEFT-WALL### 14 . 1 this 2 review 2 review 3 will 3 will 4 focus 4 focus 5 on 4 focus 12 with 5 on 9 and 6 estrogen 7 and 7 and 8 inflammation 7 and 9 and 9 and 11 interaction 10 its 11 interaction 12 with 13 aging there is ample empirical evidence that cultivation of mindfulness in dedicated target populations has positive health effects , specifically in the context of stress management and mental disorders . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 is 1 there 2 is 2 is 5 evidence 3 ample 5 evidence 4 empirical 5 evidence 5 evidence 6 that 5 evidence 20 in 6 that 7 cultivation 6 that 14 has 7 cultivation 8 of 7 cultivation 10 in 7 cultivation 14 has 8 of 9 mindfulness 10 in 13 populations 11 dedicated 12 target 12 target 13 populations 14 has 17 effects 15 positive 16 health 16 health 17 effects 18 , 19 specifically 18 , 20 in 20 in 26 and 20 in 29 . 21 the 22 context 22 context 23 of 22 context 26 and 23 of 25 management 24 stress 25 management 26 and 28 disorders 27 mental 28 disorders research into the effectiveness of mindfulness - based interventions ( mbi ) in age - related conditions and disorders is still in its infancy . 0 ###LEFT-WALL### 1 research 0 ###LEFT-WALL### 20 is 0 ###LEFT-WALL### 25 . 1 research 2 into 1 research 20 is 2 into 4 effectiveness 3 the 4 effectiveness 4 effectiveness 5 of 4 effectiveness 13 in 5 of 9 interventions 6 mindfulness 7 - 6 mindfulness 9 interventions 8 based 9 interventions 9 interventions 11 mbi 10 ( 11 mbi 11 mbi 12 ) 13 in 14 age 15 - 16 related 16 related 18 and 16 related 20 is 17 conditions 18 and 18 and 19 disorders 20 is 21 still 21 still 22 in 22 in 24 infancy 23 its 24 infancy this paper [describes] , [in] brief , the scientific background of mbi and its potential to contribute to successful ageing and the care for and wellbeing of older people . 0 ###LEFT-WALL### 25 and 0 ###LEFT-WALL### 30 . 1 this 2 paper 2 paper 4 , 4 , 6 brief 4 , 7 , 7 , 10 background 7 , 13 and 8 the 10 background 9 scientific 10 background 10 background 11 of 11 of 12 mbi 13 and 15 potential 13 and 16 to 13 and 24 for 13 and 25 and 14 its 15 potential 16 to 17 contribute 17 contribute 18 to 17 contribute 24 for 18 to 21 and 19 successful 20 ageing 20 ageing 21 and 21 and 23 care 22 the 23 care 25 and 26 wellbeing 25 and 27 of 27 of 29 people 28 older 29 people special focus is dedicated to the contribution of optimal cognitive abilities to this success and to what extent mbi may support cognitive reserve . 0 ###LEFT-WALL### 2 focus 0 ###LEFT-WALL### 4 dedicated 0 ###LEFT-WALL### 24 . 1 special 2 focus 2 focus 3 is 3 is 4 dedicated 4 dedicated 5 to 5 to 7 contribution 6 the 7 contribution 7 contribution 8 of 8 of 11 abilities 8 of 19 mbi 8 of 21 support 9 optimal 11 abilities 10 cognitive 11 abilities 11 abilities 15 and 12 to 14 success 12 to 15 and 13 this 14 success 15 and 16 to 16 to 17 what 18 extent 19 mbi 19 mbi 20 may 20 may 21 support 21 support 23 reserve 22 cognitive 23 reserve introduction : although epidemiology studies consistently report increased prevalence of overactive bladder [(] oab ) with age , an accurate deciphering of causative links between the two entities remains elusive . 0 ###LEFT-WALL### 1 introduction 0 ###LEFT-WALL### 2 : 2 : 21 deciphering 2 : 29 remains 2 : 31 . 3 although 5 studies 3 although 7 report 3 although 15 ) 3 although 21 deciphering 4 epidemiology 5 studies 5 studies 7 report 6 consistently 7 report 7 report 9 prevalence 8 increased 9 prevalence 9 prevalence 10 of 10 of 14 oab 11 overactive 14 oab 12 bladder 14 oab 16 with 17 age 16 with 18 , 16 with 21 deciphering 19 an 20 accurate 19 an 21 deciphering 20 accurate 21 deciphering 21 deciphering 22 of 21 deciphering 29 remains 22 of 24 links 23 causative 24 links 24 links 25 between 25 between 28 entities 26 the 27 two 27 two 28 entities 29 remains 30 elusive studies on aged rodent bladder [have] so far yielded contradictory results on age - associated changes in muscarinic receptors , which highlight the challenge posed by species differences in understanding oab pathology . 0 ###LEFT-WALL### 1 studies 0 ###LEFT-WALL### 25 posed 0 ###LEFT-WALL### 33 . 1 studies 2 on 1 studies 25 posed 2 on 11 results 3 aged 4 rodent 4 rodent 11 results 5 bladder 11 results 7 so 8 far 8 far 11 results 9 yielded 11 results 10 contradictory 11 results 11 results 12 on 11 results 21 which 11 results 22 highlight 12 on 13 age 13 age 16 changes 14 - 16 changes 15 associated 16 changes 16 changes 17 in 16 changes 20 , 17 in 19 receptors 18 muscarinic 19 receptors 21 which 22 highlight 22 highlight 24 challenge 23 the 24 challenge 25 posed 26 by 25 posed 29 in 26 by 28 differences 27 species 28 differences 29 in 30 understanding 30 understanding 32 pathology 31 oab 32 pathology we hypothesized that age - related biochemical changes in bladder leading to altered bladder function will be reflected in altered urinary proteome of elderly oab patients . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 hypothesized 0 ###LEFT-WALL### 27 . 1 we 2 hypothesized 2 hypothesized 3 that 3 that 4 age 3 that 18 reflected 4 age 17 be 5 - 6 related 6 related 8 changes 6 related 9 in 6 related 12 to 6 related 17 be 7 biochemical 8 changes 9 in 11 leading 10 bladder 11 leading 12 to 16 will 13 altered 14 bladder 14 bladder 16 will 15 function 16 will 17 be 18 reflected 18 reflected 19 in 19 in 22 proteome 20 altered 22 proteome 21 urinary 22 proteome 22 proteome 23 of 23 of 26 patients 24 elderly 26 patients 25 oab 26 patients methods : single time point urine specimens were obtained from 140 oab patients in the age range of 25 - 90 years of either sex coming routinely to the urology clinics . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 7 specimens 2 : 9 obtained 2 : 32 . 3 single 7 specimens 4 time 7 specimens 5 point 6 urine 6 urine 7 specimens 7 specimens 8 were 8 were 9 obtained 9 obtained 10 from 9 obtained 14 in 10 from 13 patients 11 140 13 patients 12 oab 13 patients 14 in 17 range 15 the 17 range 16 age 17 range 17 range 18 of 18 of 22 years 19 25 20 - 20 - 21 90 20 - 22 years 22 years 23 of 22 years 28 to 23 of 25 sex 24 either 25 sex 25 sex 26 coming 26 coming 27 routinely 28 to 31 clinics 29 the 31 clinics 30 urology 31 clinics eight chemokines in urine were measured by milliplex map human cytokine/chemokine multiplex [immunoassay] and elisa . 0 ###LEFT-WALL### 2 chemokines 0 ###LEFT-WALL### 5 were 0 ###LEFT-WALL### 16 . 1 eight 2 chemokines 2 chemokines 3 in 2 chemokines 5 were 3 in 4 urine 5 were 6 measured 6 measured 7 by 7 by 14 and 8 milliplex 9 map 9 map 12 multiplex 10 human 11 cytokine/chemokine 11 cytokine/chemokine 12 multiplex 12 multiplex 14 and 14 and 15 elisa multivariate and univariate statistical analyses were done to determine association [of] age with urinary chemokines in oab patients . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 6 were 0 ###LEFT-WALL### 19 . 1 multivariate 2 and 2 and 5 analyses 2 and 6 were 3 univariate 5 analyses 4 statistical 5 analyses 6 were 7 done 7 done 8 to 7 done 13 with 8 to 9 determine 9 determine 12 age 10 association 12 age 13 with 15 chemokines 14 urinary 15 chemokines 15 chemokines 16 in 16 in 18 patients 17 oab 18 patients results : in agreement with age - dependent higher prevalence of oab , the logistic regression of the data also revealed the significant association of oab symptoms with age [ odds [ratio] ( or [ )(1.12 [;] 95 % ci , ( 1.072 , 1.187 ) , p = 0.0001 ] . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 13 , 0 ###LEFT-WALL### 52 . 1 results 2 : 2 : 3 in 3 in 4 agreement 4 agreement 5 with 5 with 6 age 6 age 10 prevalence 7 - 10 prevalence 8 dependent 10 prevalence 9 higher 10 prevalence 10 prevalence 11 of 10 prevalence 13 , 11 of 12 oab 13 , 16 regression 13 , 21 revealed 14 the 16 regression 15 logistic 16 regression 16 regression 17 of 16 regression 21 revealed 17 of 19 data 18 the 19 data 20 also 21 revealed 21 revealed 24 association 22 the 24 association 23 significant 24 association 24 association 25 of 24 association 31 odds 25 of 27 symptoms 26 oab 27 symptoms 27 symptoms 28 with 28 with 29 age 30 [ 31 odds 31 odds 40 ci 31 odds 43 1.072 31 odds 51 ] 33 ( 40 ci 34 or 36 )(1.12 34 or 40 ci 38 95 40 ci 39 % 40 ci 40 ci 41 , 42 ( 43 1.072 43 1.072 45 1.187 43 1.072 49 = 43 1.072 51 ] 44 , 45 1.187 45 1.187 46 ) 47 , 49 = 48 p 49 = 49 = 50 0.0001 49 = 51 ] univariate analysis of 8 urinary proteins revealed an age - associated elevation of ngf ( nerve growth [factor] ) in 137 out of 140 oab patients [ pearson r = 0.274 ; 95 %ci ( 0.112 - 0.422 ) [;] p = 0.001 ] . 0 ###LEFT-WALL### 2 analysis 0 ###LEFT-WALL### 7 revealed 0 ###LEFT-WALL### 32 ; 0 ###LEFT-WALL### 45 . 1 univariate 2 analysis 2 analysis 3 of 2 analysis 7 revealed 3 of 6 proteins 4 8 6 proteins 5 urinary 6 proteins 7 revealed 9 age 7 revealed 20 in 8 an 9 age 9 age 12 elevation 10 - 12 elevation 11 associated 12 elevation 12 elevation 13 of 12 elevation 17 growth 12 elevation 19 ) 13 of 14 ngf 15 ( 17 growth 16 nerve 17 growth 17 growth 19 ) 20 in 21 137 21 137 23 of 22 out 23 of 23 of 26 patients 24 140 25 oab 25 oab 26 patients 26 patients 28 pearson 27 [ 28 pearson 28 pearson 30 = 28 pearson 32 ; 29 r 30 = 30 = 31 0.274 30 = 32 ; 32 ; 33 95 32 ; 34 %ci 33 95 34 %ci 34 %ci 42 = 35 ( 37 - 36 0.112 37 - 37 - 38 0.422 37 - 39 ) 37 - 42 = 41 p 42 = 42 = 43 0.001 42 = 44 ] modest correlation with age was also noted for mcp - 1 ( monocyte chemoattractant protein - 1 ) , which was detected in 115 oab patients , and the remaining chemokines were undetectable in nearly two - third [of] oab patients included in our cohort . 0 ###LEFT-WALL### 7 noted 1 modest 2 correlation 1 modest 5 was 1 modest 7 noted 2 correlation 3 with 2 correlation 5 was 3 with 4 age 6 also 7 noted 7 noted 8 for 8 for 9 mcp 9 mcp 11 1 9 mcp 17 1 9 mcp 20 which 10 - 11 1 11 1 15 protein 11 1 16 - 12 ( 15 protein 13 monocyte 14 chemoattractant 14 chemoattractant 15 protein 15 protein 16 - 16 - 17 1 17 1 18 ) 19 , 20 which 20 which 21 was 21 was 22 detected 22 detected 23 in 22 detected 33 undetectable 23 in 25 oab 24 115 25 oab 25 oab 28 and 25 oab 32 were 26 patients 28 and 27 , 28 and 28 and 31 chemokines 28 and 32 were 29 the 30 remaining 29 the 31 chemokines 33 undetectable 34 in 34 in 36 two 35 nearly 36 two 36 two 41 patients 37 - 41 patients 38 third 41 patients 40 oab 41 patients 41 patients 42 included 41 patients 46 . 42 included 43 in 43 in 45 cohort 44 our 45 cohort conclusions : based on our findings , we postulate that age - associated biochemical changes may accentuate the inflammation associated with oab . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 3 based 0 ###LEFT-WALL### 7 , 1 conclusions 2 : 2 : 3 based 3 based 4 on 4 on 6 findings 5 our 6 findings 7 , 8 we 7 , 9 postulate 7 , 12 - 8 we 9 postulate 9 postulate 11 age 10 that 11 age 12 - 15 changes 12 - 17 accentuate 12 - 23 . 13 associated 15 changes 14 biochemical 15 changes 15 changes 16 may 16 may 17 accentuate 17 accentuate 19 inflammation 18 the 19 inflammation 19 inflammation 20 associated 20 associated 21 with 21 with 22 oab urinary ngf elevation in elderly oab patients may be a homeostatic response to counter the senescence of bladder nerves and arrest the progression of oab into detrusor hyperactivity with impaired contractility . 0 ###LEFT-WALL### 3 elevation 0 ###LEFT-WALL### 20 and 0 ###LEFT-WALL### 32 . 1 urinary 2 ngf 2 ngf 3 elevation 3 elevation 4 in 3 elevation 8 may 4 in 7 patients 5 elderly 7 patients 6 oab 7 patients 8 may 9 be 9 be 12 response 9 be 13 to 10 a 11 homeostatic 10 a 12 response 11 homeostatic 12 response 13 to 20 and 14 counter 16 senescence 14 counter 20 and 15 the 16 senescence 16 senescence 17 of 17 of 19 nerves 18 bladder 19 nerves 20 and 21 arrest 21 arrest 23 progression 21 arrest 29 with 22 the 23 progression 23 progression 24 of 24 of 25 oab 25 oab 26 into 26 into 28 hyperactivity 27 detrusor 28 hyperactivity 29 with 31 contractility 30 impaired 31 contractility likewise , elevation of mcp - 1 may be related to decreased muscle mass and increased content of adipose tissue in bladder [of] elderly oab patients . 0 ###LEFT-WALL### 15 and 0 ###LEFT-WALL### 27 . 1 likewise 14 mass 2 , 10 related 3 elevation 4 of 3 elevation 10 related 4 of 5 mcp 5 mcp 7 1 5 mcp 9 be 6 - 7 1 7 1 8 may 8 may 9 be 10 related 11 to 10 related 14 mass 11 to 13 muscle 12 decreased 13 muscle 14 mass 15 and 15 and 16 increased 16 increased 17 content 16 increased 21 in 17 content 18 of 18 of 20 tissue 19 adipose 20 tissue 21 in 26 patients 22 bladder 26 patients 24 elderly 26 patients 25 oab 26 patients urinary ngf and mcp - 1 can serve as surrogate markers for monitoring age - associated biochemical changes and the effect of therapeutic interventions in oab patients . 0 ###LEFT-WALL### 2 ngf 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 28 . 1 urinary 2 ngf 3 and 4 mcp 3 and 16 associated 4 mcp 8 serve 4 mcp 16 associated 5 - 8 serve 6 1 8 serve 7 can 8 serve 8 serve 9 as 8 serve 12 for 8 serve 15 - 9 as 11 markers 10 surrogate 11 markers 12 for 13 monitoring 13 monitoring 14 age 16 associated 19 and 16 associated 25 in 17 biochemical 18 changes 18 changes 19 and 19 and 21 effect 19 and 22 of 20 the 21 effect 22 of 24 interventions 23 therapeutic 24 interventions 25 in 27 patients 26 oab 27 patients as life expectancy increases , it is imperative that health care providers recognize the importance of safe medication use within an aging geriatric population . 0 ###LEFT-WALL### 6 it 0 ###LEFT-WALL### 7 is 0 ###LEFT-WALL### 25 . 1 as 4 increases 1 as 5 , 1 as 6 it 2 life 4 increases 3 expectancy 4 increases 6 it 7 is 7 is 8 imperative 8 imperative 9 that 9 that 12 providers 9 that 13 recognize 10 health 12 providers 11 care 12 providers 12 providers 13 recognize 13 recognize 15 importance 13 recognize 20 within 14 the 15 importance 15 importance 16 of 16 of 19 use 17 safe 19 use 18 medication 19 use 20 within 24 population 21 an 24 population 22 aging 24 population 23 geriatric 24 population dealing with a cohort that has different biological and medical demands requires pharmacists to pay particular attention to details when treating this subset of individuals . 0 ###LEFT-WALL### 1 dealing 0 ###LEFT-WALL### 12 requires 0 ###LEFT-WALL### 26 . 1 dealing 2 with 1 dealing 12 requires 2 with 4 cohort 3 a 4 cohort 4 cohort 5 that 4 cohort 6 has 5 that 6 has 6 has 11 demands 7 different 11 demands 8 biological 9 and 9 and 10 medical 9 and 11 demands 12 requires 13 pharmacists 12 requires 14 to 12 requires 15 pay 14 to 15 pay 15 pay 17 attention 15 pay 18 to 15 pay 20 when 16 particular 17 attention 18 to 19 details 20 when 21 treating 21 treating 23 subset 22 this 23 subset 23 subset 24 of 24 of 25 individuals in particular , this manuscript will focus on alzheimer 's disease ( ad ) and considerations when dealing with new treatment options . 0 ###LEFT-WALL### 2 particular 0 ###LEFT-WALL### 3 , 0 ###LEFT-WALL### 23 . 1 in 2 particular 3 , 15 and 4 this 7 focus 5 manuscript 7 focus 6 will 7 focus 7 focus 8 on 7 focus 15 and 8 on 11 disease 9 alzheimer 10 's 10 's 11 disease 11 disease 13 ad 12 ( 13 ad 13 ad 14 ) 15 and 16 considerations 15 and 17 when 17 when 18 dealing 17 when 22 options 18 dealing 19 with 18 dealing 22 options 19 with 21 treatment 20 new 21 treatment the food and drug administration 's recent approval of the increased dosage strength , donepezil 23 [mg] , previously only available in 5 mg and 10 mg strengths , has raised efficacy and safety concerns . 0 ###LEFT-WALL### 8 approval 0 ###LEFT-WALL### 31 raised 0 ###LEFT-WALL### 36 . 1 the 5 administration 2 food 3 and 3 and 4 drug 4 drug 5 administration 5 administration 6 's 6 's 8 approval 7 recent 8 approval 8 approval 9 of 8 approval 15 donepezil 8 approval 21 available 8 approval 30 has 9 of 13 strength 10 the 13 strength 11 increased 12 dosage 12 dosage 13 strength 14 , 15 donepezil 15 donepezil 16 23 15 donepezil 18 , 18 , 21 available 19 previously 21 available 20 only 21 available 21 available 22 in 21 available 29 , 22 in 28 strengths 23 5 24 mg 24 mg 25 and 25 and 27 mg 25 and 28 strengths 26 10 27 mg 30 has 31 raised 31 raised 33 and 32 efficacy 33 and 33 and 35 concerns 34 safety 35 concerns reservations stem from unproven superiority along with an increased incidence of adverse events . 0 ###LEFT-WALL### 1 reservations 0 ###LEFT-WALL### 2 stem 0 ###LEFT-WALL### 14 . 1 reservations 2 stem 2 stem 3 from 2 stem 7 with 3 from 5 superiority 4 unproven 5 superiority 6 along 7 with 7 with 10 incidence 8 an 10 incidence 9 increased 10 incidence 10 incidence 11 of 11 of 13 events 12 adverse 13 events the purpose of the manuscript is to provide a brief insight into these concerns and provide readers the knowledge necessary to make a clinically sound decision when treating patients with moderate - [to] [-] severe ad . 0 ###LEFT-WALL### 2 purpose 0 ###LEFT-WALL### 22 make 0 ###LEFT-WALL### 37 . 1 the 2 purpose 2 purpose 3 of 2 purpose 6 is 3 of 5 manuscript 4 the 5 manuscript 6 is 7 to 6 is 15 and 7 to 15 and 8 provide 11 insight 8 provide 12 into 8 provide 15 and 9 a 11 insight 10 brief 11 insight 12 into 14 concerns 13 these 14 concerns 15 and 16 provide 15 and 19 knowledge 16 provide 17 readers 18 the 19 knowledge 19 knowledge 20 necessary 20 necessary 21 to 21 to 22 make 22 make 26 decision 22 make 27 when 22 make 30 with 23 a 26 decision 24 clinically 25 sound 25 sound 26 decision 27 when 28 treating 28 treating 29 patients 30 with 36 ad 31 moderate 32 - 31 moderate 36 ad 35 severe 36 ad interacting with older adults is a daily practice for pharmacists . 0 ###LEFT-WALL### 1 interacting 0 ###LEFT-WALL### 5 is 0 ###LEFT-WALL### 11 . 1 interacting 2 with 1 interacting 5 is 2 with 4 adults 3 older 4 adults 5 is 8 practice 6 a 7 daily 6 a 8 practice 7 daily 8 practice 8 practice 9 for 9 for 10 pharmacists it is important to understand how medications affect their wellbeing , but there are many other factors that affect quality of life . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 11 , 0 ###LEFT-WALL### 23 . 1 it 2 is 2 is 3 important 3 important 4 to 3 important 5 understand 4 to 5 understand 5 understand 6 how 6 how 7 medications 6 how 8 affect 7 medications 8 affect 8 affect 10 wellbeing 9 their 10 wellbeing 11 , 12 but 11 , 14 are 12 but 13 there 12 but 14 are 14 are 17 factors 15 many 16 other 16 other 17 factors 17 factors 18 that 17 factors 19 affect 18 that 19 affect 19 affect 20 quality 20 quality 21 of 21 of 22 life to truly understand some of the challenges facing older adults , emily anastasia , a sixth - year pharmacy student at the university of rhode island , moved into south bay retirement living , a senior living community , for an eight [-] day immersion experience as a special project within one of her advanced pharmacy practice experience rotations . 0 ###LEFT-WALL### 1 to 0 ###LEFT-WALL### 11 , 1 to 3 understand 2 truly 3 understand 3 understand 7 challenges 4 some 5 of 4 some 7 challenges 5 of 7 challenges 6 the 7 challenges 7 challenges 8 facing 8 facing 10 adults 9 older 10 adults 11 , 13 anastasia 11 , 14 , 12 emily 13 anastasia 14 , 16 sixth 15 a 16 sixth 16 sixth 20 student 16 sixth 28 moved 17 - 20 student 18 year 20 student 19 pharmacy 20 student 20 student 21 at 20 student 24 of 20 student 27 , 21 at 23 university 22 the 23 university 24 of 26 island 25 rhode 26 island 28 moved 29 into 28 moved 33 living 28 moved 40 for 29 into 30 south 31 bay 32 retirement 32 retirement 33 living 33 living 38 community 34 , 38 community 35 a 36 senior 35 a 38 community 36 senior 38 community 37 living 38 community 38 community 39 , 40 for 46 experience 41 an 46 experience 42 eight 46 experience 44 day 46 experience 45 immersion 46 experience 46 experience 55 advanced 47 as 50 project 47 as 55 advanced 48 a 49 special 48 a 50 project 49 special 50 project 50 project 51 within 50 project 53 of 50 project 55 advanced 51 within 52 one 53 of 54 her 55 advanced 59 rotations 55 advanced 60 . 56 pharmacy 59 rotations 57 practice 58 experience 58 experience 59 rotations during her stay , she did not attend classes nor leave the facility [unless] on the south bay bus with the other assisted living residents . 0 ###LEFT-WALL### 5 she 0 ###LEFT-WALL### 10 nor 0 ###LEFT-WALL### 26 . 1 during 3 stay 1 during 4 , 1 during 5 she 2 her 3 stay 5 she 6 did 6 did 7 not 6 did 10 nor 8 attend 9 classes 8 attend 10 nor 10 nor 11 leave 10 nor 20 with 11 leave 13 facility 11 leave 15 on 12 the 13 facility 15 on 19 bus 16 the 19 bus 17 south 18 bay 18 bay 19 bus 20 with 25 residents 21 the 22 other 22 other 25 residents 23 assisted 24 living 24 living 25 residents she lived with a 92 [-] year - old roommate , developed close friendships with many of the residents , and kept a detailed journal of her experience . 0 ###LEFT-WALL### 1 she 0 ###LEFT-WALL### 21 and 0 ###LEFT-WALL### 29 . 1 she 21 and 2 lived 3 with 2 lived 21 and 3 with 7 year 4 a 7 year 5 92 7 year 7 year 14 friendships 8 - 14 friendships 9 old 14 friendships 10 roommate 11 , 10 roommate 14 friendships 12 developed 14 friendships 13 close 14 friendships 14 friendships 15 with 14 friendships 20 , 15 with 19 residents 16 many 17 of 16 many 19 residents 17 of 19 residents 18 the 19 residents 20 , 21 and 21 and 22 kept 22 kept 25 journal 23 a 24 detailed 23 a 25 journal 24 detailed 25 journal 25 journal 26 of 26 of 28 experience 27 her 28 experience the purpose of this reflection is to share her experience and recognize lifestyle as well as social and physical environment as factors in understanding the aging process . 0 ###LEFT-WALL### 2 purpose 0 ###LEFT-WALL### 28 . 1 the 2 purpose 2 purpose 3 of 2 purpose 6 is 3 of 5 reflection 4 this 5 reflection 6 is 7 to 6 is 11 and 7 to 11 and 8 share 10 experience 8 share 11 and 9 her 10 experience 11 and 12 recognize 12 recognize 13 lifestyle 13 lifestyle 16 as 14 as 15 well 15 well 16 as 16 as 18 and 17 social 18 and 18 and 20 environment 18 and 21 as 19 physical 20 environment 21 as 22 factors 22 factors 23 in 23 in 24 understanding 24 understanding 27 process 25 the 27 process 26 aging 27 process immersing a pharmacy student within an assisted living community provides a unique opportunity to observe and [appreciate] characteristics of older adults that cannot be learned within a classroom setting . 0 ###LEFT-WALL### 1 immersing 0 ###LEFT-WALL### 10 provides 0 ###LEFT-WALL### 16 and 0 ###LEFT-WALL### 30 . 1 immersing 4 student 1 immersing 5 within 1 immersing 10 provides 2 a 4 student 3 pharmacy 4 student 5 within 9 community 6 an 9 community 7 assisted 8 living 8 living 9 community 10 provides 13 opportunity 11 a 13 opportunity 12 unique 13 opportunity 13 opportunity 14 to 13 opportunity 15 observe 14 to 15 observe 16 and 18 characteristics 16 and 24 be 18 characteristics 19 of 18 characteristics 22 that 18 characteristics 23 cannot 18 characteristics 24 be 19 of 21 adults 20 older 21 adults 22 that 23 cannot 24 be 25 learned 25 learned 26 within 26 within 29 setting 27 a 29 setting 28 classroom 29 setting purpose : informal caregivers play a critical role in the care of individuals who are aging or have disabilities [and] [are] at increased risk for poor health outcomes . 0 ###LEFT-WALL### 1 purpose 0 ###LEFT-WALL### 2 : 2 : 4 caregivers 2 : 18 have 2 : 29 . 3 informal 4 caregivers 4 caregivers 17 or 5 play 8 role 5 play 9 in 5 play 17 or 6 a 8 role 7 critical 8 role 9 in 11 care 10 the 11 care 11 care 12 of 12 of 13 individuals 13 individuals 14 who 13 individuals 15 are 14 who 15 are 15 are 16 aging 17 or 18 have 18 have 19 disabilities 18 have 22 at 18 have 25 for 22 at 24 risk 23 increased 24 risk 25 for 28 outcomes 26 poor 27 health 27 health 28 outcomes methods : cross - sectional data were from the 2008 - 2010 survey of the health of wisconsin , a representative sample of adults aged 21 - 74 years . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 4 - 1 methods 2 : 2 : 3 cross 4 - 6 data 4 - 7 were 5 sectional 6 data 6 data 7 were 7 were 8 from 8 from 13 survey 9 the 11 - 10 2008 11 - 11 - 12 2010 11 - 13 survey 13 survey 14 of 13 survey 17 of 14 of 16 health 15 the 16 health 17 of 18 wisconsin 18 wisconsin 22 sample 19 , 22 sample 20 a 21 representative 20 a 22 sample 21 representative 22 sample 22 sample 23 of 22 sample 29 years 22 sample 30 . 23 of 24 adults 24 adults 25 aged 25 aged 26 21 27 - 29 years 28 74 29 years 29 years 30 . participants ( n = 1,364 ) completed questionnaires about caregiving status , sociodemographics , global stress , and hrqol . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 7 completed 0 ###LEFT-WALL### 20 . 1 participants 4 = 1 participants 7 completed 2 ( 4 = 3 n 4 = 4 = 5 1,364 4 = 6 ) 7 completed 8 questionnaires 7 completed 9 about 9 about 18 and 10 caregiving 11 status 11 status 12 , 12 , 13 sociodemographics 12 , 14 , 14 , 16 stress 14 , 18 and 15 global 16 stress 17 , 18 and 18 and 19 hrqol staged generalized additive models assessed the impact of caregiving on hrqol and the role of caregiver strain and global stress in this relationship . 0 ###LEFT-WALL### 4 models 0 ###LEFT-WALL### 5 assessed 0 ###LEFT-WALL### 24 . 1 staged 3 additive 2 generalized 3 additive 3 additive 4 models 4 models 5 assessed 5 assessed 7 impact 5 assessed 10 on 5 assessed 21 in 6 the 7 impact 7 impact 8 of 8 of 9 caregiving 10 on 18 and 11 hrqol 12 and 12 and 14 role 12 and 15 of 12 and 18 and 13 the 14 role 15 of 17 strain 16 caregiver 17 strain 18 and 20 stress 19 global 20 stress 21 in 23 relationship 22 this 23 relationship results : in the last 12 months , 17.2 % of the sample reported caregiving . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 8 , 0 ###LEFT-WALL### 16 . 1 results 2 : 2 : 3 in 3 in 7 months 4 the 5 last 4 the 6 12 6 12 7 months 8 , 10 % 8 , 14 reported 9 17.2 10 % 10 % 11 of 10 % 14 reported 11 of 13 sample 12 the 13 sample 14 reported 15 caregiving caregivers reported worse mental hrqol than [non] - caregivers ( β - 1.88 , p = 0.02 ) ; global stress mediated this relationship ( p < 0.01 ) . 0 ###LEFT-WALL### 1 caregivers 0 ###LEFT-WALL### 2 reported 0 ###LEFT-WALL### 8 - 0 ###LEFT-WALL### 30 . 1 caregivers 2 reported 2 reported 5 hrqol 2 reported 6 than 3 worse 5 hrqol 4 mental 5 hrqol 8 - 9 caregivers 8 - 19 ; 9 caregivers 11 β 9 caregivers 16 = 10 ( 11 β 11 β 12 - 13 1.88 16 = 14 , 16 = 15 p 16 = 16 = 17 0.02 16 = 18 ) 19 ; 21 stress 19 ; 22 mediated 20 global 21 stress 21 stress 22 mediated 22 mediated 24 relationship 23 this 24 relationship 24 relationship 27 < 25 ( 27 < 26 p 27 < 27 < 28 0.01 27 < 29 ) caregivers with the highest levels of strain reported worse mental and physical hrqol ( β - 7.12 , p < 0.01 ) , and caregivers with the lowest levels of strain reported better mental hrqol ( β 2.06 , p = 0.01 ) than [non] - caregivers ; these associations were attenuated by global stress ( p < 0.01 ) . 0 ###LEFT-WALL### 1 caregivers 0 ###LEFT-WALL### 24 and 0 ###LEFT-WALL### 48 ; 0 ###LEFT-WALL### 61 . 1 caregivers 2 with 1 caregivers 6 of 1 caregivers 24 and 2 with 5 levels 3 the 4 highest 3 the 5 levels 6 of 7 strain 8 reported 13 hrqol 8 reported 16 - 8 reported 24 and 9 worse 13 hrqol 10 mental 11 and 11 and 12 physical 11 and 13 hrqol 14 ( 16 - 15 β 16 - 16 - 17 7.12 16 - 22 ) 17 7.12 20 < 18 , 20 < 19 p 20 < 20 < 21 0.01 20 < 22 ) 23 , 24 and 24 and 25 caregivers 24 and 26 with 26 with 28 lowest 26 with 47 caregivers 27 the 28 lowest 28 lowest 29 levels 28 lowest 33 better 29 levels 30 of 29 levels 33 better 30 of 31 strain 31 strain 32 reported 33 better 35 hrqol 34 mental 35 hrqol 35 hrqol 37 β 36 ( 37 β 37 β 41 = 37 β 44 than 37 β 46 - 38 2.06 41 = 39 , 41 = 40 p 41 = 41 = 42 0.01 41 = 43 ) 48 ; 50 associations 48 ; 52 attenuated 49 these 50 associations 50 associations 51 were 51 were 52 attenuated 52 attenuated 53 by 52 attenuated 58 < 53 by 55 stress 54 global 55 stress 56 ( 58 < 57 p 58 < 58 < 59 0.01 58 < 60 ) conclusion : global stress , rather than caregiving per se , contributes to poor hrqol among caregivers [,] above and beyond the effect of caregiving strain . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 4 stress 2 : 12 contributes 2 : 27 . 3 global 4 stress 4 stress 12 contributes 5 , 7 than 6 rather 7 than 7 than 8 caregiving 7 than 11 , 7 than 12 contributes 8 caregiving 10 se 9 per 10 se 12 contributes 13 to 12 contributes 16 among 12 contributes 20 and 13 to 15 hrqol 14 poor 15 hrqol 16 among 17 caregivers 19 above 20 and 20 and 21 beyond 21 beyond 23 effect 22 the 23 effect 23 effect 24 of 24 of 25 caregiving 25 caregiving 26 strain screening , monitoring , and reducing stress in multiple life domains presents an opportunity to improve hrqol outcomes for caregivers . 0 ###LEFT-WALL### 7 stress 0 ###LEFT-WALL### 12 presents 0 ###LEFT-WALL### 21 . 1 screening 2 , 2 , 3 monitoring 2 , 5 and 4 , 5 and 5 and 6 reducing 5 and 7 stress 7 stress 8 in 7 stress 12 presents 8 in 11 domains 9 multiple 10 life 10 life 11 domains 12 presents 14 opportunity 13 an 14 opportunity 14 opportunity 15 to 14 opportunity 16 improve 15 to 16 improve 16 improve 18 outcomes 17 hrqol 18 outcomes 18 outcomes 19 for 19 for 20 caregivers background : as the prevalence of chronic disease amongst older workers is high and increasing , it is important to know if the large subgroup of older workers with chronic disease has specific needs when it comes to prolonging participation in paid work . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 44 . 2 : 17 it 2 : 18 is 2 : 21 know 3 as 5 prevalence 3 as 12 is 3 as 16 , 3 as 17 it 4 the 5 prevalence 5 prevalence 6 of 5 prevalence 12 is 6 of 8 disease 7 chronic 8 disease 8 disease 9 amongst 9 amongst 11 workers 10 older 11 workers 12 is 14 and 13 high 14 and 14 and 15 increasing 17 it 18 is 18 is 19 important 19 important 20 to 20 to 21 know 21 know 22 if 21 know 35 when 21 know 38 to 21 know 41 in 22 if 25 subgroup 22 if 32 has 23 the 25 subgroup 24 large 25 subgroup 25 subgroup 26 of 25 subgroup 29 with 25 subgroup 32 has 26 of 28 workers 27 older 28 workers 29 with 31 disease 30 chronic 31 disease 32 has 34 needs 33 specific 34 needs 35 when 36 it 35 when 37 comes 36 it 37 comes 38 to 39 prolonging 39 prolonging 40 participation 41 in 43 work 42 paid 43 work objectives : to investigate differences and similarities in predictors of having paid work in workers aged 55+ with and without chronic disease . 0 ###LEFT-WALL### 1 objectives 0 ###LEFT-WALL### 2 : 2 : 3 to 2 : 4 investigate 2 : 23 . 3 to 4 investigate 4 investigate 6 and 4 investigate 19 and 5 differences 6 and 6 and 7 similarities 8 in 9 predictors 8 in 19 and 9 predictors 10 of 9 predictors 15 workers 9 predictors 18 with 10 of 11 having 11 having 12 paid 12 paid 13 work 12 paid 14 in 15 workers 16 aged 16 aged 17 55+ 16 aged 18 with 19 and 20 without 20 without 22 disease 21 chronic 22 disease methods : workers aged 55 - 62 years were selected from the 2002 - 2003 cohort of the longitudinal aging study amsterdam ( n = 333 ) . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 28 . 2 : 3 workers 3 workers 4 aged 3 workers 17 of 4 aged 6 - 4 aged 11 from 5 55 6 - 6 - 7 62 7 62 8 years 8 years 9 were 9 were 10 selected 11 from 16 cohort 12 the 16 cohort 13 2002 14 - 14 - 15 2003 14 - 16 cohort 17 of 22 amsterdam 18 the 22 amsterdam 19 longitudinal 20 aging 20 aging 21 study 21 study 22 amsterdam 22 amsterdam 25 = 23 ( 25 = 24 n 25 = 25 = 26 333 25 = 27 ) potential predictors were : health , personality , work characteristics , and demographics . 0 ###LEFT-WALL### 1 potential 0 ###LEFT-WALL### 3 were 0 ###LEFT-WALL### 4 : 1 potential 3 were 2 predictors 3 were 4 : 12 and 4 : 14 . 5 health 6 , 6 , 7 personality 6 , 8 , 8 , 10 characteristics 8 , 12 and 9 work 10 characteristics 11 , 12 and 12 and 13 demographics [per] potential predictor , a logistic regression coefficient for ['] having paid work in 2005 - 2006 ['] was calculated for workers [with] and without chronic disease . 0 ###LEFT-WALL### 3 predictor 0 ###LEFT-WALL### 20 calculated 2 potential 3 predictor 4 , 20 calculated 5 a 6 logistic 5 a 8 coefficient 6 logistic 7 regression 7 regression 8 coefficient 8 coefficient 9 for 8 coefficient 13 work 8 coefficient 19 was 8 coefficient 20 calculated 9 for 11 having 11 having 12 paid 13 work 14 in 13 work 19 was 14 in 16 - 15 2005 16 - 16 - 17 2006 20 calculated 24 and 20 calculated 28 . 21 for 22 workers 21 for 24 and 24 and 25 without 25 without 27 disease 26 chronic 27 disease a pooled estimate was computed and differences between the pooled estimate and the coefficients were tested . 0 ###LEFT-WALL### 3 estimate 0 ###LEFT-WALL### 5 computed 0 ###LEFT-WALL### 6 and 0 ###LEFT-WALL### 17 . 1 a 3 estimate 2 pooled 3 estimate 3 estimate 4 was 4 was 5 computed 6 and 7 differences 6 and 16 tested 7 differences 8 between 7 differences 15 were 8 between 12 and 9 the 11 estimate 10 pooled 11 estimate 11 estimate 12 and 12 and 14 coefficients 13 the 14 coefficients 15 were 16 tested results follow - up data were available for 95 % , of whom 67 % still had paid work . 0 ###LEFT-WALL### 2 follow 0 ###LEFT-WALL### 3 - 1 results 2 follow 3 - 5 data 3 - 6 were 4 up 5 data 5 data 6 were 6 were 7 available 7 available 8 for 8 for 10 % 9 95 10 % 10 % 12 of 11 , 12 of 12 of 13 whom 12 of 20 . 13 whom 15 % 13 whom 18 paid 14 67 15 % 15 % 17 had 16 still 17 had 17 had 18 paid 18 paid 19 work predictors of having paid work were similar for workers [with] and without chronic diseases , except for physical workload [(] χ ( 2 ) = 5.37 [;] df [=] 1 [ )(and psychosocial resources at work ( χ ( 2 [ )(= 5.94 [;] [df] = 1 ) . 0 ###LEFT-WALL### 1 predictors 0 ###LEFT-WALL### 11 and 1 predictors 2 of 1 predictors 6 were 2 of 3 having 3 having 4 paid 4 paid 5 work 6 were 7 similar 7 similar 8 for 8 for 9 workers 11 and 21 χ 12 without 14 diseases 12 without 15 , 12 without 21 χ 13 chronic 14 diseases 16 except 17 for 16 except 21 χ 17 for 19 workload 18 physical 19 workload 21 χ 23 2 21 χ 25 = 22 ( 23 2 23 2 24 ) 25 = 32 )(and 25 = 35 at 26 5.37 28 df 28 df 30 1 28 df 32 )(and 32 )(and 34 resources 33 psychosocial 34 resources 35 at 36 work 36 work 38 χ 37 ( 38 χ 38 χ 42 )(= 38 χ 46 = 38 χ 49 . 39 ( 42 )(= 40 2 42 )(= 42 )(= 46 = 43 5.94 46 = 46 = 47 1 46 = 48 ) having more psychosocial resources [(] or = 3.57 ; 95 %ci 1.33 - 10.0 ) was predictive for having paid work in workers with chronic disease and not in workers without chronic disease . 0 ###LEFT-WALL### 1 having 0 ###LEFT-WALL### 7 = 0 ###LEFT-WALL### 9 ; 0 ###LEFT-WALL### 34 . 1 having 6 or 1 having 7 = 2 more 3 psychosocial 3 psychosocial 4 resources 4 resources 6 or 7 = 8 3.57 9 ; 11 %ci 9 ; 20 paid 10 95 11 %ci 11 %ci 12 1.33 11 %ci 14 10.0 11 %ci 16 was 13 - 14 10.0 14 10.0 15 ) 16 was 17 predictive 17 predictive 18 for 18 for 19 having 19 having 20 paid 20 paid 21 work 20 paid 22 in 20 paid 27 and 22 in 23 workers 24 with 26 disease 24 with 27 and 25 chronic 26 disease 27 and 28 not 27 and 29 in 29 in 30 workers 30 workers 31 without 31 without 33 disease 32 chronic 33 disease lower age , more weekly working hours , no functional limitations , fewer depressive symptoms , lower neuroticism scores , and more sense of mastery were significantly associated with having paid work in all workers . 0 ###LEFT-WALL### 21 and 0 ###LEFT-WALL### 30 having 0 ###LEFT-WALL### 36 . 1 lower 2 age 2 age 3 , 3 , 7 hours 3 , 21 and 4 more 5 weekly 5 weekly 7 hours 6 working 7 hours 7 hours 11 limitations 7 hours 15 symptoms 8 , 11 limitations 9 no 11 limitations 10 functional 11 limitations 11 limitations 12 , 12 , 15 symptoms 13 fewer 15 symptoms 14 depressive 15 symptoms 15 symptoms 19 scores 15 symptoms 20 , 16 , 19 scores 17 lower 18 neuroticism 18 neuroticism 19 scores 19 scores 20 , 21 and 23 sense 21 and 24 of 21 and 26 were 22 more 23 sense 24 of 25 mastery 26 were 28 associated 27 significantly 28 associated 28 associated 29 with 29 with 30 having 30 having 32 work 31 paid 32 work 32 work 33 in 33 in 35 workers 34 all 35 workers conclusions : differences between predictors of having paid work between workers [with] and without chronic disease should be taken into account when aiming to [prevent] exit from the workforce . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 3 differences 2 : 19 taken 2 : 30 . 3 differences 4 between 3 differences 6 of 3 differences 17 should 4 between 5 predictors 6 of 7 having 7 having 9 work 8 paid 9 work 9 work 13 and 10 between 11 workers 10 between 13 and 13 and 14 without 14 without 16 disease 15 chronic 16 disease 17 should 18 be 18 be 19 taken 19 taken 21 account 19 taken 22 when 20 into 21 account 22 when 23 aiming 23 aiming 24 to 23 aiming 26 exit 24 to 26 exit 26 exit 27 from 27 from 29 workforce 28 the 29 workforce in particular the vulnerable subgroup of older workers with chronic disease and low psychosocial resources at work is more likely to quit working . 0 ###LEFT-WALL### 5 subgroup 0 ###LEFT-WALL### 18 is 0 ###LEFT-WALL### 24 . 1 in 2 particular 2 particular 5 subgroup 3 the 5 subgroup 4 vulnerable 5 subgroup 5 subgroup 6 of 5 subgroup 16 at 5 subgroup 18 is 6 of 12 and 7 older 8 workers 8 workers 9 with 8 workers 12 and 9 with 11 disease 10 chronic 11 disease 12 and 15 resources 13 low 15 resources 14 psychosocial 15 resources 16 at 17 work 18 is 20 likely 19 more 20 likely 20 likely 21 to 20 likely 22 quit 21 to 22 quit 22 quit 23 working the klotho gene is a suppressor of the aging phenomena , and the secretion as well as the circulation of klotho proteins decrease with aging . 0 ###LEFT-WALL### 3 gene 0 ###LEFT-WALL### 4 is 0 ###LEFT-WALL### 26 . 1 the 3 gene 2 klotho 3 gene 3 gene 4 is 4 is 6 suppressor 4 is 17 as 5 a 6 suppressor 6 suppressor 7 of 7 of 12 and 8 the 10 phenomena 9 aging 10 phenomena 10 phenomena 12 and 11 , 12 and 12 and 14 secretion 13 the 14 secretion 15 as 16 well 16 well 17 as 17 as 19 circulation 18 the 19 circulation 19 circulation 20 of 19 circulation 22 proteins 19 circulation 25 aging 20 of 21 klotho 22 proteins 23 decrease 23 decrease 24 with 24 with 25 aging although habitual exercise has antiaging effects ( e.g [.] , a decrease in arterial stiffness ) , the relationship between klotho and habitual exercise remains unclear . 0 ###LEFT-WALL### 19 relationship 0 ###LEFT-WALL### 25 remains 0 ###LEFT-WALL### 27 . 1 although 3 exercise 1 although 4 has 1 although 17 , 1 although 19 relationship 2 habitual 3 exercise 3 exercise 4 has 4 has 6 effects 5 antiaging 6 effects 6 effects 8 e.g 7 ( 8 e.g 8 e.g 12 decrease 8 e.g 17 , 10 , 12 decrease 11 a 12 decrease 12 decrease 13 in 12 decrease 16 ) 13 in 15 stiffness 14 arterial 15 stiffness 18 the 19 relationship 19 relationship 20 between 19 relationship 25 remains 20 between 22 and 21 klotho 22 and 22 and 24 exercise 23 habitual 24 exercise 25 remains 26 unclear in the present study , we investigated the effect of habitual exercise on klotho , with a particular focus on arterial stiffness . 0 ###LEFT-WALL### 6 we 0 ###LEFT-WALL### 7 investigated 1 in 4 study 1 in 5 , 1 in 6 we 2 the 4 study 3 present 4 study 6 we 7 investigated 7 investigated 9 effect 7 investigated 13 on 8 the 9 effect 9 effect 10 of 10 of 12 exercise 11 habitual 12 exercise 13 on 14 klotho 14 klotho 16 with 15 , 16 with 16 with 19 focus 16 with 23 . 17 a 18 particular 17 a 19 focus 18 particular 19 focus 19 focus 20 on 20 on 22 stiffness 21 arterial 22 stiffness first , we examined the correlation between plasma klotho concentration and arterial stiffness ( carotid artery compliance and β - stiffness index ) or aerobic exercise capacity [ oxygen uptake at ventilatory [threshold] ( vt ) ] in 69 healthy , postmenopausal women ( 50 - 76 years old ) by conducting a cross - sectional study . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 examined 0 ###LEFT-WALL### 55 - 0 ###LEFT-WALL### 58 . 1 first 2 , 1 first 3 we 3 we 4 examined 4 examined 24 or 4 examined 38 in 4 examined 51 by 5 the 6 correlation 6 correlation 7 between 6 correlation 24 or 7 between 11 and 8 plasma 10 concentration 9 klotho 10 concentration 10 concentration 11 and 11 and 13 stiffness 11 and 18 and 12 arterial 13 stiffness 14 ( 18 and 15 carotid 17 compliance 16 artery 17 compliance 17 compliance 18 and 18 and 22 index 18 and 23 ) 19 β 20 - 19 β 21 stiffness 21 stiffness 22 index 24 or 27 capacity 24 or 30 uptake 25 aerobic 26 exercise 26 exercise 27 capacity 28 [ 30 uptake 29 oxygen 30 uptake 30 uptake 31 at 30 uptake 35 vt 30 uptake 37 ] 31 at 32 ventilatory 34 ( 35 vt 35 vt 36 ) 38 in 43 women 39 69 43 women 40 healthy 41 , 40 healthy 43 women 42 postmenopausal 43 women 43 women 49 old 44 ( 49 old 45 50 46 - 46 - 47 76 46 - 48 years 48 years 49 old 49 old 50 ) 51 by 52 conducting 52 conducting 54 cross 53 a 54 cross 55 - 57 study 56 sectional 57 study second , we tested the effects of aerobic exercise training on plasma klotho concentrations and arterial stiffness . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 tested 0 ###LEFT-WALL### 18 . 1 second 2 , 1 second 3 we 3 we 4 tested 4 tested 6 effects 4 tested 11 on 5 the 6 effects 6 effects 7 of 7 of 10 training 8 aerobic 9 exercise 9 exercise 10 training 11 on 15 and 12 plasma 14 concentrations 13 klotho 14 concentrations 14 concentrations 15 and 15 and 17 stiffness 16 arterial 17 stiffness a total of 19 healthy , postmenopausal women ( 50 - 76 years old ) were divided into two groups : control group and exercise group . 0 ###LEFT-WALL### 2 total 0 ###LEFT-WALL### 17 divided 0 ###LEFT-WALL### 21 : 1 a 2 total 2 total 3 of 2 total 16 were 3 of 8 women 4 19 8 women 5 healthy 6 , 5 healthy 8 women 7 postmenopausal 8 women 8 women 10 50 8 women 14 old 9 ( 10 50 10 50 11 - 11 - 14 old 12 76 13 years 13 years 14 old 14 old 15 ) 16 were 17 divided 17 divided 18 into 18 into 20 groups 19 two 20 groups 21 : 24 and 21 : 26 group 21 : 27 . 22 control 23 group 23 group 24 and 24 and 25 exercise 24 and 26 group the exercise group completed 12 wk of moderate aerobic exercise training . 0 ###LEFT-WALL### 3 group 0 ###LEFT-WALL### 4 completed 0 ###LEFT-WALL### 12 . 1 the 3 group 2 exercise 3 group 3 group 4 completed 4 completed 6 wk 5 12 6 wk 6 wk 7 of 7 of 11 training 8 moderate 10 exercise 9 aerobic 10 exercise 10 exercise 11 training in the cross - sectional study , plasma klotho concentrations positively correlated with carotid artery compliance and vt and negatively correlated with the β - stiffness index . 0 ###LEFT-WALL### 10 concentrations 0 ###LEFT-WALL### 19 and 0 ###LEFT-WALL### 28 . 1 in 3 cross 1 in 7 , 1 in 10 concentrations 2 the 3 cross 3 cross 6 study 4 - 6 study 5 sectional 6 study 6 study 7 , 8 plasma 10 concentrations 9 klotho 10 concentrations 10 concentrations 19 and 11 positively 12 correlated 12 correlated 13 with 12 correlated 19 and 13 with 17 and 14 carotid 16 compliance 15 artery 16 compliance 16 compliance 17 and 17 and 18 vt 19 and 21 correlated 19 and 22 with 20 negatively 21 correlated 22 with 27 index 23 the 27 index 24 β 25 - 24 β 26 stiffness 26 stiffness 27 index in the interventional study , aerobic exercise training increased plasma klotho concentrations and carotid artery compliance and decreased the β - stiffness index . 0 ###LEFT-WALL### 8 training 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 24 . 1 in 4 study 1 in 5 , 1 in 8 training 2 the 4 study 3 interventional 4 study 6 aerobic 7 exercise 7 exercise 8 training 8 training 17 and 9 increased 13 and 9 increased 17 and 10 plasma 12 concentrations 11 klotho 12 concentrations 12 concentrations 13 and 13 and 16 compliance 14 carotid 16 compliance 15 artery 16 compliance 17 and 18 decreased 18 decreased 23 index 19 the 23 index 20 β 21 - 20 β 22 stiffness 22 stiffness 23 index moreover , the changes in plasma klotho concentration and arterial stiffness were found to be correlated . 0 ###LEFT-WALL### 4 changes 0 ###LEFT-WALL### 13 found 0 ###LEFT-WALL### 17 . 1 moreover 2 , 1 moreover 4 changes 3 the 4 changes 4 changes 5 in 4 changes 12 were 5 in 9 and 6 plasma 8 concentration 7 klotho 8 concentration 8 concentration 9 and 9 and 11 stiffness 10 arterial 11 stiffness 12 were 13 found 13 found 14 to 14 to 15 be 15 be 16 correlated these results suggest a possible role for secreted klotho in the exercise - induced modulation of arterial stiffness . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 suggest 0 ###LEFT-WALL### 13 - 0 ###LEFT-WALL### 19 . 1 these 2 results 2 results 3 suggest 3 suggest 6 role 3 suggest 10 in 4 a 5 possible 4 a 6 role 5 possible 6 role 6 role 7 for 7 for 9 klotho 8 secreted 9 klotho 10 in 12 exercise 11 the 12 exercise 13 - 15 modulation 14 induced 15 modulation 15 modulation 16 of 16 of 18 stiffness 17 arterial 18 stiffness importance : in the coming decades , the population of older adults with type 2 diabetes mellitus is expected to grow substantially . 0 ###LEFT-WALL### 1 importance 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 7 , 0 ###LEFT-WALL### 23 . 1 importance 2 : 2 : 3 in 3 in 6 decades 4 the 6 decades 5 coming 6 decades 7 , 9 population 7 , 19 expected 8 the 9 population 9 population 10 of 9 population 18 is 10 of 12 adults 11 older 12 adults 12 adults 13 with 13 with 17 mellitus 14 type 16 diabetes 15 2 16 diabetes 16 diabetes 17 mellitus 18 is 19 expected 19 expected 20 to 19 expected 21 grow 20 to 21 grow 21 grow 22 substantially understanding the clinical course of diabetes in this population is critical for establishing evidence - based clinical practice recommendations , identifying research priorities , allocating resources , and setting health care policies . 0 ###LEFT-WALL### 1 understanding 0 ###LEFT-WALL### 10 is 1 understanding 4 course 1 understanding 10 is 2 the 4 course 3 clinical 4 course 4 course 5 of 4 course 7 in 5 of 6 diabetes 7 in 9 population 8 this 9 population 10 is 11 critical 11 critical 12 for 11 critical 25 allocating 12 for 13 establishing 13 establishing 14 evidence 13 establishing 21 identifying 14 evidence 19 recommendations 15 - 19 recommendations 16 based 18 practice 17 clinical 18 practice 18 practice 19 recommendations 19 recommendations 20 , 20 , 21 identifying 21 identifying 23 priorities 21 identifying 24 , 22 research 23 priorities 24 , 25 allocating 25 allocating 32 policies 25 allocating 33 . 26 resources 28 and 27 , 28 and 28 and 31 care 28 and 32 policies 29 setting 30 health 30 health 31 care objective to contrast the rates of diabetes complications and mortality across age and diabetes duration categories . 0 ###LEFT-WALL### 16 categories 0 ###LEFT-WALL### 17 . 1 objective 2 to 2 to 16 categories 3 contrast 16 categories 4 the 5 rates 5 rates 6 of 5 rates 9 and 6 of 8 complications 7 diabetes 8 complications 9 and 10 mortality 9 and 11 across 9 and 13 and 11 across 12 age 13 and 14 diabetes 13 and 16 categories 15 duration 16 categories main outcomes and measures : incident acute hyperglycemic events , acute hypoglycemic events ( hypoglycemia ) , microvascular complications ( end [-] stage renal disease , peripheral vascular disease , lower limb amputation , and diabetic eye disease ) , cardiovascular complications ( coronary artery disease , cerebrovascular disease , and congestive heart failure ) , and all - cause mortality . 0 ###LEFT-WALL### 4 measures 0 ###LEFT-WALL### 5 : 0 ###LEFT-WALL### 10 , 1 main 2 outcomes 2 outcomes 3 and 3 and 4 measures 4 measures 5 : 5 : 9 events 6 incident 9 events 7 acute 9 events 8 hyperglycemic 9 events 10 , 13 events 10 , 31 lower 10 , 59 - 11 acute 13 events 12 hypoglycemic 13 events 13 events 15 hypoglycemia 13 events 19 complications 13 events 31 lower 14 ( 15 hypoglycemia 15 hypoglycemia 16 ) 17 , 19 complications 18 microvascular 19 complications 19 complications 25 disease 19 complications 30 , 20 ( 25 disease 21 end 25 disease 23 stage 25 disease 24 renal 25 disease 25 disease 29 disease 25 disease 30 , 26 , 29 disease 27 peripheral 29 disease 28 vascular 29 disease 29 disease 30 , 31 lower 57 and 32 limb 33 amputation 33 amputation 35 and 34 , 35 and 35 and 38 disease 35 and 39 ) 35 and 42 complications 35 and 51 and 36 diabetic 38 disease 37 eye 38 disease 40 , 42 complications 41 cardiovascular 42 complications 42 complications 46 disease 42 complications 49 disease 42 complications 50 , 43 ( 46 disease 44 coronary 45 artery 45 artery 46 disease 46 disease 47 , 47 , 49 disease 48 cerebrovascular 49 disease 49 disease 50 , 50 , 51 and 51 and 54 failure 51 and 55 ) 51 and 57 and 52 congestive 53 heart 53 heart 54 failure 56 , 57 and 57 and 58 all 59 - 60 cause 59 - 62 . 60 cause 61 mortality results : among older adults with diabetes of short duration , cardiovascular complications followed by hypoglycemia were the most common nonfatal complications . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 11 , 0 ###LEFT-WALL### 23 . 1 results 2 : 2 : 3 among 2 : 6 with 3 among 5 adults 4 older 5 adults 6 with 7 diabetes 7 diabetes 8 of 8 of 10 duration 9 short 10 duration 11 , 13 complications 11 , 17 were 12 cardiovascular 13 complications 13 complications 14 followed 13 complications 17 were 14 followed 15 by 15 by 16 hypoglycemia 17 were 22 complications 18 the 19 most 19 most 22 complications 20 common 22 complications 21 nonfatal 22 complications [for] example , among individuals aged 70 to 79 years with a short duration of diabetes , coronary artery disease and hypoglycemia rates were higher ( 11.47 per 1000 person - years [and] 5.03 per 1000 person - years , respectively ) compared with end - stage renal disease ( 2.60 per 1000 person - years [ )(, lower limb amputation [(] 1.28 per 1000 person - years [ )(, and acute hyperglycemic events ( 0.82 per 1000 person - years ) . 0 ###LEFT-WALL### 2 example 0 ###LEFT-WALL### 3 , 3 , 14 duration 4 among 5 individuals 4 among 14 duration 5 individuals 6 aged 6 aged 7 70 8 to 10 years 8 to 14 duration 9 79 10 years 10 years 11 with 11 with 13 short 12 a 13 short 14 duration 15 of 14 duration 24 were 15 of 21 and 16 diabetes 17 , 17 , 20 disease 17 , 21 and 18 coronary 20 disease 19 artery 20 disease 21 and 23 rates 22 hypoglycemia 23 rates 24 were 25 higher 25 higher 31 - 26 ( 31 - 27 11.47 28 per 27 11.47 31 - 28 per 30 person 29 1000 30 person 31 - 32 years 32 years 34 5.03 32 years 43 compared 34 5.03 35 per 34 5.03 39 years 34 5.03 43 compared 35 per 37 person 36 1000 37 person 38 - 39 years 39 years 40 , 40 , 41 respectively 41 respectively 42 ) 41 respectively 43 compared 43 compared 44 with 44 with 45 end 44 with 56 years 45 end 49 disease 46 - 49 disease 47 stage 49 disease 48 renal 49 disease 49 disease 51 2.60 49 disease 55 - 50 ( 51 2.60 51 2.60 52 per 51 2.60 55 - 52 per 54 person 53 1000 54 person 56 years 67 - 58 )(, 67 - 59 lower 60 limb 60 limb 61 amputation 61 amputation 63 1.28 61 amputation 64 per 61 amputation 67 - 64 per 66 person 65 1000 66 person 67 - 74 events 68 years 71 and 70 )(, 71 and 71 and 72 acute 71 and 74 events 73 hyperglycemic 74 events 74 events 76 0.82 75 ( 76 0.82 76 0.82 77 per 76 0.82 81 years 76 0.82 83 . 77 per 79 person 78 1000 79 person 80 - 81 years 81 years 82 ) we observed a similar pattern among patients in the same age group with a long duration of diabetes [,] with some of the highest incidence rates in coronary artery disease and hypoglycemia ( 18.98 per 1000 person - years [and] 15.88 per 1000 person - years , respectively ) compared with end - stage renal disease ( 7.64 per 1000 person - years [ )(, lower limb amputation [(] 4.26 per 1000 person - years [ )(, and acute hyperglycemic events ( 1.76 per 1000 person - years ) . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 observed 1 we 2 observed 2 observed 5 pattern 3 a 4 similar 3 a 5 pattern 4 similar 5 pattern 5 pattern 6 among 6 among 7 patients 7 patients 8 in 7 patients 13 with 8 in 12 group 9 the 10 same 10 same 12 group 11 age 12 group 13 with 16 duration 14 a 16 duration 15 long 16 duration 16 duration 17 of 16 duration 20 with 16 duration 22 of 16 duration 27 in 17 of 18 diabetes 20 with 21 some 22 of 24 highest 23 the 24 highest 24 highest 25 incidence 24 highest 26 rates 25 incidence 26 rates 27 in 31 and 28 coronary 29 artery 29 artery 30 disease 30 disease 31 and 31 and 39 years 32 hypoglycemia 34 18.98 32 hypoglycemia 38 - 32 hypoglycemia 39 years 33 ( 34 18.98 34 18.98 35 per 34 18.98 38 - 35 per 37 person 36 1000 37 person 39 years 41 15.88 39 years 42 per 39 years 46 years 39 years 50 compared 42 per 44 person 43 1000 44 person 45 - 46 years 46 years 47 , 47 , 48 respectively 48 respectively 49 ) 48 respectively 50 compared 50 compared 51 with 51 with 52 end 51 with 63 years 52 end 56 disease 53 - 56 disease 54 stage 56 disease 55 renal 56 disease 56 disease 58 7.64 56 disease 62 - 57 ( 58 7.64 58 7.64 59 per 58 7.64 62 - 59 per 61 person 60 1000 61 person 63 years 74 - 65 )(, 74 - 66 lower 67 limb 67 limb 68 amputation 68 amputation 70 4.26 68 amputation 71 per 68 amputation 74 - 71 per 73 person 72 1000 73 person 74 - 81 events 75 years 78 and 77 )(, 78 and 78 and 79 acute 78 and 81 events 80 hyperglycemic 81 events 81 events 83 1.76 82 ( 83 1.76 83 1.76 84 per 83 1.76 88 years 83 1.76 90 . 84 per 86 person 85 1000 86 person 87 - 88 years 88 years 89 ) for a given age group , the rates of each outcome , particularly hypoglycemia and microvascular complications , increased dramatically with longer duration of the disease . 0 ###LEFT-WALL### 8 rates 0 ###LEFT-WALL### 19 increased 0 ###LEFT-WALL### 27 . 1 for 5 group 1 for 6 , 1 for 8 rates 2 a 5 group 3 given 4 age 4 age 5 group 7 the 8 rates 8 rates 9 of 8 rates 19 increased 9 of 11 outcome 10 each 11 outcome 11 outcome 15 and 12 , 13 particularly 12 , 15 and 14 hypoglycemia 15 and 15 and 17 complications 15 and 18 , 16 microvascular 17 complications 19 increased 20 dramatically 19 increased 21 with 21 with 23 duration 22 longer 23 duration 23 duration 24 of 24 of 26 disease 25 the 26 disease however , for a given duration of diabetes , rates of hypoglycemia , cardiovascular complications , and mortality increased steeply with advancing age , and rates of microvascular complications remained stable or declined . 0 ###LEFT-WALL### 25 and 0 ###LEFT-WALL### 32 or 0 ###LEFT-WALL### 34 . 1 however 17 and 1 however 19 increased 1 however 25 and 2 , 3 for 3 for 6 duration 3 for 9 , 3 for 17 and 4 a 6 duration 5 given 6 duration 6 duration 7 of 7 of 8 diabetes 10 rates 11 of 10 rates 17 and 11 of 15 complications 12 hypoglycemia 13 , 12 hypoglycemia 15 complications 14 cardiovascular 15 complications 16 , 17 and 17 and 18 mortality 17 and 19 increased 19 increased 20 steeply 19 increased 21 with 21 with 22 advancing 23 age 25 and 24 , 25 and 25 and 26 rates 25 and 27 of 25 and 32 or 27 of 29 complications 28 microvascular 29 complications 30 remained 31 stable 30 remained 32 or 32 or 33 declined conclusions and relevance : duration of diabetes and advancing age independently predict diabetes morbidity and mortality rates . 0 ###LEFT-WALL### 3 relevance 0 ###LEFT-WALL### 4 : 1 conclusions 2 and 2 and 3 relevance 4 : 8 and 4 : 12 predict 4 : 18 . 5 duration 6 of 5 duration 8 and 6 of 7 diabetes 8 and 10 age 8 and 12 predict 9 advancing 10 age 11 independently 12 predict 12 predict 15 and 13 diabetes 14 morbidity 14 morbidity 15 and 15 and 17 rates 16 mortality 17 rates as long - term survivorship with diabetes increases and as the population ages , more research and public health efforts to reduce hypoglycemia will be needed to complement ongoing efforts to reduce cardiovascular and microvascular complications . 0 ###LEFT-WALL### 24 will 0 ###LEFT-WALL### 28 complement 0 ###LEFT-WALL### 37 . 1 as 9 and 1 as 23 hypoglycemia 1 as 24 will 2 long 3 - 2 long 4 term 4 term 5 survivorship 5 survivorship 6 with 5 survivorship 8 increases 5 survivorship 9 and 6 with 7 diabetes 9 and 17 and 10 as 12 population 10 as 13 ages 10 as 14 , 10 as 17 and 11 the 12 population 12 population 13 ages 15 more 16 research 16 research 17 and 17 and 20 efforts 17 and 21 to 17 and 22 reduce 17 and 23 hypoglycemia 18 public 20 efforts 19 health 20 efforts 21 to 22 reduce 24 will 25 be 25 be 26 needed 26 needed 27 to 27 to 28 complement 28 complement 30 efforts 28 complement 31 to 29 ongoing 30 efforts 31 to 32 reduce 32 reduce 36 complications 33 cardiovascular 34 and 34 and 35 microvascular 34 and 36 complications cerebral microbleeds ( cmbs ) are considered to be a novel marker of cerebral small vessel disease . 0 ###LEFT-WALL### 2 microbleeds 0 ###LEFT-WALL### 7 considered 0 ###LEFT-WALL### 18 . 1 cerebral 2 microbleeds 2 microbleeds 4 cmbs 2 microbleeds 6 are 3 ( 4 cmbs 4 cmbs 5 ) 6 are 7 considered 7 considered 8 to 7 considered 9 be 8 to 9 be 9 be 12 marker 10 a 11 novel 10 a 12 marker 11 novel 12 marker 12 marker 13 of 13 of 17 disease 14 cerebral 16 vessel 15 small 16 vessel 16 vessel 17 disease however , the link with cognitive impairment remains unclear . 0 ###LEFT-WALL### 4 link 0 ###LEFT-WALL### 8 remains 0 ###LEFT-WALL### 10 . 1 however 2 , 1 however 4 link 3 the 4 link 4 link 5 with 4 link 8 remains 5 with 7 impairment 6 cognitive 7 impairment 8 remains 9 unclear we investigated whether cmbs - [independent] of other traditional markers of cerebral small vessel disease - are related to cognition . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 investigated 0 ###LEFT-WALL### 21 . 1 we 2 investigated 2 investigated 3 whether 3 whether 4 cmbs 3 whether 18 related 4 cmbs 7 of 4 cmbs 17 are 5 - 7 of 7 of 10 markers 7 of 16 - 8 other 10 markers 9 traditional 10 markers 10 markers 11 of 11 of 15 disease 12 cerebral 14 vessel 13 small 14 vessel 14 vessel 15 disease 17 are 18 related 18 related 19 to 19 to 20 cognition chinese subjects from the population - based singapore chinese eye study , who failed [an] initial cognitive screening and were recruited into the ongoing epidemiology of dementia in singapore study , underwent neuropsychological testing and 3 t brain magnetic resonance imaging . 0 ###LEFT-WALL### 2 subjects 0 ###LEFT-WALL### 31 , 0 ###LEFT-WALL### 42 . 1 chinese 2 subjects 2 subjects 3 from 2 subjects 13 who 2 subjects 14 failed 2 subjects 19 and 3 from 5 population 4 the 5 population 5 population 11 study 6 - 11 study 7 based 9 chinese 8 singapore 9 chinese 9 chinese 11 study 10 eye 11 study 11 study 12 , 13 who 14 failed 16 initial 18 screening 16 initial 19 and 17 cognitive 18 screening 19 and 20 were 20 were 31 , 21 recruited 22 into 21 recruited 25 epidemiology 21 recruited 28 in 21 recruited 31 , 22 into 24 ongoing 23 the 24 ongoing 25 epidemiology 26 of 26 of 27 dementia 28 in 30 study 29 singapore 30 study 31 , 32 underwent 32 underwent 35 and 33 neuropsychological 34 testing 34 testing 35 and 35 and 41 imaging 36 3 37 t 37 t 41 imaging 38 brain 41 imaging 39 magnetic 40 resonance 40 resonance 41 imaging the presence and number of cmbs were graded using brain observer microbleed scale on susceptibility - weighted images . 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 8 graded 0 ###LEFT-WALL### 16 - 1 the 2 presence 2 presence 3 and 3 and 4 number 3 and 5 of 3 and 7 were 5 of 6 cmbs 7 were 8 graded 8 graded 9 using 9 using 13 scale 9 using 14 on 10 brain 11 observer 11 observer 12 microbleed 12 microbleed 13 scale 14 on 15 susceptibility 16 - 18 images 16 - 19 . 17 weighted 18 images other magnetic resonance imaging lesions that were graded included presence of lacunes , white matter lesion , and total brain volumes . 0 ###LEFT-WALL### 18 and 0 ###LEFT-WALL### 22 . 1 other 3 resonance 2 magnetic 3 resonance 3 resonance 4 imaging 3 resonance 13 , 4 imaging 5 lesions 5 lesions 6 that 5 lesions 7 were 6 that 7 were 7 were 10 presence 8 graded 10 presence 9 included 10 presence 10 presence 11 of 11 of 12 lacunes 13 , 16 lesion 13 , 18 and 14 white 16 lesion 15 matter 16 lesion 17 , 18 and 18 and 21 volumes 19 total 21 volumes 20 brain 21 volumes a comprehensive neuropsychological battery was administered [and] cognitive function was summarized as composite and domain - specific [z] - scores . 0 ###LEFT-WALL### 9 function 0 ###LEFT-WALL### 11 summarized 0 ###LEFT-WALL### 16 - 0 ###LEFT-WALL### 21 . 1 a 2 comprehensive 1 a 9 function 2 comprehensive 4 battery 3 neuropsychological 4 battery 4 battery 5 was 5 was 6 administered 8 cognitive 9 function 9 function 10 was 10 was 11 summarized 11 summarized 12 as 12 as 14 and 13 composite 14 and 14 and 15 domain 16 - 20 scores 17 specific 19 - 17 specific 20 scores among 282 subjects , 91 had any cmbs ( 32.3 % ) , of whom 36 ( 12.8 % ) had [multiple] [cmbs] . 0 ###LEFT-WALL### 5 91 0 ###LEFT-WALL### 6 had 1 among 3 subjects 1 among 4 , 1 among 5 91 2 282 3 subjects 5 91 6 had 6 had 8 cmbs 7 any 8 cmbs 8 cmbs 11 % 8 cmbs 14 of 9 ( 11 % 10 32.3 11 % 11 % 12 ) 13 , 14 of 14 of 15 whom 14 of 24 . 15 whom 16 36 15 whom 21 had 16 36 19 % 16 36 21 had 17 ( 19 % 18 12.8 19 % 19 % 20 ) cmbs were - independent of cardiovascular risk factors and other markers of cerebral small vessel disease - significantly associated with poorer cognitive function as reflected by composite z - score [(] mean difference per cmb increase : - 0.06 [;] 95 % confidence interval : - 0.11 [,] - 0.01 ] [and] with domain - [specific] z - scores including executive function , attention , and visuoconstruction . 0 ###LEFT-WALL### 1 cmbs 0 ###LEFT-WALL### 2 were 0 ###LEFT-WALL### 3 - 1 cmbs 2 were 3 - 4 independent 4 independent 5 of 4 independent 12 of 5 of 9 and 6 cardiovascular 8 factors 7 risk 8 factors 8 factors 9 and 9 and 11 markers 10 other 11 markers 12 of 16 disease 13 cerebral 15 vessel 14 small 15 vessel 15 vessel 16 disease 16 disease 19 associated 17 - 18 significantly 17 - 19 associated 19 associated 20 with 19 associated 26 by 20 with 23 function 21 poorer 23 function 22 cognitive 23 function 23 function 25 reflected 24 as 25 reflected 26 by 27 composite 27 composite 28 z 27 composite 38 - 29 - 38 - 30 score 32 mean 32 mean 33 difference 32 mean 37 : 32 mean 38 - 33 difference 34 per 33 difference 37 : 34 per 36 increase 35 cmb 36 increase 38 - 43 confidence 39 0.06 43 confidence 41 95 42 % 42 % 43 confidence 43 confidence 44 interval 43 confidence 45 : 44 interval 45 : 45 : 49 - 45 : 53 with 46 - 49 - 47 0.11 49 - 49 - 50 0.01 49 - 51 ] 53 with 54 domain 53 with 60 including 54 domain 58 - 55 - 58 - 57 z 58 - 58 - 59 scores 60 including 62 function 61 executive 62 function 62 function 66 and 63 , 66 and 64 attention 66 and 65 , 66 and 66 and 67 visuoconstruction 66 and 68 . among chinese subjects cmbs were [,] [independent] of other concomitant markers of cerebral small vessel disease , associated [with] poorer cognitive function . 0 ###LEFT-WALL### 4 cmbs 0 ###LEFT-WALL### 5 were 0 ###LEFT-WALL### 17 , 0 ###LEFT-WALL### 23 . 1 among 3 subjects 1 among 4 cmbs 2 chinese 3 subjects 4 cmbs 5 were 5 were 8 of 8 of 11 markers 9 other 11 markers 10 concomitant 11 markers 11 markers 12 of 12 of 16 disease 13 cerebral 15 vessel 14 small 15 vessel 15 vessel 16 disease 17 , 22 function 18 associated 22 function 20 poorer 22 function 21 cognitive 22 function objective : the aims of this study [were] to evaluate and contrast the physical attributes that are associated with self - reported [vs] [.] observed ability to walk 400 m among older adults . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 2 : 20 self 2 : 22 reported 3 the 4 aims 4 aims 5 of 4 aims 11 and 5 of 7 study 6 this 7 study 7 study 9 to 7 study 10 evaluate 9 to 10 evaluate 11 and 12 contrast 11 and 15 attributes 11 and 19 with 11 and 20 self 13 the 15 attributes 14 physical 15 attributes 15 attributes 16 that 15 attributes 17 are 15 attributes 18 associated 16 that 17 are 18 associated 19 with 21 - 22 reported 22 reported 26 ability 22 reported 34 . 25 observed 26 ability 26 ability 27 to 26 ability 28 walk 27 to 28 walk 28 walk 30 m 28 walk 31 among 29 400 30 m 31 among 33 adults 32 older 33 adults design : analysis of baseline and 3 - [yr] data from 1026 participants 65 [yrs] or older in the inchianti ( invecchiare in chianti ) study was conducted . 0 ###LEFT-WALL### 1 design 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 6 and 0 ###LEFT-WALL### 28 conducted 0 ###LEFT-WALL### 29 . 1 design 2 : 2 : 3 analysis 3 analysis 4 of 4 of 5 baseline 6 and 7 3 6 and 8 - 7 3 8 - 8 - 26 study 10 data 11 from 10 data 16 or 11 from 13 participants 12 1026 13 participants 13 participants 14 65 16 or 17 older 16 or 26 study 17 older 18 in 18 in 20 inchianti 19 the 20 inchianti 20 inchianti 22 invecchiare 21 ( 22 invecchiare 22 invecchiare 23 in 22 invecchiare 25 ) 23 in 24 chianti 26 study 27 was 27 was 28 conducted observed and [self] - reported ability to walk 400 m at baseline and at 3 yrs were primary outcomes . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 20 . 1 observed 2 and 2 and 17 were 4 - 5 reported 5 reported 6 ability 5 reported 17 were 6 ability 7 to 6 ability 8 walk 7 to 8 walk 8 walk 10 m 9 400 10 m 10 m 13 and 11 at 12 baseline 11 at 13 and 13 and 14 at 14 at 16 yrs 15 3 16 yrs 17 were 19 outcomes 18 primary 19 outcomes predictors included leg speed , leg strength , leg strength symmetry , range of motion , balance , and kyphosis . 0 ###LEFT-WALL### 1 predictors 0 ###LEFT-WALL### 2 included 0 ###LEFT-WALL### 16 , 0 ###LEFT-WALL### 21 . 1 predictors 2 included 2 included 4 speed 3 leg 4 speed 4 speed 7 strength 4 speed 11 symmetry 4 speed 13 range 5 , 7 strength 6 leg 7 strength 7 strength 8 , 8 , 11 symmetry 9 leg 11 symmetry 10 strength 11 symmetry 11 symmetry 12 , 12 , 13 range 13 range 14 of 13 range 16 , 14 of 15 motion 16 , 19 and 17 balance 19 and 18 , 19 and 19 and 20 kyphosis results : balance , leg speed , leg strength , kyphosis , leg strength symmetry , and knee range of motion were associated with self - reported ability to walk 400 m at baseline ( p < 0.001 , c = 0.85 ) . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 25 self 2 : 27 reported 2 : 44 . 3 balance 6 speed 3 balance 17 and 4 , 6 speed 5 leg 6 speed 6 speed 9 strength 6 speed 16 , 7 , 9 strength 8 leg 9 strength 9 strength 11 kyphosis 9 strength 16 , 10 , 11 kyphosis 11 kyphosis 15 symmetry 11 kyphosis 16 , 12 , 15 symmetry 13 leg 14 strength 14 strength 15 symmetry 15 symmetry 16 , 17 and 18 knee 17 and 19 range 17 and 24 with 17 and 25 self 19 range 20 of 19 range 22 were 20 of 21 motion 22 were 23 associated 23 associated 24 with 26 - 27 reported 27 reported 28 ability 28 ability 29 to 28 ability 30 walk 28 ability 41 = 29 to 30 walk 30 walk 32 m 30 walk 37 < 31 400 32 m 32 m 33 at 33 at 34 baseline 35 ( 37 < 36 p 37 < 37 < 38 0.001 37 < 39 , 39 , 41 = 40 c 41 = 41 = 42 0.85 41 = 43 ) balance , leg speed , and knee range of motion were associated with observed 400 - m [walk] ( p < 0.001 , c = 0.85 ) at baseline . 0 ###LEFT-WALL### 14 observed 1 balance 2 , 2 , 4 speed 2 , 6 and 3 leg 4 speed 5 , 6 and 6 and 7 knee 6 and 8 range 6 and 13 with 6 and 14 observed 8 range 9 of 8 range 11 were 9 of 10 motion 11 were 12 associated 12 associated 13 with 14 observed 21 < 14 observed 25 = 14 observed 28 at 14 observed 30 . 15 400 16 - 16 - 17 m 16 - 21 < 19 ( 21 < 20 p 21 < 21 < 22 0.001 21 < 23 , 23 , 25 = 24 c 25 = 25 = 26 0.85 25 = 27 ) 28 at 29 baseline prospectively , baseline leg speed and leg strength were [predictive] of both [self] - reported ( p < 0.001 , c = 0.79 ) and observed ( p < 0.001 , c = 0.72 ) ability to walk 400 m at 3 yrs . 0 ###LEFT-WALL### 6 and 0 ###LEFT-WALL### 25 and 0 ###LEFT-WALL### 44 . 1 prospectively 2 , 1 prospectively 6 and 3 baseline 5 speed 4 leg 5 speed 5 speed 6 and 6 and 8 strength 6 and 25 and 7 leg 8 strength 9 were 11 of 9 were 15 reported 9 were 22 = 9 were 25 and 11 of 12 both 14 - 15 reported 15 reported 18 < 15 reported 20 , 16 ( 18 < 17 p 18 < 18 < 19 0.001 18 < 20 , 20 , 22 = 21 c 22 = 22 = 23 0.79 22 = 24 ) 25 and 26 observed 25 and 29 < 25 and 33 = 25 and 36 ability 27 ( 29 < 28 p 29 < 29 < 30 0.001 29 < 31 , 32 c 33 = 33 = 34 0.72 33 = 35 ) 36 ability 37 to 36 ability 38 walk 37 to 38 walk 38 walk 40 m 38 walk 41 at 39 400 40 m 41 at 43 yrs 42 3 43 yrs conclusions : the profiles of attributes that are associated [with] self [-] reported [vs] [.] observed walking ability differ . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 4 profiles 2 : 19 differ 2 : 20 . 3 the 4 profiles 4 profiles 5 of 4 profiles 16 observed 4 profiles 17 walking 4 profiles 19 differ 5 of 6 attributes 6 attributes 7 that 6 attributes 8 are 7 that 8 are 8 are 9 associated 9 associated 13 reported 11 self 13 reported 17 walking 18 ability the factor most consistently associated with current and future walking ability is leg speed . 0 ###LEFT-WALL### 2 factor 0 ###LEFT-WALL### 12 is 0 ###LEFT-WALL### 15 . 1 the 2 factor 2 factor 5 associated 2 factor 12 is 3 most 4 consistently 4 consistently 5 associated 5 associated 6 with 6 with 8 and 7 current 8 and 8 and 9 future 8 and 10 walking 10 walking 11 ability 12 is 14 speed 13 leg 14 speed these results draw attention to important foci for rehabilitation . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 draw 0 ###LEFT-WALL### 10 . 1 these 2 results 2 results 3 draw 3 draw 4 attention 3 draw 5 to 5 to 7 foci 6 important 7 foci 7 foci 8 for 8 for 9 rehabilitation in 1875 m [.] raymond described a progressive muscle wasting [and] weakness in 3 individuals survivors of childhood acute poliomyelitis . 0 ###LEFT-WALL### 5 raymond 0 ###LEFT-WALL### 6 described 0 ###LEFT-WALL### 21 . 1 in 3 m 1 in 5 raymond 2 1875 3 m 5 raymond 6 described 6 described 9 muscle 7 a 8 progressive 7 a 9 muscle 8 progressive 9 muscle 9 muscle 10 wasting 10 wasting 12 weakness 10 wasting 13 in 13 in 16 survivors 14 3 16 survivors 15 individuals 16 survivors 16 survivors 17 of 17 of 20 poliomyelitis 18 childhood 20 poliomyelitis 19 acute 20 poliomyelitis jean - martin charcot suggested that the initial injury should let these guys neurons more sensitive to develop posterior spinal diseases and new weakness was the result of overuse of the affected muscles . 0 ###LEFT-WALL### 1 jean 0 ###LEFT-WALL### 2 - 2 - 4 charcot 2 - 5 suggested 2 - 34 . 3 martin 4 charcot 4 charcot 5 suggested 5 suggested 6 that 6 that 9 injury 6 that 11 let 7 the 9 injury 8 initial 9 injury 9 injury 10 should 10 should 11 let 11 let 14 neurons 12 these 14 neurons 13 guys 14 neurons 14 neurons 16 sensitive 14 neurons 22 and 14 neurons 29 overuse 14 neurons 30 of 15 more 16 sensitive 16 sensitive 17 to 16 sensitive 18 develop 17 to 18 develop 19 posterior 21 diseases 20 spinal 21 diseases 21 diseases 22 and 22 and 23 new 22 and 24 weakness 22 and 28 of 22 and 29 overuse 24 weakness 25 was 25 was 27 result 26 the 27 result 27 result 28 of 30 of 33 muscles 31 the 33 muscles 32 affected 33 muscles in 1979 , after the publication of the description given by a 57 year old patient on motor difficulties that developed after suffering of polio in childhood , there was a very significant increase of comments of other individuals with similar symptoms , reaching wedged in the 80 [s] the term of post - polio syndrome . 0 ###LEFT-WALL### 29 there 0 ###LEFT-WALL### 30 was 0 ###LEFT-WALL### 43 , 0 ###LEFT-WALL### 57 . 1 in 2 1979 1 in 29 there 2 1979 4 after 3 , 4 after 4 after 6 publication 4 after 28 , 5 the 6 publication 6 publication 7 of 7 of 9 description 8 the 9 description 9 description 10 given 9 description 24 of 10 given 11 by 10 given 17 on 10 given 22 after 11 by 16 patient 12 a 16 patient 13 57 14 year 14 year 15 old 15 old 16 patient 17 on 19 difficulties 18 motor 19 difficulties 19 difficulties 20 that 19 difficulties 21 developed 20 that 21 developed 22 after 23 suffering 24 of 25 polio 25 polio 26 in 26 in 27 childhood 29 there 30 was 30 was 34 increase 31 a 32 very 31 a 34 increase 32 very 33 significant 33 significant 34 increase 34 increase 35 of 35 of 36 comments 36 comments 37 of 37 of 39 individuals 38 other 39 individuals 39 individuals 40 with 40 with 42 symptoms 41 similar 42 symptoms 43 , 44 reaching 43 , 45 wedged 43 , 54 - 44 reaching 45 wedged 45 wedged 46 in 45 wedged 51 term 46 in 48 80 47 the 48 80 50 the 51 term 51 term 52 of 52 of 53 post 54 - 56 syndrome 55 polio 56 syndrome the term is reserved for describing the development of new neurological symptoms , especially for the development of muscle weakness , muscle atrophy and new muscle fatigue not explained by other medical causes , and appear after more than 15 years of infection acute . 0 ###LEFT-WALL### 2 term 0 ###LEFT-WALL### 35 and 0 ###LEFT-WALL### 45 . 1 the 2 term 2 term 35 and 3 is 4 reserved 3 is 35 and 4 reserved 5 for 4 reserved 15 for 5 for 6 describing 6 describing 8 development 7 the 8 development 8 development 9 of 9 of 12 symptoms 10 new 12 symptoms 11 neurological 12 symptoms 13 , 14 especially 13 , 15 for 15 for 17 development 15 for 34 , 16 the 17 development 17 development 18 of 17 development 28 not 18 of 24 and 19 muscle 20 weakness 20 weakness 21 , 21 , 23 atrophy 21 , 24 and 22 muscle 23 atrophy 24 and 27 fatigue 25 new 27 fatigue 26 muscle 27 fatigue 28 not 29 explained 29 explained 30 by 30 by 33 causes 31 other 33 causes 32 medical 33 causes 34 , 35 and 35 and 36 appear 36 appear 37 after 36 appear 39 than 36 appear 44 acute 37 after 38 more 39 than 41 years 40 15 41 years 41 years 42 of 42 of 43 infection [is] [estimated] to affect 20 to 85 % of individuals with a history of polio in childhood . 0 ###LEFT-WALL### 3 to 0 ###LEFT-WALL### 4 affect 0 ###LEFT-WALL### 18 . 3 to 4 affect 4 affect 8 % 4 affect 11 with 4 affect 16 in 5 20 6 to 6 to 7 85 6 to 8 % 8 % 9 of 9 of 10 individuals 11 with 13 history 12 a 13 history 13 history 14 of 14 of 15 polio 16 in 17 childhood [in] 2000 first described the diagnostic criteria . 0 ###LEFT-WALL### 2 2000 0 ###LEFT-WALL### 4 described 0 ###LEFT-WALL### 8 . 2 2000 4 described 3 first 4 described 4 described 7 criteria 5 the 7 criteria 6 diagnostic 7 criteria this syndrome determines a change in the functional abilities . 0 ###LEFT-WALL### 2 syndrome 0 ###LEFT-WALL### 3 determines 0 ###LEFT-WALL### 10 . 1 this 2 syndrome 2 syndrome 3 determines 3 determines 5 change 3 determines 6 in 4 a 5 change 6 in 9 abilities 7 the 9 abilities 8 functional 9 abilities [its] [pathogenesis] is unknown , may be associated with aging . 0 ###LEFT-WALL### 5 , 0 ###LEFT-WALL### 11 . 3 is 4 unknown 3 is 5 , 5 , 6 may 6 may 7 be 7 be 8 associated 8 associated 9 with 9 with 10 aging it could also be due to [an] inflammatory persistent or [be] [influenced] [by] genetic factors . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 4 be 0 ###LEFT-WALL### 16 . 1 it 2 could 2 could 4 be 3 also 4 be 4 be 6 to 5 due 6 to 6 to 15 factors 8 inflammatory 15 factors 9 persistent 10 or 10 or 14 genetic 10 or 15 factors there is no effective drug treatment , so i can only recommend symptomatic and moderate muscle training . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 8 so 1 there 2 is 2 is 6 treatment 2 is 8 so 3 no 6 treatment 4 effective 6 treatment 5 drug 6 treatment 7 , 8 so 8 so 9 i 8 so 12 recommend 8 so 18 . 9 i 10 can 10 can 12 recommend 11 only 12 recommend 12 recommend 14 and 12 recommend 16 muscle 13 symptomatic 14 and 14 and 15 moderate 14 and 16 muscle 16 muscle 17 training background : the incidence of complicated choledochocystolithiasis is increasing with the aging of society in japan . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 4 incidence 2 : 8 is 2 : 17 . 3 the 4 incidence 4 incidence 5 of 4 incidence 8 is 5 of 7 choledochocystolithiasis 6 complicated 7 choledochocystolithiasis 8 is 9 increasing 9 increasing 10 with 9 increasing 15 in 10 with 12 aging 11 the 12 aging 12 aging 13 of 13 of 14 society 15 in 16 japan we evaluated the utility of our prediction rule modified estimation of physiologic ability and surgical stress ( me - pass ) in predicting postoperative adverse events in patients with choledochocystolithiasis . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 evaluated 0 ###LEFT-WALL### 31 . 1 we 2 evaluated 2 evaluated 4 utility 2 evaluated 22 in 3 the 4 utility 4 utility 5 of 4 utility 11 of 4 utility 20 pass 5 of 10 estimation 6 our 10 estimation 7 prediction 10 estimation 8 rule 9 modified 9 modified 10 estimation 11 of 14 and 12 physiologic 13 ability 13 ability 14 and 14 and 16 stress 14 and 18 me 15 surgical 16 stress 17 ( 18 me 18 me 19 - 19 - 20 pass 20 pass 21 ) 22 in 23 predicting 23 predicting 26 events 23 predicting 27 in 23 predicting 29 with 24 postoperative 26 events 25 adverse 26 events 27 in 28 patients 29 with 30 choledochocystolithiasis methods : a total of 4,329 patients who underwent elective surgery for choledochocystolithiasis in 44 referral hospitals between april 1987 and april 2007 were analyzed for me - pass along with postoperative events . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 34 . 2 : 21 and 2 : 25 analyzed 3 a 4 total 4 total 5 of 4 total 12 for 4 total 21 and 5 of 7 patients 6 4,329 7 patients 7 patients 8 who 7 patients 9 underwent 8 who 9 underwent 9 underwent 11 surgery 10 elective 11 surgery 12 for 13 choledochocystolithiasis 13 choledochocystolithiasis 14 in 13 choledochocystolithiasis 18 between 14 in 17 hospitals 15 44 17 hospitals 16 referral 17 hospitals 18 between 19 april 19 april 20 1987 21 and 22 april 21 and 24 were 22 april 23 2007 24 were 25 analyzed 25 analyzed 26 for 25 analyzed 31 with 26 for 29 pass 27 me 28 - 27 me 29 pass 30 along 31 with 31 with 33 events 32 postoperative 33 events the discrimination power of me - pass was assessed by the area under the receiver operating characteristic curve ( auc ) . 0 ###LEFT-WALL### 3 power 0 ###LEFT-WALL### 9 assessed 0 ###LEFT-WALL### 22 . 1 the 3 power 2 discrimination 3 power 3 power 4 of 3 power 8 was 4 of 7 pass 5 me 6 - 5 me 7 pass 8 was 9 assessed 9 assessed 10 by 9 assessed 13 under 10 by 12 area 11 the 12 area 13 under 18 curve 14 the 18 curve 15 receiver 16 operating 16 operating 18 curve 17 characteristic 18 curve 18 curve 20 auc 19 ( 20 auc 20 auc 21 ) the correlation between ordinal and interval variables was quantified by the spearman rank correlation ( ρ ) . 0 ###LEFT-WALL### 2 correlation 0 ###LEFT-WALL### 9 quantified 0 ###LEFT-WALL### 18 . 1 the 2 correlation 2 correlation 3 between 2 correlation 8 was 3 between 5 and 4 ordinal 5 and 5 and 7 variables 6 interval 7 variables 8 was 9 quantified 9 quantified 10 by 10 by 14 correlation 11 the 14 correlation 12 spearman 14 correlation 13 rank 14 correlation 14 correlation 16 ρ 15 ( 16 ρ 16 ρ 17 ) the ratio [of] observed - to [-] estimated mortality rates ( oe [ratio] ) was used as a metric [of] surgical quality . 0 ###LEFT-WALL### 2 ratio 0 ###LEFT-WALL### 16 used 0 ###LEFT-WALL### 23 . 1 the 2 ratio 2 ratio 4 observed 2 ratio 15 was 4 observed 6 to 5 - 6 to 6 to 10 rates 6 to 14 ) 8 estimated 9 mortality 9 mortality 10 rates 10 rates 12 oe 11 ( 12 oe 12 oe 14 ) 15 was 16 used 16 used 17 as 17 as 22 quality 18 a 19 metric 18 a 22 quality 19 metric 22 quality 21 surgical 22 quality the predicted mortality rates significantly correlated with the severity of postoperative complications ( ρ [=] 0.278 , p < 0.0001 ) and length of hospital stay [(] ρ = 0.479 , p < 0.0001 ) . 0 ###LEFT-WALL### 3 mortality 0 ###LEFT-WALL### 29 = 0 ###LEFT-WALL### 36 . 1 the 3 mortality 2 predicted 3 mortality 3 mortality 4 rates 3 mortality 6 correlated 3 mortality 29 = 4 rates 6 correlated 5 significantly 6 correlated 6 correlated 7 with 7 with 22 and 8 the 9 severity 9 severity 10 of 9 severity 22 and 10 of 12 complications 11 postoperative 12 complications 12 complications 14 ρ 13 ( 14 ρ 14 ρ 19 < 14 ρ 21 ) 16 0.278 19 < 17 , 19 < 18 p 19 < 19 < 20 0.0001 19 < 21 ) 22 and 23 length 22 and 24 of 24 of 28 ρ 25 hospital 28 ρ 26 stay 28 ρ 29 = 30 0.479 30 0.479 33 < 31 , 33 < 32 p 33 < 33 < 34 0.0001 33 < 35 ) the oe ratios ( 95 % ci ) improved slightly over time [;] 1.5 ( 0.25 - 9.0 ) between 1987 and 2000 , [and] 0.40 ( 0.078 - 2.1 ) between 2001 and 2007 . 0 ###LEFT-WALL### 3 ratios 0 ###LEFT-WALL### 9 improved 0 ###LEFT-WALL### 36 . 1 the 3 ratios 2 oe 3 ratios 3 ratios 7 ci 3 ratios 9 improved 4 ( 7 ci 5 95 7 ci 6 % 7 ci 7 ci 8 ) 9 improved 10 slightly 9 improved 11 over 9 improved 14 1.5 9 improved 20 between 9 improved 32 between 11 over 12 time 14 1.5 17 - 15 ( 17 - 16 0.25 17 - 17 - 18 9.0 17 - 19 ) 20 between 22 and 21 1987 22 and 22 and 23 2000 22 and 26 0.40 24 , 26 0.40 26 0.40 29 - 26 0.40 31 ) 27 ( 29 - 28 0.078 29 - 29 - 30 2.1 29 - 31 ) 32 between 34 and 33 2001 34 and 34 and 35 2007 conclusions : the present study suggests that me - pass can predict postoperative risks in patients who have undergone choledochocystolithiasis . me - pass may be useful in surgical decision making and [evaluating] the quality of care . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 5 study 2 : 8 me 2 : 9 - 3 the 5 study 4 present 5 study 5 study 6 suggests 6 suggests 7 that 6 suggests 8 me 9 - 10 pass 9 - 12 predict 9 - 21 . 9 - 26 be 9 - 38 . 10 pass 11 can 11 can 12 predict 12 predict 14 risks 13 postoperative 14 risks 14 risks 15 in 15 in 16 patients 16 patients 17 who 16 patients 18 have 17 who 18 have 18 have 19 undergone 19 undergone 20 choledochocystolithiasis 21 . 24 pass 22 me 23 - 22 me 24 pass 24 pass 25 may 25 may 26 be 26 be 27 useful 27 useful 28 in 28 in 32 and 29 surgical 30 decision 30 decision 31 making 30 decision 32 and 32 and 35 quality 34 the 35 quality 35 quality 36 of 36 of 37 care assessment of cognitive functioning is an important component of telephone surveys of health . 0 ###LEFT-WALL### 1 assessment 0 ###LEFT-WALL### 5 is 0 ###LEFT-WALL### 14 . 1 assessment 2 of 1 assessment 5 is 2 of 4 functioning 3 cognitive 4 functioning 5 is 8 component 6 an 7 important 6 an 8 component 7 important 8 component 8 component 9 of 9 of 11 surveys 10 telephone 11 surveys 11 surveys 12 of 12 of 13 health previous cognitive telephone batteries have been limited in scope with a primary focus on dementia screening . 0 ###LEFT-WALL### 4 batteries 0 ###LEFT-WALL### 6 been 0 ###LEFT-WALL### 17 . 1 previous 3 telephone 2 cognitive 3 telephone 3 telephone 4 batteries 4 batteries 5 have 5 have 6 been 6 been 7 limited 7 limited 8 in 7 limited 10 with 7 limited 14 on 8 in 9 scope 10 with 13 focus 11 a 12 primary 11 a 13 focus 12 primary 13 focus 14 on 16 screening 15 dementia 16 screening the brief test of adult cognition by telephone ( btact ) assesses multiple dimensions central for effective functioning across adulthood : episodic memory , working memory , reasoning , verbal fluency , and executive function . 0 ###LEFT-WALL### 3 test 0 ###LEFT-WALL### 12 assesses 0 ###LEFT-WALL### 21 : 0 ###LEFT-WALL### 36 . 1 the 3 test 2 brief 3 test 3 test 4 of 3 test 7 by 3 test 10 btact 3 test 12 assesses 4 of 6 cognition 5 adult 6 cognition 7 by 8 telephone 9 ( 10 btact 10 btact 11 ) 12 assesses 14 dimensions 12 assesses 19 across 13 multiple 14 dimensions 14 dimensions 15 central 15 central 16 for 16 for 18 functioning 17 effective 18 functioning 19 across 20 adulthood 21 : 23 memory 21 : 27 , 22 episodic 23 memory 23 memory 26 memory 24 , 26 memory 25 working 26 memory 26 memory 27 , 27 , 33 and 28 reasoning 29 , 29 , 31 fluency 29 , 33 and 30 verbal 31 fluency 32 , 33 and 33 and 35 function 34 executive 35 function the btact is the first instrument that includes measures of processing speed , reaction time , and task - switching/inhibitory control for use over the telephone . 0 ###LEFT-WALL### 2 btact 0 ###LEFT-WALL### 3 is 0 ###LEFT-WALL### 19 - 0 ###LEFT-WALL### 20 switching/inhibitory 0 ###LEFT-WALL### 27 . 1 the 2 btact 2 btact 3 is 3 is 6 instrument 4 the 5 first 4 the 6 instrument 6 instrument 7 that 6 instrument 8 includes 6 instrument 17 and 7 that 8 includes 8 includes 9 measures 9 measures 10 of 10 of 11 processing 11 processing 12 speed 13 , 17 and 14 reaction 15 time 15 time 17 and 16 , 17 and 17 and 18 task 17 and 19 - 19 - 20 switching/inhibitory 20 switching/inhibitory 21 control 21 control 22 for 21 control 24 over 22 for 23 use 24 over 26 telephone 25 the 26 telephone we administered the battery to a national sample ( n = 4,268 ) , age 32 to 84 years , from the study of midlife in the united states ( midus ) and examined age , education , and sex differences ; reliability [;] and factor structure . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 administered 0 ###LEFT-WALL### 14 , 0 ###LEFT-WALL### 48 . 1 we 2 administered 2 administered 4 battery 2 administered 5 to 2 administered 11 = 3 the 4 battery 5 to 8 sample 6 a 8 sample 7 national 8 sample 9 ( 11 = 10 n 11 = 11 = 12 4,268 11 = 13 ) 14 , 33 and 14 , 42 ; 15 age 19 years 15 age 21 from 15 age 33 and 16 32 17 to 17 to 18 84 17 to 19 years 20 , 21 from 21 from 23 study 21 from 32 ) 22 the 23 study 23 study 24 of 24 of 25 midlife 25 midlife 26 in 26 in 31 midus 27 the 31 midus 28 united 29 states 29 states 31 midus 30 ( 31 midus 33 and 39 and 34 examined 35 age 34 examined 39 and 35 age 37 education 36 , 37 education 37 education 38 , 39 and 40 sex 40 sex 41 differences 42 ; 45 and 43 reliability 45 and 45 and 47 structure 46 factor 47 structure we found good evidence for construct validity with a subsample tested in person . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 found 0 ###LEFT-WALL### 14 . 1 we 2 found 2 found 4 evidence 2 found 8 with 3 good 4 evidence 4 evidence 5 for 5 for 7 validity 6 construct 7 validity 8 with 10 subsample 9 a 10 subsample 10 subsample 11 tested 11 tested 13 person 12 in 13 person implications of the findings are considered for efficient neuropsychological assessment and monitoring changes in cognitive aging , for clinical and research applications by telephone [or] in person . 0 ###LEFT-WALL### 1 implications 0 ###LEFT-WALL### 6 considered 0 ###LEFT-WALL### 28 . 1 implications 2 of 1 implications 5 are 2 of 4 findings 3 the 4 findings 5 are 6 considered 6 considered 7 for 6 considered 24 telephone 6 considered 27 person 7 for 11 and 8 efficient 10 assessment 9 neuropsychological 10 assessment 10 assessment 11 and 11 and 13 changes 11 and 17 , 11 and 18 for 12 monitoring 13 changes 13 changes 14 in 14 in 16 aging 15 cognitive 16 aging 18 for 20 and 19 clinical 20 and 20 and 22 applications 21 research 22 applications 23 by 24 telephone 26 in 27 person none background/objectives : to explore the effect of ageing on [renal] function with cystatin c as the marker of glomerular filtration [rate] ( gfr ) in the general population without vascular disease or diabetes . 0 ###LEFT-WALL### 1 none 0 ###LEFT-WALL### 12 function 0 ###LEFT-WALL### 35 . 1 none 2 background/objectives 1 none 10 on 1 none 12 function 2 background/objectives 3 : 3 : 4 to 3 : 5 explore 4 to 5 explore 5 explore 7 effect 5 explore 10 on 6 the 7 effect 7 effect 8 of 8 of 9 ageing 12 function 13 with 12 function 16 as 12 function 26 in 13 with 14 cystatin 14 cystatin 15 c 16 as 18 marker 17 the 18 marker 18 marker 19 of 18 marker 24 gfr 19 of 21 filtration 20 glomerular 21 filtration 23 ( 24 gfr 24 gfr 25 ) 26 in 29 population 27 the 29 population 28 general 29 population 29 population 30 without 30 without 33 or 31 vascular 32 disease 32 disease 33 or 33 or 34 diabetes design : a cross - sectional analysis of a healthy subset from the good aging in skåne - cohort study representative of the swedish general population . 0 ###LEFT-WALL### 1 design 0 ###LEFT-WALL### 2 : 1 design 2 : 2 : 4 cross 3 a 4 cross 4 cross 7 analysis 5 - 7 analysis 6 sectional 7 analysis 7 analysis 8 of 7 analysis 12 from 7 analysis 16 in 7 analysis 27 . 8 of 11 subset 9 a 11 subset 10 healthy 11 subset 12 from 15 aging 13 the 15 aging 14 good 15 aging 16 in 17 skåne 17 skåne 21 representative 18 - 21 representative 19 cohort 20 study 20 study 21 representative 21 representative 22 of 21 representative 27 . 22 of 26 population 23 the 26 population 24 swedish 25 general 25 general 26 population subjects : 1252 participants without vascular disease and diabetes ( 43.9 % men ) of whom 203 were over 80 years old were included from the original cohort of 2931 . 0 ###LEFT-WALL### 1 subjects 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 31 . 2 : 4 participants 2 : 24 included 3 1252 4 participants 4 participants 5 without 4 participants 15 of 4 participants 23 were 5 without 8 and 6 vascular 7 disease 7 disease 8 and 8 and 9 diabetes 8 and 13 men 10 ( 13 men 11 43.9 13 men 12 % 13 men 13 men 14 ) 15 of 16 whom 16 whom 17 203 16 whom 18 were 17 203 18 were 18 were 19 over 19 over 20 80 20 80 22 old 21 years 22 old 23 were 24 included 24 included 25 from 25 from 28 cohort 26 the 28 cohort 27 original 28 cohort 28 cohort 29 of 29 of 30 2931 methods : plasma cystatin c and plasma creatinine were used as markers for gfr . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 6 and 2 : 10 used 2 : 15 . 3 plasma 4 cystatin 4 cystatin 5 c 4 cystatin 6 and 6 and 8 creatinine 6 and 9 were 7 plasma 8 creatinine 9 were 10 used 10 used 11 as 11 as 12 markers 12 markers 13 for 13 for 14 gfr estimated gfr ( egfr ) was calculated with three chronic kidney disease epidemiology collaboration ( ckd - epi ) formulas involving cystatin c , creatinine or both . 0 ###LEFT-WALL### 2 gfr 0 ###LEFT-WALL### 7 calculated 1 estimated 2 gfr 2 gfr 4 egfr 2 gfr 6 was 3 ( 4 egfr 4 egfr 5 ) 6 was 7 calculated 7 calculated 8 with 8 with 14 collaboration 9 three 11 kidney 10 chronic 11 kidney 11 kidney 14 collaboration 12 disease 13 epidemiology 13 epidemiology 14 collaboration 14 collaboration 20 formulas 15 ( 20 formulas 16 ckd 18 epi 17 - 18 epi 18 epi 19 ) 18 epi 20 formulas 20 formulas 21 involving 20 formulas 26 or 20 formulas 28 . 21 involving 22 cystatin 22 cystatin 23 c 24 , 26 or 25 creatinine 26 or 26 or 27 both 26 or 28 . results : the median for plasma cystatin c was 0.93 mg/l [(] 60 - 69 years old [ )(, 1.04 ( 70 - 79 years old ) and 1.24 [(] 80+ years old ) . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 35 . 1 results 2 : 2 : 28 and 3 the 4 median 4 median 5 for 4 median 28 and 5 for 6 plasma 6 plasma 17 old 6 plasma 20 1.04 7 cystatin 8 c 7 cystatin 9 was 9 was 14 - 10 0.93 11 mg/l 10 0.93 14 - 11 mg/l 13 60 14 - 15 69 15 69 16 years 16 years 17 old 19 )(, 20 1.04 20 1.04 22 70 20 1.04 26 old 20 1.04 27 ) 21 ( 22 70 22 70 23 - 23 - 26 old 24 79 25 years 25 years 26 old 26 old 27 ) 28 and 31 80+ 28 and 34 ) 29 1.24 31 80+ 31 80+ 33 old 32 years 33 old the difference in [mg/l] [between] the 5th and 95th percentile was 0.46 , 0.62 and 0.90 for these age groups . 0 ###LEFT-WALL### 2 difference 0 ###LEFT-WALL### 11 was 1 the 2 difference 2 difference 3 in 2 difference 11 was 3 in 10 percentile 6 the 7 5th 7 5th 8 and 8 and 9 95th 8 and 10 percentile 11 was 12 0.46 12 0.46 15 and 13 , 15 and 14 0.62 15 and 15 and 16 0.90 15 and 17 for 15 and 21 . 17 for 20 groups 18 these 20 groups 19 age 20 groups male sex increased the age effect on plasma cystatin c levels with 0.004 mg/l/year ( p = 0.03 ) , adjusted for vascular risk factors . 0 ###LEFT-WALL### 2 sex 0 ###LEFT-WALL### 20 , 0 ###LEFT-WALL### 26 . 1 male 2 sex 2 sex 20 , 3 increased 6 effect 3 increased 7 on 3 increased 12 with 3 increased 17 = 3 increased 20 , 4 the 6 effect 5 age 6 effect 7 on 11 levels 8 plasma 11 levels 9 cystatin 10 c 9 cystatin 11 levels 12 with 14 mg/l/year 13 0.004 14 mg/l/year 15 ( 17 = 16 p 17 = 17 = 18 0.03 17 = 19 ) 20 , 21 adjusted 20 , 22 for 22 for 25 factors 23 vascular 25 factors 24 risk 25 factors smoking , lower hdl and higher diastolic blood pressure were associated with higher cystatin c levels . 0 ###LEFT-WALL### 5 and 0 ###LEFT-WALL### 11 associated 0 ###LEFT-WALL### 17 . 1 smoking 2 , 1 smoking 5 and 3 lower 4 hdl 4 hdl 5 and 5 and 9 pressure 5 and 10 were 6 higher 8 blood 7 diastolic 8 blood 8 blood 9 pressure 10 were 11 associated 11 associated 12 with 12 with 16 levels 13 higher 14 cystatin 14 cystatin 15 c 14 cystatin 16 levels conclusion : [non] - diabetics without overt vascular disease exhibit an age related [but] heterogeneous decline [in] renal function . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 4 - 2 : 10 exhibit 2 : 20 . 4 - 5 diabetics 5 diabetics 6 without 5 diabetics 10 exhibit 6 without 9 disease 7 overt 9 disease 8 vascular 9 disease 10 exhibit 19 function 11 an 12 age 11 an 19 function 12 age 13 related 13 related 16 decline 15 heterogeneous 16 decline 16 decline 19 function 18 renal 19 function the ageing effect is more pronounced in men . 0 ###LEFT-WALL### 3 effect 0 ###LEFT-WALL### 6 pronounced 0 ###LEFT-WALL### 9 . 1 the 3 effect 2 ageing 3 effect 3 effect 4 is 4 is 5 more 4 is 6 pronounced 6 pronounced 7 in 7 in 8 men at least half of healthy 80+ years old could be expected to have at least ckd stage 3 with egfr < 60 ml/min/1.73 m2 . 0 ###LEFT-WALL### 10 be 0 ###LEFT-WALL### 25 . 1 at 2 least 2 least 3 half 3 half 4 of 3 half 9 could 4 of 6 80+ 5 healthy 6 80+ 6 80+ 8 old 7 years 8 old 9 could 10 be 10 be 11 expected 11 expected 12 to 12 to 13 have 13 have 15 least 13 have 17 stage 13 have 19 with 14 at 15 least 16 ckd 17 stage 17 stage 18 3 19 with 20 egfr 19 with 24 m2 20 egfr 22 60 20 egfr 23 ml/min/1.73 21 < 22 60 22 60 23 ml/min/1.73 background : structure and function of the human brain are subjected to dramatic changes during its development and aging . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 4 and 2 : 11 subjected 2 : 20 . 3 structure 4 and 4 and 5 function 4 and 6 of 4 and 10 are 6 of 9 brain 7 the 9 brain 8 human 9 brain 10 are 11 subjected 11 subjected 12 to 11 subjected 15 during 12 to 14 changes 13 dramatic 14 changes 15 during 18 and 16 its 17 development 17 development 18 and 18 and 19 aging studies have demonstrated that micrornas ( mirnas ) play an important role in the regulation of brain development and have a significant impact on brain aging and neurodegeneration . 0 ###LEFT-WALL### 1 studies 0 ###LEFT-WALL### 20 have 0 ###LEFT-WALL### 29 . 1 studies 2 have 2 have 3 demonstrated 3 demonstrated 4 that 4 that 5 micrornas 4 that 19 and 5 micrornas 7 mirnas 5 micrornas 19 and 6 ( 7 mirnas 7 mirnas 8 ) 9 play 12 role 9 play 13 in 9 play 19 and 10 an 11 important 10 an 12 role 11 important 12 role 13 in 15 regulation 14 the 15 regulation 15 regulation 16 of 16 of 18 development 17 brain 18 development 19 and 20 have 20 have 23 impact 20 have 24 on 21 a 23 impact 22 significant 23 impact 24 on 27 and 25 brain 26 aging 25 brain 27 and 27 and 28 neurodegeneration however , the underlining molecular mechanisms are not well understood . 0 ###LEFT-WALL### 4 underlining 0 ###LEFT-WALL### 10 understood 0 ###LEFT-WALL### 11 . 1 however 2 , 1 however 4 underlining 3 the 4 underlining 4 underlining 6 mechanisms 4 underlining 9 well 4 underlining 10 understood 5 molecular 6 mechanisms 6 mechanisms 7 are 7 are 8 not 7 are 9 well in general , development and aging are conventionally studied separately , which may not completely address the physiological mechanism over the entire lifespan . 0 ###LEFT-WALL### 5 and 0 ###LEFT-WALL### 9 studied 0 ###LEFT-WALL### 11 , 0 ###LEFT-WALL### 24 . 1 in 2 general 2 general 3 , 2 general 5 and 4 development 5 and 5 and 6 aging 5 and 7 are 7 are 9 studied 8 conventionally 9 studied 9 studied 10 separately 11 , 12 which 11 , 16 address 12 which 13 may 13 may 14 not 13 may 16 address 15 completely 16 address 16 address 19 mechanism 16 address 20 over 17 the 19 mechanism 18 physiological 19 mechanism 20 over 23 lifespan 21 the 23 lifespan 22 entire 23 lifespan thus , we study the regulatory effect between mirnas and mrnas in the developmental and aging process of the human brain by integrating mirna and mrna expression profiles throughout the lifetime . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 15 and 0 ###LEFT-WALL### 32 . 1 thus 2 , 1 thus 3 we 3 we 10 and 4 study 7 effect 4 study 8 between 4 study 10 and 5 the 7 effect 6 regulatory 7 effect 8 between 9 mirnas 10 and 11 mrnas 10 and 12 in 12 in 14 developmental 13 the 14 developmental 15 and 17 process 15 and 28 profiles 16 aging 17 process 17 process 18 of 17 process 28 profiles 18 of 25 and 19 the 21 brain 20 human 21 brain 21 brain 22 by 21 brain 25 and 22 by 23 integrating 23 integrating 24 mirna 25 and 27 expression 26 mrna 27 expression 28 profiles 29 throughout 28 profiles 31 lifetime 30 the 31 lifetime methods : in this study , we integrated mirna and mrna expression profiles in the human brain across lifespan from the network perspective . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 7 we 2 : 8 integrated 2 : 24 . 3 in 5 study 3 in 6 , 3 in 7 we 4 this 5 study 7 we 8 integrated 8 integrated 13 profiles 8 integrated 20 from 9 mirna 10 and 10 and 11 mrna 10 and 13 profiles 12 expression 13 profiles 13 profiles 14 in 14 in 17 brain 15 the 17 brain 16 human 17 brain 17 brain 18 across 18 across 19 lifespan 20 from 23 perspective 21 the 23 perspective 22 network 23 perspective first , we chose the age - related mirnas by polynomial regression models . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 chose 0 ###LEFT-WALL### 8 related 1 first 2 , 1 first 3 we 3 we 4 chose 4 chose 6 age 5 the 6 age 7 - 8 related 8 related 9 mirnas 8 related 10 by 8 related 14 . 10 by 13 models 11 polynomial 12 regression 12 regression 13 models second , we constructed the bipartite mirna - mrna regulatory network by pair [-] wise correlation coefficient analysis between mirna and mrna expression profiles . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 constructed 0 ###LEFT-WALL### 25 . 1 second 2 , 1 second 3 we 3 we 4 constructed 4 constructed 11 network 4 constructed 19 between 5 the 11 network 6 bipartite 11 network 7 mirna 8 - 7 mirna 11 network 9 mrna 11 network 10 regulatory 11 network 11 network 12 by 12 by 18 analysis 13 pair 18 analysis 15 wise 16 correlation 16 correlation 18 analysis 17 coefficient 18 analysis 19 between 21 and 20 mirna 21 and 21 and 22 mrna 21 and 23 expression 21 and 24 profiles 23 expression 24 profiles at last , we constructed the mirna - mirna synergistic network from the mirna - mrna network , considering not only the enrichment of target genes but also go function enrichment of co - regulated target genes . 0 ###LEFT-WALL### 4 we 0 ###LEFT-WALL### 5 constructed 0 ###LEFT-WALL### 34 - 1 at 2 last 1 at 3 , 1 at 4 we 4 we 5 constructed 5 constructed 11 network 6 the 11 network 7 mirna 8 - 7 mirna 11 network 9 mirna 11 network 10 synergistic 11 network 11 network 12 from 12 from 17 network 13 the 17 network 14 mirna 15 - 14 mirna 17 network 16 mrna 17 network 17 network 19 considering 18 , 19 considering 19 considering 28 also 19 considering 31 enrichment 19 considering 34 - 20 not 21 only 21 only 28 also 22 the 23 enrichment 23 enrichment 24 of 23 enrichment 28 also 24 of 26 genes 25 target 26 genes 27 but 28 also 28 also 29 go 30 function 31 enrichment 31 enrichment 32 of 32 of 33 co 34 - 37 genes 34 - 38 . 35 regulated 36 target 36 target 37 genes results : we found that the average degree of age - related mirnas was significantly higher than that of [non] age - related mirnas in the mirna - mrna regulatory network . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 3 we 2 : 4 found 2 : 23 related 2 : 32 . 3 we 4 found 4 found 5 that 5 that 10 age 5 that 14 was 6 the 8 degree 7 average 8 degree 8 degree 9 of 8 degree 10 age 9 of 10 age 10 age 14 was 11 - 12 related 12 related 13 mirnas 12 related 14 was 14 was 16 higher 14 was 17 than 15 significantly 16 higher 17 than 18 that 17 than 19 of 19 of 21 age 22 - 23 related 23 related 24 mirnas 23 related 25 in 25 in 31 network 26 the 31 network 27 mirna 28 - 27 mirna 31 network 29 mrna 31 network 30 regulatory 31 network the topological features between age - [related] and [non] age - related mirnas were significantly different , and 34 reliable age - related mirna synergistic modules were identified using cfinder in the mirna - mirna synergistic network . 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 14 were 0 ###LEFT-WALL### 38 . 1 the 3 features 2 topological 3 features 3 features 4 between 3 features 8 and 4 between 5 age 6 - 8 and 8 and 10 age 8 and 14 were 11 - 12 related 12 related 13 mirnas 12 related 14 were 14 were 30 cfinder 14 were 31 in 15 significantly 16 different 16 different 18 and 17 , 18 and 18 and 29 using 18 and 30 cfinder 19 34 21 age 20 reliable 21 age 21 age 29 using 22 - 23 related 23 related 24 mirna 23 related 28 identified 24 mirna 26 modules 24 mirna 27 were 25 synergistic 26 modules 26 modules 27 were 28 identified 29 using 31 in 37 network 32 the 37 network 33 mirna 34 - 33 mirna 35 mirna 35 mirna 37 network 36 synergistic 37 network the synergistic regulations of module genes were verified by reviewing mirna target databases and previous studies . 0 ###LEFT-WALL### 3 regulations 0 ###LEFT-WALL### 8 verified 0 ###LEFT-WALL### 17 . 1 the 3 regulations 2 synergistic 3 regulations 3 regulations 4 of 3 regulations 7 were 4 of 6 genes 5 module 6 genes 7 were 8 verified 8 verified 9 by 9 by 10 reviewing 10 reviewing 14 and 11 mirna 13 databases 12 target 13 databases 13 databases 14 and 14 and 16 studies 15 previous 16 studies conclusions : age - related mirnas play a more important role than [non] age - related mrrnas in the developmental and aging process of the human brain . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 3 age 0 ###LEFT-WALL### 4 - 1 conclusions 2 : 2 : 3 age 4 - 6 mirnas 4 - 7 play 4 - 16 related 4 - 28 . 5 related 6 mirnas 6 mirnas 7 play 7 play 11 role 7 play 12 than 8 a 11 role 9 more 10 important 10 important 11 role 12 than 14 age 15 - 16 related 16 related 21 and 17 mrrnas 18 in 17 mrrnas 21 and 18 in 20 developmental 19 the 20 developmental 21 and 23 process 21 and 24 of 22 aging 23 process 24 of 27 brain 25 the 27 brain 26 human 27 brain the age - related mirnas have synergism , which tend to work together as small modules . 0 ###LEFT-WALL### 2 age 0 ###LEFT-WALL### 3 - 1 the 2 age 3 - 5 mirnas 3 - 6 have 3 - 8 , 3 - 17 . 4 related 5 mirnas 5 mirnas 6 have 6 have 7 synergism 8 , 9 which 8 , 10 tend 9 which 10 tend 10 tend 11 to 10 tend 12 work 11 to 12 work 12 work 13 together 12 work 14 as 14 as 16 modules 15 small 16 modules these results may provide a new insight into the regulation of mirnas in the developmental and aging process of the human brain . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 4 provide 0 ###LEFT-WALL### 23 . 1 these 2 results 2 results 3 may 3 may 4 provide 4 provide 7 insight 4 provide 8 into 4 provide 13 in 5 a 6 new 5 a 7 insight 6 new 7 insight 8 into 10 regulation 9 the 10 regulation 10 regulation 11 of 11 of 12 mirnas 13 in 16 and 14 the 15 developmental 15 developmental 16 and 16 and 18 process 16 and 19 of 17 aging 18 process 19 of 22 brain 20 the 22 brain 21 human 22 brain identifying the goal of another agent 's action allows an observer to make inferences not only about the outcomes the agent will pursue in the future and the means to be deployed in a given context , but also about the emotional consequences of goal [-] related outcomes . 0 ###LEFT-WALL### 1 identifying 0 ###LEFT-WALL### 9 allows 0 ###LEFT-WALL### 15 not 0 ###LEFT-WALL### 49 . 1 identifying 3 goal 1 identifying 9 allows 2 the 3 goal 3 goal 4 of 4 of 8 action 5 another 6 agent 6 agent 7 's 7 's 8 action 9 allows 11 observer 9 allows 12 to 9 allows 13 make 10 an 11 observer 12 to 13 make 13 make 14 inferences 15 not 16 only 15 not 21 agent 15 not 23 pursue 17 about 19 outcomes 17 about 21 agent 18 the 19 outcomes 20 the 21 agent 21 agent 22 will 22 will 23 pursue 23 pursue 24 in 23 pursue 30 to 23 pursue 43 consequences 24 in 27 and 25 the 26 future 26 future 27 and 27 and 29 means 28 the 29 means 30 to 31 be 31 be 32 deployed 32 deployed 38 but 33 in 36 context 33 in 38 but 34 a 36 context 35 given 36 context 37 , 38 but 38 but 39 also 38 but 40 about 40 about 42 emotional 41 the 42 emotional 43 consequences 44 of 44 of 48 outcomes 45 goal 47 related 47 related 48 outcomes while numerous studies have characterized the former abilities in infancy , expectations about emotions have gone relatively unexplored . 0 ###LEFT-WALL### 12 expectations 0 ###LEFT-WALL### 16 gone 0 ###LEFT-WALL### 19 . 1 while 3 studies 1 while 5 characterized 1 while 11 , 1 while 12 expectations 2 numerous 3 studies 3 studies 4 have 4 have 5 characterized 5 characterized 8 abilities 5 characterized 9 in 6 the 8 abilities 7 former 8 abilities 9 in 10 infancy 12 expectations 13 about 12 expectations 15 have 13 about 14 emotions 15 have 16 gone 16 gone 18 unexplored 17 relatively 18 unexplored using a violation of expectation [paradigm] , we present infants with an agent who [attains] [or] fails to attain a demonstrated goal , and reacts with positive or negative [affect] . 0 ###LEFT-WALL### 8 we 0 ###LEFT-WALL### 9 present 0 ###LEFT-WALL### 31 . 1 using 3 violation 1 using 7 , 1 using 8 we 2 a 3 violation 3 violation 4 of 4 of 5 expectation 8 we 9 present 9 present 10 infants 9 present 11 with 9 present 26 with 11 with 13 agent 12 an 13 agent 13 agent 14 who 13 agent 24 and 14 who 24 and 17 fails 18 to 17 fails 19 attain 17 fails 24 and 18 to 19 attain 19 attain 22 goal 20 a 22 goal 21 demonstrated 22 goal 23 , 24 and 24 and 25 reacts 26 with 28 or 27 positive 28 or 28 or 29 negative across several studies , we find that infants ' attention to a given emotional display differs [depending] on whether that reaction is congruent with the preceding goal outcome . 0 ###LEFT-WALL### 5 we 0 ###LEFT-WALL### 6 find 0 ###LEFT-WALL### 29 . 1 across 3 studies 1 across 4 , 1 across 5 we 2 several 3 studies 5 we 6 find 6 find 7 that 7 that 10 attention 7 that 16 differs 8 infants 9 ' 9 ' 10 attention 10 attention 11 to 10 attention 16 differs 11 to 15 display 12 a 15 display 13 given 15 display 14 emotional 15 display 16 differs 18 on 18 on 19 whether 19 whether 21 reaction 19 whether 22 is 20 that 21 reaction 21 reaction 22 is 22 is 23 congruent 23 congruent 24 with 24 with 28 outcome 25 the 28 outcome 26 preceding 28 outcome 27 goal 28 outcome specifically , infants look longer at a negative emotional display when it follows a completed goal compared to when it follows a failed goal . 0 ###LEFT-WALL### 3 infants 0 ###LEFT-WALL### 4 look 0 ###LEFT-WALL### 25 . 1 specifically 2 , 1 specifically 3 infants 3 infants 4 look 4 look 5 longer 4 look 6 at 4 look 19 when 6 at 10 display 7 a 8 negative 7 a 10 display 8 negative 10 display 9 emotional 10 display 10 display 11 when 10 display 16 goal 10 display 18 to 11 when 12 it 11 when 13 follows 12 it 13 follows 14 a 16 goal 15 completed 16 goal 16 goal 17 compared 17 compared 18 to 19 when 20 it 19 when 21 follows 20 it 21 follows 21 follows 24 goal 22 a 24 goal 23 failed 24 goal the present results suggest that infants ' goal representations support expectations not only about future actions but also about emotional reactions , and that infants in the first year of life can relate different emotional reactions to conditions that elicit them . 0 ###LEFT-WALL### 3 results 0 ###LEFT-WALL### 4 suggest 0 ###LEFT-WALL### 12 not 0 ###LEFT-WALL### 42 . 1 the 3 results 2 present 3 results 3 results 4 suggest 4 suggest 5 that 5 that 9 representations 5 that 10 support 6 infants 7 ' 7 ' 9 representations 8 goal 9 representations 9 representations 10 support 10 support 11 expectations 12 not 13 only 12 not 25 infants 12 not 33 relate 14 about 16 actions 14 about 25 infants 15 future 16 actions 16 actions 17 but 16 actions 19 about 17 but 18 also 19 about 23 and 20 emotional 21 reactions 21 reactions 23 and 22 , 23 and 23 and 24 that 25 infants 26 in 25 infants 32 can 26 in 29 year 27 the 29 year 28 first 29 year 29 year 30 of 30 of 31 life 32 can 33 relate 33 relate 36 reactions 33 relate 37 to 34 different 36 reactions 35 emotional 36 reactions 37 to 38 conditions 38 conditions 39 that 38 conditions 40 elicit 39 that 40 elicit 40 elicit 41 them human memory is a highly heritable polygenic trait with complex inheritance patterns . 0 ###LEFT-WALL### 2 memory 0 ###LEFT-WALL### 3 is 0 ###LEFT-WALL### 13 . 1 human 2 memory 2 memory 3 is 3 is 8 trait 4 a 5 highly 4 a 8 trait 5 highly 6 heritable 6 heritable 8 trait 7 polygenic 8 trait 8 trait 9 with 9 with 12 patterns 10 complex 11 inheritance 11 inheritance 12 patterns to study the genetics of memory and memory - related diseases , hippocampal functioning has served as an intermediate phenotype . 0 ###LEFT-WALL### 1 to 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 10 related 0 ###LEFT-WALL### 12 , 0 ###LEFT-WALL### 21 . 1 to 2 study 2 study 4 genetics 3 the 4 genetics 4 genetics 5 of 5 of 7 and 6 memory 7 and 7 and 8 memory 9 - 10 related 10 related 11 diseases 10 related 12 , 12 , 14 functioning 12 , 16 served 13 hippocampal 14 functioning 14 functioning 15 has 15 has 16 served 16 served 17 as 17 as 20 phenotype 18 an 19 intermediate 18 an 20 phenotype 19 intermediate 20 phenotype the importance of investigating gene [-] gene effects [on] complex [phenotypes] has been emphasized , but most imaging studies still focus on single polymorphisms . 0 ###LEFT-WALL### 2 importance 0 ###LEFT-WALL### 14 emphasized 0 ###LEFT-WALL### 16 but 0 ###LEFT-WALL### 25 . 1 the 2 importance 2 importance 3 of 2 importance 8 effects 2 importance 10 complex 2 importance 12 has 3 of 4 investigating 5 gene 7 gene 7 gene 8 effects 8 effects 10 complex 12 has 13 been 13 been 14 emphasized 15 , 16 but 16 but 18 imaging 16 but 19 studies 17 most 18 imaging 18 imaging 19 studies 19 studies 21 focus 19 studies 22 on 20 still 21 focus 22 on 24 polymorphisms 23 single 24 polymorphisms apoe ε4 and bdnf met , two of the most studied gene variants for variability in memory performance and neuropsychiatric disorders , have both separately been related to poorer episodic memory and altered hippocampal functioning . 0 ###LEFT-WALL### 1 apoe 0 ###LEFT-WALL### 2 ε4 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 36 . 1 apoe 2 ε4 3 and 5 met 3 and 32 and 4 bdnf 5 met 5 met 7 two 5 met 32 and 6 , 7 two 7 two 8 of 7 two 22 , 8 of 19 and 9 the 13 variants 10 most 11 studied 11 studied 12 gene 12 gene 13 variants 13 variants 14 for 13 variants 19 and 14 for 15 variability 15 variability 16 in 16 in 18 performance 17 memory 18 performance 19 and 21 disorders 20 neuropsychiatric 21 disorders 23 have 26 been 23 have 32 and 24 both 26 been 25 separately 26 been 26 been 27 related 27 related 28 to 28 to 31 memory 29 poorer 31 memory 30 episodic 31 memory 32 and 33 altered 33 altered 35 functioning 34 hippocampal 35 functioning here , we investigated the combined effect of apoe and bdnf on hippocampal activation ( n=151 ) . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 investigated 0 ###LEFT-WALL### 18 . 1 here 2 , 1 here 3 we 3 we 4 investigated 4 investigated 7 effect 4 investigated 12 on 5 the 7 effect 6 combined 7 effect 7 effect 8 of 8 of 11 bdnf 9 apoe 10 and 10 and 11 bdnf 12 on 14 activation 13 hippocampal 14 activation 14 activation 16 n=151 15 ( 16 n=151 16 n=151 17 ) no [non] - additive interaction effects were seen . 0 ###LEFT-WALL### 6 effects 0 ###LEFT-WALL### 8 seen 0 ###LEFT-WALL### 9 . 1 no 3 - 1 no 6 effects 4 additive 6 effects 5 interaction 6 effects 6 effects 7 were 7 were 8 seen instead , the results revealed decreased activation in bilateral hippocampus and parahippocampus as a function of the number of apoe ε4 and bdnf met alleles present ( neither , one , or both ) . 0 ###LEFT-WALL### 4 results 0 ###LEFT-WALL### 5 revealed 0 ###LEFT-WALL### 35 . 1 instead 2 , 1 instead 4 results 3 the 4 results 4 results 5 revealed 5 revealed 7 activation 5 revealed 8 in 5 revealed 13 as 6 decreased 7 activation 8 in 11 and 9 bilateral 10 hippocampus 10 hippocampus 11 and 11 and 12 parahippocampus 13 as 22 and 14 a 15 function 15 function 16 of 15 function 19 of 15 function 22 and 16 of 18 number 17 the 18 number 19 of 21 ε4 20 apoe 21 ε4 22 and 23 bdnf 22 and 25 alleles 22 and 26 present 22 and 28 neither 22 and 32 or 24 met 25 alleles 25 alleles 26 present 27 ( 28 neither 28 neither 29 , 29 , 32 or 30 one 32 or 31 , 32 or 32 or 33 both 32 or 34 ) the combined effect was stronger than either of the individual effects , and both gene variables explained significant proportions of variance in bold signal change . 0 ###LEFT-WALL### 3 effect 0 ###LEFT-WALL### 4 was 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 26 . 1 the 3 effect 2 combined 3 effect 3 effect 4 was 4 was 5 stronger 5 stronger 6 than 6 than 7 either 7 either 8 of 8 of 11 effects 9 the 11 effects 10 individual 11 effects 12 , 13 and 13 and 16 variables 13 and 17 explained 14 both 16 variables 15 gene 16 variables 16 variables 17 explained 17 explained 19 proportions 17 explained 24 signal 18 significant 19 proportions 19 proportions 20 of 19 proportions 22 in 19 proportions 24 signal 20 of 21 variance 22 in 23 bold 24 signal 25 change thus , there was an additive gene - gene effect of apoe and bdnf on medial temporal [lobe] ( mtl ) activation , showing that a larger proportion of variance in brain activation attributed to genetics can be explained by considering more than one gene variant . 0 ###LEFT-WALL### 3 there 0 ###LEFT-WALL### 4 was 0 ###LEFT-WALL### 39 explained 1 thus 2 , 1 thus 3 there 3 there 4 was 4 was 7 gene 5 an 7 gene 6 additive 7 gene 7 gene 13 and 8 - 13 and 9 gene 10 effect 10 effect 11 of 10 effect 13 and 11 of 12 apoe 13 and 14 bdnf 13 and 23 , 14 bdnf 15 on 15 on 22 activation 16 medial 22 activation 17 temporal 20 mtl 17 temporal 21 ) 17 temporal 22 activation 19 ( 20 mtl 20 mtl 21 ) 24 showing 25 that 24 showing 39 explained 25 that 28 proportion 25 that 38 be 26 a 28 proportion 27 larger 28 proportion 28 proportion 29 of 28 proportion 37 can 29 of 30 variance 30 variance 31 in 31 in 33 activation 32 brain 33 activation 33 activation 34 attributed 34 attributed 35 to 35 to 36 genetics 37 can 38 be 39 explained 40 by 39 explained 43 than 39 explained 47 . 40 by 41 considering 41 considering 42 more 43 than 46 variant 44 one 46 variant 45 gene 46 variant this effect might be relevant for the understanding of normal variability in memory [function] as well as memory - related disorders associated with apoe and bdnf . 0 ###LEFT-WALL### 2 effect 0 ###LEFT-WALL### 4 be 0 ###LEFT-WALL### 20 related 0 ###LEFT-WALL### 27 . 1 this 2 effect 2 effect 3 might 3 might 4 be 4 be 5 relevant 5 relevant 6 for 5 relevant 12 in 6 for 8 understanding 7 the 8 understanding 8 understanding 9 of 9 of 11 variability 10 normal 11 variability 12 in 13 memory 13 memory 17 as 15 as 16 well 16 well 17 as 17 as 18 memory 19 - 20 related 20 related 21 disorders 20 related 23 with 21 disorders 22 associated 23 with 26 bdnf 24 apoe 25 and 25 and 26 bdnf age related [increase] in body fat mass [,] visceral adipose tissue ( at ) , and ectopic fat deposition are strongly related to worse health conditions in the elderly . 0 ###LEFT-WALL### 16 and 0 ###LEFT-WALL### 22 related 0 ###LEFT-WALL### 30 . 1 age 2 related 1 age 16 and 2 related 4 in 4 in 11 tissue 5 body 7 mass 6 fat 7 mass 7 mass 11 tissue 9 visceral 10 adipose 10 adipose 11 tissue 11 tissue 13 at 12 ( 13 at 13 at 14 ) 15 , 16 and 16 and 19 deposition 16 and 20 are 17 ectopic 19 deposition 18 fat 19 deposition 20 are 21 strongly 20 are 22 related 22 related 23 to 22 related 27 in 23 to 26 conditions 24 worse 25 health 25 health 26 conditions 27 in 29 elderly 28 the 29 elderly moreover , with aging higher inflammation in adipose tissue may be observed and may contribute to inflammaging . 0 ###LEFT-WALL### 9 tissue 0 ###LEFT-WALL### 11 be 0 ###LEFT-WALL### 18 . 1 moreover 2 , 1 moreover 9 tissue 3 with 4 aging 3 with 9 tissue 4 aging 6 inflammation 4 aging 7 in 5 higher 6 inflammation 7 in 8 adipose 9 tissue 10 may 10 may 11 be 11 be 13 and 12 observed 13 and 13 and 14 may 14 may 15 contribute 15 contribute 16 to 16 to 17 inflammaging aging may significantly affect at [function] by modifying the profile of adipokines produced by adipose cells , reducing preadipocytes number and their function and increasing at macrophages infiltration . 0 ###LEFT-WALL### 1 aging 0 ###LEFT-WALL### 4 affect 0 ###LEFT-WALL### 24 and 0 ###LEFT-WALL### 29 . 1 aging 2 may 2 may 4 affect 3 significantly 4 affect 4 affect 5 at 4 affect 7 by 7 by 8 modifying 8 modifying 21 and 9 the 10 profile 10 profile 11 of 10 profile 17 , 11 of 12 adipokines 12 adipokines 13 produced 12 adipokines 14 by 14 by 16 cells 15 adipose 16 cells 17 , 20 number 17 , 21 and 18 reducing 20 number 19 preadipocytes 20 number 21 and 23 function 22 their 23 function 24 and 25 increasing 24 and 27 macrophages 25 increasing 26 at 25 increasing 27 macrophages 27 macrophages 28 infiltration the initiating events of the inflammatory cascade promoting a greater [at] inflammatory profile are not completely understood . 0 ###LEFT-WALL### 3 events 0 ###LEFT-WALL### 14 are 0 ###LEFT-WALL### 18 . 1 the 3 events 2 initiating 3 events 3 events 4 of 3 events 8 promoting 3 events 14 are 4 of 7 cascade 5 the 7 cascade 6 inflammatory 7 cascade 8 promoting 13 profile 9 a 13 profile 10 greater 13 profile 12 inflammatory 13 profile 14 are 15 not 14 are 17 understood 15 not 17 understood 16 completely 17 understood nutrients may determine changes in the amount of body fat , in its distribution as well as in at function with some nutrients showing a pro - inflammatory effect on at . 0 ###LEFT-WALL### 1 nutrients 0 ###LEFT-WALL### 3 determine 0 ###LEFT-WALL### 11 , 0 ###LEFT-WALL### 32 . 1 nutrients 2 may 2 may 3 determine 3 determine 4 changes 3 determine 5 in 5 in 7 amount 6 the 7 amount 7 amount 8 of 8 of 10 fat 9 body 10 fat 11 , 20 function 11 , 27 - 12 in 14 distribution 12 in 20 function 13 its 14 distribution 14 distribution 15 as 15 as 16 well 16 well 17 as 17 as 18 in 18 in 19 at 20 function 21 with 21 with 23 nutrients 22 some 23 nutrients 23 nutrients 24 showing 24 showing 26 pro 25 a 26 pro 27 - 29 effect 28 inflammatory 29 effect 29 effect 30 on 30 on 31 at [evidences] are sparse and quite controversial with only a few studies performed in older subjects . 0 ###LEFT-WALL### 2 are 0 ###LEFT-WALL### 16 . 2 are 11 studies 3 sparse 4 and 4 and 6 controversial 4 and 11 studies 5 quite 6 controversial 6 controversial 7 with 7 with 10 few 8 only 10 few 9 a 10 few 11 studies 12 performed 12 performed 13 in 13 in 15 subjects 14 older 15 subjects different dietary patterns are the result of the complex interaction of foods and nutrients , thus more studies are needed to evaluate the association between dietary patterns and changes in adipose tissue structure , distribution and function in the elderly . 0 ###LEFT-WALL### 3 patterns 0 ###LEFT-WALL### 4 are 0 ###LEFT-WALL### 15 , 0 ###LEFT-WALL### 41 . 1 different 3 patterns 2 dietary 3 patterns 3 patterns 4 are 4 are 13 and 5 the 6 result 6 result 7 of 6 result 11 of 6 result 13 and 7 of 10 interaction 8 the 10 interaction 9 complex 10 interaction 11 of 12 foods 13 and 14 nutrients 15 , 18 studies 15 , 28 and 16 thus 18 studies 17 more 18 studies 18 studies 19 are 19 are 28 and 20 needed 21 to 20 needed 22 evaluate 20 needed 28 and 21 to 22 evaluate 22 evaluate 24 association 22 evaluate 25 between 23 the 24 association 25 between 27 patterns 26 dietary 27 patterns 28 and 29 changes 28 and 30 in 30 in 36 and 31 adipose 33 structure 32 tissue 33 structure 33 structure 34 , 34 , 35 distribution 34 , 36 and 36 and 37 function 36 and 38 in 38 in 40 elderly 39 the 40 elderly a number of oxidative protein modifications have been well characterized during the past decade . 0 ###LEFT-WALL### 6 modifications 0 ###LEFT-WALL### 8 been 0 ###LEFT-WALL### 15 . 1 a 2 number 2 number 3 of 2 number 6 modifications 3 of 6 modifications 4 oxidative 5 protein 5 protein 6 modifications 6 modifications 7 have 7 have 8 been 8 been 9 well 9 well 10 characterized 10 characterized 11 during 11 during 14 decade 12 the 14 decade 13 past 14 decade presumably , reversible oxidative posttranslational modifications ( ptms ) play a significant role in redox signaling pathways , whereas irreversible modifications including reactive protein carbonyl groups are harmful , [as] their levels are typically increased during aging and in certain diseases . 0 ###LEFT-WALL### 6 modifications 0 ###LEFT-WALL### 10 play 0 ###LEFT-WALL### 29 , 0 ###LEFT-WALL### 42 . 1 presumably 2 , 1 presumably 6 modifications 3 reversible 6 modifications 4 oxidative 6 modifications 5 posttranslational 6 modifications 6 modifications 8 ptms 6 modifications 10 play 7 ( 8 ptms 8 ptms 9 ) 10 play 13 role 10 play 14 in 10 play 19 whereas 11 a 12 significant 11 a 13 role 12 significant 13 role 14 in 15 redox 15 redox 16 signaling 16 signaling 17 pathways 18 , 19 whereas 19 whereas 21 modifications 19 whereas 27 are 19 whereas 29 , 20 irreversible 21 modifications 21 modifications 22 including 21 modifications 27 are 22 including 26 groups 23 reactive 24 protein 24 protein 26 groups 25 carbonyl 26 groups 27 are 28 harmful 29 , 32 levels 29 , 33 are 31 their 32 levels 32 levels 33 are 33 are 34 typically 33 are 38 and 34 typically 35 increased 36 during 37 aging 36 during 38 and 38 and 39 in 39 in 41 diseases 40 certain 41 diseases despite compelling evidence linking protein carbonylation to numerous disorders , the underlying molecular mechanisms at the proteome remain to be identified . 0 ###LEFT-WALL### 14 mechanisms 0 ###LEFT-WALL### 18 remain 0 ###LEFT-WALL### 22 . 1 despite 3 evidence 1 despite 10 , 1 despite 14 mechanisms 2 compelling 3 evidence 3 evidence 4 linking 4 linking 6 carbonylation 4 linking 7 to 5 protein 6 carbonylation 7 to 9 disorders 8 numerous 9 disorders 11 the 14 mechanisms 12 underlying 14 mechanisms 13 molecular 14 mechanisms 14 mechanisms 15 at 14 mechanisms 18 remain 15 at 17 proteome 16 the 17 proteome 18 remain 19 to 19 to 20 be 20 be 21 identified recent advancements in analysis of ptms by mass spectrometry provided new insights into the mechanisms of protein carbonylation , such as protein susceptibility and exact modification sites , but only for a limited number of proteins . 0 ###LEFT-WALL### 2 advancements 0 ###LEFT-WALL### 10 provided 0 ###LEFT-WALL### 37 . 1 recent 2 advancements 2 advancements 3 in 2 advancements 7 by 2 advancements 10 provided 3 in 4 analysis 4 analysis 5 of 5 of 6 ptms 7 by 9 spectrometry 8 mass 9 spectrometry 10 provided 12 insights 10 provided 29 but 11 new 12 insights 13 into 15 mechanisms 13 into 29 but 14 the 15 mechanisms 15 mechanisms 16 of 15 mechanisms 21 as 16 of 18 carbonylation 17 protein 18 carbonylation 19 , 21 as 20 such 21 as 21 as 24 and 21 as 28 , 22 protein 23 susceptibility 23 susceptibility 24 and 24 and 27 sites 25 exact 26 modification 26 modification 27 sites 28 , 29 but 29 but 30 only 29 but 31 for 31 for 36 proteins 32 a 34 number 33 limited 34 number 34 number 35 of 34 number 36 proteins 35 of 36 proteins here we report the first proteome - wide study of carbonylated proteins including modification sites in hela cells for mild oxidative stress conditions . 0 ###LEFT-WALL### 2 we 0 ###LEFT-WALL### 3 report 0 ###LEFT-WALL### 24 . 1 here 2 we 2 we 3 report 3 report 9 study 3 report 16 in 4 the 5 first 4 the 9 study 6 proteome 7 - 6 proteome 9 study 8 wide 9 study 9 study 10 of 9 study 13 including 10 of 12 proteins 11 carbonylated 12 proteins 13 including 15 sites 14 modification 15 sites 16 in 18 cells 17 hela 18 cells 18 cells 19 for 19 for 23 conditions 20 mild 22 stress 21 oxidative 22 stress 22 stress 23 conditions the analysis relied on our recent strategy utilizing mass spectrometry - based enrichment of carbonylated peptides after dnph derivatization . 0 ###LEFT-WALL### 2 analysis 0 ###LEFT-WALL### 3 relied 0 ###LEFT-WALL### 20 . 1 the 2 analysis 2 analysis 3 relied 3 relied 4 on 4 on 7 strategy 5 our 7 strategy 6 recent 7 strategy 7 strategy 8 utilizing 8 utilizing 13 enrichment 8 utilizing 17 after 9 mass 13 enrichment 10 spectrometry 11 - 10 spectrometry 13 enrichment 12 based 13 enrichment 13 enrichment 14 of 14 of 16 peptides 15 carbonylated 16 peptides 17 after 19 derivatization 18 dnph 19 derivatization thus a total of 210 carbonylated proteins containing 643 carbonylation sites were consistently identified in three replicates . 0 ###LEFT-WALL### 3 total 0 ###LEFT-WALL### 6 carbonylated 0 ###LEFT-WALL### 18 . 1 thus 3 total 2 a 3 total 3 total 4 of 3 total 6 carbonylated 4 of 5 210 6 carbonylated 7 proteins 7 proteins 8 containing 8 containing 9 643 9 643 10 carbonylation 9 643 17 replicates 10 carbonylation 11 sites 10 carbonylation 12 were 10 carbonylation 14 identified 10 carbonylation 17 replicates 11 sites 12 were 13 consistently 14 identified 14 identified 15 in 15 in 16 three most carbonylation sites ( 284 , 44.2 % ) resulted from oxidation of lysine residues ( aminoadipic semialdehyde ) . 0 ###LEFT-WALL### 3 sites 0 ###LEFT-WALL### 10 resulted 0 ###LEFT-WALL### 20 . 1 most 3 sites 2 carbonylation 3 sites 3 sites 5 284 3 sites 8 % 3 sites 10 resulted 4 ( 5 284 5 284 6 , 6 , 8 % 7 44.2 8 % 8 % 9 ) 10 resulted 11 from 11 from 12 oxidation 12 oxidation 13 of 13 of 15 residues 14 lysine 15 residues 15 residues 18 semialdehyde 16 ( 18 semialdehyde 17 aminoadipic 18 semialdehyde 18 semialdehyde 19 ) additionally , 121 arginine ( 18.8 % ) , 121 threonine ( 18.8 % ) , [and] [117] proline residues ( 18.2 % ) were oxidized to reactive carbonyls . 0 ###LEFT-WALL### 4 arginine 0 ###LEFT-WALL### 26 oxidized 0 ###LEFT-WALL### 30 . 1 additionally 2 , 1 additionally 4 arginine 3 121 4 arginine 4 arginine 7 % 4 arginine 20 residues 4 arginine 25 were 5 ( 7 % 6 18.8 7 % 7 % 8 ) 9 , 20 residues 10 121 20 residues 11 threonine 14 % 11 threonine 16 , 11 threonine 20 residues 12 ( 14 % 13 18.8 14 % 14 % 15 ) 19 proline 20 residues 20 residues 23 % 20 residues 24 ) 21 ( 23 % 22 18.2 23 % 23 % 24 ) 25 were 26 oxidized 26 oxidized 27 to 27 to 29 carbonyls 28 reactive 29 carbonyls the sequence motifs were significantly enriched for lysine and arginine residues near carbonylation sites ( ±10 residues ) . 0 ###LEFT-WALL### 3 motifs 0 ###LEFT-WALL### 6 enriched 0 ###LEFT-WALL### 19 . 1 the 3 motifs 2 sequence 3 motifs 3 motifs 4 were 4 were 5 significantly 4 were 6 enriched 6 enriched 7 for 6 enriched 12 near 7 for 9 and 8 lysine 9 and 9 and 11 residues 10 arginine 11 residues 12 near 14 sites 13 carbonylation 14 sites 14 sites 17 residues 15 ( 17 residues 16 ±10 17 residues 17 residues 18 ) gene ontology analysis revealed that 80 % of the carbonylated proteins originated from organelles , 50 % enrichment of which was demonstrated for the nucleus . 0 ###LEFT-WALL### 3 analysis 0 ###LEFT-WALL### 4 revealed 0 ###LEFT-WALL### 15 , 0 ###LEFT-WALL### 26 . 1 gene 2 ontology 2 ontology 3 analysis 3 analysis 4 revealed 4 revealed 5 that 5 that 7 % 5 that 12 originated 6 80 7 % 7 % 8 of 7 % 12 originated 8 of 11 proteins 9 the 11 proteins 10 carbonylated 11 proteins 12 originated 13 from 13 from 14 organelles 15 , 18 enrichment 15 , 22 demonstrated 16 50 17 % 17 % 18 enrichment 18 enrichment 19 of 18 enrichment 21 was 19 of 20 which 21 was 22 demonstrated 22 demonstrated 23 for 23 for 25 nucleus 24 the 25 nucleus moreover , functional interactions between carbonylated proteins of kinetochore/spindle machinery and centrosome organization were significantly enriched . 0 ###LEFT-WALL### 4 interactions 0 ###LEFT-WALL### 16 enriched 0 ###LEFT-WALL### 17 . 1 moreover 2 , 1 moreover 4 interactions 3 functional 4 interactions 4 interactions 5 between 4 interactions 14 were 5 between 7 proteins 6 carbonylated 7 proteins 7 proteins 8 of 8 of 11 and 9 kinetochore/spindle 10 machinery 10 machinery 11 and 11 and 13 organization 12 centrosome 13 organization 14 were 15 significantly 14 were 16 enriched one - third of the 210 carbonylated proteins identified here are regulated during apoptosis . 0 ###LEFT-WALL### 1 one 0 ###LEFT-WALL### 2 - 2 - 8 proteins 2 - 12 regulated 2 - 15 . 3 third 8 proteins 4 of 6 210 4 of 8 proteins 5 the 6 210 6 210 7 carbonylated 8 proteins 9 identified 8 proteins 11 are 9 identified 10 here 11 are 12 regulated 12 regulated 13 during 13 during 14 apoptosis objectives : knowledge of the mechanical behaviour of root dentine can facilitate better understanding of spontaneous vertical root fracture [(] vrf [ )(, an age - related disease initiated mainly at the root apex . 0 ###LEFT-WALL### 1 objectives 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 35 . 2 : 3 knowledge 2 : 12 facilitate 2 : 27 related 3 knowledge 4 of 3 knowledge 11 can 4 of 7 behaviour 5 the 7 behaviour 6 mechanical 7 behaviour 7 behaviour 8 of 8 of 10 dentine 9 root 10 dentine 11 can 12 facilitate 12 facilitate 14 understanding 13 better 14 understanding 14 understanding 15 of 15 of 21 vrf 16 spontaneous 17 vertical 17 vertical 18 root 18 root 21 vrf 19 fracture 21 vrf 21 vrf 25 age 23 )(, 25 age 24 an 25 age 25 age 26 - 26 - 27 related 27 related 28 disease 27 related 30 mainly 28 disease 29 initiated 30 mainly 31 at 31 at 34 apex 32 the 34 apex 33 root 34 apex we tested the hypothesis that the biomechanical properties of root dentine change with ageing . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 tested 0 ###LEFT-WALL### 15 . 1 we 2 tested 2 tested 4 hypothesis 3 the 4 hypothesis 4 hypothesis 5 that 5 that 8 properties 5 that 12 change 6 the 8 properties 7 biomechanical 8 properties 8 properties 9 of 8 properties 12 change 9 of 11 dentine 10 root 11 dentine 12 change 13 with 13 with 14 ageing methods : sixteen human premolars were divided into " old " ( 17 - 30 years [ )(and " young " ( 50 - 80 years ) groups . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 29 . 2 : 5 premolars 2 : 7 divided 3 sixteen 5 premolars 4 human 5 premolars 5 premolars 6 were 6 were 7 divided 7 divided 8 into 8 into 9 " 8 into 18 )(and 10 old 11 " 10 old 13 17 10 old 14 - 10 old 16 years 12 ( 13 17 13 17 14 - 15 30 16 years 16 years 18 )(and 18 )(and 19 " 18 )(and 28 groups 20 young 21 " 20 young 26 years 20 young 27 ) 20 young 28 groups 22 ( 26 years 23 50 24 - 24 - 25 80 24 - 26 years 26 years 27 ) the elastic modulus , nano - hardness , micro - hardness , elemental contents , tubular density/area of root dentine in cervical , middle and apical root regions were evaluated using atomic force microscopy - based nano - indentation , knoop indentation , scanning electron microscopy and energy [dispersive] x - ray spectroscopy , respectively . 0 ###LEFT-WALL### 3 modulus 0 ###LEFT-WALL### 4 , 0 ###LEFT-WALL### 51 - 1 the 3 modulus 2 elastic 3 modulus 4 , 7 hardness 4 , 8 , 5 nano 6 - 5 nano 7 hardness 8 , 11 hardness 8 , 12 , 9 micro 10 - 9 micro 11 hardness 12 , 14 contents 12 , 36 based 12 , 38 - 13 elemental 14 contents 14 contents 17 density/area 14 contents 36 based 15 , 17 density/area 16 tubular 17 density/area 17 density/area 18 of 17 density/area 30 evaluated 17 density/area 35 - 18 of 20 dentine 19 root 20 dentine 20 dentine 21 in 21 in 25 and 22 cervical 23 , 23 , 24 middle 23 , 25 and 25 and 27 root 25 and 28 regions 25 and 29 were 26 apical 27 root 28 regions 29 were 30 evaluated 31 using 31 using 34 microscopy 32 atomic 33 force 33 force 34 microscopy 36 based 37 nano 38 - 39 indentation 38 - 40 , 40 , 42 indentation 40 , 43 , 41 knoop 42 indentation 43 , 47 and 44 scanning 45 electron 45 electron 46 microscopy 46 microscopy 47 and 47 and 48 energy 48 energy 50 x 50 x 51 - 51 - 52 ray 52 ray 53 spectroscopy 52 ray 55 respectively 54 , 55 respectively 55 respectively 56 . compared with young dentine , old dentine showed a greater hardness , a higher elastic modulus , a greater mineral content and a smaller tubular size in the cervical portion , whereas the age - induced changes in tubular density were insignificant . 0 ###LEFT-WALL### 7 dentine 0 ###LEFT-WALL### 8 showed 0 ###LEFT-WALL### 31 , 0 ###LEFT-WALL### 43 . 1 compared 2 with 1 compared 5 , 1 compared 7 dentine 2 with 4 dentine 3 young 4 dentine 6 old 7 dentine 7 dentine 8 showed 8 showed 11 hardness 8 showed 21 content 8 showed 22 and 8 showed 27 in 9 a 11 hardness 10 greater 11 hardness 11 hardness 16 modulus 12 , 16 modulus 13 a 16 modulus 14 higher 16 modulus 15 elastic 16 modulus 16 modulus 17 , 18 a 21 content 19 greater 20 mineral 20 mineral 21 content 22 and 26 size 23 a 26 size 24 smaller 26 size 25 tubular 26 size 27 in 30 portion 28 the 30 portion 29 cervical 30 portion 31 , 37 changes 31 , 41 were 32 whereas 34 age 32 whereas 35 - 32 whereas 37 changes 33 the 34 age 36 induced 37 changes 37 changes 38 in 37 changes 41 were 38 in 40 density 39 tubular 40 density 41 were 42 insignificant finite element analysis revealed that due to its higher elastic modulus , old apical dentine has a higher stress level than young dentine . 0 ###LEFT-WALL### 3 analysis 0 ###LEFT-WALL### 20 level 0 ###LEFT-WALL### 24 . 1 finite 2 element 2 element 3 analysis 3 analysis 4 revealed 4 revealed 5 that 5 that 15 dentine 5 that 16 has 6 due 7 to 7 to 11 modulus 7 to 12 , 7 to 15 dentine 8 its 11 modulus 9 higher 11 modulus 10 elastic 11 modulus 13 old 15 dentine 14 apical 15 dentine 15 dentine 16 has 16 has 19 stress 16 has 20 level 17 a 19 stress 18 higher 19 stress 20 level 21 than 21 than 23 dentine 22 young 23 dentine conclusions : the intrinsic material properties of root dentine have spatial variations , and they are altered by ageing . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 6 properties 2 : 10 have 2 : 14 and 2 : 20 . 3 the 6 properties 4 intrinsic 5 material 5 material 6 properties 6 properties 7 of 6 properties 10 have 7 of 9 dentine 8 root 9 dentine 10 have 12 variations 11 spatial 12 variations 13 , 14 and 14 and 15 they 14 and 17 altered 15 they 16 are 16 are 17 altered 17 altered 18 by 18 by 19 ageing the higher stress level in old apical dentine may be one reason , [if] not the most important one , why spontaneous vrfs are more likely to occur in the elderly population . 0 ###LEFT-WALL### 4 level 0 ###LEFT-WALL### 10 be 0 ###LEFT-WALL### 13 , 0 ###LEFT-WALL### 33 . 1 the 4 level 2 higher 3 stress 3 stress 4 level 4 level 5 in 4 level 9 may 5 in 8 dentine 6 old 8 dentine 7 apical 8 dentine 9 may 10 be 10 be 12 reason 11 one 12 reason 13 , 23 vrfs 13 , 24 are 15 not 19 one 15 not 20 , 15 not 23 vrfs 16 the 19 one 17 most 18 important 18 important 19 one 21 why 23 vrfs 22 spontaneous 23 vrfs 23 vrfs 24 are 24 are 25 more 24 are 26 likely 26 likely 27 to 26 likely 28 occur 27 to 28 occur 28 occur 29 in 29 in 32 population 30 the 32 population 31 elderly 32 population almost 30 % of humans present [a] toxoplasma gondii positive antibody status and its prevalence increases with age . 0 ###LEFT-WALL### 3 % 0 ###LEFT-WALL### 6 present 0 ###LEFT-WALL### 19 . 1 almost 2 30 2 30 3 % 3 % 4 of 3 % 6 present 4 of 5 humans 6 present 13 and 6 present 17 with 8 toxoplasma 12 status 9 gondii 12 status 10 positive 11 antibody 11 antibody 12 status 12 status 13 and 13 and 16 increases 14 its 16 increases 15 prevalence 16 increases 17 with 18 age the central nervous system is the main target . 0 ###LEFT-WALL### 4 system 0 ###LEFT-WALL### 5 is 0 ###LEFT-WALL### 9 . 1 the 4 system 2 central 4 system 3 nervous 4 system 4 system 5 is 5 is 8 target 6 the 7 main 6 the 8 target however , little is known about the influence of asymptomatic i.e [.] latent toxoplasmosis on cognitive functions in humans . 0 ###LEFT-WALL### 3 little 0 ###LEFT-WALL### 5 known 0 ###LEFT-WALL### 20 . 1 however 2 , 1 however 3 little 3 little 4 is 4 is 5 known 5 known 6 about 5 known 15 on 5 known 18 in 6 about 8 influence 7 the 8 influence 8 influence 9 of 9 of 14 toxoplasmosis 10 asymptomatic 11 i.e 11 i.e 14 toxoplasmosis 13 latent 14 toxoplasmosis 15 on 17 functions 16 cognitive 17 functions 18 in 19 humans to investigate neurocognitive dysfunctions in asymptomatic older adults with t . gondii positive antibody status a double - blinded neuropsychological study was conducted . 0 ###LEFT-WALL### 1 to 0 ###LEFT-WALL### 2 investigate 0 ###LEFT-WALL### 11 . 1 to 2 investigate 2 investigate 4 dysfunctions 2 investigate 5 in 2 investigate 9 with 3 neurocognitive 4 dysfunctions 5 in 8 adults 6 asymptomatic 8 adults 7 older 8 adults 9 with 10 t 11 . 15 status 11 . 23 conducted 11 . 24 . 12 gondii 15 status 13 positive 14 antibody 14 antibody 15 status 15 status 21 study 15 status 22 was 15 status 23 conducted 16 a 17 double 16 a 21 study 17 double 18 - 17 double 21 study 19 blinded 21 study 20 neuropsychological 21 study 21 study 22 was the outcome measures were a computer - based working - memory [test] ( 2 - [back] ) and several standardized psychometric tests of memory and executive cognitive functions . 0 ###LEFT-WALL### 3 measures 0 ###LEFT-WALL### 4 were 0 ###LEFT-WALL### 18 and 0 ###LEFT-WALL### 29 . 1 the 3 measures 2 outcome 3 measures 3 measures 4 were 4 were 6 computer 5 a 6 computer 6 computer 10 - 7 - 10 - 8 based 9 working 9 working 10 - 10 - 11 memory 10 - 17 ) 11 memory 14 2 13 ( 14 2 14 2 15 - 18 and 19 several 18 and 20 standardized 19 several 20 standardized 20 standardized 22 tests 21 psychometric 22 tests 22 tests 23 of 23 of 25 and 24 memory 25 and 25 and 28 functions 26 executive 28 functions 27 cognitive 28 functions t - pos seniors showed [an] impairment of different aspects of memory . 0 ###LEFT-WALL### 1 t 0 ###LEFT-WALL### 2 - 0 ###LEFT-WALL### 13 . 1 t 2 - 2 - 4 seniors 3 pos 4 seniors 4 seniors 5 showed 5 showed 7 impairment 7 impairment 8 of 8 of 10 aspects 9 different 10 aspects 10 aspects 11 of 11 of 12 memory the rate of correctly detected target symbols in a 2 [-] back task was decreased by nearly 9 % ( p=0.020 ) , corresponding to a performance reduction of about 35 % in working memory relative to [the] t - neg group . 0 ###LEFT-WALL### 2 rate 0 ###LEFT-WALL### 15 decreased 0 ###LEFT-WALL### 40 - 1 the 2 rate 2 rate 3 of 2 rate 14 was 3 of 7 symbols 4 correctly 5 detected 5 detected 6 target 6 target 7 symbols 7 symbols 8 in 8 in 13 task 9 a 13 task 10 2 13 task 12 back 13 task 14 was 15 decreased 15 decreased 16 by 15 decreased 23 , 15 decreased 24 corresponding 16 by 19 % 17 nearly 18 9 18 9 19 % 19 % 21 p=0.020 20 ( 21 p=0.020 21 p=0.020 22 ) 24 corresponding 25 to 24 corresponding 33 in 25 to 28 reduction 26 a 28 reduction 27 performance 28 reduction 28 reduction 29 of 29 of 32 % 30 about 31 35 31 35 32 % 33 in 34 working 34 working 35 memory 35 memory 36 relative 36 relative 37 to 37 to 39 t 40 - 42 group 40 - 43 . 41 neg 42 group in contrast , executive functions were not affected . 0 ###LEFT-WALL### 5 functions 0 ###LEFT-WALL### 8 affected 0 ###LEFT-WALL### 9 . 1 in 2 contrast 1 in 3 , 1 in 5 functions 4 executive 5 functions 5 functions 6 were 6 were 7 not 6 were 8 affected the effects remained mostly unchanged after controlling for medication . 0 ###LEFT-WALL### 2 effects 0 ###LEFT-WALL### 3 remained 0 ###LEFT-WALL### 10 . 1 the 2 effects 2 effects 3 remained 3 remained 5 unchanged 4 mostly 5 unchanged 5 unchanged 6 after 6 after 7 controlling 7 controlling 8 for 8 for 9 medication the impairment of memory functions in t - pos seniors [was] accompanied by a decreased self - reported quality of life . 0 ###LEFT-WALL### 2 impairment 0 ###LEFT-WALL### 18 reported 0 ###LEFT-WALL### 22 . 1 the 2 impairment 2 impairment 3 of 2 impairment 18 reported 3 of 5 functions 4 memory 5 functions 5 functions 6 in 5 functions 10 seniors 6 in 7 t 8 - 10 seniors 9 pos 10 seniors 10 seniors 12 accompanied 10 seniors 17 - 12 accompanied 13 by 13 by 16 self 14 a 16 self 15 decreased 16 self 18 reported 19 quality 19 quality 20 of 20 of 21 life because of the high prevalence of asymptomatic toxoplasmosis and an increasing population of older adults this finding is of high relevance [for] public health . 0 ###LEFT-WALL### 17 finding 0 ###LEFT-WALL### 18 is 0 ###LEFT-WALL### 25 . 1 because 2 of 1 because 17 finding 2 of 9 and 3 the 5 prevalence 4 high 5 prevalence 5 prevalence 6 of 5 prevalence 9 and 6 of 8 toxoplasmosis 7 asymptomatic 8 toxoplasmosis 9 and 12 population 9 and 13 of 10 an 12 population 11 increasing 12 population 13 of 15 adults 14 older 15 adults 16 this 17 finding 17 finding 18 is 18 is 19 of 19 of 24 health 20 high 21 relevance 21 relevance 24 health 23 public 24 health a repeated measures microarray design with 22 healthy , [non] [-] smoking volunteers ( aging 32±5years ) was set up to study transcriptome profiles in whole blood samples . 0 ###LEFT-WALL### 5 design 0 ###LEFT-WALL### 22 study 0 ###LEFT-WALL### 29 . 1 a 5 design 2 repeated 3 measures 3 measures 4 microarray 4 microarray 5 design 5 design 6 with 5 design 12 smoking 5 design 13 volunteers 5 design 18 was 6 with 7 22 8 healthy 9 , 8 healthy 12 smoking 12 smoking 13 volunteers 13 volunteers 15 aging 14 ( 15 aging 15 aging 16 32±5years 15 aging 17 ) 18 was 19 set 19 set 20 up 19 set 21 to 21 to 22 study 22 study 24 profiles 22 study 25 in 23 transcriptome 24 profiles 25 in 28 samples 26 whole 28 samples 27 blood 28 samples the results indicate that repeatable data can be obtained [with] high [within] - subject correlation . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 indicate 0 ###LEFT-WALL### 13 - 1 the 2 results 2 results 3 indicate 3 indicate 4 that 4 that 6 data 4 that 9 obtained 5 repeatable 6 data 6 data 7 can 7 can 8 be 8 be 9 obtained 9 obtained 11 high 13 - 15 correlation 13 - 16 . 14 subject 15 correlation probes that could discriminate between individuals are associated with immune and inflammatory functions . 0 ###LEFT-WALL### 1 probes 0 ###LEFT-WALL### 8 associated 0 ###LEFT-WALL### 14 . 1 probes 2 that 1 probes 3 could 1 probes 7 are 2 that 3 could 3 could 4 discriminate 4 discriminate 5 between 5 between 6 individuals 7 are 8 associated 8 associated 9 with 9 with 13 functions 10 immune 11 and 11 and 12 inflammatory 11 and 13 functions when investigating possible time trends in the microarray data , we have found no differential expression within a sampling period ( within [-] season effect ) . 0 ###LEFT-WALL### 11 we 0 ###LEFT-WALL### 13 found 0 ###LEFT-WALL### 27 . 1 when 2 investigating 1 when 10 , 1 when 11 we 2 investigating 5 trends 2 investigating 6 in 3 possible 5 trends 4 time 5 trends 6 in 9 data 7 the 9 data 8 microarray 9 data 11 we 12 have 12 have 13 found 13 found 15 differential 13 found 16 expression 13 found 17 within 14 no 15 differential 17 within 20 period 18 a 20 period 19 sampling 20 period 20 period 22 within 21 ( 22 within 22 within 25 effect 22 within 26 ) 24 season 25 effect differential expression was observed between sampling seasons and the data suggest a weak response of genes related to immune system functioning . 0 ###LEFT-WALL### 2 expression 0 ###LEFT-WALL### 4 observed 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 22 . 1 differential 2 expression 2 expression 3 was 3 was 4 observed 4 observed 5 between 5 between 6 sampling 6 sampling 7 seasons 8 and 10 data 8 and 11 suggest 9 the 10 data 10 data 11 suggest 11 suggest 14 response 11 suggest 17 related 12 a 13 weak 12 a 14 response 13 weak 14 response 14 response 15 of 14 response 17 related 15 of 16 genes 17 related 18 to 18 to 21 functioning 19 immune 20 system 20 system 21 functioning finally , a high number of probes showed significant [season] - specific expression variability within subjects . 0 ###LEFT-WALL### 7 probes 0 ###LEFT-WALL### 8 showed 0 ###LEFT-WALL### 17 . 1 finally 2 , 1 finally 7 probes 3 a 4 high 3 a 5 number 4 high 5 number 5 number 6 of 5 number 7 probes 6 of 7 probes 7 probes 8 showed 8 showed 13 expression 8 showed 14 variability 8 showed 15 within 9 significant 11 - 9 significant 13 expression 12 specific 13 expression 15 within 16 subjects expression variability increased in springtime and there was an association of the probe list with immune system functioning . 0 ###LEFT-WALL### 2 variability 0 ###LEFT-WALL### 8 was 0 ###LEFT-WALL### 19 . 1 expression 2 variability 2 variability 3 increased 2 variability 6 and 2 variability 8 was 4 in 5 springtime 4 in 6 and 6 and 7 there 8 was 10 association 9 an 10 association 10 association 11 of 10 association 15 with 11 of 14 list 12 the 14 list 13 probe 14 list 15 with 18 functioning 16 immune 17 system 17 system 18 functioning our study suggests that the blood transcriptome of healthy individuals is reproducible over a time period of several months . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 suggests 0 ###LEFT-WALL### 20 . 1 our 2 study 2 study 3 suggests 3 suggests 4 that 4 that 7 transcriptome 4 that 11 is 5 the 7 transcriptome 6 blood 7 transcriptome 7 transcriptome 8 of 7 transcriptome 11 is 8 of 10 individuals 9 healthy 10 individuals 11 is 12 reproducible 12 reproducible 13 over 13 over 16 period 14 a 16 period 15 time 16 period 16 period 17 of 17 of 19 months 18 several 19 months menopause is the transition from reproductive [to] [non] - reproductive life well before natural death . 0 ###LEFT-WALL### 1 menopause 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 16 . 1 menopause 2 is 2 is 4 transition 3 the 4 transition 4 transition 5 from 5 from 12 well 6 reproductive 9 - 6 reproductive 11 life 10 reproductive 11 life 11 life 12 well 12 well 13 before 13 before 15 death 14 natural 15 death rather than involving a smooth , rapid change , it is normally preceded by a long period of erratic hormonal fluctuation that is accompanied by a plethora of unpleasant symptoms . 0 ###LEFT-WALL### 10 it 0 ###LEFT-WALL### 13 preceded 0 ###LEFT-WALL### 31 . 1 rather 2 than 2 than 3 involving 2 than 9 , 2 than 10 it 3 involving 8 change 4 a 5 smooth 4 a 8 change 5 smooth 6 , 5 smooth 8 change 7 rapid 8 change 10 it 11 is 11 is 13 preceded 12 normally 13 preceded 13 preceded 14 by 14 by 17 period 15 a 17 period 16 long 17 period 17 period 18 of 17 period 24 accompanied 18 of 21 fluctuation 19 erratic 21 fluctuation 20 hormonal 21 fluctuation 22 that 23 is 23 is 24 accompanied 24 accompanied 25 by 25 by 27 plethora 26 a 27 plethora 27 plethora 28 of 28 of 30 symptoms 29 unpleasant 30 symptoms sex steroids are central to sexual development and reproduction , exerting pleiotropic effects on multiple tissues and organs throughout the lifespan of humans . 0 ###LEFT-WALL### 2 steroids 0 ###LEFT-WALL### 3 are 1 sex 2 steroids 2 steroids 3 are 3 are 4 central 4 central 5 to 5 to 8 and 6 sexual 7 development 7 development 8 and 8 and 9 reproduction 8 and 11 exerting 10 , 11 exerting 11 exerting 13 effects 11 exerting 14 on 11 exerting 19 throughout 11 exerting 24 . 12 pleiotropic 13 effects 14 on 17 and 15 multiple 16 tissues 16 tissues 17 and 17 and 18 organs 19 throughout 21 lifespan 20 the 21 lifespan 21 lifespan 22 of 22 of 23 humans sex steroids are fundamental to skeletal development , bone homeostasis and immune function . 0 ###LEFT-WALL### 2 steroids 0 ###LEFT-WALL### 3 are 0 ###LEFT-WALL### 14 . 1 sex 2 steroids 2 steroids 3 are 3 are 4 fundamental 4 fundamental 5 to 5 to 11 and 6 skeletal 7 development 7 development 8 , 8 , 10 homeostasis 8 , 11 and 9 bone 10 homeostasis 11 and 13 function 12 immune 13 function the composite effect of sex - specific genetic architecture and circulating levels of sex - steroid hormones closely parallels differences in the immune response and may account for corresponding sex - related differences in risk for chronic periodontitis , with men exhibiting greater susceptibility than women . 0 ###LEFT-WALL### 3 effect 0 ###LEFT-WALL### 32 related 1 the 3 effect 2 composite 3 effect 3 effect 4 of 3 effect 32 related 4 of 5 sex 5 sex 10 and 6 - 10 and 7 specific 9 architecture 8 genetic 9 architecture 9 architecture 10 and 10 and 12 levels 10 and 13 of 10 and 31 - 11 circulating 12 levels 13 of 14 sex 14 sex 17 hormones 15 - 17 hormones 16 steroid 17 hormones 17 hormones 25 and 17 hormones 31 - 18 closely 19 parallels 19 parallels 20 differences 19 parallels 21 in 19 parallels 25 and 21 in 24 response 22 the 24 response 23 immune 24 response 25 and 26 may 25 and 30 sex 26 may 27 account 27 account 28 for 28 for 29 corresponding 32 related 33 differences 32 related 36 for 33 differences 34 in 34 in 35 risk 36 for 38 periodontitis 37 chronic 38 periodontitis 38 periodontitis 40 with 39 , 40 with 40 with 41 men 40 with 47 . 41 men 42 exhibiting 42 exhibiting 44 susceptibility 42 exhibiting 45 than 43 greater 44 susceptibility 45 than 46 women age - associated reductions in sex steroids also provide insight into apparent temporal increases in susceptibility to periodontitis and alveolar bone loss , particularly among women . 0 ###LEFT-WALL### 4 reductions 0 ###LEFT-WALL### 9 provide 0 ###LEFT-WALL### 27 . 1 age 2 - 1 age 4 reductions 3 associated 4 reductions 4 reductions 5 in 4 reductions 9 provide 5 in 7 steroids 6 sex 7 steroids 8 also 9 provide 9 provide 10 insight 9 provide 11 into 9 provide 15 in 9 provide 17 to 9 provide 24 particularly 11 into 14 increases 12 apparent 14 increases 13 temporal 14 increases 15 in 16 susceptibility 17 to 19 and 18 periodontitis 19 and 19 and 22 loss 19 and 23 , 20 alveolar 21 bone 21 bone 22 loss 24 particularly 25 among 25 among 26 women chronic infection and inflammatory conditions , such as periodontal disease , provide a unique platform for exploring the interface of sex steroids , immunity and bone metabolism . 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 12 provide 0 ###LEFT-WALL### 23 , 0 ###LEFT-WALL### 28 . 1 chronic 2 infection 2 infection 3 and 3 and 5 conditions 3 and 8 as 3 and 12 provide 4 inflammatory 5 conditions 6 , 8 as 7 such 8 as 8 as 10 disease 8 as 11 , 9 periodontal 10 disease 12 provide 15 platform 13 a 15 platform 14 unique 15 platform 15 platform 16 for 15 platform 20 of 16 for 17 exploring 17 exploring 19 interface 18 the 19 interface 20 of 22 steroids 21 sex 22 steroids 23 , 25 and 24 immunity 25 and 25 and 27 metabolism 26 bone 27 metabolism chronic inflammation is a prominent feature of aging and [of] common age - related diseases , including atherosclerosis , cancer and periodontitis . 0 ###LEFT-WALL### 2 inflammation 0 ###LEFT-WALL### 3 is 0 ###LEFT-WALL### 14 related 1 chronic 2 inflammation 2 inflammation 3 is 3 is 9 and 4 a 5 prominent 4 a 6 feature 5 prominent 6 feature 6 feature 7 of 6 feature 9 and 7 of 8 aging 9 and 12 age 11 common 12 age 13 - 14 related 14 related 21 and 14 related 23 . 15 diseases 16 , 16 , 18 atherosclerosis 16 , 19 , 17 including 18 atherosclerosis 19 , 20 cancer 19 , 21 and 21 and 22 periodontitis this volume examines modifiable risk factors for periodontitis and other chronic inflammatory diseases . 0 ###LEFT-WALL### 2 volume 0 ###LEFT-WALL### 3 examines 0 ###LEFT-WALL### 14 . 1 this 2 volume 2 volume 3 examines 3 examines 6 factors 4 modifiable 6 factors 5 risk 6 factors 6 factors 7 for 7 for 9 and 8 periodontitis 9 and 9 and 13 diseases 10 other 13 diseases 11 chronic 13 diseases 12 inflammatory 13 diseases oral bacterial communities and viral infections , particularly with cytomegalovirus and other herpesviruses , elicit distinct immune responses [and] are central in the initiation of periodontal diseases . 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 20 are 0 ###LEFT-WALL### 28 . 1 oral 3 communities 2 bacterial 3 communities 3 communities 4 and 4 and 5 viral 4 and 6 infections 4 and 15 elicit 4 and 20 are 6 infections 9 with 6 infections 15 elicit 7 , 8 particularly 7 , 9 with 9 with 11 and 9 with 14 , 10 cytomegalovirus 11 and 11 and 13 herpesviruses 12 other 13 herpesviruses 15 elicit 18 responses 16 distinct 18 responses 17 immune 18 responses 20 are 21 central 21 central 22 in 22 in 24 initiation 23 the 24 initiation 24 initiation 25 of 25 of 27 diseases 26 periodontal 27 diseases risk of disease is dynamic and changes in response to complex interactions of genetic , environmental and stochastic factors over the lifespan . 0 ###LEFT-WALL### 1 risk 0 ###LEFT-WALL### 6 and 0 ###LEFT-WALL### 23 . 1 risk 2 of 1 risk 6 and 2 of 3 disease 4 is 5 dynamic 4 is 6 and 6 and 7 changes 6 and 9 response 6 and 10 to 8 in 9 response 10 to 11 complex 11 complex 12 interactions 12 interactions 13 of 13 of 19 factors 14 genetic 15 , 15 , 16 environmental 15 , 17 and 17 and 18 stochastic 17 and 19 factors 19 factors 20 over 20 over 22 lifespan 21 the 22 lifespan many modifiable risk factors , such as smoking and excess caloric intake , contribute to increases in systemic markers of inflammation and can modify gene regulation through a variety of biologic mechanisms ( e.g [.] epigenetic modifications ) . 0 ###LEFT-WALL### 4 factors 0 ###LEFT-WALL### 22 and 0 ###LEFT-WALL### 39 . 1 many 4 factors 2 modifiable 4 factors 3 risk 4 factors 4 factors 7 as 4 factors 22 and 5 , 7 as 6 such 7 as 7 as 9 and 7 as 13 , 8 smoking 9 and 9 and 12 intake 10 excess 12 intake 11 caloric 12 intake 14 contribute 15 to 14 contribute 17 in 14 contribute 22 and 15 to 16 increases 17 in 19 markers 18 systemic 19 markers 19 markers 20 of 20 of 21 inflammation 22 and 23 can 22 and 27 through 23 can 24 modify 24 modify 26 regulation 25 gene 26 regulation 27 through 29 variety 28 a 29 variety 29 variety 30 of 29 variety 37 modifications 30 of 32 mechanisms 31 biologic 32 mechanisms 33 ( 37 modifications 34 e.g 37 modifications 36 epigenetic 37 modifications 37 modifications 38 ) periodontitis and other common chronic inflammatory diseases share multiple modifiable risk factors , such as tobacco smoking , psychological stress and depression , alcohol consumption , obesity , diabetes , metabolic syndrome and osteoporosis . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 8 share 1 periodontitis 2 and 2 and 7 diseases 2 and 8 share 3 other 7 diseases 4 common 7 diseases 5 chronic 7 diseases 6 inflammatory 7 diseases 8 share 12 factors 8 share 15 as 9 multiple 12 factors 10 modifiable 12 factors 11 risk 12 factors 13 , 15 as 14 such 15 as 15 as 21 and 15 as 35 . 16 tobacco 17 smoking 16 tobacco 18 , 18 , 20 stress 18 , 21 and 19 psychological 20 stress 21 and 22 depression 21 and 33 and 23 , 33 and 24 alcohol 25 consumption 25 consumption 26 , 26 , 27 obesity 26 , 28 , 28 , 29 diabetes 28 , 30 , 30 , 32 syndrome 30 , 33 and 31 metabolic 32 syndrome 33 and 34 osteoporosis 33 and 35 . interventions that target modifiable risk factors have the potential to improve risk profiles for periodontitis as well as for other common chronic diseases . 0 ###LEFT-WALL### 1 interventions 0 ###LEFT-WALL### 11 improve 0 ###LEFT-WALL### 24 . 1 interventions 2 that 1 interventions 3 target 1 interventions 11 improve 2 that 3 target 3 target 5 risk 4 modifiable 5 risk 5 risk 6 factors 5 risk 10 to 6 factors 7 have 7 have 9 potential 7 have 10 to 8 the 9 potential 11 improve 13 profiles 11 improve 17 well 11 improve 18 as 12 risk 13 profiles 13 profiles 14 for 14 for 15 periodontitis 16 as 17 well 18 as 19 for 19 for 23 diseases 20 other 23 diseases 21 common 23 diseases 22 chronic 23 diseases objective : effective [monitoring] and treatment are needed to address the elevated rates of medical comorbidity among individuals with serious mental illnesses . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 23 . 2 : 5 and 2 : 8 needed 3 effective 5 and 5 and 6 treatment 5 and 7 are 7 are 8 needed 8 needed 9 to 9 to 10 address 10 address 13 rates 11 the 13 rates 12 elevated 13 rates 13 rates 14 of 14 of 16 comorbidity 15 medical 16 comorbidity 16 comorbidity 17 among 17 among 18 individuals 18 individuals 19 with 19 with 22 illnesses 20 serious 22 illnesses 21 mental 22 illnesses this study examined the feasibility and potential effectiveness of an automated telehealth intervention , supported by nurse health - care management , among adults with serious mental illnesses and chronic medical conditions . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 examined 0 ###LEFT-WALL### 33 . 1 this 2 study 2 study 3 examined 3 examined 6 and 3 examined 15 supported 3 examined 23 among 4 the 5 feasibility 5 feasibility 6 and 6 and 8 effectiveness 6 and 9 of 7 potential 8 effectiveness 9 of 13 intervention 10 an 13 intervention 11 automated 13 intervention 12 telehealth 13 intervention 14 , 15 supported 15 supported 16 by 15 supported 22 , 16 by 18 health 17 nurse 18 health 18 health 21 management 19 - 21 management 20 care 21 management 21 management 22 , 23 among 29 and 24 adults 25 with 24 adults 29 and 25 with 28 illnesses 26 serious 28 illnesses 27 mental 28 illnesses 29 and 32 conditions 30 chronic 32 conditions 31 medical 32 conditions methods : we conducted a single - arm pilot trial with 70 individuals with serious mental illnesses and chronic medical conditions who were medically unstable ( determined by treatment team [or] defined as multiple emergency room visits/hospitalizations within the past year ) . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 3 we 2 : 4 conducted 2 : 43 . 3 we 4 conducted 4 conducted 18 and 5 a 10 trial 6 single 7 - 6 single 10 trial 8 arm 10 trial 9 pilot 10 trial 10 trial 11 with 10 trial 14 with 10 trial 18 and 11 with 13 individuals 12 70 13 individuals 14 with 17 illnesses 15 serious 17 illnesses 16 mental 17 illnesses 18 and 21 conditions 18 and 22 who 18 and 23 were 19 chronic 21 conditions 20 medical 21 conditions 22 who 23 were 23 were 24 medically 23 were 25 unstable 25 unstable 27 determined 26 ( 27 determined 27 determined 28 by 27 determined 38 within 27 determined 42 ) 28 by 37 visits/hospitalizations 29 treatment 32 defined 30 team 32 defined 32 defined 35 emergency 33 as 34 multiple 34 multiple 35 emergency 35 emergency 37 visits/hospitalizations 36 room 37 visits/hospitalizations 38 within 41 year 39 the 41 year 40 past 41 year the telehealth intervention was delivered for 6 months with feasibility and acceptability as the primary outcomes . 0 ###LEFT-WALL### 3 intervention 0 ###LEFT-WALL### 5 delivered 0 ###LEFT-WALL### 17 . 1 the 3 intervention 2 telehealth 3 intervention 3 intervention 4 was 4 was 5 delivered 5 delivered 6 for 5 delivered 9 with 5 delivered 13 as 6 for 8 months 7 6 8 months 9 with 11 and 10 feasibility 11 and 11 and 12 acceptability 13 as 16 outcomes 14 the 16 outcomes 15 primary 16 outcomes measures of illness management [self] - efficacy , psychiatric symptoms , subjective health status , health indicators , and service use were also collected at baseline and at 6 months . 0 ###LEFT-WALL### 19 and 0 ###LEFT-WALL### 22 were 0 ###LEFT-WALL### 31 . 1 measures 2 of 1 measures 19 and 2 of 4 management 3 illness 4 management 4 management 7 efficacy 4 management 10 symptoms 6 - 7 efficacy 7 efficacy 8 , 8 , 10 symptoms 9 psychiatric 10 symptoms 10 symptoms 14 status 10 symptoms 17 indicators 10 symptoms 18 , 11 , 14 status 12 subjective 13 health 13 health 14 status 14 status 15 , 15 , 17 indicators 16 health 17 indicators 17 indicators 18 , 18 , 19 and 19 and 21 use 19 and 22 were 20 service 21 use 22 were 23 also 22 were 24 collected 24 collected 27 and 25 at 26 baseline 25 at 27 and 27 and 28 at 28 at 30 months 29 6 30 months results : most individuals ( n = 62 ; 89 % [ )(participated in at least 70 % of the telehealth sessions . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 9 ; 0 ###LEFT-WALL### 23 . 1 results 2 : 2 : 4 individuals 3 most 4 individuals 4 individuals 7 = 5 ( 7 = 6 n 7 = 7 = 8 62 9 ; 11 % 9 ; 13 )(participated 10 89 11 % 11 % 13 )(participated 13 )(participated 14 in 14 in 18 % 15 at 16 least 16 least 17 70 17 70 18 % 18 % 19 of 19 of 22 sessions 20 the 22 sessions 21 telehealth 22 sessions participation was associated with improvements in self [-] efficacy for managing depression and diastolic blood pressure . 0 ###LEFT-WALL### 1 participation 0 ###LEFT-WALL### 3 associated 0 ###LEFT-WALL### 17 . 1 participation 2 was 2 was 3 associated 3 associated 4 with 3 associated 6 in 4 with 5 improvements 6 in 13 and 7 self 9 efficacy 9 efficacy 10 for 9 efficacy 13 and 10 for 11 managing 11 managing 12 depression 13 and 16 pressure 14 diastolic 15 blood 15 blood 16 pressure almost all participants [(] n = 68 ; 98 % [ )(rated their understanding of their medical condition as " much better " or " somewhat better " postintervention . 0 ###LEFT-WALL### 3 participants 0 ###LEFT-WALL### 6 = 0 ###LEFT-WALL### 8 ; 0 ###LEFT-WALL### 30 . 1 almost 2 all 2 all 3 participants 3 participants 6 = 5 n 6 = 6 = 7 68 8 ; 10 % 8 ; 12 )(rated 9 98 10 % 10 % 12 )(rated 12 )(rated 14 understanding 12 )(rated 19 as 13 their 14 understanding 14 understanding 15 of 15 of 18 condition 16 their 18 condition 17 medical 18 condition 19 as 20 " 19 as 29 postintervention 21 much 22 better 22 better 23 " 22 better 24 or 24 or 25 " 24 or 27 better 24 or 29 postintervention 26 somewhat 27 better 27 better 28 " among a subgroup of individuals with diabetes , decreases in fasting blood glucose were achieved , and among those with diabetes and major depression or bipolar disorder there were reductions in urgent care and primary care visits . 0 ###LEFT-WALL### 9 decreases 0 ###LEFT-WALL### 14 were 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 37 visits 0 ###LEFT-WALL### 38 . 1 among 3 subgroup 1 among 9 decreases 2 a 3 subgroup 3 subgroup 4 of 4 of 5 individuals 6 with 7 diabetes 6 with 8 , 6 with 9 decreases 9 decreases 10 in 9 decreases 14 were 10 in 13 glucose 11 fasting 12 blood 12 blood 13 glucose 14 were 15 achieved 16 , 17 and 17 and 25 or 17 and 29 were 18 among 22 and 18 among 25 or 19 those 20 with 19 those 22 and 20 with 21 diabetes 22 and 23 major 24 depression 25 or 25 or 27 disorder 25 or 28 there 25 or 29 were 26 bipolar 27 disorder 29 were 30 reductions 29 were 31 in 31 in 34 and 32 urgent 33 care 33 care 34 and 34 and 35 primary 34 and 36 care 34 and 37 visits 36 care 37 visits conclusions and implications for practice : these results demonstrate the feasibility and acceptability of automated telehealth supported by a nurse care manager and the potential effectiveness of this technology in improving self - management of psychiatric symptoms and chronic health conditions among these high - risk individuals . 0 ###LEFT-WALL### 5 practice 0 ###LEFT-WALL### 6 : 0 ###LEFT-WALL### 41 conditions 0 ###LEFT-WALL### 48 . 1 conclusions 2 and 2 and 3 implications 3 implications 4 for 4 for 5 practice 6 : 8 results 6 : 9 demonstrate 6 : 33 - 7 these 8 results 8 results 9 demonstrate 9 demonstrate 12 and 10 the 12 and 11 feasibility 12 and 12 and 32 self 13 acceptability 14 of 13 acceptability 23 and 14 of 16 telehealth 15 automated 16 telehealth 16 telehealth 17 supported 16 telehealth 18 by 18 by 22 manager 19 a 22 manager 20 nurse 22 manager 21 care 22 manager 23 and 26 effectiveness 23 and 27 of 23 and 32 self 24 the 26 effectiveness 25 potential 26 effectiveness 27 of 29 technology 28 this 29 technology 29 technology 30 in 30 in 31 improving 33 - 34 management 34 management 35 of 35 of 38 and 36 psychiatric 37 symptoms 37 symptoms 38 and 38 and 39 chronic 38 and 40 health 38 and 41 conditions 40 health 41 conditions 41 conditions 42 among 42 among 47 individuals 43 these 47 individuals 44 high 45 - 44 high 47 individuals 46 risk 47 individuals objectives : to assess the association [between] self - reported noncancer pain and 5 [-] year mortality . 0 ###LEFT-WALL### 1 objectives 0 ###LEFT-WALL### 2 : 2 : 3 to 2 : 4 assess 2 : 10 reported 2 : 18 . 3 to 4 assess 4 assess 8 self 5 the 8 self 6 association 8 self 9 - 10 reported 10 reported 13 and 11 noncancer 12 pain 12 pain 13 and 13 and 17 mortality 14 5 16 year 16 year 17 mortality design : cohort . 0 ###LEFT-WALL### 1 design 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 4 . 1 design 2 : 2 : 3 cohort setting : community - dwelling older adults . 0 ###LEFT-WALL### 1 setting 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 4 - 1 setting 2 : 2 : 3 community 4 - 7 adults 4 - 8 . 5 dwelling 7 adults 6 older 7 adults participants : canadian study of health and aging 1996 wave . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 2 : 2 : 10 wave 2 : 11 . 3 canadian 10 wave 4 study 5 of 4 study 7 and 5 of 6 health 7 and 8 aging 7 and 10 wave 8 aging 9 1996 measurements : registrar of vital statistics - established [5] - year mortality . 0 ###LEFT-WALL### 1 measurements 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 10 - 0 ###LEFT-WALL### 13 . 1 measurements 2 : 2 : 3 registrar 3 registrar 4 of 4 of 6 statistics 5 vital 6 statistics 6 statistics 8 established 7 - 8 established 8 established 10 - 10 - 12 mortality 11 year 12 mortality noncancer pain was assessed using the 5 [-] point verbal descriptor scale , dichotomized into no [or] very mild [versus] moderate , severe , or very severe pain . 0 ###LEFT-WALL### 2 pain 0 ###LEFT-WALL### 4 assessed 0 ###LEFT-WALL### 22 , 0 ###LEFT-WALL### 29 . 1 noncancer 2 pain 2 pain 3 was 3 was 4 assessed 4 assessed 5 using 5 using 12 scale 6 the 12 scale 7 5 9 point 9 point 12 scale 10 verbal 11 descriptor 11 descriptor 12 scale 12 scale 14 dichotomized 13 , 14 dichotomized 14 dichotomized 15 into 14 dichotomized 22 , 15 into 21 moderate 16 no 21 moderate 18 very 19 mild 19 mild 21 moderate 22 , 28 pain 23 severe 25 or 24 , 25 or 25 or 27 severe 25 or 28 pain 26 very 27 severe frailty was the accumulation of health deficits . 0 ###LEFT-WALL### 1 frailty 0 ###LEFT-WALL### 2 was 0 ###LEFT-WALL### 8 . 1 frailty 2 was 2 was 4 accumulation 3 the 4 accumulation 4 accumulation 5 of 5 of 7 deficits 6 health 7 deficits cognitive status ( [modified] mini - mental state examination ) and depressed [mood] ( five - item mental health screening questionnaire ) were also assessed . 0 ###LEFT-WALL### 2 status 0 ###LEFT-WALL### 25 assessed 0 ###LEFT-WALL### 26 . 1 cognitive 2 status 2 status 11 and 2 status 23 were 3 ( 11 and 5 mini 9 examination 5 mini 11 and 6 - 9 examination 7 mental 8 state 8 state 9 examination 9 examination 10 ) 11 and 21 questionnaire 11 and 22 ) 12 depressed 15 five 12 depressed 16 - 12 depressed 17 item 14 ( 15 five 15 five 16 - 17 item 19 health 18 mental 19 health 19 health 21 questionnaire 20 screening 21 questionnaire 23 were 25 assessed 24 also 25 assessed multivariable logistic regression and cox proportional hazards were used to analyze the relationship between pain and 5 [-] year mortality . 0 ###LEFT-WALL### 16 and 0 ###LEFT-WALL### 21 . 1 multivariable 3 regression 2 logistic 3 regression 3 regression 4 and 4 and 5 cox 4 and 7 hazards 4 and 11 analyze 4 and 16 and 6 proportional 7 hazards 7 hazards 8 were 8 were 9 used 9 used 10 to 9 used 11 analyze 10 to 11 analyze 11 analyze 13 relationship 11 analyze 14 between 12 the 13 relationship 14 between 15 pain 16 and 20 mortality 17 5 19 year 19 year 20 mortality results : of 5,703 participants , 4,694 ( 82.3 % ) had complete data for analysis ; 1,663 of these ( 35.4 % ) reported moderate , severe , or very severe pain , and 1,343 ( 28.6 % ) had died at 5 - [year] follow - up . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 50 . 2 : 7 4,694 2 : 12 had 2 : 17 ; 2 : 45 - 3 of 5 participants 3 of 6 , 3 of 7 4,694 4 5,703 5 participants 7 4,694 10 % 7 4,694 12 had 8 ( 10 % 9 82.3 10 % 10 % 11 ) 12 had 14 data 13 complete 14 data 14 data 15 for 15 for 16 analysis 17 ; 18 1,663 17 ; 35 and 18 1,663 19 of 18 1,663 23 % 18 1,663 25 reported 19 of 20 these 21 ( 23 % 22 35.4 23 % 23 % 24 ) 25 reported 33 pain 26 moderate 27 , 26 moderate 33 pain 28 severe 30 or 29 , 30 or 30 or 32 severe 30 or 33 pain 31 very 32 severe 34 , 35 and 35 and 36 1,343 35 and 42 died 36 1,343 39 % 36 1,343 41 had 37 ( 39 % 38 28.6 39 % 39 % 40 ) 41 had 42 died 42 died 43 at 43 at 44 5 45 - 47 follow 45 - 48 - 48 - 49 up four hundred ninety - six of those who died ( 29.8 % ) reported moderate , severe , or very severe pain [and] 847 ( 27.9 % ) [no] or very mild pain . 0 ###LEFT-WALL### 3 ninety 0 ###LEFT-WALL### 15 moderate 0 ###LEFT-WALL### 16 , 0 ###LEFT-WALL### 34 . 1 four 2 hundred 2 hundred 3 ninety 3 ninety 15 moderate 4 - 14 reported 5 six 6 of 5 six 14 reported 6 of 7 those 7 those 8 who 7 those 9 died 7 those 12 % 8 who 9 died 10 ( 12 % 11 29.8 12 % 12 % 13 ) 14 reported 15 moderate 16 , 30 or 17 severe 19 or 18 , 19 or 19 or 22 pain 19 or 27 % 19 or 30 or 20 very 21 severe 21 severe 22 pain 22 pain 24 847 25 ( 27 % 26 27.9 27 % 27 % 28 ) 30 or 33 pain 31 very 32 mild 32 mild 33 pain multivariate logistic analysis found that individuals with moderate , severe , or very severe pain had lower odds of 5 [-] year mortality than those with no [or] very mild pain ( odds ratio=0.78 , 95 % confidence interval [(] ci )=0.66 - 0.92 ; p<.001 [ )( 0 ###LEFT-WALL### 3 analysis 0 ###LEFT-WALL### 4 found 0 ###LEFT-WALL### 45 ; 0 ###LEFT-WALL### 48 )( 1 multivariate 3 analysis 2 logistic 3 analysis 3 analysis 4 found 4 found 5 that 5 that 6 individuals 5 that 16 had 6 individuals 7 with 6 individuals 16 had 7 with 15 pain 8 moderate 9 , 9 , 10 severe 9 , 12 or 11 , 12 or 12 or 14 severe 12 or 15 pain 13 very 14 severe 16 had 18 odds 16 had 24 than 16 had 26 with 17 lower 18 odds 18 odds 19 of 19 of 23 mortality 20 5 22 year 22 year 23 mortality 24 than 25 those 26 with 31 pain 26 with 44 0.92 27 no 31 pain 29 very 30 mild 30 mild 31 pain 31 pain 34 ratio=0.78 31 pain 42 )=0.66 32 ( 34 ratio=0.78 33 odds 34 ratio=0.78 34 ratio=0.78 35 , 35 , 42 )=0.66 36 95 37 % 37 % 39 interval 38 confidence 39 interval 39 interval 42 )=0.66 41 ci 42 )=0.66 42 )=0.66 43 - 45 ; 46 p<.001 the risk of death was lower in persons reporting moderate or greater pain than in those with no [or] very mild pain ( hr=0.85 , 95 % ci=0.75 - 0.96 ; p=.01 [ )( 0 ###LEFT-WALL### 2 risk 0 ###LEFT-WALL### 5 was 0 ###LEFT-WALL### 25 , 1 the 2 risk 2 risk 3 of 2 risk 5 was 3 of 4 death 5 was 6 lower 6 lower 7 in 6 lower 15 in 6 lower 17 with 7 in 8 persons 8 persons 9 reporting 9 reporting 13 pain 9 reporting 14 than 10 moderate 11 or 11 or 12 greater 11 or 13 pain 15 in 16 those 17 with 22 pain 18 no 22 pain 20 very 21 mild 21 mild 22 pain 22 pain 24 hr=0.85 23 ( 24 hr=0.85 24 hr=0.85 25 , 25 , 28 ci=0.75 25 , 29 - 26 95 28 ci=0.75 27 % 28 ci=0.75 29 - 30 0.96 29 - 31 ; 29 - 34 )( 31 ; 32 p=.01 an interaction between pain and sex explained this effect . 0 ###LEFT-WALL### 2 interaction 0 ###LEFT-WALL### 7 explained 0 ###LEFT-WALL### 10 . 1 an 2 interaction 2 interaction 3 between 2 interaction 7 explained 3 between 5 and 4 pain 5 and 5 and 6 sex 7 explained 9 effect 8 this 9 effect men with pain were not significantly more likely than men [without] pain to die ( hr=1.00 , 95 % ci=0.84 - 1.19 [;] p=.99 ) , [whereas] women without pain ( hr=0.54 , 95 [%] [ci=0.47] - 0.63 [;] [p<0.01] ) [and] women with pain ( hr=0.40 [;] ci=0.33 - 0.47 [;] p<.01 ) had less risk of death than men [without] and [with] pain , respectively . 0 ###LEFT-WALL### 1 men 0 ###LEFT-WALL### 4 were 0 ###LEFT-WALL### 9 than 1 men 2 with 1 men 4 were 2 with 3 pain 4 were 5 not 4 were 6 significantly 4 were 8 likely 5 not 6 significantly 7 more 8 likely 8 likely 9 than 9 than 10 men 9 than 12 pain 10 men 12 pain 12 pain 13 to 12 pain 20 ci=0.84 13 to 14 die 14 die 16 hr=1.00 15 ( 16 hr=1.00 16 hr=1.00 17 , 18 95 20 ci=0.84 19 % 20 ci=0.84 20 ci=0.84 24 p=.99 20 ci=0.84 28 women 21 - 24 p=.99 22 1.19 24 p=.99 24 p=.99 25 ) 26 , 28 women 28 women 29 without 28 women 33 , 29 without 30 pain 30 pain 32 hr=0.54 31 ( 32 hr=0.54 32 hr=0.54 33 , 33 , 37 - 34 95 37 - 37 - 38 0.63 37 - 41 ) 37 - 43 women 43 women 44 with 43 women 55 had 44 with 45 pain 45 pain 49 ci=0.33 45 pain 53 p<.01 46 ( 49 ci=0.33 47 hr=0.40 49 ci=0.33 49 ci=0.33 50 - 50 - 53 p<.01 51 0.47 53 p<.01 53 p<.01 54 ) 55 had 56 less 55 had 57 risk 55 had 60 than 55 had 67 respectively 57 risk 58 of 58 of 59 death 60 than 63 and 61 men 63 and 63 and 65 pain 66 , 67 respectively 67 respectively 68 . conclusion : older women with pain were less likely to die within 5 years than older women without pain , men in pain , or men without pain . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 29 . 2 : 4 women 2 : 7 were 3 older 4 women 4 women 5 with 4 women 7 were 5 with 6 pain 7 were 9 likely 8 less 9 likely 9 likely 10 to 9 likely 11 die 10 to 11 die 11 die 12 within 11 die 15 than 12 within 14 years 13 5 14 years 15 than 17 women 15 than 18 without 16 older 17 women 18 without 25 or 19 pain 20 , 20 , 21 men 20 , 25 or 21 men 22 in 22 in 23 pain 24 , 25 or 25 or 26 men 26 men 27 without 27 without 28 pain the metabolic syndrome ( mets ) , a cluster of risk factors for cardiovascular disease and type 2 diabetes , has become an important public health problem . 0 ###LEFT-WALL### 3 syndrome 0 ###LEFT-WALL### 22 become 0 ###LEFT-WALL### 28 . 1 the 3 syndrome 2 metabolic 3 syndrome 3 syndrome 5 mets 3 syndrome 9 cluster 3 syndrome 21 has 4 ( 5 mets 5 mets 6 ) 7 , 9 cluster 8 a 9 cluster 9 cluster 10 of 9 cluster 20 , 10 of 12 factors 11 risk 12 factors 12 factors 13 for 13 for 16 and 14 cardiovascular 15 disease 15 disease 16 and 16 and 19 diabetes 17 type 19 diabetes 18 2 19 diabetes 21 has 22 become 22 become 27 problem 23 an 24 important 23 an 27 problem 24 important 26 health 25 public 26 health 26 health 27 problem considerable differences in the prevalence of the mets in human immunodeficiency virus ( hiv [ )(- infected subjects have been reported , as a consequence of several limitations regarding the diagnostic critera for mets . 0 ###LEFT-WALL### 2 differences 0 ###LEFT-WALL### 21 reported 0 ###LEFT-WALL### 22 , 0 ###LEFT-WALL### 35 . 1 considerable 2 differences 2 differences 3 in 2 differences 6 of 2 differences 9 in 2 differences 19 have 3 in 5 prevalence 4 the 5 prevalence 6 of 8 mets 7 the 8 mets 9 in 11 immunodeficiency 10 human 11 immunodeficiency 11 immunodeficiency 12 virus 11 immunodeficiency 17 infected 12 virus 14 hiv 12 virus 17 infected 13 ( 14 hiv 14 hiv 16 )(- 17 infected 18 subjects 19 have 20 been 20 been 21 reported 22 , 28 limitations 22 , 32 critera 23 as 25 consequence 23 as 28 limitations 24 a 25 consequence 25 consequence 26 of 26 of 27 several 28 limitations 29 regarding 28 limitations 32 critera 29 regarding 31 diagnostic 30 the 31 diagnostic 32 critera 33 for 33 for 34 mets new evidence suggests that the use of optimal waist cut [-] [off] points specific for the various ethnic populations could represent a step forward in overcoming these limitations . 0 ###LEFT-WALL### 2 evidence 0 ###LEFT-WALL### 3 suggests 0 ###LEFT-WALL### 29 . 1 new 2 evidence 2 evidence 3 suggests 3 suggests 4 that 4 that 6 use 4 that 21 represent 5 the 6 use 6 use 7 of 6 use 14 specific 6 use 20 could 7 of 13 points 8 optimal 10 cut 9 waist 10 cut 10 cut 13 points 14 specific 15 for 15 for 19 populations 16 the 19 populations 17 various 19 populations 18 ethnic 19 populations 20 could 21 represent 21 represent 24 forward 22 a 24 forward 23 step 24 forward 24 forward 25 in 25 in 26 overcoming 26 overcoming 28 limitations 27 these 28 limitations [also] the use [of] specific cut - off points for measuring upper trunk fat as an adjunctive criterion of mets in hiv patients with lipodystrophy could represent an interesting new research topic . 0 ###LEFT-WALL### 6 cut 0 ###LEFT-WALL### 7 - 2 the 6 cut 3 use 6 cut 5 specific 6 cut 7 - 23 patients 7 - 27 represent 7 - 33 . 8 off 9 points 8 off 23 patients 9 points 10 for 10 for 11 measuring 11 measuring 14 fat 11 measuring 15 as 11 measuring 21 in 12 upper 14 fat 13 trunk 14 fat 15 as 18 criterion 16 an 17 adjunctive 16 an 18 criterion 17 adjunctive 18 criterion 18 criterion 19 of 19 of 20 mets 21 in 22 hiv 23 patients 24 with 23 patients 26 could 24 with 25 lipodystrophy 26 could 27 represent 27 represent 32 topic 28 an 29 interesting 28 an 32 topic 29 interesting 31 research 30 new 31 research 31 research 32 topic although metabolic disorders have been associated indirectly with highly active antiretroviral therapy ( haart [ )(, directly with hiv infection per se or with host conditions , current circumstances could change the framework of mets in the hiv setting : for example , the aging hiv population and newer , less metabolically toxic antiretroviral drugs . 0 ###LEFT-WALL### 38 hiv 0 ###LEFT-WALL### 40 : 0 ###LEFT-WALL### 56 . 1 although 3 disorders 1 although 27 , 1 although 38 hiv 2 metabolic 3 disorders 3 disorders 27 , 4 have 5 been 4 have 27 , 5 been 6 associated 6 associated 7 indirectly 6 associated 8 with 6 associated 17 directly 6 associated 18 with 6 associated 23 or 8 with 12 therapy 9 highly 10 active 10 active 12 therapy 11 antiretroviral 12 therapy 12 therapy 14 haart 13 ( 14 haart 14 haart 16 )(, 18 with 20 infection 19 hiv 20 infection 21 per 22 se 22 se 23 or 23 or 24 with 24 with 26 conditions 25 host 26 conditions 27 , 31 change 28 current 29 circumstances 29 circumstances 30 could 30 could 31 change 31 change 33 framework 31 change 36 in 32 the 33 framework 33 framework 34 of 34 of 35 mets 37 the 38 hiv 38 hiv 39 setting 38 hiv 40 : 40 : 42 example 40 : 48 and 41 for 42 example 42 example 43 , 44 the 48 and 45 aging 47 population 46 hiv 47 population 47 population 48 and 48 and 55 drugs 49 newer 50 , 49 newer 55 drugs 51 less 52 metabolically 52 metabolically 53 toxic 53 toxic 55 drugs 54 antiretroviral 55 drugs lipotoxicity and adipokines have been focused as key issues for explaining mets in hiv patients . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 6 focused 0 ###LEFT-WALL### 16 . 1 lipotoxicity 2 and 2 and 3 adipokines 2 and 4 have 4 have 5 been 5 been 6 focused 6 focused 7 as 7 as 9 issues 8 key 9 issues 9 issues 10 for 10 for 11 explaining 11 explaining 12 mets 11 explaining 13 in 13 in 15 patients 14 hiv 15 patients several studies have investigated the pathophysiology of mets and cardiovascular complications in hiv infection . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 4 investigated 0 ###LEFT-WALL### 15 . 1 several 2 studies 2 studies 3 have 3 have 4 investigated 4 investigated 6 pathophysiology 4 investigated 12 in 5 the 6 pathophysiology 6 pathophysiology 7 of 7 of 9 and 8 mets 9 and 9 and 11 complications 10 cardiovascular 11 complications 12 in 14 infection 13 hiv 14 infection evidence shows [that] both hiv infection per se and hiv - related chronic immune activation despite antiretroviral therapy are critical factors linking mets and cardiovascular complications . 0 ###LEFT-WALL### 1 evidence 0 ###LEFT-WALL### 2 shows 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 27 . 1 evidence 2 shows 2 shows 4 both 2 shows 6 infection 2 shows 8 se 5 hiv 6 infection 7 per 8 se 9 and 10 hiv 9 and 19 are 10 hiv 19 are 11 - 12 related 12 related 15 activation 12 related 16 despite 12 related 19 are 13 chronic 15 activation 14 immune 15 activation 16 despite 18 therapy 17 antiretroviral 18 therapy 19 are 21 factors 20 critical 21 factors 21 factors 22 linking 22 linking 24 and 23 mets 24 and 24 and 26 complications 25 cardiovascular 26 complications current epidemiological and pathogenetic data on mets in hiv infection , prevention strategies and therapeutic options for all mets components are reviewed in the light of the recent adult treatment panel iv recommendations and the new antiretroviral drugs . 0 ###LEFT-WALL### 5 data 0 ###LEFT-WALL### 22 reviewed 0 ###LEFT-WALL### 39 . 1 current 5 data 2 epidemiological 3 and 3 and 4 pathogenetic 3 and 5 data 5 data 6 on 5 data 17 for 5 data 21 are 6 on 14 and 7 mets 8 in 7 mets 10 infection 8 in 9 hiv 10 infection 11 , 11 , 13 strategies 11 , 14 and 12 prevention 13 strategies 14 and 16 options 15 therapeutic 16 options 17 for 20 components 18 all 20 components 19 mets 20 components 21 are 22 reviewed 22 reviewed 23 in 23 in 34 and 24 the 25 light 25 light 26 of 25 light 34 and 26 of 33 recommendations 27 the 33 recommendations 28 recent 33 recommendations 29 adult 30 treatment 30 treatment 31 panel 31 panel 33 recommendations 32 iv 33 recommendations 34 and 38 drugs 35 the 38 drugs 36 new 38 drugs 37 antiretroviral 38 drugs [a] variety [of] chronic pathologies often come along with the aging process and [are] experienced by many patients in late adulthood . 0 ###LEFT-WALL### 5 pathologies 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 22 . 2 variety 5 pathologies 4 chronic 5 pathologies 5 pathologies 13 and 6 often 7 come 7 come 9 with 7 come 13 and 8 along 9 with 9 with 12 process 10 the 12 process 11 aging 12 process 13 and 15 experienced 13 and 16 by 13 and 19 in 16 by 18 patients 17 many 18 patients 19 in 21 adulthood 20 late 21 adulthood ems providers must be aware of the various challenges of transporting the geriatric population . 0 ###LEFT-WALL### 2 providers 0 ###LEFT-WALL### 4 be 0 ###LEFT-WALL### 15 . 1 ems 2 providers 2 providers 3 must 3 must 4 be 4 be 5 aware 5 aware 6 of 6 of 9 challenges 7 the 9 challenges 8 various 9 challenges 9 challenges 10 of 10 of 11 transporting 11 transporting 14 population 12 the 14 population 13 geriatric 14 population and although an emphasis is often placed on the physical and medical issues associated with this population , it 's also imperative to look at the whole picture to help prevent issues before they become an emegent problem . 0 ###LEFT-WALL### 1 and 0 ###LEFT-WALL### 20 's 0 ###LEFT-WALL### 39 . 1 and 19 it 1 and 20 's 2 although 4 emphasis 2 although 7 placed 2 although 19 it 3 an 4 emphasis 4 emphasis 5 is 5 is 6 often 5 is 7 placed 7 placed 8 on 7 placed 14 associated 8 on 11 and 9 the 10 physical 10 physical 11 and 11 and 13 issues 12 medical 13 issues 15 with 17 population 15 with 18 , 15 with 19 it 16 this 17 population 19 it 20 's 20 's 21 also 20 's 22 imperative 22 imperative 23 to 22 imperative 25 at 22 imperative 29 to 22 imperative 31 prevent 23 to 24 look 25 at 28 picture 26 the 28 picture 27 whole 28 picture 29 to 30 help 30 help 31 prevent 31 prevent 32 issues 31 prevent 33 before 33 before 34 they 33 before 35 become 34 they 35 become 35 become 38 problem 36 an 38 problem 37 emegent 38 problem this includes being vigilant for elder abuse and neglect , as well as potential home hazards - including fall potentials and maintaining colder home temperatures - and dangerous cost - cutting measures , such as sharing medications . 0 ###LEFT-WALL### 1 this 0 ###LEFT-WALL### 2 includes 0 ###LEFT-WALL### 10 , 0 ###LEFT-WALL### 38 . 1 this 2 includes 2 includes 3 being 3 being 4 vigilant 4 vigilant 5 for 5 for 8 and 6 elder 7 abuse 7 abuse 8 and 8 and 9 neglect 10 , 15 home 11 as 12 well 12 well 13 as 13 as 14 potential 13 as 15 home 15 home 16 hazards 15 home 18 including 15 home 35 as 17 - 18 including 18 including 27 and 18 including 33 , 19 fall 20 potentials 20 potentials 21 and 21 and 25 temperatures 21 and 27 and 22 maintaining 25 temperatures 23 colder 24 home 24 home 25 temperatures 26 - 27 and 27 and 29 cost 27 and 32 measures 28 dangerous 29 cost 30 - 32 measures 31 cutting 32 measures 32 measures 33 , 34 such 35 as 35 as 37 medications 36 sharing 37 medications prevention is key to helping older patients avoid potentially devastating situations , [such] [as] falls , medication errors and urban hyperthermia . 0 ###LEFT-WALL### 1 prevention 0 ###LEFT-WALL### 12 , 0 ###LEFT-WALL### 16 , 0 ###LEFT-WALL### 22 . 1 prevention 12 , 2 is 3 key 2 is 12 , 3 key 4 to 3 key 11 situations 4 to 5 helping 5 helping 7 patients 5 helping 10 devastating 6 older 7 patients 7 patients 8 avoid 8 avoid 10 devastating 9 potentially 10 devastating 12 , 15 falls 16 , 19 and 17 medication 18 errors 18 errors 19 and 19 and 21 hyperthermia 20 urban 21 hyperthermia but when those situations happen and providers are called to care for an older patient , compassion and demeanor are necessary to make this more vulnerable patient population comfortable and safe . 0 ###LEFT-WALL### 1 but 0 ###LEFT-WALL### 23 make 0 ###LEFT-WALL### 32 . 1 but 18 and 1 but 20 are 2 when 4 situations 2 when 6 and 2 when 16 , 2 when 18 and 3 those 4 situations 4 situations 6 and 5 happen 6 and 6 and 11 care 7 providers 8 are 8 are 9 called 9 called 10 to 10 to 11 care 11 care 12 for 12 for 15 patient 13 an 15 patient 14 older 15 patient 17 compassion 18 and 18 and 19 demeanor 18 and 20 are 20 are 21 necessary 21 necessary 22 to 22 to 23 make 23 make 28 population 23 make 30 and 24 this 28 population 25 more 26 vulnerable 26 vulnerable 28 population 27 patient 28 population 29 comfortable 30 and 30 and 31 safe oxidative stress plays a major role in the pathophysiology of chronic inflammatory disease and it has also been linked to accelerated telomere shortening . 0 ###LEFT-WALL### 2 stress 0 ###LEFT-WALL### 3 plays 0 ###LEFT-WALL### 14 and 0 ###LEFT-WALL### 24 . 1 oxidative 2 stress 2 stress 3 plays 3 plays 6 role 3 plays 7 in 4 a 5 major 4 a 6 role 5 major 6 role 7 in 9 pathophysiology 8 the 9 pathophysiology 9 pathophysiology 10 of 10 of 13 disease 11 chronic 13 disease 12 inflammatory 13 disease 14 and 15 it 14 and 19 linked 15 it 16 has 16 has 18 been 17 also 18 been 18 been 19 linked 19 linked 20 to 20 to 23 shortening 21 accelerated 23 shortening 22 telomere 23 shortening telomeres are [specialized] structures at the ends of linear chromosomes that protect these ends from degradation and fusion . 0 ###LEFT-WALL### 1 telomeres 0 ###LEFT-WALL### 2 are 0 ###LEFT-WALL### 19 . 1 telomeres 2 are 2 are 4 structures 2 are 5 at 5 at 7 ends 6 the 7 ends 7 ends 8 of 8 of 10 chromosomes 9 linear 10 chromosomes 10 chromosomes 11 that 10 chromosomes 12 protect 11 that 12 protect 12 protect 14 ends 12 protect 15 from 13 these 14 ends 15 from 17 and 16 degradation 17 and 17 and 18 fusion telomeres shorten with each cell division eventually leading to cellular senescence . 0 ###LEFT-WALL### 1 telomeres 0 ###LEFT-WALL### 2 shorten 0 ###LEFT-WALL### 12 . 1 telomeres 2 shorten 2 shorten 3 with 3 with 6 division 4 each 6 division 5 cell 6 division 6 division 8 leading 7 eventually 8 leading 8 leading 9 to 9 to 11 senescence 10 cellular 11 senescence research has shown that poly ( adp - ribose ) polymerase [-] 1 ( parp - 1 ) and subtelomeric methylation play a role in telomere stability . 0 ###LEFT-WALL### 1 research 0 ###LEFT-WALL### 3 shown 0 ###LEFT-WALL### 28 . 1 research 2 has 2 has 3 shown 3 shown 4 that 3 shown 5 poly 3 shown 8 - 3 shown 11 polymerase 3 shown 19 and 3 shown 25 in 6 ( 8 - 7 adp 8 - 8 - 9 ribose 8 - 10 ) 11 polymerase 13 1 11 polymerase 15 parp 14 ( 15 parp 15 parp 17 1 15 parp 18 ) 16 - 17 1 17 1 18 ) 19 and 22 play 19 and 24 role 20 subtelomeric 21 methylation 21 methylation 22 play 23 a 24 role 25 in 27 stability 26 telomere 27 stability we hypothesized that parp - 1 plays a role in accelerated aging in chronic inflammatory diseases due to its role [as] coactivator of nf - κb and ap - 1 . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 hypothesized 1 we 2 hypothesized 2 hypothesized 3 that 3 that 4 parp 3 that 11 accelerated 4 parp 6 1 4 parp 10 in 4 parp 11 accelerated 5 - 6 1 6 1 7 plays 7 plays 9 role 7 plays 10 in 8 a 9 role 11 accelerated 12 aging 12 aging 13 in 12 aging 18 to 12 aging 23 of 12 aging 27 and 13 in 16 diseases 14 chronic 16 diseases 15 inflammatory 16 diseases 17 due 18 to 18 to 22 coactivator 19 its 22 coactivator 20 role 22 coactivator 23 of 24 nf 25 - 27 and 26 κb 27 and 27 and 28 ap 27 and 31 . 28 ap 30 1 29 - 30 1 30 1 31 . therefore we evaluated the effect of chronic parp - 1 inhibition ( by fisetin and minocycline ) in human fibroblasts ( hf ) cultured under normal conditions and under conditions of chronic oxidative stress , induced by tert - butyl hydroperoxide [(] [t] - [bhp] ) . 0 ###LEFT-WALL### 2 we 0 ###LEFT-WALL### 3 evaluated 0 ###LEFT-WALL### 47 . 1 therefore 2 we 2 we 3 evaluated 3 evaluated 5 effect 4 the 5 effect 5 effect 6 of 5 effect 11 inhibition 6 of 8 parp 7 chronic 8 parp 9 - 11 inhibition 10 1 11 inhibition 11 inhibition 13 by 11 inhibition 46 ) 12 ( 13 by 13 by 15 and 13 by 44 - 14 fisetin 15 and 15 and 16 minocycline 15 and 17 ) 15 and 18 in 15 and 24 cultured 18 in 20 fibroblasts 19 human 20 fibroblasts 20 fibroblasts 22 hf 21 ( 22 hf 22 hf 23 ) 24 cultured 28 and 25 under 27 conditions 25 under 28 and 26 normal 27 conditions 28 and 29 under 29 under 30 conditions 30 conditions 31 of 31 of 34 stress 32 chronic 34 stress 33 oxidative 34 stress 34 stress 36 induced 35 , 36 induced 36 induced 37 by 36 induced 44 - 37 by 38 tert 38 tert 41 hydroperoxide 39 - 41 hydroperoxide 40 butyl 41 hydroperoxide 41 hydroperoxide 44 - results showed that parp - 1 inhibition under normal culturing conditions accelerated the rate of telomere shortening . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 showed 0 ###LEFT-WALL### 18 . 1 results 2 showed 2 showed 3 that 3 that 4 parp 3 that 12 accelerated 4 parp 7 inhibition 4 parp 11 conditions 4 parp 12 accelerated 5 - 6 1 6 1 7 inhibition 7 inhibition 8 under 7 inhibition 11 conditions 8 under 10 culturing 9 normal 10 culturing 12 accelerated 14 rate 13 the 14 rate 14 rate 15 of 15 of 16 telomere 16 telomere 17 shortening however , under conditions of chronic oxidative stress , parp - 1 inhibition did not show accelerated telomere shortening . 0 ###LEFT-WALL### 13 inhibition 0 ###LEFT-WALL### 16 show 0 ###LEFT-WALL### 20 . 1 however 2 , 1 however 13 inhibition 2 , 3 under 3 under 4 conditions 3 under 11 - 3 under 13 inhibition 4 conditions 5 of 5 of 8 stress 6 chronic 8 stress 7 oxidative 8 stress 8 stress 10 parp 9 , 10 parp 10 parp 11 - 12 1 13 inhibition 13 inhibition 14 did 14 did 15 not 14 did 16 show 16 show 19 shortening 17 accelerated 19 shortening 18 telomere 19 shortening we also observed a strong correlation between telomere length and subtelomeric methylation status of hf cells . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 observed 0 ###LEFT-WALL### 17 . 1 we 3 observed 2 also 3 observed 3 observed 6 correlation 3 observed 7 between 4 a 5 strong 4 a 6 correlation 5 strong 6 correlation 7 between 10 and 8 telomere 9 length 9 length 10 and 10 and 13 status 10 and 14 of 11 subtelomeric 12 methylation 12 methylation 13 status 14 of 16 cells 15 hf 16 cells we conclude that chronic parp - 1 inhibition appears to be beneficial in conditions of chronic oxidative stress but may be detrimental under relatively normal conditions . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 conclude 0 ###LEFT-WALL### 6 - 1 we 2 conclude 2 conclude 5 parp 3 that 4 chronic 4 chronic 5 parp 6 - 8 inhibition 6 - 9 appears 6 - 27 . 7 1 8 inhibition 8 inhibition 9 appears 9 appears 10 to 9 appears 19 but 10 to 19 but 11 be 12 beneficial 11 be 19 but 12 beneficial 13 in 13 in 14 conditions 14 conditions 15 of 15 of 18 stress 16 chronic 18 stress 17 oxidative 18 stress 19 but 20 may 20 may 21 be 21 be 22 detrimental 22 detrimental 23 under 23 under 26 conditions 24 relatively 25 normal 25 normal 26 conditions anemia is a common feature of hiv - related disease and has been uniformly demonstrated to be an independent predictor of morbidity and mortality . 0 ###LEFT-WALL### 1 anemia 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 8 - 0 ###LEFT-WALL### 15 demonstrated 0 ###LEFT-WALL### 25 . 1 anemia 2 is 2 is 5 feature 3 a 4 common 3 a 5 feature 4 common 5 feature 5 feature 6 of 6 of 7 hiv 8 - 11 and 9 related 10 disease 9 related 11 and 11 and 12 has 12 has 13 been 13 been 15 demonstrated 14 uniformly 15 demonstrated 15 demonstrated 16 to 16 to 17 be 17 be 20 predictor 18 an 20 predictor 19 independent 20 predictor 20 predictor 21 of 21 of 23 and 22 morbidity 23 and 23 and 24 mortality although anemia often responds to combination antiretroviral therapy , many patients remain anemic despite therapy and such persistent anemia [continues] to negatively affect [prognosis] regardless [of] [drug] [response] . 0 ###LEFT-WALL### 11 patients 0 ###LEFT-WALL### 12 remain 0 ###LEFT-WALL### 29 . 1 although 2 anemia 1 although 4 responds 1 although 9 , 1 although 11 patients 2 anemia 4 responds 3 often 4 responds 4 responds 5 to 5 to 8 therapy 6 combination 8 therapy 7 antiretroviral 8 therapy 10 many 11 patients 11 patients 12 remain 12 remain 13 anemic 13 anemic 14 despite 13 anemic 21 to 13 anemic 23 affect 14 despite 16 and 15 therapy 16 and 16 and 19 anemia 17 such 19 anemia 18 persistent 19 anemia 21 to 23 affect 22 negatively 23 affect 23 affect 25 regardless anemia is also a common feature of normal aging . 0 ###LEFT-WALL### 1 anemia 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 10 . 1 anemia 2 is 2 is 3 also 2 is 6 feature 4 a 5 common 4 a 6 feature 5 common 6 feature 6 feature 7 of 7 of 9 aging 8 normal 9 aging we postulate that the pathophysiology [of] anemia in hiv , especially that [which] persists in the face of combination antiretroviral therapy , is a reflection of underlying proinflammatory pathways that are also thought to contribute to anemia in the elderly , as well as other age - related chronic diseases such as cardiovascular disease and chronic obstructive pulmonary disease . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 10 , 1 we 2 postulate 2 postulate 3 that 3 that 5 pathophysiology 3 that 7 anemia 4 the 5 pathophysiology 5 pathophysiology 7 anemia 7 anemia 8 in 8 in 9 hiv 10 , 12 that 11 especially 12 that 12 that 22 , 14 persists 15 in 14 persists 22 , 15 in 17 face 16 the 17 face 17 face 18 of 18 of 21 therapy 19 combination 21 therapy 20 antiretroviral 21 therapy 22 , 23 is 22 , 34 to 23 is 25 reflection 24 a 25 reflection 25 reflection 26 of 26 of 27 underlying 27 underlying 29 pathways 28 proinflammatory 29 pathways 29 pathways 30 that 29 pathways 31 are 30 that 31 are 31 are 33 thought 32 also 33 thought 34 to 35 contribute 35 contribute 36 to 35 contribute 47 - 36 to 37 anemia 37 anemia 38 in 38 in 40 elderly 39 the 40 elderly 41 , 47 - 42 as 43 well 42 as 47 - 43 well 44 as 43 well 47 - 44 as 46 age 45 other 46 age 47 - 50 diseases 48 related 50 diseases 49 chronic 50 diseases 50 diseases 52 as 51 such 52 as 52 as 55 and 53 cardiovascular 54 disease 54 disease 55 and 55 and 59 disease 55 and 60 . 56 chronic 59 disease 57 obstructive 59 disease 58 pulmonary 59 disease this suggests that hiv induces inflammatory pathways that are associated with a pattern of accelerated aging and that anemia is a biomarker of these processes . 0 ###LEFT-WALL### 1 this 0 ###LEFT-WALL### 2 suggests 0 ###LEFT-WALL### 26 . 1 this 2 suggests 2 suggests 17 and 3 that 4 hiv 3 that 5 induces 3 that 17 and 4 hiv 5 induces 5 induces 7 pathways 6 inflammatory 7 pathways 7 pathways 8 that 7 pathways 9 are 8 that 9 are 9 are 10 associated 10 associated 11 with 11 with 13 pattern 12 a 13 pattern 13 pattern 14 of 14 of 16 aging 15 accelerated 16 aging 17 and 18 that 18 that 19 anemia 18 that 20 is 19 anemia 20 is 20 is 22 biomarker 21 a 22 biomarker 22 biomarker 23 of 23 of 25 processes 24 these 25 processes a better understanding of the pathophysiology of hiv - related anemia may provide important entry points for improving the chronic manifestations of hiv - related disease . 0 ###LEFT-WALL### 3 understanding 0 ###LEFT-WALL### 13 provide 0 ###LEFT-WALL### 25 related 0 ###LEFT-WALL### 27 . 1 a 3 understanding 2 better 3 understanding 3 understanding 4 of 3 understanding 7 of 3 understanding 12 may 4 of 6 pathophysiology 5 the 6 pathophysiology 7 of 8 hiv 9 - 10 related 10 related 11 anemia 10 related 12 may 12 may 13 provide 13 provide 16 points 13 provide 17 for 14 important 15 entry 15 entry 16 points 17 for 18 improving 18 improving 21 manifestations 19 the 21 manifestations 20 chronic 21 manifestations 21 manifestations 22 of 22 of 23 hiv 24 - 25 related 25 related 26 disease the management of chronic lymphocytic leukemia ( cll ) is undergoing profound changes . 0 ###LEFT-WALL### 2 management 0 ###LEFT-WALL### 10 is 0 ###LEFT-WALL### 14 . 1 the 2 management 2 management 3 of 2 management 10 is 3 of 6 leukemia 4 chronic 6 leukemia 5 lymphocytic 6 leukemia 6 leukemia 8 cll 7 ( 8 cll 8 cll 9 ) 10 is 11 undergoing 11 undergoing 13 changes 12 profound 13 changes several new drugs have been approved for cll treatment ( fludarabine , bendamustine , and the monoclonal antibodies alemtuzumab , rituximab , and ofatumumab ) and many more drugs are in advanced clinical development to be approved for this disease . 0 ###LEFT-WALL### 3 drugs 0 ###LEFT-WALL### 6 approved 0 ###LEFT-WALL### 12 , 0 ###LEFT-WALL### 41 . 1 several 3 drugs 2 new 3 drugs 3 drugs 4 have 4 have 5 been 5 been 6 approved 6 approved 7 for 7 for 9 treatment 8 cll 9 treatment 9 treatment 11 fludarabine 10 ( 11 fludarabine 11 fludarabine 12 , 12 , 15 and 12 , 19 alemtuzumab 12 , 20 , 13 bendamustine 15 and 14 , 15 and 15 and 18 antibodies 15 and 19 alemtuzumab 16 the 18 antibodies 17 monoclonal 18 antibodies 20 , 36 be 21 rituximab 23 and 22 , 23 and 23 and 24 ofatumumab 23 and 25 ) 23 and 26 and 26 and 29 drugs 26 and 30 are 27 many 28 more 28 more 29 drugs 30 are 31 in 30 are 35 to 31 in 34 development 32 advanced 34 development 33 clinical 34 development 35 to 36 be 36 be 37 approved 37 approved 38 for 38 for 40 disease 39 this 40 disease in addition , the extreme heterogeneity of the clinical course and our improved ability to foresee the prognosis of this leukemia by the use of clinical , biological , and genetic parameters now allow us to characterize patients with a very mild onset and course , an intermediate prognosis , or a very aggressive course with high - risk leukemia . 0 ###LEFT-WALL### 32 parameters 0 ###LEFT-WALL### 34 allow 0 ###LEFT-WALL### 61 . 1 in 11 and 1 in 32 parameters 2 addition 3 , 3 , 6 heterogeneity 3 , 11 and 4 the 6 heterogeneity 5 extreme 6 heterogeneity 6 heterogeneity 7 of 7 of 10 course 8 the 10 course 9 clinical 10 course 11 and 14 ability 11 and 15 to 11 and 25 of 12 our 14 ability 13 improved 14 ability 15 to 16 foresee 16 foresee 18 prognosis 16 foresee 22 by 17 the 18 prognosis 18 prognosis 19 of 19 of 21 leukemia 20 this 21 leukemia 22 by 24 use 23 the 24 use 24 use 25 of 26 clinical 27 , 26 clinical 32 parameters 28 biological 30 and 29 , 30 and 30 and 31 genetic 30 and 32 parameters 32 parameters 34 allow 33 now 34 allow 34 allow 35 us 34 allow 36 to 34 allow 37 characterize 36 to 37 characterize 37 characterize 38 patients 38 patients 39 with 39 with 51 or 40 a 41 very 40 a 43 onset 41 very 42 mild 42 mild 43 onset 43 onset 44 and 44 and 45 course 44 and 49 prognosis 44 and 51 or 46 , 49 prognosis 47 an 49 prognosis 48 intermediate 49 prognosis 49 prognosis 50 , 50 , 51 or 51 or 55 course 51 or 56 with 52 a 55 course 53 very 54 aggressive 54 aggressive 55 course 56 with 60 leukemia 57 high 58 - 57 high 60 leukemia 59 risk 60 leukemia therefore , it becomes [increasingly] challenging to select the right treatment strategy for each condition . 0 ###LEFT-WALL### 3 it 0 ###LEFT-WALL### 4 becomes 0 ###LEFT-WALL### 16 . 1 therefore 2 , 1 therefore 3 it 3 it 4 becomes 4 becomes 6 challenging 6 challenging 7 to 6 challenging 8 select 7 to 8 select 8 select 12 strategy 9 the 12 strategy 10 right 12 strategy 11 treatment 12 strategy 12 strategy 13 for 13 for 15 condition 14 each 15 condition this article summarizes the currently available diagnostic and therapeutic tools and gives an integrated recommendation of how to manage cll in 2013 . 0 ###LEFT-WALL### 2 article 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 23 . 1 this 2 article 2 article 11 and 3 summarizes 8 and 3 summarizes 11 and 4 the 7 diagnostic 5 currently 6 available 6 available 7 diagnostic 7 diagnostic 8 and 8 and 10 tools 9 therapeutic 10 tools 11 and 12 gives 12 gives 15 recommendation 12 gives 21 in 13 an 15 recommendation 14 integrated 15 recommendation 15 recommendation 16 of 16 of 17 how 17 how 18 to 17 how 19 manage 18 to 19 manage 19 manage 20 cll 21 in 22 2013 moreover , i propose a strategy [how] we might integrate the novel agents for cll therapy into sequential treatment approaches in the near future . 0 ###LEFT-WALL### 3 i 0 ###LEFT-WALL### 4 propose 0 ###LEFT-WALL### 25 . 1 moreover 2 , 1 moreover 3 i 3 i 4 propose 4 propose 6 strategy 4 propose 20 approaches 5 a 6 strategy 6 strategy 8 we 6 strategy 10 integrate 6 strategy 20 approaches 8 we 9 might 9 might 10 integrate 10 integrate 13 agents 10 integrate 17 into 11 the 13 agents 12 novel 13 agents 13 agents 14 for 14 for 16 therapy 15 cll 16 therapy 17 into 19 treatment 18 sequential 19 treatment 20 approaches 21 in 21 in 24 future 22 the 24 future 23 near 24 future two lingering problems regarding transplantation in older adults have been [how] to select patients appropriately and [whether] to use older sibling donors . 0 ###LEFT-WALL### 3 problems 0 ###LEFT-WALL### 23 . 1 two 3 problems 2 lingering 3 problems 3 problems 4 regarding 3 problems 16 and 4 regarding 5 transplantation 4 regarding 6 in 6 in 8 adults 7 older 8 adults 9 have 10 been 9 have 16 and 10 been 12 to 10 been 13 select 12 to 13 select 13 select 14 patients 13 select 15 appropriately 16 and 18 to 16 and 19 use 18 to 19 use 19 use 22 donors 20 older 21 sibling 21 sibling 22 donors allogeneic hematopoietic cell transplantation [(] hct [ )(of older patients may result in long - term survival due to gvl , but the data remain observational and mostly restricted to those 50 to 69 years of age . 0 ###LEFT-WALL### 6 hct 0 ###LEFT-WALL### 12 result 1 allogeneic 6 hct 2 hematopoietic 6 hct 3 cell 4 transplantation 4 transplantation 6 hct 6 hct 8 )(of 6 hct 11 may 8 )(of 10 patients 9 older 10 patients 11 may 12 result 12 result 13 in 12 result 19 to 12 result 22 but 13 in 17 survival 14 long 15 - 14 long 16 term 16 term 17 survival 18 due 19 to 19 to 20 gvl 21 , 22 but 22 but 35 years 22 but 38 . 23 the 24 data 24 data 27 and 25 remain 26 observational 25 remain 27 and 27 and 29 restricted 27 and 30 to 28 mostly 29 restricted 30 to 33 to 31 those 33 to 32 50 33 to 33 to 34 69 34 69 35 years 35 years 36 of 36 of 37 age patients with excellent performance status and low comorbidity have the best long - term survival after hct . 0 ###LEFT-WALL### 6 and 0 ###LEFT-WALL### 9 have 0 ###LEFT-WALL### 18 . 1 patients 2 with 1 patients 6 and 2 with 5 status 3 excellent 4 performance 4 performance 5 status 6 and 8 comorbidity 6 and 9 have 7 low 8 comorbidity 9 have 15 survival 9 have 16 after 10 the 11 best 10 the 15 survival 12 long 13 - 12 long 14 term 14 term 15 survival 16 after 17 hct novel measures of health status such as self [-] report or performance - based functional measures allow " staging the age " and may inform candidacy [for] less robust patients . 0 ###LEFT-WALL### 2 measures 0 ###LEFT-WALL### 23 and 0 ###LEFT-WALL### 31 . 1 novel 2 measures 2 measures 3 of 2 measures 23 and 3 of 4 health 4 health 5 status 4 health 14 based 5 status 7 as 5 status 14 based 6 such 7 as 7 as 11 or 8 self 10 report 10 report 11 or 11 or 12 performance 11 or 13 - 14 based 16 measures 15 functional 16 measures 17 allow 18 " 17 allow 19 staging 17 allow 21 age 17 allow 23 and 20 the 21 age 21 age 22 " 23 and 24 may 24 may 25 inform 25 inform 30 patients 26 candidacy 30 patients 28 less 29 robust 29 robust 30 patients older matched sibling donors should be preferred over matched unrelated donors ( muds ) because outcomes are equivalent to superior [for] matched sibling donors compared with mud . 0 ###LEFT-WALL### 4 donors 0 ###LEFT-WALL### 7 preferred 0 ###LEFT-WALL### 28 . 1 older 3 sibling 2 matched 3 sibling 3 sibling 4 donors 4 donors 5 should 5 should 6 be 6 be 7 preferred 7 preferred 8 over 7 preferred 15 because 8 over 11 donors 9 matched 11 donors 10 unrelated 11 donors 11 donors 13 muds 12 ( 13 muds 13 muds 14 ) 15 because 16 outcomes 15 because 17 are 16 outcomes 17 are 17 are 18 equivalent 18 equivalent 19 to 19 to 24 donors 20 superior 24 donors 22 matched 23 sibling 23 sibling 24 donors 24 donors 25 compared 24 donors 26 with 26 with 27 mud however , muds also achieve acceptable outcomes and long - term disease control . 0 ###LEFT-WALL### 3 muds 0 ###LEFT-WALL### 5 achieve 0 ###LEFT-WALL### 14 . 1 however 2 , 1 however 3 muds 3 muds 5 achieve 4 also 5 achieve 5 achieve 8 and 6 acceptable 7 outcomes 7 outcomes 8 and 8 and 13 control 9 long 10 - 9 long 11 term 11 term 13 control 12 disease 13 control an alternative donor can be considered [based] on institutional protocols and expertise . 0 ###LEFT-WALL### 3 donor 0 ###LEFT-WALL### 6 considered 0 ###LEFT-WALL### 13 . 1 an 2 alternative 1 an 3 donor 2 alternative 3 donor 3 donor 4 can 4 can 5 be 5 be 6 considered 6 considered 8 on 8 on 11 and 9 institutional 10 protocols 10 protocols 11 and 11 and 12 expertise very limited information is available in patients or related donors 70 years of age and older . 0 ###LEFT-WALL### 3 information 0 ###LEFT-WALL### 8 or 0 ###LEFT-WALL### 17 . 1 very 2 limited 2 limited 3 information 3 information 8 or 4 is 5 available 4 is 8 or 5 available 6 in 6 in 7 patients 8 or 9 related 8 or 15 and 9 related 10 donors 11 70 12 years 12 years 13 of 12 years 15 and 13 of 14 age 15 and 16 older future efforts to more completely characterize patient health status before transplantation will allow better application of hct in older adults . 0 ###LEFT-WALL### 2 efforts 0 ###LEFT-WALL### 13 allow 0 ###LEFT-WALL### 21 . 1 future 2 efforts 2 efforts 3 to 2 efforts 6 characterize 2 efforts 12 will 3 to 6 characterize 4 more 5 completely 5 completely 6 characterize 6 characterize 9 status 6 characterize 10 before 7 patient 8 health 8 health 9 status 10 before 11 transplantation 12 will 13 allow 13 allow 15 application 13 allow 18 in 14 better 15 application 15 application 16 of 16 of 17 hct 18 in 20 adults 19 older 20 adults hemophilia is caused by a functional deficiency of one of the coagulation proteins . 0 ###LEFT-WALL### 1 hemophilia 0 ###LEFT-WALL### 3 caused 0 ###LEFT-WALL### 14 . 1 hemophilia 2 is 2 is 3 caused 3 caused 4 by 4 by 7 deficiency 5 a 6 functional 5 a 7 deficiency 6 functional 7 deficiency 7 deficiency 8 of 8 of 9 one 9 one 10 of 10 of 13 proteins 11 the 13 proteins 12 coagulation 13 proteins therapy for no other group of genetic diseases has seen the progress that has been made for hemophilia over the past 40 years , from a life expectancy in 1970 of ∼20 years for a boy born with severe hemophilia to [essentially] a normal life expectancy in 2013 with current prophylaxis therapy . 0 ###LEFT-WALL### 1 therapy 0 ###LEFT-WALL### 10 seen 1 therapy 2 for 1 therapy 6 of 1 therapy 9 has 2 for 5 group 3 no 4 other 4 other 5 group 6 of 8 diseases 7 genetic 8 diseases 9 has 10 seen 10 seen 12 progress 10 seen 17 for 11 the 12 progress 12 progress 13 that 12 progress 14 has 13 that 14 has 14 has 15 been 15 been 16 made 17 for 18 hemophilia 18 hemophilia 19 over 18 hemophilia 25 from 19 over 23 years 20 the 21 past 20 the 23 years 22 40 23 years 24 , 25 from 25 from 28 expectancy 25 from 53 . 26 a 27 life 26 a 28 expectancy 27 life 28 expectancy 28 expectancy 29 in 29 in 30 1970 30 1970 31 of 30 1970 34 for 31 of 33 years 32 ∼20 33 years 34 for 36 boy 35 a 36 boy 36 boy 37 born 37 born 38 with 37 born 41 to 37 born 49 with 38 with 40 hemophilia 39 severe 40 hemophilia 41 to 46 expectancy 43 a 46 expectancy 44 normal 45 life 45 life 46 expectancy 46 expectancy 47 in 47 in 48 2013 49 with 52 therapy 50 current 51 prophylaxis 51 prophylaxis 52 therapy however , these therapies are expensive and [require] iv infusions 3 to 4 times each week . 0 ###LEFT-WALL### 4 therapies 0 ###LEFT-WALL### 5 are 0 ###LEFT-WALL### 17 . 1 however 2 , 1 however 4 therapies 3 these 4 therapies 4 therapies 5 are 5 are 7 and 5 are 14 times 5 are 16 week 6 expensive 7 and 7 and 10 infusions 9 iv 10 infusions 10 infusions 12 to 11 3 12 to 12 to 13 4 13 4 14 times 15 each 16 week these are exciting times for hemophilia because several new technologies that promise extended half - lives for factor products , with potential for improvements in quality of life for persons with hemophilia , are in late - phase clinical development . 0 ###LEFT-WALL### 1 these 0 ###LEFT-WALL### 2 are 0 ###LEFT-WALL### 41 . 1 these 2 are 2 are 4 times 3 exciting 4 times 4 times 5 for 4 times 16 lives 4 times 34 are 5 for 6 hemophilia 7 because 10 technologies 7 because 13 extended 7 because 15 - 7 because 16 lives 8 several 10 technologies 9 new 10 technologies 10 technologies 11 that 10 technologies 12 promise 10 technologies 13 extended 11 that 12 promise 13 extended 14 half 16 lives 17 for 16 lives 34 are 17 for 19 products 18 factor 19 products 19 products 21 with 20 , 21 with 21 with 22 potential 21 with 23 for 21 with 33 , 23 for 24 improvements 24 improvements 25 in 24 improvements 27 of 25 in 26 quality 27 of 28 life 28 life 29 for 29 for 30 persons 30 persons 31 with 31 with 32 hemophilia 34 are 35 in 35 in 40 development 36 late 37 - 36 late 38 phase 38 phase 40 development 39 clinical 40 development objectives : in the present study , we developed new software for quantitative analysis of cervical vertebrae maturation , and we evaluated its applicability through a multinomial logistic regression model ( mlrm ) . 0 ###LEFT-WALL### 1 objectives 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 7 , 0 ###LEFT-WALL### 34 . 1 objectives 2 : 2 : 3 in 3 in 6 study 4 the 6 study 5 present 6 study 7 , 8 we 7 , 9 developed 7 , 20 and 8 we 9 developed 9 developed 11 software 10 new 11 software 11 software 12 for 11 software 15 of 12 for 14 analysis 13 quantitative 14 analysis 15 of 18 maturation 16 cervical 17 vertebrae 17 vertebrae 18 maturation 19 , 20 and 20 and 21 we 20 and 22 evaluated 21 we 22 evaluated 22 evaluated 24 applicability 22 evaluated 25 through 23 its 24 applicability 25 through 30 model 26 a 27 multinomial 26 a 30 model 27 multinomial 28 logistic 28 logistic 29 regression 29 regression 30 model 30 model 32 mlrm 31 ( 32 mlrm 32 mlrm 33 ) methods : digitized images of the bodies of the second ( c2 ) , third ( c3 ) [and] fourth ( c4 ) cervical vertebrae were analysed in cephalometric [radiographs] [of] 236 subjects ( 116 boys and 120 girls ) by using [a] software developed for digitized vertebrae analysis . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 4 images 2 : 14 , 3 digitized 4 images 4 images 5 of 4 images 8 of 5 of 7 bodies 6 the 7 bodies 8 of 10 second 9 the 10 second 10 second 12 c2 11 ( 12 c2 12 c2 13 ) 14 , 25 vertebrae 15 third 25 vertebrae 16 ( 17 c3 17 c3 18 ) 17 c3 25 vertebrae 20 fourth 25 vertebrae 21 ( 22 c4 22 c4 23 ) 22 c4 25 vertebrae 24 cervical 25 vertebrae 25 vertebrae 26 were 26 were 27 analysed 27 analysed 28 in 28 in 33 subjects 29 cephalometric 33 subjects 32 236 33 subjects 33 subjects 44 software 34 ( 44 software 35 116 36 boys 36 boys 37 and 37 and 39 girls 37 and 40 ) 37 and 41 by 37 and 44 software 38 120 39 girls 41 by 42 using 44 software 45 developed 44 software 50 . 45 developed 46 for 46 for 49 analysis 47 digitized 48 vertebrae 48 vertebrae 49 analysis the sample was initially distributed into 11 categories according to the fishman 's skeletal maturity indicators and were then grouped into four stages for quantitative cervical maturational [changes] ( qcmc ) analysis ( qcmc i , ii , [iii] and iv ) . 0 ###LEFT-WALL### 2 sample 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 43 . 1 the 2 sample 2 sample 17 and 3 was 5 distributed 3 was 17 and 4 initially 5 distributed 5 distributed 6 into 5 distributed 10 to 6 into 8 categories 7 11 8 categories 9 according 10 to 10 to 16 indicators 11 the 12 fishman 12 fishman 13 's 13 's 16 indicators 14 skeletal 15 maturity 15 maturity 16 indicators 17 and 18 were 17 and 40 and 18 were 20 grouped 19 then 20 grouped 20 grouped 21 into 21 into 22 four 23 stages 24 for 23 stages 40 and 24 for 32 analysis 25 quantitative 32 analysis 26 cervical 32 analysis 27 maturational 30 qcmc 27 maturational 32 analysis 29 ( 30 qcmc 30 qcmc 31 ) 32 analysis 34 qcmc 32 analysis 37 ii 33 ( 34 qcmc 34 qcmc 35 i 34 qcmc 36 , 36 , 37 ii 37 ii 38 , 38 , 40 and 40 and 41 iv 40 and 42 ) seven variables of interest were measured and analysed to identify morphologic alterations of the vertebral bodies in each qcmc category . 0 ###LEFT-WALL### 2 variables 0 ###LEFT-WALL### 7 and 0 ###LEFT-WALL### 21 . 1 seven 2 variables 2 variables 3 of 2 variables 7 and 3 of 4 interest 5 were 6 measured 5 were 7 and 7 and 8 analysed 7 and 9 to 9 to 10 identify 10 identify 12 alterations 10 identify 17 in 11 morphologic 12 alterations 12 alterations 13 of 13 of 16 bodies 14 the 16 bodies 15 vertebral 16 bodies 17 in 20 category 18 each 20 category 19 qcmc 20 category results : statistically significant differences ( p < 0.05 ) were observed among all qcmc categories for the variables analysed . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 5 differences 2 : 12 observed 2 : 21 . 3 statistically 4 significant 4 significant 5 differences 5 differences 8 < 5 differences 11 were 6 ( 8 < 7 p 8 < 8 < 9 0.05 8 < 10 ) 11 were 12 observed 12 observed 13 among 13 among 16 categories 14 all 16 categories 15 qcmc 16 categories 16 categories 17 for 17 for 19 variables 18 the 19 variables 19 variables 20 analysed the mlrm used to calculate the probability that an individual belonged to each of the four cervical vertebrae maturation categories was constructed by taking into account gender , chronological age and four variables determined by digitized vertebrae analysis ( ang_c3 , mp_c3 , mp_c4 and sp_c4 ) . 0 ###LEFT-WALL### 2 mlrm 0 ###LEFT-WALL### 22 constructed 0 ###LEFT-WALL### 34 determined 0 ###LEFT-WALL### 48 . 1 the 2 mlrm 2 mlrm 3 used 2 mlrm 4 to 2 mlrm 5 calculate 2 mlrm 21 was 4 to 5 calculate 5 calculate 7 probability 5 calculate 12 to 6 the 7 probability 7 probability 8 that 8 that 10 individual 8 that 11 belonged 9 an 10 individual 10 individual 11 belonged 12 to 20 categories 13 each 14 of 13 each 20 categories 14 of 20 categories 15 the 16 four 16 four 20 categories 17 cervical 20 categories 18 vertebrae 20 categories 19 maturation 20 categories 21 was 22 constructed 22 constructed 23 by 22 constructed 28 , 22 constructed 29 chronological 23 by 24 taking 24 taking 25 into 25 into 27 gender 26 account 27 gender 30 age 31 and 31 and 33 variables 31 and 34 determined 32 four 33 variables 34 determined 35 by 35 by 38 analysis 36 digitized 37 vertebrae 37 vertebrae 38 analysis 38 analysis 45 and 39 ( 45 and 40 ang_c3 41 , 41 , 42 mp_c3 41 , 43 , 43 , 44 mp_c4 43 , 45 and 45 and 46 sp_c4 45 and 47 ) the mlrm presented a predictability of 81.4 % . 0 ###LEFT-WALL### 2 mlrm 0 ###LEFT-WALL### 3 presented 0 ###LEFT-WALL### 9 . 1 the 2 mlrm 2 mlrm 3 presented 3 presented 5 predictability 4 a 5 predictability 5 predictability 6 of 6 of 8 % 7 81.4 8 % the weighted κ test showed almost perfect agreement ( κ [=] 0.832 ) between the categories defined initially by the method of fishman and those allocated by the mlrm . 0 ###LEFT-WALL### 4 test 0 ###LEFT-WALL### 5 showed 0 ###LEFT-WALL### 30 . 1 the 4 test 2 weighted 4 test 3 κ 4 test 4 test 5 showed 5 showed 8 agreement 5 showed 14 between 5 showed 19 by 6 almost 7 perfect 7 perfect 8 agreement 8 agreement 10 κ 9 ( 10 κ 10 κ 12 0.832 10 κ 13 ) 14 between 16 categories 15 the 16 categories 16 categories 17 defined 17 defined 18 initially 19 by 24 and 20 the 21 method 21 method 22 of 21 method 24 and 22 of 23 fishman 24 and 25 those 24 and 26 allocated 26 allocated 27 by 27 by 29 mlrm 28 the 29 mlrm conclusions : significant alterations in the morphologies of the c2 , c3 and c4 vertebral bodies that were analysed through the digitized vertebrae analysis software occur during the different stages of skeletal maturation . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 13 and 2 : 26 occur 2 : 34 . 3 significant 4 alterations 4 alterations 5 in 4 alterations 11 , 5 in 7 morphologies 6 the 7 morphologies 7 morphologies 8 of 8 of 10 c2 9 the 10 c2 11 , 12 c3 11 , 13 and 13 and 16 bodies 13 and 17 that 13 and 18 were 13 and 26 occur 14 c4 16 bodies 15 vertebral 16 bodies 17 that 18 were 18 were 19 analysed 19 analysed 20 through 20 through 25 software 21 the 25 software 22 digitized 23 vertebrae 23 vertebrae 24 analysis 24 analysis 25 software 26 occur 27 during 27 during 30 stages 28 the 30 stages 29 different 30 stages 30 stages 31 of 31 of 33 maturation 32 skeletal 33 maturation the model that combines the four parameters measured on the vertebral bodies , the age and the gender showed an excellent prediction . 0 ###LEFT-WALL### 2 model 0 ###LEFT-WALL### 19 showed 0 ###LEFT-WALL### 23 . 1 the 2 model 2 model 3 that 2 model 4 combines 2 model 19 showed 3 that 4 combines 4 combines 7 parameters 5 the 6 four 6 four 7 parameters 7 parameters 8 measured 8 measured 9 on 9 on 16 and 10 the 12 bodies 11 vertebral 12 bodies 12 bodies 13 , 13 , 15 age 13 , 16 and 14 the 15 age 16 and 18 gender 17 the 18 gender 19 showed 22 prediction 20 an 21 excellent 20 an 22 prediction 21 excellent 22 prediction the rapidly aging population and their frequent use of hospital services will create substantial quality challenges in the near future . 0 ###LEFT-WALL### 5 and 0 ###LEFT-WALL### 13 create 0 ###LEFT-WALL### 21 . 1 the 4 population 2 rapidly 3 aging 3 aging 4 population 4 population 5 and 5 and 8 use 5 and 9 of 5 and 12 will 6 their 8 use 7 frequent 8 use 9 of 11 services 10 hospital 11 services 12 will 13 create 13 create 16 challenges 13 create 17 in 14 substantial 15 quality 15 quality 16 challenges 17 in 20 future 18 the 20 future 19 near 20 future redesigning rural hospital work environments is the key to improving the quality of care for older adults . 0 ###LEFT-WALL### 1 redesigning 0 ###LEFT-WALL### 6 is 0 ###LEFT-WALL### 18 . 1 redesigning 5 environments 1 redesigning 6 is 2 rural 3 hospital 3 hospital 5 environments 4 work 5 environments 6 is 8 key 7 the 8 key 8 key 9 to 9 to 10 improving 10 improving 12 quality 11 the 12 quality 12 quality 13 of 13 of 14 care 14 care 15 for 15 for 17 adults 16 older 17 adults this study explored [how] the work environment influences registered nurses ' ( rns ' ) perceived quality of geriatric care in rural hospitals . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 16 perceived 0 ###LEFT-WALL### 24 . 1 this 2 study 2 study 3 explored 2 study 7 environment 2 study 8 influences 2 study 14 ' 2 study 16 perceived 5 the 7 environment 6 work 7 environment 7 environment 8 influences 8 influences 11 ' 9 registered 10 nurses 10 nurses 11 ' 12 ( 14 ' 13 rns 14 ' 14 ' 15 ) 16 perceived 17 quality 16 perceived 21 in 17 quality 18 of 18 of 20 care 19 geriatric 20 care 21 in 23 hospitals 22 rural 23 hospitals we used an exploratory [mixed] - methods research design emphasizing the qualitative data ( in [-] depth , semi - structured interviews ) . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 used 0 ###LEFT-WALL### 24 . 1 we 2 used 2 used 9 design 2 used 15 in 3 an 4 exploratory 3 an 9 design 4 exploratory 6 - 4 exploratory 7 methods 7 methods 9 design 8 research 9 design 9 design 10 emphasizing 10 emphasizing 13 data 11 the 13 data 12 qualitative 13 data 14 ( 15 in 15 in 17 depth 15 in 23 ) 17 depth 22 interviews 18 , 22 interviews 19 semi 20 - 19 semi 22 interviews 21 structured 22 interviews 22 interviews 23 ) quantitative data [(] [questionnaire] [ )(measuring the [rn] work environment were also collected to augment qualitative data . 0 ###LEFT-WALL### 2 data 0 ###LEFT-WALL### 11 were 0 ###LEFT-WALL### 18 . 1 quantitative 2 data 2 data 6 )(measuring 2 data 11 were 6 )(measuring 10 environment 7 the 10 environment 9 work 10 environment 11 were 12 also 11 were 13 collected 13 collected 14 to 13 collected 15 augment 14 to 15 augment 15 augment 17 data 16 qualitative 17 data four themes emerged : [(] [a] [ )(collegial [rn] relationships , [(] [b] [ )(poor staffing/utilization , [(] [c] [ )(technology benefits/challenges , [and] [(] d [ )( - physician interactions , which were identified as key factors influencing the quality of geriatric care . 0 ###LEFT-WALL### 2 themes 0 ###LEFT-WALL### 3 emerged 0 ###LEFT-WALL### 4 : 1 four 2 themes 2 themes 3 emerged 4 : 10 relationships 4 : 11 , 8 )(collegial 10 relationships 11 , 16 staffing/utilization 11 , 17 , 15 )(poor 16 staffing/utilization 17 , 21 )(technology 17 , 22 benefits/challenges 21 )(technology 22 benefits/challenges 22 benefits/challenges 29 - 23 , 29 - 26 d 29 - 29 - 31 interactions 30 physician 31 interactions 31 interactions 33 which 32 , 33 which 33 which 34 were 33 which 45 . 34 were 35 identified 35 identified 36 as 36 as 38 factors 37 key 38 factors 38 factors 39 influencing 39 influencing 41 quality 40 the 41 quality 41 quality 42 of 42 of 44 care 43 geriatric 44 care we concluded that rural hospital work environments may not be optimized to facilitate the delivery of quality geriatric care . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 concluded 0 ###LEFT-WALL### 20 . 1 we 2 concluded 2 concluded 3 that 3 that 7 environments 3 that 11 optimized 4 rural 5 hospital 5 hospital 7 environments 6 work 7 environments 7 environments 8 may 8 may 9 not 8 may 10 be 10 be 11 optimized 11 optimized 12 to 12 to 13 facilitate 13 facilitate 15 delivery 14 the 15 delivery 15 delivery 16 of 16 of 19 care 17 quality 19 care 18 geriatric 19 care targeted interventions are needed to improve overall quality of care for hospitalized older adults in rural settings . 0 ###LEFT-WALL### 2 interventions 0 ###LEFT-WALL### 4 needed 0 ###LEFT-WALL### 18 . 1 targeted 2 interventions 2 interventions 3 are 3 are 4 needed 4 needed 5 to 5 to 6 improve 6 improve 8 quality 6 improve 15 in 7 overall 8 quality 8 quality 9 of 9 of 10 care 10 care 11 for 11 for 14 adults 12 hospitalized 14 adults 13 older 14 adults 15 in 17 settings 16 rural 17 settings alterations in the circulating cd8+ [t] cell pool , with a loss of naïve and accumulation of effector/effector memory cells , are pronounced in older adults . 0 ###LEFT-WALL### 1 alterations 0 ###LEFT-WALL### 23 pronounced 0 ###LEFT-WALL### 27 . 1 alterations 2 in 1 alterations 22 are 2 in 8 pool 3 the 8 pool 4 circulating 7 cell 5 cd8+ 7 cell 7 cell 8 pool 8 pool 10 with 9 , 10 with 10 with 12 loss 10 with 21 , 11 a 12 loss 12 loss 13 of 12 loss 17 of 13 of 15 and 14 naïve 15 and 15 and 16 accumulation 17 of 20 cells 18 effector/effector 20 cells 19 memory 20 cells 22 are 23 pronounced 23 pronounced 24 in 24 in 26 adults 25 older 26 adults however , homeostatic forces that dictate such changes remain incompletely understood . 0 ###LEFT-WALL### 4 forces 0 ###LEFT-WALL### 9 remain 0 ###LEFT-WALL### 12 . 1 however 2 , 1 however 4 forces 3 homeostatic 4 forces 4 forces 5 that 4 forces 6 dictate 4 forces 9 remain 5 that 6 dictate 6 dictate 8 changes 7 such 8 changes 9 remain 11 understood 10 incompletely 11 understood this observational cross - sectional study explored the basis for variability of cd8+ [t] cell number and composition of its main subsets : naïve , central memory and effector memory t cells , in 131 cytomegalovirus ( cmv ) seropositive subjects aged over 60 years . 0 ###LEFT-WALL### 3 cross 0 ###LEFT-WALL### 4 - 0 ###LEFT-WALL### 46 . 1 this 2 observational 2 observational 3 cross 4 - 6 study 4 - 7 explored 4 - 23 : 4 - 33 , 5 sectional 6 study 6 study 7 explored 7 explored 9 basis 7 explored 10 for 8 the 9 basis 10 for 11 variability 11 variability 12 of 11 variability 19 of 12 of 17 and 13 cd8+ 16 number 15 cell 16 number 16 number 17 and 17 and 18 composition 19 of 22 subsets 20 its 21 main 20 its 22 subsets 23 : 28 and 24 naïve 25 , 24 naïve 27 memory 26 central 27 memory 27 memory 28 and 28 and 32 cells 29 effector 32 cells 30 memory 31 t 30 memory 32 cells 33 , 41 subjects 33 , 42 aged 34 in 36 cytomegalovirus 34 in 39 ) 34 in 41 subjects 35 131 36 cytomegalovirus 36 cytomegalovirus 38 cmv 37 ( 38 cmv 38 cmv 39 ) 40 seropositive 41 subjects 41 subjects 42 aged 42 aged 43 over 43 over 45 years 44 60 45 years we found great heterogeneity of cd8+ t cell numbers , which was mainly due to variability of the cd8 [+] cd28 [-] t cell subset regardless of age . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 found 0 ###LEFT-WALL### 10 , 0 ###LEFT-WALL### 29 . 1 we 2 found 2 found 4 heterogeneity 2 found 9 numbers 3 great 4 heterogeneity 4 heterogeneity 5 of 5 of 6 cd8+ 6 cd8+ 7 t 8 cell 9 numbers 10 , 11 which 10 , 12 was 11 which 12 was 12 was 13 mainly 12 was 15 to 12 was 27 of 14 due 15 to 15 to 16 variability 16 variability 17 of 17 of 25 subset 18 the 25 subset 19 cd8 21 cd28 21 cd28 23 t 21 cd28 25 subset 24 cell 25 subset 26 regardless 27 of 27 of 28 age analysis , by multiple regression , of distinct factors revealed that age was a predictor for the loss in absolute number [of] naïve [t] cells , but was not associated with changes in central or effector memory cd8+ t cell subsets . 0 ###LEFT-WALL### 1 analysis 0 ###LEFT-WALL### 2 , 0 ###LEFT-WALL### 42 . 2 , 12 age 2 , 27 but 3 by 5 regression 3 by 6 , 3 by 12 age 4 multiple 5 regression 7 of 9 factors 7 of 12 age 8 distinct 9 factors 9 factors 10 revealed 11 that 12 age 12 age 27 but 13 was 15 predictor 13 was 27 but 14 a 15 predictor 15 predictor 16 for 15 predictor 19 in 16 for 18 loss 17 the 18 loss 19 in 25 cells 20 absolute 21 number 21 number 25 cells 23 naïve 25 cells 26 , 27 but 27 but 28 was 28 was 29 not 28 was 31 with 28 was 33 in 29 not 30 associated 31 with 32 changes 33 in 41 subsets 34 central 35 or 35 or 38 cd8+ 35 or 40 cell 36 effector 38 cd8+ 37 memory 38 cd8+ 38 cd8+ 39 t 40 cell 41 subsets [by] contrast , the size of cd8+ [t] cells specific to pp65 and ie - 1 antigens of cmv , predicted cd28 - cd8+ t cell , antigen - experienced cd8+ t cell , and even total cd8+ t cell numbers , but not naïve cd8+ t cell loss . 0 ###LEFT-WALL### 2 contrast 0 ###LEFT-WALL### 3 , 3 , 13 and 4 the 5 size 5 size 6 of 5 size 10 specific 5 size 13 and 6 of 9 cells 7 cd8+ 9 cells 10 specific 11 to 11 to 12 pp65 13 and 14 ie 13 and 17 antigens 13 and 23 - 15 - 17 antigens 16 1 17 antigens 17 antigens 18 of 17 antigens 20 , 18 of 19 cmv 20 , 23 - 21 predicted 22 cd28 22 cd28 23 - 23 - 24 cd8+ 24 cd8+ 25 t 24 cd8+ 26 cell 24 cd8+ 30 experienced 26 cell 28 antigen 26 cell 30 experienced 27 , 28 antigen 28 antigen 29 - 30 experienced 31 cd8+ 31 cd8+ 32 t 31 cd8+ 40 cell 31 cd8+ 41 numbers 33 cell 35 and 34 , 35 and 35 and 38 cd8+ 35 and 40 cell 36 even 37 total 37 total 38 cd8+ 38 cd8+ 39 t 40 cell 41 numbers 41 numbers 43 but 42 , 43 but 43 but 44 not 43 but 49 loss 43 but 50 . 44 not 45 naïve 45 naïve 46 cd8+ 46 cd8+ 47 t 48 cell 49 loss these results indicate a clear dichotomy between the homeostasis of naïve and antigen - experienced subsets of cd8+ t cells which are independently affected , in human later life , by age and antigen - specific responses to cmv , respectively . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 indicate 0 ###LEFT-WALL### 14 - 0 ###LEFT-WALL### 42 . 1 these 2 results 2 results 3 indicate 3 indicate 6 dichotomy 3 indicate 7 between 4 a 5 clear 4 a 6 dichotomy 5 clear 6 dichotomy 7 between 9 homeostasis 8 the 9 homeostasis 9 homeostasis 10 of 10 of 12 and 11 naïve 12 and 12 and 13 antigen 14 - 16 subsets 15 experienced 16 subsets 16 subsets 17 of 17 of 18 cd8+ 18 cd8+ 19 t 18 cd8+ 20 cells 18 cd8+ 24 affected 20 cells 21 which 20 cells 22 are 20 cells 24 affected 21 which 22 are 23 independently 24 affected 24 affected 26 in 24 affected 31 by 24 affected 41 respectively 25 , 26 in 26 in 29 life 26 in 30 , 27 human 29 life 28 later 29 life 30 , 31 by 31 by 33 and 31 by 40 , 32 age 33 and 33 and 37 responses 33 and 38 to 34 antigen 35 - 34 antigen 37 responses 36 specific 37 responses 38 to 39 cmv purpose of the study : older americans contemplating retirement today face a very different economic environment than prior cohorts did . 0 ###LEFT-WALL### 4 study 0 ###LEFT-WALL### 5 : 0 ###LEFT-WALL### 21 . 1 purpose 2 of 2 of 3 the 3 the 4 study 5 : 7 americans 5 : 11 face 6 older 7 americans 7 americans 8 contemplating 7 americans 11 face 8 contemplating 9 retirement 8 contemplating 10 today 11 face 16 environment 11 face 17 than 12 a 13 very 12 a 16 environment 13 very 14 different 14 different 16 environment 15 economic 16 environment 17 than 20 did 18 prior 19 cohorts 19 cohorts 20 did this article examines whether the retirement patterns of older americans have changed as a result . 0 ###LEFT-WALL### 2 article 0 ###LEFT-WALL### 3 examines 0 ###LEFT-WALL### 16 . 1 this 2 article 2 article 3 examines 3 examines 4 whether 4 whether 7 patterns 4 whether 12 changed 5 the 7 patterns 6 retirement 7 patterns 7 patterns 8 of 7 patterns 11 have 8 of 10 americans 9 older 10 americans 11 have 12 changed 12 changed 13 as 13 as 15 result 14 a 15 result design and methods : using data from 10 waves of the health and retirement study ( hrs ) , we examine the prevalence of bridge jobs , phased retirement , and labor market reentry among 3 recent cohorts of older americans , from 1992 through 2010 . 0 ###LEFT-WALL### 3 methods 0 ###LEFT-WALL### 4 : 0 ###LEFT-WALL### 19 , 1 design 2 and 2 and 3 methods 3 methods 4 : 4 : 5 using 5 using 6 data 5 using 7 from 7 from 9 waves 8 10 9 waves 9 waves 10 of 10 of 13 and 11 the 12 health 12 health 13 and 13 and 17 hrs 13 and 18 ) 14 retirement 15 study 15 study 17 hrs 16 ( 17 hrs 17 hrs 18 ) 19 , 20 we 19 , 21 examine 20 we 21 examine 21 examine 31 and 21 examine 33 market 22 the 23 prevalence 23 prevalence 24 of 23 prevalence 27 , 24 of 26 jobs 25 bridge 26 jobs 27 , 29 retirement 27 , 31 and 28 phased 29 retirement 30 , 31 and 31 and 32 labor 31 and 33 market 33 market 34 reentry 33 market 35 among 33 market 43 from 35 among 38 cohorts 36 3 38 cohorts 37 recent 38 cohorts 38 cohorts 39 of 39 of 41 americans 40 older 41 americans 42 , 43 from 43 from 44 1992 43 from 47 . 44 1992 45 through 45 through 46 2010 determinants of retirement transitions are examined using bivariate comparisons and multivariate logistic and multinomial logistic regression models . 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 18 . 1 determinants 2 of 1 determinants 6 examined 1 determinants 10 and 2 of 3 retirement 3 retirement 4 transitions 3 retirement 5 are 4 transitions 5 are 6 examined 7 using 7 using 9 comparisons 8 bivariate 9 comparisons 10 and 17 models 11 multivariate 17 models 12 logistic 13 and 13 and 14 multinomial 13 and 17 models 15 logistic 17 models 16 regression 17 models results : we find that traditional one - time , permanent exits from the labor force continue to be the exception rather than the rule and that the retirement patterns of the early boomers , those on the cusp of retirement during the recent great recession , appear to be diverging from those of earlier cohorts . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 50 be 0 ###LEFT-WALL### 57 . 2 : 3 we 2 : 4 find 2 : 10 , 2 : 47 , 3 we 4 find 4 find 7 one 5 that 7 one 6 traditional 7 one 7 one 9 time 8 - 9 time 9 time 10 , 10 , 12 exits 10 , 17 continue 11 permanent 12 exits 12 exits 13 from 12 exits 17 continue 13 from 16 force 14 the 16 force 15 labor 16 force 17 continue 18 to 17 continue 19 be 18 to 19 be 19 be 21 exception 19 be 23 than 20 the 21 exception 22 rather 23 than 23 than 26 and 24 the 25 rule 25 rule 26 and 26 and 27 that 26 and 29 retirement 26 and 30 patterns 26 and 31 of 28 the 29 retirement 29 retirement 30 patterns 31 of 34 boomers 32 the 34 boomers 33 early 34 boomers 34 boomers 36 those 35 , 36 those 36 those 37 on 36 those 40 of 36 those 47 , 37 on 39 cusp 38 the 39 cusp 40 of 41 retirement 41 retirement 42 during 42 during 46 recession 43 the 46 recession 44 recent 46 recession 45 great 46 recession 47 , 48 appear 48 appear 49 to 49 to 50 be 50 be 51 diverging 51 diverging 52 from 52 from 53 those 53 those 54 of 54 of 56 cohorts 55 earlier 56 cohorts the early boomer women , in particular , were more likely than those in previous cohorts , the hrs core and the hrs war babies , to move to a bridge job prior to exiting the labor force completely and both early boomer men and women were more likely to leave their career jobs involuntarily , with layoffs being a key factor . 0 ###LEFT-WALL### 4 women 0 ###LEFT-WALL### 9 were 0 ###LEFT-WALL### 63 . 1 the 4 women 2 early 4 women 3 boomer 4 women 4 women 7 particular 4 women 9 were 5 , 7 particular 6 in 7 particular 7 particular 8 , 9 were 10 more 9 were 11 likely 11 likely 12 than 11 likely 14 in 11 likely 27 to 11 likely 57 with 12 than 13 those 14 in 21 and 15 previous 16 cohorts 16 cohorts 17 , 17 , 20 core 17 , 21 and 18 the 20 core 19 hrs 20 core 21 and 25 babies 22 the 25 babies 23 hrs 24 war 24 war 25 babies 26 , 27 to 27 to 40 and 27 to 56 , 28 move 29 to 28 move 34 to 28 move 40 and 29 to 32 job 30 a 32 job 31 bridge 32 job 33 prior 34 to 34 to 35 exiting 35 exiting 38 force 35 exiting 39 completely 36 the 38 force 37 labor 38 force 40 and 51 leave 41 both 44 men 42 early 43 boomer 43 boomer 44 men 44 men 45 and 45 and 46 women 45 and 47 were 47 were 49 likely 48 more 49 likely 49 likely 50 to 50 to 51 leave 51 leave 54 jobs 51 leave 55 involuntarily 52 their 54 jobs 53 career 54 jobs 57 with 58 layoffs 58 layoffs 59 being 59 being 62 factor 60 a 62 factor 61 key 62 factor implications : the " do - it - yourself " approach to retirement planning - with individuals managing a large portion of their retirement finances - is now common among older americans . 0 ###LEFT-WALL### 1 implications 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 6 - 1 implications 2 : 2 : 5 do 3 the 4 " 3 the 5 do 6 - 7 it 6 - 8 - 8 - 11 approach 8 - 33 . 9 yourself 10 " 9 yourself 11 approach 11 approach 12 to 12 to 13 retirement 13 retirement 14 planning 13 retirement 27 is 13 retirement 29 common 14 planning 16 with 14 planning 27 is 15 - 16 with 16 with 17 individuals 16 with 26 - 17 individuals 18 managing 18 managing 21 portion 19 a 21 portion 20 large 21 portion 21 portion 22 of 22 of 25 finances 23 their 25 finances 24 retirement 25 finances 27 is 28 now 29 common 30 among 30 among 32 americans 31 older 32 americans this change in the retirement environment , combined with a significant and persistent cyclical downturn , may have long - lasting effects and suggests that the concept of retirement in the united states will continue to evolve . 0 ###LEFT-WALL### 2 change 0 ###LEFT-WALL### 23 and 0 ###LEFT-WALL### 38 . 1 this 2 change 2 change 3 in 2 change 17 may 3 in 6 environment 4 the 6 environment 5 retirement 6 environment 6 environment 8 combined 7 , 8 combined 8 combined 9 with 8 combined 16 , 9 with 15 downturn 10 a 15 downturn 11 significant 12 and 12 and 13 persistent 12 and 15 downturn 14 cyclical 15 downturn 17 may 23 and 18 have 22 effects 18 have 23 and 19 long 20 - 19 long 22 effects 21 lasting 22 effects 23 and 24 suggests 24 suggests 25 that 25 that 27 concept 25 that 35 continue 26 the 27 concept 27 concept 28 of 27 concept 30 in 27 concept 34 will 28 of 29 retirement 30 in 33 states 31 the 33 states 32 united 33 states 34 will 35 continue 35 continue 36 to 35 continue 37 evolve 36 to 37 evolve background : there is increasing need for rehabilitation in both cancer and palliative care . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 3 there 2 : 4 is 2 : 15 . 3 there 4 is 4 is 6 need 5 increasing 6 need 6 need 7 for 7 for 8 rehabilitation 8 rehabilitation 9 in 9 in 12 and 10 both 12 and 11 cancer 12 and 12 and 14 care 13 palliative 14 care however , there are few validated outcome measures that are suitable for measuring functional performance in this population . 0 ###LEFT-WALL### 3 there 0 ###LEFT-WALL### 4 are 0 ###LEFT-WALL### 19 . 1 however 2 , 1 however 3 there 3 there 4 are 4 are 8 measures 5 few 8 measures 6 validated 7 outcome 7 outcome 8 measures 8 measures 9 that 8 measures 10 are 9 that 10 are 10 are 11 suitable 11 suitable 12 for 12 for 13 measuring 13 measuring 15 performance 13 measuring 16 in 14 functional 15 performance 16 in 18 population 17 this 18 population the present study evaluated the validity , sensitivity and reliability of the edmonton functional assessment tool ( efat2 ) within a uk palliative care setting . 0 ###LEFT-WALL### 3 study 0 ###LEFT-WALL### 4 evaluated 0 ###LEFT-WALL### 26 . 1 the 3 study 2 present 3 study 3 study 4 evaluated 4 evaluated 9 and 4 evaluated 20 within 5 the 6 validity 6 validity 7 , 7 , 8 sensitivity 7 , 9 and 9 and 10 reliability 9 and 11 of 11 of 16 tool 12 the 16 tool 13 edmonton 14 functional 14 functional 15 assessment 15 assessment 16 tool 16 tool 18 efat2 17 ( 18 efat2 18 efat2 19 ) 20 within 25 setting 21 a 25 setting 22 uk 24 care 23 palliative 24 care 24 care 25 setting methods : eleven participants aged 65 years and over [(] mean age 76.5 ± 6.7 years ) receiving rehabilitation in a palliative care inpatient setting were studied . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 4 participants 2 : 5 aged 2 : 8 and 2 : 28 . 3 eleven 4 participants 4 participants 5 aged 5 aged 7 years 6 65 7 years 8 and 18 receiving 8 and 27 studied 9 over 16 years 9 over 17 ) 9 over 18 receiving 11 mean 16 years 12 age 16 years 13 76.5 16 years 14 ± 16 years 15 6.7 16 years 18 receiving 19 rehabilitation 18 receiving 26 were 19 rehabilitation 20 in 19 rehabilitation 25 setting 20 in 24 inpatient 21 a 24 inpatient 22 palliative 24 inpatient 23 care 24 inpatient 26 were 27 studied concurrent validity was assessed by comparing efat2 with the barthel index . 0 ###LEFT-WALL### 2 validity 0 ###LEFT-WALL### 4 assessed 0 ###LEFT-WALL### 12 . 1 concurrent 2 validity 2 validity 3 was 3 was 4 assessed 4 assessed 5 by 5 by 6 comparing 6 comparing 7 efat2 6 comparing 8 with 8 with 11 index 9 the 11 index 10 barthel 11 index [inter] - rater reliability of efat2 was examined using a sample of four participants recruited from a cancer care ward . 0 ###LEFT-WALL### 2 - 0 ###LEFT-WALL### 8 examined 0 ###LEFT-WALL### 21 . 2 - 4 reliability 3 rater 4 reliability 4 reliability 5 of 4 reliability 7 was 5 of 6 efat2 7 was 8 examined 8 examined 9 using 9 using 11 sample 10 a 11 sample 11 sample 12 of 11 sample 15 recruited 12 of 14 participants 13 four 14 participants 15 recruited 16 from 16 from 20 ward 17 a 18 cancer 17 a 20 ward 18 cancer 20 ward 19 care 20 ward results : a significant negative correlation was observed between the barthel index and efat2 ( r = - 0.765 , p = 0.01 ) and both measures were found to be sensitive as determined by cohen 's effect size ( [efat2] = 0.60 , barthel index = 0.72 [ )( 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 34 determined 0 ###LEFT-WALL### 50 )( 2 : 6 correlation 2 : 8 observed 2 : 25 and 2 : 31 be 3 a 4 significant 3 a 6 correlation 4 significant 6 correlation 5 negative 6 correlation 6 correlation 7 was 7 was 8 observed 8 observed 9 between 8 observed 22 = 9 between 14 efat2 10 the 14 efat2 11 barthel 12 index 12 index 13 and 13 and 14 efat2 14 efat2 17 = 15 ( 17 = 16 r 17 = 17 = 18 - 18 - 19 0.765 18 - 22 = 20 , 22 = 21 p 22 = 22 = 23 0.01 22 = 24 ) 25 and 27 measures 25 and 29 found 26 both 27 measures 27 measures 28 were 28 were 29 found 29 found 30 to 30 to 31 be 31 be 32 sensitive 31 be 33 as 33 as 34 determined 34 determined 35 by 34 determined 44 , 34 determined 46 index 34 determined 47 = 35 by 39 size 36 cohen 37 's 37 's 39 size 38 effect 39 size 39 size 43 0.60 40 ( 43 0.60 42 = 43 0.60 43 0.60 44 , 45 barthel 46 index 46 index 47 = 47 = 48 0.72 high [inter] - rater reliability was noted for efat2 ( icc3 , 1 = 0.85 ) and the agreement between scores was confirmed by bland - altman analysis . 0 ###LEFT-WALL### 5 reliability 0 ###LEFT-WALL### 7 noted 0 ###LEFT-WALL### 17 and 1 high 3 - 1 high 5 reliability 4 rater 5 reliability 5 reliability 6 was 6 was 7 noted 7 noted 8 for 7 noted 14 = 8 for 9 efat2 9 efat2 11 icc3 10 ( 11 icc3 11 icc3 12 , 12 , 14 = 13 1 14 = 14 = 15 0.85 14 = 16 ) 17 and 19 agreement 17 and 23 confirmed 18 the 19 agreement 19 agreement 20 between 19 agreement 22 was 20 between 21 scores 22 was 23 confirmed 23 confirmed 24 by 24 by 25 bland 25 bland 28 analysis 26 - 28 analysis 27 altman 28 analysis 28 analysis 29 . conclusions : efat2 showed concurrent validity with the barthel index when used to assess the effects of rehabilitation on participants with advanced cancer . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 3 efat2 2 : 4 showed 2 : 24 . 3 efat2 4 showed 4 showed 6 validity 4 showed 7 with 4 showed 11 when 4 showed 19 on 5 concurrent 6 validity 7 with 10 index 8 the 10 index 9 barthel 10 index 11 when 12 used 12 used 13 to 12 used 14 assess 13 to 14 assess 14 assess 16 effects 15 the 16 effects 16 effects 17 of 17 of 18 rehabilitation 19 on 20 participants 20 participants 21 with 21 with 23 cancer 22 advanced 23 cancer the tool was sensitive to change and was found to be reliable when used by different raters . 0 ###LEFT-WALL### 2 tool 0 ###LEFT-WALL### 7 and 0 ###LEFT-WALL### 18 . 1 the 2 tool 2 tool 7 and 3 was 4 sensitive 3 was 7 and 4 sensitive 5 to 4 sensitive 6 change 5 to 6 change 7 and 8 was 8 was 9 found 9 found 10 to 10 to 11 be 11 be 12 reliable 12 reliable 13 when 13 when 14 used 14 used 15 by 15 by 17 raters 16 different 17 raters the findings indicate that efat2 might be an appropriate outcome measure to use within the palliative care setting . 0 ###LEFT-WALL### 2 findings 0 ###LEFT-WALL### 3 indicate 0 ###LEFT-WALL### 19 . 1 the 2 findings 2 findings 3 indicate 3 indicate 4 that 4 that 5 efat2 4 that 7 be 5 efat2 6 might 6 might 7 be 7 be 11 measure 8 an 9 appropriate 8 an 11 measure 9 appropriate 10 outcome 10 outcome 11 measure 11 measure 12 to 12 to 13 use 13 use 14 within 14 within 17 care 15 the 17 care 16 palliative 17 care 17 care 18 setting however , the feasibility of using efat2 needs to be explored and larger studies are required to confirm its reliability . 0 ###LEFT-WALL### 4 feasibility 0 ###LEFT-WALL### 8 needs 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 21 . 1 however 2 , 1 however 4 feasibility 3 the 4 feasibility 4 feasibility 5 of 4 feasibility 8 needs 5 of 6 using 6 using 7 efat2 8 needs 9 to 8 needs 11 explored 9 to 10 be 10 be 11 explored 12 and 14 studies 12 and 16 required 13 larger 14 studies 14 studies 15 are 15 are 16 required 16 required 17 to 16 required 18 confirm 17 to 18 confirm 18 confirm 20 reliability 19 its 20 reliability summary : previous studies on the association between uric acid and bone mineral density yielded conflicting results . 0 ###LEFT-WALL### 1 summary 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 18 . 1 summary 2 : 2 : 4 studies 3 previous 4 studies 4 studies 5 on 5 on 7 association 6 the 7 association 7 association 8 between 8 between 10 acid 9 uric 10 acid 11 and 14 density 11 and 17 results 12 bone 13 mineral 13 mineral 14 density 14 density 15 yielded 14 density 16 conflicting 14 density 17 results in this study , we demonstrated positive [association] between uric acid and lumbar spine bone mineral density in peri - and postmenopausal japanese women . 0 ###LEFT-WALL### 5 we 0 ###LEFT-WALL### 6 demonstrated 0 ###LEFT-WALL### 25 . 1 in 3 study 1 in 4 , 1 in 5 we 2 this 3 study 5 we 6 demonstrated 6 demonstrated 17 density 6 demonstrated 18 in 7 positive 9 between 7 positive 12 and 9 between 11 acid 10 uric 11 acid 12 and 13 lumbar 12 and 14 spine 14 spine 17 density 15 bone 17 density 16 mineral 17 density 18 in 21 and 19 peri 21 and 20 - 21 and 21 and 24 women 22 postmenopausal 24 women 23 japanese 24 women further research is needed to elucidate the underlying mechanism . 0 ###LEFT-WALL### 2 research 0 ###LEFT-WALL### 4 needed 0 ###LEFT-WALL### 10 . 1 further 2 research 2 research 3 is 3 is 4 needed 4 needed 5 to 5 to 6 elucidate 6 elucidate 9 mechanism 7 the 9 mechanism 8 underlying 9 mechanism introduction : oxidative stress has been implicated in the pathogenesis of osteoporosis . 0 ###LEFT-WALL### 1 introduction 0 ###LEFT-WALL### 2 : 2 : 4 stress 2 : 7 implicated 2 : 13 . 3 oxidative 4 stress 4 stress 5 has 5 has 6 been 6 been 7 implicated 7 implicated 8 in 8 in 10 pathogenesis 9 the 10 pathogenesis 10 pathogenesis 11 of 11 of 12 osteoporosis uric acid , a potent antioxidant substance , has been associated with bone mineral density but previous studies have yielded conflicting results . 0 ###LEFT-WALL### 2 acid 0 ###LEFT-WALL### 11 associated 0 ###LEFT-WALL### 16 but 0 ###LEFT-WALL### 23 . 1 uric 2 acid 2 acid 7 substance 2 acid 9 has 3 , 7 substance 4 a 5 potent 4 a 7 substance 5 potent 6 antioxidant 6 antioxidant 7 substance 7 substance 8 , 9 has 10 been 10 been 11 associated 11 associated 12 with 12 with 15 density 13 bone 15 density 14 mineral 15 density 16 but 18 studies 16 but 20 yielded 17 previous 18 studies 18 studies 19 have 19 have 20 yielded 20 yielded 22 results 21 conflicting 22 results the objective of the study was to examine the association between serum uric acid and lumbar spine bone mineral density ( bmd ) . 0 ###LEFT-WALL### 2 objective 0 ###LEFT-WALL### 24 . 1 the 2 objective 2 objective 3 of 2 objective 6 was 3 of 5 study 4 the 5 study 6 was 7 to 6 was 8 examine 7 to 8 examine 8 examine 10 association 8 examine 11 between 9 the 10 association 11 between 15 and 12 serum 14 acid 13 uric 14 acid 14 acid 15 and 15 and 20 density 15 and 22 bmd 16 lumbar 17 spine 17 spine 20 density 18 bone 20 density 19 mineral 20 density 21 ( 22 bmd 22 bmd 23 ) methods : this was a retrospective analysis of medical records of 615 women , aged 45 - 75 years , who had lumbar spine bmd measurement by dual - energy x - ray absorptiometry as a part of health [checkup] from august 2011 to july 2012 . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 47 . 2 : 3 this 2 : 4 was 2 : 32 - 3 this 4 was 4 was 7 analysis 5 a 6 retrospective 5 a 7 analysis 6 retrospective 7 analysis 7 analysis 8 of 7 analysis 21 who 7 analysis 22 had 8 of 10 records 9 medical 10 records 10 records 11 of 11 of 13 women 12 615 13 women 13 women 15 aged 13 women 19 years 14 , 15 aged 15 aged 16 45 15 aged 17 - 17 - 19 years 18 75 19 years 19 years 20 , 21 who 22 had 22 had 26 measurement 22 had 27 by 23 lumbar 26 measurement 24 spine 26 measurement 25 bmd 26 measurement 27 by 30 energy 28 dual 29 - 28 dual 30 energy 30 energy 31 x 32 - 34 absorptiometry 33 ray 34 absorptiometry 34 absorptiometry 35 as 34 absorptiometry 38 of 35 as 37 part 36 a 37 part 38 of 39 health 39 health 41 from 39 health 44 to 41 from 42 august 42 august 43 2011 44 to 45 july 45 july 46 2012 results : mean serum uric acid level was 4.7 mg/dl . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 3 mean 0 ###LEFT-WALL### 11 . 1 results 2 : 2 : 3 mean 3 mean 7 level 3 mean 8 was 4 serum 7 level 5 uric 6 acid 6 acid 7 level 7 level 8 was 8 was 10 mg/dl 9 4.7 10 mg/dl uric acid rapidly increased until the age of 60 years , and then decelerated but continued to increase thereafter . 0 ###LEFT-WALL### 2 acid 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 20 . 1 uric 2 acid 2 acid 12 and 3 rapidly 4 increased 4 increased 5 until 4 increased 12 and 5 until 7 age 6 the 7 age 7 age 8 of 8 of 10 years 9 60 10 years 11 , 12 and 12 and 15 but 13 then 14 decelerated 14 decelerated 15 but 15 but 16 continued 16 continued 17 to 16 continued 18 increase 17 to 18 increase 18 increase 19 thereafter the association between lumbar spine bmd and uric acid remained significantly positive after excluding women older than 60 years . 0 ###LEFT-WALL### 7 and 0 ###LEFT-WALL### 10 remained 0 ###LEFT-WALL### 20 . 1 the 2 association 2 association 3 between 2 association 7 and 3 between 6 bmd 4 lumbar 5 spine 5 spine 6 bmd 7 and 9 acid 7 and 10 remained 8 uric 9 acid 10 remained 11 significantly 10 remained 12 positive 12 positive 13 after 13 after 14 excluding 14 excluding 15 women 15 women 16 older 16 older 17 than 17 than 19 years 18 60 19 years conclusion : the present study showed that higher uric acid levels were linearly associated with higher lumbar spine bmd in peri - and postmenopausal japanese women . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 6 showed 0 ###LEFT-WALL### 27 . 1 conclusion 2 : 2 : 4 present 3 the 4 present 4 present 5 study 4 present 6 showed 5 study 6 showed 6 showed 7 that 7 that 11 levels 7 that 14 associated 8 higher 11 levels 9 uric 11 levels 10 acid 11 levels 11 levels 12 were 12 were 13 linearly 12 were 14 associated 14 associated 15 with 15 with 23 and 16 higher 18 spine 17 lumbar 18 spine 18 spine 19 bmd 19 bmd 20 in 19 bmd 23 and 20 in 21 peri 22 - 23 and 23 and 26 women 24 postmenopausal 26 women 25 japanese 26 women further research is needed to elucidate the underlying mechanism of the association between uric acid and bmd . 0 ###LEFT-WALL### 2 research 0 ###LEFT-WALL### 4 needed 0 ###LEFT-WALL### 18 . 1 further 2 research 2 research 3 is 3 is 4 needed 4 needed 5 to 5 to 6 elucidate 6 elucidate 9 mechanism 6 elucidate 13 between 7 the 9 mechanism 8 underlying 9 mechanism 9 mechanism 10 of 10 of 12 association 11 the 12 association 13 between 16 and 14 uric 15 acid 15 acid 16 and 16 and 17 bmd epigenetics is an emerging field in ophthalmology and has opened a new avenue for understanding ocular development and ocular diseases related to aging and environment . 0 ###LEFT-WALL### 1 epigenetics 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 26 . 1 epigenetics 8 and 2 is 5 field 2 is 8 and 3 an 5 field 4 emerging 5 field 5 field 6 in 6 in 7 ophthalmology 8 and 9 has 8 and 24 and 9 has 10 opened 11 a 13 avenue 12 new 13 avenue 13 avenue 14 for 13 avenue 18 and 14 for 17 development 15 understanding 17 development 16 ocular 17 development 18 and 20 diseases 18 and 21 related 18 and 24 and 19 ocular 20 diseases 21 related 22 to 22 to 23 aging 24 and 25 environment epigenetic mechanisms , including dna methylation , histone modifications , chromatin remodeling , and deployment [of] [non] - coding rnas , result in the heritable silencing of gene expression without any change in dna sequence . 0 ###LEFT-WALL### 14 and 0 ###LEFT-WALL### 22 result 0 ###LEFT-WALL### 36 . 1 epigenetic 2 mechanisms 2 mechanisms 3 , 3 , 6 methylation 3 , 7 , 4 including 6 methylation 5 dna 6 methylation 7 , 9 modifications 7 , 10 , 8 histone 9 modifications 10 , 12 remodeling 10 , 14 and 11 chromatin 12 remodeling 13 , 14 and 14 and 15 deployment 14 and 19 coding 14 and 22 result 18 - 19 coding 19 coding 20 rnas 19 coding 21 , 22 result 23 in 22 result 30 without 23 in 26 silencing 24 the 26 silencing 25 heritable 26 silencing 26 silencing 27 of 27 of 29 expression 28 gene 29 expression 30 without 32 change 31 any 32 change 32 change 33 in 33 in 35 sequence 34 dna 35 sequence accumulating evidence suggests a potential link between gene expression , chromatin structure , [non] - coding rnas , and cellular differentiation during ocular development . 0 ###LEFT-WALL### 1 accumulating 0 ###LEFT-WALL### 3 suggests 0 ###LEFT-WALL### 25 . 1 accumulating 2 evidence 1 accumulating 3 suggests 3 suggests 19 and 3 suggests 22 during 4 a 5 potential 4 a 6 link 5 potential 6 link 6 link 7 between 6 link 19 and 7 between 9 expression 8 gene 9 expression 9 expression 12 structure 9 expression 16 coding 10 , 12 structure 11 chromatin 12 structure 12 structure 13 , 15 - 16 coding 16 coding 17 rnas 16 coding 18 , 19 and 21 differentiation 20 cellular 21 differentiation 22 during 24 development 23 ocular 24 development disruption of the balance of epigenetic networks could become the etiology of several ocular diseases . 0 ###LEFT-WALL### 1 disruption 0 ###LEFT-WALL### 9 become 0 ###LEFT-WALL### 16 . 1 disruption 2 of 1 disruption 8 could 2 of 4 balance 3 the 4 balance 4 balance 5 of 5 of 7 networks 6 epigenetic 7 networks 8 could 9 become 9 become 11 etiology 10 the 11 etiology 11 etiology 12 of 12 of 15 diseases 13 several 15 diseases 14 ocular 15 diseases here , we summarized the current knowledge about epigenetic regulatory mechanisms in ocular development and diseases . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 summarized 0 ###LEFT-WALL### 17 . 1 here 2 , 1 here 3 we 3 we 4 summarized 4 summarized 7 knowledge 4 summarized 8 about 4 summarized 12 in 5 the 7 knowledge 6 current 7 knowledge 8 about 11 mechanisms 9 epigenetic 11 mechanisms 10 regulatory 11 mechanisms 12 in 15 and 13 ocular 14 development 14 development 15 and 15 and 16 diseases purpose : to assess the relationship of posttraumatic stress disorder ( ptsd ) with health functioning and disability in vietnam - era veterans . 0 ###LEFT-WALL### 1 purpose 0 ###LEFT-WALL### 2 : 2 : 3 to 2 : 4 assess 2 : 21 - 2 : 24 . 3 to 4 assess 4 assess 6 relationship 4 assess 19 in 5 the 6 relationship 6 relationship 7 of 6 relationship 14 with 7 of 10 disorder 8 posttraumatic 9 stress 9 stress 10 disorder 10 disorder 12 ptsd 11 ( 12 ptsd 12 ptsd 13 ) 14 with 17 and 15 health 16 functioning 15 health 17 and 17 and 18 disability 19 in 20 vietnam 21 - 23 veterans 22 era 23 veterans methods : a cross - sectional study of functioning and disability in male vietnam - era veteran twins . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 15 - 1 methods 2 : 2 : 4 cross 3 a 4 cross 4 cross 10 and 5 - 10 and 6 sectional 7 study 7 study 8 of 7 study 10 and 8 of 9 functioning 10 and 11 disability 10 and 12 in 10 and 15 - 12 in 14 vietnam 13 male 14 vietnam 15 - 18 twins 15 - 19 . 16 era 18 twins 17 veteran 18 twins ptsd was measured by the composite international diagnostic interview ; health functioning and disability were assessed using the veterans rand 36 - item health survey ( vr - 36 ) and the world health organization disability assessment schedule 2.0 ( whodas 2.0 ) . 0 ###LEFT-WALL### 1 ptsd 0 ###LEFT-WALL### 2 was 0 ###LEFT-WALL### 10 ; 0 ###LEFT-WALL### 44 . 1 ptsd 2 was 2 was 3 measured 3 measured 4 by 4 by 9 interview 5 the 9 interview 6 composite 7 international 7 international 8 diagnostic 8 diagnostic 9 interview 10 ; 13 and 10 ; 16 assessed 10 ; 22 - 11 health 12 functioning 11 health 13 and 13 and 14 disability 13 and 15 were 15 were 16 assessed 16 assessed 17 using 17 using 20 rand 18 the 20 rand 19 veterans 20 rand 20 rand 21 36 22 - 25 survey 23 item 24 health 24 health 25 survey 25 survey 31 and 26 ( 31 and 27 vr 29 36 27 vr 31 and 28 - 29 36 29 36 30 ) 31 and 38 schedule 31 and 41 whodas 31 and 43 ) 32 the 38 schedule 33 world 34 health 34 health 35 organization 35 organization 36 disability 36 disability 37 assessment 37 assessment 38 schedule 38 schedule 39 2.0 40 ( 41 whodas 41 whodas 42 2.0 41 whodas 43 ) all data [collection] took place between 2010 and 2012 . 0 ###LEFT-WALL### 2 data 0 ###LEFT-WALL### 4 took 0 ###LEFT-WALL### 10 . 1 all 2 data 2 data 4 took 4 took 5 place 4 took 6 between 6 between 8 and 7 2010 8 and 8 and 9 2012 results : average age of the 5,574 participating veterans ( 2,102 vietnam theater [and] 3,472 [non] - theater ) was 61.0 years . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 23 . 2 : 4 age 2 : 20 was 3 average 4 age 4 age 5 of 4 age 20 was 5 of 9 veterans 6 the 7 5,574 7 5,574 9 veterans 8 participating 9 veterans 9 veterans 13 theater 9 veterans 18 theater 10 ( 13 theater 11 2,102 13 theater 12 vietnam 13 theater 13 theater 15 3,472 13 theater 17 - 17 - 18 theater 18 theater 19 ) 20 was 22 years 21 61.0 22 years veterans with ptsd had poorer health functioning across all domains of vr - 36 and increased disability for all subscales of whodas 2.0 ( [all] p < .001[!] ) compared with veterans without ptsd . 0 ###LEFT-WALL### 1 veterans 0 ###LEFT-WALL### 13 - 0 ###LEFT-WALL### 35 . 1 veterans 2 with 1 veterans 4 had 2 with 3 ptsd 4 had 6 health 4 had 8 across 5 poorer 6 health 6 health 7 functioning 8 across 10 domains 9 all 10 domains 10 domains 11 of 11 of 12 vr 13 - 14 36 13 - 15 and 15 and 17 disability 15 and 30 compared 16 increased 17 disability 17 disability 18 for 17 disability 21 of 17 disability 27 < 17 disability 30 compared 18 for 20 subscales 19 all 20 subscales 21 of 22 whodas 23 2.0 27 < 24 ( 27 < 26 p 27 < 27 < 28 .001[!] 27 < 29 ) 30 compared 31 with 31 with 32 veterans 31 with 33 without 33 without 34 ptsd combat exposure , [independent] of ptsd status , was associated with lower pcs and mcs scores and increased disability ( [all] p < .05[!] , [for] trend ) . 0 ###LEFT-WALL### 2 exposure 0 ###LEFT-WALL### 10 associated 0 ###LEFT-WALL### 29 . 1 combat 2 exposure 2 exposure 5 of 2 exposure 9 was 3 , 5 of 5 of 7 status 5 of 8 , 6 ptsd 7 status 9 was 10 associated 10 associated 11 with 11 with 14 and 12 lower 13 pcs 13 pcs 14 and 14 and 27 trend 14 and 28 ) 15 mcs 27 trend 16 scores 17 and 17 and 19 disability 17 and 23 < 17 and 27 trend 18 increased 19 disability 20 ( 23 < 22 p 23 < 23 < 24 .05[!] 23 < 25 , [within] - pair analyses in twins discordant for ptsd produced consistent findings . 0 ###LEFT-WALL### 2 - 0 ###LEFT-WALL### 10 produced 0 ###LEFT-WALL### 13 . 2 - 4 analyses 3 pair 4 analyses 4 analyses 5 in 4 analyses 10 produced 5 in 6 twins 6 twins 7 discordant 7 discordant 8 for 8 for 9 ptsd 10 produced 12 findings 11 consistent 12 findings conclusions : vietnam - era veterans with ptsd have diminished functioning and increased disability . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 4 - 0 ###LEFT-WALL### 15 . 1 conclusions 2 : 2 : 3 vietnam 4 - 6 veterans 5 era 6 veterans 6 veterans 7 with 6 veterans 12 and 7 with 8 ptsd 9 have 10 diminished 9 have 12 and 10 diminished 11 functioning 12 and 13 increased 12 and 14 disability the poor functional status of aging combat [-] exposed veterans is of particular concern . 0 ###LEFT-WALL### 4 status 0 ###LEFT-WALL### 11 is 0 ###LEFT-WALL### 15 . 1 the 4 status 2 poor 4 status 3 functional 4 status 4 status 5 of 4 status 7 combat 4 status 9 exposed 4 status 11 is 5 of 6 aging 7 combat 9 exposed 9 exposed 10 veterans 11 is 12 of 12 of 14 concern 13 particular 14 concern purposes : colonoscopic evidence of epidemiological trends in diverticulosis and diverticular bleeding is scarce . 0 ###LEFT-WALL### 1 purposes 0 ###LEFT-WALL### 2 : 2 : 4 evidence 2 : 13 is 2 : 15 . 3 colonoscopic 4 evidence 4 evidence 5 of 4 evidence 8 in 4 evidence 13 is 5 of 7 trends 6 epidemiological 7 trends 8 in 10 and 9 diverticulosis 10 and 10 and 12 bleeding 11 diverticular 12 bleeding 13 is 14 scarce we evaluated trends in diverticular disease and associated factors over 9 years . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 7 and 0 ###LEFT-WALL### 13 . 1 we 7 and 2 evaluated 3 trends 2 evaluated 4 in 2 evaluated 7 and 4 in 6 disease 5 diverticular 6 disease 7 and 8 associated 8 associated 9 factors 8 associated 10 over 10 over 12 years 11 9 12 years methods : twenty - eight thousand one hundred ninety - two patients who underwent colonoscopy at an emergency hospital were reviewed from an electronic endoscopy database . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 27 . 1 methods 2 : 2 : 6 thousand 3 twenty 4 - 4 - 5 eight 4 - 6 thousand 6 thousand 8 hundred 6 thousand 21 reviewed 7 one 8 hundred 8 hundred 12 patients 8 hundred 20 were 8 hundred 21 reviewed 9 ninety 10 - 10 - 11 two 10 - 12 patients 12 patients 13 who 12 patients 14 underwent 12 patients 20 were 13 who 14 underwent 14 underwent 15 colonoscopy 14 underwent 16 at 16 at 19 hospital 17 an 19 hospital 18 emergency 19 hospital 21 reviewed 22 from 22 from 26 database 23 an 26 database 24 electronic 26 database 25 endoscopy 26 database diverticula were classified as right - sided , [left] - sided , and [bilateral] types , and time trends in the proportion in diverticulosis , type , and diverticular bleeding [were] determined . 0 ###LEFT-WALL### 1 diverticula 0 ###LEFT-WALL### 2 were 0 ###LEFT-WALL### 6 - 1 diverticula 2 were 2 were 3 classified 3 classified 4 as 4 as 5 right 6 - 8 , 7 sided 8 , 8 , 13 and 10 - 13 and 11 sided 13 and 12 , 13 and 13 and 17 and 15 types 17 and 16 , 17 and 17 and 18 time 18 time 19 trends 18 time 20 in 18 time 23 in 20 in 22 proportion 21 the 22 proportion 23 in 28 and 24 diverticulosis 25 , 25 , 26 type 25 , 28 and 27 , 28 and 28 and 30 bleeding 28 and 33 . 29 diverticular 30 bleeding 30 bleeding 32 determined associations of age ( ≤39 , 40 - 59 , and ≥60 years ) , sex , and year increase with disease and odds ratios were estimated using logistic regression . 0 ###LEFT-WALL### 18 and 0 ###LEFT-WALL### 31 . 1 associations 2 of 1 associations 18 and 2 of 3 age 3 age 13 years 3 age 16 sex 4 ( 13 years 5 ≤39 8 - 5 ≤39 11 and 6 , 8 - 7 40 8 - 8 - 9 59 8 - 10 , 11 and 12 ≥60 11 and 13 years 13 years 14 ) 15 , 16 sex 16 sex 17 , 18 and 20 increase 18 and 21 with 18 and 27 estimated 19 year 20 increase 21 with 23 and 22 disease 23 and 23 and 24 odds 23 and 25 ratios 23 and 26 were 25 ratios 26 were 27 estimated 28 using 28 using 30 regression 29 logistic 30 regression results : diverticulosis was identified in 6,150 patients ( 20.3 % ; mean age , 67.6 years [ )(and [was] predominantly right - [sided] ( 48.0 % ) . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 29 . 2 : 3 diverticulosis 2 : 5 identified 2 : 12 ; 3 diverticulosis 4 was 4 was 5 identified 5 identified 6 in 6 in 8 patients 7 6,150 8 patients 8 patients 11 % 9 ( 11 % 10 20.3 11 % 11 % 12 ; 12 ; 13 mean 13 mean 14 age 14 age 19 )(and 14 age 27 % 15 , 19 )(and 16 67.6 17 years 17 years 19 )(and 19 )(and 22 right 19 )(and 23 - 21 predominantly 22 right 25 ( 27 % 26 48.0 27 % 27 % 28 ) diverticular bleeding was found in 427 ( 1.5 % [;] mean age , 69.7 years ) and was predominantly bilateral [(] 47.0 % [ )( 0 ###LEFT-WALL### 2 bleeding 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 25 )( 1 diverticular 2 bleeding 2 bleeding 17 and 3 was 4 found 3 was 17 and 4 found 5 in 5 in 6 427 6 427 12 age 6 427 15 years 7 ( 12 age 8 1.5 9 % 9 % 12 age 11 mean 12 age 12 age 13 , 13 , 15 years 14 69.7 15 years 15 years 16 ) 17 and 18 was 17 and 23 % 18 was 20 bilateral 19 predominantly 20 bilateral 22 47.0 23 % proportion of colonic diverticulosis increased significantly ( p < 0.01 [for] [trend] ) from 66.0 % ( 1,424/2,157 ) in 2003 to 70.1 % ( 2,914/4,159 ) in 2011 and was associated ( p < 0.01 ) with an increased number of patients aged ≥60 years . 0 ###LEFT-WALL### 1 proportion 0 ###LEFT-WALL### 30 and 0 ###LEFT-WALL### 47 . 1 proportion 2 of 1 proportion 30 and 2 of 4 diverticulosis 3 colonic 4 diverticulosis 5 increased 6 significantly 5 increased 9 < 5 increased 14 from 5 increased 20 in 5 increased 28 in 5 increased 30 and 7 ( 9 < 8 p 9 < 9 < 10 0.01 9 < 13 ) 14 from 16 % 15 66.0 16 % 16 % 18 1,424/2,157 17 ( 18 1,424/2,157 18 1,424/2,157 19 ) 20 in 24 % 21 2003 22 to 22 to 23 70.1 22 to 24 % 24 % 26 2,914/4,159 25 ( 26 2,914/4,159 26 2,914/4,159 27 ) 28 in 29 2011 30 and 31 was 30 and 38 with 31 was 32 associated 32 associated 35 < 33 ( 35 < 34 p 35 < 35 < 36 0.01 35 < 37 ) 38 with 41 number 38 with 46 years 39 an 41 number 40 increased 41 number 41 number 42 of 41 number 44 aged 42 of 43 patients 44 aged 45 ≥60 proportion of diverticular bleeding increased significantly ( p < 0.01 [for] [trend] ) from 1.02 % ( 22/2,157 ) in 2003 to 1.67 % ( 69/4,159 ) in 2011 and was associated ( p = 0.04 ) with an increased number of patients aged 40 - 59 years . 0 ###LEFT-WALL### 1 proportion 0 ###LEFT-WALL### 30 and 0 ###LEFT-WALL### 49 . 1 proportion 2 of 1 proportion 30 and 2 of 4 bleeding 3 diverticular 4 bleeding 5 increased 6 significantly 5 increased 9 < 5 increased 14 from 5 increased 20 in 5 increased 28 in 5 increased 30 and 7 ( 9 < 8 p 9 < 9 < 10 0.01 9 < 13 ) 14 from 16 % 15 1.02 16 % 16 % 18 22/2,157 17 ( 18 22/2,157 18 22/2,157 19 ) 20 in 21 2003 21 2003 22 to 22 to 24 % 23 1.67 24 % 24 % 26 69/4,159 25 ( 26 69/4,159 26 69/4,159 27 ) 28 in 29 2011 30 and 31 was 30 and 35 = 30 and 38 with 31 was 32 associated 33 ( 35 = 34 p 35 = 35 = 36 0.04 35 = 37 ) 38 with 43 patients 38 with 48 years 39 an 41 number 40 increased 41 number 41 number 42 of 41 number 43 patients 42 of 43 patients 43 patients 44 aged 44 aged 46 - 45 40 46 - 46 - 47 59 diverticulosis , right and bilateral type , and diverticular bleeding were independently associated with the 9 [-] year trend after adjustment by age and sex . 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 13 associated 0 ###LEFT-WALL### 26 . 1 diverticulosis 2 , 1 diverticulosis 8 and 3 right 4 and 4 and 6 type 4 and 8 and 5 bilateral 6 type 7 , 8 and 8 and 10 bleeding 8 and 11 were 9 diverticular 10 bleeding 11 were 12 independently 11 were 13 associated 13 associated 14 with 13 associated 22 by 14 with 19 trend 15 the 19 trend 16 9 18 year 18 year 19 trend 19 trend 20 after 20 after 21 adjustment 22 by 24 and 23 age 24 and 24 and 25 sex conclusions : colonic diverticulosis and diverticular bleeding are prevalent and increasing in japan . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 14 . 2 : 5 and 2 : 8 are 3 colonic 4 diverticulosis 4 diverticulosis 5 and 5 and 7 bleeding 5 and 8 are 6 diverticular 7 bleeding 8 are 10 and 8 are 12 in 9 prevalent 10 and 10 and 11 increasing 12 in 13 japan given the significant association of age with this trend , both diseases can be expected to increase for decades to come . 0 ###LEFT-WALL### 12 diseases 0 ###LEFT-WALL### 15 expected 0 ###LEFT-WALL### 22 . 1 given 4 association 1 given 7 with 1 given 10 , 1 given 12 diseases 2 the 4 association 3 significant 4 association 4 association 5 of 5 of 6 age 7 with 9 trend 8 this 9 trend 11 both 12 diseases 12 diseases 13 can 13 can 14 be 14 be 15 expected 15 expected 16 to 15 expected 17 increase 16 to 17 increase 17 increase 18 for 17 increase 20 to 18 for 19 decades 20 to 21 come background : resources to help the older aged ( ≥65 year olds ) [manage] [their] medicines should probably target those [in] greatest need . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 24 . 2 : 3 resources 2 : 23 need 3 resources 4 to 3 resources 16 medicines 3 resources 19 target 3 resources 23 need 4 to 5 help 6 the 16 medicines 7 older 16 medicines 8 aged 12 olds 8 aged 16 medicines 9 ( 12 olds 10 ≥65 12 olds 11 year 12 olds 12 olds 13 ) 16 medicines 17 should 17 should 19 target 18 probably 19 target 19 target 22 greatest 20 those 22 greatest the [older] [-] aged have many different types of living circumstances . 0 ###LEFT-WALL### 4 aged 0 ###LEFT-WALL### 5 have 0 ###LEFT-WALL### 12 . 1 the 4 aged 4 aged 5 have 5 have 11 circumstances 6 many 8 types 7 different 8 types 8 types 9 of 8 types 11 circumstances 9 of 11 circumstances 10 living 11 circumstances there are different locations [(] urban , rural ) [,] different types of housing ( in the community or [in] retirement villages ) , different living arrangements ( living alone [or] with others ) , and different socioeconomic status ( ses ) circumstances . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 are 0 ###LEFT-WALL### 7 , 0 ###LEFT-WALL### 44 . 1 there 2 are 2 are 4 locations 2 are 6 urban 3 different 4 locations 7 , 43 circumstances 8 rural 9 ) 8 rural 12 types 11 different 12 types 12 types 13 of 12 types 36 and 13 of 14 housing 14 housing 16 in 15 ( 16 in 16 in 19 or 16 in 35 , 17 the 18 community 18 community 19 or 19 or 22 villages 19 or 23 ) 19 or 27 arrangements 21 retirement 22 villages 24 , 27 arrangements 25 different 27 arrangements 26 living 27 arrangements 27 arrangements 29 living 27 arrangements 35 , 28 ( 29 living 29 living 30 alone 29 living 32 with 29 living 34 ) 32 with 33 others 35 , 36 and 36 and 39 status 36 and 41 ses 36 and 43 circumstances 37 different 39 status 38 socioeconomic 39 status 40 ( 41 ses 41 ses 42 ) however , there has been limited attention [to] [whether] [these] living circumstances affect adherence [to] medicines in the ≥65 year olds . 0 ###LEFT-WALL### 3 there 0 ###LEFT-WALL### 5 been 0 ###LEFT-WALL### 22 . 1 however 2 , 1 however 3 there 3 there 4 has 4 has 5 been 5 been 11 living 6 limited 11 living 7 attention 11 living 11 living 12 circumstances 11 living 13 affect 12 circumstances 13 affect 13 affect 16 medicines 14 adherence 16 medicines 16 medicines 17 in 17 in 21 olds 18 the 21 olds 19 ≥65 21 olds 20 year 21 olds aim of the review : the aim was to determine whether comparative studies , including logistic regression studies , show that living circumstances affect adherence [to] medicines by the ≥65 year olds . 0 ###LEFT-WALL### 4 review 0 ###LEFT-WALL### 5 : 0 ###LEFT-WALL### 10 determine 0 ###LEFT-WALL### 33 . 1 aim 2 of 2 of 3 the 3 the 4 review 5 : 7 aim 5 : 8 was 6 the 7 aim 7 aim 8 was 8 was 9 to 9 to 10 determine 10 determine 23 circumstances 10 determine 24 affect 11 whether 13 studies 11 whether 20 show 11 whether 23 circumstances 12 comparative 13 studies 13 studies 15 including 13 studies 20 show 14 , 15 including 15 including 18 studies 15 including 19 , 16 logistic 18 studies 17 regression 18 studies 20 show 21 that 22 living 23 circumstances 23 circumstances 24 affect 24 affect 27 medicines 25 adherence 27 medicines 27 medicines 28 by 28 by 32 olds 29 the 32 olds 30 ≥65 32 olds 31 year 32 olds methods : a literature search of medline , cinahl and the internet ( google ) was undertaken . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 5 search 2 : 17 undertaken 2 : 18 . 3 a 4 literature 3 a 5 search 4 literature 5 search 5 search 6 of 5 search 16 was 6 of 10 and 7 medline 9 cinahl 8 , 9 cinahl 9 cinahl 10 and 10 and 12 internet 10 and 14 google 11 the 12 internet 13 ( 14 google 14 google 15 ) 16 was 17 undertaken results : four comparative studies have not shown differences in adherence [to] medicines between the ≥65 year olds living in rural and urban locations , but one study shows lower adherence to medicines for osteoporosis in rural areas compared to metropolitan , and another study shows greater adherence to antihypertensive medicines in rural than urban areas . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 57 . 2 : 5 studies 2 : 8 shown 2 : 26 but 3 four 4 comparative 4 comparative 5 studies 5 studies 6 have 6 have 7 not 6 have 8 shown 8 shown 9 differences 8 shown 18 olds 9 differences 10 in 9 differences 14 between 10 in 13 medicines 11 adherence 13 medicines 14 between 16 ≥65 15 the 16 ≥65 17 year 18 olds 18 olds 19 living 19 living 20 in 20 in 24 locations 21 rural 22 and 22 and 23 urban 22 and 24 locations 25 , 26 but 26 but 31 adherence 26 but 39 compared 27 one 31 adherence 28 study 31 adherence 29 shows 31 adherence 30 lower 31 adherence 31 adherence 32 to 31 adherence 39 compared 32 to 33 medicines 33 medicines 34 for 33 medicines 36 in 34 for 35 osteoporosis 36 in 38 areas 37 rural 38 areas 39 compared 40 to 39 compared 49 to 39 compared 52 in 40 to 43 and 41 metropolitan 43 and 42 , 43 and 43 and 48 adherence 44 another 48 adherence 45 study 48 adherence 46 shows 48 adherence 47 greater 48 adherence 49 to 51 medicines 50 antihypertensive 51 medicines 52 in 56 areas 53 rural 56 areas 54 than 55 urban 55 urban 56 areas there are no comparative studies of adherence [to] medicines in the older - aged living in indigenous communities compared to other communities . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 are 0 ###LEFT-WALL### 23 . 1 there 2 are 2 are 5 studies 3 no 5 studies 4 comparative 5 studies 5 studies 6 of 6 of 9 medicines 7 adherence 9 medicines 9 medicines 10 in 10 in 15 living 11 the 15 living 12 older 13 - 12 older 15 living 14 aged 15 living 15 living 16 in 16 in 18 communities 17 indigenous 18 communities 18 communities 19 compared 19 compared 20 to 20 to 22 communities 21 other 22 communities there is conflicting evidence as to whether living alone , being unmarried , or having [a] low income/worth is associated with nonadherence . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 23 . 1 there 2 is 2 is 4 evidence 2 is 6 to 3 conflicting 4 evidence 5 as 6 to 6 to 7 whether 7 whether 18 income/worth 7 whether 20 associated 8 living 18 income/worth 9 alone 11 being 9 alone 14 or 10 , 11 being 11 being 12 unmarried 11 being 13 , 14 or 15 having 14 or 17 low 17 low 18 income/worth 18 income/worth 19 is 19 is 20 associated 20 associated 21 with 21 with 22 nonadherence preliminary studies have suggested that the older - aged living [in] rental , low ses retirement villages or leasehold , middle ses retirement villages have a lower adherence to medicines than those living in [freehold] , high ses retirement villages . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 4 suggested 0 ###LEFT-WALL### 36 , 0 ###LEFT-WALL### 41 . 1 preliminary 2 studies 2 studies 3 have 3 have 4 suggested 4 suggested 5 that 5 that 12 rental 5 that 21 middle 6 the 12 rental 7 older 8 - 7 older 10 living 9 aged 10 living 10 living 12 rental 12 rental 18 or 13 , 18 or 14 low 16 retirement 15 ses 16 retirement 16 retirement 17 villages 17 villages 18 or 18 or 19 leasehold 18 or 20 , 21 middle 22 ses 22 ses 24 villages 22 ses 34 in 23 retirement 24 villages 24 villages 25 have 25 have 28 adherence 25 have 31 than 25 have 34 in 26 a 28 adherence 27 lower 28 adherence 28 adherence 29 to 29 to 30 medicines 31 than 32 those 32 those 33 living 36 , 40 villages 37 high 40 villages 38 ses 39 retirement 39 retirement 40 villages conclusions : the ≥65 year olds living in rural communities may need extra help with adherence [to] medicines for osteoporosis . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 6 olds 2 : 12 need 2 : 21 . 3 the 6 olds 4 ≥65 6 olds 5 year 6 olds 6 olds 7 living 6 olds 11 may 7 living 8 in 8 in 10 communities 9 rural 10 communities 11 may 12 need 12 need 14 help 12 need 15 with 13 extra 14 help 15 with 18 medicines 16 adherence 18 medicines 18 medicines 19 for 19 for 20 osteoporosis the ≥65 year olds living in rental [or] leasehold retirement villages may require extra assistance/resources to adhere to their medicines . 0 ###LEFT-WALL### 4 olds 0 ###LEFT-WALL### 13 require 0 ###LEFT-WALL### 21 . 1 the 4 olds 2 ≥65 4 olds 3 year 4 olds 4 olds 5 living 4 olds 12 may 5 living 6 in 6 in 11 villages 7 rental 9 leasehold 9 leasehold 11 villages 10 retirement 11 villages 12 may 13 require 13 require 15 assistance/resources 13 require 16 to 13 require 17 adhere 14 extra 15 assistance/resources 16 to 17 adhere 17 adhere 18 to 18 to 20 medicines 19 their 20 medicines further research [is] needed to clarify whether living under certain living circumstances ( e.g [.] living alone , being unmarried , low income [ )(has an effect on adherence , [and] to determine whether the ≥65 year olds living in indigenous communities need [assistance] to be adherent to prescribed medicines . 0 ###LEFT-WALL### 1 further 1 further 2 research 2 research 4 needed 2 research 5 to 2 research 6 clarify 5 to 6 clarify 6 clarify 7 whether 7 whether 8 living 7 whether 19 being 8 living 9 under 8 living 14 e.g 8 living 19 being 9 under 12 circumstances 10 certain 12 circumstances 11 living 12 circumstances 13 ( 14 e.g 14 e.g 16 living 14 e.g 18 , 16 living 17 alone 19 being 20 unmarried 19 being 21 , 19 being 23 income 19 being 25 )(has 22 low 23 income 23 income 25 )(has 25 )(has 27 effect 26 an 27 effect 27 effect 28 on 28 on 29 adherence 29 adherence 32 to 30 , 32 to 32 to 33 determine 33 determine 34 whether 34 whether 38 olds 34 whether 43 need 35 the 38 olds 36 ≥65 38 olds 37 year 38 olds 38 olds 39 living 38 olds 43 need 39 living 40 in 40 in 42 communities 41 indigenous 42 communities 43 need 45 to 43 need 51 . 45 to 46 be 46 be 47 adherent 47 adherent 48 to 48 to 50 medicines 49 prescribed 50 medicines as a multifaceted molecule , p21 plays multiple critical roles in cell cycle regulation , differentiation , apoptosis , dna repair , senescence , aging and stem cell reprogramming . 0 ###LEFT-WALL### 6 p21 0 ###LEFT-WALL### 7 plays 0 ###LEFT-WALL### 15 , 0 ###LEFT-WALL### 30 . 1 as 4 molecule 1 as 5 , 1 as 6 p21 2 a 3 multifaceted 2 a 4 molecule 3 multifaceted 4 molecule 6 p21 7 plays 7 plays 10 roles 7 plays 11 in 8 multiple 10 roles 9 critical 10 roles 11 in 14 regulation 12 cell 14 regulation 13 cycle 14 regulation 15 , 26 and 16 differentiation 17 , 17 , 18 apoptosis 17 , 19 , 19 , 21 repair 19 , 22 , 20 dna 21 repair 22 , 23 senescence 22 , 24 , 24 , 25 aging 24 , 26 and 26 and 29 reprogramming 27 stem 29 reprogramming 28 cell 29 reprogramming the important roles of p21 in the interphase of the cell cycle have been intensively investigated . 0 ###LEFT-WALL### 3 roles 0 ###LEFT-WALL### 16 investigated 0 ###LEFT-WALL### 17 . 1 the 3 roles 2 important 3 roles 3 roles 4 of 3 roles 13 have 4 of 5 p21 5 p21 6 in 6 in 8 interphase 7 the 8 interphase 8 interphase 9 of 9 of 12 cycle 10 the 12 cycle 11 cell 12 cycle 13 have 14 been 14 been 16 investigated 15 intensively 16 investigated the function of p21 in mitosis has been proposed but not systematically studied . 0 ###LEFT-WALL### 2 function 0 ###LEFT-WALL### 9 proposed 0 ###LEFT-WALL### 14 . 1 the 2 function 2 function 3 of 2 function 7 has 3 of 4 p21 4 p21 5 in 5 in 6 mitosis 7 has 8 been 8 been 9 proposed 9 proposed 10 but 10 but 11 not 11 not 12 systematically 12 systematically 13 studied we show here that p21 is abundant in mitosis and binds [to] and inhibits the activity of cdk1/cyclin b1 . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 show 0 ###LEFT-WALL### 20 . 1 we 2 show 2 show 3 here 2 show 4 that 4 that 5 p21 4 that 13 and 5 p21 13 and 6 is 7 abundant 6 is 13 and 7 abundant 8 in 8 in 10 and 9 mitosis 10 and 10 and 11 binds 13 and 14 inhibits 13 and 16 activity 15 the 16 activity 16 activity 17 of 17 of 19 b1 18 cdk1/cyclin 19 b1 deficiency of p21 prolongs the duration of mitosis by extending metaphase , anaphase and cytokinesis . 0 ###LEFT-WALL### 1 deficiency 0 ###LEFT-WALL### 4 prolongs 0 ###LEFT-WALL### 16 . 1 deficiency 2 of 1 deficiency 4 prolongs 2 of 3 p21 4 prolongs 6 duration 5 the 6 duration 6 duration 7 of 7 of 14 and 8 mitosis 9 by 8 mitosis 12 , 9 by 10 extending 10 extending 11 metaphase 12 , 13 anaphase 12 , 14 and 14 and 15 cytokinesis the activity of aurora [b] is reduced and the localization of aurora [b] on the central spindle is disturbed in anaphase cells without p21 . 0 ###LEFT-WALL### 2 activity 0 ###LEFT-WALL### 7 reduced 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 25 . 1 the 2 activity 2 activity 3 of 2 activity 6 is 3 of 4 aurora 6 is 7 reduced 8 and 10 localization 8 and 19 disturbed 9 the 10 localization 10 localization 11 of 10 localization 14 on 10 localization 18 is 11 of 12 aurora 14 on 17 spindle 15 the 17 spindle 16 central 17 spindle 18 is 19 disturbed 19 disturbed 20 in 19 disturbed 23 without 20 in 22 cells 21 anaphase 22 cells 23 without 24 p21 moreover , hct116 p21 [-] [/] [-] , hela and saos - 2 cells depleted of p21 encounter problems in chromosome segregation and cytokinesis . 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 18 encounter 0 ###LEFT-WALL### 25 . 1 moreover 2 , 1 moreover 10 and 3 hct116 4 p21 4 p21 8 , 8 , 9 hela 8 , 10 and 10 and 11 saos 10 and 14 cells 10 and 15 depleted 10 and 16 of 10 and 18 encounter 12 - 13 2 13 2 14 cells 14 cells 15 depleted 16 of 17 p21 18 encounter 19 problems 18 encounter 20 in 20 in 23 and 21 chromosome 22 segregation 22 segregation 23 and 23 and 24 cytokinesis gently inhibiting the mitotic cdk1 or [add] [-] back of p21 rescues segregation [defect] in hct116 p21 - [/] [-] cells . 0 ###LEFT-WALL### 2 inhibiting 0 ###LEFT-WALL### 12 rescues 0 ###LEFT-WALL### 22 . 1 gently 2 inhibiting 2 inhibiting 6 or 2 inhibiting 12 rescues 3 the 5 cdk1 4 mitotic 5 cdk1 5 cdk1 6 or 6 or 9 back 6 or 10 of 10 of 11 p21 12 rescues 13 segregation 12 rescues 15 in 15 in 21 cells 16 hct116 21 cells 17 p21 18 - 17 p21 21 cells our data demonstrate that p21 is important for a fine - tuned control of the cdk1 activity in mitosis , and its proper function facilitates a smooth mitotic progression . 0 ###LEFT-WALL### 2 data 0 ###LEFT-WALL### 3 demonstrate 0 ###LEFT-WALL### 21 and 0 ###LEFT-WALL### 30 . 1 our 2 data 2 data 3 demonstrate 3 demonstrate 4 that 4 that 5 p21 4 that 6 is 5 p21 6 is 6 is 7 important 7 important 8 for 7 important 18 in 8 for 13 control 9 a 10 fine 9 a 13 control 10 fine 11 - 10 fine 13 control 12 tuned 13 control 13 control 14 of 14 of 17 activity 15 the 17 activity 16 cdk1 17 activity 18 in 19 mitosis 20 , 21 and 21 and 24 function 21 and 25 facilitates 22 its 24 function 23 proper 24 function 24 function 25 facilitates 25 facilitates 29 progression 26 a 27 smooth 26 a 29 progression 27 smooth 29 progression 28 mitotic 29 progression given that p21 is downregulated in the majority of tumors , [either] by the loss of tumor suppressors like p53 or by hyperactive oncogenes such as [c] [-] myc , this finding also sheds new light on the molecular mechanisms by which p21 functions as a tumor suppressor [.] 0 ###LEFT-WALL### 1 given 0 ###LEFT-WALL### 11 , 1 given 2 that 1 given 4 is 1 given 6 in 3 p21 4 is 4 is 5 downregulated 6 in 8 majority 7 the 8 majority 8 majority 9 of 9 of 10 tumors 11 , 18 suppressors 11 , 19 like 11 , 21 or 13 by 15 loss 13 by 18 suppressors 14 the 15 loss 15 loss 16 of 16 of 17 tumor 18 suppressors 19 like 19 like 20 p53 21 or 32 finding 22 by 24 oncogenes 22 by 30 , 22 by 32 finding 23 hyperactive 24 oncogenes 24 oncogenes 26 as 25 such 26 as 26 as 29 myc 31 this 32 finding 32 finding 34 sheds 33 also 34 sheds 34 sheds 36 light 35 new 36 light 36 light 37 on 36 light 41 by 37 on 40 mechanisms 38 the 40 mechanisms 39 molecular 40 mechanisms 41 by 42 which 41 by 43 p21 41 by 44 functions 43 p21 44 functions 44 functions 45 as 45 as 48 suppressor 46 a 48 suppressor 47 tumor 48 suppressor as populations continue to grow older , efforts to support the process of aging well are important goals . 0 ###LEFT-WALL### 8 efforts 0 ###LEFT-WALL### 16 are 0 ###LEFT-WALL### 19 . 1 as 2 populations 1 as 3 continue 1 as 7 , 1 as 8 efforts 2 populations 3 continue 3 continue 4 to 3 continue 5 grow 4 to 5 grow 5 grow 6 older 8 efforts 9 to 8 efforts 10 support 8 efforts 16 are 9 to 10 support 10 support 12 process 10 support 15 well 11 the 12 process 12 process 13 of 13 of 14 aging 16 are 18 goals 17 important 18 goals various synonyms are used to cover aging well , such as active aging . 0 ###LEFT-WALL### 2 synonyms 0 ###LEFT-WALL### 4 used 1 various 2 synonyms 2 synonyms 3 are 3 are 4 used 4 used 5 to 4 used 6 cover 5 to 6 cover 6 cover 8 well 7 aging 8 well 8 well 11 as 9 , 11 as 10 such 11 as 11 as 13 aging 11 as 14 . 12 active 13 aging the world health organization published in 2002 the report active ageing : a policy framework that according to the call for papers [,] has brought active ageing to the forefront of international public health awareness . 0 ###LEFT-WALL### 4 organization 0 ###LEFT-WALL### 5 published 0 ###LEFT-WALL### 12 : 1 the 4 organization 2 world 3 health 3 health 4 organization 4 organization 5 published 5 published 6 in 5 published 11 ageing 6 in 7 2002 8 the 9 report 9 report 11 ageing 10 active 11 ageing 12 : 15 framework 12 : 25 brought 12 : 36 . 13 a 15 framework 14 policy 15 framework 15 framework 16 that 15 framework 24 has 15 framework 25 brought 16 that 18 to 16 that 24 has 17 according 18 to 18 to 20 call 19 the 20 call 20 call 21 for 21 for 22 papers 25 brought 27 ageing 25 brought 28 to 26 active 27 ageing 28 to 30 forefront 29 the 30 forefront 30 forefront 31 of 31 of 35 awareness 32 international 33 public 33 public 35 awareness 34 health 35 awareness the 2010 toronto charter for physical activity : a global call for action was singled out in the call for papers as a key document promoting physical activity one goal of the 2002 who active aging policy framework . 0 ###LEFT-WALL### 7 activity 0 ###LEFT-WALL### 8 : 0 ###LEFT-WALL### 39 . 1 the 2 2010 2 2010 7 activity 3 toronto 4 charter 4 charter 5 for 4 charter 7 activity 5 for 6 physical 8 : 10 global 8 : 15 singled 9 a 10 global 10 global 11 call 10 global 14 was 10 global 15 singled 11 call 12 for 11 call 14 was 12 for 13 action 15 singled 16 out 15 singled 17 in 15 singled 30 goal 17 in 19 call 18 the 19 call 19 call 20 for 19 call 26 promoting 20 for 21 papers 21 papers 22 as 22 as 25 document 23 a 25 document 24 key 25 document 26 promoting 28 activity 27 physical 28 activity 29 one 30 goal 30 goal 31 of 31 of 38 framework 32 the 38 framework 33 2002 34 who 34 who 38 framework 35 active 37 policy 36 aging 37 policy 37 policy 38 framework media are to report to the public topics of importance to them . 0 ###LEFT-WALL### 4 report 1 media 2 are 2 are 3 to 2 are 4 report 3 to 4 report 4 report 5 to 4 report 11 to 4 report 13 . 5 to 8 topics 6 the 8 topics 7 public 8 topics 8 topics 9 of 9 of 10 importance 11 to 12 them we investigated the newspaper coverage of aging well and synonymous terms such as active aging through the lens of the 2002 who active aging policy framework and the 2010 toronto charter for physical activity . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 investigated 0 ###LEFT-WALL### 35 . 1 we 2 investigated 2 investigated 9 and 2 investigated 16 through 2 investigated 32 for 3 the 5 coverage 4 newspaper 5 coverage 5 coverage 6 of 5 coverage 9 and 6 of 8 well 7 aging 8 well 9 and 11 terms 9 and 13 as 10 synonymous 11 terms 12 such 13 as 13 as 15 aging 14 active 15 aging 16 through 18 lens 17 the 18 lens 18 lens 19 of 19 of 27 and 20 the 26 framework 21 2002 25 policy 22 who 25 policy 23 active 25 policy 24 aging 25 policy 25 policy 26 framework 26 framework 27 and 27 and 31 charter 28 the 31 charter 29 2010 30 toronto 30 toronto 31 charter 32 for 34 activity 33 physical 34 activity as sources we used the following newspapers : china daily , the star ( malaysia ) , two uk newspapers ( the guardian , the times ) , a database of 300 canadian newspapers ( canadian newsstand ) and a us newspaper ( the new york times ) . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 used 0 ###LEFT-WALL### 8 : 1 as 2 sources 1 as 3 we 3 we 4 used 4 used 7 newspapers 5 the 6 following 5 the 7 newspapers 8 : 39 and 8 : 49 . 9 china 10 daily 10 daily 11 , 11 , 13 star 11 , 39 and 12 the 13 star 13 star 15 malaysia 13 star 20 newspapers 14 ( 15 malaysia 15 malaysia 16 ) 17 , 20 newspapers 18 two 20 newspapers 19 uk 20 newspapers 20 newspapers 23 guardian 20 newspapers 30 database 20 newspapers 38 ) 21 ( 23 guardian 22 the 23 guardian 23 guardian 26 times 23 guardian 28 , 24 , 26 times 25 the 26 times 26 times 27 ) 28 , 30 database 29 a 30 database 30 database 31 of 30 database 38 ) 31 of 34 newspapers 32 300 34 newspapers 33 canadian 34 newspapers 34 newspapers 37 newsstand 35 ( 37 newsstand 36 canadian 37 newsstand 37 newsstand 38 ) 39 and 42 newspaper 39 and 47 times 40 a 42 newspaper 41 us 42 newspaper 43 ( 47 times 44 the 47 times 45 new 46 york 46 york 47 times 47 times 48 ) the study found a total absence of mentioning of the two key documents and a low level of coverage of " active aging " and terms conveying similar content . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 found 0 ###LEFT-WALL### 30 . 1 the 2 study 2 study 3 found 3 found 14 and 3 found 17 level 3 found 25 and 4 a 6 absence 5 total 6 absence 6 absence 7 of 6 absence 14 and 7 of 8 mentioning 8 mentioning 9 of 9 of 13 documents 10 the 11 two 11 two 13 documents 12 key 13 documents 14 and 16 low 15 a 16 low 17 level 18 of 17 level 20 of 18 of 19 coverage 20 of 21 " 20 of 23 aging 22 active 23 aging 23 aging 24 " 25 and 26 terms 26 terms 27 conveying 27 conveying 29 content 28 similar 29 content it found further a lack of engagement with the issues raised in the two key documents and a low level of mentioning of [socially] disadvantages groups . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 2 found 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 27 . 1 it 2 found 2 found 3 further 2 found 5 lack 4 a 5 lack 5 lack 6 of 6 of 7 engagement 7 engagement 8 with 7 engagement 11 raised 8 with 10 issues 9 the 10 issues 11 raised 12 in 12 in 16 documents 13 the 14 two 14 two 16 documents 15 key 16 documents 17 and 20 level 17 and 26 groups 18 a 19 low 18 a 20 level 19 low 20 level 20 level 21 of 20 level 26 groups 21 of 22 mentioning 22 mentioning 23 of 23 of 25 disadvantages we posit that reading the newspapers we covered will not expose the reader to the two key documents and the issues linked to aging well including the need to increase physical activity . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 posit 0 ###LEFT-WALL### 33 . 1 we 2 posit 2 posit 3 that 3 that 4 reading 3 that 11 expose 4 reading 6 newspapers 4 reading 9 will 5 the 6 newspapers 6 newspapers 7 we 6 newspapers 8 covered 7 we 8 covered 9 will 10 not 9 will 11 expose 11 expose 19 and 12 the 13 reader 13 reader 14 to 13 reader 19 and 14 to 18 documents 15 the 16 two 16 two 18 documents 17 key 18 documents 19 and 21 issues 20 the 21 issues 21 issues 22 linked 21 issues 23 to 21 issues 26 including 23 to 24 aging 24 aging 25 well 26 including 28 need 27 the 28 need 28 need 29 to 28 need 30 increase 29 to 30 increase 30 increase 32 activity 31 physical 32 activity definitions of healthy ageing include survival to a specific age , being free of chronic diseases , autonomy in activities of daily living , wellbeing , good quality of life , high social participation , only mild cognitive or functional impairment , and little or no disability . 0 ###LEFT-WALL### 45 or 0 ###LEFT-WALL### 48 . 1 definitions 2 of 1 definitions 43 and 2 of 6 survival 3 healthy 4 ageing 4 ageing 6 survival 5 include 6 survival 6 survival 7 to 7 to 10 age 8 a 10 age 9 specific 10 age 10 age 12 being 11 , 12 being 12 being 13 free 12 being 42 , 13 free 14 of 14 of 16 diseases 15 chronic 16 diseases 16 diseases 18 autonomy 16 diseases 28 quality 17 , 18 autonomy 18 autonomy 19 in 18 autonomy 21 of 18 autonomy 26 , 19 in 20 activities 21 of 23 living 22 daily 23 living 23 living 25 wellbeing 24 , 25 wellbeing 25 wellbeing 26 , 26 , 28 quality 27 good 28 quality 28 quality 29 of 28 quality 41 impairment 28 quality 42 , 29 of 30 life 30 life 34 participation 31 , 34 participation 32 high 33 social 33 social 34 participation 34 participation 35 , 35 , 36 only 35 , 41 impairment 37 mild 41 impairment 38 cognitive 39 or 39 or 40 functional 39 or 41 impairment 41 impairment 42 , 43 and 44 little 43 and 45 or 45 or 47 disability 46 no 47 disability the working group epidemiology of ageing of the german association of epidemiology organized a workshop in 2012 with the aim to present different indicators used in german studies and to discuss their impact on health for an ageing middle - european population . 0 ###LEFT-WALL### 4 epidemiology 0 ###LEFT-WALL### 29 and 1 the 3 group 2 working 3 group 3 group 4 epidemiology 4 epidemiology 5 of 4 epidemiology 7 of 4 epidemiology 11 of 4 epidemiology 13 organized 5 of 6 ageing 7 of 10 association 8 the 10 association 9 german 10 association 11 of 12 epidemiology 13 organized 15 workshop 13 organized 16 in 13 organized 18 with 13 organized 21 to 14 a 15 workshop 16 in 17 2012 18 with 20 aim 19 the 20 aim 21 to 29 and 22 present 24 indicators 22 present 26 in 22 present 29 and 23 different 24 indicators 24 indicators 25 used 26 in 28 studies 27 german 28 studies 29 and 30 to 29 and 31 discuss 30 to 31 discuss 31 discuss 33 impact 32 their 33 impact 33 impact 34 on 33 impact 42 population 34 on 35 health 35 health 36 for 36 for 39 middle 37 an 39 middle 38 ageing 39 middle 40 - 42 population 41 european 42 population 42 population 43 . workshop presentations focused on prevalence of chronic diseases and multimorbidity , development of healthy life expectancy at the transition [to] [oldest] - age , physical activity , assessment of cognitive capability , and functioning and disability in old age . 0 ###LEFT-WALL### 35 and 0 ###LEFT-WALL### 40 . 1 workshop 2 presentations 2 presentations 3 focused 2 presentations 6 of 2 presentations 9 and 3 focused 4 on 4 on 5 prevalence 6 of 8 diseases 7 chronic 8 diseases 9 and 10 multimorbidity 9 and 12 development 9 and 23 age 9 and 33 and 11 , 12 development 12 development 13 of 12 development 17 at 12 development 22 - 13 of 16 expectancy 14 healthy 15 life 15 life 16 expectancy 17 at 19 transition 18 the 19 transition 22 - 23 age 23 age 26 activity 23 age 32 , 24 , 26 activity 25 physical 26 activity 26 activity 28 assessment 26 activity 32 , 27 , 28 assessment 28 assessment 29 of 28 assessment 32 , 29 of 31 capability 30 cognitive 31 capability 33 and 34 functioning 33 and 35 and 35 and 36 disability 35 and 37 in 37 in 39 age 38 old 39 age the communication describes the results regarding specific indicators for germany , and hereby contributes to the further development of a set of indicators for the assessment of healthy ageing . 0 ###LEFT-WALL### 2 communication 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 30 . 1 the 2 communication 2 communication 12 and 3 describes 5 results 3 describes 12 and 4 the 5 results 5 results 6 regarding 6 regarding 8 indicators 6 regarding 9 for 7 specific 8 indicators 9 for 10 germany 11 , 12 and 12 and 14 contributes 12 and 15 to 13 hereby 14 contributes 15 to 18 development 16 the 18 development 17 further 18 development 18 development 19 of 19 of 21 set 20 a 21 set 21 set 22 of 22 of 23 indicators 23 indicators 24 for 24 for 26 assessment 25 the 26 assessment 26 assessment 27 of 27 of 29 ageing 28 healthy 29 ageing background : chronic knee pain is still considered a fairly benign disease by many , an ['] unavoidable ['] consequence of ageing . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 5 pain 2 : 8 considered 3 chronic 4 knee 4 knee 5 pain 5 pain 6 is 6 is 8 considered 7 still 8 considered 8 considered 12 disease 8 considered 13 by 9 a 10 fairly 9 a 12 disease 10 fairly 11 benign 11 benign 12 disease 13 by 14 many 14 many 20 consequence 15 , 20 consequence 16 an 20 consequence 18 unavoidable 20 consequence 20 consequence 21 of 20 consequence 23 . 21 of 22 ageing this passive acceptance may be unnecessarily exposing older people to disability and serious co - morbidity . 0 ###LEFT-WALL### 3 acceptance 0 ###LEFT-WALL### 5 be 0 ###LEFT-WALL### 17 . 1 this 2 passive 2 passive 3 acceptance 3 acceptance 4 may 4 may 5 be 5 be 7 exposing 6 unnecessarily 7 exposing 7 exposing 9 people 7 exposing 10 to 8 older 9 people 10 to 12 and 11 disability 12 and 12 and 16 morbidity 13 serious 16 morbidity 14 co 15 - 14 co 16 morbidity the aim of this study was to determine the disease burden associated with chronic knee pain and the role of knee extensor strength as a modifiable risk factor . 0 ###LEFT-WALL### 2 aim 0 ###LEFT-WALL### 12 associated 0 ###LEFT-WALL### 29 . 1 the 2 aim 2 aim 3 of 2 aim 6 was 3 of 5 study 4 this 5 study 6 was 7 to 6 was 12 associated 7 to 8 determine 8 determine 11 burden 9 the 11 burden 10 disease 11 burden 12 associated 13 with 12 associated 24 as 13 with 17 and 14 chronic 15 knee 15 knee 16 pain 16 pain 17 and 17 and 19 role 17 and 20 of 18 the 19 role 20 of 23 strength 21 knee 23 strength 22 extensor 23 strength 24 as 28 factor 25 a 26 modifiable 25 a 28 factor 26 modifiable 28 factor 27 risk 28 factor methods : a longitudinal cohort study with 2 - [year] follow - up conducted among 1,587 [community] - dwelling men aged 70 years and [over] , 637 ( 40 % ) reported chronic knee pain . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 9 - 0 ###LEFT-WALL### 36 . 1 methods 2 : 2 : 6 study 3 a 6 study 4 longitudinal 5 cohort 5 cohort 6 study 6 study 7 with 7 with 8 2 9 - 11 follow 9 - 12 - 12 - 19 dwelling 12 - 21 aged 12 - 24 and 13 up 19 dwelling 14 conducted 15 among 14 conducted 18 - 14 conducted 19 dwelling 15 among 16 1,587 19 dwelling 20 men 19 dwelling 21 aged 21 aged 23 years 22 70 23 years 24 and 26 , 24 and 27 637 24 and 32 reported 27 637 30 % 27 637 32 reported 28 ( 30 % 29 40 30 % 30 % 31 ) 32 reported 35 pain 33 chronic 34 knee 34 knee 35 pain of the 950 ( 60 % ) men without knee pain at baseline , 768 ( 81 % ) returned for the [follow] [-] up assessment with 150 ( 20 % ) reporting incident chronic knee pain . 0 ###LEFT-WALL### 8 men 0 ###LEFT-WALL### 20 returned 0 ###LEFT-WALL### 38 . 1 of 3 950 1 of 7 ) 1 of 8 men 2 the 3 950 3 950 6 % 4 ( 6 % 5 60 6 % 6 % 7 ) 8 men 9 without 8 men 12 at 8 men 20 returned 9 without 11 pain 10 knee 11 pain 12 at 13 baseline 13 baseline 15 768 14 , 15 768 15 768 18 % 15 768 19 ) 16 ( 18 % 17 81 18 % 18 % 19 ) 20 returned 21 for 21 for 26 assessment 22 the 26 assessment 25 up 26 assessment 26 assessment 27 with 26 assessment 33 reporting 27 with 28 150 28 150 31 % 29 ( 31 % 30 20 31 % 31 % 32 ) 33 reporting 37 pain 34 incident 37 pain 35 chronic 36 knee 36 knee 37 pain men with incident knee pain at the 2 [-] year follow - up assessment demonstrated greater increases in these measures of disease burden and greater decreases in muscle strength and mass , compared with those without incident chronic knee pain . 0 ###LEFT-WALL### 1 men 0 ###LEFT-WALL### 11 follow 1 men 2 with 1 men 6 at 1 men 11 follow 2 with 5 pain 3 incident 5 pain 4 knee 5 pain 6 at 10 year 7 the 10 year 8 2 10 year 11 follow 13 up 11 follow 33 compared 12 - 13 up 13 up 17 increases 13 up 32 , 14 assessment 15 demonstrated 15 demonstrated 17 increases 16 greater 17 increases 17 increases 18 in 17 increases 21 of 18 in 20 measures 19 these 20 measures 21 of 30 and 22 disease 23 burden 23 burden 24 and 24 and 26 decreases 24 and 27 in 24 and 30 and 25 greater 26 decreases 27 in 29 strength 28 muscle 29 strength 30 and 31 mass 32 , 33 compared 33 compared 34 with 33 compared 41 . 34 with 35 those 35 those 36 without 36 without 40 pain 37 incident 40 pain 38 chronic 39 knee 39 knee 40 pain obesity , high co - morbidity burden , back pain , higher levels of physical activity or low knee extensor strength were all significant risk factors for incident knee pain . 0 ###LEFT-WALL### 17 or 0 ###LEFT-WALL### 22 were 0 ###LEFT-WALL### 31 . 1 obesity 2 , 2 , 13 levels 2 , 17 or 3 high 13 levels 4 co 7 burden 4 co 11 , 4 co 13 levels 5 - 7 burden 6 morbidity 7 burden 7 burden 10 pain 7 burden 11 , 8 , 10 pain 9 back 10 pain 10 pain 11 , 12 higher 13 levels 13 levels 14 of 14 of 16 activity 15 physical 16 activity 17 or 21 strength 17 or 22 were 18 low 21 strength 19 knee 21 strength 20 extensor 21 strength 22 were 26 factors 23 all 26 factors 24 significant 26 factors 25 risk 26 factors 26 factors 27 for 27 for 30 pain 28 incident 29 knee 29 knee 30 pain conclusion : prevention of chronic knee pain may reduce a considerable burden of mobility disability and increased risk of serious co - morbidity among older men . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 27 . 1 conclusion 2 : 2 : 3 prevention 3 prevention 4 of 4 of 7 pain 5 chronic 6 knee 6 knee 7 pain 7 pain 16 and 7 pain 19 of 8 may 9 reduce 8 may 16 and 9 reduce 12 burden 10 a 11 considerable 10 a 12 burden 11 considerable 12 burden 12 burden 13 of 13 of 15 disability 14 mobility 15 disability 16 and 17 increased 17 increased 18 risk 19 of 23 morbidity 20 serious 23 morbidity 21 co 22 - 21 co 23 morbidity 23 morbidity 24 among 24 among 26 men 25 older 26 men resveratrol , a polyphenolic compound , is [a] naturally occurring [phytochemical] and is found in a variety of plants , including food such as grapes , berries and peanuts . 0 ###LEFT-WALL### 1 resveratrol 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 30 . 1 resveratrol 5 compound 1 resveratrol 12 and 2 , 5 compound 3 a 4 polyphenolic 3 a 5 compound 4 polyphenolic 5 compound 5 compound 6 , 7 is 10 occurring 7 is 12 and 9 naturally 10 occurring 12 and 13 is 13 is 14 found 14 found 15 in 14 found 21 including 14 found 28 and 15 in 17 variety 16 a 17 variety 17 variety 18 of 18 of 19 plants 20 , 21 including 21 including 22 food 21 including 24 as 21 including 26 , 23 such 24 as 24 as 25 grapes 27 berries 28 and 28 and 29 peanuts it has gained much attention for its potential anticancer activity against various types of human cancer . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 3 gained 0 ###LEFT-WALL### 17 . 1 it 2 has 2 has 3 gained 3 gained 5 attention 3 gained 11 against 4 much 5 attention 5 attention 6 for 6 for 10 activity 7 its 10 activity 8 potential 10 activity 9 anticancer 10 activity 11 against 16 cancer 12 various 13 types 13 types 14 of 13 types 16 cancer 14 of 16 cancer 15 human 16 cancer however , the usefulness of resveratrol as a chemotherapeutic agent is limited by its photosensitivity and metabolic instability . 0 ###LEFT-WALL### 4 usefulness 0 ###LEFT-WALL### 11 is 0 ###LEFT-WALL### 19 . 1 however 2 , 1 however 4 usefulness 3 the 4 usefulness 4 usefulness 5 of 4 usefulness 11 is 5 of 6 resveratrol 6 resveratrol 7 as 7 as 10 agent 8 a 9 chemotherapeutic 8 a 10 agent 9 chemotherapeutic 10 agent 11 is 12 limited 12 limited 13 by 13 by 16 and 14 its 15 photosensitivity 15 photosensitivity 16 and 16 and 18 instability 17 metabolic 18 instability in this study the effects of a synthetic analogue of resveratrol , hs - 1793 , on the proliferation and apoptotic cell death were investigated using mcf - 7 ( wild - type p53 ) and mda - mb - 231 ( mutant p53 ) human breast cancer cells . 0 ###LEFT-WALL### 20 and 0 ###LEFT-WALL### 25 investigated 0 ###LEFT-WALL### 50 . 1 in 3 study 1 in 20 and 2 this 3 study 4 the 5 effects 5 effects 6 of 5 effects 12 , 6 of 9 analogue 7 a 9 analogue 8 synthetic 9 analogue 9 analogue 10 of 10 of 11 resveratrol 12 , 13 hs 12 , 20 and 13 hs 15 1793 13 hs 17 on 14 - 15 1793 15 1793 16 , 17 on 19 proliferation 18 the 19 proliferation 20 and 23 death 20 and 24 were 21 apoptotic 22 cell 22 cell 23 death 24 were 25 investigated 25 investigated 26 using 26 using 49 cells 27 mcf 29 7 27 mcf 36 and 28 - 29 7 29 7 34 p53 29 7 35 ) 30 ( 34 p53 31 wild 32 - 31 wild 33 type 33 type 34 p53 34 p53 35 ) 36 and 37 mda 36 and 38 - 36 and 39 mb 36 and 46 human 38 - 39 mb 39 mb 41 231 39 mb 45 ) 40 - 41 231 41 231 44 p53 41 231 45 ) 42 ( 44 p53 43 mutant 44 p53 44 p53 45 ) 46 human 49 cells 47 breast 48 cancer 48 cancer 49 cells hs - 1793 inhibited cell growth and induced apoptotic cell death in a concentration - dependent manner . 0 ###LEFT-WALL### 3 1793 0 ###LEFT-WALL### 7 and 0 ###LEFT-WALL### 15 - 1 hs 2 - 1 hs 3 1793 3 1793 7 and 4 inhibited 6 growth 4 inhibited 7 and 5 cell 6 growth 7 and 8 induced 8 induced 11 death 8 induced 12 in 9 apoptotic 10 cell 10 cell 11 death 12 in 14 concentration 13 a 14 concentration 15 - 17 manner 15 - 18 . 16 dependent 17 manner the induction of apoptosis was determined by morphological changes , [cleavage] of [poly] [(] adp - ribose ) poly - merase , alteration of bax/bcl - 2 expression ratio [and] caspase activities . 0 ###LEFT-WALL### 2 induction 0 ###LEFT-WALL### 5 was 0 ###LEFT-WALL### 20 - 1 the 2 induction 2 induction 3 of 2 induction 5 was 3 of 4 apoptosis 5 was 6 determined 6 determined 7 by 6 determined 19 poly 7 by 9 changes 8 morphological 9 changes 9 changes 12 of 10 , 12 of 12 of 15 adp 12 of 18 ) 15 adp 17 ribose 16 - 17 ribose 17 ribose 18 ) 20 - 21 merase 20 - 26 - 21 merase 23 alteration 22 , 23 alteration 23 alteration 24 of 23 alteration 26 - 24 of 25 bax/bcl 26 - 32 activities 26 - 33 . 27 2 32 activities 28 expression 32 activities 29 ratio 32 activities 31 caspase 32 activities flow cytometric analysis revealed that hs - 1793 induced g2/m arrest in the cell cycle progression in both types of cells . 0 ###LEFT-WALL### 3 analysis 0 ###LEFT-WALL### 4 revealed 0 ###LEFT-WALL### 7 - 0 ###LEFT-WALL### 22 . 1 flow 3 analysis 2 cytometric 3 analysis 3 analysis 4 revealed 4 revealed 6 hs 5 that 6 hs 7 - 8 1793 7 - 9 induced 8 1793 9 induced 9 induced 11 arrest 9 induced 17 in 10 g2/m 11 arrest 11 arrest 12 in 12 in 16 progression 13 the 16 progression 14 cell 15 cycle 15 cycle 16 progression 17 in 21 cells 18 both 19 types 19 types 20 of 19 types 21 cells 20 of 21 cells [of] note , hs - 1793 induced p53/p21waf1/cip1 - dependent apoptosis in mcf - 7 cells , whereas it exhibited p53 - independent apoptosis in mda - mb - 231 cells . 0 ###LEFT-WALL### 2 note 0 ###LEFT-WALL### 3 , 0 ###LEFT-WALL### 20 exhibited 3 , 6 1793 3 , 7 induced 4 hs 5 - 4 hs 6 1793 6 1793 7 induced 7 induced 11 apoptosis 7 induced 12 in 7 induced 18 whereas 8 p53/p21waf1/cip1 9 - 8 p53/p21waf1/cip1 11 apoptosis 10 dependent 11 apoptosis 12 in 13 mcf 13 mcf 16 cells 14 - 16 cells 15 7 16 cells 16 cells 17 , 18 whereas 19 it 19 it 20 exhibited 20 exhibited 24 apoptosis 21 p53 22 - 21 p53 23 independent 23 independent 24 apoptosis 24 apoptosis 25 in 24 apoptosis 28 mb 25 in 26 mda 27 - 28 mb 28 mb 31 cells 28 mb 32 . 29 - 31 cells 30 231 31 cells 31 cells 32 . furthermore , hs - 1793 showed more potent anticancer effects in several aspects compared to resveratrol in mcf - 7 and mda - mb - 231 cells . 0 ###LEFT-WALL### 5 1793 0 ###LEFT-WALL### 6 showed 0 ###LEFT-WALL### 28 . 1 furthermore 2 , 1 furthermore 5 1793 3 hs 4 - 3 hs 5 1793 5 1793 6 showed 6 showed 10 effects 6 showed 11 in 6 showed 13 aspects 6 showed 14 compared 7 more 8 potent 8 potent 9 anticancer 9 anticancer 10 effects 11 in 12 several 13 aspects 14 compared 14 compared 15 to 14 compared 17 in 14 compared 27 cells 15 to 16 resveratrol 17 in 18 mcf 18 mcf 22 mda 19 - 22 mda 20 7 21 and 21 and 22 mda 22 mda 24 mb 22 mda 25 - 23 - 24 mb 24 mb 25 - 26 231 27 cells thus , these findings suggest that hs - 1793 has potential as a candidate chemotherapeutic agent against human breast cancer . 0 ###LEFT-WALL### 4 findings 0 ###LEFT-WALL### 5 suggest 0 ###LEFT-WALL### 8 - 1 thus 2 , 1 thus 4 findings 3 these 4 findings 4 findings 5 suggest 5 suggest 7 hs 6 that 7 hs 8 - 9 1793 8 - 10 has 8 - 21 . 9 1793 10 has 10 has 11 potential 10 has 12 as 10 has 17 against 12 as 16 agent 13 a 16 agent 14 candidate 16 agent 15 chemotherapeutic 16 agent 17 against 20 cancer 18 human 19 breast 19 breast 20 cancer purpose of review : to underscore recent clinical studies , which evaluate the association between dietary protein and bone health . 0 ###LEFT-WALL### 3 review 0 ###LEFT-WALL### 4 : 1 purpose 2 of 2 of 3 review 4 : 5 to 4 : 6 underscore 4 : 10 , 4 : 21 . 5 to 6 underscore 6 underscore 9 studies 7 recent 9 studies 8 clinical 9 studies 10 , 11 which 10 , 18 and 11 which 18 and 12 evaluate 14 association 12 evaluate 15 between 12 evaluate 18 and 13 the 14 association 15 between 17 protein 16 dietary 17 protein 18 and 19 bone 18 and 20 health recent findings : epidemiologic studies show greater protein intake to be beneficial to bone health in adults . 0 ###LEFT-WALL### 2 findings 0 ###LEFT-WALL### 3 : 1 recent 2 findings 3 : 4 epidemiologic 3 : 5 studies 3 : 18 . 4 epidemiologic 5 studies 5 studies 9 intake 5 studies 10 to 6 show 9 intake 7 greater 8 protein 8 protein 9 intake 10 to 11 be 11 be 12 beneficial 12 beneficial 13 to 13 to 15 health 14 bone 15 health 15 health 16 in 16 in 17 adults in addition , randomized controlled trials show that protein 's positive effect on bone health is augmented by increased calcium intake . 0 ###LEFT-WALL### 6 trials 0 ###LEFT-WALL### 7 show 0 ###LEFT-WALL### 22 . 1 in 2 addition 1 in 3 , 1 in 6 trials 4 randomized 6 trials 5 controlled 6 trials 6 trials 7 show 7 show 8 that 8 that 12 effect 8 that 17 augmented 9 protein 10 's 10 's 12 effect 11 positive 12 effect 12 effect 13 on 12 effect 16 is 13 on 15 health 14 bone 15 health 16 is 17 augmented 17 augmented 18 by 18 by 21 intake 19 increased 20 calcium 20 calcium 21 intake the relation between dietary protein and fracture risk is unclear . 0 ###LEFT-WALL### 2 relation 0 ###LEFT-WALL### 9 is 0 ###LEFT-WALL### 11 . 1 the 2 relation 2 relation 3 between 2 relation 9 is 3 between 6 and 4 dietary 5 protein 5 protein 6 and 6 and 8 risk 7 fracture 8 risk 9 is 10 unclear dietary protein may positively impact bone health by increasing muscle [mass] , increasing calcium absorption , suppressing parathyroid hormone , and augmenting insulin - like growth factor 1 production [;] but the effects of other factors that contribute to this association , such as dietary protein dose and timing response , require further [research] . 0 ###LEFT-WALL### 2 protein 0 ###LEFT-WALL### 5 impact 1 dietary 2 protein 2 protein 3 may 3 may 5 impact 4 positively 5 impact 5 impact 7 health 6 bone 7 health 7 health 8 by 7 health 17 suppressing 8 by 10 muscle 9 increasing 10 muscle 10 muscle 15 absorption 12 , 15 absorption 13 increasing 15 absorption 14 calcium 15 absorption 15 absorption 16 , 17 suppressing 29 production 18 parathyroid 29 production 19 hormone 21 and 20 , 21 and 21 and 23 insulin 21 and 24 - 21 and 25 like 21 and 29 production 22 augmenting 23 insulin 25 like 27 factor 26 growth 27 factor 27 factor 28 1 29 production 31 but 31 but 33 effects 32 the 33 effects 33 effects 34 of 33 effects 39 to 34 of 36 factors 35 other 36 factors 36 factors 37 that 36 factors 38 contribute 37 that 38 contribute 39 to 41 association 40 this 41 association 41 association 46 protein 42 , 46 protein 43 such 46 protein 44 as 45 dietary 45 dietary 46 protein 46 protein 48 and 46 protein 52 require 46 protein 55 . 47 dose 48 and 48 and 50 response 48 and 51 , 48 and 52 require 49 timing 50 response 52 require 53 further summary : the positive effects of protein intake on bone health may only be beneficial under conditions of adequate calcium intake . 0 ###LEFT-WALL### 1 summary 0 ###LEFT-WALL### 2 : 2 : 5 effects 2 : 14 be 2 : 22 . 3 the 5 effects 4 positive 5 effects 5 effects 6 of 5 effects 12 may 6 of 8 intake 7 protein 8 intake 8 intake 9 on 9 on 11 health 10 bone 11 health 12 may 14 be 13 only 14 be 14 be 15 beneficial 15 beneficial 16 under 16 under 17 conditions 17 conditions 18 of 18 of 21 intake 19 adequate 20 calcium 20 calcium 21 intake dietary protein 's relation with fracture risk requires further investigation . 0 ###LEFT-WALL### 4 relation 0 ###LEFT-WALL### 8 requires 0 ###LEFT-WALL### 11 . 1 dietary 2 protein 2 protein 3 's 3 's 4 relation 4 relation 5 with 4 relation 8 requires 5 with 7 risk 6 fracture 7 risk 8 requires 10 investigation 9 further 10 investigation purpose of review : to examine the role of two nutritional factors implicated in the healthy aging of the okinawans : caloric restriction [;] and traditional foods with potential caloric [restriction] - mimetic properties . 0 ###LEFT-WALL### 3 review 0 ###LEFT-WALL### 4 : 0 ###LEFT-WALL### 35 . 1 purpose 2 of 2 of 3 review 4 : 5 to 4 : 21 : 5 to 6 examine 5 to 21 : 6 examine 8 role 6 examine 14 in 7 the 8 role 8 role 9 of 9 of 12 factors 10 two 12 factors 11 nutritional 12 factors 12 factors 13 implicated 14 in 17 aging 15 the 17 aging 16 healthy 17 aging 17 aging 18 of 18 of 20 okinawans 19 the 20 okinawans 21 : 25 and 22 caloric 23 restriction 23 restriction 25 and 25 and 27 foods 26 traditional 27 foods 27 foods 28 with 28 with 34 properties 29 potential 34 properties 30 caloric 32 - 30 caloric 34 properties 33 mimetic 34 properties recent findings : caloric restriction is a research priority for the us national institute on aging . 0 ###LEFT-WALL### 2 findings 0 ###LEFT-WALL### 3 : 1 recent 2 findings 3 : 5 restriction 3 : 6 is 3 : 17 . 4 caloric 5 restriction 5 restriction 6 is 6 is 9 priority 7 a 8 research 7 a 9 priority 8 research 9 priority 9 priority 10 for 10 for 14 institute 11 the 14 institute 12 us 13 national 13 national 14 institute 14 institute 15 on 15 on 16 aging however , little is known regarding health effects in humans . 0 ###LEFT-WALL### 3 little 0 ###LEFT-WALL### 4 is 0 ###LEFT-WALL### 11 . 1 however 2 , 1 however 3 little 3 little 4 is 4 is 8 effects 5 known 8 effects 6 regarding 8 effects 7 health 8 effects 8 effects 9 in 9 in 10 humans some caloric restriction - related outcomes , [such] as cause - specific mortality and lifespan , are not practical [for] human clinical trials . 0 ###LEFT-WALL### 3 restriction 0 ###LEFT-WALL### 17 are 0 ###LEFT-WALL### 24 . 1 some 3 restriction 2 caloric 3 restriction 3 restriction 6 outcomes 3 restriction 10 cause 3 restriction 17 are 4 - 6 outcomes 5 related 6 outcomes 6 outcomes 7 , 7 , 10 cause 9 as 10 cause 10 cause 11 - 10 cause 14 and 10 cause 16 , 12 specific 13 mortality 13 mortality 14 and 14 and 15 lifespan 17 are 18 not 17 are 23 trials 19 practical 23 trials 21 human 23 trials 22 clinical 23 trials therefore , epidemiological data on older okinawans , who experienced a caloric restriction - like [diet] [for] close to half their lives , are of special interest . 0 ###LEFT-WALL### 4 data 0 ###LEFT-WALL### 24 are 0 ###LEFT-WALL### 28 . 1 therefore 2 , 1 therefore 4 data 3 epidemiological 4 data 4 data 5 on 4 data 24 are 5 on 7 okinawans 6 older 7 okinawans 7 okinawans 9 who 8 , 9 who 9 who 10 experienced 9 who 23 , 10 experienced 13 restriction 11 a 12 caloric 11 a 13 restriction 12 caloric 13 restriction 13 restriction 15 like 14 - 15 like 15 like 19 to 15 like 23 , 18 close 19 to 19 to 20 half 20 half 21 their 20 half 22 lives 21 their 22 lives 24 are 25 of 25 of 27 interest 26 special 27 interest the nutritional data support mild caloric [restriction] ( 10 - 15 % ) and high consumption of foods that may mimic the biological effects [of] caloric restriction , including sweet potatoes , marine - based carotenoid - rich foods , and turmeric . 0 ###LEFT-WALL### 3 data 0 ###LEFT-WALL### 4 support 0 ###LEFT-WALL### 32 , 1 the 3 data 2 nutritional 3 data 3 data 4 support 4 support 16 consumption 4 support 29 including 5 mild 16 consumption 6 caloric 10 - 6 caloric 14 and 8 ( 10 - 9 10 10 - 10 - 12 % 10 - 13 ) 11 15 12 % 14 and 15 high 14 and 16 consumption 16 consumption 17 of 17 of 18 foods 18 foods 19 that 18 foods 20 may 19 that 20 may 20 may 21 mimic 21 mimic 27 restriction 22 the 27 restriction 23 biological 24 effects 24 effects 27 restriction 26 caloric 27 restriction 28 , 29 including 29 including 31 potatoes 29 including 32 , 30 sweet 31 potatoes 32 , 41 and 33 marine 34 - 33 marine 39 foods 35 based 39 foods 36 carotenoid 37 - 36 carotenoid 39 foods 38 rich 39 foods 39 foods 41 and 40 , 41 and 41 and 42 turmeric 41 and 43 . phenotypic evidence is consistent with caloric restriction [(] including short stature , low body weight , and lean bmi ) , less age - related chronic disease ( including cardiovascular diseases , cancer , and dementia ) , and longer lifespan ( mean and maximum ) . 0 ###LEFT-WALL### 1 phenotypic 0 ###LEFT-WALL### 3 is 0 ###LEFT-WALL### 25 related 0 ###LEFT-WALL### 32 , 0 ###LEFT-WALL### 47 . 1 phenotypic 3 is 2 evidence 3 is 3 is 4 consistent 4 consistent 5 with 5 with 17 and 6 caloric 7 restriction 7 restriction 9 including 7 restriction 17 and 9 including 11 stature 10 short 11 stature 11 stature 15 weight 12 , 15 weight 13 low 15 weight 14 body 15 weight 15 weight 16 , 17 and 19 bmi 17 and 20 ) 17 and 23 age 18 lean 19 bmi 21 , 23 age 22 less 23 age 23 age 24 - 24 - 25 related 25 related 27 disease 26 chronic 27 disease 27 disease 29 including 28 ( 29 including 29 including 31 diseases 29 including 32 , 30 cardiovascular 31 diseases 32 , 39 and 33 cancer 35 and 34 , 35 and 35 and 36 dementia 35 and 37 ) 35 and 39 and 38 , 39 and 39 and 41 lifespan 39 and 44 and 40 longer 41 lifespan 42 ( 44 and 43 mean 44 and 44 and 45 maximum 44 and 46 ) summary : both caloric restriction and traditional okinawan functional foods with caloric [restriction] - mimetic properties likely had roles in the extended healthspan and lifespan of the okinawans . 0 ###LEFT-WALL### 1 summary 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 29 . 1 summary 2 : 2 : 19 roles 2 : 20 in 3 both 19 roles 4 caloric 5 restriction 5 restriction 6 and 6 and 8 okinawan 6 and 10 foods 6 and 18 had 6 and 19 roles 7 traditional 8 okinawan 9 functional 10 foods 10 foods 11 with 10 foods 18 had 11 with 16 properties 12 caloric 14 - 12 caloric 16 properties 15 mimetic 16 properties 17 likely 18 had 20 in 24 and 21 the 23 healthspan 22 extended 23 healthspan 23 healthspan 24 and 24 and 25 lifespan 25 lifespan 26 of 26 of 28 okinawans 27 the 28 okinawans more research is needed on health consequences of caloric restriction and foods with caloric [restriction] - mimetic properties to identify possible nutritional interventions for healthy aging . 0 ###LEFT-WALL### 2 research 0 ###LEFT-WALL### 20 identify 0 ###LEFT-WALL### 27 . 1 more 2 research 2 research 3 is 3 is 4 needed 4 needed 5 on 4 needed 13 with 4 needed 19 to 5 on 7 consequences 6 health 7 consequences 7 consequences 8 of 8 of 11 and 9 caloric 10 restriction 10 restriction 11 and 11 and 12 foods 13 with 18 properties 14 caloric 16 - 14 caloric 18 properties 17 mimetic 18 properties 19 to 20 identify 20 identify 23 interventions 21 possible 23 interventions 22 nutritional 23 interventions 23 interventions 24 for 24 for 26 aging 25 healthy 26 aging planning defined as the predetermination of a sequence of actions towards some goal is crucial for complex problem solving . 0 ###LEFT-WALL### 1 planning 0 ###LEFT-WALL### 14 is 0 ###LEFT-WALL### 20 . 1 planning 2 defined 1 planning 14 is 2 defined 3 as 2 defined 11 towards 3 as 5 predetermination 4 the 5 predetermination 5 predetermination 6 of 6 of 8 sequence 7 a 8 sequence 8 sequence 9 of 9 of 10 actions 11 towards 13 goal 12 some 13 goal 14 is 15 crucial 15 crucial 16 for 16 for 19 solving 17 complex 19 solving 18 problem 19 solving to shed light on the evolution of executive functions , we investigated the ontogenetic and phylogenetic origins of planning . 0 ###LEFT-WALL### 1 to 0 ###LEFT-WALL### 2 shed 0 ###LEFT-WALL### 10 , 0 ###LEFT-WALL### 20 . 1 to 2 shed 2 shed 3 light 2 shed 4 on 4 on 6 evolution 5 the 6 evolution 6 evolution 7 of 7 of 9 functions 8 executive 9 functions 10 , 11 we 10 , 12 investigated 11 we 12 investigated 12 investigated 17 origins 13 the 17 origins 14 ontogenetic 15 and 15 and 16 phylogenetic 15 and 17 origins 17 origins 18 of 18 of 19 planning therefore , we presented all four great apes species ( n=12 ) as well as 4 [-] and 5 - year [-] old human preschoolers ( n=24 ) with a vertical maze task . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 presented 0 ###LEFT-WALL### 34 . 1 therefore 2 , 1 therefore 3 we 3 we 4 presented 4 presented 9 species 4 presented 14 well 4 presented 15 as 5 all 6 four 6 four 9 species 7 great 8 apes 8 apes 9 species 9 species 11 n=12 10 ( 11 n=12 11 n=12 12 ) 13 as 14 well 15 as 18 and 15 as 29 with 16 4 18 and 18 and 19 5 18 and 25 preschoolers 20 - 25 preschoolers 21 year 23 old 23 old 25 preschoolers 24 human 25 preschoolers 25 preschoolers 27 n=24 25 preschoolers 28 ) 26 ( 27 n=24 27 n=24 28 ) 29 with 33 task 30 a 31 vertical 30 a 33 task 31 vertical 32 maze 32 maze 33 task to gain a reward placed on the uppermost level of the maze , subjects had to move the reward to the bottom through open gaps situated at each level of the maze . 0 ###LEFT-WALL### 1 to 0 ###LEFT-WALL### 2 gain 0 ###LEFT-WALL### 13 , 0 ###LEFT-WALL### 33 . 1 to 2 gain 2 gain 4 reward 2 gain 6 on 3 a 4 reward 4 reward 5 placed 6 on 9 level 7 the 9 level 8 uppermost 9 level 9 level 10 of 10 of 12 maze 11 the 12 maze 13 , 14 subjects 13 , 15 had 14 subjects 15 had 15 had 16 to 15 had 17 move 16 to 17 move 17 move 19 reward 17 move 20 to 17 move 23 through 18 the 19 reward 20 to 22 bottom 21 the 22 bottom 23 through 25 gaps 24 open 25 gaps 25 gaps 26 situated 25 gaps 30 of 26 situated 27 at 27 at 29 level 28 each 29 level 30 of 32 maze 31 the 32 maze in total , there were ten gaps located over three of the maze 's levels , and free passage through these gaps could be flexibly blocked using multiple traps . 0 ###LEFT-WALL### 4 there 0 ###LEFT-WALL### 5 were 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 30 . 1 in 2 total 2 total 3 , 2 total 4 there 4 there 5 were 5 were 7 gaps 5 were 9 over 6 ten 7 gaps 7 gaps 8 located 9 over 10 three 10 three 11 of 11 of 15 levels 12 the 13 maze 13 maze 14 's 14 's 15 levels 16 , 17 and 17 and 19 passage 17 and 26 blocked 18 free 19 passage 19 passage 20 through 19 passage 23 could 20 through 22 gaps 21 these 22 gaps 23 could 24 be 24 be 25 flexibly 24 be 26 blocked 26 blocked 27 using 27 using 29 traps 28 multiple 29 traps due to the decision tree design of the maze , the subjects had to plan their actions depending on the trap configuration up to two steps ahead to successfully retrieve the reward . 0 ###LEFT-WALL### 5 tree 0 ###LEFT-WALL### 33 . 1 due 2 to 2 to 4 decision 2 to 5 tree 3 the 4 decision 5 tree 6 design 5 tree 19 on 6 design 7 of 6 design 18 depending 7 of 9 maze 8 the 9 maze 10 , 18 depending 11 the 12 subjects 12 subjects 13 had 13 had 14 to 13 had 15 plan 14 to 15 plan 15 plan 17 actions 15 plan 18 depending 16 their 17 actions 17 actions 18 depending 19 on 22 configuration 20 the 22 configuration 21 trap 22 configuration 22 configuration 23 up 23 up 24 to 23 up 28 to 23 up 30 retrieve 24 to 26 steps 25 two 26 steps 26 steps 27 ahead 28 to 30 retrieve 29 successfully 30 retrieve 30 retrieve 32 reward 31 the 32 reward we found that [(] 1 [ )(our measure of planning was negatively correlated with age in nonhuman apes , [(] 2 [ )(younger apes as well as 5 - year [-] old children planned their moves up to two steps ahead whereas 4 [-] year [-] olds were limited to plan one step ahead , and [(] 3 [ )(similar performance but different underlying limitations between apes and children . 1 we 2 found 2 found 3 that 2 found 5 1 5 1 10 planning 5 1 11 was 5 1 13 correlated 5 1 14 with 7 )(our 8 measure 8 measure 9 of 8 measure 10 planning 9 of 10 planning 10 planning 11 was 12 negatively 13 correlated 14 with 15 age 15 age 16 in 16 in 18 apes 17 nonhuman 18 apes 18 apes 29 - 19 , 29 - 21 2 24 apes 23 )(younger 24 apes 24 apes 25 as 24 apes 27 as 24 apes 29 - 25 as 26 well 27 as 28 5 29 - 33 children 30 year 32 old 32 old 33 children 33 children 34 planned 33 children 36 moves 33 children 37 up 35 their 36 moves 36 moves 37 up 37 up 38 to 37 up 41 ahead 37 up 42 whereas 38 to 40 steps 39 two 40 steps 42 whereas 47 olds 42 whereas 51 plan 43 4 47 olds 45 year 47 olds 47 olds 48 were 48 were 49 limited 49 limited 50 to 49 limited 51 plan 50 to 51 plan 51 plan 56 and 52 one 53 step 53 step 54 ahead 53 step 56 and 55 , 56 and 56 and 65 limitations 58 3 61 performance 60 )(similar 61 performance 61 performance 62 but 62 but 63 different 62 but 65 limitations 64 underlying 65 limitations 65 limitations 66 between 66 between 68 and 67 apes 68 and 68 and 69 children 68 and 70 . namely , while all species of nonhuman apes were limited by a lack of motor control , human children exhibited a shortage in shifting their attention across a sequence of subgoals . 0 ###LEFT-WALL### 19 children 0 ###LEFT-WALL### 20 exhibited 0 ###LEFT-WALL### 32 . 1 namely 19 children 2 , 3 while 3 while 5 species 3 while 9 were 3 while 17 , 3 while 19 children 4 all 5 species 5 species 6 of 5 species 9 were 6 of 8 apes 7 nonhuman 8 apes 9 were 10 limited 10 limited 11 by 11 by 13 lack 12 a 13 lack 13 lack 14 of 14 of 16 control 15 motor 16 control 18 human 19 children 19 children 20 exhibited 20 exhibited 22 shortage 20 exhibited 23 in 20 exhibited 27 across 21 a 22 shortage 23 in 24 shifting 24 shifting 26 attention 25 their 26 attention 27 across 29 sequence 28 a 29 sequence 29 sequence 30 of 30 of 31 subgoals once a backwater in medical sciences [,] aging research has emerged and now threatens to take the forefront . 0 ###LEFT-WALL### 3 backwater 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 19 . 1 once 3 backwater 2 a 3 backwater 3 backwater 4 in 3 backwater 10 has 4 in 6 sciences 5 medical 6 sciences 6 sciences 8 aging 8 aging 9 research 10 has 12 and 11 emerged 12 and 12 and 14 threatens 13 now 14 threatens 14 threatens 15 to 14 threatens 16 take 15 to 16 take 16 take 18 forefront 17 the 18 forefront this dramatic change of stature is driven from 3 major events . 0 ###LEFT-WALL### 3 change 0 ###LEFT-WALL### 7 driven 0 ###LEFT-WALL### 12 . 1 this 2 dramatic 2 dramatic 3 change 3 change 4 of 3 change 6 is 4 of 5 stature 6 is 7 driven 7 driven 8 from 8 from 11 events 9 3 11 events 10 major 11 events first [and] foremost , the world is rapidly getting old . 0 ###LEFT-WALL### 6 world 0 ###LEFT-WALL### 7 is 0 ###LEFT-WALL### 11 . 1 first 3 foremost 3 foremost 4 , 3 foremost 6 world 5 the 6 world 6 world 7 is 7 is 9 getting 8 rapidly 9 getting 9 getting 10 old never before have we lived in a demographic environment like today , and the trends will continue such that 20 % percent of the global population of 9 billion will be over the age of 60 by 2050 . 0 ###LEFT-WALL### 1 never 0 ###LEFT-WALL### 5 lived 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 39 . 1 never 2 before 1 never 3 have 3 have 4 we 3 have 5 lived 5 lived 6 in 5 lived 10 like 6 in 9 environment 7 a 8 demographic 7 a 9 environment 8 demographic 9 environment 10 like 11 today 12 , 13 and 13 and 15 trends 13 and 17 continue 14 the 15 trends 15 trends 16 will 16 will 17 continue 17 continue 19 that 17 continue 32 over 18 such 19 that 19 that 22 percent 19 that 31 be 20 20 22 percent 21 % 22 percent 22 percent 23 of 22 percent 27 of 22 percent 30 will 23 of 26 population 24 the 26 population 25 global 26 population 27 of 29 billion 28 9 29 billion 30 will 31 be 32 over 34 age 33 the 34 age 34 age 35 of 35 of 36 60 36 60 37 by 37 by 38 2050 given current trends of sharply increasing chronic disease [incidence] , economic disaster from the impending silver tsunami may be ahead . 0 ###LEFT-WALL### 12 disaster 0 ###LEFT-WALL### 19 be 0 ###LEFT-WALL### 21 . 1 given 3 trends 1 given 10 , 1 given 12 disaster 2 current 3 trends 3 trends 4 of 4 of 6 increasing 5 sharply 6 increasing 6 increasing 8 disease 7 chronic 8 disease 11 economic 12 disaster 12 disaster 13 from 12 disaster 18 may 13 from 17 tsunami 14 the 17 tsunami 15 impending 17 tsunami 16 silver 17 tsunami 18 may 19 be 19 be 20 ahead a second major driver on the rise is the dramatic progress that aging research has made using invertebrate models such as worms , flies , and yeast . 0 ###LEFT-WALL### 4 driver 0 ###LEFT-WALL### 8 is 0 ###LEFT-WALL### 28 . 1 a 4 driver 2 second 4 driver 3 major 4 driver 4 driver 5 on 4 driver 8 is 5 on 7 rise 6 the 7 rise 8 is 11 progress 9 the 11 progress 10 dramatic 11 progress 11 progress 12 that 11 progress 16 made 12 that 14 research 12 that 16 made 13 aging 14 research 14 research 15 has 15 has 16 made 16 made 17 using 17 using 19 models 18 invertebrate 19 models 19 models 21 as 20 such 21 as 21 as 26 and 22 worms 23 , 23 , 24 flies 23 , 26 and 25 , 26 and 26 and 27 yeast genetic approaches using these organisms have led to hundreds of aging genes and , perhaps surprisingly , strong evidence of evolutionary conservation among longevity pathways between disparate species , including mammals . 0 ###LEFT-WALL### 2 approaches 0 ###LEFT-WALL### 7 led 1 genetic 2 approaches 2 approaches 3 using 2 approaches 6 have 3 using 5 organisms 4 these 5 organisms 6 have 7 led 7 led 8 to 7 led 23 among 7 led 26 between 8 to 9 hundreds 9 hundreds 10 of 10 of 13 and 11 aging 12 genes 12 genes 13 and 13 and 19 evidence 13 and 20 of 14 , 15 perhaps 14 , 16 surprisingly 16 surprisingly 17 , 16 surprisingly 18 strong 18 strong 19 evidence 20 of 22 conservation 21 evolutionary 22 conservation 23 among 25 pathways 24 longevity 25 pathways 26 between 28 species 27 disparate 28 species 28 species 30 including 29 , 30 including 30 including 31 mammals 30 including 32 . current studies suggest that this conservation may extend to humans . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 3 suggest 0 ###LEFT-WALL### 11 . 1 current 2 studies 2 studies 3 suggest 3 suggest 4 that 4 that 6 conservation 4 that 8 extend 5 this 6 conservation 6 conservation 7 may 7 may 8 extend 8 extend 9 to 9 to 10 humans finally , small molecules such as rapamycin and resveratrol have been identified that slow aging in model organisms , although only rapamycin to date impacts longevity in mice . 0 ###LEFT-WALL### 4 molecules 0 ###LEFT-WALL### 11 been 1 finally 2 , 1 finally 4 molecules 3 small 4 molecules 4 molecules 6 as 4 molecules 10 have 5 such 6 as 6 as 8 and 7 rapamycin 8 and 8 and 9 resveratrol 10 have 11 been 11 been 15 aging 11 been 16 in 11 been 20 although 12 identified 15 aging 13 that 14 slow 14 slow 15 aging 16 in 18 organisms 17 model 18 organisms 19 , 20 although 20 although 21 only 20 although 25 impacts 20 although 29 . 21 only 22 rapamycin 22 rapamycin 24 date 22 rapamycin 25 impacts 23 to 24 date 25 impacts 26 longevity 25 impacts 27 in 27 in 28 mice the potential now exists to delay human aging , whether it is through known classes of small molecules or a plethora of emerging ones . 0 ###LEFT-WALL### 2 potential 0 ###LEFT-WALL### 4 exists 1 the 2 potential 2 potential 4 exists 3 now 4 exists 4 exists 5 to 5 to 6 delay 6 delay 8 aging 6 delay 10 whether 7 human 8 aging 9 , 10 whether 10 whether 11 it 10 whether 12 is 10 whether 25 . 11 it 12 is 12 is 13 through 13 through 19 or 14 known 15 classes 15 classes 16 of 15 classes 19 or 16 of 18 molecules 17 small 18 molecules 19 or 21 plethora 19 or 22 of 20 a 21 plethora 22 of 24 ones 23 emerging 24 ones but how can a drug that slows aging become approved and make it to market when aging is not defined as a disease . 0 ###LEFT-WALL### 1 but 0 ###LEFT-WALL### 24 . 1 but 2 how 1 but 11 and 2 how 3 can 3 can 5 drug 3 can 11 and 4 a 5 drug 5 drug 6 that 5 drug 7 slows 5 drug 8 aging 5 drug 9 become 6 that 7 slows 10 approved 11 and 11 and 12 make 12 make 13 it 12 make 15 market 12 make 16 when 14 to 15 market 16 when 17 aging 16 when 20 defined 17 aging 18 is 18 is 19 not 18 is 20 defined 20 defined 21 as 21 as 23 disease 22 a 23 disease here , we discuss the strategies to translate discoveries from aging research into drugs . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 discuss 0 ###LEFT-WALL### 15 . 1 here 2 , 1 here 3 we 3 we 4 discuss 4 discuss 6 strategies 4 discuss 7 to 5 the 6 strategies 7 to 8 translate 8 translate 9 discoveries 9 discoveries 10 from 10 from 11 aging 11 aging 12 research 11 aging 13 into 13 into 14 drugs will aging research lead to novel therapies toward chronic disease [,] prevention of disease or be targeted directly at extending lifespan ? 0 ###LEFT-WALL### 1 will 0 ###LEFT-WALL### 22 ? 1 will 2 aging 1 will 15 or 2 aging 3 research 4 lead 5 to 4 lead 8 toward 4 lead 15 or 5 to 7 therapies 6 novel 7 therapies 8 toward 12 prevention 9 chronic 10 disease 10 disease 12 prevention 12 prevention 13 of 13 of 14 disease 15 or 16 be 16 be 17 targeted 17 targeted 18 directly 17 targeted 19 at 17 targeted 21 lifespan 19 at 20 extending osteoarthritis ( oa ) is the most common chronic condition and principal cause of disability among older adults . 0 ###LEFT-WALL### 3 oa 0 ###LEFT-WALL### 5 is 0 ###LEFT-WALL### 19 . 1 osteoarthritis 3 oa 2 ( 3 oa 3 oa 4 ) 3 oa 5 is 5 is 11 and 6 the 7 most 7 most 10 condition 8 common 10 condition 9 chronic 10 condition 10 condition 11 and 11 and 13 cause 11 and 14 of 12 principal 13 cause 14 of 15 disability 15 disability 16 among 16 among 18 adults 17 older 18 adults the current obesity epidemic has contributed to this high prevalence rate . 0 ###LEFT-WALL### 4 epidemic 0 ###LEFT-WALL### 6 contributed 0 ###LEFT-WALL### 12 . 1 the 4 epidemic 2 current 3 obesity 3 obesity 4 epidemic 4 epidemic 5 has 5 has 6 contributed 6 contributed 7 to 7 to 11 rate 8 this 11 rate 9 high 10 prevalence 10 prevalence 11 rate fortunately both oa symptoms and obesity can be ameliorated through lifestyle modifications . 0 ###LEFT-WALL### 5 and 0 ###LEFT-WALL### 9 ameliorated 0 ###LEFT-WALL### 13 . 1 fortunately 5 and 2 both 4 symptoms 3 oa 4 symptoms 4 symptoms 5 and 5 and 6 obesity 5 and 7 can 7 can 8 be 8 be 9 ameliorated 9 ameliorated 10 through 10 through 12 modifications 11 lifestyle 12 modifications physical activity ( pa ) combined with weight management improves physical [function] among obese persons with knee oa but evidence - based interventions that combine pa and weight management are limited for this population . 0 ###LEFT-WALL### 2 activity 0 ###LEFT-WALL### 6 combined 0 ###LEFT-WALL### 21 - 0 ###LEFT-WALL### 35 . 1 physical 2 activity 2 activity 4 pa 2 activity 6 combined 3 ( 4 pa 4 pa 5 ) 6 combined 7 with 7 with 8 weight 7 with 11 physical 8 weight 9 management 8 weight 10 improves 9 management 10 improves 11 physical 13 among 11 physical 16 with 13 among 15 persons 14 obese 15 persons 16 with 18 oa 16 with 19 but 17 knee 18 oa 19 but 20 evidence 21 - 22 based 21 - 30 are 22 based 30 are 23 interventions 24 that 23 interventions 27 and 23 interventions 30 are 24 that 27 and 25 combine 26 pa 25 combine 27 and 27 and 28 weight 28 weight 29 management 30 are 31 limited 31 limited 32 for 32 for 34 population 33 this 34 population this paper describes a comparative effectiveness trial testing an evidence [-] based pa program for adults with lower extremity ( le ) oa , fit and strong ! [,] against an enhanced version that also addresses weight management based on the evidence - based obesity reduction black intervention trial ( orbit ) . 0 ###LEFT-WALL### 2 paper 0 ###LEFT-WALL### 3 describes 1 this 2 paper 2 paper 3 describes 3 describes 7 trial 4 a 7 trial 5 comparative 7 trial 6 effectiveness 7 trial 7 trial 8 testing 8 testing 14 program 8 testing 15 for 8 testing 17 with 9 an 14 program 10 evidence 12 based 12 based 14 program 13 pa 14 program 15 for 16 adults 17 with 19 extremity 17 with 26 and 18 lower 19 extremity 19 extremity 21 le 20 ( 21 le 21 le 22 ) 23 oa 24 , 24 , 25 fit 24 , 26 and 26 and 27 strong 26 and 28 ! 26 and 30 against 30 against 33 version 31 an 33 version 32 enhanced 33 version 33 version 34 that 33 version 39 based 34 that 38 management 34 that 39 based 35 also 38 management 36 addresses 37 weight 37 weight 38 management 38 management 39 based 39 based 40 on 40 on 42 evidence 41 the 42 evidence 42 evidence 49 trial 43 - 49 trial 44 based 49 trial 45 obesity 46 reduction 46 reduction 47 black 47 black 48 intervention 48 intervention 49 trial 49 trial 51 orbit 49 trial 53 . 50 ( 51 orbit 51 orbit 52 ) adult participants ( n=400 [ )(with le oa , age 60+ , overweight/obese , and not meeting pa requirements of ≥ 150 min per week , are randomized to one of the two programs . 0 ###LEFT-WALL### 2 participants 0 ###LEFT-WALL### 28 randomized 0 ###LEFT-WALL### 35 . 1 adult 2 participants 2 participants 4 n=400 2 participants 27 are 3 ( 4 n=400 4 n=400 6 )(with 4 n=400 26 , 6 )(with 19 requirements 6 )(with 23 min 7 le 8 oa 8 oa 11 60+ 8 oa 19 requirements 9 , 11 60+ 10 age 11 60+ 11 60+ 12 , 13 overweight/obese 15 and 14 , 15 and 15 and 16 not 15 and 17 meeting 15 and 19 requirements 18 pa 19 requirements 19 requirements 20 of 20 of 21 ≥ 22 150 23 min 23 min 24 per 24 per 25 week 27 are 28 randomized 28 randomized 29 to 29 to 30 one 30 one 31 of 31 of 34 programs 32 the 33 two 33 two 34 programs both [8] - week interventions meet 3 times per week and include 60 min of strength , flexibility , and aerobic exercise instruction followed by 30 min of education/group discussion . 0 ###LEFT-WALL### 1 both 0 ###LEFT-WALL### 3 - 3 - 5 interventions 3 - 11 and 3 - 17 , 3 - 31 . 4 week 5 interventions 5 interventions 11 and 6 meet 8 times 6 meet 11 and 7 3 8 times 8 times 9 per 9 per 10 week 11 and 12 include 12 include 14 min 13 60 14 min 14 min 15 of 15 of 16 strength 17 , 30 discussion 18 flexibility 20 and 19 , 20 and 20 and 23 instruction 20 and 24 followed 20 and 30 discussion 21 aerobic 22 exercise 22 exercise 23 instruction 24 followed 25 by 25 by 27 min 26 30 27 min 27 min 28 of 28 of 29 education/group the fit and strong ! education sessions focus on using pa to manage oa ; [whereas] fit and strong ! 0 ###LEFT-WALL### 4 strong 0 ###LEFT-WALL### 5 ! 1 the 4 strong 2 fit 3 and 3 and 4 strong 5 ! 7 sessions 5 ! 8 focus 5 ! 15 ; 5 ! 20 ! 6 education 7 sessions 7 sessions 8 focus 8 focus 9 on 9 on 10 using 10 using 11 pa 10 using 12 to 10 using 13 manage 12 to 13 manage 13 manage 14 oa 15 ; 18 and 17 fit 18 and 18 and 19 strong plus addresses pa and weight loss management strategies . 0 ###LEFT-WALL### 1 plus 0 ###LEFT-WALL### 2 addresses 0 ###LEFT-WALL### 9 . 1 plus 2 addresses 2 addresses 4 and 3 pa 4 and 4 and 8 strategies 5 weight 8 strategies 6 loss 8 strategies 7 management 8 strategies maintenance of behavior change is reinforced in both groups during months 3 - 24 through telephone calls and mailed newsletters . 0 ###LEFT-WALL### 1 maintenance 0 ###LEFT-WALL### 6 reinforced 0 ###LEFT-WALL### 21 . 1 maintenance 2 of 1 maintenance 5 is 2 of 4 change 3 behavior 4 change 5 is 6 reinforced 6 reinforced 7 in 7 in 18 and 8 both 9 groups 9 groups 10 during 9 groups 15 through 9 groups 18 and 10 during 11 months 11 months 13 - 12 3 13 - 13 - 14 24 15 through 17 calls 16 telephone 17 calls 18 and 19 mailed 18 and 20 newsletters outcomes [are] assessed at baseline , [and] 2 , 6 , 12 , 18 , and 24 months . 0 ###LEFT-WALL### 16 and 0 ###LEFT-WALL### 19 . 1 outcomes 3 assessed 1 outcomes 16 and 3 assessed 4 at 4 at 5 baseline 5 baseline 8 2 5 baseline 10 6 6 , 8 2 8 2 9 , 9 , 10 6 10 6 12 12 10 6 14 18 10 6 15 , 11 , 12 12 12 12 13 , 13 , 14 18 14 18 15 , 15 , 16 and 16 and 18 months 17 24 18 months primary outcomes are dietary change at 2 months followed by weight loss at 6 months that is maintained at 24 months . 0 ###LEFT-WALL### 2 outcomes 0 ###LEFT-WALL### 3 are 0 ###LEFT-WALL### 18 maintained 1 primary 2 outcomes 2 outcomes 3 are 3 are 4 dietary 5 change 6 at 5 change 9 followed 5 change 13 at 5 change 18 maintained 6 at 8 months 7 2 8 months 9 followed 10 by 10 by 12 loss 11 weight 12 loss 13 at 15 months 14 6 15 months 16 that 17 is 17 is 18 maintained 18 maintained 19 at 18 maintained 22 . 19 at 21 months 20 24 21 months secondary outcomes assess pa , physical performance , and anxiety/depression . 0 ###LEFT-WALL### 2 outcomes 0 ###LEFT-WALL### 3 assess 0 ###LEFT-WALL### 5 , 0 ###LEFT-WALL### 11 . 1 secondary 2 outcomes 2 outcomes 3 assess 3 assess 4 pa 5 , 9 and 6 physical 7 performance 7 performance 9 and 8 , 9 and 9 and 10 anxiety/depression background : the incidence of critical limb ischemia increases with the aging of the population . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 4 incidence 2 : 9 increases 2 : 16 . 3 the 4 incidence 4 incidence 5 of 4 incidence 9 increases 5 of 8 ischemia 6 critical 7 limb 7 limb 8 ischemia 9 increases 10 with 10 with 12 aging 11 the 12 aging 12 aging 13 of 13 of 15 population 14 the 15 population two [-] thirds of patients with critical limb ischemia present [with] trophic disorders . 0 ###LEFT-WALL### 3 thirds 0 ###LEFT-WALL### 10 present 0 ###LEFT-WALL### 14 . 1 two 3 thirds 3 thirds 4 of 3 thirds 10 present 4 of 5 patients 5 patients 6 with 6 with 9 ischemia 7 critical 8 limb 8 limb 9 ischemia 10 present 13 disorders 12 trophic 13 disorders revascularization decreases the rate of amputation . 0 ###LEFT-WALL### 1 revascularization 0 ###LEFT-WALL### 2 decreases 0 ###LEFT-WALL### 7 . 1 revascularization 2 decreases 2 decreases 4 rate 3 the 4 rate 4 rate 5 of 5 of 6 amputation infected wounds with exposure of the tendons , bones , or points of articulation cannot heal in spite of bridging and local debridement . 0 ###LEFT-WALL### 11 or 0 ###LEFT-WALL### 24 . 1 infected 2 wounds 1 infected 11 or 2 wounds 3 with 3 with 4 exposure 4 exposure 5 of 5 of 7 tendons 6 the 7 tendons 7 tendons 9 bones 8 , 9 bones 9 bones 10 , 11 or 16 heal 12 points 13 of 12 points 15 cannot 13 of 14 articulation 15 cannot 16 heal 16 heal 17 in 17 in 18 spite 18 spite 19 of 19 of 23 debridement 20 bridging 21 and 21 and 22 local 21 and 23 debridement surgery associated with a distal venous bypass or recanalization and a free flap makes it possible to cover major tissue loss and offers a hemodynamic advantage by increasing the flow of the bypass , thanks to the vascular bed added by the flap . 0 ###LEFT-WALL### 1 surgery 0 ###LEFT-WALL### 14 makes 0 ###LEFT-WALL### 44 . 1 surgery 2 associated 1 surgery 14 makes 2 associated 3 with 3 with 10 and 4 a 7 bypass 5 distal 7 bypass 6 venous 7 bypass 7 bypass 8 or 8 or 9 recanalization 8 or 10 and 10 and 13 flap 11 a 13 flap 12 free 13 flap 14 makes 15 it 14 makes 16 possible 16 possible 17 to 16 possible 22 and 17 to 22 and 18 cover 21 loss 18 cover 22 and 19 major 21 loss 20 tissue 21 loss 22 and 34 , 22 and 36 to 22 and 41 by 23 offers 26 advantage 23 offers 30 flow 23 offers 34 , 24 a 26 advantage 25 hemodynamic 26 advantage 26 advantage 27 by 27 by 28 increasing 29 the 30 flow 30 flow 31 of 31 of 33 bypass 32 the 33 bypass 34 , 35 thanks 36 to 39 bed 37 the 39 bed 38 vascular 39 bed 39 bed 40 added 41 by 43 flap 42 the 43 flap it is a complex surgery because of the multiplicity of [anastomoses] on the same arterial axis , with a risk of thrombosis and complications related to the venous autograft . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 2 is 1 it 2 is 2 is 5 surgery 2 is 6 because 3 a 5 surgery 4 complex 5 surgery 6 because 7 of 7 of 9 multiplicity 8 the 9 multiplicity 9 multiplicity 10 of 9 multiplicity 18 with 10 of 12 on 12 on 16 axis 13 the 14 same 13 the 16 axis 15 arterial 16 axis 17 , 18 with 18 with 20 risk 18 with 30 . 19 a 20 risk 20 risk 21 of 20 risk 25 related 20 risk 26 to 21 of 23 and 22 thrombosis 23 and 23 and 24 complications 26 to 29 autograft 27 the 29 autograft 28 venous 29 autograft to mitigate these disadvantages , we propose a new surgical method based on the use of a single anatomic unit , the epiploic bypass flap ( bf ) , based on the gastroepiploic artery ( gea ) as the inflow for a bypass and a free flap . 0 ###LEFT-WALL### 6 we 0 ###LEFT-WALL### 7 propose 0 ###LEFT-WALL### 48 . 1 to 2 mitigate 1 to 5 , 1 to 6 we 2 mitigate 4 disadvantages 3 these 4 disadvantages 6 we 7 propose 7 propose 11 method 8 a 9 new 8 a 11 method 9 new 11 method 10 surgical 11 method 11 method 12 based 12 based 13 on 13 on 15 use 14 the 15 use 15 use 16 of 15 use 30 based 16 of 20 unit 17 a 18 single 17 a 20 unit 18 single 20 unit 19 anatomic 20 unit 20 unit 25 flap 21 , 25 flap 22 the 25 flap 23 epiploic 24 bypass 24 bypass 25 flap 25 flap 27 bf 25 flap 29 , 26 ( 27 bf 27 bf 28 ) 30 based 31 on 30 based 38 as 31 on 34 artery 32 the 34 artery 33 gastroepiploic 34 artery 34 artery 36 gea 35 ( 36 gea 36 gea 37 ) 38 as 40 inflow 39 the 40 inflow 40 inflow 41 for 41 for 44 and 42 a 43 bypass 43 bypass 44 and 44 and 47 flap 45 a 46 free 45 a 47 flap 46 free 47 flap the objective of this work was to analyze the anatomic feasibility of an epiploic bf and to determine its limits . 0 ###LEFT-WALL### 2 objective 0 ###LEFT-WALL### 21 . 1 the 2 objective 2 objective 3 of 2 objective 6 was 3 of 5 work 4 this 5 work 6 was 7 to 6 was 16 and 7 to 16 and 8 analyze 11 feasibility 8 analyze 16 and 9 the 11 feasibility 10 anatomic 11 feasibility 11 feasibility 12 of 12 of 15 bf 13 an 14 epiploic 13 an 15 bf 14 epiploic 15 bf 16 and 17 to 16 and 18 determine 17 to 18 determine 18 determine 20 limits 19 its 20 limits methods : one hundred anatomic preparations were conducted with a measure of the internal and external diameters and the lengths of gea and its branches and [a] radiograph after injection of a radiopaque product . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 6 preparations 2 : 26 and 2 : 35 . 3 one 4 hundred 4 hundred 6 preparations 5 anatomic 6 preparations 6 preparations 26 and 7 were 8 conducted 7 were 26 and 8 conducted 9 with 9 with 18 and 10 a 11 measure 11 measure 12 of 11 measure 18 and 12 of 17 diameters 13 the 17 diameters 14 internal 15 and 15 and 16 external 15 and 17 diameters 18 and 20 lengths 19 the 20 lengths 20 lengths 21 of 21 of 23 and 22 gea 23 and 23 and 25 branches 24 its 25 branches 26 and 28 radiograph 26 and 29 after 29 after 30 injection 30 injection 31 of 31 of 34 product 32 a 34 product 33 radiopaque 34 product a first clinical application was carried out . 0 ###LEFT-WALL### 4 application 0 ###LEFT-WALL### 6 carried 0 ###LEFT-WALL### 8 . 1 a 4 application 2 first 4 application 3 clinical 4 application 4 application 5 was 5 was 6 carried 6 carried 7 out results : according to the data , our study confirms the anatomic feasibility of a bf . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 7 , 0 ###LEFT-WALL### 17 . 1 results 2 : 2 : 4 to 3 according 4 to 4 to 6 data 5 the 6 data 7 , 9 study 7 , 10 confirms 8 our 9 study 9 study 10 confirms 10 confirms 13 feasibility 11 the 13 feasibility 12 anatomic 13 feasibility 13 feasibility 14 of 14 of 16 bf 15 a 16 bf the average available length of gea is 245 mm [(] range : 210 - 280 mm ) . 0 ###LEFT-WALL### 4 length 0 ###LEFT-WALL### 7 is 0 ###LEFT-WALL### 12 : 0 ###LEFT-WALL### 18 . 1 the 4 length 2 average 4 length 3 available 4 length 4 length 5 of 4 length 7 is 5 of 6 gea 7 is 11 range 8 245 9 mm 9 mm 11 range 12 : 13 210 13 210 16 mm 14 - 16 mm 15 280 16 mm 16 mm 17 ) the average proximal diameter is 3 mm , and the distal diameter is 1.5 mm . 0 ###LEFT-WALL### 4 diameter 0 ###LEFT-WALL### 5 is 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 16 . 1 the 4 diameter 2 average 4 diameter 3 proximal 4 diameter 4 diameter 5 is 5 is 7 mm 6 3 7 mm 8 , 9 and 9 and 12 diameter 9 and 13 is 10 the 12 diameter 11 distal 12 diameter 12 diameter 13 is 13 is 15 mm 14 1.5 15 mm the most distal epiploic branch that feeds the bypass is approximately 180 mm [(] range : 161 - 195 mm [ )(of the origin of the gea . 0 ###LEFT-WALL### 5 branch 0 ###LEFT-WALL### 10 is 0 ###LEFT-WALL### 16 : 0 ###LEFT-WALL### 28 . 1 the 5 branch 2 most 3 distal 3 distal 5 branch 4 epiploic 5 branch 5 branch 6 that 5 branch 7 feeds 5 branch 10 is 6 that 7 feeds 7 feeds 9 bypass 8 the 9 bypass 10 is 15 range 11 approximately 12 180 12 180 13 mm 13 mm 15 range 16 : 20 mm 17 161 18 - 18 - 19 195 18 - 20 mm 20 mm 22 )(of 22 )(of 24 origin 23 the 24 origin 24 origin 25 of 25 of 27 gea 26 the 27 gea the anatomic unit based on the gea provides an arterial graft that is relatively long and a large flap that is both malleable and resistant to infection . 0 ###LEFT-WALL### 3 unit 0 ###LEFT-WALL### 8 provides 0 ###LEFT-WALL### 28 . 1 the 3 unit 2 anatomic 3 unit 3 unit 4 based 3 unit 8 provides 4 based 5 on 5 on 7 gea 6 the 7 gea 8 provides 11 graft 9 an 10 arterial 9 an 11 graft 10 arterial 11 graft 11 graft 12 that 11 graft 13 is 12 that 13 is 13 is 14 relatively 13 is 27 infection 15 long 16 and 16 and 19 flap 16 and 20 that 16 and 26 to 16 and 27 infection 17 a 18 large 17 a 19 flap 18 large 19 flap 20 that 21 is 21 is 22 both 22 both 24 and 23 malleable 24 and 24 and 25 resistant 25 resistant 26 to conclusions : epiploic bf is a surgical technique that allows for distal revascularization and a simultaneous cover of the limb extremity . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 4 bf 2 : 5 is 2 : 22 . 3 epiploic 4 bf 4 bf 5 is 5 is 8 technique 6 a 7 surgical 6 a 8 technique 7 surgical 8 technique 8 technique 9 that 8 technique 10 allows 9 that 10 allows 10 allows 11 for 11 for 14 and 12 distal 13 revascularization 13 revascularization 14 and 14 and 17 cover 14 and 18 of 15 a 16 simultaneous 15 a 17 cover 16 simultaneous 17 cover 18 of 21 extremity 19 the 21 extremity 20 limb 21 extremity this technique can be useful in patients requiring a distal revascularization associated with a cutaneous cover . 0 ###LEFT-WALL### 2 technique 0 ###LEFT-WALL### 4 be 0 ###LEFT-WALL### 17 . 1 this 2 technique 2 technique 3 can 3 can 4 be 4 be 5 useful 5 useful 6 in 6 in 7 patients 7 patients 8 requiring 8 requiring 11 revascularization 8 requiring 12 associated 9 a 10 distal 9 a 11 revascularization 10 distal 11 revascularization 11 revascularization 12 associated 12 associated 13 with 13 with 16 cover 14 a 15 cutaneous 14 a 16 cover 15 cutaneous 16 cover globoid cell leukodystrophy is a lysosomal storage disease characterized by the loss of galactocerebrosidase . 0 ###LEFT-WALL### 3 leukodystrophy 0 ###LEFT-WALL### 4 is 0 ###LEFT-WALL### 15 . 1 globoid 3 leukodystrophy 2 cell 3 leukodystrophy 3 leukodystrophy 4 is 4 is 8 disease 5 a 6 lysosomal 5 a 8 disease 6 lysosomal 7 storage 7 storage 8 disease 8 disease 9 characterized 9 characterized 10 by 10 by 12 loss 11 the 12 loss 12 loss 13 of 13 of 14 galactocerebrosidase galactocerebrosidase loss leads to the accumulation of psychosine and subsequent oligodendrocyte cell death , demyelination , macrophage recruitment , and astroglial activation and proliferation . 0 ###LEFT-WALL### 23 and 0 ###LEFT-WALL### 25 . 1 galactocerebrosidase 2 loss 2 loss 3 leads 3 leads 4 to 3 leads 7 of 3 leads 9 and 4 to 6 accumulation 5 the 6 accumulation 7 of 8 psychosine 9 and 13 death 9 and 14 , 10 subsequent 11 oligodendrocyte 11 oligodendrocyte 12 cell 12 cell 13 death 14 , 15 demyelination 14 , 16 , 16 , 18 recruitment 16 , 20 and 17 macrophage 18 recruitment 19 , 20 and 20 and 22 activation 20 and 23 and 21 astroglial 22 activation 23 and 24 proliferation to date , no studies have elucidated the mechanism of glial cell activation and cytokine and chemokine up - regulation and release . 0 ###LEFT-WALL### 1 to 0 ###LEFT-WALL### 2 date 0 ###LEFT-WALL### 3 , 0 ###LEFT-WALL### 23 . 1 to 2 date 3 , 5 studies 3 , 7 elucidated 4 no 5 studies 5 studies 6 have 6 have 7 elucidated 7 elucidated 9 mechanism 8 the 9 mechanism 9 mechanism 10 of 10 of 21 and 11 glial 12 cell 12 cell 13 activation 13 activation 14 and 14 and 15 cytokine 14 and 16 and 16 and 20 regulation 16 and 21 and 17 chemokine 20 regulation 18 up 19 - 18 up 20 regulation 21 and 22 release we explored a novel explanation for the development of the pathological changes in the early stages of globoid cell leukodystrophy associated with [toll] - like receptor [(] tlr ) 2 up - regulation in the hindbrain and cerebellum as a response to dying oligodendrocytes . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 explored 0 ###LEFT-WALL### 32 - 0 ###LEFT-WALL### 45 . 1 we 2 explored 2 explored 5 explanation 2 explored 6 for 3 a 5 explanation 4 novel 5 explanation 6 for 8 development 7 the 8 development 8 development 9 of 9 of 12 changes 10 the 12 changes 11 pathological 12 changes 12 changes 13 in 13 in 16 stages 14 the 16 stages 15 early 16 stages 16 stages 17 of 16 stages 30 2 16 stages 31 up 17 of 18 globoid 18 globoid 20 leukodystrophy 18 globoid 22 with 18 globoid 25 like 19 cell 20 leukodystrophy 20 leukodystrophy 21 associated 21 associated 22 with 24 - 25 like 25 like 28 tlr 25 like 29 ) 26 receptor 28 tlr 30 2 31 up 32 - 33 regulation 32 - 44 oligodendrocytes 33 regulation 34 in 33 regulation 42 to 33 regulation 44 oligodendrocytes 34 in 37 and 35 the 36 hindbrain 36 hindbrain 37 and 37 and 38 cerebellum 38 cerebellum 39 as 39 as 41 response 40 a 41 response 42 to 43 dying tlr2 up - regulation on microglia/macrophages coincided with morphological changes consistent with activation at 2 and 3 weeks of age . 0 ###LEFT-WALL### 4 regulation 0 ###LEFT-WALL### 7 coincided 0 ###LEFT-WALL### 21 . 1 tlr2 4 regulation 2 up 3 - 2 up 4 regulation 4 regulation 5 on 4 regulation 7 coincided 5 on 6 microglia/macrophages 7 coincided 8 with 7 coincided 14 at 8 with 10 changes 9 morphological 10 changes 10 changes 11 consistent 11 consistent 12 with 12 with 13 activation 14 at 18 weeks 15 2 16 and 16 and 17 3 16 and 18 weeks 18 weeks 19 of 19 of 20 age tlr2 up - regulation on activated microglia/macrophages resulted in astrocyte activation and marked up - regulation of cytokines/chemokines . 0 ###LEFT-WALL### 1 tlr2 0 ###LEFT-WALL### 18 cytokines/chemokines 0 ###LEFT-WALL### 19 . 1 tlr2 4 regulation 1 tlr2 17 of 1 tlr2 18 cytokines/chemokines 2 up 3 - 2 up 4 regulation 4 regulation 5 on 4 regulation 12 and 5 on 7 microglia/macrophages 6 activated 7 microglia/macrophages 8 resulted 9 in 8 resulted 12 and 9 in 11 activation 10 astrocyte 11 activation 12 and 13 marked 13 marked 16 regulation 14 up 15 - 14 up 16 regulation 16 regulation 17 of because oligodendrocyte cell death is an important feature of globoid cell leukodystrophy , we tested the ability of tlr2 reporter cells to respond to oligodendrocyte cell death . 0 ###LEFT-WALL### 14 we 0 ###LEFT-WALL### 15 tested 0 ###LEFT-WALL### 28 . 1 because 4 death 1 because 5 is 1 because 13 , 1 because 14 we 2 oligodendrocyte 4 death 3 cell 4 death 4 death 5 is 5 is 8 feature 6 an 7 important 6 an 8 feature 7 important 8 feature 8 feature 9 of 9 of 12 leukodystrophy 10 globoid 11 cell 11 cell 12 leukodystrophy 14 we 15 tested 15 tested 17 ability 16 the 17 ability 17 ability 18 of 17 ability 22 to 17 ability 25 oligodendrocyte 18 of 21 cells 19 tlr2 21 cells 20 reporter 21 cells 22 to 23 respond 23 respond 24 to 24 to 25 oligodendrocyte 25 oligodendrocyte 27 death 26 cell 27 death these reporter cells responded in vitro to medium conditioned [by] psychosine - treated oligodendrocytes [,] indicating the likelihood that oligodendrocytes release a tlr2 ligand during apoptosis . 0 ###LEFT-WALL### 3 cells 0 ###LEFT-WALL### 4 responded 0 ###LEFT-WALL### 27 . 1 these 3 cells 2 reporter 3 cells 3 cells 4 responded 4 responded 6 vitro 4 responded 14 oligodendrocytes 4 responded 24 ligand 5 in 6 vitro 7 to 11 psychosine 7 to 12 - 7 to 14 oligodendrocytes 8 medium 11 psychosine 9 conditioned 11 psychosine 13 treated 14 oligodendrocytes 14 oligodendrocytes 16 indicating 14 oligodendrocytes 24 ligand 16 indicating 18 likelihood 17 the 18 likelihood 18 likelihood 19 that 19 that 20 oligodendrocytes 19 that 21 release 20 oligodendrocytes 21 release 21 release 23 tlr2 22 a 23 tlr2 24 ligand 25 during 25 during 26 apoptosis tlrs are a member of the innate immune system and initiate immune and inflammatory events ; therefore , the identification of tlr2 as a potential driver in the activation of central nervous system glial activity in globoid cell leukodystrophy may provide important insight into its pathogenesis . 0 ###LEFT-WALL### 1 tlrs 0 ###LEFT-WALL### 2 are 0 ###LEFT-WALL### 16 ; 0 ###LEFT-WALL### 47 . 1 tlrs 2 are 2 are 4 member 3 a 4 member 4 member 5 of 5 of 10 and 6 the 9 system 7 innate 9 system 8 immune 9 system 9 system 10 and 10 and 15 events 11 initiate 15 events 12 immune 13 and 13 and 14 inflammatory 13 and 15 events 16 ; 20 identification 16 ; 41 provide 17 therefore 18 , 17 therefore 20 identification 19 the 20 identification 20 identification 21 of 20 identification 23 as 20 identification 27 in 20 identification 40 may 21 of 22 tlr2 23 as 26 driver 24 a 25 potential 24 a 26 driver 25 potential 26 driver 27 in 29 activation 28 the 29 activation 29 activation 30 of 30 of 35 activity 31 central 33 system 32 nervous 33 system 33 system 35 activity 34 glial 35 activity 35 activity 36 in 36 in 39 leukodystrophy 37 globoid 38 cell 38 cell 39 leukodystrophy 40 may 41 provide 41 provide 43 insight 42 important 43 insight 43 insight 44 into 44 into 46 pathogenesis 45 its 46 pathogenesis improved approaches are needed to assess bioavailability of hydrophobic organic compounds [in] contaminated [soils] . 0 ###LEFT-WALL### 2 approaches 0 ###LEFT-WALL### 4 needed 0 ###LEFT-WALL### 15 . 1 improved 2 approaches 2 approaches 3 are 3 are 4 needed 4 needed 5 to 5 to 6 assess 6 assess 7 bioavailability 7 bioavailability 8 of 8 of 11 compounds 9 hydrophobic 11 compounds 10 organic 11 compounds 11 compounds 13 contaminated performance of thin - film solid - phase extraction ( tf - spe ) using vials coated with ethylene vinyl [acetate] [was] compared to [earthworm] bioassay ( lumbricus terrestris ) . 0 ###LEFT-WALL### 1 performance 0 ###LEFT-WALL### 17 coated 0 ###LEFT-WALL### 31 . 1 performance 2 of 1 performance 15 using 1 performance 17 coated 2 of 9 extraction 3 thin 4 - 3 thin 5 film 5 film 9 extraction 6 solid 7 - 6 solid 8 phase 8 phase 9 extraction 9 extraction 11 tf 10 ( 11 tf 11 tf 13 spe 11 tf 14 ) 12 - 13 spe 13 spe 14 ) 15 using 16 vials 17 coated 18 with 17 coated 20 vinyl 18 with 19 ethylene 20 vinyl 23 compared 20 vinyl 24 to 20 vinyl 26 bioassay 20 vinyl 29 terrestris 24 to 26 bioassay 27 ( 29 terrestris 28 lumbricus 29 terrestris 29 terrestris 30 ) a ddt and dieldrin contaminated soil was amended with four organic carbon materials to assess the change in bioavailability . 0 ###LEFT-WALL### 2 ddt 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 20 . 1 a 2 ddt 3 and 6 soil 3 and 15 assess 4 dieldrin 5 contaminated 5 contaminated 6 soil 6 soil 7 was 7 was 8 amended 8 amended 9 with 8 amended 14 to 9 with 13 materials 10 four 13 materials 11 organic 13 materials 12 carbon 13 materials 14 to 15 assess 15 assess 17 change 16 the 17 change 17 change 18 in 18 in 19 bioavailability addition of organic carbon significantly lowered bioavailability for all compounds except for 4,4 ['] - ddt . 0 ###LEFT-WALL### 1 addition 0 ###LEFT-WALL### 6 lowered 0 ###LEFT-WALL### 15 - 1 addition 2 of 1 addition 6 lowered 2 of 4 carbon 3 organic 4 carbon 5 significantly 6 lowered 6 lowered 7 bioavailability 6 lowered 11 except 7 bioavailability 8 for 8 for 10 compounds 9 all 10 compounds 11 except 12 for 12 for 13 4,4 15 - 16 ddt 15 - 17 . equilibrium concentrations of compounds in the polymer were correlated with uptake by earthworms after 48 d exposure [(] r ( 2 ) = 0.97 [;] p < 0.001 ) , indicating tf - spe provided an accurate uptake simulation . 0 ###LEFT-WALL### 2 concentrations 0 ###LEFT-WALL### 9 correlated 1 equilibrium 2 concentrations 2 concentrations 3 of 2 concentrations 8 were 3 of 4 compounds 4 compounds 5 in 5 in 7 polymer 6 the 7 polymer 8 were 9 correlated 9 correlated 10 with 10 with 11 uptake 11 uptake 12 by 12 by 13 earthworms 13 earthworms 14 after 13 earthworms 17 exposure 13 earthworms 23 = 14 after 16 d 15 48 16 d 17 exposure 19 r 17 exposure 21 2 17 exposure 23 = 20 ( 21 2 21 2 22 ) 23 = 27 < 23 = 31 indicating 24 0.97 27 < 26 p 27 < 27 < 28 0.001 27 < 29 ) 30 , 31 indicating 31 indicating 34 spe 31 indicating 35 provided 31 indicating 40 . 32 tf 34 spe 33 - 34 spe 34 spe 35 provided 35 provided 39 simulation 36 an 39 simulation 37 accurate 38 uptake 38 uptake 39 simulation bioavailability of residues in soil was compared with a spiked soil aged [for] 90 d [in] laboratory . 0 ###LEFT-WALL### 1 bioavailability 0 ###LEFT-WALL### 7 compared 0 ###LEFT-WALL### 18 . 1 bioavailability 2 of 1 bioavailability 6 was 2 of 3 residues 3 residues 4 in 4 in 5 soil 6 was 7 compared 7 compared 8 with 8 with 17 laboratory 9 a 17 laboratory 10 spiked 11 soil 11 soil 12 aged 12 aged 17 laboratory 14 90 15 d 15 d 17 laboratory dieldrin and ddx were respectively 18 % and 11 [%] less bioavailable in contaminated soil relative to spiked soil despite >40 [yr] of aging . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 4 were 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 25 . 1 dieldrin 2 and 2 and 3 ddx 2 and 4 were 4 were 5 respectively 4 were 7 % 6 18 7 % 8 and 13 in 8 and 14 contaminated 9 11 13 in 11 less 12 bioavailable 12 bioavailable 13 in 13 in 14 contaminated 14 contaminated 15 soil 15 soil 16 relative 16 relative 17 to 16 relative 20 despite 17 to 19 soil 18 spiked 19 soil 20 despite 21 >40 21 >40 23 of 23 of 24 aging results show that tf - spe can be useful in examining potential risks associated with contaminated soils and to test effectiveness of remediation efforts . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 show 0 ###LEFT-WALL### 25 . 1 results 2 show 2 show 3 that 3 that 6 spe 3 that 18 and 4 tf 6 spe 5 - 6 spe 6 spe 7 can 7 can 18 and 8 be 9 useful 8 be 18 and 9 useful 10 in 10 in 11 examining 11 examining 12 potential 11 examining 17 soils 12 potential 13 risks 12 potential 15 with 12 potential 16 contaminated 12 potential 17 soils 13 risks 14 associated 14 associated 15 with 18 and 19 to 18 and 20 test 19 to 20 test 20 test 21 effectiveness 21 effectiveness 22 of 22 of 24 efforts 23 remediation 24 efforts alterations in cerebrovascular structure and function may underlie the most common age - associated cognitive , psychiatric , and neurological conditions presented by older adults . 0 ###LEFT-WALL### 5 and 0 ###LEFT-WALL### 8 underlie 0 ###LEFT-WALL### 13 - 0 ###LEFT-WALL### 26 . 1 alterations 2 in 1 alterations 5 and 2 in 4 structure 3 cerebrovascular 4 structure 5 and 6 function 5 and 7 may 7 may 8 underlie 8 underlie 12 age 9 the 10 most 10 most 12 age 11 common 12 age 13 - 21 conditions 14 associated 21 conditions 15 cognitive 16 , 16 , 17 psychiatric 16 , 19 and 18 , 19 and 19 and 20 neurological 19 and 21 conditions 21 conditions 22 presented 22 presented 23 by 23 by 25 adults 24 older 25 adults although much remains to understand , existing research suggests several age - associated detrimental conditions may be mediated through sometimes subtle small vessel [-] induced damage to the cerebral white matter . 0 ###LEFT-WALL### 15 conditions 0 ###LEFT-WALL### 17 be 0 ###LEFT-WALL### 32 . 1 although 2 much 1 although 3 remains 1 although 15 conditions 2 much 3 remains 4 to 6 , 4 to 12 - 4 to 15 conditions 5 understand 6 , 6 , 11 age 7 existing 8 research 8 research 9 suggests 9 suggests 10 several 9 suggests 11 age 13 associated 15 conditions 14 detrimental 15 conditions 15 conditions 16 may 16 may 17 be 17 be 26 damage 18 mediated 23 vessel 19 through 23 vessel 20 sometimes 21 subtle 21 subtle 23 vessel 22 small 23 vessel 23 vessel 25 induced 25 induced 26 damage 26 damage 27 to 27 to 31 matter 28 the 31 matter 29 cerebral 31 matter 30 white 31 matter here we review a selected portion of the vast work that demonstrates links between changes in vascular and neural health as a function of advancing age , and how even changes in low - to [-] moderate risk individuals , potentially beginning early in the adult age - span , [may] [have] an important impact on functional status in late life . 0 ###LEFT-WALL### 2 we 0 ###LEFT-WALL### 3 review 1 here 2 we 2 we 3 review 3 review 6 portion 4 a 6 portion 5 selected 6 portion 6 portion 7 of 6 portion 11 that 6 portion 12 demonstrates 6 portion 14 between 7 of 10 work 8 the 10 work 9 vast 10 work 11 that 12 demonstrates 12 demonstrates 13 links 14 between 15 changes 15 changes 16 in 15 changes 21 as 16 in 20 health 17 vascular 18 and 18 and 19 neural 18 and 20 health 21 as 31 changes 22 a 23 function 23 function 24 of 23 function 28 and 24 of 26 age 25 advancing 26 age 27 , 28 and 28 and 29 how 28 and 31 changes 30 even 31 changes 31 changes 32 in 31 changes 42 beginning 32 in 33 low 33 low 35 to 34 - 35 to 35 to 37 moderate 35 to 40 , 37 moderate 39 individuals 38 risk 39 individuals 41 potentially 42 beginning 42 beginning 43 early 42 beginning 44 in 44 in 47 age 45 the 47 age 46 adult 47 age 47 age 49 span 47 age 55 impact 48 - 49 span 49 span 50 , 50 , 55 impact 53 an 54 important 53 an 55 impact 54 important 55 impact 55 impact 56 on 55 impact 62 . 56 on 58 status 57 functional 58 status 58 status 59 in 59 in 61 life 60 late 61 life objective : to reflect on the challenges of caring for an elderly ill parent who lives [afar] and to pronounce the importance of system [-] wide standards in nursing homes and elderly care . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 34 . 1 objective 2 : 2 : 3 to 2 : 18 and 3 to 18 and 4 reflect 5 on 4 reflect 18 and 5 on 7 challenges 6 the 7 challenges 7 challenges 8 of 8 of 9 caring 9 caring 10 for 10 for 14 parent 11 an 12 elderly 11 an 14 parent 12 elderly 14 parent 13 ill 14 parent 14 parent 15 who 14 parent 16 lives 15 who 16 lives 18 and 19 to 18 and 20 pronounce 19 to 20 pronounce 20 pronounce 22 importance 20 pronounce 28 in 21 the 22 importance 22 importance 23 of 23 of 27 standards 24 system 27 standards 26 wide 27 standards 28 in 29 nursing 29 nursing 31 and 30 homes 31 and 31 and 33 care 32 elderly 33 care method : personal memoire in which the author conjures up powerful images of contrasting healthcare systems and the tension of living in two countries . 0 ###LEFT-WALL### 1 method 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 25 . 2 : 17 and 3 personal 4 memoire 4 memoire 5 in 4 memoire 17 and 5 in 6 which 5 in 8 author 5 in 9 conjures 7 the 8 author 8 author 9 conjures 9 conjures 12 images 10 up 12 images 11 powerful 12 images 12 images 13 of 13 of 14 contrasting 14 contrasting 16 systems 15 healthcare 16 systems 17 and 19 tension 18 the 19 tension 19 tension 20 of 20 of 21 living 21 living 22 in 22 in 24 countries 23 two 24 countries results : the author discusses many aspects of [healthcare] for the elderly . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 4 author 2 : 5 discusses 2 : 13 . 3 the 4 author 4 author 5 discusses 5 discusses 7 aspects 6 many 7 aspects 7 aspects 8 of 8 of 10 for 10 for 12 elderly 11 the 12 elderly some of the pictures depicted include the picture of a gradually declining memory of an alzheimer 's disease patient and the challenges of elderly care . 0 ###LEFT-WALL### 4 pictures 0 ###LEFT-WALL### 6 include 0 ###LEFT-WALL### 26 . 1 some 2 of 1 some 4 pictures 2 of 4 pictures 3 the 4 pictures 4 pictures 5 depicted 4 pictures 6 include 6 include 8 picture 7 the 8 picture 8 picture 9 of 9 of 13 memory 10 a 13 memory 11 gradually 12 declining 12 declining 13 memory 13 memory 14 of 13 memory 23 of 14 of 20 and 15 an 16 alzheimer 16 alzheimer 17 's 17 's 19 patient 18 disease 19 patient 19 patient 20 and 20 and 22 challenges 21 the 22 challenges 23 of 25 care 24 elderly 25 care conclusion : there is a value of medical knowledge , an importance of nursing homes designs and regulation , and a significance of simple concepts such as a " do - not - resuscitate " order . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 37 . 2 : 3 there 2 : 4 is 2 : 31 - 3 there 4 is 4 is 6 value 5 a 6 value 6 value 7 of 7 of 20 and 8 medical 9 knowledge 9 knowledge 10 , 10 , 12 importance 10 , 17 and 11 an 12 importance 12 importance 13 of 13 of 14 nursing 14 nursing 16 designs 15 homes 16 designs 17 and 18 regulation 17 and 20 and 19 , 20 and 20 and 22 significance 20 and 23 of 20 and 27 as 21 a 22 significance 23 of 25 concepts 24 simple 25 concepts 26 such 27 as 27 as 30 do 28 a 29 " 28 a 30 do 31 - 32 not 31 - 33 - 33 - 34 resuscitate 34 resuscitate 35 " 34 resuscitate 36 order practice implications : care for the elderly can be exhausting physically and emotionally ; system - wide changes and standards are important in minimizing its impact . 0 ###LEFT-WALL### 2 implications 0 ###LEFT-WALL### 3 : 1 practice 2 implications 3 : 4 care 3 : 9 be 3 : 14 ; 4 care 5 for 4 care 9 be 5 for 8 can 6 the 8 can 7 elderly 8 can 9 be 10 exhausting 9 be 12 and 11 physically 12 and 12 and 13 emotionally 14 ; 15 system 14 ; 16 - 16 - 19 and 16 - 21 are 16 - 27 . 17 wide 18 changes 18 changes 19 and 19 and 20 standards 19 and 21 are 21 are 22 important 22 important 23 in 23 in 24 minimizing 24 minimizing 26 impact 25 its 26 impact changes in cytoprotective signaling may influence cardiac aging , and underpin sensitization to ischemic insult and desensitization to ['] anti - ischemic ['] therapies . 0 ###LEFT-WALL### 1 changes 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 25 . 1 changes 2 in 1 changes 10 and 2 in 4 signaling 3 cytoprotective 4 signaling 5 may 6 influence 5 may 10 and 6 influence 8 aging 7 cardiac 8 aging 9 , 10 and 10 and 11 underpin 11 underpin 12 sensitization 11 underpin 13 to 11 underpin 18 to 13 to 16 and 14 ischemic 15 insult 15 insult 16 and 16 and 17 desensitization 18 to 24 therapies 20 anti 21 - 20 anti 24 therapies 22 ischemic 24 therapies we tested whether age [-] dependent shifts in ischemia - reperfusion ( i - r ) tolerance in murine and human myocardium are associated with reduced efficacies and coupling of membrane , cytoplasmic and mitochondrial survival - signaling . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 tested 0 ###LEFT-WALL### 32 , 1 we 2 tested 2 tested 3 whether 2 tested 25 with 3 whether 20 and 3 whether 24 associated 4 age 7 shifts 6 dependent 7 shifts 7 shifts 8 in 7 shifts 20 and 8 in 17 tolerance 9 ischemia 10 - 9 ischemia 11 reperfusion 11 reperfusion 17 tolerance 12 ( 14 - 13 i 14 - 14 - 15 r 14 - 16 ) 14 - 17 tolerance 17 tolerance 18 in 18 in 19 murine 20 and 22 myocardium 20 and 23 are 21 human 22 myocardium 23 are 24 associated 25 with 28 and 26 reduced 27 efficacies 27 efficacies 28 and 28 and 29 coupling 28 and 30 of 30 of 31 membrane 32 , 34 and 33 cytoplasmic 34 and 34 and 36 survival 34 and 38 signaling 35 mitochondrial 36 survival 37 - 38 signaling 38 signaling 39 . hormesis ( exemplified in ischemic preconditioning [;] ipc ) and expression of proteins influencing signaling/stress - resistance were also assessed in mice . 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 20 assessed 0 ###LEFT-WALL### 23 . 1 hormesis 3 exemplified 1 hormesis 10 and 2 ( 3 exemplified 3 exemplified 4 in 3 exemplified 9 ) 4 in 8 ipc 5 ischemic 8 ipc 6 preconditioning 8 ipc 10 and 11 expression 10 and 12 of 10 and 18 were 12 of 13 proteins 13 proteins 14 influencing 14 influencing 17 resistance 15 signaling/stress 16 - 15 signaling/stress 17 resistance 18 were 19 also 18 were 20 assessed 20 assessed 21 in 21 in 22 mice mouse hearts [(] 18 vs [.] 2 - 4 mo ) and human atrial tissue ( 75±2 vs [.] 55±2 [yrs] ) exhibited profound age - dependent reductions in i - r tolerance . 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 23 exhibited 0 ###LEFT-WALL### 26 - 0 ###LEFT-WALL### 34 . 1 mouse 2 hearts 2 hearts 4 18 2 hearts 5 vs 2 hearts 12 and 5 vs 7 2 7 2 10 mo 8 - 10 mo 9 4 10 mo 10 mo 11 ) 12 and 15 tissue 12 and 17 75±2 12 and 23 exhibited 13 human 15 tissue 14 atrial 15 tissue 16 ( 17 75±2 17 75±2 18 vs 17 75±2 22 ) 18 vs 20 55±2 23 exhibited 25 age 24 profound 25 age 26 - 28 reductions 27 dependent 28 reductions 28 reductions 29 in 29 in 33 tolerance 30 i 31 - 31 - 32 r 31 - 33 tolerance in mice aging negated cardioprotection via ipc , g - protein coupled [receptor] ( gpcr ) agonism ( opioid , a1 and a3 adenosine receptors ) and distal protein kinase [c] ( pkc ) activation ( 4 nm phorbol 12 - myristate 13 - acetate ; pma [ )( 0 ###LEFT-WALL### 3 aging 0 ###LEFT-WALL### 4 negated 0 ###LEFT-WALL### 44 - 1 in 2 mice 1 in 3 aging 3 aging 4 negated 4 negated 35 activation 5 cardioprotection 6 via 5 cardioprotection 27 and 6 via 17 agonism 7 ipc 10 - 7 ipc 17 agonism 8 , 10 - 9 g 10 - 10 - 11 protein 10 - 16 ) 11 protein 12 coupled 11 protein 15 gpcr 14 ( 15 gpcr 15 gpcr 16 ) 17 agonism 22 and 18 ( 22 and 19 opioid 20 , 20 , 21 a1 20 , 22 and 22 and 25 receptors 22 and 26 ) 23 a3 24 adenosine 24 adenosine 25 receptors 27 and 30 kinase 27 and 33 pkc 27 and 35 activation 28 distal 30 kinase 29 protein 30 kinase 32 ( 33 pkc 33 pkc 34 ) 35 activation 39 phorbol 36 ( 39 phorbol 37 4 38 nm 38 nm 39 phorbol 39 phorbol 40 12 39 phorbol 42 myristate 39 phorbol 44 - 41 - 42 myristate 42 myristate 43 13 42 myristate 44 - 44 - 45 acetate 44 - 46 ; 44 - 49 )( 46 ; 47 pma a similar pattern of change in protective efficacies was observed in human tissue . 0 ###LEFT-WALL### 3 pattern 0 ###LEFT-WALL### 10 observed 0 ###LEFT-WALL### 14 . 1 a 2 similar 1 a 3 pattern 2 similar 3 pattern 3 pattern 4 of 3 pattern 9 was 4 of 5 change 5 change 6 in 6 in 8 efficacies 7 protective 8 efficacies 9 was 10 observed 10 observed 11 in 11 in 13 tissue 12 human 13 tissue murine hearts exhibited molecular changes consistent with altered membrane control ( reduced caveolin - 3 , cholesterol and caveolae ) , kinase signaling ( reduced p70 ribosomal s6 kinase [;] p70s6 [k] [ )(and stress - resistance ( increased [g] - protein receptor kinase 2 , grk2 [;] glycogen synthase kinase 3β , gsk3β [;] and cytosolic cytochrome [c] ) . 1 murine 3 exhibited 2 hearts 3 exhibited 3 exhibited 5 changes 4 molecular 5 changes 5 changes 6 consistent 5 changes 10 control 6 consistent 7 with 7 with 9 membrane 8 altered 9 membrane 10 control 14 - 10 control 22 kinase 11 ( 14 - 12 reduced 13 caveolin 13 caveolin 14 - 14 - 15 3 14 - 21 , 15 3 18 and 16 , 18 and 17 cholesterol 18 and 18 and 19 caveolae 18 and 20 ) 18 and 21 , 22 kinase 23 signaling 23 signaling 25 reduced 23 signaling 34 )(and 24 ( 25 reduced 26 p70 31 p70s6 27 ribosomal 28 s6 28 s6 29 kinase 29 kinase 31 p70s6 31 p70s6 34 )(and 34 )(and 35 stress 34 )(and 36 - 34 )(and 41 - 36 - 41 - 37 resistance 39 increased 37 resistance 41 - 38 ( 39 increased 41 - 44 kinase 42 protein 44 kinase 43 receptor 44 kinase 44 kinase 45 2 44 kinase 56 and 46 , 56 and 47 grk2 52 3β 49 glycogen 52 3β 50 synthase 52 3β 51 kinase 52 3β 52 3β 53 , 53 , 54 gsk3β 53 , 56 and 56 and 58 cytochrome 56 and 60 ) 56 and 61 . 57 cytosolic 58 cytochrome in summary , myocardial i - r tolerance declines with age in association with dysfunctional hormesis and transduction of survival signals from gpcrs/pkc to mitochondrial effectors . 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 27 . 1 in 9 declines 2 summary 3 , 2 summary 8 tolerance 4 myocardial 8 tolerance 5 i 6 - 6 - 7 r 6 - 8 tolerance 8 tolerance 9 declines 9 declines 10 with 9 declines 17 and 10 with 11 age 11 age 13 association 11 age 14 with 12 in 13 association 14 with 16 hormesis 15 dysfunctional 16 hormesis 17 and 18 transduction 17 and 19 of 17 and 22 from 19 of 21 signals 20 survival 21 signals 22 from 23 gpcrs/pkc 23 gpcrs/pkc 24 to 24 to 26 effectors 25 mitochondrial 26 effectors differential changes in proteins governing caveolar and mitochondrial function may contribute to signal dysfunction and stress - intolerance . 0 ###LEFT-WALL### 1 differential 0 ###LEFT-WALL### 2 changes 0 ###LEFT-WALL### 17 - 0 ###LEFT-WALL### 19 . 1 differential 2 changes 2 changes 3 in 2 changes 12 to 3 in 4 proteins 4 proteins 5 governing 4 proteins 7 and 4 proteins 11 contribute 6 caveolar 7 and 7 and 9 function 7 and 10 may 8 mitochondrial 9 function 10 may 11 contribute 12 to 15 and 13 signal 14 dysfunction 14 dysfunction 15 and 15 and 16 stress 17 - 18 intolerance objective : to obtain specific bioelectrical impedance vector reference values for the healthy elderly italian population , and to study age - and sex - related differences in body composition . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 2 : 3 to 2 : 4 obtain 2 : 26 related 2 : 31 . 3 to 4 obtain 4 obtain 10 values 4 obtain 18 and 5 specific 8 vector 6 bioelectrical 8 vector 7 impedance 8 vector 8 vector 10 values 9 reference 10 values 11 for 16 population 11 for 18 and 12 the 16 population 13 healthy 15 italian 14 elderly 15 italian 15 italian 16 population 17 , 18 and 18 and 19 to 19 to 23 and 20 study 21 age 21 age 23 and 22 - 23 and 23 and 24 sex 25 - 26 related 26 related 27 differences 26 related 28 in 28 in 30 composition 29 body 30 composition design : the study group consisted of 560 healthy individuals ( 265 men and 295 women ) aged 65 to 100 [y] , whose anthropometric ( height , weight , and calf , arm and waist circumferences ) and bioelectrical measurements ( resistance [ r ] and reactance [ xc ] , at 50 khz and 800 μa ) were recorded . 0 ###LEFT-WALL### 1 design 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 62 . 2 : 5 group 2 : 6 consisted 2 : 23 , 3 the 5 group 4 study 5 group 5 group 6 consisted 6 consisted 7 of 7 of 10 individuals 8 560 10 individuals 9 healthy 10 individuals 10 individuals 14 and 11 ( 14 and 12 265 13 men 13 men 14 and 14 and 16 women 14 and 17 ) 14 and 18 aged 14 and 23 , 15 295 16 women 18 aged 20 to 19 65 20 to 20 to 21 100 23 , 24 whose 23 , 61 recorded 24 whose 29 weight 25 anthropometric 27 height 25 anthropometric 29 weight 26 ( 27 height 27 height 28 , 29 weight 31 and 30 , 31 and 31 and 32 calf 31 and 33 , 33 , 34 arm 33 , 35 and 35 and 37 circumferences 35 and 38 ) 35 and 39 and 36 waist 37 circumferences 39 and 41 measurements 39 and 43 resistance 39 and 47 and 40 bioelectrical 41 measurements 42 ( 43 resistance 43 resistance 45 r 43 resistance 46 ] 44 [ 45 r 45 r 46 ] 47 and 48 reactance 47 and 50 xc 47 and 53 at 47 and 60 were 49 [ 50 xc 50 xc 51 ] 52 , 53 at 53 at 56 and 53 at 59 ) 54 50 55 khz 55 khz 56 and 56 and 58 μa 57 800 58 μa 60 were 61 recorded r ( [ω] [ )(and xc [(] [ω] ) values were standardized for stature ( [h] , [m] [ )(to obtain the classic bioelectrical values . 0 ###LEFT-WALL### 5 )(and 0 ###LEFT-WALL### 26 . 1 r 5 )(and 2 ( 5 )(and 5 )(and 6 xc 5 )(and 9 ) 5 )(and 10 values 5 )(and 21 obtain 10 values 17 , 11 were 12 standardized 11 were 17 , 12 standardized 13 for 13 for 14 stature 15 ( 17 , 17 , 21 obtain 20 )(to 21 obtain 21 obtain 25 values 22 the 25 values 23 classic 25 values 24 bioelectrical 25 values specific [values] ( resistivity [ rsp ] and reactivity [ xcsp ] , ω·cm ) were obtained by multiplying r and xc by a correction factor ( [a/l] [ )(that includes an estimate of the cross - sectional area of the body ( a=0.45 arm area+0.10 waist area+0.45 calf area ) , [where] l=1.1h . 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 17 obtained 1 specific 4 resistivity 1 specific 8 and 3 ( 4 resistivity 4 resistivity 6 rsp 4 resistivity 7 ] 5 [ 6 rsp 6 rsp 7 ] 8 and 9 reactivity 8 and 11 xcsp 8 and 14 ω·cm 8 and 16 were 10 [ 11 xcsp 11 xcsp 12 ] 13 , 14 ω·cm 14 ω·cm 15 ) 16 were 17 obtained 17 obtained 18 by 17 obtained 23 by 18 by 19 multiplying 19 multiplying 21 and 20 r 21 and 21 and 22 xc 23 by 26 factor 24 a 25 correction 24 a 26 factor 25 correction 26 factor 26 factor 30 )(that 26 factor 31 includes 27 ( 30 )(that 30 )(that 31 includes 31 includes 33 estimate 32 an 33 estimate 33 estimate 34 of 34 of 36 cross 35 the 36 cross 36 cross 39 area 37 - 39 area 38 sectional 39 area 39 area 40 of 39 area 54 l=1.1h 39 area 55 . 40 of 42 body 41 the 42 body 42 body 50 area 43 ( 50 area 44 a=0.45 48 area+0.45 45 arm 47 waist 46 area+0.10 47 waist 47 waist 48 area+0.45 48 area+0.45 50 area 49 calf 50 area 50 area 51 ) 52 , 54 l=1.1h 54 l=1.1h 55 . results : descriptive statistics were : rsp ( 391.8±57.9 ) , xcsp ( 42.6±9.9 ) , zsp ( 394.2±58.2 ) , phase angle [(] 6.2°±1.2 ) in men [;] rsp ( 462.0±80.1 ) , xcsp ( 47.9±11.2 ) , zsp ( 464.6±80.5 ) , phase angle [(] 5.9°±1.0 ) in women . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 3 descriptive 2 : 6 : 2 : 52 . 3 descriptive 4 statistics 3 descriptive 5 were 3 descriptive 6 : 4 statistics 5 were 6 : 7 rsp 6 : 27 in 6 : 50 in 7 rsp 9 391.8±57.9 7 rsp 12 xcsp 7 rsp 17 zsp 8 ( 9 391.8±57.9 9 391.8±57.9 10 ) 11 , 12 xcsp 12 xcsp 14 42.6±9.9 12 xcsp 16 , 13 ( 14 42.6±9.9 14 42.6±9.9 15 ) 16 , 17 zsp 17 zsp 19 394.2±58.2 17 zsp 25 6.2°±1.2 17 zsp 26 ) 18 ( 19 394.2±58.2 19 394.2±58.2 20 ) 21 , 25 6.2°±1.2 22 phase 23 angle 23 angle 25 6.2°±1.2 25 6.2°±1.2 26 ) 27 in 30 rsp 28 men 30 rsp 30 rsp 32 462.0±80.1 30 rsp 35 xcsp 30 rsp 40 zsp 31 ( 32 462.0±80.1 32 462.0±80.1 33 ) 34 , 35 xcsp 35 xcsp 37 47.9±11.2 35 xcsp 38 ) 36 ( 37 47.9±11.2 37 47.9±11.2 38 ) 39 , 40 zsp 40 zsp 42 464.6±80.5 40 zsp 48 5.9°±1.0 40 zsp 49 ) 41 ( 42 464.6±80.5 42 464.6±80.5 43 ) 44 , 48 5.9°±1.0 45 phase 46 angle 46 angle 48 5.9°±1.0 48 5.9°±1.0 49 ) 50 in 51 women the xcsp and phase angle values showed a significant age - related decrease in both sexes , but especially in men , possibly relating to a gradual loss of muscle mass . 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 31 mass 0 ###LEFT-WALL### 32 . 1 the 2 xcsp 2 xcsp 3 and 3 and 4 phase 3 and 6 values 3 and 7 showed 3 and 31 mass 5 angle 6 values 6 values 7 showed 7 showed 10 age 8 a 9 significant 8 a 10 age 9 significant 10 age 10 age 24 relating 11 - 12 related 12 related 13 decrease 12 related 22 , 12 related 24 relating 13 decrease 18 but 14 in 16 sexes 14 in 18 but 15 both 16 sexes 17 , 18 but 18 but 19 especially 18 but 20 in 20 in 21 men 23 possibly 24 relating 24 relating 25 to 25 to 28 loss 26 a 27 gradual 26 a 28 loss 27 gradual 28 loss 28 loss 29 of 29 of 30 muscle women 's rsp and zsp values tended to drop , attributable to their declining proportion of fat mass . 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 18 mass 0 ###LEFT-WALL### 19 . 1 women 2 's 2 's 3 rsp 3 rsp 4 and 4 and 6 values 4 and 10 , 4 and 11 attributable 4 and 18 mass 5 zsp 6 values 6 values 7 tended 7 tended 8 to 8 to 9 drop 11 attributable 12 to 12 to 15 proportion 13 their 15 proportion 14 declining 15 proportion 15 proportion 16 of 16 of 17 fat a declining sexual dimorphism was also apparent . 0 ###LEFT-WALL### 4 dimorphism 0 ###LEFT-WALL### 5 was 0 ###LEFT-WALL### 8 . 1 a 4 dimorphism 2 declining 4 dimorphism 3 sexual 4 dimorphism 4 dimorphism 5 was 5 was 6 also 5 was 7 apparent conclusions : specific tolerance ellipses can be used for reference purposes for the italian population when assessing body composition in gerontological practice and for epidemiological purposes . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 5 ellipses 2 : 8 used 2 : 27 . 3 specific 4 tolerance 4 tolerance 5 ellipses 5 ellipses 6 can 6 can 7 be 7 be 8 used 8 used 9 for 8 used 16 when 9 for 11 purposes 10 reference 11 purposes 11 purposes 12 for 12 for 15 population 13 the 15 population 14 italian 15 population 16 when 17 assessing 17 assessing 19 composition 17 assessing 23 and 18 body 19 composition 20 in 22 practice 20 in 23 and 21 gerontological 22 practice 23 and 24 for 24 for 26 purposes 25 epidemiological 26 purposes treatment strategies for patients with depression and cognitive impairment ( dep - ci ) , who are at high risk to develop a clinical diagnosis of dementia , are not established . 0 ###LEFT-WALL### 2 strategies 0 ###LEFT-WALL### 31 established 0 ###LEFT-WALL### 32 . 1 treatment 2 strategies 2 strategies 3 for 2 strategies 16 who 2 strategies 29 are 3 for 7 and 4 patients 5 with 4 patients 7 and 5 with 6 depression 7 and 9 impairment 7 and 11 dep 8 cognitive 9 impairment 10 ( 11 dep 11 dep 13 ci 11 dep 14 ) 12 - 13 ci 13 ci 14 ) 15 , 16 who 16 who 17 are 16 who 28 , 17 are 18 at 17 are 27 dementia 18 at 20 risk 19 high 20 risk 20 risk 21 to 20 risk 26 of 21 to 22 develop 22 develop 25 diagnosis 23 a 24 clinical 23 a 25 diagnosis 24 clinical 25 diagnosis 25 diagnosis 26 of 29 are 30 not 29 are 31 established this issue is addressed in the donepezil treatment of cognitive impairment and depression ( dotcode ) pilot clinical trial . 0 ###LEFT-WALL### 2 issue 0 ###LEFT-WALL### 4 addressed 0 ###LEFT-WALL### 20 . 1 this 2 issue 2 issue 3 is 3 is 4 addressed 4 addressed 5 in 5 in 19 trial 6 the 19 trial 7 donepezil 19 trial 8 treatment 9 of 8 treatment 12 and 9 of 11 impairment 10 cognitive 11 impairment 12 and 13 depression 12 and 15 dotcode 12 and 19 trial 14 ( 15 dotcode 15 dotcode 16 ) 17 pilot 19 trial 18 clinical 19 trial in phase 1 , dep - ci patients receive optimized antidepressant treatment for 16 weeks . 0 ###LEFT-WALL### 8 patients 0 ###LEFT-WALL### 9 receive 0 ###LEFT-WALL### 16 . 1 in 7 ci 1 in 8 patients 2 phase 3 1 2 phase 5 dep 4 , 5 dep 5 dep 6 - 5 dep 7 ci 8 patients 9 receive 9 receive 12 treatment 10 optimized 12 treatment 11 antidepressant 12 treatment 12 treatment 13 for 13 for 15 weeks 14 16 15 weeks in phase 2 , antidepressant treatment is continued with the addition of randomized [,] double - blind treatment with donepezil or placebo . 0 ###LEFT-WALL### 6 treatment 0 ###LEFT-WALL### 8 continued 0 ###LEFT-WALL### 23 . 1 in 2 phase 1 in 4 , 1 in 6 treatment 2 phase 3 2 5 antidepressant 6 treatment 6 treatment 7 is 7 is 8 continued 8 continued 9 with 8 continued 19 with 9 with 11 addition 10 the 11 addition 11 addition 12 of 12 of 18 treatment 13 randomized 18 treatment 15 double 16 - 15 double 18 treatment 17 blind 18 treatment 19 with 21 or 20 donepezil 21 or 21 or 22 placebo the total study duration for each patient is 78 weeks ( 18 months ) . 0 ###LEFT-WALL### 4 duration 0 ###LEFT-WALL### 8 is 0 ###LEFT-WALL### 15 . 1 the 4 duration 2 total 3 study 3 study 4 duration 4 duration 5 for 4 duration 8 is 5 for 7 patient 6 each 7 patient 8 is 10 weeks 9 78 10 weeks 10 weeks 13 months 11 ( 13 months 12 18 13 months 13 months 14 ) eighty dep - ci outpatients ( age 55 to 95 years ) are recruited : 40 at new york state psychiatric institute/columbia university and [40] at duke university medical center . 0 ###LEFT-WALL### 2 dep 0 ###LEFT-WALL### 13 are 0 ###LEFT-WALL### 15 : 0 ###LEFT-WALL### 31 . 1 eighty 2 dep 2 dep 5 outpatients 2 dep 13 are 3 - 5 outpatients 4 ci 5 outpatients 5 outpatients 11 years 5 outpatients 12 ) 6 ( 11 years 7 age 9 to 7 age 11 years 8 55 9 to 9 to 10 95 11 years 12 ) 13 are 14 recruited 15 : 16 40 16 40 24 and 17 at 23 university 17 at 24 and 18 new 19 york 19 york 20 state 20 state 21 psychiatric 21 psychiatric 22 institute/columbia 22 institute/columbia 23 university 24 and 26 at 26 at 30 center 27 duke 28 university 28 university 29 medical 29 medical 30 center the primary outcome is conversion to a clinical diagnosis of dementia . 0 ###LEFT-WALL### 3 outcome 0 ###LEFT-WALL### 4 is 0 ###LEFT-WALL### 12 . 1 the 3 outcome 2 primary 3 outcome 3 outcome 4 is 4 is 5 conversion 5 conversion 6 to 6 to 9 diagnosis 7 a 8 clinical 7 a 9 diagnosis 8 clinical 9 diagnosis 9 diagnosis 10 of 10 of 11 dementia the secondary outcomes are cognitive change scores in selective reminding test ( srt ) total recall and the modified alzheimer 's disease assessment scale ( adas - cog ) . 0 ###LEFT-WALL### 3 outcomes 0 ###LEFT-WALL### 4 are 0 ###LEFT-WALL### 30 . 1 the 3 outcomes 2 secondary 3 outcomes 3 outcomes 4 are 4 are 7 scores 5 cognitive 6 change 6 change 7 scores 7 scores 8 in 8 in 17 and 9 selective 10 reminding 10 reminding 11 test 11 test 13 srt 12 ( 13 srt 13 srt 14 ) 13 srt 15 total 15 total 16 recall 16 recall 17 and 17 and 28 cog 17 and 29 ) 18 the 20 alzheimer 19 modified 20 alzheimer 20 alzheimer 21 's 21 's 28 cog 22 disease 23 assessment 23 assessment 24 scale 24 scale 26 adas 25 ( 26 adas 26 adas 27 - 26 adas 28 cog other key assessments include the 24 - item hamilton depression rating scale and antidepressant response ; clinical global impression ( cgi ) for depression , cognition , and global status ; neuropsychological test battery [for] diagnosis ; informant report of functional abilities ( pfeffer faq ) [;] and treatment emergent symptom scale ( tess ) for somatic side effects . 0 ###LEFT-WALL### 3 assessments 0 ###LEFT-WALL### 4 include 0 ###LEFT-WALL### 16 ; 0 ###LEFT-WALL### 60 . 1 other 3 assessments 2 key 3 assessments 3 assessments 4 include 4 include 6 24 5 the 6 24 6 24 13 and 7 - 13 and 8 item 12 scale 9 hamilton 10 depression 10 depression 11 rating 11 rating 12 scale 12 scale 13 and 13 and 15 response 13 and 16 ; 14 antidepressant 15 response 16 ; 28 and 16 ; 31 ; 17 clinical 18 global 18 global 19 impression 19 impression 21 cgi 20 ( 21 cgi 21 cgi 22 ) 21 cgi 23 for 21 cgi 25 , 23 for 24 depression 25 , 26 cognition 25 , 28 and 27 , 28 and 28 and 30 status 29 global 30 status 31 ; 36 diagnosis 31 ; 37 ; 32 neuropsychological 33 test 33 test 34 battery 34 battery 36 diagnosis 37 ; 48 and 38 informant 39 report 39 report 40 of 39 report 48 and 40 of 42 abilities 41 functional 42 abilities 42 abilities 45 faq 43 ( 45 faq 44 pfeffer 45 faq 45 faq 46 ) 48 and 54 tess 48 and 56 for 49 treatment 50 emergent 50 emergent 51 symptom 51 symptom 52 scale 52 scale 54 tess 53 ( 54 tess 54 tess 55 ) 56 for 59 effects 57 somatic 58 side 58 side 59 effects apolipoprotein e ε4 status , odor identification deficits , and mri entorhinal/hippocampal cortex atrophy at baseline are evaluated as neurobiological moderators of donepezil treatment effects . 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 18 evaluated 0 ###LEFT-WALL### 26 . 1 apolipoprotein 2 e 1 apolipoprotein 4 status 3 ε4 4 status 4 status 5 , 5 , 8 deficits 5 , 10 and 6 odor 7 identification 7 identification 8 deficits 9 , 10 and 10 and 14 atrophy 10 and 17 are 11 mri 14 atrophy 12 entorhinal/hippocampal 13 cortex 13 cortex 14 atrophy 14 atrophy 15 at 15 at 16 baseline 17 are 18 evaluated 18 evaluated 19 as 19 as 21 moderators 20 neurobiological 21 moderators 21 moderators 22 of 21 moderators 24 treatment 21 moderators 25 effects 22 of 23 donepezil 24 treatment 25 effects immune responses to pathogens to which they were not previously exposed are commonly less effective in elderly people than in young adults , whereas those to agents previously encountered and overcome in earlier life may be amplified . 0 ###LEFT-WALL### 1 immune 0 ###LEFT-WALL### 12 are 0 ###LEFT-WALL### 23 , 0 ###LEFT-WALL### 38 . 1 immune 12 are 2 responses 3 to 2 responses 5 to 2 responses 12 are 3 to 4 pathogens 5 to 6 which 5 to 7 they 5 to 11 exposed 7 they 8 were 8 were 9 not 8 were 11 exposed 10 previously 11 exposed 12 are 13 commonly 12 are 15 effective 14 less 15 effective 15 effective 16 in 15 effective 19 than 16 in 18 people 17 elderly 18 people 19 than 20 in 20 in 22 adults 21 young 22 adults 23 , 34 life 23 , 36 be 24 whereas 25 those 24 whereas 34 life 25 those 26 to 25 those 30 and 26 to 27 agents 28 previously 29 encountered 29 encountered 30 and 30 and 31 overcome 30 and 32 in 30 and 33 earlier 34 life 35 may 35 may 36 be 36 be 37 amplified this [is] reflected in the robust finding in many studies that the proportions and numbers of [naïve] b and t cells are lower and memory cells higher in the elderly . 0 ###LEFT-WALL### 24 and 0 ###LEFT-WALL### 31 . 1 this 3 reflected 1 this 24 and 3 reflected 4 in 3 reflected 8 in 4 in 7 finding 5 the 7 finding 6 robust 7 finding 8 in 10 studies 9 many 10 studies 10 studies 11 that 10 studies 23 lower 11 that 21 cells 11 that 23 lower 12 the 13 proportions 13 proportions 14 and 14 and 15 numbers 14 and 16 of 14 and 19 and 16 of 18 b 19 and 20 t 19 and 21 cells 21 cells 22 are 22 are 23 lower 24 and 26 cells 25 memory 26 cells 26 cells 27 higher 27 higher 28 in 28 in 30 elderly 29 the 30 elderly in addition to the " extrinsic " effects of pathogen exposure , " intrinsic " events such as age - associated differences in haematopoeitic stem cells and their niches in the bone marrow associated with differences in cell maturation and output to the periphery are also observed . 0 ###LEFT-WALL### 27 and 0 ###LEFT-WALL### 47 observed 0 ###LEFT-WALL### 48 . 1 in 2 addition 1 in 20 - 1 in 27 and 2 addition 3 to 2 addition 16 events 3 to 8 effects 4 the 5 " 4 the 8 effects 6 extrinsic 7 " 6 extrinsic 8 effects 8 effects 9 of 9 of 11 exposure 10 pathogen 11 exposure 12 , 13 " 12 , 16 events 14 intrinsic 15 " 14 intrinsic 16 events 16 events 18 as 16 events 20 - 17 such 18 as 18 as 19 age 21 associated 22 differences 22 differences 23 in 22 differences 27 and 23 in 26 cells 24 haematopoeitic 25 stem 25 stem 26 cells 27 and 29 niches 27 and 30 in 27 and 34 associated 27 and 45 are 28 their 29 niches 30 in 33 marrow 31 the 33 marrow 32 bone 33 marrow 34 associated 35 with 34 associated 37 in 35 with 36 differences 37 in 40 and 38 cell 39 maturation 39 maturation 40 and 40 and 41 output 40 and 42 to 42 to 44 periphery 43 the 44 periphery 45 are 46 also 45 are 47 observed in the case of t cells , the " intrinsic " process of thymic [involution] , beginning before puberty , further [contributes] to reducing the production of [naïve] t cells . 0 ###LEFT-WALL### 6 cells 0 ###LEFT-WALL### 21 further 0 ###LEFT-WALL### 31 . 1 in 3 case 1 in 6 cells 2 the 3 case 3 case 4 of 4 of 5 t 6 cells 12 process 6 cells 21 further 7 , 12 process 8 the 9 " 8 the 12 process 10 intrinsic 11 " 10 intrinsic 12 process 12 process 13 of 12 process 20 , 13 of 17 beginning 14 thymic 16 , 14 thymic 17 beginning 17 beginning 18 before 18 before 19 puberty 21 further 23 to 21 further 30 cells 23 to 24 reducing 24 reducing 26 production 25 the 26 production 26 production 27 of 27 of 29 t like memory t cell populations [,] innate immune cells may be increased in number but decreased in efficacy on a [per] [-] cell basis . 0 ###LEFT-WALL### 15 but 0 ###LEFT-WALL### 25 . 1 like 2 memory 1 like 15 but 2 memory 3 t 2 memory 5 populations 2 memory 14 number 4 cell 5 populations 5 populations 9 cells 5 populations 13 in 5 populations 14 number 7 innate 9 cells 8 immune 9 cells 9 cells 10 may 10 may 11 be 11 be 12 increased 12 increased 13 in 15 but 16 decreased 16 decreased 17 in 16 decreased 19 on 17 in 18 efficacy 19 on 24 basis 20 a 24 basis 23 cell 24 basis thus , superimposed on chronological age alone , remodelling of immunity as a result of interactions with the environment over the life course is instrumental in shaping immune status in later life . 0 ###LEFT-WALL### 9 remodelling 0 ###LEFT-WALL### 24 is 0 ###LEFT-WALL### 33 . 1 thus 2 , 1 thus 9 remodelling 2 , 3 superimposed 3 superimposed 4 on 3 superimposed 7 alone 3 superimposed 8 , 3 superimposed 9 remodelling 4 on 6 age 5 chronological 6 age 9 remodelling 10 of 9 remodelling 24 is 10 of 11 immunity 11 immunity 12 as 12 as 14 result 13 a 14 result 14 result 15 of 15 of 16 interactions 16 interactions 17 with 17 with 19 environment 18 the 19 environment 19 environment 20 over 20 over 23 course 21 the 23 course 22 life 23 course 24 is 25 instrumental 25 instrumental 26 in 25 instrumental 30 in 26 in 27 shaping 27 shaping 29 status 28 immune 29 status 30 in 32 life 31 later 32 life in addition to interactions with pathogens , host microbiome and nutrition , exercise and stress , and many other extrinsic factors are crucial modulators of this " immunosenescence " process . 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 22 are 0 ###LEFT-WALL### 31 . 1 in 2 addition 1 in 12 , 1 in 17 and 2 addition 3 to 2 addition 5 with 3 to 4 interactions 5 with 10 and 6 pathogens 7 , 7 , 9 microbiome 7 , 10 and 8 host 9 microbiome 10 and 11 nutrition 13 exercise 14 and 14 and 15 stress 14 and 17 and 16 , 17 and 17 and 21 factors 17 and 22 are 18 many 19 other 19 other 21 factors 20 extrinsic 21 factors 22 are 24 modulators 23 crucial 24 modulators 24 modulators 25 of 25 of 30 process 26 this 27 " 26 this 30 process 28 immunosenescence 29 " 28 immunosenescence 30 process in this review , we briefly outline the observed immune differences between younger and older people , and discuss the possible impacts of behavioral variations thereon . 0 ###LEFT-WALL### 5 we 0 ###LEFT-WALL### 18 and 0 ###LEFT-WALL### 27 . 1 in 3 review 1 in 4 , 1 in 5 we 2 this 3 review 5 we 18 and 6 briefly 7 outline 7 outline 11 differences 7 outline 12 between 7 outline 18 and 8 the 11 differences 9 observed 11 differences 10 immune 11 differences 12 between 16 people 13 younger 14 and 14 and 15 older 14 and 16 people 17 , 18 and 18 and 19 discuss 19 discuss 22 impacts 19 discuss 26 thereon 20 the 22 impacts 21 possible 22 impacts 22 impacts 23 of 23 of 25 variations 24 behavioral 25 variations objectives : this study sought to define the relationship [between] body mass index ( bmi ) and mortality in heart failure ( hf ) across the world and to [identify] specific groups in whom bmi may differentially mediate risk . 0 ###LEFT-WALL### 1 objectives 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 40 . 2 : 17 and 3 this 4 study 4 study 5 sought 4 study 17 and 5 sought 6 to 6 to 7 define 7 define 13 index 8 the 13 index 9 relationship 11 body 11 body 12 mass 12 mass 13 index 13 index 15 bmi 14 ( 15 bmi 15 bmi 16 ) 17 and 18 mortality 17 and 19 in 17 and 28 and 19 in 21 failure 20 heart 21 failure 21 failure 23 hf 22 ( 23 hf 23 hf 24 ) 25 across 27 world 25 across 28 and 26 the 27 world 28 and 29 to 29 to 32 groups 31 specific 32 groups 32 groups 33 in 33 in 34 whom 33 in 35 bmi 33 in 38 mediate 35 bmi 36 may 36 may 38 mediate 37 differentially 38 mediate 38 mediate 39 risk background : obesity is associated with incident hf , but it is paradoxically associated with better prognosis [during] chronic hf . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 3 obesity 2 : 5 associated 2 : 10 but 2 : 21 . 3 obesity 4 is 4 is 5 associated 5 associated 6 with 6 with 8 hf 7 incident 8 hf 9 , 10 but 10 but 11 it 10 but 14 associated 11 it 12 is 12 is 14 associated 13 paradoxically 14 associated 14 associated 15 with 15 with 20 hf 16 better 17 prognosis 17 prognosis 20 hf 19 chronic 20 hf methods : we studied 6,142 patients with acute [decompensated] hf from 12 prospective observational cohorts followed - up across 4 continents . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 3 we 2 : 4 studied 2 : 22 . 3 we 4 studied 4 studied 6 patients 4 studied 7 with 4 studied 19 across 5 6,142 6 patients 7 with 10 hf 7 with 18 up 8 acute 10 hf 10 hf 11 from 11 from 15 cohorts 12 12 15 cohorts 13 prospective 15 cohorts 14 observational 15 cohorts 15 cohorts 16 followed 17 - 18 up 19 across 21 continents 20 4 21 continents primary [outcome] was all - cause mortality . 0 ###LEFT-WALL### 1 primary 0 ###LEFT-WALL### 3 was 0 ###LEFT-WALL### 5 - 1 primary 3 was 3 was 4 all 5 - 6 cause 5 - 8 . 6 cause 7 mortality cox proportional hazards models and net reclassification index described associations of bmi with all - cause mortality . 0 ###LEFT-WALL### 1 cox 0 ###LEFT-WALL### 15 - 1 cox 3 hazards 1 cox 13 with 2 proportional 3 hazards 3 hazards 5 and 3 hazards 8 index 4 models 5 and 5 and 7 reclassification 5 and 8 index 6 net 7 reclassification 8 index 10 associations 9 described 10 associations 10 associations 11 of 11 of 12 bmi 13 with 14 all 15 - 16 cause 15 - 18 . 16 cause 17 mortality results : normal - weight patients ( bmi 18.5 to 25 kg/m ( 2 ) ) were older with more advanced hf and lower cardiometabolic risk . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 27 . 2 : 6 patients 2 : 23 and 3 normal 4 - 3 normal 5 weight 5 weight 6 patients 6 patients 8 bmi 6 patients 23 and 7 ( 8 bmi 8 bmi 9 18.5 8 bmi 10 to 8 bmi 14 2 8 bmi 16 ) 10 to 12 kg/m 11 25 12 kg/m 13 ( 14 2 14 2 15 ) 17 were 18 older 17 were 23 and 18 older 19 with 19 with 22 hf 20 more 22 hf 21 advanced 22 hf 23 and 24 lower 23 and 26 risk 25 cardiometabolic 26 risk despite worldwide heterogeneity in clinical features across obesity categories [,] a higher bmi remained associated with decreased 30 - day [and] 1 - year mortality [(] 11 % decrease at 30 days [;] 9 % decrease at 1 year per 5 kg/m ( 2 ) [;] p < 0.05 [ )(, after adjustment for clinical risk . 1 despite 3 heterogeneity 1 despite 9 categories 2 worldwide 3 heterogeneity 4 in 6 features 4 in 9 categories 5 clinical 6 features 6 features 7 across 7 across 8 obesity 9 categories 13 bmi 9 categories 16 with 9 categories 17 decreased 11 a 13 bmi 12 higher 13 bmi 13 bmi 14 remained 14 remained 15 associated 14 remained 16 with 17 decreased 18 30 17 decreased 23 - 19 - 23 - 20 day 22 1 20 day 23 - 22 1 23 - 23 - 29 decrease 24 year 29 decrease 25 mortality 29 decrease 27 11 28 % 28 % 29 decrease 29 decrease 30 at 29 decrease 37 at 30 at 32 days 31 30 32 days 32 days 35 % 32 days 36 decrease 34 9 35 % 35 % 36 decrease 37 at 39 year 38 1 39 year 39 year 40 per 39 year 44 2 39 year 48 < 40 per 42 kg/m 41 5 42 kg/m 43 ( 44 2 44 2 45 ) 47 p 48 < 48 < 49 0.05 49 0.05 52 after 51 )(, 52 after 52 after 53 adjustment 52 after 57 . 53 adjustment 54 for 54 for 56 risk 55 clinical 56 risk the bmi obtained at index admission provided effective 1 [-] year risk reclassification beyond current markers of clinical risk ( net reclassification index 0.119 , p < 0.001 ) . 0 ###LEFT-WALL### 2 bmi 0 ###LEFT-WALL### 7 provided 0 ###LEFT-WALL### 30 . 1 the 2 bmi 2 bmi 3 obtained 2 bmi 7 provided 3 obtained 4 at 4 at 6 admission 5 index 6 admission 7 provided 13 reclassification 8 effective 13 reclassification 9 1 11 year 11 year 13 reclassification 12 risk 13 reclassification 13 reclassification 14 beyond 13 reclassification 17 of 13 reclassification 23 index 13 reclassification 27 < 14 beyond 16 markers 15 current 16 markers 17 of 19 risk 18 clinical 19 risk 20 ( 23 index 21 net 22 reclassification 22 reclassification 23 index 23 index 24 0.119 23 index 25 , 26 p 27 < 27 < 28 0.001 27 < 29 ) conclusions : a lower bmi is associated with age , disease severity , and a higher risk of death in acute [decompensated] hf . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 5 bmi 2 : 7 associated 2 : 24 . 3 a 5 bmi 4 lower 5 bmi 5 bmi 6 is 6 is 7 associated 7 associated 8 with 7 associated 20 in 8 with 14 and 9 age 10 , 10 , 12 severity 10 , 14 and 11 disease 12 severity 13 , 14 and 14 and 17 risk 14 and 18 of 15 a 17 risk 16 higher 17 risk 18 of 19 death 20 in 23 hf 21 acute 23 hf the " obesity paradox " is confined to older persons , [with] decreased cardiac function , less cardiometabolic illness , and recent - onset hf , suggesting that aging , hf severity/chronicity , and metabolism may explain the obesity paradox . 0 ###LEFT-WALL### 4 paradox 0 ###LEFT-WALL### 6 is 0 ###LEFT-WALL### 41 . 1 the 2 " 1 the 4 paradox 3 obesity 4 paradox 4 paradox 5 " 4 paradox 6 is 6 is 7 confined 7 confined 8 to 8 to 21 and 9 older 10 persons 10 persons 11 , 11 , 15 function 11 , 16 , 13 decreased 15 function 14 cardiac 15 function 16 , 19 illness 16 , 21 and 17 less 19 illness 18 cardiometabolic 19 illness 20 , 21 and 21 and 25 hf 21 and 26 , 21 and 27 suggesting 22 recent 23 - 22 recent 25 hf 24 onset 25 hf 27 suggesting 34 and 27 suggesting 37 explain 28 that 29 aging 28 that 30 , 30 , 32 severity/chronicity 30 , 34 and 31 hf 32 severity/chronicity 33 , 34 and 34 and 35 metabolism 34 and 36 may 36 may 37 explain 37 explain 40 paradox 38 the 40 paradox 39 obesity 40 paradox goal - directed behavior is well - known to show declines in elderly individuals , possibly because of alterations in dopaminergic neural transmission . 0 ###LEFT-WALL### 4 behavior 0 ###LEFT-WALL### 5 is 1 goal 2 - 1 goal 4 behavior 3 directed 4 behavior 4 behavior 5 is 5 is 6 well 6 well 8 known 7 - 8 known 8 known 9 to 8 known 24 . 9 to 10 show 10 show 11 declines 10 show 12 in 10 show 18 of 12 in 14 individuals 13 elderly 14 individuals 15 , 16 possibly 15 , 18 of 17 because 18 of 18 of 19 alterations 18 of 24 . 19 alterations 20 in 20 in 23 transmission 21 dopaminergic 23 transmission 22 neural 23 transmission the dopaminergic system is modulated by a number of other different factors . 0 ###LEFT-WALL### 3 system 0 ###LEFT-WALL### 5 modulated 0 ###LEFT-WALL### 13 . 1 the 3 system 2 dopaminergic 3 system 3 system 4 is 4 is 5 modulated 5 modulated 6 by 6 by 12 factors 7 a 8 number 8 number 9 of 8 number 12 factors 9 of 12 factors 10 other 12 factors 11 different 12 factors one of these factors , which has attracted a considerable amount of interest in neurobiology , [but] has only rarely been examined with respect to its possible modulatory role for cognitive functions in elderly individuals , is latent toxoplasma gondii ( [t.] gondii ) infection . 0 ###LEFT-WALL### 1 one 0 ###LEFT-WALL### 36 , 0 ###LEFT-WALL### 46 . 1 one 2 of 1 one 6 which 1 one 36 , 2 of 4 factors 3 these 4 factors 5 , 6 which 6 which 7 has 6 which 16 , 7 has 8 attracted 8 attracted 11 amount 9 a 10 considerable 9 a 11 amount 10 considerable 11 amount 11 amount 12 of 12 of 13 interest 13 interest 14 in 14 in 15 neurobiology 18 has 21 been 18 has 36 , 19 only 21 been 20 rarely 21 been 21 been 22 examined 22 examined 23 with 22 examined 25 to 23 with 24 respect 25 to 29 role 26 its 29 role 27 possible 29 role 28 modulatory 29 role 29 role 30 for 30 for 32 functions 31 cognitive 32 functions 32 functions 33 in 33 in 35 individuals 34 elderly 35 individuals 36 , 37 is 36 , 45 infection 37 is 40 gondii 38 latent 40 gondii 39 toxoplasma 40 gondii 40 gondii 43 gondii 41 ( 43 gondii 43 gondii 44 ) latent [t.] gondii infection may be of relevance [to] goal [-] directed behavior as it alters dopaminergic neural transmission . 0 ###LEFT-WALL### 1 latent 0 ###LEFT-WALL### 20 . 1 latent 4 infection 1 latent 6 be 1 latent 7 of 1 latent 16 alters 3 gondii 4 infection 4 infection 5 may 5 may 6 be 7 of 13 behavior 8 relevance 12 directed 10 goal 12 directed 12 directed 13 behavior 13 behavior 14 as 14 as 15 it 16 alters 19 transmission 17 dopaminergic 19 transmission 18 neural 19 transmission we examine goal [-] directed behavior in t . gondii igg positive and negative elderly subjects in auditory distraction paradigm . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 examine 0 ###LEFT-WALL### 9 . 1 we 2 examine 2 examine 6 behavior 2 examine 7 in 3 goal 5 directed 5 directed 6 behavior 7 in 8 t 9 . 20 paradigm 9 . 21 . 10 gondii 20 paradigm 11 igg 20 paradigm 12 positive 13 and 13 and 16 subjects 13 and 17 in 13 and 20 paradigm 14 negative 16 subjects 15 elderly 16 subjects 17 in 19 distraction 18 auditory 19 distraction we apply [event] - related potentials to examine which cognitive subprocesses are affected by latent [t.] gondii infection on a neurophysiological level . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 apply 0 ###LEFT-WALL### 5 related 0 ###LEFT-WALL### 23 . 1 we 2 apply 4 - 5 related 5 related 6 potentials 5 related 7 to 7 to 8 examine 8 examine 9 which 8 examine 19 on 9 which 11 subprocesses 10 cognitive 11 subprocesses 11 subprocesses 12 are 12 are 13 affected 13 affected 14 by 14 by 18 infection 15 latent 17 gondii 17 gondii 18 infection 19 on 22 level 20 a 21 neurophysiological 20 a 22 level 21 neurophysiological 22 level we show that latent [t.] gondii infection compromises the management of auditory distraction in elderly by specifically delaying processes of attentional allocation and disengagement . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 show 0 ###LEFT-WALL### 25 . 1 we 2 show 2 show 8 compromises 2 show 10 management 2 show 14 in 3 that 4 latent 4 latent 6 gondii 6 gondii 8 compromises 7 infection 8 compromises 9 the 10 management 10 management 11 of 11 of 13 distraction 12 auditory 13 distraction 14 in 23 and 15 elderly 16 by 15 elderly 23 and 16 by 18 delaying 17 specifically 18 delaying 18 delaying 19 processes 19 processes 20 of 20 of 22 allocation 21 attentional 22 allocation 23 and 24 disengagement the results show that [latent] t . gondii infection is neglected but an important neurobiological modulator of cognitive functions in elderly individuals . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 show 0 ###LEFT-WALL### 7 . 1 the 2 results 2 results 3 show 3 show 4 that 3 show 6 t 7 . 9 infection 7 . 11 neglected 7 . 23 . 8 gondii 9 infection 9 infection 10 is 10 is 11 neglected 11 neglected 12 but 11 neglected 20 in 12 but 16 modulator 13 an 14 important 13 an 16 modulator 14 important 16 modulator 15 neurobiological 16 modulator 16 modulator 17 of 17 of 19 functions 18 cognitive 19 functions 20 in 22 individuals 21 elderly 22 individuals reprogramming somatic cells to induced pluripotent stem cells ( ipscs ) resets their identity back to an embryonic age and , thus , presents a significant hurdle for modeling late - onset disorders . 0 ###LEFT-WALL### 1 reprogramming 0 ###LEFT-WALL### 20 and 0 ###LEFT-WALL### 34 . 1 reprogramming 3 cells 1 reprogramming 20 and 2 somatic 3 cells 3 cells 4 to 3 cells 10 ipscs 4 to 8 cells 5 induced 6 pluripotent 6 pluripotent 8 cells 7 stem 8 cells 9 ( 10 ipscs 10 ipscs 11 ) 12 resets 14 identity 12 resets 15 back 12 resets 16 to 12 resets 20 and 13 their 14 identity 16 to 19 age 17 an 18 embryonic 17 an 19 age 18 embryonic 19 age 20 and 24 presents 21 , 22 thus 22 thus 23 , 22 thus 24 presents 24 presents 27 hurdle 25 a 26 significant 25 a 27 hurdle 26 significant 27 hurdle 27 hurdle 28 for 28 for 33 disorders 29 modeling 33 disorders 30 late 31 - 30 late 32 onset 32 onset 33 disorders in this study , we describe a strategy for inducing aging - related features in human ipsc - derived lineages and apply it to the modeling of parkinson 's disease ( pd ) . 0 ###LEFT-WALL### 5 we 0 ###LEFT-WALL### 21 and 0 ###LEFT-WALL### 34 . 1 in 3 study 1 in 4 , 1 in 5 we 2 this 3 study 5 we 21 and 6 describe 8 strategy 6 describe 9 for 6 describe 21 and 7 a 8 strategy 9 for 10 inducing 10 inducing 20 lineages 11 aging 20 lineages 12 - 13 related 13 related 14 features 13 related 18 - 13 related 19 derived 14 features 15 in 15 in 17 ipsc 16 human 17 ipsc 19 derived 20 lineages 21 and 22 apply 21 and 24 to 22 apply 23 it 24 to 26 modeling 25 the 26 modeling 26 modeling 27 of 26 modeling 32 pd 27 of 30 disease 28 parkinson 29 's 29 's 30 disease 31 ( 32 pd 32 pd 33 ) our approach involves expression of progerin , a truncated form of lamin a associated with premature aging . 0 ###LEFT-WALL### 2 approach 0 ###LEFT-WALL### 3 involves 0 ###LEFT-WALL### 7 , 0 ###LEFT-WALL### 18 . 1 our 2 approach 2 approach 3 involves 3 involves 4 expression 4 expression 5 of 5 of 6 progerin 7 , 10 form 7 , 14 associated 8 a 10 form 9 truncated 10 form 10 form 11 of 10 form 14 associated 11 of 12 lamin 12 lamin 13 a 14 associated 15 with 15 with 17 aging 16 premature 17 aging we found that expression of progerin in ipsc - derived fibroblasts and neurons induces multiple aging - related markers and characteristics , including dopamine - [specific] [phenotypes] such as neuromelanin accumulation . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 found 0 ###LEFT-WALL### 18 related 0 ###LEFT-WALL### 32 . 1 we 2 found 2 found 4 expression 2 found 14 induces 3 that 4 expression 4 expression 5 of 4 expression 14 induces 5 of 12 and 6 progerin 7 in 6 progerin 12 and 7 in 11 fibroblasts 8 ipsc 9 - 8 ipsc 11 fibroblasts 10 derived 11 fibroblasts 12 and 13 neurons 14 induces 16 aging 15 multiple 16 aging 17 - 18 related 18 related 20 and 18 related 23 including 18 related 29 as 19 markers 20 and 20 and 21 characteristics 22 , 23 including 23 including 24 dopamine 23 including 25 - 28 such 29 as 29 as 31 accumulation 30 neuromelanin 31 accumulation induced aging in pd ipsc - derived dopamine neurons revealed disease phenotypes that require both aging and genetic susceptibility , such as pronounced dendrite degeneration , progressive loss of tyrosine hydroxylase ( th ) [expression] , and enlarged mitochondria or lewy - body - precursor inclusions . 0 ###LEFT-WALL### 37 and 0 ###LEFT-WALL### 42 - 0 ###LEFT-WALL### 47 . 1 induced 2 aging 1 induced 3 in 1 induced 37 and 3 in 17 and 4 pd 16 aging 4 pd 17 and 5 ipsc 6 - 5 ipsc 8 dopamine 7 derived 8 dopamine 8 dopamine 9 neurons 9 neurons 10 revealed 9 neurons 11 disease 9 neurons 12 phenotypes 9 neurons 14 require 11 disease 12 phenotypes 12 phenotypes 13 that 14 require 15 both 14 require 16 aging 15 both 16 aging 17 and 19 susceptibility 17 and 22 as 17 and 28 loss 18 genetic 19 susceptibility 20 , 22 as 21 such 22 as 22 as 25 degeneration 22 as 26 , 23 pronounced 24 dendrite 24 dendrite 25 degeneration 26 , 28 loss 27 progressive 28 loss 28 loss 29 of 28 loss 33 th 28 loss 36 , 29 of 31 hydroxylase 30 tyrosine 31 hydroxylase 32 ( 33 th 33 th 34 ) 37 and 38 enlarged 38 enlarged 40 or 39 mitochondria 40 or 40 or 41 lewy 42 - 43 body 42 - 44 - 44 - 46 inclusions 45 precursor 46 inclusions thus , our study suggests that progerin - induced aging can be used to reveal late - onset age - related disease features in hipsc - based disease models . 0 ###LEFT-WALL### 4 study 0 ###LEFT-WALL### 5 suggests 0 ###LEFT-WALL### 30 . 1 thus 2 , 1 thus 4 study 3 our 4 study 4 study 5 suggests 5 suggests 6 that 6 that 7 progerin 6 that 27 based 7 progerin 20 - 7 progerin 27 based 8 - 20 - 9 induced 10 aging 10 aging 11 can 11 can 12 be 12 be 13 used 13 used 14 to 13 used 15 reveal 14 to 15 reveal 15 reveal 19 age 15 reveal 20 - 16 late 17 - 16 late 18 onset 18 onset 19 age 19 age 20 - 20 - 23 features 20 - 26 - 21 related 22 disease 22 disease 23 features 23 features 24 in 24 in 25 hipsc 27 based 29 models 28 disease 29 models the immaturity of neurons differentiated from human induced pluripotent stem cells ( hipscs ) presents difficulties for modeling late - onset neurodegenerative disorders such as parkinson 's disease . 0 ###LEFT-WALL### 2 immaturity 0 ###LEFT-WALL### 15 presents 0 ###LEFT-WALL### 29 . 1 the 2 immaturity 2 immaturity 3 of 2 immaturity 13 hipscs 2 immaturity 15 presents 3 of 4 neurons 4 neurons 5 differentiated 4 neurons 6 from 6 from 11 cells 7 human 8 induced 8 induced 9 pluripotent 9 pluripotent 11 cells 10 stem 11 cells 12 ( 13 hipscs 13 hipscs 14 ) 15 presents 16 difficulties 16 difficulties 17 for 17 for 18 modeling 18 modeling 23 disorders 18 modeling 25 as 19 late 20 - 19 late 21 onset 21 onset 23 disorders 22 neurodegenerative 23 disorders 24 such 25 as 25 as 28 disease 26 parkinson 27 's 27 's 28 disease [now] [,] miller [et] [al] . 0 ###LEFT-WALL### 3 miller 0 ###LEFT-WALL### 6 . [(] 2013 [ )(provide a strategy for inducing aging - related [phenotypes] in hipsc - derived neurons , enabling in vitro study of late - onset neurodegenerative diseases . 0 ###LEFT-WALL### 2 2013 0 ###LEFT-WALL### 4 )(provide 0 ###LEFT-WALL### 29 . 2 2013 4 )(provide 4 )(provide 6 strategy 4 )(provide 7 for 5 a 6 strategy 7 for 8 inducing 8 inducing 9 aging 8 inducing 19 enabling 8 inducing 23 of 9 aging 11 related 10 - 11 related 11 related 13 in 11 related 18 , 13 in 17 neurons 14 hipsc 15 - 14 hipsc 17 neurons 16 derived 17 neurons 19 enabling 21 vitro 19 enabling 22 study 20 in 21 vitro 23 of 28 diseases 24 late 25 - 24 late 26 onset 26 onset 28 diseases 27 neurodegenerative 28 diseases frontotemporal dementia was documented over a century ago . 0 ###LEFT-WALL### 2 dementia 0 ###LEFT-WALL### 4 documented 0 ###LEFT-WALL### 9 . 1 frontotemporal 2 dementia 2 dementia 3 was 3 was 4 documented 4 documented 8 ago 5 over 7 century 6 a 7 century 7 century 8 ago the last decade , however , has seen substantial changes in our conceptions of this increasingly recognized disorder . 0 ###LEFT-WALL### 3 decade 0 ###LEFT-WALL### 8 seen 0 ###LEFT-WALL### 19 . 1 the 2 last 1 the 3 decade 3 decade 7 has 4 , 5 however 5 however 6 , 5 however 7 has 7 has 8 seen 8 seen 10 changes 8 seen 11 in 9 substantial 10 changes 11 in 13 conceptions 12 our 13 conceptions 13 conceptions 14 of 14 of 18 disorder 15 this 18 disorder 16 increasingly 17 recognized 17 recognized 18 disorder different clinical variants have been delineated , the most [common] of which is the behavioral variant ( bvftd ) . 0 ###LEFT-WALL### 3 variants 0 ###LEFT-WALL### 6 delineated 0 ###LEFT-WALL### 7 , 0 ###LEFT-WALL### 20 . 1 different 3 variants 2 clinical 3 variants 3 variants 4 have 4 have 5 been 5 been 6 delineated 7 , 9 most 7 , 13 is 8 the 9 most 9 most 11 of 9 most 13 is 11 of 12 which 13 is 16 variant 14 the 16 variant 15 behavioral 16 variant 16 variant 18 bvftd 17 ( 18 bvftd 18 bvftd 19 ) updated diagnostic criteria have been established . 0 ###LEFT-WALL### 3 criteria 0 ###LEFT-WALL### 6 established 0 ###LEFT-WALL### 7 . 1 updated 3 criteria 2 diagnostic 3 criteria 3 criteria 4 have 4 have 5 been 5 been 6 established new histopathological findings and genetic etiologies have been discovered . 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 9 discovered 0 ###LEFT-WALL### 10 . 1 new 3 findings 2 histopathological 3 findings 3 findings 4 and 4 and 6 etiologies 4 and 7 have 5 genetic 6 etiologies 7 have 8 been 8 been 9 discovered research continues to uncover molecular mechanisms by which abnormal proteins accumulate in degenerating brain tissue . 0 ###LEFT-WALL### 1 research 0 ###LEFT-WALL### 2 continues 0 ###LEFT-WALL### 16 . 1 research 2 continues 2 continues 3 to 3 to 4 uncover 4 uncover 6 mechanisms 4 uncover 12 in 5 molecular 6 mechanisms 6 mechanisms 7 by 7 by 8 which 7 by 10 proteins 7 by 11 accumulate 9 abnormal 10 proteins 10 proteins 11 accumulate 12 in 15 tissue 13 degenerating 14 brain 14 brain 15 tissue novel neuroimaging techniques suggest that functional networks are diminished in bvftd that might be relevant to empathy and social behavior . 0 ###LEFT-WALL### 18 and 0 ###LEFT-WALL### 21 . 1 novel 9 diminished 1 novel 10 in 1 novel 18 and 2 neuroimaging 3 techniques 3 techniques 4 suggest 4 suggest 5 that 5 that 7 networks 5 that 9 diminished 6 functional 7 networks 7 networks 8 are 8 are 9 diminished 10 in 11 bvftd 11 bvftd 12 that 11 bvftd 13 might 12 that 13 might 13 might 14 be 14 be 15 relevant 15 relevant 16 to 16 to 17 empathy 18 and 20 behavior 19 social 20 behavior despite rapid advances in our understanding of bvftd , the disease is still under [-] recognized and commonly misdiagnosed . 0 ###LEFT-WALL### 11 disease 0 ###LEFT-WALL### 12 is 0 ###LEFT-WALL### 20 . 1 despite 3 advances 1 despite 9 , 1 despite 11 disease 2 rapid 3 advances 3 advances 4 in 4 in 6 understanding 5 our 6 understanding 6 understanding 7 of 7 of 8 bvftd 10 the 11 disease 11 disease 12 is 12 is 13 still 13 still 14 under 14 under 17 and 16 recognized 17 and 17 and 19 misdiagnosed 18 commonly 19 misdiagnosed the result is inappropriate patient care . 0 ###LEFT-WALL### 2 result 0 ###LEFT-WALL### 3 is 0 ###LEFT-WALL### 7 . 1 the 2 result 2 result 3 is 3 is 6 care 4 inappropriate 6 care 5 patient 6 care recognizing the various presentations of bvftd and its histological and genetic [subtypes] might further diagnosis , treatment , and research . 0 ###LEFT-WALL### 1 recognizing 0 ###LEFT-WALL### 19 and 0 ###LEFT-WALL### 21 . 1 recognizing 4 presentations 1 recognizing 13 might 2 the 4 presentations 3 various 4 presentations 4 presentations 5 of 5 of 10 and 6 bvftd 7 and 7 and 9 histological 7 and 10 and 8 its 9 histological 10 and 11 genetic 13 might 19 and 14 further 15 diagnosis 14 further 19 and 15 diagnosis 17 treatment 16 , 17 treatment 17 treatment 18 , 18 , 19 and 19 and 20 research reversible posttranslational modifications are emerging as critical regulators of mitochondrial proteins and metabolism . 0 ###LEFT-WALL### 3 modifications 0 ###LEFT-WALL### 4 are 0 ###LEFT-WALL### 14 . 1 reversible 3 modifications 2 posttranslational 3 modifications 3 modifications 4 are 4 are 8 regulators 5 emerging 8 regulators 6 as 7 critical 7 critical 8 regulators 8 regulators 9 of 9 of 12 and 10 mitochondrial 11 proteins 11 proteins 12 and 12 and 13 metabolism here , we use a label [-] free quantitative proteomic approach to characterize the lysine succinylome in liver mitochondria and its regulation by the desuccinylase sirt5 . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 use 0 ###LEFT-WALL### 27 . 1 here 2 , 1 here 3 we 3 we 4 use 4 use 11 approach 4 use 12 to 4 use 13 characterize 5 a 11 approach 6 label 11 approach 8 free 11 approach 9 quantitative 11 approach 10 proteomic 11 approach 12 to 13 characterize 13 characterize 15 lysine 13 characterize 23 by 14 the 15 lysine 15 lysine 16 succinylome 16 succinylome 17 in 17 in 20 and 18 liver 19 mitochondria 19 mitochondria 20 and 20 and 22 regulation 21 its 22 regulation 23 by 26 sirt5 24 the 25 desuccinylase 25 desuccinylase 26 sirt5 a total of 1,190 unique sites were identified as succinylated , and 386 sites across 140 proteins representing several metabolic pathways including β - oxidation and ketogenesis [were] significantly hypersuccinylated in sirt5 [(] - [/] - ) animals . 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 39 . 1 a 2 total 2 total 3 of 2 total 12 and 3 of 4 1,190 4 1,190 6 sites 4 1,190 10 succinylated 5 unique 6 sites 6 sites 7 were 7 were 8 identified 8 identified 9 as 9 as 10 succinylated 11 , 12 and 12 and 14 sites 12 and 15 across 12 and 18 representing 13 386 14 sites 15 across 17 proteins 16 140 17 proteins 18 representing 21 pathways 19 several 21 pathways 20 metabolic 21 pathways 21 pathways 22 including 22 including 38 animals 23 β 26 and 23 β 37 ) 23 β 38 animals 24 - 26 and 25 oxidation 26 and 26 and 27 ketogenesis 26 and 34 - 26 and 36 - 27 ketogenesis 30 hypersuccinylated 29 significantly 30 hypersuccinylated 30 hypersuccinylated 31 in 31 in 32 sirt5 loss of sirt5 leads to accumulation of medium - and long - chain acylcarnitines and decreased β - hydroxybutyrate production in vivo . 0 ###LEFT-WALL### 1 loss 0 ###LEFT-WALL### 4 leads 0 ###LEFT-WALL### 23 . 1 loss 2 of 1 loss 4 leads 2 of 3 sirt5 4 leads 5 to 5 to 6 accumulation 6 accumulation 7 of 7 of 10 and 8 medium 10 and 9 - 10 and 10 and 13 chain 11 long 12 - 11 long 13 chain 13 chain 15 and 14 acylcarnitines 15 and 15 and 16 decreased 15 and 20 production 15 and 22 vivo 16 decreased 19 hydroxybutyrate 17 β 18 - 17 β 19 hydroxybutyrate 21 in 22 vivo in addition , we demonstrate that sirt5 regulates succinylation of the rate - limiting ketogenic enzyme 3 - hydroxy - 3 - methylglutaryl - coa synthase 2 ( hmgcs2 ) [both] in vivo and in vitro . 0 ###LEFT-WALL### 4 we 0 ###LEFT-WALL### 5 demonstrate 0 ###LEFT-WALL### 18 - 0 ###LEFT-WALL### 19 hydroxy 0 ###LEFT-WALL### 37 . 1 in 2 addition 1 in 3 , 1 in 4 we 4 we 5 demonstrate 5 demonstrate 6 that 6 that 7 sirt5 6 that 8 regulates 7 sirt5 8 regulates 8 regulates 9 succinylation 9 succinylation 10 of 10 of 12 rate 11 the 12 rate 12 rate 14 limiting 13 - 14 limiting 14 limiting 16 enzyme 14 limiting 18 - 15 ketogenic 16 enzyme 16 enzyme 17 3 18 - 19 hydroxy 19 hydroxy 22 - 19 hydroxy 34 and 20 - 22 - 21 3 22 - 22 - 23 methylglutaryl 22 - 30 ) 23 methylglutaryl 26 synthase 24 - 26 synthase 25 coa 26 synthase 26 synthase 27 2 26 synthase 29 hmgcs2 26 synthase 30 ) 28 ( 29 hmgcs2 29 hmgcs2 30 ) 32 in 33 vivo 33 vivo 34 and 34 and 36 vitro 35 in 36 vitro finally , mutation of hypersuccinylated residues k83 and k310 on hmgcs2 to glutamic acid strongly inhibits enzymatic activity . 0 ###LEFT-WALL### 3 mutation 0 ###LEFT-WALL### 16 inhibits 0 ###LEFT-WALL### 19 . 1 finally 2 , 1 finally 3 mutation 3 mutation 4 of 3 mutation 16 inhibits 4 of 8 and 5 hypersuccinylated 6 residues 6 residues 7 k83 7 k83 8 and 8 and 9 k310 8 and 10 on 10 on 11 hmgcs2 11 hmgcs2 12 to 12 to 14 acid 13 glutamic 14 acid 15 strongly 16 inhibits 16 inhibits 18 activity 17 enzymatic 18 activity taken together , these findings establish sirt5 as a global regulator of lysine succinylation in mitochondria and present a mechanism for inhibition of ketogenesis through hmgcs2 . 0 ###LEFT-WALL### 5 findings 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 27 . 1 taken 2 together 1 taken 3 , 1 taken 5 findings 4 these 5 findings 5 findings 17 and 6 establish 7 sirt5 6 establish 8 as 6 establish 15 in 6 establish 17 and 8 as 11 regulator 9 a 10 global 9 a 11 regulator 10 global 11 regulator 11 regulator 12 of 12 of 14 succinylation 13 lysine 14 succinylation 15 in 16 mitochondria 17 and 18 present 17 and 25 through 18 present 20 mechanism 19 a 20 mechanism 20 mechanism 21 for 20 mechanism 23 of 21 for 22 inhibition 23 of 24 ketogenesis 25 through 26 hmgcs2 back pain episodes are traditionally regarded as individual events , but this model is currently being challenged in favour of treating back pain as a long - term or lifelong condition . 0 ###LEFT-WALL### 1 back 0 ###LEFT-WALL### 11 but 0 ###LEFT-WALL### 17 challenged 0 ###LEFT-WALL### 32 . 1 back 2 pain 2 pain 3 episodes 2 pain 4 are 2 pain 6 regarded 3 episodes 4 are 5 traditionally 6 regarded 6 regarded 7 as 6 regarded 10 , 7 as 9 events 8 individual 9 events 11 but 13 model 11 but 14 is 12 this 13 model 13 model 14 is 14 is 16 being 15 currently 16 being 16 being 17 challenged 17 challenged 18 in 18 in 29 or 19 favour 20 of 19 favour 29 or 20 of 21 treating 21 treating 22 back 21 treating 23 pain 21 treating 24 as 24 as 28 term 25 a 26 long 25 a 28 term 26 long 27 - 26 long 28 term 29 or 31 condition 30 lifelong 31 condition a number of factors predict back pain presence in epidemiological studies , and these are often present , and predictive , at different life stages . 0 ###LEFT-WALL### 4 factors 0 ###LEFT-WALL### 5 predict 1 a 2 number 2 number 3 of 2 number 4 factors 3 of 4 factors 4 factors 5 predict 5 predict 6 back 5 predict 13 and 5 predict 15 are 7 pain 8 presence 8 presence 9 in 8 presence 13 and 9 in 11 studies 10 epidemiological 11 studies 12 , 13 and 13 and 14 these 13 and 15 are 15 are 16 often 15 are 19 and 17 present 19 and 18 , 19 and 19 and 20 predictive 20 predictive 22 at 21 , 22 at 22 at 25 stages 22 at 26 . 23 different 24 life 24 life 25 stages there are also factors present at particular life stages , such as childhood or adolescence , which predict back pain in adulthood . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 are 0 ###LEFT-WALL### 23 . 1 there 2 are 2 are 3 also 2 are 4 factors 4 factors 5 present 4 factors 17 which 4 factors 18 predict 5 present 6 at 5 present 12 as 6 at 9 stages 7 particular 8 life 8 life 9 stages 10 , 12 as 11 such 12 as 12 as 14 or 12 as 16 , 13 childhood 14 or 14 or 15 adolescence 17 which 18 predict 18 predict 20 pain 18 predict 21 in 19 back 20 pain 21 in 22 adulthood however , there are little published data on long - term pain patterns or predictors over the life course . 0 ###LEFT-WALL### 3 there 0 ###LEFT-WALL### 4 are 0 ###LEFT-WALL### 20 . 1 however 2 , 1 however 3 there 3 there 4 are 4 are 7 data 4 are 8 on 4 are 16 over 5 little 7 data 6 published 7 data 8 on 14 or 9 long 10 - 9 long 11 term 11 term 13 patterns 12 pain 13 patterns 13 patterns 14 or 14 or 15 predictors 16 over 19 course 17 the 19 course 18 life 19 course such studies could improve our understanding of the development and fluctuations in back pain , and therefore influence treatment approaches . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 16 and 0 ###LEFT-WALL### 21 . 1 such 2 studies 2 studies 3 could 3 could 16 and 4 improve 6 understanding 4 improve 12 in 4 improve 16 and 5 our 6 understanding 6 understanding 7 of 7 of 10 and 8 the 9 development 9 development 10 and 10 and 11 fluctuations 12 in 14 pain 13 back 14 pain 15 , 16 and 16 and 18 influence 16 and 20 approaches 17 therefore 18 influence 18 influence 19 treatment objectives : examine the longitudinal course of posttraumatic stress disorder ( ptsd ) in older adults and its influence on mental health quality of life ( mhqol ) . 0 ###LEFT-WALL### 1 objectives 0 ###LEFT-WALL### 3 examine 0 ###LEFT-WALL### 29 . 1 objectives 2 : 2 : 3 examine 3 examine 6 course 3 examine 14 in 3 examine 20 on 4 the 6 course 5 longitudinal 6 course 6 course 7 of 7 of 10 disorder 8 posttraumatic 9 stress 9 stress 10 disorder 10 disorder 12 ptsd 11 ( 12 ptsd 12 ptsd 13 ) 14 in 17 and 15 older 16 adults 16 adults 17 and 17 and 19 influence 18 its 19 influence 20 on 23 quality 21 mental 22 health 22 health 23 quality 23 quality 24 of 24 of 25 life 25 life 27 mhqol 26 ( 27 mhqol 27 mhqol 28 ) design : evaluation performed at baseline , and 3 and 6 months postrandomization as part of a longitudinal trial . 0 ###LEFT-WALL### 1 design 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 20 . 2 : 3 evaluation 2 : 4 performed 3 evaluation 4 performed 4 performed 5 at 4 performed 14 as 5 at 8 and 6 baseline 8 and 7 , 8 and 8 and 13 postrandomization 9 3 10 and 10 and 11 6 10 and 12 months 12 months 13 postrandomization 14 as 15 part 15 part 16 of 16 of 19 trial 17 a 18 longitudinal 17 a 19 trial 18 longitudinal 19 trial participants and settings : a total of 1,185 participants , with a mean [(] [±sd] ) age [of] 73.53 ( ±5.98 ) years , at seven primary care sites ( including five veterans affairs clinics ) , [were] divided into four groups , namely , no trauma ( n = 661 ) , [trauma] only [(] n = 319 [ )( [partial] ptsd ( n = 114 ) , and ptsd ( n = 81 ) , based on reports of trauma and associated ptsd symptoms . 0 ###LEFT-WALL### 3 settings 0 ###LEFT-WALL### 4 : 1 participants 3 settings 2 and 3 settings 4 : 6 total 4 : 10 , 5 a 6 total 6 total 7 of 7 of 9 participants 8 1,185 9 participants 10 , 17 age 11 with 13 mean 11 with 16 ) 11 with 17 age 12 a 13 mean 17 age 19 73.53 17 age 25 at 19 73.53 23 years 20 ( 23 years 21 ±5.98 22 ) 21 ±5.98 23 years 23 years 24 , 25 at 29 sites 26 seven 28 care 27 primary 28 care 28 care 29 sites 29 sites 31 including 29 sites 39 divided 30 ( 31 including 31 including 35 clinics 31 including 36 ) 32 five 35 clinics 33 veterans 35 clinics 34 affairs 35 clinics 37 , 39 divided 39 divided 40 into 40 into 42 groups 41 four 42 groups 42 groups 44 namely 43 , 44 namely 44 namely 45 , 44 namely 47 trauma 46 no 47 trauma 47 trauma 50 = 47 trauma 58 = 48 ( 50 = 49 n 50 = 50 = 51 661 50 = 52 ) 53 , 55 only 53 , 58 = 57 n 58 = 58 = 70 and 59 319 70 and 63 ptsd 66 = 63 ptsd 70 and 64 ( 66 = 65 n 66 = 66 = 67 114 66 = 68 ) 69 , 70 and 70 and 71 ptsd 70 and 74 = 70 and 78 based 72 ( 74 = 73 n 74 = 74 = 75 81 74 = 76 ) 77 , 78 based 78 based 79 on 79 on 80 reports 80 reports 81 of 81 of 83 and 82 trauma 83 and 83 and 86 symptoms 83 and 87 . 84 associated 86 symptoms 85 ptsd 86 symptoms measurements : the prevalence of comorbid depression , anxiety , and alcohol use disorders , assessed using the diagnostic and statistical manual , fourth edition , criteria and changes in mhqol , as assessed by the short form - 36 mental component score . 0 ###LEFT-WALL### 1 measurements 0 ###LEFT-WALL### 2 : 2 : 11 and 2 : 13 use 2 : 23 , 2 : 39 - 3 the 4 prevalence 4 prevalence 5 of 4 prevalence 8 , 5 of 7 depression 6 comorbid 7 depression 8 , 9 anxiety 8 , 11 and 10 , 11 and 11 and 12 alcohol 11 and 13 use 13 use 14 disorders 13 use 16 assessed 15 , 16 assessed 16 assessed 17 using 16 assessed 23 , 17 using 22 manual 18 the 22 manual 19 diagnostic 20 and 20 and 21 statistical 21 statistical 22 manual 23 , 28 and 24 fourth 25 edition 25 edition 26 , 26 , 27 criteria 26 , 28 and 28 and 29 changes 28 and 35 by 29 changes 30 in 30 in 31 mhqol 31 mhqol 34 assessed 32 , 34 assessed 33 as 34 assessed 35 by 38 form 36 the 38 form 37 short 38 form 39 - 43 score 39 - 44 . 40 36 42 component 41 mental 42 component 42 component 43 score results : at baseline , the ptsd group had higher frequencies of comorbid depression and anxiety disorders and worse mhqol than the other groups . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 5 , 0 ###LEFT-WALL### 25 . 1 results 2 : 2 : 3 at 3 at 4 baseline 5 , 8 group 5 , 9 had 6 the 8 group 7 ptsd 8 group 8 group 9 had 9 had 18 and 9 had 21 than 10 higher 11 frequencies 11 frequencies 12 of 11 frequencies 15 and 12 of 14 depression 13 comorbid 14 depression 15 and 17 disorders 15 and 18 and 16 anxiety 17 disorders 18 and 20 mhqol 19 worse 20 mhqol 21 than 24 groups 22 the 23 other 23 other 24 groups both chronic [(] participants diagnosed with ptsd at all three assessments [ )(and fluctuating [(] participants moving to [or] [from] one of the other groups [ )(trajectories of course were observed during the [follow] [-] up period , which appeared to be separate from that of the comorbid disorders . 1 both 4 participants 2 chronic 4 participants 4 participants 5 diagnosed 5 diagnosed 6 with 5 diagnosed 8 at 5 diagnosed 16 participants 6 with 7 ptsd 8 at 9 all 10 three 16 participants 11 assessments 13 )(and 13 )(and 14 fluctuating 13 )(and 16 participants 16 participants 17 moving 17 moving 18 to 18 to 21 one 21 one 22 of 21 one 25 groups 21 one 31 observed 22 of 24 other 23 the 24 other 25 groups 27 )(trajectories 25 groups 30 were 25 groups 31 observed 27 )(trajectories 30 were 28 of 29 course 29 course 30 were 31 observed 32 during 32 during 37 period 33 the 37 period 36 up 37 period 37 period 39 which 38 , 39 which 39 which 40 appeared 39 which 50 . 40 appeared 41 to 40 appeared 42 be 41 to 42 be 42 be 43 separate 43 separate 44 from 44 from 45 that 45 that 46 of 46 of 49 disorders 47 the 49 disorders 48 comorbid 49 disorders even after accounting for those comorbid disorders , ptsd had an independent association with poorer mhqol at multiple time points , especially in men , whereas trauma without ptsd symptoms ( trauma [only] ) had better mhqol . 0 ###LEFT-WALL### 9 ptsd 0 ###LEFT-WALL### 10 had 0 ###LEFT-WALL### 25 , 0 ###LEFT-WALL### 38 . 1 even 2 after 1 even 9 ptsd 2 after 3 accounting 4 for 7 disorders 4 for 8 , 4 for 9 ptsd 5 those 7 disorders 6 comorbid 7 disorders 9 ptsd 10 had 10 had 13 association 10 had 14 with 10 had 17 at 11 an 13 association 12 independent 13 association 14 with 16 mhqol 15 poorer 16 mhqol 17 at 20 points 18 multiple 20 points 19 time 20 points 20 points 23 in 21 , 22 especially 21 , 23 in 23 in 24 men 23 in 25 , 25 , 36 better 26 whereas 27 trauma 26 whereas 36 better 27 trauma 28 without 27 trauma 30 symptoms 27 trauma 35 had 28 without 29 ptsd 30 symptoms 32 trauma 30 symptoms 35 had 31 ( 32 trauma 32 trauma 34 ) 36 better 37 mhqol conclusions : ptsd had chronic and fluctuating courses , with negative effects on mhqol , while partial ptsd might represent a transitional state , underscoring the need to better identify and treat ptsd at any phase in later life . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 40 . 2 : 3 ptsd 2 : 4 had 3 ptsd 4 had 4 had 31 and 4 had 34 at 5 chronic 6 and 6 and 8 courses 6 and 9 , 6 and 10 with 6 and 31 and 7 fluctuating 8 courses 10 with 12 effects 11 negative 12 effects 12 effects 13 on 12 effects 25 underscoring 13 on 14 mhqol 15 , 16 while 16 while 18 ptsd 16 while 20 represent 16 while 24 , 16 while 25 underscoring 17 partial 18 ptsd 18 ptsd 19 might 19 might 20 represent 20 represent 23 state 21 a 23 state 22 transitional 23 state 25 underscoring 27 need 26 the 27 need 27 need 28 to 27 need 30 identify 28 to 30 identify 29 better 30 identify 31 and 33 ptsd 32 treat 33 ptsd 34 at 36 phase 35 any 36 phase 36 phase 37 in 37 in 39 life 38 later 39 life none sarcopenia is a notable [and] debilitating age - associated condition . 0 ###LEFT-WALL### 1 none 0 ###LEFT-WALL### 8 age 0 ###LEFT-WALL### 9 - 0 ###LEFT-WALL### 12 . 1 none 2 sarcopenia 1 none 7 debilitating 1 none 8 age 2 sarcopenia 3 is 3 is 5 notable 4 a 5 notable 5 notable 7 debilitating 9 - 11 condition 10 associated 11 condition flavonoids are known for their healthy effects and limited toxicity . 0 ###LEFT-WALL### 1 flavonoids 0 ###LEFT-WALL### 3 known 0 ###LEFT-WALL### 11 . 1 flavonoids 2 are 2 are 3 known 3 known 4 for 4 for 8 and 5 their 7 effects 6 healthy 7 effects 7 effects 8 and 8 and 10 toxicity 9 limited 10 toxicity the flavanol [(] - [ )(- epicatechin ( epi ) enhances exercise capacity in mice , and epi - rich cocoa improves skeletal muscle structure in heart failure patients . [(] - [ )(- epicatechin may thus hold promise [as] treatment for sarcopenia . 0 ###LEFT-WALL### 2 flavanol 0 ###LEFT-WALL### 4 - 0 ###LEFT-WALL### 44 . 1 the 2 flavanol 4 - 6 )(- 4 - 11 enhances 4 - 19 - 4 - 38 hold 6 )(- 7 epicatechin 7 epicatechin 9 epi 7 epicatechin 11 enhances 8 ( 9 epi 9 epi 10 ) 11 enhances 13 capacity 11 enhances 14 in 12 exercise 13 capacity 14 in 17 and 15 mice 17 and 16 , 17 and 17 and 18 epi 19 - 21 cocoa 19 - 22 improves 19 - 30 . 20 rich 21 cocoa 21 cocoa 22 improves 22 improves 25 structure 23 skeletal 24 muscle 24 muscle 25 structure 25 structure 26 in 26 in 29 patients 27 heart 29 patients 28 failure 29 patients 30 . 32 - 32 - 34 )(- 34 )(- 35 epicatechin 35 epicatechin 36 may 36 may 38 hold 37 thus 38 hold 38 hold 41 treatment 38 hold 42 for 39 promise 41 treatment 42 for 43 sarcopenia we examined changes in protein levels of molecular modulators of growth and differentiation [in] young [vs] . old , human and mouse skeletal muscle . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 examined 0 ###LEFT-WALL### 17 . 0 ###LEFT-WALL### 25 . 1 we 2 examined 2 examined 3 changes 2 examined 4 in 2 examined 15 young 4 in 6 levels 5 protein 6 levels 6 levels 7 of 7 of 9 modulators 8 molecular 9 modulators 9 modulators 10 of 10 of 12 and 11 growth 12 and 12 and 13 differentiation 17 . 21 and 18 old 19 , 19 , 20 human 19 , 21 and 21 and 24 muscle 22 mouse 24 muscle 23 skeletal 24 muscle we report the effects of epi in mice and the results of an initial proof - of [-] concept trial [in] humans , where muscle strength and levels of modulators of muscle growth were measured . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 report 0 ###LEFT-WALL### 36 . 1 we 2 report 2 report 4 effects 2 report 7 in 2 report 24 where 3 the 4 effects 4 effects 5 of 5 of 6 epi 7 in 9 and 8 mice 9 and 9 and 11 results 9 and 12 of 9 and 17 of 10 the 11 results 12 of 15 proof 13 an 15 proof 14 initial 15 proof 16 - 17 of 17 of 22 humans 17 of 23 , 19 concept 20 trial 20 trial 22 humans 24 where 27 and 24 where 35 measured 25 muscle 26 strength 26 strength 27 and 27 and 28 levels 27 and 29 of 27 and 31 of 27 and 34 were 29 of 30 modulators 31 of 33 growth 32 muscle 33 growth 34 were 35 measured in mice , myostatin and senescence - associated β - galactosidase levels increase with aging , while those of follistatin and myf5 decrease [.] [(] - ) - epicatechin decreases myostatin and β - galactosidase and increases levels of markers of muscle growth . 0 ###LEFT-WALL### 29 epicatechin 0 ###LEFT-WALL### 30 decreases 1 in 5 and 1 in 29 epicatechin 2 mice 3 , 3 , 4 myostatin 3 , 5 and 5 and 6 senescence 5 and 9 β 7 - 9 β 8 associated 9 β 9 β 11 galactosidase 9 β 28 - 10 - 11 galactosidase 11 galactosidase 12 levels 11 galactosidase 13 increase 11 galactosidase 14 with 11 galactosidase 27 ) 12 levels 13 increase 14 with 15 aging 15 aging 17 while 16 , 17 while 17 while 18 those 17 while 23 decrease 17 while 26 - 18 those 19 of 18 those 23 decrease 19 of 21 and 20 follistatin 21 and 21 and 22 myf5 29 epicatechin 30 decreases 30 decreases 36 and 31 myostatin 32 and 32 and 35 galactosidase 32 and 36 and 33 β 34 - 33 β 35 galactosidase 36 and 38 levels 36 and 44 . 37 increases 38 levels 38 levels 39 of 39 of 40 markers 40 markers 41 of 41 of 43 growth 42 muscle 43 growth in humans , myostatin and β - galactosidase increase with aging while follistatin , myod and myogenin decrease . 0 ###LEFT-WALL### 5 and 0 ###LEFT-WALL### 9 increase 0 ###LEFT-WALL### 19 . 1 in 2 humans 1 in 3 , 1 in 5 and 4 myostatin 5 and 5 and 8 galactosidase 5 and 9 increase 6 β 7 - 6 β 8 galactosidase 9 increase 10 with 10 with 11 aging 11 aging 12 while 12 while 16 and 12 while 18 decrease 13 follistatin 14 , 14 , 15 myod 14 , 16 and 16 and 17 myogenin 16 and 18 decrease treatment for 7 days with [(] [-] [ )( epicatechin increases hand grip strength and the ratio of plasma follistatin/myostatin . 0 ###LEFT-WALL### 15 and 0 ###LEFT-WALL### 21 . 1 treatment 2 for 1 treatment 15 and 2 for 4 days 3 7 4 days 4 days 11 increases 4 days 12 hand 5 with 10 epicatechin 5 with 11 increases 11 increases 12 hand 12 hand 14 strength 13 grip 14 strength 15 and 17 ratio 15 and 18 of 16 the 17 ratio 18 of 20 follistatin/myostatin 19 plasma 20 follistatin/myostatin in conclusion , aging has deleterious effects on modulators of muscle growth/differentiation , and the consumption of modest amounts of the flavanol [(] - [ )(- epicatechin can partially reverse these changes . 0 ###LEFT-WALL### 2 conclusion 0 ###LEFT-WALL### 3 , 1 in 2 conclusion 3 , 4 aging 3 , 5 has 3 , 24 - 4 aging 5 has 5 has 7 effects 5 has 8 on 6 deleterious 7 effects 8 on 9 modulators 9 modulators 10 of 9 modulators 17 of 10 of 14 and 11 muscle 12 growth/differentiation 12 growth/differentiation 14 and 13 , 14 and 14 and 16 consumption 15 the 16 consumption 17 of 19 amounts 18 modest 19 amounts 19 amounts 20 of 20 of 22 flavanol 21 the 22 flavanol 24 - 26 )(- 24 - 30 reverse 24 - 33 . 26 )(- 27 epicatechin 27 epicatechin 28 can 28 can 30 reverse 29 partially 30 reverse 30 reverse 32 changes 31 these 32 changes this flavanol warrants its comprehensive evaluation for the treatment of sarcopenia . 0 ###LEFT-WALL### 2 flavanol 0 ###LEFT-WALL### 3 warrants 0 ###LEFT-WALL### 12 . 1 this 2 flavanol 2 flavanol 3 warrants 3 warrants 6 evaluation 4 its 6 evaluation 5 comprehensive 6 evaluation 6 evaluation 7 for 7 for 9 treatment 8 the 9 treatment 9 treatment 10 of 10 of 11 sarcopenia purpose : quantifying the extent of conjunctival fibrosis [for] documentation of progression in conjunctival scarring disease is a clinical challenge . 0 ###LEFT-WALL### 1 purpose 0 ###LEFT-WALL### 2 : 2 : 3 quantifying 2 : 17 is 2 : 21 . 3 quantifying 5 extent 3 quantifying 13 in 3 quantifying 17 is 4 the 5 extent 5 extent 6 of 6 of 10 documentation 7 conjunctival 8 fibrosis 8 fibrosis 10 documentation 10 documentation 11 of 11 of 12 progression 13 in 16 disease 14 conjunctival 16 disease 15 scarring 16 disease 17 is 20 challenge 18 a 19 clinical 18 a 20 challenge 19 clinical 20 challenge measurement of forniceal foreshortening facilitates monitoring of these disorders . 0 ###LEFT-WALL### 1 measurement 0 ###LEFT-WALL### 5 facilitates 0 ###LEFT-WALL### 10 . 1 measurement 2 of 1 measurement 5 facilitates 2 of 4 foreshortening 3 forniceal 4 foreshortening 5 facilitates 6 monitoring 6 monitoring 7 of 7 of 9 disorders 8 these 9 disorders [this] study aims ( 1 ) to define the limits of the normal human conjunctival fornices and how these alter with age [and] ( 2 ) to provide normative data for upper and lower fornix depths ( fds ) and fornix intercanthal distance ( ficd ) within a healthy south asian , racially distinct population . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 28 provide 2 study 3 aims 2 study 7 to 3 aims 5 1 4 ( 5 1 5 1 6 ) 7 to 8 define 8 define 10 limits 9 the 10 limits 10 limits 11 of 11 of 16 fornices 12 the 16 fornices 13 normal 16 fornices 14 human 16 fornices 15 conjunctival 16 fornices 17 and 18 how 17 and 20 alter 19 these 20 alter 20 alter 21 with 20 alter 27 to 21 with 22 age 22 age 25 2 24 ( 25 2 25 2 26 ) 27 to 28 provide 28 provide 30 data 28 provide 31 for 28 provide 47 within 29 normative 30 data 31 for 40 and 32 upper 33 and 33 and 36 depths 33 and 38 fds 33 and 40 and 34 lower 35 fornix 35 fornix 36 depths 37 ( 38 fds 38 fds 39 ) 40 and 43 distance 40 and 45 ficd 41 fornix 43 distance 42 intercanthal 43 distance 44 ( 45 ficd 45 ficd 46 ) 47 within 51 asian 48 a 49 healthy 48 a 51 asian 49 healthy 51 asian 50 south 51 asian 51 asian 55 population 52 , 55 population 53 racially 54 distinct 54 distinct 55 population 55 population 56 . design : epidemiologic , cross - sectional study . 0 ###LEFT-WALL### 1 design 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 4 , 0 ###LEFT-WALL### 9 . 1 design 2 : 2 : 3 epidemiologic 4 , 5 cross 4 , 6 - 6 - 8 study 7 sectional 8 study participants : a total of 240 subjects with national origins from south asia , with no known ocular history and normal adnexal and conjunctival examination , aged 20 to 80 years . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 2 : 1 participants 2 : 2 : 4 total 3 a 4 total 4 total 5 of 4 total 8 with 5 of 7 subjects 6 240 7 subjects 8 with 10 origins 9 national 10 origins 10 origins 11 from 11 from 13 asia 12 south 13 asia 13 asia 15 with 13 asia 27 aged 14 , 15 with 15 with 20 and 15 with 26 , 16 no 17 known 17 known 19 history 18 ocular 19 history 19 history 20 and 20 and 25 examination 21 normal 25 examination 22 adnexal 23 and 23 and 24 conjunctival 23 and 25 examination 26 , 27 aged 27 aged 28 20 27 aged 29 to 27 aged 32 . 29 to 31 years 30 80 31 years methods : an ficd modification of a custom - designed fornix depth measurer ( fdm ) was validated and used for measurement of both [lower] and upper fds together with ficds in 480 healthy eyes with no ocular comorbidities . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 4 ficd 3 an 4 ficd 4 ficd 5 modification 4 ficd 19 and 5 modification 6 of 5 modification 13 measurer 5 modification 17 was 6 of 8 custom 7 a 8 custom 9 - 13 measurer 10 designed 13 measurer 11 fornix 12 depth 12 depth 13 measurer 13 measurer 15 fdm 13 measurer 16 ) 14 ( 15 fdm 15 fdm 16 ) 17 was 19 and 18 validated 19 and 19 and 20 used 19 and 21 for 21 for 26 and 22 measurement 23 of 22 measurement 26 and 23 of 24 both 26 and 28 fds 26 and 40 . 27 upper 28 fds 28 fds 30 with 29 together 30 with 30 with 31 ficds 31 ficds 32 in 31 ficds 36 with 32 in 35 eyes 33 480 35 eyes 34 healthy 35 eyes 36 with 39 comorbidities 37 no 39 comorbidities 38 ocular 39 comorbidities data were analyzed using repeated - measures analysis of variance and presented as means with 95 % confidence intervals ( cis ) . 0 ###LEFT-WALL### 1 data 0 ###LEFT-WALL### 2 were 0 ###LEFT-WALL### 6 - 0 ###LEFT-WALL### 23 . 1 data 2 were 2 were 4 using 3 analyzed 4 using 4 using 5 repeated 6 - 11 and 7 measures 8 analysis 7 measures 11 and 8 analysis 9 of 9 of 10 variance 11 and 12 presented 12 presented 13 as 12 presented 15 with 12 presented 19 intervals 13 as 14 means 15 with 17 % 16 95 17 % 18 confidence 19 intervals 19 intervals 21 cis 20 ( 21 cis 21 cis 22 ) main outcome measures : mean lower and upper fds and ficd for the entire cohort , stratified according to age [decade] and sex . 0 ###LEFT-WALL### 3 measures 0 ###LEFT-WALL### 4 : 0 ###LEFT-WALL### 16 , 0 ###LEFT-WALL### 24 . 1 main 2 outcome 2 outcome 3 measures 3 measures 4 : 4 : 11 ficd 4 : 12 for 5 mean 6 lower 5 mean 7 and 7 and 8 upper 7 and 11 ficd 9 fds 10 and 10 and 11 ficd 12 for 15 cohort 13 the 15 cohort 14 entire 15 cohort 16 , 22 and 17 stratified 19 to 17 stratified 22 and 18 according 19 to 19 to 20 age 22 and 23 sex with increasing age , a progressive reduction of all measured parameters ( p < 0.001 ) was noted [,] with female subjects having significantly shallower fornices ( upper fd , p < 0.001 [;] lower fd , p < 0.001 [;] upper ficd , p = 0.081 [;] and lower ficd , p = 0.015 [ )( 1 with 2 increasing 1 with 4 , 1 with 7 reduction 2 increasing 3 age 5 a 7 reduction 6 progressive 7 reduction 7 reduction 8 of 7 reduction 17 was 8 of 11 parameters 9 all 11 parameters 10 measured 11 parameters 11 parameters 14 < 12 ( 14 < 13 p 14 < 14 < 15 0.001 14 < 16 ) 17 was 18 noted 18 noted 20 with 20 with 22 subjects 20 with 23 having 21 female 22 subjects 23 having 26 fornices 23 having 32 < 23 having 35 lower 24 significantly 25 shallower 25 shallower 26 fornices 26 fornices 29 fd 27 ( 29 fd 28 upper 29 fd 29 fd 30 , 31 p 32 < 32 < 33 0.001 35 lower 36 fd 35 lower 39 < 37 , 39 < 38 p 39 < 39 < 51 ficd 40 0.001 51 ficd 42 upper 51 ficd 43 ficd 46 = 43 ficd 49 and 44 , 46 = 45 p 46 = 46 = 47 0.081 49 and 50 lower 49 and 51 ficd 51 ficd 54 = 52 , 54 = 53 p 54 = 54 = 55 0.015 54 = 57 )( conclusions : this is the first study to define the limits of normal upper fd and ficds in any population group . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 22 . 2 : 3 this 2 : 4 is 3 this 4 is 4 is 7 study 4 is 8 to 4 is 18 in 5 the 7 study 6 first 7 study 8 to 9 define 9 define 16 and 10 the 11 limits 11 limits 12 of 11 limits 16 and 12 of 15 fd 13 normal 15 fd 14 upper 15 fd 16 and 17 ficds 18 in 21 group 19 any 21 group 20 population 21 group our study demonstrates sex variations and progressive conjunctival shrinkage with age . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 demonstrates 0 ###LEFT-WALL### 12 . 1 our 2 study 2 study 3 demonstrates 3 demonstrates 6 and 3 demonstrates 10 with 4 sex 5 variations 5 variations 6 and 6 and 9 shrinkage 7 progressive 9 shrinkage 8 conjunctival 9 shrinkage 10 with 11 age although it provides important , objective data for normal forniceal anatomy , further study is recommended in other populations to confirm the generalizability of these data or to enable normal comparative datasets for the assessment of conjunctival scarring disorders among all anthropological groups . 0 ###LEFT-WALL### 14 study 0 ###LEFT-WALL### 27 or 0 ###LEFT-WALL### 44 . 1 although 2 it 1 although 3 provides 1 although 14 study 2 it 3 provides 4 important 7 data 4 important 14 study 5 , 7 data 6 objective 7 data 7 data 8 for 7 data 12 , 8 for 11 anatomy 9 normal 11 anatomy 10 forniceal 11 anatomy 13 further 14 study 14 study 15 is 15 is 16 recommended 16 recommended 17 in 16 recommended 20 to 17 in 19 populations 18 other 19 populations 20 to 27 or 21 confirm 23 generalizability 21 confirm 27 or 22 the 23 generalizability 23 generalizability 24 of 24 of 26 data 25 these 26 data 27 or 28 to 27 or 29 enable 27 or 33 for 27 or 40 among 28 to 29 enable 29 enable 32 datasets 30 normal 32 datasets 31 comparative 32 datasets 33 for 35 assessment 34 the 35 assessment 35 assessment 36 of 36 of 39 disorders 37 conjunctival 39 disorders 38 scarring 39 disorders 40 among 43 groups 41 all 43 groups 42 anthropological 43 groups this article describes the two - process model [of] sleep regulation . 0 ###LEFT-WALL### 2 article 0 ###LEFT-WALL### 3 describes 0 ###LEFT-WALL### 6 - 1 this 2 article 2 article 3 describes 3 describes 5 two 4 the 5 two 6 - 7 process 6 - 12 . 7 process 11 regulation 8 model 11 regulation 10 sleep 11 regulation the 24 [-] hour sleep [-] wake cycle is regulated by a homeostatic process and an endogenous , 2 oscillators , circadian process , under the influence of external synchronisers . 0 ###LEFT-WALL### 8 cycle 0 ###LEFT-WALL### 10 regulated 1 the 8 cycle 2 24 4 hour 4 hour 8 cycle 5 sleep 8 cycle 7 wake 8 cycle 8 cycle 9 is 9 is 10 regulated 10 regulated 11 by 10 regulated 25 under 11 by 15 and 12 a 14 process 13 homeostatic 14 process 14 process 15 and 15 and 23 process 16 an 17 endogenous 16 an 23 process 17 endogenous 20 oscillators 17 endogenous 21 , 17 endogenous 23 process 18 , 20 oscillators 19 2 20 oscillators 20 oscillators 21 , 22 circadian 23 process 24 , 25 under 25 under 27 influence 25 under 31 . 26 the 27 influence 27 influence 28 of 28 of 30 synchronisers 29 external 30 synchronisers these two processes are partially independent but influence each other , [as] shown in the two - sleep - process auto - regulation model . 0 ###LEFT-WALL### 2 two 0 ###LEFT-WALL### 8 influence 0 ###LEFT-WALL### 19 - 1 these 2 two 2 two 3 processes 2 two 7 but 2 two 8 influence 3 processes 4 are 4 are 5 partially 4 are 6 independent 6 independent 7 but 8 influence 10 other 8 influence 13 shown 9 each 10 other 11 , 13 shown 13 shown 14 in 13 shown 19 - 14 in 16 two 15 the 16 two 16 two 18 sleep 17 - 18 sleep 18 sleep 19 - 19 - 21 auto 19 - 22 - 20 process 21 auto 22 - 24 model 22 - 25 . 23 regulation 24 model a reciprocal inhibition model of two interconnected neuronal groups , " sp [on] ["] and " sp [off] ["] , explains the regular recurrence of paradoxical sleep . 0 ###LEFT-WALL### 4 model 0 ###LEFT-WALL### 21 explains 0 ###LEFT-WALL### 28 . 1 a 2 reciprocal 1 a 4 model 2 reciprocal 3 inhibition 3 inhibition 4 model 4 model 5 of 4 model 21 explains 5 of 9 groups 6 two 9 groups 7 interconnected 9 groups 8 neuronal 9 groups 9 groups 15 and 10 , 11 " 10 , 15 and 12 sp 15 and 15 and 16 " 15 and 17 sp 15 and 20 , 21 explains 24 recurrence 22 the 24 recurrence 23 regular 24 recurrence 24 recurrence 25 of 25 of 27 sleep 26 paradoxical 27 sleep sleep studies have primarily depended on observation of the subject and have determined the optimal conditions for sleep ( position , external conditions , sleep duration and need ) and have studied the consequences of sleep deprivation or modifications of sleep schedules . 0 ###LEFT-WALL### 38 or 0 ###LEFT-WALL### 43 . 1 sleep 2 studies 2 studies 11 and 2 studies 38 or 3 have 5 depended 3 have 11 and 4 primarily 5 depended 5 depended 6 on 6 on 7 observation 7 observation 8 of 8 of 10 subject 9 the 10 subject 11 and 30 and 12 have 13 determined 12 have 30 and 13 determined 16 conditions 14 the 16 conditions 15 optimal 16 conditions 16 conditions 17 for 16 conditions 27 and 17 for 18 sleep 19 ( 27 and 20 position 21 , 21 , 23 conditions 21 , 24 , 22 external 23 conditions 24 , 26 duration 24 , 27 and 25 sleep 26 duration 27 and 28 need 27 and 29 ) 30 and 31 have 30 and 37 deprivation 31 have 32 studied 32 studied 34 consequences 33 the 34 consequences 34 consequences 35 of 35 of 36 sleep 38 or 39 modifications 38 or 40 of 40 of 42 schedules 41 sleep 42 schedules then , electrophysiological recordings permitted the classification of sleep stages according to the observed eeg patterns . 0 ###LEFT-WALL### 4 recordings 0 ###LEFT-WALL### 5 permitted 0 ###LEFT-WALL### 17 . 1 then 2 , 1 then 4 recordings 3 electrophysiological 4 recordings 4 recordings 5 permitted 5 permitted 7 classification 5 permitted 12 to 6 the 7 classification 7 classification 8 of 8 of 10 stages 9 sleep 10 stages 11 according 12 to 12 to 16 patterns 13 the 16 patterns 14 observed 16 patterns 15 eeg 16 patterns the course of a night 's sleep is reported on a " hypnogram " . 0 ###LEFT-WALL### 2 course 0 ###LEFT-WALL### 9 reported 0 ###LEFT-WALL### 15 . 1 the 2 course 2 course 3 of 2 course 8 is 3 of 7 sleep 4 a 5 night 5 night 6 's 6 's 7 sleep 8 is 9 reported 9 reported 10 on 10 on 13 hypnogram 11 a 12 " 11 a 13 hypnogram 13 hypnogram 14 " the adult subject falls asleep in [non] [-] rem sleep ( n1 ) , then sleep deepens progressively to stages n2 and n3 with the appearance of spindles and slow waves ( n2 ) . 0 ###LEFT-WALL### 3 subject 0 ###LEFT-WALL### 4 falls 0 ###LEFT-WALL### 15 then 0 ###LEFT-WALL### 35 . 1 the 3 subject 2 adult 3 subject 3 subject 4 falls 4 falls 5 asleep 4 falls 6 in 4 falls 15 then 6 in 10 sleep 9 rem 10 sleep 10 sleep 12 n1 11 ( 12 n1 12 n1 13 ) 14 , 15 then 15 then 16 sleep 15 then 29 and 16 sleep 17 deepens 17 deepens 18 progressively 17 deepens 19 to 19 to 29 and 20 stages 23 n3 20 stages 24 with 20 stages 29 and 21 n2 22 and 22 and 23 n3 24 with 26 appearance 25 the 26 appearance 26 appearance 27 of 27 of 28 spindles 29 and 30 slow 30 slow 31 waves 31 waves 33 n2 32 ( 33 n2 33 n2 34 ) slow waves become more numerous in stage n3 . 0 ###LEFT-WALL### 1 slow 0 ###LEFT-WALL### 9 . 1 slow 2 waves 2 waves 3 become 2 waves 5 numerous 4 more 5 numerous 5 numerous 6 in 6 in 8 n3 7 stage 8 n3 every 90 minutes rem sleep recurs , with muscle atonia and rapid eye movements . 0 ###LEFT-WALL### 5 sleep 0 ###LEFT-WALL### 6 recurs 1 every 2 90 2 90 3 minutes 3 minutes 5 sleep 4 rem 5 sleep 5 sleep 6 recurs 6 recurs 8 with 7 , 8 with 8 with 14 movements 8 with 15 . 9 muscle 14 movements 10 atonia 11 and 11 and 12 rapid 11 and 13 eye 13 eye 14 movements these adult sleep patterns develop progressively during the 2 first years of life as total sleep duration decreases , with the reduction of diurnal sleep and [of] rem sleep . 0 ###LEFT-WALL### 4 patterns 0 ###LEFT-WALL### 5 develop 0 ###LEFT-WALL### 19 , 0 ###LEFT-WALL### 30 . 1 these 4 patterns 2 adult 3 sleep 3 sleep 4 patterns 4 patterns 5 develop 5 develop 6 progressively 5 develop 7 during 7 during 11 years 8 the 9 2 9 2 11 years 10 first 11 years 11 years 17 duration 11 years 18 decreases 12 of 13 life 12 of 17 duration 14 as 16 sleep 14 as 17 duration 15 total 16 sleep 17 duration 18 decreases 19 , 29 sleep 20 with 26 and 20 with 29 sleep 21 the 22 reduction 22 reduction 23 of 22 reduction 26 and 23 of 25 sleep 24 diurnal 25 sleep 26 and 28 rem around 2 to 4 months , spindles and k complexes appear on the eeg , with the differentiation of light and deep sleep [with] , however , a predominance of slow wave sleep . 0 ###LEFT-WALL### 10 complexes 0 ###LEFT-WALL### 11 appear 1 around 8 and 1 around 10 complexes 2 2 3 to 3 to 4 4 3 to 5 months 5 months 6 , 6 , 7 spindles 6 , 8 and 8 and 9 k 10 complexes 11 appear 11 appear 12 on 12 on 14 eeg 13 the 14 eeg 14 eeg 16 with 15 , 16 with 16 with 21 and 16 with 26 however 16 with 29 predominance 16 with 34 . 17 the 18 differentiation 18 differentiation 19 of 18 differentiation 21 and 19 of 20 light 21 and 23 sleep 22 deep 23 sleep 25 , 26 however 26 however 27 , 28 a 29 predominance 29 predominance 30 of 30 of 33 sleep 31 slow 32 wave 32 wave 33 sleep parkinson disease ( pd ) is common in long term care ( ltc ) [facilities] . 0 ###LEFT-WALL### 2 disease 0 ###LEFT-WALL### 6 is 0 ###LEFT-WALL### 16 . 1 parkinson 2 disease 2 disease 4 pd 2 disease 6 is 3 ( 4 pd 4 pd 5 ) 6 is 7 common 7 common 8 in 8 in 11 care 9 long 10 term 10 term 11 care 11 care 13 ltc 12 ( 13 ltc 13 ltc 14 ) the number of institutionalized patients with pd will rise sharply in the coming decades because of 2 concurrent phenomena : aging of the population leads to an increased pd prevalence and improved quality of care has led to a prolonged survival in advanced disease stages . 0 ###LEFT-WALL### 5 patients 0 ###LEFT-WALL### 9 rise 0 ###LEFT-WALL### 20 : 1 the 2 number 2 number 3 of 2 number 5 patients 3 of 5 patients 4 institutionalized 5 patients 5 patients 6 with 5 patients 8 will 6 with 7 pd 8 will 9 rise 9 rise 10 sharply 9 rise 11 in 9 rise 15 because 11 in 14 decades 12 the 14 decades 13 coming 14 decades 15 because 16 of 16 of 19 phenomena 17 2 19 phenomena 18 concurrent 19 phenomena 20 : 21 aging 20 : 37 led 20 : 46 . 21 aging 22 of 21 aging 31 and 21 aging 33 quality 21 aging 36 has 21 aging 37 led 22 of 24 population 23 the 24 population 25 leads 26 to 25 leads 31 and 26 to 30 prevalence 27 an 30 prevalence 28 increased 30 prevalence 29 pd 30 prevalence 31 and 32 improved 33 quality 34 of 33 quality 36 has 34 of 35 care 37 led 38 to 38 to 41 survival 39 a 41 survival 40 prolonged 41 survival 41 survival 42 in 42 in 45 stages 43 advanced 44 disease 44 disease 45 stages only a few studies have investigated the prevalence and clinical characteristics of patients with pd in ltc facilities . 0 ###LEFT-WALL### 4 studies 0 ###LEFT-WALL### 6 investigated 0 ###LEFT-WALL### 19 . 1 only 3 few 2 a 3 few 3 few 4 studies 4 studies 5 have 5 have 6 investigated 6 investigated 18 facilities 7 the 8 prevalence 8 prevalence 9 and 9 and 11 characteristics 9 and 12 of 9 and 18 facilities 10 clinical 11 characteristics 12 of 13 patients 13 patients 14 with 13 patients 16 in 14 with 15 pd 16 in 17 ltc even fewer studies have addressed the treatment strategies used to support these institutionalized patients , who are mostly in advanced stages of the disease . 0 ###LEFT-WALL### 3 studies 0 ###LEFT-WALL### 5 addressed 0 ###LEFT-WALL### 15 , 0 ###LEFT-WALL### 25 . 1 even 2 fewer 2 fewer 3 studies 3 studies 4 have 4 have 5 addressed 5 addressed 8 strategies 5 addressed 10 to 6 the 8 strategies 7 treatment 8 strategies 8 strategies 9 used 10 to 11 support 11 support 14 patients 12 these 14 patients 13 institutionalized 14 patients 15 , 16 who 15 , 17 are 16 who 17 are 17 are 18 mostly 17 are 19 in 19 in 21 stages 20 advanced 21 stages 21 stages 22 of 22 of 24 disease 23 the 24 disease the available evidence suggests that current management of patients with pd in ltc facilities is less than optimal . 0 ###LEFT-WALL### 3 evidence 0 ###LEFT-WALL### 4 suggests 0 ###LEFT-WALL### 19 . 1 the 3 evidence 2 available 3 evidence 3 evidence 4 suggests 4 suggests 5 that 5 that 7 management 5 that 17 than 6 current 7 management 7 management 8 of 7 management 10 with 7 management 17 than 8 of 9 patients 10 with 11 pd 11 pd 12 in 12 in 14 facilities 13 ltc 14 facilities 15 is 16 less 16 less 17 than 17 than 18 optimal in the netherlands , and we suspect in many other countries , there are no formal guidelines for treating patients with pd who have been admitted to a ltc facility . 0 ###LEFT-WALL### 7 suspect 0 ###LEFT-WALL### 31 . 1 in 5 and 1 in 7 suspect 2 the 3 netherlands 3 netherlands 5 and 4 , 5 and 5 and 6 we 7 suspect 13 there 7 suspect 14 are 8 in 11 countries 8 in 12 , 8 in 13 there 9 many 10 other 10 other 11 countries 13 there 14 are 14 are 17 guidelines 14 are 21 with 15 no 17 guidelines 16 formal 17 guidelines 17 guidelines 18 for 18 for 19 treating 19 treating 20 patients 21 with 22 pd 22 pd 23 who 22 pd 24 have 23 who 24 have 24 have 25 been 25 been 26 admitted 26 admitted 27 to 27 to 30 facility 28 a 30 facility 29 ltc 30 facility in this review , we describe the epidemiology , clinical characteristics , and clinical management of patients with pd in ltc settings . 0 ###LEFT-WALL### 5 we 0 ###LEFT-WALL### 6 describe 0 ###LEFT-WALL### 23 . 1 in 3 review 1 in 4 , 1 in 5 we 2 this 3 review 5 we 6 describe 6 describe 13 and 6 describe 18 with 6 describe 20 in 7 the 8 epidemiology 8 epidemiology 9 , 9 , 11 characteristics 9 , 13 and 10 clinical 11 characteristics 12 , 13 and 13 and 15 management 13 and 16 of 14 clinical 15 management 16 of 17 patients 18 with 19 pd 20 in 22 settings 21 ltc 22 settings we also address potentially modifiable elements of care and provide several recommendations to improve the management of pd in these facilities . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 22 . 1 we 9 and 2 also 3 address 3 address 6 elements 3 address 9 and 4 potentially 5 modifiable 5 modifiable 6 elements 6 elements 7 of 7 of 8 care 9 and 10 provide 10 provide 12 recommendations 10 provide 13 to 11 several 12 recommendations 13 to 14 improve 14 improve 16 management 14 improve 19 in 15 the 16 management 16 management 17 of 17 of 18 pd 19 in 21 facilities 20 these 21 facilities we conclude by suggesting a possible guide for future research in this area . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 conclude 0 ###LEFT-WALL### 14 . 1 we 2 conclude 2 conclude 3 by 2 conclude 13 area 3 by 4 suggesting 4 suggesting 7 guide 4 suggesting 11 in 5 a 6 possible 5 a 7 guide 6 possible 7 guide 7 guide 8 for 8 for 10 research 9 future 10 research 11 in 12 this objective : this study aimed to examine the cross - sectional and longitudinal relationships between physical frailty at baseline and depressive symptoms at baseline and at [follow] - up . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 2 : 4 study 2 : 5 aimed 3 this 4 study 4 study 5 aimed 5 aimed 6 to 5 aimed 7 examine 6 to 7 examine 7 examine 9 cross 8 the 9 cross 9 cross 20 and 10 - 20 and 11 sectional 12 and 12 and 13 longitudinal 12 and 14 relationships 14 relationships 15 between 14 relationships 20 and 15 between 17 frailty 16 physical 17 frailty 17 frailty 18 at 18 at 19 baseline 20 and 22 symptoms 20 and 25 and 20 and 30 . 21 depressive 22 symptoms 23 at 24 baseline 23 at 25 and 25 and 26 at 26 at 29 up 28 - 29 up design : four - year prospective study . 0 ###LEFT-WALL### 1 design 0 ###LEFT-WALL### 2 : 2 : 3 four 2 : 4 - 2 : 8 . 4 - 7 study 5 year 7 study 6 prospective 7 study setting : communities in the south east region of singapore . 0 ###LEFT-WALL### 1 setting 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 11 . 1 setting 2 : 2 : 3 communities 3 communities 4 in 4 in 8 region 5 the 8 region 6 south 7 east 7 east 8 region 8 region 9 of 9 of 10 singapore participants : we analyzed data of 1827 older chinese adults aged 55 [and] above in the singapore longitudinal aging study [-] i . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 23 . 2 : 3 we 2 : 4 analyzed 3 we 4 analyzed 4 analyzed 5 data 4 analyzed 14 above 4 analyzed 15 in 5 data 6 of 6 of 10 adults 7 1827 10 adults 8 older 10 adults 9 chinese 10 adults 10 adults 11 aged 11 aged 12 55 15 in 20 study 16 the 20 study 17 singapore 18 longitudinal 18 longitudinal 19 aging 19 aging 20 study 20 study 22 i measurements : the frailty phenotype ( based on fried criteria ) was determined at baseline , depressive symptoms ( geriatric depression scale ≥ 5 ) at baseline and [follow] [-] ups at 2 and 4 years . 0 ###LEFT-WALL### 1 measurements 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 37 . 2 : 5 phenotype 2 : 28 and 3 the 5 phenotype 4 frailty 5 phenotype 5 phenotype 7 based 5 phenotype 28 and 6 ( 7 based 7 based 8 on 7 based 11 ) 8 on 10 criteria 9 fried 10 criteria 12 was 13 determined 12 was 28 and 13 determined 14 at 13 determined 26 at 14 at 15 baseline 15 baseline 18 symptoms 16 , 18 symptoms 17 depressive 18 symptoms 18 symptoms 23 ≥ 18 symptoms 25 ) 19 ( 23 ≥ 20 geriatric 21 depression 21 depression 22 scale 22 scale 23 ≥ 23 ≥ 24 5 23 ≥ 25 ) 26 at 27 baseline 28 and 31 ups 28 and 32 at 28 and 36 years 32 at 34 and 33 2 34 and 34 and 35 4 results : the mean age of the population was 65.9 ( standard deviation 7.26 ) . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 5 age 2 : 9 was 2 : 16 . 3 the 5 age 4 mean 5 age 5 age 6 of 5 age 9 was 6 of 8 population 7 the 8 population 9 was 10 65.9 10 65.9 13 deviation 11 ( 13 deviation 12 standard 13 deviation 13 deviation 14 7.26 13 deviation 15 ) at baseline , 11.4 % ( n = 209 ) had depressive symptoms , 32.4 % ( n = 591 ) were prefrail and 2.5 % ( n = 46 ) were frail . 0 ###LEFT-WALL### 5 % 0 ###LEFT-WALL### 11 had 0 ###LEFT-WALL### 14 , 0 ###LEFT-WALL### 34 . 1 at 2 baseline 1 at 3 , 1 at 5 % 4 11.4 5 % 5 % 8 = 5 % 11 had 6 ( 8 = 7 n 8 = 8 = 9 209 8 = 10 ) 11 had 13 symptoms 12 depressive 13 symptoms 14 , 26 % 14 , 32 were 15 32.4 16 % 15 32.4 24 and 16 % 19 = 16 % 22 were 17 ( 19 = 18 n 19 = 19 = 20 591 19 = 21 ) 22 were 23 prefrail 24 and 25 2.5 24 and 26 % 26 % 29 = 26 % 32 were 27 ( 29 = 28 n 29 = 29 = 30 46 29 = 31 ) 32 were 33 frail in cross - sectional analysis of baseline data , the adjusted odds ratios [(] or )s and 95 % confidence intervals controlling for demographic , comorbidities , and other confounders were 1.69 ( 1.23 - 2.33 ) for prefrailty and 2.36 ( 1.08 - 5.15 ) [for] frailty , ( [p] for linear trend [<] [.] 001 [ )( 0 ###LEFT-WALL### 2 cross 0 ###LEFT-WALL### 3 - 1 in 2 cross 3 - 5 analysis 3 - 9 , 4 sectional 5 analysis 5 analysis 6 of 6 of 8 data 7 baseline 8 data 9 , 15 or 9 , 16 )s 9 , 17 and 10 the 15 or 11 adjusted 12 odds 12 odds 13 ratios 13 ratios 15 or 15 or 16 )s 17 and 21 intervals 18 95 21 intervals 19 % 21 intervals 20 confidence 21 intervals 21 intervals 22 controlling 21 intervals 31 were 22 controlling 23 for 22 controlling 30 confounders 23 for 28 and 24 demographic 25 , 24 demographic 26 comorbidities 26 comorbidities 28 and 27 , 28 and 28 and 29 other 31 were 32 1.69 31 were 38 for 32 1.69 35 - 33 ( 35 - 34 1.23 35 - 35 - 36 2.33 35 - 37 ) 38 for 40 and 39 prefrailty 40 and 40 and 48 frailty 40 and 49 , 40 and 52 for 41 2.36 48 frailty 42 ( 44 - 43 1.08 44 - 44 - 45 5.15 44 - 46 ) 44 - 48 frailty 50 ( 52 for 52 for 54 trend 52 for 59 )( 53 linear 54 trend 54 trend 57 001 in longitudinal data analyses , prospective associations among all participants were : prefrail : or = 1.86 ( 1.08 - 3.20 ) ; [frail] : or = 3.09 ( 1.12 - 8.50 ) [;] ( [p] for linear trend [=] [.] 009 ) . 0 ###LEFT-WALL### 7 associations 0 ###LEFT-WALL### 11 were 0 ###LEFT-WALL### 12 : 0 ###LEFT-WALL### 27 = 0 ###LEFT-WALL### 44 . 1 in 4 analyses 1 in 5 , 1 in 7 associations 2 longitudinal 3 data 3 data 4 analyses 6 prospective 7 associations 7 associations 8 among 7 associations 11 were 8 among 10 participants 9 all 10 participants 12 : 13 prefrail 12 : 14 : 14 : 15 or 14 : 16 = 14 : 23 ; 15 or 16 = 16 = 17 1.86 17 1.86 20 - 18 ( 20 - 19 1.08 20 - 20 - 21 3.20 20 - 22 ) 23 ; 25 : 25 : 26 or 26 or 27 = 27 = 28 3.09 27 = 31 - 27 = 37 for 29 ( 31 - 30 1.12 31 - 31 - 32 8.50 31 - 33 ) 35 ( 37 for 37 for 39 trend 37 for 43 ) 38 linear 39 trend 39 trend 42 009 among participants free of depressive symptoms at baseline , similar prospective associations were found : prefrail or = 2.26 ( 1.12 - 4.57 ) ; [frail] : or = 3.75 ( 1.07 - 13.16 ) [;] ( [p] for linear trend [=] [.] 009 ) . 0 ###LEFT-WALL### 12 associations 0 ###LEFT-WALL### 14 found 0 ###LEFT-WALL### 15 : 0 ###LEFT-WALL### 46 . 1 among 2 participants 1 among 9 , 1 among 12 associations 2 participants 3 free 3 free 4 of 3 free 7 at 4 of 6 symptoms 5 depressive 6 symptoms 7 at 8 baseline 10 similar 12 associations 11 prospective 12 associations 12 associations 13 were 13 were 14 found 15 : 17 or 15 : 18 = 15 : 25 ; 16 prefrail 17 or 17 or 18 = 18 = 19 2.26 18 = 22 - 20 ( 22 - 21 1.12 22 - 22 - 23 4.57 22 - 24 ) 25 ; 27 : 25 ; 29 = 27 : 28 or 28 or 29 = 29 = 30 3.75 29 = 33 - 29 = 39 for 31 ( 33 - 32 1.07 33 - 33 - 34 13.16 33 - 35 ) 37 ( 39 for 39 for 41 trend 39 for 45 ) 40 linear 41 trend 41 trend 44 009 conclusion : these data support a significant role of frailty as a predictor of depression in a relatively younger old chinese population . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 4 data 2 : 5 support 2 : 23 . 3 these 4 data 4 data 5 support 5 support 8 role 5 support 11 as 5 support 16 in 6 a 7 significant 6 a 8 role 7 significant 8 role 8 role 9 of 9 of 10 frailty 11 as 13 predictor 12 a 13 predictor 13 predictor 14 of 14 of 15 depression 16 in 22 population 17 a 18 relatively 17 a 22 population 18 relatively 19 younger 19 younger 22 population 20 old 22 population 21 chinese 22 population further observational and interventional studies should explore short - term dynamic and bidirectional associations and the effects of frailty reversal on depression risk . 0 ###LEFT-WALL### 5 studies 0 ###LEFT-WALL### 7 explore 0 ###LEFT-WALL### 9 - 1 further 5 studies 2 observational 3 and 3 and 4 interventional 3 and 5 studies 5 studies 6 should 6 should 7 explore 7 explore 8 short 9 - 10 term 9 - 24 . 10 term 14 associations 10 term 15 and 10 term 21 on 11 dynamic 12 and 12 and 13 bidirectional 12 and 14 associations 15 and 17 effects 16 the 17 effects 17 effects 18 of 18 of 20 reversal 19 frailty 20 reversal 21 on 23 risk 22 depression 23 risk background : cancer survival is a key measure of the effectiveness of health - care systems . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 4 survival 2 : 5 is 2 : 14 - 3 cancer 4 survival 4 survival 5 is 5 is 8 measure 6 a 8 measure 7 key 8 measure 8 measure 9 of 9 of 11 effectiveness 10 the 11 effectiveness 11 effectiveness 12 of 12 of 13 health 14 - 16 systems 14 - 17 . 15 care 16 systems eurocare - the largest cooperative study of population - based cancer survival in europe - has shown persistent differences between countries for cancer survival , although in general , cancer survival is improving . 0 ###LEFT-WALL### 1 eurocare 0 ###LEFT-WALL### 32 is 0 ###LEFT-WALL### 34 . 1 eurocare 6 study 1 eurocare 16 has 2 - 6 study 3 the 4 largest 3 the 6 study 5 cooperative 6 study 6 study 7 of 6 study 12 survival 6 study 15 - 7 of 8 population 9 - 12 survival 10 based 11 cancer 11 cancer 12 survival 12 survival 13 in 12 survival 15 - 13 in 14 europe 16 has 17 shown 17 shown 19 differences 17 shown 24 survival 17 shown 26 although 18 persistent 19 differences 19 differences 20 between 19 differences 22 for 20 between 21 countries 22 for 23 cancer 25 , 26 although 26 although 31 survival 27 in 30 cancer 27 in 31 survival 28 general 29 , 28 general 30 cancer 31 survival 32 is 32 is 33 improving major changes in cancer diagnosis , treatment , and rehabilitation occurred in the early 2000s . 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 11 occurred 0 ###LEFT-WALL### 16 . 1 major 2 changes 2 changes 3 in 2 changes 9 and 3 in 5 diagnosis 4 cancer 5 diagnosis 5 diagnosis 7 treatment 6 , 7 treatment 7 treatment 8 , 8 , 9 and 9 and 10 rehabilitation 9 and 11 occurred 11 occurred 12 in 12 in 15 2000s 13 the 15 2000s 14 early 15 2000s eurocare [-] 5 assesses their effect on cancer survival in 29 european countries . 0 ###LEFT-WALL### 1 eurocare 0 ###LEFT-WALL### 4 assesses 0 ###LEFT-WALL### 14 . 1 eurocare 3 5 1 eurocare 4 assesses 4 assesses 6 effect 4 assesses 7 on 4 assesses 10 in 5 their 6 effect 7 on 9 survival 8 cancer 9 survival 10 in 13 countries 11 29 13 countries 12 european 13 countries methods : in this retrospective observational study , we analysed data from 107 cancer registries for more than 10 million patients with cancer diagnosed up to 2007 and followed up to 2008 . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 8 , 0 ###LEFT-WALL### 33 . 1 methods 2 : 2 : 3 in 3 in 7 study 4 this 5 retrospective 5 retrospective 7 study 6 observational 7 study 8 , 9 we 8 , 28 and 9 we 28 and 10 analysed 11 data 10 analysed 24 diagnosed 10 analysed 28 and 11 data 12 from 11 data 24 diagnosed 12 from 15 registries 13 107 15 registries 14 cancer 15 registries 15 registries 16 for 15 registries 22 with 16 for 21 patients 17 more 18 than 18 than 20 million 19 10 20 million 20 million 21 patients 22 with 23 cancer 24 diagnosed 27 2007 25 up 26 to 26 to 27 2007 28 and 29 followed 28 and 30 up 28 and 31 to 31 to 32 2008 uniform quality control procedures were applied to all datasets . 0 ###LEFT-WALL### 4 procedures 0 ###LEFT-WALL### 6 applied 0 ###LEFT-WALL### 10 . 1 uniform 2 quality 2 quality 4 procedures 3 control 4 procedures 4 procedures 5 were 5 were 6 applied 6 applied 7 to 7 to 9 datasets 8 all 9 datasets for patients diagnosed 2000 - 07 , we calculated 5 - year relative survival for 46 cancers weighted by age and country . 0 ###LEFT-WALL### 8 we 0 ###LEFT-WALL### 9 calculated 0 ###LEFT-WALL### 11 - 0 ###LEFT-WALL### 23 . 1 for 2 patients 1 for 8 we 3 diagnosed 5 - 3 diagnosed 7 , 3 diagnosed 8 we 4 2000 5 - 5 - 6 07 8 we 9 calculated 9 calculated 10 5 11 - 21 and 12 year 14 survival 13 relative 14 survival 14 survival 15 for 14 survival 21 and 15 for 17 cancers 16 46 17 cancers 17 cancers 18 weighted 18 weighted 19 by 19 by 20 age 21 and 22 country [we] also calculated country - specific and age - specific survival for ten common cancers , together with survival differences between time periods ( for 1999 - 2001 , 2002 - 04 , [and] 2005 - 07 ) . 0 ###LEFT-WALL### 4 country 0 ###LEFT-WALL### 5 - 2 also 3 calculated 3 calculated 4 country 5 - 7 and 5 - 39 . 6 specific 7 and 7 and 8 age 7 and 11 survival 9 - 11 survival 10 specific 11 survival 11 survival 12 for 11 survival 38 ) 12 for 15 cancers 13 ten 15 cancers 14 common 15 cancers 15 cancers 18 with 15 cancers 28 2001 15 cancers 31 - 16 , 18 with 17 together 18 with 18 with 20 differences 18 with 27 - 19 survival 20 differences 20 differences 21 between 21 between 23 periods 22 time 23 periods 23 periods 25 for 24 ( 25 for 25 for 26 1999 25 for 27 - 27 - 28 2001 28 2001 29 , 29 , 31 - 30 2002 31 - 31 - 32 04 31 - 36 - 31 - 38 ) 33 , 36 - 35 2005 36 - 36 - 37 07 36 - 38 ) findings : 5 - year relative survival generally increased steadily over time for all european regions . 0 ###LEFT-WALL### 1 findings 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 9 increased 0 ###LEFT-WALL### 17 . 2 : 3 5 2 : 4 - 3 5 4 - 4 - 7 survival 5 year 7 survival 6 relative 7 survival 7 survival 9 increased 8 generally 9 increased 9 increased 10 steadily 9 increased 11 over 11 over 12 time 12 time 13 for 13 for 16 regions 14 all 16 regions 15 european 16 regions the largest increases from 1999 - 2001 to 2005 - 07 were for prostate cancer ( 73.4 % [ 95 % ci 72.9 - 73.9 []] vs 81.7 % [ 81.3 - 82.1 ] ) , [non] - hodgkin [lymphoma] ( 53.8 % [ 53.3 - 54.4 ] vs 60.4 % [ 60.0 - 60.9 ] ) , and rectal cancer ( 52.1 % [ 51.6 - 52.6 []] vs 57.6 % [ 57.1 - 58.1 ] ) . 0 ###LEFT-WALL### 3 increases 0 ###LEFT-WALL### 12 were 0 ###LEFT-WALL### 38 - 0 ###LEFT-WALL### 79 . 1 the 2 largest 1 the 3 increases 3 increases 4 from 3 increases 8 to 3 increases 12 were 4 from 6 - 5 1999 6 - 6 - 7 2001 8 to 10 - 9 2005 10 - 10 - 11 07 12 were 13 for 13 for 15 cancer 14 prostate 15 cancer 15 cancer 18 % 15 cancer 25 73.9 16 ( 18 % 17 73.4 18 % 18 % 22 ci 18 % 24 - 19 [ 22 ci 20 95 22 ci 21 % 22 ci 22 ci 23 72.9 22 ci 24 - 24 - 25 73.9 25 73.9 27 vs 25 73.9 36 , 27 vs 29 % 28 81.7 29 % 29 % 31 81.3 30 [ 31 81.3 31 81.3 33 82.1 31 81.3 35 ) 32 - 33 82.1 33 82.1 34 ] 38 - 59 and 39 hodgkin 43 % 39 hodgkin 49 vs 39 hodgkin 59 and 41 ( 43 % 42 53.8 43 % 43 % 46 - 43 % 48 ] 44 [ 46 - 45 53.3 46 - 46 - 47 54.4 46 - 48 ] 49 vs 51 % 50 60.4 51 % 51 % 53 60.0 52 [ 53 60.0 53 60.0 55 60.9 53 60.0 57 ) 54 - 55 60.9 55 60.9 56 ] 58 , 59 and 59 and 61 cancer 59 and 64 % 60 rectal 61 cancer 62 ( 64 % 63 52.1 64 % 64 % 66 51.6 64 % 68 52.6 64 % 78 ) 65 [ 66 51.6 66 51.6 67 - 67 - 68 52.6 68 52.6 70 vs 68 52.6 75 - 68 52.6 77 ] 70 vs 72 % 71 57.6 72 % 73 [ 75 - 74 57.1 75 - 75 - 76 58.1 75 - 77 ] survival in eastern europe was generally low [and] below the european mean , particularly for cancers with good or intermediate prognosis . 0 ###LEFT-WALL### 1 survival 0 ###LEFT-WALL### 5 was 1 survival 2 in 1 survival 5 was 2 in 4 europe 3 eastern 4 europe 5 was 6 generally 5 was 7 low 7 low 9 below 7 low 15 for 9 below 12 mean 10 the 12 mean 11 european 12 mean 13 , 14 particularly 13 , 15 for 15 for 16 cancers 15 for 22 . 16 cancers 17 with 17 with 19 or 18 good 19 or 19 or 21 prognosis 20 intermediate 21 prognosis survival was [highest] for [northern] [,] central , and southern europe . 0 ###LEFT-WALL### 1 survival 0 ###LEFT-WALL### 2 was 0 ###LEFT-WALL### 12 . 1 survival 2 was 2 was 4 for 4 for 9 and 7 central 9 and 8 , 9 and 9 and 11 europe 10 southern 11 europe survival in the uk and ireland was intermediate for rectal cancer , breast cancer , prostate cancer , skin melanoma , and [non] [-] hodgkin lymphoma , but low [for] kidney , stomach , ovarian , colon , and lung cancers . 0 ###LEFT-WALL### 1 survival 0 ###LEFT-WALL### 7 was 0 ###LEFT-WALL### 18 , 0 ###LEFT-WALL### 42 . 1 survival 2 in 1 survival 7 was 2 in 5 and 3 the 4 uk 4 uk 5 and 5 and 6 ireland 7 was 8 intermediate 8 intermediate 9 for 9 for 11 cancer 10 rectal 11 cancer 11 cancer 14 cancer 11 cancer 17 cancer 12 , 14 cancer 13 breast 14 cancer 14 cancer 15 , 15 , 17 cancer 16 prostate 17 cancer 17 cancer 18 , 18 , 39 and 19 skin 20 melanoma 20 melanoma 22 and 21 , 22 and 22 and 31 kidney 22 and 32 , 25 hodgkin 31 kidney 26 lymphoma 28 but 27 , 28 but 28 but 29 low 28 but 31 kidney 32 , 33 stomach 32 , 34 , 34 , 37 colon 34 , 39 and 35 ovarian 36 , 35 ovarian 37 colon 38 , 39 and 39 and 41 cancers 40 lung 41 cancers survival for lung cancer in the uk and ireland was much lower than for other regions for all periods , although results for lung cancer in some regions ( central and eastern europe ) might be affected by overestimation . 0 ###LEFT-WALL### 1 survival 0 ###LEFT-WALL### 10 was 1 survival 2 for 1 survival 10 was 2 for 8 and 3 lung 4 cancer 4 cancer 5 in 4 cancer 8 and 5 in 7 uk 6 the 7 uk 8 and 9 ireland 10 was 12 lower 11 much 12 lower 12 lower 13 than 12 lower 17 for 12 lower 21 although 13 than 14 for 14 for 16 regions 15 other 16 regions 17 for 19 periods 18 all 19 periods 20 , 21 although 21 although 22 results 21 although 37 affected 21 although 40 . 22 results 23 for 22 results 26 in 22 results 35 might 23 for 25 cancer 24 lung 25 cancer 26 in 28 regions 27 some 28 regions 28 regions 31 and 29 ( 31 and 30 central 31 and 31 and 33 europe 31 and 34 ) 32 eastern 33 europe 35 might 36 be 36 be 37 affected 37 affected 38 by 38 by 39 overestimation survival usually decreased with age , although [to] different degrees depending on region [and] cancer type . 0 ###LEFT-WALL### 1 survival 0 ###LEFT-WALL### 16 type 0 ###LEFT-WALL### 17 . 1 survival 3 decreased 2 usually 3 decreased 3 decreased 4 with 3 decreased 7 although 4 with 5 age 6 , 7 although 7 although 10 degrees 9 different 10 degrees 10 degrees 11 depending 10 degrees 16 type 11 depending 12 on 12 on 15 cancer 13 region 15 cancer interpretation : the major advances in cancer management that occurred up to 2007 seem to have resulted in improved survival in europe . 0 ###LEFT-WALL### 1 interpretation 0 ###LEFT-WALL### 2 : 2 : 5 advances 2 : 14 seem 2 : 23 . 3 the 5 advances 4 major 5 advances 5 advances 6 in 5 advances 14 seem 6 in 8 management 7 cancer 8 management 8 management 9 that 8 management 10 occurred 9 that 10 occurred 10 occurred 11 up 10 occurred 12 to 12 to 13 2007 14 seem 15 to 14 seem 17 resulted 15 to 16 have 16 have 17 resulted 17 resulted 18 in 17 resulted 21 in 18 in 20 survival 19 improved 20 survival 21 in 22 europe likely explanations of differences in survival between countries include : differences in stage [at] diagnosis and accessibility to good care , different diagnostic intensity and screening approaches , and differences in cancer biology . 0 ###LEFT-WALL### 1 likely 0 ###LEFT-WALL### 10 : 0 ###LEFT-WALL### 34 . 1 likely 2 explanations 1 likely 9 include 1 likely 10 : 2 explanations 3 of 2 explanations 9 include 3 of 4 differences 4 differences 5 in 4 differences 7 between 5 in 6 survival 7 between 8 countries 10 : 11 differences 10 : 12 in 10 : 18 to 10 : 31 in 12 in 16 and 13 stage 15 diagnosis 15 diagnosis 16 and 16 and 17 accessibility 18 to 29 and 19 good 20 care 20 care 21 , 21 , 24 intensity 21 , 25 and 22 different 24 intensity 23 diagnostic 24 intensity 25 and 27 approaches 25 and 29 and 26 screening 27 approaches 28 , 29 and 29 and 30 differences 31 in 33 biology 32 cancer 33 biology variations in socioeconomic , lifestyle , and general health between populations might also have a role . 0 ###LEFT-WALL### 1 variations 0 ###LEFT-WALL### 14 have 0 ###LEFT-WALL### 17 . 1 variations 2 in 1 variations 12 might 2 in 7 and 3 socioeconomic 4 , 3 socioeconomic 5 lifestyle 5 lifestyle 7 and 6 , 7 and 7 and 9 health 7 and 10 between 8 general 9 health 10 between 11 populations 12 might 14 have 13 also 14 have 14 have 16 role 15 a 16 role further studies are needed to fully interpret these findings and how to remedy disparities . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 4 needed 0 ###LEFT-WALL### 15 . 1 further 2 studies 2 studies 3 are 3 are 4 needed 4 needed 5 to 5 to 7 interpret 6 fully 7 interpret 7 interpret 10 and 7 interpret 12 to 8 these 9 findings 9 findings 10 and 10 and 11 how 12 to 13 remedy 13 remedy 14 disparities funding : italian ministry of health , european commission , compagnia di san paolo foundation , cariplo foundation . 0 ###LEFT-WALL### 1 funding 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 16 , 0 ###LEFT-WALL### 19 . 1 funding 2 : 2 : 15 foundation 3 italian 15 foundation 4 ministry 5 of 4 ministry 11 compagnia 5 of 6 health 6 health 9 commission 7 , 9 commission 8 european 9 commission 9 commission 10 , 11 compagnia 15 foundation 12 di 15 foundation 13 san 14 paolo 14 paolo 15 foundation 16 , 18 foundation 17 cariplo 18 foundation although both impaired cardiac function and reduced cerebral blood flow [are] associated with ageing , current knowledge of the influence of cardiac function [on] resting cerebral blood flow ( cbf ) is limited . 0 ###LEFT-WALL### 17 knowledge 0 ###LEFT-WALL### 32 is 0 ###LEFT-WALL### 34 . 1 although 2 both 1 although 6 and 1 although 17 knowledge 2 both 3 impaired 2 both 6 and 3 impaired 4 cardiac 5 function 6 and 6 and 7 reduced 6 and 10 flow 8 cerebral 9 blood 9 blood 10 flow 10 flow 12 associated 12 associated 13 with 12 associated 15 , 12 associated 16 current 13 with 14 ageing 17 knowledge 18 of 17 knowledge 32 is 18 of 20 influence 19 the 20 influence 20 influence 21 of 20 influence 30 cbf 21 of 28 flow 22 cardiac 23 function 23 function 25 resting 25 resting 28 flow 26 cerebral 27 blood 27 blood 28 flow 29 ( 30 cbf 30 cbf 31 ) 32 is 33 limited the aim of this study was to investigate the potential effects of cardiac function [on] cbf . 0 ###LEFT-WALL### 2 aim 0 ###LEFT-WALL### 17 . 1 the 2 aim 2 aim 3 of 2 aim 6 was 3 of 5 study 4 this 5 study 6 was 7 to 6 was 8 investigate 7 to 8 investigate 8 investigate 11 effects 9 the 11 effects 10 potential 11 effects 11 effects 12 of 12 of 16 cbf 13 cardiac 14 function 14 function 16 cbf cbf and cardiac output were measured in 31 healthy subjects 50 - 75 years old using magnetic resonance imaging techniques . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 5 were 0 ###LEFT-WALL### 21 . 1 cbf 2 and 2 and 4 output 2 and 5 were 3 cardiac 4 output 5 were 6 measured 6 measured 7 in 6 measured 16 using 7 in 10 subjects 8 31 10 subjects 9 healthy 10 subjects 10 subjects 15 old 11 50 12 - 12 - 13 75 12 - 14 years 14 years 15 old 16 using 18 resonance 17 magnetic 18 resonance 18 resonance 19 imaging 19 imaging 20 techniques no effects of cardiac output or cardiac index on cbf or structural signs of brain ageing were observed . 0 ###LEFT-WALL### 11 or 0 ###LEFT-WALL### 18 observed 0 ###LEFT-WALL### 19 . 1 no 2 effects 2 effects 3 of 2 effects 11 or 3 of 6 or 4 cardiac 5 output 5 output 6 or 6 or 8 index 6 or 9 on 7 cardiac 8 index 9 on 10 cbf 11 or 13 signs 11 or 14 of 11 or 17 were 12 structural 13 signs 14 of 16 ageing 15 brain 16 ageing 17 were 18 observed however , fractional brain flow defined as the ratio of total brain flow to cardiac output was inversely correlated with cardiac [index] [(] r ( 2 [ )(= 0.22 , p = 0.008 ) and furthermore lower in males than in females ( 8.6 % versus 12.5 % , p = 0.003 ) . 0 ###LEFT-WALL### 5 flow 0 ###LEFT-WALL### 6 defined 0 ###LEFT-WALL### 54 . 1 however 2 , 1 however 5 flow 3 fractional 4 brain 4 brain 5 flow 5 flow 6 defined 6 defined 7 as 6 defined 42 females 6 defined 51 = 7 as 9 ratio 8 the 9 ratio 9 ratio 10 of 10 of 12 brain 11 total 12 brain 12 brain 13 flow 12 brain 20 with 13 flow 14 to 13 flow 17 was 14 to 16 output 15 cardiac 16 output 17 was 19 correlated 18 inversely 19 correlated 19 correlated 20 with 21 cardiac 28 )(= 21 cardiac 32 = 21 cardiac 35 and 24 r 28 )(= 25 ( 28 )(= 26 2 28 )(= 28 )(= 29 0.22 28 )(= 30 , 30 , 32 = 31 p 32 = 32 = 33 0.008 32 = 34 ) 35 and 36 furthermore 35 and 37 lower 35 and 42 females 37 lower 38 in 37 lower 40 than 38 in 39 males 40 than 41 in 42 females 45 % 43 ( 45 % 44 8.6 45 % 45 % 46 versus 45 % 49 , 46 versus 48 % 47 12.5 48 % 50 p 51 = 51 = 52 0.003 51 = 53 ) fractional brain flow was also inversely correlated with cerebral white matter lesion grade , although this effect was not significant when adjusted for age . 0 ###LEFT-WALL### 3 flow 0 ###LEFT-WALL### 7 correlated 1 fractional 2 brain 2 brain 3 flow 3 flow 4 was 4 was 5 also 4 was 7 correlated 6 inversely 7 correlated 7 correlated 8 with 7 correlated 15 although 8 with 13 grade 9 cerebral 10 white 10 white 11 matter 11 matter 13 grade 12 lesion 13 grade 14 , 15 although 15 although 17 effect 15 although 18 was 15 although 25 . 16 this 17 effect 17 effect 18 was 18 was 19 not 18 was 20 significant 20 significant 21 when 20 significant 23 for 21 when 22 adjusted 23 for 24 age frequency analysis of heart rate variability showed a gender [-] related inverse association of increased low - [to] - high - frequency power ratio [with] cbf and fractional brain flow . 0 ###LEFT-WALL### 2 analysis 0 ###LEFT-WALL### 15 increased 0 ###LEFT-WALL### 17 - 1 frequency 2 analysis 2 analysis 3 of 2 analysis 15 increased 3 of 4 heart 4 heart 6 variability 4 heart 14 of 5 rate 6 variability 6 variability 7 showed 7 showed 13 association 8 a 9 gender 8 a 13 association 9 gender 11 related 11 related 13 association 12 inverse 13 association 13 association 14 of 15 increased 16 low 17 - 19 - 17 - 30 flow 17 - 31 . 19 - 27 and 20 high 21 - 20 high 27 and 22 frequency 23 power 23 power 26 cbf 24 ratio 26 cbf 26 cbf 27 and 27 and 29 brain 27 and 30 flow 28 fractional 29 brain the findings do not support a direct effect [of] cardiac function on cbf , but demonstrates gender - related differences in cardiac output distribution . 0 ###LEFT-WALL### 2 findings 0 ###LEFT-WALL### 15 but 0 ###LEFT-WALL### 19 related 1 the 2 findings 2 findings 15 but 3 do 4 not 3 do 5 support 3 do 15 but 5 support 11 function 5 support 12 on 6 a 7 direct 6 a 11 function 7 direct 8 effect 8 effect 11 function 10 cardiac 11 function 12 on 13 cbf 14 , 15 but 15 but 16 demonstrates 16 demonstrates 17 gender 18 - 19 related 19 related 20 differences 19 related 21 in 19 related 25 . 21 in 24 distribution 22 cardiac 23 output 23 output 24 distribution we propose fractional brain flow as a novel index that may be a useful marker of adequate brain perfusion in the context of ageing as well as cardiovascular disease . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 propose 0 ###LEFT-WALL### 30 . 1 we 2 propose 2 propose 5 flow 3 fractional 4 brain 4 brain 5 flow 5 flow 6 as 5 flow 10 that 5 flow 11 may 6 as 9 index 7 a 9 index 8 novel 9 index 10 that 11 may 11 may 12 be 12 be 15 marker 13 a 15 marker 14 useful 15 marker 15 marker 16 of 15 marker 20 in 15 marker 23 of 15 marker 27 as 16 of 19 perfusion 17 adequate 18 brain 18 brain 19 perfusion 20 in 22 context 21 the 22 context 23 of 24 ageing 25 as 26 well 26 well 27 as 27 as 29 disease 28 cardiovascular 29 disease background : adverse loading conditions and cardiac injury lead to remodelling of the heart into different patterns of left [ventricular] ( lv ) geometry . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 25 . 2 : 6 and 2 : 9 lead 3 adverse 4 loading 3 adverse 6 and 4 loading 5 conditions 6 and 8 injury 6 and 9 lead 7 cardiac 8 injury 9 lead 10 to 9 lead 15 into 10 to 11 remodelling 11 remodelling 12 of 12 of 14 heart 13 the 14 heart 15 into 17 patterns 16 different 17 patterns 17 patterns 18 of 18 of 24 geometry 19 left 22 lv 19 left 24 geometry 21 ( 22 lv 22 lv 23 ) geometry can be classified into lv [hypertrophy] ( lvh ) , [concentric] remodelling [(] cr ) or normal geometry ( ng ) . 0 ###LEFT-WALL### 1 geometry 0 ###LEFT-WALL### 3 be 0 ###LEFT-WALL### 23 . 1 geometry 2 can 2 can 3 be 3 be 19 geometry 4 classified 5 into 4 classified 17 or 5 into 6 lv 6 lv 9 lvh 6 lv 13 remodelling 8 ( 9 lvh 9 lvh 10 ) 11 , 13 remodelling 13 remodelling 15 cr 13 remodelling 16 ) 17 or 18 normal 17 or 19 geometry 19 geometry 21 ng 20 ( 21 ng 21 ng 22 ) the prognostic implications of the different geometric patterns have been extensively studied in middle [-] aged subjects , but data are scarcer for elderly populations . 0 ###LEFT-WALL### 3 implications 0 ###LEFT-WALL### 12 studied 0 ###LEFT-WALL### 19 but 0 ###LEFT-WALL### 26 . 1 the 3 implications 2 prognostic 3 implications 3 implications 4 of 3 implications 9 have 4 of 8 patterns 5 the 8 patterns 6 different 8 patterns 7 geometric 8 patterns 9 have 10 been 10 been 11 extensively 10 been 12 studied 12 studied 13 in 13 in 17 subjects 14 middle 16 aged 16 aged 17 subjects 18 , 19 but 19 but 20 data 19 but 21 are 20 data 21 are 21 are 22 scarcer 22 scarcer 23 for 23 for 25 populations 24 elderly 25 populations methods : from a community [-] based random sample of 75 - year [-] old men and women , subjects with normal lvef were selected ( n = 303 ) . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 19 , 0 ###LEFT-WALL### 31 . 1 methods 2 : 2 : 3 from 3 from 9 sample 4 a 9 sample 5 community 7 based 7 based 9 sample 8 random 9 sample 9 sample 10 of 10 of 11 75 11 75 17 and 12 - 17 and 13 year 16 men 15 old 16 men 16 men 17 and 17 and 18 women 17 and 19 , 19 , 20 subjects 19 , 25 selected 20 subjects 21 with 20 subjects 24 were 21 with 23 lvef 22 normal 23 lvef 24 were 25 selected 25 selected 28 = 26 ( 28 = 27 n 28 = 28 = 29 303 28 = 30 ) [all] - cause and cardiovascular mortality was analysed by lv geometry with cox regression [(] unadjusted and adjusted for sex , prevalent hypertension , smoking , diabetes and prevalent ischaemic heart disease ) . 0 ###LEFT-WALL### 2 - 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 34 . 2 - 3 cause 4 and 6 mortality 4 and 7 was 5 cardiovascular 6 mortality 6 mortality 7 was 7 was 17 and 8 analysed 9 by 8 analysed 11 geometry 8 analysed 16 unadjusted 8 analysed 17 and 9 by 10 lv 11 geometry 12 with 11 geometry 16 unadjusted 12 with 14 regression 13 cox 14 regression 17 and 18 adjusted 17 and 19 for 19 for 28 and 20 sex 21 , 21 , 23 hypertension 21 , 24 , 22 prevalent 23 hypertension 24 , 25 smoking 24 , 26 , 26 , 27 diabetes 26 , 28 and 28 and 32 disease 28 and 33 ) 29 prevalent 31 heart 30 ischaemic 31 heart 31 heart 32 disease median follow - up time was 9.9 years . 0 ###LEFT-WALL### 2 follow 0 ###LEFT-WALL### 3 - 1 median 2 follow 3 - 5 time 3 - 6 was 3 - 9 . 4 up 5 time 5 time 6 was 6 was 8 years 7 9.9 8 years results : prevalence of cr and lvh was 19 [%] and 17 % , respectively . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 3 prevalence 2 : 8 was 3 prevalence 4 of 3 prevalence 8 was 4 of 6 and 5 cr 6 and 6 and 7 lvh 8 was 13 % 8 was 15 respectively 9 19 11 and 11 and 12 17 11 and 13 % 14 , 15 respectively 15 respectively 16 . hazard ratios ( hrs ) for cr [were] 0.93 ( 95 % ci 0.54 - 1.58 ) for all - cause [and] 1.13 ( 0.48 - 2.65 ) for cardiovascular mortality . 0 ###LEFT-WALL### 1 hazard 0 ###LEFT-WALL### 20 - 0 ###LEFT-WALL### 32 . 1 hazard 2 ratios 1 hazard 6 for 1 hazard 18 for 2 ratios 4 hrs 3 ( 4 hrs 4 hrs 5 ) 6 for 7 cr 7 cr 9 0.93 7 cr 13 ci 10 ( 13 ci 11 95 13 ci 12 % 13 ci 13 ci 14 0.54 13 ci 16 1.58 13 ci 17 ) 15 - 16 1.58 16 1.58 17 ) 18 for 19 all 20 - 21 cause 21 cause 23 1.13 21 cause 29 for 23 1.13 26 - 24 ( 26 - 25 0.48 26 - 26 - 27 2.65 26 - 28 ) 29 for 31 mortality 30 cardiovascular 31 mortality hrs for lvh were 2.01 ( 1.30 - 3.10 ) for all - cause [and] 3.55 ( 1.89 - 6.67 ) for cardiovascular mortality . 0 ###LEFT-WALL### 1 hrs 0 ###LEFT-WALL### 4 were 0 ###LEFT-WALL### 13 - 1 hrs 2 for 1 hrs 4 were 2 for 3 lvh 4 were 5 2.01 4 were 8 - 4 were 11 for 6 ( 8 - 7 1.30 8 - 8 - 9 3.10 8 - 10 ) 11 for 12 all 13 - 14 cause 13 - 25 . 14 cause 16 3.55 14 cause 22 for 16 3.55 19 - 17 ( 19 - 18 1.89 19 - 19 - 20 6.67 19 - 21 ) 22 for 24 mortality 23 cardiovascular 24 mortality [as] [non] - proportionality was present in the form of an increasing hazard for lvh , [we] partitioned the [follow] [-] up time at the median event time ( approximately 7 years [ )(and performed cox regression [separately] within each time period . 3 - 4 proportionality 4 proportionality 16 , 5 was 6 present 5 was 16 , 6 present 7 in 6 present 14 for 7 in 9 form 8 the 9 form 9 form 10 of 10 of 13 hazard 11 an 13 hazard 12 increasing 13 hazard 14 for 15 lvh 16 , 18 partitioned 16 , 23 time 19 the 23 time 22 up 23 time 23 time 24 at 23 time 34 )(and 24 at 28 time 25 the 28 time 26 median 27 event 27 event 28 time 29 ( 34 )(and 30 approximately 31 7 31 7 32 years 32 years 34 )(and 34 )(and 37 regression 34 )(and 39 within 34 )(and 43 . 35 performed 37 regression 36 cox 37 regression 39 within 42 period 40 each 42 period 41 time 42 period hrs for lvh during the first period were 1.23 ( 0.63 - 2.42 ) for all - cause [and] 1.79 ( 0.69 - 4.65 ) for cardiovascular mortality , while hrs for the second period were 3.06 ( 1.73 - 5.41 ) for all - cause [and] 6.60 ( 2.82 - 15.39 ) for cardiovascular mortality . 0 ###LEFT-WALL### 1 hrs 0 ###LEFT-WALL### 8 were 0 ###LEFT-WALL### 17 - 0 ###LEFT-WALL### 57 . 1 hrs 2 for 1 hrs 8 were 2 for 3 lvh 3 lvh 4 during 4 during 7 period 5 the 7 period 6 first 7 period 8 were 9 1.23 8 were 15 for 9 1.23 12 - 10 ( 12 - 11 0.63 12 - 12 - 13 2.42 12 - 14 ) 15 for 16 all 17 - 18 cause 18 cause 20 1.79 18 cause 23 - 18 cause 26 for 18 cause 30 while 18 cause 46 cause 18 cause 54 for 21 ( 23 - 22 0.69 23 - 23 - 24 4.65 23 - 25 ) 26 for 28 mortality 27 cardiovascular 28 mortality 29 , 30 while 30 while 31 hrs 30 while 36 were 30 while 45 - 31 hrs 32 for 31 hrs 36 were 32 for 35 period 33 the 34 second 33 the 35 period 36 were 37 3.06 36 were 40 - 36 were 43 for 38 ( 40 - 39 1.73 40 - 40 - 41 5.41 40 - 42 ) 43 for 44 all 46 cause 48 6.60 46 cause 51 - 49 ( 51 - 50 2.82 51 - 51 - 52 15.39 51 - 53 ) 54 for 56 mortality 55 cardiovascular 56 mortality conclusion : in this community - based sample of 75 [-] year - old men and women with normal lvef , lvh was associated with an adverse prognosis during long - term [follow] - up , whereas cr was not . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 6 - 1 conclusion 2 : 2 : 3 in 3 in 5 community 4 this 5 community 6 - 8 sample 6 - 13 - 7 based 8 sample 8 sample 9 of 9 of 12 year 10 75 12 year 13 - 16 and 13 - 21 , 14 old 15 men 15 men 16 and 16 and 17 women 16 and 18 with 18 with 20 lvef 19 normal 20 lvef 21 , 22 lvh 21 , 24 associated 22 lvh 23 was 23 was 24 associated 24 associated 25 with 24 associated 29 during 24 associated 34 - 24 associated 35 up 25 with 28 prognosis 26 an 27 adverse 26 an 28 prognosis 27 adverse 28 prognosis 29 during 32 term 30 long 31 - 30 long 32 term 35 up 37 whereas 36 , 37 whereas 37 whereas 38 cr 37 whereas 39 was 37 whereas 41 . 38 cr 39 was 39 was 40 not [none] background : pulmonary abnormalities are often present in patients infected with the human immunodeficiency virus ( hiv ) . 0 ###LEFT-WALL### 2 background 0 ###LEFT-WALL### 3 : 3 : 5 abnormalities 3 : 6 are 3 : 20 . 4 pulmonary 5 abnormalities 5 abnormalities 6 are 6 are 7 often 6 are 8 present 8 present 9 in 8 present 12 with 9 in 10 patients 10 patients 11 infected 12 with 16 virus 13 the 16 virus 14 human 16 virus 15 immunodeficiency 16 virus 16 virus 18 hiv 17 ( 18 hiv 18 hiv 19 ) objectives : the aim of the study was to determine the prevalence and characteristics [of] , and risk factors [for] , pulmonary abnormalities in hiv - positive patients . 0 ###LEFT-WALL### 1 objectives 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 29 . 2 : 4 aim 2 : 8 was 3 the 4 aim 4 aim 5 of 4 aim 8 was 5 of 7 study 6 the 7 study 8 was 9 to 9 to 17 and 10 determine 13 and 10 determine 17 and 11 the 12 prevalence 12 prevalence 13 and 13 and 14 characteristics 16 , 17 and 17 and 18 risk 17 and 28 patients 18 risk 19 factors 19 factors 23 abnormalities 21 , 23 abnormalities 22 pulmonary 23 abnormalities 23 abnormalities 24 in 23 abnormalities 26 - 24 in 25 hiv 27 positive 28 patients methods : a total of 275 hiv - positive patients [ mean ( ± standard deviation ) age 48.5 ± 6.6 years ] were included in the study [,] of whom 95.6 % had been receiving highly active antiretroviral therapy ( haart ) for a mean ( ± standard deviation ) duration of 11.9 ± 5.4 years . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 8 - 0 ###LEFT-WALL### 58 . 1 methods 2 : 2 : 4 total 3 a 4 total 4 total 5 of 5 of 7 hiv 6 275 7 hiv 8 - 10 patients 8 - 25 included 9 positive 10 patients 10 patients 22 years 10 patients 24 were 11 [ 22 years 12 mean 16 deviation 12 mean 18 age 13 ( 16 deviation 14 ± 16 deviation 15 standard 16 deviation 16 deviation 17 ) 18 age 22 years 19 48.5 22 years 20 ± 22 years 21 6.6 22 years 22 years 23 ] 24 were 25 included 25 included 26 in 26 in 28 study 27 the 28 study 28 study 30 of 28 study 36 receiving 30 of 31 whom 31 whom 33 % 31 whom 35 been 32 95.6 33 % 33 % 34 had 34 had 35 been 36 receiving 40 therapy 36 receiving 44 for 37 highly 38 active 38 active 40 therapy 39 antiretroviral 40 therapy 40 therapy 42 haart 41 ( 42 haart 42 haart 43 ) 44 for 52 duration 45 a 46 mean 45 a 52 duration 46 mean 50 deviation 46 mean 51 ) 46 mean 52 duration 47 ( 50 deviation 48 ± 50 deviation 49 standard 50 deviation 50 deviation 51 ) 52 duration 53 of 53 of 57 years 54 11.9 57 years 55 ± 57 years 56 5.4 57 years the median ( interquartile range ) cd4 lymphocyte count was 541 ( 392 - 813 ) cells/μl , and 92 % of the patients had an undetectable viral load . 0 ###LEFT-WALL### 9 count 0 ###LEFT-WALL### 10 was 0 ###LEFT-WALL### 19 and 0 ###LEFT-WALL### 30 . 1 the 9 count 2 median 5 range 2 median 9 count 3 ( 5 range 4 interquartile 5 range 5 range 6 ) 7 cd4 9 count 8 lymphocyte 9 count 9 count 10 was 10 was 17 cells/μl 11 541 17 cells/μl 12 ( 14 - 13 392 14 - 14 - 15 813 14 - 16 ) 14 - 17 cells/μl 18 , 19 and 19 and 21 % 19 and 25 had 20 92 21 % 21 % 22 of 21 % 25 had 22 of 24 patients 23 the 24 patients 25 had 29 load 26 an 27 undetectable 26 an 29 load 27 undetectable 29 load 28 viral 29 load we determined : [(] 1 [ )(spirometry , static lung volumes , lung diffusing capacity , pulmonary gas exchange and exercise tolerance , [and] ( [2] [ )(the amount of emphysema via a computed tomography ( ct ) [scan] . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 determined 0 ###LEFT-WALL### 8 , 1 we 2 determined 2 determined 3 : 3 : 5 1 3 : 7 )(spirometry 5 1 7 )(spirometry 8 , 20 and 9 static 10 lung 10 lung 11 volumes 11 volumes 12 , 12 , 15 capacity 12 , 16 , 13 lung 14 diffusing 14 diffusing 15 capacity 16 , 19 exchange 16 , 20 and 17 pulmonary 18 gas 18 gas 19 exchange 20 and 22 tolerance 20 and 23 , 20 and 29 amount 21 exercise 22 tolerance 25 ( 29 amount 28 )(the 29 amount 29 amount 30 of 29 amount 37 ct 29 amount 40 . 30 of 31 emphysema 31 emphysema 32 via 32 via 35 tomography 33 a 35 tomography 34 computed 35 tomography 36 ( 37 ct 37 ct 38 ) results : chronic [cough] and expectoration ( 47 % ) and breathlessness during exercise ( 33.9 % ) were commonly reported . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 11 and 2 : 21 reported 2 : 22 . 3 chronic 5 and 5 and 6 expectoration 5 and 9 % 5 and 11 and 7 ( 9 % 8 47 9 % 9 % 10 ) 11 and 12 breathlessness 11 and 13 during 11 and 19 were 13 during 14 exercise 14 exercise 17 % 15 ( 17 % 16 33.9 17 % 17 % 18 ) 19 were 21 reported 20 commonly 21 reported airflow limitation ( al ) was present in 17.2 % , low pulmonary diffusing capacity in 52.2 % and emphysema in 10.5 - 37.7 % of patients , depending on the method used for quantification . 0 ###LEFT-WALL### 2 limitation 0 ###LEFT-WALL### 6 was 0 ###LEFT-WALL### 11 , 0 ###LEFT-WALL### 36 . 1 airflow 2 limitation 2 limitation 4 al 2 limitation 6 was 3 ( 4 al 4 al 5 ) 6 was 7 present 7 present 8 in 8 in 10 % 9 17.2 10 % 11 , 12 low 12 low 19 and 12 low 30 on 12 low 34 for 13 pulmonary 15 capacity 14 diffusing 15 capacity 15 capacity 16 in 15 capacity 19 and 16 in 18 % 17 52.2 18 % 19 and 20 emphysema 20 emphysema 21 in 20 emphysema 29 depending 21 in 22 10.5 22 10.5 25 % 23 - 25 % 24 37.7 25 % 25 % 26 of 25 % 28 , 26 of 27 patients 30 on 32 method 31 the 32 method 32 method 33 used 34 for 35 quantification most of these abnormalities had not been diagnosed or treated previously . 0 ###LEFT-WALL### 4 abnormalities 0 ###LEFT-WALL### 9 or 0 ###LEFT-WALL### 12 . 1 most 2 of 1 most 4 abnormalities 2 of 4 abnormalities 3 these 4 abnormalities 4 abnormalities 9 or 5 had 6 not 5 had 7 been 5 had 9 or 7 been 8 diagnosed 9 or 10 treated 9 or 11 previously smoking exposure and previous tuberculosis were the main risk factors for al , whereas smoking exposure and several variables related to hiv infection appeared to contribute to the risk of emphysema and low diffusing capacity . 0 ###LEFT-WALL### 1 smoking 0 ###LEFT-WALL### 6 were 0 ###LEFT-WALL### 13 , 0 ###LEFT-WALL### 32 and 0 ###LEFT-WALL### 36 . 1 smoking 3 and 1 smoking 6 were 2 exposure 3 and 3 and 5 tuberculosis 4 previous 5 tuberculosis 6 were 10 factors 6 were 11 for 7 the 10 factors 8 main 10 factors 9 risk 10 factors 11 for 12 al 13 , 17 and 13 , 24 appeared 14 whereas 15 smoking 14 whereas 17 and 16 exposure 17 and 17 and 19 variables 17 and 20 related 17 and 21 to 17 and 24 appeared 18 several 19 variables 21 to 23 infection 22 hiv 23 infection 24 appeared 25 to 25 to 32 and 26 contribute 27 to 26 contribute 32 and 27 to 29 risk 28 the 29 risk 29 risk 30 of 30 of 31 emphysema 32 and 33 low 33 low 35 capacity 34 diffusing 35 capacity conclusions : despite haart , pulmonary structural and functional abnormalities are frequent in hiv - positive patients . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 18 . 2 : 10 abnormalities 2 : 11 are 2 : 15 - 3 despite 4 haart 3 despite 5 , 3 despite 10 abnormalities 6 pulmonary 10 abnormalities 7 structural 8 and 8 and 9 functional 8 and 10 abnormalities 10 abnormalities 11 are 11 are 12 frequent 12 frequent 13 in 13 in 14 hiv 15 - 17 patients 16 positive 17 patients they are probably attributable to both environmental ( smoking and tuberculosis ) and hiv - related factors . 0 ###LEFT-WALL### 1 they 0 ###LEFT-WALL### 2 are 0 ###LEFT-WALL### 18 . 1 they 2 are 2 are 3 probably 2 are 4 attributable 4 attributable 5 to 5 to 17 factors 6 both 17 factors 7 environmental 13 and 7 environmental 17 factors 8 ( 13 and 9 smoking 10 and 10 and 11 tuberculosis 10 and 12 ) 10 and 13 and 13 and 14 hiv 13 and 15 - 16 related 17 factors most of these abnormalities remain unnoticed and untreated . 0 ###LEFT-WALL### 4 abnormalities 0 ###LEFT-WALL### 5 remain 0 ###LEFT-WALL### 9 . 1 most 2 of 1 most 4 abnormalities 2 of 4 abnormalities 3 these 4 abnormalities 4 abnormalities 5 remain 5 remain 7 and 6 unnoticed 7 and 7 and 8 untreated given the relatively young age of these patients , these results anticipate a significant health problem in the next few years [as] , thanks to the efficacy of haart , patients survive longer and experience the effects of aging . 0 ###LEFT-WALL### 11 results 0 ###LEFT-WALL### 12 anticipate 0 ###LEFT-WALL### 40 . 1 given 5 age 1 given 9 , 1 given 11 results 2 the 5 age 3 relatively 4 young 4 young 5 age 5 age 6 of 6 of 8 patients 7 these 8 patients 10 these 11 results 11 results 12 anticipate 12 anticipate 16 problem 12 anticipate 17 in 13 a 16 problem 14 significant 15 health 15 health 16 problem 17 in 21 years 18 the 19 next 18 the 20 few 20 few 21 years 21 years 31 patients 21 years 34 and 23 , 25 to 24 thanks 25 to 25 to 27 efficacy 25 to 30 , 25 to 31 patients 26 the 27 efficacy 27 efficacy 28 of 28 of 29 haart 31 patients 34 and 32 survive 33 longer 32 survive 34 and 34 and 35 experience 35 experience 37 effects 36 the 37 effects 37 effects 38 of 38 of 39 aging background and purpose : white matter hyperintensities ( wmhs ) and brain atrophy frequently coexist in older people . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 15 coexist 0 ###LEFT-WALL### 19 . 1 background 3 purpose 1 background 12 brain 1 background 15 coexist 2 and 3 purpose 3 purpose 4 : 4 : 11 and 5 white 7 hyperintensities 5 white 11 and 6 matter 7 hyperintensities 7 hyperintensities 9 wmhs 8 ( 9 wmhs 9 wmhs 10 ) 11 and 12 brain 12 brain 13 atrophy 14 frequently 15 coexist 15 coexist 16 in 16 in 18 people 17 older 18 people however , it is unclear whether the association between these two brain lesions is dependent on the aging process , a vascular mechanism or genetic susceptibility . 0 ###LEFT-WALL### 3 it 0 ###LEFT-WALL### 4 is 0 ###LEFT-WALL### 20 , 0 ###LEFT-WALL### 27 . 1 however 2 , 1 however 3 it 3 it 4 is 4 is 5 unclear 5 unclear 6 whether 6 whether 8 association 6 whether 14 is 7 the 8 association 8 association 9 between 8 association 14 is 9 between 13 lesions 10 these 11 two 11 two 13 lesions 12 brain 13 lesions 14 is 15 dependent 15 dependent 16 on 16 on 19 process 17 the 19 process 18 aging 19 process 20 , 24 or 21 a 23 mechanism 22 vascular 23 mechanism 23 mechanism 24 or 24 or 26 susceptibility 25 genetic 26 susceptibility it was therefore investigated whether the association between load [of] wmhs and brain atrophy measures is related to age , vascular risk factors ( vrfs [ )(or the apoe - ε4 allele . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 31 ε4 0 ###LEFT-WALL### 33 . 1 it 2 was 2 was 3 therefore 3 therefore 23 factors 4 investigated 5 whether 4 investigated 20 , 4 investigated 23 factors 5 whether 7 association 5 whether 17 related 6 the 7 association 7 association 8 between 7 association 16 is 8 between 12 and 9 load 11 wmhs 11 wmhs 12 and 12 and 15 measures 13 brain 15 measures 14 atrophy 15 measures 16 is 17 related 17 related 18 to 18 to 19 age 21 vascular 23 factors 22 risk 23 factors 23 factors 27 )(or 23 factors 31 ε4 24 ( 27 )(or 25 vrfs 27 )(or 27 )(or 29 apoe 27 )(or 30 - 28 the 29 apoe 31 ε4 32 allele methods : this population - based study included 492 participants ( age ≥60 years , 59.6 % women ) free of dementia and stroke . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 5 - 0 ###LEFT-WALL### 25 . 1 methods 2 : 2 : 4 population 3 this 4 population 5 - 23 and 6 based 7 study 6 based 23 and 7 study 8 included 7 study 10 participants 7 study 20 free 7 study 21 of 9 492 10 participants 10 participants 14 years 10 participants 20 free 11 ( 14 years 12 age 14 years 13 ≥60 14 years 14 years 18 women 14 years 19 ) 15 , 18 women 16 59.6 18 women 17 % 18 women 18 women 19 ) 21 of 22 dementia 23 and 24 stroke data on demographics , vrfs and apoe [genotypes] were collected through interviews , clinical examination and laboratory tests . 0 ###LEFT-WALL### 6 and 0 ###LEFT-WALL### 9 were 0 ###LEFT-WALL### 19 . 1 data 2 on 1 data 4 , 2 on 3 demographics 4 , 5 vrfs 4 , 6 and 6 and 7 apoe 6 and 9 were 9 were 10 collected 10 collected 11 through 11 through 16 and 12 interviews 13 , 13 , 15 examination 13 , 16 and 14 clinical 15 examination 16 and 18 tests 17 laboratory 18 tests wmhs on magnetic resonance images were assessed using manual visual rating and automatic volumetric segmentation . 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 16 . 1 wmhs 2 on 1 wmhs 7 assessed 1 wmhs 12 and 2 on 4 resonance 3 magnetic 4 resonance 4 resonance 5 images 4 resonance 6 were 5 images 6 were 7 assessed 8 using 8 using 11 rating 9 manual 11 rating 10 visual 11 rating 12 and 15 segmentation 13 automatic 15 segmentation 14 volumetric 15 segmentation hippocampal and [ventricular] volumes were manually delineated , whereas total gray matter ( gm ) volume was measured by automatic segmentation . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 7 delineated 0 ###LEFT-WALL### 8 , 0 ###LEFT-WALL### 22 . 1 hippocampal 2 and 2 and 4 volumes 2 and 5 were 5 were 7 delineated 6 manually 7 delineated 8 , 16 volume 8 , 17 was 9 whereas 12 matter 9 whereas 16 volume 10 total 11 gray 11 gray 12 matter 12 matter 14 gm 13 ( 14 gm 14 gm 15 ) 16 volume 17 was 17 was 18 measured 18 measured 19 by 19 by 21 segmentation 20 automatic 21 segmentation data were analyzed with multivariate linear regression models . 0 ###LEFT-WALL### 1 data 0 ###LEFT-WALL### 3 analyzed 0 ###LEFT-WALL### 9 . 1 data 2 were 2 were 3 analyzed 3 analyzed 4 with 4 with 8 models 5 multivariate 8 models 6 linear 7 regression 7 regression 8 models results : more global wmhs , assessed using either a visual rating scale or a volumetric approach , were significantly associated with lower gm volume and higher [ventricular] volume ; the associations remained significant after adjusting for age , vrfs and the apoe - ε4 allele . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 45 ε4 0 ###LEFT-WALL### 47 . 2 : 5 wmhs 2 : 21 associated 2 : 30 ; 3 more 5 wmhs 4 global 5 wmhs 5 wmhs 7 assessed 5 wmhs 19 were 6 , 7 assessed 7 assessed 8 using 7 assessed 18 , 8 using 14 or 9 either 14 or 10 a 13 scale 11 visual 13 scale 12 rating 13 scale 13 scale 14 or 14 or 17 approach 14 or 18 , 15 a 17 approach 16 volumetric 17 approach 19 were 20 significantly 19 were 21 associated 21 associated 22 with 22 with 24 gm 22 with 26 and 23 lower 24 gm 25 volume 26 and 26 and 29 volume 26 and 30 ; 27 higher 29 volume 30 ; 32 associations 30 ; 33 remained 31 the 32 associations 32 associations 33 remained 33 remained 34 significant 34 significant 35 after 35 after 36 adjusting 36 adjusting 37 for 37 for 41 and 38 age 39 , 39 , 40 vrfs 39 , 41 and 41 and 43 apoe 41 and 44 - 41 and 45 ε4 42 the 43 apoe 45 ε4 46 allele in contrast , the association between global wmhs and hippocampal volume was no longer significant after adjusting for age , whereas adjustment for vrfs and apoe - ε4 had no influential effect . 0 ###LEFT-WALL### 5 association 0 ###LEFT-WALL### 20 , 0 ###LEFT-WALL### 33 . 1 in 2 contrast 1 in 3 , 1 in 5 association 4 the 5 association 5 association 6 between 5 association 12 was 6 between 9 and 7 global 8 wmhs 8 wmhs 9 and 9 and 11 volume 10 hippocampal 11 volume 12 was 14 longer 12 was 15 significant 13 no 14 longer 15 significant 16 after 16 after 17 adjusting 17 adjusting 18 for 18 for 19 age 20 , 28 ε4 20 , 29 had 21 whereas 22 adjustment 21 whereas 27 - 21 whereas 28 ε4 22 adjustment 23 for 23 for 25 and 24 vrfs 25 and 25 and 26 apoe 25 and 27 - 28 ε4 29 had 29 had 32 effect 30 no 32 effect 31 influential 32 effect conclusion : the association of global wmhs with lower gm volume and higher [ventricular] volume is independent of age , vrfs and apoe - ε4 allele , suggesting that the process of cerebral microvascular disease and neurodegeneration [are] associated independently of the normal aging process , vascular mechanisms or genetic susceptibility . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 12 and 1 conclusion 2 : 2 : 4 association 3 the 4 association 4 association 5 of 5 of 7 wmhs 6 global 7 wmhs 7 wmhs 8 with 8 with 11 volume 9 lower 11 volume 10 gm 11 volume 12 and 15 volume 13 higher 15 volume 15 volume 16 is 16 is 22 and 17 independent 18 of 17 independent 20 , 18 of 19 age 20 , 21 vrfs 20 , 22 and 22 and 23 apoe 22 and 27 , 22 and 28 suggesting 23 apoe 26 allele 24 - 26 allele 25 ε4 26 allele 26 allele 27 , 27 , 28 suggesting 28 suggesting 36 and 29 that 36 and 30 the 31 process 31 process 32 of 31 process 36 and 32 of 35 disease 33 cerebral 35 disease 34 microvascular 35 disease 36 and 37 neurodegeneration 36 and 39 associated 39 associated 40 independently 40 independently 41 of 41 of 45 process 42 the 45 process 43 normal 45 process 44 aging 45 process 45 process 49 or 46 , 49 or 47 vascular 48 mechanisms 48 mechanisms 49 or 49 or 51 susceptibility 49 or 52 . 50 genetic 51 susceptibility this descriptive study examined the relationship between volunteer activities , depressive symptoms , and feelings of usefulness among older adults using path analysis . 0 ###LEFT-WALL### 3 study 0 ###LEFT-WALL### 4 examined 0 ###LEFT-WALL### 24 . 1 this 2 descriptive 2 descriptive 3 study 3 study 4 examined 4 examined 6 relationship 4 examined 7 between 4 examined 18 among 5 the 6 relationship 7 between 14 and 8 volunteer 9 activities 9 activities 10 , 10 , 12 symptoms 10 , 14 and 11 depressive 12 symptoms 13 , 14 and 14 and 15 feelings 14 and 16 of 16 of 17 usefulness 18 among 20 adults 19 older 20 adults 20 adults 21 using 21 using 23 analysis 22 path 23 analysis survey data was collected via interview [from] residents of a continuing care retirement community . 0 ###LEFT-WALL### 2 data 0 ###LEFT-WALL### 3 was 0 ###LEFT-WALL### 15 . 1 survey 2 data 2 data 3 was 3 was 4 collected 4 collected 5 via 5 via 8 residents 6 interview 8 residents 8 residents 9 of 9 of 14 community 10 a 14 community 11 continuing 12 care 12 care 14 community 13 retirement 14 community neither feelings of usefulness nor volunteering were directly associated with depressive symptoms . 0 ###LEFT-WALL### 5 nor 0 ###LEFT-WALL### 9 associated 0 ###LEFT-WALL### 13 . 1 neither 5 nor 2 feelings 3 of 2 feelings 5 nor 3 of 4 usefulness 5 nor 6 volunteering 5 nor 7 were 7 were 9 associated 8 directly 9 associated 9 associated 10 with 10 with 12 symptoms 11 depressive 12 symptoms volunteering was directly associated with feelings of usefulness and indirectly associated with depressive symptoms through total physical activity . 0 ###LEFT-WALL### 1 volunteering 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 19 . 1 volunteering 9 and 2 was 4 associated 2 was 9 and 3 directly 4 associated 4 associated 5 with 5 with 6 feelings 6 feelings 7 of 7 of 8 usefulness 9 and 11 associated 9 and 12 with 9 and 15 through 10 indirectly 11 associated 12 with 14 symptoms 13 depressive 14 symptoms 15 through 18 activity 16 total 18 activity 17 physical 18 activity age , fear of falling , pain , physical activity , and physical resilience explained 31 % of the variance in depressive symptoms . 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 15 explained 0 ###LEFT-WALL### 24 . 1 age 3 fear 1 age 12 and 2 , 3 fear 3 fear 4 of 3 fear 7 pain 3 fear 11 , 4 of 5 falling 6 , 7 pain 7 pain 10 activity 7 pain 11 , 8 , 10 activity 9 physical 10 activity 10 activity 11 , 11 , 12 and 12 and 14 resilience 12 and 15 explained 13 physical 14 resilience 15 explained 17 % 15 explained 21 in 16 31 17 % 17 % 18 of 18 of 20 variance 19 the 20 variance 21 in 23 symptoms 22 depressive 23 symptoms engaging in volunteer work may be beneficial for increasing feelings of usefulness and indirectly improving depressive symptoms among older adults . 0 ###LEFT-WALL### 1 engaging 0 ###LEFT-WALL### 6 be 0 ###LEFT-WALL### 21 . 1 engaging 2 in 1 engaging 5 may 2 in 4 work 3 volunteer 4 work 5 may 6 be 6 be 7 beneficial 7 beneficial 8 for 8 for 9 increasing 9 increasing 13 and 9 increasing 18 among 10 feelings 11 of 10 feelings 13 and 11 of 12 usefulness 13 and 17 symptoms 14 indirectly 15 improving 15 improving 16 depressive 16 depressive 17 symptoms 18 among 20 adults 19 older 20 adults the social environment impacts the ability of older adults to interact successfully with their community and age - in - place . 0 ###LEFT-WALL### 3 environment 0 ###LEFT-WALL### 4 impacts 0 ###LEFT-WALL### 20 - 0 ###LEFT-WALL### 22 . 1 the 3 environment 2 social 3 environment 3 environment 4 impacts 4 impacts 6 ability 5 the 6 ability 6 ability 7 of 6 ability 10 to 6 ability 11 interact 7 of 9 adults 8 older 9 adults 10 to 11 interact 11 interact 12 successfully 11 interact 13 with 13 with 16 and 13 with 19 in 14 their 15 community 15 community 16 and 16 and 17 age 18 - 19 in 20 - 21 place focus groups were conducted at 3 retirement communities . 0 ###LEFT-WALL### 2 groups 0 ###LEFT-WALL### 4 conducted 0 ###LEFT-WALL### 9 . 1 focus 2 groups 2 groups 3 were 3 were 4 conducted 4 conducted 5 at 5 at 8 communities 6 3 8 communities 7 retirement 8 communities analysis found common categories across focus groups that explain the phenomenon of lgbt senior housing . 0 ###LEFT-WALL### 1 analysis 0 ###LEFT-WALL### 2 found 0 ###LEFT-WALL### 16 . 1 analysis 2 found 2 found 4 categories 2 found 15 housing 3 common 4 categories 4 categories 5 across 4 categories 8 that 4 categories 9 explain 5 across 7 groups 6 focus 7 groups 8 that 9 explain 9 explain 11 phenomenon 10 the 11 phenomenon 11 phenomenon 12 of 12 of 13 lgbt 14 senior 15 housing acceptance is paramount for lgbt seniors and social networks expanded , contrary to socioemotional selectivity theory . 0 ###LEFT-WALL### 1 acceptance 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 17 . 1 acceptance 2 is 2 is 9 networks 3 paramount 4 for 3 paramount 7 and 4 for 6 seniors 5 lgbt 6 seniors 7 and 8 social 7 and 9 networks 9 networks 10 expanded 10 expanded 11 , 10 expanded 12 contrary 12 contrary 13 to 13 to 16 theory 14 socioemotional 15 selectivity 15 selectivity 16 theory providers are encouraged to develop safe spaces for lgbt seniors . 0 ###LEFT-WALL### 1 providers 0 ###LEFT-WALL### 3 encouraged 0 ###LEFT-WALL### 11 . 1 providers 2 are 2 are 3 encouraged 3 encouraged 4 to 3 encouraged 5 develop 4 to 5 develop 5 develop 7 spaces 6 safe 7 spaces 7 spaces 8 for 8 for 10 seniors 9 lgbt 10 seniors objective : injections of human placental extract , which is known to play a role in skin regulation , have long been used for the treatment of skin wrinkles [and] [non] - healing wounds . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 8 , 0 ###LEFT-WALL### 23 used 1 objective 2 : 2 : 3 injections 3 injections 4 of 4 of 7 extract 5 human 7 extract 6 placental 7 extract 8 , 9 which 8 , 11 known 8 , 19 , 9 which 10 is 10 is 11 known 11 known 12 to 11 known 13 play 12 to 13 play 13 play 15 role 13 play 16 in 14 a 15 role 16 in 18 regulation 17 skin 18 regulation 19 , 20 have 20 have 22 been 21 long 22 been 22 been 23 used 23 used 24 for 23 used 33 healing 24 for 26 treatment 25 the 26 treatment 26 treatment 27 of 27 of 29 wrinkles 28 skin 29 wrinkles 32 - 33 healing 33 healing 34 wounds 33 healing 35 . porcine placental extract ( ppe ) , an oral supplement , was recently developed for this purpose . 0 ###LEFT-WALL### 3 extract 0 ###LEFT-WALL### 14 developed 0 ###LEFT-WALL### 18 . 1 porcine 3 extract 2 placental 3 extract 3 extract 5 ppe 3 extract 10 supplement 3 extract 12 was 4 ( 5 ppe 5 ppe 6 ) 7 , 10 supplement 8 an 9 oral 8 an 10 supplement 9 oral 10 supplement 10 supplement 11 , 12 was 14 developed 13 recently 14 developed 14 developed 15 for 15 for 17 purpose 16 this 17 purpose the aim of this study was to assess whether ppe has a positive effect on the improvement of fine wrinkles below the eye in climacteric women . 0 ###LEFT-WALL### 2 aim 0 ###LEFT-WALL### 27 . 1 the 2 aim 2 aim 3 of 2 aim 6 was 3 of 5 study 4 this 5 study 6 was 7 to 6 was 8 assess 7 to 8 assess 8 assess 9 whether 8 assess 24 in 9 whether 10 ppe 9 whether 11 has 10 ppe 11 has 11 has 14 effect 11 has 15 on 11 has 21 below 12 a 13 positive 12 a 14 effect 13 positive 14 effect 15 on 17 improvement 16 the 17 improvement 17 improvement 18 of 18 of 20 wrinkles 19 fine 20 wrinkles 21 below 23 eye 22 the 23 eye 24 in 26 women 25 climacteric 26 women methods : we first [non] - invasively measured wrinkle widths with a skin analyzer in a cross - section [of] 185 healthy adult japanese women . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 4 first 2 : 19 section 2 : 26 . 3 we 4 first 4 first 10 widths 4 first 19 section 6 - 10 widths 7 invasively 8 measured 8 measured 10 widths 9 wrinkle 10 widths 10 widths 11 with 10 widths 14 analyzer 10 widths 18 - 11 with 13 skin 12 a 13 skin 14 analyzer 15 in 15 in 17 cross 16 a 17 cross 19 section 25 women 21 185 25 women 22 healthy 23 adult 23 adult 24 japanese 24 japanese 25 women next , 44 climacteric women with mild or few climacteric symptoms were enrolled into an open - label , randomized , controlled study of the effect of ppe on wrinkle widths . 0 ###LEFT-WALL### 5 women 0 ###LEFT-WALL### 21 , 0 ###LEFT-WALL### 32 . 1 next 2 , 1 next 5 women 3 44 5 women 4 climacteric 5 women 5 women 6 with 5 women 21 , 6 with 8 or 7 mild 8 or 8 or 11 symptoms 9 few 11 symptoms 10 climacteric 11 symptoms 12 were 13 enrolled 12 were 21 , 13 enrolled 14 into 13 enrolled 19 , 13 enrolled 20 randomized 14 into 18 label 15 an 16 open 15 an 18 label 16 open 17 - 16 open 18 label 21 , 22 controlled 21 , 29 on 22 controlled 23 study 23 study 24 of 24 of 26 effect 25 the 26 effect 26 effect 27 of 27 of 28 ppe 29 on 31 widths 30 wrinkle 31 widths a retrospective comparison of wrinkle widths in 123 climacteric women with climacteric symptoms [with] or without ppe treatment was also performed . 0 ###LEFT-WALL### 3 comparison 0 ###LEFT-WALL### 21 performed 0 ###LEFT-WALL### 22 . 1 a 2 retrospective 1 a 3 comparison 2 retrospective 3 comparison 3 comparison 4 of 3 comparison 19 was 4 of 6 widths 5 wrinkle 6 widths 6 widths 7 in 7 in 10 women 8 123 10 women 9 climacteric 10 women 10 women 15 or 11 with 13 symptoms 11 with 15 or 12 climacteric 13 symptoms 15 or 16 without 16 without 18 treatment 17 ppe 18 treatment 19 was 21 performed 20 also 21 performed results : wrinkle widths below the eye in women ≥ 30 years of age were significantly higher than in women 20 - 29 years of age . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 27 . 1 results 2 : 2 : 3 wrinkle 3 wrinkle 4 widths 3 wrinkle 5 below 3 wrinkle 8 in 5 below 7 eye 6 the 7 eye 8 in 24 years 9 women 10 ≥ 10 ≥ 22 - 11 30 12 years 11 30 22 - 12 years 13 of 12 years 15 were 13 of 14 age 15 were 17 higher 16 significantly 17 higher 17 higher 18 than 17 higher 19 in 19 in 20 women 20 women 21 20 22 - 23 29 23 29 24 years 24 years 25 of 25 of 26 age treatment with three capsules of ppe per day was significantly ( p < 0.05 ) effective in reducing wrinkle widths at 24 weeks compared with control subjects . 0 ###LEFT-WALL### 1 treatment 0 ###LEFT-WALL### 28 . 1 treatment 2 with 1 treatment 5 of 1 treatment 9 was 2 with 4 capsules 3 three 4 capsules 5 of 6 ppe 6 ppe 7 per 7 per 8 day 9 was 10 significantly 9 was 13 < 9 was 16 effective 11 ( 13 < 12 p 13 < 13 < 14 0.05 13 < 15 ) 16 effective 17 in 17 in 18 reducing 18 reducing 20 widths 19 wrinkle 20 widths 20 widths 21 at 20 widths 24 compared 21 at 23 weeks 22 24 23 weeks 24 compared 25 with 25 with 27 subjects 26 control 27 subjects retrospective analysis showed that subjects treated with three ( p < 0.05 ) and six ( p < 0.01 ) capsules of ppe per day observed a significant reduction in wrinkle widths compared with untreated subjects . 0 ###LEFT-WALL### 2 analysis 0 ###LEFT-WALL### 3 showed 0 ###LEFT-WALL### 37 . 1 retrospective 2 analysis 2 analysis 3 showed 3 showed 4 that 3 showed 5 subjects 3 showed 14 and 3 showed 34 with 5 subjects 6 treated 5 subjects 11 < 6 treated 7 with 7 with 8 three 9 ( 11 < 10 p 11 < 11 < 12 0.05 11 < 13 ) 14 and 15 six 14 and 21 capsules 15 six 18 < 16 ( 18 < 17 p 18 < 18 < 19 0.01 18 < 20 ) 21 capsules 22 of 22 of 23 ppe 23 ppe 24 per 23 ppe 26 observed 23 ppe 29 reduction 23 ppe 33 compared 24 per 25 day 27 a 28 significant 27 a 29 reduction 28 significant 29 reduction 29 reduction 30 in 29 reduction 33 compared 30 in 32 widths 31 wrinkle 32 widths 34 with 36 subjects 35 untreated 36 subjects conclusion : oral ppe treatment is a possible option for improving the appearance of fine wrinkles below the eye in climacteric women . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 23 . 2 : 5 treatment 2 : 6 is 3 oral 4 ppe 4 ppe 5 treatment 5 treatment 6 is 6 is 9 option 7 a 8 possible 7 a 9 option 8 possible 9 option 9 option 10 for 9 option 14 of 10 for 11 improving 11 improving 13 appearance 12 the 13 appearance 14 of 16 wrinkles 15 fine 16 wrinkles 16 wrinkles 17 below 17 below 19 eye 18 the 19 eye 19 eye 20 in 20 in 22 women 21 climacteric 22 women judaism has a positive attitude to sexual relations within a marriage , and views such sexual relations as important [not] only [for] [procreation] but also as part of the framework of marriage . 0 ###LEFT-WALL### 1 judaism 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 33 . 1 judaism 13 and 2 has 5 attitude 2 has 6 to 2 has 9 within 2 has 13 and 3 a 4 positive 3 a 5 attitude 4 positive 5 attitude 6 to 8 relations 7 sexual 8 relations 9 within 11 marriage 10 a 11 marriage 12 , 13 and 13 and 14 views 13 and 17 relations 15 such 17 relations 16 sexual 17 relations 17 relations 19 important 18 as 19 important 19 important 21 only 19 important 24 but 19 important 26 as 24 but 25 also 26 as 27 part 26 as 31 of 27 part 28 of 28 of 30 framework 29 the 30 framework 31 of 32 marriage this is true for any age group , and sexuality is seen as an essential element of marriage for couples of advanced age . 0 ###LEFT-WALL### 1 this 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 24 . 1 this 2 is 2 is 3 true 3 true 4 for 4 for 7 group 5 any 7 group 6 age 7 group 8 , 9 and 9 and 10 sexuality 9 and 12 seen 10 sexuality 11 is 11 is 12 seen 12 seen 13 as 13 as 16 element 14 an 15 essential 14 an 16 element 15 essential 16 element 16 element 17 of 17 of 18 marriage 18 marriage 19 for 19 for 20 couples 20 couples 21 of 21 of 23 age 22 advanced 23 age in this article , the authors present the views of jewish law and thought regarding sexuality among older couples . 0 ###LEFT-WALL### 6 authors 0 ###LEFT-WALL### 7 present 0 ###LEFT-WALL### 20 . 1 in 3 article 1 in 4 , 1 in 6 authors 2 this 3 article 5 the 6 authors 6 authors 7 present 7 present 9 views 8 the 9 views 9 views 10 of 9 views 15 regarding 10 of 13 and 11 jewish 12 law 12 law 13 and 13 and 14 thought 15 regarding 16 sexuality 16 sexuality 17 among 17 among 19 couples 18 older 19 couples the authors illustrate this using 3 case studies of couples who sought guidance in the area of sexuality . 0 ###LEFT-WALL### 2 authors 0 ###LEFT-WALL### 3 illustrate 0 ###LEFT-WALL### 19 . 1 the 2 authors 2 authors 3 illustrate 3 illustrate 4 this 3 illustrate 5 using 5 using 8 studies 5 using 14 in 6 3 8 studies 7 case 8 studies 8 studies 9 of 9 of 10 couples 10 couples 11 who 10 couples 12 sought 11 who 12 sought 12 sought 13 guidance 14 in 16 area 15 the 16 area 16 area 17 of 17 of 18 sexuality in addition , this area of counseling benefits greatly from an ongoing relationship and dialogue between expert rabbis in the field and therapists treating older orthodox jewish patients for sexual dysfunction . 0 ###LEFT-WALL### 5 area 0 ###LEFT-WALL### 8 benefits 0 ###LEFT-WALL### 32 . 1 in 2 addition 1 in 3 , 1 in 5 area 4 this 5 area 5 area 6 of 5 area 8 benefits 6 of 7 counseling 8 benefits 9 greatly 8 benefits 10 from 8 benefits 28 patients 8 benefits 29 for 10 from 14 and 11 an 13 relationship 12 ongoing 13 relationship 13 relationship 14 and 14 and 15 dialogue 15 dialogue 16 between 15 dialogue 24 treating 16 between 18 rabbis 17 expert 18 rabbis 18 rabbis 19 in 19 in 22 and 20 the 21 field 21 field 22 and 22 and 23 therapists 24 treating 26 orthodox 25 older 26 orthodox 27 jewish 28 patients 29 for 31 dysfunction 30 sexual 31 dysfunction the triad relationship [of] couple , therapist , and rabbi enhances the ability to treat and assist such couples to seek treatment and overcome their difficulties . 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 27 . 1 the 5 couple 2 triad 5 couple 3 relationship 5 couple 5 couple 6 , 6 , 7 therapist 6 , 9 and 8 , 9 and 9 and 10 rabbi 9 and 23 and 11 enhances 13 ability 11 enhances 23 and 12 the 13 ability 13 ability 14 to 13 ability 16 and 14 to 16 and 15 treat 16 and 16 and 17 assist 17 assist 19 couples 17 assist 20 to 18 such 19 couples 20 to 21 seek 21 seek 22 treatment 23 and 24 overcome 23 and 26 difficulties 25 their 26 difficulties strong evidence suggests that systemic inflammation and central adiposity [contribute] to [and] perpetuate metabolic syndrome . 0 ###LEFT-WALL### 2 evidence 0 ###LEFT-WALL### 3 suggests 0 ###LEFT-WALL### 16 . 1 strong 2 evidence 2 evidence 3 suggests 3 suggests 15 syndrome 4 that 15 syndrome 5 systemic 6 inflammation 6 inflammation 7 and 7 and 9 adiposity 7 and 11 to 7 and 13 perpetuate 7 and 15 syndrome 8 central 9 adiposity 11 to 13 perpetuate 14 metabolic 15 syndrome all of these alterations predispose individuals to type 2 diabetes mellitus ( t2dm ) , cardiovascular disease , as well as alzheimer 's disease ( ad ) , all characterized by chronic inflammatory status . 0 ###LEFT-WALL### 1 all 0 ###LEFT-WALL### 28 , 0 ###LEFT-WALL### 35 . 1 all 2 of 1 all 28 , 2 of 4 alterations 3 these 4 alterations 5 predispose 6 individuals 5 predispose 21 as 5 predispose 28 , 6 individuals 7 to 6 individuals 17 disease 7 to 11 mellitus 8 type 10 diabetes 9 2 10 diabetes 10 diabetes 11 mellitus 11 mellitus 13 t2dm 12 ( 13 t2dm 13 t2dm 14 ) 15 , 17 disease 16 cardiovascular 17 disease 17 disease 18 , 18 , 21 as 19 as 20 well 20 well 21 as 21 as 24 disease 21 as 27 ) 22 alzheimer 23 's 23 's 24 disease 24 disease 26 ad 25 ( 26 ad 26 ad 27 ) 28 , 30 characterized 28 , 31 by 29 all 30 characterized 31 by 34 status 32 chronic 34 status 33 inflammatory 34 status on the other hand , extensive abnormalities in insulin and insulin - like growth factor i ( igf - i ) and igf [-] ii signaling mechanisms in brains with ad have been demonstrated , suggesting that ad could be a third form of diabetes . 0 ###LEFT-WALL### 36 suggesting 0 ###LEFT-WALL### 40 be 0 ###LEFT-WALL### 46 . 1 on 4 hand 1 on 36 suggesting 2 the 3 other 3 other 4 hand 4 hand 7 abnormalities 5 , 7 abnormalities 6 extensive 7 abnormalities 7 abnormalities 8 in 7 abnormalities 35 , 8 in 22 and 9 insulin 10 and 10 and 11 insulin 10 and 12 - 10 and 13 like 10 and 19 - 10 and 22 and 13 like 15 factor 14 growth 15 factor 15 factor 16 i 17 ( 19 - 18 igf 19 - 19 - 20 i 19 - 21 ) 22 and 23 igf 22 and 26 signaling 22 and 27 mechanisms 22 and 33 been 22 and 34 demonstrated 23 igf 25 ii 27 mechanisms 28 in 27 mechanisms 32 have 28 in 29 brains 29 brains 30 with 30 with 31 ad 32 have 33 been 36 suggesting 37 that 36 suggesting 40 be 37 that 38 ad 37 that 39 could 38 ad 39 could 40 be 43 form 41 a 43 form 42 third 43 form 43 form 44 of 44 of 45 diabetes the src homology domain - containing inositol 5 - phosphatase 2 ( ship2 ) has an important role in the insulin pathway because its [over] [-] expression causes impairment of insulin/igf - 1 signaling . 0 ###LEFT-WALL### 4 domain 0 ###LEFT-WALL### 15 has 0 ###LEFT-WALL### 32 - 0 ###LEFT-WALL### 35 . 1 the 4 domain 2 src 3 homology 3 homology 4 domain 4 domain 6 containing 4 domain 15 has 5 - 6 containing 6 containing 7 inositol 6 containing 14 ) 7 inositol 8 5 7 inositol 10 phosphatase 9 - 10 phosphatase 10 phosphatase 11 2 10 phosphatase 13 ship2 10 phosphatase 14 ) 12 ( 13 ship2 13 ship2 14 ) 15 has 18 role 15 has 19 in 15 has 23 because 16 an 17 important 16 an 18 role 17 important 18 role 19 in 22 pathway 20 the 22 pathway 21 insulin 22 pathway 23 because 27 expression 23 because 28 causes 24 its 27 expression 27 expression 28 causes 28 causes 29 impairment 29 impairment 30 of 30 of 31 insulin/igf 32 - 33 1 33 1 34 signaling because some single [-] nucleotide polymorphisms ( snp ) [of] the gene encoding ship2 were significantly associated in t2dm patients with metabolic syndrome and some related conditions , we decided to conduct a case - control study on this gene , analyzing ad and t2dm subjects as cases and young , old , and centenarians as controls . 1 because 2 some 1 because 3 single 1 because 12 gene 2 some 3 single 3 single 6 polymorphisms 5 nucleotide 6 polymorphisms 7 ( 8 snp 8 snp 9 ) 8 snp 12 gene 11 the 12 gene 12 gene 13 encoding 12 gene 15 were 13 encoding 14 ship2 15 were 16 significantly 15 were 17 associated 17 associated 18 in 18 in 24 and 19 t2dm 20 patients 20 patients 21 with 20 patients 24 and 21 with 23 syndrome 22 metabolic 23 syndrome 24 and 25 some 24 and 26 related 24 and 27 conditions 24 and 36 control 27 conditions 36 control 28 , 30 decided 29 we 30 decided 30 decided 31 to 30 decided 35 - 30 decided 36 control 31 to 32 conduct 32 conduct 34 case 33 a 34 case 36 control 37 study 36 control 42 analyzing 37 study 38 on 38 on 40 gene 39 this 40 gene 41 , 42 analyzing 42 analyzing 49 and 43 ad 44 and 44 and 46 subjects 44 and 47 as 44 and 49 and 45 t2dm 46 subjects 47 as 48 cases 49 and 50 young 49 and 54 and 51 , 54 and 52 old 54 and 53 , 54 and 54 and 55 centenarians 54 and 56 as 54 and 58 . 56 as 57 controls our results suggest a putative correlation between [the] the rs144989913 snp and aging , both successful and unsuccessful , rather than age - related diseases . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 suggest 0 ###LEFT-WALL### 14 , 0 ###LEFT-WALL### 26 . 1 our 2 results 2 results 3 suggest 3 suggest 6 correlation 4 a 5 putative 4 a 6 correlation 5 putative 6 correlation 6 correlation 7 between 7 between 12 and 9 the 10 rs144989913 10 rs144989913 11 snp 11 snp 12 and 12 and 13 aging 12 and 14 , 14 , 25 diseases 15 both 25 diseases 16 successful 17 and 17 and 18 unsuccessful 17 and 25 diseases 18 unsuccessful 21 than 19 , 21 than 20 rather 21 than 21 than 22 age 21 than 23 - 24 related 25 diseases because this snp is an insertion/deletion of 28 bp , it might cause an alteration in ship2 expression . 0 ###LEFT-WALL### 11 it 0 ###LEFT-WALL### 13 cause 0 ###LEFT-WALL### 19 . 1 because 3 snp 1 because 4 is 1 because 10 , 1 because 11 it 2 this 3 snp 3 snp 4 is 4 is 6 insertion/deletion 5 an 6 insertion/deletion 6 insertion/deletion 7 of 7 of 9 bp 8 28 9 bp 11 it 12 might 12 might 13 cause 13 cause 15 alteration 13 cause 16 in 14 an 15 alteration 16 in 18 expression 17 ship2 18 expression it is [noteworthy] that ship2 has been demonstrated to be a potent negative regulator of insulin signaling and insulin sensitivity . 0 ###LEFT-WALL### 10 be 0 ###LEFT-WALL### 21 . 1 it 2 is 2 is 4 that 4 that 5 ship2 4 that 8 demonstrated 5 ship2 6 has 6 has 7 been 7 been 8 demonstrated 8 demonstrated 9 to 9 to 10 be 10 be 14 regulator 11 a 12 potent 11 a 14 regulator 12 potent 14 regulator 13 negative 14 regulator 14 regulator 15 of 15 of 18 and 16 insulin 17 signaling 16 insulin 18 and 18 and 20 sensitivity 19 insulin 20 sensitivity many studies demonstrated the association of the insulin/igf1 pathway with aging and longevity , so it is tempting to speculate that the [found] association with ship2 and aging might depend on its effect on the insulin/igf - 1 pathway . 0 ###LEFT-WALL### 1 many 0 ###LEFT-WALL### 15 so 0 ###LEFT-WALL### 17 is 0 ###LEFT-WALL### 40 . 2 studies 3 demonstrated 3 demonstrated 5 association 3 demonstrated 15 so 4 the 5 association 5 association 6 of 6 of 12 and 7 the 9 pathway 8 insulin/igf1 9 pathway 9 pathway 10 with 9 pathway 12 and 10 with 11 aging 12 and 13 longevity 14 , 15 so 15 so 16 it 16 it 17 is 17 is 18 tempting 18 tempting 19 to 18 tempting 39 pathway 19 to 20 speculate 20 speculate 21 that 21 that 24 association 21 that 30 depend 22 the 24 association 24 association 25 with 24 association 29 might 25 with 27 and 26 ship2 27 and 27 and 28 aging 29 might 30 depend 30 depend 31 on 30 depend 34 on 31 on 33 effect 32 its 33 effect 34 on 36 insulin/igf 35 the 36 insulin/igf 37 - 38 1 38 1 39 pathway remembering complex events requires binding features within unified objects ( conjunctions ) and holding associations between objects ( relations ) . 0 ###LEFT-WALL### 1 remembering 0 ###LEFT-WALL### 4 requires 0 ###LEFT-WALL### 21 . 1 remembering 3 events 1 remembering 4 requires 2 complex 3 events 4 requires 13 and 4 requires 16 between 5 binding 6 features 6 features 7 within 6 features 13 and 7 within 9 objects 8 unified 9 objects 9 objects 11 conjunctions 10 ( 11 conjunctions 11 conjunctions 12 ) 13 and 15 associations 14 holding 15 associations 16 between 17 objects 17 objects 19 relations 18 ( 19 relations 19 relations 20 ) recent studies suggest that the two functions dissociate [in] long - term memory ( ltm ) . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 3 suggest 0 ###LEFT-WALL### 17 . 1 recent 2 studies 2 studies 3 suggest 3 suggest 4 that 4 that 7 functions 4 that 8 dissociate 5 the 6 two 6 two 7 functions 7 functions 8 dissociate 8 dissociate 13 memory 10 long 11 - 10 long 12 term 12 term 13 memory 13 memory 15 ltm 14 ( 15 ltm 15 ltm 16 ) less is known about their functional organization in short - term memory ( stm ) . 0 ###LEFT-WALL### 1 less 0 ###LEFT-WALL### 3 known 0 ###LEFT-WALL### 16 . 1 less 2 is 2 is 3 known 3 known 4 about 3 known 8 in 4 about 7 organization 5 their 7 organization 6 functional 7 organization 8 in 12 memory 9 short 10 - 9 short 11 term 11 term 12 memory 12 memory 14 stm 13 ( 14 stm 14 stm 15 ) the present study investigated this issue in patient ae affected by a stroke which caused damage to brain regions known to be relevant for relational functions both in ltm and in stm ( i.e [.] , the hippocampus ) . 0 ###LEFT-WALL### 3 study 0 ###LEFT-WALL### 26 functions 1 the 3 study 2 present 3 study 3 study 4 investigated 4 investigated 6 issue 5 this 6 issue 6 issue 7 in 6 issue 17 to 6 issue 20 known 7 in 9 ae 8 patient 9 ae 9 ae 10 affected 9 ae 11 by 9 ae 14 which 9 ae 15 caused 11 by 13 stroke 12 a 13 stroke 14 which 15 caused 15 caused 16 damage 17 to 19 regions 18 brain 19 regions 20 known 21 to 20 known 24 for 21 to 22 be 22 be 23 relevant 24 for 25 relational 25 relational 26 functions 26 functions 27 both 27 both 30 and 28 in 29 ltm 28 in 30 and 30 and 31 in 31 in 32 stm 32 stm 34 i.e 33 ( 34 i.e 34 i.e 38 hippocampus 34 i.e 40 . 36 , 38 hippocampus 37 the 38 hippocampus 38 hippocampus 39 ) the assessment involved a battery of standard neuropsychological tasks and stm binding tasks . 0 ###LEFT-WALL### 2 assessment 0 ###LEFT-WALL### 3 involved 0 ###LEFT-WALL### 14 . 1 the 2 assessment 2 assessment 3 involved 3 involved 5 battery 4 a 5 battery 5 battery 6 of 5 battery 12 binding 6 of 10 and 7 standard 9 tasks 8 neuropsychological 9 tasks 9 tasks 10 and 10 and 11 stm 12 binding 13 tasks one stm binding task ( experiment 1 ) presented common objects and common colors forming either pairs ( relations ) or integrated objects ( conjunctions ) . 0 ###LEFT-WALL### 4 task 0 ###LEFT-WALL### 21 or 0 ###LEFT-WALL### 27 . 1 one 4 task 2 stm 3 binding 3 binding 4 task 4 task 6 experiment 4 task 21 or 5 ( 6 experiment 6 experiment 7 1 6 experiment 8 ) 9 presented 12 and 9 presented 21 or 10 common 11 objects 11 objects 12 and 12 and 14 colors 12 and 15 forming 12 and 17 pairs 12 and 19 relations 13 common 14 colors 15 forming 17 pairs 16 either 17 pairs 18 ( 19 relations 19 relations 20 ) 21 or 22 integrated 22 integrated 23 objects 23 objects 25 conjunctions 24 ( 25 conjunctions 25 conjunctions 26 ) free recall of relations or conjunctions was assessed . 0 ###LEFT-WALL### 2 recall 0 ###LEFT-WALL### 8 assessed 0 ###LEFT-WALL### 9 . 1 free 2 recall 2 recall 3 of 2 recall 7 was 3 of 5 or 4 relations 5 or 5 or 6 conjunctions 7 was 8 assessed [a] second stm binding task used random polygons and [non] [-] primary colors instead ( experiment 2 ) . 0 ###LEFT-WALL### 2 second 0 ###LEFT-WALL### 19 . 2 second 3 stm 3 stm 4 binding 3 stm 16 experiment 4 binding 9 and 4 binding 14 instead 5 task 6 used 6 used 8 polygons 7 random 8 polygons 8 polygons 9 and 9 and 13 colors 12 primary 13 colors 15 ( 16 experiment 16 experiment 17 2 16 experiment 18 ) memory was assessed by selecting the features that made up the relations or the conjunctions from a set of single polygons and a set of single colors . 0 ###LEFT-WALL### 1 memory 0 ###LEFT-WALL### 3 assessed 0 ###LEFT-WALL### 28 . 1 memory 2 was 2 was 3 assessed 3 assessed 4 by 4 by 5 selecting 5 selecting 7 features 6 the 7 features 7 features 8 that 7 features 9 made 8 that 9 made 9 made 10 up 9 made 13 or 9 made 16 from 11 the 12 relations 12 relations 13 or 13 or 15 conjunctions 14 the 15 conjunctions 16 from 18 set 17 a 18 set 18 set 19 of 19 of 22 and 20 single 21 polygons 21 polygons 22 and 22 and 24 set 22 and 25 of 23 a 24 set 25 of 27 colors 26 single 27 colors the neuropsychological assessment revealed impaired delayed memory in ae . 0 ###LEFT-WALL### 3 assessment 0 ###LEFT-WALL### 6 delayed 0 ###LEFT-WALL### 10 . 1 the 3 assessment 2 neuropsychological 3 assessment 3 assessment 4 revealed 3 assessment 5 impaired 3 assessment 6 delayed 6 delayed 7 memory 6 delayed 8 in 8 in 9 ae ae 's pronounced relational stm binding deficits contrasted with his completely preserved conjunctive binding functions in both experiments 1 and 2 . 0 ###LEFT-WALL### 5 stm 0 ###LEFT-WALL### 15 functions 0 ###LEFT-WALL### 22 . 1 ae 2 's 2 's 5 stm 3 pronounced 5 stm 4 relational 5 stm 5 stm 6 binding 5 stm 9 with 5 stm 15 functions 6 binding 7 deficits 7 deficits 8 contrasted 9 with 13 conjunctive 10 his 13 conjunctive 11 completely 12 preserved 12 preserved 13 conjunctive 13 conjunctive 14 binding 15 functions 16 in 16 in 18 experiments 17 both 18 experiments 18 experiments 20 and 19 1 20 and 20 and 21 2 only 2.35 [%] and 1.14 % of the population were expected to have a discrepancy more extreme than that presented by ae in experiments 1 and 2 , respectively . 0 ###LEFT-WALL### 6 % 0 ###LEFT-WALL### 11 expected 1 only 2 2.35 2 2.35 4 and 4 and 5 1.14 4 and 6 % 6 % 7 of 6 % 10 were 7 of 9 population 8 the 9 population 10 were 11 expected 11 expected 12 to 11 expected 13 have 12 to 13 have 13 have 15 discrepancy 14 a 15 discrepancy 15 discrepancy 17 extreme 15 discrepancy 20 presented 16 more 17 extreme 17 extreme 18 than 18 than 19 that 20 presented 21 by 20 presented 23 in 20 presented 29 respectively 21 by 22 ae 23 in 24 experiments 24 experiments 26 and 25 1 26 and 26 and 27 2 28 , 29 respectively 29 respectively 30 . processing relations and conjunctions of very elementary nonspatial features in stm led to dissociating performances in ae . 0 ###LEFT-WALL### 1 processing 0 ###LEFT-WALL### 12 led 0 ###LEFT-WALL### 18 . 1 processing 3 and 1 processing 10 in 1 processing 12 led 2 relations 3 and 3 and 4 conjunctions 3 and 5 of 5 of 9 features 6 very 7 elementary 7 elementary 9 features 8 nonspatial 9 features 10 in 11 stm 12 led 13 to 12 led 16 in 13 to 14 dissociating 14 dissociating 15 performances 16 in 17 ae these findings may inform current theories of memory [decline] such as those linked to cognitive aging . 0 ###LEFT-WALL### 2 findings 0 ###LEFT-WALL### 4 inform 0 ###LEFT-WALL### 17 . 1 these 2 findings 2 findings 3 may 3 may 4 inform 4 inform 6 theories 5 current 6 theories 6 theories 7 of 7 of 8 memory 8 memory 11 as 10 such 11 as 11 as 12 those 12 those 13 linked 13 linked 14 to 14 to 16 aging 15 cognitive 16 aging this study aims to provide empirical evidence regarding whether attitudes , beliefs , and intentions of elder - service providers can be positively affected as a result of attending cultural competency training on the unique challenges of sexual and gender minorities . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 aims 0 ###LEFT-WALL### 42 . 1 this 2 study 2 study 3 aims 3 aims 4 to 4 to 5 provide 5 provide 7 evidence 5 provide 33 on 6 empirical 7 evidence 7 evidence 8 regarding 8 regarding 9 whether 8 regarding 25 as 8 regarding 32 training 9 whether 14 and 9 whether 22 be 10 attitudes 11 , 11 , 12 beliefs 11 , 14 and 13 , 14 and 14 and 15 intentions 14 and 16 of 14 and 21 can 16 of 20 providers 17 elder 18 - 17 elder 19 service 19 service 20 providers 21 can 22 be 22 be 23 positively 22 be 24 affected 25 as 27 result 26 a 27 result 27 result 28 of 28 of 29 attending 29 attending 31 competency 30 cultural 31 competency 33 on 36 challenges 34 the 36 challenges 35 unique 36 challenges 36 challenges 37 of 37 of 41 minorities 38 sexual 39 and 39 and 40 gender 39 and 41 minorities stigmatization throughout the lifespan may have a causal influence on barriers to care , social isolation , and concomitant health disparities . 0 ###LEFT-WALL### 4 lifespan 0 ###LEFT-WALL### 6 have 0 ###LEFT-WALL### 22 . 1 stigmatization 4 lifespan 2 throughout 4 lifespan 3 the 4 lifespan 4 lifespan 5 may 5 may 6 have 6 have 9 influence 6 have 10 on 6 have 12 to 7 a 8 causal 7 a 9 influence 8 causal 9 influence 10 on 11 barriers 12 to 18 and 13 care 14 , 14 , 16 isolation 14 , 18 and 15 social 16 isolation 17 , 18 and 18 and 21 disparities 19 concomitant 20 health 20 health 21 disparities data were collected for this study at 4 massachusetts training events to pilot a cultural competency workshop [on] lesbian , gay , bisexual , and transgender ( lgbt ) aging for mainstream elder service providers . 0 ###LEFT-WALL### 1 data 0 ###LEFT-WALL### 2 were 0 ###LEFT-WALL### 36 . 1 data 2 were 2 were 3 collected 3 collected 4 for 3 collected 7 at 3 collected 12 to 3 collected 13 pilot 4 for 6 study 5 this 6 study 7 at 11 events 8 4 11 events 9 massachusetts 10 training 10 training 11 events 12 to 13 pilot 13 pilot 30 aging 13 pilot 31 for 14 a 19 lesbian 15 cultural 16 competency 16 competency 19 lesbian 17 workshop 19 lesbian 19 lesbian 20 , 20 , 21 gay 20 , 22 , 22 , 23 bisexual 22 , 25 and 24 , 25 and 25 and 26 transgender 25 and 28 lgbt 25 and 30 aging 27 ( 28 lgbt 28 lgbt 29 ) 31 for 35 providers 32 mainstream 34 service 33 elder 34 service 34 service 35 providers this [quasi] - experimental study included the analysis of pre - and posttest surveys completed by the service - provider attendees ( n = 76 ) . 0 ###LEFT-WALL### 1 this 0 ###LEFT-WALL### 3 - 3 - 5 study 3 - 6 included 3 - 27 . 4 experimental 5 study 5 study 6 included 6 included 12 and 6 included 16 by 7 the 8 analysis 8 analysis 9 of 8 analysis 12 and 9 of 10 pre 11 - 12 and 12 and 14 surveys 12 and 15 completed 13 posttest 14 surveys 16 by 18 service 17 the 18 service 18 service 21 attendees 19 - 21 attendees 20 provider 21 attendees 21 attendees 24 = 21 attendees 26 ) 22 ( 24 = 23 n 24 = 24 = 25 76 the analytic strategy included descriptive statistics , paired [t] tests , chi - square analyses , and repeated measures analyses of variance . 0 ###LEFT-WALL### 3 strategy 0 ###LEFT-WALL### 19 measures 0 ###LEFT-WALL### 23 . 1 the 3 strategy 2 analytic 3 strategy 3 strategy 17 and 3 strategy 19 measures 4 included 6 statistics 4 included 17 and 5 descriptive 6 statistics 6 statistics 10 tests 7 , 10 tests 8 paired 10 tests 10 tests 12 chi 10 tests 15 analyses 10 tests 16 , 11 , 12 chi 12 chi 13 - 13 - 15 analyses 14 square 15 analyses 15 analyses 16 , 17 and 18 repeated 19 measures 20 analyses 20 analyses 21 of 21 of 22 variance findings revealed statistically significant improvement in numerous aspects of providers ' knowledge , attitudes , and behavioral intentions subsequent to the training sessions . 0 ###LEFT-WALL### 1 findings 0 ###LEFT-WALL### 2 revealed 0 ###LEFT-WALL### 13 , 0 ###LEFT-WALL### 24 . 1 findings 2 revealed 2 revealed 5 improvement 3 statistically 4 significant 4 significant 5 improvement 5 improvement 6 in 6 in 8 aspects 7 numerous 8 aspects 8 aspects 9 of 9 of 12 knowledge 10 providers 11 ' 11 ' 12 knowledge 13 , 16 and 14 attitudes 16 and 15 , 16 and 16 and 18 intentions 16 and 19 subsequent 17 behavioral 18 intentions 19 subsequent 20 to 20 to 23 sessions 21 the 23 sessions 22 training 23 sessions these included ( p = [.] 000 ) awareness of lgbt resources , policy disparities , spousal benefits for same - sex couples , and the intention to challenge homophobic remarks . 0 ###LEFT-WALL### 1 these 0 ###LEFT-WALL### 2 included 0 ###LEFT-WALL### 13 , 0 ###LEFT-WALL### 32 . 1 these 2 included 2 included 5 = 2 included 9 awareness 3 ( 5 = 4 p 5 = 5 = 7 000 5 = 8 ) 9 awareness 10 of 10 of 12 resources 11 lgbt 12 resources 13 , 15 disparities 13 , 22 sex 14 policy 15 disparities 15 disparities 18 benefits 15 disparities 22 sex 16 , 18 benefits 17 spousal 18 benefits 18 benefits 19 for 18 benefits 21 - 19 for 20 same 22 sex 25 and 22 sex 28 to 23 couples 25 and 24 , 25 and 25 and 27 intention 26 the 27 intention 28 to 29 challenge 29 challenge 31 remarks 30 homophobic 31 remarks this study concludes that mainstream elder - service provider training on lgbt aging issues results in positive change . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 concludes 0 ###LEFT-WALL### 19 . 1 this 2 study 2 study 3 concludes 3 concludes 4 that 4 that 10 training 4 that 14 issues 5 mainstream 10 training 6 elder 7 - 6 elder 8 service 8 service 10 training 9 provider 10 training 10 training 11 on 10 training 13 aging 10 training 14 issues 11 on 12 lgbt 14 issues 15 results 15 results 16 in 16 in 18 change 17 positive 18 change recommendations include long - term [follow] up [of] participants , the inception [of] agency - level surveys to appraise institutional culture change , and increased curriculum on transgender older adults . 0 ###LEFT-WALL### 1 recommendations 0 ###LEFT-WALL### 2 include 0 ###LEFT-WALL### 31 . 1 recommendations 2 include 2 include 17 surveys 2 include 18 to 2 include 27 on 3 long 9 participants 3 long 16 level 4 - 9 participants 5 term 9 participants 7 up 9 participants 9 participants 14 agency 9 participants 15 - 10 , 14 agency 11 the 14 agency 12 inception 14 agency 14 agency 15 - 16 level 17 surveys 18 to 19 appraise 19 appraise 24 and 20 institutional 21 culture 21 culture 22 change 22 change 24 and 23 , 24 and 24 and 26 curriculum 25 increased 26 curriculum 27 on 30 adults 28 transgender 30 adults 29 older 30 adults this study examines the association of sexual identity and gender among older clients with hiv at an aids service organization using the andersen model . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 examines 0 ###LEFT-WALL### 25 . 1 this 2 study 2 study 3 examines 3 examines 5 association 4 the 5 association 5 association 6 of 6 of 9 and 7 sexual 8 identity 8 identity 9 and 9 and 10 gender 9 and 11 among 11 among 13 clients 12 older 13 clients 13 clients 14 with 13 clients 16 at 14 with 15 hiv 16 at 20 organization 17 an 20 organization 18 aids 19 service 19 service 20 organization 20 organization 21 using 21 using 24 model 22 the 24 model 23 andersen 24 model data confirm those aging with hiv exhibit high rates of age - associated illnesses 10 to 20 years before expected . 0 ###LEFT-WALL### 1 data 0 ###LEFT-WALL### 2 confirm 0 ###LEFT-WALL### 12 - 0 ###LEFT-WALL### 21 . 1 data 2 confirm 2 confirm 3 those 2 confirm 7 exhibit 3 those 4 aging 3 those 7 exhibit 4 aging 5 with 5 with 6 hiv 7 exhibit 9 rates 8 high 9 rates 9 rates 10 of 10 of 11 age 12 - 14 illnesses 13 associated 14 illnesses 14 illnesses 19 before 14 illnesses 20 expected 15 10 16 to 16 to 17 20 16 to 18 years 18 years 19 before they have fragile social networks that cannot supply the informal supports needed . 0 ###LEFT-WALL### 1 they 0 ###LEFT-WALL### 2 have 0 ###LEFT-WALL### 13 . 1 they 2 have 2 have 5 networks 3 fragile 5 networks 4 social 5 networks 5 networks 6 that 5 networks 7 cannot 6 that 7 cannot 7 cannot 8 supply 8 supply 11 supports 9 the 11 supports 10 informal 11 supports 11 supports 12 needed this aging population will need to increasingly access community [-] based services . 0 ###LEFT-WALL### 3 population 0 ###LEFT-WALL### 5 need 0 ###LEFT-WALL### 13 . 1 this 2 aging 2 aging 3 population 3 population 4 will 4 will 5 need 5 need 6 to 5 need 8 access 6 to 8 access 7 increasingly 8 access 8 access 12 services 9 community 11 based 11 based 12 services sexual identity and gender were weak covariates of service utilization . 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 5 were 0 ###LEFT-WALL### 11 . 1 sexual 2 identity 2 identity 3 and 3 and 4 gender 3 and 5 were 5 were 7 covariates 6 weak 7 covariates 7 covariates 8 of 8 of 10 utilization 9 service 10 utilization although heterosexual men used more services , utilization was largely predicted by service needs and the use of case management . 0 ###LEFT-WALL### 8 utilization 0 ###LEFT-WALL### 11 predicted 0 ###LEFT-WALL### 21 . 1 although 3 men 1 although 4 used 1 although 7 , 1 although 8 utilization 2 heterosexual 3 men 3 men 4 used 4 used 6 services 5 more 6 services 8 utilization 9 was 9 was 11 predicted 10 largely 11 predicted 11 predicted 12 by 12 by 15 and 13 service 14 needs 14 needs 15 and 15 and 17 use 15 and 18 of 16 the 17 use 18 of 20 management 19 case 20 management implications for service delivery and policy are discussed . 0 ###LEFT-WALL### 1 implications 0 ###LEFT-WALL### 8 discussed 0 ###LEFT-WALL### 9 . 1 implications 2 for 1 implications 7 are 2 for 5 and 3 service 4 delivery 4 delivery 5 and 5 and 6 policy 7 are 8 discussed african americans elders , like their [non] [-] african american counterparts , are not a homogeneous group ; however an early characteristic placed on all african americans is in their shared history in the united states . 0 ###LEFT-WALL### 3 elders 0 ###LEFT-WALL### 13 are 0 ###LEFT-WALL### 18 ; 0 ###LEFT-WALL### 37 . 1 african 2 americans 2 americans 3 elders 3 elders 5 like 3 elders 13 are 4 , 5 like 5 like 11 counterparts 5 like 12 , 6 their 11 counterparts 9 african 11 counterparts 10 american 11 counterparts 13 are 14 not 13 are 17 group 15 a 16 homogeneous 15 a 17 group 16 homogeneous 17 group 18 ; 22 characteristic 18 ; 28 is 19 however 22 characteristic 20 an 21 early 20 an 22 characteristic 21 early 22 characteristic 22 characteristic 23 placed 22 characteristic 28 is 23 placed 24 on 24 on 27 americans 25 all 27 americans 26 african 27 americans 28 is 29 in 28 is 33 in 29 in 32 history 30 their 32 history 31 shared 32 history 33 in 36 states 34 the 36 states 35 united 36 states as members of multiple minority groups , older lesbian , gay , bisexual , and transgender ( lgbt ) people of african descent have survived racism , heterosexism , homophobia , and now ageism . 0 ###LEFT-WALL### 20 people 0 ###LEFT-WALL### 25 survived 0 ###LEFT-WALL### 35 . 1 as 2 members 1 as 19 ) 1 as 20 people 2 members 3 of 2 members 18 lgbt 3 of 15 and 4 multiple 5 minority 5 minority 6 groups 6 groups 7 , 7 , 9 lesbian 7 , 10 , 8 older 9 lesbian 10 , 11 gay 10 , 12 , 12 , 13 bisexual 12 , 15 and 14 , 15 and 15 and 16 transgender 17 ( 18 lgbt 18 lgbt 19 ) 20 people 21 of 20 people 24 have 21 of 23 descent 22 african 23 descent 24 have 25 survived 25 survived 32 and 26 racism 27 , 27 , 30 homophobia 27 , 32 and 28 heterosexism 29 , 28 heterosexism 30 homophobia 31 , 32 and 32 and 33 now 32 and 34 ageism this article describes a qualitative study grounded in black feminist and minority stress theories that explored the issues of perceived social discrimination and alienation of 15 older african american lesbians and gay males whose [lived] experiences were captured using in - depth , face - to [-] face interviews . 0 ###LEFT-WALL### 2 article 0 ###LEFT-WALL### 3 describes 1 this 2 article 2 article 3 describes 3 describes 6 study 4 a 6 study 5 qualitative 6 study 6 study 7 grounded 6 study 11 and 6 study 13 stress 7 grounded 8 in 8 in 9 black 10 feminist 11 and 11 and 12 minority 11 and 13 stress 13 stress 14 theories 14 theories 15 that 14 theories 16 explored 14 theories 19 of 14 theories 25 of 15 that 16 explored 16 explored 18 issues 17 the 18 issues 19 of 23 and 20 perceived 21 social 21 social 22 discrimination 22 discrimination 23 and 23 and 24 alienation 25 of 31 and 26 15 30 lesbians 27 older 29 american 28 african 29 american 29 american 30 lesbians 30 lesbians 31 and 31 and 32 gay 31 and 33 males 31 and 40 in 31 and 42 depth 33 males 34 whose 33 males 38 captured 34 whose 36 experiences 36 experiences 37 were 38 captured 39 using 38 captured 40 in 41 - 42 depth 42 depth 44 face 42 depth 46 to 42 depth 50 . 43 , 44 face 44 face 45 - 45 - 46 to 46 to 49 interviews 46 to 50 . 48 face 49 interviews several themes were identified in the study , including [(] a [ )(sense of alienation in the african american community [,] [(] [b] [ )(deliberate concealment of sexual identity and orientation [,] [(] [c] ) aversion to lgbt labels , [(] [d] [ )(perceived discrimination and alienation from organized religion [,] [(] [e] [ )(feelings of grief and loss related to aging , ( [f] [ )(isolation , and [(] [g] [ )(fear of financial and physical dependence . 0 ###LEFT-WALL### 2 themes 0 ###LEFT-WALL### 4 identified 1 several 2 themes 2 themes 3 were 3 were 4 identified 4 identified 5 in 4 identified 9 including 5 in 7 study 6 the 7 study 8 , 9 including 9 including 13 )(sense 11 a 13 )(sense 13 )(sense 14 of 13 )(sense 16 in 14 of 15 alienation 16 in 26 concealment 17 the 19 american 18 african 19 american 19 american 26 concealment 20 community 25 )(deliberate 25 )(deliberate 26 concealment 26 concealment 27 of 27 of 36 aversion 28 sexual 29 identity 29 identity 30 and 30 and 31 orientation 30 and 35 ) 30 and 36 aversion 36 aversion 37 to 37 to 46 and 38 lgbt 39 labels 39 labels 40 , 40 , 45 discrimination 40 , 46 and 44 )(perceived 45 discrimination 46 and 55 )(feelings 46 and 56 of 47 alienation 48 from 48 from 55 )(feelings 49 organized 50 religion 50 religion 55 )(feelings 56 of 58 and 57 grief 58 and 58 and 60 related 58 and 63 , 58 and 69 and 59 loss 60 related 60 related 61 to 61 to 62 aging 64 ( 69 and 67 )(isolation 69 and 68 , 69 and 69 and 73 )(fear 69 and 74 of 69 and 79 . 74 of 76 and 75 financial 76 and 76 and 78 dependence 77 physical 78 dependence the implication of the findings suggests that the ethos and needs of older african american lesbian women and gay men need to be addressed to eliminate potential barriers to successful aging for this cohort . 0 ###LEFT-WALL### 2 implication 0 ###LEFT-WALL### 6 suggests 0 ###LEFT-WALL### 35 . 1 the 2 implication 2 implication 3 of 2 implication 6 suggests 3 of 5 findings 4 the 5 findings 6 suggests 7 that 7 that 10 and 7 that 21 need 8 the 9 ethos 9 ethos 10 and 10 and 11 needs 10 and 12 of 12 of 18 and 13 older 17 women 14 african 16 lesbian 15 american 16 lesbian 16 lesbian 17 women 17 women 18 and 18 and 20 men 19 gay 20 men 21 need 22 to 21 need 32 for 22 to 23 be 23 be 24 addressed 24 addressed 25 to 24 addressed 29 to 25 to 26 eliminate 26 eliminate 28 barriers 27 potential 28 barriers 29 to 31 aging 30 successful 31 aging 32 for 34 cohort 33 this 34 cohort lesbian , gay , bisexual , and transgender ( lgbt ) persons in the county of riverside , ca and in the palm springs/coachella valley area , in particular , responded to a questionnaire addressing concerns about identity disclosure and comfort accessing social services . 0 ###LEFT-WALL### 1 lesbian 0 ###LEFT-WALL### 2 , 0 ###LEFT-WALL### 45 . 2 , 19 ca 2 , 20 and 3 gay 12 persons 3 gay 19 ca 4 , 12 persons 5 bisexual 7 and 6 , 7 and 7 and 8 transgender 7 and 10 lgbt 7 and 12 persons 9 ( 10 lgbt 10 lgbt 11 ) 12 persons 13 in 12 persons 16 of 12 persons 18 , 13 in 15 county 14 the 15 county 16 of 17 riverside 20 and 26 area 20 and 31 responded 21 in 25 valley 21 in 26 area 22 the 25 valley 23 palm 24 springs/coachella 24 springs/coachella 25 valley 26 area 29 particular 26 area 31 responded 27 , 29 particular 28 in 29 particular 29 particular 30 , 31 responded 32 to 32 to 40 and 33 a 34 questionnaire 34 questionnaire 35 addressing 34 questionnaire 40 and 35 addressing 36 concerns 36 concerns 37 about 37 about 39 disclosure 38 identity 39 disclosure 40 and 41 comfort 40 and 42 accessing 42 accessing 44 services 43 social 44 services distributed at a pride festival , [as] well as through religious , social , and service agencies , the final sample for analysis of 502 comprised 401 [(] 80 % [ )(gay men and 101 [(] 20 % [ )(lesbians in 4 groups [:] [<] 50 years of age ( 18 % [ )(, [50] to 59 [(] [26] % [ )(, 60 to 69 ( 36 % ) , [and] over 70 ( 20 % ) . 0 ###LEFT-WALL### 6 , 1 distributed 2 at 1 distributed 5 festival 1 distributed 6 , 2 at 4 pride 3 a 4 pride 6 , 8 well 8 well 15 and 9 as 10 through 10 through 13 social 11 religious 12 , 11 religious 13 social 13 social 15 and 14 , 15 and 15 and 17 agencies 15 and 18 , 15 and 20 final 15 and 21 sample 15 and 24 of 16 service 17 agencies 19 the 20 final 20 final 21 sample 21 sample 22 for 22 for 23 analysis 24 of 34 and 25 502 26 comprised 26 comprised 32 )(gay 27 401 32 )(gay 29 80 30 % 30 % 32 )(gay 32 )(gay 33 men 33 men 34 and 34 and 40 )(lesbians 35 101 40 )(lesbians 37 20 38 % 38 % 40 )(lesbians 40 )(lesbians 41 in 41 in 47 years 42 4 47 years 43 groups 47 years 46 50 47 years 47 years 48 of 47 years 56 to 48 of 49 age 49 age 52 % 50 ( 52 % 51 18 52 % 52 % 54 )(, 56 to 60 % 57 59 60 % 60 % 64 to 60 % 72 over 62 )(, 64 to 63 60 64 to 64 to 65 69 64 to 68 % 64 to 70 , 66 ( 68 % 67 36 68 % 68 % 69 ) 70 , 72 over 72 over 73 70 72 over 78 . 73 70 76 % 74 ( 76 % 75 20 76 % 76 % 77 ) results reveal that almost one - third of midlife and older gay men and lesbians maintain some fear of openly disclosing their sexual orientation . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 reveal 0 ###LEFT-WALL### 6 - 1 results 2 reveal 2 reveal 5 one 3 that 5 one 4 almost 5 one 6 - 14 and 6 - 16 maintain 6 - 25 . 7 third 14 and 8 of 10 and 8 of 14 and 9 midlife 10 and 10 and 12 gay 11 older 12 gay 13 men 14 and 14 and 15 lesbians 14 and 16 maintain 16 maintain 18 fear 17 some 18 fear 18 fear 19 of 19 of 21 disclosing 20 openly 21 disclosing 21 disclosing 24 orientation 22 their 24 orientation 23 sexual 24 orientation along comparable lines with similar proportions , older gay men and lesbians maintain some discomfort in their use of older adult social services , even as the majority reports that they would feel more comfortable accessing lgbt - friendly identified services and programs . 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 24 , 1 along 3 lines 1 along 11 and 2 comparable 3 lines 4 with 6 proportions 4 with 7 , 4 with 11 and 5 similar 6 proportions 8 older 9 gay 9 gay 10 men 10 men 11 and 11 and 12 lesbians 11 and 24 , 13 maintain 15 discomfort 13 maintain 24 , 14 some 15 discomfort 15 discomfort 16 in 15 discomfort 19 of 16 in 18 use 17 their 18 use 19 of 23 services 20 older 23 services 21 adult 23 services 22 social 23 services 24 , 25 even 24 , 29 reports 25 even 26 as 26 as 28 majority 27 the 28 majority 29 reports 30 that 29 reports 36 accessing 30 that 31 they 30 that 33 feel 31 they 32 would 32 would 33 feel 33 feel 35 comfortable 34 more 35 comfortable 36 accessing 37 lgbt 37 lgbt 42 and 38 - 42 and 39 friendly 41 services 40 identified 41 services 41 services 42 and 42 and 43 programs 42 and 44 . in both cases , lesbians reported greater fear and discomfort than did gay men ; older gay men and lesbians reported that they would be less comfortable accessing lgbt - identified services and programs than did younger gay men and lesbians . 0 ###LEFT-WALL### 5 lesbians 0 ###LEFT-WALL### 6 reported 0 ###LEFT-WALL### 15 ; 0 ###LEFT-WALL### 42 . 1 in 3 cases 1 in 4 , 1 in 5 lesbians 2 both 3 cases 5 lesbians 6 reported 6 reported 9 and 6 reported 11 than 7 greater 8 fear 8 fear 9 and 9 and 10 discomfort 11 than 12 did 12 did 14 men 13 gay 14 men 15 ; 40 and 16 older 18 men 17 gay 18 men 18 men 19 and 19 and 20 lesbians 19 and 22 that 19 and 34 programs 19 and 40 and 20 lesbians 21 reported 22 that 23 they 22 that 33 and 23 they 24 would 24 would 25 be 25 be 28 accessing 26 less 28 accessing 27 comfortable 28 accessing 29 lgbt 30 - 29 lgbt 33 and 31 identified 32 services 31 identified 33 and 33 and 34 programs 34 programs 35 than 35 than 36 did 36 did 39 men 37 younger 39 men 38 gay 39 men 40 and 41 lesbians these data support prior research on the apprehension of lgbt elders in accessing care , the crucial role of acceptance , with some suggestions of how social services might better prepare to address these needs . 0 ###LEFT-WALL### 2 data 0 ###LEFT-WALL### 3 support 0 ###LEFT-WALL### 36 . 1 these 2 data 2 data 3 support 3 support 5 research 4 prior 5 research 5 research 6 on 5 research 9 of 6 on 8 apprehension 7 the 8 apprehension 9 of 11 elders 10 lgbt 11 elders 11 elders 12 in 11 elders 25 of 12 in 13 accessing 13 accessing 14 care 13 accessing 22 with 14 care 18 role 15 , 18 role 16 the 18 role 17 crucial 18 role 18 role 19 of 18 role 21 , 19 of 20 acceptance 22 with 24 suggestions 23 some 24 suggestions 25 of 26 how 26 how 27 social 27 social 28 services 28 services 29 might 29 might 31 prepare 30 better 31 prepare 31 prepare 32 to 31 prepare 33 address 32 to 33 address 33 address 35 needs 34 these 35 needs the study examines the frequency and nature of the informal caregiving experience for midlife and older lesbian , gay , bisexual , or transgender ( lgbt ) adults . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 examines 0 ###LEFT-WALL### 18 , 0 ###LEFT-WALL### 29 . 1 the 2 study 2 study 3 examines 3 examines 6 and 4 the 6 and 5 frequency 6 and 6 and 7 nature 6 and 8 of 8 of 15 and 9 the 12 experience 10 informal 12 experience 11 caregiving 12 experience 12 experience 13 for 12 experience 15 and 13 for 14 midlife 15 and 17 lesbian 16 older 17 lesbian 18 , 28 adults 19 gay 23 or 19 gay 28 adults 20 , 23 or 21 bisexual 23 or 22 , 23 or 23 or 24 transgender 23 or 26 lgbt 23 or 27 ) 25 ( 26 lgbt 26 lgbt 27 ) responses from a twin cities metropolitan area lgbt aging needs assessment survey were analyzed for social supports , current caregiving activity and availability of a caregiver . 0 ###LEFT-WALL### 1 responses 0 ###LEFT-WALL### 14 analyzed 0 ###LEFT-WALL### 27 . 1 responses 2 from 1 responses 13 were 2 from 12 survey 3 a 12 survey 4 twin 5 cities 5 cities 6 metropolitan 6 metropolitan 7 area 7 area 8 lgbt 8 lgbt 12 survey 9 aging 11 assessment 10 needs 11 assessment 11 assessment 12 survey 13 were 14 analyzed 14 analyzed 15 for 15 for 22 and 16 social 17 supports 17 supports 18 , 18 , 21 activity 18 , 22 and 19 current 21 activity 20 caregiving 21 activity 22 and 23 availability 22 and 24 of 24 of 26 caregiver 25 a 26 caregiver implications of the findings for enhancing resources to more fully support the 10 % of caregivers that are caring for [non] - kin are discussed . 0 ###LEFT-WALL### 1 implications 0 ###LEFT-WALL### 25 discussed 0 ###LEFT-WALL### 26 . 1 implications 2 of 1 implications 11 support 2 of 4 findings 3 the 4 findings 4 findings 5 for 5 for 6 enhancing 6 enhancing 7 resources 7 resources 8 to 8 to 9 more 10 fully 11 support 11 support 14 % 11 support 20 for 12 the 14 % 13 10 14 % 14 % 15 of 15 of 16 caregivers 16 caregivers 17 that 16 caregivers 18 are 17 that 18 are 18 are 19 caring 20 for 22 - 22 - 23 kin 23 kin 24 are 24 are 25 discussed extensive research on the specific needs and concerns of lesbian [,] gay , bisexual , and transgender ( lgbt ) older adults is lacking . 0 ###LEFT-WALL### 2 research 0 ###LEFT-WALL### 23 is 0 ###LEFT-WALL### 25 . 1 extensive 2 research 2 research 3 on 2 research 9 of 2 research 23 is 3 on 7 and 4 the 6 needs 5 specific 6 needs 6 needs 7 and 7 and 8 concerns 9 of 22 adults 10 lesbian 22 adults 12 gay 16 and 12 gay 22 adults 13 , 16 and 14 bisexual 16 and 15 , 16 and 16 and 17 transgender 16 and 19 lgbt 16 and 20 ) 18 ( 19 lgbt 19 lgbt 20 ) 21 older 22 adults 23 is 24 lacking this article describes the results of both quantitative studies ( i.e [.] , lgbt elders needs assessment scale [ )(and qualitative studies ( i.e [.] , focus groups [and] in [-] depth interviews with lesbian , gay , or bisexual [ lgb ] older adults and lgb grandparents ) that specifically sought to investigate the unique needs and concerns of lgbt elders . 1 this 2 article 2 article 3 describes 3 describes 5 results 4 the 5 results 5 results 6 of 6 of 16 needs 7 both 16 needs 8 quantitative 13 , 8 quantitative 16 needs 9 studies 11 i.e 10 ( 11 i.e 11 i.e 13 , 14 lgbt 15 elders 15 elders 16 needs 16 needs 17 assessment 16 needs 28 groups 17 assessment 22 studies 17 assessment 27 focus 17 assessment 28 groups 18 scale 20 )(and 20 )(and 21 qualitative 20 )(and 22 studies 22 studies 24 i.e 22 studies 27 focus 23 ( 24 i.e 24 i.e 26 , 28 groups 30 in 28 groups 34 with 30 in 33 interviews 32 depth 33 interviews 34 with 46 and 35 lesbian 36 , 36 , 37 gay 36 , 39 or 38 , 39 or 39 or 45 adults 39 or 46 and 40 bisexual 42 lgb 40 bisexual 43 ] 40 bisexual 45 adults 41 [ 42 lgb 42 lgb 43 ] 44 older 45 adults 46 and 48 grandparents 46 and 49 ) 46 and 50 that 46 and 52 sought 47 lgb 48 grandparents 50 that 52 sought 51 specifically 52 sought 52 sought 53 to 52 sought 54 investigate 53 to 54 investigate 54 investigate 58 and 55 the 57 needs 56 unique 57 needs 57 needs 58 and 58 and 59 concerns 58 and 63 . 59 concerns 60 of 60 of 62 elders 61 lgbt 62 elders the results identified 7 areas ( medical/health care , legal , institutional/housing , spiritual , family , mental health , and social ) of concern and the recognition that the needs and concerns of lgbt older adults be addressed across multiple domains , rather than in isolation . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 identified 0 ###LEFT-WALL### 48 . 1 the 2 results 2 results 3 identified 3 identified 5 areas 3 identified 45 than 4 7 5 areas 5 areas 21 and 6 ( 21 and 7 medical/health 8 care 8 care 9 , 9 , 19 health 9 , 21 and 10 legal 12 institutional/housing 10 legal 13 , 10 legal 19 health 11 , 12 institutional/housing 12 institutional/housing 13 , 14 spiritual 16 family 14 spiritual 19 health 15 , 16 family 16 family 17 , 18 mental 19 health 20 , 21 and 21 and 22 social 21 and 23 ) 21 and 24 of 21 and 43 , 24 of 26 and 25 concern 26 and 26 and 28 recognition 26 and 29 that 26 and 39 addressed 27 the 28 recognition 29 that 32 and 29 that 39 addressed 30 the 31 needs 31 needs 32 and 32 and 33 concerns 32 and 34 of 32 and 37 adults 32 and 38 be 32 and 39 addressed 34 of 35 lgbt 36 older 37 adults 37 adults 38 be 39 addressed 40 across 40 across 42 domains 41 multiple 42 domains 44 rather 45 than 45 than 46 in 46 in 47 isolation research on service needs among older adults rarely addresses the special circumstances [of] lesbian , gay , bisexual , and transgender ( lgbt ) individuals , such as their reliance on friend [-] centered social networks or the experience of discrimination from service providers . 0 ###LEFT-WALL### 1 research 0 ###LEFT-WALL### 9 addresses 0 ###LEFT-WALL### 45 . 1 research 2 on 1 research 9 addresses 2 on 4 needs 3 service 4 needs 4 needs 5 among 5 among 7 adults 6 older 7 adults 8 rarely 9 addresses 9 addresses 14 lesbian 9 addresses 28 as 10 the 14 lesbian 11 special 12 circumstances 12 circumstances 14 lesbian 14 lesbian 25 individuals 15 , 25 individuals 16 gay 20 and 16 gay 25 individuals 17 , 20 and 18 bisexual 20 and 19 , 20 and 20 and 21 transgender 20 and 23 lgbt 20 and 24 ) 22 ( 23 lgbt 23 lgbt 24 ) 25 individuals 26 , 27 such 28 as 28 as 30 reliance 29 their 30 reliance 30 reliance 31 on 30 reliance 40 of 31 on 37 or 32 friend 36 networks 34 centered 35 social 35 social 36 networks 36 networks 37 or 37 or 39 experience 38 the 39 experience 40 of 41 discrimination 41 discrimination 42 from 42 from 44 providers 43 service 44 providers limited data suggests that older lgbt adults underutilize health and social services that are important in maintaining independence and quality of life . 0 ###LEFT-WALL### 2 data 0 ###LEFT-WALL### 3 suggests 0 ###LEFT-WALL### 23 . 1 limited 2 data 2 data 3 suggests 3 suggests 4 that 4 that 7 adults 4 that 8 underutilize 5 older 7 adults 6 lgbt 7 adults 8 underutilize 19 and 9 health 10 and 10 and 12 services 10 and 13 that 10 and 14 are 10 and 19 and 11 social 12 services 13 that 14 are 14 are 15 important 15 important 16 in 16 in 18 independence 17 maintaining 18 independence 19 and 20 quality 19 and 21 of 21 of 22 life this study explored the social care networks of this population using a mixed [-] methods approach . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 explored 0 ###LEFT-WALL### 17 . 1 this 2 study 2 study 3 explored 3 explored 7 networks 4 the 7 networks 5 social 6 care 6 care 7 networks 7 networks 8 of 8 of 10 population 9 this 10 population 10 population 11 using 11 using 16 approach 12 a 16 approach 13 mixed 15 methods 15 methods 16 approach data were obtained from 210 lgbt older adults . 0 ###LEFT-WALL### 1 data 0 ###LEFT-WALL### 3 obtained 0 ###LEFT-WALL### 9 . 1 data 2 were 2 were 3 obtained 3 obtained 4 from 4 from 8 adults 5 210 8 adults 6 lgbt 8 adults 7 older 8 adults the average age was 60 years , and 71 % [were] men , 24 % were women , and 5 % were transgender or intersex . 0 ###LEFT-WALL### 3 age 0 ###LEFT-WALL### 4 was 0 ###LEFT-WALL### 26 . 1 the 3 age 2 average 3 age 3 age 4 was 4 was 24 or 5 60 6 years 6 years 8 and 7 , 8 and 8 and 12 men 8 and 13 , 8 and 15 % 8 and 23 transgender 8 and 24 or 9 71 10 % 10 % 12 men 14 24 15 % 15 % 19 and 16 were 17 women 16 were 19 and 18 , 19 and 19 and 23 transgender 20 5 21 % 21 % 22 were 22 were 23 transgender 24 or 25 intersex one - third was black , and 62 % were caucasian . 0 ###LEFT-WALL### 1 one 0 ###LEFT-WALL### 2 - 2 - 3 third 2 - 4 was 2 - 7 and 2 - 12 . 3 third 4 was 4 was 5 black 6 , 7 and 7 and 9 % 7 and 10 were 8 62 9 % 9 % 10 were 10 were 11 caucasian quantitative assessments found high levels of morbidity and friend - centered support networks . 0 ###LEFT-WALL### 2 assessments 0 ###LEFT-WALL### 3 found 0 ###LEFT-WALL### 14 . 1 quantitative 2 assessments 2 assessments 3 found 3 found 4 high 3 found 5 levels 3 found 12 support 5 levels 6 of 5 levels 12 support 6 of 8 and 7 morbidity 8 and 8 and 9 friend 8 and 10 - 8 and 11 centered 12 support 13 networks need for [and] use of services was frequently reported . 0 ###LEFT-WALL### 1 need 0 ###LEFT-WALL### 9 reported 0 ###LEFT-WALL### 10 . 1 need 2 for 1 need 7 was 2 for 4 use 4 use 5 of 5 of 6 services 7 was 9 reported 8 frequently 9 reported content analysis revealed unmet needs for basic supports , including housing , economic supports , and help with entitlements . 0 ###LEFT-WALL### 2 analysis 0 ###LEFT-WALL### 3 revealed 0 ###LEFT-WALL### 20 . 1 content 2 analysis 2 analysis 3 revealed 3 revealed 16 and 3 revealed 18 with 4 unmet 5 needs 5 needs 6 for 5 needs 16 and 6 for 8 supports 7 basic 8 supports 8 supports 10 including 9 , 10 including 10 including 11 housing 10 including 15 , 11 housing 14 supports 12 , 14 supports 13 economic 14 supports 14 supports 15 , 16 and 17 help 18 with 19 entitlements limited opportunities for socialization were strongly expressed , particularly among older lesbians . 0 ###LEFT-WALL### 2 opportunities 0 ###LEFT-WALL### 7 expressed 1 limited 2 opportunities 2 opportunities 3 for 2 opportunities 5 were 3 for 4 socialization 5 were 6 strongly 5 were 7 expressed 7 expressed 10 among 8 , 9 particularly 8 , 10 among 10 among 12 lesbians 10 among 13 . 11 older 12 lesbians implications for senior programs and policies are discussed . 0 ###LEFT-WALL### 1 implications 0 ###LEFT-WALL### 8 discussed 0 ###LEFT-WALL### 9 . 1 implications 2 for 1 implications 7 are 2 for 5 and 3 senior 4 programs 4 programs 5 and 5 and 6 policies 7 are 8 discussed [none] intracellular inclusions seen by the pathologist may have variable significance . 0 ###LEFT-WALL### 3 inclusions 0 ###LEFT-WALL### 9 have 0 ###LEFT-WALL### 12 . 2 intracellular 3 inclusions 3 inclusions 4 seen 3 inclusions 8 may 4 seen 5 by 5 by 7 pathologist 6 the 7 pathologist 8 may 9 have 9 have 11 significance 10 variable 11 significance although they are excellent markers of proteolytic disorders , they can also be due to several other mechanisms . 0 ###LEFT-WALL### 10 they 0 ###LEFT-WALL### 13 be 0 ###LEFT-WALL### 19 . 1 although 2 they 1 although 3 are 1 although 9 , 1 although 10 they 2 they 3 are 3 are 5 markers 4 excellent 5 markers 5 markers 6 of 6 of 8 disorders 7 proteolytic 8 disorders 10 they 11 can 11 can 13 be 12 also 13 be 13 be 15 to 14 due 15 to 15 to 18 mechanisms 16 several 17 other 17 other 18 mechanisms this article examines recent data on the morphology , significance and consequences of aging lipofuscins in the brain and retina , neurofibrillary tangles and lewy bodies , and birbeck granules associated with langerhans histiocytosis . 0 ###LEFT-WALL### 2 article 0 ###LEFT-WALL### 3 examines 0 ###LEFT-WALL### 35 . 1 this 2 article 2 article 3 examines 3 examines 5 data 3 examines 15 lipofuscins 4 recent 5 data 5 data 6 on 5 data 13 of 5 data 15 lipofuscins 6 on 11 and 7 the 8 morphology 8 morphology 9 , 9 , 10 significance 9 , 11 and 11 and 12 consequences 13 of 14 aging 15 lipofuscins 16 in 15 lipofuscins 32 with 16 in 24 and 17 the 18 brain 18 brain 19 and 19 and 20 retina 19 and 21 , 21 , 23 tangles 21 , 24 and 22 neurofibrillary 23 tangles 24 and 25 lewy 24 and 28 and 24 and 31 associated 26 bodies 28 and 27 , 28 and 28 and 30 granules 28 and 31 associated 29 birbeck 30 granules 32 with 34 histiocytosis 33 langerhans 34 histiocytosis some of these disorders involve increased protein production , misfolding and aggregation , and altered intracellular proteolysis , but other cell constituents may also play a role . 0 ###LEFT-WALL### 4 disorders 0 ###LEFT-WALL### 19 but 0 ###LEFT-WALL### 28 . 1 some 2 of 1 some 4 disorders 2 of 4 disorders 3 these 4 disorders 4 disorders 19 but 5 involve 14 and 5 involve 19 but 6 increased 8 production 6 increased 14 and 7 protein 8 production 8 production 11 and 9 , 11 and 10 misfolding 11 and 11 and 12 aggregation 11 and 13 , 14 and 15 altered 14 and 17 proteolysis 15 altered 16 intracellular 18 , 19 but 19 but 25 play 20 other 22 constituents 21 cell 22 constituents 22 constituents 23 may 23 may 25 play 24 also 25 play 25 play 27 role 26 a 27 role proteolytic mechanisms do not appear to be involved in the formation of birbeck granules , which helped to reveal the langerhans origin of histiocytosis x . analyses of intracellular inclusions , together with genetic and epigenetic studies , are highly informative in various degenerative diseases . 0 ###LEFT-WALL### 2 mechanisms 0 ###LEFT-WALL### 5 appear 0 ###LEFT-WALL### 15 , 0 ###LEFT-WALL### 26 . 1 proteolytic 2 mechanisms 2 mechanisms 3 do 3 do 4 not 3 do 5 appear 5 appear 6 to 5 appear 8 involved 6 to 7 be 7 be 8 involved 8 involved 9 in 9 in 11 formation 10 the 11 formation 11 formation 12 of 12 of 14 granules 13 birbeck 14 granules 15 , 16 which 15 , 17 helped 16 which 17 helped 17 helped 18 to 17 helped 19 reveal 18 to 19 reveal 19 reveal 22 origin 20 the 22 origin 21 langerhans 22 origin 22 origin 23 of 23 of 24 histiocytosis 24 histiocytosis 25 x 26 . 27 analyses 26 . 39 are 26 . 46 . 27 analyses 28 of 27 analyses 33 with 27 analyses 39 are 28 of 30 inclusions 29 intracellular 30 inclusions 31 , 33 with 32 together 33 with 33 with 37 studies 33 with 38 , 34 genetic 35 and 35 and 36 epigenetic 35 and 37 studies 39 are 41 informative 40 highly 41 informative 41 informative 42 in 42 in 45 diseases 43 various 45 diseases 44 degenerative 45 diseases as population growth and the aging of the overall population increase demand for health care , policymakers and analysts posit whether sufficient health care providers will be able to meet that demand . 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 11 increase 0 ###LEFT-WALL### 33 . 1 as 2 population 1 as 4 and 3 growth 4 and 4 and 6 aging 4 and 11 increase 5 the 6 aging 6 aging 7 of 7 of 10 population 8 the 10 population 9 overall 10 population 11 increase 12 demand 11 increase 21 whether 12 demand 13 for 12 demand 18 and 12 demand 20 posit 13 for 14 health 15 care 16 , 16 , 17 policymakers 16 , 18 and 18 and 19 analysts 18 and 20 posit 21 whether 25 providers 21 whether 27 be 22 sufficient 23 health 23 health 24 care 24 care 25 providers 25 providers 26 will 26 will 27 be 27 be 28 able 28 able 29 to 29 to 30 meet 30 meet 32 demand 31 that 32 demand some argue there are too few providers already ; others say our current supply - demand problems lie with efficiency . 0 ###LEFT-WALL### 1 some 0 ###LEFT-WALL### 2 argue 0 ###LEFT-WALL### 9 ; 1 some 2 argue 2 argue 3 there 2 argue 4 are 3 there 4 are 4 are 7 providers 4 are 8 already 5 too 6 few 6 few 7 providers 9 ; 10 others 9 ; 11 say 9 ; 15 - 10 others 11 say 11 say 14 supply 12 our 14 supply 13 current 14 supply 15 - 16 demand 15 - 21 . 16 demand 17 problems 16 demand 18 lie 18 lie 19 with 19 with 20 efficiency [but] suppose both are correct ? 0 ###LEFT-WALL### 2 suppose 0 ###LEFT-WALL### 6 ? 2 suppose 3 both 2 suppose 4 are 3 both 4 are 4 are 5 correct perhaps the real challenge is to understand how physician practices are changing in response to market forces such as payment changes , provider distributions , and technology innovations . 0 ###LEFT-WALL### 4 challenge 0 ###LEFT-WALL### 29 . 1 perhaps 4 challenge 2 the 4 challenge 3 real 4 challenge 4 challenge 5 is 5 is 6 to 5 is 7 understand 6 to 7 understand 7 understand 8 how 8 how 10 practices 8 how 11 are 9 physician 10 practices 10 practices 11 are 11 are 12 changing 12 changing 14 response 12 changing 15 to 12 changing 19 as 13 in 14 response 15 to 17 forces 16 market 17 forces 18 such 19 as 19 as 26 and 20 payment 21 changes 21 changes 22 , 22 , 24 distributions 22 , 26 and 23 provider 24 distributions 25 , 26 and 26 and 28 innovations 27 technology 28 innovations this issue brief reviews what is known about evolving practice organizations , professional mixes , information technology support , and the implications of these and other factors for public workforce policies . 0 ###LEFT-WALL### 3 brief 0 ###LEFT-WALL### 4 reviews 0 ###LEFT-WALL### 32 . 1 this 3 brief 2 issue 3 brief 3 brief 4 reviews 4 reviews 5 what 4 reviews 8 about 5 what 6 is 6 is 7 known 8 about 20 and 9 evolving 11 organizations 10 practice 11 organizations 11 organizations 12 , 12 , 14 mixes 12 , 15 , 13 professional 14 mixes 15 , 18 support 15 , 20 and 16 information 17 technology 17 technology 18 support 19 , 20 and 20 and 22 implications 20 and 23 of 21 the 22 implications 23 of 25 and 24 these 25 and 25 and 27 factors 25 and 28 for 26 other 27 factors 28 for 31 policies 29 public 30 workforce 30 workforce 31 policies background : similarities between mice and humans lead to generation of many mouse models of human disease . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 3 similarities 2 : 8 lead 2 : 18 . 3 similarities 4 between 3 similarities 8 lead 4 between 6 and 5 mice 6 and 6 and 7 humans 8 lead 9 to 9 to 10 generation 10 generation 11 of 11 of 14 models 12 many 14 models 13 mouse 14 models 14 models 15 of 15 of 17 disease 16 human 17 disease however , differences between the species often result in mice being unreliable as preclinical models for human disease . 0 ###LEFT-WALL### 3 differences 0 ###LEFT-WALL### 8 result 0 ###LEFT-WALL### 19 . 1 however 2 , 1 however 3 differences 3 differences 4 between 3 differences 8 result 4 between 6 species 5 the 6 species 7 often 8 result 8 result 9 in 9 in 10 mice 10 mice 11 being 11 being 12 unreliable 12 unreliable 13 as 13 as 15 models 14 preclinical 15 models 15 models 16 for 16 for 18 disease 17 human 18 disease one difference that might play a role in lowering the predictivity of mice models to human diseases is age . 0 ###LEFT-WALL### 2 difference 0 ###LEFT-WALL### 18 is 0 ###LEFT-WALL### 20 . 1 one 2 difference 2 difference 3 that 2 difference 4 might 2 difference 18 is 3 that 4 might 4 might 5 play 5 play 7 role 5 play 8 in 6 a 7 role 8 in 9 lowering 9 lowering 11 predictivity 9 lowering 15 to 10 the 11 predictivity 11 predictivity 12 of 12 of 14 models 13 mice 14 models 15 to 17 diseases 16 human 17 diseases 18 is 19 age despite the important role age plays in medicine , it is too often considered only casually when considering mouse models . 0 ###LEFT-WALL### 10 it 0 ###LEFT-WALL### 14 considered 0 ###LEFT-WALL### 21 . 1 despite 6 plays 1 despite 9 , 1 despite 10 it 2 the 6 plays 3 important 4 role 4 role 6 plays 5 age 6 plays 6 plays 7 in 7 in 8 medicine 10 it 11 is 11 is 14 considered 12 too 13 often 13 often 14 considered 14 considered 15 only 14 considered 16 casually 14 considered 17 when 17 when 18 considering 18 considering 20 models 19 mouse 20 models methods : we developed the mouse - age phenotype knowledgebase , which holds knowledge about age - related phenotypic patterns in mice . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 3 we 2 : 4 developed 2 : 18 related 2 : 23 . 3 we 4 developed 4 developed 6 mouse 5 the 6 mouse 6 mouse 10 knowledgebase 6 mouse 12 which 7 - 10 knowledgebase 8 age 9 phenotype 9 phenotype 10 knowledgebase 10 knowledgebase 11 , 11 , 12 which 12 which 13 holds 12 which 17 - 13 holds 14 knowledge 13 holds 15 about 15 about 16 age 17 - 18 related 18 related 20 patterns 18 related 21 in 19 phenotypic 20 patterns 21 in 22 mice the knowledgebase was extensively populated with literature - derived data using text mining techniques . 0 ###LEFT-WALL### 2 knowledgebase 0 ###LEFT-WALL### 5 populated 0 ###LEFT-WALL### 8 - 0 ###LEFT-WALL### 15 . 1 the 2 knowledgebase 2 knowledgebase 3 was 3 was 5 populated 4 extensively 5 populated 5 populated 6 with 6 with 7 literature 8 - 10 data 9 derived 10 data 10 data 11 using 11 using 12 text 12 text 13 mining 13 mining 14 techniques we then mapped between ages in humans and mice by comparing the age distribution pattern for 887 diseases in both species . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 mapped 0 ###LEFT-WALL### 22 . 1 we 3 mapped 2 then 3 mapped 3 mapped 4 between 3 mapped 6 in 3 mapped 10 by 3 mapped 15 pattern 3 mapped 19 in 4 between 5 ages 6 in 8 and 7 humans 8 and 8 and 9 mice 10 by 11 comparing 12 the 15 pattern 13 age 15 pattern 14 distribution 15 pattern 15 pattern 16 for 16 for 18 diseases 17 887 18 diseases 19 in 21 species 20 both 21 species results : the knowledgebase was populated with over 9800 instances generated by a text - mining pipeline . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 4 knowledgebase 2 : 6 populated 2 : 15 - 3 the 4 knowledgebase 4 knowledgebase 5 was 5 was 6 populated 6 populated 7 with 7 with 10 instances 8 over 9 9800 9 9800 10 instances 10 instances 11 generated 11 generated 12 by 12 by 14 text 13 a 14 text 15 - 17 pipeline 15 - 18 . 16 mining 17 pipeline the quality of the data was manually evaluated , and was found to be of high accuracy ( estimated precision >86 [%] ) . 0 ###LEFT-WALL### 2 quality 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 24 . 1 the 2 quality 2 quality 3 of 2 quality 10 and 3 of 5 data 4 the 5 data 6 was 8 evaluated 6 was 10 and 7 manually 8 evaluated 9 , 10 and 10 and 11 was 11 was 12 found 12 found 13 to 13 to 14 be 14 be 15 of 15 of 17 accuracy 16 high 17 accuracy 17 accuracy 21 >86 18 ( 21 >86 19 estimated 20 precision 20 precision 21 >86 21 >86 23 ) furthermore , grouping together diseases that share similar age patterns in mice resulted in clusters that mirror actual biomedical knowledge . 0 ###LEFT-WALL### 3 grouping 0 ###LEFT-WALL### 13 resulted 0 ###LEFT-WALL### 21 . 1 furthermore 2 , 1 furthermore 3 grouping 3 grouping 4 together 3 grouping 5 diseases 3 grouping 13 resulted 5 diseases 6 that 5 diseases 7 share 6 that 7 share 7 share 10 patterns 7 share 11 in 8 similar 9 age 9 age 10 patterns 11 in 12 mice 13 resulted 14 in 14 in 15 clusters 15 clusters 16 that 15 clusters 17 mirror 16 that 17 mirror 17 mirror 20 knowledge 18 actual 20 knowledge 19 biomedical 20 knowledge using these data , we matched age distribution patterns in mice and in humans , allowing for age differences by shifting either of the patterns . 0 ###LEFT-WALL### 5 we 0 ###LEFT-WALL### 6 matched 1 using 3 data 1 using 4 , 1 using 5 we 2 these 3 data 5 we 6 matched 6 matched 9 patterns 7 age 9 patterns 8 distribution 9 patterns 9 patterns 12 and 10 in 11 mice 10 in 12 and 12 and 13 in 13 in 14 humans 14 humans 17 for 15 , 17 for 16 allowing 17 for 17 for 19 differences 17 for 20 by 17 for 26 . 18 age 19 differences 20 by 21 shifting 21 shifting 22 either 22 either 23 of 23 of 25 patterns 24 the 25 patterns high [correlation] [(] [r] ( 2 )>0.5 ) was found for 223 diseases . 0 ###LEFT-WALL### 1 high 0 ###LEFT-WALL### 10 found 0 ###LEFT-WALL### 14 . 1 high 7 )>0.5 1 high 9 was 5 ( 7 )>0.5 6 2 7 )>0.5 7 )>0.5 8 ) 9 was 10 found 10 found 11 for 11 for 13 diseases 12 223 13 diseases the results clearly indicate a difference in the age mapping between different diseases : age 30 years in human [is] mapped [to] 120 days in mice for leukemia , but to 295 days for anemia . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 4 indicate 0 ###LEFT-WALL### 14 : 0 ###LEFT-WALL### 36 . 1 the 2 results 2 results 4 indicate 3 clearly 4 indicate 4 indicate 6 difference 4 indicate 7 in 5 a 6 difference 7 in 10 mapping 8 the 10 mapping 9 age 10 mapping 10 mapping 11 between 11 between 13 diseases 12 different 13 diseases 14 : 15 age 15 age 16 30 15 age 17 years 15 age 18 in 18 in 24 days 19 human 21 mapped 21 mapped 24 days 23 120 24 days 24 days 30 but 24 days 34 for 25 in 26 mice 25 in 30 but 26 mice 27 for 27 for 28 leukemia 29 , 30 but 30 but 31 to 31 to 33 days 32 295 33 days 34 for 35 anemia based on these results we generated [a] mice [-] to - human age [map] [which] is publicly available . 0 ###LEFT-WALL### 13 age 0 ###LEFT-WALL### 16 is 0 ###LEFT-WALL### 19 . 1 based 2 on 1 based 11 - 1 based 13 age 2 on 4 results 3 these 4 results 4 results 5 we 4 results 10 to 5 we 6 generated 6 generated 8 mice 6 generated 10 to 12 human 13 age 13 age 16 is 16 is 17 publicly 16 is 18 available conclusions : we present here the development of the mouse - apk , its population with literature - derived data and its use to map ages in mice and human for 223 diseases . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 25 map 0 ###LEFT-WALL### 34 . 2 : 3 we 2 : 4 present 2 : 11 - 3 we 4 present 4 present 5 here 4 present 7 development 6 the 7 development 7 development 8 of 8 of 10 mouse 9 the 10 mouse 11 - 12 apk 11 - 19 derived 12 apk 15 population 12 apk 19 derived 13 , 15 population 14 its 15 population 15 population 16 with 15 population 18 - 16 with 17 literature 19 derived 21 and 19 derived 24 to 20 data 21 and 21 and 23 use 22 its 23 use 24 to 25 map 25 map 26 ages 25 map 27 in 27 in 29 and 28 mice 29 and 29 and 30 human 29 and 31 for 31 for 33 diseases 32 223 33 diseases these results present a further step made to bridging the gap between humans and mice in biomedical research . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 present 0 ###LEFT-WALL### 19 . 1 these 2 results 2 results 3 present 3 present 6 step 4 a 6 step 5 further 6 step 6 step 7 made 7 made 8 to 8 to 9 bridging 9 bridging 11 gap 9 bridging 12 between 9 bridging 16 in 10 the 11 gap 12 between 14 and 13 humans 14 and 14 and 15 mice 16 in 18 research 17 biomedical 18 research background : it is usually possible to identify the sex of a pre - pubertal child from their voice , despite the absence of sex differences in fundamental frequency at these ages . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 3 it 2 : 4 is 2 : 33 . 3 it 4 is 4 is 5 usually 4 is 6 possible 5 usually 6 possible 6 possible 7 to 6 possible 8 identify 7 to 8 identify 8 identify 10 sex 8 identify 21 despite 8 identify 27 in 8 identify 30 at 9 the 10 sex 10 sex 11 of 11 of 13 pre 12 a 13 pre 13 pre 16 child 14 - 16 child 15 pubertal 16 child 16 child 17 from 16 child 20 , 17 from 19 voice 18 their 19 voice 21 despite 23 absence 22 the 23 absence 23 absence 24 of 24 of 26 differences 25 sex 26 differences 27 in 29 frequency 28 fundamental 29 frequency 30 at 32 ages 31 these 32 ages while it has been suggested that the overall spacing between formants ( formant frequency spacing -- δf ) is a key component of the expression and perception of sex in children 's voices , the effect of its continuous variation on sex and gender attribution has not yet been investigated . 0 ###LEFT-WALL### 6 that 0 ###LEFT-WALL### 32 's 0 ###LEFT-WALL### 34 , 0 ###LEFT-WALL### 51 . 1 while 2 it 1 while 5 suggested 1 while 6 that 2 it 3 has 3 has 4 been 4 been 5 suggested 6 that 8 overall 6 that 19 is 6 that 32 's 7 the 8 overall 8 overall 9 spacing 8 overall 10 between 8 overall 14 frequency 8 overall 17 δf 8 overall 19 is 10 between 11 formants 12 ( 14 frequency 13 formant 14 frequency 14 frequency 15 spacing 14 frequency 16 -- 16 -- 17 δf 17 δf 18 ) 19 is 22 component 20 a 22 component 21 key 22 component 22 component 23 of 22 component 30 in 23 of 26 and 24 the 25 expression 25 expression 26 and 26 and 27 perception 26 and 28 of 28 of 29 sex 30 in 31 children 32 's 33 voices 34 , 36 effect 34 , 49 been 35 the 36 effect 36 effect 37 of 36 effect 46 has 37 of 40 variation 38 its 40 variation 39 continuous 40 variation 40 variation 41 on 41 on 43 and 42 sex 43 and 43 and 45 attribution 44 gender 45 attribution 46 has 47 not 46 has 49 been 48 yet 49 been 49 been 50 investigated methodology/principal findings : in the present study we manipulated voice δf of eight year olds ( two boys and two girls ) along continua covering the observed variation of this parameter in pre - pubertal voices , and assessed the effect of this variation on adult ratings of speakers ' sex and gender in two separate experiments . 0 ###LEFT-WALL### 2 findings 0 ###LEFT-WALL### 3 : 0 ###LEFT-WALL### 58 . 1 methodology/principal 2 findings 3 : 38 and 4 in 7 study 4 in 38 and 5 the 7 study 6 present 7 study 7 study 8 we 7 study 9 manipulated 8 we 9 manipulated 10 voice 11 δf 10 voice 23 along 10 voice 32 in 10 voice 38 and 11 δf 12 of 12 of 15 olds 13 eight 14 year 14 year 15 olds 15 olds 19 and 16 ( 19 and 17 two 18 boys 18 boys 19 and 19 and 21 girls 19 and 22 ) 20 two 21 girls 23 along 24 continua 24 continua 25 covering 24 continua 29 of 25 covering 28 variation 26 the 28 variation 27 observed 28 variation 29 of 31 parameter 30 this 31 parameter 32 in 33 pre 33 pre 36 voices 34 - 36 voices 35 pubertal 36 voices 36 voices 37 , 38 and 39 assessed 39 assessed 41 effect 39 assessed 45 on 39 assessed 54 in 40 the 41 effect 41 effect 42 of 42 of 44 variation 43 this 44 variation 45 on 52 and 46 adult 47 ratings 47 ratings 48 of 47 ratings 52 and 48 of 51 sex 49 speakers 50 ' 50 ' 51 sex 52 and 53 gender 54 in 57 experiments 55 two 57 experiments 56 separate 57 experiments in the first experiment ( sex identification ) adults were asked to categorise the voice as either male or female . 0 ###LEFT-WALL### 9 adults 0 ###LEFT-WALL### 11 asked 0 ###LEFT-WALL### 21 . 1 in 4 experiment 1 in 9 adults 2 the 3 first 2 the 4 experiment 4 experiment 7 identification 5 ( 7 identification 6 sex 7 identification 7 identification 8 ) 9 adults 10 were 10 were 11 asked 11 asked 12 to 11 asked 13 categorise 12 to 13 categorise 13 categorise 15 voice 13 categorise 16 as 14 the 15 voice 16 as 19 or 17 either 18 male 18 male 19 or 19 or 20 female the resulting identification function exhibited a gradual slope from male [to] female voice categories . 0 ###LEFT-WALL### 4 function 0 ###LEFT-WALL### 5 exhibited 0 ###LEFT-WALL### 15 . 1 the 4 function 2 resulting 3 identification 3 identification 4 function 4 function 5 exhibited 5 exhibited 8 slope 5 exhibited 9 from 6 a 7 gradual 6 a 8 slope 7 gradual 8 slope 9 from 14 categories 10 male 12 female 12 female 13 voice 13 voice 14 categories in the second experiment ( gender rating ) , adults rated the voices on a [continuum] [from] ["] masculine boy " [to] ["] feminine girl " , gradually decreasing their masculinity ratings as δf increased . 0 ###LEFT-WALL### 10 adults 0 ###LEFT-WALL### 11 rated 0 ###LEFT-WALL### 27 , 0 ###LEFT-WALL### 36 . 1 in 4 experiment 1 in 9 , 1 in 10 adults 2 the 3 second 2 the 4 experiment 4 experiment 6 gender 5 ( 6 gender 6 gender 7 rating 6 gender 8 ) 10 adults 11 rated 11 rated 13 voices 11 rated 14 on 12 the 13 voices 14 on 25 girl 15 a 25 girl 19 masculine 20 boy 20 boy 21 " 20 boy 25 girl 24 feminine 25 girl 25 girl 26 " 27 , 29 decreasing 27 , 35 increased 28 gradually 29 decreasing 29 decreasing 32 ratings 29 decreasing 33 as 29 decreasing 35 increased 30 their 32 ratings 31 masculinity 32 ratings 33 as 34 δf conclusions/significance : these results indicate that [the] role of δf in voice gender perception , which has been reported in adult voices , extends to pre - pubertal children 's voices [:] variation in δf [not] only affects the perceived sex , but also [the] perceived masculinity or femininity of the speaker . 0 ###LEFT-WALL### 1 conclusions/significance 0 ###LEFT-WALL### 2 : 2 : 4 results 2 : 5 indicate 3 these 4 results 4 results 5 indicate 5 indicate 8 role 5 indicate 11 in 6 that 8 role 8 role 9 of 9 of 10 δf 11 in 14 perception 12 voice 13 gender 13 gender 14 perception 14 perception 16 which 15 , 16 which 16 which 23 , 17 has 18 been 17 has 23 , 18 been 19 reported 19 reported 20 in 20 in 22 voices 21 adult 22 voices 23 , 24 extends 24 extends 25 to 24 extends 31 voices 25 to 30 's 26 pre 27 - 26 pre 29 children 28 pubertal 29 children 29 children 30 's 31 voices 33 variation 31 voices 38 affects 31 voices 43 but 33 variation 34 in 33 variation 38 affects 34 in 35 δf 37 only 38 affects 38 affects 41 sex 39 the 41 sex 40 perceived 41 sex 42 , 43 but 43 but 44 also 43 but 48 or 43 but 53 . 46 perceived 47 masculinity 47 masculinity 48 or 48 or 49 femininity 48 or 50 of 50 of 52 speaker 51 the 52 speaker we discuss the implications of these observations for the expression and perception of gender in children 's voices given the absence of anatomical dimorphism in overall vocal tract length before puberty . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 discuss 0 ###LEFT-WALL### 32 . 1 we 2 discuss 2 discuss 4 implications 2 discuss 8 for 2 discuss 15 in 2 discuss 30 before 3 the 4 implications 4 implications 5 of 5 of 7 observations 6 these 7 observations 8 for 11 and 9 the 10 expression 10 expression 11 and 11 and 12 perception 11 and 13 of 13 of 14 gender 15 in 18 voices 16 children 17 's 17 's 18 voices 18 voices 19 given 18 voices 22 of 19 given 21 absence 20 the 21 absence 22 of 24 dimorphism 23 anatomical 24 dimorphism 24 dimorphism 25 in 25 in 29 length 26 overall 27 vocal 27 vocal 29 length 28 tract 29 length 30 before 31 puberty background : mesenchymal stem cells ( mscs ) have been considered as ideal cells for the treatment of a variety of diseases . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 23 . 2 : 5 cells 2 : 11 considered 3 mesenchymal 4 stem 4 stem 5 cells 5 cells 7 mscs 5 cells 9 have 6 ( 7 mscs 7 mscs 8 ) 9 have 10 been 10 been 11 considered 11 considered 12 as 12 as 14 cells 13 ideal 14 cells 14 cells 15 for 14 cells 18 of 15 for 17 treatment 16 the 17 treatment 18 of 20 variety 19 a 20 variety 20 variety 21 of 21 of 22 diseases however , aging and spontaneous differentiation [of] mscs during culture expansion dampen their effectiveness . 0 ###LEFT-WALL### 8 mscs 0 ###LEFT-WALL### 12 dampen 0 ###LEFT-WALL### 15 . 1 however 2 , 1 however 8 mscs 3 aging 4 and 4 and 5 spontaneous 4 and 6 differentiation 6 differentiation 8 mscs 8 mscs 9 during 8 mscs 12 dampen 9 during 11 expansion 10 culture 11 expansion 12 dampen 14 effectiveness 13 their 14 effectiveness previous studies suggest that ex vivo aging of mscs is largely caused by epigenetic changes [particularly] a decline of histone h3 acetylation levels in promoter regions of pluripotent genes due to inappropriate growth [environment] . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 3 suggest 0 ###LEFT-WALL### 35 . 1 previous 2 studies 2 studies 3 suggest 3 suggest 6 vivo 3 suggest 7 aging 3 suggest 23 levels 4 that 6 vivo 5 ex 6 vivo 7 aging 8 of 7 aging 10 is 8 of 9 mscs 10 is 12 caused 11 largely 12 caused 12 caused 13 by 13 by 15 changes 14 epigenetic 15 changes 15 changes 18 decline 15 changes 23 levels 17 a 18 decline 18 decline 19 of 18 decline 23 levels 19 of 22 acetylation 20 histone 22 acetylation 21 h3 22 acetylation 23 levels 24 in 23 levels 31 to 24 in 26 regions 25 promoter 26 regions 26 regions 27 of 27 of 29 genes 28 pluripotent 29 genes 30 due 31 to 31 to 33 growth 32 inappropriate 33 growth methodology/principal findings : in this study , we examined whether histone deacetylase inhibitor trichostatin a ( tsa ) could suppress the histone h3 deacetylation thus maintaining the primitive property of mscs . 0 ###LEFT-WALL### 2 findings 0 ###LEFT-WALL### 3 : 0 ###LEFT-WALL### 7 , 0 ###LEFT-WALL### 32 . 1 methodology/principal 2 findings 2 findings 3 : 3 : 4 in 4 in 6 study 5 this 6 study 7 , 8 we 7 , 9 examined 8 we 9 examined 9 examined 10 whether 10 whether 14 trichostatin 10 whether 20 suppress 11 histone 12 deacetylase 12 deacetylase 14 trichostatin 13 inhibitor 14 trichostatin 14 trichostatin 15 a 14 trichostatin 17 tsa 14 trichostatin 19 could 16 ( 17 tsa 17 tsa 18 ) 19 could 20 suppress 20 suppress 24 deacetylation 21 the 24 deacetylation 22 histone 24 deacetylation 23 h3 24 deacetylation 24 deacetylation 26 maintaining 24 deacetylation 30 of 25 thus 26 maintaining 26 maintaining 29 property 27 the 29 property 28 primitive 29 property 30 of 31 mscs we found that in regular adherent culture , human mscs became [flatter] [and] larger upon successive passaging [,] while [the] [expression] of pluripotent genes such as oct4 , sox2 , nanog , rex - 1 , cd133 and tert decreased markedly . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 found 0 ###LEFT-WALL### 8 , 0 ###LEFT-WALL### 11 became 1 we 2 found 2 found 3 that 2 found 4 in 4 in 7 culture 5 regular 7 culture 6 adherent 7 culture 8 , 10 mscs 9 human 10 mscs 10 mscs 11 became 11 became 14 larger 14 larger 15 upon 14 larger 19 while 14 larger 26 as 15 upon 17 passaging 16 successive 17 passaging 19 while 22 of 22 of 24 genes 23 pluripotent 24 genes 25 such 26 as 26 as 27 oct4 27 oct4 29 sox2 27 oct4 33 rex 27 oct4 35 1 28 , 29 sox2 29 sox2 31 nanog 29 sox2 32 , 30 , 31 nanog 31 nanog 32 , 32 , 33 rex 33 rex 34 - 34 - 35 1 35 1 38 and 35 1 42 . 36 , 38 and 37 cd133 38 and 38 and 39 tert 38 and 40 decreased 38 and 42 . 40 decreased 41 markedly administration of low concentrations of tsa in culture significantly suppressed the morphological changes in mscs otherwise occurred during culture expansion , increased their proliferation while retaining their cell contact growth inhibition property and multipotent differentiation ability . 0 ###LEFT-WALL### 13 changes 0 ###LEFT-WALL### 21 , 0 ###LEFT-WALL### 37 . 1 administration 13 changes 2 of 4 concentrations 2 of 13 changes 3 low 4 concentrations 4 concentrations 5 of 5 of 6 tsa 6 tsa 7 in 6 tsa 10 suppressed 7 in 8 culture 9 significantly 10 suppressed 11 the 13 changes 12 morphological 13 changes 13 changes 14 in 13 changes 21 , 14 in 15 mscs 16 otherwise 17 occurred 17 occurred 18 during 17 occurred 21 , 18 during 20 expansion 19 culture 20 expansion 21 , 22 increased 22 increased 24 proliferation 22 increased 25 while 23 their 24 proliferation 25 while 26 retaining 26 retaining 33 and 27 their 32 property 28 cell 30 growth 29 contact 30 growth 30 growth 32 property 31 inhibition 32 property 32 property 33 and 33 and 36 ability 34 multipotent 35 differentiation 35 differentiation 36 ability moreover , tsa stabilized the expression of the [above] pluripotent genes and histone h3 acetylation levels in k9 and k14 in promoter regions of oct4 , sox2 and tert . 0 ###LEFT-WALL### 3 tsa 0 ###LEFT-WALL### 4 stabilized 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 30 . 1 moreover 2 , 1 moreover 3 tsa 3 tsa 4 stabilized 4 stabilized 6 expression 5 the 6 expression 6 expression 7 of 7 of 11 genes 8 the 11 genes 10 pluripotent 11 genes 12 and 15 acetylation 12 and 16 levels 13 histone 15 acetylation 14 h3 15 acetylation 15 acetylation 16 levels 16 levels 17 in 16 levels 20 k14 16 levels 21 in 18 k9 19 and 19 and 20 k14 21 in 28 and 22 promoter 23 regions 23 regions 24 of 23 regions 26 , 24 of 25 oct4 26 , 27 sox2 26 , 28 and 28 and 29 tert conclusions/significance : our results suggest that tsa may serve as an effective culture additive to maintain the primitive feature of mscs during culture expansion . 0 ###LEFT-WALL### 1 conclusions/significance 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 16 maintain 0 ###LEFT-WALL### 25 . 2 : 4 results 2 : 5 suggest 3 our 4 results 4 results 5 suggest 5 suggest 6 that 6 that 7 tsa 6 that 9 serve 7 tsa 8 may 8 may 9 serve 9 serve 10 as 9 serve 15 to 10 as 14 additive 11 an 12 effective 11 an 14 additive 12 effective 13 culture 13 culture 14 additive 15 to 16 maintain 16 maintain 19 feature 17 the 19 feature 18 primitive 19 feature 19 feature 20 of 20 of 21 mscs 21 mscs 22 during 22 during 24 expansion 23 culture 24 expansion background : rimmed vacuoles ( rvs ) are round - oval cytoplasmic inclusions , detected in muscle cells of patients with myopathies , such as inclusion body myositis ( ibm ) and distal myopathy with rvs ( dmrv ) . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 40 . 2 : 4 vacuoles 2 : 8 are 3 rimmed 4 vacuoles 4 vacuoles 6 rvs 4 vacuoles 8 are 5 ( 6 rvs 6 rvs 7 ) 8 are 13 inclusions 8 are 15 detected 9 round 10 - 9 round 13 inclusions 11 oval 13 inclusions 12 cytoplasmic 13 inclusions 14 , 15 detected 15 detected 16 in 15 detected 35 with 15 detected 39 ) 16 in 32 and 17 muscle 18 cells 18 cells 19 of 18 cells 32 and 19 of 20 patients 20 patients 21 with 20 patients 25 as 21 with 22 myopathies 23 , 25 as 24 such 25 as 25 as 28 myositis 25 as 31 ) 26 inclusion 28 myositis 27 body 28 myositis 28 myositis 30 ibm 29 ( 30 ibm 30 ibm 31 ) 32 and 34 myopathy 33 distal 34 myopathy 35 with 38 dmrv 36 rvs 38 dmrv 37 ( 38 dmrv 38 dmrv 39 ) granulovacuolar [degeneration] ( gvd ) bodies are spherical vacuoles containing argentophilic and hematoxyphilic granules , and [are] one of the pathological hallmarks commonly found in hippocampal pyramidal neurons of patients with aging - related neurodegenerative diseases , such as alzheimer 's disease and parkinson 's disease . 0 ###LEFT-WALL### 6 bodies 0 ###LEFT-WALL### 24 found 0 ###LEFT-WALL### 47 . 1 granulovacuolar 4 gvd 3 ( 4 gvd 4 gvd 5 ) 4 gvd 6 bodies 6 bodies 7 are 7 are 9 vacuoles 8 spherical 9 vacuoles 9 vacuoles 10 containing 9 vacuoles 16 and 9 vacuoles 24 found 10 containing 12 and 11 argentophilic 12 and 12 and 13 hematoxyphilic 14 granules 16 and 15 , 16 and 16 and 18 one 16 and 19 of 16 and 24 found 19 of 22 hallmarks 20 the 22 hallmarks 21 pathological 22 hallmarks 23 commonly 24 found 24 found 25 in 24 found 39 as 25 in 28 neurons 26 hippocampal 28 neurons 27 pyramidal 28 neurons 28 neurons 29 of 29 of 30 patients 30 patients 31 with 30 patients 36 diseases 31 with 32 aging 33 - 36 diseases 34 related 36 diseases 35 neurodegenerative 36 diseases 36 diseases 37 , 38 such 39 as 39 as 43 and 40 alzheimer 41 's 41 's 42 disease 42 disease 43 and 43 and 46 disease 44 parkinson 45 's 45 's 46 disease these diseases are common in the elderly and [share] some pathological features . 0 ###LEFT-WALL### 2 diseases 0 ###LEFT-WALL### 3 are 0 ###LEFT-WALL### 13 . 1 these 2 diseases 2 diseases 3 are 3 are 4 common 4 common 5 in 5 in 8 and 6 the 7 elderly 7 elderly 8 and 8 and 12 features 10 some 12 features 11 pathological 12 features therefore , we hypothesized that mechanisms of vacuolar formation in rvs and gvd bodies are common despite their role in two differing pathologies . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 hypothesized 0 ###LEFT-WALL### 24 . 1 therefore 2 , 1 therefore 3 we 3 we 4 hypothesized 4 hypothesized 5 that 5 that 12 and 5 that 15 are 6 mechanisms 7 of 6 mechanisms 12 and 7 of 9 formation 8 vacuolar 9 formation 9 formation 10 in 10 in 11 rvs 12 and 14 bodies 12 and 15 are 13 gvd 14 bodies 15 are 16 common 16 common 17 despite 16 common 20 in 17 despite 19 role 18 their 19 role 20 in 23 pathologies 21 two 23 pathologies 22 differing 23 pathologies we explored the components of rvs by immunohistochemistry , using antibodies for gvd markers . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 explored 1 we 2 explored 2 explored 4 components 2 explored 7 by 3 the 4 components 4 components 5 of 5 of 6 rvs 7 by 8 immunohistochemistry 8 immunohistochemistry 10 using 9 , 10 using 10 using 11 antibodies 10 using 15 . 11 antibodies 12 for 12 for 14 markers 13 gvd 14 markers methods : subjects included one ad case , eight cases of sporadic ibm , and three cases of dmrv . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 20 . 2 : 3 subjects 2 : 4 included 2 : 8 , 3 subjects 4 included 4 included 7 case 5 one 7 case 6 ad 7 case 8 , 15 and 9 eight 10 cases 10 cases 11 of 10 cases 15 and 11 of 13 ibm 12 sporadic 13 ibm 14 , 15 and 15 and 17 cases 15 and 18 of 16 three 17 cases 18 of 19 dmrv we compared immunoreactivity and staining patterns for gvd markers . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 compared 0 ###LEFT-WALL### 10 . 1 we 2 compared 2 compared 4 and 3 immunoreactivity 4 and 4 and 6 patterns 4 and 7 for 5 staining 6 patterns 7 for 9 markers 8 gvd 9 markers furthermore , we performed double staining of each gvd marker with ptdp43 to verify the co - localization . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 performed 0 ###LEFT-WALL### 19 . 1 furthermore 2 , 1 furthermore 3 we 3 we 4 performed 4 performed 6 staining 4 performed 11 with 4 performed 13 to 5 double 6 staining 6 staining 7 of 7 of 10 marker 8 each 10 marker 9 gvd 10 marker 11 with 12 ptdp43 13 to 14 verify 14 verify 18 localization 15 the 18 localization 16 co 17 - 16 co 18 localization results : gvd markers , including lipid raft - associated proteins and tau kinases , were detected in rvs . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 5 , 0 ###LEFT-WALL### 20 . 1 results 2 : 2 : 4 markers 3 gvd 4 markers 5 , 8 raft 5 , 9 - 6 including 8 raft 7 lipid 8 raft 9 - 15 , 10 associated 12 and 10 associated 15 , 11 proteins 12 and 12 and 14 kinases 13 tau 14 kinases 15 , 16 were 16 were 17 detected 17 detected 18 in 18 in 19 rvs chmp2b , ptdp43 , caspase 3 , lrrk2 , annexin 2 and flotillin - 1 were detected on the rim and were diffusely distributed in the cytoplasm of rv - positive fibers . 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 14 - 0 ###LEFT-WALL### 33 . 1 chmp2b 2 , 2 , 10 annexin 2 , 12 and 3 ptdp43 5 caspase 3 ptdp43 9 , 3 ptdp43 10 annexin 4 , 5 caspase 5 caspase 6 3 5 caspase 8 lrrk2 5 caspase 9 , 7 , 8 lrrk2 8 lrrk2 9 , 10 annexin 11 2 12 and 13 flotillin 14 - 15 1 14 - 21 and 15 1 21 and 16 were 17 detected 16 were 21 and 17 detected 18 on 18 on 20 rim 19 the 20 rim 21 and 22 were 21 and 32 fibers 22 were 24 distributed 23 diffusely 24 distributed 24 distributed 25 in 24 distributed 30 - 24 distributed 31 positive 25 in 27 cytoplasm 26 the 27 cytoplasm 27 cytoplasm 28 of 28 of 29 rv cdk5 , ck1δ and jnk were detected only on the rim . 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 7 detected 0 ###LEFT-WALL### 12 . 1 cdk5 2 , 2 , 3 ck1δ 2 , 4 and 4 and 5 jnk 4 and 6 were 6 were 7 detected 7 detected 8 only 8 only 9 on 9 on 11 rim 10 the 11 rim in double staining experiments , all gvd markers colocalized with ptdp43 in rvs . 0 ###LEFT-WALL### 8 markers 0 ###LEFT-WALL### 9 colocalized 0 ###LEFT-WALL### 14 . 1 in 4 experiments 1 in 5 , 1 in 8 markers 2 double 3 staining 3 staining 4 experiments 6 all 8 markers 7 gvd 8 markers 8 markers 9 colocalized 9 colocalized 10 with 9 colocalized 12 in 10 with 11 ptdp43 12 in 13 rvs conclusions : these results suggest that rvs of muscle cells and gvd bodies of neurons share a number of molecules , such as raft [-] related proteins and tau - modifying proteins . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 33 . 2 : 4 results 2 : 5 suggest 3 these 4 results 4 results 5 suggest 5 suggest 6 that 6 that 7 rvs 6 that 16 share 7 rvs 8 of 7 rvs 16 share 8 of 11 and 9 muscle 10 cells 10 cells 11 and 11 and 13 bodies 11 and 14 of 12 gvd 13 bodies 14 of 15 neurons 16 share 18 number 17 a 18 number 18 number 19 of 18 number 31 modifying 19 of 20 molecules 20 molecules 23 as 21 , 23 as 22 such 23 as 23 as 28 and 23 as 30 - 24 raft 27 proteins 26 related 27 proteins 27 proteins 28 and 28 and 29 tau 31 modifying 32 proteins zebrafish ( danio rerio ) [are] used extensively in sleep research ; both to further understanding of sleep in general [and] also as a model of human sleep . 0 ###LEFT-WALL### 1 zebrafish 0 ###LEFT-WALL### 7 used 0 ###LEFT-WALL### 12 ; 0 ###LEFT-WALL### 29 . 1 zebrafish 4 rerio 1 zebrafish 7 used 2 ( 4 rerio 3 danio 4 rerio 4 rerio 5 ) 7 used 8 extensively 7 used 9 in 7 used 11 research 9 in 10 sleep 12 ; 14 to 12 ; 15 further 13 both 14 to 14 to 15 further 15 further 16 understanding 15 further 22 also 15 further 23 as 16 understanding 17 of 17 of 18 sleep 18 sleep 20 general 19 in 20 general 23 as 25 model 24 a 25 model 25 model 26 of 26 of 28 sleep 27 human 28 sleep to date , sleep studies have been performed in larval and adult zebrafish but no efforts have been made to document the ontogeny of zebrafish sleep - wake cycles . 0 ###LEFT-WALL### 1 to 0 ###LEFT-WALL### 3 , 0 ###LEFT-WALL### 27 - 0 ###LEFT-WALL### 30 . 1 to 3 , 2 date 3 , 3 , 14 but 4 sleep 5 studies 5 studies 6 have 6 have 7 been 7 been 14 but 8 performed 9 in 8 performed 14 but 9 in 11 and 10 larval 11 and 11 and 13 zebrafish 12 adult 13 zebrafish 14 but 21 document 15 no 16 efforts 16 efforts 17 have 17 have 18 been 18 been 19 made 19 made 20 to 20 to 21 document 21 document 23 ontogeny 22 the 23 ontogeny 23 ontogeny 24 of 24 of 26 sleep 25 zebrafish 26 sleep 27 - 28 wake 28 wake 29 cycles because sleep differs across phylogeny and ontogeny it is important to validate the use of zebrafish in elucidating the neural substrates of sleep . 0 ###LEFT-WALL### 8 it 0 ###LEFT-WALL### 9 is 0 ###LEFT-WALL### 24 . 1 because 2 sleep 1 because 3 differs 1 because 8 it 2 sleep 3 differs 3 differs 4 across 4 across 6 and 5 phylogeny 6 and 6 and 7 ontogeny 8 it 9 is 9 is 10 important 10 important 11 to 10 important 12 validate 11 to 12 validate 12 validate 14 use 12 validate 17 in 13 the 14 use 14 use 15 of 15 of 16 zebrafish 17 in 18 elucidating 18 elucidating 21 substrates 19 the 21 substrates 20 neural 21 substrates 21 substrates 22 of 22 of 23 sleep here we describe the development of sleep and wake across the zebrafish lifespan and how it compares to humans . 0 ###LEFT-WALL### 2 we 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 20 . 1 here 2 we 2 we 8 and 3 describe 5 development 3 describe 8 and 4 the 5 development 5 development 6 of 6 of 7 sleep 8 and 9 wake 8 and 10 across 10 across 14 and 11 the 13 lifespan 12 zebrafish 13 lifespan 13 lifespan 14 and 14 and 15 how 14 and 16 it 14 and 17 compares 16 it 17 compares 17 compares 18 to 18 to 19 humans we find power - law distributions to best fit wake bout data but demonstrate that exponential distributions , previously used to describe sleep bout distributions , fail to adequately account for the data in either species . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 find 0 ###LEFT-WALL### 37 . 1 we 2 find 2 find 3 power 2 find 30 account 3 power 6 distributions 3 power 20 used 4 - 6 distributions 5 law 6 distributions 6 distributions 7 to 6 distributions 14 demonstrate 6 distributions 18 , 7 to 13 but 8 best 12 data 8 best 13 but 9 fit 10 wake 10 wake 11 bout 11 bout 12 data 13 but 14 demonstrate 14 demonstrate 17 distributions 15 that 16 exponential 16 exponential 17 distributions 19 previously 20 used 20 used 21 to 20 used 26 , 21 to 26 , 22 describe 25 distributions 22 describe 26 , 23 sleep 25 distributions 24 bout 25 distributions 26 , 27 fail 27 fail 28 to 28 to 30 account 29 adequately 30 account 30 account 31 for 30 account 34 in 31 for 33 data 32 the 33 data 34 in 36 species 35 either 36 species regardless , the data reveal remarkable similarities in the ontogeny of sleep cycles in zebrafish and humans . 0 ###LEFT-WALL### 4 data 0 ###LEFT-WALL### 5 reveal 0 ###LEFT-WALL### 18 . 1 regardless 2 , 1 regardless 4 data 3 the 4 data 4 data 5 reveal 5 reveal 7 similarities 5 reveal 8 in 5 reveal 14 in 6 remarkable 7 similarities 8 in 10 ontogeny 9 the 10 ontogeny 10 ontogeny 11 of 11 of 13 cycles 12 sleep 13 cycles 14 in 16 and 15 zebrafish 16 and 16 and 17 humans moreover , as [seen] in other organisms , zebrafish sleep levels are [highest] early in ontogeny and sleep and wake bouts gradually consolidate to form the adult sleep pattern . 0 ###LEFT-WALL### 11 levels 0 ###LEFT-WALL### 12 are 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 30 . 1 moreover 2 , 1 moreover 11 levels 2 , 3 as 3 as 5 in 3 as 8 , 3 as 11 levels 5 in 7 organisms 6 other 7 organisms 9 zebrafish 10 sleep 10 sleep 11 levels 11 levels 12 are 12 are 14 early 14 early 15 in 15 in 16 ontogeny 17 and 19 and 17 and 23 consolidate 18 sleep 19 and 19 and 21 bouts 19 and 23 consolidate 20 wake 21 bouts 22 gradually 23 consolidate 23 consolidate 24 to 24 to 25 form 25 form 29 pattern 26 the 29 pattern 27 adult 29 pattern 28 sleep 29 pattern finally , sleep [percentage] , bout duration , bout number , and sleep fragmentation are shown to allow for meaningful comparisons between zebrafish and human sleep . 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 16 shown 0 ###LEFT-WALL### 27 . 1 finally 2 , 1 finally 12 and 3 sleep 5 , 5 , 7 duration 5 , 8 , 6 bout 7 duration 8 , 10 number 8 , 12 and 9 bout 10 number 11 , 12 and 12 and 14 fragmentation 12 and 15 are 13 sleep 14 fragmentation 15 are 16 shown 16 shown 17 to 16 shown 22 between 17 to 19 for 18 allow 19 for 19 for 21 comparisons 20 meaningful 21 comparisons 22 between 24 and 23 zebrafish 24 and 24 and 26 sleep 25 human 26 sleep this research argues that immigrants ' political , social , and economic incorporation experiences , which are embedded in individual life course trajectories and heavily influenced by governmental policies , play an important role in producing diverse health outcomes among older u.s . foreign - born persons . 0 ###LEFT-WALL### 2 research 0 ###LEFT-WALL### 24 and 0 ###LEFT-WALL### 30 , 0 ###LEFT-WALL### 43 . 1 this 2 research 2 research 24 and 3 argues 4 that 3 argues 24 and 4 that 11 and 4 that 22 course 5 immigrants 6 ' 6 ' 9 social 7 political 8 , 7 political 9 social 9 social 11 and 10 , 11 and 11 and 14 experiences 11 and 15 , 11 and 16 which 11 and 17 are 11 and 22 course 12 economic 13 incorporation 13 incorporation 14 experiences 16 which 17 are 17 are 18 embedded 18 embedded 19 in 19 in 21 life 20 individual 21 life 22 course 23 trajectories 24 and 26 influenced 24 and 27 by 25 heavily 26 influenced 27 by 29 policies 28 governmental 29 policies 30 , 31 play 31 play 34 role 31 play 35 in 32 an 33 important 32 an 34 role 33 important 34 role 35 in 36 producing 36 producing 39 outcomes 36 producing 40 among 37 diverse 39 outcomes 38 health 39 outcomes 40 among 42 u.s 41 older 42 u.s 43 . 47 persons 43 . 48 . 44 foreign 45 - 44 foreign 47 persons 46 born 47 persons using data from the 2008 - 2010 american community survey and 1998 - 2010 integrated health interview series , we demonstrate how naturalization , a key indicator of social and political inclusion , is related to functional health in midlife and older age . 0 ###LEFT-WALL### 20 we 0 ###LEFT-WALL### 21 demonstrate 0 ###LEFT-WALL### 44 . 1 using 2 data 1 using 19 , 1 using 20 we 2 data 3 from 3 from 11 and 4 the 6 - 5 2008 6 - 6 - 7 2010 6 - 10 survey 8 american 10 survey 9 community 10 survey 10 survey 11 and 11 and 18 series 12 1998 13 - 13 - 14 2010 13 - 18 series 15 integrated 16 health 16 health 17 interview 17 interview 18 series 20 we 21 demonstrate 21 demonstrate 22 how 22 how 23 naturalization 22 how 35 related 23 naturalization 27 indicator 23 naturalization 34 is 24 , 27 indicator 25 a 27 indicator 26 key 27 indicator 27 indicator 28 of 27 indicator 33 , 28 of 32 inclusion 29 social 30 and 30 and 31 political 30 and 32 inclusion 34 is 35 related 35 related 36 to 35 related 39 in 36 to 38 health 37 functional 38 health 39 in 41 and 40 midlife 41 and 41 and 43 age 42 older 43 age consistent with the theoretical framework , we find that among those foreign - born [who] [immigrated] as children and young adults , naturalized citizens show better health at older ages compared with noncitizens , although this relationship is partly mediated by education . 0 ###LEFT-WALL### 7 we 0 ###LEFT-WALL### 8 find 1 consistent 2 with 1 consistent 6 , 1 consistent 7 we 2 with 5 framework 3 the 5 framework 4 theoretical 5 framework 7 we 8 find 8 find 9 that 8 find 10 among 8 find 12 foreign 10 among 11 those 12 foreign 14 born 12 foreign 17 as 13 - 14 born 17 as 25 show 18 children 19 and 19 and 21 adults 19 and 22 , 19 and 25 show 20 young 21 adults 23 naturalized 25 show 24 citizens 25 show 25 show 27 health 25 show 31 compared 26 better 27 health 27 health 28 at 27 health 31 compared 28 at 30 ages 29 older 30 ages 31 compared 32 with 31 compared 35 although 32 with 33 noncitizens 34 , 35 although 35 although 37 relationship 35 although 40 mediated 35 although 43 . 36 this 37 relationship 37 relationship 38 is 38 is 40 mediated 39 partly 40 mediated 40 mediated 41 by 41 by 42 education but among those older foreign - born who [immigrated] [at] [middle] and older ages , naturalized citizens report worse health compared with noncitizens . 0 ###LEFT-WALL### 18 report 0 ###LEFT-WALL### 24 . 1 but 2 among 1 but 18 report 2 among 17 citizens 3 those 17 citizens 4 older 17 citizens 5 foreign 14 ages 5 foreign 17 citizens 6 - 14 ages 7 born 14 ages 8 who 12 and 12 and 13 older 12 and 14 ages 14 ages 15 , 16 naturalized 17 citizens 18 report 20 health 18 report 21 compared 19 worse 20 health 20 health 21 compared 21 compared 22 with 22 with 23 noncitizens moreover , this negative health selection into naturalization becomes stronger for those naturalizing after the 1996 welfare reform act . 0 ###LEFT-WALL### 6 selection 0 ###LEFT-WALL### 9 becomes 0 ###LEFT-WALL### 20 . 1 moreover 2 , 1 moreover 6 selection 3 this 4 negative 4 negative 5 health 5 health 6 selection 6 selection 7 into 6 selection 9 becomes 7 into 8 naturalization 9 becomes 10 stronger 10 stronger 11 for 11 for 12 those 12 those 13 naturalizing 13 naturalizing 14 after 13 naturalizing 19 act 14 after 16 1996 15 the 16 1996 17 welfare 18 reform 18 reform 19 act adulthood trajectories of outcomes such as depression and the sense of control measure aspects of the human condition that americans may view as objects of change . 0 ###LEFT-WALL### 2 trajectories 0 ###LEFT-WALL### 13 measure 0 ###LEFT-WALL### 27 . 1 adulthood 2 trajectories 2 trajectories 3 of 2 trajectories 13 measure 3 of 4 outcomes 4 outcomes 6 as 4 outcomes 11 of 5 such 6 as 6 as 8 and 7 depression 8 and 8 and 10 sense 9 the 10 sense 11 of 12 control 13 measure 14 aspects 14 aspects 15 of 15 of 18 condition 16 the 18 condition 17 human 18 condition 18 condition 19 that 18 condition 22 view 19 that 20 americans 19 that 22 view 20 americans 21 may 21 may 22 view 22 view 23 as 23 as 24 objects 24 objects 25 of 25 of 26 change social science should provide information on that progress , or its absence . 0 ###LEFT-WALL### 2 science 0 ###LEFT-WALL### 4 provide 0 ###LEFT-WALL### 13 . 1 social 2 science 2 science 3 should 3 should 4 provide 4 provide 5 information 4 provide 6 on 6 on 10 or 7 that 8 progress 8 progress 10 or 9 , 10 or 10 or 12 absence 11 its 12 absence whether these trajectories change their shape , [and] how and why [if] they do , is important theoretically too . 0 ###LEFT-WALL### 1 whether 0 ###LEFT-WALL### 16 is 0 ###LEFT-WALL### 20 . 1 whether 3 trajectories 1 whether 4 change 1 whether 16 is 2 these 3 trajectories 3 trajectories 4 change 4 change 6 shape 5 their 6 shape 6 shape 10 and 7 , 10 and 9 how 10 and 10 and 11 why 10 and 13 they 10 and 14 do 10 and 15 , 13 they 14 do 16 is 17 important 17 important 18 theoretically 17 important 19 too a range of birth cohorts coexist in time , place , and social relationship . 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 15 . 1 a 2 range 2 range 3 of 2 range 12 and 3 of 4 birth 4 birth 5 cohorts 4 birth 9 , 5 cohorts 9 , 6 coexist 7 in 6 coexist 9 , 7 in 8 time 9 , 10 place 11 , 12 and 12 and 14 relationship 13 social 14 relationship each cohort , as it goes through adulthood , follows in aggregate a path left by older ones , reshaping that path as it goes . 0 ###LEFT-WALL### 2 cohort 0 ###LEFT-WALL### 3 , 0 ###LEFT-WALL### 26 . 1 each 2 cohort 3 , 12 aggregate 3 , 19 , 4 as 5 it 4 as 9 , 4 as 12 aggregate 5 it 9 , 6 goes 7 through 6 goes 9 , 7 through 8 adulthood 9 , 10 follows 10 follows 11 in 12 aggregate 14 path 13 a 14 path 14 path 15 left 15 left 16 by 16 by 18 ones 17 older 18 ones 19 , 20 reshaping 19 , 25 goes 20 reshaping 22 path 20 reshaping 23 as 20 reshaping 25 goes 21 that 22 path 23 as 24 it the shapes of the trajectories , and the trends reshaping them , represent two inseparable aspects of the same phenomenon . 0 ###LEFT-WALL### 7 and 0 ###LEFT-WALL### 12 , 0 ###LEFT-WALL### 21 . 1 the 2 shapes 2 shapes 3 of 2 shapes 7 and 3 of 5 trajectories 4 the 5 trajectories 6 , 7 and 7 and 9 trends 7 and 10 reshaping 8 the 9 trends 10 reshaping 11 them 12 , 13 represent 13 represent 14 two 13 represent 16 aspects 15 inseparable 16 aspects 16 aspects 17 of 17 of 20 phenomenon 18 the 19 same 19 same 20 phenomenon this report describes methods for mapping aging trajectories and intercohort trends , using linear latent - growth models of relatively brief [follow] - up data ( six years in the examples ) . 0 ###LEFT-WALL### 2 report 0 ###LEFT-WALL### 3 describes 0 ###LEFT-WALL### 33 . 1 this 2 report 2 report 3 describes 3 describes 4 methods 3 describes 5 for 3 describes 13 using 5 for 6 mapping 6 mapping 9 and 7 aging 8 trajectories 8 trajectories 9 and 9 and 11 trends 9 and 12 , 10 intercohort 11 trends 12 , 13 using 13 using 18 models 13 using 32 ) 14 linear 17 growth 15 latent 16 - 15 latent 17 growth 17 growth 18 models 18 models 19 of 19 of 25 data 20 relatively 21 brief 21 brief 23 - 21 brief 25 data 24 up 25 data 25 data 28 years 26 ( 28 years 27 six 28 years 28 years 29 in 28 years 32 ) 29 in 31 examples 30 the 31 examples the author reviews shared research ideals that led to the model : put theory into modeling , go where the data lead , use what you have , go beyond where you have been , and risk being precisely wrong . 0 ###LEFT-WALL### 3 reviews 0 ###LEFT-WALL### 5 research 0 ###LEFT-WALL### 12 : 0 ###LEFT-WALL### 41 . 1 the 3 reviews 2 author 3 reviews 3 reviews 4 shared 3 reviews 5 research 5 research 6 ideals 5 research 9 to 6 ideals 7 that 6 ideals 8 led 7 that 8 led 9 to 11 model 10 the 11 model 12 : 17 , 13 put 14 theory 13 put 15 into 13 put 17 , 15 into 16 modeling 17 , 36 and 18 go 19 where 18 go 31 where 18 go 36 and 19 where 21 data 19 where 23 , 20 the 21 data 21 data 23 , 22 lead 23 , 23 , 24 use 23 , 25 what 25 what 26 you 25 what 30 beyond 26 you 28 , 27 have 28 , 28 , 29 go 28 , 30 beyond 31 where 32 you 31 where 34 been 32 you 33 have 33 have 34 been 35 , 36 and 36 and 37 risk 37 risk 38 being 38 being 39 precisely 38 being 40 wrong reprogramming of gene expression is fundamental for skeletal muscle adaptations in response to endurance exercise . 0 ###LEFT-WALL### 1 reprogramming 0 ###LEFT-WALL### 5 is 0 ###LEFT-WALL### 16 . 1 reprogramming 2 of 1 reprogramming 5 is 2 of 4 expression 3 gene 4 expression 5 is 6 fundamental 6 fundamental 7 for 6 fundamental 13 to 7 for 10 adaptations 8 skeletal 9 muscle 9 muscle 10 adaptations 11 in 12 response 12 response 13 to 13 to 15 exercise 14 endurance 15 exercise this study investigated the time course - dependent changes in the muscular transcriptome after an endurance exercise trial consisting of 1 h of intense cycling immediately followed by 1 h of intense running . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 investigated 0 ###LEFT-WALL### 7 - 0 ###LEFT-WALL### 34 . 1 this 2 study 2 study 3 investigated 3 investigated 6 course 4 the 6 course 5 time 6 course 7 - 9 changes 8 dependent 9 changes 9 changes 10 in 9 changes 23 of 10 in 13 transcriptome 11 the 13 transcriptome 12 muscular 13 transcriptome 13 transcriptome 14 after 13 transcriptome 19 consisting 14 after 18 trial 15 an 18 trial 16 endurance 18 trial 17 exercise 18 trial 19 consisting 20 of 20 of 22 h 21 1 22 h 23 of 25 cycling 24 intense 25 cycling 25 cycling 27 followed 26 immediately 27 followed 27 followed 28 by 28 by 30 h 29 1 30 h 30 h 31 of 31 of 33 running 32 intense 33 running skeletal muscle samples were taken at baseline , 3 h , 48 h , and 96 h postexercise from eight healthy , endurance - trained men . 0 ###LEFT-WALL### 3 samples 0 ###LEFT-WALL### 5 taken 0 ###LEFT-WALL### 15 and 0 ###LEFT-WALL### 27 . 1 skeletal 2 muscle 2 muscle 3 samples 3 samples 4 were 4 were 5 taken 5 taken 6 at 6 at 7 baseline 7 baseline 10 h 7 baseline 13 h 8 , 10 h 9 3 10 h 10 h 11 , 11 , 13 h 12 48 13 h 13 h 14 , 14 , 15 and 15 and 17 h 15 and 18 postexercise 16 96 17 h 17 h 18 postexercise 18 postexercise 19 from 19 from 26 men 20 eight 26 men 21 healthy 23 endurance 21 healthy 26 men 22 , 23 endurance 23 endurance 24 - 25 trained 26 men rna was extracted from muscle . 0 ###LEFT-WALL### 1 rna 0 ###LEFT-WALL### 3 extracted 0 ###LEFT-WALL### 6 . 1 rna 2 was 2 was 3 extracted 3 extracted 4 from 4 from 5 muscle differential gene expression was evaluated using illumina microarrays and validated with qpcr . 0 ###LEFT-WALL### 3 expression 0 ###LEFT-WALL### 4 was 0 ###LEFT-WALL### 13 . 1 differential 2 gene 2 gene 3 expression 3 expression 4 was 4 was 9 and 5 evaluated 6 using 5 evaluated 8 microarrays 5 evaluated 9 and 6 using 7 illumina 9 and 10 validated 9 and 11 with 11 with 12 qpcr gene set enrichment analysis identified enriched molecular signatures chosen from the molecular signatures database . 0 ###LEFT-WALL### 4 analysis 0 ###LEFT-WALL### 6 enriched 0 ###LEFT-WALL### 15 . 1 gene 3 enrichment 2 set 3 enrichment 3 enrichment 4 analysis 4 analysis 5 identified 4 analysis 6 enriched 6 enriched 8 signatures 7 molecular 8 signatures 8 signatures 9 chosen 9 chosen 10 from 10 from 14 database 11 the 14 database 12 molecular 13 signatures 13 signatures 14 database three hours postexercise , 102 gene sets were upregulated [[] family wise error [rate] ( fwer ) , p < 0.05 ] , including groups of genes related with leukocyte migration , [immune] and chaperone activation , and cyclic amp responsive element binding protein ( creb ) 1 signaling . 0 ###LEFT-WALL### 2 hours 0 ###LEFT-WALL### 34 and 0 ###LEFT-WALL### 50 . 1 three 2 hours 2 hours 7 sets 2 hours 8 were 2 hours 34 and 3 postexercise 4 , 3 postexercise 6 gene 5 102 6 gene 6 gene 7 sets 7 sets 8 were 8 were 11 family 9 upregulated 11 family 12 wise 13 error 12 wise 20 < 12 wise 24 including 12 wise 34 and 13 error 16 fwer 15 ( 16 fwer 16 fwer 17 ) 18 , 20 < 19 p 20 < 20 < 21 0.05 20 < 22 ] 23 , 24 including 24 including 25 groups 24 including 32 , 25 groups 26 of 25 groups 28 related 26 of 27 genes 28 related 29 with 29 with 31 migration 30 leukocyte 31 migration 34 and 35 chaperone 34 and 48 1 35 chaperone 38 and 36 activation 38 and 37 , 38 and 38 and 44 protein 38 and 46 creb 39 cyclic 44 protein 40 amp 43 binding 41 responsive 42 element 42 element 43 binding 43 binding 44 protein 45 ( 46 creb 46 creb 47 ) 48 1 49 signaling forty - eight hours postexercise , among 19 enriched gene sets ( fwer , p < 0.05 ) , two gene sets related to actin cytoskeleton remodeling were upregulated . 0 ###LEFT-WALL### 4 hours 0 ###LEFT-WALL### 5 postexercise 0 ###LEFT-WALL### 19 , 0 ###LEFT-WALL### 30 . 1 forty 2 - 2 - 3 eight 2 - 4 hours 4 hours 5 postexercise 5 postexercise 7 among 6 , 7 among 7 among 11 sets 7 among 19 , 8 19 11 sets 9 enriched 11 sets 10 gene 11 sets 11 sets 13 fwer 12 ( 13 fwer 13 fwer 16 < 13 fwer 19 , 14 , 16 < 15 p 16 < 16 < 17 0.05 16 < 18 ) 19 , 22 sets 19 , 29 upregulated 20 two 21 gene 21 gene 22 sets 22 sets 23 related 22 sets 28 were 23 related 24 to 24 to 27 remodeling 25 actin 26 cytoskeleton 26 cytoskeleton 27 remodeling 28 were 29 upregulated ninety - six hours postexercise , 83 gene sets were enriched ( fwer , p < 0.05 ) , 80 of which were upregulated , including gene groups related to chemokine signaling , cell stress management , and extracellular matrix remodeling . 0 ###LEFT-WALL### 1 ninety 0 ###LEFT-WALL### 2 - 2 - 4 hours 3 six 4 hours 4 hours 9 sets 4 hours 10 were 4 hours 13 fwer 5 postexercise 6 , 5 postexercise 9 sets 7 83 8 gene 8 gene 9 sets 9 sets 10 were 10 were 11 enriched 12 ( 13 fwer 13 fwer 16 < 13 fwer 20 80 13 fwer 42 . 14 , 16 < 15 p 16 < 16 < 17 0.05 16 < 18 ) 19 , 20 80 20 80 21 of 20 80 26 including 20 80 29 related 20 80 30 to 20 80 42 . 21 of 22 which 21 of 24 upregulated 22 which 23 were 23 were 24 upregulated 24 upregulated 25 , 26 including 28 groups 26 including 29 related 27 gene 28 groups 30 to 38 and 31 chemokine 32 signaling 31 chemokine 33 , 33 , 36 management 33 , 38 and 34 cell 35 stress 35 stress 36 management 37 , 38 and 38 and 41 remodeling 39 extracellular 41 remodeling 40 matrix 41 remodeling these data provide comprehensive insights into the molecular pathways involved in acute stress , recovery , and adaptive muscular responses to endurance exercise . 0 ###LEFT-WALL### 2 data 0 ###LEFT-WALL### 3 provide 0 ###LEFT-WALL### 24 . 1 these 2 data 2 data 3 provide 3 provide 5 insights 3 provide 11 in 4 comprehensive 5 insights 5 insights 6 into 5 insights 10 involved 6 into 9 pathways 7 the 9 pathways 8 molecular 9 pathways 11 in 17 and 12 acute 13 stress 13 stress 14 , 14 , 15 recovery 14 , 17 and 16 , 17 and 17 and 20 responses 17 and 21 to 18 adaptive 20 responses 19 muscular 20 responses 21 to 23 exercise 22 endurance 23 exercise the novel 96 h postexercise transcriptome indicates substantial transcriptional activity potentially associated with the prolonged presence of leukocytes in the muscles . 0 ###LEFT-WALL### 6 transcriptome 0 ###LEFT-WALL### 7 indicates 0 ###LEFT-WALL### 22 . 1 the 6 transcriptome 2 novel 6 transcriptome 3 96 4 h 4 h 6 transcriptome 5 postexercise 6 transcriptome 6 transcriptome 7 indicates 7 indicates 10 activity 7 indicates 19 in 8 substantial 10 activity 9 transcriptional 10 activity 10 activity 12 associated 11 potentially 12 associated 12 associated 13 with 13 with 16 presence 14 the 16 presence 15 prolonged 16 presence 16 presence 17 of 17 of 18 leukocytes 19 in 21 muscles 20 the 21 muscles this suggests that muscular recovery , from a transcriptional perspective , is incomplete 96 h after endurance exercise involving muscle damage . 0 ###LEFT-WALL### 1 this 0 ###LEFT-WALL### 2 suggests 0 ###LEFT-WALL### 22 . 1 this 2 suggests 2 suggests 3 that 3 that 5 recovery 3 that 12 is 4 muscular 5 recovery 5 recovery 7 from 5 recovery 12 is 6 , 7 from 7 from 10 perspective 7 from 11 , 8 a 9 transcriptional 8 a 10 perspective 9 transcriptional 10 perspective 12 is 13 incomplete 13 incomplete 16 after 14 96 15 h 15 h 16 after 16 after 18 exercise 17 endurance 18 exercise 18 exercise 19 involving 19 involving 21 damage 20 muscle 21 damage molecular mechanisms underlying neurodegenerative diseases converge at the interface of pathways impacting cellular stress , protein homeostasis and aging . 0 ###LEFT-WALL### 2 mechanisms 0 ###LEFT-WALL### 6 converge 0 ###LEFT-WALL### 20 . 1 molecular 2 mechanisms 2 mechanisms 3 underlying 2 mechanisms 6 converge 3 underlying 5 diseases 4 neurodegenerative 5 diseases 6 converge 7 at 7 at 18 and 8 the 9 interface 9 interface 10 of 9 interface 15 , 10 of 11 pathways 11 pathways 12 impacting 12 impacting 14 stress 13 cellular 14 stress 15 , 17 homeostasis 15 , 18 and 16 protein 17 homeostasis 18 and 19 aging targeting the intrinsic capacities of neuroprotective proteins to restore neuronal function [and/or] [attenuate] degeneration represents a potential means toward therapeutic intervention . 0 ###LEFT-WALL### 1 targeting 0 ###LEFT-WALL### 15 represents 0 ###LEFT-WALL### 22 . 1 targeting 4 capacities 1 targeting 15 represents 2 the 4 capacities 3 intrinsic 4 capacities 4 capacities 5 of 4 capacities 8 to 4 capacities 9 restore 5 of 7 proteins 6 neuroprotective 7 proteins 8 to 9 restore 9 restore 14 degeneration 10 neuronal 11 function 11 function 14 degeneration 15 represents 18 means 15 represents 19 toward 16 a 17 potential 16 a 18 means 17 potential 18 means 19 toward 21 intervention 20 therapeutic 21 intervention the product of the human dyt1 gene , torsina , is a member of the functionally diverse aaa+ family of proteins and exhibits [robust] [molecular] - chaperone - like activity , both in vitro and in vivo . 0 ###LEFT-WALL### 2 product 0 ###LEFT-WALL### 22 and 0 ###LEFT-WALL### 26 - 1 the 2 product 2 product 3 of 2 product 9 torsina 2 product 22 and 3 of 7 gene 4 the 7 gene 5 human 7 gene 6 dyt1 7 gene 8 , 9 torsina 9 torsina 10 , 11 is 13 member 11 is 22 and 12 a 13 member 13 member 14 of 14 of 19 family 15 the 19 family 16 functionally 17 diverse 17 diverse 18 aaa+ 18 aaa+ 19 family 19 family 20 of 20 of 21 proteins 22 and 23 exhibits 26 - 27 chaperone 26 - 38 . 27 chaperone 29 like 27 chaperone 32 both 27 chaperone 35 and 28 - 29 like 29 like 30 activity 29 like 31 , 33 in 34 vitro 34 vitro 35 and 35 and 37 vivo 36 in 37 vivo although mutations in dyt1 are associated with a rare form of heritable generalized dystonia , the native function of torsina seems to be cytoprotective in maintaining the cellular threshold to endoplasmic reticulum ( er ) stress . 0 ###LEFT-WALL### 18 function 0 ###LEFT-WALL### 21 seems 0 ###LEFT-WALL### 37 . 1 although 2 mutations 1 although 6 associated 1 although 15 , 1 although 18 function 2 mutations 3 in 2 mutations 5 are 3 in 4 dyt1 5 are 6 associated 6 associated 7 with 7 with 10 form 8 a 9 rare 8 a 10 form 9 rare 10 form 10 form 11 of 11 of 14 dystonia 12 heritable 14 dystonia 13 generalized 14 dystonia 16 the 18 function 17 native 18 function 18 function 19 of 18 function 21 seems 19 of 20 torsina 21 seems 22 to 21 seems 23 be 22 to 23 be 23 be 24 cytoprotective 24 cytoprotective 25 in 25 in 26 maintaining 26 maintaining 29 threshold 26 maintaining 30 to 27 the 29 threshold 28 cellular 29 threshold 30 to 36 stress 31 endoplasmic 36 stress 32 reticulum 34 er 32 reticulum 36 stress 33 ( 34 er 34 er 35 ) here we explore the potential for torsina to serve as a buffer to attenuate the cellular consequences of misfolded - protein stress as it pertains to the neurodegenerative disease amyotrophic lateral sclerosis ( als ) . 0 ###LEFT-WALL### 2 we 0 ###LEFT-WALL### 3 explore 0 ###LEFT-WALL### 20 - 1 here 2 we 2 we 3 explore 3 explore 5 potential 4 the 5 potential 5 potential 6 for 6 for 7 torsina 7 torsina 8 to 7 torsina 9 serve 7 torsina 19 misfolded 8 to 9 serve 9 serve 10 as 10 as 12 buffer 10 as 19 misfolded 11 a 12 buffer 12 buffer 13 to 12 buffer 18 of 12 buffer 19 misfolded 13 to 14 attenuate 14 attenuate 17 consequences 15 the 17 consequences 16 cellular 17 consequences 17 consequences 18 of 19 misfolded 20 - 20 - 22 stress 20 - 25 pertains 20 - 36 . 21 protein 22 stress 22 stress 23 as 22 stress 25 pertains 23 as 24 it 25 pertains 26 to 26 to 32 sclerosis 27 the 32 sclerosis 28 neurodegenerative 29 disease 29 disease 32 sclerosis 30 amyotrophic 32 sclerosis 31 lateral 32 sclerosis 32 sclerosis 34 als 33 ( 34 als 34 als 35 ) the selective vulnerability of motor neurons to degeneration in als mouse models harboring mutations in superoxide dismutase ( sod1 ) has been found to correlate with regional - specific er stress in brains . 0 ###LEFT-WALL### 3 vulnerability 0 ###LEFT-WALL### 23 found 0 ###LEFT-WALL### 34 . 1 the 3 vulnerability 2 selective 3 vulnerability 3 vulnerability 4 of 3 vulnerability 21 has 4 of 6 neurons 5 motor 6 neurons 6 neurons 7 to 6 neurons 19 sod1 7 to 8 degeneration 8 degeneration 9 in 9 in 12 models 10 als 12 models 11 mouse 12 models 12 models 13 harboring 13 harboring 14 mutations 13 harboring 15 in 15 in 17 dismutase 16 superoxide 17 dismutase 18 ( 19 sod1 19 sod1 20 ) 21 has 22 been 22 been 23 found 23 found 24 to 23 found 26 with 23 found 32 in 24 to 25 correlate 26 with 31 stress 27 regional 28 - 27 regional 31 stress 29 specific 31 stress 30 er 31 stress 32 in 33 brains using caenorhabditis elegans as a system to model er stress , we generated transgenic nematodes overexpressing either wild - type or mutant human sod1 to evaluate their relative impact on er stress induction in vivo . 0 ###LEFT-WALL### 12 we 0 ###LEFT-WALL### 26 evaluate 0 ###LEFT-WALL### 36 . 1 using 3 elegans 1 using 4 as 1 using 7 to 1 using 8 model 1 using 11 , 1 using 12 we 2 caenorhabditis 3 elegans 4 as 6 system 5 a 6 system 7 to 8 model 8 model 10 stress 9 er 10 stress 12 we 13 generated 13 generated 24 sod1 13 generated 25 to 14 transgenic 15 nematodes 15 nematodes 16 overexpressing 15 nematodes 21 or 16 overexpressing 20 type 17 either 20 type 18 wild 19 - 18 wild 20 type 21 or 22 mutant 21 or 24 sod1 23 human 24 sod1 25 to 26 evaluate 26 evaluate 29 impact 26 evaluate 30 on 26 evaluate 35 vivo 27 their 29 impact 28 relative 29 impact 30 on 33 induction 31 er 32 stress 32 stress 33 induction 34 in 35 vivo these studies revealed a mutant - sod1 - specific increase in er stress that was further exacerbated by changes in temperature , all of which was robustly attenuated by co - expression of torsina . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 3 revealed 0 ###LEFT-WALL### 31 - 0 ###LEFT-WALL### 35 . 1 these 2 studies 2 studies 3 revealed 3 revealed 10 increase 3 revealed 20 in 4 a 5 mutant 4 a 10 increase 5 mutant 7 sod1 5 mutant 8 - 5 mutant 10 increase 6 - 7 sod1 7 sod1 8 - 9 specific 10 increase 10 increase 11 in 10 increase 14 that 10 increase 15 was 11 in 13 stress 12 er 13 stress 14 that 15 was 15 was 17 exacerbated 16 further 17 exacerbated 17 exacerbated 18 by 18 by 19 changes 20 in 21 temperature 21 temperature 23 all 22 , 23 all 23 all 24 of 23 all 29 by 23 all 31 - 24 of 25 which 24 of 28 attenuated 25 which 26 was 26 was 27 robustly 26 was 28 attenuated 29 by 30 co 31 - 32 expression 32 expression 33 of 33 of 34 torsina moreover , through complementary behavioral analysis , torsina was able to restore normal neuronal function [in] mutant g85r sod1 animals . 0 ###LEFT-WALL### 8 torsina 0 ###LEFT-WALL### 9 was 0 ###LEFT-WALL### 21 . 1 moreover 2 , 1 moreover 8 torsina 2 , 3 through 3 through 6 analysis 3 through 7 , 3 through 8 torsina 4 complementary 6 analysis 5 behavioral 6 analysis 8 torsina 9 was 9 was 10 able 10 able 11 to 10 able 12 restore 11 to 12 restore 12 restore 20 animals 13 normal 15 function 14 neuronal 15 function 15 function 20 animals 17 mutant 20 animals 18 g85r 19 sod1 19 sod1 20 animals furthermore , torsina targeted mutant sod1 for degradation via the proteasome , representing mechanistic insight on the activity that torsina has [on] aggregate - prone proteins . 0 ###LEFT-WALL### 3 torsina 0 ###LEFT-WALL### 4 targeted 0 ###LEFT-WALL### 24 - 1 furthermore 2 , 1 furthermore 3 torsina 3 torsina 4 targeted 4 targeted 6 sod1 4 targeted 9 via 4 targeted 13 representing 5 mutant 6 sod1 6 sod1 7 for 7 for 8 degradation 9 via 11 proteasome 10 the 11 proteasome 12 , 13 representing 13 representing 15 insight 13 representing 16 on 13 representing 24 - 14 mechanistic 15 insight 16 on 18 activity 17 the 18 activity 18 activity 20 torsina 18 activity 21 has 19 that 20 torsina 20 torsina 21 has 21 has 23 aggregate 24 - 26 proteins 24 - 27 . 25 prone 26 proteins these results expand our understanding of proteostatic mechanisms influencing neuronal dysfunction in als , while simultaneously highlighting the potential for torsina as a novel target for therapeutic development . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 expand 1 these 2 results 2 results 3 expand 3 expand 5 understanding 4 our 5 understanding 5 understanding 6 of 6 of 8 mechanisms 7 proteostatic 8 mechanisms 8 mechanisms 9 influencing 9 influencing 11 dysfunction 9 influencing 12 in 9 influencing 15 while 10 neuronal 11 dysfunction 12 in 13 als 14 , 15 while 15 while 17 highlighting 15 while 29 . 16 simultaneously 17 highlighting 17 highlighting 19 potential 17 highlighting 20 for 17 highlighting 22 as 18 the 19 potential 20 for 21 torsina 22 as 25 target 23 a 24 novel 23 a 25 target 24 novel 25 target 25 target 26 for 26 for 28 development 27 therapeutic 28 development polyphenols are a broad class of compounds . 0 ###LEFT-WALL### 1 polyphenols 0 ###LEFT-WALL### 2 are 0 ###LEFT-WALL### 8 . 1 polyphenols 2 are 2 are 5 class 3 a 4 broad 3 a 5 class 4 broad 5 class 5 class 6 of 6 of 7 compounds some are ingested in substantial quantities from nutritional sources , more are produced by medicinal plants , and some of them are taken as drugs . 0 ###LEFT-WALL### 1 some 0 ###LEFT-WALL### 3 ingested 0 ###LEFT-WALL### 10 , 0 ###LEFT-WALL### 26 . 1 some 2 are 2 are 3 ingested 3 ingested 4 in 4 in 6 quantities 5 substantial 6 quantities 6 quantities 7 from 7 from 9 sources 8 nutritional 9 sources 10 , 11 more 10 , 13 produced 10 , 18 and 11 more 12 are 12 are 13 produced 13 produced 14 by 14 by 16 plants 15 medicinal 16 plants 17 , 18 and 18 and 21 them 18 and 23 taken 19 some 20 of 19 some 21 them 20 of 21 them 21 them 22 are 22 are 23 taken 23 taken 24 as 24 as 25 drugs it is becoming clear , that a single polyphenol is impacting several cellular pathways . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 5 , 0 ###LEFT-WALL### 15 . 1 it 2 is 2 is 3 becoming 3 becoming 4 clear 5 , 6 that 5 , 11 impacting 6 that 9 polyphenol 6 that 11 impacting 7 a 8 single 7 a 9 polyphenol 8 single 9 polyphenol 9 polyphenol 10 is 10 is 11 impacting 11 impacting 14 pathways 12 several 14 pathways 13 cellular 14 pathways thus , a network approach is becoming feasible , describing the interaction of a single polyphenol with cellular networks . 0 ###LEFT-WALL### 5 approach 0 ###LEFT-WALL### 6 is 1 thus 2 , 1 thus 5 approach 3 a 5 approach 4 network 5 approach 5 approach 6 is 6 is 7 becoming 7 becoming 8 feasible 8 feasible 10 describing 9 , 10 describing 10 describing 12 interaction 10 describing 17 with 10 describing 20 . 11 the 12 interaction 12 interaction 13 of 13 of 16 polyphenol 14 a 15 single 14 a 16 polyphenol 15 single 16 polyphenol 17 with 19 networks 18 cellular 19 networks here we have selected icariin to draw a prototypic network of icariin activities . 0 ###LEFT-WALL### 2 we 0 ###LEFT-WALL### 4 selected 0 ###LEFT-WALL### 14 . 1 here 2 we 2 we 3 have 3 have 4 selected 4 selected 5 icariin 4 selected 6 to 6 to 7 draw 7 draw 10 network 7 draw 13 activities 8 a 9 prototypic 8 a 10 network 9 prototypic 10 network 10 network 11 of 11 of 12 icariin icariin appears to be a promising drug to treat major age - related diseases , like neurodegeneration , memory and depressive disorders , chronic inflammation , diabetes , and osteoporosis . 0 ###LEFT-WALL### 1 icariin 0 ###LEFT-WALL### 2 appears 0 ###LEFT-WALL### 31 . 1 icariin 2 appears 2 appears 3 to 2 appears 8 to 2 appears 9 treat 3 to 4 be 4 be 7 drug 5 a 6 promising 5 a 7 drug 6 promising 7 drug 8 to 9 treat 9 treat 11 age 9 treat 16 like 10 major 11 age 11 age 14 diseases 12 - 14 diseases 13 related 14 diseases 14 diseases 15 , 16 like 29 and 17 neurodegeneration 18 , 18 , 19 memory 18 , 20 and 20 and 22 disorders 20 and 25 inflammation 20 and 27 diabetes 20 and 29 and 21 depressive 22 disorders 23 , 25 inflammation 24 chronic 25 inflammation 25 inflammation 26 , 26 , 27 diabetes 27 diabetes 28 , 29 and 30 osteoporosis it interacts with several relevant pathways , like pde , tgf - ß , mapk , ppar , nos , igf , sirtuin , and others . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 2 interacts 0 ###LEFT-WALL### 12 - 1 it 2 interacts 2 interacts 3 with 3 with 6 pathways 4 several 6 pathways 5 relevant 6 pathways 6 pathways 8 like 7 , 8 like 8 like 11 tgf 8 like 12 - 9 pde 11 tgf 10 , 11 tgf 12 - 25 and 12 - 27 . 13 ß 14 , 14 , 21 igf 14 , 22 , 15 mapk 17 ppar 16 , 17 ppar 17 ppar 19 nos 18 , 19 nos 19 nos 20 , 19 nos 21 igf 22 , 23 sirtuin 22 , 25 and 24 , 25 and 25 and 26 others such networks will be useful to future comparative studies of complex effects of polyphenols . 0 ###LEFT-WALL### 2 networks 0 ###LEFT-WALL### 4 be 0 ###LEFT-WALL### 15 . 1 such 2 networks 2 networks 3 will 3 will 4 be 4 be 5 useful 5 useful 6 to 6 to 9 studies 7 future 9 studies 8 comparative 9 studies 9 studies 10 of 10 of 12 effects 11 complex 12 effects 12 effects 13 of 13 of 14 polyphenols unlabelled : the aim of the study was to compare preoperative findings , serum levels of calcium and parathormone ( pth ) and outcome of patients undergoing surgery for primary hyperparathyroidism ( phpt ) aged over 70 years with younger patients . 0 ###LEFT-WALL### 1 unlabelled 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 42 . 2 : 4 aim 2 : 8 was 2 : 13 , 3 the 4 aim 4 aim 5 of 4 aim 8 was 5 of 7 study 6 the 7 study 8 was 9 to 9 to 10 compare 10 compare 12 findings 11 preoperative 12 findings 13 , 23 and 13 , 35 aged 14 serum 15 levels 15 levels 16 of 15 levels 18 and 16 of 17 calcium 18 and 19 parathormone 18 and 21 pth 18 and 23 and 20 ( 21 pth 21 pth 22 ) 23 and 24 outcome 23 and 25 of 23 and 27 undergoing 23 and 35 aged 25 of 26 patients 27 undergoing 28 surgery 28 surgery 29 for 29 for 31 hyperparathyroidism 30 primary 31 hyperparathyroidism 31 hyperparathyroidism 33 phpt 32 ( 33 phpt 33 phpt 34 ) 35 aged 38 years 36 over 37 70 37 70 38 years 38 years 39 with 39 with 41 patients 40 younger 41 patients material and methods : between january 1 , 1996 and september [30] , 2011 186 patients underwent surgery for phpt . 0 ###LEFT-WALL### 3 methods 0 ###LEFT-WALL### 4 : 0 ###LEFT-WALL### 8 , 0 ###LEFT-WALL### 21 . 1 material 2 and 2 and 3 methods 3 methods 4 : 4 : 5 between 5 between 6 january 6 january 7 1 8 , 9 1996 8 , 10 and 10 and 16 patients 10 and 17 underwent 11 september 13 , 11 september 16 patients 14 2011 16 patients 15 186 16 patients 16 patients 17 underwent 17 underwent 18 surgery 18 surgery 19 for 19 for 20 phpt patient data were collected from chart reviews and an electronically stored database . 0 ###LEFT-WALL### 2 data 0 ###LEFT-WALL### 3 were 0 ###LEFT-WALL### 13 . 1 patient 2 data 2 data 3 were 3 were 4 collected 4 collected 5 from 5 from 8 and 6 chart 7 reviews 7 reviews 8 and 8 and 12 database 9 an 12 database 10 electronically 11 stored 11 stored 12 database groups were defined as patients aged 70 years or older and patients younger than 70 years . 0 ###LEFT-WALL### 1 groups 0 ###LEFT-WALL### 3 defined 0 ###LEFT-WALL### 17 . 1 groups 2 were 2 were 3 defined 3 defined 4 as 3 defined 13 younger 4 as 11 and 5 patients 6 aged 5 patients 11 and 6 aged 9 or 7 70 8 years 8 years 9 or 9 or 10 older 11 and 12 patients 13 younger 14 than 14 than 16 years 15 70 16 years outcome comparison included operation time , tumor size , pre - and postoperative serum levels of calcium and pth and length [of] stay in hospital . 0 ###LEFT-WALL### 2 comparison 0 ###LEFT-WALL### 3 included 0 ###LEFT-WALL### 6 , 0 ###LEFT-WALL### 26 . 1 outcome 2 comparison 2 comparison 3 included 3 included 5 time 4 operation 5 time 6 , 25 hospital 7 tumor 8 size 8 size 9 , 9 , 10 pre 9 , 12 and 11 - 12 and 12 and 14 serum 12 and 20 and 12 and 24 in 12 and 25 hospital 13 postoperative 14 serum 15 levels 16 of 15 levels 18 and 16 of 17 calcium 18 and 19 pth 18 and 20 and 20 and 21 length 20 and 23 stay 23 stay 24 in complications were defined as clinical and laboratory signs of hypocalcemia , persistent elevated serum calcium , temporary or persistent recurrent laryngeal nerve paralysis , bleeding with need for reoperation , surgical site infection or need of tracheotomy . 0 ###LEFT-WALL### 1 complications 0 ###LEFT-WALL### 38 . 1 complications 2 were 2 were 3 defined 3 defined 4 as 3 defined 26 with 4 as 6 and 5 clinical 6 and 6 and 8 signs 6 and 9 of 7 laboratory 8 signs 9 of 18 or 10 hypocalcemia 11 , 10 hypocalcemia 14 serum 12 persistent 14 serum 13 elevated 14 serum 14 serum 15 calcium 15 calcium 16 , 16 , 17 temporary 16 , 18 or 18 or 23 paralysis 18 or 24 , 18 or 25 bleeding 19 persistent 22 nerve 20 recurrent 22 nerve 21 laryngeal 22 nerve 22 nerve 23 paralysis 26 with 34 or 27 need 28 for 27 need 30 , 28 for 29 reoperation 30 , 33 infection 30 , 34 or 31 surgical 32 site 32 site 33 infection 34 or 35 need 35 need 36 of 36 of 37 tracheotomy results : parathyroidectomy alone was performed in 39.2 % of patients . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 3 parathyroidectomy 2 : 6 performed 2 : 12 . 3 parathyroidectomy 5 was 4 alone 5 was 5 was 6 performed 6 performed 7 in 7 in 9 % 8 39.2 9 % 9 % 10 of 10 of 11 patients in 60.8 % partial or total thyroidectomy was conducted simultaneously . 0 ###LEFT-WALL### 7 thyroidectomy 0 ###LEFT-WALL### 9 conducted 0 ###LEFT-WALL### 11 . 1 in 3 % 1 in 7 thyroidectomy 2 60.8 3 % 4 partial 5 or 5 or 6 total 5 or 7 thyroidectomy 7 thyroidectomy 8 was 8 was 9 conducted 9 conducted 10 simultaneously more older patients had history of stroke [and/or] suffered [from] diabetes . 0 ###LEFT-WALL### 3 patients 0 ###LEFT-WALL### 4 had 0 ###LEFT-WALL### 12 . 1 more 3 patients 2 older 3 patients 3 patients 4 had 4 had 5 history 5 history 6 of 6 of 11 diabetes 7 stroke 9 suffered 9 suffered 11 diabetes preoperative serum calcium and pth did not differ between groups , but older patients displayed higher postoperative serum calcium ( p=0.01 ) . 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 8 differ 0 ###LEFT-WALL### 12 but 0 ###LEFT-WALL### 23 . 1 preoperative 3 calcium 2 serum 3 calcium 3 calcium 4 and 4 and 5 pth 4 and 6 did 6 did 7 not 6 did 8 differ 8 differ 9 between 9 between 10 groups 11 , 12 but 12 but 14 patients 12 but 15 displayed 13 older 14 patients 14 patients 15 displayed 15 displayed 19 calcium 16 higher 18 serum 17 postoperative 18 serum 18 serum 19 calcium 19 calcium 21 p=0.01 20 ( 21 p=0.01 21 p=0.01 22 ) no significant differences between the two groups were observed regarding duration of surgery , surgical success rates , postoperative complications and hospitalization time . 0 ###LEFT-WALL### 1 no 0 ###LEFT-WALL### 24 . 1 no 21 and 2 significant 3 differences 3 differences 4 between 3 differences 9 observed 3 differences 10 regarding 3 differences 12 of 3 differences 14 , 4 between 6 two 5 the 6 two 6 two 7 groups 6 two 8 were 7 groups 8 were 10 regarding 11 duration 12 of 13 surgery 14 , 17 rates 14 , 18 , 15 surgical 16 success 16 success 17 rates 18 , 20 complications 18 , 21 and 19 postoperative 20 complications 21 and 23 time 22 hospitalization 23 time conclusions : even though older patients had more risk factors , our data suggest that there was no difference in surgical management and outcome . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 17 was 0 ###LEFT-WALL### 25 . 2 : 3 even 2 : 11 , 3 even 4 though 4 though 6 patients 4 though 7 had 5 older 6 patients 6 patients 7 had 7 had 10 factors 8 more 10 factors 9 risk 10 factors 11 , 17 was 12 our 13 data 13 data 14 suggest 14 suggest 15 that 14 suggest 17 was 15 that 16 there 17 was 19 difference 17 was 20 in 18 no 19 difference 20 in 23 and 21 surgical 22 management 22 management 23 and 23 and 24 outcome [decision] for surgical management of phpt should be done regardless of age . 0 ###LEFT-WALL### 2 for 0 ###LEFT-WALL### 8 be 0 ###LEFT-WALL### 13 . 2 for 4 management 3 surgical 4 management 4 management 5 of 4 management 7 should 5 of 6 phpt 7 should 8 be 8 be 9 done 9 done 11 of 10 regardless 11 of 11 of 12 age aims/hypothesis : muscle [mitochondrial] [function] can vary during fasting , but is lower during hyperinsulinaemia in insulin - resistant humans . 0 ###LEFT-WALL### 1 aims/hypothesis 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 21 . 2 : 3 muscle 2 : 11 but 2 : 18 - 3 muscle 11 but 6 can 7 vary 6 can 11 but 7 vary 8 during 8 during 9 fasting 10 , 11 but 11 but 12 is 12 is 13 lower 13 lower 14 during 14 during 15 hyperinsulinaemia 15 hyperinsulinaemia 16 in 16 in 17 insulin 18 - 20 humans 19 resistant 20 humans ageing and hyperlipidaemia may be the culprits , but the mechanisms remain unclear . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 5 be 0 ###LEFT-WALL### 9 but 0 ###LEFT-WALL### 14 . 1 ageing 2 and 2 and 3 hyperlipidaemia 2 and 4 may 4 may 5 be 5 be 7 culprits 6 the 7 culprits 8 , 9 but 9 but 11 mechanisms 9 but 12 remain 10 the 11 mechanisms 11 mechanisms 12 remain 12 remain 13 unclear we hypothesised that [(] 1 [ )(insulin would fail to increase mitochondrial oxidative capacity in [non] [-] diabetic [insulin] - resistant young obese humans and in elderly patients with type 2 diabetes [and] ( 2 ) reducing nefa levels would improve insulin sensitivity by raising oxidative capacity and lowering oxidative stress . 1 we 2 hypothesised 2 hypothesised 3 that 3 that 7 )(insulin 3 that 9 fail 5 1 7 )(insulin 7 )(insulin 8 would 8 would 9 fail 9 fail 10 to 9 fail 11 increase 10 to 11 increase 11 increase 14 capacity 12 mitochondrial 14 capacity 13 oxidative 14 capacity 14 capacity 25 and 15 in 24 humans 15 in 25 and 18 diabetic 20 - 18 diabetic 24 humans 21 resistant 24 humans 22 young 23 obese 23 obese 24 humans 25 and 26 in 26 in 28 patients 27 elderly 28 patients 28 patients 29 with 28 patients 37 reducing 29 with 32 diabetes 30 type 32 diabetes 31 2 32 diabetes 32 diabetes 35 2 34 ( 35 2 35 2 36 ) 37 reducing 38 nefa 38 nefa 39 levels 38 nefa 44 by 38 nefa 45 raising 39 levels 40 would 40 would 41 improve 41 improve 43 sensitivity 41 improve 44 by 42 insulin 43 sensitivity 45 raising 48 and 46 oxidative 47 capacity 47 capacity 48 and 48 and 51 stress 48 and 52 . 49 lowering 51 stress 50 oxidative 51 stress methods : before and after insulin ( 4 , 40 , 100 nmol/l ) [stimulation] , mitochondrial oxidative capacity was measured in permeabilised fibres and isolated mitochondria using high - resolution respirometry , and h2o2 production was assessed fluorimetrically . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 16 , 0 ###LEFT-WALL### 40 . 1 methods 2 : 2 : 4 and 3 before 4 and 4 and 5 after 5 after 6 insulin 6 insulin 8 4 6 insulin 13 nmol/l 7 ( 8 4 8 4 10 40 8 4 11 , 9 , 10 40 10 40 11 , 11 , 13 nmol/l 12 100 13 nmol/l 13 nmol/l 14 ) 16 , 19 capacity 16 , 25 and 16 , 34 and 17 mitochondrial 19 capacity 18 oxidative 19 capacity 19 capacity 25 and 20 was 21 measured 20 was 25 and 21 measured 22 in 22 in 24 fibres 23 permeabilised 24 fibres 25 and 26 isolated 26 isolated 27 mitochondria 26 isolated 28 using 28 using 32 respirometry 29 high 30 - 29 high 31 resolution 31 resolution 32 respirometry 33 , 34 and 34 and 36 production 34 and 38 assessed 35 h2o2 36 production 36 production 37 was 37 was 38 assessed 38 assessed 39 fluorimetrically tissue - specific insulin sensitivity was measured with hyperinsulinaemic - euglycaemic clamps combined with stable isotopes . 0 ###LEFT-WALL### 5 sensitivity 0 ###LEFT-WALL### 6 was 0 ###LEFT-WALL### 17 . 1 tissue 2 - 1 tissue 5 sensitivity 3 specific 4 insulin 4 insulin 5 sensitivity 5 sensitivity 6 was 6 was 7 measured 7 measured 8 with 8 with 12 clamps 9 hyperinsulinaemic 10 - 9 hyperinsulinaemic 12 clamps 11 euglycaemic 12 clamps 12 clamps 13 combined 13 combined 14 with 14 with 16 isotopes 15 stable 16 isotopes to test the second hypothesis , in [a] 1 - day randomised , crossover study , 15 patients with type 2 diabetes recruited via local advertisement were assessed for eligibility . 0 ###LEFT-WALL### 1 to 0 ###LEFT-WALL### 2 test 0 ###LEFT-WALL### 16 , 0 ###LEFT-WALL### 31 . 1 to 2 test 2 test 5 hypothesis 2 test 7 in 3 the 4 second 3 the 5 hypothesis 6 , 7 in 7 in 9 1 7 in 16 , 9 1 11 day 9 1 15 study 10 - 11 day 11 day 12 randomised 11 day 13 , 13 , 15 study 14 crossover 15 study 15 study 16 , 16 , 18 patients 16 , 28 assessed 17 15 18 patients 18 patients 19 with 18 patients 22 diabetes 18 patients 23 recruited 18 patients 27 were 19 with 20 type 20 type 21 2 22 diabetes 23 recruited 23 recruited 24 via 24 via 26 advertisement 25 local 26 advertisement 27 were 28 assessed 28 assessed 29 for 29 for 30 eligibility nine patients fulfilled the inclusion criteria ( bmi < 35 kg / [m] ( 2 ) ; age < 65 years [ )(and were allocated [to] and completed the intervention , including oral administration [of] 750 mg placebo or acipimox . 0 ###LEFT-WALL### 2 patients 0 ###LEFT-WALL### 3 fulfilled 0 ###LEFT-WALL### 17 ; 0 ###LEFT-WALL### 27 and 0 ###LEFT-WALL### 41 . 1 nine 2 patients 2 patients 3 fulfilled 3 fulfilled 6 criteria 4 the 6 criteria 5 inclusion 6 criteria 6 criteria 12 / 7 ( 12 / 8 bmi 12 / 9 < 10 35 10 35 11 kg 11 kg 12 / 12 / 15 2 12 / 17 ; 14 ( 15 2 15 2 16 ) 17 ; 23 )(and 18 age 21 years 18 age 23 )(and 19 < 20 65 20 65 21 years 23 )(and 24 were 24 were 27 and 25 allocated 27 and 27 and 28 completed 28 completed 39 or 29 the 30 intervention 30 intervention 31 , 31 , 38 placebo 31 , 39 or 32 including 38 placebo 33 oral 34 administration 34 administration 38 placebo 36 750 37 mg 37 mg 38 placebo 39 or 40 acipimox blinded randomisation was performed by the pharmacy ; all participants , researchers performing the measurements and those assessing study outcomes were blinded . 0 ###LEFT-WALL### 2 randomisation 0 ###LEFT-WALL### 4 performed 0 ###LEFT-WALL### 8 ; 0 ###LEFT-WALL### 23 . 1 blinded 2 randomisation 2 randomisation 3 was 3 was 4 performed 4 performed 5 by 5 by 7 pharmacy 6 the 7 pharmacy 8 ; 16 and 9 all 10 participants 10 participants 11 , 11 , 12 researchers 11 , 16 and 12 researchers 13 performing 13 performing 15 measurements 14 the 15 measurements 16 and 17 those 16 and 18 assessing 18 assessing 20 outcomes 18 assessing 22 blinded 19 study 20 outcomes 20 outcomes 21 were 21 were 22 blinded the main outcome measures were insulin sensitivity , oxidative capacity and oxidative stress . 0 ###LEFT-WALL### 4 measures 0 ###LEFT-WALL### 5 were 0 ###LEFT-WALL### 14 . 1 the 2 main 1 the 4 measures 3 outcome 4 measures 4 measures 5 were 5 were 11 and 6 insulin 7 sensitivity 7 sensitivity 8 , 8 , 10 capacity 8 , 11 and 9 oxidative 10 capacity 11 and 13 stress 12 oxidative 13 stress results : insulin sensitivity and mitochondrial oxidative capacity were ~31 % and ~21 [%] lower in the obese groups than in the lean group . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 25 . 2 : 11 % 2 : 12 and 3 insulin 4 sensitivity 4 sensitivity 5 and 5 and 6 mitochondrial 5 and 8 capacity 5 and 10 ~31 5 and 11 % 7 oxidative 8 capacity 8 capacity 9 were 9 were 10 ~31 12 and 13 ~21 12 and 19 groups 13 ~21 15 lower 13 ~21 19 groups 15 lower 16 in 16 in 18 obese 17 the 18 obese 19 groups 20 than 19 groups 21 in 21 in 24 group 22 the 24 group 23 lean 24 group the obese participants also exhibited blunted substrate oxidation upon insulin stimulation . 0 ###LEFT-WALL### 3 participants 0 ###LEFT-WALL### 6 blunted 0 ###LEFT-WALL### 12 . 1 the 3 participants 2 obese 3 participants 3 participants 5 exhibited 3 participants 6 blunted 4 also 5 exhibited 6 blunted 8 oxidation 6 blunted 9 upon 7 substrate 8 oxidation 9 upon 11 stimulation 10 insulin 11 stimulation in the patients with type 2 diabetes , acipimox improved insulin sensitivity by ~27 % and reduced h2o2 production by ~45 % , but did not improve basal or insulin - stimulated mitochondrial oxidative capacity . 0 ###LEFT-WALL### 9 acipimox 0 ###LEFT-WALL### 16 and 0 ###LEFT-WALL### 31 - 0 ###LEFT-WALL### 36 . 1 in 3 patients 1 in 8 , 1 in 9 acipimox 2 the 3 patients 3 patients 4 with 4 with 7 diabetes 5 type 7 diabetes 6 2 7 diabetes 9 acipimox 16 and 10 improved 12 sensitivity 10 improved 13 by 10 improved 16 and 11 insulin 12 sensitivity 13 by 15 % 14 ~27 15 % 16 and 24 but 17 reduced 19 production 17 reduced 20 by 17 reduced 24 but 18 h2o2 19 production 20 by 22 % 21 ~45 22 % 23 , 24 but 24 but 25 did 25 did 26 not 25 did 27 improve 27 improve 29 or 28 basal 29 or 29 or 30 insulin 31 - 35 capacity 32 stimulated 35 capacity 33 mitochondrial 35 capacity 34 oxidative 35 capacity no harmful treatment side effects occurred . 0 ###LEFT-WALL### 5 effects 0 ###LEFT-WALL### 6 occurred 0 ###LEFT-WALL### 7 . 1 no 5 effects 2 harmful 3 treatment 3 treatment 5 effects 4 side 5 effects 5 effects 6 occurred conclusions/interpretation : decreased mitochondrial oxidative capacity can also occur independently of age in insulin - resistant young obese humans . 0 ###LEFT-WALL### 1 conclusions/interpretation 0 ###LEFT-WALL### 2 : 2 : 6 capacity 2 : 9 occur 2 : 15 - 3 decreased 6 capacity 4 mitochondrial 6 capacity 5 oxidative 6 capacity 6 capacity 7 can 7 can 9 occur 8 also 9 occur 9 occur 10 independently 9 occur 13 in 10 independently 11 of 11 of 12 age 13 in 14 insulin 15 - 19 humans 15 - 20 . 16 resistant 19 humans 17 young 19 humans 18 obese 19 humans insulin resistance is present at the muscle mitochondrial level , and is not affected by reducing circulating nefas in type 2 diabetes . 0 ###LEFT-WALL### 2 resistance 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 23 . 1 insulin 2 resistance 2 resistance 11 and 3 is 4 present 3 is 11 and 4 present 5 at 4 present 9 level 5 at 7 muscle 6 the 7 muscle 8 mitochondrial 9 level 10 , 11 and 11 and 12 is 11 and 19 in 11 and 22 diabetes 12 is 13 not 12 is 15 by 13 not 14 affected 15 by 16 reducing 16 reducing 18 nefas 17 circulating 18 nefas 19 in 20 type 20 type 21 2 thus , impaired plasticity [of] [mitochondrial] [function] is an intrinsic phenomenon that probably occurs independently of lipotoxicity and reduced glucose uptake . 0 ###LEFT-WALL### 4 plasticity 0 ###LEFT-WALL### 18 and 0 ###LEFT-WALL### 22 . 1 thus 2 , 1 thus 4 plasticity 3 impaired 4 plasticity 4 plasticity 18 and 8 is 11 phenomenon 8 is 18 and 9 an 11 phenomenon 10 intrinsic 11 phenomenon 11 phenomenon 12 that 11 phenomenon 14 occurs 12 that 14 occurs 13 probably 14 occurs 14 occurs 15 independently 15 independently 16 of 16 of 17 lipotoxicity 18 and 19 reduced 18 and 21 uptake 20 glucose 21 uptake trial registration : clinical trials nct00943059 funding : this study was funded in part by a grant from the german federal ministry of education and research to the german center for diabetes research ( dzd [e.v] . ) . 0 ###LEFT-WALL### 2 registration 0 ###LEFT-WALL### 3 : 0 ###LEFT-WALL### 8 : 0 ###LEFT-WALL### 39 . 1 trial 2 registration 2 registration 3 : 3 : 7 funding 4 clinical 7 funding 5 trials 6 nct00943059 6 nct00943059 7 funding 8 : 10 study 8 : 12 funded 9 this 10 study 10 study 11 was 11 was 12 funded 12 funded 13 in 12 funded 31 for 13 in 25 and 14 part 15 by 14 part 25 and 15 by 17 grant 16 a 17 grant 17 grant 18 from 17 grant 23 of 18 from 22 ministry 19 the 22 ministry 20 german 21 federal 21 federal 22 ministry 23 of 24 education 25 and 26 research 25 and 27 to 27 to 30 center 28 the 30 center 29 german 30 center 31 for 35 dzd 32 diabetes 33 research 33 research 35 dzd 34 ( 35 dzd 35 dzd 37 . 35 dzd 38 ) none purpose of review : the purpose of this study is to highlight recent advances in nutrition and protein research that have the potential to improve health outcomes and status in ageing adults . 0 ###LEFT-WALL### 1 none 0 ###LEFT-WALL### 13 highlight 0 ###LEFT-WALL### 34 . 1 none 4 review 1 none 12 to 1 none 13 highlight 2 purpose 3 of 3 of 4 review 4 review 5 : 5 : 7 purpose 6 the 7 purpose 7 purpose 8 of 7 purpose 10 study 7 purpose 11 is 8 of 9 this 10 study 11 is 11 is 12 to 13 highlight 15 advances 13 highlight 16 in 13 highlight 25 to 14 recent 15 advances 16 in 18 and 17 nutrition 18 and 18 and 20 research 18 and 21 that 18 and 22 have 19 protein 20 research 21 that 22 have 22 have 24 potential 23 the 24 potential 25 to 26 improve 26 improve 29 and 26 improve 31 in 27 health 28 outcomes 28 outcomes 29 and 29 and 30 status 31 in 33 adults 32 ageing 33 adults recent findings : the beneficial effects of dietary protein on muscle health in older adults continue to be refined . 0 ###LEFT-WALL### 2 findings 0 ###LEFT-WALL### 3 : 1 recent 2 findings 3 : 6 effects 3 : 16 continue 3 : 20 . 4 the 6 effects 5 beneficial 6 effects 6 effects 7 of 6 effects 16 continue 7 of 9 protein 8 dietary 9 protein 9 protein 10 on 10 on 12 health 11 muscle 12 health 12 health 13 in 13 in 15 adults 14 older 15 adults 16 continue 17 to 16 continue 19 refined 17 to 18 be 18 be 19 refined recent research has bolstered support for moderately increasing protein consumption beyond the current recommended dietary allowance by adopting a meal [-] based approach in lieu of a less specific daily recommendation . 0 ###LEFT-WALL### 2 research 0 ###LEFT-WALL### 4 bolstered 0 ###LEFT-WALL### 32 . 1 recent 2 research 2 research 3 has 3 has 4 bolstered 4 bolstered 5 support 4 bolstered 6 for 4 bolstered 17 by 6 for 10 consumption 7 moderately 8 increasing 8 increasing 9 protein 9 protein 10 consumption 10 consumption 11 beyond 11 beyond 16 allowance 12 the 16 allowance 13 current 16 allowance 14 recommended 15 dietary 15 dietary 16 allowance 17 by 18 adopting 18 adopting 23 approach 18 adopting 24 in 19 a 23 approach 20 meal 22 based 22 based 23 approach 24 in 25 lieu 25 lieu 26 of 26 of 31 recommendation 27 a 31 recommendation 28 less 29 specific 29 specific 31 recommendation 30 daily 31 recommendation results from muscle protein anabolism , appetite regulation and satiety research support the contention that meeting a protein threshold ( approximately 30 g/meal ) represents a promising strategy [for] middle - aged and older adults concerned with maintaining muscle mass while controlling body fat . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 32 aged 0 ###LEFT-WALL### 33 and 0 ###LEFT-WALL### 45 . 1 results 2 from 1 results 32 aged 2 from 5 anabolism 3 muscle 5 anabolism 4 protein 5 anabolism 5 anabolism 7 appetite 6 , 7 appetite 7 appetite 9 and 7 appetite 12 support 7 appetite 31 - 8 regulation 9 and 9 and 11 research 9 and 12 support 10 satiety 11 research 12 support 14 contention 13 the 14 contention 14 contention 15 that 15 that 16 meeting 15 that 25 represents 16 meeting 19 threshold 16 meeting 25 represents 17 a 18 protein 17 a 19 threshold 18 protein 19 threshold 19 threshold 23 g/meal 20 ( 23 g/meal 21 approximately 22 30 22 30 23 g/meal 23 g/meal 24 ) 25 represents 30 middle 26 a 27 promising 26 a 30 middle 27 promising 28 strategy 28 strategy 30 middle 33 and 35 adults 33 and 40 mass 34 older 35 adults 35 adults 36 concerned 35 adults 37 with 35 adults 40 mass 37 with 38 maintaining 38 maintaining 39 muscle 40 mass 41 while 41 while 42 controlling 42 controlling 44 fat 43 body 44 fat summary : optimizing dietary protein intake to improve health requires a detailed consideration of topics including muscle protein anabolism , appetite control and satiety . 0 ###LEFT-WALL### 1 summary 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 25 . 2 : 3 optimizing 2 : 10 requires 3 optimizing 6 intake 3 optimizing 7 to 3 optimizing 10 requires 4 dietary 5 protein 5 protein 6 intake 7 to 8 improve 8 improve 9 health 10 requires 23 and 11 a 13 consideration 12 detailed 13 consideration 13 consideration 14 of 13 consideration 20 , 14 of 15 topics 15 topics 16 including 16 including 19 anabolism 17 muscle 19 anabolism 18 protein 19 anabolism 20 , 22 control 20 , 23 and 21 appetite 22 control 23 and 24 satiety although each area of research continues to advance independently , recent collaborative and translational efforts have highlighted broad , translational consistencies related to the daily distribution and quantity of dietary protein . 0 ###LEFT-WALL### 15 efforts 0 ###LEFT-WALL### 17 highlighted 0 ###LEFT-WALL### 32 . 1 although 3 area 1 although 6 continues 1 although 10 , 1 although 15 efforts 2 each 3 area 3 area 4 of 3 area 6 continues 4 of 5 research 6 continues 7 to 6 continues 8 advance 7 to 8 advance 8 advance 9 independently 11 recent 15 efforts 12 collaborative 13 and 13 and 14 translational 13 and 15 efforts 15 efforts 16 have 16 have 17 highlighted 17 highlighted 27 and 18 broad 19 , 18 broad 21 consistencies 20 translational 21 consistencies 21 consistencies 22 related 21 consistencies 23 to 21 consistencies 27 and 23 to 26 distribution 24 the 26 distribution 25 daily 26 distribution 27 and 28 quantity 27 and 29 of 29 of 31 protein 30 dietary 31 protein purpose of review : aging is associated with a decline in cognition . 0 ###LEFT-WALL### 3 review 0 ###LEFT-WALL### 4 : 1 purpose 2 of 2 of 3 review 4 : 5 aging 4 : 7 associated 4 : 13 . 5 aging 6 is 6 is 7 associated 7 associated 8 with 7 associated 11 in 8 with 10 decline 9 a 10 decline 11 in 12 cognition this review examines the available data on the effects of nutrition on cognitive impairment . 0 ###LEFT-WALL### 2 review 0 ###LEFT-WALL### 3 examines 0 ###LEFT-WALL### 15 . 1 this 2 review 2 review 3 examines 3 examines 6 data 3 examines 7 on 3 examines 12 on 4 the 6 data 5 available 6 data 7 on 9 effects 8 the 9 effects 9 effects 10 of 10 of 11 nutrition 12 on 14 impairment 13 cognitive 14 impairment it also explores the mechanism ( [s] [ )(by which food may enhance memory . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 3 explores 1 it 3 explores 2 also 3 explores 3 explores 5 mechanism 4 the 5 mechanism 5 mechanism 9 )(by 6 ( 9 )(by 9 )(by 10 which 9 )(by 11 food 9 )(by 13 enhance 9 )(by 15 . 11 food 12 may 12 may 13 enhance 13 enhance 14 memory recent findings : an increasing body of evidence has supported the role of the mediterranean diet and extra - virgin olive oil in protecting cognition . 0 ###LEFT-WALL### 2 findings 0 ###LEFT-WALL### 3 : 1 recent 2 findings 3 : 6 body 3 : 10 supported 3 : 19 - 3 : 26 . 4 an 6 body 5 increasing 6 body 6 body 7 of 6 body 9 has 7 of 8 evidence 9 has 10 supported 10 supported 12 role 11 the 12 role 12 role 13 of 13 of 17 and 14 the 16 diet 15 mediterranean 16 diet 16 diet 17 and 17 and 18 extra 19 - 22 oil 20 virgin 22 oil 21 olive 22 oil 22 oil 23 in 23 in 24 protecting 24 protecting 25 cognition a number of nutritional formulations to improve deteriorating memory are being studied . 0 ###LEFT-WALL### 2 number 0 ###LEFT-WALL### 10 are 0 ###LEFT-WALL### 13 . 1 a 2 number 2 number 3 of 2 number 8 deteriorating 2 number 10 are 3 of 5 formulations 4 nutritional 5 formulations 5 formulations 6 to 5 formulations 7 improve 6 to 7 improve 8 deteriorating 9 memory 10 are 11 being 11 being 12 studied undernutrition is associated [with] cognitive [decline] . 0 ###LEFT-WALL### 1 undernutrition 0 ###LEFT-WALL### 3 associated 0 ###LEFT-WALL### 7 . 1 undernutrition 2 is 2 is 3 associated 3 associated 5 cognitive hyperglycemia and hypertriglyceridemia cause cognitive impairment . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 4 cause 0 ###LEFT-WALL### 7 . 1 hyperglycemia 2 and 2 and 3 hypertriglyceridemia 2 and 4 cause 4 cause 6 impairment 5 cognitive 6 impairment summary : there are increasing data to support the role of nutrition in maintaining cognition . 0 ###LEFT-WALL### 1 summary 0 ###LEFT-WALL### 2 : 2 : 3 there 2 : 4 are 2 : 16 . 3 there 4 are 4 are 6 data 5 increasing 6 data 6 data 7 to 6 data 8 support 7 to 8 support 8 support 10 role 8 support 13 in 9 the 10 role 10 role 11 of 11 of 12 nutrition 13 in 14 maintaining 14 maintaining 15 cognition introduction : thrombus ages , defined as four relative age phases , are related to different compositions of the intraluminal thrombus ( ilt ) in the abdominal aortic aneurysm ( aaa ) ( tong et al . , 2011b ) . 0 ###LEFT-WALL### 1 introduction 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 41 . 2 : 4 ages 2 : 14 related 3 thrombus 4 ages 4 ages 6 defined 4 ages 13 are 5 , 6 defined 6 defined 7 as 6 defined 12 , 7 as 11 phases 8 four 11 phases 9 relative 11 phases 10 age 11 phases 13 are 14 related 14 related 15 to 14 related 25 in 15 to 17 compositions 16 different 17 compositions 17 compositions 18 of 18 of 21 thrombus 19 the 21 thrombus 20 intraluminal 21 thrombus 21 thrombus 23 ilt 22 ( 23 ilt 23 ilt 24 ) 25 in 29 aneurysm 26 the 29 aneurysm 27 abdominal 29 aneurysm 28 aortic 29 aneurysm 29 aneurysm 31 aaa 29 aneurysm 36 al 29 aneurysm 39 2011b 30 ( 31 aaa 31 aaa 32 ) 33 ( 36 al 34 tong 36 al 35 et 36 al 36 al 37 . 36 al 38 , 38 , 39 2011b 39 2011b 40 ) experimental studies indicate a correlation between the relative thrombus age and the strength of the thrombus - covered wall . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 3 indicate 0 ###LEFT-WALL### 17 - 1 experimental 2 studies 2 studies 3 indicate 3 indicate 5 correlation 3 indicate 6 between 4 a 5 correlation 6 between 11 and 7 the 10 age 8 relative 10 age 9 thrombus 10 age 10 age 11 and 11 and 13 strength 11 and 14 of 12 the 13 strength 14 of 16 thrombus 15 the 16 thrombus 17 - 19 wall 17 - 20 . 18 covered 19 wall methods : on 32 aaa samples we performed peeling tests with the aim to dissect the material [(] [i] [ )(through the ilt thickness , [(] ii ) within the individual ilt layers and [(] iii ) within the aneurysm wall underneath the thrombus by using two extension rates ( 1mm/min , 1mm/s ) . 1 methods 2 : 2 : 3 on 2 : 9 peeling 3 on 6 samples 4 32 6 samples 5 aaa 6 samples 6 samples 7 we 6 samples 8 performed 7 we 8 performed 9 peeling 10 tests 10 tests 11 with 11 with 13 aim 12 the 13 aim 13 aim 14 to 13 aim 15 dissect 14 to 15 dissect 15 dissect 17 material 16 the 17 material 17 material 21 )(through 17 material 29 within 21 )(through 24 thickness 22 the 24 thickness 23 ilt 24 thickness 24 thickness 27 ii 25 , 27 ii 27 ii 28 ) 29 within 41 wall 30 the 41 wall 31 individual 33 layers 32 ilt 33 layers 33 layers 34 and 34 and 36 iii 34 and 37 ) 34 and 38 within 34 and 41 wall 38 within 40 aneurysm 39 the 40 aneurysm 41 wall 42 underneath 41 wall 45 by 41 wall 51 1mm/min 42 underneath 44 thrombus 43 the 44 thrombus 45 by 46 using 46 using 49 rates 47 two 49 rates 48 extension 49 rates 50 ( 51 1mm/min 51 1mm/min 53 1mm/s 51 1mm/min 55 . 52 , 53 1mm/s 53 1mm/s 54 ) histological investigations and mass fraction analysis were performed to characterize the dissected morphology , to determine the relative thrombus age , and to quantify dry weight percentages of elastin and collagen in the aaa wall . 0 ###LEFT-WALL### 1 histological 0 ###LEFT-WALL### 22 and 0 ###LEFT-WALL### 36 . 1 histological 7 were 1 histological 9 to 2 investigations 3 and 3 and 6 analysis 3 and 7 were 4 mass 6 analysis 5 fraction 6 analysis 7 were 8 performed 9 to 22 and 10 characterize 13 morphology 10 characterize 15 to 10 characterize 22 and 11 the 13 morphology 12 dissected 13 morphology 14 , 15 to 15 to 16 determine 15 to 21 , 16 determine 20 age 17 the 20 age 18 relative 20 age 19 thrombus 20 age 22 and 23 to 22 and 24 quantify 23 to 24 quantify 24 quantify 27 percentages 24 quantify 32 in 25 dry 26 weight 26 weight 27 percentages 27 percentages 28 of 28 of 30 and 29 elastin 30 and 30 and 31 collagen 32 in 35 wall 33 the 35 wall 34 aaa 35 wall results : a remarkably lower dissection energy was needed to dissect within the individual ilt layers and through the thicknesses of old thrombi . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 24 . 2 : 6 dissection 3 a 6 dissection 4 remarkably 5 lower 5 lower 6 dissection 6 dissection 7 energy 6 dissection 11 dissect 6 dissection 21 of 7 energy 8 was 8 was 9 needed 9 needed 10 to 10 to 11 dissect 11 dissect 17 and 12 within 16 layers 12 within 17 and 13 the 16 layers 14 individual 16 layers 15 ilt 16 layers 17 and 18 through 18 through 20 thicknesses 19 the 20 thicknesses 21 of 23 thrombi 22 old 23 thrombi with increasing ilt age the dissection energy of the underlying intima - media composite continuously decreased and the anisotropic dissection properties for that composite vanished . 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 25 vanished 0 ###LEFT-WALL### 26 . 1 with 4 age 1 with 17 and 2 increasing 4 age 3 ilt 4 age 5 the 7 energy 6 dissection 7 energy 7 energy 8 of 7 energy 17 and 8 of 14 composite 9 the 14 composite 10 underlying 14 composite 11 intima 12 - 11 intima 13 media 13 media 14 composite 14 composite 16 decreased 15 continuously 16 decreased 17 and 21 properties 17 and 22 for 17 and 25 vanished 18 the 21 properties 19 anisotropic 20 dissection 20 dissection 21 properties 22 for 24 composite 23 that 24 composite the quantified dissection properties were [rate] dependent for both tissue types ( ilt and wall ) . 0 ###LEFT-WALL### 4 properties 0 ###LEFT-WALL### 5 were 0 ###LEFT-WALL### 17 . 1 the 4 properties 2 quantified 3 dissection 3 dissection 4 properties 4 properties 5 were 5 were 7 dependent 7 dependent 8 for 8 for 11 types 9 both 11 types 10 tissue 11 types 11 types 14 and 12 ( 14 and 13 ilt 14 and 14 and 15 wall 14 and 16 ) histology showed that single fibrin fibers or smaller protein clots within the ilt generate smooth dissected surfaces during the peeling . 0 ###LEFT-WALL### 1 histology 0 ###LEFT-WALL### 2 showed 0 ###LEFT-WALL### 21 . 1 histology 2 showed 2 showed 7 or 2 showed 10 clots 2 showed 14 generate 3 that 4 single 4 single 5 fibrin 5 fibrin 6 fibers 6 fibers 7 or 7 or 8 smaller 9 protein 10 clots 10 clots 11 within 10 clots 14 generate 11 within 13 ilt 12 the 13 ilt 14 generate 17 surfaces 14 generate 18 during 15 smooth 17 surfaces 16 dissected 17 surfaces 18 during 20 peeling 19 the 20 peeling there was a notable decrease [in] mass fraction of elastin within the thrombus - covered intima - media composite with ilt age , whereas no significant change was found for that of collagen . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 was 0 ###LEFT-WALL### 17 - 0 ###LEFT-WALL### 29 found 0 ###LEFT-WALL### 34 . 1 there 2 was 2 was 8 fraction 3 a 4 notable 3 a 8 fraction 4 notable 5 decrease 5 decrease 8 fraction 7 mass 8 fraction 8 fraction 9 of 9 of 10 elastin 10 elastin 11 within 11 within 13 thrombus 12 the 13 thrombus 13 thrombus 16 intima 14 - 16 intima 15 covered 16 intima 16 intima 17 - 17 - 18 media 17 - 22 age 18 media 19 composite 18 media 22 age 19 composite 20 with 20 with 21 ilt 22 age 24 whereas 23 , 24 whereas 24 whereas 27 change 25 no 27 change 26 significant 27 change 27 change 28 was 28 was 29 found 29 found 30 for 30 for 31 that 31 that 32 of 32 of 33 collagen conclusions : these findings suggest that intraluminal thrombus aging leads to a higher propensity of dissection for the ilt and the intima - media composite of the aneurysmal wall . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 4 findings 2 : 10 leads 2 : 30 . 3 these 4 findings 4 findings 5 suggest 5 suggest 8 thrombus 6 that 7 intraluminal 7 intraluminal 8 thrombus 8 thrombus 9 aging 8 thrombus 10 leads 9 aging 10 leads 10 leads 11 to 11 to 25 composite 12 a 25 composite 13 higher 14 propensity 14 propensity 15 of 14 propensity 20 and 15 of 16 dissection 16 dissection 17 for 17 for 19 ilt 18 the 19 ilt 20 and 22 intima 20 and 23 - 20 and 25 composite 21 the 22 intima 24 media 25 composite 25 composite 26 of 26 of 29 wall 27 the 29 wall 28 aneurysmal 29 wall vascular endothelial growth factor a ( vegf ) , a key factor in angiogenesis , plays an essential role in skeletal development and postnatal homeostasis . 0 ###LEFT-WALL### 4 factor 0 ###LEFT-WALL### 16 plays 0 ###LEFT-WALL### 26 . 1 vascular 3 growth 2 endothelial 3 growth 3 growth 4 factor 4 factor 5 a 4 factor 7 vegf 4 factor 12 factor 4 factor 16 plays 6 ( 7 vegf 7 vegf 8 ) 9 , 12 factor 10 a 12 factor 11 key 12 factor 12 factor 13 in 12 factor 15 , 13 in 14 angiogenesis 16 plays 19 role 16 plays 20 in 17 an 18 essential 17 an 19 role 18 essential 19 role 20 in 23 and 21 skeletal 22 development 22 development 23 and 23 and 25 homeostasis 24 postnatal 25 homeostasis vegf serves as a survival factor for chondrocytes and couples the resorption of cartilage with bone formation during endochondral ossification . 0 ###LEFT-WALL### 1 vegf 0 ###LEFT-WALL### 2 serves 0 ###LEFT-WALL### 21 . 1 vegf 2 serves 2 serves 3 as 2 serves 15 with 2 serves 18 during 3 as 6 factor 4 a 5 survival 4 a 6 factor 5 survival 6 factor 6 factor 7 for 7 for 9 and 8 chondrocytes 9 and 9 and 10 couples 9 and 12 resorption 11 the 12 resorption 12 resorption 13 of 13 of 14 cartilage 15 with 17 formation 16 bone 17 formation 18 during 20 ossification 19 endochondral 20 ossification recently , it has also been found to regulate the balance between osteoblast and adipocyte differentiation in bone marrow mesenchymal stem cells . 0 ###LEFT-WALL### 3 it 0 ###LEFT-WALL### 7 found 0 ###LEFT-WALL### 23 . 1 recently 2 , 1 recently 3 it 3 it 4 has 4 has 6 been 5 also 6 been 6 been 7 found 7 found 8 to 8 to 9 regulate 9 regulate 11 balance 9 regulate 12 between 10 the 11 balance 12 between 14 and 13 osteoblast 14 and 14 and 16 differentiation 14 and 17 in 15 adipocyte 16 differentiation 17 in 22 cells 18 bone 19 marrow 19 marrow 22 cells 20 mesenchymal 21 stem 21 stem 22 cells surprisingly , this regulatory function of vegf is not based on paracrine signaling involving cell surface receptor activation . 0 ###LEFT-WALL### 5 function 0 ###LEFT-WALL### 8 is 0 ###LEFT-WALL### 19 . 1 surprisingly 2 , 1 surprisingly 5 function 3 this 5 function 4 regulatory 5 function 5 function 6 of 5 function 8 is 6 of 7 vegf 8 is 9 not 8 is 11 on 9 not 10 based 11 on 13 signaling 12 paracrine 13 signaling 13 signaling 14 involving 14 involving 18 activation 15 cell 18 activation 16 surface 18 activation 17 receptor 18 activation instead , the mechanism appears to utilize intracellular vegf , [which] is functionally linked to the nuclear envelope protein lamin a . lamin a and vegf control osteoblast and adipocyte differentiation by regulating the levels of the osteoblast and adipocyte transcription factors runx2 and pparγ , respectively . 0 ###LEFT-WALL### 4 mechanism 0 ###LEFT-WALL### 10 , 0 ###LEFT-WALL### 22 . 1 instead 2 , 1 instead 4 mechanism 3 the 4 mechanism 4 mechanism 10 , 5 appears 6 to 5 appears 7 utilize 5 appears 10 , 6 to 7 utilize 7 utilize 9 vegf 8 intracellular 9 vegf 10 , 12 is 10 , 20 lamin 12 is 14 linked 13 functionally 14 linked 14 linked 15 to 15 to 19 protein 16 the 19 protein 17 nuclear 18 envelope 18 envelope 19 protein 20 lamin 21 a 22 . 29 and 23 lamin 24 a 23 lamin 25 and 25 and 28 osteoblast 25 and 29 and 26 vegf 28 osteoblast 27 control 28 osteoblast 29 and 30 adipocyte 29 and 31 differentiation 29 and 42 factors 31 differentiation 32 by 31 differentiation 36 of 31 differentiation 42 factors 32 by 33 regulating 33 regulating 35 levels 34 the 35 levels 36 of 41 transcription 37 the 41 transcription 38 osteoblast 39 and 39 and 40 adipocyte 39 and 41 transcription 42 factors 45 pparγ 42 factors 47 respectively 43 runx2 44 and 44 and 45 pparγ 46 , 47 respectively 47 respectively 48 . these data raise the intriguing possibility that loss of bone mass [during] aging may be manipulated by controlling the levels and activity of intracellular vegf in bone marrow mesenchymal stem cells . 0 ###LEFT-WALL### 2 data 0 ###LEFT-WALL### 3 raise 0 ###LEFT-WALL### 32 . 1 these 2 data 2 data 3 raise 3 raise 6 possibility 4 the 6 possibility 5 intriguing 6 possibility 6 possibility 7 that 6 possibility 18 controlling 7 that 8 loss 7 that 16 manipulated 8 loss 9 of 8 loss 14 may 9 of 13 aging 10 bone 11 mass 11 mass 13 aging 14 may 15 be 15 be 16 manipulated 16 manipulated 17 by 17 by 18 controlling 18 controlling 21 and 18 controlling 26 in 19 the 20 levels 20 levels 21 and 21 and 22 activity 21 and 23 of 23 of 25 vegf 24 intracellular 25 vegf 26 in 31 cells 27 bone 31 cells 28 marrow 31 cells 29 mesenchymal 30 stem 30 stem 31 cells objective : serum uric acid ( sua ) levels correlate with many recognized cardiovascular risk factors , including age , male sex , hypertension , diabetes mellitus , hypertriglyceridemia , obesity , and insulin resistance . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 10 correlate 2 : 3 serum 3 serum 9 levels 3 serum 10 correlate 4 uric 9 levels 5 acid 7 sua 5 acid 9 levels 6 ( 7 sua 7 sua 8 ) 9 levels 10 correlate 10 correlate 11 with 10 correlate 18 including 11 with 16 factors 12 many 16 factors 13 recognized 16 factors 14 cardiovascular 16 factors 15 risk 16 factors 17 , 18 including 18 including 33 and 18 including 36 . 19 age 20 , 20 , 22 sex 20 , 23 , 21 male 22 sex 23 , 24 hypertension 23 , 25 , 25 , 27 mellitus 25 , 28 , 26 diabetes 27 mellitus 28 , 31 obesity 28 , 33 and 29 hypertriglyceridemia 30 , 29 hypertriglyceridemia 31 obesity 32 , 33 and 33 and 35 resistance 34 insulin 35 resistance the aim of our study was to verify in a large well characterized population sample the relationship between sua values , hypertension , arterial stiffness and subclinical atherosclerosis . 0 ###LEFT-WALL### 2 aim 0 ###LEFT-WALL### 29 . 1 the 2 aim 2 aim 3 of 2 aim 6 was 3 of 5 study 4 our 5 study 6 was 7 to 6 was 8 verify 7 to 8 verify 8 verify 9 in 8 verify 17 relationship 8 verify 18 between 9 in 15 sample 10 a 11 large 10 a 15 sample 11 large 12 well 12 well 13 characterized 13 characterized 14 population 14 population 15 sample 16 the 17 relationship 18 between 26 and 19 sua 20 values 20 values 21 , 21 , 22 hypertension 21 , 23 , 23 , 25 stiffness 23 , 26 and 24 arterial 25 stiffness 26 and 28 atherosclerosis 27 subclinical 28 atherosclerosis methods : for this study , we selected 248 men and 371 women adult patients enrolled in the last brisighella heart study population survey for which a full set of data were available and not consuming antihypertensive , antidiabetic , lipid - lowering and uric acid - lowering drugs . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 6 , 1 methods 2 : 2 : 3 for 3 for 5 study 4 this 5 study 6 , 7 we 6 , 8 selected 6 , 42 - 7 we 8 selected 8 selected 11 and 9 248 10 men 10 men 11 and 11 and 15 patients 12 371 15 patients 13 women 15 patients 14 adult 15 patients 15 patients 16 enrolled 15 patients 25 for 16 enrolled 17 in 17 in 24 survey 18 the 24 survey 19 last 24 survey 20 brisighella 21 heart 21 heart 24 survey 22 study 23 population 23 population 24 survey 25 for 26 which 25 for 29 set 25 for 32 were 27 a 29 set 28 full 29 set 29 set 30 of 29 set 32 were 30 of 31 data 32 were 34 and 33 available 34 and 34 and 35 not 34 and 41 lipid 36 consuming 41 lipid 37 antihypertensive 38 , 37 antihypertensive 41 lipid 39 antidiabetic 40 , 39 antidiabetic 41 lipid 42 - 49 drugs 42 - 50 . 43 lowering 44 and 44 and 45 uric 44 and 49 drugs 46 acid 47 - 46 acid 49 drugs 48 lowering 49 drugs sua and other available variables were related to blood pressure level , carotid - femoral pulse wave velocity ( cfpwv ) and carotid intima - media thickness ( cimt ) . 0 ###LEFT-WALL### 1 sua 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 9 blood 0 ###LEFT-WALL### 31 . 2 and 5 variables 2 and 7 related 3 other 5 variables 4 available 5 variables 5 variables 6 were 6 were 7 related 7 related 8 to 8 to 9 blood 9 blood 24 intima 10 pressure 24 intima 11 level 14 - 11 level 22 and 12 , 14 - 13 carotid 14 - 14 - 18 velocity 14 - 21 ) 15 femoral 16 pulse 16 pulse 17 wave 17 wave 18 velocity 18 velocity 20 cfpwv 19 ( 20 cfpwv 20 cfpwv 21 ) 22 and 23 carotid 22 and 24 intima 24 intima 27 thickness 25 - 27 thickness 26 media 27 thickness 27 thickness 29 cimt 27 thickness 30 ) 28 ( 29 cimt 29 cimt 30 ) results : hypertension prevalence was strongly related to sua quartiles : we found significant differences between the 2nd ( 23.0 % ) and the 3rd quartiles ( 36.4 % ; p [vs] ..y 2nd < 0.05 [ )(, [and] between the 3rd and the 4th quartile ( 56.3 % ; p [vs] ..y 3rd < 0.05 [ )( 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 55 < 0 ###LEFT-WALL### 58 )( 2 : 3 hypertension 2 : 7 related 2 : 11 : 3 hypertension 4 prevalence 3 hypertension 5 was 3 hypertension 7 related 4 prevalence 5 was 6 strongly 7 related 7 related 8 to 8 to 10 quartiles 9 sua 10 quartiles 11 : 12 we 11 : 13 found 11 : 30 ; 11 : 50 ; 12 we 13 found 13 found 23 and 14 significant 15 differences 15 differences 16 between 15 differences 23 and 16 between 18 2nd 17 the 18 2nd 18 2nd 21 % 19 ( 21 % 20 23.0 21 % 21 % 22 ) 23 and 26 quartiles 23 and 29 % 24 the 26 quartiles 25 3rd 26 quartiles 27 ( 29 % 28 36.4 29 % 29 % 30 ; 30 ; 31 p 30 ; 33 ..y 31 p 33 ..y 33 ..y 34 2nd 34 2nd 35 < 35 < 36 0.05 36 0.05 40 between 38 )(, 40 between 40 between 46 quartile 40 between 50 ; 41 the 46 quartile 42 3rd 43 and 43 and 45 4th 43 and 46 quartile 44 the 45 4th 46 quartile 49 % 47 ( 49 % 48 56.3 49 % 49 % 50 ; 50 ; 51 p 50 ; 53 ..y 51 p 53 ..y 53 ..y 54 3rd 54 3rd 55 < 55 < 56 0.05 similarly , the metabolic syndrome prevalence increased significantly at 39.5 % in the 3rd sua quartile ( p < 0.05 [vs] . 2nd ) [and] at 58.9 % in the 4th quartile ( p < 0.05 [vs] [.] [3rd] ) . 0 ###LEFT-WALL### 6 prevalence 0 ###LEFT-WALL### 7 increased 0 ###LEFT-WALL### 22 . 1 similarly 2 , 1 similarly 6 prevalence 3 the 6 prevalence 4 metabolic 5 syndrome 5 syndrome 6 prevalence 6 prevalence 7 increased 7 increased 8 significantly 7 increased 9 at 7 increased 16 quartile 9 at 12 in 10 39.5 12 in 11 % 12 in 13 the 16 quartile 14 3rd 15 sua 15 sua 16 quartile 16 quartile 19 < 17 ( 19 < 18 p 19 < 19 < 20 0.05 22 . 31 4th 22 . 32 quartile 22 . 41 . 23 2nd 24 ) 23 2nd 31 4th 26 at 29 in 26 at 31 4th 27 58.9 29 in 28 % 29 in 30 the 31 4th 31 4th 32 quartile 32 quartile 35 < 33 ( 35 < 34 p 35 < 35 < 36 0.05 35 < 40 ) intima - media thickness gradually [and] significantly rose along quartiles of sua ( [p] for [trend] < 0.0001 ) , in particular , it was 0.86 mm in the 1st quartile , 0.90 in the 2nd , 0.94 in the 3rd , and 0.97 in the last quartile , with significant differences between each quartiles ( all p < [0.05] ) . 0 ###LEFT-WALL### 4 thickness 0 ###LEFT-WALL### 23 , 0 ###LEFT-WALL### 62 . 1 intima 2 - 1 intima 4 thickness 3 media 4 thickness 4 thickness 8 rose 5 gradually 8 rose 7 significantly 8 rose 8 rose 9 along 8 rose 15 for 8 rose 22 particular 9 along 10 quartiles 10 quartiles 11 of 11 of 12 sua 13 ( 15 for 15 for 18 0.0001 15 for 19 ) 17 < 18 0.0001 20 , 22 particular 21 in 22 particular 22 particular 23 , 23 , 24 it 23 , 25 was 23 , 43 and 24 it 25 was 25 was 27 mm 25 was 28 in 26 0.86 27 mm 28 in 31 quartile 29 the 31 quartile 30 1st 31 quartile 31 quartile 33 0.90 31 quartile 38 0.94 32 , 33 0.90 33 0.90 34 in 33 0.90 37 , 34 in 36 2nd 35 the 36 2nd 37 , 38 0.94 38 0.94 39 in 38 0.94 42 , 39 in 41 3rd 40 the 41 3rd 43 and 44 0.97 43 and 48 quartile 44 0.97 45 in 44 0.97 48 quartile 45 in 47 last 46 the 47 last 48 quartile 50 with 49 , 50 with 50 with 52 differences 50 with 55 quartiles 50 with 61 ) 51 significant 52 differences 52 differences 53 between 53 between 54 each 55 quartiles 57 all 56 ( 57 all 57 all 58 p 57 all 59 < 57 all 61 ) 58 p 59 < in multivariate regression analyses , sua resulted to be significantly associated to hypertension [and] metabolic syndrome prevalence , and imt . 0 ###LEFT-WALL### 6 sua 0 ###LEFT-WALL### 7 resulted 0 ###LEFT-WALL### 21 . 1 in 2 multivariate 1 in 5 , 1 in 6 sua 2 multivariate 3 regression 2 multivariate 4 analyses 3 regression 4 analyses 6 sua 7 resulted 7 resulted 8 to 8 to 9 be 9 be 11 associated 10 significantly 11 associated 11 associated 12 to 12 to 19 and 13 hypertension 17 prevalence 15 metabolic 16 syndrome 16 syndrome 17 prevalence 17 prevalence 19 and 18 , 19 and 19 and 20 imt even if a significant association between sua and cfpwv was found in univariate analysis ( p = 0.002 ) , when adjusting for age , the trend became nonsignificant ( 0.20 ) . 0 ###LEFT-WALL### 27 trend 0 ###LEFT-WALL### 28 became 0 ###LEFT-WALL### 33 . 1 even 2 if 1 even 25 , 1 even 27 trend 2 if 5 association 2 if 11 found 3 a 4 significant 3 a 5 association 4 significant 5 association 5 association 6 between 5 association 10 was 6 between 8 and 7 sua 8 and 8 and 9 cfpwv 10 was 11 found 11 found 12 in 11 found 17 = 11 found 21 when 12 in 14 analysis 13 univariate 14 analysis 15 ( 17 = 16 p 17 = 17 = 18 0.002 17 = 19 ) 20 , 21 when 21 when 22 adjusting 21 when 25 , 22 adjusting 23 for 23 for 24 age 26 the 27 trend 27 trend 28 became 28 became 29 nonsignificant 29 nonsignificant 31 0.20 30 ( 31 0.20 31 0.20 32 ) conclusion : in the studied population sample , after adjustment for a large number of parameters , sua appears to be significantly correlated to hypertension [and] imt , but not to aortic stiffness . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 17 , 0 ###LEFT-WALL### 21 be 0 ###LEFT-WALL### 34 . 1 conclusion 2 : 2 : 3 in 2 : 9 after 3 in 7 sample 4 the 7 sample 5 studied 6 population 6 population 7 sample 8 , 9 after 9 after 10 adjustment 9 after 17 , 10 adjustment 11 for 11 for 14 number 12 a 13 large 12 a 14 number 13 large 14 number 14 number 15 of 15 of 16 parameters 17 , 21 be 18 sua 19 appears 19 appears 20 to 20 to 21 be 21 be 22 significantly 21 be 23 correlated 23 correlated 29 but 24 to 27 imt 24 to 29 but 25 hypertension 27 imt 28 , 29 but 29 but 30 not 29 but 31 to 31 to 33 stiffness 32 aortic 33 stiffness objective : to study the effect of three energy drinks on the color stability of nanofilled composite resins after different periods of aging time . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 25 . 2 : 3 to 2 : 4 study 3 to 4 study 4 study 6 effect 4 study 11 on 4 study 19 after 5 the 6 effect 6 effect 7 of 7 of 10 drinks 8 three 10 drinks 9 energy 10 drinks 11 on 14 stability 12 the 14 stability 13 color 14 stability 14 stability 15 of 15 of 18 resins 16 nanofilled 18 resins 17 composite 18 resins 19 after 21 periods 20 different 21 periods 21 periods 22 of 22 of 23 aging 23 aging 24 time materials and methods : composite resin disks , 6 mm diameter , 3 mm thickness were prepared from filtec z350 xt , tetric evoceram , and filtec z250 xt . 0 ###LEFT-WALL### 3 methods 0 ###LEFT-WALL### 4 : 0 ###LEFT-WALL### 8 , 1 materials 2 and 2 and 3 methods 3 methods 4 : 4 : 7 disks 5 composite 6 resin 6 resin 7 disks 8 , 11 diameter 8 , 12 , 9 6 10 mm 10 mm 11 diameter 12 , 15 thickness 12 , 16 were 13 3 14 mm 14 mm 15 thickness 15 thickness 16 were 16 were 17 prepared 17 prepared 18 from 18 from 26 and 19 filtec 20 z350 20 z350 21 xt 21 xt 22 , 22 , 24 evoceram 22 , 26 and 23 tetric 24 evoceram 25 , 26 and 26 and 29 xt 27 filtec 28 z250 28 z250 29 xt 29 xt 30 . specimens from each material were tested after aging with red bull , bison and power horse energy drinks and distilled water as a control . 0 ###LEFT-WALL### 1 specimens 0 ###LEFT-WALL### 19 and 0 ###LEFT-WALL### 25 . 1 specimens 2 from 1 specimens 5 were 2 from 4 material 3 each 4 material 5 were 19 and 6 tested 7 after 6 tested 9 with 6 tested 17 energy 6 tested 18 drinks 6 tested 19 and 7 after 8 aging 9 with 14 and 10 red 11 bull 11 bull 12 , 12 , 13 bison 12 , 14 and 14 and 16 horse 15 power 16 horse 17 energy 18 drinks 19 and 20 distilled 19 and 22 as 20 distilled 21 water 22 as 24 control 23 a 24 control specimens were stored at 37 °c in dark containers for 1 , 7 , 30 and 60 days . 0 ###LEFT-WALL### 1 specimens 0 ###LEFT-WALL### 3 stored 1 specimens 2 were 2 were 3 stored 3 stored 4 at 3 stored 7 in 4 at 6 °c 5 37 6 °c 7 in 9 containers 8 dark 9 containers 9 containers 10 for 10 for 11 1 11 1 13 7 11 1 18 days 12 , 13 7 13 7 14 , 14 , 18 days 15 30 16 and 16 and 17 60 16 and 18 days 18 days 19 . color was assessed in the cielab using a colorimeter before and after each storage period . 0 ###LEFT-WALL### 1 color 0 ###LEFT-WALL### 3 assessed 0 ###LEFT-WALL### 16 . 1 color 2 was 2 was 3 assessed 3 assessed 4 in 4 in 6 cielab 5 the 6 cielab 6 cielab 7 using 7 using 9 colorimeter 8 a 9 colorimeter 9 colorimeter 11 and 10 before 11 and 11 and 12 after 12 after 15 period 13 each 15 period 14 storage 15 period color differences δe*ab and δb* among specimens were measured . 0 ###LEFT-WALL### 1 color 0 ###LEFT-WALL### 10 . 1 color 2 differences 1 color 9 measured 2 differences 4 and 2 differences 8 were 3 δe*ab 4 and 4 and 5 δb* 4 and 6 among 4 and 8 were 6 among 7 specimens mean values were statistically analyzed using one - way analysis of variance ( anova ) , with [p] < 0.05 as significance level . 0 ###LEFT-WALL### 1 mean 0 ###LEFT-WALL### 24 . 1 mean 2 values 1 mean 5 analyzed 2 values 3 were 3 were 5 analyzed 4 statistically 5 analyzed 5 analyzed 6 using 5 analyzed 17 with 6 using 7 one 7 one 10 analysis 8 - 10 analysis 9 way 10 analysis 10 analysis 11 of 10 analysis 14 anova 10 analysis 16 , 11 of 12 variance 13 ( 14 anova 14 anova 15 ) 17 with 20 0.05 19 < 20 0.05 20 0.05 21 as 21 as 23 level 22 significance 23 level results : the color change δe*ab and δb* occurred by red bull , bison and power horse energy drinks was significantly different for all tested materials at all four times p < 0.05 except in the red bull group . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 25 tested 0 ###LEFT-WALL### 40 . 2 : 6 δe*ab 2 : 7 and 3 the 5 change 4 color 5 change 5 change 6 δe*ab 7 and 8 δb* 7 and 9 occurred 8 δb* 9 occurred 9 occurred 10 by 10 by 11 red 11 red 15 and 11 red 25 tested 12 bull 13 , 13 , 14 bison 13 , 15 and 15 and 16 power 15 and 17 horse 15 and 23 for 15 and 25 tested 17 horse 18 energy 17 horse 19 drinks 17 horse 20 was 18 energy 19 drinks 20 was 21 significantly 20 was 22 different 22 different 23 for 24 all 25 tested 25 tested 26 materials 26 materials 27 at 26 materials 34 except 27 at 30 times 28 all 29 four 29 four 30 times 30 times 32 < 31 p 32 < 32 < 33 0.05 34 except 35 in 35 in 39 group 36 the 39 group 37 red 38 bull 38 bull 39 group all specimens showed increase in color changes toward yellowness δb* after a period of 1 , 7 , 30 and 60 days . 0 ###LEFT-WALL### 1 all 0 ###LEFT-WALL### 7 changes 1 all 2 specimens 1 all 4 increase 1 all 7 changes 2 specimens 3 showed 3 showed 4 increase 4 increase 5 in 5 in 6 color 7 changes 8 toward 8 toward 9 yellowness 9 yellowness 10 δb* 9 yellowness 14 of 9 yellowness 17 7 10 δb* 11 after 11 after 13 period 12 a 13 period 14 of 15 1 16 , 17 7 17 7 22 days 17 7 23 . 18 , 22 days 19 30 20 and 20 and 21 60 20 and 22 days 22 days 23 . the highest total color difference δe*ab was found in the red bull group after 60 days . 0 ###LEFT-WALL### 2 highest 0 ###LEFT-WALL### 13 group 0 ###LEFT-WALL### 17 . 1 the 2 highest 2 highest 6 δe*ab 2 highest 8 found 2 highest 13 group 3 total 4 color 4 color 5 difference 5 difference 6 δe*ab 6 δe*ab 7 was 7 was 8 found 8 found 9 in 9 in 12 bull 10 the 12 bull 11 red 12 bull 13 group 14 after 14 after 16 days 15 60 16 days conclusion : energy drinks used in this study had staining effect on the tested composite resin materials . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 4 drinks 2 : 9 had 2 : 18 . 3 energy 4 drinks 4 drinks 5 used 4 drinks 9 had 5 used 6 in 6 in 8 study 7 this 8 study 9 had 11 effect 9 had 12 on 10 staining 11 effect 12 on 17 materials 13 the 17 materials 14 tested 15 composite 15 composite 17 materials 16 resin 17 materials the discoloration increased with aging time toward yellowness ; however , it was not perceptible in all test groups after 60 days . 0 ###LEFT-WALL### 2 discoloration 0 ###LEFT-WALL### 3 increased 0 ###LEFT-WALL### 9 ; 0 ###LEFT-WALL### 23 . 1 the 2 discoloration 2 discoloration 3 increased 3 increased 4 with 3 increased 6 time 3 increased 7 toward 4 with 5 aging 7 toward 8 yellowness 9 ; 12 it 9 ; 13 was 10 however 11 , 10 however 12 it 12 it 13 was 13 was 14 not 13 was 15 perceptible 15 perceptible 16 in 15 perceptible 20 after 16 in 19 groups 17 all 19 groups 18 test 19 groups 20 after 22 days 21 60 22 days objective : to evaluate the effect of arabic coffee , turkish coffee and nescafe on the color stability of four different composite resins after a period of aging time 1 , 7 and 30 days . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 2 : 13 and 2 : 29 time 3 to 4 evaluate 3 to 10 , 3 to 13 and 4 evaluate 6 effect 5 the 6 effect 6 effect 7 of 7 of 9 coffee 8 arabic 9 coffee 11 turkish 12 coffee 12 coffee 13 and 13 and 14 nescafe 13 and 29 time 14 nescafe 15 on 14 nescafe 27 of 15 on 18 stability 16 the 18 stability 17 color 18 stability 18 stability 19 of 18 stability 24 after 19 of 23 resins 20 four 23 resins 21 different 23 resins 22 composite 23 resins 24 after 26 period 25 a 26 period 27 of 28 aging 29 time 30 1 30 1 35 days 31 , 35 days 32 7 33 and 33 and 34 30 33 and 35 days 35 days 36 . materials and methods : twenty specimens from each type of tested composite resin material were prepared . 0 ###LEFT-WALL### 3 methods 0 ###LEFT-WALL### 4 : 1 materials 2 and 2 and 3 methods 4 : 6 specimens 4 : 15 were 4 : 17 . 5 twenty 6 specimens 6 specimens 7 from 6 specimens 15 were 7 from 14 material 8 each 9 type 9 type 10 of 9 type 14 material 10 of 14 material 11 tested 14 material 12 composite 13 resin 13 resin 14 material 15 were 16 prepared five specimens from each tested material ( z350 xt , artist , gc and z250 ) was evaluated after storage in arabic coffee , turkish coffee , nescafe and distil water ( control ) at 37 °c in a dark container for 1 , 7 and 30 days . 0 ###LEFT-WALL### 2 specimens 0 ###LEFT-WALL### 5 tested 1 five 2 specimens 2 specimens 3 from 2 specimens 5 tested 3 from 4 each 5 tested 6 material 5 tested 29 and 6 material 9 xt 6 material 17 was 7 ( 9 xt 8 z350 9 xt 9 xt 11 artist 9 xt 15 z250 9 xt 16 ) 10 , 11 artist 11 artist 12 , 12 , 15 z250 13 gc 14 and 14 and 15 z250 15 z250 16 ) 17 was 29 and 18 evaluated 19 after 18 evaluated 21 in 18 evaluated 28 nescafe 18 evaluated 29 and 19 after 20 storage 21 in 23 coffee 22 arabic 23 coffee 23 coffee 26 coffee 24 , 26 coffee 25 turkish 26 coffee 26 coffee 27 , 29 and 30 distil 30 distil 31 water 30 distil 35 at 30 distil 38 in 30 distil 42 for 31 water 33 control 32 ( 33 control 33 control 34 ) 35 at 37 °c 36 37 37 °c 38 in 41 container 39 a 41 container 40 dark 41 container 42 for 43 1 43 1 48 days 44 , 48 days 45 7 46 and 46 and 47 30 46 and 48 days 48 days 49 . color measurement was done using colorimeter based on the cie l* a* b* color scale . 0 ###LEFT-WALL### 2 measurement 0 ###LEFT-WALL### 3 was 0 ###LEFT-WALL### 16 . 1 color 2 measurement 2 measurement 3 was 3 was 4 done 4 done 5 using 5 using 6 colorimeter 6 colorimeter 7 based 7 based 8 on 8 on 15 scale 9 the 15 scale 10 cie 14 color 11 l* 13 b* 12 a* 13 b* 13 b* 14 color 14 color 15 scale color differences δe*ab , δb* and δa* among specimens immersed [in] distil water and staining coffee beverages were evaluated overtime . 0 ###LEFT-WALL### 1 color 0 ###LEFT-WALL### 4 , 0 ###LEFT-WALL### 21 . 1 color 2 differences 1 color 3 δe*ab 4 , 6 and 4 , 12 distil 4 , 14 and 5 δb* 6 and 6 and 7 δa* 6 and 8 among 6 and 12 distil 8 among 9 specimens 9 specimens 10 immersed 12 distil 13 water 14 and 17 beverages 14 and 18 were 15 staining 17 beverages 16 coffee 17 beverages 17 beverages 18 were 18 were 20 overtime 19 evaluated 20 overtime mean values were statistically analyzed with one - way analysis of variance ( anova ) , followed by tukey [test] [with] p < 0.05 as significance level . 0 ###LEFT-WALL### 2 values 0 ###LEFT-WALL### 5 analyzed 1 mean 2 values 2 values 3 were 3 were 5 analyzed 4 statistically 5 analyzed 5 analyzed 6 with 6 with 7 one 7 one 10 analysis 8 - 10 analysis 9 way 10 analysis 10 analysis 11 of 10 analysis 17 followed 10 analysis 28 . 11 of 12 variance 12 variance 14 anova 13 ( 14 anova 14 anova 15 ) 16 , 17 followed 17 followed 18 by 17 followed 23 < 17 followed 25 as 17 followed 28 . 18 by 19 tukey 22 p 23 < 23 < 24 0.05 25 as 27 level 26 significance 27 level results : all tested composite resins showed increase color change after a period of 1 , 7 and 30 days . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 3 all 2 : 4 tested 3 all 4 tested 4 tested 6 resins 4 tested 7 showed 5 composite 6 resins 6 resins 7 showed 7 showed 9 color 7 showed 10 change 7 showed 11 after 8 increase 9 color 11 after 13 period 12 a 13 period 13 period 14 of 14 of 15 1 15 1 20 days 16 , 20 days 17 7 18 and 18 and 19 30 18 and 20 days 20 days 21 . the color change δe*ab , δb* and δa* exhibited by arabic coffee , in turkish coffee and nescafe except δa* . 0 ###LEFT-WALL### 7 and 1 the 3 change 2 color 3 change 3 change 4 δe*ab 4 δe*ab 5 , 5 , 6 δb* 5 , 7 and 7 and 8 δa* 7 and 9 exhibited 9 exhibited 10 by 10 by 12 coffee 11 arabic 12 coffee 12 coffee 14 in 13 , 14 in 14 in 17 and 14 in 21 . 15 turkish 16 coffee 16 coffee 17 and 17 and 18 nescafe 17 and 19 except 19 except 20 δa* the highest total color difference δe*ab after 30 days [was] in group a arabic coffee [(] δe > 1.5 perceivable [ )(and not perceivable in group b turkish coffee and group c nescafe . 0 ###LEFT-WALL### 3 total 0 ###LEFT-WALL### 4 color 0 ###LEFT-WALL### 34 . 1 the 2 highest 1 the 3 total 3 total 4 color 4 color 6 δe*ab 4 color 29 coffee 4 color 30 and 5 difference 6 δe*ab 6 δe*ab 7 after 7 after 9 days 8 30 9 days 9 days 17 δe 9 days 18 > 11 in 12 group 11 in 17 δe 12 group 13 a 14 arabic 15 coffee 15 coffee 17 δe 17 δe 18 > 18 > 19 1.5 20 perceivable 22 )(and 22 )(and 23 not 22 )(and 24 perceivable 22 )(and 29 coffee 23 not 24 perceivable 24 perceivable 25 in 25 in 26 group 26 group 27 b 28 turkish 29 coffee 30 and 31 group 30 and 33 nescafe 31 group 32 c for δb* all materials discolored toward yellowness after 30 days except arabic coffee group which shifted from yellowness toward blueness ( δb* [>] 1.5 [perceivable] ) . 0 ###LEFT-WALL### 4 materials 0 ###LEFT-WALL### 5 discolored 0 ###LEFT-WALL### 27 . 1 for 2 δb* 1 for 4 materials 3 all 4 materials 4 materials 5 discolored 5 discolored 6 toward 6 toward 7 yellowness 7 yellowness 8 after 7 yellowness 15 which 7 yellowness 16 shifted 7 yellowness 19 toward 7 yellowness 22 δb* 8 after 9 30 9 30 10 days 9 30 14 group 10 days 11 except 10 days 14 group 11 except 13 coffee 12 arabic 13 coffee 15 which 16 shifted 16 shifted 17 from 17 from 18 yellowness 19 toward 20 blueness 21 ( 22 δb* 22 δb* 24 1.5 22 δb* 26 ) process [-] based cognitive trainings ( pcts ) and novelty interventions are two traditional approaches aiming to prevent cognitive decline [and] dementia . 0 ###LEFT-WALL### 1 process 0 ###LEFT-WALL### 3 based 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 18 prevent 0 ###LEFT-WALL### 23 . 1 process 3 based 3 based 5 trainings 4 cognitive 5 trainings 5 trainings 7 pcts 6 ( 7 pcts 7 pcts 8 ) 9 and 11 interventions 9 and 12 are 10 novelty 11 interventions 11 interventions 12 are 12 are 15 approaches 13 two 15 approaches 14 traditional 15 approaches 15 approaches 16 aiming 16 aiming 17 to 17 to 18 prevent 18 prevent 22 dementia 19 cognitive 20 decline 20 decline 22 dementia however , both have their limitations . 0 ###LEFT-WALL### 3 both 0 ###LEFT-WALL### 4 have 0 ###LEFT-WALL### 7 . 1 however 2 , 1 however 3 both 3 both 4 have 4 have 6 limitations 5 their 6 limitations pcts improve performance only in cognitive tests similar to the training tasks with inconsistent transfer effects on dissimilar tests . 0 ###LEFT-WALL### 1 pcts 0 ###LEFT-WALL### 2 improve 0 ###LEFT-WALL### 20 . 1 pcts 2 improve 2 improve 3 performance 2 improve 4 only 2 improve 13 with 2 improve 17 on 4 only 5 in 5 in 7 tests 6 cognitive 7 tests 7 tests 8 similar 8 similar 9 to 9 to 12 tasks 10 the 12 tasks 11 training 12 tasks 13 with 16 effects 14 inconsistent 15 transfer 15 transfer 16 effects 17 on 19 tests 18 dissimilar 19 tests we argue that this learning specificity is due to a low training task variability . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 argue 0 ###LEFT-WALL### 15 . 1 we 2 argue 2 argue 3 that 3 that 6 specificity 3 that 7 is 4 this 6 specificity 5 learning 6 specificity 6 specificity 7 is 7 is 9 to 8 due 9 to 9 to 14 variability 10 a 11 low 10 a 14 variability 11 low 12 training 12 training 14 variability 13 task 14 variability novelty interventions are characterized by a high task variability but do not target specific processing demands affected in aging and dementia . 0 ###LEFT-WALL### 2 interventions 0 ###LEFT-WALL### 10 but 0 ###LEFT-WALL### 22 . 1 novelty 2 interventions 2 interventions 3 are 3 are 10 but 4 characterized 5 by 4 characterized 9 variability 4 characterized 10 but 5 by 7 high 6 a 7 high 8 task 9 variability 10 but 11 do 11 do 12 not 11 do 13 target 13 target 20 and 14 specific 15 processing 14 specific 18 in 14 specific 20 and 15 processing 16 demands 16 demands 17 affected 18 in 19 aging 20 and 21 dementia to overcome the limitations of both approaches , we developed a process - based novelty intervention using a card and board game - based training approach . 0 ###LEFT-WALL### 9 we 0 ###LEFT-WALL### 10 developed 1 to 2 overcome 1 to 8 , 1 to 9 we 2 overcome 4 limitations 3 the 4 limitations 4 limitations 5 of 5 of 7 approaches 6 both 7 approaches 9 we 10 developed 10 developed 12 process 11 a 12 process 12 process 20 and 13 - 20 and 14 based 15 novelty 15 novelty 16 intervention 16 intervention 17 using 16 intervention 20 and 17 using 19 card 18 a 19 card 20 and 26 approach 20 and 27 . 21 board 26 approach 22 game 23 - 22 game 25 training 24 based 25 training 25 training 26 approach here , we use highly variable tasks , which overlap in targeted processing demands ( " overlapping variability " [framework] ) . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 use 0 ###LEFT-WALL### 8 , 0 ###LEFT-WALL### 22 . 1 here 2 , 1 here 3 we 3 we 4 use 4 use 7 tasks 5 highly 6 variable 6 variable 7 tasks 8 , 9 which 8 , 10 overlap 9 which 10 overlap 10 overlap 11 in 11 in 14 demands 12 targeted 14 demands 13 processing 14 demands 14 demands 17 overlapping 15 ( 16 " 15 ( 17 overlapping 17 overlapping 18 variability 17 overlapping 21 ) 18 variability 19 " another nontraditional training approach combines cognitively with physically challenging tasks to induce multimechanistic effects , which might even interact positively . 0 ###LEFT-WALL### 4 approach 0 ###LEFT-WALL### 5 combines 0 ###LEFT-WALL### 15 , 0 ###LEFT-WALL### 21 . 1 another 4 approach 2 nontraditional 3 training 3 training 4 approach 4 approach 5 combines 5 combines 6 cognitively 5 combines 7 with 7 with 9 challenging 8 physically 9 challenging 9 challenging 10 tasks 9 challenging 11 to 9 challenging 12 induce 11 to 12 induce 12 induce 14 effects 13 multimechanistic 14 effects 15 , 16 which 15 , 19 interact 16 which 17 might 17 might 19 interact 18 even 19 interact 19 interact 20 positively initial results of both synergistic approaches indicate their potential to enhance broad cognitive abilities and prevent dementia . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 15 and 0 ###LEFT-WALL### 18 . 1 initial 2 results 2 results 3 of 2 results 15 and 3 of 6 approaches 4 both 6 approaches 5 synergistic 6 approaches 7 indicate 9 potential 7 indicate 10 to 7 indicate 15 and 8 their 9 potential 10 to 11 enhance 11 enhance 14 abilities 12 broad 14 abilities 13 cognitive 14 abilities 15 and 16 prevent 16 prevent 17 dementia