Efficacy and safety of romosozumab: a meta-analysis of placebo-controlled trials.

INTRODUCTION: We aimed to comprehensively compile placebo-controlled trials on the efficacy and safety of romosozumab (210 mg, subcutaneously, once monthly) in postmenopausal women and men with osteoporosis. MATERIALS AND METHODS: PubMed, Google Scholar, and ClinicalTrials.gov were searched for relevant placebo-controlled trials (as of January 1, 2024). Percent change in bone mineral density (BMD), falls, fractures, and adverse events (AEs) after drug administration were collected. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated. RESULTS: Six trials (7990 patients; follow-up period, 6-12 months) were included. Compared with placebo, romosozumab significantly increased lumbar spine BMD (MD = 12.69; 95% CI 11.10-14.29), total hip BMD (MD = 4.42; 95% CI 3.03-5.80), and femoral neck BMD (MD = 3.99; 95% CI 2.42-5.57) at 12 months. Romosozumab significantly decreased falls (RR = 0.80; 95% CI 0.68-0.93) and major osteoporotic fractures (RR = 0.37; 95% CI 0.25-0.54), but increased injection-site reactions (RR = 1.83; 95% CI 1.46-2.30) within 12 months. No significant differences were observed in other AEs (including cardiovascular AEs) within 12 months. CONCLUSION: Romosozumab treatment resulted in a significant BMD gain, reduced falls and major osteoporotic fractures. It was generally well-tolerated, including the cardiovascular aspects. However, clinicians should consider the occurrence of minor AEs (e.g., injection-site reactions).

GWAS meta-analysis of kidney function traits in Japanese populations.

BACKGROUND: Genetic epidemiological evidence for the kidney function traits in East Asian population including Japanese remain still relatively unclarified. Especially, the number of GWASs for kidney traits reported still remains limited, and the sample size of each independent study is relatively small. Given the genetic variability between ancestries/ethnicities, implementation of GWAS with sufficiently large sample sizes in specific population of Japanese is considered meaningful. METHODS: We conducted the GWAS meta-analyses of kidney traits by leveraging the GWAS summary data of the representative large genome cohort studies with about 200,000 Japanese participants (n = 202,406 for estimated glomerular filtration rate [eGFR] and n = 200,845 for serum creatinine [SCr]). RESULTS: In the present GWAS meta-analysis, we identified 110 loci with 169 variants significantly associated with eGFR (on chromosomes 1-13 and 15-22; p < 5×10-8), whereas we also identified 112 loci with 176 variants significantly associated with SCr (on chromosomes 1-22; p < 5×10-8), of which one locus (more than 1Mb distant from known loci) with one variant (CD36 rs146148222 on chromosome 7) for SCr was considered as the truly novel finding. CONCLUSIONS: The present GWAS meta-analysis of largest genome cohort studies in Japanese provided some original genomic loci associated with kidney function in Japanese, which may contribute to the possible development of personalized prevention of kidney diseases based on genomic information in the near future.

Association between oxidative balance score and inflammatory markers in middle-aged and older Japanese people.

PURPOSE: This study aimed to investigate the association between oxidative balance score (OBS), wherein higher OBSs indicate lower oxidative stress, and high-sensitivity C-reactive protein (hs-CRP), as well as inflammatory scores, in a large cohort of Japanese adults. METHODS: In total, 9703 individuals aged 40-69 years participated in a baseline survey of a population-based cohort study in Saga, Japan (2005-2007). OBSs were calculated from 11 prooxidant and antioxidant lifestyle factors, including dietary intake, physical activity, alcohol consumption, and smoking status. Lifestyle data, including dietary intake, were obtained using a self-administered questionnaire. Adjusted geometric means of serum hs-CRP levels were calculated based on OBS quartiles, and linear trend tests were performed, with adjustments for potential confounders. In addition, an inflammatory cytokine z-score was constructed and assessed alongside individual markers. RESULTS: After adjusting for multiple confounders in both sexes, the results showed a significant inverse association between OBS and serum hs-CRP levels in both men and women. These results remained unaltered when the OBS evaluation excluded powerful prooxidants, serum ferritin, or smoking. There was also an association between OBS and lower inflammatory z-score, indicating reduced overall systemic inflammation. CONCLUSIONS: These findings suggest that a higher OBS, indicating a greater predominance of antioxidants over prooxidant exposure, is associated with lower hs-CRP levels and reduced systemic inflammation, regardless of sex.

Predictive factors of coronavirus disease (COVID-19) vaccination series completion: a one-year longitudinal web-based observational study in Japan.

Introduction: Addresing vaccine hesitancy is considered an important goal in management of the COVID-19 pandemic. We sought to understand what factors influenced people, especially those initially hesitant, to receive two or more vaccine doses within a year of the vaccine's release. Methods: We conducted longitudinal Web-based observational studies of 3,870 individuals. The surveys were conducted at four different time points: January 2021, June 2021, September 2021, and December 2021. In the baseline survey (January 2021), we assessed vaccination intention (i.e., "strongly agree" or "agree" [acceptance], "neutral" [not sure], and "disagree" or "strongly disagree" [hesitance]), and assumptions about coronavirus disease (COVID-19), COVID-19 vaccine, COVID-19-related health preventive behavior, and COVID-19 vaccine reliability. In subsequent surveys (December 2021), we assessed vaccination completion (i.e., ≥2 vaccinations). To investigate the relationship between predictors of COVID-19 vaccination completion, a multivariable logistic regression model was applied. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were calculated while adjusting for gender, age, marital status, presence of children, household income category, and presence of diseases under treatment. In a stratified analysis, predictors were determined based on vaccination intention. Results: Approximately 96, 87, and 72% of those who demonstrated acceptance, were not sure, or hesitated had been vaccinated after 1 year, respectively. Overall, significant factors associated with COVID-19 vaccine compliance included the influence of others close to the index participant (social norms) (AOR, 1.80; 95% CI, 1.56-2.08; p < 0.001), vaccine confidence (AOR, 1.39; 95% CI, 1.18-1.64; p < 0.001) and structural constraints (no time, inconvenient location of medical institutions, and other related factors) (AOR, 0.80; 95% CI, 0.70-0.91; p = 0.001). In the group of individuals classified as hesitant, significant factors associated with COVID-19 vaccine compliance included social norms (AOR, 2.43; 95% CI, 1.83-3.22; p < 0.001), confidence (AOR, 1.44; 95% CI, 1.10-1.88; p = 0.008), and knowledge (AOR, 0.69; 95% CI, 0.53-0.88; p = 0.003). Discussion: We found that dissemination of accurate information about vaccines and a reduction in structural barriers to the extent possible enhanced vaccination rates. Once the need for vaccination becomes widespread, it becomes a social norm, and further improvements in these rates can then be anticipated. Our findings may help enhance vaccine uptake in the future.

Genetic architecture of alcohol consumption identified by a genotype-stratified GWAS and impact on esophageal cancer risk in Japanese people.

An East Asian-specific variant on aldehyde dehydrogenase 2 (ALDH2 rs671, G>A) is the major genetic determinant of alcohol consumption. We performed an rs671 genotype-stratified genome-wide association study meta-analysis of alcohol consumption in 175,672 Japanese individuals to explore gene-gene interactions with rs671 behind drinking behavior. The analysis identified three genome-wide significant loci (GCKR, KLB, and ADH1B) in wild-type homozygotes and six (GCKR, ADH1B, ALDH1B1, ALDH1A1, ALDH2, and GOT2) in heterozygotes, with five showing genome-wide significant interaction with rs671. Genetic correlation analyses revealed ancestry-specific genetic architecture in heterozygotes. Of the discovered loci, four (GCKR, ADH1B, ALDH1A1, and ALDH2) were suggested to interact with rs671 in the risk of esophageal cancer, a representative alcohol-related disease. Our results identify the genotype-specific genetic architecture of alcohol consumption and reveal its potential impact on alcohol-related disease risk.

BMI and Cardiometabolic Traits in Japanese: A Mendelian Randomization Study.

BACKGROUND: Although many observational studies have demonstrated significant relationships between obesity and cardiometabolic traits, the causality of these relationships in East Asians remains to be elucidated. METHODS: We conducted individual-level Mendelian randomization (MR) analyses targeting 14,083 participants in the Japan Multi-Institutional Collaborative Cohort Study and two-sample MR analyses using summary statistics based on genome-wide association study data from 173,430 Japanese. Using 83 body mass index (BMI)-related loci, genetic risk scores (GRS) for BMI were calculated, and the effects of BMI on cardiometabolic traits were examined for individual-level MR analyses using the two-stage least squares estimator method. The ß-coefficients and standard errors for the per-allele association of each single-nucleotide polymorphism as well as all outcomes, or odds ratios with 95% confidence intervals were calculated in the two-sample MR analyses. RESULTS: In individual-level MR analyses, the GRS of BMI was not significantly associated with any cardiometabolic traits. In two-sample MR analyses, higher BMI was associated with increased risks of higher blood pressure, triglycerides, and uric acid, as well as lower high-density-lipoprotein cholesterol and eGFR. The associations of BMI with type 2 diabetes in two-sample MR analyses were inconsistent using different methods, including the directions. CONCLUSION: The results of this study suggest that, even among the Japanese, an East Asian population with low levels of obesity, higher BMI could be causally associated with the development of a variety of cardiometabolic traits. Causality in those associations should be clarified in future studies with larger populations, especially those of BMI with type 2 diabetes.

Association Between the Appendicular Extracellular-to-Intracellular Water Ratio and All-Cause Mortality: A 10-Year Longitudinal Study.

The appendicular extracellular-to-intracellular water ratio (A-E/I) is a potential marker of skeletal muscle quality, reflecting the balance of water distribution between the extracellular and intracellular compartments of the appendicular limb regions. A-E/I has been increasingly used in recent studies; however, its association with adverse outcomes remains unclear. This study investigated the potential association between A-E/I and all-cause mortality. A prospective cohort study of 8 015 middle-aged and older adults (comprised of 4 755 women, aged 45-74 years) residing in a Japanese community was conducted. The baseline assessment was performed between 2010 and 2012, and the follow-up period lasted until July 2022. A-E/I and skeletal muscle mass were measured using segmental bioelectrical impedance spectroscopy. Handgrip strength (HGS) was measured using a Smedley-type dynamometer. Lifestyle, medical history, and physical activity were assessed by questionnaire and accelerometer. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for each quartile (Q) of A-E/I were estimated using the multivariable Cox regression model. During a 10.5-year median follow-up, the mortality rates were 8.9 and 3.6 per 1 000 person-years for men (292 deaths) and women (174 deaths), respectively. A-E/I quartiles were positively associated with all-cause mortality in both sexes (men: Q1, HR: 1.0 [95% CI: reference], Q4, HR: 1.8 [1.1-2.9], ptrend < .05; women, Q4, HR: 2.2 [1.3-3.8], ptrend < .01). This association remained significant after further adjustment for skeletal muscle mass and HGS (ptrend < .05). Our findings suggest that A-E/I serves as an early predictive marker for mortality in middle-aged and older Japanese adults.

Seven-plus hours of daily sedentary time and the subsequent risk of breast cancer: Japan Multi-Institutional Collaborative Cohort Study.

This study aimed to investigate the association between daily sedentary time and the risk of breast cancer (BC) in a large Japanese population. The participants were 36,023 women aged 35-69 years from the Japan Multi-Institutional Collaborative Cohort Study. Cox proportional hazards analysis was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for BC incidence in relation to time spent sedentarily (categorical variables: <7 and ≥7 hours/day [h/d]). Additionally, the associations of BC incidence to the joint effect of sedentary time with each component of physical activity, such as leisure-time metabolic equivalents (METs), frequency of leisure-time physical activity, and daily walking time, were examined. During 315,189 person-years of follow-up, 554 incident cases of BC were identified. When compared to participants who spent <7 h/d sedentary, those who spent ≥7 h/d sedentary have a significantly higher risk of BC (HR, 1.36; 95% CI, 1.07-1.71). The corresponding HRs among participants who spent ≥7 h/d sedentary with more physical activity, such as ≥1 h/d for leisure-time METs, ≥3 days/week of leisure-time physical activity, and ≥1 h/d of daily walking were 1.58 (95% CI, 1.11-2.25), 1.77 (95% CI, 1.20-2.61), and 1.42 (95% CI, 1.10-1.83), respectively, compared with those who spent <7 h/d sedentary. This study found that spending ≥7 h/d of sedentary time is associated with the risk of BC. Neither leisure-time physical activity nor walking had a BC-preventive effect in those with ≥7 h/d of sedentary time.

Associations for progression of cerebral small vessel disease burden in healthy adults: the Kashima scan study.

To investigate the association between vascular risk factors and progression of cerebral small vessel disease (SVD), we conducted a longitudinal study with neurologically healthy cohort composed mostly of middle-aged adults (n = 665, mean age, 57.7 years). Subjects, who had both baseline data of brain health examinations including MRI and follow-up MRI at least 1 year after the baseline MRI, were included this study. The presence of features of SVD, including lacunes, cerebral microbleeds, white matter hyperintensity, and basal ganglia perivascular spaces were summed to obtain "total SVD score" (range, 0-4). Progression of SVD was evaluated among subjects with a total SVD score of ≤ 3 and was defined as a ≥ 1 point increase in that score at follow-up relative to baseline. As the primary analysis, multivariate logistic regression analyses were performed to determine the associations of progression of SVD at baseline. The median follow-up period was 7.3 years and progression of SVD was observed in 154 subjects (23.2%). Even after adjustment with confounders multivariate logistic regression analyses showed that progression of SVD was associated with age (per 10-year increase, odds ratio [OR]: 2.08, 95% confidence interval [CI] 1.62-2.67), hypertension (OR 1.55, 95%CI 1.05-2.29), systolic blood pressure (BP) (per standard deviation [SD] increase, OR 1.27, 95%CI 1.04-1.54), diastolic BP (per SD increase, OR 1.23, 95%CI 1.01-1.50), and mean arterial pressure (per SD increase, OR 1.27, 95%CI 1.04-1.55). Age and high blood pressure appear to play key roles in the progression of cerebral small vessel burden after mid-life.

The Association between Oxidative Balance Score and Urinary Levels of 8-Hydroxydeoxyguanosine among Japanese Adults.

The oxidative balance score (OBS), wherein higher OBSs indicate lower oxidative stress, was designed to assess a composite measure of multiple pro-oxidant and antioxidant effects on an individual's oxidative stress status. This study aimed to evaluate whether OBSs were inversely associated with urinary levels of 8-hydroxydeoxyguanosine (8-OHdG)-an oxidative stress marker-among Japanese adults. This cross-sectional study was based on data obtained during 2010-2012. Overall, 7552 participants from the J-MICC Study Saga who answered a self-administered food frequency questionnaire were recruited for the final analysis. OBSs were calculated from 11 pro-oxidant and antioxidant lifestyle factors, including dietary intake, physical activity, and alcohol and smoking status. Urinary 8-OHdG values were corrected by creatinine level (ng/mg creatinine). Our findings revealed a higher total OBS was significantly associated with lower urinary 8-OHdG/creatinine levels after adjustment for covariates in men and women (p for trend < 0.01 in both sexes). We performed a multiple regression analysis of the association between OBSs and urinary 8-OHdG/creatinine levels stratified by age, body mass index (BMI), and menopausal status and found consistent negative associations in most groups for both sexes. No significant differences in the 60-64 age group for women (standardized ß = -0.09, p = 0.13) or BMI < 18.5 kg/m2 for men (standardized ß = -0.18, p = 0.17) were observed. A higher OBS had a strong inverse association with urinary 8-OHdG/creatinine levels in men and women among Japanese adults. The OBS might be a useful tool for evaluating the roles of oxidative stress-related lifestyle factors, including diet.

Association between green tea and coffee consumption and body iron storage in Japanese men and women: a cross-sectional study from the J-MICC Study Saga.

Purpose: This study examined the association between daily green tea and coffee consumption and body iron stores among Japanese middle-aged and older adults. Methods: This cross-sectional study used data obtained from 2005 to 2007. A total of 10,435 participants were recruited for this study. The participants completed a validated, self-administered food frequency questionnaire on green tea and coffee consumption. A multivariate linear regression analysis was conducted to assess the relationship between green tea and coffee consumption and serum ferritin levels. Additionally, logistic regression analysis was performed to ascertain whether excessive consumption of these beverages was linked to iron deficiency. Results: We observed that higher green tea and coffee consumption was associated with lower ferritin levels in men and postmenopausal women, even after adjusting for covariates (all P for trends <0.05). Among premenopausal women, we found an inverse association between green tea consumption and serum ferritin levels, while no significant association was observed for coffee consumption after adjusting for covariates (green tea, P for trend <0.05; coffee, P for trend = 0.08). Notably, the association between these beverages and iron deficiency was found only in postmenopausal women; the odds ratios (95% confidence intervals) for iron deficiency associated with almost None, <1 cup/day, 1-2 cups/day, and ≥ 3 cups/day were 1.00 (reference), 0.78 (0.26-2.49), 1.29 (0.49-3.39), and 1.59 (0.63-4.04) (P for trend = 0.05), respectively, for green tea and 1.00, 1.32 (0.64-2.73), 1.46 (0.68-3.13), and 2.20 (1.06-4.55) (P for trend <0.01), respectively, for coffee. Conclusion: Higher green tea and coffee consumption was associated with lower serum ferritin levels in men and postmenopausal women. In premenopausal women, consumption of green tea, but not coffee, was associated with lower serum ferritin levels. However, postmenopausal women who ≥3 cups of coffee demonstrated a higher prevalence of iron deficiency compared to those who consumed almost none.

Effectiveness of BNT162b2 vaccine against symptomatic SARS-CoV-2 infection in children aged 5-11 years in Japan during Omicron variant predominate periods.

BACKGROUND: Although the effectiveness of BNT162b2 messenger RNA vaccines against the Omicron variant has been reported in several countries, data are limited in children living in Asian countries. Therefore, this study aimed to estimate the effectiveness of the pediatric primary two-dose monovalent mRNA vaccine series in preventing symptomatic coronavirus disease 2019 (COVID-19) in Japan. METHODS: We conducted a test-negative case-control study (262 test-positive cases and 259 test-negative controls) in patients aged 5-11 years who presented with COVID-19-like symptoms during the Omicron BA.2- and BA.5-predominant periods. Vaccination status, demographic data, underlying medical conditions, lifestyle, personal protective health behaviors, living environment, and PCR test results were obtained using parent-administered questionnaires and clinical records. Vaccine effectiveness (VE) against symptomatic COVID-19 was calculated using a multivariate logistic regression analysis. RESULTS: Of the test-positive cases and test-negative controls, 9.2% (n=24) and 12.7% (n=33) received two vaccine doses, respectively. Having siblings and a BA.5-dominant period were significantly associated with symptomatic COVID-19. After adjusting for age, siblings, study period, and duration after the last vaccination, the overall VE of two-dose vaccination was 50.0% (95% confidence interval [CI], 5%-74%). VE was 72% (95%CI: 24%-89%) within 3 months after the two-dose vaccination, while it decreased to 24% (95%CI: -80% to 68%) after 3 months. CONCLUSION: Two BNT162b messenger RNA vaccine doses provided moderate protection against symptomatic COVID-19 during the Omicron variant period. A time-dependent decrease in VE was noted after the second dose; thus, a booster dose 3 months after the second dose is warranted.

Comparison of self-reported symptoms in COVID-19 patients who had or had not previously received COVID-19 mRNA vaccination.

Although mRNA coronavirus disease 2019 (COVID-19) vaccines have been reported for high effectiveness against symptoms, it remains unclear whether post-vaccination infections are less symptomatic than infections in vaccine-naive individuals. We included patients with COVID-19 diagnosed by polymerase chain reaction tests during Japan's alpha and delta variant epidemics. COVID-19 symptoms at approximately 4 weeks were compared based on COVID-19 vaccination status. In total, 398 cases (372 symptomatic and 26 asymptomatic; 286 unvaccinated, 66 vaccinated with one dose, and 46 with two doses) were analyzed. The most common symptoms were fever (78.4%), fatigue (78.4%), cough (74.4%), loss of taste or smell (62.8%), and headache (59.8%). Post-vaccination infections were significantly less likely to be symptomatic. Possible confounder-adjusted odds ratios of two vaccine doses against fatigue, dry eyes and mouth, insomnia, fever, shortness of breath, unusual muscle pains, and loss of taste or smell were 0.18 (95% confidence interval [CI]: 0.09-0.38), 0.22 (95% CI: 0.08-0.59), 0.33 (95% CI: 0.14-0.80), 0.31 (95% CI: 0.15-0.63), 0.36 (95% CI: 0.16-0.76), 0.40 (95% CI: 0.19-0.82), and 0.44 (95% CI: 0.22-0.87), respectively. Post-vaccination infections after two mRNA COVID-19 vaccine doses show milder and fewer symptoms than infections in unvaccinated patients, highlighting the effectiveness of vaccination.

Dietary Carbohydrate and Fat Intakes and Risk of Mortality in the Japanese Population: the Japan Multi-Institutional Collaborative Cohort Study.

BACKGROUND: Previous cohort studies have yielded contradictory findings regarding the associations of dietary carbohydrate and fat intakes with risks of mortality. OBJECTIVES: We examined long-term associations of carbohydrate and fat intakes with mortality. METHODS: In this cohort study, 34,893 men and 46,440 women aged 35-69 y (mean body mass index of 23.7 and 22.2 kg/m2, respectively) were followed up from the baseline survey (2004-2014) to the end of 2017 or 2018. Intakes of carbohydrate, fat, and total energy were estimated using a food frequency questionnaire. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for all-cause and cause-specific mortality according to percentage of energy intakes of carbohydrate and fat. RESULTS: During a mean 8.9-y follow-up, we identified 2783 deaths (1838 men and 945 women). Compared with men who consumed 50% to <55% of energy from carbohydrate, those who consumed <40% carbohydrate energy experienced a significantly higher risk of all-cause mortality (the multivariable-adjusted HR: 1.59; 95% CI: 1.19-2.12; P-trend = 0.002). Among women with 5 y or longer of follow-up, women with high-carbohydrate intake recorded a higher risk of all-cause mortality; the multivariable-adjusted HR (95% CI) was 1.71 (0.93-3.13) for ≥65% of energy from carbohydrate compared with that for 50% to <55% (P-trend = 0.005). Men with high fat intake had a higher risk of cancer-related mortality; the multivariable-adjusted HR (95% CI) for ≥35% was 1.79 (1.11-2.90) compared with that for 20% to <25%. Fat intake was marginally inversely associated with risk of all-cause and cancer-related mortality in women (P-trend = 0.054 and 0.058, respectively). CONCLUSIONS: An unfavorable association with mortality is observed for low-carbohydrate intake in men and for high-carbohydrate intake in women. High fat intake can be associated with a lower mortality risk in women among Japanese adults with a relatively high-carbohydrate intake.

ALDH2 rs671 variant allele is associated with higher energy intake in middle-aged and elderly Japanese who routinely consume alcohol.

BACKGROUND: According to recent reports, individuals with reduced aldehyde dehydrogenase activity may require more energy for the detoxification of aldehydes. Aldehyde dehydrogenase 2 (ALDH2), an ALDH isozyme, is responsible for detoxifying acetaldehyde, an intermediate metabolite of ethanol. Because the variant allele of the rs671 polymorphism of ALDH2 results in a substantial reduction in enzymatic activity, carriers of this variant allele may have a higher energy demand when consuming alcohol than non-carriers. However, no studies have evaluated this phenomenon to date. METHOD: To test the hypothesis, we statistically examined the interactive effects between the rs671 and ethanol consumption on energy intake using cross-sectional data from a population-based cohort study, the Japan Multi-Institutional Collaborative Cohort Study, which was conducted in Saga city between 2005-2007 (N = 12,068). RESULTS: General linear regression models adjusted for age, sex, ethanol consumption, current smoking status, years of education, dietary restriction, medical history, and physical activity level revealed that energy intake was higher in variant allele carriers than in non-carriers among individuals with alcohol drinking habits, whereas no such correlation was observed among those without drinking habits (≤2 g ethanol/day) (p = 0.03 for interaction between rs671 and ethanol consumption). Energy intake excluding energy from alcoholic beverages, carbohydrate intake, protein intake, and fat intake, showed similar tendencies (p for interaction = 0.01, 0.01, 0.04, and 0.07, respectively). CONCLUSIONS: These findings support the hypothesis that increased energy intake is required for the detoxification of aldehydes in individuals with low ALDH activity. This epidemiological evidence provides a possible scientific basis for understanding aldehyde detoxification mechanisms and suggests a novel phenotype of the ALDH2 rs671 polymorphism.

Correlation Between Work Motivation and Life Events in Female Physicians.

This study interviewed 39 mother-doctors from two university hospitals in Japan to investigate how certain stages in their lives influenced their working motivation. We conceptualized a Motivational Drive Chart to track changes of work motivation from enrollment in medical courses to the present day, recording changes in motivational values, age, and life events. It was found that the average value of motivation increased from the beginning of medical school enrollment until graduation; however, a sudden drop was noted in the age group 25 to 29 due to childcare and work-life conflicts. Motivational values were found to gradually increase in the 30 to 34 age group, owing to professional accomplishments, such as obtaining a specialist license. In Japanese society, social roles have traditionally been divided between men and women. The present study found that Japanese female doctors faced a decrease in work motivation during childrearing stages. The finding suggests that new avenues should be explored to support mother-doctors.

Dose-response relationship between daily step count and prevalence of sarcopenia: A cross-sectional study.

OBJECTIVES: Daily step counts are an easy-to-understand indicator of physical activity; however, there is limited evidence regarding the optimal daily step count to prevent sarcopenia. This study examined the dose-response relationship between daily step count and the prevalence of sarcopenia and explored the optimal dose. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: The study included 7949 community-dwelling middle-aged and older adults (aged 45-74 years) from Japan. MEASUREMENTS: Skeletal muscle mass (SMM) was assessed using bioelectrical impedance spectroscopy, and muscle strength was quantified through handgrip strength (HGS) measurement. Participants who exhibited both low HGS (men: <28 kg, women: <18 kg) and low SMM (lowest quartile in each sex-specific category) were defined as having sarcopenia. Daily step counts were measured for 10 days using a waist-mounted accelerometer. To examine the association between daily step count and sarcopenia, a multivariate logistic regression analysis was performed, adjusting for potential confounding factors such as age, sex, body mass index, smoking status, alcohol consumption, protein intake, and medical history. The odds ratios (ORs) and confidence intervals (CIs) were calculated based on the daily step counts categorized into quartiles (Q1-Q4). Finally, a restricted cubic spline curve was fitted to further investigate the dose-response relationship between daily step count and sarcopenia. RESULTS: The prevalence of sarcopenia in the overall participants was 3.3 % (259/7949 participants), with a mean daily step count of 7292 ± 2966 steps. Expressed in quartiles, the mean daily step counts were 3873 ± 935 steps in Q1, 6025 ± 503 steps in Q2, 7942 ± 624 steps in Q3, and 11,328 ± 1912 steps in Q4. The prevalence of sarcopenia in each quartile of daily step count was 4.7 % (93/1987 participants) in Q1, 3.4 % (68/1987 participants) in Q2, 2.7 % (53/1988 participants) in Q3, and 2.3 % (45/1987 participants) in Q4. The ORs and 95 % CIs adjusted for covariates demonstrated a statistically significant inverse association between daily step count and sarcopenia prevalence (P for trend <0.01), as follows: Q1, reference; Q2, 0.79 (95 % CI: 0.55-1.11); Q3, 0.71 (95 % CI: 0.49-1.03); Q4, 0.61 (95 % CI: 0.41-0.90). The restricted cubic spline curve indicated that the ORs leveled off at approximately 8000 steps per day, and no statistically significant decrease in ORs was observed for daily step counts above this threshold. CONCLUSIONS: The study found a significant inverse association between daily step count and the prevalence of sarcopenia, with the association plateauing when the daily step count exceeded approximately 8000 steps. These findings suggest that 8000 steps per day may be the optimal dose to prevent sarcopenia. Further intervention and longitudinal studies are needed to validate the results.

Sequence analysis of a feline- and porcine-origin G3P[9] rotavirus A strain in a child with acute gastroenteritis in Japan.

We isolated the rare G3P[9] rotavirus strain RVA/Human-wt/JPN/R11-035/2015/G3P[9] from a 2-year-old girl presenting with vomiting and diarrhea who had daily contact with cats in Japan, 2015. Full-genome analysis revealed that the R11-035 strain had an AU-1-like genetic constellation, except for the NSP3 (T) gene: G3-P[9]-I3-R3-C3-M3-A3-N3-T1-E3-H6. Phylogenetic analysis showed that strain R11-035 is closely related to human/feline-like human strains, and only the NSP3 (T1) gene was clustered together with Taiwanese porcine strains. We postulate that the R11-035 strain was directly transmitted from a cat to the patient and acquired its NSP3 gene through intergenotype reassortment with porcine strains before being transmitted to humans.

Association of appendicular extracellular-to-intracellular water ratio with age, muscle strength, and physical activity in 8,018 community-dwelling middle-aged and older adults.

BACKGROUND: The appendicular extracellular-to-intracellular water ratio (Ap ECW/ICW) has recently gained attention as a non-invasive measurable marker of muscle quality. However, there is a lack of basic evidence regarding age-related changes, sex differences, contribution to muscle strength independent of skeletal muscle mass (SMM), and potential improvement through physical activity (PA) in Ap ECW/ICW. METHODS: This cross-sectional study enrolled 8,018 middle-aged and older Japanese individuals (aged 45-75 years). The Ap ECW/ICW and SMM were measured using segmental bioelectrical impedance spectroscopy. Muscle strength was evaluated by measuring the handgrip strength (HGS) with a dynamometer, and the PA level (PAL) was measured with an accelerometer. We performed a linear regression analysis of the associations of the Ap ECW/ICW with age, HGS, and PAL. RESULTS: The Ap ECW/ICW increased by 0.019 for men and 0.014 for women per 5-year increase in age (p < 0.001), and the age-related increase was greater in men than in women (p for interaction <0.001). The Ap ECW/ICW was more strongly associated with the HGS than with the SMM in both men and women (p < 0.001). PAL showed a significant inverse association with the Ap ECW/ICW in both men and women (p < 0.001). CONCLUSIONS: Ap ECW/ICW is higher with age, and it varies by sex. The Ap ECW/ICW may reflect muscle strength more than the SMM, suggesting that the Ap ECW/ICW may be improved by PA. The findings from this study may provide a framework for further Ap ECW/ICW research.