Effect of an Internet-Delivered Cognitive Behavioral Therapy-Based Sleep Improvement App for Shift Workers at High Risk of Sleep Disorder: Single-Arm, Nonrandomized Trial.

BACKGROUND: Shift workers are at high risk of developing sleep disorders such as shift worker sleep disorder or chronic insomnia. Cognitive behavioral therapy (CBT) is the first-line treatment for insomnia, and emerging evidence shows that internet-based CBT is highly effective with additional features such as continuous tracking and personalization. However, there are limited studies on internet-based CBT for shift workers with sleep disorders. OBJECTIVE: This study aimed to evaluate the impact of a 4-week, physician-assisted, internet-delivered CBT program incorporating machine learning-based well-being prediction on the sleep duration of shift workers at high risk of sleep disorders. We evaluated these outcomes using an internet-delivered CBT app and fitness trackers in the intensive care unit. METHODS: A convenience sample of 61 shift workers (mean age 32.9, SD 8.3 years) from the intensive care unit or emergency department participated in the study. Eligible participants were on a 3-shift schedule and had a Pittsburgh Sleep Quality Index score ≥5. The study comprised a 1-week baseline period, followed by a 4-week intervention period. Before the study, the participants completed questionnaires regarding the subjective evaluation of sleep, burnout syndrome, and mental health. Participants were asked to wear a commercial fitness tracker to track their daily activities, heart rate, and sleep for 5 weeks. The internet-delivered CBT program included well-being prediction, activity and sleep chart, and sleep advice. A job-based multitask and multilabel convolutional neural network-based model was used for well-being prediction. Participant-specific sleep advice was provided by sleep physicians based on daily surveys and fitness tracker data. The primary end point of this study was sleep duration. For continuous measurements (sleep duration, steps, etc), the mean baseline and week-4 intervention data were compared. The 2-tailed paired t test or Wilcoxon signed rank test was performed depending on the distribution of the data. RESULTS: In the fourth week of intervention, the mean daily sleep duration for 7 days (6.06, SD 1.30 hours) showed a statistically significant increase compared with the baseline (5.54, SD 1.36 hours; P=.02). Subjective sleep quality, as measured by the Pittsburgh Sleep Quality Index, also showed statistically significant improvement from baseline (9.10) to after the intervention (7.84; P=.001). However, no significant improvement was found in the subjective well-being scores (all P>.05). Feature importance analysis for all 45 variables in the prediction model showed that sleep duration had the highest importance. CONCLUSIONS: The physician-assisted internet-delivered CBT program targeting shift workers with a high risk of sleep disorders showed a statistically significant increase in sleep duration as measured by wearable sensors along with subjective sleep quality. This study shows that sleep improvement programs using an app and wearable sensors are feasible and may play an important role in preventing shift work-related sleep disorders. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/24799.

Substrate stiffness modulates endothelial cell function via the YAP-Dll4-Notch1 pathway.

Endothelial cells adapt their functions as a consequence of sensing extracellular substrate stiffness; these alterations allow them to maintain their vascular structure and function. Substrate stiffness-mediated yes-associated protein 1 (YAP) activation plays an important role in mechano-transduction and pro-angiogenic phenotype of endothelial cells, and Delta-like ligand 4 (Dll4)-Notch1 signaling is closely related to angiogenesis; however, the impact of substrate stiffness-mediated interrelation of these pathways on endothelial cell functions remains elusive. We confirmed that endothelial cells on softer substrates not only elongate cellular aspects but also attenuate YAP activation compared to cells on stiffer substrates. Endothelial cells on softer substrates also upregulate the vascular endothelial growth factor receptor 1 (VEGFR1) and VEGFR2 mRNA expression that is enhanced by VEGF stimulation. We determined that endothelial cells on softer substrates increased Dll4 expression, but not Notch1 expression, via YAP signaling. Moreover, endothelial cells on soft substrates induced not only VEGFRs upregulation but also suppression of pro-inflammatory interleukin-6 and plasminogen activator inhibitor-1 mRNA expression and the facilitation of anti-coagulant thrombomodulin and pro-coagulant tissue factor mRNA expression. Our results suggest that endothelial cells activate the YAP-Dll4-Notch signaling pathway in response to substrate stiffness and dictate cellular function.

[Cross-sectional and longitudinal associations of physical performance and skeletal muscle mass with cognition and cognitive decline among community-dwelling older Japanese].

AIM: This study had two objectives: to confirm the cross-sectional associations between the physical performance scale (PPS), skeletal muscle mass (SMM) and sarcopenia and cognition, and to examine whether PPS, SMM and sarcopenia are independent risk markers of cognitive decline (CD). METHODS: Among 805 adults 65 years of age or older who participated in a baseline survey (2008-2011), 649 were reevaluated for their level of cognition at least once until 2012, and PPS, SMM, sarcopenia and cognition were assessed. CD was defined as a decrease of at least 0.5 points per year on the MMSE. RESULTS: After controlling for sex, age and years of education, PPS, SMM and sarcopenia were associated with cognition, respectively. During a median follow-up of 3.0 years, 201 adults (31.0%) had CD. After controlling for important confounders, PPS showed a significant association with CD [OR=0.75 (95%CI: 0.65-0.87)], whereas SMM showed no significant association with CD. As compared with the people who had normal PPS and SMM, people who had low PPS and normal SMM had 2.10 times higher risk for CD. CONCLUSIONS: We confirmed the cross-sectional associations between physical performance, SMM and sarcopenia and cognition in a general population of older adults. Although people had normal SMM, low physical performance was found to be a risk marker for subsequent CD.

[Prospective study of cognitive decline assessed using the mini-mental state examination and the risk of incident long-term care insurance among community-dwelling older Japanese].

AIM: We examined the longitudinal association between the change in the Mini-Mental State Examination (MMSE) score per year and the incidence of a certified need for care in the long-term care insurance system among community-dwelling older Japanese subjects. METHODS: A total of 773 adults 65 years of age or older who participated in a baseline survey (2002 to 2007) underwent MMSE reevaluation at least once until Wave-1 (2003 to 2008). The incidence of a certified need for care in the long-term care insurance system until Wave-2 (Wave-1 to 2013) was examined in all subjects. RESULTS: During an average follow-up of 1,195 days (baseline survey to Wave-1), the change in the MMSE score per year was greater than 0 in 511 (66.1%) participants, 0 to -0.5 in 94 (12.2%) participants, -0.5 to -1 in 66 (8.5%) participants, -1 to -2 in 56 (7.2%) participants, and less than -2 in 46 (6.0%) participants. During an average follow-up of 1,802 days (Wave-1 to Wave-2), 104 participants (13.5%) were newly certified with a need for care in the long-term care insurance system. After controlling for important confounders, elders with a change in the MMSE score of 0 to -0.5, -0.5 to -1, -1 to -2 and less than -2 per year were 1.73 (95% confidence interval, 0.93-3.23), 1.94 (1.01-3.45), 1.95 (1.02-3.76) and 3.16 (1.68-5.98) times as likely to be newly certified with a need for care in the long-term care insurance system, respectively, compared those with a change in the score greater than 0. CONCLUSIONS: The extent of change in the MMSE score per year independently predicted the incident certified need for care in the long-term care insurance system in a general population of older Japanese subjects. A decrease of greater than 0.5 points per year may be a useful cutoff value for clinically evaluating elders.

Tri-Axial Accelerometer-Determined Daily Physical Activity and Sedentary Behavior of Suburban Community-Dwelling Older Japanese Adults.

Knowledge regarding accelerometer-derived physical activity (PA) and sedentary behavior (SED) levels is scarce for Japanese older adults. The aims of this study were therefore to 1) describe levels of PA and SED in Japanese community-dwelling older adults, using tri-axial accelerometer; 2) examine the variation of PA and SED with respect to sex, age, and body mass index (BMI). Participants of this study were from the baseline survey of the Sasaguri Genkimon Study, who were 65 years or older and not certified as those requiring long-term care. PA was assessed objectively for seven consecutive days using tri-axial accelerometer. A total of 1,739 participants (median age: 72 years, men: 38.0%) with valid PA data were included. Overall, participants in the present study spent 54.5% of their waking time being sedentary and 45.5% being active, of which 5.4% was moderate-to-vigorous physical activity (MVPA). Women accumulated more minutes of light physical activity (LPA) and MVPA compared with men. In contrast, men spent more time being sedentary. Mean steps per day did not differ between sexes. Furthermore, participants with higher BMI (BMI ≥25) had lower PA levels, and longer SED compared with those with lower BMI (BMI <). PA levels were lower and SED was longer with age. The present study is the first to demonstrate that the levels of PA and SED differed by sex, age, and BMI in Japanese community-dwelling older adults. In particular, women were more active compared with men, providing unique insight into the current level of PA in older adults. Data presented in the study will enable further investigation of additional determinants of PA and SED in order to develop effective population-based intervention strategies to promote PA and reduce prolonged SED in the Japanese population and possibly other rapidly aging societies. Key pointsAccelerometer, that is capable to assess PA more precisely in large scale epidemiological studies, provides opportunity for improving understanding of daily PA in older adults.This study first demonstrated that the levels of PA and SED differed by sex, age, and BMI in Japanese community-dwelling older people.Women were more active compared with men, in terms of more minutes of MVPA.

The Yabu cohort study: design and profile of participants at baseline.

BACKGROUND: Further evidence into the effects of social relationships on health (including those at both the individual and community levels) is needed in Japan. The Yabu Cohort Study was launched in 2012 to identify the associations between social relationships and health among community-dwelling older Japanese people and to evaluate population approaches for preventive long-term care in the community. This report describes the study design and the profile of the participants at baseline. METHODS: The Yabu Cohort Study is a prospective study of community-dwelling individuals aged 65 years and older in Yabu, Hyogo Prefecture, Japan. The baseline survey, using a mailed self-administered questionnaire, was conducted from July through August 2012. It included information on socioeconomic status, general and psychological health, and social relationships (social network, social support, and social capital). Survival time, long-term care insurance certification, and medical and long-term care costs after the baseline survey will be followed. RESULTS: Of 7271 questionnaires distributed, a total of 6652 were returned (91.5% response rate), and 6241 were included in the analysis. Mean age was 71.9 ± 5.2 years, 43.2% were men, and 83.8% had lived in their neighborhood for more than 40 years. Approximately 45.2% expressed general trust. About 82.4%, 49.9%, and 55.5% have participated in neighborhood association activities, municipal seminars for preventive long-term care, and salon activities in the community, respectively. CONCLUSIONS: The study is expected to provide valuable evidence on the effects of social relationships on health and to suggest the usefulness of population approaches for preventive long-term care in Japanese communities.

[A 10-year community intervention for disability prevention and changes in physical, nutritional, psychological and social functions among community-dwelling older adults in Kusatsu, Gunma Prefecture, Japan].

OBJECTIVES: We reported previously that a 10-year community intervention for disability prevention successfully extended healthy life expectancy at 70 years and decreased the enrollment rate of the Long-Term Care Insurance in Kusatsu, Gunma Prefecture, Japan. In order to clarify functional factors that contributed to healthy aging, this study examined changes in physical, nutritional, psychological and social functions in older adults who participated in annual health checkups over the period. METHODS: Data sources were participants in annual health checkups conducted from 2002 to 2012 and respondents to biannual monitoring surveys conducted from 2003 to 2011. The target population was all older adults aged 70 years and over living in Kusatsu. The average participation rate over the period was 34.7% for the annual health checkups and 95.0% for the monitoring surveys. First, we examined the representativeness of the participants in annual health checkups by comparing them with the responders to monitoring surveys in terms of their higher-level functional capacity, as measured by the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC) (Analysis 1). Second, we examined changes in the physical (4 measures), nutritional (3 measures), and psychological and social (4 measures) functions of participants in annual health checkups over the period. In this analysis, we standardized the data for each year on 11 measures to a mean of 0 and a standard deviation of 1.0 using the 2002 data as the standard, and conducted statistical tests for the slopes of the linear approximate equation (intercept=0) (Analysis 2). RESULTS: In Analysis 1, the TMIG-IC scores for participants in the annual health checkups were significantly higher in both sexes than were those for responders to the monitoring surveys. However, there were no significant year×group interactions in the scores. The difference in scores between the two groups was small for participants in their seventies, but large for participants in their eighties or over. Analysis 2 showed that all physical functions improved significantly over the period in both sexes, and the slopes of the linear approximate equation were steeper for maximal and usual gait speeds (slope=0.050 and 0.048, respectively, in men; 0.067 and 0.060, respectively, in women) than for other measures. In women, in addition to physical function, scores on the Mini-Mental State Examination (slope=0.053), Geriatric Depression Scale (slope=0.027), and Social Roll Scale (slope=0.019) also increased significantly. CONCLUSION: Although participants in annual health checkups were biased toward better functioning, the degree of the bias did not change significantly over the period. During the same period, physical function for both sexes, and psychological and social functions for women, improved significantly. It may be concluded that functional improvement in older adults contributed to the healthy longevity in Kusatsu.

Physical Fitness Measures as Potential Markers of Low Cognitive Function in Japanese Community-Dwelling Older Adults without Apparent Cognitive Problems.

Detecting signs of cognitive impairment as early as possible is one of the most urgent challenges in preventive care of dementia. It has still been unclear whether physical fitness measures can serve as markers of low cognitive function, a sign of cognitive impairment, in older people free from dementia. The aim of the present study was to examine an association between each of five physical fitness measures and global cognition in Japanese community-dwelling older adults without apparent cognitive problems. The baseline research of the Sasaguri Genkimon Study was conducted from May to August 2011 in Sasaguri town, Fukuoka, Japan. Of the 2,629 baseline subjects who were aged 65 years or older and not certified as individuals requiring nursing care by the town, 1,552 participants without apparent cognitive problems (Mini-Mental State Examination score ≥24) were involved in the present study (59.0% of the baseline subjects, median age: 72 years, men: 40.1%). Global cognitive function was measured by the Japanese version of the Montreal Cognitive Assessment. Handgrip strength, leg strength, sit-to-stand rate, gait speed, and one-leg stand time were examined as physical fitness measures. In multiple linear regression analyses, each of the five physical fitness measures was positively associated with the Montreal Cognitive Assessment score after adjusting for age and sex (p < 0.001). These associations were preserved after additional adjustment for years of formal education, body mass index, and other confounding factors (p < 0.001). The present study first demonstrated the associations between multiple aspects of physical fitness and global cognitive function in Japanese community-dwelling older people without apparent cognitive problems. These results suggest that each of the physical fitness measures has a potential as a single marker of low cognitive function in older populations free from dementia and thereby can be useful in community-based preventive care of dementia. Key pointsThere is a great need for identifying lifestyle-related markers which help detect subtle cognitive impairment in the preclinical or earlier phase of dementia.In the present study, each of the five physical fitness measures employed was linearly and positively associated with the Montreal Cognitive Assessment score in the present older adults without apparent cognitive problems, after adjusting for age, sex, education, body mass index, and other confounding factors.The results suggest the potential of each physical fitness measure as a single lifestyle-related marker of low cognitive function in the population, which can be useful in community-based preventive care of dementia.

Normative data for the montreal cognitive assessment in a Japanese community-dwelling older population.

BACKGROUND: Although the Montreal Cognitive Assessment (MoCA) is acknowledged as a promising neuropsychological tool, its normative data for older populations have not been established yet. The purpose of this study was to provide normative data for the MoCA in Japanese community-dwelling older people. METHODS: In a Japanese town, 1,977 participants aged 65 years or older (mean age 73.6 years; male 41.3%) completed MoCA tests. After descriptive and regression analyses, normative data were developed for MoCA scores in the population. RESULTS: The mean MoCA score observed (21.8 points) was lower than that for normal controls (27.4 points) in the original validation study of the MoCA. Additionally, 82.6% of MoCA scores fell below the standard cutoff of 26 points for detecting mild cognitive impairment (MCI). The regression analysis showed that higher age and fewer years of formal education were associated with lower MoCA scores (p < 0.001). Normative data for MoCA scores were presented with respect to age and education. CONCLUSION: This study provided normative data for the MoCA in a Japanese community-dwelling older population. This research also suggests that conventional use of the MoCA as a screening tool for MCI might be problematic in cultures different from that in which the cutoff was developed.

The Spike Glycoprotein of SARS-CoV-2 Binds to ß1 Integrins Expressed on the Surface of Lung Epithelial Cells.

The spike glycoprotein attached to the envelope of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to and exploits angiotensin-converting enzyme 2 (ACE2) as an entry receptor to infect pulmonary epithelial cells. A subset of integrins that recognize the arginyl-glycyl-aspartic acid (RGD) sequence in the cognate ligands has been predicted in silico to bind the spike glycoprotein and, thereby, to be exploited for viral infection. Here, we show experimental evidence that the ß1 integrins predominantly expressed on human pulmonary epithelial cell lines and primary mouse alveolar epithelial cells bind to this spike protein. The cellular ß1 integrins support adhesive interactions with the spike protein independently of ACE2, suggesting the possibility that the ß1 integrins may function as an alternative receptor for SARS-CoV-2, which could be targeted for the prevention of viral infections.

Prospective Study of Trajectories of Physical Performance and Mortality Among Community-Dwelling Older Japanese.

OBJECTIVE: Physical performance measures (PPMs) are good predictors of adverse health outcomes in later life. This prospective study used repeated measures analysis to examine sex-specific age trends in PPMs, identify potential PPM trajectory patterns, and determine whether PPM trajectory patterns were associated with all-cause mortality among older Japanese. METHODS: Among 1,524 adults aged 65 years or older who participated in a baseline survey, 1,048 adults (mean [SD] age, 71.6 [5.4] years; women, 57.0%) were followed up at least once. The total number of observations was 4,747, and the average number of follow-up assessments was 4.5 during the period from 2002 through 2011. The PPMs studied were handgrip strength, usual gait speed, and one-leg standing time. We checked local registries to identify deaths from any cause; 89 (8.5%) participants died during follow-up. RESULTS: All PPMs significantly decreased with advancing age, and handgrip strength and usual gait speed showed sex-specific age trends. We identified three distinct trajectory patterns (high, middle, and low trajectory groups) for each PPM in adults aged 65-90 years, and the trajectories for handgrip strength and usual gait speed showed parallel declines in men and women, respectively. After adjusting for important confounders, the trajectory groups for handgrip strength and one-leg standing time were independent predictors of all-cause mortality. CONCLUSIONS: Regardless of baseline level, the PPMs tended to show similar age-related changes in later life. However, individuals in low PPM trajectory groups had a higher mortality risk, which highlights the importance of interventions that maintain or improve physical performance, even among older adults with low physical performance.

Are neighborhood bonding and bridging social capital protective against depressive mood in old age? A multilevel analysis in Japan.

While the importance of distinguishing between bonding and bridging social capital is now understood, evidence remains sparse on their contextual effects on health. We examined the associations of neighborhood bonding and bridging social capital with depressive mood among older Japanese. A questionnaire survey of all community residents aged 65 and older in the city of Yabu, Hyogo Prefecture, Japan was conducted in July and August 2012. Bonding and bridging social capital were assessed by evaluating individual homogeneous and heterogeneous social networks in relation to age, gender, and socioeconomic status. Individual responses in each neighborhood were aggregated to create an index of neighborhood-level bonding/bridging social capital. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the associations of such social capital with depressive mood using multilevel binomial logistic regression analysis. Of the 7271 questionnaires distributed, 6416 were analyzed (covering 152 administrative neighborhoods). Approximately 56.8% of respondents were women, and the mean age was 76.2 ± 7.1 years. Neighborhood-level bonding social capital was inversely associated with depressive mood (OR = 0.84, 95% CI = 0.75-0.94), but neighborhood-level bridging social capital was not. Gender-stratified analysis revealed that neighborhood-level bonding social capital was inversely associated with depressive mood in both genders (OR = 0.83, 95% CI = 0.72-0.96 for men; OR = 0.85, 95% CI = 0.72-0.99 for women), while neighborhood-level bridging social capital was positively associated with depressive mood in women (OR = 1.15, 95% CI = 1.00-1.34). There was also a significant interaction between individual- and neighborhood-level bonding social capital, indicating that people with a weaker homogeneous network and living in a neighborhood with weaker bonding social capital were more likely to have depressive mood. Our results suggest that neighborhood social capital does not necessarily benefit mental health in old age. These findings might stimulate further discussion on the relationship of bonding and bridging social capital with mental health.

Longitudinal association between neighborhood cohesion and depressive mood in old age: A Japanese prospective study.

Despite increasing evidence of the relationship between neighborhood cohesion and depressive mood, little is known about this longitudinal association in old age. This study examined the association between perceived neighborhood cohesion and depressive mood and the stress-buffering effect of perceived neighborhood cohesion on depressive mood among older Japanese people using the 2010 (baseline) and 2012 (follow-up) Hatoyama Cohort Study datasets. We analyzed 655 participants aged 65-84 at baseline. Although perceived neighborhood cohesion at baseline was not associated with depressive mood at follow-up, high neighborhood cohesion partially offset the deleterious effect of anticipated daily stressors on depressive mood. This effect was stronger for long-term residents of the neighborhood. Interventions to strengthen neighborhood cohesion may help reduce the deleterious effect of stressors on older residents' depressive mood.

Do bonding and bridging social capital affect self-rated health, depressive mood and cognitive decline in older Japanese? A prospective cohort study.

Little is known regarding the longitudinal effects of bonding and bridging social capital on health. This study examined the longitudinal associations of bonding and bridging social capital with self-rated health, depressive mood, and cognitive decline in community-dwelling older Japanese. Data analyzed in this study were from the 2010 (baseline) and 2012 (follow-up) Hatoyama Cohort Study. Bonding social capital was assessed by individual perception of homogeneity of the neighborhood (the level of homogeneity among neighbors) and of networks (the amount of homogeneous personal networks) in relation to age, gender, and socioeconomic status. Bridging social capital was assessed by individual perception of heterogeneity of networks (the amount of heterogeneous personal networks) in relation to age, gender, and socioeconomic status. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the effects of baseline social capital on poor health outcome at follow-up by logistic regression analysis. In total, 681 people completed baseline and follow-up surveys. The mean age of participants was 71.8 ± 5.1 years, and 57.9% were male. After adjusting for sociodemographics, lifestyle factors, comorbidity, functional capacity, baseline score of each outcome, and other bonding/bridging social capital, stronger perceived neighborhood homogeneity was inversely associated with poor self-rated health (OR = 0.55, 95% CI = 0.30-1.00) and depressive mood assessed by the Geriatric Depression Scale (OR = 0.58, 95% CI = 0.34-0.99). When participants who reported a depressive mood at baseline were excluded, stronger perceived heterogeneous network was inversely associated with depressive mood (OR = 0.40, 95% CI = 0.19-0.87). Neither bonding nor bridging social capital was significantly associated with cognitive decline assessed by the Mini-Mental State Examination. In conclusion, bonding and bridging social capital affect health in different ways, but they both have beneficial effects on the health of older Japanese. Our findings suggest that intervention focusing on bonding and bridging social capital may improve various health outcomes in old age.