the data in elderly cohort do [not] [confirm] previously reported role [of] ace dd genotype [to] the development of ht . 0 ###LEFT-WALL### 2 data 0 ###LEFT-WALL### 15 genotype 0 ###LEFT-WALL### 21 . 1 the 2 data 2 data 3 in 2 data 15 genotype 3 in 14 dd 4 elderly 5 cohort 5 cohort 11 role 6 do 11 role 9 previously 10 reported 10 reported 11 role 11 role 14 dd 13 ace 14 dd 15 genotype 18 development 17 the 18 development 18 development 19 of 19 of 20 ht moreover , meta - analysis indicated that ace d allele has some selective advantage that contributes to longevity in majority [of] european populations . 0 ###LEFT-WALL### 5 analysis 0 ###LEFT-WALL### 11 has 0 ###LEFT-WALL### 24 . 1 moreover 2 , 1 moreover 5 analysis 3 meta 4 - 3 meta 5 analysis 5 analysis 6 indicated 5 analysis 7 that 5 analysis 10 allele 5 analysis 11 has 7 that 8 ace 7 that 10 allele 8 ace 9 d 8 ace 10 allele 11 has 14 advantage 11 has 17 to 11 has 19 in 12 some 14 advantage 13 selective 14 advantage 14 advantage 15 that 14 advantage 16 contributes 15 that 16 contributes 17 to 18 longevity 19 in 23 populations 20 majority 23 populations 22 european 23 populations patients with parkinson 's disease ( pd ) are likely to become physically inactive , because of their motor , mental , and emotional symptoms . 0 ###LEFT-WALL### 1 patients 0 ###LEFT-WALL### 12 become 0 ###LEFT-WALL### 20 , 0 ###LEFT-WALL### 26 . 1 patients 2 with 1 patients 9 are 2 with 5 disease 3 parkinson 4 's 4 's 5 disease 5 disease 7 pd 6 ( 7 pd 7 pd 8 ) 9 are 10 likely 10 likely 11 to 11 to 12 become 12 become 13 physically 12 become 14 inactive 14 inactive 17 of 15 , 17 of 16 because 17 of 17 of 19 motor 17 of 20 , 18 their 19 motor 20 , 25 symptoms 21 mental 23 and 22 , 23 and 23 and 24 emotional 23 and 25 symptoms however , specific studies on physical activity in pd are scarce , and results are conflicting . 0 ###LEFT-WALL### 4 studies 0 ###LEFT-WALL### 10 are 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 17 . 1 however 2 , 1 however 4 studies 3 specific 4 studies 4 studies 5 on 4 studies 10 are 5 on 7 activity 6 physical 7 activity 7 activity 8 in 8 in 9 pd 10 are 11 scarce 12 , 13 and 13 and 14 results 13 and 15 are 14 results 15 are 15 are 16 conflicting here , we quantified daily physical activities in a large cohort of pd patients and another large cohort of matched controls . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 quantified 0 ###LEFT-WALL### 22 . 1 here 2 , 1 here 3 we 3 we 4 quantified 4 quantified 7 activities 4 quantified 8 in 5 daily 7 activities 6 physical 7 activities 8 in 11 cohort 9 a 10 large 9 a 11 cohort 10 large 11 cohort 11 cohort 12 of 11 cohort 19 of 12 of 15 and 13 pd 14 patients 14 patients 15 and 15 and 18 cohort 16 another 18 cohort 17 large 18 cohort 19 of 21 controls 20 matched 21 controls moreover , we investigated the influence of disease - related factors on daily physical activities in pd patients . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 investigated 0 ###LEFT-WALL### 10 related 1 moreover 2 , 1 moreover 3 we 3 we 4 investigated 4 investigated 6 influence 5 the 6 influence 6 influence 7 of 7 of 8 disease 9 - 10 related 10 related 11 factors 10 related 12 on 10 related 16 in 10 related 19 . 12 on 15 activities 13 daily 15 activities 14 physical 15 activities 16 in 18 patients 17 pd 18 patients daily physical activity data of pd patients ( n = 699 ) were collected in the parkinsonnet trial [and] of controls ( n = 1,959 ) in the longitudinal aging study amsterdam ( lasa ) ; data were determined using the lapaq , a validated physical activity questionnaire . 0 ###LEFT-WALL### 1 daily 0 ###LEFT-WALL### 13 were 0 ###LEFT-WALL### 36 ; 0 ###LEFT-WALL### 49 . 1 daily 13 were 2 physical 3 activity 3 activity 4 data 4 data 5 of 4 data 10 = 4 data 13 were 5 of 7 patients 6 pd 7 patients 8 ( 10 = 9 n 10 = 10 = 11 699 10 = 12 ) 13 were 14 collected 14 collected 15 in 14 collected 27 in 15 in 18 trial 16 the 18 trial 17 parkinsonnet 18 trial 18 trial 20 of 20 of 21 controls 21 controls 24 = 22 ( 24 = 23 n 24 = 24 = 25 1,959 24 = 26 ) 27 in 34 lasa 28 the 34 lasa 29 longitudinal 30 aging 30 aging 31 study 31 study 32 amsterdam 32 amsterdam 34 lasa 33 ( 34 lasa 34 lasa 35 ) 36 ; 37 data 36 ; 39 determined 36 ; 43 , 37 data 38 were 38 were 39 determined 39 determined 40 using 40 using 42 lapaq 41 the 42 lapaq 43 , 48 questionnaire 44 a 48 questionnaire 45 validated 47 activity 46 physical 47 activity 47 activity 48 questionnaire in addition , variables that may affect daily physical activities in pd were recorded , including motor symptoms , depression , disability in daily life , and comorbidity . 0 ###LEFT-WALL### 4 variables 0 ###LEFT-WALL### 14 recorded 0 ###LEFT-WALL### 21 , 0 ###LEFT-WALL### 29 . 1 in 2 addition 1 in 3 , 1 in 4 variables 4 variables 5 that 4 variables 6 may 4 variables 13 were 5 that 6 may 6 may 7 affect 7 affect 8 daily 7 affect 10 activities 9 physical 10 activities 10 activities 11 in 11 in 12 pd 13 were 14 recorded 14 recorded 16 including 15 , 16 including 16 including 18 symptoms 16 including 21 , 17 motor 18 symptoms 18 symptoms 20 depression 19 , 20 depression 20 depression 21 , 21 , 27 and 22 disability 23 in 22 disability 27 and 23 in 25 life 24 daily 25 life 26 , 27 and 27 and 28 comorbidity patients were physically less active ; a reduction of 29 % compared to controls ( 95 % ci , 10 - 44 % ) . 0 ###LEFT-WALL### 1 patients 0 ###LEFT-WALL### 2 were 0 ###LEFT-WALL### 6 ; 0 ###LEFT-WALL### 25 . 1 patients 2 were 2 were 4 less 2 were 5 active 3 physically 4 less 6 ; 8 reduction 6 ; 12 compared 7 a 8 reduction 8 reduction 9 of 8 reduction 12 compared 9 of 11 % 10 29 11 % 12 compared 13 to 12 compared 21 - 13 to 14 controls 14 controls 18 ci 15 ( 18 ci 16 95 18 ci 17 % 18 ci 18 ci 19 , 19 , 21 - 20 10 21 - 21 - 23 % 21 - 24 ) 22 44 23 % multivariate regression analyses demonstrated that greater disease severity , gait impairment , and greater disability in daily living were associated with less daily physical activity in pd [(] r ( 2 ) = 24 % [ )( 0 ###LEFT-WALL### 1 multivariate 0 ###LEFT-WALL### 4 demonstrated 0 ###LEFT-WALL### 37 )( 1 multivariate 2 regression 1 multivariate 3 analyses 1 multivariate 4 demonstrated 2 regression 3 analyses 4 demonstrated 5 that 5 that 13 and 5 that 20 associated 6 greater 7 disease 7 disease 8 severity 8 severity 9 , 9 , 11 impairment 9 , 13 and 10 gait 11 impairment 12 , 13 and 13 and 15 disability 13 and 16 in 13 and 19 were 14 greater 15 disability 16 in 18 living 17 daily 18 living 19 were 20 associated 20 associated 21 with 21 with 25 activity 21 with 35 % 22 less 25 activity 23 daily 24 physical 24 physical 25 activity 25 activity 26 in 26 in 27 pd 27 pd 29 r 27 pd 31 2 30 ( 31 2 31 2 32 ) 33 = 34 24 34 24 35 % in this large study , we show that pd patients are about one - third less active compared [to] controls . 0 ###LEFT-WALL### 6 we 0 ###LEFT-WALL### 7 show 1 in 4 study 1 in 5 , 1 in 6 we 2 this 3 large 3 large 4 study 6 we 7 show 7 show 8 that 8 that 10 patients 8 that 11 are 9 pd 10 patients 10 patients 11 are 11 are 12 about 12 about 13 one 13 one 20 controls 14 - 20 controls 15 third 20 controls 16 less 17 active 17 active 20 controls 18 compared 20 controls 20 controls 21 . while disease severity , gait , and disability in daily living predicted part of the inactivity , a portion of the variance remained unexplained , suggesting that additional determinants may also affect daily physical activities in pd . 0 ###LEFT-WALL### 7 and 0 ###LEFT-WALL### 12 predicted 0 ###LEFT-WALL### 17 , 1 while 2 disease 1 while 7 and 3 severity 4 , 4 , 5 gait 4 , 7 and 6 , 7 and 7 and 8 disability 7 and 9 in 7 and 12 predicted 9 in 11 living 10 daily 11 living 12 predicted 13 part 13 part 14 of 14 of 16 inactivity 15 the 16 inactivity 17 , 19 portion 17 , 23 remained 18 a 19 portion 19 portion 20 of 19 portion 23 remained 20 of 22 variance 21 the 22 variance 23 remained 24 unexplained 24 unexplained 26 suggesting 25 , 26 suggesting 26 suggesting 29 determinants 26 suggesting 32 affect 26 suggesting 38 . 27 that 28 additional 28 additional 29 determinants 29 determinants 30 may 30 may 32 affect 31 also 32 affect 32 affect 35 activities 33 daily 35 activities 34 physical 35 activities 35 activities 36 in 36 in 37 pd because physical inactivity has many adverse consequences , work is needed to develop safe and enjoyable exercise programs for patients with pd . 0 ###LEFT-WALL### 9 work 0 ###LEFT-WALL### 23 . 1 because 3 inactivity 1 because 4 has 1 because 8 , 1 because 9 work 2 physical 3 inactivity 3 inactivity 4 has 4 has 7 consequences 5 many 7 consequences 6 adverse 7 consequences 9 work 10 is 10 is 11 needed 11 needed 12 to 11 needed 19 for 12 to 13 develop 13 develop 18 programs 14 safe 15 and 15 and 16 enjoyable 15 and 17 exercise 17 exercise 18 programs 19 for 20 patients 20 patients 21 with 21 with 22 pd interleukin - 1β ( il - 1β ) is considered to have a role in age - related cognitive decline . 0 ###LEFT-WALL### 1 interleukin 0 ###LEFT-WALL### 10 considered 0 ###LEFT-WALL### 17 - 1 interleukin 7 1β 1 interleukin 9 is 2 - 7 1β 3 1β 5 il 3 1β 7 1β 4 ( 5 il 5 il 6 - 7 1β 8 ) 9 is 10 considered 10 considered 11 to 10 considered 12 have 11 to 12 have 12 have 14 role 12 have 15 in 13 a 14 role 15 in 16 age 17 - 20 decline 17 - 21 . 18 related 20 decline 19 cognitive 20 decline a recent study has shown that a promoter polymorphism of the il - 1β [gene] ( rs16944 ) is associated with cognitive performance in elderly males without dementia . 0 ###LEFT-WALL### 3 study 0 ###LEFT-WALL### 5 shown 0 ###LEFT-WALL### 29 . 1 a 2 recent 1 a 3 study 2 recent 3 study 3 study 4 has 4 has 5 shown 5 shown 6 that 6 that 9 polymorphism 6 that 20 associated 7 a 9 polymorphism 8 promoter 9 polymorphism 9 polymorphism 10 of 9 polymorphism 19 is 10 of 12 il 11 the 12 il 12 il 14 1β 13 - 14 1β 14 1β 17 rs16944 14 1β 18 ) 16 ( 17 rs16944 17 rs16944 18 ) 19 is 20 associated 20 associated 21 with 21 with 23 performance 22 cognitive 23 performance 23 performance 24 in 23 performance 27 without 24 in 26 males 25 elderly 26 males 27 without 28 dementia in this study , we examined whether polymorphisms of the il [-] 1β gene also influence cognitive functions in elderly females . 0 ###LEFT-WALL### 5 we 0 ###LEFT-WALL### 6 examined 0 ###LEFT-WALL### 22 . 1 in 3 study 1 in 4 , 1 in 5 we 2 this 3 study 5 we 6 examined 6 examined 7 whether 7 whether 8 polymorphisms 7 whether 16 influence 8 polymorphisms 9 of 8 polymorphisms 16 influence 9 of 14 gene 10 the 14 gene 11 il 14 gene 13 1β 14 gene 15 also 16 influence 16 influence 18 functions 16 influence 19 in 17 cognitive 18 functions 19 in 21 females 20 elderly 21 females cognitive functions were assessed by the wechsler adult intelligence scale - revised ( wais - r ) in 99 elderly ( 60 years ) females without dementia . 0 ###LEFT-WALL### 2 functions 0 ###LEFT-WALL### 4 assessed 0 ###LEFT-WALL### 28 . 1 cognitive 2 functions 2 functions 3 were 3 were 4 assessed 4 assessed 5 by 4 assessed 18 in 4 assessed 26 without 5 by 10 scale 6 the 10 scale 7 wechsler 10 scale 8 adult 9 intelligence 9 intelligence 10 scale 10 scale 12 revised 11 - 12 revised 12 revised 15 - 12 revised 17 ) 13 ( 15 - 14 wais 15 - 15 - 16 r 15 - 17 ) 18 in 25 females 19 99 25 females 20 elderly 23 years 20 elderly 24 ) 20 elderly 25 females 21 ( 23 years 22 60 23 years 23 years 24 ) 26 without 27 dementia we selected five tagging polymorphisms from the il [-] 1β gene and examined the associations with the wais - r scores . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 19 - 1 we 12 and 2 selected 5 polymorphisms 2 selected 12 and 3 five 5 polymorphisms 4 tagging 5 polymorphisms 5 polymorphisms 6 from 6 from 11 gene 7 the 11 gene 8 il 11 gene 10 1β 11 gene 12 and 13 examined 13 examined 15 associations 13 examined 16 with 14 the 15 associations 16 with 18 wais 17 the 18 wais 19 - 20 r 19 - 21 scores 19 - 22 . 20 r 21 scores significant associations were found between verbal intelligence [quotient] ( iq ) and [the] genotypes [of] rs1143634 and rs1143633 ( p=0.0037 and p=0.010 , respectively ) . 0 ###LEFT-WALL### 2 associations 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 26 . 1 significant 2 associations 2 associations 12 and 3 were 4 found 3 were 12 and 4 found 5 between 5 between 7 intelligence 6 verbal 7 intelligence 7 intelligence 10 iq 9 ( 10 iq 10 iq 11 ) 12 and 14 genotypes 14 genotypes 17 and 14 genotypes 24 respectively 16 rs1143634 17 and 17 and 18 rs1143633 17 and 21 and 19 ( 21 and 20 p=0.0037 21 and 21 and 22 p=0.010 21 and 23 , 23 , 24 respectively 24 respectively 25 ) no significant associations of rs16944 [genotype] were found with verbal or performance iq . 0 ###LEFT-WALL### 3 associations 0 ###LEFT-WALL### 8 found 0 ###LEFT-WALL### 14 . 1 no 3 associations 2 significant 3 associations 3 associations 4 of 3 associations 7 were 4 of 5 rs16944 7 were 8 found 8 found 9 with 9 with 11 or 10 verbal 11 or 11 or 13 iq 12 performance 13 iq however , individuals homozygous for the [g] allele of rs16944 achieved higher scores [in] [digit] span compared with their counterpart , which is consistent with the previous findings in males . 0 ###LEFT-WALL### 3 individuals 0 ###LEFT-WALL### 17 compared 0 ###LEFT-WALL### 21 , 0 ###LEFT-WALL### 31 . 1 however 2 , 1 however 3 individuals 3 individuals 4 homozygous 3 individuals 9 of 3 individuals 17 compared 4 homozygous 5 for 5 for 8 allele 6 the 8 allele 9 of 10 rs16944 10 rs16944 11 achieved 10 rs16944 13 scores 10 rs16944 16 span 12 higher 13 scores 13 scores 16 span 17 compared 18 with 18 with 20 counterpart 19 their 20 counterpart 21 , 22 which 21 , 23 is 22 which 23 is 23 is 24 consistent 24 consistent 25 with 24 consistent 29 in 25 with 28 findings 26 the 27 previous 26 the 28 findings 29 in 30 males these results suggest that il - 1β gene variation may have a role in cognitive functions in aging females as well as males . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 suggest 0 ###LEFT-WALL### 6 - 0 ###LEFT-WALL### 24 . 1 these 2 results 2 results 3 suggest 3 suggest 5 il 4 that 5 il 6 - 9 variation 6 - 11 have 7 1β 9 variation 8 gene 9 variation 9 variation 10 may 10 may 11 have 11 have 13 role 11 have 14 in 11 have 17 in 11 have 21 well 11 have 22 as 12 a 13 role 14 in 16 functions 15 cognitive 16 functions 17 in 18 aging 18 aging 19 females 20 as 21 well 22 as 23 males the pi3k - akt - foxo signaling pathway plays a central role in diverse physiological processes including cellular energy storage , growth , and survival , among others . 0 ###LEFT-WALL### 8 pathway 0 ###LEFT-WALL### 9 plays 0 ###LEFT-WALL### 29 . 1 the 8 pathway 2 pi3k 4 akt 2 pi3k 8 pathway 3 - 4 akt 4 akt 5 - 6 foxo 8 pathway 7 signaling 8 pathway 8 pathway 9 plays 9 plays 12 role 9 plays 13 in 9 plays 27 among 10 a 12 role 11 central 12 role 13 in 16 processes 14 diverse 16 processes 15 physiological 16 processes 16 processes 17 including 16 processes 24 and 17 including 20 storage 18 cellular 19 energy 19 energy 20 storage 21 , 24 and 22 growth 24 and 23 , 24 and 24 and 25 survival 24 and 26 , 27 among 28 others as an important effector of this pathway , foxo is involved in versatile activities that protect organisms from stress and aging . 0 ###LEFT-WALL### 9 foxo 0 ###LEFT-WALL### 11 involved 0 ###LEFT-WALL### 22 . 1 as 4 effector 1 as 8 , 1 as 9 foxo 2 an 3 important 2 an 4 effector 3 important 4 effector 4 effector 5 of 5 of 7 pathway 6 this 7 pathway 9 foxo 10 is 10 is 11 involved 11 involved 12 in 12 in 14 activities 13 versatile 14 activities 14 activities 15 that 14 activities 16 protect 15 that 16 protect 16 protect 17 organisms 17 organisms 18 from 18 from 20 and 19 stress 20 and 20 and 21 aging recent studies on mammalian foxo have established a direct role for this transcription factor family in cellular [proliferation] , oxidative stress response , and tumorigenesis . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 7 established 0 ###LEFT-WALL### 26 . 1 recent 2 studies 2 studies 3 on 2 studies 6 have 3 on 5 foxo 4 mammalian 5 foxo 6 have 7 established 7 established 10 role 7 established 11 for 7 established 16 in 8 a 9 direct 8 a 10 role 9 direct 10 role 11 for 15 family 12 this 15 family 13 transcription 15 family 14 factor 15 family 16 in 24 and 17 cellular 19 , 19 , 22 response 19 , 24 and 20 oxidative 21 stress 21 stress 22 response 23 , 24 and 24 and 25 tumorigenesis the review will focus on the recent developments pertaining to the function of foxo as well as [discuss] the various contexts in which foxo exerts distinct biological activity such as drug resistance and autophagy in cancer pathogenesis and therapy . 0 ###LEFT-WALL### 33 and 0 ###LEFT-WALL### 40 . 1 the 4 focus 2 review 4 focus 3 will 4 focus 4 focus 5 on 4 focus 10 to 4 focus 33 and 5 on 8 developments 6 the 8 developments 7 recent 8 developments 8 developments 9 pertaining 10 to 12 function 10 to 24 foxo 10 to 25 exerts 11 the 12 function 12 function 13 of 13 of 14 foxo 14 foxo 17 as 15 as 16 well 16 well 17 as 17 as 21 contexts 19 the 21 contexts 20 various 21 contexts 21 contexts 22 in 22 in 23 which 24 foxo 25 exerts 25 exerts 28 activity 26 distinct 28 activity 27 biological 28 activity 28 activity 30 as 29 such 30 as 30 as 32 resistance 31 drug 32 resistance 33 and 34 autophagy 33 and 35 in 35 in 38 and 36 cancer 37 pathogenesis 37 pathogenesis 38 and 38 and 39 therapy the physiological effects of the dietary polyphenol resveratrol are being extensively studied . 0 ###LEFT-WALL### 3 effects 0 ###LEFT-WALL### 9 are 0 ###LEFT-WALL### 13 . 1 the 3 effects 2 physiological 3 effects 3 effects 4 of 3 effects 9 are 4 of 8 resveratrol 5 the 8 resveratrol 6 dietary 7 polyphenol 7 polyphenol 8 resveratrol 9 are 10 being 10 being 12 studied 11 extensively 12 studied resveratrol has been proposed to promote healthy aging and to increase lifespan primarily through the activation of the class iii histone deacetylases ( sirtuins ) . 0 ###LEFT-WALL### 1 resveratrol 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 26 . 1 resveratrol 2 has 2 has 3 been 3 been 9 and 4 proposed 5 to 4 proposed 6 promote 4 proposed 9 and 5 to 6 promote 6 promote 8 aging 7 healthy 8 aging 9 and 10 to 9 and 11 increase 10 to 11 increase 11 increase 12 lifespan 11 increase 13 primarily 13 primarily 14 through 14 through 16 activation 15 the 16 activation 16 activation 17 of 17 of 19 class 18 the 19 class 19 class 20 iii 19 class 21 histone 19 class 22 deacetylases 19 class 24 sirtuins 21 histone 22 deacetylases 23 ( 24 sirtuins 24 sirtuins 25 ) although its positive effects are evident in yeast and mice they still have to be confirmed in humans . 0 ###LEFT-WALL### 11 they 0 ###LEFT-WALL### 13 have 0 ###LEFT-WALL### 19 . 1 although 4 effects 1 although 5 are 1 although 11 they 2 its 4 effects 3 positive 4 effects 4 effects 5 are 5 are 6 evident 6 evident 7 in 7 in 9 and 8 yeast 9 and 9 and 10 mice 11 they 13 have 12 still 13 have 13 have 14 to 13 have 16 confirmed 14 to 15 be 15 be 16 confirmed 16 confirmed 17 in 17 in 18 humans the molecular mechanisms involved in the processes are not fully understood because resveratrol may have other targets than sirtuins and the direct activation of sirtuins by resveratrol is under debate . 0 ###LEFT-WALL### 3 mechanisms 0 ###LEFT-WALL### 11 understood 0 ###LEFT-WALL### 18 than 0 ###LEFT-WALL### 31 . 1 the 3 mechanisms 2 molecular 3 mechanisms 3 mechanisms 4 involved 3 mechanisms 8 are 4 involved 5 in 5 in 7 processes 6 the 7 processes 8 are 9 not 8 are 11 understood 10 fully 11 understood 11 understood 12 because 12 because 13 resveratrol 12 because 15 have 13 resveratrol 14 may 14 may 15 have 15 have 17 targets 16 other 17 targets 18 than 23 activation 18 than 28 is 19 sirtuins 20 and 20 and 22 direct 20 and 23 activation 21 the 22 direct 23 activation 24 of 23 activation 28 is 24 of 25 sirtuins 25 sirtuins 26 by 26 by 27 resveratrol 28 is 29 under 29 under 30 debate consuming protein following exercise has been shown to stimulate protein synthesis acutely in skeletal muscle and has been recommended to prevent sarcopenia . 0 ###LEFT-WALL### 1 consuming 0 ###LEFT-WALL### 16 and 0 ###LEFT-WALL### 23 . 1 consuming 4 exercise 1 consuming 16 and 2 protein 4 exercise 3 following 4 exercise 5 has 6 been 5 has 16 and 6 been 7 shown 7 shown 8 to 8 to 9 stimulate 9 stimulate 11 synthesis 9 stimulate 12 acutely 9 stimulate 13 in 10 protein 11 synthesis 13 in 15 muscle 14 skeletal 15 muscle 16 and 17 has 16 and 20 to 17 has 18 been 18 been 19 recommended 20 to 21 prevent 21 prevent 22 sarcopenia it is not known , however , whether acute stimulation persists long [term] or includes muscle cell division . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 4 known 0 ###LEFT-WALL### 19 . 1 it 2 is 2 is 3 not 2 is 4 known 4 known 6 however 4 known 8 whether 5 , 6 however 6 however 7 , 8 whether 10 stimulation 8 whether 14 or 9 acute 10 stimulation 10 stimulation 14 or 11 persists 12 long 11 persists 14 or 14 or 15 includes 14 or 18 division 16 muscle 18 division 17 cell 18 division we asked here whether consuming protein following exercise during aerobic training increases long - term protein and dna synthesis rates in skeletal muscle of adult humans . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 asked 0 ###LEFT-WALL### 14 - 0 ###LEFT-WALL### 27 . 1 we 2 asked 2 asked 3 here 2 asked 4 whether 4 whether 5 consuming 4 whether 12 increases 5 consuming 6 protein 5 consuming 9 during 5 consuming 12 increases 6 protein 7 following 7 following 8 exercise 9 during 11 training 10 aerobic 11 training 12 increases 13 long 14 - 15 term 15 term 17 and 15 term 20 rates 15 term 21 in 16 protein 17 and 17 and 19 synthesis 18 dna 19 synthesis 21 in 23 muscle 22 skeletal 23 muscle 23 muscle 24 of 24 of 26 humans 25 adult 26 humans sixteen previously untrained participants ( 50 ± [8] yr ) consumed either a carbohydrate or carbohydrate and protein drink following each session during 6 wk of treadmill training . 0 ###LEFT-WALL### 4 participants 0 ###LEFT-WALL### 11 consumed 0 ###LEFT-WALL### 29 . 1 sixteen 4 participants 2 previously 3 untrained 3 untrained 4 participants 4 participants 9 yr 4 participants 11 consumed 5 ( 9 yr 6 50 9 yr 7 ± 9 yr 9 yr 10 ) 11 consumed 17 and 11 consumed 22 session 11 consumed 23 during 12 either 15 or 13 a 14 carbohydrate 14 carbohydrate 15 or 15 or 16 carbohydrate 15 or 17 and 17 and 19 drink 17 and 20 following 18 protein 19 drink 21 each 22 session 23 during 25 wk 24 6 25 wk 25 wk 26 of 26 of 28 training 27 treadmill 28 training a younger untrained group provided a nonexercising comparison . 0 ###LEFT-WALL### 4 group 0 ###LEFT-WALL### 5 provided 0 ###LEFT-WALL### 9 . 1 a 4 group 2 younger 4 group 3 untrained 4 group 4 group 5 provided 5 provided 8 comparison 6 a 8 comparison 7 nonexercising 8 comparison participants were administered heavy water ( ²h₂o [;] deuterium oxide ) continuously for 6 wk to isotopically label newly synthesized skeletal muscle proteins and dna . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 2 were 0 ###LEFT-WALL### 26 . 1 participants 2 were 2 were 5 water 2 were 12 continuously 2 were 13 for 2 were 16 to 3 administered 5 water 4 heavy 5 water 5 water 10 oxide 6 ( 10 oxide 7 ²h₂o 10 oxide 9 deuterium 10 oxide 10 oxide 11 ) 13 for 15 wk 14 6 15 wk 16 to 18 label 17 isotopically 18 label 18 label 22 muscle 18 label 23 proteins 18 label 24 and 19 newly 20 synthesized 20 synthesized 22 muscle 21 skeletal 22 muscle 24 and 25 dna muscle [biopsies] were performed after 6 wk of training . 0 ###LEFT-WALL### 1 muscle 0 ###LEFT-WALL### 4 performed 0 ###LEFT-WALL### 10 . 1 muscle 3 were 3 were 4 performed 4 performed 5 after 5 after 7 wk 6 6 7 wk 7 wk 8 of 8 of 9 training contrary to acute studies , consuming protein after exercise did not increase skeletal muscle protein synthesis rates . 0 ###LEFT-WALL### 6 consuming 0 ###LEFT-WALL### 17 rates 0 ###LEFT-WALL### 18 . 1 contrary 2 to 1 contrary 5 , 1 contrary 6 consuming 2 to 4 studies 3 acute 4 studies 6 consuming 7 protein 6 consuming 8 after 6 consuming 17 rates 8 after 9 exercise 8 after 12 increase 9 exercise 10 did 10 did 11 not 10 did 12 increase 12 increase 16 synthesis 13 skeletal 14 muscle 14 muscle 16 synthesis 15 protein 16 synthesis in contrast , muscle protein synthesis , dna , and phospholipid synthesis were significantly higher in the older exercise groups than the younger sedentary group . 0 ###LEFT-WALL### 1 in 0 ###LEFT-WALL### 13 were 0 ###LEFT-WALL### 26 . 1 in 10 and 1 in 13 were 2 contrast 3 , 3 , 6 synthesis 3 , 7 , 4 muscle 6 synthesis 5 protein 6 synthesis 7 , 8 dna 7 , 10 and 9 , 10 and 10 and 11 phospholipid 12 synthesis 13 were 13 were 15 higher 14 significantly 15 higher 15 higher 16 in 15 higher 21 than 16 in 20 groups 17 the 20 groups 18 older 19 exercise 19 exercise 20 groups 21 than 25 group 22 the 25 group 23 younger 25 group 24 sedentary 25 group the higher dna replication rate could not be attributed to mitochondrial dna and may be due to satellite cell activation . 0 ###LEFT-WALL### 5 rate 0 ###LEFT-WALL### 15 be 0 ###LEFT-WALL### 21 . 1 the 5 rate 2 higher 5 rate 3 dna 5 rate 4 replication 5 rate 5 rate 6 could 6 could 7 not 6 could 13 and 8 be 9 attributed 8 be 13 and 9 attributed 10 to 10 to 12 dna 11 mitochondrial 12 dna 13 and 14 may 14 may 15 be 15 be 17 to 16 due 17 to 17 to 20 activation 18 satellite 20 activation 19 cell 20 activation we conclude that postexercise protein supplementation does not increase rates of mixed protein synthesis over 6 wk and that aerobic exercise may stimulate long - term cell division ( dna synthesis ) in skeletal muscle of humans . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 18 and 0 ###LEFT-WALL### 38 . 1 we 18 and 2 conclude 3 that 2 conclude 18 and 3 that 6 supplementation 3 that 9 increase 4 postexercise 5 protein 5 protein 6 supplementation 6 supplementation 7 does 7 does 8 not 7 does 9 increase 9 increase 10 rates 10 rates 11 of 11 of 14 synthesis 12 mixed 13 protein 13 protein 14 synthesis 14 synthesis 15 over 15 over 17 wk 16 6 17 wk 18 and 23 stimulate 19 that 20 aerobic 20 aerobic 21 exercise 21 exercise 22 may 22 may 23 stimulate 23 stimulate 28 division 23 stimulate 33 in 24 long 25 - 24 long 26 term 26 term 27 cell 27 cell 28 division 28 division 31 synthesis 29 ( 31 synthesis 30 dna 31 synthesis 31 synthesis 32 ) 33 in 35 muscle 34 skeletal 35 muscle 35 muscle 36 of 36 of 37 humans measurements of long - term synthesis rates provide important insights into aging and exercise adaptations . 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 16 . 1 measurements 2 of 1 measurements 13 and 2 of 6 synthesis 3 long 4 - 3 long 5 term 5 term 6 synthesis 6 synthesis 7 rates 6 synthesis 8 provide 7 rates 8 provide 8 provide 10 insights 8 provide 11 into 9 important 10 insights 11 into 12 aging 13 and 15 adaptations 14 exercise 15 adaptations this study is a contribution to the small existing pool of state level research on advanced practice registered nurse ( aprn ) workforce supply . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 is 0 ###LEFT-WALL### 25 . 1 this 2 study 2 study 3 is 3 is 5 contribution 4 a 5 contribution 5 contribution 6 to 5 contribution 11 of 6 to 10 pool 7 the 10 pool 8 small 10 pool 9 existing 10 pool 11 of 14 research 12 state 14 research 13 level 14 research 14 research 15 on 15 on 24 supply 16 advanced 17 practice 17 practice 18 registered 18 registered 19 nurse 19 nurse 21 aprn 20 ( 21 aprn 21 aprn 22 ) 21 aprn 24 supply 23 workforce 24 supply data from four biennial surveys of vermont aprns from 2003 , 2005 , 2007 , [and] 2009 ( n = 1,538 ) were analyzed to produce descriptive statistics of one small state 's aprn demographic , educational , employment , job satisfaction , intention to leave , and practice - setting characteristics . 0 ###LEFT-WALL### 5 surveys 0 ###LEFT-WALL### 24 analyzed 0 ###LEFT-WALL### 53 . 1 data 5 surveys 2 from 3 four 2 from 5 surveys 4 biennial 5 surveys 5 surveys 6 of 5 surveys 23 were 6 of 8 aprns 7 vermont 8 aprns 8 aprns 9 from 8 aprns 12 2005 8 aprns 20 = 9 from 10 2003 11 , 12 2005 12 2005 14 2007 12 2005 15 , 13 , 14 2007 14 2007 15 , 17 2009 20 = 18 ( 20 = 19 n 20 = 20 = 21 1,538 20 = 22 ) 23 were 24 analyzed 24 analyzed 25 to 25 to 26 produce 26 produce 48 and 27 descriptive 28 statistics 28 statistics 29 of 28 statistics 48 and 29 of 42 satisfaction 30 one 32 state 31 small 32 state 32 state 33 's 33 's 42 satisfaction 34 aprn 42 satisfaction 35 demographic 39 employment 35 demographic 40 , 35 demographic 41 job 36 , 39 employment 37 educational 38 , 37 educational 39 employment 39 employment 40 , 41 job 42 satisfaction 42 satisfaction 44 intention 43 , 44 intention 44 intention 45 to 44 intention 46 leave 44 intention 47 , 45 to 46 leave 48 and 49 practice 48 and 50 - 48 and 51 setting 51 setting 52 characteristics survey results were then used to identify patterns or trends that existed in the data . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 5 used 0 ###LEFT-WALL### 16 . 1 survey 2 results 2 results 3 were 3 were 5 used 4 then 5 used 5 used 6 to 5 used 7 identify 6 to 7 identify 7 identify 9 or 8 patterns 9 or 9 or 10 trends 9 or 11 that 9 or 12 existed 11 that 12 existed 12 existed 13 in 13 in 15 data 14 the 15 data there was a marked shift in the employment settings and a decrease time worked as an aprn , despite an aging aprn workforce . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 was 1 there 2 was 2 was 5 shift 3 a 5 shift 4 marked 5 shift 5 shift 6 in 5 shift 14 worked 6 in 10 and 7 the 9 settings 8 employment 9 settings 9 settings 10 and 10 and 13 time 11 a 13 time 12 decrease 13 time 14 worked 15 as 14 worked 19 despite 15 as 17 aprn 16 an 17 aprn 18 , 19 despite 19 despite 23 workforce 19 despite 24 . 20 an 23 workforce 21 aging 23 workforce 22 aprn 23 workforce there was an increase in the aggregate education level of aprns ; however , the percentage educated at the doctoral level remained flat at 2 % . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 was 0 ###LEFT-WALL### 12 ; 0 ###LEFT-WALL### 27 . 1 there 2 was 2 was 4 increase 3 an 4 increase 4 increase 5 in 4 increase 10 of 5 in 9 level 6 the 9 level 7 aggregate 8 education 8 education 9 level 10 of 11 aprns 12 ; 16 percentage 12 ; 22 remained 13 however 14 , 13 however 16 percentage 15 the 16 percentage 16 percentage 17 educated 16 percentage 22 remained 17 educated 18 at 18 at 21 level 19 the 21 level 20 doctoral 21 level 22 remained 23 flat 23 flat 24 at 24 at 26 % 25 2 26 % overall , aprns were a satisfied segment of the health workforce ; however , those intending to leave for dissatisfaction voiced more concern about job stress and less concern about salary and benefits over time . 0 ###LEFT-WALL### 3 aprns 0 ###LEFT-WALL### 4 were 0 ###LEFT-WALL### 12 ; 0 ###LEFT-WALL### 36 . 1 overall 2 , 1 overall 3 aprns 3 aprns 4 were 4 were 7 segment 5 a 7 segment 6 satisfied 7 segment 7 segment 8 of 8 of 11 workforce 9 the 11 workforce 10 health 11 workforce 12 ; 15 those 12 ; 21 voiced 13 however 14 , 13 however 15 those 15 those 16 intending 15 those 19 for 15 those 21 voiced 16 intending 17 to 16 intending 18 leave 17 to 18 leave 19 for 20 dissatisfaction 21 voiced 23 concern 21 voiced 24 about 21 voiced 30 about 22 more 23 concern 24 about 27 and 25 job 26 stress 26 stress 27 and 27 and 29 concern 28 less 29 concern 30 about 32 and 31 salary 32 and 32 and 33 benefits 32 and 34 over 34 over 35 time implications for workforce planning and public policy are discussed . 0 ###LEFT-WALL### 1 implications 0 ###LEFT-WALL### 9 discussed 0 ###LEFT-WALL### 10 . 1 implications 2 for 1 implications 8 are 2 for 5 and 3 workforce 4 planning 4 planning 5 and 5 and 7 policy 6 public 7 policy 8 are 9 discussed ercc1 - xpf is a structure - specific endonuclease required for nucleotide excision repair , interstrand [crosslink] repair , and the repair of some double - strand breaks . 0 ###LEFT-WALL### 3 xpf 0 ###LEFT-WALL### 4 is 0 ###LEFT-WALL### 7 - 0 ###LEFT-WALL### 29 . 1 ercc1 3 xpf 2 - 3 xpf 3 xpf 4 is 4 is 6 structure 5 a 6 structure 7 - 20 and 8 specific 9 endonuclease 9 endonuclease 10 required 9 endonuclease 11 for 9 endonuclease 20 and 11 for 14 repair 12 nucleotide 14 repair 13 excision 14 repair 14 repair 18 repair 15 , 18 repair 16 interstrand 18 repair 18 repair 19 , 19 , 20 and 20 and 22 repair 20 and 23 of 21 the 22 repair 23 of 28 breaks 24 some 28 breaks 25 double 26 - 25 double 27 strand 27 strand 28 breaks mutations in ercc1 or xpf cause xeroderma pigmentosum , xfe progeroid syndrome or cerebro - oculo - facio - skeletal syndrome , characterized by increased risk of cancer , accelerated aging and severe developmental abnormalities , respectively . 0 ###LEFT-WALL### 1 mutations 0 ###LEFT-WALL### 30 accelerated 1 mutations 2 in 1 mutations 30 accelerated 2 in 13 or 3 ercc1 4 or 4 or 8 pigmentosum 4 or 9 , 5 xpf 7 xeroderma 6 cause 7 xeroderma 7 xeroderma 8 pigmentosum 9 , 12 syndrome 9 , 13 or 10 xfe 11 progeroid 11 progeroid 12 syndrome 13 or 21 syndrome 13 or 23 characterized 14 cerebro 15 - 14 cerebro 21 syndrome 16 oculo 18 facio 16 oculo 21 syndrome 17 - 18 facio 18 facio 19 - 20 skeletal 21 syndrome 22 , 23 characterized 23 characterized 24 by 23 characterized 29 , 24 by 26 risk 25 increased 26 risk 26 risk 27 of 27 of 28 cancer 30 accelerated 35 abnormalities 30 accelerated 37 respectively 31 aging 32 and 32 and 33 severe 32 and 35 abnormalities 34 developmental 35 abnormalities 36 , 37 respectively 37 respectively 38 . this review provides a comprehensive overview of the health impact of ercc1 - xpf deficiency , based on these rare diseases and mouse models of them . 0 ###LEFT-WALL### 2 review 0 ###LEFT-WALL### 16 , 0 ###LEFT-WALL### 27 . 1 this 2 review 2 review 16 , 3 provides 6 overview 3 provides 16 , 4 a 5 comprehensive 4 a 6 overview 5 comprehensive 6 overview 6 overview 7 of 7 of 10 impact 8 the 10 impact 9 health 10 impact 10 impact 11 of 11 of 15 deficiency 12 ercc1 14 xpf 13 - 14 xpf 14 xpf 15 deficiency 16 , 17 based 16 , 18 on 18 on 22 and 19 these 21 diseases 20 rare 21 diseases 21 diseases 22 and 22 and 24 models 22 and 25 of 23 mouse 24 models 25 of 26 them this offers an understanding of the tremendous health impact of dna damage derived from environmental and endogenous sources . 0 ###LEFT-WALL### 1 this 0 ###LEFT-WALL### 2 offers 0 ###LEFT-WALL### 19 . 1 this 2 offers 2 offers 4 understanding 2 offers 9 impact 2 offers 14 from 3 an 4 understanding 4 understanding 5 of 5 of 8 health 6 the 8 health 7 tremendous 8 health 9 impact 10 of 10 of 12 damage 11 dna 12 damage 12 damage 13 derived 14 from 18 sources 15 environmental 16 and 16 and 17 endogenous 16 and 18 sources ageing of human skin may result from [both] the passage of time ( intrinsic ageing ) and from cumulative exposure to external influences ( extrinsic ageing ) such as ultraviolet radiation ( uvr [ )(which promote wrinkle formation and loss of tissue elasticity . 0 ###LEFT-WALL### 1 ageing 0 ###LEFT-WALL### 6 result 1 ageing 2 of 1 ageing 5 may 2 of 4 skin 3 human 4 skin 5 may 6 result 6 result 17 and 6 result 21 to 6 result 29 as 7 from 10 passage 7 from 17 and 9 the 10 passage 10 passage 11 of 11 of 12 time 12 time 15 ageing 13 ( 15 ageing 14 intrinsic 15 ageing 15 ageing 16 ) 17 and 18 from 18 from 20 exposure 19 cumulative 20 exposure 21 to 23 influences 22 external 23 influences 23 influences 26 ageing 24 ( 26 ageing 25 extrinsic 26 ageing 26 ageing 27 ) 28 such 29 as 29 as 31 radiation 30 ultraviolet 31 radiation 31 radiation 33 uvr 32 ( 33 uvr 33 uvr 35 )(which 33 uvr 36 promote 33 uvr 44 . 35 )(which 36 promote 36 promote 39 and 37 wrinkle 38 formation 38 formation 39 and 39 and 40 loss 39 and 41 of 41 of 43 elasticity 42 tissue 43 elasticity whilst both ageing processes are associated with phenotypic changes in cutaneous cells , the major functional manifestations of ageing occur as a consequence of structural and compositional remodeling of normally long [-] lived dermal extracellular matrix proteins . 0 ###LEFT-WALL### 15 major 0 ###LEFT-WALL### 33 lived 0 ###LEFT-WALL### 38 . 1 whilst 4 processes 1 whilst 6 associated 1 whilst 13 , 1 whilst 15 major 2 both 4 processes 3 ageing 4 processes 4 processes 5 are 5 are 6 associated 6 associated 7 with 6 associated 10 in 7 with 9 changes 8 phenotypic 9 changes 10 in 12 cells 11 cutaneous 12 cells 14 the 15 major 15 major 17 manifestations 15 major 29 of 15 major 33 lived 16 functional 17 manifestations 17 manifestations 18 of 17 manifestations 20 occur 18 of 19 ageing 20 occur 21 as 21 as 23 consequence 22 a 23 consequence 23 consequence 24 of 23 consequence 29 of 24 of 28 remodeling 25 structural 26 and 26 and 27 compositional 26 and 28 remodeling 30 normally 33 lived 31 long 33 lived 33 lived 37 proteins 34 dermal 36 matrix 35 extracellular 36 matrix 36 matrix 37 proteins this review briefly considers the effects of ageing on dermal collagens and proteoglycans before focusing on the mechanisms , functional consequences and treatment of elastic fibre remodeling in ageing skin . 0 ###LEFT-WALL### 22 and 0 ###LEFT-WALL### 31 . 1 this 2 review 2 review 12 and 2 review 19 , 3 briefly 4 considers 4 considers 6 effects 4 considers 9 on 4 considers 12 and 5 the 6 effects 6 effects 7 of 7 of 8 ageing 9 on 11 collagens 10 dermal 11 collagens 12 and 13 proteoglycans 12 and 14 before 14 before 15 focusing 15 focusing 16 on 16 on 18 mechanisms 17 the 18 mechanisms 19 , 21 consequences 19 , 22 and 20 functional 21 consequences 22 and 23 treatment 22 and 24 of 22 and 27 remodeling 24 of 26 fibre 25 elastic 26 fibre 27 remodeling 28 in 27 remodeling 30 skin 28 in 29 ageing the early stages of photoageing are characterised by the differential degradation of elastic fibre proteins and whilst the activity of extracellular matrix proteases is increased in photoexposed skin , the substrate specificity of these enzymes is low . 0 ###LEFT-WALL### 3 stages 0 ###LEFT-WALL### 7 characterised 0 ###LEFT-WALL### 16 and 0 ###LEFT-WALL### 38 . 1 the 3 stages 2 early 3 stages 3 stages 4 of 3 stages 6 are 4 of 5 photoageing 6 are 7 characterised 7 characterised 8 by 8 by 11 degradation 9 the 11 degradation 10 differential 11 degradation 11 degradation 12 of 12 of 15 proteins 13 elastic 14 fibre 14 fibre 15 proteins 16 and 32 specificity 16 and 36 is 17 whilst 19 activity 17 whilst 25 increased 17 whilst 29 , 17 whilst 32 specificity 18 the 19 activity 19 activity 20 of 19 activity 24 is 20 of 23 proteases 21 extracellular 22 matrix 22 matrix 23 proteases 24 is 25 increased 25 increased 26 in 26 in 28 skin 27 photoexposed 28 skin 30 the 32 specificity 31 substrate 32 specificity 32 specificity 33 of 32 specificity 36 is 33 of 35 enzymes 34 these 35 enzymes 36 is 37 low we have recently shown however , that isolated fibrillin microfibrils are susceptible to direct degradation by physiologically attainable doses of uv - [b] radiation and that elastic fibre proteins as a group are highly enriched in uv - absorbing amino acid residues . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 14 direct 0 ###LEFT-WALL### 22 - 1 we 2 have 2 have 4 shown 3 recently 4 shown 4 shown 7 that 4 shown 11 are 5 however 6 , 5 however 7 that 7 that 8 isolated 8 isolated 9 fibrillin 10 microfibrils 11 are 11 are 12 susceptible 12 susceptible 13 to 12 susceptible 14 direct 13 to 14 direct 14 direct 15 degradation 14 direct 16 by 16 by 19 doses 17 physiologically 18 attainable 18 attainable 19 doses 19 doses 20 of 20 of 21 uv 22 - 24 radiation 22 - 25 and 25 and 29 proteins 25 and 35 enriched 26 that 27 elastic 27 elastic 29 proteins 28 fibre 29 proteins 29 proteins 30 as 29 proteins 33 are 30 as 32 group 31 a 32 group 33 are 35 enriched 34 highly 35 enriched 35 enriched 36 in 35 enriched 39 absorbing 36 in 37 uv 38 - 39 absorbing 39 absorbing 42 residues 39 absorbing 43 . 40 amino 41 acid 41 acid 42 residues functionally , elastic fibre remodeling events may adversely impact [on] : the mechanical properties of tissues , the recruitment and activation of immune cells , the expression of matrix metalloproteinases and cytokine signaling ( by perturbing fibrillin microfibril sequestration of tgfβ ) . 0 ###LEFT-WALL### 3 elastic 0 ###LEFT-WALL### 11 : 0 ###LEFT-WALL### 17 , 0 ###LEFT-WALL### 43 . 1 functionally 2 , 1 functionally 3 elastic 3 elastic 4 fibre 3 elastic 9 impact 3 elastic 11 : 4 fibre 5 remodeling 4 fibre 7 may 5 remodeling 6 events 7 may 9 impact 8 adversely 9 impact 11 : 14 properties 12 the 14 properties 13 mechanical 14 properties 14 properties 15 of 15 of 16 tissues 17 , 20 and 18 the 19 recruitment 19 recruitment 20 and 20 and 21 activation 20 and 22 of 20 and 31 and 22 of 24 cells 23 immune 24 cells 25 , 31 and 26 the 27 expression 27 expression 28 of 27 expression 31 and 28 of 30 metalloproteinases 29 matrix 30 metalloproteinases 31 and 32 cytokine 31 and 33 signaling 31 and 35 by 31 and 42 ) 34 ( 35 by 35 by 36 perturbing 35 by 42 ) 36 perturbing 39 sequestration 37 fibrillin 38 microfibril 38 microfibril 39 sequestration 39 sequestration 40 of 40 of 41 tgfβ finally , newly developed topical interventions appear to be capable of regenerating elements of the elastic fibre system in ageing skin , whilst systemic treatments may potentially prevent the pathological tissue remodeling events which occur in response to elastic fibre degradation . 0 ###LEFT-WALL### 6 interventions 0 ###LEFT-WALL### 7 appear 0 ###LEFT-WALL### 22 , 0 ###LEFT-WALL### 42 . 1 finally 2 , 1 finally 6 interventions 3 newly 4 developed 4 developed 6 interventions 5 topical 6 interventions 6 interventions 7 appear 7 appear 8 to 7 appear 9 be 8 to 9 be 9 be 10 capable 10 capable 11 of 11 of 12 regenerating 12 regenerating 13 elements 12 regenerating 19 in 13 elements 14 of 14 of 18 system 15 the 18 system 16 elastic 17 fibre 17 fibre 18 system 19 in 21 skin 20 ageing 21 skin 22 , 25 treatments 22 , 28 prevent 23 whilst 24 systemic 23 whilst 25 treatments 25 treatments 26 may 26 may 28 prevent 27 potentially 28 prevent 28 prevent 31 tissue 28 prevent 38 to 29 the 31 tissue 30 pathological 31 tissue 31 tissue 32 remodeling 32 remodeling 33 events 33 events 34 which 33 events 35 occur 34 which 35 occur 35 occur 37 response 36 in 37 response 38 to 41 degradation 39 elastic 40 fibre 40 fibre 41 degradation background and objective : to determine the association between frailty and mortality , dysfunctionality , [falls] and hospitalizations in the mexican health and aging study . 0 ###LEFT-WALL### 3 objective 0 ###LEFT-WALL### 4 : 0 ###LEFT-WALL### 26 . 1 background 2 and 2 and 3 objective 4 : 5 to 4 : 6 determine 5 to 6 determine 6 determine 8 association 7 the 8 association 8 association 9 between 9 between 23 and 10 frailty 11 and 11 and 12 mortality 11 and 13 , 13 , 14 dysfunctionality 13 , 17 and 15 , 17 and 17 and 18 hospitalizations 17 and 19 in 17 and 23 and 19 in 22 health 20 the 21 mexican 21 mexican 22 health 23 and 25 study 24 aging 25 study frail subjects were considered when they had at least two conditions . 0 ###LEFT-WALL### 2 subjects 0 ###LEFT-WALL### 4 considered 0 ###LEFT-WALL### 12 . 1 frail 2 subjects 2 subjects 3 were 3 were 4 considered 4 considered 5 when 5 when 6 they 5 when 7 had 6 they 7 had 7 had 11 conditions 8 at 9 least 9 least 10 two 10 two 11 conditions the robust group was considered when they had zero conditions . 0 ###LEFT-WALL### 3 group 0 ###LEFT-WALL### 5 considered 0 ###LEFT-WALL### 11 . 1 the 3 group 2 robust 3 group 3 group 4 was 4 was 5 considered 5 considered 6 when 5 considered 10 conditions 6 when 7 they 6 when 8 had 7 they 8 had 8 had 9 zero pre - frail or intermediate were those with one condition . 0 ###LEFT-WALL### 4 or 0 ###LEFT-WALL### 6 were 0 ###LEFT-WALL### 11 . 1 pre 2 - 1 pre 4 or 3 frail 4 or 4 or 5 intermediate 4 or 6 were 6 were 7 those 7 those 8 with 8 with 10 condition 9 one 10 condition mortality , hospitalizations , falls , and functional dependency were evaluated during 2003 ( [second] [wave] of the study ) . 0 ###LEFT-WALL### 1 mortality 0 ###LEFT-WALL### 5 falls 0 ###LEFT-WALL### 7 and 0 ###LEFT-WALL### 21 . 1 mortality 3 hospitalizations 1 mortality 5 falls 2 , 3 hospitalizations 3 hospitalizations 4 , 6 , 7 and 7 and 9 dependency 7 and 11 evaluated 8 functional 9 dependency 9 dependency 10 were 10 were 11 evaluated 11 evaluated 12 during 12 during 13 2003 13 2003 17 of 14 ( 17 of 17 of 19 study 17 of 20 ) 18 the 19 study relative risk was calculated for each complication , as well as hazard [ratio] and odds ratio through cox regression model ( for mortality ) and logistic regression ( for the rest of the complications ) respectively , adjusted for covariates . 0 ###LEFT-WALL### 2 risk 0 ###LEFT-WALL### 37 , 0 ###LEFT-WALL### 41 . 1 relative 2 risk 2 risk 37 , 3 was 4 calculated 3 was 37 , 4 calculated 5 for 4 calculated 36 respectively 5 for 7 complication 6 each 7 complication 7 complication 11 as 8 , 11 as 9 as 10 well 10 well 11 as 11 as 25 and 11 as 35 ) 12 hazard 14 and 14 and 16 ratio 14 and 17 through 14 and 25 and 15 odds 16 ratio 17 through 20 model 18 cox 19 regression 19 regression 20 model 20 model 22 for 21 ( 22 for 22 for 23 mortality 22 for 24 ) 25 and 27 regression 25 and 29 for 26 logistic 27 regression 28 ( 29 for 29 for 34 complications 29 for 35 ) 30 the 31 rest 31 rest 32 of 31 rest 34 complications 32 of 34 complications 33 the 34 complications 37 , 38 adjusted 37 , 39 for 39 for 40 covariates results : the states of frailty and pre - frailty were independently associated with mortality , hazard [ratio] of 1.61 ( ci [95] [%] 1.01 - 2.55 ) and 1.94 [(] ci 95 % 1.20 - 3.13 ) , respectively . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 4 states 2 : 13 associated 3 the 4 states 4 states 5 of 4 states 13 associated 5 of 7 and 6 frailty 7 and 7 and 8 pre 7 and 9 - 7 and 10 frailty 7 and 11 were 10 frailty 11 were 11 were 12 independently 13 associated 14 with 13 associated 35 1.20 13 associated 40 respectively 14 with 29 and 14 with 34 % 15 mortality 16 , 16 , 17 hazard 16 , 29 and 17 hazard 19 of 19 of 20 1.61 20 1.61 22 ci 21 ( 22 ci 22 ci 26 - 22 ci 28 ) 25 1.01 26 - 26 - 27 2.55 29 and 32 ci 30 1.94 32 ci 33 95 34 % 35 1.20 37 3.13 36 - 37 3.13 37 3.13 38 ) 39 , 40 respectively 40 respectively 41 . only the state of frailty was independently associated with hospitalization and functional dependence [,] odds ratio of 1.53 [(] ci 95 % 1.13 - 2.07 [ )(and 3.07 ( ci [95] [%] 1.76 - 5.34 ) . 0 ###LEFT-WALL### 1 only 0 ###LEFT-WALL### 8 associated 0 ###LEFT-WALL### 37 . 1 only 3 state 2 the 3 state 3 state 4 of 3 state 6 was 4 of 5 frailty 6 was 8 associated 7 independently 8 associated 8 associated 9 with 9 with 22 % 9 with 23 1.13 10 hospitalization 11 and 11 and 16 ratio 11 and 17 of 11 and 22 % 12 functional 13 dependence 13 dependence 16 ratio 15 odds 16 ratio 17 of 20 ci 18 1.53 20 ci 20 ci 21 95 23 1.13 27 )(and 24 - 27 )(and 25 2.07 27 )(and 27 )(and 28 3.07 27 )(and 30 ci 27 )(and 36 ) 29 ( 30 ci 30 ci 34 - 30 ci 36 ) 33 1.76 34 - 34 - 35 5.34 there was no association between pre - frailty or frailty [with] falls . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 was 0 ###LEFT-WALL### 9 or 0 ###LEFT-WALL### 13 . 1 there 2 was 2 was 4 association 3 no 4 association 4 association 5 between 5 between 8 frailty 6 pre 7 - 6 pre 8 frailty 9 or 10 frailty 9 or 12 falls 10 frailty 12 falls conclusion : frailty is associated with an increase in the rate of mortality , hospitalizations and dependence in basic activities of daily life . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 24 . 2 : 3 frailty 2 : 5 associated 3 frailty 4 is 4 is 5 associated 5 associated 6 with 5 associated 9 in 5 associated 18 in 6 with 8 increase 7 an 8 increase 9 in 16 and 10 the 11 rate 11 rate 12 of 11 rate 14 , 12 of 13 mortality 14 , 15 hospitalizations 14 , 16 and 16 and 17 dependence 18 in 20 activities 19 basic 20 activities 20 activities 21 of 21 of 23 life 22 daily 23 life long - living individuals ( llis ) are used to study exceptional longevity . 0 ###LEFT-WALL### 4 individuals 0 ###LEFT-WALL### 9 used 0 ###LEFT-WALL### 14 . 1 long 2 - 1 long 3 living 3 living 4 individuals 4 individuals 6 llis 4 individuals 8 are 5 ( 6 llis 6 llis 7 ) 8 are 9 used 9 used 10 to 9 used 11 study 10 to 11 study 11 study 13 longevity 12 exceptional 13 longevity a number of genetic variants have been found [associated] in llis to date , but further identification of variants would improve knowledge on the mechanisms regulating the rate of aging . 0 ###LEFT-WALL### 2 number 0 ###LEFT-WALL### 15 but 0 ###LEFT-WALL### 31 . 1 a 2 number 2 number 3 of 2 number 15 but 3 of 5 variants 4 genetic 5 variants 6 have 7 been 6 have 15 but 7 been 8 found 8 found 10 in 8 found 13 date 10 in 11 llis 12 to 13 date 14 , 15 but 15 but 21 improve 16 further 17 identification 17 identification 18 of 17 identification 20 would 18 of 19 variants 20 would 21 improve 21 improve 22 knowledge 21 improve 23 on 23 on 25 mechanisms 24 the 25 mechanisms 25 mechanisms 26 regulating 25 mechanisms 29 of 26 regulating 28 rate 27 the 28 rate 29 of 30 aging therefore , we performed a genome - wide association study on 410 llis and 553 young control individuals with a 317 k single - nucleotide polymorphism ( snp ) chip to identify novel traits associated with aging . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 7 - 0 ###LEFT-WALL### 32 identify 0 ###LEFT-WALL### 38 . 1 therefore 2 , 1 therefore 3 we 3 we 4 performed 4 performed 6 genome 5 a 6 genome 7 - 14 and 7 - 30 chip 8 wide 9 association 9 association 10 study 10 study 11 on 10 study 14 and 11 on 13 llis 12 410 13 llis 14 and 18 individuals 14 and 19 with 14 and 28 snp 14 and 30 chip 15 553 18 individuals 16 young 17 control 17 control 18 individuals 19 with 26 polymorphism 20 a 26 polymorphism 21 317 22 k 22 k 26 polymorphism 23 single 24 - 23 single 25 nucleotide 25 nucleotide 26 polymorphism 27 ( 28 snp 28 snp 29 ) 30 chip 31 to 31 to 32 identify 32 identify 34 traits 32 identify 36 with 33 novel 34 traits 34 traits 35 associated 36 with 37 aging among the top ( p < 1 × 10 ( - 4 [ )( ( initially identified , [we] found rs10491334 ( camkiv ) [(] odds ratio [ or ] = [0.55] [;] [95] [%] [confidence] [interval] [ ci []] 0.42 - 0.73 [;] p = 2.88 × 10 ( - 5 ) [ )(, a variant previously reported associated with diastolic blood pressure , associated also in a replication set of 116 [llis] and 160 controls ( or [=] 0.54 [;] 95 % ci 0.32 - 0.90 [;] p = 9 × 10 ( - 3 ) [ )( 1 among 3 top 1 among 8 × 2 the 3 top 3 top 6 < 4 ( 6 < 5 p 6 < 6 < 7 1 8 × 9 10 8 × 12 4 8 × 18 , 10 ( 12 4 11 - 12 4 12 4 14 )( 16 initially 17 identified 17 identified 18 , 18 , 20 found 18 , 26 odds 21 rs10491334 23 camkiv 21 rs10491334 24 ) 21 rs10491334 26 odds 22 ( 23 camkiv 23 camkiv 24 ) 26 odds 27 ratio 26 odds 31 = 27 ratio 29 or 27 ratio 31 = 28 [ 29 or 29 or 30 ] 31 = 42 - 38 [ 42 - 39 ci 41 0.42 39 ci 42 - 42 - 43 0.73 43 0.73 46 = 45 p 46 = 46 = 48 × 47 2.88 48 × 48 × 49 10 48 × 60 associated 49 10 52 5 49 10 60 associated 50 ( 52 5 51 - 52 5 52 5 53 ) 55 )(, 59 reported 56 a 57 variant 57 variant 59 reported 58 previously 59 reported 59 reported 60 associated 60 associated 61 with 61 with 64 pressure 62 diastolic 64 pressure 63 blood 64 pressure 64 pressure 66 associated 65 , 66 associated 66 associated 67 also 66 associated 68 in 68 in 71 set 69 a 71 set 70 replication 71 set 71 set 72 of 72 of 77 controls 73 116 75 and 75 and 76 160 75 and 77 controls 77 controls 85 ci 77 controls 88 0.90 78 ( 85 ci 79 or 81 0.54 79 or 85 ci 83 95 85 ci 84 % 85 ci 85 ci 86 0.32 85 ci 87 - 87 - 88 0.90 88 0.90 91 = 88 0.90 100 )( 90 p 91 = 91 = 93 × 92 9 93 × 93 × 94 10 93 × 97 3 95 ( 97 3 96 - 97 3 97 3 98 ) furthermore , in vitro analysis established that calcium/calmodulin - dependent protein kinase iv ( camkiv ) activates the survival proteins akt , sirt1 , and foxo3a , and we found that homozygous carriers of rs10491334 have a significant reduction in camkiv expression . 0 ###LEFT-WALL### 5 analysis 0 ###LEFT-WALL### 6 established 0 ###LEFT-WALL### 25 and 0 ###LEFT-WALL### 43 . 1 furthermore 2 , 1 furthermore 5 analysis 3 in 4 vitro 4 vitro 5 analysis 5 analysis 6 established 6 established 7 that 7 that 8 calcium/calmodulin 7 that 17 activates 8 calcium/calmodulin 13 iv 8 calcium/calmodulin 17 activates 9 - 13 iv 10 dependent 12 kinase 11 protein 12 kinase 12 kinase 13 iv 13 iv 15 camkiv 13 iv 16 ) 14 ( 15 camkiv 15 camkiv 16 ) 17 activates 21 akt 18 the 20 proteins 19 survival 20 proteins 20 proteins 21 akt 21 akt 23 sirt1 22 , 23 sirt1 23 sirt1 24 , 24 , 25 and 25 and 28 and 25 and 30 found 26 foxo3a 28 and 27 , 28 and 28 and 29 we 28 and 30 found 30 found 31 that 31 that 33 carriers 31 that 36 have 32 homozygous 33 carriers 33 carriers 34 of 33 carriers 36 have 34 of 35 rs10491334 36 have 39 reduction 36 have 40 in 37 a 39 reduction 38 significant 39 reduction 40 in 42 expression 41 camkiv 42 expression this , together [with] [the] observed reduction in minor - allele carriers among centenarians , points to a detrimental role for the snp . 0 ###LEFT-WALL### 1 this 0 ###LEFT-WALL### 16 points 0 ###LEFT-WALL### 24 . 1 this 16 points 2 , 6 observed 3 together 6 observed 6 observed 7 reduction 6 observed 8 in 6 observed 13 among 6 observed 15 , 6 observed 16 points 8 in 12 carriers 9 minor 10 - 9 minor 12 carriers 11 allele 12 carriers 13 among 14 centenarians 16 points 17 to 16 points 21 for 17 to 20 role 18 a 19 detrimental 18 a 20 role 19 detrimental 20 role 21 for 23 snp 22 the 23 snp in conclusion , prolongevity genes are activated by camkiv , the levels of which are influenced by rs10491334 , a snp associated with human longevity . 0 ###LEFT-WALL### 2 conclusion 0 ###LEFT-WALL### 3 , 0 ###LEFT-WALL### 26 . 1 in 2 conclusion 3 , 5 genes 3 , 7 activated 3 , 19 , 4 prolongevity 5 genes 5 genes 6 are 6 are 7 activated 7 activated 8 by 8 by 9 camkiv 9 camkiv 12 levels 10 , 12 levels 11 the 12 levels 12 levels 13 of 12 levels 19 , 13 of 14 which 13 of 16 influenced 14 which 15 are 15 are 16 influenced 16 influenced 17 by 17 by 18 rs10491334 19 , 21 snp 19 , 22 associated 20 a 21 snp 21 snp 22 associated 22 associated 23 with 23 with 25 longevity 24 human 25 longevity ischemic [stroke] is emerging as a major health problem for elderly women . 0 ###LEFT-WALL### 1 ischemic 0 ###LEFT-WALL### 3 is 0 ###LEFT-WALL### 13 . 1 ischemic 3 is 3 is 4 emerging 4 emerging 5 as 5 as 9 problem 6 a 9 problem 7 major 9 problem 8 health 9 problem 9 problem 10 for 10 for 12 women 11 elderly 12 women women have lower stroke incidence [than] men until an advanced age , when the epidemiology of ischemic stroke shifts and incidence rises dramatically in women . 0 ###LEFT-WALL### 1 women 0 ###LEFT-WALL### 2 have 1 women 2 have 2 have 7 men 2 have 8 until 2 have 13 when 3 lower 4 stroke 4 stroke 7 men 5 incidence 7 men 8 until 11 age 9 an 10 advanced 9 an 11 age 10 advanced 11 age 12 , 13 when 13 when 15 epidemiology 13 when 22 rises 13 when 26 . 14 the 15 epidemiology 15 epidemiology 16 of 15 epidemiology 22 rises 16 of 20 and 17 ischemic 18 stroke 18 stroke 19 shifts 19 shifts 20 and 20 and 21 incidence 22 rises 23 dramatically 22 rises 24 in 24 in 25 women experimental models [of] rodent stroke [have] replicated this clinical epidemiology , with exacerbated injury in older compared [with] young female rodents . 0 ###LEFT-WALL### 1 experimental 0 ###LEFT-WALL### 2 models 1 experimental 2 models 2 models 10 epidemiology 2 models 12 with 4 rodent 7 replicated 5 stroke 7 replicated 7 replicated 10 epidemiology 8 this 9 clinical 9 clinical 10 epidemiology 11 , 12 with 12 with 14 injury 12 with 22 . 13 exacerbated 14 injury 14 injury 15 in 15 in 21 rodents 16 older 21 rodents 17 compared 21 rodents 19 young 21 rodents 20 female 21 rodents many of the detrimental effects of aging on ischemic stroke outcome [in] females can be replicated by ovariectomy , suggesting that hormones such as estrogen play a neuroprotective role . 0 ###LEFT-WALL### 15 be 1 many 2 of 1 many 5 effects 2 of 5 effects 3 the 5 effects 4 detrimental 5 effects 5 effects 6 of 5 effects 14 can 6 of 7 aging 7 aging 8 on 8 on 13 females 9 ischemic 10 stroke 10 stroke 11 outcome 11 outcome 13 females 14 can 15 be 15 be 16 replicated 16 replicated 17 by 16 replicated 20 suggesting 17 by 18 ovariectomy 19 , 20 suggesting 20 suggesting 21 that 20 suggesting 30 . 21 that 22 hormones 21 that 26 play 22 hormones 24 as 23 such 24 as 24 as 25 estrogen 26 play 29 role 27 a 28 neuroprotective 27 a 29 role 28 neuroprotective 29 role however , emerging data suggest that the molecular mechanisms leading to ischemic cell death differ in the two sexes , and these effects may be independent of circulating hormone levels . 0 ###LEFT-WALL### 4 data 0 ###LEFT-WALL### 5 suggest 0 ###LEFT-WALL### 31 . 1 however 2 , 1 however 4 data 3 emerging 4 data 4 data 5 suggest 5 suggest 6 that 6 that 9 mechanisms 6 that 15 differ 7 the 9 mechanisms 8 molecular 9 mechanisms 9 mechanisms 10 leading 10 leading 11 to 11 to 14 death 12 ischemic 14 death 13 cell 14 death 15 differ 16 in 16 in 26 independent 17 the 26 independent 18 two 19 sexes 19 sexes 21 and 20 , 21 and 21 and 22 these 21 and 23 effects 21 and 25 be 21 and 26 independent 23 effects 24 may 24 may 25 be 26 independent 27 of 27 of 28 circulating 28 circulating 30 levels 29 hormone 30 levels this article highlights recent clinical and experimental literature on sex differences in stroke outcomes and mechanisms . 0 ###LEFT-WALL### 2 article 0 ###LEFT-WALL### 3 highlights 0 ###LEFT-WALL### 17 . 1 this 2 article 2 article 3 highlights 3 highlights 8 literature 3 highlights 9 on 3 highlights 12 in 4 recent 8 literature 5 clinical 6 and 6 and 7 experimental 6 and 8 literature 9 on 11 differences 10 sex 11 differences 12 in 15 and 13 stroke 14 outcomes 14 outcomes 15 and 15 and 16 mechanisms national data from the asia [-] pacific region suggest that stroke accounts for over 10 % of female deaths . 0 ###LEFT-WALL### 2 data 0 ###LEFT-WALL### 9 suggest 0 ###LEFT-WALL### 20 . 1 national 2 data 2 data 3 from 2 data 9 suggest 3 from 8 region 4 the 8 region 5 asia 7 pacific 7 pacific 8 region 9 suggest 10 that 9 suggest 11 stroke 11 stroke 12 accounts 12 accounts 13 for 13 for 16 % 14 over 15 10 15 10 16 % 16 % 17 of 17 of 19 deaths 18 female 19 deaths with general aging in the region , and longer life expectancies for women than men , action is required to maintain recent improvements in female death rates [from] stroke . 0 ###LEFT-WALL### 17 action 0 ###LEFT-WALL### 19 required 0 ###LEFT-WALL### 30 . 1 with 11 expectancies 1 with 14 than 1 with 15 men 1 with 16 , 1 with 17 action 2 general 3 aging 2 general 8 and 3 aging 4 in 4 in 6 region 5 the 6 region 7 , 8 and 8 and 9 longer 8 and 10 life 10 life 11 expectancies 11 expectancies 12 for 12 for 13 women 17 action 18 is 18 is 19 required 19 required 20 to 19 required 21 maintain 20 to 21 maintain 21 maintain 23 improvements 21 maintain 24 in 22 recent 23 improvements 24 in 26 death 25 female 26 death 26 death 27 rates 26 death 29 stroke 27 rates 29 stroke however , local data on incidence [and] risk factors for stroke [amongst] women are scarce . 0 ###LEFT-WALL### 4 data 0 ###LEFT-WALL### 14 are 0 ###LEFT-WALL### 16 . 1 however 2 , 1 however 4 data 3 local 4 data 4 data 5 on 4 data 14 are 5 on 9 factors 6 incidence 9 factors 8 risk 9 factors 9 factors 10 for 10 for 13 women 11 stroke 13 women 14 are 15 scarce data from 214,032 women in the asia pacific cohort studies collaboration were thus used to investigate the risk factors [for] stroke in the region . 0 ###LEFT-WALL### 1 data 0 ###LEFT-WALL### 14 used 0 ###LEFT-WALL### 25 . 1 data 2 from 1 data 12 were 2 from 4 women 3 214,032 4 women 4 women 5 in 5 in 11 collaboration 6 the 11 collaboration 7 asia 8 pacific 8 pacific 9 cohort 9 cohort 10 studies 10 studies 11 collaboration 12 were 14 used 13 thus 14 used 14 used 15 to 15 to 16 investigate 16 investigate 18 risk 16 investigate 22 in 17 the 18 risk 18 risk 19 factors 18 risk 21 stroke 19 factors 21 stroke 22 in 24 region 23 the 24 region raised systolic blood pressure and diabetes were found to be key risk factors for both ischemic ( [is] [ )(and hemorrhagic ( hs ) stroke . 0 ###LEFT-WALL### 5 and 0 ###LEFT-WALL### 26 . 1 raised 4 pressure 1 raised 5 and 2 systolic 3 blood 3 blood 4 pressure 5 and 11 key 6 diabetes 7 were 7 were 8 found 8 found 9 to 9 to 10 be 10 be 11 key 11 key 13 factors 12 risk 13 factors 13 factors 14 for 14 for 20 )(and 15 both 20 )(and 16 ischemic 20 )(and 17 ( 20 )(and 20 )(and 25 stroke 21 hemorrhagic 23 hs 21 hemorrhagic 24 ) 21 hemorrhagic 25 stroke 22 ( 23 hs 23 hs 24 ) after adjustment for other risk factors , every extra 10 mmhg systolic blood pressure increased risk of is by 36 % and hs by 69 % , whilst diabetes increased risk of is by 170 % and hs by 147 % . 0 ###LEFT-WALL### 14 pressure 0 ###LEFT-WALL### 15 increased 0 ###LEFT-WALL### 42 . 1 after 2 adjustment 1 after 7 , 1 after 14 pressure 2 adjustment 3 for 3 for 6 factors 4 other 6 factors 5 risk 6 factors 8 every 14 pressure 9 extra 14 pressure 10 10 11 mmhg 11 mmhg 14 pressure 12 systolic 13 blood 13 blood 14 pressure 14 pressure 15 increased 15 increased 16 risk 15 increased 28 whilst 16 risk 17 of 17 of 22 and 18 is 19 by 18 is 22 and 19 by 21 % 20 36 21 % 22 and 23 hs 22 and 27 , 23 hs 24 by 24 by 26 % 25 69 26 % 28 whilst 29 diabetes 28 whilst 30 increased 29 diabetes 30 increased 30 increased 31 risk 30 increased 39 by 31 risk 32 of 32 of 37 and 33 is 34 by 33 is 37 and 34 by 36 % 35 170 36 % 37 and 38 hs 39 by 41 % 40 147 41 % smoking was also an important risk factor for is and hs ; risk was reduced by quitting . 0 ###LEFT-WALL### 1 smoking 0 ###LEFT-WALL### 2 was 0 ###LEFT-WALL### 12 ; 0 ###LEFT-WALL### 18 . 1 smoking 2 was 2 was 3 also 2 was 7 factor 4 an 5 important 4 an 7 factor 5 important 7 factor 6 risk 7 factor 7 factor 8 for 8 for 11 hs 9 is 10 and 10 and 11 hs 12 ; 13 risk 12 ; 15 reduced 13 risk 14 was 14 was 15 reduced 15 reduced 16 by 16 by 17 quitting in the context of increasing extinction rates and the potential loss of essential evolutionary biological and anthropological information , it is an important task to support efforts to prepare , preserve , and curate collections of histological brain sections ; to disseminate information on such collections in the neuroscience community [;] and to make the collections publicly available . 0 ###LEFT-WALL### 20 it 0 ###LEFT-WALL### 40 ; 0 ###LEFT-WALL### 59 . 1 in 8 and 1 in 20 it 2 the 3 context 3 context 4 of 3 context 8 and 4 of 7 rates 5 increasing 6 extinction 6 extinction 7 rates 8 and 11 loss 8 and 19 , 9 the 11 loss 10 potential 11 loss 11 loss 12 of 12 of 18 information 13 essential 18 information 14 evolutionary 18 information 15 biological 16 and 16 and 17 anthropological 16 and 18 information 20 it 21 is 21 is 33 and 22 an 24 task 23 important 24 task 24 task 25 to 24 task 30 , 25 to 27 efforts 26 support 27 efforts 27 efforts 28 to 27 efforts 29 prepare 28 to 29 prepare 30 , 31 preserve 30 , 33 and 32 , 33 and 33 and 35 collections 33 and 40 ; 34 curate 35 collections 35 collections 36 of 36 of 39 sections 37 histological 38 brain 38 brain 39 sections 40 ; 41 to 40 ; 52 and 41 to 52 and 42 disseminate 43 information 42 disseminate 47 in 42 disseminate 52 and 43 information 44 on 44 on 46 collections 45 such 46 collections 47 in 50 community 48 the 50 community 49 neuroscience 50 community 52 and 53 to 52 and 54 make 53 to 54 make 54 make 56 collections 54 make 58 available 55 the 56 collections 57 publicly 58 available this review emphasizes the importance of complete , serially sectioned human brains of different ontogenetic stages as well as those of adult [and] old human individuals for neurobiological and medical research . 0 ###LEFT-WALL### 2 review 0 ###LEFT-WALL### 3 emphasizes 0 ###LEFT-WALL### 32 . 1 this 2 review 2 review 3 emphasizes 3 emphasizes 5 importance 3 emphasizes 19 as 4 the 5 importance 5 importance 6 of 6 of 12 brains 7 complete 8 , 7 complete 12 brains 9 serially 10 sectioned 10 sectioned 12 brains 11 human 12 brains 12 brains 13 of 13 of 16 stages 14 different 16 stages 15 ontogenetic 16 stages 17 as 18 well 18 well 19 as 19 as 20 those 20 those 21 of 21 of 26 individuals 22 adult 26 individuals 24 old 26 individuals 25 human 26 individuals 26 individuals 27 for 27 for 31 research 28 neurobiological 29 and 29 and 30 medical 29 and 31 research such histological sections enable microstructural analyses and anatomical evaluations of functional and structural neuroimaging data , for example , based on magnetic resonance imaging . 0 ###LEFT-WALL### 3 sections 0 ###LEFT-WALL### 20 based 0 ###LEFT-WALL### 25 . 1 such 3 sections 2 histological 3 sections 3 sections 4 enable 4 enable 7 and 5 microstructural 6 analyses 6 analyses 7 and 7 and 9 evaluations 7 and 10 of 8 anatomical 9 evaluations 10 of 14 neuroimaging 11 functional 12 and 12 and 13 structural 12 and 14 neuroimaging 14 neuroimaging 15 data 14 neuroimaging 20 based 15 data 20 based 16 , 18 example 17 for 18 example 18 example 19 , 18 example 20 based 20 based 21 on 21 on 24 imaging 22 magnetic 23 resonance 23 resonance 24 imaging here , this review provides the first detailed and updated account of the content of the stephan , zilles , and zilles - amunts collections [,] [which] consist of serially sectioned and cell body - and myelin - stained histological preparations . 0 ###LEFT-WALL### 4 review 0 ###LEFT-WALL### 18 , 0 ###LEFT-WALL### 42 . 1 here 2 , 1 here 4 review 3 this 4 review 4 review 5 provides 5 provides 9 and 6 the 7 first 6 the 8 detailed 8 detailed 9 and 9 and 11 account 9 and 12 of 9 and 15 of 10 updated 11 account 12 of 14 content 13 the 14 content 15 of 17 stephan 16 the 17 stephan 18 , 36 and 18 , 38 - 19 zilles 21 and 20 , 21 and 21 and 22 zilles 21 and 23 - 21 and 24 amunts 21 and 31 sectioned 21 and 32 and 24 amunts 25 collections 24 amunts 29 of 24 amunts 31 sectioned 25 collections 28 consist 28 consist 29 of 30 serially 31 sectioned 32 and 34 body 32 and 36 and 33 cell 34 body 35 - 36 and 36 and 37 myelin 38 - 41 preparations 39 stained 41 preparations 40 histological 41 preparations finally , this review will give an overview [of] past and recent research using these collections to increase our understanding of the detailed patterns of divergent brain evolution in primates as well as of the structural organization of the human brain . 0 ###LEFT-WALL### 4 review 0 ###LEFT-WALL### 18 increase 0 ###LEFT-WALL### 42 . 1 finally 2 , 1 finally 4 review 3 this 4 review 4 review 5 will 5 will 6 give 6 give 10 past 6 give 11 and 6 give 14 using 7 an 10 past 8 overview 10 past 11 and 13 research 12 recent 13 research 14 using 16 collections 14 using 17 to 15 these 16 collections 17 to 18 increase 18 increase 20 understanding 18 increase 29 in 18 increase 31 as 19 our 20 understanding 20 understanding 21 of 20 understanding 25 of 21 of 24 patterns 22 the 24 patterns 23 detailed 24 patterns 25 of 28 evolution 26 divergent 27 brain 27 brain 28 evolution 29 in 30 primates 31 as 32 well 32 well 33 as 32 well 38 of 33 as 34 of 34 of 37 organization 35 the 37 organization 36 structural 37 organization 38 of 41 brain 39 the 41 brain 40 human 41 brain the university of geneva brain collection was founded at the beginning of the 20th century . 0 ###LEFT-WALL### 6 collection 0 ###LEFT-WALL### 8 founded 0 ###LEFT-WALL### 16 . 1 the 6 collection 2 university 3 of 2 university 6 collection 3 of 4 geneva 5 brain 6 collection 6 collection 7 was 7 was 8 founded 8 founded 9 at 9 at 11 beginning 10 the 11 beginning 11 beginning 12 of 12 of 15 century 13 the 15 century 14 20th 15 century today , it consists of 10,154 formaldehyde - or buffered formaldehyde - fixed brains obtained from the autopsies of the department of psychiatry [and] , since 1971 , from the department of geriatrics . 0 ###LEFT-WALL### 3 it 0 ###LEFT-WALL### 9 or 0 ###LEFT-WALL### 34 . 1 today 2 , 1 today 3 it 3 it 9 or 4 consists 5 of 4 consists 9 or 5 of 7 formaldehyde 6 10,154 7 formaldehyde 8 - 9 or 9 or 10 buffered 9 or 26 since 9 or 29 from 10 buffered 11 formaldehyde 11 formaldehyde 14 brains 12 - 14 brains 13 fixed 14 brains 14 brains 15 obtained 14 brains 16 from 14 brains 25 , 16 from 18 autopsies 17 the 18 autopsies 18 autopsies 19 of 18 autopsies 22 of 19 of 21 department 20 the 21 department 22 of 23 psychiatry 25 , 26 since 26 since 27 1971 26 since 28 , 29 from 31 department 30 the 31 department 31 department 32 of 32 of 33 geriatrics more than 100,000 paraffin - embedded blocks and 200,000 histological slides have also been collected since 1901 . 0 ###LEFT-WALL### 4 paraffin 0 ###LEFT-WALL### 5 - 1 more 2 than 2 than 3 100,000 3 100,000 4 paraffin 5 - 8 and 5 - 14 been 5 - 18 . 6 embedded 7 blocks 7 blocks 8 and 8 and 11 slides 8 and 12 have 9 200,000 11 slides 10 histological 11 slides 12 have 14 been 13 also 14 been 14 been 15 collected 15 collected 16 since 16 since 17 1901 from the time of its creation , this collection has served as an important resource for pathological studies and clinicopathological correlations , primarily in the field of dementing illnesses and brain aging research . 0 ###LEFT-WALL### 9 collection 0 ###LEFT-WALL### 11 served 0 ###LEFT-WALL### 34 . 1 from 3 time 1 from 7 , 1 from 9 collection 2 the 3 time 3 time 4 of 4 of 6 creation 5 its 6 creation 8 this 9 collection 9 collection 10 has 10 has 11 served 11 served 12 as 11 served 23 primarily 12 as 15 resource 13 an 15 resource 14 important 15 resource 15 resource 16 for 16 for 19 and 17 pathological 18 studies 18 studies 19 and 19 and 21 correlations 19 and 22 , 20 clinicopathological 21 correlations 23 primarily 24 in 24 in 30 and 25 the 26 field 26 field 27 of 26 field 30 and 27 of 29 illnesses 28 dementing 29 illnesses 30 and 31 brain 30 and 32 aging 32 aging 33 research these materials have permitted a number of original neuropathological observations , such as the classification of pick 's disease by constantinidis , or the description of dyshoric angiopathy and laminar sclerosis by morel . 0 ###LEFT-WALL### 2 materials 0 ###LEFT-WALL### 4 permitted 0 ###LEFT-WALL### 34 . 1 these 2 materials 2 materials 3 have 3 have 4 permitted 4 permitted 23 or 4 permitted 32 by 5 a 6 number 6 number 7 of 6 number 23 or 7 of 10 observations 8 original 10 observations 9 neuropathological 10 observations 10 observations 13 as 11 , 13 as 12 such 13 as 13 as 15 classification 13 as 22 , 14 the 15 classification 15 classification 16 of 16 of 19 disease 17 pick 18 's 18 's 19 disease 19 disease 20 by 20 by 21 constantinidis 22 , 23 or 23 or 25 description 23 or 26 of 24 the 25 description 26 of 29 and 27 dyshoric 28 angiopathy 28 angiopathy 29 and 29 and 31 sclerosis 30 laminar 31 sclerosis 32 by 33 morel the large number of cases , including some very rare conditions , provides a unique resource and an opportunity for worldwide collaborations . 0 ###LEFT-WALL### 3 number 0 ###LEFT-WALL### 13 provides 0 ###LEFT-WALL### 23 . 1 the 3 number 2 large 3 number 3 number 4 of 3 number 13 provides 4 of 5 cases 5 cases 7 including 6 , 7 including 7 including 11 conditions 7 including 12 , 8 some 11 conditions 9 very 10 rare 10 rare 11 conditions 13 provides 17 and 14 a 16 resource 15 unique 16 resource 16 resource 17 and 17 and 19 opportunity 17 and 20 for 18 an 19 opportunity 20 for 22 collaborations 21 worldwide 22 collaborations areal bone mineral density ( abmd ) measured by dual - energy x - ray absorptiometry ( dxa ) identifies 20 % of men who will sustain fragility fractures . 0 ###LEFT-WALL### 1 areal 0 ###LEFT-WALL### 20 identifies 0 ###LEFT-WALL### 30 . 1 areal 4 density 1 areal 8 measured 1 areal 16 absorptiometry 1 areal 20 identifies 2 bone 4 density 3 mineral 4 density 4 density 6 abmd 4 density 8 measured 5 ( 6 abmd 6 abmd 7 ) 8 measured 9 by 9 by 12 energy 10 dual 11 - 10 dual 12 energy 12 energy 13 x 14 - 16 absorptiometry 15 ray 16 absorptiometry 16 absorptiometry 18 dxa 16 absorptiometry 19 ) 17 ( 18 dxa 18 dxa 19 ) 20 identifies 22 % 21 20 22 % 22 % 23 of 23 of 24 men 24 men 25 who 24 men 26 will 25 who 26 will 26 will 27 sustain 27 sustain 29 fractures 28 fragility 29 fractures thus we need better fracture predictors in men . 0 ###LEFT-WALL### 2 we 0 ###LEFT-WALL### 3 need 0 ###LEFT-WALL### 9 . 1 thus 2 we 2 we 3 need 3 need 6 predictors 3 need 7 in 4 better 5 fracture 5 fracture 6 predictors 7 in 8 men we assessed the association between the low - trauma prevalent fractures and bone microarchitecture assessed at the distal radius and tibia by high - resolution peripheral quantitative computed tomography ( hr - pqct ) in 920 men aged 50 years [of] older . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 assessed 0 ###LEFT-WALL### 32 - 0 ###LEFT-WALL### 43 . 1 we 2 assessed 2 assessed 4 association 2 assessed 5 between 3 the 4 association 5 between 20 and 6 the 14 microarchitecture 7 low 8 - 7 low 9 trauma 9 trauma 14 microarchitecture 10 prevalent 11 fractures 11 fractures 12 and 12 and 13 bone 12 and 14 microarchitecture 14 microarchitecture 15 assessed 14 microarchitecture 16 at 14 microarchitecture 20 and 16 at 19 radius 17 the 19 radius 18 distal 19 radius 20 and 21 tibia 20 and 22 by 22 by 29 tomography 23 high 24 - 23 high 25 resolution 25 resolution 29 tomography 26 peripheral 29 tomography 27 quantitative 29 tomography 28 computed 29 tomography 29 tomography 31 hr 30 ( 31 hr 31 hr 32 - 32 - 37 men 32 - 38 aged 33 pqct 34 ) 33 pqct 37 men 35 in 36 920 35 in 37 men 37 men 38 aged 38 aged 42 older 39 50 40 years 40 years 42 older ninety - eight men had vertebral fractures identified on the vertebral fracture assessment software of the hologic discovery a device using the semiquantitative criteria , whereas 100 men reported low - trauma peripheral fractures . 0 ###LEFT-WALL### 4 men 0 ###LEFT-WALL### 5 had 0 ###LEFT-WALL### 31 - 0 ###LEFT-WALL### 35 . 1 ninety 2 - 2 - 3 eight 2 - 4 men 4 men 5 had 5 had 7 fractures 6 vertebral 7 fractures 7 fractures 8 identified 7 fractures 9 on 9 on 14 software 10 the 14 software 11 vertebral 12 fracture 12 fracture 13 assessment 13 assessment 14 software 14 software 15 of 15 of 20 device 16 the 20 device 17 hologic 18 discovery 18 discovery 19 a 18 discovery 20 device 20 device 21 using 21 using 24 criteria 21 using 26 whereas 22 the 24 criteria 23 semiquantitative 24 criteria 25 , 26 whereas 26 whereas 28 men 26 whereas 29 reported 26 whereas 31 - 27 100 28 men 28 men 29 reported 29 reported 30 low 31 - 34 fractures 32 trauma 34 fractures 33 peripheral 34 fractures men with vertebral fractures had poor bone microarchitecture . 0 ###LEFT-WALL### 1 men 0 ###LEFT-WALL### 5 had 0 ###LEFT-WALL### 9 . 1 men 2 with 1 men 5 had 2 with 4 fractures 3 vertebral 4 fractures 5 had 8 microarchitecture 6 poor 7 bone 7 bone 8 microarchitecture however , in the men with vertebral fractures , only cortical volumetric density ( d.cort ) and cortical thickness ( c.th ) remained significantly lower at both the radius and tibia after adjustment for abmd of ultradistal radius and hip , respectively . 0 ###LEFT-WALL### 19 thickness 0 ###LEFT-WALL### 23 remained 1 however 2 , 1 however 19 thickness 3 in 17 and 3 in 19 thickness 4 the 5 men 5 men 6 with 5 men 17 and 6 with 8 fractures 7 vertebral 8 fractures 8 fractures 13 density 9 , 10 only 9 , 13 density 11 cortical 13 density 12 volumetric 13 density 13 density 15 d.cort 13 density 16 ) 14 ( 15 d.cort 15 d.cort 16 ) 17 and 18 cortical 19 thickness 21 c.th 19 thickness 23 remained 20 ( 21 c.th 21 c.th 22 ) 23 remained 25 lower 23 remained 26 at 23 remained 32 after 23 remained 34 for 23 remained 42 respectively 24 significantly 25 lower 26 at 30 and 27 both 30 and 28 the 29 radius 29 radius 30 and 30 and 31 tibia 32 after 33 adjustment 34 for 39 and 35 abmd 36 of 35 abmd 39 and 36 of 38 radius 37 ultradistal 38 radius 39 and 40 hip 41 , 42 respectively 42 respectively 43 . low d.cort and c.th were associated with higher prevalence of vertebral fractures regardless of abmd . 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 6 associated 0 ###LEFT-WALL### 16 . 1 low 3 and 2 d.cort 3 and 3 and 4 c.th 3 and 5 were 5 were 6 associated 6 associated 7 with 6 associated 14 of 7 with 9 prevalence 8 higher 9 prevalence 9 prevalence 10 of 10 of 12 fractures 11 vertebral 12 fractures 13 regardless 14 of 14 of 15 abmd severe vertebral fractures also were associated with poor trabecular microarchitecture regardless of abmd . 0 ###LEFT-WALL### 3 fractures 0 ###LEFT-WALL### 6 associated 0 ###LEFT-WALL### 14 . 1 severe 3 fractures 2 vertebral 3 fractures 3 fractures 5 were 4 also 5 were 5 were 6 associated 6 associated 7 with 6 associated 12 of 7 with 10 microarchitecture 8 poor 10 microarchitecture 9 trabecular 10 microarchitecture 11 regardless 12 of 12 of 13 abmd men with peripheral fractures had poor bone microarchitecture . 0 ###LEFT-WALL### 1 men 0 ###LEFT-WALL### 5 had 0 ###LEFT-WALL### 9 . 1 men 2 with 1 men 5 had 2 with 4 fractures 3 peripheral 4 fractures 5 had 8 microarchitecture 6 poor 7 bone 7 bone 8 microarchitecture however , after adjustment for abmd , all microarchitectural parameters became nonsignificant . 0 ###LEFT-WALL### 10 parameters 0 ###LEFT-WALL### 11 became 0 ###LEFT-WALL### 13 . 1 however 2 , 1 however 10 parameters 2 , 3 after 3 after 4 adjustment 3 after 7 , 3 after 10 parameters 4 adjustment 5 for 5 for 6 abmd 8 all 10 parameters 9 microarchitectural 10 parameters 10 parameters 11 became 11 became 12 nonsignificant in 15 men with multiple peripheral fractures , trabecular spacing and distribution remained increased after adjustment for abmd . 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 13 remained 0 ###LEFT-WALL### 19 . 1 in 3 men 1 in 8 , 1 in 11 and 2 15 3 men 3 men 4 with 4 with 7 fractures 5 multiple 7 fractures 6 peripheral 7 fractures 9 trabecular 10 spacing 9 trabecular 11 and 11 and 12 distribution 11 and 13 remained 13 remained 14 increased 14 increased 15 after 14 increased 17 for 15 after 16 adjustment 17 for 18 abmd thus , in men , vertebral fractures and their severity [are] associated [with] impaired cortical bone , even after adjustment for abmd . 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 17 , 0 ###LEFT-WALL### 23 . 1 thus 2 , 1 thus 8 and 2 , 3 in 3 in 4 men 3 in 5 , 3 in 8 and 6 vertebral 7 fractures 7 fractures 8 and 8 and 10 severity 8 and 12 associated 8 and 14 impaired 8 and 17 , 9 their 10 severity 14 impaired 15 cortical 16 bone 17 , 17 , 18 even 18 even 19 after 19 after 20 adjustment 20 adjustment 21 for 21 for 22 abmd the association between peripheral fractures and bone microarchitecture was weaker [and] nonsignificant after adjustment for abmd . 0 ###LEFT-WALL### 2 association 0 ###LEFT-WALL### 9 was 0 ###LEFT-WALL### 17 . 1 the 2 association 2 association 3 between 2 association 9 was 3 between 6 and 4 peripheral 5 fractures 5 fractures 6 and 6 and 8 microarchitecture 7 bone 8 microarchitecture 9 was 12 nonsignificant 10 weaker 12 nonsignificant 12 nonsignificant 13 after 13 after 14 adjustment 14 adjustment 15 for 15 for 16 abmd thus bone microarchitecture may be a determinant of bone fragility in men , which should be investigated in prospective studies . 0 ###LEFT-WALL### 3 microarchitecture 0 ###LEFT-WALL### 5 be 0 ###LEFT-WALL### 13 , 0 ###LEFT-WALL### 21 . 1 thus 3 microarchitecture 2 bone 3 microarchitecture 3 microarchitecture 4 may 4 may 5 be 5 be 7 determinant 6 a 7 determinant 7 determinant 8 of 8 of 10 fragility 9 bone 10 fragility 10 fragility 11 in 11 in 12 men 13 , 14 which 13 , 17 investigated 14 which 15 should 15 should 16 be 16 be 17 investigated 17 investigated 18 in 18 in 20 studies 19 prospective 20 studies measurement of bone mass [,] geometry , density , and strength are critical in bone research and clinical studies . 0 ###LEFT-WALL### 1 measurement 0 ###LEFT-WALL### 12 are 0 ###LEFT-WALL### 20 . 1 measurement 2 of 1 measurement 12 are 2 of 10 and 3 bone 6 geometry 4 mass 6 geometry 6 geometry 7 , 7 , 8 density 7 , 10 and 9 , 10 and 10 and 11 strength 12 are 19 studies 13 critical 14 in 13 critical 17 and 14 in 16 research 15 bone 16 research 17 and 18 clinical 17 and 19 studies for peripheral quantitative computed tomography ( pqct ) , single and repeated measurements are particularly adversely affected by movement and positional variation . 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 17 affected 0 ###LEFT-WALL### 23 . 1 for 5 tomography 1 for 9 , 1 for 11 and 2 peripheral 5 tomography 3 quantitative 5 tomography 4 computed 5 tomography 5 tomography 7 pqct 6 ( 7 pqct 7 pqct 8 ) 10 single 11 and 11 and 13 measurements 11 and 14 are 12 repeated 13 measurements 14 are 15 particularly 14 are 17 affected 15 particularly 16 adversely 17 affected 18 by 18 by 20 and 19 movement 20 and 20 and 22 variation 21 positional 22 variation dual - energy x - ray absorptiometry ( dxa ) - derived indices may alleviate these problems and provide useful alternative assessments . 0 ###LEFT-WALL### 13 indices 0 ###LEFT-WALL### 18 and 0 ###LEFT-WALL### 23 . 1 dual 3 energy 1 dual 11 - 1 dual 13 indices 2 - 3 energy 3 energy 4 x 3 energy 7 absorptiometry 3 energy 11 - 5 - 7 absorptiometry 6 ray 7 absorptiometry 7 absorptiometry 9 dxa 7 absorptiometry 11 - 8 ( 9 dxa 9 dxa 10 ) 12 derived 13 indices 13 indices 14 may 14 may 18 and 15 alleviate 17 problems 15 alleviate 18 and 16 these 17 problems 18 and 19 provide 18 and 22 assessments 20 useful 22 assessments 21 alternative 22 assessments to evaluate this hypothesis , distal radius dxa and pqct indices were compared in 101 healthy females aged 8.0 to 22.8 years ( prepuberty to adulthood ) , reflecting a broad range of body sizes , physical maturity , and activity exposures . 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 13 compared 0 ###LEFT-WALL### 36 , 0 ###LEFT-WALL### 43 . 1 to 2 evaluate 1 to 5 , 1 to 9 and 2 evaluate 4 hypothesis 3 this 4 hypothesis 6 distal 8 dxa 7 radius 8 dxa 8 dxa 9 and 9 and 10 pqct 9 and 11 indices 9 and 12 were 9 and 13 compared 11 indices 12 were 13 compared 14 in 13 compared 20 to 14 in 17 females 15 101 17 females 16 healthy 17 females 17 females 18 aged 18 aged 19 8.0 20 to 22 years 21 22.8 22 years 22 years 24 prepuberty 22 years 29 reflecting 23 ( 24 prepuberty 24 prepuberty 25 to 24 prepuberty 27 ) 25 to 26 adulthood 28 , 29 reflecting 29 reflecting 32 range 29 reflecting 36 , 30 a 31 broad 30 a 32 range 31 broad 32 range 32 range 33 of 33 of 35 sizes 34 body 35 sizes 36 , 40 and 37 physical 38 maturity 38 maturity 40 and 39 , 40 and 40 and 42 exposures 41 activity 42 exposures at the diaphysis , correlations were ρ [=] +0.74 to +0.98 , with strong intermethod agreement for most indices . 0 ###LEFT-WALL### 5 correlations 0 ###LEFT-WALL### 6 were 1 at 3 diaphysis 1 at 4 , 1 at 5 correlations 2 the 3 diaphysis 5 correlations 6 were 6 were 9 +0.74 7 ρ 9 +0.74 9 +0.74 10 to 9 +0.74 13 with 10 to 11 +0.98 12 , 13 with 13 with 16 agreement 13 with 20 . 14 strong 15 intermethod 15 intermethod 16 agreement 16 agreement 17 for 17 for 19 indices 18 most 19 indices at the metaphysis [,] correlations were ρ = +0.64 to +0.97 ; intermethod agreement improved with modifications to the simplified geometric formulas more closely reflecting metaphyseal bone geometry . 0 ###LEFT-WALL### 1 at 0 ###LEFT-WALL### 8 = 0 ###LEFT-WALL### 12 ; 0 ###LEFT-WALL### 29 . 1 at 3 metaphysis 1 at 8 = 2 the 3 metaphysis 3 metaphysis 5 correlations 3 metaphysis 6 were 5 correlations 6 were 7 ρ 8 = 8 = 9 +0.64 9 +0.64 10 to 10 to 11 +0.97 12 ; 14 agreement 12 ; 15 improved 13 intermethod 14 agreement 14 agreement 15 improved 15 improved 16 with 16 with 17 modifications 17 modifications 18 to 18 to 22 formulas 19 the 22 formulas 20 simplified 22 formulas 21 geometric 22 formulas 22 formulas 25 reflecting 23 more 24 closely 24 closely 25 reflecting 25 reflecting 28 geometry 26 metaphyseal 27 bone 27 bone 28 geometry further improvements may be possible because skeletal size and maturity - related biases in agreement were detected . 0 ###LEFT-WALL### 2 improvements 0 ###LEFT-WALL### 4 be 0 ###LEFT-WALL### 18 . 1 further 2 improvements 2 improvements 3 may 3 may 4 be 4 be 5 possible 5 possible 6 because 6 because 9 and 6 because 17 detected 7 skeletal 8 size 8 size 9 and 9 and 10 maturity 9 and 16 were 11 - 12 related 12 related 13 biases 12 related 14 in 12 related 16 were 14 in 15 agreement 16 were 17 detected overall , dxa - derived indices may provide a useful assessment of bone geometry , density , and theoretical strength contingent on appropriate consideration of their limitations . 0 ###LEFT-WALL### 6 indices 0 ###LEFT-WALL### 8 provide 0 ###LEFT-WALL### 15 , 0 ###LEFT-WALL### 28 . 1 overall 3 dxa 2 , 3 dxa 3 dxa 4 - 3 dxa 5 derived 5 derived 6 indices 6 indices 7 may 7 may 8 provide 8 provide 11 assessment 9 a 11 assessment 10 useful 11 assessment 11 assessment 12 of 12 of 14 geometry 13 bone 14 geometry 15 , 18 and 16 density 18 and 17 , 18 and 18 and 20 strength 18 and 21 contingent 19 theoretical 20 strength 21 contingent 22 on 22 on 24 consideration 23 appropriate 24 consideration 24 consideration 25 of 25 of 27 limitations 26 their 27 limitations although aging is inexorable , aging well is not . 0 ###LEFT-WALL### 6 aging 0 ###LEFT-WALL### 8 is 0 ###LEFT-WALL### 10 . 1 although 2 aging 1 although 3 is 1 although 5 , 1 although 6 aging 2 aging 3 is 3 is 4 inexorable 6 aging 7 well 6 aging 8 is 8 is 9 not [from] the perspective of research in rats and complementary models , reproductive experience has significant effects [;] indeed , benefits , which include better - than - average cognitive skills , a slowing of the slope of decline , and a healthier brain [and/or] nervous system well later into life . 0 ###LEFT-WALL### 10 models 0 ###LEFT-WALL### 11 , 2 the 3 perspective 3 perspective 4 of 3 perspective 6 in 3 perspective 8 and 4 of 5 research 6 in 7 rats 8 and 9 complementary 8 and 10 models 11 , 13 experience 11 , 19 , 11 , 21 , 12 reproductive 13 experience 13 experience 19 , 14 has 16 effects 14 has 18 indeed 14 has 19 , 15 significant 16 effects 19 , 20 benefits 21 , 22 which 21 , 23 include 22 which 23 include 23 include 24 better 23 include 26 than 23 include 30 skills 25 - 26 than 26 than 27 - 28 average 30 skills 29 cognitive 30 skills 30 skills 40 and 31 , 40 and 32 a 33 slowing 33 slowing 34 of 33 slowing 40 and 34 of 36 slope 35 the 36 slope 36 slope 37 of 37 of 38 decline 39 , 40 and 40 and 47 well 40 and 49 into 40 and 51 . 41 a 47 well 42 healthier 43 brain 43 brain 47 well 45 nervous 46 system 46 system 47 well 47 well 48 later 49 into 50 life work from our lab and others has suggested that the events of pregnancy and parturition , collectively referred to as reproductive experience - an amalgam of hormone exposure , sensory stimulation , and offspring behavioral experience and interaction - may summate to flatten the degree of decline normally associated [with] aging . 0 ###LEFT-WALL### 1 work 0 ###LEFT-WALL### 19 to 0 ###LEFT-WALL### 23 - 1 work 2 from 1 work 7 has 2 from 5 and 3 our 4 lab 4 lab 5 and 5 and 6 others 7 has 8 suggested 8 suggested 9 that 9 that 14 and 9 that 19 to 10 the 11 events 11 events 12 of 11 events 14 and 12 of 13 pregnancy 14 and 15 parturition 14 and 16 , 14 and 19 to 17 collectively 19 to 18 referred 19 to 19 to 22 experience 20 as 21 reproductive 21 reproductive 22 experience 23 - 25 amalgam 24 an 25 amalgam 25 amalgam 26 of 26 of 28 exposure 27 hormone 28 exposure 28 exposure 33 and 29 , 33 and 30 sensory 31 stimulation 31 stimulation 33 and 32 , 33 and 33 and 34 offspring 33 and 37 and 33 and 41 summate 33 and 46 of 33 and 52 . 35 behavioral 36 experience 36 experience 37 and 37 and 38 interaction 37 and 39 - 37 and 40 may 40 may 41 summate 41 summate 42 to 42 to 43 flatten 43 flatten 45 degree 44 the 45 degree 46 of 51 aging 47 decline 51 aging 48 normally 49 associated 49 associated 51 aging mimicking the effects [of] [an] enriched environment , reproductive experience has been shown [to] : enhance/protect cognition and decrease anxiety well out to two - plus years ; result in fewer hippocampal deposits of the alzheimer 's disease herald , amyloid precursor protein ( app ) [;] [and] , in general , lead to [a] healthier biology . 0 ###LEFT-WALL### 1 mimicking 0 ###LEFT-WALL### 6 enriched 0 ###LEFT-WALL### 8 , 1 mimicking 3 effects 1 mimicking 6 enriched 2 the 3 effects 6 enriched 7 environment 8 , 10 experience 8 , 13 shown 8 , 15 : 9 reproductive 10 experience 10 experience 11 has 11 has 12 been 12 been 13 shown 15 : 18 and 15 : 25 - 16 enhance/protect 17 cognition 17 cognition 18 and 18 and 21 well 18 and 25 - 19 decrease 20 anxiety 20 anxiety 21 well 21 well 22 out 22 out 23 to 23 to 24 two 25 - 27 years 25 - 28 ; 26 plus 27 years 28 ; 29 result 28 ; 40 , 29 result 30 in 30 in 33 deposits 31 fewer 33 deposits 32 hippocampal 33 deposits 33 deposits 34 of 34 of 39 herald 35 the 36 alzheimer 36 alzheimer 37 's 37 's 39 herald 38 disease 39 herald 40 , 41 amyloid 41 amyloid 43 protein 42 precursor 43 protein 43 protein 45 app 43 protein 50 in 44 ( 45 app 45 app 46 ) 49 , 50 in 50 in 53 lead 50 in 58 . 51 general 52 , 51 general 53 lead 53 lead 54 to 54 to 57 biology 56 healthier 57 biology based on a suite of recent work in organisms as diverse as nematodes , flies , and mammals , the ubiquitous hormone insulin and its large family of related substances and receptors may play a major role in mediating some of the effects of re on the parameters of aging studied thus far . 0 ###LEFT-WALL### 24 and 0 ###LEFT-WALL### 34 play 0 ###LEFT-WALL### 54 . 1 based 2 on 1 based 14 , 1 based 24 and 2 on 4 suite 3 a 4 suite 4 suite 5 of 5 of 7 work 6 recent 7 work 7 work 8 in 8 in 9 organisms 9 organisms 11 diverse 10 as 11 diverse 11 diverse 12 as 12 as 13 nematodes 15 flies 17 and 16 , 17 and 17 and 18 mammals 17 and 19 , 19 , 23 insulin 19 , 24 and 20 the 23 insulin 21 ubiquitous 22 hormone 22 hormone 23 insulin 24 and 27 family 24 and 28 of 24 and 33 may 25 its 27 family 26 large 27 family 28 of 31 and 29 related 30 substances 30 substances 31 and 31 and 32 receptors 33 may 34 play 34 play 37 role 34 play 38 in 35 a 36 major 35 a 37 role 36 major 37 role 38 in 39 mediating 39 mediating 40 some 40 some 41 of 40 some 46 on 40 some 49 of 41 of 43 effects 42 the 43 effects 43 effects 44 of 44 of 45 re 46 on 48 parameters 47 the 48 parameters 49 of 50 aging 50 aging 51 studied 50 aging 53 far 52 thus 53 far we will discuss the current set of data that suggest mechanisms for successful biological and neurobiological aging , and the implications for understanding aging and senescence in their broadest terms . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 discuss 0 ###LEFT-WALL### 31 . 1 we 2 will 2 will 3 discuss 3 discuss 6 set 3 discuss 12 for 3 discuss 22 for 3 discuss 27 in 4 the 6 set 5 current 6 set 6 set 7 of 7 of 8 data 8 data 9 that 8 data 10 suggest 9 that 10 suggest 10 suggest 11 mechanisms 12 for 19 and 13 successful 17 aging 14 biological 15 and 15 and 16 neurobiological 15 and 17 aging 17 aging 19 and 18 , 19 and 19 and 21 implications 20 the 21 implications 22 for 25 and 23 understanding 24 aging 23 understanding 25 and 25 and 26 senescence 27 in 30 terms 28 their 29 broadest 28 their 30 terms unlabelled : we observed similar prevalence of short vertebral height without endplate depression ( svh ) in young women aged 20 - 39 years and older women aged 55 - 79 years . 0 ###LEFT-WALL### 1 unlabelled 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 33 . 1 unlabelled 2 : 2 : 25 and 3 we 4 observed 4 observed 6 prevalence 5 similar 6 prevalence 6 prevalence 7 of 6 prevalence 17 in 6 prevalence 20 aged 7 of 10 height 8 short 10 height 9 vertebral 10 height 10 height 11 without 10 height 15 svh 11 without 13 depression 12 endplate 13 depression 14 ( 15 svh 15 svh 16 ) 17 in 19 women 18 young 19 women 20 aged 22 - 21 20 22 - 22 - 23 39 23 39 24 years 24 years 25 and 25 and 32 years 26 older 27 women 27 women 28 aged 28 aged 30 - 29 55 30 - 30 - 31 79 31 79 32 years there was no association between svh and low bone density . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 was 0 ###LEFT-WALL### 11 . 1 there 2 was 2 was 4 association 3 no 4 association 4 association 5 between 5 between 7 and 6 svh 7 and 7 and 10 density 8 low 9 bone 9 bone 10 density in older women , therefore , svh may be largely long standing and not indicative [of] osteoporotic fracture . 0 ###LEFT-WALL### 7 svh 0 ###LEFT-WALL### 9 be 0 ###LEFT-WALL### 19 . 1 in 3 women 1 in 4 , 1 in 7 svh 2 older 3 women 4 , 5 therefore 5 therefore 6 , 5 therefore 7 svh 7 svh 8 may 8 may 9 be 9 be 13 and 10 largely 11 long 11 long 12 standing 12 standing 13 and 13 and 14 not 13 and 18 fracture 15 indicative 18 fracture 17 osteoporotic 18 fracture introduction : algorithm - based qualitative ( abq ) definition of osteoporotic vertebral fracture [(] vf ) requires evidence of endplate fracture , and there is no minimum threshold for apparent ['] reduction ['] in vertebral height . 0 ###LEFT-WALL### 1 introduction 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 38 . 2 : 3 algorithm 2 : 18 requires 2 : 24 and 3 algorithm 10 definition 3 algorithm 18 requires 4 - 10 definition 5 based 10 definition 6 qualitative 8 abq 6 qualitative 10 definition 7 ( 8 abq 8 abq 9 ) 10 definition 11 of 10 definition 17 ) 11 of 16 vf 12 osteoporotic 14 fracture 13 vertebral 14 fracture 14 fracture 16 vf 18 requires 19 evidence 18 requires 22 fracture 19 evidence 20 of 20 of 21 endplate 23 , 24 and 24 and 25 there 24 and 26 is 25 there 26 is 26 is 29 threshold 27 no 29 threshold 28 minimum 29 threshold 29 threshold 30 for 30 for 33 reduction 31 apparent 33 reduction 33 reduction 35 in 35 in 37 height 36 vertebral 37 height in older women , svh without endplate [fracture] identified on baseline assessment may be long standing and unrelated to vf . 0 ###LEFT-WALL### 5 svh 0 ###LEFT-WALL### 14 be 0 ###LEFT-WALL### 21 . 1 in 3 women 1 in 4 , 1 in 5 svh 2 older 3 women 5 svh 6 without 5 svh 9 identified 5 svh 13 may 6 without 7 endplate 9 identified 10 on 10 on 12 assessment 11 baseline 12 assessment 13 may 14 be 14 be 15 long 14 be 17 and 16 standing 17 and 17 and 18 unrelated 18 unrelated 19 to 19 to 20 vf if this is so , we would expect to see a similar prevalence of svh in younger women . 0 ###LEFT-WALL### 6 we 0 ###LEFT-WALL### 8 expect 0 ###LEFT-WALL### 19 . 1 if 2 this 1 if 3 is 1 if 5 , 1 if 6 we 2 this 3 is 3 is 4 so 6 we 7 would 7 would 8 expect 8 expect 9 to 8 expect 10 see 9 to 10 see 10 see 13 prevalence 10 see 16 in 11 a 12 similar 11 a 13 prevalence 12 similar 13 prevalence 13 prevalence 14 of 14 of 15 svh 16 in 18 women 17 younger 18 women we aimed to compare the prevalence of pre - and postmenopausal women with svh and the characteristics of women [with] and without svh . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 aimed 0 ###LEFT-WALL### 24 . 1 we 2 aimed 2 aimed 3 to 2 aimed 4 compare 3 to 4 compare 4 compare 10 and 4 compare 21 and 5 the 10 and 6 prevalence 7 of 6 prevalence 10 and 7 of 8 pre 9 - 10 and 10 and 12 women 11 postmenopausal 12 women 13 with 15 and 13 with 21 and 14 svh 15 and 15 and 17 characteristics 15 and 18 of 16 the 17 characteristics 18 of 19 women 21 and 22 without 22 without 23 svh methods : we used the abq method to classify baseline vertebral images ( dxa - based imaging ) from 257 premenopausal and 1,361 postmenopausal women participating in the population - based osteoporosis and ultrasound study . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 31 based 0 ###LEFT-WALL### 36 . 2 : 3 we 2 : 4 used 3 we 4 used 4 used 7 method 4 used 8 to 4 used 9 classify 5 the 7 method 6 abq 7 method 8 to 9 classify 9 classify 12 images 9 classify 15 - 9 classify 19 from 10 baseline 12 images 11 vertebral 12 images 13 ( 15 - 14 dxa 15 - 15 - 17 imaging 15 - 18 ) 16 based 17 imaging 19 from 20 257 20 257 22 and 20 257 31 based 21 premenopausal 22 and 22 and 25 women 22 and 30 - 22 and 31 based 23 1,361 25 women 24 postmenopausal 25 women 25 women 26 participating 26 participating 27 in 27 in 29 population 28 the 29 population 31 based 35 study 32 osteoporosis 33 and 33 and 34 ultrasound 34 ultrasound 35 study images were classified as [follows] [:] normal ( no vf , no svh ) , svh ( no vf ) or vf ( with/without svh in unfractured vertebrae ) . 0 ###LEFT-WALL### 1 images 0 ###LEFT-WALL### 2 were 0 ###LEFT-WALL### 30 . 1 images 2 were 2 were 21 or 3 classified 4 as 3 classified 21 or 4 as 16 svh 7 normal 10 vf 7 normal 15 , 7 normal 16 svh 8 ( 10 vf 9 no 10 vf 10 vf 13 svh 10 vf 14 ) 11 , 13 svh 12 no 13 svh 13 svh 14 ) 16 svh 19 vf 17 ( 19 vf 18 no 19 vf 19 vf 20 ) 21 or 22 vf 21 or 25 svh 23 ( 25 svh 24 with/without 25 svh 25 svh 26 in 25 svh 29 ) 26 in 28 vertebrae 27 unfractured 28 vertebrae we compared proportions of women with svh ( chi - squared [test] ) and compared age , height , weight and bone mineral density ( bmd ) by abq classification ( two - sample [t] test/analysis of variance ) . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 14 and 0 ###LEFT-WALL### 40 . 1 we 14 and 2 compared 3 proportions 2 compared 11 squared 2 compared 14 and 3 proportions 4 of 3 proportions 9 chi 4 of 5 women 5 women 6 with 6 with 7 svh 8 ( 9 chi 9 chi 10 - 10 - 11 squared 11 squared 13 ) 14 and 15 compared 14 and 28 by 15 compared 16 age 16 age 21 and 17 , 21 and 18 height 19 , 19 , 20 weight 19 , 21 and 21 and 24 density 21 and 26 bmd 21 and 27 ) 22 bone 24 density 23 mineral 24 density 25 ( 26 bmd 26 bmd 27 ) 28 by 30 classification 29 abq 30 classification 30 classification 32 two 30 classification 36 test/analysis 31 ( 32 two 32 two 33 - 33 - 36 test/analysis 34 sample 36 test/analysis 36 test/analysis 37 of 36 test/analysis 39 ) 37 of 38 variance results : the prevalence of pre - and postmenopausal women with svh was 37 [%] and 33 % , respectively [(] p>0.05 ) . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 24 . 2 : 4 prevalence 2 : 13 was 3 the 4 prevalence 4 prevalence 5 of 4 prevalence 13 was 5 of 8 and 6 pre 8 and 7 - 8 and 8 and 10 women 8 and 11 with 9 postmenopausal 10 women 11 with 12 svh 13 was 18 % 14 37 16 and 16 and 17 33 16 and 18 % 18 % 22 p>0.05 19 , 20 respectively 19 , 22 p>0.05 22 p>0.05 23 ) compared to women without svh , premenopausal women with svh were older [(] p<0.001 [ )(and heavier [(] p=0.05 ) , and postmenopausal women with svh were [taller] ( p<0.05 ) , with higher spine bmd ( p<0.01 ) . 0 ###LEFT-WALL### 8 women 0 ###LEFT-WALL### 11 were 0 ###LEFT-WALL### 40 . 1 compared 2 to 1 compared 4 without 1 compared 6 , 1 compared 8 women 2 to 3 women 4 without 5 svh 7 premenopausal 8 women 8 women 9 with 8 women 11 were 9 with 10 svh 11 were 22 and 12 older 14 p<0.001 14 p<0.001 16 )(and 16 )(and 19 p=0.05 16 )(and 20 ) 16 )(and 22 and 17 heavier 19 p=0.05 21 , 22 and 22 and 23 postmenopausal 22 and 24 women 22 and 27 were 22 and 30 p<0.05 22 and 33 with 24 women 25 with 24 women 27 were 25 with 26 svh 29 ( 30 p<0.05 30 p<0.05 31 ) 32 , 33 with 33 with 36 bmd 33 with 39 ) 34 higher 35 spine 35 spine 36 bmd 36 bmd 38 p<0.01 37 ( 38 p<0.01 38 p<0.01 39 ) postmenopausal women with vf were older [(] p<0.001 [ )(and shorter [(] p<0.01 ) with lower bmd ( p<0.001 ) than women without vf . 0 ###LEFT-WALL### 2 women 0 ###LEFT-WALL### 5 were 0 ###LEFT-WALL### 25 . 1 postmenopausal 2 women 2 women 3 with 2 women 5 were 3 with 4 vf 5 were 10 )(and 5 were 15 with 5 were 21 than 5 were 23 without 6 older 8 p<0.001 8 p<0.001 10 )(and 10 )(and 13 p<0.01 10 )(and 14 ) 11 shorter 13 p<0.01 15 with 17 bmd 16 lower 17 bmd 17 bmd 19 p<0.001 18 ( 19 p<0.001 19 p<0.001 20 ) 21 than 22 women 23 without 24 vf conclusions : short vertebral height without endplate [fracture] is equally prevalent in pre - and postmenopausal women and not associated with low bone density . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 5 height 2 : 9 is 2 : 25 . 3 short 5 height 4 vertebral 5 height 5 height 6 without 5 height 9 is 6 without 7 endplate 9 is 10 equally 9 is 11 prevalent 11 prevalent 18 and 12 in 15 and 12 in 18 and 13 pre 15 and 14 - 15 and 15 and 17 women 16 postmenopausal 17 women 18 and 19 not 18 and 21 with 19 not 20 associated 21 with 24 density 22 low 24 density 23 bone 24 density neuronal activity enhances the elaboration of newborn neurons [as] they integrate into the synaptic circuitry of the adult brain . 0 ###LEFT-WALL### 2 activity 0 ###LEFT-WALL### 3 enhances 0 ###LEFT-WALL### 20 . 1 neuronal 2 activity 2 activity 3 enhances 3 enhances 5 elaboration 4 the 5 elaboration 5 elaboration 6 of 5 elaboration 10 they 5 elaboration 11 integrate 6 of 8 neurons 7 newborn 8 neurons 10 they 11 integrate 11 integrate 12 into 12 into 15 circuitry 13 the 15 circuitry 14 synaptic 15 circuitry 15 circuitry 16 of 16 of 19 brain 17 the 19 brain 18 adult 19 brain the role micrornas play in the transduction of neuronal activity into growth and synapse formation is largely unknown . 0 ###LEFT-WALL### 2 role 0 ###LEFT-WALL### 16 is 0 ###LEFT-WALL### 19 . 1 the 2 role 2 role 3 micrornas 2 role 13 and 2 role 16 is 3 micrornas 13 and 4 play 5 in 4 play 11 into 4 play 13 and 5 in 7 transduction 6 the 7 transduction 7 transduction 8 of 8 of 10 activity 9 neuronal 10 activity 11 into 12 growth 13 and 14 synapse 14 synapse 15 formation 16 is 18 unknown 17 largely 18 unknown micrornas can influence the expression of hundreds of genes and thus could regulate gene assemblies during processes like activity - dependent integration . 0 ###LEFT-WALL### 1 micrornas 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 20 - 1 micrornas 10 and 2 can 3 influence 2 can 10 and 3 influence 5 expression 4 the 5 expression 5 expression 6 of 6 of 9 genes 7 hundreds 8 of 7 hundreds 9 genes 8 of 9 genes 10 and 12 could 10 and 16 during 10 and 18 like 11 thus 12 could 12 could 13 regulate 13 regulate 15 assemblies 14 gene 15 assemblies 16 during 17 processes 18 like 19 activity 20 - 22 integration 20 - 23 . 21 dependent 22 integration here , we developed viral - based methods for [the] in vivo detection and manipulation of the activity - dependent microrna , mir - 132 , in the mouse hippocampus . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 23 mir 1 here 2 , 1 here 3 we 3 we 4 developed 4 developed 8 methods 4 developed 9 for 5 viral 6 - 5 viral 8 methods 7 based 8 methods 9 for 14 and 11 in 12 vivo 12 vivo 14 and 13 detection 14 and 14 and 15 manipulation 14 and 16 of 14 and 23 mir 16 of 18 activity 17 the 18 activity 18 activity 21 microrna 19 - 21 microrna 20 dependent 21 microrna 21 microrna 22 , 23 mir 25 132 24 - 25 132 25 132 27 in 26 , 27 in 27 in 30 hippocampus 27 in 31 . 28 the 30 hippocampus 29 mouse 30 hippocampus we find , using lentiviral and retroviral reporters of mir - 132 activity , that mir - 132 is expressed at the right place and right time to influence the integration of newborn neurons . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 25 and 0 ###LEFT-WALL### 35 . 1 we 25 and 2 find 4 using 2 find 18 132 2 find 20 expressed 2 find 25 and 3 , 4 using 4 using 6 and 4 using 17 - 5 lentiviral 6 and 6 and 8 reporters 6 and 9 of 7 retroviral 8 reporters 9 of 10 mir 10 mir 13 activity 11 - 13 activity 12 132 13 activity 13 activity 16 mir 13 activity 17 - 14 , 16 mir 15 that 16 mir 16 mir 17 - 18 132 19 is 19 is 20 expressed 20 expressed 21 at 21 at 24 place 22 the 24 place 23 right 24 place 25 and 26 right 25 and 27 time 27 time 28 to 27 time 29 influence 28 to 29 influence 29 influence 31 integration 30 the 31 integration 31 integration 32 of 32 of 34 neurons 33 newborn 34 neurons retroviral [knockdown] of mir - 132 using a specific ['] sponge ['] containing multiple target sequences impaired the integration of newborn neurons into the excitatory synaptic circuitry of the adult brain . 0 ###LEFT-WALL### 6 132 0 ###LEFT-WALL### 17 impaired 0 ###LEFT-WALL### 32 . 1 retroviral 6 132 3 of 4 mir 3 of 5 - 3 of 6 132 6 132 7 using 6 132 17 impaired 7 using 11 sponge 8 a 9 specific 8 a 11 sponge 9 specific 11 sponge 11 sponge 13 containing 13 containing 16 sequences 14 multiple 15 target 15 target 16 sequences 17 impaired 19 integration 17 impaired 23 into 18 the 19 integration 19 integration 20 of 20 of 22 neurons 21 newborn 22 neurons 23 into 27 circuitry 24 the 27 circuitry 25 excitatory 27 circuitry 26 synaptic 27 circuitry 27 circuitry 28 of 28 of 31 brain 29 the 31 brain 30 adult 31 brain to assess potential mir - 132 targets , we used a whole - genome microarray in pc12 cells , which have been used as a model of neuronal differentiation . mir - 132 knockdown in pc12 cells resulted in the increased expression of hundreds of genes . 0 ###LEFT-WALL### 9 we 0 ###LEFT-WALL### 10 used 0 ###LEFT-WALL### 19 , 0 ###LEFT-WALL### 30 . 1 to 2 assess 1 to 8 , 1 to 9 we 2 assess 7 targets 3 potential 7 targets 4 mir 5 - 4 mir 7 targets 6 132 7 targets 9 we 10 used 10 used 15 microarray 11 a 12 whole 11 a 15 microarray 12 whole 13 - 12 whole 14 genome 14 genome 15 microarray 15 microarray 16 in 16 in 18 cells 17 pc12 18 cells 19 , 20 which 19 , 23 used 20 which 21 have 21 have 22 been 22 been 23 used 23 used 24 as 24 as 26 model 25 a 26 model 26 model 27 of 27 of 29 differentiation 28 neuronal 29 differentiation 30 . 37 cells 30 . 38 resulted 30 . 47 . 31 mir 37 cells 32 - 33 132 33 132 35 in 34 knockdown 35 in 35 in 37 cells 36 pc12 37 cells 37 cells 38 resulted 38 resulted 39 in 39 in 42 expression 40 the 42 expression 41 increased 42 expression 42 expression 43 of 43 of 46 genes 44 hundreds 45 of 44 hundreds 46 genes 45 of 46 genes functional grouping indicated that genes involved in inflammatory/immune signaling were the most enriched class of genes induced by mir - 132 [knockdown] . 0 ###LEFT-WALL### 1 functional 0 ###LEFT-WALL### 13 enriched 0 ###LEFT-WALL### 20 - 0 ###LEFT-WALL### 23 . 1 functional 2 grouping 1 functional 3 indicated 1 functional 4 that 1 functional 10 were 1 functional 13 enriched 4 that 5 genes 4 that 10 were 5 genes 6 involved 5 genes 10 were 6 involved 7 in 7 in 8 inflammatory/immune 8 inflammatory/immune 9 signaling 10 were 12 most 11 the 12 most 13 enriched 14 class 13 enriched 18 by 14 class 15 of 14 class 17 induced 15 of 16 genes 18 by 19 mir 20 - 21 132 the correlation of [mir] - 132 knockdown to increased proinflammatory molecular expression may indicate a mechanistic link whereby mir [-] 132 functions as an endogenous mediator of activity [-] dependent integration in vivo . 0 ###LEFT-WALL### 2 correlation 0 ###LEFT-WALL### 14 indicate 0 ###LEFT-WALL### 34 . 1 the 2 correlation 2 correlation 3 of 2 correlation 13 may 3 of 6 132 5 - 6 132 6 132 7 knockdown 7 knockdown 8 to 8 to 12 expression 9 increased 12 expression 10 proinflammatory 12 expression 11 molecular 12 expression 13 may 14 indicate 14 indicate 17 link 14 indicate 18 whereby 14 indicate 33 vivo 15 a 16 mechanistic 15 a 17 link 16 mechanistic 17 link 18 whereby 19 mir 18 whereby 22 functions 19 mir 21 132 19 mir 22 functions 22 functions 23 as 23 as 26 mediator 24 an 26 mediator 25 endogenous 26 mediator 26 mediator 27 of 27 of 31 integration 28 activity 30 dependent 30 dependent 31 integration 32 in 33 vivo movement of individuals is a critical factor determining the effectiveness of reserve networks . 0 ###LEFT-WALL### 1 movement 0 ###LEFT-WALL### 4 is 0 ###LEFT-WALL### 14 . 1 movement 2 of 1 movement 4 is 2 of 3 individuals 4 is 7 factor 5 a 6 critical 5 a 7 factor 6 critical 7 factor 7 factor 8 determining 8 determining 10 effectiveness 8 determining 13 networks 9 the 10 effectiveness 10 effectiveness 11 of 10 effectiveness 13 networks 11 of 12 reserve marine reserves have historically been used for the management of species that are sedentary as adults , and , therefore , larval dispersal has been a major focus of marine - reserve research . 0 ###LEFT-WALL### 2 reserves 0 ###LEFT-WALL### 6 used 0 ###LEFT-WALL### 18 and 0 ###LEFT-WALL### 34 . 1 marine 2 reserves 2 reserves 3 have 3 have 5 been 4 historically 5 been 5 been 6 used 6 used 7 for 6 used 15 as 7 for 9 management 8 the 9 management 9 management 10 of 10 of 11 species 11 species 12 that 11 species 13 are 12 that 13 are 13 are 14 sedentary 15 as 16 adults 17 , 18 and 18 and 20 therefore 18 and 23 dispersal 18 and 25 been 19 , 20 therefore 20 therefore 21 , 22 larval 23 dispersal 23 dispersal 24 has 24 has 25 been 25 been 28 focus 26 a 27 major 26 a 28 focus 27 major 28 focus 28 focus 29 of 29 of 33 research 30 marine 31 - 30 marine 32 reserve 32 reserve 33 research the push to use marine reserves for managing pelagic and demersal species poses significant questions regarding their utility for highly [-] mobile species . 0 ###LEFT-WALL### 2 push 0 ###LEFT-WALL### 13 poses 0 ###LEFT-WALL### 24 . 1 the 2 push 2 push 3 to 2 push 8 managing 2 push 13 poses 3 to 4 use 4 use 6 reserves 5 marine 6 reserves 6 reserves 7 for 7 for 8 managing 8 managing 12 species 9 pelagic 10 and 10 and 11 demersal 10 and 12 species 13 poses 15 questions 13 poses 19 for 14 significant 15 questions 15 questions 16 regarding 16 regarding 18 utility 17 their 18 utility 19 for 23 species 20 highly 22 mobile 22 mobile 23 species here , a simple conceptual metapopulation model is developed to provide a rigorous comparison of the functioning of reserve networks for populations with different admixtures of larval dispersal and adult movement in a home range . 0 ###LEFT-WALL### 7 model 0 ###LEFT-WALL### 9 developed 0 ###LEFT-WALL### 36 . 1 here 2 , 1 here 7 model 3 a 4 simple 3 a 7 model 4 simple 6 metapopulation 5 conceptual 6 metapopulation 6 metapopulation 7 model 7 model 8 is 8 is 9 developed 9 developed 10 to 9 developed 21 for 9 developed 23 with 10 to 11 provide 11 provide 14 comparison 12 a 13 rigorous 12 a 14 comparison 13 rigorous 14 comparison 14 comparison 15 of 15 of 17 functioning 16 the 17 functioning 17 functioning 18 of 18 of 20 networks 19 reserve 20 networks 21 for 22 populations 23 with 29 and 23 with 32 in 24 different 25 admixtures 25 admixtures 26 of 25 admixtures 29 and 26 of 28 dispersal 27 larval 28 dispersal 29 and 31 movement 30 adult 31 movement 32 in 35 range 33 a 35 range 34 home 35 range we find that adult movement produces significantly lower persistence than larval dispersal , all other factors being equal . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 find 0 ###LEFT-WALL### 19 . 1 we 2 find 2 find 3 that 3 that 5 movement 3 that 6 produces 4 adult 5 movement 5 movement 6 produces 6 produces 9 persistence 6 produces 10 than 6 produces 17 being 7 significantly 8 lower 8 lower 9 persistence 10 than 12 dispersal 11 larval 12 dispersal 13 , 17 being 14 all 15 other 15 other 16 factors 16 factors 17 being 17 being 18 equal furthermore , redistribution of harvest effort previously [in] reserves to remaining fished areas ( ['] fishery squeeze ['] ) [and] fishing along reserve borders ( ['] fishing - the [-] line ['] ) considerably reduce persistence and harvests for populations mobile as adults , [while] [they] only [marginally] changes results for populations with dispersing larvae . 0 ###LEFT-WALL### 3 redistribution 0 ###LEFT-WALL### 9 reserves 1 furthermore 2 , 1 furthermore 3 redistribution 3 redistribution 4 of 3 redistribution 9 reserves 4 of 6 effort 5 harvest 6 effort 7 previously 9 reserves 9 reserves 10 to 9 reserves 21 fishing 10 to 13 areas 11 remaining 12 fished 12 fished 13 areas 13 areas 17 squeeze 14 ( 17 squeeze 16 fishery 17 squeeze 17 squeeze 19 ) 21 fishing 22 along 22 along 23 reserve 23 reserve 24 borders 23 reserve 35 reduce 24 borders 27 fishing 24 borders 31 line 24 borders 35 reduce 25 ( 27 fishing 27 fishing 28 - 28 - 31 line 29 the 31 line 31 line 33 ) 34 considerably 35 reduce 35 reduce 41 mobile 36 persistence 37 and 37 and 38 harvests 37 and 39 for 37 and 41 mobile 39 for 40 populations 41 mobile 42 as 41 mobile 50 results 42 as 43 adults 44 , 47 only 44 , 50 results 49 changes 50 results 50 results 51 for 50 results 56 . 51 for 52 populations 52 populations 53 with 53 with 54 dispersing 54 dispersing 55 larvae persistently elevated oxidative stress and inflammation [precede] or occur during the development of type 1 or type 2 diabetes mellitus and precipitate devastating complications . 0 ###LEFT-WALL### 8 or 0 ###LEFT-WALL### 25 . 1 persistently 2 elevated 2 elevated 5 and 2 elevated 8 or 3 oxidative 4 stress 4 stress 5 and 5 and 6 inflammation 8 or 16 or 9 occur 10 during 9 occur 16 or 10 during 12 development 11 the 12 development 12 development 13 of 13 of 14 type 14 type 15 1 16 or 17 type 17 type 21 and 18 2 21 and 19 diabetes 20 mellitus 20 mellitus 21 and 21 and 24 complications 22 precipitate 24 complications 23 devastating 24 complications given the rapidly increasing incidence of diabetes mellitus and obesity in the space of a few decades , new genetic mutations are unlikely to be the cause , instead pointing to environmental initiators . 0 ###LEFT-WALL### 21 mutations 0 ###LEFT-WALL### 22 are 0 ###LEFT-WALL### 34 . 1 given 5 incidence 1 given 11 in 1 given 18 , 1 given 21 mutations 2 the 5 incidence 3 rapidly 4 increasing 4 increasing 5 incidence 5 incidence 6 of 6 of 9 and 7 diabetes 8 mellitus 8 mellitus 9 and 9 and 10 obesity 11 in 13 space 12 the 13 space 13 space 14 of 14 of 17 decades 15 a 16 few 16 few 17 decades 19 new 21 mutations 20 genetic 21 mutations 21 mutations 22 are 22 are 23 unlikely 23 unlikely 24 to 23 unlikely 31 to 24 to 28 , 25 be 27 cause 25 be 28 , 26 the 27 cause 28 , 30 pointing 29 instead 30 pointing 31 to 33 initiators 32 environmental 33 initiators a hallmark of contemporary culture is a preference for thermally processed foods , replete with pro [-] oxidant advanced glycation endproducts ( ages ) . 0 ###LEFT-WALL### 2 hallmark 0 ###LEFT-WALL### 6 is 0 ###LEFT-WALL### 25 . 1 a 2 hallmark 2 hallmark 3 of 2 hallmark 6 is 3 of 5 culture 4 contemporary 5 culture 6 is 8 preference 7 a 8 preference 8 preference 9 for 9 for 12 foods 10 thermally 11 processed 11 processed 12 foods 12 foods 14 replete 13 , 14 replete 14 replete 15 with 14 replete 24 ) 15 with 21 endproducts 16 pro 18 oxidant 18 oxidant 21 endproducts 19 advanced 20 glycation 20 glycation 21 endproducts 21 endproducts 23 ages 22 ( 23 ages 23 ages 24 ) these molecules are [appetite] - increasing and , thus , efficient enhancers of overnutrition ( which promotes obesity ) and oxidant [overload] ( which promotes inflammation ) . 0 ###LEFT-WALL### 2 molecules 0 ###LEFT-WALL### 3 are 0 ###LEFT-WALL### 5 - 1 these 2 molecules 2 molecules 3 are 5 - 20 and 5 - 28 . 6 increasing 7 and 7 and 9 thus 7 and 11 efficient 7 and 12 enhancers 8 , 9 thus 9 thus 10 , 12 enhancers 13 of 12 enhancers 20 and 13 of 14 overnutrition 14 overnutrition 16 which 15 ( 16 which 16 which 17 promotes 16 which 19 ) 17 promotes 18 obesity 20 and 21 oxidant 20 and 24 which 23 ( 24 which 24 which 25 promotes 24 which 27 ) 25 promotes 26 inflammation studies of genetic and nongenetic animal models of diabetes mellitus suggest that suppression of host defenses , under sustained pressure from food - derived ages , may potentially shift homeostasis towards a higher basal level of oxidative stress , inflammation and injury of both insulin - producing and insulin - responsive cells . 0 ###LEFT-WALL### 1 studies 0 ###LEFT-WALL### 26 , 0 ###LEFT-WALL### 53 . 1 studies 2 of 1 studies 26 , 2 of 7 models 3 genetic 4 and 4 and 5 nongenetic 4 and 7 models 6 animal 7 models 7 models 8 of 8 of 10 mellitus 9 diabetes 10 mellitus 11 suggest 12 that 11 suggest 26 , 12 that 13 suppression 12 that 24 derived 13 suppression 14 of 13 suppression 24 derived 14 of 16 defenses 15 host 16 defenses 16 defenses 18 under 17 , 18 under 18 under 20 pressure 18 under 23 - 19 sustained 20 pressure 20 pressure 21 from 21 from 22 food 24 derived 25 ages 26 , 27 may 26 , 52 cells 27 may 29 shift 28 potentially 29 shift 29 shift 30 homeostasis 29 shift 31 towards 31 towards 35 level 32 a 35 level 33 higher 35 level 34 basal 35 level 35 level 36 of 36 of 45 insulin 37 oxidative 45 insulin 38 stress 39 , 39 , 40 inflammation 39 , 41 and 41 and 42 injury 41 and 45 insulin 42 injury 43 of 43 of 44 both 45 insulin 48 and 46 - 48 and 47 producing 48 and 48 and 49 insulin 48 and 50 - 51 responsive 52 cells this sequence promotes both types of diabetes mellitus . 0 ###LEFT-WALL### 2 sequence 0 ###LEFT-WALL### 3 promotes 0 ###LEFT-WALL### 9 . 1 this 2 sequence 2 sequence 3 promotes 3 promotes 8 mellitus 4 both 5 types 5 types 6 of 5 types 8 mellitus 6 of 8 mellitus 7 diabetes 8 mellitus reducing basal oxidative stress by age [restriction] in mice , without energy or nutrient change , reinstates host defenses , alleviates inflammation , prevents diabetes mellitus , vascular and renal complications and extends normal lifespan . 0 ###LEFT-WALL### 1 reducing 0 ###LEFT-WALL### 20 , 0 ###LEFT-WALL### 36 . 1 reducing 4 stress 1 reducing 8 in 1 reducing 20 , 2 basal 4 stress 3 oxidative 4 stress 4 stress 5 by 5 by 6 age 8 in 9 mice 9 mice 11 without 10 , 11 without 11 without 13 or 11 without 16 , 12 energy 13 or 13 or 15 change 14 nutrient 15 change 17 reinstates 19 defenses 17 reinstates 20 , 18 host 19 defenses 20 , 23 , 21 alleviates 22 inflammation 21 alleviates 23 , 23 , 32 and 24 prevents 29 and 24 prevents 32 and 25 diabetes 26 mellitus 26 mellitus 27 , 27 , 28 vascular 27 , 29 and 29 and 31 complications 30 renal 31 complications 32 and 33 extends 33 extends 35 lifespan 34 normal 35 lifespan studies in healthy humans and in those with diabetes mellitus show that consumption of high amounts of food - related ages is a determinant of insulin resistance and inflammation and that age restriction improves both . 0 ###LEFT-WALL### 1 studies 0 ###LEFT-WALL### 11 show 0 ###LEFT-WALL### 30 and 0 ###LEFT-WALL### 36 . 1 studies 5 and 1 studies 11 show 2 in 4 humans 2 in 5 and 3 healthy 4 humans 5 and 6 in 6 in 7 those 7 those 8 with 8 with 10 mellitus 9 diabetes 10 mellitus 11 show 12 that 12 that 13 consumption 12 that 22 is 13 consumption 14 of 13 consumption 22 is 14 of 16 amounts 15 high 16 amounts 16 amounts 17 of 17 of 18 food 19 - 20 related 20 related 21 ages 20 related 22 is 22 is 24 determinant 23 a 24 determinant 24 determinant 25 of 25 of 28 and 26 insulin 27 resistance 27 resistance 28 and 28 and 29 inflammation 30 and 33 restriction 30 and 34 improves 31 that 33 restriction 32 age 33 restriction 33 restriction 34 improves 34 improves 35 both this review focuses on ages as novel initiators of oxidative stress that precedes , rather than results [from] , diabetes mellitus . 0 ###LEFT-WALL### 2 review 0 ###LEFT-WALL### 3 focuses 0 ###LEFT-WALL### 22 . 1 this 2 review 2 review 3 focuses 3 focuses 4 on 3 focuses 6 as 4 on 5 ages 6 as 8 initiators 7 novel 8 initiators 8 initiators 9 of 9 of 11 stress 10 oxidative 11 stress 11 stress 12 that 11 stress 13 precedes 12 that 13 precedes 13 precedes 16 than 13 precedes 21 mellitus 14 , 16 than 15 rather 16 than 16 than 17 results 16 than 19 , 20 diabetes 21 mellitus therapeutic gains from age [restriction] constitute a paradigm shift . 0 ###LEFT-WALL### 2 gains 0 ###LEFT-WALL### 6 constitute 0 ###LEFT-WALL### 10 . 1 therapeutic 2 gains 2 gains 3 from 2 gains 6 constitute 3 from 4 age 6 constitute 9 shift 7 a 9 shift 8 paradigm 9 shift objective : the age - dependent performance of electrocardiographic ( ecg ) criteria was examined for left [ventricular] [hypertrophy] ( lvh ) prediction . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 5 - 1 objective 2 : 2 : 4 age 3 the 4 age 5 - 7 performance 5 - 15 examined 5 - 24 . 6 dependent 7 performance 7 performance 8 of 7 performance 14 was 8 of 13 criteria 9 electrocardiographic 11 ecg 9 electrocardiographic 13 criteria 10 ( 11 ecg 11 ecg 12 ) 14 was 15 examined 15 examined 16 for 16 for 23 prediction 17 left 21 lvh 17 left 23 prediction 20 ( 21 lvh 21 lvh 22 ) methods : during 2009 , 570 middle - aged [(] 54 ± 7 years , 45 % men ) and 507 elderly ( 75 ± 6 years , 45 % men ) inhabitants of the ikaria island were studied . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 5 , 1 methods 2 : 2 : 3 during 3 during 4 2009 5 , 7 middle 5 , 8 - 6 570 7 middle 8 - 20 and 8 - 39 studied 8 - 40 . 9 aged 12 ± 11 54 12 ± 12 ± 14 years 13 7 14 years 14 years 18 men 14 years 20 and 15 , 18 men 16 45 17 % 17 % 18 men 18 men 19 ) 20 and 33 inhabitants 20 and 34 of 20 and 38 were 21 507 33 inhabitants 22 elderly 27 years 22 elderly 33 inhabitants 23 ( 27 years 24 75 27 years 25 ± 27 years 26 6 27 years 27 years 31 men 27 years 32 ) 28 , 31 men 29 45 30 % 30 % 31 men 31 men 32 ) 34 of 37 island 35 the 37 island 36 ikaria 37 island 38 were 39 studied results : the framingham criteria had in hierarchical order the highest , although insignificant , sensitivity among the elderly individuals , [either] [when] lvh was indexed for bsa or for height ( 18.4 and 16.7 % , respectively ) . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 5 criteria 2 : 26 indexed 2 : 40 . 3 the 5 criteria 4 framingham 5 criteria 5 criteria 6 had 6 had 7 in 6 had 11 highest 6 had 13 although 7 in 9 order 8 hierarchical 9 order 10 the 11 highest 12 , 13 although 13 although 24 lvh 14 insignificant 16 sensitivity 14 insignificant 21 , 14 insignificant 24 lvh 15 , 16 sensitivity 16 sensitivity 17 among 16 sensitivity 21 , 17 among 20 individuals 18 the 20 individuals 19 elderly 20 individuals 24 lvh 25 was 25 was 26 indexed 26 indexed 29 or 26 indexed 38 respectively 27 for 28 bsa 27 for 29 or 29 or 30 for 30 for 31 height 31 height 36 % 32 ( 36 % 33 18.4 34 and 34 and 35 16.7 34 and 36 % 36 % 37 , 37 , 38 respectively 38 respectively 39 ) cornell voltage and product criteria had hierarchically the highest sensitivity [among] middle - aged participants , either when lvh was indexed for bsa ( 19.0 and 23.8 % , respectively ) [or] for height ( 17.2 and 20.3 % , respectively ) . 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 43 . 1 cornell 2 voltage 2 voltage 3 and 3 and 5 criteria 3 and 6 had 4 product 5 criteria 6 had 7 hierarchically 6 had 12 middle 6 had 17 either 6 had 18 when 8 the 9 highest 8 the 12 middle 10 sensitivity 12 middle 12 middle 15 participants 13 - 15 participants 14 aged 15 participants 15 participants 16 , 18 when 19 lvh 18 when 21 indexed 19 lvh 20 was 20 was 21 indexed 21 indexed 22 for 21 indexed 30 respectively 21 indexed 33 for 21 indexed 41 respectively 22 for 23 bsa 23 bsa 28 % 24 ( 28 % 25 19.0 26 and 26 and 27 23.8 26 and 28 % 28 % 29 , 29 , 30 respectively 30 respectively 31 ) 33 for 34 height 34 height 39 % 35 ( 39 % 36 17.2 37 and 37 and 38 20.3 37 and 39 % 39 % 40 , 40 , 41 respectively 41 respectively 42 ) in the multiadjusted analysis applied in elderly participants , cornell voltage , its product and framingham criteria were associated with echocardiographic detection of lvh ( indexed for bsa ) ; however , when lvh was indexed for height , the sokolow - lyon and framingham criteria were associated with lvh detection . 0 ###LEFT-WALL### 17 criteria 0 ###LEFT-WALL### 19 associated 0 ###LEFT-WALL### 30 ; 0 ###LEFT-WALL### 52 . 1 in 15 and 1 in 17 criteria 2 the 4 analysis 3 multiadjusted 4 analysis 4 analysis 5 applied 4 analysis 6 in 4 analysis 9 , 6 in 8 participants 7 elderly 8 participants 9 , 11 voltage 9 , 12 , 10 cornell 11 voltage 12 , 14 product 12 , 15 and 13 its 14 product 15 and 16 framingham 17 criteria 18 were 18 were 19 associated 19 associated 20 with 19 associated 26 indexed 20 with 22 detection 21 echocardiographic 22 detection 22 detection 23 of 23 of 24 lvh 25 ( 26 indexed 26 indexed 27 for 26 indexed 29 ) 27 for 28 bsa 30 ; 44 and 30 ; 48 associated 31 however 44 and 32 , 33 when 33 when 34 lvh 33 when 36 indexed 33 when 42 - 33 when 44 and 34 lvh 35 was 35 was 36 indexed 36 indexed 37 for 37 for 38 height 38 height 41 sokolow 39 , 41 sokolow 40 the 41 sokolow 41 sokolow 42 - 43 lyon 44 and 44 and 46 criteria 44 and 47 were 45 framingham 46 criteria 47 were 48 associated 48 associated 49 with 49 with 50 lvh 49 with 51 detection in contrast , among middle [-] aged individuals , the cornell product was the only ecg criterion that was associated with lvh detection ( irrespective of indexation ) . 0 ###LEFT-WALL### 12 product 0 ###LEFT-WALL### 13 was 0 ###LEFT-WALL### 29 . 1 in 2 contrast 1 in 9 , 1 in 12 product 2 contrast 4 among 3 , 4 among 4 among 8 individuals 4 among 9 , 5 middle 7 aged 7 aged 8 individuals 10 the 12 product 11 cornell 12 product 12 product 13 was 13 was 17 criterion 14 the 15 only 14 the 17 criterion 16 ecg 17 criterion 17 criterion 18 that 17 criterion 19 was 18 that 19 was 19 was 20 associated 20 associated 21 with 20 associated 26 of 21 with 23 detection 22 lvh 23 detection 24 ( 26 of 25 irrespective 26 of 26 of 27 indexation 26 of 28 ) conclusion : age should be taken into consideration in selection of appropriate ecg criteria for lvh detection . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 3 age 2 : 6 taken 2 : 18 . 3 age 4 should 4 should 5 be 5 be 6 taken 6 taken 7 into 6 taken 9 in 7 into 8 consideration 9 in 10 selection 10 selection 11 of 11 of 14 criteria 12 appropriate 14 criteria 13 ecg 14 criteria 14 criteria 15 for 15 for 17 detection 16 lvh 17 detection indexation [of] left [ventricular] [mass] differentiates the diagnostic ability of ecg criteria , especially in older patients . 0 ###LEFT-WALL### 1 indexation 0 ###LEFT-WALL### 6 differentiates 1 indexation 3 left 1 indexation 6 differentiates 6 differentiates 9 ability 7 the 9 ability 8 diagnostic 9 ability 9 ability 10 of 10 of 12 criteria 11 ecg 12 criteria 12 criteria 15 in 13 , 14 especially 13 , 15 in 15 in 17 patients 15 in 18 . 16 older 17 patients purpose : recent studies have revealed that the majority of pediatric low - grade astrocytomas ( plga ) harbor the braf - kiaa1549 ( b - k ) fusion gene resulting in constitutive activation of the ras/mapk pathway . 0 ###LEFT-WALL### 1 purpose 0 ###LEFT-WALL### 2 : 2 : 4 studies 2 : 6 revealed 2 : 39 . 3 recent 4 studies 4 studies 5 have 5 have 6 revealed 6 revealed 7 that 7 that 9 majority 7 that 19 harbor 8 the 9 majority 9 majority 10 of 9 majority 17 plga 9 majority 19 harbor 10 of 15 astrocytomas 11 pediatric 14 grade 12 low 13 - 12 low 14 grade 14 grade 15 astrocytomas 16 ( 17 plga 17 plga 18 ) 19 harbor 30 gene 20 the 30 gene 21 braf 23 kiaa1549 21 braf 30 gene 22 - 23 kiaa1549 23 kiaa1549 26 - 23 kiaa1549 28 ) 24 ( 26 - 25 b 26 - 26 - 27 k 26 - 28 ) 29 fusion 30 gene 30 gene 31 resulting 31 resulting 32 in 32 in 34 activation 33 constitutive 34 activation 34 activation 35 of 35 of 38 pathway 36 the 38 pathway 37 ras/mapk 38 pathway however , the clinical significance of this genetic alteration is yet to be determined . 0 ###LEFT-WALL### 5 significance 0 ###LEFT-WALL### 15 . 1 however 2 , 1 however 5 significance 3 the 5 significance 4 clinical 5 significance 5 significance 6 of 5 significance 10 is 6 of 9 alteration 7 this 8 genetic 8 genetic 9 alteration 10 is 11 yet 10 is 12 to 10 is 13 be 12 to 13 be 13 be 14 determined we aimed to test the prognostic role of the b - k fusion in progression of incompletely resected plga . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 aimed 0 ###LEFT-WALL### 20 . 1 we 2 aimed 2 aimed 3 to 2 aimed 4 test 3 to 4 test 4 test 7 role 4 test 14 in 5 the 7 role 6 prognostic 7 role 7 role 8 of 8 of 13 fusion 9 the 13 fusion 10 b 11 - 11 - 12 k 11 - 13 fusion 14 in 15 progression 15 progression 16 of 16 of 19 plga 17 incompletely 18 resected 18 resected 19 plga experimental design : we retrospectively identified 70 consecutive patients with incompletely resected " clinically relevant " plga . 0 ###LEFT-WALL### 2 design 0 ###LEFT-WALL### 3 : 1 experimental 2 design 3 : 4 we 3 : 6 identified 3 : 18 . 4 we 6 identified 5 retrospectively 6 identified 6 identified 9 patients 6 identified 10 with 7 70 9 patients 8 consecutive 9 patients 10 with 17 plga 11 incompletely 12 resected 12 resected 13 " 12 resected 17 plga 14 clinically 15 relevant 15 relevant 16 " 15 relevant 17 plga we added 76 tumors diagnosed at our institution between 1985 and 2010 as controls . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 added 0 ###LEFT-WALL### 15 . 1 we 2 added 2 added 4 tumors 3 76 4 tumors 4 tumors 5 diagnosed 5 diagnosed 6 at 5 diagnosed 9 between 5 diagnosed 13 as 6 at 8 institution 7 our 8 institution 9 between 11 and 10 1985 11 and 11 and 12 2010 13 as 14 controls we examined braf alterations by reverse transcriptase pcr , fish , and single - nucleotide polymorphism array analysis and correlated that with progression - free survival ( pfs ) . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 19 and 0 ###LEFT-WALL### 30 . 1 we 19 and 2 examined 12 and 2 examined 17 array 2 examined 19 and 3 braf 4 alterations 4 alterations 5 by 4 alterations 9 , 5 by 8 pcr 6 reverse 8 pcr 7 transcriptase 8 pcr 9 , 10 fish 9 , 12 and 11 , 12 and 12 and 16 polymorphism 12 and 17 array 13 single 14 - 13 single 15 nucleotide 15 nucleotide 16 polymorphism 17 array 18 analysis 19 and 20 correlated 19 and 22 with 20 correlated 21 that 22 with 23 progression 23 progression 26 survival 24 - 26 survival 25 free 26 survival 26 survival 28 pfs 26 survival 29 ) 27 ( 28 pfs 28 pfs 29 ) results : overall , 60 % of tumors were b - k fusion [positive] . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 4 , 0 ###LEFT-WALL### 15 . 1 results 2 : 2 : 3 overall 4 , 6 % 4 , 9 were 5 60 6 % 6 % 7 of 6 % 9 were 7 of 8 tumors 9 were 13 fusion 10 b 11 - 11 - 12 k 11 - 13 fusion all patients with b - k fused plga are still alive . 0 ###LEFT-WALL### 2 patients 0 ###LEFT-WALL### 9 are 0 ###LEFT-WALL### 12 . 1 all 2 patients 2 patients 3 with 2 patients 9 are 3 with 8 plga 4 b 5 - 5 - 6 k 5 - 7 fused 7 fused 8 plga 9 are 10 still 9 are 11 alive five - year pfs was 61 % ± 8 % and 18 % ± 8 % for fusion positive and negative patients , respectively ( p = 0.0004 ) . 0 ###LEFT-WALL### 1 five 0 ###LEFT-WALL### 2 - 0 ###LEFT-WALL### 30 . 2 - 4 pfs 2 - 5 was 3 year 4 pfs 4 pfs 5 was 5 was 20 and 5 was 24 respectively 5 was 27 = 6 61 7 % 6 61 11 and 7 % 8 ± 8 ± 10 % 9 8 10 % 11 and 12 18 11 and 20 and 12 18 13 % 13 % 14 ± 14 ± 16 % 14 ± 17 for 15 8 16 % 17 for 18 fusion 19 positive 20 and 20 and 22 patients 20 and 23 , 21 negative 22 patients 25 ( 27 = 26 p 27 = 27 = 28 0.0004 27 = 29 ) b - k fusion resulted in similarly significant favorable pfs for patients who received chemotherapy . 0 ###LEFT-WALL### 4 fusion 0 ###LEFT-WALL### 5 resulted 0 ###LEFT-WALL### 16 . 1 b 2 - 2 - 3 k 2 - 4 fusion 4 fusion 5 resulted 5 resulted 6 in 6 in 10 pfs 7 similarly 8 significant 8 significant 10 pfs 9 favorable 10 pfs 10 pfs 11 for 11 for 12 patients 12 patients 13 who 12 patients 14 received 13 who 14 received 14 received 15 chemotherapy multivariate analysis revealed that b - k fusion was the most significant favorable prognostic factor in incompletely resected plga and was independent of location [,] pathology , and age . 0 ###LEFT-WALL### 2 analysis 0 ###LEFT-WALL### 3 revealed 0 ###LEFT-WALL### 30 . 1 multivariate 2 analysis 2 analysis 3 revealed 3 revealed 4 that 4 that 8 fusion 4 that 20 and 5 b 6 - 6 - 7 k 6 - 8 fusion 8 fusion 20 and 9 was 15 factor 9 was 20 and 10 the 15 factor 11 most 12 significant 12 significant 15 factor 13 favorable 15 factor 14 prognostic 15 factor 15 factor 16 in 16 in 19 plga 17 incompletely 18 resected 18 resected 19 plga 20 and 21 was 21 was 28 and 22 independent 23 of 22 independent 28 and 23 of 26 pathology 24 location 26 pathology 27 , 28 and 28 and 29 age in vitro , braf overexpression resulted in growth arrest associated with dna damage ( γh2ax expression ) . 0 ###LEFT-WALL### 5 overexpression 0 ###LEFT-WALL### 6 resulted 0 ###LEFT-WALL### 18 . 1 in 2 vitro 2 vitro 3 , 2 vitro 5 overexpression 4 braf 5 overexpression 5 overexpression 6 resulted 6 resulted 7 in 7 in 9 arrest 8 growth 9 arrest 9 arrest 10 associated 10 associated 11 with 11 with 13 damage 12 dna 13 damage 13 damage 16 expression 14 ( 16 expression 15 γh2ax 16 expression 16 expression 17 ) five - year pfs was 68 % ± 15 % and 0 % for patients with b - k fused and γh2ax - expressing plga versus negative tumors ( p = 0.001 ) . 0 ###LEFT-WALL### 1 five 0 ###LEFT-WALL### 2 - 2 - 4 pfs 2 - 5 was 2 - 34 . 3 year 4 pfs 4 pfs 5 was 5 was 13 % 6 68 7 % 6 68 11 and 7 % 8 ± 8 ± 10 % 9 15 10 % 11 and 12 0 11 and 13 % 13 % 14 for 13 % 24 expressing 14 for 15 patients 15 patients 16 with 15 patients 21 and 16 with 17 b 18 - 21 and 19 k 20 fused 19 k 21 and 21 and 22 γh2ax 21 and 23 - 24 expressing 25 plga 25 plga 26 versus 25 plga 31 = 26 versus 28 tumors 27 negative 28 tumors 29 ( 31 = 30 p 31 = 31 = 32 0.001 31 = 33 ) conclusion : these data suggest that b - k fusion confers a less aggressive clinical phenotype on plga and may explain their tendency to growth arrest . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 4 data 2 : 19 and 2 : 27 . 3 these 4 data 4 data 19 and 5 suggest 6 that 5 suggest 19 and 6 that 10 fusion 6 that 11 confers 7 b 8 - 8 - 9 k 8 - 10 fusion 10 fusion 11 confers 11 confers 16 phenotype 11 confers 17 on 12 a 16 phenotype 13 less 14 aggressive 14 aggressive 16 phenotype 15 clinical 16 phenotype 17 on 18 plga 19 and 20 may 19 and 24 to 19 and 26 arrest 20 may 21 explain 21 explain 23 tendency 22 their 23 tendency 24 to 25 growth combined analysis of b - k fusion and γh2ax expression can determine [prognosis] and may be a powerful tool to tailor therapy for these patients . 0 ###LEFT-WALL### 14 and 0 ###LEFT-WALL### 26 . 1 combined 2 analysis 1 combined 14 and 2 analysis 3 of 3 of 8 and 4 b 5 - 5 - 6 k 5 - 7 fusion 7 fusion 8 and 8 and 9 γh2ax 8 and 10 expression 8 and 12 determine 10 expression 11 can 11 can 12 determine 14 and 15 may 15 may 16 be 16 be 19 tool 17 a 18 powerful 17 a 19 tool 18 powerful 19 tool 19 tool 20 to 19 tool 23 for 20 to 22 therapy 21 tailor 22 therapy 23 for 25 patients 24 these 25 patients background : physical functioning describes the underlying abilities that make activities necessary for independent living in the community possible . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 4 functioning 2 : 5 describes 2 : 20 . 3 physical 4 functioning 4 functioning 5 describes 5 describes 8 abilities 6 the 8 abilities 7 underlying 8 abilities 8 abilities 9 that 8 abilities 10 make 9 that 10 make 10 make 11 activities 10 make 19 possible 11 activities 12 necessary 12 necessary 13 for 12 necessary 16 in 13 for 15 living 14 independent 15 living 16 in 18 community 17 the 18 community objective : [to] test self - reported [and] objective measures of physical functioning in predicting subsequent disability in cooking , shopping and housework . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 24 . 2 : 5 self 2 : 7 reported 4 test 5 self 6 - 7 reported 7 reported 10 measures 7 reported 14 in 7 reported 18 in 9 objective 10 measures 10 measures 11 of 11 of 13 functioning 12 physical 13 functioning 14 in 15 predicting 15 predicting 17 disability 16 subsequent 17 disability 18 in 22 and 19 cooking 20 , 20 , 21 shopping 20 , 22 and 22 and 23 housework design : we used data from the first and second waves of the survey of health , ageing and retirement in europe . 0 ###LEFT-WALL### 1 design 0 ###LEFT-WALL### 2 : 2 : 3 we 2 : 9 and 2 : 23 . 3 we 9 and 4 used 5 data 4 used 6 from 4 used 9 and 6 from 8 first 7 the 8 first 9 and 10 second 10 second 11 waves 10 second 21 in 11 waves 12 of 11 waves 15 of 12 of 14 survey 13 the 14 survey 15 of 19 and 16 health 17 , 17 , 18 ageing 17 , 19 and 19 and 20 retirement 21 in 22 europe the respondents were asked about physical functioning ( climbing , pulling/pushing , stooping/crouching/kneeling , lifting/carrying and reaching/extending were comparable [ )(and they had their grip strength and walking speed measured . 0 ###LEFT-WALL### 2 respondents 0 ###LEFT-WALL### 4 asked 0 ###LEFT-WALL### 10 , 0 ###LEFT-WALL### 31 . 1 the 2 respondents 2 respondents 3 were 3 were 4 asked 4 asked 5 about 5 about 7 functioning 6 physical 7 functioning 7 functioning 9 climbing 8 ( 9 climbing 9 climbing 10 , 10 , 16 and 10 , 18 were 11 pulling/pushing 12 , 12 , 13 stooping/crouching/kneeling 12 , 14 , 14 , 15 lifting/carrying 14 , 16 and 16 and 17 reaching/extending 16 and 18 were 18 were 21 )(and 19 comparable 21 )(and 21 )(and 22 they 21 )(and 27 and 21 )(and 30 measured 23 had 26 strength 23 had 27 and 24 their 26 strength 25 grip 26 strength 27 and 28 walking 27 and 29 speed participants : men and women aged 65 years or over who reported no disability in cooking , shopping and housework at baseline were included in the analysis . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 28 . 2 : 4 and 2 : 6 aged 2 : 9 or 3 men 4 and 4 and 5 women 4 and 6 aged 6 aged 8 years 7 65 8 years 9 or 19 and 9 or 24 included 10 over 11 who 10 over 17 , 10 over 19 and 11 who 12 reported 12 reported 14 disability 12 reported 15 in 13 no 14 disability 15 in 16 cooking 18 shopping 19 and 19 and 20 housework 19 and 21 at 19 and 23 were 21 at 22 baseline 23 were 24 included 24 included 25 in 25 in 27 analysis 26 the 27 analysis there were 6,841 individuals for whom data on disability status at [follow] - up were available . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 were 0 ###LEFT-WALL### 17 . 1 there 2 were 2 were 4 individuals 3 6,841 4 individuals 4 individuals 5 for 5 for 6 whom 5 for 7 data 5 for 15 were 7 data 8 on 7 data 11 at 7 data 15 were 8 on 10 status 9 disability 10 status 11 at 14 up 13 - 14 up 15 were 16 available methods : poisson regression was used to calculate relative risks for the associations between [self] - reported [and] objective measures of physical functioning with disability at 2 years , adjusting for age , gender , educational level , cognitive function and chronic conditions . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 8 calculate 0 ###LEFT-WALL### 44 . 2 : 4 regression 2 : 6 used 3 poisson 4 regression 4 regression 5 was 5 was 6 used 6 used 7 to 7 to 8 calculate 8 calculate 10 risks 8 calculate 14 between 8 calculate 31 for 9 relative 10 risks 10 risks 11 for 11 for 13 associations 12 the 13 associations 14 between 30 adjusting 16 - 17 reported 17 reported 20 measures 17 reported 29 , 17 reported 30 adjusting 19 objective 20 measures 20 measures 21 of 21 of 23 functioning 22 physical 23 functioning 23 functioning 24 with 23 functioning 26 at 24 with 25 disability 26 at 28 years 27 2 28 years 31 for 41 and 32 age 33 , 33 , 34 gender 33 , 35 , 35 , 40 function 35 , 41 and 36 educational 40 function 37 level 38 , 37 level 40 function 39 cognitive 40 function 41 and 43 conditions 42 chronic 43 conditions results : those with limitations in physical functioning at baseline more frequently reported subsequent disability . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 3 those 2 : 13 reported 2 : 16 . 3 those 4 with 3 those 13 reported 4 with 5 limitations 5 limitations 6 in 6 in 8 functioning 7 physical 8 functioning 8 functioning 9 at 9 at 10 baseline 11 more 12 frequently 12 frequently 13 reported 13 reported 15 disability 14 subsequent 15 disability [walking] ability was most strongly associated with disability ; climbing , pulling/pushing , lifting/carrying and reaching/extending were comparable ( picking [was] [non] - significant ) . 0 ###LEFT-WALL### 2 ability 0 ###LEFT-WALL### 3 was 0 ###LEFT-WALL### 9 ; 0 ###LEFT-WALL### 26 . 2 ability 3 was 3 was 4 most 4 most 6 associated 5 strongly 6 associated 6 associated 7 with 7 with 8 disability 9 ; 15 and 9 ; 17 were 10 climbing 11 , 10 climbing 15 and 12 pulling/pushing 13 , 13 , 14 lifting/carrying 13 , 15 and 15 and 16 reaching/extending 15 and 17 were 17 were 18 comparable 18 comparable 20 picking 19 ( 20 picking 20 picking 23 - 20 picking 24 significant 20 picking 25 ) similar results were obtained with grip strength and walking speed . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 10 speed 0 ###LEFT-WALL### 11 . 1 similar 2 results 2 results 8 and 2 results 10 speed 3 were 4 obtained 3 were 8 and 4 obtained 5 with 5 with 7 strength 6 grip 7 strength 8 and 9 walking conclusions : both self [-] reports and objective measures capture information on the functional ability of older people that can be used to predict disability [onset] . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 7 and 2 : 24 predict 2 : 27 . 3 both 6 reports 4 self 6 reports 6 reports 7 and 7 and 9 measures 7 and 10 capture 8 objective 9 measures 10 capture 11 information 10 capture 12 on 12 on 15 ability 13 the 15 ability 14 functional 15 ability 15 ability 16 of 16 of 18 people 17 older 18 people 18 people 19 that 18 people 24 predict 19 that 20 can 20 can 21 be 21 be 22 used 22 used 23 to 22 used 24 predict 23 to 24 predict 24 predict 25 disability objective measures offer little to the development of intervention strategies , whereas self [-] reports provide some insight into the demands of the environment , being more amenable to interventions . 0 ###LEFT-WALL### 2 measures 0 ###LEFT-WALL### 3 offer 1 objective 2 measures 2 measures 3 offer 3 offer 4 little 3 offer 5 to 3 offer 12 whereas 3 offer 26 being 5 to 7 development 6 the 7 development 7 development 8 of 8 of 10 strategies 9 intervention 10 strategies 11 , 12 whereas 12 whereas 15 reports 12 whereas 16 provide 12 whereas 25 , 13 self 15 reports 15 reports 16 provide 16 provide 18 insight 16 provide 19 into 17 some 18 insight 19 into 21 demands 20 the 21 demands 21 demands 22 of 22 of 24 environment 23 the 24 environment 25 , 26 being 26 being 28 amenable 26 being 31 . 27 more 28 amenable 28 amenable 29 to 29 to 30 interventions the mechanical properties of skin are determined primarily by the extracellular matrix of the dermis . 0 ###LEFT-WALL### 3 properties 0 ###LEFT-WALL### 6 are 0 ###LEFT-WALL### 16 . 1 the 3 properties 2 mechanical 3 properties 3 properties 4 of 3 properties 6 are 4 of 5 skin 6 are 7 determined 7 determined 8 primarily 8 primarily 9 by 9 by 12 matrix 10 the 12 matrix 11 extracellular 12 matrix 12 matrix 13 of 13 of 15 dermis 14 the 15 dermis these mechanical and biological properties change significantly as a function of age . 0 ###LEFT-WALL### 5 properties 0 ###LEFT-WALL### 6 change 0 ###LEFT-WALL### 13 . 1 these 5 properties 2 mechanical 3 and 3 and 4 biological 3 and 5 properties 5 properties 6 change 6 change 7 significantly 6 change 8 as 8 as 10 function 9 a 10 function 10 function 11 of 11 of 12 age key components of the extracellular matrix are proteoglycans , which are molecules composed of a core protein and covalently attached glycosaminoglycans . 0 ###LEFT-WALL### 2 components 0 ###LEFT-WALL### 7 are 0 ###LEFT-WALL### 9 , 0 ###LEFT-WALL### 22 . 1 key 2 components 2 components 3 of 2 components 7 are 3 of 6 matrix 4 the 6 matrix 5 extracellular 6 matrix 7 are 8 proteoglycans 9 , 10 which 9 , 11 are 10 which 11 are 11 are 18 and 12 molecules 13 composed 12 molecules 14 of 12 molecules 18 and 14 of 17 protein 15 a 17 protein 16 core 17 protein 18 and 21 glycosaminoglycans 19 covalently 20 attached 20 attached 21 glycosaminoglycans proteoglycans and their constituent glycosaminoglycans are involved in many biological processes which are important for [dermal] function , such as proper formation of the collagen network . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 17 function 1 proteoglycans 2 and 2 and 4 constituent 2 and 5 glycosaminoglycans 2 and 15 for 2 and 17 function 3 their 4 constituent 5 glycosaminoglycans 6 are 6 are 7 involved 7 involved 8 in 7 involved 15 for 8 in 11 processes 9 many 11 processes 10 biological 11 processes 11 processes 12 which 11 processes 13 are 12 which 13 are 13 are 14 important 17 function 20 as 18 , 20 as 19 such 20 as 20 as 22 formation 20 as 27 . 21 proper 22 formation 22 formation 23 of 23 of 26 network 24 the 26 network 25 collagen 26 network a recently developed compound , c - xylopyranoside derivative [(] c - xyloside ) , was designed to mimic β - xylosides , which are known initiators of glycosaminoglycan biosynthesis . 0 ###LEFT-WALL### 4 compound 0 ###LEFT-WALL### 17 designed 1 a 4 compound 2 recently 3 developed 3 developed 4 compound 4 compound 7 - 4 compound 16 was 5 , 7 - 6 c 7 - 7 - 9 derivative 7 - 15 , 8 xylopyranoside 9 derivative 9 derivative 11 c 9 derivative 13 xyloside 12 - 13 xyloside 13 xyloside 14 ) 16 was 17 designed 17 designed 18 to 17 designed 19 mimic 18 to 19 mimic 19 mimic 22 xylosides 20 β 21 - 20 β 22 xylosides 22 xylosides 24 which 23 , 24 which 24 which 25 are 24 which 31 . 25 are 27 initiators 26 known 27 initiators 27 initiators 28 of 28 of 30 biosynthesis 29 glycosaminoglycan 30 biosynthesis c - xyloside was found , by several criteria , to act like β - xylosides , such as [in] the eliciting of an increase in glycosaminoglycan synthesis by human dermal fibroblasts in culture . 0 ###LEFT-WALL### 1 c 0 ###LEFT-WALL### 2 - 0 ###LEFT-WALL### 35 . 1 c 2 - 2 - 3 xyloside 3 xyloside 4 was 4 was 5 found 5 found 7 by 5 found 11 to 5 found 26 in 6 , 7 by 7 by 9 criteria 7 by 10 , 8 several 9 criteria 11 to 12 act 12 act 13 like 12 act 19 as 13 like 14 β 14 β 16 xylosides 15 - 16 xylosides 16 xylosides 17 , 18 such 19 as 19 as 22 eliciting 21 the 22 eliciting 22 eliciting 23 of 23 of 25 increase 24 an 25 increase 26 in 28 synthesis 27 glycosaminoglycan 28 synthesis 28 synthesis 29 by 29 by 32 fibroblasts 30 human 32 fibroblasts 31 dermal 32 fibroblasts 32 fibroblasts 33 in 33 in 34 culture this increase may lead to the preservation of matrix integrity and thereby contribute to the firmness of skin . 0 ###LEFT-WALL### 2 increase 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 19 . 1 this 2 increase 2 increase 3 may 3 may 11 and 4 lead 5 to 4 lead 11 and 5 to 7 preservation 6 the 7 preservation 7 preservation 8 of 8 of 10 integrity 9 matrix 10 integrity 11 and 13 contribute 12 thereby 13 contribute 13 contribute 14 to 14 to 16 firmness 15 the 16 firmness 16 firmness 17 of 17 of 18 skin thus , [c] [-] xyloside may be useful in improving the quality of skin . 0 ###LEFT-WALL### 5 xyloside 0 ###LEFT-WALL### 7 be 0 ###LEFT-WALL### 15 . 1 thus 2 , 1 thus 5 xyloside 5 xyloside 6 may 6 may 7 be 7 be 8 useful 8 useful 9 in 9 in 10 improving 10 improving 12 quality 11 the 12 quality 12 quality 13 of 13 of 14 skin we compared new york city suicide victims aged 18 - 59 with those 60+ according to rates by which psychotropic/analgesic drugs and ethanol contributed to death . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 compared 0 ###LEFT-WALL### 10 - 1 we 2 compared 2 compared 7 victims 3 new 4 york 4 york 7 victims 5 city 7 victims 6 suicide 7 victims 7 victims 8 aged 8 aged 9 18 10 - 11 59 10 - 14 60+ 10 - 27 . 11 59 12 with 11 59 14 60+ 12 with 13 those 14 60+ 16 to 14 60+ 25 to 15 according 16 to 16 to 17 rates 17 rates 18 by 18 by 19 which 18 by 22 and 18 by 24 contributed 20 psychotropic/analgesic 21 drugs 21 drugs 22 and 22 and 23 ethanol 22 and 24 contributed 25 to 26 death barbiturates were more frequent in the elderly , while antidepressants were more frequent in younger adults . 0 ###LEFT-WALL### 1 barbiturates 0 ###LEFT-WALL### 2 were 1 barbiturates 2 were 2 were 4 frequent 3 more 4 frequent 4 frequent 5 in 4 frequent 9 while 5 in 7 elderly 6 the 7 elderly 8 , 9 while 9 while 10 antidepressants 9 while 11 were 9 while 17 . 10 antidepressants 11 were 11 were 13 frequent 12 more 13 frequent 13 frequent 14 in 14 in 16 adults 15 younger 16 adults addressing the potential [for] overdose with barbiturates may aid suicide prevention in the elderly . 0 ###LEFT-WALL### 1 addressing 0 ###LEFT-WALL### 9 aid 0 ###LEFT-WALL### 15 . 1 addressing 5 overdose 1 addressing 6 with 1 addressing 8 may 2 the 5 overdose 3 potential 5 overdose 6 with 7 barbiturates 8 may 9 aid 9 aid 11 prevention 9 aid 12 in 10 suicide 11 prevention 12 in 14 elderly 13 the 14 elderly stem cells are uniquely able to [self] [-] renew [,] to undergo multilineage differentiation , and to persist throughout life in a number of tissues . 0 ###LEFT-WALL### 2 cells 0 ###LEFT-WALL### 16 and 0 ###LEFT-WALL### 26 . 1 stem 2 cells 2 cells 3 are 3 are 4 uniquely 3 are 5 able 5 able 6 to 6 to 16 and 9 renew 11 to 9 renew 14 differentiation 9 renew 16 and 11 to 12 undergo 12 undergo 13 multilineage 15 , 16 and 16 and 17 to 16 and 18 persist 17 to 18 persist 18 persist 19 throughout 18 persist 21 in 19 throughout 20 life 21 in 25 tissues 22 a 23 number 23 number 24 of 23 number 25 tissues 24 of 25 tissues stem cells are regulated by a combination of shared [and] tissue - specific mechanisms [and] are distinguished from restricted progenitors by differences in transcriptional and epigenetic regulation . 0 ###LEFT-WALL### 1 stem 0 ###LEFT-WALL### 9 shared 0 ###LEFT-WALL### 12 - 1 stem 2 cells 1 stem 8 of 1 stem 9 shared 2 cells 3 are 3 are 4 regulated 4 regulated 5 by 5 by 7 combination 6 a 7 combination 7 combination 8 of 9 shared 11 tissue 12 - 14 mechanisms 12 - 16 are 12 - 28 . 13 specific 14 mechanisms 14 mechanisms 16 are 16 are 17 distinguished 17 distinguished 18 from 17 distinguished 21 by 18 from 20 progenitors 19 restricted 20 progenitors 21 by 22 differences 22 differences 23 in 23 in 27 regulation 24 transcriptional 25 and 25 and 26 epigenetic 25 and 27 regulation emerging evidence suggests that other aspects of cellular physiology , including mitosis , signal transduction , and metabolic regulation , also differ between stem cells and their progeny . 0 ###LEFT-WALL### 2 evidence 0 ###LEFT-WALL### 3 suggests 0 ###LEFT-WALL### 29 . 1 emerging 2 evidence 2 evidence 3 suggests 3 suggests 4 that 4 that 6 aspects 4 that 20 , 5 other 6 aspects 6 aspects 7 of 6 aspects 20 , 7 of 9 physiology 8 cellular 9 physiology 9 physiology 11 including 10 , 11 including 11 including 12 mitosis 11 including 13 , 14 signal 17 and 14 signal 20 , 15 transduction 17 and 16 , 17 and 17 and 19 regulation 18 metabolic 19 regulation 20 , 22 differ 21 also 22 differ 22 differ 23 between 23 between 26 and 24 stem 25 cells 25 cells 26 and 26 and 28 progeny 27 their 28 progeny these differences may allow stem cells to be regulated independently of differentiated cells in response to circadian rhythms , changes in metabolism , diet , exercise , mating , aging , infection , and disease . 0 ###LEFT-WALL### 2 differences 0 ###LEFT-WALL### 23 , 0 ###LEFT-WALL### 25 , 0 ###LEFT-WALL### 36 . 1 these 2 differences 2 differences 23 , 3 may 19 , 3 may 23 , 4 allow 6 cells 4 allow 7 to 4 allow 9 regulated 4 allow 19 , 5 stem 6 cells 7 to 8 be 8 be 9 regulated 9 regulated 10 independently 9 regulated 16 to 10 independently 11 of 11 of 13 cells 12 differentiated 13 cells 14 in 15 response 15 response 16 to 16 to 18 rhythms 17 circadian 18 rhythms 19 , 20 changes 19 , 21 in 21 in 22 metabolism 23 , 24 diet 25 , 26 exercise 25 , 31 , 26 exercise 28 mating 27 , 28 mating 28 mating 30 aging 28 mating 31 , 29 , 30 aging 30 aging 31 , 31 , 34 and 32 infection 34 and 33 , 34 and 34 and 35 disease this allows stem cells to sustain homeostasis or to remodel relevant tissues in response to physiological change . 0 ###LEFT-WALL### 1 this 0 ###LEFT-WALL### 2 allows 0 ###LEFT-WALL### 18 . 1 this 2 allows 2 allows 4 cells 2 allows 5 to 2 allows 8 or 3 stem 4 cells 5 to 8 or 6 sustain 7 homeostasis 6 sustain 8 or 8 or 9 to 8 or 10 remodel 9 to 10 remodel 10 remodel 12 tissues 10 remodel 15 to 11 relevant 12 tissues 13 in 14 response 14 response 15 to 15 to 17 change 16 physiological 17 change stem cells are therefore not only regulated by short - range signals that maintain homeostasis within their tissue of origin , but also by long - range signals that integrate stem cell function [with] systemic physiology . 0 ###LEFT-WALL### 2 cells 0 ###LEFT-WALL### 7 regulated 0 ###LEFT-WALL### 37 . 1 stem 2 cells 2 cells 3 are 3 are 5 not 3 are 6 only 3 are 7 regulated 4 therefore 5 not 7 regulated 8 by 7 regulated 22 but 8 by 12 signals 9 short 10 - 9 short 11 range 11 range 12 signals 12 signals 13 that 12 signals 14 maintain 13 that 14 maintain 14 maintain 15 homeostasis 16 within 18 tissue 16 within 22 but 17 their 18 tissue 18 tissue 19 of 19 of 20 origin 21 , 22 but 22 but 23 also 22 but 24 by 24 by 28 signals 25 long 26 - 25 long 27 range 27 range 28 signals 28 signals 29 that 28 signals 30 integrate 29 that 30 integrate 30 integrate 36 physiology 31 stem 33 function 32 cell 33 function 33 function 36 physiology 35 systemic 36 physiology in vertebrates , skeletal muscle is derived from mesodermal structures called somites . 0 ###LEFT-WALL### 5 muscle 0 ###LEFT-WALL### 7 derived 0 ###LEFT-WALL### 13 . 1 in 2 vertebrates 1 in 3 , 1 in 5 muscle 4 skeletal 5 muscle 5 muscle 6 is 6 is 7 derived 7 derived 8 from 8 from 10 structures 9 mesodermal 10 structures 10 structures 11 called 11 called 12 somites myogenic progenitor cells that form skeletal muscles of the trunk and limbs are derived from the dermomyotome , the dorsal region of the somite . 0 ###LEFT-WALL### 3 cells 0 ###LEFT-WALL### 14 derived 1 myogenic 3 cells 2 progenitor 3 cells 3 cells 4 that 3 cells 5 form 3 cells 13 are 4 that 5 form 5 form 7 muscles 6 skeletal 7 muscles 7 muscles 8 of 8 of 11 and 9 the 10 trunk 10 trunk 11 and 11 and 12 limbs 13 are 14 derived 14 derived 15 from 15 from 17 dermomyotome 16 the 17 dermomyotome 17 dermomyotome 21 region 18 , 21 region 19 the 21 region 20 dorsal 21 region 21 region 22 of 21 region 25 . 22 of 24 somite 23 the 24 somite these cells enter the myogenic program by activating a set of four myogenic regulatory factors . 0 ###LEFT-WALL### 2 cells 0 ###LEFT-WALL### 3 enter 0 ###LEFT-WALL### 16 . 1 these 2 cells 2 cells 3 enter 3 enter 6 program 3 enter 7 by 4 the 6 program 5 myogenic 6 program 7 by 8 activating 8 activating 10 set 9 a 10 set 10 set 11 of 11 of 15 factors 12 four 15 factors 13 myogenic 15 factors 14 regulatory 15 factors during embryonic and fetal growth , muscle progenitor cells provide the source for muscle growth . 0 ###LEFT-WALL### 9 cells 0 ###LEFT-WALL### 10 provide 0 ###LEFT-WALL### 16 . 1 during 5 growth 1 during 6 , 1 during 9 cells 2 embryonic 3 and 3 and 4 fetal 3 and 5 growth 7 muscle 9 cells 8 progenitor 9 cells 9 cells 10 provide 10 provide 12 source 11 the 12 source 12 source 13 for 13 for 15 growth 14 muscle 15 growth around birth , the muscle progenitor enters quiescence , and adopts a satellite cell position on muscle fibers , providing a pool of adult muscle stem cells . 0 ###LEFT-WALL### 6 progenitor 0 ###LEFT-WALL### 10 and 1 around 2 birth 1 around 3 , 1 around 6 progenitor 4 the 6 progenitor 5 muscle 6 progenitor 6 progenitor 10 and 7 enters 8 quiescence 7 enters 10 and 9 , 10 and 10 and 11 adopts 10 and 16 on 11 adopts 15 position 12 a 15 position 13 satellite 15 position 14 cell 15 position 16 on 18 fibers 17 muscle 18 fibers 18 fibers 20 providing 19 , 20 providing 20 providing 22 pool 20 providing 28 . 21 a 22 pool 22 pool 23 of 23 of 27 cells 24 adult 27 cells 25 muscle 27 cells 26 stem 27 cells they are essential for the growth and regeneration of muscles . 0 ###LEFT-WALL### 1 they 0 ###LEFT-WALL### 2 are 0 ###LEFT-WALL### 11 . 1 they 2 are 2 are 3 essential 3 essential 4 for 4 for 7 and 5 the 6 growth 6 growth 7 and 7 and 8 regeneration 7 and 9 of 9 of 10 muscles among the mechanisms that control the maintenance of satellite cells properties , the notch pathway plays a crucial role . 0 ###LEFT-WALL### 15 pathway 0 ###LEFT-WALL### 16 plays 0 ###LEFT-WALL### 20 . 1 among 3 mechanisms 1 among 12 , 1 among 15 pathway 2 the 3 mechanisms 3 mechanisms 4 that 3 mechanisms 5 control 4 that 5 control 5 control 7 maintenance 6 the 7 maintenance 7 maintenance 8 of 8 of 11 properties 9 satellite 11 properties 10 cells 11 properties 13 the 15 pathway 14 notch 15 pathway 15 pathway 16 plays 16 plays 19 role 17 a 18 crucial 17 a 19 role 18 crucial 19 role in facts , this pathway is implicated from the early steps of somitogenesis and the development of skeletal muscles in the embryo . 0 ###LEFT-WALL### 5 pathway 0 ###LEFT-WALL### 7 implicated 0 ###LEFT-WALL### 23 . 1 in 2 facts 1 in 3 , 1 in 5 pathway 4 this 5 pathway 5 pathway 6 is 6 is 7 implicated 7 implicated 8 from 7 implicated 20 in 8 from 11 steps 9 the 11 steps 10 early 11 steps 11 steps 12 of 12 of 14 and 13 somitogenesis 14 and 14 and 16 development 14 and 17 of 15 the 16 development 17 of 19 muscles 18 skeletal 19 muscles 20 in 22 embryo 21 the 22 embryo furthermore , during ageing , notch activity decreases which results [in] decreased muscle regeneration . 0 ###LEFT-WALL### 8 decreases 0 ###LEFT-WALL### 13 muscle 0 ###LEFT-WALL### 15 . 1 furthermore 2 , 1 furthermore 8 decreases 2 , 3 during 3 during 4 ageing 3 during 5 , 3 during 8 decreases 6 notch 8 decreases 7 activity 8 decreases 8 decreases 9 which 8 decreases 12 decreased 8 decreases 13 muscle 9 which 10 results 9 which 12 decreased 10 results 12 decreased 13 muscle 14 regeneration thus , the notch pathway is a key regulator of muscle plasticity . 0 ###LEFT-WALL### 5 pathway 0 ###LEFT-WALL### 6 is 0 ###LEFT-WALL### 13 . 1 thus 2 , 1 thus 5 pathway 3 the 5 pathway 4 notch 5 pathway 5 pathway 6 is 6 is 9 regulator 7 a 9 regulator 8 key 9 regulator 9 regulator 10 of 10 of 12 plasticity 11 muscle 12 plasticity objective : to evaluate causes and clinical management of postoperative pain after total knee arthroplasty ( tka ) . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 19 . 2 : 3 to 2 : 4 evaluate 3 to 4 evaluate 4 evaluate 6 and 4 evaluate 12 after 5 causes 6 and 6 and 8 management 6 and 9 of 7 clinical 8 management 9 of 11 pain 10 postoperative 11 pain 12 after 15 arthroplasty 13 total 14 knee 14 knee 15 arthroplasty 15 arthroplasty 17 tka 16 ( 17 tka 17 tka 18 ) methods : from january 2004 to june [2009] , 41 patients ( 44 knees ) with knee pain post tka were treated . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 23 . 2 : 5 2004 2 : 22 treated 3 from 4 january 3 from 5 2004 5 2004 6 to 5 2004 16 with 5 2004 21 were 6 to 7 june 7 june 11 patients 9 , 11 patients 10 41 11 patients 11 patients 14 knees 11 patients 15 ) 12 ( 14 knees 13 44 14 knees 14 knees 15 ) 16 with 20 tka 17 knee 18 pain 18 pain 20 tka 19 post 20 tka 21 were 22 treated there were 9 male and 32 female patients aging from 51 to 84 years with a mean of 63.5 years . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 were 0 ###LEFT-WALL### 21 . 1 there 2 were 2 were 5 and 3 9 5 and 4 male 5 and 5 and 8 patients 5 and 9 aging 6 32 8 patients 7 female 8 patients 9 aging 14 years 10 from 12 to 11 51 12 to 12 to 13 84 12 to 14 years 14 years 15 with 15 with 17 mean 16 a 17 mean 17 mean 18 of 18 of 20 years 19 63.5 20 years the diagnosis followed [to] brown diagnostic system . 0 ###LEFT-WALL### 7 system 0 ###LEFT-WALL### 8 . 1 the 7 system 2 diagnosis 3 followed 3 followed 7 system 5 brown 7 system 6 diagnostic 7 system one case of extraarticular pain was complex regional pain syndrome type 1 ( crps - 1 ) and underwent conservative treatment , the remaining 5 cases were treated by surgery . 0 ###LEFT-WALL### 2 case 0 ###LEFT-WALL### 18 and 0 ###LEFT-WALL### 22 , 0 ###LEFT-WALL### 31 . 1 one 2 case 2 case 3 of 2 case 6 was 3 of 5 pain 4 extraarticular 5 pain 6 was 18 and 7 complex 11 type 7 complex 18 and 8 regional 9 pain 9 pain 11 type 10 syndrome 11 type 11 type 12 1 11 type 14 crps 11 type 16 1 13 ( 14 crps 14 crps 15 - 15 - 16 1 16 1 17 ) 18 and 19 underwent 18 and 21 treatment 20 conservative 21 treatment 22 , 26 cases 22 , 28 treated 23 the 24 remaining 23 the 25 5 25 5 26 cases 26 cases 27 were 27 were 28 treated 28 treated 29 by 29 by 30 surgery three cases [of] joint instability , 1 case of patellar baja , 2 cases of soft tissue impingement caused [by] overhang of the prosthesis , 1 case of popliteal tendon impact underwent conservative treatment , the other 27 cases underwent surgical intervention . 0 ###LEFT-WALL### 2 cases 0 ###LEFT-WALL### 4 joint 0 ###LEFT-WALL### 25 , 0 ###LEFT-WALL### 43 . 1 three 2 cases 2 cases 4 joint 4 joint 5 instability 5 instability 8 case 5 instability 13 2 6 , 8 case 7 1 8 case 8 case 9 of 8 case 12 , 9 of 11 baja 10 patellar 11 baja 12 , 13 2 13 2 14 cases 13 2 21 overhang 13 2 22 of 13 2 25 , 14 cases 15 of 14 cases 21 overhang 15 of 18 impingement 16 soft 17 tissue 17 tissue 18 impingement 18 impingement 19 caused 22 of 24 prosthesis 23 the 24 prosthesis 25 , 27 case 25 , 32 underwent 25 , 35 , 26 1 27 case 27 case 28 of 27 case 32 underwent 28 of 31 impact 29 popliteal 30 tendon 30 tendon 31 impact 32 underwent 34 treatment 33 conservative 34 treatment 35 , 39 cases 35 , 40 underwent 36 the 37 other 37 other 38 27 38 27 39 cases 39 cases 40 underwent 40 underwent 42 intervention 41 surgical 42 intervention the patients were followed up and the knee society score ( kss ) knee score [,] pain visual analog scale ( vas ) [score] were recorded . 0 ###LEFT-WALL### 2 patients 0 ###LEFT-WALL### 4 followed 0 ###LEFT-WALL### 6 and 0 ###LEFT-WALL### 27 . 1 the 2 patients 2 patients 3 were 3 were 4 followed 4 followed 5 up 6 and 20 scale 6 and 26 recorded 7 the 20 scale 8 knee 9 society 9 society 10 score 10 score 12 kss 11 ( 12 kss 12 kss 13 ) 12 kss 20 scale 14 knee 17 pain 15 score 17 pain 17 pain 20 scale 18 visual 19 analog 19 analog 20 scale 20 scale 22 vas 20 scale 25 were 21 ( 22 vas 22 vas 23 ) 25 were 26 recorded results : forty - one cases were followed up for 1 to 6 years . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 15 . 2 : 3 forty 2 : 8 followed 3 forty 5 one 3 forty 6 cases 3 forty 7 were 4 - 5 one 5 one 6 cases 7 were 8 followed 8 followed 9 up 8 followed 10 for 10 for 14 years 11 1 12 to 12 to 13 6 12 to 14 years at the last time of [follow] - up , the 5 cases received surgical treatment to extra - articular pain showed vas score as 2.5 ± 0.2 , kss clinical and functional score as 92.8 ± 2.6 and 89.0 ± 3.4 . 0 ###LEFT-WALL### 23 score 0 ###LEFT-WALL### 42 . 1 at 4 time 1 at 23 score 2 the 4 time 3 last 4 time 4 time 15 treatment 4 time 21 showed 5 of 8 up 5 of 9 , 5 of 15 treatment 7 - 8 up 10 the 15 treatment 11 5 12 cases 12 cases 13 received 13 received 15 treatment 14 surgical 15 treatment 15 treatment 16 to 15 treatment 21 showed 16 to 20 pain 17 extra 18 - 17 extra 20 pain 19 articular 20 pain 21 showed 22 vas 23 score 24 as 24 as 38 and 25 2.5 26 ± 26 ± 27 0.2 26 ± 28 , 28 , 36 ± 28 , 38 and 29 kss 36 ± 30 clinical 31 and 31 and 33 score 31 and 34 as 31 and 36 ± 32 functional 33 score 34 as 35 92.8 36 ± 37 2.6 38 and 40 ± 39 89.0 40 ± 40 ± 41 3.4 there [was] [significantly] difference compared [with] preoperative ( p < 0.05 ) . 0 ###LEFT-WALL### 4 difference 0 ###LEFT-WALL### 5 compared 0 ###LEFT-WALL### 13 . 1 there 4 difference 4 difference 5 compared 5 compared 7 preoperative 7 preoperative 10 < 8 ( 10 < 9 p 10 < 10 < 11 0.05 10 < 12 ) one case of crps [-] 1 performed conservative treatment , the therapy was effective . 0 ###LEFT-WALL### 2 case 0 ###LEFT-WALL### 7 performed 0 ###LEFT-WALL### 10 , 0 ###LEFT-WALL### 15 . 1 one 2 case 2 case 3 of 2 case 7 performed 3 of 4 crps 4 crps 6 1 7 performed 9 treatment 8 conservative 9 treatment 10 , 12 therapy 10 , 13 was 11 the 12 therapy 12 therapy 13 was 13 was 14 effective in the infected 12 cases of [intra] [-] articular pain , 1 case received amputation , 3 cases received antibiotic bone cement insert , 8 cases received two stage revision . 0 ###LEFT-WALL### 12 1 0 ###LEFT-WALL### 16 , 0 ###LEFT-WALL### 31 . 1 in 5 cases 1 in 11 , 1 in 12 1 2 the 5 cases 3 infected 5 cases 4 12 5 cases 5 cases 6 of 6 of 10 pain 9 articular 10 pain 12 1 13 case 13 case 15 amputation 14 received 15 amputation 16 , 23 insert 16 , 24 , 17 3 19 received 18 cases 19 received 19 received 23 insert 20 antibiotic 23 insert 21 bone 23 insert 22 cement 23 insert 24 , 26 cases 24 , 27 received 25 8 26 cases 26 cases 27 received 27 received 30 revision 28 two 29 stage 29 stage 30 revision all infections were cured , and vas [score] was 3.8 ± 0.2 , kss clinical score [was] 88.3 ± [4.6] , function [score] was 85.0 ± 4.6 postoperatively , with [significantly] difference compared [with] preoperative ( p < 0.05 ) . 0 ###LEFT-WALL### 2 infections 0 ###LEFT-WALL### 3 were 0 ###LEFT-WALL### 5 , 1 all 2 infections 2 infections 3 were 3 were 4 cured 5 , 6 and 5 , 9 was 5 , 13 , 6 and 7 vas 7 vas 9 was 9 was 11 ± 10 3.8 11 ± 11 ± 12 0.2 13 , 22 function 14 kss 22 function 15 clinical 16 score 16 score 22 function 18 88.3 22 function 19 ± 21 , 19 ± 22 function 22 function 24 was 24 was 26 ± 24 was 28 postoperatively 24 was 30 with 25 85.0 26 ± 26 ± 27 4.6 29 , 30 with 30 with 32 difference 30 with 33 compared 30 with 41 . 33 compared 35 preoperative 35 preoperative 38 < 36 ( 38 < 37 p 38 < 38 < 39 0.05 38 < 40 ) in the 8 cases received conservative treatment [in] [non] - infected group , at the last time [of] follow - up , vas score [was] 4.5 ± 0.4 , kss clinical and functional score was 85.4 ± 4.2 and 84.2 ± 2.3 , with [significantly] difference compared [with] preoperative ( p < 0.05 ) . 0 ###LEFT-WALL### 4 cases 0 ###LEFT-WALL### 5 received 0 ###LEFT-WALL### 10 - 1 in 3 8 1 in 4 cases 2 the 3 8 4 cases 5 received 5 received 7 treatment 6 conservative 7 treatment 10 - 12 group 10 - 13 , 10 - 22 , 11 infected 12 group 13 , 19 follow 13 , 20 - 14 at 17 time 14 at 19 follow 15 the 16 last 15 the 17 time 20 - 21 up 22 , 23 vas 22 , 29 , 23 vas 24 score 24 score 27 ± 26 4.5 27 ± 27 ± 28 0.4 29 , 30 kss 29 , 35 was 29 , 39 and 30 kss 32 and 30 kss 34 score 30 kss 35 was 31 clinical 32 and 32 and 33 functional 32 and 34 score 35 was 37 ± 36 85.4 37 ± 37 ± 38 4.2 39 and 40 84.2 39 and 41 ± 40 84.2 41 ± 41 ± 42 2.3 41 ± 44 with 43 , 44 with 44 with 46 difference 44 with 47 compared 44 with 55 . 47 compared 49 preoperative 49 preoperative 52 < 50 ( 52 < 51 p 52 < 52 < 53 0.05 52 < 54 ) fifteen cases underwent surgical treatment , at the last time [of] follow - up , vas score [was] 3.4 ± 0.1 , kss clinical and functional score was 86.6 ± 5.4 and 87.1 ± 2.4 , with [significantly] difference compared [with] preoperative ( p < 0.05 ) . 0 ###LEFT-WALL### 2 cases 0 ###LEFT-WALL### 3 underwent 0 ###LEFT-WALL### 6 , 1 fifteen 2 cases 2 cases 3 underwent 3 underwent 5 treatment 4 surgical 5 treatment 6 , 12 follow 6 , 15 , 7 at 10 time 7 at 12 follow 8 the 9 last 8 the 10 time 12 follow 14 up 13 - 14 up 14 up 15 , 15 , 17 score 15 , 22 , 16 vas 17 score 17 score 20 ± 19 3.4 20 ± 20 ± 21 0.1 22 , 23 kss 22 , 28 was 23 kss 25 and 23 kss 27 score 23 kss 28 was 24 clinical 25 and 25 and 26 functional 25 and 27 score 28 was 32 and 29 86.6 30 ± 30 ± 31 5.4 30 ± 32 and 32 and 34 ± 32 and 37 with 33 87.1 34 ± 34 ± 35 2.4 36 , 37 with 37 with 39 difference 37 with 42 preoperative 37 with 48 . 39 difference 40 compared 42 preoperative 45 < 43 ( 45 < 44 p 45 < 45 < 46 0.05 45 < 47 ) conclusions : patients with knee pain post tka need systematic assessment to identify the causes . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 3 patients 2 : 9 need 2 : 16 . 3 patients 4 with 3 patients 9 need 4 with 8 tka 5 knee 8 tka 6 pain 8 tka 7 post 8 tka 9 need 11 assessment 9 need 12 to 9 need 13 identify 10 systematic 11 assessment 12 to 13 identify 13 identify 15 causes 14 the 15 causes appropriate treatment due to the positive diagnosis generally [lead] to satisfactory results , surgical intervention with indefinite causes is strictly prohibited . 0 ###LEFT-WALL### 1 appropriate 0 ###LEFT-WALL### 13 , 0 ###LEFT-WALL### 22 . 1 appropriate 2 treatment 1 appropriate 4 to 1 appropriate 8 generally 1 appropriate 10 to 3 due 4 to 4 to 7 diagnosis 5 the 7 diagnosis 6 positive 7 diagnosis 10 to 12 results 11 satisfactory 12 results 13 , 15 intervention 13 , 21 prohibited 14 surgical 15 intervention 15 intervention 16 with 15 intervention 19 is 16 with 18 causes 17 indefinite 18 causes 19 is 21 prohibited 20 strictly 21 prohibited objective : to investigate the correlation of endogenous androgen and androgen receptor ( ar ) level with coronary artery diseases ( cad ) in elderly males and elucidate the potential mechanism of gender [difference] in the prevalence of cad . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 2 : 27 and 2 : 40 . 3 to 4 investigate 3 to 15 ) 3 to 27 and 4 investigate 6 correlation 5 the 6 correlation 6 correlation 7 of 7 of 10 and 8 endogenous 9 androgen 9 androgen 10 and 10 and 12 receptor 10 and 14 ar 11 androgen 12 receptor 13 ( 14 ar 14 ar 15 ) 16 level 17 with 16 level 27 and 17 with 20 diseases 17 with 24 in 18 coronary 20 diseases 19 artery 20 diseases 20 diseases 22 cad 21 ( 22 cad 22 cad 23 ) 24 in 26 males 25 elderly 26 males 27 and 28 elucidate 28 elucidate 31 mechanism 28 elucidate 35 in 29 the 31 mechanism 30 potential 31 mechanism 31 mechanism 32 of 32 of 33 gender 35 in 37 prevalence 36 the 37 prevalence 37 prevalence 38 of 38 of 39 cad methods : a total of 296 male patients from different centers were divided into the cad group ( n = 237 ) and the control group ( n = 59 ) according to the results of coronary angiography . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 23 and 2 : 26 group 2 : 39 . 3 a 4 total 4 total 5 of 4 total 13 divided 4 total 23 and 5 of 6 296 6 296 8 patients 6 296 12 were 7 male 8 patients 8 patients 9 from 8 patients 12 were 9 from 11 centers 10 different 11 centers 13 divided 14 into 13 divided 20 = 14 into 17 group 15 the 17 group 16 cad 17 group 18 ( 20 = 19 n 20 = 20 = 21 237 20 = 22 ) 23 and 25 control 23 and 26 group 24 the 25 control 26 group 29 = 26 group 33 to 27 ( 29 = 28 n 29 = 29 = 30 59 29 = 31 ) 32 according 33 to 33 to 35 results 34 the 35 results 35 results 36 of 36 of 38 angiography 37 coronary 38 angiography their mean ages were 68.6 ± 6.8 and 66.2 ± 6.5 years old respectively . 0 ###LEFT-WALL### 3 ages 0 ###LEFT-WALL### 4 were 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 15 . 1 their 3 ages 2 mean 3 ages 3 ages 4 were 4 were 6 ± 5 68.6 6 ± 6 ± 7 6.8 8 and 9 66.2 8 and 10 ± 9 66.2 10 ± 10 ± 11 6.5 10 ± 14 respectively 11 6.5 13 old 12 years 13 old the serum levels of ft ( free testosterone ) , tt ( total testosterone ) , e2 ( estradiol ) , lh ( luteinizing [hormone] ) , fsh ( follicle - stimulating hormone [ )(, shbg ( sex hormone [-] binding globulin ) and dhea ( dehydroepiandrosterone ) were measured in all participants . 0 ###LEFT-WALL### 44 and 0 ###LEFT-WALL### 49 were 0 ###LEFT-WALL### 54 . 1 the 3 levels 2 serum 3 levels 3 levels 4 of 3 levels 10 , 4 of 5 ft 5 ft 8 testosterone 6 ( 8 testosterone 7 free 8 testosterone 8 testosterone 9 ) 10 , 11 tt 10 , 16 , 11 tt 14 testosterone 12 ( 14 testosterone 13 total 14 testosterone 14 testosterone 15 ) 16 , 17 e2 16 , 21 , 17 e2 19 estradiol 18 ( 19 estradiol 19 estradiol 20 ) 21 , 33 hormone 21 , 35 )(, 22 lh 24 luteinizing 22 lh 28 fsh 22 lh 33 hormone 23 ( 24 luteinizing 24 luteinizing 26 ) 27 , 28 fsh 28 fsh 30 follicle 28 fsh 31 - 29 ( 30 follicle 30 follicle 31 - 32 stimulating 33 hormone 35 )(, 36 shbg 35 )(, 44 and 36 shbg 42 globulin 37 ( 42 globulin 38 sex 41 binding 39 hormone 41 binding 41 binding 42 globulin 42 globulin 43 ) 44 and 45 dhea 44 and 49 were 45 dhea 47 dehydroepiandrosterone 46 ( 47 dehydroepiandrosterone 47 dehydroepiandrosterone 48 ) 49 were 50 measured 50 measured 51 in 51 in 53 participants 52 all 53 participants and the androgen receptors of peripheral lymphocytes were assessed by flow cytometry . 0 ###LEFT-WALL### 1 and 0 ###LEFT-WALL### 13 . 1 and 4 receptors 1 and 9 assessed 2 the 4 receptors 3 androgen 4 receptors 4 receptors 5 of 4 receptors 8 were 5 of 7 lymphocytes 6 peripheral 7 lymphocytes 8 were 9 assessed 9 assessed 10 by 10 by 12 cytometry 11 flow 12 cytometry results : the serum level of ft was lower in the cad group than [that] [in] the control group [[] ( 24.1 ± 22.2 ) × 10 ( - 9 ) [mmol/l] [vs] ( 34.1 ± 31.8 [ )(× 10 ( - 9 ) [mmol/l] , p = 0.06 ] . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 4 serum 2 : 14 than 3 the 4 serum 5 level 6 of 5 level 8 was 6 of 7 ft 8 was 9 lower 9 lower 10 in 9 lower 14 than 10 in 13 group 11 the 13 group 12 cad 13 group 14 than 19 group 14 than 26 × 17 the 19 group 18 control 19 group 19 group 23 ± 19 group 26 × 21 ( 23 ± 22 24.1 23 ± 23 ± 24 22.2 23 ± 25 ) 26 × 27 10 27 10 30 9 27 10 39 )(× 28 ( 30 9 29 - 30 9 30 9 31 ) 34 ( 39 )(× 35 34.1 39 )(× 36 ± 39 )(× 37 31.8 39 )(× 39 )(× 48 = 39 )(× 51 . 40 10 42 - 41 ( 42 - 42 - 43 9 42 - 44 ) 42 - 48 = 46 , 48 = 47 p 48 = 48 = 49 0.06 48 = 50 ] but two groups showed no statistic differences in the levels of tt [,] e ( 2 ) , lh , fsh , shbg , dhea and lymphocyte ar ( 56.3 % ± 24.00 vs 57.1 % ± 20.8 [%] ) . 0 ###LEFT-WALL### 1 but 0 ###LEFT-WALL### 22 , 0 ###LEFT-WALL### 41 . 1 but 3 groups 1 but 4 showed 2 two 3 groups 3 groups 4 showed 4 showed 6 statistic 4 showed 7 differences 5 no 6 statistic 7 differences 8 in 7 differences 11 of 7 differences 21 fsh 8 in 10 levels 9 the 10 levels 11 of 12 tt 12 tt 14 e 12 tt 16 2 15 ( 16 2 16 2 17 ) 18 , 21 fsh 19 lh 21 fsh 20 , 21 fsh 21 fsh 22 , 22 , 26 and 23 shbg 24 , 24 , 25 dhea 24 , 26 and 26 and 28 ar 26 and 32 ± 27 lymphocyte 28 ar 29 ( 32 ± 30 56.3 31 % 31 % 32 ± 32 ± 33 24.00 32 ± 34 vs 32 ± 40 ) 34 vs 37 ± 35 57.1 36 % 36 % 37 ± 37 ± 38 20.8 as demonstrated by the logistic regression analysis , the level of ft was negatively correlated with the cad risk ( [or] = 0.98 , p = 0.0049 ) and positively correlated with the peripheral lymphocyte ar level . 0 ###LEFT-WALL### 10 level 0 ###LEFT-WALL### 29 and 0 ###LEFT-WALL### 38 . 1 as 2 demonstrated 1 as 10 level 3 by 7 analysis 3 by 8 , 3 by 10 level 4 the 7 analysis 5 logistic 6 regression 6 regression 7 analysis 9 the 10 level 10 level 11 of 10 level 29 and 11 of 12 ft 13 was 15 correlated 13 was 29 and 14 negatively 15 correlated 15 correlated 16 with 15 correlated 26 = 16 with 19 risk 17 the 19 risk 18 cad 19 risk 19 risk 23 0.98 20 ( 23 0.98 22 = 23 0.98 23 0.98 24 , 25 p 26 = 26 = 27 0.0049 26 = 28 ) 29 and 31 correlated 29 and 32 with 30 positively 31 correlated 32 with 37 level 33 the 37 level 34 peripheral 35 lymphocyte 35 lymphocyte 37 level 36 ar 37 level however age was negatively correlated with the levels of ft and ar . 0 ###LEFT-WALL### 2 age 0 ###LEFT-WALL### 5 correlated 0 ###LEFT-WALL### 13 . 1 however 2 age 2 age 3 was 3 was 4 negatively 3 was 5 correlated 5 correlated 6 with 6 with 8 levels 7 the 8 levels 8 levels 9 of 9 of 11 and 10 ft 11 and 11 and 12 ar conclusion : the deficiency of endogenous androgen contributes to a high prevalence of cad in elderly males . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 4 deficiency 2 : 8 contributes 2 : 18 . 3 the 4 deficiency 4 deficiency 5 of 4 deficiency 8 contributes 5 of 7 androgen 6 endogenous 7 androgen 8 contributes 9 to 8 contributes 15 in 9 to 12 prevalence 10 a 12 prevalence 11 high 12 prevalence 12 prevalence 13 of 13 of 14 cad 15 in 17 males 16 elderly 17 males the age - related decreases of ft and ar impair the physiological functions of androgen so as to accelerate the progression of coronary atherosclerosis . 0 ###LEFT-WALL### 2 age 0 ###LEFT-WALL### 3 - 1 the 2 age 3 - 5 decreases 3 - 10 impair 3 - 25 . 4 related 5 decreases 5 decreases 6 of 5 decreases 10 impair 6 of 8 and 7 ft 8 and 8 and 9 ar 10 impair 13 functions 10 impair 18 to 11 the 13 functions 12 physiological 13 functions 13 functions 14 of 14 of 15 androgen 16 so 17 as 17 as 18 to 18 to 19 accelerate 19 accelerate 21 progression 20 the 21 progression 21 progression 22 of 22 of 24 atherosclerosis 23 coronary 24 atherosclerosis background : age - related gene expression patterns of homo sapiens as well as of model organisms such as mus musculus , saccharomyces cerevisiae , caenorhabditis elegans and drosophila melanogaster are a basis for understanding the genetic mechanisms of ageing . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 3 age 0 ###LEFT-WALL### 5 related 1 background 2 : 2 : 3 age 4 - 5 related 5 related 8 patterns 5 related 12 as 5 related 14 as 5 related 41 . 6 gene 8 patterns 7 expression 8 patterns 8 patterns 9 of 9 of 11 sapiens 10 homo 11 sapiens 12 as 13 well 14 as 15 of 15 of 17 organisms 16 model 17 organisms 17 organisms 19 as 18 such 19 as 19 as 20 mus 20 mus 28 and 20 mus 35 understanding 21 musculus 22 , 22 , 24 cerevisiae 22 , 25 , 23 saccharomyces 24 cerevisiae 25 , 27 elegans 25 , 28 and 26 caenorhabditis 27 elegans 28 and 30 melanogaster 28 and 31 are 29 drosophila 30 melanogaster 31 are 33 basis 32 a 33 basis 33 basis 34 for 34 for 35 understanding 35 understanding 38 mechanisms 36 the 38 mechanisms 37 genetic 38 mechanisms 38 mechanisms 39 of 39 of 40 ageing for an effective analysis and interpretation of expression profiles it [is] necessary to store and manage huge amounts of data in an organized way , so that these data can be accessed and processed easily . 0 ###LEFT-WALL### 15 and 1 for 5 and 1 for 15 and 2 an 3 effective 2 an 4 analysis 3 effective 4 analysis 4 analysis 5 and 5 and 6 interpretation 5 and 7 of 7 of 8 expression 9 profiles 10 it 9 profiles 15 and 10 it 12 necessary 12 necessary 13 to 12 necessary 14 store 13 to 14 store 15 and 16 manage 16 manage 20 data 16 manage 21 in 16 manage 27 that 17 huge 18 amounts 18 amounts 19 of 18 amounts 20 data 19 of 20 data 21 in 24 way 22 an 23 organized 22 an 24 way 23 organized 24 way 25 , 27 that 26 so 27 that 27 that 29 data 27 that 31 be 27 that 36 . 28 these 29 data 29 data 30 can 30 can 31 be 31 be 33 and 32 accessed 33 and 33 and 34 processed 33 and 35 easily description : gisao.db ( genes involved in senescence , apoptosis and oxidative stress database ) is a web [-] based database system for storing and retrieving ageing - related experimental data . 0 ###LEFT-WALL### 1 description 0 ###LEFT-WALL### 2 : 2 : 3 gisao.db 2 : 16 is 3 gisao.db 11 and 3 gisao.db 16 is 4 ( 11 and 5 genes 6 involved 5 genes 9 , 6 involved 7 in 7 in 8 senescence 9 , 10 apoptosis 9 , 11 and 11 and 14 database 11 and 15 ) 12 oxidative 13 stress 13 stress 14 database 16 is 22 system 16 is 23 for 17 a 22 system 18 web 20 based 20 based 22 system 21 database 22 system 23 for 25 and 24 storing 25 and 25 and 27 ageing 25 and 31 data 26 retrieving 27 ageing 28 - 31 data 29 related 31 data 30 experimental 31 data 31 data 32 . expression data of genes and mirnas , annotation data like gene identifiers and go terms , orthologs data and data of follow - up experiments are stored in the database . 0 ###LEFT-WALL### 5 and 0 ###LEFT-WALL### 22 follow 0 ###LEFT-WALL### 23 - 1 expression 2 data 2 data 3 of 2 data 5 and 3 of 4 genes 5 and 6 mirnas 5 and 7 , 5 and 9 data 5 and 21 of 5 and 22 follow 8 annotation 9 data 9 data 10 like 9 data 16 , 10 like 13 and 11 gene 12 identifiers 12 identifiers 13 and 13 and 14 go 15 terms 16 , 16 , 17 orthologs 16 , 19 and 18 data 19 and 19 and 20 data 19 and 21 of 23 - 25 experiments 23 - 27 stored 23 - 31 . 24 up 25 experiments 25 experiments 26 are 26 are 27 stored 27 stored 28 in 28 in 30 database 29 the 30 database a user - friendly web application provides access to the stored data . 0 ###LEFT-WALL### 2 user 0 ###LEFT-WALL### 3 - 1 a 2 user 3 - 6 application 3 - 7 provides 3 - 13 . 4 friendly 5 web 5 web 6 application 6 application 7 provides 7 provides 8 access 7 provides 9 to 9 to 12 data 10 the 12 data 11 stored 12 data kegg pathways were incorporated and links to external databases augment the information in gisao.db . 0 ###LEFT-WALL### 2 pathways 0 ###LEFT-WALL### 10 augment 0 ###LEFT-WALL### 15 . 1 kegg 2 pathways 2 pathways 5 and 2 pathways 10 augment 3 were 4 incorporated 3 were 5 and 5 and 6 links 5 and 7 to 7 to 9 databases 8 external 9 databases 10 augment 12 information 10 augment 13 in 11 the 12 information 13 in 14 gisao.db search functions facilitate retrieval of data which can also be exported for further processing . 0 ###LEFT-WALL### 2 functions 0 ###LEFT-WALL### 3 facilitate 0 ###LEFT-WALL### 15 . 1 search 2 functions 2 functions 3 facilitate 3 facilitate 4 retrieval 4 retrieval 5 of 5 of 6 data 6 data 7 which 6 data 8 can 7 which 8 can 8 can 10 be 9 also 10 be 10 be 11 exported 11 exported 12 for 12 for 14 processing 13 further 14 processing conclusions : we have developed a centralized database that is very well suited for the management of data for ageing research . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 3 we 2 : 5 developed 2 : 22 . 3 we 4 have 4 have 5 developed 5 developed 8 database 6 a 8 database 7 centralized 8 database 8 database 9 that 8 database 10 is 9 that 10 is 10 is 12 well 10 is 13 suited 11 very 12 well 13 suited 14 for 14 for 16 management 15 the 16 management 16 management 17 of 17 of 18 data 18 data 19 for 19 for 21 research 20 ageing 21 research the database can be accessed at https://gisao.genome.tugraz.at and all the stored data can be viewed with a guest account . 0 ###LEFT-WALL### 2 database 0 ###LEFT-WALL### 5 accessed 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 20 . 1 the 2 database 2 database 3 can 3 can 4 be 4 be 5 accessed 5 accessed 6 at 6 at 7 https://gisao.genome.tugraz.at 8 and 9 all 8 and 15 viewed 9 all 10 the 9 all 12 data 9 all 13 can 10 the 12 data 11 stored 12 data 13 can 14 be 14 be 15 viewed 15 viewed 16 with 16 with 19 account 17 a 19 account 18 guest 19 account a new muscle - training method , " hybrid training " , utilizing combined voluntary and electrical muscle contractions , is effective for increasing muscle [mass] and force on lower extremities in elderly people . 0 ###LEFT-WALL### 3 muscle 0 ###LEFT-WALL### 21 is 0 ###LEFT-WALL### 35 . 1 a 2 new 1 a 3 muscle 2 new 3 muscle 3 muscle 5 training 3 muscle 21 is 4 - 5 training 5 training 6 method 5 training 13 utilizing 5 training 20 , 6 method 10 training 7 , 8 " 7 , 10 training 9 hybrid 10 training 10 training 11 " 10 training 12 , 12 , 13 utilizing 13 utilizing 19 contractions 13 utilizing 20 , 14 combined 19 contractions 15 voluntary 16 and 16 and 17 electrical 16 and 19 contractions 18 muscle 19 contractions 21 is 22 effective 22 effective 23 for 22 effective 32 in 23 for 27 and 24 increasing 25 muscle 25 muscle 27 and 27 and 28 force 27 and 29 on 29 on 31 extremities 30 lower 31 extremities 32 in 34 people 33 elderly 34 people although skeletal muscle regulates glucose metabolism , partly by releasing interleukin ( il ) - 6 , the effects [of] hybrid training on glucose metabolism remains unclear . 0 ###LEFT-WALL### 22 training 0 ###LEFT-WALL### 26 remains 0 ###LEFT-WALL### 28 . 1 although 3 muscle 1 although 4 regulates 1 although 22 training 2 skeletal 3 muscle 3 muscle 4 regulates 4 regulates 6 metabolism 5 glucose 6 metabolism 6 metabolism 9 by 7 , 8 partly 7 , 9 by 9 by 10 releasing 9 by 17 , 10 releasing 11 interleukin 11 interleukin 13 il 11 interleukin 16 6 12 ( 13 il 13 il 14 ) 15 - 16 6 16 6 17 , 18 the 22 training 19 effects 22 training 21 hybrid 22 training 22 training 23 on 22 training 26 remains 23 on 25 metabolism 24 glucose 25 metabolism 26 remains 27 unclear the aim of this study was to investigate the effects of hybrid training on glucose metabolism and serum il - 6 levels in elderly people . 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 effects 8 investigate 14 on 9 the 10 effects 10 effects 11 of 11 of 13 training 12 hybrid 13 training 14 on 17 and 15 glucose 16 metabolism 16 metabolism 17 and 17 and 19 il 17 and 22 levels 18 serum 19 il 20 - 22 levels 21 6 22 levels 22 levels 23 in 22 levels 26 . 23 in 25 people 24 elderly 25 people hybrid training was performed on 7 elderly subjects . 0 ###LEFT-WALL### 2 training 0 ###LEFT-WALL### 4 performed 0 ###LEFT-WALL### 9 . 1 hybrid 2 training 2 training 3 was 3 was 4 performed 4 performed 5 on 5 on 8 subjects 6 7 8 subjects 7 elderly 8 subjects both quadriceps and hamstrings were contracted voluntarily or electrically [at] the same time for 19 min twice a week . 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 6 contracted 0 ###LEFT-WALL### 8 or 0 ###LEFT-WALL### 20 . 1 both 2 quadriceps 2 quadriceps 3 and 3 and 4 hamstrings 3 and 5 were 5 were 6 contracted 6 contracted 7 voluntarily 8 or 12 same 8 or 13 time 9 electrically 12 same 11 the 12 same 12 same 13 time 13 time 14 for 13 time 17 twice 13 time 19 week 14 for 16 min 15 19 16 min 18 a 19 week the effects on glucose metabolism and serum il - 6 levels were evaluated after 12 weeks of hybrid training . 0 ###LEFT-WALL### 6 and 0 ###LEFT-WALL### 20 . 1 the 2 effects 2 effects 3 on 2 effects 6 and 3 on 5 metabolism 4 glucose 5 metabolism 6 and 7 serum 6 and 8 il 6 and 13 evaluated 8 il 11 levels 8 il 12 were 8 il 13 evaluated 9 - 10 6 10 6 11 levels 11 levels 12 were 13 evaluated 14 after 14 after 16 weeks 15 12 16 weeks 16 weeks 17 of 17 of 19 training 18 hybrid 19 training all of the subjects completed the study , and no severe adverse events developed during the study period . 0 ###LEFT-WALL### 1 all 0 ###LEFT-WALL### 5 completed 0 ###LEFT-WALL### 19 . 1 all 2 of 1 all 5 completed 2 of 4 subjects 3 the 4 subjects 5 completed 9 and 6 the 9 and 7 study 9 and 8 , 9 and 9 and 13 events 9 and 14 developed 10 no 13 events 11 severe 13 events 12 adverse 13 events 14 developed 15 during 15 during 18 period 16 the 18 period 17 study 18 period there were no significant differences in body mass index [,] serum insulin levels , homeostasis model assessment for insulin resistance values , or hemoglobin a1c values after hybrid training . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 were 0 ###LEFT-WALL### 14 , 0 ###LEFT-WALL### 30 . 1 there 2 were 2 were 5 differences 2 were 6 in 3 no 5 differences 4 significant 5 differences 6 in 13 levels 7 body 8 mass 8 mass 12 insulin 9 index 12 insulin 11 serum 12 insulin 12 insulin 13 levels 14 , 15 homeostasis 14 , 26 values 15 homeostasis 16 model 16 model 17 assessment 16 model 18 for 18 for 23 or 19 insulin 20 resistance 20 resistance 21 values 21 values 23 or 22 , 23 or 23 or 24 hemoglobin 23 or 25 a1c 23 or 26 values 25 a1c 26 values 26 values 27 after 27 after 29 training 28 hybrid 29 training however , fasting blood glucose levels were significantly decreased after hybrid training ( 114 ± 13 vs [.] 103 ± 9 mg·dl ( - 1 ) [;] p = 0.0340 ) . 0 ###LEFT-WALL### 6 levels 0 ###LEFT-WALL### 9 decreased 0 ###LEFT-WALL### 32 . 1 however 2 , 1 however 6 levels 3 fasting 6 levels 4 blood 6 levels 5 glucose 6 levels 6 levels 7 were 7 were 9 decreased 8 significantly 9 decreased 9 decreased 10 after 10 after 12 training 11 hybrid 12 training 12 training 15 ± 13 ( 15 ± 14 114 15 ± 15 ± 16 13 15 ± 17 vs 15 ± 31 ) 17 vs 20 ± 19 103 20 ± 20 ± 21 9 20 ± 22 mg·dl 20 ± 25 1 20 ± 29 = 21 9 22 mg·dl 23 ( 25 1 24 - 25 1 25 1 26 ) 28 p 29 = 29 = 30 0.0340 29 = 31 ) in addition , all 7 subjects showed a decrease in serum il - 6 levels after hybrid training , and this decrease was statistically significant ( 44.0 ± 35.6 vs [.] 14.6 ± 10.5 pg·ml [(] - 1 [ )( p = 0.0180 ) . 0 ###LEFT-WALL### 6 subjects 0 ###LEFT-WALL### 7 showed 1 in 2 addition 1 in 3 , 1 in 6 subjects 4 all 5 7 5 7 6 subjects 6 subjects 7 showed 7 showed 9 decrease 7 showed 15 levels 7 showed 16 after 8 a 9 decrease 9 decrease 10 in 10 in 12 il 11 serum 12 il 13 - 14 6 14 6 15 levels 16 after 22 decrease 16 after 23 was 17 hybrid 18 training 18 training 20 and 19 , 20 and 20 and 21 this 20 and 22 decrease 22 decrease 23 was 23 was 24 statistically 23 was 25 significant 25 significant 37 - 26 ( 37 - 27 44.0 28 ± 28 ± 29 35.6 28 ± 35 pg·ml 28 ± 37 - 29 35.6 30 vs 29 35.6 35 pg·ml 30 vs 33 ± 32 14.6 33 ± 33 ± 34 10.5 37 - 38 1 37 - 45 . 38 1 42 = 41 p 42 = 42 = 43 0.0180 42 = 44 ) furthermore , there was a significant correlation between changes in serum il - 6 levels and changes in fasting blood glucose levels [(] ρ = 0.883 [;] p = 0.0306 ) . 0 ###LEFT-WALL### 3 there 0 ###LEFT-WALL### 4 was 0 ###LEFT-WALL### 32 . 1 furthermore 2 , 1 furthermore 3 there 3 there 4 was 4 was 7 correlation 5 a 6 significant 5 a 7 correlation 6 significant 7 correlation 7 correlation 8 between 7 correlation 10 in 7 correlation 14 6 7 correlation 16 and 8 between 9 changes 10 in 12 il 11 serum 12 il 13 - 14 6 14 6 16 and 15 levels 16 and 16 and 17 changes 16 and 18 in 16 and 25 = 18 in 22 levels 19 fasting 22 levels 20 blood 22 levels 21 glucose 22 levels 24 ρ 25 = 25 = 29 = 26 0.883 29 = 28 p 29 = 29 = 30 0.0306 29 = 31 ) in this study , we showed the safety and good adherence of hybrid training for lower extremities in elderly people . 0 ###LEFT-WALL### 5 we 0 ###LEFT-WALL### 6 showed 0 ###LEFT-WALL### 21 . 1 in 3 study 1 in 4 , 1 in 5 we 2 this 3 study 5 we 6 showed 6 showed 11 adherence 6 showed 18 in 7 the 11 adherence 8 safety 9 and 9 and 10 good 9 and 11 adherence 11 adherence 12 of 12 of 14 training 13 hybrid 14 training 14 training 15 for 15 for 17 extremities 16 lower 17 extremities 18 in 20 people 19 elderly 20 people furthermore , hybrid training decreased fasting blood glucose and serum il - 6 levels in elderly people . 0 ###LEFT-WALL### 4 training 0 ###LEFT-WALL### 5 decreased 0 ###LEFT-WALL### 12 - 0 ###LEFT-WALL### 18 . 1 furthermore 2 , 1 furthermore 4 training 3 hybrid 4 training 4 training 5 decreased 5 decreased 9 and 6 fasting 7 blood 7 blood 8 glucose 8 glucose 9 and 9 and 11 il 10 serum 11 il 12 - 14 levels 13 6 14 levels 14 levels 15 in 15 in 17 people 16 elderly 17 people none background : premalignancies resulting from photodamage [,] such as actinic keratosis and carcinoma in situ , can be treated with various modalities . 0 ###LEFT-WALL### 1 none 0 ###LEFT-WALL### 17 , 0 ###LEFT-WALL### 24 . 1 none 2 background 1 none 6 from 1 none 17 , 2 background 3 : 3 : 4 premalignancies 4 premalignancies 5 resulting 5 resulting 6 from 7 photodamage 13 and 7 photodamage 16 situ 7 photodamage 17 , 9 such 12 keratosis 10 as 11 actinic 11 actinic 12 keratosis 12 keratosis 13 and 13 and 14 carcinoma 15 in 16 situ 17 , 18 can 18 can 19 be 19 be 20 treated 20 treated 21 with 21 with 23 modalities 22 various 23 modalities most of these treatments may reverse or treat these conditions although they often involve considerable skin irritation over a long period of time , [are] very uncomfortable for the patients or they need many office visits [and] sometimes are very expensive , such as photodynamic therapy [(] [pdt] ) . 0 ###LEFT-WALL### 4 treatments 0 ###LEFT-WALL### 7 or 0 ###LEFT-WALL### 24 , 0 ###LEFT-WALL### 50 . 1 most 2 of 1 most 4 treatments 2 of 4 treatments 3 these 4 treatments 4 treatments 5 may 5 may 7 or 6 reverse 7 or 7 or 8 treat 7 or 11 although 8 treat 10 conditions 9 these 10 conditions 11 although 12 they 11 although 14 involve 12 they 14 involve 13 often 14 involve 14 involve 17 irritation 14 involve 18 over 15 considerable 16 skin 16 skin 17 irritation 18 over 21 period 19 a 21 period 20 long 21 period 21 period 22 of 22 of 23 time 24 , 27 uncomfortable 24 , 39 are 26 very 27 uncomfortable 27 uncomfortable 28 for 27 uncomfortable 39 are 28 for 33 need 29 the 30 patients 30 patients 31 or 31 or 32 they 31 or 33 need 34 many 36 visits 35 office 36 visits 36 visits 39 are 38 sometimes 39 are 39 are 41 expensive 40 very 41 expensive 41 expensive 44 as 42 , 44 as 43 such 44 as 44 as 46 therapy 44 as 49 ) 45 photodynamic 46 therapy objective : to study the effectiveness of a mixed session of q - switched ktp 532 [nm] and nd:yag 1064 nm laser treatment on precancerous lesions resulting from solar damage . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 2 : 3 to 2 : 4 study 3 to 4 study 4 study 6 effectiveness 5 the 6 effectiveness 6 effectiveness 7 of 7 of 10 session 8 a 10 session 9 mixed 10 session 10 session 11 of 10 session 18 and 11 of 12 q 13 - 18 and 14 switched 15 ktp 15 ktp 16 532 15 ktp 18 and 18 and 23 treatment 18 and 24 on 18 and 27 resulting 18 and 31 . 19 nd:yag 23 treatment 20 1064 21 nm 21 nm 23 treatment 22 laser 23 treatment 24 on 26 lesions 25 precancerous 26 lesions 27 resulting 28 from 28 from 30 damage 29 solar 30 damage methods : ten patients with long [-] standing actinic damage/keratosis or carcinoma in situ were subjected to only one session of [mixed] q - switched ktp 532 [nm] and nd:yag 1064 nm laser treatment . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 4 patients 2 : 16 subjected 3 ten 4 patients 4 patients 5 with 4 patients 15 were 5 with 8 standing 6 long 8 standing 8 standing 11 or 8 standing 14 situ 9 actinic 10 damage/keratosis 10 damage/keratosis 11 or 11 or 12 carcinoma 13 in 14 situ 15 were 16 subjected 16 subjected 17 to 17 to 20 session 18 only 19 one 19 one 20 session 20 session 21 of 20 session 29 and 21 of 23 q 24 - 29 and 25 switched 26 ktp 26 ktp 27 532 26 ktp 29 and 29 and 34 treatment 29 and 35 . 30 nd:yag 33 laser 31 1064 32 nm 32 nm 33 laser 33 laser 34 treatment lesions were evenly and repeatedly scanned with both wavelengths until light pain or purpura presented . 0 ###LEFT-WALL### 1 lesions 0 ###LEFT-WALL### 6 scanned 0 ###LEFT-WALL### 16 . 1 lesions 2 were 2 were 4 and 2 were 6 scanned 3 evenly 4 and 4 and 5 repeatedly 6 scanned 7 with 7 with 9 wavelengths 8 both 9 wavelengths 9 wavelengths 10 until 9 wavelengths 15 presented 10 until 13 or 11 light 12 pain 12 pain 13 or 13 or 14 purpura results : all patients responded extremely well within a period of 20 days , with just one session , with virtually no pain , minimum irritation , no down time at all and excellent cosmetic outcome . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 37 . 2 : 4 patients 2 : 5 responded 3 all 4 patients 4 patients 5 responded 5 responded 7 well 5 responded 8 within 5 responded 15 with 5 responded 30 time 5 responded 31 at 6 extremely 7 well 8 within 10 period 9 a 10 period 10 period 11 of 11 of 13 days 12 20 13 days 14 , 15 with 15 with 18 session 15 with 27 , 16 just 17 one 17 one 18 session 18 session 20 with 18 session 26 irritation 19 , 20 with 20 with 23 pain 20 with 24 , 21 virtually 22 no 22 no 23 pain 24 , 26 irritation 25 minimum 26 irritation 26 irritation 27 , 28 no 30 time 29 down 30 time 31 at 33 and 32 all 33 and 33 and 36 outcome 34 excellent 36 outcome 35 cosmetic 36 outcome conclusion : the use of a mixed q - [switched] 532 nm [and] nd:yag 1064 nm laser session seems to be ideal for treating precancerous lesions resulting [from] photodamage since it can be a fast , painless and simple office procedure with no down time and minimum discomfort for the patient . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 52 . 2 : 4 use 2 : 29 photodamage 3 the 4 use 4 use 5 of 4 use 19 seems 5 of 18 session 6 a 18 session 7 mixed 17 laser 8 q 9 - 9 - 12 nm 9 - 17 laser 11 532 12 nm 14 nd:yag 17 laser 15 1064 16 nm 16 nm 17 laser 17 laser 18 session 19 seems 20 to 19 seems 21 be 20 to 21 be 21 be 22 ideal 21 be 23 for 23 for 26 lesions 24 treating 26 lesions 25 precancerous 26 lesions 26 lesions 27 resulting 26 lesions 29 photodamage 29 photodamage 30 since 29 photodamage 48 discomfort 29 photodamage 49 for 30 since 31 it 30 since 33 be 31 it 32 can 32 can 33 be 34 a 35 fast 34 a 48 discomfort 35 fast 36 , 35 fast 48 discomfort 37 painless 38 and 38 and 39 simple 38 and 48 discomfort 40 office 48 discomfort 41 procedure 42 with 41 procedure 46 and 42 with 45 time 43 no 45 time 44 down 45 time 46 and 47 minimum 46 and 48 discomfort 49 for 51 patient 50 the 51 patient this method proves to be much more selective than traditional intense pulse light ( ipl ) photorejuvenation . 0 ###LEFT-WALL### 2 method 0 ###LEFT-WALL### 3 proves 0 ###LEFT-WALL### 18 . 1 this 2 method 2 method 3 proves 3 proves 4 to 3 proves 5 be 4 to 5 be 5 be 8 selective 6 much 7 more 7 more 8 selective 8 selective 9 than 9 than 17 photorejuvenation 10 traditional 12 pulse 11 intense 12 pulse 12 pulse 17 photorejuvenation 13 light 15 ipl 13 light 17 photorejuvenation 14 ( 15 ipl 15 ipl 16 ) background : hyaluronic acid ( ha ) fillers such as restylane ( [®] [ )( frequently used for the correction of facial soft tissue defects . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 1 background 2 : 2 : 3 hyaluronic 3 hyaluronic 4 acid 3 hyaluronic 8 fillers 4 acid 6 ha 4 acid 8 fillers 5 ( 6 ha 6 ha 7 ) 8 fillers 10 as 9 such 10 as 10 as 11 restylane 11 restylane 17 used 12 ( 17 used 16 frequently 17 used 17 used 18 for 17 used 26 . 18 for 20 correction 19 the 20 correction 20 correction 21 of 21 of 25 defects 22 facial 24 tissue 23 soft 24 tissue 24 tissue 25 defects objective : to compare the efficacy and safety of a novel ha filler , emervel ( [®] [ )(classic , with those of restylane in the treatment of moderate nasolabial folds . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 32 . 2 : 3 to 2 : 4 compare 3 to 4 compare 4 compare 7 and 5 the 7 and 6 efficacy 7 and 7 and 8 safety 7 and 9 of 7 and 21 with 7 and 23 of 9 of 13 filler 10 a 13 filler 11 novel 13 filler 12 ha 13 filler 13 filler 15 emervel 14 , 15 emervel 15 emervel 19 )(classic 15 emervel 20 , 16 ( 19 )(classic 19 )(classic 20 , 21 with 22 those 23 of 24 restylane 24 restylane 25 in 24 restylane 28 of 25 in 27 treatment 26 the 27 treatment 28 of 31 folds 29 moderate 31 folds 30 nasolabial 31 folds methods : this was a split - face , randomized [and] evaluator - blinded comparison study . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 3 this 2 : 4 was 2 : 7 - 3 this 4 was 4 was 6 split 5 a 6 split 7 - 8 face 7 - 9 , 7 - 17 . 9 , 12 evaluator 9 , 13 - 10 randomized 12 evaluator 13 - 16 study 14 blinded 15 comparison 15 comparison 16 study subjects were randomized to receive an injection of emervel classic or restylane on their left or right side . 0 ###LEFT-WALL### 1 subjects 0 ###LEFT-WALL### 3 randomized 0 ###LEFT-WALL### 19 . 1 subjects 2 were 2 were 3 randomized 3 randomized 4 to 4 to 5 receive 5 receive 7 injection 5 receive 13 on 6 an 7 injection 7 injection 8 of 8 of 11 or 9 emervel 10 classic 10 classic 11 or 11 or 12 restylane 13 on 16 or 14 their 15 left 15 left 16 or 16 or 18 side 17 right 18 side efficacy was [evaluated] based on the change in wrinkle severity rating score ( wsrs ) from baseline . 0 ###LEFT-WALL### 1 efficacy 0 ###LEFT-WALL### 4 based 0 ###LEFT-WALL### 18 . 1 efficacy 2 was 2 was 4 based 4 based 5 on 4 based 8 in 4 based 16 from 5 on 7 change 6 the 7 change 8 in 14 wsrs 9 wrinkle 10 severity 10 severity 11 rating 11 rating 12 score 12 score 14 wsrs 13 ( 14 wsrs 14 wsrs 15 ) 16 from 17 baseline local tolerability [was] assessed based [on] subject diary , which recorded the severity of erythema , oedema/swelling , bruising , pain/tenderness and pruritus during the first 3 weeks after injection . 0 ###LEFT-WALL### 8 diary 0 ###LEFT-WALL### 9 , 0 ###LEFT-WALL### 31 . 1 local 4 assessed 2 tolerability 4 assessed 4 assessed 7 subject 5 based 7 subject 7 subject 8 diary 9 , 10 which 9 , 11 recorded 10 which 11 recorded 11 recorded 22 and 11 recorded 24 during 11 recorded 29 after 12 the 22 and 13 severity 14 of 13 severity 22 and 14 of 21 pain/tenderness 15 erythema 17 oedema/swelling 15 erythema 20 , 15 erythema 21 pain/tenderness 16 , 17 oedema/swelling 17 oedema/swelling 19 bruising 17 oedema/swelling 20 , 18 , 19 bruising 19 bruising 20 , 22 and 23 pruritus 24 during 26 first 25 the 26 first 27 3 28 weeks 28 weeks 29 after 29 after 30 injection results : the interim results 6 months after injection are reported . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 5 results 2 : 11 reported 2 : 12 . 3 the 5 results 4 interim 5 results 5 results 8 after 5 results 10 are 6 6 7 months 7 months 8 after 8 after 9 injection 10 are 11 reported at [week] 24 , the mean improvement in wsrs from baseline was 0.83 ± 0.51 for emervel classic , similar to that for restylane ( 0.90 ± 0.57 ) . 0 ###LEFT-WALL### 7 improvement 0 ###LEFT-WALL### 12 was 0 ###LEFT-WALL### 30 . 1 at 3 24 1 at 4 , 1 at 7 improvement 5 the 7 improvement 6 mean 7 improvement 7 improvement 8 in 7 improvement 12 was 8 in 9 wsrs 9 wsrs 10 from 10 from 11 baseline 12 was 14 ± 13 0.83 14 ± 14 ± 15 0.51 14 ± 16 for 16 for 18 classic 17 emervel 18 classic 18 classic 20 similar 19 , 20 similar 20 similar 21 to 20 similar 23 for 20 similar 29 ) 21 to 22 that 23 for 24 restylane 24 restylane 27 ± 25 ( 27 ± 26 0.90 27 ± 27 ± 28 0.57 27 ± 29 ) a similar volume of both fillers was injected . 0 ###LEFT-WALL### 3 volume 0 ###LEFT-WALL### 8 injected 0 ###LEFT-WALL### 9 . 1 a 2 similar 1 a 3 volume 2 similar 3 volume 3 volume 4 of 3 volume 7 was 4 of 6 fillers 5 both 6 fillers 7 was 8 injected most local tolerability events were mild and transient . 0 ###LEFT-WALL### 4 events 0 ###LEFT-WALL### 5 were 0 ###LEFT-WALL### 9 . 1 most 2 local 2 local 3 tolerability 3 tolerability 4 events 4 events 5 were 5 were 7 and 6 mild 7 and 7 and 8 transient erythema , oedema/swelling and pain/tenderness were significantly less severe and disappeared faster with emervel classic than with restylane ( at least p < 0.05 ) . 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 26 . 1 erythema 2 , 2 , 3 oedema/swelling 2 , 4 and 4 and 5 pain/tenderness 4 and 10 and 6 were 7 significantly 6 were 9 severe 6 were 10 and 8 less 9 severe 10 and 11 disappeared 10 and 12 faster 10 and 13 with 10 and 16 than 13 with 15 classic 14 emervel 15 classic 16 than 17 with 17 with 18 restylane 18 restylane 23 < 19 ( 21 least 19 ( 23 < 20 at 21 least 22 p 23 < 23 < 24 0.05 23 < 25 ) conclusion : emervel classic provides similar efficacy and better overall local tolerability compared with restylane 6 months after treatment of moderate nasolabial folds . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 24 . 1 conclusion 2 : 2 : 3 emervel 3 emervel 4 classic 3 emervel 5 provides 4 classic 5 provides 5 provides 8 and 5 provides 14 with 5 provides 18 after 6 similar 7 efficacy 7 efficacy 8 and 8 and 12 tolerability 8 and 13 compared 9 better 11 local 10 overall 11 local 11 local 12 tolerability 14 with 15 restylane 16 6 17 months 17 months 18 after 18 after 19 treatment 19 treatment 20 of 20 of 23 folds 21 moderate 23 folds 22 nasolabial 23 folds the neodymium:yttrium - aluminum - garnet ( nd:yag ) [laser] is a popular [non] - ablative treatment used for skin rejuvenation . 0 ###LEFT-WALL### 2 neodymium:yttrium 0 ###LEFT-WALL### 11 is 0 ###LEFT-WALL### 22 . 1 the 2 neodymium:yttrium 2 neodymium:yttrium 4 aluminum 2 neodymium:yttrium 6 garnet 2 neodymium:yttrium 11 is 3 - 4 aluminum 4 aluminum 5 - 5 - 6 garnet 6 garnet 8 nd:yag 6 garnet 9 ) 7 ( 8 nd:yag 8 nd:yag 9 ) 11 is 17 treatment 12 a 13 popular 12 a 17 treatment 13 popular 15 - 13 popular 17 treatment 16 ablative 17 treatment 17 treatment 18 used 18 used 19 for 19 for 21 rejuvenation 20 skin 21 rejuvenation the purpose of this prospective study was to evaluate the clinical effects , coupled with a quantitative assessment , of the histological changes in response to nd:yag 1320 - [nm] laser treatment of periocular wrinkles . 0 ###LEFT-WALL### 2 purpose 0 ###LEFT-WALL### 13 , 0 ###LEFT-WALL### 36 . 1 the 2 purpose 2 purpose 3 of 2 purpose 13 , 3 of 6 study 4 this 5 prospective 5 prospective 6 study 7 was 8 to 7 was 9 evaluate 7 was 13 , 8 to 9 evaluate 9 evaluate 12 effects 10 the 12 effects 11 clinical 12 effects 13 , 14 coupled 13 , 15 with 13 , 32 treatment 15 with 18 assessment 16 a 18 assessment 17 quantitative 18 assessment 18 assessment 20 of 19 , 20 of 20 of 23 changes 20 of 29 - 21 the 23 changes 22 histological 23 changes 23 changes 25 response 23 changes 26 to 24 in 25 response 26 to 27 nd:yag 27 nd:yag 28 1320 31 laser 32 treatment 32 treatment 33 of 33 of 35 wrinkles 34 periocular 35 wrinkles six volunteers with fitzpatrick skin types iii and iv and glogau class i - ii wrinkles were subjected to 3 months of nd:yag 1320 [-] nm treatment in the periocular area ( six sessions at 2 - week intervals ) . 0 ###LEFT-WALL### 2 volunteers 0 ###LEFT-WALL### 5 skin 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 41 . 1 six 2 volunteers 2 volunteers 3 with 2 volunteers 5 skin 3 with 4 fitzpatrick 5 skin 6 types 6 types 7 iii 8 and 10 and 8 and 18 subjected 9 iv 10 and 10 and 12 class 10 and 14 - 10 and 15 ii 10 and 16 wrinkles 10 and 17 were 11 glogau 12 class 12 class 13 i 15 ii 16 wrinkles 17 were 18 subjected 18 subjected 19 to 18 subjected 28 in 19 to 21 months 20 3 21 months 21 months 22 of 22 of 27 treatment 23 nd:yag 27 treatment 24 1320 26 nm 26 nm 27 treatment 28 in 31 area 29 the 31 area 30 periocular 31 area 31 area 34 sessions 32 ( 34 sessions 33 six 34 sessions 34 sessions 35 at 34 sessions 40 ) 35 at 36 2 36 2 39 intervals 37 - 39 intervals 38 week 39 intervals 39 intervals 40 ) volunteers were photographed , and skin [biopsies] were obtained at baseline as well as 3 and 6 months after the start of treatments . 0 ###LEFT-WALL### 1 volunteers 0 ###LEFT-WALL### 3 photographed 0 ###LEFT-WALL### 5 and 0 ###LEFT-WALL### 24 . 1 volunteers 2 were 2 were 3 photographed 4 , 5 and 5 and 6 skin 5 and 9 obtained 6 skin 8 were 8 were 9 obtained 9 obtained 10 at 9 obtained 14 as 9 obtained 19 after 10 at 11 baseline 12 as 13 well 13 well 14 as 14 as 18 months 15 3 16 and 16 and 17 6 16 and 18 months 19 after 21 start 20 the 21 start 21 start 22 of 22 of 23 treatments quantitative evaluation [of] total elastin , newly synthesized tropoelastin , collagen types i , iii [and] [vii] , and newly synthesized collagen was performed using a computerized morphometric analysis . 0 ###LEFT-WALL### 5 elastin 0 ###LEFT-WALL### 6 , 0 ###LEFT-WALL### 30 . 1 quantitative 2 evaluation 2 evaluation 5 elastin 4 total 5 elastin 6 , 9 tropoelastin 6 , 10 , 7 newly 8 synthesized 8 synthesized 9 tropoelastin 10 , 11 collagen 10 , 19 and 11 collagen 12 types 12 types 13 i 12 types 15 iii 14 , 15 iii 15 iii 18 , 18 , 19 and 19 and 22 collagen 19 and 24 performed 20 newly 21 synthesized 21 synthesized 22 collagen 22 collagen 23 was 23 was 24 performed 24 performed 25 using 25 using 29 analysis 26 a 27 computerized 26 a 29 analysis 27 computerized 29 analysis 28 morphometric 29 analysis a noticeable clinical and histological improvement was observed after nd:yag 1320 - [nm] treatment . 0 ###LEFT-WALL### 6 improvement 0 ###LEFT-WALL### 12 - 0 ###LEFT-WALL### 15 . 1 a 2 noticeable 1 a 6 improvement 2 noticeable 6 improvement 3 clinical 4 and 4 and 5 histological 4 and 6 improvement 6 improvement 7 was 7 was 8 observed 8 observed 9 after 9 after 10 nd:yag 10 nd:yag 11 1320 11 1320 12 - 12 - 14 treatment collagen types [i] [,] iii and vii , as well as newly synthesized collagen , together [with] tropoelastin showed a statistically significant increase in response to treatment , while the mean level of total elastin was significantly decreased after treatment . 0 ###LEFT-WALL### 1 collagen 0 ###LEFT-WALL### 2 types 0 ###LEFT-WALL### 6 and 1 collagen 2 types 2 types 5 iii 6 and 15 , 6 and 18 tropoelastin 7 vii 11 as 8 , 11 as 9 as 10 well 10 well 11 as 11 as 14 collagen 11 as 15 , 12 newly 13 synthesized 13 synthesized 14 collagen 16 together 18 tropoelastin 18 tropoelastin 19 showed 19 showed 23 increase 19 showed 29 while 20 a 21 statistically 20 a 23 increase 21 statistically 22 significant 22 significant 23 increase 23 increase 25 response 23 increase 26 to 24 in 25 response 26 to 27 treatment 28 , 29 while 29 while 32 level 29 while 38 decreased 29 while 41 . 30 the 32 level 31 mean 32 level 32 level 33 of 32 level 36 was 33 of 35 elastin 34 total 35 elastin 36 was 37 significantly 36 was 38 decreased 38 decreased 39 after 39 after 40 treatment our data suggest that nd:yag 1320 [nm] is an effective treatment for skin rejuvenation as it stimulates the repair processes , and reverses the clinical , as well as the histopathological , signs of skin aging . 0 ###LEFT-WALL### 8 is 1 our 2 data 2 data 3 suggest 3 suggest 4 that 4 that 5 nd:yag 4 that 8 is 5 nd:yag 6 1320 8 is 11 treatment 8 is 22 and 9 an 11 treatment 10 effective 11 treatment 11 treatment 12 for 12 for 14 rejuvenation 13 skin 14 rejuvenation 14 rejuvenation 15 as 15 as 16 it 17 stimulates 20 processes 17 stimulates 22 and 18 the 20 processes 19 repair 20 processes 21 , 22 and 22 and 23 reverses 22 and 27 as 23 reverses 25 clinical 24 the 25 clinical 26 , 27 as 27 as 28 well 27 as 37 . 28 well 36 aging 29 as 33 signs 29 as 36 aging 30 the 33 signs 31 histopathological 32 , 31 histopathological 33 signs 33 signs 34 of 33 signs 36 aging 34 of 35 skin 36 aging 37 . none none none none none following an increase in length and width during childhood and adolescence , skeletal growth is generally assumed to stop . 0 ###LEFT-WALL### 1 none 0 ###LEFT-WALL### 22 assumed 2 none 3 none 3 none 4 none 4 none 5 none 5 none 6 following 6 following 19 growth 6 following 20 is 6 following 22 assumed 7 an 8 increase 8 increase 9 in 8 increase 11 and 9 in 10 length 11 and 12 width 11 and 13 during 11 and 15 and 13 during 14 childhood 15 and 16 adolescence 15 and 17 , 15 and 19 growth 18 skeletal 19 growth 19 growth 20 is 21 generally 22 assumed 22 assumed 23 to 22 assumed 25 . 23 to 24 stop this study investigates the influence of aging on the dimensions of the pelvis and the l4 lumbar vertebra during adulthood . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 investigates 0 ###LEFT-WALL### 21 . 1 this 2 study 2 study 3 investigates 3 investigates 5 influence 3 investigates 8 on 3 investigates 19 during 4 the 5 influence 5 influence 6 of 6 of 7 aging 8 on 14 and 9 the 10 dimensions 10 dimensions 11 of 10 dimensions 14 and 11 of 13 pelvis 12 the 13 pelvis 14 and 18 vertebra 15 the 18 vertebra 16 l4 18 vertebra 17 lumbar 18 vertebra 19 during 20 adulthood the dimensions of the pelvis , l4 vertebra , and femoral heads were calculated for 246 patients who had received pelvic and abdominal computed tomography scans from the unc health care system . 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 33 . 1 the 2 dimensions 2 dimensions 3 of 2 dimensions 6 , 3 of 5 pelvis 4 the 5 pelvis 6 , 8 vertebra 6 , 10 and 7 l4 8 vertebra 9 , 10 and 10 and 12 heads 10 and 13 were 11 femoral 12 heads 13 were 14 calculated 14 calculated 15 for 14 calculated 27 from 15 for 17 patients 16 246 17 patients 17 patients 18 who 17 patients 19 had 18 who 19 had 19 had 20 received 20 received 22 and 20 received 24 computed 21 pelvic 22 and 22 and 23 abdominal 24 computed 25 tomography 24 computed 26 scans 25 tomography 26 scans 27 from 32 system 28 the 32 system 29 unc 30 health 30 health 31 care 31 care 32 system linear regression analysis determined the significance of relationships between age and width of the pelvis . 0 ###LEFT-WALL### 3 analysis 0 ###LEFT-WALL### 4 determined 0 ###LEFT-WALL### 16 . 1 linear 2 regression 2 regression 3 analysis 3 analysis 4 determined 4 determined 6 significance 4 determined 9 between 5 the 6 significance 6 significance 7 of 7 of 8 relationships 9 between 11 and 10 age 11 and 11 and 12 width 11 and 13 of 13 of 15 pelvis 14 the 15 pelvis the pelvic inlet did not enlarge [over] time while the distance between the hips and the femoral head diameter did significantly increase . 0 ###LEFT-WALL### 3 inlet 0 ###LEFT-WALL### 6 enlarge 0 ###LEFT-WALL### 23 . 1 the 3 inlet 2 pelvic 3 inlet 3 inlet 4 did 4 did 5 not 4 did 6 enlarge 6 enlarge 8 time 6 enlarge 9 while 9 while 11 distance 9 while 22 increase 10 the 11 distance 11 distance 12 between 11 distance 20 did 12 between 15 and 13 the 14 hips 14 hips 15 and 15 and 19 diameter 16 the 19 diameter 17 femoral 18 head 18 head 19 diameter 20 did 22 increase 21 significantly 22 increase the height of l4 did not increase over time , but the l4 width did increase . 0 ###LEFT-WALL### 2 height 0 ###LEFT-WALL### 7 increase 0 ###LEFT-WALL### 11 but 0 ###LEFT-WALL### 17 . 1 the 2 height 2 height 3 of 2 height 5 did 3 of 4 l4 5 did 6 not 5 did 7 increase 7 increase 8 over 8 over 9 time 10 , 11 but 11 but 14 width 11 but 16 increase 12 the 14 width 13 l4 14 width 14 width 15 did 15 did 16 increase these correlations were seen in both genders . 0 ###LEFT-WALL### 2 correlations 0 ###LEFT-WALL### 4 seen 0 ###LEFT-WALL### 8 . 1 these 2 correlations 2 correlations 3 were 3 were 4 seen 4 seen 5 in 5 in 7 genders 6 both 7 genders surprisingly , our results suggest that the pelvis and l4 vertebra increase in width after skeletal maturity and cessation of longitudinal growth . 0 ###LEFT-WALL### 4 results 0 ###LEFT-WALL### 5 suggest 0 ###LEFT-WALL### 23 . 1 surprisingly 2 , 1 surprisingly 4 results 3 our 4 results 4 results 5 suggest 5 suggest 6 that 6 that 9 and 6 that 12 increase 7 the 8 pelvis 8 pelvis 9 and 9 and 11 vertebra 10 l4 11 vertebra 12 increase 13 in 12 increase 15 after 13 in 14 width 15 after 18 and 16 skeletal 17 maturity 17 maturity 18 and 18 and 19 cessation 18 and 20 of 20 of 22 growth 21 longitudinal 22 growth colorectal cancer ( crc ) is the second most common cause of death due to cancer causing death in europe , accounting for more than 200,000 deaths per year . 0 ###LEFT-WALL### 2 cancer 0 ###LEFT-WALL### 6 is 1 colorectal 2 cancer 2 cancer 4 crc 2 cancer 6 is 3 ( 4 crc 4 crc 5 ) 6 is 8 second 7 the 8 second 8 second 10 common 8 second 17 causing 8 second 22 accounting 9 most 10 common 10 common 11 cause 10 common 15 to 11 cause 12 of 12 of 13 death 14 due 15 to 15 to 16 cancer 17 causing 18 death 18 death 19 in 19 in 20 europe 21 , 22 accounting 22 accounting 23 for 22 accounting 30 . 23 for 27 deaths 24 more 25 than 25 than 26 200,000 26 200,000 27 deaths 27 deaths 28 per 28 per 29 year prognosis strongly depends on stage at diagnosis , and the disease can be cured in most cases if diagnosed at an early stage . 0 ###LEFT-WALL### 1 prognosis 0 ###LEFT-WALL### 3 depends 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 24 . 1 prognosis 3 depends 2 strongly 3 depends 3 depends 5 stage 3 depends 6 at 4 on 5 stage 6 at 7 diagnosis 8 , 9 and 9 and 11 disease 9 and 14 cured 10 the 11 disease 11 disease 12 can 12 can 13 be 13 be 14 cured 14 cured 15 in 14 cured 18 if 15 in 17 cases 16 most 17 cases 18 if 19 diagnosed 19 diagnosed 20 at 20 at 23 stage 21 an 22 early 21 an 23 stage 22 early 23 stage we aimed to assess trends and recent developments in 5 - year relative survival in european countries , with a special focus on age , stage at diagnosis and anatomical cancer subsite . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 aimed 0 ###LEFT-WALL### 6 and 0 ###LEFT-WALL### 33 . 1 we 2 aimed 2 aimed 3 to 2 aimed 4 assess 3 to 4 assess 4 assess 5 trends 6 and 8 developments 6 and 25 , 7 recent 8 developments 8 developments 9 in 8 developments 19 with 8 developments 25 , 9 in 10 5 10 5 14 survival 11 - 14 survival 12 year 14 survival 13 relative 14 survival 14 survival 15 in 14 survival 18 , 15 in 17 countries 16 european 17 countries 19 with 21 special 20 a 21 special 22 focus 23 on 22 focus 25 , 23 on 24 age 25 , 26 stage 25 , 27 at 27 at 29 and 28 diagnosis 29 and 29 and 32 subsite 30 anatomical 31 cancer 31 cancer 32 subsite data from 25 population - based cancer registries from 16 european countries collected in the context of the eurocare - 4 project were analyzed . 0 ###LEFT-WALL### 8 registries 0 ###LEFT-WALL### 24 analyzed 0 ###LEFT-WALL### 25 . 1 data 8 registries 2 from 4 population 2 from 5 - 2 from 8 registries 3 25 4 population 6 based 7 cancer 7 cancer 8 registries 8 registries 9 from 8 registries 13 collected 8 registries 17 of 8 registries 23 were 9 from 12 countries 10 16 12 countries 11 european 12 countries 13 collected 14 in 14 in 16 context 15 the 16 context 17 of 19 eurocare 18 the 19 eurocare 19 eurocare 21 4 19 eurocare 22 project 20 - 21 4 21 4 22 project 23 were 24 analyzed using period analysis , age - [adjusted] and age - specific [5] - year relative survival was calculated by country , european region , stage and cancer subsite for time periods from 1988 - 1990 to 2000 - 2002 . 0 ###LEFT-WALL### 26 and 0 ###LEFT-WALL### 28 subsite 0 ###LEFT-WALL### 40 . 1 using 3 analysis 2 period 3 analysis 3 analysis 4 , 4 , 20 country 4 , 21 , 5 age 8 and 6 - 8 and 8 and 9 age 8 and 10 - 8 and 16 survival 8 and 19 by 8 and 20 country 11 specific 13 - 11 specific 15 relative 14 year 15 relative 15 relative 16 survival 16 survival 17 was 17 was 18 calculated 18 calculated 19 by 21 , 23 region 21 , 24 , 22 european 23 region 24 , 25 stage 24 , 26 and 26 and 27 cancer 26 and 28 subsite 28 subsite 29 for 28 subsite 34 - 28 subsite 36 to 29 for 31 periods 30 time 31 periods 32 from 34 - 33 1988 34 - 34 - 35 1990 36 to 38 - 37 2000 38 - 38 - 39 2002 survival substantially increased over time in all european regions . 0 ###LEFT-WALL### 1 survival 0 ###LEFT-WALL### 3 increased 0 ###LEFT-WALL### 10 . 1 survival 3 increased 2 substantially 3 increased 3 increased 4 over 3 increased 6 in 4 over 5 time 6 in 9 regions 7 all 9 regions 8 european 9 regions in general , increases were more pronounced [in] younger than in older patients , for earlier than [for] more advanced cancer stages and [for] rectum than for colon cancer . 0 ###LEFT-WALL### 4 increases 0 ###LEFT-WALL### 7 pronounced 0 ###LEFT-WALL### 14 , 0 ###LEFT-WALL### 30 . 1 in 2 general 2 general 3 , 2 general 4 increases 4 increases 5 were 5 were 6 more 5 were 7 pronounced 7 pronounced 9 younger 9 younger 10 than 10 than 11 in 11 in 13 patients 12 older 13 patients 14 , 15 for 14 , 20 advanced 15 for 19 more 16 earlier 19 more 17 than 19 more 19 more 20 advanced 20 advanced 23 and 20 advanced 26 than 20 advanced 27 for 21 cancer 22 stages 22 stages 23 and 23 and 25 rectum 27 for 29 cancer 28 colon 29 cancer substantial variation of crc survival between european countries and between age groups persisted and even tentatively increased over time . 0 ###LEFT-WALL### 2 variation 0 ###LEFT-WALL### 14 and 0 ###LEFT-WALL### 20 . 1 substantial 2 variation 2 variation 3 of 2 variation 14 and 3 of 5 survival 4 crc 5 survival 5 survival 9 and 6 between 8 countries 6 between 9 and 7 european 8 countries 9 and 10 between 10 between 12 groups 11 age 12 groups 13 persisted 14 and 14 and 17 increased 14 and 18 over 15 even 17 increased 16 tentatively 17 increased 18 over 19 time there is a huge potential for reducing the burden of crc in europe by more widespread and equal delivery of existing options of effective early detection and curative treatment to the european population . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 34 . 1 there 2 is 2 is 5 potential 3 a 4 huge 3 a 5 potential 4 huge 5 potential 5 potential 6 for 5 potential 10 of 6 for 7 reducing 7 reducing 9 burden 8 the 9 burden 10 of 11 crc 11 crc 12 in 12 in 13 europe 13 europe 14 by 13 europe 20 of 14 by 19 delivery 15 more 19 delivery 16 widespread 17 and 17 and 18 equal 17 and 19 delivery 20 of 22 options 21 existing 22 options 22 options 23 of 23 of 27 and 24 effective 26 detection 25 early 26 detection 26 detection 27 and 27 and 29 treatment 27 and 30 to 28 curative 29 treatment 30 to 33 population 31 the 33 population 32 european 33 population background : carbonylation is an irreversible modification caused by the introduction into proteins of carbonyl derivatives ( aldehydes and ketones ) , which can alter protein structure and function and lead to cellular dysfunction and tissue damage . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 38 . 2 : 3 carbonylation 2 : 4 is 2 : 22 , 3 carbonylation 4 is 4 is 7 modification 5 an 6 irreversible 5 an 7 modification 6 irreversible 7 modification 7 modification 8 caused 7 modification 12 into 8 caused 9 by 9 by 11 introduction 10 the 11 introduction 12 into 13 proteins 13 proteins 14 of 13 proteins 19 and 14 of 16 derivatives 15 carbonyl 16 derivatives 17 ( 19 and 18 aldehydes 19 and 19 and 20 ketones 19 and 21 ) 22 , 23 which 22 , 30 and 23 which 30 and 24 can 28 and 24 can 30 and 25 alter 27 structure 25 alter 28 and 26 protein 27 structure 28 and 29 function 30 and 31 lead 30 and 32 to 30 and 37 damage 32 to 35 and 33 cellular 34 dysfunction 34 dysfunction 35 and 35 and 36 tissue chronic uremia may be associated with an increased carbonyl [overload] ( " carbonyl stress " ) , though carbonyl formation has been proposed so far for major plasma proteins only . 0 ###LEFT-WALL### 4 be 0 ###LEFT-WALL### 17 , 0 ###LEFT-WALL### 31 . 1 chronic 2 uremia 2 uremia 3 may 3 may 4 be 4 be 5 associated 5 associated 6 with 6 with 9 carbonyl 7 an 9 carbonyl 8 increased 9 carbonyl 9 carbonyl 14 stress 11 ( 12 " 11 ( 14 stress 13 carbonyl 14 stress 14 stress 15 " 14 stress 16 ) 17 , 20 formation 17 , 23 proposed 18 though 19 carbonyl 18 though 20 formation 20 formation 21 has 21 has 22 been 22 been 23 proposed 23 proposed 25 far 23 proposed 26 for 23 proposed 30 only 24 so 25 far 26 for 29 proteins 27 major 28 plasma 28 plasma 29 proteins in this study we looked for evidence and for the targets of plasma protein carbonylation in patients on hemodialysis . 0 ###LEFT-WALL### 4 we 0 ###LEFT-WALL### 5 looked 0 ###LEFT-WALL### 20 . 1 in 3 study 1 in 4 we 2 this 3 study 4 we 5 looked 5 looked 8 and 5 looked 16 in 5 looked 18 on 6 for 7 evidence 6 for 8 and 8 and 9 for 9 for 11 targets 10 the 11 targets 11 targets 12 of 12 of 15 carbonylation 13 plasma 15 carbonylation 14 protein 15 carbonylation 16 in 17 patients 18 on 19 hemodialysis we also examined the effect of in vitro carbonylated albumin on mrna levels of endothelial cell adhesion molecules involved in early atherogenesis . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 examined 0 ###LEFT-WALL### 23 . 1 we 3 examined 2 also 3 examined 3 examined 5 effect 3 examined 11 on 3 examined 20 in 4 the 5 effect 5 effect 6 of 6 of 10 albumin 7 in 8 vitro 8 vitro 9 carbonylated 9 carbonylated 10 albumin 11 on 13 levels 12 mrna 13 levels 13 levels 14 of 14 of 18 molecules 15 endothelial 16 cell 16 cell 18 molecules 17 adhesion 18 molecules 18 molecules 19 involved 20 in 22 atherogenesis 21 early 22 atherogenesis methods : carbonylated proteins in uremic plasma were detected by a covalent hydrazine bait strategy and identified by combining electrophoretic separation with mass spectrometry analysis of tryptic digests . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 29 . 2 : 4 proteins 3 carbonylated 4 proteins 4 proteins 5 in 4 proteins 16 and 4 proteins 19 combining 5 in 7 plasma 6 uremic 7 plasma 8 were 9 detected 8 were 16 and 9 detected 10 by 10 by 15 strategy 11 a 12 covalent 11 a 15 strategy 12 covalent 13 hydrazine 13 hydrazine 15 strategy 14 bait 15 strategy 16 and 17 identified 16 and 18 by 19 combining 21 separation 20 electrophoretic 21 separation 21 separation 22 with 21 separation 26 of 22 with 25 analysis 23 mass 24 spectrometry 24 spectrometry 25 analysis 26 of 28 digests 27 tryptic 28 digests some plasma samples were first depleted of albumin and immunoglobulins to improve detection of lower abundance proteins . 0 ###LEFT-WALL### 3 samples 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 18 . 1 some 3 samples 2 plasma 3 samples 3 samples 9 and 4 were 6 depleted 4 were 9 and 5 first 6 depleted 6 depleted 7 of 7 of 8 albumin 9 and 10 immunoglobulins 9 and 11 to 9 and 17 proteins 11 to 12 improve 12 improve 13 detection 13 detection 14 of 14 of 16 abundance 15 lower 16 abundance the functional impact of carbonylation was assessed in human vein endothelial cells by studying models of modified human serum albumin . 0 ###LEFT-WALL### 3 impact 0 ###LEFT-WALL### 7 assessed 0 ###LEFT-WALL### 21 . 1 the 3 impact 2 functional 3 impact 3 impact 4 of 3 impact 6 was 4 of 5 carbonylation 6 was 7 assessed 7 assessed 8 in 7 assessed 13 by 8 in 12 cells 9 human 10 vein 10 vein 12 cells 11 endothelial 12 cells 13 by 14 studying 14 studying 15 models 15 models 16 of 16 of 20 albumin 17 modified 18 human 18 human 20 albumin 19 serum 20 albumin results : post - dialysis plasma carbonylated protein levels were significantly increased compared to pre - dialysis levels . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 19 . 2 : 6 plasma 2 : 18 levels 3 post 4 - 3 post 6 plasma 5 dialysis 6 plasma 6 plasma 7 carbonylated 6 plasma 9 levels 6 plasma 10 were 6 plasma 12 increased 6 plasma 13 compared 6 plasma 18 levels 8 protein 9 levels 9 levels 10 were 10 were 11 significantly 13 compared 14 to 14 to 17 dialysis 15 pre 16 - 15 pre 17 dialysis susceptibility to carbonyl formation was described on a open - platform investigation for a number of plasma proteins , albumin being the main scavenger of carbonyl reactive species . 0 ###LEFT-WALL### 1 susceptibility 0 ###LEFT-WALL### 6 described 0 ###LEFT-WALL### 29 . 1 susceptibility 2 to 1 susceptibility 5 was 2 to 4 formation 3 carbonyl 4 formation 5 was 6 described 6 described 7 on 7 on 20 albumin 8 a 20 albumin 9 open 12 investigation 9 open 20 albumin 10 - 12 investigation 11 platform 12 investigation 12 investigation 13 for 12 investigation 19 , 13 for 18 proteins 14 a 15 number 15 number 16 of 15 number 18 proteins 16 of 18 proteins 17 plasma 18 proteins 20 albumin 21 being 20 albumin 25 of 21 being 24 scavenger 22 the 24 scavenger 23 main 24 scavenger 25 of 28 species 26 carbonyl 28 species 27 reactive 28 species incubation of endothelial cells with low doses of carbonylated albumin caused a significant increase in intercellular adhesion molecule [-] 1 and vascular cell adhesion molecule - 1 mrna levels . 0 ###LEFT-WALL### 1 incubation 0 ###LEFT-WALL### 11 caused 0 ###LEFT-WALL### 26 - 0 ###LEFT-WALL### 30 . 1 incubation 2 of 1 incubation 8 of 1 incubation 11 caused 2 of 4 cells 3 endothelial 4 cells 4 cells 5 with 5 with 7 doses 6 low 7 doses 8 of 10 albumin 9 carbonylated 10 albumin 11 caused 14 increase 11 caused 15 in 12 a 13 significant 12 a 14 increase 13 significant 14 increase 15 in 21 and 16 intercellular 17 adhesion 17 adhesion 18 molecule 18 molecule 20 1 18 molecule 21 and 21 and 25 molecule 22 vascular 23 cell 23 cell 25 molecule 24 adhesion 25 molecule 26 - 29 levels 27 1 29 levels 28 mrna 29 levels conclusions : chronic uremia appears as a state of " carbonyl stress " targeting several different plasma proteins . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 4 uremia 2 : 5 appears 2 : 19 . 3 chronic 4 uremia 4 uremia 5 appears 5 appears 6 as 6 as 8 state 7 a 8 state 8 state 9 of 9 of 10 " 9 of 12 stress 11 carbonyl 12 stress 12 stress 13 " 12 stress 14 targeting 14 targeting 18 proteins 15 several 18 proteins 16 different 17 plasma 17 plasma 18 proteins carbonylated albumin displayed biological effects that may be relevant to uremic atherosclerosis . 0 ###LEFT-WALL### 2 albumin 0 ###LEFT-WALL### 3 displayed 0 ###LEFT-WALL### 13 . 1 carbonylated 2 albumin 2 albumin 3 displayed 3 displayed 5 effects 4 biological 5 effects 5 effects 6 that 5 effects 7 may 6 that 7 may 7 may 8 be 8 be 9 relevant 9 relevant 10 to 10 to 12 atherosclerosis 11 uremic 12 atherosclerosis over the past decade , use of autologous bone marrow - derived mononuclear cells ( bmcs ) has proven to be safe in phase - i/ii studies in patients with myocardial infarction ( mi ) . 0 ###LEFT-WALL### 6 use 0 ###LEFT-WALL### 19 proven 0 ###LEFT-WALL### 25 - 0 ###LEFT-WALL### 36 . 1 over 4 decade 1 over 5 , 1 over 6 use 2 the 3 past 2 the 4 decade 6 use 7 of 6 use 18 has 7 of 10 marrow 8 autologous 9 bone 9 bone 10 marrow 10 marrow 14 cells 11 - 14 cells 12 derived 14 cells 13 mononuclear 14 cells 14 cells 16 bmcs 14 cells 17 ) 15 ( 16 bmcs 16 bmcs 17 ) 18 has 19 proven 19 proven 20 to 19 proven 21 be 20 to 21 be 21 be 22 safe 22 safe 24 phase 23 in 24 phase 25 - 27 studies 26 i/ii 27 studies 27 studies 28 in 28 in 29 patients 29 patients 30 with 30 with 32 infarction 31 myocardial 32 infarction 32 infarction 34 mi 33 ( 34 mi 34 mi 35 ) taken as a whole , results support a modest yet significant improvement in cardiac function [in] cell [-] treated patients . 0 ###LEFT-WALL### 6 results 0 ###LEFT-WALL### 7 support 0 ###LEFT-WALL### 21 . 1 taken 2 as 1 taken 5 , 1 taken 6 results 2 as 4 whole 3 a 4 whole 6 results 7 support 7 support 12 improvement 7 support 13 in 8 a 12 improvement 9 modest 10 yet 10 yet 11 significant 10 yet 12 improvement 13 in 20 patients 14 cardiac 15 function 15 function 19 treated 17 cell 19 treated 19 treated 20 patients skeletal myoblasts , adipose - derived stem cells , and bone marrow - derived mesenchymal stem cells ( mscs ) have also been tested in clinical studies . 0 ###LEFT-WALL### 2 myoblasts 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 13 - 1 skeletal 2 myoblasts 2 myoblasts 4 adipose 2 myoblasts 10 and 3 , 4 adipose 4 adipose 5 - 6 derived 8 cells 6 derived 10 and 7 stem 8 cells 9 , 10 and 10 and 11 bone 11 bone 12 marrow 13 - 17 cells 13 - 24 tested 13 - 28 . 14 derived 16 stem 15 mesenchymal 16 stem 16 stem 17 cells 17 cells 19 mscs 17 cells 21 have 18 ( 19 mscs 19 mscs 20 ) 21 have 23 been 22 also 23 been 23 been 24 tested 24 tested 25 in 25 in 27 studies 26 clinical 27 studies mscs expand rapidly in vitro and have a potential for multilineage differentiation . 0 ###LEFT-WALL### 1 mscs 0 ###LEFT-WALL### 6 and 0 ###LEFT-WALL### 13 . 1 mscs 6 and 2 expand 3 rapidly 2 expand 5 vitro 2 expand 6 and 4 in 5 vitro 6 and 7 have 7 have 9 potential 8 a 9 potential 9 potential 10 for 10 for 12 differentiation 11 multilineage 12 differentiation however , their regenerative capacity decreases with aging , limiting efficacy in old patients . 0 ###LEFT-WALL### 5 capacity 0 ###LEFT-WALL### 6 decreases 1 however 2 , 1 however 5 capacity 3 their 5 capacity 4 regenerative 5 capacity 5 capacity 6 decreases 6 decreases 7 with 7 with 8 aging 8 aging 10 limiting 9 , 10 limiting 10 limiting 11 efficacy 10 limiting 12 in 10 limiting 15 . 12 in 14 patients 13 old 14 patients allogeneic mscs offer several advantages over autologous bmcs ; however , immune rejection of allogeneic cells remains a key issue . 0 ###LEFT-WALL### 2 mscs 0 ###LEFT-WALL### 3 offer 0 ###LEFT-WALL### 9 ; 0 ###LEFT-WALL### 21 . 1 allogeneic 2 mscs 2 mscs 3 offer 3 offer 5 advantages 3 offer 6 over 4 several 5 advantages 6 over 8 bmcs 7 autologous 8 bmcs 9 ; 13 rejection 9 ; 17 remains 10 however 11 , 10 however 13 rejection 12 immune 13 rejection 13 rejection 14 of 13 rejection 17 remains 14 of 16 cells 15 allogeneic 16 cells 17 remains 20 issue 18 a 20 issue 19 key 20 issue as human mscs do not express the human leukocyte antigen ( hla ) class ii under normal conditions , and [because] they modulate t - cell - mediated responses , it has been proposed that allogeneic mscs may escape immunosurveillance . 0 ###LEFT-WALL### 23 modulate 0 ###LEFT-WALL### 25 - 0 ###LEFT-WALL### 41 . 1 as 3 mscs 1 as 6 express 1 as 23 modulate 2 human 3 mscs 3 mscs 4 do 4 do 5 not 4 do 6 express 6 express 20 and 7 the 20 and 8 human 14 class 9 leukocyte 14 class 10 antigen 12 hla 10 antigen 13 ) 10 antigen 14 class 11 ( 12 hla 12 hla 13 ) 14 class 15 ii 14 class 16 under 14 class 20 and 16 under 18 conditions 17 normal 18 conditions 19 , 20 and 20 and 22 they 23 modulate 24 t 25 - 26 cell 25 - 27 - 27 - 29 responses 27 - 30 , 28 mediated 29 responses 30 , 31 it 30 , 34 proposed 31 it 32 has 32 has 33 been 33 been 34 proposed 34 proposed 35 that 35 that 37 mscs 35 that 39 escape 36 allogeneic 37 mscs 37 mscs 38 may 38 may 39 escape 39 escape 40 immunosurveillance however , recent data suggest that allogeneic mscs may switch immune states in vivo to express hla class ii , present alloantigen and induce immune rejection . 0 ###LEFT-WALL### 4 data 0 ###LEFT-WALL### 5 suggest 0 ###LEFT-WALL### 27 . 1 however 2 , 1 however 4 data 3 recent 4 data 4 data 5 suggest 5 suggest 8 mscs 5 suggest 10 switch 6 that 7 allogeneic 7 allogeneic 8 mscs 8 mscs 9 may 9 may 10 switch 10 switch 12 states 10 switch 15 to 11 immune 12 states 13 in 14 vivo 14 vivo 15 to 15 to 20 , 16 express 18 class 16 express 20 , 17 hla 18 class 18 class 19 ii 20 , 23 and 21 present 22 alloantigen 21 present 23 and 23 and 24 induce 24 induce 26 rejection 25 immune 26 rejection allogeneic mscs , unlike syngeneic ones , were eliminated from rat hearts by 5 weeks , with a loss [of] functional benefit . 0 ###LEFT-WALL### 2 mscs 0 ###LEFT-WALL### 9 eliminated 1 allogeneic 2 mscs 2 mscs 8 were 3 , 4 unlike 4 unlike 6 ones 4 unlike 7 , 4 unlike 8 were 5 syngeneic 6 ones 8 were 9 eliminated 9 eliminated 10 from 9 eliminated 13 by 10 from 12 hearts 11 rat 12 hearts 13 by 15 weeks 14 5 15 weeks 15 weeks 17 with 16 , 17 with 17 with 22 benefit 17 with 23 . 18 a 19 loss 18 a 22 benefit 19 loss 22 benefit 21 functional 22 benefit allogeneic mscs have also been tested in initial clinical studies in cardiology patients . 0 ###LEFT-WALL### 2 mscs 0 ###LEFT-WALL### 6 tested 0 ###LEFT-WALL### 14 . 1 allogeneic 2 mscs 2 mscs 3 have 3 have 5 been 4 also 5 been 5 been 6 tested 6 tested 7 in 6 tested 11 in 7 in 10 studies 8 initial 10 studies 9 clinical 10 studies 11 in 13 patients 12 cardiology 13 patients intravenous allogeneic msc infusion has proven to be safe in a phase [-] i trial in patients with acute mi . 0 ###LEFT-WALL### 4 infusion 0 ###LEFT-WALL### 6 proven 0 ###LEFT-WALL### 21 . 1 intravenous 4 infusion 2 allogeneic 4 infusion 3 msc 4 infusion 4 infusion 5 has 5 has 6 proven 6 proven 7 to 6 proven 8 be 7 to 8 be 8 be 9 safe 9 safe 10 in 9 safe 16 in 9 safe 18 with 10 in 15 trial 11 a 15 trial 12 phase 14 i 12 phase 15 trial 16 in 17 patients 18 with 20 mi 19 acute 20 mi endoventricular allogeneic msc injection has been associated with reduced adverse cardiac events in a phase [-] [ii] trial in patients with chronic heart failure . 0 ###LEFT-WALL### 3 msc 0 ###LEFT-WALL### 9 reduced 0 ###LEFT-WALL### 25 . 1 endoventricular 3 msc 2 allogeneic 3 msc 3 msc 4 injection 3 msc 8 with 3 msc 9 reduced 4 injection 5 has 5 has 6 been 6 been 7 associated 7 associated 8 with 9 reduced 12 events 9 reduced 13 in 10 adverse 12 events 11 cardiac 12 events 13 in 18 trial 14 a 18 trial 15 phase 18 trial 18 trial 19 in 19 in 20 patients 20 patients 21 with 21 with 24 failure 22 chronic 23 heart 23 heart 24 failure the long - term safety and efficacy of allogeneic mscs for cardiac repair remain to be established . 0 ###LEFT-WALL### 4 term 0 ###LEFT-WALL### 17 established 0 ###LEFT-WALL### 18 . 1 the 4 term 2 long 3 - 2 long 4 term 4 term 6 and 4 term 15 to 4 term 16 be 5 safety 6 and 6 and 7 efficacy 6 and 8 of 6 and 14 remain 8 of 10 mscs 9 allogeneic 10 mscs 10 mscs 11 for 11 for 13 repair 12 cardiac 13 repair 14 remain 15 to 16 be 17 established ongoing phase - [ii] trials are addressing these issues . 0 ###LEFT-WALL### 2 phase 0 ###LEFT-WALL### 3 - 1 ongoing 2 phase 3 - 5 trials 3 - 6 are 3 - 10 . 5 trials 6 are 6 are 7 addressing 7 addressing 9 issues 8 these 9 issues ageing shows a high interindividual and intraindividual variability . 0 ###LEFT-WALL### 1 ageing 0 ###LEFT-WALL### 2 shows 0 ###LEFT-WALL### 9 . 1 ageing 2 shows 2 shows 8 variability 3 a 4 high 3 a 8 variability 4 high 8 variability 5 interindividual 6 and 6 and 7 intraindividual 6 and 8 variability subclinical and clinical cardiovascular diseases accelerate the ageing process in part and [in] total . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 6 accelerate 0 ###LEFT-WALL### 15 . 1 subclinical 2 and 2 and 5 diseases 2 and 6 accelerate 3 clinical 5 diseases 4 cardiovascular 5 diseases 6 accelerate 9 process 6 accelerate 10 in 7 the 9 process 8 ageing 9 process 10 in 12 and 11 part 12 and 12 and 14 total this leads to the idea that ageing is a result of a chronic inflammation process and to the term " inflammageing " . 0 ###LEFT-WALL### 1 this 0 ###LEFT-WALL### 2 leads 0 ###LEFT-WALL### 23 . 1 this 2 leads 2 leads 16 and 3 to 5 idea 3 to 16 and 4 the 5 idea 5 idea 6 that 6 that 7 ageing 6 that 8 is 7 ageing 8 is 8 is 10 result 9 a 10 result 10 result 11 of 11 of 15 process 12 a 13 chronic 12 a 15 process 13 chronic 14 inflammation 14 inflammation 15 process 16 and 17 to 17 to 21 inflammageing 18 the 21 inflammageing 19 term 20 " 19 term 21 inflammageing 21 inflammageing 22 " a variety [of] biomarkers [(] e.g . c - reactive protein , interleukin - 6 , tumor necrosis factor alpha , fibrinogen , albumin and serum amyloid a ) are described in this context . 0 ###LEFT-WALL### 2 variety 0 ###LEFT-WALL### 4 biomarkers 0 ###LEFT-WALL### 7 . 1 a 2 variety 2 variety 4 biomarkers 4 biomarkers 6 e.g 7 . 8 c 7 . 9 - 7 . 12 , 8 c 9 - 9 - 11 protein 10 reactive 11 protein 12 , 13 interleukin 12 , 14 - 14 - 15 6 14 - 31 described 14 - 35 . 15 6 20 alpha 15 6 25 and 15 6 30 are 16 , 20 alpha 17 tumor 18 necrosis 18 necrosis 20 alpha 19 factor 20 alpha 20 alpha 21 , 21 , 25 and 22 fibrinogen 23 , 23 , 24 albumin 23 , 25 and 25 and 27 amyloid 25 and 29 ) 26 serum 27 amyloid 27 amyloid 28 a 30 are 31 described 31 described 32 in 32 in 34 context 33 this 34 context furthermore there is a relationship to changes in the immune system across the lifespan ( immunosenescence ) , viral infections , the occurrence of markers of oxidative stress and genetic changes . 0 ###LEFT-WALL### 2 there 0 ###LEFT-WALL### 3 is 0 ###LEFT-WALL### 21 , 0 ###LEFT-WALL### 32 . 1 furthermore 2 there 2 there 3 is 3 is 5 relationship 3 is 8 in 3 is 12 across 4 a 5 relationship 5 relationship 6 to 6 to 7 changes 8 in 11 system 9 the 11 system 10 immune 11 system 12 across 20 infections 13 the 20 infections 14 lifespan 16 immunosenescence 14 lifespan 18 , 14 lifespan 20 infections 15 ( 16 immunosenescence 16 immunosenescence 17 ) 19 viral 20 infections 21 , 29 and 22 the 23 occurrence 23 occurrence 24 of 23 occurrence 29 and 24 of 25 markers 25 markers 26 of 26 of 28 stress 27 oxidative 28 stress 29 and 31 changes 30 genetic 31 changes at this point in time the role for determining ageing and its use as a prognostic tool seems to be impossible . 0 ###LEFT-WALL### 7 role 0 ###LEFT-WALL### 18 seems 0 ###LEFT-WALL### 22 . 1 at 3 point 1 at 7 role 2 this 3 point 3 point 4 in 4 in 5 time 6 the 7 role 7 role 8 for 7 role 18 seems 8 for 9 determining 9 determining 11 and 9 determining 14 as 10 ageing 11 and 11 and 13 use 12 its 13 use 14 as 17 tool 15 a 16 prognostic 15 a 17 tool 16 prognostic 17 tool 18 seems 19 to 18 seems 20 be 19 to 20 be 20 be 21 impossible whether inflammageing is a valid model for describing the ageing process or is the consequence of other mechanisms needs further discussion . 0 ###LEFT-WALL### 19 needs 0 ###LEFT-WALL### 20 further 0 ###LEFT-WALL### 22 . 1 whether 2 inflammageing 1 whether 12 or 1 whether 19 needs 2 inflammageing 12 or 3 is 6 model 3 is 12 or 4 a 5 valid 4 a 6 model 5 valid 6 model 6 model 7 for 7 for 8 describing 8 describing 11 process 9 the 11 process 10 ageing 11 process 12 or 13 is 13 is 15 consequence 14 the 15 consequence 15 consequence 16 of 16 of 18 mechanisms 17 other 18 mechanisms 19 needs 20 further 20 further 21 discussion age impacts multiple neural measures and these changes do not always directly translate into alterations in clinical and cognitive measures . 0 ###LEFT-WALL### 1 age 0 ###LEFT-WALL### 2 impacts 0 ###LEFT-WALL### 6 and 0 ###LEFT-WALL### 21 . 1 age 2 impacts 2 impacts 5 measures 3 multiple 5 measures 4 neural 5 measures 6 and 8 changes 6 and 13 translate 7 these 8 changes 8 changes 9 do 9 do 10 not 9 do 13 translate 11 always 13 translate 12 directly 13 translate 13 translate 14 into 13 translate 16 in 14 into 15 alterations 16 in 20 measures 17 clinical 18 and 18 and 19 cognitive 18 and 20 measures this partial protection from the deleterious effects of age in some individuals is referred to as cognitive reserve ( cr ) and [although] linked to variations in intelligence and life experiences , its mechanism is still unclear . 0 ###LEFT-WALL### 3 protection 0 ###LEFT-WALL### 22 and 0 ###LEFT-WALL### 32 , 0 ###LEFT-WALL### 38 . 1 this 3 protection 2 partial 3 protection 3 protection 4 from 3 protection 8 of 3 protection 22 and 4 from 7 effects 5 the 7 effects 6 deleterious 7 effects 8 of 9 age 9 age 10 in 10 in 12 individuals 11 some 12 individuals 13 is 14 referred 13 is 22 and 14 referred 15 to 15 to 18 reserve 16 as 17 cognitive 17 cognitive 18 reserve 18 reserve 20 cr 19 ( 20 cr 20 cr 21 ) 22 and 24 linked 22 and 25 to 22 and 31 experiences 25 to 29 and 26 variations 27 in 26 variations 29 and 27 in 28 intelligence 29 and 30 life 32 , 34 mechanism 32 , 35 is 33 its 34 mechanism 34 mechanism 35 is 35 is 36 still 35 is 37 unclear within the framework of a theoretical model we tested two potential mechanistic roles of cr to maintain task performance , neural reserve and neural compensation , in young and older adults using functional and structural mri . 0 ###LEFT-WALL### 8 we 0 ###LEFT-WALL### 17 maintain 0 ###LEFT-WALL### 37 . 1 within 3 framework 1 within 8 we 2 the 3 framework 3 framework 4 of 4 of 7 model 5 a 6 theoretical 5 a 7 model 6 theoretical 7 model 8 we 9 tested 9 tested 13 roles 9 tested 16 to 10 two 13 roles 11 potential 13 roles 12 mechanistic 13 roles 13 roles 14 of 14 of 15 cr 16 to 17 maintain 17 maintain 23 and 17 maintain 32 using 18 task 19 performance 19 performance 20 , 20 , 22 reserve 20 , 23 and 21 neural 22 reserve 23 and 25 compensation 23 and 26 , 23 and 27 in 24 neural 25 compensation 27 in 31 adults 28 young 29 and 29 and 30 older 29 and 31 adults 32 using 36 mri 33 functional 34 and 34 and 35 structural 34 and 36 mri neural reserve refers to increased efficiency [and/or] capacity of existing functional neural resources . 0 ###LEFT-WALL### 2 reserve 0 ###LEFT-WALL### 3 refers 0 ###LEFT-WALL### 14 . 1 neural 2 reserve 2 reserve 3 refers 3 refers 4 to 4 to 8 capacity 5 increased 6 efficiency 6 efficiency 8 capacity 8 capacity 9 of 9 of 13 resources 10 existing 13 resources 11 functional 13 resources 12 neural 13 resources neural compensation refers to the increased ability to recruit new , additional functional resources . 0 ###LEFT-WALL### 2 compensation 0 ###LEFT-WALL### 3 refers 0 ###LEFT-WALL### 15 . 1 neural 2 compensation 2 compensation 3 refers 3 refers 4 to 4 to 7 ability 5 the 7 ability 6 increased 7 ability 7 ability 8 to 7 ability 9 recruit 8 to 9 recruit 9 recruit 14 resources 10 new 11 , 10 new 14 resources 12 additional 14 resources 13 functional 14 resources using structural and functional measures and task performance , the roles of cr were tested using path analysis . 0 ###LEFT-WALL### 11 roles 0 ###LEFT-WALL### 15 tested 0 ###LEFT-WALL### 19 . 1 using 6 and 1 using 9 , 1 using 11 roles 2 structural 3 and 3 and 4 functional 3 and 5 measures 5 measures 6 and 6 and 8 performance 7 task 8 performance 10 the 11 roles 11 roles 12 of 11 roles 14 were 12 of 13 cr 14 were 15 tested 15 tested 16 using 16 using 18 analysis 17 path 18 analysis results supported both mechanistic theories of cr and the use of our general theoretical model . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 supported 0 ###LEFT-WALL### 16 . 1 results 2 supported 2 supported 5 theories 3 both 5 theories 4 mechanistic 5 theories 5 theories 6 of 6 of 8 and 7 cr 8 and 8 and 10 use 8 and 11 of 9 the 10 use 11 of 15 model 12 our 15 model 13 general 15 model 14 theoretical 15 model it has been suggested that inflammation is involved in alzheimer [disease] ( ad ) pathogenesis . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 4 suggested 0 ###LEFT-WALL### 16 . 1 it 2 has 2 has 3 been 3 been 4 suggested 4 suggested 5 that 5 that 6 inflammation 5 that 8 involved 6 inflammation 7 is 7 is 8 involved 8 involved 9 in 9 in 15 pathogenesis 10 alzheimer 13 ad 12 ( 13 ad 13 ad 14 ) 13 ad 15 pathogenesis the aim of this study is to evaluate the association between inflammatory aspects of diet [and] incident ad risk . 0 ###LEFT-WALL### 2 aim 0 ###LEFT-WALL### 20 . 1 the 2 aim 2 aim 3 of 2 aim 6 is 3 of 5 study 4 this 5 study 6 is 7 to 6 is 8 evaluate 7 to 8 evaluate 8 evaluate 10 association 8 evaluate 11 between 9 the 10 association 11 between 13 aspects 12 inflammatory 13 aspects 13 aspects 14 of 14 of 19 risk 15 diet 19 risk 17 incident 19 risk 18 ad 19 risk about 2258 [nondemented] elderly ( age ≥ 65 ) in new york who provided dietary information at baseline were followed - up prospectively for ad development . 0 ###LEFT-WALL### 12 york 0 ###LEFT-WALL### 21 - 1 about 10 in 1 about 12 york 2 2258 10 in 4 elderly 7 ≥ 4 elderly 10 in 5 ( 7 ≥ 6 age 7 ≥ 7 ≥ 8 65 7 ≥ 9 ) 11 new 12 york 12 york 13 who 12 york 14 provided 12 york 19 were 13 who 14 provided 14 provided 16 information 15 dietary 16 information 16 information 17 at 17 at 18 baseline 19 were 20 followed 21 - 22 up 21 - 27 . 22 up 23 prospectively 22 up 24 for 22 up 26 development 24 for 25 ad the tifr was not associated with serum hscrp level . 0 ###LEFT-WALL### 2 tifr 0 ###LEFT-WALL### 3 was 0 ###LEFT-WALL### 10 . 1 the 2 tifr 2 tifr 3 was 3 was 4 not 3 was 6 with 4 not 5 associated 6 with 9 level 7 serum 9 level 8 hscrp 9 level after an average of 4.0 years of [follow] - up , 262 participants developed incident ad . 0 ###LEFT-WALL### 13 participants 0 ###LEFT-WALL### 14 developed 0 ###LEFT-WALL### 17 . 1 after 3 average 1 after 11 , 1 after 13 participants 2 an 3 average 3 average 4 of 4 of 6 years 5 4.0 6 years 6 years 7 of 7 of 10 up 9 - 10 up 12 262 13 participants 13 participants 14 developed 14 developed 16 ad 15 incident 16 ad we conclude that tifr might not be a biologically relevant measure of the inflammatory impact of the diet . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 conclude 0 ###LEFT-WALL### 19 . 1 we 2 conclude 2 conclude 3 that 3 that 4 tifr 3 that 7 be 4 tifr 5 might 5 might 6 not 5 might 7 be 7 be 15 impact 8 a 9 biologically 8 a 11 measure 9 biologically 10 relevant 10 relevant 11 measure 11 measure 12 of 11 measure 15 impact 12 of 15 impact 13 the 15 impact 14 inflammatory 15 impact 15 impact 16 of 16 of 18 diet 17 the 18 diet in addition , although it remains possible that tifr might be related with some other aspects of inflammation not captured by hscrp , lack of [association] with ad risk suggests its limited clinical utility . 0 ###LEFT-WALL### 9 tifr 0 ###LEFT-WALL### 12 related 0 ###LEFT-WALL### 19 not 0 ###LEFT-WALL### 35 . 1 in 2 addition 1 in 3 , 1 in 9 tifr 4 although 5 it 4 although 6 remains 4 although 9 tifr 5 it 6 remains 6 remains 7 possible 8 that 9 tifr 9 tifr 10 might 10 might 11 be 11 be 12 related 12 related 13 with 13 with 16 aspects 14 some 15 other 15 other 16 aspects 16 aspects 17 of 17 of 18 inflammation 19 not 24 lack 19 not 30 suggests 20 captured 21 by 20 captured 23 , 20 captured 24 lack 21 by 22 hscrp 24 lack 25 of 24 lack 30 suggests 25 of 27 with 27 with 29 risk 28 ad 29 risk 30 suggests 34 utility 31 its 34 utility 32 limited 34 utility 33 clinical 34 utility the neuropsychological battery from the national alzheimer 's disease coordinating center is designed to provide a sensitive assessment of mild cognitive disorders for multicenter investigations . 0 ###LEFT-WALL### 3 battery 0 ###LEFT-WALL### 13 designed 0 ###LEFT-WALL### 26 . 1 the 3 battery 2 neuropsychological 3 battery 3 battery 4 from 3 battery 12 is 4 from 11 center 5 the 7 alzheimer 6 national 7 alzheimer 7 alzheimer 8 's 8 's 11 center 9 disease 10 coordinating 10 coordinating 11 center 12 is 13 designed 13 designed 14 to 13 designed 15 provide 14 to 15 provide 15 provide 18 assessment 16 a 17 sensitive 16 a 18 assessment 17 sensitive 18 assessment 18 assessment 19 of 18 assessment 23 for 19 of 22 disorders 20 mild 22 disorders 21 cognitive 22 disorders 23 for 25 investigations 24 multicenter 25 investigations comprising 8 common neuropsychological tests ( 12 measures ) , the battery assesses cognitive domains affected early in the course of alzheimer disease . 0 ###LEFT-WALL### 12 battery 0 ###LEFT-WALL### 13 assesses 0 ###LEFT-WALL### 24 . 1 comprising 5 tests 1 comprising 10 , 1 comprising 12 battery 2 8 5 tests 3 common 5 tests 4 neuropsychological 5 tests 5 tests 8 measures 6 ( 8 measures 7 12 8 measures 8 measures 9 ) 11 the 12 battery 12 battery 13 assesses 13 assesses 15 domains 14 cognitive 15 domains 15 domains 16 affected 16 affected 17 early 17 early 18 in 18 in 20 course 19 the 20 course 20 course 21 of 21 of 23 disease 22 alzheimer 23 disease we examined the factor structure of the battery across levels of cognition [ normal , mild cognitive impairment , dementia ] based on clinical dementia rating scores to determine cognitive domains tapped by the battery . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 examined 0 ###LEFT-WALL### 36 . 1 we 2 examined 2 examined 5 structure 2 examined 28 to 3 the 5 structure 4 factor 5 structure 5 structure 6 of 6 of 8 battery 7 the 8 battery 8 battery 9 across 8 battery 11 of 8 battery 22 based 9 across 10 levels 11 of 12 cognition 12 cognition 18 impairment 12 cognition 20 dementia 13 [ 18 impairment 14 normal 15 , 14 normal 18 impairment 16 mild 18 impairment 17 cognitive 18 impairment 18 impairment 19 , 19 , 20 dementia 20 dementia 21 ] 22 based 23 on 23 on 25 dementia 24 clinical 25 dementia 25 dementia 26 rating 25 dementia 27 scores 26 rating 27 scores 28 to 29 determine 29 determine 31 domains 29 determine 33 by 30 cognitive 31 domains 31 domains 32 tapped 33 by 35 battery 34 the 35 battery using data pooled from 29 alzheimer 's disease centers funded by national institute on aging , exploratory factor analysis was used to derive a general model using half of the sample ; 4 factors representing memory , attention , executive function , and language were identified . 0 ###LEFT-WALL### 19 analysis 0 ###LEFT-WALL### 21 used 0 ###LEFT-WALL### 32 ; 0 ###LEFT-WALL### 47 . 1 using 2 data 1 using 11 by 1 using 16 , 1 using 19 analysis 2 data 3 pooled 2 data 9 centers 2 data 10 funded 3 pooled 4 from 4 from 5 29 6 alzheimer 7 's 7 's 9 centers 8 disease 9 centers 9 centers 10 funded 11 by 13 institute 12 national 13 institute 13 institute 14 on 14 on 15 aging 17 exploratory 19 analysis 18 factor 19 analysis 19 analysis 20 was 20 was 21 used 21 used 22 to 21 used 23 derive 22 to 23 derive 23 derive 26 model 23 derive 27 using 24 a 26 model 25 general 26 model 27 using 28 half 28 half 29 of 29 of 31 sample 30 the 31 sample 32 ; 34 factors 32 ; 46 identified 33 4 34 factors 34 factors 35 representing 34 factors 45 were 35 representing 43 and 36 memory 37 , 37 , 38 attention 37 , 39 , 39 , 41 function 39 , 43 and 40 executive 41 function 42 , 43 and 43 and 44 language 45 were 46 identified confirmatory factor analysis was used on the second half of the sample to evaluate invariance between groups and within groups over 1 year . 0 ###LEFT-WALL### 3 analysis 0 ###LEFT-WALL### 5 used 0 ###LEFT-WALL### 24 . 1 confirmatory 3 analysis 2 factor 3 analysis 3 analysis 4 was 4 was 5 used 5 used 6 on 5 used 13 to 5 used 14 evaluate 6 on 9 half 7 the 8 second 7 the 9 half 9 half 10 of 10 of 12 sample 11 the 12 sample 13 to 14 evaluate 14 evaluate 15 invariance 14 evaluate 21 over 15 invariance 18 and 16 between 17 groups 16 between 18 and 18 and 19 within 19 within 20 groups 21 over 23 year 22 1 23 year factorial invariance testing included systematic addition of constraints and comparisons of nested models . 0 ###LEFT-WALL### 1 factorial 0 ###LEFT-WALL### 12 nested 0 ###LEFT-WALL### 14 . 1 factorial 3 testing 1 factorial 11 of 1 factorial 12 nested 2 invariance 3 testing 3 testing 4 included 4 included 6 addition 5 systematic 6 addition 6 addition 7 of 7 of 9 and 8 constraints 9 and 9 and 10 comparisons 9 and 11 of 12 nested 13 models the general confirmatory factor analysis model had a good fit . 0 ###LEFT-WALL### 6 model 0 ###LEFT-WALL### 7 had 0 ###LEFT-WALL### 11 . 1 the 6 model 2 general 3 confirmatory 3 confirmatory 6 model 4 factor 6 model 5 analysis 6 model 6 model 7 had 7 had 10 fit 8 a 9 good 8 a 10 fit 9 good 10 fit as constraints were added , model fit [deteriorated] slightly . 0 ###LEFT-WALL### 7 fit 0 ###LEFT-WALL### 10 . 1 as 2 constraints 1 as 5 , 1 as 7 fit 2 constraints 3 were 3 were 5 , 4 added 5 , 5 , 6 model 7 fit 9 slightly comparisons within groups showed stability over 1 year . 0 ###LEFT-WALL### 1 comparisons 0 ###LEFT-WALL### 4 showed 0 ###LEFT-WALL### 9 . 1 comparisons 2 within 1 comparisons 4 showed 2 within 3 groups 4 showed 5 stability 4 showed 6 over 6 over 8 year 7 1 8 year in a range of cognition from normal to dementia , factor structures and factor loadings will vary little . 0 ###LEFT-WALL### 15 loadings 0 ###LEFT-WALL### 17 vary 0 ###LEFT-WALL### 19 . 1 in 3 range 1 in 15 loadings 2 a 3 range 3 range 4 of 4 of 5 cognition 5 cognition 6 from 6 from 13 and 7 normal 8 to 7 normal 10 , 8 to 9 dementia 10 , 12 structures 10 , 13 and 11 factor 12 structures 13 and 14 factor 15 loadings 16 will 16 will 17 vary 17 vary 18 little further work [is] needed to determine whether domains become more or less distinct in severely cognitively compromised individuals . 0 ###LEFT-WALL### 2 work 0 ###LEFT-WALL### 17 compromised 0 ###LEFT-WALL### 19 . 1 further 2 work 2 work 4 needed 2 work 5 to 2 work 14 in 2 work 17 compromised 5 to 6 determine 6 determine 7 whether 6 determine 14 in 7 whether 8 domains 7 whether 9 become 8 domains 9 become 9 become 11 or 9 become 13 distinct 10 more 11 or 11 or 12 less 15 severely 17 compromised 16 cognitively 17 compromised 17 compromised 18 individuals objective : this study tested a structural model and examined the relationships between age , suicidal ideation , and scores on the 5 - item brief symptom rating scale ( bsrs - 5 ) , the 15 - item geriatric depression scale ( gds - 15 ) , and the medical outcome study short form - 12 ( mos sf - 12 ) in a sample of veterans ' home residents . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 72 . 1 objective 2 : 2 : 4 study 3 this 4 study 4 study 9 and 5 tested 8 model 5 tested 9 and 6 a 7 structural 6 a 8 model 7 structural 8 model 9 and 10 examined 9 and 13 between 9 and 64 in 10 examined 12 relationships 11 the 12 relationships 13 between 19 and 14 age 15 , 15 , 17 ideation 15 , 19 and 16 suicidal 17 ideation 18 , 19 and 19 and 20 scores 19 and 21 on 19 and 31 bsrs 21 on 23 5 22 the 23 5 24 - 31 bsrs 25 item 31 bsrs 26 brief 27 symptom 27 symptom 28 rating 28 rating 29 scale 29 scale 31 bsrs 30 ( 31 bsrs 31 bsrs 33 5 31 bsrs 37 15 31 bsrs 42 scale 31 bsrs 63 ) 32 - 33 5 33 5 34 ) 35 , 37 15 36 the 37 15 37 15 38 - 38 - 42 scale 39 item 42 scale 40 geriatric 41 depression 41 depression 42 scale 42 scale 49 and 42 scale 57 12 42 scale 63 ) 43 ( 49 and 44 gds 46 15 44 gds 49 and 45 - 46 15 46 15 47 ) 48 , 49 and 49 and 55 form 49 and 56 - 50 the 55 form 51 medical 52 outcome 52 outcome 53 study 53 study 54 short 54 short 55 form 56 - 57 12 57 12 60 sf 57 12 63 ) 58 ( 60 sf 59 mos 60 sf 60 sf 62 12 60 sf 63 ) 61 - 62 12 62 12 63 ) 64 in 66 sample 65 a 66 sample 66 sample 67 of 67 of 71 residents 68 veterans 69 ' 69 ' 71 residents 70 home 71 residents methods : of the 266 individuals recruited , 226 completed the questionnaires , resulting in a response rate of 84.9 % . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 8 , 1 methods 2 : 2 : 3 of 3 of 6 individuals 4 the 5 266 5 266 6 individuals 6 individuals 7 recruited 8 , 9 226 8 , 10 completed 9 226 10 completed 10 completed 12 questionnaires 10 completed 14 resulting 11 the 12 questionnaires 13 , 14 resulting 14 resulting 15 in 14 resulting 22 . 15 in 18 rate 16 a 18 rate 17 response 18 rate 18 rate 19 of 19 of 21 % 20 84.9 21 % participants completed the bsrs - 5 , gds - 15 , mos sf - 12 , and a demographic survey . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 2 completed 0 ###LEFT-WALL### 21 . 1 participants 2 completed 2 completed 17 and 3 the 17 and 4 bsrs 6 5 4 bsrs 17 and 5 - 6 5 6 5 8 gds 6 5 16 , 7 , 8 gds 8 gds 10 15 8 gds 16 , 9 - 10 15 10 15 13 sf 10 15 15 12 10 15 16 , 11 , 13 sf 12 mos 13 sf 13 sf 14 - 14 - 15 12 15 12 16 , 16 , 17 and 17 and 20 survey 18 a 20 survey 19 demographic 20 survey analysis of moment structures , version 7.0 , was used to test the structural relationships of the model with a structural equation modeling analysis and a maximum likelihood ratio estimation . 0 ###LEFT-WALL### 1 analysis 0 ###LEFT-WALL### 10 used 0 ###LEFT-WALL### 31 . 1 analysis 2 of 1 analysis 9 was 2 of 4 structures 3 moment 4 structures 4 structures 6 version 5 , 6 version 6 version 7 7.0 6 version 8 , 9 was 10 used 10 used 11 to 10 used 12 test 11 to 12 test 12 test 15 relationships 12 test 19 with 13 the 15 relationships 14 structural 15 relationships 15 relationships 16 of 16 of 18 model 17 the 18 model 19 with 30 estimation 20 a 21 structural 20 a 22 equation 21 structural 22 equation 22 equation 23 modeling 22 equation 25 and 23 modeling 24 analysis 25 and 27 maximum 25 and 30 estimation 26 a 27 maximum 28 likelihood 30 estimation 29 ratio 30 estimation patient subitem scores , which ranked their feelings of depression , hostility , and inferiority , were summed to determine their 3 - bsrs - subitem sum scores . 0 ###LEFT-WALL### 3 scores 0 ###LEFT-WALL### 18 summed 0 ###LEFT-WALL### 29 . 1 patient 2 subitem 2 subitem 3 scores 3 scores 5 which 3 scores 14 and 3 scores 17 were 4 , 5 which 5 which 6 ranked 5 which 11 , 6 ranked 8 feelings 7 their 8 feelings 8 feelings 9 of 9 of 10 depression 11 , 14 and 12 hostility 14 and 13 , 14 and 14 and 15 inferiority 14 and 16 , 17 were 18 summed 18 summed 19 to 19 to 20 determine 20 determine 28 scores 21 their 28 scores 22 3 24 bsrs 23 - 24 bsrs 24 bsrs 25 - 24 bsrs 26 subitem 26 subitem 27 sum 27 sum 28 scores results : the measures of model fitness were as [follows] [:] goodness - [of] - fit [(] χ = 12.03 , df = 7 , p = 0.1 ) , goodness - [of] - fit index ( 0.98 ) , adjusted goodness - of [-] fit index ( 0.95 ) , comparative fit index ( 0.99 ) , parsimony ratio ( 0.47 [ )(, and root mean square error of approximation ( 0.06 ) . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 4 measures 2 : 13 - 3 the 4 measures 4 measures 5 of 4 measures 8 were 5 of 7 fitness 6 model 7 fitness 8 were 9 as 9 as 12 goodness 13 - 15 - 13 - 21 , 15 - 18 χ 16 fit 18 χ 18 χ 19 = 19 = 20 12.03 21 , 22 df 21 , 23 = 21 , 32 - 22 df 23 = 23 = 24 7 24 7 27 = 24 7 31 goodness 25 , 27 = 26 p 27 = 27 = 28 0.1 27 = 29 ) 30 , 31 goodness 31 goodness 32 - 32 - 34 - 32 - 40 , 32 - 43 - 34 - 35 fit 35 fit 36 index 36 index 38 0.98 37 ( 38 0.98 38 0.98 39 ) 40 , 42 goodness 41 adjusted 42 goodness 43 - 52 comparative 44 of 47 index 44 of 51 , 44 of 52 comparative 46 fit 47 index 47 index 49 0.95 48 ( 49 0.95 49 0.95 50 ) 52 comparative 53 fit 53 fit 54 index 54 index 56 0.99 54 index 65 and 55 ( 56 0.99 56 0.99 57 ) 58 , 65 and 59 parsimony 65 and 60 ratio 62 0.47 61 ( 62 0.47 62 0.47 64 )(, 64 )(, 65 and 65 and 69 error 65 and 70 of 65 and 75 . 66 root 69 error 67 mean 69 error 68 square 69 error 70 of 71 approximation 71 approximation 73 0.06 72 ( 73 0.06 73 0.06 74 ) all indices suggested that the final model fit the data well . 0 ###LEFT-WALL### 2 indices 0 ###LEFT-WALL### 3 suggested 0 ###LEFT-WALL### 12 . 1 all 2 indices 2 indices 3 suggested 3 suggested 4 that 4 that 7 model 4 that 8 fit 5 the 7 model 6 final 7 model 7 model 8 fit 8 fit 10 data 8 fit 11 well 9 the 10 data age [was] inversely related [to] physical component summary , which was inversely related to the 3 - bsrs - subitem sum score . 0 ###LEFT-WALL### 8 summary 0 ###LEFT-WALL### 9 , 1 age 8 summary 3 inversely 4 related 4 related 7 component 6 physical 7 component 7 component 8 summary 9 , 10 which 9 , 13 related 9 , 19 - 10 which 11 was 11 was 13 related 12 inversely 13 related 13 related 14 to 14 to 18 bsrs 15 the 18 bsrs 16 3 18 bsrs 17 - 18 bsrs 19 - 22 score 19 - 23 . 20 subitem 22 score 21 sum 22 score mental [component] [summary] was inversely related to the 3 - bsrs - subitem sum score and the gds - 15 . 0 ###LEFT-WALL### 1 mental 0 ###LEFT-WALL### 6 related 0 ###LEFT-WALL### 19 - 0 ###LEFT-WALL### 21 . 1 mental 4 was 4 was 5 inversely 4 was 6 related 6 related 7 to 7 to 16 and 8 the 15 score 9 3 11 bsrs 10 - 11 bsrs 11 bsrs 12 - 11 bsrs 15 score 13 subitem 15 score 14 sum 15 score 15 score 16 and 16 and 18 gds 17 the 18 gds 19 - 20 15 physical [component] [summary] was inversely related to the gds - 15 . 0 ###LEFT-WALL### 1 physical 0 ###LEFT-WALL### 6 related 0 ###LEFT-WALL### 10 - 0 ###LEFT-WALL### 12 . 1 physical 4 was 4 was 6 related 5 inversely 6 related 6 related 7 to 7 to 9 gds 8 the 9 gds 10 - 11 15 the 3 - bsrs - subitem sum score correlated with suicidal ideation . 0 ###LEFT-WALL### 8 score 0 ###LEFT-WALL### 9 correlated 0 ###LEFT-WALL### 13 . 1 the 8 score 2 3 4 bsrs 3 - 4 bsrs 4 bsrs 5 - 4 bsrs 8 score 6 subitem 8 score 7 sum 8 score 8 score 9 correlated 9 correlated 10 with 10 with 12 ideation 11 suicidal 12 ideation conclusions : the data reveal a significant relationship between quality of life and suicidal ideation , which may be affected more by the 3 - bsrs - subitem sum score than by the gds - 15 . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 4 data 2 : 5 reveal 2 : 16 , 2 : 37 . 3 the 4 data 4 data 5 reveal 5 reveal 8 relationship 5 reveal 9 between 6 a 7 significant 6 a 8 relationship 7 significant 8 relationship 9 between 13 and 10 quality 11 of 10 quality 13 and 11 of 12 life 13 and 15 ideation 14 suicidal 15 ideation 16 , 17 which 16 , 20 affected 16 , 35 - 17 which 18 may 18 may 19 be 19 be 20 affected 20 affected 21 more 20 affected 22 by 20 affected 31 than 22 by 30 score 23 the 30 score 24 3 26 bsrs 25 - 26 bsrs 26 bsrs 27 - 26 bsrs 28 subitem 28 subitem 30 score 29 sum 30 score 31 than 32 by 32 by 34 gds 33 the 34 gds 35 - 36 15 the proposed model has the potential to help healthcare professionals effectively design and implement their suicide prevention programs . 0 ###LEFT-WALL### 3 model 0 ###LEFT-WALL### 4 has 0 ###LEFT-WALL### 19 . 1 the 3 model 2 proposed 3 model 3 model 4 has 4 has 13 and 5 the 6 potential 6 potential 7 to 6 potential 13 and 7 to 8 help 8 help 10 professionals 8 help 12 design 9 healthcare 10 professionals 10 professionals 12 design 11 effectively 12 design 13 and 14 implement 13 and 17 prevention 13 and 18 programs 15 their 17 prevention 16 suicide 17 prevention 17 prevention 18 programs objectives : to examine alternative models of defining and characterizing successful aging . 0 ###LEFT-WALL### 1 objectives 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 13 . 2 : 3 to 2 : 4 examine 3 to 4 examine 4 examine 6 models 5 alternative 6 models 6 models 7 of 7 of 9 and 8 defining 9 and 9 and 12 aging 10 characterizing 12 aging 11 successful 12 aging design : a retrospective cohort study . 0 ###LEFT-WALL### 1 design 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 7 . 1 design 2 : 2 : 6 study 3 a 4 retrospective 3 a 6 study 4 retrospective 5 cohort 5 cohort 6 study setting : olmsted county , mn . 0 ###LEFT-WALL### 1 setting 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 5 , 0 ###LEFT-WALL### 7 . 1 setting 2 : 2 : 4 county 3 olmsted 4 county 5 , 6 mn participants : five hundred sixty community [-] dwelling nondemented adults , aged 65 years and older . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 2 : 1 participants 2 : 2 : 10 adults 3 five 4 hundred 4 hundred 5 sixty 5 sixty 10 adults 6 community 9 nondemented 8 dwelling 9 nondemented 9 nondemented 10 adults 10 adults 12 aged 11 , 12 aged 12 aged 15 and 12 aged 17 . 13 65 14 years 14 years 15 and 15 and 16 older measurements : three models were developed . 0 ###LEFT-WALL### 1 measurements 0 ###LEFT-WALL### 2 : 2 : 4 models 2 : 6 developed 2 : 7 . 3 three 4 models 4 models 5 were 5 were 6 developed each model examined subtests in four cognitive domains : memory , attention/executive function , language , and visuospatial skills . 0 ###LEFT-WALL### 2 model 0 ###LEFT-WALL### 3 examined 0 ###LEFT-WALL### 9 : 1 each 2 model 2 model 3 examined 3 examined 4 subtests 3 examined 5 in 5 in 8 domains 6 four 8 domains 7 cognitive 8 domains 9 : 17 and 9 : 20 . 10 memory 11 , 11 , 13 function 11 , 14 , 12 attention/executive 13 function 14 , 15 language 14 , 17 and 16 , 17 and 17 and 19 skills 18 visuospatial 19 skills a composite domain score was generated for each of the four domains . 0 ###LEFT-WALL### 4 score 0 ###LEFT-WALL### 6 generated 0 ###LEFT-WALL### 13 . 1 a 2 composite 1 a 4 score 2 composite 3 domain 3 domain 4 score 4 score 5 was 5 was 6 generated 6 generated 7 for 7 for 12 domains 8 each 9 of 8 each 12 domains 9 of 12 domains 10 the 11 four 11 four 12 domains in model 1 , a global [z] score was further generated from the four cognitive domains , and subjects with mean global [z] score in the top 10 % were classified as " successful agers , " [whereas] those in the remaining 90 % were classified as " typical agers . " 0 ###LEFT-WALL### 8 score 0 ###LEFT-WALL### 11 generated 1 in 2 model 1 in 4 , 1 in 8 score 2 model 3 1 5 a 6 global 5 a 8 score 6 global 8 score 8 score 9 was 9 was 10 further 9 was 11 generated 11 generated 12 from 12 from 24 score 13 the 24 score 14 four 24 score 15 cognitive 16 domains 16 domains 18 and 17 , 18 and 18 and 19 subjects 18 and 20 with 18 and 24 score 20 with 21 mean 22 global 24 score 24 score 25 in 24 score 31 classified 25 in 27 top 26 the 27 top 27 top 29 % 27 top 30 were 28 10 29 % 29 % 30 were 31 classified 32 as 32 as 33 " 32 as 35 agers 34 successful 35 agers 35 agers 39 those 36 , 37 " 36 , 39 those 39 those 40 in 39 those 44 % 39 those 45 were 39 those 46 classified 39 those 51 . 40 in 42 remaining 41 the 42 remaining 43 90 44 % 44 % 45 were 46 classified 47 as 47 as 48 " 47 as 50 agers 49 typical 50 agers 51 . 52 " in model 2 , subjects with all four domain scores above the 50th percentile were classified as " successful agers . " 0 ###LEFT-WALL### 5 subjects 0 ###LEFT-WALL### 15 were 0 ###LEFT-WALL### 21 . 1 in 2 model 1 in 4 , 1 in 5 subjects 2 model 3 2 5 subjects 6 with 5 subjects 15 were 6 with 10 scores 7 all 8 four 8 four 10 scores 9 domain 10 scores 10 scores 11 above 11 above 14 percentile 12 the 14 percentile 13 50th 14 percentile 15 were 16 classified 16 classified 17 as 17 as 18 " 17 as 20 agers 19 successful 20 agers 21 . 22 " in model 3 , a primary neuropsychological variable was selected from each domain , and subjects whose score remained above - 1 standard deviation compared with norms for young adults were labeled successful agers . 0 ###LEFT-WALL### 8 variable 0 ###LEFT-WALL### 15 and 0 ###LEFT-WALL### 35 . 1 in 2 model 1 in 4 , 1 in 8 variable 2 model 3 3 5 a 6 primary 5 a 8 variable 6 primary 8 variable 7 neuropsychological 8 variable 8 variable 9 was 9 was 10 selected 10 selected 11 from 11 from 13 domain 12 each 13 domain 14 , 15 and 15 and 16 subjects 15 and 31 were 16 subjects 17 whose 16 subjects 25 compared 16 subjects 26 with 16 subjects 31 were 17 whose 18 score 18 score 19 remained 19 remained 20 above 20 above 24 deviation 21 - 22 1 22 1 24 deviation 23 standard 24 deviation 26 with 27 norms 27 norms 28 for 28 for 30 adults 29 young 30 adults 31 were 34 agers 32 labeled 34 agers 33 successful 34 agers validation tests were conducted to determine the ability of each model to predict survival and conversion to mild cognitive impairment ( mci ) . 0 ###LEFT-WALL### 2 tests 0 ###LEFT-WALL### 4 conducted 0 ###LEFT-WALL### 24 . 1 validation 2 tests 2 tests 3 were 3 were 4 conducted 4 conducted 5 to 4 conducted 12 to 5 to 6 determine 6 determine 8 ability 7 the 8 ability 8 ability 9 of 9 of 11 model 10 each 11 model 12 to 13 predict 13 predict 15 and 13 predict 17 to 14 survival 15 and 15 and 16 conversion 17 to 20 impairment 18 mild 20 impairment 19 cognitive 20 impairment 20 impairment 22 mci 21 ( 22 mci 22 mci 23 ) results : model 1 showed 65 % lower mortality in successful agers compared with typical agers and also a 25 % lower conversion rate to mci . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 3 model 2 : 5 showed 2 : 27 . 3 model 4 1 3 model 5 showed 5 showed 7 % 5 showed 8 lower 6 65 7 % 7 % 8 lower 8 lower 17 and 8 lower 25 to 9 mortality 10 in 9 mortality 17 and 10 in 12 agers 11 successful 12 agers 12 agers 13 compared 12 agers 14 with 14 with 16 agers 15 typical 16 agers 17 and 18 also 17 and 24 rate 19 a 24 rate 20 25 21 % 21 % 24 rate 22 lower 23 conversion 23 conversion 24 rate 25 to 26 mci objective : to examine the association [of] cognitive function with the risk of incident mobility impairments and the rate of declining mobility in older adults . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 2 : 3 to 2 : 4 examine 2 : 26 . 3 to 4 examine 4 examine 9 function 4 examine 10 with 4 examine 23 in 5 the 9 function 6 association 9 function 8 cognitive 9 function 10 with 17 and 11 the 12 risk 12 risk 13 of 12 risk 17 and 13 of 16 impairments 14 incident 16 impairments 15 mobility 16 impairments 17 and 19 rate 17 and 20 of 18 the 19 rate 20 of 21 declining 21 declining 22 mobility 23 in 25 adults 24 older 25 adults design : prospective , observational cohort study . 0 ###LEFT-WALL### 1 design 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 8 . 1 design 2 : 2 : 7 study 3 prospective 4 , 3 prospective 6 cohort 5 observational 6 cohort 6 cohort 7 study setting : retirement communities across metropolitan chicago . 0 ###LEFT-WALL### 1 setting 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 8 . 1 setting 2 : 2 : 4 communities 3 retirement 4 communities 4 communities 5 across 5 across 7 chicago 6 metropolitan 7 chicago participants : a total of 1,154 ambulatory elders from two longitudinal studies without baseline clinical dementia or history of stroke [or] parkinson disease . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 24 . 2 : 4 total 3 a 4 total 4 total 5 of 5 of 8 elders 6 1,154 8 elders 7 ambulatory 8 elders 8 elders 9 from 9 from 12 studies 10 two 12 studies 11 longitudinal 12 studies 12 studies 13 without 13 without 17 or 14 baseline 16 dementia 15 clinical 16 dementia 16 dementia 17 or 17 or 18 history 17 or 19 of 19 of 23 disease 20 stroke 23 disease 22 parkinson 23 disease measurements : all participants underwent baseline cognitive testing and annual mobility examinations . 0 ###LEFT-WALL### 1 measurements 0 ###LEFT-WALL### 2 : 2 : 4 participants 2 : 5 underwent 2 : 13 . 3 all 4 participants 4 participants 5 underwent 5 underwent 9 and 6 baseline 8 testing 7 cognitive 8 testing 8 testing 9 and 9 and 12 examinations 10 annual 11 mobility 11 mobility 12 examinations mobility impairments were based on annual timed [walking] performance . 0 ###LEFT-WALL### 2 impairments 0 ###LEFT-WALL### 4 based 0 ###LEFT-WALL### 10 . 1 mobility 2 impairments 2 impairments 3 were 3 were 4 based 4 based 5 on 5 on 9 performance 6 annual 7 timed 7 timed 9 performance a composite mobility measure , which summarized gait [and] balance measures , was used to examine the annual rate of mobility change . 0 ###LEFT-WALL### 4 measure 0 ###LEFT-WALL### 5 , 0 ###LEFT-WALL### 14 used 0 ###LEFT-WALL### 23 . 1 a 2 composite 1 a 4 measure 2 composite 3 mobility 3 mobility 4 measure 5 , 6 which 5 , 12 , 6 which 12 , 7 summarized 11 measures 7 summarized 12 , 8 gait 11 measures 10 balance 11 measures 12 , 13 was 13 was 14 used 14 used 15 to 14 used 16 examine 15 to 16 examine 16 examine 19 rate 17 the 19 rate 18 annual 19 rate 19 rate 20 of 20 of 22 change 21 mobility 22 change results : during [follow] - up of 4.5 years , 423 of 836 ( 50.6 % ) participants developed impaired mobility . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 18 participants 2 : 20 impaired 2 : 22 . 3 during 6 up 3 during 18 participants 5 - 6 up 7 of 9 years 7 of 17 ) 7 of 18 participants 8 4.5 9 years 9 years 11 423 10 , 11 423 11 423 12 of 11 423 17 ) 12 of 13 836 13 836 16 % 14 ( 16 % 15 50.6 16 % 16 % 17 ) 18 participants 19 developed 18 participants 20 impaired 20 impaired 21 mobility these results did not vary by sex or race and were unchanged in analyses controlling for body mass index [,] physical activity , vascular diseases , and risk factors . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 8 or 0 ###LEFT-WALL### 30 . 1 these 2 results 2 results 3 did 3 did 4 not 3 did 8 or 5 vary 6 by 5 vary 8 or 6 by 7 sex 8 or 10 and 9 race 10 and 10 and 11 were 11 were 12 unchanged 12 unchanged 13 in 13 in 14 analyses 14 analyses 15 controlling 15 controlling 16 for 15 controlling 29 factors 16 for 27 and 17 body 18 mass 18 mass 22 activity 19 index 22 activity 21 physical 22 activity 22 activity 23 , 23 , 25 diseases 23 , 27 and 24 vascular 25 diseases 26 , 27 and 27 and 28 risk the level of cognition in five different cognitive abilities was also related to incident mobility impairment . 0 ###LEFT-WALL### 2 level 0 ###LEFT-WALL### 12 related 0 ###LEFT-WALL### 17 . 1 the 2 level 2 level 3 of 2 level 10 was 3 of 4 cognition 4 cognition 5 in 5 in 9 abilities 6 five 9 abilities 7 different 9 abilities 8 cognitive 9 abilities 10 was 11 also 10 was 12 related 12 related 13 to 13 to 16 impairment 14 incident 16 impairment 15 mobility 16 impairment cognition showed similar associations with incident loss of the ability to ambulate . 0 ###LEFT-WALL### 1 cognition 0 ###LEFT-WALL### 2 showed 0 ###LEFT-WALL### 13 . 1 cognition 2 showed 2 showed 4 associations 2 showed 5 with 3 similar 4 associations 5 with 7 loss 6 incident 7 loss 7 loss 8 of 8 of 10 ability 9 the 10 ability 10 ability 11 to 10 ability 12 ambulate 11 to 12 ambulate linear mixed - effects models showed that global cognition at baseline was associated with the rate of declining mobility . 0 ###LEFT-WALL### 1 linear 0 ###LEFT-WALL### 2 mixed 0 ###LEFT-WALL### 3 - 0 ###LEFT-WALL### 6 showed 0 ###LEFT-WALL### 20 . 1 linear 2 mixed 3 - 4 effects 4 effects 5 models 4 effects 6 showed 5 models 6 showed 6 showed 7 that 7 that 9 cognition 7 that 13 associated 8 global 9 cognition 9 cognition 10 at 9 cognition 12 was 10 at 11 baseline 12 was 13 associated 13 associated 14 with 14 with 16 rate 15 the 16 rate 16 rate 17 of 17 of 18 declining 18 declining 19 mobility conclusions : among ambulatory elders , cognition is associated with incident mobility impairment and mobility decline . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 6 , 0 ###LEFT-WALL### 17 . 1 conclusions 2 : 2 : 3 among 3 among 5 elders 4 ambulatory 5 elders 6 , 7 cognition 6 , 9 associated 7 cognition 8 is 8 is 9 associated 9 associated 10 with 10 with 14 and 11 incident 13 impairment 12 mobility 13 impairment 13 impairment 14 and 14 and 16 decline 15 mobility 16 decline objective : to determine whether early adult cognitive ability is a risk factor for depressive symptoms in midlife and how genetic and environmental influences explain the association and to examine cross - sectional relationships between depressive symptoms and specific cognitive abilities at midlife . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 4 determine 0 ###LEFT-WALL### 32 - 0 ###LEFT-WALL### 44 . 1 objective 2 : 2 : 3 to 2 : 4 determine 3 to 4 determine 4 determine 5 whether 4 determine 14 for 4 determine 17 in 5 whether 9 ability 5 whether 10 is 6 early 7 adult 7 adult 9 ability 8 cognitive 9 ability 9 ability 10 is 10 is 13 factor 11 a 13 factor 12 risk 13 factor 14 for 16 symptoms 15 depressive 16 symptoms 17 in 19 and 18 midlife 19 and 19 and 20 how 19 and 24 influences 19 and 31 cross 21 genetic 22 and 22 and 23 environmental 22 and 24 influences 24 influences 28 and 25 explain 27 association 25 explain 28 and 26 the 27 association 28 and 29 to 28 and 30 examine 29 to 30 examine 30 examine 31 cross 32 - 38 and 33 sectional 34 relationships 34 relationships 35 between 34 relationships 38 and 35 between 37 symptoms 36 depressive 37 symptoms 38 and 41 abilities 38 and 42 at 39 specific 41 abilities 40 cognitive 41 abilities 42 at 43 midlife design : a 35 [-] year longitudinal and cross - sectional twin study of cognitive aging . 0 ###LEFT-WALL### 1 design 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 17 . 2 : 13 study 3 a 13 study 4 35 6 year 6 year 13 study 7 longitudinal 8 and 8 and 9 cross 8 and 10 - 8 and 13 study 11 sectional 12 twin 12 twin 13 study 13 study 14 of 14 of 16 aging 15 cognitive 16 aging setting : large multicenter study in the united states . 0 ###LEFT-WALL### 1 setting 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 10 . 1 setting 2 : 2 : 5 study 3 large 5 study 4 multicenter 5 study 5 study 6 in 6 in 9 states 7 the 9 states 8 united 9 states participants : one thousand [two] hundred thirty - seven male twins aged 51 to 60 years . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 8 - 0 ###LEFT-WALL### 17 . 1 participants 2 : 2 : 7 thirty 3 one 4 thousand 4 thousand 6 hundred 6 hundred 7 thirty 8 - 11 twins 8 - 12 aged 9 seven 11 twins 10 male 11 twins 11 twins 12 aged 12 aged 16 years 13 51 14 to 14 to 15 60 14 to 16 years measurements : at the age of 20 years and midlife , participants completed the same version of a general cognitive ability test ( armed forces qualification test [ afqt ] ) . 0 ###LEFT-WALL### 1 measurements 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 11 , 0 ###LEFT-WALL### 32 . 1 measurements 2 : 2 : 3 at 3 at 5 age 4 the 5 age 5 age 6 of 6 of 9 and 7 20 8 years 8 years 9 and 9 and 10 midlife 11 , 12 participants 11 , 13 completed 12 participants 13 completed 13 completed 16 version 14 the 15 same 14 the 16 version 16 version 17 of 17 of 22 test 18 a 22 test 19 general 21 ability 20 cognitive 21 ability 21 ability 22 test 22 test 29 afqt 23 ( 29 afqt 24 armed 29 afqt 25 forces 26 qualification 26 qualification 27 test 27 test 29 afqt 28 [ 29 afqt 29 afqt 30 ] 29 afqt 31 ) midlife testing included an extensive neurocognitive protocol assessing processing speed , verbal memory , visual - spatial memory , working memory , executive function , and visual - spatial ability . 0 ###LEFT-WALL### 2 testing 0 ###LEFT-WALL### 3 included 0 ###LEFT-WALL### 31 . 1 midlife 2 testing 2 testing 3 included 3 included 26 and 4 an 5 extensive 4 an 7 protocol 5 extensive 7 protocol 6 neurocognitive 7 protocol 7 protocol 8 assessing 7 protocol 20 working 7 protocol 22 , 8 assessing 10 speed 9 processing 10 speed 10 speed 13 memory 10 speed 18 memory 11 , 13 memory 12 verbal 13 memory 13 memory 14 , 14 , 18 memory 15 visual 16 - 15 visual 18 memory 17 spatial 18 memory 18 memory 19 , 20 working 21 memory 22 , 24 function 22 , 26 and 23 executive 24 function 25 , 26 and 26 and 30 ability 27 visual 28 - 27 visual 30 ability 29 spatial 30 ability participants completed the center for epidemiologic studies depression scale before cognitive testing and provided health and life style information during a medical history interview . 0 ###LEFT-WALL### 16 and 0 ###LEFT-WALL### 25 . 1 participants 13 and 1 participants 16 and 2 completed 4 center 2 completed 10 before 2 completed 13 and 3 the 4 center 4 center 5 for 5 for 9 scale 6 epidemiologic 7 studies 7 studies 8 depression 8 depression 9 scale 10 before 12 testing 11 cognitive 12 testing 13 and 14 provided 13 and 15 health 16 and 19 information 16 and 20 during 17 life 18 style 18 style 19 information 20 during 24 interview 21 a 22 medical 21 a 24 interview 22 medical 23 history 23 history 24 interview results : lower age 20 afqt scores predicted higher levels of depressive symptoms at age 55 years ( r = - [0.16,p] < 0.001 ) . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 26 . 2 : 4 age 2 : 8 predicted 3 lower 4 age 4 age 5 20 4 age 6 afqt 4 age 7 scores 4 age 8 predicted 6 afqt 7 scores 8 predicted 10 levels 8 predicted 14 at 8 predicted 21 - 9 higher 10 levels 10 levels 11 of 11 of 13 symptoms 12 depressive 13 symptoms 14 at 17 years 15 age 17 years 16 55 17 years 18 ( 21 - 19 r 20 = 20 = 21 - 21 - 23 < 21 - 25 ) 23 < 24 0.001 in bivariate twin modeling , 77 % of the correlation between early cognitive ability and midlife depressive symptoms was due to shared genetic influences . 0 ###LEFT-WALL### 7 % 0 ###LEFT-WALL### 19 was 0 ###LEFT-WALL### 25 . 1 in 4 modeling 1 in 5 , 1 in 7 % 2 bivariate 4 modeling 3 twin 4 modeling 6 77 7 % 7 % 8 of 7 % 19 was 8 of 15 and 9 the 10 correlation 10 correlation 11 between 10 correlation 15 and 11 between 14 ability 12 early 14 ability 13 cognitive 14 ability 15 and 18 symptoms 16 midlife 18 symptoms 17 depressive 18 symptoms 19 was 21 to 20 due 21 to 21 to 24 influences 22 shared 24 influences 23 genetic 24 influences controlling for current age , age 20 afqt , and nonindependence ofobservations , depressive symptoms were associated with worse midlife afqt scores and poorer performance in all cognitive domains except verbal memory . 0 ###LEFT-WALL### 15 symptoms 0 ###LEFT-WALL### 17 associated 0 ###LEFT-WALL### 33 . 1 controlling 2 for 1 controlling 12 ofobservations 1 controlling 13 , 1 controlling 15 symptoms 2 for 10 and 3 current 4 age 4 age 5 , 5 , 8 afqt 5 , 10 and 6 age 8 afqt 7 20 8 afqt 9 , 10 and 10 and 11 nonindependence 14 depressive 15 symptoms 15 symptoms 16 were 16 were 17 associated 17 associated 18 with 18 with 23 and 18 with 30 except 19 worse 20 midlife 20 midlife 22 scores 21 afqt 22 scores 22 scores 23 and 23 and 25 performance 23 and 26 in 24 poorer 25 performance 26 in 29 domains 27 all 29 domains 28 cognitive 29 domains 30 except 32 memory 31 verbal 32 memory conclusion : results suggest that low cognitive ability is a risk factor for depressive symptoms ; this association is partly due to shared genetic influences . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 26 . 2 : 3 results 2 : 4 suggest 2 : 16 ; 3 results 4 suggest 4 suggest 5 that 5 that 8 ability 5 that 9 is 6 low 8 ability 7 cognitive 8 ability 8 ability 9 is 9 is 12 factor 10 a 12 factor 11 risk 12 factor 12 factor 13 for 13 for 15 symptoms 14 depressive 15 symptoms 16 ; 18 association 16 ; 19 is 17 this 18 association 18 association 19 is 19 is 20 partly 19 is 22 to 21 due 22 to 22 to 25 influences 23 shared 25 influences 24 genetic 25 influences crosssectional analyses indicate that the association between depressive symptoms and performance is not linked to specific cognitive domains . 0 ###LEFT-WALL### 2 analyses 0 ###LEFT-WALL### 3 indicate 0 ###LEFT-WALL### 19 . 1 crosssectional 2 analyses 2 analyses 3 indicate 3 indicate 4 that 4 that 6 association 4 that 12 is 5 the 6 association 6 association 7 between 6 association 12 is 7 between 10 and 8 depressive 9 symptoms 9 symptoms 10 and 10 and 11 performance 12 is 13 not 12 is 15 to 13 not 14 linked 15 to 18 domains 16 specific 18 domains 17 cognitive 18 domains objectives : to describe preloss and postloss grief symptoms among family members of nursing home ( nh ) residents [with] advanced dementia , and to identify predictors of greater postloss grief symptoms . 0 ###LEFT-WALL### 1 objectives 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 26 identify 0 ###LEFT-WALL### 33 . 2 : 3 to 2 : 4 describe 3 to 4 describe 4 describe 9 symptoms 5 preloss 6 and 6 and 7 postloss 6 and 9 symptoms 8 grief 9 symptoms 9 symptoms 10 among 10 among 12 members 11 family 12 members 12 members 13 of 12 members 19 residents 12 members 26 identify 13 of 14 nursing 14 nursing 15 home 15 home 17 nh 16 ( 17 nh 17 nh 18 ) 19 residents 24 and 21 advanced 22 dementia 21 advanced 24 and 23 , 24 and 24 and 25 to 24 and 26 identify 25 to 26 identify 26 identify 27 predictors 27 predictors 28 of 28 of 32 symptoms 29 greater 30 postloss 30 postloss 32 symptoms 31 grief 32 symptoms design : prospective cohort study . 0 ###LEFT-WALL### 1 design 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 6 . 1 design 2 : 2 : 5 study 3 prospective 4 cohort 4 cohort 5 study setting : 22 nhs in the greater boston area . 0 ###LEFT-WALL### 1 setting 0 ###LEFT-WALL### 2 : 2 : 9 area 2 : 10 . 3 22 9 area 4 nhs 5 in 4 nhs 9 area 5 in 8 boston 6 the 8 boston 7 greater 8 boston participants : 123 family members of nh residents who died with advanced dementia . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 14 . 1 participants 2 : 2 : 5 members 3 123 5 members 4 family 5 members 5 members 6 of 6 of 8 residents 7 nh 8 residents 8 residents 9 who 8 residents 10 died 9 who 10 died 10 died 11 with 11 with 13 dementia 12 advanced 13 dementia measurements : preloss grief was measured at baseline , and postloss grief was measured 2 and 7 months postloss using the prolonged grief disorder scale . 0 ###LEFT-WALL### 1 measurements 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 26 . 2 : 4 grief 2 : 5 was 3 preloss 4 grief 4 grief 5 was 5 was 6 measured 6 measured 7 at 7 at 10 and 8 baseline 10 and 9 , 10 and 10 and 19 postloss 10 and 20 using 11 postloss 12 grief 11 postloss 13 was 11 postloss 14 measured 12 grief 13 was 14 measured 16 and 15 2 16 and 16 and 17 7 17 7 18 months 18 months 19 postloss 20 using 25 scale 21 the 25 scale 22 prolonged 23 grief 23 grief 24 disorder 24 disorder 25 scale independent variables included resident and family member sociodemographic characteristics , resident comfort , acute illness , acute care prior to death , family member depression , and family member understanding of dementia and [of] resident ['s] prognosis . 0 ###LEFT-WALL### 27 and 0 ###LEFT-WALL### 38 . 1 independent 2 variables 2 variables 3 included 2 variables 5 and 3 included 4 resident 5 and 9 characteristics 5 and 12 comfort 5 and 15 illness 5 and 18 care 5 and 27 and 6 family 7 member 7 member 9 characteristics 8 sociodemographic 9 characteristics 10 , 12 comfort 11 resident 12 comfort 12 comfort 13 , 13 , 15 illness 14 acute 15 illness 15 illness 16 , 16 , 18 care 17 acute 18 care 18 care 19 prior 18 care 26 , 19 prior 20 to 20 to 21 death 21 death 25 depression 22 , 25 depression 23 family 25 depression 24 member 25 depression 25 depression 26 , 27 and 30 understanding 27 and 31 of 28 family 29 member 29 member 30 understanding 31 of 33 and 32 dementia 33 and 33 and 37 prognosis 35 resident 37 prognosis results : levels of preloss and postloss grief were relatively stable from baseline to 7 months postloss . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 3 levels 2 : 9 were 2 : 18 . 3 levels 4 of 3 levels 9 were 4 of 6 and 5 preloss 6 and 6 and 8 grief 7 postloss 8 grief 9 were 11 stable 10 relatively 11 stable 11 stable 12 from 11 stable 14 to 12 from 13 baseline 14 to 17 postloss 15 7 16 months 16 months 17 postloss feelings of separation and yearning were the most prominent grief symptoms . 0 ###LEFT-WALL### 1 feelings 0 ###LEFT-WALL### 6 were 0 ###LEFT-WALL### 12 . 1 feelings 2 of 1 feelings 6 were 2 of 4 and 3 separation 4 and 4 and 5 yearning 6 were 11 symptoms 7 the 8 most 8 most 11 symptoms 9 prominent 10 grief 10 grief 11 symptoms after multivariable adjustment , greater preloss grief and the family member having lived with the resident prior to nh admission were the only factors independently associated with greater postloss grief 7 months after resident death . 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 21 were 0 ###LEFT-WALL### 36 . 1 after 3 adjustment 1 after 4 , 1 after 8 and 2 multivariable 3 adjustment 5 greater 6 preloss 6 preloss 7 grief 7 grief 8 and 8 and 11 member 8 and 12 having 8 and 14 with 8 and 21 were 9 the 11 member 10 family 11 member 12 having 13 lived 14 with 16 resident 15 the 16 resident 16 resident 17 prior 17 prior 18 to 18 to 20 admission 19 nh 20 admission 21 were 24 factors 21 were 27 with 21 were 33 after 22 the 23 only 22 the 24 factors 24 factors 26 associated 25 independently 26 associated 27 with 30 grief 28 greater 29 postloss 29 postloss 30 grief 30 grief 31 7 32 months 33 after 33 after 35 death 34 resident 35 death conclusions : the pattern of grieving for some family members of nh residents with advanced dementia is prolonged and begins before resident death . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 24 . 2 : 4 pattern 2 : 19 and 3 the 4 pattern 4 pattern 5 of 4 pattern 19 and 5 of 6 grieving 6 grieving 7 for 7 for 10 members 8 some 10 members 9 family 10 members 10 members 11 of 11 of 13 residents 12 nh 13 residents 13 residents 14 with 14 with 16 dementia 15 advanced 16 dementia 17 is 18 prolonged 17 is 19 and 19 and 20 begins 19 and 21 before 21 before 23 death 22 resident 23 death identification of family members at risk for postloss grief during the preloss period may help guide interventions aimed at lessening postloss grief . 0 ###LEFT-WALL### 1 identification 0 ###LEFT-WALL### 16 guide 0 ###LEFT-WALL### 23 . 1 identification 2 of 1 identification 5 at 1 identification 14 may 2 of 4 members 3 family 4 members 5 at 6 risk 6 risk 7 for 6 risk 10 during 7 for 9 grief 8 postloss 9 grief 10 during 13 period 11 the 13 period 12 preloss 13 period 14 may 15 help 15 help 16 guide 16 guide 17 interventions 16 guide 19 at 17 interventions 18 aimed 19 at 20 lessening 20 lessening 22 grief 21 postloss 22 grief objectives : the primary objective of this study was to determine whether caregiving burden mediated the relationship between specific behavior disturbances and time to nursing home admission ( nha ) for persons with dementia ( i.e [.] , alzheimer disease or a related disorder ) . 0 ###LEFT-WALL### 1 objectives 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 11 determine 1 objectives 2 : 2 : 5 objective 3 the 5 objective 4 primary 5 objective 5 objective 6 of 6 of 7 this 8 study 9 was 9 was 10 to 9 was 11 determine 10 to 11 determine 11 determine 12 whether 11 determine 18 between 11 determine 24 to 11 determine 46 . 12 whether 14 burden 12 whether 15 mediated 13 caregiving 14 burden 14 burden 15 mediated 15 mediated 17 relationship 16 the 17 relationship 18 between 22 and 19 specific 21 disturbances 20 behavior 21 disturbances 21 disturbances 22 and 22 and 23 time 24 to 25 nursing 25 nursing 26 home 25 nursing 27 admission 25 nursing 31 for 25 nursing 33 with 27 admission 29 nha 28 ( 29 nha 29 nha 30 ) 31 for 32 persons 33 with 34 dementia 34 dementia 36 i.e 35 ( 36 i.e 36 i.e 41 or 36 i.e 45 ) 38 , 41 or 39 alzheimer 40 disease 40 disease 41 or 41 or 44 disorder 41 or 45 ) 42 a 44 disorder 43 related 44 disorder design : the study used secondary longitudinal data from the medicare alzheimer 's disease demonstration , a medicare - covered home care benefit and case management program for family caregivers of persons with dementia . 0 ###LEFT-WALL### 1 design 0 ###LEFT-WALL### 2 : 2 : 24 and 2 : 35 . 3 the 8 data 4 study 5 used 5 used 8 data 6 secondary 8 data 7 longitudinal 8 data 8 data 9 from 8 data 24 and 9 from 23 benefit 10 the 12 alzheimer 11 medicare 12 alzheimer 12 alzheimer 13 's 13 's 23 benefit 14 disease 15 demonstration 15 demonstration 18 medicare 15 demonstration 23 benefit 16 , 18 medicare 17 a 18 medicare 18 medicare 19 - 20 covered 21 home 21 home 23 benefit 22 care 23 benefit 24 and 27 program 24 and 28 for 25 case 26 management 26 management 27 program 28 for 30 caregivers 29 family 30 caregivers 30 caregivers 31 of 30 caregivers 33 with 31 of 32 persons 33 with 34 dementia primary caregivers of persons with dementia were assessed [via] in [-] person and telephone interviews every 6 months over a 3 [-] year period . 0 ###LEFT-WALL### 2 caregivers 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 25 . 1 primary 2 caregivers 2 caregivers 3 of 2 caregivers 13 and 3 of 4 persons 4 persons 5 with 5 with 6 dementia 7 were 8 assessed 7 were 13 and 8 assessed 12 person 10 in 12 person 13 and 14 telephone 13 and 19 over 14 telephone 15 interviews 15 interviews 16 every 16 every 18 months 17 6 18 months 19 over 24 period 20 a 24 period 21 3 23 year 23 year 24 period setting : dementia caregivers were recruited from eight catchment areas throughout the united states . 0 ###LEFT-WALL### 1 setting 0 ###LEFT-WALL### 2 : 2 : 4 caregivers 2 : 6 recruited 2 : 15 . 3 dementia 4 caregivers 4 caregivers 5 were 5 were 6 recruited 6 recruited 7 from 6 recruited 11 throughout 7 from 10 areas 8 eight 10 areas 9 catchment 10 areas 11 throughout 14 states 12 the 14 states 13 united 14 states participants : the baseline sample included 5,831 dementia caregivers . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 2 : 2 : 5 sample 2 : 6 included 2 : 10 . 3 the 5 sample 4 baseline 5 sample 5 sample 6 included 6 included 9 caregivers 7 5,831 9 caregivers 8 dementia 9 caregivers just more than 40 % ( 43.9 % [;] n = 2,556 ) [of] persons with dementia permanently entered a nursing home during the 3 - year study period . 0 ###LEFT-WALL### 15 persons 0 ###LEFT-WALL### 19 entered 0 ###LEFT-WALL### 26 - 1 just 2 more 1 just 3 than 1 just 11 = 1 just 13 ) 1 just 15 persons 3 than 5 % 4 40 5 % 6 ( 11 = 7 43.9 10 n 8 % 10 n 10 n 11 = 11 = 12 2,556 11 = 13 ) 15 persons 16 with 15 persons 19 entered 16 with 17 dementia 18 permanently 19 entered 19 entered 22 home 19 entered 23 during 20 a 21 nursing 20 a 22 home 21 nursing 22 home 23 during 25 3 24 the 25 3 26 - 29 period 26 - 30 . 27 year 29 period 28 study 29 period measurements : individual behavior problems were measured with the memory and behavior problem checklist . 0 ###LEFT-WALL### 1 measurements 0 ###LEFT-WALL### 2 : 2 : 5 problems 2 : 7 measured 2 : 15 . 3 individual 5 problems 4 behavior 5 problems 5 problems 6 were 6 were 7 measured 7 measured 8 with 8 with 14 checklist 9 the 14 checklist 10 memory 11 and 11 and 12 behavior 12 behavior 13 problem 13 problem 14 checklist caregiving burden was assessed with a short version of the zarit burden inventory . 0 ###LEFT-WALL### 2 burden 0 ###LEFT-WALL### 4 assessed 0 ###LEFT-WALL### 14 . 1 caregiving 2 burden 2 burden 3 was 3 was 4 assessed 4 assessed 5 with 5 with 8 version 6 a 7 short 6 a 8 version 7 short 8 version 8 version 9 of 9 of 13 inventory 10 the 13 inventory 11 zarit 12 burden 12 burden 13 inventory key covariates , including sociodemographic background , functional status , and service utilization , were also considered . 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 17 considered 0 ###LEFT-WALL### 18 . 1 key 2 covariates 2 covariates 3 , 3 , 6 background 3 , 7 , 4 including 6 background 5 sociodemographic 6 background 7 , 9 status 7 , 11 and 8 functional 9 status 10 , 11 and 11 and 13 utilization 11 and 14 , 11 and 15 were 12 service 13 utilization 15 were 17 considered 16 also 17 considered results : event history analyses revealed that time - varying measures of caregiver burden fully mediated the relationship between four behavioral disturbances ( episodes of combativeness , property destruction , repetitive questions , and [reliving] the past ) and nha . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 41 . 1 results 2 : 2 : 39 and 3 event 16 mediated 3 event 34 and 4 history 5 analyses 5 analyses 6 revealed 6 revealed 11 measures 6 revealed 16 mediated 7 that 8 time 8 time 9 - 8 time 11 measures 10 varying 11 measures 11 measures 12 of 11 measures 16 mediated 12 of 14 burden 13 caregiver 14 burden 15 fully 16 mediated 16 mediated 18 relationship 16 mediated 33 , 17 the 18 relationship 18 relationship 19 between 19 between 22 disturbances 20 four 22 disturbances 21 behavioral 22 disturbances 22 disturbances 24 episodes 22 disturbances 29 destruction 23 ( 24 episodes 24 episodes 25 of 24 episodes 27 , 25 of 26 combativeness 27 , 29 destruction 28 property 29 destruction 29 destruction 32 questions 29 destruction 33 , 30 , 32 questions 31 repetitive 32 questions 32 questions 33 , 33 , 34 and 34 and 37 past 34 and 38 ) 34 and 39 and 36 the 37 past 39 and 40 nha conclusions : the findings highlight the multifaceted , complex pathway to nha for persons with dementia and their family caregivers . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 21 . 2 : 4 findings 2 : 5 highlight 3 the 4 findings 4 findings 5 highlight 5 highlight 10 pathway 5 highlight 11 to 5 highlight 13 for 5 highlight 15 with 6 the 10 pathway 7 multifaceted 8 , 7 multifaceted 9 complex 9 complex 10 pathway 11 to 12 nha 13 for 14 persons 15 with 17 and 16 dementia 17 and 17 and 20 caregivers 18 their 20 caregivers 19 family 20 caregivers the results emphasize the need for comprehensive treatment approaches that incorporate the burden of caregivers and the behavioral/psychiatric symptoms of persons with dementia simultaneously . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 emphasize 0 ###LEFT-WALL### 25 . 1 the 2 results 2 results 3 emphasize 3 emphasize 5 need 4 the 5 need 5 need 6 for 6 for 9 approaches 7 comprehensive 8 treatment 8 treatment 9 approaches 9 approaches 10 that 9 approaches 11 incorporate 10 that 11 incorporate 11 incorporate 13 burden 11 incorporate 22 with 11 incorporate 24 simultaneously 12 the 13 burden 13 burden 14 of 13 burden 20 of 14 of 16 and 15 caregivers 16 and 16 and 19 symptoms 17 the 19 symptoms 18 behavioral/psychiatric 19 symptoms 20 of 21 persons 22 with 23 dementia in this review , we discuss recent research in the field of human skeletal muscle protein metabolism characterizing the acute regulation of mammalian target [of] rapamycin complex ( mtorc ) 1 signaling and muscle protein synthesis ( mps ) by exercise , amino acid nutrition , and aging . 0 ###LEFT-WALL### 5 we 0 ###LEFT-WALL### 6 discuss 0 ###LEFT-WALL### 42 , 0 ###LEFT-WALL### 49 . 1 in 3 review 1 in 4 , 1 in 5 we 2 this 3 review 5 we 6 discuss 6 discuss 8 research 7 recent 8 research 8 research 9 in 8 research 18 characterizing 9 in 11 field 10 the 11 field 11 field 12 of 12 of 17 metabolism 13 human 15 muscle 14 skeletal 15 muscle 15 muscle 17 metabolism 16 protein 17 metabolism 18 characterizing 21 regulation 18 characterizing 40 by 19 the 21 regulation 20 acute 21 regulation 21 regulation 22 of 22 of 36 synthesis 23 mammalian 24 target 24 target 26 rapamycin 26 rapamycin 35 protein 27 complex 29 mtorc 27 complex 35 protein 28 ( 29 mtorc 29 mtorc 30 ) 31 1 32 signaling 32 signaling 33 and 33 and 34 muscle 33 and 35 protein 35 protein 36 synthesis 36 synthesis 38 mps 37 ( 38 mps 38 mps 39 ) 40 by 41 exercise 42 , 47 and 43 amino 45 nutrition 44 acid 45 nutrition 45 nutrition 47 and 46 , 47 and 47 and 48 aging resistance exercise performed in the [fasted] state stimulates mixed mps within 1 h after exercise , which can remain elevated for 48 h . 0 ###LEFT-WALL### 1 resistance 0 ###LEFT-WALL### 9 mixed 0 ###LEFT-WALL### 16 , 0 ###LEFT-WALL### 20 elevated 0 ###LEFT-WALL### 24 . 1 resistance 2 exercise 1 resistance 8 stimulates 1 resistance 9 mixed 2 exercise 3 performed 2 exercise 8 stimulates 3 performed 4 in 4 in 7 state 5 the 7 state 9 mixed 10 mps 9 mixed 11 within 9 mixed 14 after 11 within 13 h 12 1 13 h 14 after 15 exercise 16 , 17 which 16 , 19 remain 17 which 18 can 18 can 19 remain 19 remain 20 elevated 20 elevated 21 for 21 for 23 h 22 48 23 h we demonstrate that the activation of mtorc1 signaling ( and subsequently enhanced translation initiation ) is required for the contraction [-] induced increase in mps . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 demonstrate 0 ###LEFT-WALL### 26 . 1 we 2 demonstrate 2 demonstrate 3 that 3 that 5 activation 3 that 17 required 4 the 5 activation 5 activation 6 of 5 activation 16 is 6 of 10 and 7 mtorc1 8 signaling 7 mtorc1 10 and 9 ( 10 and 10 and 14 initiation 10 and 15 ) 11 subsequently 12 enhanced 12 enhanced 13 translation 13 translation 14 initiation 16 is 17 required 17 required 18 for 17 required 24 in 18 for 23 increase 19 the 23 increase 20 contraction 22 induced 22 induced 23 increase 24 in 25 mps in comparison , low - intensity blood flow [restriction] ( bfr ) exercise stimulates mps and mtorc1 signaling to an extent similar to traditional , high - intensity resistance exercise . 0 ###LEFT-WALL### 13 exercise 0 ###LEFT-WALL### 14 stimulates 0 ###LEFT-WALL### 31 . 1 in 2 comparison 1 in 13 exercise 2 comparison 8 flow 3 , 8 flow 4 low 5 - 4 low 6 intensity 6 intensity 8 flow 7 blood 8 flow 8 flow 11 bfr 8 flow 12 ) 10 ( 11 bfr 11 bfr 12 ) 13 exercise 14 stimulates 14 stimulates 16 and 15 mps 16 and 16 and 17 mtorc1 17 mtorc1 18 signaling 17 mtorc1 19 to 17 mtorc1 22 similar 19 to 21 extent 20 an 21 extent 22 similar 23 to 23 to 30 exercise 24 traditional 25 , 24 traditional 30 exercise 26 high 27 - 26 high 30 exercise 28 intensity 29 resistance 29 resistance 30 exercise we also show that mtorc1 signaling is required for the essential amino acid ( eaa ) - induced increase in mps . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 show 0 ###LEFT-WALL### 22 . 1 we 3 show 2 also 3 show 3 show 4 that 4 that 5 mtorc1 4 that 8 required 5 mtorc1 6 signaling 5 mtorc1 7 is 7 is 8 required 8 required 9 for 8 required 20 in 9 for 19 increase 10 the 19 increase 11 essential 19 increase 12 amino 19 increase 13 acid 15 eaa 13 acid 17 - 13 acid 19 increase 14 ( 15 eaa 15 eaa 16 ) 18 induced 19 increase 20 in 21 mps ingestion of eaas ( or protein ) shortly after resistance exercise enhances mps and mtorc1 signaling compared with resistance exercise or eaas alone . 0 ###LEFT-WALL### 5 or 0 ###LEFT-WALL### 12 enhances 0 ###LEFT-WALL### 14 and 0 ###LEFT-WALL### 24 . 1 ingestion 2 of 1 ingestion 5 or 2 of 3 eaas 4 ( 5 or 5 or 6 protein 5 or 7 ) 5 or 9 after 5 or 12 enhances 8 shortly 9 after 9 after 11 exercise 10 resistance 11 exercise 12 enhances 13 mps 14 and 15 mtorc1 14 and 17 compared 15 mtorc1 16 signaling 15 mtorc1 17 compared 17 compared 18 with 17 compared 23 alone 18 with 21 or 19 resistance 20 exercise 20 exercise 21 or 21 or 22 eaas in older adults , the ability of the skeletal muscle to respond to anabolic stimuli is impaired . 0 ###LEFT-WALL### 6 ability 0 ###LEFT-WALL### 17 impaired 0 ###LEFT-WALL### 18 . 1 in 3 adults 1 in 4 , 1 in 6 ability 2 older 3 adults 5 the 6 ability 6 ability 7 of 6 ability 11 to 6 ability 12 respond 6 ability 16 is 7 of 10 muscle 8 the 10 muscle 9 skeletal 10 muscle 11 to 12 respond 12 respond 13 to 13 to 15 stimuli 14 anabolic 15 stimuli 16 is 17 impaired for example , in response to an acute bout of resistance exercise , older adults are less able to activate mtorc1 or increase mps during the first 24 h of postexercise recovery . 0 ###LEFT-WALL### 15 adults 0 ###LEFT-WALL### 16 are 0 ###LEFT-WALL### 33 . 1 for 2 example 2 example 3 , 2 example 15 adults 3 , 6 to 4 in 5 response 5 response 6 to 6 to 9 bout 6 to 13 , 6 to 15 adults 7 an 9 bout 8 acute 9 bout 9 bout 10 of 10 of 12 exercise 11 resistance 12 exercise 14 older 15 adults 15 adults 16 are 16 are 18 able 17 less 18 able 18 able 19 to 18 able 22 or 19 to 22 or 20 activate 21 mtorc1 20 activate 22 or 22 or 23 increase 22 or 29 h 23 increase 24 mps 24 mps 25 during 25 during 27 first 26 the 27 first 28 24 29 h 29 h 30 of 30 of 32 recovery 31 postexercise 32 recovery however , bfr exercise can overcome this impairment . 0 ###LEFT-WALL### 4 exercise 0 ###LEFT-WALL### 6 overcome 0 ###LEFT-WALL### 9 . 1 however 2 , 1 however 4 exercise 3 bfr 4 exercise 4 exercise 5 can 5 can 6 overcome 6 overcome 8 impairment 7 this 8 impairment aging is not associated with a reduced response to eaas provided the eaa content is sufficient . 0 ###LEFT-WALL### 1 aging 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 17 . 1 aging 2 is 2 is 3 not 2 is 5 with 2 is 9 to 2 is 11 provided 3 not 4 associated 5 with 8 response 6 a 8 response 7 reduced 8 response 9 to 10 eaas 11 provided 14 content 11 provided 15 is 12 the 14 content 13 eaa 14 content 14 content 15 is 15 is 16 sufficient therefore , we propose that exercise combined with eaa should be effective not only in improving muscle repair and growth in response to training in athletes , but that strategies such as eaa combined with resistance exercise ( or bfr exercise ) may be very useful as a countermeasure for sarcopenia and other clinical conditions associated with muscle wasting . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 propose 0 ###LEFT-WALL### 13 not 0 ###LEFT-WALL### 60 . 1 therefore 2 , 1 therefore 3 we 3 we 4 propose 4 propose 5 that 5 that 6 exercise 5 that 11 be 6 exercise 7 combined 6 exercise 8 with 6 exercise 10 should 8 with 9 eaa 10 should 11 be 11 be 12 effective 13 not 14 only 13 not 30 strategies 13 not 34 combined 15 in 19 and 15 in 27 , 15 in 30 strategies 16 improving 17 muscle 17 muscle 18 repair 18 repair 19 and 19 and 20 growth 20 growth 22 response 20 growth 23 to 21 in 22 response 23 to 24 training 24 training 25 in 25 in 26 athletes 28 but 29 that 28 but 30 strategies 30 strategies 32 as 30 strategies 34 combined 31 such 32 as 32 as 33 eaa 34 combined 35 with 35 with 36 resistance 36 resistance 39 or 36 resistance 44 be 36 resistance 46 useful 37 exercise 39 or 38 ( 39 or 39 or 41 exercise 39 or 42 ) 39 or 43 may 40 bfr 41 exercise 43 may 44 be 45 very 46 useful 46 useful 47 as 47 as 52 and 48 a 49 countermeasure 49 countermeasure 50 for 49 countermeasure 52 and 50 for 51 sarcopenia 52 and 53 other 52 and 55 conditions 52 and 59 wasting 54 clinical 55 conditions 55 conditions 56 associated 56 associated 57 with 57 with 58 muscle 57 with 59 wasting background and aims : increased fear of falling is associated with greater muscular coactivation during standing postural control . 0 ###LEFT-WALL### 3 aims 0 ###LEFT-WALL### 4 : 0 ###LEFT-WALL### 19 . 1 background 2 and 2 and 3 aims 4 : 6 fear 4 : 10 associated 5 increased 6 fear 6 fear 7 of 6 fear 9 is 7 of 8 falling 9 is 10 associated 10 associated 11 with 10 associated 15 during 11 with 14 coactivation 12 greater 14 coactivation 13 muscular 14 coactivation 15 during 18 control 16 standing 18 control 17 postural 18 control excessive muscular coactivation reduces the performance of agonist muscles . 0 ###LEFT-WALL### 3 coactivation 0 ###LEFT-WALL### 4 reduces 0 ###LEFT-WALL### 10 . 1 excessive 3 coactivation 2 muscular 3 coactivation 3 coactivation 4 reduces 4 reduces 6 performance 5 the 6 performance 6 performance 7 of 7 of 9 muscles 8 agonist 9 muscles although several recent studies have observed increased muscular coactivation during walking in older adults , little is known about the relationship between fear of falling and muscular coactivation [during] walking . 0 ###LEFT-WALL### 16 little 0 ###LEFT-WALL### 18 known 0 ###LEFT-WALL### 31 . 1 although 2 several 1 although 16 little 2 several 4 studies 2 several 10 during 2 several 11 walking 3 recent 4 studies 4 studies 5 have 5 have 6 observed 6 observed 9 coactivation 6 observed 10 during 7 increased 9 coactivation 8 muscular 9 coactivation 12 in 14 adults 12 in 15 , 12 in 16 little 13 older 14 adults 16 little 17 is 17 is 18 known 18 known 19 about 18 known 22 between 19 about 21 relationship 20 the 21 relationship 22 between 26 and 23 fear 24 of 23 fear 26 and 24 of 25 falling 26 and 28 coactivation 26 and 30 walking 27 muscular 28 coactivation the purpose of this study was to compare muscular coactivation [during] walking between older adults with fear of falling and older adults without fear of falling . 0 ###LEFT-WALL### 2 purpose 0 ###LEFT-WALL### 27 . 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 compare 7 to 8 compare 8 compare 10 coactivation 8 compare 13 between 8 compare 16 with 9 muscular 10 coactivation 10 coactivation 12 walking 13 between 15 adults 14 older 15 adults 16 with 22 adults 17 fear 18 of 17 fear 20 and 18 of 19 falling 20 and 21 older 20 and 22 adults 22 adults 23 without 22 adults 25 of 23 without 24 fear 25 of 26 falling methods : thirty - eight healthy older adults ( 82.3 ± 6.8 years ) participated in this study . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 8 adults 2 : 15 participated 2 : 19 . 3 thirty 4 - 4 - 5 eight 4 - 8 adults 6 healthy 8 adults 7 older 8 adults 8 adults 13 years 8 adults 15 participated 9 ( 13 years 10 82.3 13 years 11 ± 13 years 12 6.8 13 years 13 years 14 ) 15 participated 16 in 16 in 18 study 17 this 18 study [walking] speed and step length were measured . 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 6 were 0 ###LEFT-WALL### 8 . 2 speed 3 and 3 and 5 length 3 and 6 were 4 step 5 length 6 were 7 measured electromyography ( emg ) data were collected from the tibialis anterior and soleus [during] walking to calculate the co - contraction index ( ci ) . 0 ###LEFT-WALL### 5 data 0 ###LEFT-WALL### 26 . 1 electromyography 3 emg 1 electromyography 5 data 2 ( 3 emg 3 emg 4 ) 5 data 6 were 6 were 7 collected 7 collected 8 from 8 from 10 tibialis 9 the 10 tibialis 10 tibialis 12 and 10 tibialis 22 index 10 tibialis 24 ci 11 anterior 12 and 12 and 13 soleus 12 and 15 walking 12 and 22 index 15 walking 16 to 16 to 17 calculate 17 calculate 21 contraction 18 the 21 contraction 19 co 20 - 19 co 21 contraction 23 ( 24 ci 24 ci 25 ) subjects were divided into those with fear of falling and those without fear of falling , on the basis of a modified falls efficacy scale ( fes ) . 0 ###LEFT-WALL### 1 subjects 0 ###LEFT-WALL### 3 divided 0 ###LEFT-WALL### 29 . 1 subjects 2 were 2 were 3 divided 3 divided 4 into 3 divided 12 without 4 into 10 and 5 those 6 with 5 those 10 and 6 with 7 fear 7 fear 8 of 8 of 9 falling 10 and 11 those 12 without 13 fear 13 fear 14 of 13 fear 17 on 14 of 15 falling 16 , 17 on 17 on 19 basis 17 on 28 ) 18 the 19 basis 19 basis 20 of 20 of 27 fes 21 a 27 fes 22 modified 27 fes 23 falls 24 efficacy 24 efficacy 25 scale 25 scale 27 fes 26 ( 27 fes 27 fes 28 ) stepwise multiple regression analysis was used , with ci as the dependent variable , and fear of falling , experience of falling ( during the past year ) , walking speed , step length , and age as independent variables . 0 ###LEFT-WALL### 4 analysis 0 ###LEFT-WALL### 6 used 1 stepwise 4 analysis 2 multiple 4 analysis 3 regression 4 analysis 4 analysis 5 was 5 was 6 used 6 used 8 with 7 , 8 with 8 with 15 and 8 with 41 . 9 ci 10 as 9 ci 15 and 10 as 13 variable 11 the 13 variable 12 dependent 13 variable 14 , 15 and 15 and 16 fear 16 fear 17 of 16 fear 30 walking 17 of 18 falling 18 falling 20 experience 19 , 20 experience 20 experience 21 of 20 experience 29 , 21 of 22 falling 22 falling 24 during 23 ( 24 during 24 during 27 year 24 during 28 ) 25 the 26 past 25 the 27 year 30 walking 36 and 31 speed 32 , 32 , 34 length 32 , 36 and 33 step 34 length 35 , 36 and 36 and 37 age 36 and 38 as 38 as 40 variables 39 independent 40 variables results : mean values of ci during walking , walking speed , and step length were [51.9] ± 11.7 % , 0.90 ± 0.40 m / [s] , and 0.43±0.11 [m] , respectively . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 34 . 1 results 2 : 2 : 3 mean 3 mean 4 values 3 mean 11 speed 4 values 5 of 4 values 11 speed 5 of 6 ci 6 ci 7 during 7 during 9 , 8 walking 9 , 9 , 10 walking 12 , 13 and 13 and 15 length 13 and 18 ± 14 step 15 length 15 length 16 were 16 were 18 ± 18 ± 20 % 18 ± 33 respectively 19 11.7 20 % 20 % 29 and 21 , 29 and 22 0.90 23 ± 23 ± 26 / 24 0.40 25 m 25 m 26 / 26 / 29 and 28 , 29 and 29 and 30 0.43±0.11 29 and 32 , eight subjects ( 21.1 % ) had fallen within the past year , and 19 subjects ( 50.0 % ) had fear of falling . 0 ###LEFT-WALL### 2 subjects 0 ###LEFT-WALL### 8 fallen 0 ###LEFT-WALL### 14 and 0 ###LEFT-WALL### 25 . 1 eight 2 subjects 2 subjects 5 % 2 subjects 7 had 3 ( 5 % 4 21.1 5 % 5 % 6 ) 7 had 8 fallen 8 fallen 9 within 9 within 12 year 10 the 12 year 11 past 12 year 13 , 14 and 14 and 16 subjects 14 and 21 had 15 19 16 subjects 16 subjects 19 % 16 subjects 21 had 17 ( 19 % 18 50.0 19 % 19 % 20 ) 21 had 22 fear 22 fear 23 of 23 of 24 falling all subjects without fear of falling had fes scores of 10 [(] [maximum] score [ )( 0 ###LEFT-WALL### 2 subjects 0 ###LEFT-WALL### 14 score 0 ###LEFT-WALL### 16 )( 1 all 2 subjects 2 subjects 3 without 2 subjects 5 of 2 subjects 7 had 3 without 4 fear 5 of 6 falling 7 had 9 scores 7 had 14 score 8 fes 9 scores 9 scores 10 of 10 of 11 10 subjects with fear of falling had a median fes score of 17 ( interquartile range , 13 to 25 ) . 0 ###LEFT-WALL### 1 subjects 0 ###LEFT-WALL### 6 had 0 ###LEFT-WALL### 21 . 1 subjects 2 with 1 subjects 4 of 1 subjects 6 had 2 with 3 fear 4 of 5 falling 6 had 10 score 7 a 10 score 8 median 10 score 9 fes 10 score 10 score 11 of 10 score 15 range 11 of 12 17 13 ( 15 range 14 interquartile 15 range 15 range 18 to 15 range 20 ) 16 , 18 to 17 13 18 to 18 to 19 25 18 to 20 ) stepwise multiple regression analysis revealed that fear of falling remained significantly associated with ci ( p<0.01 ) : cis for subjects with fear and those without fear were [59.5] ± 12.2 % and 46.7 ± 8.5 % , respectively . 0 ###LEFT-WALL### 4 analysis 0 ###LEFT-WALL### 18 : 1 stepwise 3 regression 2 multiple 3 regression 3 regression 4 analysis 4 analysis 5 revealed 4 analysis 6 that 4 analysis 10 remained 4 analysis 12 associated 6 that 7 fear 6 that 10 remained 7 fear 8 of 7 fear 10 remained 8 of 9 falling 11 significantly 12 associated 12 associated 13 with 13 with 14 ci 14 ci 16 p<0.01 15 ( 16 p<0.01 16 p<0.01 17 ) 18 : 30 ± 18 : 33 and 19 cis 20 for 19 cis 24 and 20 for 21 subjects 21 subjects 22 with 22 with 23 fear 24 and 25 those 24 and 26 without 24 and 28 were 26 without 27 fear 28 were 30 ± 30 ± 32 % 31 12.2 32 % 33 and 34 46.7 33 and 35 ± 34 46.7 35 ± 35 ± 37 % 35 ± 39 respectively 36 8.5 37 % 38 , 39 respectively 39 respectively 40 . conclusion : individuals with a fear of falling have increased muscular co - activation at the ankle joint [during] walking , at least in a certain subgroup of older adults . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 31 . 2 : 3 individuals 2 : 10 increased 3 individuals 4 with 3 individuals 7 of 3 individuals 9 have 4 with 6 fear 5 a 6 fear 7 of 8 falling 9 have 10 increased 10 increased 12 co 10 increased 23 least 10 increased 24 in 11 muscular 12 co 12 co 14 activation 13 - 14 activation 14 activation 15 at 14 activation 21 , 15 at 18 joint 16 the 18 joint 17 ankle 18 joint 18 joint 20 walking 22 at 23 least 24 in 27 subgroup 25 a 26 certain 25 a 27 subgroup 26 certain 27 subgroup 27 subgroup 28 of 28 of 30 adults 29 older 30 adults further research is needed to clarify negative and positive effects of muscular coactivation [during] walking in fearful subjects . 0 ###LEFT-WALL### 2 research 0 ###LEFT-WALL### 6 clarify 0 ###LEFT-WALL### 19 . 1 further 2 research 2 research 3 is 3 is 4 needed 4 needed 5 to 5 to 6 clarify 6 clarify 10 effects 6 clarify 16 in 7 negative 8 and 8 and 9 positive 8 and 10 effects 10 effects 11 of 11 of 13 coactivation 12 muscular 13 coactivation 13 coactivation 15 walking 16 in 18 subjects 17 fearful 18 subjects background : previous research has investigated differences in the predictive power of self [-] rated health ( srh ) for mortality based on socioeconomic status ( ses ) . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 4 research 2 : 6 investigated 2 : 29 . 3 previous 4 research 4 research 5 has 5 has 6 investigated 6 investigated 7 differences 6 investigated 8 in 6 investigated 20 for 8 in 11 power 9 the 11 power 10 predictive 11 power 11 power 12 of 12 of 16 health 13 self 15 rated 15 rated 16 health 16 health 18 srh 17 ( 18 srh 18 srh 19 ) 20 for 21 mortality 21 mortality 22 based 21 mortality 27 ses 22 based 23 on 23 on 25 status 24 socioeconomic 25 status 26 ( 27 ses 27 ses 28 ) however , these studies mainly assessed adults in the general population and did not focus specifically on elderly adults . 0 ###LEFT-WALL### 4 studies 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 20 . 1 however 2 , 1 however 4 studies 3 these 4 studies 4 studies 12 and 5 mainly 6 assessed 6 assessed 7 adults 6 assessed 8 in 6 assessed 12 and 8 in 11 population 9 the 11 population 10 general 11 population 12 and 13 did 13 did 14 not 13 did 15 focus 15 focus 16 specifically 15 focus 17 on 17 on 19 adults 18 elderly 19 adults in addition , this predictive power has never been evaluated using subjective ses , which is an important measure of ses in elderly adults . 0 ###LEFT-WALL### 6 power 0 ###LEFT-WALL### 10 evaluated 0 ###LEFT-WALL### 14 , 0 ###LEFT-WALL### 25 . 1 in 2 addition 1 in 3 , 1 in 6 power 4 this 5 predictive 5 predictive 6 power 6 power 7 has 7 has 9 been 8 never 9 been 9 been 10 evaluated 10 evaluated 11 using 11 using 13 ses 12 subjective 13 ses 14 , 15 which 14 , 16 is 15 which 16 is 16 is 21 ses 17 an 18 important 17 an 19 measure 18 important 19 measure 19 measure 20 of 19 measure 21 ses 20 of 21 ses 21 ses 22 in 22 in 24 adults 23 elderly 24 adults methods : this study used data from the survey of the health and living status of the middle aged and the elderly in taiwan ( shls ) conducted by the bureau of health promotion , taiwan . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 13 and 1 methods 2 : 2 : 6 data 3 this 6 data 4 study 5 used 5 used 6 data 6 data 7 from 7 from 9 survey 8 the 9 survey 9 survey 10 of 10 of 12 health 11 the 12 health 13 and 15 status 13 and 28 conducted 14 living 15 status 15 status 16 of 15 status 23 in 15 status 28 conducted 16 of 20 and 17 the 19 aged 18 middle 19 aged 19 aged 20 and 20 and 22 elderly 21 the 22 elderly 23 in 24 taiwan 24 taiwan 26 shls 25 ( 26 shls 26 shls 27 ) 28 conducted 29 by 29 by 31 bureau 30 the 31 bureau 31 bureau 32 of 32 of 34 promotion 33 health 34 promotion 34 promotion 36 taiwan 35 , 36 taiwan 36 taiwan 37 . the shls is a 15 [-] year longitudinal survey based on a nationally representative sample . 0 ###LEFT-WALL### 2 shls 0 ###LEFT-WALL### 3 is 0 ###LEFT-WALL### 16 . 1 the 2 shls 2 shls 3 is 3 is 9 survey 4 a 9 survey 5 15 7 year 7 year 9 survey 8 longitudinal 9 survey 9 survey 10 based 10 based 11 on 11 on 15 sample 12 a 13 nationally 12 a 15 sample 13 nationally 14 representative 14 representative 15 sample it was initiated in 1989 with 4049 respondents aged 60 years or older . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 3 initiated 0 ###LEFT-WALL### 14 . 1 it 2 was 2 was 3 initiated 3 initiated 4 in 4 in 5 1989 5 1989 6 with 5 1989 9 aged 6 with 8 respondents 7 4049 8 respondents 9 aged 12 or 10 60 11 years 11 years 12 or 12 or 13 older both education and subjective financial satisfaction were used as ses measures in the present study . 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 8 used 0 ###LEFT-WALL### 16 . 1 both 3 and 2 education 3 and 3 and 6 satisfaction 3 and 7 were 4 subjective 6 satisfaction 5 financial 6 satisfaction 7 were 8 used 8 used 9 as 8 used 12 in 9 as 11 measures 10 ses 11 measures 12 in 15 study 13 the 15 study 14 present 15 study a cox regression model was used to estimate the interaction between srh and ses for 3829 individuals without missing data . 0 ###LEFT-WALL### 4 model 0 ###LEFT-WALL### 6 used 0 ###LEFT-WALL### 21 . 1 a 4 model 2 cox 4 model 3 regression 4 model 4 model 5 was 5 was 6 used 6 used 7 to 6 used 11 between 6 used 18 without 7 to 8 estimate 8 estimate 10 interaction 9 the 10 interaction 11 between 14 ses 12 srh 13 and 13 and 14 ses 14 ses 15 for 15 for 17 individuals 16 3829 17 individuals 18 without 19 missing 19 missing 20 data this hr was significantly higher than those for adults with middle [(] 1.16 , 0.93 - 1.44 ) and low ( 1.27 , 1.05 - 1.54 ) education , based on the χ ( 2 ) test ( p < 0.05 for both comparisons ) . 0 ###LEFT-WALL### 2 hr 0 ###LEFT-WALL### 3 was 0 ###LEFT-WALL### 46 . 1 this 2 hr 2 hr 3 was 3 was 4 significantly 3 was 5 higher 5 higher 6 than 5 higher 30 based 6 than 19 and 7 those 8 for 7 those 19 and 8 for 9 adults 9 adults 10 with 9 adults 16 - 10 with 11 middle 11 middle 13 1.16 14 , 16 - 15 0.93 16 - 16 - 17 1.44 16 - 18 ) 19 and 20 low 19 and 28 education 21 ( 28 education 22 1.27 28 education 23 , 25 - 24 1.05 25 - 25 - 26 1.54 25 - 27 ) 25 - 28 education 28 education 29 , 29 , 30 based 30 based 31 on 30 based 42 for 30 based 45 ) 31 on 37 test 32 the 37 test 33 χ 35 2 33 χ 37 test 34 ( 35 2 35 2 36 ) 37 test 40 < 38 ( 40 < 39 p 40 < 40 < 41 0.05 42 for 44 comparisons 43 both 44 comparisons a similar pattern was observed when financial satisfaction was used as the ses measure . 0 ###LEFT-WALL### 3 pattern 0 ###LEFT-WALL### 5 observed 0 ###LEFT-WALL### 15 . 1 a 2 similar 1 a 3 pattern 2 similar 3 pattern 3 pattern 4 was 4 was 5 observed 5 observed 6 when 6 when 8 satisfaction 6 when 10 used 7 financial 8 satisfaction 8 satisfaction 9 was 9 was 10 used 10 used 11 as 11 as 14 measure 12 the 14 measure 13 ses 14 measure however , the pattern was attenuated when using 5 - year mortality from baseline . 0 ###LEFT-WALL### 4 pattern 0 ###LEFT-WALL### 6 attenuated 0 ###LEFT-WALL### 10 - 0 ###LEFT-WALL### 15 . 1 however 2 , 1 however 4 pattern 3 the 4 pattern 4 pattern 5 was 5 was 6 attenuated 6 attenuated 7 when 7 when 8 using 8 using 9 5 10 - 12 mortality 11 year 12 mortality 12 mortality 13 from 13 from 14 baseline conclusions : the use of srh as a single health measure in elderly adults may yield inconsistent results across different ses groups , especially when used as a predictor of a longer - term mortality . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 4 use 2 : 16 yield 3 the 4 use 4 use 5 of 4 use 15 may 5 of 6 srh 6 srh 7 as 6 srh 12 in 7 as 11 measure 8 a 11 measure 9 single 10 health 10 health 11 measure 12 in 14 adults 13 elderly 14 adults 15 may 16 yield 16 yield 18 results 16 yield 19 across 16 yield 25 when 17 inconsistent 18 results 19 across 22 groups 20 different 22 groups 21 ses 22 groups 23 , 24 especially 23 , 25 when 25 when 26 used 25 when 36 . 26 used 27 as 27 as 29 predictor 28 a 29 predictor 29 predictor 30 of 30 of 35 mortality 31 a 35 mortality 32 longer 33 - 32 longer 34 term 34 term 35 mortality this is true regardless of whether objective or subjective measures of ses are used , where both are important measures of ses in elderly adults . 0 ###LEFT-WALL### 1 this 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 26 . 1 this 2 is 2 is 3 true 3 true 5 of 3 true 16 where 3 true 23 in 4 regardless 5 of 5 of 6 whether 6 whether 10 measures 6 whether 14 used 7 objective 8 or 8 or 9 subjective 8 or 10 measures 10 measures 11 of 10 measures 13 are 11 of 12 ses 13 are 14 used 14 used 15 , 16 where 17 both 16 where 18 are 17 both 18 are 18 are 20 measures 19 important 20 measures 20 measures 21 of 21 of 22 ses 23 in 25 adults 24 elderly 25 adults objectives : the ultrastructural appearance of retinal capillaries can yield important information about disease mechanisms , but is not well characterised in human post [mortem] samples . 0 ###LEFT-WALL### 1 objectives 0 ###LEFT-WALL### 2 : 2 : 5 appearance 2 : 17 but 2 : 27 . 3 the 5 appearance 4 ultrastructural 5 appearance 5 appearance 6 of 5 appearance 17 but 6 of 8 capillaries 7 retinal 8 capillaries 9 can 10 yield 9 can 17 but 10 yield 12 information 10 yield 13 about 11 important 12 information 13 about 15 mechanisms 14 disease 15 mechanisms 16 , 17 but 17 but 18 is 18 is 19 not 18 is 20 well 20 well 21 characterised 21 characterised 22 in 22 in 26 samples 23 human 24 post 24 post 26 samples we therefore aimed to create a baseline for the appearance of capillaries and establish how this is influenced by post [mortem] fixation delays and donor age . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 27 . 1 we 13 and 2 therefore 3 aimed 3 aimed 4 to 3 aimed 5 create 3 aimed 13 and 4 to 5 create 5 create 7 baseline 5 create 8 for 6 a 7 baseline 8 for 10 appearance 9 the 10 appearance 10 appearance 11 of 11 of 12 capillaries 13 and 14 establish 14 establish 15 how 14 establish 19 by 15 how 16 this 15 how 18 influenced 16 this 17 is 17 is 18 influenced 19 by 24 and 20 post 22 fixation 22 fixation 23 delays 23 delays 24 and 24 and 26 age 25 donor 26 age methods : electron microscopy was used to characterise retinal capillaries in 20 anonymous donors ( with no known eye diseases ) of various ages and with various post [mortem] fixation delays . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 32 . 2 : 4 microscopy 2 : 6 used 2 : 25 and 3 electron 4 microscopy 4 microscopy 5 was 5 was 6 used 6 used 7 to 6 used 8 characterise 7 to 8 characterise 8 characterise 10 capillaries 9 retinal 10 capillaries 10 capillaries 11 in 10 capillaries 22 of 11 in 14 donors 12 20 14 donors 13 anonymous 14 donors 14 donors 16 with 15 ( 16 with 16 with 20 diseases 16 with 21 ) 17 no 20 diseases 18 known 19 eye 19 eye 20 diseases 22 of 24 ages 23 various 24 ages 25 and 30 fixation 25 and 31 delays 26 with 28 post 26 with 30 fixation 27 various 28 post 30 fixation 31 delays in addition , samples from six patients with conditions that are known to affect the retinal vasculature ( four cases of type 2 diabetes without diabetic retinopathy , one case of diabetic retinopathy and one case of macular telangiectasia type 2 ) were analysed . 0 ###LEFT-WALL### 4 samples 0 ###LEFT-WALL### 44 analysed 0 ###LEFT-WALL### 45 . 1 in 2 addition 1 in 3 , 1 in 4 samples 4 samples 5 from 4 samples 10 that 4 samples 11 are 4 samples 43 were 5 from 7 patients 6 six 7 patients 7 patients 8 with 8 with 9 conditions 10 that 11 are 11 are 12 known 12 known 13 to 12 known 14 affect 13 to 14 affect 14 affect 17 vasculature 15 the 17 vasculature 16 retinal 17 vasculature 17 vasculature 20 cases 18 ( 20 cases 19 four 20 cases 20 cases 21 of 20 cases 34 and 20 cases 42 ) 21 of 24 diabetes 22 type 24 diabetes 23 2 24 diabetes 24 diabetes 25 without 25 without 27 retinopathy 26 diabetic 27 retinopathy 28 , 34 and 29 one 30 case 30 case 31 of 30 case 34 and 31 of 33 retinopathy 32 diabetic 33 retinopathy 34 and 36 case 34 and 37 of 34 and 42 ) 35 one 36 case 37 of 40 type 38 macular 40 type 39 telangiectasia 40 type 40 type 41 2 43 were 44 analysed results : vacuoles were found in capillary basement membranes at the vessel - glia [interface] in all samples , from both the normal and disease cases . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 27 . 2 : 3 vacuoles 2 : 5 found 3 vacuoles 4 were 4 were 5 found 5 found 6 in 6 in 9 membranes 7 capillary 9 membranes 8 basement 9 membranes 9 membranes 10 at 9 membranes 20 from 10 at 12 vessel 11 the 12 vessel 12 vessel 14 glia 13 - 14 glia 14 glia 16 in 14 glia 19 , 16 in 18 samples 17 all 18 samples 20 from 24 and 21 both 24 and 22 the 23 normal 23 normal 24 and 24 and 26 cases 25 disease 26 cases vacuole frequency increased with donor age but was not influenced by post [mortem] fixation delays . 0 ###LEFT-WALL### 2 frequency 0 ###LEFT-WALL### 7 but 0 ###LEFT-WALL### 16 . 1 vacuole 2 frequency 2 frequency 7 but 3 increased 4 with 3 increased 7 but 4 with 6 age 5 donor 6 age 7 but 8 was 8 was 9 not 8 was 11 by 9 not 10 influenced 11 by 15 delays 12 post 15 delays 14 fixation 15 delays conclusion : vacuoles in the basement membrane are a normal feature [of] adult human retinal capillaries [and] do not indicate disease . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 3 vacuoles 2 : 8 are 2 : 22 . 3 vacuoles 4 in 3 vacuoles 8 are 4 in 7 membrane 5 the 7 membrane 6 basement 7 membrane 8 are 14 human 9 a 10 normal 9 a 14 human 10 normal 11 feature 11 feature 13 adult 13 adult 14 human 14 human 16 capillaries 14 human 20 indicate 15 retinal 16 capillaries 16 capillaries 18 do 18 do 19 not 18 do 20 indicate 20 indicate 21 disease their incidence increases with age and might be a contributing factor to late - onset pathologies of the retinal vasculature . 0 ###LEFT-WALL### 2 incidence 0 ###LEFT-WALL### 6 and 0 ###LEFT-WALL### 21 . 1 their 2 incidence 2 incidence 6 and 3 increases 4 with 3 increases 6 and 4 with 5 age 6 and 7 might 6 and 12 to 7 might 8 be 8 be 11 factor 9 a 11 factor 10 contributing 11 factor 12 to 16 pathologies 13 late 14 - 13 late 15 onset 15 onset 16 pathologies 16 pathologies 17 of 17 of 20 vasculature 18 the 20 vasculature 19 retinal 20 vasculature none none telomerases constitute a group of specialized ribonucleoprotein enzymes that remediate chromosomal shrinkage resulting from the " end [-] replication " problem . 0 ###LEFT-WALL### 1 none 0 ###LEFT-WALL### 8 specialized 0 ###LEFT-WALL### 24 . 1 none 3 telomerases 1 none 7 of 1 none 8 specialized 2 none 3 telomerases 3 telomerases 4 constitute 4 constitute 6 group 5 a 6 group 6 group 7 of 8 specialized 10 enzymes 9 ribonucleoprotein 10 enzymes 10 enzymes 11 that 10 enzymes 12 remediate 11 that 12 remediate 12 remediate 14 shrinkage 13 chromosomal 14 shrinkage 14 shrinkage 15 resulting 15 resulting 16 from 16 from 23 problem 17 the 18 " 17 the 23 problem 19 end 23 problem 21 replication 22 " 21 replication 23 problem defects in telomere length regulation are associated with several diseases as well as with aging and cancer . 0 ###LEFT-WALL### 1 defects 0 ###LEFT-WALL### 7 associated 0 ###LEFT-WALL### 18 . 1 defects 2 in 1 defects 6 are 2 in 5 regulation 3 telomere 4 length 4 length 5 regulation 6 are 7 associated 7 associated 8 with 7 associated 11 as 8 with 10 diseases 9 several 10 diseases 11 as 16 and 12 well 13 as 12 well 16 and 13 as 14 with 14 with 15 aging 16 and 17 cancer despite significant progress in understanding the roles of telomerase , the complete structure of the human telomerase enzyme bound to telomeric dna remains elusive , with the detailed molecular mechanism of telomere elongation still unknown . 0 ###LEFT-WALL### 13 structure 0 ###LEFT-WALL### 23 remains 1 despite 3 progress 1 despite 10 , 1 despite 13 structure 2 significant 3 progress 3 progress 4 in 3 progress 8 of 4 in 5 understanding 5 understanding 7 roles 6 the 7 roles 8 of 9 telomerase 11 the 13 structure 12 complete 13 structure 13 structure 14 of 13 structure 19 bound 13 structure 23 remains 14 of 18 enzyme 15 the 18 enzyme 16 human 17 telomerase 17 telomerase 18 enzyme 19 bound 20 to 20 to 22 dna 21 telomeric 22 dna 23 remains 24 elusive 24 elusive 26 with 25 , 26 with 26 with 30 mechanism 26 with 34 still 26 with 35 unknown 26 with 36 . 27 the 30 mechanism 28 detailed 30 mechanism 29 molecular 30 mechanism 30 mechanism 31 of 31 of 33 elongation 32 telomere 33 elongation by application of computational methods for distant homology detection , comparative modeling , and molecular docking , guided by available experimental data , we have generated a three [-] dimensional structural model of a partial telomerase elongation complex composed of three essential protein domains bound to a single - stranded telomeric dna sequence in the form of a heteroduplex with the template region of the human rna subunit , ter . 0 ###LEFT-WALL### 14 and 0 ###LEFT-WALL### 26 generated 0 ###LEFT-WALL### 71 . 1 by 2 application 1 by 14 and 2 application 3 of 3 of 5 methods 4 computational 5 methods 5 methods 6 for 6 for 8 homology 7 distant 8 homology 9 detection 10 , 10 , 12 modeling 10 , 14 and 11 comparative 12 modeling 13 , 14 and 14 and 15 molecular 14 and 16 docking 14 and 24 we 14 and 25 have 14 and 26 generated 16 docking 18 guided 17 , 18 guided 18 guided 19 by 18 guided 23 , 19 by 22 data 20 available 22 data 21 experimental 22 data 24 we 25 have 26 generated 32 model 26 generated 60 with 27 a 32 model 28 three 32 model 30 dimensional 32 model 31 structural 32 model 32 model 33 of 32 model 40 of 32 model 44 domains 32 model 45 bound 33 of 38 complex 34 a 35 partial 34 a 38 complex 35 partial 37 elongation 36 telomerase 37 elongation 37 elongation 38 complex 38 complex 39 composed 40 of 43 protein 41 three 43 protein 42 essential 43 protein 44 domains 45 bound 45 bound 46 to 46 to 53 sequence 47 a 48 single 47 a 53 sequence 48 single 49 - 48 single 53 sequence 50 stranded 53 sequence 51 telomeric 53 sequence 52 dna 53 sequence 53 sequence 54 in 54 in 56 form 55 the 56 form 56 form 57 of 57 of 59 heteroduplex 58 a 59 heteroduplex 60 with 63 region 60 with 70 ter 61 the 63 region 62 template 63 region 63 region 64 of 64 of 67 rna 65 the 67 rna 66 human 67 rna 68 subunit 69 , 68 subunit 70 ter this model provides a structural mechanism for the processivity of telomerase and offers new insights into elongation . 0 ###LEFT-WALL### 2 model 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 18 . 1 this 2 model 2 model 12 and 3 provides 6 mechanism 3 provides 12 and 4 a 5 structural 4 a 6 mechanism 5 structural 6 mechanism 6 mechanism 7 for 7 for 9 processivity 8 the 9 processivity 9 processivity 10 of 10 of 11 telomerase 12 and 13 offers 13 offers 15 insights 13 offers 16 into 14 new 15 insights 16 into 17 elongation we conclude that the rnadna heteroduplex is constrained by the telomerase ten domain through repeated extension cycles and that the ten domain controls the process by moving the template ahead one base at a time by translation and rotation of the double helix . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 conclude 0 ###LEFT-WALL### 44 . 1 we 2 conclude 2 conclude 18 and 3 that 5 rnadna 3 that 15 repeated 3 that 18 and 4 the 5 rnadna 5 rnadna 6 heteroduplex 5 rnadna 14 through 5 rnadna 15 repeated 6 heteroduplex 7 is 7 is 8 constrained 8 constrained 9 by 8 constrained 14 through 9 by 13 domain 10 the 13 domain 11 telomerase 13 domain 12 ten 13 domain 15 repeated 17 cycles 16 extension 17 cycles 18 and 19 that 19 that 22 domain 19 that 23 controls 20 the 22 domain 21 ten 22 domain 22 domain 23 controls 23 controls 25 process 24 the 25 process 25 process 26 by 26 by 27 moving 27 moving 29 template 28 the 29 template 29 template 30 ahead 29 template 38 and 29 template 43 helix 31 one 32 base 32 base 33 at 32 base 36 by 32 base 38 and 33 at 35 time 34 a 35 time 36 by 37 translation 38 and 39 rotation 38 and 40 of 38 and 43 helix 40 of 42 double 41 the 42 double the rna region directly following the template can bind complementarily to the newly synthesized telomeric dna , while the template itself is reused in the telomerase active site during the next reaction cycle . 0 ###LEFT-WALL### 3 region 0 ###LEFT-WALL### 9 bind 0 ###LEFT-WALL### 17 , 0 ###LEFT-WALL### 34 . 1 the 3 region 2 rna 3 region 3 region 5 following 3 region 8 can 4 directly 5 following 5 following 7 template 6 the 7 template 8 can 9 bind 9 bind 10 complementarily 9 bind 11 to 11 to 16 dna 12 the 16 dna 13 newly 14 synthesized 14 synthesized 16 dna 15 telomeric 16 dna 17 , 33 cycle 18 while 20 template 18 while 23 reused 18 while 33 cycle 19 the 20 template 20 template 22 is 21 itself 22 is 22 is 23 reused 23 reused 24 in 23 reused 29 during 24 in 28 site 25 the 28 site 26 telomerase 28 site 27 active 28 site 29 during 32 reaction 30 the 31 next 30 the 32 reaction this first structural model of the human telomerase enzyme provides many details of the molecular mechanism of telomerase and immediately provides an important target for rational drug design . 0 ###LEFT-WALL### 4 model 0 ###LEFT-WALL### 19 and 0 ###LEFT-WALL### 29 . 1 this 4 model 2 first 4 model 3 structural 4 model 4 model 5 of 4 model 19 and 5 of 9 enzyme 6 the 9 enzyme 7 human 9 enzyme 8 telomerase 9 enzyme 10 provides 12 details 10 provides 19 and 11 many 12 details 12 details 13 of 13 of 16 mechanism 14 the 16 mechanism 15 molecular 16 mechanism 16 mechanism 17 of 17 of 18 telomerase 19 and 21 provides 20 immediately 21 provides 21 provides 24 target 22 an 23 important 22 an 24 target 23 important 24 target 24 target 25 for 25 for 28 design 26 rational 27 drug 27 drug 28 design the small mammalian mitochondrial dna ( mtdna ) is very [gene] dense and encodes factors critical for oxidative phosphorylation . 0 ###LEFT-WALL### 5 dna 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 20 . 1 the 5 dna 2 small 5 dna 3 mammalian 5 dna 4 mitochondrial 5 dna 5 dna 7 mtdna 5 dna 13 and 6 ( 7 mtdna 7 mtdna 8 ) 9 is 12 dense 9 is 13 and 10 very 12 dense 13 and 14 encodes 13 and 15 factors 15 factors 16 critical 16 critical 17 for 17 for 19 phosphorylation 18 oxidative 19 phosphorylation mutations of mtdna cause a variety of human mitochondrial diseases and [are] also heavily implicated in age - associated disease and aging . 0 ###LEFT-WALL### 1 mutations 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 18 - 1 mutations 2 of 1 mutations 11 and 2 of 3 mtdna 4 cause 6 variety 4 cause 11 and 5 a 6 variety 6 variety 7 of 7 of 10 diseases 8 human 10 diseases 9 mitochondrial 10 diseases 11 and 15 implicated 11 and 16 in 13 also 15 implicated 14 heavily 15 implicated 16 in 17 age 18 - 21 and 18 - 23 . 19 associated 20 disease 20 disease 21 and 21 and 22 aging there has been considerable progress in our understanding of the role for mtdna mutations in human pathology during the last two decades [,] but important mechanisms in mitochondrial genetics remain to be explained at the molecular level . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 3 been 0 ###LEFT-WALL### 38 . 1 there 2 has 2 has 3 been 3 been 5 progress 4 considerable 5 progress 5 progress 6 in 5 progress 15 in 6 in 8 understanding 7 our 8 understanding 8 understanding 9 of 9 of 11 role 10 the 11 role 11 role 12 for 12 for 14 mutations 13 mtdna 14 mutations 15 in 17 pathology 16 human 17 pathology 17 pathology 18 during 17 pathology 21 two 17 pathology 32 be 17 pathology 33 explained 18 during 20 last 19 the 20 last 21 two 22 decades 21 two 31 to 21 two 32 be 22 decades 24 but 22 decades 27 in 22 decades 30 remain 24 but 26 mechanisms 25 important 26 mechanisms 27 in 29 genetics 28 mitochondrial 29 genetics 30 remain 31 to 33 explained 34 at 34 at 37 level 35 the 37 level 36 molecular 37 level in addition , mounting evidence suggests that most mtdna mutations may be generated by replication errors and not by accumulated damage . 0 ###LEFT-WALL### 4 mounting 0 ###LEFT-WALL### 6 suggests 0 ###LEFT-WALL### 22 . 1 in 2 addition 1 in 3 , 1 in 4 mounting 4 mounting 5 evidence 4 mounting 6 suggests 6 suggests 7 that 7 that 10 mutations 7 that 13 generated 8 most 9 mtdna 9 mtdna 10 mutations 10 mutations 11 may 11 may 12 be 12 be 13 generated 13 generated 17 and 14 by 16 errors 14 by 17 and 15 replication 16 errors 17 and 18 not 17 and 19 by 19 by 21 damage 20 accumulated 21 damage the older population is currently the fastest growing age group in the united states , and this trend is expected to continue for several decades . 0 ###LEFT-WALL### 3 population 0 ###LEFT-WALL### 22 continue 0 ###LEFT-WALL### 26 . 1 the 3 population 2 older 3 population 3 population 4 is 4 is 5 currently 4 is 7 fastest 6 the 7 fastest 7 fastest 8 growing 7 fastest 22 continue 8 growing 16 and 8 growing 19 is 9 age 10 group 10 group 11 in 10 group 16 and 11 in 14 states 12 the 14 states 13 united 14 states 15 , 16 and 16 and 18 trend 17 this 18 trend 19 is 20 expected 20 expected 21 to 20 expected 22 continue 21 to 22 continue 22 continue 23 for 23 for 25 decades 24 several 25 decades older individuals , in general , have a higher disease burden compared with younger adults and are the major users of medications , yet premarketing drug clinical trials have often excluded them even for the drugs that have high utility in this age group . 0 ###LEFT-WALL### 2 individuals 0 ###LEFT-WALL### 7 have 0 ###LEFT-WALL### 16 and 0 ###LEFT-WALL### 45 . 1 older 2 individuals 2 individuals 5 general 2 individuals 7 have 3 , 5 general 4 in 5 general 5 general 6 , 7 have 11 burden 7 have 13 with 8 a 11 burden 9 higher 10 disease 10 disease 11 burden 11 burden 12 compared 13 with 15 adults 14 younger 15 adults 16 and 17 are 16 and 31 excluded 17 are 20 users 17 are 21 of 17 are 24 yet 18 the 20 users 19 major 20 users 21 of 22 medications 23 , 24 yet 24 yet 28 trials 25 premarketing 26 drug 26 drug 28 trials 27 clinical 28 trials 28 trials 29 have 29 have 31 excluded 30 often 31 excluded 31 excluded 32 them 31 excluded 33 even 31 excluded 41 in 33 even 34 for 34 for 36 drugs 35 the 36 drugs 36 drugs 37 that 36 drugs 38 have 37 that 38 have 38 have 40 utility 39 high 40 utility 41 in 44 group 42 this 44 group 43 age 44 group extrapolation of clinical results from younger [to] older individuals does not provide adequate benefit [-] risk estimation , and the frequent need for dose adjustment in older patients from initially approved doses exemplifies the current lack of adequate clinical data in the elderly . 0 ###LEFT-WALL### 1 extrapolation 0 ###LEFT-WALL### 12 provide 0 ###LEFT-WALL### 19 and 0 ###LEFT-WALL### 44 . 1 extrapolation 2 of 1 extrapolation 5 from 1 extrapolation 10 does 2 of 4 results 3 clinical 4 results 5 from 9 individuals 6 younger 9 individuals 8 older 9 individuals 10 does 11 not 10 does 12 provide 12 provide 17 estimation 13 adequate 14 benefit 14 benefit 17 estimation 16 risk 17 estimation 18 , 19 and 19 and 22 need 19 and 33 exemplifies 20 the 22 need 21 frequent 22 need 22 need 23 for 22 need 33 exemplifies 23 for 25 adjustment 24 dose 25 adjustment 25 adjustment 26 in 26 in 28 patients 27 older 28 patients 28 patients 29 from 29 from 32 doses 30 initially 31 approved 31 approved 32 doses 33 exemplifies 36 lack 33 exemplifies 41 in 34 the 36 lack 35 current 36 lack 36 lack 37 of 37 of 40 data 38 adequate 40 data 39 clinical 40 data 41 in 43 elderly 42 the 43 elderly herein , we discuss the information gap for older individuals and the need for a better understanding of the effect of aging on drug responses . 0 ###LEFT-WALL### 1 herein 0 ###LEFT-WALL### 2 , 0 ###LEFT-WALL### 26 . 2 , 3 we 2 , 4 discuss 3 we 4 discuss 4 discuss 7 gap 4 discuss 8 for 4 discuss 14 for 5 the 7 gap 6 information 7 gap 8 for 11 and 9 older 10 individuals 10 individuals 11 and 11 and 13 need 12 the 13 need 14 for 17 understanding 15 a 17 understanding 16 better 17 understanding 17 understanding 18 of 17 understanding 21 of 18 of 20 effect 19 the 20 effect 21 of 22 aging 22 aging 23 on 23 on 25 responses 24 drug 25 responses we also present cases for future directions , urging the implementation of improved clinical trial designs using new and emerging pharmacokinetic and pharmacodynamic methods to allow the provision of evidence - based individualized treatment to this high drug use group . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 32 based 0 ###LEFT-WALL### 41 . 1 we 3 present 2 also 3 present 3 present 4 cases 3 present 5 for 5 for 7 directions 6 future 7 directions 7 directions 9 urging 7 directions 32 based 8 , 9 urging 9 urging 11 implementation 9 urging 17 using 9 urging 31 - 10 the 11 implementation 11 implementation 12 of 12 of 16 designs 13 improved 15 trial 14 clinical 15 trial 15 trial 16 designs 17 using 19 and 17 using 25 to 17 using 26 allow 18 new 19 and 19 and 24 methods 20 emerging 24 methods 21 pharmacokinetic 22 and 22 and 23 pharmacodynamic 22 and 24 methods 25 to 26 allow 26 allow 28 provision 27 the 28 provision 28 provision 29 of 29 of 30 evidence 32 based 34 treatment 33 individualized 34 treatment 34 treatment 35 to 35 to 40 group 36 this 40 group 37 high 40 group 38 drug 39 use 39 use 40 group recent research in the geography of health care moves beyond distributive concerns focusing more sensitively on the nature of health care settings . 0 ###LEFT-WALL### 2 research 0 ###LEFT-WALL### 9 moves 0 ###LEFT-WALL### 23 . 1 recent 2 research 2 research 3 in 2 research 9 moves 3 in 5 geography 4 the 5 geography 5 geography 6 of 6 of 8 care 7 health 8 care 9 moves 10 beyond 10 beyond 12 concerns 11 distributive 12 concerns 12 concerns 13 focusing 12 concerns 16 on 13 focusing 15 sensitively 14 more 15 sensitively 16 on 18 nature 17 the 18 nature 18 nature 19 of 19 of 22 settings 20 health 22 settings 21 care 22 settings as part of this , a growing number of studies explore the importance of individuals ' personal circumstances on their emplaced experiences and agency . 0 ###LEFT-WALL### 10 studies 0 ###LEFT-WALL### 11 explore 0 ###LEFT-WALL### 25 . 1 as 2 part 1 as 5 , 1 as 10 studies 2 part 3 of 3 of 4 this 6 a 8 number 7 growing 8 number 8 number 9 of 8 number 10 studies 9 of 10 studies 10 studies 11 explore 11 explore 13 importance 11 explore 19 on 12 the 13 importance 13 importance 14 of 14 of 18 circumstances 15 individuals 16 ' 16 ' 18 circumstances 17 personal 18 circumstances 19 on 23 and 20 their 22 experiences 21 emplaced 22 experiences 22 experiences 23 and 23 and 24 agency extending this line of inquiry , and drawing on ideas in emotional geographies , the current study [illustrates] how experiences and agency can be impacted profoundly [by] [needle] [phobia] . 0 ###LEFT-WALL### 16 current 0 ###LEFT-WALL### 17 study 0 ###LEFT-WALL### 30 . 1 extending 3 line 1 extending 9 on 1 extending 11 in 1 extending 14 , 1 extending 16 current 2 this 3 line 3 line 4 of 4 of 7 and 5 inquiry 7 and 6 , 7 and 7 and 8 drawing 9 on 10 ideas 11 in 13 geographies 12 emotional 13 geographies 15 the 16 current 16 current 17 study 17 study 19 how 19 how 21 and 19 how 25 impacted 20 experiences 21 and 21 and 22 agency 21 and 23 can 23 can 24 be 24 be 25 impacted 25 impacted 26 profoundly interviews [with] 11 self - identifying sufferers explore the physical , emotional , behavioral and spatial manifestations of their condition . 0 ###LEFT-WALL### 4 self 0 ###LEFT-WALL### 5 - 0 ###LEFT-WALL### 21 . 1 interviews 3 11 1 interviews 4 self 5 - 7 sufferers 5 - 8 explore 6 identifying 7 sufferers 7 sufferers 8 explore 8 explore 17 manifestations 9 the 17 manifestations 10 physical 11 , 10 physical 17 manifestations 12 emotional 13 , 12 emotional 17 manifestations 14 behavioral 15 and 15 and 16 spatial 15 and 17 manifestations 17 manifestations 18 of 18 of 20 condition 19 their 20 condition aims : arterial stiffening may lead to [hypertension] , greater left [ventricular] [after] - [load] and adverse clinical outcomes . 0 ###LEFT-WALL### 1 aims 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 9 , 0 ###LEFT-WALL### 20 . 1 aims 2 : 2 : 3 arterial 3 arterial 4 stiffening 3 arterial 7 to 4 stiffening 5 may 5 may 6 lead 6 lead 7 to 9 , 19 outcomes 10 greater 19 outcomes 11 left 16 and 14 - 16 and 16 and 17 adverse 16 and 19 outcomes 18 clinical 19 outcomes the underlying mechanisms influencing arterial elasticity may involve oxidative injury to the vessel wall . 0 ###LEFT-WALL### 3 mechanisms 0 ###LEFT-WALL### 8 involve 0 ###LEFT-WALL### 15 . 1 the 3 mechanisms 2 underlying 3 mechanisms 3 mechanisms 4 influencing 3 mechanisms 7 may 4 influencing 6 elasticity 5 arterial 6 elasticity 7 may 8 involve 8 involve 10 injury 8 involve 11 to 9 oxidative 10 injury 11 to 14 wall 12 the 14 wall 13 vessel 14 wall we sought to examine the relationship between novel markers of oxidative stress and arterial elastic properties in healthy humans . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 sought 0 ###LEFT-WALL### 20 . 1 we 2 sought 2 sought 3 to 2 sought 4 examine 3 to 4 examine 4 examine 6 relationship 4 examine 7 between 4 examine 17 in 5 the 6 relationship 7 between 13 and 8 novel 9 markers 9 markers 10 of 9 markers 13 and 10 of 12 stress 11 oxidative 12 stress 13 and 16 properties 14 arterial 16 properties 15 elastic 16 properties 17 in 19 humans 18 healthy 19 humans methods and results : we studied 169 subjects ( mean age 42.6 ± 14 years , 51.6 % male ) free [of] traditional cardiovascular risk factors . 0 ###LEFT-WALL### 3 results 0 ###LEFT-WALL### 4 : 1 methods 2 and 2 and 3 results 4 : 5 we 4 : 6 studied 4 : 16 , 4 : 27 . 5 we 6 studied 6 studied 8 subjects 7 169 8 subjects 8 subjects 15 years 9 ( 15 years 10 mean 11 age 11 age 15 years 12 42.6 13 ± 13 ± 15 years 14 14 15 years 15 years 16 , 16 , 26 factors 17 51.6 26 factors 18 % 26 factors 19 male 20 ) 19 male 26 factors 21 free 26 factors 23 traditional 26 factors 24 cardiovascular 26 factors 25 risk 26 factors indices of arterial stiffness and wave reflections measured included carotid - femoral pulse wave velocity ( pwv ) , augmentation index ( aix ) and pulse pressure amplification ( ppa ) . 0 ###LEFT-WALL### 25 and 0 ###LEFT-WALL### 32 . 1 indices 2 of 1 indices 5 and 2 of 4 stiffness 3 arterial 4 stiffness 5 and 7 reflections 5 and 8 measured 5 and 9 included 5 and 17 pwv 5 and 25 and 6 wave 7 reflections 9 included 10 carotid 11 - 17 pwv 12 femoral 17 pwv 13 pulse 14 wave 14 wave 15 velocity 15 velocity 17 pwv 16 ( 17 pwv 17 pwv 18 ) 17 pwv 21 index 17 pwv 24 ) 19 , 21 index 20 augmentation 21 index 21 index 23 aix 21 index 24 ) 22 ( 23 aix 23 aix 24 ) 25 and 30 ppa 26 pulse 27 pressure 27 pressure 28 amplification 28 amplification 30 ppa 29 ( 30 ppa 30 ppa 31 ) inflammation was assessed as hscrp and interleukin - 6 levels . 0 ###LEFT-WALL### 1 inflammation 0 ###LEFT-WALL### 3 assessed 0 ###LEFT-WALL### 8 - 1 inflammation 2 was 2 was 3 assessed 3 assessed 4 as 4 as 6 and 5 hscrp 6 and 6 and 7 interleukin 8 - 10 levels 8 - 11 . 9 6 10 levels the [non] [-] free radical marker of oxidative stress [,] cystine was significantly correlated with all arterial indices ; pwv ( r=0.38 , p<0.001 ) , aix ( r=0.35 , p<0.001 ) and ppa ( r= - 0.30 , p<0.001 ) . 0 ###LEFT-WALL### 6 marker 0 ###LEFT-WALL### 14 correlated 0 ###LEFT-WALL### 19 ; 0 ###LEFT-WALL### 42 . 1 the 6 marker 4 free 5 radical 5 radical 6 marker 6 marker 7 of 6 marker 11 cystine 6 marker 12 was 6 marker 14 correlated 7 of 9 stress 8 oxidative 9 stress 11 cystine 12 was 12 was 13 significantly 14 correlated 15 with 15 with 18 indices 16 all 18 indices 17 arterial 18 indices 19 ; 33 and 20 pwv 24 p<0.001 20 pwv 26 , 21 ( 24 p<0.001 22 r=0.38 23 , 22 r=0.38 24 p<0.001 24 p<0.001 25 ) 26 , 27 aix 26 , 33 and 27 aix 31 p<0.001 28 ( 31 p<0.001 29 r=0.35 30 , 29 r=0.35 31 p<0.001 31 p<0.001 32 ) 33 and 34 ppa 34 ppa 40 p<0.001 35 ( 40 p<0.001 36 r= 38 0.30 36 r= 40 p<0.001 37 - 38 0.30 38 0.30 39 , 40 p<0.001 41 ) its redox potential [,] was also associated with pwv ( r=0.22 , p=0.01 ) , while the free radical marker of oxidative stress droms was associated with aix ( r=0.25 , p<0.01 ) . 0 ###LEFT-WALL### 3 potential 0 ###LEFT-WALL### 7 associated 0 ###LEFT-WALL### 34 . 1 its 3 potential 2 redox 3 potential 3 potential 5 was 5 was 6 also 5 was 7 associated 7 associated 8 with 7 associated 16 while 8 with 9 pwv 9 pwv 13 p=0.01 10 ( 13 p=0.01 11 r=0.22 12 , 11 r=0.22 13 p=0.01 13 p=0.01 14 ) 15 , 16 while 16 while 20 marker 16 while 26 associated 16 while 33 ) 17 the 20 marker 18 free 20 marker 19 radical 20 marker 20 marker 21 of 20 marker 25 was 21 of 24 droms 22 oxidative 23 stress 23 stress 24 droms 25 was 26 associated 26 associated 27 with 27 with 28 aix 28 aix 30 r=0.25 28 aix 32 p<0.01 29 ( 30 r=0.25 30 r=0.25 31 , 31 , 32 p<0.01 32 p<0.01 33 ) after multivariate adjustment for age , gender , arterial pressure , height , weight , heart rate and crp , of these oxidative stress markers , only cystine remained independently associated with pwv ( p=0.03 ) , aix ( p=0.01 ) and ppa ( p=0.05 ) . 0 ###LEFT-WALL### 3 adjustment 0 ###LEFT-WALL### 31 associated 0 ###LEFT-WALL### 47 . 1 after 2 multivariate 1 after 3 adjustment 3 adjustment 4 for 3 adjustment 31 associated 4 for 18 and 5 age 6 , 6 , 7 gender 6 , 8 , 8 , 10 pressure 8 , 11 , 9 arterial 10 pressure 11 , 12 height 11 , 13 , 13 , 14 weight 13 , 15 , 15 , 17 rate 15 , 18 and 16 heart 17 rate 18 and 19 crp 18 and 27 only 18 and 29 remained 19 crp 21 of 20 , 21 of 21 of 25 markers 21 of 26 , 22 these 25 markers 23 oxidative 24 stress 24 stress 25 markers 27 only 28 cystine 28 cystine 29 remained 29 remained 30 independently 31 associated 32 with 32 with 42 and 33 pwv 35 p=0.03 33 pwv 37 , 34 ( 35 p=0.03 35 p=0.03 36 ) 37 , 38 aix 37 , 42 and 38 aix 40 p=0.01 39 ( 40 p=0.01 40 p=0.01 41 ) 42 and 43 ppa 42 and 45 p=0.05 44 ( 45 p=0.05 45 p=0.05 46 ) conclusions : in healthy subjects without confounding risk factors or significant systemic inflammation , a high cystine level , reflecting extracellular oxidant burden , is associated with increased arterial stiffness and wave reflections . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 10 or 0 ###LEFT-WALL### 34 . 1 conclusions 2 : 2 : 3 in 2 : 6 without 3 in 5 subjects 4 healthy 5 subjects 6 without 7 confounding 7 confounding 9 factors 8 risk 9 factors 10 or 13 inflammation 10 or 26 associated 11 significant 13 inflammation 12 systemic 13 inflammation 13 inflammation 18 level 13 inflammation 25 is 14 , 18 level 15 a 16 high 15 a 18 level 16 high 17 cystine 17 cystine 18 level 18 level 20 reflecting 18 level 24 , 19 , 20 reflecting 20 reflecting 23 burden 20 reflecting 24 , 21 extracellular 22 oxidant 22 oxidant 23 burden 25 is 26 associated 26 associated 27 with 27 with 31 and 27 with 33 reflections 28 increased 30 stiffness 29 arterial 30 stiffness 30 stiffness 31 and 31 and 32 wave this has implications for understanding the role of oxidant burden in pre - clinical vascular dysfunction . 0 ###LEFT-WALL### 1 this 0 ###LEFT-WALL### 2 has 0 ###LEFT-WALL### 17 . 1 this 2 has 2 has 3 implications 3 implications 4 for 4 for 5 understanding 5 understanding 7 role 5 understanding 11 in 6 the 7 role 7 role 8 of 8 of 10 burden 9 oxidant 10 burden 11 in 16 dysfunction 12 pre 13 - 12 pre 16 dysfunction 14 clinical 16 dysfunction 15 vascular 16 dysfunction in vivo detection of alzheimer 's disease ( ad ) neuropathology in living patients using positron emission tomography ( pet ) in conjunction with high affinity molecular imaging probes for β - amyloid ( aβ ) and tau has the potential to assist with early diagnosis , evaluation [of] disease progression , and assessment of therapeutic interventions . 0 ###LEFT-WALL### 3 detection 0 ###LEFT-WALL### 58 . 1 in 2 vivo 2 vivo 3 detection 3 detection 4 of 3 detection 11 neuropathology 3 detection 39 has 4 of 7 disease 5 alzheimer 6 's 6 's 7 disease 7 disease 9 ad 8 ( 9 ad 9 ad 10 ) 11 neuropathology 12 in 11 neuropathology 22 in 12 in 14 patients 13 living 14 patients 14 patients 15 using 15 using 18 tomography 16 positron 17 emission 17 emission 18 tomography 18 tomography 20 pet 19 ( 20 pet 20 pet 21 ) 22 in 37 and 23 conjunction 24 with 23 conjunction 37 and 24 with 26 affinity 25 high 26 affinity 26 affinity 28 imaging 26 affinity 29 probes 26 affinity 30 for 26 affinity 35 aβ 27 molecular 28 imaging 28 imaging 29 probes 30 for 33 amyloid 31 β 32 - 31 β 33 amyloid 34 ( 35 aβ 35 aβ 36 ) 37 and 38 tau 39 has 41 potential 39 has 44 with 40 the 41 potential 41 potential 42 to 41 potential 43 assist 42 to 43 assist 44 with 53 and 45 early 46 diagnosis 46 diagnosis 47 , 47 , 51 progression 47 , 53 and 48 evaluation 51 progression 50 disease 51 progression 52 , 53 and 53 and 54 assessment 53 and 55 of 55 of 57 interventions 56 therapeutic 57 interventions animal models of ad are valuable for exploring [the] in vivo binding of these probes , particularly their selectivity for specific neuropathologies , but prior pet experiments in transgenic mice have yielded conflicting results . 0 ###LEFT-WALL### 2 models 0 ###LEFT-WALL### 5 are 0 ###LEFT-WALL### 24 but 0 ###LEFT-WALL### 35 . 1 animal 2 models 2 models 3 of 2 models 5 are 3 of 4 ad 5 are 6 valuable 6 valuable 7 for 7 for 8 exploring 8 exploring 11 vivo 8 exploring 12 binding 10 in 11 vivo 12 binding 13 of 13 of 15 probes 14 these 15 probes 15 probes 19 selectivity 16 , 17 particularly 16 , 19 selectivity 18 their 19 selectivity 19 selectivity 20 for 19 selectivity 23 , 20 for 22 neuropathologies 21 specific 22 neuropathologies 23 , 24 but 24 but 27 experiments 24 but 32 yielded 25 prior 27 experiments 26 pet 27 experiments 27 experiments 28 in 27 experiments 31 have 28 in 30 mice 29 transgenic 30 mice 31 have 32 yielded 32 yielded 34 results 33 conflicting 34 results in this work , we utilized micropet imaging in a transgenic rat model of brain aβ deposition to assess [ f - 18 ]fddnp binding profiles in relation to age - associated accumulation of neuropathology . 0 ###LEFT-WALL### 5 we 0 ###LEFT-WALL### 6 utilized 0 ###LEFT-WALL### 36 . 1 in 3 work 1 in 4 , 1 in 5 we 2 this 3 work 5 we 6 utilized 6 utilized 7 micropet 7 micropet 8 imaging 8 imaging 9 in 8 imaging 33 accumulation 9 in 13 model 10 a 11 transgenic 10 a 13 model 11 transgenic 13 model 12 rat 13 model 13 model 14 of 14 of 17 deposition 15 brain 17 deposition 16 aβ 17 deposition 17 deposition 18 to 17 deposition 19 assess 17 deposition 26 profiles 18 to 19 assess 20 [ 26 profiles 21 f 22 - 22 - 23 18 22 - 25 binding 24 ]fddnp 25 binding 25 binding 26 profiles 26 profiles 27 in 26 profiles 29 to 26 profiles 31 - 27 in 28 relation 29 to 30 age 32 associated 33 accumulation 33 accumulation 34 of 34 of 35 neuropathology cross - sectional and longitudinal imaging demonstrated that [ f - 18 ]fddnp binding in the hippocampus and frontal cortex progressively increases from 9 to 18 months of age and parallels age - associated aβ accumulation . 0 ###LEFT-WALL### 1 cross 0 ###LEFT-WALL### 34 associated 0 ###LEFT-WALL### 37 . 1 cross 4 and 1 cross 34 associated 2 - 4 and 3 sectional 4 and 4 and 5 longitudinal 4 and 6 imaging 4 and 7 demonstrated 4 and 18 and 4 and 33 - 6 imaging 7 demonstrated 7 demonstrated 8 that 9 [ 18 and 10 f 11 - 11 - 12 18 11 - 13 ]fddnp 13 ]fddnp 14 binding 13 ]fddnp 15 in 13 ]fddnp 18 and 15 in 17 hippocampus 16 the 17 hippocampus 18 and 20 cortex 18 and 30 and 18 and 33 - 19 frontal 20 cortex 21 progressively 22 increases 22 increases 23 from 22 increases 30 and 23 from 27 months 24 9 25 to 25 to 26 18 25 to 27 months 27 months 28 of 28 of 29 age 30 and 31 parallels 31 parallels 32 age 34 associated 36 accumulation 35 aβ 36 accumulation specificity of in [vivo] [[] f - 18 ]fddnp binding was assessed by naproxen pretreatment , which reversibly blocked [[] f - 18 ]fddnp binding to aβ aggregrates . 0 ###LEFT-WALL### 1 specificity 0 ###LEFT-WALL### 12 assessed 0 ###LEFT-WALL### 16 , 0 ###LEFT-WALL### 29 . 1 specificity 2 of 1 specificity 11 was 2 of 3 in 3 in 9 ]fddnp 6 f 7 - 7 - 8 18 7 - 9 ]fddnp 9 ]fddnp 10 binding 11 was 12 assessed 12 assessed 13 by 13 by 15 pretreatment 14 naproxen 15 pretreatment 16 , 17 which 16 , 19 blocked 17 which 19 blocked 18 reversibly 19 blocked 19 blocked 24 ]fddnp 19 blocked 26 to 21 f 22 - 22 - 23 18 22 - 24 ]fddnp 24 ]fddnp 25 binding 26 to 28 aggregrates 27 aβ 28 aggregrates both [ f - 18 ]fddnp micropet imaging and neuropathological analyses revealed decreased aβ burden after intracranial anti - aβ antibody administration . 0 ###LEFT-WALL### 1 both 0 ###LEFT-WALL### 13 decreased 0 ###LEFT-WALL### 23 . 1 both 13 decreased 2 [ 12 revealed 3 f 4 - 4 - 5 18 4 - 8 imaging 6 ]fddnp 7 micropet 7 micropet 8 imaging 8 imaging 9 and 9 and 11 analyses 9 and 12 revealed 10 neuropathological 11 analyses 12 revealed 13 decreased 13 decreased 15 burden 13 decreased 16 after 14 aβ 15 burden 16 after 22 administration 17 intracranial 21 antibody 18 anti 19 - 18 anti 21 antibody 20 aβ 21 antibody 21 antibody 22 administration the combination of this [non] [-] invasive imaging method and robust animal model of brain aβ accumulation allows for future longitudinal [in] [vivo] assessments of potential therapeutics for ad that target aβ production , aggregation , [and/or] clearance . 0 ###LEFT-WALL### 2 combination 0 ###LEFT-WALL### 18 allows 1 the 2 combination 2 combination 3 of 2 combination 10 and 2 combination 13 model 2 combination 14 of 2 combination 18 allows 3 of 8 imaging 4 this 8 imaging 7 invasive 8 imaging 9 method 10 and 10 and 12 animal 10 and 13 model 11 robust 12 animal 14 of 17 accumulation 15 brain 17 accumulation 16 aβ 17 accumulation 18 allows 19 for 18 allows 33 production 19 for 24 assessments 20 future 24 assessments 21 longitudinal 24 assessments 24 assessments 25 of 24 assessments 30 that 24 assessments 31 target 25 of 27 therapeutics 26 potential 27 therapeutics 27 therapeutics 28 for 28 for 29 ad 30 that 31 target 31 target 32 aβ 33 production 35 aggregation 33 production 38 clearance 34 , 35 aggregation 35 aggregation 36 , 36 , 38 clearance 38 clearance 39 . these results corroborate previous analyses of [[] f - 18 ]fddnp pet imaging in clinical populations . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 corroborate 0 ###LEFT-WALL### 17 . 1 these 2 results 2 results 3 corroborate 3 corroborate 5 analyses 4 previous 5 analyses 5 analyses 6 of 5 analyses 10 18 5 analyses 13 imaging 6 of 8 f 9 - 10 18 10 18 11 ]fddnp 11 ]fddnp 12 pet 12 pet 13 imaging 13 imaging 14 in 14 in 16 populations 15 clinical 16 populations it has been demonstrated that exogenous expression of a combination of transcription factors can reprogram differentiated cells such as fibroblasts and keratinocytes into what have been termed induced pluripotent [stem] ( ips ) cells . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 4 demonstrated 1 it 2 has 2 has 3 been 3 been 4 demonstrated 4 demonstrated 5 that 5 that 7 expression 5 that 21 and 6 exogenous 7 expression 7 expression 8 of 7 expression 14 can 8 of 10 combination 9 a 10 combination 10 combination 11 of 11 of 13 factors 12 transcription 13 factors 14 can 21 and 15 reprogram 17 cells 15 reprogram 21 and 16 differentiated 17 cells 17 cells 19 as 18 such 19 as 19 as 20 fibroblasts 21 and 22 keratinocytes 21 and 23 into 21 and 29 pluripotent 23 into 24 what 24 what 25 have 25 have 26 been 26 been 27 termed 28 induced 29 pluripotent 29 pluripotent 34 cells 31 ( 34 cells 32 ips 33 ) 32 ips 34 cells 34 cells 35 . these ips cells are capable of differentiating into all the tissue lineages when placed in the right environment and [,] in the case of mouse cells , can generate chimeric mice and be transmitted through the germline . 0 ###LEFT-WALL### 3 cells 0 ###LEFT-WALL### 4 are 0 ###LEFT-WALL### 27 , 0 ###LEFT-WALL### 38 . 1 these 3 cells 2 ips 3 cells 3 cells 4 are 4 are 5 capable 5 capable 6 of 5 capable 13 when 6 of 7 differentiating 7 differentiating 8 into 8 into 9 all 9 all 10 the 9 all 12 lineages 10 the 12 lineages 11 tissue 12 lineages 13 when 14 placed 14 placed 19 and 15 in 18 environment 15 in 19 and 16 the 18 environment 17 right 18 environment 19 and 21 in 21 in 23 case 22 the 23 case 23 case 24 of 24 of 26 cells 25 mouse 26 cells 27 , 32 and 28 can 29 generate 28 can 32 and 29 generate 31 mice 30 chimeric 31 mice 32 and 33 be 33 be 34 transmitted 34 transmitted 35 through 35 through 37 germline 36 the 37 germline safer and more efficient methods of reprogramming are rapidly being developed . 0 ###LEFT-WALL### 5 methods 0 ###LEFT-WALL### 8 are 0 ###LEFT-WALL### 12 . 1 safer 2 and 2 and 3 more 2 and 5 methods 4 efficient 5 methods 5 methods 6 of 5 methods 8 are 6 of 7 reprogramming 8 are 10 being 9 rapidly 10 being 10 being 11 developed clearly , ips cells present a number of exciting possibilities , including disease modeling and therapy . 0 ###LEFT-WALL### 4 cells 0 ###LEFT-WALL### 5 present 1 clearly 2 , 1 clearly 4 cells 3 ips 4 cells 4 cells 5 present 5 present 10 possibilities 5 present 12 including 6 a 7 number 7 number 8 of 7 number 10 possibilities 8 of 10 possibilities 9 exciting 10 possibilities 11 , 12 including 12 including 15 and 12 including 17 . 13 disease 14 modeling 14 modeling 15 and 15 and 16 therapy a major question is whether the nuclei of ips cells are truly rejuvenated or whether they might retain some of the marks of aging from the cells from which they were derived . 0 ###LEFT-WALL### 3 question 0 ###LEFT-WALL### 33 . 1 a 3 question 2 major 3 question 3 question 4 is 4 is 5 whether 5 whether 14 or 5 whether 32 derived 6 the 7 nuclei 7 nuclei 8 of 7 nuclei 14 or 8 of 9 ips 9 ips 10 cells 9 ips 11 are 9 ips 13 rejuvenated 10 cells 11 are 11 are 12 truly 14 or 15 whether 14 or 16 they 14 or 24 aging 14 or 25 from 14 or 32 derived 16 they 17 might 17 might 18 retain 18 retain 19 some 19 some 20 of 20 of 22 marks 21 the 22 marks 22 marks 23 of 23 of 24 aging 25 from 27 cells 25 from 30 they 25 from 31 were 26 the 27 cells 27 cells 28 from 28 from 29 which 30 they 31 were one measure of cellular aging is the telomere . 0 ###LEFT-WALL### 2 measure 0 ###LEFT-WALL### 6 is 0 ###LEFT-WALL### 9 . 1 one 2 measure 2 measure 3 of 2 measure 6 is 3 of 5 aging 4 cellular 5 aging 6 is 8 telomere 7 the 8 telomere in this regard , recent studies have demonstrated that telomeres in ips cells may be rejuvenated . 0 ###LEFT-WALL### 6 studies 0 ###LEFT-WALL### 8 demonstrated 0 ###LEFT-WALL### 17 . 1 in 3 regard 1 in 4 , 1 in 6 studies 2 this 3 regard 5 recent 6 studies 6 studies 7 have 7 have 8 demonstrated 8 demonstrated 9 that 9 that 10 telomeres 9 that 16 rejuvenated 10 telomeres 11 in 10 telomeres 14 may 11 in 13 cells 12 ips 13 cells 14 may 15 be 15 be 16 rejuvenated they are not only elongated by reactivated telomerase but they are also epigenetically modified to be similar but not identical to embryonic stem cells . 0 ###LEFT-WALL### 1 they 0 ###LEFT-WALL### 5 elongated 0 ###LEFT-WALL### 9 but 0 ###LEFT-WALL### 25 . 1 they 2 are 2 are 3 not 2 are 5 elongated 4 only 5 elongated 5 elongated 6 by 6 by 8 telomerase 7 reactivated 8 telomerase 9 but 10 they 9 but 14 modified 10 they 11 are 11 are 12 also 11 are 14 modified 13 epigenetically 14 modified 14 modified 15 to 15 to 16 be 16 be 18 but 17 similar 18 but 18 but 19 not 18 but 20 identical 19 not 20 identical 20 identical 21 to 21 to 24 cells 22 embryonic 23 stem 23 stem 24 cells upon differentiation , the derivative cells turn down telomerase , the telomeres begin to shorten again , and the telomeres and the genome are returned to an epigenetic state that is similar to normal differentiated somatic cells . 0 ###LEFT-WALL### 6 cells 0 ###LEFT-WALL### 7 turn 0 ###LEFT-WALL### 10 , 0 ###LEFT-WALL### 38 . 1 upon 2 differentiation 1 upon 3 , 1 upon 6 cells 4 the 6 cells 5 derivative 6 cells 6 cells 7 turn 7 turn 8 down 8 down 9 telomerase 10 , 12 telomeres 10 , 13 begin 10 , 18 and 11 the 12 telomeres 12 telomeres 13 begin 13 begin 14 to 13 begin 15 shorten 14 to 15 shorten 15 shorten 16 again 17 , 18 and 18 and 21 and 18 and 25 returned 19 the 20 telomeres 20 telomeres 21 and 21 and 23 genome 21 and 24 are 22 the 23 genome 24 are 25 returned 25 returned 26 to 26 to 29 state 27 an 28 epigenetic 27 an 29 state 28 epigenetic 29 state 29 state 30 that 29 state 31 is 30 that 31 is 31 is 32 similar 32 similar 33 to 33 to 37 cells 34 normal 37 cells 35 differentiated 37 cells 36 somatic 37 cells while these preliminary telomere findings are promising , the overall genomic integrity of reprogrammed cells may still be problematic and further studies are needed to examine the safety and feasibility of using ips cells in regenerative medicine applications . 0 ###LEFT-WALL### 12 integrity 0 ###LEFT-WALL### 20 and 0 ###LEFT-WALL### 39 . 1 while 5 findings 1 while 6 are 1 while 8 , 1 while 12 integrity 2 these 5 findings 3 preliminary 4 telomere 4 telomere 5 findings 5 findings 6 are 6 are 7 promising 9 the 12 integrity 10 overall 12 integrity 11 genomic 12 integrity 12 integrity 13 of 12 integrity 16 may 13 of 15 cells 14 reprogrammed 15 cells 16 may 20 and 17 still 20 and 18 be 19 problematic 18 be 20 and 20 and 26 examine 21 further 22 studies 22 studies 23 are 23 are 24 needed 24 needed 25 to 25 to 26 examine 26 examine 29 and 27 the 28 safety 28 safety 29 and 29 and 30 feasibility 29 and 31 of 29 and 35 in 31 of 32 using 32 using 34 cells 33 ips 34 cells 35 in 38 applications 36 regenerative 37 medicine 37 medicine 38 applications background : the profession of respiratory therapy ( rt ) continues to grow both in [number] , due to population growth and an ever [-] increasing aging population , and scope of practice , due to both new and expanded roles and responsibilities in divergent areas of clinical practice . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 4 profession 2 : 11 continues 3 the 4 profession 4 profession 5 of 4 profession 11 continues 5 of 7 therapy 6 respiratory 7 therapy 7 therapy 9 rt 8 ( 9 rt 9 rt 10 ) 11 continues 12 to 11 continues 17 , 11 continues 18 due 12 to 13 grow 13 grow 14 both 13 grow 15 in 18 due 19 to 19 to 30 and 20 population 21 growth 21 growth 22 and 22 and 28 population 22 and 29 , 22 and 30 and 23 an 28 population 24 ever 26 increasing 26 increasing 28 population 27 aging 28 population 30 and 31 scope 30 and 32 of 32 of 33 practice 33 practice 42 and 34 , 42 and 35 due 36 to 35 due 42 and 36 to 39 and 37 both 39 and 38 new 39 and 39 and 41 roles 40 expanded 41 roles 42 and 43 responsibilities 42 and 44 in 42 and 47 of 42 and 50 . 44 in 46 areas 45 divergent 46 areas 47 of 49 practice 48 clinical 49 practice instructional technology , including distance learning , will probably play a key role in training , educating , and assessing rt students to meet the increasing demand for practitioners . 0 ###LEFT-WALL### 2 technology 0 ###LEFT-WALL### 24 meet 0 ###LEFT-WALL### 30 . 1 instructional 2 technology 2 technology 4 including 2 technology 8 will 3 , 4 including 4 including 6 learning 4 including 7 , 5 distance 6 learning 8 will 10 play 9 probably 10 play 10 play 13 role 10 play 14 in 10 play 23 to 11 a 13 role 12 key 13 role 14 in 19 and 15 training 16 , 16 , 17 educating 16 , 19 and 18 , 19 and 19 and 22 students 20 assessing 22 students 21 rt 22 students 23 to 24 meet 24 meet 27 demand 25 the 27 demand 26 increasing 27 demand 27 demand 28 for 28 for 29 practitioners objective : to assess current uses of distance learning and opinions concerning the appropriate use of distance education in rt education programs nationwide . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 22 programs 0 ###LEFT-WALL### 24 . 1 objective 2 : 2 : 3 to 2 : 4 assess 3 to 4 assess 4 assess 6 uses 4 assess 19 in 5 current 6 uses 6 uses 7 of 6 uses 12 concerning 6 uses 16 of 7 of 10 and 8 distance 9 learning 9 learning 10 and 10 and 11 opinions 12 concerning 15 use 13 the 15 use 14 appropriate 15 use 16 of 18 education 17 distance 18 education 19 in 20 rt 20 rt 21 education 20 rt 22 programs 21 education 22 programs 22 programs 23 nationwide methods : a 13 [-] item on [-] line [survey] was designed to collect information about the frequency of use of various types of distance education typically utilized in rt education programs . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 6 item 2 : 12 designed 2 : 33 . 3 a 6 item 4 13 6 item 6 item 9 line 6 item 11 was 7 on 9 line 11 was 12 designed 12 designed 13 to 12 designed 14 collect 13 to 14 collect 14 collect 15 information 14 collect 16 about 14 collect 29 in 16 about 18 frequency 17 the 18 frequency 18 frequency 19 of 18 frequency 21 of 19 of 20 use 21 of 26 education 22 various 23 types 23 types 24 of 23 types 26 education 24 of 26 education 25 distance 26 education 26 education 28 utilized 27 typically 28 utilized 29 in 32 programs 30 rt 31 education 31 education 32 programs the survey was sent to directors of 343 committee on accreditation for respiratory care accredited programs of rt education that offer entry - level or advanced courses of study . 0 ###LEFT-WALL### 2 survey 0 ###LEFT-WALL### 4 sent 0 ###LEFT-WALL### 23 - 0 ###LEFT-WALL### 30 . 1 the 2 survey 2 survey 3 was 3 was 4 sent 4 sent 5 to 4 sent 10 on 4 sent 16 programs 5 to 6 directors 6 directors 7 of 7 of 9 committee 8 343 9 committee 10 on 11 accreditation 11 accreditation 12 for 11 accreditation 15 accredited 12 for 14 care 13 respiratory 14 care 16 programs 17 of 16 programs 20 that 16 programs 21 offer 17 of 19 education 18 rt 19 education 20 that 21 offer 21 offer 22 entry 23 - 27 courses 24 level 25 or 25 or 26 advanced 25 or 27 courses 27 courses 28 of 28 of 29 study results : the response rate was 50 % ( 169 respondents ) . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 5 rate 2 : 6 was 2 : 13 . 3 the 5 rate 4 response 5 rate 5 rate 6 was 6 was 8 % 7 50 8 % 8 % 11 respondents 9 ( 11 respondents 10 169 11 respondents 11 respondents 12 ) fifty - two percent of the respondents indicated that their courses included some form of on - line learning component . 0 ###LEFT-WALL### 1 fifty 0 ###LEFT-WALL### 2 - 2 - 4 percent 2 - 17 - 3 two 4 percent 4 percent 5 of 5 of 7 respondents 6 the 7 respondents 7 respondents 8 indicated 7 respondents 9 that 7 respondents 16 on 9 that 11 courses 9 that 12 included 10 their 11 courses 11 courses 12 included 12 included 14 form 13 some 14 form 14 form 15 of 15 of 16 on 17 - 20 component 17 - 21 . 18 line 20 component 19 learning 20 component most directors anticipated that the distance composition of their course offerings will remain unchanged or increase in the near future . 0 ###LEFT-WALL### 2 directors 0 ###LEFT-WALL### 15 or 0 ###LEFT-WALL### 21 . 1 most 2 directors 2 directors 15 or 3 anticipated 4 that 3 anticipated 15 or 4 that 7 composition 4 that 13 remain 5 the 7 composition 6 distance 7 composition 7 composition 8 of 7 composition 12 will 8 of 11 offerings 9 their 11 offerings 10 course 11 offerings 12 will 13 remain 13 remain 14 unchanged 15 or 16 increase 16 increase 17 in 17 in 20 future 18 the 20 future 19 near 20 future conclusions : our results indicate that , while distance education plays an important supportive role in rt education , there is still a preference for face - to [-] face instruction and internet - facilitated courses among program directors . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 4 results 2 : 7 , 3 our 4 results 4 results 5 indicate 5 indicate 6 that 7 , 19 , 8 while 10 education 8 while 19 , 9 distance 10 education 11 plays 15 role 11 plays 19 , 12 an 13 important 12 an 15 role 13 important 15 role 14 supportive 15 role 15 role 16 in 16 in 18 education 17 rt 18 education 19 , 30 face 20 there 21 is 21 is 22 still 21 is 24 preference 21 is 25 for 23 a 24 preference 25 for 26 face 26 face 28 to 27 - 28 to 28 to 30 face 30 face 32 and 31 instruction 32 and 32 and 33 internet 32 and 36 courses 34 - 36 courses 35 facilitated 36 courses 36 courses 37 among 36 courses 40 . 37 among 39 directors 38 program 39 directors program directors continue to view the laboratory and clinical settings as hands - on environments that require instructor supervision in order for students to demonstrate proficiency and critical thinking skills . 0 ###LEFT-WALL### 2 directors 0 ###LEFT-WALL### 3 continue 1 program 2 directors 2 directors 3 continue 3 continue 4 to 3 continue 5 view 4 to 5 view 5 view 8 and 6 the 7 laboratory 7 laboratory 8 and 8 and 10 settings 9 clinical 10 settings 10 settings 11 as 11 as 12 hands 12 hands 14 on 13 - 14 on 14 on 15 environments 14 on 31 . 15 environments 16 that 15 environments 17 require 16 that 17 require 17 require 19 supervision 17 require 22 for 17 require 24 to 17 require 25 demonstrate 18 instructor 19 supervision 19 supervision 20 in 20 in 21 order 22 for 23 students 24 to 25 demonstrate 25 demonstrate 27 and 26 proficiency 27 and 27 and 30 skills 28 critical 29 thinking 29 thinking 30 skills when used appropriately , distance learning may be an efficient and effective approach to address the many barriers to education faced by the health workforce in general , including budget constraints , overloaded schedules , the need [for] [on] - the [-] job learning opportunities , and lack of access . 1 when 2 used 1 when 5 distance 3 appropriately 4 , 3 appropriately 5 distance 5 distance 6 learning 5 distance 7 may 7 may 8 be 8 be 13 approach 8 be 19 to 9 an 13 approach 10 efficient 11 and 11 and 12 effective 11 and 13 approach 13 approach 14 to 13 approach 15 address 14 to 15 address 15 address 18 barriers 16 the 17 many 17 many 18 barriers 19 to 20 education 20 education 21 faced 20 education 22 by 20 education 26 in 22 by 25 workforce 23 the 25 workforce 24 health 25 workforce 26 in 34 schedules 27 general 31 constraints 27 general 32 , 27 general 34 schedules 28 , 31 constraints 29 including 30 budget 30 budget 31 constraints 31 constraints 32 , 33 overloaded 34 schedules 34 schedules 37 need 34 schedules 43 job 35 , 37 need 36 the 37 need 37 need 40 - 40 - 43 job 41 the 43 job 43 job 44 learning 43 job 51 . 44 learning 47 and 45 opportunities 47 and 46 , 47 and 47 and 48 lack 47 and 51 . 48 lack 49 of 49 of 50 access background : fall prevention interventions for community [-] dwelling older adults have been found to reduce falls in some research studies . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 22 . 2 : 4 prevention 2 : 17 falls 3 fall 4 prevention 4 prevention 5 interventions 4 prevention 16 reduce 4 prevention 17 falls 5 interventions 6 for 5 interventions 12 have 6 for 11 adults 7 community 9 dwelling 9 dwelling 11 adults 10 older 11 adults 12 have 13 been 13 been 14 found 14 found 15 to 15 to 16 reduce 17 falls 18 in 18 in 21 studies 19 some 21 studies 20 research 21 studies however , wider implementation of fall prevention activities in routine care has yielded mixed results . 0 ###LEFT-WALL### 4 implementation 0 ###LEFT-WALL### 13 yielded 0 ###LEFT-WALL### 16 . 1 however 2 , 1 however 4 implementation 3 wider 4 implementation 4 implementation 5 of 4 implementation 12 has 5 of 8 activities 6 fall 8 activities 7 prevention 8 activities 8 activities 9 in 9 in 11 care 10 routine 11 care 12 has 13 yielded 13 yielded 15 results 14 mixed 15 results we implemented a theory [-] driven program to improve care for [falls] at our veterans affairs healthcare facility . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 implemented 0 ###LEFT-WALL### 19 . 1 we 2 implemented 2 implemented 7 program 2 implemented 13 at 3 a 7 program 4 theory 6 driven 6 driven 7 program 7 program 8 to 7 program 11 for 8 to 9 improve 9 improve 10 care 9 improve 11 for 13 at 18 facility 14 our 18 facility 15 veterans 16 affairs 16 affairs 18 facility 17 healthcare 18 facility the first project arising from this program used a nurse advice telephone line to identify patients ' risk factors [for] [falls] and to triage patients to appropriate services . 0 ###LEFT-WALL### 3 project 0 ###LEFT-WALL### 8 used 0 ###LEFT-WALL### 29 . 1 the 3 project 2 first 3 project 3 project 4 arising 3 project 8 used 4 arising 5 from 5 from 7 program 6 this 7 program 8 used 13 line 8 used 14 to 8 used 22 and 9 a 13 line 10 nurse 13 line 11 advice 13 line 12 telephone 13 line 14 to 22 and 15 identify 19 factors 15 identify 22 and 16 patients 17 ' 17 ' 19 factors 18 risk 19 factors 22 and 27 appropriate 23 to 24 triage 24 triage 25 patients 24 triage 26 to 26 to 27 appropriate 27 appropriate 28 services here we report the formative evaluation of this project . 0 ###LEFT-WALL### 2 we 0 ###LEFT-WALL### 3 report 0 ###LEFT-WALL### 10 . 1 here 2 we 2 we 3 report 3 report 6 evaluation 4 the 6 evaluation 5 formative 6 evaluation 6 evaluation 7 of 7 of 9 project 8 this 9 project methods : to evaluate the intervention [we] : 1 ) interviewed patient and employee stakeholders , 2 ) reviewed participating patients ' electronic health record data and 3 [ )(abstracted information from meeting minutes . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 15 stakeholders 2 : 19 reviewed 2 : 27 and 2 : 35 . 3 to 4 evaluate 3 to 10 ) 3 to 15 stakeholders 4 evaluate 6 intervention 4 evaluate 8 : 5 the 6 intervention 6 intervention 8 : 8 : 9 1 11 interviewed 15 stakeholders 12 patient 13 and 13 and 14 employee 13 and 15 stakeholders 15 stakeholders 17 2 15 stakeholders 19 reviewed 16 , 17 2 17 2 18 ) 19 reviewed 26 data 20 participating 21 patients 21 patients 22 ' 22 ' 26 data 23 electronic 24 health 24 health 26 data 25 record 26 data 27 and 28 3 27 and 30 )(abstracted 28 3 30 )(abstracted 30 )(abstracted 31 information 31 information 32 from 32 from 33 meeting 33 meeting 34 minutes we describe the implementation process , including whether the project was implemented according to plan ; identify barriers and facilitators to implementation ; [and] assess the incremental benefit to the quality of health care for fall prevention received by patients in the project . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 describe 0 ###LEFT-WALL### 16 ; 0 ###LEFT-WALL### 44 . 1 we 2 describe 2 describe 5 process 2 describe 7 including 3 the 5 process 4 implementation 5 process 6 , 7 including 7 including 8 whether 7 including 13 according 7 including 14 to 7 including 16 ; 8 whether 10 project 8 whether 11 was 9 the 10 project 10 project 11 was 11 was 12 implemented 14 to 15 plan 16 ; 17 identify 16 ; 23 ; 17 identify 19 and 17 identify 21 to 18 barriers 19 and 19 and 20 facilitators 21 to 22 implementation 23 ; 25 assess 25 assess 28 benefit 25 assess 38 received 26 the 28 benefit 27 incremental 28 benefit 28 benefit 29 to 28 benefit 38 received 29 to 31 quality 30 the 31 quality 31 quality 32 of 32 of 34 care 33 health 34 care 34 care 35 for 35 for 37 prevention 36 fall 37 prevention 38 received 39 by 38 received 41 in 39 by 40 patients 41 in 43 project 42 the 43 project we also estimate the cost of developing the pilot project . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 estimate 0 ###LEFT-WALL### 11 . 1 we 3 estimate 2 also 3 estimate 3 estimate 5 cost 4 the 5 cost 5 cost 6 of 6 of 7 developing 7 developing 10 project 8 the 10 project 9 pilot 10 project results : the project underwent multiple changes over its life span , including the addition of an option to mail patients educational materials about falls . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 4 project 2 : 5 underwent 2 : 12 , 2 : 26 . 3 the 4 project 4 project 5 underwent 5 underwent 7 changes 5 underwent 8 over 6 multiple 7 changes 8 over 11 span 9 its 11 span 10 life 11 span 12 , 13 including 12 , 25 falls 13 including 15 addition 13 including 25 falls 14 the 15 addition 15 addition 16 of 16 of 18 option 17 an 18 option 18 option 19 to 18 option 20 mail 19 to 20 mail 20 mail 23 materials 20 mail 24 about 21 patients 23 materials 22 educational 23 materials during the project 's lifespan , 113 patients were considered for inclusion and 35 participated . 0 ###LEFT-WALL### 8 patients 0 ###LEFT-WALL### 10 considered 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 16 . 1 during 5 lifespan 1 during 6 , 1 during 8 patients 2 the 3 project 3 project 4 's 4 's 5 lifespan 7 113 8 patients 8 patients 9 were 9 were 10 considered 10 considered 11 for 11 for 12 inclusion 13 and 14 35 13 and 15 participated 14 35 15 participated patient and employee interviews suggested support for the project , but revealed that transportation to medical care was a major barrier in following up on fall risks identified by [nurse] telephone triage . 0 ###LEFT-WALL### 1 patient 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 33 . 2 and 4 interviews 2 and 32 triage 3 employee 4 interviews 4 interviews 11 but 5 suggested 6 support 5 suggested 7 for 5 suggested 11 but 7 for 9 project 8 the 9 project 10 , 11 but 11 but 12 revealed 12 revealed 14 transportation 12 revealed 18 was 13 that 14 transportation 14 transportation 15 to 14 transportation 18 was 15 to 17 care 16 medical 17 care 18 was 21 barrier 19 a 21 barrier 20 major 21 barrier 21 barrier 22 in 21 barrier 25 on 21 barrier 27 risks 21 barrier 32 triage 22 in 23 following 23 following 24 up 25 on 26 fall 27 risks 28 identified 27 risks 32 triage 28 identified 31 telephone 29 by 31 telephone medical record review showed that the project enhanced usual medical care with respect to home safety counseling . 0 ###LEFT-WALL### 3 review 0 ###LEFT-WALL### 4 showed 0 ###LEFT-WALL### 18 . 1 medical 2 record 2 record 3 review 3 review 4 showed 4 showed 5 that 5 that 7 project 5 that 8 enhanced 6 the 7 project 7 project 8 enhanced 8 enhanced 11 care 9 usual 11 care 10 medical 11 care 11 care 12 with 11 care 14 to 11 care 17 counseling 12 with 13 respect 14 to 15 home 15 home 16 safety 16 safety 17 counseling we discontinued the program after 18 months due to staffing limitations and competing priorities . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 discontinued 0 ###LEFT-WALL### 15 . 1 we 2 discontinued 2 discontinued 4 program 3 the 4 program 4 program 5 after 4 program 8 due 5 after 7 months 6 18 7 months 8 due 9 to 9 to 10 staffing 10 staffing 12 and 11 limitations 12 and 12 and 14 priorities 13 competing 14 priorities we estimated a cost of $ 9194 for meeting time to develop the project . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 estimated 0 ###LEFT-WALL### 15 . 1 we 2 estimated 2 estimated 4 cost 3 a 4 cost 4 cost 5 of 4 cost 8 for 5 of 6 $ 6 $ 7 9194 8 for 9 meeting 9 meeting 10 time 10 time 11 to 10 time 12 develop 11 to 12 develop 12 develop 14 project 13 the 14 project conclusions : the project appeared feasible at its outset but could not be sustained past the first cycle of evaluation due to insufficient resources and a waning of local leadership support due to competing national priorities . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 4 project 2 : 10 but 2 : 37 . 3 the 4 project 4 project 10 but 5 appeared 6 feasible 5 appeared 10 but 6 feasible 7 at 7 at 9 outset 8 its 9 outset 10 but 11 could 11 could 12 not 11 could 13 be 13 be 14 sustained 14 sustained 15 past 14 sustained 33 to 15 past 18 cycle 16 the 17 first 16 the 18 cycle 18 cycle 19 of 19 of 31 support 20 evaluation 31 support 21 due 22 to 21 due 25 and 22 to 24 resources 23 insufficient 24 resources 25 and 27 waning 25 and 31 support 26 a 27 waning 27 waning 28 of 28 of 30 leadership 29 local 30 leadership 32 due 33 to 33 to 36 priorities 34 competing 36 priorities 35 national 36 priorities future projects will need both front - level staff commitment and prolonged high - level leadership involvement to thrive . 0 ###LEFT-WALL### 1 future 0 ###LEFT-WALL### 2 projects 0 ###LEFT-WALL### 7 - 1 future 2 projects 2 projects 4 need 3 will 4 need 4 need 5 both 4 need 6 front 5 both 6 front 7 - 11 and 7 - 20 . 8 level 10 commitment 8 level 11 and 9 staff 10 commitment 11 and 12 prolonged 12 prolonged 17 involvement 12 prolonged 18 to 13 high 14 - 13 high 15 level 15 level 17 involvement 16 leadership 17 involvement 18 to 19 thrive background : with the ongoing demographic shift , the quality of life and health promotion among older individuals are becoming [increasingly] important . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 8 , 0 ###LEFT-WALL### 23 . 1 background 2 : 2 : 3 with 3 with 7 shift 4 the 7 shift 5 ongoing 7 shift 6 demographic 7 shift 8 , 13 and 8 , 19 are 9 the 10 quality 10 quality 11 of 10 quality 13 and 11 of 12 life 13 and 15 promotion 13 and 16 among 13 and 19 are 14 health 15 promotion 16 among 18 individuals 17 older 18 individuals 19 are 20 becoming 20 becoming 22 important recent research suggests that sense of coherence positively affects quality of life . 0 ###LEFT-WALL### 2 research 0 ###LEFT-WALL### 3 suggests 0 ###LEFT-WALL### 13 . 1 recent 2 research 2 research 3 suggests 3 suggests 4 that 4 that 5 sense 4 that 9 affects 5 sense 6 of 5 sense 9 affects 6 of 7 coherence 8 positively 9 affects 9 affects 10 quality 10 quality 11 of 11 of 12 life hence , a valid and reliable measurement of sense of coherence is pivotal . 0 ###LEFT-WALL### 7 measurement 0 ###LEFT-WALL### 12 is 0 ###LEFT-WALL### 14 . 1 hence 2 , 1 hence 7 measurement 3 a 7 measurement 4 valid 5 and 5 and 6 reliable 5 and 7 measurement 7 measurement 8 of 7 measurement 12 is 8 of 9 sense 9 sense 10 of 10 of 11 coherence 12 is 13 pivotal the 13 - item orientation to life questionnaire ( olq - 13 ) can be used to measure sense of coherence . 0 ###LEFT-WALL### 2 13 0 ###LEFT-WALL### 16 used 0 ###LEFT-WALL### 22 . 1 the 2 13 2 13 5 orientation 2 13 14 can 3 - 5 orientation 4 item 5 orientation 5 orientation 6 to 5 orientation 13 ) 6 to 10 olq 7 life 8 questionnaire 8 questionnaire 10 olq 9 ( 10 olq 10 olq 12 13 11 - 12 13 12 13 13 ) 14 can 15 be 15 be 16 used 16 used 17 to 16 used 18 measure 17 to 18 measure 18 measure 19 sense 19 sense 20 of 20 of 21 coherence the purpose of the present study is to assess the psychometric properties , validity , and reliability , of the olq - 13 in community - dwelling individuals , aged 65 and older . 0 ###LEFT-WALL### 2 purpose 0 ###LEFT-WALL### 34 . 1 the 2 purpose 2 purpose 3 of 2 purpose 7 is 3 of 6 study 4 the 6 study 5 present 6 study 7 is 8 to 7 is 9 assess 8 to 9 assess 9 assess 16 and 9 assess 32 and 10 the 12 properties 11 psychometric 12 properties 12 properties 13 , 13 , 14 validity 13 , 16 and 15 , 16 and 16 and 17 reliability 16 and 19 of 16 and 28 individuals 18 , 19 of 19 of 25 community 19 of 26 - 20 the 25 community 21 olq 25 community 22 - 23 13 23 13 24 in 24 in 25 community 26 - 28 individuals 27 dwelling 28 individuals 28 individuals 29 , 30 aged 31 65 30 aged 32 and 32 and 33 older methods : the olq - 13 scale was administered as part of a healthy aging project for [non] - institutionalized people aged 65 years and older . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 4 olq 2 : 22 aged 2 : 27 . 3 the 4 olq 4 olq 6 13 4 olq 7 scale 4 olq 8 was 5 - 6 13 6 13 7 scale 8 was 9 administered 9 administered 10 as 9 administered 17 for 10 as 11 part 11 part 12 of 12 of 16 project 13 a 14 healthy 13 a 16 project 14 healthy 16 project 15 aging 16 project 17 for 19 - 19 - 21 people 20 institutionalized 21 people 21 people 22 aged 22 aged 25 and 23 65 24 years 24 years 25 and 25 and 26 older internal consistency and reliability were assessed by means [of] [inter] - [item] and test - halves correlations and cronbach 's alpha . 0 ###LEFT-WALL### 1 internal 0 ###LEFT-WALL### 16 halves 0 ###LEFT-WALL### 22 . 1 internal 3 and 1 internal 5 were 1 internal 6 assessed 1 internal 16 halves 2 consistency 3 and 3 and 4 reliability 3 and 5 were 6 assessed 7 by 7 by 13 and 8 means 13 and 11 - 13 and 13 and 14 test 13 and 15 - 16 halves 18 and 17 correlations 18 and 18 and 21 alpha 19 cronbach 20 's 20 's 21 alpha construct validity was explored using cluster analysis and exploratory factor analysis ( n = 703 ) and tested using confirmatory factor analysis on a separate subset of individuals ( n = 658 ) . 0 ###LEFT-WALL### 2 validity 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 34 . 1 construct 2 validity 2 validity 17 and 3 was 4 explored 3 was 17 and 4 explored 5 using 4 explored 14 = 5 using 11 analysis 6 cluster 7 analysis 7 analysis 8 and 8 and 9 exploratory 8 and 10 factor 10 factor 11 analysis 12 ( 14 = 13 n 14 = 14 = 15 703 14 = 16 ) 17 and 18 tested 17 and 19 using 17 and 22 analysis 19 using 20 confirmatory 21 factor 22 analysis 22 analysis 23 on 22 analysis 27 of 22 analysis 31 = 23 on 26 subset 24 a 26 subset 25 separate 26 subset 27 of 28 individuals 29 ( 31 = 30 n 31 = 31 = 32 658 31 = 33 ) item face validity was investigated by means of 12 semi - structured interviews . 0 ###LEFT-WALL### 3 validity 0 ###LEFT-WALL### 5 investigated 0 ###LEFT-WALL### 14 . 1 item 3 validity 2 face 3 validity 3 validity 4 was 4 was 5 investigated 5 investigated 6 by 6 by 7 means 7 means 8 of 8 of 13 interviews 9 12 13 interviews 10 semi 11 - 10 semi 13 interviews 12 structured 13 interviews the psychometric properties of the proposed olq - 11 , obtained by deleting the two items , were better . 0 ###LEFT-WALL### 3 properties 0 ###LEFT-WALL### 18 were 0 ###LEFT-WALL### 20 . 1 the 3 properties 2 psychometric 3 properties 3 properties 4 of 3 properties 18 were 4 of 7 olq 5 the 7 olq 6 proposed 7 olq 7 olq 9 11 7 olq 11 obtained 8 - 9 11 9 11 10 , 10 , 11 obtained 11 obtained 12 by 11 obtained 17 , 12 by 13 deleting 13 deleting 16 items 14 the 15 two 15 two 16 items 18 were 19 better in particular , the interpretation [of] exploratory factor solution improved . 0 ###LEFT-WALL### 9 solution 0 ###LEFT-WALL### 10 improved 0 ###LEFT-WALL### 11 . 1 in 2 particular 2 particular 3 , 2 particular 9 solution 4 the 9 solution 5 interpretation 9 solution 7 exploratory 8 factor 8 factor 9 solution 9 solution 10 improved whereas the underlying theoretical constructs could not be linked to the exploratory analyses of olq - 13 , this was to some extent possible in olq - 11 . 0 ###LEFT-WALL### 5 constructs 0 ###LEFT-WALL### 9 linked 0 ###LEFT-WALL### 16 - 1 whereas 3 underlying 1 whereas 5 constructs 2 the 3 underlying 4 theoretical 5 constructs 5 constructs 6 could 6 could 7 not 6 could 8 be 8 be 9 linked 9 linked 10 to 10 to 13 analyses 11 the 13 analyses 12 exploratory 13 analyses 13 analyses 14 of 14 of 15 olq 16 - 17 13 16 - 18 , 16 - 29 . 18 , 19 this 18 , 20 was 18 , 27 - 19 this 20 was 20 was 21 to 20 was 24 possible 21 to 23 extent 22 some 23 extent 24 possible 25 in 25 in 26 olq 27 - 28 11 the superior validity of olq - 11 over olq - [13] was supported by the better model fit in the confirmatory factor analysis . 0 ###LEFT-WALL### 3 validity 0 ###LEFT-WALL### 13 supported 0 ###LEFT-WALL### 24 . 1 the 3 validity 2 superior 3 validity 3 validity 4 of 3 validity 12 was 4 of 5 olq 5 olq 7 11 6 - 7 11 7 11 8 over 7 11 10 - 8 over 9 olq 12 was 13 supported 13 supported 14 by 13 supported 18 fit 14 by 17 model 15 the 17 model 16 better 17 model 18 fit 19 in 19 in 23 analysis 20 the 23 analysis 21 confirmatory 23 analysis 22 factor 23 analysis conclusions : the present mixed - method study suggests the proposed olq - 11 as a more suitable instrument for measuring sense of coherence than the olq - 13 in a population of ageing individuals . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 6 - 0 ###LEFT-WALL### 36 . 1 conclusions 2 : 2 : 4 present 3 the 4 present 4 present 5 mixed 6 - 8 study 6 - 9 suggests 6 - 28 - 7 method 8 study 8 study 9 suggests 9 suggests 12 olq 10 the 12 olq 11 proposed 12 olq 12 olq 14 11 13 - 14 11 14 11 15 as 14 11 20 for 14 11 28 - 15 as 19 instrument 16 a 19 instrument 17 more 18 suitable 18 suitable 19 instrument 20 for 21 measuring 21 measuring 22 sense 21 measuring 25 than 22 sense 23 of 23 of 24 coherence 25 than 27 olq 26 the 27 olq 28 - 29 13 29 13 30 in 29 13 33 of 30 in 32 population 31 a 32 population 33 of 35 individuals 34 ageing 35 individuals this study confirms that the validity and reliability of olq - 13 may differ substantially in different populations . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 confirms 0 ###LEFT-WALL### 11 - 1 this 2 study 2 study 3 confirms 3 confirms 7 and 4 that 7 and 5 the 6 validity 6 validity 7 and 7 and 8 reliability 7 and 9 of 9 of 10 olq 11 - 12 13 11 - 14 differ 11 - 19 . 12 13 13 may 13 may 14 differ 14 differ 15 substantially 14 differ 16 in 16 in 18 populations 17 different 18 populations purpose : to [identify] [and] compare perceptions of the geriatric care environment among nurses in three different urban hospital types in one health authority in a midwestern canadian province . 0 ###LEFT-WALL### 1 purpose 0 ###LEFT-WALL### 2 : 2 : 3 to 2 : 6 compare 2 : 30 . 3 to 6 compare 6 compare 7 perceptions 6 compare 13 among 6 compare 15 in 6 compare 21 in 7 perceptions 8 of 8 of 12 environment 9 the 12 environment 10 geriatric 11 care 11 care 12 environment 13 among 14 nurses 15 in 20 types 16 three 20 types 17 different 19 hospital 18 urban 19 hospital 19 hospital 20 types 21 in 24 authority 22 one 24 authority 23 health 24 authority 24 authority 25 in 25 in 29 province 26 a 29 province 27 midwestern 29 province 28 canadian 29 province design : the geriatric institutional assessment profile developed by the nurses improving healthsystem elders ( niche ) program was administered to staff in eight urban hospitals between 2005 and 2006 : two geriatric - chronic care hospitals , four community hospitals , and two tertiary hospitals . 0 ###LEFT-WALL### 1 design 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 47 . 2 : 7 profile 2 : 31 : 3 the 7 profile 4 geriatric 5 institutional 5 institutional 6 assessment 6 assessment 7 profile 7 profile 8 developed 8 developed 9 by 8 developed 21 to 8 developed 23 in 9 by 11 nurses 10 the 11 nurses 11 nurses 12 improving 11 nurses 20 administered 12 improving 13 healthsystem 12 improving 19 was 12 improving 20 administered 13 healthsystem 14 elders 13 healthsystem 18 program 13 healthsystem 19 was 14 elders 16 niche 14 elders 18 program 15 ( 16 niche 16 niche 17 ) 21 to 22 staff 23 in 26 hospitals 24 eight 26 hospitals 25 urban 26 hospitals 26 hospitals 27 between 27 between 29 and 28 2005 29 and 29 and 30 2006 31 : 43 and 32 two 37 hospitals 33 geriatric 34 - 33 geriatric 36 care 35 chronic 36 care 36 care 37 hospitals 37 hospitals 38 , 38 , 41 hospitals 38 , 43 and 39 four 41 hospitals 40 community 41 hospitals 42 , 43 and 43 and 46 hospitals 44 two 46 hospitals 45 tertiary 46 hospitals the study focused on 1,189 nurses who completed the survey ( n= 298 for geriatric - chronic care hospitals ; n= 387 for community hospitals , n= 504 for tertiary hospitals ) . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 focused 0 ###LEFT-WALL### 20 ; 0 ###LEFT-WALL### 21 n= 0 ###LEFT-WALL### 33 . 1 the 2 study 2 study 3 focused 3 focused 4 on 4 on 6 nurses 5 1,189 6 nurses 6 nurses 7 who 6 nurses 8 completed 7 who 8 completed 8 completed 10 survey 9 the 10 survey 10 survey 12 n= 11 ( 12 n= 12 n= 13 298 12 n= 14 for 12 n= 20 ; 14 for 19 hospitals 15 geriatric 16 - 15 geriatric 18 care 17 chronic 18 care 18 care 19 hospitals 20 ; 21 n= 21 n= 22 387 22 387 23 for 23 for 25 hospitals 24 community 25 hospitals 25 hospitals 27 n= 26 , 27 n= 27 n= 28 504 27 n= 29 for 27 n= 32 ) 29 for 31 hospitals 30 tertiary 31 hospitals methods : analyses focused on items related to the concept of the geriatric nursing practice environment , including a composite measure of overall perceptions and three subscales ( institutional values regarding older adults and staff , resource availability , and capacity for collaboration ) . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 45 . 1 methods 2 : 2 : 3 analyses 3 analyses 4 focused 3 analyses 7 related 3 analyses 8 to 3 analyses 18 including 4 focused 5 on 5 on 6 items 8 to 10 concept 9 the 10 concept 10 concept 11 of 11 of 16 environment 12 the 16 environment 13 geriatric 14 nursing 14 nursing 15 practice 15 practice 16 environment 17 , 18 including 18 including 40 and 18 including 42 for 18 including 44 ) 19 a 20 composite 19 a 21 measure 20 composite 21 measure 21 measure 22 of 21 measure 40 and 22 of 25 and 23 overall 24 perceptions 24 perceptions 25 and 25 and 27 subscales 25 and 34 and 26 three 27 subscales 28 ( 34 and 29 institutional 30 values 30 values 31 regarding 30 values 34 and 31 regarding 33 adults 32 older 33 adults 34 and 35 staff 34 and 38 availability 34 and 39 , 36 , 38 availability 37 resource 38 availability 38 availability 39 , 40 and 41 capacity 42 for 43 collaboration nurses ' perceptions of the extent to which facilities supported the provision of aging - [sensitive] or aging - relevant care to older adults and their families was also examined . 0 ###LEFT-WALL### 17 or 0 ###LEFT-WALL### 19 - 0 ###LEFT-WALL### 31 . 1 nurses 2 ' 2 ' 3 perceptions 3 perceptions 4 of 3 perceptions 13 of 3 perceptions 17 or 4 of 6 extent 4 of 9 facilities 4 of 10 supported 5 the 6 extent 6 extent 7 to 7 to 8 which 9 facilities 10 supported 10 supported 12 provision 11 the 12 provision 13 of 14 aging 15 - 17 or 17 or 18 aging 19 - 20 relevant 19 - 28 was 20 relevant 28 was 21 care 22 to 21 care 28 was 22 to 25 and 23 older 24 adults 24 adults 25 and 25 and 27 families 26 their 27 families 28 was 29 also 28 was 30 examined univariate analysis of variance was performed to determine significant group differences among nurses in the three hospital types . 0 ###LEFT-WALL### 2 analysis 0 ###LEFT-WALL### 6 performed 0 ###LEFT-WALL### 19 . 1 univariate 2 analysis 2 analysis 3 of 2 analysis 5 was 3 of 4 variance 5 was 6 performed 6 performed 7 to 6 performed 14 in 7 to 8 determine 8 determine 11 differences 8 determine 12 among 9 significant 10 group 10 group 11 differences 12 among 13 nurses 14 in 18 types 15 the 16 three 16 three 18 types 17 hospital 18 types findings : perceptions of the geriatric nurse practice environment ( both in terms of the composite scale and the three subscales ) were least positive among nurses in community hospitals relative to the other two hospital types . 0 ###LEFT-WALL### 1 findings 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 38 . 2 : 3 perceptions 2 : 23 were 3 perceptions 4 of 3 perceptions 11 both 3 perceptions 23 were 4 of 9 environment 5 the 9 environment 6 geriatric 7 nurse 7 nurse 8 practice 8 practice 9 environment 10 ( 11 both 11 both 12 in 11 both 22 ) 12 in 13 terms 13 terms 14 of 14 of 18 and 15 the 17 scale 16 composite 17 scale 17 scale 18 and 18 and 21 subscales 19 the 20 three 20 three 21 subscales 23 were 25 positive 24 least 25 positive 25 positive 26 among 26 among 27 nurses 27 nurses 28 in 27 nurses 31 relative 28 in 30 hospitals 29 community 30 hospitals 31 relative 32 to 32 to 37 types 33 the 34 other 34 other 35 two 35 two 37 types 36 hospital 37 types perceptions in tertiary hospitals were significantly more positive than those in community hospitals in terms of institutional values and resource availability , [albeit] not capacity for collaboration . 0 ###LEFT-WALL### 1 perceptions 0 ###LEFT-WALL### 5 were 1 perceptions 2 in 1 perceptions 5 were 2 in 4 hospitals 3 tertiary 4 hospitals 5 were 8 positive 6 significantly 7 more 7 more 8 positive 8 positive 9 than 9 than 19 and 10 those 11 in 10 those 19 and 11 in 13 hospitals 12 community 13 hospitals 13 hospitals 14 in 14 in 15 terms 15 terms 16 of 16 of 18 values 17 institutional 18 values 19 and 21 availability 19 and 25 capacity 20 resource 21 availability 22 , 24 not 22 , 25 capacity 25 capacity 26 for 25 capacity 28 . 26 for 27 collaboration perceptions were most positive in the geriatric - chronic care hospitals . 0 ###LEFT-WALL### 1 perceptions 0 ###LEFT-WALL### 2 were 0 ###LEFT-WALL### 12 . 1 perceptions 2 were 2 were 4 positive 3 most 4 positive 4 positive 5 in 5 in 11 hospitals 6 the 11 hospitals 7 geriatric 8 - 7 geriatric 10 care 9 chronic 10 care 10 care 11 hospitals perceptions of aging [-] sensitive care delivery were also less positive in community [and] tertiary hospitals , relative to geriatric - chronic care hospitals ; perceptions in community [and] tertiary hospitals did not differ from each other . 0 ###LEFT-WALL### 1 perceptions 0 ###LEFT-WALL### 8 were 0 ###LEFT-WALL### 25 ; 0 ###LEFT-WALL### 38 . 1 perceptions 2 of 1 perceptions 8 were 2 of 3 aging 3 aging 7 delivery 5 sensitive 6 care 6 care 7 delivery 8 were 9 also 8 were 11 positive 10 less 11 positive 11 positive 12 in 12 in 16 hospitals 13 community 16 hospitals 15 tertiary 16 hospitals 16 hospitals 18 relative 17 , 18 relative 18 relative 19 to 18 relative 25 ; 19 to 24 hospitals 20 geriatric 21 - 20 geriatric 23 care 22 chronic 23 care 23 care 24 hospitals 25 ; 26 perceptions 25 ; 34 differ 26 perceptions 27 in 26 perceptions 32 did 27 in 31 hospitals 28 community 31 hospitals 30 tertiary 31 hospitals 32 did 33 not 32 did 34 differ 34 differ 35 from 35 from 37 other 36 each 37 other this research highlights the importance of the hospital setting in understanding nurses ' ability to provide quality geriatric care . 0 ###LEFT-WALL### 2 research 0 ###LEFT-WALL### 3 highlights 0 ###LEFT-WALL### 20 . 1 this 2 research 2 research 3 highlights 3 highlights 5 importance 4 the 5 importance 5 importance 6 of 6 of 8 hospital 7 the 8 hospital 8 hospital 9 setting 8 hospital 11 understanding 9 setting 10 in 11 understanding 14 ability 12 nurses 13 ' 13 ' 14 ability 14 ability 15 to 14 ability 16 provide 15 to 16 provide 16 provide 19 care 17 quality 19 care 18 geriatric 19 care clinical relevance : enhancing the quality of care for older patients requires an understanding of the challenges and obstacles experienced by nurses . 0 ###LEFT-WALL### 2 relevance 0 ###LEFT-WALL### 3 : 1 clinical 2 relevance 3 : 4 enhancing 3 : 12 requires 3 : 23 . 4 enhancing 6 quality 4 enhancing 9 for 4 enhancing 12 requires 5 the 6 quality 6 quality 7 of 7 of 8 care 9 for 11 patients 10 older 11 patients 12 requires 14 understanding 12 requires 21 by 13 an 14 understanding 14 understanding 15 of 15 of 18 and 16 the 17 challenges 17 challenges 18 and 18 and 19 obstacles 18 and 20 experienced 21 by 22 nurses assessing their perceptions of the care environment they work in , therefore , becomes a key issue in targeting policy and programs . 0 ###LEFT-WALL### 1 assessing 0 ###LEFT-WALL### 21 and 0 ###LEFT-WALL### 23 . 1 assessing 3 perceptions 1 assessing 21 and 2 their 3 perceptions 3 perceptions 4 of 4 of 7 environment 5 the 7 environment 6 care 7 environment 7 environment 8 they 7 environment 9 work 8 they 9 work 9 work 10 in 11 , 12 therefore 12 therefore 13 , 12 therefore 14 becomes 14 becomes 17 issue 14 becomes 18 in 14 becomes 21 and 15 a 17 issue 16 key 17 issue 18 in 19 targeting 19 targeting 20 policy 21 and 22 programs none objective : to compare the safety and efficacy of two fractional carbon dioxide ( co ( 2 ) ) laser devices for the treatment of photodamaged facial skin . 0 ###LEFT-WALL### 1 none 0 ###LEFT-WALL### 21 laser 0 ###LEFT-WALL### 30 . 1 none 2 objective 1 none 3 : 1 none 21 laser 2 objective 3 : 3 : 4 to 4 to 5 compare 5 compare 8 and 6 the 8 and 7 safety 8 and 8 and 9 efficacy 8 and 10 of 10 of 14 dioxide 11 two 13 carbon 12 fractional 13 carbon 13 carbon 14 dioxide 14 dioxide 16 co 15 ( 16 co 16 co 18 2 16 co 20 ) 17 ( 18 2 18 2 19 ) 21 laser 22 devices 21 laser 23 for 23 for 25 treatment 24 the 25 treatment 25 treatment 26 of 26 of 29 skin 27 photodamaged 29 skin 28 facial 29 skin methods : eight healthy subjects underwent full - face resurfacing for photodamaged skin with two fractionated co ( 2 ) laser devices using manufacturer [-] recommended settings for facial rejuvenation . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 5 subjects 2 : 16 fractionated 2 : 31 . 3 eight 5 subjects 4 healthy 5 subjects 5 subjects 6 underwent 6 underwent 10 resurfacing 6 underwent 11 for 7 full 8 - 7 full 10 resurfacing 9 face 10 resurfacing 11 for 13 skin 12 photodamaged 13 skin 13 skin 14 with 13 skin 16 fractionated 14 with 15 two 16 fractionated 22 devices 16 fractionated 23 using 17 co 19 2 17 co 22 devices 18 ( 19 2 19 2 20 ) 21 laser 22 devices 23 using 27 settings 24 manufacturer 26 recommended 26 recommended 27 settings 27 settings 28 for 28 for 30 rejuvenation 29 facial 30 rejuvenation for each subject , one device with a rolling handpiece was used on one side and a second device with a stamping handpiece was used on the other . 0 ###LEFT-WALL### 6 device 0 ###LEFT-WALL### 12 used 0 ###LEFT-WALL### 16 and 0 ###LEFT-WALL### 29 . 1 for 3 subject 1 for 4 , 1 for 6 device 2 each 3 subject 5 one 6 device 6 device 7 with 6 device 11 was 7 with 10 handpiece 8 a 10 handpiece 9 rolling 10 handpiece 11 was 12 used 12 used 13 on 13 on 15 side 14 one 15 side 16 and 19 device 16 and 25 used 17 a 19 device 18 second 19 device 19 device 20 with 19 device 24 was 20 with 23 handpiece 21 a 23 handpiece 22 stamping 23 handpiece 24 was 25 used 25 used 26 on 26 on 28 other 27 the 28 other patients were evaluated 3 months postoperatively and photographed . 0 ###LEFT-WALL### 1 patients 0 ###LEFT-WALL### 2 were 0 ###LEFT-WALL### 9 . 1 patients 2 were 2 were 7 and 3 evaluated 5 months 3 evaluated 6 postoperatively 3 evaluated 7 and 4 3 5 months 7 and 8 photographed a blinded physician investigator assessed the photographs and rated each side for improvement in four categories ( wrinkles , pigmentation , skin laxity , and overall appearance ) . 0 ###LEFT-WALL### 4 investigator 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 29 . 1 a 4 investigator 2 blinded 3 physician 3 physician 4 investigator 4 investigator 8 and 5 assessed 7 photographs 5 assessed 8 and 6 the 7 photographs 8 and 9 rated 8 and 14 in 9 rated 11 side 10 each 11 side 11 side 12 for 12 for 13 improvement 14 in 16 categories 15 four 16 categories 16 categories 18 wrinkles 16 categories 25 and 17 ( 18 wrinkles 18 wrinkles 19 , 19 , 25 and 20 pigmentation 21 , 21 , 23 laxity 21 , 25 and 22 skin 23 laxity 24 , 25 and 25 and 27 appearance 25 and 28 ) 26 overall 27 appearance patient ratings for overall improvement for each side were also recorded . 0 ###LEFT-WALL### 2 ratings 0 ###LEFT-WALL### 11 recorded 0 ###LEFT-WALL### 12 . 1 patient 2 ratings 2 ratings 3 for 2 ratings 9 were 3 for 5 improvement 4 overall 5 improvement 5 improvement 6 for 6 for 8 side 7 each 8 side 9 were 11 recorded 10 also 11 recorded results : all patients had improved on the basis of photographic and clinical assessments at 3 months . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 18 . 2 : 4 patients 2 : 6 improved 3 all 4 patients 4 patients 5 had 5 had 6 improved 6 improved 7 on 6 improved 15 at 7 on 9 basis 8 the 9 basis 9 basis 10 of 10 of 14 assessments 11 photographic 12 and 12 and 13 clinical 12 and 14 assessments 15 at 17 months 16 3 17 months no significant differences in patient ratings of overall improvement and physician - measured parameters of clinical improvement were found , although intraoperative times and pain ratings were greater with the laser with the stamping handpiece . 0 ###LEFT-WALL### 1 no 0 ###LEFT-WALL### 12 - 0 ###LEFT-WALL### 27 were 0 ###LEFT-WALL### 36 . 1 no 10 and 2 significant 3 differences 3 differences 4 in 3 differences 10 and 4 in 6 ratings 5 patient 6 ratings 6 ratings 7 of 7 of 9 improvement 8 overall 9 improvement 10 and 11 physician 12 - 14 parameters 12 - 19 found 13 measured 14 parameters 14 parameters 15 of 14 parameters 18 were 15 of 17 improvement 16 clinical 17 improvement 18 were 19 found 19 found 21 although 20 , 21 although 21 although 22 intraoperative 22 intraoperative 27 were 23 times 24 and 24 and 26 ratings 24 and 27 were 25 pain 26 ratings 27 were 28 greater 28 greater 29 with 29 with 31 laser 30 the 31 laser 31 laser 32 with 32 with 35 handpiece 33 the 35 handpiece 34 stamping 35 handpiece no complications were experienced with either device . 0 ###LEFT-WALL### 2 complications 0 ###LEFT-WALL### 4 experienced 0 ###LEFT-WALL### 8 . 1 no 2 complications 2 complications 3 were 3 were 4 experienced 4 experienced 5 with 5 with 7 device 6 either 7 device conclusions : both fractionated co ( 2 ) resurfacing devices used in the study were safe and effective for the treatment of photodamaged facial skin , but the modality using a stamping handpiece was associated with longer operative times and greater intraoperative pain . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 44 . 2 : 4 fractionated 2 : 15 were 2 : 27 but 3 both 4 fractionated 4 fractionated 15 were 5 co 7 2 5 co 9 resurfacing 6 ( 7 2 7 2 8 ) 9 resurfacing 10 devices 10 devices 11 used 10 devices 15 were 11 used 12 in 12 in 14 study 13 the 14 study 15 were 17 and 16 safe 17 and 17 and 18 effective 18 effective 19 for 19 for 21 treatment 20 the 21 treatment 21 treatment 22 of 22 of 25 skin 23 photodamaged 25 skin 24 facial 25 skin 26 , 27 but 27 but 29 modality 27 but 35 associated 28 the 29 modality 29 modality 30 using 29 modality 34 was 30 using 33 handpiece 31 a 33 handpiece 32 stamping 33 handpiece 34 was 35 associated 35 associated 36 with 36 with 43 pain 37 longer 38 operative 38 operative 43 pain 39 times 40 and 40 and 41 greater 40 and 43 pain 42 intraoperative 43 pain the authors have indicated no significant interest with commercial supporters . 0 ###LEFT-WALL### 2 authors 0 ###LEFT-WALL### 4 indicated 0 ###LEFT-WALL### 11 . 1 the 2 authors 2 authors 3 have 3 have 4 indicated 4 indicated 7 interest 4 indicated 8 with 5 no 7 interest 6 significant 7 interest 8 with 10 supporters 9 commercial 10 supporters methods : eleven female participants with fitzpatrick skin types ii to iii and facial wrinkles underwent a single full - face fractional ablative treatment with a 2,790 [-] nm er:ysgg laser . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 5 participants 2 : 8 skin 2 : 13 and 2 : 32 . 3 eleven 5 participants 4 female 5 participants 5 participants 6 with 5 participants 8 skin 6 with 7 fitzpatrick 8 skin 9 types 8 skin 11 to 9 types 10 ii 11 to 12 iii 13 and 15 wrinkles 13 and 16 underwent 14 facial 15 wrinkles 15 wrinkles 16 underwent 16 underwent 24 treatment 16 underwent 25 with 17 a 24 treatment 18 single 21 face 19 full 20 - 19 full 21 face 21 face 24 treatment 22 fractional 24 treatment 23 ablative 24 treatment 25 with 31 laser 26 a 31 laser 27 2,790 29 nm 29 nm 31 laser 30 er:ysgg 31 laser follow - up visits were completed at 1 , 2 [,] and 6 weeks 3 and 6 months . 0 ###LEFT-WALL### 1 follow 0 ###LEFT-WALL### 2 - 2 - 4 visits 2 - 6 completed 2 - 9 , 2 - 19 . 3 up 4 visits 4 visits 5 were 5 were 6 completed 6 completed 7 at 7 at 8 1 9 , 16 and 10 2 12 and 12 and 13 6 12 and 14 weeks 14 weeks 15 3 14 weeks 16 and 16 and 18 months 17 6 18 months quartile [improvement] [scale] ( 0 - 4 ) and fitzpatrick wrinkle scores ( 1 - 9 ) were used for the assessments . 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 19 used 0 ###LEFT-WALL### 23 . 1 quartile 6 - 1 quartile 9 and 4 ( 6 - 5 0 6 - 6 - 7 4 6 - 8 ) 9 and 12 scores 9 and 15 - 9 and 18 were 10 fitzpatrick 12 scores 11 wrinkle 12 scores 13 ( 15 - 14 1 15 - 15 - 16 9 15 - 17 ) 18 were 19 used 19 used 20 for 20 for 22 assessments 21 the 22 assessments results : based on blinded photographic assessments , the mean difference in fitzpatrick wrinkle scores for full face wrinkles was 1.5 ± 1.2 ( a reduction from 6.6 to 5.1 [;] paired [t] - test , p = [.] 003 ) . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 3 based 0 ###LEFT-WALL### 8 , 0 ###LEFT-WALL### 35 test 0 ###LEFT-WALL### 42 . 1 results 2 : 2 : 3 based 3 based 4 on 4 on 7 assessments 5 blinded 7 assessments 6 photographic 7 assessments 8 , 11 difference 8 , 20 was 9 the 11 difference 10 mean 11 difference 11 difference 12 in 11 difference 16 for 11 difference 20 was 12 in 15 scores 13 fitzpatrick 14 wrinkle 14 wrinkle 15 scores 16 for 19 wrinkles 17 full 18 face 18 face 19 wrinkles 20 was 22 ± 21 1.5 22 ± 22 ± 23 1.2 22 ± 35 test 23 1.2 26 reduction 23 1.2 35 test 24 ( 26 reduction 25 a 26 reduction 26 reduction 27 from 26 reduction 34 - 27 from 29 to 28 6.6 29 to 29 to 30 5.1 29 to 32 paired 35 test 38 = 36 , 38 = 37 p 38 = 38 = 40 003 38 = 41 ) there was also a statistically significant mean reduction of 1.7 ± 1.3 in perioral wrinkle scores ( from 6.7 to 5.0 [;] p = [.] 002 ) . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 was 0 ###LEFT-WALL### 28 . 1 there 2 was 2 was 3 also 2 was 8 reduction 4 a 8 reduction 5 statistically 6 significant 6 significant 8 reduction 7 mean 8 reduction 8 reduction 9 of 8 reduction 20 to 9 of 16 scores 10 1.7 16 scores 11 ± 16 scores 12 1.3 13 in 13 in 16 scores 14 perioral 15 wrinkle 15 wrinkle 16 scores 17 ( 20 to 18 from 20 to 19 6.7 20 to 20 to 21 5.0 20 to 24 = 20 to 27 ) 23 p 24 = 24 = 26 002 no serious adverse events were reported . 0 ###LEFT-WALL### 4 events 0 ###LEFT-WALL### 6 reported 0 ###LEFT-WALL### 7 . 1 no 4 events 2 serious 4 events 3 adverse 4 events 4 events 5 were 5 were 6 reported conclusion : a novel , fractionated [,] ablative 2,790 [-] nm er:ysgg laser can safely [and] effectively treat [photodamage] and [perioral] wrinkles in a single treatment using a high - fluence , high - density protocol . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 37 . 2 : 13 laser 3 a 13 laser 4 novel 5 , 4 novel 13 laser 6 fractionated 13 laser 8 ablative 13 laser 9 2,790 11 nm 11 nm 13 laser 12 er:ysgg 13 laser 13 laser 20 and 14 can 18 treat 14 can 20 and 15 safely 18 treat 17 effectively 18 treat 20 and 22 wrinkles 20 and 23 in 20 and 26 treatment 20 and 27 using 24 a 25 single 24 a 26 treatment 25 single 26 treatment 27 using 36 protocol 28 a 29 high 28 a 36 protocol 29 high 31 fluence 29 high 35 density 30 - 31 fluence 31 fluence 32 , 33 high 34 - 33 high 35 density 35 density 36 protocol cutera provided the equipment used in this study and funding to dr [.] goldberg . 0 ###LEFT-WALL### 1 cutera 0 ###LEFT-WALL### 2 provided 0 ###LEFT-WALL### 15 . 1 cutera 2 provided 2 provided 4 equipment 3 the 4 equipment 4 equipment 5 used 5 used 6 in 5 used 11 to 6 in 9 and 7 this 8 study 8 study 9 and 9 and 10 funding 11 to 14 goldberg 12 dr 14 goldberg background : this pilot study compared a monophasic hyaluronic acid dermal filler with a biphasic filler for the correction of nasolabial folds . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 23 . 2 : 5 study 2 : 6 compared 3 this 5 study 4 pilot 5 study 5 study 6 compared 6 compared 12 filler 6 compared 13 with 7 a 12 filler 8 monophasic 12 filler 9 hyaluronic 12 filler 10 acid 12 filler 11 dermal 12 filler 13 with 16 filler 14 a 15 biphasic 14 a 16 filler 15 biphasic 16 filler 16 filler 17 for 16 filler 20 of 17 for 19 correction 18 the 19 correction 20 of 22 folds 21 nasolabial 22 folds methods : participant - and assessor - blinded , randomized clinical trial involving participants with moderate [to] severe nasolabial folds . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 21 . 2 : 5 and 2 : 10 randomized 3 participant 5 and 4 - 5 and 5 and 6 assessor 5 and 8 blinded 5 and 10 randomized 7 - 8 blinded 8 blinded 9 , 10 randomized 14 participants 10 randomized 15 with 11 clinical 12 trial 12 trial 14 participants 13 involving 14 participants 15 with 20 folds 16 moderate 20 folds 18 severe 20 folds 19 nasolabial 20 folds split - face design comparing a monophase hyaluronic acid ( ha ) filler ( mono - ha ) with a biphasic ha filler ( bi - ha ) . 0 ###LEFT-WALL### 3 face 0 ###LEFT-WALL### 29 . 1 split 2 - 1 split 3 face 3 face 4 design 3 face 19 with 4 design 5 comparing 5 comparing 13 filler 6 a 13 filler 7 monophase 13 filler 8 hyaluronic 13 filler 9 acid 11 ha 9 acid 12 ) 9 acid 13 filler 10 ( 11 ha 11 ha 12 ) 13 filler 17 ha 14 ( 17 ha 15 mono 16 - 15 mono 17 ha 17 ha 18 ) 19 with 23 filler 20 a 23 filler 21 biphasic 23 filler 22 ha 23 filler 23 filler 25 bi 24 ( 25 bi 25 bi 27 ha 25 bi 28 ) 26 - 27 ha 27 ha 28 ) injection [with] touch - up after 1 month . 0 ###LEFT-WALL### 3 touch 1 injection 3 touch 3 touch 5 up 4 - 5 up 5 up 6 after 5 up 9 . 6 after 8 month 7 1 8 month wrinkle improvement was measured before and after injection [and] after 1 , 2 , 4 , and 7 months , using the wrinkle severity rating scale and the global aesthetic improvement scale as outcome criteria . 0 ###LEFT-WALL### 2 improvement 0 ###LEFT-WALL### 4 measured 0 ###LEFT-WALL### 36 . 1 wrinkle 2 improvement 2 improvement 3 was 3 was 4 measured 4 measured 6 and 4 measured 33 as 5 before 6 and 6 and 7 after 7 after 17 and 8 injection 10 after 8 injection 17 and 10 after 11 1 11 1 13 2 11 1 15 4 12 , 13 2 13 2 14 , 14 , 15 4 15 4 16 , 17 and 19 months 17 and 20 , 17 and 21 using 18 7 19 months 21 using 27 and 22 the 27 and 23 wrinkle 24 severity 24 severity 25 rating 25 rating 26 scale 26 scale 27 and 27 and 32 scale 28 the 32 scale 29 global 30 aesthetic 30 aesthetic 31 improvement 31 improvement 32 scale 33 as 35 criteria 34 outcome 35 criteria an optional treatment was offered at the end of the study , with participants allowed to choose one of the products . 0 ###LEFT-WALL### 3 treatment 0 ###LEFT-WALL### 5 offered 1 an 2 optional 1 an 3 treatment 2 optional 3 treatment 3 treatment 4 was 4 was 5 offered 5 offered 6 at 6 at 8 end 7 the 8 end 8 end 9 of 9 of 11 study 10 the 11 study 11 study 13 with 12 , 13 with 13 with 14 participants 13 with 22 . 14 participants 15 allowed 15 allowed 16 to 15 allowed 17 choose 16 to 17 choose 17 choose 18 one 18 one 19 of 19 of 21 products 20 the 21 products objective : evaluation of efficacy and safety of both products . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 11 . 1 objective 2 : 2 : 3 evaluation 3 evaluation 4 of 3 evaluation 8 of 4 of 6 and 5 efficacy 6 and 6 and 7 safety 8 of 10 products 9 both 10 products results : both products showed immediate , good results after injection and touch - up and demonstrated good durability over time . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 4 products 2 : 16 and 2 : 22 . 3 both 4 products 4 products 16 and 5 showed 9 results 5 showed 10 after 5 showed 15 up 5 showed 16 and 6 immediate 7 , 6 immediate 9 results 8 good 9 results 10 after 12 and 11 injection 12 and 12 and 13 touch 12 and 14 - 16 and 17 demonstrated 16 and 20 over 17 demonstrated 19 durability 18 good 19 durability 20 over 21 time participant preference for optional treatment at the end of the study favoured mono - ha . 0 ###LEFT-WALL### 2 preference 0 ###LEFT-WALL### 12 favoured 0 ###LEFT-WALL### 16 . 1 participant 2 preference 2 preference 3 for 2 preference 12 favoured 3 for 5 treatment 4 optional 5 treatment 5 treatment 6 at 6 at 8 end 7 the 8 end 8 end 9 of 9 of 11 study 10 the 11 study 12 favoured 15 ha 13 mono 14 - 13 mono 15 ha both products were well tolerated , without serious adverse events . 0 ###LEFT-WALL### 2 products 0 ###LEFT-WALL### 3 were 1 both 2 products 2 products 3 were 3 were 4 well 4 well 5 tolerated 5 tolerated 7 without 6 , 7 without 7 without 10 events 7 without 11 . 8 serious 10 events 9 adverse 10 events conclusion : the effect after injection of mono - ha and bi - ha is generally comparable , although there was a trend in favor of mono - ha . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 1 conclusion 2 : 2 : 4 effect 2 : 5 after 3 the 4 effect 5 after 6 injection 5 after 15 is 6 injection 7 of 6 injection 15 is 7 of 14 ha 8 mono 11 and 8 mono 14 ha 9 - 11 and 10 ha 11 and 11 and 12 bi 11 and 13 - 15 is 16 generally 15 is 17 comparable 17 comparable 19 although 18 , 19 although 19 although 20 there 19 although 21 was 19 although 30 . 20 there 21 was 21 was 23 trend 21 was 24 in 22 a 23 trend 24 in 25 favor 25 favor 26 of 26 of 29 ha 27 mono 28 - 27 mono 29 ha materials and funding for this study were provided by teoxane , geneva , switzerland . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 8 provided 0 ###LEFT-WALL### 13 , 0 ###LEFT-WALL### 15 . 1 materials 2 and 2 and 3 funding 2 and 4 for 2 and 7 were 4 for 6 study 5 this 6 study 7 were 8 provided 8 provided 9 by 9 by 10 teoxane 10 teoxane 12 geneva 11 , 12 geneva 12 geneva 13 , 13 , 14 switzerland the focus of the present article was to analyze processes that determine the enactment and age effect in a multi - trial free recall paradigm by looking at the serial position effects . 0 ###LEFT-WALL### 2 focus 0 ###LEFT-WALL### 33 . 1 the 2 focus 2 focus 3 of 2 focus 7 was 3 of 6 article 4 the 6 article 5 present 6 article 7 was 8 to 7 was 15 and 8 to 15 and 9 analyze 10 processes 9 analyze 15 and 10 processes 11 that 10 processes 12 determine 11 that 12 determine 12 determine 14 enactment 13 the 14 enactment 15 and 16 age 15 and 18 in 15 and 26 by 15 and 32 effects 16 age 17 effect 18 in 25 paradigm 19 a 20 multi 19 a 25 paradigm 20 multi 21 - 20 multi 22 trial 22 trial 25 paradigm 23 free 24 recall 24 recall 25 paradigm 26 by 27 looking 27 looking 28 at 28 at 30 serial 29 the 30 serial 31 position 32 effects in an experimental study ( [see] schatz et al [2010] ) , the performance - enhancing effect of enactive encoding and repeated learning was tested with older and younger participants . 0 ###LEFT-WALL### 16 enhancing 0 ###LEFT-WALL### 25 tested 0 ###LEFT-WALL### 31 . 1 in 4 study 1 in 16 enhancing 2 an 3 experimental 2 an 4 study 3 experimental 4 study 4 study 9 al 4 study 14 performance 5 ( 9 al 7 schatz 9 al 8 et 9 al 9 al 11 ) 12 , 14 performance 13 the 14 performance 14 performance 15 - 16 enhancing 17 effect 16 enhancing 24 was 17 effect 18 of 18 of 21 and 19 enactive 20 encoding 20 encoding 21 and 21 and 23 learning 22 repeated 23 learning 24 was 25 tested 25 tested 26 with 26 with 30 participants 27 older 28 and 28 and 29 younger 28 and 30 participants as expected , there was a steady improvement of memory performance as a function of repeated learning regardless of age . 0 ###LEFT-WALL### 4 there 0 ###LEFT-WALL### 5 was 0 ###LEFT-WALL### 21 . 1 as 2 expected 1 as 3 , 1 as 4 there 2 expected 3 , 4 there 5 was 5 was 8 improvement 5 was 12 as 5 was 19 of 6 a 7 steady 6 a 8 improvement 7 steady 8 improvement 8 improvement 9 of 9 of 11 performance 10 memory 11 performance 12 as 14 function 13 a 14 function 14 function 15 of 15 of 17 learning 16 repeated 17 learning 18 regardless 19 of 19 of 20 age in addition , enactive encoding led to a better memory performance than verbal encoding in both age groups . 0 ###LEFT-WALL### 5 encoding 0 ###LEFT-WALL### 6 led 0 ###LEFT-WALL### 19 . 1 in 2 addition 1 in 3 , 1 in 5 encoding 4 enactive 5 encoding 5 encoding 6 led 6 led 7 to 6 led 12 than 6 led 15 in 7 to 11 performance 8 a 11 performance 9 better 10 memory 10 memory 11 performance 12 than 14 encoding 13 verbal 14 encoding 15 in 18 groups 16 both 18 groups 17 age 18 groups furthermore , younger adults outperformed the elderly regardless of type [of] encoding . 0 ###LEFT-WALL### 4 adults 0 ###LEFT-WALL### 5 outperformed 0 ###LEFT-WALL### 13 . 1 furthermore 2 , 1 furthermore 4 adults 3 younger 4 adults 4 adults 5 outperformed 5 outperformed 7 elderly 5 outperformed 9 of 6 the 7 elderly 8 regardless 9 of 9 of 12 encoding 10 type 12 encoding analyses in the present article show that encoding by enacting seems to profit especially from remembering the last items of a presented list . 0 ###LEFT-WALL### 1 analyses 0 ###LEFT-WALL### 6 show 0 ###LEFT-WALL### 24 . 1 analyses 2 in 1 analyses 6 show 2 in 5 article 3 the 5 article 4 present 5 article 6 show 8 encoding 6 show 11 seems 7 that 8 encoding 8 encoding 9 by 8 encoding 11 seems 9 by 10 enacting 11 seems 12 to 11 seems 13 profit 12 to 13 profit 13 profit 14 especially 14 especially 15 from 15 from 16 remembering 16 remembering 19 items 17 the 18 last 17 the 19 items 19 items 20 of 20 of 23 list 21 a 23 list 22 presented 23 list [regarding] age differences , younger outperformed older participants in nearly all item positions . 0 ###LEFT-WALL### 2 age 2 age 3 differences 3 differences 8 participants 4 , 8 participants 5 younger 8 participants 6 outperformed 8 participants 7 older 8 participants 8 participants 9 in 8 participants 14 . 9 in 13 positions 10 nearly 11 all 11 all 13 positions 12 item 13 positions the performance enhancement after task repetition is due to a higher amount of recalled items in the middle positions in a subject performed task ( spt ) and a verbal task ( vt ) as well as the last positions of a learned list in vt . 0 ###LEFT-WALL### 3 enhancement 0 ###LEFT-WALL### 7 is 0 ###LEFT-WALL### 47 . 1 the 3 enhancement 2 performance 3 enhancement 3 enhancement 4 after 3 enhancement 7 is 4 after 6 repetition 5 task 6 repetition 7 is 9 to 7 is 16 in 7 is 37 as 8 due 9 to 9 to 12 amount 10 a 12 amount 11 higher 12 amount 12 amount 13 of 13 of 15 items 14 recalled 15 items 16 in 28 and 17 the 19 positions 18 middle 19 positions 19 positions 20 in 19 positions 28 and 20 in 24 task 21 a 24 task 22 subject 23 performed 23 performed 24 task 24 task 26 spt 25 ( 26 spt 26 spt 27 ) 28 and 31 task 28 and 33 vt 29 a 30 verbal 29 a 31 task 30 verbal 31 task 32 ( 33 vt 33 vt 34 ) 35 as 36 well 36 well 37 as 37 as 40 positions 38 the 39 last 38 the 40 positions 40 positions 41 of 40 positions 45 in 41 of 44 list 42 a 44 list 43 learned 44 list 45 in 46 vt for volume restoration of the face , hyaluronic acid is conventionally injected through long , large - bore , 18 - gauge needles because of the higher viscosity [subtypes] required . 0 ###LEFT-WALL### 9 acid 0 ###LEFT-WALL### 12 injected 0 ###LEFT-WALL### 15 , 0 ###LEFT-WALL### 31 . 1 for 3 restoration 1 for 7 , 1 for 9 acid 2 volume 3 restoration 3 restoration 4 of 4 of 6 face 5 the 6 face 8 hyaluronic 9 acid 9 acid 10 is 10 is 12 injected 11 conventionally 12 injected 12 injected 13 through 13 through 14 long 15 , 18 bore 15 , 19 , 16 large 17 - 16 large 18 bore 19 , 20 18 19 , 21 - 20 18 21 - 21 - 22 gauge 22 gauge 23 needles 22 gauge 24 because 24 because 25 of 25 of 28 viscosity 26 the 28 viscosity 27 higher 28 viscosity 28 viscosity 30 required these hyaluronic acids are either more highly cross - linked [or] [larger] in particle size than [the] less - [viscous] [subtypes] . 0 ###LEFT-WALL### 3 acids 0 ###LEFT-WALL### 8 cross 0 ###LEFT-WALL### 22 . 1 these 3 acids 2 hyaluronic 3 acids 3 acids 4 are 4 are 8 cross 5 either 8 cross 6 more 7 highly 7 highly 8 cross 8 cross 10 linked 9 - 10 linked 10 linked 13 in 10 linked 16 than 10 linked 19 - 13 in 15 size 14 particle 15 size 16 than 18 less the microdepot injection technique involves using the 31 [-] gauge bd insulin syringe ( becton - dickinson , north ryde , nsw australia ) to deposit small amounts of filler ( 0.05 - 0.1 ml ) throughout the area of volume loss . 0 ###LEFT-WALL### 4 technique 0 ###LEFT-WALL### 5 involves 0 ###LEFT-WALL### 43 . 1 the 4 technique 2 microdepot 3 injection 3 injection 4 technique 4 technique 5 involves 5 involves 6 using 6 using 13 syringe 6 using 25 to 7 the 13 syringe 8 31 10 gauge 10 gauge 13 syringe 11 bd 13 syringe 12 insulin 13 syringe 13 syringe 15 becton 13 syringe 17 dickinson 13 syringe 23 australia 14 ( 15 becton 15 becton 16 - 16 - 17 dickinson 17 dickinson 18 , 18 , 23 australia 19 north 20 ryde 20 ryde 22 nsw 21 , 22 nsw 22 nsw 23 australia 23 australia 24 ) 25 to 26 deposit 26 deposit 28 amounts 26 deposit 33 - 26 deposit 37 throughout 27 small 28 amounts 28 amounts 29 of 29 of 30 filler 31 ( 33 - 32 0.05 33 - 33 - 35 ml 33 - 36 ) 34 0.1 35 ml 37 throughout 39 area 38 the 39 area 39 area 40 of 40 of 42 loss 41 volume 42 loss the procedure is extremely well tolerated , requiring only topical and ice anaesthesia . 0 ###LEFT-WALL### 2 procedure 0 ###LEFT-WALL### 6 tolerated 1 the 2 procedure 2 procedure 3 is 3 is 5 well 3 is 6 tolerated 4 extremely 5 well 6 tolerated 8 requiring 7 , 8 requiring 8 requiring 9 only 8 requiring 11 and 8 requiring 14 . 10 topical 11 and 11 and 13 anaesthesia 12 ice 13 anaesthesia using this method , volume restoration can be achieved naturally [and] progressively over a period of time . 0 ###LEFT-WALL### 6 restoration 0 ###LEFT-WALL### 9 achieved 0 ###LEFT-WALL### 18 . 1 using 3 method 1 using 4 , 1 using 6 restoration 2 this 3 method 5 volume 6 restoration 6 restoration 7 can 7 can 8 be 8 be 9 achieved 9 achieved 10 naturally 9 achieved 12 progressively 9 achieved 13 over 13 over 15 period 14 a 15 period 15 period 16 of 16 of 17 time fractional filling every 3 - 4 months is continued until the desired level of volume correction is attained . 0 ###LEFT-WALL### 1 fractional 0 ###LEFT-WALL### 9 continued 0 ###LEFT-WALL### 19 . 1 fractional 2 filling 1 fractional 8 is 1 fractional 9 continued 2 filling 3 every 2 filling 8 is 3 every 7 months 4 3 5 - 5 - 6 4 5 - 7 months 9 continued 10 until 10 until 13 level 10 until 18 attained 11 the 13 level 12 desired 13 level 13 level 14 of 13 level 17 is 14 of 16 correction 15 volume 16 correction 17 is 18 attained patients undergoing fractional filling followed over [a] 12 - month period did not indicate any observable compromise in filler longevity , even when highly viscous hyaluronic acid fillers were injected through small - bore [,] 31 - gauge insulin syringes . 0 ###LEFT-WALL### 11 period 0 ###LEFT-WALL### 14 indicate 0 ###LEFT-WALL### 21 , 0 ###LEFT-WALL### 37 - 0 ###LEFT-WALL### 41 . 1 patients 11 period 2 undergoing 4 filling 2 undergoing 9 - 2 undergoing 11 period 3 fractional 4 filling 4 filling 5 followed 5 followed 6 over 6 over 8 12 10 month 11 period 11 period 12 did 12 did 13 not 12 did 14 indicate 14 indicate 17 compromise 15 any 17 compromise 16 observable 17 compromise 17 compromise 18 in 18 in 20 longevity 19 filler 20 longevity 21 , 22 even 22 even 23 when 22 even 31 through 23 when 28 fillers 23 when 30 injected 24 highly 25 viscous 25 viscous 27 acid 26 hyaluronic 27 acid 27 acid 28 fillers 28 fillers 29 were 29 were 30 injected 31 through 34 bore 32 small 33 - 32 small 34 bore 34 bore 36 31 36 31 37 - 37 - 40 syringes 38 gauge 40 syringes 39 insulin 40 syringes epidemiological studies suggest a protective role of omega - 3 [poly] - unsaturated fatty acids ( n - 3 pufa ) against alzheimer 's disease ( ad ) . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 3 suggest 0 ###LEFT-WALL### 29 . 1 epidemiological 2 studies 2 studies 3 suggest 3 suggest 6 role 3 suggest 22 against 4 a 5 protective 4 a 6 role 5 protective 6 role 6 role 7 of 6 role 15 acids 7 of 8 omega 8 omega 10 3 9 - 10 3 10 3 12 - 12 - 15 acids 13 unsaturated 15 acids 14 fatty 15 acids 15 acids 20 pufa 15 acids 21 ) 16 ( 20 pufa 17 n 18 - 18 - 19 3 18 - 20 pufa 20 pufa 21 ) 22 against 25 disease 23 alzheimer 24 's 24 's 25 disease 25 disease 27 ad 26 ( 27 ad 27 ad 28 ) however , most intervention studies of supplementation with n - 3 pufa have yielded disappointing results . 0 ###LEFT-WALL### 5 studies 0 ###LEFT-WALL### 14 yielded 0 ###LEFT-WALL### 17 . 1 however 2 , 1 however 5 studies 3 most 5 studies 4 intervention 5 studies 5 studies 6 of 5 studies 13 have 6 of 7 supplementation 7 supplementation 8 with 8 with 12 pufa 9 n 10 - 10 - 11 3 10 - 12 pufa 13 have 14 yielded 14 yielded 16 results 15 disappointing 16 results one reason for such discordant results may result from inadequate targeting of individuals who might benefit from the supplementation [,] in particular because of their genetic susceptibility to ad . 0 ###LEFT-WALL### 2 reason 0 ###LEFT-WALL### 8 result 0 ###LEFT-WALL### 30 . 1 one 2 reason 2 reason 3 for 2 reason 7 may 3 for 6 results 4 such 6 results 5 discordant 6 results 7 may 8 result 8 result 9 from 8 result 22 particular 8 result 23 because 8 result 28 to 9 from 11 targeting 10 inadequate 11 targeting 11 targeting 12 of 12 of 13 individuals 13 individuals 14 who 13 individuals 15 might 14 who 15 might 15 might 16 benefit 16 benefit 17 from 17 from 19 supplementation 18 the 19 supplementation 21 in 22 particular 23 because 24 of 24 of 27 susceptibility 25 their 27 susceptibility 26 genetic 27 susceptibility 28 to 29 ad the ε4 allele of the apolipoprotein e gene ( apoe ) is a genetic risk factor for late - onset ad . 0 ###LEFT-WALL### 3 allele 0 ###LEFT-WALL### 12 is 0 ###LEFT-WALL### 22 . 1 the 3 allele 2 ε4 3 allele 3 allele 4 of 3 allele 12 is 4 of 8 gene 5 the 8 gene 6 apolipoprotein 7 e 6 apolipoprotein 8 gene 8 gene 10 apoe 9 ( 10 apoe 10 apoe 11 ) 12 is 16 factor 13 a 14 genetic 13 a 16 factor 14 genetic 16 factor 15 risk 16 factor 16 factor 17 for 17 for 21 ad 18 late 19 - 18 late 20 onset 20 onset 21 ad apoe plays a key role in the transport of cholesterol and other lipids involved in brain composition and functioning . 0 ###LEFT-WALL### 1 apoe 0 ###LEFT-WALL### 2 plays 0 ###LEFT-WALL### 20 . 1 apoe 2 plays 2 plays 5 role 2 plays 6 in 2 plays 15 in 3 a 5 role 4 key 5 role 6 in 8 transport 7 the 8 transport 8 transport 9 of 8 transport 14 involved 9 of 11 and 10 cholesterol 11 and 11 and 13 lipids 12 other 13 lipids 15 in 18 and 16 brain 17 composition 17 composition 18 and 18 and 19 functioning the action of n - 3 pufa on the aging brain might therefore differ according to apoe [polymorphism] . 0 ###LEFT-WALL### 2 action 0 ###LEFT-WALL### 14 differ 0 ###LEFT-WALL### 19 . 1 the 2 action 2 action 3 of 2 action 12 might 3 of 7 pufa 4 n 5 - 5 - 6 3 5 - 7 pufa 7 pufa 8 on 8 on 11 brain 9 the 11 brain 10 aging 11 brain 12 might 14 differ 13 therefore 14 differ 14 differ 16 to 15 according 16 to 16 to 17 apoe the aim of this review is to examine the interaction between dietary fatty acids and apoe [genotype] on the risk for ad . 0 ###LEFT-WALL### 2 aim 0 ###LEFT-WALL### 23 . 1 the 2 aim 2 aim 3 of 2 aim 6 is 3 of 5 review 4 this 5 review 6 is 7 to 6 is 8 examine 7 to 8 examine 8 examine 10 interaction 8 examine 11 between 8 examine 18 on 9 the 10 interaction 11 between 15 and 12 dietary 14 acids 13 fatty 14 acids 14 acids 15 and 15 and 16 apoe 18 on 20 risk 19 the 20 risk 20 risk 21 for 21 for 22 ad carriers of the ε4 allele tend to be the most responsive to changes in dietary fat and cholesterol . 0 ###LEFT-WALL### 1 carriers 0 ###LEFT-WALL### 6 tend 0 ###LEFT-WALL### 19 . 1 carriers 2 of 1 carriers 6 tend 2 of 5 allele 3 the 5 allele 4 ε4 5 allele 6 tend 7 to 6 tend 8 be 7 to 8 be 8 be 17 and 9 the 17 and 10 most 11 responsive 10 most 17 and 11 responsive 12 to 12 to 13 changes 13 changes 14 in 14 in 16 fat 15 dietary 16 fat 17 and 18 cholesterol conversely , several epidemiological studies suggest a protective effect of long - chain n - 3 pufa on [cognitive] decline only in those who do not carry ε4 but with inconsistent results . 0 ###LEFT-WALL### 3 several 0 ###LEFT-WALL### 20 decline 0 ###LEFT-WALL### 33 . 1 conversely 2 , 1 conversely 3 several 3 several 5 studies 3 several 18 on 3 several 20 decline 4 epidemiological 5 studies 5 studies 6 suggest 6 suggest 9 effect 6 suggest 18 on 7 a 9 effect 8 protective 9 effect 9 effect 10 of 10 of 17 pufa 11 long 12 - 11 long 17 pufa 13 chain 17 pufa 14 n 15 - 15 - 16 3 15 - 17 pufa 20 decline 21 only 21 only 22 in 22 in 23 those 23 those 24 who 23 those 25 do 23 those 29 but 24 who 25 do 25 do 26 not 25 do 27 carry 27 carry 28 ε4 29 but 30 with 30 with 32 results 31 inconsistent 32 results an intervention study showed that only [non] - carriers had increased concentrations of long - chain n - 3 pufa in response to supplementation . 0 ###LEFT-WALL### 3 study 0 ###LEFT-WALL### 4 showed 0 ###LEFT-WALL### 8 - 1 an 2 intervention 1 an 3 study 2 intervention 3 study 3 study 4 showed 4 showed 5 that 4 showed 6 only 8 - 9 carriers 8 - 11 increased 8 - 25 . 9 carriers 10 had 10 had 11 increased 11 increased 12 concentrations 11 increased 23 to 12 concentrations 13 of 13 of 20 pufa 14 long 15 - 14 long 16 chain 16 chain 20 pufa 17 n 18 - 18 - 19 3 18 - 20 pufa 21 in 22 response 22 response 23 to 23 to 24 supplementation the mechanisms underlying this gene - by [-] diet interaction on ad risk may involve impaired fatty acids and cholesterol transport , altered metabolism of n - 3 pufa , glucose or ketones , or modification of other risk factors of ad in ε4 carriers . 0 ###LEFT-WALL### 35 or 0 ###LEFT-WALL### 46 . 1 the 2 mechanisms 2 mechanisms 3 underlying 2 mechanisms 35 or 3 underlying 5 gene 3 underlying 7 by 4 this 5 gene 6 - 7 by 7 by 19 and 7 by 34 , 9 diet 10 interaction 10 interaction 11 on 10 interaction 19 and 11 on 12 ad 12 ad 13 risk 12 ad 15 involve 13 risk 14 may 14 may 15 involve 15 involve 18 acids 16 impaired 18 acids 17 fatty 18 acids 19 and 21 transport 19 and 32 or 20 cholesterol 21 transport 22 , 32 or 23 altered 24 metabolism 24 metabolism 25 of 24 metabolism 30 , 25 of 29 pufa 26 n 27 - 27 - 28 3 27 - 29 pufa 30 , 31 glucose 30 , 32 or 32 or 33 ketones 32 or 34 , 35 or 36 modification 36 modification 37 of 36 modification 41 of 37 of 40 factors 38 other 40 factors 39 risk 40 factors 41 of 42 ad 42 ad 43 in 43 in 45 carriers 44 ε4 45 carriers further research is needed to explain the differential effect of n - 3 pufa on ad according to apoe [genotype] . 0 ###LEFT-WALL### 2 research 0 ###LEFT-WALL### 4 needed 0 ###LEFT-WALL### 21 . 1 further 2 research 2 research 3 is 3 is 4 needed 4 needed 5 to 4 needed 18 to 5 to 6 explain 6 explain 9 effect 6 explain 15 on 7 the 9 effect 8 differential 9 effect 9 effect 10 of 10 of 14 pufa 11 n 12 - 12 - 13 3 12 - 14 pufa 15 on 16 ad 17 according 18 to 18 to 19 apoe much of the attention [on] diet and alzheimer 's disease ( ad ) or cognition among the elderly has focused on the role of single nutrients or foods , while available information on dietary [pattern] ( dp ) analysis , which better reflects the complexity of the diet , is sparse . 0 ###LEFT-WALL### 1 much 0 ###LEFT-WALL### 20 focused 1 much 2 of 1 much 19 has 2 of 14 or 3 the 6 diet 4 attention 6 diet 6 diet 7 and 7 and 10 disease 7 and 12 ad 7 and 14 or 8 alzheimer 9 's 9 's 10 disease 11 ( 12 ad 12 ad 13 ) 14 or 15 cognition 14 or 16 among 16 among 18 elderly 17 the 18 elderly 19 has 20 focused 20 focused 21 on 20 focused 30 while 21 on 27 or 22 the 23 role 23 role 24 of 23 role 27 or 24 of 26 nutrients 25 single 26 nutrients 27 or 28 foods 29 , 30 while 30 while 32 information 30 while 50 is 30 while 52 . 31 available 32 information 32 information 33 on 32 information 50 is 33 on 39 analysis 34 dietary 37 dp 34 dietary 39 analysis 36 ( 37 dp 37 dp 38 ) 39 analysis 41 which 40 , 41 which 41 which 43 reflects 41 which 49 , 42 better 43 reflects 43 reflects 45 complexity 44 the 45 complexity 45 complexity 46 of 46 of 48 diet 47 the 48 diet 50 is 51 sparse in this review , we describe different patterning approaches and present studies performed to date that have assessed the associations between dps and risk of ad or cognitive function in the elderly . 0 ###LEFT-WALL### 5 we 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 33 . 1 in 3 review 1 in 4 , 1 in 5 we 2 this 3 review 5 we 10 and 6 describe 9 approaches 6 describe 10 and 7 different 9 approaches 8 patterning 9 approaches 10 and 11 present 10 and 30 in 11 present 12 studies 12 studies 13 performed 12 studies 16 that 12 studies 17 have 13 performed 15 date 14 to 15 date 16 that 17 have 17 have 18 assessed 18 assessed 20 associations 18 assessed 21 between 19 the 20 associations 21 between 27 or 22 dps 23 and 23 and 24 risk 23 and 25 of 23 and 27 or 25 of 26 ad 27 or 29 function 28 cognitive 29 function 30 in 32 elderly 31 the 32 elderly despite differences existing among the approaches , dps characterized by higher intake of fruits , vegetables , fish , nuts and legumes , and lower intake of meats , high fat dairy , and sweets seemed to be associated with lower odds of cognitive deficits or reduced risk of ad . 0 ###LEFT-WALL### 18 fish 0 ###LEFT-WALL### 19 , 0 ###LEFT-WALL### 51 . 1 despite 2 differences 1 despite 18 fish 2 differences 3 existing 2 differences 8 dps 2 differences 16 vegetables 3 existing 4 among 4 among 6 approaches 5 the 6 approaches 7 , 8 dps 8 dps 9 characterized 8 dps 10 by 8 dps 15 , 10 by 12 intake 11 higher 12 intake 12 intake 13 of 13 of 14 fruits 15 , 16 vegetables 16 vegetables 17 , 19 , 26 intake 19 , 46 or 20 nuts 21 and 21 and 22 legumes 21 and 23 , 21 and 24 and 24 and 25 lower 24 and 26 intake 26 intake 27 of 26 intake 46 or 27 of 34 and 28 meats 29 , 29 , 32 dairy 29 , 34 and 30 high 31 fat 31 fat 32 dairy 33 , 34 and 34 and 35 sweets 36 seemed 37 to 36 seemed 39 associated 36 seemed 46 or 37 to 38 be 38 be 39 associated 39 associated 40 with 40 with 42 odds 41 lower 42 odds 42 odds 43 of 43 of 45 deficits 44 cognitive 45 deficits 46 or 47 reduced 47 reduced 48 risk 48 risk 49 of 49 of 50 ad overall , the inherent advantages as well as the existing evidence of dp analyses strongly suggest that this approach may be valuable in ad and aging research . 0 ###LEFT-WALL### 5 advantages 0 ###LEFT-WALL### 16 suggest 0 ###LEFT-WALL### 28 . 1 overall 2 , 1 overall 5 advantages 3 the 5 advantages 4 inherent 5 advantages 5 advantages 6 as 5 advantages 8 as 5 advantages 16 suggest 6 as 7 well 8 as 11 evidence 9 the 11 evidence 10 existing 11 evidence 11 evidence 12 of 12 of 14 analyses 13 dp 14 analyses 15 strongly 16 suggest 16 suggest 17 that 17 that 19 approach 17 that 21 be 18 this 19 approach 19 approach 20 may 20 may 21 be 21 be 22 valuable 22 valuable 23 in 23 in 25 and 24 ad 25 and 25 and 27 research 26 aging 27 research further studies are warranted , though , to confirm the findings in different population settings , to address some methodological issues , and possibly utilize the information for future clinical trial design . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 23 and 0 ###LEFT-WALL### 33 . 1 further 2 studies 2 studies 3 are 3 are 4 warranted 4 warranted 8 to 5 , 6 though 6 though 7 , 6 though 8 to 8 to 23 and 9 confirm 11 findings 9 confirm 23 and 10 the 11 findings 11 findings 12 in 11 findings 17 to 12 in 15 settings 13 different 14 population 14 population 15 settings 16 , 17 to 17 to 18 address 17 to 22 , 18 address 21 issues 19 some 21 issues 20 methodological 21 issues 22 , 23 and 23 and 25 utilize 24 possibly 25 utilize 25 utilize 27 information 25 utilize 28 for 26 the 27 information 28 for 32 design 29 future 31 trial 30 clinical 31 trial 31 trial 32 design there is a critical need to potentially individualize new strategies able to prevent [and] to slow down the progression of predementia and dementia syndromes . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 25 . 1 there 2 is 2 is 5 need 2 is 11 able 3 a 4 critical 3 a 5 need 4 critical 5 need 5 need 6 to 5 need 8 individualize 6 to 8 individualize 7 potentially 8 individualize 8 individualize 10 strategies 9 new 10 strategies 11 able 12 to 11 able 13 prevent 12 to 13 prevent 13 prevent 15 to 13 prevent 17 down 13 prevent 19 progression 15 to 16 slow 18 the 19 progression 19 progression 20 of 20 of 24 syndromes 21 predementia 22 and 22 and 23 dementia 22 and 24 syndromes only recently higher adherence to a mediterranean [-] type diet was associated with decreased cognitive decline although the mediterranean diet ( medi ) combines several foods , micro - and macronutrients already separately proposed as potential protective factors against dementia and predementia syndromes . 0 ###LEFT-WALL### 4 adherence 0 ###LEFT-WALL### 12 associated 1 only 3 higher 2 recently 3 higher 3 higher 4 adherence 4 adherence 5 to 4 adherence 11 was 5 to 10 diet 6 a 10 diet 7 mediterranean 9 type 9 type 10 diet 11 was 12 associated 12 associated 13 with 12 associated 17 although 13 with 16 decline 14 decreased 16 decline 15 cognitive 16 decline 17 although 20 diet 17 although 24 combines 18 the 20 diet 19 mediterranean 20 diet 20 diet 22 medi 20 diet 24 combines 21 ( 22 medi 22 medi 23 ) 24 combines 30 and 24 combines 35 as 25 several 26 foods 26 foods 27 , 27 , 28 micro 27 , 30 and 29 - 30 and 30 and 31 macronutrients 30 and 34 proposed 32 already 34 proposed 33 separately 34 proposed 35 as 41 and 36 potential 38 factors 37 protective 38 factors 38 factors 39 against 38 factors 41 and 39 against 40 dementia 41 and 43 syndromes 41 and 44 . 42 predementia 43 syndromes in fact , elevated saturated fatty acids could have negative effects on age - related cognitive [decline] and mild cognitive impairment ( mci ) . 0 ###LEFT-WALL### 7 acids 0 ###LEFT-WALL### 9 have 0 ###LEFT-WALL### 15 related 1 in 2 fact 2 fact 3 , 2 fact 7 acids 4 elevated 7 acids 5 saturated 7 acids 6 fatty 7 acids 7 acids 8 could 8 could 9 have 9 have 11 effects 9 have 12 on 10 negative 11 effects 12 on 13 age 14 - 15 related 15 related 21 impairment 15 related 25 . 16 cognitive 18 and 18 and 19 mild 18 and 21 impairment 20 cognitive 21 impairment 21 impairment 23 mci 22 ( 23 mci 23 mci 24 ) furthermore , at present , epidemiological evidence suggested a possible association among fish consumption , monounsaturated fatty acids and polyunsaturated fatty acids ( pufa ) ( particularly [,] n - 3 pufa ) and reduced risk of cognitive decline [and] dementia . 0 ###LEFT-WALL### 7 evidence 0 ###LEFT-WALL### 15 , 0 ###LEFT-WALL### 42 . 1 furthermore 7 evidence 2 , 4 present 3 at 4 present 4 present 5 , 4 present 7 evidence 6 epidemiological 7 evidence 7 evidence 15 , 8 suggested 11 association 8 suggested 12 among 8 suggested 15 , 9 a 11 association 10 possible 11 association 12 among 14 consumption 13 fish 14 consumption 15 , 34 and 16 monounsaturated 19 and 16 monounsaturated 34 and 17 fatty 18 acids 18 acids 19 and 19 and 22 acids 19 and 24 pufa 19 and 32 pufa 20 polyunsaturated 22 acids 21 fatty 22 acids 23 ( 24 pufa 24 pufa 25 ) 26 ( 27 particularly 26 ( 32 pufa 29 n 30 - 30 - 31 3 30 - 32 pufa 32 pufa 33 ) 34 and 35 reduced 35 reduced 36 risk 36 risk 37 of 37 of 41 dementia 38 cognitive 39 decline 39 decline 41 dementia light to moderate alcohol use may be associated with a reduced risk of incident dementia and alzheimer 's disease ( ad ) , while for vascular dementia , cognitive decline , and predementia syndromes the current evidence is only [suggestive] of a protective effect . 0 ###LEFT-WALL### 1 light 0 ###LEFT-WALL### 8 associated 0 ###LEFT-WALL### 23 , 0 ###LEFT-WALL### 45 . 1 light 2 to 1 light 8 associated 2 to 4 alcohol 3 moderate 4 alcohol 4 alcohol 5 use 4 alcohol 7 be 5 use 6 may 6 may 7 be 8 associated 9 with 9 with 12 risk 10 a 12 risk 11 reduced 12 risk 12 risk 13 of 13 of 16 and 14 incident 15 dementia 15 dementia 16 and 16 and 19 disease 16 and 21 ad 17 alzheimer 18 's 18 's 19 disease 20 ( 21 ad 21 ad 22 ) 23 , 37 evidence 23 , 38 is 24 while 25 for 24 while 37 evidence 25 for 32 and 26 vascular 27 dementia 27 dementia 28 , 28 , 30 decline 28 , 32 and 29 cognitive 30 decline 31 , 32 and 32 and 34 syndromes 33 predementia 34 syndromes 35 the 37 evidence 36 current 37 evidence 37 evidence 38 is 38 is 39 only 38 is 41 of 41 of 44 effect 42 a 43 protective 42 a 44 effect 43 protective 44 effect finally , the limited epidemiological evidence available on fruit and vegetable consumption and cognition generally supported a protective role of these macronutrients against cognitive decline [,] dementia , and ad . 0 ###LEFT-WALL### 6 evidence 0 ###LEFT-WALL### 16 supported 0 ###LEFT-WALL### 31 . 1 finally 2 , 1 finally 6 evidence 3 the 6 evidence 4 limited 6 evidence 5 epidemiological 6 evidence 6 evidence 7 available 6 evidence 16 supported 7 available 8 on 7 available 15 generally 8 on 13 and 9 fruit 10 and 10 and 12 consumption 10 and 13 and 11 vegetable 12 consumption 13 and 14 cognition 16 supported 19 role 16 supported 23 against 17 a 18 protective 17 a 19 role 18 protective 19 role 19 role 20 of 20 of 22 macronutrients 21 these 22 macronutrients 23 against 29 and 24 cognitive 25 decline 25 decline 27 dementia 27 dementia 29 and 28 , 29 and 29 and 30 ad moreover , recent prospective studies provided evidence that higher adherence to a mediterranean [-] type diet could be associated with slower cognitive decline , reduced risk of progression from mci to ad , reduced risk of ad , and [decreased] all - causes mortality in ad patients . 0 ###LEFT-WALL### 5 studies 0 ###LEFT-WALL### 7 evidence 1 moreover 2 , 1 moreover 5 studies 3 recent 5 studies 4 prospective 5 studies 5 studies 6 provided 5 studies 7 evidence 7 evidence 10 adherence 7 evidence 11 to 8 that 10 adherence 9 higher 10 adherence 11 to 13 mediterranean 12 a 13 mediterranean 13 mediterranean 16 diet 13 mediterranean 25 reduced 15 type 16 diet 16 diet 17 could 17 could 24 , 18 be 19 associated 18 be 24 , 19 associated 20 with 20 with 23 decline 21 slower 23 decline 22 cognitive 23 decline 24 , 25 reduced 25 reduced 26 risk 26 risk 27 of 27 of 28 progression 28 progression 29 from 28 progression 31 to 29 from 30 mci 31 to 39 and 32 ad 35 risk 32 ad 39 and 33 , 35 risk 34 reduced 35 risk 35 risk 36 of 35 risk 38 , 36 of 37 ad 39 and 41 all 39 and 44 mortality 42 - 44 mortality 43 causes 44 mortality 44 mortality 45 in 44 mortality 48 . 45 in 47 patients 46 ad 47 patients these findings suggested that adherence to the medi may affect [not] only the risk for ad , but also for predementia syndromes and their progression to overt dementia . 0 ###LEFT-WALL### 2 findings 0 ###LEFT-WALL### 3 suggested 0 ###LEFT-WALL### 29 . 1 these 2 findings 2 findings 3 suggested 3 suggested 5 adherence 3 suggested 10 affect 4 that 5 adherence 5 adherence 6 to 5 adherence 9 may 6 to 8 medi 7 the 8 medi 9 may 10 affect 10 affect 12 only 10 affect 14 risk 10 affect 18 but 10 affect 26 to 13 the 14 risk 15 for 16 ad 15 for 18 but 17 , 18 but 18 but 19 also 18 but 20 for 20 for 23 and 21 predementia 22 syndromes 22 syndromes 23 and 23 and 25 progression 24 their 25 progression 26 to 28 dementia 27 overt 28 dementia nonetheless , at present , no definitive dietary recommendations are possible . 0 ###LEFT-WALL### 9 recommendations 0 ###LEFT-WALL### 10 are 0 ###LEFT-WALL### 12 . 1 nonetheless 2 , 1 nonetheless 9 recommendations 2 , 4 present 3 at 4 present 4 present 5 , 4 present 9 recommendations 6 no 9 recommendations 7 definitive 9 recommendations 8 dietary 9 recommendations 9 recommendations 10 are 10 are 11 possible however , high levels of consumption of fats [from] fish , [vegetable] oils , [non] - starchy vegetables , low glycemic fruits , and diet low in foods [with] added sugars and with moderate wine intake should be encouraged . 0 ###LEFT-WALL### 4 levels 0 ###LEFT-WALL### 10 fish 0 ###LEFT-WALL### 11 , 0 ###LEFT-WALL### 40 . 1 however 2 , 1 however 4 levels 3 high 4 levels 4 levels 5 of 4 levels 10 fish 5 of 6 consumption 6 consumption 7 of 7 of 8 fats 11 , 14 , 11 , 32 and 13 oils 14 , 14 , 31 sugars 16 - 30 added 17 starchy 18 vegetables 18 vegetables 19 , 19 , 22 fruits 19 , 24 and 20 low 22 fruits 21 glycemic 22 fruits 23 , 24 and 24 and 25 diet 24 and 26 low 24 and 30 added 26 low 27 in 27 in 28 foods 30 added 31 sugars 32 and 36 intake 32 and 39 encouraged 33 with 35 wine 33 with 36 intake 34 moderate 35 wine 36 intake 37 should 37 should 38 be 38 be 39 encouraged in fact , this dietary advice is in accordance with recommendations for lowering the risk of cardiovascular disease , obesity , diabetes , and hypertension and might open new ways for the prevention and management of cognitive decline [and] dementia . 0 ###LEFT-WALL### 6 advice 0 ###LEFT-WALL### 26 and 0 ###LEFT-WALL### 41 . 1 in 2 fact 2 fact 3 , 2 fact 6 advice 4 this 5 dietary 5 dietary 6 advice 6 advice 26 and 7 is 8 in 7 is 10 with 7 is 26 and 8 in 9 accordance 10 with 24 and 11 recommendations 12 for 11 recommendations 19 , 12 for 13 lowering 13 lowering 15 risk 14 the 15 risk 15 risk 16 of 16 of 18 disease 17 cardiovascular 18 disease 19 , 20 obesity 19 , 21 , 21 , 22 diabetes 21 , 24 and 23 , 24 and 24 and 25 hypertension 26 and 27 might 27 might 28 open 28 open 30 ways 28 open 31 for 29 new 30 ways 31 for 34 and 32 the 33 prevention 33 prevention 34 and 34 and 35 management 34 and 36 of 36 of 40 dementia 37 cognitive 38 decline 38 decline 40 dementia the anomalous aggregation of proteins into pathological filaments is a common feature of [a] many human diseases , often related to aging . 0 ###LEFT-WALL### 3 aggregation 0 ###LEFT-WALL### 18 , 0 ###LEFT-WALL### 23 . 1 the 3 aggregation 2 anomalous 3 aggregation 3 aggregation 4 of 3 aggregation 18 , 4 of 5 proteins 5 proteins 6 into 6 into 8 filaments 7 pathological 8 filaments 9 is 12 feature 9 is 18 , 10 a 11 common 10 a 12 feature 11 common 12 feature 12 feature 13 of 13 of 17 diseases 15 many 17 diseases 16 human 17 diseases 18 , 20 related 18 , 21 to 19 often 20 related 21 to 22 aging in this context , neurodegenerative pathologies such as alzheimer 's disease ( ad ) account for a major part of these protein misfolding diseases . 0 ###LEFT-WALL### 6 pathologies 0 ###LEFT-WALL### 15 account 0 ###LEFT-WALL### 25 . 1 in 3 context 1 in 4 , 1 in 6 pathologies 2 this 3 context 5 neurodegenerative 6 pathologies 6 pathologies 8 as 6 pathologies 15 account 7 such 8 as 8 as 11 disease 9 alzheimer 10 's 10 's 11 disease 11 disease 13 ad 12 ( 13 ad 13 ad 14 ) 15 account 16 for 16 for 24 diseases 17 a 18 major 17 a 19 part 18 major 19 part 19 part 20 of 19 part 24 diseases 20 of 24 diseases 21 these 24 diseases 22 protein 23 misfolding 23 misfolding 24 diseases ad is characterized by pathological aggregation of two proteins , tau and aβ - amyloid . 0 ###LEFT-WALL### 1 ad 0 ###LEFT-WALL### 3 characterized 0 ###LEFT-WALL### 14 - 0 ###LEFT-WALL### 16 . 1 ad 2 is 2 is 3 characterized 3 characterized 4 by 4 by 6 aggregation 5 pathological 6 aggregation 6 aggregation 7 of 7 of 12 and 8 two 9 proteins 9 proteins 10 , 10 , 11 tau 10 , 12 and 12 and 13 aβ 14 - 15 amyloid the intracellular neurofibrillary tangles ( nfts [ )(and neuropil threads [consists] of filaments of the modified microtubule - associated protein tau , while extracellular amyloid [plaques] consists of filaments of aβ - peptide . 0 ###LEFT-WALL### 4 tangles 0 ###LEFT-WALL### 19 associated 0 ###LEFT-WALL### 32 - 1 the 4 tangles 2 intracellular 4 tangles 3 neurofibrillary 4 tangles 4 tangles 8 )(and 4 tangles 19 associated 5 ( 8 )(and 6 nfts 8 )(and 8 )(and 10 threads 8 )(and 12 of 8 )(and 18 - 9 neuropil 10 threads 12 of 13 filaments 13 filaments 14 of 14 of 17 microtubule 15 the 17 microtubule 16 modified 17 microtubule 19 associated 21 tau 19 associated 23 while 20 protein 21 tau 22 , 23 while 23 while 25 amyloid 23 while 27 consists 23 while 32 - 24 extracellular 25 amyloid 25 amyloid 27 consists 27 consists 28 of 28 of 29 filaments 29 filaments 30 of 30 of 31 aβ 32 - 33 peptide 32 - 34 . it is [noteworthy] that tau oligomers with a prefilamentous structure appear to play a role at early stages of ad and tauopathies , but also in asymptomatic patients with braak - stage i neuropathology , where clinical symptoms of ad and nfts [in] frontal cortex are absent . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 48 . 1 it 2 is 2 is 4 that 4 that 6 oligomers 4 that 11 appear 5 tau 6 oligomers 6 oligomers 7 with 6 oligomers 11 appear 7 with 10 structure 8 a 10 structure 9 prefilamentous 10 structure 11 appear 12 to 11 appear 24 but 12 to 13 play 13 play 15 role 14 a 15 role 16 at 18 stages 16 at 24 but 17 early 18 stages 18 stages 19 of 19 of 21 and 20 ad 21 and 21 and 22 tauopathies 21 and 23 , 23 , 24 but 24 but 25 also 24 but 26 in 26 in 28 patients 27 asymptomatic 28 patients 28 patients 29 with 28 patients 36 where 29 with 30 braak 30 braak 34 neuropathology 31 - 34 neuropathology 32 stage 33 i 32 stage 34 neuropathology 34 neuropathology 35 , 36 where 38 symptoms 36 where 46 are 37 clinical 38 symptoms 38 symptoms 39 of 38 symptoms 46 are 39 of 41 and 40 ad 41 and 41 and 45 cortex 42 nfts 45 cortex 44 frontal 45 cortex 46 are 47 absent this suggests that an increase in tau oligomers levels occurs before individuals manifest clinical symptoms of ad . 0 ###LEFT-WALL### 1 this 0 ###LEFT-WALL### 2 suggests 0 ###LEFT-WALL### 18 . 1 this 2 suggests 2 suggests 3 that 3 that 5 increase 3 that 10 occurs 4 an 5 increase 5 increase 6 in 5 increase 10 occurs 6 in 9 levels 7 tau 9 levels 8 oligomers 9 levels 10 occurs 11 before 11 before 12 individuals 11 before 13 manifest 12 individuals 13 manifest 13 manifest 15 symptoms 14 clinical 15 symptoms 15 symptoms 16 of 16 of 17 ad nfts are one of the hallmarks of alzheimer disease and other tauphaties . 0 ###LEFT-WALL### 1 nfts 0 ###LEFT-WALL### 2 are 0 ###LEFT-WALL### 13 . 1 nfts 2 are 2 are 3 one 3 one 4 of 4 of 6 hallmarks 5 the 6 hallmarks 6 hallmarks 7 of 7 of 10 and 8 alzheimer 9 disease 9 disease 10 and 10 and 12 tauphaties 11 other 12 tauphaties these aggregates are thought to be toxic to neurons [,] either by causing some neurotoxic signalling defects or by obstructing the cell function . 0 ###LEFT-WALL### 2 aggregates 0 ###LEFT-WALL### 4 thought 0 ###LEFT-WALL### 24 . 1 these 2 aggregates 2 aggregates 3 are 3 are 4 thought 4 thought 5 to 5 to 6 be 6 be 7 toxic 7 toxic 8 to 8 to 9 neurons 9 neurons 18 or 11 either 18 or 12 by 13 causing 12 by 18 or 13 causing 17 defects 14 some 17 defects 15 neurotoxic 17 defects 16 signalling 17 defects 18 or 19 by 19 by 20 obstructing 20 obstructing 23 function 21 the 23 function 22 cell 23 function factors contributing to accumulation of tau aggregates include the increased rate of protein misfolding , generation of amyloidogenic oligomers , [underactivity] of repair systems such as [chaperones] [and] ubiquitin - proteasome system , or a failure of energy supply and antioxidant defense mechanisms . 0 ###LEFT-WALL### 1 factors 0 ###LEFT-WALL### 8 include 1 factors 2 contributing 1 factors 3 to 1 factors 5 of 1 factors 8 include 3 to 4 accumulation 5 of 7 aggregates 6 tau 7 aggregates 8 include 11 rate 9 the 11 rate 10 increased 11 rate 11 rate 12 of 11 rate 22 of 12 of 13 protein 13 protein 14 misfolding 13 protein 16 generation 15 , 16 generation 16 generation 17 of 16 generation 20 , 17 of 19 oligomers 18 amyloidogenic 19 oligomers 22 of 24 systems 23 repair 24 systems 24 systems 26 as 24 systems 34 or 25 such 26 as 26 as 29 ubiquitin 30 - 34 or 31 proteasome 32 system 32 system 34 or 33 , 34 or 34 or 43 mechanisms 34 or 44 . 35 a 36 failure 36 failure 37 of 36 failure 40 and 37 of 39 supply 38 energy 39 supply 40 and 41 antioxidant 40 and 42 defense 42 defense 43 mechanisms there is not clear evidence if the aggregated tau or oligomers cause cellular damage , but on the basis of the emergent need to have an early and effective treatment , lowering the production or removal of these aggregates appears as a pathway toward alleviating the disease . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 31 , 0 ###LEFT-WALL### 48 . 1 there 2 is 2 is 3 not 2 is 5 evidence 2 is 6 if 2 is 16 but 3 not 4 clear 4 clear 5 evidence 6 if 10 or 6 if 12 cause 7 the 9 tau 8 aggregated 9 tau 9 tau 10 or 10 or 11 oligomers 10 or 12 cause 12 cause 14 damage 13 cellular 14 damage 15 , 16 but 16 but 17 on 16 but 31 , 17 on 19 basis 18 the 19 basis 19 basis 20 of 20 of 23 need 21 the 23 need 22 emergent 23 need 23 need 24 to 23 need 25 have 24 to 25 have 25 have 30 treatment 26 an 30 treatment 27 early 28 and 28 and 29 effective 28 and 30 treatment 31 , 32 lowering 31 , 40 appears 32 lowering 35 or 32 lowering 40 appears 33 the 34 production 34 production 35 or 35 or 36 removal 35 or 37 of 37 of 39 aggregates 38 these 39 aggregates 40 appears 41 as 40 appears 44 toward 41 as 43 pathway 42 a 43 pathway 44 toward 45 alleviating 45 alleviating 47 disease 46 the 47 disease in the context of some of most relevant reports , we analyze why tau protein seems to be an interesting target for ad treatment , and the importance to understand the pathways of tau . aggregation . 0 ###LEFT-WALL### 11 we 0 ###LEFT-WALL### 12 analyze 0 ###LEFT-WALL### 35 . 1 in 3 context 1 in 10 , 1 in 11 we 2 the 3 context 3 context 4 of 4 of 5 some 5 some 6 of 6 of 9 reports 7 most 8 relevant 8 relevant 9 reports 11 we 12 analyze 12 analyze 13 why 12 analyze 29 to 13 why 15 protein 13 why 16 seems 14 tau 15 protein 15 protein 16 seems 16 seems 17 to 16 seems 18 be 17 to 18 be 18 be 21 target 19 an 20 interesting 19 an 21 target 20 interesting 21 target 21 target 22 for 22 for 26 and 23 ad 24 treatment 24 treatment 26 and 25 , 26 and 26 and 28 importance 27 the 28 importance 29 to 30 understand 30 understand 32 pathways 31 the 32 pathways 32 pathways 33 of 33 of 34 tau 35 . 36 aggregation 35 . 37 . this knowledge will allow us [to] [identify] and optimize potential inhibitors that interact with aggregated forms of tau and hyperphosphorylated tau before the formation of the nfts , offering a possible therapeutic route for ad treatment . 0 ###LEFT-WALL### 2 knowledge 0 ###LEFT-WALL### 8 and 1 this 2 knowledge 2 knowledge 3 will 3 will 8 and 4 allow 5 us 4 allow 8 and 8 and 19 and 9 optimize 11 inhibitors 9 optimize 14 with 9 optimize 19 and 10 potential 11 inhibitors 11 inhibitors 12 that 11 inhibitors 13 interact 12 that 13 interact 14 with 16 forms 15 aggregated 16 forms 16 forms 17 of 17 of 18 tau 19 and 20 hyperphosphorylated 20 hyperphosphorylated 21 tau 21 tau 22 before 21 tau 25 of 22 before 24 formation 23 the 24 formation 25 of 27 nfts 26 the 27 nfts 27 nfts 29 offering 28 , 29 offering 29 offering 33 route 29 offering 36 treatment 29 offering 37 . 30 a 31 possible 30 a 33 route 31 possible 33 route 32 therapeutic 33 route 33 route 34 for 34 for 35 ad altered proteolytic processing of the β - amyloid precursor protein ( app ) is a central event in familial and sporadic alzheimer 's disease ( ad ) . 0 ###LEFT-WALL### 3 processing 0 ###LEFT-WALL### 14 is 0 ###LEFT-WALL### 28 . 1 altered 3 processing 2 proteolytic 3 processing 3 processing 4 of 3 processing 14 is 4 of 10 protein 5 the 10 protein 6 β 7 - 6 β 8 amyloid 8 amyloid 9 precursor 9 precursor 10 protein 10 protein 12 app 11 ( 12 app 12 app 13 ) 14 is 17 event 15 a 16 central 15 a 17 event 16 central 17 event 17 event 18 in 18 in 24 disease 19 familial 20 and 20 and 21 sporadic 20 and 22 alzheimer 22 alzheimer 23 's 23 's 24 disease 24 disease 26 ad 25 ( 26 ad 26 ad 27 ) in a process termed regulated intramembrane proteolysis ( rip ) , app first undergoes ectodomain shedding executed either by α - secretases at the plasma membrane or by β - secretase in the endosomal compartment . 0 ###LEFT-WALL### 12 app 0 ###LEFT-WALL### 14 undergoes 0 ###LEFT-WALL### 36 . 1 in 3 process 1 in 11 , 1 in 12 app 2 a 3 process 3 process 4 termed 4 termed 7 proteolysis 5 regulated 7 proteolysis 6 intramembrane 7 proteolysis 7 proteolysis 9 rip 8 ( 9 rip 9 rip 10 ) 12 app 14 undergoes 13 first 14 undergoes 14 undergoes 16 shedding 14 undergoes 27 or 15 ectodomain 16 shedding 16 shedding 17 executed 18 either 27 or 19 by 22 secretases 19 by 27 or 20 α 21 - 20 α 22 secretases 22 secretases 23 at 23 at 26 membrane 24 the 26 membrane 25 plasma 26 membrane 27 or 28 by 28 by 31 secretase 29 β 30 - 29 β 31 secretase 31 secretase 32 in 32 in 35 compartment 33 the 35 compartment 34 endosomal 35 compartment the remaining membrane - anchored stubs are cleaved within the membrane plane by the [γ] [-] secretase complex , releasing the app intracellular domain ( aicd ) into the cytosol and leading to the generation of the aβ peptide in the amyloidogenic pathway that is initiated by β - secretase . 0 ###LEFT-WALL### 3 membrane 0 ###LEFT-WALL### 4 - 1 the 2 remaining 1 the 3 membrane 4 - 6 stubs 4 - 8 cleaved 5 anchored 6 stubs 6 stubs 7 are 7 are 8 cleaved 8 cleaved 9 within 8 cleaved 13 by 8 cleaved 18 complex 9 within 12 plane 10 the 12 plane 11 membrane 12 plane 13 by 17 secretase 14 the 17 secretase 18 complex 20 releasing 19 , 20 releasing 20 releasing 24 domain 20 releasing 28 into 21 the 24 domain 22 app 24 domain 23 intracellular 24 domain 24 domain 26 aicd 25 ( 26 aicd 26 aicd 27 ) 28 into 31 and 29 the 30 cytosol 30 cytosol 31 and 31 and 32 leading 32 leading 33 to 33 to 35 generation 34 the 35 generation 35 generation 36 of 35 generation 40 in 36 of 39 peptide 37 the 39 peptide 38 aβ 39 peptide 40 in 43 pathway 41 the 43 pathway 42 amyloidogenic 43 pathway 43 pathway 44 that 43 pathway 45 is 44 that 45 is 45 is 46 initiated 46 initiated 47 by 47 by 48 β 48 β 50 secretase 49 - 50 secretase 50 secretase 51 . the aβ peptides aggregate to form soluble oligomers and finally deposit into amyloid plaques that are a hallmark of ad . 0 ###LEFT-WALL### 3 peptides 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 21 . 1 the 3 peptides 2 aβ 3 peptides 3 peptides 9 and 4 aggregate 5 to 4 aggregate 9 and 5 to 6 form 6 form 8 oligomers 7 soluble 8 oligomers 9 and 11 deposit 9 and 12 into 10 finally 11 deposit 12 into 14 plaques 13 amyloid 14 plaques 14 plaques 15 that 14 plaques 16 are 15 that 16 are 16 are 18 hallmark 17 a 18 hallmark 18 hallmark 19 of 19 of 20 ad recent evidence indicates a role for aβ oligomers in regulating synaptic plasticity with excess amounts of oligomers disrupting synaptic [function] . 0 ###LEFT-WALL### 2 evidence 0 ###LEFT-WALL### 3 indicates 0 ###LEFT-WALL### 21 . 1 recent 2 evidence 2 evidence 3 indicates 3 indicates 5 role 3 indicates 8 oligomers 4 a 5 role 5 role 6 for 5 role 8 oligomers 6 for 7 aβ 8 oligomers 9 in 9 in 10 regulating 10 regulating 12 plasticity 10 regulating 13 with 11 synaptic 12 plasticity 13 with 15 amounts 13 with 19 synaptic 14 excess 15 amounts 15 amounts 16 of 16 of 18 disrupting 17 oligomers 18 disrupting the amyloid cascade hypothesis of ad is centered on the aβ peptide , the app fragment that has been most intensely studied , while other cleavage products have been largely neglected . 0 ###LEFT-WALL### 4 hypothesis 0 ###LEFT-WALL### 32 . 1 the 4 hypothesis 2 amyloid 4 hypothesis 3 cascade 4 hypothesis 4 hypothesis 5 of 4 hypothesis 7 is 5 of 6 ad 7 is 8 centered 8 centered 9 on 8 centered 24 while 9 on 12 peptide 10 the 12 peptide 11 aβ 12 peptide 12 peptide 16 fragment 13 , 16 fragment 14 the 16 fragment 15 app 16 fragment 16 fragment 17 that 16 fragment 18 has 16 fragment 23 , 17 that 18 has 18 has 19 been 19 been 22 studied 20 most 21 intensely 21 intensely 22 studied 24 while 27 products 24 while 31 neglected 25 other 27 products 26 cleavage 27 products 27 products 28 have 28 have 29 been 29 been 31 neglected 30 largely 31 neglected the secreted ectodomain generated [after] α - cleavage in the [non] [-] amyloidogenic pathway has neurotrophic and neuroproliferative activities , thus opposing the neurotoxicity observed with high concentrations of aβ . 0 ###LEFT-WALL### 8 cleavage 0 ###LEFT-WALL### 15 has 0 ###LEFT-WALL### 25 observed 1 the 8 cleavage 2 secreted 3 ectodomain 3 ectodomain 4 generated 4 generated 8 cleavage 6 α 7 - 6 α 8 cleavage 8 cleavage 9 in 8 cleavage 15 has 9 in 14 pathway 10 the 14 pathway 13 amyloidogenic 14 pathway 15 has 19 activities 16 neurotrophic 17 and 17 and 18 neuroproliferative 17 and 19 activities 20 , 25 observed 21 thus 22 opposing 22 opposing 24 neurotoxicity 22 opposing 25 observed 23 the 24 neurotoxicity 25 observed 26 with 25 observed 31 . 26 with 28 concentrations 27 high 28 concentrations 28 concentrations 29 of 29 of 30 aβ further , in analogy to many other membrane proteins that are subject to rip , aicd can translocate to the nucleus to regulate transcription . 0 ###LEFT-WALL### 16 aicd 0 ###LEFT-WALL### 18 translocate 0 ###LEFT-WALL### 25 . 1 further 2 , 1 further 16 aicd 2 , 3 in 3 in 4 analogy 3 in 15 , 3 in 16 aicd 4 analogy 5 to 4 analogy 13 to 5 to 9 proteins 6 many 7 other 7 other 9 proteins 8 membrane 9 proteins 9 proteins 10 that 9 proteins 11 are 10 that 11 are 11 are 12 subject 13 to 14 rip 16 aicd 17 can 17 can 18 translocate 18 translocate 19 to 18 translocate 24 transcription 19 to 21 nucleus 20 the 21 nucleus 21 nucleus 22 to 21 nucleus 23 regulate 22 to 23 regulate many rip substrates are localized to [the] synapse [and] thus could convey a direct signal from [the] synapse [to] the nucleus [upon] cleavage . 0 ###LEFT-WALL### 1 many 0 ###LEFT-WALL### 18 synapse 0 ###LEFT-WALL### 24 . 1 many 2 rip 1 many 16 from 1 many 18 synapse 2 rip 3 substrates 2 rip 8 synapse 2 rip 11 could 3 substrates 4 are 4 are 5 localized 5 localized 6 to 6 to 8 synapse 10 thus 11 could 11 could 12 convey 12 convey 15 signal 12 convey 16 from 13 a 14 direct 13 a 15 signal 14 direct 15 signal 18 synapse 23 cleavage 20 the 23 cleavage 21 nucleus 23 cleavage evidence indicates that only the amyloidogenic pathway generates aicd capable of nuclear signaling , due to the subcellular compartmentalization of app processing . 0 ###LEFT-WALL### 1 evidence 0 ###LEFT-WALL### 2 indicates 1 evidence 2 indicates 2 indicates 3 that 3 that 4 only 3 that 7 pathway 3 that 8 generates 5 the 7 pathway 6 amyloidogenic 7 pathway 7 pathway 8 generates 8 generates 9 aicd 9 aicd 10 capable 10 capable 11 of 10 capable 16 to 11 of 13 signaling 12 nuclear 13 signaling 14 , 16 to 15 due 16 to 16 to 19 compartmentalization 16 to 23 . 17 the 19 compartmentalization 18 subcellular 19 compartmentalization 19 compartmentalization 20 of 20 of 22 processing 21 app 22 processing in aging and sporadic ad there is an increase in β - secretase levels and activity generating more aβ peptides [and] concomitantly leading to an increase in aicd nuclear signaling . 0 ###LEFT-WALL### 1 in 0 ###LEFT-WALL### 7 is 0 ###LEFT-WALL### 31 . 1 in 5 ad 1 in 7 is 2 aging 3 and 3 and 4 sporadic 3 and 5 ad 5 ad 6 there 7 is 9 increase 8 an 9 increase 9 increase 10 in 9 increase 17 generating 9 increase 23 leading 10 in 15 and 11 β 12 - 11 β 13 secretase 13 secretase 14 levels 14 levels 15 and 15 and 16 activity 17 generating 20 peptides 18 more 20 peptides 19 aβ 20 peptides 22 concomitantly 23 leading 23 leading 24 to 23 leading 27 in 24 to 26 increase 25 an 26 increase 27 in 30 signaling 28 aicd 30 signaling 29 nuclear 30 signaling in this review , i summarize the current knowledge on aicd nuclear signaling and propose mechanisms to explain how this physiological function of app might impact the pathology seen in ad . 0 ###LEFT-WALL### 5 i 0 ###LEFT-WALL### 14 and 0 ###LEFT-WALL### 32 . 1 in 3 review 1 in 4 , 1 in 5 i 2 this 3 review 5 i 14 and 6 summarize 9 knowledge 6 summarize 10 on 6 summarize 14 and 7 the 9 knowledge 8 current 9 knowledge 10 on 13 signaling 11 aicd 13 signaling 12 nuclear 13 signaling 14 and 15 propose 15 propose 16 mechanisms 15 propose 17 to 15 propose 30 in 17 to 18 explain 18 explain 19 how 19 how 22 function 19 how 26 impact 20 this 22 function 21 physiological 22 function 22 function 23 of 22 function 25 might 23 of 24 app 25 might 26 impact 26 impact 28 pathology 27 the 28 pathology 28 pathology 29 seen 30 in 31 ad alzheimer 's disease ( ad ) is the most common cause of dementia in aging populations . 0 ###LEFT-WALL### 3 disease 0 ###LEFT-WALL### 7 is 0 ###LEFT-WALL### 17 . 1 alzheimer 2 's 2 's 3 disease 3 disease 5 ad 3 disease 7 is 4 ( 5 ad 5 ad 6 ) 7 is 11 cause 8 the 11 cause 9 most 10 common 10 common 11 cause 11 cause 12 of 12 of 13 dementia 13 dementia 14 in 14 in 15 aging 15 aging 16 populations although amyloid plaques are the hallmark of ad , loss [of] [synapses] and synaptic dysfunction are closely associated with the duration and severity of cognitive impairment in ad patients . 0 ###LEFT-WALL### 3 plaques 0 ###LEFT-WALL### 4 are 0 ###LEFT-WALL### 9 , 0 ###LEFT-WALL### 30 . 1 although 2 amyloid 1 although 3 plaques 3 plaques 4 are 4 are 6 hallmark 5 the 6 hallmark 6 hallmark 7 of 7 of 8 ad 9 , 13 and 9 , 18 associated 10 loss 13 and 13 and 15 dysfunction 13 and 16 are 14 synaptic 15 dysfunction 16 are 17 closely 16 are 18 associated 18 associated 19 with 18 associated 27 in 19 with 22 and 20 the 21 duration 21 duration 22 and 22 and 23 severity 22 and 24 of 24 of 26 impairment 25 cognitive 26 impairment 27 in 29 patients 28 ad 29 patients amyloid precursor protein ( app [ )(and its cleavage products including aβ have been suggested as homeostatic regulators of synaptic activity . 0 ###LEFT-WALL### 3 protein 0 ###LEFT-WALL### 15 suggested 1 amyloid 3 protein 2 precursor 3 protein 4 ( 15 suggested 5 app 7 )(and 7 )(and 9 cleavage 7 )(and 10 products 7 )(and 14 been 7 )(and 15 suggested 8 its 9 cleavage 10 products 11 including 10 products 13 have 11 including 12 aβ 13 have 14 been 15 suggested 16 as 15 suggested 22 . 16 as 18 regulators 17 homeostatic 18 regulators 18 regulators 19 of 19 of 21 activity 20 synaptic 21 activity app manipulation and aβ application , in vitro [and] in vivo [,] affect synapse formation and synaptic transmission . 0 ###LEFT-WALL### 1 app 0 ###LEFT-WALL### 14 synapse 0 ###LEFT-WALL### 19 . 1 app 3 and 1 app 13 affect 1 app 14 synapse 2 manipulation 3 and 3 and 5 application 3 and 6 , 3 and 13 affect 4 aβ 5 application 7 in 8 vitro 8 vitro 13 affect 10 in 11 vivo 11 vivo 13 affect 14 synapse 16 and 15 formation 16 and 16 and 18 transmission 17 synaptic 18 transmission moreover , synaptic dysfunction and learning deficits precede aβ plaque deposition , suggesting that synaptic alterations may underlie the initial development of the disease . 0 ###LEFT-WALL### 5 and 0 ###LEFT-WALL### 12 , 0 ###LEFT-WALL### 25 . 1 moreover 2 , 1 moreover 5 and 3 synaptic 4 dysfunction 4 dysfunction 5 and 5 and 7 deficits 5 and 12 , 6 learning 7 deficits 8 precede 11 deposition 8 precede 12 , 9 aβ 11 deposition 10 plaque 11 deposition 12 , 18 underlie 13 suggesting 16 alterations 13 suggesting 17 may 14 that 15 synaptic 15 synaptic 16 alterations 17 may 18 underlie 18 underlie 21 development 19 the 21 development 20 initial 21 development 21 development 22 of 22 of 24 disease 23 the 24 disease because of the pivotal role of app and aβ in ad pathogenesis , it is essential to understand how app and aβ modulate [synaptic] function . 0 ###LEFT-WALL### 25 function 0 ###LEFT-WALL### 26 . 1 because 2 of 1 because 25 function 2 of 8 and 3 the 5 role 4 pivotal 5 role 5 role 6 of 5 role 8 and 6 of 7 app 8 and 9 aβ 8 and 13 , 8 and 14 it 8 and 23 modulate 9 aβ 10 in 10 in 12 pathogenesis 11 ad 12 pathogenesis 14 it 15 is 15 is 16 essential 16 essential 17 to 16 essential 23 modulate 17 to 18 understand 18 understand 19 how 20 app 21 and 21 and 22 aβ 21 and 23 modulate here , we review the roles that app and aβ play [at] [the] synapses , with particular focus on recent findings for the importance of app in synaptogenesis and synaptic function . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 review 1 here 2 , 1 here 3 we 3 we 4 review 4 review 6 roles 5 the 6 roles 6 roles 7 that 6 roles 14 synapses 7 that 11 play 7 that 14 synapses 8 app 9 and 9 and 10 aβ 10 aβ 11 play 11 play 14 synapses 14 synapses 16 with 15 , 16 with 16 with 18 focus 16 with 22 for 16 with 32 . 17 particular 18 focus 18 focus 19 on 19 on 21 findings 20 recent 21 findings 22 for 24 importance 23 the 24 importance 24 importance 25 of 25 of 26 app 26 app 27 in 27 in 29 and 28 synaptogenesis 29 and 29 and 31 function 30 synaptic 31 function in response to a thermal stress , skin blood flow ( bf ) increases to protect the skin from damage . 0 ###LEFT-WALL### 10 flow 0 ###LEFT-WALL### 14 increases 0 ###LEFT-WALL### 21 . 1 in 2 response 2 response 3 to 3 to 6 stress 3 to 7 , 3 to 10 flow 4 a 5 thermal 4 a 6 stress 5 thermal 6 stress 8 skin 10 flow 9 blood 10 flow 10 flow 12 bf 10 flow 14 increases 11 ( 12 bf 12 bf 13 ) 14 increases 15 to 15 to 16 protect 16 protect 18 skin 17 the 18 skin 18 skin 19 from 19 from 20 damage when a very warm , noxious , heat source ( 44 °c ) is applied to the skin , the bf increases disproportionately faster than the heat stress that was applied , creating a safety mechanism for protecting the skin . 0 ###LEFT-WALL### 22 increases 0 ###LEFT-WALL### 28 stress 1 when 9 source 1 when 15 applied 1 when 19 , 1 when 22 increases 2 a 3 very 2 a 9 source 3 very 4 warm 4 warm 5 , 4 warm 8 heat 6 noxious 7 , 6 noxious 8 heat 8 heat 9 source 9 source 12 °c 9 source 14 is 10 ( 12 °c 11 44 12 °c 12 °c 13 ) 14 is 15 applied 15 applied 16 to 16 to 18 skin 17 the 18 skin 20 the 22 increases 21 bf 22 increases 22 increases 24 faster 22 increases 28 stress 23 disproportionately 24 faster 24 faster 25 than 25 than 27 heat 26 the 27 heat 28 stress 29 that 28 stress 31 applied 29 that 30 was 30 was 31 applied 31 applied 33 creating 32 , 33 creating 33 creating 36 mechanism 33 creating 41 . 34 a 36 mechanism 35 safety 36 mechanism 36 mechanism 37 for 37 for 38 protecting 38 protecting 40 skin 39 the 40 skin twenty male and female subjects ( 10 - 20 - 35 years , 10 - 40 - 70 years ) were examined . 0 ###LEFT-WALL### 5 subjects 0 ###LEFT-WALL### 21 were 0 ###LEFT-WALL### 23 . 1 twenty 5 subjects 2 male 3 and 3 and 4 female 3 and 5 subjects 5 subjects 8 - 5 subjects 15 - 5 subjects 21 were 6 ( 8 - 7 10 8 - 8 - 12 years 8 - 13 , 9 20 10 - 10 - 11 35 10 - 12 years 13 , 15 - 14 10 15 - 15 - 17 - 15 - 20 ) 16 40 17 - 17 - 19 years 18 70 19 years 21 were 22 examined however , the older subjects achieved similar skin temperatures but with the expenditure of fewer calories from the thermode than [was] seen for the younger subjects ( p<0.05 ) . 0 ###LEFT-WALL### 5 subjects 0 ###LEFT-WALL### 6 achieved 0 ###LEFT-WALL### 30 . 1 however 2 , 1 however 5 subjects 3 the 5 subjects 4 older 5 subjects 5 subjects 6 achieved 6 achieved 9 temperatures 6 achieved 10 but 6 achieved 17 from 7 similar 8 skin 8 skin 9 temperatures 10 but 11 with 11 with 13 expenditure 12 the 13 expenditure 13 expenditure 14 of 14 of 16 calories 15 fewer 16 calories 17 from 19 thermode 18 the 19 thermode 19 thermode 22 seen 20 than 22 seen 22 seen 23 for 23 for 26 subjects 24 the 26 subjects 25 younger 26 subjects 26 subjects 28 p<0.05 27 ( 28 p<0.05 28 p<0.05 29 ) bf was significantly less in the older group than the younger group at rest and after exposure to each of the three warmest thermode temperatures ( p<0.05 ) . 0 ###LEFT-WALL### 1 bf 0 ###LEFT-WALL### 2 was 0 ###LEFT-WALL### 29 . 1 bf 2 was 2 was 4 less 2 was 5 in 2 was 9 than 2 was 15 and 2 was 18 to 3 significantly 4 less 5 in 8 group 6 the 8 group 7 older 8 group 9 than 12 group 10 the 12 group 11 younger 12 group 13 at 14 rest 13 at 15 and 15 and 16 after 16 after 17 exposure 18 to 25 temperatures 19 each 20 of 19 each 25 temperatures 20 of 25 temperatures 21 the 22 three 22 three 23 warmest 22 three 25 temperatures 24 thermode 25 temperatures 25 temperatures 27 p<0.05 26 ( 27 p<0.05 27 p<0.05 28 ) as was seen for noxious temperatures , after a delay , the rate [of] rise of bf at the three warmest thermode temperatures was faster than the rise in skin temperature in the younger group but less in the older group of subjects . 0 ###LEFT-WALL### 15 rise 0 ###LEFT-WALL### 24 was 0 ###LEFT-WALL### 44 . 1 as 2 was 1 as 3 seen 1 as 15 rise 2 was 3 seen 3 seen 4 for 4 for 6 temperatures 5 noxious 6 temperatures 6 temperatures 8 after 7 , 8 after 8 after 10 delay 8 after 11 , 9 a 10 delay 12 the 15 rise 13 rate 15 rise 15 rise 16 of 15 rise 18 at 15 rise 24 was 16 of 17 bf 18 at 23 temperatures 19 the 20 three 20 three 21 warmest 20 three 23 temperatures 22 thermode 23 temperatures 24 was 25 faster 25 faster 26 than 25 faster 29 in 25 faster 36 but 26 than 28 rise 27 the 28 rise 29 in 31 temperature 30 skin 31 temperature 32 in 35 group 32 in 36 but 33 the 35 group 34 younger 35 group 36 but 37 less 36 but 38 in 38 in 43 subjects 39 the 41 group 40 older 41 group 41 group 42 of 41 group 43 subjects 42 of 43 subjects thus , a consequence of ageing is reduced excess bf in response to thermal stress increasing susceptibility to thermal damage . 0 ###LEFT-WALL### 4 consequence 0 ###LEFT-WALL### 7 is 0 ###LEFT-WALL### 21 . 1 thus 2 , 1 thus 4 consequence 3 a 4 consequence 4 consequence 5 of 4 consequence 7 is 5 of 6 ageing 7 is 10 bf 7 is 13 to 8 reduced 10 bf 9 excess 10 bf 11 in 12 response 12 response 13 to 13 to 15 stress 14 thermal 15 stress 15 stress 16 increasing 16 increasing 17 susceptibility 16 increasing 18 to 18 to 20 damage 19 thermal 20 damage this must be considered in modelling of bf . 0 ###LEFT-WALL### 1 this 0 ###LEFT-WALL### 4 considered 0 ###LEFT-WALL### 9 . 1 this 2 must 2 must 3 be 3 be 4 considered 4 considered 5 in 5 in 6 modelling 6 modelling 7 of 7 of 8 bf objective : epidemiological studies in children and adolescents have revealed short sleep duration as a risk factor for weight gain . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 2 : 4 studies 2 : 9 have 2 : 21 . 3 epidemiological 4 studies 4 studies 5 in 4 studies 9 have 5 in 7 and 6 children 7 and 7 and 8 adolescents 9 have 13 duration 9 have 14 as 9 have 20 gain 10 revealed 11 short 11 short 13 duration 12 sleep 13 duration 14 as 17 factor 15 a 17 factor 16 risk 17 factor 17 factor 18 for 18 for 19 weight however , only few studies have addressed sleep in early childhood . 0 ###LEFT-WALL### 3 only 0 ###LEFT-WALL### 7 addressed 0 ###LEFT-WALL### 12 . 1 however 2 , 1 however 3 only 3 only 5 studies 4 few 5 studies 5 studies 6 have 6 have 7 addressed 7 addressed 8 sleep 7 addressed 9 in 9 in 11 childhood 10 early 11 childhood our aim was to determine whether sleep in the second year of life is associated with the development of body composition throughout childhood . 0 ###LEFT-WALL### 2 aim 0 ###LEFT-WALL### 24 . 1 our 2 aim 2 aim 3 was 3 was 4 to 3 was 5 determine 4 to 5 determine 5 determine 6 whether 6 whether 7 sleep 6 whether 15 associated 7 sleep 8 in 7 sleep 14 is 8 in 11 year 9 the 11 year 10 second 11 year 11 year 12 of 12 of 13 life 14 is 15 associated 15 associated 16 with 15 associated 22 throughout 16 with 18 development 17 the 18 development 18 development 19 of 19 of 21 composition 20 body 21 composition 22 throughout 23 childhood methods : analysis included 481 donald participants with parental reported data on sleep duration and annually measured body composition until age 7 . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 23 . 1 methods 2 : 2 : 3 analysis 3 analysis 15 and 4 included 7 participants 4 included 15 and 5 481 7 participants 6 donald 7 participants 7 participants 8 with 8 with 11 data 9 parental 11 data 10 reported 11 data 11 data 12 on 12 on 14 duration 13 sleep 14 duration 15 and 17 measured 15 and 20 until 16 annually 17 measured 17 measured 19 composition 18 body 19 composition 20 until 21 age 21 age 22 7 using median splits of sleeping time at 1.5 and 2 years we defined sleep duration [categories] : consistently short ( cs , n = 122 ) , inconsistent [(] i , n = 143 ) and consistently long [(] cl , n = 216 ) . 0 ###LEFT-WALL### 3 splits 0 ###LEFT-WALL### 46 . 1 using 2 median 2 median 3 splits 3 splits 4 of 3 splits 6 time 4 of 5 sleeping 6 time 7 at 6 time 36 and 6 time 40 cl 7 at 11 years 8 1.5 9 and 9 and 10 2 9 and 11 years 11 years 12 we 11 years 19 short 11 years 21 cs 12 we 13 defined 13 defined 14 sleep 14 sleep 15 duration 14 sleep 19 short 15 duration 17 : 17 : 19 short 18 consistently 19 short 20 ( 21 cs 21 cs 24 = 21 cs 27 , 22 , 24 = 23 n 24 = 24 = 25 122 24 = 26 ) 28 inconsistent 33 = 28 inconsistent 36 and 30 i 33 = 31 , 33 = 32 n 33 = 33 = 34 143 33 = 35 ) 36 and 38 long 37 consistently 38 long 40 cl 43 = 41 , 43 = 42 n 43 = 43 = 44 216 43 = 45 ) results : compared to cl - children , cs - sleepers differed in their fmi development with respect to linear , quadratic and cubic trend ( [all] p < 0.04 ) , resulting in progressively higher fmi levels until age 7 independently of early life or socioeconomic factors . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 49 . 2 : 11 sleepers 2 : 12 differed 2 : 32 , 3 compared 4 to 3 compared 10 - 3 compared 11 sleepers 4 to 5 cl 5 cl 7 children 5 cl 9 cs 6 - 7 children 7 children 8 , 8 , 9 cs 9 cs 10 - 11 sleepers 12 differed 12 differed 13 in 12 differed 19 to 13 in 16 development 14 their 16 development 15 fmi 16 development 16 development 17 with 17 with 18 respect 19 to 23 and 20 linear 21 , 21 , 22 quadratic 21 , 23 and 23 and 25 trend 23 and 29 < 24 cubic 25 trend 26 ( 29 < 28 p 29 < 29 < 30 0.04 29 < 31 ) 32 , 33 resulting 32 , 38 levels 33 resulting 34 in 33 resulting 38 levels 34 in 37 fmi 35 progressively 36 higher 36 higher 37 fmi 38 levels 39 until 38 levels 42 independently 39 until 40 age 40 age 41 7 42 independently 43 of 43 of 46 or 44 early 45 life 45 life 46 or 46 or 48 factors 47 socioeconomic 48 factors trajectories of bmi and ffmi did not differ between the sleep duration categories . 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 8 differ 0 ###LEFT-WALL### 14 . 1 trajectories 2 of 1 trajectories 4 and 2 of 3 bmi 4 and 5 ffmi 4 and 6 did 6 did 7 not 6 did 8 differ 8 differ 9 between 9 between 13 categories 10 the 13 categories 11 sleep 13 categories 12 duration 13 categories conclusion : consistently short sleep duration in the critical window of early childhood appears to exert a moderate but sustained adverse effect on the development of fat [mass] - but not fat free mass - until age 7 . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 6 duration 2 : 19 but 3 consistently 6 duration 4 short 6 duration 5 sleep 6 duration 6 duration 7 in 6 duration 11 of 6 duration 19 but 7 in 10 window 8 the 10 window 9 critical 10 window 11 of 13 childhood 12 early 13 childhood 14 appears 15 to 14 appears 16 exert 14 appears 19 but 15 to 16 exert 16 exert 18 moderate 17 a 18 moderate 19 but 20 sustained 20 sustained 30 but 20 sustained 36 until 21 adverse 22 effect 22 effect 23 on 22 effect 30 but 23 on 25 development 24 the 25 development 25 development 26 of 26 of 27 fat 29 - 30 but 30 but 31 not 30 but 34 mass 31 not 32 fat 32 fat 34 mass 33 free 34 mass 35 - 36 until 36 until 37 age 36 until 39 . 37 age 38 7 memory training has often been supported as a potential means to improve performance for older adults . 0 ###LEFT-WALL### 2 training 0 ###LEFT-WALL### 12 improve 0 ###LEFT-WALL### 17 . 1 memory 2 training 2 training 3 has 3 has 5 been 4 often 5 been 5 been 6 supported 6 supported 7 as 6 supported 11 to 7 as 10 means 8 a 9 potential 8 a 10 means 9 potential 10 means 11 to 12 improve 12 improve 13 performance 13 performance 14 for 14 for 16 adults 15 older 16 adults less often studied are the characteristics of trainees that benefit most from training . 0 ###LEFT-WALL### 3 studied 0 ###LEFT-WALL### 4 are 0 ###LEFT-WALL### 14 . 1 less 2 often 2 often 3 studied 3 studied 4 are 4 are 6 characteristics 5 the 6 characteristics 6 characteristics 7 of 7 of 8 trainees 8 trainees 9 that 8 trainees 10 benefit 9 that 10 benefit 10 benefit 11 most 11 most 12 from 12 from 13 training using a self - regulatory perspective , the current project examined a latent growth curve model to predict training - related gains for middle - aged and older adult trainees from individual differences ( e.g [.] , education ) , information processing skills ( strategy use [ )(and self - regulatory factors such as self - efficacy , control , and active engagement in training . 1 using 3 self 1 using 7 , 1 using 10 project 2 a 3 self 3 self 6 perspective 4 - 6 perspective 5 regulatory 6 perspective 6 perspective 7 , 8 the 10 project 9 current 10 project 10 project 11 examined 11 examined 16 model 11 examined 17 to 12 a 16 model 13 latent 14 growth 14 growth 15 curve 15 curve 16 model 17 to 18 predict 18 predict 27 and 18 predict 30 trainees 19 training 26 aged 19 training 27 and 20 - 21 related 21 related 22 gains 21 related 23 for 21 related 25 - 21 related 26 aged 23 for 24 middle 27 and 28 older 29 adult 30 trainees 30 trainees 31 from 30 trainees 42 processing 31 from 41 information 32 individual 38 education 32 individual 40 , 32 individual 41 information 33 differences 35 e.g 34 ( 35 e.g 35 e.g 37 , 37 , 38 education 38 education 39 ) 42 processing 43 skills 42 processing 50 - 42 processing 54 as 44 ( 50 - 45 strategy 46 use 46 use 48 )(and 48 )(and 49 self 48 )(and 50 - 50 - 52 factors 51 regulatory 52 factors 53 such 54 as 54 as 55 self 55 self 61 and 56 - 61 and 57 efficacy 58 , 58 , 59 control 58 , 61 and 60 , 61 and 61 and 63 engagement 61 and 66 . 62 active 63 engagement 63 engagement 64 in 64 in 65 training the best fit to the text recall data was a model focusing on self [-] efficacy change as the main predictor of memory change , and that model showed significantly better fit than a model also including strategy usage variables as predictors . 0 ###LEFT-WALL### 2 best 0 ###LEFT-WALL### 3 fit 0 ###LEFT-WALL### 43 . 1 the 2 best 2 best 3 fit 3 fit 4 to 3 fit 13 on 3 fit 18 as 3 fit 33 than 4 to 7 recall 5 the 7 recall 6 text 7 recall 7 recall 8 data 7 recall 12 focusing 8 data 9 was 9 was 11 model 10 a 11 model 11 model 12 focusing 13 on 17 change 14 self 16 efficacy 16 efficacy 17 change 18 as 21 predictor 19 the 21 predictor 20 main 21 predictor 21 predictor 22 of 22 of 23 memory 23 memory 26 and 23 memory 32 fit 24 change 26 and 25 , 26 and 26 and 28 model 26 and 29 showed 27 that 28 model 29 showed 31 better 29 showed 32 fit 30 significantly 31 better 33 than 35 model 34 a 35 model 35 model 37 including 36 also 37 including 37 including 40 variables 38 strategy 39 usage 39 usage 40 variables 40 variables 41 as 41 as 42 predictors in these models , overall performance was significantly predicted by age and memory self - efficacy , and subsequent training - related gains in performance were best predicted directly by change in self [-] efficacy ( text recall ) , or indirectly through the impact of active engagement and self - efficacy on gains ( name recall ) . 0 ###LEFT-WALL### 6 performance 0 ###LEFT-WALL### 9 predicted 0 ###LEFT-WALL### 28 predicted 0 ###LEFT-WALL### 59 . 1 in 3 models 1 in 4 , 1 in 6 performance 2 these 3 models 4 , 5 overall 5 overall 6 performance 6 performance 7 was 7 was 9 predicted 8 significantly 9 predicted 9 predicted 10 by 10 by 12 and 11 age 12 and 12 and 14 self 13 memory 14 self 15 - 28 predicted 16 efficacy 18 and 17 , 18 and 18 and 20 training 18 and 21 - 18 and 23 gains 18 and 26 were 18 and 28 predicted 19 subsequent 20 training 22 related 23 gains 23 gains 24 in 23 gains 26 were 24 in 25 performance 27 best 28 predicted 28 predicted 29 directly 28 predicted 30 by 28 predicted 53 on 28 predicted 58 ) 30 by 41 or 31 change 32 in 31 change 41 or 32 in 35 efficacy 33 self 35 efficacy 35 efficacy 38 recall 36 ( 38 recall 37 text 38 recall 38 recall 39 ) 40 , 41 or 41 or 52 efficacy 42 indirectly 43 through 43 through 52 efficacy 44 the 45 impact 45 impact 46 of 45 impact 49 and 46 of 48 engagement 47 active 48 engagement 49 and 50 self 49 and 51 - 49 and 52 efficacy 53 on 54 gains 54 gains 57 recall 55 ( 57 recall 56 name 57 recall 57 recall 58 ) these results underscore the benefits of targeting self [-] regulatory factors in intervention programs designed to improve memory skills . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 underscore 0 ###LEFT-WALL### 20 . 1 these 2 results 2 results 3 underscore 3 underscore 5 benefits 3 underscore 12 in 4 the 5 benefits 5 benefits 6 of 6 of 7 targeting 7 targeting 11 factors 8 self 11 factors 10 regulatory 11 factors 12 in 14 programs 13 intervention 14 programs 14 programs 15 designed 15 designed 16 to 16 to 17 improve 17 improve 19 skills 18 memory 19 skills the burden of providing informal care to a family member can lead to caregiver depression and potentially harmful caregiving behavior . 0 ###LEFT-WALL### 2 burden 0 ###LEFT-WALL### 14 caregiver 0 ###LEFT-WALL### 21 . 1 the 2 burden 2 burden 3 of 2 burden 11 can 3 of 4 providing 4 providing 6 care 4 providing 7 to 5 informal 6 care 7 to 10 member 8 a 9 family 8 a 10 member 9 family 10 member 11 can 12 lead 12 lead 13 to 13 to 14 caregiver 14 caregiver 16 and 15 depression 16 and 16 and 17 potentially 16 and 20 behavior 18 harmful 20 behavior 19 caregiving 20 behavior given the interpersonal nature of caregiving , the relationship between caregivers and care recipients may impact caregiver responses . 0 ###LEFT-WALL### 9 relationship 0 ###LEFT-WALL### 16 impact 0 ###LEFT-WALL### 19 . 1 given 4 nature 1 given 7 , 1 given 9 relationship 2 the 4 nature 3 interpersonal 4 nature 4 nature 5 of 5 of 6 caregiving 8 the 9 relationship 9 relationship 10 between 9 relationship 15 may 10 between 12 and 11 caregivers 12 and 12 and 14 recipients 13 care 14 recipients 15 may 16 impact 16 impact 18 responses 17 caregiver 18 responses we applied attachment theory to understanding caregiver depression , and [both] potentially harmful and exemplary caregiving responses . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 applied 0 ###LEFT-WALL### 18 . 1 we 2 applied 2 applied 4 theory 2 applied 5 to 3 attachment 4 theory 5 to 6 understanding 6 understanding 10 and 7 caregiver 8 depression 8 depression 10 and 9 , 10 and 10 and 12 potentially 10 and 17 responses 13 harmful 14 and 14 and 15 exemplary 14 and 17 responses 16 caregiving 17 responses we present data from 430 caregivers in the family relationships in late life ( frill 2 ) project , a multisite , longitudinal study of caregiving . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 present 1 we 2 present 2 present 3 data 2 present 4 from 2 present 7 in 4 from 6 caregivers 5 430 6 caregivers 7 in 18 project 8 the 18 project 9 family 10 relationships 10 relationships 11 in 10 relationships 18 project 11 in 13 life 12 late 13 life 13 life 15 frill 14 ( 15 frill 15 frill 16 2 15 frill 17 ) 18 project 24 study 19 , 24 study 20 a 24 study 21 multisite 22 , 21 multisite 24 study 23 longitudinal 24 study 24 study 25 of 24 study 27 . 25 of 26 caregiving age , gender , and model [of] self were related to caregiving responses , suggesting that model [of] self may help identify caregivers at risk for poor responses . 0 ###LEFT-WALL### 5 and 0 ###LEFT-WALL### 14 , 0 ###LEFT-WALL### 29 . 1 age 2 , 2 , 3 gender 2 , 5 and 4 , 5 and 5 and 8 self 5 and 14 , 6 model 8 self 9 were 10 related 9 were 14 , 10 related 11 to 11 to 12 caregiving 12 caregiving 13 responses 14 , 21 help 14 , 24 at 15 suggesting 19 self 15 suggesting 20 may 16 that 19 self 17 model 19 self 20 may 21 help 21 help 22 identify 22 identify 23 caregivers 24 at 25 risk 25 risk 26 for 26 for 28 responses 27 poor 28 responses we examined the relationships between age , changes in the number of peripheral partners , and changes in loneliness over 2 years among 365 hong kong chinese aged 18 - 91 years . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 16 and 0 ###LEFT-WALL### 33 . 1 we 16 and 2 examined 4 relationships 2 examined 5 between 2 examined 16 and 3 the 4 relationships 5 between 6 age 6 age 8 changes 7 , 8 changes 8 changes 9 in 8 changes 12 of 8 changes 15 , 9 in 11 number 10 the 11 number 12 of 14 partners 13 peripheral 14 partners 16 and 17 changes 16 and 18 in 16 and 20 over 16 and 23 among 18 in 19 loneliness 20 over 22 years 21 2 22 years 23 among 32 years 24 365 32 years 25 hong 26 kong 26 kong 28 aged 27 chinese 28 aged 28 aged 32 years 29 18 30 - 30 - 31 91 30 - 32 years we also tested the moderating role [of] interdependent self - construal in the relationships . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 tested 1 we 3 tested 2 also 3 tested 3 tested 9 self 4 the 9 self 5 moderating 6 role 6 role 9 self 8 interdependent 9 self 9 self 11 construal 10 - 11 construal 11 construal 12 in 11 construal 15 . 12 in 14 relationships 13 the 14 relationships results showed that the well [-] documented negative association between age and number of peripheral partners over time was only significant for individuals with low and medium interdependence but not for those [with] high [interdependence] . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 showed 0 ###LEFT-WALL### 36 . 1 results 2 showed 2 showed 3 that 3 that 9 association 3 that 19 was 4 the 9 association 5 well 7 documented 7 documented 9 association 8 negative 9 association 9 association 10 between 9 association 14 of 9 association 19 was 10 between 12 and 11 age 12 and 12 and 13 number 14 of 16 partners 15 peripheral 16 partners 16 partners 17 over 17 over 18 time 19 was 20 only 19 was 21 significant 21 significant 22 for 21 significant 29 but 22 for 23 individuals 24 with 26 and 24 with 29 but 25 low 26 and 26 and 28 interdependence 27 medium 28 interdependence 29 but 30 not 29 but 31 for 31 for 34 high 32 those 34 high moreover , only older [and] middle [-] aged adults high in interdependence benefitted [from] having more peripheral social partners by showing decreased loneliness in the 2 - year interval . 0 ###LEFT-WALL### 3 only 0 ###LEFT-WALL### 22 decreased 0 ###LEFT-WALL### 27 - 1 moreover 2 , 1 moreover 3 only 3 only 9 adults 4 older 6 middle 6 middle 8 aged 8 aged 9 adults 9 adults 10 high 9 adults 20 by 9 adults 22 decreased 10 high 11 in 11 in 19 partners 12 interdependence 13 benefitted 13 benefitted 19 partners 15 having 19 partners 16 more 17 peripheral 17 peripheral 18 social 18 social 19 partners 20 by 21 showing 22 decreased 23 loneliness 22 decreased 24 in 24 in 26 2 25 the 26 2 27 - 29 interval 27 - 30 . 28 year 29 interval the isolation paradigm is the classic method for studying the effects of distinctiveness on memory ( hunt , 1995 ) . 0 ###LEFT-WALL### 3 paradigm 0 ###LEFT-WALL### 4 is 0 ###LEFT-WALL### 21 . 1 the 3 paradigm 2 isolation 3 paradigm 3 paradigm 4 is 4 is 7 method 5 the 7 method 6 classic 7 method 7 method 8 for 8 for 9 studying 9 studying 11 effects 9 studying 14 on 10 the 11 effects 11 effects 12 of 12 of 13 distinctiveness 14 on 15 memory 15 memory 17 hunt 15 memory 19 1995 16 ( 17 hunt 17 hunt 18 , 18 , 19 1995 19 1995 20 ) previous studies using the isolation paradigm with older adults ( bireta , suprenant [,] & neath , 2008 [;] cimbalo & brink , 1982 [;] geraci , mcdaniel , manzano [,] & roediger ( 2009 ) [;] vitali et al . , 2006 ) placed the isolated items late in the study list . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 45 placed 0 ###LEFT-WALL### 54 . 1 previous 2 studies 2 studies 3 using 2 studies 45 placed 3 using 6 paradigm 3 using 7 with 4 the 6 paradigm 5 isolation 6 paradigm 7 with 9 adults 7 with 40 al 8 older 9 adults 9 adults 22 brink 10 ( 22 brink 11 bireta 15 & 12 , 15 & 13 suprenant 15 & 15 & 16 neath 16 neath 21 & 17 , 21 & 18 2008 20 cimbalo 20 cimbalo 21 & 21 & 22 brink 22 brink 26 geraci 22 brink 28 mcdaniel 22 brink 36 ) 23 , 26 geraci 24 1982 26 geraci 26 geraci 27 , 27 , 28 mcdaniel 28 mcdaniel 33 roediger 28 mcdaniel 36 ) 29 , 33 roediger 30 manzano 32 & 32 & 33 roediger 33 roediger 35 2009 33 roediger 36 ) 34 ( 35 2009 35 2009 36 ) 38 vitali 40 al 39 et 40 al 40 al 41 . 40 al 43 2006 42 , 43 2006 43 2006 44 ) 45 placed 48 items 45 placed 49 late 45 placed 50 in 46 the 48 items 47 isolated 48 items 50 in 53 list 51 the 53 list 52 study 53 list the current experiments , which are the first to investigate the isolation effect in young and older adults when the isolated item occurs early in the list , were motivated by a new framework for understanding age - related differences in the beneficial effects of distinctive processing . 0 ###LEFT-WALL### 3 experiments 0 ###LEFT-WALL### 29 were 0 ###LEFT-WALL### 39 related 1 the 3 experiments 2 current 3 experiments 3 experiments 5 which 3 experiments 29 were 4 , 5 which 5 which 6 are 5 which 28 , 6 are 8 first 6 are 14 in 6 are 19 when 7 the 8 first 8 first 9 to 8 first 10 investigate 9 to 10 investigate 10 investigate 13 effect 11 the 13 effect 12 isolation 13 effect 14 in 18 adults 15 young 16 and 16 and 17 older 16 and 18 adults 19 when 22 item 19 when 23 occurs 20 the 22 item 21 isolated 22 item 22 item 23 occurs 23 occurs 24 early 23 occurs 25 in 25 in 27 list 26 the 27 list 29 were 30 motivated 30 motivated 31 by 30 motivated 35 for 31 by 34 framework 32 a 33 new 32 a 34 framework 33 new 34 framework 35 for 36 understanding 36 understanding 37 age 38 - 39 related 39 related 40 differences 39 related 41 in 39 related 48 . 41 in 44 effects 42 the 44 effects 43 beneficial 44 effects 44 effects 45 of 45 of 47 processing 46 distinctive 47 processing the framework , which is motivated by hunt ['s] ( 2006 ) discussion of distinctiveness and craik ['s] ( 1986 ) environmental support view , proposes that when contextual support is provided for the processing of both the difference and similarity components , older adults [are] more likely to show beneficial effects of distinctiveness . 0 ###LEFT-WALL### 2 framework 0 ###LEFT-WALL### 6 motivated 1 the 2 framework 2 framework 4 which 2 framework 6 motivated 3 , 4 which 4 which 5 is 6 motivated 7 by 6 motivated 16 and 7 by 8 hunt 8 hunt 11 2006 10 ( 11 2006 11 2006 12 ) 13 discussion 14 of 13 discussion 16 and 14 of 15 distinctiveness 16 and 24 view 16 and 25 , 17 craik 20 1986 17 craik 23 support 19 ( 20 1986 20 1986 21 ) 22 environmental 23 support 23 support 24 view 25 , 26 proposes 26 proposes 27 that 27 that 28 when 28 when 30 support 28 when 32 provided 29 contextual 30 support 30 support 31 is 31 is 32 provided 32 provided 33 for 33 for 35 processing 34 the 35 processing 35 processing 36 of 36 of 40 and 37 both 40 and 38 the 39 difference 39 difference 40 and 40 and 42 components 40 and 45 adults 41 similarity 42 components 43 , 45 adults 44 older 45 adults 45 adults 49 to 45 adults 50 show 45 adults 55 . 47 more 48 likely 48 likely 49 to 49 to 50 show 50 show 52 effects 51 beneficial 52 effects 52 effects 53 of 53 of 54 distinctiveness in experiment 1 , young adults showed both early and late isolation effects , while older adults showed only a late isolation effect . 0 ###LEFT-WALL### 6 adults 0 ###LEFT-WALL### 7 showed 0 ###LEFT-WALL### 14 , 0 ###LEFT-WALL### 24 . 1 in 2 experiment 1 in 4 , 1 in 6 adults 2 experiment 3 1 5 young 6 adults 6 adults 7 showed 7 showed 8 both 7 showed 13 effects 9 early 10 and 10 and 11 late 10 and 13 effects 12 isolation 13 effects 14 , 17 adults 14 , 18 showed 15 while 16 older 15 while 17 adults 17 adults 18 showed 18 showed 19 only 18 showed 23 effect 20 a 21 late 20 a 23 effect 21 late 22 isolation 22 isolation 23 effect in the first experiment the isolated item was the word " table " in a list of fish names . 0 ###LEFT-WALL### 7 item 0 ###LEFT-WALL### 8 was 0 ###LEFT-WALL### 20 . 1 in 4 experiment 1 in 7 item 2 the 3 first 2 the 4 experiment 5 the 7 item 6 isolated 7 item 7 item 8 was 8 was 12 table 9 the 12 table 10 word 11 " 10 word 12 table 12 table 13 " 12 table 14 in 14 in 16 list 15 a 16 list 16 list 17 of 17 of 19 names 18 fish 19 names in experiment 2 , the contrast between the isolated item and background items was increased by isolating numbers in a list of words . 0 ###LEFT-WALL### 6 contrast 0 ###LEFT-WALL### 15 increased 0 ###LEFT-WALL### 24 . 1 in 2 experiment 1 in 4 , 1 in 6 contrast 2 experiment 3 2 5 the 6 contrast 6 contrast 7 between 6 contrast 14 was 7 between 11 and 8 the 10 item 9 isolated 10 item 10 item 11 and 11 and 13 items 12 background 13 items 14 was 15 increased 15 increased 16 by 16 by 17 isolating 17 isolating 18 numbers 17 isolating 19 in 19 in 21 list 20 a 21 list 21 list 22 of 22 of 23 words in the second experiment older adults , as well as young adults , showed an early isolation effect . 0 ###LEFT-WALL### 6 adults 0 ###LEFT-WALL### 14 showed 0 ###LEFT-WALL### 19 . 1 in 4 experiment 1 in 6 adults 2 the 3 second 2 the 4 experiment 5 older 6 adults 6 adults 10 as 6 adults 14 showed 7 , 10 as 8 as 9 well 9 well 10 as 10 as 12 adults 10 as 13 , 11 young 12 adults 14 showed 18 effect 15 an 16 early 15 an 18 effect 16 early 17 isolation 17 isolation 18 effect effective social functioning is reflected in the ability to accurately characterize other people and then use this information in the service of social goals . 0 ###LEFT-WALL### 3 functioning 0 ###LEFT-WALL### 14 and 0 ###LEFT-WALL### 25 . 1 effective 3 functioning 2 social 3 functioning 3 functioning 4 is 4 is 14 and 5 reflected 6 in 5 reflected 14 and 6 in 8 ability 7 the 8 ability 8 ability 9 to 8 ability 11 characterize 9 to 11 characterize 10 accurately 11 characterize 11 characterize 13 people 12 other 13 people 14 and 16 use 15 then 16 use 16 use 18 information 16 use 19 in 17 this 18 information 19 in 21 service 20 the 21 service 21 service 22 of 22 of 24 goals 23 social 24 goals to examine this type of social functioning , the authors conducted two studies that investigated potential influences of social experience and chronic socioemotional goals on adults ' social judgments in an impression formation task . 0 ###LEFT-WALL### 10 authors 0 ###LEFT-WALL### 11 conducted 0 ###LEFT-WALL### 21 and 0 ###LEFT-WALL### 35 . 1 to 2 examine 1 to 8 , 1 to 10 authors 2 examine 5 of 3 this 5 of 4 type 5 of 5 of 6 social 5 of 7 functioning 9 the 10 authors 10 authors 11 conducted 11 conducted 13 studies 12 two 13 studies 13 studies 14 that 13 studies 15 investigated 14 that 15 investigated 15 investigated 17 influences 16 potential 17 influences 17 influences 18 of 18 of 20 experience 19 social 20 experience 21 and 24 goals 21 and 34 task 22 chronic 24 goals 23 socioemotional 24 goals 24 goals 25 on 24 goals 30 in 24 goals 34 task 25 on 29 judgments 26 adults 27 ' 27 ' 29 judgments 28 social 29 judgments 30 in 33 formation 31 an 33 formation 32 impression 33 formation [in] line with a social expertise framework , middle - aged and older adults were more sensitive [to] [trait] - diagnostic behavioral information than were younger adults . 0 ###LEFT-WALL### 8 , 0 ###LEFT-WALL### 10 - 0 ###LEFT-WALL### 28 . 2 line 3 with 2 line 8 , 3 with 7 framework 4 a 7 framework 5 social 6 expertise 6 expertise 7 framework 8 , 9 middle 10 - 14 adults 10 - 15 were 10 - 20 - 11 aged 12 and 12 and 13 older 12 and 14 adults 14 adults 15 were 15 were 17 sensitive 16 more 17 sensitive 20 - 23 information 20 - 25 were 21 diagnostic 23 information 22 behavioral 23 information 23 information 25 were 24 than 25 were 25 were 27 adults 26 younger 27 adults relative to younger adults , older adults paid more attention to negative than to positive information when it related to morality traits . 0 ###LEFT-WALL### 7 adults 0 ###LEFT-WALL### 8 paid 0 ###LEFT-WALL### 23 . 1 relative 2 to 1 relative 5 , 1 relative 7 adults 2 to 4 adults 3 younger 4 adults 6 older 7 adults 7 adults 8 paid 8 paid 10 attention 8 paid 13 than 9 more 10 attention 10 attention 11 to 10 attention 12 negative 11 to 12 negative 13 than 14 to 14 to 16 information 15 positive 16 information 16 information 17 when 17 when 18 it 17 when 19 related 18 it 19 related 19 related 20 to 20 to 22 traits 21 morality 22 traits increasing the salience of the social context , and presumably activating socioemotional goals , did not alter this pattern of performance . 0 ###LEFT-WALL### 1 increasing 0 ###LEFT-WALL### 17 alter 0 ###LEFT-WALL### 22 . 1 increasing 9 and 1 increasing 15 did 2 the 3 salience 3 salience 4 of 3 salience 9 and 4 of 7 context 5 the 7 context 6 social 7 context 8 , 9 and 9 and 10 presumably 9 and 13 goals 9 and 14 , 11 activating 13 goals 12 socioemotional 13 goals 15 did 16 not 15 did 17 alter 17 alter 19 pattern 18 this 19 pattern 19 pattern 20 of 20 of 21 performance consistent with a heightened focus on socioemotional goals , older adults ' judgments were more consistently influenced by their attributions of traits that would likely impact the affective outcomes associated with interpersonal interactions . 0 ###LEFT-WALL### 13 judgments 0 ###LEFT-WALL### 17 influenced 0 ###LEFT-WALL### 34 . 1 consistent 2 with 1 consistent 6 on 1 consistent 9 , 1 consistent 13 judgments 2 with 5 focus 3 a 5 focus 4 heightened 5 focus 6 on 8 goals 7 socioemotional 8 goals 10 older 11 adults 11 adults 12 ' 12 ' 13 judgments 13 judgments 14 were 14 were 17 influenced 15 more 16 consistently 16 consistently 17 influenced 17 influenced 18 by 17 influenced 31 with 18 by 20 attributions 19 their 20 attributions 20 attributions 21 of 21 of 22 traits 22 traits 23 that 22 traits 24 would 23 that 24 would 24 would 26 impact 25 likely 26 impact 26 impact 29 outcomes 27 the 29 outcomes 28 affective 29 outcomes 29 outcomes 30 associated 31 with 33 interactions 32 interpersonal 33 interactions the results demonstrate the interaction between social knowledge , situational social goals , and chronic socioemotional goals in determining age differences in social information processing . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 demonstrate 0 ###LEFT-WALL### 9 , 0 ###LEFT-WALL### 26 . 1 the 2 results 2 results 3 demonstrate 3 demonstrate 5 interaction 4 the 5 interaction 5 interaction 6 between 6 between 8 knowledge 7 social 8 knowledge 9 , 14 and 10 situational 12 goals 11 social 12 goals 12 goals 14 and 13 , 14 and 14 and 17 goals 14 and 18 in 15 chronic 17 goals 16 socioemotional 17 goals 18 in 19 determining 19 determining 21 differences 20 age 21 differences 21 differences 22 in 22 in 25 processing 23 social 25 processing 24 information 25 processing inhibitory control functions in old age were investigated with the " masked prime " paradigm in which participants executed speeded manual choice responses to simple visual targets . 0 ###LEFT-WALL### 1 inhibitory 0 ###LEFT-WALL### 8 investigated 0 ###LEFT-WALL### 28 . 1 inhibitory 3 functions 1 inhibitory 7 were 1 inhibitory 8 investigated 2 control 3 functions 3 functions 4 in 3 functions 7 were 4 in 6 age 5 old 6 age 8 investigated 9 with 8 investigated 24 to 9 with 15 paradigm 10 the 11 " 10 the 15 paradigm 12 masked 15 paradigm 13 prime 14 " 13 prime 15 paradigm 15 paradigm 16 in 16 in 17 which 16 in 18 participants 16 in 20 speeded 18 participants 19 executed 18 participants 20 speeded 20 speeded 23 responses 21 manual 23 responses 22 choice 23 responses 24 to 27 targets 25 simple 27 targets 26 visual 27 targets these were preceded -- [either] immediately [or] at some earlier time -- by a [backward] [-] masked prime . 0 ###LEFT-WALL### 1 these 0 ###LEFT-WALL### 3 preceded 0 ###LEFT-WALL### 19 . 1 these 2 were 2 were 3 preceded 3 preceded 8 at 3 preceded 13 by 4 -- 6 immediately 4 -- 8 at 8 at 11 time 8 at 12 -- 9 some 11 time 10 earlier 11 time 13 by 18 prime 14 a 18 prime 17 masked 18 prime young adults produced positive compatibility effects ( pces ) -- faster and more accurate responses for matching than for nonmatching prime - target pairs -- when prime and target immediately followed each other , and the reverse effect ( negative compatibility effect , nce ) for targets that followed the prime after a short interval . 0 ###LEFT-WALL### 2 adults 0 ###LEFT-WALL### 3 produced 0 ###LEFT-WALL### 10 -- 1 young 2 adults 2 adults 3 produced 3 produced 6 effects 4 positive 5 compatibility 5 compatibility 6 effects 6 effects 8 pces 7 ( 8 pces 8 pces 9 ) 10 -- 35 and 10 -- 43 , 10 -- 56 . 11 faster 12 and 12 and 13 more 12 and 15 responses 14 accurate 15 responses 15 responses 16 for 15 responses 35 and 16 for 17 matching 17 matching 18 than 18 than 19 for 19 for 20 nonmatching 20 nonmatching 24 pairs 20 nonmatching 26 when 21 prime 22 - 21 prime 23 target 23 target 24 pairs 25 -- 26 when 26 when 28 and 26 when 31 followed 26 when 34 , 27 prime 28 and 28 and 29 target 28 and 31 followed 30 immediately 31 followed 31 followed 33 other 32 each 33 other 35 and 38 effect 35 and 42 effect 36 the 38 effect 37 reverse 38 effect 39 ( 42 effect 40 negative 42 effect 41 compatibility 42 effect 42 effect 43 , 43 , 48 that 43 , 49 followed 44 nce 45 ) 44 nce 48 that 46 for 47 targets 46 for 48 that 48 that 49 followed 49 followed 51 prime 49 followed 52 after 50 the 51 prime 52 after 55 interval 53 a 55 interval 54 short 55 interval older adults produced similar pces to young adults , indicating intact low - level motor activation , but failed to produce normal nces even with longer delays ( experiment 1 ) , increased opportunity for prime processing ( experiment 2 ) , and prolonged learning ( experiment 3 ) . 0 ###LEFT-WALL### 2 adults 0 ###LEFT-WALL### 43 and 0 ###LEFT-WALL### 50 . 1 older 2 adults 2 adults 43 and 3 produced 5 pces 3 produced 6 to 3 produced 10 indicating 3 produced 43 and 4 similar 5 pces 6 to 8 adults 7 young 8 adults 9 , 10 indicating 10 indicating 16 activation 10 indicating 42 , 11 intact 14 level 12 low 13 - 12 low 14 level 14 level 15 motor 15 motor 16 activation 16 activation 18 but 17 , 18 but 18 but 32 , 18 but 42 , 19 failed 20 to 19 failed 32 , 20 to 21 produce 21 produce 23 nces 21 produce 24 even 22 normal 23 nces 24 even 25 with 25 with 27 delays 26 longer 27 delays 27 delays 29 experiment 28 ( 29 experiment 29 experiment 30 1 29 experiment 31 ) 32 , 33 increased 33 increased 34 opportunity 34 opportunity 35 for 34 opportunity 39 experiment 35 for 37 processing 36 prime 37 processing 38 ( 39 experiment 39 experiment 40 2 39 experiment 41 ) 43 and 44 prolonged 44 prolonged 45 learning 45 learning 47 experiment 46 ( 47 experiment 47 experiment 48 3 47 experiment 49 ) however , a fine - grained analysis of each individual 's time course of masked priming effects revealed nces in the majority of older adults , of the same magnitude as those of young adults . 0 ###LEFT-WALL### 7 analysis 0 ###LEFT-WALL### 18 revealed 1 however 2 , 1 however 7 analysis 3 a 4 fine 3 a 7 analysis 4 fine 5 - 4 fine 7 analysis 6 grained 7 analysis 7 analysis 8 of 7 analysis 18 revealed 8 of 13 course 9 each 10 individual 10 individual 11 's 11 's 13 course 12 time 13 course 13 course 14 of 14 of 17 effects 15 masked 16 priming 16 priming 17 effects 18 revealed 19 nces 18 revealed 20 in 20 in 25 adults 21 the 22 majority 22 majority 23 of 22 majority 25 adults 23 of 25 adults 24 older 25 adults 25 adults 27 of 26 , 27 of 27 of 30 magnitude 27 of 36 . 28 the 29 same 29 same 30 magnitude 30 magnitude 31 as 30 magnitude 33 of 31 as 32 those 33 of 35 adults 34 young 35 adults these were significantly delayed ( even more than expected on the basis of general slowing ) , indicating [a] disproportionate impairment of low - level inhibitory motor control in old age . 0 ###LEFT-WALL### 1 these 0 ###LEFT-WALL### 4 delayed 1 these 2 were 2 were 4 delayed 3 significantly 4 delayed 4 delayed 9 expected 4 delayed 18 indicating 5 ( 7 more 5 ( 9 expected 6 even 7 more 8 than 9 expected 9 expected 10 on 9 expected 16 ) 10 on 12 basis 11 the 12 basis 12 basis 13 of 13 of 14 general 14 general 15 slowing 17 , 18 indicating 18 indicating 21 impairment 18 indicating 29 in 18 indicating 32 . 20 disproportionate 21 impairment 21 impairment 22 of 22 of 28 control 23 low 24 - 23 low 25 level 25 level 28 control 26 inhibitory 27 motor 27 motor 28 control 29 in 31 age 30 old 31 age one possible explanation for the individual differences in outcomes of stress is the diversity of inputs that produce perceptions of being stressed . 0 ###LEFT-WALL### 3 explanation 0 ###LEFT-WALL### 22 stressed 0 ###LEFT-WALL### 23 . 1 one 3 explanation 2 possible 3 explanation 3 explanation 4 for 3 explanation 8 in 3 explanation 10 of 3 explanation 12 is 4 for 7 differences 5 the 7 differences 6 individual 7 differences 8 in 9 outcomes 10 of 11 stress 12 is 14 diversity 13 the 14 diversity 14 diversity 15 of 14 diversity 20 of 15 of 16 inputs 16 inputs 17 that 16 inputs 18 produce 17 that 18 produce 18 produce 19 perceptions 20 of 21 being 21 being 22 stressed the current study examines how combinations of contextual features ( e.g [.] , social isolation , neighborhood quality , health problems , age discrimination , financial concerns , and recent life events ) of later life contribute to overall feelings of stress . 0 ###LEFT-WALL### 3 study 0 ###LEFT-WALL### 4 examines 0 ###LEFT-WALL### 43 . 1 the 3 study 2 current 3 study 3 study 4 examines 4 examines 5 how 5 how 29 and 5 how 37 contribute 6 combinations 7 of 6 combinations 29 and 7 of 9 features 8 contextual 9 features 9 features 15 isolation 10 ( 15 isolation 11 e.g 13 , 11 e.g 15 isolation 14 social 15 isolation 15 isolation 18 quality 15 isolation 24 discrimination 15 isolation 28 , 16 , 18 quality 17 neighborhood 18 quality 18 quality 21 problems 18 quality 22 , 19 , 21 problems 20 health 21 problems 21 problems 22 , 22 , 24 discrimination 23 age 24 discrimination 24 discrimination 27 concerns 24 discrimination 28 , 25 , 27 concerns 26 financial 27 concerns 27 concerns 28 , 28 , 29 and 29 and 32 events 29 and 33 ) 29 and 34 of 29 and 37 contribute 30 recent 31 life 31 life 32 events 34 of 36 life 35 later 36 life 37 contribute 38 to 38 to 40 feelings 39 overall 40 feelings 40 feelings 41 of 41 of 42 stress recursive partitioning techniques ( regression trees and random forests ) were used to examine unique interrelations between predictors of perceived stress in a sample of 282 community [-] dwelling adults . 0 ###LEFT-WALL### 1 recursive 0 ###LEFT-WALL### 12 used 0 ###LEFT-WALL### 31 . 1 recursive 2 partitioning 1 recursive 11 were 2 partitioning 3 techniques 3 techniques 7 and 4 ( 7 and 5 regression 6 trees 6 trees 7 and 7 and 9 forests 7 and 10 ) 8 random 9 forests 11 were 12 used 12 used 13 to 12 used 14 examine 13 to 14 examine 14 examine 16 interrelations 14 examine 17 between 14 examine 22 in 15 unique 16 interrelations 17 between 18 predictors 18 predictors 19 of 19 of 21 stress 20 perceived 21 stress 22 in 24 sample 23 a 24 sample 24 sample 25 of 25 of 30 adults 26 282 30 adults 27 community 29 dwelling 29 dwelling 30 adults random forest analyses aggregated across many trees based on permuted versions of the data and predictors ; loneliness , financial strain , neighborhood strain , ageism , and to some extent life events emerged as important predictors . 0 ###LEFT-WALL### 15 and 0 ###LEFT-WALL### 17 ; 0 ###LEFT-WALL### 38 . 1 random 2 forest 2 forest 3 analyses 3 analyses 4 aggregated 3 analyses 8 based 3 analyses 15 and 4 aggregated 5 across 5 across 7 trees 6 many 7 trees 8 based 9 on 9 on 11 versions 10 permuted 11 versions 11 versions 12 of 12 of 14 data 13 the 14 data 15 and 16 predictors 17 ; 18 loneliness 17 ; 19 , 19 , 21 strain 19 , 22 , 20 financial 21 strain 22 , 24 strain 22 , 25 , 23 neighborhood 24 strain 25 , 26 ageism 25 , 28 and 27 , 28 and 28 and 33 events 28 and 34 emerged 29 to 32 life 29 to 33 events 30 some 32 life 31 extent 32 life 33 events 34 emerged 34 emerged 35 as 35 as 37 predictors 36 important 37 predictors interviews with a subsample [of] participants provided both thick description of the complex relationships identified in the trees , as well as additional risks not appearing in the survey results . 0 ###LEFT-WALL### 1 interviews 0 ###LEFT-WALL### 30 results 0 ###LEFT-WALL### 31 . 1 interviews 2 with 1 interviews 30 results 2 with 10 description 3 a 4 subsample 3 a 10 description 4 subsample 6 participants 6 participants 7 provided 7 provided 8 both 9 thick 10 description 10 description 11 of 11 of 14 relationships 12 the 14 relationships 13 complex 14 relationships 14 relationships 15 identified 14 relationships 22 as 15 identified 16 in 15 identified 19 , 15 identified 21 well 16 in 18 trees 17 the 18 trees 20 as 21 well 22 as 24 risks 23 additional 24 risks 24 risks 25 not 25 not 26 appearing 26 appearing 27 in 27 in 29 survey 28 the 29 survey together , the analyses highlight what may be missed when stress is used as a simple unidimensional construct and can guide differential intervention efforts . 0 ###LEFT-WALL### 4 analyses 0 ###LEFT-WALL### 19 and 0 ###LEFT-WALL### 25 . 1 together 2 , 1 together 4 analyses 3 the 4 analyses 4 analyses 19 and 5 highlight 6 what 5 highlight 19 and 6 what 7 may 7 may 8 be 8 be 9 missed 9 missed 10 when 10 when 11 stress 10 when 13 used 11 stress 12 is 12 is 13 used 13 used 14 as 14 as 18 construct 15 a 16 simple 15 a 18 construct 16 simple 18 construct 17 unidimensional 18 construct 19 and 20 can 19 and 24 efforts 20 can 21 guide 21 guide 23 intervention 22 differential 23 intervention lothian birth cohorts , 1936 and 1921 were used to study the longitudinal comparability of five - factor model ( mccrae & john , 1992 ) personality traits from ages 69 to 72 years and from ages 81 to 87 years , and cross - cohort comparability between ages 69 and 81 years . 0 ###LEFT-WALL### 3 cohorts 0 ###LEFT-WALL### 4 , 1 lothian 2 birth 2 birth 3 cohorts 4 , 6 and 4 , 9 used 5 1936 6 and 6 and 7 1921 6 and 8 were 8 were 9 used 9 used 10 to 9 used 11 study 10 to 11 study 11 study 14 comparability 11 study 29 from 12 the 14 comparability 13 longitudinal 14 comparability 14 comparability 15 of 15 of 28 traits 16 five 23 john 16 five 27 personality 17 - 23 john 18 factor 19 model 19 model 22 & 20 ( 22 & 21 mccrae 22 & 22 & 23 john 23 john 25 1992 23 john 26 ) 24 , 25 1992 25 1992 26 ) 27 personality 28 traits 29 from 43 and 30 ages 31 69 30 ages 35 and 30 ages 43 and 32 to 34 years 32 to 35 and 33 72 34 years 35 and 36 from 36 from 37 ages 37 ages 38 81 37 ages 39 to 39 to 41 years 40 87 41 years 42 , 43 and 43 and 44 cross 43 and 51 and 45 - 51 and 46 cohort 47 comparability 47 comparability 48 between 47 comparability 51 and 48 between 49 ages 49 ages 50 69 51 and 53 years 51 and 54 . 52 81 53 years personality was measured using the 50 - item international personality item pool ( goldberg , 1999 ) . 0 ###LEFT-WALL### 1 personality 0 ###LEFT-WALL### 2 was 0 ###LEFT-WALL### 18 . 1 personality 2 was 2 was 3 measured 3 measured 4 using 4 using 6 50 5 the 6 50 6 50 12 pool 7 - 12 pool 8 item 12 pool 9 international 10 personality 10 personality 11 item 11 item 12 pool 12 pool 14 goldberg 12 pool 16 1999 12 pool 17 ) 13 ( 14 goldberg 14 goldberg 15 , 15 , 16 1999 16 1999 17 ) satisfactory measurement invariance was established across time and cohorts . 0 ###LEFT-WALL### 3 invariance 0 ###LEFT-WALL### 5 established 0 ###LEFT-WALL### 10 . 1 satisfactory 2 measurement 2 measurement 3 invariance 3 invariance 4 was 4 was 5 established 5 established 6 across 6 across 8 and 7 time 8 and 8 and 9 cohorts high rank - order stability was observed in both cohorts . 0 ###LEFT-WALL### 5 stability 0 ###LEFT-WALL### 7 observed 0 ###LEFT-WALL### 11 . 1 high 4 order 2 rank 3 - 2 rank 4 order 4 order 5 stability 5 stability 6 was 6 was 7 observed 7 observed 8 in 8 in 10 cohorts 9 both 10 cohorts almost no mean - level change was observed in the younger cohort , whereas extraversion , agreeableness , conscientiousness , and intellect declined significantly in the older cohort . 0 ###LEFT-WALL### 6 change 0 ###LEFT-WALL### 23 declined 0 ###LEFT-WALL### 29 . 1 almost 2 no 2 no 6 change 3 mean 4 - 3 mean 6 change 5 level 6 change 6 change 7 was 7 was 8 observed 8 observed 9 in 8 observed 14 whereas 9 in 12 cohort 10 the 12 cohort 11 younger 12 cohort 13 , 14 whereas 14 whereas 21 and 15 extraversion 16 , 16 , 17 agreeableness 16 , 18 , 18 , 19 conscientiousness 18 , 21 and 20 , 21 and 21 and 22 intellect 21 and 23 declined 23 declined 24 significantly 23 declined 25 in 25 in 28 cohort 26 the 28 cohort 27 older 28 cohort the older cohort scored higher on agreeableness and conscientiousness . 0 ###LEFT-WALL### 3 cohort 0 ###LEFT-WALL### 4 scored 0 ###LEFT-WALL### 10 . 1 the 3 cohort 2 older 3 cohort 3 cohort 4 scored 4 scored 5 higher 5 higher 6 on 6 on 8 and 7 agreeableness 8 and 8 and 9 conscientiousness in these cohorts , individual differences in personality traits continued to be stable even in very old age , mean - level changes accelerated . 0 ###LEFT-WALL### 6 differences 0 ###LEFT-WALL### 10 continued 0 ###LEFT-WALL### 19 , 0 ###LEFT-WALL### 25 . 1 in 3 cohorts 1 in 4 , 1 in 6 differences 2 these 3 cohorts 5 individual 6 differences 6 differences 7 in 6 differences 10 continued 7 in 9 traits 8 personality 9 traits 10 continued 11 to 10 continued 14 even 11 to 12 be 12 be 13 stable 14 even 15 in 15 in 18 age 16 very 17 old 17 old 18 age 19 , 23 changes 19 , 24 accelerated 20 mean 21 - 20 mean 23 changes 22 level 23 changes 23 changes 24 accelerated objective : conscientious individuals tend to experience a number of health benefits [,] [not] the least of which being greater longevity . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 22 . 2 : 3 conscientious 3 conscientious 4 individuals 3 conscientious 5 tend 3 conscientious 19 being 4 individuals 5 tend 5 tend 6 to 5 tend 7 experience 6 to 7 experience 7 experience 12 benefits 7 experience 16 least 8 a 9 number 9 number 10 of 9 number 12 benefits 10 of 12 benefits 11 health 12 benefits 15 the 16 least 16 least 17 of 17 of 18 which 19 being 21 longevity 20 greater 21 longevity however , it remains an open question as to why this link with longevity occurs . 0 ###LEFT-WALL### 3 it 0 ###LEFT-WALL### 4 remains 0 ###LEFT-WALL### 16 . 1 however 2 , 1 however 3 it 3 it 4 remains 4 remains 7 question 4 remains 9 to 5 an 6 open 5 an 7 question 6 open 7 question 8 as 9 to 9 to 10 why 10 why 12 link 10 why 15 occurs 11 this 12 link 12 link 13 with 12 link 15 occurs 13 with 14 longevity the current study tested two possible mediators ( physical health and cognitive functioning ) of the link between conscientiousness and longevity . 0 ###LEFT-WALL### 3 study 0 ###LEFT-WALL### 4 tested 1 the 3 study 2 current 3 study 3 study 4 tested 4 tested 7 mediators 5 two 7 mediators 6 possible 7 mediators 7 mediators 11 and 8 ( 11 and 9 physical 10 health 10 health 11 and 11 and 13 functioning 11 and 14 ) 11 and 15 of 11 and 22 . 12 cognitive 13 functioning 15 of 17 link 16 the 17 link 17 link 18 between 18 between 20 and 19 conscientiousness 20 and 20 and 21 longevity method : we tested these mediators using a 10 [-] year longitudinal sample ( n = 512 ) , a subset of the long - running health and retirement study of aging adults . 0 ###LEFT-WALL### 1 method 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 34 . 2 : 3 we 2 : 4 tested 2 : 19 , 3 we 4 tested 4 tested 6 mediators 4 tested 7 using 5 these 6 mediators 7 using 13 sample 8 a 13 sample 9 10 11 year 11 year 13 sample 12 longitudinal 13 sample 13 sample 16 = 14 ( 16 = 15 n 16 = 16 = 17 512 16 = 18 ) 19 , 28 and 20 a 21 subset 21 subset 22 of 21 subset 28 and 22 of 27 health 23 the 27 health 24 long 25 - 24 long 27 health 26 running 27 health 28 and 30 study 28 and 31 of 29 retirement 30 study 31 of 32 aging 32 aging 33 adults measures included an adjective - rating measure [of] conscientiousness , self - reported health conditions , and three measures of cognitive functioning ( word recall , delayed recall , and vocabulary ) included in the 1996 wave of the hrs study . 0 ###LEFT-WALL### 1 measures 0 ###LEFT-WALL### 2 included 0 ###LEFT-WALL### 10 , 1 measures 2 included 2 included 4 adjective 2 included 6 rating 3 an 4 adjective 5 - 6 rating 6 rating 9 conscientiousness 6 rating 10 , 7 measure 9 conscientiousness 10 , 11 self 10 , 12 - 12 - 17 and 13 reported 14 health 14 health 15 conditions 15 conditions 17 and 16 , 17 and 17 and 19 measures 18 three 19 measures 19 measures 20 of 20 of 22 functioning 21 cognitive 22 functioning 22 functioning 25 recall 22 functioning 30 and 23 ( 25 recall 24 word 25 recall 25 recall 26 , 26 , 30 and 27 delayed 28 recall 28 recall 30 and 29 , 30 and 30 and 31 vocabulary 30 and 32 ) 30 and 33 included 30 and 34 in 30 and 42 . 34 in 37 wave 35 the 37 wave 36 1996 37 wave 37 wave 38 of 38 of 41 study 39 the 41 study 40 hrs 41 study results : our results found that conscientiousness significantly predicted greater longevity , even in a model including the two proposed mediator variables , gender , age , and years of education . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 1 results 2 : 2 : 4 results 3 our 4 results 4 results 5 found 4 results 6 that 4 results 9 predicted 4 results 13 even 6 that 7 conscientiousness 6 that 9 predicted 7 conscientiousness 9 predicted 8 significantly 9 predicted 9 predicted 11 longevity 10 greater 11 longevity 12 , 13 even 13 even 14 in 13 even 32 . 14 in 16 model 15 a 16 model 16 model 17 including 16 model 28 and 17 including 22 variables 18 the 19 two 19 two 22 variables 20 proposed 21 mediator 21 mediator 22 variables 23 , 28 and 24 gender 25 , 25 , 26 age 25 , 28 and 27 , 28 and 28 and 29 years 28 and 32 . 29 years 30 of 30 of 31 education moreover , cognitive functioning appears to partially mediate this relationship . 0 ###LEFT-WALL### 4 functioning 0 ###LEFT-WALL### 5 appears 0 ###LEFT-WALL### 11 . 1 moreover 2 , 1 moreover 4 functioning 3 cognitive 4 functioning 4 functioning 5 appears 5 appears 6 to 5 appears 8 mediate 6 to 8 mediate 7 partially 8 mediate 8 mediate 10 relationship 9 this 10 relationship conclusions : this study replicates previous research showing that conscientious individuals tend to lead longer lives , and provides further insight into why this effect occurs . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 27 . 2 : 4 study 2 : 5 replicates 3 this 4 study 4 study 5 replicates 5 replicates 7 research 6 previous 7 research 7 research 8 showing 8 showing 11 individuals 8 showing 18 and 9 that 10 conscientious 10 conscientious 11 individuals 11 individuals 18 and 12 tend 13 to 12 tend 14 lead 12 tend 18 and 13 to 14 lead 14 lead 15 longer 14 lead 16 lives 17 , 18 and 18 and 19 provides 19 provides 21 insight 19 provides 22 into 20 further 21 insight 22 into 23 why 23 why 25 effect 23 why 26 occurs 24 this 25 effect 25 effect 26 occurs in addition , it underscores the importance of measurement considerations . 0 ###LEFT-WALL### 4 it 0 ###LEFT-WALL### 5 underscores 0 ###LEFT-WALL### 11 . 1 in 2 addition 1 in 3 , 1 in 4 it 4 it 5 underscores 5 underscores 7 importance 6 the 7 importance 7 importance 8 of 8 of 10 considerations 9 measurement 10 considerations objective : subjective well - being ( swb ) is an important predictor of mortality . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 5 - 1 objective 2 : 2 : 3 subjective 3 subjective 4 well 5 - 6 being 5 - 10 is 5 - 16 . 6 being 8 swb 6 being 10 is 7 ( 8 swb 8 swb 9 ) 10 is 13 predictor 11 an 12 important 11 an 13 predictor 12 important 13 predictor 13 predictor 14 of 14 of 15 mortality to date , surprisingly little is known about whether cognitive and emotional facets of swb independently predict mortality , and whether such effects vary by age . 0 ###LEFT-WALL### 1 to 0 ###LEFT-WALL### 2 date 0 ###LEFT-WALL### 3 , 0 ###LEFT-WALL### 27 . 1 to 2 date 3 , 5 little 3 , 7 known 4 surprisingly 5 little 5 little 6 is 6 is 7 known 7 known 8 about 8 about 9 whether 9 whether 13 facets 9 whether 17 predict 10 cognitive 11 and 11 and 12 emotional 11 and 13 facets 13 facets 14 of 13 facets 17 predict 14 of 15 swb 16 independently 17 predict 17 predict 20 and 17 predict 25 by 18 mortality 20 and 19 , 20 and 20 and 21 whether 20 and 23 effects 20 and 24 vary 22 such 23 effects 23 effects 24 vary 25 by 26 age method : this study examined differential effects of life satisfaction ( ls ) , positive [affect] [(] pa [ )(, and negative affect [(] [na] [ )(on mortality in a conjoint analysis using data of german adults between the ages of 40 to 85 years ( n = 3,124 [ )( 0 ###LEFT-WALL### 1 method 0 ###LEFT-WALL### 2 : 2 : 4 study 2 : 5 examined 2 : 14 , 3 this 4 study 4 study 5 examined 5 examined 7 effects 6 differential 7 effects 7 effects 8 of 7 effects 12 ls 8 of 10 satisfaction 9 life 10 satisfaction 11 ( 12 ls 12 ls 13 ) 14 , 21 and 14 , 23 affect 15 positive 18 pa 18 pa 21 and 20 )(, 21 and 21 and 22 negative 21 and 23 affect 23 affect 27 )(on 23 affect 32 analysis 23 affect 33 using 27 )(on 28 mortality 28 mortality 29 in 29 in 31 conjoint 30 a 31 conjoint 33 using 34 data 33 using 43 to 34 data 35 of 34 data 38 between 34 data 41 of 35 of 37 adults 36 german 37 adults 38 between 40 ages 39 the 40 ages 41 of 42 40 43 to 45 years 44 85 45 years 45 years 48 = 46 ( 48 = 47 n 48 = 48 = 49 3,124 48 = 51 )( effects of swb facets were analyzed using cox proportional hazards models . 0 ###LEFT-WALL### 1 effects 0 ###LEFT-WALL### 6 analyzed 0 ###LEFT-WALL### 12 . 1 effects 2 of 1 effects 5 were 2 of 4 facets 3 swb 4 facets 5 were 6 analyzed 6 analyzed 7 using 7 using 11 models 8 cox 9 proportional 9 proportional 10 hazards 10 hazards 11 models results : ls and pa predicted mortality over [and] above sociodemographic factors and physical health [(] hrls = . 89 , 95 % ci = . 79 - 1.00 , [p] < . 05 , hrpa = . 81 , 95 % ci = . 70 - ..y 93 [,] p [<] . 05 [ )( 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 19 . 0 ###LEFT-WALL### 33 . 1 results 2 : 2 : 7 mortality 2 : 8 over 3 ls 4 and 4 and 5 pa 5 pa 6 predicted 6 predicted 7 mortality 8 over 10 above 10 above 13 and 11 sociodemographic 12 factors 12 factors 13 and 13 and 15 health 13 and 17 hrls 13 and 18 = 14 physical 15 health 17 hrls 18 = 19 . 20 89 19 . 21 , 19 . 26 . 21 , 24 ci 21 , 25 = 22 95 24 ci 23 % 24 ci 24 ci 25 = 26 . 27 79 26 . 32 < 27 79 29 1.00 27 79 32 < 28 - 29 1.00 29 1.00 30 , 33 . 36 hrpa 33 . 37 = 33 . 38 . 34 05 36 hrpa 35 , 36 hrpa 36 hrpa 37 = 38 . 39 81 38 . 40 , 38 . 45 . 40 , 43 ci 40 , 44 = 41 95 43 ci 42 % 43 ci 43 ci 44 = 45 . 46 70 45 . 47 - 45 . 53 . 45 . 56 )( 46 70 47 - 47 - 48 ..y 48 ..y 49 93 49 93 51 p 53 . 54 05 however , this effect diminished when including self [-] rated health and physical activity . 0 ###LEFT-WALL### 4 effect 0 ###LEFT-WALL### 5 diminished 0 ###LEFT-WALL### 15 . 1 however 2 , 1 however 4 effect 3 this 4 effect 4 effect 5 diminished 5 diminished 6 when 6 when 7 including 7 including 12 and 8 self 10 rated 10 rated 11 health 11 health 12 and 12 and 14 activity 13 physical 14 activity [na] was [not] associated [with] mortality . 0 ###LEFT-WALL### 2 was 0 ###LEFT-WALL### 7 . 2 was 6 mortality 4 associated 6 mortality age group comparative analyses revealed that pa predicted mortality in older adults ( 65+ ) even after controlling for self [-] rated health and physical activity [(] hrpa = . 82 , 95 % ci = . 70 - ..y 97 [,] p [<] . 05 [ )( 0 ###LEFT-WALL### 1 age 0 ###LEFT-WALL### 8 predicted 0 ###LEFT-WALL### 30 . 1 age 4 analyses 1 age 5 revealed 1 age 8 predicted 2 group 4 analyses 3 comparative 4 analyses 4 analyses 5 revealed 5 revealed 7 pa 6 that 7 pa 8 predicted 9 mortality 9 mortality 10 in 9 mortality 16 even 9 mortality 19 for 10 in 12 adults 11 older 12 adults 12 adults 14 65+ 13 ( 14 65+ 14 65+ 15 ) 16 even 17 after 17 after 18 controlling 19 for 24 and 20 self 22 rated 22 rated 23 health 23 health 24 and 24 and 26 activity 24 and 28 hrpa 24 and 29 = 25 physical 26 activity 28 hrpa 29 = 30 . 31 82 30 . 32 , 30 . 37 . 32 , 35 ci 32 , 36 = 33 95 35 ci 34 % 35 ci 35 ci 36 = 37 . 38 70 37 . 39 - 37 . 45 . 38 70 39 - 39 - 40 ..y 40 ..y 41 97 41 97 43 p 45 . 46 05 45 . 48 )( in middle - aged participants , no swb indicator predicted mortality when [controlling] for covariates . 0 ###LEFT-WALL### 2 middle 0 ###LEFT-WALL### 3 - 1 in 2 middle 3 - 5 participants 3 - 6 , 3 - 16 . 4 aged 5 participants 6 , 9 indicator 6 , 10 predicted 7 no 9 indicator 8 swb 9 indicator 9 indicator 10 predicted 10 predicted 11 mortality 10 predicted 12 when 12 when 14 for 14 for 15 covariates conclusions : these findings suggest a differential impact of cognitive and emotional well - being on mortality and suggest that [in] middle - aged adults the effects of swb on mortality are attenuated by [self] - rated health and physical activity . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 42 . 2 : 4 findings 2 : 18 and 2 : 36 - 3 these 4 findings 4 findings 18 and 5 suggest 8 impact 5 suggest 18 and 6 a 7 differential 6 a 8 impact 7 differential 8 impact 8 impact 9 of 9 of 11 and 10 cognitive 11 and 11 and 13 well 11 and 14 - 11 and 15 being 12 emotional 13 well 15 being 16 on 16 on 17 mortality 18 and 19 suggest 19 suggest 22 middle 20 that 22 middle 22 middle 25 adults 23 - 25 adults 24 aged 25 adults 25 adults 27 effects 25 adults 34 by 25 adults 36 - 26 the 27 effects 27 effects 28 of 27 effects 32 are 28 of 29 swb 29 swb 30 on 30 on 31 mortality 32 are 33 attenuated 33 attenuated 34 by 36 - 39 and 37 rated 38 health 38 health 39 and 39 and 41 activity 40 physical 41 activity the study underscores the importance of swb for health and longevity , particularly for older adults . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 underscores 0 ###LEFT-WALL### 17 . 1 the 2 study 2 study 3 underscores 3 underscores 5 importance 3 underscores 13 particularly 4 the 5 importance 5 importance 6 of 6 of 7 swb 7 swb 8 for 8 for 10 and 9 health 10 and 10 and 11 longevity 10 and 12 , 13 particularly 14 for 14 for 16 adults 15 older 16 adults objectives : this longitudinal study examined the associations between older adults ' goal adjustment capacities ( i.e [.] , goal disengagement and goal reengagement capacities ) , functional disability , and depressive symptoms . 0 ###LEFT-WALL### 1 objectives 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 34 . 2 : 5 study 2 : 6 examined 2 : 27 , 3 this 5 study 4 longitudinal 5 study 5 study 6 examined 6 examined 8 associations 6 examined 9 between 7 the 8 associations 9 between 15 capacities 10 older 11 adults 11 adults 12 ' 12 ' 15 capacities 13 goal 14 adjustment 14 adjustment 15 capacities 15 capacities 17 i.e 15 capacities 25 capacities 16 ( 17 i.e 17 i.e 19 , 19 , 25 capacities 20 goal 21 disengagement 21 disengagement 22 and 22 and 23 goal 22 and 25 capacities 24 reengagement 25 capacities 25 capacities 26 ) 27 , 31 and 28 functional 29 disability 29 disability 31 and 30 , 31 and 31 and 33 symptoms 32 depressive 33 symptoms it was expected that goal disengagement capacities would prevent an adverse effect of heightened functional disability on increases in depressive symptoms . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 3 expected 0 ###LEFT-WALL### 22 . 1 it 2 was 2 was 3 expected 3 expected 4 that 4 that 7 capacities 4 that 9 prevent 5 goal 7 capacities 6 disengagement 7 capacities 7 capacities 8 would 8 would 9 prevent 9 prevent 12 effect 9 prevent 17 on 9 prevent 19 in 10 an 11 adverse 10 an 12 effect 11 adverse 12 effect 12 effect 13 of 13 of 16 disability 14 heightened 16 disability 15 functional 16 disability 17 on 18 increases 19 in 21 symptoms 20 depressive 21 symptoms method : multivariate regression analyses were conducted , using four waves of data from a six [-] year longitudinal study of 135 [community] - dwelling older adults ( >60 years old ) . 0 ###LEFT-WALL### 1 method 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 24 - 0 ###LEFT-WALL### 33 . 1 method 2 : 2 : 3 multivariate 2 : 9 using 3 multivariate 4 regression 3 multivariate 7 conducted 4 regression 5 analyses 4 regression 6 were 4 regression 7 conducted 5 analyses 6 were 8 , 9 using 9 using 11 waves 9 using 14 from 9 using 24 - 10 four 11 waves 11 waves 12 of 12 of 13 data 14 from 20 study 15 a 20 study 16 six 18 year 18 year 20 study 19 longitudinal 20 study 20 study 21 of 21 of 22 135 24 - 27 adults 25 dwelling 27 adults 26 older 27 adults 27 adults 29 >60 28 ( 29 >60 29 >60 31 old 29 >60 32 ) 30 years 31 old results : depressive symptoms and functionality disability increased over time . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 11 . 2 : 5 and 3 depressive 4 symptoms 4 symptoms 5 and 5 and 7 disability 5 and 8 increased 6 functionality 7 disability 8 increased 9 over 9 over 10 time moreover , poor goal disengagement capacities and high levels of functional disability forecasted six - year increases in depressive symptoms . 0 ###LEFT-WALL### 7 and 0 ###LEFT-WALL### 13 forecasted 0 ###LEFT-WALL### 15 - 0 ###LEFT-WALL### 21 . 1 moreover 2 , 1 moreover 7 and 3 poor 4 goal 4 goal 6 capacities 5 disengagement 6 capacities 6 capacities 7 and 7 and 9 levels 7 and 10 of 7 and 13 forecasted 8 high 9 levels 10 of 12 disability 11 functional 12 disability 13 forecasted 14 six 15 - 17 increases 16 year 17 increases 17 increases 18 in 18 in 20 symptoms 19 depressive 20 symptoms finally , goal disengagement buffered the association of functional disability with increases in depressive symptoms . 0 ###LEFT-WALL### 4 disengagement 0 ###LEFT-WALL### 5 buffered 0 ###LEFT-WALL### 16 . 1 finally 2 , 1 finally 4 disengagement 3 goal 4 disengagement 4 disengagement 5 buffered 5 buffered 7 association 5 buffered 11 with 5 buffered 13 in 6 the 7 association 7 association 8 of 8 of 10 disability 9 functional 10 disability 11 with 12 increases 13 in 15 symptoms 14 depressive 15 symptoms no associations were found for goal reengagement capacities . 0 ###LEFT-WALL### 2 associations 0 ###LEFT-WALL### 4 found 0 ###LEFT-WALL### 9 . 1 no 2 associations 2 associations 3 were 3 were 4 found 4 found 5 for 5 for 8 capacities 6 goal 8 capacities 7 reengagement 8 capacities conclusion : the findings suggest an adaptive role for goal disengagement capacities in older adulthood . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 4 findings 2 : 5 suggest 2 : 16 . 3 the 4 findings 4 findings 5 suggest 5 suggest 8 role 5 suggest 13 in 6 an 7 adaptive 6 an 8 role 7 adaptive 8 role 8 role 9 for 9 for 12 capacities 10 goal 12 capacities 11 disengagement 12 capacities 13 in 15 adulthood 14 older 15 adulthood when confronted with increases in functional disability , the capacity to withdraw effort and commitment from unattainable goals can help protect older adults from experiencing long - term increases in depressive symptoms . 0 ###LEFT-WALL### 10 capacity 0 ###LEFT-WALL### 21 protect 0 ###LEFT-WALL### 33 . 1 when 2 confronted 1 when 8 , 1 when 10 capacity 2 confronted 3 with 2 confronted 5 in 3 with 4 increases 5 in 7 disability 6 functional 7 disability 9 the 10 capacity 10 capacity 11 to 10 capacity 12 withdraw 10 capacity 19 can 11 to 12 withdraw 12 withdraw 14 and 12 withdraw 16 from 13 effort 14 and 14 and 15 commitment 16 from 18 goals 17 unattainable 18 goals 19 can 20 help 20 help 21 protect 21 protect 23 adults 21 protect 24 from 22 older 23 adults 24 from 25 experiencing 25 experiencing 29 increases 25 experiencing 30 in 26 long 27 - 26 long 28 term 28 term 29 increases 30 in 32 symptoms 31 depressive 32 symptoms none none several studies have shown that total nephron [(] glomerular ) number varies widely in normal human kidneys . 0 ###LEFT-WALL### 1 none 0 ###LEFT-WALL### 6 shown 0 ###LEFT-WALL### 20 . 1 none 3 several 1 none 4 studies 1 none 5 have 2 none 3 several 3 several 4 studies 5 have 6 shown 6 shown 13 number 6 shown 14 varies 7 that 13 number 8 total 9 nephron 9 nephron 13 number 11 glomerular 12 ) 11 glomerular 13 number 13 number 14 varies 14 varies 15 widely 14 varies 16 in 16 in 19 kidneys 17 normal 19 kidneys 18 human 19 kidneys whereas the studies agree that average nephron number is approximately 900,000 to 1 million per kidney , numbers for individual kidneys range from approximately 200,000 to >2.5 [million] . 0 ###LEFT-WALL### 8 number 0 ###LEFT-WALL### 17 , 0 ###LEFT-WALL### 29 . 1 whereas 3 studies 1 whereas 4 agree 1 whereas 8 number 2 the 3 studies 3 studies 4 agree 5 that 8 number 6 average 7 nephron 7 nephron 8 number 8 number 17 , 9 is 14 million 9 is 17 , 10 approximately 11 900,000 11 900,000 12 to 12 to 13 1 12 to 14 million 14 million 15 per 15 per 16 kidney 17 , 18 numbers 17 , 19 for 17 , 22 range 19 for 21 kidneys 20 individual 21 kidneys 22 range 23 from 22 range 26 to 23 from 25 200,000 24 approximately 25 200,000 26 to 27 >2.5 several studies have shown loss of glomeruli due to age - related glomerulosclerosis . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 4 shown 0 ###LEFT-WALL### 12 related 1 several 2 studies 2 studies 3 have 3 have 4 shown 4 shown 5 loss 4 shown 9 to 5 loss 6 of 6 of 7 glomeruli 8 due 9 to 9 to 10 age 11 - 12 related 12 related 13 glomerulosclerosis 12 related 14 . the rates of loss vary among individuals depending upon blood pressure , diseases affecting the kidney , and other attributes of health , but most of the variation [in] nephron number is present at birth and is therefore developmentally determined . 0 ###LEFT-WALL### 2 rates 0 ###LEFT-WALL### 5 vary 0 ###LEFT-WALL### 24 but 0 ###LEFT-WALL### 40 determined 0 ###LEFT-WALL### 41 . 1 the 2 rates 2 rates 3 of 2 rates 5 vary 3 of 4 loss 5 vary 6 among 6 among 7 individuals 7 individuals 8 depending 7 individuals 9 upon 9 upon 18 and 10 blood 11 pressure 11 pressure 12 , 12 , 13 diseases 12 , 18 and 13 diseases 14 affecting 14 affecting 16 kidney 15 the 16 kidney 17 , 18 and 18 and 20 attributes 18 and 21 of 19 other 20 attributes 21 of 22 health 23 , 24 but 24 but 25 most 24 but 36 and 25 most 26 of 25 most 36 and 26 of 31 number 27 the 31 number 28 variation 31 number 30 nephron 31 number 32 is 33 present 32 is 36 and 33 present 34 at 34 at 35 birth 36 and 37 is 37 is 40 determined 38 therefore 40 determined 39 developmentally 40 determined for example , in a relatively small study of nephron number [in] 15 children < 3 months of age , we found that nephron number ranged from approximately 250,000 to 1.1 million . 0 ###LEFT-WALL### 14 children 0 ###LEFT-WALL### 26 ranged 0 ###LEFT-WALL### 33 . 1 for 2 example 2 example 3 , 2 example 14 children 4 in 8 study 4 in 14 children 5 a 6 relatively 5 a 8 study 6 relatively 7 small 7 small 8 study 8 study 9 of 9 of 11 number 10 nephron 11 number 11 number 13 15 14 children 17 months 14 children 25 number 14 children 26 ranged 15 < 16 3 16 3 17 months 17 months 21 we 17 months 22 found 17 months 25 number 18 of 19 age 18 of 20 , 18 of 21 we 21 we 22 found 22 found 24 nephron 23 that 24 nephron 26 ranged 27 from 27 from 32 million 28 approximately 29 250,000 29 250,000 30 to 30 to 31 1.1 30 to 32 million given that no new nephrons are formed in human kidneys after approximately 36 weeks ' gestation , much interest has focused on renal function [and] health in individuals born with relatively low nephron endowment . 0 ###LEFT-WALL### 1 given 0 ###LEFT-WALL### 17 , 0 ###LEFT-WALL### 35 . 1 given 2 that 1 given 6 are 1 given 8 in 3 no 5 nephrons 4 new 5 nephrons 5 nephrons 6 are 6 are 7 formed 8 in 10 kidneys 9 human 10 kidneys 10 kidneys 11 after 11 after 16 gestation 12 approximately 13 36 13 36 14 weeks 14 weeks 15 ' 15 ' 16 gestation 17 , 19 interest 17 , 21 focused 18 much 19 interest 19 interest 20 has 20 has 21 focused 21 focused 22 on 21 focused 27 in 22 on 26 health 23 renal 24 function 24 function 26 health 27 in 28 individuals 28 individuals 29 born 29 born 30 with 30 with 34 endowment 31 relatively 32 low 32 low 33 nephron 33 nephron 34 endowment several studies have reported a direct correlation between birth weight and nephron number and an indirect association between nephron number and blood pressure . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 4 reported 0 ###LEFT-WALL### 24 . 1 several 2 studies 2 studies 3 have 3 have 4 reported 4 reported 7 correlation 4 reported 8 between 4 reported 18 between 5 a 6 direct 5 a 7 correlation 6 direct 7 correlation 8 between 14 and 9 birth 10 weight 10 weight 11 and 11 and 13 number 11 and 14 and 12 nephron 13 number 14 and 17 association 15 an 16 indirect 15 an 17 association 16 indirect 17 association 18 between 21 and 19 nephron 20 number 20 number 21 and 21 and 23 pressure 22 blood 23 pressure associations between low birth weight and cardiovascular disease , including hypertension , have also been widely reported . 0 ###LEFT-WALL### 6 and 0 ###LEFT-WALL### 9 , 0 ###LEFT-WALL### 17 reported 0 ###LEFT-WALL### 18 . 1 associations 2 between 1 associations 6 and 2 between 5 weight 3 low 4 birth 4 birth 5 weight 6 and 8 disease 7 cardiovascular 8 disease 9 , 11 hypertension 9 , 12 , 10 including 11 hypertension 12 , 13 have 13 have 15 been 14 also 15 been 15 been 16 widely 15 been 17 reported this report provides an update on our current knowledge of human nephron number and the associations with adult health and disease . 0 ###LEFT-WALL### 2 report 0 ###LEFT-WALL### 3 provides 0 ###LEFT-WALL### 22 . 1 this 2 report 2 report 3 provides 3 provides 5 update 3 provides 6 on 3 provides 17 with 4 an 5 update 6 on 9 knowledge 7 our 9 knowledge 8 current 9 knowledge 9 knowledge 10 of 10 of 14 and 11 human 12 nephron 12 nephron 13 number 13 number 14 and 14 and 16 associations 15 the 16 associations 17 with 20 and 18 adult 19 health 19 health 20 and 20 and 21 disease during the last 50 - 60 years , due to development of medical care and hygienically safe living conditions , the average life span of european citizens has substantially increased , with a rapid growth of the population older than 65 years . 0 ###LEFT-WALL### 24 span 0 ###LEFT-WALL### 30 increased 1 during 7 years 1 during 8 , 1 during 24 span 2 the 3 last 2 the 5 - 4 50 5 - 5 - 6 60 5 - 7 years 9 due 10 to 10 to 15 and 10 to 24 span 11 development 12 of 11 development 15 and 12 of 14 care 13 medical 14 care 15 and 19 conditions 15 and 20 , 16 hygienically 17 safe 17 safe 19 conditions 18 living 19 conditions 21 the 24 span 22 average 24 span 23 life 24 span 24 span 25 of 24 span 28 has 25 of 27 citizens 26 european 27 citizens 28 has 30 increased 29 substantially 30 increased 30 increased 32 with 31 , 32 with 32 with 35 growth 32 with 43 . 33 a 35 growth 34 rapid 35 growth 35 growth 36 of 36 of 38 population 37 the 38 population 38 population 39 older 39 older 40 than 40 than 42 years 41 65 42 years this trend places ever [-] growing medical and economical burden on society , as many of the older subjects suffer from age - related diseases and frailty . 0 ###LEFT-WALL### 2 trend 0 ###LEFT-WALL### 3 places 0 ###LEFT-WALL### 13 , 1 this 2 trend 2 trend 3 places 3 places 10 burden 3 places 11 on 4 ever 6 growing 6 growing 10 burden 7 medical 8 and 8 and 9 economical 8 and 10 burden 11 on 12 society 13 , 20 suffer 13 , 23 - 14 as 15 many 14 as 20 suffer 15 many 16 of 16 of 19 subjects 17 the 19 subjects 18 older 19 subjects 20 suffer 21 from 21 from 22 age 23 - 26 and 23 - 28 . 24 related 25 diseases 25 diseases 26 and 26 and 27 frailty coping with these problems requires not only appropriate medical treatment and social support but also extensive research in many fields of aging - from biology to sociology , with involvement of older people as the research subjects . 0 ###LEFT-WALL### 1 coping 0 ###LEFT-WALL### 5 requires 0 ###LEFT-WALL### 38 . 1 coping 2 with 1 coping 5 requires 2 with 4 problems 3 these 4 problems 5 requires 14 but 5 requires 18 in 6 not 7 only 7 only 14 but 8 appropriate 10 treatment 9 medical 10 treatment 10 treatment 11 and 11 and 13 support 11 and 14 but 12 social 13 support 14 but 17 research 15 also 16 extensive 16 extensive 17 research 18 in 20 fields 19 many 20 fields 20 fields 21 of 20 fields 31 of 20 fields 34 as 21 of 22 aging 22 aging 24 from 22 aging 29 with 23 - 24 from 24 from 25 biology 24 from 28 , 25 biology 26 to 26 to 27 sociology 29 with 30 involvement 31 of 33 people 32 older 33 people 34 as 37 subjects 35 the 37 subjects 36 research 37 subjects this work anticipates development and application of ethical standards suited to dynamic advances in aging research . 0 ###LEFT-WALL### 2 work 0 ###LEFT-WALL### 3 anticipates 0 ###LEFT-WALL### 17 . 1 this 2 work 2 work 3 anticipates 3 anticipates 5 and 4 development 5 and 5 and 6 application 5 and 7 of 7 of 9 standards 8 ethical 9 standards 9 standards 10 suited 10 suited 11 to 10 suited 14 in 11 to 13 advances 12 dynamic 13 advances 14 in 15 aging 15 aging 16 research the aim of this review is to update the knowledge in ethical requirements toward recruitment [of] older research subjects , obtaining of informed consent , [collection] of biological samples , and use of stem cells in preclinical and clinical settings . 0 ###LEFT-WALL### 2 aim 0 ###LEFT-WALL### 41 . 1 the 2 aim 2 aim 3 of 2 aim 6 is 3 of 5 review 4 this 5 review 6 is 7 to 6 is 8 update 7 to 8 update 8 update 31 and 9 the 10 knowledge 10 knowledge 11 in 10 knowledge 20 , 11 in 13 requirements 12 ethical 13 requirements 13 requirements 14 toward 14 toward 19 subjects 15 recruitment 19 subjects 17 older 18 research 18 research 19 subjects 20 , 21 obtaining 20 , 31 and 21 obtaining 22 of 22 of 24 consent 23 informed 24 consent 24 consent 27 of 25 , 27 of 27 of 29 samples 27 of 30 , 28 biological 29 samples 31 and 32 use 31 and 33 of 33 of 35 cells 34 stem 35 cells 35 cells 36 in 36 in 40 settings 37 preclinical 38 and 38 and 39 clinical 38 and 40 settings it [is] concluded that application [of] adequate ethical platform markedly facilitates recruitment [of] older persons for participation in research . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 3 concluded 0 ###LEFT-WALL### 20 . 1 it 3 concluded 3 concluded 9 platform 3 concluded 11 facilitates 4 that 9 platform 5 application 9 platform 7 adequate 9 platform 8 ethical 9 platform 9 platform 11 facilitates 10 markedly 11 facilitates 11 facilitates 15 persons 11 facilitates 18 in 12 recruitment 15 persons 14 older 15 persons 15 persons 16 for 16 for 17 participation 18 in 19 research currently , the basic ethical concepts are subjected to extensive discussion , with participation of all interested parties , in order to guarantee successful research on problems of human aging , protect older people from undesired interference , and afford their benefits through supporting innovations in research , therapy , and care . 0 ###LEFT-WALL### 6 concepts 0 ###LEFT-WALL### 8 subjected 0 ###LEFT-WALL### 53 . 1 currently 2 , 1 currently 6 concepts 3 the 6 concepts 4 basic 6 concepts 5 ethical 6 concepts 6 concepts 7 are 7 are 8 subjected 8 subjected 9 to 8 subjected 13 with 8 subjected 20 in 9 to 11 discussion 10 extensive 11 discussion 12 , 13 with 13 with 14 participation 13 with 19 , 14 participation 15 of 15 of 18 parties 16 all 18 parties 17 interested 18 parties 20 in 21 order 21 order 22 to 21 order 31 , 22 to 31 , 23 guarantee 25 research 23 guarantee 26 on 23 guarantee 31 , 24 successful 25 research 26 on 27 problems 27 problems 28 of 28 of 30 aging 29 human 30 aging 31 , 39 and 32 protect 34 people 32 protect 35 from 32 protect 39 and 33 older 34 people 35 from 37 interference 36 undesired 37 interference 38 , 39 and 39 and 51 and 40 afford 42 benefits 40 afford 43 through 40 afford 46 in 40 afford 51 and 41 their 42 benefits 43 through 45 innovations 44 supporting 45 innovations 46 in 47 research 47 research 49 therapy 48 , 49 therapy 49 therapy 50 , 50 , 51 and 51 and 52 care objectives : ct colonography ( ctc ) is being increasingly used for the radiological evaluation of colorectal symptoms . 0 ###LEFT-WALL### 1 objectives 0 ###LEFT-WALL### 2 : 2 : 6 ctc 2 : 8 is 2 : 19 . 3 ct 4 colonography 4 colonography 6 ctc 5 ( 6 ctc 6 ctc 7 ) 6 ctc 8 is 8 is 9 being 9 being 11 used 10 increasingly 11 used 11 used 12 for 12 for 15 evaluation 13 the 15 evaluation 14 radiological 15 evaluation 15 evaluation 16 of 16 of 18 symptoms 17 colorectal 18 symptoms aim of this study was to assess the role of ctc in excluding a colorectal cancer ( crc ) in older symptomatic patients . 0 ###LEFT-WALL### 1 aim 0 ###LEFT-WALL### 24 . 1 aim 2 of 1 aim 5 was 2 of 4 study 3 this 4 study 5 was 6 to 5 was 7 assess 6 to 7 assess 7 assess 9 role 7 assess 12 in 8 the 9 role 9 role 10 of 10 of 11 ctc 12 in 13 excluding 13 excluding 16 cancer 13 excluding 20 in 14 a 15 colorectal 14 a 16 cancer 15 colorectal 16 cancer 16 cancer 18 crc 17 ( 18 crc 18 crc 19 ) 20 in 23 patients 21 older 23 patients 22 symptomatic 23 patients methods : 1,359 ctc studies performed between march 2002 and december 2007 were analysed retrospectively . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 16 . 2 : 10 and 2 : 14 analysed 3 1,359 5 studies 4 ctc 5 studies 5 studies 6 performed 5 studies 10 and 6 performed 7 between 7 between 8 march 8 march 9 2002 10 and 11 december 10 and 13 were 11 december 12 2007 13 were 14 analysed 14 analysed 15 retrospectively gold [standard] was an endoscopic examination within 1 year [and/or] clinical , [endoscopic] [and/or] [radiological] follow - up until the time of data analysis . 0 ###LEFT-WALL### 1 gold 0 ###LEFT-WALL### 3 was 0 ###LEFT-WALL### 12 , 0 ###LEFT-WALL### 25 . 1 gold 3 was 3 was 6 examination 3 was 7 within 3 was 11 clinical 4 an 5 endoscopic 4 an 6 examination 5 endoscopic 6 examination 7 within 9 year 8 1 9 year 12 , 16 follow 12 , 17 - 17 - 18 up 18 up 19 until 18 up 24 analysis 19 until 21 time 20 the 21 time 21 time 22 of 22 of 23 data patients not diagnosed as having a crc on ctc were assumed as true - negatives if the gold standard was negative and did not feature on the regional cancer registry ( at least 18 months post - ctc ) . 0 ###LEFT-WALL### 7 crc 0 ###LEFT-WALL### 10 were 1 patients 7 crc 2 not 3 diagnosed 2 not 7 crc 4 as 5 having 4 as 7 crc 6 a 7 crc 7 crc 8 on 7 crc 10 were 8 on 9 ctc 10 were 15 negatives 10 were 16 if 11 assumed 15 negatives 12 as 13 true 13 true 14 - 13 true 15 negatives 16 if 19 standard 16 if 22 and 17 the 19 standard 18 gold 19 standard 19 standard 22 and 20 was 21 negative 20 was 22 and 22 and 23 did 23 did 24 not 23 did 25 feature 25 feature 26 on 25 feature 30 registry 26 on 29 cancer 27 the 29 cancer 28 regional 29 cancer 30 registry 36 post 31 ( 36 post 32 at 33 least 33 least 34 18 34 18 35 months 35 months 36 post 36 post 38 ctc 36 post 40 . 37 - 38 ctc 38 ctc 39 ) sensitivity , specificity , positive and negative predictive values were calculated for detection of colorectal cancer . 0 ###LEFT-WALL### 6 and 0 ###LEFT-WALL### 11 calculated 0 ###LEFT-WALL### 17 . 1 sensitivity 2 , 2 , 3 specificity 2 , 4 , 4 , 5 positive 4 , 6 and 6 and 9 values 6 and 10 were 7 negative 9 values 8 predictive 9 values 10 were 11 calculated 11 calculated 12 for 12 for 13 detection 13 detection 14 of 14 of 16 cancer 15 colorectal 16 cancer results : after exclusions , 1,177 ctc studies were included . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 5 , 0 ###LEFT-WALL### 11 . 1 results 2 : 2 : 3 after 3 after 4 exclusions 5 , 8 studies 5 , 10 included 6 1,177 8 studies 7 ctc 8 studies 8 studies 9 were 9 were 10 included these were undertaken in 463 men and 714 women . 0 ###LEFT-WALL### 1 these 0 ###LEFT-WALL### 3 undertaken 0 ###LEFT-WALL### 10 . 1 these 2 were 2 were 3 undertaken 3 undertaken 4 in 4 in 7 and 5 463 6 men 6 men 7 and 7 and 9 women 8 714 9 women median age of patients undergoing ctc was 71 ( range , 27 - 96 ) years . 0 ###LEFT-WALL### 2 age 0 ###LEFT-WALL### 7 was 1 median 2 age 2 age 3 of 2 age 7 was 3 of 4 patients 4 patients 5 undergoing 5 undergoing 6 ctc 7 was 8 71 8 71 16 years 9 ( 16 years 10 range 16 years 11 , 13 - 12 27 13 - 13 - 14 96 13 - 15 ) 13 - 16 years 16 years 17 . median follow - up [was] 34.5 ( range 18 - 84 ) months . 0 ###LEFT-WALL### 2 follow 0 ###LEFT-WALL### 14 . 1 median 2 follow 2 follow 4 up 2 follow 13 months 3 - 4 up 4 up 6 34.5 4 up 12 ) 6 34.5 8 range 7 ( 8 range 8 range 10 - 8 range 12 ) 9 18 10 - 10 - 11 84 three small colorectal cancers were missed . 0 ###LEFT-WALL### 4 cancers 0 ###LEFT-WALL### 6 missed 0 ###LEFT-WALL### 7 . 1 three 4 cancers 2 small 4 cancers 3 colorectal 4 cancers 4 cancers 5 were 5 were 6 missed sensitivity and negative predictive value for crc were 94.9 % ( 95 % ci:84.9 [%] - 98.7 [%] [ )(and 99.7 % ( 95 % ci:99.1 [%] - 99.9 % ) respectively . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 8 were 0 ###LEFT-WALL### 33 . 1 sensitivity 2 and 2 and 5 value 2 and 6 for 2 and 8 were 3 negative 5 value 4 predictive 5 value 6 for 7 crc 8 were 10 % 8 were 32 respectively 9 94.9 10 % 10 % 14 ci:84.9 10 % 22 % 11 ( 14 ci:84.9 12 95 14 ci:84.9 13 % 14 ci:84.9 14 ci:84.9 16 - 16 - 22 % 17 98.7 20 )(and 20 )(and 21 99.7 20 )(and 22 % 22 % 26 ci:99.1 22 % 31 ) 23 ( 26 ci:99.1 24 95 26 ci:99.1 25 % 26 ci:99.1 26 ci:99.1 30 % 26 ci:99.1 31 ) 28 - 30 % 29 99.9 30 % 30 % 31 ) conclusions : ctc has a high sensitivity and negative predictive value in excluding a crc in patients with colorectal symptoms . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 3 ctc 2 : 4 has 2 : 21 . 3 ctc 4 has 4 has 8 and 5 a 6 high 5 a 7 sensitivity 6 high 7 sensitivity 7 sensitivity 8 and 8 and 11 value 8 and 12 in 8 and 16 in 8 and 18 with 9 negative 11 value 10 predictive 11 value 12 in 13 excluding 13 excluding 15 crc 14 a 15 crc 16 in 17 patients 18 with 20 symptoms 19 colorectal 20 symptoms purpose : to examine the association between self [-] assessed quality of life ( qol ) and perceived neighborhood safety , social cohesion , and walkability among older adults in new york city ( nyc ) . 0 ###LEFT-WALL### 1 purpose 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 37 . 2 : 3 to 2 : 17 and 3 to 17 and 4 examine 6 association 4 examine 7 between 4 examine 17 and 5 the 6 association 7 between 11 quality 8 self 10 assessed 10 assessed 11 quality 11 quality 12 of 11 quality 15 qol 12 of 13 life 14 ( 15 qol 15 qol 16 ) 17 and 18 perceived 17 and 27 among 17 and 30 in 18 perceived 25 and 19 neighborhood 20 safety 20 safety 21 , 21 , 23 cohesion 21 , 25 and 22 social 23 cohesion 24 , 25 and 25 and 26 walkability 27 among 29 adults 28 older 29 adults 30 in 35 nyc 31 new 32 york 32 york 33 city 33 city 35 nyc 34 ( 35 nyc 35 nyc 36 ) methods : we used data from the 2008 health indicators project , a cross - sectional survey of 1,870 older adults attending 56 nyc senior centers . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 3 we 2 : 4 used 2 : 27 . 3 we 4 used 4 used 5 data 5 data 6 from 5 data 18 of 6 from 17 survey 7 the 17 survey 8 2008 9 health 9 health 10 indicators 10 indicators 11 project 11 project 14 cross 11 project 17 survey 12 , 14 cross 13 a 14 cross 14 cross 15 - 16 sectional 17 survey 18 of 21 adults 19 1,870 21 adults 20 older 21 adults 21 adults 22 attending 22 attending 26 centers 23 56 26 centers 24 nyc 26 centers 25 senior 26 centers qol , a binary measure , was created by dichotomizing [a] 5 - point likert - scaled global assessment . 0 ###LEFT-WALL### 1 qol 0 ###LEFT-WALL### 8 created 0 ###LEFT-WALL### 13 - 0 ###LEFT-WALL### 20 . 1 qol 5 measure 1 qol 7 was 2 , 5 measure 3 a 4 binary 3 a 5 measure 4 binary 5 measure 5 measure 6 , 7 was 8 created 8 created 9 by 9 by 10 dichotomizing 10 dichotomizing 12 5 13 - 14 point 13 - 16 - 14 point 15 likert 16 - 19 assessment 17 scaled 19 assessment 18 global 19 assessment neighborhood safety , social cohesion , and walkability were multi - component scale variables that were standardized due to varying response metrics . 0 ###LEFT-WALL### 7 and 0 ###LEFT-WALL### 9 were 0 ###LEFT-WALL### 23 . 1 neighborhood 2 safety 2 safety 3 , 3 , 5 cohesion 3 , 7 and 4 social 5 cohesion 6 , 7 and 7 and 8 walkability 7 and 9 were 9 were 14 variables 10 multi 11 - 10 multi 14 variables 12 component 14 variables 13 scale 14 variables 14 variables 15 that 14 variables 16 were 15 that 16 were 16 were 17 standardized 17 standardized 18 due 18 due 19 to 19 to 20 varying 20 varying 22 metrics 21 response 22 metrics multivariate binomial logistic regression analysis was performed on 1,660 participants with complete data . 0 ###LEFT-WALL### 5 analysis 0 ###LEFT-WALL### 7 performed 0 ###LEFT-WALL### 14 . 1 multivariate 4 regression 2 binomial 3 logistic 3 logistic 4 regression 4 regression 5 analysis 5 analysis 6 was 6 was 7 performed 7 performed 8 on 7 performed 11 with 8 on 10 participants 9 1,660 10 participants 11 with 13 data 12 complete 13 data results : after adjusting for covariates , qol was significantly associated with neighborhood safety and social cohesion . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 7 , 0 ###LEFT-WALL### 18 . 1 results 2 : 2 : 3 after 3 after 4 adjusting 4 adjusting 5 for 5 for 6 covariates 7 , 8 qol 7 , 11 associated 8 qol 9 was 9 was 10 significantly 9 was 11 associated 11 associated 12 with 12 with 15 and 13 neighborhood 14 safety 14 safety 15 and 15 and 17 cohesion 16 social 17 cohesion a one - standard deviation increase in neighborhood safety and social cohesion increased [the] log odds [of] having higher qol by 30 % ( odds ratio ( or ) = 1.30 [;] 95 % confidence interval [(] ci [ )(= [1.14] [,] [1.48] [;] [p] [≤] 0.001 [ )(and 36 % [(] or [=] 1.36 [;] 95 % ci = 1.16 , 1.59 [;] [p] ≤ 0.001 ) , respectively . 0 ###LEFT-WALL### 2 one 0 ###LEFT-WALL### 3 - 1 a 2 one 3 - 6 increase 3 - 10 and 4 standard 5 deviation 5 deviation 6 increase 6 increase 7 in 7 in 9 safety 8 neighborhood 9 safety 10 and 20 qol 11 social 13 increased 12 cohesion 13 increased 13 increased 15 log 15 log 20 qol 16 odds 20 qol 18 having 20 qol 19 higher 20 qol 20 qol 21 by 20 qol 30 = 21 by 23 % 22 30 23 % 23 % 26 ratio 24 ( 26 ratio 25 odds 26 ratio 26 ratio 28 or 26 ratio 29 ) 27 ( 28 or 28 or 29 ) 30 = 38 ci 31 1.30 35 confidence 33 95 34 % 34 % 35 confidence 35 confidence 36 interval 36 interval 38 ci 38 ci 49 )(and 40 )(= 47 0.001 47 0.001 49 )(and 49 )(and 50 36 50 36 51 % 51 % 59 ci 53 or 59 ci 55 1.36 59 ci 57 95 59 ci 58 % 59 ci 59 ci 60 = 60 = 61 1.16 60 = 70 respectively 61 1.16 66 ≤ 62 , 66 ≤ 63 1.59 66 ≤ 66 ≤ 67 0.001 66 ≤ 68 ) 69 , 70 respectively 70 respectively 71 . higher qol was not significantly associated with neighborhood walkability . 0 ###LEFT-WALL### 2 qol 0 ###LEFT-WALL### 6 associated 0 ###LEFT-WALL### 10 . 1 higher 2 qol 2 qol 3 was 3 was 4 not 3 was 6 associated 5 significantly 6 associated 6 associated 7 with 7 with 9 walkability 8 neighborhood 9 walkability conclusion : the results of this study underscore the need for initiatives that focus on enhancing age - friendly neighborhood features in large urban centers such as nyc [and] [beyond] . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 31 . 2 : 4 results 2 : 8 underscore 2 : 18 - 3 the 4 results 4 results 5 of 4 results 8 underscore 5 of 7 study 6 this 7 study 8 underscore 10 need 8 underscore 15 on 9 the 10 need 10 need 11 for 11 for 12 initiatives 12 initiatives 13 that 12 initiatives 14 focus 13 that 14 focus 15 on 16 enhancing 16 enhancing 17 age 18 - 21 features 19 friendly 20 neighborhood 20 neighborhood 21 features 21 features 22 in 22 in 25 centers 23 large 25 centers 24 urban 25 centers 25 centers 27 as 26 such 27 as 27 as 28 nyc decreases in systemic and cellular levels of zinc ( zn ( 2+ ) ) during normal aging correlate with several age - related pathologies including age - related macular degeneration . 0 ###LEFT-WALL### 1 decreases 0 ###LEFT-WALL### 18 correlate 0 ###LEFT-WALL### 28 related 1 decreases 2 in 1 decreases 7 of 1 decreases 15 during 1 decreases 18 correlate 2 in 6 levels 3 systemic 4 and 4 and 5 cellular 4 and 6 levels 7 of 8 zinc 8 zinc 10 zn 9 ( 10 zn 10 zn 12 2+ 10 zn 14 ) 11 ( 12 2+ 12 2+ 13 ) 15 during 17 aging 16 normal 17 aging 18 correlate 19 with 19 with 21 age 19 with 25 including 20 several 21 age 22 - 23 related 23 related 24 pathologies 23 related 25 including 25 including 26 age 27 - 28 related 28 related 30 degeneration 28 related 31 . 29 macular 30 degeneration zn ( 2+ ) homeostasis in tissues [is] not [only] dependent on dietary intake but also on optimal expression and function of its influx ( zip ) and [efflux] [(] znt ) transporters . 0 ###LEFT-WALL### 33 transporters 0 ###LEFT-WALL### 34 . 1 zn 5 homeostasis 1 zn 28 and 2 ( 5 homeostasis 3 2+ 4 ) 3 2+ 5 homeostasis 5 homeostasis 15 but 5 homeostasis 27 ) 6 in 7 tissues 6 in 15 but 7 tissues 9 not 9 not 11 dependent 11 dependent 12 on 12 on 14 intake 13 dietary 14 intake 15 but 16 also 15 but 17 on 17 on 20 and 18 optimal 19 expression 19 expression 20 and 20 and 21 function 20 and 22 of 20 and 26 zip 22 of 24 influx 23 its 24 influx 25 ( 26 zip 26 zip 27 ) 28 and 31 znt 28 and 32 ) 28 and 33 transporters we recently showed that many of the zn ( 2+ ) transporters are expressed by the retinal pigment epithelial ( rpe ) cells . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 showed 0 ###LEFT-WALL### 24 . 1 we 3 showed 2 recently 3 showed 3 showed 5 many 3 showed 12 transporters 3 showed 14 expressed 4 that 5 many 5 many 6 of 5 many 10 2+ 6 of 8 zn 7 the 8 zn 9 ( 10 2+ 10 2+ 11 ) 12 transporters 13 are 13 are 14 expressed 14 expressed 15 by 15 by 23 cells 16 the 23 cells 17 retinal 18 pigment 18 pigment 23 cells 19 epithelial 21 rpe 19 epithelial 23 cells 20 ( 21 rpe 21 rpe 22 ) in this study , we present evidence that rpe cells contain less endogenous zn ( 2+ ) with increased aging and transport this ion vectorially with greater transport from the basal to apical direction . 0 ###LEFT-WALL### 5 we 0 ###LEFT-WALL### 21 and 0 ###LEFT-WALL### 35 . 1 in 3 study 1 in 4 , 1 in 5 we 2 this 3 study 5 we 21 and 6 present 7 evidence 6 present 21 and 7 evidence 8 that 8 that 9 rpe 8 that 19 increased 9 rpe 10 cells 9 rpe 18 with 9 rpe 19 increased 10 cells 11 contain 11 contain 14 zn 11 contain 18 with 12 less 14 zn 13 endogenous 14 zn 14 zn 16 2+ 15 ( 16 2+ 16 2+ 17 ) 19 increased 20 aging 21 and 22 transport 22 transport 24 ion 22 transport 25 vectorially 22 transport 26 with 22 transport 29 from 23 this 24 ion 26 with 28 transport 27 greater 28 transport 29 from 31 basal 30 the 31 basal 31 basal 32 to 32 to 34 direction 33 apical 34 direction expression of two zn ( 2+ ) influx transporters , zip2 and zip4 , is reduced as a function of rpe age . 0 ###LEFT-WALL### 1 expression 0 ###LEFT-WALL### 16 reduced 0 ###LEFT-WALL### 23 . 1 expression 2 of 1 expression 15 is 2 of 4 zn 3 two 4 zn 4 zn 12 and 5 ( 12 and 6 2+ 7 ) 6 2+ 8 influx 8 influx 9 transporters 9 transporters 10 , 10 , 11 zip2 10 , 12 and 12 and 13 zip4 12 and 14 , 15 is 16 reduced 16 reduced 17 as 17 as 19 function 18 a 19 function 19 function 20 of 20 of 22 age 21 rpe 22 age gene silencing of zip2 and zip4 in rpe cells from young donors or their overexpression in cells from older donors confirms that these two transporters are essential in controlling zn ( 2+ ) influx [and] sequestration in rpe cells . 0 ###LEFT-WALL### 2 silencing 0 ###LEFT-WALL### 21 confirms 1 gene 2 silencing 2 silencing 3 of 2 silencing 7 in 2 silencing 21 confirms 3 of 5 and 4 zip2 5 and 5 and 6 zip4 7 in 9 cells 8 rpe 9 cells 9 cells 10 from 10 from 13 or 11 young 12 donors 12 donors 13 or 13 or 15 overexpression 13 or 18 from 14 their 15 overexpression 15 overexpression 16 in 16 in 17 cells 18 from 20 donors 19 older 20 donors 21 confirms 22 that 22 that 25 transporters 22 that 26 are 23 these 24 two 24 two 25 transporters 25 transporters 26 are 26 are 27 essential 27 essential 28 in 28 in 29 controlling 29 controlling 30 zn 30 zn 36 sequestration 31 ( 36 sequestration 32 2+ 33 ) 32 2+ 34 influx 34 influx 36 sequestration 36 sequestration 37 in 36 sequestration 40 . 37 in 39 cells 38 rpe 39 cells both transporters are distributed on the basal surface of the rpe where they are likely to control zn ( 2+ ) homeostasis in the outer retina . 0 ###LEFT-WALL### 2 transporters 0 ###LEFT-WALL### 4 distributed 1 both 2 transporters 2 transporters 3 are 3 are 4 distributed 4 distributed 5 on 4 distributed 16 to 5 on 8 surface 6 the 8 surface 7 basal 8 surface 8 surface 9 of 9 of 11 rpe 10 the 11 rpe 11 rpe 12 where 12 where 13 they 12 where 14 are 13 they 14 are 14 are 15 likely 16 to 17 control 17 control 18 zn 18 zn 22 homeostasis 19 ( 22 homeostasis 20 2+ 21 ) 20 2+ 22 homeostasis 22 homeostasis 23 in 22 homeostasis 27 . 23 in 26 retina 24 the 26 retina 25 outer 26 retina chronic heart failure ( hf ) is a cardiovascular disease of cardinal importance because of several factors [:] [a] [ )( increasing occurrence due to the aging of the population , primary and secondary prevention of cardiovascular events , and modern advances in therapy , [b] [ )(a bad prognosis : around 65 % of patients [are] dead within 5 years of diagnosis , [c] [ )( high economic cost [:] hf accounts for 1 % to 2 % of total health care expenditure . 1 chronic 3 failure 2 heart 3 failure 3 failure 5 hf 3 failure 7 is 4 ( 5 hf 5 hf 6 ) 7 is 10 disease 7 is 14 because 8 a 10 disease 9 cardiovascular 10 disease 10 disease 11 of 11 of 13 importance 12 cardinal 13 importance 14 because 15 of 15 of 17 factors 16 several 17 factors 17 factors 22 increasing 22 increasing 23 occurrence 23 occurrence 24 due 24 due 25 to 25 to 27 aging 26 the 27 aging 27 aging 28 of 27 aging 36 of 28 of 33 and 29 the 30 population 30 population 31 , 31 , 32 primary 31 , 33 and 33 and 35 prevention 34 secondary 35 prevention 36 of 40 and 37 cardiovascular 38 events 38 events 40 and 39 , 40 and 40 and 42 advances 40 and 45 , 40 and 50 prognosis 40 and 51 : 40 and 52 around 41 modern 42 advances 42 advances 43 in 43 in 44 therapy 48 )(a 50 prognosis 49 bad 50 prognosis 50 prognosis 51 : 52 around 54 % 53 65 54 % 54 % 55 of 54 % 58 dead 54 % 62 of 55 of 56 patients 58 dead 59 within 59 within 61 years 60 5 61 years 62 of 63 diagnosis 63 diagnosis 73 accounts 64 , 73 accounts 68 high 73 accounts 69 economic 73 accounts 70 cost 73 accounts 72 hf 73 accounts 73 accounts 74 for 73 accounts 77 to 73 accounts 85 . 74 for 76 % 75 1 76 % 77 to 79 % 78 2 79 % 79 % 80 of 80 of 84 expenditure 81 total 82 health 82 health 84 expenditure 83 care 84 expenditure this review focuses on the main causes , consequences in terms of morbidity , mortality and costs and treatment of hf . 0 ###LEFT-WALL### 2 review 0 ###LEFT-WALL### 3 focuses 0 ###LEFT-WALL### 22 . 1 this 2 review 2 review 3 focuses 3 focuses 4 on 4 on 18 and 5 the 7 causes 6 main 7 causes 7 causes 8 , 8 , 9 consequences 8 , 14 , 9 consequences 10 in 10 in 11 terms 11 terms 12 of 12 of 13 morbidity 14 , 15 mortality 14 , 16 and 16 and 17 costs 16 and 18 and 18 and 19 treatment 18 and 20 of 20 of 21 hf a review of the current data on the cell density of normal adult human endothelial cells was carried out in order to establish some common parameters appearing in the different considered populations . 0 ###LEFT-WALL### 2 review 0 ###LEFT-WALL### 18 carried 0 ###LEFT-WALL### 33 . 1 a 2 review 2 review 3 of 2 review 17 was 3 of 6 data 4 the 6 data 5 current 6 data 6 data 7 on 7 on 10 density 8 the 10 density 9 cell 10 density 10 density 11 of 11 of 16 cells 12 normal 13 adult 13 adult 16 cells 14 human 16 cells 15 endothelial 16 cells 17 was 18 carried 18 carried 19 out 18 carried 20 in 20 in 21 order 21 order 22 to 21 order 23 establish 22 to 23 establish 23 establish 26 parameters 23 establish 31 considered 24 some 26 parameters 25 common 26 parameters 26 parameters 27 appearing 26 parameters 28 in 26 parameters 31 considered 28 in 30 different 29 the 30 different 31 considered 32 populations from the analysis of cell growth patterns , it is inferred that the cell aging rate is similar for each of the different considered populations . 0 ###LEFT-WALL### 9 it 0 ###LEFT-WALL### 11 inferred 0 ###LEFT-WALL### 26 . 1 from 3 analysis 1 from 8 , 1 from 9 it 2 the 3 analysis 3 analysis 4 of 4 of 7 patterns 5 cell 7 patterns 6 growth 7 patterns 9 it 10 is 10 is 11 inferred 11 inferred 12 that 12 that 16 rate 12 that 17 is 13 the 16 rate 14 cell 15 aging 15 aging 16 rate 16 rate 17 is 17 is 18 similar 18 similar 19 for 19 for 20 each 20 each 21 of 20 each 24 considered 21 of 23 different 22 the 23 different 24 considered 25 populations also , the morphology , the cell distribution and the tendency to hexagonallity are studied . 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 15 studied 0 ###LEFT-WALL### 16 . 1 also 2 , 1 also 9 and 3 the 4 morphology 4 morphology 5 , 5 , 8 distribution 5 , 9 and 6 the 8 distribution 7 cell 8 distribution 9 and 11 tendency 9 and 12 to 9 and 14 are 10 the 11 tendency 12 to 13 hexagonallity 14 are 15 studied the results are consistent with the hypothesis that this phenomenon is analogous with cell behavior in other structures such as dry foams and grains in polycrystalline materials . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 are 0 ###LEFT-WALL### 28 . 1 the 2 results 2 results 3 are 3 are 4 consistent 4 consistent 5 with 4 consistent 16 in 4 consistent 20 as 5 with 7 hypothesis 6 the 7 hypothesis 7 hypothesis 8 that 8 that 10 phenomenon 8 that 11 is 9 this 10 phenomenon 10 phenomenon 11 is 11 is 12 analogous 12 analogous 13 with 13 with 15 behavior 14 cell 15 behavior 16 in 18 structures 17 other 18 structures 19 such 20 as 20 as 23 and 21 dry 22 foams 22 foams 23 and 23 and 24 grains 23 and 25 in 25 in 27 materials 26 polycrystalline 27 materials therefore , its driving force may be controlled by the surface tension and the mobility of the boundaries . 0 ###LEFT-WALL### 5 force 0 ###LEFT-WALL### 8 controlled 0 ###LEFT-WALL### 19 . 1 therefore 2 , 1 therefore 5 force 3 its 5 force 4 driving 5 force 5 force 6 may 6 may 7 be 7 be 8 controlled 8 controlled 9 by 9 by 13 and 10 the 12 tension 11 surface 12 tension 12 tension 13 and 13 and 15 mobility 13 and 16 of 14 the 15 mobility 16 of 18 boundaries 17 the 18 boundaries background : leukocyte telomere length ( ltl ) is an emerging marker of biological age . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 5 length 2 : 9 is 2 : 16 . 3 leukocyte 5 length 4 telomere 5 length 5 length 7 ltl 5 length 9 is 6 ( 7 ltl 7 ltl 8 ) 9 is 12 marker 10 an 12 marker 11 emerging 12 marker 12 marker 13 of 13 of 15 age 14 biological 15 age chronic inflammatory activity is commonly proposed as a promoter of biological aging in general , and [of] leukocyte telomere shortening in particular . 0 ###LEFT-WALL### 3 activity 0 ###LEFT-WALL### 6 proposed 0 ###LEFT-WALL### 23 . 1 chronic 3 activity 2 inflammatory 3 activity 3 activity 4 is 4 is 6 proposed 5 commonly 6 proposed 6 proposed 7 as 7 as 16 and 8 a 9 promoter 9 promoter 10 of 9 promoter 16 and 10 of 12 aging 11 biological 12 aging 12 aging 14 general 13 in 14 general 15 , 16 and 16 and 19 telomere 16 and 22 particular 18 leukocyte 19 telomere 19 telomere 20 shortening 21 in 22 particular in addition , senescent cells with critically short telomeres produce pro [-] inflammatory factors . 0 ###LEFT-WALL### 5 cells 0 ###LEFT-WALL### 10 produce 0 ###LEFT-WALL### 15 . 1 in 2 addition 1 in 3 , 1 in 5 cells 4 senescent 5 cells 5 cells 6 with 5 cells 10 produce 6 with 9 telomeres 7 critically 8 short 8 short 9 telomeres 10 produce 14 factors 11 pro 14 factors 13 inflammatory 14 factors however , in spite of the proposed causal links between inflammatory activity and ltl , there is little clinical evidence in support of their covariation and interaction . 0 ###LEFT-WALL### 16 there 0 ###LEFT-WALL### 17 is 0 ###LEFT-WALL### 28 . 1 however 2 , 1 however 16 there 2 , 3 in 3 in 13 and 3 in 15 , 3 in 16 there 4 spite 5 of 4 spite 13 and 5 of 9 links 6 the 9 links 7 proposed 9 links 8 causal 9 links 9 links 10 between 10 between 12 activity 11 inflammatory 12 activity 13 and 14 ltl 16 there 17 is 17 is 20 evidence 18 little 20 evidence 19 clinical 20 evidence 20 evidence 21 in 20 evidence 23 of 21 in 22 support 23 of 26 and 24 their 25 covariation 25 covariation 26 and 26 and 27 interaction our sample included 1,962 high - functioning adults who participated in the health , aging and body composition study ( age range : 70 - 79 years ) . 0 ###LEFT-WALL### 2 sample 0 ###LEFT-WALL### 3 included 0 ###LEFT-WALL### 29 . 1 our 2 sample 2 sample 3 included 3 included 8 adults 4 1,962 8 adults 5 high 6 - 5 high 8 adults 7 functioning 8 adults 8 adults 9 who 8 adults 10 participated 9 who 10 participated 10 participated 11 in 11 in 16 and 12 the 13 health 13 health 14 , 14 , 15 aging 14 , 16 and 16 and 19 study 16 and 27 years 17 body 18 composition 18 composition 19 study 20 ( 27 years 21 age 22 range 22 range 23 : 23 : 25 - 24 70 25 - 25 - 26 79 26 79 27 years 27 years 28 ) logistic regression analyses indicated that individuals with high levels of either il - 6 [or] tnf - α had significantly higher odds for short ltl . 0 ###LEFT-WALL### 3 analyses 0 ###LEFT-WALL### 19 had 0 ###LEFT-WALL### 26 . 1 logistic 2 regression 2 regression 3 analyses 3 analyses 4 indicated 3 analyses 5 that 3 analyses 18 α 3 analyses 19 had 5 that 6 individuals 5 that 18 α 6 individuals 7 with 6 individuals 10 of 6 individuals 16 tnf 6 individuals 18 α 7 with 9 levels 8 high 9 levels 10 of 12 il 11 either 12 il 13 - 16 tnf 14 6 16 tnf 16 tnf 17 - 19 had 22 odds 19 had 23 for 20 significantly 21 higher 21 higher 22 odds 23 for 25 ltl 24 short 25 ltl in contrast , crp was not associated with ltl . 0 ###LEFT-WALL### 4 crp 0 ###LEFT-WALL### 5 was 0 ###LEFT-WALL### 10 . 1 in 2 contrast 1 in 3 , 1 in 4 crp 4 crp 5 was 5 was 6 not 5 was 8 with 6 not 7 associated 8 with 9 ltl conclusions/significance : results suggest that cumulative inflammatory load , as indexed by the combination of high levels of il - 6 and tnf - α , is associated with increased odds for short ltl . 0 ###LEFT-WALL### 1 conclusions/significance 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 35 . 2 : 3 results 2 : 4 suggest 2 : 9 , 3 results 4 suggest 4 suggest 8 load 5 that 8 load 6 cumulative 8 load 7 inflammatory 8 load 9 , 23 tnf 9 , 28 associated 10 as 11 indexed 10 as 23 tnf 12 by 14 combination 12 by 20 - 12 by 23 tnf 13 the 14 combination 14 combination 15 of 14 combination 18 of 15 of 17 levels 16 high 17 levels 18 of 19 il 21 6 22 and 22 and 23 tnf 23 tnf 25 α 23 tnf 27 is 24 - 25 α 25 α 26 , 27 is 28 associated 28 associated 29 with 28 associated 32 for 29 with 31 odds 30 increased 31 odds 32 for 34 ltl 33 short 34 ltl in contrast , high levels of crp were not accompanied by short ltl in this cohort of older adults . 0 ###LEFT-WALL### 5 levels 0 ###LEFT-WALL### 8 were 0 ###LEFT-WALL### 20 . 1 in 2 contrast 1 in 3 , 1 in 5 levels 4 high 5 levels 5 levels 6 of 5 levels 8 were 6 of 7 crp 8 were 9 not 8 were 11 by 8 were 14 in 9 not 10 accompanied 11 by 13 ltl 12 short 13 ltl 14 in 16 cohort 15 this 16 cohort 16 cohort 17 of 17 of 19 adults 18 older 19 adults these data provide the first large - scale demonstration of links between inflammatory markers and ltl in an older population . 0 ###LEFT-WALL### 2 data 0 ###LEFT-WALL### 3 provide 0 ###LEFT-WALL### 21 . 1 these 2 data 2 data 3 provide 3 provide 9 demonstration 3 provide 12 between 3 provide 17 in 4 the 5 first 4 the 9 demonstration 6 large 7 - 6 large 8 scale 8 scale 9 demonstration 9 demonstration 10 of 10 of 11 links 12 between 15 and 13 inflammatory 14 markers 14 markers 15 and 15 and 16 ltl 17 in 20 population 18 an 20 population 19 older 20 population aging is thought to negatively affect multiple cellular processes including the ability to maintain chromosome stability . 0 ###LEFT-WALL### 1 aging 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 17 . 1 aging 2 is 2 is 3 thought 3 thought 4 to 3 thought 10 including 4 to 6 affect 5 negatively 6 affect 6 affect 9 processes 7 multiple 9 processes 8 cellular 9 processes 9 processes 10 including 10 including 12 ability 11 the 12 ability 12 ability 13 to 12 ability 14 maintain 13 to 14 maintain 14 maintain 16 stability 15 chromosome 16 stability chromosome instability ( cin ) is a common property of cancer cells and may be a contributing factor to cellular transformation . 0 ###LEFT-WALL### 2 instability 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 22 . 1 chromosome 2 instability 2 instability 4 cin 2 instability 13 and 3 ( 4 cin 4 cin 5 ) 6 is 9 property 6 is 13 and 7 a 8 common 7 a 9 property 8 common 9 property 9 property 10 of 10 of 12 cells 11 cancer 12 cells 13 and 14 may 13 and 19 to 14 may 15 be 15 be 18 factor 16 a 18 factor 17 contributing 18 factor 19 to 21 transformation 20 cellular 21 transformation the types of dna aberrations that arise during aging before tumor development and that contribute to tumorigenesis are currently unclear . 0 ###LEFT-WALL### 5 aberrations 0 ###LEFT-WALL### 18 are 0 ###LEFT-WALL### 21 . 1 the 2 types 2 types 3 of 2 types 5 aberrations 3 of 5 aberrations 4 dna 5 aberrations 5 aberrations 6 that 5 aberrations 7 arise 5 aberrations 18 are 6 that 7 arise 7 arise 8 during 7 arise 10 before 8 during 9 aging 10 before 13 and 10 before 15 contribute 11 tumor 12 development 12 development 13 and 13 and 14 that 13 and 15 contribute 15 contribute 16 to 16 to 17 tumorigenesis 18 are 19 currently 18 are 20 unclear mdm2 , a key regulator of the p53 tumor suppressor and modulator of dna break repair , is frequently overexpressed in malignancies and contributes to cin . 0 ###LEFT-WALL### 1 mdm2 0 ###LEFT-WALL### 23 and 0 ###LEFT-WALL### 27 . 1 mdm2 5 regulator 1 mdm2 23 and 2 , 5 regulator 3 a 5 regulator 4 key 5 regulator 5 regulator 6 of 5 regulator 13 of 5 regulator 17 , 6 of 11 and 7 the 10 suppressor 8 p53 10 suppressor 9 tumor 10 suppressor 10 suppressor 11 and 11 and 12 modulator 13 of 16 repair 14 dna 16 repair 15 break 16 repair 18 is 20 overexpressed 18 is 23 and 19 frequently 20 overexpressed 20 overexpressed 21 in 21 in 22 malignancies 23 and 24 contributes 23 and 25 to 25 to 26 cin to determine the relationship between aging and cin and the role of mdm2 , precancerous wild - type c57bl/6 and littermate - matched mdm2 transgenic mice at various ages were evaluated . 0 ###LEFT-WALL### 1 to 0 ###LEFT-WALL### 32 . 1 to 2 determine 2 determine 9 and 3 the 4 relationship 4 relationship 5 between 4 relationship 7 and 5 between 6 aging 7 and 8 cin 7 and 9 and 9 and 11 role 9 and 12 of 10 the 11 role 12 of 20 and 13 mdm2 14 , 14 , 19 c57bl/6 14 , 20 and 15 precancerous 18 type 16 wild 17 - 16 wild 18 type 18 type 19 c57bl/6 20 and 21 littermate 20 and 22 - 20 and 23 matched 20 and 24 mdm2 20 and 31 evaluated 24 mdm2 26 mice 24 mdm2 30 were 24 mdm2 31 evaluated 25 transgenic 26 mice 26 mice 27 at 26 mice 30 were 27 at 29 ages 28 various 29 ages metaphase analyses of wild - type cells showed a direct correlation between age and increased chromosome and chromatid breaks , chromosome fusions and aneuploidy , but the frequency of polyploidy remained stable over time . 0 ###LEFT-WALL### 2 analyses 0 ###LEFT-WALL### 8 showed 0 ###LEFT-WALL### 26 but 0 ###LEFT-WALL### 35 . 1 metaphase 2 analyses 2 analyses 3 of 2 analyses 8 showed 3 of 7 cells 4 wild 5 - 4 wild 6 type 6 type 7 cells 8 showed 11 correlation 8 showed 12 between 9 a 11 correlation 10 direct 11 correlation 12 between 23 and 13 age 14 and 14 and 16 chromosome 14 and 17 and 15 increased 16 chromosome 17 and 19 breaks 17 and 20 , 18 chromatid 19 breaks 20 , 22 fusions 20 , 23 and 21 chromosome 22 fusions 23 and 24 aneuploidy 25 , 26 but 26 but 28 frequency 26 but 31 remained 27 the 28 frequency 28 frequency 29 of 28 frequency 31 remained 29 of 30 polyploidy 31 remained 32 stable 32 stable 33 over 33 over 34 time elevated levels of mdm2 in precancerous mice increased both the numerical and the structural chromosomal abnormalities observed . 0 ###LEFT-WALL### 2 levels 0 ###LEFT-WALL### 8 increased 0 ###LEFT-WALL### 17 observed 1 elevated 2 levels 2 levels 3 of 2 levels 5 in 2 levels 8 increased 3 of 4 mdm2 5 in 7 mice 6 precancerous 7 mice 9 both 12 and 10 the 11 numerical 11 numerical 12 and 12 and 16 abnormalities 12 and 17 observed 13 the 16 abnormalities 14 structural 16 abnormalities 15 chromosomal 16 abnormalities 17 observed 18 . chromosome and chromatid breaks , chromosome fusions , aneuploidy and polyploidy were increased in older mdm2 transgenic mice compared with wild - type littermates . 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 13 increased 0 ###LEFT-WALL### 25 . 1 chromosome 2 and 2 and 4 breaks 2 and 5 , 3 chromatid 4 breaks 5 , 7 fusions 5 , 8 , 6 chromosome 7 fusions 8 , 9 aneuploidy 8 , 10 and 10 and 11 polyploidy 10 and 12 were 12 were 13 increased 13 increased 14 in 13 increased 20 with 14 in 16 mdm2 15 older 16 mdm2 16 mdm2 18 mice 16 mdm2 19 compared 17 transgenic 18 mice 18 mice 19 compared 20 with 24 littermates 21 wild 22 - 21 wild 24 littermates 23 type 24 littermates unexpectedly , chromosome fusions , aneuploidy and polyploidy rates in mdm2 transgenic mice , but not chromosome and chromatid breaks , showed cooperation between mdm2 overexpression and age . 0 ###LEFT-WALL### 18 and 0 ###LEFT-WALL### 21 , 0 ###LEFT-WALL### 29 . 1 unexpectedly 2 , 1 unexpectedly 18 and 3 chromosome 4 fusions 4 fusions 5 , 5 , 17 chromosome 5 , 18 and 6 aneuploidy 7 and 7 and 9 rates 7 and 14 , 7 and 15 but 7 and 17 chromosome 8 polyploidy 9 rates 9 rates 10 in 10 in 13 mice 11 mdm2 13 mice 12 transgenic 13 mice 15 but 16 not 18 and 19 chromatid 18 and 21 , 20 breaks 21 , 21 , 22 showed 22 showed 23 cooperation 22 showed 26 overexpression 22 showed 27 and 23 cooperation 24 between 24 between 25 mdm2 27 and 28 age notably , mdm2 overexpression promoted gains in one or more chromosomes with age , while it did not affect the rate of chromosome loss . 0 ###LEFT-WALL### 4 overexpression 0 ###LEFT-WALL### 6 gains 1 notably 2 , 1 notably 4 overexpression 3 mdm2 4 overexpression 4 overexpression 5 promoted 4 overexpression 6 gains 6 gains 7 in 6 gains 12 with 6 gains 15 while 7 in 9 or 8 one 9 or 9 or 11 chromosomes 10 more 11 chromosomes 12 with 13 age 14 , 15 while 15 while 16 it 15 while 19 affect 15 while 25 . 16 it 17 did 17 did 18 not 17 did 19 affect 19 affect 21 rate 20 the 21 rate 21 rate 22 of 22 of 24 loss 23 chromosome 24 loss therefore , aging increased specific forms of genomic instability , and elevated mdm2 expression cooperated with aging to increase the likelihood of gaining certain chromosomal abnormalities of the kind thought to lead to cancer development . 0 ###LEFT-WALL### 3 aging 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 36 . 1 therefore 2 , 1 therefore 3 aging 3 aging 11 and 4 increased 6 forms 4 increased 11 and 5 specific 6 forms 6 forms 7 of 7 of 9 instability 8 genomic 9 instability 10 , 11 and 11 and 12 elevated 12 elevated 13 mdm2 12 elevated 18 to 13 mdm2 14 expression 13 mdm2 17 aging 14 expression 15 cooperated 15 cooperated 16 with 16 with 17 aging 18 to 19 increase 19 increase 21 likelihood 20 the 21 likelihood 21 likelihood 22 of 21 likelihood 27 of 21 likelihood 33 to 22 of 23 gaining 23 gaining 26 abnormalities 24 certain 26 abnormalities 25 chromosomal 26 abnormalities 27 of 30 thought 28 the 30 thought 29 kind 30 thought 30 thought 31 to 30 thought 32 lead 31 to 32 lead 33 to 35 development 34 cancer 35 development purpose : to investigate longitudinal changes in anterior chamber depth ( acd ) and anterior chamber angle ( aca ) and the associated factors in patients with primary open - angle glaucoma using the scanning peripheral acd analyzer . 0 ###LEFT-WALL### 1 purpose 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 39 . 2 : 3 to 2 : 4 investigate 2 : 21 and 3 to 4 investigate 4 investigate 14 and 5 longitudinal 6 changes 6 changes 7 in 6 changes 14 and 7 in 10 depth 8 anterior 9 chamber 9 chamber 10 depth 10 depth 12 acd 11 ( 12 acd 12 acd 13 ) 14 and 17 angle 14 and 19 aca 15 anterior 16 chamber 16 chamber 17 angle 18 ( 19 aca 19 aca 20 ) 21 and 24 factors 21 and 38 analyzer 22 the 24 factors 23 associated 24 factors 24 factors 25 in 24 factors 38 analyzer 25 in 26 patients 26 patients 27 with 27 with 32 glaucoma 28 primary 31 angle 29 open 30 - 29 open 31 angle 31 angle 32 glaucoma 32 glaucoma 33 using 33 using 37 acd 34 the 37 acd 35 scanning 37 acd 36 peripheral 37 acd methods : the scanning peripheral acd analyzer evaluated acd by numeric grade ( acdg 1 to 12 ) and aca twice in 2003 and 2008 . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 26 . 2 : 7 analyzer 2 : 8 evaluated 3 the 7 analyzer 4 scanning 7 analyzer 5 peripheral 7 analyzer 6 acd 7 analyzer 7 analyzer 8 evaluated 8 evaluated 19 and 8 evaluated 21 twice 8 evaluated 22 in 9 acd 10 by 9 acd 19 and 10 by 12 grade 11 numeric 12 grade 12 grade 14 acdg 13 ( 14 acdg 14 acdg 15 1 14 acdg 16 to 14 acdg 18 ) 16 to 17 12 19 and 20 aca 22 in 24 and 23 2003 24 and 24 and 25 2008 the exclusion criteria were [as] follows : history of laser [or] incisional surgery , other ocular diseases that may affect visual field [,] visual acuity less than 20/30 , and treatment with pilocarpine ophthalmic solution . 0 ###LEFT-WALL### 2 exclusion 0 ###LEFT-WALL### 6 follows 0 ###LEFT-WALL### 7 : 0 ###LEFT-WALL### 36 . 1 the 2 exclusion 2 exclusion 3 criteria 2 exclusion 4 were 2 exclusion 6 follows 3 criteria 4 were 7 : 35 solution 8 history 9 of 8 history 30 and 9 of 13 surgery 10 laser 13 surgery 12 incisional 13 surgery 13 surgery 17 diseases 14 , 17 diseases 15 other 17 diseases 16 ocular 17 diseases 17 diseases 18 that 17 diseases 19 may 17 diseases 29 , 18 that 19 may 19 may 20 affect 20 affect 25 acuity 20 affect 26 less 20 affect 27 than 21 visual 22 field 22 field 25 acuity 24 visual 25 acuity 27 than 28 20/30 30 and 31 treatment 30 and 32 with 30 and 35 solution 32 with 33 pilocarpine 34 ophthalmic 35 solution patients [with] [pseudophakic] [eye] were used as control . 0 ###LEFT-WALL### 1 patients 0 ###LEFT-WALL### 6 used 0 ###LEFT-WALL### 9 . 1 patients 5 were 5 were 6 used 6 used 7 as 7 as 8 control results : one hundred fifty - seven patients with glaucoma and 26 patients [with] pseudophakic eye were subjected to the analysis . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 6 - 1 results 2 : 2 : 5 fifty 3 one 4 hundred 4 hundred 5 fifty 6 - 8 patients 6 - 18 subjected 6 - 22 . 7 seven 8 patients 8 patients 9 with 8 patients 17 were 9 with 11 and 10 glaucoma 11 and 11 and 16 eye 12 26 16 eye 13 patients 16 eye 15 pseudophakic 16 eye 17 were 18 subjected 18 subjected 19 to 19 to 21 analysis 20 the 21 analysis acdg and aca of patients with glaucoma were significantly decreased from 7.2±2.3 to 6.5±2.1 ( p<0.001 ) and from 34.2±12.6 to 28.1±10.3 degrees ( p<0.0001 ) , respectively , whereas patients with cataract surgery showed no significant changes in acdg and aca . 0 ###LEFT-WALL### 22 28.1±10.3 1 acdg 2 and 2 and 3 aca 2 and 8 were 3 aca 4 of 4 of 5 patients 5 patients 6 with 6 with 7 glaucoma 8 were 10 decreased 9 significantly 10 decreased 10 decreased 11 from 10 decreased 21 to 11 from 12 7.2±2.3 12 7.2±2.3 18 and 13 to 14 6.5±2.1 13 to 18 and 14 6.5±2.1 16 p<0.001 15 ( 16 p<0.001 16 p<0.001 17 ) 18 and 19 from 19 from 20 34.2±12.6 21 to 22 28.1±10.3 22 28.1±10.3 23 degrees 22 28.1±10.3 28 respectively 22 28.1±10.3 30 whereas 22 28.1±10.3 39 in 23 degrees 25 p<0.0001 24 ( 25 p<0.0001 25 p<0.0001 26 ) 27 , 28 respectively 28 respectively 29 , 30 whereas 31 patients 30 whereas 35 showed 31 patients 32 with 31 patients 35 showed 32 with 34 surgery 33 cataract 34 surgery 35 showed 38 changes 36 no 38 changes 37 significant 38 changes 39 in 42 aca 40 acdg 41 and 41 and 42 aca 42 aca 43 . the change in acd was greater at the peripheral region than at the central region . 0 ###LEFT-WALL### 2 change 0 ###LEFT-WALL### 5 was 0 ###LEFT-WALL### 16 . 1 the 2 change 2 change 3 in 2 change 5 was 3 in 4 acd 5 was 6 greater 6 greater 7 at 6 greater 11 than 7 at 10 region 8 the 10 region 9 peripheral 10 region 11 than 12 at 12 at 15 region 13 the 15 region 14 central 15 region the decrease in acdg was significantly associated with deep initial acdg and wide aca . 0 ###LEFT-WALL### 2 decrease 0 ###LEFT-WALL### 7 associated 0 ###LEFT-WALL### 15 . 1 the 2 decrease 2 decrease 3 in 2 decrease 5 was 3 in 4 acdg 5 was 6 significantly 5 was 7 associated 7 associated 8 with 8 with 12 and 9 deep 10 initial 10 initial 11 acdg 11 acdg 12 and 12 and 14 aca 13 wide 14 aca patients having shallow acdg and narrow aca showed more rapid deterioration of visual [field] than those having deep acdg and wide aca . 0 ###LEFT-WALL### 5 and 0 ###LEFT-WALL### 8 showed 0 ###LEFT-WALL### 23 . 1 patients 2 having 1 patients 5 and 2 having 4 acdg 3 shallow 4 acdg 5 and 7 aca 5 and 8 showed 6 narrow 7 aca 8 showed 11 deterioration 9 more 11 deterioration 10 rapid 11 deterioration 11 deterioration 12 of 12 of 22 aca 13 visual 15 than 13 visual 20 and 15 than 16 those 16 those 17 having 17 having 18 deep 17 having 19 acdg 20 and 21 wide 20 and 22 aca conclusions : acdg and aca decreased with age , and initial acdg and aca were related to the progression of open - angle glaucoma . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 13 and 2 : 16 related 2 : 25 . 3 acdg 4 and 4 and 5 aca 4 and 6 decreased 4 and 10 and 6 decreased 7 with 7 with 8 age 9 , 10 and 10 and 12 acdg 10 and 13 and 11 initial 12 acdg 13 and 14 aca 13 and 15 were 15 were 16 related 16 related 17 to 17 to 19 progression 18 the 19 progression 19 progression 20 of 20 of 24 glaucoma 21 open 22 - 21 open 24 glaucoma 23 angle 24 glaucoma objective : adipocyte infiltration of the musculoskeletal system is well recognized as a hallmark of aging , obesity , and type 2 diabetes . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 11 recognized 0 ###LEFT-WALL### 24 . 1 objective 2 : 2 : 3 adipocyte 3 adipocyte 4 infiltration 3 adipocyte 9 is 4 infiltration 5 of 4 infiltration 9 is 5 of 8 system 6 the 8 system 7 musculoskeletal 8 system 10 well 11 recognized 11 recognized 12 as 12 as 20 and 13 a 14 hallmark 14 hallmark 15 of 14 hallmark 17 , 15 of 16 aging 17 , 18 obesity 17 , 20 and 19 , 20 and 20 and 23 diabetes 21 type 23 diabetes 22 2 23 diabetes intermuscular adipocytes might serve as a benign storage site [for] surplus lipid or play a role in disrupting energy homeostasis as a result of dysregulated lipolysis or secretion of proinflammatory cytokines . 0 ###LEFT-WALL### 2 adipocytes 0 ###LEFT-WALL### 13 or 0 ###LEFT-WALL### 32 . 1 intermuscular 2 adipocytes 2 adipocytes 3 might 3 might 13 or 4 serve 5 as 4 serve 13 or 5 as 12 lipid 6 a 12 lipid 7 benign 8 storage 8 storage 9 site 9 site 12 lipid 11 surplus 12 lipid 13 or 14 play 13 or 21 as 14 play 16 role 14 play 17 in 15 a 16 role 17 in 18 disrupting 18 disrupting 20 homeostasis 19 energy 20 homeostasis 21 as 23 result 22 a 23 result 23 result 24 of 23 result 29 of 24 of 27 or 25 dysregulated 26 lipolysis 26 lipolysis 27 or 27 or 28 secretion 29 of 31 cytokines 30 proinflammatory 31 cytokines this investigation sought to understand the net impact of local adipocytes on skeletal myocyte metabolism . 0 ###LEFT-WALL### 2 investigation 0 ###LEFT-WALL### 3 sought 0 ###LEFT-WALL### 16 . 1 this 2 investigation 2 investigation 3 sought 3 sought 4 to 3 sought 5 understand 4 to 5 understand 5 understand 8 impact 5 understand 12 on 6 the 8 impact 7 net 8 impact 8 impact 9 of 9 of 11 adipocytes 10 local 11 adipocytes 12 on 15 metabolism 13 skeletal 15 metabolism 14 myocyte 15 metabolism research design and methods : interactions between these two tissues were modeled using a [coculture] system composed of primary human adipocytes and human skeletal myotubes derived from lean or obese donors . 0 ###LEFT-WALL### 4 methods 0 ###LEFT-WALL### 5 : 0 ###LEFT-WALL### 32 . 1 research 2 design 2 design 3 and 3 and 4 methods 5 : 22 and 6 interactions 7 between 6 interactions 12 modeled 6 interactions 18 of 6 interactions 22 and 7 between 9 two 8 these 9 two 9 two 10 tissues 9 two 11 were 10 tissues 11 were 12 modeled 13 using 12 modeled 17 composed 13 using 16 system 14 a 16 system 18 of 21 adipocytes 19 primary 21 adipocytes 20 human 21 adipocytes 22 and 25 myotubes 22 and 27 from 23 human 25 myotubes 24 skeletal 25 myotubes 25 myotubes 26 derived 27 from 29 or 28 lean 29 or 29 or 31 donors 30 obese 31 donors metabolic analysis of myocytes was performed [after] [coculture] [with] lipolytically silent or activated adipocytes and included transcript and metabolite profiling along with assessment of substrate selection and insulin action . 0 ###LEFT-WALL### 2 analysis 0 ###LEFT-WALL### 12 or 0 ###LEFT-WALL### 30 . 1 metabolic 2 analysis 2 analysis 3 of 2 analysis 12 or 3 of 4 myocytes 5 was 6 performed 5 was 12 or 6 performed 10 lipolytically 6 performed 11 silent 12 or 13 activated 12 or 18 and 14 adipocytes 15 and 15 and 17 transcript 15 and 18 and 16 included 17 transcript 18 and 19 metabolite 18 and 20 profiling 20 profiling 22 with 20 profiling 29 action 21 along 22 with 22 with 27 and 23 assessment 24 of 23 assessment 27 and 24 of 26 selection 25 substrate 26 selection 27 and 28 insulin results : cocultured adipocytes increased myotube mrna expression of genes involved in oxidative metabolism , regardless of the donor and degree of lipolytic activity . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 4 adipocytes 2 : 6 myotube 3 cocultured 4 adipocytes 4 adipocytes 5 increased 4 adipocytes 6 myotube 6 myotube 8 expression 7 mrna 8 expression 8 expression 9 of 9 of 10 genes 10 genes 11 involved 11 involved 12 in 11 involved 17 of 12 in 14 metabolism 13 oxidative 14 metabolism 15 , 17 of 16 regardless 17 of 17 of 20 and 17 of 25 . 18 the 19 donor 19 donor 20 and 20 and 21 degree 20 and 22 of 22 of 24 activity 23 lipolytic 24 activity adipocytes in the basal state sequestered free fatty acids , thereby forcing neighboring myotubes to rely more heavily on glucose fuel . 0 ###LEFT-WALL### 1 adipocytes 0 ###LEFT-WALL### 6 sequestered 1 adipocytes 2 in 1 adipocytes 6 sequestered 2 in 5 state 3 the 5 state 4 basal 5 state 6 sequestered 9 acids 7 free 9 acids 8 fatty 9 acids 9 acids 12 forcing 10 , 12 forcing 11 thereby 12 forcing 12 forcing 14 myotubes 12 forcing 15 to 12 forcing 16 rely 12 forcing 22 . 13 neighboring 14 myotubes 15 to 16 rely 16 rely 18 heavily 16 rely 19 on 17 more 18 heavily 19 on 21 fuel 20 glucose 21 fuel under this condition , insulin action was enhanced in myotubes from lean but not obese donors . 0 ###LEFT-WALL### 6 action 0 ###LEFT-WALL### 8 enhanced 0 ###LEFT-WALL### 17 . 1 under 3 condition 1 under 4 , 1 under 6 action 2 this 3 condition 5 insulin 6 action 6 action 7 was 7 was 8 enhanced 8 enhanced 9 in 9 in 10 myotubes 10 myotubes 11 from 11 from 16 donors 12 lean 13 but 13 but 14 not 13 but 15 obese 13 but 16 donors 14 not 15 obese in contrast , when exposed to lipolytically active adipocytes , cocultured myotubes shifted substrate use in favor of fatty acids , which was accompanied by intracellular accumulation of triacylglycerol and even - chain acylcarnitines , decreased glucose oxidation , and modest attenuation of insulin signaling . 0 ###LEFT-WALL### 12 myotubes 0 ###LEFT-WALL### 13 shifted 0 ###LEFT-WALL### 35 , 0 ###LEFT-WALL### 46 . 1 in 2 contrast 1 in 3 , 1 in 12 myotubes 3 , 4 when 4 when 5 exposed 4 when 10 , 4 when 11 cocultured 5 exposed 6 to 6 to 9 adipocytes 7 lipolytically 8 active 8 active 9 adipocytes 11 cocultured 12 myotubes 12 myotubes 13 shifted 13 shifted 15 use 13 shifted 16 in 14 substrate 15 use 16 in 17 favor 17 favor 18 of 17 favor 22 which 18 of 20 acids 19 fatty 20 acids 21 , 22 which 22 which 23 was 22 which 35 , 23 was 24 accompanied 24 accompanied 25 by 25 by 34 acylcarnitines 26 intracellular 34 acylcarnitines 27 accumulation 28 of 27 accumulation 30 and 28 of 29 triacylglycerol 30 and 33 chain 30 and 34 acylcarnitines 31 even 32 - 31 even 33 chain 35 , 40 and 36 decreased 37 glucose 37 glucose 38 oxidation 38 oxidation 40 and 39 , 40 and 40 and 42 attenuation 40 and 43 of 40 and 45 signaling 41 modest 42 attenuation 43 of 44 insulin conclusions : the effects of cocultured adipocytes on myocyte substrate selection and insulin action depended on the metabolic state of the system . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 12 and 2 : 15 depended 2 : 23 . 3 the 4 effects 4 effects 5 of 4 effects 12 and 5 of 7 adipocytes 6 cocultured 7 adipocytes 7 adipocytes 8 on 8 on 11 selection 9 myocyte 11 selection 10 substrate 11 selection 12 and 14 action 12 and 15 depended 13 insulin 14 action 15 depended 16 on 16 on 19 state 17 the 19 state 18 metabolic 19 state 19 state 20 of 20 of 22 system 21 the 22 system these findings are relevant to understanding the metabolic consequences of intermuscular adipogenesis . 0 ###LEFT-WALL### 2 findings 0 ###LEFT-WALL### 3 are 0 ###LEFT-WALL### 13 . 1 these 2 findings 2 findings 3 are 3 are 4 relevant 4 relevant 5 to 5 to 6 understanding 6 understanding 9 consequences 7 the 9 consequences 8 metabolic 9 consequences 9 consequences 10 of 10 of 12 adipogenesis 11 intermuscular 12 adipogenesis there is accumulating evidence suggesting that children may drive the spread of influenza epidemics . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 15 . 1 there 2 is 2 is 4 evidence 3 accumulating 4 evidence 4 evidence 5 suggesting 5 suggesting 6 that 6 that 7 children 6 that 9 drive 7 children 8 may 8 may 9 drive 9 drive 11 spread 10 the 11 spread 11 spread 12 of 12 of 14 epidemics 13 influenza 14 epidemics the objective of this study was to quantify the lead time by age using laboratory [-] confirmed cases of influenza a for the 1995/1996 - 2005/2006 seasons from canadian communities and laboratory - confirmed hospital admissions for the h1n1/2009 pandemic strain . 0 ###LEFT-WALL### 2 objective 0 ###LEFT-WALL### 6 was 0 ###LEFT-WALL### 34 confirmed 0 ###LEFT-WALL### 42 . 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 11 time 7 to 8 quantify 8 quantify 10 lead 9 the 10 lead 11 time 12 by 12 by 13 age 13 age 14 using 13 age 19 of 14 using 18 cases 15 laboratory 17 confirmed 17 confirmed 18 cases 19 of 31 and 20 influenza 21 a 20 influenza 22 for 20 influenza 31 and 22 for 27 seasons 23 the 25 - 24 1995/1996 25 - 25 - 26 2005/2006 25 - 27 seasons 27 seasons 28 from 28 from 30 communities 29 canadian 30 communities 31 and 32 laboratory 33 - 34 confirmed 34 confirmed 36 admissions 34 confirmed 37 for 35 hospital 36 admissions 37 for 41 strain 38 the 41 strain 39 h1n1/2009 40 pandemic 40 pandemic 41 strain with alignment of the epidemic curves locally before aggregation of cases , slight age - specific differences in the timing of infection became apparent . 0 ###LEFT-WALL### 17 differences 0 ###LEFT-WALL### 23 became 0 ###LEFT-WALL### 25 . 1 with 2 alignment 1 with 17 differences 2 alignment 3 of 3 of 6 curves 4 the 6 curves 5 epidemic 6 curves 7 locally 17 differences 8 before 9 aggregation 8 before 15 - 8 before 17 differences 9 aggregation 10 of 10 of 11 cases 11 cases 14 age 12 , 14 age 13 slight 14 age 14 age 15 - 16 specific 17 differences 17 differences 18 in 17 differences 21 of 17 differences 23 became 18 in 20 timing 19 the 20 timing 21 of 22 infection 23 became 24 apparent for seasonal influenza , both the 10 - 19 - [and] 20 - 29 - year age groups peaked 1 week earlier than other age groups , while during the fall wave of the 2009 pandemic , infections peaked earlier among only [the] 10 - 19 - year age group . 0 ###LEFT-WALL### 18 groups 0 ###LEFT-WALL### 19 peaked 0 ###LEFT-WALL### 27 , 1 for 3 influenza 1 for 18 groups 2 seasonal 3 influenza 3 influenza 5 both 4 , 5 both 5 both 6 the 5 both 7 10 5 both 8 - 6 the 7 10 9 19 18 groups 10 - 13 - 12 20 13 - 13 - 14 29 13 - 15 - 13 - 18 groups 16 year 17 age 17 age 18 groups 18 groups 19 peaked 19 peaked 22 earlier 19 peaked 23 than 20 1 21 week 21 week 22 earlier 23 than 26 groups 24 other 26 groups 25 age 26 groups 27 , 38 infections 27 , 39 peaked 27 , 45 - 28 while 29 during 28 while 38 infections 29 during 32 wave 30 the 32 wave 31 fall 32 wave 32 wave 33 of 33 of 35 2009 34 the 35 2009 36 pandemic 37 , 36 pandemic 38 infections 38 infections 39 peaked 39 peaked 40 earlier 39 peaked 41 among 41 among 44 10 42 only 44 10 45 - 46 19 45 - 47 - 47 - 50 group 47 - 51 . 48 year 50 group 49 age 50 group this analysis casts doubt on the hypothesis that younger school [-] age children actually lead influenza epidemic waves . 0 ###LEFT-WALL### 2 analysis 0 ###LEFT-WALL### 3 casts 0 ###LEFT-WALL### 19 . 1 this 2 analysis 2 analysis 3 casts 3 casts 4 doubt 3 casts 5 on 5 on 7 hypothesis 6 the 7 hypothesis 7 hypothesis 8 that 8 that 13 children 8 that 15 lead 9 younger 10 school 10 school 13 children 12 age 13 children 13 children 15 lead 14 actually 15 lead 15 lead 18 waves 16 influenza 18 waves 17 epidemic 18 waves heat is the most abundant byproduct of cellular metabolism . 0 ###LEFT-WALL### 1 heat 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 10 . 1 heat 2 is 2 is 6 byproduct 3 the 6 byproduct 4 most 5 abundant 5 abundant 6 byproduct 6 byproduct 7 of 7 of 9 metabolism 8 cellular 9 metabolism as such [,] dynamic exercise in which a significant percentage of muscle [mass] is engaged generates thermoregulatory demands that are met in part by increases in skin blood flow . 0 ###LEFT-WALL### 18 demands 0 ###LEFT-WALL### 28 blood 0 ###LEFT-WALL### 30 . 1 as 5 exercise 1 as 16 generates 1 as 18 demands 2 such 5 exercise 4 dynamic 5 exercise 5 exercise 6 in 5 exercise 16 generates 6 in 7 which 6 in 10 percentage 6 in 15 engaged 8 a 10 percentage 9 significant 10 percentage 10 percentage 11 of 10 percentage 14 is 11 of 12 muscle 14 is 15 engaged 16 generates 17 thermoregulatory 18 demands 19 that 18 demands 20 are 18 demands 28 blood 19 that 20 are 20 are 21 met 21 met 23 part 21 met 26 in 22 in 23 part 23 part 24 by 24 by 25 increases 26 in 27 skin 28 blood 29 flow increased skin blood flow during exercise adds to the demands on cardiac output and confers additional circulatory strain beyond that associated with perfusion of active muscle alone . 0 ###LEFT-WALL### 4 flow 0 ###LEFT-WALL### 21 associated 0 ###LEFT-WALL### 28 . 1 increased 2 skin 2 skin 4 flow 3 blood 4 flow 4 flow 5 during 4 flow 14 and 4 flow 21 associated 5 during 6 exercise 7 adds 8 to 7 adds 11 on 7 adds 14 and 8 to 10 demands 9 the 10 demands 11 on 13 output 12 cardiac 13 output 14 and 15 confers 14 and 18 strain 14 and 19 beyond 16 additional 18 strain 17 circulatory 18 strain 19 beyond 20 that 21 associated 22 with 21 associated 27 alone 22 with 23 perfusion 23 perfusion 24 of 24 of 26 muscle 25 active 26 muscle endurance exercise training results in a number of physiological adaptations which ultimately reduce circulatory strain and shift thermoregulatory control of skin blood flow to higher levels of blood flow for a given core temperature . 0 ###LEFT-WALL### 3 training 0 ###LEFT-WALL### 4 results 0 ###LEFT-WALL### 35 . 1 endurance 2 exercise 2 exercise 3 training 3 training 4 results 4 results 5 in 5 in 16 and 6 a 7 number 7 number 8 of 7 number 16 and 8 of 10 adaptations 9 physiological 10 adaptations 10 adaptations 11 which 10 adaptations 13 reduce 11 which 13 reduce 12 ultimately 13 reduce 13 reduce 15 strain 14 circulatory 15 strain 16 and 19 control 16 and 20 of 16 and 24 to 16 and 27 of 17 shift 19 control 18 thermoregulatory 19 control 20 of 23 flow 21 skin 22 blood 22 blood 23 flow 24 to 26 levels 25 higher 26 levels 27 of 29 flow 28 blood 29 flow 29 flow 30 for 30 for 34 temperature 31 a 34 temperature 32 given 33 core 33 core 34 temperature in addition , exercise training induces peripheral vascular adaptations within the cutaneous microvasculature indicative [of] enhanced endothelium - dependent vasomotor function . 0 ###LEFT-WALL### 5 training 0 ###LEFT-WALL### 6 induces 0 ###LEFT-WALL### 18 - 0 ###LEFT-WALL### 22 . 1 in 2 addition 1 in 3 , 1 in 5 training 4 exercise 5 training 5 training 6 induces 6 induces 9 adaptations 6 induces 10 within 7 peripheral 9 adaptations 8 vascular 9 adaptations 10 within 17 endothelium 11 the 17 endothelium 12 cutaneous 17 endothelium 13 microvasculature 17 endothelium 14 indicative 17 endothelium 16 enhanced 17 endothelium 18 - 21 function 19 dependent 21 function 20 vasomotor 21 function however , it is not currently clear how ( or [if] ) these local vascular adaptations contribute to the beneficial changes in thermoregulatory control of skin blood flow following exercise training . 0 ###LEFT-WALL### 3 it 0 ###LEFT-WALL### 4 is 0 ###LEFT-WALL### 10 or 0 ###LEFT-WALL### 32 . 1 however 2 , 1 however 3 it 3 it 4 is 4 is 5 not 4 is 6 currently 4 is 7 clear 5 not 6 currently 7 clear 8 how 9 ( 10 or 10 or 12 ) 10 or 16 adaptations 10 or 17 contribute 13 these 16 adaptations 14 local 16 adaptations 15 vascular 16 adaptations 16 adaptations 17 contribute 17 contribute 18 to 18 to 21 changes 19 the 21 changes 20 beneficial 21 changes 21 changes 22 in 21 changes 25 of 21 changes 29 following 22 in 24 control 23 thermoregulatory 24 control 25 of 28 flow 26 skin 28 flow 27 blood 28 flow 29 following 31 training 30 exercise 31 training the purpose of this hot topic review is to synthesize the literature pertaining to exercise training - mediated changes in cutaneous microvascular reactivity and thermoregulatory control of skin blood flow . 0 ###LEFT-WALL### 2 purpose 0 ###LEFT-WALL### 15 exercise 0 ###LEFT-WALL### 17 - 0 ###LEFT-WALL### 31 . 1 the 2 purpose 2 purpose 3 of 2 purpose 8 is 3 of 7 review 4 this 7 review 5 hot 6 topic 6 topic 7 review 8 is 9 to 8 is 10 synthesize 9 to 10 synthesize 10 synthesize 12 literature 10 synthesize 14 to 11 the 12 literature 12 literature 13 pertaining 14 to 15 exercise 15 exercise 16 training 17 - 24 and 17 - 30 flow 18 mediated 19 changes 19 changes 20 in 19 changes 24 and 20 in 23 reactivity 21 cutaneous 23 reactivity 22 microvascular 23 reactivity 24 and 26 control 24 and 27 of 24 and 30 flow 25 thermoregulatory 26 control 27 of 29 blood 28 skin 29 blood in addition , we address mechanisms driving changes in cutaneous microvascular reactivity and thermoregulatory control of skin blood flow , and pose the question : [what] ( if any [ )(is the functional role of increased cutaneous microvascular reactivity following exercise training ? 0 ###LEFT-WALL### 4 we 0 ###LEFT-WALL### 5 address 1 in 2 addition 1 in 3 , 1 in 4 we 4 we 5 address 5 address 6 mechanisms 5 address 9 in 5 address 28 if 6 mechanisms 7 driving 7 driving 8 changes 9 in 13 and 10 cutaneous 12 reactivity 11 microvascular 12 reactivity 12 reactivity 13 and 13 and 15 control 13 and 16 of 13 and 24 question 13 and 25 : 14 thermoregulatory 15 control 16 of 21 and 17 skin 19 flow 18 blood 19 flow 19 flow 21 and 20 , 21 and 21 and 22 pose 23 the 24 question 24 question 25 : 27 ( 28 if 28 if 29 any 28 if 31 )(is 28 if 43 ? 29 any 31 )(is 31 )(is 34 role 32 the 34 role 33 functional 34 role 34 role 35 of 35 of 42 training 36 increased 42 training 37 cutaneous 39 reactivity 38 microvascular 39 reactivity 39 reactivity 40 following 40 following 42 training 41 exercise 42 training objective : this study examines the relationship between increasing certified nursing assistants ( cnas ) and licensed nurse staffing ratios and deficiencies in florida nursing homes over a 4 [-] year period . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 2 : 21 and 2 : 33 . 3 this 4 study 4 study 16 and 4 study 21 and 5 examines 7 relationship 5 examines 8 between 5 examines 16 and 6 the 7 relationship 8 between 9 increasing 9 increasing 12 assistants 10 certified 11 nursing 11 nursing 12 assistants 12 assistants 14 cnas 13 ( 14 cnas 14 cnas 15 ) 16 and 17 licensed 16 and 20 ratios 18 nurse 20 ratios 19 staffing 20 ratios 21 and 22 deficiencies 21 and 23 in 21 and 25 nursing 23 in 24 florida 25 nursing 26 homes 25 nursing 27 over 27 over 32 period 28 a 32 period 29 4 32 period 31 year 32 period methods : data from florida staffing reports and the online survey certification and reporting database examine the relationship among staffing levels and deficiency citations for 663 florida nursing homes between 2002 and 2005 . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 34 . 1 methods 2 : 2 : 3 data 3 data 4 from 3 data 6 staffing 3 data 19 among 4 from 5 florida 6 staffing 8 and 7 reports 8 and 8 and 10 online 8 and 13 and 8 and 16 examine 9 the 10 online 11 survey 12 certification 12 certification 13 and 13 and 15 database 13 and 16 examine 14 reporting 15 database 16 examine 18 relationship 17 the 18 relationship 19 among 20 staffing 20 staffing 24 citations 20 staffing 30 between 21 levels 22 and 22 and 23 deficiency 22 and 24 citations 24 citations 25 for 24 citations 28 nursing 25 for 27 florida 26 663 27 florida 28 nursing 29 homes 30 between 32 and 31 2002 32 and 32 and 33 2005 using a generalized estimating equation approach in sas proc genmod , we estimate the relationship between cna and licensed nursing staff , and facilities ' total deficiency score and quality of care deficiency scores - calculated using the centers for medicare and medicaid services ' nursing home compare five - star quality rating system , which accounts for the complexity of the scope and severity of the cittions . 0 ###LEFT-WALL### 12 we 0 ###LEFT-WALL### 13 estimate 0 ###LEFT-WALL### 36 calculated 0 ###LEFT-WALL### 50 - 0 ###LEFT-WALL### 69 . 1 using 6 approach 1 using 11 , 1 using 12 we 2 a 6 approach 3 generalized 5 equation 4 estimating 5 equation 5 equation 6 approach 6 approach 7 in 7 in 10 genmod 8 sas 9 proc 9 proc 10 genmod 12 we 13 estimate 13 estimate 33 deficiency 13 estimate 34 scores 14 the 15 relationship 15 relationship 16 between 15 relationship 18 and 16 between 17 cna 18 and 21 staff 18 and 22 , 18 and 23 and 19 licensed 20 nursing 20 nursing 21 staff 22 , 23 and 23 and 28 score 23 and 29 and 24 facilities 25 ' 25 ' 28 score 26 total 27 deficiency 27 deficiency 28 score 29 and 30 quality 29 and 31 of 29 and 33 deficiency 31 of 32 care 33 deficiency 34 scores 35 - 36 calculated 36 calculated 37 using 37 using 49 five 38 the 44 services 39 centers 40 for 39 centers 44 services 40 for 43 medicaid 41 medicare 42 and 42 and 43 medicaid 44 services 45 ' 45 ' 49 five 46 nursing 47 home 47 home 48 compare 48 compare 49 five 50 - 54 system 50 - 55 , 51 star 52 quality 52 quality 53 rating 53 rating 54 system 55 , 56 which 55 , 57 accounts 56 which 57 accounts 57 accounts 58 for 58 for 60 complexity 59 the 60 complexity 60 complexity 61 of 60 complexity 66 of 61 of 64 and 62 the 63 scope 63 scope 64 and 64 and 65 severity 66 of 68 cittions 67 the 68 cittions results : our results confirmed that higher cna staffing levels were predictors of lower total deficiency scores and quality of care deficiency scores after controlling for facility characteristics . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 29 . 2 : 4 results 2 : 5 confirmed 2 : 18 and 3 our 4 results 4 results 5 confirmed 5 confirmed 6 that 6 that 8 cna 6 that 11 were 7 higher 8 cna 8 cna 9 staffing 8 cna 11 were 9 staffing 10 levels 11 were 12 predictors 12 predictors 13 of 13 of 17 scores 14 lower 17 scores 15 total 16 deficiency 16 deficiency 17 scores 18 and 19 quality 18 and 23 scores 19 quality 20 of 19 quality 23 scores 20 of 22 deficiency 21 care 22 deficiency 23 scores 24 after 24 after 25 controlling 25 controlling 26 for 25 controlling 28 characteristics 26 for 27 facility conclusion : with a large sample size , repeated measure design , and advanced methods , we have found a relationship between cna staffing and nursing home quality . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 9 repeated 0 ###LEFT-WALL### 29 . 1 conclusion 2 : 2 : 3 with 3 with 7 size 4 a 5 large 4 a 7 size 5 large 6 sample 6 sample 7 size 8 , 9 repeated 9 repeated 25 and 10 measure 11 design 11 design 13 and 12 , 13 and 13 and 15 methods 13 and 16 , 13 and 17 we 13 and 19 found 13 and 25 and 14 advanced 15 methods 17 we 18 have 18 have 19 found 19 found 21 relationship 20 a 21 relationship 21 relationship 22 between 22 between 24 staffing 23 cna 24 staffing 25 and 28 quality 26 nursing 28 quality 27 home 28 quality background : suicide rates are [highest] among the elderly , yet research on suicide prevention in old age remains [a] much - neglected area . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 25 . 2 : 4 rates 2 : 5 are 2 : 10 , 2 : 22 - 3 suicide 4 rates 4 rates 5 are 5 are 7 among 7 among 9 elderly 8 the 9 elderly 10 , 11 yet 10 , 19 remains 11 yet 12 research 12 research 13 on 12 research 16 in 12 research 19 remains 13 on 15 prevention 14 suicide 15 prevention 16 in 18 age 17 old 18 age 19 remains 21 much 22 - 24 area 23 neglected 24 area aims : we carried out a systematic review to examine the results of interventions aimed at suicidal elderly persons and to identify successful strategies and areas needing further exploration . 0 ###LEFT-WALL### 1 aims 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 20 and 0 ###LEFT-WALL### 30 . 2 : 3 we 2 : 4 carried 3 we 4 carried 4 carried 5 out 4 carried 8 review 4 carried 9 to 6 a 8 review 7 systematic 8 review 9 to 20 and 10 examine 12 results 10 examine 15 aimed 10 examine 20 and 11 the 12 results 12 results 13 of 12 results 15 aimed 13 of 14 interventions 15 aimed 16 at 16 at 19 persons 17 suicidal 19 persons 18 elderly 19 persons 20 and 21 to 20 and 28 further 21 to 22 identify 22 identify 25 and 23 successful 24 strategies 24 strategies 25 and 25 and 26 areas 25 and 27 needing 28 further 29 exploration methods : searches through various electronic databases yielded 19 studies with an empirical evaluation of a suicide prevention or intervention program designed especially for adults aged 60 years and older . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 31 . 2 : 3 searches 3 searches 4 through 3 searches 8 yielded 4 through 7 databases 5 various 7 databases 6 electronic 7 databases 8 yielded 29 and 9 19 10 studies 10 studies 11 with 10 studies 15 of 10 studies 29 and 11 with 14 evaluation 12 an 13 empirical 12 an 14 evaluation 13 empirical 14 evaluation 15 of 28 years 16 a 17 suicide 16 a 28 years 17 suicide 18 prevention 18 prevention 19 or 19 or 21 program 19 or 22 designed 19 or 26 aged 20 intervention 21 program 22 designed 23 especially 23 especially 24 for 24 for 25 adults 26 aged 28 years 27 60 28 years 29 and 30 older results : most studies were centered on the reduction of risk factors ( depression screening and treatment , and decreasing isolation ) , but when gender was considered , programs were mostly efficient for women . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 36 . 2 : 4 studies 2 : 6 centered 2 : 24 but 3 most 4 studies 4 studies 5 were 5 were 6 centered 6 centered 7 on 7 on 9 reduction 8 the 9 reduction 9 reduction 10 of 10 of 12 factors 11 risk 12 factors 12 factors 19 and 13 ( 19 and 14 depression 15 screening 15 screening 16 and 16 and 17 treatment 16 and 19 and 18 , 19 and 19 and 21 isolation 19 and 22 ) 20 decreasing 21 isolation 23 , 24 but 24 but 30 programs 24 but 31 were 25 when 26 gender 25 when 28 considered 25 when 29 , 25 when 30 programs 26 gender 27 was 27 was 28 considered 30 programs 31 were 31 were 33 efficient 32 mostly 33 efficient 33 efficient 34 for 34 for 35 women the empirical evaluations of programs attending to the needs of high - risk older adults seemed positive ; most studies showed a reduction in the level of suicidal ideation of patients or in the suicide rate of the participating communities . 0 ###LEFT-WALL### 3 evaluations 0 ###LEFT-WALL### 16 seemed 0 ###LEFT-WALL### 18 ; 0 ###LEFT-WALL### 41 . 1 the 3 evaluations 2 empirical 3 evaluations 3 evaluations 4 of 3 evaluations 16 seemed 4 of 5 programs 5 programs 6 attending 6 attending 7 to 6 attending 15 adults 7 to 9 needs 8 the 9 needs 9 needs 10 of 10 of 13 risk 11 high 12 - 11 high 13 risk 14 older 15 adults 16 seemed 17 positive 18 ; 20 studies 18 ; 21 showed 19 most 20 studies 20 studies 21 showed 21 showed 23 reduction 21 showed 32 or 22 a 23 reduction 24 in 26 level 24 in 32 or 25 the 26 level 26 level 27 of 27 of 29 ideation 28 suicidal 29 ideation 29 ideation 30 of 30 of 31 patients 32 or 33 in 33 in 36 rate 34 the 36 rate 35 suicide 36 rate 36 rate 37 of 37 of 40 communities 38 the 40 communities 39 participating 40 communities however , not all studies used measures of suicidality to evaluate the outcome of the intervention , and rarely did they aim at improving protective factors . 0 ###LEFT-WALL### 5 studies 0 ###LEFT-WALL### 6 used 0 ###LEFT-WALL### 18 and 0 ###LEFT-WALL### 27 . 1 however 2 , 1 however 5 studies 3 not 4 all 4 all 5 studies 5 studies 6 used 6 used 7 measures 6 used 10 to 6 used 11 evaluate 7 measures 8 of 8 of 9 suicidality 10 to 11 evaluate 11 evaluate 13 outcome 12 the 13 outcome 13 outcome 14 of 14 of 16 intervention 15 the 16 intervention 17 , 18 and 18 and 19 rarely 18 and 22 aim 19 rarely 20 did 20 did 21 they 20 did 22 aim 22 aim 23 at 23 at 26 factors 24 improving 26 factors 25 protective 26 factors [non] - melanoma skin cancers are a common reality worldwide . 0 ###LEFT-WALL### 2 - 0 ###LEFT-WALL### 6 are 0 ###LEFT-WALL### 11 . 2 - 5 cancers 3 melanoma 5 cancers 4 skin 5 cancers 5 cancers 6 are 6 are 9 reality 6 are 10 worldwide 7 a 8 common 7 a 9 reality 8 common 9 reality the principal cause that determines the occurrence of these diseases is the exposition of the sun , which principally causes an alteration in the immune system . 0 ###LEFT-WALL### 3 cause 0 ###LEFT-WALL### 11 is 0 ###LEFT-WALL### 17 , 0 ###LEFT-WALL### 27 . 1 the 3 cause 2 principal 3 cause 3 cause 4 that 3 cause 5 determines 3 cause 11 is 4 that 5 determines 5 determines 7 occurrence 6 the 7 occurrence 7 occurrence 8 of 8 of 10 diseases 9 these 10 diseases 11 is 13 exposition 12 the 13 exposition 13 exposition 14 of 14 of 16 sun 15 the 16 sun 17 , 18 which 17 , 20 causes 18 which 20 causes 19 principally 20 causes 20 causes 22 alteration 20 causes 23 in 21 an 22 alteration 23 in 26 system 24 the 26 system 25 immune 26 system therefore , it is possible that other forms of innate or acquired alterations of the immune system could favor the occurrence of [non] [-] melanoma skin cancers . 0 ###LEFT-WALL### 3 it 0 ###LEFT-WALL### 4 is 0 ###LEFT-WALL### 28 . 1 therefore 2 , 1 therefore 3 it 3 it 4 is 4 is 5 possible 5 possible 6 that 6 that 8 forms 6 that 19 favor 7 other 8 forms 8 forms 9 of 8 forms 18 could 9 of 11 or 10 innate 11 or 11 or 13 alterations 11 or 14 of 12 acquired 13 alterations 14 of 17 system 15 the 17 system 16 immune 17 system 18 could 19 favor 19 favor 21 occurrence 20 the 21 occurrence 21 occurrence 22 of 22 of 27 cancers 25 melanoma 27 cancers 26 skin 27 cancers for example , several studies have demonstrated that immunosenescence creates an immunosuppressive state that encourages the development of malignances , and new discoveries have noted the importance of t [cells] and [in] particular of t regulatory cells ( treg ) and t receptor cd28 in this mechanism . 0 ###LEFT-WALL### 5 studies 0 ###LEFT-WALL### 7 demonstrated 0 ###LEFT-WALL### 21 and 0 ###LEFT-WALL### 48 . 1 for 2 example 2 example 3 , 2 example 5 studies 4 several 5 studies 5 studies 6 have 6 have 7 demonstrated 7 demonstrated 8 that 8 that 9 immunosenescence 8 that 10 creates 9 immunosenescence 10 creates 10 creates 13 state 11 an 12 immunosuppressive 11 an 13 state 12 immunosuppressive 13 state 13 state 14 that 13 state 15 encourages 14 that 15 encourages 15 encourages 17 development 16 the 17 development 17 development 18 of 18 of 19 malignances 20 , 21 and 21 and 23 discoveries 21 and 25 noted 22 new 23 discoveries 23 discoveries 24 have 24 have 25 noted 25 noted 44 cd28 26 the 27 importance 27 importance 28 of 27 importance 41 and 28 of 37 cells 29 t 31 and 31 and 33 particular 31 and 34 of 31 and 37 cells 34 of 35 t 36 regulatory 37 cells 37 cells 39 treg 38 ( 39 treg 39 treg 40 ) 41 and 42 t 41 and 43 receptor 43 receptor 44 cd28 44 cd28 45 in 45 in 47 mechanism 46 this 47 mechanism similar results are [obtained] analyzing the effect of immunosuppressive drugs . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 are 0 ###LEFT-WALL### 11 . 1 similar 2 results 2 results 3 are 3 are 5 analyzing 5 analyzing 7 effect 6 the 7 effect 7 effect 8 of 8 of 10 drugs 9 immunosuppressive 10 drugs the importance of the immune system and its alteration in the genesis of [non] [-] melanoma skin cancers is fundamental for the creation of a new therapeutic and less invasive approach . 0 ###LEFT-WALL### 2 importance 0 ###LEFT-WALL### 19 is 0 ###LEFT-WALL### 32 . 1 the 2 importance 2 importance 3 of 2 importance 10 in 2 importance 19 is 3 of 7 and 4 the 6 system 5 immune 6 system 6 system 7 and 7 and 9 alteration 8 its 9 alteration 10 in 12 genesis 11 the 12 genesis 12 genesis 13 of 13 of 18 cancers 16 melanoma 18 cancers 17 skin 18 cancers 19 is 20 fundamental 20 fundamental 21 for 21 for 23 creation 22 the 23 creation 23 creation 24 of 24 of 31 approach 25 a 26 new 25 a 31 approach 26 new 31 approach 27 therapeutic 28 and 28 and 30 invasive 28 and 31 approach 29 less 30 invasive cerebrovascular disease constitutes one of the main causes of morbidity , disability and mortality worldwide . 0 ###LEFT-WALL### 2 disease 0 ###LEFT-WALL### 3 constitutes 0 ###LEFT-WALL### 16 . 1 cerebrovascular 2 disease 2 disease 3 constitutes 3 constitutes 4 one 3 constitutes 15 worldwide 4 one 5 of 5 of 8 causes 6 the 7 main 6 the 8 causes 8 causes 9 of 9 of 13 and 10 morbidity 11 , 11 , 12 disability 11 , 13 and 13 and 14 mortality obesity , a major health problem reaching global epidemic proportions , is also associated with morbidity and mortality . 0 ###LEFT-WALL### 1 obesity 0 ###LEFT-WALL### 14 associated 0 ###LEFT-WALL### 19 . 1 obesity 6 problem 1 obesity 12 is 2 , 6 problem 3 a 4 major 3 a 6 problem 4 major 5 health 5 health 6 problem 6 problem 7 reaching 6 problem 11 , 7 reaching 10 proportions 8 global 10 proportions 9 epidemic 10 proportions 12 is 14 associated 13 also 14 associated 14 associated 15 with 15 with 17 and 16 morbidity 17 and 17 and 18 mortality the present review provides an update on the current knowledge regarding the association of gender and obesity with stroke prevalence and outcome . 0 ###LEFT-WALL### 3 review 0 ###LEFT-WALL### 4 provides 0 ###LEFT-WALL### 23 . 1 the 3 review 2 present 3 review 3 review 4 provides 4 provides 6 update 4 provides 7 on 4 provides 18 with 5 an 6 update 7 on 10 knowledge 8 the 10 knowledge 9 current 10 knowledge 10 knowledge 11 regarding 10 knowledge 14 of 11 regarding 13 association 12 the 13 association 14 of 16 and 15 gender 16 and 16 and 17 obesity 18 with 21 and 19 stroke 20 prevalence 20 prevalence 21 and 21 and 22 outcome we also discuss the areas that future research needs to point towards . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 discuss 0 ###LEFT-WALL### 13 . 1 we 3 discuss 2 also 3 discuss 3 discuss 5 areas 4 the 5 areas 5 areas 6 that 5 areas 12 towards 6 that 8 research 6 that 9 needs 7 future 8 research 8 research 9 needs 9 needs 10 to 9 needs 11 point 10 to 11 point 11 point 12 towards in general , gender differences in relation to stroke are increasingly being recognized and evaluated . 0 ###LEFT-WALL### 5 differences 0 ###LEFT-WALL### 10 are 0 ###LEFT-WALL### 16 . 1 in 4 gender 1 in 5 differences 2 general 3 , 2 general 4 gender 5 differences 6 in 5 differences 10 are 6 in 7 relation 7 relation 8 to 7 relation 9 stroke 8 to 9 stroke 10 are 11 increasingly 10 are 12 being 12 being 14 and 13 recognized 14 and 14 and 15 evaluated age - specific stroke incidence [is] generally higher [in] men , except in the elderly . 0 ###LEFT-WALL### 1 age 0 ###LEFT-WALL### 2 - 2 - 10 men 3 specific 4 stroke 4 stroke 10 men 5 incidence 10 men 7 generally 8 higher 8 higher 10 men 10 men 12 except 11 , 12 except 12 except 13 in 12 except 16 . 13 in 15 elderly 14 the 15 elderly women are treated less frequently with intravenous thrombolysis compared with men stroke patients and the two genders seem to respond differently to aspirin and statins . 0 ###LEFT-WALL### 1 women 0 ###LEFT-WALL### 18 seem 0 ###LEFT-WALL### 20 respond 0 ###LEFT-WALL### 26 . 1 women 2 are 2 are 3 treated 3 treated 5 frequently 3 treated 6 with 3 treated 10 with 4 less 5 frequently 6 with 8 thrombolysis 7 intravenous 8 thrombolysis 8 thrombolysis 9 compared 10 with 11 men 12 stroke 13 patients 13 patients 14 and 14 and 17 genders 14 and 18 seem 15 the 16 two 16 two 17 genders 18 seem 19 to 18 seem 20 respond 19 to 20 respond 20 respond 21 differently 20 respond 22 to 22 to 24 and 23 aspirin 24 and 24 and 25 statins regarding obesity , [although] it is a well - known predictor of cardiovascular disease , there is a growing body of evidence revealing the presence of an inverse relationship between obesity and outcome in patients with stroke or established cardiovascular disease , [the] so [-] called obesity paradox . 0 ###LEFT-WALL### 5 it 0 ###LEFT-WALL### 6 is 0 ###LEFT-WALL### 9 - 1 regarding 2 obesity 1 regarding 3 , 1 regarding 5 it 5 it 6 is 6 is 8 well 7 a 8 well 9 - 11 predictor 9 - 15 , 10 known 11 predictor 11 predictor 12 of 12 of 14 disease 13 cardiovascular 14 disease 15 , 16 there 15 , 17 is 16 there 17 is 17 is 20 body 18 a 20 body 19 growing 20 body 20 body 21 of 21 of 32 and 22 evidence 23 revealing 22 evidence 26 of 22 evidence 30 between 22 evidence 32 and 23 revealing 25 presence 24 the 25 presence 26 of 29 relationship 27 an 28 inverse 27 an 29 relationship 28 inverse 29 relationship 30 between 31 obesity 32 and 33 outcome 32 and 34 in 34 in 38 or 35 patients 36 with 35 patients 38 or 36 with 37 stroke 38 or 41 disease 38 or 46 called 39 established 41 disease 40 cardiovascular 41 disease 42 , 46 called 44 so 46 called 46 called 48 paradox 46 called 49 . 47 obesity 48 paradox further research is warranted on these important topics , as human population is continuously aging and [becoming] more obese . 0 ###LEFT-WALL### 2 research 0 ###LEFT-WALL### 4 warranted 0 ###LEFT-WALL### 9 , 0 ###LEFT-WALL### 20 . 1 further 2 research 2 research 3 is 3 is 4 warranted 4 warranted 5 on 5 on 8 topics 6 these 8 topics 7 important 8 topics 9 , 12 population 9 , 13 is 10 as 11 human 11 human 12 population 12 population 13 is 13 is 14 continuously 13 is 16 and 15 aging 16 and 16 and 19 obese 18 more 19 obese in this context , the causes of gender differences in stroke prevalence and outcome and the obesity - stroke paradox should be further investigated in future studies . 0 ###LEFT-WALL### 20 paradox 0 ###LEFT-WALL### 24 investigated 0 ###LEFT-WALL### 28 . 1 in 3 context 1 in 4 , 1 in 20 paradox 2 this 3 context 5 the 20 paradox 6 causes 7 of 6 causes 13 and 7 of 9 differences 8 gender 9 differences 9 differences 10 in 10 in 12 prevalence 11 stroke 12 prevalence 13 and 14 outcome 13 and 15 and 15 and 17 obesity 15 and 18 - 15 and 20 paradox 16 the 17 obesity 19 stroke 20 paradox 20 paradox 21 should 21 should 22 be 22 be 24 investigated 23 further 24 investigated 24 investigated 25 in 25 in 27 studies 26 future 27 studies multiple system atrophy ( msa ) is a fatal oligodendrogliopathy characterized by prominent α - synuclein inclusions resulting in a neuronal multisystem [degeneration] . 0 ###LEFT-WALL### 3 atrophy 0 ###LEFT-WALL### 7 is 0 ###LEFT-WALL### 24 . 1 multiple 2 system 2 system 3 atrophy 3 atrophy 5 msa 3 atrophy 7 is 4 ( 5 msa 5 msa 6 ) 7 is 10 oligodendrogliopathy 8 a 9 fatal 8 a 10 oligodendrogliopathy 9 fatal 10 oligodendrogliopathy 10 oligodendrogliopathy 11 characterized 10 oligodendrogliopathy 18 resulting 11 characterized 12 by 12 by 17 inclusions 13 prominent 16 synuclein 14 α 15 - 14 α 16 synuclein 16 synuclein 17 inclusions 18 resulting 19 in 19 in 22 multisystem 20 a 22 multisystem 21 neuronal 22 multisystem until recently msa was widely conceived as a nongenetic disorder . 0 ###LEFT-WALL### 3 msa 0 ###LEFT-WALL### 6 conceived 0 ###LEFT-WALL### 11 . 1 until 2 recently 1 until 3 msa 3 msa 4 was 4 was 6 conceived 5 widely 6 conceived 6 conceived 7 as 7 as 10 disorder 8 a 9 nongenetic 8 a 10 disorder 9 nongenetic 10 disorder however , during the last years a few postmortem verified mendelian pedigrees have been reported consistent with monogenic disease in rare cases of msa . 0 ###LEFT-WALL### 6 years 0 ###LEFT-WALL### 10 verified 0 ###LEFT-WALL### 25 . 1 however 2 , 1 however 6 years 3 during 5 last 3 during 6 years 4 the 5 last 6 years 8 few 6 years 9 postmortem 6 years 10 verified 7 a 8 few 8 few 9 postmortem 10 verified 11 mendelian 10 verified 20 in 11 mendelian 12 pedigrees 11 mendelian 14 been 11 mendelian 15 reported 11 mendelian 16 consistent 12 pedigrees 13 have 13 have 14 been 16 consistent 17 with 17 with 19 disease 18 monogenic 19 disease 20 in 22 cases 21 rare 22 cases 22 cases 23 of 23 of 24 msa further , within the last 2 decades several genes have been associated with an increased risk of msa , [first] and foremost the snca gene coding for α - synuclein . 0 ###LEFT-WALL### 9 genes 0 ###LEFT-WALL### 12 associated 0 ###LEFT-WALL### 31 . 1 further 2 , 1 further 9 genes 3 within 7 decades 3 within 9 genes 4 the 5 last 4 the 6 2 6 2 7 decades 8 several 9 genes 9 genes 10 have 10 have 11 been 11 been 12 associated 12 associated 13 with 13 with 16 risk 13 with 25 gene 14 an 16 risk 15 increased 16 risk 16 risk 17 of 17 of 21 and 18 msa 21 and 19 , 21 and 21 and 22 foremost 23 the 25 gene 24 snca 25 gene 25 gene 26 coding 26 coding 27 for 27 for 30 synuclein 28 α 29 - 28 α 30 synuclein moreover , genes involved in oxidative stress , mitochondrial dysfunction , inflammatory processes , as well as parkinsonism - and ataxia - related genes have been implicated as susceptibility factors . 0 ###LEFT-WALL### 20 and 0 ###LEFT-WALL### 27 implicated 0 ###LEFT-WALL### 31 . 1 moreover 2 , 1 moreover 20 and 3 genes 4 involved 3 genes 5 in 3 genes 17 as 3 genes 20 and 5 in 7 stress 6 oxidative 7 stress 7 stress 10 dysfunction 8 , 10 dysfunction 9 mitochondrial 10 dysfunction 10 dysfunction 13 processes 10 dysfunction 14 , 11 , 13 processes 12 inflammatory 13 processes 13 processes 14 , 15 as 16 well 16 well 17 as 17 as 18 parkinsonism 19 - 20 and 20 and 21 ataxia 20 and 25 have 22 - 23 related 23 related 24 genes 23 related 25 have 25 have 26 been 26 been 27 implicated 27 implicated 28 as 28 as 30 factors 29 susceptibility 30 factors in this review , we discuss the emerging evidence in favor of genetic players in msa . 0 ###LEFT-WALL### 5 we 0 ###LEFT-WALL### 6 discuss 0 ###LEFT-WALL### 17 . 1 in 3 review 1 in 4 , 1 in 5 we 2 this 3 review 5 we 6 discuss 6 discuss 9 evidence 6 discuss 10 in 6 discuss 15 in 7 the 9 evidence 8 emerging 9 evidence 10 in 11 favor 11 favor 12 of 12 of 14 players 13 genetic 14 players 15 in 16 msa aging coincides with a decline in llms . 0 ###LEFT-WALL### 1 aging 0 ###LEFT-WALL### 2 coincides 0 ###LEFT-WALL### 8 . 1 aging 2 coincides 2 coincides 3 with 2 coincides 6 in 3 with 5 decline 4 a 5 decline 6 in 7 llms preserving llms may be considered a very important determinant of functional independence in the elderly . 0 ###LEFT-WALL### 1 preserving 0 ###LEFT-WALL### 5 considered 0 ###LEFT-WALL### 16 . 1 preserving 2 llms 1 preserving 3 may 3 may 4 be 4 be 5 considered 5 considered 9 determinant 5 considered 13 in 6 a 7 very 6 a 9 determinant 7 very 8 important 8 important 9 determinant 9 determinant 10 of 10 of 12 independence 11 functional 12 independence 13 in 15 elderly 14 the 15 elderly to maintain [llms] the question arises whether habitual physical activities ( hpa ) can prevent a decline in llms . 0 ###LEFT-WALL### 1 to 0 ###LEFT-WALL### 20 . 1 to 2 maintain 2 maintain 5 question 2 maintain 6 arises 4 the 5 question 5 question 6 arises 6 arises 7 whether 7 whether 10 activities 7 whether 15 prevent 8 habitual 10 activities 9 physical 10 activities 10 activities 12 hpa 10 activities 14 can 11 ( 12 hpa 12 hpa 13 ) 14 can 15 prevent 15 prevent 17 decline 15 prevent 18 in 16 a 17 decline 18 in 19 llms this review aims to determine the relationship between hpa throughout life and llms above age 50 . 0 ###LEFT-WALL### 2 review 0 ###LEFT-WALL### 3 aims 0 ###LEFT-WALL### 17 . 1 this 2 review 2 review 3 aims 3 aims 4 to 3 aims 5 determine 4 to 5 determine 5 determine 7 relationship 5 determine 10 throughout 5 determine 14 above 6 the 7 relationship 7 relationship 8 between 8 between 9 hpa 10 throughout 12 and 11 life 12 and 12 and 13 llms 14 above 15 age 15 age 16 50 using relevant databases and keywords , 70 studies that met the inclusion criteria were reviewed and [where] possible , a meta - analysis was performed . 0 ###LEFT-WALL### 8 studies 0 ###LEFT-WALL### 15 reviewed 0 ###LEFT-WALL### 16 and 0 ###LEFT-WALL### 26 . 1 using 4 and 1 using 6 , 1 using 8 studies 2 relevant 3 databases 3 databases 4 and 4 and 5 keywords 7 70 8 studies 8 studies 9 that 8 studies 10 met 8 studies 14 were 9 that 10 met 10 met 13 criteria 11 the 13 criteria 12 inclusion 13 criteria 14 were 15 reviewed 16 and 23 analysis 16 and 24 was 18 possible 19 , 18 possible 23 analysis 20 a 23 analysis 21 meta 22 - 21 meta 23 analysis 23 analysis 24 was 24 was 25 performed the main findings are : [(] 1 [ )(the present level of hpa is positively related to llms [;] ( 2 ) hpa in the past has little effect on present llms [;] ( 3 ) hpa involving endurance have less influence on llms compared to hpa involving strength [;] ( 4 ) [people] with a stable [habitually] physically active life [are] able to delay a decline in llms [.] 1 the 3 findings 2 main 3 findings 3 findings 4 are 4 are 5 : 5 : 7 1 5 : 16 related 7 1 11 level 7 1 14 is 7 1 16 related 9 )(the 11 level 10 present 11 level 11 level 12 of 11 level 14 is 12 of 13 hpa 15 positively 16 related 16 related 23 hpa 16 related 27 has 17 to 18 llms 17 to 23 hpa 18 llms 21 2 20 ( 21 2 21 2 22 ) 23 hpa 24 in 23 hpa 27 has 24 in 26 past 25 the 26 past 27 has 29 effect 27 has 30 on 28 little 29 effect 30 on 31 present 31 present 37 hpa 31 present 42 influence 32 llms 35 3 32 llms 37 hpa 34 ( 35 3 35 3 36 ) 37 hpa 38 involving 37 hpa 40 have 38 involving 39 endurance 40 have 41 less 40 have 42 influence 42 influence 43 on 43 on 44 llms 44 llms 45 compared 44 llms 46 to 44 llms 55 with 46 to 47 hpa 47 hpa 48 involving 47 hpa 52 4 48 involving 49 strength 51 ( 52 4 52 4 53 ) 55 with 61 life 56 a 61 life 57 stable 61 life 59 physically 60 active 60 active 61 life 61 life 63 able 63 able 64 to 63 able 65 delay 64 to 65 delay 65 delay 67 decline 65 delay 68 in 66 a 67 decline 68 in 69 llms in conclusion , to obtain a high amount of llms during aging [,] it is important to achieve and maintain a high level of hpa with [mainly] muscle - strengthening activities . 0 ###LEFT-WALL### 2 conclusion 0 ###LEFT-WALL### 3 , 0 ###LEFT-WALL### 32 . 1 in 2 conclusion 3 , 4 to 3 , 19 and 3 , 29 - 4 to 19 and 5 obtain 10 llms 5 obtain 19 and 6 a 8 amount 7 high 8 amount 8 amount 9 of 8 amount 10 llms 9 of 10 llms 10 llms 11 during 10 llms 14 it 10 llms 18 achieve 11 during 12 aging 14 it 15 is 15 is 16 important 16 important 17 to 16 important 18 achieve 17 to 18 achieve 19 and 20 maintain 19 and 26 with 20 maintain 23 level 21 a 22 high 21 a 23 level 22 high 23 level 23 level 24 of 24 of 25 hpa 26 with 28 muscle 29 - 31 activities 30 strengthening 31 activities the effects of normal aging and orthopedic conditions on gait patterns [during] [customary] walking have been extensively investigated . 0 ###LEFT-WALL### 2 effects 0 ###LEFT-WALL### 18 investigated 0 ###LEFT-WALL### 19 . 1 the 2 effects 2 effects 3 of 2 effects 9 on 2 effects 14 walking 2 effects 15 have 3 of 8 conditions 4 normal 8 conditions 5 aging 6 and 6 and 7 orthopedic 6 and 8 conditions 9 on 11 patterns 10 gait 11 patterns 15 have 16 been 16 been 18 investigated 17 extensively 18 investigated empirical evidence supports the notion that sex differences exist in the gait patterns of young adults but it is unclear as to whether sex differences exist in older adults . 0 ###LEFT-WALL### 2 evidence 0 ###LEFT-WALL### 3 supports 0 ###LEFT-WALL### 17 but 0 ###LEFT-WALL### 30 . 1 empirical 2 evidence 2 evidence 3 supports 3 supports 5 notion 4 the 5 notion 5 notion 6 that 6 that 8 differences 6 that 9 exist 7 sex 8 differences 8 differences 9 exist 9 exist 10 in 10 in 13 patterns 11 the 13 patterns 12 gait 13 patterns 13 patterns 14 of 14 of 16 adults 15 young 16 adults 17 but 18 it 17 but 19 is 18 it 19 is 19 is 20 unclear 20 unclear 22 to 21 as 22 to 22 to 23 whether 23 whether 25 differences 23 whether 26 exist 24 sex 25 differences 25 differences 26 exist 26 exist 27 in 27 in 29 adults 28 older 29 adults the aim of this study was to investigate sex - specific differences in gait [among] older adults . 0 ###LEFT-WALL### 2 aim 0 ###LEFT-WALL### 10 - 0 ###LEFT-WALL### 18 . 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 9 sex 10 - 12 differences 11 specific 12 differences 12 differences 13 in 13 in 17 adults 14 gait 17 adults 16 older 17 adults study participants were 336 adults ( 50 - 96 years ; 162 women [ )(enrolled in the baltimore longitudinal study of aging ( blsa ) [who] completed walking tasks at [self] - selected speed without assistance . 0 ###LEFT-WALL### 2 participants 0 ###LEFT-WALL### 3 were 0 ###LEFT-WALL### 8 - 0 ###LEFT-WALL### 15 )(enrolled 1 study 2 participants 2 participants 3 were 3 were 5 adults 4 336 5 adults 5 adults 7 50 6 ( 7 50 7 50 8 - 8 - 10 years 8 - 11 ; 9 96 10 years 11 ; 13 women 12 162 13 women 13 women 15 )(enrolled 15 )(enrolled 16 in 16 in 19 longitudinal 17 the 19 longitudinal 18 baltimore 19 longitudinal 19 longitudinal 20 study 19 longitudinal 30 at 19 longitudinal 34 speed 20 study 21 of 20 study 27 completed 20 study 28 walking 20 study 29 tasks 21 of 24 blsa 22 aging 24 blsa 23 ( 24 blsa 24 blsa 25 ) 29 tasks 30 at 32 - 34 speed 33 selected 34 speed 34 speed 35 without 34 speed 37 . 35 without 36 assistance after adjusting for significant covariates , women walked with higher cadence [(] p=0.01 ) and shorter stride length ( p=0.006 ) compared to men , while gait speed was not significantly related to sex . 0 ###LEFT-WALL### 18 length 0 ###LEFT-WALL### 22 compared 1 after 15 and 1 after 18 length 2 adjusting 3 for 2 adjusting 15 and 3 for 5 covariates 4 significant 5 covariates 5 covariates 7 women 6 , 7 women 7 women 8 walked 7 women 14 ) 8 walked 9 with 9 with 13 p=0.01 10 higher 11 cadence 11 cadence 13 p=0.01 15 and 17 stride 16 shorter 17 stride 18 length 20 p=0.006 18 length 22 compared 19 ( 20 p=0.006 20 p=0.006 21 ) 22 compared 23 to 22 compared 26 while 23 to 24 men 25 , 26 while 26 while 28 speed 26 while 32 related 26 while 35 . 27 gait 28 speed 28 speed 29 was 29 was 30 not 29 was 32 related 31 significantly 32 related 32 related 33 to 33 to 34 sex women also had less hip range of motion ( rom [;] p=0.004 ) and greater ankle rom ( p<0.001 ) in the sagittal - plane , and greater hip rom ( p=0.004 ) in the frontal - plane . 0 ###LEFT-WALL### 1 women 0 ###LEFT-WALL### 3 had 0 ###LEFT-WALL### 39 . 1 women 3 had 2 also 3 had 3 had 30 rom 3 had 34 in 4 less 5 hip 5 hip 16 ankle 6 range 7 of 6 range 14 and 7 of 8 motion 8 motion 12 p=0.004 9 ( 12 p=0.004 10 rom 12 p=0.004 12 p=0.004 13 ) 14 and 15 greater 14 and 16 ankle 16 ankle 30 rom 17 rom 19 p<0.001 17 rom 21 in 17 rom 27 and 18 ( 19 p<0.001 19 p<0.001 20 ) 21 in 25 plane 22 the 25 plane 23 sagittal 24 - 23 sagittal 25 plane 26 , 27 and 27 and 28 greater 27 and 30 rom 29 hip 30 rom 30 rom 32 p=0.004 31 ( 32 p=0.004 32 p=0.004 33 ) 34 in 38 plane 35 the 38 plane 36 frontal 37 - 36 frontal 38 plane hip absorptive mechanical work expenditure ( mwe [ )(of the women [was] greater in the sagittal - plane ( p<0.001 ) and [lower] in the frontal - plane ( p<0.001 ) , compared to men . 0 ###LEFT-WALL### 5 expenditure 0 ###LEFT-WALL### 33 compared 0 ###LEFT-WALL### 36 . 1 hip 5 expenditure 2 absorptive 4 work 3 mechanical 4 work 4 work 5 expenditure 5 expenditure 7 mwe 5 expenditure 33 compared 6 ( 7 mwe 7 mwe 9 )(of 7 mwe 32 , 9 )(of 11 women 10 the 11 women 11 women 13 greater 13 greater 22 and 14 in 18 plane 14 in 22 and 15 the 18 plane 16 sagittal 17 - 16 sagittal 18 plane 18 plane 20 p<0.001 19 ( 20 p<0.001 20 p<0.001 21 ) 22 and 24 in 24 in 28 plane 25 the 28 plane 26 frontal 27 - 26 frontal 28 plane 28 plane 30 p<0.001 29 ( 30 p<0.001 30 p<0.001 31 ) 33 compared 34 to 34 to 35 men in summary , women 's gait is characterized by greater ankle rom than men while men tend to have greater hip rom than women . 0 ###LEFT-WALL### 2 summary 0 ###LEFT-WALL### 3 , 0 ###LEFT-WALL### 25 . 1 in 2 summary 3 , 6 gait 3 , 8 characterized 4 women 5 's 5 's 6 gait 6 gait 7 is 7 is 8 characterized 8 characterized 9 by 8 characterized 13 than 8 characterized 15 while 9 by 12 rom 10 greater 11 ankle 11 ankle 12 rom 13 than 14 men 15 while 16 men 15 while 17 tend 16 men 17 tend 17 tend 18 to 17 tend 19 have 18 to 19 have 19 have 22 rom 19 have 23 than 20 greater 21 hip 21 hip 22 rom 23 than 24 women characterizing unique gait patterns of women and men with aging may be beneficial for detecting the early stages of gait abnormalities that may lead to pathology . 0 ###LEFT-WALL### 1 characterizing 0 ###LEFT-WALL### 12 be 0 ###LEFT-WALL### 27 . 1 characterizing 4 patterns 1 characterizing 9 with 1 characterizing 11 may 2 unique 3 gait 3 gait 4 patterns 4 patterns 5 of 5 of 7 and 6 women 7 and 7 and 8 men 9 with 10 aging 11 may 12 be 12 be 13 beneficial 13 beneficial 14 for 14 for 15 detecting 15 detecting 18 stages 16 the 18 stages 17 early 18 stages 18 stages 19 of 18 stages 22 that 18 stages 23 may 19 of 21 abnormalities 20 gait 21 abnormalities 22 that 23 may 23 may 24 lead 24 lead 25 to 25 to 26 pathology as the body ages , it undergoes a multitude of changes . 0 ###LEFT-WALL### 6 it 0 ###LEFT-WALL### 7 undergoes 0 ###LEFT-WALL### 12 . 1 as 3 body 1 as 4 ages 1 as 5 , 1 as 6 it 2 the 3 body 3 body 4 ages 6 it 7 undergoes 7 undergoes 11 changes 8 a 9 multitude 9 multitude 10 of 9 multitude 11 changes 10 of 11 changes some of these changes are visible , whereas others are not [and] [may] be elicited during the patient encounter . 0 ###LEFT-WALL### 4 changes 0 ###LEFT-WALL### 5 are 1 some 2 of 1 some 4 changes 2 of 4 changes 3 these 4 changes 4 changes 5 are 5 are 6 visible 6 visible 8 whereas 7 , 8 whereas 8 whereas 9 others 8 whereas 15 elicited 8 whereas 20 . 9 others 10 are 10 are 11 not 10 are 14 be 14 be 15 elicited 15 elicited 16 during 16 during 19 encounter 17 the 19 encounter 18 patient 19 encounter some gastrointestinal issues may be more common in the elderly population and possibly in older women . 0 ###LEFT-WALL### 3 issues 0 ###LEFT-WALL### 5 be 0 ###LEFT-WALL### 17 . 1 some 3 issues 2 gastrointestinal 3 issues 3 issues 4 may 4 may 5 be 5 be 7 common 6 more 7 common 7 common 12 and 8 in 11 population 8 in 12 and 9 the 11 population 10 elderly 11 population 12 and 13 possibly 12 and 14 in 14 in 16 women 15 older 16 women these issues range from motility disorders , such as fecal incontinence and constipation , to changes in neuropeptide function and its effect on the anorexia of aging . 0 ###LEFT-WALL### 2 issues 0 ###LEFT-WALL### 3 range 0 ###LEFT-WALL### 28 . 1 these 2 issues 2 issues 3 range 3 range 4 from 3 range 23 on 4 from 20 and 5 motility 6 disorders 6 disorders 7 , 7 , 19 function 7 , 20 and 8 such 11 incontinence 9 as 10 fecal 10 fecal 11 incontinence 11 incontinence 12 and 12 and 13 constipation 12 and 14 , 12 and 15 to 12 and 19 function 15 to 16 changes 16 changes 17 in 17 in 18 neuropeptide 20 and 22 effect 21 its 22 effect 23 on 25 anorexia 24 the 25 anorexia 25 anorexia 26 of 26 of 27 aging this article comprehensively reviews gastrointestinal issues that commonly afflict the elderly female population . 0 ###LEFT-WALL### 2 article 0 ###LEFT-WALL### 4 reviews 0 ###LEFT-WALL### 14 . 1 this 2 article 2 article 4 reviews 3 comprehensively 4 reviews 4 reviews 6 issues 5 gastrointestinal 6 issues 6 issues 7 that 6 issues 9 afflict 7 that 9 afflict 8 commonly 9 afflict 9 afflict 13 population 10 the 13 population 11 elderly 13 population 12 female 13 population diastolic heart failure ( dhf ) is an important entity , the significance of which is increasingly recognized . 0 ###LEFT-WALL### 3 failure 0 ###LEFT-WALL### 7 is 0 ###LEFT-WALL### 11 , 0 ###LEFT-WALL### 19 . 1 diastolic 2 heart 2 heart 3 failure 3 failure 5 dhf 3 failure 7 is 4 ( 5 dhf 5 dhf 6 ) 7 is 10 entity 8 an 9 important 8 an 10 entity 9 important 10 entity 11 , 13 significance 11 , 18 recognized 12 the 13 significance 13 significance 14 of 13 significance 16 is 14 of 15 which 16 is 18 recognized 17 increasingly 18 recognized this report examines the available evidence regarding the role , significance , and mechanisms of dhf . 0 ###LEFT-WALL### 2 report 0 ###LEFT-WALL### 3 examines 0 ###LEFT-WALL### 10 , 0 ###LEFT-WALL### 17 . 1 this 2 report 2 report 3 examines 3 examines 6 evidence 4 the 6 evidence 5 available 6 evidence 6 evidence 7 regarding 7 regarding 9 role 8 the 9 role 10 , 13 and 11 significance 13 and 12 , 13 and 13 and 14 mechanisms 13 and 15 of 15 of 16 dhf epidemiologic studies have documented the rising burden of dhf , and experimental data are revealing the unique mechanisms distinguishing it from systolic heart failure . 0 ###LEFT-WALL### 1 epidemiologic 0 ###LEFT-WALL### 4 documented 0 ###LEFT-WALL### 25 . 1 epidemiologic 2 studies 1 epidemiologic 3 have 1 epidemiologic 4 documented 2 studies 3 have 4 documented 11 and 4 documented 14 are 5 the 7 burden 6 rising 7 burden 7 burden 8 of 7 burden 11 and 8 of 9 dhf 10 , 11 and 11 and 13 data 11 and 14 are 12 experimental 13 data 14 are 15 revealing 15 revealing 18 mechanisms 15 revealing 21 from 16 the 18 mechanisms 17 unique 18 mechanisms 18 mechanisms 19 distinguishing 19 distinguishing 20 it 21 from 24 failure 22 systolic 23 heart 23 heart 24 failure despite controversies on the definition of dhf , or heart failure with preserved ejection fraction , standardized clinical criteria with supplementary imaging and structural data have identified dhf as a distinct pathophysiological entity . 0 ###LEFT-WALL### 23 and 0 ###LEFT-WALL### 27 identified 0 ###LEFT-WALL### 34 . 1 despite 2 controversies 1 despite 16 , 1 despite 23 and 2 controversies 3 on 3 on 15 fraction 4 the 15 fraction 5 definition 6 of 5 definition 9 or 6 of 7 dhf 8 , 9 or 9 or 11 failure 9 or 12 with 9 or 15 fraction 10 heart 11 failure 12 with 14 ejection 13 preserved 14 ejection 17 standardized 19 criteria 18 clinical 19 criteria 19 criteria 20 with 19 criteria 23 and 20 with 22 imaging 21 supplementary 22 imaging 23 and 25 data 23 and 26 have 24 structural 25 data 26 have 27 identified 27 identified 28 dhf 27 identified 29 as 29 as 33 entity 30 a 31 distinct 30 a 33 entity 31 distinct 33 entity 32 pathophysiological 33 entity the mechanisms underlying dhf include abnormal matrix dynamics , altered myocyte cytoskeleton , and impaired active relaxation . 0 ###LEFT-WALL### 2 mechanisms 0 ###LEFT-WALL### 5 include 0 ###LEFT-WALL### 18 . 1 the 2 mechanisms 2 mechanisms 3 underlying 2 mechanisms 5 include 3 underlying 4 dhf 5 include 14 and 6 abnormal 7 matrix 7 matrix 8 dynamics 8 dynamics 9 , 9 , 12 cytoskeleton 9 , 14 and 10 altered 12 cytoskeleton 11 myocyte 12 cytoskeleton 13 , 14 and 14 and 17 relaxation 15 impaired 17 relaxation 16 active 17 relaxation the commonly held belief that survival of patients with dhf is better than that of patients with systolic heart failure has been challenged by updated data . 0 ###LEFT-WALL### 4 belief 0 ###LEFT-WALL### 23 challenged 0 ###LEFT-WALL### 27 . 1 the 4 belief 2 commonly 3 held 3 held 4 belief 4 belief 5 that 4 belief 21 has 5 that 6 survival 5 that 11 is 6 survival 7 of 6 survival 11 is 7 of 8 patients 8 patients 9 with 9 with 10 dhf 11 is 12 better 12 better 13 than 13 than 14 that 13 than 15 of 15 of 16 patients 16 patients 17 with 17 with 20 failure 18 systolic 19 heart 19 heart 20 failure 21 has 22 been 22 been 23 challenged 23 challenged 24 by 24 by 26 data 25 updated 26 data the heterogeneous etiologies or risk factors for the condition include aging , diabetes , hypertension , and ischemia , making a common diagnostic or treatment pathway [difficult] . 0 ###LEFT-WALL### 2 heterogeneous 0 ###LEFT-WALL### 4 or 0 ###LEFT-WALL### 28 . 1 the 2 heterogeneous 2 heterogeneous 4 or 3 etiologies 4 or 4 or 5 risk 4 or 7 for 5 risk 6 factors 7 for 17 and 8 the 10 include 9 condition 10 include 10 include 11 aging 10 include 12 , 12 , 13 diabetes 12 , 14 , 14 , 15 hypertension 14 , 17 and 16 , 17 and 17 and 18 ischemia 17 and 19 , 17 and 20 making 20 making 24 or 21 a 23 diagnostic 22 common 23 diagnostic 23 diagnostic 24 or 24 or 26 pathway 25 treatment 26 pathway novel therapeutic targets that address the pathophysiology of this disease are under consideration , although there are no proven therapies for dhf to date . 0 ###LEFT-WALL### 3 targets 0 ###LEFT-WALL### 11 are 1 novel 3 targets 2 therapeutic 3 targets 3 targets 4 that 3 targets 5 address 3 targets 11 are 4 that 5 address 5 address 7 pathophysiology 6 the 7 pathophysiology 7 pathophysiology 8 of 8 of 10 disease 9 this 10 disease 11 are 12 under 11 are 15 although 12 under 13 consideration 14 , 15 although 15 although 16 there 15 although 17 are 15 although 25 . 16 there 17 are 17 are 20 therapies 18 no 20 therapies 19 proven 20 therapies 20 therapies 21 for 21 for 22 dhf 22 dhf 24 date 23 to 24 date exacerbating factors include volume and sodium indiscretion , arrhythmias , ischemia , and comorbidities . 0 ###LEFT-WALL### 2 factors 0 ###LEFT-WALL### 3 include 0 ###LEFT-WALL### 15 . 1 exacerbating 2 factors 2 factors 3 include 3 include 13 and 4 volume 5 and 5 and 7 indiscretion 5 and 8 , 6 sodium 7 indiscretion 8 , 9 arrhythmias 8 , 10 , 10 , 11 ischemia 10 , 13 and 12 , 13 and 13 and 14 comorbidities strategies to ameliorate [or] to obviate these precipitating factors are most effective in preventing dhf and its exacerbations . 0 ###LEFT-WALL### 1 strategies 0 ###LEFT-WALL### 10 are 0 ###LEFT-WALL### 19 . 1 strategies 2 to 1 strategies 3 ameliorate 1 strategies 10 are 2 to 3 ameliorate 3 ameliorate 5 to 5 to 6 obviate 6 obviate 9 factors 7 these 9 factors 8 precipitating 9 factors 10 are 12 effective 11 most 12 effective 12 effective 13 in 13 in 14 preventing 14 preventing 16 and 15 dhf 16 and 16 and 18 exacerbations 17 its 18 exacerbations meanwhile , prevention of dhf through appropriate and aggressive risk factor identification and management must remain the cornerstone of clinical intervention . 0 ###LEFT-WALL### 3 prevention 0 ###LEFT-WALL### 22 . 1 meanwhile 2 , 1 meanwhile 3 prevention 3 prevention 4 of 3 prevention 15 must 4 of 5 dhf 5 dhf 6 through 6 through 13 and 7 appropriate 8 and 8 and 9 aggressive 8 and 12 identification 10 risk 11 factor 11 factor 12 identification 12 identification 13 and 13 and 14 management 15 must 16 remain 16 remain 18 cornerstone 17 the 18 cornerstone 18 cornerstone 19 of 19 of 21 intervention 20 clinical 21 intervention physical signs of old age may be obvious , but mental and cognitive changes require more careful observation . 0 ###LEFT-WALL### 2 signs 0 ###LEFT-WALL### 7 be 0 ###LEFT-WALL### 10 but 0 ###LEFT-WALL### 19 . 1 physical 2 signs 2 signs 3 of 2 signs 6 may 3 of 5 age 4 old 5 age 6 may 7 be 7 be 8 obvious 9 , 10 but 10 but 14 changes 10 but 15 require 11 mental 12 and 12 and 13 cognitive 12 and 14 changes 14 changes 15 require 15 require 18 observation 16 more 18 observation 17 careful 18 observation changes in behavior may represent the earliest indications of medical problems , or disorders of the central nervous system , and these may be bidirectional . 0 ###LEFT-WALL### 1 changes 0 ###LEFT-WALL### 5 represent 0 ###LEFT-WALL### 13 or 0 ###LEFT-WALL### 26 . 1 changes 2 in 1 changes 4 may 2 in 3 behavior 4 may 5 represent 5 represent 8 indications 6 the 7 earliest 6 the 8 indications 8 indications 9 of 9 of 11 problems 10 medical 11 problems 12 , 13 or 13 or 14 disorders 13 or 24 be 14 disorders 15 of 14 disorders 23 may 15 of 21 and 16 the 19 system 17 central 19 system 18 nervous 19 system 19 system 21 and 20 , 21 and 21 and 22 these 23 may 24 be 24 be 25 bidirectional cognitive dysfunction [syndrome] is underdiagnosed and affects a substantial portion of aged companion animals . 0 ###LEFT-WALL### 2 dysfunction 0 ###LEFT-WALL### 6 and 0 ###LEFT-WALL### 15 . 1 cognitive 2 dysfunction 2 dysfunction 6 and 4 is 5 underdiagnosed 4 is 6 and 6 and 7 affects 6 and 10 portion 8 a 9 substantial 8 a 10 portion 9 substantial 10 portion 10 portion 11 of 11 of 14 animals 12 aged 13 companion 13 companion 14 animals this article describes potential treatment regimens to address age - related behavioral problems , as well as a framework for investigating differential diagnoses . 0 ###LEFT-WALL### 2 article 0 ###LEFT-WALL### 3 describes 0 ###LEFT-WALL### 24 . 1 this 2 article 2 article 3 describes 3 describes 6 regimens 3 describes 7 to 3 describes 17 as 4 potential 5 treatment 5 treatment 6 regimens 7 to 8 address 8 address 9 age 9 age 13 problems 10 - 13 problems 11 related 13 problems 12 behavioral 13 problems 13 problems 14 , 15 as 16 well 16 well 17 as 17 as 19 framework 18 a 19 framework 19 framework 20 for 20 for 21 investigating 21 investigating 23 diagnoses 22 differential 23 diagnoses early identification of changes in behavior is essential for the adequate treatment and management of medical and behavioral problems , and for monitoring outcomes . 0 ###LEFT-WALL### 2 identification 0 ###LEFT-WALL### 7 is 0 ###LEFT-WALL### 25 . 1 early 2 identification 2 identification 3 of 2 identification 7 is 3 of 4 changes 4 changes 5 in 5 in 6 behavior 7 is 8 essential 8 essential 21 and 9 for 13 and 9 for 21 and 10 the 12 treatment 11 adequate 12 treatment 12 treatment 13 and 13 and 14 management 13 and 15 of 15 of 19 problems 16 medical 17 and 17 and 18 behavioral 17 and 19 problems 20 , 21 and 21 and 22 for 22 for 23 monitoring 23 monitoring 24 outcomes the " pawspice " philosophy , which the author introduced at the 2000 american veterinary medical association meeting , focuses on symptom management along with a kinder , gentler , [or] modified approach to standard therapy . 0 ###LEFT-WALL### 5 philosophy 0 ###LEFT-WALL### 20 focuses 0 ###LEFT-WALL### 37 . 1 the 2 " 1 the 5 philosophy 3 pawspice 4 " 3 pawspice 5 philosophy 5 philosophy 7 which 5 philosophy 20 focuses 6 , 7 which 7 which 10 introduced 7 which 19 , 8 the 9 author 9 author 10 introduced 10 introduced 11 at 11 at 17 association 12 the 13 2000 13 2000 17 association 14 american 17 association 15 veterinary 16 medical 16 medical 17 association 17 association 18 meeting 20 focuses 21 on 20 focuses 25 with 20 focuses 34 to 21 on 23 management 22 symptom 23 management 24 along 25 with 25 with 33 approach 26 a 33 approach 27 kinder 28 , 27 kinder 33 approach 29 gentler 30 , 29 gentler 33 approach 32 modified 33 approach 34 to 36 therapy 35 standard 36 therapy many veterinarians have preconceived bias or ingrained beliefs about aging , serious illness , multiple comorbidities , and cancer , which may cause a negative or dismissive approach toward palliative treatment , especially in geriatric pets . 0 ###LEFT-WALL### 2 veterinarians 0 ###LEFT-WALL### 6 or 0 ###LEFT-WALL### 37 . 1 many 2 veterinarians 2 veterinarians 6 or 3 have 5 bias 3 have 6 or 4 preconceived 5 bias 6 or 7 ingrained 6 or 33 especially 7 ingrained 18 and 8 beliefs 9 about 8 beliefs 11 , 9 about 10 aging 11 , 13 illness 11 , 14 , 12 serious 13 illness 14 , 16 comorbidities 14 , 18 and 15 multiple 16 comorbidities 17 , 18 and 18 and 19 cancer 18 and 21 which 20 , 21 which 21 which 22 may 21 which 32 , 22 may 23 cause 23 cause 28 approach 23 cause 29 toward 24 a 28 approach 25 negative 26 or 26 or 27 dismissive 26 or 28 approach 29 toward 31 treatment 30 palliative 31 treatment 33 especially 34 in 34 in 36 pets 35 geriatric 36 pets veterinarians and their [v] [-] teams must overcome this insensitive attitude about life - limiting disease . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 8 overcome 1 veterinarians 2 and 2 and 6 teams 2 and 7 must 3 their 6 teams 7 must 8 overcome 8 overcome 11 attitude 8 overcome 12 about 9 this 10 insensitive 10 insensitive 11 attitude 12 about 13 life 13 life 15 limiting 14 - 15 limiting 15 limiting 16 disease 15 limiting 17 . this article describes assessment , treatment , and home management of some nonpainful life - limiting diseases , including cancer and age - related decline of vital functions in the pawspice setting . 0 ###LEFT-WALL### 2 article 0 ###LEFT-WALL### 3 describes 0 ###LEFT-WALL### 33 . 1 this 2 article 2 article 3 describes 3 describes 10 management 3 describes 29 in 4 assessment 5 , 5 , 6 treatment 5 , 8 and 7 , 8 and 8 and 9 home 8 and 10 management 10 management 11 of 10 management 21 and 10 management 25 decline 10 management 26 of 11 of 14 life 12 some 14 life 13 nonpainful 14 life 14 life 16 limiting 15 - 16 limiting 16 limiting 17 diseases 16 limiting 18 , 19 including 20 cancer 20 cancer 21 and 21 and 22 age 21 and 23 - 21 and 24 related 21 and 25 decline 26 of 28 functions 27 vital 28 functions 29 in 31 pawspice 30 the 31 pawspice 31 pawspice 32 setting in many cases bilateral cortical activation in older adults has been associated with better task performance , suggesting that a greater reliance on interhemispheric interactions aids performance . 0 ###LEFT-WALL### 6 activation 0 ###LEFT-WALL### 12 associated 1 in 3 cases 1 in 6 activation 2 many 3 cases 4 bilateral 6 activation 5 cortical 6 activation 6 activation 7 in 6 activation 10 has 7 in 9 adults 8 older 9 adults 10 has 11 been 11 been 12 associated 12 associated 13 with 13 with 16 performance 14 better 15 task 15 task 16 performance 16 performance 18 suggesting 17 , 18 suggesting 18 suggesting 19 that 18 suggesting 28 . 19 that 22 reliance 19 that 26 aids 20 a 22 reliance 21 greater 22 reliance 22 reliance 23 on 22 reliance 26 aids 23 on 25 interactions 24 interhemispheric 25 interactions 26 aids 27 performance interhemispheric communication is primarily mediated via the corpus callosum ( cc ) , however with advancing age the anterior half of [the] cc undergoes significant atrophy . 0 ###LEFT-WALL### 2 communication 0 ###LEFT-WALL### 5 mediated 0 ###LEFT-WALL### 13 , 0 ###LEFT-WALL### 27 . 1 interhemispheric 2 communication 2 communication 3 is 3 is 5 mediated 4 primarily 5 mediated 5 mediated 6 via 6 via 9 callosum 7 the 9 callosum 8 corpus 9 callosum 9 callosum 11 cc 10 ( 11 cc 11 cc 12 ) 13 , 20 half 13 , 24 undergoes 14 however 20 half 15 with 17 age 15 with 19 anterior 15 with 20 half 16 advancing 17 age 18 the 19 anterior 20 half 21 of 20 half 24 undergoes 21 of 23 cc 24 undergoes 26 atrophy 25 significant 26 atrophy here we determine whether there are age differences in the relationship between cross [-] sectional area of [the] cc and performance on cognitive tests of psychomotor processing speed and working memory . 0 ###LEFT-WALL### 2 we 0 ###LEFT-WALL### 3 determine 0 ###LEFT-WALL### 32 . 1 here 2 we 2 we 3 determine 3 determine 4 whether 3 determine 22 on 4 whether 5 there 4 whether 6 are 5 there 6 are 6 are 8 differences 7 age 8 differences 8 differences 9 in 8 differences 12 between 9 in 11 relationship 10 the 11 relationship 12 between 20 and 13 cross 16 area 15 sectional 16 area 16 area 17 of 16 area 20 and 17 of 19 cc 20 and 21 performance 22 on 24 tests 23 cognitive 24 tests 24 tests 25 of 25 of 29 and 26 psychomotor 28 speed 27 processing 28 speed 28 speed 29 and 29 and 31 memory 30 working 31 memory we found that older adults had significantly smaller callosal area in the anterior and mid - body of [the] cc than young adults . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 found 0 ###LEFT-WALL### 24 . 1 we 2 found 2 found 3 that 3 that 5 adults 3 that 6 had 4 older 5 adults 5 adults 6 had 6 had 10 area 6 had 11 in 6 had 21 than 7 significantly 8 smaller 8 smaller 10 area 9 callosal 10 area 11 in 14 and 12 the 13 anterior 13 anterior 14 and 14 and 17 body 14 and 18 of 15 mid 16 - 15 mid 17 body 18 of 20 cc 21 than 23 adults 22 young 23 adults furthermore , older adults with larger size in these callosal areas performed better on assessments of working memory and processing speed . 0 ###LEFT-WALL### 4 adults 0 ###LEFT-WALL### 12 performed 0 ###LEFT-WALL### 22 . 1 furthermore 2 , 1 furthermore 4 adults 3 older 4 adults 4 adults 5 with 4 adults 12 performed 5 with 7 size 6 larger 7 size 7 size 8 in 8 in 11 areas 9 these 11 areas 10 callosal 11 areas 12 performed 13 better 13 better 14 on 14 on 19 and 15 assessments 16 of 15 assessments 19 and 16 of 17 working 17 working 18 memory 19 and 21 speed 20 processing 21 speed our results indicate that older adults with larger size of the anterior half of [the] cc exhibit better [cognitive] function , although their performance was still poorer than young adults with similar [cc] size . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 26 still 0 ###LEFT-WALL### 35 . 1 our 2 results 2 results 3 indicate 3 indicate 4 that 4 that 6 adults 4 that 20 function 5 older 6 adults 6 adults 7 with 6 adults 20 function 7 with 9 size 8 larger 9 size 9 size 10 of 9 size 13 half 9 size 17 exhibit 10 of 12 anterior 11 the 12 anterior 13 half 14 of 13 half 17 exhibit 14 of 16 cc 18 better 20 function 20 function 22 although 21 , 22 although 22 although 24 performance 23 their 24 performance 24 performance 25 was 25 was 26 still 26 still 30 adults 26 still 31 with 27 poorer 30 adults 28 than 29 young 29 young 30 adults 31 with 34 size 32 similar 34 size thus , while the capability for interhemispheric interactions , [as] inferred from callosal size , may provide performance benefits for older adults , this capacity alone does not assure protection from general performance [decline] . 0 ###LEFT-WALL### 25 capacity 0 ###LEFT-WALL### 29 assure 0 ###LEFT-WALL### 35 . 1 thus 2 , 1 thus 25 capacity 3 while 5 capability 3 while 17 provide 3 while 23 , 3 while 25 capacity 4 the 5 capability 5 capability 6 for 5 capability 11 inferred 5 capability 16 may 6 for 8 interactions 7 interhemispheric 8 interactions 9 , 11 inferred 11 inferred 12 from 11 inferred 15 , 12 from 14 size 13 callosal 14 size 16 may 17 provide 17 provide 19 benefits 18 performance 19 benefits 19 benefits 20 for 20 for 22 adults 21 older 22 adults 24 this 25 capacity 25 capacity 27 does 26 alone 27 does 27 does 28 not 27 does 29 assure 29 assure 30 protection 29 assure 31 from 31 from 33 performance 32 general 33 performance the ageing population is currently one of the main issues facing uk healthcare systems . 0 ###LEFT-WALL### 3 population 0 ###LEFT-WALL### 4 is 0 ###LEFT-WALL### 15 . 1 the 3 population 2 ageing 3 population 3 population 4 is 4 is 5 currently 4 is 6 one 6 one 7 of 7 of 10 issues 8 the 9 main 8 the 10 issues 10 issues 11 facing 11 facing 14 systems 12 uk 14 systems 13 healthcare 14 systems nurses of the future will be faced with the task of caring for this elderly population . 0 ###LEFT-WALL### 1 nurses 0 ###LEFT-WALL### 7 faced 0 ###LEFT-WALL### 17 . 1 nurses 2 of 1 nurses 5 will 2 of 4 future 3 the 4 future 5 will 6 be 6 be 7 faced 7 faced 8 with 8 with 10 task 9 the 10 task 10 task 11 of 11 of 12 caring 12 caring 13 for 13 for 16 population 14 this 15 elderly 15 elderly 16 population meanwhile , care standards and government policies have emphasized the need for preparing students to care for the older people . 0 ###LEFT-WALL### 5 and 0 ###LEFT-WALL### 9 emphasized 0 ###LEFT-WALL### 21 . 1 meanwhile 2 , 1 meanwhile 5 and 3 care 4 standards 4 standards 5 and 5 and 7 policies 5 and 8 have 6 government 7 policies 8 have 9 emphasized 9 emphasized 11 need 9 emphasized 12 for 10 the 11 need 12 for 13 preparing 13 preparing 14 students 13 preparing 15 to 13 preparing 16 care 15 to 16 care 16 care 17 for 17 for 20 people 18 the 20 people 19 older 20 people preparing nursing students to meet the care needs of an expanding ageing population is a challenge for nursing education . 0 ###LEFT-WALL### 1 preparing 0 ###LEFT-WALL### 14 is 0 ###LEFT-WALL### 20 . 1 preparing 3 students 1 preparing 4 to 1 preparing 5 meet 1 preparing 14 is 2 nursing 3 students 4 to 5 meet 5 meet 8 needs 6 the 8 needs 7 care 8 needs 8 needs 9 of 9 of 13 population 10 an 13 population 11 expanding 12 ageing 12 ageing 13 population 14 is 16 challenge 15 a 16 challenge 16 challenge 17 for 17 for 18 nursing 18 nursing 19 education moreover , caring [for] older people are often not seen by students as an attractive option , a perception that exerts a considerable influence on the values that inform their future professional practice . 0 ###LEFT-WALL### 6 people 0 ###LEFT-WALL### 10 seen 1 moreover 2 , 1 moreover 6 people 3 caring 6 people 5 older 6 people 6 people 7 are 7 are 9 not 7 are 10 seen 8 often 9 not 10 seen 11 by 10 seen 13 as 11 by 12 students 13 as 16 option 14 an 15 attractive 14 an 16 option 15 attractive 16 option 16 option 19 perception 17 , 19 perception 18 a 19 perception 19 perception 20 that 19 perception 21 exerts 19 perception 34 . 20 that 21 exerts 21 exerts 24 influence 21 exerts 25 on 22 a 24 influence 23 considerable 24 influence 25 on 27 values 26 the 27 values 27 values 28 that 27 values 29 inform 28 that 29 inform 29 inform 33 practice 30 their 33 practice 31 future 33 practice 32 professional 33 practice this paper examines the literature related to the students ' perceptions of caring for older people and suggests the need for specific curricular content , teaching and a structured approach to the educational preparation and support of students for their practice experience . 0 ###LEFT-WALL### 27 and 0 ###LEFT-WALL### 43 . 1 this 2 paper 2 paper 17 and 2 paper 27 and 3 examines 5 literature 3 examines 7 to 3 examines 17 and 4 the 5 literature 5 literature 6 related 7 to 11 perceptions 8 the 9 students 9 students 10 ' 10 ' 11 perceptions 11 perceptions 12 of 12 of 13 caring 13 caring 14 for 14 for 16 people 15 older 16 people 17 and 18 suggests 17 and 20 need 17 and 21 for 19 the 20 need 21 for 26 teaching 22 specific 26 teaching 23 curricular 26 teaching 24 content 25 , 24 content 26 teaching 27 and 30 approach 27 and 31 to 27 and 37 of 28 a 30 approach 29 structured 30 approach 31 to 35 and 32 the 34 preparation 33 educational 34 preparation 34 preparation 35 and 35 and 36 support 37 of 38 students 38 students 39 for 39 for 42 experience 40 their 42 experience 41 practice 42 experience if students are provided with the relevant preparation and support , they can engage in enriched learning experiences , deliver quality care and develop positive attitudes in caring for older people in their professional practice . 0 ###LEFT-WALL### 12 they 0 ###LEFT-WALL### 14 engage 0 ###LEFT-WALL### 19 , 0 ###LEFT-WALL### 36 . 1 if 2 students 1 if 9 and 1 if 11 , 1 if 12 they 2 students 3 are 3 are 9 and 4 provided 5 with 4 provided 9 and 5 with 8 preparation 6 the 8 preparation 7 relevant 8 preparation 9 and 10 support 12 they 13 can 13 can 14 engage 14 engage 15 in 14 engage 18 experiences 15 in 17 learning 16 enriched 17 learning 19 , 23 and 20 deliver 22 care 20 deliver 23 and 21 quality 22 care 23 and 24 develop 24 develop 26 attitudes 25 positive 26 attitudes 26 attitudes 27 in 27 in 28 caring 28 caring 29 for 29 for 31 people 30 older 31 people 31 people 32 in 32 in 35 practice 33 their 35 practice 34 professional 35 practice oxidative stress is known to play a relevant role in down [syndrome] ( ds ) and its effects are documented from embryonic life . 0 ###LEFT-WALL### 2 stress 0 ###LEFT-WALL### 4 known 0 ###LEFT-WALL### 16 and 0 ###LEFT-WALL### 24 . 1 oxidative 2 stress 2 stress 3 is 3 is 4 known 4 known 5 to 4 known 6 play 5 to 6 play 6 play 9 role 6 play 10 in 7 a 9 role 8 relevant 9 role 10 in 14 ds 11 down 14 ds 13 ( 14 ds 14 ds 15 ) 16 and 18 effects 16 and 20 documented 17 its 18 effects 18 effects 19 are 19 are 20 documented 20 documented 21 from 21 from 23 life 22 embryonic 23 life oxidative dna damage has been shown to be significantly elevated in down syndrome patients , and this has been indicated as an early event promoting neurodegeneration and alzheimer type dementia . 0 ###LEFT-WALL### 3 damage 0 ###LEFT-WALL### 6 shown 0 ###LEFT-WALL### 31 . 1 oxidative 3 damage 2 dna 3 damage 3 damage 4 has 4 has 5 been 5 been 6 shown 6 shown 7 to 6 shown 20 indicated 7 to 8 be 7 to 18 has 8 be 9 significantly 8 be 10 elevated 10 elevated 11 in 11 in 16 and 12 down 14 patients 13 syndrome 14 patients 14 patients 16 and 15 , 16 and 16 and 17 this 18 has 19 been 19 been 20 indicated 20 indicated 21 as 21 as 27 and 22 an 23 early 22 an 24 event 23 early 24 event 24 event 25 promoting 24 event 27 and 25 promoting 26 neurodegeneration 27 and 30 dementia 28 alzheimer 29 type 29 type 30 dementia the aim of this study was to investigate the efficacy of coenzyme q ( 10 ) ( coq ( 10 ) ) in delaying the effect of oxidative damage in these patients . 0 ###LEFT-WALL### 2 aim 0 ###LEFT-WALL### 33 . 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 efficacy 8 investigate 23 in 9 the 10 efficacy 10 efficacy 11 of 11 of 12 coenzyme 12 coenzyme 13 q 12 coenzyme 15 10 12 coenzyme 18 coq 14 ( 15 10 15 10 16 ) 17 ( 18 coq 18 coq 20 10 18 coq 22 ) 19 ( 20 10 20 10 21 ) 23 in 24 delaying 24 delaying 26 effect 24 delaying 30 in 25 the 26 effect 26 effect 27 of 27 of 29 damage 28 oxidative 29 damage 30 in 32 patients 31 these 32 patients in our previous study we demonstrated a mild protective effect of coq ( 10 ) on dna , although the treatment was unable to modify the overall extent of oxidative damage at the patient level . 0 ###LEFT-WALL### 5 we 0 ###LEFT-WALL### 6 demonstrated 1 in 4 study 1 in 5 we 2 our 3 previous 2 our 4 study 5 we 6 demonstrated 6 demonstrated 10 effect 6 demonstrated 16 on 6 demonstrated 19 although 7 a 8 mild 7 a 10 effect 8 mild 10 effect 9 protective 10 effect 10 effect 11 of 10 effect 14 10 11 of 12 coq 13 ( 14 10 14 10 15 ) 16 on 17 dna 18 , 19 although 19 although 21 treatment 19 although 22 was 19 although 36 . 20 the 21 treatment 21 treatment 22 was 22 was 23 unable 23 unable 24 to 23 unable 25 modify 24 to 25 modify 25 modify 28 extent 25 modify 32 at 26 the 28 extent 27 overall 28 extent 28 extent 29 of 29 of 31 damage 30 oxidative 31 damage 32 at 35 level 33 the 35 level 34 patient 35 level possible limitations of the previous study were : time of treatment ( 6 months ) or spectrum of dna lesions detected . 0 ###LEFT-WALL### 1 possible 0 ###LEFT-WALL### 7 were 0 ###LEFT-WALL### 8 : 1 possible 7 were 2 limitations 3 of 2 limitations 7 were 3 of 6 study 4 the 5 previous 4 the 6 study 8 : 16 or 8 : 22 . 9 time 10 of 9 time 16 or 10 of 11 treatment 11 treatment 14 months 12 ( 14 months 13 6 14 months 14 months 15 ) 16 or 17 spectrum 16 or 18 of 16 or 21 detected 18 of 20 lesions 19 dna 20 lesions in order to overcome these limitations we planned a continuation of the trial aimed at evaluating the effects of coq ( 10 ) following a prolonged treatment . 0 ###LEFT-WALL### 7 we 0 ###LEFT-WALL### 8 planned 0 ###LEFT-WALL### 28 . 1 in 2 order 1 in 7 we 2 order 3 to 2 order 4 overcome 3 to 4 overcome 4 overcome 6 limitations 5 these 6 limitations 7 we 8 planned 8 planned 10 continuation 9 a 10 continuation 10 continuation 11 of 11 of 13 trial 12 the 13 trial 13 trial 14 aimed 14 aimed 15 at 15 at 16 evaluating 16 evaluating 18 effects 17 the 18 effects 18 effects 19 of 18 effects 24 following 19 of 20 coq 20 coq 22 10 21 ( 22 10 22 10 23 ) 24 following 27 treatment 25 a 27 treatment 26 prolonged 27 treatment our results highlight an age - specific reduction in the percentage of cells showing the highest amount of oxidized bases , indicating a potential role of coq ( 10 ) in modulating dna repair mechanisms . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 highlight 0 ###LEFT-WALL### 36 . 1 our 2 results 2 results 3 highlight 3 highlight 5 age 3 highlight 22 indicating 3 highlight 31 in 4 an 5 age 5 age 8 reduction 6 - 8 reduction 7 specific 8 reduction 8 reduction 9 in 8 reduction 12 of 8 reduction 21 , 9 in 11 percentage 10 the 11 percentage 12 of 13 cells 13 cells 14 showing 14 showing 17 amount 15 the 16 highest 15 the 17 amount 17 amount 18 of 18 of 20 bases 19 oxidized 20 bases 21 , 22 indicating 22 indicating 25 role 22 indicating 30 ) 23 a 24 potential 23 a 25 role 24 potential 25 role 25 role 26 of 26 of 27 coq 27 coq 29 10 28 ( 29 10 29 10 30 ) 31 in 35 mechanisms 32 modulating 35 mechanisms 33 dna 34 repair 34 repair 35 mechanisms cerebral small vessel disease ( csvd ) is considered to be caused by an increased permeability of the blood - brain barrier and results in enlargement of virchow robin spaces ( vrs ) , white matter lesions , brain microbleeds , and lacunar [infarcts] . 0 ###LEFT-WALL### 4 disease 0 ###LEFT-WALL### 9 considered 0 ###LEFT-WALL### 20 - 0 ###LEFT-WALL### 45 . 1 cerebral 4 disease 2 small 4 disease 3 vessel 4 disease 4 disease 6 csvd 4 disease 8 is 5 ( 6 csvd 6 csvd 7 ) 8 is 9 considered 9 considered 10 to 9 considered 12 caused 10 to 11 be 11 be 12 caused 12 caused 13 by 13 by 16 permeability 14 an 16 permeability 15 increased 16 permeability 16 permeability 17 of 17 of 19 blood 18 the 19 blood 20 - 22 barrier 20 - 23 and 21 brain 22 barrier 23 and 24 results 23 and 39 brain 24 results 25 in 24 results 27 of 24 results 37 lesions 24 results 39 brain 25 in 26 enlargement 27 of 30 spaces 28 virchow 30 spaces 29 robin 30 spaces 30 spaces 32 vrs 31 ( 32 vrs 32 vrs 33 ) 34 , 37 lesions 35 white 37 lesions 36 matter 37 lesions 37 lesions 38 , 39 brain 42 and 40 microbleeds 42 and 41 , 42 and 42 and 43 lacunar the increased permeability of the blood [-] brain barrier may relate to endothelial cell activation and activated monocytes/macrophages . 0 ###LEFT-WALL### 3 permeability 0 ###LEFT-WALL### 16 and 0 ###LEFT-WALL### 19 . 1 the 3 permeability 2 increased 3 permeability 3 permeability 4 of 3 permeability 16 and 4 of 9 barrier 5 the 9 barrier 6 blood 9 barrier 8 brain 9 barrier 10 may 11 relate 10 may 16 and 11 relate 12 to 12 to 15 activation 13 endothelial 14 cell 14 cell 15 activation 16 and 17 activated 16 and 18 monocytes/macrophages therefore , we hypothesized that plasma markers of endothelial activation ( adhesion molecules ) and monocyte/macrophage activation ( neopterin ) relate to csvd manifestations . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 hypothesized 0 ###LEFT-WALL### 25 . 1 therefore 2 , 1 therefore 3 we 3 we 4 hypothesized 4 hypothesized 5 that 5 that 15 and 5 that 21 relate 6 plasma 7 markers 7 markers 8 of 7 markers 15 and 8 of 10 activation 9 endothelial 10 activation 10 activation 13 molecules 11 ( 13 molecules 12 adhesion 13 molecules 13 molecules 14 ) 15 and 17 activation 15 and 19 neopterin 15 and 21 relate 16 monocyte/macrophage 17 activation 18 ( 19 neopterin 19 neopterin 20 ) 21 relate 22 to 22 to 24 manifestations 23 csvd 24 manifestations in 163 first - ever lacunar stroke patients and 183 essential hypertensive patients , we assessed csvd manifestations on brain magnetic resonance imaging ( mri ) and levels of c - reactive protein ( crp ) , neopterin , as well as circulating soluble adhesion molecules ( sicam - 1 , svcam - 1 , se - selectin , sp - selectin ) . 0 ###LEFT-WALL### 15 we 0 ###LEFT-WALL### 16 assessed 0 ###LEFT-WALL### 27 and 0 ###LEFT-WALL### 64 . 1 in 2 163 1 in 15 we 3 first 4 - 3 first 15 we 4 - 5 ever 5 ever 9 and 5 ever 14 , 5 ever 15 we 6 lacunar 8 patients 7 stroke 8 patients 8 patients 9 and 9 and 13 patients 10 183 13 patients 11 essential 13 patients 12 hypertensive 13 patients 15 we 16 assessed 16 assessed 18 manifestations 16 assessed 19 on 17 csvd 18 manifestations 19 on 23 imaging 20 brain 23 imaging 21 magnetic 22 resonance 22 resonance 23 imaging 23 imaging 25 mri 24 ( 25 mri 25 mri 26 ) 27 and 28 levels 27 and 52 svcam 28 levels 29 of 28 levels 33 protein 28 levels 52 svcam 29 of 30 c 31 - 33 protein 32 reactive 33 protein 33 protein 35 crp 33 protein 38 neopterin 33 protein 42 as 33 protein 51 , 34 ( 35 crp 35 crp 36 ) 37 , 38 neopterin 38 neopterin 39 , 39 , 42 as 40 as 41 well 41 well 42 as 42 as 46 molecules 42 as 51 , 43 circulating 45 adhesion 44 soluble 45 adhesion 45 adhesion 46 molecules 46 molecules 49 - 47 ( 49 - 48 sicam 49 - 49 - 50 1 49 - 51 , 52 svcam 54 1 52 svcam 61 - 53 - 54 1 55 , 61 - 56 se 58 selectin 56 se 59 , 56 se 60 sp 57 - 58 selectin 58 selectin 59 , 60 sp 61 - 61 - 62 selectin 61 - 63 ) neopterin , sicam - 1 [and] svcam - 1 levels were higher in patients with extensive csvd manifestations than in those without ( p < 0.01 ) . 0 ###LEFT-WALL### 1 neopterin 0 ###LEFT-WALL### 2 , 0 ###LEFT-WALL### 3 sicam 0 ###LEFT-WALL### 28 . 2 , 3 sicam 3 sicam 7 svcam 3 sicam 25 < 4 - 5 1 5 1 7 svcam 7 svcam 10 levels 7 svcam 22 without 8 - 9 1 9 1 10 levels 10 levels 11 were 11 were 12 higher 12 higher 13 in 12 higher 15 with 12 higher 19 than 12 higher 22 without 13 in 14 patients 15 with 18 manifestations 16 extensive 18 manifestations 17 csvd 18 manifestations 19 than 20 in 20 in 21 those 23 ( 25 < 24 p 25 < 25 < 26 0.01 25 < 27 ) neopterin levels independently related to higher numbers of enlarged virchow robin spaces ( p < 0.001 ) . 0 ###LEFT-WALL### 1 neopterin 0 ###LEFT-WALL### 4 related 2 levels 4 related 3 independently 4 related 4 related 5 to 4 related 18 . 5 to 12 spaces 6 higher 7 numbers 7 numbers 8 of 7 numbers 12 spaces 8 of 12 spaces 9 enlarged 12 spaces 10 virchow 11 robin 11 robin 12 spaces 12 spaces 15 < 13 ( 15 < 14 p 15 < 15 < 16 0.001 15 < 17 ) an inflammatory process with activated monocytes/macrophages may play a role in the increased permeability of the blood brain barrier in patients with csvd . 0 ###LEFT-WALL### 3 process 0 ###LEFT-WALL### 8 play 0 ###LEFT-WALL### 24 . 1 an 2 inflammatory 1 an 3 process 2 inflammatory 3 process 3 process 4 with 3 process 7 may 4 with 6 monocytes/macrophages 5 activated 6 monocytes/macrophages 7 may 8 play 8 play 10 role 8 play 11 in 8 play 20 in 8 play 22 with 9 a 10 role 11 in 14 permeability 12 the 14 permeability 13 increased 14 permeability 14 permeability 15 of 15 of 19 barrier 16 the 19 barrier 17 blood 18 brain 18 brain 19 barrier 20 in 21 patients 22 with 23 csvd dry skin is a common problem in the older individual due to physiological changes of the aging process as well as chronic health conditions . 0 ###LEFT-WALL### 2 skin 0 ###LEFT-WALL### 3 is 0 ###LEFT-WALL### 25 . 1 dry 2 skin 2 skin 3 is 3 is 6 problem 3 is 7 in 4 a 6 problem 5 common 6 problem 7 in 10 individual 8 the 10 individual 9 older 10 individual 10 individual 12 to 11 due 12 to 12 to 14 changes 13 physiological 14 changes 14 changes 15 of 15 of 18 process 16 the 18 process 17 aging 18 process 18 process 21 as 19 as 20 well 20 well 21 as 21 as 24 conditions 22 chronic 23 health 23 health 24 conditions dry skin can worsen if management is inappropriate or lacking . 0 ###LEFT-WALL### 2 skin 0 ###LEFT-WALL### 4 worsen 0 ###LEFT-WALL### 11 . 1 dry 2 skin 2 skin 3 can 3 can 4 worsen 4 worsen 5 if 5 if 6 management 5 if 7 is 6 management 7 is 7 is 9 or 8 inappropriate 9 or 9 or 10 lacking nursing management of dry skin in the elderly is comprehensive including applying topical products to replenish lipids and reduce water loss , maintaining or increasing fluid intake , limiting sun exposure , and reducing symptoms of chronic illnesses . 0 ###LEFT-WALL### 1 nursing 0 ###LEFT-WALL### 9 is 0 ###LEFT-WALL### 39 . 1 nursing 2 management 1 nursing 9 is 2 management 3 of 2 management 6 in 3 of 5 skin 4 dry 5 skin 6 in 8 elderly 7 the 8 elderly 9 is 33 and 10 comprehensive 11 including 10 comprehensive 22 , 11 including 14 products 12 applying 14 products 13 topical 14 products 14 products 15 to 14 products 18 and 15 to 18 and 16 replenish 17 lipids 16 replenish 18 and 18 and 19 reduce 19 reduce 21 loss 20 water 21 loss 22 , 23 maintaining 22 , 24 or 24 or 27 intake 24 or 29 limiting 24 or 33 and 25 increasing 27 intake 26 fluid 27 intake 28 , 29 limiting 29 limiting 31 exposure 29 limiting 32 , 30 sun 31 exposure 32 , 33 and 33 and 35 symptoms 33 and 36 of 34 reducing 35 symptoms 36 of 38 illnesses 37 chronic 38 illnesses the representation of social interaction in episodic memory is a critical factor for the successful navigation of social relationships . 0 ###LEFT-WALL### 2 representation 0 ###LEFT-WALL### 9 is 0 ###LEFT-WALL### 20 . 1 the 2 representation 2 representation 3 of 2 representation 9 is 3 of 5 interaction 4 social 5 interaction 5 interaction 6 in 6 in 8 memory 7 episodic 8 memory 9 is 12 factor 10 a 11 critical 10 a 12 factor 11 critical 12 factor 12 factor 13 for 13 for 16 navigation 14 the 16 navigation 15 successful 16 navigation 16 navigation 17 of 17 of 19 relationships 18 social 19 relationships in general , it is important to separate episodic memory during social interaction from episodic memory during the self - generation of action events . 0 ###LEFT-WALL### 4 it 0 ###LEFT-WALL### 5 is 0 ###LEFT-WALL### 20 - 0 ###LEFT-WALL### 25 . 1 in 2 general 2 general 3 , 2 general 4 it 4 it 5 is 5 is 6 important 6 important 7 to 6 important 8 separate 7 to 8 separate 8 separate 10 memory 8 separate 11 during 8 separate 17 during 9 episodic 10 memory 11 during 13 interaction 12 social 13 interaction 13 interaction 14 from 14 from 16 memory 15 episodic 16 memory 17 during 19 self 18 the 19 self 20 - 21 generation 21 generation 22 of 22 of 24 events 23 action 24 events different cortical representations have been associated with social interaction [vs] . self - generated episodic memory . 0 ###LEFT-WALL### 3 representations 0 ###LEFT-WALL### 6 associated 0 ###LEFT-WALL### 11 . 1 different 3 representations 2 cortical 3 representations 3 representations 4 have 4 have 5 been 5 been 6 associated 6 associated 7 with 7 with 9 interaction 8 social 9 interaction 11 . 12 self 11 . 13 - 11 . 17 . 13 - 16 memory 14 generated 16 memory 15 episodic 16 memory here we clarified the cortical representation of the effect of context ( social [vs] [.] solitary ) [on] episodic memory by comparing it with the generation effect [(] self [vs] [.] [other] ) on episodic memory . 0 ###LEFT-WALL### 2 we 0 ###LEFT-WALL### 3 clarified 0 ###LEFT-WALL### 37 . 1 here 2 we 2 we 3 clarified 3 clarified 6 representation 3 clarified 34 on 4 the 6 representation 5 cortical 6 representation 6 representation 7 of 6 representation 10 of 7 of 9 effect 8 the 9 effect 10 of 11 context 11 context 20 memory 12 ( 20 memory 13 social 20 memory 16 solitary 17 ) 16 solitary 20 memory 19 episodic 20 memory 20 memory 21 by 20 memory 33 ) 21 by 22 comparing 22 comparing 23 it 22 comparing 24 with 24 with 29 self 25 the 29 self 26 generation 29 self 27 effect 29 self 34 on 36 memory 35 episodic 36 memory each participant learned words while engaged in a sentence generation and a reading task , and subsequently each participant was scanned with functional magnetic resonance imaging ( fmri ) while they performed a recognition task using the words that had been learned . 0 ###LEFT-WALL### 2 participant 0 ###LEFT-WALL### 3 learned 0 ###LEFT-WALL### 16 and 0 ###LEFT-WALL### 43 . 1 each 2 participant 2 participant 3 learned 3 learned 4 words 3 learned 5 while 5 while 6 engaged 6 engaged 7 in 7 in 11 and 8 a 10 generation 9 sentence 10 generation 10 generation 11 and 11 and 14 task 11 and 15 , 12 a 14 task 13 reading 14 task 16 and 19 participant 16 and 21 scanned 17 subsequently 19 participant 18 each 19 participant 19 participant 20 was 20 was 21 scanned 21 scanned 22 with 21 scanned 30 while 22 with 25 resonance 22 with 26 imaging 23 functional 25 resonance 24 magnetic 25 resonance 26 imaging 28 fmri 27 ( 28 fmri 28 fmri 29 ) 30 while 31 they 30 while 42 learned 31 they 32 performed 32 performed 35 task 33 a 35 task 34 recognition 35 task 35 task 36 using 35 task 42 learned 36 using 38 words 36 using 42 learned 37 the 38 words 38 words 39 that 38 words 40 had 39 that 40 had 40 had 41 been the experiment was comprised of four conditions and we looked at two situations that involved a social context and [non] [-] social ( solitary ) context [task] . 0 ###LEFT-WALL### 2 experiment 0 ###LEFT-WALL### 4 comprised 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 15 involved 1 the 2 experiment 2 experiment 3 was 3 was 4 comprised 4 comprised 5 of 5 of 7 conditions 6 four 7 conditions 8 and 9 we 8 and 10 looked 9 we 10 looked 10 looked 11 at 11 at 13 situations 12 two 13 situations 13 situations 14 that 13 situations 15 involved 14 that 15 involved 15 involved 19 and 16 a 17 social 16 a 18 context 17 social 18 context 18 context 19 and 19 and 22 social 19 and 26 context 23 ( 26 context 24 solitary 25 ) 24 solitary 26 context 26 context 28 . in the learning session before entering the mri , two participants collaborated in a social context either generating ( social - contextual self - generation condition : ss [ )( reading [(] social - contextual [other] - generation condition : [so] ) [a] sequence of sentences alternately to construct a meaningful story narrative . 0 ###LEFT-WALL### 11 participants 0 ###LEFT-WALL### 12 collaborated 1 in 4 session 1 in 11 participants 2 the 4 session 3 learning 4 session 4 session 5 before 6 entering 8 mri 6 entering 9 , 6 entering 11 participants 7 the 8 mri 10 two 11 participants 11 participants 12 collaborated 12 collaborated 13 in 13 in 16 context 14 a 16 context 15 social 16 context 16 context 18 generating 17 either 18 generating 18 generating 24 - 18 generating 28 ss 19 ( 24 - 20 social 21 - 20 social 23 self 22 contextual 23 self 23 self 24 - 24 - 25 generation 25 generation 26 condition 25 generation 27 : 26 condition 27 : 28 ss 31 reading 31 reading 33 social 33 social 44 sequence 34 - 44 sequence 35 contextual 38 generation 35 contextual 42 ) 35 contextual 44 sequence 37 - 38 generation 38 generation 39 condition 38 generation 40 : 38 generation 42 ) 39 condition 40 : 44 sequence 45 of 44 sequence 48 to 44 sequence 49 construct 44 sequence 54 . 45 of 46 sentences 47 alternately 48 to 48 to 49 construct 49 construct 53 narrative 50 a 51 meaningful 50 a 53 narrative 51 meaningful 52 story 52 story 53 narrative in [the] [non] - social context , the participants generated [(] [non] - social - contextual self - generation condition : ns ) [or] read [(] [non] - social - contextual [other] - generation condition : no ) [a] sequence [of] sentences individually . 0 ###LEFT-WALL### 1 in 0 ###LEFT-WALL### 4 - 4 - 6 context 4 - 13 - 5 social 6 context 6 context 9 participants 7 , 9 participants 8 the 9 participants 9 participants 10 generated 9 participants 13 - 13 - 17 self 13 - 21 : 14 social 15 - 14 social 17 self 16 contextual 17 self 17 self 20 condition 18 - 20 condition 19 generation 20 condition 20 condition 21 : 21 : 22 ns 21 : 25 read 21 : 28 - 21 : 30 - 22 ns 23 ) 22 ns 25 read 25 read 28 - 28 - 29 social 30 - 35 condition 30 - 36 : 31 contextual 33 - 31 contextual 34 generation 34 generation 35 condition 36 : 40 sequence 36 : 44 . 37 no 38 ) 37 no 40 sequence 40 sequence 42 sentences 40 sequence 43 individually the stimuli for the recognition session consisted of learned words and novel words . 0 ###LEFT-WALL### 2 stimuli 0 ###LEFT-WALL### 7 consisted 0 ###LEFT-WALL### 14 . 1 the 2 stimuli 2 stimuli 3 for 2 stimuli 7 consisted 3 for 6 session 4 the 6 session 5 recognition 6 session 7 consisted 8 of 8 of 11 and 9 learned 10 words 10 words 11 and 11 and 13 words 12 novel 13 words activation for social context retrieval was identified in the right medial prefrontal cortex ( mpfc ) , and activation for self [-] generated retrieval was identified in the left mpfc and the left middle cingulate cortex . 0 ###LEFT-WALL### 1 activation 0 ###LEFT-WALL### 7 identified 0 ###LEFT-WALL### 18 and 0 ###LEFT-WALL### 37 . 1 activation 2 for 1 activation 6 was 2 for 5 retrieval 3 social 5 retrieval 4 context 5 retrieval 6 was 7 identified 7 identified 8 in 8 in 13 cortex 9 the 13 cortex 10 right 13 cortex 11 medial 13 cortex 12 prefrontal 13 cortex 13 cortex 15 mpfc 14 ( 15 mpfc 15 mpfc 16 ) 17 , 18 and 18 and 19 activation 18 and 26 identified 19 activation 20 for 19 activation 25 was 20 for 24 retrieval 21 self 23 generated 23 generated 24 retrieval 25 was 26 identified 26 identified 27 in 27 in 31 and 28 the 30 mpfc 29 left 30 mpfc 30 mpfc 31 and 31 and 36 cortex 32 the 36 cortex 33 left 36 cortex 34 middle 36 cortex 35 cingulate 36 cortex these results indicate that dissociable regions within the medial prefrontal cortices contribute to the processes involved in the representation of social interaction , including social context and self - generation in the retrieval of episodic memory . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 indicate 0 ###LEFT-WALL### 37 . 1 these 2 results 2 results 3 indicate 3 indicate 6 regions 3 indicate 12 contribute 4 that 5 dissociable 5 dissociable 6 regions 6 regions 7 within 6 regions 12 contribute 7 within 11 cortices 8 the 11 cortices 9 medial 11 cortices 10 prefrontal 11 cortices 12 contribute 13 to 12 contribute 17 in 12 contribute 24 including 12 contribute 30 generation 12 contribute 31 in 13 to 15 processes 14 the 15 processes 15 processes 16 involved 17 in 19 representation 18 the 19 representation 19 representation 20 of 20 of 22 interaction 21 social 22 interaction 23 , 24 including 24 including 27 and 24 including 29 - 25 social 26 context 26 context 27 and 27 and 28 self 31 in 33 retrieval 32 the 33 retrieval 33 retrieval 34 of 34 of 36 memory 35 episodic 36 memory sensorimotor performance declines with normal aging . 0 ###LEFT-WALL### 2 performance 0 ###LEFT-WALL### 3 declines 0 ###LEFT-WALL### 7 . 1 sensorimotor 2 performance 2 performance 3 declines 3 declines 4 with 4 with 6 aging 5 normal 6 aging the present study explored age - related changes in sensorimotor integration by conditioning a supra - threshold transcranial magnetic stimulation pulse with a peripheral nerve shock at different interstimulus intervals . 0 ###LEFT-WALL### 5 age 0 ###LEFT-WALL### 7 related 0 ###LEFT-WALL### 31 . 1 the 5 age 2 present 3 study 3 study 4 explored 4 explored 5 age 6 - 7 related 7 related 8 changes 7 related 9 in 7 related 12 by 9 in 11 integration 10 sensorimotor 11 integration 12 by 13 conditioning 13 conditioning 21 pulse 13 conditioning 27 at 14 a 15 supra 14 a 21 pulse 15 supra 16 - 15 supra 21 pulse 17 threshold 21 pulse 18 transcranial 20 stimulation 19 magnetic 20 stimulation 20 stimulation 21 pulse 21 pulse 22 with 22 with 26 shock 23 a 24 peripheral 23 a 26 shock 24 peripheral 25 nerve 25 nerve 26 shock 27 at 30 intervals 28 different 29 interstimulus 29 interstimulus 30 intervals cortical [motor] [threshold] of the abductor pollicis brevis muscle , intracortical inhibition and facilitation were measured . 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 15 were 0 ###LEFT-WALL### 17 . 1 cortical 4 of 1 cortical 10 , 4 of 7 pollicis 5 the 7 pollicis 6 abductor 7 pollicis 7 pollicis 8 brevis 7 pollicis 9 muscle 8 brevis 9 muscle 10 , 12 inhibition 10 , 13 and 11 intracortical 12 inhibition 13 and 14 facilitation 13 and 15 were 15 were 16 measured we also assessed the influence of median nerve stimulation on motor cortex excitability at intervals which evoked short - and long - latency afferent inhibition ( sai and lai , respectively ) and afferent - induced facilitation ( aif ) . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 assessed 0 ###LEFT-WALL### 41 . 1 we 3 assessed 2 also 3 assessed 3 assessed 33 and 3 assessed 36 induced 4 the 5 influence 5 influence 6 of 5 influence 33 and 6 of 9 stimulation 7 median 8 nerve 8 nerve 9 stimulation 9 stimulation 10 on 9 stimulation 16 which 9 stimulation 17 evoked 10 on 13 excitability 11 motor 12 cortex 12 cortex 13 excitability 13 excitability 14 at 14 at 15 intervals 16 which 17 evoked 17 evoked 20 and 17 evoked 31 respectively 18 short 20 and 19 - 20 and 20 and 25 inhibition 20 and 29 lai 21 long 22 - 21 long 23 latency 23 latency 25 inhibition 24 afferent 25 inhibition 26 ( 29 lai 27 sai 28 and 28 and 29 lai 29 lai 30 , 30 , 31 respectively 31 respectively 32 ) 33 and 34 afferent 33 and 35 - 33 and 36 induced 36 induced 37 facilitation 37 facilitation 39 aif 38 ( 39 aif 39 aif 40 ) we observed a marked decrease of the long latency influence of proprioceptive inputs on m1 excitability in the elderly , with the loss of aif and lai . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 observed 1 we 2 observed 2 observed 5 decrease 2 observed 14 on 2 observed 17 in 2 observed 21 with 3 a 5 decrease 4 marked 5 decrease 5 decrease 6 of 6 of 10 influence 7 the 10 influence 8 long 9 latency 9 latency 10 influence 10 influence 11 of 11 of 13 inputs 12 proprioceptive 13 inputs 14 on 16 excitability 15 m1 16 excitability 17 in 19 elderly 18 the 19 elderly 20 , 21 with 21 with 23 loss 21 with 28 . 22 the 23 loss 23 loss 24 of 24 of 27 lai 25 aif 26 and 26 and 27 lai the sai , motor thresholds and intracortical inhibition and facilitation were not age - related . 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 11 were 1 the 2 sai 2 sai 3 , 3 , 5 thresholds 3 , 6 and 4 motor 5 thresholds 6 and 8 inhibition 6 and 9 and 7 intracortical 8 inhibition 9 and 10 facilitation 9 and 11 were 11 were 12 not 11 were 13 age 13 age 15 related 14 - 15 related 15 related 16 . decreased sensorimotor performance with aging appears to be associated with a decrease in the influence of proprioceptive inputs on motor cortex excitability at longer intervals ( probably via higher order cortical areas ) . 0 ###LEFT-WALL### 3 performance 0 ###LEFT-WALL### 6 appears 0 ###LEFT-WALL### 34 . 1 decreased 2 sensorimotor 2 sensorimotor 3 performance 3 performance 4 with 3 performance 6 appears 4 with 5 aging 6 appears 7 to 6 appears 9 associated 7 to 8 be 8 be 9 associated 9 associated 10 with 9 associated 13 in 9 associated 19 on 9 associated 23 at 10 with 12 decrease 11 a 12 decrease 13 in 15 influence 14 the 15 influence 15 influence 16 of 16 of 18 inputs 17 proprioceptive 18 inputs 19 on 22 excitability 20 motor 21 cortex 21 cortex 22 excitability 23 at 25 intervals 24 longer 25 intervals 25 intervals 28 via 26 ( 27 probably 26 ( 28 via 28 via 32 areas 28 via 33 ) 29 higher 30 order 30 order 32 areas 31 cortical 32 areas depression commonly occurs in conjunction with a variety of medical conditions . 0 ###LEFT-WALL### 1 depression 0 ###LEFT-WALL### 3 occurs 0 ###LEFT-WALL### 12 . 1 depression 3 occurs 2 commonly 3 occurs 3 occurs 6 with 4 in 5 conjunction 5 conjunction 6 with 6 with 8 variety 7 a 8 variety 8 variety 9 of 9 of 11 conditions 10 medical 11 conditions in addition , family members who care for patients with medical diagnoses often suffer from depression . 0 ###LEFT-WALL### 5 members 0 ###LEFT-WALL### 14 suffer 0 ###LEFT-WALL### 17 . 1 in 2 addition 1 in 3 , 1 in 5 members 4 family 5 members 5 members 6 who 5 members 7 care 5 members 14 suffer 6 who 7 care 7 care 8 for 7 care 10 with 8 for 9 patients 10 with 12 diagnoses 11 medical 12 diagnoses 13 often 14 suffer 14 suffer 15 from 15 from 16 depression therefore , in addition to treating illnesses , physicians and other healthcare professionals are often faced with managing secondary mental health consequences . 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 16 faced 0 ###LEFT-WALL### 23 . 1 therefore 2 , 1 therefore 10 and 3 in 4 addition 3 in 10 and 4 addition 5 to 5 to 6 treating 7 illnesses 8 , 8 , 9 physicians 8 , 10 and 10 and 13 professionals 10 and 14 are 11 other 13 professionals 12 healthcare 13 professionals 14 are 15 often 14 are 16 faced 16 faced 17 with 17 with 18 managing 18 managing 22 consequences 19 secondary 21 health 20 mental 21 health 21 health 22 consequences we conducted a systematic review and meta - analysis of the association between activity restriction and depression in medical patients and their caregivers . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 conducted 0 ###LEFT-WALL### 24 . 1 we 2 conducted 2 conducted 6 and 2 conducted 13 between 2 conducted 18 in 3 a 4 systematic 3 a 5 review 4 systematic 5 review 5 review 6 and 6 and 9 analysis 6 and 10 of 7 meta 8 - 7 meta 9 analysis 10 of 12 association 11 the 12 association 13 between 16 and 14 activity 15 restriction 15 restriction 16 and 16 and 17 depression 18 in 21 and 19 medical 20 patients 20 patients 21 and 21 and 23 caregivers 22 their 23 caregivers a total of 34 studies ( n = 8053 ) documenting the relationship between activity restriction and depression were identified for the period between january 1980 and june 2010 . 0 ###LEFT-WALL### 27 and 0 ###LEFT-WALL### 30 . 1 a 2 total 2 total 3 of 2 total 11 documenting 2 total 27 and 3 of 5 studies 4 34 5 studies 5 studies 8 = 6 ( 8 = 7 n 8 = 8 = 9 8053 8 = 10 ) 11 documenting 13 relationship 12 the 13 relationship 13 relationship 14 between 13 relationship 20 identified 14 between 15 activity 15 activity 17 and 15 activity 19 were 16 restriction 17 and 17 and 18 depression 17 and 19 were 20 identified 21 for 20 identified 24 between 21 for 23 period 22 the 23 period 24 between 25 january 25 january 26 1980 27 and 28 june 28 june 29 2010 effect sizes were calculated as pearson [r] correlations using random - effects models . 0 ###LEFT-WALL### 2 sizes 0 ###LEFT-WALL### 4 calculated 0 ###LEFT-WALL### 14 . 1 effect 2 sizes 2 sizes 3 were 3 were 4 calculated 4 calculated 5 as 4 calculated 9 using 5 as 8 correlations 6 pearson 8 correlations 9 using 13 models 10 random 11 - 10 random 12 effects 12 effects 13 models the correlation between activity restriction and depression was positive and [of] large magnitude ( r = 0.39 ; 95 % ci , ..y 34 - 0.44 [ )( 0 ###LEFT-WALL### 2 correlation 0 ###LEFT-WALL### 8 was 0 ###LEFT-WALL### 18 ; 0 ###LEFT-WALL### 28 )( 1 the 2 correlation 2 correlation 3 between 2 correlation 8 was 3 between 6 and 4 activity 5 restriction 5 restriction 6 and 6 and 7 depression 8 was 13 magnitude 9 positive 10 and 10 and 12 large 10 and 13 magnitude 13 magnitude 16 = 14 ( 16 = 15 r 16 = 16 = 17 0.39 18 ; 21 ci 18 ; 22 , 19 95 21 ci 20 % 21 ci 22 , 23 ..y 22 , 25 - 23 ..y 24 34 24 34 25 - 25 - 26 0.44 activity restriction was most strongly correlated with depression in medical patients ( r = 0.45 ; 95 % ci , 0.42 - 0.48 ) , followed by caregivers ( r = 0.34 ; 95 % ci , 0.28 - 0.41 ) and community - dwelling adults [(] r = 0.28 ; 95 % ci , 0.25 - 0.31 [ )( 0 ###LEFT-WALL### 2 restriction 0 ###LEFT-WALL### 3 was 0 ###LEFT-WALL### 16 ; 0 ###LEFT-WALL### 60 )( 1 activity 2 restriction 2 restriction 3 was 3 was 4 most 4 most 6 correlated 4 most 7 with 4 most 14 = 5 strongly 6 correlated 7 with 8 depression 8 depression 9 in 9 in 11 patients 10 medical 11 patients 12 ( 14 = 13 r 14 = 14 = 15 0.45 16 ; 19 ci 16 ; 26 followed 16 ; 33 ; 17 95 19 ci 18 % 19 ci 19 ci 21 0.42 19 ci 26 followed 20 , 21 0.42 21 0.42 23 0.48 21 0.42 25 , 22 - 23 0.48 23 0.48 24 ) 26 followed 27 by 26 followed 28 caregivers 26 followed 31 = 29 ( 31 = 30 r 31 = 31 = 32 0.34 31 = 33 ; 33 ; 46 adults 33 ; 51 ; 34 95 46 adults 35 % 45 dwelling 36 ci 39 - 36 ci 42 and 37 , 39 - 38 0.28 39 - 39 - 40 0.41 39 - 41 ) 42 and 43 community 42 and 44 - 42 and 45 dwelling 45 dwelling 46 adults 46 adults 49 = 48 r 49 = 49 = 50 0.28 51 ; 54 ci 51 ; 55 , 52 95 54 ci 53 % 54 ci 55 , 56 0.25 55 , 57 - 56 0.25 57 - 57 - 58 0.31 activity [restriction] associated with medical conditions is a significant threat to well - being and quality of life , as well as to the lives of their caregivers . 0 ###LEFT-WALL### 1 activity 0 ###LEFT-WALL### 7 is 0 ###LEFT-WALL### 29 . 1 activity 3 associated 1 activity 7 is 3 associated 4 with 4 with 6 conditions 5 medical 6 conditions 7 is 10 threat 7 is 23 to 8 a 9 significant 8 a 10 threat 9 significant 10 threat 10 threat 11 to 10 threat 20 as 11 to 12 well 12 well 15 and 13 - 15 and 14 being 15 and 15 and 16 quality 15 and 17 of 15 and 19 , 17 of 18 life 20 as 21 well 22 as 23 to 23 to 25 lives 24 the 25 lives 25 lives 26 of 26 of 28 caregivers 27 their 28 caregivers assessment and treatment of activity restriction may be particularly helpful in preventing depression . 0 ###LEFT-WALL### 6 restriction 0 ###LEFT-WALL### 8 be 0 ###LEFT-WALL### 14 . 1 assessment 2 and 2 and 3 treatment 2 and 4 of 2 and 6 restriction 4 of 5 activity 6 restriction 7 may 7 may 8 be 8 be 10 helpful 9 particularly 10 helpful 10 helpful 11 in 11 in 12 preventing 12 preventing 13 depression ideal oncology drugs would be curative after a short treatment course if they could eliminate epithelium - originated carcinomas at their [non] [-] invasive , pre - malignant stages . 0 ###LEFT-WALL### 3 drugs 0 ###LEFT-WALL### 5 be 0 ###LEFT-WALL### 17 - 0 ###LEFT-WALL### 30 . 1 ideal 2 oncology 2 oncology 3 drugs 3 drugs 4 would 4 would 5 be 5 be 6 curative 6 curative 7 after 6 curative 12 if 7 after 11 course 8 a 11 course 9 short 10 treatment 10 treatment 11 course 12 if 13 they 12 if 15 eliminate 13 they 14 could 14 could 15 eliminate 15 eliminate 16 epithelium 17 - 19 carcinomas 18 originated 19 carcinomas 19 carcinomas 20 at 20 at 29 stages 21 their 29 stages 24 invasive 26 pre 24 invasive 27 - 24 invasive 29 stages 25 , 26 pre 26 pre 27 - 28 malignant 29 stages such ideal molecules , which are expected to molecularly abrogate all the instrumental mechanisms acquired by migrating cancer stem cells ( cscs ) to by [-] pass tumour suppressor barriers , might already exist . 0 ###LEFT-WALL### 3 molecules 0 ###LEFT-WALL### 34 exist 0 ###LEFT-WALL### 35 . 1 such 3 molecules 2 ideal 3 molecules 3 molecules 5 which 3 molecules 32 might 4 , 5 which 5 which 6 are 5 which 31 , 6 are 7 expected 7 expected 8 to 7 expected 10 abrogate 8 to 10 abrogate 9 molecularly 10 abrogate 10 abrogate 11 all 10 abrogate 25 by 11 all 14 mechanisms 11 all 24 to 12 the 14 mechanisms 13 instrumental 14 mechanisms 14 mechanisms 15 acquired 15 acquired 16 by 15 acquired 20 cells 15 acquired 24 to 16 by 17 migrating 18 cancer 20 cells 19 stem 20 cells 20 cells 22 cscs 21 ( 22 cscs 22 cscs 23 ) 25 by 30 barriers 27 pass 30 barriers 28 tumour 30 barriers 29 suppressor 30 barriers 32 might 34 exist 33 already 34 exist we [here] illustrate [how] system biology strategies for repositioning existing fda - approved drugs may accelerate our therapeutic capacity to eliminate csc traits in pre - invasive intraepithelial neoplasias . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 illustrate 0 ###LEFT-WALL### 12 - 1 we 3 illustrate 3 illustrate 7 strategies 3 illustrate 8 for 5 system 6 biology 6 biology 7 strategies 8 for 9 repositioning 9 repositioning 11 fda 10 existing 11 fda 12 - 14 drugs 12 - 21 eliminate 12 - 30 . 13 approved 14 drugs 14 drugs 15 may 15 may 16 accelerate 16 accelerate 19 capacity 16 accelerate 20 to 17 our 19 capacity 18 therapeutic 19 capacity 20 to 21 eliminate 21 eliminate 23 traits 21 eliminate 24 in 22 csc 23 traits 24 in 29 neoplasias 25 pre 26 - 25 pre 29 neoplasias 27 invasive 29 neoplasias 28 intraepithelial 29 neoplasias first , we describe a signalling network signature that overrides bioenergetics stress - and oncogene - induced senescence ( ois ) phenomena in cscs residing at pre - invasive lesions . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 describe 0 ###LEFT-WALL### 28 - 1 first 2 , 1 first 3 we 3 we 4 describe 4 describe 8 signature 5 a 8 signature 6 signalling 8 signature 7 network 8 signature 8 signature 9 that 8 signature 10 overrides 9 that 10 overrides 10 overrides 22 phenomena 10 overrides 23 in 10 overrides 26 at 11 bioenergetics 12 stress 12 stress 14 and 13 - 14 and 14 and 15 oncogene 14 and 18 senescence 14 and 22 phenomena 16 - 18 senescence 17 induced 18 senescence 18 senescence 20 ois 18 senescence 21 ) 19 ( 20 ois 20 ois 21 ) 23 in 24 cscs 24 cscs 25 residing 26 at 27 pre 28 - 30 lesions 28 - 31 . 29 invasive 30 lesions second , we functionally map the anti - malarial chloroquine and the anti - diabetic metformin ( " old drugs " ) to their recently recognized csc targets ( " new uses " ) within the network . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 5 map 0 ###LEFT-WALL### 38 . 1 second 2 , 1 second 3 we 3 we 5 map 4 functionally 5 map 5 map 11 and 5 map 23 to 5 map 35 within 6 the 10 chloroquine 7 anti 8 - 7 anti 10 chloroquine 9 malarial 10 chloroquine 10 chloroquine 11 and 11 and 16 metformin 11 and 20 drugs 12 the 16 metformin 13 anti 14 - 13 anti 16 metformin 15 diabetic 16 metformin 17 ( 18 " 17 ( 20 drugs 19 old 20 drugs 20 drugs 21 " 20 drugs 22 ) 23 to 28 targets 24 their 28 targets 25 recently 26 recognized 26 recognized 28 targets 27 csc 28 targets 28 targets 32 uses 29 ( 30 " 29 ( 32 uses 31 new 32 uses 32 uses 33 " 32 uses 34 ) 35 within 37 network 36 the 37 network by discussing the preclinical efficacy of chloroquine and metformin to inhibiting the genesis and self - renewal of cscs we finally underscore the expected translational impact of the " old drugs - new uses " repurposing strategy to open a new csc - targeted chemoprevention era . 0 ###LEFT-WALL### 20 we 0 ###LEFT-WALL### 22 underscore 0 ###LEFT-WALL### 43 - 0 ###LEFT-WALL### 47 . 1 by 2 discussing 1 by 20 we 2 discussing 5 efficacy 2 discussing 10 to 3 the 5 efficacy 4 preclinical 5 efficacy 5 efficacy 6 of 6 of 8 and 7 chloroquine 8 and 8 and 9 metformin 10 to 11 inhibiting 11 inhibiting 17 renewal 12 the 17 renewal 13 genesis 14 and 14 and 15 self 14 and 16 - 14 and 17 renewal 17 renewal 18 of 18 of 19 cscs 20 we 22 underscore 21 finally 22 underscore 22 underscore 26 impact 23 the 26 impact 24 expected 26 impact 25 translational 26 impact 26 impact 27 of 27 of 31 drugs 28 the 29 " 28 the 31 drugs 30 old 31 drugs 31 drugs 34 uses 32 - 34 uses 33 new 34 uses 34 uses 35 " 34 uses 36 repurposing 34 uses 43 - 36 repurposing 37 strategy 36 repurposing 38 to 38 to 39 open 39 open 42 csc 40 a 41 new 40 a 42 csc 41 new 42 csc 43 - 46 era 44 targeted 46 era 45 chemoprevention 46 era we report that α - tocotrienol quinone ( atq3 ) is a metabolite of α - tocotrienol , and that atq3 is a potent cellular protectant against oxidative stress and aging . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 32 . 1 we 2 report 2 report 19 and 3 that 7 quinone 3 that 11 is 3 that 19 and 4 α 5 - 4 α 6 tocotrienol 6 tocotrienol 7 quinone 7 quinone 9 atq3 7 quinone 11 is 8 ( 9 atq3 9 atq3 10 ) 11 is 13 metabolite 12 a 13 metabolite 13 metabolite 14 of 13 metabolite 17 tocotrienol 14 of 15 α 16 - 17 tocotrienol 17 tocotrienol 18 , 19 and 20 that 20 that 21 atq3 20 that 22 is 21 atq3 22 is 22 is 26 protectant 22 is 27 against 23 a 26 protectant 24 potent 26 protectant 25 cellular 26 protectant 27 against 30 and 28 oxidative 29 stress 29 stress 30 and 30 and 31 aging atq3 is orally bioavailable , crosses the blood - brain [barrier] , and has demonstrated clinical response [in] inherited mitochondrial disease in open label studies . 0 ###LEFT-WALL### 1 atq3 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 5 , 0 ###LEFT-WALL### 15 demonstrated 0 ###LEFT-WALL### 26 . 1 atq3 2 is 2 is 3 orally 2 is 4 bioavailable 5 , 13 and 6 crosses 8 blood 6 crosses 13 and 7 the 8 blood 8 blood 10 brain 9 - 10 brain 10 brain 12 , 13 and 14 has 14 has 15 demonstrated 15 demonstrated 21 disease 15 demonstrated 22 in 16 clinical 17 response 17 response 19 inherited 19 inherited 21 disease 20 mitochondrial 21 disease 22 in 25 studies 23 open 24 label 24 label 25 studies atq3 activity is dependent upon reversible 2e - redox - cycling . 0 ###LEFT-WALL### 2 activity 0 ###LEFT-WALL### 3 is 1 atq3 2 activity 2 activity 3 is 3 is 4 dependent 4 dependent 5 upon 5 upon 9 redox 6 reversible 9 redox 7 2e 8 - 7 2e 9 redox 9 redox 11 cycling 10 - 11 cycling 11 cycling 12 . atq3 may represent a broader class of unappreciated dietary - derived phytomolecular redox motifs that digitally encode biochemical data using redox state as a means to sense and transfer information essential [for] cellular function . 0 ###LEFT-WALL### 1 atq3 0 ###LEFT-WALL### 22 state 0 ###LEFT-WALL### 35 . 1 atq3 2 may 2 may 3 represent 3 represent 6 class 4 a 6 class 5 broader 6 class 6 class 7 of 7 of 13 redox 8 unappreciated 13 redox 9 dietary 10 - 9 dietary 13 redox 11 derived 13 redox 12 phytomolecular 13 redox 13 redox 14 motifs 13 redox 22 state 14 motifs 15 that 14 motifs 17 encode 14 motifs 22 state 15 that 17 encode 16 digitally 17 encode 17 encode 19 data 18 biochemical 19 data 19 data 20 using 20 using 21 redox 22 state 23 as 22 state 26 to 23 as 25 means 24 a 25 means 26 to 28 and 27 sense 28 and 28 and 34 function 29 transfer 34 function 30 information 34 function 31 essential 34 function 33 cellular 34 function background : n - acetylglucosamine ( glcnac ) and its derivates have been utilized in dietary supplements and for therapeutic development due to their unique characteristics . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 14 utilized 0 ###LEFT-WALL### 27 . 2 : 3 n 2 : 4 - 3 n 4 - 4 - 9 and 5 acetylglucosamine 7 glcnac 5 acetylglucosamine 9 and 6 ( 7 glcnac 7 glcnac 8 ) 9 and 11 derivates 9 and 12 have 10 its 11 derivates 12 have 13 been 13 been 14 utilized 14 utilized 18 and 14 utilized 23 to 15 in 17 supplements 15 in 18 and 16 dietary 17 supplements 18 and 19 for 19 for 21 development 20 therapeutic 21 development 22 due 23 to 23 to 26 characteristics 24 their 26 characteristics 25 unique 26 characteristics glcnac is recognized primarily for its function as a precursor to hyaluronic acid , which plays a significant role in the structure and hydration of the extracellular matrix in skin , in both the epidermis and the dermis . 0 ###LEFT-WALL### 1 glcnac 0 ###LEFT-WALL### 3 recognized 0 ###LEFT-WALL### 39 . 1 glcnac 2 is 2 is 3 recognized 3 recognized 4 primarily 3 recognized 8 as 3 recognized 11 to 3 recognized 32 in 4 primarily 5 for 5 for 7 function 6 its 7 function 8 as 10 precursor 9 a 10 precursor 11 to 13 acid 12 hyaluronic 13 acid 13 acid 15 which 14 , 15 which 15 which 16 plays 15 which 31 , 16 plays 19 role 16 plays 20 in 16 plays 29 in 17 a 18 significant 17 a 19 role 18 significant 19 role 20 in 23 and 21 the 22 structure 22 structure 23 and 23 and 24 hydration 23 and 25 of 25 of 28 matrix 26 the 28 matrix 27 extracellular 28 matrix 29 in 30 skin 32 in 36 and 33 both 36 and 34 the 35 epidermis 35 epidermis 36 and 36 and 38 dermis 37 the 38 dermis objective : we investigated the protective effects of glcnac on immortalized human skin fibroblasts ( hs68 ) against uvb damage . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 2 : 3 we 2 : 4 investigated 2 : 21 . 3 we 4 investigated 4 investigated 7 effects 4 investigated 10 on 4 investigated 18 against 5 the 7 effects 6 protective 7 effects 7 effects 8 of 8 of 9 glcnac 10 on 14 fibroblasts 11 immortalized 12 human 12 human 14 fibroblasts 13 skin 14 fibroblasts 14 fibroblasts 16 hs68 15 ( 16 hs68 16 hs68 17 ) 18 against 20 damage 19 uvb 20 damage we then explored the inhibitory effects of glcnac on uvb - induced collagenases and investigated the molecular mechanism underlying those effects . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 explored 0 ###LEFT-WALL### 11 - 0 ###LEFT-WALL### 22 . 1 we 3 explored 2 then 3 explored 3 explored 6 effects 3 explored 9 on 4 the 6 effects 5 inhibitory 6 effects 6 effects 7 of 7 of 8 glcnac 9 on 10 uvb 11 - 14 and 12 induced 13 collagenases 12 induced 14 and 14 and 15 investigated 15 investigated 18 mechanism 16 the 18 mechanism 17 molecular 18 mechanism 18 mechanism 19 underlying 19 underlying 21 effects 20 those 21 effects methods : those effects were assessed by semi - quantitative pcr , western blotting and enzymatic activity assays . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 4 effects 2 : 6 assessed 2 : 19 . 3 those 4 effects 4 effects 5 were 5 were 6 assessed 6 assessed 7 by 7 by 15 and 8 semi 9 - 8 semi 11 pcr 10 quantitative 11 pcr 11 pcr 12 , 12 , 14 blotting 12 , 15 and 13 western 14 blotting 15 and 18 assays 16 enzymatic 18 assays 17 activity 18 assays results : glcnac increased the viability [of] [,] and inhibited ros production in , hs68 cells exposed to uvb irradiation . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 1 results 2 : 2 : 3 glcnac 3 glcnac 9 and 3 glcnac 16 cells 4 increased 6 viability 4 increased 9 and 5 the 6 viability 9 and 10 inhibited 9 and 12 production 9 and 13 in 10 inhibited 11 ros 14 , 16 cells 15 hs68 16 cells 16 cells 17 exposed 16 cells 21 . 17 exposed 18 to 18 to 20 irradiation 19 uvb 20 irradiation pre - treatment of hs68 cells with glcnac inhibited uvb - induced production of the collagenases mmp - 1 and [mmp] - 13 . 0 ###LEFT-WALL### 1 pre 0 ###LEFT-WALL### 12 induced 0 ###LEFT-WALL### 24 . 1 pre 3 treatment 1 pre 12 induced 2 - 3 treatment 3 treatment 4 of 3 treatment 6 cells 3 treatment 9 inhibited 3 treatment 11 - 4 of 5 hs68 6 cells 7 with 6 cells 9 inhibited 7 with 8 glcnac 9 inhibited 10 uvb 12 induced 13 production 13 production 14 of 14 of 17 mmp 15 the 16 collagenases 16 collagenases 17 mmp 17 mmp 20 and 18 - 19 1 19 1 20 and 20 and 23 13 22 - 23 13 western blot analysis further revealed that glcnac markedly suppressed the enhancement of collagen degradation in uvb - exposed hs68 cells . 0 ###LEFT-WALL### 3 analysis 0 ###LEFT-WALL### 5 revealed 0 ###LEFT-WALL### 17 - 1 western 2 blot 2 blot 3 analysis 3 analysis 5 revealed 4 further 5 revealed 5 revealed 6 that 6 that 7 glcnac 6 that 9 suppressed 7 glcnac 9 suppressed 8 markedly 9 suppressed 9 suppressed 11 enhancement 9 suppressed 15 in 10 the 11 enhancement 11 enhancement 12 of 12 of 14 degradation 13 collagen 14 degradation 15 in 16 uvb 17 - 20 cells 17 - 21 . 18 exposed 20 cells 19 hs68 20 cells glcnac also suppressed uvb - induced activation of c - [jun] [,] c [-] fos and nf - κb and the phosphorylation of mapks and pi3k/akt , upstream modulators of ap - 1 and nf - κb . 0 ###LEFT-WALL### 1 glcnac 0 ###LEFT-WALL### 3 suppressed 0 ###LEFT-WALL### 5 - 1 glcnac 3 suppressed 2 also 3 suppressed 3 suppressed 4 uvb 5 - 7 activation 6 induced 7 activation 7 activation 8 of 8 of 20 and 9 c 10 - 10 - 13 c 10 - 19 κb 15 fos 16 and 16 and 17 nf 16 and 18 - 16 and 19 κb 19 κb 20 and 20 and 22 phosphorylation 20 and 23 of 21 the 22 phosphorylation 23 of 34 and 24 mapks 25 and 25 and 26 pi3k/akt 25 and 32 - 25 and 34 and 27 , 32 - 28 upstream 29 modulators 29 modulators 30 of 29 modulators 32 - 30 of 31 ap 32 - 33 1 34 and 35 nf 35 nf 37 κb 36 - 37 κb 37 κb 38 . moreover , glcnac decreased the uvb [-] induced influx of ca ( 2+ ) into hs68 cells and the phosphorylation of ca ( 2+ )/calmodulin - dependent kinases ( camks ) . 0 ###LEFT-WALL### 3 glcnac 0 ###LEFT-WALL### 4 decreased 0 ###LEFT-WALL### 32 . 1 moreover 2 , 1 moreover 3 glcnac 3 glcnac 4 decreased 4 decreased 18 and 5 the 9 influx 6 uvb 8 induced 8 induced 9 influx 9 influx 10 of 9 influx 15 into 9 influx 18 and 10 of 11 ca 11 ca 13 2+ 12 ( 13 2+ 13 2+ 14 ) 15 into 17 cells 16 hs68 17 cells 18 and 20 phosphorylation 18 and 21 of 19 the 20 phosphorylation 21 of 22 ca 22 ca 28 kinases 23 ( 28 kinases 24 2+ 28 kinases 25 )/calmodulin 26 - 25 )/calmodulin 27 dependent 27 dependent 28 kinases 28 kinases 30 camks 28 kinases 31 ) 29 ( 30 camks 30 camks 31 ) conclusion : the results indicate that glcnac inhibited uvb - induced collagenolytic mmp production by interfering with ca ( 2+ ) - dependent akt and mapks/ap - 1 and nf - κb signaling . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 4 results 2 : 5 indicate 2 : 10 - 3 the 4 results 4 results 5 indicate 5 indicate 6 that 6 that 7 glcnac 6 that 8 inhibited 7 glcnac 8 inhibited 8 inhibited 9 uvb 10 - 29 and 11 induced 14 production 12 collagenolytic 14 production 13 mmp 14 production 14 production 15 by 14 production 29 and 15 by 16 interfering 16 interfering 17 with 17 with 18 ca 17 with 28 1 18 ca 20 2+ 18 ca 25 and 19 ( 20 2+ 20 2+ 21 ) 22 - 25 and 23 dependent 24 akt 24 akt 25 and 25 and 26 mapks/ap 25 and 27 - 29 and 30 nf 29 and 31 - 29 and 32 κb 31 - 32 κb 32 κb 33 signaling 32 κb 34 . they may thus be potentially useful in the prevention and treatment of skin photoaging . 0 ###LEFT-WALL### 1 they 0 ###LEFT-WALL### 4 be 0 ###LEFT-WALL### 15 . 1 they 2 may 2 may 4 be 3 thus 4 be 4 be 5 potentially 4 be 6 useful 6 useful 7 in 7 in 10 and 8 the 9 prevention 9 prevention 10 and 10 and 11 treatment 10 and 12 of 12 of 14 photoaging 13 skin 14 photoaging diffusion tensor and structural mri images were acquired on ninety - six patients with schizophrenia ( 69 men and 27 women ) between the ages of 18 and 79 ( mean=39.83 , sd=15.16 dsm - iv diagnosis of schizophrenia according to the comprehensive assessment of symptoms and history ) . 0 ###LEFT-WALL### 5 mri 0 ###LEFT-WALL### 8 acquired 0 ###LEFT-WALL### 50 . 1 diffusion 5 mri 2 tensor 3 and 3 and 4 structural 3 and 5 mri 5 mri 6 images 5 mri 7 were 5 mri 8 acquired 6 images 7 were 8 acquired 9 on 8 acquired 13 patients 8 acquired 14 with 9 on 10 ninety 11 - 12 six 12 six 13 patients 14 with 15 schizophrenia 14 with 23 between 15 schizophrenia 19 and 16 ( 19 and 17 69 18 men 18 men 19 and 19 and 21 women 19 and 22 ) 20 27 21 women 23 between 25 ages 24 the 25 ages 25 ages 26 of 25 ages 37 diagnosis 26 of 28 and 27 18 28 and 28 and 29 79 28 and 31 mean=39.83 28 and 34 dsm 30 ( 31 mean=39.83 31 mean=39.83 32 , 32 , 34 dsm 33 sd=15.16 34 dsm 34 dsm 35 - 35 - 37 diagnosis 36 iv 37 diagnosis 37 diagnosis 38 of 37 diagnosis 40 according 37 diagnosis 49 ) 38 of 39 schizophrenia 40 according 41 to 40 according 44 assessment 41 to 43 comprehensive 42 the 43 comprehensive 44 assessment 45 of 45 of 47 and 46 symptoms 47 and 47 and 48 history the patients reported a mean age [of] onset of 23 years ( range=13 - 38 , sd=6 ) . 0 ###LEFT-WALL### 2 patients 0 ###LEFT-WALL### 3 reported 0 ###LEFT-WALL### 19 . 1 the 2 patients 2 patients 3 reported 3 reported 8 onset 4 a 5 mean 4 a 8 onset 5 mean 6 age 6 age 8 onset 8 onset 9 of 8 onset 13 range=13 8 onset 15 38 9 of 11 years 10 23 11 years 12 ( 13 range=13 13 range=13 14 - 14 - 15 38 15 38 17 sd=6 15 38 18 ) 16 , 17 sd=6 17 sd=6 18 ) patients were divided into an acute subgroup ( duration ≤3 years , n=25 ) , and a chronic subgroup ( duration >3 years , n=64 ) . 0 ###LEFT-WALL### 1 patients 0 ###LEFT-WALL### 3 divided 0 ###LEFT-WALL### 27 . 1 patients 2 were 2 were 3 divided 3 divided 4 into 4 into 7 subgroup 5 an 6 acute 5 an 7 subgroup 6 acute 7 subgroup 7 subgroup 16 and 8 ( 16 and 9 duration 10 ≤3 10 ≤3 11 years 11 years 13 n=25 11 years 16 and 12 , 13 n=25 13 n=25 14 ) 15 , 16 and 16 and 19 subgroup 16 and 23 years 16 and 25 n=64 16 and 26 ) 17 a 18 chronic 17 a 19 subgroup 18 chronic 19 subgroup 20 ( 23 years 21 duration 22 >3 22 >3 23 years 23 years 24 , 24 , 25 n=64 25 n=64 26 ) ninety - three mentally normal comparison subjects were recruited ; 55 men and 38 women between the ages of 18 and 82 ( mean=35.77 , sd=18.12 ) . 0 ###LEFT-WALL### 7 subjects 0 ###LEFT-WALL### 9 recruited 0 ###LEFT-WALL### 10 ; 0 ###LEFT-WALL### 28 . 1 ninety 2 - 2 - 3 three 2 - 7 subjects 4 mentally 5 normal 5 normal 6 comparison 6 comparison 7 subjects 7 subjects 8 were 8 were 9 recruited 10 ; 13 and 11 55 12 men 12 men 13 and 13 and 15 women 14 38 15 women 15 women 16 between 16 between 18 ages 17 the 18 ages 18 ages 19 of 18 ages 24 mean=35.77 18 ages 26 sd=18.12 19 of 21 and 20 18 21 and 21 and 22 82 23 ( 24 mean=35.77 24 mean=35.77 25 , 25 , 26 sd=18.12 26 sd=18.12 27 ) the mri images were segmented by brodmann area , and the fractional anisotropy ( fa ) for the white matter within each brodmann area was calculated . 0 ###LEFT-WALL### 3 images 0 ###LEFT-WALL### 5 segmented 0 ###LEFT-WALL### 26 calculated 0 ###LEFT-WALL### 27 . 1 the 3 images 2 mri 3 images 3 images 4 were 4 were 5 segmented 5 segmented 6 by 5 segmented 17 for 5 segmented 21 within 6 by 10 and 7 brodmann 8 area 8 area 10 and 9 , 10 and 10 and 13 anisotropy 10 and 15 fa 11 the 13 anisotropy 12 fractional 13 anisotropy 14 ( 15 fa 15 fa 16 ) 17 for 20 matter 18 the 20 matter 19 white 20 matter 21 within 22 each 23 brodmann 24 area 23 brodmann 25 was 23 brodmann 26 calculated 24 area 25 was the fa in white matter was decreased in patients with schizophrenia broadly across the entire brain , but to a greater extent in white matter underneath frontal , temporal and cingulate cortical areas . 0 ###LEFT-WALL### 2 fa 0 ###LEFT-WALL### 7 decreased 0 ###LEFT-WALL### 34 . 1 the 2 fa 2 fa 3 in 2 fa 5 matter 2 fa 6 was 2 fa 7 decreased 3 in 4 white 5 matter 6 was 7 decreased 8 in 7 decreased 10 with 7 decreased 12 broadly 7 decreased 18 but 7 decreased 23 in 8 in 9 patients 10 with 11 schizophrenia 13 across 16 brain 13 across 18 but 14 the 16 brain 15 entire 16 brain 17 , 18 but 18 but 19 to 19 to 22 extent 20 a 22 extent 21 greater 22 extent 23 in 25 matter 24 white 25 matter 25 matter 26 underneath 26 underneath 33 areas 27 frontal 28 , 28 , 29 temporal 28 , 30 and 30 and 31 cingulate 30 and 33 areas 32 cortical 33 areas both normals and patients with schizophrenia showed a decrease in anisotropy with age but patients with schizophrenia showed a significantly greater rate of decrease in fa in brodmann area 10 bilaterally , 11 in the left hemisphere and 34 in [the] right hemisphere . 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 7 showed 0 ###LEFT-WALL### 32 , 0 ###LEFT-WALL### 44 . 1 both 2 normals 2 normals 3 and 3 and 4 patients 3 and 5 with 3 and 7 showed 5 with 6 schizophrenia 7 showed 9 decrease 7 showed 18 showed 8 a 9 decrease 9 decrease 10 in 9 decrease 14 but 9 decrease 18 showed 10 in 11 anisotropy 11 anisotropy 12 with 12 with 13 age 14 but 15 patients 15 patients 16 with 16 with 17 schizophrenia 18 showed 22 rate 18 showed 29 area 18 showed 31 bilaterally 19 a 22 rate 20 significantly 21 greater 21 greater 22 rate 22 rate 23 of 23 of 24 decrease 24 decrease 25 in 24 decrease 27 in 25 in 26 fa 27 in 28 brodmann 29 area 30 10 32 , 43 hemisphere 33 11 34 in 34 in 43 hemisphere 35 the 37 hemisphere 36 left 37 hemisphere 37 hemisphere 38 and 38 and 42 right 38 and 43 hemisphere 39 34 40 in 40 in 42 right objectives : this study aimed to identify participant characteristics associated with volunteering among older adults . 0 ###LEFT-WALL### 1 objectives 0 ###LEFT-WALL### 2 : 2 : 4 study 2 : 5 aimed 2 : 16 . 3 this 4 study 4 study 5 aimed 5 aimed 6 to 5 aimed 7 identify 6 to 7 identify 7 identify 9 characteristics 7 identify 11 with 8 participant 9 characteristics 9 characteristics 10 associated 11 with 12 volunteering 12 volunteering 13 among 13 among 15 adults 14 older 15 adults methods : based on data from the 2008 aging texas well ( atw ) indicators survey , we examined the degree to which demographic factors , health status , spiritual participation , and community involvement are associated with volunteering among adults aged 60 years or older ( n = 525 ) . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 18 we 2 : 19 examined 2 : 52 . 3 based 4 on 3 based 6 from 3 based 17 , 3 based 18 we 4 on 5 data 6 from 16 survey 7 the 16 survey 8 2008 10 texas 9 aging 10 texas 10 texas 11 well 11 well 13 atw 12 ( 13 atw 13 atw 14 ) 13 atw 15 indicators 15 indicators 16 survey 18 we 19 examined 19 examined 21 degree 19 examined 42 aged 20 the 21 degree 21 degree 22 to 21 degree 42 aged 22 to 23 which 22 to 33 and 22 to 37 associated 24 demographic 25 factors 25 factors 26 , 26 , 28 status 26 , 29 , 27 health 28 status 29 , 31 participation 29 , 33 and 30 spiritual 31 participation 32 , 33 and 33 and 35 involvement 33 and 36 are 34 community 35 involvement 36 are 37 associated 37 associated 38 with 37 associated 40 among 38 with 39 volunteering 40 among 41 adults 42 aged 45 or 43 60 44 years 44 years 45 or 45 or 46 older 45 or 49 = 47 ( 49 = 48 n 49 = 49 = 50 525 49 = 51 ) results : rates of volunteering varied by race/ethnicity [:] [non] - hispanic whites ( 56.4 % ) , african americans ( 51.1 % ) , and hispanics ( 43.2 % ) . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 26 and 2 : 32 . 3 rates 4 of 3 rates 6 varied 3 rates 26 and 4 of 5 volunteering 6 varied 7 by 7 by 8 race/ethnicity 8 race/ethnicity 13 whites 8 race/ethnicity 20 americans 11 - 13 whites 12 hispanic 13 whites 13 whites 16 % 13 whites 18 , 14 ( 16 % 15 56.4 16 % 16 % 17 ) 18 , 20 americans 19 african 20 americans 20 americans 23 % 20 americans 24 ) 21 ( 23 % 22 51.1 23 % 23 % 24 ) 25 , 26 and 26 and 27 hispanics 26 and 30 % 28 ( 30 % 29 43.2 30 % 30 % 31 ) bivariate analyses showed that [non] - hispanic white older adults were more likely to participate in formal volunteering activities , while their african american and hispanic counterparts tended to participate in informal volunteering activities . 0 ###LEFT-WALL### 2 analyses 0 ###LEFT-WALL### 3 showed 0 ###LEFT-WALL### 6 - 1 bivariate 2 analyses 2 analyses 3 showed 3 showed 4 that 6 - 7 hispanic 6 - 11 were 6 - 20 , 6 - 35 . 7 hispanic 11 were 8 white 10 adults 9 older 10 adults 10 adults 11 were 11 were 13 likely 12 more 13 likely 13 likely 14 to 13 likely 15 participate 14 to 15 participate 15 participate 16 in 16 in 19 activities 17 formal 19 activities 18 volunteering 19 activities 20 , 30 participate 21 while 27 counterparts 21 while 30 participate 22 their 24 american 23 african 24 american 24 american 25 and 25 and 26 hispanic 25 and 27 counterparts 27 counterparts 29 to 28 tended 29 to 30 participate 31 in 31 in 34 activities 32 informal 34 activities 33 volunteering 34 activities logistic regression analyses revealed that volunteering was less observed among hispanics ( or = 0.48 , 95 % ci 0.29 - 0.78 ) . 0 ###LEFT-WALL### 3 analyses 0 ###LEFT-WALL### 9 observed 0 ###LEFT-WALL### 24 . 1 logistic 3 analyses 2 regression 3 analyses 3 analyses 4 revealed 3 analyses 5 that 3 analyses 7 was 3 analyses 9 observed 5 that 6 volunteering 5 that 7 was 6 volunteering 7 was 7 was 8 less 9 observed 10 among 9 observed 15 0.48 10 among 13 or 11 hispanics 13 or 12 ( 13 or 14 = 15 0.48 15 0.48 19 ci 16 , 19 ci 17 95 19 ci 18 % 19 ci 19 ci 21 - 19 ci 23 ) 20 0.29 21 - 21 - 22 0.78 conclusions : given the positive associations of mental health , spirituality , and social engagement with volunteering among older adults , system - level efforts to increase the sense [of] community among older adults and recognize their roles as volunteers will be helpful in recruiting and retaining older volunteers . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 3 given 0 ###LEFT-WALL### 21 , 0 ###LEFT-WALL### 50 . 1 conclusions 2 : 2 : 3 given 3 given 6 associations 4 the 6 associations 5 positive 6 associations 6 associations 7 of 7 of 13 and 8 mental 9 health 9 health 10 , 10 , 11 spirituality 10 , 13 and 12 , 13 and 13 and 15 engagement 13 and 21 , 14 social 15 engagement 15 engagement 16 with 16 with 17 volunteering 17 volunteering 18 among 18 among 20 adults 19 older 20 adults 21 , 22 system 21 , 23 - 23 - 25 efforts 23 - 42 be 24 level 25 efforts 25 efforts 26 to 25 efforts 35 and 25 efforts 41 will 26 to 35 and 27 increase 31 community 27 increase 32 among 27 increase 35 and 28 the 31 community 29 sense 31 community 32 among 34 adults 33 older 34 adults 35 and 36 recognize 35 and 38 roles 37 their 38 roles 38 roles 39 as 39 as 40 volunteers 41 will 42 be 42 be 49 volunteers 43 helpful 44 in 43 helpful 46 and 44 in 45 recruiting 46 and 47 retaining 46 and 49 volunteers 48 older 49 volunteers [a] wealth of published studies [indicate] that a variety [of] chemokines are actively secreted by the prostatic microenvironment consequent to disruptions in normal tissue homeostasis due to the aging process or inflammatory responses . 0 ###LEFT-WALL### 31 or 0 ###LEFT-WALL### 34 . 2 wealth 3 of 2 wealth 31 or 3 of 5 studies 4 published 5 studies 5 studies 7 that 5 studies 14 secreted 7 that 9 variety 7 that 14 secreted 8 a 9 variety 9 variety 11 chemokines 9 variety 12 are 9 variety 14 secreted 11 chemokines 12 are 13 actively 14 secreted 14 secreted 15 by 14 secreted 22 in 14 secreted 27 to 15 by 18 microenvironment 16 the 18 microenvironment 17 prostatic 18 microenvironment 18 microenvironment 19 consequent 19 consequent 20 to 20 to 21 disruptions 22 in 25 homeostasis 23 normal 25 homeostasis 24 tissue 25 homeostasis 26 due 27 to 27 to 30 process 28 the 30 process 29 aging 30 process 31 or 33 responses 32 inflammatory 33 responses the accumulation of senescent stromal fibroblasts , and , possibly , epithelial cells , may serve as potential driving forces behind chemokine secretion in the aging and enlarged human prostate . 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 16 serve 0 ###LEFT-WALL### 31 . 1 the 2 accumulation 2 accumulation 3 of 2 accumulation 8 and 3 of 6 fibroblasts 4 senescent 6 fibroblasts 5 stromal 6 fibroblasts 7 , 8 and 8 and 10 possibly 8 and 13 cells 8 and 14 , 8 and 15 may 9 , 10 possibly 10 possibly 11 , 12 epithelial 13 cells 15 may 16 serve 16 serve 20 forces 16 serve 24 in 17 as 18 potential 18 potential 20 forces 19 driving 20 forces 20 forces 21 behind 21 behind 23 secretion 22 chemokine 23 secretion 24 in 27 and 25 the 26 aging 26 aging 27 and 27 and 30 prostate 28 enlarged 30 prostate 29 human 30 prostate chronic prostatitis/chronic pelvic pain syndrome ( [cp/cpps] [ )(and histological inflammation may also potentially serve as rich sources of chemokine secretion in the prostate . 0 ###LEFT-WALL### 5 syndrome 0 ###LEFT-WALL### 9 )(and 0 ###LEFT-WALL### 25 . 1 chronic 4 pain 2 prostatitis/chronic 4 pain 3 pelvic 4 pain 4 pain 5 syndrome 6 ( 9 )(and 9 )(and 11 inflammation 9 )(and 15 serve 10 histological 11 inflammation 11 inflammation 12 may 12 may 15 serve 13 also 15 serve 14 potentially 15 serve 15 serve 18 sources 15 serve 22 in 16 as 17 rich 17 rich 18 sources 18 sources 19 of 19 of 21 secretion 20 chemokine 21 secretion 22 in 24 prostate 23 the 24 prostate once bound to their cognate receptors , chemokines can stimulate powerful [pro] - proliferation signal transduction pathways and thus function as potent growth factors in the development and progression of benign prostatic hyperplasia ( bph ) and lower urinary tract symptoms ( luts ) . 0 ###LEFT-WALL### 7 , 0 ###LEFT-WALL### 45 . 1 once 7 , 2 bound 3 to 2 bound 7 , 3 to 6 receptors 4 their 6 receptors 5 cognate 6 receptors 7 , 10 stimulate 8 chemokines 9 can 9 can 10 stimulate 10 stimulate 18 and 10 stimulate 21 as 11 powerful 13 - 11 powerful 14 proliferation 14 proliferation 17 pathways 15 signal 17 pathways 16 transduction 17 pathways 17 pathways 18 and 18 and 19 thus 18 and 20 function 21 as 28 and 22 potent 24 factors 23 growth 24 factors 24 factors 25 in 24 factors 28 and 25 in 27 development 26 the 27 development 28 and 29 progression 28 and 30 of 28 and 43 luts 30 of 37 and 31 benign 32 prostatic 32 prostatic 33 hyperplasia 33 hyperplasia 35 bph 34 ( 35 bph 35 bph 36 ) 35 bph 37 and 37 and 41 symptoms 38 lower 40 tract 39 urinary 40 tract 40 tract 41 symptoms 42 ( 43 luts 43 luts 44 ) these functions have been amply demonstrated experimentally and particularly point to robust mitogen activated protein kinase ( mapk ) and phosphoinositide 3 - [kinase] ( pi3k ) signaling , as well as global transcriptional responses , which mediate chemokine - stimulated cellular proliferative responses . 0 ###LEFT-WALL### 2 functions 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 23 - 0 ###LEFT-WALL### 45 . 1 these 2 functions 2 functions 8 and 3 have 4 been 3 have 8 and 4 been 6 demonstrated 5 amply 6 demonstrated 6 demonstrated 7 experimentally 8 and 10 point 8 and 11 to 9 particularly 10 point 11 to 20 and 12 robust 18 mapk 13 mitogen 14 activated 14 activated 15 protein 15 protein 16 kinase 16 kinase 18 mapk 17 ( 18 mapk 18 mapk 19 ) 18 mapk 20 and 20 and 21 phosphoinositide 21 phosphoinositide 22 3 23 - 35 responses 23 - 41 stimulated 25 ( 26 pi3k 26 pi3k 27 ) 26 pi3k 35 responses 28 signaling 29 , 28 signaling 35 responses 30 as 31 well 30 as 35 responses 32 as 33 global 33 global 35 responses 34 transcriptional 35 responses 35 responses 37 which 35 responses 41 stimulated 36 , 37 which 37 which 38 mediate 37 which 40 - 38 mediate 39 chemokine 41 stimulated 44 responses 42 cellular 44 responses 43 proliferative 44 responses a small body of literature also suggests that chemokine - mediated angiogenesis may comprise a contributing factor to bph/luts development and progression . 0 ###LEFT-WALL### 3 body 0 ###LEFT-WALL### 7 suggests 0 ###LEFT-WALL### 10 - 1 a 2 small 1 a 3 body 2 small 3 body 3 body 4 of 3 body 7 suggests 4 of 5 literature 6 also 7 suggests 7 suggests 9 chemokine 8 that 9 chemokine 10 - 12 angiogenesis 10 - 14 comprise 10 - 23 . 11 mediated 12 angiogenesis 12 angiogenesis 13 may 13 may 14 comprise 14 comprise 17 factor 14 comprise 18 to 15 a 17 factor 16 contributing 17 factor 18 to 21 and 19 bph/luts 20 development 20 development 21 and 21 and 22 progression thus , the observed low - level secretion of multiple chemokines within the aging prostatic microenvironment may promote a concomitant low - level , but cumulative , over [-] proliferation [of] both stromal fibroblastic and epithelial cell types associated with increased prostatic volume . 0 ###LEFT-WALL### 8 secretion 0 ###LEFT-WALL### 18 promote 1 thus 2 , 1 thus 8 secretion 3 the 8 secretion 4 observed 8 secretion 5 low 6 - 5 low 8 secretion 7 level 8 secretion 8 secretion 9 of 8 secretion 17 may 9 of 11 chemokines 10 multiple 11 chemokines 11 chemokines 12 within 12 within 16 microenvironment 13 the 16 microenvironment 14 aging 16 microenvironment 15 prostatic 16 microenvironment 17 may 18 promote 18 promote 21 low 18 promote 28 over 19 a 21 low 20 concomitant 21 low 21 low 25 but 22 - 25 but 23 level 25 but 24 , 25 but 25 but 26 cumulative 25 but 27 , 27 , 28 over 28 over 38 types 28 over 44 . 30 proliferation 37 cell 32 both 33 stromal 33 stromal 37 cell 34 fibroblastic 35 and 35 and 36 epithelial 35 and 37 cell 37 cell 38 types 38 types 39 associated 39 associated 40 with 40 with 43 volume 41 increased 43 volume 42 prostatic 43 volume though the accumulated evidence is far from complete and suffers from some rather extensive gaps in knowledge , it argues favorably for the conclusion that chemokines can , and likely do , promote prostatic enlargement and the associated lower urinary tract symptoms , and justifies further investigations examining chemokines as potential therapeutic targets to delay or ablate bph/luts initiation and progression . 0 ###LEFT-WALL### 4 evidence 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 18 , 0 ###LEFT-WALL### 62 . 1 though 4 evidence 2 the 4 evidence 3 accumulated 4 evidence 4 evidence 9 and 5 is 8 complete 5 is 9 and 6 far 7 from 7 from 8 complete 9 and 10 suffers 9 and 11 from 11 from 15 gaps 12 some 15 gaps 13 rather 14 extensive 14 extensive 15 gaps 15 gaps 16 in 16 in 17 knowledge 18 , 19 it 18 , 29 and 18 , 32 , 19 it 29 and 20 argues 21 favorably 20 argues 22 for 20 argues 25 that 20 argues 29 and 22 for 24 conclusion 23 the 24 conclusion 25 that 26 chemokines 25 that 27 can 26 chemokines 27 can 28 , 29 and 29 and 31 do 30 likely 31 do 32 , 44 and 33 promote 36 and 33 promote 44 and 34 prostatic 35 enlargement 35 enlargement 36 and 36 and 42 symptoms 36 and 43 , 37 the 42 symptoms 38 associated 41 tract 39 lower 41 tract 40 urinary 41 tract 41 tract 42 symptoms 44 and 56 or 45 justifies 46 further 45 justifies 49 chemokines 45 justifies 56 or 47 investigations 49 chemokines 48 examining 49 chemokines 49 chemokines 50 as 49 chemokines 54 to 49 chemokines 55 delay 50 as 53 targets 51 potential 53 targets 52 therapeutic 53 targets 54 to 55 delay 56 or 57 ablate 57 ablate 60 and 58 bph/luts 59 initiation 59 initiation 60 and 60 and 61 progression unlabelled : substantial data have accumulated over the past decade indicating that the adult brain is capable of substantial [structural] and functional reorganization [after] stroke . 0 ###LEFT-WALL### 1 unlabelled 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 26 . 2 : 3 substantial 3 substantial 4 data 3 substantial 6 accumulated 3 substantial 18 of 4 data 5 have 5 have 6 accumulated 6 accumulated 7 over 7 over 10 decade 8 the 10 decade 9 past 10 decade 10 decade 11 indicating 11 indicating 12 that 12 that 15 brain 12 that 16 is 13 the 15 brain 14 adult 15 brain 15 brain 16 is 16 is 17 capable 18 of 21 and 19 substantial 21 and 21 and 25 stroke 22 functional 23 reorganization 23 reorganization 25 stroke while some limited recovery is known to occur spontaneously , especially within the first month post - stroke , there is currently significant optimism that new interventions based on the modulation of neuroplasticity mechanisms will provide greater functional benefits in a larger population of stroke survivors . 0 ###LEFT-WALL### 4 recovery 0 ###LEFT-WALL### 6 known 0 ###LEFT-WALL### 17 - 1 while 2 some 1 while 4 recovery 2 some 3 limited 4 recovery 5 is 5 is 6 known 6 known 7 to 6 known 8 occur 7 to 8 occur 8 occur 9 spontaneously 8 occur 12 within 10 , 11 especially 10 , 12 within 12 within 16 post 12 within 17 - 13 the 14 first 13 the 16 post 15 month 16 post 17 - 18 stroke 17 - 19 , 17 - 47 . 19 , 20 there 19 , 21 is 20 there 21 is 21 is 22 currently 21 is 24 optimism 21 is 29 on 23 significant 24 optimism 24 optimism 25 that 24 optimism 28 based 25 that 27 interventions 25 that 28 based 26 new 27 interventions 27 interventions 28 based 29 on 31 modulation 30 the 31 modulation 31 modulation 32 of 31 modulation 34 mechanisms 31 modulation 36 provide 32 of 33 neuroplasticity 34 mechanisms 35 will 35 will 36 provide 36 provide 39 benefits 37 greater 39 benefits 38 functional 39 benefits 39 benefits 40 in 39 benefits 44 of 40 in 43 population 41 a 43 population 42 larger 43 population 44 of 46 survivors 45 stroke 46 survivors to place this information in the context of current thinking about brain plasticity , this review outlines the basic theories of why spontaneous recovery occurs , and introduces important principles to explain the effects of post - stroke behavioral experience on neural plasticity . 0 ###LEFT-WALL### 1 to 0 ###LEFT-WALL### 14 , 0 ###LEFT-WALL### 37 - 0 ###LEFT-WALL### 44 . 1 to 14 , 2 place 4 information 2 place 14 , 3 this 4 information 4 information 5 in 4 information 8 of 5 in 7 context 6 the 7 context 8 of 10 thinking 9 current 10 thinking 10 thinking 11 about 11 about 13 plasticity 12 brain 13 plasticity 14 , 32 explain 15 this 16 review 16 review 27 and 17 outlines 20 theories 17 outlines 27 and 18 the 20 theories 19 basic 20 theories 20 theories 21 of 21 of 22 why 22 why 24 recovery 22 why 25 occurs 23 spontaneous 24 recovery 24 recovery 25 occurs 26 , 27 and 27 and 28 introduces 27 and 31 to 28 introduces 30 principles 29 important 30 principles 31 to 32 explain 32 explain 34 effects 33 the 34 effects 34 effects 35 of 35 of 36 post 37 - 38 stroke 38 stroke 40 experience 39 behavioral 40 experience 40 experience 41 on 41 on 43 plasticity 42 neural 43 plasticity learning outcomes : readers will be able to : ( [a] [ )(explain the three classic theories to explain spontaneous recovery after focal brain injury [,] ( [b] [ )(explain the neurophysiological effects of post [-] injury rehabilitative therapy on functional organization in motor cortex [,] [(] [c] [ )(readers will be able to describe some of the variables that impact the effects of post - stroke behavioral experience on neuroplasticity , and [(] [d] [ )(readers will be able to explain some of the current laboratory - based approaches [to] modifying brain circuits after stroke that might soon be translated to human application . 0 ###LEFT-WALL### 2 outcomes 0 ###LEFT-WALL### 3 : 0 ###LEFT-WALL### 9 : 1 learning 2 outcomes 3 : 4 readers 4 readers 5 will 4 readers 8 to 4 readers 9 : 5 will 6 be 6 be 7 able 7 able 8 to 9 : 18 to 10 ( 13 )(explain 13 )(explain 17 theories 13 )(explain 18 to 14 the 17 theories 15 three 17 theories 16 classic 17 theories 18 to 19 explain 19 explain 21 recovery 19 explain 22 after 20 spontaneous 21 recovery 22 after 24 brain 23 focal 24 brain 24 brain 25 injury 24 brain 33 effects 24 brain 34 of 25 injury 33 effects 27 ( 30 )(explain 30 )(explain 32 neurophysiological 30 )(explain 33 effects 31 the 32 neurophysiological 34 of 39 therapy 35 post 37 injury 37 injury 39 therapy 38 rehabilitative 39 therapy 39 therapy 40 on 40 on 42 organization 41 functional 42 organization 42 organization 43 in 42 organization 53 able 43 in 45 cortex 44 motor 45 cortex 45 cortex 50 )(readers 45 cortex 52 be 50 )(readers 51 will 51 will 52 be 53 able 54 to 53 able 55 describe 54 to 55 describe 55 describe 56 some 56 some 57 of 56 some 60 that 56 some 61 impact 57 of 59 variables 58 the 59 variables 60 that 61 impact 61 impact 73 and 62 the 63 effects 63 effects 64 of 63 effects 73 and 64 of 65 post 65 post 69 experience 66 - 69 experience 67 stroke 69 experience 68 behavioral 69 experience 69 experience 70 on 69 experience 72 , 70 on 71 neuroplasticity 72 , 73 and 73 and 77 )(readers 73 and 78 will 73 and 82 explain 78 will 79 be 79 be 80 able 80 able 81 to 80 able 82 explain 81 to 82 explain 82 explain 83 some 83 some 84 of 83 some 94 circuits 84 of 87 laboratory 85 the 87 laboratory 86 current 87 laboratory 88 - 94 circuits 89 based 93 brain 90 approaches 93 brain 92 modifying 93 brain 93 brain 94 circuits 94 circuits 95 after 94 circuits 97 that 94 circuits 98 might 94 circuits 105 . 95 after 96 stroke 97 that 98 might 98 might 100 be 99 soon 100 be 100 be 101 translated 101 translated 102 to 102 to 104 application 103 human 104 application risk stratification models are effective tools for the management of cardiovascular diseases . 0 ###LEFT-WALL### 3 models 0 ###LEFT-WALL### 4 are 0 ###LEFT-WALL### 13 . 1 risk 3 models 2 stratification 3 models 3 models 4 are 4 are 6 tools 5 effective 6 tools 6 tools 7 for 7 for 9 management 8 the 9 management 9 management 10 of 10 of 12 diseases 11 cardiovascular 12 diseases although several risk scores have been proposed , the relevance and superiority of these predictive models have not been fully validated in an independent and nonclinical trial - based population . 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 21 validated 0 ###LEFT-WALL### 28 - 0 ###LEFT-WALL### 31 . 1 although 4 scores 1 although 7 proposed 1 although 11 and 2 several 4 scores 3 risk 4 scores 4 scores 5 have 5 have 6 been 6 been 7 proposed 7 proposed 8 , 9 the 10 relevance 10 relevance 11 and 11 and 12 superiority 11 and 13 of 11 and 17 have 13 of 16 models 14 these 16 models 15 predictive 16 models 17 have 18 not 17 have 19 been 19 been 21 validated 20 fully 21 validated 21 validated 22 in 22 in 25 and 23 an 24 independent 24 independent 25 and 25 and 27 trial 26 nonclinical 27 trial 28 - 30 population 29 based 30 population we studied 2,472 consecutive patients initially hospitalized in our institution from april 2004 to december 2009 . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 studied 0 ###LEFT-WALL### 17 . 1 we 2 studied 2 studied 5 patients 3 2,472 5 patients 4 consecutive 5 patients 5 patients 7 hospitalized 6 initially 7 hospitalized 7 hospitalized 8 in 7 hospitalized 14 to 8 in 10 institution 9 our 10 institution 10 institution 11 from 11 from 12 april 12 april 13 2004 14 to 15 december 15 december 16 2009 risk scores were calculated for each patient using 4 risk score models , including the seattle heart failure model ( shfm ) , acute decompensated heart failure national registry regression model , the [american] heart association get with the guidelines - heart failure score , and the association of health aging and body composition heart failure score . 0 ###LEFT-WALL### 1 risk 0 ###LEFT-WALL### 4 calculated 0 ###LEFT-WALL### 23 , 1 risk 2 scores 1 risk 3 were 1 risk 4 calculated 2 scores 3 were 4 calculated 5 for 4 calculated 8 using 5 for 7 patient 6 each 7 patient 8 using 12 models 8 using 14 including 9 4 12 models 10 risk 11 score 11 score 12 models 13 , 14 including 14 including 21 shfm 14 including 22 ) 15 the 21 shfm 16 seattle 17 heart 17 heart 18 failure 18 failure 19 model 19 model 21 shfm 20 ( 21 shfm 21 shfm 22 ) 23 , 31 model 23 , 32 , 24 acute 25 decompensated 25 decompensated 26 heart 26 heart 27 failure 27 failure 28 national 28 national 29 registry 29 registry 31 model 30 regression 31 model 32 , 40 guidelines 32 , 41 - 33 the 40 guidelines 35 heart 36 association 36 association 37 get 37 get 38 with 38 with 39 the 39 the 40 guidelines 41 - 44 score 41 - 46 and 41 - 58 . 42 heart 43 failure 43 failure 44 score 45 , 46 and 46 and 52 and 46 and 57 score 47 the 51 aging 48 association 49 of 48 association 51 aging 49 of 50 health 51 aging 52 and 52 and 56 failure 52 and 57 score 53 body 54 composition 54 composition 55 heart 55 heart 56 failure the predictive ability for the composite end point , including total death , heart transplantation , and left ventricle assist device implantation , [was] assessed by calculating the area under the receiver operating characteristic curve for each model . 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 23 , 0 ###LEFT-WALL### 39 . 1 the 3 ability 2 predictive 3 ability 3 ability 4 for 3 ability 9 , 4 for 8 point 5 the 8 point 6 composite 7 end 7 end 8 point 9 , 12 death 9 , 13 , 10 including 12 death 11 total 12 death 13 , 15 transplantation 13 , 17 and 14 heart 15 transplantation 16 , 17 and 17 and 19 ventricle 17 and 23 , 18 left 19 ventricle 20 assist 22 implantation 20 assist 23 , 21 device 22 implantation 23 , 25 assessed 23 , 26 by 23 , 30 under 26 by 27 calculating 27 calculating 29 area 28 the 29 area 30 under 35 curve 31 the 35 curve 32 receiver 33 operating 33 operating 35 curve 34 characteristic 35 curve 35 curve 36 for 36 for 38 model 37 each 38 model during the [follow] [-] up period after admission ( median 924.5 days ) , the combined end point occurred in 295 patients ( 11.8 % ) , including 27 in - hospital deaths ( 1.1 % ) . 0 ###LEFT-WALL### 18 point 0 ###LEFT-WALL### 19 occurred 0 ###LEFT-WALL### 38 . 1 during 6 period 1 during 14 , 1 during 18 point 2 the 6 period 5 up 6 period 6 period 7 after 6 period 12 days 7 after 8 admission 9 ( 12 days 10 median 12 days 11 924.5 12 days 12 days 13 ) 15 the 18 point 16 combined 17 end 17 end 18 point 18 point 19 occurred 19 occurred 20 in 20 in 22 patients 21 295 22 patients 22 patients 25 % 22 patients 28 including 22 patients 33 deaths 23 ( 25 % 24 11.8 25 % 25 % 26 ) 27 , 28 including 28 including 30 in 28 including 31 - 29 27 30 in 31 - 33 deaths 32 hospital 33 deaths 33 deaths 36 % 33 deaths 37 ) 34 ( 36 % 35 1.1 36 % 36 % 37 ) compared with the other 3 risk score models , the shfm risk score demonstrated a greater area under the curve for the combined end point at the overall , in - [hospital] [,] 30 - day , [and] 1 - , 2 - , and 3 - [year] follow - up point ( [0.741] to 0.890 ) . 0 ###LEFT-WALL### 13 score 0 ###LEFT-WALL### 41 , 1 compared 2 with 1 compared 9 , 1 compared 13 score 2 with 8 models 3 the 4 other 4 other 5 3 5 3 8 models 6 risk 8 models 7 score 8 models 10 the 13 score 11 shfm 13 score 12 risk 13 score 13 score 14 demonstrated 14 demonstrated 17 area 15 a 17 area 16 greater 17 area 17 area 18 under 17 area 21 for 17 area 26 at 18 under 20 curve 19 the 20 curve 21 for 25 point 22 the 25 point 23 combined 24 end 24 end 25 point 26 at 28 overall 27 the 28 overall 28 overall 30 in 28 overall 36 day 29 , 30 in 30 in 34 30 30 in 35 - 31 - 34 30 35 - 36 day 36 day 39 1 36 day 41 , 37 , 39 1 39 1 40 - 41 , 42 2 41 , 43 - 41 , 50 - 42 2 43 - 43 - 45 and 44 , 45 and 45 and 46 3 45 and 47 - 46 3 47 - 47 - 49 follow 50 - 52 point 50 - 58 . 51 up 52 point 52 point 55 to 53 ( 55 to 55 to 56 0.890 55 to 57 ) the survival rate predicted by shfm demonstrated an excellent correlation with the actual survival rate [(] r ( 2 [ )(= 0.990 ) . 0 ###LEFT-WALL### 3 rate 0 ###LEFT-WALL### 7 demonstrated 0 ###LEFT-WALL### 24 . 1 the 3 rate 2 survival 3 rate 3 rate 4 predicted 3 rate 7 demonstrated 4 predicted 5 by 5 by 6 shfm 7 demonstrated 10 correlation 8 an 9 excellent 8 an 10 correlation 9 excellent 10 correlation 10 correlation 11 with 10 correlation 21 )(= 11 with 15 rate 12 the 15 rate 13 actual 14 survival 14 survival 15 rate 17 r 21 )(= 18 ( 21 )(= 19 2 21 )(= 21 )(= 22 0.990 21 )(= 23 ) in conclusion , these results suggest that the shfm risk score is the most suitable for the discrimination and calibration of mortality risk stratification in patients with cardiovascular disease . 0 ###LEFT-WALL### 2 conclusion 0 ###LEFT-WALL### 3 , 0 ###LEFT-WALL### 30 . 1 in 2 conclusion 3 , 12 is 4 these 5 results 5 results 6 suggest 6 suggest 7 that 7 that 11 score 7 that 12 is 8 the 11 score 9 shfm 11 score 10 risk 11 score 12 is 14 most 12 is 15 suitable 13 the 14 most 15 suitable 16 for 15 suitable 25 in 15 suitable 27 with 16 for 19 and 17 the 18 discrimination 18 discrimination 19 and 19 and 20 calibration 19 and 21 of 21 of 24 stratification 22 mortality 24 stratification 23 risk 24 stratification 25 in 26 patients 27 with 29 disease 28 cardiovascular 29 disease background : african americans have historically had high high - density lipoprotein cholesterol ( hdl - c ) compared with other races and ethnicities . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 25 . 2 : 4 americans 2 : 7 had 3 african 4 americans 4 americans 5 have 5 have 7 had 6 historically 7 had 7 had 13 cholesterol 7 had 16 - 7 had 19 compared 8 high 11 density 9 high 10 - 9 high 11 density 11 density 13 cholesterol 12 lipoprotein 13 cholesterol 14 ( 16 - 15 hdl 16 - 16 - 17 c 16 - 18 ) 19 compared 20 with 20 with 23 and 21 other 22 races 22 races 23 and 23 and 24 ethnicities objective [:] we sought to characterize whether there is a cross - sectional association [between] age and hdl - [c] in a contemporary community - based study of african americans . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 26 based 0 ###LEFT-WALL### 31 . 1 objective 3 we 1 objective 6 characterize 1 objective 17 and 1 objective 26 based 3 we 4 sought 4 sought 5 to 4 sought 6 characterize 5 to 6 characterize 6 characterize 7 whether 7 whether 8 there 7 whether 9 is 8 there 9 is 9 is 11 cross 10 a 11 cross 12 - 17 and 13 sectional 14 association 14 association 16 age 16 age 17 and 17 and 18 hdl 17 and 19 - 17 and 21 in 17 and 25 - 21 in 24 community 22 a 24 community 23 contemporary 24 community 26 based 27 study 27 study 28 of 28 of 30 americans 29 african 30 americans methods : cross - sectional data were modeled by logistic regression for predictors of hdl - [c] among african americans , ages 35 - 74 , participating in the baseline examination of a community - based study of cardiovascular disease in jackson , mississippi , during 2000 - 2004 . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 4 - 0 ###LEFT-WALL### 36 based 0 ###LEFT-WALL### 50 . 1 methods 2 : 2 : 3 cross 4 - 6 data 4 - 8 modeled 4 - 21 , 4 - 24 - 5 sectional 6 data 6 data 7 were 7 were 8 modeled 8 modeled 9 by 8 modeled 12 for 8 modeled 18 among 9 by 11 regression 10 logistic 11 regression 12 for 13 predictors 13 predictors 14 of 14 of 15 hdl 16 - 18 among 18 among 20 americans 18 among 21 , 19 african 20 americans 21 , 22 ages 23 35 24 - 24 - 25 74 25 74 27 participating 25 74 36 based 26 , 27 participating 27 participating 28 in 27 participating 35 - 28 in 31 examination 29 the 31 examination 30 baseline 31 examination 31 examination 32 of 32 of 34 community 33 a 34 community 36 based 37 study 36 based 41 in 36 based 46 during 37 study 38 of 38 of 40 disease 39 cardiovascular 40 disease 41 in 42 jackson 42 jackson 44 mississippi 43 , 44 mississippi 44 mississippi 45 , 46 during 48 - 47 2000 48 - 48 - 49 2004 after excluding persons taking [lipid] - lowering medications , hormone replacement therapy , oral contraceptives , or thyroid replacement , the analytical data set comprised 2420 persons ( 1370 women , 1050 men ) . 0 ###LEFT-WALL### 24 set 0 ###LEFT-WALL### 25 comprised 0 ###LEFT-WALL### 35 . 1 after 2 excluding 1 after 20 , 1 after 24 set 2 excluding 17 or 3 persons 4 taking 3 persons 13 , 4 taking 7 lowering 4 taking 12 therapy 6 - 7 lowering 7 lowering 8 medications 7 lowering 9 , 10 hormone 12 therapy 11 replacement 12 therapy 13 , 15 contraceptives 13 , 17 or 14 oral 15 contraceptives 16 , 17 or 17 or 19 replacement 18 thyroid 19 replacement 21 the 24 set 22 analytical 23 data 23 data 24 set 24 set 25 comprised 25 comprised 27 persons 26 2420 27 persons 27 persons 30 women 28 ( 30 women 29 1370 30 women 30 women 33 men 30 women 34 ) 31 , 33 men 32 1050 33 men 33 men 34 ) results : hdl [-] c had a significant positive association with age after controlling for serum triglycerides , sex , waist circumference , percent dietary calories from carbohydrates , alcohol use , and leisure physical activity . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 3 hdl 2 : 6 had 2 : 37 . 3 hdl 5 c 3 hdl 6 had 6 had 10 association 6 had 11 with 6 had 13 after 7 a 8 significant 7 a 10 association 8 significant 10 association 9 positive 10 association 11 with 12 age 13 after 14 controlling 14 controlling 15 for 14 controlling 33 and 15 for 16 serum 17 triglycerides 18 , 18 , 19 sex 18 , 20 , 20 , 22 circumference 20 , 23 , 21 waist 22 circumference 23 , 26 calories 23 , 33 and 24 percent 26 calories 25 dietary 26 calories 26 calories 27 from 27 from 28 carbohydrates 28 carbohydrates 31 use 29 , 31 use 30 alcohol 31 use 31 use 32 , 33 and 36 activity 34 leisure 36 activity 35 physical 36 activity sex was a significant effect modifier of this relationship , whereby the increase in hdl [-] c with age was steeper for women than for men . 0 ###LEFT-WALL### 1 sex 0 ###LEFT-WALL### 2 was 1 sex 2 was 2 was 6 modifier 2 was 11 whereby 3 a 4 significant 3 a 6 modifier 4 significant 5 effect 5 effect 6 modifier 6 modifier 7 of 7 of 9 relationship 8 this 9 relationship 10 , 11 whereby 11 whereby 13 increase 11 whereby 20 was 11 whereby 27 . 12 the 13 increase 13 increase 14 in 13 increase 20 was 14 in 15 hdl 15 hdl 17 c 15 hdl 18 with 18 with 19 age 20 was 21 steeper 21 steeper 22 for 21 steeper 24 than 22 for 23 women 24 than 25 for 25 for 26 men conclusions : cross - sectional analysis found a positive association of hdl [-] c with age while [controlling] for triglycerides . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 4 - 0 ###LEFT-WALL### 21 . 1 conclusions 2 : 2 : 3 cross 4 - 6 analysis 4 - 7 found 5 sectional 6 analysis 6 analysis 7 found 7 found 10 association 7 found 15 with 7 found 17 while 8 a 9 positive 8 a 10 association 9 positive 10 association 10 association 11 of 11 of 12 hdl 12 hdl 14 c 15 with 16 age 17 while 19 for 19 for 20 triglycerides careful [evaluation] of longitudinal data will be needed to confirm whether this is a true effect of aging , or a cohort or survivor effect . 0 ###LEFT-WALL### 1 careful 0 ###LEFT-WALL### 8 needed 0 ###LEFT-WALL### 10 confirm 1 careful 3 of 1 careful 6 will 1 careful 7 be 1 careful 8 needed 3 of 5 data 4 longitudinal 5 data 6 will 7 be 8 needed 9 to 8 needed 10 confirm 9 to 10 confirm 10 confirm 11 whether 10 confirm 26 . 11 whether 12 this 11 whether 13 is 12 this 13 is 13 is 23 or 14 a 15 true 14 a 16 effect 15 true 16 effect 16 effect 17 of 16 effect 20 or 17 of 18 aging 19 , 20 or 20 or 22 cohort 20 or 23 or 21 a 22 cohort 23 or 25 effect 24 survivor 25 effect objective : in emergency care of patients with severe blunt head injury , uncontrollable high intracranial pressure is one of major causes of morbidity and mortality . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 13 , 0 ###LEFT-WALL### 27 . 1 objective 2 : 2 : 3 in 2 : 8 with 3 in 5 care 4 emergency 5 care 5 care 6 of 6 of 7 patients 8 with 12 injury 9 severe 11 head 10 blunt 11 head 11 head 12 injury 13 , 17 pressure 13 , 18 is 14 uncontrollable 17 pressure 15 high 17 pressure 16 intracranial 17 pressure 17 pressure 18 is 18 is 25 and 19 one 20 of 19 one 25 and 20 of 22 causes 21 major 22 causes 22 causes 23 of 23 of 24 morbidity 25 and 26 mortality the purpose of this study was to evaluate the efficacy of aggressive surgical treatment in managing uncontrollable elevated intracranial pressure coupled with early skull reconstruction . 0 ###LEFT-WALL### 2 purpose 0 ###LEFT-WALL### 21 coupled 0 ###LEFT-WALL### 26 . 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 21 coupled 7 to 8 evaluate 8 evaluate 10 efficacy 8 evaluate 15 in 9 the 10 efficacy 10 efficacy 11 of 11 of 14 treatment 12 aggressive 14 treatment 13 surgical 14 treatment 15 in 16 managing 16 managing 20 pressure 17 uncontrollable 20 pressure 18 elevated 20 pressure 19 intracranial 20 pressure 21 coupled 22 with 22 with 25 reconstruction 23 early 24 skull 24 skull 25 reconstruction methods : this was a prospective study on a series of 147 consecutive patients , managed according to the same protocol by five different neurosurgical units , for severe head injuries ( glasgow coma scale score ≤8/15 and high intracranial pressure >25 [mm] [hg] ) during a five [-] year period . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 3 this 2 : 4 was 2 : 52 . 3 this 4 was 4 was 7 study 4 was 8 on 4 was 28 for 4 was 46 during 5 a 7 study 6 prospective 7 study 8 on 10 series 9 a 10 series 10 series 11 of 11 of 14 patients 12 147 14 patients 13 consecutive 14 patients 14 patients 16 managed 15 , 16 managed 16 managed 18 to 16 managed 22 by 16 managed 27 , 17 according 18 to 18 to 21 protocol 19 the 20 same 19 the 21 protocol 22 by 26 units 23 five 26 units 24 different 26 units 25 neurosurgical 26 units 27 , 28 for 28 for 31 injuries 28 for 45 ) 29 severe 31 injuries 30 head 31 injuries 31 injuries 33 glasgow 32 ( 33 glasgow 33 glasgow 38 and 33 glasgow 42 >25 33 glasgow 45 ) 34 coma 37 ≤8/15 35 scale 36 score 36 score 37 ≤8/15 37 ≤8/15 38 and 38 and 41 pressure 38 and 42 >25 39 high 41 pressure 40 intracranial 41 pressure 46 during 51 period 47 a 51 period 48 five 50 year 50 year 51 period all patients received a wide decompressive craniectomy and duroplasty in the acute phase , and a cranioplasty was also performed within 12 weeks ( median 6 weeks , range 4 - 12 weeks ) . 0 ###LEFT-WALL### 2 patients 0 ###LEFT-WALL### 3 received 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 35 . 1 all 2 patients 2 patients 3 received 3 received 7 craniectomy 4 a 5 wide 4 a 7 craniectomy 5 wide 7 craniectomy 6 decompressive 7 craniectomy 8 and 9 duroplasty 8 and 20 performed 9 duroplasty 10 in 9 duroplasty 18 was 10 in 15 and 11 the 13 phase 12 acute 13 phase 13 phase 15 and 14 , 15 and 15 and 17 cranioplasty 16 a 17 cranioplasty 18 was 20 performed 19 also 20 performed 20 performed 21 within 21 within 23 weeks 22 12 23 weeks 23 weeks 27 weeks 23 weeks 33 weeks 24 ( 27 weeks 25 median 27 weeks 26 6 27 weeks 27 weeks 29 range 27 weeks 31 - 28 , 29 range 29 range 30 4 29 range 31 - 31 - 33 weeks 32 12 33 weeks 33 weeks 34 ) results : the emergency decompressive surgery was performed within 28 hours ( median 16 hours , range 6 - 28 hours ) after sustaining the head injury . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 28 . 2 : 6 surgery 2 : 8 performed 3 the 6 surgery 4 emergency 6 surgery 5 decompressive 6 surgery 6 surgery 7 was 7 was 8 performed 8 performed 9 within 8 performed 23 after 9 within 11 hours 10 28 11 hours 11 hours 15 hours 11 hours 21 hours 12 ( 15 hours 13 median 15 hours 14 16 15 hours 15 hours 17 range 15 hours 19 - 16 , 17 range 17 range 18 6 17 range 19 - 19 - 21 hours 20 28 21 hours 21 hours 22 ) 23 after 24 sustaining 24 sustaining 27 injury 25 the 27 injury 26 head 27 injury the median preoperative glasgow coma scale score was 6/15 ( range 3 - 8/15 ) . 0 ###LEFT-WALL### 7 score 0 ###LEFT-WALL### 8 was 0 ###LEFT-WALL### 16 . 1 the 7 score 2 median 5 coma 3 preoperative 5 coma 4 glasgow 5 coma 5 coma 7 score 6 scale 7 score 7 score 8 was 8 was 9 6/15 9 6/15 11 range 10 ( 11 range 11 range 13 - 11 range 15 ) 12 3 13 - 13 - 14 8/15 at a mean follow - up of 26 months ( range 14 - 74 months ) 14 patients were lost to long [-] term follow - up , leaving only 133 patients available for the study . 0 ###LEFT-WALL### 4 follow 0 ###LEFT-WALL### 5 - 1 at 3 mean 1 at 4 follow 2 a 3 mean 5 - 17 14 5 - 25 follow 6 up 17 14 7 of 9 months 7 of 17 14 8 26 9 months 9 months 11 range 10 ( 11 range 11 range 12 14 11 range 15 months 11 range 16 ) 13 - 15 months 14 74 15 months 15 months 16 ) 17 14 18 patients 17 14 24 term 17 14 25 follow 18 patients 19 were 19 were 20 lost 20 lost 21 to 21 to 24 term 22 long 24 term 25 follow 27 up 25 follow 29 leaving 26 - 27 up 27 up 28 , 28 , 29 leaving 29 leaving 32 patients 29 leaving 37 . 30 only 31 133 31 133 32 patients 32 patients 33 available 33 available 34 for 34 for 36 study 35 the 36 study the outcome was favorable in 89 ( 67 % , glasgow outcome score 4 or 5 ) , it was not favorable in 25 ( 19 % , glasgow outcome score 2 and 3 ) , and 19 patients ( 14 % ) died . 0 ###LEFT-WALL### 2 outcome 0 ###LEFT-WALL### 3 was 0 ###LEFT-WALL### 18 , 0 ###LEFT-WALL### 45 . 1 the 2 outcome 2 outcome 3 was 3 was 4 favorable 4 favorable 5 in 5 in 6 89 6 89 9 % 6 89 13 score 7 ( 9 % 8 67 9 % 9 % 10 , 10 , 13 score 11 glasgow 13 score 12 outcome 13 score 13 score 15 or 13 score 17 ) 14 4 15 or 15 or 16 5 18 , 19 it 18 , 20 was 18 , 37 and 19 it 20 was 20 was 21 not 20 was 22 favorable 22 favorable 23 in 23 in 24 25 24 25 27 % 24 25 31 score 25 ( 27 % 26 19 27 % 27 % 28 , 28 , 31 score 29 glasgow 31 score 30 outcome 31 score 31 score 33 and 31 score 35 ) 32 2 33 and 33 and 34 3 36 , 37 and 37 and 39 patients 37 and 44 died 38 19 39 patients 39 patients 42 % 39 patients 44 died 40 ( 42 % 41 14 42 % 42 % 43 ) a younger age ( < 50 years [ )(and earlier operation ( within 9 hours from trauma ) had a significant effect on positive outcomes ( p < 0.0001 and p < 0.03 , respectively ) . 0 ###LEFT-WALL### 3 age 0 ###LEFT-WALL### 19 had 0 ###LEFT-WALL### 30 and 0 ###LEFT-WALL### 37 . 1 a 3 age 2 younger 3 age 3 age 9 )(and 3 age 19 had 4 ( 9 )(and 5 < 6 50 6 50 7 years 7 years 9 )(and 9 )(and 11 operation 9 )(and 13 within 9 )(and 18 ) 10 earlier 11 operation 12 ( 13 within 13 within 15 hours 13 within 18 ) 14 9 15 hours 15 hours 16 from 16 from 17 trauma 19 had 22 effect 19 had 23 on 20 a 21 significant 20 a 22 effect 21 significant 22 effect 23 on 25 outcomes 24 positive 25 outcomes 25 outcomes 28 < 26 ( 28 < 27 p 28 < 28 < 29 0.0001 30 and 31 p 30 and 32 < 31 p 32 < 32 < 33 0.03 32 < 35 respectively 34 , 35 respectively 35 respectively 36 ) conclusions : a prompt aggressive surgery , including a wide decompressive craniectomy coupled with early cranioplasty , could be an effective treatment method to improve the outcome after a severe closed head injury reducing , perhaps , many of the complications related to decompressive craniectomy . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 19 be 0 ###LEFT-WALL### 42 related 0 ###LEFT-WALL### 46 . 1 conclusions 2 : 2 : 4 prompt 3 a 4 prompt 4 prompt 6 surgery 4 prompt 19 be 5 aggressive 6 surgery 6 surgery 8 including 6 surgery 18 could 7 , 8 including 8 including 12 craniectomy 8 including 14 with 8 including 17 , 9 a 12 craniectomy 10 wide 12 craniectomy 11 decompressive 12 craniectomy 12 craniectomy 13 coupled 14 with 16 cranioplasty 15 early 16 cranioplasty 18 could 19 be 19 be 23 method 20 an 21 effective 20 an 23 method 21 effective 22 treatment 22 treatment 23 method 23 method 24 to 23 method 34 reducing 24 to 25 improve 25 improve 27 outcome 25 improve 28 after 26 the 27 outcome 28 after 33 injury 29 a 33 injury 30 severe 32 head 31 closed 32 head 32 head 33 injury 33 injury 34 reducing 34 reducing 36 perhaps 35 , 36 perhaps 36 perhaps 37 , 38 many 39 of 38 many 41 complications 39 of 41 complications 40 the 41 complications 41 complications 42 related 42 related 43 to 43 to 45 craniectomy 44 decompressive 45 craniectomy the increased interest in chemical [cross] - linking for probing protein structure and interaction has led to a large increase in literature describing new [cross] - linkers and search programs . 0 ###LEFT-WALL### 3 interest 0 ###LEFT-WALL### 16 led 0 ###LEFT-WALL### 31 . 1 the 3 interest 2 increased 3 interest 3 interest 4 in 3 interest 9 for 3 interest 15 has 4 in 8 linking 5 chemical 7 - 5 chemical 8 linking 9 for 10 probing 10 probing 13 and 11 protein 12 structure 12 structure 13 and 13 and 14 interaction 15 has 16 led 16 led 17 to 16 led 21 in 17 to 20 increase 18 a 20 increase 19 large 20 increase 21 in 28 and 22 literature 23 describing 22 literature 28 and 23 describing 27 linkers 24 new 26 - 24 new 27 linkers 28 and 30 programs 29 search 30 programs however , this has not led to a corresponding increase in the analysis of large and complex proteins . 0 ###LEFT-WALL### 3 this 0 ###LEFT-WALL### 6 led 0 ###LEFT-WALL### 19 . 1 however 2 , 1 however 3 this 3 this 4 has 4 has 5 not 4 has 6 led 6 led 7 to 6 led 11 in 7 to 10 increase 8 a 9 corresponding 8 a 10 increase 9 corresponding 10 increase 11 in 13 analysis 12 the 13 analysis 13 analysis 14 of 14 of 18 proteins 15 large 16 and 16 and 17 complex 16 and 18 proteins a major obstacle is that [the] new cross - linkers are either not readily [available] [and/or] have a low reactivity . 0 ###LEFT-WALL### 3 obstacle 0 ###LEFT-WALL### 4 is 0 ###LEFT-WALL### 9 - 1 a 3 obstacle 2 major 3 obstacle 3 obstacle 4 is 4 is 8 cross 5 that 8 cross 7 new 8 cross 9 - 10 linkers 9 - 17 have 9 - 21 . 10 linkers 11 are 11 are 13 not 11 are 17 have 12 either 13 not 14 readily 17 have 17 have 20 reactivity 18 a 19 low 18 a 20 reactivity 19 low 20 reactivity in combination [with] aging search programs that are slow and have low sensitivity , or new search programs that are described but not released , these efforts do little to advance the field of cross - linking . 0 ###LEFT-WALL### 15 or 0 ###LEFT-WALL### 35 cross 0 ###LEFT-WALL### 36 - 0 ###LEFT-WALL### 38 . 1 in 6 programs 1 in 15 or 2 combination 5 search 4 aging 5 search 5 search 6 programs 6 programs 7 that 6 programs 8 are 7 that 8 are 8 are 10 and 9 slow 10 and 10 and 11 have 12 low 15 or 13 sensitivity 15 or 14 , 15 or 15 or 17 search 15 or 18 programs 15 or 28 do 15 or 29 little 15 or 35 cross 16 new 17 search 18 programs 19 that 18 programs 20 are 18 programs 28 do 19 that 20 are 20 are 21 described 21 described 22 but 22 but 23 not 22 but 27 efforts 23 not 24 released 24 released 25 , 26 these 27 efforts 29 little 30 to 29 little 34 of 30 to 31 advance 31 advance 33 field 32 the 33 field 33 field 34 of 36 - 37 linking here we present a method pipeline for chemical [cross] - linking , using two standard cross - linkers , bs3 and bs2g , combined with our freely available crosswork search program . 0 ###LEFT-WALL### 2 we 0 ###LEFT-WALL### 3 present 0 ###LEFT-WALL### 12 , 1 here 2 we 2 we 3 present 3 present 6 pipeline 4 a 5 method 4 a 6 pipeline 5 method 6 pipeline 6 pipeline 7 for 7 for 11 linking 8 chemical 10 - 8 chemical 11 linking 12 , 16 cross 12 , 17 - 13 using 16 cross 14 two 15 standard 15 standard 16 cross 17 - 21 and 17 - 24 combined 17 - 32 . 18 linkers 19 , 19 , 20 bs3 19 , 21 and 21 and 22 bs2g 21 and 23 , 21 and 24 combined 24 combined 25 with 25 with 31 program 26 our 31 program 27 freely 28 available 28 available 30 search 29 crosswork 30 search 30 search 31 program by this approach we generate cross - link data sufficient to derive structural information for large and complex proteins . 0 ###LEFT-WALL### 6 cross 0 ###LEFT-WALL### 7 - 1 by 3 approach 1 by 6 cross 2 this 3 approach 3 approach 4 we 3 approach 5 generate 4 we 5 generate 7 - 8 link 7 - 20 . 8 link 9 data 9 data 10 sufficient 10 sufficient 11 to 10 sufficient 15 for 11 to 12 derive 12 derive 14 information 13 structural 14 information 15 for 19 proteins 16 large 17 and 17 and 18 complex 17 and 19 proteins crosswork searches batches of tandem mass - spectrometric data , and [identifies] cross - linked and [non] [-] cross - linked peptides using a standard pc . 0 ###LEFT-WALL### 2 searches 0 ###LEFT-WALL### 21 linked 0 ###LEFT-WALL### 27 . 1 crosswork 2 searches 2 searches 3 batches 2 searches 6 mass 2 searches 16 and 2 searches 21 linked 3 batches 4 of 3 batches 6 mass 4 of 5 tandem 7 - 16 and 8 spectrometric 9 data 9 data 11 and 10 , 11 and 11 and 13 cross 11 and 14 - 11 and 15 linked 11 and 16 and 16 and 19 cross 16 and 20 - 21 linked 22 peptides 22 peptides 23 using 23 using 26 pc 24 a 25 standard 24 a 26 pc 25 standard 26 pc we tested crosswork by searching [mass] - spectrometric datasets of cross - linked complement factor c3 [against] [small] ( 1 protein [ )(and large ( 1000 proteins ) search spaces , [and] show that [the] resulting distance constraints agree with the established structures . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 tested 1 we 2 tested 2 tested 3 crosswork 2 tested 12 - 3 crosswork 4 by 4 by 5 searching 7 - 12 - 8 spectrometric 9 datasets 9 datasets 10 of 9 datasets 12 - 10 of 11 cross 12 - 16 c3 13 linked 15 factor 14 complement 15 factor 15 factor 16 c3 16 c3 23 )(and 19 ( 23 )(and 20 1 21 protein 21 protein 23 )(and 23 )(and 30 spaces 23 )(and 31 , 24 large 27 proteins 24 large 30 spaces 25 ( 27 proteins 26 1000 27 proteins 27 proteins 28 ) 29 search 30 spaces 31 , 39 agree 33 show 38 constraints 34 that 36 resulting 36 resulting 38 constraints 37 distance 38 constraints 38 constraints 39 agree 39 agree 40 with 39 agree 44 . 40 with 43 structures 41 the 43 structures 42 established 43 structures we further investigated the structure of the multi - domain erp72 , and combined the individual domains of erp72 into a single structure . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 24 . 1 we 13 and 2 further 3 investigated 3 investigated 5 structure 3 investigated 13 and 4 the 5 structure 5 structure 6 of 6 of 11 erp72 7 the 10 domain 8 multi 9 - 8 multi 10 domain 10 domain 11 erp72 12 , 13 and 13 and 14 combined 14 combined 17 domains 14 combined 20 into 15 the 17 domains 16 individual 17 domains 17 domains 18 of 18 of 19 erp72 20 into 23 structure 21 a 22 single 21 a 23 structure 22 single 23 structure given the central role of dna in life , and how ageing can be seen as the gradual and irreversible breakdown of living systems , the idea that damage to the dna is the crucial cause of ageing remains a powerful one . 0 ###LEFT-WALL### 14 be 0 ###LEFT-WALL### 25 , 0 ###LEFT-WALL### 43 . 1 given 12 ageing 2 the 4 role 3 central 4 role 4 role 5 of 4 role 7 in 4 role 10 and 5 of 6 dna 7 in 8 life 9 , 10 and 10 and 11 how 10 and 12 ageing 12 ageing 13 can 13 can 14 be 14 be 15 seen 15 seen 16 as 16 as 21 breakdown 17 the 21 breakdown 18 gradual 19 and 19 and 20 irreversible 19 and 21 breakdown 21 breakdown 22 of 22 of 24 systems 23 living 24 systems 25 , 27 idea 25 , 39 remains 26 the 27 idea 27 idea 28 that 27 idea 39 remains 28 that 29 damage 28 that 33 is 29 damage 30 to 29 damage 33 is 30 to 32 dna 31 the 32 dna 33 is 36 cause 34 the 36 cause 35 crucial 36 cause 36 cause 37 of 37 of 38 ageing 39 remains 42 one 40 a 41 powerful 40 a 42 one 41 powerful 42 one dna damage and mutations of different types clearly accumulate with age in mammalian tissues . 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 9 accumulate 0 ###LEFT-WALL### 15 . 1 dna 2 damage 2 damage 3 and 3 and 4 mutations 3 and 5 of 3 and 9 accumulate 5 of 7 types 6 different 7 types 8 clearly 9 accumulate 9 accumulate 10 with 9 accumulate 12 in 10 with 11 age 12 in 14 tissues 13 mammalian 14 tissues human progeroid syndromes resulting in what appears to be accelerated ageing have been linked to defects in dna repair or processing , suggesting that elevated levels of dna damage can accelerate physiological [decline] and the development of age - related diseases not limited to cancer . 0 ###LEFT-WALL### 22 , 0 ###LEFT-WALL### 40 related 0 ###LEFT-WALL### 46 . 1 human 2 progeroid 2 progeroid 3 syndromes 2 progeroid 13 been 2 progeroid 14 linked 3 syndromes 4 resulting 3 syndromes 5 in 3 syndromes 12 have 5 in 6 what 6 what 7 appears 7 appears 8 to 7 appears 9 be 8 to 9 be 9 be 11 ageing 10 accelerated 11 ageing 12 have 13 been 14 linked 15 to 14 linked 17 in 14 linked 22 , 15 to 16 defects 17 in 20 or 18 dna 19 repair 19 repair 20 or 20 or 21 processing 22 , 31 accelerate 23 suggesting 24 that 23 suggesting 25 elevated 23 suggesting 30 can 24 that 25 elevated 25 elevated 26 levels 26 levels 27 of 27 of 29 damage 28 dna 29 damage 30 can 31 accelerate 31 accelerate 34 and 32 physiological 34 and 34 and 36 development 34 and 37 of 35 the 36 development 37 of 38 age 39 - 40 related 40 related 41 diseases 40 related 44 to 41 diseases 42 not 42 not 43 limited 44 to 45 cancer higher dna damage may trigger cellular signalling pathways , such as apoptosis , that result in [a] faster depletion of stem cells , which in turn contributes to accelerated ageing . 0 ###LEFT-WALL### 3 damage 0 ###LEFT-WALL### 5 trigger 0 ###LEFT-WALL### 23 , 0 ###LEFT-WALL### 31 . 1 higher 3 damage 2 dna 3 damage 3 damage 4 may 4 may 5 trigger 5 trigger 8 pathways 6 cellular 8 pathways 7 signalling 8 pathways 8 pathways 11 as 9 , 11 as 10 such 11 as 11 as 12 apoptosis 11 as 23 , 12 apoptosis 14 that 12 apoptosis 15 result 13 , 14 that 14 that 15 result 15 result 16 in 16 in 19 depletion 18 faster 19 depletion 19 depletion 20 of 20 of 22 cells 21 stem 22 cells 23 , 24 which 23 , 27 contributes 24 which 27 contributes 25 in 26 turn 26 turn 27 contributes 27 contributes 28 to 28 to 30 ageing 29 accelerated 30 ageing genetic manipulations of dna repair pathways in mice further strengthen this view and also indicate that disruption of specific pathways , such as nucleotide excision repair and [non] [-] homologous end joining , is more strongly associated with premature ageing [phenotypes] . 0 ###LEFT-WALL### 2 manipulations 0 ###LEFT-WALL### 42 . 1 genetic 2 manipulations 2 manipulations 3 of 2 manipulations 6 pathways 2 manipulations 9 further 2 manipulations 13 and 3 of 4 dna 5 repair 6 pathways 6 pathways 7 in 6 pathways 9 further 7 in 8 mice 10 strengthen 12 view 10 strengthen 13 and 11 this 12 view 13 and 15 indicate 14 also 15 indicate 15 indicate 16 that 16 that 17 disruption 16 that 37 associated 17 disruption 18 of 17 disruption 23 as 17 disruption 34 is 18 of 20 pathways 19 specific 20 pathways 21 , 23 as 22 such 23 as 23 as 27 and 23 as 33 , 24 nucleotide 26 repair 25 excision 26 repair 26 repair 27 and 27 and 31 end 27 and 32 joining 30 homologous 31 end 34 is 36 strongly 34 is 37 associated 35 more 36 strongly 37 associated 38 with 38 with 40 ageing 39 premature 40 ageing delaying ageing in mice by decreasing levels of dna damage , however , has not been achieved yet , perhaps due to the complexity inherent to dna repair and dna damage response pathways . 0 ###LEFT-WALL### 29 and 0 ###LEFT-WALL### 31 damage 0 ###LEFT-WALL### 34 . 1 delaying 2 ageing 1 delaying 3 in 1 delaying 19 , 1 delaying 29 and 3 in 4 mice 4 mice 5 by 5 by 6 decreasing 6 decreasing 7 levels 7 levels 8 of 8 of 9 dna 9 dna 10 damage 9 dna 16 been 9 dna 17 achieved 10 damage 14 has 11 , 12 however 12 however 13 , 12 however 14 has 14 has 15 not 14 has 16 been 17 achieved 18 yet 20 perhaps 29 and 21 due 22 to 22 to 24 complexity 22 to 29 and 23 the 24 complexity 24 complexity 25 inherent 25 inherent 26 to 26 to 27 dna 28 repair 29 and 29 and 30 dna 29 and 31 damage 31 damage 33 pathways 32 response 33 pathways another open question is whether dna repair [optimization] is involved in the evolution of species longevity , and we suggest that the way cells from different organisms respond to dna damage may be crucial in species differences in ageing . 0 ###LEFT-WALL### 3 question 0 ###LEFT-WALL### 4 is 0 ###LEFT-WALL### 18 and 0 ###LEFT-WALL### 28 respond 0 ###LEFT-WALL### 40 . 1 another 3 question 2 open 3 question 3 question 4 is 4 is 5 whether 4 is 11 in 5 whether 7 repair 5 whether 9 is 6 dna 7 repair 7 repair 9 is 9 is 10 involved 11 in 13 evolution 12 the 13 evolution 13 evolution 14 of 14 of 16 longevity 15 species 16 longevity 17 , 18 and 18 and 19 we 18 and 20 suggest 19 we 20 suggest 20 suggest 21 that 21 that 24 cells 21 that 28 respond 22 the 24 cells 23 way 24 cells 24 cells 25 from 25 from 27 organisms 26 different 27 organisms 28 respond 29 to 28 respond 31 damage 28 respond 33 be 29 to 30 dna 31 damage 32 may 32 may 33 be 33 be 34 crucial 34 crucial 35 in 35 in 37 differences 36 species 37 differences 37 differences 38 in 38 in 39 ageing taken together , the data suggest a major role of dna damage in the modulation of longevity , possibly through effects on cell dysfunction and loss , although understanding how to modify dna damage repair and response systems to delay ageing remains a crucial challenge . 0 ###LEFT-WALL### 5 data 0 ###LEFT-WALL### 6 suggest 0 ###LEFT-WALL### 46 . 1 taken 2 together 1 taken 3 , 1 taken 5 data 4 the 5 data 5 data 6 suggest 6 suggest 9 role 6 suggest 13 in 6 suggest 20 through 6 suggest 28 although 7 a 9 role 8 major 9 role 9 role 10 of 10 of 12 damage 11 dna 12 damage 13 in 15 modulation 14 the 15 modulation 15 modulation 16 of 16 of 17 longevity 18 , 19 possibly 18 , 20 through 20 through 25 and 20 through 27 , 21 effects 22 on 21 effects 25 and 22 on 24 dysfunction 23 cell 24 dysfunction 25 and 26 loss 28 although 29 understanding 28 although 42 remains 29 understanding 30 how 29 understanding 42 remains 30 how 31 to 30 how 40 delay 31 to 32 modify 32 modify 36 and 32 modify 39 to 33 dna 35 repair 34 damage 35 repair 35 repair 36 and 36 and 38 systems 37 response 38 systems 39 to 40 delay 40 delay 41 ageing 42 remains 45 challenge 43 a 44 crucial 43 a 45 challenge 44 crucial 45 challenge markets are mechanisms of social exchange , intended to facilitate trading . 0 ###LEFT-WALL### 1 markets 0 ###LEFT-WALL### 2 are 1 markets 2 are 2 are 3 mechanisms 3 mechanisms 4 of 4 of 6 exchange 5 social 6 exchange 6 exchange 8 intended 7 , 8 intended 8 intended 9 to 8 intended 10 facilitate 8 intended 12 . 9 to 10 facilitate 10 facilitate 11 trading however , the question remains as to whether markets would help or hurt individuals with decision [-] makings deficits , [as] is frequently encountered in the case of cognitive aging . 0 ###LEFT-WALL### 4 question 0 ###LEFT-WALL### 20 , 0 ###LEFT-WALL### 31 . 1 however 2 , 1 however 4 question 3 the 4 question 4 question 20 , 5 remains 7 to 5 remains 15 with 5 remains 20 , 6 as 7 to 7 to 8 whether 8 whether 9 markets 8 whether 12 or 9 markets 12 or 10 would 11 help 10 would 12 or 12 or 13 hurt 12 or 14 individuals 15 with 18 makings 15 with 19 deficits 16 decision 18 makings 20 , 22 is 22 is 24 encountered 23 frequently 24 encountered 24 encountered 25 in 25 in 27 case 26 the 27 case 27 case 28 of 28 of 30 aging 29 cognitive 30 aging essential for predicting future gains and losses in monetary and social domains , the striatal nuclei in the brain undergo structural , neurochemical , and functional decline with age . 0 ###LEFT-WALL### 6 and 0 ###LEFT-WALL### 27 decline 0 ###LEFT-WALL### 30 . 1 essential 2 for 1 essential 6 and 2 for 3 predicting 3 predicting 5 gains 4 future 5 gains 6 and 7 losses 6 and 8 in 6 and 16 nuclei 6 and 20 undergo 6 and 27 decline 8 in 10 and 9 monetary 10 and 10 and 12 domains 10 and 13 , 11 social 12 domains 14 the 16 nuclei 15 striatal 16 nuclei 16 nuclei 17 in 16 nuclei 20 undergo 17 in 19 brain 18 the 19 brain 20 undergo 25 and 21 structural 22 , 22 , 23 neurochemical 22 , 25 and 24 , 25 and 25 and 26 functional 27 decline 28 with 28 with 29 age we correlated the efficacy of market mechanisms with dorsal striatal decline [in] [an] aging population , by using market based trading in the context of the 2008 u.s [.] presidential elections [(] primary cycle ) . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 correlated 0 ###LEFT-WALL### 36 . 1 we 2 correlated 2 correlated 4 efficacy 3 the 4 efficacy 4 efficacy 5 of 4 efficacy 8 with 4 efficacy 17 by 5 of 7 mechanisms 6 market 7 mechanisms 8 with 15 population 9 dorsal 11 decline 10 striatal 11 decline 11 decline 14 aging 14 aging 15 population 16 , 17 by 17 by 18 using 17 by 35 ) 18 using 21 trading 19 market 20 based 20 based 21 trading 21 trading 22 in 22 in 24 context 23 the 24 context 24 context 25 of 25 of 34 cycle 26 the 34 cycle 27 2008 28 u.s 28 u.s 30 presidential 30 presidential 34 cycle 31 elections 34 cycle 33 primary 34 cycle impaired [decision] - makers displayed higher prediction error ( [difference] between their prediction and actual outcome ) . 0 ###LEFT-WALL### 4 makers 0 ###LEFT-WALL### 5 displayed 0 ###LEFT-WALL### 18 . 1 impaired 3 - 1 impaired 4 makers 4 makers 5 displayed 5 displayed 8 error 6 higher 7 prediction 7 prediction 8 error 8 error 11 between 9 ( 11 between 11 between 14 and 11 between 17 ) 12 their 13 prediction 13 prediction 14 and 14 and 16 outcome 15 actual 16 outcome lower in vivo caudate volume was also associated with higher prediction error . 0 ###LEFT-WALL### 5 volume 0 ###LEFT-WALL### 8 associated 0 ###LEFT-WALL### 13 . 1 lower 5 volume 2 in 3 vivo 3 vivo 4 caudate 4 caudate 5 volume 5 volume 6 was 6 was 8 associated 7 also 8 associated 8 associated 9 with 9 with 12 error 10 higher 11 prediction 11 prediction 12 error importantly , market [-] based trading protected older adults with lower caudate volume to a greater extent from their own poorly calibrated predictions . 0 ###LEFT-WALL### 6 trading 0 ###LEFT-WALL### 7 protected 0 ###LEFT-WALL### 24 . 1 importantly 2 , 1 importantly 6 trading 3 market 5 based 5 based 6 trading 6 trading 7 protected 7 protected 9 adults 7 protected 14 to 7 protected 18 from 8 older 9 adults 9 adults 10 with 10 with 13 volume 11 lower 13 volume 12 caudate 13 volume 14 to 17 extent 15 a 17 extent 16 greater 17 extent 18 from 23 predictions 19 their 20 own 19 their 23 predictions 21 poorly 22 calibrated 22 calibrated 23 predictions counterintuitive to the traditional public perception of the market as a fickle , risky proposition where vulnerable traders are most surely to be burned , we suggest that market - based mechanisms protect individuals with brain - based [decision] - making vulnerabilities . 0 ###LEFT-WALL### 32 mechanisms 0 ###LEFT-WALL### 33 protect 0 ###LEFT-WALL### 43 . 1 counterintuitive 32 mechanisms 2 to 6 perception 2 to 30 - 2 to 32 mechanisms 3 the 6 perception 4 traditional 6 perception 5 public 6 perception 6 perception 7 of 6 perception 16 where 7 of 9 market 8 the 9 market 9 market 10 as 10 as 15 proposition 11 a 12 fickle 11 a 15 proposition 12 fickle 13 , 12 fickle 15 proposition 14 risky 15 proposition 16 where 18 traders 16 where 19 are 17 vulnerable 18 traders 18 traders 19 are 19 are 20 most 20 most 22 to 20 most 29 market 21 surely 22 to 22 to 25 , 23 be 24 burned 23 be 25 , 25 , 29 market 26 we 27 suggest 27 suggest 28 that 27 suggest 29 market 31 based 32 mechanisms 32 mechanisms 33 protect 33 protect 34 individuals 34 individuals 35 with 34 individuals 41 making 35 with 36 brain 36 brain 38 based 37 - 38 based 38 based 40 - 41 making 42 vulnerabilities humans display a large [inter] - individual variation in leukocyte telomere length ( ltl ) , which is influenced by heredity , sex , race/ethnicity , paternal age at conception and environmental exposures . 0 ###LEFT-WALL### 1 humans 0 ###LEFT-WALL### 2 display 0 ###LEFT-WALL### 16 , 0 ###LEFT-WALL### 34 . 1 humans 2 display 2 display 8 variation 2 display 9 in 3 a 4 large 3 a 8 variation 4 large 6 - 4 large 8 variation 7 individual 8 variation 9 in 12 length 10 leukocyte 12 length 11 telomere 12 length 12 length 14 ltl 13 ( 14 ltl 14 ltl 15 ) 16 , 17 which 16 , 19 influenced 16 , 26 , 17 which 18 is 18 is 19 influenced 19 influenced 20 by 20 by 21 heredity 21 heredity 23 sex 22 , 23 sex 23 sex 25 race/ethnicity 23 sex 26 , 24 , 25 race/ethnicity 25 race/ethnicity 26 , 26 , 31 and 27 paternal 28 age 28 age 29 at 28 age 31 and 29 at 30 conception 31 and 33 exposures 32 environmental 33 exposures ltl dynamics ( birth ltl and its age - dependent [attrition] thereafter ) mirror telomere dynamics in hematopoietic stem cells ( hscs ) . 0 ###LEFT-WALL### 2 dynamics 0 ###LEFT-WALL### 14 mirror 0 ###LEFT-WALL### 24 . 1 ltl 2 dynamics 2 dynamics 6 and 2 dynamics 10 dependent 2 dynamics 14 mirror 3 ( 6 and 4 birth 5 ltl 5 ltl 6 and 6 and 8 age 6 and 9 - 7 its 8 age 9 - 10 dependent 10 dependent 12 thereafter 10 dependent 13 ) 14 mirror 16 dynamics 14 mirror 17 in 15 telomere 16 dynamics 17 in 20 cells 18 hematopoietic 19 stem 19 stem 20 cells 20 cells 22 hscs 21 ( 22 hscs 22 hscs 23 ) ltl at birth is evidently a major determinant of ltl throughout the human lifespan , such that individuals endowed with short ( or long ) ltl at birth probably have short ( or long ) ltl later in life . 0 ###LEFT-WALL### 1 ltl 0 ###LEFT-WALL### 4 is 1 ltl 2 at 1 ltl 4 is 2 at 3 birth 4 is 5 evidently 4 is 8 determinant 4 is 11 throughout 4 is 17 that 6 a 8 determinant 7 major 8 determinant 8 determinant 9 of 9 of 10 ltl 11 throughout 14 lifespan 12 the 14 lifespan 13 human 14 lifespan 15 , 17 that 16 such 17 that 17 that 18 individuals 17 that 30 have 17 that 40 . 18 individuals 19 endowed 18 individuals 20 with 18 individuals 27 at 18 individuals 30 have 20 with 23 or 21 short 23 or 22 ( 23 or 23 or 26 ltl 24 long 25 ) 24 long 26 ltl 27 at 28 birth 29 probably 30 have 30 have 33 or 30 have 38 in 31 short 33 or 32 ( 33 or 33 or 36 ltl 33 or 37 later 34 long 35 ) 34 long 36 ltl 38 in 39 life therefore , the associations of short ltl with atherosclerosis and with diminished survival in the elderly may relate to short birth ltl , accelerated age - dependent ltl attrition , or both . 0 ###LEFT-WALL### 4 associations 0 ###LEFT-WALL### 18 relate 0 ###LEFT-WALL### 33 . 1 therefore 2 , 1 therefore 4 associations 3 the 4 associations 4 associations 5 of 4 associations 17 may 5 of 7 ltl 6 short 7 ltl 7 ltl 10 and 8 with 9 atherosclerosis 8 with 10 and 10 and 11 with 11 with 13 survival 12 diminished 13 survival 13 survival 14 in 14 in 16 elderly 15 the 16 elderly 17 may 18 relate 18 relate 19 to 19 to 31 or 20 short 21 birth 21 birth 29 attrition 22 ltl 25 age 22 ltl 29 attrition 23 , 25 age 24 accelerated 25 age 25 age 26 - 27 dependent 29 attrition 28 ltl 29 attrition 29 attrition 31 or 30 , 31 or 31 or 32 both the mechanisms underlying these associations are still not well understood , but they stem in part from genetic factors in control of telomere maintenance and the rate of hsc [replication] . 0 ###LEFT-WALL### 2 mechanisms 0 ###LEFT-WALL### 10 understood 0 ###LEFT-WALL### 12 but 0 ###LEFT-WALL### 31 . 1 the 2 mechanisms 2 mechanisms 3 underlying 2 mechanisms 6 are 3 underlying 5 associations 4 these 5 associations 6 are 8 not 6 are 9 well 6 are 10 understood 7 still 8 not 11 , 12 but 12 but 13 they 12 but 14 stem 13 they 14 stem 14 stem 16 part 15 in 16 part 16 part 17 from 17 from 19 factors 18 genetic 19 factors 19 factors 20 in 19 factors 22 of 19 factors 28 of 20 in 21 control 22 of 25 and 23 telomere 24 maintenance 24 maintenance 25 and 25 and 27 rate 26 the 27 rate 28 of 29 hsc objective : to estimate the degree of biological aging for healthy people by the biological age score equation and observe the differences of various aging biomarkers so as to provide targets for clinical anti - aging intervention . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 30 provide 0 ###LEFT-WALL### 38 . 2 : 3 to 2 : 19 and 3 to 19 and 4 estimate 12 people 4 estimate 13 by 4 estimate 19 and 5 the 6 degree 6 degree 7 of 6 degree 12 people 7 of 9 aging 8 biological 9 aging 9 aging 10 for 10 for 12 people 11 healthy 12 people 13 by 18 equation 14 the 18 equation 15 biological 16 age 16 age 18 equation 17 score 18 equation 19 and 20 observe 20 observe 22 differences 20 observe 29 to 21 the 22 differences 22 differences 23 of 23 of 26 biomarkers 24 various 26 biomarkers 25 aging 26 biomarkers 27 so 28 as 28 as 29 to 29 to 30 provide 30 provide 31 targets 31 targets 32 for 32 for 37 intervention 33 clinical 37 intervention 34 anti 35 - 34 anti 37 intervention 36 aging 37 intervention methods : a total of 2876 subjects aged 30 - 98 years old were recruited from 3 chinese cities in 2003 . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 10 - 0 ###LEFT-WALL### 22 . 1 methods 2 : 2 : 4 total 3 a 4 total 4 total 5 of 5 of 7 subjects 6 2876 7 subjects 7 subjects 8 aged 8 aged 9 30 10 - 11 98 10 - 15 recruited 11 98 13 old 11 98 14 were 12 years 13 old 14 were 15 recruited 15 recruited 16 from 16 from 19 cities 17 3 19 cities 18 chinese 19 cities 19 cities 20 in 20 in 21 2003 after screening , 852 healthy subjects were finally selected and assigned into 4 groups according to ages : young group ( < 45 yr [ )( middle - aged [group] ( 45 - 59 yr ) , young - elder group [(] 60 - 74 [yr] [ )(and elder group ( ≥ 75 [yr] [ )( 0 ###LEFT-WALL### 6 subjects 0 ###LEFT-WALL### 10 and 1 after 2 screening 1 after 3 , 1 after 6 subjects 4 852 6 subjects 5 healthy 6 subjects 6 subjects 7 were 7 were 10 and 8 finally 10 and 9 selected 10 and 10 and 11 assigned 11 assigned 12 into 11 assigned 14 groups 12 into 13 4 14 groups 15 according 14 groups 20 group 15 according 16 to 15 according 18 : 16 to 17 ages 18 : 20 group 19 young 20 group 20 group 28 - 21 ( 28 - 22 < 23 45 23 45 24 yr 24 yr 27 middle 27 middle 28 - 28 - 40 elder 29 aged 33 - 29 aged 37 , 29 aged 40 elder 31 ( 33 - 32 45 33 - 33 - 35 yr 33 - 36 ) 34 59 35 yr 38 young 39 - 38 young 40 elder 40 elder 48 )(and 40 elder 50 group 40 elder 52 ≥ 41 group 44 - 41 group 48 )(and 43 60 44 - 44 - 45 74 48 )(and 49 elder 48 )(and 50 group 51 ( 52 ≥ 52 ≥ 53 75 52 ≥ 56 )( they received a total of 108 physical , morphological , physiologic and biochemical examinations . 0 ###LEFT-WALL### 1 they 0 ###LEFT-WALL### 2 received 0 ###LEFT-WALL### 15 . 1 they 2 received 2 received 4 total 3 a 4 total 4 total 5 of 5 of 14 examinations 6 108 14 examinations 7 physical 8 , 7 physical 14 examinations 9 morphological 10 , 10 , 11 physiologic 10 , 12 and 12 and 13 biochemical 12 and 14 examinations the biological age score equation was employed to compute the individual biological age scores for all subjects . 0 ###LEFT-WALL### 5 equation 0 ###LEFT-WALL### 7 employed 0 ###LEFT-WALL### 18 . 1 the 5 equation 2 biological 3 age 3 age 4 score 4 score 5 equation 5 equation 6 was 6 was 7 employed 7 employed 8 to 7 employed 9 compute 8 to 9 compute 9 compute 14 scores 10 the 14 scores 11 individual 13 age 12 biological 13 age 13 age 14 scores 14 scores 15 for 15 for 17 subjects 16 all 17 subjects then the biological age score was taken as a dependent variable and the chronological age as an independent variable for linear regression . 0 ###LEFT-WALL### 5 score 0 ###LEFT-WALL### 7 taken 0 ###LEFT-WALL### 23 . 1 then 5 score 2 the 5 score 3 biological 4 age 4 age 5 score 5 score 6 was 6 was 7 taken 7 taken 8 as 7 taken 16 as 8 as 12 and 9 a 11 variable 10 dependent 11 variable 11 variable 12 and 12 and 15 age 13 the 15 age 14 chronological 15 age 16 as 19 variable 17 an 19 variable 18 independent 19 variable 19 variable 20 for 20 for 22 regression 21 linear 22 regression based on the confidence interval with ± 1 standard deviation of regression [line] , they were divided into 3 groups ( delayed aging , normal aging and early aging ) . 0 ###LEFT-WALL### 15 they 0 ###LEFT-WALL### 17 divided 0 ###LEFT-WALL### 31 . 1 based 2 on 1 based 6 with 1 based 14 , 1 based 15 they 2 on 5 interval 3 the 5 interval 4 confidence 5 interval 6 with 7 ± 6 with 10 deviation 7 ± 8 1 9 standard 10 deviation 10 deviation 11 of 11 of 12 regression 15 they 16 were 16 were 17 divided 17 divided 18 into 18 into 20 groups 19 3 20 groups 20 groups 27 and 21 ( 27 and 22 delayed 23 aging 23 aging 24 , 24 , 26 aging 24 , 27 and 25 normal 26 aging 27 and 28 early 27 and 29 aging 27 and 30 ) at the same time , the differences of 7 biomarkers were observed in different aging groups in 4 age groups . 0 ###LEFT-WALL### 7 differences 0 ###LEFT-WALL### 12 observed 0 ###LEFT-WALL### 21 . 1 at 4 time 1 at 5 , 1 at 7 differences 2 the 3 same 2 the 4 time 6 the 7 differences 7 differences 8 of 7 differences 11 were 8 of 10 biomarkers 9 7 10 biomarkers 11 were 12 observed 12 observed 13 in 12 observed 17 in 13 in 16 groups 14 different 16 groups 15 aging 16 groups 17 in 20 groups 18 4 20 groups 19 age 20 groups results : [(] 1 [ )(a comparison of biological age [score] : there were no significant differences in chronological age among 3 biological aging groups in same chronological age groups . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 12 : 0 ###LEFT-WALL### 31 . 1 results 2 : 2 : 7 comparison 4 1 6 )(a 6 )(a 7 comparison 7 comparison 8 of 8 of 10 age 9 biological 10 age 12 : 24 aging 12 : 30 groups 13 there 24 aging 14 were 17 differences 14 were 21 among 14 were 23 biological 14 were 24 aging 15 no 17 differences 16 significant 17 differences 17 differences 18 in 18 in 20 age 19 chronological 20 age 21 among 22 3 24 aging 25 groups 25 groups 26 in 26 in 27 same 27 same 29 age 27 same 30 groups 28 chronological 29 age 29 age 30 groups however , there were some significant differences in biological age score [(] young group [:] f = 91.8 , p < 0.01 [;] middle - aged [group] [:] f = 134.5 , p < 0.01 [;] young - elder [group] : f = 199.5 , p < 0.01 [;] elder group [:] f = 82.1 , p < 0.01 [ )( 0 ###LEFT-WALL### 7 differences 0 ###LEFT-WALL### 11 score 1 however 2 , 1 however 7 differences 3 there 7 differences 4 were 5 some 4 were 6 significant 4 were 7 differences 7 differences 8 in 7 differences 11 score 8 in 10 age 9 biological 10 age 11 score 13 young 11 score 14 group 14 group 16 f 14 group 18 91.8 14 group 24 middle 17 = 18 91.8 18 91.8 21 < 18 91.8 24 middle 19 , 21 < 20 p 21 < 21 < 22 0.01 24 middle 26 aged 25 - 26 aged 26 aged 30 = 26 aged 34 < 29 f 30 = 30 = 31 134.5 30 = 32 , 33 p 34 < 34 < 35 0.01 35 0.01 39 elder 35 0.01 41 : 35 0.01 47 < 37 young 38 - 37 young 39 elder 39 elder 41 : 41 : 43 = 42 f 43 = 43 = 44 199.5 43 = 45 , 46 p 47 < 47 < 50 elder 48 0.01 50 elder 50 elder 51 group 50 elder 54 = 51 group 53 f 51 group 54 = 54 = 58 < 55 82.1 58 < 56 , 58 < 57 p 58 < 58 < 59 0.01 58 < 61 )( [(] 2 [ )( - way analysis of variance ( aging groups and chronological age groups for biomarkers ) : there were significant differences of 7 biomarkers in different chronological age groups and different aging groups . 0 ###LEFT-WALL### 2 2 0 ###LEFT-WALL### 5 - 5 - 7 analysis 5 - 20 : 6 way 7 analysis 7 analysis 8 of 8 of 9 variance 9 variance 11 aging 10 ( 11 aging 11 aging 16 groups 11 aging 17 for 11 aging 19 ) 12 groups 13 and 13 and 15 age 13 and 16 groups 14 chronological 15 age 17 for 18 biomarkers 20 : 21 there 20 : 22 were 20 : 37 . 21 there 22 were 22 were 33 and 23 significant 24 differences 24 differences 25 of 24 differences 33 and 25 of 27 biomarkers 26 7 27 biomarkers 27 biomarkers 28 in 28 in 32 groups 29 different 31 age 30 chronological 31 age 31 age 32 groups 33 and 36 groups 34 different 36 groups 35 aging 36 groups [(] 3 [ )(a comparison of biomarkers among aging groups : there were significant differences in pp among 3 aging groups in 4 age groups . 0 ###LEFT-WALL### 2 3 0 ###LEFT-WALL### 13 were 0 ###LEFT-WALL### 26 . 2 3 5 comparison 2 3 11 : 2 3 13 were 4 )(a 5 comparison 5 comparison 6 of 5 comparison 11 : 6 of 7 biomarkers 7 biomarkers 8 among 8 among 9 aging 9 aging 10 groups 11 : 12 there 13 were 15 differences 13 were 16 in 14 significant 15 differences 16 in 17 pp 17 pp 18 among 17 pp 20 aging 18 among 19 3 20 aging 21 groups 20 aging 22 in 22 in 25 groups 23 4 25 groups 24 age 25 groups there were significant differences in edv among 3 aging groups in 4 age groups . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 were 0 ###LEFT-WALL### 15 . 1 there 2 were 2 were 4 differences 3 significant 4 differences 4 differences 5 in 4 differences 9 aging 5 in 6 edv 6 edv 7 among 7 among 8 3 9 aging 10 groups 10 groups 11 in 11 in 14 groups 12 4 14 groups 13 age 14 groups edv increased significantly in early aging group to normal aging group and delayed aging group . 0 ###LEFT-WALL### 1 edv 0 ###LEFT-WALL### 7 group 0 ###LEFT-WALL### 16 . 1 edv 2 increased 1 edv 7 group 2 increased 3 significantly 2 increased 4 in 4 in 6 aging 5 early 6 aging 7 group 8 to 8 to 12 and 9 normal 11 group 10 aging 11 group 11 group 12 and 12 and 15 group 13 delayed 15 group 14 aging 15 group there were significant changes in imt , mvel , e/a , cysc and fib among aging groups in different age groups . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 were 0 ###LEFT-WALL### 9 , 0 ###LEFT-WALL### 22 . 1 there 2 were 2 were 4 changes 3 significant 4 changes 4 changes 5 in 5 in 6 imt 6 imt 8 mvel 7 , 8 mvel 8 mvel 9 , 9 , 14 fib 9 , 21 groups 10 e/a 11 , 10 e/a 14 fib 12 cysc 13 and 13 and 14 fib 14 fib 15 among 14 fib 21 groups 15 among 16 aging 16 aging 17 groups 17 groups 18 in 18 in 20 age 19 different 20 age conclusion : [(] 1 [ )(biological age score plays an essential role in the evaluation of aging . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 8 score 2 : 9 plays 2 : 18 . 4 1 8 score 6 )(biological 7 age 7 age 8 score 8 score 9 plays 9 plays 12 role 9 plays 13 in 10 an 11 essential 10 an 12 role 11 essential 12 role 13 in 15 evaluation 14 the 15 evaluation 15 evaluation 16 of 16 of 17 aging based on individual evaluation [of] biological age [score] , the degrees of aging can be categorized by grouping so that a clinician may provide clinical anti - aging interventions within the target groups . 0 ###LEFT-WALL### 11 degrees 0 ###LEFT-WALL### 16 categorized 0 ###LEFT-WALL### 34 . 1 based 2 on 1 based 9 , 1 based 11 degrees 2 on 7 age 3 individual 4 evaluation 4 evaluation 7 age 6 biological 7 age 10 the 11 degrees 11 degrees 12 of 11 degrees 14 can 12 of 13 aging 14 can 15 be 15 be 16 categorized 16 categorized 17 by 16 categorized 20 that 17 by 18 grouping 19 so 20 that 20 that 22 clinician 20 that 24 provide 21 a 22 clinician 22 clinician 23 may 23 may 24 provide 24 provide 29 interventions 24 provide 30 within 25 clinical 29 interventions 26 anti 27 - 26 anti 29 interventions 28 aging 29 interventions 30 within 33 groups 31 the 33 groups 32 target 33 groups [(] 2 [ )( above 7 biomarkers are competent for the evaluation of aging . 0 ###LEFT-WALL### 2 2 0 ###LEFT-WALL### 8 are 0 ###LEFT-WALL### 15 . 2 2 5 above 2 2 8 are 5 above 7 biomarkers 6 7 7 biomarkers 8 are 9 competent 9 competent 10 for 10 for 12 evaluation 11 the 12 evaluation 12 evaluation 13 of 13 of 14 aging they can not only be used to construct biological age score equation , but also provide clinical targeted interventions for aging . 0 ###LEFT-WALL### 1 they 0 ###LEFT-WALL### 16 provide 0 ###LEFT-WALL### 22 . 1 they 2 can 2 can 4 only 3 not 4 only 4 only 5 be 4 only 14 but 5 be 6 used 6 used 7 to 6 used 8 construct 7 to 8 construct 8 construct 12 equation 9 biological 10 age 10 age 12 equation 11 score 12 equation 13 , 14 but 14 but 16 provide 15 also 16 provide 16 provide 19 interventions 17 clinical 19 interventions 18 targeted 19 interventions 19 interventions 20 for 20 for 21 aging [none] background : particulate air pollution has been associated with cardiovascular morbidity and mortality , but it remains unclear which time windows and pollutant sources are most critical . 0 ###LEFT-WALL### 2 background 0 ###LEFT-WALL### 3 : 0 ###LEFT-WALL### 9 associated 3 : 4 particulate 4 particulate 5 air 4 particulate 9 associated 5 air 6 pollution 5 air 8 been 5 air 9 associated 6 pollution 7 has 7 has 8 been 9 associated 10 with 10 with 13 and 11 cardiovascular 12 morbidity 12 morbidity 13 and 13 and 14 mortality 13 and 15 , 13 and 16 but 15 , 16 but 16 but 17 it 16 but 18 remains 16 but 26 are 16 but 29 . 18 remains 19 unclear 18 remains 26 are 19 unclear 20 which 20 which 21 time 21 time 25 sources 22 windows 23 and 23 and 24 pollutant 23 and 25 sources 26 are 28 critical 27 most 28 critical microrna ( mirna ) is thought to be involved in cardiovascular regulation . 0 ###LEFT-WALL### 1 microrna 0 ###LEFT-WALL### 6 thought 0 ###LEFT-WALL### 13 . 1 microrna 3 mirna 1 microrna 5 is 2 ( 3 mirna 3 mirna 4 ) 5 is 6 thought 6 thought 7 to 7 to 8 be 8 be 9 involved 9 involved 10 in 10 in 12 regulation 11 cardiovascular 12 regulation however , little is known about whether polymorphisms in genes that process micrornas influence response [to] pollutant exposure . 0 ###LEFT-WALL### 3 little 0 ###LEFT-WALL### 5 known 0 ###LEFT-WALL### 19 . 1 however 2 , 1 however 3 little 3 little 4 is 4 is 5 known 5 known 6 about 6 about 7 whether 7 whether 8 polymorphisms 7 whether 14 influence 8 polymorphisms 9 in 8 polymorphisms 14 influence 9 in 10 genes 10 genes 11 that 10 genes 12 process 11 that 12 process 12 process 13 micrornas 14 influence 18 exposure 15 response 18 exposure 17 pollutant 18 exposure we hypothesized that averaging times longer than routinely measured one or two day moving averages are associated with higher soluble intercellular adhesion molecule - 1 ( sicam - 1 ) and vascular cell adhesion molecule - 1 ( svcam - 1 ) levels , and that stationary and mobile sources contribute differently to these effects . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 hypothesized 1 we 2 hypothesized 2 hypothesized 31 and 3 that 4 averaging 3 that 31 and 4 averaging 5 times 4 averaging 6 longer 4 averaging 7 than 4 averaging 25 1 4 averaging 28 - 7 than 23 molecule 8 routinely 9 measured 9 measured 23 molecule 10 one 11 or 11 or 13 day 11 or 15 averages 11 or 18 with 11 or 23 molecule 12 two 13 day 14 moving 15 averages 15 averages 16 are 16 are 17 associated 17 associated 18 with 19 higher 22 adhesion 20 soluble 22 adhesion 21 intercellular 22 adhesion 22 adhesion 23 molecule 24 - 25 1 26 ( 28 - 27 sicam 28 - 28 - 29 1 28 - 30 ) 31 and 35 molecule 31 and 37 1 32 vascular 33 cell 33 cell 34 adhesion 34 adhesion 35 molecule 36 - 37 1 37 1 45 and 37 1 56 . 38 ( 45 and 39 svcam 41 1 39 svcam 43 levels 40 - 41 1 41 1 42 ) 43 levels 45 and 44 , 45 and 45 and 46 that 45 and 50 sources 45 and 51 contribute 45 and 56 . 47 stationary 48 and 48 and 49 mobile 48 and 50 sources 50 sources 51 contribute 51 contribute 52 differently 51 contribute 53 to 53 to 55 effects 54 these 55 effects we also investigated [whether] single nucleotide polymorphisms ( snps ) in mirna - processing genes modify these associations . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 investigated 0 ###LEFT-WALL### 13 - 1 we 3 investigated 2 also 3 investigated 3 investigated 7 polymorphisms 3 investigated 11 in 5 single 6 nucleotide 6 nucleotide 7 polymorphisms 7 polymorphisms 9 snps 8 ( 9 snps 9 snps 10 ) 11 in 12 mirna 13 - 15 genes 13 - 16 modify 13 - 19 . 14 processing 15 genes 15 genes 16 modify 16 modify 18 associations 17 these 18 associations methods : sicam - 1 [and] svcam - 1 were measured from 1999 - 2008 and matched to air pollution monitoring for fine particulate matter ( pm2.5 ) black carbon , and sulfates [(] so42 - ) . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 38 . 1 methods 2 : 2 : 3 sicam 3 sicam 7 svcam 4 - 7 svcam 5 1 7 svcam 7 svcam 9 1 7 svcam 37 ) 8 - 9 1 9 1 16 and 9 1 36 - 10 were 11 measured 10 were 16 and 11 measured 14 - 12 from 14 - 13 1999 14 - 14 - 15 2008 16 and 17 matched 16 and 18 to 18 to 32 and 19 air 20 pollution 19 air 32 and 20 pollution 21 monitoring 21 monitoring 22 for 21 monitoring 30 carbon 22 for 25 matter 23 fine 24 particulate 24 particulate 25 matter 25 matter 27 pm2.5 26 ( 27 pm2.5 27 pm2.5 28 ) 29 black 30 carbon 31 , 32 and 32 and 33 sulfates 32 and 35 so42 we selected 17 snps in five mirna - processing genes . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 selected 0 ###LEFT-WALL### 11 . 1 we 2 selected 2 selected 4 snps 2 selected 5 in 3 17 4 snps 5 in 10 genes 6 five 10 genes 7 mirna 8 - 7 mirna 10 genes 9 processing 10 genes mixed - effects models were used to assess effects of pollutants , snps , and interactions under recessive inheritance models using repeated measures . 0 ###LEFT-WALL### 4 models 0 ###LEFT-WALL### 6 used 0 ###LEFT-WALL### 24 . 1 mixed 2 - 1 mixed 4 models 3 effects 4 models 4 models 5 were 5 were 6 used 6 used 7 to 6 used 8 assess 7 to 8 assess 8 assess 9 effects 8 assess 17 under 8 assess 21 using 9 effects 10 of 10 of 15 and 11 pollutants 12 , 12 , 13 snps 12 , 15 and 14 , 15 and 15 and 16 interactions 17 under 20 models 18 recessive 19 inheritance 19 inheritance 20 models 21 using 23 measures 22 repeated 23 measures results : 723 participants with 1652 observations and 1 - 5 visits were included in our analyses for black carbon and pm2.5 . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 14 included 0 ###LEFT-WALL### 23 . 1 results 2 : 2 : 4 participants 3 723 4 participants 4 participants 5 with 5 with 7 observations 6 1652 7 observations 8 and 9 1 8 and 10 - 9 1 10 - 10 - 12 visits 11 5 12 visits 12 visits 13 were 13 were 14 included 14 included 15 in 15 in 17 analyses 16 our 17 analyses 17 analyses 18 for 18 for 21 and 19 black 20 carbon 20 carbon 21 and 21 and 22 pm2.5 sulfate data [was] available for 672 participants with 1390 observations . 0 ###LEFT-WALL### 1 sulfate 0 ###LEFT-WALL### 11 . 1 sulfate 2 data 2 data 4 available 4 available 5 for 4 available 8 with 5 for 7 participants 6 672 7 participants 8 with 10 observations 9 1390 10 observations interquartile range changes in [sulfates] ( 1.39 μg/m3 ) were associated with 1.4 % higher [(] 95%ci : 0.04 , 2.7 ) and 1.6 % ( 95%ci [:] - 0.4 , 3.7 ) higher sicam - 1 and [svcam] - 1 respectively . 0 ###LEFT-WALL### 1 interquartile 0 ###LEFT-WALL### 11 associated 0 ###LEFT-WALL### 43 . 1 interquartile 2 range 1 interquartile 3 changes 1 interquartile 8 μg/m3 1 interquartile 10 were 2 range 3 changes 3 changes 4 in 6 ( 8 μg/m3 7 1.39 8 μg/m3 8 μg/m3 9 ) 10 were 11 associated 11 associated 12 with 11 associated 42 respectively 12 with 25 % 12 with 38 and 13 1.4 14 % 13 1.4 23 and 14 % 17 95%ci 15 higher 17 95%ci 17 95%ci 18 : 18 : 19 0.04 19 0.04 21 2.7 20 , 21 2.7 21 2.7 22 ) 23 and 24 1.6 23 and 25 % 25 % 35 sicam 26 ( 35 sicam 27 95%ci 30 0.4 27 95%ci 35 sicam 29 - 30 0.4 30 0.4 32 3.7 30 0.4 33 ) 31 , 32 3.7 32 3.7 33 ) 34 higher 35 sicam 35 sicam 36 - 37 1 38 and 38 and 41 1 40 - 41 1 no significant associations were observed for black carbon . 0 ###LEFT-WALL### 3 associations 0 ###LEFT-WALL### 5 observed 0 ###LEFT-WALL### 9 . 1 no 3 associations 2 significant 3 associations 3 associations 4 were 4 were 5 observed 5 observed 6 for 6 for 8 carbon 7 black 8 carbon in interaction models with pm2.5 , both sicam - 1 and svcam - 1 levels were lower in rs1062923 homozygous carriers . 0 ###LEFT-WALL### 7 both 0 ###LEFT-WALL### 8 sicam 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 22 . 1 in 3 models 1 in 6 , 1 in 7 both 2 interaction 3 models 3 models 4 with 4 with 5 pm2.5 7 both 8 sicam 8 sicam 10 1 9 - 10 1 11 and 15 levels 11 and 16 were 12 svcam 13 - 12 svcam 15 levels 14 1 15 levels 15 levels 16 were 16 were 17 lower 17 lower 18 in 18 in 21 carriers 19 rs1062923 21 carriers 20 homozygous 21 carriers these interactions remained significant after multiple comparisons adjustment . 0 ###LEFT-WALL### 2 interactions 0 ###LEFT-WALL### 3 remained 0 ###LEFT-WALL### 9 . 1 these 2 interactions 2 interactions 3 remained 3 remained 4 significant 4 significant 5 after 5 after 8 adjustment 6 multiple 7 comparisons 7 comparisons 8 adjustment conclusions : pm2.5 seven day moving averages are associated with higher sicam - 1 and svcam - 1 levels . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 17 - 0 ###LEFT-WALL### 20 . 1 conclusions 2 : 2 : 15 and 3 pm2.5 4 seven 3 pm2.5 5 day 5 day 7 averages 5 day 8 are 5 day 9 associated 5 day 15 and 6 moving 7 averages 7 averages 8 are 9 associated 10 with 10 with 12 sicam 10 with 14 1 11 higher 12 sicam 13 - 14 1 15 and 16 svcam 17 - 19 levels 18 1 19 levels so4 - 2 seven day moving averages are associated with higher sicam - 1 and a suggestive association was observed with svcam - 1 in aging men . 0 ###LEFT-WALL### 7 averages 0 ###LEFT-WALL### 9 associated 0 ###LEFT-WALL### 15 and 0 ###LEFT-WALL### 28 . 1 so4 2 - 1 so4 7 averages 3 2 7 averages 4 seven 5 day 5 day 6 moving 6 moving 7 averages 7 averages 8 are 8 are 9 associated 9 associated 10 with 10 with 12 sicam 10 with 14 1 11 higher 12 sicam 13 - 14 1 15 and 18 association 15 and 20 observed 16 a 18 association 17 suggestive 18 association 18 association 19 was 19 was 20 observed 20 observed 21 with 21 with 27 men 22 svcam 27 men 23 - 24 1 24 1 25 in 25 in 27 men 26 aging 27 men snps in mirna - processing genes may modify associations between ambient pollution and sicam - 1 and [svcam] - 1 , which are [correlates] of atherosclerosis and cardiovascular disease . 0 ###LEFT-WALL### 5 processing 0 ###LEFT-WALL### 8 modify 0 ###LEFT-WALL### 21 , 0 ###LEFT-WALL### 30 . 1 snps 5 processing 2 in 3 mirna 2 in 4 - 2 in 5 processing 5 processing 6 genes 5 processing 7 may 7 may 8 modify 8 modify 9 associations 8 modify 10 between 10 between 13 and 11 ambient 12 pollution 12 pollution 13 and 13 and 14 sicam 14 sicam 17 and 15 - 16 1 16 1 17 and 17 and 20 1 19 - 20 1 21 , 22 which 21 , 23 are 22 which 23 are 23 are 25 of 25 of 27 and 26 atherosclerosis 27 and 27 and 29 disease 28 cardiovascular 29 disease background : the high mortality of hip fracture patients is well documented , but sex - and cause - specific mortality [after] [hip] [fracture] has not been extensively studied . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 4 high 2 : 12 documented 3 the 4 high 4 high 5 mortality 4 high 10 is 4 high 12 documented 5 mortality 6 of 5 mortality 10 is 6 of 9 patients 7 hip 9 patients 8 fracture 9 patients 11 well 12 documented 12 documented 21 mortality 12 documented 29 studied 13 , 14 but 14 but 17 and 14 but 19 - 14 but 21 mortality 15 sex 17 and 16 - 17 and 17 and 18 cause 17 and 19 - 20 specific 21 mortality 21 mortality 25 has 25 has 26 not 25 has 27 been 27 been 29 studied 28 extensively 29 studied 29 studied 30 . the purpose of the present study was to evaluate mortality and cause of death in patients after hip fracture surgery and to compare their mortality and cause of death to those in the general population . 0 ###LEFT-WALL### 2 purpose 0 ###LEFT-WALL### 36 . 1 the 2 purpose 2 purpose 3 of 2 purpose 7 was 3 of 6 study 4 the 6 study 5 present 6 study 7 was 8 to 7 was 21 and 8 to 21 and 9 evaluate 11 and 9 evaluate 15 in 9 evaluate 17 after 9 evaluate 21 and 10 mortality 11 and 11 and 12 cause 11 and 13 of 13 of 14 death 15 in 16 patients 17 after 20 surgery 18 hip 20 surgery 19 fracture 20 surgery 21 and 22 to 21 and 23 compare 21 and 32 in 22 to 23 compare 23 compare 26 and 23 compare 30 to 24 their 25 mortality 25 mortality 26 and 26 and 27 cause 26 and 28 of 28 of 29 death 30 to 31 those 32 in 35 population 33 the 35 population 34 general 35 population methods : records of 428 consecutive hip fracture patients were collected on a population - basis and data on the general population comprising all finns 65 years of age or older were collected on a cohort - basis . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 3 records 2 : 10 were 2 : 15 - 2 : 37 - 3 records 4 of 3 records 10 were 4 of 9 patients 5 428 9 patients 6 consecutive 9 patients 7 hip 9 patients 8 fracture 9 patients 10 were 11 collected 11 collected 12 on 12 on 14 population 13 a 14 population 15 - 16 basis 15 - 17 and 17 and 18 data 17 and 32 were 18 data 19 on 18 data 23 comprising 18 data 32 were 19 on 22 population 20 the 22 population 21 general 22 population 23 comprising 25 finns 23 comprising 30 or 24 all 25 finns 26 65 27 years 27 years 28 of 27 years 30 or 28 of 29 age 30 or 31 older 32 were 33 collected 33 collected 34 on 34 on 36 cohort 35 a 36 cohort 37 - 38 basis 37 - 39 . cause of death was classified as [follows] [:] malignant neoplasms , dementia , circulatory disease , respiratory disease , digestive system disease , and other . 0 ###LEFT-WALL### 1 cause 0 ###LEFT-WALL### 4 was 0 ###LEFT-WALL### 26 . 1 cause 2 of 1 cause 4 was 2 of 3 death 4 was 24 and 5 classified 10 neoplasms 6 as 9 malignant 9 malignant 10 neoplasms 10 neoplasms 11 , 11 , 15 disease 11 , 16 , 12 dementia 13 , 12 dementia 15 disease 14 circulatory 15 disease 16 , 18 disease 16 , 19 , 17 respiratory 18 disease 19 , 22 disease 19 , 24 and 20 digestive 21 system 21 system 22 disease 23 , 24 and 24 and 25 other results : mean follow - up [was] 3.7 years ( range 0 - 9 years ) . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 4 follow 2 : 17 . 3 mean 4 follow 4 follow 6 up 5 - 6 up 6 up 9 years 6 up 16 ) 8 3.7 9 years 9 years 11 range 10 ( 11 range 11 range 12 0 11 range 15 years 11 range 16 ) 13 - 15 years 14 9 15 years 15 years 16 ) overall 1 [-] year postoperative mortality was 27.3 % and mortality [after] hip fracture at the end of [the] [follow] - up was 79.0 % . 0 ###LEFT-WALL### 1 overall 0 ###LEFT-WALL### 23 was 0 ###LEFT-WALL### 26 . 1 overall 10 and 1 overall 14 fracture 1 overall 23 was 2 1 4 year 4 year 6 mortality 4 year 7 was 4 year 10 and 5 postoperative 6 mortality 6 mortality 7 was 7 was 9 % 8 27.3 9 % 10 and 13 hip 10 and 14 fracture 11 mortality 13 hip 14 fracture 15 at 15 at 17 end 16 the 17 end 17 end 18 of 18 of 22 up 21 - 22 up 23 was 25 % 24 79.0 25 % during the [follow] [-] up , age - adjusted mortality after hip fracture surgery was higher in men than in women with hazard [ratio] ( hr ) 1.55 and 95 % confidence [interval] ( 95 % ci ) 1.21 - 2.00 . 0 ###LEFT-WALL### 10 mortality 0 ###LEFT-WALL### 15 was 0 ###LEFT-WALL### 42 . 1 during 7 age 1 during 8 - 1 during 10 mortality 2 the 7 age 5 up 6 , 5 up 7 age 9 adjusted 10 mortality 10 mortality 11 after 10 mortality 15 was 11 after 14 surgery 12 hip 13 fracture 13 fracture 14 surgery 15 was 16 higher 16 higher 17 in 16 higher 19 than 16 higher 22 with 16 higher 40 - 17 in 18 men 19 than 20 in 20 in 21 women 22 with 23 hazard 22 with 32 confidence 23 hazard 26 hr 25 ( 26 hr 26 hr 27 ) 28 1.55 29 and 29 and 30 95 29 and 31 % 31 % 32 confidence 32 confidence 37 ci 34 ( 37 ci 35 95 37 ci 36 % 37 ci 37 ci 38 ) 39 1.21 40 - 40 - 41 2.00 among hip surgery patients , the most common causes of death were circulatory diseases , followed by dementia and alzheimer 's disease . 0 ###LEFT-WALL### 9 causes 0 ###LEFT-WALL### 15 , 0 ###LEFT-WALL### 23 . 1 among 4 patients 1 among 5 , 1 among 9 causes 2 hip 3 surgery 3 surgery 4 patients 6 the 7 most 7 most 9 causes 8 common 9 causes 9 causes 10 of 9 causes 15 , 10 of 11 death 12 were 14 diseases 12 were 15 , 13 circulatory 14 diseases 15 , 16 followed 15 , 17 by 17 by 19 and 18 dementia 19 and 19 and 22 disease 20 alzheimer 21 's 21 's 22 disease [after] hip fracture , men were more likely than women to die from respiratory disease , malignant neoplasm , and circulatory disease . 0 ###LEFT-WALL### 3 fracture 0 ###LEFT-WALL### 4 , 0 ###LEFT-WALL### 23 . 2 hip 3 fracture 4 , 5 men 4 , 6 were 5 men 6 were 6 were 8 likely 7 more 8 likely 8 likely 9 than 8 likely 11 to 8 likely 12 die 9 than 10 women 11 to 12 die 12 die 13 from 13 from 20 and 14 respiratory 15 disease 15 disease 16 , 16 , 18 neoplasm 16 , 20 and 17 malignant 18 neoplasm 19 , 20 and 20 and 22 disease 21 circulatory 22 disease [during] [the] follow - up , all - cause age - and sex - standardized mortality after hip fracture [was] 3 - fold higher than that of the general population and included every cause - [of] - death category . 0 ###LEFT-WALL### 3 follow 0 ###LEFT-WALL### 37 - 3 follow 5 up 3 follow 7 all 3 follow 9 cause 4 - 5 up 5 up 6 , 8 - 9 cause 9 cause 12 and 9 cause 31 and 9 cause 35 - 10 age 12 and 11 - 12 and 12 and 13 sex 12 and 16 mortality 12 and 31 and 14 - 16 mortality 15 standardized 16 mortality 16 mortality 17 after 16 mortality 22 - 17 after 19 fracture 18 hip 19 fracture 19 fracture 21 3 23 fold 24 higher 23 fold 25 than 23 fold 31 and 25 than 26 that 25 than 27 of 27 of 30 population 28 the 30 population 29 general 30 population 31 and 32 included 31 and 34 cause 33 every 34 cause 37 - 39 category 37 - 40 . 38 death 39 category conclusion : during the study period , the risk of mortality in hip fracture patients was 3 - fold higher than that in the general population and included every major cause of death . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 7 , 1 conclusion 2 : 2 : 3 during 3 during 6 period 4 the 6 period 5 study 6 period 7 , 9 risk 7 , 16 was 7 , 18 - 8 the 9 risk 9 risk 10 of 9 risk 16 was 10 of 11 mortality 11 mortality 12 in 12 in 15 patients 13 hip 15 patients 14 fracture 15 patients 16 was 17 3 18 - 27 and 18 - 34 . 19 fold 20 higher 19 fold 21 than 19 fold 23 in 19 fold 27 and 21 than 22 that 23 in 26 population 24 the 26 population 25 general 26 population 27 and 28 included 28 included 31 cause 29 every 31 cause 30 major 31 cause 31 cause 32 of 32 of 33 death the population is aging , the prevalence of heart failure increases with age , and on average women live longer than men . 0 ###LEFT-WALL### 2 population 0 ###LEFT-WALL### 3 is 0 ###LEFT-WALL### 5 , 0 ###LEFT-WALL### 23 . 1 the 2 population 2 population 3 is 3 is 4 aging 5 , 7 prevalence 5 , 11 increases 6 the 7 prevalence 7 prevalence 8 of 7 prevalence 11 increases 8 of 10 failure 9 heart 10 failure 11 increases 15 and 12 with 13 age 12 with 15 and 14 , 15 and 15 and 16 on 16 on 18 women 17 average 18 women 18 women 19 live 19 live 20 longer 19 live 21 than 21 than 22 men there is evidence for sex - specific effects of individual , guideline [-] recommended drugs used for treatment of chronic heart failure . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 is 1 there 2 is 2 is 3 evidence 3 evidence 4 for 3 evidence 8 effects 4 for 5 sex 6 - 8 effects 7 specific 8 effects 8 effects 9 of 8 effects 23 . 9 of 15 drugs 10 individual 11 , 10 individual 15 drugs 12 guideline 14 recommended 14 recommended 15 drugs 15 drugs 16 used 16 used 17 for 17 for 18 treatment 18 treatment 19 of 19 of 22 failure 20 chronic 21 heart 21 heart 22 failure women are underrepresented in most clinical trials and only a minority of drug applications to regulatory authorities have included sex analyses . 0 ###LEFT-WALL### 1 women 0 ###LEFT-WALL### 2 are 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 22 . 1 women 2 are 2 are 3 underrepresented 3 underrepresented 4 in 4 in 7 trials 5 most 6 clinical 6 clinical 7 trials 8 and 9 only 8 and 14 applications 8 and 19 included 10 a 11 minority 11 minority 12 of 11 minority 14 applications 12 of 14 applications 13 drug 14 applications 14 applications 15 to 14 applications 18 have 15 to 17 authorities 16 regulatory 17 authorities 18 have 19 included 19 included 21 analyses 20 sex 21 analyses the present review focuses on the potential female survival benefit in heart failure , the influence of sex on medical treatment in a broader sense , and the potential benefit to be derived from guideline recommended treatment and common adjunctive heart failure medication . 0 ###LEFT-WALL### 3 review 0 ###LEFT-WALL### 4 focuses 0 ###LEFT-WALL### 14 , 0 ###LEFT-WALL### 44 . 1 the 3 review 2 present 3 review 3 review 4 focuses 4 focuses 5 on 4 focuses 11 in 5 on 10 benefit 6 the 10 benefit 7 potential 10 benefit 8 female 9 survival 9 survival 10 benefit 11 in 13 failure 12 heart 13 failure 14 , 27 and 14 , 33 derived 15 the 16 influence 16 influence 17 of 16 influence 19 on 16 influence 27 and 17 of 18 sex 19 on 21 treatment 20 medical 21 treatment 21 treatment 22 in 22 in 25 sense 23 a 25 sense 24 broader 25 sense 26 , 27 and 27 and 29 potential 27 and 30 benefit 28 the 29 potential 30 benefit 31 to 31 to 32 be 32 be 33 derived 33 derived 34 from 34 from 38 and 35 guideline 36 recommended 36 recommended 37 treatment 37 treatment 38 and 38 and 43 medication 39 common 43 medication 40 adjunctive 43 medication 41 heart 43 medication 42 failure 43 medication background/aims : difficulties with bathing are frequent among older people and [are] [associated] with an increasing need for societal support . 0 ###LEFT-WALL### 1 background/aims 0 ###LEFT-WALL### 2 : 2 : 3 difficulties 2 : 6 are 2 : 21 . 3 difficulties 4 with 3 difficulties 6 are 4 with 5 bathing 6 are 7 frequent 7 frequent 11 and 8 among 10 people 8 among 11 and 9 older 10 people 11 and 14 with 14 with 17 need 15 an 17 need 16 increasing 17 need 17 need 18 for 18 for 20 support 19 societal 20 support as loss of independence has a negative impact on health and wellbeing , it is important to study interventions that can provide the required support for people to be able to remain independent . 0 ###LEFT-WALL### 14 it 0 ###LEFT-WALL### 15 is 0 ###LEFT-WALL### 34 . 1 as 2 loss 1 as 5 has 1 as 14 it 2 loss 3 of 2 loss 5 has 3 of 4 independence 5 has 8 impact 6 a 8 impact 7 negative 8 impact 9 on 11 and 9 on 13 , 9 on 14 it 10 health 11 and 11 and 12 wellbeing 14 it 15 is 15 is 16 important 16 important 17 to 16 important 28 to 16 important 29 be 17 to 18 study 18 study 19 interventions 18 study 26 for 19 interventions 20 that 19 interventions 22 provide 20 that 21 can 21 can 22 provide 22 provide 25 support 23 the 25 support 24 required 25 support 26 for 27 people 28 to 29 be 29 be 30 able 30 able 31 to 31 to 32 remain 32 remain 33 independent occupational therapy interventions can improve clients ' abilities enabling them to bathe themselves , thus reducing the need for other [,] more long - term societal support [from] , e.g . [a] home help . 0 ###LEFT-WALL### 3 interventions 0 ###LEFT-WALL### 5 improve 0 ###LEFT-WALL### 29 , 0 ###LEFT-WALL### 31 . 1 occupational 2 therapy 2 therapy 3 interventions 3 interventions 4 can 4 can 5 improve 5 improve 8 abilities 5 improve 16 reducing 6 clients 7 ' 7 ' 8 abilities 8 abilities 9 enabling 8 abilities 11 to 8 abilities 12 bathe 9 enabling 10 them 11 to 12 bathe 12 bathe 13 themselves 14 , 16 reducing 15 thus 16 reducing 16 reducing 18 need 16 reducing 19 for 16 reducing 29 , 17 the 18 need 19 for 27 support 20 other 27 support 22 more 23 long 23 long 24 - 23 long 25 term 25 term 27 support 26 societal 27 support 29 , 30 e.g 31 . 33 home 31 . 35 . 33 home 34 help in this study , two groups of elderly people with difficulties in bathing were compared ; the clients in the intervention group were engaged in occupational therapy . 0 ###LEFT-WALL### 6 groups 0 ###LEFT-WALL### 15 compared 0 ###LEFT-WALL### 16 ; 0 ###LEFT-WALL### 28 . 1 in 3 study 1 in 4 , 1 in 6 groups 2 this 3 study 5 two 6 groups 6 groups 7 of 6 groups 14 were 7 of 9 people 8 elderly 9 people 9 people 10 with 10 with 11 difficulties 11 difficulties 12 in 12 in 13 bathing 14 were 15 compared 16 ; 18 clients 16 ; 23 were 17 the 18 clients 18 clients 19 in 18 clients 23 were 19 in 22 group 20 the 22 group 21 intervention 22 group 23 were 24 engaged 24 engaged 25 in 25 in 27 therapy 26 occupational 27 therapy methods : a quasi [-] experimental [non] - equivalent control group design was used , in which participants with reported difficulties in bathing were recruited consecutively from two municipalities . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 1 methods 2 : 2 : 9 equivalent 3 a 9 equivalent 4 quasi 9 equivalent 6 experimental 8 - 6 experimental 9 equivalent 9 equivalent 10 control 9 equivalent 14 used 9 equivalent 16 in 10 control 12 design 10 control 13 was 10 control 14 used 11 group 12 design 12 design 13 was 15 , 16 in 16 in 17 which 16 in 18 participants 16 in 25 recruited 16 in 30 . 18 participants 19 with 18 participants 24 were 19 with 21 difficulties 20 reported 21 difficulties 21 difficulties 22 in 22 in 23 bathing 24 were 25 recruited 25 recruited 26 consecutively 25 recruited 27 from 27 from 29 municipalities 28 two 29 municipalities the clients in the intervention group routinely received occupational therapy , whereas clients in the control group received assistance from a home help for bathing . 0 ###LEFT-WALL### 2 clients 0 ###LEFT-WALL### 23 help 0 ###LEFT-WALL### 26 . 1 the 2 clients 2 clients 3 in 2 clients 6 group 3 in 5 intervention 4 the 5 intervention 6 group 10 therapy 6 group 12 whereas 7 routinely 8 received 8 received 10 therapy 9 occupational 10 therapy 11 , 12 whereas 12 whereas 13 clients 13 clients 14 in 13 clients 20 from 13 clients 23 help 14 in 19 assistance 15 the 19 assistance 16 control 18 received 17 group 18 received 18 received 19 assistance 20 from 22 home 21 a 22 home 23 help 24 for 24 for 25 bathing activities of daily living , quality of life and home - help allocation were assessed at the baseline and after 15 weeks . 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 11 - 1 activities 2 of 1 activities 5 , 2 of 4 living 3 daily 4 living 5 , 6 quality 5 , 9 and 6 quality 7 of 7 of 8 life 9 and 10 home 11 - 13 allocation 11 - 15 assessed 11 - 23 . 12 help 13 allocation 13 allocation 14 were 14 were 15 assessed 15 assessed 19 and 16 at 18 baseline 16 at 19 and 17 the 18 baseline 19 and 20 after 20 after 22 weeks 21 15 22 weeks results : clients in the intervention group received less than three home visits on average , with majority of interventions consisting of graded activity and the use of an encouraging approach . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 10 than 1 results 2 : 2 : 3 clients 2 : 4 in 4 in 7 group 5 the 7 group 6 intervention 7 group 7 group 8 received 8 received 9 less 10 than 11 three 10 than 12 home 11 three 12 home 12 home 13 visits 12 home 15 average 12 home 17 with 14 on 15 average 16 , 17 with 17 with 25 and 17 with 32 . 18 majority 19 of 18 majority 25 and 19 of 20 interventions 20 interventions 21 consisting 21 consisting 22 of 22 of 24 activity 23 graded 24 activity 25 and 27 use 25 and 28 of 26 the 27 use 28 of 31 approach 29 an 31 approach 30 encouraging 31 approach seventy per cent of the interventions were adaptive . 0 ###LEFT-WALL### 1 seventy 0 ###LEFT-WALL### 7 were 0 ###LEFT-WALL### 9 . 1 seventy 2 per 1 seventy 4 of 1 seventy 7 were 2 per 3 cent 4 of 6 interventions 5 the 6 interventions 7 were 8 adaptive activities of daily living and quality of life of both groups improved , but the differences of being allocated [a] home help were significant . 0 ###LEFT-WALL### 5 and 0 ###LEFT-WALL### 12 improved 0 ###LEFT-WALL### 14 but 0 ###LEFT-WALL### 25 . 1 activities 2 of 1 activities 5 and 2 of 4 living 3 daily 4 living 5 and 6 quality 5 and 12 improved 6 quality 7 of 6 quality 9 of 7 of 8 life 9 of 11 groups 10 both 11 groups 13 , 14 but 14 but 16 differences 14 but 23 were 15 the 16 differences 16 differences 17 of 16 differences 23 were 17 of 18 being 18 being 22 help 19 allocated 22 help 21 home 22 help 23 were 24 significant conclusion : occupational therapy interventions seem beneficial in terms of supporting older people in becoming independent of home help in bathing but the results must be interpreted with caution as there were differences at baseline between the groups . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 3 occupational 2 : 32 were 2 : 39 . 3 occupational 4 therapy 3 occupational 9 terms 3 occupational 10 of 3 occupational 14 in 3 occupational 17 of 3 occupational 32 were 4 therapy 5 interventions 4 therapy 8 in 4 therapy 9 terms 5 interventions 6 seem 6 seem 7 beneficial 7 beneficial 8 in 10 of 13 people 11 supporting 13 people 12 older 13 people 14 in 15 becoming 15 becoming 16 independent 17 of 18 home 18 home 19 help 18 home 26 be 18 home 27 interpreted 19 help 20 in 19 help 22 but 19 help 25 must 20 in 21 bathing 22 but 24 results 23 the 24 results 25 must 26 be 27 interpreted 28 with 27 interpreted 30 as 28 with 29 caution 30 as 31 there 32 were 33 differences 32 were 34 at 34 at 35 baseline 35 baseline 36 between 36 between 38 groups 37 the 38 groups introduction : one of the major contributions to skin photoageing and diseases is oxidative stress , caused by uv radiation inducing reactive oxygen and nitrogen species . 0 ###LEFT-WALL### 1 introduction 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 27 . 2 : 3 one 2 : 16 , 3 one 4 of 3 one 16 , 4 of 7 contributions 5 the 7 contributions 6 major 7 contributions 7 contributions 8 to 8 to 11 and 9 skin 10 photoageing 10 photoageing 11 and 11 and 12 diseases 13 is 15 stress 13 is 16 , 14 oxidative 15 stress 16 , 17 caused 16 , 18 by 18 by 24 and 19 uv 20 radiation 20 radiation 21 inducing 20 radiation 24 and 21 inducing 23 oxygen 22 reactive 23 oxygen 24 and 26 species 25 nitrogen 26 species successful prophylaxis and therapy would necessitate control of the oxidant/antioxidant balance at the affected site , which can be achieved through the external supply of endogenous antioxidants . 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 6 necessitate 0 ###LEFT-WALL### 16 , 0 ###LEFT-WALL### 28 . 1 successful 2 prophylaxis 2 prophylaxis 3 and 3 and 4 therapy 3 and 5 would 5 would 6 necessitate 6 necessitate 7 control 6 necessitate 12 at 7 control 8 of 8 of 11 balance 9 the 11 balance 10 oxidant/antioxidant 11 balance 12 at 15 site 13 the 15 site 14 affected 15 site 16 , 17 which 16 , 20 achieved 17 which 18 can 18 can 19 be 19 be 20 achieved 20 achieved 21 through 21 through 24 supply 22 the 24 supply 23 external 24 supply 24 supply 25 of 25 of 27 antioxidants 26 endogenous 27 antioxidants areas covered : this review discusses possible strategies for dermal delivery of the antioxidant vitamins [e] and [c] , as oral supplementation has proved insufficient . 0 ###LEFT-WALL### 2 covered 0 ###LEFT-WALL### 3 : 1 areas 2 covered 3 : 5 review 3 : 6 discusses 3 : 17 and 3 : 24 proved 3 : 26 . 4 this 5 review 5 review 6 discusses 6 discusses 8 strategies 7 possible 8 strategies 8 strategies 9 for 9 for 11 delivery 10 dermal 11 delivery 11 delivery 12 of 12 of 15 vitamins 13 the 15 vitamins 14 antioxidant 15 vitamins 17 and 19 , 17 and 22 supplementation 17 and 24 proved 20 as 21 oral 21 oral 22 supplementation 22 supplementation 23 has 23 has 24 proved 24 proved 25 insufficient these antioxidants have low skin bioavailability , owing to their poor solubility , inefficient skin permeability , or instability during storage . 0 ###LEFT-WALL### 2 antioxidants 0 ###LEFT-WALL### 3 have 0 ###LEFT-WALL### 13 , 0 ###LEFT-WALL### 22 . 1 these 2 antioxidants 2 antioxidants 3 have 3 have 6 bioavailability 4 low 5 skin 5 skin 6 bioavailability 6 bioavailability 8 owing 7 , 8 owing 8 owing 9 to 8 owing 12 solubility 8 owing 13 , 9 to 11 poor 10 their 11 poor 13 , 18 or 14 inefficient 15 skin 15 skin 16 permeability 16 permeability 18 or 17 , 18 or 18 or 19 instability 18 or 20 during 20 during 21 storage these drawbacks can be overcome by various approaches , such as chemical modification of the vitamins and the use of new colloidal drug delivery systems . 0 ###LEFT-WALL### 2 drawbacks 0 ###LEFT-WALL### 5 overcome 0 ###LEFT-WALL### 9 , 0 ###LEFT-WALL### 26 . 1 these 2 drawbacks 2 drawbacks 3 can 3 can 4 be 4 be 5 overcome 5 overcome 6 by 6 by 8 approaches 7 various 8 approaches 9 , 17 and 10 such 13 modification 11 as 12 chemical 12 chemical 13 modification 13 modification 14 of 13 modification 17 and 14 of 16 vitamins 15 the 16 vitamins 17 and 19 use 17 and 20 of 18 the 19 use 20 of 25 systems 21 new 23 drug 22 colloidal 23 drug 23 drug 25 systems 24 delivery 25 systems new knowledge is included about the importance of : enhancing the endogenous skin antioxidant defense through external supply ; the balance between various skin antioxidants ; factors that can improve the skin bioavailability of antioxidants ; and new delivery systems , such as microemulsions , used to deliver vitamins c and [e] [into] the skin simultaneously . 0 ###LEFT-WALL### 1 new 0 ###LEFT-WALL### 9 : 0 ###LEFT-WALL### 19 ; 0 ###LEFT-WALL### 57 . 1 new 2 knowledge 1 new 8 of 1 new 9 : 2 knowledge 3 is 3 is 4 included 4 included 5 about 5 about 7 importance 6 the 7 importance 7 importance 8 of 9 : 10 enhancing 10 enhancing 15 defense 10 enhancing 16 through 11 the 15 defense 12 endogenous 13 skin 13 skin 15 defense 14 antioxidant 15 defense 16 through 18 supply 17 external 18 supply 19 ; 21 balance 19 ; 25 antioxidants 19 ; 26 ; 20 the 21 balance 21 balance 22 between 21 balance 25 antioxidants 22 between 24 skin 23 various 24 skin 26 ; 27 factors 26 ; 30 improve 26 ; 36 ; 27 factors 28 that 27 factors 29 can 27 factors 30 improve 28 that 29 can 30 improve 33 bioavailability 31 the 33 bioavailability 32 skin 33 bioavailability 33 bioavailability 34 of 34 of 35 antioxidants 36 ; 37 and 37 and 40 systems 37 and 46 used 38 new 39 delivery 39 delivery 40 systems 40 systems 43 as 40 systems 46 used 41 , 43 as 42 such 43 as 43 as 44 microemulsions 43 as 45 , 46 used 47 to 46 used 48 deliver 47 to 48 deliver 48 deliver 49 vitamins 48 deliver 51 and 48 deliver 56 simultaneously 49 vitamins 50 c 51 and 55 skin 54 the 55 skin expert opinion : a promising strategy for enhancing skin protection from oxidative stress is to support the endogenous antioxidant system , with antioxidants containing products that are normally present in the skin . 0 ###LEFT-WALL### 2 opinion 0 ###LEFT-WALL### 3 : 0 ###LEFT-WALL### 16 support 1 expert 2 opinion 3 : 6 strategy 4 a 5 promising 4 a 6 strategy 5 promising 6 strategy 6 strategy 7 for 6 strategy 10 protection 6 strategy 16 support 7 for 8 enhancing 8 enhancing 9 skin 10 protection 11 from 10 protection 14 is 11 from 13 stress 12 oxidative 13 stress 14 is 15 to 14 is 16 support 15 to 16 support 16 support 20 system 16 support 22 with 17 the 20 system 18 endogenous 19 antioxidant 19 antioxidant 20 system 21 , 22 with 22 with 23 antioxidants 22 with 24 containing 22 with 33 . 24 containing 25 products 24 containing 30 in 25 products 26 that 25 products 27 are 26 that 27 are 27 are 29 present 28 normally 29 present 30 in 32 skin 31 the 32 skin purpose : epidemiological evidence suggests that ultraviolet ( uv ) irradiation and oxidative stress play an important role in age - related cataract pathogenesis . 0 ###LEFT-WALL### 1 purpose 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 25 . 2 : 4 evidence 2 : 5 suggests 2 : 22 related 3 epidemiological 4 evidence 4 evidence 5 suggests 5 suggests 6 that 6 that 12 and 6 that 15 play 7 ultraviolet 9 uv 7 ultraviolet 10 ) 7 ultraviolet 11 irradiation 8 ( 9 uv 9 uv 10 ) 11 irradiation 12 and 12 and 14 stress 12 and 15 play 13 oxidative 14 stress 15 play 18 role 15 play 19 in 16 an 18 role 17 important 18 role 19 in 20 age 21 - 22 related 22 related 24 pathogenesis 23 cataract 24 pathogenesis uv irradiation and oxidative stress can produce a wide range of dna damage . 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 7 produce 0 ###LEFT-WALL### 14 . 1 uv 2 irradiation 2 irradiation 3 and 3 and 5 stress 3 and 6 can 4 oxidative 5 stress 6 can 7 produce 7 produce 10 range 8 a 9 wide 8 a 10 range 9 wide 10 range 10 range 11 of 11 of 13 damage 12 dna 13 damage polymorphisms of dna repair enzymes may affect repair efficiency and the role of dna repair mechanisms has received attention recently in age - related cataract pathogenesis . 0 ###LEFT-WALL### 4 repair 0 ###LEFT-WALL### 17 has 0 ###LEFT-WALL### 24 related 0 ###LEFT-WALL### 27 . 1 polymorphisms 2 of 1 polymorphisms 4 repair 2 of 3 dna 4 repair 5 enzymes 4 repair 7 affect 4 repair 17 has 5 enzymes 6 may 6 may 7 affect 7 affect 10 and 8 repair 9 efficiency 9 efficiency 10 and 10 and 12 role 10 and 13 of 11 the 12 role 13 of 16 mechanisms 14 dna 15 repair 15 repair 16 mechanisms 17 has 19 attention 17 has 20 recently 17 has 21 in 18 received 19 attention 21 in 22 age 23 - 24 related 24 related 26 pathogenesis 25 cataract 26 pathogenesis in this case - control study , the aim was to determine the frequency of polymorphisms in two dna repair enzyme genes [,] xeroderma pigmentosum complementation group d ( xpd [ )(codon 751 and x - ray cross - complementing group 1 ( xrcc1 [ )(codon 399 , in patients with age - related cataract and [in] healthy controls . 1 in 3 case 1 in 9 aim 2 this 3 case 3 case 6 study 4 - 6 study 5 control 6 study 6 study 7 , 7 , 8 the 8 the 9 aim 9 aim 10 was 10 was 11 to 10 was 12 determine 11 to 12 determine 12 determine 14 frequency 12 determine 17 in 13 the 14 frequency 14 frequency 15 of 15 of 16 polymorphisms 17 in 27 group 18 two 27 group 19 dna 20 repair 20 repair 21 enzyme 21 enzyme 25 pigmentosum 22 genes 25 pigmentosum 24 xeroderma 25 pigmentosum 25 pigmentosum 26 complementation 26 complementation 27 group 27 group 28 d 27 group 34 and 27 group 39 - 29 ( 34 and 30 xpd 32 )(codon 32 )(codon 33 751 32 )(codon 34 and 34 and 35 x 34 and 36 - 36 - 39 - 37 ray 38 cross 38 cross 39 - 39 - 41 group 40 complementing 41 group 41 group 42 1 41 group 46 )(codon 41 group 49 in 43 ( 46 )(codon 44 xrcc1 46 )(codon 46 )(codon 47 399 46 )(codon 48 , 48 , 49 in 49 in 50 patients 49 in 60 . 50 patients 51 with 50 patients 59 controls 51 with 52 age 53 - 59 controls 54 related 55 cataract 55 cataract 56 and 56 and 58 healthy 56 and 59 controls 59 controls 60 . methods : polymerase chain reaction and restriction fragment length polymorphisms were used to analyze xpd t751g and xrcc1 g399a in 180 patients with age - related cataract [and] 174 healthy individuals as controls . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 17 and 2 : 26 related 2 : 34 . 3 polymerase 4 chain 4 chain 5 reaction 5 reaction 6 and 6 and 9 length 6 and 10 polymorphisms 6 and 14 analyze 6 and 17 and 7 restriction 8 fragment 8 fragment 9 length 10 polymorphisms 11 were 11 were 12 used 12 used 13 to 12 used 14 analyze 13 to 14 analyze 14 analyze 16 t751g 15 xpd 16 t751g 17 and 19 g399a 18 xrcc1 19 g399a 19 g399a 20 in 20 in 22 patients 21 180 22 patients 22 patients 23 with 23 with 24 age 25 - 26 related 26 related 31 individuals 27 cataract 31 individuals 29 174 31 individuals 30 healthy 31 individuals 31 individuals 32 as 32 as 33 controls results : there was a significant difference between the case and control groups in the xrcc1399 genotype . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 18 . 2 : 3 there 2 : 4 was 3 there 4 was 4 was 7 difference 5 a 6 significant 5 a 7 difference 6 significant 7 difference 7 difference 8 between 8 between 11 and 9 the 10 case 10 case 11 and 11 and 12 control 11 and 13 groups 11 and 17 genotype 13 groups 14 in 13 groups 17 genotype 14 in 16 xrcc1399 15 the 16 xrcc1399 the odds ratio of the xrcc1 g/a polymorphism compared with the g/g wild - type [genotype] was 1.92 ( 95 % ci = 1.17 - 3.15 , p = 0.01 ) . 0 ###LEFT-WALL### 3 ratio 0 ###LEFT-WALL### 17 was 0 ###LEFT-WALL### 32 . 1 the 3 ratio 2 odds 3 ratio 3 ratio 4 of 3 ratio 17 was 4 of 8 polymorphism 5 the 8 polymorphism 6 xrcc1 7 g/a 7 g/a 8 polymorphism 8 polymorphism 9 compared 9 compared 10 with 10 with 15 type 11 the 15 type 12 g/g 15 type 13 wild 14 - 13 wild 15 type 17 was 18 1.92 18 1.92 21 % 19 ( 21 % 20 95 21 % 21 % 22 ci 21 % 23 = 21 % 31 ) 22 ci 23 = 23 = 25 - 23 = 29 = 24 1.17 25 - 25 - 26 3.15 27 , 29 = 28 p 29 = 29 = 30 0.01 29 = 31 ) no statistically significant difference was found in the genotypic and allelic distributions of the polymorphisms in the xpd gene between the groups . 0 ###LEFT-WALL### 4 difference 0 ###LEFT-WALL### 6 found 0 ###LEFT-WALL### 23 . 1 no 4 difference 2 statistically 3 significant 3 significant 4 difference 4 difference 5 was 5 was 6 found 6 found 7 in 6 found 16 in 6 found 20 between 7 in 12 distributions 8 the 12 distributions 9 genotypic 10 and 10 and 11 allelic 10 and 12 distributions 12 distributions 13 of 13 of 15 polymorphisms 14 the 15 polymorphisms 16 in 19 gene 17 the 19 gene 18 xpd 19 gene 20 between 22 groups 21 the 22 groups conclusions : these results suggest that polymorphisms in xrcc1 codon 399 may be associated with the development of age - related cataract [in] han chinese . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 4 results 2 : 5 suggest 2 : 21 related 2 : 26 . 3 these 4 results 4 results 5 suggest 5 suggest 6 that 6 that 7 polymorphisms 6 that 19 age 7 polymorphisms 8 in 8 in 9 xrcc1 9 xrcc1 10 codon 9 xrcc1 18 of 10 codon 11 399 10 codon 12 may 12 may 13 be 13 be 14 associated 14 associated 15 with 15 with 17 development 16 the 17 development 17 development 18 of 20 - 21 related 21 related 25 chinese 22 cataract 25 chinese 24 han 25 chinese atrioventricular ( av ) conduction time ( pr [interval] ) lengthens with age . 0 ###LEFT-WALL### 6 time 0 ###LEFT-WALL### 11 lengthens 0 ###LEFT-WALL### 14 . 1 atrioventricular 3 av 1 atrioventricular 6 time 2 ( 3 av 3 av 4 ) 5 conduction 6 time 6 time 8 pr 6 time 11 lengthens 7 ( 8 pr 8 pr 10 ) 11 lengthens 12 with 12 with 13 age hypertension is often presented as an accelerated aging of the heart and arteries . 0 ###LEFT-WALL### 1 hypertension 0 ###LEFT-WALL### 4 presented 0 ###LEFT-WALL### 14 . 1 hypertension 2 is 2 is 3 often 2 is 4 presented 4 presented 5 as 5 as 8 aging 6 an 8 aging 7 accelerated 8 aging 8 aging 9 of 9 of 12 and 10 the 11 heart 11 heart 12 and 12 and 13 arteries the principal marker of arterial aging is an increase in arterial stiffness and pulse pressure . 0 ###LEFT-WALL### 3 marker 0 ###LEFT-WALL### 7 is 0 ###LEFT-WALL### 16 . 1 the 3 marker 2 principal 3 marker 3 marker 4 of 3 marker 7 is 4 of 6 aging 5 arterial 6 aging 7 is 9 increase 8 an 9 increase 9 increase 10 in 10 in 13 and 11 arterial 12 stiffness 12 stiffness 13 and 13 and 15 pressure 14 pulse 15 pressure we were interested to find out whether parameters of blood pressure and arterial stiffness were related to the pr interval and whether they influenced its long - term progression . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 6 out 0 ###LEFT-WALL### 30 . 1 we 2 were 2 were 3 interested 3 interested 4 to 4 to 6 out 5 find 6 out 6 out 7 whether 7 whether 12 and 7 whether 16 related 8 parameters 9 of 8 parameters 12 and 9 of 11 pressure 10 blood 11 pressure 12 and 14 stiffness 12 and 15 were 13 arterial 14 stiffness 15 were 16 related 16 related 17 to 17 to 21 and 18 the 20 interval 19 pr 20 interval 20 interval 21 and 21 and 22 whether 21 and 23 they 21 and 24 influenced 23 they 24 influenced 24 influenced 29 progression 25 its 29 progression 26 long 27 - 26 long 28 term 28 term 29 progression we examined factors linked to the pr interval at baseline in a cohort of untreated hypertensive patients including office [and] 24 - [hr] blood pressure and arterial stiffness ( qkd ( 100 - 60 ) ) . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 examined 0 ###LEFT-WALL### 37 . 1 we 2 examined 2 examined 3 factors 2 examined 5 to 2 examined 9 at 3 factors 4 linked 5 to 8 interval 6 the 8 interval 7 pr 8 interval 9 at 10 baseline 10 baseline 11 in 10 baseline 14 of 11 in 13 cohort 12 a 13 cohort 14 of 17 patients 15 untreated 17 patients 16 hypertensive 17 patients 17 patients 18 including 17 patients 26 and 18 including 19 office 19 office 21 24 22 - 26 and 24 blood 25 pressure 25 pressure 26 and 26 and 28 stiffness 26 and 30 qkd 26 and 36 ) 27 arterial 28 stiffness 29 ( 30 qkd 30 qkd 33 - 30 qkd 35 ) 31 ( 33 - 32 100 33 - 33 - 34 60 33 - 35 ) long - term evolution of the pr interval and related factors [were] obtained during [follow] - up of this population . 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 21 . 1 long 2 - 1 long 3 term 3 term 4 evolution 4 evolution 5 of 4 evolution 9 and 5 of 8 interval 6 the 8 interval 7 pr 8 interval 9 and 11 factors 9 and 13 obtained 9 and 18 of 10 related 11 factors 13 obtained 14 during 14 during 17 up 16 - 17 up 18 of 20 population 19 this 20 population baseline data were obtained in 1,034 untreated hypertensive patients . 0 ###LEFT-WALL### 2 data 0 ###LEFT-WALL### 4 obtained 0 ###LEFT-WALL### 10 . 1 baseline 2 data 2 data 3 were 3 were 4 obtained 4 obtained 5 in 5 in 9 patients 6 1,034 9 patients 7 untreated 9 patients 8 hypertensive 9 patients at baseline , four variables emerged as significantly and independently correlated with pr [interval] : gender , age , weight , and heart rate . 0 ###LEFT-WALL### 5 variables 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 15 : 0 ###LEFT-WALL### 25 . 1 at 2 baseline 1 at 3 , 1 at 5 variables 4 four 5 variables 5 variables 9 and 6 emerged 8 significantly 6 emerged 9 and 7 as 8 significantly 9 and 11 correlated 10 independently 11 correlated 11 correlated 12 with 12 with 13 pr 15 : 22 and 16 gender 17 , 17 , 18 age 17 , 19 , 19 , 20 weight 19 , 22 and 21 , 22 and 22 and 24 rate 23 heart 24 rate [during] follow - up [(] 137 ± 78 months ) , 328 of these patients were [re] - examined . 0 ###LEFT-WALL### 2 follow 0 ###LEFT-WALL### 11 , 2 follow 4 up 3 - 4 up 4 up 9 months 4 up 10 ) 6 137 9 months 7 ± 9 months 8 78 9 months 11 , 12 328 11 , 16 were 12 328 13 of 12 328 16 were 13 of 15 patients 14 these 15 patients 16 were 19 examined 18 - 19 examined 19 examined 20 . in this group , pr increased from 159 ± 20 to 167 ± 25 [msec] ( p<0.001 ) , a mean alteration of 8 ± [19] msec . 0 ###LEFT-WALL### 5 pr 0 ###LEFT-WALL### 13 ± 1 in 3 group 1 in 4 , 1 in 5 pr 2 this 3 group 5 pr 6 increased 5 pr 13 ± 6 increased 7 from 6 increased 11 to 7 from 9 ± 8 159 9 ± 10 20 11 to 11 to 12 167 13 ± 14 25 14 25 17 p<0.001 14 25 22 alteration 16 ( 17 p<0.001 17 p<0.001 18 ) 19 , 22 alteration 20 a 22 alteration 21 mean 22 alteration 22 alteration 23 of 22 alteration 28 . 23 of 27 msec 24 8 27 msec 25 ± 27 msec this change was correlated with the baseline 24 hr pp [(] r=0.17 , p=0.004 ) and with the duration of [follow] - up ( r=0.13 , p=0.02 ) . 0 ###LEFT-WALL### 2 change 0 ###LEFT-WALL### 4 correlated 0 ###LEFT-WALL### 29 . 1 this 2 change 2 change 3 was 3 was 4 correlated 4 correlated 16 and 5 with 12 r=0.17 5 with 16 and 6 the 12 r=0.17 7 baseline 12 r=0.17 8 24 9 hr 9 hr 12 r=0.17 10 pp 12 r=0.17 12 r=0.17 14 p=0.004 13 , 14 p=0.004 14 p=0.004 15 ) 16 and 17 with 17 with 19 duration 18 the 19 duration 19 duration 20 of 19 duration 27 p=0.02 20 of 23 up 22 - 23 up 24 ( 27 p=0.02 25 r=0.13 26 , 25 r=0.13 27 p=0.02 27 p=0.02 28 ) in the group [with] baseline evaluation of arterial stiffness ( n=141 ) , qkd ( 100 - 60 ) was correlated with the change in pr [interval] ( r= - 0.33 , p<0.0001 ) along with the duration of [follow] - up ( r=0.22 , p=0.005 ) . 0 ###LEFT-WALL### 14 qkd 0 ###LEFT-WALL### 21 correlated 1 in 6 evaluation 1 in 13 , 1 in 14 qkd 2 the 6 evaluation 3 group 6 evaluation 5 baseline 6 evaluation 6 evaluation 7 of 7 of 9 stiffness 8 arterial 9 stiffness 9 stiffness 11 n=141 10 ( 11 n=141 11 n=141 12 ) 14 qkd 17 - 14 qkd 20 was 15 ( 17 - 16 100 17 - 17 - 18 60 17 - 19 ) 20 was 21 correlated 21 correlated 22 with 21 correlated 36 with 22 with 24 change 23 the 24 change 24 change 25 in 25 in 26 pr 26 pr 33 p<0.0001 28 ( 33 p<0.0001 29 r= 31 0.33 29 r= 33 p<0.0001 30 - 31 0.33 31 0.33 32 , 33 p<0.0001 34 ) 35 along 36 with 36 with 38 duration 37 the 38 duration 38 duration 39 of 38 duration 44 r=0.22 39 of 42 up 41 - 42 up 43 ( 44 r=0.22 44 r=0.22 46 p=0.005 44 r=0.22 48 . 45 , 46 p=0.005 46 p=0.005 47 ) this study shows a link between baseline increased pulse pressure or arterial stiffness with the prolongation of the pr interval with aging . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 shows 0 ###LEFT-WALL### 23 . 1 this 2 study 2 study 3 shows 3 shows 5 link 3 shows 10 pressure 3 shows 11 or 3 shows 14 with 3 shows 21 with 4 a 5 link 5 link 6 between 6 between 7 baseline 7 baseline 8 increased 9 pulse 10 pressure 11 or 13 stiffness 12 arterial 13 stiffness 14 with 16 prolongation 15 the 16 prolongation 16 prolongation 17 of 17 of 20 interval 18 the 20 interval 19 pr 20 interval 21 with 22 aging because this link was observed during [follow] - up , it is possible that increased arterial stiffness favors the increase in the pr interval with age . 0 ###LEFT-WALL### 11 it 0 ###LEFT-WALL### 12 is 0 ###LEFT-WALL### 27 . 1 because 3 link 1 because 5 observed 1 because 10 , 1 because 11 it 2 this 3 link 3 link 4 was 4 was 5 observed 5 observed 6 during 6 during 9 up 8 - 9 up 11 it 12 is 12 is 13 possible 13 possible 14 that 14 that 17 stiffness 14 that 18 favors 15 increased 17 stiffness 16 arterial 17 stiffness 17 stiffness 18 favors 18 favors 20 increase 18 favors 21 in 18 favors 25 with 19 the 20 increase 21 in 24 interval 22 the 24 interval 23 pr 24 interval 25 with 26 age [none] the parameters of subjective well [-] being in teachers and their significance in a possible reduction in work capacity and precocious retirement were studied . 0 ###LEFT-WALL### 21 and 0 ###LEFT-WALL### 24 were 0 ###LEFT-WALL### 26 . 2 the 3 parameters 3 parameters 4 of 3 parameters 8 being 3 parameters 11 and 4 of 6 well 5 subjective 6 well 8 being 9 in 9 in 10 teachers 11 and 13 significance 11 and 14 in 11 and 18 in 11 and 21 and 12 their 13 significance 14 in 17 reduction 15 a 16 possible 15 a 17 reduction 16 possible 17 reduction 18 in 20 capacity 19 work 20 capacity 21 and 23 retirement 21 and 24 were 22 precocious 23 retirement 24 were 25 studied the teachers with low need satisfaction levels were found to have increased subjective stress or fatigability on doing their work and decreased rest recovery of work capacity . 0 ###LEFT-WALL### 2 teachers 0 ###LEFT-WALL### 21 and 0 ###LEFT-WALL### 28 . 1 the 2 teachers 2 teachers 3 with 2 teachers 11 have 3 with 6 satisfaction 4 low 5 need 5 need 6 satisfaction 6 satisfaction 7 levels 6 satisfaction 10 to 7 levels 8 were 8 were 9 found 9 found 10 to 11 have 21 and 12 increased 15 or 12 increased 17 on 12 increased 21 and 13 subjective 14 stress 14 stress 15 or 15 or 16 fatigability 17 on 18 doing 18 doing 20 work 19 their 20 work 21 and 22 decreased 22 decreased 24 recovery 23 rest 24 recovery 24 recovery 25 of 25 of 27 capacity 26 work 27 capacity lower need satisfaction levels with negative reasons for refusal to continue work activities appear to be one of the factors of professional aging and its related reduction in their active work period . 0 ###LEFT-WALL### 24 and 0 ###LEFT-WALL### 33 . 1 lower 3 satisfaction 2 need 3 satisfaction 3 satisfaction 4 levels 4 levels 5 with 4 levels 24 and 5 with 7 reasons 6 negative 7 reasons 7 reasons 8 for 7 reasons 13 activities 7 reasons 14 appear 8 for 9 refusal 9 refusal 10 to 9 refusal 11 continue 10 to 11 continue 12 work 13 activities 13 activities 14 appear 14 appear 15 to 14 appear 16 be 15 to 16 be 16 be 17 one 17 one 18 of 17 one 21 of 18 of 20 factors 19 the 20 factors 21 of 23 aging 22 professional 23 aging 24 and 27 reduction 25 its 27 reduction 26 related 27 reduction 27 reduction 28 in 28 in 32 period 29 their 32 period 30 active 31 work 31 work 32 period the availability of an adequate household food supply is critical for the older population . 0 ###LEFT-WALL### 2 availability 0 ###LEFT-WALL### 9 is 0 ###LEFT-WALL### 15 . 1 the 2 availability 2 availability 3 of 2 availability 9 is 3 of 8 supply 4 an 5 adequate 4 an 8 supply 5 adequate 6 household 6 household 8 supply 7 food 8 supply 9 is 10 critical 10 critical 11 for 11 for 14 population 12 the 14 population 13 older 14 population there is little work that has examined food security and the influence [of] nativity on food security among older mexican americans living along the texas - mexico border . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 26 - 0 ###LEFT-WALL### 29 . 1 there 2 is 2 is 4 work 3 little 4 work 4 work 5 that 4 work 7 examined 5 that 6 has 6 has 7 examined 7 examined 10 and 7 examined 15 on 7 examined 18 among 7 examined 23 along 8 food 9 security 9 security 10 and 10 and 14 nativity 11 the 14 nativity 12 influence 14 nativity 15 on 17 security 16 food 17 security 18 among 21 americans 19 older 20 mexican 20 mexican 21 americans 21 americans 22 living 23 along 25 texas 24 the 25 texas 26 - 28 border 27 mexico 28 border using data from 140 older women ( age ≥ 50 [y] ) [who] participated in the 2009 colonia household and community food resource assessment [(] c - hcfra ) , we examined demographic characteristics , health characteristics , food access and mobility , federal and community food and nutrition assistance programs , quality of food environment , food security , eating behaviors , and alternative food sources . 1 using 2 data 2 data 3 from 2 data 9 ≥ 2 data 14 participated 3 from 6 women 4 140 6 women 5 older 6 women 7 ( 9 ≥ 8 age 9 ≥ 9 ≥ 10 50 9 ≥ 12 ) 14 participated 15 in 15 in 20 and 16 the 17 2009 17 2009 19 household 18 colonia 19 household 19 household 20 and 20 and 28 hcfra 20 and 30 , 20 and 31 we 20 and 32 examined 21 community 22 food 22 food 23 resource 23 resource 24 assessment 24 assessment 26 c 24 assessment 28 hcfra 27 - 28 hcfra 28 hcfra 29 ) 31 we 32 examined 32 examined 41 and 33 demographic 34 characteristics 34 characteristics 35 , 35 , 37 characteristics 35 , 38 , 36 health 37 characteristics 38 , 40 access 38 , 41 and 39 food 40 access 41 and 53 quality 42 mobility 43 , 43 , 44 federal 43 , 45 and 45 and 47 food 45 and 48 and 46 community 47 food 48 and 51 programs 48 and 52 , 48 and 53 quality 49 nutrition 51 programs 50 assistance 51 programs 53 quality 54 of 53 quality 61 eating 54 of 56 environment 55 food 56 environment 56 environment 59 security 57 , 59 security 58 food 59 security 59 security 60 , 61 eating 64 and 62 behaviors 64 and 63 , 64 and 64 and 67 sources 64 and 68 . 65 alternative 66 food 66 food 67 sources very low food security was associated with being born in mexico , adjusting for household income and food assistance program participation . 0 ###LEFT-WALL### 3 food 0 ###LEFT-WALL### 6 associated 1 very 2 low 2 low 3 food 3 food 4 security 3 food 5 was 3 food 6 associated 4 security 5 was 6 associated 7 with 7 with 8 being 8 being 9 born 9 born 10 in 9 born 13 adjusting 10 in 11 mexico 12 , 13 adjusting 13 adjusting 14 for 13 adjusting 22 . 14 for 17 and 15 household 16 income 16 income 17 and 17 and 21 participation 18 food 21 participation 19 assistance 21 participation 20 program 21 participation this article provides compelling evidence for enhanced research efforts that will better understand coping strategies and the use of food and nutrition assistance programs for reducing hardship associated with very low food security among older u.s [.] - and mexico - born mexican american women . 0 ###LEFT-WALL### 2 article 0 ###LEFT-WALL### 3 provides 1 this 2 article 2 article 3 provides 3 provides 21 and 4 compelling 5 evidence 5 evidence 6 for 5 evidence 14 coping 5 evidence 16 and 6 for 9 efforts 7 enhanced 8 research 8 research 9 efforts 9 efforts 10 that 9 efforts 13 understand 10 that 11 will 11 will 13 understand 12 better 13 understand 14 coping 15 strategies 16 and 18 use 16 and 19 of 16 and 21 and 17 the 18 use 19 of 20 food 21 and 24 programs 21 and 29 with 22 nutrition 24 programs 23 assistance 24 programs 24 programs 25 for 25 for 26 reducing 26 reducing 27 hardship 27 hardship 28 associated 29 with 39 and 30 very 31 low 31 low 32 food 32 food 33 security 33 security 34 among 33 security 39 and 34 among 36 u.s 35 older 36 u.s 38 - 39 and 39 and 40 mexico 40 mexico 45 women 41 - 45 women 42 born 44 american 43 mexican 44 american 44 american 45 women 45 women 46 . among older adults and seniors , 18.6 % reported food insecurity ( 5.5 [%] [often] and 13.1 % [sometimes] ) , defined as running out of food and not having money to buy more . 0 ###LEFT-WALL### 8 % 0 ###LEFT-WALL### 21 , 0 ###LEFT-WALL### 35 . 1 among 4 and 1 among 6 , 1 among 8 % 2 older 3 adults 3 adults 4 and 4 and 5 seniors 7 18.6 8 % 8 % 21 , 9 reported 11 insecurity 9 reported 21 , 10 food 11 insecurity 11 insecurity 18 % 12 ( 18 % 13 5.5 16 and 16 and 17 13.1 16 and 18 % 18 % 20 ) 21 , 22 defined 22 defined 23 as 22 defined 28 and 22 defined 32 to 22 defined 34 more 23 as 24 running 25 out 26 of 25 out 28 and 26 of 27 food 28 and 29 not 28 and 31 money 30 having 31 money 32 to 33 buy low community social capital was reported by 22.4 % of participants , and 30.8 % indicated they were single , widowed , or divorced [,] an indicator of limited familial social capital . 0 ###LEFT-WALL### 4 capital 0 ###LEFT-WALL### 6 reported 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 33 . 1 low 2 community 2 community 4 capital 3 social 4 capital 4 capital 5 was 5 was 6 reported 6 reported 7 by 7 by 9 % 8 22.4 9 % 9 % 10 of 10 of 11 participants 12 , 13 and 13 and 15 % 13 and 16 indicated 14 30.8 15 % 15 % 16 indicated 16 indicated 17 they 16 indicated 23 or 17 they 23 or 18 were 19 single 18 were 23 or 19 single 21 widowed 20 , 21 widowed 21 widowed 22 , 22 , 23 or 23 or 24 divorced 24 divorced 27 indicator 26 an 27 indicator 27 indicator 28 of 28 of 32 capital 29 limited 31 social 30 familial 31 social 31 social 32 capital a robust multinomial regression model found the odds of reporting greater food insecurity increased for individuals who were women , african american , residents of a household with a low or poverty - level income , individuals who perceived themselves to be worse off than others within their community , and those who had low social capital . 0 ###LEFT-WALL### 42 be 0 ###LEFT-WALL### 45 than 0 ###LEFT-WALL### 58 . 1 a 5 model 2 robust 4 regression 3 multinomial 4 regression 4 regression 5 model 5 model 6 found 6 found 8 odds 6 found 13 insecurity 7 the 8 odds 8 odds 9 of 9 of 10 reporting 10 reporting 12 food 11 greater 12 food 13 insecurity 14 increased 14 increased 15 for 14 increased 41 to 15 for 16 individuals 16 individuals 17 who 16 individuals 18 were 17 who 18 were 18 were 37 individuals 19 women 20 , 20 , 22 american 20 , 23 , 21 african 22 american 23 , 24 residents 23 , 31 or 24 residents 25 of 25 of 27 household 26 a 27 household 27 household 28 with 28 with 30 low 29 a 30 low 31 or 32 poverty 31 or 35 income 31 or 37 individuals 33 - 35 income 34 level 35 income 35 income 36 , 37 individuals 38 who 37 individuals 39 perceived 38 who 39 perceived 39 perceived 40 themselves 41 to 42 be 42 be 44 off 43 worse 44 off 45 than 46 others 45 than 55 low 46 others 47 within 46 others 53 who 46 others 54 had 46 others 55 low 47 within 51 and 48 their 49 community 49 community 51 and 50 , 51 and 51 and 52 those 53 who 54 had 55 low 57 capital 56 social 57 capital compositional level measures of collective social functioning are important associates of food insecurity among older adults and seniors , regardless of severity . 0 ###LEFT-WALL### 3 measures 0 ###LEFT-WALL### 8 are 1 compositional 3 measures 2 level 3 measures 3 measures 4 of 3 measures 8 are 4 of 7 functioning 5 collective 7 functioning 6 social 7 functioning 8 are 10 associates 8 are 14 among 8 are 21 of 9 important 10 associates 10 associates 11 of 11 of 13 insecurity 12 food 13 insecurity 14 among 17 and 15 older 16 adults 16 adults 17 and 17 and 18 seniors 19 , 21 of 20 regardless 21 of 21 of 22 severity 21 of 23 . this study used the concept of material hardship to understand how unmet needs related to food , housing , and health influence depressive symptoms among homebound older adults ( n = 345 ) in north carolina . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 used 0 ###LEFT-WALL### 14 related 0 ###LEFT-WALL### 37 . 1 this 2 study 2 study 3 used 3 used 5 concept 3 used 9 to 3 used 14 related 4 the 5 concept 5 concept 6 of 6 of 8 hardship 7 material 8 hardship 9 to 10 understand 10 understand 11 how 11 how 12 unmet 13 needs 14 related 14 related 15 to 14 related 25 among 14 related 34 in 15 to 20 and 16 food 17 , 17 , 18 housing 17 , 20 and 19 , 20 and 20 and 24 symptoms 21 health 22 influence 22 influence 24 symptoms 23 depressive 24 symptoms 25 among 28 adults 26 homebound 28 adults 27 older 28 adults 28 adults 31 = 29 ( 31 = 30 n 31 = 31 = 32 345 31 = 33 ) 34 in 36 carolina 35 north 36 carolina using data from the nutrition and function study , 37 % reported high levels of depressive symptoms and 17.4 % indicated not receiving needed health care . 0 ###LEFT-WALL### 11 % 0 ###LEFT-WALL### 12 reported 0 ###LEFT-WALL### 18 and 0 ###LEFT-WALL### 27 . 1 using 2 data 1 using 3 from 1 using 9 , 1 using 11 % 3 from 6 and 4 the 5 nutrition 5 nutrition 6 and 6 and 8 study 7 function 8 study 10 37 11 % 11 % 12 reported 12 reported 14 levels 13 high 14 levels 14 levels 15 of 15 of 17 symptoms 16 depressive 17 symptoms 18 and 20 % 18 and 24 needed 19 17.4 20 % 20 % 21 indicated 20 % 22 not 20 % 24 needed 22 not 23 receiving 24 needed 26 care 25 health 26 care approximately 10 % of respondents were food [insecure] ; 30.7 % were at risk for food insecurity ; and 39.7 % reported having to choose between either food and medication or food and paying bills . 0 ###LEFT-WALL### 3 % 0 ###LEFT-WALL### 6 were 0 ###LEFT-WALL### 9 ; 0 ###LEFT-WALL### 36 . 1 approximately 2 10 2 10 3 % 3 % 4 of 3 % 6 were 4 of 5 respondents 6 were 7 food 9 ; 11 % 9 ; 12 were 9 ; 18 ; 10 30.7 11 % 11 % 12 were 12 were 13 at 12 were 15 for 13 at 14 risk 15 for 17 insecurity 16 food 17 insecurity 18 ; 19 and 19 and 21 % 19 and 25 choose 20 39.7 21 % 21 % 22 reported 22 reported 23 having 22 reported 24 to 24 to 25 choose 25 choose 26 between 26 between 33 and 27 either 31 or 28 food 29 and 29 and 30 medication 29 and 31 or 31 or 32 food 31 or 33 and 33 and 35 bills 34 paying 35 bills adjusted logistic regression [model] revealed that food insecurity status ( or [=] 4.9 ) and age 60 - 74 [y] ( or [=] 2.4 ) were significantly associated with a greater number of depressive symptoms . 0 ###LEFT-WALL### 3 regression 0 ###LEFT-WALL### 5 revealed 0 ###LEFT-WALL### 15 and 0 ###LEFT-WALL### 36 . 1 adjusted 3 regression 2 logistic 3 regression 3 regression 5 revealed 5 revealed 9 status 6 that 9 status 7 food 9 status 8 insecurity 9 status 9 status 11 or 10 ( 11 or 11 or 13 4.9 11 or 14 ) 15 and 16 age 15 and 28 associated 16 age 18 - 16 age 22 or 16 age 26 were 17 60 18 - 18 - 19 74 21 ( 22 or 22 or 24 2.4 22 or 25 ) 26 were 27 significantly 26 were 28 associated 28 associated 29 with 29 with 35 symptoms 30 a 32 number 31 greater 32 number 32 number 33 of 32 number 35 symptoms 33 of 35 symptoms 34 depressive 35 symptoms other indicators of material hardship , such as having a major financial difficulty , unmet health need , and inadequate housing , were not significant . 0 ###LEFT-WALL### 2 indicators 0 ###LEFT-WALL### 23 were 0 ###LEFT-WALL### 26 . 1 other 2 indicators 2 indicators 3 of 2 indicators 23 were 3 of 5 hardship 4 material 5 hardship 5 hardship 8 as 6 , 8 as 7 such 8 as 8 as 21 housing 8 as 22 , 9 having 21 housing 10 a 11 major 10 a 13 difficulty 11 major 13 difficulty 12 financial 13 difficulty 13 difficulty 14 , 14 , 17 need 14 , 19 and 15 unmet 17 need 16 health 17 need 18 , 19 and 19 and 20 inadequate 19 and 21 housing 23 were 24 not 23 were 25 significant 24 not 25 significant by far , food insecurity was the most salient influence on depressive symptoms . 0 ###LEFT-WALL### 5 insecurity 0 ###LEFT-WALL### 6 was 0 ###LEFT-WALL### 14 . 1 by 4 food 1 by 5 insecurity 2 far 3 , 2 far 4 food 5 insecurity 6 was 6 was 10 influence 7 the 8 most 8 most 10 influence 9 salient 10 influence 10 influence 11 on 11 on 13 symptoms 12 depressive 13 symptoms these findings have important implications for service providers , researchers , and policymakers . 0 ###LEFT-WALL### 2 findings 0 ###LEFT-WALL### 3 have 0 ###LEFT-WALL### 14 . 1 these 2 findings 2 findings 3 have 3 have 5 implications 4 important 5 implications 5 implications 6 for 6 for 12 and 7 service 8 providers 8 providers 9 , 9 , 10 researchers 9 , 12 and 11 , 12 and 12 and 13 policymakers as a nation , we face a shortage of individuals to serve our aging population . 0 ###LEFT-WALL### 5 we 0 ###LEFT-WALL### 6 face 0 ###LEFT-WALL### 16 . 1 as 3 nation 1 as 4 , 1 as 5 we 2 a 3 nation 5 we 6 face 6 face 8 shortage 6 face 11 to 7 a 8 shortage 8 shortage 9 of 9 of 10 individuals 11 to 12 serve 12 serve 15 population 13 our 15 population 14 aging 15 population therefore , the recruitment of undergraduate students into gerontology programs is an important , [although] challenging task . 0 ###LEFT-WALL### 4 recruitment 0 ###LEFT-WALL### 11 is 0 ###LEFT-WALL### 18 . 1 therefore 2 , 1 therefore 4 recruitment 3 the 4 recruitment 4 recruitment 5 of 4 recruitment 11 is 5 of 7 students 6 undergraduate 7 students 7 students 8 into 8 into 10 programs 9 gerontology 10 programs 11 is 17 task 12 an 13 important 12 an 17 task 13 important 14 , 13 important 17 task 16 challenging 17 task the purpose of this study was to determine if students who do not choose to major in gerontology do so because they simply are unaware of the opportunities or because they are uninterested . 0 ###LEFT-WALL### 8 determine 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 determine 7 to 8 determine 8 determine 9 if 8 determine 34 . 9 if 10 students 9 if 20 so 10 students 11 who 10 students 12 do 10 students 20 so 11 who 12 do 12 do 13 not 12 do 14 choose 14 choose 15 to 14 choose 16 major 15 to 16 major 16 major 17 in 17 in 18 gerontology 19 do 20 so 20 so 21 because 21 because 29 or 21 because 32 are 22 they 24 are 22 they 29 or 23 simply 24 are 24 are 25 unaware 25 unaware 26 of 26 of 28 opportunities 27 the 28 opportunities 29 or 30 because 30 because 31 they 31 they 32 are 32 are 33 uninterested college students who were not gerontology majors ( n = 226 ) were surveyed to determine whether they were aware of a gerontology major at their university , whether they could define gerontology , and their reasons for not pursuing gerontology . 0 ###LEFT-WALL### 2 students 0 ###LEFT-WALL### 16 determine 0 ###LEFT-WALL### 28 , 0 ###LEFT-WALL### 42 . 1 college 2 students 2 students 3 who 2 students 4 were 2 students 10 = 2 students 13 were 3 who 4 were 4 were 5 not 4 were 7 majors 6 gerontology 7 majors 8 ( 10 = 9 n 10 = 10 = 11 226 10 = 12 ) 13 were 14 surveyed 14 surveyed 15 to 15 to 16 determine 16 determine 17 whether 16 determine 25 at 17 whether 18 they 17 whether 19 were 18 they 19 were 19 were 20 aware 20 aware 21 of 21 of 24 major 22 a 23 gerontology 22 a 24 major 23 gerontology 24 major 25 at 27 university 26 their 27 university 28 , 32 define 29 whether 30 they 29 whether 31 could 29 whether 32 define 30 they 31 could 32 define 35 and 33 gerontology 35 and 34 , 35 and 35 and 37 reasons 35 and 38 for 36 their 37 reasons 38 for 39 not 39 not 40 pursuing 40 pursuing 41 gerontology results suggest that a lack of awareness , rather than a lack of interest , may be responsible for the challenges of recruiting college students into the field of gerontology . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 suggest 0 ###LEFT-WALL### 31 . 1 results 2 suggest 2 suggest 3 that 3 that 5 lack 3 that 17 be 4 a 5 lack 5 lack 6 of 5 lack 16 may 6 of 7 awareness 8 , 10 than 9 rather 10 than 10 than 12 lack 10 than 15 , 10 than 16 may 11 a 12 lack 12 lack 13 of 13 of 14 interest 16 may 17 be 17 be 18 responsible 18 responsible 19 for 19 for 21 challenges 20 the 21 challenges 21 challenges 22 of 22 of 23 recruiting 23 recruiting 25 students 23 recruiting 26 into 24 college 25 students 26 into 28 field 27 the 28 field 28 field 29 of 29 of 30 gerontology this implies that the most efficient path to bolstering our gerontology workforce may be to make students aware of the diverse and rewarding career opportunities in the field of aging . 0 ###LEFT-WALL### 1 this 0 ###LEFT-WALL### 16 make 0 ###LEFT-WALL### 31 . 1 this 2 implies 2 implies 3 that 3 that 7 path 3 that 14 be 4 the 7 path 5 most 6 efficient 6 efficient 7 path 7 path 8 to 7 path 13 may 8 to 9 bolstering 9 bolstering 12 workforce 10 our 12 workforce 11 gerontology 12 workforce 13 may 14 be 14 be 15 to 15 to 16 make 16 make 17 students 16 make 18 aware 18 aware 19 of 19 of 22 and 20 the 21 diverse 21 diverse 22 and 22 and 25 opportunities 23 rewarding 24 career 24 career 25 opportunities 25 opportunities 26 in 26 in 28 field 27 the 28 field 28 field 29 of 29 of 30 aging the issues of rising numbers of disasters [,] overwhelming increases in number of older adults , and historically flawed evacuations present real challenges . 0 ###LEFT-WALL### 2 issues 0 ###LEFT-WALL### 21 present 0 ###LEFT-WALL### 24 . 1 the 2 issues 2 issues 3 of 2 issues 9 overwhelming 2 issues 21 present 3 of 7 disasters 4 rising 5 numbers 5 numbers 6 of 5 numbers 7 disasters 6 of 7 disasters 9 overwhelming 10 increases 9 overwhelming 11 in 11 in 17 and 12 number 13 of 12 number 17 and 13 of 15 adults 14 older 15 adults 16 , 17 and 17 and 20 evacuations 18 historically 19 flawed 19 flawed 20 evacuations 21 present 23 challenges 22 real 23 challenges during the next two decades , the number of american baby boomers , who turn 65 , will increase by 40 % . 0 ###LEFT-WALL### 12 boomers 0 ###LEFT-WALL### 19 increase 0 ###LEFT-WALL### 23 . 1 during 5 decades 1 during 6 , 1 during 12 boomers 2 the 3 next 2 the 4 two 4 two 5 decades 7 the 8 number 8 number 9 of 8 number 12 boomers 9 of 12 boomers 10 american 12 boomers 11 baby 12 boomers 12 boomers 14 who 12 boomers 18 will 13 , 14 who 14 who 15 turn 14 who 17 , 15 turn 16 65 18 will 19 increase 19 increase 20 by 20 by 22 % 21 40 22 % as evidenced by recent disasters , the imperfections and vulnerabilities of flawed evacuations for older adults are still present . 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 17 are 0 ###LEFT-WALL### 20 . 1 as 2 evidenced 1 as 9 and 3 by 5 disasters 3 by 6 , 3 by 9 and 4 recent 5 disasters 7 the 8 imperfections 8 imperfections 9 and 9 and 10 vulnerabilities 9 and 11 of 9 and 17 are 11 of 13 evacuations 12 flawed 13 evacuations 13 evacuations 14 for 14 for 16 adults 15 older 16 adults 17 are 18 still 17 are 19 present 18 still 19 present this study examined the level of willingness to evacuate among older adults in the event of a disaster . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 examined 0 ###LEFT-WALL### 19 . 1 this 2 study 2 study 3 examined 3 examined 5 level 4 the 5 level 5 level 6 of 6 of 7 willingness 7 willingness 8 to 7 willingness 9 evacuate 8 to 9 evacuate 9 evacuate 10 among 9 evacuate 13 in 10 among 12 adults 11 older 12 adults 13 in 15 event 14 the 15 event 15 event 16 of 16 of 18 disaster 17 a 18 disaster despite the extensive literature on disasters and evacuation , a significant question regarding evacuation and older adults has not been addressed . 0 ###LEFT-WALL### 12 question 0 ###LEFT-WALL### 21 addressed 0 ###LEFT-WALL### 22 . 1 despite 7 and 1 despite 9 , 1 despite 12 question 2 the 4 literature 3 extensive 4 literature 4 literature 5 on 4 literature 7 and 5 on 6 disasters 7 and 8 evacuation 10 a 12 question 11 significant 12 question 12 question 13 regarding 12 question 18 has 13 regarding 17 adults 14 evacuation 15 and 15 and 16 older 15 and 17 adults 18 has 19 not 18 has 20 been 20 been 21 addressed the study addressed the following concern : what is the level of willingness among older adults to evacuate when asked to do so by emergency management officials ? 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 addressed 0 ###LEFT-WALL### 7 : 0 ###LEFT-WALL### 28 ? 1 the 2 study 2 study 3 addressed 3 addressed 6 concern 4 the 6 concern 5 following 6 concern 7 : 8 what 7 : 23 so 8 what 9 is 8 what 18 evacuate 9 is 11 level 10 the 11 level 11 level 12 of 12 of 13 willingness 13 willingness 14 among 13 willingness 17 to 13 willingness 18 evacuate 14 among 16 adults 15 older 16 adults 17 to 18 evacuate 18 evacuate 19 when 18 evacuate 21 to 19 when 20 asked 21 to 23 so 22 do 23 so 23 so 24 by 24 by 27 officials 25 emergency 26 management 26 management 27 officials the sample population consisted of 765 voluntary participants aged 60 years and older from 30 senior/community centers within seven counties within a midwestern state . 0 ###LEFT-WALL### 3 population 0 ###LEFT-WALL### 4 consisted 0 ###LEFT-WALL### 25 . 1 the 3 population 2 sample 3 population 3 population 4 consisted 4 consisted 5 of 5 of 8 participants 6 765 8 participants 7 voluntary 8 participants 8 participants 16 senior/community 8 participants 17 centers 9 aged 16 senior/community 10 60 11 years 11 years 12 and 12 and 13 older 12 and 16 senior/community 13 older 14 from 14 from 15 30 16 senior/community 17 centers 17 centers 18 within 17 centers 21 within 18 within 20 counties 19 seven 20 counties 21 within 24 state 22 a 24 state 23 midwestern 24 state a group administered survey ( the disaster evacuation survey ) included a total of 15 questions . 0 ###LEFT-WALL### 4 survey 0 ###LEFT-WALL### 11 included 0 ###LEFT-WALL### 17 . 1 a 4 survey 2 group 3 administered 3 administered 4 survey 4 survey 9 survey 4 survey 11 included 5 ( 9 survey 6 the 9 survey 7 disaster 8 evacuation 8 evacuation 9 survey 9 survey 10 ) 11 included 13 total 12 a 13 total 13 total 14 of 14 of 16 questions 15 15 16 questions the findings revealed that older adults are more likely to comply with a mandatory evacuation order . 0 ###LEFT-WALL### 2 findings 0 ###LEFT-WALL### 3 revealed 0 ###LEFT-WALL### 17 . 1 the 2 findings 2 findings 3 revealed 3 revealed 4 that 4 that 6 adults 4 that 7 are 5 older 6 adults 6 adults 7 are 7 are 9 likely 8 more 9 likely 9 likely 10 to 9 likely 11 comply 10 to 11 comply 11 comply 12 with 12 with 16 order 13 a 14 mandatory 13 a 16 order 14 mandatory 15 evacuation 15 evacuation 16 order important practical implications for emergency officials responding to vulnerable older adults in disaster situations are also provided . 0 ###LEFT-WALL### 3 implications 0 ###LEFT-WALL### 17 provided 0 ###LEFT-WALL### 18 . 1 important 3 implications 2 practical 3 implications 3 implications 4 for 3 implications 15 are 4 for 6 officials 5 emergency 6 officials 6 officials 7 responding 7 responding 8 to 7 responding 12 in 8 to 11 adults 9 vulnerable 11 adults 10 older 11 adults 12 in 14 situations 13 disaster 14 situations 15 are 16 also 15 are 17 provided arterial and venous thrombosis have always been regarded as different pathologies and epidemiological studies have examined the association between venous thrombosis and indicators of atherosclerosis [and/or] arterial thromboembolic events . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 7 been 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 30 . 1 arterial 2 and 2 and 4 thrombosis 2 and 5 have 3 venous 4 thrombosis 5 have 7 been 6 always 7 been 7 been 11 pathologies 8 regarded 11 pathologies 9 as 10 different 10 different 11 pathologies 12 and 14 studies 12 and 16 examined 13 epidemiological 14 studies 14 studies 15 have 15 have 16 examined 16 examined 18 association 16 examined 19 between 17 the 18 association 19 between 22 and 20 venous 21 thrombosis 21 thrombosis 22 and 22 and 23 indicators 22 and 24 of 24 of 29 events 25 atherosclerosis 29 events 27 arterial 29 events 28 thromboembolic 29 events we measured the flow - mediated dilation ( fmd ) , a well [-] known marker of arterial endothelial dysfunction , in young - middle [-] aged and old - aged patients [with] and without unprovoked deep venous thrombosis ( dvt ) . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 measured 0 ###LEFT-WALL### 43 . 1 we 2 measured 2 measured 4 flow 2 measured 34 and 3 the 4 flow 4 flow 7 dilation 4 flow 16 marker 5 - 7 dilation 6 mediated 7 dilation 7 dilation 9 fmd 7 dilation 10 ) 8 ( 9 fmd 9 fmd 10 ) 11 , 16 marker 12 a 16 marker 13 well 15 known 15 known 16 marker 16 marker 17 of 16 marker 21 , 17 of 20 dysfunction 18 arterial 20 dysfunction 19 endothelial 20 dysfunction 22 in 32 patients 22 in 34 and 23 young 24 - 23 young 25 middle 25 middle 32 patients 27 aged 28 and 28 and 29 old 28 and 30 - 28 and 31 aged 28 and 32 patients 34 and 35 without 35 without 39 thrombosis 36 unprovoked 39 thrombosis 37 deep 39 thrombosis 38 venous 39 thrombosis 39 thrombosis 41 dvt 40 ( 41 dvt 41 dvt 42 ) the aim of this study was to investigate whether dvt was a significant predictor for impaired fmd , considering all the patients and young - middle - aged ( [age] < 65 years ) and old - aged ( age ≥ 65 years ) patients separately . 0 ###LEFT-WALL### 2 aim 0 ###LEFT-WALL### 16 impaired 1 the 2 aim 2 aim 3 of 2 aim 5 study 2 aim 15 for 2 aim 16 impaired 3 of 4 this 5 study 6 was 6 was 7 to 6 was 8 investigate 7 to 8 investigate 8 investigate 9 whether 8 investigate 15 for 9 whether 10 dvt 9 whether 11 was 10 dvt 11 was 11 was 14 predictor 12 a 14 predictor 13 significant 14 predictor 16 impaired 17 fmd 17 fmd 19 considering 18 , 19 considering 19 considering 20 all 19 considering 46 separately 19 considering 47 . 20 all 21 the 20 all 35 and 21 the 22 patients 22 patients 23 and 23 and 26 middle 23 and 27 - 23 and 28 aged 23 and 33 years 23 and 35 and 24 young 25 - 24 young 26 middle 29 ( 33 years 31 < 32 65 32 65 33 years 33 years 34 ) 35 and 45 patients 36 old 37 - 36 old 45 patients 38 aged 43 years 38 aged 45 patients 39 ( 43 years 40 age 41 ≥ 41 ≥ 43 years 42 65 43 years 43 years 44 ) fmd was measured in the brachial artery on a population of 120 subjects with the same atherosclerosis risk factors , 68 male and 52 female , 70 young - middle - aged subjects ( mean age ± sd 49.5 ± 10.5 years [ )(and 50 old - aged subjects ( 76.2 ± 7.7 years ) . 0 ###LEFT-WALL### 1 fmd 0 ###LEFT-WALL### 20 , 1 fmd 2 was 2 was 3 measured 3 measured 4 in 3 measured 8 on 4 in 7 artery 5 the 7 artery 6 brachial 7 artery 8 on 10 population 9 a 10 population 10 population 11 of 10 population 18 risk 10 population 19 factors 11 of 13 subjects 12 120 13 subjects 13 subjects 14 with 14 with 16 same 15 the 16 same 17 atherosclerosis 18 risk 18 risk 19 factors 20 , 30 middle 20 , 31 - 21 68 30 middle 22 male 23 and 23 and 25 female 23 and 26 , 23 and 30 middle 24 52 25 female 27 70 30 middle 28 young 29 - 28 young 30 middle 31 - 33 subjects 31 - 48 aged 31 - 56 . 32 aged 33 subjects 33 subjects 44 )(and 33 subjects 48 aged 34 ( 44 )(and 35 mean 42 years 36 age 37 ± 37 ± 42 years 38 sd 42 years 39 49.5 42 years 40 ± 42 years 41 10.5 42 years 42 years 44 )(and 44 )(and 46 old 44 )(and 47 - 45 50 46 old 48 aged 49 subjects 49 subjects 54 years 50 ( 54 years 51 76.2 54 years 52 ± 54 years 53 7.7 54 years 54 years 55 ) patients with dvt showed a significant decrease of fmd compared to patients without dvt [(] 6.8 ± 5.5 % [vs] . 10.9 ± 3.5 % , p < 0.001 ) . 0 ###LEFT-WALL### 1 patients 0 ###LEFT-WALL### 4 showed 0 ###LEFT-WALL### 21 . 1 patients 2 with 1 patients 4 showed 2 with 3 dvt 4 showed 7 decrease 4 showed 11 to 4 showed 16 6.8 4 showed 17 ± 5 a 7 decrease 6 significant 7 decrease 7 decrease 8 of 8 of 9 fmd 9 fmd 10 compared 11 to 12 patients 13 without 14 dvt 13 without 16 6.8 16 6.8 17 ± 17 ± 19 % 18 5.5 19 % 21 . 22 10.9 21 . 23 ± 21 . 31 . 22 10.9 23 ± 23 ± 25 % 24 3.5 25 % 25 % 28 < 26 , 28 < 27 p 28 < 28 < 29 0.001 28 < 30 ) moreover , old - aged patients showed a significant decrease of fmd compared to the young - middle - aged subjects [(] 7.4 ± 4.1 % [vs] . 9.8 ± 5.3 % , p = 0.005 ) . 0 ###LEFT-WALL### 6 patients 0 ###LEFT-WALL### 7 showed 0 ###LEFT-WALL### 28 . 1 moreover 2 , 1 moreover 6 patients 3 old 4 - 3 old 6 patients 5 aged 6 patients 6 patients 7 showed 7 showed 10 decrease 7 showed 21 subjects 7 showed 24 ± 8 a 9 significant 8 a 10 decrease 9 significant 10 decrease 10 decrease 11 of 11 of 12 fmd 12 fmd 13 compared 13 compared 14 to 13 compared 19 - 13 compared 20 aged 14 to 18 middle 15 the 18 middle 16 young 17 - 16 young 18 middle 21 subjects 23 7.4 21 subjects 24 ± 24 ± 26 % 25 4.1 26 % 28 . 29 9.8 28 . 30 ± 28 . 38 . 29 9.8 30 ± 30 ± 32 % 31 5.3 32 % 32 % 35 = 33 , 35 = 34 p 35 = 35 = 36 0.005 35 = 37 ) in the whole study population , dvt was strongly associated with fmd ( risk factors adjusted β = - 4.14 , p < 0.001 ) . 0 ###LEFT-WALL### 7 dvt 0 ###LEFT-WALL### 10 associated 0 ###LEFT-WALL### 26 . 1 in 5 population 1 in 6 , 1 in 7 dvt 2 the 5 population 3 whole 4 study 4 study 5 population 7 dvt 8 was 8 was 9 strongly 8 was 10 associated 10 associated 11 with 10 associated 23 < 11 with 12 fmd 12 fmd 15 factors 13 ( 15 factors 14 risk 15 factors 15 factors 17 β 15 factors 18 = 15 factors 19 - 16 adjusted 17 β 17 β 18 = 20 4.14 23 < 21 , 23 < 22 p 23 < 23 < 24 0.001 23 < 25 ) a significant interaction between age and the presence of dvt on predicting fmd was found ( p = 0.003 ) suggesting a differential behavior of dvt as [predictor] of fmd . 0 ###LEFT-WALL### 6 and 0 ###LEFT-WALL### 31 . 1 a 2 significant 1 a 3 interaction 2 significant 3 interaction 3 interaction 4 between 3 interaction 6 and 4 between 5 age 6 and 8 presence 6 and 9 of 7 the 8 presence 9 of 10 dvt 10 dvt 11 on 10 dvt 21 suggesting 11 on 12 predicting 12 predicting 13 fmd 12 predicting 15 found 13 fmd 14 was 14 was 15 found 15 found 18 = 16 ( 18 = 17 p 18 = 18 = 19 0.003 18 = 20 ) 21 suggesting 24 behavior 21 suggesting 27 as 22 a 24 behavior 23 differential 24 behavior 24 behavior 25 of 25 of 26 dvt 27 as 29 of 29 of 30 fmd in young - middle - aged group , multivariate [model] confirmed that dvt was the most significant predictor of continuous fmd ( β [=] - 6.06 , p < 0.001 ) . 0 ###LEFT-WALL### 4 middle 0 ###LEFT-WALL### 5 - 0 ###LEFT-WALL### 32 . 1 in 4 middle 2 young 3 - 2 young 4 middle 5 - 7 group 5 - 8 , 5 - 25 - 6 aged 7 group 8 , 9 multivariate 8 , 11 confirmed 9 multivariate 11 confirmed 11 confirmed 12 that 12 that 13 dvt 12 that 14 was 13 dvt 14 was 14 was 18 predictor 15 the 18 predictor 16 most 17 significant 17 significant 18 predictor 18 predictor 19 of 18 predictor 23 β 19 of 21 fmd 20 continuous 21 fmd 22 ( 23 β 23 β 25 - 25 - 26 6.06 26 6.06 29 < 27 , 29 < 28 p 29 < 29 < 30 0.001 29 < 31 ) on the contrary , dvt was no more a predictor of fmd in the old age group ( β [=] - 0.73 , p = 0.556 ) . 0 ###LEFT-WALL### 5 dvt 0 ###LEFT-WALL### 6 was 0 ###LEFT-WALL### 28 . 1 on 3 contrary 1 on 4 , 1 on 5 dvt 2 the 3 contrary 5 dvt 6 was 6 was 8 more 6 was 10 predictor 6 was 13 in 6 was 25 = 7 no 8 more 9 a 10 predictor 10 predictor 11 of 11 of 12 fmd 13 in 17 group 14 the 17 group 15 old 17 group 16 age 17 group 17 group 19 β 18 ( 19 β 19 β 21 - 22 0.73 25 = 23 , 25 = 24 p 25 = 25 = 26 0.556 25 = 27 ) furthermore , old - aged patients without dvt showed a statistically significant decrease of fmd compared to the young - middle - aged subjects without dvt [(] 8.2 ± 2.1 [%] vs [.] 12.6 ± 2.7 [%] , p<0.001 [ )(and old - aged patients with dvt showed a [not] statistically significant decrease of the fmd compared to the young - middle - aged patients with dvt ( 6.7 ± 5.3 % [vs] [.] 6.8 ± 5.7 [%] , p = 0.932 ) . 0 ###LEFT-WALL### 6 patients 0 ###LEFT-WALL### 9 showed 1 furthermore 6 patients 2 , 3 old 3 old 4 - 3 old 6 patients 5 aged 6 patients 6 patients 7 without 6 patients 9 showed 7 without 8 dvt 9 showed 13 decrease 9 showed 16 compared 10 a 11 statistically 10 a 13 decrease 11 statistically 12 significant 12 significant 13 decrease 13 decrease 14 of 13 decrease 16 compared 14 of 15 fmd 16 compared 17 to 16 compared 22 - 17 to 19 young 18 the 19 young 20 - 22 - 21 middle 22 - 22 - 24 subjects 23 aged 24 subjects 24 subjects 25 without 24 subjects 32 vs 25 without 29 ± 26 dvt 28 8.2 26 dvt 29 ± 29 ± 30 2.1 32 vs 41 )(and 34 12.6 35 ± 35 ± 36 2.7 35 ± 38 , 38 , 39 p<0.001 38 , 41 )(and 41 )(and 42 old 41 )(and 43 - 41 )(and 45 patients 41 )(and 48 showed 44 aged 45 patients 45 patients 46 with 45 patients 48 showed 46 with 47 dvt 48 showed 53 decrease 48 showed 58 to 49 a 53 decrease 51 statistically 52 significant 52 significant 53 decrease 53 decrease 54 of 54 of 56 fmd 55 the 56 fmd 56 fmd 57 compared 58 to 65 patients 59 the 65 patients 60 young 62 middle 60 young 63 - 60 young 65 patients 61 - 62 middle 62 middle 63 - 64 aged 65 patients 65 patients 66 with 66 with 67 dvt 67 dvt 76 ± 68 ( 76 ± 69 6.7 76 ± 70 ± 76 ± 71 5.3 72 % 72 % 76 ± 75 6.8 76 ± 76 ± 81 = 76 ± 84 . 77 5.7 81 = 79 , 81 = 80 p 81 = 81 = 82 0.932 81 = 83 ) in conclusion , young - middle - aged patients with spontaneous dvt show an impaired fmd , whereas this impairment in old - aged subjects is evident independently from the presence or absence of dvt . 0 ###LEFT-WALL### 2 conclusion 0 ###LEFT-WALL### 3 , 0 ###LEFT-WALL### 26 is 0 ###LEFT-WALL### 36 . 1 in 2 conclusion 3 , 6 middle 3 , 7 - 4 young 5 - 4 young 6 middle 7 - 9 patients 7 - 13 show 8 aged 9 patients 9 patients 10 with 9 patients 13 show 10 with 12 dvt 11 spontaneous 12 dvt 13 show 16 fmd 13 show 18 whereas 14 an 16 fmd 15 impaired 16 fmd 17 , 18 whereas 18 whereas 20 impairment 19 this 20 impairment 20 impairment 21 in 20 impairment 26 is 21 in 25 subjects 22 old 23 - 22 old 25 subjects 24 aged 25 subjects 26 is 27 evident 27 evident 28 independently 28 independently 29 from 29 from 32 or 30 the 31 presence 31 presence 32 or 32 or 33 absence 32 or 34 of 34 of 35 dvt aging per se may be associated with physiologic abnormalities in the systemic arteries and with endothelial dysfunction . 0 ###LEFT-WALL### 1 aging 0 ###LEFT-WALL### 6 associated 0 ###LEFT-WALL### 18 . 1 aging 4 may 2 per 3 se 3 se 4 may 4 may 5 be 5 be 6 associated 6 associated 7 with 7 with 9 abnormalities 8 physiologic 9 abnormalities 9 abnormalities 14 and 10 in 13 arteries 10 in 14 and 11 the 13 arteries 12 systemic 13 arteries 14 and 15 with 15 with 17 dysfunction 16 endothelial 17 dysfunction the pathological processes of neurodegenerative disorders such as alzheimer 's and parkinson 's diseases engender synaptic and neuronal cell damage . 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 15 engender 0 ###LEFT-WALL### 21 . 1 the 3 processes 2 pathological 3 processes 3 processes 4 of 3 processes 11 and 4 of 6 disorders 5 neurodegenerative 6 disorders 6 disorders 8 as 7 such 8 as 8 as 10 's 9 alzheimer 10 's 11 and 14 diseases 11 and 15 engender 12 parkinson 13 's 13 's 14 diseases 15 engender 20 damage 16 synaptic 17 and 17 and 18 neuronal 17 and 19 cell 19 cell 20 damage while mild oxidative and nitrosative ( nitric oxide ( no ) - related ) stress mediates normal neuronal signaling , excessive accumulation of these free radicals is linked to neuronal cell injury or death . 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 13 related 0 ###LEFT-WALL### 20 , 0 ###LEFT-WALL### 35 . 1 while 2 mild 1 while 4 and 3 oxidative 4 and 4 and 5 nitrosative 4 and 8 oxide 4 and 13 related 6 ( 8 oxide 7 nitric 8 oxide 8 oxide 10 no 8 oxide 12 - 9 ( 10 no 10 no 11 ) 13 related 14 ) 13 related 15 stress 13 related 16 mediates 15 stress 16 mediates 16 mediates 19 signaling 17 normal 19 signaling 18 neuronal 19 signaling 20 , 22 accumulation 20 , 28 linked 21 excessive 22 accumulation 22 accumulation 23 of 22 accumulation 27 is 23 of 26 radicals 24 these 26 radicals 25 free 26 radicals 27 is 28 linked 28 linked 29 to 29 to 33 or 30 neuronal 31 cell 31 cell 32 injury 32 injury 33 or 33 or 34 death in neurons , n - methyl - d - aspartate ( nmda ) [receptor] ( nmdar ) activation and subsequent ca ( 2+ ) influx can induce the generation of no via neuronal no synthase . 0 ###LEFT-WALL### 19 and 0 ###LEFT-WALL### 27 induce 0 ###LEFT-WALL### 36 . 1 in 2 neurons 1 in 19 and 2 neurons 4 n 2 neurons 6 methyl 2 neurons 9 - 3 , 4 n 4 n 5 - 5 - 6 methyl 6 methyl 7 - 7 - 9 - 8 d 9 - 9 - 10 aspartate 9 - 17 ) 10 aspartate 12 nmda 10 aspartate 16 nmdar 11 ( 12 nmda 12 nmda 13 ) 15 ( 16 nmdar 16 nmdar 17 ) 18 activation 19 and 19 and 26 can 19 and 27 induce 20 subsequent 26 can 21 ca 23 2+ 21 ca 26 can 22 ( 23 2+ 23 2+ 24 ) 25 influx 26 can 27 induce 29 generation 27 induce 32 via 28 the 29 generation 29 generation 30 of 30 of 31 no 32 via 35 synthase 33 neuronal 35 synthase 34 no 35 synthase emerging evidence has demonstrated [that] s - nitrosylation , representing covalent reaction of an no group with a critical protein thiol , mediates the vast majority of no signaling . 0 ###LEFT-WALL### 2 evidence 0 ###LEFT-WALL### 4 demonstrated 0 ###LEFT-WALL### 7 - 0 ###LEFT-WALL### 30 . 1 emerging 2 evidence 2 evidence 3 has 3 has 4 demonstrated 4 demonstrated 6 s 7 - 8 nitrosylation 7 - 23 mediates 8 nitrosylation 10 representing 8 nitrosylation 23 mediates 9 , 10 representing 10 representing 12 reaction 10 representing 22 , 11 covalent 12 reaction 12 reaction 13 of 13 of 16 group 14 an 16 group 15 no 16 group 16 group 17 with 17 with 21 thiol 18 a 21 thiol 19 critical 20 protein 20 protein 21 thiol 23 mediates 28 no 24 the 26 majority 25 vast 26 majority 26 majority 27 of 26 majority 28 no 27 of 28 no 28 no 29 signaling analogous to phosphorylation and other posttranslational modifications , s - nitrosylation can regulate the biological activity of many proteins . 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 8 , 0 ###LEFT-WALL### 20 . 1 analogous 2 to 1 analogous 4 and 2 to 3 phosphorylation 4 and 7 modifications 5 other 7 modifications 6 posttranslational 7 modifications 8 , 9 s 8 , 10 - 9 s 10 - 10 - 11 nitrosylation 11 nitrosylation 12 can 12 can 13 regulate 13 regulate 16 activity 14 the 16 activity 15 biological 16 activity 16 activity 17 of 17 of 19 proteins 18 many 19 proteins here , we discuss recent studies that implicate neuropathogenic roles of s - nitrosylation in protein misfolding , mitochondrial dysfunction , synaptic injury , and eventual neuronal loss . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 discuss 0 ###LEFT-WALL### 18 , 0 ###LEFT-WALL### 29 . 1 here 2 , 1 here 3 we 3 we 4 discuss 4 discuss 6 studies 5 recent 6 studies 6 studies 7 that 6 studies 8 implicate 7 that 8 implicate 8 implicate 10 roles 9 neuropathogenic 10 roles 10 roles 11 of 10 roles 14 nitrosylation 11 of 12 s 13 - 14 nitrosylation 14 nitrosylation 15 in 14 nitrosylation 18 , 15 in 16 protein 16 protein 17 misfolding 18 , 25 and 19 mitochondrial 20 dysfunction 20 dysfunction 21 , 21 , 23 injury 21 , 25 and 22 synaptic 23 injury 24 , 25 and 25 and 28 loss 26 eventual 28 loss 27 neuronal 28 loss among a growing number of s - nitrosylated proteins that contribute to disease pathogenesis , in this review we focus on s - nitrosylated protein - disulfide isomerase ( forming sno - pdi ) and dynamin - related protein 1 ( forming sno - drp1 ) . 0 ###LEFT-WALL### 19 we 0 ###LEFT-WALL### 20 focus 0 ###LEFT-WALL### 38 related 1 among 4 number 1 among 15 , 1 among 19 we 2 a 4 number 3 growing 4 number 4 number 5 of 4 number 9 proteins 5 of 6 s 7 - 9 proteins 8 nitrosylated 9 proteins 9 proteins 10 that 9 proteins 11 contribute 9 proteins 15 , 10 that 11 contribute 11 contribute 12 to 12 to 14 pathogenesis 13 disease 14 pathogenesis 16 in 18 review 16 in 19 we 17 this 18 review 19 we 20 focus 20 focus 21 on 20 focus 26 - 21 on 22 s 23 - 26 - 24 nitrosylated 25 protein 25 protein 26 - 26 - 28 isomerase 26 - 37 - 27 disulfide 28 isomerase 28 isomerase 30 forming 29 ( 30 forming 30 forming 35 and 30 forming 37 - 31 sno 33 pdi 31 sno 35 and 32 - 33 pdi 33 pdi 34 ) 35 and 36 dynamin 37 - 38 related 38 related 39 protein 38 related 42 forming 38 related 47 . 39 protein 40 1 41 ( 42 forming 42 forming 43 sno 42 forming 46 ) 43 sno 45 drp1 44 - 45 drp1 45 drp1 46 ) furthermore , we describe drugs , such as memantine and newer derivatives of this compound that can prevent both hyperactivation of extrasynaptic nmdars as well as downstream pathways that lead to nitrosative stress , synaptic damage , and neuronal loss . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 describe 0 ###LEFT-WALL### 34 , 0 ###LEFT-WALL### 41 . 1 furthermore 2 , 1 furthermore 3 we 3 we 4 describe 4 describe 5 drugs 4 describe 8 as 6 , 8 as 7 such 8 as 8 as 20 hyperactivation 8 as 34 , 9 memantine 10 and 10 and 12 derivatives 10 and 13 of 10 and 20 hyperactivation 11 newer 12 derivatives 13 of 15 compound 14 this 15 compound 15 compound 16 that 15 compound 17 can 16 that 17 can 17 can 18 prevent 18 prevent 19 both 20 hyperactivation 21 of 20 hyperactivation 26 as 21 of 23 nmdars 22 extrasynaptic 23 nmdars 24 as 25 well 25 well 26 as 26 as 28 pathways 27 downstream 28 pathways 28 pathways 29 that 28 pathways 30 lead 29 that 30 lead 30 lead 31 to 31 to 33 stress 32 nitrosative 33 stress 34 , 38 and 35 synaptic 36 damage 36 damage 38 and 37 , 38 and 38 and 40 loss 39 neuronal 40 loss background : the estimated life expectancy of older persons is an important component [of] medical decision - making . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 6 expectancy 2 : 10 is 3 the 6 expectancy 4 estimated 5 life 5 life 6 expectancy 6 expectancy 7 of 6 expectancy 10 is 7 of 9 persons 8 older 9 persons 10 is 16 decision 11 an 12 important 11 an 16 decision 12 important 16 decision 13 component 16 decision 15 medical 16 decision 16 decision 18 making 17 - 18 making 18 making 19 . to date , no data are available on the accuracy of health care professionals in estimating the remaining life expectancy of older subjects . 0 ###LEFT-WALL### 1 to 0 ###LEFT-WALL### 2 date 0 ###LEFT-WALL### 3 , 0 ###LEFT-WALL### 24 . 1 to 2 date 3 , 5 data 3 , 6 are 4 no 5 data 5 data 6 are 6 are 7 available 7 available 8 on 7 available 15 in 8 on 10 accuracy 9 the 10 accuracy 10 accuracy 11 of 11 of 14 professionals 12 health 14 professionals 13 care 14 professionals 15 in 16 estimating 16 estimating 20 expectancy 17 the 18 remaining 17 the 20 expectancy 19 life 20 expectancy 20 expectancy 21 of 21 of 23 subjects 22 older 23 subjects methods : a survey estimating the mean remaining life expectancy of germans of both sexes at the ages of 0 , 70 , 80 and 90 years was performed from september to november 2010 . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 4 survey 2 : 29 performed 2 : 35 . 3 a 4 survey 4 survey 5 estimating 4 survey 28 was 5 estimating 10 expectancy 5 estimating 15 sexes 6 the 10 expectancy 7 mean 10 expectancy 8 remaining 10 expectancy 9 life 10 expectancy 10 expectancy 11 of 10 expectancy 13 of 10 expectancy 15 sexes 11 of 12 germans 13 of 14 both 15 sexes 16 at 15 sexes 27 years 16 at 18 ages 17 the 18 ages 18 ages 19 of 18 ages 22 70 19 of 20 0 21 , 22 70 22 70 23 , 24 80 25 and 25 and 26 90 25 and 27 years 28 was 29 performed 29 performed 30 from 29 performed 32 to 30 from 31 september 32 to 33 november 33 november 34 2010 results : two hundred and six health care professionals underestimated the mean remaining life expectancy of older persons by 10 % , on average , and with great variance ( [sd] = 34 % ) . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 36 . 2 : 9 professionals 2 : 10 underestimated 3 two 4 hundred 4 hundred 5 and 5 and 6 six 6 six 9 professionals 7 health 9 professionals 8 care 9 professionals 9 professionals 10 underestimated 10 underestimated 12 mean 11 the 12 mean 12 mean 13 remaining 12 mean 16 of 13 remaining 15 expectancy 14 life 15 expectancy 16 of 18 persons 17 older 18 persons 18 persons 26 and 19 by 21 % 19 by 26 and 20 10 21 % 21 % 24 average 22 , 24 average 23 on 24 average 24 average 25 , 25 , 26 and 26 and 27 with 27 with 29 variance 28 great 29 variance 29 variance 34 % 30 ( 34 % 32 = 33 34 33 34 34 % 34 % 35 ) medical doctors , especially those [not] specialized in geriatrics , estimated [worst] . 0 ###LEFT-WALL### 2 doctors 0 ###LEFT-WALL### 3 , 0 ###LEFT-WALL### 13 . 1 medical 2 doctors 3 , 5 those 3 , 7 specialized 4 especially 5 those 5 those 7 specialized 7 specialized 8 in 8 in 10 , 9 geriatrics 10 , 10 , 11 estimated conclusions : underestimation of the remaining life expectancy of older people is prevalent in health care professionals and may lead to patients being managed inappropriately . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 26 . 2 : 3 underestimation 2 : 18 and 3 underestimation 4 of 3 underestimation 18 and 4 of 8 expectancy 5 the 6 remaining 5 the 8 expectancy 7 life 8 expectancy 8 expectancy 9 of 9 of 11 people 10 older 11 people 12 is 13 prevalent 12 is 18 and 13 prevalent 14 in 14 in 17 professionals 15 health 16 care 16 care 17 professionals 18 and 19 may 18 and 25 inappropriately 19 may 20 lead 20 lead 21 to 21 to 22 patients 22 patients 23 being 23 being 24 managed this underscores the need for further studies and better training on this issue in health care education . 0 ###LEFT-WALL### 1 this 0 ###LEFT-WALL### 2 underscores 0 ###LEFT-WALL### 18 . 1 this 2 underscores 2 underscores 4 need 2 underscores 5 for 2 underscores 11 on 2 underscores 14 in 3 the 4 need 5 for 8 and 6 further 7 studies 7 studies 8 and 8 and 10 training 9 better 10 training 11 on 13 issue 12 this 13 issue 14 in 17 education 15 health 16 care 16 care 17 education osteoporosis is a common disorder in aging populations that imposes considerable health problems . 0 ###LEFT-WALL### 1 osteoporosis 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 14 . 1 osteoporosis 2 is 2 is 5 disorder 3 a 4 common 3 a 5 disorder 4 common 5 disorder 5 disorder 6 in 5 disorder 9 that 5 disorder 10 imposes 6 in 7 aging 7 aging 8 populations 9 that 10 imposes 10 imposes 13 problems 11 considerable 12 health 12 health 13 problems tartrate - resistant acid phosphatase type 5b ( trap - 5b ) is derived from osteoclasts , and is involved in normal bone homeostasis . 0 ###LEFT-WALL### 1 tartrate 0 ###LEFT-WALL### 18 and 0 ###LEFT-WALL### 25 . 1 tartrate 7 5b 1 tartrate 18 and 2 - 7 5b 3 resistant 4 acid 4 acid 7 5b 5 phosphatase 6 type 6 type 7 5b 7 5b 9 trap 7 5b 11 5b 7 5b 12 ) 8 ( 9 trap 9 trap 10 - 10 - 11 5b 11 5b 12 ) 13 is 14 derived 13 is 18 and 14 derived 15 from 15 from 16 osteoclasts 17 , 18 and 18 and 19 is 19 is 20 involved 20 involved 21 in 21 in 24 homeostasis 22 normal 23 bone 23 bone 24 homeostasis recently , a novel assay system for trap - 5b , the fragments absorbed immunocapture enzymatic assay method , has been developed . 0 ###LEFT-WALL### 6 system 0 ###LEFT-WALL### 22 developed 0 ###LEFT-WALL### 23 . 1 recently 2 , 1 recently 6 system 3 a 4 novel 3 a 6 system 4 novel 5 assay 5 assay 6 system 6 system 7 for 6 system 10 5b 6 system 18 method 6 system 20 has 7 for 8 trap 9 - 10 5b 10 5b 11 , 11 , 18 method 12 the 18 method 13 fragments 14 absorbed 14 absorbed 15 immunocapture 15 immunocapture 18 method 16 enzymatic 17 assay 17 assay 18 method 18 method 19 , 20 has 21 been 21 been 22 developed to evaluate the suitability of trap - 5b as a screening marker for bone mineral density ( bmd ) , [we] explored [the] correlations between serum trap - 5b concentrations and laboratory findings , body mass index , [or] bmd in 462 community - dwelling elderly individuals ( 249 men and 213 women , age 73.4±6.5 years [ )(who participated in a regular medical screening program . 0 ###LEFT-WALL### 1 to 0 ###LEFT-WALL### 2 evaluate 0 ###LEFT-WALL### 7 - 0 ###LEFT-WALL### 8 5b 1 to 2 evaluate 2 evaluate 4 suitability 3 the 4 suitability 4 suitability 5 of 5 of 6 trap 7 - 8 5b 8 5b 9 as 9 as 12 marker 10 a 12 marker 11 screening 12 marker 12 marker 13 for 13 for 16 density 14 bone 15 mineral 15 mineral 16 density 16 density 18 bmd 16 density 28 - 17 ( 18 bmd 18 bmd 19 ) 20 , 28 - 22 explored 24 correlations 24 correlations 25 between 24 correlations 28 - 25 between 27 trap 26 serum 27 trap 28 - 37 index 29 5b 35 body 30 concentrations 31 and 31 and 33 findings 31 and 34 , 31 and 35 body 32 laboratory 33 findings 35 body 37 index 36 mass 37 index 37 index 40 bmd 37 index 45 dwelling 38 , 40 bmd 40 bmd 41 in 40 bmd 44 - 41 in 43 community 42 462 43 community 44 - 45 dwelling 45 dwelling 47 individuals 46 elderly 47 individuals 47 individuals 51 and 47 individuals 57 years 48 ( 51 and 49 249 50 men 50 men 51 and 51 and 53 women 51 and 54 , 52 213 53 women 54 , 57 years 55 age 56 73.4±6.5 56 73.4±6.5 57 years 57 years 59 )(who 57 years 60 participated 57 years 67 . 59 )(who 60 participated 60 participated 61 in 61 in 66 program 62 a 66 program 63 regular 66 program 64 medical 66 program 65 screening 66 program in conclusion , the elevated serum level of trap [-] 5b is independently correlated with the decreased bmd in women , but not in men . 0 ###LEFT-WALL### 2 conclusion 0 ###LEFT-WALL### 3 , 0 ###LEFT-WALL### 26 . 1 in 2 conclusion 3 , 7 level 3 , 14 correlated 4 the 7 level 5 elevated 6 serum 6 serum 7 level 7 level 8 of 7 level 12 is 8 of 11 5b 9 trap 11 5b 12 is 13 independently 12 is 14 correlated 14 correlated 15 with 14 correlated 22 but 15 with 18 bmd 16 the 18 bmd 17 decreased 18 bmd 19 in 20 women 19 in 22 but 21 , 22 but 22 but 23 not 22 but 24 in 24 in 25 men because measurement of trap - 5b is not affected by food intake , and blood samples can be collected at any time of the day , we suggest the suitability of serum trap - 5b as a simple marker for the evaluation of bmd in women . 0 ###LEFT-WALL### 27 we 0 ###LEFT-WALL### 28 suggest 1 because 14 and 1 because 18 be 1 because 26 , 1 because 27 we 2 measurement 3 of 2 measurement 10 by 2 measurement 14 and 3 of 4 trap 4 trap 9 affected 5 - 9 affected 6 5b 7 is 7 is 8 not 8 not 9 affected 10 by 12 intake 11 food 12 intake 13 , 14 and 14 and 17 can 14 and 18 be 15 blood 17 can 16 samples 17 can 18 be 19 collected 19 collected 20 at 20 at 22 time 21 any 22 time 22 time 23 of 23 of 25 day 24 the 25 day 27 we 28 suggest 28 suggest 30 suitability 29 the 30 suitability 30 suitability 31 of 30 suitability 35 5b 31 of 33 trap 32 serum 33 trap 34 - 35 5b 35 5b 36 as 35 5b 47 . 36 as 39 marker 37 a 38 simple 37 a 39 marker 38 simple 39 marker 39 marker 40 for 40 for 42 evaluation 41 the 42 evaluation 42 evaluation 43 of 43 of 44 bmd 44 bmd 45 in 45 in 46 women yttria - based zirconia material ( y - tzp ) widely used in dentistry , may degrade [in] a humid , low - temperature environment such as that in the oral cavity . 0 ###LEFT-WALL### 1 yttria 0 ###LEFT-WALL### 17 degrade 0 ###LEFT-WALL### 33 . 1 yttria 4 zirconia 1 yttria 16 may 2 - 4 zirconia 3 based 4 zirconia 4 zirconia 5 material 4 zirconia 12 used 4 zirconia 15 , 5 material 7 y 5 material 9 tzp 5 material 12 used 6 ( 7 y 7 y 8 - 8 - 9 tzp 9 tzp 10 ) 11 widely 12 used 12 used 13 in 13 in 14 dentistry 16 may 17 degrade 17 degrade 25 environment 17 degrade 29 in 19 a 20 humid 19 a 25 environment 20 humid 21 , 20 humid 24 temperature 22 low 23 - 22 low 24 temperature 24 temperature 25 environment 25 environment 27 as 26 such 27 as 27 as 28 that 29 in 32 cavity 30 the 32 cavity 31 oral 32 cavity the aim of this study was to compare the degradation of a new silica doped y [-] tzp material with that of conventional [y] - tzp by using accelerated aging tests at 200 °c [.] the results of the accelerated tests revealed that after 50 hours of aging , the conventional [y] - tzp samples had damaged surfaces that were weakened by 50 to 60 % , [while] the silica - doped y - tzp samples were only weakened by less than 20 % . 0 ###LEFT-WALL### 2 aim 0 ###LEFT-WALL### 6 was 1 the 2 aim 2 aim 3 of 2 aim 6 was 3 of 5 study 4 this 5 study 6 was 7 to 7 to 8 compare 8 compare 10 degradation 8 compare 20 with 9 the 10 degradation 10 degradation 11 of 11 of 19 material 12 a 13 new 12 a 19 material 13 new 14 silica 14 silica 15 doped 15 doped 16 y 18 tzp 19 material 20 with 21 that 21 that 22 of 22 of 26 tzp 23 conventional 25 - 23 conventional 26 tzp 26 tzp 27 by 27 by 28 using 28 using 31 tests 29 accelerated 31 tests 30 aging 31 tests 31 tests 32 at 31 tests 37 results 31 tests 42 revealed 32 at 34 °c 33 200 34 °c 36 the 37 results 37 results 38 of 37 results 42 revealed 38 of 41 tests 39 the 41 tests 40 accelerated 41 tests 42 revealed 43 that 42 revealed 44 after 44 after 45 50 45 50 46 hours 45 50 57 damaged 46 hours 47 of 46 hours 54 tzp 46 hours 55 samples 46 hours 56 had 47 of 48 aging 48 aging 51 conventional 49 , 51 conventional 50 the 51 conventional 51 conventional 53 - 54 tzp 55 samples 56 had 57 damaged 57 damaged 58 surfaces 57 damaged 62 by 58 surfaces 59 that 58 surfaces 60 were 59 that 60 were 60 were 61 weakened 62 by 64 to 63 50 64 to 64 to 65 60 64 to 75 tzp 65 60 66 % 66 % 70 silica 66 % 72 doped 67 , 70 silica 69 the 70 silica 70 silica 71 - 72 doped 73 y 74 - 75 tzp 75 tzp 76 samples 75 tzp 77 were 75 tzp 79 weakened 75 tzp 85 . 76 samples 77 were 77 were 78 only 79 weakened 80 by 79 weakened 82 than 80 by 81 less 82 than 84 % 83 20 84 % the monoclinic content of the conventional [y] - tzp samples increased substantially to 62.7 % , however , that of silica - doped y - tzp [samples] was 18.9 % after 5 hours of aging . 0 ###LEFT-WALL### 3 content 0 ###LEFT-WALL### 23 doped 0 ###LEFT-WALL### 25 - 1 the 3 content 2 monoclinic 3 content 3 content 4 of 3 content 10 samples 3 content 11 increased 3 content 19 that 3 content 23 doped 4 of 9 tzp 5 the 9 tzp 6 conventional 8 - 6 conventional 9 tzp 10 samples 11 increased 11 increased 12 substantially 11 increased 13 to 11 increased 17 however 13 to 15 % 14 62.7 15 % 16 , 17 however 17 however 18 , 18 , 19 that 19 that 20 of 19 that 22 - 20 of 21 silica 23 doped 24 y 25 - 26 tzp 25 - 28 was 25 - 36 . 26 tzp 28 was 28 was 30 % 29 18.9 30 % 30 % 31 after 30 % 34 of 31 after 33 hours 32 5 33 hours 34 of 35 aging it was concluded that a new type of silica - [doped] y - tzp , created by adding a small amount of silica to y - tzp , will be more resistant to low temperature degradation than conventional y - tzp . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 3 concluded 0 ###LEFT-WALL### 40 - 1 it 2 was 2 was 3 concluded 3 concluded 4 that 4 that 9 silica 4 that 16 created 5 a 7 type 6 new 7 type 7 type 8 of 7 type 9 silica 8 of 9 silica 9 silica 13 - 9 silica 16 created 10 - 13 - 12 y 13 - 13 - 14 tzp 13 - 15 , 16 created 17 by 16 created 39 y 17 by 18 adding 18 adding 23 silica 18 adding 34 low 19 a 21 amount 20 small 21 amount 21 amount 22 of 21 amount 23 silica 22 of 23 silica 23 silica 24 to 23 silica 27 tzp 23 silica 29 will 24 to 25 y 26 - 27 tzp 27 tzp 28 , 29 will 30 be 30 be 31 more 30 be 32 resistant 32 resistant 33 to 32 resistant 34 low 33 to 34 low 34 low 36 degradation 34 low 37 than 35 temperature 36 degradation 37 than 38 conventional 40 - 41 tzp 40 - 42 . none none the anti - aging effects of phloridzin on the yeast saccharomyces cerevisiae were investigated by employing a replicative lifespan assay of the k6001 yeast strain . 0 ###LEFT-WALL### 1 none 0 ###LEFT-WALL### 27 strain 0 ###LEFT-WALL### 28 . 1 none 3 the 1 none 16 investigated 1 none 27 strain 2 none 3 the 3 the 7 effects 3 the 15 were 3 the 16 investigated 4 anti 5 - 4 anti 7 effects 6 aging 7 effects 7 effects 8 of 7 effects 15 were 8 of 9 phloridzin 9 phloridzin 10 on 10 on 14 cerevisiae 11 the 14 cerevisiae 12 yeast 14 cerevisiae 13 saccharomyces 14 cerevisiae 16 investigated 17 by 17 by 18 employing 18 employing 22 assay 19 a 20 replicative 19 a 22 assay 20 replicative 22 assay 21 lifespan 22 assay 22 assay 23 of 23 of 26 yeast 24 the 26 yeast 25 k6001 26 yeast after administrating phloridzin at doses of 3 , 10 , and 30 µm , the lifespan of the yeast was significantly prolonged in comparison with the untreated group ( p<0.01 , p<0.001 ) . 0 ###LEFT-WALL### 16 lifespan 0 ###LEFT-WALL### 22 prolonged 0 ###LEFT-WALL### 34 . 1 after 2 administrating 1 after 14 , 1 after 16 lifespan 2 administrating 3 phloridzin 2 administrating 4 at 4 at 11 and 5 doses 6 of 5 doses 11 and 6 of 7 3 7 3 9 10 8 , 9 10 9 10 10 , 11 and 13 µm 12 30 13 µm 15 the 16 lifespan 16 lifespan 17 of 16 lifespan 20 was 17 of 19 yeast 18 the 19 yeast 20 was 22 prolonged 21 significantly 22 prolonged 22 prolonged 23 in 22 prolonged 25 with 23 in 24 comparison 25 with 28 group 26 the 28 group 27 untreated 28 group 28 group 32 p<0.001 29 ( 32 p<0.001 30 p<0.01 31 , 30 p<0.01 32 p<0.001 32 p<0.001 33 ) to determine the mechanism of action , anti - oxidative experiments and ros assay were performed . 0 ###LEFT-WALL### 1 to 0 ###LEFT-WALL### 2 determine 0 ###LEFT-WALL### 17 . 1 to 2 determine 2 determine 12 and 2 determine 16 performed 3 the 4 mechanism 4 mechanism 5 of 4 mechanism 7 , 5 of 6 action 7 , 11 experiments 7 , 12 and 8 anti 9 - 8 anti 11 experiments 10 oxidative 11 experiments 12 and 14 assay 12 and 15 were 13 ros 14 assay 15 were 16 performed phloridzin improved the viability of the yeast dose - [dependently] under oxidative stress by 7.5 mm [h] ( 2 [ ] ( 2 ) , and a low dose of phloridzin inhibited ros of the yeast . 0 ###LEFT-WALL### 1 phloridzin 0 ###LEFT-WALL### 2 improved 0 ###LEFT-WALL### 25 , 0 ###LEFT-WALL### 36 yeast 1 phloridzin 2 improved 2 improved 4 viability 3 the 4 viability 4 viability 5 of 5 of 8 dose 6 the 8 dose 7 yeast 8 dose 8 dose 11 under 9 - 11 under 11 under 13 stress 11 under 24 ) 12 oxidative 13 stress 13 stress 14 by 13 stress 19 2 14 by 16 mm 15 7.5 16 mm 18 ( 19 2 19 2 22 ( 19 2 24 ) 21 ] 22 ( 22 ( 23 2 24 ) 25 , 25 , 28 low 25 , 31 phloridzin 26 and 27 a 26 and 28 low 27 a 28 low 28 low 29 dose 28 low 31 phloridzin 29 dose 30 of 31 phloridzin 32 inhibited 32 inhibited 33 ros 33 ros 35 the 34 of 35 the further , sod1 , sod2 , and sir2 gene expression was examined by reverse transcription - polymerase chain reaction ( rt - pcr ) , and was found to be significantly increased . 0 ###LEFT-WALL### 10 expression 0 ###LEFT-WALL### 26 and 0 ###LEFT-WALL### 33 . 1 further 2 , 1 further 10 expression 3 sod1 4 , 4 , 5 sod2 4 , 7 and 6 , 7 and 7 and 8 sir2 7 and 10 expression 9 gene 10 expression 10 expression 26 and 11 was 12 examined 11 was 26 and 12 examined 13 by 13 by 15 transcription 14 reverse 15 transcription 15 transcription 19 reaction 16 - 19 reaction 17 polymerase 19 reaction 18 chain 19 reaction 19 reaction 21 rt 19 reaction 25 , 20 ( 21 rt 21 rt 23 pcr 21 rt 25 , 22 - 23 pcr 23 pcr 24 ) 26 and 27 was 26 and 29 to 27 was 28 found 29 to 30 be 30 be 32 increased 31 significantly 32 increased finally , superoxide dismutase ( [sod] [ )(and sirt1 activity assays showed that phloridzin notably increased the activity of sod and sirt1 . 0 ###LEFT-WALL### 8 )(and 0 ###LEFT-WALL### 12 showed 0 ###LEFT-WALL### 23 . 1 finally 2 , 1 finally 8 )(and 3 superoxide 4 dismutase 4 dismutase 8 )(and 5 ( 8 )(and 8 )(and 11 assays 8 )(and 12 showed 9 sirt1 11 assays 10 activity 11 assays 12 showed 14 phloridzin 12 showed 18 activity 12 showed 21 and 13 that 14 phloridzin 14 phloridzin 16 increased 15 notably 16 increased 17 the 18 activity 18 activity 19 of 19 of 20 sod 21 and 22 sirt1 these results suggest that sod and sir2 have important roles in phloridzin - regulated lifespan extension of yeast , and potentially anti - aging effects for mammalian cells via sirt1 . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 8 have 0 ###LEFT-WALL### 31 . 1 these 2 results 2 results 3 suggest 3 suggest 4 that 4 that 7 sir2 4 that 8 have 5 sod 6 and 6 and 7 sir2 8 have 20 and 8 have 26 for 8 have 29 via 9 important 10 roles 10 roles 11 in 10 roles 20 and 11 in 12 phloridzin 12 phloridzin 16 extension 13 - 16 extension 14 regulated 16 extension 15 lifespan 16 extension 16 extension 17 of 16 extension 19 , 17 of 18 yeast 20 and 21 potentially 20 and 25 effects 22 anti 23 - 22 anti 25 effects 24 aging 25 effects 26 for 28 cells 27 mammalian 28 cells 29 via 30 sirt1 background : until recently , population - based data of cancer survival in germany mostly relied on one registry covering ∼1 [million] people ( 1.3 % of the german population ) . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 5 , 1 background 2 : 2 : 3 until 3 until 4 recently 5 , 6 population 5 , 7 - 7 - 9 data 7 - 16 relied 7 - 32 . 8 based 9 data 9 data 10 of 9 data 16 relied 10 of 12 survival 11 cancer 12 survival 12 survival 13 in 13 in 14 germany 15 mostly 16 relied 16 relied 17 on 17 on 19 registry 18 one 19 registry 19 registry 20 covering 20 covering 23 people 21 ∼1 23 people 23 people 26 % 24 ( 26 % 25 1.3 26 % 26 % 27 of 26 % 31 ) 27 of 30 population 28 the 30 population 29 german 30 population here , we provide up - to [-] date cancer survival estimates for germany based on data from 11 population - based cancer registries , covering 33 million people and compare them to survival estimates from the united states . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 30 and 0 ###LEFT-WALL### 40 . 1 here 2 , 1 here 3 we 3 we 30 and 4 provide 5 up 4 provide 7 to 4 provide 26 covering 4 provide 30 and 6 - 7 to 7 to 9 date 7 to 25 , 9 date 12 estimates 10 cancer 11 survival 11 survival 12 estimates 12 estimates 13 for 12 estimates 15 based 13 for 14 germany 15 based 16 on 16 on 17 data 17 data 18 from 17 data 24 registries 18 from 20 population 19 11 20 population 21 - 24 registries 22 based 23 cancer 23 cancer 24 registries 24 registries 25 , 26 covering 28 million 26 covering 29 people 27 33 28 million 28 million 29 people 30 and 31 compare 30 and 33 to 30 and 36 from 30 and 39 states 31 compare 32 them 33 to 35 estimates 34 survival 35 estimates 36 from 38 united 37 the 38 united patients and methods : cancer patients diagnosed in 1997 - 2006 were included . 0 ###LEFT-WALL### 3 methods 0 ###LEFT-WALL### 4 : 0 ###LEFT-WALL### 14 . 1 patients 2 and 2 and 3 methods 4 : 6 patients 4 : 13 included 5 cancer 6 patients 6 patients 7 diagnosed 6 patients 12 were 7 diagnosed 8 in 8 in 10 - 9 1997 10 - 10 - 11 2006 12 were 13 included period analysis was employed to calculate 5 - year relative survival for 38 cancers for 2002 - 2006 . 0 ###LEFT-WALL### 2 analysis 0 ###LEFT-WALL### 4 employed 0 ###LEFT-WALL### 17 - 1 period 2 analysis 2 analysis 3 was 3 was 4 employed 4 employed 5 to 4 employed 6 calculate 5 to 6 calculate 6 calculate 7 5 7 5 11 survival 8 - 11 survival 9 year 10 relative 10 relative 11 survival 11 survival 12 for 11 survival 17 - 12 for 14 cancers 13 38 14 cancers 14 cancers 15 for 15 for 16 2002 17 - 18 2006 17 - 19 . german and usa survival rates were compared utilizing the surveillance , epidemiology and end results 13 database . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 18 . 1 german 2 and 2 and 3 usa 2 and 5 rates 2 and 6 were 2 and 7 compared 2 and 8 utilizing 4 survival 5 rates 5 rates 6 were 8 utilizing 13 and 9 the 10 surveillance 10 surveillance 11 , 11 , 12 epidemiology 11 , 13 and 13 and 17 database 14 end 15 results 15 results 16 13 15 results 17 database for the majority of cancers , german survival estimates were close to or [below] [those] in the united states . 0 ###LEFT-WALL### 9 estimates 0 ###LEFT-WALL### 10 were 0 ###LEFT-WALL### 20 . 1 for 5 cancers 1 for 6 , 1 for 9 estimates 2 the 3 majority 3 majority 4 of 3 majority 5 cancers 4 of 5 cancers 7 german 9 estimates 8 survival 9 estimates 9 estimates 10 were 10 were 13 or 11 close 12 to 12 to 13 or 13 or 16 in 13 or 19 states 17 the 19 states 18 united 19 states exceptions with higher survival in germany were cancers of the stomach , pancreas and kidney and hodgkin 's lymphoma . 0 ###LEFT-WALL### 1 exceptions 0 ###LEFT-WALL### 7 were 0 ###LEFT-WALL### 20 . 1 exceptions 2 with 1 exceptions 7 were 2 with 4 survival 3 higher 4 survival 4 survival 5 in 5 in 6 germany 7 were 8 cancers 8 cancers 9 of 9 of 16 and 10 the 11 stomach 11 stomach 12 , 12 , 13 pancreas 12 , 14 and 14 and 15 kidney 14 and 16 and 16 and 19 lymphoma 17 hodgkin 18 's 18 's 19 lymphoma conclusions : german cancer survival estimates are mostly higher than the 2000 - 2002 pan - european estimates . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 6 estimates 2 : 7 are 3 german 5 survival 4 cancer 5 survival 5 survival 6 estimates 6 estimates 7 are 7 are 8 mostly 7 are 9 higher 9 higher 10 than 10 than 15 pan 11 the 15 pan 12 2000 13 - 13 - 14 2002 13 - 15 pan 15 pan 18 estimates 16 - 18 estimates 17 european 18 estimates 18 estimates 19 . further research is needed to investigate causes responsible for differences between german and usa cancer survival rates . 0 ###LEFT-WALL### 2 research 0 ###LEFT-WALL### 6 investigate 0 ###LEFT-WALL### 18 . 1 further 2 research 2 research 3 is 3 is 4 needed 4 needed 5 to 5 to 6 investigate 6 investigate 7 causes 7 causes 8 responsible 8 responsible 9 for 8 responsible 11 between 9 for 10 differences 11 between 13 and 12 german 13 and 13 and 17 rates 14 usa 15 cancer 15 cancer 17 rates 16 survival 17 rates the prevalence of erectile dysfunction is high in men of all ages and increases greatly in the elderly . 0 ###LEFT-WALL### 2 prevalence 0 ###LEFT-WALL### 6 is 0 ###LEFT-WALL### 19 . 1 the 2 prevalence 2 prevalence 3 of 2 prevalence 6 is 3 of 5 dysfunction 4 erectile 5 dysfunction 6 is 7 high 7 high 8 in 7 high 15 greatly 7 high 16 in 8 in 13 and 9 men 10 of 9 men 13 and 10 of 12 ages 11 all 12 ages 13 and 14 increases 16 in 18 elderly 17 the 18 elderly in particular , severity and prevalence both increase with aging . 0 ###LEFT-WALL### 5 and 0 ###LEFT-WALL### 8 increase 0 ###LEFT-WALL### 11 . 1 in 2 particular 2 particular 3 , 2 particular 5 and 4 severity 5 and 5 and 6 prevalence 5 and 8 increase 7 both 8 increase 8 increase 9 with 9 with 10 aging because erectile dysfunction is a symptom , physicians should diagnose underlying pathologies that might lead to it instead of focusing only on finding a viable treatment . 0 ###LEFT-WALL### 8 physicians 0 ###LEFT-WALL### 10 diagnose 0 ###LEFT-WALL### 27 . 1 because 3 dysfunction 1 because 4 is 1 because 7 , 1 because 8 physicians 2 erectile 3 dysfunction 3 dysfunction 4 is 4 is 6 symptom 5 a 6 symptom 8 physicians 9 should 9 should 10 diagnose 10 diagnose 12 pathologies 10 diagnose 19 of 11 underlying 12 pathologies 12 pathologies 13 that 12 pathologies 14 might 13 that 14 might 14 might 15 lead 15 lead 16 to 16 to 17 it 18 instead 19 of 19 of 20 focusing 20 focusing 21 only 21 only 22 on 22 on 23 finding 23 finding 26 treatment 24 a 26 treatment 25 viable 26 treatment physical inactivity [negatively] impacts on erectile function ; experimental and clinical exercise interventions have been shown to improve sexual responses and overall cardiovascular health . 0 ###LEFT-WALL### 4 impacts 0 ###LEFT-WALL### 7 function 0 ###LEFT-WALL### 8 ; 0 ###LEFT-WALL### 25 . 1 physical 4 impacts 2 inactivity 4 impacts 4 impacts 5 on 4 impacts 7 function 5 on 6 erectile 8 ; 13 interventions 8 ; 16 shown 9 experimental 10 and 10 and 11 clinical 10 and 12 exercise 12 exercise 13 interventions 13 interventions 14 have 14 have 15 been 15 been 16 shown 16 shown 17 to 17 to 18 improve 18 improve 21 and 19 sexual 20 responses 20 responses 21 and 21 and 24 health 22 overall 24 health 23 cardiovascular 24 health several studies have confirmed that combining 2 interventions ( mediterranean [diet] and physical activity ) provides additional benefit [to] erectile function , likely via reduced metabolic disturbances ( eg , inflammatory markers , insulin resistance ) , decreased visceral adipose tissue , and improvement in vascular function [(] eg , increased endothelial function [ )( 0 ###LEFT-WALL### 1 several 0 ###LEFT-WALL### 22 , 0 ###LEFT-WALL### 55 )( 1 several 2 studies 1 several 16 provides 1 several 21 function 2 studies 3 have 3 have 4 confirmed 4 confirmed 5 that 5 that 6 combining 5 that 16 provides 6 combining 8 interventions 6 combining 16 provides 7 2 8 interventions 8 interventions 12 and 9 ( 12 and 10 mediterranean 12 and 12 and 14 activity 12 and 15 ) 13 physical 14 activity 16 provides 20 erectile 17 additional 18 benefit 18 benefit 20 erectile 22 , 43 and 22 , 53 function 23 likely 24 via 23 likely 43 and 24 via 27 disturbances 25 reduced 27 disturbances 26 metabolic 27 disturbances 27 disturbances 29 eg 27 disturbances 41 tissue 28 ( 29 eg 29 eg 32 markers 29 eg 37 , 30 , 32 markers 31 inflammatory 32 markers 32 markers 35 resistance 32 markers 37 , 33 , 35 resistance 34 insulin 35 resistance 35 resistance 36 ) 37 , 41 tissue 38 decreased 40 adipose 39 visceral 40 adipose 40 adipose 41 tissue 41 tissue 42 , 42 , 43 and 43 and 44 improvement 43 and 50 , 43 and 51 increased 43 and 53 function 44 improvement 45 in 45 in 49 eg 46 vascular 49 eg 47 function 49 eg 51 increased 52 endothelial this brief review shows the main clinical evidence of benefits induced by physical activity on erectile and endothelial dysfunction . 0 ###LEFT-WALL### 3 review 0 ###LEFT-WALL### 4 shows 0 ###LEFT-WALL### 20 . 1 this 2 brief 2 brief 3 review 3 review 4 shows 4 shows 6 main 4 shows 8 evidence 4 shows 15 on 5 the 6 main 7 clinical 8 evidence 8 evidence 9 of 9 of 10 benefits 10 benefits 11 induced 11 induced 12 by 12 by 14 activity 13 physical 14 activity 15 on 17 and 16 erectile 17 and 17 and 19 dysfunction 18 endothelial 19 dysfunction the literature shows that erectile dysfunction in middle [-] aged men is often an early event in endothelial damage , and physical activity is able to improve both erectile and endothelial dysfunction . 0 ###LEFT-WALL### 2 literature 0 ###LEFT-WALL### 3 shows 0 ###LEFT-WALL### 21 and 0 ###LEFT-WALL### 27 improve 0 ###LEFT-WALL### 33 . 1 the 2 literature 2 literature 3 shows 3 shows 4 that 4 that 6 dysfunction 4 that 12 is 5 erectile 6 dysfunction 6 dysfunction 7 in 6 dysfunction 12 is 7 in 11 men 8 middle 10 aged 10 aged 11 men 12 is 13 often 12 is 16 event 14 an 16 event 15 early 16 event 16 event 17 in 17 in 19 damage 18 endothelial 19 damage 20 , 21 and 21 and 23 activity 21 and 24 is 22 physical 23 activity 23 activity 24 is 24 is 25 able 25 able 26 to 26 to 27 improve 27 improve 30 and 28 both 30 and 29 erectile 30 and 30 and 32 dysfunction 31 endothelial 32 dysfunction there are conflicting data regarding the effects of exercise on androgen status . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 are 0 ###LEFT-WALL### 13 . 1 there 2 are 2 are 4 data 3 conflicting 4 data 4 data 5 regarding 5 regarding 7 effects 5 regarding 10 on 6 the 7 effects 7 effects 8 of 8 of 9 exercise 10 on 12 status 11 androgen 12 status in clinical practice it would be recommended to add regular physical activity to balanced diet and drugs to achieve better therapeutic results . 0 ###LEFT-WALL### 15 diet 0 ###LEFT-WALL### 16 and 0 ###LEFT-WALL### 23 . 1 in 3 practice 1 in 15 diet 2 clinical 3 practice 3 practice 4 it 3 practice 13 to 3 practice 14 balanced 4 it 5 would 5 would 6 be 6 be 7 recommended 7 recommended 8 to 8 to 9 add 9 add 12 activity 9 add 13 to 10 regular 12 activity 11 physical 12 activity 16 and 17 drugs 16 and 20 better 17 drugs 18 to 17 drugs 19 achieve 17 drugs 20 better 18 to 19 achieve 20 better 22 results 21 therapeutic 22 results background and purpose : cerebral microbleeds ( mbs ) are frequently detected in patients with [stroke] , especially those who experience intracerebral hemorrhage . 0 ###LEFT-WALL### 3 purpose 0 ###LEFT-WALL### 4 : 1 background 2 and 2 and 3 purpose 3 purpose 4 : 4 : 5 cerebral 5 cerebral 6 microbleeds 5 cerebral 15 with 5 cerebral 19 those 6 microbleeds 8 mbs 6 microbleeds 10 are 7 ( 8 mbs 8 mbs 9 ) 10 are 12 detected 11 frequently 12 detected 12 detected 13 in 12 detected 15 with 13 in 14 patients 17 , 18 especially 17 , 19 those 19 those 20 who 19 those 21 experience 19 those 24 . 20 who 21 experience 21 experience 23 hemorrhage 22 intracerebral 23 hemorrhage however , the clinical significance of mbs in subjects without cerebrovascular disease is still unclear . 0 ###LEFT-WALL### 5 significance 0 ###LEFT-WALL### 13 is 0 ###LEFT-WALL### 16 . 1 however 2 , 1 however 5 significance 3 the 5 significance 4 clinical 5 significance 5 significance 6 of 5 significance 13 is 6 of 7 mbs 7 mbs 8 in 8 in 9 subjects 9 subjects 10 without 10 without 12 disease 11 cerebrovascular 12 disease 13 is 14 still 13 is 15 unclear 14 still 15 unclear we performed a prospective study to determine whether the presence of mbs provides useful prognostic information in healthy elderly individuals . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 performed 0 ###LEFT-WALL### 21 . 1 we 2 performed 2 performed 5 study 2 performed 6 to 2 performed 17 in 3 a 4 prospective 3 a 5 study 4 prospective 5 study 6 to 7 determine 7 determine 8 whether 8 whether 10 presence 8 whether 13 provides 9 the 10 presence 10 presence 11 of 10 presence 13 provides 11 of 12 mbs 13 provides 16 information 14 useful 16 information 15 prognostic 16 information 17 in 20 individuals 18 healthy 20 individuals 19 elderly 20 individuals methods : we tracked 2102 subjects ( mean age , 62.1 years ) over a mean interval of 3.6 years after they voluntarily participated in the brain checkup system at the shimane institute of health science . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 3 we 2 : 4 tracked 2 : 37 . 3 we 4 tracked 4 tracked 6 subjects 4 tracked 14 over 4 tracked 21 after 5 2102 6 subjects 6 subjects 9 age 7 ( 9 age 8 mean 9 age 9 age 12 years 9 age 13 ) 10 , 12 years 11 62.1 12 years 12 years 13 ) 14 over 17 interval 15 a 16 mean 15 a 17 interval 16 mean 17 interval 17 interval 18 of 18 of 20 years 19 3.6 20 years 21 after 22 they 21 after 24 participated 22 they 24 participated 23 voluntarily 24 participated 24 participated 25 in 24 participated 30 at 25 in 29 system 26 the 29 system 27 brain 29 system 28 checkup 29 system 30 at 33 institute 31 the 33 institute 32 shimane 33 institute 33 institute 34 of 34 of 36 science 35 health 36 science an initial assessment was performed to document the presence of mbs and silent ischemic brain lesions and to map the location of the mbs . 0 ###LEFT-WALL### 3 assessment 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 25 . 1 an 3 assessment 2 initial 3 assessment 3 assessment 4 was 4 was 17 and 5 performed 6 to 5 performed 16 lesions 5 performed 17 and 6 to 7 document 7 document 9 presence 8 the 9 presence 9 presence 10 of 10 of 12 and 11 mbs 12 and 12 and 15 brain 13 silent 15 brain 14 ischemic 15 brain 17 and 18 to 17 and 19 map 18 to 19 map 19 map 21 location 20 the 21 location 21 location 22 of 22 of 24 mbs 23 the 24 mbs during the [follow] [-] up period , we obtained information about stroke events that occurred in each subject . 0 ###LEFT-WALL### 8 we 0 ###LEFT-WALL### 9 obtained 0 ###LEFT-WALL### 19 . 1 during 6 period 1 during 7 , 1 during 8 we 2 the 6 period 5 up 6 period 8 we 9 obtained 9 obtained 10 information 9 obtained 11 about 11 about 13 events 12 stroke 13 events 13 events 14 that 13 events 15 occurred 14 that 15 occurred 15 occurred 16 in 16 in 18 subject 17 each 18 subject results : mbs were detected in 93 of the 2102 subjects ( 4.4 % ) . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 3 mbs 2 : 5 detected 2 : 16 . 3 mbs 4 were 4 were 5 detected 5 detected 6 in 6 in 7 93 7 93 8 of 8 of 11 subjects 9 the 10 2102 10 2102 11 subjects 11 subjects 14 % 12 ( 14 % 13 4.4 14 % 14 % 15 ) strokes occurred in 44 subjects ( 2.1 % ) during the [follow] [-] up period . 0 ###LEFT-WALL### 1 strokes 0 ###LEFT-WALL### 2 occurred 0 ###LEFT-WALL### 16 . 1 strokes 2 occurred 2 occurred 3 in 2 occurred 10 during 3 in 5 subjects 4 44 5 subjects 5 subjects 8 % 6 ( 8 % 7 2.1 8 % 8 % 9 ) 10 during 15 period 11 the 15 period 14 up 15 period they were significantly more common among subjects with mbs . 0 ###LEFT-WALL### 1 they 0 ###LEFT-WALL### 2 were 0 ###LEFT-WALL### 10 . 1 they 2 were 2 were 5 common 3 significantly 4 more 4 more 5 common 5 common 6 among 5 common 8 with 6 among 7 subjects 8 with 9 mbs age and hypertension were independent risk factors for mbs . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 4 were 0 ###LEFT-WALL### 10 . 1 age 2 and 2 and 3 hypertension 2 and 4 were 4 were 7 factors 5 independent 7 factors 6 risk 7 factors 7 factors 8 for 8 for 9 mbs the presence of mbs was more strongly associated with a deep brain hemorrhage [(] hazard ratio , 50.2 ; 95 % ci , 16.7 to 150.9 ) than ischemic stroke [(] hazard ratio , 4.48 ; 95 % ci , [2.20] [to] 12.2 [ )( 0 ###LEFT-WALL### 2 presence 0 ###LEFT-WALL### 8 associated 0 ###LEFT-WALL### 17 , 0 ###LEFT-WALL### 45 )( 1 the 2 presence 2 presence 3 of 2 presence 5 was 3 of 4 mbs 5 was 8 associated 6 more 7 strongly 7 strongly 8 associated 8 associated 9 with 9 with 16 ratio 10 a 16 ratio 11 deep 12 brain 12 brain 16 ratio 13 hemorrhage 15 hazard 15 hazard 16 ratio 17 , 18 50.2 17 , 19 ; 19 ; 33 ratio 19 ; 34 , 20 95 21 % 21 % 33 ratio 22 ci 25 to 22 ci 33 ratio 23 , 25 to 24 16.7 25 to 25 to 26 150.9 25 to 27 ) 28 than 29 ischemic 29 ischemic 30 stroke 30 stroke 33 ratio 32 hazard 33 ratio 34 , 35 4.48 34 , 36 ; 36 ; 39 ci 36 ; 40 , 37 95 39 ci 38 % 39 ci 40 , 43 12.2 all hemorrhagic strokes occurred in deep brain regions , and they were associated with mbs located in the deep brain region . 0 ###LEFT-WALL### 3 strokes 0 ###LEFT-WALL### 4 occurred 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 22 . 1 all 3 strokes 2 hemorrhagic 3 strokes 3 strokes 4 occurred 4 occurred 5 in 5 in 8 regions 6 deep 7 brain 7 brain 8 regions 9 , 10 and 10 and 11 they 10 and 13 associated 11 they 12 were 12 were 13 associated 13 associated 14 with 14 with 15 mbs 15 mbs 16 located 16 located 17 in 17 in 21 region 18 the 21 region 19 deep 20 brain 20 brain 21 region conclusions : this longitudinal study demonstrated that the presence of mbs can be used to predict hemorrhagic and ischemic stroke , even in healthy elderly individuals . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 21 , 0 ###LEFT-WALL### 27 . 1 conclusions 2 : 2 : 5 study 3 this 5 study 4 longitudinal 5 study 5 study 6 demonstrated 5 study 7 that 5 study 16 predict 7 that 9 presence 7 that 14 used 8 the 9 presence 9 presence 10 of 9 presence 12 can 10 of 11 mbs 12 can 13 be 13 be 14 used 14 used 15 to 14 used 16 predict 15 to 16 predict 16 predict 18 and 17 hemorrhagic 18 and 18 and 20 stroke 19 ischemic 20 stroke 21 , 22 even 22 even 23 in 22 even 26 individuals 24 healthy 26 individuals 25 elderly 26 individuals objective : hearing and visual impairments are commonly viewed separately in research and service provision , but they often occur together as dual sensory impairment or dsi in older populations . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 2 : 4 and 2 : 9 viewed 2 : 17 but 2 : 31 . 3 hearing 4 and 4 and 6 impairments 4 and 7 are 5 visual 6 impairments 7 are 9 viewed 8 commonly 9 viewed 9 viewed 10 separately 9 viewed 11 in 11 in 13 and 12 research 13 and 13 and 15 provision 13 and 16 , 14 service 15 provision 17 but 18 they 17 but 20 occur 18 they 20 occur 19 often 20 occur 20 occur 21 together 20 occur 22 as 22 as 26 or 23 dual 25 impairment 24 sensory 25 impairment 25 impairment 26 or 26 or 27 dsi 26 or 28 in 28 in 30 populations 29 older 30 populations this article examines the frequency and effects of dsi in older age and notes limitations in the evidence . 0 ###LEFT-WALL### 2 article 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 19 . 1 this 2 article 2 article 13 and 3 examines 6 and 3 examines 13 and 4 the 5 frequency 5 frequency 6 and 6 and 7 effects 6 and 8 of 6 and 10 in 8 of 9 dsi 10 in 12 age 11 older 12 age 13 and 14 notes 14 notes 15 limitations 14 notes 16 in 16 in 18 evidence 17 the 18 evidence methods : search of electronic databases of published papers . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 10 . 1 methods 2 : 2 : 3 search 3 search 4 of 4 of 6 databases 5 electronic 6 databases 6 databases 7 of 7 of 9 papers 8 published 9 papers results : dsi diminishes communication and well - being and can cause social isolation , depression , reduced independence , mortality , and cognitive impairment . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 26 . 2 : 3 dsi 2 : 18 reduced 3 dsi 10 and 3 dsi 16 depression 3 dsi 18 reduced 4 diminishes 9 being 4 diminishes 10 and 5 communication 6 and 6 and 7 well 6 and 8 - 6 and 9 being 10 and 11 can 11 can 12 cause 12 cause 14 isolation 13 social 14 isolation 15 , 16 depression 16 depression 17 , 18 reduced 23 and 19 independence 20 , 20 , 21 mortality 20 , 23 and 22 , 23 and 23 and 25 impairment 24 cognitive 25 impairment discussion : although intuitively dsi may be expected to have additional impacts over single sensory impairment , research findings are inconclusive . 0 ###LEFT-WALL### 1 discussion 0 ###LEFT-WALL### 8 expected 0 ###LEFT-WALL### 17 , 0 ###LEFT-WALL### 22 . 1 discussion 2 : 2 : 3 although 3 although 5 dsi 4 intuitively 5 dsi 5 dsi 6 may 6 may 7 be 7 be 8 expected 8 expected 9 to 8 expected 10 have 9 to 10 have 10 have 12 impacts 10 have 13 over 11 additional 12 impacts 13 over 16 impairment 14 single 16 impairment 15 sensory 16 impairment 17 , 19 findings 17 , 20 are 18 research 19 findings 19 findings 20 are 20 are 21 inconclusive services and supports required by people with dsi are simply a combination of those required by people with single vision and hearing loss , taking [account] of the unique communication difficulties posed by dsi . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 9 are 0 ###LEFT-WALL### 21 and 0 ###LEFT-WALL### 35 . 1 services 2 and 2 and 3 supports 2 and 4 required 2 and 7 with 2 and 9 are 4 required 5 by 5 by 6 people 7 with 8 dsi 9 are 10 simply 9 are 12 combination 11 a 12 combination 12 combination 13 of 12 combination 16 by 13 of 14 those 14 those 15 required 16 by 17 people 17 people 18 with 18 with 20 vision 19 single 20 vision 21 and 25 taking 21 and 32 posed 22 hearing 23 loss 22 hearing 24 , 22 hearing 25 taking 25 taking 27 of 25 taking 32 posed 27 of 31 difficulties 28 the 31 difficulties 29 unique 30 communication 30 communication 31 difficulties 32 posed 33 by 33 by 34 dsi background : aging is responsible for degenerative changes in all cartilage elements , thus impairing its properties and healing potential . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 3 aging 2 : 4 is 3 aging 4 is 4 is 5 responsible 5 responsible 6 for 5 responsible 9 in 6 for 8 changes 7 degenerative 8 changes 9 in 12 elements 10 all 12 elements 11 cartilage 12 elements 12 elements 15 impairing 13 , 15 impairing 14 thus 15 impairing 15 impairing 18 and 15 impairing 21 . 16 its 17 properties 17 properties 18 and 18 and 20 potential 19 healing 20 potential most studies on surgical procedures for cartilage focus on young patients because these procedures are generally not considered suitable for older patients . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 8 focus 0 ###LEFT-WALL### 23 . 1 most 2 studies 2 studies 3 on 2 studies 8 focus 3 on 5 procedures 4 surgical 5 procedures 5 procedures 6 for 6 for 7 cartilage 8 focus 9 on 8 focus 12 because 9 on 11 patients 10 young 11 patients 12 because 14 procedures 12 because 18 considered 13 these 14 procedures 14 procedures 15 are 15 are 17 not 15 are 18 considered 16 generally 17 not 18 considered 19 suitable 19 suitable 20 for 20 for 22 patients 21 older 22 patients purpose : to analyze the clinical outcome of cartilage lesion treatment using second - generation autologous chondrocyte [implantation] ( aci ) techniques in patients more than 40 years old with no clear signs of osteoarthritis , to understand their real potential in relation to aging , the failure rate , and complications in older patients . 0 ###LEFT-WALL### 1 purpose 0 ###LEFT-WALL### 2 : 2 : 3 to 2 : 14 - 3 to 4 analyze 4 analyze 7 outcome 4 analyze 13 second 5 the 7 outcome 6 clinical 7 outcome 7 outcome 8 of 8 of 12 using 9 cartilage 12 using 10 lesion 11 treatment 11 treatment 12 using 14 - 22 techniques 15 generation 22 techniques 16 autologous 22 techniques 17 chondrocyte 20 aci 17 chondrocyte 21 ) 17 chondrocyte 22 techniques 19 ( 20 aci 20 aci 21 ) 22 techniques 23 in 22 techniques 34 of 23 in 24 patients 24 patients 29 old 24 patients 30 with 25 more 26 than 26 than 27 40 27 40 28 years 28 years 29 old 30 with 33 signs 31 no 33 signs 32 clear 33 signs 34 of 35 osteoarthritis 35 osteoarthritis 37 to 36 , 37 to 37 to 38 understand 38 understand 41 potential 39 their 41 potential 40 real 41 potential 41 potential 44 to 41 potential 51 and 42 in 43 relation 43 relation 44 to 44 to 45 aging 46 , 51 and 47 the 49 rate 48 failure 49 rate 49 rate 51 and 50 , 51 and 51 and 52 complications 51 and 53 in 51 and 56 . 53 in 55 patients 54 older 55 patients study design : case series [;] level of evidence , 4 . 0 ###LEFT-WALL### 2 design 0 ###LEFT-WALL### 3 : 0 ###LEFT-WALL### 10 , 0 ###LEFT-WALL### 12 . 1 study 2 design 2 design 3 : 3 : 7 level 4 case 5 series 5 series 7 level 7 level 8 of 8 of 9 evidence 10 , 11 4 methods : sixty - one patients [with] grade iii to iv cartilaginous lesions of the condyles with no clear signs of osteoarthritis and a minimum age of 40 years were treated with second [-] generation aci and prospectively evaluated at 5 years ' follow - up . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 4 - 1 methods 2 : 2 : 3 sixty 4 - 5 one 5 one 6 patients 5 one 8 grade 6 patients 8 grade 8 grade 9 iii 8 grade 10 to 10 to 13 lesions 11 iv 13 lesions 12 cartilaginous 13 lesions 13 lesions 14 of 13 lesions 17 with 13 lesions 21 of 14 of 16 condyles 15 the 16 condyles 17 with 20 signs 18 no 20 signs 19 clear 20 signs 21 of 23 and 22 osteoarthritis 23 and 23 and 26 age 23 and 27 of 24 a 25 minimum 24 a 26 age 25 minimum 26 age 27 of 28 40 28 40 29 years 28 40 37 and 29 years 30 were 30 were 37 and 31 treated 32 with 31 treated 36 aci 31 treated 37 and 32 with 35 generation 33 second 35 generation 37 and 39 evaluated 38 prospectively 39 evaluated 39 evaluated 43 ' 39 evaluated 44 follow 40 at 41 5 40 at 43 ' 42 years 43 ' 43 ' 44 follow 44 follow 46 up 45 - 46 up 46 up 47 . twenty - two patients were treated with arthroscopic hyalograft c implantation , and 39 underwent the open chondro - gide maci procedure . 0 ###LEFT-WALL### 4 patients 0 ###LEFT-WALL### 6 treated 0 ###LEFT-WALL### 13 and 1 twenty 2 - 2 - 3 two 2 - 4 patients 4 patients 5 were 5 were 6 treated 6 treated 7 with 7 with 11 implantation 8 arthroscopic 11 implantation 9 hyalograft 10 c 9 hyalograft 11 implantation 12 , 13 and 13 and 14 39 13 and 15 underwent 14 39 15 underwent 15 underwent 18 chondro 16 the 18 chondro 17 open 18 chondro 18 chondro 22 procedure 19 - 22 procedure 20 gide 21 maci 21 maci 22 procedure 22 procedure 23 . results : a significant improvement in both subjective and objective evaluations was observed . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 5 improvement 2 : 13 observed 2 : 14 . 3 a 4 significant 3 a 5 improvement 4 significant 5 improvement 5 improvement 6 in 5 improvement 12 was 6 in 11 evaluations 7 both 11 evaluations 8 subjective 9 and 9 and 10 objective 9 and 11 evaluations 12 was 13 observed the international knee documentation committee ( ikdc ) subjective score improved from 36.8 ± 8.4 to 68.1 ± 21.8 at the final evaluation . 0 ###LEFT-WALL### 10 score 0 ###LEFT-WALL### 11 improved 0 ###LEFT-WALL### 24 . 1 the 10 score 2 international 3 knee 3 knee 4 documentation 4 documentation 5 committee 5 committee 7 ikdc 6 ( 7 ikdc 7 ikdc 8 ) 7 ikdc 10 score 9 subjective 10 score 10 score 11 improved 11 improved 12 from 11 improved 16 to 11 improved 18 ± 12 from 14 ± 13 36.8 14 ± 15 8.4 16 to 16 to 17 68.1 18 ± 19 21.8 18 ± 20 at 20 at 23 evaluation 21 the 23 evaluation 22 final 23 evaluation the failure rate was 20 % . 0 ###LEFT-WALL### 3 rate 0 ###LEFT-WALL### 4 was 0 ###LEFT-WALL### 7 . 1 the 3 rate 2 failure 3 rate 3 rate 4 was 4 was 6 % 5 20 6 % a faster improvement was observed in the group treated with the arthroscopic hyalograft c technique , whereas similar scores were found at the 24 - [month] follow - up and final evaluation . 0 ###LEFT-WALL### 3 improvement 0 ###LEFT-WALL### 5 observed 0 ###LEFT-WALL### 25 - 1 a 3 improvement 2 faster 3 improvement 3 improvement 4 was 4 was 5 observed 5 observed 6 in 6 in 8 group 7 the 8 group 8 group 9 treated 9 treated 10 with 9 treated 17 whereas 10 with 15 technique 11 the 15 technique 12 arthroscopic 15 technique 13 hyalograft 14 c 13 hyalograft 15 technique 16 , 17 whereas 17 whereas 19 scores 17 whereas 21 found 17 whereas 25 - 18 similar 19 scores 19 scores 20 were 20 were 21 found 21 found 22 at 22 at 24 24 23 the 24 24 25 - 27 follow 25 - 28 - 28 - 32 evaluation 28 - 33 . 29 up 30 and 30 and 31 final 30 and 32 evaluation conclusion : a clinical improvement was found in patients more than 40 years old , who in most cases benefited from second [-] generation aci with good results lasting at [medium] - [term] follow - up . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 7 found 0 ###LEFT-WALL### 11 than 1 conclusion 2 : 3 a 5 improvement 4 clinical 5 improvement 5 improvement 6 was 6 was 7 found 7 found 8 in 7 found 10 more 7 found 11 than 8 in 9 patients 11 than 12 40 11 than 34 follow 12 40 14 old 12 40 16 who 12 40 34 follow 13 years 14 old 15 , 16 who 16 who 17 in 16 who 19 cases 16 who 30 at 16 who 32 - 17 in 18 most 19 cases 20 benefited 20 benefited 21 from 20 benefited 25 aci 20 benefited 26 with 21 from 24 generation 22 second 24 generation 26 with 28 results 27 good 28 results 28 results 29 lasting 29 lasting 30 at 34 follow 36 up 35 - 36 up 36 up 37 . however , the results were inferior with respect to those previously found for younger populations , and the failure rate [at] medium - term [follow] - up [was] also higher . 0 ###LEFT-WALL### 4 results 0 ###LEFT-WALL### 5 were 1 however 2 , 1 however 4 results 3 the 4 results 4 results 5 were 5 were 6 inferior 6 inferior 7 with 6 inferior 9 to 7 with 8 respect 9 to 17 and 10 those 12 found 10 those 17 and 11 previously 12 found 12 found 13 for 13 for 15 populations 14 younger 15 populations 16 , 17 and 17 and 24 term 17 and 27 up 18 the 24 term 19 failure 20 rate 20 rate 24 term 22 medium 23 - 22 medium 24 term 26 - 27 up 27 up 29 also 27 up 30 higher 27 up 31 . these findings were consistent in the 2 treatment groups . 0 ###LEFT-WALL### 2 findings 0 ###LEFT-WALL### 3 were 0 ###LEFT-WALL### 10 . 1 these 2 findings 2 findings 3 were 3 were 4 consistent 4 consistent 5 in 5 in 9 groups 6 the 7 2 7 2 9 groups 8 treatment 9 groups the only difference was the faster recovery when the arthroscopic approach was used . 0 ###LEFT-WALL### 3 difference 0 ###LEFT-WALL### 4 was 0 ###LEFT-WALL### 14 . 1 the 2 only 1 the 3 difference 3 difference 4 was 4 was 7 recovery 5 the 7 recovery 6 faster 7 recovery 7 recovery 8 when 8 when 11 approach 8 when 13 used 9 the 11 approach 10 arthroscopic 11 approach 11 approach 12 was 12 was 13 used chronic obstructive pulmonary [disease] ( copd ) [in] old age is an increasing problem . 0 ###LEFT-WALL### 10 age 0 ###LEFT-WALL### 11 is 0 ###LEFT-WALL### 15 . 1 chronic 10 age 2 obstructive 10 age 3 pulmonary 6 copd 3 pulmonary 10 age 5 ( 6 copd 6 copd 7 ) 9 old 10 age 10 age 11 is 11 is 14 problem 12 an 14 problem 13 increasing 14 problem understanding the features of copd in older patients is important in order to introduce effective interventions and to inform efforts for health resource allocation . 0 ###LEFT-WALL### 1 understanding 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 25 . 1 understanding 3 features 1 understanding 6 in 1 understanding 9 is 2 the 3 features 3 features 4 of 4 of 5 copd 6 in 8 patients 7 older 8 patients 9 is 10 important 10 important 11 in 10 important 13 to 11 in 12 order 13 to 17 and 14 introduce 16 interventions 14 introduce 17 and 15 effective 16 interventions 17 and 18 to 17 and 19 inform 17 and 21 for 18 to 19 inform 19 inform 20 efforts 21 for 24 allocation 22 health 24 allocation 23 resource 24 allocation features of importance to old age include increased prevalence of copd in [non] [-] smokers and rise in the rate of systemic comorbidities . 0 ###LEFT-WALL### 1 features 0 ###LEFT-WALL### 7 include 0 ###LEFT-WALL### 24 . 1 features 2 of 1 features 4 to 1 features 7 include 2 of 3 importance 4 to 6 age 5 old 6 age 7 include 9 prevalence 7 include 12 in 7 include 18 in 8 increased 9 prevalence 9 prevalence 10 of 10 of 11 copd 12 in 16 and 15 smokers 16 and 16 and 17 rise 18 in 20 rate 19 the 20 rate 20 rate 21 of 21 of 23 comorbidities 22 systemic 23 comorbidities in addition , acute exacerbations in older patients have poorer [outcome] , manifesting [by] increase in the rate of hospitalisation , greater length [of] stay , [increase] of the rate of re - hospitalisation and in mortality rate . 0 ###LEFT-WALL### 5 exacerbations 0 ###LEFT-WALL### 9 have 0 ###LEFT-WALL### 21 , 0 ###LEFT-WALL### 39 . 1 in 2 addition 1 in 3 , 1 in 5 exacerbations 4 acute 5 exacerbations 5 exacerbations 6 in 5 exacerbations 9 have 6 in 8 patients 7 older 8 patients 9 have 13 manifesting 9 have 15 increase 10 poorer 12 , 10 poorer 13 manifesting 15 increase 16 in 16 in 18 rate 17 the 18 rate 18 rate 19 of 19 of 20 hospitalisation 21 , 25 stay 21 , 26 , 22 greater 23 length 23 length 25 stay 26 , 38 rate 28 of 30 rate 28 of 38 rate 29 the 30 rate 30 rate 31 of 31 of 35 and 32 re 33 - 32 re 34 hospitalisation 32 re 35 and 35 and 36 in 36 in 37 mortality impaired cognitive functions as well as problems affecting hand joints make using inhaled medications less reliable [which] leads to further deterioration of outcome [of] care . 0 ###LEFT-WALL### 3 functions 0 ###LEFT-WALL### 11 make 0 ###LEFT-WALL### 26 . 1 impaired 3 functions 2 cognitive 3 functions 3 functions 6 as 3 functions 8 affecting 3 functions 11 make 4 as 5 well 5 well 6 as 6 as 7 problems 8 affecting 10 joints 9 hand 10 joints 11 make 12 using 11 make 15 less 11 make 18 leads 11 make 19 to 12 using 14 medications 13 inhaled 14 medications 16 reliable 18 leads 19 to 21 deterioration 20 further 21 deterioration 21 deterioration 22 of 22 of 25 care 23 outcome 25 care even for those who are competent in using inhalers , the evidence for their efficacy in older patients is not certain . 0 ###LEFT-WALL### 12 evidence 0 ###LEFT-WALL### 19 is 0 ###LEFT-WALL### 22 . 1 even 2 for 1 even 10 , 1 even 12 evidence 2 for 3 those 3 those 4 who 3 those 5 are 4 who 5 are 5 are 6 competent 6 competent 7 in 7 in 8 using 8 using 9 inhalers 11 the 12 evidence 12 evidence 13 for 12 evidence 19 is 13 for 15 efficacy 14 their 15 efficacy 15 efficacy 16 in 16 in 18 patients 17 older 18 patients 19 is 20 not 19 is 21 certain none cerebral cavernous malformations ( ccm ) are irregularly shaped and enlarged capillaries in the brain that are prone to hemorrhage , resulting in headaches , seizures , strokes and even death in patients . 0 ###LEFT-WALL### 1 none 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 28 , 0 ###LEFT-WALL### 35 . 1 none 4 malformations 1 none 8 are 1 none 11 and 2 cerebral 4 malformations 3 cavernous 4 malformations 4 malformations 6 ccm 4 malformations 8 are 5 ( 6 ccm 6 ccm 7 ) 9 irregularly 10 shaped 10 shaped 11 and 11 and 12 enlarged 11 and 13 capillaries 13 capillaries 14 in 13 capillaries 17 that 13 capillaries 18 are 14 in 16 brain 15 the 16 brain 17 that 18 are 18 are 19 prone 19 prone 20 to 19 prone 21 hemorrhage 20 to 21 hemorrhage 21 hemorrhage 23 resulting 22 , 23 resulting 23 resulting 24 in 23 resulting 28 , 24 in 25 headaches 25 headaches 27 seizures 26 , 27 seizures 27 seizures 28 , 28 , 30 and 29 strokes 30 and 30 and 31 even 31 even 32 death 31 even 33 in 33 in 34 patients the disease affects up to 0.5 % of the population and the inherited form has been linked to mutations in one of three genetic loci , ccm1 , ccm2 and ccm3 . 0 ###LEFT-WALL### 2 disease 0 ###LEFT-WALL### 3 affects 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 32 . 1 the 2 disease 2 disease 3 affects 3 affects 7 % 4 up 5 to 5 to 6 0.5 6 0.5 7 % 7 % 8 of 8 of 10 population 9 the 10 population 11 and 14 form 11 and 17 linked 12 the 14 form 13 inherited 14 form 14 form 15 has 15 has 16 been 16 been 17 linked 17 linked 18 to 17 linked 20 in 18 to 19 mutations 20 in 21 one 21 one 22 of 22 of 30 and 23 three 25 loci 24 genetic 25 loci 25 loci 26 , 26 , 27 ccm1 26 , 28 , 28 , 29 ccm2 28 , 30 and 30 and 31 ccm3 to understand the pathophysiology underlying the vascular lesions in ccm , it is critical to develop a reproducible mouse genetic model of this disease . 0 ###LEFT-WALL### 1 to 0 ###LEFT-WALL### 11 , 0 ###LEFT-WALL### 25 . 1 to 11 , 2 understand 4 pathophysiology 2 understand 9 in 2 understand 11 , 3 the 4 pathophysiology 4 pathophysiology 5 underlying 5 underlying 8 lesions 6 the 8 lesions 7 vascular 8 lesions 9 in 10 ccm 11 , 16 develop 12 it 13 is 13 is 14 critical 14 critical 15 to 15 to 16 develop 16 develop 21 model 17 a 18 reproducible 17 a 21 model 18 reproducible 19 mouse 19 mouse 21 model 20 genetic 21 model 21 model 22 of 22 of 24 disease 23 this 24 disease here , we report that limited conditional ablation of ccm2 in young adult mice induces observable neurological dysfunction and reproducibly results in brain hemorrhages whose appearance is highly reminiscent of the lesions observed in human ccm patients . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 report 0 ###LEFT-WALL### 33 observed 1 here 2 , 1 here 3 we 3 we 4 report 4 report 8 ablation 4 report 33 observed 5 that 6 limited 6 limited 8 ablation 7 conditional 8 ablation 8 ablation 9 of 8 ablation 19 and 9 of 10 ccm2 10 ccm2 11 in 11 in 14 mice 12 young 13 adult 13 adult 14 mice 15 induces 18 dysfunction 15 induces 19 and 16 observable 18 dysfunction 17 neurological 18 dysfunction 19 and 21 results 19 and 22 in 20 reproducibly 21 results 22 in 23 brain 24 hemorrhages 25 whose 24 hemorrhages 33 observed 25 whose 26 appearance 26 appearance 27 is 27 is 29 reminiscent 28 highly 29 reminiscent 29 reminiscent 30 of 30 of 32 lesions 31 the 32 lesions 33 observed 34 in 33 observed 38 . 34 in 37 patients 35 human 37 patients 36 ccm 37 patients we first demonstrate that conventional or endothelial - specific deletion of ccm2 leads to fatal cardiovascular defects during embryogenesis , including insufficient vascular lumen formation as well as defective arteriogenesis and heart malformation . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 31 and 0 ###LEFT-WALL### 34 . 1 we 31 and 2 first 3 demonstrate 3 demonstrate 6 or 3 demonstrate 28 as 3 demonstrate 31 and 4 that 5 conventional 5 conventional 6 or 6 or 10 deletion 6 or 20 , 6 or 21 including 7 endothelial 8 - 7 endothelial 10 deletion 9 specific 10 deletion 10 deletion 11 of 11 of 13 leads 12 ccm2 13 leads 13 leads 14 to 14 to 17 defects 15 fatal 17 defects 16 cardiovascular 17 defects 17 defects 18 during 18 during 19 embryogenesis 21 including 25 formation 22 insufficient 25 formation 23 vascular 25 formation 24 lumen 25 formation 26 as 27 well 27 well 28 as 28 as 30 arteriogenesis 29 defective 30 arteriogenesis 31 and 32 heart 32 heart 33 malformation these findings confirm [and] [extend] prior studies . 0 ###LEFT-WALL### 2 findings 0 ###LEFT-WALL### 3 confirm 0 ###LEFT-WALL### 8 . 1 these 2 findings 2 findings 3 confirm 3 confirm 7 studies 6 prior 7 studies we then demonstrate that the inducible deletion of ccm2 in adult mice recapitulates the ccm - like brain lesions in humans ; the lesions display disrupted vascular lumens , enlarged capillary cavities , loss of proper neuro - vascular associations and an inflammatory reaction . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 demonstrate 0 ###LEFT-WALL### 22 ; 0 ###LEFT-WALL### 45 . 1 we 3 demonstrate 2 then 3 demonstrate 3 demonstrate 4 that 4 that 7 deletion 4 that 13 recapitulates 5 the 7 deletion 6 inducible 7 deletion 7 deletion 8 of 7 deletion 10 in 7 deletion 13 recapitulates 8 of 9 ccm2 10 in 12 mice 11 adult 12 mice 13 recapitulates 15 ccm 14 the 15 ccm 15 ccm 17 like 16 - 17 like 17 like 19 lesions 17 like 22 ; 18 brain 19 lesions 19 lesions 20 in 20 in 21 humans 22 ; 24 lesions 22 ; 25 display 22 ; 33 , 23 the 24 lesions 24 lesions 25 display 25 display 28 lumens 26 disrupted 28 lumens 27 vascular 28 lumens 28 lumens 32 cavities 29 , 32 cavities 30 enlarged 31 capillary 31 capillary 32 cavities 32 cavities 33 , 33 , 41 and 34 loss 35 of 34 loss 41 and 35 of 40 associations 36 proper 40 associations 37 neuro 38 - 37 neuro 40 associations 39 vascular 40 associations 41 and 44 reaction 42 an 43 inflammatory 42 an 44 reaction 43 inflammatory 44 reaction the ccm lesions also exhibit damaged neuronal architecture , the likely cause of neurologic defects , such as ataxia [and] seizure . 0 ###LEFT-WALL### 3 lesions 0 ###LEFT-WALL### 5 exhibit 0 ###LEFT-WALL### 22 . 1 the 3 lesions 2 ccm 3 lesions 3 lesions 5 exhibit 4 also 5 exhibit 5 exhibit 8 architecture 5 exhibit 18 as 6 damaged 8 architecture 7 neuronal 8 architecture 8 architecture 12 cause 9 , 12 cause 10 the 12 cause 11 likely 12 cause 12 cause 13 of 12 cause 16 , 13 of 15 defects 14 neurologic 15 defects 17 such 18 as 18 as 21 seizure 19 ataxia 21 seizure these mice represent the first ccm2 animal model for ccm and should provide the means to elucidate disease mechanisms and evaluate therapeutic strategies for human ccm . 0 ###LEFT-WALL### 2 mice 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 27 . 1 these 2 mice 2 mice 11 and 3 represent 8 model 3 represent 11 and 4 the 5 first 4 the 8 model 6 ccm2 8 model 7 animal 8 model 8 model 9 for 9 for 10 ccm 11 and 12 should 11 and 16 to 11 and 23 strategies 12 should 13 provide 13 provide 15 means 14 the 15 means 16 to 20 and 17 elucidate 19 mechanisms 17 elucidate 20 and 18 disease 19 mechanisms 20 and 21 evaluate 22 therapeutic 23 strategies 23 strategies 24 for 24 for 26 ccm 25 human 26 ccm [none] hippocampal sclerosis is a relatively common neuropathological finding ( ∼10 [%] of individuals over the age of 85 years ) [characterized] by cell loss and gliosis in the hippocampus that is not explained by alzheimer 's disease . 0 ###LEFT-WALL### 3 sclerosis 0 ###LEFT-WALL### 4 is 0 ###LEFT-WALL### 39 . 2 hippocampal 3 sclerosis 3 sclerosis 4 is 4 is 9 finding 4 is 23 by 4 is 28 in 4 is 35 by 5 a 9 finding 6 relatively 7 common 7 common 9 finding 8 neuropathological 9 finding 9 finding 11 ∼10 10 ( 11 ∼10 11 ∼10 13 of 11 ∼10 21 ) 13 of 14 individuals 14 individuals 15 over 14 individuals 18 of 15 over 17 age 16 the 17 age 18 of 20 years 19 85 20 years 23 by 26 and 24 cell 25 loss 25 loss 26 and 26 and 27 gliosis 28 in 30 hippocampus 29 the 30 hippocampus 30 hippocampus 31 that 30 hippocampus 32 is 31 that 32 is 32 is 33 not 32 is 34 explained 33 not 34 explained 35 by 38 disease 36 alzheimer 37 's 37 's 38 disease hippocampal sclerosis pathology can be associated with different underlying causes , and we refer to hippocampal sclerosis in the aged brain as hippocampal sclerosis associated with ageing . 0 ###LEFT-WALL### 5 be 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 28 . 1 hippocampal 3 pathology 2 sclerosis 3 pathology 3 pathology 4 can 4 can 5 be 5 be 6 associated 6 associated 7 with 7 with 10 causes 8 different 10 causes 9 underlying 10 causes 11 , 12 and 12 and 13 we 12 and 14 refer 13 we 14 refer 14 refer 15 to 14 refer 22 as 14 refer 26 with 15 to 17 sclerosis 16 hippocampal 17 sclerosis 17 sclerosis 18 in 18 in 21 brain 19 the 21 brain 20 aged 21 brain 22 as 24 sclerosis 23 hippocampal 24 sclerosis 24 sclerosis 25 associated 26 with 27 ageing much remains unknown about hippocampal sclerosis associated with ageing . 0 ###LEFT-WALL### 1 much 0 ###LEFT-WALL### 2 remains 0 ###LEFT-WALL### 10 . 1 much 2 remains 2 remains 3 unknown 3 unknown 4 about 4 about 6 sclerosis 5 hippocampal 6 sclerosis 6 sclerosis 7 associated 7 associated 8 with 8 with 9 ageing we combined three different large autopsy cohorts : university of kentucky alzheimer 's disease centre , the nun study and the georgia centenarian study to obtain a pool of 1110 patients , all [of] [whom] were evaluated neuropathologically at the university of kentucky . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 combined 0 ###LEFT-WALL### 8 : 0 ###LEFT-WALL### 32 , 0 ###LEFT-WALL### 44 . 1 we 2 combined 2 combined 7 cohorts 3 three 7 cohorts 4 different 6 autopsy 5 large 6 autopsy 6 autopsy 7 cohorts 8 : 9 university 8 : 13 's 9 university 10 of 9 university 13 's 10 of 12 alzheimer 11 kentucky 12 alzheimer 13 's 20 and 13 's 25 to 14 disease 15 centre 15 centre 16 , 16 , 19 study 16 , 20 and 17 the 19 study 18 nun 19 study 20 and 24 study 21 the 24 study 22 georgia 23 centenarian 23 centenarian 24 study 25 to 32 , 26 obtain 28 pool 26 obtain 32 , 27 a 28 pool 28 pool 29 of 29 of 31 patients 30 1110 31 patients 32 , 36 were 33 all 36 were 36 were 37 evaluated 37 evaluated 38 neuropathologically 37 evaluated 39 at 39 at 41 university 40 the 41 university 41 university 42 of 42 of 43 kentucky we focused on the subset of cases with neuropathology - confirmed hippocampal sclerosis ( n=106 ) . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 focused 0 ###LEFT-WALL### 11 confirmed 1 we 2 focused 2 focused 3 on 2 focused 8 with 3 on 5 subset 4 the 5 subset 5 subset 6 of 6 of 7 cases 8 with 9 neuropathology 10 - 11 confirmed 11 confirmed 13 sclerosis 11 confirmed 17 . 12 hippocampal 13 sclerosis 13 sclerosis 15 n=106 14 ( 15 n=106 15 n=106 16 ) for individuals aged≥95 years at death ( n=179 in our sample ) , each year of life beyond the age of 95 years correlated with increased prevalence of hippocampal sclerosis pathology and decreased prevalence of ['] definite ['] alzheimer 's disease pathology . 0 ###LEFT-WALL### 1 for 0 ###LEFT-WALL### 3 aged≥95 0 ###LEFT-WALL### 43 . 1 for 2 individuals 2 individuals 3 aged≥95 3 aged≥95 4 years 3 aged≥95 25 with 4 years 15 year 4 years 24 correlated 5 at 6 death 5 at 13 , 5 at 15 year 6 death 8 n=179 7 ( 8 n=179 8 n=179 9 in 8 n=179 12 ) 9 in 11 sample 10 our 11 sample 14 each 15 year 15 year 16 of 15 year 24 correlated 16 of 17 life 17 life 18 beyond 17 life 21 of 18 beyond 20 age 19 the 20 age 21 of 23 years 22 95 23 years 25 with 32 and 26 increased 27 prevalence 26 increased 32 and 27 prevalence 28 of 28 of 31 pathology 29 hippocampal 30 sclerosis 30 sclerosis 31 pathology 32 and 33 decreased 32 and 34 prevalence 34 prevalence 35 of 35 of 42 pathology 37 definite 39 alzheimer 39 alzheimer 40 's 40 's 42 pathology 41 disease 42 pathology aberrant tar dna protein 43 immunohistochemistry was seen in 89.9 % of hippocampal sclerosis positive patients compared with 9.7 % of hippocampal sclerosis negative patients . 0 ###LEFT-WALL### 6 immunohistochemistry 0 ###LEFT-WALL### 24 negative 0 ###LEFT-WALL### 26 . 1 aberrant 2 tar 2 tar 6 immunohistochemistry 3 dna 4 protein 4 protein 6 immunohistochemistry 5 43 6 immunohistochemistry 6 immunohistochemistry 7 was 7 was 8 seen 8 seen 9 in 9 in 11 % 10 89.9 11 % 11 % 12 of 11 % 16 patients 11 % 24 negative 12 of 14 sclerosis 13 hippocampal 14 sclerosis 15 positive 16 patients 16 patients 17 compared 16 patients 24 negative 17 compared 18 with 18 with 20 % 19 9.7 20 % 20 % 21 of 21 of 23 sclerosis 22 hippocampal 23 sclerosis 24 negative 25 patients tar dna protein 43 immunohistochemistry can be used to demonstrate that the disease is usually bilateral even when hippocampal sclerosis pathology is not obvious by haematoxylin and eosin stains . 0 ###LEFT-WALL### 27 and 0 ###LEFT-WALL### 30 . 1 tar 2 dna 2 dna 3 protein 3 protein 4 43 3 protein 16 bilateral 3 protein 27 and 5 immunohistochemistry 6 can 6 can 7 be 7 be 8 used 8 used 9 to 8 used 10 demonstrate 9 to 10 demonstrate 10 demonstrate 11 that 11 that 13 disease 11 that 14 is 12 the 13 disease 13 disease 14 is 14 is 15 usually 15 usually 16 bilateral 16 bilateral 17 even 16 bilateral 25 by 17 even 18 when 18 when 21 pathology 18 when 22 is 19 hippocampal 20 sclerosis 20 sclerosis 21 pathology 21 pathology 22 is 22 is 23 not 22 is 24 obvious 23 not 24 obvious 25 by 26 haematoxylin 27 and 29 stains 28 eosin 29 stains tar dna protein 43 immunohistochemistry was negative on brain sections from younger individuals ( n=10 ) after hippocampectomy due to seizures , who had pathologically confirmed hippocampal sclerosis . 0 ###LEFT-WALL### 5 immunohistochemistry 0 ###LEFT-WALL### 7 negative 0 ###LEFT-WALL### 22 , 0 ###LEFT-WALL### 29 . 1 tar 2 dna 2 dna 5 immunohistochemistry 3 protein 5 immunohistochemistry 4 43 5 immunohistochemistry 5 immunohistochemistry 6 was 6 was 7 negative 7 negative 8 on 7 negative 10 sections 8 on 9 brain 10 sections 11 from 10 sections 17 after 10 sections 20 to 11 from 13 individuals 12 younger 13 individuals 13 individuals 15 n=10 14 ( 15 n=10 15 n=10 16 ) 17 after 18 hippocampectomy 19 due 20 to 20 to 21 seizures 22 , 23 who 22 , 24 had 23 who 24 had 24 had 28 sclerosis 25 pathologically 26 confirmed 26 confirmed 28 sclerosis 27 hippocampal 28 sclerosis there was no association between cases with hippocampal sclerosis associated with ageing and apolipoprotein e [genotype] . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 was 0 ###LEFT-WALL### 17 . 1 there 2 was 2 was 4 association 3 no 4 association 4 association 5 between 4 association 10 associated 5 between 6 cases 6 cases 7 with 7 with 9 sclerosis 8 hippocampal 9 sclerosis 10 associated 11 with 11 with 13 and 12 ageing 13 and 13 and 14 apolipoprotein 14 apolipoprotein 15 e age of death and clinical features of hippocampal sclerosis associated with ageing ( [with] or without aberrant tar dna protein 43 ) were distinct from previously published cases of frontotemporal lobar degeneration tar dna protein 43 . 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 23 were 0 ###LEFT-WALL### 37 . 1 age 2 of 1 age 4 and 2 of 3 death 4 and 6 features 4 and 22 ) 4 and 23 were 5 clinical 6 features 6 features 7 of 7 of 9 sclerosis 8 hippocampal 9 sclerosis 9 sclerosis 10 associated 10 associated 15 or 11 with 12 ageing 11 with 15 or 13 ( 15 or 15 or 16 without 16 without 20 protein 17 aberrant 20 protein 18 tar 19 dna 19 dna 20 protein 20 protein 21 43 23 were 24 distinct 24 distinct 25 from 25 from 28 cases 26 previously 27 published 27 published 28 cases 28 cases 29 of 29 of 35 protein 30 frontotemporal 32 degeneration 31 lobar 32 degeneration 32 degeneration 35 protein 33 tar 34 dna 34 dna 35 protein 35 protein 36 43 to help sharpen our ability to discriminate patients with hippocampal sclerosis associated with ageing clinically , the longitudinal cognitive profile of 43 patients with hippocampal sclerosis associated with ageing was compared with the profiles of 75 controls matched for age , gender , education level and apolipoprotein e genotype . 0 ###LEFT-WALL### 20 profile 0 ###LEFT-WALL### 50 . 1 to 2 help 1 to 16 , 1 to 20 profile 2 help 3 sharpen 3 sharpen 5 ability 3 sharpen 6 to 3 sharpen 9 with 4 our 5 ability 6 to 7 discriminate 7 discriminate 8 patients 9 with 11 sclerosis 10 hippocampal 11 sclerosis 11 sclerosis 12 associated 12 associated 13 with 12 associated 15 clinically 13 with 14 ageing 17 the 20 profile 18 longitudinal 20 profile 19 cognitive 20 profile 20 profile 21 of 20 profile 30 was 21 of 23 patients 22 43 23 patients 23 patients 24 with 24 with 26 sclerosis 25 hippocampal 26 sclerosis 26 sclerosis 27 associated 27 associated 28 with 28 with 29 ageing 30 was 31 compared 31 compared 32 with 32 with 34 profiles 33 the 34 profiles 34 profiles 35 of 34 profiles 38 matched 34 profiles 46 and 34 profiles 49 genotype 35 of 37 controls 36 75 37 controls 38 matched 39 for 39 for 40 age 40 age 42 gender 41 , 42 gender 42 gender 43 , 44 education 45 level 45 level 46 and 46 and 47 apolipoprotein 46 and 49 genotype 47 apolipoprotein 48 e these individuals were followed from intake assessment , with 8.2 ( average ) longitudinal cognitive assessments . 0 ###LEFT-WALL### 2 individuals 0 ###LEFT-WALL### 4 followed 1 these 2 individuals 2 individuals 3 were 3 were 4 followed 4 followed 5 from 5 from 7 assessment 6 intake 7 assessment 7 assessment 9 with 8 , 9 with 9 with 10 8.2 9 with 17 . 10 8.2 16 assessments 11 ( 16 assessments 12 average 13 ) 12 average 16 assessments 14 longitudinal 16 assessments 15 cognitive 16 assessments 16 assessments 17 . a neuropsychological profile with relatively high - verbal fluency but low word list recall distinguished the hippocampal sclerosis associated with ageing group at intake ( p<0.015 ) and also 5.5 - 6.5 years before death ( p<0.005 ) . 0 ###LEFT-WALL### 3 profile 0 ###LEFT-WALL### 15 distinguished 0 ###LEFT-WALL### 39 . 1 a 2 neuropsychological 1 a 3 profile 2 neuropsychological 3 profile 3 profile 4 with 3 profile 15 distinguished 4 with 9 fluency 5 relatively 6 high 6 high 7 - 6 high 9 fluency 8 verbal 9 fluency 9 fluency 10 but 10 but 14 recall 11 low 13 list 12 word 13 list 13 list 14 recall 15 distinguished 18 sclerosis 15 distinguished 34 before 16 the 18 sclerosis 17 hippocampal 18 sclerosis 18 sclerosis 19 associated 19 associated 20 with 20 with 21 ageing 20 with 28 and 22 group 23 at 22 group 28 and 23 at 24 intake 24 intake 26 p<0.015 25 ( 26 p<0.015 26 p<0.015 27 ) 28 and 29 also 28 and 33 years 30 5.5 31 - 31 - 32 6.5 31 - 33 years 34 before 35 death 35 death 37 p<0.005 36 ( 37 p<0.005 37 p<0.005 38 ) this may provide a first step in clinical differentiation of hippocampal sclerosis associated with ageing versus pure alzheimer 's disease in their earliest stages . 0 ###LEFT-WALL### 1 this 0 ###LEFT-WALL### 3 provide 0 ###LEFT-WALL### 25 . 1 this 2 may 2 may 3 provide 3 provide 6 step 3 provide 7 in 3 provide 14 with 4 a 6 step 5 first 6 step 7 in 9 differentiation 8 clinical 9 differentiation 9 differentiation 10 of 10 of 12 sclerosis 11 hippocampal 12 sclerosis 12 sclerosis 13 associated 14 with 15 ageing 15 ageing 16 versus 16 versus 20 disease 17 pure 18 alzheimer 18 alzheimer 19 's 19 's 20 disease 20 disease 21 in 21 in 24 stages 22 their 23 earliest 22 their 24 stages in summary , in the largest series of autopsy [-] verified patients with hippocampal sclerosis to date , we characterized the clinical and pathological features associated with hippocampal sclerosis associated with ageing . 0 ###LEFT-WALL### 2 summary 0 ###LEFT-WALL### 3 , 0 ###LEFT-WALL### 33 . 1 in 2 summary 3 , 19 we 3 , 20 characterized 3 , 23 and 4 in 7 series 4 in 18 , 4 in 19 we 5 the 6 largest 5 the 7 series 7 series 8 of 7 series 17 date 8 of 12 patients 9 autopsy 11 verified 11 verified 12 patients 12 patients 13 with 13 with 15 sclerosis 14 hippocampal 15 sclerosis 16 to 17 date 19 we 20 characterized 20 characterized 22 clinical 21 the 22 clinical 23 and 25 features 23 and 26 associated 24 pathological 25 features 25 features 26 associated 26 associated 27 with 26 associated 31 with 27 with 29 sclerosis 28 hippocampal 29 sclerosis 29 sclerosis 30 associated 31 with 32 ageing there is a growing awareness of the need for improved treatment and care of older adults with epilepsy . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 19 . 1 there 2 is 2 is 5 awareness 2 is 9 for 2 is 17 with 3 a 5 awareness 4 growing 5 awareness 5 awareness 6 of 6 of 8 need 7 the 8 need 9 for 12 and 10 improved 11 treatment 11 treatment 12 and 12 and 13 care 12 and 14 of 14 of 16 adults 15 older 16 adults 17 with 18 epilepsy the present review article highlights key clinical and research issues in the emerging field of geriatric epilepsy . 0 ###LEFT-WALL### 5 highlights 0 ###LEFT-WALL### 6 key 0 ###LEFT-WALL### 18 . 1 the 5 highlights 2 present 3 review 3 review 5 highlights 4 article 5 highlights 5 highlights 6 key 6 key 8 and 6 key 11 in 7 clinical 8 and 8 and 10 issues 9 research 10 issues 11 in 14 field 12 the 14 field 13 emerging 14 field 14 field 15 of 15 of 17 epilepsy 16 geriatric 17 epilepsy [drs] ..y martin and schmidt explore the scope of the problems in the field , outline topic areas including cognitive health/dementia , and diagnostic challenges , and also present important research questions that should be considered for the future . 0 ###LEFT-WALL### 2 ..y 0 ###LEFT-WALL### 15 , 0 ###LEFT-WALL### 27 and 0 ###LEFT-WALL### 40 . 2 ..y 4 and 3 martin 4 and 4 and 5 schmidt 4 and 15 , 6 explore 8 scope 6 explore 12 in 6 explore 15 , 7 the 8 scope 8 scope 9 of 9 of 11 problems 10 the 11 problems 12 in 14 field 13 the 14 field 15 , 16 outline 16 outline 18 areas 17 topic 18 areas 18 areas 19 including 19 including 23 and 20 cognitive 21 health/dementia 21 health/dementia 23 and 22 , 23 and 23 and 25 challenges 23 and 26 , 24 diagnostic 25 challenges 26 , 27 and 27 and 28 also 27 and 31 research 27 and 32 questions 29 present 31 research 30 important 31 research 31 research 32 questions 32 questions 33 that 32 questions 36 considered 33 that 34 should 34 should 35 be 35 be 36 considered 36 considered 37 for 37 for 39 future 38 the 39 future as part of this presentation , we will highlight the work of two promising young investigators whose work holds [great] promise for the field of geriatric epilepsy . 0 ###LEFT-WALL### 7 we 0 ###LEFT-WALL### 9 highlight 0 ###LEFT-WALL### 21 promise 0 ###LEFT-WALL### 28 . 1 as 5 presentation 1 as 6 , 1 as 7 we 2 part 3 of 2 part 5 presentation 3 of 5 presentation 4 this 5 presentation 7 we 8 will 8 will 9 highlight 9 highlight 11 work 10 the 11 work 11 work 12 of 11 work 14 promising 12 of 13 two 14 promising 15 young 14 promising 16 investigators 14 promising 21 promise 16 investigators 17 whose 16 investigators 21 promise 17 whose 18 work 18 work 19 holds 21 promise 22 for 22 for 24 field 23 the 24 field 24 field 25 of 25 of 27 epilepsy 26 geriatric 27 epilepsy [dr] ..y roberson will discuss his work focusing on the relationship of epilepsy and cognitive impairment , particularly as it relates to alzheimer 's disease pathology including tau and its role in epileptiform activity . 0 ###LEFT-WALL### 2 ..y 0 ###LEFT-WALL### 5 discuss 0 ###LEFT-WALL### 21 relates 0 ###LEFT-WALL### 35 . 2 ..y 3 roberson 3 roberson 4 will 4 will 5 discuss 5 discuss 7 work 5 discuss 9 on 5 discuss 19 as 6 his 7 work 7 work 8 focusing 9 on 14 and 10 the 11 relationship 11 relationship 12 of 11 relationship 14 and 12 of 13 epilepsy 14 and 16 impairment 15 cognitive 16 impairment 17 , 18 particularly 17 , 19 as 19 as 20 it 19 as 21 relates 20 it 21 relates 21 relates 22 to 22 to 29 and 23 alzheimer 24 's 24 's 26 pathology 25 disease 26 pathology 26 pathology 27 including 26 pathology 29 and 27 including 28 tau 29 and 31 role 29 and 32 in 30 its 31 role 32 in 34 activity 33 epileptiform 34 activity [dr] ..y hope will outline key issues , as well as her work , relating to defining and measuring quality care in geriatric epilepsy . 0 ###LEFT-WALL### 2 ..y 0 ###LEFT-WALL### 5 outline 2 ..y 3 hope 3 hope 4 will 4 will 5 outline 5 outline 7 issues 6 key 7 issues 7 issues 11 as 7 issues 15 relating 8 , 11 as 9 as 10 well 10 well 11 as 11 as 13 work 11 as 14 , 12 her 13 work 14 , 15 relating 15 relating 16 to 15 relating 22 in 15 relating 25 . 16 to 18 and 17 defining 18 and 18 and 21 care 19 measuring 20 quality 20 quality 21 care 22 in 24 epilepsy 23 geriatric 24 epilepsy mucins represent major components of the mucous layer in the stomach , protecting the underlying epithelium from acid , mechanical trauma , proteases and pathogenic bacteria . 0 ###LEFT-WALL### 1 mucins 0 ###LEFT-WALL### 2 represent 0 ###LEFT-WALL### 19 , 0 ###LEFT-WALL### 27 . 1 mucins 2 represent 2 represent 4 components 2 represent 9 in 3 major 4 components 4 components 5 of 5 of 8 layer 6 the 8 layer 7 mucous 8 layer 9 in 11 stomach 10 the 11 stomach 11 stomach 13 protecting 12 , 13 protecting 13 protecting 16 epithelium 13 protecting 17 from 13 protecting 19 , 14 the 16 epithelium 15 underlying 16 epithelium 17 from 18 acid 19 , 24 and 20 mechanical 21 trauma 21 trauma 22 , 22 , 23 proteases 22 , 24 and 24 and 26 bacteria 25 pathogenic 26 bacteria previous studies have shown an association of neoplastic transformation in the stomach with aberrant mucin levels , suggesting a potential role of genetic variation in mucin genes in the development of gastric cancer ( gc ) . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 4 shown 0 ###LEFT-WALL### 37 . 1 previous 2 studies 2 studies 3 have 3 have 4 shown 4 shown 6 association 4 shown 16 levels 5 an 6 association 6 association 7 of 7 of 9 transformation 8 neoplastic 9 transformation 9 transformation 10 in 9 transformation 13 with 10 in 12 stomach 11 the 12 stomach 13 with 15 mucin 14 aberrant 15 mucin 16 levels 18 suggesting 17 , 18 suggesting 18 suggesting 21 role 18 suggesting 25 in 18 suggesting 28 in 18 suggesting 36 ) 19 a 20 potential 19 a 21 role 20 potential 21 role 21 role 22 of 22 of 24 variation 23 genetic 24 variation 25 in 27 genes 26 mucin 27 genes 28 in 30 development 29 the 30 development 30 development 31 of 31 of 33 cancer 32 gastric 33 cancer 33 cancer 35 gc 34 ( 35 gc 35 gc 36 ) we assessed the association of genetic variation in candidate single nucleotide polymorphisms ( snps ) in mucin genes with the risk of chronic atrophic gastritis ( cag ) , a well - established precursor [of] gc in the german population - based esther study . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 assessed 0 ###LEFT-WALL### 45 . 1 we 2 assessed 2 assessed 4 association 2 assessed 42 based 3 the 4 association 4 association 5 of 4 association 8 in 4 association 16 in 4 association 42 based 5 of 7 variation 6 genetic 7 variation 8 in 12 polymorphisms 9 candidate 12 polymorphisms 10 single 11 nucleotide 11 nucleotide 12 polymorphisms 12 polymorphisms 14 snps 13 ( 14 snps 14 snps 15 ) 16 in 18 genes 17 mucin 18 genes 18 genes 19 with 18 genes 22 of 19 with 21 risk 20 the 21 risk 22 of 25 gastritis 23 chronic 25 gastritis 24 atrophic 25 gastritis 25 gastritis 27 cag 25 gastritis 31 well 25 gastritis 36 gc 26 ( 27 cag 27 cag 28 ) 29 , 31 well 30 a 31 well 31 well 32 - 32 - 36 gc 33 established 34 precursor 34 precursor 36 gc 36 gc 37 in 36 gc 41 - 37 in 40 population 38 the 40 population 39 german 40 population 42 based 44 study 43 esther 44 study none of the analysed snps was associated with cag . 0 ###LEFT-WALL### 1 none 0 ###LEFT-WALL### 7 associated 0 ###LEFT-WALL### 10 . 1 none 2 of 1 none 6 was 2 of 5 snps 3 the 5 snps 4 analysed 5 snps 6 was 7 associated 7 associated 8 with 8 with 9 cag however , large studies are needed [to] [disclose] or exclude potential weak associations of these snps with cag risk . 0 ###LEFT-WALL### 4 studies 0 ###LEFT-WALL### 9 or 0 ###LEFT-WALL### 20 . 1 however 2 , 1 however 4 studies 3 large 4 studies 4 studies 5 are 5 are 9 or 6 needed 9 or 9 or 10 exclude 9 or 17 with 9 or 19 risk 10 exclude 13 associations 11 potential 13 associations 12 weak 13 associations 13 associations 14 of 14 of 16 snps 15 these 16 snps 17 with 18 cag medial temporal lobe atrophy ( mta ) is a recognized marker of alzheimer 's disease ( ad ) , however , it can be prominent in frontotemporal lobar degeneration ( ftld ) . 0 ###LEFT-WALL### 4 atrophy 0 ###LEFT-WALL### 8 is 0 ###LEFT-WALL### 19 , 0 ###LEFT-WALL### 33 . 1 medial 3 lobe 2 temporal 3 lobe 3 lobe 4 atrophy 4 atrophy 6 mta 4 atrophy 8 is 5 ( 6 mta 6 mta 7 ) 8 is 11 marker 9 a 11 marker 10 recognized 11 marker 11 marker 12 of 12 of 15 disease 13 alzheimer 14 's 14 's 15 disease 15 disease 17 ad 16 ( 17 ad 17 ad 18 ) 19 , 22 it 19 , 24 be 20 however 21 , 20 however 22 it 22 it 23 can 23 can 24 be 24 be 25 prominent 25 prominent 26 in 26 in 29 degeneration 27 frontotemporal 29 degeneration 28 lobar 29 degeneration 29 degeneration 31 ftld 30 ( 31 ftld 31 ftld 32 ) there is an increasing awareness that posterior atrophy ( pa ) is important in ad and may aid the differentiation of ad from ftld . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 25 . 1 there 2 is 2 is 5 awareness 2 is 23 from 3 an 5 awareness 4 increasing 5 awareness 5 awareness 6 that 6 that 8 atrophy 6 that 16 and 7 posterior 8 atrophy 8 atrophy 10 pa 8 atrophy 16 and 9 ( 10 pa 10 pa 11 ) 12 is 13 important 12 is 16 and 13 important 14 in 14 in 15 ad 16 and 17 may 17 may 18 aid 18 aid 20 differentiation 19 the 20 differentiation 20 differentiation 21 of 21 of 22 ad 23 from 24 ftld visual rating scales are a convenient way of assessing atrophy in a clinical setting . 0 ###LEFT-WALL### 3 scales 0 ###LEFT-WALL### 4 are 0 ###LEFT-WALL### 15 . 1 visual 2 rating 2 rating 3 scales 3 scales 4 are 4 are 7 way 5 a 6 convenient 5 a 7 way 6 convenient 7 way 7 way 8 of 8 of 9 assessing 9 assessing 10 atrophy 9 assessing 11 in 11 in 14 setting 12 a 13 clinical 12 a 14 setting 13 clinical 14 setting in this study , 2 visual rating scales measuring mta and pa were used to compare atrophy patterns in 62 pathologically - confirmed ad and 40 ftld patients . 0 ###LEFT-WALL### 8 scales 0 ###LEFT-WALL### 23 confirmed 0 ###LEFT-WALL### 29 . 1 in 3 study 1 in 4 , 1 in 8 scales 2 this 3 study 5 2 8 scales 6 visual 7 rating 7 rating 8 scales 8 scales 9 measuring 8 scales 13 were 9 measuring 12 pa 10 mta 11 and 11 and 12 pa 13 were 14 used 14 used 15 to 14 used 16 compare 15 to 16 compare 16 compare 18 patterns 16 compare 21 pathologically 17 atrophy 18 patterns 18 patterns 19 in 19 in 20 62 22 - 23 confirmed 23 confirmed 25 and 24 ad 25 and 25 and 28 patients 26 40 28 patients 27 ftld 28 patients anatomical correspondence of mta and pa was assessed using manually - delineated regions of the hippocampus and posterior cingulate gyrus , respectively . 0 ###LEFT-WALL### 2 correspondence 0 ###LEFT-WALL### 7 was 0 ###LEFT-WALL### 11 - 1 anatomical 2 correspondence 2 correspondence 3 of 2 correspondence 7 was 3 of 6 pa 4 mta 5 and 5 and 6 pa 7 was 9 using 7 was 10 manually 8 assessed 9 using 11 - 13 regions 11 - 19 cingulate 12 delineated 13 regions 13 regions 14 of 13 regions 19 cingulate 14 of 17 and 15 the 16 hippocampus 16 hippocampus 17 and 17 and 18 posterior 19 cingulate 20 gyrus 19 cingulate 22 respectively 21 , 22 respectively 22 respectively 23 . both mta and pa scales showed good [inter] - and intrarater reliabilities ( kappa [>] 0.8 ) . 0 ###LEFT-WALL### 5 scales 0 ###LEFT-WALL### 6 showed 0 ###LEFT-WALL### 18 . 1 both 5 scales 2 mta 3 and 3 and 4 pa 4 pa 5 scales 5 scales 6 showed 6 showed 12 reliabilities 7 good 10 and 9 - 10 and 10 and 11 intrarater 10 and 12 reliabilities 12 reliabilities 14 kappa 13 ( 14 kappa 14 kappa 16 0.8 14 kappa 17 ) mta scores showed a good correspondence with manual hippocampal volumes . 0 ###LEFT-WALL### 2 scores 0 ###LEFT-WALL### 3 showed 0 ###LEFT-WALL### 11 . 1 mta 2 scores 2 scores 3 showed 3 showed 6 correspondence 3 showed 7 with 4 a 5 good 4 a 6 correspondence 5 good 6 correspondence 7 with 10 volumes 8 manual 10 volumes 9 hippocampal 10 volumes thirty percent of the ad patients showed pa in the absence of mta . 0 ###LEFT-WALL### 2 percent 0 ###LEFT-WALL### 7 showed 0 ###LEFT-WALL### 14 . 1 thirty 2 percent 2 percent 3 of 2 percent 7 showed 3 of 6 patients 4 the 6 patients 5 ad 6 patients 7 showed 8 pa 7 showed 9 in 9 in 11 absence 10 the 11 absence 11 absence 12 of 12 of 13 mta adding the pa to the mta scale improved discrimination of ad from ftld , and early - onset ad from normal aging . 0 ###LEFT-WALL### 1 adding 0 ###LEFT-WALL### 8 improved 0 ###LEFT-WALL### 23 . 1 adding 3 pa 1 adding 4 to 1 adding 8 improved 2 the 3 pa 4 to 7 scale 5 the 7 scale 6 mta 7 scale 8 improved 9 discrimination 9 discrimination 10 of 10 of 15 and 11 ad 12 from 11 ad 15 and 12 from 13 ftld 14 , 15 and 15 and 19 ad 15 and 20 from 16 early 17 - 16 early 18 onset 18 onset 19 ad 20 from 22 aging 21 normal 22 aging these results underline the importance of considering pa in ad diagnosis , particularly in younger patients where medial temporal atrophy may be less conspicuous . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 underline 1 these 2 results 2 results 3 underline 3 underline 5 importance 4 the 5 importance 5 importance 6 of 5 importance 14 in 6 of 7 considering 7 considering 8 pa 7 considering 11 diagnosis 8 pa 9 in 9 in 10 ad 12 , 13 particularly 12 , 14 in 14 in 16 patients 14 in 25 . 15 younger 16 patients 16 patients 17 where 17 where 20 atrophy 17 where 22 be 18 medial 20 atrophy 19 temporal 20 atrophy 20 atrophy 21 may 21 may 22 be 22 be 24 conspicuous 23 less 24 conspicuous background : although previous studies using [non] - elderly groups have assessed the factorial invariance of the center for epidemiological studies depression scale ( ces - d ) across different groups with the same social - cultural backgrounds , few studies have tested the factorial invariance of the ces - [d] across two elderly groups from countries with different social cultures . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 12 assessed 2 : 10 groups 3 although 6 using 3 although 8 - 3 although 10 groups 4 previous 5 studies 5 studies 6 using 9 elderly 10 groups 10 groups 11 have 11 have 12 assessed 12 assessed 15 invariance 13 the 15 invariance 14 factorial 15 invariance 15 invariance 16 of 16 of 18 center 17 the 18 center 18 center 19 for 18 center 29 across 19 for 23 scale 20 epidemiological 21 studies 21 studies 22 depression 22 depression 23 scale 23 scale 26 - 24 ( 26 - 25 ces 26 - 26 - 27 d 26 - 28 ) 29 across 31 groups 30 different 31 groups 31 groups 32 with 31 groups 41 studies 31 groups 43 tested 32 with 35 social 33 the 34 same 33 the 35 social 35 social 38 backgrounds 36 - 38 backgrounds 37 cultural 38 backgrounds 38 backgrounds 39 , 40 few 41 studies 41 studies 42 have 42 have 43 tested 43 tested 46 invariance 44 the 46 invariance 45 factorial 46 invariance 46 invariance 47 of 47 of 49 ces 48 the 49 ces 49 ces 52 across 50 - 52 across 52 across 55 groups 52 across 62 . 53 two 55 groups 54 elderly 55 groups 55 groups 56 from 56 from 57 countries 57 countries 58 with 58 with 61 cultures 59 different 61 cultures 60 social 61 cultures the purposes of this study were to examine the factorial structure of the ces [-] d , and test its measurement invariance across two different national elderly populations . 0 ###LEFT-WALL### 2 purposes 0 ###LEFT-WALL### 18 and 0 ###LEFT-WALL### 29 . 1 the 2 purposes 2 purposes 3 of 2 purposes 18 and 3 of 5 study 4 this 5 study 6 were 7 to 6 were 8 examine 6 were 18 and 7 to 8 examine 8 examine 11 structure 9 the 11 structure 10 factorial 11 structure 11 structure 12 of 12 of 14 ces 13 the 14 ces 14 ces 16 d 17 , 18 and 18 and 19 test 19 test 22 invariance 19 test 23 across 20 its 22 invariance 21 measurement 22 invariance 23 across 28 populations 24 two 28 populations 25 different 28 populations 26 national 28 populations 27 elderly 28 populations methods : a total of 6806 elderly adults from china ( n = 4903 ) and the netherlands ( n = 1903 ) were included in the final sample . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 16 and 2 : 25 included 2 : 30 . 3 a 4 total 4 total 5 of 4 total 16 and 5 of 8 adults 6 6806 8 adults 7 elderly 8 adults 8 adults 9 from 9 from 10 china 10 china 13 = 11 ( 13 = 12 n 13 = 13 = 14 4903 13 = 15 ) 16 and 18 netherlands 16 and 21 = 16 and 24 were 17 the 18 netherlands 19 ( 21 = 20 n 21 = 21 = 22 1903 21 = 23 ) 24 were 25 included 25 included 26 in 26 in 29 sample 27 the 29 sample 28 final 29 sample the ces [-] d was assessed in both samples . 0 ###LEFT-WALL### 2 ces 0 ###LEFT-WALL### 6 assessed 0 ###LEFT-WALL### 10 . 1 the 2 ces 2 ces 4 d 2 ces 5 was 5 was 6 assessed 6 assessed 7 in 7 in 9 samples 8 both 9 samples three strategies were used in the data analysis procedure . 0 ###LEFT-WALL### 2 strategies 0 ###LEFT-WALL### 4 used 0 ###LEFT-WALL### 10 . 1 three 2 strategies 2 strategies 3 were 3 were 4 used 4 used 5 in 5 in 9 procedure 6 the 9 procedure 7 data 9 procedure 8 analysis 9 procedure first , a confirmatory factor analysis [(] [cfa] [ )(was carried out to determine the factor structures of the ces [-] d that best fitted the two samples . 0 ###LEFT-WALL### 6 analysis 0 ###LEFT-WALL### 11 carried 0 ###LEFT-WALL### 29 . 1 first 2 , 1 first 6 analysis 3 a 4 confirmatory 3 a 6 analysis 4 confirmatory 5 factor 5 factor 6 analysis 6 analysis 10 )(was 10 )(was 11 carried 11 carried 12 out 11 carried 13 to 13 to 14 determine 14 determine 17 structures 15 the 17 structures 16 factor 17 structures 17 structures 18 of 17 structures 23 that 17 structures 25 fitted 18 of 20 ces 19 the 20 ces 20 ces 22 d 23 that 25 fitted 24 best 25 fitted 25 fitted 28 samples 26 the 27 two 27 two 28 samples second , the best fitting model was incorporated into a multi - group [cfa] model to test measurement invariance of the ces [-] d across the two population groups . 0 ###LEFT-WALL### 6 model 0 ###LEFT-WALL### 8 incorporated 0 ###LEFT-WALL### 30 . 1 second 2 , 1 second 6 model 3 the 4 best 3 the 6 model 5 fitting 6 model 6 model 7 was 7 was 8 incorporated 8 incorporated 9 into 8 incorporated 16 to 9 into 15 model 10 a 11 multi 10 a 15 model 11 multi 12 - 11 multi 13 group 13 group 15 model 16 to 19 invariance 17 test 18 measurement 18 measurement 19 invariance 19 invariance 20 of 20 of 22 ces 21 the 22 ces 22 ces 24 d 22 ces 25 across 25 across 29 groups 26 the 27 two 27 two 29 groups 28 population 29 groups third , latent mean differences between the two groups were tested . 0 ###LEFT-WALL### 5 differences 0 ###LEFT-WALL### 11 tested 0 ###LEFT-WALL### 12 . 1 third 2 , 1 third 5 differences 3 latent 5 differences 4 mean 5 differences 5 differences 6 between 5 differences 10 were 6 between 9 groups 7 the 8 two 8 two 9 groups 10 were 11 tested results : the results of confirmatory factor analysis [(] [cfa] [ )(showed : 1 [ )(in both samples , radloff 's four - factor model resulted in a significantly better fit and the four dimensions ( somatic complaints , depressed affect [,] positive [affect] , and interpersonal problems ) of the ces - [d] [seem] to be the most informative in assessing depressive symptoms compared to the single - [,] three - , and the second - order factor models [;] and [2] [ )(the factorial structure [was] invariant across the populations under study . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 4 results 2 : 13 : 3 the 4 results 4 results 5 of 4 results 12 )(showed 5 of 8 analysis 6 confirmatory 8 analysis 7 factor 8 analysis 13 : 14 1 13 : 19 , 14 1 16 )(in 16 )(in 18 samples 17 both 18 samples 19 , 20 radloff 19 , 21 's 19 , 23 - 20 radloff 21 's 21 's 22 four 23 - 25 model 23 - 26 resulted 23 - 32 and 24 factor 25 model 25 model 26 resulted 26 resulted 27 in 27 in 31 fit 28 a 31 fit 29 significantly 30 better 30 better 31 fit 32 and 35 dimensions 32 and 41 affect 33 the 34 four 34 four 35 dimensions 35 dimensions 38 complaints 35 dimensions 40 depressed 35 dimensions 41 affect 36 ( 38 complaints 37 somatic 38 complaints 38 complaints 39 , 39 , 40 depressed 41 affect 46 and 43 positive 46 and 45 , 46 and 46 and 48 problems 46 and 49 ) 46 and 50 of 46 and 56 to 47 interpersonal 48 problems 50 of 52 ces 51 the 52 ces 53 - 56 to 56 to 57 be 57 be 59 most 57 be 60 informative 58 the 59 most 60 informative 61 in 61 in 62 assessing 62 assessing 74 and 63 depressive 64 symptoms 64 symptoms 65 compared 64 symptoms 74 and 65 compared 66 to 66 to 68 single 67 the 68 single 68 single 71 three 69 - 71 three 71 three 72 - 73 , 74 and 74 and 76 second 75 the 76 second 76 second 87 structure 77 - 87 structure 78 order 79 factor 79 factor 80 models 80 models 82 and 82 and 86 factorial 82 and 87 structure 85 )(the 86 factorial 87 structure 89 invariant 87 structure 93 under 87 structure 95 . 89 invariant 90 across 90 across 92 populations 91 the 92 populations 93 under 94 study however , only partial scalar and uniqueness invariance of the ces [-] d items was supported . 0 ###LEFT-WALL### 3 only 0 ###LEFT-WALL### 16 supported 0 ###LEFT-WALL### 17 . 1 however 2 , 1 however 3 only 3 only 8 invariance 4 partial 8 invariance 5 scalar 6 and 6 and 7 uniqueness 6 and 8 invariance 8 invariance 9 of 8 invariance 15 was 9 of 14 items 10 the 14 items 11 ces 13 d 11 ces 14 items 15 was 16 supported latent means in the partial invariant model were lower for the dutch sample , compared to the chinese sample . 0 ###LEFT-WALL### 2 means 0 ###LEFT-WALL### 14 , 0 ###LEFT-WALL### 20 . 1 latent 2 means 2 means 3 in 2 means 14 , 3 in 7 model 4 the 7 model 5 partial 7 model 6 invariant 7 model 8 were 9 lower 8 were 14 , 9 lower 10 for 10 for 13 sample 11 the 13 sample 12 dutch 13 sample 14 , 15 compared 14 , 16 to 16 to 19 sample 17 the 19 sample 18 chinese 19 sample conclusions : our findings provide evidence of a valid factorial structure of the ces [-] d that could be applied to elderly populations from both china and the netherlands , producing a meaningful comparison of total scores between the two elderly groups . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 4 findings 2 : 5 provide 3 our 4 findings 4 findings 5 provide 5 provide 6 evidence 5 provide 21 to 5 provide 31 producing 6 evidence 7 of 6 evidence 17 that 6 evidence 18 could 7 of 11 structure 8 a 11 structure 9 valid 11 structure 10 factorial 11 structure 11 structure 12 of 12 of 14 ces 13 the 14 ces 14 ces 16 d 17 that 18 could 18 could 19 be 19 be 20 applied 21 to 27 and 22 elderly 23 populations 23 populations 24 from 23 populations 27 and 24 from 26 china 25 both 26 china 27 and 29 netherlands 28 the 29 netherlands 30 , 31 producing 31 producing 34 comparison 31 producing 43 . 32 a 33 meaningful 32 a 34 comparison 33 meaningful 34 comparison 34 comparison 35 of 35 of 37 scores 36 total 37 scores 37 scores 38 between 38 between 42 groups 39 the 42 groups 40 two 42 groups 41 elderly 42 groups however , for some specific factors and items , caution is required when comparing the depressive symptoms between chinese and dutch elderly groups . 0 ###LEFT-WALL### 10 caution 0 ###LEFT-WALL### 12 required 0 ###LEFT-WALL### 24 . 1 however 2 , 1 however 10 caution 3 for 7 and 3 for 9 , 3 for 10 caution 4 some 6 factors 5 specific 6 factors 6 factors 7 and 7 and 8 items 10 caution 11 is 11 is 12 required 12 required 13 when 13 when 14 comparing 14 comparing 17 symptoms 14 comparing 18 between 15 the 17 symptoms 16 depressive 17 symptoms 18 between 20 and 19 chinese 20 and 20 and 23 groups 21 dutch 23 groups 22 elderly 23 groups background : peroxisome proliferator - activated receptor - [γ] co - activator [(] pgc ) - 1α is a transcriptional co - activator of antioxidant genes and a master regulator of mitochondrial biogenesis . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 34 . 2 : 4 proliferator 2 : 5 - 2 : 8 - 3 peroxisome 4 proliferator 5 - 7 receptor 6 activated 7 receptor 8 - 17 1α 8 - 18 is 10 co 14 pgc 10 co 16 - 10 co 17 1α 11 - 14 pgc 12 activator 14 pgc 14 pgc 15 ) 17 1α 18 is 18 is 23 activator 19 a 23 activator 20 transcriptional 23 activator 21 co 22 - 21 co 23 activator 23 activator 24 of 24 of 27 and 25 antioxidant 26 genes 26 genes 27 and 27 and 30 regulator 27 and 31 of 28 a 30 regulator 29 master 30 regulator 31 of 33 biogenesis 32 mitochondrial 33 biogenesis parkinson 's disease ( pd ) is associated with oxidative stress and mitochondrial dysfunction and recent work suggests a role for pgc - 1α . 0 ###LEFT-WALL### 3 disease 0 ###LEFT-WALL### 15 and 1 parkinson 2 's 2 's 3 disease 3 disease 5 pd 3 disease 7 is 4 ( 5 pd 5 pd 6 ) 7 is 8 associated 8 associated 9 with 9 with 12 and 10 oxidative 11 stress 11 stress 12 and 12 and 14 dysfunction 13 mitochondrial 14 dysfunction 15 and 17 work 15 and 18 suggests 16 recent 17 work 17 work 18 suggests 18 suggests 20 role 19 a 20 role 20 role 21 for 20 role 24 1α 21 for 22 pgc 23 - 24 1α 24 1α 25 . we hypothesized that the rs8192678 [pgc] - 1α single nucleotide polymorphism ( snp ) may influence risk or age of onset [of] pd . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 hypothesized 0 ###LEFT-WALL### 24 . 1 we 2 hypothesized 2 hypothesized 3 that 3 that 11 polymorphism 3 that 16 influence 4 the 11 polymorphism 5 rs8192678 7 - 5 rs8192678 8 1α 8 1α 11 polymorphism 9 single 10 nucleotide 10 nucleotide 11 polymorphism 11 polymorphism 13 snp 11 polymorphism 15 may 12 ( 13 snp 13 snp 14 ) 15 may 16 influence 16 influence 18 or 17 risk 18 or 18 or 19 age 18 or 20 of 20 of 23 pd 21 onset 23 pd the a10398g mitochondrial snp has been inversely associated with risk of pd in some studies . 0 ###LEFT-WALL### 2 a10398g 0 ###LEFT-WALL### 8 associated 0 ###LEFT-WALL### 16 . 1 the 2 a10398g 2 a10398g 4 snp 2 a10398g 6 been 2 a10398g 8 associated 3 mitochondrial 4 snp 4 snp 5 has 5 has 6 been 7 inversely 8 associated 8 associated 9 with 8 associated 13 in 9 with 10 risk 10 risk 11 of 11 of 12 pd 13 in 15 studies 14 some 15 studies in the current study we analyzed whether rs8192678 or other pgc - 1α snps affect pd risk or age [of] onset , [singularly] or [in] association with the a10398g snp . 0 ###LEFT-WALL### 5 we 0 ###LEFT-WALL### 6 analyzed 0 ###LEFT-WALL### 31 . 1 in 4 study 1 in 5 we 2 the 4 study 3 current 4 study 5 we 6 analyzed 6 analyzed 7 whether 6 analyzed 14 snps 6 analyzed 15 affect 7 whether 9 or 7 whether 13 1α 8 rs8192678 9 or 9 or 11 pgc 9 or 12 - 9 or 13 1α 10 other 11 pgc 14 snps 15 affect 15 affect 24 or 15 affect 27 with 16 pd 17 risk 17 risk 18 or 18 or 21 onset 18 or 24 or 19 age 21 onset 22 , 24 or 24 or 26 association 27 with 30 snp 28 the 30 snp 29 a10398g 30 snp methods : genomic dna samples from 378 pd patients and 173 age - matched controls were analyzed by multiplexed probe sequencing , followed by statistical analyses of the association of each snp , alone or [in] combination , with risk or age of onset [of] pd . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 47 . 2 : 41 or 3 genomic 4 dna 4 dna 5 samples 5 samples 6 from 5 samples 10 and 6 from 9 patients 7 378 9 patients 8 pd 9 patients 10 and 12 age 10 and 13 - 10 and 14 matched 10 and 15 controls 10 and 16 were 10 and 17 analyzed 10 and 35 or 11 173 12 age 15 controls 16 were 17 analyzed 18 by 17 analyzed 23 followed 17 analyzed 34 alone 18 by 21 sequencing 19 multiplexed 20 probe 20 probe 21 sequencing 22 , 23 followed 23 followed 24 by 23 followed 33 , 24 by 26 analyses 25 statistical 26 analyses 26 analyses 27 of 26 analyses 30 of 27 of 29 association 28 the 29 association 30 of 32 snp 31 each 32 snp 35 or 37 combination 35 or 38 , 35 or 39 with 35 or 41 or 39 with 40 risk 41 or 42 age 41 or 43 of 43 of 46 pd 44 onset 46 pd adjustments were made for age of [onset] being less than the age of sampling , and for the observed dependence between these two ages . 0 ###LEFT-WALL### 1 adjustments 0 ###LEFT-WALL### 3 made 0 ###LEFT-WALL### 25 . 1 adjustments 2 were 2 were 3 made 3 made 16 and 4 for 5 age 4 for 16 and 5 age 6 of 5 age 13 of 6 of 8 being 8 being 9 less 8 being 10 than 10 than 12 age 11 the 12 age 13 of 14 sampling 15 , 16 and 16 and 17 for 17 for 20 dependence 18 the 20 dependence 19 observed 20 dependence 20 dependence 21 between 21 between 24 ages 22 these 23 two 23 two 24 ages the pd samples were obtained as two separate cohorts , therefore statistical methods accounted for different sampling methods between the two cohorts , and data were analyzed using cox regression adjusted for sampling in the risk set definition and in the model . 0 ###LEFT-WALL### 3 samples 0 ###LEFT-WALL### 5 obtained 0 ###LEFT-WALL### 15 for 0 ###LEFT-WALL### 24 and 0 ###LEFT-WALL### 43 . 1 the 3 samples 2 pd 3 samples 3 samples 4 were 4 were 5 obtained 5 obtained 6 as 6 as 7 two 6 as 8 separate 7 two 8 separate 8 separate 9 cohorts 8 separate 11 therefore 10 , 11 therefore 11 therefore 13 methods 12 statistical 13 methods 13 methods 15 for 14 accounted 15 for 15 for 18 methods 15 for 19 between 16 different 18 methods 17 sampling 18 methods 19 between 22 cohorts 20 the 21 two 21 two 22 cohorts 23 , 24 and 24 and 25 data 24 and 33 sampling 25 data 26 were 26 were 27 analyzed 27 analyzed 28 using 28 using 29 cox 29 cox 30 regression 29 cox 33 sampling 30 regression 31 adjusted 31 adjusted 32 for 32 for 33 sampling 33 sampling 39 and 34 in 38 definition 34 in 39 and 35 the 38 definition 36 risk 37 set 37 set 38 definition 39 and 40 in 40 in 42 model 41 the 42 model results : the rs8192678 pgc - 1α snp was not associated with the risk of pd . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 17 . 2 : 5 pgc 2 : 6 - 3 the 5 pgc 4 rs8192678 5 pgc 6 - 7 1α 7 1α 8 snp 7 1α 9 was 8 snp 9 was 9 was 10 not 9 was 12 with 10 not 11 associated 12 with 14 risk 13 the 14 risk 14 risk 15 of 15 of 16 pd however , an association of the pgc [-] 1α rs8192678 gg variant with longevity was seen in control subjects ( p=0.019 ) . 0 ###LEFT-WALL### 4 association 0 ###LEFT-WALL### 16 seen 0 ###LEFT-WALL### 23 . 1 however 2 , 1 however 4 association 3 an 4 association 4 association 5 of 4 association 12 variant 4 association 15 was 5 of 11 gg 6 the 10 rs8192678 7 pgc 9 1α 9 1α 10 rs8192678 10 rs8192678 11 gg 12 variant 13 with 13 with 14 longevity 15 was 16 seen 16 seen 17 in 17 in 19 subjects 18 control 19 subjects 19 subjects 21 p=0.019 20 ( 21 p=0.019 21 p=0.019 22 ) exploratory studies indicated that the [cc] variant of rs6821591 was associated with risk of early onset pd ( p=0.029 ) , with pd age of onset [(] p=0.047 ) , [and] with longevity ( p=0.022 ) . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 3 indicated 0 ###LEFT-WALL### 37 . 1 exploratory 2 studies 2 studies 3 indicated 3 indicated 4 that 4 that 7 variant 4 that 11 associated 5 the 7 variant 7 variant 8 of 7 variant 10 was 8 of 9 rs6821591 10 was 11 associated 11 associated 12 with 12 with 13 risk 13 risk 14 of 14 of 17 pd 15 early 16 onset 16 onset 17 pd 17 pd 19 p=0.029 17 pd 22 with 17 pd 32 with 18 ( 19 p=0.029 19 p=0.029 20 ) 21 , 22 with 22 with 24 age 22 with 29 ) 23 pd 24 age 24 age 25 of 25 of 28 p=0.047 26 onset 28 p=0.047 30 , 32 with 32 with 33 longevity 32 with 36 ) 33 longevity 35 p=0.022 34 ( 35 p=0.022 35 p=0.022 36 ) the rs2970848 gg allele was associated with risk of late onset pd ( p=0.027 ) . 0 ###LEFT-WALL### 4 allele 0 ###LEFT-WALL### 6 associated 0 ###LEFT-WALL### 16 . 1 the 4 allele 2 rs2970848 4 allele 3 gg 4 allele 4 allele 5 was 5 was 6 associated 6 associated 7 with 7 with 8 risk 8 risk 9 of 9 of 12 pd 10 late 11 onset 11 onset 12 pd 12 pd 14 p=0.027 13 ( 14 p=0.027 14 p=0.027 15 ) conclusions : these data reveal possible associations of the pgc - 1α snps rs6821591 and rs2970848 with risk or age of onset [of] pd , [and] of the pgc - 1α rs8192678 gg and the rs6821591 [cc] variants with longevity . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 41 . 2 : 4 data 2 : 5 reveal 2 : 11 - 2 : 30 - 3 these 4 data 4 data 5 reveal 5 reveal 7 associations 6 possible 7 associations 7 associations 8 of 8 of 10 pgc 9 the 10 pgc 11 - 19 or 12 1α 14 rs6821591 13 snps 14 rs6821591 14 rs6821591 15 and 15 and 16 rs2970848 15 and 17 with 15 and 19 or 17 with 18 risk 19 or 20 age 19 or 27 of 20 age 21 of 21 of 24 pd 22 onset 24 pd 25 , 27 of 27 of 29 pgc 27 of 30 - 28 the 29 pgc 30 - 34 and 31 1α 33 gg 32 rs8192678 33 gg 33 gg 34 and 34 and 38 variants 34 and 39 with 35 the 38 variants 36 rs6821591 38 variants 39 with 40 longevity if replicated in other datasets , these findings may have important implications regarding the role of pgc - 1α in pd and longevity . 0 ###LEFT-WALL### 8 findings 0 ###LEFT-WALL### 10 have 0 ###LEFT-WALL### 18 - 0 ###LEFT-WALL### 19 1α 0 ###LEFT-WALL### 24 . 1 if 2 replicated 1 if 6 , 1 if 8 findings 2 replicated 3 in 3 in 5 datasets 4 other 5 datasets 7 these 8 findings 8 findings 9 may 9 may 10 have 10 have 12 implications 11 important 12 implications 12 implications 13 regarding 12 implications 16 of 13 regarding 15 role 14 the 15 role 16 of 17 pgc 18 - 19 1α 19 1α 20 in 20 in 22 and 21 pd 22 and 22 and 23 longevity the oropharyngeal swallow involves a rapid , highly coordinated set of neuromuscular actions beginning with lip closure and terminating with opening of the upper esophageal sphincter . 0 ###LEFT-WALL### 3 swallow 0 ###LEFT-WALL### 4 involves 0 ###LEFT-WALL### 27 . 1 the 3 swallow 2 oropharyngeal 3 swallow 3 swallow 4 involves 4 involves 10 set 5 a 10 set 6 rapid 7 , 6 rapid 10 set 8 highly 9 coordinated 9 coordinated 10 set 10 set 11 of 10 set 14 beginning 11 of 13 actions 12 neuromuscular 13 actions 14 beginning 15 with 15 with 18 and 16 lip 17 closure 17 closure 18 and 18 and 19 terminating 18 and 20 with 18 and 22 of 20 with 21 opening 22 of 26 sphincter 23 the 26 sphincter 24 upper 26 sphincter 25 esophageal 26 sphincter evaluation of the oropharyngeal swallow usually involves the use of a modified barium swallow radiographic study with the goals of [(] [i] [ )(defining the patient 's swallow anatomy and physiology causing the dysphagia [;] and [(] ii ) evaluating the immediate effectiveness of treatment procedures including selected postures , sensory enhancement , swallow maneuvers , and diet changes . 0 ###LEFT-WALL### 1 evaluation 0 ###LEFT-WALL### 7 involves 1 evaluation 2 of 1 evaluation 7 involves 2 of 5 swallow 3 the 5 swallow 4 oropharyngeal 5 swallow 6 usually 7 involves 7 involves 9 use 8 the 9 use 9 use 10 of 9 use 17 with 10 of 16 study 11 a 16 study 12 modified 13 barium 13 barium 16 study 14 swallow 16 study 15 radiographic 16 study 17 with 19 goals 18 the 19 goals 19 goals 20 of 20 of 24 )(defining 24 )(defining 36 and 25 the 26 patient 26 patient 27 's 27 's 29 anatomy 28 swallow 29 anatomy 29 anatomy 30 and 30 and 31 physiology 30 and 36 and 31 physiology 32 causing 32 causing 34 dysphagia 33 the 34 dysphagia 36 and 38 ii 36 and 39 ) 36 and 40 evaluating 36 and 44 of 36 and 47 including 40 evaluating 43 effectiveness 41 the 43 effectiveness 42 immediate 43 effectiveness 44 of 46 procedures 45 treatment 46 procedures 47 including 57 and 48 selected 49 postures 49 postures 50 , 50 , 52 enhancement 50 , 53 , 51 sensory 52 enhancement 53 , 55 maneuvers 53 , 57 and 54 swallow 55 maneuvers 56 , 57 and 57 and 59 changes 57 and 60 . 58 diet 59 changes exercise programs may be helpful , but their immediate effects cannot be examined during the initial modified barium swallow . 0 ###LEFT-WALL### 2 programs 0 ###LEFT-WALL### 4 be 0 ###LEFT-WALL### 7 but 0 ###LEFT-WALL### 20 . 1 exercise 2 programs 2 programs 3 may 3 may 4 be 4 be 5 helpful 6 , 7 but 7 but 10 effects 7 but 13 examined 8 their 10 effects 9 immediate 10 effects 10 effects 11 cannot 11 cannot 12 be 12 be 13 examined 13 examined 14 during 14 during 19 swallow 15 the 19 swallow 16 initial 17 modified 17 modified 18 barium 18 barium 19 swallow exercise programs can be evaluated on a second radiographic study 3 - 4 weeks later . 0 ###LEFT-WALL### 2 programs 0 ###LEFT-WALL### 5 evaluated 0 ###LEFT-WALL### 16 . 1 exercise 2 programs 2 programs 3 can 3 can 4 be 4 be 5 evaluated 5 evaluated 6 on 5 evaluated 15 later 6 on 10 study 7 a 10 study 8 second 10 study 9 radiographic 10 study 11 3 12 - 12 - 13 4 12 - 14 weeks 14 weeks 15 later the resultant report should include all of this information . 0 ###LEFT-WALL### 3 report 0 ###LEFT-WALL### 5 include 0 ###LEFT-WALL### 10 . 1 the 3 report 2 resultant 3 report 3 report 4 should 4 should 5 include 5 include 9 information 6 all 7 of 6 all 9 information 7 of 9 information 8 this 9 information the speech [-] language pathologist is usually the professional most involved in the evaluation and treatment . 0 ###LEFT-WALL### 5 pathologist 0 ###LEFT-WALL### 6 is 0 ###LEFT-WALL### 17 . 1 the 5 pathologist 2 speech 5 pathologist 4 language 5 pathologist 5 pathologist 6 is 6 is 7 usually 6 is 9 professional 6 is 12 in 8 the 9 professional 9 professional 11 involved 10 most 11 involved 12 in 15 and 13 the 14 evaluation 14 evaluation 15 and 15 and 16 treatment medications and surgery have a very limited role in the treatment of oropharyngeal dysphagia . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 4 have 0 ###LEFT-WALL### 15 . 1 medications 2 and 2 and 3 surgery 2 and 4 have 4 have 8 role 4 have 9 in 5 a 6 very 5 a 8 role 6 very 7 limited 7 limited 8 role 9 in 11 treatment 10 the 11 treatment 11 treatment 12 of 12 of 14 dysphagia 13 oropharyngeal 14 dysphagia given an australian national and state policy agenda that continues to promote collaborative work , many community organisations are attempting to engage [in] partnerships with mixed results . 0 ###LEFT-WALL### 18 organisations 0 ###LEFT-WALL### 19 are 0 ###LEFT-WALL### 28 . 1 given 5 and 1 given 15 , 1 given 18 organisations 2 an 4 national 3 australian 4 national 4 national 5 and 5 and 8 agenda 5 and 9 that 5 and 10 continues 6 state 8 agenda 7 policy 8 agenda 9 that 10 continues 10 continues 11 to 10 continues 12 promote 11 to 12 promote 12 promote 14 work 13 collaborative 14 work 16 many 18 organisations 17 community 18 organisations 18 organisations 19 are 19 are 20 attempting 20 attempting 21 to 20 attempting 22 engage 21 to 22 engage 22 engage 24 partnerships 24 partnerships 25 with 25 with 27 results 26 mixed 27 results this paper reports on a qualitative study conducted to explore the experiences of existing partnerships between organisations and small community groups who deliver community based support services to older people from culturally diverse backgrounds . 0 ###LEFT-WALL### 2 paper 0 ###LEFT-WALL### 3 reports 0 ###LEFT-WALL### 35 . 1 this 2 paper 2 paper 3 reports 3 reports 4 on 3 reports 24 community 3 reports 25 based 4 on 7 study 5 a 7 study 6 qualitative 7 study 7 study 8 conducted 8 conducted 9 to 9 to 10 explore 11 the 24 community 12 experiences 13 of 12 experiences 18 and 13 of 15 partnerships 14 existing 15 partnerships 15 partnerships 16 between 16 between 17 organisations 18 and 21 groups 18 and 22 who 18 and 23 deliver 18 and 24 community 19 small 20 community 20 community 21 groups 22 who 23 deliver 24 community 25 based 25 based 27 services 25 based 31 from 26 support 27 services 27 services 28 to 28 to 30 people 29 older 30 people 31 from 34 backgrounds 32 culturally 33 diverse 33 diverse 34 backgrounds in particular , this study sought to identify the key factors [that] facilitate and hinder the formation , maintenance and effectiveness of partnerships within the ethnic and multicultural community aged care ( emcac ) sector . 0 ###LEFT-WALL### 5 study 0 ###LEFT-WALL### 6 sought 0 ###LEFT-WALL### 36 . 1 in 2 particular 2 particular 3 , 2 particular 5 study 4 this 5 study 5 study 6 sought 6 sought 7 to 6 sought 14 and 7 to 14 and 8 identify 10 key 8 identify 14 and 9 the 10 key 10 key 11 factors 10 key 13 facilitate 11 factors 13 facilitate 14 and 15 hinder 15 hinder 20 and 15 hinder 24 within 16 the 20 and 17 formation 18 , 18 , 19 maintenance 18 , 20 and 20 and 21 effectiveness 20 and 22 of 22 of 23 partnerships 24 within 35 sector 25 the 35 sector 26 ethnic 27 and 27 and 31 care 27 and 33 emcac 27 and 35 sector 28 multicultural 29 community 29 community 30 aged 30 aged 31 care 32 ( 33 emcac 33 emcac 34 ) fourteen participants representing nine community and health service organisations located in the melbourne metropolitan area took part in semi - structured interviews . 0 ###LEFT-WALL### 5 community 0 ###LEFT-WALL### 6 and 0 ###LEFT-WALL### 23 . 1 fourteen 2 participants 2 participants 5 community 3 representing 5 community 4 nine 5 community 6 and 9 organisations 6 and 17 part 7 health 9 organisations 8 service 9 organisations 9 organisations 10 located 9 organisations 17 part 10 located 11 in 11 in 13 melbourne 12 the 13 melbourne 13 melbourne 15 area 13 melbourne 16 took 14 metropolitan 15 area 15 area 16 took 17 part 18 in 18 in 22 interviews 19 semi 20 - 19 semi 22 interviews 21 structured 22 interviews participants reported that partnerships between organisations are necessary and beneficial within the emcac sector . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 2 reported 0 ###LEFT-WALL### 15 . 1 participants 2 reported 2 reported 3 that 3 that 4 partnerships 3 that 7 are 4 partnerships 5 between 4 partnerships 7 are 5 between 6 organisations 7 are 9 and 8 necessary 9 and 9 and 10 beneficial 10 beneficial 11 within 11 within 14 sector 12 the 14 sector 13 emcac 14 sector organisational capacity , access to information and guidelines , and the inequality experienced by smaller organisations were key issues identified by participants . 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 18 key 0 ###LEFT-WALL### 23 . 1 organisational 2 capacity 2 capacity 3 , 3 , 4 access 3 , 7 and 4 access 5 to 5 to 6 information 7 and 8 guidelines 7 and 10 and 9 , 10 and 10 and 12 inequality 10 and 13 experienced 10 and 17 were 11 the 12 inequality 13 experienced 14 by 14 by 16 organisations 15 smaller 16 organisations 17 were 18 key 18 key 19 issues 19 issues 20 identified 20 identified 21 by 21 by 22 participants increasing organisational capacity and reducing the inequalities experienced in partnerships may be addressed via training and education about the nature of partnerships , as well as by advocating for increased resources to smaller ethno - specific organisations . 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 13 addressed 0 ###LEFT-WALL### 35 - 0 ###LEFT-WALL### 38 . 1 increasing 3 capacity 2 organisational 3 capacity 3 capacity 4 and 4 and 5 reducing 4 and 7 inequalities 4 and 8 experienced 4 and 11 may 6 the 7 inequalities 7 inequalities 8 experienced 8 experienced 9 in 9 in 10 partnerships 11 may 12 be 12 be 13 addressed 13 addressed 14 via 13 addressed 18 about 14 via 16 and 15 training 16 and 16 and 17 education 18 about 20 nature 19 the 20 nature 20 nature 21 of 21 of 22 partnerships 22 partnerships 24 as 23 , 24 as 24 as 25 well 24 as 35 - 25 well 26 as 25 well 29 for 26 as 27 by 27 by 28 advocating 29 for 31 resources 30 increased 31 resources 31 resources 32 to 32 to 34 ethno 33 smaller 34 ethno 35 - 37 organisations 36 specific 37 organisations further investigation is required to examine whether [not] engaging in partnerships will deem an organisation unsustainable in the longer term . 0 ###LEFT-WALL### 2 investigation 0 ###LEFT-WALL### 4 required 0 ###LEFT-WALL### 21 . 1 further 2 investigation 2 investigation 3 is 3 is 4 required 4 required 5 to 4 required 6 examine 5 to 6 examine 6 examine 7 whether 7 whether 9 engaging 7 whether 13 deem 9 engaging 10 in 9 engaging 12 will 10 in 11 partnerships 12 will 13 deem 13 deem 15 organisation 14 an 15 organisation 15 organisation 16 unsustainable 16 unsustainable 17 in 17 in 20 term 18 the 20 term 19 longer 20 term background : recent evidence indicates that a lower plasma level of 25 - hydroxyvitamin d ( 25 ohd ) is associated with a higher risk of the metabolic syndrome . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 4 evidence 2 : 5 indicates 2 : 30 . 3 recent 4 evidence 4 evidence 5 indicates 5 indicates 6 that 6 that 10 level 6 that 21 associated 7 a 10 level 8 lower 9 plasma 9 plasma 10 level 10 level 11 of 10 level 20 is 11 of 12 25 12 25 14 hydroxyvitamin 13 - 14 hydroxyvitamin 14 hydroxyvitamin 15 d 14 hydroxyvitamin 18 ohd 14 hydroxyvitamin 19 ) 16 ( 18 ohd 17 25 18 ohd 18 ohd 19 ) 20 is 21 associated 21 associated 22 with 22 with 25 risk 23 a 25 risk 24 higher 25 risk 25 risk 26 of 26 of 29 syndrome 27 the 29 syndrome 28 metabolic 29 syndrome it has not been studied in older people with a high prevalence of vitamin d insufficiency . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 5 studied 0 ###LEFT-WALL### 17 . 1 it 2 has 2 has 3 not 2 has 4 been 4 been 5 studied 5 studied 6 in 5 studied 9 with 6 in 8 people 7 older 8 people 9 with 12 prevalence 10 a 11 high 10 a 12 prevalence 11 high 12 prevalence 12 prevalence 13 of 13 of 16 insufficiency 14 vitamin 15 d 14 vitamin 16 insufficiency objective : this study investigates the association between vitamin d status and the metabolic syndrome in community [-] dwelling older persons in the netherlands . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 25 . 2 : 4 study 2 : 5 investigates 3 this 4 study 4 study 5 investigates 5 investigates 7 association 5 investigates 8 between 6 the 7 association 8 between 12 and 9 vitamin 10 d 9 vitamin 11 status 11 status 12 and 12 and 15 syndrome 12 and 16 in 12 and 22 in 13 the 15 syndrome 14 metabolic 15 syndrome 16 in 21 persons 17 community 19 dwelling 19 dwelling 21 persons 20 older 21 persons 22 in 24 netherlands 23 the 24 netherlands design and patients : the study is part of the longitudinal aging study amsterdam , an ongoing cohort study in a representative sample of dutch older persons . 0 ###LEFT-WALL### 3 patients 0 ###LEFT-WALL### 4 : 1 design 2 and 2 and 3 patients 4 : 6 study 4 : 7 is 5 the 6 study 6 study 7 is 7 is 8 part 8 part 9 of 9 of 14 amsterdam 10 the 14 amsterdam 11 longitudinal 12 aging 12 aging 13 study 13 study 14 amsterdam 14 amsterdam 19 study 15 , 19 study 16 an 17 ongoing 16 an 19 study 17 ongoing 18 cohort 18 cohort 19 study 19 study 20 in 19 study 24 of 19 study 28 . 20 in 23 sample 21 a 22 representative 21 a 23 sample 22 representative 23 sample 24 of 27 persons 25 dutch 27 persons 26 older 27 persons a total of 1286 subjects ( 629 men and 657 women ) between the ages of 65 and 88 years participated in the study . 0 ###LEFT-WALL### 2 total 0 ###LEFT-WALL### 21 participated 0 ###LEFT-WALL### 25 . 1 a 2 total 2 total 3 of 2 total 13 between 2 total 21 participated 3 of 5 subjects 4 1286 5 subjects 5 subjects 9 and 6 ( 9 and 7 629 8 men 8 men 9 and 9 and 11 women 9 and 12 ) 10 657 11 women 13 between 15 ages 14 the 15 ages 15 ages 16 of 16 of 20 years 17 65 18 and 18 and 19 88 18 and 20 years 21 participated 22 in 22 in 24 study 23 the 24 study measurements : metabolic [syndrome] ( u.s [.] national cholesterol education program definition ) and its individual components were assessed as well as serum 25 ohd levels . 0 ###LEFT-WALL### 1 measurements 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 14 and 0 ###LEFT-WALL### 27 . 1 measurements 2 : 2 : 3 metabolic 3 metabolic 12 definition 5 ( 12 definition 6 u.s 8 national 8 national 12 definition 9 cholesterol 10 education 10 education 11 program 11 program 12 definition 12 definition 13 ) 14 and 16 individual 14 and 19 assessed 15 its 16 individual 16 individual 17 components 16 individual 18 were 16 individual 19 assessed 17 components 18 were 19 assessed 21 well 19 assessed 25 ohd 19 assessed 26 levels 20 as 21 well 22 as 23 serum 22 as 25 ohd 23 serum 24 25 25 ohd 26 levels results : among the participants , the prevalence of the metabolic syndrome was 37·0 [%] . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 6 , 0 ###LEFT-WALL### 16 . 1 results 2 : 2 : 3 among 3 among 5 participants 4 the 5 participants 6 , 8 prevalence 6 , 13 was 7 the 8 prevalence 8 prevalence 9 of 8 prevalence 13 was 9 of 12 syndrome 10 the 12 syndrome 11 metabolic 12 syndrome 13 was 14 37·0 the mean 25 ohd level was 53·3 [nm] ; 47·8 [%] had 25 ohd levels below 50 nm . 0 ###LEFT-WALL### 5 level 0 ###LEFT-WALL### 6 was 0 ###LEFT-WALL### 9 ; 0 ###LEFT-WALL### 15 levels 0 ###LEFT-WALL### 19 . 1 the 5 level 2 mean 5 level 3 25 4 ohd 4 ohd 5 level 5 level 6 was 6 was 7 53·3 9 ; 10 47·8 9 ; 12 had 10 47·8 12 had 12 had 13 25 13 25 14 ohd 13 25 15 levels 14 ohd 15 levels 15 levels 16 below 16 below 18 nm 17 50 18 nm there was a significantly increased risk of the metabolic syndrome in the subjects with serum 25 ohd levels below 50 nm , compared with that of subjects with levels over 50 nm [[] odds ratio ( or [ )( 1·54 [;] 95 % confidence interval ( ci [ )(1·23 - 1·94 ] . 1 there 2 was 2 was 6 risk 2 was 11 in 2 was 14 with 3 a 6 risk 4 significantly 5 increased 5 increased 6 risk 6 risk 7 of 7 of 10 syndrome 8 the 10 syndrome 9 metabolic 10 syndrome 11 in 13 subjects 12 the 13 subjects 14 with 15 serum 15 serum 16 25 15 serum 17 ohd 15 serum 18 levels 17 ohd 18 levels 18 levels 19 below 18 levels 23 compared 18 levels 28 with 19 below 21 nm 20 50 21 nm 22 , 23 compared 23 compared 24 with 24 with 25 that 25 that 26 of 26 of 27 subjects 28 with 29 levels 28 with 30 over 30 over 35 ratio 31 50 32 nm 32 nm 34 odds 34 odds 35 ratio 35 ratio 45 interval 36 ( 45 interval 37 or 40 1·54 40 1·54 45 interval 42 95 45 interval 43 % 45 interval 44 confidence 45 interval 45 interval 51 1·94 45 interval 53 . 46 ( 51 1·94 47 ci 51 1·94 49 )(1·23 50 - 49 )(1·23 51 1·94 51 1·94 52 ] after adjustment for confounders , age , sex , season , years of education , alcohol use , total activity , smoking and pth , the or was 1·29 ( 95 % ci 1·00 - 1·68 ) . 0 ###LEFT-WALL### 23 and 0 ###LEFT-WALL### 29 1·29 0 ###LEFT-WALL### 38 . 1 after 2 adjustment 1 after 23 and 2 adjustment 3 for 3 for 4 confounders 4 confounders 6 age 5 , 6 age 6 age 7 , 8 sex 9 , 9 , 10 season 9 , 11 , 11 , 12 years 11 , 15 , 12 years 13 of 13 of 14 education 15 , 17 use 15 , 18 , 16 alcohol 17 use 18 , 20 activity 18 , 21 , 19 total 20 activity 21 , 22 smoking 21 , 23 and 23 and 24 pth 23 and 25 , 23 and 27 or 23 and 28 was 23 and 29 1·29 26 the 27 or 27 or 28 was 29 1·29 35 - 30 ( 35 - 31 95 32 % 32 % 34 1·00 33 ci 34 1·00 34 1·00 35 - 35 - 36 1·68 35 - 37 ) the association between vitamin d deficiency and the metabolic syndrome was mainly determined by the components low hdl and [(] high ) waist circumference . 0 ###LEFT-WALL### 2 association 0 ###LEFT-WALL### 11 was 0 ###LEFT-WALL### 25 . 1 the 2 association 2 association 3 between 2 association 11 was 3 between 7 and 4 vitamin 5 d 4 vitamin 6 deficiency 6 deficiency 7 and 7 and 10 syndrome 8 the 10 syndrome 9 metabolic 10 syndrome 11 was 12 mainly 11 was 13 determined 13 determined 14 by 14 by 19 and 15 the 18 hdl 16 components 18 hdl 17 low 18 hdl 18 hdl 19 and 19 and 24 circumference 21 high 22 ) 21 high 23 waist 23 waist 24 circumference conclusions : vitamin d deficiency is common in the older population in the netherlands , and subjects with serum 25 ohd below 50 nm have a higher risk of the metabolic syndrome . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 33 . 2 : 5 deficiency 2 : 6 is 2 : 16 and 3 vitamin 4 d 3 vitamin 5 deficiency 5 deficiency 6 is 6 is 7 common 7 common 8 in 7 common 12 in 8 in 11 population 9 the 11 population 10 older 11 population 12 in 14 netherlands 13 the 14 netherlands 15 , 16 and 16 and 17 subjects 16 and 25 have 17 subjects 18 with 17 subjects 25 have 18 with 21 ohd 19 serum 21 ohd 20 25 21 ohd 21 ohd 22 below 22 below 24 nm 23 50 24 nm 25 have 28 risk 26 a 28 risk 27 higher 28 risk 28 risk 29 of 29 of 32 syndrome 30 the 32 syndrome 31 metabolic 32 syndrome cancer in elderly patients is an increasingly common problem . 0 ###LEFT-WALL### 1 cancer 0 ###LEFT-WALL### 5 is 0 ###LEFT-WALL### 10 . 1 cancer 2 in 1 cancer 5 is 2 in 4 patients 3 elderly 4 patients 5 is 9 problem 6 an 9 problem 7 increasingly 8 common 8 common 9 problem older patients have more co - morbidity , therefore the toxic effects of chemotherapy treatment are less tolerable compared [to] younger patients . 0 ###LEFT-WALL### 2 patients 0 ###LEFT-WALL### 3 have 0 ###LEFT-WALL### 8 , 0 ###LEFT-WALL### 23 . 1 older 2 patients 2 patients 3 have 3 have 7 morbidity 4 more 5 co 5 co 6 - 5 co 7 morbidity 8 , 12 effects 8 , 16 are 9 therefore 12 effects 10 the 12 effects 11 toxic 12 effects 12 effects 13 of 12 effects 16 are 13 of 15 treatment 14 chemotherapy 15 treatment 16 are 22 patients 17 less 18 tolerable 18 tolerable 22 patients 19 compared 22 patients 21 younger 22 patients platinum - based compounds ( pbcs ) are commonly used cytotoxic agents in the treatment of several solid tumors ; however , their application is still limited in elderly patients , due to the risks in cardiovascular toxicity . 0 ###LEFT-WALL### 1 platinum 0 ###LEFT-WALL### 8 are 0 ###LEFT-WALL### 20 ; 0 ###LEFT-WALL### 39 . 1 platinum 4 compounds 1 platinum 8 are 2 - 4 compounds 3 based 4 compounds 4 compounds 6 pbcs 4 compounds 7 ) 5 ( 6 pbcs 6 pbcs 7 ) 8 are 9 commonly 8 are 12 agents 10 used 12 agents 11 cytotoxic 12 agents 12 agents 13 in 13 in 15 treatment 14 the 15 treatment 15 treatment 16 of 16 of 19 tumors 17 several 19 tumors 18 solid 19 tumors 20 ; 24 application 20 ; 27 limited 21 however 22 , 21 however 24 application 23 their 24 application 24 application 25 is 25 is 27 limited 26 still 27 limited 27 limited 28 in 27 limited 31 , 27 limited 32 due 28 in 30 patients 29 elderly 30 patients 32 due 33 to 32 due 36 in 33 to 35 risks 34 the 35 risks 36 in 38 toxicity 37 cardiovascular 38 toxicity the increased risk for myocardial ischemia , stroke , and vascular thrombosis linked with pbcs treatment is mainly due to reactive oxygen species ( ros ) production and the subsequent induction of oxidative stress and switch to a prothrombotic condition . 0 ###LEFT-WALL### 28 and 0 ###LEFT-WALL### 41 . 1 the 3 risk 2 increased 3 risk 3 risk 4 for 3 risk 7 , 4 for 6 ischemia 5 myocardial 6 ischemia 7 , 8 stroke 7 , 10 and 9 , 10 and 10 and 12 thrombosis 10 and 13 linked 10 and 28 and 11 vascular 12 thrombosis 13 linked 14 with 14 with 15 pbcs 14 with 27 production 15 pbcs 16 treatment 15 pbcs 17 is 15 pbcs 25 ros 16 treatment 17 is 17 is 18 mainly 17 is 20 to 19 due 20 to 20 to 23 species 21 reactive 22 oxygen 22 oxygen 23 species 24 ( 25 ros 25 ros 26 ) 28 and 31 induction 28 and 32 of 28 and 37 to 29 the 31 induction 30 subsequent 31 induction 32 of 35 and 33 oxidative 34 stress 34 stress 35 and 35 and 36 switch 37 to 40 condition 38 a 39 prothrombotic 38 a 40 condition 39 prothrombotic 40 condition recently , studies have shown a different genetic susceptibility in cardiovascular toxicity induced by therapy with pbcs . 0 ###LEFT-WALL### 3 studies 0 ###LEFT-WALL### 5 shown 0 ###LEFT-WALL### 18 . 1 recently 2 , 1 recently 3 studies 3 studies 4 have 4 have 5 shown 5 shown 9 susceptibility 5 shown 10 in 6 a 9 susceptibility 7 different 9 susceptibility 8 genetic 9 susceptibility 10 in 12 toxicity 11 cardiovascular 12 toxicity 12 toxicity 13 induced 13 induced 14 by 13 induced 16 with 14 by 15 therapy 16 with 17 pbcs antioxidants , such as vitamin e , selenium , lycopene , melatonin , and resveratrol , have been implicated in cancer treatment by their property to suppress the oxidant injury . 0 ###LEFT-WALL### 1 antioxidants 0 ###LEFT-WALL### 19 implicated 0 ###LEFT-WALL### 31 . 1 antioxidants 4 as 1 antioxidants 17 have 2 , 4 as 3 such 4 as 4 as 14 and 4 as 16 , 5 vitamin 6 e 5 vitamin 7 , 7 , 8 selenium 7 , 9 , 9 , 10 lycopene 9 , 11 , 11 , 12 melatonin 11 , 14 and 13 , 14 and 14 and 15 resveratrol 17 have 18 been 18 been 19 implicated 19 implicated 20 in 19 implicated 23 by 20 in 22 treatment 21 cancer 22 treatment 23 by 25 property 24 their 25 property 25 property 26 to 25 property 27 suppress 26 to 27 suppress 27 suppress 30 injury 28 the 30 injury 29 oxidant 30 injury resveratrol [,] especially [,] has been shown to increase the antineoplastic activity of cisplatin . 0 ###LEFT-WALL### 1 resveratrol 0 ###LEFT-WALL### 7 shown 0 ###LEFT-WALL### 15 . 1 resveratrol 5 has 3 especially 5 has 5 has 6 been 6 been 7 shown 7 shown 8 to 8 to 9 increase 9 increase 12 activity 10 the 12 activity 11 antineoplastic 12 activity 12 activity 13 of 13 of 14 cisplatin in addition , resveratrol 's ability to activate the sirtuin1 ( sirt1 ) pathway has been heavily implicated in the mechanisms controlling longevity and quality of life in the aged population . 0 ###LEFT-WALL### 6 ability 0 ###LEFT-WALL### 18 implicated 0 ###LEFT-WALL### 32 . 1 in 2 addition 1 in 3 , 1 in 6 ability 4 resveratrol 5 's 5 's 6 ability 6 ability 7 to 6 ability 8 activate 6 ability 15 has 7 to 8 activate 8 activate 14 pathway 9 the 14 pathway 10 sirtuin1 12 sirt1 10 sirtuin1 14 pathway 11 ( 12 sirt1 12 sirt1 13 ) 15 has 16 been 16 been 17 heavily 16 been 18 implicated 18 implicated 19 in 18 implicated 28 in 19 in 24 and 20 the 21 mechanisms 21 mechanisms 22 controlling 21 mechanisms 24 and 22 controlling 23 longevity 24 and 25 quality 24 and 26 of 26 of 27 life 28 in 31 population 29 the 31 population 30 aged 31 population this article reviews the current state of treatment with pbcs and their associated risk for cardiovascular disease . 0 ###LEFT-WALL### 2 article 0 ###LEFT-WALL### 3 reviews 0 ###LEFT-WALL### 18 . 1 this 2 article 2 article 3 reviews 3 reviews 6 state 3 reviews 9 with 4 the 6 state 5 current 6 state 6 state 7 of 7 of 8 treatment 9 with 11 and 10 pbcs 11 and 11 and 14 risk 11 and 15 for 12 their 14 risk 13 associated 14 risk 15 for 17 disease 16 cardiovascular 17 disease it discusses the most powerful antioxidant supplementation options as a possible strategy to reduce the cardiovascular toxicity effects of chemotherapy in the elderly . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 2 discusses 0 ###LEFT-WALL### 24 . 1 it 2 discusses 2 discusses 8 options 2 discusses 9 as 2 discusses 13 to 2 discusses 21 in 3 the 4 most 4 most 8 options 5 powerful 7 supplementation 6 antioxidant 7 supplementation 7 supplementation 8 options 9 as 12 strategy 10 a 12 strategy 11 possible 12 strategy 13 to 14 reduce 14 reduce 18 effects 15 the 18 effects 16 cardiovascular 17 toxicity 17 toxicity 18 effects 18 effects 19 of 19 of 20 chemotherapy 21 in 23 elderly 22 the 23 elderly background : although an influence of advancing age on lung cellularity in healthy subjects has already been described , induced sputum reference values for cell counts in older healthy adults are not available . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 23 values 2 : 31 are 2 : 34 . 3 although 5 influence 3 although 18 described 3 although 19 , 3 although 23 values 4 an 5 influence 5 influence 6 of 5 influence 9 on 5 influence 15 has 6 of 7 advancing 7 advancing 8 age 9 on 11 cellularity 10 lung 11 cellularity 11 cellularity 12 in 12 in 14 subjects 13 healthy 14 subjects 15 has 17 been 16 already 17 been 17 been 18 described 18 described 19 , 20 induced 23 values 21 sputum 22 reference 22 reference 23 values 23 values 24 for 23 values 27 in 23 values 31 are 24 for 26 counts 25 cell 26 counts 27 in 30 adults 28 older 30 adults 29 healthy 30 adults 31 are 32 not 31 are 33 available the aim of the present study was to evaluate the influence of age on the variation of sputum cell distribution in a considerable number of healthy subjects . 0 ###LEFT-WALL### 2 aim 0 ###LEFT-WALL### 28 . 1 the 2 aim 2 aim 3 of 2 aim 7 was 3 of 6 study 4 the 6 study 5 present 6 study 7 was 8 to 7 was 9 evaluate 8 to 9 evaluate 9 evaluate 11 influence 9 evaluate 14 on 9 evaluate 21 in 10 the 11 influence 11 influence 12 of 12 of 13 age 14 on 16 variation 15 the 16 variation 16 variation 17 of 17 of 20 distribution 18 sputum 19 cell 19 cell 20 distribution 21 in 27 subjects 22 a 24 number 23 considerable 24 number 24 number 25 of 24 number 27 subjects 25 of 27 subjects 26 healthy 27 subjects a total of 70 nonatopic , nonsmoker healthy subjects aged ≥50 years underwent sputum induction and blood cell count . 0 ###LEFT-WALL### 2 total 0 ###LEFT-WALL### 13 underwent 0 ###LEFT-WALL### 20 . 1 a 2 total 2 total 3 of 2 total 13 underwent 3 of 12 years 4 70 12 years 5 nonatopic 6 , 5 nonatopic 7 nonsmoker 7 nonsmoker 10 aged 8 healthy 9 subjects 9 subjects 10 aged 10 aged 12 years 11 ≥50 12 years 13 underwent 16 and 14 sputum 15 induction 15 induction 16 and 16 and 19 count 17 blood 19 count 18 cell 19 count sputum samples were processed and then were analyzed by optical microscopy . 0 ###LEFT-WALL### 2 samples 0 ###LEFT-WALL### 3 were 0 ###LEFT-WALL### 12 . 1 sputum 2 samples 2 samples 3 were 3 were 5 and 4 processed 5 and 5 and 7 were 5 and 9 by 6 then 7 were 7 were 8 analyzed 9 by 11 microscopy 10 optical 11 microscopy differential cell counts were reported as percentages and amount [of] [cells/mg] . 0 ###LEFT-WALL### 3 counts 0 ###LEFT-WALL### 5 reported 0 ###LEFT-WALL### 12 . 1 differential 2 cell 2 cell 3 counts 3 counts 4 were 4 were 5 reported 5 reported 6 as 6 as 8 and 7 percentages 8 and 8 and 9 amount results : sputum cell distribution of healthy subjects aged ≥50 years was mainly composed of neutrophils . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 5 distribution 2 : 15 of 2 : 17 . 3 sputum 5 distribution 4 cell 5 distribution 5 distribution 6 of 5 distribution 12 was 6 of 11 years 7 healthy 8 subjects 8 subjects 11 years 9 aged 10 ≥50 10 ≥50 11 years 12 was 15 of 13 mainly 15 of 14 composed 15 of 15 of 16 neutrophils both the percentage and the amount of sputum neutrophils correlated with the subjects ' age , r=0.5 , p=0.00001 and r=0.32 , p=0.007 , respectively . 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 26 . 1 both 4 and 2 the 3 percentage 3 percentage 4 and 4 and 6 amount 4 and 7 of 5 the 6 amount 7 of 9 neutrophils 8 sputum 9 neutrophils 9 neutrophils 10 correlated 10 correlated 11 with 10 correlated 25 respectively 11 with 20 and 12 the 13 subjects 13 subjects 14 ' 14 ' 15 age 15 age 16 , 16 , 19 p=0.00001 16 , 20 and 17 r=0.5 18 , 17 r=0.5 19 p=0.00001 20 and 21 r=0.32 20 and 23 p=0.007 22 , 23 p=0.007 23 p=0.007 24 , this correlation was more evident in women ( n=35 ) than in men ( n=35 ) . 0 ###LEFT-WALL### 2 correlation 0 ###LEFT-WALL### 3 was 0 ###LEFT-WALL### 17 . 1 this 2 correlation 2 correlation 3 was 3 was 5 evident 4 more 5 evident 5 evident 6 in 5 evident 11 than 6 in 7 women 7 women 9 n=35 8 ( 9 n=35 9 n=35 10 ) 11 than 12 in 12 in 13 men 13 men 15 n=35 14 ( 15 n=35 15 n=35 16 ) no correlation was found between blood neutrophils and age . 0 ###LEFT-WALL### 2 correlation 0 ###LEFT-WALL### 4 found 0 ###LEFT-WALL### 10 . 1 no 2 correlation 2 correlation 3 was 3 was 4 found 4 found 5 between 5 between 8 and 6 blood 7 neutrophils 7 neutrophils 8 and 8 and 9 age the increase in sputum neutrophils was not secondary to an increase in blood neutrophils . 0 ###LEFT-WALL### 2 increase 0 ###LEFT-WALL### 6 was 0 ###LEFT-WALL### 15 . 1 the 2 increase 2 increase 3 in 2 increase 6 was 3 in 5 neutrophils 4 sputum 5 neutrophils 6 was 7 not 6 was 8 secondary 7 not 8 secondary 8 secondary 9 to 8 secondary 12 in 9 to 11 increase 10 an 11 increase 12 in 14 neutrophils 13 blood 14 neutrophils conclusions : in the studied subjects , aging was associated , particularly in women , with an increase in sputum neutrophils not related to an increase of blood neutrophils . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 7 , 0 ###LEFT-WALL### 30 . 1 conclusions 2 : 2 : 3 in 3 in 6 subjects 4 the 6 subjects 5 studied 6 subjects 7 , 8 aging 7 , 10 associated 8 aging 9 was 9 was 10 associated 10 associated 13 in 10 associated 16 with 11 , 12 particularly 11 , 13 in 13 in 14 women 13 in 15 , 16 with 18 increase 16 with 22 not 16 with 24 to 17 an 18 increase 18 increase 19 in 19 in 21 neutrophils 20 sputum 21 neutrophils 22 not 23 related 24 to 26 increase 25 an 26 increase 26 increase 27 of 27 of 29 neutrophils 28 blood 29 neutrophils these results could be useful in clinical and experimental settings as reference values to compare with data from subjects aged over 50 years . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 4 be 0 ###LEFT-WALL### 24 . 1 these 2 results 2 results 3 could 3 could 4 be 4 be 5 useful 5 useful 6 in 5 useful 11 as 5 useful 14 to 5 useful 15 compare 6 in 10 settings 7 clinical 8 and 8 and 9 experimental 8 and 10 settings 11 as 13 values 12 reference 13 values 14 to 15 compare 15 compare 16 with 16 with 17 data 17 data 18 from 17 data 20 aged 18 from 19 subjects 20 aged 21 over 21 over 23 years 22 50 23 years these data showed that sputum neutrophila can be dissociated from airway symptoms and could create a favorable background for the development of age - related lung diseases . 0 ###LEFT-WALL### 2 data 0 ###LEFT-WALL### 3 showed 0 ###LEFT-WALL### 25 related 0 ###LEFT-WALL### 28 . 1 these 2 data 2 data 3 showed 3 showed 4 that 4 that 6 neutrophila 4 that 13 and 5 sputum 6 neutrophila 6 neutrophila 7 can 7 can 13 and 8 be 9 dissociated 8 be 13 and 9 dissociated 10 from 10 from 12 symptoms 11 airway 12 symptoms 13 and 14 could 13 and 19 for 14 could 15 create 15 create 18 background 16 a 17 favorable 16 a 18 background 17 favorable 18 background 19 for 21 development 20 the 21 development 21 development 22 of 22 of 23 age 24 - 25 related 25 related 27 diseases 26 lung 27 diseases abstract improved growth characteristics of the aging bone marrow cells subsequent to neuropeptide y ( npy [ neuropeptide] y y5 [receptor] ( npy y5r ) ligand - receptor interaction . 0 ###LEFT-WALL### 4 characteristics 0 ###LEFT-WALL### 25 ) 0 ###LEFT-WALL### 26 ligand 1 abstract 4 characteristics 2 improved 3 growth 3 growth 4 characteristics 4 characteristics 5 of 4 characteristics 11 subsequent 4 characteristics 25 ) 5 of 10 cells 6 the 10 cells 7 aging 8 bone 8 bone 10 cells 9 marrow 10 cells 11 subsequent 12 to 12 to 13 neuropeptide 13 neuropeptide 14 y 13 neuropeptide 23 npy 15 ( 23 npy 16 npy 18 neuropeptide] 18 neuropeptide] 19 y 19 y 22 ( 21 [receptor] 22 ( 22 ( 23 npy 23 npy 24 y5r 26 ligand 28 receptor 26 ligand 29 interaction 27 - 28 receptor bone marrow cells were isolated from neonatal ( 2 - 3 weeks ) , young ( 8 - 12 weeks ) , and old ( 24 - 28 months [ )(rats on the basis of their preferential adherence to plastic surface . 0 ###LEFT-WALL### 1 bone 1 bone 2 marrow 1 bone 23 and 1 bone 27 - 2 marrow 3 cells 2 marrow 6 from 3 cells 4 were 4 were 5 isolated 5 isolated 6 from 7 neonatal 10 - 7 neonatal 14 , 8 ( 10 - 9 2 10 - 10 - 12 weeks 10 - 13 ) 11 3 12 weeks 14 , 15 young 14 , 23 and 15 young 18 - 16 ( 18 - 17 8 18 - 18 - 20 weeks 18 - 21 ) 19 12 20 weeks 22 , 23 and 23 and 24 old 25 ( 27 - 26 24 27 - 27 - 29 months 27 - 42 . 28 28 29 months 29 months 31 )(rats 29 months 41 surface 31 )(rats 32 on 31 )(rats 35 of 31 )(rats 39 to 31 )(rats 41 surface 32 on 34 basis 33 the 34 basis 35 of 38 adherence 36 their 38 adherence 37 preferential 38 adherence 39 to 40 plastic after culturing the cells at initial seeding density of 1×10 ( 4 ) cells/cm ( 2 ) , we found that the proliferation potential of bone marrow cells declined with age . 0 ###LEFT-WALL### 19 we 0 ###LEFT-WALL### 20 found 0 ###LEFT-WALL### 32 . 1 after 2 culturing 1 after 18 , 1 after 19 we 2 culturing 4 cells 2 culturing 5 at 3 the 4 cells 5 at 8 density 6 initial 8 density 7 seeding 8 density 8 density 9 of 8 density 16 2 9 of 14 cells/cm 10 1×10 12 4 10 1×10 14 cells/cm 11 ( 12 4 12 4 13 ) 15 ( 16 2 16 2 17 ) 19 we 20 found 20 found 21 that 21 that 24 potential 21 that 29 declined 22 the 24 potential 23 proliferation 24 potential 24 potential 25 of 24 potential 29 declined 25 of 28 cells 26 bone 28 cells 27 marrow 28 cells 29 declined 30 with 30 with 31 age real - time polymerase chain reaction ( pcr ) and western blotting showed that bone marrow cells in different age groups constitutively expressed npy and npy receptor [subtypes] ( y1r , y2r , and y5r ) . 0 ###LEFT-WALL### 3 time 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 37 . 1 real 2 - 1 real 3 time 3 time 6 reaction 4 polymerase 6 reaction 5 chain 6 reaction 6 reaction 8 pcr 7 ( 8 pcr 8 pcr 9 ) 10 and 12 blotting 10 and 13 showed 11 western 12 blotting 12 blotting 13 showed 13 showed 14 that 14 that 17 cells 14 that 23 expressed 15 bone 17 cells 16 marrow 17 cells 17 cells 18 in 17 cells 23 expressed 18 in 21 groups 19 different 21 groups 20 age 21 groups 22 constitutively 23 expressed 23 expressed 25 and 24 npy 25 and 25 and 27 receptor 25 and 30 y1r 26 npy 27 receptor 29 ( 30 y1r 30 y1r 34 and 30 y1r 36 ) 31 , 34 and 32 y2r 34 and 33 , 34 and 34 and 35 y5r 34 and 36 ) however , npy and y5r expression increased by more than 130 - fold and decreased by 28 - fold , respectively , in old bone marrow cells as compared to young bone marrow cells . 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 7 increased 0 ###LEFT-WALL### 12 - 0 ###LEFT-WALL### 35 . 1 however 2 , 1 however 4 and 3 npy 4 and 4 and 6 expression 4 and 7 increased 5 y5r 6 expression 7 increased 8 by 8 by 11 130 9 more 10 than 10 than 11 130 12 - 14 and 12 - 18 - 12 - 29 compared 13 fold 14 and 14 and 15 decreased 15 decreased 16 by 16 by 17 28 18 - 19 fold 19 fold 21 respectively 19 fold 23 in 19 fold 28 as 20 , 21 respectively 21 respectively 22 , 23 in 27 cells 24 old 25 bone 25 bone 27 cells 26 marrow 27 cells 28 as 29 compared 29 compared 30 to 30 to 34 cells 31 young 34 cells 32 bone 34 cells 33 marrow 34 cells npy ( 10 nm ) stimulated the proliferation of all bone marrow cells age groups , and their proliferation was blocked by y5r [antagonist] . 0 ###LEFT-WALL### 1 npy 0 ###LEFT-WALL### 6 stimulated 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 25 . 1 npy 4 nm 1 npy 6 stimulated 2 ( 4 nm 3 10 4 nm 4 nm 5 ) 6 stimulated 8 proliferation 7 the 8 proliferation 8 proliferation 9 of 9 of 13 cells 10 all 13 cells 11 bone 13 cells 12 marrow 13 cells 13 cells 14 age 13 cells 15 groups 14 age 15 groups 16 , 17 and 17 and 19 proliferation 17 and 21 blocked 18 their 19 proliferation 19 proliferation 20 was 20 was 21 blocked 21 blocked 22 by 22 by 23 y5r however , the pro [-] proliferative effect of npy on old bone marrow cells was weaker than other cell groups due to lower y5r expression . 0 ###LEFT-WALL### 7 effect 0 ###LEFT-WALL### 23 lower 0 ###LEFT-WALL### 26 . 1 however 2 , 1 however 7 effect 3 the 7 effect 4 pro 7 effect 6 proliferative 7 effect 7 effect 8 of 7 effect 15 was 8 of 9 npy 9 npy 10 on 10 on 14 cells 11 old 12 bone 12 bone 14 cells 13 marrow 14 cells 15 was 16 weaker 16 weaker 17 than 17 than 20 groups 18 other 20 groups 19 cell 20 groups 20 groups 21 due 21 due 22 to 22 to 23 lower 23 lower 25 expression 24 y5r 25 expression y5r gene transfection of old bone marrow cells with subsequent npy ( 3 - 36 ) ( 10 nm ) treatment significantly increased proliferation [of] old bone marrow cells ( >56 [%] ) as compared to green fluorescence protein - transfected control old bone marrow cells . 0 ###LEFT-WALL### 3 transfection 0 ###LEFT-WALL### 35 compared 1 y5r 2 gene 2 gene 3 transfection 3 transfection 4 of 3 transfection 23 increased 4 of 8 cells 5 old 6 bone 6 bone 8 cells 7 marrow 8 cells 8 cells 9 with 9 with 21 treatment 10 subsequent 21 treatment 11 npy 14 - 11 npy 19 nm 11 npy 21 treatment 12 ( 14 - 13 3 14 - 14 - 15 36 14 - 16 ) 17 ( 19 nm 18 10 19 nm 19 nm 20 ) 22 significantly 23 increased 23 increased 29 cells 23 increased 34 as 24 proliferation 27 bone 26 old 27 bone 27 bone 29 cells 28 marrow 29 cells 29 cells 31 >56 30 ( 31 >56 31 >56 33 ) 34 as 35 compared 35 compared 36 to 36 to 37 green 37 green 39 protein 38 fluorescence 39 protein 39 protein 46 cells 40 - 46 cells 41 transfected 42 control 42 control 44 bone 43 old 44 bone 44 bone 45 marrow 45 marrow 46 cells 46 cells 47 . stimulation of old bone marrow cells by npy treatment rejuvenated the growth characteristics of aging bone marrow cells as a result of y5r overexpression . 0 ###LEFT-WALL### 1 stimulation 0 ###LEFT-WALL### 10 rejuvenated 0 ###LEFT-WALL### 25 . 1 stimulation 2 of 1 stimulation 10 rejuvenated 2 of 6 cells 3 old 4 bone 4 bone 6 cells 5 marrow 6 cells 6 cells 7 by 7 by 9 treatment 8 npy 9 treatment 10 rejuvenated 13 characteristics 11 the 13 characteristics 12 growth 13 characteristics 13 characteristics 14 of 14 of 15 aging 15 aging 18 cells 15 aging 19 as 16 bone 18 cells 17 marrow 18 cells 19 as 21 result 20 a 21 result 21 result 22 of 22 of 24 overexpression 23 y5r 24 overexpression none none none this study prospectively examined all initial emergency and short - term detention orders of older adults under the mental health ( care and treatment ) ( scotland ) act 2003 in a scottish health region in 2008 to determine differences in characteristics and outcomes by patients ' age , gender and those detained by consultant compared [with] [non] - consultant clinicians . 0 ###LEFT-WALL### 1 none 0 ###LEFT-WALL### 9 initial 1 none 5 study 1 none 7 examined 1 none 9 initial 2 none 3 none 3 none 5 study 4 this 5 study 5 study 7 examined 6 prospectively 7 examined 8 all 9 initial 9 initial 16 orders 9 initial 20 under 10 emergency 11 and 11 and 14 term 11 and 16 orders 12 short 13 - 12 short 14 term 15 detention 16 orders 16 orders 17 of 17 of 19 adults 18 older 19 adults 20 under 32 act 21 the 32 act 22 mental 23 health 23 health 26 and 23 health 32 act 24 ( 26 and 25 care 26 and 26 and 27 treatment 26 and 28 ) 26 and 30 scotland 26 and 31 ) 29 ( 30 scotland 30 scotland 31 ) 32 act 33 2003 32 act 34 in 32 act 39 in 32 act 41 to 32 act 42 determine 34 in 38 region 35 a 38 region 36 scottish 38 region 37 health 38 region 39 in 40 2008 41 to 42 determine 42 determine 43 differences 42 determine 48 by 43 differences 44 in 44 in 46 and 45 characteristics 46 and 46 and 47 outcomes 48 by 54 and 49 patients 50 ' 50 ' 51 age 51 age 52 , 52 , 53 gender 52 , 54 and 54 and 55 those 54 and 65 . 55 those 56 detained 56 detained 57 by 57 by 58 consultant 58 consultant 59 compared 58 consultant 64 clinicians 62 - 64 clinicians 63 consultant 64 clinicians 64 clinicians 65 . detention order papers were scrutinized , the detaining practitioners were interviewed and case records were examined . 0 ###LEFT-WALL### 3 papers 0 ###LEFT-WALL### 5 scrutinized 0 ###LEFT-WALL### 6 , 0 ###LEFT-WALL### 17 . 1 detention 3 papers 2 order 3 papers 3 papers 4 were 4 were 5 scrutinized 6 , 9 practitioners 6 , 11 interviewed 6 , 12 and 7 the 9 practitioners 8 detaining 9 practitioners 9 practitioners 10 were 10 were 11 interviewed 12 and 14 records 12 and 16 examined 13 case 14 records 14 records 15 were 15 were 16 examined appropriate statistical analyses were performed . 0 ###LEFT-WALL### 3 analyses 0 ###LEFT-WALL### 5 performed 0 ###LEFT-WALL### 6 . 1 appropriate 3 analyses 2 statistical 3 analyses 3 analyses 4 were 4 were 5 performed for the 87 detentions , subjects were caucasian [,] [male] ( 54 % ) and 45 % were aged 80 years or older . 0 ###LEFT-WALL### 6 subjects 0 ###LEFT-WALL### 7 were 0 ###LEFT-WALL### 15 and 0 ###LEFT-WALL### 24 . 1 for 4 detentions 1 for 5 , 1 for 6 subjects 2 the 3 87 3 87 4 detentions 6 subjects 7 were 7 were 8 caucasian 8 caucasian 13 % 11 ( 13 % 12 54 13 % 13 % 14 ) 15 and 17 % 15 and 19 aged 16 45 17 % 17 % 18 were 18 were 19 aged 19 aged 22 or 20 80 21 years 21 years 22 or 22 or 23 older ninety - four percent of detentions occurred on a weekday , during working hours ( 87 % ) , in hospital [(] [67] % ) with consultants initiating 74 % of orders . 0 ###LEFT-WALL### 4 percent 0 ###LEFT-WALL### 7 occurred 0 ###LEFT-WALL### 33 . 1 ninety 2 - 2 - 3 four 2 - 4 percent 4 percent 5 of 4 percent 7 occurred 5 of 6 detentions 7 occurred 8 on 7 occurred 20 in 7 occurred 26 with 8 on 10 weekday 9 a 10 weekday 10 weekday 12 during 11 , 12 during 12 during 14 hours 12 during 19 , 13 working 14 hours 14 hours 17 % 15 ( 17 % 16 87 17 % 17 % 18 ) 19 , 20 in 20 in 24 % 20 in 25 ) 21 hospital 24 % 26 with 27 consultants 27 consultants 28 initiating 28 initiating 30 % 29 74 30 % 30 % 31 of 31 of 32 orders detention rates ranged from 66 to 171 per 100,000 [over] - 65 s . 0 ###LEFT-WALL### 2 rates 0 ###LEFT-WALL### 3 ranged 0 ###LEFT-WALL### 14 . 1 detention 2 rates 2 rates 3 ranged 3 ranged 4 from 4 from 6 to 5 66 6 to 6 to 7 171 6 to 8 per 8 per 13 s 9 100,000 11 - 11 - 12 65 11 - 13 s seventy - five percent of patients had an organic disorder , 46 % exhibiting psychotic symptoms . 0 ###LEFT-WALL### 4 percent 0 ###LEFT-WALL### 7 had 1 seventy 2 - 2 - 3 five 2 - 4 percent 4 percent 5 of 4 percent 7 had 5 of 6 patients 7 had 10 disorder 8 an 9 organic 8 an 10 disorder 9 organic 10 disorder 10 disorder 13 % 11 , 13 % 12 46 13 % 13 % 14 exhibiting 13 % 17 . 14 exhibiting 16 symptoms 15 psychotic 16 symptoms the older group had higher rates of confusion , organic diagnoses , but lower levels of previous psychiatric admissions . 0 ###LEFT-WALL### 3 group 0 ###LEFT-WALL### 4 had 0 ###LEFT-WALL### 20 . 1 the 3 group 2 older 3 group 3 group 4 had 4 had 6 rates 5 higher 6 rates 6 rates 7 of 7 of 15 levels 8 confusion 9 , 9 , 11 diagnoses 9 , 13 but 10 organic 11 diagnoses 12 , 13 but 13 but 14 lower 13 but 15 levels 15 levels 16 of 16 of 19 admissions 17 previous 19 admissions 18 psychiatric 19 admissions consultants were more likely to detain patients with a wider variety of disorders , with more admissions [to] and detentions in psychiatric hospital care . 0 ###LEFT-WALL### 1 consultants 0 ###LEFT-WALL### 2 were 1 consultants 2 were 2 were 4 likely 3 more 4 likely 4 likely 5 to 4 likely 6 detain 5 to 6 detain 6 detain 7 patients 6 detain 8 with 8 with 11 variety 9 a 11 variety 10 wider 11 variety 11 variety 12 of 11 variety 15 with 12 of 13 disorders 14 , 15 with 15 with 19 and 15 with 25 . 16 more 17 admissions 17 admissions 19 and 19 and 20 detentions 19 and 21 in 21 in 24 care 22 psychiatric 23 hospital 23 hospital 24 care final detention outcomes were significantly different between the consultant and [non] [-] consultant groups . 0 ###LEFT-WALL### 3 outcomes 0 ###LEFT-WALL### 4 were 0 ###LEFT-WALL### 15 . 1 final 2 detention 2 detention 3 outcomes 3 outcomes 4 were 4 were 6 different 5 significantly 6 different 6 different 7 between 7 between 10 and 8 the 9 consultant 9 consultant 10 and 10 and 14 groups 13 consultant 14 groups the results indicated few differences between the genders , but differences were more significant between the age cohorts and were further influenced by the grade of the detaining clinician . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 indicated 0 ###LEFT-WALL### 10 but 0 ###LEFT-WALL### 30 . 1 the 2 results 2 results 3 indicated 3 indicated 5 differences 3 indicated 6 between 4 few 5 differences 6 between 8 genders 7 the 8 genders 9 , 10 but 10 but 11 differences 10 but 19 and 11 differences 19 and 12 were 14 significant 12 were 19 and 13 more 14 significant 14 significant 15 between 15 between 18 cohorts 16 the 18 cohorts 17 age 18 cohorts 19 and 20 were 19 and 29 clinician 20 were 22 influenced 21 further 22 influenced 22 influenced 23 by 23 by 25 grade 24 the 25 grade 25 grade 26 of 26 of 28 detaining 27 the 28 detaining further research is required to examine the influence [that] community mental health teams , advance statements and the use [of] guardianship and incapacity legislation have on the increasing rates of mental health detentions in the aging population . 0 ###LEFT-WALL### 2 research 0 ###LEFT-WALL### 4 required 0 ###LEFT-WALL### 38 . 1 further 2 research 2 research 3 is 3 is 4 required 4 required 5 to 4 required 26 on 5 to 6 examine 6 examine 10 community 7 the 10 community 8 influence 10 community 10 community 13 teams 10 community 25 have 11 mental 12 health 12 health 13 teams 13 teams 25 have 14 , 15 advance 15 advance 22 and 15 advance 25 have 16 statements 17 and 17 and 21 guardianship 17 and 22 and 18 the 21 guardianship 19 use 21 guardianship 22 and 24 legislation 23 incapacity 24 legislation 26 on 29 rates 27 the 29 rates 28 increasing 29 rates 29 rates 30 of 29 rates 34 in 30 of 33 detentions 31 mental 32 health 32 health 33 detentions 34 in 37 population 35 the 37 population 36 aging 37 population recently , the number of elderly patients with dementia has been increasing in japan because of both the extension of average life expectancy and a considerable rise in the incidence of dementia with age . 0 ###LEFT-WALL### 4 number 0 ###LEFT-WALL### 11 been 0 ###LEFT-WALL### 35 . 1 recently 2 , 1 recently 4 number 3 the 4 number 4 number 5 of 4 number 10 has 5 of 7 patients 6 elderly 7 patients 7 patients 8 with 8 with 9 dementia 10 has 11 been 11 been 12 increasing 12 increasing 13 in 12 increasing 16 of 12 increasing 28 in 12 increasing 33 with 13 in 14 japan 15 because 16 of 16 of 24 and 17 both 24 and 18 the 19 extension 19 extension 20 of 19 extension 24 and 20 of 23 expectancy 21 average 22 life 22 life 23 expectancy 24 and 27 rise 25 a 26 considerable 25 a 27 rise 26 considerable 27 rise 28 in 30 incidence 29 the 30 incidence 30 incidence 31 of 31 of 32 dementia 33 with 34 age for these reasons , dementia in japan has become common , and more than half of all cases are alzheimer disease . 0 ###LEFT-WALL### 5 dementia 0 ###LEFT-WALL### 9 become 0 ###LEFT-WALL### 22 . 1 for 3 reasons 1 for 4 , 1 for 5 dementia 2 these 3 reasons 5 dementia 6 in 5 dementia 8 has 6 in 7 japan 8 has 9 become 9 become 12 and 9 become 14 than 9 become 21 disease 10 common 12 and 11 , 12 and 12 and 13 more 14 than 15 half 14 than 19 are 15 half 16 of 15 half 19 are 16 of 18 cases 17 all 18 cases 19 are 20 alzheimer furthermore , several studies have suggested that a high intake of vegetables and fish , an active daily life , and lifelong education might positively influence cognitive function as neuroprotective factors . 0 ###LEFT-WALL### 4 studies 0 ###LEFT-WALL### 6 suggested 0 ###LEFT-WALL### 32 . 1 furthermore 2 , 1 furthermore 4 studies 3 several 4 studies 4 studies 5 have 5 have 6 suggested 6 suggested 7 that 7 that 21 and 7 that 26 influence 8 a 10 intake 9 high 10 intake 10 intake 11 of 10 intake 21 and 11 of 13 and 12 vegetables 13 and 13 and 14 fish 13 and 15 , 13 and 19 life 15 , 19 life 16 an 17 active 16 an 19 life 17 active 19 life 18 daily 19 life 19 life 20 , 20 , 21 and 21 and 23 education 21 and 24 might 22 lifelong 23 education 24 might 26 influence 25 positively 26 influence 26 influence 31 factors 27 cognitive 28 function 28 function 31 factors 29 as 30 neuroprotective 30 neuroprotective 31 factors therefore , we should try to prevent dementia based on the clinical and hygienic management of the lifestyles and lifestyle - related diseases , even in the youth . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 5 try 0 ###LEFT-WALL### 29 . 1 therefore 2 , 1 therefore 3 we 3 we 4 should 4 should 5 try 5 try 6 to 5 try 7 prevent 6 to 7 prevent 7 prevent 8 dementia 7 prevent 10 on 7 prevent 25 even 8 dementia 9 based 10 on 15 management 11 the 15 management 12 clinical 13 and 13 and 14 hygienic 13 and 15 management 15 management 16 of 16 of 19 and 17 the 18 lifestyles 18 lifestyles 19 and 19 and 20 lifestyle 19 and 23 diseases 21 - 23 diseases 22 related 23 diseases 23 diseases 24 , 25 even 26 in 26 in 28 youth 27 the 28 youth [none] alzheimer 's disease is a 100 [-] year [-] old concept . 0 ###LEFT-WALL### 4 disease 0 ###LEFT-WALL### 5 is 0 ###LEFT-WALL### 13 . 2 alzheimer 3 's 3 's 4 disease 4 disease 5 is 5 is 12 concept 6 a 12 concept 7 100 9 year 9 year 12 concept 11 old 12 concept as a diagnostic label , it has evolved over the 20th and 21st centuries from a rare diagnosis in younger patients to a worldwide epidemic common in the elderly , said to affect over 35 million people worldwide . 0 ###LEFT-WALL### 6 it 0 ###LEFT-WALL### 33 affect 0 ###LEFT-WALL### 39 . 1 as 4 label 1 as 5 , 1 as 6 it 2 a 3 diagnostic 2 a 4 label 3 diagnostic 4 label 6 it 30 , 7 has 8 evolved 7 has 30 , 8 evolved 9 over 8 evolved 19 in 8 evolved 22 to 9 over 14 centuries 10 the 11 20th 11 20th 12 and 12 and 13 21st 12 and 14 centuries 14 centuries 15 from 15 from 18 diagnosis 16 a 17 rare 16 a 18 diagnosis 17 rare 18 diagnosis 19 in 21 patients 20 younger 21 patients 22 to 25 epidemic 23 a 24 worldwide 23 a 25 epidemic 24 worldwide 25 epidemic 25 epidemic 26 common 26 common 27 in 27 in 29 elderly 28 the 29 elderly 30 , 31 said 30 , 32 to 32 to 33 affect 33 affect 37 people 33 affect 38 worldwide 34 over 36 million 35 35 36 million 36 million 37 people in this opinion piece , we use a constructivist approach to review the early history of the terms " alzheimer 's disease " and related concepts such as dementia , as well as the more recent nosological changes that have occurred in the four major editions of the diagnostic and statistical manual since 1952 . 0 ###LEFT-WALL### 6 we 0 ###LEFT-WALL### 24 and 1 in 4 piece 1 in 5 , 1 in 6 we 2 this 4 piece 3 opinion 4 piece 6 we 7 use 7 use 10 approach 7 use 11 to 8 a 10 approach 9 constructivist 10 approach 11 to 24 and 12 review 15 history 12 review 24 and 13 the 15 history 14 early 15 history 15 history 16 of 16 of 22 disease 17 the 18 terms 18 terms 19 " 18 terms 20 alzheimer 20 alzheimer 21 's 21 's 22 disease 22 disease 23 " 24 and 25 related 24 and 26 concepts 26 concepts 28 as 27 such 28 as 28 as 29 dementia 29 dementia 33 as 30 , 33 as 31 as 32 well 32 well 33 as 33 as 38 changes 33 as 55 . 34 the 38 changes 35 more 36 recent 36 recent 38 changes 37 nosological 38 changes 38 changes 39 that 38 changes 40 have 39 that 40 have 40 have 41 occurred 41 occurred 42 in 42 in 46 editions 43 the 46 editions 44 four 46 editions 45 major 46 editions 46 editions 47 of 46 editions 53 since 47 of 52 manual 48 the 52 manual 49 diagnostic 50 and 50 and 51 statistical 51 statistical 52 manual 53 since 54 1952 a critical engagement of the history of alzheimer 's disease and dementia , specifically the evolution of those concepts in the dsm over the past 100 years , raises a number of questions about how those labels and emergent diagnoses , such as neurocognitive disorders and mild cognitive impairment , might continue to evolve in the dsm - v , due for release [in] 2013 . 0 ###LEFT-WALL### 3 engagement 0 ###LEFT-WALL### 9 's 0 ###LEFT-WALL### 11 and 1 a 3 engagement 2 critical 3 engagement 3 engagement 4 of 3 engagement 9 's 4 of 6 history 5 the 6 history 6 history 7 of 7 of 8 alzheimer 9 's 10 disease 11 and 12 dementia 11 and 29 raises 12 dementia 16 evolution 12 dementia 29 raises 13 , 14 specifically 13 , 16 evolution 15 the 16 evolution 16 evolution 17 of 16 evolution 28 , 17 of 19 concepts 18 those 19 concepts 19 concepts 20 in 20 in 22 dsm 21 the 22 dsm 22 dsm 23 over 23 over 27 years 24 the 27 years 25 past 27 years 26 100 27 years 29 raises 33 questions 29 raises 53 to 29 raises 55 in 30 a 31 number 31 number 32 of 31 number 33 questions 32 of 33 questions 33 questions 34 about 34 about 35 how 35 how 38 and 35 how 52 continue 36 those 37 labels 37 labels 38 and 38 and 40 diagnoses 38 and 41 , 38 and 43 as 38 and 51 might 39 emergent 40 diagnoses 42 such 43 as 43 as 46 and 44 neurocognitive 45 disorders 45 disorders 46 and 46 and 49 impairment 46 and 50 , 47 mild 48 cognitive 48 cognitive 49 impairment 51 might 52 continue 53 to 54 evolve 55 in 57 dsm 56 the 57 dsm 57 dsm 59 v 57 dsm 61 due 58 - 59 v 59 v 60 , 60 , 61 due 61 due 62 for 61 due 66 . 62 for 63 release 63 release 65 2013 in alzheimer 's disease ( ad ) , lipid alterations are present early during disease progression . 0 ###LEFT-WALL### 10 alterations 0 ###LEFT-WALL### 11 are 0 ###LEFT-WALL### 17 . 1 in 4 disease 1 in 8 , 1 in 10 alterations 2 alzheimer 3 's 3 's 4 disease 4 disease 6 ad 5 ( 6 ad 6 ad 7 ) 9 lipid 10 alterations 10 alterations 11 are 11 are 12 present 12 present 13 early 12 present 14 during 14 during 16 progression 15 disease 16 progression as some of these alterations point towards a peroxisomal dysfunction , we investigated peroxisomes in human postmortem brains obtained from the cohort - based , longitudinal vienna - transdanube aging ( vita ) study . 0 ###LEFT-WALL### 12 we 0 ###LEFT-WALL### 13 investigated 0 ###LEFT-WALL### 25 , 0 ###LEFT-WALL### 35 . 1 as 5 alterations 1 as 6 point 1 as 11 , 1 as 12 we 2 some 3 of 2 some 5 alterations 3 of 5 alterations 4 these 5 alterations 5 alterations 6 point 6 point 7 towards 7 towards 10 dysfunction 8 a 9 peroxisomal 8 a 10 dysfunction 9 peroxisomal 10 dysfunction 12 we 13 investigated 13 investigated 14 peroxisomes 13 investigated 20 from 13 investigated 24 based 14 peroxisomes 15 in 15 in 18 brains 16 human 18 brains 17 postmortem 18 brains 18 brains 19 obtained 20 from 22 cohort 21 the 22 cohort 23 - 24 based 24 based 25 , 25 , 27 vienna 25 , 28 - 26 longitudinal 27 vienna 28 - 34 study 29 transdanube 30 aging 30 aging 32 vita 31 ( 32 vita 32 vita 33 ) 32 vita 34 study based on the neuropathological braak staging for ad on one hemisphere , the patients were grouped into three cohorts of increasing severity ( stages i - ii , iii - iv , and v - vi , respectively ) . 0 ###LEFT-WALL### 14 patients 0 ###LEFT-WALL### 16 grouped 0 ###LEFT-WALL### 40 . 1 based 2 on 1 based 9 on 1 based 12 , 1 based 14 patients 2 on 6 staging 3 the 6 staging 4 neuropathological 6 staging 5 braak 6 staging 6 staging 7 for 7 for 8 ad 9 on 11 hemisphere 10 one 11 hemisphere 13 the 14 patients 14 patients 15 were 15 were 16 grouped 16 grouped 17 into 16 grouped 38 respectively 17 into 19 cohorts 18 three 19 cohorts 19 cohorts 20 of 19 cohorts 24 stages 20 of 21 increasing 21 increasing 22 severity 23 ( 24 stages 24 stages 25 i 24 stages 27 ii 24 stages 29 iii 24 stages 36 vi 24 stages 37 , 26 - 27 ii 27 ii 28 , 28 , 29 iii 29 iii 33 and 29 iii 35 - 30 - 33 and 31 iv 33 and 32 , 33 and 33 and 34 v 33 and 35 - 35 - 36 vi 36 vi 37 , 37 , 38 respectively 38 respectively 39 ) lipid analyses of cortical regions from the other hemisphere revealed accumulation of c22:0 and very long - chain fatty acids ( vlcfa , c24:0 and c26:0 ) , all substrates for peroxisomal β - oxidation , in cases with stages v - [vi] pathology compared with those modestly affected ( stages i - ii ) . 0 ###LEFT-WALL### 1 lipid 0 ###LEFT-WALL### 2 analyses 1 lipid 2 analyses 2 analyses 30 substrates 2 analyses 45 compared 3 of 14 and 3 of 30 substrates 4 cortical 5 regions 5 regions 6 from 5 regions 14 and 6 from 11 accumulation 7 the 8 other 8 other 11 accumulation 9 hemisphere 11 accumulation 10 revealed 11 accumulation 11 accumulation 12 of 12 of 13 c22:0 14 and 20 acids 14 and 25 and 15 very 16 long 16 long 17 - 16 long 18 chain 18 chain 20 acids 19 fatty 20 acids 21 ( 25 and 22 vlcfa 23 , 23 , 24 c24:0 23 , 25 and 25 and 26 c26:0 25 and 27 ) 25 and 28 , 29 all 30 substrates 30 substrates 31 for 30 substrates 45 compared 31 for 44 pathology 32 peroxisomal 44 pathology 33 β 35 oxidation 33 β 42 - 33 β 44 pathology 34 - 35 oxidation 35 oxidation 37 in 35 oxidation 42 - 36 , 37 in 37 in 38 cases 37 in 42 - 38 cases 39 with 39 with 40 stages 40 stages 41 v 45 compared 46 with 46 with 47 those 47 those 49 affected 47 those 51 stages 48 modestly 49 affected 50 ( 51 stages 51 stages 52 i 51 stages 54 ii 51 stages 56 . 53 - 54 ii 54 ii 55 ) conversely , the level of plasmalogens , which need intact peroxisomes for their biosynthesis , was decreased in severely affected tissues , in agreement with a peroxisomal dysfunction . 0 ###LEFT-WALL### 4 level 0 ###LEFT-WALL### 17 decreased 1 conversely 2 , 1 conversely 4 level 3 the 4 level 4 level 5 of 4 level 16 was 5 of 6 plasmalogens 6 plasmalogens 8 which 7 , 8 which 8 which 9 need 8 which 15 , 9 need 11 peroxisomes 10 intact 11 peroxisomes 11 peroxisomes 12 for 12 for 14 biosynthesis 13 their 14 biosynthesis 16 was 17 decreased 17 decreased 18 in 18 in 21 tissues 19 severely 20 affected 20 affected 21 tissues 21 tissues 23 in 22 , 23 in 23 in 24 agreement 23 in 29 . 24 agreement 25 with 25 with 28 dysfunction 26 a 28 dysfunction 27 peroxisomal 28 dysfunction in addition , the peroxisomal volume density was increased in the soma of neurons in gyrus frontalis at advanced ad stages . 0 ###LEFT-WALL### 7 density 0 ###LEFT-WALL### 9 increased 0 ###LEFT-WALL### 22 . 1 in 2 addition 1 in 3 , 1 in 7 density 4 the 7 density 5 peroxisomal 6 volume 6 volume 7 density 7 density 8 was 8 was 9 increased 9 increased 10 in 9 increased 15 in 9 increased 18 at 10 in 12 soma 11 the 12 soma 12 soma 13 of 13 of 14 neurons 15 in 17 frontalis 16 gyrus 17 frontalis 18 at 21 stages 19 advanced 21 stages 20 ad 21 stages confocal laser microscopy demonstrated a loss of peroxisomes in neuronal processes with abnormally phosphorylated tau protein , implicating impaired trafficking as the cause of altered peroxisomal distribution . 0 ###LEFT-WALL### 3 microscopy 0 ###LEFT-WALL### 4 demonstrated 1 confocal 3 microscopy 2 laser 3 microscopy 3 microscopy 4 demonstrated 4 demonstrated 6 loss 4 demonstrated 9 in 5 a 6 loss 6 loss 7 of 7 of 8 peroxisomes 9 in 11 processes 10 neuronal 11 processes 11 processes 12 with 11 processes 18 implicating 12 with 16 protein 13 abnormally 14 phosphorylated 14 phosphorylated 15 tau 15 tau 16 protein 17 , 18 implicating 18 implicating 20 trafficking 18 implicating 21 as 18 implicating 28 . 19 impaired 20 trafficking 21 as 23 cause 22 the 23 cause 23 cause 24 of 24 of 27 distribution 25 altered 27 distribution 26 peroxisomal 27 distribution besides the original braak staging , the study design allowed a direct correlation between the biochemical findings and the amount of neurofibrillary tangles ( [nft] [ )(and neuritic plaques , quantified in adjacent tissue sections . 0 ###LEFT-WALL### 9 design 0 ###LEFT-WALL### 10 allowed 0 ###LEFT-WALL### 36 . 1 besides 5 staging 1 besides 6 , 1 besides 9 design 2 the 5 staging 3 original 5 staging 4 braak 5 staging 7 the 9 design 8 study 9 design 9 design 10 allowed 10 allowed 13 correlation 10 allowed 17 findings 10 allowed 18 and 11 a 13 correlation 12 direct 13 correlation 13 correlation 14 between 14 between 16 biochemical 15 the 16 biochemical 18 and 35 sections 19 the 20 amount 20 amount 21 of 20 amount 35 sections 21 of 35 sections 22 neurofibrillary 23 tangles 23 tangles 27 )(and 24 ( 27 )(and 27 )(and 29 plaques 27 )(and 30 , 27 )(and 31 quantified 27 )(and 35 sections 28 neuritic 29 plaques 31 quantified 32 in 32 in 34 tissue 33 adjacent 34 tissue interestingly , the decrease in plasmalogens and the increase in vlcfa and peroxisomal volume density in neuronal somata all showed a stronger association [with] [nft] than with neuritic plaques . 0 ###LEFT-WALL### 7 and 0 ###LEFT-WALL### 20 showed 0 ###LEFT-WALL### 30 . 1 interestingly 2 , 1 interestingly 7 and 3 the 4 decrease 4 decrease 5 in 4 decrease 7 and 5 in 6 plasmalogens 7 and 9 increase 7 and 10 in 7 and 16 in 7 and 20 showed 8 the 9 increase 10 in 12 and 11 vlcfa 12 and 12 and 15 density 13 peroxisomal 14 volume 14 volume 15 density 16 in 18 somata 17 neuronal 18 somata 19 all 20 showed 20 showed 23 association 20 showed 26 than 21 a 23 association 22 stronger 23 association 26 than 27 with 27 with 29 plaques 28 neuritic 29 plaques these results indicate substantial peroxisome - related alterations in ad , which may contribute to the progression of ad pathology . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 indicate 0 ###LEFT-WALL### 7 related 0 ###LEFT-WALL### 11 , 0 ###LEFT-WALL### 21 . 1 these 2 results 2 results 3 indicate 3 indicate 5 peroxisome 4 substantial 5 peroxisome 6 - 7 related 7 related 8 alterations 7 related 9 in 7 related 11 , 9 in 10 ad 11 , 12 which 11 , 14 contribute 12 which 13 may 13 may 14 contribute 14 contribute 15 to 15 to 17 progression 16 the 17 progression 17 progression 18 of 18 of 20 pathology 19 ad 20 pathology a recent editorial entitled " state of aggregation " ( nat . 0 ###LEFT-WALL### 3 editorial 0 ###LEFT-WALL### 4 entitled 1 a 2 recent 1 a 3 editorial 2 recent 3 editorial 3 editorial 4 entitled 4 entitled 5 " 4 entitled 6 state 6 state 7 of 7 of 8 aggregation 8 aggregation 9 " 8 aggregation 11 nat 10 ( 11 nat 11 nat 12 . neurosci . 0 ###LEFT-WALL### 1 neurosci 0 ###LEFT-WALL### 2 . while this is a laudable goal , it is based on the assumption that the neurotoxicity depends upon a specific tertiary structure of the protein aggregates . 0 ###LEFT-WALL### 8 it 0 ###LEFT-WALL### 10 based 0 ###LEFT-WALL### 27 . 1 while 2 this 1 while 3 is 1 while 7 , 1 while 8 it 2 this 3 is 3 is 6 goal 4 a 5 laudable 4 a 6 goal 5 laudable 6 goal 8 it 9 is 9 is 10 based 10 based 11 on 11 on 13 assumption 12 the 13 assumption 13 assumption 14 that 14 that 16 neurotoxicity 14 that 17 depends 15 the 16 neurotoxicity 16 neurotoxicity 17 depends 17 depends 18 upon 18 upon 22 structure 19 a 20 specific 19 a 22 structure 20 specific 22 structure 21 tertiary 22 structure 22 structure 23 of 23 of 26 aggregates 24 the 26 aggregates 25 protein 26 aggregates here , i describe evidence ( not mentioned in the editorial ) that suggests that it is not the protein oligomers , per se , that damage neurons . 0 ###LEFT-WALL### 3 i 0 ###LEFT-WALL### 7 not 0 ###LEFT-WALL### 29 . 1 here 2 , 1 here 3 i 3 i 4 describe 4 describe 5 evidence 6 ( 7 not 7 not 13 that 7 not 14 suggests 8 mentioned 9 in 8 mentioned 12 ) 8 mentioned 13 that 9 in 11 editorial 10 the 11 editorial 13 that 14 suggests 14 suggests 15 that 15 that 16 it 15 that 17 is 16 it 17 is 17 is 18 not 17 is 21 oligomers 17 is 24 se 17 is 26 that 19 the 21 oligomers 20 protein 21 oligomers 22 , 24 se 23 per 24 se 24 se 25 , 26 that 27 damage 26 that 28 neurons 27 damage 28 neurons instead , neurons are damaged by an unseen sequence ( [s] [ )(of chemical reactions that generate reactive oxygen species ( ros ) , and it is the ros that cause both protein aggregation and neurotoxicity . 0 ###LEFT-WALL### 3 neurons 0 ###LEFT-WALL### 5 damaged 0 ###LEFT-WALL### 25 and 0 ###LEFT-WALL### 37 . 1 instead 2 , 1 instead 3 neurons 3 neurons 4 are 4 are 5 damaged 5 damaged 6 by 6 by 9 sequence 7 an 8 unseen 7 an 9 sequence 8 unseen 9 sequence 9 sequence 13 )(of 10 ( 13 )(of 13 )(of 15 reactions 13 )(of 24 , 14 chemical 15 reactions 15 reactions 16 that 15 reactions 17 generate 15 reactions 22 ros 16 that 17 generate 17 generate 20 species 18 reactive 19 oxygen 19 oxygen 20 species 21 ( 22 ros 22 ros 23 ) 24 , 25 and 25 and 26 it 25 and 27 is 26 it 27 is 27 is 29 ros 28 the 29 ros 29 ros 30 that 29 ros 31 cause 30 that 31 cause 31 cause 35 and 32 both 35 and 33 protein 34 aggregation 34 aggregation 35 and 35 and 36 neurotoxicity the latter " proteooxidotoxicity " mechanism provides an explanation for numerous findings in the field of neurodegenerative disorders , including the inability to identify specific receptors for the pathogenic proteins . 0 ###LEFT-WALL### 6 mechanism 0 ###LEFT-WALL### 7 provides 1 the 6 mechanism 2 latter 3 " 2 latter 6 mechanism 4 proteooxidotoxicity 5 " 4 proteooxidotoxicity 6 mechanism 6 mechanism 7 provides 7 provides 9 explanation 7 provides 13 in 8 an 9 explanation 9 explanation 10 for 10 for 12 findings 11 numerous 12 findings 13 in 15 field 14 the 15 field 15 field 16 of 15 field 20 including 16 of 18 disorders 17 neurodegenerative 18 disorders 19 , 20 including 20 including 22 inability 20 including 27 for 20 including 31 . 21 the 22 inability 22 inability 23 to 22 inability 24 identify 23 to 24 identify 24 identify 26 receptors 25 specific 26 receptors 27 for 30 proteins 28 the 30 proteins 29 pathogenic 30 proteins objectives : we evaluated anthropometric parameters and physical fitness in elderly japanese . 0 ###LEFT-WALL### 1 objectives 0 ###LEFT-WALL### 2 : 2 : 3 we 2 : 4 evaluated 2 : 13 . 3 we 4 evaluated 4 evaluated 7 and 4 evaluated 10 in 5 anthropometric 6 parameters 6 parameters 7 and 7 and 9 fitness 8 physical 9 fitness 10 in 12 japanese 11 elderly 12 japanese methods : a total of 2,106 elderly japanese ( 749 men and 1,357 women ) , aged 60 - 79 years , were enrolled in a cross - sectional investigation study . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 16 , 1 methods 2 : 2 : 4 total 3 a 4 total 4 total 5 of 5 of 8 japanese 6 2,106 8 japanese 7 elderly 8 japanese 8 japanese 12 and 9 ( 12 and 10 749 11 men 11 men 12 and 12 and 14 women 12 and 15 ) 13 1,357 14 women 16 , 22 , 17 aged 21 years 17 aged 22 , 18 60 19 - 19 - 20 79 19 - 21 years 22 , 23 were 23 were 24 enrolled 24 enrolled 25 in 25 in 27 cross 26 a 27 cross 27 cross 31 study 28 - 31 study 29 sectional 30 investigation 30 investigation 31 study 31 study 32 . anthropometric parameters and physical fitness , i.e [.] , muscle strength and flexibility , were measured . 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 15 were 0 ###LEFT-WALL### 17 . 1 anthropometric 2 parameters 2 parameters 3 and 3 and 5 fitness 3 and 6 , 4 physical 5 fitness 6 , 11 strength 6 , 12 and 7 i.e 9 , 7 i.e 10 muscle 10 muscle 11 strength 12 and 13 flexibility 12 and 14 , 12 and 15 were 15 were 16 measured of the 2,106 subjects , 569 subjects ( 302 men and 267 women ) were further evaluated for aerobic exercise level , using the ventilatory threshold ( vt ) . 0 ###LEFT-WALL### 7 subjects 0 ###LEFT-WALL### 17 evaluated 0 ###LEFT-WALL### 30 . 1 of 4 subjects 1 of 5 , 1 of 7 subjects 2 the 3 2,106 3 2,106 4 subjects 6 569 7 subjects 7 subjects 11 and 7 subjects 15 were 8 ( 11 and 9 302 10 men 10 men 11 and 11 and 13 women 11 and 14 ) 12 267 13 women 15 were 17 evaluated 16 further 17 evaluated 17 evaluated 18 for 18 for 21 level 19 aerobic 21 level 20 exercise 21 level 21 level 23 using 22 , 23 using 23 using 26 threshold 23 using 29 ) 24 the 26 threshold 25 ventilatory 26 threshold 26 threshold 28 vt 27 ( 28 vt 28 vt 29 ) results : muscle strength in subjects in their 70 [s] was significantly lower than that in subjects in their 60 [s] in both sexes . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 25 . 2 : 4 strength 2 : 11 was 3 muscle 4 strength 4 strength 5 in 4 strength 7 in 4 strength 11 was 5 in 6 subjects 7 in 9 70 8 their 9 70 11 was 12 significantly 11 was 13 lower 13 lower 14 than 13 lower 16 in 13 lower 18 in 14 than 15 that 16 in 17 subjects 18 in 20 60 19 their 20 60 20 60 22 in 22 in 24 sexes 23 both 24 sexes two hundred and twenty - nine men ( 30.6 [%] [ )(and 540 women ( 39.8 % ) were taking no medications . 0 ###LEFT-WALL### 4 twenty 0 ###LEFT-WALL### 19 were 0 ###LEFT-WALL### 23 . 1 two 2 hundred 2 hundred 3 and 3 and 4 twenty 4 twenty 7 men 4 twenty 19 were 5 - 7 men 6 nine 7 men 7 men 14 women 7 men 18 ) 8 ( 14 women 9 30.6 12 )(and 12 )(and 13 540 12 )(and 14 women 14 women 17 % 14 women 18 ) 15 ( 17 % 16 39.8 17 % 17 % 18 ) 19 were 20 taking 20 taking 22 medications 21 no 22 medications in men , anthropometric parameters were significantly lower and muscle strength , flexibility , and work rate at vt were significantly higher in subjects without medications than these values in subjects with medications . 0 ###LEFT-WALL### 5 parameters 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 12 , 0 ###LEFT-WALL### 34 . 1 in 2 men 1 in 3 , 1 in 5 parameters 4 anthropometric 5 parameters 5 parameters 9 and 6 were 8 lower 6 were 9 and 7 significantly 8 lower 9 and 10 muscle 10 muscle 11 strength 12 , 15 and 12 , 20 were 13 flexibility 15 and 14 , 15 and 15 and 17 rate 15 and 18 at 15 and 20 were 16 work 17 rate 18 at 19 vt 20 were 21 significantly 20 were 22 higher 22 higher 23 in 22 higher 25 without 22 higher 27 than 22 higher 30 in 22 higher 32 with 23 in 24 subjects 25 without 26 medications 27 than 29 values 28 these 29 values 30 in 31 subjects 32 with 33 medications in women , body weight , body mass index [(] bmi [ )(, and abdominal circumference were significantly lower , and muscle strength was significantly higher in subjects without medications than these values in subjects with medications . 0 ###LEFT-WALL### 14 and 0 ###LEFT-WALL### 17 were 0 ###LEFT-WALL### 21 and 0 ###LEFT-WALL### 38 . 1 in 2 women 1 in 14 and 2 women 5 weight 3 , 5 weight 4 body 5 weight 5 weight 6 , 7 body 8 mass 8 mass 11 bmi 9 index 11 bmi 11 bmi 14 and 13 )(, 14 and 14 and 16 circumference 14 and 17 were 15 abdominal 16 circumference 17 were 18 significantly 17 were 19 lower 20 , 21 and 21 and 23 strength 21 and 24 was 22 muscle 23 strength 23 strength 24 was 24 was 25 significantly 24 was 26 higher 26 higher 27 in 26 higher 29 without 26 higher 31 than 26 higher 34 in 27 in 28 subjects 29 without 30 medications 31 than 33 values 32 these 33 values 34 in 35 subjects 35 subjects 36 with 36 with 37 medications conclusion : this mean value may provide a useful database for evaluating anthropometric parameters and physical fitness in elderly japanese subjects . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 5 value 2 : 7 provide 2 : 22 . 3 this 4 mean 4 mean 5 value 5 value 6 may 6 may 7 provide 7 provide 10 database 7 provide 11 for 8 a 10 database 9 useful 10 database 11 for 12 evaluating 12 evaluating 15 and 12 evaluating 18 in 13 anthropometric 14 parameters 14 parameters 15 and 15 and 17 fitness 16 physical 17 fitness 18 in 21 subjects 19 elderly 21 subjects 20 japanese 21 subjects purpose : since adhesion of the restorative materials to pre - polymerized or aged resin composites presents a challenge to the clinicians , existing restorations are often removed and remade prior to cementation of fixed dental prostheses ( fdps ) . 0 ###LEFT-WALL### 1 purpose 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 41 . 2 : 13 or 3 since 4 adhesion 3 since 11 - 3 since 13 or 4 adhesion 5 of 4 adhesion 9 to 5 of 8 materials 6 the 8 materials 7 restorative 8 materials 9 to 10 pre 12 polymerized 13 or 13 or 14 aged 14 aged 15 resin 15 resin 16 composites 15 resin 30 remade 16 composites 23 , 17 presents 19 challenge 17 presents 20 to 17 presents 23 , 18 a 19 challenge 20 to 22 clinicians 21 the 22 clinicians 23 , 29 and 24 existing 25 restorations 25 restorations 26 are 26 are 29 and 27 often 28 removed 28 removed 29 and 29 and 30 remade 30 remade 32 to 31 prior 32 to 32 to 33 cementation 33 cementation 34 of 33 cementation 39 fdps 34 of 37 prostheses 35 fixed 37 prostheses 36 dental 37 prostheses 38 ( 39 fdps 39 fdps 40 ) this study evaluated bond strength of [non] [-] aged and aged resin composite to an indirect resin composite and pressed glass ceramic using two resin cements . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 26 cements 0 ###LEFT-WALL### 27 . 1 this 2 study 2 study 19 and 3 evaluated 5 strength 3 evaluated 19 and 4 bond 5 strength 5 strength 6 of 5 strength 13 composite 6 of 10 and 9 aged 10 and 10 and 11 aged 11 aged 12 resin 13 composite 14 to 14 to 18 composite 15 an 16 indirect 15 an 18 composite 16 indirect 18 composite 17 resin 18 composite 19 and 20 pressed 20 pressed 22 ceramic 20 pressed 23 using 21 glass 22 ceramic 23 using 24 two 24 two 25 resin 24 two 26 cements 25 resin 26 cements materials and methods : disk - shaped specimens ( diameter [:] 3.5 , thickness : 3 mm [ )(( n = 160 ) produced from a microhybrid resin composite ( quadrant anterior shine ) were randomly divided [into] eight groups . 0 ###LEFT-WALL### 3 methods 0 ###LEFT-WALL### 4 : 0 ###LEFT-WALL### 13 , 0 ###LEFT-WALL### 35 were 0 ###LEFT-WALL### 41 . 1 materials 2 and 2 and 3 methods 3 methods 4 : 4 : 5 disk 5 disk 8 specimens 6 - 8 specimens 7 shaped 8 specimens 8 specimens 10 diameter 8 specimens 13 , 9 ( 10 diameter 10 diameter 12 3.5 10 diameter 13 , 13 , 14 thickness 13 , 35 were 14 thickness 15 : 15 : 21 = 15 : 24 produced 16 3 17 mm 17 mm 21 = 19 )(( 21 = 20 n 21 = 21 = 22 160 21 = 23 ) 24 produced 25 from 25 from 29 composite 26 a 27 microhybrid 26 a 29 composite 27 microhybrid 29 composite 28 resin 29 composite 29 composite 33 shine 30 ( 33 shine 31 quadrant 32 anterior 32 anterior 33 shine 33 shine 34 ) 35 were 40 groups 36 randomly 37 divided 37 divided 40 groups 39 eight 40 groups while half of the specimens were kept dry at 37 °c for 24 h , the other half was aged by means of thermocycling ( 6000 times , 5 °c to 55 °c ) . 0 ###LEFT-WALL### 18 half 0 ###LEFT-WALL### 19 was 0 ###LEFT-WALL### 35 . 1 while 2 half 1 while 7 kept 1 while 15 , 1 while 18 half 2 half 3 of 2 half 6 were 3 of 5 specimens 4 the 5 specimens 6 were 7 kept 7 kept 8 dry 8 dry 9 at 9 at 11 °c 10 37 11 °c 11 °c 12 for 12 for 14 h 13 24 14 h 16 the 17 other 17 other 18 half 18 half 19 was 19 was 20 aged 20 aged 21 by 21 by 22 means 22 means 23 of 23 of 24 thermocycling 24 thermocycling 27 times 24 thermocycling 31 to 25 ( 27 times 26 6000 27 times 27 times 28 , 28 , 31 to 29 5 30 °c 30 °c 31 to 31 to 33 °c 31 to 34 ) 32 55 33 °c the [non] [-] aged and aged resin composites were bonded to a highly filled indirect composite ( estenia ) and [a] pressed glass ceramic ( ips empress ii ) using either [a] photopolymerizing ( variolink veneer ) or [a] dual - polymerizing ( panavia f2.0 ) resin cement . 0 ###LEFT-WALL### 48 cement 0 ###LEFT-WALL### 49 . 1 the 8 composites 4 aged 5 and 5 and 6 aged 5 and 7 resin 7 resin 8 composites 8 composites 20 and 8 composites 38 or 9 were 10 bonded 9 were 20 and 10 bonded 11 to 11 to 16 composite 12 a 13 highly 12 a 16 composite 13 highly 14 filled 15 indirect 16 composite 16 composite 18 estenia 17 ( 18 estenia 18 estenia 19 ) 20 and 22 pressed 20 and 30 using 22 pressed 24 ceramic 23 glass 24 ceramic 24 ceramic 27 empress 25 ( 27 empress 26 ips 27 empress 27 empress 28 ii 27 empress 29 ) 30 using 31 either 30 using 33 photopolymerizing 33 photopolymerizing 36 veneer 34 ( 36 veneer 35 variolink 36 veneer 36 veneer 37 ) 38 or 42 polymerizing 38 or 45 f2.0 38 or 47 resin 40 dual 41 - 40 dual 42 polymerizing 43 ( 45 f2.0 44 panavia 45 f2.0 45 f2.0 46 ) 47 resin 48 cement while cementation surfaces of both the direct and indirect composite materials were silica coated ( 30 µm sio2 , cojet - sand ) and silanized ( espe - sil ) , ceramic surfaces were conditioned with hydrofluoric acid ( 20 s ) , neutralized , and silanized prior to cementation . 0 ###LEFT-WALL### 11 materials 0 ###LEFT-WALL### 24 and 0 ###LEFT-WALL### 31 , 0 ###LEFT-WALL### 51 . 1 while 3 surfaces 1 while 11 materials 2 cementation 3 surfaces 3 surfaces 4 of 4 of 5 both 6 the 11 materials 7 direct 8 and 8 and 9 indirect 8 and 11 materials 10 composite 11 materials 11 materials 24 and 12 were 13 silica 12 were 24 and 13 silica 14 coated 13 silica 18 sio2 15 ( 18 sio2 16 30 18 sio2 17 µm 18 sio2 18 sio2 20 cojet 18 sio2 23 ) 19 , 20 cojet 20 cojet 22 sand 20 cojet 23 ) 21 - 22 sand 22 sand 23 ) 24 and 25 silanized 25 silanized 28 - 26 ( 28 - 27 espe 28 - 28 - 29 sil 28 - 30 ) 31 , 33 surfaces 31 , 46 and 32 ceramic 33 surfaces 33 surfaces 46 and 34 were 35 conditioned 34 were 46 and 35 conditioned 36 with 35 conditioned 44 neutralized 36 with 38 acid 37 hydrofluoric 38 acid 38 acid 41 s 39 ( 41 s 40 20 41 s 41 s 42 ) 43 , 44 neutralized 44 neutralized 45 , 45 , 46 and 46 and 47 silanized 47 silanized 49 to 48 prior 49 to 49 to 50 cementation all specimens were cemented under a load of 750 g . 0 ###LEFT-WALL### 2 specimens 0 ###LEFT-WALL### 4 cemented 0 ###LEFT-WALL### 11 . 1 all 2 specimens 2 specimens 3 were 3 were 4 cemented 4 cemented 5 under 5 under 7 load 6 a 7 load 7 load 8 of 8 of 10 g 9 750 10 g shear force [was] applied to the adhesive interface in a universal testing machine ( 1 mm/min ) . 0 ###LEFT-WALL### 1 shear 0 ###LEFT-WALL### 18 . 1 shear 2 force 2 force 4 applied 4 applied 5 to 4 applied 9 in 5 to 8 interface 6 the 8 interface 7 adhesive 8 interface 9 in 13 machine 10 a 13 machine 11 universal 12 testing 12 testing 13 machine 13 machine 16 mm/min 14 ( 16 mm/min 15 1 16 mm/min 16 mm/min 17 ) failure types of the specimens were identified after debonding . 0 ###LEFT-WALL### 2 types 0 ###LEFT-WALL### 7 identified 0 ###LEFT-WALL### 10 . 1 failure 2 types 2 types 3 of 2 types 6 were 3 of 5 specimens 4 the 5 specimens 6 were 7 identified 7 identified 8 after 8 after 9 debonding results : significant effects of aging ( p < 0.05 ) , restorative material ( p < 0.05 ) , and cement type ( p < 0.05 ) were observed on the bond strength ( 3 - way anova ) . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 41 . 2 : 21 and 2 : 30 observed 3 significant 4 effects 4 effects 5 of 4 effects 21 and 5 of 6 aging 6 aging 9 < 6 aging 14 material 7 ( 9 < 8 p 9 < 9 < 10 0.05 9 < 11 ) 12 , 14 material 13 restorative 14 material 14 material 17 < 14 material 19 ) 15 ( 17 < 16 p 17 < 17 < 18 0.05 17 < 19 ) 20 , 21 and 21 and 23 type 21 and 26 < 21 and 29 were 22 cement 23 type 24 ( 26 < 25 p 26 < 26 < 27 0.05 26 < 28 ) 29 were 30 observed 30 observed 31 on 30 observed 37 - 31 on 34 strength 32 the 34 strength 33 bond 34 strength 35 ( 37 - 36 3 37 - 37 - 39 anova 37 - 40 ) 38 way 39 anova interaction terms were also significant ( p < 0.05 [ )(( tukey 's test ) . 0 ###LEFT-WALL### 2 terms 0 ###LEFT-WALL### 3 were 0 ###LEFT-WALL### 16 . 1 interaction 2 terms 2 terms 3 were 3 were 4 also 3 were 5 significant 5 significant 8 < 6 ( 8 < 7 p 8 < 8 < 9 0.05 9 0.05 14 test 11 )(( 14 test 12 tukey 13 's 13 's 14 test 14 test 15 ) after aging , in terms of bond strength , indirect composite and pressed glass ceramic [in] combination with both [cements] showed no significant difference ( p > 0.05 ) . 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 21 showed 0 ###LEFT-WALL### 30 . 1 after 2 aging 1 after 3 , 1 after 12 and 4 in 5 terms 4 in 12 and 5 terms 6 of 6 of 7 bond 8 strength 9 , 9 , 11 composite 9 , 12 and 10 indirect 11 composite 12 and 17 combination 12 and 18 with 12 and 21 showed 13 pressed 14 glass 14 glass 17 combination 15 ceramic 17 combination 18 with 19 both 21 showed 24 difference 22 no 24 difference 23 significant 24 difference 24 difference 27 > 25 ( 27 > 26 p 27 > 27 > 28 0.05 27 > 29 ) both indirect composite ( 24.3 ± 5.1 [mpa] ) [and] glass ceramic in combination [with] variolink ( 22 ± 9 mpa ) showed the highest results on [non] - aged [composites] , but were not significantly different from one another ( p > 0.05 ) . 0 ###LEFT-WALL### 12 ceramic 0 ###LEFT-WALL### 33 but 0 ###LEFT-WALL### 46 . 1 both 2 indirect 2 indirect 11 glass 3 composite 6 ± 3 composite 9 ) 3 composite 11 glass 4 ( 6 ± 5 24.3 6 ± 6 ± 7 5.1 6 ± 9 ) 11 glass 12 ceramic 12 ceramic 13 in 12 ceramic 33 but 13 in 16 variolink 14 combination 16 variolink 16 variolink 21 mpa 17 ( 21 mpa 18 22 21 mpa 19 ± 21 mpa 20 9 21 mpa 21 mpa 22 ) 23 showed 26 results 23 showed 27 on 23 showed 30 aged 23 showed 33 but 24 the 25 highest 24 the 26 results 29 - 30 aged 30 aged 32 , 33 but 34 were 34 were 35 not 34 were 37 different 36 significantly 37 different 37 different 38 from 37 different 43 > 38 from 40 another 39 one 40 another 41 ( 43 > 42 p 43 > 43 > 44 0.05 43 > 45 ) conclusion : regardless of the resin cement type , considering the bond values and the failure types , the adhesion quality of indirect composite cemented [to] [non] - aged and aged resin composite was superior with both [cements] compared to that of pressed glass ceramic . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 8 type 3 regardless 4 of 4 of 7 cement 4 of 8 type 5 the 7 cement 6 resin 7 cement 8 type 10 considering 9 , 10 considering 10 considering 14 and 10 considering 21 quality 11 the 13 values 12 bond 13 values 13 values 14 and 14 and 17 types 14 and 18 , 15 the 17 types 16 failure 17 types 19 the 21 quality 20 adhesion 21 quality 21 quality 22 of 22 of 24 composite 23 indirect 24 composite 24 composite 25 cemented 24 composite 35 superior 28 - 35 superior 29 aged 30 and 30 and 32 resin 30 and 33 composite 30 and 34 was 30 and 35 superior 31 aged 32 resin 33 composite 34 was 35 superior 36 with 35 superior 42 of 35 superior 46 . 36 with 37 both 37 both 39 compared 39 compared 40 to 40 to 41 that 42 of 45 ceramic 43 pressed 45 ceramic 44 glass 45 ceramic purpose : zirconia - based ceramics offer strong restorations in dentistry , but the adhesive bond strength of resin cements [to] [such] [ceramics] is not optimal . 0 ###LEFT-WALL### 1 purpose 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 13 but 0 ###LEFT-WALL### 27 . 1 purpose 2 : 2 : 3 zirconia 3 zirconia 9 restorations 4 - 9 restorations 5 based 6 ceramics 6 ceramics 9 restorations 7 offer 9 restorations 8 strong 9 restorations 9 restorations 10 in 9 restorations 12 , 10 in 11 dentistry 13 but 16 bond 13 but 24 is 14 the 16 bond 15 adhesive 16 bond 16 bond 17 strength 16 bond 20 cements 16 bond 24 is 17 strength 18 of 17 strength 20 cements 18 of 19 resin 24 is 25 not 24 is 26 optimal 25 not 26 optimal this study evaluated the bond strength of silane/adhesive/resin cement and zirconia primer/resin cement combinations on [non] - glazed and glazed zirconia surfaces before and after aging . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 evaluated 0 ###LEFT-WALL### 17 - 0 ###LEFT-WALL### 27 . 1 this 2 study 2 study 3 evaluated 3 evaluated 6 strength 4 the 6 strength 5 bond 6 strength 6 strength 7 of 7 of 8 silane/adhesive/resin 8 silane/adhesive/resin 10 and 8 silane/adhesive/resin 15 on 9 cement 10 and 10 and 12 primer/resin 10 and 13 cement 11 zirconia 12 primer/resin 13 cement 14 combinations 13 cement 15 on 17 - 19 and 18 glazed 19 and 19 and 20 glazed 20 glazed 22 surfaces 21 zirconia 22 surfaces 22 surfaces 24 and 23 before 24 and 24 and 25 after 25 after 26 aging materials and methods : disk - shaped zirconia ceramic specimens ( diameter [:] 8 mm [;] thickness [:] 2 mm [ )(( n = 80 , n = 10 per group ) were randomly divided into 2 groups . 0 ###LEFT-WALL### 3 methods 0 ###LEFT-WALL### 4 : 0 ###LEFT-WALL### 6 - 0 ###LEFT-WALL### 39 . 1 materials 2 and 2 and 3 methods 3 methods 4 : 4 : 5 disk 6 - 10 specimens 6 - 35 divided 7 shaped 9 ceramic 8 zirconia 9 ceramic 9 ceramic 10 specimens 10 specimens 17 thickness 10 specimens 33 were 11 ( 17 thickness 12 diameter 17 thickness 14 8 15 mm 15 mm 17 thickness 17 thickness 24 = 17 thickness 28 = 17 thickness 32 ) 19 2 20 mm 20 mm 24 = 22 )(( 24 = 23 n 24 = 24 = 25 80 24 = 26 , 26 , 28 = 27 n 28 = 28 = 29 10 29 10 30 per 30 per 31 group 33 were 34 randomly 33 were 35 divided 35 divided 36 into 36 into 38 groups 37 2 38 groups while half of the specimens received one coat of glaze and were later finished by grinding , the other half was only ground using 1200 - grit silicone carbide abrasives under water . 0 ###LEFT-WALL### 27 grit 0 ###LEFT-WALL### 33 . 1 while 2 half 1 while 11 and 1 while 26 - 1 while 27 grit 2 half 3 of 2 half 11 and 3 of 5 specimens 4 the 5 specimens 6 received 8 coat 6 received 11 and 7 one 8 coat 8 coat 9 of 9 of 10 glaze 11 and 17 , 12 were 14 finished 12 were 17 , 13 later 14 finished 14 finished 15 by 15 by 16 grinding 17 , 23 ground 18 the 19 other 19 other 20 half 20 half 21 was 21 was 23 ground 22 only 23 ground 23 ground 24 using 24 using 25 1200 27 grit 30 abrasives 27 grit 31 under 28 silicone 29 carbide 29 carbide 30 abrasives 31 under 32 water the glazed specimens were then conditioned with 9.5 % hf acid gel for 60 s , rinsed with water for 90 s , and neutralized . 0 ###LEFT-WALL### 3 specimens 0 ###LEFT-WALL### 24 and 0 ###LEFT-WALL### 26 . 1 the 3 specimens 2 glazed 3 specimens 3 specimens 24 and 4 were 5 then 4 were 6 conditioned 4 were 24 and 6 conditioned 7 with 7 with 12 gel 8 9.5 9 % 9 % 11 acid 10 hf 11 acid 11 acid 12 gel 12 gel 13 for 12 gel 17 rinsed 13 for 15 s 14 60 15 s 16 , 17 rinsed 17 rinsed 18 with 17 rinsed 23 , 18 with 19 water 19 water 20 for 20 for 22 s 21 90 22 s 24 and 25 neutralized [the] glazed [and] [non] - glazed specimens were further divided into two groups . 0 ###LEFT-WALL### 7 specimens 0 ###LEFT-WALL### 10 divided 0 ###LEFT-WALL### 14 . 2 glazed 5 - 2 glazed 7 specimens 6 glazed 7 specimens 7 specimens 8 were 8 were 9 further 8 were 10 divided 10 divided 11 into 11 into 13 groups 12 two 13 groups two resin cements , namely , variolink ii and multilink automix were adhered onto the zirconia surfaces with their corresponding adhesive systems . 0 ###LEFT-WALL### 2 resin 0 ###LEFT-WALL### 3 cements 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 23 . 1 two 2 resin 2 resin 3 cements 3 cements 5 namely 3 cements 7 variolink 4 , 5 namely 5 namely 6 , 7 variolink 8 ii 9 and 10 multilink 9 and 13 adhered 10 multilink 11 automix 10 multilink 12 were 10 multilink 13 adhered 11 automix 12 were 13 adhered 14 onto 13 adhered 18 with 14 onto 17 surfaces 15 the 17 surfaces 16 zirconia 17 surfaces 18 with 22 systems 19 their 22 systems 20 corresponding 22 systems 21 adhesive 22 systems in the variolink ii group , zirconia surfaces were silanized ( monobond - s ) , and adhesive resin ( heliobond ) was applied and photopolymerized . 0 ###LEFT-WALL### 8 surfaces 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 27 . 1 in 5 group 1 in 6 , 1 in 8 surfaces 2 the 5 group 3 variolink 4 ii 3 variolink 5 group 7 zirconia 8 surfaces 8 surfaces 17 and 9 were 10 silanized 9 were 17 and 10 silanized 13 - 11 ( 13 - 12 monobond 13 - 13 - 14 s 13 - 15 ) 16 , 17 and 17 and 25 and 18 adhesive 19 resin 19 resin 21 heliobond 19 resin 23 was 20 ( 21 heliobond 21 heliobond 22 ) 23 was 25 and 24 applied 25 and 25 and 26 photopolymerized in the multilink automix group , one coat of metal/zirconia primer was applied with a microbrush , left to react for 180 s , and dried using oil - free air . 0 ###LEFT-WALL### 8 coat 0 ###LEFT-WALL### 25 and 0 ###LEFT-WALL### 29 - 1 in 5 group 1 in 6 , 1 in 8 coat 2 the 5 group 3 multilink 4 automix 4 automix 5 group 7 one 8 coat 8 coat 9 of 8 coat 25 and 9 of 11 primer 10 metal/zirconia 11 primer 12 was 13 applied 12 was 25 and 13 applied 14 with 14 with 16 microbrush 15 a 16 microbrush 16 microbrush 18 left 17 , 18 left 18 left 19 to 18 left 24 , 19 to 20 react 20 react 21 for 21 for 23 s 22 180 23 s 25 and 26 dried 25 and 27 using 27 using 28 oil 29 - 30 free 29 - 32 . 30 free 31 air half of the specimens in each cement group were subjected to 5000 [thermocycles] ( 5 °c to 55 °c ) and the other half was kept in the dark for 24 h at 37 °c prior to testing . 0 ###LEFT-WALL### 1 half 0 ###LEFT-WALL### 10 subjected 0 ###LEFT-WALL### 21 and 0 ###LEFT-WALL### 39 . 1 half 2 of 1 half 9 were 2 of 4 specimens 3 the 4 specimens 4 specimens 5 in 5 in 8 group 6 each 8 group 7 cement 8 group 9 were 10 subjected 10 subjected 11 to 11 to 12 5000 12 5000 17 to 14 ( 17 to 15 5 16 °c 16 °c 17 to 17 to 19 °c 17 to 20 ) 18 55 19 °c 21 and 24 half 21 and 26 kept 22 the 23 other 23 other 24 half 24 half 25 was 25 was 26 kept 26 kept 27 in 26 kept 30 for 26 kept 33 at 26 kept 37 to 27 in 29 dark 28 the 29 dark 30 for 32 h 31 24 32 h 33 at 35 °c 34 37 35 °c 36 prior 37 to 37 to 38 testing specimens were mounted in the jig of the universal testing machine , and force [was] applied to the ceramic/cement interface until failure occurred ( 1 mm/min ) . 0 ###LEFT-WALL### 1 specimens 0 ###LEFT-WALL### 3 mounted 0 ###LEFT-WALL### 28 . 1 specimens 2 were 2 were 3 mounted 3 mounted 4 in 4 in 6 jig 5 the 6 jig 6 jig 7 of 7 of 13 and 8 the 11 machine 9 universal 10 testing 10 testing 11 machine 11 machine 13 and 12 , 13 and 13 and 14 force 13 and 16 applied 13 and 26 mm/min 16 applied 17 to 16 applied 21 until 17 to 20 interface 18 the 20 interface 19 ceramic/cement 20 interface 21 until 22 failure 21 until 23 occurred 22 failure 23 occurred 24 ( 26 mm/min 25 1 26 mm/min 26 mm/min 27 ) after evaluating all debonded specimens under sem , the failure types were defined as either " adhesive " with no cement left on the zirconia ( score 0 ) or " mixed " with less than half of the cement left on the surface with no cohesive failure of the substrate ( score 1 ) . 0 ###LEFT-WALL### 11 types 0 ###LEFT-WALL### 30 or 0 ###LEFT-WALL### 56 . 1 after 2 evaluating 1 after 8 , 1 after 11 types 2 evaluating 3 all 2 evaluating 4 debonded 3 all 4 debonded 4 debonded 5 specimens 5 specimens 6 under 6 under 7 sem 9 the 11 types 10 failure 11 types 11 types 30 or 12 were 13 defined 12 were 30 or 13 defined 14 as 13 defined 19 with 14 as 17 adhesive 15 either 16 " 15 either 17 adhesive 17 adhesive 18 " 19 with 21 cement 19 with 25 zirconia 20 no 21 cement 21 cement 22 left 22 left 23 on 24 the 25 zirconia 25 zirconia 27 score 26 ( 27 score 27 score 28 0 27 score 29 ) 30 or 31 " 30 or 32 mixed 30 or 34 with 30 or 36 than 30 or 48 failure 32 mixed 33 " 34 with 35 less 36 than 37 half 36 than 45 with 37 half 38 of 37 half 41 left 38 of 40 cement 39 the 40 cement 41 left 42 on 41 left 44 surface 41 left 45 with 43 the 44 surface 46 no 48 failure 47 cohesive 48 failure 48 failure 49 of 49 of 51 substrate 50 the 51 substrate 51 substrate 53 score 52 ( 53 score 53 score 54 1 53 score 55 ) data were analyzed using three - way anova and dunnett - t3 post - [hoc] tests . 0 ###LEFT-WALL### 1 data 0 ###LEFT-WALL### 3 analyzed 1 data 2 were 2 were 3 analyzed 3 analyzed 4 using 4 using 5 three 5 three 9 and 6 - 9 and 7 way 8 anova 8 anova 9 and 9 and 10 dunnett 9 and 13 post 9 and 16 tests 9 and 17 . 11 - 13 post 12 t3 13 post 13 post 14 - 14 - 16 tests 16 tests 17 . results : application of a glaze layer significantly improved the bond strength in the silane/adhesive/variolink [ii] group ( p < 0.05 ) , but no significant effect was found in the zirconia primer/multilink automix group ( p > 0.05 ) ( three - way anova ) . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 3 application 2 : 9 improved 2 : 24 but 2 : 47 . 3 application 4 of 3 application 9 improved 4 of 7 layer 5 a 6 glaze 5 a 7 layer 6 glaze 7 layer 8 significantly 9 improved 9 improved 12 strength 9 improved 13 in 10 the 12 strength 11 bond 12 strength 13 in 17 group 14 the 17 group 15 silane/adhesive/variolink 17 group 17 group 20 < 18 ( 20 < 19 p 20 < 20 < 21 0.05 20 < 22 ) 23 , 24 but 24 but 27 effect 24 but 29 found 25 no 27 effect 26 significant 27 effect 27 effect 28 was 28 was 29 found 29 found 30 in 30 in 35 group 31 the 35 group 32 zirconia 35 group 33 primer/multilink 35 group 34 automix 35 group 35 group 38 > 35 group 42 three 35 group 45 anova 36 ( 38 > 37 p 38 > 38 > 39 0.05 38 > 40 ) 41 ( 42 three 42 three 43 - 43 - 45 anova 44 way 45 anova 45 anova 46 ) interaction terms were also significant ( p < 0.05 ) ( dunnett - t3 ) . 0 ###LEFT-WALL### 2 terms 0 ###LEFT-WALL### 3 were 0 ###LEFT-WALL### 16 . 1 interaction 2 terms 2 terms 3 were 3 were 4 also 3 were 5 significant 5 significant 8 < 5 significant 13 - 6 ( 8 < 7 p 8 < 8 < 9 0.05 8 < 10 ) 11 ( 13 - 12 dunnett 13 - 13 - 14 t3 13 - 15 ) thermocycling did not decrease the results significantly in any of the groups ( p > 0.05 ) . 0 ###LEFT-WALL### 1 thermocycling 0 ###LEFT-WALL### 4 decrease 0 ###LEFT-WALL### 18 . 1 thermocycling 2 did 2 did 3 not 2 did 4 decrease 4 decrease 6 results 4 decrease 7 significantly 4 decrease 8 in 5 the 6 results 8 in 9 any 9 any 10 of 10 of 12 groups 11 the 12 groups 12 groups 15 > 13 ( 15 > 14 p 15 > 15 > 16 0.05 15 > 17 ) failure analysis revealed exclusively adhesive failures ( score 0 : 40 out of 40 [ )(in [the] [non] - glazed groups , but predominantly mixed failures ( score 1 : 34 out of 40 [ )(in the glazed groups . 0 ###LEFT-WALL### 2 analysis 0 ###LEFT-WALL### 3 revealed 0 ###LEFT-WALL### 10 : 0 ###LEFT-WALL### 40 . 1 failure 2 analysis 2 analysis 3 revealed 3 revealed 6 failures 4 exclusively 5 adhesive 5 adhesive 6 failures 6 failures 8 score 7 ( 8 score 8 score 9 0 8 score 10 : 10 : 11 40 10 : 30 : 11 40 13 of 11 40 21 groups 11 40 23 but 12 out 13 of 13 of 16 )(in 14 40 16 )(in 19 - 21 groups 20 glazed 21 groups 21 groups 22 , 22 , 23 but 23 but 26 failures 23 but 30 : 24 predominantly 25 mixed 25 mixed 26 failures 26 failures 28 score 27 ( 28 score 28 score 29 1 28 score 30 : 30 : 31 34 31 34 33 of 32 out 33 of 33 of 34 40 34 40 36 )(in 36 )(in 39 groups 37 the 39 groups 38 glazed 39 groups conclusion : the silane ( monobond s )/adhesive ( heliobond )/variolink ii resin cement [combination] benefitted from glazing the zirconia surface , but the zirconia primer/multilink automix resin cement combination alone also provided sufficient bond strength to zirconia . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 23 but 0 ###LEFT-WALL### 39 . 1 conclusion 2 : 2 : 4 silane 3 the 4 silane 4 silane 8 )/adhesive 5 ( 8 )/adhesive 6 monobond 7 s 6 monobond 8 )/adhesive 8 )/adhesive 11 )/variolink 8 )/adhesive 22 , 9 ( 11 )/variolink 10 heliobond 11 )/variolink 11 )/variolink 12 ii 11 )/variolink 14 cement 11 )/variolink 16 benefitted 11 )/variolink 22 , 13 resin 14 cement 14 cement 16 benefitted 16 benefitted 17 from 17 from 18 glazing 18 glazing 21 surface 19 the 21 surface 20 zirconia 21 surface 23 but 30 combination 23 but 33 provided 24 the 30 combination 25 zirconia 26 primer/multilink 26 primer/multilink 30 combination 27 automix 28 resin 28 resin 30 combination 29 cement 30 combination 30 combination 33 provided 31 alone 33 provided 32 also 33 provided 33 provided 36 strength 33 provided 37 to 34 sufficient 35 bond 35 bond 36 strength 37 to 38 zirconia purpose : to compare the bond strengths of young and old dentin using a single - bottle [etch] - and [-] rinse adhesive system with two acid - etching times ( 15 s and 30 s ) , [and] to examine the correlation between dentin hardness and bond strength . 0 ###LEFT-WALL### 1 purpose 0 ###LEFT-WALL### 2 : 2 : 3 to 2 : 4 compare 3 to 4 compare 4 compare 7 strengths 4 compare 13 using 5 the 7 strengths 6 bond 7 strengths 7 strengths 8 of 8 of 12 dentin 9 young 10 and 10 and 11 old 10 and 12 dentin 13 using 24 system 13 using 25 with 14 a 15 single 14 a 17 bottle 15 single 16 - 15 single 17 bottle 17 bottle 20 and 19 - 20 and 20 and 22 rinse 20 and 23 adhesive 23 adhesive 24 system 25 with 30 times 26 two 30 times 27 acid 28 - 27 acid 29 etching 29 etching 30 times 30 times 34 and 30 times 40 to 31 ( 34 and 32 15 33 s 33 s 34 and 34 and 36 s 34 and 37 ) 35 30 36 s 38 , 40 to 40 to 41 examine 40 to 50 . 41 examine 43 correlation 42 the 43 correlation 43 correlation 44 between 44 between 47 and 45 dentin 46 hardness 46 hardness 47 and 47 and 49 strength 48 bond 49 strength materials and methods : twenty - four molars from 18 - to 22 - or 55 - to 60 - year [-] old patients were prepared to expose the occlusal dentin , cut into two equal parts , and assigned to four groups [(] g ) [,] varying [the] etching time ( 15 s and 30 s ) [and] dentin age ( young [ [y] ]or old [[] o ] ) [:] g15y , g30y , g15o and g30o . 0 ###LEFT-WALL### 3 methods 0 ###LEFT-WALL### 4 : 0 ###LEFT-WALL### 6 - 1 materials 3 methods 2 and 3 methods 3 methods 4 : 4 : 5 twenty 6 - 8 molars 6 - 15 or 7 four 8 molars 8 molars 9 from 8 molars 12 to 9 from 10 18 11 - 12 to 12 to 13 22 12 to 14 - 14 - 15 or 15 or 16 55 15 or 17 - 16 55 17 - 17 - 24 patients 18 to 19 60 18 to 20 - 18 to 24 patients 21 year 24 patients 23 old 24 patients 24 patients 25 were 25 were 26 prepared 26 prepared 27 to 27 to 32 , 28 expose 31 dentin 28 expose 32 , 29 the 31 dentin 30 occlusal 31 dentin 32 , 33 cut 32 , 34 into 32 , 39 and 34 into 35 two 36 equal 37 parts 37 parts 39 and 38 , 39 and 39 and 40 assigned 39 and 46 ) 39 and 48 varying 39 and 50 etching 40 assigned 41 to 41 to 43 groups 42 four 43 groups 43 groups 45 g 50 etching 51 time 50 etching 61 age 51 time 55 and 52 ( 55 and 53 15 54 s 54 s 55 and 55 and 57 s 55 and 58 ) 56 30 57 s 60 dentin 61 age 61 age 73 g15y 62 ( 73 g15y 63 young 67 old 63 young 71 ) 63 young 73 g15y 64 [ 67 old 66 ]or 67 old 67 old 69 o 67 old 70 ] 73 g15y 75 g30y 73 g15y 80 . 74 , 75 g30y 75 g30y 78 and 75 g30y 80 . 76 , 78 and 77 g15o 78 and 78 and 79 g30o 78 and 80 . after etching , adpersinglebond ( 3 m espe ) adhesive was applied and the tooth was built up with a composite ( filtek z250 ) . 0 ###LEFT-WALL### 10 adhesive 0 ###LEFT-WALL### 12 applied 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 26 . 1 after 2 etching 1 after 3 , 1 after 10 adhesive 4 adpersinglebond 8 espe 4 adpersinglebond 10 adhesive 5 ( 8 espe 6 3 7 m 7 m 8 espe 8 espe 9 ) 10 adhesive 11 was 11 was 12 applied 13 and 15 tooth 13 and 17 built 14 the 15 tooth 15 tooth 16 was 16 was 17 built 17 built 18 up 17 built 19 with 19 with 21 composite 20 a 21 composite 21 composite 24 z250 22 ( 24 z250 23 filtek 24 z250 24 z250 25 ) the specimens were prepared for the microtensile bond strength test ( μtbs ) at a crosshead speed of 0.5 mm/min and the interfaces were observed under sem . 0 ###LEFT-WALL### 2 specimens 0 ###LEFT-WALL### 3 were 0 ###LEFT-WALL### 21 and 0 ###LEFT-WALL### 28 . 1 the 2 specimens 2 specimens 3 were 3 were 4 prepared 4 prepared 5 for 4 prepared 14 at 5 for 10 test 6 the 10 test 7 microtensile 10 test 8 bond 10 test 9 strength 10 test 10 test 12 μtbs 11 ( 12 μtbs 12 μtbs 13 ) 14 at 17 speed 15 a 16 crosshead 15 a 17 speed 16 crosshead 17 speed 17 speed 18 of 18 of 20 mm/min 19 0.5 20 mm/min 21 and 23 interfaces 21 and 25 observed 22 the 23 interfaces 23 interfaces 24 were 24 were 25 observed 25 observed 26 under 26 under 27 sem also , the knoop [hardness] ( khn ) [of] young [vs] old dentin was measured . 0 ###LEFT-WALL### 13 dentin 0 ###LEFT-WALL### 14 was 0 ###LEFT-WALL### 16 . 1 also 2 , 1 also 13 dentin 3 the 13 dentin 4 knoop 7 khn 6 ( 7 khn 7 khn 8 ) 7 khn 13 dentin 10 young 12 old 12 old 13 dentin 13 dentin 14 was 14 was 15 measured results : the mean ( ± sd ) μtbs ( mpa ) were : g15y = 45.9 ( ± 10.7 )a , g15o = 34.1 ( ± 9.4 )b , g30y = 48.6 ( ± 14.3 )a and g30o [=] 47.7 ( ± 11.0 )a . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 9 μtbs 2 : 13 were 2 : 14 : 2 : 22 , 3 the 9 μtbs 4 mean 7 sd 4 mean 8 ) 4 mean 9 μtbs 5 ( 7 sd 6 ± 7 sd 7 sd 8 ) 9 μtbs 11 mpa 9 μtbs 13 were 10 ( 11 mpa 11 mpa 12 ) 14 : 15 g15y 14 : 16 = 15 g15y 16 = 16 = 17 45.9 17 45.9 19 ± 18 ( 19 ± 19 ± 20 10.7 19 ± 21 )a 19 ± 22 , 20 10.7 21 )a 22 , 23 g15o 22 , 24 = 22 , 30 , 23 g15o 24 = 24 = 25 34.1 25 34.1 27 ± 26 ( 27 ± 27 ± 28 9.4 27 ± 29 )b 27 ± 30 , 28 9.4 29 )b 30 , 31 g30y 30 , 32 = 31 g30y 32 = 32 = 33 48.6 33 48.6 38 and 34 ( 38 and 35 ± 37 )a 36 14.3 37 )a 37 )a 38 and 38 and 39 g30o 38 and 45 )a 38 and 46 . 39 g30o 41 47.7 42 ( 45 )a 43 ± 45 )a 44 11.0 45 )a 45 )a 46 . two - way anova showed no difference in μtbs between young and old dentin . 0 ###LEFT-WALL### 1 two 0 ###LEFT-WALL### 2 - 2 - 4 anova 2 - 5 showed 2 - 15 . 3 way 4 anova 4 anova 5 showed 5 showed 7 difference 5 showed 8 in 5 showed 10 between 6 no 7 difference 8 in 9 μtbs 10 between 14 dentin 11 young 12 and 12 and 13 old 12 and 14 dentin old dentin acid etched for 15 s ( g15o ) had a lower μtbs [than] when acid etched for 30 s ( g30o ) . 0 ###LEFT-WALL### 3 acid 0 ###LEFT-WALL### 11 had 0 ###LEFT-WALL### 25 . 1 old 3 acid 2 dentin 3 acid 3 acid 4 etched 3 acid 9 g15o 3 acid 11 had 4 etched 5 for 5 for 7 s 6 15 7 s 8 ( 9 g15o 9 g15o 10 ) 11 had 14 μtbs 12 a 14 μtbs 13 lower 14 μtbs 14 μtbs 16 when 14 μtbs 23 g30o 16 when 17 acid 16 when 18 etched 17 acid 18 etched 18 etched 19 for 19 for 21 s 20 30 21 s 22 ( 23 g30o 23 g30o 24 ) dentin [hardness] was higher for old dentin ( 67.0 ± 4.8khn ) than young dentin ( 63.7 ± 2.9khn ) ( p < 0.004 ) . 0 ###LEFT-WALL### 1 dentin 0 ###LEFT-WALL### 3 was 0 ###LEFT-WALL### 26 . 1 dentin 3 was 3 was 4 higher 4 higher 5 for 4 higher 13 than 5 for 7 dentin 6 old 7 dentin 7 dentin 11 4.8khn 8 ( 11 4.8khn 9 67.0 11 4.8khn 10 ± 11 4.8khn 11 4.8khn 12 ) 13 than 15 dentin 14 young 15 dentin 15 dentin 19 2.9khn 15 dentin 23 < 16 ( 19 2.9khn 17 63.7 19 2.9khn 18 ± 19 2.9khn 19 2.9khn 20 ) 21 ( 23 < 22 p 23 < 23 < 24 0.004 23 < 25 ) no correlation between μtbs and dentin hardness was observed . 0 ###LEFT-WALL### 2 correlation 0 ###LEFT-WALL### 9 observed 0 ###LEFT-WALL### 10 . 1 no 2 correlation 2 correlation 3 between 2 correlation 8 was 3 between 5 and 4 μtbs 5 and 5 and 7 hardness 6 dentin 7 hardness 8 was 9 observed resin tags were larger and more numerous for young dentin . 0 ###LEFT-WALL### 2 tags 0 ###LEFT-WALL### 3 were 0 ###LEFT-WALL### 11 . 1 resin 2 tags 2 tags 3 were 3 were 5 and 3 were 7 numerous 4 larger 5 and 5 and 6 more 7 numerous 8 for 8 for 10 dentin 9 young 10 dentin the hybrid layer formed in intertubular old dentin ( g15o ) was very thin . 0 ###LEFT-WALL### 3 layer 0 ###LEFT-WALL### 12 was 0 ###LEFT-WALL### 15 . 1 the 3 layer 2 hybrid 3 layer 3 layer 4 formed 3 layer 12 was 4 formed 5 in 5 in 8 dentin 6 intertubular 8 dentin 7 old 8 dentin 8 dentin 10 g15o 9 ( 10 g15o 10 g15o 11 ) 12 was 14 thin 13 very 14 thin conclusion : bonding to old dentin with 30 s of etching time resulted in higher bond strength and more homogeneous hybrid layer formation than dentin acid etched for 15 s . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 22 layer 0 ###LEFT-WALL### 31 . 2 : 3 bonding 2 : 13 resulted 3 bonding 4 to 3 bonding 13 resulted 4 to 6 dentin 5 old 6 dentin 6 dentin 7 with 6 dentin 10 of 7 with 9 s 8 30 9 s 10 of 11 etching 11 etching 12 time 13 resulted 14 in 14 in 16 bond 15 higher 16 bond 16 bond 18 and 16 bond 22 layer 17 strength 18 and 18 and 21 hybrid 18 and 22 layer 19 more 20 homogeneous 20 homogeneous 21 hybrid 22 layer 23 formation 22 layer 24 than 24 than 26 acid 24 than 28 for 25 dentin 26 acid 26 acid 27 etched 28 for 30 s 29 15 30 s purpose : to evaluate the effect of chlorhexidine on the presence of collagen in aged resin - dentin bonds produced on sound and caries - affected dentin . 0 ###LEFT-WALL### 1 purpose 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 28 . 2 : 3 to 2 : 4 evaluate 3 to 4 evaluate 4 evaluate 6 effect 4 evaluate 26 affected 5 the 6 effect 6 effect 7 of 6 effect 9 on 6 effect 19 bonds 6 effect 26 affected 7 of 8 chlorhexidine 9 on 11 presence 10 the 11 presence 11 presence 12 of 12 of 13 collagen 13 collagen 14 in 14 in 16 resin 15 aged 16 resin 17 - 19 bonds 18 dentin 19 bonds 19 bonds 20 produced 19 bonds 25 - 20 produced 21 on 21 on 23 and 22 sound 23 and 23 and 24 caries 26 affected 27 dentin materials and methods : flat dentin surfaces were obtained from 16 sound molars , from which 8 were microbiologically processed for induction of caries . 0 ###LEFT-WALL### 3 methods 0 ###LEFT-WALL### 4 : 1 materials 2 and 2 and 3 methods 4 : 7 surfaces 4 : 9 obtained 5 flat 7 surfaces 6 dentin 7 surfaces 7 surfaces 8 were 8 were 9 obtained 9 obtained 10 from 10 from 13 molars 11 16 13 molars 12 sound 13 molars 13 molars 15 from 14 , 15 from 15 from 16 which 15 from 17 8 15 from 20 processed 15 from 25 . 17 8 18 were 18 were 20 processed 19 microbiologically 20 processed 20 processed 21 for 21 for 22 induction 22 induction 23 of 23 of 24 caries single bond 2 was applied to both sound and caries - affected substrates . 0 ###LEFT-WALL### 2 bond 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 11 - 1 single 2 bond 2 bond 3 2 2 bond 9 and 4 was 5 applied 4 was 9 and 5 applied 6 to 6 to 8 sound 7 both 8 sound 9 and 10 caries 11 - 13 substrates 11 - 14 . 12 affected 13 substrates in half of the teeth assigned for 6 - month storage in water , the phosphoric acid demineralized dentin was impregnated with 2 % chlorhexidine before the application of the adhesive . 0 ###LEFT-WALL### 19 dentin 0 ###LEFT-WALL### 21 impregnated 0 ###LEFT-WALL### 32 . 1 in 2 half 1 in 14 , 1 in 19 dentin 2 half 3 of 3 of 5 teeth 4 the 5 teeth 5 teeth 6 assigned 5 teeth 7 for 7 for 8 6 8 6 11 storage 9 - 11 storage 10 month 11 storage 11 storage 12 in 11 storage 14 , 12 in 13 water 15 the 19 dentin 16 phosphoric 19 dentin 17 acid 18 demineralized 18 demineralized 19 dentin 19 dentin 20 was 20 was 21 impregnated 21 impregnated 22 with 21 impregnated 26 before 22 with 25 chlorhexidine 23 2 24 % 24 % 25 chlorhexidine 26 before 28 application 27 the 28 application 28 application 29 of 29 of 31 adhesive 30 the 31 adhesive specimens ( 2 x 2 x 5 mm ) were produced and stored in water for 24 h , or 6 months in either water or mineral oil . 0 ###LEFT-WALL### 1 specimens 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 29 . 1 specimens 4 x 1 specimens 12 and 2 ( 4 x 3 2 4 x 4 x 6 x 4 x 9 ) 5 2 6 x 6 x 8 mm 7 5 8 mm 10 were 11 produced 10 were 12 and 12 and 13 stored 12 and 14 in 12 and 23 in 14 in 20 or 15 water 16 for 15 water 20 or 16 for 18 h 17 24 18 h 19 , 20 or 20 or 22 months 21 6 22 months 23 in 26 or 24 either 26 or 25 water 26 or 26 or 28 oil 27 mineral 28 oil the specimens were subjected to histological processing and sections were stained with goldner 's trichrome . 0 ###LEFT-WALL### 2 specimens 0 ###LEFT-WALL### 11 stained 0 ###LEFT-WALL### 16 . 1 the 2 specimens 2 specimens 8 and 2 specimens 10 were 3 were 4 subjected 3 were 8 and 4 subjected 5 to 5 to 7 processing 6 histological 7 processing 8 and 9 sections 10 were 11 stained 11 stained 12 with 12 with 15 trichrome 13 goldner 14 's 14 's 15 trichrome the thickness of the zone of exposed collagen was measured by optical microscopy and the data were subjected to two - way anova and tukey 's test ( α [=] 0.05 ) . 0 ###LEFT-WALL### 2 thickness 0 ###LEFT-WALL### 9 was 0 ###LEFT-WALL### 14 and 0 ###LEFT-WALL### 33 . 1 the 2 thickness 2 thickness 3 of 2 thickness 9 was 3 of 5 zone 4 the 5 zone 5 zone 6 of 6 of 8 collagen 7 exposed 8 collagen 9 was 10 measured 10 measured 11 by 11 by 13 microscopy 12 optical 13 microscopy 14 and 16 data 14 and 18 subjected 15 the 16 data 16 data 17 were 17 were 18 subjected 18 subjected 19 to 19 to 20 two 20 two 24 and 21 - 24 and 22 way 23 anova 23 anova 24 and 24 and 27 test 24 and 29 α 24 and 32 ) 25 tukey 26 's 26 's 27 test 28 ( 29 α 29 α 31 0.05 29 α 32 ) results : there was no statistically significant difference ( p > 0.05 ) between sound and caries - affected dentin regardless of the storage condition . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 3 there 2 : 4 was 2 : 26 . 3 there 4 was 4 was 8 difference 4 was 14 between 4 was 22 of 5 no 8 difference 6 statistically 7 significant 7 significant 8 difference 8 difference 11 > 9 ( 11 > 10 p 11 > 11 > 12 0.05 11 > 13 ) 14 between 20 dentin 15 sound 16 and 16 and 17 caries 16 and 18 - 16 and 19 affected 16 and 20 dentin 21 regardless 22 of 22 of 25 condition 23 the 25 condition 24 storage 25 condition for both substrates , significantly greater collagen exposure was observed after 6 months in water . 0 ###LEFT-WALL### 8 exposure 0 ###LEFT-WALL### 10 observed 0 ###LEFT-WALL### 16 . 1 for 3 substrates 1 for 4 , 1 for 8 exposure 2 both 3 substrates 5 significantly 6 greater 6 greater 8 exposure 7 collagen 8 exposure 8 exposure 9 was 9 was 10 observed 10 observed 11 after 10 observed 14 in 11 after 13 months 12 6 13 months 14 in 15 water chlorhexidine - treated groups resulted in similar collagen exposure to that of the control and 6 months in water groups ( p > 0.05 ) , while no increase of the exposed collagen zone was observed after mineral oil storage . 0 ###LEFT-WALL### 4 groups 0 ###LEFT-WALL### 5 resulted 1 chlorhexidine 2 - 1 chlorhexidine 4 groups 3 treated 4 groups 4 groups 5 resulted 5 resulted 6 in 5 resulted 10 to 5 resulted 18 in 5 resulted 27 while 6 in 9 exposure 7 similar 9 exposure 8 collagen 9 exposure 10 to 15 and 11 that 12 of 11 that 15 and 12 of 14 control 13 the 14 control 15 and 17 months 16 6 17 months 18 in 20 groups 19 water 20 groups 20 groups 23 > 21 ( 23 > 22 p 23 > 23 > 24 0.05 23 > 25 ) 26 , 27 while 27 while 29 increase 27 while 36 observed 27 while 41 . 28 no 29 increase 29 increase 30 of 29 increase 35 was 30 of 34 zone 31 the 34 zone 32 exposed 34 zone 33 collagen 34 zone 35 was 36 observed 36 observed 37 after 37 after 40 storage 38 mineral 39 oil 39 oil 40 storage conclusion : aging in water resulted in degradation of the resin - dentin bond , as demonstrated by the increase of the zone of exposed collagen . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 3 aging 2 : 6 resulted 2 : 27 . 3 aging 4 in 3 aging 6 resulted 4 in 5 water 6 resulted 7 in 6 resulted 18 by 7 in 8 degradation 8 degradation 9 of 9 of 11 resin 10 the 11 resin 11 resin 14 bond 11 resin 17 demonstrated 12 - 14 bond 13 dentin 14 bond 14 bond 15 , 15 , 17 demonstrated 16 as 17 demonstrated 18 by 20 increase 19 the 20 increase 20 increase 21 of 21 of 23 zone 22 the 23 zone 23 zone 24 of 24 of 26 collagen 25 exposed 26 collagen however , the degradation of the exposed collagen was decelerated in the presence of chlorhexidine . 0 ###LEFT-WALL### 4 degradation 0 ###LEFT-WALL### 10 decelerated 0 ###LEFT-WALL### 16 . 1 however 2 , 1 however 4 degradation 3 the 4 degradation 4 degradation 5 of 4 degradation 9 was 5 of 8 collagen 6 the 8 collagen 7 exposed 8 collagen 9 was 10 decelerated 10 decelerated 11 in 11 in 13 presence 12 the 13 presence 13 presence 14 of 14 of 15 chlorhexidine objective : to study the effectiveness of simply [-] performed balancing exercises in fall prevention . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 16 . 2 : 3 to 2 : 4 study 3 to 4 study 4 study 6 effectiveness 4 study 13 in 5 the 6 effectiveness 6 effectiveness 7 of 7 of 12 exercises 8 simply 10 performed 10 performed 12 exercises 11 balancing 12 exercises 13 in 15 prevention 14 fall 15 prevention design : pre - and post - trial . 0 ###LEFT-WALL### 1 design 0 ###LEFT-WALL### 2 : 2 : 5 and 2 : 7 - 3 pre 5 and 4 - 5 and 5 and 6 post 7 - 8 trial 7 - 9 . setting : university [hospital] from january 2009 to may 2010 . 0 ###LEFT-WALL### 1 setting 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 11 . 1 setting 2 : 2 : 3 university 3 university 5 from 3 university 8 to 5 from 6 january 6 january 7 2009 8 to 9 may 9 may 10 2010 participants : elderly [with] falls in the previous year . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 2 : 2 : 3 elderly 2 : 5 falls 2 : 10 . 3 elderly 5 falls 5 falls 6 in 6 in 9 year 7 the 9 year 8 previous 9 year intervention : simple balancing exercise was performed at home every day and was recorded in the booklet . 0 ###LEFT-WALL### 1 intervention 0 ###LEFT-WALL### 2 : 2 : 3 simple 2 : 12 and 2 : 18 . 3 simple 4 balancing 3 simple 6 was 4 balancing 5 exercise 6 was 12 and 7 performed 8 at 7 performed 11 day 7 performed 12 and 8 at 9 home 10 every 11 day 12 and 13 was 12 and 15 in 13 was 14 recorded 15 in 17 booklet 16 the 17 booklet measurements : new falling events and a battery of balancing abilities including the timed up and go test ( tugt ) , chair stand , functional reach , and berg balance scale - short form were evaluated at baseline , 3 - , 6 - , 9 - , [and] 12 - month periods . 0 ###LEFT-WALL### 1 measurements 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 33 - 0 ###LEFT-WALL### 55 . 1 measurements 2 : 2 : 16 and 3 new 4 falling 4 falling 5 events 5 events 6 and 6 and 8 battery 6 and 9 of 6 and 12 including 6 and 16 and 7 a 8 battery 9 of 10 balancing 10 balancing 11 abilities 12 including 15 up 13 the 15 up 14 timed 15 up 16 and 32 scale 16 and 33 - 17 go 18 test 18 test 20 tugt 19 ( 20 tugt 20 tugt 21 ) 20 tugt 22 , 22 , 24 stand 22 , 25 , 23 chair 24 stand 25 , 27 reach 25 , 29 and 26 functional 27 reach 28 , 29 and 29 and 31 balance 29 and 32 scale 30 berg 31 balance 33 - 35 form 33 - 37 evaluated 33 - 49 , 34 short 35 form 35 form 36 were 36 were 37 evaluated 37 evaluated 38 at 38 at 39 baseline 39 baseline 41 3 39 baseline 44 6 39 baseline 47 9 40 , 41 3 41 3 42 - 43 , 44 6 44 6 45 - 46 , 47 9 47 9 48 - 49 , 51 12 49 , 52 - 52 - 54 periods 53 month 54 periods fear of falling and quality of life scores were assessed at baseline and 12 [-] month periods . 0 ###LEFT-WALL### 8 scores 0 ###LEFT-WALL### 10 assessed 0 ###LEFT-WALL### 18 . 1 fear 2 of 1 fear 4 and 2 of 3 falling 4 and 5 quality 4 and 6 of 4 and 8 scores 6 of 7 life 8 scores 9 were 9 were 10 assessed 10 assessed 11 at 11 at 13 and 12 baseline 13 and 13 and 17 periods 14 12 16 month 16 month 17 periods results : 146 subjects were recruited , [116] female ( 79.5 % ) with a mean age of 67.1 years . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 21 . 1 results 2 : 2 : 3 146 2 : 14 with 3 146 4 subjects 3 146 5 were 3 146 6 recruited 3 146 12 % 4 subjects 5 were 6 recruited 7 , 6 recruited 9 female 10 ( 12 % 11 79.5 12 % 12 % 13 ) 14 with 17 age 15 a 17 age 16 mean 17 age 17 age 18 of 18 of 20 years 19 67.1 20 years at the end of the study , 49 % of participants had not fallen . 0 ###LEFT-WALL### 9 % 0 ###LEFT-WALL### 14 fallen 0 ###LEFT-WALL### 15 . 1 at 3 end 1 at 7 , 1 at 9 % 2 the 3 end 3 end 4 of 4 of 6 study 5 the 6 study 8 49 9 % 9 % 10 of 9 % 12 had 10 of 11 participants 12 had 13 not 12 had 14 fallen all of the balancing abilities were compared between frequent and infrequent fallers and were significantly improved ( p<0.001 ) except for functional reach in the frequent fall group . 0 ###LEFT-WALL### 1 all 0 ###LEFT-WALL### 7 compared 0 ###LEFT-WALL### 29 . 1 all 2 of 1 all 6 were 2 of 5 abilities 3 the 5 abilities 4 balancing 5 abilities 6 were 7 compared 7 compared 8 between 7 compared 20 except 7 compared 24 in 8 between 10 and 9 frequent 10 and 10 and 11 infrequent 10 and 13 and 10 and 18 p<0.001 12 fallers 13 and 13 and 14 were 14 were 16 improved 15 significantly 16 improved 17 ( 18 p<0.001 18 p<0.001 19 ) 20 except 21 for 21 for 23 reach 22 functional 23 reach 24 in 28 group 25 the 28 group 26 frequent 27 fall 27 fall 28 group most subjects ( 72 % - 79 % ) complied well with the exercise program . 0 ###LEFT-WALL### 2 subjects 0 ###LEFT-WALL### 10 complied 0 ###LEFT-WALL### 16 . 1 most 2 subjects 2 subjects 5 % 2 subjects 10 complied 3 ( 5 % 4 72 5 % 5 % 8 % 5 % 9 ) 6 - 8 % 7 79 8 % 8 % 9 ) 10 complied 11 well 10 complied 12 with 12 with 15 program 13 the 15 program 14 exercise 15 program however , compliance had no effect on balancing abilities . 0 ###LEFT-WALL### 3 compliance 0 ###LEFT-WALL### 4 had 0 ###LEFT-WALL### 10 . 1 however 2 , 1 however 3 compliance 3 compliance 4 had 4 had 6 effect 4 had 7 on 5 no 6 effect 7 on 8 balancing 8 balancing 9 abilities about 36.4 % of participants had adverse events from exercise , of which knee pain was the top ranked . 0 ###LEFT-WALL### 3 % 0 ###LEFT-WALL### 6 had 0 ###LEFT-WALL### 11 , 0 ###LEFT-WALL### 20 . 1 about 2 36.4 2 36.4 3 % 3 % 4 of 3 % 6 had 4 of 5 participants 6 had 8 events 7 adverse 8 events 8 events 9 from 9 from 10 exercise 11 , 12 of 11 , 19 ranked 12 of 13 which 12 of 15 pain 12 of 16 was 13 which 15 pain 14 knee 15 pain 16 was 18 top 16 was 19 ranked 17 the 18 top the quality of life and the fall efficacy scores increased significantly at the end of the study . 0 ###LEFT-WALL### 5 and 0 ###LEFT-WALL### 18 . 1 the 2 quality 2 quality 3 of 2 quality 5 and 3 of 4 life 5 and 9 scores 5 and 10 increased 6 the 9 scores 7 fall 9 scores 8 efficacy 9 scores 10 increased 11 significantly 10 increased 12 at 12 at 14 end 13 the 14 end 14 end 15 of 15 of 17 study 16 the 17 study factors affecting falling were compliance with exercise [(] adjusted odds ratio [ or ] : 2.55 [,] 95 % confidence [intervals] [ ci ] : 1.04 [,] 6.30 [ )( [a] history [of] falling ≥3 times in the previous year ( adjusted or : 3.76 , 95 % ci [:] 1.18 , 11.98 ) . 0 ###LEFT-WALL### 1 factors 0 ###LEFT-WALL### 4 were 1 factors 2 affecting 1 factors 4 were 2 affecting 3 falling 4 were 5 compliance 4 were 6 with 6 with 10 odds 6 with 16 2.55 7 exercise 9 adjusted 9 adjusted 10 odds 10 odds 11 ratio 10 odds 15 : 11 ratio 13 or 11 ratio 15 : 12 [ 13 or 13 or 14 ] 16 2.55 20 confidence 16 2.55 25 : 18 95 19 % 19 % 20 confidence 20 confidence 23 ci 20 confidence 25 : 22 [ 23 ci 23 ci 24 ] 25 : 36 times 26 1.04 32 history 28 6.30 32 history 32 history 36 times 34 falling 35 ≥3 35 ≥3 36 times 36 times 37 in 36 times 43 or 36 times 44 : 37 in 40 year 38 the 39 previous 38 the 40 year 40 year 42 adjusted 41 ( 42 adjusted 43 or 44 : 44 : 45 3.76 45 3.76 49 ci 46 , 49 ci 47 95 49 ci 48 % 49 ci 49 ci 51 1.18 49 ci 53 11.98 49 ci 55 . 52 , 53 11.98 53 11.98 54 ) conclusion : performing simply - designed balancing exercises , at least 3 days per week , can increase balancing abilities , and decrease fall rates in the elderly with a history of [previous] falls . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 7 balancing 2 : 34 falls 2 : 35 . 3 performing 4 simply 3 performing 5 - 3 performing 7 balancing 6 designed 7 balancing 7 balancing 8 exercises 7 balancing 22 and 7 balancing 34 falls 8 exercises 13 days 8 exercises 22 and 9 , 11 least 9 , 13 days 10 at 11 least 12 3 13 days 13 days 14 per 13 days 16 , 14 per 15 week 17 can 18 increase 17 can 22 and 18 increase 20 abilities 19 balancing 20 abilities 21 , 22 and 22 and 23 decrease 22 and 26 in 22 and 29 with 22 and 32 of 23 decrease 25 rates 24 fall 25 rates 26 in 28 elderly 27 the 28 elderly 29 with 31 history 30 a 31 history 31 history 32 of however , strategies to [encourage] elderly compliance may prevent falling . 0 ###LEFT-WALL### 3 strategies 0 ###LEFT-WALL### 9 prevent 0 ###LEFT-WALL### 11 . 1 however 2 , 1 however 3 strategies 3 strategies 4 to 3 strategies 8 may 4 to 7 compliance 6 elderly 7 compliance 8 may 9 prevent 9 prevent 10 falling taken once a year , intravenous zoledronic acid ( zol ) ( reclast® or aclasta® ) is a third - generation nitrogen - containing bisphosphonate that is effective compared with placebo [in] reducing the risk of fractures in patients with postmenopausal osteoporosis and recent low - trauma hip fracture . 0 ###LEFT-WALL### 24 containing 0 ###LEFT-WALL### 29 compared 0 ###LEFT-WALL### 50 . 1 taken 2 once 1 taken 23 - 1 taken 24 containing 2 once 4 year 2 once 17 is 3 a 4 year 4 year 8 acid 4 year 17 is 5 , 8 acid 6 intravenous 8 acid 7 zoledronic 8 acid 8 acid 10 zol 8 acid 14 or 8 acid 16 ) 9 ( 10 zol 10 zol 11 ) 12 ( 14 or 13 reclast® 14 or 14 or 15 aclasta® 14 or 16 ) 17 is 19 third 18 a 19 third 19 third 22 nitrogen 20 - 22 nitrogen 21 generation 22 nitrogen 22 nitrogen 23 - 24 containing 25 bisphosphonate 24 containing 29 compared 25 bisphosphonate 26 that 25 bisphosphonate 27 is 26 that 27 is 27 is 28 effective 29 compared 30 with 29 compared 35 risk 29 compared 40 with 30 with 33 reducing 31 placebo 33 reducing 34 the 35 risk 35 risk 36 of 36 of 37 fractures 37 fractures 38 in 38 in 39 patients 40 with 43 and 41 postmenopausal 42 osteoporosis 42 osteoporosis 43 and 43 and 49 fracture 44 recent 47 trauma 45 low 46 - 45 low 47 trauma 47 trauma 49 fracture 48 hip 49 fracture in glucocorticoid - induced osteoporosis , there is no significant difference between zol and risedronate for new fractures . 0 ###LEFT-WALL### 7 there 0 ###LEFT-WALL### 8 is 0 ###LEFT-WALL### 19 . 1 in 2 glucocorticoid 1 in 7 there 2 glucocorticoid 5 osteoporosis 3 - 5 osteoporosis 4 induced 5 osteoporosis 5 osteoporosis 6 , 7 there 8 is 8 is 11 difference 9 no 11 difference 10 significant 11 difference 11 difference 12 between 11 difference 16 for 12 between 14 and 13 zol 14 and 14 and 15 risedronate 16 for 18 fractures 17 new 18 fractures improvements in bone mineral density and early reduction of bone remodeling markers are observed in postmenopausal osteoporosis , recent low - trauma hip fracture , and glucocorticoid - induced osteoporosis . 0 ###LEFT-WALL### 6 and 0 ###LEFT-WALL### 14 observed 0 ###LEFT-WALL### 31 . 1 improvements 2 in 1 improvements 6 and 2 in 5 density 3 bone 5 density 4 mineral 5 density 6 and 8 reduction 6 and 9 of 6 and 13 are 7 early 8 reduction 9 of 12 markers 10 bone 12 markers 11 remodeling 12 markers 13 are 14 observed 14 observed 15 in 15 in 26 and 16 postmenopausal 17 osteoporosis 17 osteoporosis 18 , 18 , 24 fracture 18 , 26 and 19 recent 22 trauma 20 low 21 - 20 low 22 trauma 22 trauma 23 hip 23 hip 24 fracture 25 , 26 and 26 and 30 osteoporosis 27 glucocorticoid 28 - 27 glucocorticoid 30 osteoporosis 29 induced 30 osteoporosis given that zol is generally well tolerated and very convenient , it is an interesting therapeutic option for aging patients who take multiple oral drugs , who have adherence [or] gastrointestinal tolerance issues , and who have an indication for oral bisphosphonates . 0 ###LEFT-WALL### 1 given 0 ###LEFT-WALL### 4 is 0 ###LEFT-WALL### 8 and 1 given 2 that 1 given 4 is 3 zol 4 is 4 is 7 tolerated 5 generally 7 tolerated 6 well 7 tolerated 8 and 12 it 8 and 13 is 9 very 10 convenient 10 convenient 11 , 10 convenient 12 it 12 it 13 is 13 is 17 option 14 an 15 interesting 14 an 17 option 15 interesting 17 option 16 therapeutic 17 option 17 option 18 for 18 for 19 aging 19 aging 20 patients 20 patients 21 who 20 patients 22 take 21 who 22 take 22 take 25 drugs 23 multiple 24 oral 24 oral 25 drugs 25 drugs 27 who 26 , 27 who 27 who 28 have 27 who 43 . 28 have 35 and 28 have 37 have 29 adherence 33 issues 31 gastrointestinal 32 tolerance 32 tolerance 33 issues 33 issues 35 and 34 , 35 and 35 and 36 who 37 have 39 indication 37 have 40 for 38 an 39 indication 40 for 42 bisphosphonates 41 oral 42 bisphosphonates zol is not recommended for patients with severe renal impairment . 0 ###LEFT-WALL### 1 zol 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 11 . 1 zol 2 is 2 is 3 not 2 is 5 for 2 is 7 with 3 not 4 recommended 5 for 6 patients 7 with 10 impairment 8 severe 10 impairment 9 renal 10 impairment vitamin d deficiency should be corrected before the administration of zol . 0 ###LEFT-WALL### 3 deficiency 0 ###LEFT-WALL### 6 corrected 0 ###LEFT-WALL### 12 . 1 vitamin 2 d 1 vitamin 3 deficiency 3 deficiency 4 should 4 should 5 be 5 be 6 corrected 6 corrected 7 before 7 before 9 administration 8 the 9 administration 9 administration 10 of 10 of 11 zol diverse effects of memory training were observed in the literature . 0 ###LEFT-WALL### 2 effects 0 ###LEFT-WALL### 7 observed 0 ###LEFT-WALL### 11 . 1 diverse 2 effects 2 effects 3 of 2 effects 6 were 3 of 5 training 4 memory 5 training 6 were 7 observed 7 observed 8 in 8 in 10 literature 9 the 10 literature one possible factor is the amount of concurrent cognitive training received during the training program . 0 ###LEFT-WALL### 3 factor 0 ###LEFT-WALL### 4 is 0 ###LEFT-WALL### 16 . 1 one 3 factor 2 possible 3 factor 3 factor 4 is 4 is 6 amount 5 the 6 amount 6 amount 7 of 7 of 10 training 8 concurrent 10 training 9 cognitive 10 training 10 training 11 received 11 received 12 during 12 during 15 program 13 the 15 program 14 training 15 program in this pilot study , we recruited 24 elderly adults with [or] [without] concurrent cognitive stimulations to attend a memory - training program . 0 ###LEFT-WALL### 6 we 0 ###LEFT-WALL### 7 recruited 0 ###LEFT-WALL### 21 - 1 in 4 study 1 in 5 , 1 in 6 we 2 this 4 study 3 pilot 4 study 6 we 7 recruited 7 recruited 10 adults 7 recruited 11 with 7 recruited 17 to 8 24 10 adults 9 elderly 10 adults 11 with 16 stimulations 14 concurrent 16 stimulations 15 cognitive 16 stimulations 17 to 18 attend 18 attend 20 memory 19 a 20 memory 21 - 23 program 21 - 24 . 22 training 23 program findings suggested that elderly people without concurrent cognitive stimulation could benefit from a memory [-] training program in the form of improved initiation and memory functioning . 0 ###LEFT-WALL### 1 findings 0 ###LEFT-WALL### 11 benefit 0 ###LEFT-WALL### 27 . 1 findings 2 suggested 1 findings 3 that 1 findings 11 benefit 3 that 5 people 3 that 10 could 4 elderly 5 people 5 people 6 without 5 people 10 could 6 without 9 stimulation 7 concurrent 9 stimulation 8 cognitive 9 stimulation 11 benefit 12 from 11 benefit 18 in 12 from 17 program 13 a 14 memory 13 a 17 program 14 memory 17 program 16 training 17 program 18 in 20 form 19 the 20 form 20 form 21 of 21 of 24 and 22 improved 23 initiation 23 initiation 24 and 24 and 25 memory 24 and 26 functioning self - rated quality of life [measure] also showed improvements alongside the cognitive benefits . 0 ###LEFT-WALL### 4 quality 0 ###LEFT-WALL### 9 showed 0 ###LEFT-WALL### 15 . 1 self 2 - 1 self 4 quality 3 rated 4 quality 4 quality 5 of 4 quality 9 showed 5 of 6 life 8 also 9 showed 9 showed 10 improvements 9 showed 11 alongside 11 alongside 14 benefits 12 the 14 benefits 13 cognitive 14 benefits elderly people with regular concurrent cognitive stimulation , on the other hand , seemed to plateau [in] their level of performance and did not show any significant change . 0 ###LEFT-WALL### 2 people 0 ###LEFT-WALL### 22 and 0 ###LEFT-WALL### 29 . 1 elderly 2 people 2 people 3 with 2 people 22 and 3 with 7 stimulation 4 regular 7 stimulation 5 concurrent 7 stimulation 6 cognitive 7 stimulation 7 stimulation 9 on 8 , 9 on 9 on 12 hand 9 on 13 , 10 the 11 other 11 other 12 hand 14 seemed 15 to 14 seemed 16 plateau 14 seemed 22 and 15 to 16 plateau 16 plateau 19 level 18 their 19 level 19 level 20 of 20 of 21 performance 22 and 23 did 23 did 24 not 23 did 25 show 25 show 26 any 25 show 28 change 27 significant 28 change our preliminary findings suggested nonlinear concurrent cognitive stimulation in the elderly . 0 ###LEFT-WALL### 3 findings 0 ###LEFT-WALL### 4 suggested 0 ###LEFT-WALL### 12 . 1 our 3 findings 2 preliminary 3 findings 3 findings 4 suggested 4 suggested 8 stimulation 4 suggested 9 in 5 nonlinear 8 stimulation 6 concurrent 8 stimulation 7 cognitive 8 stimulation 9 in 11 elderly 10 the 11 elderly public interest alberta 's seniors task force members are deeply concerned about the privatization of long - term care in alberta that began during the klein era . 0 ###LEFT-WALL### 8 members 0 ###LEFT-WALL### 9 are 0 ###LEFT-WALL### 28 . 1 public 2 interest 2 interest 3 alberta 3 alberta 4 's 4 's 8 members 5 seniors 6 task 6 task 8 members 7 force 8 members 8 members 9 are 9 are 10 deeply 9 are 11 concerned 11 concerned 12 about 11 concerned 24 during 12 about 14 privatization 13 the 14 privatization 14 privatization 15 of 15 of 19 care 16 long 17 - 16 long 19 care 18 term 19 care 19 care 20 in 20 in 21 alberta 21 alberta 22 that 21 alberta 23 began 22 that 23 began 24 during 27 era 25 the 27 era 26 klein 27 era the move [away] from publicly funded and publicly administered long - term care is accelerating under the leadership of premier ed stelmach . 0 ###LEFT-WALL### 2 move 0 ###LEFT-WALL### 14 is 0 ###LEFT-WALL### 23 . 1 the 2 move 2 move 4 from 2 move 14 is 4 from 7 and 5 publicly 6 funded 6 funded 7 and 7 and 9 administered 7 and 13 care 8 publicly 9 administered 10 long 11 - 10 long 12 term 12 term 13 care 14 is 15 accelerating 15 accelerating 16 under 16 under 18 leadership 17 the 18 leadership 18 leadership 19 of 19 of 22 stelmach 20 premier 21 ed 21 ed 22 stelmach in making this shift [,] government will harvest short - term gain that can only result in long - term pain for people in need of such services . 0 ###LEFT-WALL### 13 that 0 ###LEFT-WALL### 16 result 0 ###LEFT-WALL### 29 . 1 in 2 making 1 in 13 that 2 making 12 gain 3 this 12 gain 4 shift 6 government 6 government 8 harvest 7 will 8 harvest 8 harvest 12 gain 9 short 10 - 9 short 11 term 11 term 12 gain 13 that 14 can 14 can 16 result 15 only 16 result 16 result 17 in 16 result 22 for 16 result 24 in 17 in 21 pain 18 long 19 - 18 long 20 term 20 term 21 pain 22 for 23 people 24 in 25 need 25 need 26 of 26 of 28 services 27 such 28 services long - term care ( ltc ) is but one piece of a [continuum] [of] care that stretches from living at home completely independently to the 24 - hour supervision and care provided in ltc facilities . 0 ###LEFT-WALL### 1 long 0 ###LEFT-WALL### 2 - 2 - 4 care 2 - 8 is 2 - 28 - 3 term 4 care 4 care 6 ltc 4 care 8 is 5 ( 6 ltc 6 ltc 7 ) 8 is 9 but 9 but 11 piece 10 one 11 piece 11 piece 12 of 11 piece 17 that 11 piece 18 stretches 12 of 16 care 13 a 16 care 17 that 18 stretches 18 stretches 19 from 18 stretches 24 independently 18 stretches 25 to 19 from 20 living 20 living 21 at 20 living 23 completely 21 at 22 home 25 to 27 24 26 the 27 24 28 - 31 and 28 - 33 provided 28 - 37 . 29 hour 30 supervision 30 supervision 31 and 31 and 32 care 31 and 33 provided 33 provided 34 in 34 in 36 facilities 35 ltc 36 facilities people want to stay at home as long as possible and to retain as much independence as they can , and they are often aided in doing so with informal care provided by family and friends . 0 ###LEFT-WALL### 1 people 0 ###LEFT-WALL### 2 want 0 ###LEFT-WALL### 21 and 0 ###LEFT-WALL### 32 provided 0 ###LEFT-WALL### 37 . 1 people 2 want 2 want 3 to 2 want 20 , 3 to 11 and 4 stay 5 at 4 stay 7 as 4 stay 10 possible 4 stay 11 and 5 at 6 home 7 as 8 long 9 as 10 possible 11 and 12 to 11 and 13 retain 12 to 13 retain 13 retain 16 independence 13 retain 17 as 14 as 15 much 15 much 16 independence 17 as 19 can 18 they 19 can 21 and 22 they 21 and 25 aided 22 they 23 are 23 are 24 often 23 are 25 aided 25 aided 26 in 26 in 27 doing 27 doing 28 so 27 doing 29 with 29 with 31 care 29 with 32 provided 30 informal 31 care 32 provided 33 by 33 by 35 and 34 family 35 and 35 and 36 friends these realities should inform the debates around the construction of the [continuum] [of] care . 0 ###LEFT-WALL### 2 realities 0 ###LEFT-WALL### 4 inform 0 ###LEFT-WALL### 15 . 1 these 2 realities 2 realities 3 should 3 should 4 inform 4 inform 6 debates 4 inform 7 around 5 the 6 debates 7 around 9 construction 8 the 9 construction 9 construction 10 of 10 of 14 care 11 the 14 care canada 's spending on facility - based long - term care puts us in the middle of the pack among oecd countries ; if we consider the whole of continuing care , combining ltc , supportive housing/assisted living and home - based healthcare , canada stands out as spending the highest proportion ( among the 15 countries compared ) on facility - based care . 0 ###LEFT-WALL### 1 canada 0 ###LEFT-WALL### 2 's 0 ###LEFT-WALL### 6 - 0 ###LEFT-WALL### 65 . 1 canada 2 's 2 's 3 spending 3 spending 4 on 4 on 5 facility 6 - 11 care 6 - 12 puts 6 - 23 ; 6 - 35 , 7 based 8 long 7 based 9 - 7 based 11 care 10 term 11 care 11 care 12 puts 12 puts 13 us 12 puts 14 in 14 in 16 middle 15 the 16 middle 16 middle 17 of 17 of 19 pack 18 the 19 pack 19 pack 20 among 20 among 22 countries 21 oecd 22 countries 23 ; 31 care 24 if 25 we 24 if 26 consider 24 if 31 care 25 we 26 consider 26 consider 28 whole 27 the 28 whole 28 whole 29 of 29 of 30 continuing 31 care 33 combining 32 , 33 combining 33 combining 34 ltc 33 combining 35 , 35 , 38 living 35 , 39 and 36 supportive 38 living 37 housing/assisted 38 living 39 and 40 home 39 and 63 based 40 home 46 stands 40 home 63 based 41 - 46 stands 42 based 46 stands 43 healthcare 44 , 43 healthcare 46 stands 45 canada 46 stands 46 stands 47 out 46 stands 51 highest 46 stands 52 proportion 46 stands 62 - 47 out 48 as 48 as 49 spending 50 the 51 highest 51 highest 52 proportion 52 proportion 54 among 52 proportion 60 on 53 ( 54 among 54 among 57 countries 54 among 59 ) 55 the 57 countries 56 15 57 countries 57 countries 58 compared 60 on 61 facility 63 based 64 care predicting the number of new long - term care beds needed in the future is difficult because of shifting needs and changes in service delivery - new stops on the [continuum] [of] care . 0 ###LEFT-WALL### 1 predicting 0 ###LEFT-WALL### 21 and 1 predicting 10 beds 1 predicting 11 needed 1 predicting 21 and 2 the 3 number 3 number 4 of 3 number 10 beds 4 of 10 beds 5 new 8 term 6 long 7 - 6 long 8 term 8 term 10 beds 9 care 10 beds 10 beds 11 needed 11 needed 12 in 12 in 14 future 13 the 14 future 15 is 16 difficult 15 is 21 and 16 difficult 18 of 17 because 18 of 18 of 19 shifting 19 shifting 20 needs 21 and 22 changes 22 changes 23 in 22 changes 25 delivery 24 service 25 delivery 25 delivery 28 stops 26 - 28 stops 27 new 28 stops 28 stops 29 on 28 stops 34 . 29 on 33 care 30 the 33 care it is quite possible to organize a system of care that includes a [continuum] [from] home - based care to supportive housing and assisted living to ltc that [de] - emphasizes this last step . 1 it 2 is 2 is 4 possible 3 quite 4 possible 4 possible 5 to 4 possible 12 includes 5 to 6 organize 6 organize 8 system 7 a 8 system 8 system 9 of 8 system 11 that 8 system 12 includes 9 of 10 care 11 that 12 includes 12 includes 16 home 13 a 16 home 16 home 23 and 17 - 23 and 18 based 19 care 19 care 20 to 19 care 23 and 20 to 22 housing 21 supportive 22 housing 23 and 25 living 23 and 26 to 23 and 28 that 23 and 34 step 23 and 35 . 24 assisted 25 living 26 to 27 ltc 28 that 34 step 30 - 31 emphasizes 31 emphasizes 32 this 31 emphasizes 33 last 31 emphasizes 34 step the increasing elderly population in canada will not bring an apocalypse to the healthcare system , but caring for this population will require [a] redistribution of resources to increase the emphasis on home and community - based services . 0 ###LEFT-WALL### 4 population 0 ###LEFT-WALL### 9 bring 0 ###LEFT-WALL### 17 but 0 ###LEFT-WALL### 29 increase 1 the 4 population 2 increasing 4 population 3 elderly 4 population 4 population 5 in 4 population 7 will 5 in 6 canada 7 will 8 not 7 will 9 bring 9 bring 11 apocalypse 10 an 11 apocalypse 11 apocalypse 12 to 12 to 15 system 13 the 15 system 14 healthcare 15 system 16 , 17 but 17 but 18 caring 17 but 23 require 18 caring 19 for 18 caring 22 will 19 for 21 population 20 this 21 population 22 will 23 require 23 require 25 redistribution 23 require 28 to 25 redistribution 26 of 26 of 27 resources 28 to 29 increase 29 increase 31 emphasis 29 increase 32 on 30 the 31 emphasis 32 on 34 and 33 home 34 and 34 and 35 community 34 and 38 services 36 - 38 services 37 based 38 services 38 services 39 . our planning for just [how] [many] ( [if] any ) new long - term care beds are needed and our assessment of reasonable access to those beds need to rest on a vision for the full spectrum of care and attention to the desires of the population we are trying to serve . 0 ###LEFT-WALL### 19 and 0 ###LEFT-WALL### 28 need 0 ###LEFT-WALL### 53 . 1 our 2 planning 2 planning 3 for 2 planning 19 and 3 for 15 care 4 just 9 any 4 just 14 term 7 ( 9 any 9 any 10 ) 11 new 14 term 12 long 13 - 12 long 14 term 14 term 15 care 15 care 16 beds 15 care 17 are 15 care 18 needed 16 beds 17 are 19 and 21 assessment 19 and 25 to 19 and 28 need 20 our 21 assessment 21 assessment 22 of 22 of 24 access 23 reasonable 24 access 25 to 27 beds 26 those 27 beds 28 need 29 to 28 need 42 to 29 to 30 rest 30 rest 31 on 30 rest 34 for 31 on 33 vision 32 a 33 vision 34 for 37 spectrum 35 the 37 spectrum 36 full 37 spectrum 37 spectrum 38 of 38 of 40 and 39 care 40 and 40 and 41 attention 42 to 44 desires 43 the 44 desires 44 desires 45 of 44 desires 50 trying 44 desires 51 to 44 desires 52 serve 45 of 47 population 46 the 47 population 47 population 48 we 47 population 49 are 48 we 49 are 51 to 52 serve alzheimer 's disease ( ad ) is characterized by a loss of α4β2 and α7 nicotinic acetylcholine receptors ( nachrs ) in the brain and severe memory impairments . 0 ###LEFT-WALL### 3 disease 0 ###LEFT-WALL### 8 characterized 0 ###LEFT-WALL### 25 and 0 ###LEFT-WALL### 29 . 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 characterized 8 characterized 9 by 8 characterized 22 in 9 by 11 loss 10 a 11 loss 11 loss 12 of 12 of 14 and 13 α4β2 14 and 14 and 18 receptors 14 and 20 nachrs 15 α7 18 receptors 16 nicotinic 17 acetylcholine 17 acetylcholine 18 receptors 19 ( 20 nachrs 20 nachrs 21 ) 22 in 24 brain 23 the 24 brain 25 and 27 memory 25 and 28 impairments 26 severe 27 memory 27 memory 28 impairments previously , we found that antibodies elicited against extracellular domain [of] α7 nachr subunit decreased the number of α7 nachrs in the brains of mice and impaired episodic memory . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 27 impaired 0 ###LEFT-WALL### 30 . 1 previously 2 , 1 previously 3 we 3 we 4 found 4 found 5 that 5 that 6 antibodies 5 that 13 nachr 6 antibodies 7 elicited 6 antibodies 8 against 6 antibodies 13 nachr 8 against 12 α7 9 extracellular 10 domain 10 domain 12 α7 13 nachr 14 subunit 14 subunit 15 decreased 14 subunit 19 α7 14 subunit 27 impaired 16 the 17 number 17 number 18 of 17 number 19 α7 18 of 19 α7 19 α7 26 and 20 nachrs 21 in 20 nachrs 26 and 21 in 23 brains 22 the 23 brains 23 brains 24 of 24 of 25 mice 26 and 27 impaired 27 impaired 29 memory 28 episodic 29 memory here we show that antibodies capable to bind α7 ( 1 - 208 ) are present in the blood of both healthy humans and ad patients . 0 ###LEFT-WALL### 2 we 0 ###LEFT-WALL### 3 show 1 here 2 we 2 we 3 show 3 show 4 that 4 that 5 antibodies 4 that 15 are 5 antibodies 6 capable 5 antibodies 12 - 5 antibodies 15 are 6 capable 7 to 7 to 9 α7 8 bind 9 α7 10 ( 12 - 11 1 12 - 12 - 13 208 12 - 14 ) 15 are 16 present 16 present 17 in 17 in 19 blood 18 the 19 blood 19 blood 20 of 20 of 24 and 21 both 24 and 22 healthy 23 humans 23 humans 24 and 24 and 26 patients 24 and 27 . 25 ad 26 patients in healthy individuals , their capacity to compete with [ ( 125 [ )(- i ] - α - bungarotoxin for the binding to α7 ( 1 - 208 ) increased with age . 0 ###LEFT-WALL### 6 capacity 0 ###LEFT-WALL### 31 increased 0 ###LEFT-WALL### 34 . 1 in 3 individuals 1 in 4 , 1 in 6 capacity 2 healthy 3 individuals 5 their 6 capacity 6 capacity 7 to 6 capacity 9 with 6 capacity 17 - 6 capacity 20 bungarotoxin 6 capacity 31 increased 7 to 8 compete 8 compete 9 with 10 [ 17 - 11 ( 14 )(- 12 125 14 )(- 14 )(- 15 i 14 )(- 16 ] 14 )(- 17 - 17 - 18 α 17 - 19 - 19 - 20 bungarotoxin 20 bungarotoxin 21 for 20 bungarotoxin 24 to 20 bungarotoxin 30 ) 21 for 23 binding 22 the 23 binding 24 to 25 α7 25 α7 28 - 26 ( 28 - 27 1 28 - 28 - 29 208 28 - 30 ) 31 increased 32 with 32 with 33 age the level of such antibodies was significantly elevated in children with severe form of obstructive bronchitis and in mice injected with lewis lung carcinoma cells expressing both α4β2 and α7 nachrs . 0 ###LEFT-WALL### 2 level 0 ###LEFT-WALL### 8 elevated 0 ###LEFT-WALL### 32 . 1 the 2 level 2 level 3 of 2 level 6 was 3 of 5 antibodies 4 such 5 antibodies 6 was 8 elevated 7 significantly 8 elevated 8 elevated 9 in 9 in 10 children 10 children 17 and 10 children 20 injected 11 with 13 form 11 with 17 and 12 severe 13 form 13 form 14 of 14 of 16 bronchitis 15 obstructive 16 bronchitis 17 and 18 in 18 in 19 mice 20 injected 21 with 21 with 25 cells 21 with 26 expressing 22 lewis 25 cells 23 lung 24 carcinoma 24 carcinoma 25 cells 26 expressing 31 nachrs 27 both 31 nachrs 28 α4β2 29 and 29 and 30 α7 29 and 31 nachrs elevated antibody levels were accompanied with decreased surface nachrs on the blood lymphocytes of children and [of] mice immunized with α7 ( 1 - 208 ) . 0 ###LEFT-WALL### 3 levels 0 ###LEFT-WALL### 19 immunized 0 ###LEFT-WALL### 27 . 1 elevated 2 antibody 2 antibody 3 levels 3 levels 4 were 4 were 5 accompanied 5 accompanied 6 with 6 with 9 nachrs 6 with 19 immunized 7 decreased 8 surface 8 surface 9 nachrs 9 nachrs 10 on 9 nachrs 14 of 10 on 13 lymphocytes 11 the 13 lymphocytes 12 blood 13 lymphocytes 14 of 16 and 15 children 16 and 16 and 18 mice 19 immunized 20 with 19 immunized 24 - 20 with 21 α7 22 ( 24 - 23 1 24 - 24 - 25 208 24 - 26 ) among ad patients , the level of α7 nachr - specific antibodies was significantly larger in people 62.5 ± 1.5 years old with moderate or severe ad stages ( 15.2 ± 1.3 mmse scores ) compared to those of 76 ± 1.5 years old with the mild ( 22.7 ± 0.1 mmse scores ) ad stage . 0 ###LEFT-WALL### 6 level 0 ###LEFT-WALL### 13 was 0 ###LEFT-WALL### 57 . 1 among 3 patients 1 among 4 , 1 among 6 level 2 ad 3 patients 5 the 6 level 6 level 7 of 6 level 13 was 7 of 12 antibodies 8 α7 12 antibodies 9 nachr 10 - 9 nachr 12 antibodies 11 specific 12 antibodies 13 was 14 significantly 13 was 15 larger 15 larger 16 in 15 larger 23 with 16 in 17 people 17 people 18 62.5 17 people 19 ± 17 people 22 old 18 62.5 19 ± 20 1.5 21 years 21 years 22 old 23 with 28 stages 23 with 36 compared 24 moderate 25 or 25 or 26 severe 25 or 28 stages 27 ad 28 stages 28 stages 34 scores 29 ( 34 scores 30 15.2 34 scores 31 ± 34 scores 32 1.3 34 scores 33 mmse 34 scores 34 scores 35 ) 36 compared 37 to 36 compared 44 old 37 to 38 those 38 those 39 of 39 of 43 years 40 76 43 years 41 ± 43 years 42 1.5 43 years 44 old 45 with 45 with 56 stage 46 the 56 stage 47 mild 53 scores 47 mild 54 ) 47 mild 56 stage 48 ( 53 scores 49 22.7 50 ± 50 ± 53 scores 51 0.1 53 scores 52 mmse 53 scores 53 scores 54 ) 55 ad 56 stage we concluded that α7 ( 1 - 208 ) nachr - specific antibodies found in the human blood are formed as a result of common infections accompanied with the destruction of respiratory epithelium . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 concluded 0 ###LEFT-WALL### 34 . 1 we 2 concluded 2 concluded 3 that 3 that 13 antibodies 3 that 20 formed 4 α7 7 - 4 α7 13 antibodies 5 ( 7 - 6 1 7 - 7 - 8 208 7 - 9 ) 10 nachr 11 - 10 nachr 13 antibodies 12 specific 13 antibodies 13 antibodies 14 found 13 antibodies 15 in 13 antibodies 19 are 15 in 18 blood 16 the 18 blood 17 human 18 blood 19 are 20 formed 20 formed 21 as 21 as 23 result 22 a 23 result 23 result 24 of 24 of 26 infections 25 common 26 infections 26 infections 27 accompanied 26 infections 28 with 26 infections 31 of 28 with 30 destruction 29 the 30 destruction 31 of 33 epithelium 32 respiratory 33 epithelium elevated blood plasma levels of α7 ( 1 - 208 ) nachr - specific antibodies are characteristic for the early - onset ad [and] , therefore , are suggested as one of the risk factors for the development of this form of the disease . 0 ###LEFT-WALL### 4 levels 0 ###LEFT-WALL### 16 are 0 ###LEFT-WALL### 21 - 0 ###LEFT-WALL### 45 . 1 elevated 2 blood 2 blood 4 levels 3 plasma 4 levels 4 levels 5 of 4 levels 16 are 5 of 15 antibodies 6 α7 9 - 6 α7 15 antibodies 7 ( 9 - 8 1 9 - 9 - 10 208 9 - 11 ) 12 nachr 13 - 12 nachr 15 antibodies 14 specific 15 antibodies 16 are 17 characteristic 17 characteristic 18 for 18 for 20 early 19 the 20 early 21 - 23 ad 21 - 29 suggested 22 onset 23 ad 23 ad 28 are 25 , 26 therefore 26 therefore 27 , 26 therefore 28 are 28 are 29 suggested 29 suggested 30 as 29 suggested 36 for 30 as 31 one 31 one 32 of 32 of 35 factors 33 the 35 factors 34 risk 35 factors 36 for 38 development 37 the 38 development 38 development 39 of 38 development 42 of 39 of 41 form 40 this 41 form 42 of 44 disease 43 the 44 disease we have previously shown that 3xtgad mice ( triple - transgenic mice for alzheimer 's disease , harboring ps1 ( m146v ) , aβpp ( swe ) , tau ( p301l ) transgenes ) suffer detrimental changes in some key lymphocyte functions , described as health and longevity markers , with males being more affected than females and showing higher mortality rates . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 4 shown 1 we 2 have 2 have 4 shown 3 previously 4 shown 4 shown 7 mice 4 shown 43 , 5 that 6 3xtgad 6 3xtgad 7 mice 7 mice 12 mice 7 mice 43 , 8 ( 12 mice 9 triple 10 - 9 triple 12 mice 11 transgenic 12 mice 12 mice 13 for 12 mice 34 ) 13 for 16 disease 14 alzheimer 15 's 15 's 16 disease 16 disease 18 harboring 17 , 18 harboring 18 harboring 33 transgenes 18 harboring 34 ) 19 ps1 21 m146v 19 ps1 24 aβpp 19 ps1 33 transgenes 20 ( 21 m146v 21 m146v 22 ) 23 , 24 aβpp 24 aβpp 26 swe 24 aβpp 29 tau 24 aβpp 32 ) 25 ( 26 swe 26 swe 27 ) 28 , 29 tau 29 tau 31 p301l 29 tau 32 ) 30 ( 31 p301l 31 p301l 32 ) 35 suffer 37 changes 35 suffer 43 , 36 detrimental 37 changes 37 changes 38 in 38 in 42 functions 39 some 42 functions 40 key 42 functions 41 lymphocyte 42 functions 43 , 44 described 43 , 45 as 43 , 56 than 43 , 58 and 45 as 47 and 46 health 47 and 47 and 49 markers 47 and 50 , 47 and 51 with 47 and 53 being 48 longevity 49 markers 51 with 52 males 53 being 55 affected 54 more 55 affected 57 females 58 and 58 and 62 rates 58 and 63 . 59 showing 62 rates 60 higher 62 rates 61 mortality 62 rates in the present work , 3xtgad and wild type 129/c57bl6 male and female [non] - and environmentally enriched mice were used . 0 ###LEFT-WALL### 7 and 0 ###LEFT-WALL### 9 type 0 ###LEFT-WALL### 16 and 0 ###LEFT-WALL### 22 . 1 in 3 present 1 in 7 and 2 the 3 present 4 work 5 , 5 , 6 3xtgad 5 , 7 and 7 and 8 wild 7 and 9 type 9 type 10 129/c57bl6 9 type 12 and 11 male 12 and 12 and 13 female 15 - 16 and 16 and 19 mice 16 and 21 used 17 environmentally 18 enriched 18 enriched 19 mice 19 mice 20 were 20 were 21 used the enriched environment ( ee ) began in the adulthood ( 6 months ) and lasted for 5.5 months . 0 ###LEFT-WALL### 3 environment 0 ###LEFT-WALL### 15 and 0 ###LEFT-WALL### 20 . 1 the 3 environment 2 enriched 3 environment 3 environment 5 ee 3 environment 15 and 4 ( 5 ee 5 ee 6 ) 7 began 8 in 7 began 15 and 8 in 10 adulthood 9 the 10 adulthood 10 adulthood 13 months 11 ( 13 months 12 6 13 months 13 months 14 ) 15 and 16 lasted 15 and 17 for 17 for 19 months 18 5.5 19 months the animals were sacrificed at advanced stages of the disease ( 15 month - old [ )(, and spleen , thymus , and plasma were obtained . 0 ###LEFT-WALL### 2 animals 0 ###LEFT-WALL### 4 sacrificed 0 ###LEFT-WALL### 14 - 1 the 2 animals 2 animals 3 were 3 were 4 sacrificed 4 sacrificed 5 at 5 at 7 stages 6 advanced 7 stages 7 stages 8 of 7 stages 13 month 8 of 10 disease 9 the 10 disease 11 ( 13 month 12 15 13 month 13 month 14 - 14 - 15 old 14 - 18 and 14 - 27 . 17 )(, 18 and 18 and 23 and 18 and 26 obtained 19 spleen 20 , 20 , 21 thymus 20 , 23 and 22 , 23 and 23 and 24 plasma 23 and 25 were 25 were 26 obtained the results indicate that 3xtg - ad males are especially benefitted from ee exposure , as shown by the improvement in lymphocyte functional activities such as chemotaxis and natural killer cytotoxicity , as well as in plasma corticosterone levels . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 indicate 0 ###LEFT-WALL### 32 , 0 ###LEFT-WALL### 40 . 1 the 2 results 2 results 3 indicate 3 indicate 8 males 3 indicate 11 benefitted 4 that 5 3xtg 5 3xtg 6 - 5 3xtg 8 males 7 ad 8 males 8 males 9 are 9 are 11 benefitted 10 especially 11 benefitted 11 benefitted 12 from 11 benefitted 18 by 11 benefitted 21 in 11 benefitted 26 as 12 from 14 exposure 13 ee 14 exposure 14 exposure 17 shown 15 , 17 shown 16 as 17 shown 18 by 20 improvement 19 the 20 improvement 21 in 24 activities 22 lymphocyte 24 activities 23 functional 24 activities 25 such 26 as 26 as 28 and 27 chemotaxis 28 and 28 and 31 cytotoxicity 28 and 32 , 29 natural 30 killer 30 killer 31 cytotoxicity 32 , 38 corticosterone 32 , 39 levels 33 as 34 well 33 as 38 corticosterone 35 as 36 in 35 as 38 corticosterone 36 in 37 plasma 38 corticosterone 39 levels by contrast , wild type females seem to be highly sensitive to ee removal , as regards the proliferation capacity of lymphocytes and their intracellular glutathione content . 0 ###LEFT-WALL### 6 females 0 ###LEFT-WALL### 7 seem 1 by 2 contrast 1 by 3 , 1 by 6 females 4 wild 5 type 5 type 6 females 6 females 7 seem 7 seem 8 to 7 seem 9 be 8 to 9 be 9 be 11 sensitive 10 highly 11 sensitive 11 sensitive 12 to 11 sensitive 17 regards 12 to 14 removal 13 ee 14 removal 15 , 17 regards 16 as 17 regards 17 regards 23 and 17 regards 28 . 18 the 20 capacity 19 proliferation 20 capacity 20 capacity 21 of 20 capacity 23 and 21 of 22 lymphocytes 23 and 27 content 24 their 27 content 25 intracellular 26 glutathione 26 glutathione 27 content these results support the relevance of gender differences in ad when screening for new strategies for the control of the disease , and [suggest] that active life , by means of ee , should be maintained until natural death in order to preserve all the positive effects that this strategy exerts on the immune system . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 support 0 ###LEFT-WALL### 56 . 1 these 2 results 2 results 3 support 3 support 5 relevance 3 support 11 when 3 support 37 until 4 the 5 relevance 5 relevance 6 of 5 relevance 9 in 6 of 8 differences 7 gender 8 differences 9 in 10 ad 11 when 27 life 11 when 35 be 12 screening 13 for 12 screening 23 and 13 for 15 strategies 14 new 15 strategies 15 strategies 16 for 15 strategies 19 of 16 for 18 control 17 the 18 control 19 of 21 disease 20 the 21 disease 22 , 23 and 23 and 25 that 23 and 27 life 26 active 27 life 27 life 29 by 27 life 34 should 28 , 29 by 29 by 30 means 29 by 33 , 30 means 31 of 31 of 32 ee 34 should 35 be 35 be 36 maintained 37 until 39 death 38 natural 39 death 39 death 40 in 39 death 52 on 40 in 41 order 41 order 42 to 41 order 43 preserve 42 to 43 preserve 43 preserve 44 all 44 all 45 the 44 all 47 effects 45 the 47 effects 46 positive 47 effects 47 effects 48 that 47 effects 51 exerts 48 that 50 strategy 48 that 51 exerts 49 this 50 strategy 50 strategy 51 exerts 52 on 55 system 53 the 55 system 54 immune 55 system oxidative stress has been associated with normal aging and alzheimer 's disease ( ad ) . 0 ###LEFT-WALL### 2 stress 0 ###LEFT-WALL### 5 associated 0 ###LEFT-WALL### 16 . 1 oxidative 2 stress 2 stress 3 has 3 has 4 been 4 been 5 associated 5 associated 6 with 6 with 9 and 7 normal 8 aging 7 normal 9 and 9 and 12 disease 9 and 14 ad 10 alzheimer 11 's 11 's 12 disease 13 ( 14 ad 14 ad 15 ) however , little is known about oxidative stress in mild cognitive impairment ( mci ) patients who present a high risk for developing ad . 0 ###LEFT-WALL### 3 little 0 ###LEFT-WALL### 5 known 0 ###LEFT-WALL### 25 . 1 however 2 , 1 however 3 little 3 little 4 is 4 is 5 known 5 known 6 about 6 about 8 stress 7 oxidative 8 stress 8 stress 9 in 8 stress 16 patients 8 stress 21 risk 9 in 12 impairment 10 mild 12 impairment 11 cognitive 12 impairment 12 impairment 14 mci 13 ( 14 mci 14 mci 15 ) 16 patients 17 who 16 patients 18 present 16 patients 21 risk 17 who 18 present 18 present 20 high 19 a 20 high 21 risk 22 for 22 for 23 developing 23 developing 24 ad the aim of this study was to investigate plasma production of the lipid peroxidation marker , malonaldehyde ( [mda] [ )( to determine , in erythrocytes , the enzymatic antioxidant activity of [catalase] [,] glutathione [peroxidase] ( gpx ) , glutathione reductase ( gr ) , [and] glutathione s - transferase ( gst [ )(in 33 individuals with mci , [29] with mild probable ad and 26 healthy aged subjects . 0 ###LEFT-WALL### 2 aim 0 ###LEFT-WALL### 6 was 1 the 2 aim 2 aim 3 of 2 aim 6 was 3 of 5 study 4 this 5 study 6 was 7 to 7 to 16 , 8 investigate 10 production 8 investigate 16 , 9 plasma 10 production 10 production 11 of 11 of 15 marker 12 the 15 marker 13 lipid 14 peroxidation 14 peroxidation 15 marker 16 , 23 determine 17 malonaldehyde 22 to 18 ( 22 to 22 to 23 determine 23 determine 25 in 23 determine 29 enzymatic 23 determine 30 antioxidant 24 , 25 in 25 in 26 erythrocytes 25 in 27 , 28 the 29 enzymatic 29 enzymatic 30 antioxidant 30 antioxidant 31 activity 31 activity 32 of 32 of 42 reductase 35 glutathione 38 gpx 35 glutathione 40 , 35 glutathione 42 reductase 37 ( 38 gpx 38 gpx 39 ) 41 glutathione 42 reductase 42 reductase 44 gr 42 reductase 50 - 43 ( 44 gr 44 gr 45 ) 46 , 50 - 48 glutathione 49 s 48 glutathione 50 - 50 - 51 transferase 51 transferase 53 gst 51 transferase 62 with 52 ( 53 gst 53 gst 55 )(in 53 gst 60 , 55 )(in 57 individuals 56 33 57 individuals 57 individuals 58 with 58 with 59 mci 60 , 62 with 62 with 66 and 62 with 71 . 63 mild 65 ad 64 probable 65 ad 65 ad 66 and 66 and 70 subjects 67 26 70 subjects 68 healthy 70 subjects 69 aged 70 subjects gr/gpx activity [ratio] was calculated to better assess antioxidant defenses . 0 ###LEFT-WALL### 2 activity 0 ###LEFT-WALL### 5 calculated 0 ###LEFT-WALL### 11 . 1 gr/gpx 2 activity 2 activity 4 was 4 was 5 calculated 5 calculated 6 to 6 to 8 assess 7 better 8 assess 8 assess 10 defenses 9 antioxidant 10 defenses the relationship between oxidative stress and cognitive performance was also evaluated by the mini mental state examination ( mmse ) . 0 ###LEFT-WALL### 2 relationship 0 ###LEFT-WALL### 11 evaluated 0 ###LEFT-WALL### 21 . 1 the 2 relationship 2 relationship 3 between 2 relationship 9 was 3 between 6 and 4 oxidative 5 stress 5 stress 6 and 6 and 8 performance 7 cognitive 8 performance 9 was 11 evaluated 10 also 11 evaluated 11 evaluated 12 by 12 by 19 mmse 13 the 19 mmse 14 mini 15 mental 15 mental 16 state 16 state 17 examination 17 examination 19 mmse 18 ( 19 mmse 19 mmse 20 ) ad patients showed higher mda levels than both mci and healthy elderly subjects . 0 ###LEFT-WALL### 2 patients 0 ###LEFT-WALL### 3 showed 0 ###LEFT-WALL### 14 . 1 ad 2 patients 2 patients 3 showed 3 showed 6 levels 3 showed 7 than 3 showed 9 mci 3 showed 10 and 4 higher 6 levels 5 mda 6 levels 7 than 8 both 10 and 13 subjects 11 healthy 13 subjects 12 elderly 13 subjects mci subjects also exhibited higher mda levels compared to controls . 0 ###LEFT-WALL### 1 mci 0 ###LEFT-WALL### 2 subjects 0 ###LEFT-WALL### 11 . 1 mci 2 subjects 2 subjects 7 levels 3 also 4 exhibited 4 exhibited 7 levels 5 higher 7 levels 6 mda 7 levels 7 levels 8 compared 8 compared 9 to 9 to 10 controls [catalase] and gpx activity were similar in mci and healthy individuals but higher in ad . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 16 . 2 and 4 activity 2 and 5 were 3 gpx 4 activity 4 activity 5 were 5 were 9 and 6 similar 7 in 6 similar 9 and 7 in 8 mci 9 and 10 healthy 10 healthy 12 but 11 individuals 12 but 12 but 13 higher 13 higher 14 in 14 in 15 ad gr activity was lower in mci [and] ad patients than in healthy aged subjects . 0 ###LEFT-WALL### 2 activity 0 ###LEFT-WALL### 4 lower 0 ###LEFT-WALL### 15 . 1 gr 2 activity 2 activity 3 was 3 was 4 lower 4 lower 5 in 4 lower 9 patients 4 lower 10 than 4 lower 11 in 5 in 6 mci 8 ad 9 patients 11 in 14 subjects 12 healthy 14 subjects 13 aged 14 subjects additionally , gr/gpx [ratio] was higher in healthy aged subjects , intermediate in mci and lower in ad patients . 0 ###LEFT-WALL### 3 gr/gpx 0 ###LEFT-WALL### 5 was 0 ###LEFT-WALL### 11 , 0 ###LEFT-WALL### 20 . 1 additionally 2 , 1 additionally 3 gr/gpx 3 gr/gpx 5 was 5 was 6 higher 6 higher 7 in 7 in 10 subjects 8 healthy 10 subjects 9 aged 10 subjects 11 , 19 patients 12 intermediate 13 in 12 intermediate 15 and 13 in 14 mci 15 and 16 lower 15 and 19 patients 16 lower 17 in 17 in 18 ad no differences in gst activity were detected among the groups . 0 ###LEFT-WALL### 2 differences 0 ###LEFT-WALL### 7 detected 0 ###LEFT-WALL### 11 . 1 no 2 differences 2 differences 3 in 2 differences 6 were 3 in 5 activity 4 gst 5 activity 6 were 7 detected 7 detected 8 among 8 among 10 groups 9 the 10 groups mmse was negatively associated with mda levels ( r = - 0.31 , p = 0.028 ) and positively correlated with gr/gpx [ratio] in ad patients ( r = 0.68 , p < 0.001 ) . 0 ###LEFT-WALL### 1 mmse 0 ###LEFT-WALL### 18 and 0 ###LEFT-WALL### 36 . 1 mmse 18 and 2 was 4 associated 2 was 18 and 3 negatively 4 associated 4 associated 5 with 5 with 6 mda 5 with 7 levels 7 levels 10 = 7 levels 15 = 8 ( 10 = 9 r 10 = 10 = 11 - 11 - 12 0.31 11 - 15 = 13 , 15 = 14 p 15 = 15 = 16 0.028 15 = 17 ) 18 and 20 correlated 18 and 21 with 18 and 24 in 18 and 26 patients 19 positively 20 correlated 21 with 22 gr/gpx 24 in 25 ad 26 patients 29 = 26 patients 33 < 27 ( 29 = 28 r 29 = 29 = 30 0.68 31 , 33 < 32 p 33 < 33 < 34 0.001 33 < 35 ) mda levels were also negatively correlated to gr/gpx [ratio] ( r = - 0.31 , p = 0.029 ) in the ad group . 0 ###LEFT-WALL### 2 levels 0 ###LEFT-WALL### 6 correlated 0 ###LEFT-WALL### 24 . 1 mda 2 levels 2 levels 3 were 3 were 4 also 3 were 6 correlated 5 negatively 6 correlated 6 correlated 7 to 6 correlated 17 = 6 correlated 20 in 7 to 8 gr/gpx 8 gr/gpx 12 = 10 ( 12 = 11 r 12 = 12 = 13 - 13 - 14 0.31 13 - 17 = 15 , 17 = 16 p 17 = 17 = 18 0.029 17 = 19 ) 20 in 23 group 21 the 23 group 22 ad 23 group these results suggest that high lipid peroxidation and decreased antioxidant defenses may be present early in cognitive disorders . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 suggest 0 ###LEFT-WALL### 19 . 1 these 2 results 2 results 3 suggest 3 suggest 4 that 4 that 8 and 4 that 13 be 5 high 6 lipid 6 lipid 7 peroxidation 7 peroxidation 8 and 8 and 11 defenses 8 and 12 may 9 decreased 11 defenses 10 antioxidant 11 defenses 12 may 13 be 13 be 14 present 14 present 15 early 14 present 16 in 16 in 18 disorders 17 cognitive 18 disorders background : asian populations habitually consume a large amount of cruciferous vegetables and other plant - based foods . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 4 populations 2 : 6 consume 2 : 16 - 2 : 19 . 3 asian 4 populations 4 populations 6 consume 5 habitually 6 consume 6 consume 15 plant 7 a 8 large 7 a 15 plant 8 large 9 amount 9 amount 10 of 9 amount 13 and 10 of 12 vegetables 11 cruciferous 12 vegetables 13 and 14 other 13 and 15 plant 16 - 18 foods 17 based 18 foods few epidemiologic investigations have evaluated the potential health effects of these foods in asian populations . 0 ###LEFT-WALL### 3 investigations 0 ###LEFT-WALL### 5 evaluated 0 ###LEFT-WALL### 16 . 1 few 3 investigations 2 epidemiologic 3 investigations 3 investigations 4 have 4 have 5 evaluated 5 evaluated 9 effects 5 evaluated 13 in 6 the 9 effects 7 potential 8 health 8 health 9 effects 9 effects 10 of 10 of 12 foods 11 these 12 foods 13 in 15 populations 14 asian 15 populations objective : we aimed to examine the associations of cruciferous vegetables , noncruciferous vegetables , total vegetables , and total fruit intake with risk of all - cause and cause - specific mortality . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 34 . 2 : 3 we 2 : 4 aimed 2 : 12 , 2 : 31 - 3 we 4 aimed 4 aimed 5 to 4 aimed 6 examine 5 to 6 examine 6 examine 8 associations 7 the 8 associations 8 associations 9 of 9 of 11 vegetables 10 cruciferous 11 vegetables 12 , 29 and 13 noncruciferous 14 vegetables 14 vegetables 15 , 15 , 28 cause 15 , 29 and 16 total 17 vegetables 17 vegetables 19 and 18 , 19 and 19 and 22 intake 19 and 27 - 19 and 28 cause 20 total 21 fruit 21 fruit 22 intake 22 intake 23 with 23 with 24 risk 24 risk 25 of 25 of 26 all 29 and 30 cause 31 - 33 mortality 32 specific 33 mortality design : the analysis included 134,796 chinese adults who participated in 2 population - based , prospective cohort studies : the shanghai women 's health study and the shanghai men 's health study . 0 ###LEFT-WALL### 1 design 0 ###LEFT-WALL### 2 : 2 : 4 analysis 2 : 5 included 2 : 20 : 2 : 31 's 2 : 34 . 3 the 4 analysis 4 analysis 5 included 5 included 8 adults 6 134,796 8 adults 7 chinese 8 adults 8 adults 9 who 8 adults 10 participated 9 who 10 participated 10 participated 11 in 11 in 13 population 12 2 13 population 13 population 15 based 13 population 19 studies 14 - 15 based 15 based 16 , 16 , 19 studies 17 prospective 18 cohort 18 cohort 19 studies 19 studies 20 : 20 : 26 study 20 : 27 and 21 the 23 women 22 shanghai 23 women 23 women 24 's 24 's 26 study 25 health 26 study 27 and 30 men 27 and 31 's 28 the 30 men 29 shanghai 30 men 30 men 31 's 31 's 33 study 32 health 33 study dietary intakes were assessed at baseline through [in] - person interviews by using validated food - frequency questionnaires . 0 ###LEFT-WALL### 2 intakes 0 ###LEFT-WALL### 4 assessed 0 ###LEFT-WALL### 19 . 1 dietary 2 intakes 2 intakes 3 were 3 were 4 assessed 4 assessed 5 at 5 at 18 questionnaires 6 baseline 18 questionnaires 7 through 11 interviews 7 through 16 - 7 through 17 frequency 9 - 11 interviews 10 person 11 interviews 11 interviews 12 by 11 interviews 16 - 12 by 13 using 13 using 15 food 14 validated 15 food 17 frequency 18 questionnaires deaths were ascertained by biennial home visits and linkage with vital statistics registries . 0 ###LEFT-WALL### 1 deaths 0 ###LEFT-WALL### 3 ascertained 0 ###LEFT-WALL### 14 . 1 deaths 2 were 2 were 3 ascertained 3 ascertained 4 by 3 ascertained 10 with 4 by 8 and 5 biennial 6 home 6 home 7 visits 7 visits 8 and 8 and 9 linkage 10 with 12 statistics 10 with 13 registries 11 vital 12 statistics results : we identified 3442 deaths among women during a mean follow - up of 10.2 [y] and 1951 deaths among men during a mean follow - up [of] 4.6 [y] . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 3 we 2 : 4 identified 2 : 13 - 2 : 27 - 3 we 4 identified 4 identified 5 3442 5 3442 6 deaths 5 3442 12 follow 6 deaths 7 among 6 deaths 9 during 6 deaths 12 follow 7 among 8 women 9 during 11 mean 10 a 11 mean 13 - 20 deaths 13 - 26 follow 14 up 20 deaths 15 of 18 and 15 of 20 deaths 16 10.2 18 and 18 and 19 1951 20 deaths 21 among 20 deaths 26 follow 21 among 22 men 22 men 23 during 23 during 25 mean 24 a 25 mean 27 - 28 up 27 - 32 . 28 up 30 4.6 overall , fruit and vegetable intake was inversely associated with risk of total mortality in both women and men , and a dose - response pattern was particularly evident for cruciferous vegetable intake . 0 ###LEFT-WALL### 14 mortality 0 ###LEFT-WALL### 27 was 0 ###LEFT-WALL### 34 . 1 overall 2 , 2 , 3 fruit 2 , 4 and 4 and 5 vegetable 4 and 6 intake 4 and 12 of 4 and 14 mortality 6 intake 7 was 7 was 9 associated 8 inversely 9 associated 9 associated 10 with 10 with 11 risk 11 risk 12 of 13 total 14 mortality 14 mortality 15 in 14 mortality 27 was 15 in 18 and 16 both 17 women 17 women 18 and 18 and 26 pattern 19 men 21 and 20 , 21 and 21 and 23 dose 21 and 24 - 21 and 26 pattern 22 a 23 dose 25 response 26 pattern 27 was 29 evident 28 particularly 29 evident 29 evident 30 for 30 for 33 intake 31 cruciferous 32 vegetable 32 vegetable 33 intake the pooled multivariate hazard ratios ( 95 % cis ) [for] total mortality across increasing quintiles of intake were 1 ( reference ) , 0.91 ( 0.84 , 0.98 ) , 0.88 ( 0.77 , 1.00 ) , 0.85 ( 0.76 , 0.96 ) , [and] 0.78 ( 0.71 , 0.85 ) for cruciferous vegetables ( p < 0.0001 for trend [ )( 0.88 ( 0.79 , 0.97 ) , 0.88 ( 0.79 , 0.98 ) , 0.76 ( 0.62 , 0.92 ) , [and] 0.84 ( 0.69 , 1.00 ) for total vegetables ( p = 0.03 [for] [trend] ) . 0 ###LEFT-WALL### 3 multivariate 0 ###LEFT-WALL### 102 . 1 the 3 multivariate 2 pooled 3 multivariate 3 multivariate 5 ratios 3 multivariate 12 total 3 multivariate 19 were 4 hazard 5 ratios 5 ratios 9 cis 5 ratios 12 total 6 ( 9 cis 7 95 9 cis 8 % 9 cis 9 cis 10 ) 12 total 13 mortality 13 mortality 14 across 14 across 16 quintiles 15 increasing 16 quintiles 16 quintiles 17 of 17 of 18 intake 19 were 20 1 19 were 53 for 19 were 58 < 19 were 60 for 19 were 92 for 20 1 22 reference 20 1 25 0.91 20 1 32 0.88 21 ( 22 reference 22 reference 23 ) 24 , 25 0.91 25 0.91 27 0.84 25 0.91 31 , 26 ( 27 0.84 27 0.84 29 0.98 27 0.84 31 , 28 , 29 0.98 29 0.98 30 ) 31 , 32 0.88 32 0.88 34 0.77 32 0.88 52 ) 33 ( 34 0.77 34 0.77 36 1.00 34 0.77 39 0.85 34 0.77 43 0.96 34 0.77 47 0.78 34 0.77 52 ) 35 , 36 1.00 36 1.00 37 ) 38 , 39 0.85 39 0.85 41 0.76 39 0.85 42 , 40 ( 41 0.76 41 0.76 42 , 42 , 43 0.96 43 0.96 44 ) 45 , 47 0.78 47 0.78 49 0.71 47 0.78 52 ) 48 ( 49 0.71 49 0.71 51 0.85 49 0.71 52 ) 50 , 51 0.85 51 0.85 52 ) 53 for 55 vegetables 54 cruciferous 55 vegetables 56 ( 58 < 57 p 58 < 58 < 59 0.0001 60 for 61 trend 61 trend 64 0.88 61 trend 66 0.79 61 trend 68 0.97 61 trend 71 0.88 65 ( 66 0.79 66 0.79 67 , 67 , 68 0.97 68 0.97 69 ) 70 , 71 0.88 71 0.88 73 0.79 71 0.88 75 0.98 71 0.88 78 0.76 71 0.88 91 ) 72 ( 73 0.79 73 0.79 74 , 74 , 75 0.98 75 0.98 76 ) 77 , 78 0.76 78 0.76 80 0.62 78 0.76 90 1.00 78 0.76 91 ) 79 ( 80 0.62 80 0.62 82 0.92 80 0.62 86 0.84 80 0.62 89 , 81 , 82 0.92 82 0.92 83 ) 84 , 86 0.84 86 0.84 88 0.69 86 0.84 89 , 87 ( 88 0.69 88 0.69 89 , 89 , 90 1.00 90 1.00 91 ) 92 for 94 vegetables 93 total 94 vegetables 94 vegetables 97 = 95 ( 97 = 96 p 97 = 97 = 98 0.03 97 = 101 ) the inverse associations were primarily related to cardiovascular disease mortality but not to cancer mortality . 0 ###LEFT-WALL### 3 associations 0 ###LEFT-WALL### 6 related 0 ###LEFT-WALL### 16 . 1 the 3 associations 2 inverse 3 associations 3 associations 4 were 4 were 6 related 5 primarily 6 related 6 related 11 but 7 to 10 mortality 7 to 11 but 8 cardiovascular 9 disease 9 disease 10 mortality 11 but 12 not 11 but 13 to 13 to 15 mortality 14 cancer 15 mortality conclusion : our findings support recommendations to increase consumption of vegetables , particularly cruciferous vegetables , and fruit to promote cardiovascular health and overall longevity . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 8 increase 0 ###LEFT-WALL### 26 . 2 : 4 findings 2 : 5 support 3 our 4 findings 4 findings 5 support 5 support 6 recommendations 5 support 7 to 7 to 8 increase 8 increase 17 and 8 increase 19 to 9 consumption 10 of 9 consumption 12 , 10 of 11 vegetables 12 , 15 vegetables 12 , 17 and 13 particularly 14 cruciferous 14 cruciferous 15 vegetables 16 , 17 and 17 and 18 fruit 19 to 20 promote 20 promote 23 and 21 cardiovascular 22 health 22 health 23 and 23 and 24 overall 23 and 25 longevity background : although long - chain omega - 3 fatty acid ( n - 3 fa ) consumption estimated via food [-] frequency questionnaires has been associated with a higher incidence of diabetes , limited prospective data on diabetes risk [are] available that use objective biomarkers of [n] - 3 fas . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 34 , 0 ###LEFT-WALL### 52 . 1 background 2 : 2 : 3 although 3 although 18 consumption 4 long 7 omega 4 long 18 consumption 5 - 7 omega 6 chain 7 omega 7 omega 11 acid 7 omega 17 ) 8 - 11 acid 9 3 11 acid 10 fatty 11 acid 11 acid 14 - 11 acid 17 ) 12 ( 14 - 13 n 14 - 14 - 16 fa 14 - 17 ) 15 3 16 fa 18 consumption 19 estimated 18 consumption 34 , 19 estimated 20 via 20 via 24 questionnaires 21 food 23 frequency 23 frequency 24 questionnaires 25 has 26 been 25 has 34 , 26 been 27 associated 27 associated 28 with 28 with 31 incidence 29 a 31 incidence 30 higher 31 incidence 31 incidence 32 of 32 of 33 diabetes 34 , 35 limited 35 limited 37 data 36 prospective 37 data 37 data 38 on 37 data 43 that 37 data 44 use 38 on 40 risk 39 diabetes 40 risk 40 risk 42 available 43 that 44 use 44 use 46 biomarkers 45 objective 46 biomarkers 46 biomarkers 47 of 47 of 51 fas 49 - 50 3 50 3 51 fas objective : we sought to examine the relation between plasma phospholipid n - 3 fas and incident diabetes . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 2 : 3 we 2 : 4 sought 2 : 19 . 3 we 4 sought 4 sought 5 to 4 sought 6 examine 5 to 6 examine 6 examine 8 relation 6 examine 9 between 7 the 8 relation 9 between 18 diabetes 10 plasma 18 diabetes 11 phospholipid 18 diabetes 12 n 13 - 13 - 14 3 13 - 18 diabetes 15 fas 16 and 16 and 17 incident 16 and 18 diabetes design : we prospectively analyzed data in 3088 older men and women ( mean age [:] 75 [y] ) from the cardiovascular health study ( 1992 - 2007 ) . 0 ###LEFT-WALL### 1 design 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 30 . 2 : 3 we 2 : 5 analyzed 3 we 5 analyzed 4 prospectively 5 analyzed 5 analyzed 6 data 5 analyzed 27 - 6 data 7 in 6 data 20 from 7 in 11 and 8 3088 10 men 9 older 10 men 10 men 11 and 11 and 12 women 11 and 15 age 13 ( 15 age 14 mean 15 age 15 age 17 75 15 age 19 ) 20 from 24 study 21 the 24 study 22 cardiovascular 23 health 23 health 24 study 25 ( 27 - 26 1992 27 - 27 - 28 2007 27 - 29 ) plasma phospholipid n - 3 fas [were] measured by using gas chromatography , and incident diabetes was ascertained by using information on hypoglycemic agents and serum glucose . 0 ###LEFT-WALL### 1 plasma 0 ###LEFT-WALL### 18 ascertained 2 phospholipid 16 diabetes 2 phospholipid 17 was 2 phospholipid 18 ascertained 3 n 4 - 4 - 5 3 4 - 16 diabetes 6 fas 8 measured 6 fas 14 and 8 measured 9 by 9 by 10 using 10 using 12 chromatography 11 gas 12 chromatography 13 , 14 and 14 and 15 incident 14 and 16 diabetes 16 diabetes 17 was 18 ascertained 19 by 18 ascertained 22 on 18 ascertained 28 . 19 by 21 information 20 using 21 information 22 on 25 and 23 hypoglycemic 24 agents 24 agents 25 and 25 and 27 glucose 26 serum 27 glucose we used cox proportional hazards models to estimate multivariable - adjusted relative risks . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 used 0 ###LEFT-WALL### 14 . 1 we 2 used 2 used 6 models 2 used 7 to 2 used 8 estimate 3 cox 6 models 4 proportional 5 hazards 5 hazards 6 models 7 to 8 estimate 8 estimate 13 risks 9 multivariable 10 - 9 multivariable 13 risks 11 adjusted 13 risks 12 relative 13 risks results : during a median follow - up of 10.6 [y] , 204 new cases of diabetes occurred . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 6 follow 2 : 7 - 3 during 5 median 3 during 6 follow 4 a 5 median 7 - 15 cases 7 - 18 occurred 7 - 19 . 8 up 15 cases 9 of 10 10.6 9 of 12 , 9 of 15 cases 13 204 15 cases 14 new 15 cases 15 cases 16 of 15 cases 18 occurred 16 of 17 diabetes corresponding relative risks ( 95 % cis ) for phospholipid α - linolenic acid ( ala ) were 1.0 ( reference ) , 0.93 ( 0.65 , 1.34 ) , 0.99 ( 0.68 , 1.44 ) , [and] 0.57 ( 0.36 , 0.90 ) ( p [for] [trend] = 0.03 ) . 0 ###LEFT-WALL### 1 corresponding 0 ###LEFT-WALL### 18 were 0 ###LEFT-WALL### 52 . 1 corresponding 3 risks 1 corresponding 9 for 1 corresponding 18 were 2 relative 3 risks 3 risks 7 cis 4 ( 7 cis 5 95 7 cis 6 % 7 cis 7 cis 8 ) 9 for 11 α 10 phospholipid 11 α 11 α 14 acid 12 - 14 acid 13 linolenic 14 acid 14 acid 16 ala 14 acid 17 ) 15 ( 16 ala 16 ala 17 ) 18 were 19 1.0 19 1.0 21 reference 19 1.0 24 0.93 19 1.0 31 0.99 20 ( 21 reference 21 reference 22 ) 23 , 24 0.93 24 0.93 26 0.65 24 0.93 29 ) 25 ( 26 0.65 26 0.65 28 1.34 26 0.65 29 ) 27 , 28 1.34 28 1.34 29 ) 30 , 31 0.99 31 0.99 33 0.68 31 0.99 39 0.57 31 0.99 51 ) 32 ( 33 0.68 33 0.68 35 1.44 33 0.68 37 , 34 , 35 1.44 35 1.44 36 ) 37 , 39 0.57 39 0.57 41 0.36 39 0.57 51 ) 40 ( 41 0.36 41 0.36 43 0.90 41 0.36 49 = 41 0.36 51 ) 42 , 43 0.90 43 0.90 44 ) 45 ( 49 = 46 p 49 = 49 = 50 0.03 49 = 51 ) conclusions : with the use of objective biomarkers , long - chain n - 3 fas [and] ala were not associated with a higher incidence of diabetes . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 18 ala 2 : 21 associated 2 : 28 . 3 with 5 use 3 with 9 , 3 with 18 ala 4 the 5 use 5 use 6 of 6 of 8 biomarkers 7 objective 8 biomarkers 10 long 11 - 10 long 18 ala 12 chain 18 ala 13 n 14 - 14 - 15 3 14 - 18 ala 16 fas 18 ala 18 ala 19 were 19 were 20 not 19 were 21 associated 21 associated 22 with 22 with 25 incidence 23 a 25 incidence 24 higher 25 incidence 25 incidence 26 of 26 of 27 diabetes individuals with the highest concentrations of both types of fas had lower risk of diabetes . 0 ###LEFT-WALL### 1 individuals 0 ###LEFT-WALL### 11 had 0 ###LEFT-WALL### 16 . 1 individuals 2 with 1 individuals 6 of 1 individuals 11 had 2 with 5 concentrations 3 the 4 highest 3 the 5 concentrations 6 of 10 fas 7 both 8 types 8 types 9 of 8 types 10 fas 9 of 10 fas 11 had 13 risk 12 lower 13 risk 13 risk 14 of 14 of 15 diabetes background : rapid aging of the population worldwide necessitates a heightened concern about preventing [cognitive] [decline] . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 14 preventing 0 ###LEFT-WALL### 17 . 2 : 3 rapid 3 rapid 4 aging 3 rapid 14 preventing 4 aging 5 of 4 aging 9 necessitates 5 of 7 population 6 the 7 population 8 worldwide 9 necessitates 9 necessitates 12 concern 9 necessitates 13 about 10 a 12 concern 11 heightened 12 concern 13 about 14 preventing objective : we investigated the effects of b [vitamins] and omega - 3 ( n - 3 ) fatty acid supplementation on cognition in a high - risk population . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 30 . 2 : 3 we 2 : 4 investigated 3 we 4 investigated 4 investigated 21 supplementation 5 the 6 effects 6 effects 7 of 6 effects 10 and 7 of 8 b 10 and 11 omega 10 and 13 3 10 and 21 supplementation 12 - 13 3 13 3 16 - 13 3 18 ) 14 ( 16 - 15 n 16 - 16 - 17 3 16 - 18 ) 19 fatty 20 acid 20 acid 21 supplementation 21 supplementation 22 on 21 supplementation 24 in 22 on 23 cognition 24 in 29 population 25 a 26 high 25 a 29 population 26 high 27 - 26 high 29 population 28 risk 29 population design : this was an ancillary study of the su.fol.om3 ( supplementation with folate , vitamins b - [6] and b - 12 [and/or] omega - 3 fatty acids ) secondary prevention trial conducted in france between 2003 and 2009 . 0 ###LEFT-WALL### 1 design 0 ###LEFT-WALL### 2 : 2 : 3 this 2 : 4 was 2 : 41 . 3 this 4 was 4 was 20 and 4 was 35 in 4 was 37 between 5 an 6 ancillary 5 an 7 study 6 ancillary 7 study 7 study 8 of 7 study 20 and 8 of 10 su.fol.om3 9 the 10 su.fol.om3 10 su.fol.om3 12 supplementation 10 su.fol.om3 16 vitamins 11 ( 12 supplementation 12 supplementation 13 with 12 supplementation 15 , 13 with 14 folate 15 , 16 vitamins 16 vitamins 17 b 16 vitamins 18 - 20 and 33 trial 20 and 34 conducted 21 b 22 - 22 - 23 12 22 - 33 trial 25 omega 29 acids 25 omega 32 prevention 26 - 29 acids 27 3 29 acids 28 fatty 29 acids 29 acids 30 ) 31 secondary 32 prevention 32 prevention 33 trial 35 in 36 france 37 between 39 and 38 2003 39 and 39 and 40 2009 the present sample included 1748 men and women aged 45 - 80 [y] with a history of myocardial infarction , unstable angina , or ischemic stroke and who were recruited via a network of 417 physicians . 0 ###LEFT-WALL### 3 sample 0 ###LEFT-WALL### 4 included 0 ###LEFT-WALL### 7 and 0 ###LEFT-WALL### 37 . 1 the 3 sample 2 present 3 sample 3 sample 4 included 4 included 6 men 5 1748 6 men 7 and 27 and 7 and 30 recruited 8 women 9 aged 8 women 17 of 8 women 20 , 9 aged 11 - 9 aged 14 with 10 45 11 - 11 - 12 80 14 with 16 history 15 a 16 history 17 of 19 infarction 18 myocardial 19 infarction 20 , 22 angina 20 , 24 or 21 unstable 22 angina 23 , 24 or 24 or 26 stroke 24 or 27 and 25 ischemic 26 stroke 27 and 28 who 27 and 29 were 29 were 30 recruited 30 recruited 31 via 31 via 33 network 32 a 33 network 33 network 34 of 34 of 36 physicians 35 417 36 physicians cognitive function [after] 4 [y] of supplementation was assessed with the french version of the modified telephone interview for cognitive status . 0 ###LEFT-WALL### 2 function 0 ###LEFT-WALL### 9 assessed 0 ###LEFT-WALL### 22 . 1 cognitive 2 function 2 function 4 4 2 function 6 of 2 function 8 was 6 of 7 supplementation 8 was 9 assessed 9 assessed 10 with 9 assessed 19 for 10 with 13 version 11 the 13 version 12 french 13 version 13 version 14 of 14 of 18 interview 15 the 18 interview 16 modified 18 interview 17 telephone 18 interview 19 for 21 status 20 cognitive 21 status results : no significant main effects [of] group assignment [on] cognitive function were found ; however , we found some evidence of disease history - and age - specific effects . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 12 function 2 : 14 found 2 : 15 ; 2 : 28 - 3 no 12 function 4 significant 5 main 5 main 12 function 6 effects 8 group 8 group 12 function 9 assignment 12 function 11 cognitive 12 function 12 function 13 were 13 were 14 found 15 ; 18 we 15 ; 19 found 16 however 17 , 16 however 18 we 18 we 19 found 19 found 21 evidence 20 some 21 evidence 21 evidence 22 of 22 of 26 and 23 disease 24 history 24 history 26 and 25 - 26 and 26 and 27 age 28 - 30 effects 28 - 31 . 29 specific 30 effects in the subgroup with prior stroke , for example , participants assigned to [receive] b vitamins plus omega - 3 fatty acids were significantly less likely to have a decreased score on the temporal orientation task than were those assigned to receive placebo ( odds ratio [:] 0.43 [;] 95 % ci [:] 0.21 , 0.86 ) . 0 ###LEFT-WALL### 11 participants 0 ###LEFT-WALL### 12 assigned 1 in 3 subgroup 1 in 7 , 1 in 11 participants 2 the 3 subgroup 3 subgroup 4 with 4 with 6 stroke 5 prior 6 stroke 7 , 8 for 8 for 9 example 8 for 10 , 8 for 11 participants 11 participants 12 assigned 12 assigned 13 to 12 assigned 16 vitamins 12 assigned 17 plus 13 to 15 b 17 plus 18 omega 18 omega 22 acids 18 omega 23 were 19 - 20 3 20 3 22 acids 21 fatty 22 acids 22 acids 23 were 23 were 25 less 23 were 27 to 23 were 32 on 24 significantly 25 less 26 likely 27 to 27 to 28 have 28 have 31 score 29 a 31 score 30 decreased 31 score 32 on 35 orientation 33 the 35 orientation 34 temporal 35 orientation 35 orientation 36 task 35 orientation 40 assigned 36 task 38 were 37 than 38 were 38 were 39 those 39 those 40 assigned 40 assigned 41 to 41 to 42 receive 42 receive 43 placebo 43 placebo 52 ci 44 ( 52 ci 45 odds 52 ci 46 ratio 52 ci 48 0.43 52 ci 50 95 52 ci 51 % 52 ci 52 ci 54 0.21 52 ci 56 0.86 52 ci 58 . 55 , 56 0.86 56 0.86 57 ) conclusions : if present , dietary effects on cognition are likely group [-] specific . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 15 . 1 conclusions 2 : 2 : 3 if 2 : 14 specific 3 if 7 effects 3 if 12 group 4 present 5 , 4 present 7 effects 6 dietary 7 effects 7 effects 8 on 7 effects 10 are 8 on 9 cognition 10 are 12 group 11 likely 12 group these results could be useful in interventions aimed at preventing cognitive decline [in] high - risk individuals . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 4 be 0 ###LEFT-WALL### 18 . 1 these 2 results 2 results 3 could 3 could 4 be 4 be 5 useful 5 useful 6 in 6 in 7 interventions 7 interventions 8 aimed 8 aimed 9 at 9 at 10 preventing 10 preventing 17 individuals 11 cognitive 12 decline 12 decline 17 individuals 14 high 15 - 14 high 17 individuals 16 risk 17 individuals this trial is registered at controlled [-] trials.com as isrctn41926726 . 0 ###LEFT-WALL### 2 trial 0 ###LEFT-WALL### 4 registered 0 ###LEFT-WALL### 11 . 1 this 2 trial 2 trial 3 is 3 is 4 registered 4 registered 5 at 4 registered 9 as 5 at 8 trials.com 6 controlled 8 trials.com 9 as 10 isrctn41926726 background : folic acid ( fa ) fortification of food created the need to determine whether fortification elevated concentrations of unmetabolized fa in plasma and whether this form of the vitamin in blood is associated with adverse health outcomes . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 40 . 1 background 2 : 2 : 3 folic 2 : 14 to 3 folic 8 fortification 3 folic 11 created 4 acid 6 fa 4 acid 8 fortification 5 ( 6 fa 6 fa 7 ) 8 fortification 9 of 8 fortification 11 created 9 of 10 food 11 created 13 need 12 the 13 need 14 to 15 determine 15 determine 16 whether 15 determine 28 form 15 determine 35 associated 16 whether 17 fortification 16 whether 18 elevated 17 fortification 18 elevated 18 elevated 19 concentrations 18 elevated 23 in 19 concentrations 20 of 20 of 22 fa 21 unmetabolized 22 fa 23 in 25 and 24 plasma 25 and 25 and 26 whether 27 this 28 form 28 form 29 of 28 form 34 is 29 of 31 vitamin 30 the 31 vitamin 31 vitamin 32 in 32 in 33 blood 34 is 35 associated 35 associated 36 with 36 with 38 health 36 with 39 outcomes 37 adverse 38 health objective : the objective of this research was to devise a simple , rapid method for the measurement of unmetabolized plasma fa in epidemiologic studies . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 26 . 1 objective 2 : 2 : 4 objective 3 the 4 objective 4 objective 5 of 4 objective 7 research 4 objective 10 devise 5 of 6 this 7 research 8 was 8 was 9 to 8 was 10 devise 9 to 10 devise 10 devise 15 method 11 a 12 simple 11 a 15 method 12 simple 13 , 12 simple 15 method 14 rapid 15 method 15 method 16 for 15 method 19 of 16 for 18 measurement 17 the 18 measurement 19 of 22 fa 20 unmetabolized 21 plasma 21 plasma 22 fa 22 fa 23 in 23 in 25 studies 24 epidemiologic 25 studies design : we previously used the affinity/hplc with electrochemical detection method to measure folate distribution in human plasma and red blood cells ( rbcs ) . 0 ###LEFT-WALL### 1 design 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 26 . 2 : 3 we 2 : 5 used 3 we 5 used 4 previously 5 used 5 used 7 affinity/hplc 5 used 8 with 5 used 12 to 5 used 19 and 6 the 7 affinity/hplc 8 with 11 method 9 electrochemical 10 detection 10 detection 11 method 12 to 19 and 13 measure 15 distribution 13 measure 19 and 14 folate 15 distribution 15 distribution 16 in 16 in 18 plasma 17 human 18 plasma 19 and 20 red 20 red 22 cells 21 blood 22 cells 22 cells 24 rbcs 23 ( 24 rbcs 24 rbcs 25 ) we modified this method with the inclusion of synthetic ethyltetrahydrofolate as an internal standard and with the use of 2 affinity columns connected in parallel to the analytic column through a switching valve to allow one column to be loaded while the other column was eluted into the analytic column . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 51 . 1 we 2 modified 2 modified 4 method 2 modified 30 through 2 modified 34 to 3 this 4 method 4 method 15 and 4 method 19 of 5 with 7 inclusion 5 with 15 and 6 the 7 inclusion 7 inclusion 8 of 8 of 10 ethyltetrahydrofolate 9 synthetic 10 ethyltetrahydrofolate 10 ethyltetrahydrofolate 11 as 11 as 14 standard 12 an 13 internal 12 an 14 standard 13 internal 14 standard 15 and 16 with 16 with 18 use 17 the 18 use 19 of 22 columns 20 2 22 columns 21 affinity 22 columns 22 columns 23 connected 22 columns 25 parallel 23 connected 24 in 25 parallel 26 to 26 to 29 column 27 the 29 column 28 analytic 29 column 30 through 33 valve 31 a 33 valve 32 switching 33 valve 34 to 35 allow 35 allow 37 column 35 allow 38 to 35 allow 40 loaded 36 one 37 column 38 to 39 be 39 be 40 loaded 40 loaded 41 while 40 loaded 47 into 41 while 44 column 41 while 46 eluted 42 the 43 other 43 other 44 column 44 column 45 was 45 was 46 eluted 47 into 50 column 48 the 50 column 49 analytic 50 column results : we identified fa and 5 - methyltetrahydrofolate ( 5 - mthf ) by retention time and characteristic response across the channels of the electrochemical detector . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 28 . 2 : 3 we 2 : 4 identified 2 : 6 and 2 : 9 methyltetrahydrofolate 3 we 4 identified 4 identified 5 fa 6 and 7 5 6 and 8 - 7 5 8 - 8 - 9 methyltetrahydrofolate 9 methyltetrahydrofolate 12 - 9 methyltetrahydrofolate 15 by 9 methyltetrahydrofolate 21 across 10 ( 12 - 11 5 12 - 12 - 13 mthf 12 - 14 ) 15 by 18 and 16 retention 17 time 17 time 18 and 18 and 20 response 19 characteristic 20 response 21 across 23 channels 22 the 23 channels 23 channels 24 of 24 of 27 detector 25 the 27 detector 26 electrochemical 27 detector limits of detection were 0.034 pmol for 5 [-] mthf and 0.027 pmol for fa per injection , and the recovery was 92.2 % ( 5 - mthf [ )(and 98.9 % ( fa ) . 0 ###LEFT-WALL### 1 limits 0 ###LEFT-WALL### 4 were 0 ###LEFT-WALL### 19 and 0 ###LEFT-WALL### 36 . 1 limits 2 of 1 limits 4 were 2 of 3 detection 4 were 13 pmol 5 0.034 6 pmol 5 0.034 11 and 6 pmol 7 for 6 pmol 10 mthf 7 for 8 5 11 and 12 0.027 11 and 13 pmol 13 pmol 14 for 14 for 15 fa 15 fa 16 per 16 per 17 injection 18 , 19 and 19 and 21 recovery 19 and 22 was 20 the 21 recovery 21 recovery 22 was 22 was 32 % 23 92.2 24 % 23 92.2 30 )(and 24 % 26 5 24 % 28 mthf 25 ( 26 5 26 5 27 - 30 )(and 31 98.9 30 )(and 32 % 32 % 34 fa 33 ( 34 fa 34 fa 35 ) cvs for samples were 8.1 % ( within day ) and 6.8 % ( between day [ )(for 5 - mthf [and] 3.2 % ( within day ) [and] [5.9] [%] ( between day ) for fa . 0 ###LEFT-WALL### 1 cvs 0 ###LEFT-WALL### 4 were 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 38 . 1 cvs 2 for 1 cvs 4 were 2 for 3 samples 4 were 6 % 5 8.1 6 % 6 % 8 within 7 ( 8 within 8 within 9 day 8 within 10 ) 11 and 13 % 11 and 21 mthf 12 6.8 13 % 13 % 15 between 13 % 21 mthf 14 ( 15 between 15 between 16 day 15 between 20 - 16 day 18 )(for 18 )(for 19 5 21 mthf 24 % 21 mthf 36 for 23 3.2 24 % 24 % 26 within 24 % 33 between 25 ( 26 within 26 within 27 day 26 within 28 ) 32 ( 33 between 33 between 34 day 33 between 35 ) 36 for 37 fa total folate with the use of this method correlated highly [(] r ( 2 [ )(= 0.98 , p < 0.001 ) with values from the microbial assay . 0 ###LEFT-WALL### 1 total 0 ###LEFT-WALL### 29 . 1 total 2 folate 1 total 3 with 3 with 5 use 4 the 5 use 5 use 6 of 6 of 8 method 7 this 8 method 8 method 9 correlated 9 correlated 10 highly 9 correlated 16 )(= 9 correlated 20 < 9 correlated 23 with 12 r 16 )(= 13 ( 16 )(= 14 2 16 )(= 16 )(= 17 0.98 16 )(= 18 , 18 , 20 < 19 p 20 < 20 < 21 0.001 20 < 22 ) 23 with 24 values 24 values 25 from 25 from 28 assay 26 the 28 assay 27 microbial 28 assay the run time for the method was 30 min per sample . 0 ###LEFT-WALL### 3 time 0 ###LEFT-WALL### 7 was 0 ###LEFT-WALL### 12 . 1 the 3 time 2 run 3 time 3 time 4 for 3 time 7 was 4 for 6 method 5 the 6 method 7 was 9 min 8 30 9 min 9 min 10 per 10 per 11 sample researchers can use this method with longer run times to measure the distribution of folate forms in rbcs . 0 ###LEFT-WALL### 1 researchers 0 ###LEFT-WALL### 3 use 0 ###LEFT-WALL### 19 . 1 researchers 2 can 2 can 3 use 3 use 5 method 3 use 6 with 3 use 10 to 3 use 11 measure 4 this 5 method 6 with 9 times 7 longer 8 run 8 run 9 times 10 to 11 measure 11 measure 13 distribution 11 measure 17 in 12 the 13 distribution 13 distribution 14 of 14 of 16 forms 15 folate 16 forms 17 in 18 rbcs conclusion : this updated method allows efficient analysis of folate forms in human plasma and tissues without the loss of sensitivity or precision . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 5 method 2 : 6 allows 2 : 24 . 3 this 5 method 4 updated 5 method 5 method 6 allows 6 allows 8 analysis 6 allows 11 forms 6 allows 12 in 6 allows 17 without 7 efficient 8 analysis 8 analysis 9 of 9 of 10 folate 12 in 15 and 13 human 14 plasma 14 plasma 15 and 15 and 16 tissues 17 without 19 loss 18 the 19 loss 19 loss 20 of 20 of 22 or 21 sensitivity 22 or 22 or 23 precision none objective : to determine the patterns of diffusivity associated with cognitive domain functions in older adults without dementia . 0 ###LEFT-WALL### 1 none 0 ###LEFT-WALL### 10 associated 0 ###LEFT-WALL### 20 . 1 none 2 objective 1 none 5 determine 1 none 10 associated 2 objective 3 : 3 : 4 to 3 : 5 determine 4 to 5 determine 5 determine 7 patterns 6 the 7 patterns 7 patterns 8 of 8 of 9 diffusivity 10 associated 11 with 10 associated 15 in 11 with 14 functions 12 cognitive 13 domain 13 domain 14 functions 15 in 17 adults 16 older 17 adults 17 adults 18 without 18 without 19 dementia methods : we studied older adults without dementia ( n = 220 ) who underwent neuropsychometric testing and a diffusion tensor [imaging] ( dti ) examination at 3 t in a cross - sectional study . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 36 . 2 : 3 we 2 : 4 studied 2 : 33 - 3 we 4 studied 4 studied 6 adults 4 studied 27 at 4 studied 30 in 5 older 6 adults 6 adults 7 without 6 adults 14 who 6 adults 15 underwent 7 without 8 dementia 8 dementia 11 = 9 ( 11 = 10 n 11 = 11 = 12 220 11 = 13 ) 14 who 15 underwent 15 underwent 18 and 16 neuropsychometric 17 testing 17 testing 18 and 18 and 26 examination 19 a 20 diffusion 19 a 26 examination 20 diffusion 26 examination 21 tensor 24 dti 21 tensor 26 examination 23 ( 24 dti 24 dti 25 ) 27 at 29 t 28 3 29 t 30 in 32 cross 31 a 32 cross 33 - 35 study 34 sectional 35 study memory , language , attention/executive function , and visual - spatial processing domains were assessed within 4 months of the mri examination . 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 15 assessed 0 ###LEFT-WALL### 23 . 1 memory 2 , 2 , 3 language 2 , 4 , 4 , 6 function 4 , 8 and 5 attention/executive 6 function 7 , 8 and 8 and 13 domains 8 and 14 were 9 visual 10 - 9 visual 13 domains 11 spatial 13 domains 12 processing 13 domains 14 were 15 assessed 15 assessed 16 within 16 within 18 months 17 4 18 months 18 months 19 of 19 of 22 examination 20 the 22 examination 21 mri 22 examination a fluid - attenuated inversion recovery - based dti sequence that enabled uncontaminated cortical diffusion measurements was performed . 0 ###LEFT-WALL### 10 sequence 0 ###LEFT-WALL### 18 performed 0 ###LEFT-WALL### 19 . 1 a 2 fluid 1 a 10 sequence 2 fluid 6 recovery 2 fluid 7 - 2 fluid 10 sequence 3 - 6 recovery 4 attenuated 5 inversion 5 inversion 6 recovery 6 recovery 7 - 8 based 10 sequence 9 dti 10 sequence 10 sequence 11 that 10 sequence 12 enabled 10 sequence 17 was 11 that 12 enabled 12 enabled 16 measurements 13 uncontaminated 15 diffusion 14 cortical 15 diffusion 15 diffusion 16 measurements 17 was 18 performed associations between cortical mean diffusivity ( md ) and cognitive function were tested using voxel - based regression analysis . 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 13 tested 0 ###LEFT-WALL### 20 . 1 associations 2 between 1 associations 9 and 2 between 5 diffusivity 3 cortical 4 mean 4 mean 5 diffusivity 5 diffusivity 7 md 6 ( 7 md 7 md 8 ) 9 and 11 function 9 and 12 were 10 cognitive 11 function 12 were 13 tested 13 tested 14 using 14 using 19 analysis 15 voxel 16 - 15 voxel 18 regression 17 based 18 regression 18 regression 19 analysis association between tract diffusivity and cognitive function was tested with regions of interest drawn on color - coded fractional anisotropy ( fa ) maps . 0 ###LEFT-WALL### 1 association 0 ###LEFT-WALL### 9 tested 0 ###LEFT-WALL### 17 - 1 association 2 between 1 association 8 was 2 between 5 and 3 tract 4 diffusivity 4 diffusivity 5 and 5 and 7 function 6 cognitive 7 function 8 was 9 tested 9 tested 10 with 10 with 11 regions 11 regions 12 of 12 of 13 interest 13 interest 14 drawn 14 drawn 15 on 15 on 16 color 17 - 24 maps 17 - 25 . 18 coded 24 maps 19 fractional 24 maps 20 anisotropy 22 fa 20 anisotropy 23 ) 20 anisotropy 24 maps 21 ( 22 fa 22 fa 23 ) results : memory function was associated with the medial temporal lobe cortical md on voxel - based analysis ( p < 0.001 , corrected for multiple comparisons [ )(, and inferior longitudinal fasciculus and posterior and anterior cingulum fa on tract - based analysis ( p < 0.001 ) . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 6 associated 2 : 4 function 3 memory 4 function 4 function 5 was 5 was 6 associated 6 associated 7 with 6 associated 14 on 7 with 9 medial 7 with 13 md 8 the 9 medial 10 temporal 11 lobe 11 lobe 13 md 12 cortical 13 md 14 on 18 analysis 15 voxel 16 - 15 voxel 18 analysis 17 based 18 analysis 18 analysis 21 < 19 ( 21 < 20 p 21 < 21 < 22 0.001 22 0.001 24 corrected 23 , 24 corrected 24 corrected 25 for 25 for 34 and 26 multiple 27 comparisons 27 comparisons 30 and 29 )(, 30 and 30 and 33 fasciculus 30 and 34 and 31 inferior 33 fasciculus 32 longitudinal 33 fasciculus 34 and 39 fa 34 and 40 on 34 and 44 analysis 35 posterior 36 and 36 and 37 anterior 36 and 39 fa 38 cingulum 39 fa 40 on 41 tract 42 - 44 analysis 43 based 44 analysis 44 analysis 47 < 44 analysis 50 . 45 ( 47 < 46 p 47 < 47 < 48 0.001 47 < 49 ) language [function] was associated with the left temporal lobe cortical md ( p < 0.001 , corrected for multiple comparisons ) , inferior longitudinal fasciculus , fornix , and posterior cingulum fa ( p < 0.05 ) . 0 ###LEFT-WALL### 1 language 0 ###LEFT-WALL### 4 associated 0 ###LEFT-WALL### 22 , 0 ###LEFT-WALL### 38 . 1 language 3 was 3 was 4 associated 4 associated 5 with 4 associated 14 < 4 associated 17 corrected 5 with 7 left 5 with 11 md 6 the 7 left 8 temporal 9 lobe 9 lobe 11 md 10 cortical 11 md 12 ( 14 < 13 p 14 < 14 < 15 0.001 16 , 17 corrected 17 corrected 18 for 17 corrected 21 ) 18 for 20 comparisons 19 multiple 20 comparisons 22 , 29 and 23 inferior 25 fasciculus 24 longitudinal 25 fasciculus 25 fasciculus 26 , 26 , 27 fornix 26 , 29 and 28 , 29 and 29 and 32 fa 29 and 35 < 30 posterior 31 cingulum 31 cingulum 32 fa 33 ( 35 < 34 p 35 < 35 < 36 0.05 35 < 37 ) attention and executive function [was] associated with the posterior and anterior cingulum fa , and visual - spatial function [was] associated with posterior cingulum fa ( p < 0.01 ) . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 31 . 1 attention 2 and 2 and 4 function 2 and 6 associated 3 executive 4 function 6 associated 7 with 7 with 9 posterior 8 the 9 posterior 10 and 15 and 10 and 21 associated 11 anterior 12 cingulum 12 cingulum 13 fa 13 fa 15 and 14 , 15 and 15 and 19 function 15 and 21 associated 16 visual 17 - 16 visual 19 function 18 spatial 19 function 21 associated 22 with 21 associated 25 fa 22 with 24 cingulum 23 posterior 24 cingulum 25 fa 28 < 26 ( 28 < 27 p 28 < 28 < 29 0.01 28 < 30 ) conclusion : specific cognitive domain functions are associated with distinct patterns of cortical and white matter diffusivity in elderly with no dementia . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 23 . 1 conclusion 2 : 2 : 3 specific 3 specific 6 functions 3 specific 18 in 3 specific 19 elderly 4 cognitive 5 domain 5 domain 6 functions 6 functions 7 are 7 are 8 associated 8 associated 9 with 8 associated 18 in 9 with 11 patterns 10 distinct 11 patterns 11 patterns 12 of 12 of 17 diffusivity 13 cortical 14 and 14 and 15 white 14 and 17 diffusivity 16 matter 17 diffusivity 19 elderly 20 with 20 with 22 dementia 21 no 22 dementia posterior cingulum tract fa was associated with all 4 cognitive domain functions , in agreement with the hypothesis that the posterior cingulate cortex is the main connectivity hub for cognitive brain networks . 0 ###LEFT-WALL### 4 fa 0 ###LEFT-WALL### 6 associated 1 posterior 2 cingulum 2 cingulum 4 fa 3 tract 4 fa 4 fa 5 was 5 was 6 associated 6 associated 7 with 7 with 12 functions 8 all 9 4 9 4 12 functions 10 cognitive 11 domain 11 domain 12 functions 12 functions 14 in 13 , 14 in 14 in 15 agreement 14 in 33 . 15 agreement 16 with 15 agreement 29 for 16 with 18 hypothesis 17 the 18 hypothesis 18 hypothesis 19 that 19 that 23 cortex 19 that 24 is 20 the 23 cortex 21 posterior 23 cortex 22 cingulate 23 cortex 23 cortex 24 is 24 is 28 hub 25 the 28 hub 26 main 28 hub 27 connectivity 28 hub 29 for 32 networks 30 cognitive 31 brain 31 brain 32 networks microstructural changes identified on dti may be associated with neurodegenerative pathologies underlying cognitive changes in older adults without dementia . 0 ###LEFT-WALL### 1 microstructural 0 ###LEFT-WALL### 8 associated 0 ###LEFT-WALL### 20 . 1 microstructural 2 changes 1 microstructural 3 identified 1 microstructural 6 may 2 changes 3 identified 3 identified 4 on 4 on 5 dti 6 may 7 be 7 be 8 associated 8 associated 9 with 8 associated 15 in 9 with 11 pathologies 10 neurodegenerative 11 pathologies 11 pathologies 12 underlying 12 underlying 14 changes 13 cognitive 14 changes 15 in 17 adults 16 older 17 adults 17 adults 18 without 18 without 19 dementia squamous cell carcinoma arises from highly proliferative basal layer epithelial cells , which normally divide for a short time before detaching from the basement membrane and undergoing terminal differentiation . 0 ###LEFT-WALL### 3 carcinoma 0 ###LEFT-WALL### 4 arises 0 ###LEFT-WALL### 12 , 0 ###LEFT-WALL### 30 . 1 squamous 3 carcinoma 2 cell 3 carcinoma 3 carcinoma 4 arises 4 arises 5 from 5 from 11 cells 6 highly 7 proliferative 7 proliferative 8 basal 8 basal 11 cells 9 layer 11 cells 10 epithelial 11 cells 12 , 13 which 12 , 15 divide 13 which 15 divide 14 normally 15 divide 15 divide 16 for 15 divide 19 time 15 divide 20 before 16 for 18 short 17 a 18 short 20 before 21 detaching 21 detaching 22 from 21 detaching 26 and 22 from 24 basement 23 the 24 basement 25 membrane 26 and 26 and 29 differentiation 27 undergoing 28 terminal 28 terminal 29 differentiation basal layer cells in stratified epithelia express the reverse transcriptase known as telomerase . 0 ###LEFT-WALL### 3 cells 0 ###LEFT-WALL### 7 express 0 ###LEFT-WALL### 14 . 1 basal 2 layer 2 layer 3 cells 3 cells 4 in 3 cells 7 express 4 in 6 epithelia 5 stratified 6 epithelia 7 express 10 transcriptase 8 the 10 transcriptase 9 reverse 10 transcriptase 10 transcriptase 11 known 11 known 12 as 12 as 13 telomerase most human cells do not express telomerase and therefore [are] subject to loss of telomeric dna with age due to the inability of lagging strand synthesis to completely replicate chromosomal ends . 0 ###LEFT-WALL### 3 cells 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 32 . 1 most 2 human 2 human 3 cells 3 cells 8 and 4 do 5 not 4 do 6 express 4 do 8 and 6 express 7 telomerase 8 and 11 subject 8 and 12 to 8 and 17 with 8 and 20 to 9 therefore 11 subject 12 to 13 loss 13 loss 14 of 14 of 16 dna 15 telomeric 16 dna 17 with 18 age 19 due 20 to 20 to 22 inability 21 the 22 inability 22 inability 23 of 22 inability 27 to 22 inability 29 replicate 23 of 26 synthesis 24 lagging 26 synthesis 25 strand 26 synthesis 27 to 29 replicate 28 completely 29 replicate 29 replicate 31 ends 30 chromosomal 31 ends late generation telomerase deficient mice exhibit signs of premature aging including reduced function [of] proliferating cellular compartments . 0 ###LEFT-WALL### 5 mice 0 ###LEFT-WALL### 6 exhibit 0 ###LEFT-WALL### 18 . 1 late 2 generation 2 generation 5 mice 3 telomerase 5 mice 4 deficient 5 mice 5 mice 6 exhibit 6 exhibit 7 signs 7 signs 8 of 8 of 17 compartments 9 premature 17 compartments 10 aging 17 compartments 11 including 12 reduced 12 reduced 17 compartments 13 function 15 proliferating 15 proliferating 17 compartments 16 cellular 17 compartments we examined development of squamous cell carcinoma in a telomerase deficient murine background with long and short telomeres . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 examined 0 ###LEFT-WALL### 19 . 1 we 2 examined 2 examined 3 development 2 examined 8 in 2 examined 14 with 3 development 4 of 4 of 7 carcinoma 5 squamous 6 cell 6 cell 7 carcinoma 8 in 13 background 9 a 13 background 10 telomerase 13 background 11 deficient 12 murine 12 murine 13 background 14 with 18 telomeres 15 long 16 and 16 and 17 short 16 and 18 telomeres g1 terc - [/] - mice ( long telomeres ) had fewer lymph node metastases , which correlated with increased numbers of apoptotic cells in these tumors compared with wild - type mice . 0 ###LEFT-WALL### 2 terc 0 ###LEFT-WALL### 3 - 1 g1 2 terc 3 - 5 - 3 - 11 had 3 - 16 , 3 - 34 . 5 - 6 mice 6 mice 9 telomeres 6 mice 11 had 7 ( 9 telomeres 8 long 9 telomeres 9 telomeres 10 ) 11 had 15 metastases 12 fewer 15 metastases 13 lymph 15 metastases 14 node 15 metastases 16 , 17 which 16 , 18 correlated 17 which 18 correlated 18 correlated 19 with 18 correlated 25 in 19 with 24 cells 20 increased 21 numbers 21 numbers 22 of 21 numbers 24 cells 22 of 24 cells 23 apoptotic 24 cells 25 in 27 tumors 26 these 27 tumors 27 tumors 28 compared 28 compared 29 with 29 with 33 mice 30 wild 31 - 30 wild 33 mice 32 type 33 mice however , g5 terc - [/] [-] mice with short telomeres had increased metastatic tumor burden similar to wild type mice . 0 ###LEFT-WALL### 8 mice 0 ###LEFT-WALL### 13 increased 0 ###LEFT-WALL### 22 . 1 however 2 , 1 however 8 mice 2 , 3 g5 3 g5 8 mice 4 terc 5 - 4 terc 8 mice 8 mice 9 with 8 mice 12 had 9 with 11 telomeres 10 short 11 telomeres 12 had 13 increased 13 increased 16 burden 14 metastatic 15 tumor 15 tumor 16 burden 16 burden 17 similar 17 similar 18 to 18 to 21 mice 19 wild 20 type 20 type 21 mice this increased metastasis correlated with genomic instability and aneuploidy in tumor cells from g5 terc - [/] - mice . 0 ###LEFT-WALL### 1 this 0 ###LEFT-WALL### 2 increased 0 ###LEFT-WALL### 18 - 1 this 2 increased 2 increased 3 metastasis 3 metastasis 4 correlated 4 correlated 5 with 5 with 8 and 6 genomic 7 instability 7 instability 8 and 8 and 9 aneuploidy 8 and 16 - 9 aneuploidy 10 in 10 in 12 cells 11 tumor 12 cells 12 cells 13 from 13 from 15 terc 14 g5 15 terc 18 - 19 mice 18 - 20 . a number of similarities with human scc were noted in the mouse model , and dramatic differences in global gene expression profiles were shown between primary and metastatic tumors . 0 ###LEFT-WALL### 4 similarities 0 ###LEFT-WALL### 9 noted 0 ###LEFT-WALL### 15 and 0 ###LEFT-WALL### 30 . 1 a 2 number 2 number 3 of 2 number 4 similarities 3 of 4 similarities 4 similarities 5 with 4 similarities 8 were 5 with 7 scc 6 human 7 scc 8 were 9 noted 9 noted 10 in 10 in 13 model 11 the 13 model 12 mouse 13 model 14 , 15 and 15 and 17 differences 15 and 24 shown 16 dramatic 17 differences 17 differences 18 in 17 differences 23 were 18 in 22 profiles 19 global 20 gene 20 gene 22 profiles 21 expression 22 profiles 23 were 24 shown 24 shown 25 between 25 between 29 tumors 26 primary 27 and 27 and 28 metastatic 27 and 29 tumors we concluded that telomere shortening promotes metastatic tumor development in a terc null mouse model of head and neck cancer . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 concluded 0 ###LEFT-WALL### 21 . 1 we 2 concluded 2 concluded 3 that 3 that 5 shortening 3 that 6 promotes 4 telomere 5 shortening 5 shortening 6 promotes 6 promotes 9 development 6 promotes 10 in 7 metastatic 8 tumor 8 tumor 9 development 10 in 18 and 11 a 15 model 12 terc 15 model 13 null 14 mouse 14 mouse 15 model 15 model 16 of 15 model 18 and 16 of 17 head 18 and 20 cancer 19 neck 20 cancer none background : reaching is a vital action requiring precise motor coordination [and] attempting to reach for objects that are too far away can destabilize balance and result in falls and injury . 0 ###LEFT-WALL### 1 none 0 ###LEFT-WALL### 5 is 0 ###LEFT-WALL### 33 . 1 none 2 background 1 none 4 reaching 1 none 5 is 2 background 3 : 3 : 4 reaching 5 is 31 and 6 a 8 action 7 vital 8 action 8 action 9 requiring 8 action 31 and 9 requiring 12 coordination 9 requiring 30 falls 10 precise 12 coordination 11 motor 12 coordination 12 coordination 14 attempting 12 coordination 27 and 12 coordination 30 falls 14 attempting 15 to 14 attempting 16 reach 14 attempting 24 can 15 to 16 reach 16 reach 17 for 17 for 18 objects 18 objects 19 that 18 objects 20 are 19 that 20 are 20 are 21 too 20 are 22 far 22 far 23 away 24 can 27 and 25 destabilize 26 balance 25 destabilize 27 and 27 and 28 result 27 and 29 in 28 result 29 in 31 and 32 injury this could be particularly important for many elderly people with age - related loss of sensorimotor function [and] [a] reduced ability to recover balance . 0 ###LEFT-WALL### 1 this 0 ###LEFT-WALL### 3 be 0 ###LEFT-WALL### 13 related 1 this 2 could 2 could 3 be 3 be 5 important 4 particularly 5 important 5 important 6 for 5 important 10 with 6 for 9 people 7 many 9 people 8 elderly 9 people 10 with 11 age 12 - 13 related 13 related 14 loss 13 related 25 . 14 loss 15 of 15 of 21 ability 16 sensorimotor 20 reduced 17 function 20 reduced 20 reduced 21 ability 21 ability 22 to 21 ability 23 recover 22 to 23 recover 23 recover 24 balance here , we investigate the interaction between reaching ability , errors in judging reach , and the incidence of falling [(] retrospectively and prospectively ) in a large cohort of older people . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 investigate 0 ###LEFT-WALL### 33 . 1 here 2 , 1 here 3 we 3 we 4 investigate 4 investigate 6 interaction 4 investigate 7 between 4 investigate 26 in 5 the 6 interaction 7 between 8 reaching 8 reaching 9 ability 9 ability 16 and 10 , 16 and 11 errors 12 in 11 errors 16 and 12 in 13 judging 13 judging 14 reach 15 , 16 and 16 and 18 incidence 16 and 19 of 16 and 25 ) 17 the 18 incidence 19 of 20 falling 20 falling 23 and 22 retrospectively 23 and 23 and 24 prospectively 26 in 29 cohort 27 a 28 large 27 a 29 cohort 28 large 29 cohort 29 cohort 30 of 30 of 32 people 31 older 32 people methods : participants ( n = 415 , 70 - 90 years ) had to estimate the furthest distance they could reach to retrieve a broomstick hanging in front of them . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 32 . 2 : 3 participants 2 : 14 had 3 participants 6 = 3 participants 10 - 3 participants 14 had 4 ( 6 = 5 n 6 = 6 = 7 415 8 , 10 - 9 70 10 - 10 - 12 years 10 - 13 ) 11 90 12 years 14 had 15 to 15 to 16 estimate 16 estimate 19 distance 16 estimate 23 to 17 the 18 furthest 17 the 19 distance 19 distance 20 they 19 distance 22 reach 20 they 21 could 21 could 22 reach 23 to 24 retrieve 24 retrieve 26 broomstick 25 a 26 broomstick 26 broomstick 27 hanging 26 broomstick 29 front 26 broomstick 30 of 28 in 29 front 30 of 31 them in an iterative [dialog] [with] [the] experimenter , the stick was moved until it was at the furthest distance they estimated to be reached successfully . 0 ###LEFT-WALL### 10 stick 0 ###LEFT-WALL### 12 moved 0 ###LEFT-WALL### 26 . 1 in 7 experimenter 1 in 8 , 1 in 10 stick 2 an 3 iterative 2 an 7 experimenter 3 iterative 7 experimenter 9 the 10 stick 10 stick 11 was 11 was 12 moved 12 moved 13 until 13 until 14 it 13 until 15 was 14 it 15 was 15 was 16 at 15 was 22 to 16 at 19 distance 17 the 18 furthest 17 the 19 distance 19 distance 20 they 19 distance 21 estimated 20 they 21 estimated 22 to 23 be 23 be 24 reached 24 reached 25 successfully at this point , participants were asked to attempt to retrieve the stick . 0 ###LEFT-WALL### 5 participants 0 ###LEFT-WALL### 7 asked 0 ###LEFT-WALL### 14 . 1 at 3 point 1 at 4 , 1 at 5 participants 2 this 3 point 5 participants 6 were 6 were 7 asked 7 asked 8 to 7 asked 9 attempt 8 to 9 attempt 9 attempt 10 to 9 attempt 11 retrieve 10 to 11 retrieve 11 retrieve 13 stick 12 the 13 stick actual maximal reach was then measured . 0 ###LEFT-WALL### 3 reach 0 ###LEFT-WALL### 4 was 0 ###LEFT-WALL### 7 . 1 actual 3 reach 2 maximal 3 reach 3 reach 4 was 4 was 5 then 4 was 6 measured the difference between attempted reach and actual maximal reach provided a measure of judgment error . 0 ###LEFT-WALL### 2 difference 0 ###LEFT-WALL### 10 provided 0 ###LEFT-WALL### 16 . 1 the 2 difference 2 difference 3 between 2 difference 10 provided 3 between 6 and 4 attempted 5 reach 5 reach 6 and 6 and 9 reach 7 actual 9 reach 8 maximal 9 reach 10 provided 15 error 11 a 12 measure 12 measure 13 of 12 measure 15 error 13 of 15 error 14 judgment 15 error one - year retrospective fall rates were obtained at initial assessment and [prospective] [falls] were monitored by monthly [calendar] . 0 ###LEFT-WALL### 1 one 0 ###LEFT-WALL### 2 - 0 ###LEFT-WALL### 20 . 2 - 6 rates 3 year 6 rates 4 retrospective 5 fall 5 fall 6 rates 6 rates 12 and 7 were 8 obtained 7 were 12 and 8 obtained 9 at 9 at 11 assessment 10 initial 11 assessment 12 and 15 were 12 and 17 by 12 and 18 monthly 15 were 16 monitored results : participants with poor maximal reach attempted shorter reaches than those who had good reaching ability . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 3 participants 2 : 8 attempted 2 : 18 . 3 participants 4 with 3 participants 8 attempted 4 with 7 reach 5 poor 7 reach 6 maximal 7 reach 8 attempted 10 reaches 8 attempted 11 than 9 shorter 10 reaches 11 than 12 those 12 those 13 who 12 those 14 had 13 who 14 had 14 had 17 ability 15 good 17 ability 16 reaching 17 ability those with the best reaching ability most accurately judged their maximal reach , whereas poor performers were dichotomous and either underestimated or overestimated their reach with few judging exactly . 0 ###LEFT-WALL### 1 those 0 ###LEFT-WALL### 9 judged 1 those 2 with 1 those 9 judged 2 with 4 best 3 the 4 best 4 best 5 reaching 5 reaching 6 ability 7 most 8 accurately 8 accurately 9 judged 9 judged 12 reach 9 judged 14 whereas 10 their 12 reach 11 maximal 12 reach 13 , 14 whereas 14 whereas 19 and 14 whereas 22 or 14 whereas 30 . 15 poor 16 performers 16 performers 17 were 16 performers 19 and 17 were 18 dichotomous 19 and 20 either 20 either 22 or 21 underestimated 22 or 22 or 23 overestimated 22 or 25 reach 24 their 25 reach 25 reach 26 with 26 with 27 few 27 few 28 judging 28 judging 29 exactly fall rates were significantly associated with reach [distance] but not with reach judgment error . 0 ###LEFT-WALL### 2 rates 0 ###LEFT-WALL### 5 associated 0 ###LEFT-WALL### 15 . 1 fall 2 rates 2 rates 3 were 3 were 4 significantly 3 were 5 associated 5 associated 9 but 6 with 7 reach 6 with 9 but 9 but 10 not 9 but 11 with 11 with 14 error 12 reach 14 error 13 judgment 14 error conclusions : maximal reach but not error in perceived reach is associated with falls in older people . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 4 reach 2 : 14 falls 2 : 18 . 3 maximal 4 reach 4 reach 5 but 4 reach 7 error 4 reach 13 with 4 reach 14 falls 5 but 6 not 7 error 8 in 7 error 11 is 8 in 10 reach 9 perceived 10 reach 11 is 12 associated 12 associated 13 with 14 falls 15 in 15 in 17 people 16 older 17 people background : aging in humans is characterized by a progressive loss of muscle [mass] and strength known as sarcopenia . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 3 aging 2 : 7 characterized 2 : 20 . 3 aging 4 in 3 aging 6 is 4 in 5 humans 6 is 7 characterized 7 characterized 8 by 7 characterized 18 as 8 by 11 loss 9 a 10 progressive 9 a 11 loss 10 progressive 11 loss 11 loss 12 of 12 of 15 and 13 muscle 15 and 15 and 16 strength 15 and 17 known 18 as 19 sarcopenia [although] considered to be a normal aspect of aging , the loss of strength can have significant effects on the health , functioning , and independence of elderly individuals . 0 ###LEFT-WALL### 12 loss 0 ###LEFT-WALL### 16 have 0 ###LEFT-WALL### 30 . 2 considered 3 to 2 considered 4 be 2 considered 10 , 2 considered 12 loss 3 to 4 be 4 be 7 aspect 5 a 6 normal 5 a 7 aspect 6 normal 7 aspect 7 aspect 8 of 8 of 9 aging 11 the 12 loss 12 loss 13 of 12 loss 15 can 13 of 14 strength 15 can 16 have 16 have 25 and 17 significant 18 effects 18 effects 19 on 18 effects 25 and 19 on 21 health 20 the 21 health 21 health 23 functioning 22 , 23 functioning 23 functioning 24 , 25 and 26 independence 25 and 27 of 27 of 29 individuals 28 elderly 29 individuals although these aspects of sarcopenia have been well studied , the molecular mechanisms leading to its development are still unclear . 0 ###LEFT-WALL### 13 mechanisms 0 ###LEFT-WALL### 18 are 0 ###LEFT-WALL### 21 . 1 although 3 aspects 1 although 7 been 1 although 10 , 1 although 13 mechanisms 2 these 3 aspects 3 aspects 4 of 3 aspects 6 have 4 of 5 sarcopenia 6 have 7 been 7 been 8 well 8 well 9 studied 11 the 13 mechanisms 12 molecular 13 mechanisms 13 mechanisms 14 leading 13 mechanisms 18 are 14 leading 15 to 15 to 17 development 16 its 17 development 18 are 19 still 18 are 20 unclear 19 still 20 unclear the nematode caenorhabditis elegans might be a novel animal model for sarcopenia as worms experience sarcopenia during aging and mutations affecting the daf - 2/insulin - like signaling [pathway] are able to delay this process . 0 ###LEFT-WALL### 4 elegans 0 ###LEFT-WALL### 6 be 0 ###LEFT-WALL### 19 and 0 ###LEFT-WALL### 33 delay 0 ###LEFT-WALL### 36 . 1 the 4 elegans 2 nematode 4 elegans 3 caenorhabditis 4 elegans 4 elegans 5 might 5 might 6 be 6 be 10 model 6 be 11 for 6 be 13 as 7 a 10 model 8 novel 10 model 9 animal 10 model 11 for 12 sarcopenia 13 as 15 experience 14 worms 15 experience 15 experience 16 sarcopenia 16 sarcopenia 17 during 17 during 18 aging 19 and 20 mutations 19 and 30 are 20 mutations 21 affecting 20 mutations 30 are 21 affecting 23 daf 21 affecting 27 like 22 the 23 daf 23 daf 25 2/insulin 24 - 25 2/insulin 25 2/insulin 26 - 27 like 28 signaling 30 are 31 able 31 able 32 to 32 to 33 delay 33 delay 35 process 34 this 35 process methods : via the use of rna interference , we screened a total of 43 genes , most of which have been shown to be required for the enhanced longevity of daf - 2 mutants , to assess for the effects of these genes on muscle function and worm mobility during aging . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 9 , 1 methods 2 : 2 : 3 via 3 via 5 use 4 the 5 use 5 use 6 of 6 of 8 interference 7 rna 8 interference 9 , 10 we 9 , 11 screened 9 , 33 - 10 we 11 screened 11 screened 13 total 12 a 13 total 13 total 14 of 14 of 16 genes 15 43 16 genes 16 genes 18 most 17 , 18 most 18 most 19 of 18 most 33 - 19 of 20 which 20 which 21 have 21 have 22 been 22 been 23 shown 23 shown 24 to 23 shown 27 for 24 to 25 be 25 be 26 required 27 for 30 longevity 28 the 30 longevity 29 enhanced 30 longevity 30 longevity 31 of 31 of 32 daf 33 - 35 mutants 34 2 35 mutants 35 mutants 37 to 36 , 37 to 37 to 48 and 37 to 53 . 38 assess 39 for 38 assess 44 genes 38 assess 47 function 38 assess 48 and 39 for 41 effects 40 the 41 effects 41 effects 42 of 42 of 43 these 44 genes 45 on 44 genes 47 function 45 on 46 muscle 48 and 49 worm 49 worm 50 mobility 50 mobility 51 during 51 during 52 aging results : we identified 17 novel genes that are essential for the delay in the onset of sarcopenia in daf - 2 mutants . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 3 we 2 : 4 identified 3 we 4 identified 4 identified 7 genes 4 identified 14 in 4 identified 19 in 5 17 7 genes 6 novel 7 genes 7 genes 8 that 7 genes 9 are 8 that 9 are 9 are 10 essential 10 essential 11 for 11 for 13 delay 12 the 13 delay 14 in 16 onset 15 the 16 onset 16 onset 17 of 17 of 18 sarcopenia 19 in 20 daf 20 daf 23 mutants 21 - 23 mutants 22 2 23 mutants 23 mutants 24 . the identified genes include splicing factors , vacuolar sorting proteins , transcription factors , and metabolic enzymes . 0 ###LEFT-WALL### 3 genes 0 ###LEFT-WALL### 4 include 0 ###LEFT-WALL### 7 , 0 ###LEFT-WALL### 18 . 1 the 3 genes 2 identified 3 genes 3 genes 4 include 4 include 6 factors 5 splicing 6 factors 7 , 15 and 8 vacuolar 9 sorting 8 vacuolar 11 , 9 sorting 10 proteins 11 , 13 factors 11 , 15 and 12 transcription 13 factors 14 , 15 and 15 and 17 enzymes 16 metabolic 17 enzymes using a transgenic strain that only responds to rna interference in the body wall muscle , we also found that most of the identified genes act in muscle to prevent the onset of sarcopenia . 0 ###LEFT-WALL### 17 we 0 ###LEFT-WALL### 30 prevent 0 ###LEFT-WALL### 35 . 1 using 4 strain 1 using 16 , 1 using 17 we 2 a 4 strain 3 transgenic 4 strain 4 strain 5 that 4 strain 7 responds 5 that 7 responds 6 only 7 responds 7 responds 8 to 7 responds 11 in 8 to 10 interference 9 rna 10 interference 11 in 15 muscle 12 the 15 muscle 13 body 14 wall 14 wall 15 muscle 17 we 19 found 18 also 19 found 19 found 20 that 20 that 25 genes 20 that 26 act 21 most 22 of 21 most 25 genes 22 of 25 genes 23 the 25 genes 24 identified 25 genes 25 genes 26 act 26 act 27 in 26 act 29 to 27 in 28 muscle 29 to 30 prevent 30 prevent 32 onset 31 the 32 onset 32 onset 33 of 33 of 34 sarcopenia conclusions : our results demonstrate that at least in worms , specific genetic pathways that modify the development of sarcopenia can be identified . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 24 . 2 : 4 results 2 : 5 demonstrate 3 our 4 results 4 results 5 demonstrate 5 demonstrate 6 that 6 that 8 least 6 that 14 pathways 6 that 23 identified 7 at 8 least 9 in 10 worms 9 in 11 , 9 in 14 pathways 12 specific 14 pathways 13 genetic 14 pathways 14 pathways 15 that 14 pathways 16 modify 14 pathways 21 can 15 that 16 modify 16 modify 18 development 17 the 18 development 18 development 19 of 19 of 20 sarcopenia 21 can 22 be 22 be 23 identified interestingly , almost all the identified genes also have a known human homolog , and hence , our findings may offer significant leads toward the identification of genes involved in sarcopenia in people . 0 ###LEFT-WALL### 4 all 0 ###LEFT-WALL### 9 have 0 ###LEFT-WALL### 15 and 0 ###LEFT-WALL### 34 . 1 interestingly 2 , 1 interestingly 4 all 3 almost 4 all 4 all 5 the 4 all 7 genes 4 all 9 have 5 the 7 genes 6 identified 7 genes 8 also 9 have 9 have 13 homolog 10 a 13 homolog 11 known 13 homolog 12 human 13 homolog 14 , 15 and 15 and 19 findings 15 and 21 offer 16 hence 17 , 16 hence 19 findings 18 our 19 findings 19 findings 20 may 20 may 21 offer 21 offer 23 leads 21 offer 24 toward 22 significant 23 leads 24 toward 26 identification 25 the 26 identification 26 identification 27 of 27 of 28 genes 28 genes 29 involved 29 involved 30 in 29 involved 32 in 30 in 31 sarcopenia 32 in 33 people background : evidence suggests that gait is influenced by higher order cognitive and cortical control mechanisms . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 3 evidence 2 : 4 suggests 2 : 17 . 3 evidence 4 suggests 4 suggests 6 gait 4 suggests 8 influenced 5 that 6 gait 6 gait 7 is 7 is 8 influenced 8 influenced 9 by 9 by 16 mechanisms 10 higher 11 order 11 order 16 mechanisms 12 cognitive 13 and 13 and 14 cortical 13 and 15 control 15 control 16 mechanisms however , less is known about the functional [correlates] [of] cortical control [of] gait . 0 ###LEFT-WALL### 3 less 0 ###LEFT-WALL### 5 known 0 ###LEFT-WALL### 15 . 1 however 2 , 1 however 3 less 3 less 4 is 4 is 5 known 5 known 6 about 6 about 14 gait 7 the 14 gait 8 functional 12 control 11 cortical 12 control 12 control 14 gait methods : using functional near - infrared spectroscopy , the current study was designed to evaluate whether increased activations in the prefrontal cortex ( pfc ) were detected in walking while talking ( wwt ) compared with normal pace [walking] [(] nw ) in 11 young and 11 old participants . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 51 . 1 methods 2 : 2 : 3 using 3 using 8 spectroscopy 3 using 44 in 4 functional 8 spectroscopy 5 near 6 - 5 near 8 spectroscopy 7 infrared 8 spectroscopy 8 spectroscopy 11 current 9 , 11 current 10 the 11 current 11 current 12 study 11 current 16 evaluate 11 current 43 ) 12 study 13 was 13 was 14 designed 14 designed 15 to 14 designed 16 evaluate 15 to 16 evaluate 16 evaluate 17 whether 17 whether 19 activations 17 whether 28 detected 18 increased 19 activations 19 activations 20 in 19 activations 25 pfc 19 activations 27 were 20 in 23 cortex 21 the 23 cortex 22 prefrontal 23 cortex 24 ( 25 pfc 25 pfc 26 ) 27 were 28 detected 28 detected 29 in 29 in 30 walking 30 walking 31 while 30 walking 37 with 31 while 32 talking 31 while 36 compared 32 talking 34 wwt 32 talking 36 compared 33 ( 34 wwt 34 wwt 35 ) 37 with 42 nw 38 normal 39 pace 39 pace 42 nw 44 in 50 participants 45 11 50 participants 46 young 47 and 47 and 49 old 47 and 50 participants 48 11 49 old specifically , the following two hypotheses were evaluated : [(] a [ )(activation in the pfc would be increased in wwt compared with nw [.] [(] [b] [ )(the increase in activation in the pfc during wwt as compared [with] nw would be greater in young than in old participants [.] 0 ###LEFT-WALL### 6 hypotheses 0 ###LEFT-WALL### 9 : 1 specifically 2 , 1 specifically 6 hypotheses 3 the 4 following 3 the 5 two 5 two 6 hypotheses 6 hypotheses 7 were 7 were 8 evaluated 9 : 13 )(activation 9 : 19 increased 11 a 13 )(activation 13 )(activation 14 in 13 )(activation 17 would 14 in 16 pfc 15 the 16 pfc 17 would 18 be 18 be 19 increased 19 increased 20 in 19 increased 31 in 20 in 21 wwt 21 wwt 22 compared 22 compared 23 with 23 with 24 nw 23 with 30 increase 29 )(the 30 increase 31 in 32 activation 32 activation 33 in 33 in 35 pfc 34 the 35 pfc 35 pfc 36 during 35 pfc 46 young 36 during 37 wwt 37 wwt 41 nw 37 wwt 45 in 38 as 39 compared 39 compared 41 nw 41 nw 42 would 42 would 43 be 43 be 44 greater 44 greater 45 in 46 young 47 than 46 young 48 in 48 in 50 participants 49 old 50 participants furthermore , the group [-] by [-] task interaction was significant in 11 channels with young participants showing greater wwt - related increase [in] hbo2 levels compared with the old participants . 0 ###LEFT-WALL### 4 group 0 ###LEFT-WALL### 10 was 0 ###LEFT-WALL### 22 related 1 furthermore 2 , 1 furthermore 4 group 3 the 4 group 4 group 6 by 4 group 10 was 6 by 9 interaction 8 task 9 interaction 10 was 11 significant 11 significant 12 in 12 in 14 channels 13 11 14 channels 14 channels 15 with 14 channels 18 showing 15 with 17 participants 16 young 17 participants 18 showing 20 wwt 19 greater 20 wwt 21 - 22 related 22 related 26 levels 22 related 28 with 22 related 32 . 23 increase 26 levels 25 hbo2 26 levels 26 levels 27 compared 28 with 31 participants 29 the 31 participants 30 old 31 participants conclusions : this study provided the first evidence that oxygenation levels are increased in the pfc during wwt compared with nw in young and old individuals . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 27 . 1 conclusions 2 : 2 : 4 study 3 this 4 study 4 study 5 provided 4 study 8 evidence 4 study 13 increased 6 the 7 first 6 the 8 evidence 8 evidence 9 that 8 evidence 12 are 8 evidence 13 increased 9 that 11 levels 9 that 12 are 10 oxygenation 11 levels 11 levels 12 are 13 increased 14 in 13 increased 20 with 14 in 16 pfc 15 the 16 pfc 16 pfc 17 during 16 pfc 19 compared 17 during 18 wwt 20 with 21 nw 20 with 22 in 22 in 26 individuals 23 young 24 and 24 and 25 old 24 and 26 individuals this effect was modified by age suggesting that older adults may [under] - utilize the pfc in attention - demanding locomotion tasks . 0 ###LEFT-WALL### 2 effect 0 ###LEFT-WALL### 4 modified 0 ###LEFT-WALL### 13 - 0 ###LEFT-WALL### 23 . 1 this 2 effect 2 effect 3 was 3 was 4 modified 4 modified 5 by 5 by 6 age 6 age 7 suggesting 7 suggesting 8 that 8 that 10 adults 8 that 11 may 9 older 10 adults 10 adults 11 may 13 - 14 utilize 13 - 19 - 14 utilize 16 pfc 14 utilize 17 in 15 the 16 pfc 17 in 18 attention 19 - 21 locomotion 19 - 22 tasks 20 demanding 21 locomotion 21 locomotion 22 tasks purpose : with the rapid growth in the older inmate population and the economic impact [of] end - of [-] life treatments within the cash - strapped prison system , consideration should be given to inmate treatment preferences . 0 ###LEFT-WALL### 1 purpose 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 26 - 1 purpose 2 : 2 : 3 with 2 : 7 in 3 with 6 growth 4 the 6 growth 5 rapid 6 growth 7 in 12 and 8 the 11 population 9 older 10 inmate 10 inmate 11 population 11 population 12 and 12 and 17 end 12 and 19 of 13 the 17 end 14 economic 15 impact 15 impact 17 end 18 - 19 of 19 of 22 treatments 19 of 26 - 21 life 22 treatments 22 treatments 23 within 23 within 25 cash 24 the 25 cash 26 - 29 system 26 - 30 , 26 - 39 . 27 strapped 29 system 28 prison 29 system 30 , 31 consideration 30 , 34 given 31 consideration 32 should 32 should 33 be 33 be 34 given 34 given 35 to 35 to 38 preferences 36 inmate 38 preferences 37 treatment 38 preferences we [examined] end - [of] - life treatment preferences and days of desired life for several health scenarios among male inmates incarcerated primarily for murder . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 end 0 ###LEFT-WALL### 4 - 1 we 3 end 4 - 6 - 4 - 22 incarcerated 4 - 26 . 6 - 10 and 7 life 9 preferences 8 treatment 9 preferences 9 preferences 10 and 10 and 11 days 10 and 12 of 12 of 14 life 13 desired 14 life 14 life 15 for 15 for 16 several 16 several 18 scenarios 16 several 22 incarcerated 17 health 18 scenarios 18 scenarios 19 among 18 scenarios 22 incarcerated 19 among 21 inmates 20 male 21 inmates 22 incarcerated 23 primarily 23 primarily 24 for 24 for 25 murder design and methods : inmates over the age of 45 who passed a cognitive screening completed face - to [-] face interviews ( n = 94 ; mean age = 57.7 ; sd = 10.68 [ )( 0 ###LEFT-WALL### 3 methods 0 ###LEFT-WALL### 4 : 0 ###LEFT-WALL### 27 ; 0 ###LEFT-WALL### 37 )( 1 design 2 and 2 and 3 methods 3 methods 4 : 4 : 5 inmates 5 inmates 6 over 5 inmates 9 of 6 over 8 age 7 the 8 age 9 of 10 45 10 45 11 who 10 45 12 passed 10 45 19 to 11 who 12 passed 12 passed 17 face 13 a 17 face 14 cognitive 17 face 15 screening 16 completed 16 completed 17 face 18 - 19 to 19 to 21 face 19 to 27 ; 21 face 22 interviews 22 interviews 25 = 23 ( 25 = 24 n 25 = 25 = 26 94 25 = 27 ; 27 ; 29 age 27 ; 30 = 27 ; 32 ; 28 mean 29 age 29 age 30 = 30 = 31 57.7 32 ; 33 sd 32 ; 34 = 33 sd 34 = 34 = 35 10.68 results : we found a 3 [-] way interaction indicating that the effect of parole expectation on desire for life [-] sustaining treatment varied by race/ethnicity and treatment . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 3 we 2 : 4 found 2 : 29 . 3 we 4 found 4 found 9 interaction 4 found 13 effect 4 found 17 on 5 a 9 interaction 6 3 9 interaction 8 way 9 interaction 9 interaction 10 indicating 10 indicating 11 that 12 the 13 effect 13 effect 14 of 14 of 16 expectation 15 parole 16 expectation 17 on 27 and 18 desire 19 for 18 desire 22 sustaining 18 desire 27 and 19 for 20 life 22 sustaining 23 treatment 23 treatment 24 varied 24 varied 25 by 25 by 26 race/ethnicity 27 and 28 treatment minority inmates desired cardiopulmonary resuscitation or feeding tubes only if they believed that they would be paroled . 0 ###LEFT-WALL### 2 inmates 0 ###LEFT-WALL### 4 cardiopulmonary 0 ###LEFT-WALL### 6 or 0 ###LEFT-WALL### 18 . 1 minority 2 inmates 2 inmates 3 desired 2 inmates 4 cardiopulmonary 4 cardiopulmonary 5 resuscitation 6 or 7 feeding 6 or 17 paroled 7 feeding 8 tubes 7 feeding 10 if 7 feeding 16 be 9 only 10 if 10 if 11 they 10 if 12 believed 11 they 12 believed 12 believed 13 that 13 that 14 they 13 that 15 would 14 they 15 would 16 be 17 paroled the model predicting desire for palliative care was not significant . 0 ###LEFT-WALL### 4 desire 0 ###LEFT-WALL### 8 was 0 ###LEFT-WALL### 11 . 1 the 4 desire 2 model 4 desire 3 predicting 4 desire 4 desire 5 for 4 desire 8 was 5 for 7 care 6 palliative 7 care 8 was 9 not 8 was 10 significant future days of desired life were related to prospective health condition , fear of death , negative [affect] , and trust in prison health care . 0 ###LEFT-WALL### 2 days 0 ###LEFT-WALL### 20 and 0 ###LEFT-WALL### 26 . 1 future 2 days 2 days 3 of 2 days 20 and 3 of 5 life 4 desired 5 life 6 were 7 related 6 were 20 and 7 related 8 to 7 related 17 negative 8 to 11 condition 9 prospective 11 condition 10 health 11 condition 11 condition 13 fear 12 , 13 fear 13 fear 14 of 13 fear 16 , 14 of 15 death 19 , 20 and 20 and 21 trust 20 and 22 in 22 in 25 care 23 prison 25 care 24 health 25 care caucasian inmates expressed a desire for more days of life out of prison , whereas minority inmates did not differ in days of desired life either [in] or out of prison . 0 ###LEFT-WALL### 28 or 0 ###LEFT-WALL### 32 . 1 caucasian 28 or 2 inmates 3 expressed 3 expressed 5 desire 3 expressed 12 of 3 expressed 15 whereas 3 expressed 26 either 4 a 5 desire 5 desire 6 for 5 desire 9 of 6 for 8 days 7 more 8 days 9 of 10 life 11 out 12 of 12 of 13 prison 14 , 15 whereas 15 whereas 17 inmates 15 whereas 20 differ 15 whereas 26 either 16 minority 17 inmates 17 inmates 18 did 18 did 19 not 18 did 20 differ 20 differ 21 in 21 in 22 days 22 days 23 of 23 of 25 life 24 desired 25 life 26 either 28 or 28 or 29 out 28 or 30 of 30 of 31 prison minorities wanted more days of life than caucasians but only if they believed that they would be paroled . 0 ###LEFT-WALL### 1 minorities 0 ###LEFT-WALL### 2 wanted 0 ###LEFT-WALL### 7 than 0 ###LEFT-WALL### 19 . 1 minorities 2 wanted 2 wanted 3 more 2 wanted 4 days 4 days 5 of 5 of 6 life 7 than 15 they 7 than 18 paroled 8 caucasians 15 they 9 but 10 only 9 but 15 they 11 if 12 they 11 if 13 believed 11 if 15 they 12 they 13 believed 13 believed 14 that 15 they 16 would 16 would 17 be 17 be 18 paroled implications : end - of [-] life care for the burgeoning inmate population is costly , and active life - sustaining treatments may not be desired under certain conditions . 0 ###LEFT-WALL### 1 implications 0 ###LEFT-WALL### 3 end 0 ###LEFT-WALL### 4 - 0 ###LEFT-WALL### 30 . 1 implications 2 : 2 : 3 end 4 - 13 population 4 - 14 is 4 - 20 - 5 of 8 care 5 of 13 population 7 life 8 care 8 care 9 for 9 for 11 burgeoning 10 the 11 burgeoning 12 inmate 13 population 13 population 14 is 14 is 19 life 15 costly 17 and 16 , 17 and 17 and 18 active 17 and 19 life 20 - 22 treatments 20 - 26 desired 21 sustaining 22 treatments 22 treatments 23 may 23 may 24 not 23 may 25 be 25 be 26 desired 26 desired 27 under 27 under 29 conditions 28 certain 29 conditions specifically , expectation of parole but not current functional ability interacts with future illness condition in explaining inmates ' desire for active treatment or days of desired life in the future . 0 ###LEFT-WALL### 3 expectation 0 ###LEFT-WALL### 11 interacts 0 ###LEFT-WALL### 32 . 1 specifically 2 , 1 specifically 3 expectation 3 expectation 4 of 3 expectation 6 but 3 expectation 11 interacts 4 of 5 parole 6 but 7 not 6 but 10 ability 8 current 10 ability 9 functional 10 ability 11 interacts 12 with 11 interacts 16 in 12 with 15 condition 13 future 14 illness 14 illness 15 condition 16 in 17 explaining 17 explaining 20 desire 18 inmates 19 ' 19 ' 20 desire 20 desire 21 for 20 desire 26 of 21 for 24 or 22 active 23 treatment 23 treatment 24 or 24 or 25 days 26 of 28 life 27 desired 28 life 28 life 29 in 29 in 31 future 30 the 31 future background : cd28 [(] [-] ) [t] lymphocytes progressively increase during aging , autoimmunity , and hiv - 1 infection . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 21 . 2 : 8 lymphocytes 2 : 10 increase 3 cd28 6 ) 3 cd28 8 lymphocytes 8 lymphocytes 10 increase 9 progressively 10 increase 10 increase 11 during 10 increase 20 infection 11 during 16 and 12 aging 13 , 13 , 14 autoimmunity 13 , 16 and 15 , 16 and 16 and 17 hiv 18 - 19 1 19 1 20 infection expansion of these cells stands in contrast with their senescent phenotype described by several studies . 0 ###LEFT-WALL### 1 expansion 0 ###LEFT-WALL### 5 stands 0 ###LEFT-WALL### 16 . 1 expansion 2 of 1 expansion 5 stands 2 of 4 cells 3 these 4 cells 5 stands 6 in 5 stands 8 with 6 in 7 contrast 8 with 11 phenotype 9 their 11 phenotype 10 senescent 11 phenotype 11 phenotype 12 described 12 described 13 by 13 by 15 studies 14 several 15 studies understanding the functional properties and phenotype of cd28 [(] [-] [ )(t cell during hiv - 1 infection is important , because this subset incorporates [t] cells specific for hiv - 1 [and] other chronic pathogens . 0 ###LEFT-WALL### 18 infection 0 ###LEFT-WALL### 19 is 0 ###LEFT-WALL### 31 - 1 understanding 13 cell 1 understanding 14 during 1 understanding 16 - 1 understanding 18 infection 2 the 13 cell 3 functional 4 properties 4 properties 5 and 5 and 6 phenotype 5 and 7 of 5 and 13 cell 7 of 8 cd28 8 cd28 12 )(t 14 during 15 hiv 17 1 18 infection 18 infection 19 is 19 is 20 important 20 important 22 because 21 , 22 because 22 because 24 subset 22 because 25 incorporates 22 because 31 - 23 this 24 subset 24 subset 25 incorporates 25 incorporates 27 cells 27 cells 28 specific 28 specific 29 for 29 for 30 hiv 31 - 36 pathogens 31 - 37 . 32 1 34 other 34 other 36 pathogens 35 chronic 36 pathogens methods : blood samples were obtained from 23 healthy and 43 hiv - 1 - infected individuals : 26 receiving antiretroviral therapy and 17 naive [to] treatment . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 28 . 2 : 4 samples 2 : 6 obtained 2 : 10 and 2 : 18 : 3 blood 4 samples 4 samples 5 were 5 were 6 obtained 6 obtained 7 from 6 obtained 9 healthy 7 from 8 23 10 and 12 hiv 10 and 16 infected 11 43 12 hiv 12 hiv 14 1 12 hiv 16 infected 13 - 14 1 14 1 15 - 16 infected 17 individuals 18 : 23 and 19 26 20 receiving 20 receiving 22 therapy 21 antiretroviral 22 therapy 22 therapy 23 and 23 and 27 treatment 24 17 27 treatment 25 naive 27 treatment the phenotype of cd28 [(] - [ )(and cd28 [(] [+] [ )(t cells was determined by flow cytometry . 0 ###LEFT-WALL### 2 phenotype 0 ###LEFT-WALL### 15 was 0 ###LEFT-WALL### 20 . 1 the 2 phenotype 2 phenotype 3 of 2 phenotype 15 was 3 of 8 )(and 4 cd28 8 )(and 6 - 8 )(and 8 )(and 14 cells 9 cd28 13 )(t 9 cd28 14 cells 15 was 16 determined 16 determined 17 by 17 by 19 cytometry 18 flow 19 cytometry [t] cells were activated through t - cell receptor [before] apoptosis and proliferation measurements . 0 ###LEFT-WALL### 2 cells 0 ###LEFT-WALL### 4 activated 0 ###LEFT-WALL### 7 - 2 cells 3 were 3 were 4 activated 4 activated 5 through 5 through 6 t 7 - 12 and 7 - 15 . 8 cell 11 apoptosis 9 receptor 11 apoptosis 11 apoptosis 12 and 12 and 14 measurements 13 proliferation 14 measurements interleukin ( il ) - 2 , tumor - necrosis factor , interferon [-] [γ] , and perforin production were analyzed using enzyme - linked immunosorbent assay . 0 ###LEFT-WALL### 8 tumor 0 ###LEFT-WALL### 9 - 1 interleukin 3 il 1 interleukin 6 2 1 interleukin 8 tumor 2 ( 3 il 3 il 4 ) 5 - 6 2 6 2 7 , 9 - 11 factor 9 - 12 , 9 - 24 - 10 necrosis 11 factor 12 , 13 interferon 12 , 17 and 16 , 17 and 17 and 19 production 17 and 21 analyzed 18 perforin 19 production 19 production 20 were 20 were 21 analyzed 21 analyzed 22 using 22 using 23 enzyme 24 - 27 assay 24 - 28 . 25 linked 27 assay 26 immunosorbent 27 assay results : cd28 [(] - [ )( cells from patients receiving antiretroviral therapy exhibited a low sensitivity to apoptosis and enhanced proliferation after tcr stimulation , compared with t cells of uninfected individuals . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 5 - 0 ###LEFT-WALL### 34 . 1 results 2 : 2 : 3 cd28 5 - 8 cells 5 - 26 , 8 cells 9 from 8 cells 11 receiving 8 cells 26 , 9 from 10 patients 11 receiving 13 therapy 12 antiretroviral 13 therapy 14 exhibited 17 sensitivity 14 exhibited 18 to 14 exhibited 26 , 15 a 16 low 15 a 17 sensitivity 16 low 17 sensitivity 18 to 20 and 19 apoptosis 20 and 20 and 22 proliferation 20 and 23 after 21 enhanced 22 proliferation 23 after 25 stimulation 24 tcr 25 stimulation 26 , 27 compared 27 compared 28 with 27 compared 30 cells 28 with 29 t 30 cells 31 of 31 of 33 individuals 32 uninfected 33 individuals on the contrary , cd28 [(] - ) [t] cells from viremic patients showed a decreased bcl - 2 expression , a high sensitivity to apoptosis , and poor proliferative ability , compared with treated patients and control subjects . 0 ###LEFT-WALL### 10 cells 0 ###LEFT-WALL### 14 showed 0 ###LEFT-WALL### 32 , 0 ###LEFT-WALL### 40 . 1 on 3 contrary 1 on 8 ) 1 on 10 cells 2 the 3 contrary 3 contrary 5 cd28 4 , 5 cd28 5 cd28 7 - 10 cells 11 from 10 cells 14 showed 11 from 13 patients 12 viremic 13 patients 14 showed 17 bcl 14 showed 24 sensitivity 14 showed 25 to 15 a 17 bcl 16 decreased 17 bcl 17 bcl 20 expression 18 - 20 expression 19 2 20 expression 20 expression 21 , 22 a 24 sensitivity 23 high 24 sensitivity 25 to 28 and 26 apoptosis 28 and 27 , 28 and 28 and 31 ability 29 poor 31 ability 30 proliferative 31 ability 32 , 37 and 33 compared 34 with 33 compared 37 and 34 with 36 patients 35 treated 36 patients 37 and 38 control 38 control 39 subjects [t] cells from untreated patients produced less il - 2 , possibly underlying their decreased proliferative abilities . 0 ###LEFT-WALL### 2 cells 0 ###LEFT-WALL### 6 produced 2 cells 3 from 2 cells 6 produced 3 from 5 patients 4 untreated 5 patients 6 produced 8 il 7 less 8 il 8 il 10 2 8 il 13 underlying 9 - 10 2 10 2 11 , 11 , 13 underlying 12 possibly 13 underlying 13 underlying 17 abilities 13 underlying 18 . 14 their 17 abilities 15 decreased 17 abilities 16 proliferative 17 abilities conclusions : the level of hiv - 1 replication and associated immunoactivation represent a critical factor in regulating survival and activation of cd28 [(] - [ )(t [cells] . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 20 and 2 : 25 - 2 : 29 . 3 the 4 level 4 level 5 of 4 level 20 and 5 of 6 hiv 6 hiv 10 and 6 hiv 13 represent 7 - 8 1 8 1 9 replication 9 replication 10 and 10 and 12 immunoactivation 10 and 13 represent 11 associated 12 immunoactivation 13 represent 16 factor 13 represent 17 in 14 a 15 critical 14 a 16 factor 15 critical 16 factor 17 in 18 regulating 18 regulating 19 survival 20 and 21 activation 20 and 22 of 22 of 23 cd28 25 - 27 )(t objective : the neurodevelopmental - neurodegenerative debate is a basic issue in the field of the neuropathological basis of schizophrenia ( sch ) . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 24 . 2 : 7 debate 2 : 8 is 3 the 7 debate 4 neurodevelopmental 5 - 4 neurodevelopmental 7 debate 6 neurodegenerative 7 debate 7 debate 8 is 8 is 11 issue 9 a 11 issue 10 basic 11 issue 11 issue 12 in 11 issue 15 of 12 in 14 field 13 the 14 field 15 of 18 basis 16 the 18 basis 17 neuropathological 18 basis 18 basis 19 of 18 basis 22 sch 19 of 20 schizophrenia 21 ( 22 sch 22 sch 23 ) neurophysiological techniques have been scarcely involved in such debate , but nonlinear analysis methods may contribute to it . 0 ###LEFT-WALL### 2 techniques 0 ###LEFT-WALL### 11 but 0 ###LEFT-WALL### 19 . 1 neurophysiological 2 techniques 2 techniques 11 but 3 have 4 been 3 have 11 but 4 been 6 involved 5 scarcely 6 involved 6 involved 7 in 7 in 9 debate 8 such 9 debate 10 , 11 but 11 but 16 contribute 12 nonlinear 13 analysis 13 analysis 14 methods 14 methods 15 may 15 may 16 contribute 16 contribute 17 to 17 to 18 it results : regression analyses indicated that lzc values were strongly dependent on age . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 4 analyses 2 : 9 were 2 : 14 . 3 regression 4 analyses 4 analyses 5 indicated 4 analyses 6 that 4 analyses 8 values 4 analyses 9 were 6 that 7 lzc 6 that 8 values 7 lzc 8 values 9 were 10 strongly 9 were 11 dependent 11 dependent 12 on 12 on 13 age complexity scores increased as a function of age in controls , while sch patients exhibited a progressive reduction of lzc values . 0 ###LEFT-WALL### 2 scores 0 ###LEFT-WALL### 3 increased 0 ###LEFT-WALL### 11 , 0 ###LEFT-WALL### 22 . 1 complexity 2 scores 2 scores 3 increased 3 increased 4 as 4 as 6 function 5 a 6 function 6 function 7 of 6 function 9 in 7 of 8 age 9 in 10 controls 11 , 14 patients 11 , 15 exhibited 12 while 13 sch 12 while 14 patients 14 patients 15 exhibited 15 exhibited 18 reduction 16 a 17 progressive 16 a 18 reduction 17 progressive 18 reduction 18 reduction 19 of 19 of 21 values 20 lzc 21 values a logistic model including lzc scores , age and the interaction of both variables allowed the classification of patients and controls with high sensitivity and specificity . 0 ###LEFT-WALL### 3 model 0 ###LEFT-WALL### 6 scores 0 ###LEFT-WALL### 7 , 0 ###LEFT-WALL### 27 . 1 a 3 model 2 logistic 3 model 3 model 4 including 3 model 6 scores 4 including 5 lzc 7 , 9 and 8 age 9 and 9 and 11 interaction 9 and 12 of 9 and 20 and 10 the 11 interaction 12 of 14 variables 13 both 14 variables 15 allowed 17 classification 15 allowed 20 and 16 the 17 classification 17 classification 18 of 18 of 19 patients 20 and 21 controls 20 and 22 with 22 with 25 and 23 high 24 sensitivity 24 sensitivity 25 and 25 and 26 specificity conclusions : results demonstrated that sch patients failed to follow the " normal " process of complexity increase as a function of age . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 24 . 1 conclusions 2 : 2 : 3 results 3 results 4 demonstrated 3 results 5 that 3 results 18 increase 5 that 7 patients 5 that 18 increase 6 sch 7 patients 7 patients 8 failed 7 patients 16 of 7 patients 18 increase 8 failed 9 to 9 to 10 follow 10 follow 15 process 11 the 12 " 11 the 15 process 13 normal 14 " 13 normal 15 process 16 of 17 complexity 18 increase 19 as 19 as 21 function 20 a 21 function 21 function 22 of 22 of 23 age in addition , sch patients exhibited a significant reduction of complexity scores as a function of age , thus paralleling the pattern observed in neurodegenerative diseases . 0 ###LEFT-WALL### 4 sch 0 ###LEFT-WALL### 12 scores 0 ###LEFT-WALL### 23 observed 1 in 2 addition 1 in 3 , 1 in 4 sch 4 sch 5 patients 4 sch 6 exhibited 4 sch 12 scores 5 patients 6 exhibited 6 exhibited 9 reduction 7 a 8 significant 7 a 9 reduction 8 significant 9 reduction 9 reduction 10 of 10 of 11 complexity 12 scores 13 as 13 as 15 function 14 a 15 function 15 function 16 of 16 of 17 age 18 , 23 observed 19 thus 20 paralleling 20 paralleling 22 pattern 20 paralleling 23 observed 21 the 22 pattern 23 observed 24 in 23 observed 27 . 24 in 26 diseases 25 neurodegenerative 26 diseases significance : our results support the notion of a progressive defect in sch , which does not contradict the existence of a basic neurodevelopmental alteration . 0 ###LEFT-WALL### 1 significance 0 ###LEFT-WALL### 2 : 2 : 4 results 2 : 5 support 2 : 14 , 2 : 26 . 3 our 4 results 4 results 5 support 5 support 7 notion 5 support 12 in 6 the 7 notion 7 notion 8 of 8 of 11 defect 9 a 10 progressive 9 a 11 defect 10 progressive 11 defect 12 in 13 sch 14 , 15 which 14 , 18 contradict 15 which 16 does 16 does 17 not 16 does 18 contradict 18 contradict 20 existence 19 the 20 existence 20 existence 21 of 21 of 25 alteration 22 a 23 basic 22 a 25 alteration 23 basic 25 alteration 24 neurodevelopmental 25 alteration lighter cells from density fractionated erythrocytes of sickle cell disease ( scd ) patients carry higher amount of externalized phosphatidylserine ( ps ) and cell surface glycophorins compared to the denser counterparts . 0 ###LEFT-WALL### 2 cells 0 ###LEFT-WALL### 5 fractionated 0 ###LEFT-WALL### 33 . 1 lighter 2 cells 2 cells 3 from 2 cells 5 fractionated 3 from 4 density 5 fractionated 6 erythrocytes 5 fractionated 29 to 6 erythrocytes 7 of 6 erythrocytes 14 patients 6 erythrocytes 15 carry 7 of 10 disease 8 sickle 10 disease 9 cell 10 disease 10 disease 12 scd 11 ( 12 scd 12 scd 13 ) 14 patients 15 carry 15 carry 24 and 16 higher 17 amount 17 amount 18 of 17 amount 24 and 18 of 20 phosphatidylserine 19 externalized 20 phosphatidylserine 20 phosphatidylserine 22 ps 21 ( 22 ps 22 ps 23 ) 24 and 27 glycophorins 24 and 28 compared 25 cell 27 glycophorins 26 surface 27 glycophorins 29 to 32 counterparts 30 the 32 counterparts 31 denser 32 counterparts further analysis also revealed that the denser cells contained higher levels of fetal hemoglobin ( hbf ) compared to the lighter cells , supported by the presence of larger number [of] f - cells in these populations . 0 ###LEFT-WALL### 2 analysis 0 ###LEFT-WALL### 18 compared 0 ###LEFT-WALL### 38 . 1 further 2 analysis 2 analysis 4 revealed 2 analysis 5 that 2 analysis 9 contained 2 analysis 18 compared 3 also 4 revealed 5 that 8 cells 5 that 9 contained 6 the 8 cells 7 denser 8 cells 8 cells 9 contained 9 contained 11 levels 10 higher 11 levels 11 levels 12 of 12 of 14 hemoglobin 13 fetal 14 hemoglobin 14 hemoglobin 16 hbf 15 ( 16 hbf 16 hbf 17 ) 18 compared 19 to 18 compared 34 cells 18 compared 35 in 19 to 22 cells 20 the 22 cells 21 lighter 22 cells 22 cells 24 supported 23 , 24 supported 24 supported 25 by 24 supported 33 - 25 by 27 presence 26 the 27 presence 27 presence 28 of 28 of 30 number 29 larger 30 number 30 number 32 f 35 in 37 populations 36 these 37 populations in this report , we have found direct evidence on the higher survival of the hbf rich erythrocytes in scd . 0 ###LEFT-WALL### 5 we 0 ###LEFT-WALL### 7 found 0 ###LEFT-WALL### 21 . 1 in 3 report 1 in 4 , 1 in 5 we 2 this 3 report 5 we 6 have 6 have 7 found 7 found 9 evidence 7 found 18 erythrocytes 7 found 19 in 8 direct 9 evidence 9 evidence 10 on 9 evidence 14 of 10 on 13 survival 11 the 13 survival 12 higher 13 survival 14 of 16 hbf 15 the 16 hbf 17 rich 18 erythrocytes 19 in 20 scd remission in elderly patients has been little studied . 0 ###LEFT-WALL### 1 remission 0 ###LEFT-WALL### 8 studied 0 ###LEFT-WALL### 9 . 1 remission 2 in 1 remission 5 has 2 in 4 patients 3 elderly 4 patients 5 has 6 been 6 been 7 little 6 been 8 studied the present analysis utilized a european database to focus on the elderly . 0 ###LEFT-WALL### 3 analysis 0 ###LEFT-WALL### 4 utilized 0 ###LEFT-WALL### 13 . 1 the 3 analysis 2 present 3 analysis 3 analysis 4 utilized 4 utilized 7 database 4 utilized 8 to 5 a 7 database 6 european 7 database 8 to 9 focus 9 focus 10 on 10 on 12 elderly 11 the 12 elderly using five different instruments examining remission , we report that aging did not adversely affect remission in the elderly . 0 ###LEFT-WALL### 8 we 0 ###LEFT-WALL### 9 report 0 ###LEFT-WALL### 20 . 1 using 4 instruments 1 using 7 , 1 using 8 we 2 five 4 instruments 3 different 4 instruments 4 instruments 5 examining 5 examining 6 remission 8 we 9 report 9 report 10 that 10 that 11 aging 10 that 15 affect 11 aging 12 did 12 did 13 not 12 did 15 affect 14 adversely 15 affect 15 affect 16 remission 15 affect 17 in 17 in 19 elderly 18 the 19 elderly management of elderly schizophrenia patients should thus be targeted towards remission . 0 ###LEFT-WALL### 1 management 0 ###LEFT-WALL### 9 targeted 0 ###LEFT-WALL### 12 . 1 management 2 of 1 management 6 should 2 of 5 patients 3 elderly 4 schizophrenia 4 schizophrenia 5 patients 6 should 8 be 7 thus 8 be 8 be 9 targeted 9 targeted 10 towards 10 towards 11 remission as taiwan has become the fastest aging country in the world , developing elderly - friendly health care services is of great importance . 0 ###LEFT-WALL### 13 developing 0 ###LEFT-WALL### 20 is 0 ###LEFT-WALL### 24 . 1 as 2 taiwan 1 as 4 become 1 as 12 , 1 as 13 developing 2 taiwan 3 has 3 has 4 become 4 become 8 country 4 become 9 in 5 the 6 fastest 5 the 8 country 7 aging 8 country 9 in 11 world 10 the 11 world 13 developing 19 services 13 developing 20 is 14 elderly 15 - 14 elderly 17 health 16 friendly 17 health 17 health 19 services 18 care 19 services 20 is 21 of 21 of 23 importance 22 great 23 importance compared with traditional health - care service models , healthcare needs of older people may differ extensively . 0 ###LEFT-WALL### 11 needs 0 ###LEFT-WALL### 16 differ 0 ###LEFT-WALL### 18 . 1 compared 2 with 1 compared 9 , 1 compared 11 needs 2 with 4 health 3 traditional 4 health 4 health 8 models 5 - 8 models 6 care 8 models 7 service 8 models 8 models 9 , 10 healthcare 11 needs 11 needs 12 of 11 needs 15 may 12 of 14 people 13 older 14 people 15 may 16 differ 16 differ 17 extensively it has been reported that geriatric evaluation and management ( gem ) , helps to differentiate the atypical presentations of frail older patients , to discover hidden health - social problems , and to [promote] long - term clinical outcome . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 13 , 0 ###LEFT-WALL### 24 , 1 it 2 has 2 has 3 been 3 been 13 , 4 reported 8 and 4 reported 13 , 5 that 7 evaluation 6 geriatric 7 evaluation 7 evaluation 8 and 8 and 9 management 8 and 11 gem 10 ( 11 gem 11 gem 12 ) 13 , 14 helps 14 helps 15 to 14 helps 16 differentiate 15 to 16 differentiate 16 differentiate 19 presentations 17 the 19 presentations 18 atypical 19 presentations 19 presentations 20 of 20 of 23 patients 21 frail 23 patients 22 older 23 patients 24 , 25 to 24 , 33 and 24 , 37 - 25 to 33 and 26 discover 28 health 26 discover 33 and 27 hidden 28 health 28 health 31 problems 29 - 31 problems 30 social 31 problems 31 problems 32 , 32 , 33 and 33 and 34 to 33 and 36 long 34 to 36 long 37 - 40 outcome 37 - 41 . 38 term 40 outcome 39 clinical 40 outcome the main purpose of this study was to explore the demographic characteristics of older patients visiting outpatient gem service and its impact to health - care utilization in a tertiary medical center in taiwan . 1 the 2 main 1 the 3 purpose 3 purpose 4 of 3 purpose 7 was 4 of 6 study 5 this 6 study 7 was 8 to 7 was 9 explore 8 to 9 explore 9 explore 12 characteristics 9 explore 23 to 10 the 12 characteristics 11 demographic 12 characteristics 12 characteristics 13 of 13 of 20 and 14 older 15 patients 15 patients 16 visiting 15 patients 20 and 16 visiting 19 service 17 outpatient 19 service 18 gem 19 service 20 and 22 impact 21 its 22 impact 23 to 24 health 24 health 27 utilization 25 - 27 utilization 26 care 27 utilization 27 utilization 28 in 27 utilization 35 . 28 in 32 center 29 a 30 tertiary 29 a 32 center 30 tertiary 32 center 31 medical 32 center 32 center 33 in 33 in 34 taiwan from january to october of 2008 , 1054 patients visited the outpatient gem service , and comprehensive geriatric assessment was performed for 140 patients ( 62.9 % males with the mean age [was] 81.0 ± 6.6 years ) , and 34.8 % of them were college graduates . 0 ###LEFT-WALL### 9 patients 0 ###LEFT-WALL### 10 visited 0 ###LEFT-WALL### 40 and 0 ###LEFT-WALL### 48 . 1 from 2 january 1 from 9 patients 3 to 4 october 3 to 7 , 3 to 9 patients 4 october 5 of 5 of 6 2008 8 1054 9 patients 9 patients 10 visited 10 visited 16 and 11 the 16 and 12 outpatient 14 service 13 gem 14 service 14 service 16 and 15 , 16 and 16 and 17 comprehensive 16 and 19 assessment 16 and 20 was 16 and 21 performed 16 and 22 for 18 geriatric 19 assessment 19 assessment 20 was 22 for 24 patients 23 140 24 patients 24 patients 28 males 25 ( 28 males 26 62.9 27 % 27 % 28 males 28 males 29 with 28 males 38 ) 29 with 37 years 30 the 37 years 31 mean 32 age 32 age 37 years 34 81.0 37 years 35 ± 37 years 36 6.6 37 years 39 , 40 and 40 and 42 % 40 and 45 were 41 34.8 42 % 42 % 43 of 42 % 45 were 43 of 44 them 45 were 47 graduates 46 college 47 graduates overall , the prevalence of functional impairment was 11.4 % , depressive symptoms 20.7 [%] , cognitive impairment 32.1 [%] , and abnormal timed up - and - go test 32.1 % . 0 ###LEFT-WALL### 4 prevalence 0 ###LEFT-WALL### 8 was 0 ###LEFT-WALL### 27 and 0 ###LEFT-WALL### 33 . 1 overall 2 , 1 overall 4 prevalence 3 the 4 prevalence 4 prevalence 5 of 4 prevalence 8 was 5 of 7 impairment 6 functional 7 impairment 8 was 10 % 9 11.4 10 % 10 % 22 and 11 , 22 and 12 depressive 13 symptoms 13 symptoms 14 20.7 13 symptoms 16 , 16 , 18 impairment 16 , 22 and 17 cognitive 18 impairment 18 impairment 19 32.1 21 , 22 and 22 and 23 abnormal 22 and 24 timed 22 and 26 - 24 timed 25 up 26 - 27 and 27 and 28 - 27 and 30 test 28 - 29 go 29 go 30 test 30 test 32 % 31 32.1 32 % in conclusion , patients visiting outpatient gem services in taiwan are old and well - educated , and they possessed various functional impairments . 0 ###LEFT-WALL### 2 conclusion 0 ###LEFT-WALL### 3 , 1 in 2 conclusion 3 , 8 services 3 , 11 are 3 , 15 - 4 patients 8 services 5 visiting 6 outpatient 6 outpatient 8 services 7 gem 8 services 8 services 9 in 8 services 11 are 9 in 10 taiwan 11 are 13 and 12 old 13 and 13 and 14 well 15 - 18 and 15 - 20 possessed 15 - 24 . 16 educated 18 and 17 , 18 and 18 and 19 they 18 and 20 possessed 20 possessed 23 impairments 21 various 23 impairments 22 functional 23 impairments the outpatient gem services significantly reduced the items of oral medications and improved quality of life . 0 ###LEFT-WALL### 4 services 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 17 . 1 the 4 services 2 outpatient 4 services 3 gem 4 services 4 services 12 and 5 significantly 6 reduced 6 reduced 8 items 6 reduced 12 and 7 the 8 items 8 items 9 of 9 of 11 medications 10 oral 11 medications 12 and 13 improved 13 improved 14 quality 14 quality 15 of 15 of 16 life the possible better compliance of this cohort due to high educational status may overestimate the clinical effectiveness of outpatient gem services . 0 ###LEFT-WALL### 4 compliance 0 ###LEFT-WALL### 14 overestimate 0 ###LEFT-WALL### 22 . 1 the 4 compliance 2 possible 4 compliance 3 better 4 compliance 4 compliance 5 of 4 compliance 13 may 5 of 7 cohort 6 this 7 cohort 7 cohort 9 to 8 due 9 to 9 to 12 status 10 high 12 status 11 educational 12 status 13 may 14 overestimate 14 overestimate 17 effectiveness 15 the 17 effectiveness 16 clinical 17 effectiveness 17 effectiveness 18 of 18 of 21 services 19 outpatient 21 services 20 gem 21 services further investigations are needed to clarify the long - term benefits of outpatient gem services . 0 ###LEFT-WALL### 2 investigations 0 ###LEFT-WALL### 4 needed 0 ###LEFT-WALL### 16 . 1 further 2 investigations 2 investigations 3 are 3 are 4 needed 4 needed 5 to 5 to 6 clarify 6 clarify 11 benefits 7 the 11 benefits 8 long 9 - 8 long 10 term 10 term 11 benefits 11 benefits 12 of 12 of 15 services 13 outpatient 15 services 14 gem 15 services the purpose of this study was to elucidate using time series analysis age and menopause induced differences in selected health quality related physiological factors . 0 ###LEFT-WALL### 2 purpose 0 ###LEFT-WALL### 14 and 0 ###LEFT-WALL### 25 . 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 elucidate 7 to 8 elucidate 8 elucidate 9 using 8 elucidate 13 age 9 using 10 time 11 series 13 age 12 analysis 13 age 14 and 17 differences 14 and 22 related 15 menopause 16 induced 16 induced 17 differences 17 differences 18 in 17 differences 22 related 18 in 21 quality 19 selected 20 health 20 health 21 quality 22 related 24 factors 23 physiological 24 factors the study was conducted , using the third national health and nutrition examination survey ( nhanes iii ) , and the nhanes 1999 - 2002 data , on women aged 35 - 60 . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 4 conducted 0 ###LEFT-WALL### 34 . 1 the 2 study 2 study 3 was 3 was 4 conducted 4 conducted 6 using 4 conducted 28 on 5 , 6 using 6 using 20 and 6 using 27 , 7 the 10 health 8 third 9 national 9 national 10 health 10 health 11 and 11 and 14 survey 11 and 16 nhanes 11 and 20 and 12 nutrition 13 examination 13 examination 14 survey 15 ( 16 nhanes 16 nhanes 17 iii 16 nhanes 18 ) 19 , 20 and 20 and 26 data 21 the 26 data 22 nhanes 24 - 22 nhanes 26 data 23 1999 24 - 24 - 25 2002 28 on 29 women 29 women 30 aged 30 aged 32 - 31 35 32 - 32 - 33 60 menopausal status was defined by months since the last period ( < 2 , 2 - 12 , and >12 months for pre - , peri - , and postmenopause , respectively ) . 0 ###LEFT-WALL### 1 menopausal 0 ###LEFT-WALL### 4 defined 0 ###LEFT-WALL### 34 . 1 menopausal 2 status 1 menopausal 3 was 1 menopausal 4 defined 2 status 3 was 4 defined 5 by 4 defined 7 since 4 defined 29 and 4 defined 32 respectively 5 by 6 months 8 the 10 period 9 last 10 period 10 period 13 2 10 period 16 - 10 period 19 and 11 ( 13 2 12 < 13 2 13 2 14 , 14 , 16 - 15 2 16 - 16 - 17 12 16 - 18 , 18 , 19 and 19 and 21 months 19 and 24 - 19 and 26 peri 19 and 29 and 20 >12 21 months 21 months 22 for 22 for 23 pre 25 , 26 peri 26 peri 27 - 28 , 29 and 29 and 30 postmenopause 31 , 32 respectively 32 respectively 33 ) the results indicate that postmenopausal women , aged less than 45 , are characterized by a decrease in systolic blood pressure ( sbp ) , an increase in high density lipoprotein ( hdl ) levels , and a decrease in triglyceride ( tg ) levels . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 indicate 0 ###LEFT-WALL### 25 , 0 ###LEFT-WALL### 46 . 1 the 2 results 2 results 3 indicate 3 indicate 6 women 3 indicate 14 characterized 4 that 5 postmenopausal 5 postmenopausal 6 women 6 women 8 aged 6 women 13 are 7 , 8 aged 8 aged 9 less 8 aged 10 than 8 aged 12 , 10 than 11 45 13 are 14 characterized 14 characterized 15 by 14 characterized 18 in 15 by 17 decrease 16 a 17 decrease 18 in 21 pressure 19 systolic 20 blood 20 blood 21 pressure 21 pressure 23 sbp 22 ( 23 sbp 23 sbp 24 ) 25 , 27 increase 25 , 35 levels 25 , 37 and 26 an 27 increase 27 increase 28 in 27 increase 35 levels 28 in 31 lipoprotein 29 high 31 lipoprotein 30 density 31 lipoprotein 31 lipoprotein 33 hdl 32 ( 33 hdl 33 hdl 34 ) 36 , 37 and 37 and 39 decrease 37 and 45 levels 38 a 39 decrease 39 decrease 40 in 39 decrease 45 levels 40 in 41 triglyceride 41 triglyceride 43 tg 42 ( 43 tg 43 tg 44 ) it was also determined that aging is the main factor leading to physiological variability in systolic blood pressure and high density lipoprotein levels , in pre - and perimenopausal women , and in follicle - stimulating [hormone] ( fsh ) activity in peri - and postmenopausal women . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 2 was 0 ###LEFT-WALL### 35 - 0 ###LEFT-WALL### 48 . 1 it 2 was 2 was 3 also 2 was 4 determined 4 determined 5 that 5 that 6 aging 5 that 7 is 6 aging 7 is 7 is 10 factor 7 is 12 to 7 is 15 in 8 the 10 factor 9 main 10 factor 10 factor 11 leading 12 to 14 variability 13 physiological 14 variability 15 in 19 and 16 systolic 17 blood 17 blood 18 pressure 18 pressure 19 and 19 and 23 levels 19 and 24 , 19 and 32 and 20 high 23 levels 21 density 23 levels 22 lipoprotein 23 levels 25 in 28 and 25 in 32 and 26 pre 28 and 27 - 28 and 28 and 30 women 29 perimenopausal 30 women 31 , 32 and 32 and 33 in 33 in 34 follicle 35 - 45 and 36 stimulating 39 fsh 36 stimulating 41 activity 38 ( 39 fsh 39 fsh 40 ) 41 activity 42 in 41 activity 45 and 42 in 43 peri 44 - 45 and 45 and 47 women 46 postmenopausal 47 women stoke remains a leading cause of death and disability with limited treatment options . 0 ###LEFT-WALL### 1 stoke 0 ###LEFT-WALL### 14 . 1 stoke 2 remains 2 remains 5 cause 2 remains 13 options 3 a 5 cause 4 leading 5 cause 5 cause 6 of 5 cause 13 options 6 of 8 and 7 death 8 and 8 and 9 disability 8 and 10 with 10 with 12 treatment 11 limited 12 treatment extensive research has been aimed at studying cell death events that [accompany] stroke and how to [use] these same cell death pathways as potential therapeutic targets for treating the disease . 0 ###LEFT-WALL### 2 research 0 ###LEFT-WALL### 5 aimed 0 ###LEFT-WALL### 31 . 1 extensive 2 research 2 research 3 has 3 has 4 been 4 been 5 aimed 5 aimed 6 at 5 aimed 23 as 6 at 7 studying 7 studying 22 pathways 8 cell 22 pathways 9 death 10 events 10 events 20 cell 11 that 13 stroke 13 stroke 14 and 14 and 15 how 14 and 16 to 14 and 20 cell 16 to 19 same 18 these 19 same 20 cell 22 pathways 21 death 22 pathways 23 as 26 targets 24 potential 26 targets 25 therapeutic 26 targets 26 targets 27 for 27 for 28 treating 28 treating 30 disease 29 the 30 disease the mitochondrial permeability transition pore ( mptp ) has been implicated as a major factor associated with stroke [-] induced neuronal cell death . 0 ###LEFT-WALL### 5 pore 0 ###LEFT-WALL### 11 implicated 0 ###LEFT-WALL### 24 . 1 the 5 pore 2 mitochondrial 5 pore 3 permeability 4 transition 4 transition 5 pore 5 pore 7 mptp 5 pore 9 has 6 ( 7 mptp 7 mptp 8 ) 9 has 10 been 10 been 11 implicated 11 implicated 12 as 11 implicated 17 with 12 as 15 factor 13 a 15 factor 14 major 15 factor 15 factor 16 associated 17 with 23 death 18 stroke 23 death 20 induced 22 cell 21 neuronal 22 cell 22 cell 23 death mptp activation and increased permeability has been shown to contribute to the events that lead to cell death . 0 ###LEFT-WALL### 2 activation 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 19 . 1 mptp 2 activation 3 and 5 permeability 3 and 8 shown 4 increased 5 permeability 5 permeability 6 has 6 has 7 been 7 been 8 shown 8 shown 9 to 9 to 10 contribute 10 contribute 11 to 11 to 13 events 12 the 13 events 13 events 14 that 13 events 15 lead 14 that 15 lead 15 lead 16 to 16 to 18 death 17 cell 18 death cyclosporine a ( csa ) , a widely used immunosuppressant in transplantation and rheumatic medicine , has been recently shown to possess neuroprotective properties through its ability to block the mptp , which in turn inhibits neuronal damage . 0 ###LEFT-WALL### 1 cyclosporine 0 ###LEFT-WALL### 20 shown 0 ###LEFT-WALL### 32 , 0 ###LEFT-WALL### 39 . 1 cyclosporine 2 a 1 cyclosporine 4 csa 1 cyclosporine 13 and 1 cyclosporine 17 has 3 ( 4 csa 4 csa 5 ) 6 , 13 and 7 a 10 immunosuppressant 8 widely 9 used 9 used 10 immunosuppressant 10 immunosuppressant 11 in 10 immunosuppressant 13 and 11 in 12 transplantation 13 and 15 medicine 13 and 16 , 14 rheumatic 15 medicine 17 has 18 been 18 been 19 recently 18 been 20 shown 20 shown 21 to 20 shown 25 through 21 to 22 possess 22 possess 24 properties 23 neuroprotective 24 properties 25 through 27 ability 26 its 27 ability 27 ability 28 to 27 ability 29 block 28 to 29 block 29 block 31 mptp 30 the 31 mptp 32 , 33 which 32 , 36 inhibits 33 which 36 inhibits 34 in 35 turn 35 turn 36 inhibits 36 inhibits 38 damage 37 neuronal 38 damage this newfound csa - mediated neuroprotection pathway prompted research on its use to prevent cell death in [stroke] and other neurological conditions . 0 ###LEFT-WALL### 3 csa 0 ###LEFT-WALL### 4 - 1 this 2 newfound 2 newfound 3 csa 4 - 19 and 4 - 23 . 5 mediated 6 neuroprotection 6 neuroprotection 8 prompted 7 pathway 8 prompted 8 prompted 9 research 9 research 10 on 9 research 19 and 10 on 12 use 11 its 12 use 12 use 13 to 12 use 17 in 13 to 14 prevent 14 prevent 16 death 14 prevent 17 in 15 cell 16 death 19 and 22 conditions 20 other 22 conditions 21 neurological 22 conditions preclinical studies are being conducted in hopes of establishing the safety and efficacy guidelines for csa use in human trials as a potential neuroprotective agent [against] stroke . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 3 are 0 ###LEFT-WALL### 28 . 1 preclinical 2 studies 2 studies 3 are 3 are 4 being 4 being 5 conducted 5 conducted 6 in 5 conducted 18 in 6 in 12 and 7 hopes 8 of 7 hopes 12 and 8 of 9 establishing 9 establishing 11 safety 10 the 11 safety 12 and 14 guidelines 12 and 15 for 13 efficacy 14 guidelines 15 for 17 use 16 csa 17 use 18 in 20 trials 19 human 20 trials 20 trials 21 as 21 as 27 stroke 22 a 27 stroke 23 potential 27 stroke 24 neuroprotective 27 stroke 25 agent 27 stroke in this review , we provide an overview of the current laboratory and clinical status of csa neuroprotection . 0 ###LEFT-WALL### 5 we 0 ###LEFT-WALL### 6 provide 0 ###LEFT-WALL### 19 . 1 in 3 review 1 in 4 , 1 in 5 we 2 this 3 review 5 we 6 provide 6 provide 8 overview 7 an 8 overview 8 overview 9 of 9 of 13 and 10 the 12 laboratory 11 current 12 laboratory 12 laboratory 13 and 13 and 15 status 13 and 16 of 14 clinical 15 status 16 of 18 neuroprotection 17 csa 18 neuroprotection objective : to examine race/ethnicity and neighborhood income differences in longitudinal patterns of deterioration in hemoglobin a1c ( hba1c ) values among youth ( age 10 to 18 years ) with type 1 diabetes . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 21 values 0 ###LEFT-WALL### 35 . 1 objective 2 : 2 : 3 to 2 : 4 examine 3 to 4 examine 4 examine 6 and 4 examine 10 in 5 race/ethnicity 6 and 6 and 9 differences 7 neighborhood 8 income 8 income 9 differences 10 in 12 patterns 11 longitudinal 12 patterns 12 patterns 13 of 13 of 14 deterioration 14 deterioration 15 in 15 in 16 hemoglobin 16 hemoglobin 17 a1c 16 hemoglobin 21 values 17 a1c 19 hba1c 17 a1c 21 values 18 ( 19 hba1c 19 hba1c 20 ) 21 values 22 among 21 values 31 with 22 among 23 youth 23 youth 29 years 24 ( 29 years 25 age 27 to 25 age 29 years 26 10 27 to 27 to 28 18 29 years 30 ) 31 with 32 type 31 with 34 diabetes 32 type 33 1 study design : a sample of 225 youth ( 50.2 % [female] ) , including 81 white , 81 black , and 63 hispanic youth with type 1 diabetes , was matched initially on age and sex . 0 ###LEFT-WALL### 2 design 0 ###LEFT-WALL### 14 , 1 study 2 design 2 design 3 : 3 : 5 sample 4 a 5 sample 5 sample 6 of 5 sample 11 % 6 of 8 youth 7 225 8 youth 9 ( 11 % 10 50.2 11 % 11 % 13 ) 14 , 15 including 14 , 32 matched 15 including 17 white 15 including 31 was 15 including 32 matched 16 81 17 white 17 white 29 diabetes 17 white 31 was 18 , 29 diabetes 19 81 20 black 20 black 22 and 21 , 22 and 22 and 25 youth 22 and 29 diabetes 23 63 24 hispanic 24 hispanic 25 youth 25 youth 26 with 26 with 27 type 27 type 28 1 29 diabetes 30 , 32 matched 33 initially 32 matched 34 on 34 on 36 and 35 age 36 and 36 and 37 sex 36 and 38 . neighborhood median family income was obtained through public census databases . 0 ###LEFT-WALL### 4 income 0 ###LEFT-WALL### 6 obtained 0 ###LEFT-WALL### 11 . 1 neighborhood 4 income 2 median 3 family 3 family 4 income 4 income 5 was 5 was 6 obtained 6 obtained 7 through 7 through 10 databases 8 public 9 census 9 census 10 databases self - identified race/ethnicity and all hba1c values ( grand mean , 9.09 % ± 2.02 % [ )(available in patients ' medical records between age 10 and 18 years were recorded and analyzed . 0 ###LEFT-WALL### 1 self 0 ###LEFT-WALL### 2 - 2 - 5 and 3 identified 4 race/ethnicity 4 race/ethnicity 5 and 5 and 8 values 5 and 15 ± 6 all 8 values 7 hba1c 8 values 9 ( 15 ± 10 grand 15 ± 11 mean 12 , 11 mean 15 ± 13 9.09 14 % 14 % 15 ± 15 ± 17 % 15 ± 24 records 15 ± 35 . 16 2.02 17 % 17 % 19 )(available 17 % 24 records 19 )(available 20 in 20 in 23 medical 21 patients 22 ' 22 ' 23 medical 24 records 25 between 25 between 26 age 26 age 28 and 27 10 28 and 28 and 29 18 29 18 30 years 30 years 31 were 31 were 33 and 32 recorded 33 and 33 and 34 analyzed results : hierarchical linear modeling revealed age - related deterioration in hba1c values that differed by race/ethnicity and income . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 9 related 1 results 2 : 2 : 7 age 3 hierarchical 5 modeling 4 linear 5 modeling 5 modeling 6 revealed 6 revealed 7 age 8 - 9 related 9 related 10 deterioration 9 related 11 in 9 related 16 by 9 related 20 . 11 in 13 values 12 hba1c 13 values 13 values 14 that 13 values 15 differed 14 that 15 differed 16 by 18 and 17 race/ethnicity 18 and 18 and 19 income controlling for income , white and hispanic youth had similar hba1c values at the start of adolescence ( age 10 ) and demonstrated similar rates of deterioration across adolescence . 0 ###LEFT-WALL### 1 controlling 0 ###LEFT-WALL### 9 had 0 ###LEFT-WALL### 30 . 1 controlling 2 for 1 controlling 8 youth 1 controlling 9 had 2 for 6 and 3 income 4 , 4 , 5 white 4 , 6 and 6 and 7 hispanic 9 had 12 values 9 had 13 at 9 had 28 across 10 similar 12 values 11 hba1c 12 values 13 at 22 and 14 the 15 start 15 start 16 of 15 start 22 and 16 of 17 adolescence 17 adolescence 19 age 18 ( 19 age 19 age 20 10 19 age 21 ) 22 and 25 rates 22 and 26 of 23 demonstrated 25 rates 24 similar 25 rates 26 of 27 deterioration 28 across 29 adolescence blacks had higher initial hba1c values compared with whites and hispanics , but a similar rate of deterioration . 0 ###LEFT-WALL### 1 blacks 0 ###LEFT-WALL### 2 had 1 blacks 2 had 2 had 6 values 2 had 8 with 2 had 13 but 3 higher 4 initial 4 initial 6 values 5 hba1c 6 values 6 values 7 compared 8 with 10 and 9 whites 10 and 10 and 11 hispanics 12 , 13 but 13 but 16 rate 13 but 19 . 14 a 15 similar 14 a 16 rate 15 similar 16 rate 16 rate 17 of 17 of 18 deterioration higher neighborhood income was associated with slower deterioration in hba1c value among white teens , but not among hispanic or black teens . 0 ###LEFT-WALL### 3 income 0 ###LEFT-WALL### 5 associated 0 ###LEFT-WALL### 23 . 1 higher 2 neighborhood 2 neighborhood 3 income 3 income 4 was 4 was 5 associated 5 associated 6 with 5 associated 9 in 6 with 8 deterioration 7 slower 8 deterioration 9 in 11 value 10 hba1c 11 value 11 value 16 but 12 among 14 teens 12 among 16 but 13 white 14 teens 15 , 16 but 16 but 17 not 16 but 18 among 18 among 20 or 19 hispanic 20 or 20 or 22 teens 21 black 22 teens conclusions : longitudinally , black youth [appear] to experience disproportionate risks compared with white and hispanic youth when income is statistically controlled . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 23 . 2 : 6 youth 2 : 12 compared 3 longitudinally 4 , 3 longitudinally 6 youth 5 black 6 youth 6 youth 8 to 6 youth 9 experience 6 youth 12 compared 8 to 9 experience 9 experience 11 risks 10 disproportionate 11 risks 12 compared 13 with 12 compared 18 when 13 with 15 and 14 white 15 and 15 and 17 youth 16 hispanic 17 youth 18 when 19 income 18 when 20 is 19 income 20 is 20 is 22 controlled 21 statistically 22 controlled neither black nor hispanic youth appear to benefit from living in higher - income neighborhoods . 0 ###LEFT-WALL### 3 nor 0 ###LEFT-WALL### 6 appear 0 ###LEFT-WALL### 16 . 1 neither 3 nor 2 black 3 nor 3 nor 5 youth 3 nor 6 appear 4 hispanic 5 youth 6 appear 7 to 6 appear 8 benefit 7 to 8 benefit 8 benefit 9 from 9 from 10 living 10 living 11 in 11 in 15 neighborhoods 12 higher 13 - 12 higher 14 income 14 income 15 neighborhoods background : data [from] the us indicates that methadone - maintained populations are aging , with an increase of patients aged 50 or older . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 25 . 1 background 2 : 2 : 23 or 3 data 14 aging 3 data 16 with 3 data 23 or 5 the 6 us 6 us 7 indicates 7 indicates 8 that 8 that 12 populations 8 that 14 aging 9 methadone 10 - 9 methadone 12 populations 11 maintained 12 populations 12 populations 13 are 13 are 14 aging 14 aging 15 , 16 with 18 increase 17 an 18 increase 18 increase 19 of 19 of 20 patients 20 patients 21 aged 21 aged 22 50 23 or 24 older data from european methadone populations is sparse . 0 ###LEFT-WALL### 1 data 0 ###LEFT-WALL### 6 is 0 ###LEFT-WALL### 8 . 1 data 2 from 1 data 6 is 2 from 5 populations 3 european 5 populations 4 methadone 5 populations 6 is 7 sparse this retrospective cohort study sought to evaluate the age trends and related developments in the methadone population of basel - city , switzerland . 0 ###LEFT-WALL### 4 study 0 ###LEFT-WALL### 5 sought 0 ###LEFT-WALL### 24 . 1 this 4 study 2 retrospective 3 cohort 3 cohort 4 study 4 study 5 sought 5 sought 6 to 5 sought 7 evaluate 6 to 7 evaluate 7 evaluate 9 age 8 the 9 age 9 age 11 and 10 trends 11 and 11 and 12 related 11 and 23 switzerland 12 related 13 developments 12 related 14 in 14 in 17 population 15 the 17 population 16 methadone 17 population 17 population 18 of 18 of 19 basel 19 basel 21 city 20 - 21 city 21 city 22 , methods : the study included methadone patients between april 1 , 1995 and [march] 31 , 2003 . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 16 , 0 ###LEFT-WALL### 18 . 1 methods 2 : 2 : 7 patients 3 the 7 patients 4 study 5 included 5 included 7 patients 6 methadone 7 patients 7 patients 8 between 7 patients 13 and 8 between 9 april 9 april 10 1 11 , 13 and 12 1995 13 and 13 and 15 31 13 and 16 , 16 , 17 2003 anonymized data was taken from the methadone register of basel - city . 0 ###LEFT-WALL### 2 data 0 ###LEFT-WALL### 4 taken 0 ###LEFT-WALL### 11 - 1 anonymized 2 data 2 data 3 was 3 was 4 taken 4 taken 5 from 5 from 8 register 6 the 8 register 7 methadone 8 register 8 register 9 of 9 of 10 basel 11 - 12 city 11 - 13 . for analysis of age distributions , patient samples were split into four age categories from ['] 20 - 29 years ' to ['] 50 years [and] [over] ['] . 0 ###LEFT-WALL### 8 samples 0 ###LEFT-WALL### 10 split 0 ###LEFT-WALL### 29 . 1 for 2 analysis 1 for 6 , 1 for 8 samples 2 analysis 3 of 3 of 5 distributions 4 age 5 distributions 7 patient 8 samples 8 samples 9 were 9 were 10 split 10 split 11 into 10 split 15 from 10 split 22 to 11 into 14 categories 12 four 14 categories 13 age 14 categories 15 from 21 ' 17 20 18 - 18 - 19 29 18 - 20 years 20 years 21 ' 22 to 25 years 24 50 25 years cross - sectional comparisons were performed using patient samples of 1996 and 2003 . 0 ###LEFT-WALL### 4 comparisons 0 ###LEFT-WALL### 6 performed 0 ###LEFT-WALL### 14 . 1 cross 2 - 1 cross 4 comparisons 3 sectional 4 comparisons 4 comparisons 5 were 5 were 6 performed 6 performed 7 using 7 using 9 samples 8 patient 9 samples 9 samples 10 of 10 of 12 and 11 1996 12 and 12 and 13 2003 results : analysis showed a significant increase in older patients between 1996 and 2003 ( p < 0.001 ) . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 3 analysis 2 : 4 showed 2 : 20 . 3 analysis 4 showed 4 showed 7 increase 4 showed 8 in 5 a 6 significant 5 a 7 increase 6 significant 7 increase 8 in 10 patients 9 older 10 patients 10 patients 13 and 10 patients 17 < 11 between 13 and 12 1996 13 and 13 and 14 2003 15 ( 17 < 16 p 17 < 17 < 18 0.001 17 < 19 ) during that period , the percentage of patients aged 50 and [over] rose almost tenfold , while the proportion of patients aged under 30 dropped significantly from 52.8 % to 12.3 % . 0 ###LEFT-WALL### 6 percentage 0 ###LEFT-WALL### 11 and 1 during 3 period 1 during 4 , 1 during 6 percentage 2 that 3 period 5 the 6 percentage 6 percentage 7 of 6 percentage 11 and 7 of 8 patients 9 aged 10 50 9 aged 11 and 11 and 13 rose 11 and 15 tenfold 11 and 17 while 14 almost 15 tenfold 16 , 17 while 17 while 19 proportion 17 while 22 aged 17 while 33 . 18 the 19 proportion 19 proportion 20 of 19 proportion 22 aged 20 of 21 patients 22 aged 23 under 23 under 24 30 24 30 25 dropped 25 dropped 26 significantly 25 dropped 27 from 25 dropped 30 to 27 from 29 % 28 52.8 29 % 30 to 32 % 31 12.3 32 % the average methadone [dose] ( p < 0.001 ) and the 1 [-] year retention rate ( p < 0.001 ) also increased significantly . 0 ###LEFT-WALL### 2 average 0 ###LEFT-WALL### 3 methadone 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 25 . 1 the 2 average 2 average 3 methadone 3 methadone 7 < 5 ( 7 < 6 p 7 < 7 < 8 0.001 7 < 9 ) 10 and 16 rate 10 and 23 increased 11 the 12 1 12 1 16 rate 14 year 16 rate 15 retention 16 rate 16 rate 19 < 16 rate 23 increased 17 ( 19 < 18 p 19 < 19 < 20 0.001 19 < 21 ) 22 also 23 increased 23 increased 24 significantly conclusions : findings point to clear trends in aging of methadone patients in basel [-] city which are comparable , [although] less pronounced , to developments among us methadone populations . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 6 clear 0 ###LEFT-WALL### 31 . 2 : 3 findings 2 : 4 point 3 findings 4 point 4 point 5 to 5 to 6 clear 6 clear 7 trends 6 clear 8 in 6 clear 10 of 8 in 9 aging 10 of 12 patients 11 methadone 12 patients 12 patients 13 in 12 patients 17 which 12 patients 18 are 12 patients 25 to 13 in 16 city 14 basel 16 city 17 which 18 are 18 are 19 comparable 19 comparable 23 pronounced 20 , 22 less 20 , 23 pronounced 23 pronounced 24 , 25 to 26 developments 26 developments 27 among 27 among 30 populations 28 us 29 methadone 29 methadone 30 populations many unanswered questions on medical , psychosocial and health economic consequences remain as the needs of older patients have not yet been evaluated extensively . 0 ###LEFT-WALL### 3 questions 0 ###LEFT-WALL### 23 evaluated 0 ###LEFT-WALL### 25 . 1 many 3 questions 2 unanswered 3 questions 3 questions 4 on 3 questions 11 consequences 3 questions 12 remain 3 questions 19 have 4 on 8 and 5 medical 6 , 6 , 7 psychosocial 6 , 8 and 8 and 9 health 10 economic 11 consequences 11 consequences 12 remain 12 remain 13 as 13 as 15 needs 14 the 15 needs 15 needs 16 of 16 of 18 patients 17 older 18 patients 19 have 20 not 19 have 22 been 21 yet 22 been 22 been 23 evaluated 23 evaluated 24 extensively however , older methadone patients , just as any other patients , should be accorded treatment appropriate to their medical condition and needs . 0 ###LEFT-WALL### 5 patients 0 ###LEFT-WALL### 22 and 0 ###LEFT-WALL### 24 . 1 however 2 , 1 however 5 patients 3 older 5 patients 4 methadone 5 patients 5 patients 7 just 5 patients 22 and 6 , 7 just 7 just 8 as 7 just 12 , 8 as 11 patients 9 any 10 other 10 other 11 patients 13 should 14 be 13 should 22 and 14 be 15 accorded 15 accorded 16 treatment 16 treatment 17 appropriate 17 appropriate 18 to 18 to 21 condition 19 their 21 condition 20 medical 21 condition 22 and 23 needs particular attention should be paid to adequate solutions for persons in need of care . 0 ###LEFT-WALL### 2 attention 0 ###LEFT-WALL### 5 paid 0 ###LEFT-WALL### 15 . 1 particular 2 attention 2 attention 3 should 3 should 4 be 4 be 5 paid 5 paid 6 to 5 paid 11 in 6 to 8 solutions 7 adequate 8 solutions 8 solutions 9 for 9 for 10 persons 11 in 12 need 12 need 13 of 13 of 14 care senile purpura occurs because of a weakness of the vascular supporting tissues mainly caused by aging and is most often seen on the dorsal surface of the hands and the extensor surfaces of the forearms , and has also been observed in the oral mucosa of elderly patients . 0 ###LEFT-WALL### 2 purpura 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 49 . 1 senile 2 purpura 2 purpura 17 and 3 occurs 4 because 3 occurs 15 by 3 occurs 17 and 4 because 5 of 5 of 7 weakness 6 a 7 weakness 7 weakness 8 of 7 weakness 11 supporting 8 of 10 vascular 9 the 10 vascular 11 supporting 12 tissues 12 tissues 14 caused 13 mainly 14 caused 15 by 16 aging 17 and 37 and 18 is 29 and 18 is 37 and 19 most 21 seen 19 most 29 and 20 often 21 seen 21 seen 22 on 22 on 25 surface 23 the 25 surface 24 dorsal 25 surface 25 surface 26 of 26 of 28 hands 27 the 28 hands 29 and 32 surfaces 29 and 33 of 30 the 32 surfaces 31 extensor 32 surfaces 33 of 35 forearms 34 the 35 forearms 36 , 37 and 37 and 38 has 38 has 40 been 39 also 40 been 40 been 41 observed 41 observed 42 in 42 in 45 mucosa 43 the 45 mucosa 44 oral 45 mucosa 45 mucosa 46 of 46 of 48 patients 47 elderly 48 patients these red lesions present as sharply margined subcutaneous hemorrhagic spots and [are] due to trauma , such as damage to the endothelium of small blood vessels , or a coagulation defect . 0 ###LEFT-WALL### 28 or 0 ###LEFT-WALL### 32 . 1 these 3 lesions 2 red 3 lesions 3 lesions 4 present 3 lesions 28 or 4 present 5 as 4 present 14 to 5 as 11 and 6 sharply 7 margined 7 margined 10 spots 8 subcutaneous 10 spots 9 hemorrhagic 10 spots 10 spots 11 and 11 and 13 due 14 to 15 trauma 15 trauma 18 as 16 , 18 as 17 such 18 as 18 as 19 damage 18 as 27 , 19 damage 20 to 19 damage 23 of 20 to 22 endothelium 21 the 22 endothelium 23 of 26 vessels 24 small 25 blood 25 blood 26 vessels 28 or 31 defect 29 a 31 defect 30 coagulation 31 defect they can also be due to reduced perivascular support , or capillary fragility and permeability , or a combination of all of these factors . 0 ###LEFT-WALL### 1 they 0 ###LEFT-WALL### 4 be 0 ###LEFT-WALL### 25 . 1 they 2 can 2 can 4 be 3 also 4 be 4 be 6 to 5 due 6 to 6 to 17 or 7 reduced 9 support 8 perivascular 9 support 9 support 11 or 10 , 11 or 11 or 13 fragility 11 or 14 and 12 capillary 13 fragility 14 and 15 permeability 14 and 17 or 16 , 17 or 17 or 19 combination 18 a 19 combination 19 combination 20 of 20 of 21 all 21 all 22 of 22 of 24 factors 23 these 24 factors oral manifestation [of] senile purpura can also be induced by long periods of medication use leading to fragile areas of the mucosa . 0 ###LEFT-WALL### 5 purpura 0 ###LEFT-WALL### 9 induced 0 ###LEFT-WALL### 23 . 1 oral 2 manifestation 2 manifestation 5 purpura 4 senile 5 purpura 5 purpura 6 can 6 can 8 be 7 also 8 be 8 be 9 induced 9 induced 10 by 10 by 12 periods 11 long 12 periods 12 periods 13 of 13 of 15 use 14 medication 15 use 15 use 16 leading 16 leading 17 to 17 to 19 areas 18 fragile 19 areas 19 areas 20 of 20 of 22 mucosa 21 the 22 mucosa the presence of senile purpura requires continuous [follow] - up [since] drug [-] induced purpura may cause plaque function alterations . 0 ###LEFT-WALL### 2 presence 0 ###LEFT-WALL### 6 requires 0 ###LEFT-WALL### 21 . 1 the 2 presence 2 presence 3 of 2 presence 6 requires 3 of 5 purpura 4 senile 5 purpura 6 requires 15 purpura 6 requires 17 cause 7 continuous 9 - 7 continuous 12 drug 10 up 12 drug 12 drug 14 induced 14 induced 15 purpura 15 purpura 16 may 16 may 17 cause 17 cause 20 alterations 18 plaque 20 alterations 19 function 20 alterations an accurate diagnosis in elderly complete denture wearers can minimize bleeding and prevent possible development of ulcerations under the dentures , especially during the adaptation period to the prosthesis . 0 ###LEFT-WALL### 3 diagnosis 0 ###LEFT-WALL### 12 and 1 an 2 accurate 1 an 3 diagnosis 2 accurate 3 diagnosis 3 diagnosis 4 in 3 diagnosis 9 can 4 in 8 wearers 5 elderly 7 denture 6 complete 7 denture 7 denture 8 wearers 9 can 12 and 10 minimize 11 bleeding 10 minimize 12 and 12 and 13 prevent 13 prevent 15 development 13 prevent 18 under 14 possible 15 development 15 development 16 of 16 of 17 ulcerations 18 under 20 dentures 19 the 20 dentures 20 dentures 23 during 21 , 22 especially 21 , 23 during 23 during 26 period 23 during 30 . 24 the 26 period 25 adaptation 26 period 26 period 27 to 27 to 29 prosthesis 28 the 29 prosthesis this case report [,] presents the care and 3 - [year] follow - up [of] a 66 [-] year [-] old woman with complete dentures who presented with the oral manifestations of senile purpura caused by the continued use of several medications . 0 ###LEFT-WALL### 3 report 0 ###LEFT-WALL### 5 presents 0 ###LEFT-WALL### 8 and 1 this 3 report 2 case 3 report 3 report 5 presents 5 presents 7 care 6 the 7 care 8 and 9 3 8 and 10 - 9 3 10 - 10 - 12 follow 12 follow 14 up 13 - 14 up 14 up 22 woman 14 up 43 . 16 a 22 woman 17 66 19 year 19 year 22 woman 21 old 22 woman 22 woman 23 with 22 woman 26 who 22 woman 27 presented 22 woman 32 of 23 with 25 dentures 24 complete 25 dentures 26 who 27 presented 27 presented 28 with 27 presented 31 manifestations 28 with 30 oral 29 the 30 oral 32 of 34 purpura 33 senile 34 purpura 34 purpura 35 caused 34 purpura 40 of 35 caused 36 by 36 by 39 use 37 the 39 use 38 continued 39 use 40 of 42 medications 41 several 42 medications none the aim of this study was to evaluate if portuguese patients with familial amyloidosis , liver transplanted [and] [not] , have an earlier development of presbyopia compared with a normal population and its relation with the presence or the absence of anterior capsule opacification of the lens . 0 ###LEFT-WALL### 1 none 0 ###LEFT-WALL### 28 compared 0 ###LEFT-WALL### 49 . 1 none 3 aim 1 none 9 evaluate 1 none 28 compared 2 the 3 aim 3 aim 4 of 3 aim 7 was 4 of 6 study 5 this 6 study 7 was 8 to 7 was 9 evaluate 8 to 9 evaluate 9 evaluate 10 if 10 if 12 patients 10 if 22 have 11 portuguese 12 patients 12 patients 13 with 12 patients 22 have 13 with 15 amyloidosis 14 familial 15 amyloidosis 15 amyloidosis 17 liver 16 , 17 liver 17 liver 18 transplanted 17 liver 21 , 22 have 25 development 23 an 25 development 24 earlier 25 development 25 development 26 of 26 of 27 presbyopia 28 compared 29 with 28 compared 36 with 29 with 33 and 30 a 31 normal 30 a 32 population 31 normal 32 population 32 population 33 and 33 and 35 relation 34 its 35 relation 36 with 39 or 37 the 38 presence 38 presence 39 or 39 or 41 absence 39 or 42 of 40 the 41 absence 42 of 45 opacification 43 anterior 44 capsule 44 capsule 45 opacification 45 opacification 46 of 46 of 48 lens 47 the 48 lens this study was performed to evaluate if portuguese patients with familial amyloidosis and in a blood donors population [(] control group [ )( 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 4 performed 0 ###LEFT-WALL### 23 )( 1 this 2 study 2 study 3 was 3 was 4 performed 4 performed 5 to 5 to 6 evaluate 6 evaluate 7 if 7 if 9 patients 7 if 21 group 8 portuguese 9 patients 9 patients 13 and 9 patients 21 group 10 with 12 amyloidosis 10 with 13 and 11 familial 12 amyloidosis 13 and 14 in 14 in 20 control 15 a 16 blood 15 a 20 control 16 blood 20 control 17 donors 20 control 18 population 20 control three hundred and fifty - six subjects , 144 amyloidotic patients and 212 healthy individuals , were evaluated for the need of plus lenses for normal near reading ( jaeger chart 1 at 33 cm ) . 0 ###LEFT-WALL### 4 fifty 0 ###LEFT-WALL### 18 evaluated 0 ###LEFT-WALL### 37 . 1 three 2 hundred 2 hundred 3 and 3 and 4 fifty 4 fifty 12 and 4 fifty 17 were 5 - 12 and 6 six 7 subjects 7 subjects 8 , 8 , 11 patients 8 , 12 and 9 144 11 patients 10 amyloidotic 11 patients 12 and 15 individuals 12 and 16 , 13 212 15 individuals 14 healthy 15 individuals 17 were 18 evaluated 18 evaluated 19 for 19 for 21 need 20 the 21 need 21 need 22 of 22 of 23 plus 23 plus 24 lenses 24 lenses 25 for 25 for 28 reading 26 normal 28 reading 27 near 28 reading 28 reading 31 chart 29 ( 31 chart 30 jaeger 31 chart 31 chart 32 1 31 chart 33 at 31 chart 36 ) 33 at 35 cm 34 33 35 cm in familial amyloidosis patients , the value of the [add] [-] power was related to age , liver transplantation status , and presence of visible anterior capsule opacification of the lens . 0 ###LEFT-WALL### 7 value 0 ###LEFT-WALL### 14 related 0 ###LEFT-WALL### 32 . 1 in 4 patients 1 in 5 , 1 in 7 value 2 familial 3 amyloidosis 3 amyloidosis 4 patients 6 the 7 value 7 value 8 of 7 value 13 was 8 of 12 power 9 the 12 power 13 was 14 related 14 related 15 to 15 to 22 and 16 age 17 , 17 , 20 status 17 , 22 and 18 liver 20 status 19 transplantation 20 status 21 , 22 and 22 and 23 presence 22 and 24 of 24 of 28 opacification 25 visible 27 capsule 26 anterior 27 capsule 27 capsule 28 opacification 28 opacification 29 of 29 of 31 lens 30 the 31 lens in both groups , the value of [add] [-] power was positively correlated with age ( r=0.91 ; p<0.005 [ )( 0 ###LEFT-WALL### 6 value 0 ###LEFT-WALL### 13 correlated 0 ###LEFT-WALL### 18 ; 0 ###LEFT-WALL### 21 )( 1 in 3 groups 1 in 4 , 1 in 6 value 2 both 3 groups 5 the 6 value 6 value 7 of 6 value 11 was 7 of 10 power 11 was 12 positively 11 was 13 correlated 13 correlated 14 with 14 with 15 age 15 age 17 r=0.91 16 ( 17 r=0.91 17 r=0.91 18 ; 18 ; 19 p<0.005 familial amyloidosis patients require more add - power than control individuals of similar age , and need to use reading glasses at earlier ages . 0 ###LEFT-WALL### 3 patients 0 ###LEFT-WALL### 4 require 0 ###LEFT-WALL### 7 - 0 ###LEFT-WALL### 19 use 0 ###LEFT-WALL### 25 . 1 familial 2 amyloidosis 2 amyloidosis 3 patients 3 patients 4 require 4 require 5 more 4 require 6 add 5 more 6 add 7 - 8 power 8 power 9 than 8 power 11 individuals 8 power 18 to 10 control 11 individuals 11 individuals 12 of 12 of 16 and 13 similar 14 age 14 age 16 and 15 , 16 and 16 and 17 need 18 to 19 use 19 use 21 glasses 20 reading 21 glasses 21 glasses 22 at 22 at 24 ages 23 earlier 24 ages the age of onset [of] presbyopia in familial amyloidosis patients was significantly lower than in control individuals ( 32 years vs [.] 42 years ) . 0 ###LEFT-WALL### 2 age 0 ###LEFT-WALL### 11 was 0 ###LEFT-WALL### 26 . 1 the 2 age 2 age 3 of 2 age 11 was 3 of 6 presbyopia 4 onset 6 presbyopia 6 presbyopia 7 in 7 in 10 patients 8 familial 9 amyloidosis 9 amyloidosis 10 patients 11 was 12 significantly 11 was 13 lower 13 lower 14 than 14 than 15 in 15 in 17 individuals 16 control 17 individuals 17 individuals 20 years 18 ( 20 years 19 32 20 years 20 years 21 vs 20 years 25 ) 21 vs 24 years 23 42 24 years adjusting for age , no significant difference was observed in [add] [-] power values between liver transplanted and not transplanted amyloidotic patients , suggesting that liver transplantation has no influence on presbyopia evolution in these patients . 0 ###LEFT-WALL### 7 difference 0 ###LEFT-WALL### 9 observed 0 ###LEFT-WALL### 18 and 0 ###LEFT-WALL### 37 . 1 adjusting 2 for 1 adjusting 4 , 1 adjusting 7 difference 2 for 3 age 5 no 7 difference 6 significant 7 difference 7 difference 8 was 8 was 9 observed 9 observed 10 in 9 observed 15 between 10 in 14 values 13 power 14 values 15 between 16 liver 16 liver 17 transplanted 18 and 19 not 18 and 24 suggesting 18 and 28 has 19 not 20 transplanted 20 transplanted 22 patients 20 transplanted 23 , 21 amyloidotic 22 patients 24 suggesting 27 transplantation 24 suggesting 28 has 25 that 27 transplantation 26 liver 27 transplantation 28 has 30 influence 28 has 31 on 28 has 34 in 29 no 30 influence 31 on 33 evolution 32 presbyopia 33 evolution 34 in 36 patients 35 these 36 patients familial amyloidosis patients had an earlier onset of presbyopia , probably related to amyloid deposition on the anterior capsule of the lens , which is not halted by liver transplantation . 0 ###LEFT-WALL### 3 patients 0 ###LEFT-WALL### 4 had 0 ###LEFT-WALL### 23 , 0 ###LEFT-WALL### 31 . 1 familial 2 amyloidosis 2 amyloidosis 3 patients 3 patients 4 had 4 had 7 onset 4 had 12 related 5 an 7 onset 6 earlier 7 onset 7 onset 8 of 8 of 9 presbyopia 10 , 12 related 11 probably 12 related 12 related 13 to 12 related 16 on 12 related 23 , 13 to 15 deposition 14 amyloid 15 deposition 16 on 19 capsule 17 the 19 capsule 18 anterior 19 capsule 19 capsule 20 of 20 of 22 lens 21 the 22 lens 23 , 24 which 23 , 25 is 24 which 25 is 25 is 26 not 25 is 28 by 26 not 27 halted 28 by 30 transplantation 29 liver 30 transplantation animals living in an impoverished environment , i.e [.] , without the possibility of physical and social activity , perform [worse] on cognitive tests compared to animals in an enriched environment . 0 ###LEFT-WALL### 1 animals 0 ###LEFT-WALL### 20 perform 0 ###LEFT-WALL### 32 . 1 animals 2 living 1 animals 20 perform 2 living 3 in 3 in 6 environment 4 an 6 environment 5 impoverished 6 environment 6 environment 8 i.e 6 environment 11 without 7 , 8 i.e 8 i.e 10 , 10 , 11 without 11 without 13 possibility 11 without 19 , 12 the 13 possibility 13 possibility 14 of 14 of 18 activity 15 physical 16 and 16 and 17 social 16 and 18 activity 20 perform 22 on 20 perform 26 to 22 on 24 tests 23 cognitive 24 tests 24 tests 25 compared 26 to 27 animals 27 animals 28 in 28 in 31 environment 29 an 31 environment 30 enriched 31 environment the same cognitive difference is also observed in humans . 0 ###LEFT-WALL### 4 difference 0 ###LEFT-WALL### 7 observed 0 ###LEFT-WALL### 10 . 1 the 2 same 2 same 4 difference 3 cognitive 4 difference 4 difference 5 is 5 is 6 also 5 is 7 observed 7 observed 8 in 8 in 9 humans however , it is not clear whether this difference is caused by a decrease in cognition due to an impoverished environment or an increase due to an enriched environment . 0 ###LEFT-WALL### 3 it 0 ###LEFT-WALL### 4 is 0 ###LEFT-WALL### 30 . 1 however 2 , 1 however 3 it 3 it 4 is 4 is 5 not 4 is 6 clear 5 not 6 clear 6 clear 7 whether 7 whether 9 difference 7 whether 11 caused 8 this 9 difference 9 difference 10 is 10 is 11 caused 11 caused 12 by 11 caused 15 in 11 caused 18 to 12 by 14 decrease 13 a 14 decrease 15 in 16 cognition 17 due 18 to 18 to 22 or 19 an 21 environment 20 impoverished 21 environment 21 environment 22 or 22 or 24 increase 22 or 26 to 23 an 24 increase 25 due 26 to 26 to 29 environment 27 an 29 environment 28 enriched 29 environment this review discusses the impact of an impoverished environment on cognition in animal experimental studies and human experimental studies with community [-] dwelling and institutionalized older people . 0 ###LEFT-WALL### 2 review 0 ###LEFT-WALL### 24 and 0 ###LEFT-WALL### 28 . 1 this 2 review 2 review 24 and 3 discusses 5 impact 3 discusses 20 with 3 discusses 24 and 4 the 5 impact 5 impact 6 of 6 of 16 and 7 an 9 environment 8 impoverished 9 environment 9 environment 10 on 9 environment 16 and 10 on 11 cognition 11 cognition 12 in 12 in 15 studies 13 animal 15 studies 14 experimental 15 studies 16 and 19 studies 17 human 19 studies 18 experimental 19 studies 20 with 23 dwelling 21 community 23 dwelling 24 and 25 institutionalized 25 institutionalized 27 people 26 older 27 people results show that the cognitive functioning of old rats is more affected by an impoverished environment than young rats . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 show 0 ###LEFT-WALL### 20 . 1 results 2 show 2 show 3 that 3 that 6 functioning 3 that 12 affected 4 the 6 functioning 5 cognitive 6 functioning 6 functioning 7 of 6 functioning 10 is 7 of 9 rats 8 old 9 rats 10 is 11 more 10 is 12 affected 12 affected 13 by 12 affected 17 than 12 affected 19 rats 13 by 16 environment 14 an 16 environment 15 impoverished 16 environment 17 than 18 young similarly , sedentary and lonely people ( impoverished [environment] ) have worse cognitive functioning and show a faster cognitive [decline] than physically and socially active people . 0 ###LEFT-WALL### 6 people 0 ###LEFT-WALL### 15 and 0 ###LEFT-WALL### 27 . 1 similarly 2 , 1 similarly 6 people 3 sedentary 4 and 4 and 5 lonely 4 and 6 people 6 people 8 impoverished 6 people 15 and 7 ( 8 impoverished 8 impoverished 10 ) 11 have 14 functioning 11 have 15 and 12 worse 14 functioning 13 cognitive 14 functioning 15 and 16 show 16 show 26 people 17 a 26 people 18 faster 26 people 19 cognitive 21 than 19 cognitive 22 physically 19 cognitive 23 and 23 and 25 active 23 and 26 people 24 socially 25 active institutionalization further aggravates cognitive [decline] , probably due to the impoverished environment of nursing homes . 0 ###LEFT-WALL### 1 institutionalization 0 ###LEFT-WALL### 3 aggravates 0 ###LEFT-WALL### 16 . 1 institutionalization 3 aggravates 2 further 3 aggravates 3 aggravates 6 , 3 aggravates 15 homes 4 cognitive 6 , 6 , 7 probably 6 , 8 due 8 due 9 to 9 to 12 environment 10 the 12 environment 11 impoverished 12 environment 12 environment 13 of 13 of 14 nursing in institutions , residents spend an unnecessary and excessive amount of time in bed [;] out of bed they show mainly sedentary or completely passive behavior . 0 ###LEFT-WALL### 4 residents 0 ###LEFT-WALL### 5 spend 0 ###LEFT-WALL### 27 . 1 in 2 institutions 1 in 3 , 1 in 4 residents 4 residents 5 spend 5 spend 10 amount 6 an 10 amount 7 unnecessary 8 and 8 and 9 excessive 8 and 10 amount 10 amount 11 of 11 of 12 time 12 time 14 bed 12 time 18 bed 12 time 19 they 12 time 20 show 13 in 14 bed 16 out 17 of 17 of 18 bed 19 they 20 show 20 show 21 mainly 20 show 26 behavior 21 mainly 23 or 22 sedentary 23 or 23 or 25 passive 24 completely 25 passive in conclusion , older people , especially those that have been institutionalized , have poor levels of physical and social activity , which in turn has a negative impact on cognitive functioning . 0 ###LEFT-WALL### 2 conclusion 0 ###LEFT-WALL### 3 , 0 ###LEFT-WALL### 33 . 1 in 2 conclusion 3 , 5 people 3 , 14 have 3 , 22 , 4 older 5 people 5 people 8 those 5 people 14 have 6 , 7 especially 6 , 8 those 8 those 9 that 8 those 10 have 8 those 13 , 9 that 10 have 10 have 11 been 11 been 12 institutionalized 14 have 16 levels 15 poor 16 levels 16 levels 17 of 17 of 21 activity 18 physical 19 and 19 and 20 social 19 and 21 activity 22 , 23 which 22 , 26 has 23 which 26 has 24 in 25 turn 25 turn 26 has 26 has 29 impact 26 has 30 on 27 a 29 impact 28 negative 29 impact 30 on 32 functioning 31 cognitive 32 functioning [none] none the recession temporarily eased the health care workforce shortage , but our aging population will boost both retirements and demand for your services . 0 ###LEFT-WALL### 4 recession 0 ###LEFT-WALL### 6 eased 0 ###LEFT-WALL### 13 but 0 ###LEFT-WALL### 26 . 2 none 3 the 3 the 4 recession 4 recession 6 eased 5 temporarily 6 eased 6 eased 11 shortage 7 the 11 shortage 8 health 9 care 9 care 11 shortage 10 workforce 11 shortage 12 , 13 but 13 but 16 population 13 but 21 and 14 our 16 population 15 aging 16 population 16 population 17 will 17 will 21 and 18 boost 20 retirements 18 boost 21 and 19 both 20 retirements 21 and 22 demand 21 and 23 for 23 for 25 services 24 your 25 services here are tips for hiring and keeping staff . 0 ###LEFT-WALL### 1 here 0 ###LEFT-WALL### 2 are 0 ###LEFT-WALL### 9 . 1 here 2 are 2 are 3 tips 3 tips 4 for 4 for 6 and 5 hiring 6 and 6 and 8 staff 7 keeping 8 staff sleep - disordered breathing ( sdb ) is associated with a range of manifestations of cardiovascular disease such as stroke [,] ischemic heart disease and heart failure , and it is known to cause excessive daytime somnolence and be associated with traffic accidents . 0 ###LEFT-WALL### 1 sleep 0 ###LEFT-WALL### 9 associated 0 ###LEFT-WALL### 29 and 0 ###LEFT-WALL### 44 . 1 sleep 4 breathing 1 sleep 8 is 2 - 4 breathing 3 disordered 4 breathing 4 breathing 6 sdb 4 breathing 7 ) 5 ( 6 sdb 6 sdb 7 ) 8 is 9 associated 9 associated 10 with 9 associated 19 as 10 with 12 range 11 a 12 range 12 range 13 of 12 range 15 of 13 of 14 manifestations 15 of 17 disease 16 cardiovascular 17 disease 18 such 19 as 19 as 25 and 20 stroke 24 disease 22 ischemic 23 heart 23 heart 24 disease 24 disease 25 and 25 and 27 failure 26 heart 27 failure 28 , 29 and 29 and 30 it 29 and 32 known 30 it 31 is 31 is 32 known 32 known 33 to 32 known 38 and 33 to 38 and 34 cause 37 somnolence 34 cause 38 and 35 excessive 37 somnolence 36 daytime 37 somnolence 38 and 39 be 39 be 40 associated 40 associated 41 with 41 with 43 accidents 42 traffic 43 accidents therefore , it is important to detect sdb in the early stages . 0 ###LEFT-WALL### 3 it 0 ###LEFT-WALL### 4 is 0 ###LEFT-WALL### 13 . 1 therefore 2 , 1 therefore 3 it 3 it 4 is 4 is 5 important 5 important 6 to 5 important 7 detect 6 to 7 detect 7 detect 8 sdb 7 detect 9 in 9 in 12 stages 10 the 12 stages 11 early 12 stages we investigated the prevalence of sdb using a portable monitoring system in 81 commercial drivers . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 investigated 0 ###LEFT-WALL### 16 . 1 we 2 investigated 2 investigated 4 prevalence 2 investigated 7 using 3 the 4 prevalence 4 prevalence 5 of 5 of 6 sdb 7 using 11 system 7 using 12 in 8 a 9 portable 8 a 11 system 9 portable 11 system 10 monitoring 11 system 12 in 15 drivers 13 81 15 drivers 14 commercial 15 drivers we then analyzed predictive factors for sdb using their health examination records of the same fiscal year . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 analyzed 0 ###LEFT-WALL### 18 . 1 we 3 analyzed 2 then 3 analyzed 3 analyzed 5 factors 3 analyzed 8 using 4 predictive 5 factors 5 factors 6 for 6 for 7 sdb 8 using 12 records 9 their 12 records 10 health 12 records 11 examination 12 records 12 records 13 of 13 of 17 year 14 the 15 same 15 same 17 year 16 fiscal 17 year the prevalence of moderate [to] severe levels of sdb reached 28.3 % in all subjects . 0 ###LEFT-WALL### 2 prevalence 0 ###LEFT-WALL### 10 reached 0 ###LEFT-WALL### 16 . 1 the 2 prevalence 2 prevalence 3 of 2 prevalence 10 reached 3 of 7 levels 4 moderate 7 levels 6 severe 7 levels 7 levels 8 of 8 of 9 sdb 10 reached 12 % 10 reached 13 in 11 28.3 12 % 13 in 15 subjects 14 all 15 subjects multivariate analysis showed that the predictive factors which significantly correlated with sdb were : presence of glucose metabolism disorders ( odds [ratio] [ or []] 6.745 ) , weight [gain] greater than 10 kg from age 20 ( or 5.374 ) , and aging ( or 1.136 ) . 0 ###LEFT-WALL### 1 multivariate 0 ###LEFT-WALL### 14 : 0 ###LEFT-WALL### 49 . 1 multivariate 2 analysis 1 multivariate 13 were 1 multivariate 14 : 2 analysis 3 showed 3 showed 4 that 3 showed 7 factors 3 showed 13 were 5 the 7 factors 6 predictive 7 factors 7 factors 8 which 7 factors 10 correlated 7 factors 13 were 8 which 10 correlated 9 significantly 10 correlated 10 correlated 11 with 11 with 12 sdb 14 : 43 and 15 presence 16 of 15 presence 43 and 16 of 19 disorders 17 glucose 19 disorders 18 metabolism 19 disorders 19 disorders 21 odds 19 disorders 29 weight 20 ( 21 odds 21 odds 24 or 21 odds 28 , 23 [ 24 or 24 or 26 6.745 24 or 27 ) 28 , 29 weight 29 weight 35 from 29 weight 42 , 31 greater 32 than 32 than 33 10 33 10 34 kg 34 kg 35 from 35 from 36 age 36 age 37 20 36 age 39 or 38 ( 39 or 39 or 40 5.374 39 or 41 ) 43 and 44 aging 43 and 46 or 45 ( 46 or 46 or 47 1.136 46 or 48 ) these results suggest that health examination records could help detect a high - risk group of sdb , which is important because its early diagnosis could prevent commercial driver traffic accidents . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 suggest 0 ###LEFT-WALL### 18 , 0 ###LEFT-WALL### 32 . 1 these 2 results 2 results 3 suggest 3 suggest 4 that 4 that 6 examination 4 that 10 detect 5 health 6 examination 6 examination 7 records 6 examination 9 help 7 records 8 could 8 could 9 help 10 detect 15 group 11 a 12 high 11 a 15 group 12 high 13 - 12 high 15 group 14 risk 15 group 15 group 16 of 16 of 17 sdb 18 , 19 which 18 , 20 is 19 which 20 is 20 is 21 important 21 important 22 because 22 because 25 diagnosis 22 because 27 prevent 23 its 25 diagnosis 24 early 25 diagnosis 25 diagnosis 26 could 26 could 27 prevent 27 prevent 31 accidents 28 commercial 31 accidents 29 driver 31 accidents 30 traffic 31 accidents multiple trauma in the elderly is increasing with the aging population . 0 ###LEFT-WALL### 2 trauma 0 ###LEFT-WALL### 6 is 0 ###LEFT-WALL### 12 . 1 multiple 2 trauma 2 trauma 3 in 2 trauma 6 is 3 in 5 elderly 4 the 5 elderly 6 is 7 increasing 7 increasing 8 with 8 with 11 population 9 the 11 population 10 aging 11 population in contrast to their younger counterparts , elderly patients experience significantly higher mortality rates and complications after major trauma . 0 ###LEFT-WALL### 9 patients 0 ###LEFT-WALL### 10 experience 0 ###LEFT-WALL### 20 . 1 in 2 contrast 1 in 7 , 1 in 9 patients 2 contrast 3 to 3 to 6 counterparts 4 their 6 counterparts 5 younger 6 counterparts 8 elderly 9 patients 9 patients 10 experience 10 experience 15 and 10 experience 17 after 11 significantly 12 higher 12 higher 13 mortality 13 mortality 14 rates 14 rates 15 and 15 and 16 complications 17 after 19 trauma 18 major 19 trauma diminished physiological reserve and the existence of multiple medical comorbidities present additional challenges to management . 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 11 present 0 ###LEFT-WALL### 16 . 1 diminished 3 reserve 2 physiological 3 reserve 3 reserve 4 and 4 and 6 existence 4 and 7 of 4 and 11 present 5 the 6 existence 7 of 10 comorbidities 8 multiple 10 comorbidities 9 medical 10 comorbidities 11 present 13 challenges 11 present 14 to 12 additional 13 challenges 14 to 15 management [as] such [,] a different approach is required to care for the elderly trauma patient . 0 ###LEFT-WALL### 6 approach 0 ###LEFT-WALL### 8 required 0 ###LEFT-WALL### 16 . 2 such 4 a 4 a 6 approach 5 different 6 approach 6 approach 7 is 7 is 8 required 8 required 9 to 8 required 10 care 9 to 10 care 10 care 11 for 11 for 15 patient 12 the 15 patient 13 elderly 14 trauma 14 trauma 15 patient purpose : we describe the recruitment strategies and personnel and materials costs associated with two community - based research studies in a mexican - origin population . 0 ###LEFT-WALL### 1 purpose 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 27 . 2 : 3 we 2 : 4 describe 2 : 24 - 3 we 4 describe 4 describe 8 and 5 the 7 strategies 6 recruitment 7 strategies 7 strategies 8 and 8 and 16 community 8 and 20 studies 9 personnel 10 and 10 and 12 costs 10 and 13 associated 10 and 16 community 11 materials 12 costs 13 associated 14 with 14 with 15 two 17 - 20 studies 18 based 19 research 19 research 20 studies 20 studies 21 in 20 studies 24 - 21 in 23 mexican 22 a 23 mexican 24 - 26 population 25 origin 26 population we also highlight the role that academic - community partnerships played in the outreach and recruitment process for our studies . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 highlight 0 ###LEFT-WALL### 21 . 1 we 3 highlight 2 also 3 highlight 3 highlight 10 partnerships 3 highlight 12 in 3 highlight 18 for 4 the 10 partnerships 5 role 9 community 6 that 7 academic 7 academic 8 - 7 academic 9 community 9 community 10 partnerships 10 partnerships 11 played 12 in 15 and 13 the 14 outreach 14 outreach 15 and 15 and 17 process 16 recruitment 17 process 18 for 20 studies 19 our 20 studies we reviewed study documents using case study methodology to categorize recruitment methods , examine community partnerships , and calculate study costs . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 13 , 0 ###LEFT-WALL### 22 . 1 we 13 , 2 reviewed 4 documents 2 reviewed 13 , 3 study 4 documents 4 documents 5 using 5 using 8 methodology 5 using 9 to 5 using 10 categorize 6 case 8 methodology 7 study 8 methodology 9 to 10 categorize 10 categorize 12 methods 11 recruitment 12 methods 13 , 18 and 14 examine 16 partnerships 14 examine 18 and 15 community 16 partnerships 17 , 18 and 18 and 19 calculate 19 calculate 21 costs 20 study 21 costs results : we employed several recruitment methods to identify and solicit 154 female caregivers for participation in qualitative interviews and quantitative surveys . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 23 . 2 : 3 we 2 : 10 and 3 we 10 and 4 employed 7 methods 4 employed 10 and 5 several 7 methods 6 recruitment 7 methods 7 methods 8 to 7 methods 9 identify 8 to 9 identify 10 and 11 solicit 10 and 15 for 10 and 17 in 11 solicit 14 caregivers 12 154 13 female 13 female 14 caregivers 15 for 16 participation 17 in 20 and 18 qualitative 19 interviews 19 interviews 20 and 20 and 22 surveys 21 quantitative 22 surveys recruitment approaches included using flyers and word of mouth , attending health fairs , and partnering [with] nonprofit community - based organizations ( cbos ) to sponsor targeted recruitment events . 0 ###LEFT-WALL### 15 and 0 ###LEFT-WALL### 21 based 0 ###LEFT-WALL### 31 . 1 recruitment 2 approaches 2 approaches 3 included 2 approaches 6 and 3 included 4 using 4 using 5 flyers 6 and 9 mouth 6 and 11 attending 6 and 15 and 7 word 8 of 8 of 9 mouth 10 , 11 attending 11 attending 13 fairs 11 attending 14 , 12 health 13 fairs 14 , 15 and 15 and 19 community 15 and 20 - 15 and 21 based 16 partnering 19 community 18 nonprofit 19 community 21 based 22 organizations 21 based 26 to 22 organizations 24 cbos 23 ( 24 cbos 24 cbos 25 ) 26 to 30 events 27 sponsor 30 events 28 targeted 29 recruitment 29 recruitment 30 events face - to [-] face contact with community residents and partnerships with cbos were most effective in enrolling caregivers into the studies . 0 ###LEFT-WALL### 1 face 0 ###LEFT-WALL### 2 - 0 ###LEFT-WALL### 23 . 2 - 3 to 2 - 5 face 2 - 10 and 3 to 5 face 5 face 6 contact 5 face 7 with 7 with 9 residents 8 community 9 residents 10 and 11 partnerships 10 and 14 were 11 partnerships 12 with 11 partnerships 14 were 12 with 13 cbos 14 were 16 effective 15 most 16 effective 16 effective 17 in 17 in 18 enrolling 18 enrolling 19 caregivers 18 enrolling 20 into 20 into 22 studies 21 the 22 studies almost 70 % of participants attended a recruitment event sponsored or supported by cbos . 0 ###LEFT-WALL### 3 % 0 ###LEFT-WALL### 11 or 0 ###LEFT-WALL### 15 . 1 almost 2 70 2 70 3 % 3 % 4 of 3 % 11 or 4 of 5 participants 6 attended 9 event 6 attended 11 or 7 a 9 event 8 recruitment 9 event 9 event 10 sponsored 11 or 12 supported 11 or 13 by 13 by 14 cbos the least effective recruitment strategy was the use of flyers , which resulted in only 7 completed interviews or questionnaires . 0 ###LEFT-WALL### 5 strategy 0 ###LEFT-WALL### 6 was 0 ###LEFT-WALL### 11 , 0 ###LEFT-WALL### 21 . 1 the 5 strategy 2 least 3 effective 3 effective 4 recruitment 4 recruitment 5 strategy 5 strategy 6 was 6 was 8 use 7 the 8 use 8 use 9 of 9 of 10 flyers 11 , 12 which 11 , 13 resulted 12 which 13 resulted 13 resulted 14 in 14 in 19 or 15 only 16 7 16 7 18 interviews 17 completed 18 interviews 18 interviews 19 or 19 or 20 questionnaires time and costs related to carrying out the research varied by study , where personal interviews cost more on a [per] [-] participant basis ( $ 1,081 ) than the questionnaires ( $ 298 ) . 0 ###LEFT-WALL### 4 related 1 time 2 and 2 and 3 costs 2 and 4 related 4 related 5 to 4 related 11 by 4 related 36 . 5 to 6 carrying 6 carrying 7 out 6 carrying 9 research 8 the 9 research 9 research 10 varied 11 by 12 study 12 study 14 where 13 , 14 where 14 where 16 interviews 14 where 17 cost 14 where 35 ) 15 personal 16 interviews 16 interviews 17 cost 17 cost 18 more 17 cost 19 on 17 cost 29 than 19 on 24 basis 20 a 24 basis 23 participant 24 basis 24 basis 26 $ 25 ( 26 $ 26 $ 27 1,081 26 $ 28 ) 29 than 31 questionnaires 30 the 31 questionnaires 31 questionnaires 33 $ 32 ( 33 $ 33 $ 34 298 33 $ 35 ) however , almost the same amount of time was spent in the community for both studies . 0 ###LEFT-WALL### 6 amount 0 ###LEFT-WALL### 10 spent 0 ###LEFT-WALL### 17 . 1 however 2 , 1 however 6 amount 3 almost 5 same 4 the 5 same 5 same 6 amount 6 amount 7 of 6 amount 9 was 7 of 8 time 9 was 10 spent 10 spent 11 in 11 in 13 community 12 the 13 community 13 community 14 for 14 for 16 studies 15 both 16 studies implications : partnerships with cbos were critical for reaching the target enrollment for our studies . 0 ###LEFT-WALL### 1 implications 0 ###LEFT-WALL### 2 : 2 : 3 partnerships 2 : 6 were 2 : 16 . 3 partnerships 4 with 3 partnerships 6 were 4 with 5 cbos 6 were 7 critical 7 critical 8 for 8 for 9 reaching 9 reaching 12 enrollment 10 the 12 enrollment 11 target 12 enrollment 12 enrollment 13 for 13 for 15 studies 14 our 15 studies the relationship between the university of california - los angeles ( ucla ) resource center for minority aging research/center for health improvement for minority elderly and the department of aging provided the infrastructure for maintaining connections with academic - community partnerships . 0 ###LEFT-WALL### 26 and 0 ###LEFT-WALL### 31 provided 0 ###LEFT-WALL### 42 . 1 the 2 relationship 2 relationship 3 between 2 relationship 26 and 3 between 15 center 4 the 15 center 5 university 6 of 5 university 14 resource 6 of 7 california 7 california 10 angeles 8 - 10 angeles 9 los 10 angeles 10 angeles 12 ucla 10 angeles 13 ) 11 ( 12 ucla 12 ucla 13 ) 14 resource 15 center 15 center 16 for 15 center 20 for 15 center 23 for 16 for 19 research/center 17 minority 18 aging 18 aging 19 research/center 20 for 22 improvement 21 health 22 improvement 23 for 25 elderly 24 minority 25 elderly 26 and 28 department 26 and 29 of 26 and 31 provided 27 the 28 department 29 of 30 aging 31 provided 33 infrastructure 31 provided 34 for 32 the 33 infrastructure 34 for 35 maintaining 35 maintaining 36 connections 35 maintaining 37 with 37 with 41 partnerships 38 academic 39 - 38 academic 40 community 40 community 41 partnerships nevertheless , building partnerships required time , effort , and resources for both researchers and local organizations . 0 ###LEFT-WALL### 3 building 0 ###LEFT-WALL### 5 required 0 ###LEFT-WALL### 7 , 0 ###LEFT-WALL### 18 . 1 nevertheless 2 , 1 nevertheless 3 building 3 building 4 partnerships 3 building 5 required 5 required 6 time 7 , 10 and 8 effort 10 and 9 , 10 and 10 and 11 resources 10 and 12 for 12 for 15 and 13 both 14 researchers 14 researchers 15 and 15 and 17 organizations 16 local 17 organizations design : within geographic areas comprising our target population , 4 community organizations provided local space for conducting the study and program . 0 ###LEFT-WALL### 1 design 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 10 , 0 ###LEFT-WALL### 23 . 1 design 2 : 2 : 3 within 2 : 6 comprising 3 within 5 areas 4 geographic 5 areas 6 comprising 9 population 7 our 9 population 8 target 9 population 10 , 13 organizations 10 , 14 provided 11 4 13 organizations 12 community 13 organizations 13 organizations 14 provided 14 provided 16 space 15 local 16 space 16 space 17 for 17 for 18 conducting 18 conducting 21 and 19 the 20 study 20 study 21 and 21 and 22 program phase [i] - outreach in venues surrounding these organizations - included diabetes education , a short diabetes risk appraisal ( dra ) , and diabetes risk screening based on a fasting fingerstick glucose test . 0 ###LEFT-WALL### 1 phase 0 ###LEFT-WALL### 3 - 3 - 24 and 3 - 26 risk 3 - 35 . 4 outreach 5 in 4 outreach 24 and 5 in 6 venues 6 venues 7 surrounding 6 venues 13 education 6 venues 19 appraisal 7 surrounding 9 organizations 8 these 9 organizations 10 - 13 education 11 included 12 diabetes 12 diabetes 13 education 13 education 14 , 14 , 19 appraisal 15 a 16 short 15 a 19 appraisal 16 short 17 diabetes 17 diabetes 19 appraisal 18 risk 19 appraisal 19 appraisal 21 dra 19 appraisal 22 ) 20 ( 21 dra 21 dra 22 ) 23 , 24 and 24 and 25 diabetes 24 and 26 risk 26 risk 27 screening 27 screening 28 based 27 screening 29 on 29 on 34 test 30 a 34 test 31 fasting 34 test 32 fingerstick 34 test 33 glucose 34 test phase ii - trial recruitment - began concurrently for those found to be at risk of developing diabetes in phase i by explaining the study , lifestyle [program] , and research process . 0 ###LEFT-WALL### 1 phase 0 ###LEFT-WALL### 3 - 1 phase 2 ii 3 - 5 recruitment 3 - 6 - 4 trial 5 recruitment 6 - 30 and 6 - 33 . 7 began 8 concurrently 7 began 9 for 7 began 12 to 7 began 13 be 7 began 30 and 9 for 10 those 10 those 11 found 12 to 13 be 13 be 14 at 13 be 19 in 13 be 22 by 14 at 15 risk 15 risk 16 of 16 of 17 developing 17 developing 18 diabetes 19 in 20 phase 20 phase 21 i 22 by 23 explaining 23 explaining 25 study 24 the 25 study 25 study 27 lifestyle 26 , 27 lifestyle 27 lifestyle 29 , 30 and 31 research 31 research 32 process those interested and eligible enrolled in the 1 - year study . results : over 2 years , approximately 5,110 individuals received diabetes education , 1,917 completed a dra , and 1,164 [were] screened of which 641 ( 55 % ) had an elevated fingerstick result of ≥ 106 mg/dl . 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 5 enrolled 0 ###LEFT-WALL### 9 - 1 those 2 interested 1 those 3 and 3 and 4 eligible 3 and 5 enrolled 5 enrolled 6 in 6 in 8 1 7 the 8 1 9 - 11 study 9 - 12 . 9 - 51 . 10 year 11 study 12 . 13 results 12 . 14 : 14 : 17 years 14 : 18 , 15 over 16 2 16 2 17 years 18 , 21 individuals 18 , 22 received 18 , 25 , 19 approximately 21 individuals 20 5,110 21 individuals 21 individuals 22 received 22 received 24 education 23 diabetes 24 education 25 , 26 1,917 25 , 27 completed 25 , 31 and 26 1,917 27 completed 27 completed 29 dra 28 a 29 dra 30 , 31 and 31 and 32 1,164 31 and 48 ≥ 32 1,164 34 screened 32 1,164 35 of 32 1,164 37 641 32 1,164 47 of 32 1,164 48 ≥ 35 of 36 which 37 641 40 % 37 641 42 had 38 ( 40 % 39 55 40 % 40 % 41 ) 42 had 46 result 43 an 46 result 44 elevated 46 result 45 fingerstick 46 result 46 result 47 of 48 ≥ 50 mg/dl 49 106 50 mg/dl of the study sampling frame - persons over age 25 at risk of developing diabetes ( n = 544 ) - 238 ( 43 % ) enrolled in the trial ; of those who were study eligible ( n = 427 ) , 56 % enrolled . 0 ###LEFT-WALL### 7 persons 0 ###LEFT-WALL### 27 enrolled 0 ###LEFT-WALL### 31 ; 0 ###LEFT-WALL### 47 . 1 of 5 frame 1 of 6 - 1 of 7 persons 2 the 5 frame 3 study 5 frame 4 sampling 5 frame 7 persons 8 over 7 persons 13 of 7 persons 27 enrolled 8 over 9 age 9 age 10 25 9 age 11 at 11 at 12 risk 13 of 14 developing 14 developing 15 diabetes 15 diabetes 18 = 15 diabetes 22 238 16 ( 18 = 17 n 18 = 18 = 19 544 18 = 20 ) 21 - 22 238 22 238 25 % 22 238 26 ) 23 ( 25 % 24 43 25 % 25 % 26 ) 27 enrolled 28 in 28 in 30 trial 29 the 30 trial 31 ; 45 % 31 ; 46 enrolled 32 of 33 those 32 of 45 % 33 those 34 who 33 those 35 were 34 who 35 were 35 were 36 study 37 eligible 40 = 37 eligible 43 , 37 eligible 45 % 38 ( 40 = 39 n 40 = 40 = 41 427 40 = 42 ) 44 56 45 % 45 % 46 enrolled in the final sample , mean age was 56 years ( [sd] = 17 ) , 78 % were ethnic minorities , 32 % were spanish - speaking , and 15 % had a high school education or less . 0 ###LEFT-WALL### 7 age 0 ###LEFT-WALL### 8 was 0 ###LEFT-WALL### 16 , 0 ###LEFT-WALL### 40 . 1 in 4 sample 1 in 5 , 1 in 7 age 2 the 4 sample 3 final 4 sample 6 mean 7 age 7 age 8 was 8 was 10 years 9 56 10 years 10 years 14 17 11 ( 14 17 13 = 14 17 14 17 15 ) 16 , 18 % 16 , 19 were 16 , 22 , 17 78 18 % 18 % 19 were 19 were 21 minorities 20 ethnic 21 minorities 22 , 32 % 22 , 33 had 23 32 24 % 23 32 30 and 24 % 25 were 25 were 26 spanish 26 spanish 28 speaking 27 - 28 speaking 28 speaking 29 , 30 and 31 15 30 and 32 % 32 % 33 had 33 had 36 school 33 had 38 or 34 a 36 school 35 high 36 school 37 education 38 or 38 or 39 less implications : providing diabetes health education and screening prior to study [recruitment] may help overcome barriers to research participation in underserved communities , thus helping address difficulties recruiting minority and older populations into research , particularly research pertaining to chronic disease risk factors . 0 ###LEFT-WALL### 1 implications 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 7 and 0 ###LEFT-WALL### 15 overcome 1 implications 2 : 2 : 6 education 3 providing 5 health 4 diabetes 5 health 5 health 6 education 7 and 8 screening 7 and 14 help 8 screening 9 prior 8 screening 13 may 9 prior 10 to 9 prior 11 study 10 to 11 study 13 may 14 help 14 help 15 overcome 15 overcome 16 barriers 15 overcome 17 to 15 overcome 25 helping 17 to 18 research 18 research 19 participation 19 participation 20 in 20 in 22 communities 21 underserved 22 communities 23 , 24 thus 23 , 25 helping 25 helping 27 difficulties 25 helping 33 into 25 helping 44 . 26 address 27 difficulties 27 difficulties 28 recruiting 28 recruiting 30 and 28 recruiting 32 populations 29 minority 30 and 30 and 31 older 33 into 34 research 34 research 37 research 35 , 36 particularly 35 , 37 research 37 research 38 pertaining 37 research 44 . 38 pertaining 39 to 39 to 43 factors 40 chronic 41 disease 41 disease 43 factors 42 risk 43 factors the national institute on aging created the resource centers for minority aging research ( rcmars ) to address infrastructure development intended to reduce health disparities among older adults . 0 ###LEFT-WALL### 3 institute 0 ###LEFT-WALL### 6 created 0 ###LEFT-WALL### 29 . 1 the 3 institute 2 national 3 institute 3 institute 4 on 3 institute 6 created 4 on 5 aging 6 created 9 centers 7 the 9 centers 8 resource 9 centers 9 centers 10 for 9 centers 17 to 10 for 13 research 11 minority 12 aging 12 aging 13 research 13 research 15 rcmars 14 ( 15 rcmars 15 rcmars 16 ) 17 to 20 development 18 address 20 development 19 infrastructure 20 development 20 development 21 intended 21 intended 22 to 21 intended 26 among 22 to 23 reduce 23 reduce 25 disparities 24 health 25 disparities 26 among 28 adults 27 older 28 adults the overall goals of the rcmars are to [(] [a] [ )(increase the size of the cadre of researchers conducting research on issues related to minority aging [;] [(] [b] [ )(increase the diversity [of] researchers conducting research on minority aging [;] ( [c] [ )( and test reliable measures for use in older diverse populations [;] and [(] [d] [ )(conduct research on recruitment and retention of community - dwelling older adults for research addressing behavioral , social , and medical issues . 0 ###LEFT-WALL### 3 goals 0 ###LEFT-WALL### 7 are 1 the 3 goals 2 overall 3 goals 3 goals 4 of 3 goals 7 are 4 of 6 rcmars 5 the 6 rcmars 7 are 8 to 8 to 12 )(increase 12 )(increase 14 size 12 )(increase 24 related 13 the 14 size 14 size 15 of 14 size 24 related 15 of 17 cadre 16 the 17 cadre 17 cadre 18 of 18 of 19 researchers 19 researchers 20 conducting 20 conducting 21 research 21 research 22 on 22 on 23 issues 24 related 25 to 25 to 32 )(increase 26 minority 27 aging 27 aging 32 )(increase 32 )(increase 36 researchers 32 )(increase 38 research 33 the 36 researchers 34 diversity 36 researchers 36 researchers 37 conducting 36 researchers 38 research 38 research 39 on 39 on 47 and 40 minority 41 aging 40 minority 47 and 43 ( 47 and 47 and 50 measures 47 and 51 for 48 test 50 measures 49 reliable 50 measures 51 for 52 use 52 use 53 in 52 use 64 on 53 in 58 and 54 older 56 populations 55 diverse 56 populations 56 populations 58 and 58 and 63 research 62 )(conduct 63 research 64 on 66 and 65 recruitment 66 and 66 and 67 retention 66 and 68 of 66 and 73 adults 68 of 69 community 70 - 73 adults 71 dwelling 73 adults 72 older 73 adults 73 adults 74 for 73 adults 76 addressing 73 adults 84 . 74 for 75 research 76 addressing 83 issues 77 behavioral 78 , 77 behavioral 83 issues 79 social 81 and 80 , 81 and 81 and 82 medical 81 and 83 issues along with this latter goal , the rcmars developed and maintain academic - community partnerships . 0 ###LEFT-WALL### 8 rcmars 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 16 . 1 along 2 with 2 with 5 goal 2 with 6 , 2 with 8 rcmars 3 this 5 goal 4 latter 5 goal 7 the 8 rcmars 8 rcmars 10 and 9 developed 10 and 10 and 11 maintain 11 maintain 15 partnerships 12 academic 13 - 12 academic 14 community 14 community 15 partnerships to accomplish the recruitment and retention goal , the rcmars established community liaison working groups using a collaborative approach to scientific inquiry ; this special issue will identify research priorities for moving the science [of] recruitment and retention forward . 0 ###LEFT-WALL### 1 to 0 ###LEFT-WALL### 2 accomplish 0 ###LEFT-WALL### 8 , 0 ###LEFT-WALL### 40 . 1 to 2 accomplish 2 accomplish 5 and 3 the 4 recruitment 4 recruitment 5 and 5 and 7 goal 6 retention 7 goal 8 , 10 rcmars 8 , 11 established 8 , 23 ; 9 the 10 rcmars 10 rcmars 11 established 11 established 15 groups 11 established 16 using 11 established 20 to 12 community 13 liaison 13 liaison 14 working 14 working 15 groups 16 using 19 approach 17 a 18 collaborative 17 a 19 approach 18 collaborative 19 approach 20 to 22 inquiry 21 scientific 22 inquiry 23 ; 26 issue 23 ; 28 identify 24 this 26 issue 25 special 26 issue 26 issue 27 will 27 will 28 identify 28 identify 30 priorities 28 identify 31 for 29 research 30 priorities 31 for 32 moving 32 moving 37 and 33 the 36 recruitment 34 science 36 recruitment 36 recruitment 37 and 37 and 39 forward 38 retention 39 forward in addition , sustainable and efficient methods for fostering long - term partnerships will be identified between community and academia . 0 ###LEFT-WALL### 19 and 0 ###LEFT-WALL### 21 . 1 in 2 addition 2 addition 3 , 3 , 18 community 3 , 19 and 4 sustainable 5 and 5 and 7 methods 5 and 8 for 5 and 18 community 6 efficient 7 methods 8 for 9 fostering 9 fostering 13 partnerships 10 long 11 - 10 long 12 term 12 term 13 partnerships 13 partnerships 14 will 13 partnerships 17 between 14 will 15 be 15 be 16 identified 16 identified 17 between 19 and 20 academia evidence [-] based approaches to the recruitment and retention of diverse elders are explored . 0 ###LEFT-WALL### 4 approaches 0 ###LEFT-WALL### 14 explored 0 ###LEFT-WALL### 15 . 1 evidence 3 based 3 based 4 approaches 4 approaches 5 to 4 approaches 13 are 5 to 8 and 6 the 7 recruitment 7 recruitment 8 and 8 and 9 retention 8 and 10 of 10 of 12 elders 11 diverse 12 elders 13 are 14 explored we expect this supplement to serve as a catalyst for researchers interested in engaging diverse community [-] dwelling elders in health - related research . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 expect 0 ###LEFT-WALL### 22 - 0 ###LEFT-WALL### 25 . 1 we 2 expect 2 expect 4 supplement 3 this 4 supplement 4 supplement 5 to 4 supplement 12 interested 5 to 6 serve 6 serve 7 as 7 as 9 catalyst 7 as 12 interested 8 a 9 catalyst 9 catalyst 10 for 9 catalyst 12 interested 10 for 11 researchers 12 interested 13 in 13 in 14 engaging 14 engaging 19 elders 15 diverse 16 community 16 community 18 dwelling 18 dwelling 19 elders 19 elders 20 in 20 in 21 health 22 - 24 research 23 related 24 research in addition , this supplement should serve as a source of the most contemporary evidence - based approaches to the recruitment and retention of diverse older populations for participation in social , behavioral , and clinical research . 0 ###LEFT-WALL### 5 supplement 0 ###LEFT-WALL### 7 serve 0 ###LEFT-WALL### 16 - 0 ###LEFT-WALL### 38 . 1 in 2 addition 1 in 3 , 1 in 5 supplement 4 this 5 supplement 5 supplement 6 should 6 should 7 serve 7 serve 8 as 8 as 10 source 9 a 10 source 10 source 11 of 11 of 15 evidence 12 the 15 evidence 13 most 14 contemporary 14 contemporary 15 evidence 16 - 22 and 17 based 18 approaches 18 approaches 19 to 18 approaches 22 and 19 to 21 recruitment 20 the 21 recruitment 22 and 23 retention 22 and 24 of 24 of 27 populations 25 diverse 27 populations 26 older 27 populations 27 populations 28 for 27 populations 30 in 28 for 29 participation 30 in 37 research 31 social 32 , 31 social 37 research 33 behavioral 35 and 34 , 35 and 35 and 36 clinical 35 and 37 research purpose : to identify racial/ethnic differences in retention of older adults at 3 levels of participation in a prospective observational study : telephone , in [-] home assessments , and home visits followed by blood draws . 0 ###LEFT-WALL### 1 purpose 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 37 . 2 : 3 to 2 : 4 identify 2 : 22 : 3 to 4 identify 4 identify 6 differences 4 identify 7 in 5 racial/ethnic 6 differences 7 in 8 retention 8 retention 9 of 8 retention 12 at 9 of 11 adults 10 older 11 adults 12 at 14 levels 13 3 14 levels 14 levels 15 of 14 levels 17 in 15 of 16 participation 17 in 21 study 18 a 19 prospective 18 a 21 study 19 prospective 21 study 20 observational 21 study 22 : 30 and 23 telephone 25 in 23 telephone 30 and 24 , 25 in 25 in 28 assessments 25 in 29 , 27 home 28 assessments 30 and 31 home 31 home 32 visits 31 home 34 by 32 visits 33 followed 34 by 36 draws 35 blood 36 draws design and methods : a prospective study of 1,000 community - dwelling medicare beneficiaries aged 65 years and older included a baseline in [-] home assessment and telephone follow - up calls at 6 - month intervals [;] at 4 years , participants were asked to complete an additional in - home assessment and [have] blood drawn . 0 ###LEFT-WALL### 3 methods 0 ###LEFT-WALL### 4 : 1 design 2 and 2 and 3 methods 3 methods 4 : 4 : 13 medicare 5 a 6 prospective 5 a 13 medicare 6 prospective 7 study 7 study 8 of 7 study 12 dwelling 8 of 10 community 9 1,000 10 community 11 - 12 dwelling 13 medicare 14 beneficiaries 13 medicare 20 included 13 medicare 23 in 14 beneficiaries 15 aged 14 beneficiaries 20 included 15 aged 18 and 16 65 17 years 17 years 18 and 18 and 19 older 20 included 22 baseline 21 a 22 baseline 23 in 25 home 25 home 27 and 25 home 29 follow 26 assessment 27 and 27 and 28 telephone 27 and 29 follow 29 follow 35 - 30 - 35 - 31 up 32 calls 32 calls 33 at 32 calls 35 - 33 at 34 6 35 - 37 intervals 36 month 37 intervals 37 intervals 39 at 39 at 40 4 40 4 41 years 40 4 52 home 41 years 52 home 42 , 45 asked 43 participants 44 were 44 were 45 asked 45 asked 46 to 45 asked 51 - 45 asked 52 home 46 to 47 complete 47 complete 50 in 48 an 50 in 49 additional 50 in 52 home 54 and 53 assessment 54 and 54 and 56 blood 54 and 58 . 56 blood 57 drawn results : after 4 years , 21.7 % died and 0.7 % withdrew , leaving 776 participants eligible [for] follow - up [(] 49 % african american ; 46 % male ; 51 [%] [rural] [ )( 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 37 )( 2 : 10 and 2 : 20 follow 2 : 21 - 3 after 5 years 3 after 6 , 3 after 10 and 4 4 5 years 7 21.7 8 % 7 21.7 10 and 8 % 9 died 10 and 11 0.7 10 and 15 leaving 10 and 20 follow 11 0.7 12 % 12 % 13 withdrew 13 withdrew 14 , 15 leaving 17 participants 15 leaving 18 eligible 16 776 17 participants 21 - 27 american 21 - 28 ; 21 - 32 ; 22 up 27 american 24 49 25 % 25 % 26 african 26 african 27 american 28 ; 31 male 29 46 31 male 30 % 31 male 32 ; 33 51 retention for [telephone] [follow] - up was 94.5 % ( n = 733/776 ) ; 624/733 ( 85.1 % ) had home interviews , and 408/624 ( 65.4 % ) had a nurse come to the home for the blood draw . 0 ###LEFT-WALL### 1 retention 0 ###LEFT-WALL### 7 was 0 ###LEFT-WALL### 15 ; 0 ###LEFT-WALL### 34 come 0 ###LEFT-WALL### 42 . 1 retention 2 for 1 retention 7 was 2 for 6 up 5 - 6 up 7 was 9 % 8 94.5 9 % 9 % 12 = 10 ( 12 = 11 n 12 = 12 = 13 733/776 12 = 14 ) 15 ; 16 624/733 15 ; 21 had 15 ; 25 and 16 624/733 19 % 16 624/733 21 had 17 ( 19 % 18 85.1 19 % 19 % 20 ) 21 had 23 interviews 22 home 23 interviews 24 , 25 and 25 and 26 408/624 25 and 31 had 26 408/624 29 % 26 408/624 31 had 27 ( 29 % 28 65.4 29 % 29 % 30 ) 31 had 33 nurse 31 had 34 come 32 a 33 nurse 34 come 35 to 35 to 37 home 36 the 37 home 37 home 38 for 38 for 41 draw 39 the 41 draw 40 blood 41 draw african american race was an independent predictor of participation [in] [in] - home assessments , but african american race and rural residence were independent predictors of not participating in a blood draw . 0 ###LEFT-WALL### 3 race 0 ###LEFT-WALL### 4 was 0 ###LEFT-WALL### 16 but 0 ###LEFT-WALL### 33 . 1 african 3 race 2 american 3 race 3 race 4 was 4 was 7 predictor 5 an 6 independent 5 an 7 predictor 6 independent 7 predictor 7 predictor 8 of 8 of 9 participation 9 participation 14 assessments 12 - 14 assessments 13 home 14 assessments 14 assessments 15 , 16 but 20 and 16 but 23 were 17 african 19 race 18 american 19 race 19 race 20 and 20 and 22 residence 20 and 23 were 21 rural 22 residence 23 were 25 predictors 24 independent 25 predictors 25 predictors 26 of 26 of 27 not 27 not 28 participating 28 participating 29 in 29 in 32 draw 30 a 32 draw 31 blood 32 draw implications : recruitment efforts designed to demonstrate respect for all research participants , home visits , and telephone follow - up interviews facilitate high retention rates for both african american and white older adults ; however , additional efforts are required to enhance participation of african american and rural participants in research requiring blood draws . 0 ###LEFT-WALL### 1 implications 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 13 , 1 implications 2 : 2 : 4 efforts 3 recruitment 4 efforts 4 efforts 5 designed 4 efforts 6 to 4 efforts 7 demonstrate 4 efforts 9 for 6 to 7 demonstrate 7 demonstrate 8 respect 9 for 12 participants 10 all 12 participants 11 research 12 participants 13 , 17 and 13 , 19 follow 13 , 20 - 14 home 15 visits 15 visits 17 and 16 , 17 and 17 and 18 telephone 17 and 19 follow 20 - 22 interviews 20 - 23 facilitate 20 - 35 ; 20 - 43 enhance 20 - 56 . 21 up 22 interviews 22 interviews 23 facilitate 23 facilitate 26 rates 24 high 26 rates 25 retention 26 rates 26 rates 27 for 27 for 34 adults 28 both 34 adults 29 african 34 adults 30 american 31 and 31 and 32 white 31 and 34 adults 33 older 34 adults 35 ; 39 efforts 35 ; 41 required 36 however 37 , 36 however 39 efforts 38 additional 39 efforts 39 efforts 40 are 40 are 41 required 41 required 42 to 42 to 43 enhance 43 enhance 44 participation 43 enhance 51 in 44 participation 45 of 45 of 50 participants 46 african 50 participants 47 american 48 and 48 and 49 rural 48 and 50 participants 51 in 52 research 52 research 53 requiring 53 requiring 54 blood 53 requiring 55 draws 54 blood 55 draws purpose of the study : investigating health disparities requires studies designed to recruit and retain racially and socioeconomically diverse cohorts . 0 ###LEFT-WALL### 4 study 0 ###LEFT-WALL### 5 : 1 purpose 2 of 2 of 3 the 3 the 4 study 5 : 6 investigating 5 : 9 requires 5 : 21 . 6 investigating 8 disparities 6 investigating 9 requires 7 health 8 disparities 9 requires 17 and 10 studies 11 designed 10 studies 17 and 11 designed 12 to 11 designed 14 and 12 to 14 and 13 recruit 14 and 14 and 15 retain 14 and 16 racially 17 and 20 cohorts 18 socioeconomically 19 diverse 19 diverse 20 cohorts it is critical to address the barriers that disproportionately affect participation in clinical research by minorities and [the] socioeconomically disadvantaged . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 21 . 1 it 2 is 2 is 3 critical 3 critical 4 to 4 to 5 address 5 address 7 barriers 6 the 7 barriers 7 barriers 8 that 7 barriers 17 and 8 that 17 and 9 disproportionately 10 affect 10 affect 11 participation 10 affect 12 in 10 affect 15 by 10 affect 17 and 12 in 14 research 13 clinical 14 research 15 by 16 minorities 17 and 20 disadvantaged 19 socioeconomically 20 disadvantaged this study sought to identify [and] [rectify] these barriers to recruit and retain a biracial [(] african american [and] [non] - hispanic white ) and socioeconomically diverse cohort for a longitudinal study . 0 ###LEFT-WALL### 25 and 0 ###LEFT-WALL### 33 . 1 this 2 study 2 study 3 sought 2 study 25 and 3 sought 4 to 4 to 5 identify 5 identify 9 barriers 5 identify 10 to 8 these 9 barriers 10 to 12 and 11 recruit 12 and 12 and 13 retain 13 retain 18 american 14 a 15 biracial 14 a 18 american 15 biracial 17 african 17 african 18 american 18 american 23 white 21 - 23 white 22 hispanic 23 white 23 white 24 ) 25 and 28 cohort 25 and 29 for 26 socioeconomically 27 diverse 27 diverse 28 cohort 29 for 32 study 30 a 31 longitudinal 30 a 32 study 31 longitudinal 32 study design and method : the healthy aging in neighborhoods of diversity across the life span study is [a] 20 - year longitudinal examination of how race and socioeconomic status influence the development of age - related health disparities . 0 ###LEFT-WALL### 3 method 0 ###LEFT-WALL### 4 : 1 design 2 and 2 and 3 method 4 : 7 aging 4 : 17 is 4 : 35 - 4 : 39 . 5 the 7 aging 6 healthy 7 aging 7 aging 8 in 7 aging 17 is 8 in 9 neighborhoods 9 neighborhoods 10 of 10 of 11 diversity 11 diversity 12 across 12 across 16 study 13 the 16 study 14 life 15 span 15 span 16 study 17 is 19 20 19 20 23 examination 20 - 23 examination 21 year 23 examination 22 longitudinal 23 examination 23 examination 24 of 23 examination 33 of 23 examination 35 - 24 of 25 how 25 how 27 and 25 how 30 influence 26 race 27 and 27 and 29 status 27 and 30 influence 28 socioeconomic 29 status 30 influence 32 development 31 the 32 development 33 of 34 age 35 - 38 disparities 36 related 37 health 37 health 38 disparities one goal was to create a multifactorial recruitment and retention strategy . 0 ###LEFT-WALL### 2 goal 0 ###LEFT-WALL### 12 . 1 one 2 goal 2 goal 3 was 3 was 4 to 3 was 5 create 4 to 5 create 5 create 9 and 6 a 7 multifactorial 6 a 8 recruitment 7 multifactorial 8 recruitment 8 recruitment 9 and 9 and 11 strategy 10 retention 11 strategy the recruitment paradigm targeted known barriers and identified those unique to the study 's urban environment . 0 ###LEFT-WALL### 3 paradigm 0 ###LEFT-WALL### 7 and 0 ###LEFT-WALL### 17 . 1 the 3 paradigm 2 recruitment 3 paradigm 3 paradigm 7 and 4 targeted 6 barriers 4 targeted 7 and 5 known 6 barriers 7 and 8 identified 8 identified 9 those 9 those 10 unique 10 unique 11 to 11 to 16 environment 12 the 13 study 13 study 14 's 14 's 16 environment 15 urban 16 environment the retention paradigm mirrored the recruitment plan but was based on specifically developed approaches . 0 ###LEFT-WALL### 3 paradigm 0 ###LEFT-WALL### 8 but 0 ###LEFT-WALL### 15 . 1 the 3 paradigm 2 retention 3 paradigm 3 paradigm 8 but 4 mirrored 7 plan 4 mirrored 8 but 5 the 7 plan 6 recruitment 7 plan 8 but 9 was 9 was 10 based 10 based 11 on 11 on 14 approaches 12 specifically 13 developed 13 developed 14 approaches results : this cohort recruitment required attention to developing community partnerships , designing the research study to meet the study hypotheses and to provide benefit to participants , providing a safe community - based [site] for the research and creating didactics to develop staff cultural proficiency . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 1 results 2 : 2 : 7 attention 2 : 13 designing 2 : 34 based 3 this 7 attention 4 cohort 5 recruitment 5 recruitment 7 attention 6 required 7 attention 7 attention 8 to 8 to 9 developing 9 developing 11 partnerships 10 community 11 partnerships 12 , 13 designing 13 designing 16 study 13 designing 17 to 13 designing 26 to 13 designing 33 - 14 the 16 study 15 research 16 study 17 to 22 and 18 meet 21 hypotheses 18 meet 22 and 19 the 21 hypotheses 20 study 21 hypotheses 22 and 23 to 22 and 25 benefit 23 to 24 provide 26 to 27 participants 27 participants 29 providing 28 , 29 providing 29 providing 32 community 29 providing 33 - 30 a 32 community 31 safe 32 community 33 - 34 based 34 based 36 for 34 based 47 . 36 for 39 and 37 the 38 research 38 research 39 and 39 and 40 creating 39 and 41 didactics 39 and 44 staff 41 didactics 42 to 41 didactics 43 develop 41 didactics 44 staff 42 to 43 develop 44 staff 46 proficiency 45 cultural 46 proficiency these efforts facilitated study implementation and enhanced recruitment resulting in [accrual] [of] a biracial and socioeconomically diverse cohort of 3,722 participants . 0 ###LEFT-WALL### 2 efforts 0 ###LEFT-WALL### 4 study 0 ###LEFT-WALL### 22 . 1 these 2 efforts 2 efforts 3 facilitated 2 efforts 4 study 4 study 6 and 4 study 10 in 5 implementation 6 and 6 and 8 recruitment 6 and 9 resulting 7 enhanced 8 recruitment 10 in 18 cohort 13 a 18 cohort 14 biracial 15 and 15 and 17 diverse 15 and 18 cohort 16 socioeconomically 17 diverse 18 cohort 19 of 19 of 21 participants 20 3,722 21 participants implications : recruiting and retaining minority or poor research participants is challenging but possible . 0 ###LEFT-WALL### 1 implications 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 15 . 1 implications 2 : 2 : 3 recruiting 4 and 5 retaining 4 and 11 is 5 retaining 7 or 5 retaining 11 is 6 minority 7 or 7 or 10 participants 8 poor 10 participants 9 research 10 participants 11 is 13 but 12 challenging 13 but 13 but 14 possible the essential facets include clear communication of the research hypothesis , focus on providing a direct benefit for participants , and selection of a hypothesis that is directly relevant to the community studied . 0 ###LEFT-WALL### 3 facets 0 ###LEFT-WALL### 4 include 0 ###LEFT-WALL### 11 , 0 ###LEFT-WALL### 34 . 1 the 3 facets 2 essential 3 facets 3 facets 4 include 4 include 6 communication 5 clear 6 communication 6 communication 7 of 7 of 10 hypothesis 8 the 10 hypothesis 9 research 10 hypothesis 11 , 12 focus 12 focus 13 on 12 focus 18 for 12 focus 30 to 13 on 14 providing 14 providing 17 benefit 15 a 17 benefit 16 direct 17 benefit 18 for 21 and 19 participants 21 and 20 , 21 and 21 and 22 selection 21 and 23 of 23 of 25 hypothesis 24 a 25 hypothesis 25 hypothesis 26 that 25 hypothesis 27 is 26 that 27 is 27 is 28 directly 27 is 29 relevant 30 to 32 community 31 the 32 community 32 community 33 studied we highlight several critical challenges that must be addressed to accelerate the advancement of the science on recruitment [and] retention of ethnically diverse older adults into health research . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 highlight 0 ###LEFT-WALL### 29 . 1 we 2 highlight 2 highlight 5 challenges 2 highlight 10 to 2 highlight 17 on 3 several 5 challenges 4 critical 5 challenges 5 challenges 6 that 5 challenges 7 must 6 that 7 must 7 must 8 be 8 be 9 addressed 10 to 11 accelerate 11 accelerate 13 advancement 12 the 13 advancement 13 advancement 14 of 14 of 16 science 15 the 16 science 17 on 20 retention 18 recruitment 20 retention 20 retention 21 of 20 retention 26 into 21 of 25 adults 22 ethnically 23 diverse 23 diverse 25 adults 24 older 25 adults 26 into 28 research 27 health 28 research these include the relative lack of attention by researchers to methodological issues related to recruitment [and] retention of ethnically diverse populations and the inadequacy of funding to advance systematically this field . 0 ###LEFT-WALL### 1 these 0 ###LEFT-WALL### 2 include 0 ###LEFT-WALL### 32 . 1 these 2 include 2 include 5 lack 2 include 10 to 3 the 5 lack 4 relative 5 lack 5 lack 6 of 5 lack 8 by 6 of 7 attention 8 by 9 researchers 10 to 22 and 11 methodological 12 issues 12 issues 13 related 12 issues 14 to 12 issues 22 and 14 to 17 retention 15 recruitment 17 retention 17 retention 18 of 18 of 21 populations 19 ethnically 20 diverse 20 diverse 21 populations 22 and 24 inadequacy 22 and 25 of 23 the 24 inadequacy 25 of 26 funding 26 funding 27 to 26 funding 31 field 27 to 28 advance 28 advance 29 systematically 30 this 31 field we describe strategies used by the resource centers on minority aging research and other national institute of aging - funded programs to advance the science of [recruitment] of ethnically diverse older adults . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 describe 0 ###LEFT-WALL### 19 - 0 ###LEFT-WALL### 33 . 1 we 2 describe 2 describe 3 strategies 2 describe 5 by 3 strategies 4 used 5 by 13 and 6 the 8 centers 7 resource 8 centers 8 centers 9 on 8 centers 13 and 9 on 12 research 10 minority 11 aging 11 aging 12 research 13 and 16 institute 13 and 17 of 14 other 16 institute 15 national 16 institute 17 of 18 aging 19 - 21 programs 20 funded 21 programs 21 programs 22 to 21 programs 26 of 21 programs 28 of 22 to 23 advance 23 advance 25 science 24 the 25 science 25 science 26 of 28 of 32 adults 29 ethnically 30 diverse 30 diverse 32 adults 31 older 32 adults finally , we propose a set of broad recommendations designed to generate a body of evidence on successful methods of recruitment [and] retention of ethnically diverse populations in health research . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 propose 0 ###LEFT-WALL### 31 . 1 finally 2 , 1 finally 3 we 3 we 4 propose 4 propose 6 set 4 propose 17 on 5 a 6 set 6 set 7 of 6 set 10 designed 7 of 9 recommendations 8 broad 9 recommendations 10 designed 11 to 10 designed 12 generate 11 to 12 generate 12 generate 14 body 13 a 14 body 14 body 15 of 15 of 16 evidence 17 on 19 methods 18 successful 19 methods 19 methods 20 of 19 methods 24 of 20 of 23 retention 21 recruitment 23 retention 24 of 27 populations 25 ethnically 26 diverse 26 diverse 27 populations 27 populations 28 in 28 in 30 research 29 health 30 research to eliminate health disparities and better understand aging processes in ethnically diverse populations , much more research is needed on effective strategies for increasing minority enrollment [in] health research . 0 ###LEFT-WALL### 1 to 0 ###LEFT-WALL### 5 and 0 ###LEFT-WALL### 14 , 0 ###LEFT-WALL### 30 . 1 to 5 and 2 eliminate 4 disparities 2 eliminate 5 and 3 health 4 disparities 5 and 7 understand 5 and 10 in 6 better 7 understand 7 understand 9 processes 8 aging 9 processes 10 in 13 populations 11 ethnically 12 diverse 12 diverse 13 populations 14 , 17 research 14 , 19 needed 15 much 16 more 16 more 17 research 17 research 18 is 18 is 19 needed 19 needed 20 on 20 on 22 strategies 21 effective 22 strategies 22 strategies 23 for 23 for 24 increasing 24 increasing 29 research 25 minority 26 enrollment 26 enrollment 29 research 28 health 29 research comparative effectiveness research on more intensive recruitment [and] retention methods , which are often needed for including diverse populations , will require dedicated funding and concerted efforts by investigators . 0 ###LEFT-WALL### 3 research 0 ###LEFT-WALL### 23 dedicated 0 ###LEFT-WALL### 30 . 1 comparative 3 research 2 effectiveness 3 research 3 research 4 on 3 research 23 dedicated 4 on 9 retention 5 more 9 retention 6 intensive 7 recruitment 7 recruitment 9 retention 9 retention 10 methods 9 retention 22 require 10 methods 12 which 10 methods 21 will 11 , 12 which 12 which 13 are 12 which 20 , 13 are 15 needed 14 often 15 needed 15 needed 16 for 16 for 17 including 17 including 19 populations 18 diverse 19 populations 21 will 22 require 23 dedicated 27 efforts 23 dedicated 28 by 24 funding 25 and 25 and 26 concerted 25 and 27 efforts 28 by 29 investigators purpose : to describe the results of efforts to recruit asian americans into longitudinal research on cognitive [decline] in aging . 0 ###LEFT-WALL### 1 purpose 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 21 . 1 purpose 2 : 2 : 3 to 2 : 17 cognitive 3 to 4 describe 4 describe 6 results 5 the 6 results 6 results 7 of 7 of 8 efforts 8 efforts 9 to 8 efforts 16 on 9 to 10 recruit 10 recruit 12 americans 10 recruit 13 into 10 recruit 16 on 11 asian 12 americans 13 into 15 research 14 longitudinal 15 research 17 cognitive 19 in 19 in 20 aging design and methods : recruitment strategies include clinics for assessment of cognitive impairment at the university of california , san francisco campus and san francisco 's chinatown , lectures to local health care providers and community members , participation in community events , and publications in mass media . 0 ###LEFT-WALL### 3 methods 0 ###LEFT-WALL### 4 : 0 ###LEFT-WALL### 49 . 1 design 2 and 2 and 3 methods 3 methods 4 : 4 : 8 clinics 4 : 14 at 5 recruitment 8 clinics 6 strategies 8 clinics 7 include 8 clinics 8 clinics 9 for 8 clinics 11 of 9 for 10 assessment 11 of 13 impairment 12 cognitive 13 impairment 14 at 23 and 15 the 16 university 16 university 17 of 16 university 19 , 17 of 18 california 19 , 22 campus 19 , 23 and 20 san 21 francisco 21 francisco 22 campus 23 and 24 san 23 and 25 francisco 23 and 29 lectures 25 francisco 28 , 26 's 27 chinatown 26 's 28 , 28 , 29 lectures 29 lectures 30 to 30 to 44 and 31 local 34 providers 32 health 33 care 33 care 34 providers 34 providers 35 and 35 and 37 members 35 and 39 participation 35 and 44 and 36 community 37 members 38 , 39 participation 39 participation 40 in 39 participation 43 , 40 in 42 events 41 community 42 events 43 , 44 and 44 and 45 publications 44 and 46 in 46 in 48 media 47 mass 48 media results : over 200 chinese patients were evaluated in our outreach clinic . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 6 patients 2 : 8 evaluated 2 : 13 . 3 over 4 200 4 200 6 patients 5 chinese 6 patients 6 patients 7 were 7 were 8 evaluated 8 evaluated 9 in 9 in 12 clinic 10 our 12 clinic 11 outreach 12 clinic many were primarily chinese speaking with low levels of education . 0 ###LEFT-WALL### 1 many 0 ###LEFT-WALL### 2 were 0 ###LEFT-WALL### 11 . 1 many 2 were 2 were 3 primarily 2 were 4 chinese 4 chinese 5 speaking 5 speaking 6 with 6 with 8 levels 7 low 8 levels 8 levels 9 of 9 of 10 education one hundred and twenty - five participants enrolled , and annual follow - up [has] [been] 88 % . 0 ###LEFT-WALL### 4 twenty 0 ###LEFT-WALL### 14 up 0 ###LEFT-WALL### 19 . 1 one 2 hundred 2 hundred 3 and 3 and 4 twenty 4 twenty 6 five 4 twenty 14 up 5 - 6 five 6 five 10 and 6 five 12 follow 6 five 13 - 7 participants 8 enrolled 7 participants 10 and 9 , 10 and 10 and 11 annual 10 and 12 follow 14 up 18 % 17 88 18 % among enrollees , 36 % were recruited from our clinical service ; 30 % via word of mouth [;] and the rest from community lectures and events , flyers , [and] mass media . 0 ###LEFT-WALL### 5 % 0 ###LEFT-WALL### 7 recruited 0 ###LEFT-WALL### 12 ; 0 ###LEFT-WALL### 34 . 1 among 2 enrollees 1 among 3 , 1 among 5 % 4 36 5 % 5 % 6 were 6 were 7 recruited 7 recruited 8 from 8 from 11 service 9 our 11 service 10 clinical 11 service 12 ; 14 % 12 ; 32 mass 13 30 14 % 14 % 15 via 14 % 23 from 14 % 32 mass 15 via 20 and 16 word 17 of 17 of 18 mouth 18 mouth 20 and 20 and 22 rest 21 the 22 rest 23 from 26 and 24 community 25 lectures 25 lectures 26 and 26 and 27 events 26 and 29 flyers 28 , 29 flyers 29 flyers 30 , 32 mass 33 media participants who enrolled were relatively highly educated , tended to be interested in learning about their cognitive abilities , and were supportive [of] the goals of research . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 20 and 0 ###LEFT-WALL### 28 . 1 participants 2 who 1 participants 3 enrolled 1 participants 20 and 2 who 3 enrolled 4 were 5 relatively 4 were 7 educated 4 were 20 and 6 highly 7 educated 7 educated 9 tended 8 , 9 tended 9 tended 10 to 9 tended 13 in 9 tended 15 about 9 tended 19 , 10 to 11 be 11 be 12 interested 13 in 14 learning 15 about 18 abilities 16 their 18 abilities 17 cognitive 18 abilities 19 , 20 and 20 and 21 were 20 and 25 goals 21 were 22 supportive 24 the 25 goals 25 goals 26 of 26 of 27 research implications : despite the significant cultural and linguistic barriers , chinese americans can be successfully recruited into longitudinal studies of aging and cognitive impairment . 0 ###LEFT-WALL### 1 implications 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 10 , 0 ###LEFT-WALL### 25 . 1 implications 2 : 2 : 3 despite 3 despite 9 barriers 4 the 9 barriers 5 significant 9 barriers 6 cultural 7 and 7 and 8 linguistic 7 and 9 barriers 10 , 12 americans 10 , 16 recruited 11 chinese 12 americans 12 americans 13 can 13 can 14 be 14 be 15 successfully 14 be 16 recruited 16 recruited 17 into 17 into 22 and 18 longitudinal 19 studies 19 studies 20 of 19 studies 22 and 20 of 21 aging 22 and 24 impairment 23 cognitive 24 impairment clinical services are a critical component of such an effort , and low education and other factors that may be associated with it are clear barriers to research participation . 0 ###LEFT-WALL### 2 services 0 ###LEFT-WALL### 3 are 0 ###LEFT-WALL### 11 , 0 ###LEFT-WALL### 30 . 1 clinical 2 services 2 services 3 are 3 are 6 component 4 a 6 component 5 critical 6 component 6 component 7 of 7 of 10 effort 8 such 9 an 9 an 10 effort 11 , 12 and 11 , 28 research 12 and 15 and 12 and 25 clear 13 low 14 education 14 education 15 and 15 and 17 factors 15 and 18 that 15 and 19 may 15 and 24 are 16 other 17 factors 18 that 19 may 19 may 20 be 20 be 21 associated 21 associated 22 with 22 with 23 it 24 are 25 clear 25 clear 26 barriers 25 clear 27 to 27 to 28 research 28 research 29 participation recruitment and retention of research participants is evolving with the changing demographics of the american population , in [particular] its growing diversity . 0 ###LEFT-WALL### 1 recruitment 0 ###LEFT-WALL### 2 and 2 and 3 retention 2 and 7 is 3 retention 4 of 3 retention 7 is 4 of 6 participants 5 research 6 participants 7 is 8 evolving 8 evolving 9 with 9 with 12 demographics 10 the 12 demographics 11 changing 12 demographics 12 demographics 13 of 13 of 16 population 14 the 16 population 15 american 16 population 16 population 18 in 17 , 18 in 18 in 22 diversity 18 in 23 . 20 its 22 diversity 21 growing 22 diversity the cultural - historical background and sociopolitical conditions of each diverse group poses unique challenges [in] developing successful recruitment and retention methods and strategies . 0 ###LEFT-WALL### 6 and 0 ###LEFT-WALL### 25 . 1 the 5 background 2 cultural 3 - 2 cultural 5 background 4 historical 5 background 5 background 6 and 6 and 8 conditions 7 sociopolitical 8 conditions 8 conditions 9 of 9 of 23 and 10 each 19 recruitment 11 diverse 19 recruitment 12 group 13 poses 13 poses 17 developing 14 unique 15 challenges 15 challenges 17 developing 17 developing 19 recruitment 18 successful 19 recruitment 19 recruitment 20 and 20 and 22 methods 20 and 23 and 21 retention 22 methods 23 and 24 strategies this critical collection of articles demonstrates important theoretical and conceptual frameworks that seek to address the shortcomings of previous models of recruiting diverse populations . 0 ###LEFT-WALL### 3 collection 0 ###LEFT-WALL### 6 demonstrates 0 ###LEFT-WALL### 25 . 1 this 3 collection 2 critical 3 collection 3 collection 4 of 3 collection 6 demonstrates 4 of 5 articles 6 demonstrates 11 frameworks 7 important 11 frameworks 8 theoretical 9 and 9 and 10 conceptual 9 and 11 frameworks 11 frameworks 12 that 11 frameworks 13 seek 12 that 13 seek 13 seek 14 to 13 seek 15 address 14 to 15 address 15 address 17 shortcomings 16 the 17 shortcomings 17 shortcomings 18 of 18 of 20 models 19 previous 20 models 20 models 21 of 21 of 22 recruiting 22 recruiting 24 populations 23 diverse 24 populations understanding the key components of cultural distinctions , such as values and beliefs , community cohesion , and collective history , has proven to be instrumental in reaching out to these diverse groups . 0 ###LEFT-WALL### 1 understanding 0 ###LEFT-WALL### 23 proven 0 ###LEFT-WALL### 34 . 1 understanding 4 components 1 understanding 10 as 1 understanding 22 has 2 the 4 components 3 key 4 components 4 components 5 of 5 of 7 distinctions 6 cultural 7 distinctions 8 , 10 as 9 such 10 as 10 as 18 and 10 as 21 , 11 values 12 and 12 and 13 beliefs 12 and 16 cohesion 12 and 18 and 14 , 16 cohesion 15 community 16 cohesion 16 cohesion 17 , 17 , 18 and 18 and 20 history 19 collective 20 history 22 has 23 proven 23 proven 24 to 23 proven 25 be 24 to 25 be 25 be 26 instrumental 26 instrumental 27 in 26 instrumental 30 to 27 in 28 reaching 28 reaching 29 out 30 to 33 groups 31 these 33 groups 32 diverse 33 groups this important strategy has allowed researchers to overcome the barriers that have been fostered in the past and has built the trust necessary to move forward into an inclusive approach to aging research . 0 ###LEFT-WALL### 3 strategy 0 ###LEFT-WALL### 25 move 0 ###LEFT-WALL### 34 . 1 this 3 strategy 2 important 3 strategy 3 strategy 4 has 4 has 5 allowed 5 allowed 6 researchers 5 allowed 7 to 5 allowed 18 and 7 to 18 and 8 overcome 10 barriers 8 overcome 18 and 9 the 10 barriers 10 barriers 11 that 10 barriers 12 have 11 that 12 have 12 have 13 been 13 been 14 fostered 14 fostered 15 in 15 in 17 past 16 the 17 past 18 and 19 has 19 has 20 built 20 built 22 trust 21 the 22 trust 22 trust 23 necessary 23 necessary 24 to 23 necessary 25 move 24 to 25 move 25 move 26 forward 25 move 27 into 25 move 31 to 27 into 30 approach 28 an 29 inclusive 28 an 30 approach 29 inclusive 30 approach 31 to 32 aging 32 aging 33 research not to be overlooked , an important factor to achieving success in recruitment [and] retention of diverse populations is having access to resources that allow for ongoing connection [with] research participants . 0 ###LEFT-WALL### 1 not 0 ###LEFT-WALL### 20 having 0 ###LEFT-WALL### 32 . 1 not 8 factor 1 not 19 is 2 to 3 be 2 to 5 , 2 to 8 factor 3 be 4 overlooked 6 an 7 important 6 an 8 factor 7 important 8 factor 8 factor 9 to 8 factor 19 is 9 to 10 achieving 10 achieving 11 success 10 achieving 12 in 12 in 15 retention 13 recruitment 15 retention 15 retention 16 of 16 of 18 populations 17 diverse 18 populations 19 is 20 having 20 having 21 access 20 having 22 to 22 to 23 resources 23 resources 24 that 23 resources 26 for 24 that 26 for 25 allow 26 for 26 for 31 participants 27 ongoing 28 connection 28 connection 30 research 30 research 31 participants purpose : to investigate the efficiency of a new method ( tt - upslope ) for transit time ( δt ) estimation from cardiovascular mr ( cmr ) velocity curves . 0 ###LEFT-WALL### 1 purpose 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 31 . 2 : 22 estimation 2 : 30 curves 3 to 4 investigate 3 to 21 ) 3 to 22 estimation 4 investigate 6 efficiency 4 investigate 16 for 5 the 6 efficiency 6 efficiency 7 of 7 of 10 method 8 a 10 method 9 new 10 method 10 method 12 tt 10 method 14 upslope 11 ( 12 tt 12 tt 13 - 13 - 14 upslope 14 upslope 15 ) 16 for 18 time 17 transit 18 time 18 time 20 δt 19 ( 20 δt 20 δt 21 ) 22 estimation 23 from 22 estimation 30 curves 23 from 29 velocity 24 cardiovascular 29 velocity 25 mr 27 cmr 26 ( 27 cmr 27 cmr 28 ) 27 cmr 29 velocity materials and methods : fifty healthy volunteers ( 40 ± 15 years ) underwent applanation tonometry to estimate carotid - femoral pulse wave velocity ( cf - pwv ) and carotid pressure measurements , and cmr to estimate aortic arch - pwv and ascending aorta distensibility ( aad ) . 0 ###LEFT-WALL### 3 methods 0 ###LEFT-WALL### 4 : 1 materials 2 and 2 and 3 methods 4 : 7 volunteers 4 : 14 underwent 4 : 41 - 5 fifty 7 volunteers 6 healthy 7 volunteers 7 volunteers 12 years 7 volunteers 14 underwent 8 ( 12 years 9 40 12 years 10 ± 12 years 11 15 12 years 12 years 13 ) 14 underwent 30 and 15 applanation 16 tonometry 16 tonometry 17 to 16 tonometry 30 and 17 to 19 carotid 18 estimate 19 carotid 19 carotid 24 velocity 20 - 24 velocity 21 femoral 24 velocity 22 pulse 24 velocity 23 wave 24 velocity 24 velocity 26 cf 24 velocity 28 pwv 24 velocity 29 ) 25 ( 26 cf 26 cf 27 - 27 - 28 pwv 28 pwv 29 ) 30 and 40 arch 30 and 41 - 31 carotid 32 pressure 32 pressure 40 arch 33 measurements 35 and 34 , 35 and 35 and 36 cmr 35 and 37 to 35 and 38 estimate 35 and 40 arch 37 to 38 estimate 39 aortic 40 arch 41 - 43 and 41 - 50 . 42 pwv 43 and 43 and 46 distensibility 43 and 48 aad 44 ascending 45 aorta 45 aorta 46 distensibility 47 ( 48 aad 48 aad 49 ) the δt was calculated with tt - upslope by minimizing the area delimited by two sigmoid curves fitted to the systolic upslope of the ascending ( aac ) and descending [(] dac ) aorta velocity curves , and compared with previously described methods [:] tt - point using the half maximum of aac and dac , tt - foot using aac and dac feet , and tt - wave by minimizing the area between aac and dac curves using cross correlation . 0 ###LEFT-WALL### 2 δt 0 ###LEFT-WALL### 7 - 1 the 2 δt 2 δt 3 was 3 was 4 calculated 4 calculated 5 with 5 with 6 tt 7 - 8 upslope 7 - 13 delimited 8 upslope 9 by 8 upslope 13 delimited 9 by 10 minimizing 10 minimizing 12 area 11 the 12 area 13 delimited 14 by 13 delimited 17 curves 13 delimited 19 to 14 by 15 two 16 sigmoid 17 curves 17 curves 18 fitted 19 to 29 and 20 the 22 upslope 21 systolic 22 upslope 22 upslope 23 of 22 upslope 29 and 23 of 25 ascending 24 the 25 ascending 25 ascending 27 aac 26 ( 27 aac 27 aac 28 ) 29 and 32 dac 29 and 33 ) 29 and 35 velocity 29 and 38 and 30 descending 32 dac 34 aorta 35 velocity 35 velocity 38 and 36 curves 38 and 37 , 38 and 38 and 39 compared 38 and 40 with 38 and 47 point 40 with 43 methods 41 previously 42 described 42 described 43 methods 45 tt 46 - 45 tt 47 point 47 point 48 using 48 using 50 half 49 the 50 half 50 half 54 and 50 half 59 foot 51 maximum 52 of 51 maximum 54 and 52 of 53 aac 54 and 55 dac 54 and 57 tt 54 and 59 foot 56 , 57 tt 57 tt 58 - 59 foot 60 using 60 using 66 and 61 aac 62 and 62 and 64 feet 62 and 66 and 63 dac 64 feet 65 , 66 and 66 and 67 tt 66 and 68 - 66 and 76 and 68 - 76 and 69 wave 70 by 69 wave 74 between 69 wave 76 and 70 by 71 minimizing 71 minimizing 73 area 72 the 73 area 74 between 75 aac 76 and 78 curves 76 and 79 using 76 and 82 . 77 dac 78 curves 79 using 81 correlation 80 cross 81 correlation results : all the δt methods provided a high reproducibility of arch - pwv . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 3 all 2 : 7 provided 2 : 15 . 3 all 4 the 3 all 6 methods 3 all 7 provided 4 the 6 methods 5 δt 6 methods 7 provided 10 reproducibility 8 a 9 high 8 a 10 reproducibility 9 high 10 reproducibility 10 reproducibility 11 of 11 of 14 pwv 12 arch 13 - 12 arch 14 pwv however , tt - upslope and tt - wave resulted in better correlations with aging ( r = 0.83/r = 0.83 [versus] r = [0.47/r] = 0.72 ) , cf - pwv ( r = [0.69/r] = 0.70 [versus] r = 0.34/r [=] 0.59 [ )(, and aad ( r = 0.81/r = 0.71 [versus] r = [0.61/r] = 0.60 [ )( 0 ###LEFT-WALL### 3 tt 0 ###LEFT-WALL### 10 resulted 1 however 2 , 1 however 3 tt 3 tt 8 - 3 tt 10 resulted 4 - 8 - 5 upslope 6 and 6 and 7 tt 6 and 8 - 8 - 9 wave 10 resulted 11 in 10 resulted 14 with 11 in 13 correlations 12 better 13 correlations 14 with 15 aging 15 aging 18 = 16 ( 18 = 17 r 18 = 18 = 30 cf 19 0.83/r 26 = 19 0.83/r 29 , 19 0.83/r 30 cf 20 = 21 0.83 21 0.83 24 = 23 r 24 = 24 = 26 = 26 = 27 0.72 26 = 28 ) 30 cf 37 = 31 - 37 = 32 pwv 35 = 33 ( 35 = 34 r 35 = 35 = 37 = 37 = 38 0.70 38 0.70 41 = 40 r 41 = 41 = 47 and 42 0.34/r 44 0.59 42 0.34/r 47 and 46 )(, 47 and 47 and 48 aad 48 aad 51 = 49 ( 51 = 50 r 51 = 51 = 52 0.81/r 52 0.81/r 59 = 53 = 54 0.71 54 0.71 57 = 56 r 57 = 57 = 59 = 59 = 60 0.60 59 = 62 )( furthermore , tt - upslope resulted in stronger relationship [between] arch - pwv and aad according to a theoretical model and provided better characterization of older subjects compared with tt - wave . 0 ###LEFT-WALL### 5 upslope 0 ###LEFT-WALL### 21 and 0 ###LEFT-WALL### 31 - 1 furthermore 5 upslope 2 , 3 tt 3 tt 4 - 3 tt 5 upslope 5 upslope 21 and 6 resulted 7 in 6 resulted 17 to 6 resulted 21 and 7 in 14 and 8 stronger 9 relationship 9 relationship 13 pwv 11 arch 12 - 11 arch 13 pwv 13 pwv 14 and 14 and 15 aad 16 according 17 to 17 to 20 model 18 a 19 theoretical 18 a 20 model 19 theoretical 20 model 21 and 22 provided 22 provided 24 characterization 22 provided 29 with 23 better 24 characterization 24 characterization 25 of 24 characterization 28 compared 25 of 27 subjects 26 older 27 subjects 29 with 30 tt 31 - 32 wave 31 - 33 . conclusion : arch - pwv estimated with cmr using the tt - upslope method was found to be reproducible and accurate , providing strong correlations with age and aortic stiffness indices . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 12 - 0 ###LEFT-WALL### 18 be 1 conclusion 2 : 2 : 3 arch 3 arch 5 pwv 4 - 5 pwv 5 pwv 6 estimated 5 pwv 7 with 5 pwv 12 - 7 with 8 cmr 8 cmr 9 using 9 using 11 tt 10 the 11 tt 12 - 18 be 13 upslope 14 method 14 method 15 was 15 was 16 found 16 found 17 to 17 to 18 be 18 be 20 and 19 reproducible 20 and 20 and 21 accurate 21 accurate 23 providing 22 , 23 providing 23 providing 25 correlations 23 providing 26 with 23 providing 32 . 24 strong 25 correlations 26 with 28 and 27 age 28 and 28 and 31 indices 28 and 32 . 29 aortic 31 indices 30 stiffness 31 indices background : epidural analgesia is considered fundamental in enhanced recovery protocols ( erps ) . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 4 analgesia 2 : 6 considered 2 : 15 . 3 epidural 4 analgesia 4 analgesia 5 is 5 is 6 considered 6 considered 7 fundamental 7 fundamental 8 in 8 in 11 protocols 9 enhanced 10 recovery 10 recovery 11 protocols 11 protocols 13 erps 12 ( 13 erps 13 erps 14 ) however , its value in laparoscopic colorectal surgery is unclear . 0 ###LEFT-WALL### 4 value 0 ###LEFT-WALL### 9 is 0 ###LEFT-WALL### 11 . 1 however 2 , 1 however 4 value 3 its 4 value 4 value 5 in 4 value 9 is 5 in 8 surgery 6 laparoscopic 8 surgery 7 colorectal 8 surgery 9 is 10 unclear the aim of this study was to examine the effects of different analgesic regimens on outcomes following laparoscopic colorectal surgery in fluid - optimized patients treated within an erp . 0 ###LEFT-WALL### 2 aim 0 ###LEFT-WALL### 30 . 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 examine 7 to 8 examine 8 examine 10 effects 8 examine 27 within 9 the 10 effects 10 effects 11 of 10 effects 17 following 11 of 14 regimens 12 different 13 analgesic 13 analgesic 14 regimens 14 regimens 15 on 15 on 16 outcomes 17 following 20 surgery 17 following 21 in 18 laparoscopic 20 surgery 19 colorectal 20 surgery 21 in 25 patients 22 fluid 23 - 22 fluid 25 patients 24 optimized 25 patients 25 patients 26 treated 27 within 29 erp 28 an 29 erp methods : ninety - nine patients were randomized to receive epidural , spinal or patient - controlled ( pca ) analgesia . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 22 . 2 : 6 patients 2 : 10 receive 3 ninety 4 - 4 - 5 nine 4 - 6 patients 6 patients 7 were 7 were 8 randomized 8 randomized 9 to 9 to 10 receive 10 receive 21 analgesia 11 epidural 14 or 11 epidural 21 analgesia 12 , 14 or 13 spinal 14 or 14 or 15 patient 14 or 16 - 14 or 17 controlled 14 or 19 pca 14 or 20 ) 18 ( 19 pca 19 pca 20 ) the primary endpoints were time until medically fit for discharge and length [of] hospital stay . 0 ###LEFT-WALL### 3 endpoints 0 ###LEFT-WALL### 4 were 0 ###LEFT-WALL### 16 . 1 the 3 endpoints 2 primary 3 endpoints 3 endpoints 4 were 4 were 5 time 4 were 6 until 6 until 11 and 6 until 15 stay 7 medically 11 and 8 fit 9 for 8 fit 11 and 9 for 10 discharge 11 and 14 hospital 11 and 15 stay 12 length 14 hospital secondary endpoints included return of bowel function [,] pain scores , and changes in pulmonary function [and] quality of life . 0 ###LEFT-WALL### 2 endpoints 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 21 . 1 secondary 2 endpoints 2 endpoints 12 and 3 included 4 return 3 included 12 and 4 return 5 of 5 of 10 scores 6 bowel 10 scores 7 function 9 pain 9 pain 10 scores 11 , 12 and 12 and 13 changes 12 and 14 in 14 in 18 quality 15 pulmonary 16 function 16 function 18 quality 18 quality 19 of 19 of 20 life results : ninety - one patients completed the study . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 3 ninety 2 : 4 - 2 : 10 . 4 - 5 one 5 one 6 patients 5 one 7 completed 6 patients 7 completed 7 completed 9 study 8 the 9 study the median length [of] hospital stay was 3.7 days following epidural analgesia [,] significantly longer than that of 2.7 and 2.8 days for spinal analgesia and pca respectively ( p = 0.002 [and] p < 0.001 ) . 0 ###LEFT-WALL### 6 stay 0 ###LEFT-WALL### 7 was 0 ###LEFT-WALL### 38 . 1 the 6 stay 2 median 3 length 3 length 6 stay 5 hospital 6 stay 6 stay 7 was 7 was 12 analgesia 8 3.7 9 days 9 days 10 following 10 following 12 analgesia 11 epidural 12 analgesia 12 analgesia 15 longer 14 significantly 15 longer 15 longer 16 than 15 longer 28 respectively 15 longer 31 = 15 longer 35 < 16 than 26 and 17 that 18 of 17 that 26 and 18 of 22 days 19 2.7 20 and 20 and 21 2.8 20 and 22 days 22 days 23 for 23 for 25 analgesia 24 spinal 25 analgesia 26 and 27 pca 29 ( 31 = 30 p 31 = 31 = 32 0.002 34 p 35 < 35 < 36 0.001 35 < 37 ) there was also a slower return [of] bowel function with epidural analgesia than with spinal analgesia and pca . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 was 0 ###LEFT-WALL### 19 . 1 there 2 was 2 was 3 also 2 was 9 function 2 was 13 than 4 a 9 function 5 slower 6 return 6 return 9 function 8 bowel 9 function 9 function 10 with 10 with 12 analgesia 11 epidural 12 analgesia 13 than 14 with 14 with 17 and 15 spinal 16 analgesia 16 analgesia 17 and 17 and 18 pca epidural analgesia did not offer better preservation of pulmonary function [or] quality of life , although pain scores were higher in the pca group in the early postoperative period . 0 ###LEFT-WALL### 2 analgesia 0 ###LEFT-WALL### 19 were 0 ###LEFT-WALL### 30 . 1 epidural 2 analgesia 2 analgesia 3 did 3 did 4 not 3 did 5 offer 5 offer 7 preservation 5 offer 16 although 6 better 7 preservation 7 preservation 8 of 8 of 12 quality 9 pulmonary 10 function 10 function 12 quality 12 quality 13 of 13 of 14 life 15 , 16 although 16 although 18 scores 17 pain 18 scores 18 scores 19 were 19 were 20 higher 20 higher 21 in 20 higher 25 in 21 in 24 group 22 the 24 group 23 pca 24 group 25 in 29 period 26 the 29 period 27 early 29 period 28 postoperative 29 period conclusion : many of the outcomes in the epidural analgesia group were significantly worse than those in the spinal analgesia and pca groups , suggesting that either of these two modalities could replace epidural analgesia . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 3 many 2 : 12 were 3 many 4 of 3 many 12 were 4 of 6 outcomes 5 the 6 outcomes 6 outcomes 7 in 7 in 11 group 8 the 11 group 9 epidural 10 analgesia 10 analgesia 11 group 12 were 13 significantly 12 were 14 worse 14 worse 15 than 14 worse 17 in 15 than 16 those 17 in 21 and 18 the 20 analgesia 19 spinal 20 analgesia 20 analgesia 21 and 21 and 23 groups 21 and 25 suggesting 22 pca 23 groups 24 , 25 suggesting 25 suggesting 26 that 25 suggesting 36 . 26 that 27 either 26 that 33 replace 27 either 28 of 27 either 32 could 28 of 31 modalities 29 these 30 two 30 two 31 modalities 32 could 33 replace 33 replace 35 analgesia 34 epidural 35 analgesia histomorphometric aging methods report varying degrees of precision , measured through standard error of the estimate ( see ) . 0 ###LEFT-WALL### 3 methods 0 ###LEFT-WALL### 4 report 0 ###LEFT-WALL### 20 . 1 histomorphometric 2 aging 2 aging 3 methods 3 methods 4 report 4 report 8 precision 4 report 10 measured 5 varying 6 degrees 6 degrees 7 of 6 degrees 8 precision 7 of 8 precision 9 , 10 measured 10 measured 11 through 10 measured 19 ) 11 through 13 error 12 standard 13 error 13 error 14 of 14 of 18 see 15 the 18 see 16 estimate 18 see 17 ( 18 see these techniques have been developed from variable samples sizes ( [n] [ )(and the impact of [n] on reported aging precision has not been rigorously examined in the anthropological literature . 0 ###LEFT-WALL### 2 techniques 0 ###LEFT-WALL### 5 developed 0 ###LEFT-WALL### 13 )(and 0 ###LEFT-WALL### 31 . 1 these 2 techniques 2 techniques 3 have 3 have 4 been 4 been 5 developed 5 developed 6 from 6 from 9 sizes 7 variable 8 samples 8 samples 9 sizes 10 ( 13 )(and 13 )(and 15 impact 13 )(and 26 examined 14 the 15 impact 15 impact 16 of 15 impact 22 has 16 of 18 on 18 on 21 precision 19 reported 21 precision 20 aging 21 precision 22 has 23 not 22 has 24 been 24 been 25 rigorously 24 been 26 examined 26 examined 27 in 27 in 30 literature 28 the 30 literature 29 anthropological 30 literature this brief communication explores the relation between [n] [and] see through a review of the literature ( abstracts , articles , book chapters , theses , and dissertations ) , predictions based upon sampling theory and a simulation . 0 ###LEFT-WALL### 3 communication 0 ###LEFT-WALL### 4 explores 1 this 3 communication 2 brief 3 communication 3 communication 4 explores 4 explores 6 relation 4 explores 7 between 4 explores 11 through 5 the 6 relation 7 between 10 see 11 through 27 and 12 a 13 review 13 review 14 of 13 review 27 and 14 of 16 literature 15 the 16 literature 16 literature 18 abstracts 16 literature 20 articles 16 literature 25 theses 17 ( 18 abstracts 18 abstracts 19 , 19 , 20 articles 20 articles 23 chapters 20 articles 24 , 21 , 23 chapters 22 book 23 chapters 23 chapters 24 , 24 , 25 theses 25 theses 26 , 26 , 27 and 27 and 28 dissertations 27 and 29 ) 27 and 36 and 30 , 36 and 31 predictions 32 based 31 predictions 33 upon 31 predictions 36 and 33 upon 34 sampling 34 sampling 35 theory 36 and 38 simulation 36 and 39 . 37 a 38 simulation published see values for age prediction , derived from 40 studies , range from 1.51 to 16.48 years ( mean 8.63 [;] s [d] [:] 3.81 years ) . 0 ###LEFT-WALL### 7 , 0 ###LEFT-WALL### 29 . 1 published 3 values 1 published 7 , 2 see 3 values 3 values 4 for 4 for 6 prediction 5 age 6 prediction 7 , 8 derived 8 derived 9 from 9 from 11 studies 10 40 11 studies 11 studies 13 range 12 , 13 range 13 range 14 from 13 range 28 ) 14 from 18 years 15 1.51 16 to 16 to 17 16.48 16 to 18 years 18 years 27 years 19 ( 27 years 20 mean 27 years 21 8.63 23 s 23 s 27 years 26 3.81 27 years 27 years 28 ) in general , these values are widely distributed for smaller samples and the distribution narrows as [n] increases -- a pattern expected from sampling theory . 0 ###LEFT-WALL### 5 values 0 ###LEFT-WALL### 8 distributed 0 ###LEFT-WALL### 12 and 1 in 2 general 2 general 3 , 2 general 5 values 4 these 5 values 5 values 6 are 6 are 8 distributed 7 widely 8 distributed 8 distributed 9 for 9 for 11 samples 10 smaller 11 samples 12 and 14 distribution 12 and 15 narrows 13 the 14 distribution 14 distribution 15 narrows 15 narrows 16 as 16 as 18 increases 18 increases 21 pattern 19 -- 21 pattern 20 a 21 pattern 21 pattern 22 expected 21 pattern 26 . 22 expected 23 from 23 from 24 sampling 24 sampling 25 theory for the two studies that have samples in excess of 200 individuals , the see values are [very] similar ( [10.08] and 11.10 years ) with a mean of 10.59 years . 0 ###LEFT-WALL### 16 values 0 ###LEFT-WALL### 17 are 0 ###LEFT-WALL### 32 . 1 for 4 studies 1 for 16 values 2 the 3 two 3 two 4 studies 4 studies 5 that 4 studies 6 have 5 that 6 have 6 have 7 samples 8 in 9 excess 8 in 13 , 8 in 16 values 9 excess 10 of 10 of 12 individuals 11 200 12 individuals 14 the 16 values 15 see 16 values 16 values 17 are 17 are 22 and 17 are 26 with 19 similar 22 and 20 ( 22 and 22 and 24 years 22 and 25 ) 23 11.10 24 years 26 with 28 mean 27 a 28 mean 28 mean 29 of 29 of 31 years 30 10.59 31 years assuming this mean value is [a] ['] true ['] characterization of the error at the population level , [the] 95 % confidence intervals for see values from samples of 10 , 50 , and 150 individuals are on the order of ± 4.2 , 1.7 , [and] 1.0 years , [respectively] . 0 ###LEFT-WALL### 1 assuming 0 ###LEFT-WALL### 5 is 1 assuming 4 value 1 assuming 5 is 2 this 4 value 3 mean 4 value 5 is 10 characterization 8 true 10 characterization 10 characterization 11 of 11 of 13 error 12 the 13 error 13 error 14 at 13 error 24 for 14 at 23 intervals 15 the 23 intervals 16 population 23 intervals 17 level 18 , 17 level 22 confidence 20 95 21 % 21 % 22 confidence 22 confidence 23 intervals 24 for 25 see 25 see 34 and 25 see 37 are 26 values 27 from 26 values 29 of 26 values 34 and 27 from 28 samples 29 of 30 10 30 10 32 50 31 , 32 50 32 50 33 , 34 and 36 individuals 34 and 37 are 35 150 36 individuals 37 are 38 on 38 on 40 order 39 the 40 order 40 order 41 of 40 order 45 1.7 41 of 42 ± 42 ± 43 4.2 44 , 45 1.7 45 1.7 49 years 45 1.7 52 . 46 , 49 years 48 1.0 49 years 49 years 50 , while numerous sources of variation potentially affect the precision of different methods , the impact of sample size cannot be overlooked . 0 ###LEFT-WALL### 15 impact 0 ###LEFT-WALL### 21 overlooked 0 ###LEFT-WALL### 22 . 1 while 3 sources 1 while 7 affect 1 while 13 , 1 while 15 impact 2 numerous 3 sources 3 sources 4 of 3 sources 7 affect 4 of 5 variation 6 potentially 7 affect 7 affect 9 precision 8 the 9 precision 9 precision 10 of 10 of 12 methods 11 different 12 methods 14 the 15 impact 15 impact 16 of 15 impact 19 cannot 16 of 18 size 17 sample 18 size 19 cannot 20 be 20 be 21 overlooked the uncertainty associated with see values derived from smaller samples complicates the comparison of approaches based upon different methodology [and/or] skeletal elements . 0 ###LEFT-WALL### 2 uncertainty 0 ###LEFT-WALL### 11 complicates 0 ###LEFT-WALL### 23 . 1 the 2 uncertainty 2 uncertainty 3 associated 2 uncertainty 11 complicates 3 associated 4 with 4 with 6 values 5 see 6 values 6 values 7 derived 7 derived 8 from 8 from 10 samples 9 smaller 10 samples 11 complicates 13 comparison 12 the 13 comparison 13 comparison 14 of 13 comparison 16 based 14 of 15 approaches 16 based 17 upon 17 upon 22 elements 18 different 19 methodology 19 methodology 22 elements 21 skeletal 22 elements meaningful comparisons require larger samples than have frequently been used and should ideally be based upon standardized samples . 0 ###LEFT-WALL### 2 comparisons 0 ###LEFT-WALL### 3 require 0 ###LEFT-WALL### 19 . 1 meaningful 2 comparisons 2 comparisons 3 require 3 require 5 samples 4 larger 5 samples 5 samples 11 and 6 than 7 have 7 have 9 been 7 have 11 and 8 frequently 9 been 9 been 10 used 11 and 12 should 11 and 16 upon 12 should 14 be 13 ideally 14 be 14 be 15 based 16 upon 18 samples 17 standardized 18 samples calcification is a pathological process that may lead to impairment of nutrient supply and disc metabolism in degenerative and scoliotic intervertebral discs ( ivds ) . 0 ###LEFT-WALL### 1 calcification 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 26 . 1 calcification 2 is 2 is 5 process 2 is 9 to 2 is 17 in 3 a 5 process 4 pathological 5 process 5 process 6 that 5 process 7 may 6 that 7 may 7 may 8 lead 9 to 14 and 10 impairment 11 of 10 impairment 14 and 11 of 13 supply 12 nutrient 13 supply 14 and 16 metabolism 15 disc 16 metabolism 17 in 22 discs 18 degenerative 19 and 19 and 20 scoliotic 19 and 22 discs 21 intervertebral 22 discs 22 discs 24 ivds 23 ( 24 ivds 24 ivds 25 ) the purpose of this study was to assess the calcification potential of ivds in degenerative disc disease ( ddd ) and adolescent idiopathic scoliosis ( ais ) . 0 ###LEFT-WALL### 2 purpose 0 ###LEFT-WALL### 28 . 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 assess 7 to 8 assess 8 assess 11 potential 9 the 11 potential 10 calcification 11 potential 11 potential 12 of 12 of 21 and 13 ivds 14 in 13 ivds 21 and 14 in 17 disease 15 degenerative 16 disc 16 disc 17 disease 17 disease 19 ddd 18 ( 19 ddd 19 ddd 20 ) 21 and 24 scoliosis 21 and 26 ais 22 adolescent 24 scoliosis 23 idiopathic 24 scoliosis 25 ( 26 ais 26 ais 27 ) for this purpose , 34 ivds from 16 adult patients with ddd and 25 ivds from 9 adolescent patients with ais were obtained at surgery . 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 23 obtained 0 ###LEFT-WALL### 26 . 1 for 3 purpose 1 for 4 , 1 for 13 and 2 this 3 purpose 5 34 6 ivds 6 ivds 7 from 6 ivds 11 with 6 ivds 13 and 7 from 10 patients 8 16 10 patients 9 adult 10 patients 11 with 12 ddd 13 and 15 ivds 13 and 16 from 13 and 20 with 13 and 22 were 14 25 15 ivds 16 from 19 patients 17 9 19 patients 18 adolescent 19 patients 20 with 21 ais 22 were 23 obtained 23 obtained 24 at 24 at 25 surgery the concave and convex parts of the scoliotic discs were analyzed separately . 0 ###LEFT-WALL### 5 parts 0 ###LEFT-WALL### 11 analyzed 0 ###LEFT-WALL### 13 . 1 the 5 parts 2 concave 3 and 3 and 4 convex 3 and 5 parts 5 parts 6 of 5 parts 10 were 6 of 9 discs 7 the 9 discs 8 scoliotic 9 discs 10 were 11 analyzed 11 analyzed 12 separately von kossa staining was performed to visualize calcium deposits , while type x collagen ( col x ) expression associated with endochondral ossification was measured by immunohistochemistry . 0 ###LEFT-WALL### 2 kossa 0 ###LEFT-WALL### 7 visualize 0 ###LEFT-WALL### 10 , 0 ###LEFT-WALL### 28 . 1 von 2 kossa 2 kossa 3 staining 2 kossa 4 was 4 was 5 performed 5 performed 6 to 6 to 7 visualize 7 visualize 9 deposits 8 calcium 9 deposits 10 , 19 expression 10 , 25 measured 11 while 12 type 11 while 19 expression 12 type 13 x 14 collagen 16 col 14 collagen 18 ) 14 collagen 19 expression 15 ( 16 col 16 col 17 x 16 col 18 ) 19 expression 20 associated 19 expression 24 was 20 associated 21 with 21 with 23 ossification 22 endochondral 23 ossification 24 was 25 measured 25 measured 26 by 26 by 27 immunohistochemistry alkaline phosphatase activity and calcium and inorganic phosphate concentrations were used as indicators of calcification potential . 0 ###LEFT-WALL### 6 and 0 ###LEFT-WALL### 11 used 0 ###LEFT-WALL### 17 . 1 alkaline 2 phosphatase 2 phosphatase 3 activity 3 activity 4 and 4 and 5 calcium 4 and 6 and 6 and 9 concentrations 6 and 10 were 7 inorganic 9 concentrations 8 phosphate 9 concentrations 10 were 11 used 11 used 12 as 12 as 13 indicators 13 indicators 14 of 14 of 16 potential 15 calcification 16 potential results showed the presence of calcium deposits and col x in degenerative and scoliotic ivds , but not in control discs , and the level of the indicators of calcification potential was consistently higher in degenerative and scoliotic discs than in control discs . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 showed 0 ###LEFT-WALL### 23 and 0 ###LEFT-WALL### 44 . 1 results 2 showed 2 showed 4 presence 2 showed 7 deposits 2 showed 8 and 3 the 4 presence 4 presence 5 of 5 of 6 calcium 8 and 9 col 9 col 10 x 9 col 17 but 11 in 13 and 11 in 17 but 12 degenerative 13 and 13 and 15 ivds 14 scoliotic 15 ivds 16 , 17 but 17 but 18 not 17 but 19 in 19 in 21 discs 20 control 21 discs 22 , 23 and 23 and 25 level 23 and 32 was 24 the 25 level 25 level 26 of 25 level 29 of 25 level 32 was 26 of 28 indicators 27 the 28 indicators 29 of 31 potential 30 calcification 31 potential 32 was 34 higher 32 was 35 in 32 was 40 than 33 consistently 34 higher 35 in 39 discs 36 degenerative 37 and 37 and 38 scoliotic 37 and 39 discs 40 than 41 in 41 in 43 discs 42 control 43 discs the results suggest that disc degeneration in adults is associated with ongoing mineral deposition and that mineralization in ais discs might reflect a premature degenerative process . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 suggest 0 ###LEFT-WALL### 27 . 1 the 2 results 2 results 3 suggest 3 suggest 15 and 4 that 6 degeneration 4 that 10 associated 4 that 15 and 5 disc 6 degeneration 6 degeneration 7 in 6 degeneration 9 is 7 in 8 adults 9 is 10 associated 10 associated 11 with 11 with 14 deposition 12 ongoing 14 deposition 13 mineral 14 deposition 15 and 16 that 16 that 17 mineralization 16 that 22 reflect 17 mineralization 18 in 17 mineralization 21 might 18 in 20 discs 19 ais 20 discs 21 might 22 reflect 22 reflect 26 process 23 a 24 premature 23 a 26 process 24 premature 26 process 25 degenerative 26 process data from this multiyear qualitative study of the effects of hurricane katrina and flooding in new orleans suggest differences in [how] the elderly cope with disaster . 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 18 suggest 0 ###LEFT-WALL### 27 . 1 data 2 from 1 data 13 and 2 from 6 study 3 this 4 multiyear 4 multiyear 6 study 5 qualitative 6 study 6 study 7 of 7 of 9 effects 8 the 9 effects 9 effects 10 of 10 of 12 katrina 11 hurricane 12 katrina 13 and 14 flooding 13 and 15 in 13 and 18 suggest 15 in 17 orleans 16 new 17 orleans 18 suggest 19 differences 18 suggest 20 in 18 suggest 25 with 20 in 24 cope 22 the 24 cope 23 elderly 24 cope 25 with 26 disaster at the time of the disaster , the elderly of new orleans were at greater risk than other groups , and [more] elderly died than any other group during the storm and in the first year [after] . 0 ###LEFT-WALL### 21 and 0 ###LEFT-WALL### 24 died 0 ###LEFT-WALL### 38 . 1 at 3 time 1 at 7 , 1 at 21 and 2 the 3 time 3 time 4 of 4 of 6 disaster 5 the 6 disaster 8 the 9 elderly 9 elderly 10 of 9 elderly 21 and 10 of 11 new 11 new 12 orleans 11 new 13 were 12 orleans 13 were 13 were 14 at 13 were 17 than 14 at 16 risk 15 greater 16 risk 17 than 19 groups 18 other 19 groups 20 , 21 and 21 and 23 elderly 21 and 24 died 24 died 25 than 25 than 28 group 26 any 27 other 27 other 28 group 28 group 32 and 29 during 31 storm 29 during 32 and 30 the 31 storm 32 and 33 in 33 in 36 year 34 the 36 year 35 first 36 year those who did survive beyond the first year report coping with the long - term disaster aftermath better than the generation below them , experiencing heightened stresses , and feeling as if they are " aging " faster than they should . 0 ###LEFT-WALL### 1 those 0 ###LEFT-WALL### 9 report 0 ###LEFT-WALL### 42 . 1 those 2 who 1 those 3 did 1 those 9 report 2 who 3 did 3 did 4 survive 4 survive 5 beyond 5 beyond 8 year 6 the 7 first 6 the 8 year 9 report 10 coping 9 report 26 heightened 10 coping 11 with 10 coping 26 heightened 11 with 25 experiencing 12 the 25 experiencing 13 long 17 aftermath 13 long 24 , 13 long 25 experiencing 14 - 17 aftermath 15 term 16 disaster 16 disaster 17 aftermath 17 aftermath 18 better 17 aftermath 24 , 18 better 19 than 18 better 22 below 19 than 21 generation 20 the 21 generation 22 below 23 them 26 heightened 29 and 26 heightened 32 if 26 heightened 38 faster 26 heightened 39 than 27 stresses 29 and 28 , 29 and 29 and 30 feeling 31 as 32 if 32 if 33 they 32 if 36 aging 33 they 34 are 34 are 35 " 34 are 36 aging 36 aging 37 " 39 than 40 they 39 than 41 should 40 they 41 should we offer insight on how we might define and characterize disasters , and illustrate that long - term catastrophes " age " in specific ways . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 17 - 1 we 9 and 2 offer 3 insight 2 offer 9 and 3 insight 4 on 3 insight 6 we 3 insight 8 define 4 on 5 how 6 we 7 might 7 might 8 define 9 and 13 and 9 and 16 long 10 characterize 11 disasters 10 characterize 13 and 12 , 13 and 13 and 14 illustrate 15 that 16 long 17 - 18 term 17 - 26 . 18 term 19 catastrophes 18 term 21 age 18 term 23 in 19 catastrophes 20 " 21 age 22 " 23 in 25 ways 24 specific 25 ways the objective of the minnesota live well at home program ( lwah ) was to develop a screening tool that targets private - pay older persons at risk for nursing home admission or assisted living entry and delivers a multi - component " diversion " service program to support these clients . 0 ###LEFT-WALL### 2 objective 0 ###LEFT-WALL### 21 targets 0 ###LEFT-WALL### 52 . 1 the 2 objective 2 objective 3 of 2 objective 8 at 2 objective 12 lwah 2 objective 14 was 3 of 7 well 4 the 7 well 5 minnesota 6 live 6 live 7 well 8 at 10 program 9 home 10 program 11 ( 12 lwah 12 lwah 13 ) 14 was 15 to 14 was 16 develop 15 to 16 develop 16 develop 19 tool 17 a 19 tool 18 screening 19 tool 19 tool 20 that 19 tool 21 targets 20 that 21 targets 21 targets 24 pay 21 targets 48 to 22 private 23 - 22 private 24 pay 24 pay 26 persons 24 pay 38 delivers 25 older 26 persons 26 persons 27 at 26 persons 33 or 27 at 28 risk 28 risk 29 for 29 for 30 nursing 31 home 32 admission 31 home 33 or 33 or 37 and 34 assisted 36 entry 34 assisted 37 and 35 living 36 entry 37 and 38 delivers 38 delivers 47 program 39 a 40 multi 39 a 47 program 40 multi 41 - 40 multi 47 program 42 component 43 " 42 component 44 diversion 44 diversion 45 " 44 diversion 46 service 46 service 47 program 48 to 49 support 49 support 51 clients 50 these 51 clients two hundred sixty - one clients completed the brief screening protocol , [and] 3 - month telephone surveys ( n=119 ) collected additional pilot evaluation data to determine content of diversion service support and satisfaction with various lwah components . 0 ###LEFT-WALL### 3 sixty 0 ###LEFT-WALL### 22 collected 0 ###LEFT-WALL### 40 . 1 two 2 hundred 2 hundred 3 sixty 3 sixty 5 one 3 sixty 18 surveys 3 sixty 22 collected 4 - 5 one 5 one 6 clients 5 one 10 screening 5 one 15 - 6 clients 7 completed 7 completed 9 brief 8 the 9 brief 9 brief 10 screening 10 screening 11 protocol 11 protocol 14 3 12 , 14 3 14 3 15 - 15 - 18 surveys 16 month 18 surveys 17 telephone 18 surveys 18 surveys 20 n=119 18 surveys 21 ) 19 ( 20 n=119 20 n=119 21 ) 22 collected 26 data 22 collected 27 to 22 collected 36 with 23 additional 24 pilot 24 pilot 25 evaluation 25 evaluation 26 data 27 to 28 determine 28 determine 29 content 29 content 30 of 30 of 34 and 31 diversion 32 service 32 service 33 support 33 support 34 and 34 and 35 satisfaction 36 with 39 components 37 various 39 components 38 lwah 39 components the preliminary findings showed that the screening tool was delivered efficiently and targeted clients at potential high risk for residential care placement . 0 ###LEFT-WALL### 3 findings 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 23 . 1 the 3 findings 2 preliminary 3 findings 3 findings 12 and 4 showed 5 that 4 showed 12 and 5 that 8 tool 5 that 10 delivered 6 the 8 tool 7 screening 8 tool 8 tool 9 was 9 was 10 delivered 10 delivered 11 efficiently 12 and 13 targeted 12 and 15 at 13 targeted 14 clients 15 at 18 risk 16 potential 18 risk 17 high 18 risk 18 risk 19 for 19 for 22 placement 20 residential 21 care 21 care 22 placement clients were also satisfied with the multi - component lwah service . 0 ###LEFT-WALL### 1 clients 0 ###LEFT-WALL### 2 were 0 ###LEFT-WALL### 12 . 1 clients 2 were 2 were 3 also 2 were 4 satisfied 4 satisfied 5 with 5 with 11 service 6 the 11 service 7 multi 8 - 7 multi 9 component 9 component 11 service 10 lwah 11 service the results provide support for the feasibility of a lwah risk management process that links community [-] residing older persons with community [-] based long - term care options . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 provide 0 ###LEFT-WALL### 30 . 1 the 2 results 2 results 3 provide 3 provide 4 support 3 provide 21 with 4 support 5 for 4 support 8 of 4 support 14 that 4 support 15 links 5 for 7 feasibility 6 the 7 feasibility 8 of 13 process 9 a 13 process 10 lwah 13 process 11 risk 12 management 12 management 13 process 14 that 15 links 15 links 20 persons 16 community 18 residing 18 residing 20 persons 19 older 20 persons 21 with 29 options 22 community 24 based 24 based 27 term 25 long 26 - 25 long 27 term 27 term 28 care 28 care 29 options the ongoing debate on u.s . healthcare reform fueled by increasing cost and poor access to quality [healthcare] is spurring interest in medical travel . 0 ###LEFT-WALL### 2 ongoing 0 ###LEFT-WALL### 3 debate 0 ###LEFT-WALL### 6 . 1 the 2 ongoing 2 ongoing 3 debate 3 debate 4 on 4 on 5 u.s 6 . 8 reform 6 . 13 and 6 . 25 . 7 healthcare 8 reform 8 reform 9 fueled 9 fueled 10 by 10 by 12 cost 11 increasing 12 cost 13 and 15 access 13 and 19 is 14 poor 15 access 15 access 16 to 15 access 19 is 16 to 17 quality 19 is 21 interest 20 spurring 21 interest 21 interest 22 in 22 in 24 travel 23 medical 24 travel the topic of medical travel - going abroad to seek medical care - has been widely reported in various news outlets . 0 ###LEFT-WALL### 2 topic 0 ###LEFT-WALL### 17 reported 0 ###LEFT-WALL### 22 . 1 the 2 topic 2 topic 3 of 2 topic 14 has 3 of 5 travel 4 medical 5 travel 5 travel 7 going 6 - 7 going 7 going 8 abroad 7 going 9 to 7 going 13 - 9 to 10 seek 10 seek 12 care 11 medical 12 care 14 has 15 been 15 been 17 reported 16 widely 17 reported 17 reported 18 in 18 in 21 outlets 19 various 21 outlets 20 news 21 outlets this issue even resulted in a senate hearing before the special committee on aging . 0 ###LEFT-WALL### 2 issue 0 ###LEFT-WALL### 4 resulted 0 ###LEFT-WALL### 15 . 1 this 2 issue 2 issue 4 resulted 3 even 4 resulted 4 resulted 5 in 4 resulted 9 before 4 resulted 13 on 5 in 8 hearing 6 a 8 hearing 7 senate 8 hearing 9 before 12 committee 10 the 12 committee 11 special 12 committee 13 on 14 aging despite this popularity , very little empirical research has been conducted [to] [describe] and understand medical travelers . 0 ###LEFT-WALL### 8 research 0 ###LEFT-WALL### 14 and 0 ###LEFT-WALL### 18 . 1 despite 3 popularity 1 despite 4 , 1 despite 8 research 2 this 3 popularity 5 very 6 little 6 little 8 research 7 empirical 8 research 8 research 9 has 9 has 10 been 10 been 14 and 11 conducted 14 and 14 and 15 understand 15 understand 17 travelers 16 medical 17 travelers to fill this gap , the present study involves in [-] depth interviews of medical travel facilitators with extensive exposure [to] and communication with medical travelers . 0 ###LEFT-WALL### 8 study 0 ###LEFT-WALL### 9 involves 0 ###LEFT-WALL### 27 . 1 to 2 fill 1 to 5 , 1 to 8 study 2 fill 4 gap 3 this 4 gap 6 the 8 study 7 present 8 study 8 study 9 involves 9 involves 10 in 9 involves 17 facilitators 9 involves 18 with 9 involves 24 with 10 in 13 interviews 12 depth 13 interviews 13 interviews 14 of 14 of 16 travel 15 medical 16 travel 18 with 22 and 19 extensive 20 exposure 20 exposure 22 and 22 and 23 communication 24 with 26 travelers 25 medical 26 travelers this article has multiple objectives . 0 ###LEFT-WALL### 2 article 0 ###LEFT-WALL### 3 has 0 ###LEFT-WALL### 6 . 1 this 2 article 2 article 3 has 3 has 5 objectives 4 multiple 5 objectives it aims to develop a demographic and psychographic profile of medical travelers and identify their underlying motives to seek medical care overseas . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 2 aims 0 ###LEFT-WALL### 23 . 1 it 2 aims 2 aims 3 to 2 aims 13 and 3 to 13 and 4 develop 9 profile 4 develop 13 and 5 a 9 profile 6 demographic 7 and 7 and 8 psychographic 7 and 9 profile 9 profile 10 of 10 of 12 travelers 11 medical 12 travelers 13 and 14 identify 14 identify 17 motives 14 identify 18 to 15 their 17 motives 16 underlying 17 motives 18 to 19 seek 19 seek 21 care 19 seek 22 overseas 20 medical 21 care based on these insights , it presents a list of propositions to be tested in further research . 0 ###LEFT-WALL### 6 it 0 ###LEFT-WALL### 7 presents 0 ###LEFT-WALL### 18 . 1 based 2 on 1 based 5 , 1 based 6 it 2 on 4 insights 3 these 4 insights 6 it 7 presents 7 presents 9 list 7 presents 12 to 7 presents 15 in 8 a 9 list 9 list 10 of 10 of 11 propositions 12 to 13 be 13 be 14 tested 15 in 17 research 16 further 17 research finally , it offers practical implications for the healthcare industry . 0 ###LEFT-WALL### 3 it 0 ###LEFT-WALL### 4 offers 0 ###LEFT-WALL### 11 . 1 finally 2 , 1 finally 3 it 3 it 4 offers 4 offers 6 implications 5 practical 6 implications 6 implications 7 for 7 for 10 industry 8 the 10 industry 9 healthcare 10 industry forefoot pes cavus is a cardinal sign of charcot - marie - tooth disease ( cmt ) . 0 ###LEFT-WALL### 3 cavus 0 ###LEFT-WALL### 4 is 0 ###LEFT-WALL### 18 . 1 forefoot 3 cavus 2 pes 3 cavus 3 cavus 4 is 4 is 7 sign 5 a 7 sign 6 cardinal 7 sign 7 sign 8 of 7 sign 14 disease 8 of 9 charcot 9 charcot 11 marie 10 - 11 marie 11 marie 12 - 12 - 14 disease 13 tooth 14 disease 14 disease 16 cmt 14 disease 17 ) 15 ( 16 cmt 16 cmt 17 ) this review is focused on the pathophysiology of pes cavus in cmt1a duplication , which is the most [common] [subtype] of the disease . 0 ###LEFT-WALL### 2 review 0 ###LEFT-WALL### 4 focused 0 ###LEFT-WALL### 14 , 0 ###LEFT-WALL### 24 . 1 this 2 review 2 review 3 is 3 is 4 focused 4 focused 5 on 4 focused 11 in 5 on 7 pathophysiology 6 the 7 pathophysiology 7 pathophysiology 8 of 8 of 10 cavus 9 pes 10 cavus 11 in 13 duplication 12 cmt1a 13 duplication 14 , 15 which 14 , 16 is 15 which 16 is 16 is 23 disease 17 the 18 most 18 most 21 of 18 most 23 disease 21 of 23 disease 22 the 23 disease assessment of foot deformities in cmt1a , their prevalence and proposed mechanisms , and recent contributions of magnetic resonance imaging studies of lower - leg [and] foot musculature are revised . 0 ###LEFT-WALL### 14 and 0 ###LEFT-WALL### 30 revised 0 ###LEFT-WALL### 31 . 1 assessment 2 of 1 assessment 14 and 2 of 4 deformities 3 foot 4 deformities 4 deformities 5 in 4 deformities 10 and 5 in 6 cmt1a 7 , 10 and 8 their 9 prevalence 9 prevalence 10 and 10 and 12 mechanisms 10 and 13 , 11 proposed 12 mechanisms 14 and 16 contributions 14 and 20 imaging 14 and 29 are 15 recent 16 contributions 16 contributions 17 of 17 of 19 resonance 18 magnetic 19 resonance 20 imaging 21 studies 21 studies 22 of 22 of 28 musculature 23 lower 24 - 23 lower 25 leg 25 leg 28 musculature 27 foot 28 musculature 29 are 30 revised special attention is given to papers on foot deformities at initial stages of the disease . 0 ###LEFT-WALL### 2 attention 0 ###LEFT-WALL### 4 given 0 ###LEFT-WALL### 16 . 1 special 2 attention 2 attention 3 is 3 is 4 given 4 given 5 to 4 given 7 on 4 given 10 at 5 to 6 papers 7 on 9 deformities 8 foot 9 deformities 10 at 12 stages 11 initial 12 stages 12 stages 13 of 13 of 15 disease 14 the 15 disease we conclude that pes cavus is an early and age - dependent manifestation of cmt1a duplication . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 conclude 0 ###LEFT-WALL### 17 . 1 we 2 conclude 2 conclude 3 that 3 that 5 cavus 3 that 6 is 4 pes 5 cavus 5 cavus 6 is 6 is 13 manifestation 7 an 13 manifestation 8 early 9 and 9 and 10 age 9 and 11 - 9 and 13 manifestation 12 dependent 13 manifestation 13 manifestation 14 of 14 of 16 duplication 15 cmt1a 16 duplication selective denervation of intrinsic foot musculature , particularly of the lumbricals , and not imbalance of lower - leg muscles , seems to be the initial mechanism causing reduced ankle flexibility and forefoot cavus deformity . 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 22 seems 0 ###LEFT-WALL### 36 . 1 selective 2 denervation 2 denervation 3 of 2 denervation 13 and 3 of 6 musculature 4 intrinsic 5 foot 5 foot 6 musculature 6 musculature 9 of 7 , 8 particularly 7 , 9 of 9 of 11 lumbricals 9 of 12 , 10 the 11 lumbricals 12 , 13 and 13 and 14 not 13 and 15 imbalance 13 and 21 , 13 and 22 seems 15 imbalance 16 of 16 of 20 muscles 17 lower 18 - 17 lower 20 muscles 19 leg 20 muscles 22 seems 23 to 22 seems 24 be 23 to 24 be 24 be 27 mechanism 25 the 27 mechanism 26 initial 27 mechanism 27 mechanism 28 causing 28 causing 32 and 29 reduced 30 ankle 30 ankle 31 flexibility 31 flexibility 32 and 32 and 35 deformity 33 forefoot 34 cavus 34 cavus 35 deformity this study examines whether differences in late - life well - being are linked [to] how older adults encode emotionally valenced information . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 examines 0 ###LEFT-WALL### 23 . 1 this 2 study 2 study 3 examines 3 examines 4 whether 3 examines 16 how 4 whether 5 differences 4 whether 14 linked 5 differences 6 in 5 differences 13 are 6 in 12 being 7 late 10 well 7 late 12 being 8 - 10 well 9 life 10 well 10 well 11 - 13 are 14 linked 16 how 18 adults 16 how 19 encode 17 older 18 adults 18 adults 19 encode 19 encode 22 information 20 emotionally 21 valenced 21 valenced 22 information using fmri with 39 older adults varying in life satisfaction , we examined how viewing positive and negative images would affect activation and connectivity of an emotion - processing network . 0 ###LEFT-WALL### 12 we 0 ###LEFT-WALL### 13 examined 0 ###LEFT-WALL### 28 - 1 using 2 fmri 1 using 11 , 1 using 12 we 2 fmri 3 with 2 fmri 7 varying 3 with 6 adults 4 39 6 adults 5 older 6 adults 7 varying 8 in 8 in 10 satisfaction 9 life 10 satisfaction 12 we 13 examined 13 examined 14 how 14 how 15 viewing 14 how 21 affect 15 viewing 19 images 15 viewing 20 would 16 positive 17 and 17 and 18 negative 17 and 19 images 20 would 21 affect 21 affect 23 and 22 activation 23 and 23 and 24 connectivity 24 connectivity 25 of 25 of 27 emotion 26 an 27 emotion 28 - 30 network 28 - 31 . 29 processing 30 network participants engaged most regions within this network more robustly for positive than for negative images , but within the pfc this effect was moderated by life satisfaction , with individuals higher in satisfaction showing lower levels of activity during the processing of positive images . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 24 moderated 0 ###LEFT-WALL### 28 , 0 ###LEFT-WALL### 45 . 1 participants 2 engaged 2 engaged 4 regions 2 engaged 9 robustly 2 engaged 10 for 3 most 4 regions 4 regions 5 within 5 within 7 network 6 this 7 network 8 more 9 robustly 10 for 22 effect 11 positive 12 than 11 positive 13 for 11 positive 16 , 11 positive 22 effect 13 for 15 images 14 negative 15 images 17 but 18 within 17 but 22 effect 18 within 20 pfc 19 the 20 pfc 21 this 22 effect 22 effect 23 was 23 was 24 moderated 24 moderated 25 by 25 by 27 satisfaction 26 life 27 satisfaction 28 , 35 lower 29 with 30 individuals 29 with 35 lower 30 individuals 31 higher 30 individuals 34 showing 31 higher 32 in 32 in 33 satisfaction 35 lower 36 levels 35 lower 39 during 36 levels 37 of 37 of 38 activity 39 during 41 processing 40 the 41 processing 41 processing 42 of 42 of 44 images 43 positive 44 images participants high in satisfaction showed stronger correlations among network regions - particularly between the amygdala and other emotion processing regions - when viewing positive , as compared [with] negative , images . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 5 showed 0 ###LEFT-WALL### 32 . 1 participants 2 high 1 participants 5 showed 2 high 3 in 3 in 4 satisfaction 5 showed 7 correlations 5 showed 22 when 6 stronger 7 correlations 7 correlations 8 among 7 correlations 13 between 8 among 10 regions 9 network 10 regions 11 - 12 particularly 11 - 13 between 13 between 16 and 13 between 21 - 14 the 15 amygdala 15 amygdala 16 and 16 and 18 emotion 16 and 19 processing 17 other 18 emotion 19 processing 20 regions 22 when 23 viewing 23 viewing 31 images 24 positive 25 , 24 positive 31 images 26 as 27 compared 27 compared 31 images 29 negative 30 , 29 negative 31 images participants low in satisfaction showed no valence effect . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 5 showed 0 ###LEFT-WALL### 9 . 1 participants 2 low 1 participants 5 showed 2 low 3 in 3 in 4 satisfaction 5 showed 7 valence 5 showed 8 effect 6 no 7 valence findings suggest that late - life satisfaction is linked with [how] emotion - processing regions are engaged and connected during processing of valenced information . 0 ###LEFT-WALL### 1 findings 0 ###LEFT-WALL### 2 suggest 0 ###LEFT-WALL### 13 - 1 findings 2 suggest 2 suggest 3 that 3 that 7 satisfaction 3 that 9 linked 4 late 5 - 4 late 6 life 6 life 7 satisfaction 7 satisfaction 8 is 8 is 9 linked 9 linked 10 with 10 with 12 emotion 13 - 15 regions 13 - 18 and 13 - 25 . 14 processing 15 regions 15 regions 16 are 16 are 18 and 17 engaged 18 and 18 and 19 connected 19 connected 20 during 20 during 21 processing 21 processing 22 of 22 of 24 information 23 valenced 24 information this first demonstration of a link between neural [recruitment] and late - life well - being suggests that differences in neural network activation and connectivity may account for the preferential encoding of positive information seen in some older adults . 0 ###LEFT-WALL### 3 demonstration 0 ###LEFT-WALL### 17 suggests 0 ###LEFT-WALL### 40 . 1 this 3 demonstration 2 first 3 demonstration 3 demonstration 4 of 3 demonstration 7 between 3 demonstration 17 suggests 4 of 6 link 5 a 6 link 7 between 10 and 8 neural 10 and 10 and 16 being 11 late 14 well 11 late 15 - 11 late 16 being 12 - 14 well 13 life 14 well 14 well 15 - 17 suggests 18 that 18 that 24 and 18 that 27 account 19 differences 20 in 19 differences 24 and 20 in 23 activation 21 neural 22 network 22 network 23 activation 24 and 25 connectivity 24 and 26 may 26 may 27 account 27 account 28 for 27 account 36 in 28 for 31 encoding 29 the 31 encoding 30 preferential 31 encoding 31 encoding 32 of 31 encoding 35 seen 32 of 34 information 33 positive 34 information 36 in 39 adults 37 some 39 adults 38 older 39 adults background : there is increasing recognition that lower nurse staffing levels are associated with higher morbidity and mortality among medical and surgical patients . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 13 associated 0 ###LEFT-WALL### 24 . 2 : 3 there 2 : 4 is 3 there 4 is 4 is 6 recognition 5 increasing 6 recognition 6 recognition 10 staffing 6 recognition 13 associated 7 that 10 staffing 8 lower 9 nurse 9 nurse 10 staffing 10 staffing 11 levels 10 staffing 12 are 10 staffing 13 associated 11 levels 12 are 13 associated 14 with 13 associated 19 among 14 with 17 and 15 higher 16 morbidity 16 morbidity 17 and 17 and 18 mortality 19 among 23 patients 20 medical 21 and 21 and 22 surgical 21 and 23 patients the degree to which this applies to elderly patients with hip fractures is unclear . 0 ###LEFT-WALL### 2 degree 0 ###LEFT-WALL### 13 is 0 ###LEFT-WALL### 15 . 1 the 2 degree 2 degree 3 to 2 degree 13 is 3 to 4 which 3 to 5 this 3 to 6 applies 5 this 6 applies 6 applies 7 to 6 applies 10 with 7 to 9 patients 8 elderly 9 patients 10 with 12 fractures 11 hip 12 fractures 13 is 14 unclear questions/purposes : we conducted a pilot study using administrative data as an initial step in investigating the relationship between nurse staffing levels and in [-] hospital mortality among elderly patients with hip fractures . 0 ###LEFT-WALL### 1 questions/purposes 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 34 . 2 : 3 we 2 : 4 conducted 3 we 4 conducted 4 conducted 7 study 4 conducted 8 using 4 conducted 15 in 5 a 7 study 6 pilot 7 study 8 using 10 data 8 using 11 as 9 administrative 10 data 11 as 14 step 12 an 14 step 13 initial 14 step 15 in 16 investigating 16 investigating 18 relationship 16 investigating 28 among 16 investigating 31 with 17 the 18 relationship 18 relationship 23 and 19 between 22 levels 19 between 23 and 20 nurse 22 levels 21 staffing 22 levels 23 and 24 in 24 in 27 mortality 26 hospital 27 mortality 28 among 30 patients 29 elderly 30 patients 31 with 33 fractures 32 hip 33 fractures patients and methods : we retrospectively reviewed administrative data for 13,343 patients 65 years or older with a primary diagnosis [of] hip fracture admitted to 39 michigan hospitals between 2003 and 2006 . 0 ###LEFT-WALL### 3 methods 0 ###LEFT-WALL### 4 : 0 ###LEFT-WALL### 33 . 1 patients 2 and 2 and 3 methods 4 : 5 we 4 : 24 admitted 5 we 7 reviewed 6 retrospectively 7 reviewed 7 reviewed 9 data 8 administrative 9 data 9 data 10 for 9 data 15 or 10 for 12 patients 11 13,343 12 patients 13 65 14 years 14 years 15 or 15 or 16 older 16 older 17 with 17 with 23 fracture 17 with 24 admitted 18 a 23 fracture 19 primary 22 hip 20 diagnosis 22 hip 22 hip 23 fracture 24 admitted 25 to 24 admitted 29 between 25 to 28 hospitals 26 39 28 hospitals 27 michigan 28 hospitals 29 between 31 and 30 2003 31 and 31 and 32 2006 we used logistic regression to calculate the change in predicted probability of in - hospital death conferred by differences in the hospitals ' overall number of full - time equivalent registered nursing staff ( fte - rn ) per patient day . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 used 0 ###LEFT-WALL### 14 - 0 ###LEFT-WALL### 42 . 1 we 2 used 2 used 4 regression 3 logistic 4 regression 4 regression 5 to 4 regression 13 in 5 to 6 calculate 6 calculate 8 change 7 the 8 change 8 change 9 in 8 change 12 of 9 in 11 probability 10 predicted 11 probability 12 of 13 in 14 - 16 death 15 hospital 16 death 16 death 17 conferred 16 death 20 in 17 conferred 18 by 18 by 19 differences 20 in 25 number 21 the 22 hospitals 22 hospitals 23 ' 23 ' 25 number 24 overall 25 number 25 number 26 of 25 number 39 per 26 of 33 staff 27 full 28 - 27 full 32 nursing 29 time 30 equivalent 30 equivalent 31 registered 31 registered 32 nursing 32 nursing 33 staff 33 staff 37 rn 34 ( 37 rn 35 fte 37 rn 36 - 37 rn 37 rn 38 ) 39 per 41 day 40 patient 41 day regression models controlled for patient age , gender , and comorbid conditions ; hospital characteristics including teaching status , hip fracture volume , and income/racial composition of the hospital 's zip code ; [and] seasonal influenza . 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 13 ; 0 ###LEFT-WALL### 37 . 1 regression 2 models 2 models 3 controlled 2 models 4 for 2 models 7 , 4 for 6 age 5 patient 6 age 7 , 8 gender 7 , 10 and 9 , 10 and 10 and 12 conditions 11 comorbid 12 conditions 13 ; 24 and 13 ; 33 ; 14 hospital 15 characteristics 15 characteristics 16 including 15 characteristics 24 and 16 including 18 status 17 teaching 18 status 18 status 22 volume 19 , 22 volume 20 hip 21 fracture 21 fracture 22 volume 22 volume 23 , 23 , 24 and 24 and 26 composition 25 income/racial 26 composition 26 composition 27 of 27 of 32 code 28 the 29 hospital 29 hospital 30 's 30 's 32 code 31 zip 32 code 33 ; 36 influenza 35 seasonal 36 influenza results : we found an association between hospital [-] wide nurse staffing levels and in [-] hospital mortality among patients with hip fractures . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 3 we 2 : 4 found 2 : 24 . 3 we 4 found 4 found 6 association 4 found 19 among 5 an 6 association 6 association 14 and 7 between 13 levels 7 between 14 and 8 hospital 13 levels 10 wide 11 nurse 11 nurse 13 levels 12 staffing 13 levels 14 and 15 in 15 in 18 mortality 17 hospital 18 mortality 19 among 20 patients 20 patients 21 with 21 with 23 fractures 22 hip 23 fractures the odds of in [-] hospital mortality decreased by 0.16 for every additional fte - rn added per patient day , even after controlling for covariates . 0 ###LEFT-WALL### 2 odds 0 ###LEFT-WALL### 21 , 0 ###LEFT-WALL### 27 . 1 the 2 odds 2 odds 3 of 2 odds 21 , 3 of 4 in 4 in 7 mortality 6 hospital 7 mortality 8 decreased 9 by 8 decreased 21 , 9 by 10 0.16 10 0.16 11 for 10 0.16 17 added 10 0.16 18 per 11 for 16 rn 12 every 16 rn 13 additional 16 rn 14 fte 16 rn 15 - 16 rn 18 per 20 day 19 patient 20 day 21 , 22 even 22 even 23 after 23 after 24 controlling 24 controlling 25 for 25 for 26 covariates this association suggests the absolute risk of mortality increases by 0.35 percentage points for every one unit decrease of fte - rn per patient day , a 16 % increase in the risk of death . 0 ###LEFT-WALL### 2 association 0 ###LEFT-WALL### 3 suggests 1 this 2 association 2 association 3 suggests 3 suggests 6 risk 3 suggests 9 increases 4 the 6 risk 5 absolute 6 risk 6 risk 7 of 6 risk 9 increases 7 of 8 mortality 9 increases 10 by 9 increases 18 decrease 10 by 13 points 11 0.35 13 points 12 percentage 13 points 13 points 14 for 14 for 16 one 15 every 16 one 17 unit 18 decrease 18 decrease 19 of 18 decrease 23 per 18 decrease 30 increase 19 of 22 rn 20 fte 22 rn 21 - 22 rn 23 per 25 day 24 patient 25 day 26 , 30 increase 27 a 30 increase 28 16 29 % 29 % 30 increase 30 increase 31 in 30 increase 36 . 31 in 33 risk 32 the 33 risk 33 risk 34 of 34 of 35 death conclusions : decreased hospital - wide nurse staffing levels are associated with increased in [-] hospital mortality among patients admitted with hip fractures . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 4 hospital 2 : 5 - 3 decreased 4 hospital 5 - 8 staffing 5 - 13 increased 5 - 24 . 6 wide 7 nurse 7 nurse 8 staffing 8 staffing 9 levels 8 staffing 12 with 8 staffing 13 increased 9 levels 10 are 10 are 11 associated 11 associated 12 with 13 increased 14 in 14 in 17 mortality 16 hospital 17 mortality 17 mortality 18 among 17 mortality 20 admitted 17 mortality 21 with 18 among 19 patients 21 with 23 fractures 22 hip 23 fractures these observations indicate the need for further studies to characterize this relationship for staffing of units caring for patients with hip fractures . 0 ###LEFT-WALL### 2 observations 0 ###LEFT-WALL### 3 indicate 0 ###LEFT-WALL### 23 . 1 these 2 observations 2 observations 3 indicate 3 indicate 5 need 4 the 5 need 5 need 6 for 5 need 9 to 5 need 10 characterize 6 for 8 studies 7 further 8 studies 9 to 10 characterize 10 characterize 12 relationship 10 characterize 13 for 10 characterize 20 with 11 this 12 relationship 13 for 14 staffing 14 staffing 15 of 14 staffing 17 caring 15 of 16 units 17 caring 18 for 18 for 19 patients 20 with 22 fractures 21 hip 22 fractures level of evidence : level iii , prognostic 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 iii 7 , 9 study 8 prognostic 9 study see guidelines for authors for a complete description of levels of evidence . 0 ###LEFT-WALL### 1 see 0 ###LEFT-WALL### 13 . 1 see 2 guidelines 2 guidelines 3 for 3 for 4 authors 4 authors 5 for 5 for 8 description 6 a 7 complete 6 a 8 description 7 complete 8 description 8 description 9 of 9 of 10 levels 10 levels 11 of 11 of 12 evidence we examined the individual association [between] body mass index ( bmi ) and sleep [quality] among the very elderly . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 20 . 1 we 13 and 2 examined 9 index 2 examined 13 and 3 the 9 index 4 individual 5 association 5 association 9 index 7 body 9 index 8 mass 9 index 9 index 11 bmi 10 ( 11 bmi 11 bmi 12 ) 13 and 14 sleep 13 and 16 among 16 among 19 elderly 17 the 18 very 17 the 19 elderly the present study analyzed data from [survey] that was conducted on all residents aged 90 years or more in a district , there were 2,311,709 inhabitants in 2005 . 0 ###LEFT-WALL### 3 study 0 ###LEFT-WALL### 4 analyzed 0 ###LEFT-WALL### 22 , 0 ###LEFT-WALL### 24 were 0 ###LEFT-WALL### 29 . 1 the 3 study 2 present 3 study 3 study 4 analyzed 4 analyzed 5 data 4 analyzed 10 conducted 5 data 6 from 5 data 9 was 6 from 8 that 9 was 10 conducted 10 conducted 11 on 10 conducted 14 aged 11 on 13 residents 12 all 13 residents 14 aged 17 or 14 aged 19 in 15 90 16 years 16 years 17 or 17 or 18 more 19 in 21 district 20 a 21 district 22 , 23 there 22 , 24 were 23 there 24 were 24 were 26 inhabitants 25 2,311,709 26 inhabitants 26 inhabitants 27 in 27 in 28 2005 sleep quality was measured using the pittsburgh sleep quality index ( psqi ) . 0 ###LEFT-WALL### 2 quality 0 ###LEFT-WALL### 3 was 0 ###LEFT-WALL### 14 . 1 sleep 2 quality 2 quality 3 was 3 was 4 measured 4 measured 5 using 5 using 12 psqi 6 the 7 pittsburgh 7 pittsburgh 8 sleep 8 sleep 9 quality 9 quality 10 index 10 index 12 psqi 11 ( 12 psqi 12 psqi 13 ) sleep quality included quality classification and scores , sleep duration , sleep latency , and sleep efficiency . 0 ###LEFT-WALL### 2 quality 0 ###LEFT-WALL### 6 and 0 ###LEFT-WALL### 8 , 0 ###LEFT-WALL### 18 . 1 sleep 2 quality 2 quality 6 and 3 included 5 classification 3 included 6 and 4 quality 5 classification 6 and 7 scores 8 , 15 and 9 sleep 10 duration 10 duration 11 , 11 , 13 latency 11 , 15 and 12 sleep 13 latency 14 , 15 and 15 and 17 efficiency 16 sleep 17 efficiency the subjects included in the statistical analysis were 216 men and 444 women . 0 ###LEFT-WALL### 2 subjects 0 ###LEFT-WALL### 8 were 0 ###LEFT-WALL### 14 . 1 the 2 subjects 2 subjects 3 included 2 subjects 8 were 3 included 4 in 4 in 7 analysis 5 the 7 analysis 6 statistical 7 analysis 8 were 11 and 9 216 10 men 10 men 11 and 11 and 13 women 12 444 13 women according to quartile of bmi or classification criteria of underweight , normal weight , overweight , and obesity in bmi , none of the differences in sleep quality scores , sleep latency , sleep duration , sleep efficiency percentage , and prevalence of poor sleep quality was significant among different bmi groups . 0 ###LEFT-WALL### 25 differences 0 ###LEFT-WALL### 30 , 0 ###LEFT-WALL### 53 . 1 according 2 to 2 to 3 quartile 2 to 21 , 2 to 25 differences 3 quartile 4 of 3 quartile 9 of 3 quartile 17 and 4 of 6 or 5 bmi 6 or 6 or 8 criteria 7 classification 8 criteria 9 of 13 weight 10 underweight 11 , 10 underweight 13 weight 12 normal 13 weight 14 , 17 and 15 overweight 17 and 16 , 17 and 17 and 18 obesity 17 and 19 in 17 and 21 , 19 in 20 bmi 22 none 23 of 22 none 25 differences 23 of 25 differences 24 the 25 differences 25 differences 26 in 25 differences 30 , 26 in 28 quality 27 sleep 28 quality 29 scores 30 , 30 , 31 sleep 30 , 41 and 32 latency 33 , 33 , 35 duration 33 , 36 , 34 sleep 35 duration 36 , 39 percentage 36 , 41 and 37 sleep 39 percentage 38 efficiency 39 percentage 40 , 41 and 41 and 42 prevalence 41 and 43 of 41 and 51 bmi 41 and 52 groups 43 of 45 sleep 44 poor 45 sleep 45 sleep 46 quality 45 sleep 49 among 46 quality 47 was 47 was 48 significant 48 significant 49 among 50 different 51 bmi 51 bmi 52 groups the difference in bmi between subjects with good and poor sleep quality was [non] [-] significant . 0 ###LEFT-WALL### 2 difference 0 ###LEFT-WALL### 13 was 0 ###LEFT-WALL### 17 . 1 the 2 difference 2 difference 3 in 2 difference 13 was 3 in 4 bmi 4 bmi 5 between 5 between 6 subjects 6 subjects 7 with 7 with 12 quality 8 good 9 and 9 and 10 poor 9 and 11 sleep 11 sleep 12 quality 13 was 16 significant unadjusted and adjusted multiple logistic regression showed that none of the bmi groups had a function of decreasing the risk for poor quality . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 7 showed 0 ###LEFT-WALL### 24 . 1 unadjusted 2 and 2 and 6 regression 2 and 7 showed 3 adjusted 4 multiple 4 multiple 6 regression 5 logistic 6 regression 7 showed 8 that 8 that 13 groups 8 that 14 had 9 none 10 of 9 none 13 groups 10 of 13 groups 11 the 13 groups 12 bmi 13 groups 13 groups 14 had 14 had 16 function 14 had 21 for 15 a 16 function 16 function 17 of 17 of 18 decreasing 18 decreasing 20 risk 19 the 20 risk 21 for 23 quality 22 poor 23 quality among longevity chinese , there is no association between bmi and sleep quality . 0 ###LEFT-WALL### 5 there 0 ###LEFT-WALL### 6 is 0 ###LEFT-WALL### 14 . 1 among 3 chinese 1 among 4 , 1 among 5 there 2 longevity 3 chinese 5 there 6 is 6 is 8 association 6 is 9 between 7 no 8 association 9 between 11 and 10 bmi 11 and 11 and 13 quality 12 sleep 13 quality it is currently estimated that infections and inflammatory responses are linked to 15 - 20 % of all deaths from cancer worldwide . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 4 estimated 0 ###LEFT-WALL### 23 . 1 it 2 is 2 is 3 currently 2 is 4 estimated 4 estimated 5 that 5 that 7 and 5 that 11 linked 6 infections 7 and 7 and 9 responses 7 and 10 are 8 inflammatory 9 responses 10 are 11 linked 11 linked 12 to 11 linked 22 worldwide 12 to 16 % 13 15 14 - 14 - 15 20 14 - 16 % 16 % 17 of 17 of 19 deaths 18 all 19 deaths 19 deaths 20 from 20 from 21 cancer many studies point to an important role of inflammation in prostate growth , although the contribution of inflammation to benign prostatic hyperplasia and prostate cancer is not completely understood . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 3 point 0 ###LEFT-WALL### 13 , 0 ###LEFT-WALL### 30 . 1 many 2 studies 2 studies 3 point 3 point 4 to 3 point 10 in 4 to 7 role 5 an 6 important 5 an 7 role 6 important 7 role 7 role 8 of 8 of 9 inflammation 10 in 12 growth 11 prostate 12 growth 13 , 25 cancer 13 , 29 understood 14 although 16 contribution 14 although 25 cancer 15 the 16 contribution 16 contribution 17 of 16 contribution 19 to 17 of 18 inflammation 19 to 23 and 20 benign 22 hyperplasia 21 prostatic 22 hyperplasia 22 hyperplasia 23 and 23 and 24 prostate 25 cancer 26 is 26 is 27 not 26 is 29 understood 28 completely 29 understood there is an unmet need for epidemiologic and molecular pathologic approaches to address the issue of inflammation and prostate cancer . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 21 . 1 there 2 is 2 is 5 need 3 an 5 need 4 unmet 5 need 5 need 6 for 5 need 12 to 5 need 13 address 5 need 16 of 6 for 11 approaches 7 epidemiologic 8 and 8 and 9 molecular 8 and 11 approaches 10 pathologic 11 approaches 12 to 13 address 13 address 15 issue 14 the 15 issue 16 of 18 and 17 inflammation 18 and 18 and 20 cancer 19 prostate 20 cancer here we review the published evidence with respect to the involvement of inflammation and infection in prostate cancer . 0 ###LEFT-WALL### 2 we 0 ###LEFT-WALL### 3 review 0 ###LEFT-WALL### 19 . 1 here 2 we 2 we 3 review 3 review 6 evidence 3 review 7 with 3 review 9 to 3 review 16 in 4 the 6 evidence 5 published 6 evidence 7 with 8 respect 9 to 11 involvement 10 the 11 involvement 11 involvement 12 of 12 of 14 and 13 inflammation 14 and 14 and 15 infection 16 in 18 cancer 17 prostate 18 cancer we also present an overarching hypothesis that chronic inflammation associated with aging and infection may play an important role in the etiology and progression of prostate cancer . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 28 . 1 we 13 and 2 also 3 present 3 present 6 hypothesis 3 present 11 with 3 present 13 and 4 an 6 hypothesis 5 overarching 6 hypothesis 6 hypothesis 7 that 6 hypothesis 10 associated 7 that 9 inflammation 7 that 10 associated 8 chronic 9 inflammation 9 inflammation 10 associated 11 with 12 aging 13 and 16 play 14 infection 15 may 15 may 16 play 16 play 19 role 16 play 20 in 17 an 18 important 17 an 19 role 18 important 19 role 20 in 23 and 21 the 22 etiology 22 etiology 23 and 23 and 24 progression 23 and 25 of 25 of 27 cancer 26 prostate 27 cancer as such [,] chronic inflammation may represent an important therapeutic target in prostate cancer . 0 ###LEFT-WALL### 7 represent 0 ###LEFT-WALL### 15 . 1 as 5 inflammation 1 as 6 may 1 as 7 represent 2 such 5 inflammation 4 chronic 5 inflammation 5 inflammation 6 may 7 represent 11 target 7 represent 12 in 8 an 9 important 8 an 11 target 9 important 11 target 10 therapeutic 11 target 12 in 14 cancer 13 prostate 14 cancer much of our daily communication occurs in the presence of background noise , compromising our ability to hear . 0 ###LEFT-WALL### 5 communication 0 ###LEFT-WALL### 6 occurs 1 much 2 of 1 much 5 communication 2 of 5 communication 3 our 5 communication 4 daily 5 communication 5 communication 6 occurs 6 occurs 7 in 7 in 9 presence 8 the 9 presence 9 presence 10 of 10 of 12 noise 11 background 12 noise 12 noise 14 compromising 13 , 14 compromising 14 compromising 16 ability 14 compromising 19 . 15 our 16 ability 16 ability 17 to 16 ability 18 hear 17 to 18 hear while understanding speech in noise is a challenge for everyone , it becomes [increasingly] difficult as [we] age . 0 ###LEFT-WALL### 12 it 0 ###LEFT-WALL### 13 becomes 0 ###LEFT-WALL### 19 . 1 while 2 understanding 1 while 6 is 1 while 11 , 1 while 12 it 2 understanding 3 speech 2 understanding 6 is 3 speech 4 in 4 in 5 noise 6 is 8 challenge 7 a 8 challenge 8 challenge 9 for 9 for 10 everyone 12 it 13 becomes 13 becomes 15 difficult 15 difficult 16 as 16 as 18 age although aging is generally accompanied by hearing loss , this perceptual decline cannot fully account for the difficulties experienced by older adults for hearing in noise . 0 ###LEFT-WALL### 12 decline 0 ###LEFT-WALL### 15 account 0 ###LEFT-WALL### 27 . 1 although 2 aging 1 although 5 accompanied 1 although 9 , 1 although 12 decline 2 aging 3 is 3 is 5 accompanied 4 generally 5 accompanied 5 accompanied 6 by 6 by 7 hearing 7 hearing 8 loss 10 this 12 decline 11 perceptual 12 decline 12 decline 13 cannot 13 cannot 15 account 14 fully 15 account 15 account 16 for 16 for 18 difficulties 17 the 18 difficulties 18 difficulties 19 experienced 18 difficulties 23 for 19 experienced 20 by 20 by 22 adults 21 older 22 adults 23 for 24 hearing 24 hearing 25 in 25 in 26 noise decreased cognitive skills concurrent with reduced perceptual acuity are thought to contribute to the difficulty older adults experience understanding speech in noise . 0 ###LEFT-WALL### 3 skills 0 ###LEFT-WALL### 10 thought 0 ###LEFT-WALL### 23 . 1 decreased 3 skills 2 cognitive 3 skills 3 skills 4 concurrent 3 skills 9 are 4 concurrent 5 with 5 with 8 acuity 6 reduced 8 acuity 7 perceptual 8 acuity 9 are 10 thought 10 thought 11 to 10 thought 17 adults 10 thought 18 experience 11 to 12 contribute 12 contribute 13 to 13 to 15 difficulty 14 the 15 difficulty 16 older 17 adults 17 adults 18 experience 18 experience 20 speech 18 experience 21 in 19 understanding 20 speech 21 in 22 noise given that musical experience positively impacts speech perception in noise in young adults ( ages 18 - 30 ) , we asked whether musical experience benefits an older cohort of musicians ( ages 45 - 65 ) , potentially offsetting the age - related decline in [speech] - in - noise perceptual abilities and associated cognitive function ( i.e [.] , working memory ) . 1 given 4 experience 2 that 3 musical 3 musical 4 experience 4 experience 6 impacts 5 positively 6 impacts 6 impacts 8 perception 6 impacts 9 in 7 speech 8 perception 9 in 10 noise 10 noise 11 in 10 noise 21 we 10 noise 22 asked 11 in 13 adults 12 young 13 adults 13 adults 15 ages 14 ( 15 ages 15 ages 16 18 15 ages 18 30 15 ages 20 , 17 - 18 30 18 30 19 ) 21 we 22 asked 22 asked 23 whether 23 whether 25 experience 23 whether 26 benefits 24 musical 25 experience 25 experience 26 benefits 26 benefits 29 cohort 27 an 29 cohort 28 older 29 cohort 29 cohort 30 of 29 cohort 40 offsetting 30 of 31 musicians 31 musicians 33 ages 32 ( 33 ages 33 ages 34 45 33 ages 36 65 33 ages 38 , 35 - 36 65 36 65 37 ) 39 potentially 40 offsetting 40 offsetting 42 age 41 the 42 age 42 age 45 decline 42 age 54 and 43 - 45 decline 44 related 45 decline 45 decline 46 in 45 decline 50 - 46 in 49 in 48 - 49 in 50 - 54 and 51 noise 53 abilities 52 perceptual 53 abilities 53 abilities 54 and 54 and 57 function 54 and 59 i.e 54 and 65 . 55 associated 57 function 56 cognitive 57 function 58 ( 59 i.e 59 i.e 63 memory 59 i.e 65 . 61 , 63 memory 62 working 63 memory 63 memory 64 ) consistent with performance in young adults , older musicians demonstrated enhanced speech - in [-] noise perception relative to nonmusicians along with greater auditory , but not visual , working memory capacity . 0 ###LEFT-WALL### 9 musicians 0 ###LEFT-WALL### 11 enhanced 1 consistent 2 with 1 consistent 4 in 1 consistent 7 , 1 consistent 9 musicians 2 with 3 performance 4 in 6 adults 5 young 6 adults 8 older 9 musicians 9 musicians 10 demonstrated 9 musicians 11 enhanced 11 enhanced 12 speech 12 speech 14 in 13 - 14 in 14 in 17 perception 14 in 33 . 16 noise 17 perception 17 perception 18 relative 18 relative 19 to 18 relative 22 with 19 to 20 nonmusicians 21 along 22 with 22 with 32 capacity 23 greater 31 memory 24 auditory 26 but 25 , 26 but 26 but 27 not 26 but 30 working 26 but 31 memory 27 not 28 visual 28 visual 29 , 28 visual 30 working 31 memory 32 capacity by demonstrating that speech [-] in [-] noise perception and related cognitive function are enhanced in older musicians , our results imply that musical training may reduce the impact of age - related auditory decline . 0 ###LEFT-WALL### 21 results 0 ###LEFT-WALL### 22 imply 0 ###LEFT-WALL### 32 - 0 ###LEFT-WALL### 36 . 1 by 2 demonstrating 1 by 19 , 1 by 21 results 2 demonstrating 3 that 3 that 10 and 3 that 15 enhanced 4 speech 6 in 4 speech 10 and 6 in 9 perception 8 noise 9 perception 10 and 13 function 10 and 14 are 11 related 13 function 12 cognitive 13 function 14 are 15 enhanced 15 enhanced 16 in 16 in 18 musicians 17 older 18 musicians 20 our 21 results 21 results 22 imply 22 imply 23 that 23 that 25 training 23 that 27 reduce 24 musical 25 training 25 training 26 may 26 may 27 reduce 27 reduce 29 impact 28 the 29 impact 29 impact 30 of 30 of 31 age 32 - 35 decline 33 related 35 decline 34 auditory 35 decline ageing is driven by the inexorable and stochastic accumulation of damage in biomolecules vital [for] proper cellular function . 0 ###LEFT-WALL### 1 ageing 0 ###LEFT-WALL### 3 driven 0 ###LEFT-WALL### 19 . 1 ageing 2 is 2 is 3 driven 3 driven 4 by 4 by 18 function 5 the 18 function 6 inexorable 7 and 7 and 9 accumulation 7 and 10 of 7 and 18 function 8 stochastic 9 accumulation 10 of 11 damage 11 damage 12 in 12 in 13 biomolecules 14 vital 18 function 16 proper 18 function 17 cellular 18 function although this process is fundamentally haphazard and uncontrollable , senescent decline and ageing is broadly influenced by genetic and extrinsic factors . 0 ###LEFT-WALL### 3 process 0 ###LEFT-WALL### 4 is 0 ###LEFT-WALL### 9 , 0 ###LEFT-WALL### 22 . 1 although 2 this 1 although 3 process 3 process 4 is 4 is 5 fundamentally 4 is 7 and 6 haphazard 7 and 7 and 8 uncontrollable 9 , 11 decline 9 , 12 and 10 senescent 11 decline 12 and 13 ageing 12 and 16 influenced 13 ageing 14 is 14 is 15 broadly 14 is 16 influenced 16 influenced 17 by 17 by 21 factors 18 genetic 19 and 19 and 20 extrinsic 19 and 21 factors numerous gene mutations and treatments have been shown to extend the lifespan of diverse organisms ranging from the unicellular saccharomyces cerevisiae to primates . 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 8 shown 0 ###LEFT-WALL### 24 . 1 numerous 2 gene 2 gene 3 mutations 3 mutations 4 and 4 and 5 treatments 4 and 6 have 6 have 7 been 7 been 8 shown 8 shown 9 to 8 shown 17 from 8 shown 22 to 9 to 10 extend 10 extend 12 lifespan 11 the 12 lifespan 12 lifespan 13 of 13 of 15 organisms 14 diverse 15 organisms 15 organisms 16 ranging 17 from 21 cerevisiae 18 the 21 cerevisiae 19 unicellular 21 cerevisiae 20 saccharomyces 21 cerevisiae 22 to 23 primates it is [becoming] increasingly apparent that most such interventions ultimately interface with cellular stress response mechanisms , suggesting that longevity is intimately related to the ability of the organism to effectively cope with both intrinsic and extrinsic stress . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 38 stress 0 ###LEFT-WALL### 39 . 1 it 2 is 2 is 4 increasingly 2 is 5 apparent 5 apparent 6 that 6 that 7 most 6 that 38 stress 7 most 9 interventions 7 most 11 interface 7 most 38 stress 8 such 9 interventions 9 interventions 11 interface 10 ultimately 11 interface 11 interface 12 with 12 with 16 mechanisms 13 cellular 16 mechanisms 14 stress 16 mechanisms 15 response 16 mechanisms 17 , 23 related 18 suggesting 20 longevity 18 suggesting 21 is 18 suggesting 23 related 19 that 20 longevity 20 longevity 21 is 21 is 22 intimately 23 related 24 to 23 related 33 with 23 related 36 and 23 related 38 stress 24 to 26 ability 25 the 26 ability 26 ability 27 of 26 ability 30 to 26 ability 32 cope 27 of 29 organism 28 the 29 organism 30 to 32 cope 31 effectively 32 cope 33 with 34 both 35 intrinsic 36 and 36 and 37 extrinsic here , we survey the molecular mechanisms that link ageing to main stress response pathways , and mediate age - related changes in the effectiveness of the response to stress . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 21 related 1 here 2 , 1 here 3 we 3 we 17 and 4 survey 7 mechanisms 4 survey 11 to 4 survey 17 and 5 the 7 mechanisms 6 molecular 7 mechanisms 7 mechanisms 8 that 7 mechanisms 9 link 8 that 9 link 9 link 10 ageing 11 to 15 pathways 12 main 13 stress 13 stress 15 pathways 14 response 15 pathways 16 , 17 and 17 and 18 mediate 18 mediate 19 age 20 - 21 related 21 related 22 changes 21 related 23 in 21 related 29 to 21 related 31 . 23 in 25 effectiveness 24 the 25 effectiveness 25 effectiveness 26 of 26 of 28 response 27 the 28 response 29 to 30 stress we also discuss how each pathway contributes to modulate the ageing process . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 discuss 0 ###LEFT-WALL### 13 . 1 we 3 discuss 2 also 3 discuss 3 discuss 4 how 4 how 6 pathway 4 how 7 contributes 5 each 6 pathway 6 pathway 7 contributes 7 contributes 8 to 8 to 9 modulate 9 modulate 12 process 10 the 12 process 11 ageing 12 process a better understanding of the dynamics and reciprocal interplay between stress responses and ageing is critical for the development of novel therapeutic strategies that exploit endogenous stress combat pathways against age - associated pathologies . 0 ###LEFT-WALL### 3 understanding 0 ###LEFT-WALL### 15 is 0 ###LEFT-WALL### 32 - 0 ###LEFT-WALL### 35 . 1 a 3 understanding 2 better 3 understanding 3 understanding 4 of 3 understanding 10 between 3 understanding 15 is 4 of 7 and 5 the 6 dynamics 6 dynamics 7 and 7 and 9 interplay 8 reciprocal 9 interplay 10 between 13 and 11 stress 12 responses 12 responses 13 and 13 and 14 ageing 15 is 16 critical 16 critical 17 for 16 critical 20 of 16 critical 30 against 17 for 19 development 18 the 19 development 20 of 23 strategies 21 novel 23 strategies 22 therapeutic 23 strategies 23 strategies 24 that 23 strategies 25 exploit 24 that 25 exploit 25 exploit 29 pathways 26 endogenous 29 pathways 27 stress 29 pathways 28 combat 29 pathways 30 against 31 age 32 - 34 pathologies 33 associated 34 pathologies background : oronasal fistulas after oromaxillary surgery may sometimes be encountered and remain a challenging problem . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 17 . 1 background 2 : 2 : 4 fistulas 2 : 5 after 3 oronasal 4 fistulas 5 after 7 surgery 5 after 12 and 6 oromaxillary 7 surgery 7 surgery 8 may 8 may 12 and 9 sometimes 10 be 10 be 11 encountered 10 be 12 and 12 and 13 remain 13 remain 16 problem 14 a 16 problem 15 challenging 16 problem they can cause significant disabilities such as phonetic problems and food or liquid regurgitation while swallowing . 0 ###LEFT-WALL### 1 they 0 ###LEFT-WALL### 3 cause 0 ###LEFT-WALL### 17 . 1 they 2 can 2 can 3 cause 3 cause 5 disabilities 3 cause 15 while 4 significant 5 disabilities 5 disabilities 7 as 6 such 7 as 7 as 12 or 8 phonetic 9 problems 9 problems 10 and 10 and 11 food 10 and 12 or 12 or 14 regurgitation 13 liquid 14 regurgitation 15 while 16 swallowing a few methods are reported to solve this problem , including using a dental appliance , local tissue rotation , or even free - tissue transfer . 0 ###LEFT-WALL### 3 methods 0 ###LEFT-WALL### 5 reported 1 a 2 few 2 few 3 methods 3 methods 4 are 4 are 5 reported 5 reported 6 to 5 reported 7 solve 6 to 7 solve 7 solve 9 problem 7 solve 11 including 8 this 9 problem 10 , 11 including 11 including 12 using 11 including 26 transfer 11 including 27 . 12 using 21 or 13 a 15 appliance 14 dental 15 appliance 15 appliance 16 , 16 , 19 rotation 16 , 21 or 17 local 19 rotation 18 tissue 19 rotation 20 , 21 or 21 or 25 tissue 22 even 25 tissue 23 free 24 - 23 free 25 tissue materials and methods : an angular artery cutaneous flap was designed to repair the defect . 0 ###LEFT-WALL### 3 methods 0 ###LEFT-WALL### 4 : 1 materials 2 and 2 and 3 methods 4 : 9 flap 4 : 11 designed 4 : 16 . 5 an 6 angular 5 an 9 flap 6 angular 7 artery 7 artery 9 flap 8 cutaneous 9 flap 9 flap 10 was 10 was 11 designed 11 designed 12 to 11 designed 13 repair 12 to 13 repair 13 repair 15 defect 14 the 15 defect the flap that included the skin and superficial fascia fed by the flow of angular artery was rotated through the buccal mucosa into the oral cavity to cover the palate defect . 0 ###LEFT-WALL### 2 flap 0 ###LEFT-WALL### 18 rotated 0 ###LEFT-WALL### 32 . 1 the 2 flap 2 flap 3 that 2 flap 4 included 2 flap 17 was 3 that 4 included 4 included 16 artery 5 the 16 artery 6 skin 7 and 7 and 8 superficial 7 and 9 fascia 7 and 14 of 7 and 16 artery 9 fascia 10 fed 10 fed 11 by 11 by 13 flow 12 the 13 flow 13 flow 14 of 15 angular 16 artery 17 was 18 rotated 18 rotated 19 through 18 rotated 23 into 18 rotated 27 to 19 through 22 mucosa 20 the 22 mucosa 21 buccal 22 mucosa 23 into 26 cavity 24 the 26 cavity 25 oral 26 cavity 27 to 28 cover 28 cover 31 defect 29 the 31 defect 30 palate 31 defect case reports : two oronasal fistula cases were reported in this series . 0 ###LEFT-WALL### 2 reports 0 ###LEFT-WALL### 3 : 1 case 2 reports 3 : 7 cases 3 : 9 reported 3 : 13 . 4 two 7 cases 5 oronasal 6 fistula 6 fistula 7 cases 7 cases 8 were 8 were 9 reported 9 reported 10 in 10 in 12 series 11 this 12 series case 1 : a 71 [-] year [-] old man had hard palate cancer and had received wide excision in our hospital 2 years previously . 0 ###LEFT-WALL### 1 case 0 ###LEFT-WALL### 16 had 0 ###LEFT-WALL### 26 . 1 case 2 1 1 case 3 : 3 : 10 man 4 a 10 man 5 71 7 year 7 year 10 man 9 old 10 man 10 man 15 and 11 had 14 cancer 11 had 15 and 12 hard 13 palate 13 palate 14 cancer 15 and 16 had 16 had 19 excision 16 had 25 previously 17 received 19 excision 18 wide 19 excision 19 excision 20 in 20 in 24 years 21 our 24 years 22 hospital 24 years 23 2 24 years he had received adjuvant radiotherapy ( 28 times ) and was transferred to the plastic surgery department for dealing [with] oronasal [fistula] . 0 ###LEFT-WALL### 1 he 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 23 . 1 he 10 and 2 had 3 received 2 had 10 and 3 received 5 radiotherapy 4 adjuvant 5 radiotherapy 5 radiotherapy 8 times 6 ( 8 times 7 28 8 times 8 times 9 ) 10 and 11 was 11 was 12 transferred 12 transferred 13 to 12 transferred 18 for 12 transferred 21 oronasal 13 to 17 department 14 the 17 department 15 plastic 16 surgery 16 surgery 17 department 18 for 19 dealing the palate defect was 2 × [2] cm . 0 ###LEFT-WALL### 3 defect 0 ###LEFT-WALL### 4 was 0 ###LEFT-WALL### 9 . 1 the 3 defect 2 palate 3 defect 3 defect 4 was 4 was 8 cm 5 2 8 cm 6 × 8 cm case 2 : a 72 [-] year [-] old woman was a patient with left palate mucoepidermoid carcinoma . 0 ###LEFT-WALL### 1 case 0 ###LEFT-WALL### 3 : 0 ###LEFT-WALL### 19 . 1 case 2 2 3 : 10 woman 3 : 11 was 4 a 10 woman 5 72 7 year 7 year 10 woman 9 old 10 woman 10 woman 11 was 11 was 13 patient 12 a 13 patient 13 patient 14 with 14 with 18 carcinoma 15 left 16 palate 16 palate 18 carcinoma 17 mucoepidermoid 18 carcinoma she had received an operation and adjuvant radiotherapy 10 years previously . 0 ###LEFT-WALL### 1 she 0 ###LEFT-WALL### 3 received 0 ###LEFT-WALL### 12 . 1 she 2 had 2 had 3 received 3 received 10 years 3 received 11 previously 4 an 5 operation 5 operation 6 and 6 and 8 radiotherapy 6 and 10 years 7 adjuvant 8 radiotherapy 8 radiotherapy 9 10 for her oronasal fistula and hypernasality , she had received reconstructive operations 3 times with local rotation flap for left - side [palate] [defect] at a previous hospital . 0 ###LEFT-WALL### 8 she 0 ###LEFT-WALL### 10 received 0 ###LEFT-WALL### 21 - 1 for 5 and 1 for 7 , 1 for 8 she 2 her 4 fistula 3 oronasal 4 fistula 4 fistula 5 and 5 and 6 hypernasality 8 she 9 had 9 had 10 received 10 received 12 operations 10 received 20 left 11 reconstructive 12 operations 12 operations 13 3 12 operations 14 times 12 operations 19 for 14 times 15 with 14 times 18 flap 15 with 17 rotation 16 local 17 rotation 18 flap 19 for 21 - 22 side 21 - 29 . 22 side 25 at 25 at 28 hospital 26 a 28 hospital 27 previous 28 hospital however , the local flap failed and the fistula persisted . 0 ###LEFT-WALL### 7 and 0 ###LEFT-WALL### 10 persisted 0 ###LEFT-WALL### 11 . 1 however 2 , 1 however 7 and 3 the 5 flap 4 local 5 flap 5 flap 6 failed 5 flap 7 and 7 and 9 fistula 7 and 10 persisted 8 the 9 fistula she then approached our plastic surgery department for help . 0 ###LEFT-WALL### 1 she 0 ###LEFT-WALL### 3 approached 0 ###LEFT-WALL### 10 . 1 she 3 approached 2 then 3 approached 3 approached 7 department 4 our 7 department 5 plastic 6 surgery 6 surgery 7 department 7 department 8 for 8 for 9 help the palate defect was about 1 × [1] cm . 0 ###LEFT-WALL### 3 defect 0 ###LEFT-WALL### 4 was 0 ###LEFT-WALL### 10 . 1 the 3 defect 2 palate 3 defect 3 defect 4 was 4 was 5 about 5 about 9 cm 6 1 9 cm 7 × 9 cm we successfully reconstructed the oronasal fistula by using the angular artery cutaneous flap . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 reconstructed 0 ###LEFT-WALL### 14 . 1 we 3 reconstructed 2 successfully 3 reconstructed 3 reconstructed 6 fistula 3 reconstructed 7 by 4 the 6 fistula 5 oronasal 6 fistula 7 by 8 using 8 using 13 flap 9 the 13 flap 10 angular 11 artery 11 artery 13 flap 12 cutaneous 13 flap the flap successfully sealed the oral cavity during the [follow] [-] up period . 0 ###LEFT-WALL### 2 flap 0 ###LEFT-WALL### 4 sealed 0 ###LEFT-WALL### 14 . 1 the 2 flap 2 flap 4 sealed 3 successfully 4 sealed 4 sealed 7 cavity 4 sealed 8 during 5 the 7 cavity 6 oral 7 cavity 8 during 13 period 9 the 13 period 12 up 13 period conclusion : angular [artery] [cutaneous] [flap] is a good alternative for reconstruction of the oronasal fistula . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 17 . 2 : 3 angular 2 : 7 is 3 angular 7 is 7 is 10 alternative 8 a 9 good 8 a 10 alternative 9 good 10 alternative 10 alternative 11 for 11 for 12 reconstruction 12 reconstruction 13 of 13 of 16 fistula 14 the 16 fistula 15 oronasal 16 fistula especially in elderly patients , donor [-] site comorbidities are fewer due to the redundant aging skin and the missing tooth . 0 ###LEFT-WALL### 9 comorbidities 0 ###LEFT-WALL### 10 are 0 ###LEFT-WALL### 22 . 1 especially 9 comorbidities 2 in 4 patients 2 in 5 , 2 in 9 comorbidities 3 elderly 4 patients 6 donor 9 comorbidities 8 site 9 comorbidities 9 comorbidities 10 are 10 are 11 fewer 10 are 13 to 12 due 13 to 13 to 18 and 14 the 17 skin 15 redundant 17 skin 16 aging 17 skin 17 skin 18 and 18 and 21 tooth 19 the 21 tooth 20 missing 21 tooth objectives : the goal of the study was to improve prediction of longitudinal flight simulator performance by studying cognitive factors that may moderate the influence of chronological age . 0 ###LEFT-WALL### 1 objectives 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 29 . 2 : 4 goal 2 : 8 was 3 the 4 goal 4 goal 5 of 4 goal 8 was 5 of 7 study 6 the 7 study 8 was 9 to 9 to 10 improve 10 improve 11 prediction 10 improve 17 by 11 prediction 12 of 12 of 16 performance 13 longitudinal 14 flight 14 flight 16 performance 15 simulator 16 performance 17 by 18 studying 18 studying 20 factors 19 cognitive 20 factors 20 factors 21 that 20 factors 22 may 21 that 22 may 22 may 23 moderate 23 moderate 25 influence 24 the 25 influence 25 influence 26 of 26 of 28 age 27 chronological 28 age method : we examined age - related change in aviation performance in aircraft pilots in relation to baseline cognitive ability measures and aviation expertise . 0 ###LEFT-WALL### 1 method 0 ###LEFT-WALL### 2 : 2 : 3 we 2 : 4 examined 2 : 7 related 2 : 25 . 3 we 4 examined 4 examined 5 age 6 - 7 related 7 related 22 and 8 change 9 in 8 change 12 in 8 change 17 to 8 change 22 and 9 in 11 performance 10 aviation 11 performance 12 in 14 pilots 13 aircraft 14 pilots 15 in 16 relation 16 relation 17 to 17 to 21 measures 18 baseline 21 measures 19 cognitive 20 ability 20 ability 21 measures 22 and 24 expertise 23 aviation 24 expertise participants were aircraft pilots ( n = 276 ) aged 40 - 77.9 . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 2 were 0 ###LEFT-WALL### 14 . 1 participants 2 were 2 were 4 pilots 2 were 10 aged 3 aircraft 4 pilots 4 pilots 7 = 5 ( 7 = 6 n 7 = 7 = 8 276 7 = 9 ) 10 aged 12 - 11 40 12 - 12 - 13 77.9 flight simulator performance and cognition were tested yearly [;] there were an average of 4.3 ( ± 2.7 ; range 1 - 13 [ )(data points per participant . 0 ###LEFT-WALL### 1 flight 0 ###LEFT-WALL### 11 were 0 ###LEFT-WALL### 19 ; 1 flight 4 and 1 flight 6 were 1 flight 7 tested 1 flight 8 yearly 1 flight 11 were 2 simulator 3 performance 3 performance 4 and 4 and 5 cognition 4 and 6 were 8 yearly 10 there 11 were 13 average 12 an 13 average 13 average 14 of 13 average 17 ± 14 of 15 4.3 16 ( 17 ± 17 ± 18 2.7 17 ± 19 ; 19 ; 20 range 20 range 21 1 21 1 26 points 22 - 26 points 23 13 26 points 25 )(data 26 points 26 points 27 per 26 points 29 . 27 per 28 participant each participant was classified into one of the three levels of aviation expertise based on federal aviation administration pilot proficiency ratings : least , moderate , or high expertise . 0 ###LEFT-WALL### 2 participant 0 ###LEFT-WALL### 3 was 0 ###LEFT-WALL### 24 , 0 ###LEFT-WALL### 30 . 1 each 2 participant 2 participant 3 was 3 was 4 classified 4 classified 5 into 5 into 6 one 6 one 7 of 6 one 11 of 7 of 10 levels 8 the 9 three 9 three 10 levels 11 of 12 aviation 12 aviation 13 expertise 12 aviation 22 : 13 expertise 14 based 13 expertise 22 : 14 based 15 on 15 on 21 ratings 16 federal 17 aviation 17 aviation 18 administration 18 administration 20 proficiency 19 pilot 20 proficiency 20 proficiency 21 ratings 22 : 23 least 24 , 29 expertise 25 moderate 27 or 26 , 27 or 27 or 28 high 27 or 29 expertise results : addition of measures of cognitive processing speed and executive function to a model of age - related change in aviation performance significantly improved the model . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 28 . 2 : 3 addition 2 : 25 improved 3 addition 4 of 3 addition 6 of 3 addition 25 improved 4 of 5 measures 6 of 10 and 7 cognitive 9 speed 8 processing 9 speed 9 speed 10 and 10 and 12 function 10 and 13 to 10 and 16 of 11 executive 12 function 13 to 15 model 14 a 15 model 16 of 17 age 18 - 19 related 19 related 20 change 19 related 21 in 19 related 25 improved 21 in 23 performance 22 aviation 23 performance 24 significantly 25 improved 25 improved 27 model 26 the 27 model processing speed and executive function performance interacted such that the slowest rate of decline [in] flight simulator performance was found in aviators with the highest scores on tests of these abilities . 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 7 interacted 0 ###LEFT-WALL### 32 . 1 processing 2 speed 2 speed 3 and 3 and 6 performance 3 and 7 interacted 4 executive 5 function 5 function 6 performance 7 interacted 9 that 7 interacted 21 in 8 such 9 that 9 that 12 rate 9 that 20 found 10 the 11 slowest 10 the 12 rate 12 rate 13 of 12 rate 19 was 13 of 18 performance 14 decline 18 performance 16 flight 18 performance 17 simulator 18 performance 19 was 20 found 21 in 22 aviators 22 aviators 23 with 23 with 26 scores 24 the 25 highest 24 the 26 scores 26 scores 27 on 26 scores 29 of 27 on 28 tests 29 of 31 abilities 30 these 31 abilities expertise was beneficial to pilots across the age range studied ; however , expertise did not show evidence of reducing the effect of age . 0 ###LEFT-WALL### 1 expertise 0 ###LEFT-WALL### 2 was 0 ###LEFT-WALL### 11 ; 0 ###LEFT-WALL### 25 . 1 expertise 2 was 2 was 3 beneficial 3 beneficial 4 to 3 beneficial 6 across 4 to 5 pilots 6 across 9 range 7 the 9 range 8 age 9 range 9 range 10 studied 11 ; 14 expertise 11 ; 17 show 12 however 13 , 12 however 14 expertise 14 expertise 15 did 15 did 16 not 15 did 17 show 17 show 18 evidence 18 evidence 19 of 19 of 20 reducing 20 reducing 22 effect 21 the 22 effect 22 effect 23 of 23 of 24 age discussion : these data suggest that longitudinal performance on an important real - world activity can be predicted by initial assessment of relevant cognitive abilities . 0 ###LEFT-WALL### 1 discussion 0 ###LEFT-WALL### 2 : 2 : 4 data 2 : 5 suggest 2 : 18 predicted 3 these 4 data 4 data 5 suggest 5 suggest 6 that 6 that 8 performance 6 that 18 predicted 7 longitudinal 8 performance 8 performance 9 on 8 performance 15 activity 8 performance 17 be 8 performance 18 predicted 9 on 14 world 10 an 11 important 10 an 14 world 11 important 14 world 12 real 13 - 12 real 14 world 15 activity 16 can 16 can 17 be 18 predicted 19 by 18 predicted 26 . 19 by 21 assessment 20 initial 21 assessment 21 assessment 22 of 22 of 25 abilities 23 relevant 25 abilities 24 cognitive 25 abilities background : neopterin is a monocyte/macrophage - derived immune activation marker and its levels increase with age . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 3 neopterin 2 : 4 is 2 : 12 and 2 : 18 . 3 neopterin 4 is 4 is 11 marker 5 a 6 monocyte/macrophage 5 a 11 marker 6 monocyte/macrophage 7 - 6 monocyte/macrophage 10 activation 8 derived 10 activation 9 immune 10 activation 10 activation 11 marker 12 and 14 levels 12 and 15 increase 13 its 14 levels 14 levels 15 increase 15 increase 16 with 16 with 17 age frailty is an important clinical syndrome of old age . 0 ###LEFT-WALL### 1 frailty 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 10 . 1 frailty 2 is 2 is 6 syndrome 3 an 4 important 3 an 6 syndrome 4 important 6 syndrome 5 clinical 6 syndrome 6 syndrome 7 of 7 of 9 age 8 old 9 age previous studies have shown significant association [between] elevated interleukin - 6 ( il - 6 ) levels and frailty . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 4 shown 0 ###LEFT-WALL### 20 . 1 previous 2 studies 2 studies 3 have 3 have 4 shown 4 shown 9 interleukin 4 shown 17 levels 4 shown 18 and 5 significant 6 association 6 association 8 elevated 8 elevated 9 interleukin 9 interleukin 11 6 10 - 11 6 11 6 13 il 11 6 16 ) 12 ( 13 il 13 il 15 6 13 il 16 ) 14 - 15 6 15 6 16 ) 18 and 19 frailty the objective of this study was to evaluate il - 6 - independent association [of] serum neopterin levels with prevalent frailty . 0 ###LEFT-WALL### 2 objective 0 ###LEFT-WALL### 10 - 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 evaluate 7 to 8 evaluate 8 evaluate 9 il 10 - 11 6 10 - 12 - 10 - 22 . 11 6 12 - 12 - 17 neopterin 13 independent 14 association 14 association 17 neopterin 16 serum 17 neopterin 17 neopterin 18 levels 18 levels 19 with 19 with 21 frailty 20 prevalent 21 frailty methods : this is a cross - sectional study in community [-] dwelling older adults recruited from residential and retirement communities in baltimore , md , usa . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 3 this 2 : 4 is 3 this 4 is 4 is 6 cross 5 a 6 cross 6 cross 9 study 7 - 9 study 8 sectional 9 study 9 study 10 in 9 study 16 recruited 9 study 17 from 9 study 22 in 9 study 25 md 9 study 28 . 10 in 15 adults 11 community 13 dwelling 13 dwelling 15 adults 14 older 15 adults 17 from 19 and 18 residential 19 and 19 and 21 communities 20 retirement 21 communities 22 in 23 baltimore 24 , 25 md 25 md 27 usa 25 md 28 . 26 , 27 usa 27 usa 28 . frailty was determined using validated screening criteria . 0 ###LEFT-WALL### 1 frailty 0 ###LEFT-WALL### 2 was 0 ###LEFT-WALL### 8 . 1 frailty 2 was 2 was 3 determined 3 determined 4 using 4 using 7 criteria 5 validated 7 criteria 6 screening 7 criteria serum neopterin and il - 6 levels were measured using standard enzyme - linked immunosorbent assay . 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 5 - 1 serum 2 neopterin 2 neopterin 3 and 3 and 4 il 5 - 7 levels 5 - 9 measured 5 - 13 - 6 6 7 levels 7 levels 8 were 8 were 9 measured 9 measured 10 using 10 using 12 enzyme 11 standard 12 enzyme 13 - 16 assay 13 - 17 . 14 linked 16 assay 15 immunosorbent 16 assay pearson correlation and multivariate linear regression analysis was performed to assess the relationship [between] log ( neopterin ) and log ( il - 6 ) . 0 ###LEFT-WALL### 2 correlation 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 26 . 1 pearson 2 correlation 3 and 7 analysis 3 and 9 performed 4 multivariate 7 analysis 5 linear 6 regression 6 regression 7 analysis 7 analysis 8 was 8 was 9 performed 9 performed 10 to 10 to 19 and 11 assess 15 log 11 assess 19 and 12 the 15 log 13 relationship 15 log 15 log 17 neopterin 16 ( 17 neopterin 17 neopterin 18 ) 19 and 20 log 20 log 23 - 21 ( 23 - 22 il 23 - 23 - 24 6 23 - 25 ) results : one hundred and thirty - three individuals with a mean age of 84 years ( range 72 - 97 ) completed the study . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 7 - 1 results 2 : 2 : 6 thirty 3 one 4 hundred 4 hundred 5 and 5 and 6 thirty 7 - 9 individuals 7 - 23 completed 7 - 26 . 8 three 9 individuals 9 individuals 10 with 9 individuals 14 of 9 individuals 18 range 9 individuals 23 completed 10 with 13 age 11 a 12 mean 11 a 13 age 12 mean 13 age 14 of 16 years 15 84 16 years 17 ( 18 range 18 range 20 - 18 range 22 ) 19 72 20 - 20 - 21 97 23 completed 25 study 24 the 25 study neopterin levels were significantly higher in frail older adults than those in [non] [-] frail controls [ median [:] 8.94 versus 8.35 nm , respectively , p < 0.001 [t] - [test] on log [(] neopterin [ )(] . 0 ###LEFT-WALL### 2 levels 0 ###LEFT-WALL### 3 were 0 ###LEFT-WALL### 39 . 1 neopterin 2 levels 2 levels 3 were 3 were 4 significantly 3 were 5 higher 5 higher 6 in 5 higher 10 than 5 higher 25 respectively 5 higher 28 < 5 higher 33 on 6 in 9 adults 7 frail 9 adults 8 older 9 adults 10 than 11 those 10 than 12 in 12 in 16 controls 15 frail 16 controls 16 controls 18 median 17 [ 18 median 18 median 20 8.94 18 median 21 versus 18 median 24 , 21 versus 23 nm 22 8.35 23 nm 24 , 25 respectively 25 respectively 26 , 27 p 28 < 28 < 29 0.001 28 < 31 - 31 - 33 on 33 on 36 neopterin 33 on 38 )(] 34 log 36 neopterin log ( neopterin ) was significantly associated with prevalent frailty , adjusting for log [(] il - 6 ) . 0 ###LEFT-WALL### 1 log 0 ###LEFT-WALL### 7 associated 0 ###LEFT-WALL### 20 . 1 log 3 neopterin 1 log 5 was 2 ( 3 neopterin 3 neopterin 4 ) 5 was 7 associated 6 significantly 7 associated 7 associated 8 with 8 with 10 frailty 9 prevalent 10 frailty 10 frailty 12 adjusting 11 , 12 adjusting 12 adjusting 13 for 12 adjusting 19 ) 13 for 16 il 14 log 16 il 16 il 18 6 17 - 18 6 18 6 19 ) participants in the top tertile of neopterin had or of 3.80 [ 95 % confidence [interval] ( ci ) = 1.36 - 10.6 , p < 0.01 ] for frailty . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 8 had 0 ###LEFT-WALL### 31 . 1 participants 2 in 1 participants 8 had 2 in 5 tertile 3 the 4 top 3 the 5 tertile 5 tertile 6 of 6 of 7 neopterin 8 had 9 or 8 had 22 - 8 had 26 < 8 had 29 for 9 or 10 of 9 or 15 confidence 10 of 11 3.80 12 [ 15 confidence 13 95 14 % 14 % 15 confidence 15 confidence 18 ci 15 confidence 19 ) 17 ( 18 ci 18 ci 19 ) 20 = 21 1.36 21 1.36 22 - 22 - 23 10.6 24 , 26 < 25 p 26 < 26 < 27 0.01 26 < 28 ] 29 for 30 frailty as expected , participants in the top tertile of il [-] 6 had or of 3.29 ( 95 % ci = 1.21 - 7.86 , p < 0.05 ) for frailty . 0 ###LEFT-WALL### 4 participants 0 ###LEFT-WALL### 13 had 1 as 2 expected 1 as 3 , 1 as 4 participants 2 expected 3 , 4 participants 5 in 4 participants 9 of 4 participants 13 had 5 in 8 tertile 6 the 8 tertile 7 top 8 tertile 9 of 10 il 10 il 12 6 13 had 14 or 14 or 15 of 14 or 19 % 15 of 16 3.29 17 ( 19 % 18 95 19 % 19 % 20 ci 19 % 21 = 19 % 32 . 20 ci 21 = 21 = 27 < 21 = 30 for 22 1.21 23 - 23 - 24 7.86 23 - 27 < 25 , 27 < 26 p 27 < 27 < 28 0.05 27 < 29 ) 30 for 31 frailty log ( neopterin ) correlated with log [(] il - 6 ) ( correlation coefficient [=] 0.19 , p < 0.05 ) . 0 ###LEFT-WALL### 1 log 0 ###LEFT-WALL### 5 correlated 0 ###LEFT-WALL### 23 . 1 log 3 neopterin 1 log 5 correlated 2 ( 3 neopterin 3 neopterin 4 ) 5 correlated 6 with 6 with 9 il 7 log 9 il 9 il 11 6 9 il 15 coefficient 9 il 20 < 10 - 11 6 11 6 12 ) 13 ( 15 coefficient 14 correlation 15 coefficient 15 coefficient 17 0.19 15 coefficient 18 , 18 , 20 < 19 p 20 < 20 < 21 0.05 20 < 22 ) moreover , or for participants in the top neopterin tertile remained significant after adjusting for il - 6 ( or = 3.97 , 95 % ci = 1.15 - 13.72 , p < 0.05 ) . 0 ###LEFT-WALL### 3 or 0 ###LEFT-WALL### 21 = 0 ###LEFT-WALL### 36 . 1 moreover 2 , 1 moreover 3 or 3 or 4 for 3 or 6 in 3 or 11 remained 4 for 5 participants 6 in 10 tertile 7 the 10 tertile 8 top 9 neopterin 9 neopterin 10 tertile 11 remained 12 significant 12 significant 13 after 13 after 14 adjusting 14 adjusting 15 for 15 for 20 or 16 il 17 - 16 il 20 or 18 6 20 or 19 ( 20 or 20 or 21 = 21 = 22 3.97 22 3.97 25 % 22 3.97 33 < 23 , 25 % 24 95 25 % 25 % 26 ci 25 % 27 = 25 % 31 , 26 ci 27 = 27 = 29 - 28 1.15 29 - 29 - 30 13.72 31 , 33 < 32 p 33 < 33 < 34 0.05 33 < 35 ) conclusion : elevated neopterin levels had il - 6 - independent association [with] prevalent frailty , suggesting potential monocyte/macrophage - mediated immune activation in the [frail] elderly . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 5 levels 2 : 6 had 2 : 8 - 2 : 10 - 3 elevated 4 neopterin 4 neopterin 5 levels 5 levels 6 had 6 had 7 il 8 - 9 6 10 - 15 frailty 10 - 21 mediated 10 - 28 . 11 independent 12 association 12 association 15 frailty 14 prevalent 15 frailty 15 frailty 17 suggesting 15 frailty 21 mediated 16 , 17 suggesting 17 suggesting 18 potential 17 suggesting 19 monocyte/macrophage 17 suggesting 20 - 21 mediated 23 activation 21 mediated 24 in 22 immune 23 activation 24 in 27 elderly 25 the 27 elderly chronological age is used as a marker for age - associated changes [in] cognitive function . 0 ###LEFT-WALL### 2 age 0 ###LEFT-WALL### 4 used 0 ###LEFT-WALL### 10 - 1 chronological 2 age 2 age 3 is 3 is 4 used 4 used 5 as 5 as 7 marker 6 a 7 marker 7 marker 8 for 8 for 9 age 10 - 15 function 10 - 16 . 11 associated 12 changes 12 changes 15 function 14 cognitive 15 function however , there is great interindividual variability in cognitive ability among people of the same age . 0 ###LEFT-WALL### 3 there 0 ###LEFT-WALL### 4 is 0 ###LEFT-WALL### 17 . 1 however 2 , 1 however 3 there 3 there 4 is 4 is 7 variability 5 great 7 variability 6 interindividual 7 variability 7 variability 8 in 8 in 10 ability 9 cognitive 10 ability 10 ability 11 among 11 among 12 people 12 people 13 of 13 of 16 age 14 the 15 same 15 same 16 age physiological age rather [than] chronological age should be more closely associated with age - related cognitive changes because these changes are not universal and [are] likely dependent on several factors in addition to the number of years lived . 0 ###LEFT-WALL### 6 age 0 ###LEFT-WALL### 15 related 0 ###LEFT-WALL### 22 not 0 ###LEFT-WALL### 39 . 1 physiological 6 age 2 age 6 age 3 rather 5 chronological 5 chronological 6 age 6 age 7 should 7 should 8 be 8 be 11 associated 9 more 10 closely 10 closely 11 associated 11 associated 12 with 12 with 13 age 14 - 15 related 15 related 17 changes 15 related 18 because 16 cognitive 17 changes 18 because 20 changes 18 because 21 are 19 these 20 changes 20 changes 21 are 22 not 24 and 22 not 38 lived 23 universal 24 and 24 and 27 dependent 24 and 28 on 24 and 33 to 24 and 36 of 24 and 38 lived 26 likely 27 dependent 28 on 30 factors 29 several 30 factors 30 factors 31 in 31 in 32 addition 33 to 35 number 34 the 35 number 36 of 37 years cognitive [function] is associated with successful [self] - management , and a biological marker that reflects physiological age and [is] associated [with] cognitive function could be used to identify risk for failure to [self] [-] manage . 0 ###LEFT-WALL### 1 cognitive 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 37 . 1 cognitive 3 is 3 is 4 associated 4 associated 5 with 5 with 9 management 6 successful 8 - 6 successful 9 management 10 , 11 and 11 and 14 marker 11 and 27 used 12 a 14 marker 13 biological 14 marker 14 marker 15 that 14 marker 16 reflects 14 marker 25 could 15 that 16 reflects 16 reflects 19 and 17 physiological 18 age 18 age 19 and 19 and 24 function 21 associated 24 function 23 cognitive 24 function 25 could 26 be 26 be 27 used 27 used 28 to 27 used 29 identify 28 to 29 identify 29 identify 30 risk 29 identify 31 for 31 for 32 failure 32 failure 33 to 32 failure 36 manage 33 to 36 manage the purpose of this study was to investigate the association between telomere length , a known biomarker of age ; blood pressure ; cognitive assessments [;] and adherence to antihypertensive medication [among] community - dwelling middle - aged and older adults . 0 ###LEFT-WALL### 2 purpose 0 ###LEFT-WALL### 20 ; 0 ###LEFT-WALL### 42 . 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 investigate 7 to 8 investigate 8 investigate 10 association 8 investigate 11 between 9 the 10 association 11 between 13 length 12 telomere 13 length 13 length 17 biomarker 14 , 17 biomarker 15 a 17 biomarker 16 known 17 biomarker 17 biomarker 18 of 17 biomarker 20 ; 18 of 19 age 20 ; 21 blood 20 ; 23 ; 21 blood 22 pressure 23 ; 33 community 23 ; 34 - 24 cognitive 25 assessments 25 assessments 27 and 27 and 28 adherence 27 and 29 to 27 and 33 community 29 to 31 medication 30 antihypertensive 31 medication 34 - 36 middle 34 - 37 - 35 dwelling 36 middle 37 - 41 adults 38 aged 39 and 39 and 40 older 39 and 41 adults the authors administered a battery of cognitive assessments to 42 participants ( m = 69 years of age [ )(, collected blood samples , and isolated peripheral blood mononuclear leukocytes for genomic dna . 0 ###LEFT-WALL### 2 authors 0 ###LEFT-WALL### 20 )(, 0 ###LEFT-WALL### 34 . 1 the 2 authors 2 authors 20 )(, 3 administered 5 battery 3 administered 20 )(, 4 a 5 battery 5 battery 6 of 5 battery 17 of 6 of 8 assessments 7 cognitive 8 assessments 8 assessments 9 to 8 assessments 14 = 9 to 11 participants 10 42 11 participants 12 ( 14 = 13 m 14 = 14 = 16 years 15 69 16 years 17 of 18 age 20 )(, 25 and 21 collected 23 samples 21 collected 25 and 22 blood 23 samples 24 , 25 and 25 and 26 isolated 26 isolated 30 leukocytes 27 peripheral 28 blood 28 blood 30 leukocytes 29 mononuclear 30 leukocytes 30 leukocytes 31 for 31 for 33 dna 32 genomic 33 dna the authors determined relative telomere length using cawthon 's method for real - time quantitative polymerase chain reaction ( rt - qpcr ) and measured medication adherence using an electronic medication monitoring system ( mems by aardex ) over 8 weeks . 0 ###LEFT-WALL### 2 authors 0 ###LEFT-WALL### 3 determined 0 ###LEFT-WALL### 13 - 1 the 2 authors 2 authors 3 determined 3 determined 6 length 3 determined 7 using 4 relative 6 length 5 telomere 6 length 7 using 10 method 7 using 12 real 8 cawthon 9 's 9 's 10 method 11 for 12 real 13 - 14 time 13 - 42 . 14 time 18 reaction 14 time 39 over 15 quantitative 16 polymerase 16 polymerase 17 chain 17 chain 18 reaction 18 reaction 24 and 19 ( 24 and 20 rt 22 qpcr 20 rt 24 and 21 - 22 qpcr 22 qpcr 23 ) 24 and 27 adherence 24 and 28 using 24 and 35 mems 24 and 38 ) 25 measured 27 adherence 26 medication 27 adherence 28 using 33 system 29 an 30 electronic 29 an 33 system 30 electronic 31 medication 31 medication 33 system 32 monitoring 33 system 34 ( 35 mems 35 mems 36 by 35 mems 38 ) 36 by 37 aardex 39 over 41 weeks 40 8 41 weeks findings indicate that telomere length was inversely associated with systolic blood pressure ( r = - [.] 38 , p < [.] 01 ) [and] diastolic blood pressure ( r = - [.] 42 , p < [.] 01 ) but not with cognitive assessments or adherence . 0 ###LEFT-WALL### 1 findings 0 ###LEFT-WALL### 2 indicate 0 ###LEFT-WALL### 48 . 1 findings 2 indicate 2 indicate 3 that 3 that 5 length 3 that 8 associated 4 telomere 5 length 5 length 6 was 6 was 8 associated 7 inversely 8 associated 8 associated 9 with 8 associated 41 but 8 associated 43 with 9 with 12 pressure 9 with 28 pressure 10 systolic 11 blood 11 blood 12 pressure 12 pressure 16 - 13 ( 16 - 14 r 15 = 15 = 16 - 16 - 18 38 16 - 24 ) 18 38 21 < 19 , 21 < 20 p 21 < 21 < 23 01 26 diastolic 27 blood 27 blood 28 pressure 28 pressure 32 - 29 ( 32 - 30 r 31 = 31 = 32 - 32 - 34 42 32 - 40 ) 34 42 37 < 35 , 37 < 36 p 37 < 37 < 39 01 41 but 42 not 43 with 46 or 44 cognitive 45 assessments 45 assessments 46 or 46 or 47 adherence the authors discuss the nonsignificant findings between telomere length and cognitive assessments including the potential modifying role of gender . 0 ###LEFT-WALL### 2 authors 0 ###LEFT-WALL### 3 discuss 0 ###LEFT-WALL### 20 . 1 the 2 authors 2 authors 3 discuss 3 discuss 6 findings 3 discuss 7 between 4 the 6 findings 5 nonsignificant 6 findings 7 between 10 and 8 telomere 9 length 9 length 10 and 10 and 12 assessments 10 and 13 including 11 cognitive 12 assessments 13 including 17 role 14 the 17 role 15 potential 17 role 16 modifying 17 role 17 role 18 of 18 of 19 gender the purpose of this study was to further examine potential biomarkers of cognitive aging by looking at the associations among oxidative stress , cognitive abilities , and medication adherence in a community - based sample of middle - aged and older adults ( n = 42 [;] mean age = 69 years [ )(prescribed at least one medication for hypertension . 0 ###LEFT-WALL### 2 purpose 0 ###LEFT-WALL### 9 examine 1 the 2 purpose 2 purpose 3 of 2 purpose 6 was 3 of 5 study 4 this 5 study 6 was 7 to 7 to 9 examine 8 further 9 examine 9 examine 11 biomarkers 9 examine 17 at 9 examine 20 among 10 potential 11 biomarkers 11 biomarkers 12 of 12 of 14 aging 13 cognitive 14 aging 14 aging 15 by 15 by 16 looking 17 at 19 associations 18 the 19 associations 20 among 22 stress 21 oxidative 22 stress 22 stress 33 - 23 , 33 - 24 cognitive 25 abilities 25 abilities 27 and 26 , 27 and 27 and 29 adherence 27 and 30 in 27 and 33 - 28 medication 29 adherence 30 in 32 community 31 a 32 community 33 - 35 sample 34 based 35 sample 35 sample 36 of 36 of 37 middle 37 middle 49 age 38 - 49 age 39 aged 40 and 40 and 42 adults 40 and 45 = 40 and 49 age 41 older 42 adults 43 ( 45 = 44 n 45 = 45 = 46 42 48 mean 49 age 49 age 52 years 49 age 54 )(prescribed 49 age 61 . 50 = 51 69 51 69 52 years 52 years 54 )(prescribed 54 )(prescribed 58 medication 55 at 56 least 56 least 57 one 57 one 58 medication 58 medication 59 for 59 for 60 hypertension in addition to measures described in part i , " biomarkers for cognitive aging , " a 12 [-] hr urine collection for f ( 2 ) - isoprostanes served as an indicator of oxidative stress . 0 ###LEFT-WALL### 11 biomarkers 0 ###LEFT-WALL### 30 served 0 ###LEFT-WALL### 37 . 1 in 2 addition 1 in 9 , 1 in 11 biomarkers 2 addition 3 to 2 addition 5 described 3 to 4 measures 5 described 6 in 6 in 7 part 7 part 8 i 9 , 10 " 11 biomarkers 12 for 11 biomarkers 30 served 12 for 13 cognitive 13 cognitive 14 aging 13 cognitive 29 isoprostanes 14 aging 22 collection 14 aging 29 isoprostanes 15 , 16 " 15 , 22 collection 17 a 22 collection 18 12 20 hr 20 hr 21 urine 21 urine 22 collection 22 collection 23 for 22 collection 26 2 22 collection 28 - 23 for 24 f 25 ( 26 2 26 2 27 ) 30 served 31 as 31 as 33 indicator 32 an 33 indicator 33 indicator 34 of 34 of 36 stress 35 oxidative 36 stress participants completed a battery of cognitive assessments and 8 weeks of electronic medication monitoring for adherence [to] one antihypertensive agent . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 2 completed 0 ###LEFT-WALL### 21 . 1 participants 2 completed 2 completed 4 battery 3 a 4 battery 4 battery 5 of 5 of 8 and 6 cognitive 7 assessments 7 assessments 8 and 8 and 10 weeks 8 and 11 of 9 8 10 weeks 11 of 13 medication 12 electronic 13 medication 13 medication 14 monitoring 14 monitoring 15 for 14 monitoring 20 agent 15 for 16 adherence 16 adherence 18 one 19 antihypertensive 20 agent oxidative stress was significantly associated with logical memory , immediate ( r = - [.] 38 , p < [.] 01 [ )( delayed recall ( r = - [.] 42 , p < [.] 01 [ )(, [and] recognition memory ( r = - [.] 42 , p < [.] 01 [ )(from the wechsler memory scale iii [,] number of perseveration errors ( r = [.] 26 , p < [.] 05 [ )( categories achieved ( r = - [.] 26 , p < [.] 01 [ )(on the wisconsin card sorting test ( wsct ) , and medication adherence ( r = - [.] 34 , p < [.] 05 [ )( 1 oxidative 2 stress 2 stress 3 was 3 was 5 associated 4 significantly 5 associated 5 associated 6 with 5 associated 9 , 5 associated 10 immediate 6 with 8 memory 7 logical 8 memory 10 immediate 13 = 11 ( 13 = 12 r 13 = 13 = 16 38 14 - 16 38 16 38 19 < 17 , 19 < 18 p 19 < 19 < 25 recall 21 01 24 delayed 24 delayed 25 recall 25 recall 29 - 25 recall 34 < 26 ( 29 - 27 r 28 = 28 = 29 - 29 - 31 42 32 , 34 < 33 p 34 < 34 < 36 01 36 01 45 - 38 )(, 45 - 40 recognition 41 memory 41 memory 44 = 42 ( 44 = 43 r 44 = 44 = 45 - 45 - 47 42 47 42 50 < 48 , 50 < 49 p 50 < 50 < 52 01 52 01 54 )(from 52 01 62 of 54 )(from 61 number 55 the 61 number 56 wechsler 57 memory 57 memory 61 number 58 scale 59 iii 58 scale 61 number 62 of 64 errors 63 perseveration 64 errors 64 errors 67 = 64 errors 72 < 65 ( 67 = 66 r 67 = 67 = 69 26 67 = 70 , 71 p 72 < 72 < 77 categories 74 05 77 categories 77 categories 78 achieved 77 categories 82 - 79 ( 82 - 80 r 81 = 81 = 82 - 82 - 84 26 84 26 87 < 85 , 87 < 86 p 87 < 87 < 89 01 89 01 91 )(on 91 )(on 103 adherence 92 the 103 adherence 93 wisconsin 94 card 94 card 95 sorting 95 sorting 96 test 96 test 98 wsct 97 ( 98 wsct 98 wsct 99 ) 98 wsct 101 and 100 , 101 and 101 and 102 medication 101 and 103 adherence 103 adherence 107 - 104 ( 107 - 105 r 106 = 106 = 107 - 107 - 109 34 107 - 116 )( 109 34 112 < 110 , 112 < 111 p 112 < 112 < 114 05 findings indicate that a biomarker of oxidative stress [,] f ( 2 ) - isoprostanes corrected for vitamin e , is significantly associated with cognitive measures and a functional outcome . 0 ###LEFT-WALL### 1 findings 0 ###LEFT-WALL### 2 indicate 0 ###LEFT-WALL### 31 . 1 findings 2 indicate 2 indicate 3 that 3 that 5 biomarker 3 that 23 associated 4 a 5 biomarker 5 biomarker 6 of 5 biomarker 21 is 6 of 8 stress 7 oxidative 8 stress 8 stress 10 f 8 stress 12 2 8 stress 15 isoprostanes 11 ( 12 2 12 2 13 ) 14 - 15 isoprostanes 15 isoprostanes 16 corrected 15 isoprostanes 20 , 16 corrected 17 for 17 for 18 vitamin 18 vitamin 19 e 21 is 22 significantly 21 is 23 associated 23 associated 24 with 24 with 27 and 25 cognitive 26 measures 26 measures 27 and 27 and 30 outcome 28 a 29 functional 28 a 30 outcome 29 functional 30 outcome none the provision of nutrition has traditionally been driven by the desire to provide adequate calories . 0 ###LEFT-WALL### 1 none 0 ###LEFT-WALL### 14 provide 0 ###LEFT-WALL### 17 . 1 none 3 provision 1 none 13 to 1 none 14 provide 2 the 3 provision 3 provision 4 of 3 provision 6 has 4 of 5 nutrition 6 has 8 been 7 traditionally 8 been 8 been 9 driven 9 driven 10 by 9 driven 13 to 10 by 12 desire 11 the 12 desire 14 provide 16 calories 15 adequate 16 calories however , over the past decade it has become evident that provision of excess calories can be detrimental to patients ' outcomes in both critical care and long - term care settings . 0 ###LEFT-WALL### 7 it 0 ###LEFT-WALL### 9 become 0 ###LEFT-WALL### 33 . 1 however 2 , 1 however 7 it 3 over 6 decade 3 over 7 it 4 the 5 past 4 the 6 decade 7 it 8 has 8 has 9 become 9 become 10 evident 10 evident 11 that 11 that 12 provision 11 that 17 be 12 provision 13 of 12 provision 16 can 13 of 15 calories 14 excess 15 calories 16 can 17 be 17 be 18 detrimental 18 detrimental 19 to 18 detrimental 23 in 19 to 22 outcomes 20 patients 21 ' 21 ' 22 outcomes 23 in 27 and 24 both 25 critical 25 critical 26 care 26 care 27 and 27 and 32 settings 28 long 29 - 28 long 30 term 30 term 31 care 31 care 32 settings this review examines patient populations for whom hypocaloric nutrition can be both appropriate and beneficial . 0 ###LEFT-WALL### 2 review 0 ###LEFT-WALL### 3 examines 0 ###LEFT-WALL### 16 . 1 this 2 review 2 review 3 examines 3 examines 5 populations 3 examines 14 and 4 patient 5 populations 5 populations 6 for 6 for 7 whom 6 for 9 nutrition 6 for 11 be 8 hypocaloric 9 nutrition 9 nutrition 10 can 10 can 11 be 11 be 12 both 13 appropriate 14 and 14 and 15 beneficial in specific situations , critically ill patients , such as those with obesity , stroke , and spinal cord injury , may have decreased energy requirements . 0 ###LEFT-WALL### 7 patients 0 ###LEFT-WALL### 24 decreased 0 ###LEFT-WALL### 27 . 1 in 3 situations 1 in 4 , 1 in 7 patients 2 specific 3 situations 5 critically 6 ill 6 ill 7 patients 7 patients 10 as 7 patients 22 may 8 , 10 as 9 such 10 as 10 as 17 and 10 as 21 , 11 those 12 with 11 those 14 , 12 with 13 obesity 14 , 15 stroke 14 , 17 and 16 , 17 and 17 and 20 injury 18 spinal 19 cord 19 cord 20 injury 22 may 23 have 23 have 24 decreased 24 decreased 26 requirements 25 energy 26 requirements in patients with spinal cord injury , the level of injury significantly correlates with the extent of reduced caloric energy expenditure . 0 ###LEFT-WALL### 9 level 0 ###LEFT-WALL### 13 correlates 0 ###LEFT-WALL### 22 . 1 in 2 patients 1 in 7 , 1 in 9 level 2 patients 3 with 3 with 6 injury 4 spinal 5 cord 5 cord 6 injury 8 the 9 level 9 level 10 of 9 level 13 correlates 10 of 11 injury 12 significantly 13 correlates 13 correlates 14 with 14 with 16 extent 15 the 16 extent 16 extent 17 of 17 of 21 expenditure 18 reduced 20 energy 19 caloric 20 energy 20 energy 21 expenditure ventilator - dependent patients with amyotrophic lateral sclerosis ( als ) have decreased energy needs ; energy expenditure for als patients is lower than the predictive equation value . 0 ###LEFT-WALL### 4 patients 0 ###LEFT-WALL### 13 decreased 0 ###LEFT-WALL### 16 ; 0 ###LEFT-WALL### 29 . 1 ventilator 2 - 1 ventilator 4 patients 3 dependent 4 patients 4 patients 5 with 4 patients 10 als 4 patients 12 have 5 with 8 sclerosis 6 amyotrophic 8 sclerosis 7 lateral 8 sclerosis 9 ( 10 als 10 als 11 ) 12 have 13 decreased 13 decreased 15 needs 14 energy 15 needs 16 ; 18 expenditure 16 ; 22 is 17 energy 18 expenditure 18 expenditure 19 for 18 expenditure 22 is 19 for 21 patients 20 als 21 patients 22 is 23 lower 23 lower 24 than 24 than 28 value 25 the 28 value 26 predictive 27 equation 27 equation 28 value aging patients will have decreased energy needs relative to a reduction in lean [body] mass . 0 ###LEFT-WALL### 1 aging 0 ###LEFT-WALL### 4 have 0 ###LEFT-WALL### 16 . 1 aging 2 patients 1 aging 3 will 3 will 4 have 4 have 7 needs 4 have 15 mass 5 decreased 6 energy 6 energy 7 needs 7 needs 8 relative 8 relative 9 to 8 relative 12 in 9 to 11 reduction 10 a 11 reduction 12 in 13 lean patients with cerebral palsy ( cp ) have significantly lower caloric requirements than anticipated using predictive equations . 0 ###LEFT-WALL### 1 patients 0 ###LEFT-WALL### 8 have 0 ###LEFT-WALL### 18 . 1 patients 2 with 1 patients 8 have 2 with 4 palsy 3 cerebral 4 palsy 4 palsy 6 cp 5 ( 6 cp 6 cp 7 ) 8 have 12 requirements 8 have 14 anticipated 8 have 15 using 9 significantly 10 lower 10 lower 12 requirements 11 caloric 12 requirements 13 than 14 anticipated 15 using 17 equations 16 predictive 17 equations patients with cp pose a particular challenge in nutrition assessment . 0 ###LEFT-WALL### 1 patients 0 ###LEFT-WALL### 4 pose 0 ###LEFT-WALL### 11 . 1 patients 2 with 1 patients 4 pose 2 with 3 cp 4 pose 7 challenge 4 pose 8 in 5 a 6 particular 5 a 7 challenge 6 particular 7 challenge 8 in 10 assessment 9 nutrition 10 assessment several studies demonstrate that patients with cp have significantly lower caloric requirements than anticipated using predictive equations ; thus , patients with cp benefit from indirect calorimetry . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 3 demonstrate 0 ###LEFT-WALL### 18 ; 0 ###LEFT-WALL### 28 . 1 several 2 studies 2 studies 3 demonstrate 3 demonstrate 4 that 4 that 5 patients 4 that 8 have 5 patients 6 with 5 patients 8 have 6 with 7 cp 8 have 12 requirements 8 have 15 using 9 significantly 10 lower 10 lower 12 requirements 11 caloric 12 requirements 12 requirements 14 anticipated 13 than 14 anticipated 15 using 17 equations 16 predictive 17 equations 18 ; 21 patients 18 ; 24 benefit 19 thus 20 , 19 thus 21 patients 21 patients 22 with 21 patients 24 benefit 22 with 23 cp 24 benefit 25 from 25 from 27 calorimetry 26 indirect 27 calorimetry provision of nutrition for obese patients is briefly addressed , as this is an increasingly important consideration for nutrition support in both the critical care and long - term care settings . 0 ###LEFT-WALL### 1 provision 0 ###LEFT-WALL### 9 addressed 0 ###LEFT-WALL### 10 , 0 ###LEFT-WALL### 32 . 1 provision 2 of 1 provision 7 is 2 of 3 nutrition 3 nutrition 4 for 4 for 6 patients 5 obese 6 patients 7 is 8 briefly 7 is 9 addressed 10 , 29 term 11 as 12 this 11 as 13 is 11 as 28 - 11 as 29 term 12 this 13 is 13 is 17 consideration 13 is 21 in 14 an 17 consideration 15 increasingly 16 important 16 important 17 consideration 17 consideration 18 for 18 for 20 support 19 nutrition 20 support 21 in 26 and 22 both 26 and 23 the 25 care 24 critical 25 care 25 care 26 and 26 and 27 long 29 term 31 settings 30 care 31 settings when indirect calorimetry is not available , clinicians should remember that most patients will have low resting energy expenditure regardless of functional status and [require] frequent evaluation during institution [of] nutrition recommendations to guard against overfeeding and obesity . 0 ###LEFT-WALL### 16 low 0 ###LEFT-WALL### 39 . 1 when 3 calorimetry 1 when 4 is 1 when 16 low 2 indirect 3 calorimetry 3 calorimetry 4 is 4 is 5 not 4 is 12 most 5 not 6 available 6 available 7 , 6 available 8 clinicians 8 clinicians 9 should 9 should 10 remember 10 remember 11 that 12 most 13 patients 12 most 15 have 13 patients 14 will 14 will 15 have 16 low 19 expenditure 16 low 21 of 17 resting 19 expenditure 18 energy 19 expenditure 20 regardless 21 of 21 of 37 and 22 functional 23 status 23 status 24 and 24 and 27 evaluation 24 and 28 during 24 and 37 and 26 frequent 27 evaluation 28 during 32 recommendations 29 institution 32 recommendations 31 nutrition 32 recommendations 32 recommendations 33 to 32 recommendations 34 guard 33 to 34 guard 34 guard 35 against 35 against 36 overfeeding 37 and 38 obesity none [the] [role] of climate [in] driving selection of mtdna as homo sapiens migrated out of africa into eurasia remains controversial . 0 ###LEFT-WALL### 8 selection 0 ###LEFT-WALL### 20 remains 0 ###LEFT-WALL### 22 . 1 none 4 of 1 none 8 selection 4 of 8 selection 5 climate 7 driving 7 driving 8 selection 8 selection 9 of 8 selection 16 of 8 selection 20 remains 9 of 10 mtdna 10 mtdna 11 as 10 mtdna 13 sapiens 10 mtdna 15 out 11 as 12 homo 13 sapiens 14 migrated 14 migrated 15 out 16 of 17 africa 17 africa 18 into 18 into 19 eurasia 20 remains 21 controversial common african haplogroups l0 , l2 and l3 had significantly lower rmrs than european haplogroups h , jt and uk with haplogroup l1 rmr being intermediate to these groups . 0 ###LEFT-WALL### 7 and 0 ###LEFT-WALL### 9 had 0 ###LEFT-WALL### 30 . 1 common 2 african 2 african 3 haplogroups 3 haplogroups 4 l0 4 l0 5 , 5 , 6 l2 5 , 7 and 7 and 8 l3 7 and 9 had 9 had 12 rmrs 9 had 13 than 9 had 21 with 10 significantly 11 lower 11 lower 12 rmrs 13 than 19 and 14 european 15 haplogroups 15 haplogroups 16 h 15 haplogroups 17 , 17 , 18 jt 17 , 19 and 19 and 20 uk 21 with 24 rmr 22 haplogroup 24 rmr 23 l1 24 rmr 24 rmr 25 being 25 being 26 intermediate 26 intermediate 27 to 27 to 29 groups 28 these 29 groups this study links mitochondrial haplogroups with ancestry [-] associated differences in metabolic rate [and] energy expenditure . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 links 0 ###LEFT-WALL### 17 . 1 this 2 study 2 study 3 links 3 links 5 haplogroups 3 links 6 with 3 links 11 in 4 mitochondrial 5 haplogroups 6 with 10 differences 7 ancestry 9 associated 9 associated 10 differences 11 in 16 expenditure 12 metabolic 13 rate 13 rate 16 expenditure 15 energy 16 expenditure objective : to present an overview of the prevalence of multimorbidity and comorbidity of chronic diseases in the dutch population . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 2 : 3 to 2 : 4 present 2 : 21 . 3 to 4 present 4 present 6 overview 4 present 17 in 5 an 6 overview 6 overview 7 of 7 of 9 prevalence 8 the 9 prevalence 9 prevalence 10 of 9 prevalence 14 of 10 of 12 and 11 multimorbidity 12 and 12 and 13 comorbidity 14 of 16 diseases 15 chronic 16 diseases 17 in 20 population 18 the 20 population 19 dutch 20 population design : data analysis . 0 ###LEFT-WALL### 1 design 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 5 . 1 design 2 : 2 : 4 analysis 3 data 4 analysis methods : data from the netherlands information network of general practice ( linh ) , a large representative network of general practices over a period of 7 years ( 2002 - 2008 ) were analysed . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 3 data 2 : 34 were 2 : 36 . 3 data 4 from 3 data 19 network 3 data 34 were 4 from 8 network 5 the 8 network 6 netherlands 7 information 7 information 8 network 8 network 9 of 8 network 13 linh 9 of 11 practice 10 general 11 practice 12 ( 13 linh 13 linh 14 ) 15 , 19 network 16 a 19 network 17 large 19 network 18 representative 19 network 19 network 20 of 19 network 26 of 19 network 33 ) 20 of 22 practices 21 general 22 practices 22 practices 23 over 23 over 25 period 24 a 25 period 26 of 28 years 27 7 28 years 28 years 30 2002 29 ( 30 2002 30 2002 32 2008 30 2002 33 ) 31 - 32 2008 32 2008 33 ) 34 were 35 analysed multimorbidity was defined as a patient having been diagnosed with two or more of 29 chronic diseases in the general practitioner 's electronic medical records system . 0 ###LEFT-WALL### 1 multimorbidity 0 ###LEFT-WALL### 3 defined 0 ###LEFT-WALL### 27 . 1 multimorbidity 2 was 2 was 3 defined 3 defined 4 as 3 defined 18 in 4 as 12 or 5 a 6 patient 6 patient 7 having 6 patient 12 or 7 having 8 been 8 been 9 diagnosed 9 diagnosed 10 with 10 with 11 two 12 or 17 diseases 13 more 14 of 13 more 17 diseases 14 of 15 29 16 chronic 17 diseases 18 in 26 system 19 the 21 practitioner 20 general 21 practitioner 21 practitioner 22 's 22 's 26 system 23 electronic 25 records 24 medical 25 records 25 records 26 system the prevalence of chronic diseases and multimorbidity was calculated for the total population and subsequently by sex and age groups . 0 ###LEFT-WALL### 2 prevalence 0 ###LEFT-WALL### 9 calculated 0 ###LEFT-WALL### 21 . 1 the 2 prevalence 2 prevalence 3 of 2 prevalence 8 was 3 of 6 and 4 chronic 5 diseases 5 diseases 6 and 6 and 7 multimorbidity 8 was 9 calculated 9 calculated 14 and 10 for 13 population 10 for 14 and 11 the 13 population 12 total 13 population 14 and 15 subsequently 14 and 16 by 16 by 18 and 17 sex 18 and 18 and 20 groups 19 age 20 groups for the 10 most prevalent diseases in the elderly , clustering [and] comorbidity of chronic diseases in patients 55 years and older were analysed . 0 ###LEFT-WALL### 11 clustering 0 ###LEFT-WALL### 23 were 0 ###LEFT-WALL### 25 . 1 for 6 diseases 1 for 10 , 1 for 11 clustering 2 the 3 10 3 10 6 diseases 4 most 5 prevalent 5 prevalent 6 diseases 6 diseases 7 in 7 in 9 elderly 8 the 9 elderly 11 clustering 21 and 11 clustering 23 were 13 comorbidity 14 of 13 comorbidity 21 and 14 of 16 diseases 15 chronic 16 diseases 16 diseases 17 in 17 in 20 years 18 patients 20 years 19 55 20 years 21 and 22 older 23 were 24 analysed results : almost 13 % of the total dutch population and 37 % [of] patients 55 years and older [had] [2] or more chronic diseases . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 26 . 1 results 2 : 2 : 3 almost 3 almost 5 % 4 13 5 % 5 % 6 of 6 of 18 and 7 the 10 population 8 total 10 population 9 dutch 10 population 10 population 11 and 11 and 17 years 11 and 18 and 12 37 17 years 13 % 17 years 15 patients 17 years 16 55 17 years 18 and 25 diseases 19 older 22 or 22 or 23 more 22 or 25 diseases 24 chronic 25 diseases more than 70 % of the patients aged 55 years and older who had 1 of the 10 specific chronic diseases also had an additional chronic disease . 0 ###LEFT-WALL### 4 % 0 ###LEFT-WALL### 23 had 0 ###LEFT-WALL### 28 . 1 more 2 than 2 than 3 70 3 70 4 % 4 % 5 of 4 % 23 had 5 of 7 patients 6 the 7 patients 7 patients 8 aged 7 patients 13 who 7 patients 14 had 8 aged 11 and 9 55 10 years 10 years 11 and 11 and 12 older 13 who 14 had 14 had 15 1 15 1 16 of 16 of 21 diseases 17 the 18 10 18 10 21 diseases 19 specific 21 diseases 20 chronic 21 diseases 22 also 23 had 23 had 27 disease 24 an 25 additional 24 an 27 disease 25 additional 27 disease 26 chronic 27 disease most disease pairs occurred more frequently than expected [based] on independency ( clustering ) , particularly the combinations depression and anxiety disorder , coronary heart disease and heart failure , and copd and heart failure . 0 ###LEFT-WALL### 3 pairs 0 ###LEFT-WALL### 4 occurred 0 ###LEFT-WALL### 7 than 0 ###LEFT-WALL### 36 . 1 most 3 pairs 2 disease 3 pairs 3 pairs 4 occurred 4 occurred 6 frequently 5 more 6 frequently 7 than 20 and 7 than 27 and 8 expected 10 on 8 expected 13 clustering 8 expected 15 , 8 expected 20 and 10 on 11 independency 12 ( 13 clustering 13 clustering 14 ) 16 particularly 20 and 17 the 19 depression 18 combinations 19 depression 19 depression 20 and 20 and 22 disorder 20 and 23 , 20 and 24 coronary 20 and 27 and 21 anxiety 22 disorder 25 heart 26 disease 25 heart 27 and 27 and 33 and 28 heart 31 and 28 heart 33 and 29 failure 31 and 30 , 31 and 31 and 32 copd 33 and 34 heart 34 heart 35 failure the five most common combinations of conditions associated with a certain disease concerned only [a] limited portion ( 30 % ) of all disease comorbidity . 0 ###LEFT-WALL### 5 combinations 0 ###LEFT-WALL### 8 associated 0 ###LEFT-WALL### 26 . 1 the 2 five 2 five 5 combinations 3 most 4 common 4 common 5 combinations 5 combinations 6 of 5 combinations 8 associated 6 of 7 conditions 8 associated 9 with 9 with 17 portion 10 a 11 certain 10 a 17 portion 11 certain 12 disease 12 disease 13 concerned 13 concerned 17 portion 14 only 16 limited 16 limited 17 portion 17 portion 20 % 17 portion 22 of 18 ( 20 % 19 30 20 % 20 % 21 ) 22 of 25 comorbidity 23 all 25 comorbidity 24 disease 25 comorbidity this means that 70 % of patients with a chronic disease had 1 or more additional diseases [not] included in the 5 most frequently occurring diseases . 0 ###LEFT-WALL### 1 this 0 ###LEFT-WALL### 2 means 0 ###LEFT-WALL### 14 or 0 ###LEFT-WALL### 27 . 1 this 2 means 2 means 3 that 3 that 5 % 3 that 12 had 4 70 5 % 5 % 6 of 5 % 12 had 6 of 7 patients 7 patients 8 with 8 with 11 disease 9 a 10 chronic 9 a 11 disease 10 chronic 11 disease 12 had 13 1 14 or 17 diseases 14 or 19 included 15 more 16 additional 16 additional 17 diseases 17 diseases 19 included 19 included 20 in 19 included 26 diseases 20 in 22 5 21 the 22 5 22 5 25 occurring 23 most 24 frequently 24 frequently 25 occurring conclusion : multimorbidity was identified in over two [-] thirds of the elderly with frequently occurring chronic [diseases] . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 3 multimorbidity 2 : 5 identified 2 : 19 . 3 multimorbidity 4 was 4 was 5 identified 5 identified 6 in 5 identified 14 with 5 identified 17 chronic 6 in 10 thirds 7 over 10 thirds 8 two 10 thirds 10 thirds 11 of 11 of 13 elderly 12 the 13 elderly 14 with 16 occurring 15 frequently 16 occurring comorbidity encompassed many different combinations of chronic diseases . 0 ###LEFT-WALL### 1 comorbidity 0 ###LEFT-WALL### 2 encompassed 0 ###LEFT-WALL### 9 . 1 comorbidity 2 encompassed 2 encompassed 5 combinations 3 many 5 combinations 4 different 5 combinations 5 combinations 6 of 6 of 8 diseases 7 chronic 8 diseases in light of an ageing population , multimorbidity should increasingly be taken into account when delivering healthcare , [in] medical research [and] in defining healthcare policies . 0 ###LEFT-WALL### 8 multimorbidity 0 ###LEFT-WALL### 12 taken 0 ###LEFT-WALL### 27 . 1 in 2 light 1 in 7 , 1 in 8 multimorbidity 2 light 3 of 3 of 6 population 4 an 5 ageing 4 an 6 population 5 ageing 6 population 8 multimorbidity 9 should 9 should 11 be 10 increasingly 11 be 11 be 12 taken 12 taken 14 account 12 taken 15 when 12 taken 23 in 13 into 14 account 15 when 16 delivering 16 delivering 21 research 17 healthcare 18 , 17 healthcare 21 research 20 medical 21 research 23 in 24 defining 24 defining 26 policies 25 healthcare 26 policies background : with infertility populations in the developed world rapidly aging , treatment of diminished ovarian reserve ( dor ) assumes increasing clinical importance . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 12 , 0 ###LEFT-WALL### 25 . 1 background 2 : 2 : 3 with 2 : 6 in 3 with 5 populations 4 infertility 5 populations 6 in 9 world 7 the 9 world 8 developed 9 world 9 world 11 aging 10 rapidly 11 aging 12 , 13 treatment 12 , 21 assumes 13 treatment 14 of 13 treatment 19 dor 13 treatment 21 assumes 14 of 17 reserve 15 diminished 17 reserve 16 ovarian 17 reserve 18 ( 19 dor 19 dor 20 ) 21 assumes 22 increasing 22 increasing 24 importance 23 clinical 24 importance dehydroepiandrosterone ( dhea ) has been reported to improve pregnancy chances with dor , and is now utilized by approximately one third of all ivf centers world - wide . 0 ###LEFT-WALL### 3 dhea 0 ###LEFT-WALL### 15 and 0 ###LEFT-WALL### 30 . 1 dehydroepiandrosterone 3 dhea 2 ( 3 dhea 3 dhea 4 ) 3 dhea 15 and 5 has 6 been 5 has 15 and 6 been 7 reported 7 reported 8 to 7 reported 9 improve 8 to 9 improve 9 improve 11 chances 9 improve 12 with 10 pregnancy 11 chances 12 with 13 dor 14 , 15 and 15 and 16 is 16 is 18 utilized 17 now 18 utilized 18 utilized 19 by 18 utilized 28 - 18 utilized 29 wide 19 by 22 third 20 approximately 22 third 21 one 22 third 22 third 23 of 23 of 27 world 24 all 27 world 25 ivf 27 world 26 centers 27 world increasing dhea utilization and publication of a first prospectively randomized trial now warrants a systematic review . 0 ###LEFT-WALL### 1 increasing 0 ###LEFT-WALL### 13 warrants 0 ###LEFT-WALL### 17 . 1 increasing 4 and 1 increasing 13 warrants 2 dhea 3 utilization 3 utilization 4 and 4 and 5 publication 4 and 6 of 6 of 11 trial 7 a 11 trial 8 first 10 randomized 9 prospectively 10 randomized 10 randomized 11 trial 12 now 13 warrants 13 warrants 16 review 14 a 15 systematic 14 a 16 review 15 systematic 16 review methods : pubmed , cochrane and ovid medline were searched between 1995 and 2010 under the following strategy : [ [<] dehydroepiandrosterone or dhea or androgens or testosterone [>] and [<] ovarian reserve or diminished ovarian reserve or ovarian function > ] . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 6 and 2 : 10 searched 2 : 43 . 3 pubmed 4 , 4 , 5 cochrane 4 , 6 and 6 and 8 medline 6 and 9 were 7 ovid 8 medline 9 were 10 searched 10 searched 11 between 10 searched 15 under 11 between 13 and 12 1995 13 and 13 and 14 2010 15 under 17 following 16 the 17 following 17 following 18 strategy 17 following 19 : 17 following 30 and 18 strategy 19 : 20 [ 30 and 22 dehydroepiandrosterone 23 or 23 or 24 dhea 23 or 25 or 25 or 26 androgens 25 or 27 or 27 or 28 testosterone 27 or 30 and 30 and 32 ovarian 30 and 38 or 30 and 41 > 30 and 42 ] 33 reserve 34 or 34 or 37 reserve 34 or 38 or 35 diminished 37 reserve 36 ovarian 37 reserve 38 or 40 function 38 or 41 > 39 ovarian 40 function bibliographies of relevant publications were further explored for additional relevant citations . 0 ###LEFT-WALL### 1 bibliographies 0 ###LEFT-WALL### 7 explored 0 ###LEFT-WALL### 12 . 1 bibliographies 2 of 1 bibliographies 5 were 2 of 4 publications 3 relevant 4 publications 5 were 6 further 5 were 7 explored 7 explored 8 for 8 for 11 citations 9 additional 11 citations 10 relevant 11 citations since only one randomized study has been published , publications , independent of evidence levels and quality assessment , were reviewed . 0 ###LEFT-WALL### 10 publications 0 ###LEFT-WALL### 21 reviewed 0 ###LEFT-WALL### 22 . 1 since 5 study 1 since 8 published 1 since 9 , 1 since 10 publications 2 only 3 one 3 one 5 study 4 randomized 5 study 5 study 6 has 6 has 7 been 7 been 8 published 8 published 9 , 10 publications 16 and 10 publications 20 were 11 , 16 and 12 independent 13 of 12 independent 16 and 13 of 15 levels 14 evidence 15 levels 16 and 18 assessment 16 and 19 , 17 quality 18 assessment 20 were 21 reviewed results : current best available evidence suggests that dhea improves ovarian function [,] increases pregnancy chances [and] , by reducing aneuploidy , lowers miscarriage rates . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 26 . 2 : 3 current 2 : 23 lowers 3 current 6 evidence 3 current 16 chances 3 current 23 lowers 4 best 5 available 5 available 6 evidence 6 evidence 7 suggests 7 suggests 8 that 8 that 9 dhea 8 that 16 chances 9 dhea 10 improves 10 improves 14 increases 11 ovarian 14 increases 12 function 14 increases 15 pregnancy 16 chances 16 chances 19 by 18 , 19 by 19 by 20 reducing 19 by 22 , 20 reducing 21 aneuploidy 23 lowers 25 rates 24 miscarriage 25 rates dhea over time also appears to objectively improve ovarian reserve . 0 ###LEFT-WALL### 1 dhea 0 ###LEFT-WALL### 5 appears 0 ###LEFT-WALL### 11 . 1 dhea 2 over 1 dhea 5 appears 2 over 3 time 4 also 5 appears 5 appears 6 to 5 appears 8 improve 6 to 8 improve 7 objectively 8 improve 8 improve 10 reserve 9 ovarian 10 reserve recent animal data support androgens in promoting preantral follicle growth and reduction in follicle atresia . 0 ###LEFT-WALL### 3 data 0 ###LEFT-WALL### 4 support 0 ###LEFT-WALL### 16 . 1 recent 2 animal 2 animal 3 data 3 data 4 support 4 support 11 and 4 support 13 in 5 androgens 6 in 5 androgens 11 and 6 in 7 promoting 7 promoting 10 growth 8 preantral 10 growth 9 follicle 10 growth 11 and 12 reduction 13 in 15 atresia 14 follicle 15 atresia discussion : improvement of oocyte/embryo quality with dhea supplementation potentially suggests a new concept of ovarian aging , [where] ovarian environments , but not oocytes themselves , age . 0 ###LEFT-WALL### 1 discussion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 27 , 0 ###LEFT-WALL### 29 . 2 : 3 improvement 2 : 11 suggests 3 improvement 4 of 3 improvement 11 suggests 4 of 6 quality 5 oocyte/embryo 6 quality 6 quality 7 with 7 with 9 supplementation 8 dhea 9 supplementation 10 potentially 11 suggests 11 suggests 14 concept 11 suggests 27 , 12 a 13 new 12 a 14 concept 13 new 14 concept 14 concept 15 of 14 concept 23 but 15 of 17 aging 16 ovarian 17 aging 17 aging 21 environments 18 , 21 environments 20 ovarian 21 environments 21 environments 22 , 23 but 24 not 25 oocytes 26 themselves 25 oocytes 27 , 27 , 28 age dhea may , thus , represent a first agent beneficially affecting aging ovarian environments . 0 ###LEFT-WALL### 1 dhea 0 ###LEFT-WALL### 6 represent 0 ###LEFT-WALL### 15 . 1 dhea 2 may 2 may 6 represent 3 , 4 thus 4 thus 5 , 4 thus 6 represent 6 represent 9 agent 7 a 9 agent 8 first 9 agent 9 agent 11 affecting 10 beneficially 11 affecting 11 affecting 14 environments 12 aging 14 environments 13 ovarian 14 environments others can be expected to follow . 0 ###LEFT-WALL### 1 others 0 ###LEFT-WALL### 4 expected 0 ###LEFT-WALL### 7 . 1 others 2 can 2 can 3 be 3 be 4 expected 4 expected 5 to 4 expected 6 follow 5 to 6 follow background : anorectal malformations ( arm ) are rare forms of congenital uro - rectal anomalies with largely unknown causes . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 4 malformations 2 : 8 are 2 : 21 . 3 anorectal 4 malformations 4 malformations 6 arm 4 malformations 8 are 5 ( 6 arm 6 arm 7 ) 8 are 10 forms 9 rare 10 forms 10 forms 11 of 11 of 16 anomalies 12 congenital 16 anomalies 13 uro 14 - 13 uro 16 anomalies 15 rectal 16 anomalies 16 anomalies 17 with 17 with 20 causes 18 largely 19 unknown 19 unknown 20 causes besides genetic factors , prenatal exposures of the parents to nicotine , alcohol , caffeine , illicit drugs , occupational hazards , overweight/obesity and diabetes mellitus are suspected as environmental risk factors . 0 ###LEFT-WALL### 6 exposures 0 ###LEFT-WALL### 28 suspected 0 ###LEFT-WALL### 33 . 1 besides 3 factors 1 besides 4 , 1 besides 6 exposures 2 genetic 3 factors 5 prenatal 6 exposures 6 exposures 7 of 6 exposures 27 are 7 of 9 parents 8 the 9 parents 9 parents 10 to 10 to 24 and 11 nicotine 12 , 12 , 13 alcohol 12 , 14 , 14 , 15 caffeine 14 , 16 , 16 , 18 drugs 16 , 19 , 17 illicit 18 drugs 19 , 21 hazards 19 , 22 , 20 occupational 21 hazards 22 , 23 overweight/obesity 22 , 24 and 24 and 26 mellitus 25 diabetes 26 mellitus 27 are 28 suspected 28 suspected 29 as 29 as 32 factors 30 environmental 32 factors 31 risk 32 factors methods : relevant studies published until august 2010 were identified through systematic search in pubmed , embase , isi web of knowledge and the cochrane library databases . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 13 search 0 ###LEFT-WALL### 28 . 2 : 3 relevant 3 relevant 4 studies 3 relevant 13 search 4 studies 5 published 4 studies 13 search 5 published 6 until 5 published 12 systematic 6 until 7 august 6 until 10 identified 7 august 8 2010 7 august 9 were 9 were 10 identified 10 identified 11 through 13 search 14 in 14 in 23 and 15 pubmed 17 embase 16 , 17 embase 17 embase 18 , 18 , 20 web 18 , 23 and 19 isi 20 web 20 web 21 of 21 of 22 knowledge 23 and 27 databases 24 the 27 databases 25 cochrane 26 library 26 library 27 databases furthermore , related and cross - referencing publications were reviewed . 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 6 - 1 furthermore 2 , 1 furthermore 4 and 3 related 4 and 4 and 5 cross 6 - 7 referencing 6 - 10 reviewed 6 - 11 . 7 referencing 8 publications 7 referencing 9 were 9 were 10 reviewed results : 22 studies that reported on the association between prenatal environmental risk factors and infants born with arm were included in this review . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 25 . 1 results 2 : 2 : 4 studies 3 22 4 studies 4 studies 5 that 4 studies 6 reported 5 that 6 reported 6 reported 7 on 6 reported 15 and 6 reported 21 included 7 on 9 association 8 the 9 association 10 between 13 risk 10 between 15 and 11 prenatal 13 risk 12 environmental 13 risk 14 factors 15 and 15 and 16 infants 15 and 17 born 15 and 20 were 17 born 18 with 18 with 19 arm 20 were 21 included 21 included 22 in 22 in 24 review 23 this 24 review these were conducted in the united states of america ( n = 12 ) , spain ( n = 2 ) , sweden ( n = 2 ) , the netherlands ( n = 2 ) , japan ( n = 1 ) , france ( n = 1 ) , germany ( n = 1 ) and hungary ( n = 1 ) . 0 ###LEFT-WALL### 1 these 0 ###LEFT-WALL### 3 conducted 0 ###LEFT-WALL### 65 . 1 these 2 were 2 were 3 conducted 3 conducted 4 in 4 in 7 states 5 the 7 states 6 united 7 states 7 states 8 of 8 of 9 america 9 america 12 = 9 america 16 spain 9 america 23 sweden 10 ( 12 = 11 n 12 = 12 = 13 12 12 = 14 ) 15 , 16 spain 16 spain 19 = 16 spain 22 , 17 ( 19 = 18 n 19 = 19 = 20 2 19 = 21 ) 22 , 23 sweden 23 sweden 26 = 23 sweden 31 netherlands 23 sweden 64 ) 24 ( 26 = 25 n 26 = 26 = 27 2 26 = 28 ) 29 , 31 netherlands 30 the 31 netherlands 31 netherlands 34 = 31 netherlands 38 japan 31 netherlands 45 france 31 netherlands 64 ) 32 ( 34 = 33 n 34 = 34 = 35 2 34 = 36 ) 37 , 38 japan 38 japan 41 = 38 japan 44 , 39 ( 41 = 40 n 41 = 41 = 42 1 41 = 43 ) 44 , 45 france 45 france 48 = 45 france 58 and 45 france 64 ) 46 ( 48 = 47 n 48 = 48 = 49 1 48 = 50 ) 51 , 58 and 52 germany 55 = 52 germany 58 and 53 ( 55 = 54 n 55 = 55 = 56 1 55 = 57 ) 58 and 59 hungary 58 and 62 = 58 and 64 ) 60 ( 62 = 61 n 62 = 62 = 63 1 62 = 64 ) however , only few of these studies reported on the same risk factors . 0 ###LEFT-WALL### 3 only 0 ###LEFT-WALL### 12 risk 0 ###LEFT-WALL### 14 . 1 however 2 , 1 however 3 only 3 only 4 few 4 few 5 of 4 few 12 risk 5 of 7 studies 6 these 7 studies 7 studies 8 reported 8 reported 9 on 9 on 11 same 10 the 11 same 12 risk 13 factors studies were heterogeneous with respect to case numbers , control types and adjustment for covariates . 0 ###LEFT-WALL### 1 studies 0 ###LEFT-WALL### 2 were 0 ###LEFT-WALL### 9 , 0 ###LEFT-WALL### 16 . 1 studies 2 were 2 were 3 heterogeneous 3 heterogeneous 4 with 3 heterogeneous 6 to 3 heterogeneous 7 case 4 with 5 respect 6 to 7 case 7 case 8 numbers 9 , 12 and 10 control 11 types 11 types 12 and 12 and 13 adjustment 12 and 14 for 14 for 15 covariates consistently increased risks were observed for paternal smoking and maternal overweight , obesity and diabetes , but not for maternal smoking and alcohol consumption . 0 ###LEFT-WALL### 3 risks 0 ###LEFT-WALL### 5 observed 0 ###LEFT-WALL### 25 . 1 consistently 3 risks 2 increased 3 risks 3 risks 4 were 4 were 5 observed 5 observed 17 but 6 for 14 and 6 for 17 but 7 paternal 8 smoking 8 smoking 9 and 9 and 13 obesity 9 and 14 and 10 maternal 13 obesity 11 overweight 12 , 11 overweight 13 obesity 14 and 15 diabetes 14 and 16 , 16 , 17 but 17 but 18 not 17 but 19 for 19 for 22 and 20 maternal 21 smoking 21 smoking 22 and 22 and 24 consumption 23 alcohol 24 consumption in meta - analyses , pooled odds ratios ( 95 % confidence intervals ) for paternal smoking , maternal overweight , obesity , pre - gestational and gestational diabetes were 1.53 ( 1.04 - 2.26 ) , 1.25 ( 1.07 - 1.47 ) , 1.64 ( 1.35 - 2.00 ) , 4.51 ( 2.55 - 7.97 [ )(and 1.81 ( 1.23 - 2.65 ) , respectively . 0 ###LEFT-WALL### 29 diabetes 0 ###LEFT-WALL### 30 were 0 ###LEFT-WALL### 67 . 1 in 8 ratios 1 in 14 ) 1 in 29 diabetes 2 meta 4 analyses 2 meta 5 , 2 meta 8 ratios 3 - 4 analyses 4 analyses 5 , 6 pooled 8 ratios 7 odds 8 ratios 8 ratios 13 intervals 9 ( 13 intervals 10 95 11 % 11 % 12 confidence 12 confidence 13 intervals 13 intervals 14 ) 15 for 17 smoking 15 for 25 - 15 for 29 diabetes 16 paternal 17 smoking 17 smoking 22 obesity 18 , 22 obesity 19 maternal 22 obesity 20 overweight 21 , 20 overweight 22 obesity 22 obesity 24 pre 22 obesity 25 - 23 , 24 pre 24 pre 25 - 26 gestational 27 and 27 and 28 gestational 27 and 29 diabetes 29 diabetes 30 were 30 were 31 1.53 30 were 66 respectively 31 1.53 33 1.04 31 1.53 38 1.25 32 ( 33 1.04 33 1.04 35 2.26 33 1.04 36 ) 34 - 35 2.26 35 2.26 36 ) 37 , 38 1.25 38 1.25 41 - 38 1.25 45 1.64 38 1.25 65 , 39 ( 41 - 40 1.07 41 - 41 - 42 1.47 41 - 43 ) 44 , 45 1.64 45 1.64 47 1.35 45 1.64 65 , 46 ( 47 1.35 47 1.35 49 2.00 47 1.35 52 4.51 47 1.35 65 , 48 - 49 2.00 49 2.00 50 ) 51 , 52 4.51 52 4.51 55 - 52 4.51 65 , 53 ( 55 - 54 2.55 55 - 55 - 58 )(and 55 - 65 , 56 7.97 58 )(and 58 )(and 59 1.81 58 )(and 62 - 60 ( 62 - 61 1.23 62 - 62 - 63 2.65 62 - 64 ) conclusion : evidence on risk factors for arm from epidemiological studies is still very limited . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 3 evidence 2 : 12 is 2 : 16 . 3 evidence 4 on 3 evidence 12 is 4 on 6 factors 5 risk 6 factors 6 factors 7 for 7 for 8 arm 8 arm 9 from 9 from 11 studies 10 epidemiological 11 studies 12 is 13 still 12 is 15 limited 14 very 15 limited nevertheless , the few available studies indicate paternal smoking and maternal overweight , obesity and diabetes to be associated with increased risks . 0 ###LEFT-WALL### 6 studies 0 ###LEFT-WALL### 7 indicate 0 ###LEFT-WALL### 23 . 1 nevertheless 2 , 1 nevertheless 6 studies 3 the 4 few 4 few 6 studies 5 available 6 studies 6 studies 7 indicate 7 indicate 15 and 7 indicate 17 to 8 paternal 9 smoking 9 smoking 10 and 10 and 14 obesity 10 and 15 and 11 maternal 14 obesity 12 overweight 13 , 12 overweight 14 obesity 15 and 16 diabetes 17 to 18 be 18 be 19 associated 19 associated 20 with 20 with 22 risks 21 increased 22 risks further , ideally large - scale multicentre and register - based studies are needed to clarify the role of key risk factors for the development of arm . 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 16 clarify 0 ###LEFT-WALL### 28 . 1 further 2 , 1 further 8 and 3 ideally 8 and 4 large 5 - 4 large 6 scale 6 scale 7 multicentre 7 multicentre 8 and 8 and 9 register 8 and 10 - 8 and 11 based 8 and 12 studies 8 and 15 to 8 and 16 clarify 12 studies 13 are 13 are 14 needed 14 needed 15 to 16 clarify 18 role 17 the 18 role 18 role 19 of 18 role 23 for 18 role 26 of 19 of 22 factors 20 key 22 factors 21 risk 22 factors 23 for 25 development 24 the 25 development 26 of 27 arm background : dark - skinned patients manifest the signs of skin aging differently than their fair - skinned counterparts in that the former exhibit more intrinsic facial aging , whereas the later shows [more] photodamage . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 6 patients 2 : 7 manifest 2 : 36 . 3 dark 4 - 3 dark 6 patients 5 skinned 6 patients 6 patients 7 manifest 7 manifest 9 signs 7 manifest 14 than 8 the 9 signs 9 signs 10 of 10 of 11 skin 11 skin 12 aging 12 aging 13 differently 14 than 19 counterparts 15 their 19 counterparts 16 fair 17 - 16 fair 19 counterparts 18 skinned 19 counterparts 19 counterparts 20 in 19 counterparts 23 former 19 counterparts 35 photodamage 20 in 21 that 22 the 23 former 23 former 24 exhibit 24 exhibit 28 aging 24 exhibit 30 whereas 25 more 28 aging 26 intrinsic 28 aging 27 facial 28 aging 29 , 30 whereas 30 whereas 33 shows 31 the 33 shows 32 later 33 shows 33 shows 35 photodamage nevertheless , common cosmetic procedures can be used in skin of color to treat the signs of aging . 0 ###LEFT-WALL### 5 procedures 0 ###LEFT-WALL### 8 used 0 ###LEFT-WALL### 19 . 1 nevertheless 2 , 1 nevertheless 5 procedures 3 common 5 procedures 4 cosmetic 5 procedures 5 procedures 6 can 6 can 7 be 7 be 8 used 8 used 9 in 8 used 13 to 8 used 14 treat 9 in 10 skin 10 skin 11 of 11 of 12 color 13 to 14 treat 14 treat 16 signs 15 the 16 signs 16 signs 17 of 17 of 18 aging objective : to provide updated clinical information on the use of cosmetic procedures for skin aging in darker phototypes for the safe treatment of this population . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 2 : 3 to 2 : 4 provide 2 : 27 . 3 to 4 provide 4 provide 7 information 4 provide 8 on 4 provide 17 in 5 updated 7 information 6 clinical 7 information 8 on 10 use 9 the 10 use 10 use 11 of 11 of 13 procedures 12 cosmetic 13 procedures 13 procedures 14 for 13 procedures 16 aging 14 for 15 skin 17 in 19 phototypes 18 darker 19 phototypes 19 phototypes 20 for 20 for 23 treatment 21 the 23 treatment 22 safe 23 treatment 23 treatment 24 of 24 of 26 population 25 this 26 population methods : a medline literature search was performed for publications on the safety and efficacy of botulinum toxin , dermal fillers , chemical [peels] , laser and light - based devices , and microdermabrasion for the treatment of skin aging specifically in ethnic populations . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 45 . 2 : 6 search 2 : 8 performed 2 : 19 , 2 : 29 - 3 a 6 search 4 medline 6 search 5 literature 6 search 6 search 7 was 7 was 8 performed 8 performed 9 for 8 performed 11 on 9 for 10 publications 11 on 14 and 12 the 13 safety 13 safety 14 and 14 and 15 efficacy 14 and 16 of 16 of 18 toxin 17 botulinum 18 toxin 19 , 27 and 20 dermal 21 fillers 21 fillers 22 , 22 , 26 laser 22 , 27 and 23 chemical 25 , 23 chemical 26 laser 27 and 28 light 27 and 29 - 29 - 33 and 30 based 31 devices 31 devices 33 and 32 , 33 and 33 and 34 microdermabrasion 34 microdermabrasion 35 for 35 for 37 treatment 36 the 37 treatment 37 treatment 38 of 38 of 39 skin 39 skin 40 aging 39 skin 42 in 40 aging 41 specifically 42 in 44 populations 43 ethnic 44 populations results : similarly to light - skinned patients , botulinum toxin and dermal fillers provide fast , effective results in skin of color , with fewer complications than with traditional surgery and no downtime . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 15 provide 1 results 2 : 2 : 15 provide 3 similarly 4 to 3 similarly 15 provide 4 to 12 and 5 light 8 patients 5 light 9 , 5 light 10 botulinum 6 - 8 patients 7 skinned 8 patients 8 patients 9 , 10 botulinum 11 toxin 11 toxin 12 and 12 and 14 fillers 13 dermal 14 fillers 15 provide 19 results 15 provide 20 in 16 fast 17 , 16 fast 19 results 18 effective 19 results 20 in 21 skin 21 skin 22 of 22 of 23 color 23 color 25 with 24 , 25 with 25 with 27 complications 25 with 28 than 25 with 29 with 25 with 35 . 26 fewer 27 complications 29 with 32 and 30 traditional 31 surgery 31 surgery 32 and 32 and 34 downtime 33 no 34 downtime [more] - invasive procedures , such as chemical peeling , laser resurfacing , and microdermabrasion , can also be effective , but it is important to exercise caution and remain within certain parameters given the greater risk of dyschromias in this population . 0 ###LEFT-WALL### 2 - 0 ###LEFT-WALL### 19 be 0 ###LEFT-WALL### 22 but 0 ###LEFT-WALL### 29 and 0 ###LEFT-WALL### 43 . 2 - 19 be 3 invasive 4 procedures 4 procedures 14 and 4 procedures 17 can 5 , 14 and 6 such 9 peeling 7 as 8 chemical 8 chemical 9 peeling 9 peeling 10 , 10 , 12 resurfacing 10 , 14 and 11 laser 12 resurfacing 13 , 14 and 14 and 15 microdermabrasion 14 and 16 , 17 can 19 be 18 also 19 be 19 be 20 effective 21 , 22 but 22 but 23 it 22 but 24 is 23 it 24 is 24 is 25 important 25 important 26 to 26 to 29 and 27 exercise 28 caution 27 exercise 29 and 29 and 30 remain 29 and 31 within 29 and 40 in 31 within 33 parameters 32 certain 33 parameters 33 parameters 34 given 33 parameters 38 of 34 given 37 risk 35 the 37 risk 36 greater 37 risk 38 of 39 dyschromias 40 in 42 population 41 this 42 population conclusion : with the proper knowledge of how to treat aging skin of color , these patients can experience the benefits of cosmetic procedures while minimizing the risks . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 15 , 0 ###LEFT-WALL### 29 . 1 conclusion 2 : 2 : 3 with 2 : 11 aging 3 with 6 knowledge 4 the 6 knowledge 5 proper 6 knowledge 6 knowledge 7 of 7 of 8 how 8 how 9 to 8 how 10 treat 9 to 10 treat 11 aging 12 skin 12 skin 13 of 13 of 14 color 15 , 17 patients 15 , 19 experience 16 these 17 patients 17 patients 18 can 18 can 19 experience 19 experience 21 benefits 19 experience 25 while 20 the 21 benefits 21 benefits 22 of 22 of 24 procedures 23 cosmetic 24 procedures 25 while 26 minimizing 26 minimizing 28 risks 27 the 28 risks none how service users conceptualise their personal support services is under researched , even though this understanding is important for responsive policy development and service implementation . 0 ###LEFT-WALL### 1 none 0 ###LEFT-WALL### 13 , 0 ###LEFT-WALL### 27 . 1 none 2 how 1 none 11 under 1 none 13 , 2 how 4 users 2 how 5 conceptualise 2 how 10 is 3 service 4 users 4 users 5 conceptualise 5 conceptualise 9 services 6 their 9 services 7 personal 8 support 8 support 9 services 10 is 11 under 12 researched 13 , 13 , 14 even 13 , 26 implementation 14 even 15 though 15 though 17 understanding 15 though 18 is 16 this 17 understanding 17 understanding 18 is 18 is 19 important 19 important 20 for 20 for 24 and 21 responsive 22 policy 22 policy 23 development 23 development 24 and 24 and 25 service this paper tests the proposition that service users understand formal support in three ways : support is a complement to their other arrangements , an intrusion into their personal life and a right . 0 ###LEFT-WALL### 2 paper 0 ###LEFT-WALL### 3 tests 0 ###LEFT-WALL### 15 : 0 ###LEFT-WALL### 34 . 1 this 2 paper 2 paper 3 tests 3 tests 5 proposition 3 tests 12 in 4 the 5 proposition 5 proposition 6 that 5 proposition 9 understand 6 that 8 users 6 that 9 understand 7 service 8 users 8 users 9 understand 9 understand 11 support 10 formal 11 support 12 in 14 ways 13 three 14 ways 15 : 16 support 15 : 17 is 15 : 24 , 16 support 17 is 17 is 19 complement 18 a 19 complement 19 complement 20 to 20 to 23 arrangements 21 their 22 other 22 other 23 arrangements 24 , 31 and 25 an 26 intrusion 26 intrusion 27 into 26 intrusion 31 and 27 into 30 life 28 their 30 life 29 personal 30 life 31 and 33 right 32 a 33 right these three concepts were identified using discourse analysis in a swedish study of older people wanting in [-] home support services . 0 ###LEFT-WALL### 2 three 0 ###LEFT-WALL### 20 support 0 ###LEFT-WALL### 22 . 1 these 2 three 2 three 3 concepts 2 three 16 wanting 2 three 20 support 3 concepts 4 were 4 were 5 identified 5 identified 6 using 5 identified 9 in 6 using 8 analysis 7 discourse 8 analysis 9 in 12 study 10 a 11 swedish 10 a 12 study 11 swedish 12 study 12 study 13 of 12 study 16 wanting 13 of 15 people 14 older 15 people 16 wanting 17 in 17 in 19 home 20 support 21 services to test generalisability of these concepts , they were applied to data from an australian study of people using disability personal support . 0 ###LEFT-WALL### 1 to 0 ###LEFT-WALL### 2 test 0 ###LEFT-WALL### 7 , 0 ###LEFT-WALL### 23 . 1 to 2 test 2 test 3 generalisability 3 generalisability 4 of 4 of 6 concepts 5 these 6 concepts 7 , 8 they 7 , 10 applied 8 they 9 were 9 were 10 applied 10 applied 11 to 11 to 12 data 12 data 13 from 13 from 16 study 14 an 15 australian 14 an 16 study 15 australian 16 study 16 study 17 of 17 of 18 people 18 people 19 using 19 using 22 support 20 disability 22 support 21 personal 22 support the analysis found that the three concepts were core to people 's views of their support , although the construction of the concepts differed in the two countries . 0 ###LEFT-WALL### 2 analysis 0 ###LEFT-WALL### 12 's 1 the 2 analysis 2 analysis 3 found 2 analysis 4 that 2 analysis 9 core 2 analysis 12 's 4 that 7 concepts 4 that 9 core 5 the 6 three 6 three 7 concepts 7 concepts 8 were 8 were 9 core 9 core 10 to 10 to 11 people 12 's 13 views 12 's 18 although 13 views 14 of 14 of 16 support 15 their 16 support 17 , 18 although 18 although 20 construction 18 although 24 differed 18 although 29 . 19 the 20 construction 20 construction 21 of 20 construction 24 differed 21 of 23 concepts 22 the 23 concepts 24 differed 25 in 25 in 28 countries 26 the 27 two 27 two 28 countries service users in sweden asserted their right [to] services more forcefully than those in australia , and they had higher expectations that their support needs would be met . 0 ###LEFT-WALL### 2 users 0 ###LEFT-WALL### 5 asserted 0 ###LEFT-WALL### 12 than 0 ###LEFT-WALL### 29 . 1 service 2 users 2 users 3 in 2 users 5 asserted 3 in 4 sweden 5 asserted 7 right 5 asserted 9 services 6 their 7 right 7 right 9 services 9 services 10 more 9 services 11 forcefully 9 services 12 than 12 than 17 and 12 than 19 had 13 those 14 in 13 those 17 and 14 in 15 australia 16 , 17 and 17 and 18 they 17 and 19 had 19 had 21 expectations 20 higher 21 expectations 21 expectations 22 that 22 that 25 needs 22 that 28 met 23 their 25 needs 24 support 25 needs 25 needs 26 would 26 would 27 be 27 be 28 met these differences reflect the impact of each country 's social policy environment on service users ' expectations . 0 ###LEFT-WALL### 2 differences 0 ###LEFT-WALL### 3 reflect 0 ###LEFT-WALL### 18 . 1 these 2 differences 2 differences 3 reflect 3 reflect 5 impact 3 reflect 13 on 4 the 5 impact 5 impact 6 of 6 of 12 environment 7 each 8 country 8 country 9 's 9 's 12 environment 10 social 11 policy 11 policy 12 environment 13 on 17 expectations 14 service 15 users 15 users 16 ' 16 ' 17 expectations the analysis suggests that service users and their families want to control their formal support arrangements to complement their informal care and their life preferences and to minimise the intrusive aspects of formal support . 0 ###LEFT-WALL### 2 analysis 0 ###LEFT-WALL### 3 suggests 0 ###LEFT-WALL### 35 . 1 the 2 analysis 2 analysis 3 suggests 3 suggests 4 that 4 that 7 and 4 that 10 want 5 service 6 users 6 users 7 and 7 and 9 families 7 and 10 want 8 their 9 families 10 want 11 to 10 want 26 and 11 to 12 control 12 control 16 arrangements 12 control 17 to 13 their 16 arrangements 14 formal 16 arrangements 15 support 16 arrangements 17 to 26 and 18 complement 22 and 18 complement 26 and 19 their 22 and 20 informal 21 care 21 care 22 and 22 and 25 preferences 23 their 25 preferences 24 life 25 preferences 26 and 27 to 26 and 28 minimise 27 to 28 minimise 28 minimise 31 aspects 29 the 31 aspects 30 intrusive 31 aspects 31 aspects 32 of 32 of 34 support 33 formal 34 support the findings imply that the three concepts have utility for theorising service users ' perspectives , informing policy and developing implementation strategies which enhance peoples ' quality of life . 0 ###LEFT-WALL### 2 findings 0 ###LEFT-WALL### 3 imply 1 the 2 findings 2 findings 3 imply 3 imply 4 that 4 that 7 concepts 4 that 8 have 5 the 6 three 6 three 7 concepts 7 concepts 8 have 8 have 9 utility 8 have 10 for 8 have 17 informing 10 for 15 perspectives 11 theorising 12 service 12 service 13 users 13 users 14 ' 14 ' 15 perspectives 16 , 17 informing 17 informing 19 and 17 informing 28 of 17 informing 30 . 18 policy 19 and 19 and 22 strategies 19 and 23 which 19 and 24 enhance 20 developing 21 implementation 21 implementation 22 strategies 23 which 24 enhance 24 enhance 27 quality 25 peoples 26 ' 26 ' 27 quality 28 of 29 life introduction : the clinical and epidemiological data show that proper nutrition plays an important role in maintaining health and combating the danger of developing some chronic diseases in the elderly population . 0 ###LEFT-WALL### 1 introduction 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 32 . 2 : 7 data 2 : 8 show 3 the 7 data 4 clinical 5 and 5 and 6 epidemiological 5 and 7 data 7 data 8 show 8 show 12 plays 8 show 15 role 8 show 19 and 9 that 10 proper 10 proper 11 nutrition 11 nutrition 12 plays 13 an 14 important 13 an 15 role 14 important 15 role 15 role 16 in 16 in 17 maintaining 17 maintaining 18 health 19 and 20 combating 19 and 22 danger 21 the 22 danger 22 danger 23 of 23 of 24 developing 24 developing 27 diseases 25 some 27 diseases 26 chronic 27 diseases 27 diseases 28 in 28 in 31 population 29 the 31 population 30 elderly 31 population nutrition is an important factor in many physiological and pathological changes that accompany the aging process . 0 ###LEFT-WALL### 1 nutrition 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 17 . 1 nutrition 2 is 2 is 5 factor 3 an 5 factor 4 important 5 factor 5 factor 6 in 6 in 11 changes 7 many 11 changes 8 physiological 9 and 9 and 10 pathological 9 and 11 changes 11 changes 12 that 11 changes 13 accompany 12 that 13 accompany 13 accompany 16 process 14 the 16 process 15 aging 16 process more than 50 % of elderly patients are suffering from malnutrition which is information that concerns . 0 ###LEFT-WALL### 4 % 0 ###LEFT-WALL### 8 are 0 ###LEFT-WALL### 17 . 1 more 2 than 2 than 3 50 3 50 4 % 4 % 5 of 4 % 8 are 5 of 7 patients 6 elderly 7 patients 8 are 9 suffering 9 suffering 10 from 10 from 11 malnutrition 11 malnutrition 12 which 11 malnutrition 13 is 12 which 13 is 13 is 14 information 14 information 15 that 14 information 16 concerns 15 that 16 concerns due to various factors , older people are potentially vulnerable groups at risk of malnutrition . 0 ###LEFT-WALL### 7 people 0 ###LEFT-WALL### 8 are 0 ###LEFT-WALL### 16 . 1 due 2 to 2 to 4 factors 2 to 5 , 2 to 7 people 3 various 4 factors 6 older 7 people 7 people 8 are 8 are 9 potentially 8 are 11 groups 10 vulnerable 11 groups 11 groups 12 at 12 at 13 risk 13 risk 14 of 14 of 15 malnutrition loneliness , isolation from society and neglect of parents by children is a big problem to many people in old age . 0 ###LEFT-WALL### 1 loneliness 0 ###LEFT-WALL### 2 , 0 ###LEFT-WALL### 22 . 2 , 3 isolation 2 , 12 is 3 isolation 4 from 3 isolation 8 of 3 isolation 12 is 4 from 6 and 5 society 6 and 6 and 7 neglect 8 of 9 parents 9 parents 10 by 10 by 11 children 12 is 15 problem 13 a 14 big 13 a 15 problem 14 big 15 problem 15 problem 16 to 16 to 18 people 17 many 18 people 18 people 19 in 19 in 21 age 20 old 21 age objective : to determine differences in nutritional status of elderly people living alone compared to those who live in family surroundings . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 22 . 2 : 3 to 2 : 4 determine 3 to 4 determine 4 determine 5 differences 5 differences 6 in 5 differences 9 of 6 in 8 status 7 nutritional 8 status 9 of 11 people 10 elderly 11 people 11 people 12 living 11 people 14 compared 11 people 17 who 11 people 18 live 13 alone 14 compared 14 compared 15 to 15 to 16 those 17 who 18 live 18 live 19 in 19 in 21 surroundings 20 family 21 surroundings subject and methods : the study was conducted in the municipality of tuzla in 2009 - 2010 , in outpatient family medicine simin han . 0 ###LEFT-WALL### 3 methods 0 ###LEFT-WALL### 4 : 0 ###LEFT-WALL### 25 . 1 subject 2 and 2 and 3 methods 4 : 6 study 4 : 8 conducted 5 the 6 study 6 study 7 was 7 was 8 conducted 8 conducted 9 in 8 conducted 14 in 8 conducted 19 in 9 in 11 municipality 10 the 11 municipality 11 municipality 12 of 12 of 13 tuzla 14 in 15 2009 15 2009 17 2010 16 - 17 2010 17 2010 18 , 19 in 24 han 20 outpatient 22 medicine 21 family 22 medicine 22 medicine 24 han 23 simin 24 han the survey covered a total of 200 elderly subjects ( age >65 years ) . 0 ###LEFT-WALL### 2 survey 0 ###LEFT-WALL### 3 covered 0 ###LEFT-WALL### 15 . 1 the 2 survey 2 survey 3 covered 3 covered 5 total 4 a 5 total 5 total 6 of 6 of 9 subjects 7 200 9 subjects 8 elderly 9 subjects 9 subjects 13 years 10 ( 13 years 11 age 13 years 12 >65 13 years 13 years 14 ) subject group [consisted] of 45 % of people living alone , and 55 % control group consisted of elderly patients who live in traditional family surroundings . 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 17 consisted 0 ###LEFT-WALL### 27 . 1 subject 2 group 2 group 4 of 2 group 12 and 4 of 6 % 5 45 6 % 6 % 7 of 6 % 9 living 7 of 8 people 9 living 10 alone 11 , 12 and 12 and 16 group 12 and 17 consisted 13 55 14 % 14 % 15 control 15 control 16 group 17 consisted 18 of 18 of 20 patients 19 elderly 20 patients 20 patients 21 who 20 patients 22 live 21 who 22 live 22 live 23 in 23 in 26 surroundings 24 traditional 25 family 25 family 26 surroundings questionnaires used in this study [are] general geriatric assessment questionnaire and mini nutritional status . 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 15 . 1 questionnaires 2 used 1 questionnaires 11 and 2 used 3 in 3 in 10 questionnaire 4 this 10 questionnaire 5 study 10 questionnaire 7 general 10 questionnaire 8 geriatric 9 assessment 9 assessment 10 questionnaire 11 and 14 status 12 mini 14 status 13 nutritional 14 status results : the average age ( +/ - sd ) [was] 75.4 +/ - 6.2 [years] in subject group , while the same in the control group was 74.9 +/ - 5.6 years . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 14 - 1 results 2 : 2 : 5 age 3 the 5 age 4 average 5 age 5 age 13 +/ 6 ( 13 +/ 7 +/ 9 sd 7 +/ 13 +/ 8 - 9 sd 9 sd 10 ) 12 75.4 13 +/ 13 +/ 14 - 14 - 19 group 14 - 20 , 14 - 34 . 15 6.2 17 in 17 in 18 subject 18 subject 19 group 20 , 29 74.9 20 , 30 +/ 21 while 23 same 21 while 28 was 21 while 29 74.9 22 the 23 same 23 same 24 in 23 same 28 was 24 in 27 group 25 the 27 group 26 control 27 group 29 74.9 30 +/ 30 +/ 33 years 31 - 32 5.6 32 5.6 33 years in [subject] [group] significantly more patients are on the verge of poverty . 0 ###LEFT-WALL### 6 patients 0 ###LEFT-WALL### 7 are 0 ###LEFT-WALL### 13 . 1 in 5 more 1 in 6 patients 4 significantly 5 more 6 patients 7 are 7 are 8 on 8 on 10 verge 9 the 10 verge 10 verge 11 of 11 of 12 poverty there are significant differences in the classification of financial status , according to the groups ( p = 0.043 ) . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 are 0 ###LEFT-WALL### 21 . 1 there 2 are 2 are 4 differences 2 are 5 in 2 are 13 to 3 significant 4 differences 5 in 7 classification 6 the 7 classification 7 classification 8 of 8 of 10 status 9 financial 10 status 11 , 13 to 12 according 13 to 13 to 15 groups 13 to 20 ) 14 the 15 groups 15 groups 18 = 16 ( 18 = 17 p 18 = 18 = 19 0.043 members of subject groups have significantly lower bmi categories ( p = 0.03 ) compared with the control group . 0 ###LEFT-WALL### 1 members 0 ###LEFT-WALL### 5 have 0 ###LEFT-WALL### 20 . 1 members 2 of 1 members 5 have 2 of 4 groups 3 subject 4 groups 5 have 9 categories 5 have 15 compared 6 significantly 7 lower 7 lower 9 categories 8 bmi 9 categories 9 categories 12 = 10 ( 12 = 11 p 12 = 12 = 13 0.03 12 = 14 ) 15 compared 16 with 16 with 19 group 17 the 19 group 18 control 19 group in our study , people who live alone are at increased risk of malnutrition ( p = 0030 ) , have reduced the number of daily meals , significantly lower daily intake of protein , fruits and vegetables in the diet in relation to persons living in a family environment . 0 ###LEFT-WALL### 5 people 0 ###LEFT-WALL### 9 are 0 ###LEFT-WALL### 20 , 0 ###LEFT-WALL### 51 . 1 in 3 study 1 in 4 , 1 in 5 people 2 our 3 study 5 people 6 who 5 people 7 live 5 people 9 are 6 who 7 live 8 alone 9 are 9 are 10 at 9 are 17 = 10 at 12 risk 11 increased 12 risk 12 risk 13 of 13 of 14 malnutrition 15 ( 17 = 16 p 17 = 17 = 18 0030 17 = 19 ) 20 , 28 , 21 have 22 reduced 21 have 28 , 22 reduced 27 meals 23 the 24 number 24 number 25 of 24 number 27 meals 25 of 27 meals 26 daily 27 meals 28 , 30 lower 29 significantly 30 lower 30 lower 32 intake 30 lower 39 in 30 lower 42 in 31 daily 32 intake 32 intake 33 of 33 of 37 and 34 protein 35 , 35 , 36 fruits 35 , 37 and 37 and 38 vegetables 39 in 41 diet 40 the 41 diet 42 in 43 relation 43 relation 44 to 43 relation 46 living 44 to 45 persons 46 living 47 in 47 in 50 environment 48 a 50 environment 49 family 50 environment significantly more patients with loss of appetite live alone . 0 ###LEFT-WALL### 3 patients 0 ###LEFT-WALL### 8 live 0 ###LEFT-WALL### 10 . 1 significantly 2 more 2 more 3 patients 3 patients 4 with 3 patients 8 live 4 with 5 loss 5 loss 6 of 6 of 7 appetite 8 live 9 alone according to the existence [of] self - reported food problems significantly more people are in subject group . 0 ###LEFT-WALL### 17 group 0 ###LEFT-WALL### 18 . 1 according 2 to 2 to 6 self 2 to 17 group 3 the 6 self 4 existence 6 self 7 - 8 reported 8 reported 9 food 8 reported 17 group 9 food 10 problems 9 food 16 subject 10 problems 13 people 10 problems 15 in 10 problems 16 subject 11 significantly 12 more 12 more 13 people 13 people 14 are 14 are 15 in there is a difference value score " small assessment of nutrition " between the two groups ( p = 0.001 ) . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 22 . 1 there 2 is 2 is 9 assessment 3 a 9 assessment 4 difference 9 assessment 5 value 9 assessment 6 score 7 " 6 score 9 assessment 8 small 9 assessment 9 assessment 10 of 9 assessment 13 between 9 assessment 19 = 10 of 11 nutrition 11 nutrition 12 " 13 between 16 groups 14 the 15 two 15 two 16 groups 17 ( 19 = 18 p 19 = 19 = 20 0.001 19 = 21 ) about 22 % of the total number of respondents said they have not so good health status compared to others . 0 ###LEFT-WALL### 17 status 0 ###LEFT-WALL### 18 compared 0 ###LEFT-WALL### 21 . 1 about 3 % 1 about 17 status 2 22 3 % 3 % 4 of 3 % 11 they 3 % 12 have 4 of 9 respondents 5 the 7 number 6 total 7 number 7 number 8 of 7 number 9 respondents 8 of 9 respondents 9 respondents 10 said 11 they 12 have 13 not 16 health 13 not 17 status 14 so 15 good 15 good 16 health 17 status 18 compared 18 compared 19 to 19 to 20 others conclusions : loneliness is a significant predictor of anorexia nervosa , the risk of malnutrition and malnutrition . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 18 . 2 : 3 loneliness 2 : 4 is 2 : 11 , 3 loneliness 4 is 4 is 7 predictor 5 a 6 significant 5 a 7 predictor 6 significant 7 predictor 7 predictor 8 of 8 of 10 nervosa 9 anorexia 10 nervosa 11 , 16 and 12 the 13 risk 13 risk 14 of 13 risk 16 and 14 of 15 malnutrition 16 and 17 malnutrition results indicate that it is necessary to work on improving the status and protection of [elderly] . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 indicate 0 ###LEFT-WALL### 17 . 1 results 2 indicate 2 indicate 3 that 3 that 4 it 3 that 5 is 4 it 5 is 5 is 6 necessary 6 necessary 7 to 6 necessary 15 of 7 to 8 work 8 work 9 on 8 work 13 and 9 on 10 improving 11 the 12 status 12 status 13 and 13 and 14 protection 14 protection 15 of in clinical decision [-] making on whether or not to treat an oral disease and on making a choice from the spectrum of treatment options , the influence of the treatment on the physical and psycho - social well - being of the patient should play a crucial role . 0 ###LEFT-WALL### 26 , 0 ###LEFT-WALL### 50 . 1 in 5 making 1 in 26 , 2 clinical 5 making 3 decision 5 making 5 making 15 and 5 making 20 from 6 on 9 not 6 on 15 and 7 whether 8 or 8 or 9 not 9 not 10 to 9 not 11 treat 10 to 11 treat 11 treat 14 disease 12 an 14 disease 13 oral 14 disease 15 and 16 on 16 on 17 making 17 making 19 choice 18 a 19 choice 20 from 22 spectrum 21 the 22 spectrum 22 spectrum 23 of 23 of 24 treatment 25 options 26 , 26 , 46 play 27 the 28 influence 28 influence 29 of 28 influence 35 and 29 of 31 treatment 30 the 31 treatment 31 treatment 32 on 32 on 34 physical 33 the 34 physical 35 and 39 well 35 and 40 - 35 and 41 being 35 and 45 should 36 psycho 37 - 36 psycho 39 well 38 social 39 well 41 being 42 of 42 of 44 patient 43 the 44 patient 45 should 46 play 46 play 49 role 47 a 48 crucial 47 a 49 role 48 crucial 49 role this awareness originates from gerodontology . 0 ###LEFT-WALL### 2 awareness 0 ###LEFT-WALL### 3 originates 0 ###LEFT-WALL### 6 . 1 this 2 awareness 2 awareness 3 originates 3 originates 4 from 4 from 5 gerodontology to assess the value of a potential treatment , the concept quality of life has been advanced and various related questionnaires have been developed and employed . 0 ###LEFT-WALL### 1 to 0 ###LEFT-WALL### 9 , 0 ###LEFT-WALL### 27 . 1 to 9 , 2 assess 4 value 2 assess 9 , 3 the 4 value 4 value 5 of 5 of 8 treatment 6 a 7 potential 6 a 8 treatment 7 potential 8 treatment 9 , 18 and 10 the 12 quality 11 concept 12 quality 12 quality 13 of 12 quality 15 has 13 of 14 life 15 has 16 been 16 been 18 and 17 advanced 18 and 18 and 25 and 19 various 21 questionnaires 20 related 21 questionnaires 21 questionnaires 22 have 22 have 23 been 23 been 25 and 24 developed 25 and 25 and 26 employed in the meantime , doubts have arisen about the value of these questionnaires . 0 ###LEFT-WALL### 5 doubts 0 ###LEFT-WALL### 7 arisen 0 ###LEFT-WALL### 14 . 1 in 3 meantime 1 in 4 , 1 in 5 doubts 2 the 3 meantime 5 doubts 6 have 6 have 7 arisen 7 arisen 8 about 8 about 10 value 9 the 10 value 10 value 11 of 11 of 13 questionnaires 12 these 13 questionnaires the present - day trend is to return to so - called qualitative research , which consists of systematic interviews of groups of older people using open - ended questions without making use of structured response options . 0 ###LEFT-WALL### 5 trend 0 ###LEFT-WALL### 6 is 0 ###LEFT-WALL### 15 , 0 ###LEFT-WALL### 38 . 1 the 5 trend 2 present 3 - 2 present 5 trend 4 day 5 trend 5 trend 6 is 6 is 7 to 7 to 8 return 8 return 9 to 8 return 12 called 9 to 10 so 11 - 12 called 12 called 14 research 12 called 15 , 13 qualitative 14 research 15 , 16 which 15 , 17 consists 16 which 17 consists 17 consists 18 of 18 of 20 interviews 19 systematic 20 interviews 20 interviews 21 of 20 interviews 31 without 21 of 22 groups 22 groups 23 of 22 groups 26 using 23 of 25 people 24 older 25 people 26 using 30 questions 27 open 28 - 27 open 30 questions 29 ended 30 questions 31 without 32 making 32 making 33 use 33 use 34 of 34 of 37 options 35 structured 37 options 36 response 37 options none objectives : to investigate the age - related alterations in functional visual acuity ( fva ) in healthy individuals . 0 ###LEFT-WALL### 1 none 0 ###LEFT-WALL### 5 investigate 0 ###LEFT-WALL### 9 related 1 none 2 objectives 1 none 4 to 1 none 5 investigate 2 objectives 3 : 3 : 4 to 5 investigate 7 age 6 the 7 age 8 - 9 related 9 related 10 alterations 9 related 11 in 9 related 18 in 9 related 21 . 11 in 14 acuity 12 functional 14 acuity 13 visual 14 acuity 14 acuity 16 fva 15 ( 16 fva 16 fva 17 ) 18 in 20 individuals 19 healthy 20 individuals design : a prospective [non] - comparative multi - center study . 0 ###LEFT-WALL### 1 design 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 12 . 1 design 2 : 2 : 11 study 3 a 4 prospective 3 a 11 study 4 prospective 6 - 4 prospective 7 comparative 7 comparative 11 study 8 multi 9 - 8 multi 10 center 10 center 11 study setting and participants : fifty - four eyes of 54 normal subjects with best corrected visual acuities better than 20/20 seen at the outpatient clinics of the department of ophthalmology at keio university , minamiaoyama eye clinic and ishida eye clinic were studied . 0 ###LEFT-WALL### 1 setting 0 ###LEFT-WALL### 44 . 1 setting 3 participants 1 setting 13 with 1 setting 15 corrected 2 and 3 participants 3 participants 4 : 4 : 8 eyes 4 : 13 with 5 fifty 6 - 6 - 7 four 6 - 8 eyes 8 eyes 9 of 9 of 12 subjects 10 54 12 subjects 11 normal 12 subjects 14 best 15 corrected 15 corrected 17 acuities 15 corrected 18 better 15 corrected 19 than 16 visual 17 acuities 19 than 20 20/20 19 than 43 studied 20 20/20 21 seen 20 20/20 22 at 20 20/20 26 of 20 20/20 31 at 20 20/20 42 were 22 at 25 clinics 23 the 25 clinics 24 outpatient 25 clinics 26 of 28 department 27 the 28 department 28 department 29 of 29 of 30 ophthalmology 31 at 38 and 32 keio 33 university 33 university 34 , 34 , 37 clinic 34 , 38 and 35 minamiaoyama 36 eye 36 eye 37 clinic 38 and 41 clinic 39 ishida 40 eye 40 eye 41 clinic 42 were 43 studied measurements : fva measurements , schirmer test , but , tear clearance rate and fluorescein vital staining scores were obtained . 0 ###LEFT-WALL### 1 measurements 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 5 , 0 ###LEFT-WALL### 21 . 1 measurements 2 : 2 : 4 measurements 3 fva 4 measurements 5 , 7 test 5 , 8 , 6 schirmer 7 test 8 , 14 and 8 , 20 obtained 9 but 10 , 10 , 13 rate 10 , 14 and 11 tear 12 clearance 12 clearance 13 rate 14 and 15 fluorescein 14 and 17 staining 14 and 18 scores 14 and 19 were 16 vital 17 staining 17 staining 18 scores 19 were 20 obtained results : schirmer test scores , but values and fluorescein vital staining scores did not show significant changes ( p > 0.05 ) , but there were significant differences in tear clearance rates among the age groups ( p < 0.05 ) . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 4 test 2 : 24 , 2 : 27 were 2 : 43 . 3 schirmer 4 test 4 test 5 scores 5 scores 9 and 6 , 9 and 7 but 8 values 8 values 9 and 9 and 10 fluorescein 9 and 13 scores 9 and 16 show 9 and 21 > 9 and 24 , 11 vital 13 scores 12 staining 13 scores 13 scores 14 did 14 did 15 not 14 did 16 show 16 show 18 changes 17 significant 18 changes 19 ( 21 > 20 p 21 > 21 > 22 0.05 21 > 23 ) 24 , 25 but 24 , 27 were 25 but 26 there 25 but 27 were 27 were 29 differences 28 significant 29 differences 29 differences 30 in 30 in 33 rates 31 tear 32 clearance 32 clearance 33 rates 33 rates 34 among 34 among 37 groups 35 the 37 groups 36 age 37 groups 37 groups 40 < 38 ( 40 < 39 p 40 < 40 < 41 0.05 40 < 42 ) tear function index , which is a value obtained from multiplying a schirmer test score by the tear clearance rate , also showed significant differences in the age groups ( p < 0.05 ) . 0 ###LEFT-WALL### 3 index 0 ###LEFT-WALL### 4 , 0 ###LEFT-WALL### 35 . 1 tear 2 function 2 function 3 index 4 , 5 which 4 , 21 , 5 which 21 , 6 is 8 value 6 is 21 , 7 a 8 value 8 value 9 obtained 9 obtained 10 from 9 obtained 16 by 10 from 11 multiplying 11 multiplying 15 score 12 a 15 score 13 schirmer 14 test 14 test 15 score 16 by 20 rate 17 the 20 rate 18 tear 19 clearance 19 clearance 20 rate 21 , 23 showed 21 , 25 differences 22 also 23 showed 24 significant 25 differences 25 differences 26 in 25 differences 32 < 26 in 29 groups 27 the 29 groups 28 age 29 groups 30 ( 32 < 31 p 32 < 32 < 33 0.05 32 < 34 ) the mean logmar fva score decreased significantly in the older groups ( p < 0.05 ) , while the mean conventional va score did not show significant differences among the age groups . 0 ###LEFT-WALL### 5 score 0 ###LEFT-WALL### 6 decreased 1 the 5 score 2 mean 3 logmar 3 logmar 5 score 4 fva 5 score 5 score 6 decreased 6 decreased 7 significantly 6 decreased 8 in 6 decreased 18 while 8 in 11 groups 9 the 11 groups 10 older 11 groups 11 groups 14 < 12 ( 14 < 13 p 14 < 14 < 15 0.05 14 < 16 ) 17 , 18 while 18 while 23 score 18 while 26 show 18 while 33 . 19 the 23 score 20 mean 23 score 21 conventional 23 score 22 va 23 score 23 score 24 did 24 did 25 not 24 did 26 show 26 show 28 differences 26 show 29 among 27 significant 28 differences 29 among 32 groups 30 the 32 groups 31 age 32 groups moreover , there were significantly more eyes with lower minimum va scores in the older age groups ( p < 0.05 ) . 0 ###LEFT-WALL### 3 there 0 ###LEFT-WALL### 4 were 0 ###LEFT-WALL### 23 . 1 moreover 2 , 1 moreover 3 there 3 there 4 were 4 were 7 eyes 5 significantly 6 more 6 more 7 eyes 7 eyes 8 with 7 eyes 13 in 8 with 12 scores 9 lower 10 minimum 10 minimum 12 scores 11 va 12 scores 13 in 17 groups 14 the 17 groups 15 older 16 age 16 age 17 groups 17 groups 20 < 18 ( 20 < 19 p 20 < 20 < 21 0.05 20 < 22 ) logmar minimum va appeared to be significantly related to the tear clearance rates in subjects 60 years and older ( p < 0.05 ) . 0 ###LEFT-WALL### 6 be 0 ###LEFT-WALL### 25 . 1 logmar 3 va 2 minimum 3 va 3 va 4 appeared 4 appeared 5 to 5 to 6 be 6 be 7 significantly 6 be 8 related 8 related 9 to 8 related 14 in 8 related 18 and 9 to 13 rates 10 the 13 rates 11 tear 13 rates 12 clearance 13 rates 14 in 15 subjects 15 subjects 16 60 17 years 18 and 18 and 19 older 19 older 22 < 20 ( 22 < 21 p 22 < 22 < 23 0.05 22 < 24 ) conclusions : fva testing seems to be a useful method of assessing the age - related decline [in] dynamic visual and tear functions . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 16 related 0 ###LEFT-WALL### 24 . 1 conclusions 2 : 2 : 3 fva 3 fva 4 testing 3 fva 12 assessing 4 testing 5 seems 5 seems 6 to 5 seems 7 be 6 to 7 be 7 be 10 method 8 a 10 method 9 useful 10 method 10 method 11 of 11 of 12 assessing 12 assessing 14 age 13 the 14 age 15 - 16 related 16 related 23 functions 17 decline 23 functions 19 dynamic 23 functions 20 visual 21 and 21 and 22 tear 21 and 23 functions the current study examines the eeg coherence of young , old , and old declined adults performing a visual paired [-] associates task . 0 ###LEFT-WALL### 3 study 0 ###LEFT-WALL### 4 examines 0 ###LEFT-WALL### 24 . 1 the 3 study 2 current 3 study 3 study 4 examines 4 examines 7 coherence 4 examines 15 declined 5 the 7 coherence 6 eeg 7 coherence 7 coherence 8 of 7 coherence 15 declined 8 of 13 and 9 young 10 , 10 , 11 old 10 , 13 and 12 , 13 and 13 and 14 old 15 declined 16 adults 16 adults 17 performing 17 performing 23 task 18 a 19 visual 18 a 23 task 19 visual 22 associates 20 paired 22 associates 22 associates 23 task in order to examine the effects of encoding context and stimulus repetition , target pairs were presented on either detailed or white backgrounds and were repeatedly presented during both early and late phases of encoding . 0 ###LEFT-WALL### 15 pairs 0 ###LEFT-WALL### 24 and 0 ###LEFT-WALL### 36 . 1 in 2 order 1 in 15 pairs 3 to 4 examine 3 to 13 , 3 to 15 pairs 4 examine 10 and 5 the 10 and 6 effects 7 of 6 effects 10 and 7 of 8 encoding 8 encoding 9 context 10 and 12 repetition 11 stimulus 12 repetition 14 target 15 pairs 15 pairs 24 and 16 were 17 presented 16 were 24 and 17 presented 18 on 18 on 23 backgrounds 19 either 21 or 20 detailed 21 or 21 or 22 white 21 or 23 backgrounds 24 and 25 were 24 and 33 phases 25 were 27 presented 26 repeatedly 27 presented 27 presented 28 during 27 presented 31 and 28 during 29 both 30 early 31 and 31 and 32 late 33 phases 34 of 34 of 35 encoding younger adults were found to have lower levels of frontal - temporal and temporal - parietal coherence , but higher levels of frontal - parietal coherence , particularly for the gamma frequency band . 0 ###LEFT-WALL### 2 adults 0 ###LEFT-WALL### 6 have 0 ###LEFT-WALL### 34 . 1 younger 2 adults 2 adults 3 were 3 were 4 found 4 found 5 to 5 to 6 have 6 have 8 levels 6 have 28 particularly 7 lower 8 levels 8 levels 9 of 9 of 17 coherence 10 frontal 13 and 10 frontal 17 coherence 11 - 13 and 12 temporal 13 and 13 and 14 temporal 13 and 15 - 16 parietal 17 coherence 17 coherence 19 but 18 , 19 but 19 but 21 levels 19 but 27 , 20 higher 21 levels 21 levels 22 of 22 of 26 coherence 23 frontal 24 - 23 frontal 26 coherence 25 parietal 26 coherence 28 particularly 29 for 29 for 33 band 30 the 33 band 31 gamma 33 band 32 frequency 33 band a number of differential coherence responses to background context and early - versus late - encoding phases were also observed across the groups , particularly for lower alpha and upper alpha frequencies . 0 ###LEFT-WALL### 6 responses 0 ###LEFT-WALL### 20 observed 1 a 2 number 2 number 3 of 2 number 6 responses 3 of 6 responses 4 differential 5 coherence 5 coherence 6 responses 6 responses 7 to 6 responses 18 were 7 to 10 and 8 background 9 context 9 context 10 and 10 and 11 early 10 and 12 - 10 and 13 versus 13 versus 17 phases 14 late 15 - 14 late 16 encoding 16 encoding 17 phases 18 were 19 also 18 were 20 observed 20 observed 21 across 20 observed 26 for 21 across 23 groups 22 the 23 groups 24 , 25 particularly 24 , 26 for 26 for 29 and 26 for 33 . 27 lower 28 alpha 28 alpha 29 and 29 and 32 frequencies 30 upper 31 alpha 31 alpha 32 frequencies [coherence] - performance maps were generated to further explore topographical differences in the relationship between coherence and performance across groups . 0 ###LEFT-WALL### 2 - 0 ###LEFT-WALL### 6 generated 0 ###LEFT-WALL### 21 . 2 - 4 maps 3 performance 4 maps 4 maps 5 were 5 were 6 generated 6 generated 7 to 6 generated 15 between 7 to 9 explore 8 further 9 explore 9 explore 11 differences 9 explore 12 in 10 topographical 11 differences 12 in 14 relationship 13 the 14 relationship 15 between 17 and 16 coherence 17 and 17 and 18 performance 17 and 19 across 19 across 20 groups results revealed a more diffuse pattern of negative coherence - performance relations in older [declined] adults . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 revealed 0 ###LEFT-WALL### 10 - 0 ###LEFT-WALL### 17 . 1 results 2 revealed 2 revealed 6 pattern 3 a 6 pattern 4 more 5 diffuse 5 diffuse 6 pattern 6 pattern 7 of 7 of 9 coherence 8 negative 9 coherence 10 - 12 relations 11 performance 12 relations 12 relations 13 in 13 in 16 adults 14 older 16 adults results are discussed in light of the literature on age - related cognitive decline . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 3 discussed 0 ###LEFT-WALL### 11 - 1 results 2 are 2 are 3 discussed 3 discussed 4 in 3 discussed 9 on 4 in 5 light 5 light 6 of 6 of 8 literature 7 the 8 literature 9 on 10 age 11 - 14 decline 11 - 15 . 12 related 14 decline 13 cognitive 14 decline the proteasomal degradation of cytosolic , phosphorylation - independent tau in human brains is potentially linked to the pathogenesis of neurofibrillary pathology in alzheimer 's disease ( ad ) . 0 ###LEFT-WALL### 3 degradation 0 ###LEFT-WALL### 16 linked 0 ###LEFT-WALL### 30 . 1 the 3 degradation 2 proteasomal 3 degradation 3 degradation 4 of 3 degradation 14 is 4 of 10 tau 5 cytosolic 7 phosphorylation 5 cytosolic 10 tau 6 , 7 phosphorylation 7 phosphorylation 8 - 9 independent 10 tau 10 tau 11 in 11 in 13 brains 12 human 13 brains 14 is 16 linked 15 potentially 16 linked 16 linked 17 to 16 linked 23 in 17 to 19 pathogenesis 18 the 19 pathogenesis 19 pathogenesis 20 of 20 of 22 pathology 21 neurofibrillary 22 pathology 23 in 26 disease 24 alzheimer 25 's 25 's 26 disease 26 disease 28 ad 27 ( 28 ad 28 ad 29 ) previous studies showed that the active 20 s proteasome core degrades recombinant tau effectively , which prompted this study to determine if there was evidence of proteasomal degradation of tau in human brain with a range of neurofibrillary pathology . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 3 showed 0 ###LEFT-WALL### 15 , 0 ###LEFT-WALL### 40 . 1 previous 2 studies 2 studies 3 showed 3 showed 4 that 3 showed 10 core 3 showed 11 degrades 5 the 10 core 6 active 10 core 7 20 8 s 8 s 10 core 9 proteasome 10 core 10 core 11 degrades 11 degrades 13 tau 11 degrades 14 effectively 12 recombinant 13 tau 15 , 16 which 15 , 17 prompted 16 which 17 prompted 17 prompted 19 study 17 prompted 20 to 17 prompted 21 determine 18 this 19 study 20 to 21 determine 21 determine 22 if 22 if 23 there 22 if 24 was 23 there 24 was 24 was 25 evidence 25 evidence 26 of 25 evidence 29 of 26 of 28 degradation 27 proteasomal 28 degradation 29 of 30 tau 30 tau 31 in 30 tau 37 of 31 in 33 brain 32 human 33 brain 33 brain 34 with 34 with 36 range 35 a 36 range 37 of 39 pathology 38 neurofibrillary 39 pathology cytosolic proteins from temporal cortex [were] isolated [from] 30,000xgsupernatants by resolving in size - exclusion chromatogra - phy for assay [of] tau and proteasomal subunits by western blots . 0 ###LEFT-WALL### 23 and 0 ###LEFT-WALL### 29 . 1 cytosolic 2 proteins 2 proteins 3 from 2 proteins 10 by 2 proteins 12 in 2 proteins 18 phy 2 proteins 23 and 3 from 9 30,000xgsupernatants 4 temporal 9 30,000xgsupernatants 5 cortex 7 isolated 7 isolated 9 30,000xgsupernatants 10 by 11 resolving 12 in 13 size 13 size 16 chromatogra 14 - 16 chromatogra 15 exclusion 16 chromatogra 16 chromatogra 17 - 18 phy 19 for 19 for 22 tau 20 assay 22 tau 23 and 25 subunits 24 proteasomal 25 subunits 25 subunits 26 by 26 by 28 blots 27 western 28 blots levels of tau and proteasome subunits varied from case to case , with a significant inverse correlation between the levels of tau and 20 s β - subunits , and between 70 - [kda] tau and 11s β - subunits , suggesting that tau is a proteasomal substrate . 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 9 case 1 levels 2 of 1 levels 4 and 2 of 3 tau 4 and 5 proteasome 4 and 6 subunits 4 and 8 from 4 and 9 case 6 subunits 7 varied 7 varied 8 from 9 case 10 to 9 case 38 β 9 case 42 suggesting 10 to 11 case 11 case 13 with 11 case 36 and 12 , 13 with 13 with 17 correlation 13 with 33 - 14 a 17 correlation 15 significant 17 correlation 16 inverse 17 correlation 17 correlation 30 and 18 between 23 and 18 between 30 and 19 the 20 levels 20 levels 21 of 20 levels 23 and 21 of 22 tau 23 and 26 β 23 and 28 subunits 24 20 25 s 25 s 26 β 27 - 28 subunits 28 subunits 29 , 29 , 30 and 30 and 31 between 31 between 32 70 35 tau 36 and 36 and 37 11s 38 β 40 subunits 39 - 40 subunits 40 subunits 41 , 41 , 42 suggesting 42 suggesting 43 that 42 suggesting 49 . 43 that 44 tau 43 that 45 is 44 tau 45 is 45 is 48 substrate 46 a 48 substrate 47 proteasomal 48 substrate the inability to detect tau in western blots on cases without neurofibrillary pathology is consistent with the hypothesis that the proteasome is capable of degrading normal tau with an intact projection domain at the amino - terminal end ; however , as proteasomal function [becomes] impaired [during] aging , tau clearance is impeded . 0 ###LEFT-WALL### 2 inability 0 ###LEFT-WALL### 14 is 0 ###LEFT-WALL### 36 - 0 ###LEFT-WALL### 54 . 1 the 2 inability 2 inability 3 to 2 inability 4 detect 2 inability 14 is 3 to 4 detect 4 detect 5 tau 5 tau 6 in 6 in 8 blots 7 western 8 blots 8 blots 9 on 9 on 10 cases 10 cases 11 without 11 without 13 pathology 12 neurofibrillary 13 pathology 14 is 15 consistent 15 consistent 16 with 15 consistent 33 at 16 with 18 hypothesis 16 with 25 degrading 17 the 18 hypothesis 18 hypothesis 19 that 18 hypothesis 24 of 19 that 21 proteasome 19 that 22 is 20 the 21 proteasome 21 proteasome 22 is 22 is 23 capable 23 capable 24 of 25 degrading 27 tau 26 normal 27 tau 27 tau 28 with 28 with 32 domain 29 an 30 intact 29 an 32 domain 30 intact 31 projection 31 projection 32 domain 33 at 35 amino 34 the 35 amino 36 - 38 end 36 - 39 ; 36 - 52 is 37 terminal 38 end 39 ; 51 clearance 40 however 41 , 40 however 51 clearance 42 as 48 aging 42 as 49 , 42 as 51 clearance 43 proteasomal 44 function 44 function 46 impaired 46 impaired 48 aging 50 tau 51 clearance 51 clearance 52 is 52 is 53 impeded tau accumulates in progressively larger and more heterogeneous forms in brains with neurofibrillary pathology . 0 ###LEFT-WALL### 1 tau 0 ###LEFT-WALL### 2 accumulates 0 ###LEFT-WALL### 15 . 1 tau 2 accumulates 2 accumulates 3 in 2 accumulates 10 in 2 accumulates 12 with 3 in 9 forms 4 progressively 5 larger 5 larger 6 and 6 and 7 more 6 and 9 forms 8 heterogeneous 9 forms 10 in 11 brains 12 with 14 pathology 13 neurofibrillary 14 pathology under normal conditions , [non] [-] proteasomal proteases are capable of digesting recombinant - tau from both the amino - and carboxyl - terminal ends toward the mid - section , [but] are lack of chaperon - like activity to unfold carboxyl - terminal truncated tau accumulated in ad . 1 under 3 conditions 1 under 4 , 1 under 8 proteases 2 normal 3 conditions 7 proteasomal 8 proteases 8 proteases 9 are 9 are 10 capable 10 capable 11 of 11 of 12 digesting 12 digesting 24 terminal 13 recombinant 15 tau 13 recombinant 23 - 13 recombinant 24 terminal 14 - 15 tau 15 tau 16 from 15 tau 23 - 16 from 21 and 17 both 21 and 18 the 19 amino 19 amino 21 and 20 - 21 and 21 and 22 carboxyl 21 and 23 - 24 terminal 25 ends 24 terminal 34 lack 24 terminal 35 of 25 ends 26 toward 25 ends 30 section 25 ends 33 are 26 toward 28 mid 27 the 28 mid 29 - 30 section 30 section 31 , 33 are 34 lack 35 of 36 chaperon 36 chaperon 38 like 36 chaperon 46 tau 37 - 38 like 38 like 39 activity 38 like 43 - 39 activity 40 to 39 activity 41 unfold 40 to 41 unfold 41 unfold 42 carboxyl 43 - 46 tau 44 terminal 46 tau 45 truncated 46 tau 46 tau 47 accumulated 46 tau 48 in 46 tau 50 . 48 in 49 ad our results support the hypothesis that failure of proteasomal [and] [non] - proteasomal proteolytic clearance mechanisms leads to tau accumulation and progressive neurofibrillary degeneration in ad . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 support 0 ###LEFT-WALL### 27 . 1 our 2 results 2 results 3 support 3 support 5 hypothesis 4 the 5 hypothesis 5 hypothesis 6 that 6 that 7 failure 6 that 17 leads 7 failure 8 of 7 failure 17 leads 8 of 16 mechanisms 9 proteasomal 12 - 9 proteasomal 16 mechanisms 13 proteasomal 16 mechanisms 14 proteolytic 16 mechanisms 15 clearance 16 mechanisms 17 leads 18 to 18 to 21 and 19 tau 20 accumulation 20 accumulation 21 and 21 and 24 degeneration 21 and 25 in 22 progressive 24 degeneration 23 neurofibrillary 24 degeneration 25 in 26 ad accelerated telomere length attrition has been associated with psychological stress and early adversity in adults ; however , no studies have examined whether telomere length in childhood is associated with early experiences . 0 ###LEFT-WALL### 4 attrition 0 ###LEFT-WALL### 7 associated 0 ###LEFT-WALL### 16 ; 0 ###LEFT-WALL### 22 examined 0 ###LEFT-WALL### 33 . 1 accelerated 2 telomere 2 telomere 4 attrition 3 length 4 attrition 4 attrition 5 has 5 has 6 been 6 been 7 associated 7 associated 8 with 7 associated 14 in 8 with 11 and 9 psychological 10 stress 10 stress 11 and 11 and 13 adversity 12 early 13 adversity 14 in 15 adults 16 ; 20 studies 17 however 18 , 17 however 20 studies 19 no 20 studies 20 studies 21 have 21 have 22 examined 22 examined 23 whether 22 examined 30 with 23 whether 25 length 23 whether 29 associated 24 telomere 25 length 25 length 26 in 25 length 28 is 26 in 27 childhood 28 is 29 associated 30 with 32 experiences 31 early 32 experiences the bucharest early intervention project is a unique randomized controlled trial of foster care placement compared with continued care in institutions . 0 ###LEFT-WALL### 5 project 0 ###LEFT-WALL### 6 is 0 ###LEFT-WALL### 22 . 1 the 5 project 2 bucharest 3 early 3 early 4 intervention 4 intervention 5 project 5 project 6 is 6 is 11 trial 7 a 11 trial 8 unique 11 trial 9 randomized 11 trial 10 controlled 11 trial 11 trial 12 of 12 of 15 placement 13 foster 14 care 14 care 15 placement 15 placement 16 compared 16 compared 17 with 16 compared 20 in 17 with 19 care 18 continued 19 care 20 in 21 institutions a significant negative correlation between t/s [ratio] and percentage of time was observed . 0 ###LEFT-WALL### 4 correlation 0 ###LEFT-WALL### 13 observed 0 ###LEFT-WALL### 14 . 1 a 2 significant 1 a 4 correlation 2 significant 4 correlation 3 negative 4 correlation 4 correlation 5 between 4 correlation 12 was 5 between 8 and 6 t/s 8 and 8 and 9 percentage 8 and 10 of 10 of 11 time 12 was 13 observed children with greater exposure to institutional care had significantly shorter relative telomere length in middle childhood . 0 ###LEFT-WALL### 1 children 0 ###LEFT-WALL### 8 had 0 ###LEFT-WALL### 17 . 1 children 2 with 1 children 8 had 2 with 4 exposure 3 greater 4 exposure 4 exposure 5 to 5 to 7 care 6 institutional 7 care 8 had 13 length 8 had 14 in 9 significantly 10 shorter 10 shorter 13 length 11 relative 13 length 12 telomere 13 length 14 in 16 childhood 15 middle 16 childhood gender modified this main effect . 0 ###LEFT-WALL### 1 gender 0 ###LEFT-WALL### 2 modified 0 ###LEFT-WALL### 6 . 1 gender 2 modified 2 modified 5 effect 3 this 5 effect 4 main 5 effect the percentage of time in institutional care at baseline significantly predicted telomere length in females , whereas the percentage of institutional care at 54 months was strongly predictive [of] telomere length in males . 0 ###LEFT-WALL### 2 percentage 0 ###LEFT-WALL### 26 was 0 ###LEFT-WALL### 34 . 1 the 2 percentage 2 percentage 3 of 2 percentage 11 predicted 3 of 4 time 4 time 5 in 4 time 8 at 5 in 7 care 6 institutional 7 care 8 at 9 baseline 10 significantly 11 predicted 11 predicted 13 length 11 predicted 14 in 11 predicted 17 whereas 12 telomere 13 length 14 in 15 females 16 , 17 whereas 17 whereas 19 percentage 18 the 19 percentage 19 percentage 20 of 19 percentage 26 was 20 of 22 care 21 institutional 22 care 22 care 23 at 23 at 25 months 24 54 25 months 26 was 31 length 27 strongly 28 predictive 28 predictive 31 length 30 telomere 31 length 31 length 32 in 32 in 33 males this is the first study to demonstrate an association between telomere length and institutionalization , the first study to find an association between adversity and telomere length in children , and contributes to the growing literature linking telomere length and early adversity . 0 ###LEFT-WALL### 1 this 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 43 . 1 this 2 is 2 is 5 study 3 the 5 study 4 first 5 study 5 study 6 to 5 study 7 demonstrate 6 to 7 demonstrate 7 demonstrate 9 association 7 demonstrate 19 to 8 an 9 association 9 association 10 between 9 association 17 first 9 association 18 study 10 between 13 and 11 telomere 12 length 12 length 13 and 13 and 14 institutionalization 13 and 15 , 16 the 17 first 17 first 18 study 19 to 31 and 20 find 22 association 20 find 23 between 20 find 27 length 20 find 28 in 20 find 31 and 21 an 22 association 23 between 25 and 24 adversity 25 and 25 and 26 telomere 28 in 29 children 30 , 31 and 31 and 32 contributes 31 and 33 to 33 to 40 and 34 the 36 literature 35 growing 36 literature 36 literature 37 linking 36 literature 40 and 37 linking 39 length 38 telomere 39 length 40 and 42 adversity 41 early 42 adversity background : research into nursing home transitions has given limited attention to the facility or community contexts . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 3 research 2 : 9 given 2 : 18 . 3 research 4 into 3 research 8 has 4 into 5 nursing 5 nursing 7 transitions 6 home 7 transitions 8 has 9 given 9 given 11 attention 9 given 15 or 10 limited 11 attention 11 attention 12 to 12 to 14 facility 13 the 14 facility 15 or 17 contexts 16 community 17 contexts objective : to identify facility and market factors affecting transitions of nursing home residents back to the community . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 2 : 3 to 2 : 6 and 2 : 19 . 3 to 6 and 4 identify 5 facility 4 identify 6 and 6 and 7 market 7 market 8 factors 7 market 15 back 7 market 16 to 8 factors 9 affecting 9 affecting 10 transitions 10 transitions 11 of 11 of 14 residents 12 nursing 14 residents 13 home 14 residents 16 to 18 community 17 the 18 community research design : multilevel models were used to estimate effects of facility and market factors on facility - level community discharge rates after controlling for resident demographic , health , and functional conditions . 0 ###LEFT-WALL### 2 design 0 ###LEFT-WALL### 14 market 0 ###LEFT-WALL### 34 . 1 research 2 design 2 design 3 : 3 : 4 multilevel 4 multilevel 5 models 4 multilevel 14 market 5 models 13 and 6 were 7 used 6 were 13 and 7 used 8 to 8 to 9 estimate 9 estimate 10 effects 10 effects 11 of 11 of 12 facility 13 and 14 market 14 market 31 and 15 factors 16 on 15 factors 31 and 16 on 17 facility 17 facility 19 level 18 - 19 level 19 level 21 discharge 19 level 24 controlling 19 level 30 , 20 community 21 discharge 21 discharge 22 rates 22 rates 23 after 23 after 24 controlling 24 controlling 25 for 25 for 29 health 26 resident 29 health 27 demographic 28 , 27 demographic 29 health 30 , 31 and 31 and 33 conditions 32 functional 33 conditions facility discharge rates were adjusted using empirical bayes estimation . 0 ###LEFT-WALL### 3 rates 0 ###LEFT-WALL### 5 adjusted 0 ###LEFT-WALL### 10 . 1 facility 3 rates 2 discharge 3 rates 3 rates 4 were 4 were 5 adjusted 5 adjusted 6 using 6 using 9 estimation 7 empirical 8 bayes 8 bayes 9 estimation subjects : annual [cohort] of first - time admissions ( n=24,648 ) to 378 minnesota nursing facilities in 75 nursing home markets from july 2005 to june 2006 . 0 ###LEFT-WALL### 1 subjects 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 7 - 1 subjects 2 : 2 : 3 annual 3 annual 5 of 5 of 6 first 7 - 8 time 7 - 29 . 8 time 9 admissions 8 time 13 to 8 time 18 in 9 admissions 11 n=24,648 10 ( 11 n=24,648 11 n=24,648 12 ) 13 to 15 minnesota 14 378 15 minnesota 15 minnesota 16 nursing 16 nursing 17 facilities 18 in 19 75 19 75 20 nursing 20 nursing 22 markets 20 nursing 23 from 20 nursing 26 to 21 home 22 markets 23 from 24 july 24 july 25 2005 26 to 27 june 27 june 28 2006 measures : community discharge within 90 days of admission ; facility occupancy , payer mix , ownership , case - mix acuity , size , admissions from hospitals , nurse staffing level , and proportion of admissions preferring [or] having support to return to the community [;] and nursing market population size , average occupancy , market concentration , and availability of home and community - based services . 0 ###LEFT-WALL### 1 measures 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 10 ; 1 measures 2 : 2 : 4 discharge 2 : 5 within 3 community 4 discharge 5 within 7 days 6 90 7 days 7 days 8 of 8 of 9 admission 10 ; 12 occupancy 10 ; 13 , 11 facility 12 occupancy 13 , 15 mix 13 , 16 , 14 payer 15 mix 16 , 17 ownership 16 , 18 , 18 , 19 case 18 , 20 - 20 - 22 acuity 20 - 23 , 21 mix 22 acuity 23 , 34 and 24 size 25 , 25 , 26 admissions 25 , 29 , 26 admissions 27 from 27 from 28 hospitals 29 , 32 level 29 , 34 and 30 nurse 32 level 31 staffing 32 level 33 , 34 and 34 and 35 proportion 34 and 36 of 34 and 38 preferring 34 and 41 support 36 of 37 admissions 38 preferring 40 having 41 support 42 to 41 support 44 to 41 support 52 size 42 to 43 return 44 to 50 market 45 the 46 community 46 community 48 and 48 and 49 nursing 48 and 50 market 51 population 52 size 52 size 55 occupancy 52 size 60 and 53 , 55 occupancy 54 average 55 occupancy 55 occupancy 56 , 56 , 60 and 57 market 58 concentration 58 concentration 60 and 59 , 60 and 60 and 61 availability 60 and 69 . 61 availability 62 of 62 of 64 and 63 home 64 and 64 and 65 community 64 and 66 - 64 and 68 services 66 - 68 services 67 based 68 services 68 services 69 . results : rates of community discharge ( empirical bayes [residual] ) were [highest] in facilities with more residents preferring community discharge , more medicare days , higher nurse staffing levels , and higher occupancy . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 3 rates 2 : 12 were 3 rates 4 of 3 rates 9 bayes 3 rates 12 were 4 of 6 discharge 5 community 6 discharge 7 ( 9 bayes 8 empirical 9 bayes 9 bayes 11 ) 12 were 14 in 14 in 15 facilities 15 facilities 16 with 15 facilities 18 residents 15 facilities 28 nurse 16 with 17 more 18 residents 19 preferring 18 residents 28 nurse 19 preferring 21 discharge 19 preferring 27 higher 20 community 21 discharge 21 discharge 25 days 22 , 23 more 22 , 25 days 24 medicare 25 days 25 days 26 , 28 nurse 32 and 29 staffing 30 levels 30 levels 32 and 31 , 32 and 32 and 34 occupancy 32 and 35 . 33 higher 34 occupancy in addition , facilities had higher community discharge rates if they were located in markets with a greater ratio of home and community - based services recipients to nursing home residents and with larger populations . 0 ###LEFT-WALL### 4 facilities 0 ###LEFT-WALL### 5 had 1 in 2 addition 1 in 3 , 1 in 4 facilities 4 facilities 5 had 5 had 9 rates 5 had 10 if 5 had 16 with 6 higher 7 community 7 community 9 rates 8 discharge 9 rates 10 if 11 they 10 if 13 located 11 they 12 were 12 were 13 located 13 located 14 in 14 in 15 markets 16 with 22 and 17 a 19 ratio 18 greater 19 ratio 19 ratio 20 of 19 ratio 22 and 20 of 21 home 22 and 23 community 22 and 27 recipients 24 - 27 recipients 25 based 26 services 26 services 27 recipients 27 recipients 32 and 27 recipients 36 . 28 to 29 nursing 28 to 32 and 29 nursing 31 residents 30 home 31 residents 32 and 33 with 33 with 35 populations 34 larger 35 populations conclusions : state medicaid programs should undertake system [-] level interventions that encourage nursing facilities to reduce unused bed capacity , balance the mix of payers , invest in nurse staffing , and take other steps to promote community discharges . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 21 , 0 ###LEFT-WALL### 41 . 1 conclusions 2 : 2 : 3 state 3 state 5 programs 3 state 7 undertake 4 medicaid 5 programs 5 programs 6 should 6 should 7 undertake 7 undertake 11 interventions 7 undertake 16 to 8 system 10 level 10 level 11 interventions 11 interventions 12 that 11 interventions 13 encourage 12 that 13 encourage 13 encourage 15 facilities 14 nursing 15 facilities 16 to 21 , 17 reduce 20 capacity 17 reduce 21 , 18 unused 19 bed 19 bed 20 capacity 21 , 27 , 22 balance 24 mix 22 balance 27 , 23 the 24 mix 24 mix 25 of 25 of 26 payers 27 , 33 and 28 invest 29 in 28 invest 33 and 29 in 31 staffing 30 nurse 31 staffing 32 , 33 and 33 and 34 take 34 take 36 steps 34 take 37 to 35 other 36 steps 37 to 38 promote 38 promote 40 discharges 39 community 40 discharges in addition , states should increase home and community - based services , particularly in markets with low community discharge rates . 0 ###LEFT-WALL### 4 states 0 ###LEFT-WALL### 6 increase 0 ###LEFT-WALL### 22 . 1 in 2 addition 1 in 3 , 1 in 4 states 4 states 5 should 5 should 6 increase 6 increase 8 and 6 increase 14 particularly 6 increase 17 with 7 home 8 and 8 and 9 community 8 and 12 services 10 - 12 services 11 based 12 services 12 services 13 , 14 particularly 15 in 15 in 16 markets 17 with 21 rates 18 low 19 community 19 community 21 rates 20 discharge 21 rates loss of cognitive [function] and hypertension are two common conditions in the elderly and both significantly contribute to loss of personal independency . 0 ###LEFT-WALL### 1 loss 0 ###LEFT-WALL### 7 are 0 ###LEFT-WALL### 14 and 0 ###LEFT-WALL### 23 . 1 loss 2 of 1 loss 7 are 2 of 5 and 3 cognitive 5 and 5 and 6 hypertension 7 are 10 conditions 8 two 10 conditions 9 common 10 conditions 10 conditions 11 in 11 in 13 elderly 12 the 13 elderly 14 and 15 both 14 and 17 contribute 15 both 17 contribute 16 significantly 17 contribute 17 contribute 18 to 18 to 19 loss 19 loss 20 of 20 of 22 independency 21 personal 22 independency microvascular brain damage - the result of age - associated alteration in large arteries and the progressive [mismatch] of their cross - talk with small cerebral arteries - represents a potent risk factor for cognitive [decline] and [for] the onset of dementia in older individuals . 0 ###LEFT-WALL### 3 damage 0 ###LEFT-WALL### 10 associated 0 ###LEFT-WALL### 15 and 0 ###LEFT-WALL### 46 . 1 microvascular 2 brain 2 brain 3 damage 3 damage 6 result 3 damage 10 associated 4 - 6 result 5 the 6 result 6 result 7 of 6 result 9 - 7 of 8 age 10 associated 11 alteration 10 associated 12 in 12 in 14 arteries 13 large 14 arteries 15 and 17 progressive 15 and 29 represents 16 the 17 progressive 17 progressive 19 of 17 progressive 23 talk 17 progressive 29 represents 19 of 21 cross 20 their 21 cross 22 - 23 talk 23 talk 24 with 23 talk 28 - 24 with 27 arteries 25 small 27 arteries 26 cerebral 27 arteries 29 represents 33 factor 29 represents 34 for 29 represents 43 in 30 a 31 potent 30 a 33 factor 31 potent 33 factor 32 risk 33 factor 34 for 37 and 35 cognitive 37 and 37 and 40 onset 37 and 41 of 39 the 40 onset 41 of 42 dementia 43 in 45 individuals 44 older 45 individuals the present review discusses the complexity of factors linking large [artery] to microvascular brain disease and [to] cognitive decline and the evidence for possible clinical markers useful for prevention of this phenomenon . 0 ###LEFT-WALL### 3 review 0 ###LEFT-WALL### 4 discusses 0 ###LEFT-WALL### 33 . 1 the 3 review 2 present 3 review 3 review 4 discusses 4 discusses 6 complexity 4 discusses 12 to 4 discusses 23 for 5 the 6 complexity 6 complexity 7 of 6 complexity 9 linking 7 of 8 factors 9 linking 10 large 12 to 20 and 13 microvascular 15 disease 14 brain 15 disease 15 disease 16 and 16 and 19 decline 16 and 20 and 18 cognitive 19 decline 20 and 22 evidence 21 the 22 evidence 23 for 26 markers 24 possible 26 markers 25 clinical 26 markers 26 markers 27 useful 26 markers 30 of 27 useful 28 for 28 for 29 prevention 30 of 32 phenomenon 31 this 32 phenomenon the possibility of dementia prevention by cardiovascular risk factors control has not been demonstrated . 0 ###LEFT-WALL### 2 possibility 0 ###LEFT-WALL### 14 demonstrated 0 ###LEFT-WALL### 15 . 1 the 2 possibility 2 possibility 3 of 2 possibility 11 has 3 of 5 prevention 4 dementia 5 prevention 5 prevention 6 by 6 by 8 risk 7 cardiovascular 8 risk 8 risk 9 factors 8 risk 10 control 9 factors 10 control 11 has 12 not 11 has 13 been 13 been 14 demonstrated in the absence of research clinical trials specifically [and] primarily designed to demonstrate the antihypertensive treatment efficacy for reducing the risk of dementia , further evidence demonstrating that it is possible to limit the progression of microvascular brain damage is needed . 0 ###LEFT-WALL### 7 trials 0 ###LEFT-WALL### 11 designed 1 in 3 absence 1 in 7 trials 2 the 3 absence 3 absence 4 of 4 of 5 research 6 clinical 7 trials 7 trials 11 designed 8 specifically 11 designed 10 primarily 11 designed 11 designed 12 to 11 designed 17 efficacy 11 designed 18 for 12 to 13 demonstrate 13 demonstrate 15 antihypertensive 14 the 15 antihypertensive 16 treatment 17 efficacy 18 for 19 reducing 19 reducing 21 risk 20 the 21 risk 21 risk 22 of 21 risk 26 evidence 22 of 23 dementia 24 , 26 evidence 25 further 26 evidence 26 evidence 27 demonstrating 26 evidence 31 possible 26 evidence 42 . 27 demonstrating 28 that 28 that 29 it 28 that 30 is 29 it 30 is 31 possible 32 to 31 possible 33 limit 32 to 33 limit 33 limit 35 progression 34 the 35 progression 35 progression 36 of 35 progression 41 needed 36 of 38 brain 37 microvascular 38 brain 38 brain 39 damage 38 brain 40 is 39 damage 40 is alzheimer disease is the most common cause of dementia . 0 ###LEFT-WALL### 2 disease 0 ###LEFT-WALL### 3 is 0 ###LEFT-WALL### 10 . 1 alzheimer 2 disease 2 disease 3 is 3 is 5 most 3 is 6 common 4 the 5 most 6 common 7 cause 7 cause 8 of 8 of 9 dementia it occurs worldwide and affects all ethnic groups . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 9 . 1 it 4 and 2 occurs 3 worldwide 2 occurs 4 and 4 and 5 affects 4 and 8 groups 6 all 8 groups 7 ethnic 8 groups the incidence of alzheimer disease is increasing due [,] in part [,] to increased life expectancy and the aging baby boomer generation . 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 23 . 1 the 2 incidence 2 incidence 3 of 2 incidence 8 due 2 incidence 17 and 3 of 4 alzheimer 4 alzheimer 5 disease 4 alzheimer 7 increasing 5 disease 6 is 6 is 7 increasing 8 due 11 part 10 in 11 part 11 part 13 to 13 to 16 expectancy 14 increased 15 life 15 life 16 expectancy 17 and 22 generation 18 the 22 generation 19 aging 22 generation 20 baby 22 generation 21 boomer 22 generation the average lifetime risk of developing alzheimer disease is 10 - 12 % . 0 ###LEFT-WALL### 4 risk 0 ###LEFT-WALL### 9 is 0 ###LEFT-WALL### 14 . 1 the 4 risk 2 average 3 lifetime 3 lifetime 4 risk 4 risk 5 of 4 risk 9 is 5 of 6 developing 6 developing 8 disease 7 alzheimer 8 disease 9 is 13 % 10 10 11 - 11 - 12 12 11 - 13 % this risk at least doubles with the presence of a first [-] degree relative with the disorder . 0 ###LEFT-WALL### 2 risk 0 ###LEFT-WALL### 5 doubles 0 ###LEFT-WALL### 18 . 1 this 2 risk 2 risk 5 doubles 3 at 4 least 4 least 5 doubles 5 doubles 6 with 5 doubles 15 with 6 with 8 presence 7 the 8 presence 8 presence 9 of 9 of 14 relative 10 a 14 relative 11 first 13 degree 13 degree 14 relative 15 with 17 disorder 16 the 17 disorder despite its limited utility , patients express concern over their risk and [,] in some instances , request testing . 0 ###LEFT-WALL### 6 patients 0 ###LEFT-WALL### 17 , 0 ###LEFT-WALL### 20 . 1 despite 4 utility 1 despite 5 , 1 despite 6 patients 2 its 4 utility 3 limited 4 utility 6 patients 17 , 7 express 8 concern 7 express 17 , 8 concern 12 and 9 over 11 risk 9 over 12 and 10 their 11 risk 12 and 14 in 14 in 16 instances 15 some 16 instances 17 , 18 request 18 request 19 testing furthermore , research has demonstrated that testing individuals for apolipoprotein e can be valuable and safe in certain contexts . 0 ###LEFT-WALL### 3 research 0 ###LEFT-WALL### 5 demonstrated 0 ###LEFT-WALL### 20 . 1 furthermore 2 , 1 furthermore 3 research 3 research 4 has 4 has 5 demonstrated 5 demonstrated 6 that 6 that 7 testing 6 that 13 be 7 testing 8 individuals 7 testing 12 can 8 individuals 9 for 9 for 10 apolipoprotein 10 apolipoprotein 11 e 12 can 13 be 13 be 15 and 14 valuable 15 and 15 and 16 safe 16 safe 17 in 17 in 19 contexts 18 certain 19 contexts however , because of the complicated genetic nature of the disorder , few clinicians are prepared to address the genetic risks of alzheimer disease with their patients . 0 ###LEFT-WALL### 14 clinicians 0 ###LEFT-WALL### 15 are 0 ###LEFT-WALL### 28 . 1 however 2 , 1 however 14 clinicians 2 , 3 because 3 because 4 of 3 because 12 , 3 because 14 clinicians 4 of 8 nature 5 the 8 nature 6 complicated 8 nature 7 genetic 8 nature 8 nature 9 of 9 of 11 disorder 10 the 11 disorder 13 few 14 clinicians 14 clinicians 15 are 15 are 16 prepared 16 prepared 17 to 16 prepared 18 address 17 to 18 address 18 address 21 risks 18 address 25 with 19 the 21 risks 20 genetic 21 risks 21 risks 22 of 22 of 24 disease 23 alzheimer 24 disease 25 with 27 patients 26 their 27 patients given the increased awareness in family history thanks to family history campaigns , the increasing incidence of alzheimer disease , and the availability of [direct] to consumer testing , patient requests for information is increasing . 0 ###LEFT-WALL### 16 incidence 0 ###LEFT-WALL### 34 is 0 ###LEFT-WALL### 36 . 1 given 4 awareness 1 given 9 to 1 given 13 , 1 given 16 incidence 2 the 4 awareness 3 increased 4 awareness 4 awareness 5 in 5 in 8 thanks 6 family 8 thanks 7 history 8 thanks 9 to 12 campaigns 10 family 11 history 11 history 12 campaigns 14 the 16 incidence 15 increasing 16 incidence 16 incidence 17 of 16 incidence 34 is 17 of 31 requests 18 alzheimer 19 disease 19 disease 21 and 20 , 21 and 21 and 23 availability 21 and 29 , 21 and 31 requests 22 the 23 availability 23 availability 24 of 24 of 26 to 26 to 28 testing 27 consumer 28 testing 30 patient 31 requests 31 requests 32 for 32 for 33 information 34 is 35 increasing this practice guideline provides clinicians with a framework for assessing their patients ' genetic risk for alzheimer disease , [identifying] which individuals may benefit from genetic testing , and providing the key elements of genetic counseling for ad . 0 ###LEFT-WALL### 3 guideline 0 ###LEFT-WALL### 4 provides 0 ###LEFT-WALL### 19 , 0 ###LEFT-WALL### 39 . 1 this 3 guideline 2 practice 3 guideline 3 guideline 4 provides 4 provides 5 clinicians 4 provides 6 with 6 with 8 framework 7 a 8 framework 8 framework 9 for 9 for 10 assessing 10 assessing 15 risk 11 their 12 patients 12 patients 13 ' 13 ' 15 risk 14 genetic 15 risk 15 risk 16 for 16 for 18 disease 17 alzheimer 18 disease 19 , 21 which 19 , 24 benefit 21 which 22 individuals 22 individuals 23 may 23 may 24 benefit 24 benefit 25 from 24 benefit 33 elements 24 benefit 37 for 25 from 29 and 26 genetic 27 testing 27 testing 29 and 28 , 29 and 29 and 30 providing 31 the 33 elements 32 key 33 elements 33 elements 34 of 34 of 36 counseling 35 genetic 36 counseling 37 for 38 ad natural [killer] ( nk ) cells are a key component of innate immunity involved not only in the elimination of virus [-] infected or tumor cells but also in the regulation of the immune response by producing cytokines and chemokines that can activate other cellular components of innate and adaptive immunity . 0 ###LEFT-WALL### 6 cells 0 ###LEFT-WALL### 7 are 0 ###LEFT-WALL### 15 not 0 ###LEFT-WALL### 52 . 1 natural 4 nk 1 natural 6 cells 3 ( 4 nk 4 nk 5 ) 6 cells 7 are 7 are 10 component 8 a 10 component 9 key 10 component 10 component 11 of 11 of 13 immunity 12 innate 13 immunity 13 immunity 14 involved 15 not 16 only 15 not 26 cells 15 not 43 activate 17 in 24 or 17 in 26 cells 18 the 19 elimination 19 elimination 20 of 19 elimination 23 infected 19 elimination 24 or 20 of 21 virus 24 or 25 tumor 26 cells 27 but 26 cells 29 in 26 cells 41 that 26 cells 42 can 26 cells 43 activate 27 but 28 also 29 in 39 and 30 the 31 regulation 31 regulation 32 of 31 regulation 36 by 31 regulation 39 and 32 of 35 response 33 the 35 response 34 immune 35 response 36 by 37 producing 37 producing 38 cytokines 39 and 40 chemokines 41 that 42 can 43 activate 46 components 44 other 46 components 45 cellular 46 components 46 components 47 of 47 of 51 immunity 48 innate 49 and 49 and 50 adaptive 49 and 51 immunity nk cell subsets are differentially affected by aging . 0 ###LEFT-WALL### 3 subsets 0 ###LEFT-WALL### 6 affected 0 ###LEFT-WALL### 9 . 1 nk 3 subsets 2 cell 3 subsets 3 subsets 4 are 4 are 5 differentially 4 are 6 affected 6 affected 7 by 7 by 8 aging whereas cd56 ( bright ) cells are decreased in healthy elderly individuals , the cd56 [(] dim ) subset is expanded . 0 ###LEFT-WALL### 6 cells 0 ###LEFT-WALL### 8 decreased 0 ###LEFT-WALL### 13 , 0 ###LEFT-WALL### 22 . 1 whereas 2 cd56 1 whereas 6 cells 3 ( 4 bright 4 bright 5 ) 4 bright 6 cells 6 cells 7 are 7 are 8 decreased 8 decreased 9 in 9 in 12 individuals 10 healthy 12 individuals 11 elderly 12 individuals 13 , 19 subset 13 , 21 expanded 14 the 19 subset 15 cd56 19 subset 17 dim 18 ) 17 dim 19 subset 19 subset 20 is 20 is 21 expanded the expression of cd57 , a marker of highly differentiated nk cells , is increased in the elderly ; this supports the notion that a remodeling process of nk cell subsets occurs in aging with a gradual decrease in more immature cd56 ( bright ) nk cells and an increase in highly differentiated cd56 ( dim ) cd57+ nk cells . 0 ###LEFT-WALL### 2 expression 0 ###LEFT-WALL### 15 increased 0 ###LEFT-WALL### 19 ; 1 the 2 expression 2 expression 3 of 2 expression 7 marker 2 expression 14 is 3 of 4 cd57 5 , 7 marker 6 a 7 marker 7 marker 8 of 7 marker 13 , 8 of 12 cells 9 highly 10 differentiated 10 differentiated 12 cells 11 nk 12 cells 14 is 15 increased 15 increased 16 in 16 in 18 elderly 17 the 18 elderly 19 ; 20 this 19 ; 21 supports 20 this 21 supports 21 supports 23 notion 21 supports 33 in 21 supports 35 with 22 the 23 notion 23 notion 24 that 24 that 27 process 24 that 32 occurs 25 a 27 process 26 remodeling 27 process 27 process 28 of 27 process 32 occurs 28 of 31 subsets 29 nk 30 cell 30 cell 31 subsets 33 in 34 aging 35 with 38 decrease 35 with 39 in 36 a 37 gradual 36 a 38 decrease 37 gradual 38 decrease 39 in 42 cd56 40 more 41 immature 41 immature 42 cd56 42 cd56 48 and 43 ( 48 and 44 bright 45 ) 44 bright 47 cells 46 nk 47 cells 47 cells 48 and 48 and 50 increase 48 and 51 in 48 and 60 cells 48 and 61 . 49 an 50 increase 51 in 54 cd56 52 highly 53 differentiated 53 differentiated 54 cd56 55 ( 60 cells 56 dim 57 ) 56 dim 58 cd57+ 58 cd57+ 60 cells 59 nk 60 cells 60 cells 61 . this nk cell redistribution can explain many of the phenotypic and functional changes in nk cells associated with healthy aging such as decreased proliferation [and] [the] maintenance of cd16 - dependent cytotoxicity . 0 ###LEFT-WALL### 4 redistribution 0 ###LEFT-WALL### 6 explain 1 this 4 redistribution 2 nk 4 redistribution 3 cell 4 redistribution 4 redistribution 5 can 5 can 6 explain 6 explain 13 changes 6 explain 14 in 6 explain 22 as 7 many 8 of 7 many 13 changes 8 of 13 changes 9 the 13 changes 10 phenotypic 11 and 11 and 12 functional 11 and 13 changes 14 in 16 cells 15 nk 16 cells 16 cells 17 associated 17 associated 18 with 18 with 20 aging 19 healthy 20 aging 21 such 22 as 22 as 27 maintenance 23 decreased 24 proliferation 24 proliferation 27 maintenance 27 maintenance 28 of 27 maintenance 32 cytotoxicity 28 of 29 cd16 30 - 32 cytotoxicity 31 dependent 32 cytotoxicity 32 cytotoxicity 33 . background : recent clinical studies have demonstrated that dimebon , a drug originally designed and used as a [non] [-] selective antihistamine , ameliorates symptoms and delays progress of mild to moderate forms of alzheimer 's and huntington 's diseases . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 23 , 0 ###LEFT-WALL### 41 . 1 background 2 : 2 : 3 recent 3 recent 5 studies 3 recent 7 demonstrated 3 recent 12 drug 4 clinical 5 studies 5 studies 6 have 6 have 7 demonstrated 7 demonstrated 9 dimebon 8 that 9 dimebon 10 , 12 drug 11 a 12 drug 12 drug 15 and 12 drug 23 , 13 originally 14 designed 14 designed 15 and 15 and 16 used 15 and 17 as 17 as 22 antihistamine 18 a 22 antihistamine 21 selective 22 antihistamine 23 , 26 and 24 ameliorates 25 symptoms 24 ameliorates 26 and 26 and 27 delays 27 delays 28 progress 28 progress 29 of 29 of 37 and 30 mild 31 to 30 mild 37 and 31 to 33 forms 32 moderate 33 forms 33 forms 34 of 34 of 36 's 35 alzheimer 36 's 37 and 40 diseases 38 huntington 39 's 39 's 40 diseases although the mechanism of dimebon action on pathological processes in degenerating brain is elusive , results of studies carried out in cell cultures and animal models suggested that this drug might affect the process of pathological accumulation and aggregation of various proteins involved in the pathogenesis of proteinopathies . 0 ###LEFT-WALL### 12 brain 0 ###LEFT-WALL### 13 is 0 ###LEFT-WALL### 24 and 0 ###LEFT-WALL### 49 . 1 although 3 mechanism 1 although 12 brain 2 the 3 mechanism 3 mechanism 4 of 4 of 6 action 5 dimebon 6 action 6 action 7 on 6 action 10 in 7 on 9 processes 8 pathological 9 processes 10 in 11 degenerating 12 brain 13 is 13 is 16 results 14 elusive 15 , 14 elusive 16 results 16 results 17 of 16 results 19 carried 17 of 18 studies 19 carried 20 out 19 carried 21 in 21 in 23 cultures 22 cell 23 cultures 24 and 26 models 24 and 27 suggested 25 animal 26 models 26 models 27 suggested 27 suggested 28 that 28 that 30 drug 28 that 32 affect 29 this 30 drug 30 drug 31 might 31 might 32 affect 32 affect 34 process 33 the 34 process 34 process 35 of 34 process 40 of 34 process 47 of 35 of 38 and 36 pathological 37 accumulation 37 accumulation 38 and 38 and 39 aggregation 40 of 42 proteins 41 various 42 proteins 42 proteins 43 involved 42 proteins 44 in 44 in 46 pathogenesis 45 the 46 pathogenesis 47 of 48 proteinopathies however , the effect of this drug on the pathology caused by overexpression and aggregation of alpha - synuclein , including parkinson 's disease ( pd ) , has not been assessed . 0 ###LEFT-WALL### 4 effect 0 ###LEFT-WALL### 31 been 0 ###LEFT-WALL### 33 . 1 however 2 , 1 however 4 effect 3 the 4 effect 4 effect 5 of 4 effect 29 has 5 of 14 and 6 this 7 drug 7 drug 8 on 7 drug 11 caused 7 drug 14 and 8 on 10 pathology 9 the 10 pathology 11 caused 12 by 12 by 13 overexpression 14 and 15 aggregation 14 and 16 of 14 and 19 synuclein 16 of 17 alpha 18 - 19 synuclein 19 synuclein 21 including 19 synuclein 28 , 20 , 21 including 21 including 24 disease 21 including 28 , 22 parkinson 23 's 23 's 24 disease 24 disease 26 pd 25 ( 26 pd 26 pd 27 ) 29 has 30 not 29 has 31 been 31 been 32 assessed objective : to test if dimebon affected alpha - synuclein - induced pathology using a transgenic animal model . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 2 : 3 to 2 : 4 test 2 : 19 . 3 to 4 test 4 test 5 if 5 if 8 alpha 5 if 12 induced 6 dimebon 7 affected 7 affected 8 alpha 8 alpha 10 synuclein 8 alpha 12 induced 9 - 10 synuclein 10 synuclein 11 - 12 induced 13 pathology 13 pathology 14 using 14 using 18 model 15 a 16 transgenic 15 a 18 model 16 transgenic 17 animal 17 animal 18 model methods : we studied the effects of chronic dimebon treatment on transgenic mice expressing [the] [c] - terminally truncated ( 1 - 120 [ )(form of human alpha - synuclein in dopaminergic neurons , a mouse model that recapitulates several biochemical , histopathological and behavioral characteristics of the early stage of pd . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 4 studied 2 : 3 we 3 we 4 studied 4 studied 6 effects 4 studied 11 on 5 the 6 effects 6 effects 7 of 7 of 10 treatment 8 chronic 9 dimebon 9 dimebon 10 treatment 11 on 13 mice 12 transgenic 13 mice 13 mice 14 expressing 13 mice 19 truncated 17 - 19 truncated 18 terminally 19 truncated 19 truncated 29 - 20 ( 29 - 21 1 22 - 22 - 23 120 22 - 25 )(form 25 )(form 26 of 25 )(form 29 - 26 of 28 alpha 27 human 28 alpha 29 - 30 synuclein 30 synuclein 31 in 31 in 33 neurons 32 dopaminergic 33 neurons 33 neurons 37 model 33 neurons 44 and 34 , 37 model 35 a 37 model 36 mouse 37 model 37 model 38 that 37 model 39 recapitulates 37 model 42 , 38 that 39 recapitulates 39 recapitulates 41 biochemical 40 several 41 biochemical 42 , 44 and 43 histopathological 44 and 44 and 46 characteristics 44 and 51 of 44 and 53 . 45 behavioral 46 characteristics 46 characteristics 47 of 47 of 50 stage 48 the 50 stage 49 early 50 stage 51 of 52 pd results : dimebon did not improve balance and coordination of aging transgenic animals or increase the level of striatal dopamine , nor did it prevent accumulation of alpha - synuclein in cell bodies of dopaminergic neurons . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 25 prevent 2 : 3 dimebon 2 : 14 or 3 dimebon 4 did 4 did 5 not 4 did 14 or 6 improve 8 and 6 improve 14 or 7 balance 8 and 8 and 9 coordination 8 and 10 of 10 of 11 aging 11 aging 13 animals 12 transgenic 13 animals 14 or 15 increase 15 increase 17 level 15 increase 22 nor 16 the 17 level 17 level 18 of 18 of 20 dopamine 19 striatal 20 dopamine 21 , 22 nor 22 nor 23 did 23 did 24 it 23 did 25 prevent 25 prevent 26 accumulation 26 accumulation 27 of 27 of 28 alpha 28 alpha 30 synuclein 29 - 30 synuclein 30 synuclein 31 in 30 synuclein 37 . 31 in 33 bodies 32 cell 33 bodies 33 bodies 34 of 34 of 36 neurons 35 dopaminergic 36 neurons conclusion : our observations suggest that in the studied model of alpha - synucleinopathy [dimebon] has very limited effect on certain pathological alterations typical of pd and related diseases . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 30 . 2 : 4 observations 2 : 27 and 3 our 4 observations 4 observations 27 and 5 suggest 6 that 5 suggest 27 and 6 that 14 synucleinopathy 6 that 16 has 7 in 10 model 7 in 13 - 7 in 14 synucleinopathy 8 the 10 model 9 studied 10 model 10 model 11 of 11 of 12 alpha 14 synucleinopathy 16 has 16 has 19 effect 16 has 20 on 17 very 18 limited 18 limited 19 effect 20 on 23 alterations 21 certain 23 alterations 22 pathological 23 alterations 23 alterations 24 typical 24 typical 25 of 25 of 26 pd 27 and 28 related 27 and 29 diseases lung cancer remains the leading cause of cancer - related mortality in the united states . 0 ###LEFT-WALL### 2 cancer 0 ###LEFT-WALL### 3 remains 0 ###LEFT-WALL### 10 related 0 ###LEFT-WALL### 16 . 1 lung 2 cancer 2 cancer 3 remains 3 remains 6 cause 4 the 6 cause 5 leading 6 cause 6 cause 7 of 7 of 8 cancer 9 - 10 related 10 related 11 mortality 10 related 12 in 12 in 15 states 13 the 15 states 14 united 15 states almost half of all lung cancer occurs at age > 70 years . 0 ###LEFT-WALL### 2 half 0 ###LEFT-WALL### 9 age 0 ###LEFT-WALL### 13 . 1 almost 2 half 2 half 3 of 2 half 9 age 3 of 4 all 4 all 6 cancer 4 all 8 at 5 lung 6 cancer 6 cancer 7 occurs 7 occurs 8 at 9 age 12 years 10 > 11 70 11 70 12 years the majority of patients with lung cancer present [with] locally advanced or metastatic disease . 0 ###LEFT-WALL### 4 patients 0 ###LEFT-WALL### 8 present 0 ###LEFT-WALL### 15 . 1 the 2 majority 2 majority 3 of 2 majority 4 patients 3 of 4 patients 4 patients 5 with 4 patients 8 present 5 with 7 cancer 6 lung 7 cancer 8 present 10 locally 8 present 14 disease 11 advanced 12 or 12 or 13 metastatic 12 or 14 disease management of advanced lung cancer in the older patient is a commonly encountered clinical scenario . 0 ###LEFT-WALL### 1 management 0 ###LEFT-WALL### 10 is 0 ###LEFT-WALL### 16 . 1 management 2 of 1 management 10 is 2 of 5 cancer 3 advanced 4 lung 4 lung 5 cancer 5 cancer 6 in 6 in 9 patient 7 the 9 patient 8 older 9 patient 10 is 15 scenario 11 a 15 scenario 12 commonly 13 encountered 13 encountered 15 scenario 14 clinical 15 scenario there is a paucity of clinical data guiding the management of lung cancer in the elderly due to underrepresentation of the elderly in clinical trials . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 26 . 1 there 2 is 2 is 4 paucity 3 a 4 paucity 4 paucity 5 of 4 paucity 8 guiding 5 of 7 data 6 clinical 7 data 8 guiding 10 management 8 guiding 14 in 8 guiding 18 to 9 the 10 management 10 management 11 of 11 of 13 cancer 12 lung 13 cancer 14 in 16 elderly 15 the 16 elderly 17 due 18 to 18 to 19 underrepresentation 19 underrepresentation 20 of 19 underrepresentation 23 in 20 of 22 elderly 21 the 22 elderly 23 in 25 trials 24 clinical 25 trials the elderly have unique alterations in physiology that put them at a greater risk of toxicity from chemotherapy and biologic therapy . 0 ###LEFT-WALL### 2 elderly 0 ###LEFT-WALL### 3 have 0 ###LEFT-WALL### 22 . 1 the 2 elderly 2 elderly 3 have 3 have 5 alterations 3 have 6 in 4 unique 5 alterations 6 in 7 physiology 7 physiology 8 that 7 physiology 9 put 8 that 9 put 9 put 10 them 9 put 11 at 11 at 14 risk 12 a 14 risk 13 greater 14 risk 14 risk 15 of 15 of 19 and 16 toxicity 17 from 16 toxicity 19 and 17 from 18 chemotherapy 19 and 21 therapy 20 biologic 21 therapy comorbid conditions , common among the elderly , can further reduce tolerance to therapy . 0 ###LEFT-WALL### 2 conditions 0 ###LEFT-WALL### 11 reduce 0 ###LEFT-WALL### 15 . 1 comorbid 2 conditions 2 conditions 4 common 2 conditions 9 can 3 , 4 common 4 common 5 among 4 common 8 , 5 among 7 elderly 6 the 7 elderly 9 can 11 reduce 10 further 11 reduce 11 reduce 12 tolerance 11 reduce 13 to 13 to 14 therapy as a consequence , older patients have worse outcomes than younger patients . 0 ###LEFT-WALL### 6 patients 0 ###LEFT-WALL### 7 have 0 ###LEFT-WALL### 13 . 1 as 3 consequence 1 as 4 , 1 as 6 patients 2 a 3 consequence 5 older 6 patients 6 patients 7 have 7 have 9 outcomes 7 have 10 than 8 worse 9 outcomes 10 than 12 patients 11 younger 12 patients it is important to look beyond chronologic age to better risk [stratify] patients when making treatment decisions in older patients with lung cancer . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 24 . 1 it 2 is 2 is 3 important 3 important 4 to 3 important 9 to 3 important 11 risk 4 to 5 look 5 look 6 beyond 6 beyond 8 age 7 chronologic 8 age 9 to 11 risk 10 better 11 risk 11 risk 13 patients 11 risk 14 when 14 when 15 making 15 making 16 treatment 15 making 17 decisions 15 making 18 in 15 making 21 with 18 in 20 patients 19 older 20 patients 21 with 23 cancer 22 lung 23 cancer the basic principles of management , especially in the fit [elderly] , do not differ from those in younger patients . 0 ###LEFT-WALL### 3 principles 0 ###LEFT-WALL### 15 differ 0 ###LEFT-WALL### 21 . 1 the 3 principles 2 basic 3 principles 3 principles 4 of 3 principles 13 do 4 of 5 management 5 management 8 in 6 , 7 especially 6 , 8 in 8 in 10 fit 8 in 12 , 9 the 10 fit 13 do 14 not 13 do 15 differ 15 differ 16 from 15 differ 18 in 16 from 17 those 18 in 20 patients 19 younger 20 patients this article provides an overview of management of advanced [non] - small cell lung cancer . 0 ###LEFT-WALL### 2 article 0 ###LEFT-WALL### 3 provides 0 ###LEFT-WALL### 16 . 1 this 2 article 2 article 3 provides 3 provides 5 overview 4 an 5 overview 5 overview 6 of 6 of 7 management 7 management 8 of 8 of 15 cancer 9 advanced 11 - 9 advanced 13 cell 12 small 13 cell 13 cell 15 cancer 14 lung 15 cancer the magnitude of the problem and current treatment guidelines for lung cancer are reviewed with a focus on barriers specific to the elderly . 0 ###LEFT-WALL### 6 and 0 ###LEFT-WALL### 14 reviewed 0 ###LEFT-WALL### 24 . 1 the 2 magnitude 2 magnitude 3 of 2 magnitude 6 and 3 of 6 and 4 the 5 problem 5 problem 6 and 6 and 9 guidelines 6 and 10 for 6 and 13 are 7 current 9 guidelines 8 treatment 9 guidelines 10 for 12 cancer 11 lung 12 cancer 13 are 14 reviewed 14 reviewed 15 with 14 reviewed 18 on 15 with 17 focus 16 a 17 focus 18 on 19 barriers 19 barriers 20 specific 20 specific 21 to 21 to 23 elderly 22 the 23 elderly the available clinical trials that have specifically studied the elderly with lung cancer are summarized . 0 ###LEFT-WALL### 4 trials 0 ###LEFT-WALL### 15 summarized 0 ###LEFT-WALL### 16 . 1 the 4 trials 2 available 4 trials 3 clinical 4 trials 4 trials 5 that 4 trials 6 have 4 trials 14 are 5 that 6 have 6 have 8 studied 7 specifically 8 studied 8 studied 10 elderly 8 studied 11 with 9 the 10 elderly 11 with 13 cancer 12 lung 13 cancer 14 are 15 summarized the evolving role of palliative care is discussed , as well as the need for integrating geriatric assessment in the care of elderly patients with lung cancer . 0 ###LEFT-WALL### 3 role 0 ###LEFT-WALL### 8 discussed 1 the 3 role 2 evolving 3 role 3 role 4 of 3 role 7 is 4 of 6 care 5 palliative 6 care 7 is 8 discussed 8 discussed 12 as 9 , 12 as 10 as 11 well 11 well 12 as 12 as 14 need 12 as 28 . 13 the 14 need 14 need 15 for 15 for 16 integrating 16 integrating 18 assessment 16 integrating 19 in 16 integrating 25 with 17 geriatric 18 assessment 19 in 21 care 20 the 21 care 21 care 22 of 22 of 24 patients 23 elderly 24 patients 25 with 27 cancer 26 lung 27 cancer objective chronic kidney disease ( ckd ) is present in patients with nonalcoholic fatty liver disease ( nafld ) . 0 ###LEFT-WALL### 4 disease 0 ###LEFT-WALL### 8 is 0 ###LEFT-WALL### 20 . 1 objective 2 chronic 2 chronic 4 disease 3 kidney 4 disease 4 disease 6 ckd 4 disease 8 is 5 ( 6 ckd 6 ckd 7 ) 8 is 9 present 9 present 10 in 9 present 12 with 10 in 11 patients 12 with 16 disease 13 nonalcoholic 15 liver 14 fatty 15 liver 15 liver 16 disease 16 disease 18 nafld 17 ( 18 nafld 18 nafld 19 ) the aim of this retrospective study was to assess the cumulative development incidence and predictive factors for new onset [of] ckd in japanese patients with nafld . 0 ###LEFT-WALL### 2 aim 0 ###LEFT-WALL### 27 . 1 the 2 aim 2 aim 3 of 2 aim 7 was 3 of 6 study 4 this 6 study 5 retrospective 6 study 7 was 8 to 7 was 9 assess 8 to 9 assess 9 assess 14 and 9 assess 17 for 9 assess 22 in 10 the 13 incidence 11 cumulative 12 development 12 development 13 incidence 13 incidence 14 and 14 and 16 factors 15 predictive 16 factors 17 for 21 ckd 18 new 21 ckd 19 onset 21 ckd 22 in 24 patients 23 japanese 24 patients 24 patients 25 with 25 with 26 nafld methods a [total] of 5,561 nafld patients without ckd were enrolled . 0 ###LEFT-WALL### 7 patients 0 ###LEFT-WALL### 11 enrolled 0 ###LEFT-WALL### 12 . 1 methods 2 a 1 methods 4 of 1 methods 7 patients 4 of 6 nafld 5 5,561 6 nafld 7 patients 8 without 7 patients 10 were 8 without 9 ckd 10 were 11 enrolled ckd [was] defined as [either] an estimated glomerular filtration rate of < 60 ml/min/1.73 m ( 2 ) or dipstick proteinuria ( ≥+1 ) . 0 ###LEFT-WALL### 19 or 0 ###LEFT-WALL### 25 . 1 ckd 3 defined 1 ckd 19 or 3 defined 4 as 4 as 10 rate 6 an 10 rate 7 estimated 9 filtration 8 glomerular 9 filtration 9 filtration 10 rate 10 rate 11 of 10 rate 17 2 11 of 15 m 12 < 13 60 13 60 15 m 14 ml/min/1.73 15 m 16 ( 17 2 17 2 18 ) 19 or 21 proteinuria 19 or 23 ≥+1 20 dipstick 21 proteinuria 22 ( 23 ≥+1 23 ≥+1 24 ) a blood sample and a urine sample were taken for routine analyses during [follow] - up . 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 9 taken 0 ###LEFT-WALL### 17 . 1 a 2 blood 1 a 3 sample 2 blood 3 sample 3 sample 4 and 4 and 7 sample 4 and 8 were 5 a 7 sample 6 urine 7 sample 8 were 9 taken 9 taken 10 for 9 taken 13 during 10 for 12 analyses 11 routine 12 analyses 13 during 16 up 15 - 16 up the mean observation period was 5.5 years . 0 ###LEFT-WALL### 4 period 0 ###LEFT-WALL### 5 was 0 ###LEFT-WALL### 8 . 1 the 4 period 2 mean 3 observation 3 observation 4 period 4 period 5 was 5 was 7 years 6 5.5 7 years the primary goal is the new development of ckd . 0 ###LEFT-WALL### 3 goal 0 ###LEFT-WALL### 4 is 0 ###LEFT-WALL### 10 . 1 the 3 goal 2 primary 3 goal 3 goal 4 is 4 is 7 development 5 the 7 development 6 new 7 development 7 development 8 of 8 of 9 ckd independent factors associated with new development of ckd were analyzed by using the kaplan - meyer method and the cox proportional hazards model . 0 ###LEFT-WALL### 2 factors 0 ###LEFT-WALL### 10 analyzed 0 ###LEFT-WALL### 15 - 0 ###LEFT-WALL### 24 . 1 independent 2 factors 2 factors 3 associated 2 factors 4 with 2 factors 7 of 2 factors 9 were 4 with 6 development 5 new 6 development 7 of 8 ckd 9 were 10 analyzed 10 analyzed 11 by 11 by 12 using 12 using 14 kaplan 13 the 14 kaplan 15 - 18 and 16 meyer 17 method 17 method 18 and 18 and 20 cox 18 and 22 hazards 18 and 23 model 19 the 20 cox 21 proportional 22 hazards 22 hazards 23 model results of 5.561 nafld patients , 263 patients developed ckd . 0 ###LEFT-WALL### 5 patients 0 ###LEFT-WALL### 6 , 0 ###LEFT-WALL### 11 . 1 results 2 of 2 of 3 5.561 2 of 4 nafld 4 nafld 5 patients 6 , 8 patients 6 , 9 developed 7 263 8 patients 8 patients 9 developed 9 developed 10 ckd the cumulative development rate of ckd was 3.1 % at the 5th year and [12.2] [%] at the 10th year . 0 ###LEFT-WALL### 4 rate 0 ###LEFT-WALL### 7 was 0 ###LEFT-WALL### 21 . 1 the 4 rate 2 cumulative 3 development 3 development 4 rate 4 rate 5 of 4 rate 7 was 5 of 6 ckd 7 was 9 % 8 3.1 9 % 9 % 14 and 10 at 13 year 10 at 14 and 11 the 13 year 12 5th 13 year 14 and 17 at 17 at 20 year 18 the 20 year 19 10th 20 year conclusion our retrospective study indicates that the annual incidence of ckd in japanese patients with nafld is about 1.2 % . 0 ###LEFT-WALL### 4 study 0 ###LEFT-WALL### 5 indicates 0 ###LEFT-WALL### 21 . 1 conclusion 4 study 2 our 4 study 3 retrospective 4 study 4 study 5 indicates 5 indicates 6 that 6 that 9 incidence 6 that 17 is 7 the 9 incidence 8 annual 9 incidence 9 incidence 10 of 9 incidence 12 in 9 incidence 17 is 10 of 11 ckd 12 in 14 patients 13 japanese 14 patients 14 patients 15 with 15 with 16 nafld 17 is 18 about 18 about 20 % 19 1.2 20 % five factors of low egfr level , aging , type 2 diabetes , hypertension , and elevated gamma - glutamyltransferase , increases the risk of the development of ckd . 0 ###LEFT-WALL### 2 factors 0 ###LEFT-WALL### 6 level 0 ###LEFT-WALL### 7 , 0 ###LEFT-WALL### 30 . 1 five 2 factors 2 factors 3 of 2 factors 6 level 3 of 5 egfr 4 low 5 egfr 7 , 10 type 7 , 13 , 8 aging 9 , 8 aging 10 type 10 type 11 2 10 type 12 diabetes 13 , 14 hypertension 13 , 16 and 15 , 16 and 16 and 18 gamma 16 and 22 increases 17 elevated 18 gamma 18 gamma 20 glutamyltransferase 18 gamma 22 increases 19 - 20 glutamyltransferase 20 glutamyltransferase 21 , 22 increases 24 risk 23 the 24 risk 24 risk 25 of 24 risk 28 of 25 of 27 development 26 the 27 development 28 of 29 ckd c57bl/6j and 129s6/sv ( b6 [and] 129 ) mice differ dramatically in their susceptibility to developing diabetes in response to diet - or genetically induced insulin resistance . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 10 differ 0 ###LEFT-WALL### 28 . 1 c57bl/6j 2 and 2 and 9 mice 2 and 10 differ 3 129s6/sv 5 b6 3 129s6/sv 9 mice 4 ( 5 b6 5 b6 7 129 5 b6 8 ) 10 differ 11 dramatically 10 differ 12 in 12 in 14 susceptibility 13 their 14 susceptibility 14 susceptibility 15 to 14 susceptibility 20 to 14 susceptibility 23 or 15 to 16 developing 16 developing 17 diabetes 16 developing 19 response 18 in 19 response 20 to 23 or 21 diet 23 or 22 - 23 or 23 or 25 induced 23 or 27 resistance 24 genetically 25 induced 26 insulin 27 resistance a major locus contributing to this difference has been mapped to a region on mouse chromosome 14 that contains the gene encoding pkcδ . 0 ###LEFT-WALL### 3 locus 0 ###LEFT-WALL### 10 mapped 0 ###LEFT-WALL### 24 . 1 a 2 major 1 a 3 locus 2 major 3 locus 3 locus 4 contributing 3 locus 8 has 4 contributing 5 to 5 to 7 difference 6 this 7 difference 8 has 9 been 9 been 10 mapped 10 mapped 11 to 10 mapped 14 on 11 to 13 region 12 a 13 region 14 on 16 chromosome 15 mouse 16 chromosome 16 chromosome 17 14 16 chromosome 18 that 16 chromosome 19 contains 18 that 19 contains 19 contains 21 gene 20 the 21 gene 21 gene 22 encoding 22 encoding 23 pkcδ here , we found that pkcδ expression in liver was 2 - fold higher in b6 versus 129 mice from birth and [was] further increased in b6 but not 129 mice in response to a high - fat diet . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 found 0 ###LEFT-WALL### 12 - 1 here 2 , 1 here 3 we 3 we 4 found 4 found 5 that 5 that 7 expression 5 that 10 was 6 pkcδ 7 expression 7 expression 8 in 7 expression 10 was 8 in 9 liver 10 was 11 2 12 - 22 and 12 - 40 . 13 fold 14 higher 13 fold 15 in 13 fold 22 and 15 in 16 b6 16 b6 17 versus 16 b6 20 from 17 versus 19 mice 18 129 19 mice 20 from 21 birth 22 and 25 increased 24 further 25 increased 25 increased 26 in 25 increased 28 but 25 increased 31 mice 25 increased 34 to 26 in 27 b6 28 but 29 not 30 129 31 mice 32 in 33 response 33 response 34 to 34 to 39 diet 35 a 36 high 35 a 39 diet 36 high 37 - 36 high 38 fat 38 fat 39 diet prkcd gene expression was also elevated in obese humans and was positively correlated with fasting glucose and circulating triglycerides . 0 ###LEFT-WALL### 3 expression 0 ###LEFT-WALL### 10 and 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 20 . 1 prkcd 3 expression 2 gene 3 expression 3 expression 10 and 4 was 6 elevated 4 was 10 and 5 also 6 elevated 6 elevated 7 in 7 in 9 humans 8 obese 9 humans 10 and 11 was 10 and 16 glucose 11 was 13 correlated 12 positively 13 correlated 13 correlated 14 with 14 with 15 fasting 17 and 18 circulating 17 and 19 triglycerides 18 circulating 19 triglycerides mice with global or liver - specific inactivation of the prkcd gene displayed increased hepatic insulin signaling and reduced expression of gluconeogenic and lipogenic enzymes . 0 ###LEFT-WALL### 8 inactivation 0 ###LEFT-WALL### 18 and 0 ###LEFT-WALL### 26 . 1 mice 8 inactivation 2 with 4 or 2 with 8 inactivation 3 global 4 or 4 or 5 liver 4 or 6 - 7 specific 8 inactivation 8 inactivation 9 of 8 inactivation 18 and 9 of 12 gene 10 the 12 gene 11 prkcd 12 gene 12 gene 13 displayed 14 increased 16 insulin 14 increased 18 and 15 hepatic 16 insulin 16 insulin 17 signaling 18 and 19 reduced 19 reduced 20 expression 20 expression 21 of 21 of 25 enzymes 22 gluconeogenic 23 and 23 and 24 lipogenic 23 and 25 enzymes this resulted in increased insulin - induced suppression of hepatic gluconeogenesis , improved glucose tolerance , and reduced hepatosteatosis with aging . 0 ###LEFT-WALL### 1 this 0 ###LEFT-WALL### 2 resulted 0 ###LEFT-WALL### 22 . 1 this 2 resulted 2 resulted 3 in 2 resulted 20 with 3 in 17 and 4 increased 5 insulin 4 increased 17 and 5 insulin 8 suppression 6 - 8 suppression 7 induced 8 suppression 8 suppression 9 of 8 suppression 15 tolerance 8 suppression 16 , 9 of 11 gluconeogenesis 10 hepatic 11 gluconeogenesis 12 , 15 tolerance 13 improved 14 glucose 14 glucose 15 tolerance 15 tolerance 16 , 17 and 18 reduced 17 and 19 hepatosteatosis 20 with 21 aging conversely , mice with liver - specific overexpression of pkcδ developed hepatic insulin resistance characterized by decreased insulin signaling , enhanced lipogenic gene expression , and hepatosteatosis . 0 ###LEFT-WALL### 3 mice 0 ###LEFT-WALL### 21 enhanced 0 ###LEFT-WALL### 28 . 1 conversely 2 , 1 conversely 3 mice 3 mice 4 with 3 mice 21 enhanced 4 with 5 liver 5 liver 8 overexpression 6 - 8 overexpression 7 specific 8 overexpression 8 overexpression 9 of 8 overexpression 19 signaling 8 overexpression 20 , 9 of 10 pkcδ 10 pkcδ 11 developed 10 pkcδ 16 by 11 developed 15 characterized 12 hepatic 13 insulin 13 insulin 14 resistance 14 resistance 15 characterized 16 by 18 insulin 17 decreased 18 insulin 21 enhanced 26 and 22 lipogenic 23 gene 23 gene 24 expression 24 expression 26 and 25 , 26 and 26 and 27 hepatosteatosis therefore , changes in the expression and regulation of pkcδ between strains of mice and in obese humans play an important role in the genetic risk of hepatic insulin resistance , glucose intolerance , and hepatosteatosis ; and thus pkcδ may be a potential target in the treatment [of] metabolic syndrome . 0 ###LEFT-WALL### 3 changes 0 ###LEFT-WALL### 19 play 0 ###LEFT-WALL### 37 ; 0 ###LEFT-WALL### 52 . 1 therefore 2 , 1 therefore 3 changes 3 changes 4 in 3 changes 9 of 3 changes 19 play 4 in 7 and 5 the 6 expression 6 expression 7 and 7 and 8 regulation 9 of 10 pkcδ 10 pkcδ 15 and 11 between 12 strains 11 between 15 and 12 strains 13 of 13 of 14 mice 15 and 16 in 16 in 18 humans 17 obese 18 humans 19 play 22 role 19 play 23 in 20 an 21 important 20 an 22 role 21 important 22 role 23 in 26 risk 24 the 26 risk 25 genetic 26 risk 26 risk 27 of 26 risk 35 and 27 of 30 resistance 28 hepatic 29 insulin 29 insulin 30 resistance 31 , 35 and 32 glucose 33 intolerance 33 intolerance 35 and 34 , 35 and 35 and 36 hepatosteatosis 35 and 37 ; 37 ; 38 and 38 and 39 thus 38 and 40 pkcδ 38 and 42 be 40 pkcδ 41 may 41 may 42 be 42 be 45 target 43 a 44 potential 43 a 45 target 44 potential 45 target 45 target 46 in 46 in 51 syndrome 47 the 51 syndrome 48 treatment 51 syndrome 50 metabolic 51 syndrome [none] none none tissue plasminogen [activator] ( tpa ) is the only available treatment [for] acute stroke . 0 ###LEFT-WALL### 5 plasminogen 0 ###LEFT-WALL### 10 is 0 ###LEFT-WALL### 18 . 2 none 3 none 3 none 4 tissue 4 tissue 5 plasminogen 5 plasminogen 8 tpa 5 plasminogen 10 is 7 ( 8 tpa 8 tpa 9 ) 10 is 17 stroke 11 the 12 only 11 the 17 stroke 13 available 14 treatment 14 treatment 17 stroke 16 acute 17 stroke in addition to its vascular fibrinolytic action , tpa exerts various effects within the brain , ranging from synaptic plasticity to control of cell fate . 0 ###LEFT-WALL### 9 tpa 0 ###LEFT-WALL### 10 exerts 1 in 2 addition 1 in 8 , 1 in 9 tpa 2 addition 3 to 3 to 7 action 4 its 7 action 5 vascular 7 action 6 fibrinolytic 7 action 9 tpa 10 exerts 10 exerts 12 effects 10 exerts 13 within 11 various 12 effects 13 within 15 brain 14 the 15 brain 15 brain 17 ranging 16 , 17 ranging 17 ranging 18 from 17 ranging 21 to 17 ranging 26 . 18 from 20 plasticity 19 synaptic 20 plasticity 21 to 22 control 22 control 23 of 23 of 25 fate 24 cell 25 fate to date , the influence of tpa in the ischemic brain has only been investigated on neuronal , microglial , and endothelial fate . 0 ###LEFT-WALL### 1 to 0 ###LEFT-WALL### 2 date 0 ###LEFT-WALL### 3 , 0 ###LEFT-WALL### 24 . 1 to 2 date 3 , 5 influence 3 , 15 investigated 4 the 5 influence 5 influence 6 of 5 influence 12 has 6 of 7 tpa 7 tpa 8 in 8 in 11 brain 9 the 11 brain 10 ischemic 11 brain 12 has 14 been 13 only 14 been 14 been 15 investigated 15 investigated 16 on 16 on 23 fate 17 neuronal 18 , 18 , 19 microglial 18 , 21 and 20 , 21 and 21 and 22 endothelial 21 and 23 fate we addressed the mechanism of action of tpa on oligodendrocyte ( ol ) survival and on the extent of white matter lesions [in] stroke . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 addressed 0 ###LEFT-WALL### 25 . 1 we 2 addressed 2 addressed 4 mechanism 3 the 4 mechanism 4 mechanism 5 of 5 of 6 action 6 action 7 of 7 of 8 tpa 8 tpa 15 and 9 on 14 survival 9 on 15 and 10 oligodendrocyte 12 ol 10 oligodendrocyte 14 survival 11 ( 12 ol 12 ol 13 ) 15 and 16 on 16 on 18 extent 17 the 18 extent 18 extent 19 of 19 of 21 matter 20 white 21 matter 21 matter 22 lesions 21 matter 24 stroke 22 lesions 24 stroke we also investigated the impact of aging on these processes . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 investigated 0 ###LEFT-WALL### 11 . 1 we 3 investigated 2 also 3 investigated 3 investigated 5 impact 4 the 5 impact 5 impact 6 of 6 of 7 aging 7 aging 8 on 8 on 10 processes 9 these 10 processes we observed that , in parallel [to] reduced levels of tpa in ols , white matter gets more susceptible to ischemia in old mice . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 observed 0 ###LEFT-WALL### 25 . 1 we 2 observed 2 observed 3 that 3 that 16 matter 3 that 17 gets 4 , 5 in 5 in 9 levels 5 in 14 , 5 in 16 matter 6 parallel 8 reduced 8 reduced 9 levels 9 levels 10 of 10 of 11 tpa 11 tpa 12 in 12 in 13 ols 15 white 16 matter 16 matter 17 gets 17 gets 19 susceptible 18 more 19 susceptible 19 susceptible 20 to 20 to 21 ischemia 21 ischemia 22 in 22 in 24 mice 23 old 24 mice interestingly , tpa protects murine and human ols from apoptosis through an unexpected cytokine - like effect by the virtue of its epidermal growth factor - [like] domain . 0 ###LEFT-WALL### 3 tpa 0 ###LEFT-WALL### 4 protects 0 ###LEFT-WALL### 26 - 1 interestingly 2 , 1 interestingly 3 tpa 3 tpa 4 protects 4 protects 6 and 4 protects 11 through 5 murine 6 and 6 and 8 ols 6 and 9 from 7 human 8 ols 9 from 10 apoptosis 11 through 14 cytokine 12 an 13 unexpected 12 an 14 cytokine 13 unexpected 14 cytokine 14 cytokine 16 like 15 - 16 like 16 like 17 effect 16 like 26 - 17 effect 18 by 17 effect 21 of 18 by 20 virtue 19 the 20 virtue 21 of 25 factor 22 its 25 factor 23 epidermal 24 growth 24 growth 25 factor 26 - 28 domain 26 - 29 . when injected into aged animals , tpa , [although] toxic to the gray matter , rescues white matter from ischemia independently of its proteolytic activity . 0 ###LEFT-WALL### 7 tpa 0 ###LEFT-WALL### 16 rescues 0 ###LEFT-WALL### 26 . 1 when 2 injected 1 when 6 , 1 when 7 tpa 2 injected 3 into 3 into 5 animals 4 aged 5 animals 7 tpa 10 toxic 7 tpa 16 rescues 8 , 10 toxic 10 toxic 11 to 10 toxic 15 , 11 to 14 matter 12 the 14 matter 13 gray 14 matter 16 rescues 18 matter 16 rescues 21 independently 17 white 18 matter 18 matter 19 from 19 from 20 ischemia 21 independently 22 of 22 of 25 activity 23 its 25 activity 24 proteolytic 25 activity these studies reveal a novel mechanism of action of tpa and unveil ol as a target cell for cytokine effects of tpa in brain diseases . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 26 . 1 these 2 studies 2 studies 11 and 3 reveal 6 mechanism 3 reveal 11 and 4 a 5 novel 4 a 6 mechanism 5 novel 6 mechanism 6 mechanism 7 of 6 mechanism 9 of 7 of 8 action 9 of 10 tpa 11 and 12 unveil 11 and 14 as 11 and 23 in 11 and 25 diseases 12 unveil 13 ol 14 as 17 cell 15 a 17 cell 16 target 17 cell 17 cell 18 for 17 cell 21 of 18 for 20 effects 19 cytokine 20 effects 21 of 22 tpa 23 in 24 brain they show overall that tpa protects white matter from stroke [-] induced lesions , an effect which may contribute to the global benefit of tpa - based stroke treatment . 0 ###LEFT-WALL### 1 they 0 ###LEFT-WALL### 2 show 0 ###LEFT-WALL### 26 - 1 they 2 show 2 show 3 overall 2 show 4 that 4 that 5 tpa 4 that 6 protects 5 tpa 6 protects 6 protects 8 matter 6 protects 9 from 7 white 8 matter 9 from 13 lesions 10 stroke 12 induced 12 induced 13 lesions 13 lesions 16 effect 14 , 16 effect 15 an 16 effect 16 effect 17 which 16 effect 18 may 16 effect 26 - 17 which 18 may 18 may 19 contribute 19 contribute 20 to 20 to 23 benefit 21 the 23 benefit 22 global 23 benefit 23 benefit 24 of 24 of 25 tpa 26 - 29 treatment 26 - 30 . 27 based 28 stroke 28 stroke 29 treatment discovered in caenorhabditis elegans in 1993 , micrornas ( mirnas ) make up a novel class of tiny , ~21 - 24 nucleotide , [non] - coding rna species . 0 ###LEFT-WALL### 8 micrornas 0 ###LEFT-WALL### 12 make 0 ###LEFT-WALL### 30 . 1 discovered 2 in 1 discovered 5 in 1 discovered 7 , 1 discovered 8 micrornas 2 in 4 elegans 3 caenorhabditis 4 elegans 5 in 6 1993 8 micrornas 10 mirnas 8 micrornas 12 make 9 ( 10 mirnas 10 mirnas 11 ) 12 make 13 up 12 make 16 class 14 a 15 novel 14 a 16 class 15 novel 16 class 16 class 17 of 17 of 29 species 18 tiny 20 ~21 18 tiny 29 species 19 , 20 ~21 20 ~21 23 nucleotide 20 ~21 26 - 21 - 23 nucleotide 22 24 23 nucleotide 23 nucleotide 24 , 27 coding 29 species 28 rna 29 species since its identification as a key component of a broadly conserved mechanism that regulates gene expression post - transcriptionally , the mirna pathway has emerged as one of the most extensively investigated pathways of the past decade . 0 ###LEFT-WALL### 23 pathway 0 ###LEFT-WALL### 25 emerged 0 ###LEFT-WALL### 38 . 1 since 3 identification 1 since 23 pathway 2 its 3 identification 3 identification 4 as 4 as 7 component 5 a 7 component 6 key 7 component 7 component 8 of 8 of 12 mechanism 9 a 12 mechanism 10 broadly 11 conserved 11 conserved 12 mechanism 12 mechanism 13 that 12 mechanism 14 regulates 13 that 14 regulates 14 regulates 17 post 14 regulates 19 transcriptionally 15 gene 17 post 16 expression 17 post 18 - 19 transcriptionally 19 transcriptionally 20 , 21 the 23 pathway 22 mirna 23 pathway 23 pathway 24 has 24 has 25 emerged 25 emerged 26 as 26 as 27 one 27 one 28 of 28 of 33 pathways 29 the 30 most 30 most 31 extensively 31 extensively 32 investigated 32 investigated 33 pathways 33 pathways 34 of 34 of 37 decade 35 the 37 decade 36 past 37 decade because of their potential to regulate a large number of protein - encoding genes , mirnas have been implicated in numerous biological processes , including development , stem cell regulation and human diseases . 0 ###LEFT-WALL### 16 mirnas 0 ###LEFT-WALL### 19 implicated 0 ###LEFT-WALL### 27 , 0 ###LEFT-WALL### 34 . 1 because 2 of 1 because 12 - 1 because 16 mirnas 2 of 4 potential 3 their 4 potential 4 potential 5 to 4 potential 6 regulate 5 to 6 regulate 6 regulate 11 protein 7 a 9 number 8 large 9 number 9 number 10 of 9 number 11 protein 10 of 11 protein 12 - 13 encoding 13 encoding 14 genes 13 encoding 15 , 13 encoding 16 mirnas 16 mirnas 17 have 17 have 18 been 18 been 19 implicated 19 implicated 20 in 20 in 23 processes 21 numerous 23 processes 22 biological 23 processes 23 processes 25 including 24 , 25 including 25 including 26 development 25 including 27 , 27 , 31 and 28 stem 30 regulation 29 cell 30 regulation 30 regulation 31 and 31 and 33 diseases 32 human 33 diseases in this commentary , we focus on mirnas and their roles in mammalian stem cells . 0 ###LEFT-WALL### 5 we 0 ###LEFT-WALL### 6 focus 0 ###LEFT-WALL### 16 . 1 in 3 commentary 1 in 4 , 1 in 5 we 2 this 3 commentary 5 we 6 focus 6 focus 7 on 6 focus 12 in 7 on 9 and 8 mirnas 9 and 9 and 11 roles 10 their 11 roles 12 in 15 cells 13 mammalian 14 stem 14 stem 15 cells following an introduction to the mirna biogenesis pathway with an emphasis on its regulatory features , we then discuss what is currently known about the roles that mirnas [have] in the differentiation and maintenance of embryonic and somatic stem cells of diverse origins . 0 ###LEFT-WALL### 1 following 0 ###LEFT-WALL### 28 mirnas 0 ###LEFT-WALL### 44 . 1 following 3 introduction 1 following 4 to 1 following 21 is 2 an 3 introduction 4 to 8 pathway 5 the 8 pathway 6 mirna 7 biogenesis 7 biogenesis 8 pathway 8 pathway 9 with 9 with 11 emphasis 9 with 17 we 9 with 19 discuss 10 an 11 emphasis 12 on 15 features 12 on 16 , 12 on 17 we 13 its 15 features 14 regulatory 15 features 17 we 19 discuss 18 then 19 discuss 19 discuss 20 what 21 is 22 currently 21 is 23 known 23 known 24 about 24 about 26 roles 25 the 26 roles 26 roles 27 that 26 roles 28 mirnas 27 that 28 mirnas 28 mirnas 30 in 30 in 33 and 31 the 32 differentiation 32 differentiation 33 and 33 and 34 maintenance 33 and 35 of 35 of 40 cells 36 embryonic 37 and 37 and 38 somatic 37 and 40 cells 39 stem 40 cells 40 cells 41 of 41 of 43 origins 42 diverse 43 origins in particular , their roles in stem cell differentiation have been well documented . 0 ###LEFT-WALL### 5 roles 0 ###LEFT-WALL### 11 been 0 ###LEFT-WALL### 14 . 1 in 2 particular 2 particular 3 , 2 particular 5 roles 4 their 5 roles 5 roles 6 in 5 roles 10 have 6 in 9 differentiation 7 stem 9 differentiation 8 cell 9 differentiation 10 have 11 been 11 been 12 well 12 well 13 documented insights from these studies provide a paradigm for the function of mirnas in facilitating cellular transitions during differentiation . 0 ###LEFT-WALL### 1 insights 0 ###LEFT-WALL### 5 provide 0 ###LEFT-WALL### 19 . 1 insights 2 from 1 insights 5 provide 2 from 4 studies 3 these 4 studies 5 provide 7 paradigm 5 provide 8 for 5 provide 13 in 5 provide 17 during 6 a 7 paradigm 8 for 10 function 9 the 10 function 10 function 11 of 11 of 12 mirnas 13 in 14 facilitating 14 facilitating 16 transitions 15 cellular 16 transitions 17 during 18 differentiation by contrast , the roles [that] mirnas have in the maintenance of stem cells are less well understood . 0 ###LEFT-WALL### 5 roles 0 ###LEFT-WALL### 18 understood 0 ###LEFT-WALL### 19 . 1 by 2 contrast 1 by 3 , 1 by 5 roles 4 the 5 roles 5 roles 7 mirnas 5 roles 8 have 5 roles 15 are 7 mirnas 8 have 8 have 9 in 9 in 11 maintenance 10 the 11 maintenance 11 maintenance 12 of 12 of 14 cells 13 stem 14 cells 15 are 17 well 15 are 18 understood 16 less 17 well however , with recent advances , their role as a rheostat that fine - tunes stem cell self - renewal has begun to emerge . 0 ###LEFT-WALL### 20 renewal 0 ###LEFT-WALL### 22 begun 0 ###LEFT-WALL### 25 . 1 however 2 , 1 however 20 renewal 2 , 3 with 3 with 5 advances 3 with 19 - 3 with 20 renewal 4 recent 5 advances 5 advances 8 role 6 , 8 role 7 their 8 role 8 role 9 as 8 role 19 - 9 as 18 self 10 a 18 self 11 rheostat 18 self 12 that 13 fine 13 fine 14 - 13 fine 15 tunes 15 tunes 18 self 16 stem 18 self 17 cell 18 self 20 renewal 21 has 21 has 22 begun 22 begun 23 to 22 begun 24 emerge 23 to 24 emerge finally , we discuss future studies that will hopefully lead to a comprehensive understanding of the mirna pathway in stem cells . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 discuss 0 ###LEFT-WALL### 22 . 1 finally 2 , 1 finally 3 we 3 we 4 discuss 4 discuss 6 studies 4 discuss 11 to 4 discuss 19 in 5 future 6 studies 6 studies 7 that 6 studies 8 will 7 that 8 will 8 will 10 lead 9 hopefully 10 lead 11 to 14 understanding 12 a 13 comprehensive 12 a 14 understanding 13 comprehensive 14 understanding 14 understanding 15 of 15 of 18 pathway 16 the 18 pathway 17 mirna 18 pathway 19 in 21 cells 20 stem 21 cells mutations in the cngb3 gene account for >50 [%] of all known cases of achromatopsia . 0 ###LEFT-WALL### 1 mutations 0 ###LEFT-WALL### 6 account 0 ###LEFT-WALL### 16 . 1 mutations 2 in 1 mutations 6 account 2 in 5 gene 3 the 5 gene 4 cngb3 5 gene 6 account 7 for 7 for 8 >50 8 >50 10 of 10 of 13 cases 11 all 13 cases 12 known 13 cases 13 cases 14 of 14 of 15 achromatopsia [although] [of] early onset , its stationary character and the potential for rapid assessment of restoration of retinal function following therapy renders achromatopsia a very attractive candidate for gene therapy . 0 ###LEFT-WALL### 4 onset 0 ###LEFT-WALL### 5 , 0 ###LEFT-WALL### 31 . 3 early 4 onset 5 , 9 and 5 , 23 achromatopsia 6 its 8 character 7 stationary 8 character 8 character 9 and 9 and 11 potential 9 and 12 for 9 and 15 of 9 and 23 achromatopsia 10 the 11 potential 12 for 14 assessment 13 rapid 14 assessment 15 of 16 restoration 16 restoration 17 of 17 of 20 following 18 retinal 19 function 19 function 20 following 20 following 21 therapy 20 following 22 renders 21 therapy 22 renders 23 achromatopsia 27 candidate 24 a 25 very 24 a 27 candidate 25 very 26 attractive 26 attractive 27 candidate 27 candidate 28 for 28 for 30 therapy 29 gene 30 therapy here we tested the efficacy of an raav2/8 vector containing a human cone arrestin promoter and a human cngb3 cdna in cngb3 deficient mice . 0 ###LEFT-WALL### 2 we 0 ###LEFT-WALL### 3 tested 0 ###LEFT-WALL### 25 . 1 here 2 we 2 we 3 tested 3 tested 5 efficacy 3 tested 21 in 4 the 5 efficacy 5 efficacy 6 of 6 of 16 and 7 an 9 vector 8 raav2/8 9 vector 9 vector 10 containing 9 vector 16 and 10 containing 15 promoter 11 a 12 human 11 a 15 promoter 12 human 13 cone 13 cone 15 promoter 14 arrestin 15 promoter 16 and 20 cdna 17 a 20 cdna 18 human 20 cdna 19 cngb3 20 cdna 21 in 24 mice 22 cngb3 24 mice 23 deficient 24 mice following subretinal delivery of the vector , cngb3 was detected in both m - and s - cones and resulted in increased levels of cnga3 , increased cone density and survival , improved cone outer segment structure and normal subcellular compartmentalization of cone opsins . 0 ###LEFT-WALL### 8 cngb3 0 ###LEFT-WALL### 9 was 0 ###LEFT-WALL### 32 , 0 ###LEFT-WALL### 45 . 1 following 3 delivery 1 following 7 , 1 following 8 cngb3 2 subretinal 3 delivery 3 delivery 4 of 4 of 6 vector 5 the 6 vector 8 cngb3 9 was 9 was 19 and 10 detected 11 in 10 detected 18 cones 10 detected 19 and 11 in 15 and 12 both 15 and 13 m 15 and 14 - 15 and 15 and 16 s 15 and 17 - 19 and 20 resulted 19 and 21 in 21 in 30 and 22 increased 23 levels 23 levels 24 of 23 levels 26 , 24 of 25 cnga3 26 , 29 density 26 , 30 and 27 increased 28 cone 28 cone 29 density 30 and 31 survival 32 , 38 and 33 improved 34 cone 34 cone 37 structure 35 outer 36 segment 36 segment 37 structure 37 structure 38 and 38 and 41 compartmentalization 38 and 42 of 39 normal 41 compartmentalization 40 subcellular 41 compartmentalization 42 of 44 opsins 43 cone 44 opsins therapy also resulted in long - term improvement of retinal [function] , [with] restoration of cone erg amplitudes of up to 90 % of wild - [type] and a significant improvement in visual acuity . 0 ###LEFT-WALL### 1 therapy 0 ###LEFT-WALL### 3 resulted 0 ###LEFT-WALL### 35 . 1 therapy 3 resulted 2 also 3 resulted 3 resulted 4 in 3 resulted 32 in 4 in 8 improvement 5 long 6 - 5 long 7 term 7 term 8 improvement 8 improvement 9 of 8 improvement 15 of 9 of 14 restoration 10 retinal 12 , 10 retinal 14 restoration 15 of 18 amplitudes 16 cone 18 amplitudes 17 erg 18 amplitudes 18 amplitudes 19 of 19 of 23 % 20 up 21 to 21 to 22 90 22 90 23 % 23 % 24 of 24 of 28 and 25 wild 28 and 26 - 28 and 28 and 31 improvement 29 a 30 significant 29 a 31 improvement 30 significant 31 improvement 32 in 34 acuity 33 visual 34 acuity remarkably , successful restoration of cone function [was] observed even [when] treatment was initiated at 6 months of age ; however , restoration of normal visual acuity was only possible in younger animals ( e.g [.] 2 - 4 weeks old ) . 0 ###LEFT-WALL### 4 restoration 0 ###LEFT-WALL### 14 initiated 0 ###LEFT-WALL### 20 ; 0 ###LEFT-WALL### 43 . 1 remarkably 2 , 1 remarkably 4 restoration 3 successful 4 restoration 4 restoration 5 of 4 restoration 13 was 5 of 12 treatment 6 cone 7 function 7 function 9 observed 9 observed 12 treatment 10 even 12 treatment 13 was 14 initiated 14 initiated 15 at 15 at 17 months 16 6 17 months 17 months 18 of 18 of 19 age 20 ; 23 restoration 20 ; 28 was 21 however 22 , 21 however 23 restoration 23 restoration 24 of 23 restoration 28 was 24 of 27 acuity 25 normal 27 acuity 26 visual 27 acuity 28 was 29 only 28 was 30 possible 30 possible 31 in 31 in 33 animals 32 younger 33 animals 33 animals 35 e.g 34 ( 35 e.g 35 e.g 37 2 35 e.g 41 old 35 e.g 42 ) 38 - 41 old 39 4 40 weeks 40 weeks 41 old 41 old 42 ) this study [represents] achievement of the most substantial restoration [of] visual function reported to date in an animal model of achromatopsia using a human gene construct , which has the potential to be utilized in clinical trials . 0 ###LEFT-WALL### 4 achievement 0 ###LEFT-WALL### 13 reported 0 ###LEFT-WALL### 27 , 0 ###LEFT-WALL### 38 . 1 this 4 achievement 2 study 4 achievement 4 achievement 5 of 4 achievement 13 reported 5 of 12 function 6 the 12 function 7 most 8 substantial 8 substantial 9 restoration 9 restoration 12 function 11 visual 12 function 13 reported 15 date 13 reported 16 in 14 to 15 date 16 in 19 model 17 an 19 model 18 animal 19 model 19 model 20 of 20 of 21 achromatopsia 21 achromatopsia 22 using 22 using 26 construct 23 a 26 construct 24 human 26 construct 25 gene 26 construct 27 , 28 which 27 , 34 utilized 28 which 29 has 28 which 34 utilized 29 has 31 potential 29 has 34 utilized 30 the 31 potential 31 potential 32 to 31 potential 33 be 32 to 33 be 34 utilized 35 in 35 in 37 trials 36 clinical 37 trials background : delirium is a frequent neuropsychiatric syndrome affecting medical and surgical elderly patients . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 3 delirium 2 : 4 is 2 : 15 . 3 delirium 4 is 4 is 8 syndrome 5 a 6 frequent 5 a 8 syndrome 6 frequent 8 syndrome 7 neuropsychiatric 8 syndrome 8 syndrome 9 affecting 9 affecting 14 patients 10 medical 11 and 11 and 12 surgical 11 and 14 patients 13 elderly 14 patients cholinergic dysfunction has been implicated in delirium pathophysiology and plasmatic acetylcholinesterase ( ache ) and butyrylcholinesterase ( buche ) activities are suppressed in patients with delirium . 0 ###LEFT-WALL### 2 dysfunction 0 ###LEFT-WALL### 5 implicated 0 ###LEFT-WALL### 27 . 1 cholinergic 2 dysfunction 2 dysfunction 3 has 3 has 4 been 4 been 5 implicated 5 implicated 6 in 6 in 7 delirium 7 delirium 20 activities 7 delirium 21 are 7 delirium 22 suppressed 8 pathophysiology 9 and 9 and 11 acetylcholinesterase 9 and 13 ache 9 and 15 and 10 plasmatic 11 acetylcholinesterase 12 ( 13 ache 13 ache 14 ) 15 and 16 butyrylcholinesterase 15 and 18 buche 15 and 20 activities 17 ( 18 buche 18 buche 19 ) 20 activities 21 are 22 suppressed 23 in 22 suppressed 25 with 23 in 24 patients 25 with 26 delirium in this cohort study , we investigated whether these changes emerge during delirium or whether they are present before its onset . 0 ###LEFT-WALL### 6 we 0 ###LEFT-WALL### 7 investigated 0 ###LEFT-WALL### 22 . 1 in 4 study 1 in 5 , 1 in 6 we 2 this 4 study 3 cohort 4 study 6 we 7 investigated 7 investigated 8 whether 8 whether 10 changes 8 whether 11 emerge 9 these 10 changes 10 changes 11 emerge 11 emerge 12 during 12 during 14 or 13 delirium 14 or 14 or 15 whether 14 or 16 they 14 or 18 present 16 they 17 are 17 are 18 present 18 present 19 before 19 before 21 onset 20 its 21 onset methods : plasma activities of ache and buche were measured pre - and postoperatively [in] consecutive patients ≥60 years old undergoing elective total hip replacement surgery . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 27 . 2 : 7 and 2 : 10 measured 2 : 13 and 3 plasma 4 activities 4 activities 5 of 4 activities 7 and 5 of 6 ache 7 and 8 buche 7 and 9 were 9 were 10 measured 10 measured 11 pre 12 - 13 and 13 and 17 patients 13 and 18 ≥60 14 postoperatively 17 patients 16 consecutive 17 patients 17 patients 18 ≥60 18 ≥60 26 surgery 19 years 20 old 20 old 26 surgery 21 undergoing 23 total 22 elective 23 total 23 total 26 surgery 24 hip 26 surgery 25 replacement 26 surgery in addition to a comprehensive clinical and demographic baseline evaluation , venous blood samples were collected from each subject in the morning of hospital admission 's day and in the morning of the first postoperative day . 0 ###LEFT-WALL### 14 samples 0 ###LEFT-WALL### 15 were 0 ###LEFT-WALL### 37 . 1 in 2 addition 1 in 11 , 1 in 14 samples 2 addition 3 to 3 to 10 evaluation 4 a 10 evaluation 5 comprehensive 9 baseline 6 clinical 7 and 7 and 8 demographic 7 and 9 baseline 9 baseline 10 evaluation 12 venous 13 blood 13 blood 14 samples 14 samples 15 were 15 were 16 collected 16 collected 17 from 16 collected 28 and 17 from 19 subject 18 each 19 subject 20 in 22 morning 20 in 28 and 21 the 22 morning 22 morning 23 of 23 of 27 day 24 hospital 25 admission 25 admission 26 's 26 's 27 day 28 and 29 in 29 in 31 morning 30 the 31 morning 31 morning 32 of 32 of 36 day 33 the 34 first 33 the 36 day 35 postoperative 36 day delirium was screened daily with confusion assessment method ( confirmed with diagnostic and statistical manual of mental disorders ( dsm - iv ) - tr ) . 0 ###LEFT-WALL### 1 delirium 0 ###LEFT-WALL### 3 screened 0 ###LEFT-WALL### 27 . 1 delirium 2 was 2 was 3 screened 3 screened 4 daily 3 screened 5 with 5 with 8 method 6 confusion 8 method 7 assessment 8 method 8 method 10 confirmed 9 ( 10 confirmed 10 confirmed 11 with 10 confirmed 26 ) 11 with 13 and 12 diagnostic 13 and 13 and 15 manual 13 and 16 of 13 and 20 dsm 14 statistical 15 manual 16 of 18 disorders 17 mental 18 disorders 19 ( 20 dsm 20 dsm 22 iv 20 dsm 25 tr 20 dsm 26 ) 21 - 22 iv 22 iv 23 ) 24 - 25 tr 25 tr 26 ) results : preoperatively , plasma esterase activity was significantly lower in patients who developed delirium compared with the remaining subjects . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 21 . 2 : 7 activity 2 : 8 was 3 preoperatively 4 , 3 preoperatively 7 activity 5 plasma 7 activity 6 esterase 7 activity 7 activity 8 was 8 was 9 significantly 8 was 10 lower 10 lower 11 in 10 lower 17 with 11 in 12 patients 12 patients 13 who 12 patients 16 compared 13 who 15 delirium 13 who 16 compared 14 developed 15 delirium 15 delirium 16 compared 17 with 20 subjects 18 the 19 remaining 18 the 20 subjects following surgery buche activity was lower in the delirium group but this difference disappeared after controlling for preoperative values . 0 ###LEFT-WALL### 1 following 0 ###LEFT-WALL### 5 was 0 ###LEFT-WALL### 11 but 0 ###LEFT-WALL### 20 . 1 following 4 activity 1 following 5 was 2 surgery 4 activity 3 buche 4 activity 5 was 6 lower 6 lower 7 in 7 in 10 group 8 the 10 group 9 delirium 10 group 11 but 13 difference 11 but 14 disappeared 12 this 13 difference 13 difference 14 disappeared 14 disappeared 15 after 15 after 16 controlling 16 controlling 17 for 17 for 19 values 18 preoperative 19 values plasma cholinesterase activity correlated positively with calcium and haemoglobin and [negatively] with total bilirubin and international normalised ratio . 0 ###LEFT-WALL### 3 activity 0 ###LEFT-WALL### 4 correlated 0 ###LEFT-WALL### 19 . 1 plasma 3 activity 2 cholinesterase 3 activity 3 activity 4 correlated 4 correlated 5 positively 4 correlated 10 and 6 with 8 and 6 with 10 and 7 calcium 8 and 8 and 9 haemoglobin 10 and 12 with 12 with 15 and 13 total 14 bilirubin 14 bilirubin 15 and 15 and 18 ratio 16 international 17 normalised 17 normalised 18 ratio conclusion : plasma cholinesterase activity can be a useful candidate biomarker to identify subjects at greater risk of developing postoperative delirium . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 22 . 2 : 5 activity 2 : 7 be 3 plasma 5 activity 4 cholinesterase 5 activity 5 activity 6 can 6 can 7 be 7 be 10 candidate 8 a 10 candidate 9 useful 10 candidate 10 candidate 11 biomarker 10 candidate 19 developing 11 biomarker 12 to 11 biomarker 18 of 12 to 13 identify 13 identify 14 subjects 13 identify 15 at 15 at 17 risk 16 greater 17 risk 17 risk 18 of 19 developing 21 delirium 20 postoperative 21 delirium the majority of patients with major depressive disorder ( mdd ) suffer from significant executive dysfunctions . 0 ###LEFT-WALL### 4 patients 0 ###LEFT-WALL### 12 suffer 0 ###LEFT-WALL### 17 . 1 the 2 majority 2 majority 3 of 2 majority 4 patients 3 of 4 patients 4 patients 5 with 4 patients 12 suffer 5 with 10 mdd 6 major 7 depressive 7 depressive 8 disorder 8 disorder 10 mdd 9 ( 10 mdd 10 mdd 11 ) 12 suffer 13 from 13 from 16 dysfunctions 14 significant 16 dysfunctions 15 executive 16 dysfunctions to investigate the time course of executive functions during antidepressant treatment , repeated measures of executive functions are necessary . 0 ###LEFT-WALL### 17 functions 0 ###LEFT-WALL### 18 are 0 ###LEFT-WALL### 20 . 1 to 2 investigate 1 to 12 , 1 to 17 functions 2 investigate 5 course 2 investigate 9 during 3 the 5 course 4 time 5 course 5 course 6 of 6 of 8 functions 7 executive 8 functions 9 during 11 treatment 10 antidepressant 11 treatment 12 , 13 repeated 13 repeated 14 measures 13 repeated 17 functions 14 measures 15 of 15 of 16 executive 17 functions 18 are 18 are 19 necessary in order to avoid practice effects , the assessment of alternate forms is suggested . 0 ###LEFT-WALL### 9 assessment 0 ###LEFT-WALL### 14 suggested 0 ###LEFT-WALL### 15 . 1 in 2 order 1 in 7 , 1 in 9 assessment 2 order 3 to 2 order 4 avoid 3 to 4 avoid 4 avoid 6 effects 5 practice 6 effects 8 the 9 assessment 9 assessment 10 of 9 assessment 13 is 10 of 12 forms 11 alternate 12 forms 13 is 14 suggested the aim of this study was to compare the processing times of four alternate versions of the trail making test ( tmt ) a [and] [b] in patients with mdd . 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 this 5 study 6 was 7 to 6 was 8 compare 7 to 8 compare 8 compare 11 times 9 the 11 times 10 processing 11 times 11 times 12 of 11 times 16 of 12 of 15 versions 13 four 15 versions 14 alternate 15 versions 16 of 28 patients 17 the 28 patients 18 trail 19 making 19 making 20 test 20 test 22 tmt 21 ( 22 tmt 22 tmt 23 ) 22 tmt 28 patients 24 a 27 in 27 in 28 patients 28 patients 29 with 29 with 30 mdd fifty - five subjects with dsm - iv mdd were included in the study . 0 ###LEFT-WALL### 1 fifty 0 ###LEFT-WALL### 2 - 2 - 4 subjects 2 - 7 - 3 five 4 subjects 4 subjects 5 with 5 with 6 dsm 7 - 9 mdd 7 - 11 included 7 - 15 . 8 iv 9 mdd 9 mdd 10 were 10 were 11 included 11 included 12 in 12 in 14 study 13 the 14 study we analyzed mean processing times and retest reliability of the four versions of tmt a and b ..y mean processing times did not differ between the four tested versions of tmt a and [b] [.] retest reliability of tmt a and [b] was between 0.76 and 0.89 and between 0.86 and 0.94 , respectively . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 6 and 0 ###LEFT-WALL### 16 and 1 we 6 and 2 analyzed 5 times 2 analyzed 6 and 3 mean 5 times 4 processing 5 times 6 and 7 retest 7 retest 8 reliability 8 reliability 9 of 8 reliability 13 of 9 of 12 versions 10 the 11 four 11 four 12 versions 13 of 14 tmt 14 tmt 15 a 16 and 17 b 16 and 18 ..y 17 b 18 ..y 18 ..y 19 mean 19 mean 20 processing 19 mean 41 and 20 processing 21 times 20 processing 41 and 22 did 23 not 22 did 33 and 22 did 41 and 24 differ 25 between 24 differ 33 and 25 between 29 versions 26 the 29 versions 27 four 29 versions 28 tested 29 versions 29 versions 30 of 30 of 31 tmt 31 tmt 32 a 33 and 36 retest 36 retest 37 reliability 37 reliability 38 of 38 of 39 tmt 39 tmt 40 a 41 and 43 was 43 was 48 and 43 was 54 respectively 44 between 46 and 44 between 48 and 45 0.76 46 and 46 and 47 0.89 48 and 49 between 49 between 51 and 50 0.86 51 and 51 and 52 0.94 53 , 54 respectively 54 respectively 55 . because of their identical difficulty and high reliability , the herein described versions of the tmt a [and] [b] are suitable for sequential testing of executive functioning . 0 ###LEFT-WALL### 13 versions 0 ###LEFT-WALL### 20 are 0 ###LEFT-WALL### 28 . 1 because 2 of 2 of 6 and 2 of 9 , 2 of 13 versions 3 their 5 difficulty 4 identical 5 difficulty 5 difficulty 6 and 6 and 8 reliability 7 high 8 reliability 10 the 13 versions 11 herein 12 described 12 described 13 versions 13 versions 14 of 13 versions 20 are 14 of 16 tmt 15 the 16 tmt 16 tmt 17 a 20 are 21 suitable 21 suitable 22 for 22 for 24 testing 23 sequential 24 testing 24 testing 25 of 25 of 26 executive 26 executive 27 functioning although several studies have shown that dual - tasking ability is impaired in alzheimer 's disease ( ad ) , the stage at which [this] deficit manifests remains unclear . 0 ###LEFT-WALL### 22 stage 0 ###LEFT-WALL### 30 . 1 although 3 studies 1 although 5 shown 1 although 22 stage 2 several 3 studies 3 studies 4 have 4 have 5 shown 5 shown 10 ability 5 shown 12 impaired 6 that 10 ability 7 dual 8 - 7 dual 10 ability 9 tasking 10 ability 10 ability 11 is 11 is 12 impaired 13 in 16 disease 13 in 20 , 13 in 22 stage 14 alzheimer 15 's 15 's 16 disease 16 disease 18 ad 17 ( 18 ad 18 ad 19 ) 21 the 22 stage 22 stage 23 at 22 stage 28 remains 23 at 24 which 23 at 27 manifests 24 which 27 manifests 26 deficit 27 manifests 28 remains 29 unclear this study investigated if a new paper - and [-] pencil assessment of dual - tasking ability could distinguish between ad , mild cognitive impairment ( mci ) and normal ageing in a sample of 50 people with ad , 49 people with mci , and 50 healthy age - matched controls . 0 ###LEFT-WALL### 29 and 0 ###LEFT-WALL### 50 - 0 ###LEFT-WALL### 53 . 1 this 2 study 2 study 3 investigated 2 study 29 and 3 investigated 4 if 4 if 9 and 4 if 19 distinguish 5 a 6 new 5 a 7 paper 6 new 7 paper 7 paper 9 and 8 - 9 and 9 and 12 assessment 9 and 13 of 9 and 18 could 11 pencil 12 assessment 13 of 17 ability 14 dual 15 - 14 dual 17 ability 16 tasking 17 ability 18 could 19 distinguish 19 distinguish 20 between 20 between 21 ad 21 ad 25 impairment 22 , 25 impairment 23 mild 25 impairment 24 cognitive 25 impairment 25 impairment 27 mci 25 impairment 28 ) 26 ( 27 mci 27 mci 28 ) 29 and 31 ageing 30 normal 31 ageing 31 ageing 32 in 31 ageing 35 of 32 in 34 sample 33 a 34 sample 35 of 46 and 36 50 37 people 37 people 38 with 37 people 40 , 38 with 39 ad 40 , 42 people 40 , 46 and 41 49 42 people 42 people 43 with 43 with 44 mci 45 , 46 and 46 and 49 age 46 and 50 - 47 50 49 age 48 healthy 49 age 50 - 52 controls 51 matched 52 controls the ad group demonstrated a significant impairment [in] dual - task ability . 0 ###LEFT-WALL### 3 group 0 ###LEFT-WALL### 4 demonstrated 0 ###LEFT-WALL### 13 . 1 the 3 group 2 ad 3 group 3 group 4 demonstrated 4 demonstrated 12 ability 5 a 6 significant 5 a 12 ability 6 significant 7 impairment 7 impairment 12 ability 9 dual 10 - 9 dual 11 task 11 task 12 ability there was no effect of [either] mci or healthy ageing on dual - task performance , indicating that the dual - task impairment is specific to ad . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 was 1 there 2 was 2 was 10 ageing 3 no 10 ageing 4 effect 5 of 4 effect 8 or 5 of 7 mci 8 or 9 healthy 8 or 10 ageing 10 ageing 11 on 10 ageing 17 indicating 11 on 15 performance 12 dual 13 - 12 dual 14 task 14 task 15 performance 16 , 17 indicating 17 indicating 18 that 17 indicating 28 . 18 that 23 impairment 18 that 24 is 19 the 23 impairment 20 dual 21 - 20 dual 23 impairment 22 task 23 impairment 23 impairment 24 is 24 is 25 specific 25 specific 26 to 26 to 27 ad background : carriers of a premutation ( cgg repeat length 55 - 200 ) in the fragile [x] mental retardation ( fmr1 ) [gene] are at risk for primary ovarian insufficiency ( fxpoi ) . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 35 . 2 : 3 carriers 2 : 25 are 3 carriers 4 of 3 carriers 15 in 3 carriers 25 are 4 of 6 premutation 5 a 6 premutation 6 premutation 10 length 7 ( 10 length 8 cgg 10 length 9 repeat 10 length 10 length 12 - 10 length 14 ) 11 55 12 - 12 - 13 200 15 in 20 retardation 16 the 20 retardation 17 fragile 20 retardation 19 mental 20 retardation 20 retardation 22 fmr1 21 ( 22 fmr1 22 fmr1 23 ) 25 are 26 at 25 are 28 for 26 at 27 risk 28 for 31 insufficiency 29 primary 31 insufficiency 30 ovarian 31 insufficiency 31 insufficiency 33 fxpoi 32 ( 33 fxpoi 33 fxpoi 34 ) the anti - müllerian hormone ( amh ) level acts as a useful marker of ovarian follicle reserve and , thus , may serve to predict when this ovarian reserve becomes too low to [sustain] [ovarian] function . 0 ###LEFT-WALL### 5 hormone 0 ###LEFT-WALL### 19 and 0 ###LEFT-WALL### 38 . 1 the 5 hormone 2 anti 3 - 2 anti 5 hormone 4 müllerian 5 hormone 5 hormone 7 amh 5 hormone 19 and 6 ( 7 amh 7 amh 8 ) 9 level 10 acts 10 acts 11 as 10 acts 19 and 11 as 14 marker 12 a 14 marker 13 useful 14 marker 14 marker 15 of 15 of 18 reserve 16 ovarian 18 reserve 17 follicle 18 reserve 19 and 23 may 19 and 25 to 19 and 34 to 20 , 21 thus 21 thus 22 , 21 thus 23 may 23 may 24 serve 25 to 26 predict 26 predict 27 when 27 when 30 reserve 27 when 31 becomes 28 this 30 reserve 29 ovarian 30 reserve 30 reserve 31 becomes 31 becomes 33 low 32 too 33 low 34 to 37 function we investigated the [intra] [-] individual variation of amh levels over time for premutation carriers compared with [non] - carriers . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 investigated 0 ###LEFT-WALL### 19 - 1 we 2 investigated 2 investigated 7 variation 2 investigated 11 over 2 investigated 13 for 3 the 7 variation 6 individual 7 variation 7 variation 8 of 8 of 10 levels 9 amh 10 levels 11 over 12 time 13 for 14 premutation 14 premutation 15 carriers 14 premutation 17 with 15 carriers 16 compared 16 compared 17 with 19 - 20 carriers 19 - 21 . methods : we determined amh levels in blood samples from 240 women ascertained through fragile [x] families , of which 127 were premutation carriers and 113 were [non] - carriers . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 31 . 2 : 3 we 2 : 4 determined 2 : 13 ascertained 2 : 18 , 2 : 29 - 3 we 4 determined 4 determined 6 levels 4 determined 13 ascertained 5 amh 6 levels 6 levels 7 in 6 levels 10 from 6 levels 13 ascertained 7 in 9 samples 8 blood 9 samples 10 from 12 women 11 240 12 women 13 ascertained 14 through 14 through 17 families 15 fragile 17 families 18 , 21 127 18 , 22 were 18 , 25 and 19 of 20 which 19 of 21 127 21 127 22 were 22 were 24 carriers 23 premutation 24 carriers 25 and 26 113 25 and 27 were 26 113 27 were 29 - 30 carriers linear mixed models were used to assess the effect of age and premutation status on amh levels and to determine a modeled amh value . 0 ###LEFT-WALL### 3 models 0 ###LEFT-WALL### 5 used 0 ###LEFT-WALL### 25 . 1 linear 3 models 2 mixed 3 models 3 models 4 were 4 were 5 used 5 used 6 to 5 used 7 assess 6 to 7 assess 7 assess 12 and 7 assess 18 and 8 the 9 effect 9 effect 10 of 9 effect 12 and 10 of 11 age 12 and 14 status 12 and 15 on 12 and 18 and 13 premutation 14 status 15 on 16 amh 17 levels 18 and 18 and 19 to 18 and 24 value 19 to 20 determine 20 determine 23 amh 21 a 23 amh 22 modeled 23 amh the stability over time of the deviation of observed amh levels from modeled levels , referred to as standardized amh values , was assessed through correlation coefficients of 41 longitudinal samples . 0 ###LEFT-WALL### 2 stability 0 ###LEFT-WALL### 24 assessed 0 ###LEFT-WALL### 32 . 1 the 2 stability 2 stability 3 over 2 stability 5 of 2 stability 17 to 2 stability 23 was 3 over 4 time 5 of 7 deviation 6 the 7 deviation 7 deviation 8 of 8 of 11 levels 9 observed 11 levels 10 amh 11 levels 11 levels 12 from 12 from 14 levels 13 modeled 14 levels 15 , 17 to 16 referred 17 to 17 to 18 as 17 to 22 , 18 as 21 values 19 standardized 21 values 20 amh 21 values 23 was 24 assessed 24 assessed 25 through 25 through 27 coefficients 26 correlation 27 coefficients 27 coefficients 28 of 28 of 31 samples 29 41 31 samples 30 longitudinal 31 samples results : at all ages , premutation carriers exhibited lower amh levels . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 6 , 0 ###LEFT-WALL### 13 . 1 results 2 : 2 : 3 at 3 at 5 ages 4 all 5 ages 6 , 8 carriers 6 , 10 lower 7 premutation 8 carriers 8 carriers 9 exhibited 8 carriers 10 lower 10 lower 12 levels 11 amh 12 levels for all women , amh was found to decrease by 10 % per year . 0 ###LEFT-WALL### 5 amh 0 ###LEFT-WALL### 7 found 0 ###LEFT-WALL### 15 . 1 for 3 women 1 for 4 , 1 for 5 amh 2 all 3 women 5 amh 6 was 6 was 7 found 7 found 8 to 8 to 9 decrease 9 decrease 10 by 10 by 12 % 11 10 12 % 12 % 13 per 13 per 14 year the added effect of having a premutation decreased amh levels by 54 % . 0 ###LEFT-WALL### 3 effect 0 ###LEFT-WALL### 8 decreased 0 ###LEFT-WALL### 14 . 1 the 3 effect 2 added 3 effect 3 effect 4 of 3 effect 8 decreased 4 of 5 having 5 having 7 premutation 6 a 7 premutation 8 decreased 10 levels 8 decreased 11 by 9 amh 10 levels 11 by 13 % 12 54 13 % the deviation of an individual 's amh level from the modeled value showed a reasonable [intra] - individual correlation . 0 ###LEFT-WALL### 2 deviation 0 ###LEFT-WALL### 13 showed 0 ###LEFT-WALL### 20 . 1 the 2 deviation 2 deviation 3 of 2 deviation 13 showed 3 of 8 level 4 an 5 individual 5 individual 6 's 6 's 8 level 7 amh 8 level 8 level 9 from 9 from 12 value 10 the 12 value 11 modeled 12 value 13 showed 19 correlation 14 a 15 reasonable 14 a 19 correlation 15 reasonable 17 - 15 reasonable 19 correlation 18 individual 19 correlation the pearson correlation coefficient of two samples taken at different ages was 0.36 ( p = 0.05 ) for [non] [-] carriers [and] 0.69 ( p = 0.01 ) for carriers . 0 ###LEFT-WALL### 4 coefficient 0 ###LEFT-WALL### 12 was 0 ###LEFT-WALL### 32 . 1 the 4 coefficient 2 pearson 4 coefficient 3 correlation 4 coefficient 4 coefficient 5 of 4 coefficient 12 was 5 of 7 samples 6 two 7 samples 7 samples 8 taken 8 taken 9 at 9 at 11 ages 10 different 11 ages 12 was 13 0.36 12 was 19 for 12 was 30 for 13 0.36 16 = 14 ( 16 = 15 p 16 = 16 = 17 0.05 16 = 18 ) 19 for 22 carriers 22 carriers 27 = 24 0.69 27 = 25 ( 27 = 26 p 27 = 27 = 28 0.01 27 = 29 ) 30 for 31 carriers conclusions : we developed a unique standardized amh value , taking fmr1 premutation status and the subject 's age into account , which appears to be stable over time and may serve as a predictor for fxpoi after further longitudinal assessment . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 3 we 2 : 4 developed 3 we 4 developed 4 developed 9 value 5 a 9 value 6 unique 9 value 7 standardized 9 value 8 amh 9 value 9 value 11 taking 9 value 23 which 10 , 11 taking 11 taking 15 and 11 taking 21 account 11 taking 22 , 12 fmr1 14 status 13 premutation 14 status 14 status 15 and 15 and 19 age 16 the 17 subject 17 subject 18 's 18 's 19 age 20 into 21 account 22 , 23 which 23 which 24 appears 23 which 42 . 24 appears 25 to 25 to 30 and 26 be 27 stable 26 be 30 and 27 stable 28 over 28 over 29 time 30 and 31 may 31 may 32 serve 32 serve 33 as 32 serve 38 after 33 as 35 predictor 34 a 35 predictor 35 predictor 36 for 36 for 37 fxpoi 38 after 41 assessment 39 further 41 assessment 40 longitudinal 41 assessment purpose : benign prostatic hyperplasia and hypogonadism are common disorders in aging men . 0 ###LEFT-WALL### 1 purpose 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 6 and 0 ###LEFT-WALL### 14 . 1 purpose 2 : 2 : 5 hyperplasia 3 benign 5 hyperplasia 4 prostatic 5 hyperplasia 6 and 7 hypogonadism 6 and 8 are 7 hypogonadism 8 are 8 are 10 disorders 9 common 10 disorders 10 disorders 11 in 11 in 12 aging 12 aging 13 men there is concern that androgen replacement in older men may increase prostate size and symptoms of benign prostatic hyperplasia . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 20 . 1 there 2 is 2 is 3 concern 3 concern 4 that 4 that 6 replacement 4 that 11 increase 5 androgen 6 replacement 6 replacement 7 in 6 replacement 10 may 7 in 9 men 8 older 9 men 10 may 11 increase 11 increase 14 and 12 prostate 13 size 13 size 14 and 14 and 15 symptoms 14 and 16 of 16 of 19 hyperplasia 17 benign 19 hyperplasia 18 prostatic 19 hyperplasia we examined whether combining dutasteride , which inhibits testosterone to dihydrotestosterone conversion , with testosterone treatment in older hypogonadal men with benign prostatic hyperplasia reduces androgenic stimulation of the prostate compared to testosterone alone . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 examined 0 ###LEFT-WALL### 35 . 1 we 2 examined 2 examined 3 whether 3 whether 4 combining 3 whether 25 reduces 4 combining 5 dutasteride 4 combining 14 with 4 combining 17 in 4 combining 25 reduces 5 dutasteride 7 which 6 , 7 which 7 which 8 inhibits 7 which 13 , 8 inhibits 9 testosterone 9 testosterone 10 to 10 to 12 conversion 11 dihydrotestosterone 12 conversion 14 with 16 treatment 15 testosterone 16 treatment 17 in 20 men 18 older 20 men 19 hypogonadal 20 men 20 men 21 with 21 with 24 hyperplasia 22 benign 24 hyperplasia 23 prostatic 24 hyperplasia 25 reduces 27 stimulation 25 reduces 32 to 25 reduces 34 alone 26 androgenic 27 stimulation 27 stimulation 28 of 28 of 30 prostate 29 the 30 prostate 30 prostate 31 compared 32 to 33 testosterone subjects were randomized to daily transdermal 1 % t gel plus oral placebo [or] dutasteride for 6 months . 0 ###LEFT-WALL### 1 subjects 0 ###LEFT-WALL### 3 randomized 0 ###LEFT-WALL### 19 . 1 subjects 2 were 2 were 3 randomized 3 randomized 4 to 3 randomized 11 plus 4 to 10 gel 5 daily 10 gel 6 transdermal 10 gel 7 1 9 t 8 % 9 t 9 t 10 gel 11 plus 15 dutasteride 12 oral 15 dutasteride 13 placebo 15 dutasteride 15 dutasteride 16 for 16 for 18 months 17 6 18 months testosterone dosing was adjusted to a serum testosterone of 500 to 1,000 ng/dl . 0 ###LEFT-WALL### 2 dosing 0 ###LEFT-WALL### 4 adjusted 0 ###LEFT-WALL### 14 . 1 testosterone 2 dosing 2 dosing 3 was 3 was 4 adjusted 4 adjusted 5 to 5 to 8 testosterone 6 a 7 serum 6 a 8 testosterone 7 serum 8 testosterone 8 testosterone 9 of 9 of 13 ng/dl 10 500 11 to 11 to 12 1,000 11 to 13 ng/dl the primary outcomes were prostate volume measured by magnetic resonance imaging , serum prostate specific antigen and androgen levels . 0 ###LEFT-WALL### 3 outcomes 0 ###LEFT-WALL### 4 were 0 ###LEFT-WALL### 20 . 1 the 3 outcomes 2 primary 3 outcomes 3 outcomes 4 were 4 were 6 volume 5 prostate 6 volume 6 volume 7 measured 7 measured 8 by 8 by 17 and 9 magnetic 10 resonance 10 resonance 11 imaging 11 imaging 12 , 12 , 16 antigen 12 , 17 and 13 serum 16 antigen 14 prostate 16 antigen 15 specific 16 antigen 17 and 19 levels 18 androgen 19 levels results : a total of 46 subjects completed all procedures . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 4 total 2 : 8 completed 2 : 11 . 3 a 4 total 4 total 5 of 4 total 8 completed 5 of 7 subjects 6 46 7 subjects 8 completed 10 procedures 9 all 10 procedures serum testosterone increased similarly into the mid - normal range in both groups . 0 ###LEFT-WALL### 2 testosterone 0 ###LEFT-WALL### 3 increased 0 ###LEFT-WALL### 14 . 1 serum 2 testosterone 2 testosterone 3 increased 3 increased 4 similarly 3 increased 11 in 4 similarly 5 into 5 into 10 range 6 the 10 range 7 mid 8 - 7 mid 10 range 9 normal 10 range 11 in 13 groups 12 both 13 groups serum dihydrotestosterone increased in the testosterone only but decreased in the testosterone plus dutasteride group . 0 ###LEFT-WALL### 2 dihydrotestosterone 0 ###LEFT-WALL### 8 but 0 ###LEFT-WALL### 16 . 1 serum 2 dihydrotestosterone 2 dihydrotestosterone 8 but 3 increased 4 in 3 increased 7 only 3 increased 8 but 4 in 6 testosterone 5 the 6 testosterone 8 but 9 decreased 9 decreased 10 in 10 in 15 group 11 the 15 group 12 testosterone 15 group 13 plus 15 group 14 dutasteride 15 group prostate symptom scores improved in both groups . 0 ###LEFT-WALL### 3 scores 0 ###LEFT-WALL### 4 improved 0 ###LEFT-WALL### 8 . 1 prostate 3 scores 2 symptom 3 scores 3 scores 4 improved 4 improved 5 in 5 in 7 groups 6 both 7 groups conclusions : combined treatment with testosterone plus dutasteride reduces prostate volume and prostate specific antigen compared to testosterone only . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 4 treatment 2 : 9 reduces 2 : 12 and 2 : 18 testosterone 2 : 20 . 3 combined 4 treatment 4 treatment 5 with 4 treatment 9 reduces 5 with 8 dutasteride 6 testosterone 7 plus 7 plus 8 dutasteride 9 reduces 11 volume 10 prostate 11 volume 12 and 15 antigen 12 and 16 compared 13 prostate 15 antigen 14 specific 15 antigen 15 antigen 16 compared 16 compared 17 to 17 to 18 testosterone 18 testosterone 19 only coadministration of a 5α - reductase inhibitor with testosterone appears to spare the prostate from androgenic stimulation during testosterone replacement in older , hypogonadal men with symptomatic benign prostatic hyperplasia . 0 ###LEFT-WALL### 1 coadministration 0 ###LEFT-WALL### 10 appears 0 ###LEFT-WALL### 31 . 1 coadministration 2 of 1 coadministration 8 with 1 coadministration 10 appears 2 of 7 inhibitor 3 a 4 5α 3 a 7 inhibitor 4 5α 5 - 4 5α 6 reductase 6 reductase 7 inhibitor 8 with 9 testosterone 10 appears 11 to 10 appears 12 spare 11 to 12 spare 12 spare 14 prostate 12 spare 15 from 12 spare 18 during 12 spare 21 in 12 spare 26 with 13 the 14 prostate 15 from 17 stimulation 16 androgenic 17 stimulation 18 during 20 replacement 19 testosterone 20 replacement 21 in 25 men 22 older 23 , 22 older 25 men 24 hypogonadal 25 men 26 with 30 hyperplasia 27 symptomatic 30 hyperplasia 28 benign 30 hyperplasia 29 prostatic 30 hyperplasia sirtuin 1 ( sirt1 ) is a longevity gene that protects cells against oxidative and genotoxic stress . 0 ###LEFT-WALL### 1 sirtuin 0 ###LEFT-WALL### 6 is 0 ###LEFT-WALL### 18 . 1 sirtuin 2 1 1 sirtuin 4 sirt1 1 sirtuin 6 is 3 ( 4 sirt1 4 sirt1 5 ) 6 is 9 gene 7 a 9 gene 8 longevity 9 gene 9 gene 10 that 9 gene 11 protects 10 that 11 protects 11 protects 12 cells 11 protects 13 against 13 against 17 stress 14 oxidative 15 and 15 and 16 genotoxic 15 and 17 stress this study aimed to investigate the associations of sirt1 gene single nucleotide polymorphisms ( snps ) , rs7895833 , rs7069102 , and rs2273773 , with various laboratory data in 1279 japanese health checkup examinees . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 aimed 0 ###LEFT-WALL### 35 . 1 this 2 study 2 study 3 aimed 3 aimed 4 to 3 aimed 25 with 3 aimed 29 in 4 to 5 investigate 5 investigate 7 associations 6 the 7 associations 7 associations 8 of 7 associations 15 snps 7 associations 22 and 8 of 13 polymorphisms 9 sirt1 12 nucleotide 10 gene 12 nucleotide 11 single 12 nucleotide 12 nucleotide 13 polymorphisms 14 ( 15 snps 15 snps 16 ) 17 , 22 and 18 rs7895833 19 , 18 rs7895833 20 rs7069102 20 rs7069102 22 and 21 , 22 and 22 and 23 rs2273773 22 and 24 , 25 with 28 data 26 various 27 laboratory 27 laboratory 28 data 29 in 34 examinees 30 1279 34 examinees 31 japanese 32 health 32 health 33 checkup 33 checkup 34 examinees the genotyping was performed using a polymerase chain reaction ( pcr ) with confronting 2 - pair primers ( ctpp ) assay . 0 ###LEFT-WALL### 2 genotyping 0 ###LEFT-WALL### 4 performed 0 ###LEFT-WALL### 23 . 1 the 2 genotyping 2 genotyping 3 was 3 was 4 performed 4 performed 5 using 5 using 9 reaction 5 using 13 with 6 a 9 reaction 7 polymerase 9 reaction 8 chain 9 reaction 9 reaction 11 pcr 10 ( 11 pcr 11 pcr 12 ) 13 with 14 confronting 14 confronting 15 2 14 confronting 22 assay 15 2 18 primers 15 2 22 assay 16 - 18 primers 17 pair 18 primers 18 primers 20 ctpp 18 primers 21 ) 19 ( 20 ctpp 20 ctpp 21 ) concerning rs7895833 ( a allele frequency [:] 0.290 ) , body fat [ratio] and body mass index were high in the aa carriers of male subjects , and diastolic blood pressure was high in the aa carriers of female subjects . 0 ###LEFT-WALL### 14 and 0 ###LEFT-WALL### 18 were 0 ###LEFT-WALL### 28 and 0 ###LEFT-WALL### 41 . 1 concerning 2 rs7895833 1 concerning 10 , 1 concerning 14 and 2 rs7895833 6 frequency 3 ( 6 frequency 4 a 5 allele 4 a 6 frequency 5 allele 6 frequency 6 frequency 8 0.290 6 frequency 9 ) 11 body 12 fat 12 fat 14 and 14 and 17 index 14 and 18 were 15 body 17 index 16 mass 17 index 18 were 19 high 19 high 20 in 20 in 23 carriers 21 the 23 carriers 22 aa 23 carriers 23 carriers 24 of 24 of 26 subjects 25 male 26 subjects 27 , 28 and 28 and 31 pressure 28 and 32 was 29 diastolic 30 blood 30 blood 31 pressure 31 pressure 32 was 32 was 33 high 33 high 34 in 34 in 37 carriers 35 the 37 carriers 36 aa 37 carriers 37 carriers 38 of 38 of 40 subjects 39 female 40 subjects concerning rs7069102 ( [g] allele frequency [:] 0.181 ) , body fat ratio and systolic blood pressure were high in the gg carriers of male subjects . 0 ###LEFT-WALL### 13 ratio 0 ###LEFT-WALL### 14 and 0 ###LEFT-WALL### 27 . 1 concerning 13 ratio 2 rs7069102 6 frequency 2 rs7069102 10 , 2 rs7069102 11 body 3 ( 6 frequency 5 allele 6 frequency 6 frequency 8 0.181 6 frequency 9 ) 11 body 13 ratio 12 fat 13 ratio 14 and 17 pressure 14 and 18 were 15 systolic 16 blood 16 blood 17 pressure 17 pressure 18 were 18 were 19 high 19 high 20 in 20 in 23 carriers 21 the 23 carriers 22 gg 23 carriers 23 carriers 24 of 24 of 26 subjects 25 male 26 subjects concerning rs2273773 ( [c] allele frequency [:] 0.323 ) , fasting glucose and body fat ratio were high in the tt carriers of male subjects , and systolic and diastolic blood pressures were high in the [cc] carriers of male subjects . 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 17 were 0 ###LEFT-WALL### 29 and 0 ###LEFT-WALL### 42 . 1 concerning 2 rs2273773 1 concerning 10 , 1 concerning 13 and 2 rs2273773 6 frequency 3 ( 6 frequency 5 allele 6 frequency 6 frequency 8 0.323 6 frequency 9 ) 11 fasting 12 glucose 12 glucose 13 and 13 and 16 ratio 13 and 17 were 14 body 16 ratio 15 fat 16 ratio 17 were 18 high 18 high 19 in 19 in 27 and 20 the 22 carriers 21 tt 22 carriers 22 carriers 23 of 22 carriers 27 and 23 of 25 subjects 24 male 25 subjects 26 , 27 and 27 and 28 systolic 29 and 32 pressures 29 and 33 were 30 diastolic 31 blood 31 blood 32 pressures 32 pressures 33 were 33 were 34 high 34 high 35 in 35 in 38 carriers 36 the 38 carriers 38 carriers 39 of 39 of 41 subjects 40 male 41 subjects thus , the [a] allele of rs7895833 , [g] allele of rs7069102 , and t allele of rs2273773 carried a high risk for obesity in men . 0 ###LEFT-WALL### 5 allele 0 ###LEFT-WALL### 19 carried 0 ###LEFT-WALL### 27 . 1 thus 2 , 1 thus 5 allele 3 the 5 allele 5 allele 6 of 5 allele 11 of 5 allele 19 carried 6 of 10 allele 7 rs7895833 8 , 7 rs7895833 10 allele 11 of 16 allele 12 rs7069102 14 and 13 , 14 and 14 and 15 t 14 and 16 allele 16 allele 17 of 17 of 18 rs2273773 19 carried 22 risk 19 carried 25 in 20 a 21 high 20 a 22 risk 21 high 22 risk 22 risk 23 for 23 for 24 obesity 25 in 26 men furthermore , the [a] allele of rs7895833 in women , and the [g] allele of rs7069102 and [c] allele of rs2273773 in men , carried a high risk [for] hypertension . 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 25 carried 0 ###LEFT-WALL### 31 . 1 furthermore 2 , 1 furthermore 11 and 3 the 5 allele 5 allele 6 of 5 allele 11 and 6 of 7 rs7895833 7 rs7895833 8 in 8 in 9 women 10 , 11 and 11 and 14 allele 11 and 15 of 11 and 25 carried 12 the 14 allele 15 of 17 and 16 rs7069102 17 and 17 and 19 allele 17 and 24 , 19 allele 20 of 20 of 21 rs2273773 21 rs2273773 22 in 22 in 23 men 25 carried 30 hypertension 26 a 30 hypertension 27 high 30 hypertension 28 risk 30 hypertension the [t] allele of rs2273773 in men carried a high risk for hyperglycemia . 0 ###LEFT-WALL### 3 allele 0 ###LEFT-WALL### 8 carried 0 ###LEFT-WALL### 14 . 1 the 3 allele 3 allele 4 of 3 allele 8 carried 4 of 5 rs2273773 5 rs2273773 6 in 6 in 7 men 8 carried 11 risk 9 a 10 high 9 a 11 risk 10 high 11 risk 11 risk 12 for 12 for 13 hyperglycemia in conclusion , these sirt1 gene polymorphisms are associated with high body fat and blood pressure in japanese , especially in men . 0 ###LEFT-WALL### 2 conclusion 0 ###LEFT-WALL### 3 , 1 in 2 conclusion 3 , 7 polymorphisms 3 , 9 associated 4 these 7 polymorphisms 5 sirt1 6 gene 6 gene 7 polymorphisms 7 polymorphisms 8 are 8 are 9 associated 9 associated 10 with 9 associated 17 in 10 with 14 and 11 high 13 fat 12 body 13 fat 13 fat 14 and 14 and 16 pressure 15 blood 16 pressure 17 in 18 japanese 18 japanese 21 in 19 , 20 especially 19 , 21 in 21 in 22 men 21 in 23 . the allele frequencies of rs7895833 and rs7069102 , which are different from caucasians , might explain why japanese show less marked obesity compared with caucasians . 0 ###LEFT-WALL### 3 frequencies 0 ###LEFT-WALL### 16 explain 0 ###LEFT-WALL### 26 . 1 the 3 frequencies 2 allele 3 frequencies 3 frequencies 4 of 3 frequencies 15 might 4 of 6 and 5 rs7895833 6 and 6 and 7 rs7069102 6 and 9 which 8 , 9 which 9 which 10 are 9 which 14 , 10 are 11 different 11 different 12 from 12 from 13 caucasians 15 might 16 explain 16 explain 17 why 17 why 22 obesity 17 why 23 compared 18 japanese 19 show 19 show 22 obesity 20 less 21 marked 21 marked 22 obesity 22 obesity 23 compared 23 compared 24 with 24 with 25 caucasians [none] none background : it is generally acknowledged that back pain ( bp ) is a common condition already in childhood . 0 ###LEFT-WALL### 3 background 0 ###LEFT-WALL### 4 : 2 none 3 background 4 : 5 it 4 : 8 acknowledged 4 : 22 . 5 it 6 is 6 is 7 generally 6 is 8 acknowledged 8 acknowledged 9 that 9 that 11 pain 9 that 15 is 10 back 11 pain 11 pain 13 bp 11 pain 15 is 12 ( 13 bp 13 bp 14 ) 15 is 18 condition 15 is 19 already 15 is 20 in 16 a 17 common 16 a 18 condition 17 common 18 condition 20 in 21 childhood however , the development until early adulthood is not well understood [and] , in particular , not the individual tracking pattern . 0 ###LEFT-WALL### 4 development 0 ###LEFT-WALL### 8 is 1 however 2 , 1 however 4 development 3 the 4 development 4 development 5 until 4 development 8 is 5 until 7 adulthood 6 early 7 adulthood 8 is 9 not 8 is 10 well 10 well 11 understood 10 well 21 pattern 11 understood 15 particular 13 , 15 particular 14 in 15 particular 15 particular 16 , 16 , 17 not 16 , 21 pattern 18 the 21 pattern 19 individual 21 pattern 20 tracking 21 pattern 21 pattern 22 . the objectives of this paper are to show the prevalence estimates of bp , low back pain ( lbp ) , mid back pain ( mbp ) , neck pain ( np ) , and care - seeking because of bp at three different ages ( 9 , 13 and 15 years ) and how the bp reporting tracks over these age groups over three consecutive surveys . 0 ###LEFT-WALL### 2 objectives 0 ###LEFT-WALL### 6 are 0 ###LEFT-WALL### 68 . 1 the 2 objectives 2 objectives 3 of 2 objectives 6 are 3 of 5 paper 4 this 5 paper 6 are 7 to 7 to 8 show 8 show 10 prevalence 8 show 35 and 9 the 10 prevalence 11 estimates 12 of 11 estimates 35 and 12 of 13 bp 13 bp 17 pain 14 , 17 pain 15 low 17 pain 16 back 17 pain 17 pain 19 lbp 17 pain 24 pain 17 pain 30 pain 17 pain 34 , 18 ( 19 lbp 19 lbp 20 ) 21 , 24 pain 22 mid 23 back 23 back 24 pain 24 pain 26 mbp 24 pain 27 ) 25 ( 26 mbp 26 mbp 27 ) 28 , 30 pain 29 neck 30 pain 30 pain 32 np 30 pain 33 ) 31 ( 32 np 32 np 33 ) 34 , 35 and 35 and 36 care 35 and 37 - 35 and 38 seeking 38 seeking 39 because 38 seeking 57 bp 38 seeking 60 over 38 seeking 64 over 39 because 40 of 40 of 54 and 41 bp 42 at 41 bp 54 and 42 at 45 ages 43 three 45 ages 44 different 45 ages 45 ages 47 9 45 ages 52 years 46 ( 47 9 47 9 48 , 48 , 52 years 49 13 50 and 50 and 51 15 50 and 52 years 52 years 53 ) 54 and 55 how 56 the 57 bp 57 bp 58 reporting 58 reporting 59 tracks 60 over 63 groups 61 these 63 groups 62 age 63 groups 64 over 67 surveys 65 three 67 surveys 66 consecutive 67 surveys methods : a longitudinal cohort study was carried out from the years of 1997 till 2005 , collecting interview data from children who were sampled to be representative of danish schoolchildren . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 6 study 2 : 8 carried 2 : 32 . 3 a 6 study 4 longitudinal 5 cohort 5 cohort 6 study 6 study 7 was 7 was 8 carried 8 carried 9 out 8 carried 10 from 10 from 12 years 11 the 12 years 12 years 20 data 12 years 31 schoolchildren 13 of 15 till 13 of 17 , 13 of 20 data 14 1997 15 till 15 till 16 2005 18 collecting 19 interview 19 interview 20 data 20 data 21 from 20 data 23 who 20 data 24 were 20 data 31 schoolchildren 21 from 22 children 23 who 24 were 24 were 25 sampled 25 sampled 26 to 26 to 27 be 27 be 28 representative 28 representative 29 of 29 of 30 danish bp was defined overall and specifically in the three spinal regions as having reported pain within the past month . 0 ###LEFT-WALL### 1 bp 0 ###LEFT-WALL### 3 defined 0 ###LEFT-WALL### 5 and 0 ###LEFT-WALL### 20 . 1 bp 2 was 2 was 3 defined 3 defined 4 overall 5 and 6 specifically 5 and 11 regions 5 and 14 reported 7 in 9 three 7 in 11 regions 8 the 9 three 10 spinal 11 regions 11 regions 12 as 11 regions 14 reported 12 as 13 having 14 reported 15 pain 14 reported 16 within 16 within 19 month 17 the 19 month 18 past 19 month the prevalence estimates and the various patterns of bp reporting over time are presented as percentages . 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 14 presented 0 ###LEFT-WALL### 17 . 1 the 3 estimates 2 prevalence 3 estimates 3 estimates 4 and 4 and 7 patterns 4 and 8 of 4 and 13 are 5 the 7 patterns 6 various 7 patterns 8 of 9 bp 9 bp 10 reporting 10 reporting 11 over 11 over 12 time 13 are 14 presented 14 presented 15 as 15 as 16 percentages results : of the 771 children sampled , 62 % , 57 % , and 58 % participated in the three back surveys and 34 % participated in all three . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 15 and 0 ###LEFT-WALL### 31 . 1 results 2 : 2 : 3 of 3 of 6 children 4 the 5 771 5 771 6 children 6 children 7 sampled 6 children 10 % 8 , 10 % 9 62 10 % 10 % 13 % 10 % 14 , 11 , 13 % 12 57 13 % 13 % 14 , 15 and 26 % 15 and 27 participated 16 58 17 % 16 58 24 and 17 % 18 participated 18 participated 19 in 19 in 23 surveys 20 the 21 three 21 three 23 surveys 22 back 23 surveys 24 and 25 34 24 and 26 % 26 % 27 participated 27 participated 28 in 28 in 30 three 29 all 30 three the prevalence estimates [for] children at the ages of 9 , 13 , and 15 , respectively , were for bp 33 % , 28 % , and 48 % [;] for lbp 4 % , 22 % , and 36 % [;] for mbp 20 % , 13 % , and 35 % [;] and [for] np 10 % , 7 % , and 15 % . 0 ###LEFT-WALL### 2 prevalence 0 ###LEFT-WALL### 3 estimates 0 ###LEFT-WALL### 11 , 1 the 2 prevalence 2 prevalence 3 estimates 3 estimates 5 children 3 estimates 6 at 6 at 8 ages 7 the 8 ages 8 ages 9 of 9 of 10 9 11 , 12 13 11 , 14 and 13 , 14 and 14 and 15 15 14 and 19 were 15 15 19 were 16 , 17 respectively 17 respectively 18 , 17 respectively 19 were 19 were 20 for 20 for 21 bp 21 bp 28 and 21 bp 32 for 22 33 23 % 22 33 28 and 23 % 26 % 24 , 26 % 25 28 26 % 26 % 27 , 28 and 29 48 29 48 30 % 32 for 42 % 33 lbp 40 and 34 4 35 % 34 4 40 and 35 % 38 % 36 , 38 % 37 22 38 % 38 % 39 , 40 and 41 36 41 36 42 % 42 % 44 for 44 for 56 and 45 mbp 52 and 45 mbp 56 and 46 20 47 % 46 20 52 and 47 % 50 % 48 , 50 % 49 13 50 % 50 % 51 , 52 and 53 35 53 35 54 % 56 and 58 np 56 and 68 . 58 np 65 and 59 10 60 % 59 10 65 and 60 % 63 % 61 , 63 % 62 7 63 % 63 % 64 , 65 and 66 15 66 15 67 % seeking care for bp increased from 6 % and 8 % at the two youngest ages to 34 % at the oldest . 0 ###LEFT-WALL### 1 seeking 0 ###LEFT-WALL### 5 increased 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 23 . 1 seeking 2 care 1 seeking 5 increased 2 care 3 for 3 for 4 bp 5 increased 6 from 6 from 8 % 7 6 8 % 9 and 11 % 9 and 16 ages 10 8 11 % 11 % 12 at 11 % 16 ages 12 at 15 youngest 13 the 15 youngest 14 two 15 youngest 16 ages 17 to 16 ages 20 at 17 to 19 % 18 34 19 % 20 at 22 oldest 21 the 22 oldest only 7 % of the children who participated in all three surveys reported bp each time and 30 % of these always reported no pain . 0 ###LEFT-WALL### 19 % 0 ###LEFT-WALL### 23 reported 0 ###LEFT-WALL### 26 . 1 only 2 7 2 7 3 % 2 7 17 and 3 % 4 of 3 % 7 who 3 % 8 participated 3 % 13 reported 4 of 6 children 5 the 6 children 7 who 8 participated 8 participated 9 in 9 in 12 surveys 10 all 11 three 11 three 12 surveys 13 reported 14 bp 13 reported 16 time 15 each 16 time 17 and 18 30 17 and 19 % 19 % 20 of 19 % 23 reported 20 of 21 these 22 always 23 reported 23 reported 25 pain 24 no 25 pain the patterns of development differed for the three spinal regions and between genders . 0 ###LEFT-WALL### 2 patterns 0 ###LEFT-WALL### 5 differed 0 ###LEFT-WALL### 14 . 1 the 2 patterns 2 patterns 3 of 2 patterns 5 differed 3 of 4 development 5 differed 11 and 6 for 10 regions 6 for 11 and 7 the 8 three 8 three 10 regions 9 spinal 10 regions 11 and 12 between 12 between 13 genders status at the previous survey predicted status at the next survey , [so] that those who had pain before were more likely to report pain again and vice versa . 0 ###LEFT-WALL### 27 and 0 ###LEFT-WALL### 30 . 1 status 2 at 1 status 27 and 2 at 7 status 3 the 4 previous 3 the 7 status 5 survey 6 predicted 6 predicted 7 status 7 status 8 at 7 status 22 likely 8 at 11 survey 9 the 10 next 9 the 11 survey 11 survey 14 that 11 survey 20 were 12 , 14 that 14 that 15 those 14 that 20 were 15 those 16 who 15 those 17 had 15 those 20 were 16 who 17 had 17 had 18 pain 17 had 19 before 21 more 22 likely 22 likely 23 to 22 likely 24 report 23 to 24 report 24 report 25 pain 24 report 26 again 27 and 29 versa 28 vice 29 versa this was most pronounced for care - seeking . 0 ###LEFT-WALL### 1 this 0 ###LEFT-WALL### 2 was 0 ###LEFT-WALL### 7 - 0 ###LEFT-WALL### 9 . 1 this 2 was 2 was 3 most 3 most 4 pronounced 4 pronounced 5 for 5 for 6 care 7 - 8 seeking conclusion : it was confirmed that bp starts early in life , but the patterns of onset [and] development over time vary for different parts of the spine and between genders . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 3 it 2 : 5 confirmed 2 : 13 but 2 : 32 . 3 it 4 was 4 was 5 confirmed 5 confirmed 6 that 6 that 7 bp 6 that 8 starts 7 bp 8 starts 8 starts 9 early 8 starts 10 in 10 in 11 life 12 , 13 but 13 but 15 patterns 13 but 22 vary 14 the 15 patterns 15 patterns 16 of 15 patterns 22 vary 16 of 19 development 17 onset 19 development 19 development 20 over 20 over 21 time 22 vary 29 and 23 for 25 parts 23 for 29 and 24 different 25 parts 25 parts 26 of 26 of 28 spine 27 the 28 spine 29 and 30 between 30 between 31 genders because of these differences , it is recommended to report on bp in youngsters separately for the three spinal regions , and to differentiate in the analyses between the genders and age groups . 0 ###LEFT-WALL### 6 it 0 ###LEFT-WALL### 8 recommended 0 ###LEFT-WALL### 34 . 1 because 2 of 1 because 5 , 1 because 6 it 2 of 4 differences 3 these 4 differences 6 it 7 is 7 is 8 recommended 8 recommended 9 to 8 recommended 28 between 9 to 22 and 10 report 11 on 10 report 15 separately 10 report 16 for 10 report 22 and 11 on 12 bp 12 bp 13 in 13 in 14 youngsters 16 for 20 regions 17 the 18 three 18 three 20 regions 19 spinal 20 regions 21 , 22 and 22 and 23 to 22 and 24 differentiate 22 and 25 in 23 to 24 differentiate 25 in 27 analyses 26 the 27 analyses 28 between 31 and 29 the 30 genders 30 genders 31 and 31 and 33 groups 32 age 33 groups although only a small minority reported bp at two or all three surveys , tracking of bp ( particularly np ) and care seeking was noted from one survey to the other . 0 ###LEFT-WALL### 15 tracking 0 ###LEFT-WALL### 26 noted 0 ###LEFT-WALL### 33 . 1 although 2 only 1 although 6 reported 1 although 14 , 1 although 15 tracking 2 only 5 minority 3 a 5 minority 4 small 5 minority 5 minority 6 reported 6 reported 10 or 7 bp 8 at 7 bp 10 or 8 at 9 two 10 or 13 surveys 11 all 12 three 12 three 13 surveys 15 tracking 16 of 15 tracking 25 was 16 of 22 and 17 bp 20 np 17 bp 22 and 18 ( 19 particularly 18 ( 20 np 20 np 21 ) 22 and 24 seeking 23 care 24 seeking 25 was 26 noted 26 noted 27 from 27 from 29 survey 28 one 29 survey 29 survey 30 to 30 to 32 other 31 the 32 other on the positive side , individuals without bp at a previous survey were likely to remain pain free at the subsequent survey . 0 ###LEFT-WALL### 6 individuals 0 ###LEFT-WALL### 13 were 0 ###LEFT-WALL### 23 . 1 on 4 side 1 on 5 , 1 on 6 individuals 2 the 4 side 3 positive 4 side 6 individuals 7 without 6 individuals 13 were 7 without 8 bp 8 bp 9 at 9 at 12 survey 10 a 12 survey 11 previous 12 survey 13 were 14 likely 14 likely 15 to 14 likely 16 remain 15 to 16 remain 16 remain 17 pain 17 pain 18 free 18 free 19 at 19 at 22 survey 20 the 22 survey 21 subsequent 22 survey objective : to determine whether injection every 4 months with onabotulinumtoxina provides longer - lasting reduction or elimination of glabellar rhytides . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 2 : 3 to 2 : 4 determine 2 : 22 . 3 to 4 determine 4 determine 5 whether 5 whether 6 injection 5 whether 12 provides 6 injection 7 every 6 injection 10 with 6 injection 12 provides 7 every 9 months 8 4 9 months 10 with 11 onabotulinumtoxina 12 provides 17 or 13 longer 14 - 13 longer 16 reduction 15 lasting 16 reduction 16 reduction 17 or 17 or 18 elimination 17 or 19 of 19 of 21 rhytides 20 glabellar 21 rhytides methods : toxin - naive women ( n=45 ) aged 30 to 50 with moderate [to] severe glabellar lines at maximum contraction completed the study . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 3 toxin 2 : 10 aged 2 : 26 . 3 toxin 6 women 3 toxin 10 aged 4 - 6 women 5 naive 6 women 6 women 8 n=45 6 women 9 ) 7 ( 8 n=45 8 n=45 9 ) 10 aged 12 to 10 aged 14 with 10 aged 20 at 10 aged 25 study 11 30 12 to 12 to 13 50 14 with 19 lines 15 moderate 19 lines 17 severe 19 lines 18 glabellar 19 lines 20 at 22 contraction 21 maximum 22 contraction 22 contraction 23 completed 24 the 25 study five sites were treated with 4 [u] of onabotulinumtoxina . 0 ###LEFT-WALL### 2 sites 0 ###LEFT-WALL### 4 treated 0 ###LEFT-WALL### 10 . 1 five 2 sites 2 sites 3 were 3 were 4 treated 4 treated 5 with 5 with 6 4 6 4 8 of 8 of 9 onabotulinumtoxina participants were assessed at day 30 ; those with glabellar severity of none [to] [mild] remained in the study . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 3 assessed 0 ###LEFT-WALL### 7 ; 0 ###LEFT-WALL### 20 . 1 participants 2 were 2 were 3 assessed 3 assessed 4 at 4 at 5 day 5 day 6 30 7 ; 8 those 8 those 9 with 8 those 12 of 8 those 16 remained 9 with 11 severity 10 glabellar 11 severity 12 of 13 none 16 remained 17 in 17 in 19 study 18 the 19 study participants received identical treatments at months 4 , 8 , 12 , 16 [,] and 20 , and were assessed without treatment at 24 , 25 , and 26 months . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 18 and 0 ###LEFT-WALL### 31 . 1 participants 18 and 2 received 4 treatments 2 received 5 at 2 received 18 and 3 identical 4 treatments 5 at 6 months 6 months 7 4 6 months 9 8 8 , 9 8 9 8 11 12 9 8 15 and 9 8 17 , 10 , 11 12 11 12 12 , 12 , 15 and 13 16 15 and 15 and 16 20 15 and 17 , 18 and 19 were 19 were 20 assessed 20 assessed 21 without 21 without 28 and 22 treatment 23 at 22 treatment 28 and 23 at 24 24 24 24 26 25 25 , 26 25 26 25 27 , 27 , 28 and 28 and 30 months 29 26 30 months results : baseline [physician] - and participant - rated treatment responders at maximum contraction were 84 [%] and 80 % , respectively , at month 20 [;] and 56 % [and] 58 % , respectively , at [month] 26 . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 6 and 2 : 8 - 3 baseline 6 and 5 - 6 and 6 and 7 participant 8 - 10 treatment 8 - 11 responders 8 - 40 . 9 rated 10 treatment 10 treatment 11 responders 11 responders 12 at 11 responders 22 respectively 11 responders 24 at 11 responders 33 % 11 responders 35 respectively 11 responders 37 at 12 at 20 % 13 maximum 14 contraction 14 contraction 15 were 15 were 18 and 16 84 18 and 18 and 19 80 19 80 20 % 21 , 22 respectively 22 respectively 23 , 24 at 30 % 25 month 28 and 25 month 30 % 26 20 28 and 28 and 29 56 32 58 33 % 34 , 35 respectively 35 respectively 36 , 37 at 39 26 mean changes [from] [physician] - and participant - assessed facial wrinkle scale at maximum contraction from baseline to all postbaseline measurements were [significant] ( p≤.001 ) . 0 ###LEFT-WALL### 1 mean 0 ###LEFT-WALL### 27 . 1 mean 6 and 1 mean 9 assessed 2 changes 6 and 5 - 6 and 6 and 7 participant 6 and 8 - 6 and 9 assessed 9 assessed 12 scale 9 assessed 13 at 9 assessed 16 from 10 facial 11 wrinkle 11 wrinkle 12 scale 13 at 15 contraction 14 maximum 15 contraction 16 from 17 baseline 17 baseline 18 to 17 baseline 21 measurements 17 baseline 22 were 17 baseline 25 p≤.001 18 to 19 all 20 postbaseline 21 measurements 21 measurements 22 were 24 ( 25 p≤.001 25 p≤.001 26 ) the percentage of participants reporting [neutral] ( 0 ) [to] couldn't be more satisfied ( +4 ) with their appearance ranged from 91 % to 100 % during months 1 to 24 . 0 ###LEFT-WALL### 2 percentage 0 ###LEFT-WALL### 21 ranged 0 ###LEFT-WALL### 33 . 1 the 2 percentage 2 percentage 3 of 2 percentage 18 with 2 percentage 21 ranged 3 of 4 participants 4 participants 5 reporting 4 participants 12 be 4 participants 14 satisfied 4 participants 16 +4 5 reporting 8 0 5 reporting 11 couldn't 7 ( 8 0 8 0 9 ) 11 couldn't 12 be 12 be 13 more 15 ( 16 +4 16 +4 17 ) 18 with 20 appearance 19 their 20 appearance 21 ranged 22 from 21 ranged 28 during 21 ranged 31 to 22 from 24 % 23 91 24 % 24 % 25 to 25 to 27 % 26 100 27 % 28 during 29 months 29 months 30 1 31 to 32 24 at [month] 26 , 87 % of participants reported satisfaction , with appearance scores between 0 and +4 . 0 ###LEFT-WALL### 6 % 0 ###LEFT-WALL### 9 reported 1 at 3 26 1 at 4 , 1 at 6 % 5 87 6 % 6 % 7 of 6 % 9 reported 7 of 8 participants 9 reported 10 satisfaction 10 satisfaction 12 with 11 , 12 with 12 with 17 and 12 with 19 . 13 appearance 14 scores 14 scores 15 between 14 scores 17 and 15 between 16 0 17 and 18 +4 no adverse events were reported . 0 ###LEFT-WALL### 3 events 0 ###LEFT-WALL### 5 reported 0 ###LEFT-WALL### 6 . 1 no 3 events 2 adverse 3 events 3 events 4 were 4 were 5 reported conclusions : onabotulinumtoxina delivered for 20 months significantly reduces or progressively eliminates glabellar rhytides for up to 6 months after the last treatment . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 3 onabotulinumtoxina 2 : 10 or 2 : 24 . 3 onabotulinumtoxina 4 delivered 3 onabotulinumtoxina 5 for 3 onabotulinumtoxina 10 or 5 for 7 months 6 20 7 months 8 significantly 9 reduces 9 reduces 10 or 10 or 12 eliminates 10 or 14 rhytides 11 progressively 12 eliminates 13 glabellar 14 rhytides 14 rhytides 15 for 14 rhytides 20 after 15 for 19 months 16 up 17 to 17 to 18 6 18 6 19 months 20 after 23 treatment 21 the 23 treatment 22 last 23 treatment as our understanding of the role of ultraviolet ( uv ) radiation exposure in causing skin cancer continues to be enhanced , it is important that clinicians and researchers are familiar with the various methods for assessing [photodamage] to skin . 0 ###LEFT-WALL### 23 it 0 ###LEFT-WALL### 24 is 0 ###LEFT-WALL### 41 . 1 as 3 understanding 1 as 22 , 1 as 23 it 2 our 3 understanding 3 understanding 4 of 3 understanding 7 of 3 understanding 13 exposure 3 understanding 18 continues 4 of 6 role 5 the 6 role 7 of 12 radiation 8 ultraviolet 10 uv 8 ultraviolet 11 ) 8 ultraviolet 12 radiation 9 ( 10 uv 10 uv 11 ) 13 exposure 14 in 13 exposure 18 continues 14 in 15 causing 15 causing 17 cancer 16 skin 17 cancer 18 continues 19 to 19 to 20 be 20 be 21 enhanced 23 it 24 is 24 is 25 important 25 important 26 that 26 that 28 and 26 that 40 skin 27 clinicians 28 and 28 and 29 researchers 28 and 30 are 30 are 31 familiar 31 familiar 32 with 31 familiar 39 to 31 familiar 40 skin 32 with 35 methods 33 the 35 methods 34 various 35 methods 35 methods 36 for 36 for 37 assessing 39 to 40 skin this paper provides a systematic review of the published literature on invasive and noninvasive methods used to quantify lifetime uv exposure ( ['] photoageing ['] ) . 0 ###LEFT-WALL### 2 paper 0 ###LEFT-WALL### 3 provides 0 ###LEFT-WALL### 27 . 1 this 2 paper 2 paper 3 provides 3 provides 6 review 4 a 5 systematic 4 a 6 review 5 systematic 6 review 6 review 7 of 7 of 10 literature 8 the 10 literature 9 published 10 literature 10 literature 11 on 10 literature 16 used 10 literature 24 photoageing 11 on 15 methods 12 invasive 13 and 13 and 14 noninvasive 13 and 15 methods 16 used 17 to 16 used 18 quantify 17 to 18 quantify 18 quantify 21 exposure 19 lifetime 21 exposure 20 uv 21 exposure 22 ( 24 photoageing 24 photoageing 26 ) clinical examination , histopathology , immunohistochemistry , skin surface topography and ultrasound , in addition to newer technologies such as reflectance confocal microscopy , optical coherence tomography and multiphoton tomography , are reviewed . 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 32 are 0 ###LEFT-WALL### 34 . 1 clinical 2 examination 2 examination 3 , 3 , 4 histopathology 3 , 5 , 5 , 10 topography 5 , 11 and 6 immunohistochemistry 7 , 6 immunohistochemistry 10 topography 8 skin 10 topography 9 surface 10 topography 11 and 12 ultrasound 11 and 14 in 11 and 26 coherence 11 and 32 are 13 , 14 in 14 in 15 addition 14 in 24 , 15 addition 16 to 15 addition 20 as 16 to 18 technologies 17 newer 18 technologies 19 such 20 as 20 as 23 microscopy 21 reflectance 23 microscopy 22 confocal 23 microscopy 24 , 26 coherence 25 optical 26 coherence 26 coherence 28 and 26 coherence 30 tomography 26 coherence 31 , 27 tomography 28 and 28 and 29 multiphoton 28 and 30 tomography 32 are 33 reviewed it is concluded that histopathological solar elastosis alone should not be viewed as a ['] gold standard ['] diagnostic test and that there is no single method available to give accurate quantification of the degenerative changes associated [with] photodamage . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 3 concluded 0 ###LEFT-WALL### 21 and 0 ###LEFT-WALL### 40 . 1 it 2 is 2 is 3 concluded 3 concluded 4 that 4 that 7 elastosis 4 that 12 viewed 5 histopathological 7 elastosis 6 solar 7 elastosis 7 elastosis 9 should 8 alone 9 should 9 should 10 not 9 should 11 be 11 be 12 viewed 12 viewed 13 as 13 as 20 test 14 a 20 test 16 gold 17 standard 17 standard 20 test 19 diagnostic 20 test 21 and 22 that 21 and 24 is 22 that 23 there 22 that 24 is 24 is 27 method 24 is 29 to 25 no 27 method 26 single 27 method 27 method 28 available 29 to 30 give 30 give 32 quantification 31 accurate 32 quantification 32 quantification 33 of 32 quantification 36 changes 32 quantification 39 photodamage 33 of 35 degenerative 34 the 35 degenerative 36 changes 37 associated 36 changes 39 photodamage although additional research into sensitivity and specificity is still needed , skin surface topography currently has the most support in the literature as a valid and reliable noninvasive tool for the assessment of photoageing . 0 ###LEFT-WALL### 14 topography 0 ###LEFT-WALL### 16 has 0 ###LEFT-WALL### 35 . 1 although 3 research 1 although 8 is 1 although 14 topography 2 additional 3 research 3 research 4 into 3 research 8 is 4 into 6 and 5 sensitivity 6 and 6 and 7 specificity 8 is 9 still 10 needed 11 , 10 needed 14 topography 12 skin 14 topography 13 surface 14 topography 14 topography 16 has 15 currently 16 has 16 has 19 support 16 has 20 in 16 has 23 as 17 the 18 most 18 most 19 support 20 in 22 literature 21 the 22 literature 23 as 29 tool 24 a 29 tool 25 valid 26 and 26 and 27 reliable 26 and 29 tool 28 noninvasive 29 tool 29 tool 30 for 29 tool 33 of 30 for 32 assessment 31 the 32 assessment 33 of 34 photoageing aging affects energy homeostasis and fuel metabolism in a form of either an increased body mass and glucose intolerance that may lead to obesity and type 2 diabetes or loss of appetite that also may seriously compromise health status . 0 ###LEFT-WALL### 1 aging 0 ###LEFT-WALL### 2 affects 0 ###LEFT-WALL### 40 . 1 aging 2 affects 2 affects 5 and 2 affects 8 in 3 energy 4 homeostasis 4 homeostasis 5 and 5 and 7 metabolism 6 fuel 7 metabolism 8 in 10 form 9 a 10 form 10 form 11 of 10 form 20 that 10 form 22 lead 11 of 19 intolerance 12 either 19 intolerance 13 an 16 mass 14 increased 15 body 15 body 16 mass 16 mass 17 and 17 and 18 glucose 17 and 19 intolerance 20 that 21 may 21 may 22 lead 22 lead 23 to 23 to 25 and 24 obesity 25 and 25 and 39 status 26 type 28 diabetes 27 2 28 diabetes 28 diabetes 29 or 29 or 30 loss 29 or 31 of 29 or 39 status 31 of 32 appetite 32 appetite 33 that 32 appetite 35 may 33 that 35 may 34 also 35 may 35 may 37 compromise 36 seriously 37 compromise 38 health 39 status the data [,] obtained mainly [in] rat , suggest that aging suppresses the expression and action of potent orexigenic peptides such as [predominantly] neuropeptides npy and orexins as peripheral hormone , ghrelin . 0 ###LEFT-WALL### 2 data 0 ###LEFT-WALL### 8 , 1 the 2 data 2 data 4 obtained 2 data 8 , 5 mainly 7 rat 7 rat 8 , 8 , 9 suggest 8 , 26 and 9 suggest 10 that 10 that 11 aging 10 that 12 suppresses 11 aging 12 suppresses 12 suppresses 15 and 12 suppresses 22 as 13 the 14 expression 14 expression 15 and 15 and 16 action 15 and 17 of 17 of 20 peptides 18 potent 20 peptides 19 orexigenic 20 peptides 21 such 22 as 22 as 24 neuropeptides 25 npy 26 and 26 and 30 hormone 26 and 32 ghrelin 27 orexins 30 hormone 28 as 29 peripheral 29 peripheral 30 hormone 31 , 32 ghrelin 32 ghrelin 33 . senescent animals show over [-] responsiveness to αmsh , the major anorexigenic neuropeptide . 0 ###LEFT-WALL### 2 animals 0 ###LEFT-WALL### 3 show 0 ###LEFT-WALL### 9 , 0 ###LEFT-WALL### 14 . 1 senescent 2 animals 2 animals 3 show 3 show 4 over 3 show 6 responsiveness 3 show 7 to 7 to 8 αmsh 9 , 13 neuropeptide 10 the 13 neuropeptide 11 major 13 neuropeptide 12 anorexigenic 13 neuropeptide however , central anorexigenic action of leptin is clearly diminished in aging , most likely due to the impaired leptin signal transduction . 0 ###LEFT-WALL### 5 action 0 ###LEFT-WALL### 10 diminished 0 ###LEFT-WALL### 23 . 1 however 2 , 1 however 5 action 3 central 5 action 4 anorexigenic 5 action 5 action 6 of 5 action 8 is 6 of 7 leptin 8 is 9 clearly 8 is 10 diminished 10 diminished 11 in 10 diminished 13 , 10 diminished 15 likely 11 in 12 aging 14 most 15 likely 15 likely 17 to 16 due 17 to 17 to 22 transduction 18 the 22 transduction 19 impaired 20 leptin 20 leptin 22 transduction 21 signal 22 transduction the age - related central resistance to leptin and insulin does not reduce their inhibitory effects on the activity of npy and agrp neurons . 0 ###LEFT-WALL### 2 age 0 ###LEFT-WALL### 13 reduce 0 ###LEFT-WALL### 22 and 0 ###LEFT-WALL### 25 . 1 the 2 age 2 age 11 does 3 - 4 related 4 related 6 resistance 4 related 7 to 4 related 11 does 5 central 6 resistance 7 to 9 and 8 leptin 9 and 9 and 10 insulin 11 does 12 not 11 does 13 reduce 13 reduce 16 effects 13 reduce 17 on 14 their 16 effects 15 inhibitory 16 effects 17 on 19 activity 18 the 19 activity 19 activity 20 of 20 of 21 npy 22 and 23 agrp 22 and 24 neurons 23 agrp 24 neurons thus , in rodents aging is associated with the altered expression and activity of both orexigenic and anorexigenic peptides . 0 ###LEFT-WALL### 5 aging 0 ###LEFT-WALL### 7 associated 0 ###LEFT-WALL### 20 . 1 thus 2 , 1 thus 5 aging 3 in 4 rodents 3 in 5 aging 5 aging 6 is 6 is 7 associated 7 associated 8 with 8 with 12 and 9 the 11 expression 10 altered 11 expression 11 expression 12 and 12 and 13 activity 12 and 14 of 14 of 19 peptides 15 both 19 peptides 16 orexigenic 17 and 17 and 18 anorexigenic 17 and 19 peptides if similar changes in the central regulation of food intake occur during human aging , they may partially explain ['] anorexia of aging ['] and loss of body weight observed at the end - of [-] life period . 0 ###LEFT-WALL### 16 they 0 ###LEFT-WALL### 19 explain 0 ###LEFT-WALL### 30 observed 1 if 3 changes 1 if 11 occur 1 if 15 , 1 if 16 they 2 similar 3 changes 3 changes 4 in 3 changes 8 of 3 changes 11 occur 4 in 7 regulation 5 the 7 regulation 6 central 7 regulation 8 of 10 intake 9 food 10 intake 11 occur 12 during 12 during 14 aging 13 human 14 aging 16 they 17 may 17 may 19 explain 18 partially 19 explain 19 explain 25 and 19 explain 30 observed 21 anorexia 22 of 21 anorexia 25 and 22 of 23 aging 25 and 26 loss 25 and 27 of 25 and 30 observed 27 of 29 weight 28 body 29 weight 30 observed 31 at 30 observed 39 . 31 at 33 end 32 the 33 end 33 end 35 of 34 - 35 of 35 of 38 period 35 of 39 . 37 life 38 period additionally , increased plasma cholecystokinin concentrations in healthy old subjects may also contribute to the loss of appetite characteristic for the elderly . 0 ###LEFT-WALL### 6 concentrations 0 ###LEFT-WALL### 13 contribute 0 ###LEFT-WALL### 23 . 1 additionally 2 , 1 additionally 6 concentrations 3 increased 4 plasma 4 plasma 6 concentrations 5 cholecystokinin 6 concentrations 6 concentrations 7 in 6 concentrations 11 may 7 in 10 subjects 8 healthy 10 subjects 9 old 10 subjects 11 may 13 contribute 12 also 13 contribute 13 contribute 14 to 14 to 16 loss 15 the 16 loss 16 loss 17 of 17 of 18 appetite 18 appetite 19 characteristic 19 characteristic 20 for 20 for 22 elderly 21 the 22 elderly further studies of the central and peripheral mechanisms that control food intake during aging may provide novel therapeutic strategies to improve the nutritional status of the elderly . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 16 provide 0 ###LEFT-WALL### 28 . 1 further 2 studies 2 studies 3 of 2 studies 15 may 3 of 8 mechanisms 4 the 8 mechanisms 5 central 6 and 6 and 7 peripheral 6 and 8 mechanisms 8 mechanisms 9 that 8 mechanisms 10 control 9 that 10 control 10 control 12 intake 10 control 13 during 11 food 12 intake 13 during 14 aging 15 may 16 provide 16 provide 19 strategies 16 provide 20 to 17 novel 19 strategies 18 therapeutic 19 strategies 20 to 21 improve 21 improve 24 status 22 the 24 status 23 nutritional 24 status 24 status 25 of 25 of 27 elderly 26 the 27 elderly with advancing age most aspects of the peptidergic regulation of energy balance are altered . 0 ###LEFT-WALL### 1 with 0 ###LEFT-WALL### 13 are 0 ###LEFT-WALL### 15 . 1 with 2 advancing 1 with 13 are 2 advancing 3 age 4 most 5 aspects 5 aspects 6 of 5 aspects 13 are 6 of 9 regulation 7 the 9 regulation 8 peptidergic 9 regulation 9 regulation 10 of 10 of 12 balance 11 energy 12 balance 13 are 14 altered the alteration involves both the peripheral peptides derived from the adipose tissue or the gastrointestinal tract and the peptides of the central nervous system ( brainstem and hypothalamus ) . 0 ###LEFT-WALL### 2 alteration 0 ###LEFT-WALL### 3 involves 0 ###LEFT-WALL### 30 . 1 the 2 alteration 2 alteration 3 involves 3 involves 4 both 3 involves 9 from 4 both 5 the 4 both 7 peptides 5 the 7 peptides 6 peripheral 7 peptides 7 peptides 8 derived 9 from 17 and 10 the 12 tissue 11 adipose 12 tissue 12 tissue 13 or 13 or 16 tract 13 or 17 and 14 the 16 tract 15 gastrointestinal 16 tract 17 and 19 peptides 17 and 20 of 18 the 19 peptides 20 of 24 system 21 the 24 system 22 central 24 system 23 nervous 24 system 24 system 27 and 25 ( 27 and 26 brainstem 27 and 27 and 28 hypothalamus 27 and 29 ) in general , the expression of orexigenic peptides and their receptors decreases with age , while that of the anorexic ones [rather] increases , but not [simultaneously] and not in a linear fashion . 0 ###LEFT-WALL### 5 expression 0 ###LEFT-WALL### 12 decreases 0 ###LEFT-WALL### 34 . 1 in 2 general 2 general 3 , 2 general 5 expression 4 the 5 expression 5 expression 6 of 5 expression 12 decreases 6 of 9 and 7 orexigenic 8 peptides 8 peptides 9 and 9 and 11 receptors 10 their 11 receptors 12 decreases 13 with 12 decreases 16 while 12 decreases 28 and 13 with 14 age 15 , 16 while 16 while 17 that 16 while 23 increases 16 while 24 , 17 that 18 of 17 that 23 increases 18 of 21 ones 19 the 21 ones 20 anorexic 21 ones 25 but 26 not 25 but 28 and 28 and 29 not 28 and 30 in 30 in 33 fashion 31 a 32 linear 31 a 33 fashion 32 linear 33 fashion apart from such quantitative changes , the efficacy of the related peptides may also change with age . 0 ###LEFT-WALL### 8 efficacy 0 ###LEFT-WALL### 15 change 0 ###LEFT-WALL### 18 . 1 apart 2 from 2 from 5 changes 2 from 6 , 2 from 8 efficacy 3 such 5 changes 4 quantitative 5 changes 7 the 8 efficacy 8 efficacy 9 of 8 efficacy 13 may 9 of 12 peptides 10 the 12 peptides 11 related 12 peptides 13 may 15 change 14 also 15 change 15 change 16 with 16 with 17 age these changes are not necessarily linear , either : instead of continuous [decline] or increase of its effects , the effects of a peptide may become [less] pronounced in some phases of aging and [much] enhanced in other ones . 0 ###LEFT-WALL### 2 changes 0 ###LEFT-WALL### 3 are 0 ###LEFT-WALL### 7 , 1 these 2 changes 2 changes 3 are 3 are 4 not 3 are 5 necessarily 3 are 6 linear 7 , 8 either 7 , 9 : 9 : 21 effects 9 : 34 and 9 : 40 . 10 instead 11 of 11 of 14 or 11 of 19 , 11 of 21 effects 12 continuous 14 or 14 or 15 increase 14 or 16 of 16 of 18 effects 17 its 18 effects 20 the 21 effects 21 effects 22 of 21 effects 34 and 22 of 24 peptide 23 a 24 peptide 25 may 26 become 25 may 34 and 26 become 28 pronounced 28 pronounced 29 in 29 in 31 phases 30 some 31 phases 31 phases 32 of 32 of 33 aging 34 and 36 enhanced 34 and 37 in 37 in 39 ones 38 other 39 ones comparing the individual peptides , the phasic alterations in their anabolic or catabolic roles in the regulation of energy balance may exhibit dissimilar time - patterns . 0 ###LEFT-WALL### 8 alterations 0 ###LEFT-WALL### 22 exhibit 0 ###LEFT-WALL### 25 - 1 comparing 4 peptides 1 comparing 5 , 1 comparing 8 alterations 2 the 4 peptides 3 individual 4 peptides 6 the 8 alterations 7 phasic 8 alterations 8 alterations 9 in 8 alterations 18 of 8 alterations 21 may 9 in 14 roles 10 their 14 roles 11 anabolic 12 or 12 or 13 catabolic 12 or 14 roles 14 roles 15 in 15 in 17 regulation 16 the 17 regulation 18 of 20 balance 19 energy 20 balance 21 may 22 exhibit 22 exhibit 24 time 23 dissimilar 24 time 25 - 26 patterns 25 - 27 . in addition , within the overall anabolic or catabolic effects , the feeding and metabolic actions of certain peptides may not change simultaneously . 0 ###LEFT-WALL### 14 and 0 ###LEFT-WALL### 22 change 0 ###LEFT-WALL### 24 . 1 in 2 addition 1 in 3 , 1 in 14 and 4 within 6 overall 4 within 14 and 5 the 6 overall 7 anabolic 8 or 8 or 9 catabolic 8 or 10 effects 10 effects 11 , 11 , 13 feeding 11 , 14 and 12 the 13 feeding 14 and 16 actions 14 and 17 of 14 and 20 may 15 metabolic 16 actions 17 of 19 peptides 18 certain 19 peptides 20 may 21 not 20 may 22 change 22 change 23 simultaneously aging in mammals associates with the development of peripheral insulin resistance . 0 ###LEFT-WALL### 1 aging 0 ###LEFT-WALL### 4 associates 0 ###LEFT-WALL### 12 . 1 aging 2 in 1 aging 4 associates 2 in 3 mammals 4 associates 5 with 5 with 7 development 6 the 7 development 7 development 8 of 8 of 11 resistance 9 peripheral 10 insulin 10 insulin 11 resistance additionally , adiposity usually increases with aging and this could play a relevant role in the gradual impairment of insulin action . 0 ###LEFT-WALL### 3 adiposity 0 ###LEFT-WALL### 5 increases 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 22 . 1 additionally 2 , 1 additionally 3 adiposity 3 adiposity 5 increases 4 usually 5 increases 5 increases 6 with 6 with 7 aging 8 and 9 this 8 and 11 play 9 this 10 could 10 could 11 play 11 play 14 role 11 play 15 in 12 a 13 relevant 12 a 14 role 13 relevant 14 role 15 in 18 impairment 16 the 18 impairment 17 gradual 18 impairment 18 impairment 19 of 19 of 21 action 20 insulin 21 action in fact , fat accretion leads to changes in the expression and circulating concentrations of factors originated in adipose tissue like leptin , resistin and inflammatory cytokines which have been shown to modulate insulin signaling in insulin target tissues acting both , [directly] or through the central nervous system . 0 ###LEFT-WALL### 21 like 0 ###LEFT-WALL### 50 . 1 in 12 and 1 in 21 like 2 fact 3 , 3 , 6 leads 3 , 12 and 4 fat 5 accretion 5 accretion 6 leads 6 leads 7 to 7 to 8 changes 8 changes 9 in 9 in 11 expression 10 the 11 expression 12 and 14 concentrations 13 circulating 14 concentrations 14 concentrations 15 of 15 of 16 factors 16 factors 17 originated 17 originated 18 in 18 in 20 tissue 19 adipose 20 tissue 21 like 25 and 21 like 32 to 21 like 44 or 22 leptin 23 , 23 , 24 resistin 23 , 25 and 25 and 27 cytokines 25 and 28 which 25 and 29 have 26 inflammatory 27 cytokines 28 which 29 have 29 have 30 been 30 been 31 shown 32 to 33 modulate 33 modulate 34 insulin 34 insulin 35 signaling 36 in 39 tissues 36 in 44 or 37 insulin 38 target 38 target 39 tissues 39 tissues 40 acting 40 acting 41 both 42 , 44 or 44 or 45 through 45 through 49 system 46 the 49 system 47 central 49 system 48 nervous 49 system even insulin action on peripheral target tissues has been recently demonstrated to be partially mediated by its central action , suggesting that a decrease in central insulin action could be involved in the development of peripheral insulin resistance . 0 ###LEFT-WALL### 3 action 0 ###LEFT-WALL### 11 demonstrated 0 ###LEFT-WALL### 20 , 0 ###LEFT-WALL### 39 . 1 even 2 insulin 2 insulin 3 action 3 action 4 on 3 action 8 has 4 on 7 tissues 5 peripheral 6 target 6 target 7 tissues 8 has 9 been 9 been 10 recently 9 been 11 demonstrated 11 demonstrated 12 to 12 to 13 be 13 be 15 mediated 14 partially 15 mediated 15 mediated 16 by 16 by 19 action 17 its 19 action 18 central 19 action 20 , 21 suggesting 20 , 31 involved 21 suggesting 22 that 21 suggesting 31 involved 22 that 24 decrease 22 that 30 be 23 a 24 decrease 24 decrease 25 in 24 decrease 29 could 25 in 28 action 26 central 27 insulin 27 insulin 28 action 29 could 30 be 31 involved 32 in 31 involved 38 resistance 32 in 34 development 33 the 34 development 34 development 35 of 35 of 37 insulin 36 peripheral 37 insulin aim : to investigate sex [hormone] and androgen receptor ( ar ) levels and to evaluate their relationship with diabetes mellitus ( dm ) in senile men . 0 ###LEFT-WALL### 1 aim 0 ###LEFT-WALL### 2 : 2 : 3 to 2 : 14 and 2 : 28 . 3 to 14 and 4 investigate 13 levels 4 investigate 14 and 5 sex 7 and 7 and 9 receptor 7 and 11 ar 7 and 13 levels 8 androgen 9 receptor 10 ( 11 ar 11 ar 12 ) 14 and 15 to 14 and 16 evaluate 14 and 25 in 15 to 16 evaluate 16 evaluate 18 relationship 16 evaluate 19 with 17 their 18 relationship 19 with 21 mellitus 20 diabetes 21 mellitus 21 mellitus 23 dm 22 ( 23 dm 23 dm 24 ) 25 in 27 men 26 senile 27 men methods : the cross - sectional study included 492 elderly men comprising 104 healthy subjects ( mean age 71.4 ± 5.2 years ) , 259 subjects without dm ( 71.5 ± 5.0 years ) and 129 dm patients ( 73.0 ± 6.3 years ) . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 5 - 0 ###LEFT-WALL### 45 . 1 methods 2 : 2 : 4 cross 3 the 4 cross 5 - 7 study 5 - 8 included 6 sectional 7 study 7 study 8 included 8 included 11 men 9 492 11 men 10 elderly 11 men 11 men 12 comprising 12 comprising 15 subjects 13 104 15 subjects 14 healthy 15 subjects 15 subjects 22 years 15 subjects 26 subjects 16 ( 22 years 17 mean 18 age 18 age 22 years 19 71.4 22 years 20 ± 22 years 21 5.2 22 years 22 years 23 ) 24 , 26 subjects 25 259 26 subjects 26 subjects 27 without 26 subjects 44 ) 27 without 35 and 28 dm 33 years 28 dm 35 and 29 ( 33 years 30 71.5 33 years 31 ± 33 years 32 5.0 33 years 33 years 34 ) 35 and 38 patients 35 and 43 years 36 129 38 patients 37 dm 38 patients 39 ( 43 years 40 73.0 41 ± 41 ± 43 years 42 6.3 43 years 43 years 44 ) plasma concentrations of total testosterone ( tt ) , free testosterone ( ft ) , dehydroepiandrosterone sulphate , sex [hormone] - binding globulin ( shbg ) , estradiol [(] e ( 2 ) ) , luteinising hormone [ )(and follicle - stimulating hormone ( fsh ) were determined . 0 ###LEFT-WALL### 39 )(and 0 ###LEFT-WALL### 49 . 1 plasma 2 concentrations 2 concentrations 3 of 2 concentrations 35 , 3 of 11 testosterone 4 total 11 testosterone 5 testosterone 7 tt 5 testosterone 9 , 5 testosterone 11 testosterone 6 ( 7 tt 7 tt 8 ) 10 free 11 testosterone 11 testosterone 13 ft 11 testosterone 17 sulphate 11 testosterone 19 sex 12 ( 13 ft 13 ft 14 ) 15 , 17 sulphate 16 dehydroepiandrosterone 17 sulphate 17 sulphate 18 , 18 , 19 sex 19 sex 22 binding 19 sex 34 ) 21 - 22 binding 22 binding 23 globulin 22 binding 34 ) 23 globulin 25 shbg 23 globulin 28 estradiol 24 ( 25 shbg 25 shbg 26 ) 27 , 28 estradiol 28 estradiol 30 e 28 estradiol 32 2 28 estradiol 33 ) 31 ( 32 2 32 2 33 ) 35 , 37 hormone 35 , 39 )(and 36 luteinising 37 hormone 39 )(and 43 hormone 39 )(and 45 fsh 39 )(and 47 were 40 follicle 41 - 40 follicle 43 hormone 42 stimulating 43 hormone 44 ( 45 fsh 45 fsh 46 ) 47 were 48 determined ar - positive cells were measured by flow cytometry . 0 ###LEFT-WALL### 4 cells 0 ###LEFT-WALL### 5 were 0 ###LEFT-WALL### 10 . 1 ar 2 - 1 ar 4 cells 3 positive 4 cells 4 cells 5 were 5 were 6 measured 6 measured 7 by 7 by 9 cytometry 8 flow 9 cytometry ft , shbg , ar - positive proportion ( ar [%] ) and ar fluorescence intensity showed a decreasing trend among the healthy , [non] - dm and dm groups , but the differences were not significant . 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 17 showed 0 ###LEFT-WALL### 24 , 0 ###LEFT-WALL### 38 . 1 ft 3 shbg 2 , 3 shbg 3 shbg 4 , 4 , 5 ar 4 , 13 and 5 ar 8 proportion 6 - 8 proportion 7 positive 8 proportion 8 proportion 10 ar 8 proportion 12 ) 9 ( 10 ar 10 ar 12 ) 13 and 16 intensity 13 and 17 showed 14 ar 16 intensity 15 fluorescence 16 intensity 17 showed 20 trend 17 showed 21 among 18 a 20 trend 19 decreasing 20 trend 21 among 23 healthy 22 the 23 healthy 24 , 26 - 24 , 30 groups 24 , 32 but 26 - 29 dm 27 dm 28 and 28 and 29 dm 29 dm 30 groups 31 , 32 but 32 but 34 differences 32 but 35 were 33 the 34 differences 34 differences 35 were 35 were 36 not 35 were 37 significant 36 not 37 significant tt [,] [e] ( 2 ) , [e] [(] 2 )/testosterone and shbg were negatively correlated with blood glucose . 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 16 correlated 0 ###LEFT-WALL### 20 . 1 tt 5 2 1 tt 7 , 4 ( 5 2 5 2 6 ) 7 , 11 )/testosterone 7 , 12 and 10 2 11 )/testosterone 12 and 13 shbg 12 and 14 were 14 were 16 correlated 15 negatively 16 correlated 16 correlated 17 with 17 with 19 glucose 18 blood 19 glucose shbg was positively correlated and tt and ar [%] were negatively correlated with the course of dm . 0 ###LEFT-WALL### 1 shbg 0 ###LEFT-WALL### 4 correlated 0 ###LEFT-WALL### 5 and 0 ###LEFT-WALL### 18 . 1 shbg 2 was 2 was 3 positively 2 was 4 correlated 5 and 7 and 5 and 12 correlated 6 tt 7 and 7 and 8 ar 7 and 10 were 10 were 12 correlated 11 negatively 12 correlated 12 correlated 13 with 13 with 15 course 14 the 15 course 15 course 16 of 16 of 17 dm logistic multiple regression analysis revealed that age , waist/hip ratio , fsh , shbg and ar [%] are potential risk factors for dm . 0 ###LEFT-WALL### 4 analysis 0 ###LEFT-WALL### 5 revealed 0 ###LEFT-WALL### 24 . 1 logistic 4 analysis 2 multiple 4 analysis 3 regression 4 analysis 4 analysis 5 revealed 5 revealed 6 that 6 that 15 and 6 that 18 are 7 age 8 , 8 , 10 ratio 8 , 11 , 9 waist/hip 10 ratio 11 , 12 fsh 11 , 13 , 13 , 14 shbg 13 , 15 and 15 and 16 ar 15 and 18 are 18 are 21 factors 18 are 22 for 19 potential 21 factors 20 risk 21 factors 22 for 23 dm conclusions : low levels of tt , shbg and ar may be potential risk factors for dm in elderly men . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 9 and 2 : 12 be 2 : 21 . 3 low 4 levels 4 levels 5 of 4 levels 9 and 5 of 8 shbg 6 tt 8 shbg 7 , 8 shbg 9 and 10 ar 9 and 11 may 11 may 12 be 12 be 15 factors 13 potential 15 factors 14 risk 15 factors 15 factors 16 for 16 for 17 dm 17 dm 18 in 18 in 20 men 19 elderly 20 men whereas aging affects cognitive and psychomotor processes negatively , the impact of aging on emotional processing is less clear . 0 ###LEFT-WALL### 11 impact 0 ###LEFT-WALL### 17 is 0 ###LEFT-WALL### 20 . 1 whereas 2 aging 1 whereas 3 affects 1 whereas 11 impact 2 aging 3 affects 3 affects 5 and 4 cognitive 5 and 5 and 7 processes 6 psychomotor 7 processes 8 negatively 9 , 8 negatively 11 impact 10 the 11 impact 11 impact 12 of 11 impact 17 is 12 of 13 aging 13 aging 14 on 14 on 16 processing 15 emotional 16 processing 17 is 19 clear 18 less 19 clear using an " old - new " binary decision task , we ascertained the modulation of response latencies after presentation of neutral and emotional pictures in " young " ( m = 27.1 years ) and " young - old " adults with a mean age below 60 ( m = 57.7 years ) . 0 ###LEFT-WALL### 12 we 0 ###LEFT-WALL### 13 ascertained 0 ###LEFT-WALL### 55 . 1 using 10 task 1 using 11 , 1 using 12 we 2 an 3 " 2 an 10 task 4 old 5 - 4 old 8 binary 6 new 7 " 6 new 8 binary 8 binary 10 task 9 decision 10 task 12 we 13 ascertained 13 ascertained 15 modulation 13 ascertained 43 with 14 the 15 modulation 15 modulation 16 of 15 modulation 21 of 16 of 18 latencies 17 response 18 latencies 18 latencies 19 after 19 after 20 presentation 21 of 36 and 22 neutral 23 and 23 and 25 pictures 23 and 35 ) 23 and 36 and 24 emotional 25 pictures 25 pictures 26 in 26 in 27 " 26 in 34 years 28 young 29 " 28 young 32 = 28 young 34 years 30 ( 32 = 31 m 32 = 32 = 33 27.1 36 and 37 " 36 and 42 adults 38 young 39 - 38 young 40 old 40 old 41 " 40 old 42 adults 43 with 46 age 44 a 46 age 45 mean 46 age 46 age 47 below 46 age 51 = 48 60 51 = 49 ( 51 = 50 m 51 = 51 = 53 years 51 = 54 ) 52 57.7 53 years stimuli varied on [valence] [(] pleasant , neutral , and unpleasant ) and arousal ( high and low ) dimensions . 0 ###LEFT-WALL### 1 stimuli 0 ###LEFT-WALL### 2 varied 0 ###LEFT-WALL### 21 . 1 stimuli 2 varied 2 varied 3 on 3 on 13 and 6 pleasant 7 , 7 , 8 neutral 7 , 10 and 9 , 10 and 10 and 11 unpleasant 10 and 12 ) 10 and 13 and 13 and 20 dimensions 14 arousal 17 and 14 arousal 20 dimensions 15 ( 17 and 16 high 17 and 17 and 18 low 17 and 19 ) young - old adults had significantly longer reaction times . 0 ###LEFT-WALL### 4 adults 0 ###LEFT-WALL### 5 had 0 ###LEFT-WALL### 10 . 1 young 2 - 1 young 4 adults 3 old 4 adults 4 adults 5 had 5 had 9 times 6 significantly 7 longer 7 longer 8 reaction 8 reaction 9 times however , young and young - old adults showed the exact same [pattern] of response time modulation by emotional stimuli : response latencies were longer for high - arousal than for low - arousal pictures and longer [for] negative than for positive or neutral stimuli . 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 9 showed 1 however 2 , 1 however 4 and 3 young 4 and 4 and 8 adults 4 and 9 showed 5 young 6 - 5 young 7 old 7 old 8 adults 9 showed 11 exact 9 showed 12 same 10 the 11 exact 12 same 14 of 14 of 16 time 15 response 16 time 16 time 17 modulation 16 time 21 : 16 time 29 arousal 17 modulation 18 by 17 modulation 21 : 18 by 20 stimuli 19 emotional 20 stimuli 21 : 22 response 21 : 27 high 22 response 23 latencies 22 response 26 for 23 latencies 24 were 24 were 25 longer 25 longer 26 for 28 - 29 arousal 29 arousal 30 than 29 arousal 40 than 29 arousal 46 . 30 than 31 for 31 for 36 and 32 low 33 - 32 low 35 pictures 34 arousal 35 pictures 35 pictures 36 and 36 and 39 negative 37 longer 39 negative 40 than 41 for 41 for 43 or 42 positive 43 or 43 or 45 stimuli 44 neutral 45 stimuli this result suggests that the specific effects of implicitly processed emotional [valence] and arousal information on behavioral response time are preserved in young - old adults despite significant age - related psychomotor decline . 0 ###LEFT-WALL### 2 result 0 ###LEFT-WALL### 3 suggests 0 ###LEFT-WALL### 30 - 0 ###LEFT-WALL### 34 . 1 this 2 result 2 result 3 suggests 3 suggests 4 that 4 that 7 effects 4 that 21 preserved 5 the 7 effects 6 specific 7 effects 7 effects 8 of 7 effects 16 on 7 effects 20 are 8 of 15 information 9 implicitly 10 processed 10 processed 15 information 11 emotional 13 and 13 and 14 arousal 13 and 15 information 16 on 19 time 17 behavioral 18 response 18 response 19 time 20 are 21 preserved 21 preserved 22 in 21 preserved 27 despite 22 in 26 adults 23 young 24 - 23 young 26 adults 25 old 26 adults 27 despite 29 age 28 significant 29 age 30 - 33 decline 31 related 32 psychomotor 32 psychomotor 33 decline the purpose of this work was to evaluate the effect of flame - generated nucleation mode particles with an organic carbon structure on growth and apoptosis in immortalized human keratinocytes . 1 the 2 purpose 2 purpose 3 of 2 purpose 6 was 3 of 5 work 4 this 5 work 6 was 7 to 6 was 8 evaluate 7 to 8 evaluate 8 evaluate 10 effect 9 the 10 effect 10 effect 11 of 11 of 12 flame 12 flame 17 particles 13 - 17 particles 14 generated 15 nucleation 15 nucleation 17 particles 16 mode 17 particles 17 particles 18 with 17 particles 23 on 17 particles 27 in 17 particles 31 . 18 with 22 structure 19 an 20 organic 19 an 22 structure 20 organic 21 carbon 21 carbon 22 structure 23 on 25 and 24 growth 25 and 25 and 26 apoptosis 27 in 30 keratinocytes 28 immortalized 30 keratinocytes 29 human 30 keratinocytes in this study , cells were stimulated with nanoparticles collected from flames that produce only nucleation mode particles operating with a fuel:air mixture typical of low - emission combustion systems . 0 ###LEFT-WALL### 5 cells 0 ###LEFT-WALL### 10 collected 0 ###LEFT-WALL### 31 . 1 in 3 study 1 in 4 , 1 in 5 cells 2 this 3 study 5 cells 6 were 6 were 7 stimulated 7 stimulated 8 with 8 with 9 nanoparticles 8 with 10 collected 10 collected 11 from 10 collected 24 typical 11 from 12 flames 12 flames 13 that 12 flames 14 produce 13 that 14 produce 14 produce 15 only 14 produce 18 particles 16 nucleation 17 mode 17 mode 18 particles 18 particles 19 operating 19 operating 20 with 20 with 23 mixture 21 a 22 fuel:air 21 a 23 mixture 22 fuel:air 23 mixture 24 typical 25 of 25 of 30 systems 26 low 27 - 26 low 28 emission 28 emission 30 systems 29 combustion 30 systems cytotoxicity as a function of particle concentration was monitored by fluorescence - activated cell sorting [(] facs ) analysis , and apoptosis [was] observed by facs using dna fragmentation and hypodiploidism and confirmed [by] annexin assay . 0 ###LEFT-WALL### 1 cytotoxicity 0 ###LEFT-WALL### 9 monitored 0 ###LEFT-WALL### 24 observed 1 cytotoxicity 2 as 1 cytotoxicity 8 was 2 as 4 function 3 a 4 function 4 function 5 of 5 of 7 concentration 6 particle 7 concentration 8 was 9 monitored 9 monitored 10 by 10 by 11 fluorescence 11 fluorescence 17 facs 12 - 17 facs 13 activated 14 cell 14 cell 17 facs 15 sorting 17 facs 17 facs 18 ) 19 analysis 21 and 20 , 21 and 21 and 22 apoptosis 21 and 24 observed 24 observed 25 by 24 observed 37 . 25 by 26 facs 26 facs 27 using 27 using 32 and 28 dna 29 fragmentation 29 fragmentation 30 and 30 and 31 hypodiploidism 30 and 32 and 32 and 36 assay 33 confirmed 35 annexin 35 annexin 36 assay a dose - dependent reduction in cell viability by apoptosis in incubation periods of 48 and 72 hours was observed with a statistically significant increase in apoptosis over controls for a dose larger than 7 μg / [ml] ( 1.4 [μg] / cm² ) . 0 ###LEFT-WALL### 2 dose 0 ###LEFT-WALL### 3 - 1 a 2 dose 3 - 5 reduction 3 - 20 observed 3 - 45 . 4 dependent 5 reduction 5 reduction 6 in 5 reduction 9 by 5 reduction 11 in 5 reduction 14 of 5 reduction 19 was 6 in 8 viability 7 cell 8 viability 9 by 10 apoptosis 11 in 13 periods 12 incubation 13 periods 14 of 18 hours 15 48 16 and 16 and 17 72 16 and 18 hours 19 was 20 observed 20 observed 21 with 20 observed 26 in 20 observed 28 over 20 observed 30 for 21 with 25 increase 22 a 23 statistically 22 a 25 increase 23 statistically 24 significant 24 significant 25 increase 26 in 27 apoptosis 28 over 29 controls 30 for 32 dose 31 a 32 dose 32 dose 33 larger 32 dose 43 cm² 33 larger 34 than 34 than 37 / 35 7 36 μg 36 μg 37 / 39 ( 43 cm² 40 1.4 43 cm² 42 / 43 cm² 43 cm² 44 ) the results presented here may be relevant for understanding the association between exposure to traffic - generated particulate pollution and enhanced skin aging reported in epidemiology studies . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 6 be 0 ###LEFT-WALL### 24 reported 0 ###LEFT-WALL### 28 . 1 the 2 results 2 results 3 presented 2 results 5 may 3 presented 4 here 5 may 6 be 6 be 7 relevant 7 relevant 8 for 7 relevant 12 between 7 relevant 14 to 7 relevant 15 traffic 8 for 9 understanding 9 understanding 11 association 10 the 11 association 12 between 13 exposure 14 to 15 traffic 16 - 24 reported 17 generated 18 particulate 18 particulate 19 pollution 19 pollution 20 and 20 and 22 skin 20 and 23 aging 20 and 24 reported 21 enhanced 22 skin 24 reported 25 in 25 in 27 studies 26 epidemiology 27 studies the sitting balance scale ( sbs ) measures sitting balance for frail older adults who are primarily nonambulatory . 0 ###LEFT-WALL### 6 sbs 0 ###LEFT-WALL### 8 measures 0 ###LEFT-WALL### 19 . 1 the 6 sbs 2 sitting 3 balance 3 balance 4 scale 4 scale 6 sbs 5 ( 6 sbs 6 sbs 7 ) 6 sbs 8 measures 8 measures 10 balance 9 sitting 10 balance 10 balance 11 for 11 for 14 adults 12 frail 14 adults 13 older 14 adults 14 adults 15 who 14 adults 16 are 15 who 16 are 16 are 17 primarily 16 are 18 nonambulatory purposes were to generate items representing different functional abilities of sitting balance , reduce the number of items to make a clinically useful tool , refine the assessment , and establish reliability and validity . 0 ###LEFT-WALL### 1 purposes 0 ###LEFT-WALL### 25 , 0 ###LEFT-WALL### 35 . 1 purposes 2 were 2 were 3 to 2 were 13 , 3 to 13 , 4 generate 5 items 4 generate 13 , 5 items 6 representing 6 representing 9 abilities 7 different 9 abilities 8 functional 9 abilities 9 abilities 10 of 10 of 12 balance 11 sitting 12 balance 13 , 14 reduce 13 , 19 to 14 reduce 18 items 15 the 16 number 16 number 17 of 16 number 18 items 17 of 18 items 19 to 25 , 20 make 24 tool 20 make 25 , 21 a 22 clinically 21 a 24 tool 22 clinically 23 useful 23 useful 24 tool 25 , 30 and 26 refine 28 assessment 26 refine 30 and 27 the 28 assessment 29 , 30 and 30 and 31 establish 31 establish 33 and 32 reliability 33 and 33 and 34 validity the study was conducted in multiple phases , with qualitative and quantitative methodologies . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 4 conducted 1 the 2 study 2 study 3 was 3 was 4 conducted 4 conducted 5 in 5 in 7 phases 6 multiple 7 phases 7 phases 9 with 8 , 9 with 9 with 13 methodologies 9 with 14 . 10 qualitative 11 and 11 and 12 quantitative 11 and 13 methodologies content development used nominal group process , expert narratives , and literature review . 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 14 . 1 content 2 development 2 development 5 group 3 used 4 nominal 4 nominal 5 group 5 group 6 process 6 process 7 , 7 , 9 narratives 7 , 11 and 8 expert 9 narratives 10 , 11 and 11 and 13 review 12 literature 13 review after consensus was reached on content and scoring , item reduction began . 0 ###LEFT-WALL### 11 reduction 0 ###LEFT-WALL### 12 began 0 ###LEFT-WALL### 13 . 1 after 2 consensus 1 after 4 reached 1 after 9 , 1 after 11 reduction 2 consensus 3 was 3 was 4 reached 4 reached 5 on 5 on 7 and 6 content 7 and 7 and 8 scoring 10 item 11 reduction 11 reduction 12 began item retention and deletion decisions were based on a combination of practical considerations during field testing , expert and experienced clinician opinion of clinical [relevance] , and statistical information . 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 19 and 0 ###LEFT-WALL### 30 . 1 item 2 retention 2 retention 3 and 3 and 5 decisions 3 and 19 and 4 deletion 5 decisions 6 were 7 based 6 were 19 and 7 based 8 on 7 based 17 , 7 based 18 expert 8 on 10 combination 9 a 10 combination 10 combination 11 of 11 of 13 considerations 12 practical 13 considerations 13 considerations 14 during 14 during 16 testing 15 field 16 testing 19 and 20 experienced 20 experienced 22 opinion 21 clinician 22 opinion 22 opinion 23 of 23 of 29 information 24 clinical 27 and 26 , 27 and 27 and 28 statistical 27 and 29 information item retention or deletion decisions were based in part on the internal consistency analysis of the 19 - item sbs based on 256 scores , which included participants who were apparently healthy and those with pathology . 0 ###LEFT-WALL### 3 or 0 ###LEFT-WALL### 7 based 0 ###LEFT-WALL### 37 . 1 item 2 retention 2 retention 3 or 3 or 5 decisions 3 or 6 were 4 deletion 5 decisions 6 were 7 based 7 based 9 part 8 in 9 part 9 part 10 on 10 on 14 analysis 11 the 14 analysis 12 internal 13 consistency 13 consistency 14 analysis 14 analysis 15 of 14 analysis 26 which 14 analysis 27 included 15 of 17 19 16 the 17 19 17 19 20 sbs 18 - 20 sbs 19 item 20 sbs 20 sbs 21 based 20 sbs 25 , 21 based 22 on 22 on 24 scores 23 256 24 scores 26 which 27 included 27 included 28 participants 27 included 35 with 28 participants 29 who 28 participants 30 were 29 who 30 were 30 were 31 apparently 30 were 33 and 32 healthy 33 and 33 and 34 those 35 with 36 pathology we applied a decision matrix to yield the final 11 - item version . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 11 - 0 ###LEFT-WALL### 14 . 1 we 2 applied 2 applied 5 matrix 2 applied 6 to 3 a 5 matrix 4 decision 5 matrix 6 to 7 yield 7 yield 9 final 8 the 9 final 9 final 10 11 10 11 11 - 11 - 13 version 12 item 13 version the 11 - item sbs demonstrated good internal consistency ( α [=] 0.762 ) , intrarater rater reliability ( icc ( 3,1 ) = 0.96 to 0.99 ) , [and] interrater reliability ( icc ( 2,1 [ )(= 0.87 ) . 0 ###LEFT-WALL### 2 11 0 ###LEFT-WALL### 31 interrater 0 ###LEFT-WALL### 41 . 1 the 2 11 2 11 9 consistency 2 11 31 interrater 3 - 9 consistency 4 item 6 demonstrated 5 sbs 6 demonstrated 6 demonstrated 9 consistency 7 good 9 consistency 8 internal 9 consistency 9 consistency 11 α 9 consistency 17 rater 9 consistency 29 , 10 ( 11 α 11 α 13 0.762 11 α 14 ) 15 , 17 rater 16 intrarater 17 rater 17 rater 18 reliability 17 rater 24 = 17 rater 28 ) 18 reliability 20 icc 18 reliability 24 = 19 ( 20 icc 20 icc 22 3,1 20 icc 23 ) 21 ( 22 3,1 22 3,1 23 ) 24 = 26 to 25 0.96 26 to 26 to 27 0.99 31 interrater 32 reliability 32 reliability 34 icc 33 ( 34 icc 34 icc 38 )(= 34 icc 40 ) 35 ( 38 )(= 36 2,1 38 )(= 38 )(= 39 0.87 38 )(= 40 ) on the basis of analysis of 156 scores , construct and concurrent validity were established . 0 ###LEFT-WALL### 1 on 0 ###LEFT-WALL### 14 were 0 ###LEFT-WALL### 16 . 1 on 3 basis 1 on 14 were 2 the 3 basis 3 basis 4 of 4 of 5 analysis 5 analysis 6 of 6 of 7 156 8 scores 9 , 9 , 10 construct 9 , 11 and 11 and 13 validity 11 and 14 were 12 concurrent 13 validity 14 were 15 established the sbs appears to meet the criteria required to make it a useful tool . 0 ###LEFT-WALL### 2 sbs 0 ###LEFT-WALL### 3 appears 0 ###LEFT-WALL### 15 . 1 the 2 sbs 2 sbs 3 appears 3 appears 4 to 3 appears 5 meet 4 to 5 meet 5 meet 7 criteria 6 the 7 criteria 7 criteria 8 required 8 required 9 to 8 required 10 make 9 to 10 make 10 make 11 it 10 make 14 tool 12 a 14 tool 13 useful 14 tool the sbs can be used to assess sitting balance in frail individuals who are primarily nonambulatory who might exhibit floor effects for traditionally used balance measures . 0 ###LEFT-WALL### 4 be 0 ###LEFT-WALL### 27 . 1 the 2 sbs 2 sbs 3 can 3 can 4 be 4 be 5 used 5 used 6 to 5 used 7 assess 6 to 7 assess 7 assess 9 balance 7 assess 10 in 7 assess 22 for 8 sitting 9 balance 10 in 12 individuals 11 frail 12 individuals 12 individuals 13 who 12 individuals 14 are 13 who 14 are 14 are 15 primarily 14 are 16 nonambulatory 16 nonambulatory 17 who 16 nonambulatory 18 might 17 who 18 might 18 might 19 exhibit 19 exhibit 21 effects 20 floor 21 effects 22 for 26 measures 23 traditionally 24 used 24 used 25 balance 25 balance 26 measures the sbs is the first attempt to assess lower balance abilities . 0 ###LEFT-WALL### 2 sbs 0 ###LEFT-WALL### 3 is 0 ###LEFT-WALL### 12 . 1 the 2 sbs 2 sbs 3 is 3 is 6 attempt 4 the 6 attempt 5 first 6 attempt 6 attempt 7 to 6 attempt 8 assess 7 to 8 assess 8 assess 11 abilities 9 lower 10 balance 10 balance 11 abilities further assessment of the tool 's validity with larger [and] varied samples is necessary . 0 ###LEFT-WALL### 2 assessment 0 ###LEFT-WALL### 13 is 0 ###LEFT-WALL### 15 . 1 further 2 assessment 2 assessment 3 of 2 assessment 13 is 3 of 7 validity 4 the 5 tool 5 tool 6 's 6 's 7 validity 7 validity 8 with 8 with 12 samples 9 larger 12 samples 11 varied 12 samples 13 is 14 necessary objective : the stroop ( stroop , 1935 ) is a frequently used neuropsychological test , with poor performance typically interpreted as indicative of disinhibition and frontal lobe damage . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 2 : 4 stroop 2 : 10 is 3 the 4 stroop 4 stroop 6 stroop 4 stroop 10 is 5 ( 6 stroop 6 stroop 8 1935 6 stroop 9 ) 7 , 8 1935 8 1935 9 ) 10 is 15 test 11 a 15 test 12 frequently 13 used 13 used 15 test 14 neuropsychological 15 test 15 test 17 with 16 , 17 with 17 with 26 and 17 with 30 . 18 poor 19 performance 19 performance 21 interpreted 19 performance 24 of 19 performance 26 and 20 typically 21 interpreted 21 interpreted 23 indicative 22 as 23 indicative 24 of 25 disinhibition 26 and 29 damage 27 frontal 28 lobe 28 lobe 29 damage this study tested those interpretations by examining relationships between stroop performance , behavioral disinhibition , and frontal lobe atrophy . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 tested 0 ###LEFT-WALL### 20 . 1 this 2 study 2 study 3 tested 3 tested 5 interpretations 3 tested 6 by 4 those 5 interpretations 6 by 7 examining 7 examining 8 relationships 7 examining 9 between 9 between 16 and 10 stroop 11 performance 11 performance 12 , 12 , 14 disinhibition 12 , 16 and 13 behavioral 14 disinhibition 15 , 16 and 16 and 19 atrophy 17 frontal 18 lobe 18 lobe 19 atrophy method : participants were 112 patients with mild cognitive impairment or dementia , recruited through ucsf 's memory and aging center . 0 ###LEFT-WALL### 1 method 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 22 . 2 : 3 participants 2 : 13 , 3 participants 13 , 4 were 6 patients 4 were 13 , 5 112 6 patients 6 patients 7 with 7 with 11 or 8 mild 10 impairment 9 cognitive 10 impairment 10 impairment 11 or 11 or 12 dementia 13 , 14 recruited 13 , 15 through 15 through 19 and 16 ucsf 17 's 17 's 18 memory 18 memory 19 and 19 and 21 center 20 aging 21 center participants received comprehensive dementia evaluations including structural mri , neuropsychological testing , and informant interviews . 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 16 . 1 participants 2 received 2 received 5 evaluations 3 comprehensive 5 evaluations 4 dementia 5 evaluations 5 evaluations 6 including 5 evaluations 9 , 6 including 8 mri 7 structural 8 mri 9 , 11 testing 9 , 13 and 10 neuropsychological 11 testing 12 , 13 and 13 and 15 interviews 14 informant 15 interviews freesurfer , a semiautomated parcellation program , was used to analyze 1.5 t mri scans . 0 ###LEFT-WALL### 1 freesurfer 0 ###LEFT-WALL### 9 used 0 ###LEFT-WALL### 16 . 1 freesurfer 6 program 1 freesurfer 8 was 2 , 6 program 3 a 6 program 4 semiautomated 5 parcellation 5 parcellation 6 program 6 program 7 , 8 was 9 used 9 used 10 to 9 used 11 analyze 10 to 11 analyze 11 analyze 14 mri 11 analyze 15 scans 12 1.5 13 t 13 t 14 mri 14 mri 15 scans behavioral disinhibition was measured using the neuropsychiatric inventory ( cummings , 1997 [;] cummings et al . , 1994 ) disinhibition scale . 0 ###LEFT-WALL### 1 behavioral 0 ###LEFT-WALL### 4 measured 0 ###LEFT-WALL### 23 . 1 behavioral 2 disinhibition 1 behavioral 3 was 1 behavioral 4 measured 2 disinhibition 3 was 4 measured 5 using 4 measured 22 scale 5 using 8 inventory 6 the 8 inventory 7 neuropsychiatric 8 inventory 8 inventory 10 cummings 8 inventory 16 al 8 inventory 19 1994 9 ( 10 cummings 10 cummings 11 , 11 , 16 al 12 1997 14 cummings 14 cummings 16 al 15 et 16 al 16 al 17 . 16 al 18 , 18 , 19 1994 19 1994 20 ) 21 disinhibition 22 scale the sample ( n = 112 [ )(mean age was 65.40 ( [sd] = 8.60 [ )(years , education was 16.64 ( sd = 2.54 [ )(years , and mini - mental state examination ( mmse ; folstein et al . , 1975 ) was 26.63 ( [sd] = 3.32 ) . 0 ###LEFT-WALL### 2 sample 0 ###LEFT-WALL### 10 was 0 ###LEFT-WALL### 18 , 0 ###LEFT-WALL### 52 . 1 the 2 sample 2 sample 5 = 2 sample 10 was 3 ( 5 = 4 n 5 = 5 = 9 age 6 112 8 )(mean 8 )(mean 9 age 10 was 11 65.40 11 65.40 17 )(years 12 ( 17 )(years 14 = 15 8.60 15 8.60 17 )(years 17 )(years 18 , 18 , 19 education 18 , 20 was 18 , 37 ; 19 education 20 was 20 was 21 16.64 21 16.64 34 examination 22 ( 34 examination 23 sd 34 examination 24 = 25 2.54 25 2.54 27 )(years 27 )(years 29 and 28 , 29 and 29 and 30 mini 29 and 31 - 29 and 34 examination 32 mental 34 examination 33 state 34 examination 34 examination 36 mmse 34 examination 37 ; 35 ( 36 mmse 36 mmse 37 ; 37 ; 40 al 37 ; 45 was 38 folstein 40 al 39 et 40 al 40 al 41 . 40 al 43 1975 40 al 45 was 42 , 43 1975 43 1975 44 ) 45 was 46 26.63 46 26.63 50 3.32 47 ( 50 3.32 49 = 50 3.32 50 3.32 51 ) hierarchical linear regressions were used for data analysis . 0 ###LEFT-WALL### 3 regressions 0 ###LEFT-WALL### 5 used 0 ###LEFT-WALL### 9 . 1 hierarchical 3 regressions 2 linear 3 regressions 3 regressions 4 were 4 were 5 used 5 used 6 for 6 for 8 analysis 7 data 8 analysis results : controlling for age , mmse , and color naming , stroop performance was not significantly associated with disinhibition ( [β] = 0.01 , δr² = 0.01 , p = [.] 29 ) . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 13 stroop 2 : 27 = 2 : 35 . 3 controlling 4 for 3 controlling 11 naming 3 controlling 12 , 3 controlling 13 stroop 4 for 9 and 5 age 6 , 6 , 7 mmse 6 , 9 and 8 , 9 and 9 and 10 color 13 stroop 18 associated 13 stroop 27 = 14 performance 15 was 15 was 16 not 16 not 17 significantly 17 significantly 18 associated 18 associated 19 with 18 associated 26 δr² 19 with 20 disinhibition 20 disinhibition 24 0.01 21 ( 24 0.01 23 = 24 0.01 24 0.01 25 , 27 = 28 0.01 28 0.01 31 = 29 , 31 = 30 p 31 = 31 = 33 29 31 = 34 ) hierarchical regressions controlling for age , mmse , color naming , intracranial volume , and temporal and parietal lobes , examined whether left or right hemisphere regions predict stroop performance . 0 ###LEFT-WALL### 2 regressions 0 ###LEFT-WALL### 21 examined 0 ###LEFT-WALL### 31 . 1 hierarchical 2 regressions 2 regressions 3 controlling 2 regressions 15 and 2 regressions 21 examined 3 controlling 4 for 3 controlling 10 naming 4 for 5 age 5 age 7 mmse 6 , 7 mmse 7 mmse 8 , 9 color 10 naming 11 , 15 and 12 intracranial 13 volume 13 volume 15 and 14 , 15 and 15 and 19 lobes 15 and 20 , 16 temporal 17 and 17 and 18 parietal 17 and 19 lobes 21 examined 22 whether 22 whether 24 or 22 whether 28 predict 23 left 24 or 24 or 27 regions 24 or 28 predict 25 right 26 hemisphere 26 hemisphere 27 regions 28 predict 30 performance 29 stroop 30 performance bilaterally , parietal lobe atrophy best predicted poorer stroop ( left : β = 0.0004 , δr² = 0.02 , p = [.] 002 ; right : β = 0.0004 , δr² = 0.02 , p = [.] 002 ) . 0 ###LEFT-WALL### 5 atrophy 0 ###LEFT-WALL### 7 predicted 0 ###LEFT-WALL### 12 : 1 bilaterally 2 , 1 bilaterally 5 atrophy 3 parietal 4 lobe 4 lobe 5 atrophy 5 atrophy 7 predicted 6 best 7 predicted 7 predicted 9 stroop 7 predicted 11 left 8 poorer 9 stroop 10 ( 11 left 11 left 12 : 12 : 13 β 12 : 14 = 12 : 16 , 12 : 27 : 13 β 14 = 14 = 15 0.0004 16 , 17 δr² 16 , 18 = 16 , 25 ; 17 δr² 18 = 18 = 19 0.02 19 0.02 22 = 20 , 22 = 21 p 22 = 22 = 24 002 22 = 25 ; 25 ; 26 right 27 : 28 β 27 : 29 = 27 : 31 , 27 : 32 δr² 27 : 41 . 28 β 29 = 29 = 30 0.0004 31 , 32 δr² 32 δr² 34 0.02 33 = 34 0.02 34 0.02 37 = 35 , 37 = 36 p 37 = 37 = 39 002 37 = 40 ) of frontal regions , only dorsolateral prefrontal cortex atrophy predicted poorer stroop ( [β] = 0.001 , δr² = 0.01 , [p] = [.] 03 ) [;] left and right anterior cingulate cortex atrophy predicted better stroop ( left : β = - 0.003 , [δr²] = 0.01 , p = [.] 02 [;] right : β = - 0.004 , [δr²] = 0.01 , p = [.] 02 ) . 0 ###LEFT-WALL### 5 only 0 ###LEFT-WALL### 10 predicted 1 of 3 regions 1 of 4 , 1 of 5 only 2 frontal 3 regions 5 only 9 atrophy 6 dorsolateral 8 cortex 7 prefrontal 8 cortex 8 cortex 9 atrophy 9 atrophy 10 predicted 10 predicted 18 δr² 11 poorer 18 δr² 12 stroop 16 0.001 12 stroop 18 δr² 13 ( 16 0.001 15 = 16 0.001 16 0.001 17 , 18 δr² 20 0.01 18 δr² 29 and 19 = 20 0.01 20 0.01 25 03 20 0.01 29 and 21 , 25 03 23 = 25 03 25 03 26 ) 28 left 29 and 29 and 30 right 29 and 36 better 29 and 40 : 30 right 34 atrophy 31 anterior 33 cortex 32 cingulate 33 cortex 33 cortex 34 atrophy 34 atrophy 35 predicted 37 stroop 39 left 37 stroop 40 : 38 ( 39 left 40 : 51 = 41 β 42 = 42 = 44 0.003 43 - 44 0.003 44 0.003 48 0.01 45 , 48 0.01 47 = 48 0.01 48 0.01 49 , 49 , 51 = 50 p 51 = 51 = 53 02 53 02 55 right 53 02 60 0.004 55 right 56 : 56 : 57 β 56 : 58 = 57 β 58 = 59 - 60 0.004 60 0.004 64 0.01 60 0.004 71 . 61 , 64 0.01 63 = 64 0.01 64 0.01 67 = 64 0.01 70 ) 65 , 67 = 66 p 67 = 67 = 69 02 conclusion : these findings suggest stroop performance is a poor measure of behavioral disinhibition and frontal lobe atrophy even among a relatively high - risk population . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 27 . 2 : 8 is 3 these 4 findings 4 findings 5 suggest 5 suggest 7 performance 5 suggest 8 is 6 stroop 7 performance 8 is 11 measure 9 a 10 poor 9 a 11 measure 10 poor 11 measure 11 measure 12 of 11 measure 19 even 12 of 15 and 13 behavioral 14 disinhibition 14 disinhibition 15 and 15 and 18 atrophy 16 frontal 17 lobe 17 lobe 18 atrophy 19 even 20 among 20 among 26 population 21 a 22 relatively 21 a 26 population 22 relatively 23 high 23 high 24 - 23 high 26 population 25 risk 26 population objective : older driver research has mostly focused on identifying that small proportion of older drivers who are unsafe . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 2 : 5 research 2 : 8 focused 2 : 20 . 3 older 4 driver 4 driver 5 research 5 research 6 has 6 has 8 focused 7 mostly 8 focused 8 focused 9 on 9 on 10 identifying 10 identifying 13 proportion 11 that 12 small 12 small 13 proportion 13 proportion 14 of 14 of 16 drivers 15 older 16 drivers 16 drivers 17 who 16 drivers 18 are 17 who 18 are 18 are 19 unsafe little is known about how normal cognitive changes in aging affect driving in the wider population of adults who drive regularly . 0 ###LEFT-WALL### 1 little 0 ###LEFT-WALL### 3 known 0 ###LEFT-WALL### 22 . 1 little 2 is 2 is 3 known 3 known 4 about 3 known 13 in 4 about 5 how 5 how 8 changes 5 how 11 affect 6 normal 8 changes 7 cognitive 8 changes 8 changes 9 in 8 changes 11 affect 9 in 10 aging 11 affect 12 driving 13 in 16 population 14 the 16 population 15 wider 16 population 16 population 17 of 17 of 18 adults 18 adults 19 who 18 adults 20 drive 19 who 20 drive 20 drive 21 regularly we evaluated the association of cognitive function [and] age with driving errors . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 evaluated 0 ###LEFT-WALL### 13 . 1 we 2 evaluated 2 evaluated 4 association 2 evaluated 10 with 3 the 4 association 4 association 5 of 5 of 9 age 6 cognitive 7 function 7 function 9 age 10 with 11 driving 11 driving 12 errors method : a sample of 266 drivers aged 70 to 88 years were assessed on abilities that decline in normal aging ( visual attention , processing speed , inhibition , reaction time , task switching [ )(and the ufov® , which is a validated screening instrument for older drivers . 0 ###LEFT-WALL### 1 method 0 ###LEFT-WALL### 2 : 1 method 2 : 2 : 4 sample 2 : 19 in 3 a 4 sample 4 sample 5 of 4 sample 7 drivers 4 sample 8 aged 4 sample 14 assessed 5 of 6 266 7 drivers 8 aged 8 aged 10 to 9 70 10 to 10 to 11 88 11 88 12 years 12 years 13 were 14 assessed 15 on 15 on 16 abilities 16 abilities 17 that 16 abilities 18 decline 17 that 18 decline 19 in 21 aging 20 normal 21 aging 21 aging 24 attention 21 aging 26 processing 21 aging 37 )(and 22 ( 24 attention 23 visual 24 attention 24 attention 25 , 25 , 26 processing 26 processing 27 speed 26 processing 33 , 27 speed 29 inhibition 27 speed 32 time 28 , 29 inhibition 29 inhibition 30 , 30 , 32 time 31 reaction 32 time 32 time 33 , 33 , 37 )(and 34 task 35 switching 35 switching 37 )(and 37 )(and 39 ufov® 37 )(and 40 , 37 )(and 41 which 37 )(and 42 is 37 )(and 47 for 37 )(and 50 . 38 the 39 ufov® 41 which 42 is 42 is 46 instrument 43 a 46 instrument 44 validated 46 instrument 45 screening 46 instrument 47 for 49 drivers 48 older 49 drivers participants completed an [on] [-] road driving test . 0 ###LEFT-WALL### 1 participants 0 ###LEFT-WALL### 2 completed 0 ###LEFT-WALL### 9 . 1 participants 2 completed 2 completed 8 test 3 an 8 test 6 road 7 driving 7 driving 8 test generalized linear models were used to estimate the associations of cognitive factors with specific driving errors and number of errors in self [-] directed [and] instructor navigated conditions . 0 ###LEFT-WALL### 3 models 0 ###LEFT-WALL### 5 used 0 ###LEFT-WALL### 29 . 1 generalized 3 models 2 linear 3 models 3 models 4 were 4 were 5 used 5 used 6 to 5 used 13 with 6 to 7 estimate 7 estimate 9 associations 8 the 9 associations 9 associations 10 of 10 of 12 factors 11 cognitive 12 factors 13 with 17 and 14 specific 16 errors 15 driving 16 errors 16 errors 17 and 17 and 18 number 17 and 19 of 19 of 20 errors 20 errors 21 in 21 in 28 conditions 22 self 24 directed 24 directed 28 conditions 26 instructor 27 navigated 27 navigated 28 conditions results : all error types increased with chronological age . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 10 . 1 results 2 : 2 : 5 types 3 all 5 types 4 error 5 types 5 types 6 increased 6 increased 7 with 7 with 9 age 8 chronological 9 age reaction time was not associated with driving errors in multivariate analyses . 0 ###LEFT-WALL### 2 time 0 ###LEFT-WALL### 3 was 0 ###LEFT-WALL### 12 . 1 reaction 2 time 2 time 3 was 3 was 4 not 3 was 6 with 4 not 5 associated 6 with 7 driving 7 driving 8 errors 7 driving 9 in 9 in 11 analyses 10 multivariate 11 analyses a cognitive factor measuring speeded selective attention and switching was uniquely associated with the most errors types . 0 ###LEFT-WALL### 3 factor 0 ###LEFT-WALL### 17 types 0 ###LEFT-WALL### 18 . 1 a 2 cognitive 1 a 3 factor 2 cognitive 3 factor 3 factor 4 measuring 3 factor 10 was 3 factor 12 associated 3 factor 17 types 4 measuring 8 and 4 measuring 10 was 5 speeded 7 attention 5 speeded 8 and 6 selective 7 attention 8 and 9 switching 10 was 11 uniquely 12 associated 13 with 13 with 16 errors 14 the 15 most 15 most 16 errors the ufov® predicted blind - spot errors and errors on dual carriageways . 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 13 . 1 the 7 errors 2 ufov® 3 predicted 3 predicted 6 spot 4 blind 5 - 4 blind 6 spot 6 spot 7 errors 7 errors 8 and 8 and 9 errors 8 and 10 on 10 on 12 carriageways 11 dual 12 carriageways after adjusting for age , education , and gender , the cognitive factors explained 7 % of variance in the total number of errors in the instructor - navigated condition and 4 % [of] variance in the self - navigated condition . 0 ###LEFT-WALL### 13 factors 0 ###LEFT-WALL### 14 explained 0 ###LEFT-WALL### 42 . 1 after 2 adjusting 1 after 10 , 1 after 13 factors 2 adjusting 3 for 3 for 8 and 4 age 5 , 5 , 6 education 5 , 8 and 7 , 8 and 8 and 9 gender 8 and 10 , 11 the 13 factors 12 cognitive 13 factors 13 factors 14 explained 14 explained 16 % 14 explained 40 navigated 15 7 16 % 16 % 17 of 16 % 19 in 16 % 40 navigated 17 of 18 variance 19 in 24 errors 20 the 22 number 21 total 22 number 22 number 23 of 22 number 24 errors 23 of 24 errors 24 errors 25 in 24 errors 31 and 25 in 27 instructor 26 the 27 instructor 28 - 31 and 29 navigated 30 condition 30 condition 31 and 31 and 35 variance 31 and 39 - 32 4 33 % 33 % 35 variance 35 variance 36 in 36 in 38 self 37 the 38 self 40 navigated 41 condition conclusion : we conclude that among older drivers , errors increase with age and [are] associated with speeded selective attention , particularly when that requires attending to the stimuli in the periphery of the visual field , task switching , errors inhibiting responses , and visual discrimination . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 48 . 2 : 3 we 2 : 4 conclude 2 : 9 , 2 : 40 , 3 we 4 conclude 4 conclude 5 that 4 conclude 6 among 6 among 8 drivers 7 older 8 drivers 9 , 10 errors 9 , 14 and 10 errors 14 and 11 increase 12 with 11 increase 14 and 12 with 13 age 14 and 16 associated 14 and 17 with 14 and 23 when 14 and 39 switching 17 with 20 attention 18 speeded 20 attention 19 selective 20 attention 21 , 22 particularly 21 , 23 when 23 when 24 that 23 when 25 requires 23 when 37 , 24 that 25 requires 25 requires 26 attending 25 requires 36 field 26 attending 27 to 26 attending 30 in 27 to 29 stimuli 28 the 29 stimuli 30 in 32 periphery 31 the 32 periphery 32 periphery 33 of 33 of 35 visual 34 the 35 visual 38 task 39 switching 40 , 45 and 41 errors 42 inhibiting 41 errors 45 and 42 inhibiting 43 responses 44 , 45 and 45 and 47 discrimination 46 visual 47 discrimination these abilities should be the target of cognitive training . 0 ###LEFT-WALL### 2 abilities 0 ###LEFT-WALL### 4 be 0 ###LEFT-WALL### 10 . 1 these 2 abilities 2 abilities 3 should 3 should 4 be 4 be 6 target 5 the 6 target 6 target 7 of 7 of 9 training 8 cognitive 9 training objective : both [the] prevalence and incidence of hiv infection among older adults are on the rise . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 2 : 6 and 2 : 14 are 2 : 18 . 3 both 6 and 5 prevalence 6 and 6 and 7 incidence 6 and 8 of 6 and 14 are 8 of 10 infection 9 hiv 10 infection 10 infection 11 among 11 among 13 adults 12 older 13 adults 14 are 15 on 15 on 17 rise 16 the 17 rise older adults are at increased risk of hiv - associated neurocognitive disorders , which have historically been characterized as an inconsistent or " spotty " pattern of deficits . 0 ###LEFT-WALL### 2 adults 0 ###LEFT-WALL### 3 are 0 ###LEFT-WALL### 13 , 0 ###LEFT-WALL### 29 . 1 older 2 adults 2 adults 3 are 3 are 4 at 4 at 6 risk 5 increased 6 risk 6 risk 7 of 6 risk 12 disorders 7 of 8 hiv 9 - 12 disorders 10 associated 12 disorders 11 neurocognitive 12 disorders 12 disorders 13 , 13 , 14 which 13 , 18 characterized 14 which 15 have 15 have 17 been 16 historically 17 been 17 been 18 characterized 18 characterized 19 as 19 as 26 pattern 20 an 26 pattern 21 inconsistent 22 or 22 or 23 " 22 or 24 spotty 22 or 26 pattern 24 spotty 25 " 26 pattern 27 of 27 of 28 deficits dispersion is a form of intraindividual variability ( iiv ) that is defined as within [-] person variability in performance across domains and has been associated with poorer neurocognitive functioning and incipient decline among healthy older adults . 0 ###LEFT-WALL### 1 dispersion 0 ###LEFT-WALL### 23 and 0 ###LEFT-WALL### 38 . 1 dispersion 23 and 2 is 4 form 2 is 23 and 3 a 4 form 4 form 5 of 4 form 11 that 4 form 12 is 5 of 7 variability 6 intraindividual 7 variability 7 variability 9 iiv 8 ( 9 iiv 9 iiv 10 ) 11 that 12 is 12 is 13 defined 13 defined 14 as 13 defined 19 in 14 as 15 within 15 within 18 variability 17 person 18 variability 19 in 20 performance 20 performance 21 across 21 across 22 domains 23 and 24 has 24 has 25 been 25 been 26 associated 26 associated 27 with 27 with 31 and 28 poorer 30 functioning 29 neurocognitive 30 functioning 30 functioning 31 and 31 and 33 decline 31 and 34 among 32 incipient 33 decline 34 among 37 adults 35 healthy 37 adults 36 older 37 adults to our knowledge , no studies have yet examined [dispersion] in [an] aging hiv - infected sample . 0 ###LEFT-WALL### 6 studies 0 ###LEFT-WALL### 9 examined 0 ###LEFT-WALL### 15 - 1 to 3 knowledge 1 to 4 , 1 to 6 studies 2 our 3 knowledge 5 no 6 studies 6 studies 7 have 7 have 9 examined 8 yet 9 examined 9 examined 11 in 9 examined 14 hiv 11 in 13 aging 15 - 17 sample 15 - 18 . 16 infected 17 sample method : for the current study we examined the hypothesis that age and hiv infection have synergistic effects on [dispersion] across a battery of clinical and experimental cognitive tasks . 0 ###LEFT-WALL### 1 method 0 ###LEFT-WALL### 2 : 2 : 7 we 2 : 8 examined 2 : 30 . 3 for 6 study 3 for 7 we 4 the 6 study 5 current 6 study 7 we 8 examined 8 examined 10 hypothesis 8 examined 21 across 9 the 10 hypothesis 10 hypothesis 11 that 10 hypothesis 19 on 11 that 13 and 11 that 16 have 12 age 13 and 13 and 15 infection 13 and 16 have 14 hiv 15 infection 16 have 18 effects 16 have 19 on 17 synergistic 18 effects 21 across 23 battery 22 a 23 battery 23 battery 24 of 24 of 29 tasks 25 clinical 26 and 26 and 27 experimental 26 and 29 tasks 28 cognitive 29 tasks our well - characterized sample comprised 126 hiv - seropositive individuals ( hiv+ ) and 40 hiv - seronegative comparison individuals ( hiv - ) [,] all [of] [whom] were administered a comprehensive neuropsychological battery . 0 ###LEFT-WALL### 2 well 0 ###LEFT-WALL### 3 - 0 ###LEFT-WALL### 36 . 1 our 2 well 3 - 8 hiv 3 - 15 and 4 characterized 8 hiv 5 sample 6 comprised 6 comprised 8 hiv 7 126 8 hiv 8 hiv 11 individuals 9 - 11 individuals 10 seropositive 11 individuals 11 individuals 13 hiv+ 11 individuals 14 ) 12 ( 13 hiv+ 13 hiv+ 14 ) 15 and 16 40 15 and 31 administered 16 40 17 hiv 16 40 30 were 16 40 31 administered 17 hiv 21 individuals 17 hiv 30 were 18 - 21 individuals 19 seronegative 20 comparison 20 comparison 21 individuals 21 individuals 23 hiv 21 individuals 25 ) 22 ( 23 hiv 23 hiv 24 - 27 all 30 were 31 administered 35 battery 32 a 33 comprehensive 32 a 35 battery 33 comprehensive 35 battery 34 neuropsychological 35 battery results : consistent with our hypothesis , an age by hiv serostatus interaction was observed , with the older hiv+ group demonstrating a higher level of dispersion relative to older hiv - and younger hiv+ individuals , even when potentially confounding demographic and medical factors were controlled . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 7 , 1 results 2 : 2 : 3 consistent 3 consistent 4 with 4 with 6 hypothesis 5 our 6 hypothesis 7 , 9 age 7 , 15 observed 8 an 9 age 9 age 10 by 9 age 14 was 10 by 13 interaction 11 hiv 13 interaction 12 serostatus 13 interaction 14 was 15 observed 15 observed 17 with 15 observed 39 when 16 , 17 with 17 with 21 group 17 with 37 , 18 the 21 group 19 older 20 hiv+ 20 hiv+ 21 group 21 group 22 demonstrating 21 group 26 of 22 demonstrating 25 level 23 a 25 level 24 higher 25 level 26 of 36 individuals 27 dispersion 35 hiv+ 28 relative 29 to 28 relative 33 and 29 to 31 hiv 30 older 31 hiv 32 - 33 and 33 and 34 younger 33 and 35 hiv+ 35 hiv+ 36 individuals 37 , 38 even 37 , 39 when 39 when 41 confounding 39 when 47 controlled 39 when 48 . 40 potentially 41 confounding 41 confounding 45 factors 41 confounding 46 were 42 demographic 43 and 43 and 44 medical 43 and 45 factors 46 were 47 controlled 47 controlled 48 . conclusion : our results demonstrate that older hiv+ adults produce greater dispersion , or intraindividual variability in performance across a range of tests , which may be reflective of cognitive dyscontrol to which this population is vulnerable , perhaps driven by the combined effects of aging and hiv infection on prefrontostriatal systems . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 4 results 2 : 5 demonstrate 2 : 24 , 2 : 53 . 3 our 4 results 4 results 5 demonstrate 5 demonstrate 16 variability 5 demonstrate 17 in 6 that 12 dispersion 7 older 8 hiv+ 8 hiv+ 9 adults 9 adults 12 dispersion 10 produce 12 dispersion 11 greater 12 dispersion 12 dispersion 14 or 13 , 14 or 14 or 15 intraindividual 14 or 16 variability 17 in 18 performance 18 performance 19 across 18 performance 22 of 19 across 21 range 20 a 21 range 22 of 23 tests 24 , 25 which 24 , 27 be 25 which 26 may 26 may 27 be 27 be 49 infection 27 be 50 on 28 reflective 29 of 28 reflective 41 by 28 reflective 47 and 29 of 31 dyscontrol 30 cognitive 31 dyscontrol 31 dyscontrol 32 to 31 dyscontrol 40 driven 32 to 33 which 32 to 35 population 32 to 36 is 34 this 35 population 35 population 36 is 36 is 37 vulnerable 38 , 39 perhaps 38 , 40 driven 39 perhaps 40 driven 41 by 44 effects 42 the 44 effects 43 combined 44 effects 44 effects 45 of 45 of 46 aging 47 and 48 hiv 47 and 49 infection 50 on 52 systems 51 prefrontostriatal 52 systems the present study aimed at modeling individual differences in a verbal learning task by means of a latent structured growth curve approach based on an exponential function that yielded 3 parameters : initial recall , learning rate , and asymptotic performance . 0 ###LEFT-WALL### 3 study 0 ###LEFT-WALL### 32 : 0 ###LEFT-WALL### 42 . 1 the 3 study 2 present 3 study 3 study 4 aimed 3 study 5 at 3 study 14 by 3 study 32 : 5 at 6 modeling 6 modeling 8 differences 6 modeling 9 in 7 individual 8 differences 9 in 13 task 10 a 11 verbal 10 a 13 task 11 verbal 13 task 12 learning 13 task 14 by 15 means 15 means 16 of 15 means 23 based 16 of 22 approach 17 a 18 latent 17 a 22 approach 18 latent 20 growth 19 structured 20 growth 20 growth 21 curve 21 curve 22 approach 23 based 24 on 24 on 27 function 25 an 26 exponential 25 an 27 function 26 exponential 27 function 27 function 28 that 27 function 29 yielded 28 that 29 yielded 29 yielded 31 parameters 30 3 31 parameters 32 : 39 and 33 initial 34 recall 34 recall 35 , 35 , 37 rate 35 , 39 and 36 learning 37 rate 38 , 39 and 39 and 41 performance 40 asymptotic 41 performance three cognitive variables - speed of information processing , verbal knowledge , working memory - and the participant 's age were included in the model in order to explain individual differences in the learning parameters . 0 ###LEFT-WALL### 3 variables 0 ###LEFT-WALL### 4 - 1 three 3 variables 2 cognitive 3 variables 4 - 16 and 4 - 22 included 4 - 36 . 5 speed 6 of 5 speed 16 and 6 of 8 processing 7 information 8 processing 8 processing 11 knowledge 8 processing 13 working 9 , 11 knowledge 10 verbal 11 knowledge 11 knowledge 12 , 12 , 13 working 13 working 14 memory 13 working 15 - 16 and 20 age 16 and 21 were 17 the 18 participant 18 participant 19 's 19 's 20 age 21 were 22 included 22 included 23 in 22 included 26 in 22 included 32 in 23 in 25 model 24 the 25 model 26 in 27 order 27 order 28 to 27 order 29 explain 28 to 29 explain 29 explain 31 differences 30 individual 31 differences 32 in 35 parameters 33 the 35 parameters 34 learning 35 parameters the data come from the second wave of the zurich longitudinal study on cognitive aging ( [d] [.] zimprich , martin , et al . , 2008 ) comprising 334 participants ranging in age from 66 to 81 years ( m = 74.43 , sd = 4.41 ) . 0 ###LEFT-WALL### 2 data 0 ###LEFT-WALL### 3 come 0 ###LEFT-WALL### 49 . 1 the 2 data 2 data 3 come 3 come 4 from 3 come 13 on 4 from 7 wave 5 the 7 wave 6 second 7 wave 7 wave 8 of 8 of 12 study 9 the 12 study 10 zurich 11 longitudinal 11 longitudinal 12 study 13 on 15 aging 14 cognitive 15 aging 15 aging 31 participants 16 ( 31 participants 19 zimprich 24 al 19 zimprich 31 participants 20 , 24 al 21 martin 24 al 22 , 24 al 23 et 24 al 24 al 25 . 24 al 27 2008 24 al 28 ) 26 , 27 2008 27 2008 28 ) 29 comprising 31 participants 30 334 31 participants 31 participants 32 ranging 31 participants 48 ) 32 ranging 33 in 32 ranging 47 4.41 33 in 34 age 34 age 35 from 34 age 45 sd 34 age 46 = 35 from 39 years 36 66 37 to 37 to 38 81 37 to 39 years 39 years 42 = 40 ( 42 = 41 m 42 = 42 = 43 74.43 42 = 44 , 45 sd 46 = among the logistic , the gompertz , and the hyperbolic function , the exponential function described the data best . 0 ###LEFT-WALL### 15 function 0 ###LEFT-WALL### 16 described 0 ###LEFT-WALL### 20 . 1 among 8 and 1 among 12 , 1 among 15 function 2 the 3 logistic 3 logistic 4 , 4 , 6 gompertz 4 , 8 and 5 the 6 gompertz 7 , 8 and 8 and 11 function 9 the 11 function 10 hyperbolic 11 function 13 the 15 function 14 exponential 15 function 15 function 16 described 16 described 18 data 16 described 19 best 17 the 18 data reliable individual differences were found in all 3 learning parameters . 0 ###LEFT-WALL### 3 differences 0 ###LEFT-WALL### 5 found 0 ###LEFT-WALL### 11 . 1 reliable 3 differences 2 individual 3 differences 3 differences 4 were 4 were 5 found 5 found 6 in 6 in 8 3 7 all 8 3 8 3 9 learning 9 learning 10 parameters the cognitive predictor variables affected the verbal learning parameters differentially : all 3 predictors affected positively initial recall , the asymptotic performance increased with better working memory and faster processing speed , and the learning rate was positively associated with verbal knowledge only . 0 ###LEFT-WALL### 4 variables 0 ###LEFT-WALL### 5 affected 0 ###LEFT-WALL### 11 : 0 ###LEFT-WALL### 44 . 1 the 4 variables 2 cognitive 3 predictor 3 predictor 4 variables 4 variables 5 affected 5 affected 9 parameters 5 affected 10 differentially 6 the 9 parameters 7 verbal 9 parameters 8 learning 9 parameters 11 : 14 predictors 11 : 17 initial 11 : 19 , 11 : 33 and 12 all 13 3 13 3 14 predictors 14 predictors 15 affected 14 predictors 17 initial 15 affected 16 positively 17 initial 18 recall 19 , 28 and 20 the 22 performance 21 asymptotic 22 performance 22 performance 23 increased 22 performance 24 with 22 performance 28 and 24 with 26 working 25 better 26 working 26 working 27 memory 28 and 31 speed 28 and 32 , 29 faster 31 speed 30 processing 31 speed 32 , 33 and 33 and 36 rate 33 and 39 associated 34 the 36 rate 35 learning 36 rate 36 rate 37 was 37 was 39 associated 38 positively 39 associated 39 associated 40 with 39 associated 43 only 40 with 42 knowledge 41 verbal 42 knowledge age did not affect the learning parameters but correlated negatively with working memory and processing speed . 0 ###LEFT-WALL### 1 age 0 ###LEFT-WALL### 8 but 0 ###LEFT-WALL### 17 . 1 age 2 did 2 did 3 not 2 did 8 but 4 affect 7 parameters 4 affect 8 but 5 the 7 parameters 6 learning 7 parameters 8 but 9 correlated 9 correlated 10 negatively 9 correlated 11 with 11 with 14 and 12 working 13 memory 13 memory 14 and 14 and 16 speed 15 processing 16 speed the finding of large and reliable individual differences in learning is seen as evidence that the potential for positive change , or plasticity in adulthood is maintained and that it is worthwhile to enhance the determinants of learning or learning itself . 0 ###LEFT-WALL### 2 finding 0 ###LEFT-WALL### 34 enhance 0 ###LEFT-WALL### 42 . 1 the 2 finding 2 finding 3 of 2 finding 9 in 2 finding 11 is 3 of 8 differences 4 large 5 and 5 and 6 reliable 5 and 8 differences 7 individual 8 differences 9 in 10 learning 11 is 12 seen 12 seen 13 as 13 as 14 evidence 14 evidence 28 and 15 that 17 potential 15 that 27 maintained 15 that 28 and 16 the 17 potential 17 potential 18 for 17 potential 24 in 17 potential 26 is 18 for 22 or 19 positive 20 change 20 change 22 or 21 , 22 or 22 or 23 plasticity 24 in 25 adulthood 26 is 27 maintained 28 and 29 that 29 that 30 it 29 that 31 is 30 it 31 is 31 is 32 worthwhile 32 worthwhile 33 to 32 worthwhile 34 enhance 33 to 34 enhance 34 enhance 39 or 34 enhance 41 itself 35 the 36 determinants 36 determinants 37 of 36 determinants 39 or 37 of 38 learning 39 or 40 learning part 2 of this review concerns the application of melatonin ( [mt] [ )(to the treatment of aged patients with cardiovascular diseases and other pathology with reference to its genoprotective and anticarcinogenic action . 0 ###LEFT-WALL### 1 part 0 ###LEFT-WALL### 6 concerns 1 part 2 2 1 part 3 of 1 part 6 concerns 3 of 5 review 4 this 5 review 6 concerns 8 application 7 the 8 application 8 application 9 of 8 application 14 )(to 9 of 10 melatonin 11 ( 14 )(to 14 )(to 23 and 14 )(to 34 . 15 the 16 treatment 16 treatment 17 of 16 treatment 20 with 16 treatment 23 and 17 of 19 patients 18 aged 19 patients 20 with 22 diseases 21 cardiovascular 22 diseases 23 and 25 pathology 23 and 26 with 23 and 28 to 24 other 25 pathology 26 with 27 reference 28 to 33 action 29 its 33 action 30 genoprotective 31 and 31 and 32 anticarcinogenic 31 and 33 action effects of [mt] on the cardiovascular system are underlain by its antioxidative , vasodilating , and sedative activities , the ability to regulate the heart rate and inhibit platelet aggregation . 0 ###LEFT-WALL### 1 effects 0 ###LEFT-WALL### 9 underlain 1 effects 2 of 1 effects 8 are 2 of 4 on 4 on 7 system 5 the 7 system 6 cardiovascular 7 system 8 are 9 underlain 9 underlain 10 by 10 by 16 and 11 its 14 vasodilating 12 antioxidative 13 , 12 antioxidative 14 vasodilating 14 vasodilating 16 and 15 , 16 and 16 and 18 activities 16 and 21 ability 17 sedative 18 activities 19 , 21 ability 20 the 21 ability 21 ability 22 to 21 ability 27 and 21 ability 31 . 22 to 27 and 23 regulate 26 rate 23 regulate 27 and 24 the 26 rate 25 heart 26 rate 27 and 28 inhibit 28 inhibit 30 aggregation 29 platelet 30 aggregation certain authors report negative correlation [between] [mt] production and blood cholesterol level . 0 ###LEFT-WALL### 2 authors 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 13 . 1 certain 2 authors 2 authors 9 and 3 report 8 production 3 report 9 and 4 negative 8 production 5 correlation 8 production 9 and 10 blood 9 and 12 level 10 blood 11 cholesterol [mt] [was] [shown] to protect [from] cardiac lesions associated with ischemia and reperfusion . 0 ###LEFT-WALL### 4 to 0 ###LEFT-WALL### 5 protect 0 ###LEFT-WALL### 14 . 4 to 5 protect 5 protect 8 lesions 7 cardiac 8 lesions 8 lesions 9 associated 9 associated 10 with 10 with 12 and 11 ischemia 12 and 12 and 13 reperfusion [mt] inhibits carcinogenesis and is active at systemic , tissue , cellular and subcellular levels . 0 ###LEFT-WALL### 4 and 0 ###LEFT-WALL### 16 . 2 inhibits 3 carcinogenesis 2 inhibits 4 and 4 and 5 is 5 is 15 levels 6 active 7 at 6 active 11 , 7 at 10 tissue 8 systemic 9 , 8 systemic 10 tissue 11 , 12 cellular 11 , 13 and 13 and 14 subcellular 13 and 15 levels at the systemic level , [mt] decreases hormonal production , stimulates immune activity , and prevents the development [of] metabolic syndrome . 0 ###LEFT-WALL### 10 , 0 ###LEFT-WALL### 22 . 1 at 4 level 1 at 5 , 1 at 10 , 2 the 4 level 3 systemic 4 level 7 decreases 9 production 7 decreases 10 , 8 hormonal 9 production 10 , 15 and 11 stimulates 13 activity 11 stimulates 15 and 12 immune 13 activity 14 , 15 and 15 and 16 prevents 16 prevents 21 syndrome 17 the 21 syndrome 18 development 21 syndrome 20 metabolic 21 syndrome it inhibits [cell] [proliferation] and promotes apoptosis of tumour cells but suppresses it the nervous tissue . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 5 and 0 ###LEFT-WALL### 17 . 1 it 5 and 2 inhibits 5 and 5 and 11 but 5 and 16 tissue 6 promotes 7 apoptosis 6 promotes 11 but 7 apoptosis 8 of 8 of 10 cells 9 tumour 10 cells 11 but 12 suppresses 12 suppresses 13 it 14 the 16 tissue 15 nervous 16 tissue [mt] [activates] telomerase . 0 ###LEFT-WALL### 3 telomerase 0 ###LEFT-WALL### 4 . it decreases expression of oncogens and interferes with the action of mutagens and clastogens at the genetic level . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 6 and 0 ###LEFT-WALL### 19 . 1 it 6 and 2 decreases 3 expression 2 decreases 6 and 3 expression 4 of 4 of 5 oncogens 6 and 7 interferes 6 and 8 with 8 with 10 action 9 the 10 action 10 action 11 of 11 of 13 and 12 mutagens 13 and 13 and 14 clastogens 13 and 15 at 15 at 18 level 16 the 18 level 17 genetic 18 level extensive studies of [mt] protective action in nervous diseases are underway with special reference to spinal cord , brain , neuron and glial cell lesions ; experimental cerebral stroke , parkinson ['s] and alzheimer 's diseases . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 10 are 0 ###LEFT-WALL### 26 ; 0 ###LEFT-WALL### 37 . 1 extensive 2 studies 2 studies 3 of 2 studies 10 are 3 of 6 action 5 protective 6 action 6 action 7 in 7 in 9 diseases 8 nervous 9 diseases 10 are 11 underway 11 underway 12 with 11 underway 15 to 12 with 14 reference 13 special 14 reference 15 to 22 and 16 spinal 17 cord 17 cord 18 , 18 , 19 brain 18 , 20 , 20 , 21 neuron 20 , 22 and 22 and 25 lesions 23 glial 24 cell 24 cell 25 lesions 26 ; 29 stroke 26 ; 30 , 27 experimental 29 stroke 28 cerebral 29 stroke 30 , 36 diseases 31 parkinson 33 and 33 and 34 alzheimer 34 alzheimer 35 's 35 's 36 diseases similar studies concern the role of [mt] in the protection against ionizing radiation , the development of renal pathology , and ophthalmology ( glaucoma , cataract ) . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 3 concern 0 ###LEFT-WALL### 28 . 1 similar 2 studies 2 studies 3 concern 3 concern 5 role 3 concern 11 against 4 the 5 role 5 role 6 of 6 of 8 in 8 in 10 protection 9 the 10 protection 11 against 12 ionizing 12 ionizing 13 radiation 13 radiation 21 and 14 , 21 and 15 the 16 development 16 development 17 of 16 development 21 and 17 of 19 pathology 18 renal 19 pathology 20 , 21 and 21 and 26 cataract 21 and 27 ) 22 ophthalmology 24 glaucoma 22 ophthalmology 25 , 22 ophthalmology 26 cataract 23 ( 24 glaucoma 24 glaucoma 25 , [mt] is [shown] [to] influence practically all organ systems by inhibiting mutagenesis and maintaining correlation between circadian rhythms of different biological processes throughout human evolution . 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 26 . 2 is 5 influence 2 is 6 practically 2 is 9 systems 7 all 9 systems 8 organ 9 systems 9 systems 10 by 10 by 11 inhibiting 11 inhibiting 13 and 11 inhibiting 16 between 11 inhibiting 23 throughout 12 mutagenesis 13 and 13 and 15 correlation 14 maintaining 15 correlation 16 between 18 rhythms 17 circadian 18 rhythms 18 rhythms 19 of 19 of 22 processes 20 different 22 processes 21 biological 22 processes 23 throughout 25 evolution 24 human 25 evolution none [in] today 's society , ageing is a phenomenon which is as natural as it is complex . 0 ###LEFT-WALL### 1 none 0 ###LEFT-WALL### 4 's 0 ###LEFT-WALL### 6 , 0 ###LEFT-WALL### 19 . 1 none 3 today 1 none 4 's 4 's 5 society 6 , 7 ageing 6 , 8 is 7 ageing 8 is 8 is 10 phenomenon 9 a 10 phenomenon 10 phenomenon 11 which 10 phenomenon 12 is 11 which 12 is 12 is 14 natural 13 as 14 natural 14 natural 15 as 15 as 16 it 15 as 17 is 15 as 18 complex 16 it 17 is paradoxically , it is a sign of life . 0 ###LEFT-WALL### 3 it 0 ###LEFT-WALL### 4 is 0 ###LEFT-WALL### 9 . 1 paradoxically 2 , 1 paradoxically 3 it 3 it 4 is 4 is 6 sign 5 a 6 sign 6 sign 7 of 7 of 8 life elderly people must be treated with dignity and spared from the prejudices which currently surround old age . 0 ###LEFT-WALL### 2 people 0 ###LEFT-WALL### 4 be 0 ###LEFT-WALL### 18 . 1 elderly 2 people 2 people 3 must 3 must 4 be 4 be 8 and 5 treated 6 with 5 treated 8 and 6 with 7 dignity 8 and 9 spared 8 and 10 from 10 from 12 prejudices 11 the 12 prejudices 12 prejudices 13 which 12 prejudices 15 surround 13 which 15 surround 14 currently 15 surround 15 surround 17 age 16 old 17 age the impact of parkinson 's disease on quality of life may vary depending on age [at] [onset] . 0 ###LEFT-WALL### 2 impact 0 ###LEFT-WALL### 12 vary 0 ###LEFT-WALL### 18 . 1 the 2 impact 2 impact 3 of 2 impact 11 may 3 of 6 disease 4 parkinson 5 's 5 's 6 disease 6 disease 7 on 7 on 8 quality 8 quality 9 of 9 of 10 life 11 may 12 vary 12 vary 13 depending 12 vary 14 on 14 on 15 age we investigated the effect of age at onset on quality of life in a large parkinson 's disease population ( n = 426 [ )(using a disease - specific rating scale ( pdq - 39 ) and [with] careful adjustment for confounding and intermediary factors . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 investigated 1 we 2 investigated 2 investigated 4 effect 2 investigated 13 in 3 the 4 effect 4 effect 5 of 4 effect 7 at 4 effect 11 of 5 of 6 age 7 at 8 onset 8 onset 9 on 9 on 10 quality 11 of 12 life 13 in 19 population 14 a 16 parkinson 15 large 16 parkinson 16 parkinson 17 's 17 's 19 population 18 disease 19 population 19 population 22 = 20 ( 22 = 21 n 22 = 22 = 23 426 23 426 25 )(using 25 )(using 27 disease 26 a 27 disease 27 disease 37 and 28 - 37 and 29 specific 30 rating 29 specific 37 and 30 rating 31 scale 30 rating 34 - 32 ( 34 - 33 pdq 34 - 34 - 35 39 34 - 36 ) 37 and 40 adjustment 37 and 41 for 37 and 46 . 39 careful 40 adjustment 41 for 45 factors 42 confounding 43 and 43 and 44 intermediary 43 and 45 factors we also explored the relationship between depression and excessive daytime sleepiness by age [at] [onset] and compared this with the general population . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 16 and 0 ###LEFT-WALL### 23 . 1 we 16 and 2 also 3 explored 3 explored 5 relationship 3 explored 6 between 3 explored 16 and 4 the 5 relationship 6 between 8 and 7 depression 8 and 8 and 10 daytime 8 and 11 sleepiness 9 excessive 10 daytime 11 sleepiness 12 by 12 by 13 age 16 and 17 compared 17 compared 18 this 17 compared 19 with 19 with 22 population 20 the 22 population 21 general 22 population [younger] [onset] was [also] a risk factor for poor emotional well [-] being independent of depression status . 0 ###LEFT-WALL### 3 was 0 ###LEFT-WALL### 18 . 3 was 7 factor 5 a 7 factor 6 risk 7 factor 7 factor 8 for 8 for 11 well 9 poor 11 well 10 emotional 11 well 11 well 13 being 11 well 15 of 13 being 14 independent 15 of 17 status 16 depression 17 status risk of depression and excessive daytime sleepiness were elevated in patients with parkinson 's disease compared with controls ( odds [ratio] , 2.99 ; 95 % confidence interval , 1.93 - 4.65 ; p < . 001 ; [and] odds ratio , 3.84 ; 95 % confidence interval , 2.56 - 5.75 ; p < [.] 001 , respectively ) , with similar findings seen in both early - and late - onset groups . 0 ###LEFT-WALL### 1 risk 0 ###LEFT-WALL### 16 compared 0 ###LEFT-WALL### 22 , 0 ###LEFT-WALL### 36 . 1 risk 2 of 1 risk 8 were 2 of 4 and 3 depression 4 and 4 and 7 sleepiness 5 excessive 7 sleepiness 6 daytime 7 sleepiness 8 were 9 elevated 9 elevated 10 in 9 elevated 12 with 10 in 11 patients 12 with 15 disease 12 with 16 compared 13 parkinson 14 's 14 's 15 disease 16 compared 17 with 17 with 18 controls 18 controls 20 odds 19 ( 20 odds 20 odds 22 , 22 , 23 2.99 22 , 24 ; 24 ; 28 interval 24 ; 29 , 25 95 27 confidence 26 % 27 confidence 27 confidence 28 interval 29 , 30 1.93 29 , 31 - 29 , 33 ; 30 1.93 31 - 31 - 32 4.65 33 ; 34 p 33 ; 35 < 34 p 35 < 36 . 37 001 36 . 38 ; 38 ; 41 ratio 38 ; 42 , 40 odds 41 ratio 42 , 43 3.84 42 , 44 ; 44 ; 48 interval 44 ; 49 , 45 95 48 interval 46 % 48 interval 47 confidence 48 interval 49 , 50 2.56 49 , 51 - 49 , 53 ; 50 2.56 51 - 51 - 52 5.75 53 ; 54 p 53 ; 55 < 53 ; 72 - 54 p 55 < 55 < 57 001 55 < 59 respectively 55 < 62 with 58 , 59 respectively 59 respectively 60 ) 61 , 62 with 62 with 64 findings 62 with 70 and 62 with 72 - 63 similar 64 findings 64 findings 65 seen 64 findings 66 in 66 in 67 both 68 early 70 and 69 - 70 and 70 and 71 late 72 - 74 groups 72 - 75 . 73 onset 74 groups our study highlights the need for accurate diagnosis and treatment of depression in younger - onset patients in order to improve quality of life . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 highlights 0 ###LEFT-WALL### 25 . 1 our 2 study 2 study 3 highlights 3 highlights 5 need 3 highlights 6 for 3 highlights 13 in 3 highlights 18 in 4 the 5 need 6 for 9 and 7 accurate 8 diagnosis 8 diagnosis 9 and 9 and 10 treatment 9 and 11 of 11 of 12 depression 13 in 17 patients 14 younger 15 - 14 younger 16 onset 16 onset 17 patients 18 in 19 order 19 order 20 to 19 order 21 improve 20 to 21 improve 21 improve 22 quality 22 quality 23 of 23 of 24 life estrogen is implicated as playing an important role in aging and tumorigenesis of estrogen responsive tissues ; however the mechanisms underlying the mitogenic actions of estrogen are not fully understood . 0 ###LEFT-WALL### 1 estrogen 0 ###LEFT-WALL### 17 ; 0 ###LEFT-WALL### 31 . 1 estrogen 2 is 2 is 3 implicated 3 implicated 4 as 4 as 16 tissues 5 playing 16 tissues 6 an 7 important 6 an 8 role 7 important 8 role 8 role 9 in 8 role 11 and 9 in 10 aging 11 and 12 tumorigenesis 11 and 13 of 11 and 16 tissues 13 of 14 estrogen 15 responsive 16 tissues 17 ; 20 mechanisms 17 ; 30 understood 18 however 20 mechanisms 19 the 20 mechanisms 20 mechanisms 21 underlying 20 mechanisms 27 are 21 underlying 24 actions 22 the 24 actions 23 mitogenic 24 actions 24 actions 25 of 25 of 26 estrogen 27 are 28 not 27 are 30 understood 29 fully 30 understood here we report that estrogen deficiency in mice caused by targeted disruption of the aromatase gene results in a significant inhibition of telomerase maintenance of telomeres in mouse ovaries in a tissue - specific manner . 0 ###LEFT-WALL### 2 we 0 ###LEFT-WALL### 3 report 0 ###LEFT-WALL### 33 - 1 here 2 we 2 we 3 report 3 report 4 that 4 that 6 deficiency 4 that 17 results 5 estrogen 6 deficiency 6 deficiency 7 in 6 deficiency 9 caused 6 deficiency 13 of 6 deficiency 17 results 7 in 8 mice 9 caused 10 by 10 by 12 disruption 11 targeted 12 disruption 13 of 16 gene 14 the 16 gene 15 aromatase 16 gene 17 results 18 in 17 results 27 in 17 results 30 in 18 in 21 inhibition 19 a 21 inhibition 20 significant 21 inhibition 21 inhibition 22 of 22 of 24 maintenance 23 telomerase 24 maintenance 24 maintenance 25 of 25 of 26 telomeres 27 in 29 ovaries 28 mouse 29 ovaries 30 in 32 tissue 31 a 32 tissue 33 - 35 manner 33 - 36 . 34 specific 35 manner the inhibition entails a significant shortening of telomeres and [compromised] proliferation in the follicular granulosa cell compartment [of] ovary . 0 ###LEFT-WALL### 2 inhibition 0 ###LEFT-WALL### 3 entails 0 ###LEFT-WALL### 20 . 1 the 2 inhibition 2 inhibition 3 entails 3 entails 19 ovary 4 a 5 significant 4 a 19 ovary 5 significant 6 shortening 6 shortening 7 of 6 shortening 9 and 7 of 8 telomeres 9 and 11 proliferation 9 and 12 in 9 and 19 ovary 12 in 15 granulosa 13 the 15 granulosa 14 follicular 15 granulosa 16 cell 19 ovary 17 compartment 19 ovary gene expression analysis showed decreased levels of proto - oncogene [c] - myc and the telomerase catalytic subunit , telomerase reverse transcriptase ( tert ) , in response to estrogen deficiency . 0 ###LEFT-WALL### 3 analysis 0 ###LEFT-WALL### 4 showed 0 ###LEFT-WALL### 32 . 1 gene 3 analysis 2 expression 3 analysis 3 analysis 4 showed 4 showed 6 levels 4 showed 18 subunit 4 showed 29 to 5 decreased 6 levels 6 levels 7 of 7 of 14 and 8 proto 10 oncogene 8 proto 13 myc 9 - 10 oncogene 10 oncogene 12 - 13 myc 14 and 14 and 16 telomerase 15 the 16 telomerase 17 catalytic 18 subunit 18 subunit 22 transcriptase 19 , 22 transcriptase 20 telomerase 22 transcriptase 21 reverse 22 transcriptase 22 transcriptase 24 tert 22 transcriptase 26 , 23 ( 24 tert 24 tert 25 ) 27 in 28 response 28 response 29 to 29 to 31 deficiency 30 estrogen 31 deficiency estrogen replacement therapy led to increases in tert gene expression , telomerase activity , telomere length and ovarian tissue growth , thereby reinstating ovary development to normal in four weeks . 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 31 . 1 estrogen 3 therapy 2 replacement 3 therapy 3 therapy 4 led 3 therapy 11 , 4 led 5 to 5 to 6 increases 6 increases 7 in 7 in 10 expression 8 tert 10 expression 9 gene 10 expression 11 , 13 activity 11 , 14 , 12 telomerase 13 activity 14 , 16 length 14 , 17 and 15 telomere 16 length 17 and 20 growth 17 and 21 , 17 and 23 reinstating 18 ovarian 19 tissue 19 tissue 20 growth 22 thereby 23 reinstating 23 reinstating 25 development 23 reinstating 27 normal 23 reinstating 28 in 24 ovary 25 development 26 to 27 normal 28 in 30 weeks 29 four 30 weeks our data demonstrate for the first time that telomere maintenance is the primary mechanism mediating the mitogenic effect of estrogen on ovarian granulosa cell proliferation [by] upregulating the genes of [c] [-] myc and tert in vivo . 0 ###LEFT-WALL### 2 data 0 ###LEFT-WALL### 3 demonstrate 0 ###LEFT-WALL### 38 . 1 our 2 data 2 data 3 demonstrate 3 demonstrate 4 for 3 demonstrate 29 genes 3 demonstrate 37 vivo 4 for 7 time 5 the 7 time 6 first 7 time 7 time 10 maintenance 7 time 11 is 8 that 9 telomere 9 telomere 10 maintenance 10 maintenance 11 is 11 is 14 mechanism 12 the 14 mechanism 13 primary 14 mechanism 14 mechanism 15 mediating 14 mechanism 19 of 14 mechanism 21 on 15 mediating 18 effect 16 the 18 effect 17 mitogenic 18 effect 19 of 20 estrogen 21 on 27 upregulating 22 ovarian 23 granulosa 23 granulosa 27 upregulating 24 cell 27 upregulating 25 proliferation 27 upregulating 28 the 29 genes 29 genes 30 of 30 of 35 tert 33 myc 34 and 34 and 35 tert 36 in 37 vivo estrogen deficiency or [over] - activity may cause ovarian tissue aging or tumorigenesis , respectively , through estrogen regulation of telomere remodeling . 0 ###LEFT-WALL### 2 deficiency 0 ###LEFT-WALL### 3 or 0 ###LEFT-WALL### 23 . 1 estrogen 2 deficiency 3 or 5 - 3 or 8 cause 5 - 6 activity 6 activity 7 may 7 may 8 cause 8 cause 12 or 8 cause 15 respectively 8 cause 17 through 9 ovarian 10 tissue 10 tissue 11 aging 10 tissue 12 or 12 or 13 tumorigenesis 14 , 15 respectively 15 respectively 16 , 17 through 19 regulation 18 estrogen 19 regulation 19 regulation 20 of 20 of 22 remodeling 21 telomere 22 remodeling background and objective : food insecurity negatively impacts hiv disease outcomes in international settings . 0 ###LEFT-WALL### 3 objective 0 ###LEFT-WALL### 4 : 1 background 2 and 2 and 3 objective 4 : 6 insecurity 4 : 8 impacts 4 : 15 . 5 food 6 insecurity 6 insecurity 8 impacts 7 negatively 8 impacts 8 impacts 11 outcomes 8 impacts 12 in 9 hiv 11 outcomes 10 disease 11 outcomes 12 in 14 settings 13 international 14 settings no large scale [u.s] . studies have investigated the association between food insecurity and severity of hiv disease or the mechanism of this possible association . 0 ###LEFT-WALL### 3 scale 0 ###LEFT-WALL### 5 . 1 no 3 scale 2 large 3 scale 5 . 6 studies 5 . 8 investigated 5 . 26 . 6 studies 7 have 7 have 8 investigated 8 investigated 10 association 8 investigated 11 between 9 the 10 association 11 between 19 or 12 food 13 insecurity 13 insecurity 14 and 14 and 15 severity 14 and 16 of 14 and 19 or 16 of 18 disease 17 hiv 18 disease 19 or 21 mechanism 19 or 22 of 20 the 21 mechanism 22 of 25 association 23 this 25 association 24 possible 25 association the objective of this study was to examine the impact of food insecurity on hiv disease outcomes in a large cohort of hiv - infected patients receiving antiretroviral medications . 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 examine 7 to 8 examine 8 examine 10 impact 8 examine 18 in 9 the 10 impact 10 impact 11 of 11 of 13 insecurity 12 food 13 insecurity 13 insecurity 14 on 14 on 17 outcomes 15 hiv 17 outcomes 16 disease 17 outcomes 18 in 21 cohort 19 a 20 large 19 a 21 cohort 20 large 21 cohort 21 cohort 22 of 22 of 23 hiv 23 hiv 26 patients 24 - 26 patients 25 infected 26 patients 26 patients 27 receiving 26 patients 30 . 27 receiving 29 medications 28 antiretroviral 29 medications design : this is a cross - sectional study . 0 ###LEFT-WALL### 1 design 0 ###LEFT-WALL### 2 : 2 : 3 this 2 : 4 is 2 : 7 - 2 : 10 . 3 this 4 is 4 is 6 cross 5 a 6 cross 7 - 9 study 8 sectional 9 study participants and setting : participants were hiv - infected patients enrolled in the veterans aging cohort study between 2002 - 2008 who were receiving antiretroviral medications . 0 ###LEFT-WALL### 3 setting 0 ###LEFT-WALL### 4 : 0 ###LEFT-WALL### 6 were 0 ###LEFT-WALL### 27 . 1 participants 2 and 2 and 3 setting 4 : 5 participants 4 : 6 were 5 participants 6 were 6 were 7 hiv 6 were 21 2008 7 hiv 10 patients 8 - 10 patients 9 infected 10 patients 10 patients 11 enrolled 10 patients 12 in 10 patients 20 - 12 in 17 study 13 the 17 study 14 veterans 15 aging 15 aging 16 cohort 16 cohort 17 study 17 study 18 between 18 between 19 2002 21 2008 22 who 21 2008 23 were 22 who 23 were 23 were 26 medications 24 receiving 26 medications 25 antiretroviral 26 medications main measurements : participants reporting " concern about having enough food for you or your family in the past 30 days " were defined as food insecure . 0 ###LEFT-WALL### 2 measurements 0 ###LEFT-WALL### 3 : 1 main 2 measurements 3 : 14 or 3 : 24 defined 3 : 28 . 4 participants 5 reporting 4 participants 8 about 4 participants 14 or 5 reporting 6 " 5 reporting 7 concern 8 about 9 having 9 having 11 food 9 having 12 for 10 enough 11 food 12 for 13 you 14 or 16 family 14 or 17 in 14 or 23 were 15 your 16 family 17 in 21 days 18 the 21 days 19 past 21 days 20 30 21 days 21 days 22 " 23 were 24 defined 24 defined 25 as 24 defined 27 insecure 25 as 26 food using multivariable logistic regression , we explored the association between food insecurity and both low cd4 counts ( < 200 cells/μl ) [and] unsuppressed hiv - 1 rna ( >500 [copies/ml] ) . 0 ###LEFT-WALL### 6 we 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 26 - 0 ###LEFT-WALL### 33 . 1 using 4 regression 1 using 5 , 1 using 6 we 2 multivariable 3 logistic 3 logistic 4 regression 6 we 13 and 7 explored 9 association 7 explored 13 and 8 the 9 association 9 association 10 between 10 between 12 insecurity 11 food 12 insecurity 13 and 15 low 14 both 15 low 15 low 17 counts 16 cd4 17 counts 17 counts 25 hiv 18 ( 25 hiv 19 < 20 200 20 200 25 hiv 21 cells/μl 22 ) 21 cells/μl 25 hiv 24 unsuppressed 25 hiv 25 hiv 26 - 26 - 28 rna 27 1 28 rna 28 rna 30 >500 29 ( 30 >500 30 >500 32 ) we then performed mediation analysis to examine whether [antiretroviral] [adherence] or body mass index mediates the observed associations . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 performed 0 ###LEFT-WALL### 19 . 1 we 3 performed 2 then 3 performed 3 performed 5 analysis 3 performed 6 to 4 mediation 5 analysis 6 to 7 examine 7 examine 11 or 7 examine 15 mediates 8 whether 11 or 11 or 14 index 11 or 15 mediates 12 body 14 index 13 mass 14 index 15 mediates 18 associations 16 the 18 associations 17 observed 18 associations key results : among 2353 hiv - infected participants receiving antiretroviral medications , 24 % reported food insecurity . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 3 : 0 ###LEFT-WALL### 13 , 0 ###LEFT-WALL### 19 . 1 key 2 results 2 results 3 : 3 : 4 among 4 among 6 hiv 5 2353 6 hiv 6 hiv 9 participants 7 - 9 participants 8 infected 9 participants 9 participants 10 receiving 9 participants 13 , 10 receiving 12 medications 11 antiretroviral 12 medications 13 , 15 % 13 , 16 reported 14 24 15 % 15 % 16 reported 16 reported 18 insecurity 17 food 18 insecurity in adjusted analyses , food insecure participants were more likely to have an unsuppressed hiv - 1 rna ( aor 1.37 , 95 % ci 1.09 , 1.73 ) compared to food secure participants . 0 ###LEFT-WALL### 7 participants 0 ###LEFT-WALL### 8 were 0 ###LEFT-WALL### 35 . 1 in 3 analyses 1 in 4 , 1 in 7 participants 2 adjusted 3 analyses 5 food 7 participants 6 insecure 7 participants 7 participants 8 were 8 were 10 likely 9 more 10 likely 10 likely 11 to 10 likely 12 have 11 to 12 have 12 have 15 hiv 12 have 31 to 13 an 15 hiv 14 unsuppressed 15 hiv 15 hiv 30 compared 16 - 30 compared 17 1 18 rna 18 rna 20 aor 18 rna 28 1.73 18 rna 30 compared 19 ( 20 aor 20 aor 21 1.37 20 aor 25 ci 20 aor 27 , 22 , 25 ci 23 95 25 ci 24 % 25 ci 25 ci 26 1.09 25 ci 27 , 27 , 28 1.73 28 1.73 29 ) 31 to 34 participants 32 food 34 participants 33 secure 34 participants mediation analysis revealed that neither antiretroviral medication adherence nor body mass index contributes to the association between food insecurity and unsuppressed hiv - 1 rna . 0 ###LEFT-WALL### 1 mediation 0 ###LEFT-WALL### 20 and 0 ###LEFT-WALL### 23 - 1 mediation 2 analysis 1 mediation 3 revealed 1 mediation 20 and 2 analysis 3 revealed 3 revealed 9 nor 4 that 8 adherence 5 neither 6 antiretroviral 6 antiretroviral 7 medication 7 medication 8 adherence 8 adherence 9 nor 9 nor 12 index 10 body 11 mass 11 mass 12 index 13 contributes 14 to 13 contributes 20 and 14 to 16 association 15 the 16 association 16 association 17 between 17 between 19 insecurity 18 food 19 insecurity 20 and 21 unsuppressed 21 unsuppressed 22 hiv 23 - 25 rna 23 - 26 . 24 1 25 rna food insecurity was not independently associated with low cd4 counts . 0 ###LEFT-WALL### 2 insecurity 0 ###LEFT-WALL### 6 associated 0 ###LEFT-WALL### 11 . 1 food 2 insecurity 2 insecurity 3 was 3 was 4 not 3 was 6 associated 5 independently 6 associated 6 associated 7 with 7 with 10 counts 8 low 10 counts 9 cd4 10 counts conclusions : among hiv - infected participants receiving antiretroviral medications , food insecurity is associated with unsuppressed [viral] [load] and may render treatment less effective . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 26 . 2 : 13 insecurity 2 : 22 render 3 among 4 hiv 3 among 13 insecurity 4 hiv 7 participants 5 - 7 participants 6 infected 7 participants 7 participants 8 receiving 7 participants 11 , 8 receiving 10 medications 9 antiretroviral 10 medications 12 food 13 insecurity 13 insecurity 14 is 14 is 15 associated 15 associated 16 with 16 with 20 and 17 unsuppressed 20 and 20 and 21 may 21 may 22 render 22 render 23 treatment 22 render 25 effective 24 less 25 effective longitudinal studies are needed to test the potential causal association between food insecurity , lack of virologic suppression , and additional hiv outcomes . 0 ###LEFT-WALL### 2 studies 0 ###LEFT-WALL### 4 needed 0 ###LEFT-WALL### 24 . 1 longitudinal 2 studies 2 studies 3 are 3 are 4 needed 4 needed 5 to 5 to 6 test 6 test 10 association 7 the 10 association 8 potential 10 association 9 causal 10 association 10 association 11 between 11 between 20 and 12 food 13 insecurity 13 insecurity 14 , 14 , 15 lack 14 , 20 and 15 lack 16 of 16 of 18 suppression 17 virologic 18 suppression 19 , 20 and 20 and 23 outcomes 21 additional 23 outcomes 22 hiv 23 outcomes background : comorbidity - a condition that co - [exists] with a primary illness - is common among older persons with heart failure and can complicate the overall management of this population . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 1 background 2 : 2 : 3 comorbidity 3 comorbidity 6 condition 4 - 6 condition 5 a 6 condition 6 condition 7 that 6 condition 33 . 7 that 8 co 7 that 24 and 8 co 11 with 8 co 24 and 9 - 11 with 11 with 13 primary 11 with 14 illness 11 with 15 - 12 a 13 primary 16 is 17 common 16 is 24 and 17 common 18 among 17 common 21 with 18 among 20 persons 19 older 20 persons 21 with 23 failure 22 heart 23 failure 24 and 25 can 25 can 26 complicate 26 complicate 29 management 27 the 29 management 28 overall 29 management 29 management 30 of 30 of 32 population 31 this 32 population objectives : to determine the relationship between advancing age and the prevalence and patterns of comorbidity among older persons with heart failure . 0 ###LEFT-WALL### 1 objectives 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 23 . 2 : 3 to 2 : 4 determine 3 to 4 determine 4 determine 6 relationship 4 determine 7 between 4 determine 17 among 5 the 6 relationship 7 between 13 and 8 advancing 9 age 9 age 10 and 10 and 12 prevalence 10 and 13 and 11 the 12 prevalence 13 and 14 patterns 13 and 15 of 15 of 16 comorbidity 17 among 19 persons 18 older 19 persons 19 persons 20 with 20 with 22 failure 21 heart 22 failure design : retrospective longitudinal cohort study participants : a total of 201,130 medicare beneficiaries with heart failure stratified into three age strata in 2001 : 66 - 75 , 76 - 85 , and 86+ years , [and] followed over 5 years . 0 ###LEFT-WALL### 1 design 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 43 . 2 : 7 participants 2 : 8 : 3 retrospective 5 cohort 4 longitudinal 5 cohort 5 cohort 6 study 6 study 7 participants 8 : 34 and 8 : 39 followed 9 a 10 total 10 total 11 of 10 total 15 with 10 total 18 stratified 10 total 34 and 11 of 14 beneficiaries 12 201,130 14 beneficiaries 13 medicare 14 beneficiaries 15 with 17 failure 16 heart 17 failure 18 stratified 19 into 18 stratified 27 - 18 stratified 31 - 19 into 20 three 20 three 22 strata 20 three 25 : 21 age 22 strata 22 strata 23 in 22 strata 25 : 23 in 24 2001 26 66 27 - 27 - 28 75 29 , 31 - 30 76 31 - 31 - 32 85 31 - 33 , 33 , 34 and 34 and 36 years 34 and 37 , 34 and 39 followed 35 86+ 36 years 39 followed 40 over 40 over 42 years 41 5 42 years results : the median number of comorbidities rose from four ( iqr : 2 - 5 [ )(to five [(] iqr : 4 - 7 ) among the young - old , and from 4 ( iqr [:] 3 - 6 [ )(to 6 ( iqr [:] 5 - 8 ) among the middle - old and oldest [-] old between 2001 and 2006 . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 5 number 2 : 13 : 3 the 5 number 4 median 5 number 5 number 6 of 5 number 8 rose 6 of 7 comorbidities 8 rose 9 from 9 from 10 four 10 four 12 iqr 11 ( 12 iqr 12 iqr 13 : 13 : 14 2 13 : 15 - 14 2 15 - 15 - 21 iqr 16 5 18 )(to 18 )(to 19 five 18 )(to 21 iqr 21 iqr 22 : 22 : 23 4 22 : 33 and 23 4 25 7 24 - 25 7 25 7 26 ) 27 among 31 old 27 among 33 and 28 the 31 old 29 young 30 - 29 young 31 old 32 , 33 and 33 and 34 from 34 from 35 4 35 4 40 - 36 ( 40 - 37 iqr 39 3 37 iqr 40 - 40 - 41 6 41 6 43 )(to 41 6 52 among 43 )(to 44 6 44 6 46 iqr 45 ( 46 iqr 46 iqr 48 5 46 iqr 50 8 46 iqr 51 ) 49 - 50 8 50 8 51 ) 52 among 54 middle 53 the 54 middle 54 middle 60 old 55 - 60 old 56 old 57 and 57 and 58 oldest 57 and 60 old 60 old 63 and 60 old 65 . 61 between 63 and 62 2001 63 and 63 and 64 2006 in 2001 , the majority of concordant conditions were more prevalent among the youngest than oldest beneficiaries ( e.g [.] , [diabetes] 46.2 % vs 26.9 % [;] kidney disease 21.8 [%] vs 18.4 % [ )( [while] the majority of discordant conditions were more prevalent among the oldest - [old] than youngest - old beneficiaries [(] e.g [.] , dementia 39.6 % [vs] 9.9 % [;] hip fracture 9.5 [%] vs 1.9 % [ )( 0 ###LEFT-WALL### 5 majority 0 ###LEFT-WALL### 9 were 1 in 2 2001 1 in 3 , 1 in 5 majority 4 the 5 majority 5 majority 6 of 5 majority 9 were 6 of 8 conditions 7 concordant 8 conditions 9 were 11 prevalent 10 more 11 prevalent 11 prevalent 12 among 12 among 24 % 13 the 14 youngest 13 the 16 oldest 13 the 24 % 15 than 16 oldest 16 oldest 21 , 17 beneficiaries 19 e.g 18 ( 19 e.g 19 e.g 21 , 23 46.2 24 % 24 % 25 vs 25 vs 30 disease 26 26.9 27 % 27 % 29 kidney 29 kidney 30 disease 30 disease 31 21.8 30 disease 33 vs 33 vs 35 % 34 18.4 35 % 35 % 40 majority 35 % 44 were 35 % 46 prevalent 39 the 40 majority 40 majority 41 of 40 majority 44 were 41 of 43 conditions 42 discordant 43 conditions 45 more 46 prevalent 46 prevalent 47 among 47 among 58 e.g 48 the 49 oldest 48 the 53 youngest 48 the 58 e.g 49 oldest 50 - 52 than 53 youngest 53 youngest 54 - 55 old 56 beneficiaries 56 beneficiaries 58 e.g 58 e.g 69 fracture 60 , 69 fracture 61 dementia 69 fracture 62 39.6 63 % 63 % 69 fracture 65 9.9 69 fracture 66 % 69 fracture 68 hip 69 fracture 69 fracture 70 9.5 69 fracture 72 vs 69 fracture 76 )( 72 vs 74 % 73 1.9 74 % discordant conditions increased in prevalence faster among the oldest than youngest beneficiaries ( e.g [.] , dementia 13 % points versus 9 % points ) . 0 ###LEFT-WALL### 2 conditions 0 ###LEFT-WALL### 3 increased 0 ###LEFT-WALL### 26 . 1 discordant 2 conditions 2 conditions 3 increased 3 increased 4 in 4 in 5 prevalence 5 prevalence 6 faster 6 faster 7 among 7 among 12 beneficiaries 8 the 9 oldest 8 the 11 youngest 8 the 12 beneficiaries 10 than 11 youngest 12 beneficiaries 20 points 13 ( 20 points 14 e.g 16 , 14 e.g 17 dementia 17 dementia 20 points 18 13 19 % 19 % 20 points 20 points 21 versus 20 points 25 ) 21 versus 24 points 22 9 24 points 23 % 24 points conclusion : among older medicare beneficiaries with heart failure , there is a higher overall burden of comorbidity and greater prevalence of discordant comorbidity among the oldest old . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 10 , 0 ###LEFT-WALL### 29 . 1 conclusion 2 : 2 : 3 among 2 : 7 with 3 among 6 beneficiaries 4 older 6 beneficiaries 5 medicare 6 beneficiaries 7 with 9 failure 8 heart 9 failure 10 , 11 there 10 , 12 is 11 there 12 is 12 is 21 prevalence 12 is 28 old 13 a 21 prevalence 14 higher 15 overall 15 overall 16 burden 16 burden 17 of 16 burden 19 and 17 of 18 comorbidity 19 and 20 greater 19 and 21 prevalence 21 prevalence 22 of 21 prevalence 25 among 22 of 24 comorbidity 23 discordant 24 comorbidity 25 among 27 oldest 26 the 27 oldest comorbidity prevalence increases over time , with discordant comorbidity increasing at the fastest rate among the oldest old . 0 ###LEFT-WALL### 2 prevalence 0 ###LEFT-WALL### 3 increases 1 comorbidity 2 prevalence 2 prevalence 3 increases 3 increases 4 over 4 over 5 time 5 time 7 with 6 , 7 with 7 with 9 comorbidity 7 with 19 . 8 discordant 9 comorbidity 9 comorbidity 10 increasing 10 increasing 11 at 10 increasing 15 among 11 at 14 rate 12 the 13 fastest 12 the 14 rate 15 among 18 old 16 the 17 oldest 16 the 18 old this comorbidity burden highlights the challenge of effectively treating heart failure while simultaneously managing co - existing and unrelated conditions . 0 ###LEFT-WALL### 3 burden 0 ###LEFT-WALL### 4 highlights 0 ###LEFT-WALL### 21 . 1 this 3 burden 2 comorbidity 3 burden 3 burden 4 highlights 4 highlights 6 challenge 5 the 6 challenge 6 challenge 7 of 7 of 9 treating 8 effectively 9 treating 9 treating 11 failure 9 treating 12 while 10 heart 11 failure 12 while 14 managing 13 simultaneously 14 managing 14 managing 20 conditions 15 co 16 - 15 co 17 existing 17 existing 18 and 18 and 19 unrelated 18 and 20 conditions none inactivation of the rb tumor suppressor and activation of the myc family of oncogenes are frequent events in a large spectrum of human cancers . 0 ###LEFT-WALL### 1 none 0 ###LEFT-WALL### 17 frequent 0 ###LEFT-WALL### 26 . 1 none 8 and 1 none 16 are 1 none 17 frequent 2 inactivation 3 of 2 inactivation 8 and 3 of 7 suppressor 4 the 7 suppressor 5 rb 7 suppressor 6 tumor 7 suppressor 8 and 9 activation 8 and 10 of 8 and 16 are 10 of 13 family 11 the 13 family 12 myc 13 family 13 family 14 of 14 of 15 oncogenes 17 frequent 18 events 17 frequent 19 in 19 in 22 spectrum 20 a 21 large 20 a 22 spectrum 21 large 22 spectrum 22 spectrum 23 of 23 of 25 cancers 24 human 25 cancers loss of rb function and myc activation are thought to control both overlapping and distinct cellular processes during cell cycle progression . 0 ###LEFT-WALL### 4 function 0 ###LEFT-WALL### 5 and 0 ###LEFT-WALL### 22 . 1 loss 2 of 1 loss 4 function 2 of 3 rb 5 and 7 activation 5 and 8 are 6 myc 7 activation 7 activation 8 are 8 are 17 processes 9 thought 10 to 9 thought 14 and 10 to 11 control 11 control 13 overlapping 12 both 13 overlapping 14 and 15 distinct 14 and 17 processes 16 cellular 17 processes 17 processes 18 during 18 during 21 progression 19 cell 21 progression 20 cycle 21 progression however , how these two major cancer genes functionally interact during tumorigenesis is still unclear . 0 ###LEFT-WALL### 3 how 0 ###LEFT-WALL### 13 is 0 ###LEFT-WALL### 16 . 1 however 2 , 1 however 3 how 3 how 8 genes 3 how 10 interact 3 how 13 is 4 these 5 two 5 two 8 genes 6 major 7 cancer 7 cancer 8 genes 8 genes 10 interact 9 functionally 10 interact 10 interact 11 during 11 during 12 tumorigenesis 13 is 14 still 13 is 15 unclear 14 still 15 unclear we found that rb inactivation has minimal effects on the cell cycle , cell death , and differentiation features of liver tumors driven by increased levels of [c] [-] myc . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 found 0 ###LEFT-WALL### 31 . 1 we 2 found 2 found 4 rb 2 found 8 effects 2 found 17 and 3 that 4 rb 4 rb 5 inactivation 4 rb 6 has 5 inactivation 6 has 7 minimal 8 effects 8 effects 9 on 9 on 12 cycle 10 the 12 cycle 11 cell 12 cycle 12 cycle 15 death 13 , 15 death 14 cell 15 death 15 death 16 , 17 and 18 differentiation 17 and 19 features 19 features 20 of 19 features 23 driven 19 features 27 of 20 of 22 tumors 21 liver 22 tumors 23 driven 24 by 24 by 26 levels 25 increased 26 levels 27 of 30 myc however , combined loss of rb and activation of [c] [-] myc led to an increase in polyploidy in mature hepatocytes before the development of tumors . 0 ###LEFT-WALL### 7 and 0 ###LEFT-WALL### 13 led 0 ###LEFT-WALL### 27 . 1 however 2 , 1 however 7 and 3 combined 4 loss 4 loss 5 of 4 loss 7 and 5 of 6 rb 7 and 8 activation 7 and 9 of 7 and 13 led 9 of 12 myc 13 led 14 to 13 led 17 in 13 led 19 in 13 led 22 before 14 to 16 increase 15 an 16 increase 17 in 18 polyploidy 19 in 21 hepatocytes 20 mature 21 hepatocytes 22 before 24 development 23 the 24 development 24 development 25 of 25 of 26 tumors there was a trend for decreased survival in double mutant animals compared to mice developing [c] - myc - induced tumors . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 was 0 ###LEFT-WALL### 19 - 0 ###LEFT-WALL### 22 . 1 there 2 was 2 was 4 trend 3 a 4 trend 4 trend 5 for 4 trend 8 in 4 trend 13 to 4 trend 18 myc 5 for 7 survival 6 decreased 7 survival 8 in 11 animals 9 double 11 animals 10 mutant 11 animals 11 animals 12 compared 13 to 14 mice 14 mice 15 developing 17 - 18 myc 18 myc 19 - 19 - 21 tumors 20 induced 21 tumors thus , loss of rb [function] does not provide a proliferative advantage [to] [c] - myc - expressing hcc cells but the rb and [c] - myc pathways may cooperate to control the polyploidy of mature hepatocytes . 0 ###LEFT-WALL### 3 loss 0 ###LEFT-WALL### 9 provide 0 ###LEFT-WALL### 17 - 0 ###LEFT-WALL### 38 . 1 thus 2 , 1 thus 3 loss 3 loss 4 of 3 loss 7 does 4 of 5 rb 7 does 8 not 7 does 9 provide 9 provide 12 advantage 10 a 11 proliferative 10 a 12 advantage 11 proliferative 12 advantage 12 advantage 16 myc 15 - 16 myc 16 myc 17 - 17 - 20 cells 17 - 21 but 17 - 32 control 18 expressing 20 cells 19 hcc 20 cells 21 but 28 pathways 21 but 30 cooperate 22 the 28 pathways 23 rb 24 and 24 and 27 myc 26 - 27 myc 27 myc 28 pathways 28 pathways 29 may 29 may 30 cooperate 30 cooperate 31 to 31 to 32 control 32 control 34 polyploidy 33 the 34 polyploidy 34 polyploidy 35 of 35 of 37 hepatocytes 36 mature 37 hepatocytes community structure is a universal and significant feature of many complex networks in biology , society , and economics . 0 ###LEFT-WALL### 2 structure 0 ###LEFT-WALL### 3 is 0 ###LEFT-WALL### 20 . 1 community 2 structure 2 structure 3 is 3 is 8 feature 4 a 8 feature 5 universal 6 and 6 and 7 significant 6 and 8 feature 8 feature 9 of 9 of 12 networks 10 many 12 networks 11 complex 12 networks 12 networks 13 in 13 in 18 and 14 biology 15 , 15 , 16 society 15 , 18 and 17 , 18 and 18 and 19 economics community structure has also been revealed in human brain structural and functional networks in previous studies . 0 ###LEFT-WALL### 2 structure 0 ###LEFT-WALL### 6 revealed 0 ###LEFT-WALL### 17 . 1 community 2 structure 2 structure 3 has 3 has 5 been 4 also 5 been 5 been 6 revealed 6 revealed 7 in 7 in 13 networks 8 human 9 brain 9 brain 13 networks 10 structural 11 and 11 and 12 functional 11 and 13 networks 13 networks 14 in 14 in 16 studies 15 previous 16 studies however , communities overlap and share many edges and nodes . 0 ###LEFT-WALL### 3 communities 0 ###LEFT-WALL### 5 and 0 ###LEFT-WALL### 11 . 1 however 2 , 1 however 3 communities 3 communities 5 and 4 overlap 5 and 5 and 6 share 6 share 9 and 7 many 8 edges 8 edges 9 and 9 and 10 nodes uncovering the overlapping community structure of complex networks remains largely unknown in human brain networks . 0 ###LEFT-WALL### 1 uncovering 0 ###LEFT-WALL### 9 remains 0 ###LEFT-WALL### 16 . 1 uncovering 5 structure 1 uncovering 9 remains 2 the 5 structure 3 overlapping 4 community 4 community 5 structure 5 structure 6 of 6 of 8 networks 7 complex 8 networks 9 remains 11 unknown 10 largely 11 unknown 11 unknown 12 in 12 in 15 networks 13 human 14 brain 14 brain 15 networks here , using regional gray matter volume , we investigated the structural brain network among 90 brain regions ( according to a predefined anatomical atlas ) in 462 young , healthy individuals . 0 ###LEFT-WALL### 9 we 0 ###LEFT-WALL### 10 investigated 0 ###LEFT-WALL### 33 . 1 here 2 , 1 here 9 we 2 , 3 using 3 using 7 volume 3 using 8 , 3 using 9 we 4 regional 6 matter 5 gray 6 matter 6 matter 7 volume 9 we 10 investigated 10 investigated 14 network 10 investigated 15 among 10 investigated 21 to 10 investigated 27 in 11 the 14 network 12 structural 13 brain 13 brain 14 network 15 among 18 regions 16 90 18 regions 17 brain 18 regions 19 ( 21 to 20 according 21 to 21 to 25 atlas 21 to 26 ) 22 a 25 atlas 23 predefined 25 atlas 24 anatomical 25 atlas 27 in 32 individuals 28 462 32 individuals 29 young 30 , 29 young 32 individuals 31 healthy 32 individuals overlapped nodes between communities were defined by assuming that nodes ( brain regions ) can belong to more than one community . 0 ###LEFT-WALL### 2 nodes 0 ###LEFT-WALL### 6 defined 0 ###LEFT-WALL### 22 . 1 overlapped 2 nodes 2 nodes 3 between 2 nodes 5 were 3 between 4 communities 5 were 6 defined 6 defined 7 by 7 by 8 assuming 8 assuming 9 that 9 that 10 nodes 9 that 16 belong 10 nodes 13 regions 10 nodes 15 can 11 ( 13 regions 12 brain 13 regions 13 regions 14 ) 15 can 16 belong 16 belong 17 to 17 to 21 community 18 more 19 than 19 than 20 one 20 one 21 community we demonstrated that 90 brain regions were organized into 5 overlapping communities associated with several well - known brain systems , such as the auditory/language , visuospatial , emotion , decision - making , social , control of action , memory/learning , and visual systems . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 demonstrated 0 ###LEFT-WALL### 46 . 1 we 2 demonstrated 2 demonstrated 3 that 3 that 6 regions 3 that 7 were 4 90 6 regions 5 brain 6 regions 6 regions 7 were 7 were 43 and 8 organized 9 into 8 organized 40 , 9 into 12 communities 10 5 12 communities 11 overlapping 12 communities 12 communities 13 associated 13 associated 14 with 14 with 16 well 14 with 37 control 15 several 16 well 16 well 20 systems 17 - 20 systems 18 known 19 brain 19 brain 20 systems 20 systems 23 as 20 systems 34 , 21 , 23 as 22 such 23 as 23 as 31 decision 23 as 34 , 24 the 31 decision 25 auditory/language 29 emotion 25 auditory/language 30 , 25 auditory/language 31 decision 26 , 29 emotion 27 visuospatial 28 , 27 visuospatial 29 emotion 29 emotion 30 , 31 decision 33 making 32 - 33 making 33 making 34 , 35 social 36 , 35 social 37 control 37 control 38 of 38 of 39 action 40 , 41 memory/learning 40 , 43 and 42 , 43 and 43 and 45 systems 44 visual 45 systems the overlapped nodes were mostly involved in an inferior - posterior pattern and were primarily related to auditory and visual perception . 0 ###LEFT-WALL### 3 nodes 0 ###LEFT-WALL### 13 and 0 ###LEFT-WALL### 22 . 1 the 3 nodes 2 overlapped 3 nodes 3 nodes 13 and 4 were 6 involved 4 were 13 and 5 mostly 6 involved 6 involved 7 in 7 in 12 pattern 8 an 9 inferior 8 an 12 pattern 9 inferior 10 - 9 inferior 11 posterior 11 posterior 12 pattern 13 and 14 were 14 were 16 related 15 primarily 16 related 16 related 17 to 17 to 21 perception 18 auditory 19 and 19 and 20 visual 19 and 21 perception the overlapped nodes were mainly attributed to brain regions with higher node degrees and nodal efficiency and played a pivotal role in the flow of information through the structural brain network . 0 ###LEFT-WALL### 3 nodes 0 ###LEFT-WALL### 31 network 0 ###LEFT-WALL### 32 . 1 the 3 nodes 2 overlapped 3 nodes 3 nodes 17 and 3 nodes 31 network 4 were 6 attributed 4 were 17 and 5 mainly 6 attributed 6 attributed 7 to 6 attributed 10 with 7 to 8 brain 8 brain 9 regions 10 with 14 and 11 higher 12 node 12 node 13 degrees 13 degrees 14 and 14 and 16 efficiency 15 nodal 16 efficiency 17 and 18 played 17 and 22 in 18 played 21 role 19 a 20 pivotal 19 a 21 role 20 pivotal 21 role 22 in 24 flow 23 the 24 flow 24 flow 25 of 25 of 26 information 26 information 27 through 27 through 30 brain 28 the 30 brain 29 structural 30 brain our results revealed fuzzy boundaries between communities by identifying overlapped nodes and provided new insights into the understanding of the relationship between the structure and function of the human brain . 0 ###LEFT-WALL### 2 results 0 ###LEFT-WALL### 12 and 0 ###LEFT-WALL### 31 . 1 our 2 results 2 results 12 and 3 revealed 5 boundaries 3 revealed 12 and 4 fuzzy 5 boundaries 5 boundaries 6 between 5 boundaries 8 by 6 between 7 communities 8 by 9 identifying 9 identifying 11 nodes 10 overlapped 11 nodes 12 and 13 provided 13 provided 15 insights 14 new 15 insights 15 insights 16 into 15 insights 19 of 15 insights 27 of 16 into 18 understanding 17 the 18 understanding 19 of 25 and 20 the 21 relationship 21 relationship 22 between 21 relationship 25 and 22 between 24 structure 23 the 24 structure 25 and 26 function 27 of 30 brain 28 the 30 brain 29 human 30 brain this study provides the first report of the overlapping community structure of the structural network of the human brain . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 provides 0 ###LEFT-WALL### 20 . 1 this 2 study 2 study 3 provides 3 provides 6 report 4 the 5 first 4 the 6 report 6 report 7 of 7 of 11 structure 8 the 11 structure 9 overlapping 10 community 10 community 11 structure 11 structure 12 of 12 of 15 network 13 the 15 network 14 structural 15 network 15 network 16 of 16 of 19 brain 17 the 19 brain 18 human 19 brain telomere [function] is essential to maintaining the physical integrity of linear chromosomes and healthy human aging . 0 ###LEFT-WALL### 1 telomere 0 ###LEFT-WALL### 3 is 0 ###LEFT-WALL### 17 . 1 telomere 3 is 3 is 16 aging 4 essential 5 to 4 essential 13 and 5 to 6 maintaining 6 maintaining 9 integrity 7 the 9 integrity 8 physical 9 integrity 9 integrity 10 of 10 of 12 chromosomes 11 linear 12 chromosomes 13 and 14 healthy 13 and 15 human 15 human 16 aging the probability of forming proper telomere structures depends on the length of the telomeric dna tract . 0 ###LEFT-WALL### 2 probability 0 ###LEFT-WALL### 8 depends 0 ###LEFT-WALL### 17 . 1 the 2 probability 2 probability 3 of 2 probability 8 depends 3 of 4 forming 4 forming 7 structures 5 proper 7 structures 6 telomere 7 structures 8 depends 9 on 9 on 11 length 10 the 11 length 11 length 12 of 12 of 16 tract 13 the 16 tract 14 telomeric 16 tract 15 dna 16 tract we attempted to identify common genetic variants associated with log relative telomere length using genome [-] wide genotyping data on 3,554 individuals from the nurses ' health study and the prostate , lung , colorectal , and ovarian cancer screening trial that took part in the national cancer institute cancer genetic markers of susceptibility initiative for breast [and] prostate cancer . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 attempted 0 ###LEFT-WALL### 61 . 1 we 2 attempted 2 attempted 3 to 2 attempted 9 with 2 attempted 13 length 2 attempted 23 from 3 to 4 identify 4 identify 7 variants 5 common 7 variants 6 genetic 7 variants 7 variants 8 associated 9 with 12 telomere 10 log 12 telomere 11 relative 12 telomere 13 length 14 using 14 using 19 data 15 genome 19 data 17 wide 19 data 18 genotyping 19 data 19 data 20 on 20 on 22 individuals 21 3,554 22 individuals 23 from 37 and 24 the 25 nurses 25 nurses 26 ' 26 ' 28 study 27 health 28 study 28 study 29 and 29 and 31 prostate 29 and 32 , 30 the 31 prostate 32 , 33 lung 32 , 34 , 34 , 35 colorectal 34 , 37 and 36 , 37 and 37 and 41 trial 37 and 42 that 37 and 44 part 37 and 53 of 38 ovarian 39 cancer 39 cancer 40 screening 40 screening 41 trial 42 that 44 part 43 took 44 part 44 part 45 in 45 in 52 markers 46 the 52 markers 47 national 48 cancer 48 cancer 49 institute 49 institute 50 cancer 50 cancer 51 genetic 51 genetic 52 markers 53 of 55 initiative 54 susceptibility 55 initiative 55 initiative 56 for 56 for 60 cancer 57 breast 60 cancer 59 prostate 60 cancer after genotyping 64 independent snps selected for replication in additional nurses ' health study and women 's genome health study participants , we did not identify genome [-] wide significant loci [;] however [,] we replicated the inverse association of log relative telomere length with the minor allele variant [[] c []] of rs16847897 at the terc locus [(] per allele β = - 0.03 , p = 0.003 [ )(identified by a previous genome - wide association study . 0 ###LEFT-WALL### 5 snps 0 ###LEFT-WALL### 6 selected 1 after 2 genotyping 1 after 5 snps 3 64 5 snps 4 independent 5 snps 5 snps 6 selected 6 selected 7 for 6 selected 9 in 6 selected 15 and 7 for 8 replication 9 in 13 health 10 additional 11 nurses 11 nurses 12 ' 12 ' 13 health 14 study 15 and 15 and 21 participants 15 and 22 , 15 and 23 we 15 and 26 identify 16 women 17 's 17 's 21 participants 18 genome 19 health 19 health 20 study 20 study 21 participants 23 we 24 did 24 did 25 not 24 did 26 identify 26 identify 31 loci 26 identify 33 however 27 genome 31 loci 29 wide 31 loci 30 significant 31 loci 33 however 35 we 33 however 36 replicated 35 we 36 replicated 36 replicated 39 association 36 replicated 45 with 37 the 39 association 38 inverse 39 association 39 association 40 of 40 of 44 length 41 log 43 telomere 42 relative 43 telomere 43 telomere 44 length 45 with 48 allele 45 with 49 variant 46 the 48 allele 47 minor 48 allele 49 variant 51 c 49 variant 53 of 49 variant 55 at 53 of 54 rs16847897 55 at 57 terc 56 the 57 terc 57 terc 58 locus 57 terc 63 = 57 terc 65 0.03 57 terc 68 = 58 locus 60 per 58 locus 63 = 60 per 62 β 61 allele 62 β 64 - 65 0.03 65 0.03 66 , 67 p 68 = 68 = 69 0.003 69 0.003 71 )(identified 69 0.003 72 by 69 0.003 79 study 72 by 75 genome 73 a 75 genome 74 previous 75 genome 76 - 79 study 77 wide 78 association 78 association 79 study 79 study 80 . we did not find evidence for an association with variants at the obfc1 locus or other loci reported to be associated with telomere length . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 4 find 0 ###LEFT-WALL### 25 . 1 we 2 did 2 did 3 not 2 did 4 find 4 find 5 evidence 4 find 14 locus 4 find 15 or 4 find 19 to 5 evidence 6 for 5 evidence 9 with 6 for 8 association 7 an 8 association 9 with 10 variants 10 variants 11 at 11 at 13 obfc1 12 the 13 obfc1 15 or 17 loci 16 other 17 loci 17 loci 18 reported 19 to 20 be 20 be 21 associated 21 associated 22 with 22 with 24 length 23 telomere 24 length with this sample size we had >80 % power to detect β estimates as small as ±0.10 for snps with minor allele frequencies of ≥0.15 at genome [-] wide significance . 0 ###LEFT-WALL### 5 we 0 ###LEFT-WALL### 6 had 0 ###LEFT-WALL### 31 . 1 with 4 size 1 with 5 we 2 this 4 size 3 sample 4 size 5 we 6 had 6 had 9 power 7 >80 9 power 8 % 9 power 9 power 10 to 9 power 11 detect 10 to 11 detect 11 detect 13 estimates 12 β 13 estimates 13 estimates 15 small 13 estimates 18 for 13 estimates 26 at 14 as 15 small 15 small 16 as 16 as 17 ±0.10 18 for 19 snps 19 snps 20 with 19 snps 24 of 20 with 23 frequencies 21 minor 22 allele 22 allele 23 frequencies 24 of 25 ≥0.15 26 at 30 significance 27 genome 30 significance 29 wide 30 significance however , power is greatly reduced for β estimates smaller than ±0.10 , such as those for variants at the terc locus . 0 ###LEFT-WALL### 3 power 0 ###LEFT-WALL### 6 reduced 1 however 2 , 1 however 3 power 3 power 4 is 4 is 5 greatly 4 is 6 reduced 6 reduced 7 for 7 for 9 estimates 8 β 9 estimates 9 estimates 10 smaller 10 smaller 11 than 11 than 12 ±0.10 12 ±0.10 15 as 13 , 15 as 14 such 15 as 15 as 16 those 15 as 23 . 16 those 17 for 17 for 18 variants 18 variants 19 at 19 at 22 locus 20 the 22 locus 21 terc 22 locus in general , common genetic variants associated with telomere length homeostasis have been difficult to detect . 0 ###LEFT-WALL### 1 in 0 ###LEFT-WALL### 13 been 0 ###LEFT-WALL### 17 . 1 in 6 variants 1 in 13 been 2 general 3 , 2 general 6 variants 4 common 6 variants 5 genetic 6 variants 6 variants 7 associated 7 associated 8 with 8 with 10 length 9 telomere 10 length 11 homeostasis 12 have 12 have 13 been 13 been 14 difficult 14 difficult 15 to 14 difficult 16 detect 15 to 16 detect potential biological and technical issues are discussed . 0 ###LEFT-WALL### 5 issues 0 ###LEFT-WALL### 7 discussed 0 ###LEFT-WALL### 8 . 1 potential 5 issues 2 biological 3 and 3 and 4 technical 3 and 5 issues 5 issues 6 are 6 are 7 discussed epigenetic regulation of gene expression is well known [mechanism] that regulates cellular senescence of cancer cells . 0 ###LEFT-WALL### 2 regulation 0 ###LEFT-WALL### 6 is 0 ###LEFT-WALL### 17 . 1 epigenetic 2 regulation 2 regulation 3 of 2 regulation 6 is 3 of 5 expression 4 gene 5 expression 6 is 7 well 7 well 8 known 7 well 10 that 7 well 11 regulates 10 that 11 regulates 11 regulates 13 senescence 12 cellular 13 senescence 13 senescence 14 of 14 of 16 cells 15 cancer 16 cells here we show that inhibition of dna methyltransferases ( dnmts ) with 5 - azacytidine ( 5 - azac ) or with specific small interfering rna ( sirna ) against dnmt1 and 3b induced the cellular senescence of human umbilical cord blood - derived multipotent stem cells ( hucb - mscs ) and increased p16 ( ink4a ) and p21 ( cip1/waf1 ) expression . 0 ###LEFT-WALL### 2 we 0 ###LEFT-WALL### 3 show 0 ###LEFT-WALL### 32 and 0 ###LEFT-WALL### 65 . 1 here 2 we 2 we 3 show 3 show 4 that 3 show 5 inhibition 3 show 21 or 3 show 30 against 5 inhibition 6 of 6 of 8 methyltransferases 7 dna 8 methyltransferases 8 methyltransferases 10 dnmts 9 ( 10 dnmts 10 dnmts 11 ) 12 with 13 5 12 with 21 or 13 5 15 azacytidine 13 5 19 azac 14 - 15 azacytidine 15 azacytidine 17 5 15 azacytidine 18 - 16 ( 17 5 17 5 18 - 18 - 19 azac 19 azac 20 ) 21 or 22 with 22 with 26 rna 23 specific 26 rna 24 small 26 rna 25 interfering 26 rna 26 rna 28 sirna 27 ( 28 sirna 28 sirna 29 ) 30 against 31 dnmt1 32 and 33 3b 32 and 34 induced 33 3b 34 induced 34 induced 59 and 35 the 37 senescence 36 cellular 37 senescence 37 senescence 38 of 37 senescence 53 and 38 of 42 blood 39 human 41 cord 40 umbilical 41 cord 41 cord 42 blood 42 blood 47 cells 42 blood 51 mscs 43 - 47 cells 44 derived 47 cells 45 multipotent 47 cells 46 stem 47 cells 47 cells 49 hucb 47 cells 50 - 48 ( 49 hucb 49 hucb 50 - 50 - 51 mscs 51 mscs 52 ) 53 and 55 p16 53 and 57 ink4a 53 and 59 and 54 increased 55 p16 56 ( 57 ink4a 57 ink4a 58 ) 59 and 64 expression 60 p21 62 cip1/waf1 60 p21 64 expression 61 ( 62 cip1/waf1 62 cip1/waf1 63 ) dnmt inhibition changed histone marks into the active forms and decreased the methylation of cpg islands in the p16 ( ink4a ) and p21 ( cip1/waf1 ) promoter regions . 0 ###LEFT-WALL### 23 and 0 ###LEFT-WALL### 30 . 1 dnmt 2 inhibition 2 inhibition 10 and 2 inhibition 23 and 3 changed 5 marks 3 changed 6 into 3 changed 10 and 4 histone 5 marks 6 into 9 forms 7 the 9 forms 8 active 9 forms 10 and 11 decreased 10 and 17 in 10 and 19 p16 11 decreased 13 methylation 12 the 13 methylation 13 methylation 14 of 14 of 16 islands 15 cpg 16 islands 18 the 19 p16 19 p16 21 ink4a 20 ( 21 ink4a 21 ink4a 22 ) 23 and 29 regions 24 p21 26 cip1/waf1 24 p21 28 promoter 25 ( 26 cip1/waf1 26 cip1/waf1 27 ) 28 promoter 29 regions enrichment of ezh2 , the key factor that methylates histone h3 lysine 9 and 27 residues , was decreased on the p16 ( ink4a ) and p21 ( cip1/waf1 ) promoter regions . 0 ###LEFT-WALL### 26 and 0 ###LEFT-WALL### 33 . 1 enrichment 2 of 1 enrichment 26 and 2 of 3 ezh2 3 ezh2 7 factor 4 , 7 factor 5 the 7 factor 6 key 7 factor 7 factor 8 that 7 factor 17 , 7 factor 25 ) 8 that 17 , 9 methylates 16 residues 9 methylates 17 , 10 histone 12 lysine 11 h3 12 lysine 12 lysine 14 and 12 lysine 16 residues 13 9 14 and 14 and 15 27 17 , 18 was 18 was 19 decreased 19 decreased 20 on 20 on 22 p16 21 the 22 p16 22 p16 24 ink4a 23 ( 24 ink4a 24 ink4a 25 ) 26 and 32 regions 27 p21 29 cip1/waf1 27 p21 31 promoter 28 ( 29 cip1/waf1 29 cip1/waf1 30 ) 31 promoter 32 regions we found that dnmt inhibition decreased expression levels of polycomb - group [(] pcg ) proteins and increased expression of micrornas ( mirnas ) , which target pcg proteins . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 found 0 ###LEFT-WALL### 25 , 0 ###LEFT-WALL### 30 . 1 we 2 found 2 found 3 that 3 that 5 inhibition 3 that 17 and 4 dnmt 5 inhibition 5 inhibition 17 and 6 decreased 8 levels 6 decreased 17 and 7 expression 8 levels 8 levels 9 of 9 of 16 proteins 10 polycomb 14 pcg 10 polycomb 16 proteins 11 - 14 pcg 12 group 14 pcg 14 pcg 15 ) 17 and 18 increased 18 increased 19 expression 19 expression 20 of 20 of 21 micrornas 21 micrornas 23 mirnas 22 ( 23 mirnas 23 mirnas 24 ) 25 , 26 which 25 , 27 target 26 which 27 target 27 target 29 proteins 28 pcg 29 proteins decreased cpg island methylation and increased levels of active histone marks at genomic regions encoding mirnas were observed after 5 - azac treatment . 0 ###LEFT-WALL### 5 and 0 ###LEFT-WALL### 18 observed 1 decreased 4 methylation 2 cpg 4 methylation 3 island 4 methylation 4 methylation 5 and 5 and 7 levels 5 and 8 of 5 and 15 encoding 5 and 17 were 6 increased 7 levels 8 of 11 marks 9 active 10 histone 10 histone 11 marks 11 marks 12 at 12 at 14 regions 13 genomic 14 regions 15 encoding 16 mirnas 17 were 18 observed 18 observed 19 after 19 after 20 5 20 5 23 treatment 21 - 23 treatment 22 azac 23 treatment 23 treatment 24 . taken together , dnmts have a critical role in regulating the cellular senescence of hucb - mscs through controlling not only the dna methylation status but also active/inactive histone marks at genomic regions of pcg - targeting mirnas and p16 ( ink4a ) and p21 ( cip1/waf1 ) promoter regions . 0 ###LEFT-WALL### 4 dnmts 0 ###LEFT-WALL### 5 have 0 ###LEFT-WALL### 20 not 0 ###LEFT-WALL### 51 . 1 taken 2 together 1 taken 3 , 1 taken 4 dnmts 4 dnmts 5 have 5 have 8 role 5 have 18 through 6 a 7 critical 6 a 8 role 7 critical 8 role 8 role 9 in 8 role 14 of 9 in 10 regulating 10 regulating 13 senescence 11 the 13 senescence 12 cellular 13 senescence 14 of 17 mscs 15 hucb 16 - 15 hucb 17 mscs 18 through 19 controlling 20 not 21 only 20 not 25 status 20 not 30 marks 22 the 25 status 23 dna 24 methylation 24 methylation 25 status 25 status 26 but 25 status 30 marks 26 but 27 also 26 but 29 histone 28 active/inactive 29 histone 30 marks 31 at 30 marks 50 regions 31 at 33 regions 32 genomic 33 regions 33 regions 34 of 34 of 44 and 35 pcg 37 targeting 35 pcg 44 and 36 - 37 targeting 37 targeting 39 and 37 targeting 43 ) 38 mirnas 39 and 39 and 40 p16 39 and 42 ink4a 41 ( 42 ink4a 42 ink4a 43 ) 44 and 49 promoter 45 p21 47 cip1/waf1 45 p21 49 promoter 46 ( 47 cip1/waf1 47 cip1/waf1 48 ) the role of [t] cells in innate immunity is not well defined . 0 ###LEFT-WALL### 2 role 0 ###LEFT-WALL### 9 is 0 ###LEFT-WALL### 13 . 1 the 2 role 2 role 3 of 2 role 9 is 3 of 5 cells 5 cells 6 in 6 in 8 immunity 7 innate 8 immunity 9 is 10 not 9 is 11 well 11 well 12 defined in this report , we show that a subset of human peripheral blood cd4 ( [+] [ )( cells [responds] to il - 12 plus il - 18 , but not to il - 12 [or] il - 18 alone , by producing ifn - [γ] in the absence of any antigenic stimulation or cell proliferation . 0 ###LEFT-WALL### 5 we 0 ###LEFT-WALL### 6 show 1 in 3 report 1 in 4 , 1 in 5 we 2 this 3 report 5 we 6 show 6 show 7 that 6 show 9 subset 8 a 9 subset 9 subset 10 of 10 of 14 cd4 11 human 13 blood 12 peripheral 13 blood 13 blood 14 cd4 14 cd4 23 - 15 ( 23 - 19 cells 21 to 19 cells 23 - 21 to 22 il 23 - 24 12 24 12 30 but 25 plus 26 il 25 plus 30 but 26 il 28 18 27 - 28 18 28 18 29 , 30 but 31 not 30 but 32 to 32 to 33 il 33 il 38 - 34 - 38 - 35 12 37 il 37 il 38 - 38 - 39 18 39 18 40 alone 39 18 50 of 40 alone 42 by 40 alone 47 in 41 , 42 by 42 by 43 producing 42 by 45 - 43 producing 44 ifn 47 in 49 absence 48 the 49 absence 50 of 54 or 51 any 53 stimulation 52 antigenic 53 stimulation 53 stimulation 54 or 54 or 56 proliferation 54 or 57 . 55 cell 56 proliferation intracellular staining reveals a small percentage of resting cd4 ( [+] [ )( cells ( 0.5 to 1.5 % ) capable of producing ifn - [γ] in response to il - 12 plus il - 18 . 0 ###LEFT-WALL### 1 intracellular 0 ###LEFT-WALL### 3 reveals 0 ###LEFT-WALL### 35 - 1 intracellular 2 staining 1 intracellular 3 reveals 3 reveals 6 percentage 4 a 5 small 4 a 6 percentage 5 small 6 percentage 6 percentage 7 of 6 percentage 21 capable 7 of 8 resting 8 resting 9 cd4 9 cd4 14 cells 10 ( 14 cells 14 cells 19 % 14 cells 20 ) 15 ( 19 % 16 0.5 17 to 17 to 18 1.5 17 to 19 % 19 % 20 ) 21 capable 22 of 22 of 23 producing 23 producing 24 ifn 23 producing 29 to 25 - 29 to 27 in 28 response 28 response 29 to 29 to 30 il 29 to 35 - 30 il 34 il 31 - 34 il 32 12 34 il 33 plus 34 il 34 il 35 - 35 - 36 18 35 - 37 . interestingly , both naïve ( cd45ra [(] + [ )( )( memory ( cd45ro [(] [+] ) ) cd4 [(] [+] ) populations were responsive to il - 12 plus il - 18 stimulation in producing ifn - [γ] . 0 ###LEFT-WALL### 23 populations 0 ###LEFT-WALL### 24 were 0 ###LEFT-WALL### 40 . 1 interestingly 23 populations 2 , 4 naïve 3 both 4 naïve 4 naïve 8 + 4 naïve 18 ) 4 naïve 23 populations 5 ( 8 + 6 cd45ra 8 + 8 + 12 memory 8 + 17 ) 12 memory 14 cd45ro 13 ( 14 cd45ro 14 cd45ro 17 ) 19 cd4 22 ) 19 cd4 23 populations 23 populations 24 were 24 were 25 responsive 25 responsive 26 to 26 to 27 il 27 il 29 12 28 - 29 12 29 12 30 plus 29 12 34 stimulation 29 12 38 - 30 plus 31 il 32 - 34 stimulation 33 18 34 stimulation 34 stimulation 35 in 34 stimulation 38 - 35 in 36 producing 36 producing 37 ifn the expression of ifn [-] γinduced by il - 12 and [il] - 18 is sensitive to rapamycin and sb203580 , indicating the possible involvement of mtor and p38 map kinase , respectively , in this synergistic pathway . 0 ###LEFT-WALL### 2 expression 0 ###LEFT-WALL### 15 is 0 ###LEFT-WALL### 39 . 1 the 2 expression 2 expression 3 of 2 expression 15 is 3 of 4 ifn 4 ifn 6 γinduced 4 ifn 7 by 7 by 8 il 8 il 11 and 9 - 10 12 10 12 11 and 11 and 14 18 13 - 14 18 15 is 19 and 16 sensitive 17 to 16 sensitive 19 and 17 to 18 rapamycin 19 and 20 sb203580 19 and 34 , 19 and 35 in 20 sb203580 22 indicating 21 , 22 indicating 22 indicating 28 and 22 indicating 33 respectively 22 indicating 34 , 23 the 25 involvement 24 possible 25 involvement 25 involvement 26 of 25 involvement 28 and 26 of 27 mtor 28 and 31 kinase 28 and 32 , 29 p38 31 kinase 30 map 31 kinase 32 , 33 respectively 33 respectively 34 , 35 in 38 pathway 36 this 38 pathway 37 synergistic 38 pathway while p38map [kinase] is involved in transcription , mtor is involved in message stabilization . 0 ###LEFT-WALL### 9 mtor 0 ###LEFT-WALL### 11 involved 0 ###LEFT-WALL### 15 . 1 while 2 p38map 1 while 5 involved 1 while 8 , 1 while 9 mtor 2 p38map 4 is 4 is 5 involved 5 involved 6 in 6 in 7 transcription 9 mtor 10 is 10 is 11 involved 11 involved 12 in 12 in 14 stabilization 13 message 14 stabilization we have also shown that nfκb family member , crel , but not gadd45β and gadd45γ , plays an important role in il - 12 plus [il] - 18 - induced ifn - γ transcription . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 36 . 1 we 17 , 2 have 4 shown 2 have 17 , 3 also 4 shown 4 shown 12 but 5 that 8 member 6 nfκb 7 family 7 family 8 member 8 member 9 , 9 , 10 crel 9 , 12 but 11 , 12 but 12 but 13 not 12 but 16 gadd45γ 14 gadd45β 15 and 15 and 16 gadd45γ 17 , 18 plays 17 , 22 in 18 plays 21 role 19 an 20 important 19 an 21 role 20 important 21 role 22 in 35 transcription 23 il 35 transcription 24 - 25 12 25 12 34 γ 26 plus 30 - 26 plus 33 - 26 plus 34 γ 28 - 30 - 29 18 30 - 30 - 32 ifn 30 - 33 - 31 induced 32 ifn 34 γ 35 transcription thus , the present study suggests that naïve cd4 [(] [+] [ )(t cells may participate in innate immunity or amplify adaptive immune responses through cytokine [-] induced antigen - independent cytokine production . 0 ###LEFT-WALL### 5 study 0 ###LEFT-WALL### 6 suggests 0 ###LEFT-WALL### 34 . 1 thus 2 , 1 thus 5 study 3 the 5 study 4 present 5 study 5 study 6 suggests 6 suggests 7 that 7 that 14 cells 7 that 20 or 8 naïve 14 cells 9 cd4 13 )(t 9 cd4 14 cells 15 may 16 participate 15 may 20 or 16 participate 17 in 17 in 19 immunity 18 innate 19 immunity 20 or 21 amplify 21 amplify 24 responses 21 amplify 25 through 22 adaptive 24 responses 23 immune 24 responses 25 through 33 production 26 cytokine 28 induced 28 induced 31 independent 29 antigen 30 - 29 antigen 31 independent 31 independent 33 production 32 cytokine 33 production testosterone levels in men older than 40 years can decrease at a rate of 1 % - 2 % per year , [and] reports show that more than 50 % of 80 - year [-] old men have testosterone levels consistent with hypogonadism . 0 ###LEFT-WALL### 1 testosterone 0 ###LEFT-WALL### 2 levels 1 testosterone 2 levels 2 levels 3 in 2 levels 4 men 4 men 5 older 4 men 8 years 4 men 10 decrease 4 men 11 at 5 older 6 than 6 than 7 40 8 years 9 can 9 can 10 decrease 11 at 13 rate 12 a 13 rate 13 rate 14 of 13 rate 24 reports 13 rate 25 show 14 of 16 % 15 1 16 % 16 % 19 % 17 - 19 % 18 2 19 % 19 % 20 per 19 % 22 , 20 per 21 year 24 reports 25 show 25 show 26 that 25 show 30 % 27 more 28 than 28 than 29 50 29 50 30 % 30 % 31 of 31 of 32 80 32 80 36 old 33 - 36 old 34 year 36 old 36 old 37 men 36 old 38 have 36 old 44 . 37 men 38 have 38 have 39 testosterone 39 testosterone 40 levels 40 levels 41 consistent 41 consistent 42 with 42 with 43 hypogonadism late - onset hypogonadism ( loh ) is a clinical and biochemical syndrome associated with advancing age and characterized by typical symptoms of serum testosterone deficiency . 0 ###LEFT-WALL### 4 hypogonadism 0 ###LEFT-WALL### 18 and 0 ###LEFT-WALL### 27 . 1 late 2 - 1 late 3 onset 3 onset 4 hypogonadism 4 hypogonadism 6 loh 4 hypogonadism 18 and 5 ( 6 loh 6 loh 7 ) 8 is 13 syndrome 8 is 18 and 9 a 13 syndrome 10 clinical 11 and 11 and 12 biochemical 11 and 13 syndrome 13 syndrome 14 associated 13 syndrome 15 with 15 with 16 advancing 16 advancing 17 age 18 and 19 characterized 18 and 20 by 18 and 26 deficiency 20 by 22 symptoms 21 typical 22 symptoms 22 symptoms 23 of 23 of 24 serum 25 testosterone 26 deficiency in recent decades , the concept of loh in ageing men has become familiar in european countries and the united states . 0 ###LEFT-WALL### 6 concept 0 ###LEFT-WALL### 13 become 0 ###LEFT-WALL### 22 . 1 in 3 decades 1 in 4 , 1 in 6 concept 2 recent 3 decades 5 the 6 concept 6 concept 7 of 6 concept 12 has 7 of 8 loh 8 loh 9 in 9 in 11 men 10 ageing 11 men 12 has 13 become 13 become 14 familiar 14 familiar 15 in 15 in 18 and 16 european 17 countries 17 countries 18 and 18 and 21 states 19 the 21 states 20 united 21 states it is also a topic of interest and debate throughout korea . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 12 . 1 it 2 is 2 is 3 also 2 is 5 topic 2 is 10 throughout 4 a 5 topic 5 topic 6 of 6 of 8 and 7 interest 8 and 8 and 9 debate 10 throughout 11 korea however , most of the data regarding advantages or disadvantages of testosterone replacement therapy ( trt ) as treatment for loh have been primarily obtained from studies on western populations ; therefore , studies of the effects of trt in asian men , who may have different serum testosterone compared to western men , are needed . 0 ###LEFT-WALL### 3 most 0 ###LEFT-WALL### 25 obtained 0 ###LEFT-WALL### 31 ; 0 ###LEFT-WALL### 57 . 1 however 2 , 1 however 3 most 3 most 4 of 3 most 7 regarding 3 most 22 have 4 of 6 data 5 the 6 data 7 regarding 9 or 8 advantages 9 or 9 or 10 disadvantages 9 or 18 as 10 disadvantages 11 of 11 of 14 therapy 12 testosterone 13 replacement 13 replacement 14 therapy 14 therapy 16 trt 15 ( 16 trt 16 trt 17 ) 18 as 19 treatment 19 treatment 20 for 20 for 21 loh 22 have 23 been 23 been 25 obtained 24 primarily 25 obtained 25 obtained 26 from 25 obtained 28 on 26 from 27 studies 28 on 30 populations 29 western 30 populations 31 ; 34 studies 31 ; 56 needed 32 therefore 33 , 32 therefore 34 studies 34 studies 35 of 34 studies 38 of 34 studies 55 are 35 of 37 effects 36 the 37 effects 38 of 39 trt 39 trt 40 in 40 in 42 men 41 asian 42 men 42 men 44 who 43 , 44 who 44 who 45 may 44 who 54 , 45 may 46 have 46 have 49 testosterone 47 different 48 serum 48 serum 49 testosterone 49 testosterone 50 compared 50 compared 51 to 51 to 53 men 52 western 53 men 55 are 56 needed trt is commonly prescribed in korea , despite the paucity of studies on the effects of trt in asian populations . 0 ###LEFT-WALL### 1 trt 0 ###LEFT-WALL### 4 prescribed 1 trt 2 is 2 is 4 prescribed 3 commonly 4 prescribed 4 prescribed 5 in 4 prescribed 8 despite 5 in 6 korea 7 , 8 despite 8 despite 10 paucity 8 despite 21 . 9 the 10 paucity 10 paucity 11 of 11 of 12 studies 12 studies 13 on 13 on 15 effects 14 the 15 effects 15 effects 16 of 16 of 17 trt 17 trt 18 in 18 in 20 populations 19 asian 20 populations data from various trt studies based on korean have shown its efficacy in increasing serum testosterone levels and improving subjective symptoms as assessed by questionnaires . 0 ###LEFT-WALL### 1 data 0 ###LEFT-WALL### 10 shown 0 ###LEFT-WALL### 26 . 1 data 2 from 1 data 5 studies 1 data 6 based 1 data 9 have 2 from 4 trt 3 various 4 trt 5 studies 6 based 6 based 7 on 7 on 8 korean 9 have 10 shown 10 shown 18 and 10 shown 24 by 11 its 12 efficacy 12 efficacy 13 in 12 efficacy 18 and 13 in 14 increasing 14 increasing 17 levels 15 serum 17 levels 16 testosterone 17 levels 18 and 21 symptoms 18 and 23 assessed 19 improving 21 symptoms 20 subjective 21 symptoms 22 as 23 assessed 24 by 25 questionnaires currently , patches and short - acting intramuscular injections are displaced by gels and long - acting formulations . 0 ###LEFT-WALL### 9 injections 0 ###LEFT-WALL### 11 displaced 0 ###LEFT-WALL### 19 . 1 currently 2 , 1 currently 9 injections 3 patches 4 and 4 and 5 short 4 and 6 - 4 and 7 acting 4 and 9 injections 7 acting 8 intramuscular 9 injections 10 are 10 are 11 displaced 11 displaced 12 by 12 by 14 and 13 gels 14 and 14 and 18 formulations 15 long 16 - 15 long 18 formulations 17 acting 18 formulations however [,] to prevent overdiagnosis and overtreatment , indication for trt should include both low testosterone levels and symptoms and signs of hypogonadism . 0 ###LEFT-WALL### 3 to 0 ###LEFT-WALL### 4 prevent 0 ###LEFT-WALL### 24 . 1 however 3 to 3 to 4 prevent 4 prevent 6 and 4 prevent 10 for 5 overdiagnosis 6 and 6 and 9 indication 7 overtreatment 8 , 7 overtreatment 9 indication 10 for 11 trt 11 trt 20 and 11 trt 22 of 12 should 13 include 12 should 20 and 13 include 18 and 14 both 17 levels 15 low 17 levels 16 testosterone 17 levels 17 levels 18 and 18 and 19 symptoms 20 and 21 signs 22 of 23 hypogonadism background : the superficial musculoaponeurotic system ( smas ) has inherent viscoelastic properties , although the optimal tension levels to minimize tissue relaxation have not been defined . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 27 defined 0 ###LEFT-WALL### 28 . 2 : 6 system 2 : 10 has 3 the 6 system 4 superficial 6 system 5 musculoaponeurotic 6 system 6 system 8 smas 6 system 10 has 7 ( 8 smas 8 smas 9 ) 10 has 13 properties 10 has 15 although 11 inherent 13 properties 12 viscoelastic 13 properties 14 , 15 although 15 although 19 levels 16 the 19 levels 17 optimal 18 tension 18 tension 19 levels 19 levels 20 to 19 levels 21 minimize 19 levels 24 have 20 to 21 minimize 21 minimize 23 relaxation 22 tissue 23 relaxation 24 have 25 not 24 have 26 been 26 been 27 defined this study evaluated the viscoelastic properties of the smas within the biomechanical parameters of the high - smas rhytidectomy . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 evaluated 0 ###LEFT-WALL### 20 . 1 this 2 study 2 study 3 evaluated 3 evaluated 6 properties 3 evaluated 19 rhytidectomy 4 the 6 properties 5 viscoelastic 6 properties 6 properties 7 of 6 properties 19 rhytidectomy 7 of 9 smas 8 the 9 smas 9 smas 10 within 9 smas 14 of 10 within 13 parameters 11 the 13 parameters 12 biomechanical 13 parameters 14 of 18 smas 15 the 18 smas 16 high 17 - 16 high 18 smas fresh samples of lateral , preparotid smas were then harvested and evaluated ex vivo for bursting strength , stress relaxation , and creep . 0 ###LEFT-WALL### 22 and 0 ###LEFT-WALL### 24 . 1 fresh 2 samples 2 samples 3 of 2 samples 22 and 3 of 6 preparotid 4 lateral 5 , 4 lateral 6 preparotid 6 preparotid 7 smas 6 preparotid 12 evaluated 7 smas 11 and 8 were 10 harvested 8 were 11 and 9 then 10 harvested 11 and 12 evaluated 12 evaluated 14 vivo 12 evaluated 15 for 13 ex 14 vivo 15 for 16 bursting 16 bursting 17 strength 17 strength 20 relaxation 18 , 20 relaxation 19 stress 20 relaxation 20 relaxation 21 , 22 and 23 creep results : the force applied to the superior , preauricular smas intraoperatively ( 7.21 ± [0.87] n ) was significantly lower than that of the inferior mastoid point of fixation ( 9.59 ± [1.8] n ) ( p < 0.001 ) . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 4 force 2 : 19 was 2 : 42 . 3 the 4 force 4 force 5 applied 4 force 17 n 4 force 19 was 5 applied 6 to 5 applied 12 intraoperatively 6 to 11 smas 7 the 11 smas 8 superior 9 , 8 superior 11 smas 10 preauricular 11 smas 13 ( 17 n 14 7.21 17 n 15 ± 17 n 17 n 18 ) 19 was 20 significantly 19 was 21 lower 21 lower 22 than 22 than 23 that 23 that 24 of 24 of 28 point 25 the 28 point 26 inferior 28 point 27 mastoid 28 point 28 point 29 of 28 point 39 < 29 of 30 fixation 30 fixation 35 n 31 ( 35 n 32 9.59 35 n 33 ± 35 n 35 n 36 ) 37 ( 39 < 38 p 39 < 39 < 40 0.001 39 < 41 ) the bursting force of the smas was 55.7 n , with the average bursting pressure of 224.97 psi . 0 ###LEFT-WALL### 3 force 0 ###LEFT-WALL### 7 was 1 the 3 force 2 bursting 3 force 3 force 4 of 3 force 7 was 4 of 6 smas 5 the 6 smas 7 was 9 n 7 was 11 with 8 55.7 9 n 10 , 11 with 11 with 13 average 11 with 14 bursting 11 with 19 . 12 the 13 average 14 bursting 15 pressure 15 pressure 16 of 16 of 18 psi 17 224.97 18 psi [the] in vivo force applied to the smas was found to be only 15 percent of its total bursting strength . 0 ###LEFT-WALL### 4 force 0 ###LEFT-WALL### 12 be 0 ###LEFT-WALL### 21 . 2 in 3 vivo 3 vivo 4 force 4 force 5 applied 4 force 9 was 5 applied 6 to 6 to 8 smas 7 the 8 smas 9 was 10 found 10 found 11 to 11 to 12 be 12 be 15 percent 13 only 14 15 14 15 15 percent 15 percent 16 of 15 percent 19 bursting 16 of 18 total 17 its 18 total 19 bursting 20 strength the deformational load of the high - smas face lift caused only a 14 percent creep in the tissue ex vivo . 0 ###LEFT-WALL### 3 load 0 ###LEFT-WALL### 11 caused 0 ###LEFT-WALL### 22 . 1 the 3 load 2 deformational 3 load 3 load 4 of 3 load 11 caused 4 of 10 lift 5 the 10 lift 6 high 7 - 6 high 10 lift 8 smas 10 lift 9 face 10 lift 11 caused 12 only 11 caused 16 creep 11 caused 17 in 11 caused 21 vivo 13 a 16 creep 14 14 15 percent 15 percent 16 creep 17 in 19 tissue 18 the 19 tissue 20 ex 21 vivo conclusions : [the] in vivo tension in a high - smas face lift is predictable , with the force applied to the mastoid point being significantly greater than that of the superior preauricular point . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 5 vivo 2 : 14 is 4 in 5 vivo 5 vivo 14 is 6 tension 7 in 6 tension 14 is 7 in 13 lift 8 a 9 high 8 a 13 lift 9 high 10 - 9 high 13 lift 11 smas 12 face 12 face 13 lift 14 is 15 predictable 15 predictable 17 with 16 , 17 with 17 with 19 force 17 with 35 . 18 the 19 force 19 force 20 applied 19 force 25 being 20 applied 21 to 21 to 24 point 22 the 24 point 23 mastoid 24 point 25 being 26 significantly 25 being 27 greater 27 greater 28 than 28 than 29 that 28 than 30 of 30 of 34 point 31 the 34 point 32 superior 34 point 33 preauricular 34 point this intraoperative force is only a fraction of the tissue 's inherent bursting strength , contributing to the minimal stress relaxation and creep observed in this study . 0 ###LEFT-WALL### 3 force 0 ###LEFT-WALL### 4 is 0 ###LEFT-WALL### 24 observed 0 ###LEFT-WALL### 28 . 1 this 2 intraoperative 2 intraoperative 3 force 3 force 4 is 4 is 5 only 4 is 7 fraction 6 a 7 fraction 7 fraction 8 of 8 of 14 strength 9 the 10 tissue 10 tissue 11 's 11 's 14 strength 12 inherent 14 strength 13 bursting 14 strength 15 , 24 observed 16 contributing 17 to 16 contributing 24 observed 17 to 22 and 18 the 21 relaxation 19 minimal 20 stress 20 stress 21 relaxation 21 relaxation 22 and 22 and 23 creep 24 observed 25 in 25 in 27 study 26 this 27 study these biomechanical properties likely contribute to the effective and long - lasting correction of facial aging with the high - smas technique . 0 ###LEFT-WALL### 3 properties 0 ###LEFT-WALL### 5 contribute 0 ###LEFT-WALL### 23 . 1 these 3 properties 2 biomechanical 3 properties 3 properties 5 contribute 4 likely 5 contribute 5 contribute 6 to 5 contribute 17 with 6 to 9 and 7 the 8 effective 8 effective 9 and 9 and 13 correction 10 long 11 - 10 long 13 correction 12 lasting 13 correction 13 correction 14 of 14 of 16 aging 15 facial 16 aging 17 with 22 technique 18 the 22 technique 19 high 20 - 19 high 22 technique 21 smas 22 technique clinical question/level of evidence : therapeutic , iv . 0 ###LEFT-WALL### 4 evidence 0 ###LEFT-WALL### 5 : 1 clinical 2 question/level 2 question/level 3 of 3 of 4 evidence 5 : 8 iv 5 : 9 . 6 therapeutic 7 , 6 therapeutic 8 iv practitioners training the older adult may benefit from a low - cost , [easy] - to [-] administer field test [of] upper body power . 0 ###LEFT-WALL### 1 practitioners 0 ###LEFT-WALL### 7 benefit 0 ###LEFT-WALL### 13 , 0 ###LEFT-WALL### 25 . 1 practitioners 2 training 1 practitioners 6 may 2 training 5 adult 3 the 5 adult 4 older 5 adult 6 may 7 benefit 7 benefit 8 from 8 from 10 low 9 a 10 low 10 low 12 cost 11 - 12 cost 12 cost 13 , 13 , 15 - 13 , 18 administer 15 - 16 to 16 to 18 administer 18 administer 24 power 19 field 20 test 20 test 23 body 22 upper 23 body 23 body 24 power this study evaluated validity and reliability of the seated medicine ball [throw] ( smbt ) in older adults . 0 ###LEFT-WALL### 5 and 0 ###LEFT-WALL### 19 . 1 this 4 validity 2 study 3 evaluated 3 evaluated 4 validity 4 validity 5 and 5 and 6 reliability 5 and 7 of 5 and 16 in 7 of 11 ball 8 the 11 ball 9 seated 10 medicine 10 medicine 11 ball 11 ball 14 smbt 13 ( 14 smbt 14 smbt 15 ) 16 in 18 adults 17 older 18 adults subjects [(] n = 33 ; age 72.4 ± 5.2 years [ )(completed 6 trials of an smbt in each of 2 testing days and 2 ball masses ( 1.5 and 3.0 kg ) . 0 ###LEFT-WALL### 1 subjects 0 ###LEFT-WALL### 4 = 0 ###LEFT-WALL### 6 ; 0 ###LEFT-WALL### 13 )(completed 0 ###LEFT-WALL### 35 . 1 subjects 4 = 3 n 4 = 4 = 5 33 6 ; 7 age 7 age 8 72.4 7 age 9 ± 9 ± 10 5.2 9 ± 11 years 9 ± 13 )(completed 11 years 13 )(completed 13 )(completed 15 trials 14 6 15 trials 15 trials 16 of 15 trials 23 testing 16 of 18 smbt 17 an 18 smbt 18 smbt 19 in 18 smbt 21 of 19 in 20 each 21 of 22 2 23 testing 25 and 24 days 25 and 25 and 28 masses 25 and 33 kg 26 2 28 masses 27 ball 28 masses 29 ( 33 kg 30 1.5 31 and 31 and 32 3.0 31 and 33 kg 33 kg 34 ) subjects also completed 6 trials of an explosive push - up [(] epu ) on a force plate over 2 testing days . 0 ###LEFT-WALL### 1 subjects 0 ###LEFT-WALL### 3 completed 0 ###LEFT-WALL### 23 . 1 subjects 3 completed 2 also 3 completed 3 completed 5 trials 3 completed 11 up 3 completed 15 on 3 completed 19 over 4 6 5 trials 5 trials 6 of 6 of 9 push 7 an 8 explosive 7 an 9 push 8 explosive 9 push 10 - 11 up 11 up 13 epu 11 up 14 ) 15 on 18 plate 16 a 18 plate 17 force 18 plate 19 over 20 2 20 2 21 testing 21 testing 22 days validity was assessed via a pearson product [-] moment correlation ( [ppm] [ )(between smbt and epu maximal vertical force . 0 ###LEFT-WALL### 1 validity 0 ###LEFT-WALL### 3 assessed 1 validity 2 was 2 was 3 assessed 3 assessed 4 via 4 via 10 correlation 5 a 10 correlation 6 pearson 7 product 7 product 10 correlation 9 moment 10 correlation 10 correlation 14 )(between 11 ( 14 )(between 14 )(between 16 and 14 )(between 21 . 15 smbt 16 and 16 and 20 force 17 epu 20 force 18 maximal 19 vertical 19 vertical 20 force reliability of the smbt was determined using ppms [(] [r] [ )(, intraclass [correlation] ( icc , r ) and bland - altman plots ( baps ) . 0 ###LEFT-WALL### 1 reliability 0 ###LEFT-WALL### 6 determined 0 ###LEFT-WALL### 28 . 1 reliability 2 of 1 reliability 5 was 2 of 4 smbt 3 the 4 smbt 5 was 6 determined 6 determined 7 using 7 using 20 and 8 ppms 12 )(, 12 )(, 13 intraclass 12 )(, 20 and 13 intraclass 16 icc 15 ( 16 icc 16 icc 18 r 16 icc 19 ) 17 , 18 r 18 r 19 ) 20 and 21 bland 20 and 24 plots 22 - 24 plots 23 altman 24 plots 24 plots 26 baps 24 plots 27 ) 25 ( 26 baps 26 baps 27 ) for validity , the association between the smbt and the epu revealed a ppm of [r] = 0.641 and [r] = 0.614 for the 1.5 - [and] 3.0 - [kg] medicine balls , respectively . 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 12 revealed 0 ###LEFT-WALL### 35 . 1 for 2 validity 1 for 3 , 1 for 9 and 4 the 5 association 5 association 6 between 5 association 9 and 6 between 8 smbt 7 the 8 smbt 9 and 11 epu 9 and 12 revealed 10 the 11 epu 12 revealed 14 ppm 12 revealed 34 respectively 13 a 14 ppm 14 ppm 15 of 15 of 19 and 17 = 19 and 18 0.641 19 and 19 and 22 0.614 19 and 23 for 19 and 28 3.0 19 and 32 balls 21 = 22 0.614 23 for 25 1.5 24 the 25 1.5 26 - 28 3.0 28 3.0 29 - 29 - 32 balls 31 medicine 32 balls 32 balls 33 , test - retest reliability of the 1.5 - and 3.0 - [kg] smbt was r = 0.967 [and] r = 0.958 , respectively . 0 ###LEFT-WALL### 1 test 0 ###LEFT-WALL### 2 - 2 - 3 retest 2 - 9 and 2 - 14 was 2 - 24 . 3 retest 4 reliability 4 reliability 5 of 5 of 7 1.5 6 the 7 1.5 8 - 9 and 9 and 10 3.0 9 and 11 - 10 3.0 11 - 11 - 13 smbt 13 smbt 14 was 14 was 16 = 14 was 20 = 14 was 23 respectively 15 r 16 = 16 = 17 0.967 19 r 20 = 20 = 21 0.958 20 = 22 , the icc values of the 1.5 - and 3.0 [-] kg smbt were r = 0.994 and 0.989 , respectively . 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 13 were 1 the 3 values 2 icc 3 values 3 values 4 of 3 values 8 and 4 of 6 1.5 5 the 6 1.5 7 - 8 and 8 and 12 smbt 8 and 13 were 9 3.0 11 kg 11 kg 12 smbt 13 were 15 = 13 were 20 respectively 14 r 15 = 15 = 17 and 16 0.994 17 and 17 and 18 0.989 19 , 20 respectively 20 respectively 21 . the baps revealed 94 % of the differences between day 1 and 2 scores were within the 95 % confidence interval of the mean difference . 0 ###LEFT-WALL### 2 baps 0 ###LEFT-WALL### 3 revealed 0 ###LEFT-WALL### 26 . 1 the 2 baps 2 baps 3 revealed 3 revealed 5 % 3 revealed 15 were 4 94 5 % 5 % 6 of 5 % 15 were 6 of 8 differences 7 the 8 differences 8 differences 9 between 9 between 14 scores 10 day 12 and 10 day 14 scores 11 1 12 and 12 and 13 2 15 were 16 within 16 within 21 interval 17 the 21 interval 18 95 19 % 19 % 21 interval 20 confidence 21 interval 21 interval 22 of 22 of 25 difference 23 the 25 difference 24 mean 25 difference test - retest reliability for the epu was r = 0.944 , r = 0.969 . 0 ###LEFT-WALL### 1 test 0 ###LEFT-WALL### 2 - 0 ###LEFT-WALL### 8 was 0 ###LEFT-WALL### 16 . 2 - 3 retest 3 retest 4 reliability 3 retest 5 for 5 for 7 epu 6 the 7 epu 7 epu 8 was 8 was 10 = 8 was 14 = 9 r 10 = 10 = 11 0.944 10 = 12 , 12 , 14 = 13 r 14 = 14 = 15 0.969 the baps showed 94 % of the differences between day 1 and 2 scores were within the 95 % confidence interval of the mean difference [,] for both medicine ball throws . 0 ###LEFT-WALL### 2 baps 0 ###LEFT-WALL### 3 showed 0 ###LEFT-WALL### 32 . 1 the 2 baps 2 baps 3 showed 3 showed 5 % 3 showed 9 between 3 showed 14 scores 3 showed 15 were 4 94 5 % 5 % 6 of 6 of 8 differences 7 the 8 differences 9 between 10 day 11 1 12 and 12 and 13 2 12 and 14 scores 14 scores 15 were 15 were 16 within 16 within 21 interval 17 the 21 interval 18 95 21 interval 19 % 20 confidence 20 confidence 21 interval 21 interval 22 of 22 of 25 difference 23 the 25 difference 24 mean 25 difference 25 difference 27 for 25 difference 30 ball 25 difference 31 throws 27 for 28 both 29 medicine 30 ball 30 ball 31 throws in conclusion , for the older adult , the smbt appears to be highly reliable test [of] upper body power . 0 ###LEFT-WALL### 2 conclusion 0 ###LEFT-WALL### 3 , 0 ###LEFT-WALL### 21 . 1 in 2 conclusion 3 , 10 smbt 3 , 11 appears 4 for 7 adult 4 for 8 , 4 for 10 smbt 5 the 7 adult 6 older 7 adult 9 the 10 smbt 10 smbt 11 appears 11 appears 12 to 11 appears 13 be 12 to 13 be 13 be 20 power 14 highly 15 reliable 15 reliable 16 test 16 test 20 power 18 upper 19 body 19 body 20 power its validity relative to the maximal force exerted during the epu is modest . 0 ###LEFT-WALL### 2 validity 0 ###LEFT-WALL### 12 is 0 ###LEFT-WALL### 14 . 1 its 2 validity 2 validity 3 relative 2 validity 12 is 3 relative 4 to 4 to 7 force 5 the 7 force 6 maximal 7 force 7 force 8 exerted 8 exerted 9 during 9 during 11 epu 10 the 11 epu 12 is 13 modest the smbt is an inexpensive , safe , and repeatable measure of upper body power for the older adult . 0 ###LEFT-WALL### 2 smbt 0 ###LEFT-WALL### 3 is 0 ###LEFT-WALL### 20 . 1 the 2 smbt 2 smbt 3 is 3 is 15 power 4 an 11 measure 5 inexpensive 6 , 6 , 7 safe 6 , 9 and 8 , 9 and 9 and 10 repeatable 9 and 11 measure 11 measure 12 of 11 measure 15 power 12 of 15 power 13 upper 14 body 14 body 15 power 15 power 16 for 16 for 19 adult 17 the 19 adult 18 older 19 adult objectives : this study examines the effect of age on rate [of] cognitive decline [in] different stages of dementia , of nursing home [and] assisted - living residents . 0 ###LEFT-WALL### 1 objectives 0 ###LEFT-WALL### 2 : 2 : 4 study 2 : 5 examines 2 : 29 . 3 this 4 study 4 study 5 examines 5 examines 7 effect 5 examines 10 on 6 the 7 effect 7 effect 8 of 8 of 9 age 10 on 17 stages 11 rate 17 stages 13 cognitive 14 decline 14 decline 17 stages 16 different 17 stages 17 stages 18 of 17 stages 27 living 18 of 19 dementia 19 dementia 21 of 20 , 21 of 21 of 22 nursing 21 of 26 - 22 nursing 23 home 23 home 25 assisted 27 living 28 residents methods : in this longitudinal study , the mini mental state examination ( mmse ) was used to measure rate of cognitive decline in subjects who were nondemented [[] clinical dementia rating ( cdr )=0 [;] n=353 []] , questionably demented [(] cdr=0.5 [;] n=121 [ )(, or frankly demented [(] cdr≥1 [;] n=213 ) at baseline . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 2 : 14 mmse 3 in 6 study 3 in 7 , 3 in 14 mmse 4 this 5 longitudinal 5 longitudinal 6 study 8 the 14 mmse 9 mini 10 mental 10 mental 11 state 11 state 12 examination 12 examination 14 mmse 13 ( 14 mmse 14 mmse 15 ) 14 mmse 16 was 16 was 17 used 17 used 18 to 17 used 19 measure 18 to 19 measure 19 measure 20 rate 19 measure 24 in 20 rate 21 of 21 of 23 decline 22 cognitive 23 decline 24 in 25 subjects 25 subjects 26 who 25 subjects 27 were 26 who 27 were 27 were 37 n=353 28 nondemented 35 )=0 30 clinical 31 dementia 31 dementia 32 rating 32 rating 34 cdr 33 ( 34 cdr 34 cdr 35 )=0 35 )=0 37 n=353 37 n=353 48 or 39 , 48 or 40 questionably 41 demented 41 demented 45 n=121 43 cdr=0.5 45 n=121 45 n=121 48 or 47 )(, 48 or 48 or 54 n=213 48 or 55 ) 48 or 56 at 48 or 58 . 49 frankly 50 demented 50 demented 54 n=213 52 cdr≥1 54 n=213 56 at 57 baseline results : a generalized estimating equation was used to model the mmse scores over time ( mean [follow] - up 2.9±2.0 [y] ) . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 6 equation 2 : 8 used 2 : 24 . 3 a 6 equation 4 generalized 6 equation 5 estimating 6 equation 6 equation 7 was 7 was 8 used 8 used 9 to 8 used 14 over 9 to 10 model 10 model 13 scores 11 the 13 scores 12 mmse 13 scores 14 over 15 time 15 time 21 2.9±2.0 16 ( 21 2.9±2.0 17 mean 19 - 17 mean 21 2.9±2.0 20 up 21 2.9±2.0 21 2.9±2.0 23 ) the generalized estimating equation model had the mmse scores at successive [follow] - up time points as dependent variables and had linear and quadratic age , follow - up time from baseline , cdr at baseline , and all the interactions among them as independent variables , controlling for mmse at baseline , sex , race , and education . 0 ###LEFT-WALL### 5 model 0 ###LEFT-WALL### 6 had 0 ###LEFT-WALL### 60 . 1 the 5 model 2 generalized 4 equation 3 estimating 4 equation 4 equation 5 model 5 model 6 had 6 had 9 scores 6 had 10 at 6 had 44 as 7 the 9 scores 8 mmse 9 scores 10 at 15 time 11 successive 13 - 11 successive 15 time 14 up 15 time 15 time 20 and 15 time 23 and 15 time 26 , 16 points 17 as 16 points 20 and 17 as 19 variables 18 dependent 19 variables 20 and 21 had 22 linear 23 and 23 and 24 quadratic 23 and 26 , 25 age 26 , 26 , 27 follow 26 , 35 at 26 , 41 interactions 27 follow 29 up 27 follow 34 cdr 28 - 29 up 29 up 30 time 29 up 33 , 30 time 31 from 31 from 32 baseline 35 at 38 and 36 baseline 38 and 37 , 38 and 38 and 39 all 40 the 41 interactions 41 interactions 42 among 42 among 43 them 44 as 58 and 45 independent 46 variables 46 variables 47 , 47 , 48 controlling 47 , 58 and 48 controlling 49 for 49 for 50 mmse 50 mmse 51 at 51 at 52 baseline 52 baseline 54 sex 53 , 54 sex 54 sex 56 race 54 sex 57 , 55 , 56 race 56 race 57 , 58 and 59 education the mean age of the entire sample was 85.2±7.4 years at baseline . 0 ###LEFT-WALL### 3 age 0 ###LEFT-WALL### 9 85.2±7.4 0 ###LEFT-WALL### 13 . 1 the 3 age 2 mean 3 age 3 age 4 of 3 age 8 was 4 of 7 sample 5 the 7 sample 6 entire 7 sample 8 was 9 85.2±7.4 9 85.2±7.4 10 years 9 85.2±7.4 11 at 11 at 12 baseline there were no significant interactions of linear age effects [with] rate [of] cognitive [decline] . 0 ###LEFT-WALL### 1 there 0 ###LEFT-WALL### 2 were 0 ###LEFT-WALL### 15 . 1 there 2 were 2 were 5 interactions 2 were 13 cognitive 3 no 5 interactions 4 significant 5 interactions 5 interactions 6 of 6 of 8 age 7 linear 8 age 8 age 9 effects 8 age 11 rate 9 effects 11 rate the analysis of interaction of quadratic age with rate of cognitive decline showed complex relationships : in the nondemented group , there was no substantial quadratic association of age with the rate of cognitive decline ( p=0.13 ) [;] in the questionable demented group [,] the oldest subjects declined relatively faster [(] p=0.02 [ )( and [in] the demented group , the youngest and oldest subjects tended to decline relatively less than subjects in the intermediate ages ( p=0.07 [ )( 1 the 2 analysis 2 analysis 3 of 2 analysis 13 showed 3 of 4 interaction 4 interaction 5 of 4 interaction 10 of 5 of 7 age 6 quadratic 7 age 7 age 8 with 8 with 9 rate 10 of 12 decline 11 cognitive 12 decline 13 showed 15 relationships 13 showed 16 : 14 complex 15 relationships 16 : 22 there 16 : 23 was 17 in 20 group 17 in 21 , 17 in 22 there 18 the 20 group 19 nondemented 20 group 22 there 23 was 23 was 27 association 24 no 27 association 25 substantial 27 association 26 quadratic 27 association 27 association 28 of 28 of 29 age 29 age 30 with 29 age 40 in 30 with 32 rate 31 the 32 rate 32 rate 33 of 33 of 35 decline 34 cognitive 35 decline 35 decline 37 p=0.13 36 ( 37 p=0.13 37 p=0.13 38 ) 40 in 44 group 41 the 44 group 42 questionable 44 group 43 demented 44 group 44 group 48 subjects 44 group 49 declined 46 the 47 oldest 46 the 48 subjects 48 subjects 49 declined 49 declined 56 and 50 relatively 51 faster 51 faster 53 p=0.02 53 p=0.02 56 and 56 and 60 group 56 and 61 , 56 and 66 subjects 56 and 67 tended 58 the 60 group 59 demented 60 group 62 the 64 and 62 the 66 subjects 63 youngest 64 and 64 and 65 oldest 66 subjects 67 tended 67 tended 68 to 67 tended 72 than 68 to 69 decline 69 decline 71 less 70 relatively 71 less 72 than 73 subjects 73 subjects 74 in 74 in 77 ages 75 the 77 ages 76 intermediate 77 ages 77 ages 79 p=0.07 78 ( 79 p=0.07 79 p=0.07 81 )( conclusions : this study adds an additional aspect to the complexity of the association between age and rate [of] cognitive decline , showing that the direction and amplitude of this effect differs according to the stage along the course [of] cognitive decline . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 4 study 2 : 5 adds 2 : 27 and 2 : 43 . 3 this 4 study 4 study 5 adds 5 adds 8 aspect 5 adds 15 between 6 an 8 aspect 7 additional 8 aspect 8 aspect 9 to 8 aspect 12 of 9 to 11 complexity 10 the 11 complexity 12 of 14 association 13 the 14 association 15 between 17 and 16 age 17 and 17 and 21 decline 17 and 22 , 17 and 23 showing 18 rate 21 decline 20 cognitive 21 decline 23 showing 24 that 23 showing 26 direction 25 the 26 direction 27 and 28 amplitude 27 and 32 differs 28 amplitude 29 of 28 amplitude 32 differs 29 of 31 effect 30 this 31 effect 32 differs 34 to 32 differs 37 along 33 according 34 to 34 to 36 stage 35 the 36 stage 37 along 42 decline 38 the 42 decline 39 course 42 decline 41 cognitive 42 decline background : unintentional loss of weight and muscle due to aging and disease has been associated with increased mortality . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 20 . 2 : 7 and 2 : 12 and 3 unintentional 4 loss 4 loss 5 of 4 loss 7 and 5 of 6 weight 7 and 8 muscle 7 and 9 due 9 due 10 to 10 to 11 aging 12 and 13 disease 12 and 16 associated 13 disease 14 has 14 has 15 been 15 been 16 associated 16 associated 17 with 17 with 19 mortality 18 increased 19 mortality wasting and weight loss [occur] in hiv infection even in the modern era of effective antiretroviral therapy . 0 ###LEFT-WALL### 2 and 0 ###LEFT-WALL### 18 . 1 wasting 2 and 2 and 4 loss 2 and 6 in 3 weight 4 loss 6 in 8 infection 7 hiv 8 infection 8 infection 9 even 9 even 10 in 10 in 13 era 11 the 13 era 12 modern 13 era 13 era 14 of 14 of 17 therapy 15 effective 17 therapy 16 antiretroviral 17 therapy methods : we determined the association of mri - measured regional and total skeletal muscle and adipose tissue with 5 [-] year , all - cause mortality in 922 hiv - infected persons in the study of fat redistribution and metabolic change in hiv infection ( fram ) . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 32 infected 0 ###LEFT-WALL### 49 . 2 : 3 we 2 : 4 determined 2 : 9 - 3 we 4 determined 4 determined 6 association 5 the 6 association 6 association 7 of 7 of 8 mri 9 - 16 and 10 measured 15 muscle 11 regional 12 and 12 and 13 total 12 and 15 muscle 14 skeletal 15 muscle 15 muscle 16 and 16 and 17 adipose 16 and 18 tissue 16 and 32 infected 18 tissue 19 with 18 tissue 25 - 18 tissue 32 infected 19 with 22 year 20 5 22 year 23 , 25 - 24 all 25 - 25 - 27 mortality 25 - 31 - 26 cause 27 mortality 27 mortality 28 in 28 in 30 hiv 29 922 30 hiv 32 infected 33 persons 32 infected 43 in 33 persons 34 in 33 persons 37 of 34 in 36 study 35 the 36 study 37 of 40 and 38 fat 39 redistribution 39 redistribution 40 and 40 and 42 change 41 metabolic 42 change 43 in 45 infection 44 hiv 45 infection 45 infection 47 fram 46 ( 47 fram 47 fram 48 ) results : after 5 years [of] follow - up , hiv - infected participants with arm skeletal muscle in the lowest tertile had a mortality rate of 23 % , compared with 11 and 8 % for those in the middle and [highest] tertiles . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 11 hiv 2 : 31 compared 2 : 45 . 3 after 5 years 3 after 7 follow 3 after 11 hiv 4 5 5 years 5 years 7 follow 8 - 9 up 9 up 10 , 9 up 11 hiv 11 hiv 14 participants 11 hiv 31 compared 12 - 14 participants 13 infected 14 participants 14 participants 15 with 14 participants 22 tertile 14 participants 26 rate 14 participants 27 of 14 participants 30 , 15 with 18 muscle 16 arm 18 muscle 17 skeletal 18 muscle 18 muscle 19 in 19 in 21 lowest 20 the 21 lowest 22 tertile 23 had 23 had 25 mortality 23 had 26 rate 24 a 25 mortality 27 of 29 % 28 23 29 % 31 compared 32 with 32 with 36 % 32 with 39 in 33 11 34 and 34 and 35 8 34 and 36 % 36 % 37 for 37 for 38 those 39 in 42 and 40 the 41 middle 41 middle 42 and 42 and 44 tertiles after multivariable adjustment for demographics , cardiovascular risk factors , hiv - related factors , inflammatory markers , and renal disease , we found that lower arm skeletal muscle , lower leg skeletal muscle and higher visceral adipose tissue ( vat ) were each independently associated with increased mortality . 0 ###LEFT-WALL### 19 and 0 ###LEFT-WALL### 50 . 1 after 3 adjustment 1 after 13 related 1 after 19 and 2 multivariable 3 adjustment 3 adjustment 4 for 3 adjustment 11 hiv 3 adjustment 13 related 4 for 5 demographics 5 demographics 9 factors 6 , 9 factors 7 cardiovascular 9 factors 8 risk 9 factors 9 factors 10 , 10 , 11 hiv 11 hiv 12 - 14 factors 15 , 15 , 17 markers 15 , 19 and 16 inflammatory 17 markers 18 , 19 and 19 and 21 disease 19 and 22 , 19 and 23 we 19 and 24 found 19 and 35 and 19 and 43 were 20 renal 21 disease 23 we 24 found 24 found 29 muscle 25 that 29 muscle 26 lower 27 arm 27 arm 29 muscle 28 skeletal 29 muscle 30 , 35 and 31 lower 32 leg 32 leg 34 muscle 33 skeletal 34 muscle 34 muscle 35 and 35 and 39 tissue 35 and 41 vat 35 and 42 ) 36 higher 39 tissue 37 visceral 38 adipose 38 adipose 39 tissue 40 ( 41 vat 41 vat 42 ) 43 were 46 associated 44 each 46 associated 45 independently 46 associated 46 associated 47 with 47 with 49 mortality 48 increased 49 mortality those in the lowest tertile [of] arm or leg skeletal muscle had higher odds of death [ arm [:] odds ratio [(] or ) = 2.0 , 95 % confidence [interval] ( ci ) 0.96 - 4.0 ; leg : or = 2.4 , 95 % ci 1.2 - 4.8 ] compared with the highest respective tertiles . 0 ###LEFT-WALL### 16 death 0 ###LEFT-WALL### 25 = 0 ###LEFT-WALL### 38 ; 0 ###LEFT-WALL### 58 . 1 those 2 in 1 those 8 or 2 in 7 arm 3 the 4 lowest 3 the 7 arm 5 tertile 7 arm 8 or 9 leg 8 or 11 muscle 8 or 15 of 8 or 16 death 10 skeletal 11 muscle 11 muscle 12 had 12 had 14 odds 13 higher 14 odds 14 odds 15 of 16 death 23 or 16 death 25 = 17 [ 23 or 18 arm 20 odds 20 odds 23 or 21 ratio 23 or 23 or 24 ) 25 = 26 2.0 25 = 36 - 26 2.0 30 confidence 27 , 30 confidence 28 95 29 % 29 % 30 confidence 30 confidence 33 ci 30 confidence 34 ) 32 ( 33 ci 33 ci 34 ) 35 0.96 36 - 36 - 37 4.0 38 ; 39 leg 38 ; 40 : 40 : 41 or 41 or 43 2.4 41 or 52 compared 42 = 43 2.4 43 2.4 47 ci 43 2.4 52 compared 44 , 47 ci 45 95 47 ci 46 % 47 ci 47 ci 49 - 47 ci 51 ] 48 1.2 49 - 49 - 50 4.8 52 compared 53 with 53 with 57 tertiles 54 the 55 highest 54 the 57 tertiles 56 respective 57 tertiles those in the highest tertile of vat had 2.1 - fold higher odds of death ( 95 % ci 1.1 - 4.0 ) compared with the lowest vat tertile . 0 ###LEFT-WALL### 1 those 0 ###LEFT-WALL### 8 had 0 ###LEFT-WALL### 10 - 0 ###LEFT-WALL### 30 . 1 those 2 in 1 those 8 had 2 in 5 tertile 3 the 4 highest 3 the 5 tertile 5 tertile 6 of 6 of 7 vat 8 had 9 2.1 10 - 13 odds 11 fold 13 odds 12 higher 13 odds 13 odds 14 of 13 odds 24 compared 13 odds 25 with 14 of 15 death 15 death 19 ci 16 ( 19 ci 17 95 19 ci 18 % 19 ci 19 ci 21 - 19 ci 23 ) 20 1.1 21 - 21 - 22 4.0 25 with 29 tertile 26 the 27 lowest 26 the 29 tertile 28 vat 29 tertile conclusion : lower muscle [mass] and central adiposity appear to be important risk factors for mortality in hiv - infected individuals . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 2 : 6 and 2 : 9 appear 2 : 19 - 3 lower 4 muscle 4 muscle 6 and 6 and 8 adiposity 6 and 9 appear 7 central 8 adiposity 9 appear 10 to 9 appear 11 be 10 to 11 be 11 be 14 factors 12 important 14 factors 13 risk 14 factors 14 factors 15 for 15 for 16 mortality 16 mortality 17 in 17 in 18 hiv 19 - 21 individuals 19 - 22 . 20 infected 21 individuals a substantial proportion of this risk may be unrecognized because of the current reliance [on] body mass index in clinical practice . 0 ###LEFT-WALL### 3 proportion 0 ###LEFT-WALL### 8 be 0 ###LEFT-WALL### 22 . 1 a 2 substantial 1 a 3 proportion 2 substantial 3 proportion 3 proportion 4 of 3 proportion 7 may 4 of 6 risk 5 this 6 risk 7 may 8 be 8 be 9 unrecognized 9 unrecognized 10 because 9 unrecognized 19 in 10 because 11 of 11 of 18 index 12 the 18 index 13 current 14 reliance 14 reliance 18 index 16 body 18 index 17 mass 18 index 19 in 21 practice 20 clinical 21 practice none background : an excessive amount of adipose tissue may contribute to sarcopenia and may be one mechanism underlying accelerated loss of muscle mass [and] strength with aging . 0 ###LEFT-WALL### 1 none 0 ###LEFT-WALL### 24 mass 0 ###LEFT-WALL### 29 . 1 none 2 background 1 none 14 and 1 none 24 mass 2 background 3 : 3 : 9 tissue 4 an 5 excessive 4 an 6 amount 5 excessive 6 amount 6 amount 7 of 6 amount 9 tissue 7 of 9 tissue 8 adipose 9 tissue 9 tissue 14 and 10 may 11 contribute 10 may 14 and 11 contribute 12 to 12 to 13 sarcopenia 14 and 15 may 15 may 16 be 16 be 18 mechanism 17 one 18 mechanism 18 mechanism 19 underlying 18 mechanism 22 of 19 underlying 21 loss 20 accelerated 21 loss 22 of 23 muscle 24 mass 26 strength 24 mass 27 with 27 with 28 aging we therefore examined the association of baseline total body fat with changes in leg lean [mass] , muscle strength , and muscle quality over 7 years of [follow] - up and whether this link was explained by adipocytokines and insulin resistance . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 examined 0 ###LEFT-WALL### 36 explained 1 we 3 examined 2 therefore 3 examined 3 examined 21 and 3 examined 36 explained 4 the 5 association 5 association 6 of 5 association 11 with 5 association 17 , 6 of 10 fat 7 baseline 8 total 8 total 10 fat 9 body 10 fat 11 with 12 changes 12 changes 13 in 13 in 15 lean 14 leg 15 lean 17 , 19 strength 17 , 21 and 18 muscle 19 strength 20 , 21 and 21 and 23 quality 21 and 24 over 21 and 36 explained 22 muscle 23 quality 24 over 31 and 25 7 26 years 26 years 27 of 26 years 31 and 27 of 30 up 29 - 30 up 31 and 32 whether 31 and 34 link 31 and 35 was 33 this 34 link 34 link 35 was 36 explained 37 by 36 explained 42 . 37 by 39 and 38 adipocytokines 39 and 39 and 41 resistance 40 insulin 41 resistance methods : data were from 2,307 men and women , aged 70 - 79 years , participating in the health , aging , and body composition study . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 28 . 2 : 3 data 2 : 4 were 2 : 8 and 3 data 4 were 4 were 5 from 5 from 7 men 6 2,307 7 men 8 and 24 and 8 and 27 study 9 women 10 , 10 , 15 years 10 , 24 and 11 aged 15 years 12 70 13 - 13 - 14 79 13 - 15 years 15 years 17 participating 16 , 17 participating 17 participating 18 in 17 participating 23 , 18 in 20 health 19 the 20 health 20 health 22 aging 21 , 22 aging 22 aging 23 , 24 and 26 composition 24 and 27 study 25 body 26 composition total fat [mass] was acquired from dual energy x - ray absorptiometry . 0 ###LEFT-WALL### 2 fat 0 ###LEFT-WALL### 10 - 0 ###LEFT-WALL### 13 . 1 total 2 fat 2 fat 4 was 4 was 5 acquired 5 acquired 6 from 6 from 8 energy 7 dual 8 energy 8 energy 9 x 9 x 10 - 10 - 11 ray 11 ray 12 absorptiometry leg lean [mass] was assessed by dual energy x - ray absorptiometry in years 1 , 2 , 3 , 4 , 5 , 6 , [and] 8 . 0 ###LEFT-WALL### 2 lean 0 ###LEFT-WALL### 5 assessed 0 ###LEFT-WALL### 16 , 0 ###LEFT-WALL### 29 . 1 leg 2 lean 2 lean 4 was 4 was 5 assessed 5 assessed 6 by 6 by 8 energy 7 dual 8 energy 8 energy 9 x 8 energy 12 absorptiometry 10 - 12 absorptiometry 11 ray 12 absorptiometry 12 absorptiometry 13 in 12 absorptiometry 16 , 13 in 14 years 14 years 15 1 16 , 17 2 16 , 18 , 18 , 19 3 18 , 20 , 20 , 21 4 20 , 22 , 22 , 23 5 22 , 24 , 24 , 25 6 24 , 26 , 26 , 28 8 knee extension strength was measured by isokinetic dynamometer in years 1 , 2 , 4 , 6 , [and] 8 . 0 ###LEFT-WALL### 3 strength 0 ###LEFT-WALL### 4 was 0 ###LEFT-WALL### 14 , 0 ###LEFT-WALL### 21 . 1 knee 3 strength 2 extension 3 strength 3 strength 4 was 4 was 5 measured 5 measured 6 by 5 measured 9 in 6 by 8 dynamometer 7 isokinetic 8 dynamometer 9 in 10 years 10 years 11 1 10 years 13 2 12 , 13 2 13 2 14 , 14 , 15 4 14 , 16 , 16 , 17 6 16 , 18 , 18 , 20 8 muscle quality was calculated as muscle strength divided by leg lean [mass] . 0 ###LEFT-WALL### 4 calculated 1 muscle 2 quality 1 muscle 3 was 1 muscle 4 calculated 2 quality 3 was 4 calculated 5 as 4 calculated 13 . 5 as 7 strength 6 muscle 7 strength 7 strength 8 divided 8 divided 9 by 9 by 11 lean 10 leg 11 lean results : every sd greater fat mass was related to 1.3 kg more leg lean mass [at] baseline in men and 1.5 [kg] in women ( [p] < [.] 01 ) . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 7 mass 2 : 9 related 2 : 32 . 3 every 7 mass 4 sd 7 mass 5 greater 6 fat 6 fat 7 mass 7 mass 8 was 8 was 9 related 9 related 10 to 9 related 19 in 10 to 18 baseline 11 1.3 12 kg 12 kg 13 more 13 more 18 baseline 14 leg 15 lean 15 lean 18 baseline 16 mass 18 baseline 19 in 21 and 20 men 21 and 21 and 25 women 21 and 30 01 22 1.5 24 in 24 in 25 women 26 ( 30 01 28 < 30 01 30 01 31 ) greater fat [mass] was also associated with a greater decline in leg lean [mass] in both men and women ( 0.02 kg/year , p < [.] 01 [ )(, which was not explained by higher levels of adipocytokines and insulin resistance . 0 ###LEFT-WALL### 2 fat 0 ###LEFT-WALL### 6 associated 0 ###LEFT-WALL### 29 )(, 0 ###LEFT-WALL### 42 . 1 greater 2 fat 2 fat 4 was 4 was 6 associated 5 also 6 associated 6 associated 7 with 6 associated 11 in 6 associated 25 < 7 with 10 decline 8 a 10 decline 9 greater 10 decline 11 in 13 lean 12 leg 13 lean 13 lean 15 in 15 in 18 and 16 both 18 and 17 men 18 and 18 and 19 women 18 and 22 kg/year 20 ( 22 kg/year 21 0.02 22 kg/year 22 kg/year 23 , 23 , 25 < 24 p 25 < 25 < 27 01 29 )(, 30 which 29 )(, 31 was 30 which 31 was 31 was 32 not 31 was 34 by 32 not 33 explained 34 by 39 and 35 higher 36 levels 36 levels 37 of 36 levels 39 and 37 of 38 adipocytokines 39 and 41 resistance 40 insulin 41 resistance larger fat [mass] was related to significantly greater muscle strength but significantly lower muscle quality at baseline ( [p] < [.] 01 ) . 0 ###LEFT-WALL### 2 fat 0 ###LEFT-WALL### 11 but 0 ###LEFT-WALL### 24 . 1 larger 2 fat 2 fat 4 was 4 was 11 but 5 related 6 to 5 related 11 but 6 to 10 strength 7 significantly 8 greater 8 greater 9 muscle 9 muscle 10 strength 11 but 13 lower 12 significantly 13 lower 13 lower 15 quality 13 lower 16 at 14 muscle 15 quality 16 at 17 baseline 17 baseline 22 01 18 ( 22 01 20 < 22 01 22 01 23 ) no significant differences in decline [of] muscle strength and quality were found . 0 ###LEFT-WALL### 3 differences 0 ###LEFT-WALL### 12 found 0 ###LEFT-WALL### 13 . 1 no 3 differences 2 significant 3 differences 3 differences 4 in 3 differences 11 were 4 in 9 and 5 decline 8 strength 7 muscle 8 strength 8 strength 9 and 9 and 10 quality 11 were 12 found conclusions : high fatness was associated with lower muscle quality , and it predicts accelerated loss of lean [mass] . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 20 . 2 : 4 fatness 2 : 6 associated 2 : 12 and 3 high 4 fatness 4 fatness 5 was 5 was 6 associated 6 associated 7 with 7 with 10 quality 8 lower 9 muscle 9 muscle 10 quality 11 , 12 and 12 and 13 it 12 and 14 predicts 13 it 14 predicts 14 predicts 16 loss 15 accelerated 16 loss 16 loss 17 of 17 of 18 lean prevention of greater fatness in old age may decrease the loss of lean [mass] and maintain muscle quality and thereby reducing disability and mobility impairments . 0 ###LEFT-WALL### 1 prevention 0 ###LEFT-WALL### 15 and 0 ###LEFT-WALL### 19 and 0 ###LEFT-WALL### 26 . 1 prevention 2 of 1 prevention 8 may 2 of 4 fatness 3 greater 4 fatness 4 fatness 5 in 5 in 7 age 6 old 7 age 8 may 15 and 9 decrease 11 loss 9 decrease 15 and 10 the 11 loss 11 loss 12 of 12 of 13 lean 15 and 16 maintain 15 and 18 quality 16 maintain 17 muscle 19 and 21 reducing 19 and 25 impairments 20 thereby 21 reducing 21 reducing 23 and 21 reducing 25 impairments 22 disability 23 and 23 and 24 mobility objective : to compare the prevalence of cupular and free - floating deposits in the semicircular canals between temporal bones of type 1 diabetes mellitus patients and normal controls . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 11 - 0 ###LEFT-WALL### 30 . 1 objective 2 : 2 : 3 to 2 : 4 compare 3 to 4 compare 4 compare 6 prevalence 5 the 6 prevalence 6 prevalence 7 of 7 of 9 and 8 cupular 9 and 9 and 10 free 11 - 12 floating 11 - 13 deposits 12 floating 13 deposits 13 deposits 14 in 13 deposits 18 between 13 deposits 27 and 14 in 17 canals 15 the 17 canals 16 semicircular 17 canals 18 between 20 bones 19 temporal 20 bones 20 bones 21 of 21 of 22 type 22 type 23 1 24 diabetes 26 patients 25 mellitus 26 patients 26 patients 27 and 27 and 29 controls 28 normal 29 controls study design : case - control histopathologic human temporal bone study . 0 ###LEFT-WALL### 2 design 0 ###LEFT-WALL### 3 : 0 ###LEFT-WALL### 5 - 1 study 2 design 2 design 3 : 3 : 4 case 5 - 6 control 5 - 12 . 6 control 11 study 7 histopathologic 8 human 8 human 11 study 9 temporal 10 bone 10 bone 11 study setting : otopathology [laboratory] in a tertiary academic medical center . 0 ###LEFT-WALL### 1 setting 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 11 . 1 setting 2 : 2 : 3 otopathology 3 otopathology 5 in 5 in 10 center 6 a 7 tertiary 6 a 10 center 7 tertiary 10 center 8 academic 10 center 9 medical 10 center subjects and methods : twenty - eight temporal bones from 14 patients with type 1 diabetes mellitus and 56 normal temporal bones from 28 age - matched individuals were histopathologically examined . 0 ###LEFT-WALL### 3 methods 0 ###LEFT-WALL### 4 : 0 ###LEFT-WALL### 26 - 1 subjects 2 and 2 and 3 methods 3 methods 4 : 4 : 9 bones 4 : 10 from 5 twenty 6 - 6 - 7 eight 6 - 9 bones 8 temporal 9 bones 10 from 12 patients 11 14 12 patients 12 patients 13 with 12 patients 18 and 12 patients 25 age 13 with 14 type 14 type 15 1 16 diabetes 17 mellitus 17 mellitus 18 and 18 and 22 bones 18 and 23 from 18 and 25 age 19 56 22 bones 20 normal 22 bones 21 temporal 22 bones 23 from 24 28 26 - 28 individuals 26 - 29 were 26 - 32 . 27 matched 28 individuals 28 individuals 29 were 29 were 30 histopathologically 29 were 31 examined the cupula and lumina of the semicircular canals were examined for evidence of deposits . 0 ###LEFT-WALL### 3 and 0 ###LEFT-WALL### 10 examined 0 ###LEFT-WALL### 15 . 1 the 2 cupula 2 cupula 3 and 3 and 4 lumina 3 and 5 of 3 and 9 were 5 of 8 canals 6 the 8 canals 7 semicircular 8 canals 9 were 10 examined 10 examined 11 for 11 for 12 evidence 12 evidence 13 of 13 of 14 deposits the prevalence of these deposits was associated with the duration of disease rather than with aging . 0 ###LEFT-WALL### 2 prevalence 0 ###LEFT-WALL### 7 associated 0 ###LEFT-WALL### 17 . 1 the 2 prevalence 2 prevalence 3 of 2 prevalence 6 was 3 of 5 deposits 4 these 5 deposits 6 was 7 associated 7 associated 8 with 7 associated 14 than 8 with 10 duration 9 the 10 duration 10 duration 11 of 11 of 12 disease 13 rather 14 than 14 than 15 with 15 with 16 aging conclusion : the findings suggest that type 1 diabetes mellitus is associated with cupular and free - floating deposits in the semicircular canals . 0 ###LEFT-WALL### 1 conclusion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 7 type 2 : 4 findings 2 : 5 suggest 3 the 4 findings 4 findings 5 suggest 5 suggest 6 that 5 suggest 7 type 7 type 9 diabetes 7 type 15 and 8 1 9 diabetes 9 diabetes 10 mellitus 9 diabetes 13 with 10 mellitus 11 is 11 is 12 associated 12 associated 13 with 14 cupular 15 and 15 and 16 free 16 free 18 floating 17 - 18 floating 18 floating 19 deposits 18 floating 20 in 18 floating 24 . 20 in 23 canals 21 the 23 canals 22 semicircular 23 canals the patients with [type] 1 diabetes mellitus with a longer duration of disease have an increased probability of suffering from benign paroxysmal positional vertigo . 0 ###LEFT-WALL### 2 patients 0 ###LEFT-WALL### 14 have 0 ###LEFT-WALL### 25 . 1 the 2 patients 2 patients 3 with 2 patients 14 have 3 with 7 mellitus 5 1 7 mellitus 6 diabetes 7 mellitus 7 mellitus 8 with 8 with 11 duration 9 a 11 duration 10 longer 11 duration 11 duration 12 of 12 of 13 disease 14 have 17 probability 15 an 17 probability 16 increased 17 probability 17 probability 18 of 18 of 19 suffering 19 suffering 20 from 20 from 24 vertigo 21 benign 24 vertigo 22 paroxysmal 24 vertigo 23 positional 24 vertigo type 2 diabetes is a metabolic disease that profoundly affects energy homeostasis . 0 ###LEFT-WALL### 3 diabetes 0 ###LEFT-WALL### 4 is 0 ###LEFT-WALL### 13 . 1 type 2 2 1 type 3 diabetes 3 diabetes 4 is 4 is 7 disease 5 a 6 metabolic 5 a 7 disease 6 metabolic 7 disease 7 disease 8 that 7 disease 10 affects 8 that 10 affects 9 profoundly 10 affects 10 affects 12 homeostasis 11 energy 12 homeostasis the disease involves failure at several levels and subsystems and is characterized by insulin resistance in target cells and tissues ( i.e [.] by impaired intracellular insulin signaling ) . 0 ###LEFT-WALL### 2 disease 0 ###LEFT-WALL### 8 and 0 ###LEFT-WALL### 30 . 1 the 2 disease 2 disease 8 and 3 involves 4 failure 3 involves 5 at 3 involves 8 and 5 at 7 levels 6 several 7 levels 8 and 10 and 9 subsystems 10 and 10 and 11 is 11 is 12 characterized 12 characterized 13 by 12 characterized 16 in 13 by 15 resistance 14 insulin 15 resistance 16 in 19 and 17 target 18 cells 18 cells 19 and 19 and 20 tissues 19 and 22 i.e 21 ( 22 i.e 22 i.e 24 by 22 i.e 29 ) 24 by 27 insulin 25 impaired 27 insulin 26 intracellular 27 insulin 27 insulin 28 signaling we have previously used an iterative experimental - theoretical approach to unravel the early insulin signaling events in primary human adipocytes . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 4 used 0 ###LEFT-WALL### 22 . 1 we 2 have 2 have 4 used 3 previously 4 used 4 used 10 approach 4 used 11 to 4 used 12 unravel 5 an 6 iterative 5 an 10 approach 6 iterative 10 approach 7 experimental 8 - 7 experimental 10 approach 9 theoretical 10 approach 11 to 12 unravel 12 unravel 15 insulin 13 the 15 insulin 14 early 15 insulin 15 insulin 16 signaling 16 signaling 17 events 16 signaling 18 in 18 in 21 adipocytes 19 primary 21 adipocytes 20 human 21 adipocytes that study , like most insulin signaling studies , is based on in vitro experimental examination of cells , and the [in] [vivo] relevance of such studies for human beings has not been systematically examined . 0 ###LEFT-WALL### 1 that 0 ###LEFT-WALL### 35 examined 0 ###LEFT-WALL### 36 . 1 that 2 study 1 that 11 based 1 that 31 has 2 study 4 like 2 study 10 is 3 , 4 like 4 like 6 insulin 4 like 9 , 5 most 6 insulin 6 insulin 7 signaling 7 signaling 8 studies 10 is 11 based 11 based 12 on 11 based 28 for 12 on 20 and 13 in 14 vitro 14 vitro 15 experimental 15 experimental 16 examination 16 examination 17 of 16 examination 20 and 17 of 18 cells 19 , 20 and 20 and 24 relevance 21 the 24 relevance 24 relevance 25 of 25 of 27 studies 26 such 27 studies 28 for 30 beings 29 human 30 beings 31 has 32 not 31 has 33 been 33 been 35 examined 34 systematically 35 examined herein , we develop a hierarchical model of the adipose tissue , which links intracellular insulin control of glucose transport in human primary adipocytes with whole - body glucose homeostasis . 0 ###LEFT-WALL### 1 herein 0 ###LEFT-WALL### 2 , 0 ###LEFT-WALL### 31 . 2 , 3 we 2 , 4 develop 2 , 12 , 3 we 4 develop 4 develop 7 model 5 a 6 hierarchical 5 a 7 model 6 hierarchical 7 model 7 model 8 of 8 of 11 tissue 9 the 11 tissue 10 adipose 11 tissue 12 , 13 which 12 , 14 links 13 which 14 links 14 links 17 control 14 links 21 in 14 links 25 with 15 intracellular 16 insulin 16 insulin 17 control 17 control 18 of 18 of 20 transport 19 glucose 20 transport 21 in 24 adipocytes 22 human 23 primary 23 primary 24 adipocytes 25 with 30 homeostasis 26 whole 27 - 26 whole 28 body 28 body 29 glucose 29 glucose 30 homeostasis an iterative approach between experiments and minimal modeling allowed us to conclude that it is not possible to scale up the experimentally determined glucose uptake by the isolated adipocytes to match the glucose uptake profile of the adipose tissue in vivo . 0 ###LEFT-WALL### 3 approach 0 ###LEFT-WALL### 9 allowed 0 ###LEFT-WALL### 42 . 1 an 2 iterative 1 an 3 approach 2 iterative 3 approach 3 approach 4 between 3 approach 9 allowed 4 between 6 and 5 experiments 6 and 6 and 8 modeling 7 minimal 8 modeling 9 allowed 10 us 9 allowed 11 to 9 allowed 18 to 9 allowed 19 scale 11 to 12 conclude 12 conclude 13 that 13 that 14 it 13 that 15 is 14 it 15 is 15 is 16 not 15 is 17 possible 18 to 19 scale 19 scale 20 up 19 scale 24 glucose 21 the 24 glucose 22 experimentally 23 determined 23 determined 24 glucose 24 glucose 25 uptake 24 glucose 29 adipocytes 25 uptake 26 by 25 uptake 29 adipocytes 26 by 28 isolated 27 the 28 isolated 29 adipocytes 30 to 30 to 31 match 31 match 35 profile 31 match 41 vivo 32 the 35 profile 33 glucose 34 uptake 34 uptake 35 profile 35 profile 36 of 36 of 39 tissue 37 the 39 tissue 38 adipose 39 tissue 40 in 41 vivo however , a model that additionally includes insulin effects on blood flow in the adipose tissue and glut4 translocation due to cell handling can explain all data , but neither of these additions is sufficient independently . 0 ###LEFT-WALL### 4 model 0 ###LEFT-WALL### 25 explain 0 ###LEFT-WALL### 29 but 0 ###LEFT-WALL### 37 . 1 however 2 , 1 however 4 model 3 a 4 model 4 model 5 that 4 model 7 includes 4 model 24 can 5 that 7 includes 6 additionally 7 includes 7 includes 9 effects 7 includes 21 to 8 insulin 9 effects 9 effects 10 on 10 on 17 and 11 blood 12 flow 12 flow 13 in 12 flow 17 and 13 in 16 tissue 14 the 16 tissue 15 adipose 16 tissue 17 and 19 translocation 18 glut4 19 translocation 20 due 21 to 21 to 23 handling 22 cell 23 handling 24 can 25 explain 25 explain 27 data 26 all 27 data 28 , 29 but 29 but 30 neither 29 but 34 is 30 neither 31 of 30 neither 34 is 31 of 33 additions 32 these 33 additions 34 is 35 sufficient 35 sufficient 36 independently we also extend the minimal model to include hierarchical dynamic links to more detailed models ( both to our own models and to those by others ) , which act as submodules that can be turned on [or] off . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 extend 0 ###LEFT-WALL### 28 , 0 ###LEFT-WALL### 40 . 1 we 3 extend 2 also 3 extend 3 extend 6 model 3 extend 7 to 3 extend 12 to 4 the 6 model 5 minimal 6 model 7 to 8 include 8 include 11 links 9 hierarchical 10 dynamic 10 dynamic 11 links 12 to 15 models 13 more 15 models 14 detailed 15 models 15 models 17 both 16 ( 17 both 17 both 22 and 17 both 27 ) 18 to 21 models 18 to 22 and 19 our 20 own 19 our 21 models 22 and 23 to 23 to 24 those 24 those 25 by 25 by 26 others 28 , 29 which 28 , 30 act 29 which 30 act 30 act 31 as 31 as 32 submodules 32 submodules 33 that 32 submodules 39 off 33 that 34 can 34 can 35 be 35 be 36 turned 36 turned 37 on 36 turned 39 off the resulting multilevel hierarchical model can merge detailed results on different subsystems into a coherent understanding of whole - body glucose homeostasis . 0 ###LEFT-WALL### 5 model 0 ###LEFT-WALL### 7 merge 0 ###LEFT-WALL### 23 . 1 the 5 model 2 resulting 5 model 3 multilevel 5 model 4 hierarchical 5 model 5 model 6 can 6 can 7 merge 7 merge 9 results 7 merge 10 on 7 merge 13 into 8 detailed 9 results 10 on 12 subsystems 11 different 12 subsystems 13 into 16 understanding 14 a 15 coherent 14 a 16 understanding 15 coherent 16 understanding 16 understanding 17 of 17 of 22 homeostasis 18 whole 19 - 18 whole 20 body 20 body 21 glucose 21 glucose 22 homeostasis this hierarchical modeling can potentially create bridges between other experimental model systems and the in vivo human situation and offers a framework [for] systematic evaluation of the physiological relevance of in vitro obtained molecular/cellular experimental data . 0 ###LEFT-WALL### 3 modeling 0 ###LEFT-WALL### 19 and 0 ###LEFT-WALL### 37 . 1 this 2 hierarchical 2 hierarchical 3 modeling 3 modeling 19 and 4 can 6 create 4 can 19 and 5 potentially 6 create 6 create 7 bridges 6 create 8 between 8 between 13 and 9 other 12 systems 10 experimental 11 model 11 model 12 systems 12 systems 13 and 13 and 18 situation 14 the 18 situation 15 in 16 vivo 16 vivo 17 human 17 human 18 situation 19 and 20 offers 19 and 25 evaluation 21 a 25 evaluation 22 framework 25 evaluation 24 systematic 25 evaluation 25 evaluation 26 of 25 evaluation 30 of 26 of 29 relevance 27 the 29 relevance 28 physiological 29 relevance 30 of 36 data 31 in 32 vitro 32 vitro 33 obtained 33 obtained 36 data 34 molecular/cellular 36 data 35 experimental 36 data radiation therapy remains a promising modality for curative treatment of localized prostate cancer , but [dose] - limiting toxicities significantly limit its effectiveness . 0 ###LEFT-WALL### 2 therapy 0 ###LEFT-WALL### 3 remains 0 ###LEFT-WALL### 15 but 0 ###LEFT-WALL### 24 . 1 radiation 2 therapy 2 therapy 3 remains 3 remains 6 modality 3 remains 7 for 4 a 6 modality 5 promising 6 modality 7 for 9 treatment 8 curative 9 treatment 9 treatment 10 of 10 of 13 cancer 11 localized 12 prostate 12 prostate 13 cancer 14 , 15 but 15 but 17 - 15 but 21 limit 17 - 19 toxicities 18 limiting 19 toxicities 19 toxicities 21 limit 20 significantly 21 limit 21 limit 23 effectiveness 22 its 23 effectiveness agents that enhance efficacy at lower radiation doses might have considerable value in increasing tumor control without compromising organ function . 0 ###LEFT-WALL### 1 agents 0 ###LEFT-WALL### 10 have 0 ###LEFT-WALL### 21 . 1 agents 2 that 1 agents 3 enhance 1 agents 9 might 2 that 3 enhance 3 enhance 4 efficacy 3 enhance 5 at 5 at 8 doses 6 lower 7 radiation 7 radiation 8 doses 9 might 10 have 10 have 12 value 10 have 13 in 10 have 17 without 10 have 20 function 11 considerable 12 value 13 in 14 increasing 14 increasing 16 control 15 tumor 16 control 17 without 19 organ 18 compromising 19 organ here , we tested the hypothesis that the parp inhibitor abt - 888 ( veliparib ) can enhance the response of prostate cancer cells and tumors to ionizing radiation ( ir ) . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 tested 0 ###LEFT-WALL### 33 . 1 here 2 , 1 here 3 we 3 we 4 tested 4 tested 6 hypothesis 4 tested 27 to 5 the 6 hypothesis 6 hypothesis 7 that 7 that 11 abt 7 that 18 enhance 8 the 10 inhibitor 9 parp 10 inhibitor 10 inhibitor 11 abt 11 abt 13 888 11 abt 17 can 12 - 13 888 13 888 15 veliparib 13 888 16 ) 14 ( 15 veliparib 15 veliparib 16 ) 17 can 18 enhance 18 enhance 20 response 19 the 20 response 20 response 21 of 21 of 25 and 22 prostate 24 cells 23 cancer 24 cells 24 cells 25 and 25 and 26 tumors 27 to 28 ionizing 28 ionizing 29 radiation 29 radiation 31 ir 30 ( 31 ir 31 ir 32 ) following exposure of du - 145 and pc - 3 prostate cancer cell lines to the combination of 10 μmol/l abt - 888 and 6 gy , we observed similar persistence between both cell lines of dna damage foci and in [vitro] radiosensitization . 0 ###LEFT-WALL### 14 lines 0 ###LEFT-WALL### 20 μmol/l 0 ###LEFT-WALL### 27 , 0 ###LEFT-WALL### 44 . 1 following 2 exposure 1 following 9 - 1 following 14 lines 2 exposure 3 of 2 exposure 8 pc 3 of 4 du 5 - 8 pc 6 145 7 and 7 and 8 pc 8 pc 9 - 10 3 14 lines 11 prostate 14 lines 12 cancer 14 lines 13 cell 14 lines 14 lines 15 to 14 lines 18 of 14 lines 20 μmol/l 15 to 17 combination 16 the 17 combination 18 of 19 10 20 μmol/l 26 gy 21 abt 24 and 21 abt 26 gy 22 - 23 888 23 888 24 and 24 and 25 6 27 , 28 we 27 , 29 observed 28 we 29 observed 29 observed 31 persistence 29 observed 40 and 30 similar 31 persistence 32 between 35 lines 32 between 40 and 33 both 35 lines 34 cell 35 lines 35 lines 36 of 36 of 39 foci 37 dna 39 foci 38 damage 39 foci 40 and 41 in 41 in 43 radiosensitization we have previously observed that persistent dna damage foci formed after abt - 888 plus ir efficiently promote accelerated cell senescence , but only pc - 3 cells displayed the expected senescent response of g ( 2 ) - [m] arrest , induction of p21 and β - galactosidase expression , and accumulation as large flat cells . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 13 - 0 ###LEFT-WALL### 58 . 1 we 2 have 2 have 9 foci 2 have 10 formed 3 previously 4 observed 4 observed 9 foci 5 that 6 persistent 6 persistent 9 foci 7 dna 9 foci 8 damage 9 foci 10 formed 11 after 11 after 12 abt 13 - 14 888 13 - 18 promote 13 - 22 , 14 888 15 plus 14 888 18 promote 15 plus 16 ir 17 efficiently 18 promote 18 promote 21 senescence 19 accelerated 20 cell 20 cell 21 senescence 22 , 28 cells 22 , 29 displayed 22 , 39 - 23 but 24 only 23 but 28 cells 25 pc 26 - 25 pc 28 cells 27 3 28 cells 28 cells 29 displayed 29 displayed 33 response 30 the 33 response 31 expected 33 response 32 senescent 33 response 33 response 34 of 33 response 37 2 34 of 35 g 36 ( 37 2 37 2 38 ) 39 - 46 and 39 - 48 - 41 arrest 42 , 42 , 43 induction 42 , 46 and 43 induction 44 of 44 of 45 p21 46 and 47 β 48 - 52 and 49 galactosidase 50 expression 50 expression 52 and 51 , 52 and 52 and 53 accumulation 53 accumulation 54 as 54 as 57 cells 55 large 57 cells 56 flat 57 cells in turn , combining abt - 888 with 6 gy resulted in delayed tumor regrowth compared with either agent alone only in pc - 3 xenograft tumors , whereas du - 145 tumors continued to grow . 0 ###LEFT-WALL### 7 888 0 ###LEFT-WALL### 13 delayed 0 ###LEFT-WALL### 24 - 0 ###LEFT-WALL### 34 continued 0 ###LEFT-WALL### 37 . 1 in 2 turn 2 turn 3 , 2 turn 7 888 3 , 4 combining 4 combining 5 abt 4 combining 6 - 4 combining 7 888 7 888 8 with 7 888 10 gy 7 888 12 in 7 888 13 delayed 8 with 9 6 10 gy 11 resulted 11 resulted 12 in 13 delayed 15 regrowth 14 tumor 15 regrowth 15 regrowth 16 compared 16 compared 17 with 16 compared 22 in 17 with 19 agent 17 with 20 alone 18 either 19 agent 20 alone 21 only 22 in 23 pc 24 - 25 3 24 - 26 xenograft 25 3 26 xenograft 26 xenograft 27 tumors 26 xenograft 29 whereas 28 , 29 whereas 29 whereas 33 tumors 30 du 31 - 30 du 33 tumors 32 145 33 tumors 33 tumors 34 continued 34 continued 35 to 35 to 36 grow by 7 days after treatment with abt - 888 plus ir , pc - 3 tumors contained abundant senescent cells displaying persistent dna damage foci , but no evidence of senescence was noted in the du - 145 tumors . 0 ###LEFT-WALL### 16 tumors 0 ###LEFT-WALL### 19 senescent 0 ###LEFT-WALL### 27 but 1 by 3 days 1 by 14 - 1 by 16 tumors 2 7 3 days 3 days 4 after 4 after 5 treatment 5 treatment 6 with 5 treatment 11 ir 6 with 7 abt 8 - 11 ir 9 888 11 ir 10 plus 11 ir 11 ir 13 pc 11 ir 14 - 12 , 13 pc 13 pc 14 - 15 3 16 tumors 16 tumors 17 contained 16 tumors 19 senescent 17 contained 18 abundant 19 senescent 20 cells 20 cells 21 displaying 21 displaying 25 foci 22 persistent 24 damage 23 dna 24 damage 24 damage 25 foci 26 , 27 but 27 but 29 evidence 27 but 33 noted 28 no 29 evidence 29 evidence 30 of 29 evidence 32 was 30 of 31 senescence 32 was 33 noted 33 noted 34 in 34 in 36 du 35 the 36 du 36 du 39 tumors 37 - 39 tumors 38 145 39 tumors 39 tumors 40 . that equivalent radiosensitization by abt - 888 plus ir in vitro failed to predict comparable results with tumors in vivo suggests that the efficacy of parp inhibitors may partially depend on a competent senescence response to accumulated dna damage . 0 ###LEFT-WALL### 3 radiosensitization 0 ###LEFT-WALL### 21 suggests 0 ###LEFT-WALL### 40 . 1 that 3 radiosensitization 2 equivalent 3 radiosensitization 3 radiosensitization 4 by 3 radiosensitization 9 ir 3 radiosensitization 14 predict 3 radiosensitization 21 suggests 4 by 5 abt 6 - 7 888 7 888 9 ir 8 plus 9 ir 9 ir 12 failed 10 in 11 vitro 11 vitro 12 failed 12 failed 13 to 12 failed 14 predict 13 to 14 predict 14 predict 16 results 14 predict 17 with 14 predict 20 vivo 15 comparable 16 results 17 with 18 tumors 19 in 20 vivo 21 suggests 22 that 22 that 24 efficacy 22 that 37 accumulated 23 the 24 efficacy 24 efficacy 25 of 24 efficacy 37 accumulated 25 of 26 parp 26 parp 27 inhibitors 26 parp 36 to 27 inhibitors 28 may 28 may 30 depend 29 partially 30 depend 30 depend 31 on 30 depend 36 to 31 on 35 response 32 a 33 competent 32 a 35 response 33 competent 34 senescence 34 senescence 35 response 37 accumulated 39 damage 38 dna 39 damage objectives : to investigate age differences in working memory processing , specifically the accuracy of retrieval of items stored outside the immediate focus of attention . 0 ###LEFT-WALL### 1 objectives 0 ###LEFT-WALL### 2 : 2 : 3 to 2 : 4 investigate 2 : 11 , 2 : 26 . 3 to 4 investigate 4 investigate 6 differences 4 investigate 7 in 5 age 6 differences 7 in 8 working 8 working 10 processing 9 memory 10 processing 11 , 14 accuracy 11 , 19 stored 12 specifically 14 accuracy 13 the 14 accuracy 14 accuracy 15 of 14 accuracy 17 of 14 accuracy 19 stored 15 of 16 retrieval 17 of 18 items 19 stored 20 outside 19 stored 23 focus 21 the 23 focus 22 immediate 23 focus 23 focus 24 of 24 of 25 attention methods : younger and older adults were tested on a modified n - back task with probes presented in an unpredictable order ( implying also that some trials necessitated a switch in the focus of attention and others that did not ) . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 43 . 2 : 6 adults 2 : 8 tested 2 : 13 - 3 younger 4 and 4 and 5 older 4 and 6 adults 6 adults 7 were 7 were 8 tested 8 tested 9 on 9 on 12 n 10 a 12 n 11 modified 12 n 13 - 15 task 14 back 15 task 15 task 16 with 15 task 19 in 16 with 17 probes 17 probes 18 presented 19 in 22 order 20 an 21 unpredictable 20 an 22 order 21 unpredictable 22 order 22 order 24 implying 23 ( 24 implying 24 implying 25 also 24 implying 26 that 24 implying 42 ) 26 that 28 trials 26 that 29 necessitated 27 some 28 trials 28 trials 29 necessitated 29 necessitated 31 switch 29 necessitated 32 in 30 a 31 switch 32 in 34 focus 33 the 34 focus 34 focus 35 of 35 of 37 and 36 attention 37 and 37 and 38 others 37 and 39 that 37 and 40 did 39 that 40 did 40 did 41 not results : older adults showed intact item accessibility , that is , after taking general slowing into account , older adults were as fast as younger adults in locating the item in working memory . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 35 . 2 : 4 adults 2 : 5 showed 3 older 4 adults 4 adults 5 showed 5 showed 8 accessibility 5 showed 11 is 5 showed 21 adults 5 showed 22 were 6 intact 7 item 7 item 8 accessibility 9 , 11 is 10 that 11 is 11 is 12 , 12 , 13 after 13 after 14 taking 13 after 19 , 13 after 21 adults 14 taking 15 general 15 general 16 slowing 16 slowing 18 account 17 into 18 account 20 older 21 adults 21 adults 22 were 22 were 24 fast 22 were 25 as 22 were 28 in 23 as 24 fast 25 as 27 adults 26 younger 27 adults 28 in 29 locating 29 locating 31 item 29 locating 32 in 30 the 31 item 32 in 33 working 33 working 34 memory we found age differences , however , in item availability : older adults were less likely to correctly retrieve items stored outside the focus of attention . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 found 0 ###LEFT-WALL### 11 : 0 ###LEFT-WALL### 27 . 1 we 2 found 2 found 3 age 2 found 4 differences 2 found 6 however 2 found 8 in 5 , 6 however 6 however 7 , 7 , 8 in 8 in 10 availability 8 in 11 : 9 item 10 availability 11 : 13 adults 11 : 14 were 12 older 13 adults 13 adults 14 were 14 were 16 likely 15 less 16 likely 16 likely 17 to 16 likely 19 retrieve 17 to 19 retrieve 18 correctly 19 retrieve 19 retrieve 20 items 19 retrieve 22 outside 20 items 21 stored 22 outside 24 focus 23 the 24 focus 24 focus 25 of 25 of 26 attention smaller age differences in availability were also found for items stored inside the focus of attention . 0 ###LEFT-WALL### 3 differences 0 ###LEFT-WALL### 8 found 0 ###LEFT-WALL### 17 . 1 smaller 2 age 2 age 3 differences 3 differences 4 in 3 differences 6 were 4 in 5 availability 6 were 8 found 7 also 8 found 8 found 9 for 9 for 10 items 10 items 11 stored 11 stored 12 inside 12 inside 14 focus 13 the 14 focus 14 focus 15 of 15 of 16 attention discussion : these results strongly suggest that item availability is a cognitive primitive that is not reducible to more basic constructs such as item accessibility or simple speed of processing . 0 ###LEFT-WALL### 1 discussion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 31 . 2 : 10 is 3 these 4 results 4 results 6 suggest 5 strongly 6 suggest 6 suggest 7 that 7 that 9 availability 7 that 10 is 8 item 9 availability 10 is 13 primitive 10 is 21 constructs 11 a 12 cognitive 11 a 13 primitive 12 cognitive 13 primitive 13 primitive 14 that 13 primitive 15 is 14 that 15 is 15 is 16 not 15 is 17 reducible 17 reducible 18 to 18 to 19 more 20 basic 21 constructs 21 constructs 23 as 21 constructs 29 of 22 such 23 as 23 as 26 or 24 item 25 accessibility 25 accessibility 26 or 26 or 28 speed 27 simple 28 speed 29 of 30 processing objectives : research on age stereotypes suggests that views of older persons are complex and multidimensional . 0 ###LEFT-WALL### 1 objectives 0 ###LEFT-WALL### 2 : 2 : 3 research 2 : 7 suggests 2 : 17 . 3 research 4 on 3 research 7 suggests 4 on 6 stereotypes 5 age 6 stereotypes 7 suggests 8 that 8 that 9 views 8 that 13 are 9 views 10 of 9 views 13 are 10 of 12 persons 11 older 12 persons 13 are 15 and 14 complex 15 and 15 and 16 multidimensional we investigated the positivity or negativity of age stereotypes with respect to different life domains . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 investigated 0 ###LEFT-WALL### 16 . 1 we 2 investigated 2 investigated 5 or 2 investigated 10 with 3 the 4 positivity 4 positivity 5 or 5 or 6 negativity 5 or 7 of 7 of 9 stereotypes 8 age 9 stereotypes 10 with 11 respect 11 respect 12 to 12 to 15 domains 13 different 14 life 14 life 15 domains method : a newly developed questionnaire assessing domain [-] specific age stereotypes was administered to a large sample of adults covering a wide age range . 0 ###LEFT-WALL### 1 method 0 ###LEFT-WALL### 21 covering 0 ###LEFT-WALL### 26 . 1 method 2 : 2 : 6 questionnaire 3 a 6 questionnaire 4 newly 5 developed 5 developed 6 questionnaire 6 questionnaire 7 assessing 6 questionnaire 21 covering 7 assessing 12 stereotypes 7 assessing 13 was 8 domain 12 stereotypes 10 specific 11 age 11 age 12 stereotypes 13 was 14 administered 14 administered 15 to 15 to 18 sample 16 a 18 sample 17 large 18 sample 18 sample 19 of 18 sample 21 covering 19 of 20 adults 21 covering 25 range 22 a 23 wide 22 a 25 range 23 wide 24 age 24 age 25 range results : our findings confirm the existence of independent [domain] - specific age stereotypes , providing evidence for a multifaceted and complex view of old age and aging . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 29 . 2 : 4 findings 2 : 5 confirm 3 our 4 findings 4 findings 5 confirm 5 confirm 7 existence 6 the 7 existence 7 existence 8 of 8 of 17 evidence 9 independent 14 stereotypes 9 independent 17 evidence 11 - 14 stereotypes 12 specific 13 age 13 age 14 stereotypes 14 stereotypes 15 , 16 providing 17 evidence 17 evidence 18 for 17 evidence 24 of 18 for 23 view 19 a 23 view 20 multifaceted 21 and 21 and 22 complex 21 and 23 view 24 of 27 and 25 old 26 age 26 age 27 and 27 and 28 aging " old persons " were evaluated differently in the various life domains , and age thresholds for ascriptions of being old differed between domains . 0 ###LEFT-WALL### 1 " 0 ###LEFT-WALL### 3 persons 0 ###LEFT-WALL### 6 evaluated 0 ###LEFT-WALL### 14 and 0 ###LEFT-WALL### 25 . 2 old 3 persons 3 persons 4 " 3 persons 5 were 5 were 6 evaluated 6 evaluated 7 differently 7 differently 8 in 8 in 12 domains 9 the 12 domains 10 various 11 life 11 life 12 domains 13 , 14 and 14 and 16 thresholds 14 and 22 differed 15 age 16 thresholds 16 thresholds 17 for 16 thresholds 22 differed 17 for 18 ascriptions 18 ascriptions 19 of 19 of 20 being 20 being 21 old 22 differed 23 between 23 between 24 domains furthermore , the positivity of domain [-] specific age stereotypes of a person predicted individual life satisfaction for the respective life domain . 0 ###LEFT-WALL### 4 positivity 0 ###LEFT-WALL### 14 predicted 0 ###LEFT-WALL### 23 . 1 furthermore 2 , 1 furthermore 4 positivity 3 the 4 positivity 4 positivity 5 of 4 positivity 14 predicted 5 of 10 stereotypes 6 domain 10 stereotypes 8 specific 9 age 9 age 10 stereotypes 10 stereotypes 11 of 11 of 13 person 12 a 13 person 14 predicted 17 satisfaction 15 individual 17 satisfaction 16 life 17 satisfaction 17 satisfaction 18 for 18 for 22 domain 19 the 22 domain 20 respective 21 life 21 life 22 domain the strength of the relationship between age stereotypes and life satisfaction increased with participants ' age . 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 17 . 1 the 2 strength 2 strength 3 of 2 strength 9 and 3 of 5 relationship 4 the 5 relationship 5 relationship 6 between 6 between 8 stereotypes 7 age 8 stereotypes 9 and 11 satisfaction 9 and 12 increased 10 life 11 satisfaction 12 increased 13 with 13 with 16 age 14 participants 15 ' 15 ' 16 age discussion : our results indicate the existence [of] domain - specific age stereotypes that become internalized into older persons ' self - views . 0 ###LEFT-WALL### 1 discussion 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 24 . 2 : 4 results 2 : 5 indicate 2 : 22 - 3 our 4 results 4 results 5 indicate 5 indicate 9 domain 6 the 9 domain 7 existence 9 domain 9 domain 13 stereotypes 10 - 13 stereotypes 11 specific 13 stereotypes 12 age 13 stereotypes 13 stereotypes 14 that 13 stereotypes 15 become 13 stereotypes 22 - 14 that 15 become 15 become 16 internalized 16 internalized 17 into 17 into 21 self 18 older 19 persons 19 persons 20 ' 20 ' 21 self 22 - 23 views helicases must unwind dna at the right place and time to maintain genomic integrity or gene expression . 0 ###LEFT-WALL### 1 helicases 0 ###LEFT-WALL### 9 and 0 ###LEFT-WALL### 18 . 1 helicases 9 and 2 must 3 unwind 2 must 9 and 3 unwind 4 dna 3 unwind 5 at 5 at 8 place 6 the 8 place 7 right 8 place 9 and 10 time 9 and 11 to 11 to 12 maintain 12 maintain 15 or 13 genomic 14 integrity 14 integrity 15 or 15 or 17 expression 16 gene 17 expression biologically critical xpb and xpd helicases are key members of the human tfiih complex ; they anchor cak [kinase] ( cyclinh , mat1 , cdk7 ) to tfiih and open dna for transcription and for repair of [duplex] distorting damage by nucleotide excision repair ( ner ) . 0 ###LEFT-WALL### 6 helicases 0 ###LEFT-WALL### 8 key 0 ###LEFT-WALL### 15 ; 0 ###LEFT-WALL### 17 anchor 0 ###LEFT-WALL### 48 . 1 biologically 2 critical 2 critical 3 xpb 3 xpb 4 and 4 and 5 xpd 4 and 6 helicases 6 helicases 7 are 7 are 8 key 8 key 9 members 9 members 10 of 10 of 14 complex 11 the 14 complex 12 human 14 complex 13 tfiih 14 complex 15 ; 16 they 16 they 17 anchor 17 anchor 18 cak 17 anchor 27 to 17 anchor 34 and 17 anchor 41 by 18 cak 25 cdk7 20 ( 25 cdk7 21 cyclinh 23 mat1 21 cyclinh 24 , 21 cyclinh 25 cdk7 22 , 23 mat1 23 mat1 24 , 25 cdk7 26 ) 27 to 29 and 28 tfiih 29 and 29 and 31 dna 30 open 31 dna 32 for 33 transcription 32 for 34 and 34 and 35 for 35 for 36 repair 36 repair 37 of 37 of 39 distorting 39 distorting 40 damage 41 by 44 repair 42 nucleotide 43 excision 43 excision 44 repair 44 repair 46 ner 45 ( 46 ner 46 ner 47 ) ner is initiated by arrested rna [polymerase] or damage recognition by xpc - [rad23b] [with] or without ddb1/ddb2 . 0 ###LEFT-WALL### 1 ner 0 ###LEFT-WALL### 3 initiated 0 ###LEFT-WALL### 19 . 1 ner 2 is 2 is 3 initiated 3 initiated 4 by 4 by 8 or 5 arrested 6 rna 6 rna 8 or 8 or 10 recognition 8 or 16 or 9 damage 10 recognition 11 by 12 xpc 11 by 16 or 13 - 16 or 16 or 17 without 17 without 18 ddb1/ddb2 xp helicases , named for their role in the extreme sun - mediated skin cancer predisposition xeroderma pigmentosum ( xp ) , are then recruited to asymmetrically [unwind] [dsdna] flanking the damage . 0 ###LEFT-WALL### 2 helicases 0 ###LEFT-WALL### 33 . 1 xp 2 helicases 2 helicases 4 named 2 helicases 18 pigmentosum 2 helicases 23 are 3 , 4 named 4 named 5 for 4 named 12 - 5 for 7 role 6 their 7 role 7 role 8 in 8 in 11 sun 9 the 11 sun 10 extreme 11 sun 12 - 18 pigmentosum 13 mediated 14 skin 14 skin 18 pigmentosum 15 cancer 18 pigmentosum 16 predisposition 17 xeroderma 17 xeroderma 18 pigmentosum 18 pigmentosum 20 xp 18 pigmentosum 22 , 19 ( 20 xp 20 xp 21 ) 23 are 25 recruited 24 then 25 recruited 25 recruited 26 to 26 to 30 flanking 27 asymmetrically 30 flanking 30 flanking 32 damage 31 the 32 damage xpb and xpd genetic defects can also cause premature aging with profound neurological defects without increased cancers : cockayne [syndrome] ( cs ) and trichothiodystrophy ( ttd ) . 0 ###LEFT-WALL### 5 defects 0 ###LEFT-WALL### 8 cause 0 ###LEFT-WALL### 18 : 1 xpb 2 and 2 and 3 xpd 3 xpd 5 defects 4 genetic 5 defects 5 defects 6 can 6 can 8 cause 7 also 8 cause 8 cause 10 aging 8 cause 11 with 8 cause 15 without 9 premature 10 aging 11 with 14 defects 12 profound 14 defects 13 neurological 14 defects 15 without 17 cancers 16 increased 17 cancers 18 : 24 and 18 : 29 . 19 cockayne 22 cs 19 cockayne 24 and 21 ( 22 cs 22 cs 23 ) 24 and 25 trichothiodystrophy 24 and 27 ttd 26 ( 27 ttd 27 ttd 28 ) xp helicase [patient] phenotypes cannot be predicted from the mutation position along the linear gene sequence and adjacent mutations can cause different diseases . 0 ###LEFT-WALL### 1 xp 0 ###LEFT-WALL### 24 . 1 xp 2 helicase 1 xp 4 phenotypes 1 xp 5 cannot 2 helicase 4 phenotypes 5 cannot 17 and 6 be 7 predicted 6 be 17 and 7 predicted 8 from 7 predicted 12 along 8 from 11 position 9 the 11 position 10 mutation 11 position 12 along 16 sequence 13 the 16 sequence 14 linear 15 gene 15 gene 16 sequence 17 and 21 cause 18 adjacent 19 mutations 19 mutations 20 can 20 can 21 cause 21 cause 23 diseases 22 different 23 diseases here we consider the structural biology of dna damage recognition by xpc - rad23b , ddb1/ddb2 , rnapii , and atl , [and] of helix unwinding by the xpb and xpd helicases plus the bacterial repair helicases uvrb and uvrd in complex with dna . 0 ###LEFT-WALL### 2 we 0 ###LEFT-WALL### 3 consider 1 here 2 we 2 we 3 consider 3 consider 6 biology 3 consider 20 and 4 the 6 biology 5 structural 6 biology 6 biology 7 of 6 biology 16 ddb1/ddb2 7 of 10 recognition 8 dna 10 recognition 9 damage 10 recognition 10 recognition 11 by 11 by 12 xpc 12 xpc 14 rad23b 13 - 14 rad23b 14 rad23b 15 , 15 , 16 ddb1/ddb2 16 ddb1/ddb2 17 , 18 rnapii 20 and 19 , 20 and 20 and 21 atl 21 atl 24 of 22 , 24 of 24 of 30 and 24 of 45 . 25 helix 26 unwinding 25 helix 30 and 26 unwinding 27 by 27 by 29 xpb 28 the 29 xpb 30 and 31 xpd 30 and 32 helicases 30 and 42 complex 32 helicases 33 plus 32 helicases 36 repair 32 helicases 41 in 32 helicases 42 complex 33 plus 35 bacterial 34 the 35 bacterial 36 repair 37 helicases 37 helicases 40 uvrd 37 helicases 41 in 38 uvrb 39 and 39 and 40 uvrd 42 complex 43 with 43 with 44 dna we then propose unified models for tfiih [assembly] and roles in ner . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 3 propose 0 ###LEFT-WALL### 13 . 1 we 3 propose 2 then 3 propose 3 propose 5 models 3 propose 11 in 4 unified 5 models 5 models 6 for 6 for 9 and 7 tfiih 9 and 9 and 10 roles 11 in 12 ner collective crystal structures with nmr and electron microscopy results reveal functional motifs , domains , and architectural elements that contribute to biological activities : damaged dna binding , translocation , unwinding , and atp driven changes plus tfiih assembly and signaling . 0 ###LEFT-WALL### 6 and 0 ###LEFT-WALL### 24 : 1 collective 2 crystal 2 crystal 3 structures 3 structures 4 with 3 structures 6 and 4 with 5 nmr 6 and 8 microscopy 6 and 9 results 6 and 10 reveal 7 electron 8 microscopy 9 results 10 reveal 10 reveal 12 motifs 11 functional 12 motifs 12 motifs 16 and 13 , 16 and 14 domains 16 and 15 , 16 and 16 and 18 elements 16 and 19 that 16 and 20 contribute 16 and 24 : 17 architectural 18 elements 19 that 20 contribute 20 contribute 21 to 21 to 23 activities 22 biological 23 activities 24 : 40 and 24 : 42 . 25 damaged 26 dna 26 dna 27 binding 26 dna 28 , 28 , 29 translocation 28 , 30 , 30 , 39 assembly 30 , 40 and 31 unwinding 33 and 32 , 33 and 33 and 34 atp 33 and 37 plus 35 driven 36 changes 36 changes 37 plus 37 plus 39 assembly 38 tfiih 39 assembly 40 and 41 signaling coupled with mapping of patient mutations , these combined structural analyses provide a framework for integrating and unifying the rich biochemical and cellular information that has accumulated over forty years of study . 0 ###LEFT-WALL### 11 analyses 0 ###LEFT-WALL### 12 provide 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 33 . 1 coupled 2 with 1 coupled 7 , 1 coupled 11 analyses 2 with 3 mapping 3 mapping 4 of 4 of 6 mutations 5 patient 6 mutations 8 these 11 analyses 9 combined 11 analyses 10 structural 11 analyses 11 analyses 12 provide 12 provide 14 framework 12 provide 15 for 13 a 14 framework 15 for 16 integrating 17 and 18 unifying 17 and 27 accumulated 18 unifying 24 information 18 unifying 27 accumulated 19 the 24 information 20 rich 24 information 21 biochemical 22 and 22 and 23 cellular 22 and 24 information 24 information 25 that 24 information 26 has 25 that 26 has 27 accumulated 28 over 28 over 30 years 29 forty 30 years 30 years 31 of 31 of 32 study this integration resolves puzzles regarding xp helicase functions and suggests that xp helicase positions and activities within tfiih detect and [verify] damage , select the damaged strand [for] incision , and coordinate repair with transcription and cell cycle through cak signaling . 0 ###LEFT-WALL### 2 integration 0 ###LEFT-WALL### 3 resolves 0 ###LEFT-WALL### 23 , 0 ###LEFT-WALL### 42 . 1 this 2 integration 2 integration 3 resolves 3 resolves 20 and 4 puzzles 5 regarding 4 puzzles 20 and 5 regarding 6 xp 6 xp 7 helicase 6 xp 19 detect 7 helicase 9 and 8 functions 9 and 9 and 10 suggests 10 suggests 11 that 11 that 15 and 11 that 19 detect 12 xp 13 helicase 13 helicase 14 positions 14 positions 15 and 15 and 16 activities 15 and 17 within 17 within 18 tfiih 20 and 22 damage 20 and 23 , 23 , 24 select 23 , 31 and 24 select 29 incision 25 the 29 incision 26 damaged 29 incision 27 strand 29 incision 30 , 31 and 31 and 36 and 31 and 38 cycle 32 coordinate 33 repair 33 repair 34 with 33 repair 36 and 34 with 35 transcription 36 and 37 cell 36 and 38 cycle 38 cycle 39 through 39 through 40 cak 40 cak 41 signaling objective : to develop a high performance machine learning ( ml ) approach for predicting the age and consequently the state of brain development of infants , based on their event related potentials ( erps ) in response to an auditory stimulus . 0 ###LEFT-WALL### 1 objective 0 ###LEFT-WALL### 2 : 2 : 13 approach 2 : 43 . 3 to 4 develop 3 to 12 ) 3 to 13 approach 4 develop 8 machine 5 a 6 high 5 a 8 machine 6 high 7 performance 7 performance 8 machine 8 machine 9 learning 8 machine 11 ml 10 ( 11 ml 11 ml 12 ) 13 approach 14 for 13 approach 39 to 14 for 15 predicting 15 predicting 18 and 15 predicting 28 based 16 the 17 age 17 age 18 and 18 and 19 consequently 18 and 21 state 20 the 21 state 21 state 22 of 22 of 24 development 23 brain 24 development 24 development 25 of 25 of 26 infants 27 , 28 based 28 based 29 on 28 based 36 ) 29 on 33 potentials 30 their 33 potentials 31 event 32 related 32 related 33 potentials 33 potentials 35 erps 34 ( 35 erps 35 erps 36 ) 37 in 38 response 38 response 39 to 39 to 42 stimulus 40 an 42 stimulus 41 auditory 42 stimulus methods : the erp responses of twenty - nine [6] [-] month - olds , nineteen 12 - [month] - olds and 10 adults to an auditory stimulus were derived from electroencephalogram ( eeg ) recordings . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 30 derived 0 ###LEFT-WALL### 37 . 2 : 5 responses 2 : 13 - 3 the 5 responses 4 erp 5 responses 5 responses 6 of 6 of 12 month 7 twenty 8 - 8 - 9 nine 8 - 12 month 13 - 14 olds 13 - 15 , 13 - 18 - 15 , 16 nineteen 17 12 18 - 18 - 20 - 20 - 22 and 21 olds 22 and 22 and 24 adults 22 and 25 to 22 and 29 were 23 10 24 adults 25 to 28 stimulus 26 an 28 stimulus 27 auditory 28 stimulus 29 were 30 derived 30 derived 31 from 31 from 36 recordings 32 electroencephalogram 34 eeg 32 electroencephalogram 35 ) 32 electroencephalogram 36 recordings 33 ( 34 eeg 34 eeg 35 ) the most relevant wavelet coefficients corresponding to the first - and second - order moment sequences of the erp signals were then identified using a feature selection scheme that made no a priori assumptions about the features of interest . 0 ###LEFT-WALL### 3 relevant 0 ###LEFT-WALL### 4 wavelet 0 ###LEFT-WALL### 11 and 0 ###LEFT-WALL### 40 . 1 the 3 relevant 2 most 3 relevant 3 relevant 4 wavelet 4 wavelet 5 coefficients 5 coefficients 6 corresponding 5 coefficients 7 to 7 to 9 first 8 the 9 first 10 - 11 and 11 and 12 second 11 and 22 then 12 second 22 then 13 - 14 order 14 order 16 sequences 14 order 21 were 15 moment 16 sequences 16 sequences 17 of 17 of 20 signals 18 the 20 signals 19 erp 20 signals 21 were 22 then 22 then 23 identified 22 then 24 using 24 using 28 scheme 25 a 28 scheme 26 feature 27 selection 27 selection 28 scheme 28 scheme 29 that 28 scheme 30 made 28 scheme 38 of 29 that 30 made 30 made 34 assumptions 31 no 34 assumptions 32 a 33 priori 33 priori 34 assumptions 34 assumptions 35 about 35 about 37 features 36 the 37 features 38 of 39 interest these features [are] then fed into a classifier for determination of age group . 0 ###LEFT-WALL### 2 features 0 ###LEFT-WALL### 13 group 0 ###LEFT-WALL### 14 . 1 these 2 features 2 features 5 fed 2 features 13 group 4 then 5 fed 5 fed 6 into 6 into 8 classifier 7 a 8 classifier 8 classifier 9 for 9 for 10 determination 10 determination 11 of 11 of 12 age results : we verified that erp data could yield features that discriminate the age group of individual subjects with high reliability . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 3 we 2 : 4 verified 2 : 22 . 3 we 4 verified 4 verified 5 that 5 that 7 data 5 that 9 yield 6 erp 7 data 7 data 8 could 8 could 9 yield 9 yield 10 features 10 features 11 that 10 features 12 discriminate 11 that 12 discriminate 12 discriminate 15 group 12 discriminate 19 with 13 the 15 group 14 age 15 group 15 group 16 of 16 of 18 subjects 17 individual 18 subjects 19 with 21 reliability 20 high 21 reliability [a] low dimensional representation of the selected feature vectors show significant clustering behavior corresponding to the subject age group . 0 ###LEFT-WALL### 2 low 0 ###LEFT-WALL### 20 . 2 low 4 representation 2 low 15 to 3 dimensional 4 representation 4 representation 5 of 4 representation 14 corresponding 5 of 8 feature 6 the 8 feature 7 selected 8 feature 9 vectors 10 show 10 show 13 behavior 10 show 14 corresponding 11 significant 13 behavior 12 clustering 13 behavior 13 behavior 14 corresponding 15 to 19 group 16 the 19 group 17 subject 18 age 18 age 19 group the performance of the proposed age group prediction scheme was evaluated using the [leave] - one [-] out cross validation method and found to exceed 90 % accuracy . 0 ###LEFT-WALL### 2 performance 0 ###LEFT-WALL### 22 and 0 ###LEFT-WALL### 29 . 1 the 2 performance 2 performance 3 of 2 performance 22 and 3 of 9 scheme 4 the 9 scheme 5 proposed 9 scheme 6 age 9 scheme 7 group 8 prediction 8 prediction 9 scheme 10 was 11 evaluated 10 was 22 and 11 evaluated 12 using 12 using 21 method 13 the 16 one 15 - 16 one 16 one 21 method 18 out 19 cross 19 cross 21 method 20 validation 21 method 22 and 23 found 22 and 24 to 22 and 28 accuracy 24 to 25 exceed 25 exceed 27 % 26 90 27 % conclusions : this study indicates that erp responses to an acoustic stimulus can be used to predict the age and consequently the state of brain development of infants . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 2 : 2 : 4 study 2 : 5 indicates 2 : 29 . 3 this 4 study 4 study 5 indicates 5 indicates 6 that 6 that 8 responses 6 that 15 used 7 erp 8 responses 8 responses 9 to 8 responses 13 can 9 to 12 stimulus 10 an 12 stimulus 11 acoustic 12 stimulus 13 can 14 be 14 be 15 used 15 used 16 to 16 to 17 predict 17 predict 20 and 18 the 19 age 19 age 20 and 20 and 21 consequently 20 and 23 state 22 the 23 state 23 state 24 of 23 state 27 of 24 of 26 development 25 brain 26 development 27 of 28 infants significance : this study is of fundamental scientific significance in demonstrating that a machine classification algorithm with no a priori assumptions can classify erp responses according to age and with further work , potentially provide useful clues in the understanding of the development of the human brain . 0 ###LEFT-WALL### 1 significance 0 ###LEFT-WALL### 2 : 2 : 4 study 2 : 5 is 2 : 48 . 3 this 4 study 4 study 5 is 5 is 6 of 5 is 10 in 5 is 38 in 6 of 9 significance 7 fundamental 9 significance 8 scientific 9 significance 10 in 11 demonstrating 11 demonstrating 12 that 12 that 16 algorithm 12 that 33 , 13 a 16 algorithm 14 machine 15 classification 15 classification 16 algorithm 16 algorithm 17 with 16 algorithm 22 can 17 with 21 assumptions 18 no 21 assumptions 19 a 20 priori 20 priori 21 assumptions 22 can 33 , 23 classify 26 according 23 classify 29 and 23 classify 33 , 24 erp 26 according 25 responses 26 according 27 to 28 age 27 to 29 and 29 and 30 with 30 with 32 work 31 further 32 work 33 , 35 provide 34 potentially 35 provide 35 provide 37 clues 36 useful 37 clues 38 in 40 understanding 39 the 40 understanding 40 understanding 41 of 41 of 43 development 42 the 43 development 43 development 44 of 44 of 47 brain 45 the 47 brain 46 human 47 brain a potential clinical use for the proposed methodology is the identification of developmental delay : an abnormal condition may be suspected if the age estimated by the proposed technique is significantly less than the chronological age of the subject . 0 ###LEFT-WALL### 4 use 0 ###LEFT-WALL### 9 is 0 ###LEFT-WALL### 15 : 1 a 4 use 2 potential 4 use 3 clinical 4 use 4 use 5 for 4 use 9 is 5 for 8 methodology 6 the 8 methodology 7 proposed 8 methodology 9 is 11 identification 10 the 11 identification 11 identification 12 of 12 of 14 delay 13 developmental 14 delay 15 : 18 condition 15 : 21 suspected 15 : 40 . 16 an 17 abnormal 16 an 18 condition 17 abnormal 18 condition 18 condition 19 may 19 may 20 be 20 be 21 suspected 21 suspected 22 if 22 if 24 age 22 if 30 is 23 the 24 age 24 age 25 estimated 24 age 30 is 25 estimated 26 by 26 by 29 technique 27 the 29 technique 28 proposed 29 technique 30 is 32 less 30 is 33 than 31 significantly 32 less 33 than 36 age 34 the 36 age 35 chronological 36 age 36 age 37 of 37 of 39 subject 38 the 39 subject dendritic cells ( dcs ) are central in regulating both innate and acquired immunity , but their possible age - related functional modifications are still unclear . 0 ###LEFT-WALL### 1 dendritic 0 ###LEFT-WALL### 6 are 0 ###LEFT-WALL### 20 - 1 dendritic 6 are 2 cells 4 dcs 2 cells 6 are 3 ( 4 dcs 4 dcs 5 ) 6 are 7 central 7 central 8 in 8 in 9 regulating 9 regulating 12 and 10 both 12 and 11 innate 12 and 12 and 14 immunity 12 and 16 but 13 acquired 14 immunity 15 , 16 but 16 but 19 age 16 but 20 - 17 their 19 age 18 possible 19 age 20 - 23 modifications 20 - 24 are 20 - 27 . 21 related 23 modifications 22 functional 23 modifications 23 modifications 24 are 24 are 25 still 24 are 26 unclear 25 still 26 unclear here we have analyzed the effect of age on lps - treated monocyte - derived dcs ( mddcs ) . 0 ###LEFT-WALL### 2 we 0 ###LEFT-WALL### 4 analyzed 0 ###LEFT-WALL### 20 . 1 here 2 we 2 we 3 have 3 have 4 analyzed 4 analyzed 6 effect 4 analyzed 15 derived 5 the 6 effect 6 effect 7 of 6 effect 15 derived 7 of 8 age 8 age 9 on 9 on 10 lps 10 lps 13 monocyte 11 - 13 monocyte 12 treated 13 monocyte 13 monocyte 14 - 15 derived 16 dcs 16 dcs 18 mddcs 17 ( 18 mddcs 18 mddcs 19 ) a negative correlation between age and cell expression of icam - 1 , cd25 and il - [10] was observed in a group of healthy donors . 0 ###LEFT-WALL### 3 correlation 0 ###LEFT-WALL### 20 observed 0 ###LEFT-WALL### 27 . 1 a 3 correlation 2 negative 3 correlation 3 correlation 4 between 3 correlation 16 il 3 correlation 19 was 4 between 6 and 5 age 6 and 6 and 8 expression 7 cell 8 expression 8 expression 9 of 9 of 10 icam 10 icam 12 1 11 - 12 1 12 1 13 , 13 , 16 il 14 cd25 15 and 15 and 16 il 16 il 17 - 19 was 20 observed 20 observed 21 in 21 in 26 donors 22 a 23 group 23 group 24 of 23 group 26 donors 24 of 26 donors 25 healthy 26 donors this has been confirmed by a significantly reduced expression of the same molecules in cells [of] subgrouped elderly versus younger individuals . 0 ###LEFT-WALL### 1 this 0 ###LEFT-WALL### 4 confirmed 0 ###LEFT-WALL### 22 . 1 this 2 has 2 has 3 been 3 been 4 confirmed 4 confirmed 5 by 4 confirmed 14 in 5 by 9 expression 6 a 9 expression 7 significantly 8 reduced 8 reduced 9 expression 9 expression 10 of 10 of 13 molecules 11 the 12 same 12 same 13 molecules 14 in 15 cells 15 cells 17 subgrouped 15 cells 19 versus 17 subgrouped 18 elderly 19 versus 21 individuals 20 younger 21 individuals on the contrary , a positive correlation between age and cell expression of il - 6 and [il] - 18 has been reported in all the subjects and further supported by a significant increase of the two pro - inflammatory cytokines in cells of elderly [versus] young subjects . 0 ###LEFT-WALL### 7 correlation 0 ###LEFT-WALL### 28 and 0 ###LEFT-WALL### 39 - 0 ###LEFT-WALL### 49 . 1 on 3 contrary 1 on 4 , 1 on 7 correlation 2 the 3 contrary 5 a 6 positive 5 a 7 correlation 6 positive 7 correlation 7 correlation 8 between 7 correlation 21 has 8 between 10 and 9 age 10 and 10 and 12 expression 10 and 13 of 11 cell 12 expression 13 of 14 il 14 il 17 and 15 - 16 6 16 6 17 and 17 and 20 18 19 - 20 18 21 has 22 been 22 been 28 and 23 reported 24 in 23 reported 28 and 24 in 25 all 25 all 26 the 25 all 27 subjects 26 the 27 subjects 28 and 30 supported 28 and 31 by 29 further 30 supported 31 by 34 increase 32 a 33 significant 32 a 34 increase 33 significant 34 increase 34 increase 35 of 35 of 38 pro 36 the 38 pro 37 two 38 pro 39 - 41 cytokines 40 inflammatory 41 cytokines 41 cytokines 42 in 41 cytokines 44 of 42 in 43 cells 44 of 48 subjects 45 elderly 48 subjects 47 young 48 subjects our data indicate that aging can impair the expression of icam [-] 1 and cd25 and skew the production of cytokines , including il - 18 , which concur to make a pro - inflammatory milieu . 0 ###LEFT-WALL### 2 data 0 ###LEFT-WALL### 16 and 0 ###LEFT-WALL### 25 - 0 ###LEFT-WALL### 37 . 1 our 2 data 2 data 16 and 3 indicate 4 that 3 indicate 16 and 4 that 5 aging 4 that 7 impair 5 aging 6 can 6 can 7 impair 7 impair 9 expression 8 the 9 expression 9 expression 10 of 10 of 14 and 11 icam 13 1 11 icam 14 and 14 and 15 cd25 16 and 17 skew 16 and 19 production 18 the 19 production 19 production 20 of 19 production 23 including 20 of 21 cytokines 22 , 23 including 23 including 24 il 23 including 25 - 25 - 26 18 25 - 27 , 25 - 34 - 27 , 28 which 27 , 29 concur 28 which 29 concur 29 concur 30 to 30 to 31 make 31 make 33 pro 32 a 33 pro 34 - 36 milieu 35 inflammatory 36 milieu altogether , the present results point to additional molecules whose role might be relevant in immunosenescence of human dcs , confirming that these cells undergo functional changes during aging . 0 ###LEFT-WALL### 5 results 0 ###LEFT-WALL### 6 point 1 altogether 2 , 1 altogether 5 results 3 the 5 results 4 present 5 results 5 results 6 point 6 point 7 to 7 to 9 molecules 8 additional 9 molecules 9 molecules 10 whose 9 molecules 17 of 10 whose 11 role 11 role 12 might 12 might 13 be 13 be 14 relevant 14 relevant 15 in 15 in 16 immunosenescence 17 of 19 dcs 18 human 19 dcs 19 dcs 21 confirming 20 , 21 confirming 21 confirming 22 that 21 confirming 30 . 22 that 24 cells 22 that 25 undergo 23 these 24 cells 24 cells 25 undergo 25 undergo 27 changes 25 undergo 28 during 26 functional 27 changes 28 during 29 aging transcranial magnetic stimulation ( tms ) is a neuropsychiatric tool that can serve as a useful method to better understand the neurobiology [of] cognitive function , behavior , and emotional processing . 0 ###LEFT-WALL### 3 stimulation 0 ###LEFT-WALL### 7 is 0 ###LEFT-WALL### 26 , 0 ###LEFT-WALL### 32 . 1 transcranial 3 stimulation 2 magnetic 3 stimulation 3 stimulation 5 tms 3 stimulation 7 is 4 ( 5 tms 5 tms 6 ) 7 is 10 tool 7 is 14 as 7 is 18 to 8 a 10 tool 9 neuropsychiatric 10 tool 10 tool 11 that 10 tool 12 can 11 that 12 can 12 can 13 serve 14 as 17 method 15 a 17 method 16 useful 17 method 18 to 20 understand 19 better 20 understand 20 understand 25 function 21 the 25 function 22 neurobiology 25 function 24 cognitive 25 function 26 , 29 and 27 behavior 29 and 28 , 29 and 29 and 31 processing 30 emotional 31 processing the purpose of this article is to examine the utility of tms as a means to measure neocortical [function] in neuropsychiatric disorders in general , and schizophrenia in particular , for the cognitive neuroscience treatment research to improve cognition in schizophrenia initiative . 0 ###LEFT-WALL### 2 purpose 0 ###LEFT-WALL### 6 is 0 ###LEFT-WALL### 43 . 1 the 2 purpose 2 purpose 3 of 2 purpose 6 is 3 of 5 article 4 this 5 article 6 is 7 to 6 is 18 neocortical 7 to 8 examine 8 examine 10 utility 8 examine 13 as 9 the 10 utility 10 utility 11 of 11 of 12 tms 13 as 15 means 14 a 15 means 15 means 16 to 15 means 17 measure 16 to 17 measure 18 neocortical 20 in 20 in 26 and 21 neuropsychiatric 22 disorders 22 disorders 24 general 22 disorders 26 and 23 in 24 general 25 , 26 and 26 and 27 schizophrenia 26 and 30 , 26 and 31 for 26 and 37 to 26 and 40 in 27 schizophrenia 29 particular 28 in 29 particular 31 for 36 research 32 the 36 research 33 cognitive 34 neuroscience 34 neuroscience 35 treatment 35 treatment 36 research 37 to 39 cognition 38 improve 39 cognition 40 in 42 initiative 41 schizophrenia 42 initiative when incorporating tms paradigms in research studies , methodologic considerations include technical aspects of tms , cohort selection and confounding factors , and subject safety . 0 ###LEFT-WALL### 10 considerations 0 ###LEFT-WALL### 23 and 0 ###LEFT-WALL### 26 . 1 when 2 incorporating 1 when 8 , 1 when 10 considerations 2 incorporating 4 paradigms 3 tms 4 paradigms 4 paradigms 5 in 5 in 7 studies 6 research 7 studies 9 methodologic 10 considerations 10 considerations 23 and 11 include 13 aspects 11 include 23 and 12 technical 13 aspects 13 aspects 14 of 13 aspects 19 and 14 of 15 tms 16 , 19 and 17 cohort 18 selection 18 selection 19 and 19 and 21 factors 19 and 22 , 20 confounding 21 factors 22 , 23 and 23 and 24 subject 24 subject 25 safety with the multiple tms techniques including single - pulse , paired - pulse , paired associative stimulation , and repetitive tms and theta burst stimulation , combined with neurophysiologic and neuroimaging methods , there exists a plethora of tms experimental paradigms to modulate neocortical physiologic processes . 0 ###LEFT-WALL### 13 pulse 0 ###LEFT-WALL### 14 , 0 ###LEFT-WALL### 47 . 1 with 9 pulse 1 with 12 - 1 with 13 pulse 2 the 9 pulse 3 multiple 5 techniques 4 tms 5 techniques 5 techniques 9 pulse 6 including 9 pulse 7 single 8 - 7 single 9 pulse 9 pulse 11 paired 10 , 11 paired 11 paired 12 - 14 , 22 and 14 , 24 burst 14 , 33 , 15 paired 17 stimulation 16 associative 17 stimulation 17 stimulation 19 and 18 , 19 and 19 and 21 tms 19 and 22 and 20 repetitive 21 tms 22 and 23 theta 22 and 24 burst 24 burst 25 stimulation 25 stimulation 27 combined 26 , 27 combined 27 combined 28 with 27 combined 33 , 28 with 30 and 29 neurophysiologic 30 and 30 and 32 methods 31 neuroimaging 32 methods 33 , 34 there 33 , 35 exists 34 there 35 exists 35 exists 37 plethora 36 a 37 plethora 37 plethora 38 of 38 of 41 paradigms 39 tms 41 paradigms 40 experimental 41 paradigms 41 paradigms 42 to 41 paradigms 43 modulate 42 to 43 modulate 43 modulate 46 processes 44 neocortical 46 processes 45 physiologic 46 processes specifically , tms can measure cortical excitability , intracortical inhibitory and excitatory mechanisms , and local and network cortical plasticity . 0 ###LEFT-WALL### 3 tms 0 ###LEFT-WALL### 17 and 0 ###LEFT-WALL### 21 . 1 specifically 2 , 1 specifically 3 tms 3 tms 4 can 4 can 17 and 5 measure 15 and 5 measure 17 and 6 cortical 7 excitability 7 excitability 8 , 8 , 13 mechanisms 8 , 15 and 9 intracortical 13 mechanisms 10 inhibitory 11 and 11 and 12 excitatory 11 and 13 mechanisms 14 , 15 and 15 and 16 local 17 and 18 network 17 and 20 plasticity 19 cortical 20 plasticity coupled with functional and electrophysiologic modalities , tms can provide insight into the mechanisms underlying healthy neurodevelopment and aging , as well as neuropsychiatric pathology . 0 ###LEFT-WALL### 8 tms 0 ###LEFT-WALL### 10 provide 0 ###LEFT-WALL### 26 . 1 coupled 2 with 1 coupled 7 , 1 coupled 8 tms 2 with 6 modalities 3 functional 4 and 4 and 5 electrophysiologic 4 and 6 modalities 8 tms 9 can 9 can 10 provide 10 provide 11 insight 10 provide 12 into 10 provide 21 as 12 into 18 and 13 the 14 mechanisms 14 mechanisms 15 underlying 14 mechanisms 18 and 15 underlying 17 neurodevelopment 16 healthy 17 neurodevelopment 18 and 19 aging 18 and 20 , 21 as 25 pathology 22 well 25 pathology 23 as 24 neuropsychiatric 24 neuropsychiatric 25 pathology thus , tms could be a useful tool in the cognitive neuroscience treatment research to improve cognition in schizophrenia armamentarium of biomarker methods . 0 ###LEFT-WALL### 3 tms 0 ###LEFT-WALL### 5 be 0 ###LEFT-WALL### 24 . 1 thus 2 , 1 thus 3 tms 3 tms 4 could 4 could 5 be 5 be 8 tool 5 be 9 in 5 be 15 to 5 be 18 in 6 a 8 tool 7 useful 8 tool 9 in 14 research 10 the 14 research 11 cognitive 12 neuroscience 12 neuroscience 13 treatment 13 treatment 14 research 15 to 17 cognition 16 improve 17 cognition 18 in 20 armamentarium 19 schizophrenia 20 armamentarium 20 armamentarium 21 of 21 of 23 methods 22 biomarker 23 methods future investigations are warranted to optimize tms methodologies for this purpose . 0 ###LEFT-WALL### 2 investigations 0 ###LEFT-WALL### 4 warranted 0 ###LEFT-WALL### 12 . 1 future 2 investigations 2 investigations 3 are 3 are 4 warranted 4 warranted 5 to 5 to 6 optimize 6 optimize 8 methodologies 7 tms 8 methodologies 8 methodologies 9 for 9 for 11 purpose 10 this 11 purpose the prognostic significance , interdependence , and hierarchy of cardiovascular risk factors could evolve with advancing age . 0 ###LEFT-WALL### 7 and 0 ###LEFT-WALL### 18 . 1 the 3 significance 2 prognostic 3 significance 3 significance 4 , 4 , 5 interdependence 4 , 7 and 6 , 7 and 7 and 8 hierarchy 7 and 9 of 9 of 11 risk 10 cardiovascular 11 risk 11 risk 12 factors 11 risk 14 evolve 12 factors 13 could 13 could 14 evolve 14 evolve 15 with 15 with 16 advancing 16 advancing 17 age our study reports on the interdependence among blood pressure ( bp ) , other metabolic syndrome components , and high - sensitivity c - reactive protein according to age in hypertensive subjects . 0 ###LEFT-WALL### 2 study 0 ###LEFT-WALL### 3 reports 0 ###LEFT-WALL### 33 . 1 our 2 study 2 study 3 reports 3 reports 4 on 3 reports 28 to 4 on 19 and 5 the 6 interdependence 6 interdependence 7 among 6 interdependence 13 , 7 among 9 pressure 8 blood 9 pressure 9 pressure 11 bp 10 ( 11 bp 11 bp 12 ) 13 , 17 components 13 , 19 and 14 other 17 components 15 metabolic 16 syndrome 16 syndrome 17 components 18 , 19 and 19 and 26 protein 20 high 22 sensitivity 20 high 26 protein 21 - 22 sensitivity 22 sensitivity 23 c 22 sensitivity 24 - 25 reactive 26 protein 27 according 28 to 28 to 29 age 29 age 30 in 30 in 32 subjects 31 hypertensive 32 subjects a total of 5,712 nondiabetic patients ( 50.1 % men , age range 40 to 95 years ) evaluated in outpatient hypertension clinics were included and divided into 5 age groups ( age 40 to 49 , 50 to 59 , 60 to 69 , 70 to 79 , and >80 years ) . 0 ###LEFT-WALL### 50 and 0 ###LEFT-WALL### 54 . 1 a 2 total 2 total 3 of 2 total 50 and 3 of 4 5,712 4 5,712 6 patients 4 5,712 19 evaluated 4 5,712 20 in 5 nondiabetic 6 patients 6 patients 10 men 6 patients 19 evaluated 7 ( 10 men 8 50.1 9 % 9 % 10 men 10 men 17 years 10 men 18 ) 11 , 17 years 12 age 17 years 13 range 15 to 13 range 17 years 14 40 15 to 15 to 16 95 17 years 18 ) 20 in 23 clinics 21 outpatient 23 clinics 22 hypertension 23 clinics 23 clinics 26 and 23 clinics 28 into 23 clinics 33 age 23 clinics 38 50 24 were 25 included 24 were 26 and 26 and 27 divided 28 into 31 groups 29 5 31 groups 30 age 31 groups 32 ( 33 age 33 age 35 to 33 age 37 , 34 40 35 to 35 to 36 49 37 , 38 50 38 50 39 to 38 50 43 to 38 50 49 , 39 to 40 59 41 , 43 to 42 60 43 to 43 to 44 69 43 to 47 to 43 to 49 , 45 , 47 to 46 70 47 to 47 to 48 79 47 to 49 , 50 and 52 years 50 and 53 ) 51 >80 52 years bp , evaluated by [both] office [and] 24 - hour ambulatory bp monitoring , and the metabolic and inflammation parameters were determined after a ≥2 - week drug washout period . 0 ###LEFT-WALL### 20 parameters 0 ###LEFT-WALL### 22 determined 0 ###LEFT-WALL### 31 . 1 bp 2 , 1 bp 20 parameters 2 , 3 evaluated 3 evaluated 4 by 3 evaluated 9 - 3 evaluated 20 parameters 4 by 6 office 6 office 8 24 10 hour 20 parameters 11 ambulatory 13 monitoring 12 bp 13 monitoring 13 monitoring 15 and 14 , 15 and 15 and 17 metabolic 15 and 18 and 16 the 17 metabolic 18 and 19 inflammation 18 and 20 parameters 20 parameters 21 were 21 were 22 determined 22 determined 23 after 23 after 30 period 24 a 30 period 25 ≥2 26 - 25 ≥2 30 period 27 week 30 period 28 drug 30 period 29 washout 30 period the prevalence of the metabolic syndrome ( adult treatment panel iii definition ) remained stable across the age groups . 0 ###LEFT-WALL### 2 prevalence 0 ###LEFT-WALL### 14 remained 0 ###LEFT-WALL### 20 . 1 the 2 prevalence 2 prevalence 3 of 2 prevalence 14 remained 3 of 6 syndrome 4 the 6 syndrome 5 metabolic 6 syndrome 6 syndrome 12 definition 7 ( 12 definition 8 adult 12 definition 9 treatment 10 panel 10 panel 11 iii 10 panel 12 definition 12 definition 13 ) 14 remained 15 stable 15 stable 16 across 16 across 19 groups 17 the 19 groups 18 age 19 groups we observed a stable or increased association [between] waist circumference and insulin resistance ( homeostasis model of assessment - insulin resistance [index] ) and fasting plasma glucose . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 observed 0 ###LEFT-WALL### 28 . 1 we 2 observed 2 observed 24 and 3 a 4 stable 4 stable 5 or 5 or 10 circumference 5 or 11 and 6 increased 7 association 7 association 10 circumference 9 waist 10 circumference 11 and 13 resistance 11 and 16 model 11 and 24 and 12 insulin 13 resistance 14 ( 16 model 15 homeostasis 16 model 16 model 17 of 16 model 23 ) 17 of 18 assessment 18 assessment 21 resistance 19 - 21 resistance 20 insulin 21 resistance 21 resistance 23 ) 24 and 27 glucose 25 fasting 26 plasma 26 plasma 27 glucose however , the association between waist circumference and ambulatory bp monitoring systolic bp ( [r] [(] 2 ) decrease from 9.9 % to 1.0 % , p < 0.001 ) , high - density lipoprotein cholesterol ( [r] [(] 2 ) decreased from 21 % to 4.9 % , p = 0.002 [ )( [and] triglyceride levels ( [r] [(] 2 ) decreased from 17.5 % to 1.9 % , p < 0.001 ) decreased [with] age . 1 however 2 , 1 however 8 and 3 the 4 association 4 association 5 between 4 association 8 and 5 between 7 circumference 6 waist 7 circumference 8 and 10 bp 8 and 17 2 8 and 19 decrease 9 ambulatory 10 bp 10 bp 11 monitoring 11 monitoring 13 bp 12 systolic 13 bp 14 ( 17 2 17 2 18 ) 19 decrease 20 from 19 decrease 23 to 20 from 22 % 21 9.9 22 % 23 to 25 % 24 1.0 25 % 25 % 28 < 25 % 33 - 26 , 28 < 27 p 28 < 28 < 29 0.001 28 < 30 ) 31 , 33 - 32 high 33 - 33 - 35 lipoprotein 34 density 35 lipoprotein 35 lipoprotein 36 cholesterol 35 lipoprotein 42 decreased 35 lipoprotein 46 to 36 cholesterol 40 2 36 cholesterol 42 decreased 37 ( 40 2 40 2 41 ) 42 decreased 43 from 43 from 45 % 44 21 45 % 46 to 48 % 47 4.9 48 % 48 % 51 = 49 , 51 = 50 p 51 = 51 = 52 0.002 52 0.002 57 levels 52 0.002 63 decreased 56 triglyceride 57 levels 57 levels 61 2 57 levels 63 decreased 58 ( 61 2 61 2 62 ) 63 decreased 64 from 64 from 67 to 65 17.5 66 % 65 17.5 67 to 67 to 68 1.9 68 1.9 69 % 69 % 72 < 69 % 75 decreased 70 , 72 < 71 p 72 < 72 < 73 0.001 72 < 74 ) 75 decreased 77 age 75 decreased 78 . high - sensitivity c - reactive protein correlated with all metabolic syndrome components in all age groups ( p < 0.001 for all ) . 0 ###LEFT-WALL### 1 high 0 ###LEFT-WALL### 2 - 0 ###LEFT-WALL### 25 . 2 - 3 sensitivity 3 sensitivity 4 c 3 sensitivity 7 protein 5 - 7 protein 6 reactive 7 protein 7 protein 8 correlated 7 protein 24 ) 8 correlated 9 with 8 correlated 22 for 9 with 13 components 10 all 13 components 11 metabolic 12 syndrome 12 syndrome 13 components 13 components 14 in 13 components 20 < 14 in 17 groups 15 all 17 groups 16 age 17 groups 18 ( 20 < 19 p 20 < 20 < 21 0.001 22 for 23 all it became the strongest determinant of ambulatory bp monitoring systolic bp ( p < 0.001 ) and high - density lipoprotein cholesterol ( p < 0.05 ) in patients >80 years old . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 2 became 0 ###LEFT-WALL### 33 . 1 it 2 became 2 became 17 and 2 became 28 in 3 the 4 strongest 3 the 5 determinant 5 determinant 6 of 5 determinant 9 monitoring 5 determinant 17 and 6 of 8 bp 7 ambulatory 8 bp 9 monitoring 11 bp 10 systolic 11 bp 11 bp 14 < 12 ( 14 < 13 p 14 < 14 < 15 0.001 14 < 16 ) 17 and 22 cholesterol 17 and 25 < 18 high 19 - 18 high 20 density 20 density 22 cholesterol 21 lipoprotein 22 cholesterol 23 ( 25 < 24 p 25 < 25 < 26 0.05 25 < 27 ) 28 in 30 >80 29 patients 30 >80 30 >80 32 old 31 years 32 old in contrast , its association [with] waist circumference markedly decreased . 0 ###LEFT-WALL### 8 circumference 0 ###LEFT-WALL### 10 decreased 0 ###LEFT-WALL### 11 . 1 in 2 contrast 1 in 3 , 1 in 8 circumference 4 its 8 circumference 5 association 8 circumference 7 waist 8 circumference 8 circumference 10 decreased 9 markedly 10 decreased in conclusion , hypertension and dyslipidemia , but not fasting plasma glucose , dissociate from central obesity with advancing age . 0 ###LEFT-WALL### 14 dissociate 0 ###LEFT-WALL### 21 . 1 in 5 and 1 in 14 dissociate 2 conclusion 3 , 3 , 4 hypertension 3 , 5 and 5 and 6 dyslipidemia 5 and 8 but 7 , 8 but 8 but 9 not 8 but 12 glucose 8 but 13 , 9 not 10 fasting 11 plasma 12 glucose 14 dissociate 15 from 14 dissociate 18 with 14 dissociate 20 age 15 from 17 obesity 16 central 17 obesity 18 with 19 advancing they are increasingly determined by low - grade inflammation , independently of central obesity . 0 ###LEFT-WALL### 1 they 0 ###LEFT-WALL### 2 are 1 they 2 are 2 are 3 increasingly 2 are 4 determined 4 determined 5 by 4 determined 11 independently 5 by 9 inflammation 6 low 7 - 6 low 8 grade 8 grade 9 inflammation 10 , 11 independently 11 independently 12 of 11 independently 15 . 12 of 14 obesity 13 central 14 obesity these changing associations might underlie the weakening of obesity as a cardiovascular risk factor in older persons . 0 ###LEFT-WALL### 3 associations 0 ###LEFT-WALL### 5 underlie 0 ###LEFT-WALL### 18 . 1 these 3 associations 2 changing 3 associations 3 associations 4 might 4 might 5 underlie 5 underlie 7 weakening 5 underlie 10 as 5 underlie 15 in 6 the 7 weakening 7 weakening 8 of 8 of 9 obesity 10 as 14 factor 11 a 12 cardiovascular 11 a 14 factor 12 cardiovascular 14 factor 13 risk 14 factor 15 in 17 persons 16 older 17 persons skin aging has received tremendous attention in recent years by both scientists and the lay public . 0 ###LEFT-WALL### 1 skin 0 ###LEFT-WALL### 4 received 0 ###LEFT-WALL### 17 . 1 skin 2 aging 1 skin 3 has 3 has 4 received 4 received 6 attention 4 received 7 in 4 received 10 by 5 tremendous 6 attention 7 in 9 years 8 recent 9 years 10 by 13 and 11 both 13 and 12 scientists 13 and 13 and 16 public 14 the 16 public 15 lay 16 public this article reviews the evidence that homocysteine , an intermediary sulfhydryl - containing amino acid implicated in atherosclerosis , can accelerate skin aging and the aging of internal organs ( [universal] aging ) . 0 ###LEFT-WALL### 2 article 0 ###LEFT-WALL### 3 reviews 0 ###LEFT-WALL### 34 . 1 this 2 article 2 article 3 reviews 3 reviews 5 evidence 4 the 5 evidence 5 evidence 6 that 6 that 7 homocysteine 6 that 21 accelerate 7 homocysteine 11 sulfhydryl 7 homocysteine 13 containing 7 homocysteine 20 can 8 , 11 sulfhydryl 9 an 11 sulfhydryl 10 intermediary 11 sulfhydryl 11 sulfhydryl 12 - 12 - 13 containing 13 containing 15 acid 13 containing 19 , 14 amino 15 acid 15 acid 16 implicated 15 acid 17 in 17 in 18 atherosclerosis 20 can 21 accelerate 21 accelerate 24 and 22 skin 23 aging 22 skin 24 and 24 and 26 aging 24 and 27 of 24 and 32 aging 25 the 26 aging 27 of 29 organs 28 internal 29 organs 30 ( 32 aging 32 aging 33 ) background : vague and inexact word usage can complicate conversations about cutaneous energy devices , especially novel technologies . 0 ###LEFT-WALL### 1 background 0 ###LEFT-WALL### 2 : 2 : 4 and 2 : 9 complicate 2 : 15 , 2 : 19 . 3 vague 4 and 4 and 8 can 4 and 9 complicate 5 inexact 6 word 6 word 8 can 7 usage 8 can 9 complicate 10 conversations 9 complicate 11 about 11 about 14 devices 12 cutaneous 13 energy 13 energy 14 devices 15 , 18 technologies 16 especially 17 novel 17 novel 18 technologies objective : to identify some areas in which descriptions of lasers , lights , and energy devices can be improved . 1 objective 2 : 2 : 3 to 2 : 4 identify 3 to 4 identify 4 identify 6 areas 5 some 6 areas 6 areas 7 in 7 in 8 which 7 in 15 and 7 in 20 improved 9 descriptions 10 of 9 descriptions 15 and 10 of 11 lasers 11 lasers 13 lights 12 , 13 lights 13 lights 14 , 15 and 17 devices 15 and 18 can 16 energy 17 devices 18 can 19 be 19 be 20 improved 20 improved 21 . methods : ambiguities in descriptions of energy devices are addressed by suggesting sets of modifiers that are precise , accurate , simple , and mutually exclusive . 0 ###LEFT-WALL### 1 methods 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 27 . 1 methods 2 : 2 : 3 ambiguities 3 ambiguities 4 in 3 ambiguities 12 suggesting 4 in 5 descriptions 5 descriptions 6 of 6 of 7 energy 7 energy 8 devices 7 energy 11 by 8 devices 9 are 9 are 10 addressed 10 addressed 11 by 12 suggesting 13 sets 13 sets 14 of 13 sets 16 that 13 sets 17 are 14 of 15 modifiers 16 that 17 are 17 are 24 and 18 precise 19 , 19 , 20 accurate 19 , 21 , 21 , 22 simple 21 , 24 and 23 , 24 and 24 and 26 exclusive 25 mutually 26 exclusive results : terms are proposed for distinguishing between devices that induce skin injuries of different depths . 0 ###LEFT-WALL### 1 results 0 ###LEFT-WALL### 2 : 2 : 3 terms 2 : 5 proposed 2 : 17 . 3 terms 4 are 4 are 5 proposed 5 proposed 6 for 6 for 7 distinguishing 7 distinguishing 8 between 8 between 9 devices 9 devices 10 that 9 devices 11 induce 10 that 11 induce 11 induce 13 injuries 12 skin 13 injuries 13 injuries 14 of 14 of 16 depths 15 different 16 depths additionally , descriptors are suggested for fractional treatments , fat melting , and cellulite reduction . 0 ###LEFT-WALL### 3 descriptors 0 ###LEFT-WALL### 5 suggested 0 ###LEFT-WALL### 16 . 1 additionally 2 , 1 additionally 3 descriptors 3 descriptors 4 are 4 are 5 suggested 5 suggested 6 for 6 for 13 and 7 fractional 8 treatments 8 treatments 9 , 9 , 10 fat 9 , 13 and 10 fat 11 melting 12 , 13 and 13 and 15 reduction 14 cellulite 15 reduction finally , we propose a scheme for clearly naming the underlying technology associated with any cutaneous energy device . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 4 propose 0 ###LEFT-WALL### 19 . 1 finally 2 , 1 finally 3 we 3 we 4 propose 4 propose 6 scheme 5 a 6 scheme 6 scheme 7 for 7 for 9 naming 8 clearly 9 naming 9 naming 11 underlying 9 naming 12 technology 10 the 11 underlying 12 technology 13 associated 13 associated 14 with 14 with 18 device 15 any 18 device 16 cutaneous 17 energy 17 energy 18 device limitations : novel devices yet to be invented may not fit into the designations proposed and may require additional categories . 0 ###LEFT-WALL### 1 limitations 0 ###LEFT-WALL### 2 : 0 ###LEFT-WALL### 21 . 1 limitations 2 : 2 : 4 devices 3 novel 4 devices 4 devices 6 to 4 devices 7 be 4 devices 8 invented 4 devices 16 and 5 yet 6 to 6 to 7 be 9 may 10 not 9 may 11 fit 9 may 16 and 11 fit 12 into 12 into 14 designations 13 the 14 designations 14 designations 15 proposed 16 and 17 may 17 may 18 require 18 require 20 categories 19 additional 20 categories conclusions : simple changes in word usage may facilitate rapid and accurate communication regarding lasers , lights , and other energy devices . 0 ###LEFT-WALL### 1 conclusions 0 ###LEFT-WALL### 9 facilitate 0 ###LEFT-WALL### 23 . 1 conclusions 2 : 2 : 3 simple 3 simple 4 changes 3 simple 9 facilitate 4 changes 5 in 4 changes 8 may 5 in 7 usage 6 word 7 usage 8 may 9 facilitate 9 facilitate 13 communication 10 rapid 11 and 11 and 12 accurate 11 and 13 communication 13 communication 14 regarding 14 regarding 19 and 15 lasers 16 , 16 , 17 lights 16 , 19 and 18 , 19 and 19 and 22 devices 20 other 22 devices 21 energy 22 devices it is a truth universally acknowledged that although men tend to have better health in old age , women live longer lives . 0 ###LEFT-WALL### 1 it 0 ###LEFT-WALL### 2 is 0 ###LEFT-WALL### 23 . 1 it 2 is 2 is 4 truth 2 is 7 that 3 a 4 truth 4 truth 6 acknowledged 5 universally 6 acknowledged 7 that 19 women 7 that 20 live 8 although 9 men 8 although 10 tend 8 although 18 , 8 although 19 women 9 men 10 tend 10 tend 11 to 10 tend 12 have 11 to 12 have 12 have 14 health 12 have 15 in 13 better 14 health 15 in 17 age 16 old 17 age 19 women 20 live 20 live 22 lives 21 longer 22 lives here , we briefly review the biological , social and behavioural factors that may contribute to women 's greater longevity . 0 ###LEFT-WALL### 3 we 0 ###LEFT-WALL### 5 review 0 ###LEFT-WALL### 21 . 1 here 2 , 1 here 3 we 3 we 5 review 4 briefly 5 review 5 review 12 factors 6 the 12 factors 7 biological 8 , 7 biological 12 factors 9 social 10 and 10 and 11 behavioural 10 and 12 factors 12 factors 13 that 12 factors 14 may 13 that 14 may 14 may 15 contribute 15 contribute 16 to 16 to 20 longevity 17 women 18 's 18 's 20 longevity 19 greater 20 longevity we consider in particular factors that might result in a greater frailty burden in women , focusing on frailty being measured by a frailty index . 0 ###LEFT-WALL### 1 we 0 ###LEFT-WALL### 2 consider 0 ###LEFT-WALL### 26 . 1 we 2 consider 2 consider 4 particular 2 consider 5 factors 2 consider 22 by 3 in 4 particular 5 factors 6 that 5 factors 7 might 6 that 7 might 7 might 8 result 8 result 9 in 8 result 14 in 8 result 20 being 9 in 13 burden 10 a 13 burden 11 greater 12 frailty 12 frailty 13 burden 14 in 15 women 16 , 20 being 17 focusing 18 on 17 focusing 20 being 18 on 19 frailty 20 being 21 measured 22 by 25 index 23 a 25 index 24 frailty 25 index the frailty index represents the burden of health deficits , expressed for an individual as the proportion of deficits present - from 0 ( no deficits ) to 1.0 ( the theoretical maximum , if all deficits were expressed ) . 0 ###LEFT-WALL### 3 index 0 ###LEFT-WALL### 4 represents 0 ###LEFT-WALL### 41 . 1 the 3 index 2 frailty 3 index 3 index 4 represents 4 represents 6 burden 5 the 6 burden 6 burden 7 of 7 of 9 deficits 8 health 9 deficits 9 deficits 11 expressed 10 , 11 expressed 11 expressed 12 for 11 expressed 15 as 11 expressed 40 ) 12 for 14 individual 13 an 14 individual 15 as 17 proportion 16 the 17 proportion 17 proportion 18 of 18 of 19 deficits 19 deficits 20 present 20 present 22 from 20 present 28 to 20 present 35 if 21 - 22 from 22 from 23 0 22 from 27 ) 23 0 26 deficits 24 ( 26 deficits 25 no 26 deficits 26 deficits 27 ) 28 to 29 1.0 29 1.0 33 maximum 30 ( 33 maximum 31 the 33 maximum 32 theoretical 33 maximum 33 maximum 34 , 34 , 35 if 35 if 37 deficits 35 if 39 expressed 35 if 40 ) 36 all 37 deficits 37 deficits 38 were 38 were 39 expressed 39 expressed 40 ) a greater frailty burden in women might first represent a male " [fitness] - frailty pleiotropy " , resulting in men having lower physiological reserves in old age so that health deficits are more lethal . 0 ###LEFT-WALL### 4 burden 0 ###LEFT-WALL### 9 represent 1 a 4 burden 2 greater 3 frailty 3 frailty 4 burden 4 burden 5 in 4 burden 7 might 5 in 6 women 7 might 9 represent 8 first 9 represent 9 represent 16 pleiotropy 9 represent 19 resulting 10 a 11 male 10 a 16 pleiotropy 11 male 12 " 11 male 14 - 11 male 16 pleiotropy 15 frailty 16 pleiotropy 16 pleiotropy 17 " 18 , 19 resulting 19 resulting 20 in 19 resulting 36 . 20 in 21 men 21 men 22 having 22 having 25 reserves 22 having 26 in 22 having 30 that 23 lower 25 reserves 24 physiological 25 reserves 26 in 28 age 27 old 28 age 29 so 30 that 30 that 32 deficits 30 that 33 are 31 health 32 deficits 32 deficits 33 are 33 are 35 lethal 34 more 35 lethal