Association of community-level social capital with dementia: A multilevel nine-year longitudinal study using data from the Japan Gerontological Evaluation Study.

BACKGROUND: Individual-level social capital prevents cognitive decline. However, a few studies have focused on the effects of community-level social capital on dementia. Therefore, we investigated the association between community-level social capital and dementia onset based on longitudinal study data on older adults in Japan. METHODS: We used longitudinal data from the Japan Gerontological Evaluation Study, obtained over nine years (2010-2019). In total, 35,921 physically and cognitively independent individuals (16,848 males and 19,073 females) aged ≥65 years and nested within 308 communities in seven municipalities participated in the study. Dementia onset was assessed using the public long-term care insurance registration. Social capital was assessed using three dimensions: civic participation, social cohesion, and reciprocity. We performed a two-level multilevel survival analysis stratified by sex, calculated hazard ratios (HRs), and 95% confidence intervals (CIs). RESULTS: During the follow-up, 6245 (17.4%) dementia onset cases were identified. The cumulative incidence of dementia was 16.2% in males and 18.4% in females. After adjusting for covariates, individual-level civic participation was associated with a lower incidence of dementia in both males and females (HR, 0.84; 95% CI, 0.77-0.92; HR, 0.78; 95% CI, 0.73-0.84). Community-level civic participation and social cohesion were associated with a lower incidence of dementia among females (HR, 0.96; 95% CI, 0.93-0.99; HR, 0.93; 95% CI, 0.88-0.98) and cross-level interaction on social cohesion among females (HR, 0.95; 95% CI, 0.90-0.99). CONCLUSIONS: Living in a community with high civic participation and social cohesion is associated with a lower incidence of dementia among older females. Therefore, promoting civic participation and social cohesion in the community may be a useful population-based strategy to delay or prevent the onset of dementia.

Community-level social participation and functional disability among older adults: A JAGES multilevel longitudinal study.

PURPOSE: This study investigates the contextual association between types of community-level social participation and functional disability. METHODS: We used 6-year prospective cohort data from the Japan Gerontological Evaluation Study 2010-2016, a nationwide survey of 35,519 functionally independent older adults (mean age: 73.30 ± 5.91 years, 49.6% females). The incidence of functional disability was obtained from municipal long-term care insurance databases. Social participation was assessed at individual and community levels and was categorized as: volunteer, sports, hobby and neighborhood groups, and senior citizen clubs. We calculated the 95% confidence interval (CI) and the hazard ratio (HR) by applying a three-level multilevel survival analysis. RESULTS: During the 6-year observation period, the onset of functional disability occurred among 3473 adults. A higher prevalence of sports (HR 0.88, 95% CI 0.80 to 0.96) and hobby group participation (HR 0.91, 95% CI 0.87 to 0.96) showed significant contextual relationships with functional disability after adjusting for potential confounders. Among females, community-level neighborhood group participation significantly lowered the incidence of functional disability (HR 0.87, 95% CI 0.76 to 0.998). CONCLUSIONS: We found a beneficial effect of a contextual relationship between community-level sports and hobby group participation and functional disability among older adults. Moreover, females benefited a lot from community-level social participation. We propose that promoting sports and hobby groups in a community may help to prevent functional disability among older adults.

[Effectiveness of walking point projects with incentives for walking time, physical function, and depression among older people: inverse probability of treatment weighting using propensity scores].

Objectives: This study aimed to examine the effectiveness of a walking point project with incentives for increasing walking time, preventing the decline of physical function and worsening depression among older adults. Methods: We used data from the Japan Gerontological Evaluation Study, which included subjects aged ≥65 years who lived in Yokohama City in 2013 and 2016. We obtained information on the subjects' participation in the "Yokohama Walking Point (YWP)," a program launched by Yokohama City in 2014, from the 2016 survey data. We excluded individuals with missing data for sex, age, walking time per day (<30, 30-59, 60-89, or ≥90 min/day), physical function (5 physical function category items on the Kihon Checklist), depression (15-item Geriatric Depression Scale), and participation status in the YWP. We used data from 4,509 eligible respondents. Changes in walking time, physical function, and depression were designated as dependent variables, and participation status in the YWP was designated as the independent variable in the multiple regression analysis with inverse probability of treatment weighting (IPTW), after adjusting for demographic variables, socioeconomic status, health status, and behavior. Results: Among the total subjects, 758 (16.8%) participated in the YWP. The IPTW method showed that participants in the YWP had significantly higher walking times (B=3.61, 95% CI: 1.04, 6.17), less decline in physical function, and less depression (B=-0.13, 95% CI: -0.23, -0.03; B=-0.21, 95% CI: -0.42, -0.01) than those who did not participate in the YWP. Conclusions: Our findings suggest that the YWP, with incentives, effectively increased walking time and prevented worsening of physical function and depression among older adults. The municipality's health point project, based on the number of steps, is a useful population approach for promoting health among older adults.

Does Community-Level Social Capital Predict Decline in Instrumental Activities of Daily Living? A JAGES Prospective Cohort Study.

Instrumental activities of daily living (IADL) represent the most relevant action capacity in older people with regard to independent living. Previous studies have reported that there are geographical disparities in IADL decline. This study examined the associations between each element of community-level social capital (SC) and IADL disability. This prospective cohort study conducted between 2010 and 2013 by the Japan Gerontological Evaluation Study (JAGES) surveyed 30,587 people aged 65 years or older without long-term care requirements in 380 communities throughout Japan. Multilevel logistic-regression analyses were used to determine whether association exists between community-level SC (i.e., civic participation, social cohesion, and reciprocity) and IADL disability, with adjustment for individual-level SC and covariates such as demographic variables, socioeconomic status, health status, and behavior. At three-year follow-up, 2886 respondents (9.4%) had suffered IADL disability. Residents in a community with higher civic participation showed significantly lower IADL disability (odds ratio: 0.90 per 1 standard deviation increase in civic participation score, 95% confidence interval: 0.84⁻0.96) after adjustment for covariates. Two other community-level SC elements showed no significant associations with IADL disability. Our findings suggest that community-based interventions to promote community-level civic participation could help prevent or reduce IADL disability in older people.

Correction to: Caregiver Burden and Work Productivity Among Japanese Working Family Caregivers of People with Dementia.

The authors have noted that the number of participants in the final sample should be 377, rather than 379. In this correction, the two mistaken cases were removed and analyses were repeated with 377 cases.

Caregiver Burden and Work Productivity Among Japanese Working Family Caregivers of People with Dementia.

BACKGROUND: We examined the association between caregiver burden and work productivity (i.e., absenteeism, presenteeism, and overall work impairment) among working family caregivers of people with dementia and whether job characteristics (i.e., job demands, job control, supervisor and coworker support) moderate this association. METHODS: A cross-sectional correlational study design using a web-based questionnaire survey was conducted among 379 Japanese working family caregivers of people with dementia (105 female, age range 20-77) in May 2016, which measured caregiver burden, work productivity, care situation, job characteristics, and demographics. Caregiver burden was designated as an independent variable and each aspect of work productivity as a dependent variable in a hierarchical multiple regression analysis, adjusting for demographics. Interaction terms between caregiver burden and each job characteristic were also included in the model. RESULTS: Caregiver burden was significantly and positively associated with presenteeism (ß = 0.219, p < 0.001) and overall work impairment (ß = 0.181, p < 0.001), while the association of caregiver burden with absenteeism was not significant (ß = - 0.003, p = 0.953). Interaction effects of caregiver burden × coworker support on presenteeism (ß = - 0.189, p = 0.023) and overall work impairment (ß = - 0.172, p = 0.034) were significant. According to simple slope analyses, caregiver burden was greater at lower levels of coworker support compared to higher levels of coworker support for both presenteeism and overall work impairment. CONCLUSIONS: Our study suggests that higher caregiver burden is associated with a decrease in work productivity. Additionally, coworker support appears to buffer the association of caregiver burden with presenteeism and overall work impairment among working family caregivers of people with dementia.

Long-Term Outcomes of Imatinib Treatment for Chronic Myeloid Leukemia.

BACKGROUND: Imatinib, a selective BCR-ABL1 kinase inhibitor, improved the prognosis for patients with chronic myeloid leukemia (CML). We conducted efficacy and safety analyses on the basis of more than 10 years of follow-up in patients with CML who were treated with imatinib as initial therapy. METHODS: In this open-label, multicenter trial with crossover design, we randomly assigned patients with newly diagnosed CML in the chronic phase to receive either imatinib or interferon alfa plus cytarabine. Long-term analyses included overall survival, response to treatment, and serious adverse events. RESULTS: The median follow-up was 10.9 years. Given the high rate of crossover among patients who had been randomly assigned to receive interferon alfa plus cytarabine (65.6%) and the short duration of therapy before crossover in these patients (median, 0.8 years), the current analyses focused on patients who had been randomly assigned to receive imatinib. Among the patients in the imatinib group, the estimated overall survival rate at 10 years was 83.3%. Approximately half the patients (48.3%) who had been randomly assigned to imatinib completed study treatment with imatinib, and 82.8% had a complete cytogenetic response. Serious adverse events that were considered by the investigators to be related to imatinib were uncommon and most frequently occurred during the first year of treatment. CONCLUSIONS: Almost 11 years of follow-up showed that the efficacy of imatinib persisted over time and that long-term administration of imatinib was not associated with unacceptable cumulative or late toxic effects. (Funded by Novartis Pharmaceuticals; IRIS ClinicalTrials.gov numbers, NCT00006343 and NCT00333840 .).

[An Analysis of the Controversy on the Psychoprophylaxis Method in the Japanese Medical Journal "Obstetrics and Gynecology," 1954-1957].

The methods of painless childbirth are generally divided into two kinds: "with drugs" and "without drugs." In Japan, the full-scale initiation of these two types of painless childbirth methods in clinical practice started in the early 1950s. The practice of the psychoprophylaxis method (PPM)--one of the painless childbirth methods "without drugs"--started in 1953. Japanese obstetricians had discussed the practicability of PPM for painless childbirth and had doubted the scientific nature and originality of PPM as a viable method. Therefore, they published a series of articles in the Japanese medical journal "Obstetrics and Gynecology" from 1954 to 1957. Two representative obstetricians developed this controversy. Naotaro KUJI, the director of the Central Maternity Hospital of the Japanese Red Cross Society and the chief practitioner of PPM, emphasized that PPM was a more practical method, considering the Japanese medical legal situation where midwives were prohibited to use drugs. On the other hand, Kakuichi ANDO, the chief professor of the Department of Obstetrics and Gynecology of Keio University and the team leader of the practitioners of painless childbirth "with drugs," doubted the practicability of PPM. In the course of these discussions, both groups of obstetricians gradually came to a consensus to use the concept of "pain relief" in labor, instead of "painless" childbirth. They also agreed to adopt methods "with drugs" and "without drugs," including PPM, according to the presented case.

[Introduction of the psychoprophylactic method and its influence on the prenatal care program for institutional parturition in Japan: the practice in the Central Hospital of Maternity of the Japanese Red Cross Society and Oomori Red Cross Hospital, 1953-1964].

The psychoprophylactic method is one of the methods for providing 'painless childbirth without drugs' and was invented by applying I. Pavlov's theory of higher nervous activity. In 1951, it was adopted as a national policy in the Union of Soviet Socialist Republics. This method was then introduced in the People's Republic of China in 1952. In 1953, it was brought to Japan by Masatomo SUGAI, an obstetrician, and was introduced into the Central Hospital of Maternity of the Japanese Red Cross Society with the support of the director, Naotarou KUJI. The practice of this method by the research team, which consisted of the obstetricians and midwives of the Central Hospital of Maternity of the Japanese Red Cross Society and Oomori Red Cross Hospital, resulted in the initiation and characterization of the prenatal care program to encourage the autonomy of the pregnant women for normal parturition in the institutions of Japan.

Inhibition of NF-kappa B by a cell permeable form of I kappa B alpha induces apoptosis in eosinophils.

An 11 amino acid HIV-TAT peptide can deliver target proteins into a variety of cells in a receptor-independent manner. To generate a highly specific inhibitor of the transcription factor NF-kappa B, we have fused the TAT-peptide to a version of I kappa B alpha that is resistant to signal-induced degradation. TAT-I kappa B alpha(S32A, S36A) inhibited NF-kappa B-dependent transcription in HeLa and A549 cells by retaining NF-kappa B p65 in the cytoplasm. Introduction of TAT-I kappa B alpha(S32A, S36A) into human eosinophils inhibited the nuclear translocation of NF-kappa B and induced apoptosis. Thus, continuous NF-kappa B-dependent transcription is important for eosinophil survival. While eosinophils are normally refractive to standard methods of gene delivery, the ability of TAT fusion proteins to be taken up by these cells should enable a detailed molecular analysis of survival pathways in these cells.

Inhibition of nuclear factor-kappaB activation un-masks the ability of TNF-alpha to induce human eosinophil apoptosis.

Apoptosis renders eosinophils functionally effete and marks them for "silent" removal from inflamed sites by macrophages. We show, for the first time, that eosinophils exposed to TNF-alpha rapidly lose their cytoplasmic levels of IkappaBalpha, the inhibitory subunit of NF-kappaB. Consequently, TNF-alpha triggers NF-kappaB mobilization from the cytoplasm to the nucleus, as determined by tracking the NF-kappaB subunit p65 by immunofluorescence and Western blot analysis. Inhibition of TNF-alpha-mediated IkappaBalpha degradation and NF-kappaB activation by gliotoxin or the proteasome inhibitor MG-132 un-masks the caspase-dependent pro-apoptotic properties of TNF-alpha. In addition, cycloheximide similarly renders TNF-alpha pro-apoptotic, suggesting that NF-kappaB activation controls the production of a protein(s) that protects eosinophils from the cytotoxic effects of TNF-alpha. Evidence is presented suggesting that TNF-alpha triggered apoptosis is more susceptible to NF-kappaB inhibition than constitutive apoptosis, leading to the possibility of the specific targeting of apoptosis in eosinophil sub-populations. Prior to morphological signs of apoptosis, TNF-alpha-induced IL-8 synthesis is abrogated by inhibition of NF-kappaB. We propose that NF-kappaB activation plays a critical role in controlling eosinophil responsiveness and apoptosis, and speculate that selective inhibitors of eosinophil NF-kappaB activation may ultimately provide alternative therapeutic agents for the treatment of eosinophilic diseases, including asthma and allergic rhinitis.