Enhanced Autophagy and Reduced Expression of Cathepsin D Are Related to Autophagic Cell Death in Epstein-Barr Virus-Associated Nasal Natural Killer/T-Cell Lymphomas: An Immunohistochemical Analysis of Beclin-1, LC3, Mitochondria (AE-1), and Cathepsin D in Nasopharyngeal Lymphomas

This study investigated autophagy in 37 cases of nasopharyngeal lymphomas including 23 nasal natural killer (NK)/T-cell lymphomas (NKTCL), 3 cytotoxic T-cell lymphomas (cytotoxic-TML) and 9 B-cell lymphomas (BML) by means of antigen-retrieval immunohistochemistry of beclin-1, LC3, mitochondria (AE-1) and cathepsin D. Peculiar necrosis was noted in EBV+ lymphomas comprising 21 NKTCL, 2 cytotoxic-TML and 1 BML. Lymphomas without peculiar necrosis showed high expression of beclin-1, macrogranular cytoplasmal stain of LC3 with sporadic nuclear stain, a hallmark of autophagic cell death (ACD), some aggregated mitochondria and high expression of cathepsin D, suggesting a state of growth with enhanced autophagy with sporadic ACD. EBV+ NKTCL with the peculiar necrosis, showed significantly low level of macrogranular staining of LC3, aggregated mitochondria and low expression of cathepsin D in the cellular areas when degenerative lymphoma cells showed decreased beclin-1, significantly advanced LC3-labeled autophagy, residual aggregated mitochondria and significantly reduced expression of cathepsin D, suggesting advanced autophagy with regional ACD. Consequently it was suggested that enhanced autophagy and reduced expression of lysosomal enzymes induced regional ACD under EBV infection in NKTCL

Insufficiency of phosphatidylethanolamine N-methyltransferase is risk for lean non-alcoholic steatohepatitis

　Although obesity is undoubtedly major risk for non-alcoholic steatohepatitis (NASH), the presence of lean NASH patients with normal body mass index has been recognized. Here, we report that the insufficiency of phosphatidylethanolamine N-methyltransferase (PEMT) is a risk for the lean NASH. The Pemt−/− mice fed high fat-high sucrose (HFHS) diet were protected from diet-induced obesity and diabetes, while they demonstrated prominent steatohepatitis and developed multiple liver tumors. Pemt exerted inhibitory effects on p53-driven transcription by forming the complex with clathrin heavy chain and p53, and Pemt−/− mice fed HFHS diet demonstrated prominent apoptosis of hepatocytes. Furthermore, hypermethylation and suppressed mRNA expression of F-box protein 31 and hepatocyte nuclear factor 4α resulted in the prominent activation of cyclin D1. PEMT mRNA expression in liver tissues of NASH patients was significantly lower than those with simple steatosis and we postulated the distinct clinical entity of lean NASH with insufficiency of PEMT activities

High Mortality in an Older Japanese Population with Low Forced Vital Capacity and Gender-Dependent Potential Impact of Muscle Strength: Longitudinal Cohort Study

Generally, weak muscle power is associated with high mortality. We aimed to evaluate the unknown association between % predicted value forced vital capacity (FVC% predicted) and mortality in asymptomatic older people, and the impact of muscle power on this association. We analyzed the Tsurugaya cohort that enrolled Japanese people aged ≥70 for 15 years with Cox proportional hazards model. Exposure variables were FVC% predicted and leg power. The outcome was all-cause mortality. The subjects were divided into quartiles by FVC% predicted or leg power, or into two groups by 80% for FVC% predicted or by the strongest 25% for leg power. Across 985 subjects, 262 died. The males with lower FVC% predicted exhibited higher mortality risks. The hazard ratio (HR) was 2.03 (95% CI 1.30–3.18) at the lowest relative to the highest groups. The addition of leg power reduced the HR to 1.78 (95% CI 1.12–2.80). In females, FVC% predicted under 80% was a risk factor and the HR was 1.67 (95% CI 1.05–2.64) without the effect of leg power. In FVC% predicted <80% males HRs were 2.44 (95% CI 1.48–4.02) in weak and 1.38 (95% CI 0.52–3.64) in strong leg power males, relative to ≥80% and strong leg power males. Low FVC% predicted was associated with high mortality with potential unfavorable effects of weak leg power in males

Association between Timing of Epinephrine Administration and Outcomes of Traumatic Out-of-Hospital Cardiac Arrest following Traffic Collisions

The effects of epinephrine administration timing on patients with out-of-hospital cardiac arrest (OHCA) following traffic collisions are unknown. We analyzed the 2013–2019 All-Japan Utstein Registry data of 2024 such patients aged ≥18 years who were resuscitated by emergency medical service (EMS) personnel or bystanders and then transported to medical institutions. Time from 119 call to epinephrine administration was classified into quartiles: Q1 (6–21 min), Q2 (22–26 min), Q3 (27–34 min), and Q4 (35–60 min). Multivariable logistic regression analysis was used to assess the effects of epinephrine administration timing on one-month survival after OHCA. Overall, the one-month survival rates were 3.2% (15/466) in Q1, 1.1% (5/472) in Q2, 1.9% (11/577) in Q3, and 0.2% (1/509) in Q4. Additionally, the one-month survival rate decreased significantly in the Q4 group (adjusted odds ratio, 0.07; 95% confidence interval, 0.01–0.57) compared with the Q1 group, and the probability of one-month survival decreased as the time from the EMS call to epinephrine administration increased (p-value for trend = 0.009). Only four patients (0.9% [4/466]) with the earliest epinephrine administration showed a good neurological outcome

Japanese Diet and Mortality, Disability, and Dementia: Evidence from the Ohsaki Cohort Study

The Japanese dietary pattern has long been discussed as one of the factors behind the longevity of Japanese people. However, the health benefits of the Japanese dietary pattern have not been fully elucidated. We published the first report in the world regarding the relation between the Japanese dietary pattern and cardiovascular disease mortality in 2007 using cohort studies including Japanese residents of Ohsaki City, Miyagi Prefecture, Japan. Since then, we have developed the Japanese Diet Index (JDI) that was based on previous findings to assess the degree of the Japanese dietary pattern and to advance the evidence on the health effects of the Japanese dietary pattern. So far, we have explored the associations between the JDI score (in quartiles) and various outcomes. For all-cause mortality, in comparison to Q1 (the lowest), the multivariable hazard ratios (HRs) and 95% confidence intervals (95%CIs) were 0.92 (0.85–1.00) for Q2, 0.91 (0.83–0.99) for Q3, and 0.91 (0.83–0.99) for Q4 (the highest). For functional disability, the multivariable HRs (95%CIs) were 0.94 (0.81–1.09) for Q2, 0.90 (0.77–1.05) for Q3, and 0.79 (0.68–0.92) for Q4. For dementia, the multivariable HRs (95%CIs) were 0.88 (0.74–1.05) for Q2, 0.87 (0.73–1.04) for Q3, 0.79 (0.66–0.95) for Q4. In addition, people with higher adherence to the Japanese dietary pattern also showed decreases in disability and dementia risks. The purpose of this article was to review all six papers, summarize the health effects of the Japanese dietary pattern, and discuss implications for future research

Experiences of patients with HIV/AIDS receiving mid- and long-term care in Japan: A qualitative study

Purpose: In the era of antiretroviral treatment (ART), treatment of HIV has become more manageable, and most patients with HIV benefit from long-term therapy in Japan. The aim of this qualitative study was to examine the experiences of patients with HIV/AIDS receiving mid- and long-term care in Japan. Methods: A qualitative study was performed using semi-structured interviews at an outpatient clinic of a university hospital in the Greater Tokyo area. A total of 31 Japanese patients with HIV who had been receiving treatment for at least a year were interviewed in Japanese. Data from these interviews were analyzed by ‘content analysis’ (Krippendorff, 1980). Results: The data were organized into the following seven themes: “feelings toward diagnosis of HIV infection”; “perceptions and behavior after diagnosis of HIV”; “attitudes toward HIV therapy”; “fear and hope for the future”; “feelings toward professional support”; “life changes after HIV therapy”; and “struggles in relationships with others”. Conclusions: Some participants accepted themselves as HIV-positive, some did not when they were diagnosis. This difference of reaction had effect on attitudes toward HIV therapy. But all participants continued mid- and long-treatments owing to feeling well and receiving support from professionals. Additionally, it found that patients were felt stigma of HIV-positive similarly to another Asian countries. Therefore, we should provide the entire Japanese society with knowledge about HIV/AIDS and be early and constant intervention by professional teams after being infected

Effect of a financial incentive (shopping point) on increasing the number of daily walking steps among community-dwelling adults in Japan: a randomised controlled trial

Objective The aim of this study was to investigate the effect of a financial incentive on the number of daily walking steps among community-dwelling adults in Japan.Study design Two-arm, parallel-group randomised controlled trial.Setting/participants We recruited physically inactive community-dwelling adults from Sendai city, Japan. Eligible participants were randomly allocated to an intervention or a wait list control group. Pedometers were used to assess the mean number of daily steps in three periods: baseline (weeks 1–3), intervention (weeks 4–6) and follow-up (weeks 7–9).Intervention The intervention group was offered a financial incentive (shopping points) to meet the target number of increased daily steps in the intervention period.Main outcome measures The primary outcome was an increase in the mean number of daily steps in the intervention and follow-up periods compared with baseline.Results Seventy-two participants (69.4% women; mean age, 61.2±16.2 years; mean number of daily steps at baseline, 6364±2804) were randomised to the intervention (n=36) and control groups (n=36). During the intervention period, the increase in mean daily steps was significantly higher in the intervention group (1650, 95% CI=1182 to 2119) than in the control group (514, 95% CI=136 to 891; p<0.001). However, the difference between groups was not significant at follow-up after the incentives were removed (p=0.311). In addition, compared with controls, a significantly higher proportion of participants in the intervention group showed an increase in mean daily steps of ≥1000 (69.4% vs 30.6%, respectively; OR=5.17, 95% CI=1.89 to 14.08). There were no adverse effects from the intervention.Conclusions The present results suggest that financial incentives are effective in promoting short-term increases in physical activity.Trial registration number UMIN000033276

Association of Sleep Duration with All- And Major-Cause Mortality among Adults in Japan, China, Singapore, and Korea

Importance: The association between long sleep duration and mortality appears stronger in East Asian populations than in North American or European populations.Objectives: To assess the sex-specific association between sleep duration and all-cause and major-cause mortality in a pooled longitudinal cohort and to stratify the association by age and body mass index.Design, Setting, and Participants: This cohort study of individual-level data from 9 cohorts in the Asia Cohort Consortium was performed from January 1, 1984, to December 31, 2002. The final population included participants from Japan, China, Singapore, and Korea. Mean (SD) follow-up time was 14.0 (5.0) years for men and 13.4 (5.3) years for women. Data analysis was performed from August 1, 2018, to May 31, 2021. Exposures: Self-reported sleep duration, with 7 hours as the reference category.Main Outcomes and Measures: Mortality, including deaths from all causes, cardiovascular disease, cancer, and other causes. Sex-specific hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards regression with shared frailty models adjusted for age and the key self-reported covariates of marital status, body mass index, smoking status, alcohol consumption, physical activity, history of diabetes and hypertension, and menopausal status (for women).Results: For 322721 participants (mean [SD] age, 54.5 [9.2] years; 178542 [55.3%] female), 19419 deaths occurred among men (mean [SD] age of men, 53.6 [9.0] years) and 13768 deaths among women (mean [SD] age of women, 55.3 [9.2] years). A sleep duration of 7 hours was the nadir for associations with all-cause, cardiovascular disease, and other-cause mortality in both men and women, whereas 8 hours was the mode sleep duration among men and the second most common sleep duration among women. The association between sleep duration and all-cause mortality was J-shaped for both men and women. The greatest association for all-cause mortality was with sleep durations of 10 hours or longer for both men (hazard ratio [HR], 1.34; 95% CI, 1.26-1.44) and women (HR, 1.48; 95% CI, 1.36-1.61). Sex was a significant modifier of the association between sleep duration and mortality from cardiovascular disease (χ25 = 13.47, P =.02), cancer (χ25 = 16.04, P =.007), and other causes (χ25 = 12.79, P =.03). Age was a significant modifier of the associations among men only (all-cause mortality: χ25 = 41.49, P 25 = 24.51, P Conclusions and Relevance: The findings of this cohort study suggest that sleep duration is a behavioral risk factor for mortality in both men and women. Age was a modifier of the association between sleep duration in men but not in women. Sleep duration recommendations in these populations may need to be considered in the context of sex and age.</p

Association of Sleep Duration with All- And Major-Cause Mortality among Adults in Japan, China, Singapore, and Korea

Importance: The association between long sleep duration and mortality appears stronger in East Asian populations than in North American or European populations. Objectives: To assess the sex-specific association between sleep duration and all-cause and major-cause mortality in a pooled longitudinal cohort and to stratify the association by age and body mass index. Design, Setting, and Participants: This cohort study of individual-level data from 9 cohorts in the Asia Cohort Consortium was performed from January 1, 1984, to December 31, 2002. The final population included participants from Japan, China, Singapore, and Korea. Mean (SD) follow-up time was 14.0 (5.0) years for men and 13.4 (5.3) years for women. Data analysis was performed from August 1, 2018, to May 31, 2021. Exposures: Self-reported sleep duration, with 7 hours as the reference category. Main Outcomes and Measures: Mortality, including deaths from all causes, cardiovascular disease, cancer, and other causes. Sex-specific hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards regression with shared frailty models adjusted for age and the key self-reported covariates of marital status, body mass index, smoking status, alcohol consumption, physical activity, history of diabetes and hypertension, and menopausal status (for women). Results: For 322721 participants (mean [SD] age, 54.5 [9.2] years; 178542 [55.3%] female), 19419 deaths occurred among men (mean [SD] age of men, 53.6 [9.0] years) and 13768 deaths among women (mean [SD] age of women, 55.3 [9.2] years). A sleep duration of 7 hours was the nadir for associations with all-cause, cardiovascular disease, and other-cause mortality in both men and women, whereas 8 hours was the mode sleep duration among men and the second most common sleep duration among women. The association between sleep duration and all-cause mortality was J-shaped for both men and women. The greatest association for all-cause mortality was with sleep durations of 10 hours or longer for both men (hazard ratio [HR], 1.34; 95% CI, 1.26-1.44) and women (HR, 1.48; 95% CI, 1.36-1.61). Sex was a significant modifier of the association between sleep duration and mortality from cardiovascular disease (χ25= 13.47, P =.02), cancer (χ25= 16.04, P =.007), and other causes (χ25= 12.79, P =.03). Age was a significant modifier of the associations among men only (all-cause mortality: χ25= 41.49, P <.001; cancer: χ25= 27.94, P <.001; other-cause mortality: χ25= 24.51, P <.001). Conclusions and Relevance: The findings of this cohort study suggest that sleep duration is a behavioral risk factor for mortality in both men and women. Age was a modifier of the association between sleep duration in men but not in women. Sleep duration recommendations in these populations may need to be considered in the context of sex and age

Association of Marital Status With Total and Cause-Specific Mortality in Asia

Importance: Marital status has been shown to be associated with mortality, but evidence in Asian populations is limited. Objective: To examine the association of marital status with total and cause-specific mortality.Design, Setting, and Participants: This cohort study included individual participant data from 16 prospective studies in the Asia Cohort Consortium conducted between 1963 and 2015. Asian participants with complete information on marital and vital status were included. Study-specific hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards model and then pooled using a random-effects meta-analysis. The analysis began in February 2021 and ended in August 2021. Exposures: Marital status.Main Outcomes and Measures: All-cause and cause-specific mortality.Results: Of 623140 participants (326397 women [52.4%] and 296743 men [47.6%]; mean [SD] age, 53.7 [10.2] years; mean [SD] follow-up time, 15.5 [6.1] years), 123264 deaths were ascertained. Compared with married individuals, those who were unmarried had pooled HRs of 1.15 (95% CI, 1.07-1.24) for total mortality, 1.12 (95% CI, 1.03-1.22) for cerebrovascular disease mortality, 1.20 (95% CI, 1.09-1.31) for coronary heart disease mortality, 1.17 (95% CI, 1.07-1.28) for circulatory system diseases mortality, 1.06 (95% CI, 1.01-1.11) for cancer mortality, 1.14 (95% CI, 1.05-1.23) for respiratory diseases mortality, and 1.19 (95% CI, 1.05-1.34) for external causes of death. Positive associations with total mortality were also observed for those who were single (HR, 1.62; 95% CI, 1.41-1.86), separated (HR, 1.35; 95% CI, 1.13-1.61), divorced (HR, 1.38; 95% CI, 1.13-1.69), and widowed (HR, 1.09; 95% CI, 1.04-1.13). In subgroup analyses, the positive association persisted across baseline health conditions, and the risk of death was more pronounced among men or people younger than 65 years.Conclusions and Relevance: This large pooled cohort study of individual participant data provides strong evidence that being unmarried, as well as belonging to the unmarried subcategories, was positively associated with total and cause-specific mortality. Investment of targeted social support services might need to be considered in light of the mortality differences between married and unmarried individuals.</p