Background: Reproductive history can be conceptualized as a life-course exposure integrating biological and social factors. Although reproductive factors have been associated with stroke risk and cognitive function, their relationships with structural brain changes remain unclear. Evidence from general population–based studies linking reproductive factors to brain volume, an intermediate marker of cognitive decline, is limited. This study examined whether age at menarche, age at menopause, estrogen exposure duration, and parity are associated with brain volume in postmenopausal women.

Methods: This cross-sectional study included 361 postmenopausal women aged ≥55 years from the Ohasama Study in Japan. Reproductive factors were obtained from a 1998 questionnaire were categorized into quartiles, and MRI data from 2009 to 2019 were analyzed with voxel-based morphometry. Associations were assessed using analysis of covariance adjusted for intracranial volume, age, birth cohort, and BMI. Effect sizes were reported as percent change and standardized effect sizes, with the smallest effect size of interest (SESOI) based on one-year age-related brain volume change.

Results: After covariate adjustment, most associations between reproductive factors and brain volume were attenuated. Earlier age at menarche showed a weak trend toward larger temporal lobe volume (β = 0.59 cm³, 95% CI −0.03 to 1.21; p = 0.06), corresponding to a 0.63% change and 0.06 SD, which was comparable to the SESOI (±0.54% or 0.06 SD). Earlier age at menopause was associated with smaller occipital lobe volume (β = −0.52 cm³, 95% CI −1.01 to −0.03; p = 0.04), corresponding to a −1.08% change and 0.10 SD, exceeding the primary SESOI threshold (±0.64% or 0.06 SD), although confidence intervals included effects smaller than the SESOI. No significant associations were found for estrogen exposure or parity.

Conclusion: Reproductive factors were not associated with moderate or large differences in brain volume in postmenopausal women. The slight, region-specific differences observed were comparable in magnitude to short-term age-related changes. These findings suggest that the clinical significance at the individual level is likely limited. However, subtle associations at the population level cannot be entirely excluded.

Background: Heatstroke is a major public health problem during summer, and meteorological conditions, particularly wet bulb globe temperature (WBGT), strongly influence its occurrence. However, even under similar heat conditions, heatstroke risk may vary according to behavioural patterns on weekdays, weekends/holidays, and post-holiday days. This study aimed to examine whether heatstroke-related ambulance transports in Tokyo vary according to day type after adjusting for WBGT.

Methods: We conducted a time-series analysis using daily heatstroke-related ambulance transports in Tokyo, Japan, during the warm season (May–September) from 2015 to 2025. The days were classified as weekday, weekend/holiday, or post-holiday. The WBGT data for seven locations in Tokyo were used, and the highest daily maximum WBGT served as the heat exposure indicator. Modified Poisson regression models were used to estimate risk ratios (RRs) and 95% confidence intervals (CIs) according to day type, adjusting for the WBGT category at lags 0 and 1 and the calendar year. The same models were applied by age group, severity, and place of occurrence. Four sensitivity analyses, including the use of alternative heat exposure indicators and exclusion of the coronavirus disease 2019 period, were conducted.

Results: After adjusting for WBGT and calendar year, the occurrence of heatstroke-related ambulance transports differed according to day type. Overall, ambulance transports tended to be more frequent on post-holiday days than on weekdays (RR, 1.08; 95% CI, 0.97–1.22). Among adults aged ≥65 years, transports were more frequent on post-holiday days (RR, 1.13; 95% CI, 1.00–1.28) and less frequent on weekends/holidays (RR, 0.87; 95% CI, 0.79–0.96). Among individuals aged <18 years, transports were markedly more frequent on weekends/holidays (RR, 1.80; 95% CI, 1.61–2.03). Weekend/holiday increases were also observed in mild cases and in public indoor and outdoor spaces and educational institutions, whereas cases in residences and workplaces were less frequent. Sensitivity analyses yielded similar results.

Conclusions: Heatstroke-related ambulance transports in Tokyo varied according to day type even after adjusting for WBGT, with distinct patterns across age groups, severity categories, and places of occurrence. Weekly behavioural patterns may contribute to heatstroke risk and warrant consideration in preventive strategies.

Background: Long-term birth cohort studies depend on sustained participant engagement. In such studies, children are not only observed over time but also increasingly become participants who experience, interpret, and evaluate their own involvement in research. However, research on continued participation has focused mainly on parental perspectives, with limited attention to children’s own views or to similarities and differences between parents and children. Against the growing recognition that people in medical research should be understood as participants rather than passive subjects, this study examined research participation experiences and retention intentions in both parents and children within a Japanese birth cohort.

Methods: We conducted a questionnaire survey from September to October 2024 within the Japan Environment and Children’s Study (JECS). The primary outcome was retention intention. Factors associated with retention intention were analyzed separately for parents and children using ordinal logistic regression. Parent-child concordance in retention intention was assessed descriptively using weighted Cohen’s kappa.

Results: Among 1,008 eligible parents of fifth-grade children, 485 responded (response rate, 44%). A large majority of parents (92%) and children (79%) reported willingness to continue participation. Parent–child responses showed moderate agreement (κ = 0.46). In separate adjusted ordinal logistic regression models, stronger parental retention intention was associated with lower perceived questionnaire burden (adjusted odds ratio [aOR]: 5.58, 95% confidence interval [CI]: 3.40–9.17), fewer concerns about possible disagreement with their child (aOR: 5.75, 95% CI: 3.51–9.42), and less difficulty scheduling study activities (aOR: 5.80, 95% CI: 3.50–9.63). In children, stronger retention intention was associated with anticipated gifts (aOR: 7.38, 95% CI: 2.93–18.56), talking with friends about the study (aOR: 6.02, 95% CI: 2.25–16.09), and a desire for peer interaction (aOR: 6.72, 95% CI: 3.39–13.29).

Conclusions: Parents and children both showed generally positive retention intentions, but disagreement was not negligible. Their retention intentions were associated with different participation-related experiences, suggesting that long-term birth cohort studies should attend to participants’ perspectives in age-specific ways. Understanding research participation through both parental and child experiences may help inform more participant-centered engagement strategies and support the quality of long-term cohort research.

Background: Accessible and trustworthy health information sources support informed decisions. Longitudinal evidence on how health information sources influence behavioural changes in community-dwelling populations remains limited. Thus, we examined associations between health information sources and behaviour changes in walking time, balanced meal consumption, and smoking cessation.

Methods: Baseline (2021) and follow-up (2023) survey questionnaires were distributed to residents randomly selected from the 18 residential areas. Health information sources were classified into five categories: print media, television (TV) and radio, the Internet, family and friends, and professionals. Desirable health behaviours were defined as walking for ≥60 min/day; consuming ≥2 meals per day comprising staple grains, main dishes, and side items (SMS); and smoking cessation. Meeting these criteria was classified as good; not meeting them as poor. Improvement was defined as poor at baseline and good at follow-up. Maintenance was defined as good at both surveys. Improvement analyses included participants with poor baseline conditions. Maintenance analyses included those with good baseline conditions. Associations were analysed using multilevel modified Poisson regression models, accounting for clustering within residential areas and adjusting for covariates. Risk ratios (RRs) and 95% confidence intervals (95% CIs) were calculated.

Results: Of the 12 119 baseline participants, 6620 (54.6%) completed the follow-up. The most common health information sources were TV and radio (68.5%), the Internet (56.8%), and print media (48.9%). Use of family and friends as information sources was associated with improvement in walking time (RR: 1.19; 95% CI: 1.02–1.39), as was use of professionals (RR: 1.15; 95% CI: 1.03–1.28). Professionals showed a marginal association with sustained walking time (RR: 1.07; 95% CI: 0.99–1.15). TV and radio was associated with improvement in SMS meal consumption (RR: 1.13; 95% CI: 1.02–1.26), while print media was associated with maintenance of SMS meal consumption (RR: 1.05; 95% CI: 1.01–1.08). No sources were related to smoking cessation.

Conclusions: Health information sources showed distinct associations with improved and maintained health behaviours. Interpersonal sources were relevant for improving walking time, while mass media were linked to dietary improvement and maintenance. These findings suggest tailoring health communication strategies to specific health behaviours.

Depression affects more than 280 million people worldwide and remains a major public health challenge, with limited universally effective preventive strategies. Non-pharmacological interventions have gained increasing attention as complements or alternatives to pharmacotherapy. Shinrin-yoku (forest bathing), a Japanese health practice involving immersion in forest environments, has been reported to relieve stress, enhance immune function, and improve mood. This review synthesizes current evidence on the potential preventive effects of forest bathing on depressive symptoms and examines the mechanistic pathways underlying these effects. A structured search of major scientific databases identified studies investigating psychological responses, neuroendocrine and autonomic regulation, immune-inflammatory markers, and related physiological parameters. Across diverse populations, forest bathing consistently reduced negative mood states, improved vigor, and showed beneficial effects on anxiety, depressive symptoms, sleep quality, and stress biomarkers. Mechanistic evidence suggests that forest bathing may modulate the psycho-neuro-endocrino-immune network through improved sleep, reduced stress hormone levels, enhanced parasympathetic activation, and increases in circulating serotonin, oxytocin, and insulin-like growth factor-1, alongside reduced inflammatory markers. While existing findings are promising, most studies involve small samples, short-term interventions, and limited clinical populations. Future large-scale, controlled studies are needed to confirm long-term effects and to clarify whether forest bathing can contribute to prevention or adjunctive management of depressive symptoms.

Background: Tuberculosis (TB) remains a major global health challenge, with delayed diagnosis perpetuating transmission in resource-limited settings. Although the sensitivity of molecular diagnostic methods is high, their dependence on the laboratory infrastructure limits accessibility in many regions. Serological approaches that detect host antibody responses represent a technically simple diagnostic strategy; however, the performance of currently available TB serodiagnostic tests is inconsistent, largely due to suboptimal antigen selection and heterogeneity in host immune responses. Therefore, the identification of conserved antigens naturally recognized during human infection is essential for improving serological diagnostics.

Methods: A cDNA expression library derived from Mycobacterium bovis BCG Tokyo was constructed and screened by colony immunoblotting using pooled sera from patients with active TB. Immunoreactive clones were sequenced and analyzed bioinformatically. The full-length coding sequence of the identified antigen was expressed recombinantly using a cold-shock expression system in Escherichia coli. The recombinant protein was purified and evaluated for immunoreactivity using a Western blot analysis. Serological reactivity was further assessed using a dot-blot assay with individual serum samples from microbiologically confirmed TB patients (n = 40) and healthy controls (n = 40) from the Lao People’s Democratic Republic. Diagnostic performance was evaluated by a receiver operating characteristic (ROC) curve analysis.

Results: Immunoscreening identified a conserved hypothetical protein corresponding to Rv1073 of M. tuberculosis, designated MtbAg1073, for which no antigenicity had been previously reported. The protein was highly conserved among members of the M. tuberculosis complex. Recombinant expression using a cold-shock system produced soluble His-tagged MtbAg1073, which was specifically recognized by sera from TB patients in the Western blot analysis. Dot-blot assays showed significantly higher antibody responses in TB patients than in controls (median intensity: 761.2 vs. 471.9; the Mann–Whitney U test, P = 0.0002). The ROC analysis demonstrated moderate discriminatory performance (AUC = 0.734; 95% CI: 0.624–0.844), with a sensitivity of 70.0% and specificity of 67.5% at the optimal cut-off value.

Conclusions: MtbAg1073 is a conserved and immunoreactive antigen that elicits detectable antibody responses in active TB. These findings provide preliminary evidence of its immunoreactivity and warrant further investigation into its potential utility in serological approaches.

Background: Environmental endocrine disruptors (EEDs), endocrine-interfering pollutants, attract attention for potentially affecting heart diseases via epigenetics. Nonylphenol (NP), a classical representative of endocrine-disrupting chemicals, has previously been demonstrated by our research group to induce myocardial fibrosis in rats. LncRNA, a gene regulator, mediates EED-induced heart cell damage and fibrosis.

Objective: This study aimed to investigate the role of long noncoding RNA OIP5 antisense RNA 1 (lncRNA OIP5-AS1) knockdown in NP-induced myocardial fibrosis.

Methods: Small interfering RNA (siRNA) transfection was used to interfere with the expression of lncRNA OIP5-AS1 in H9C2 cells. Lactate dehydrogenase (LDH), cell Counting Kit-8 (CCK-8), transwell, quantitative real time polymerase chain reaction (qRT-PCR), and Western blot assays were employed to detect cell membrane integrity, proliferation, migration ability, and the expression of fibrosis-related genes/proteins in H9C2 cells. This process was also validated in Sprague Dawley (SD) rats.

Results: The expression of fibrosis-related factor mRNA and proteins in H9C2 cells increased, and the expression of lncRNA OIP5-AS1 was significantly upregulated after 24 h of exposure to 70 µmol/L NP. The knockdown of lncRNA OIP5-AS1 did not show differential changes in LDH activity across treatment groups. However, the knockdown of lncRNA OIP5-AS1 significantly attenuated NP-induced proliferation and migration abilities of H9C2 cells and inhibited the increase in the expression of fibrosis-related factor mRNA/proteins caused by NP. This suggested that the interference with lncRNA OIP5-AS1 expression inhibited the NP-induced myocardial fibrosis in H9C2 cells. In vivo results suggested that NP exposure and isoproterenol hydrochloride groups in rats showed accumulation of myocardial collagen fibers in the interstitial space, increased distribution and content of collagen fibers, and elevated expression of fibrosis-related proteins. The distribution range, content of collagen fibers, and expression of fibrosis-related proteins significantly reduced in rats with lncRNA OIP5-AS1 knockdown exposed to NP compared with those in the NP group.

Conclusions: The expression of lncRNA OIP5-AS1 was upregulated in NP-treated H9C2 cells, rat hearts, and myocardial fibrosis model rats. Knockdown of lncRNA OIP5-AS1 was associated with attenuated NP-induced myocardial fibrosis and reduced collagen deposition.

Background: Nitrogen dioxide (NO₂) and ozone (O₃) exposure is associated with alterations in liver function, but epidemiological evidence in pregnant women remains limited, especially regarding the combined effects. This study aimed to investigate the associations of exposure to NO₂ and O₃ with maternal liver function and their roles in the combined effect of air pollutant mixture.

Methods: A birth cohort study with 11,909 pregnant women was conducted in Shenzhen, China. Exposure concentration of air pollutants during the first trimester were assessed based on the residential addresses of the pregnant women. Generalized additive model was used to analyze the association of NO₂ and O₃ exposure with maternal liver function. Furthermore, quantile G-computation model was used to investigate the combined effects of air pollutant mixture and the contribution of each pollutant.

Results: Each 10 µg/m³ increase in first-trimester NO₂ exposure was associated with elevated alanine aminotransferase (ALT) and total bilirubin (TBIL) in both the second trimester (ALT: 15.45%, 95% CI: 10.12%, 21.04%; TBIL: 6.69%, 95% CI: 3.75%, 9.72%) and third trimester (ALT: 3.89%, 95% CI: 0.32%, 7.59%; TBIL: 9.27%, 95% CI: 6.52%, 12.10%). For O₃, first-trimester exposure showed a positive association with second-trimester TBIL (2.03%, 95% CI: 1.25%, 2.81%), but was inversely associated with third-trimester ALT (−2.73%, 95% CI: −3.86%, −1.58%) and TBIL (−0.81%, 95% CI: −1.45%, −0.17%). These associations remained significant in the two-pollutant model. The Qgcomp analysis revealed that a one-quartile increase in the air pollutant mixture was associated with a 2.05% (95% CI: 0.56%, 3.56%) increase in third-trimester TBIL, with NO₂ accounting for 55.6% of the positive weight in the model.

Conclusions: First-trimester NO₂ exposure was associated with elevated maternal liver function biomarkers in both the second and third trimesters, while O₃ showed trimester-dependent associations. Exposure to air pollutant mixture was associated with increased third-trimester TBIL, and NO₂ may be the predominant relative contributor. These findings highlight the need for further studies and public health attention to air pollution exposure during pregnancy to protect maternal and fetal health.

Background: Gender disparities in the intention to leave research careers after marriage have not been investigated. This study aimed to clarify the gender-specific associations of marital status and nurturing children with the intention to leave research careers among medical researchers.

Methods: A cross-sectional study was conducted from December 2022 to January 2023. The study was based on a web-based survey targeting medical researchers affiliated with 141 Japanese academic societies. Participants who disagreed with continuing their research careers were classified as intending to leave. Multivariable-adjusted logistic regression analysis was used to evaluate the gender-specific association of marital status and having children with the intention to leave research careers.

Results: Among 3,009 participants, 812 (27.0%) were women, and 342 (11.4%) expressed an intention to leave. A total of 2,481 participants (82.5%) were married, and 2,267 (75.3%) had children. Marital status was associated with intention to leave research careers in opposite directions for men and women, with significant interactions on both multiplicative (P = 0.015) and additive (P = 0.001) scales. Specifically, married men had a significantly lower intention to leave compared with unmarried men (adjusted odds ratio [aOR] 0.63, 95% confidence interval [CI]: 0.40–0.97). In contrast, among women, marriage was associated with a higher intention to leave compared with being unmarried (aOR 1.41, 95% CI: 0.86–2.32), although this increase was not significant. In post hoc subgroup analyses by medical license status, the gender-specific association between marital status and intention to leave research careers was more evident among medical doctors (MDs) than non-MDs, among whom the proportion reporting intention to leave was lower (4% to 6% across groups). However, estimates among non-MD researchers were imprecise due to the small number of events. Similar gender disparities were observed for having children, although the interaction did not reach statistical significance (P for additive interaction = 0.083).

Conclusions: The present results suggest that marital status showed opposite associations with intention to leave research careers between men and women, a pattern primarily observed among MD researchers. Our finding highlights the need to consider gender difference when developing strategies to support retention of medical researchers.

Background: Although marital status is a key social determinant of health, its prognostic relevance in cardiopulmonary exercise testing (CPX) cohorts remains unclear. We aimed to evaluate the association between marital status and mortality risk in patients with cardiac disease (CD) who underwent CPX.

Methods: This retrospective, single-center observational study involved consecutive patients with CD who underwent post-discharge CPX between 2008 and 2020. Participants (mean age: 69 years; 73% male) were categorized as either unmarried (never married, divorced, or widowed) or married. The primary outcome was all-cause mortality, and the secondary outcome was cardiovascular mortality. We used Cox proportional hazards models to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Model 1 was adjusted for age and sex to estimate the overall association between marital status and outcomes. Model 2 was adjusted for Model 1 covariates and peak VO₂ to account for objectively measured exercise capacity.

Results: Of 4,681 patients analyzed, 1,117 were unmarried and 3,564 were married. In Model 1, being married was associated with a lower risk of all-cause mortality (aHR: 0.75, 95% CI: 0.62–0.91, P < 0.001). This association persisted after adjusting for peak VO₂ in Model 2 (aHR: 0.79, 95% CI: 0.65–0.96, P = 0.002). For cardiovascular mortality, the estimates were consistent in direction (Model 1; aHR: 0.64, 95% CI: 0.44–0.93, P = 0.019, Model 2; aHR: 0.69, 95% CI: 0.47–1.02, P = 0.061).

Conclusions: In a large CPX cohort of patients with CD, married status was associated with a lower risk of all-cause mortality. The association was attenuated but remained after adjustment for peak VO₂, suggesting that differences in exercise capacity may contribute but do not fully account for the observed association. Marital status should be interpreted as a social marker rather than a causal or interventional exposure, and future studies should clarify modifiable factors related to prognosis.

Background: Evidence regarding the association between ambient polycyclic aromatic hydrocarbon (PAH) mixtures and non-neoplastic gastrointestinal diseases in general populations remains limited. This study examined whether provincial ambient particulate-phase PAH burden was associated with prevalent gastrointestinal disease among middle-aged and older adults in China.

Methods: Provincial annual mean concentrations of particulate-phase PAHs for 2015 were compiled from published monitoring studies across 12 Chinese provinces and linked to participants in the 2015 wave of the China Health and Retirement Longitudinal Study. Gastrointestinal disease was defined as a self-reported physician diagnosis and/or current treatment, excluding tumors and cancer. Using multivariable logistic regression, we estimated odds ratios and 95% confidence intervals for prevalent gastrointestinal disease per doubling (log2) of total PAHs and of 17 individual PAHs, adjusting for demographic, socioeconomic, and health-related covariates. The Benjamini–Hochberg procedure controlled the false discovery rate. Likelihood ratio tests for interaction were used to assess effect modification.

Results: Of 3,671 adults aged 45 years or older, 1,056 (28.8%) reported a gastrointestinal disease. In fully adjusted models, each doubling of total PAH concentration was associated with increased odds of gastrointestinal disease (odds ratio 1.07, 95% confidence interval 1.02–1.12; false discovery rate–adjusted q = 0.014). Following multiple-comparison correction, naphthalene, fluorene, phenanthrene, and pyrene each demonstrated consistent positive associations. The association for total PAHs was more pronounced among non-drinkers (odds ratio 1.43, 95% confidence interval 1.19–1.71; P for interaction = 0.015) and rural residents (odds ratio 1.37, 95% confidence interval 1.15–1.65; P for interaction = 0.035).

Conclusions: Higher provincial ambient particulate-phase PAH burden was associated with a greater prevalence of self-reported non-neoplastic gastrointestinal disease among middle-aged and older Chinese adults, with potential heterogeneity by residence and alcohol consumption. Given the cross-sectional design and province-level exposure assignment, longitudinal studies with individual-level exposure assessment and validated outcomes are needed.

Background: New tobacco products, including heated tobacco products and electronic cigarettes, are rapidly increasing in popularity among younger populations worldwide, particularly in Japan. Thus, clarifying the effects of both active and passive smoking of new tobacco products during pregnancy is an urgent public health concern. We focused on nausea and vomiting in pregnancy (NVP) which is traditionally and epidemiologically considered an indicator of healthy pregnancy progression. In this study, we classified maternal and paternal smoking status focussing on new tobacco product use and investigated its association with the absence of NVP.

Methods: This cross-sectional study used control data from a case–control study designed to explore modifiable factors for anorectal malformations. The questionnaire survey was conducted within seven Japanese regions between December 2019 and March 2023, enrolling a total of 1,522 postpartum women. The study included 1,450 postpartum women who delivered singleton babies and provided complete information. The main outcome was the absence of NVP. The exposure was the smoking status of mothers and their partners, classified into four categories: dual users (combustible cigarettes and new tobacco products), new tobacco product-only users, combustible cigarette-only users, and non-smokers (reference). Logistic regression analysis was performed to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the absence of NVP.

Results: Based on maternal smoking status, the absence of NVP was reported in 27.1% of dual users, 25.0% of new tobacco product–only users, 18.0% of combustible cigarette–only users, and 15.2% of non-smokers. Maternal dual use was associated with an increased OR of the absence of NVP (adjusted OR = 2.07, 95% CI: 1.02–4.22). After restricting to non-smoking mothers, the adjusted OR for paternal combustible cigarette smoking was 2.62 (95% CI: 1.25–5.50).

Conclusion: Our main finding was the positive association between maternal dual use of new tobacco products and combustible cigarettes during pregnancy and the absence of NVP. This suggests that smoking cessation guidance during pregnancy, including new tobacco products, is particularly warranted.

Trial registration: Not applicable.

Background: Thyroid hormones support endothelial repair, whereas bedtime snacking is linked to a higher risk of chronic kidney disease (CKD). Since endothelial dysfunction is a core feature of CKD, bedtime snacking could potentially contribute to subclinical hypothyroidism (SCH) by elevating the demand for endothelial repair. This study aimed to explore the association between bedtime snacking and SCH.

Method: In this cross-sectional study, 1,478 Japanese individuals aged 40–69 years with normal thyroid function were enrolled; normal thyroid function was defined as free triiodothyronine (T3) and free thyroxine (T4) levels within the reference ranges and the absence of thyroid-related medication use. Individuals with elevated serum concentrations of TSH (>4.01 µIU/mL) were defined as having SCH. Bedtime snacking was determined in the basis of participants’ affirmation to the question “Do you consume a night meal or snack after dinner, within two hours of bedtime, three or more times per week? (Yes, No)”.

Results: In the study population, 263 individuals reported a bedtime snacking habit, whereas SCH was identified in 81 individuals. A statistically significant association was found between bedtime snacking and SCH. The sex- and age-adjusted odds ratios (OR) and 95% confidence intervals (CI) were 1.77 (1.05, 2.99). This association remained significant after additional adjustment for skipping breakfast and late dinner; 1.83 (1.07, 3.11), and further adjustment for free T4, atherosclerosis, hypertension, diabetes, CKD, and thyroid cysts; 1.93 (1.11, 3.35), respectively.

Conclusion: Bedtime snacking is positively associated with SCH, potentially due to an increased physiological demand for endothelial repair. This finding is not only an efficient tool for diagnosing the early stages of endothelial and thyroid dysfunction, but also for clarifying the mechanism underlying the regulation of thyroid hormones related to endothelial health.

Background: Competing endogenous RNAs (ceRNAs) represent a novel mechanism involving interactions among different RNAs, playing a crucial role in the gene regulatory networks throughout the life cycle. CeRNAs are implicated in cardiovascular diseases (CVDs) caused by environmental endocrine disruptors (EDCs); however, existing studies are not yet systematic, and the mechanisms underlying their effects remain unclear.

Objective: This study aimed to systematically elucidate the role of ceRNAs in EDC-induced CVDs and provide valuable insights regarding disease mechanisms and developing new therapeutic strategies.

Methods: Comprehensive searches for research related to EDC-induced cardiovascular diseases were conducted across PubMed, Web of Science, and ScienceDirect databases. Eligible studies were screened, and those containing information on the regulatory mechanisms of ceRNAs were extracted and analyzed.

Results: Notably, ceRNA-mediated effects of EDC exposure on CVDs mainly occurred through four pathways. First, upon exposure to EDCs, micro RNAs, messenger RNAs (mRNAs), long-chain non-coding RNAs, circular RNAs are differentially regulated, activating signaling pathways such as nuclear factor erythroid 2-related factor 2 and p38 mitogen-activated protein kinase/nuclear factor-κB, which lead to atherosclerosis. Second, EDC exposure alters mRNAs and proteins involved in ceRNA networks, activating the PTEN-induced kinase 1/Parkin and transforming growth factor-β1/LIM domain kinase 1 signaling pathways, leading to cardiomyopathy. Third, EDCs increase ceRNA-related mRNA levels, thereby raising the risk of CVDs. Lastly, ceRNAs participate in EDC exposure to upregulate nitric oxide or reactive oxygen species, ultimately causing vascular diseases.

Conclusion: Altogether, the findings of this study show that ceRNAs hold significant potential for identifying target genes and signaling pathways associated with CVDs, which may facilitate deeper studies into CVD management.

Background: This letter highlights the importance of clinical epidemiology in COVID-19 prevention and control, based on experiences at a core hospital in northern Okinawa, Japan, and relevant literature.

Methods: Using data from 5,097 COVID-19 patients, we conducted: (1) a descriptive cross-sectional study analyzing cases by person, time, and place; (2) an analytical cross-sectional study linking health checkup data to identify factors associated with severity (published in Environmental Health and Preventive Medicine); and (3) a cohort study of healthcare workers exploring determinants of post-vaccination antibody titers (published in Journal of Clinical Virology Plus).

Results: The descriptive study showed cases rose from 70 in 2020 to 891 in 2021 and 3,995 in 2022, before declining to 141 in 2023. In the analytical cross-sectional study (n = 1,353), protective factors against severity included vaccination (odds ratio [OR] [2 doses vs. 0 or one doses]: 0.223, 95% confidence interval [CI] 0.114–0.436; OR [≥3 doses vs. 0 or one doses]: 0.090, 95% CI 0.035–0.229) and regular exercise (OR [“yes” vs. “no”]: 0.458, 95% CI 0.242–0.866). In the cohort study (n = 354), lower antibody titers (lowest quartile) were more likely among older adults (hazard ratio [HR] 5.82 for 40s vs. 20s, 95% CI 2.05–16.51; HR 9.96 for 60s vs. 20s, 95% CI 3.07–32.34) and drinking habits (HR 2.26 for “daily” vs. “never”, 95% CI 1.17–4.34).

Conclusion: These findings, supported by related literature, demonstrate that clinical epidemiology played vital roles in monitoring infection trends, evaluating diagnostic and preventive measures, establishing treatment strategies, optimizing healthcare resources, and guiding policy. Its continued application will be essential for preparedness against future emerging infectious diseases.

Background: Olfactory stimulation with hinoki cypress essential oil reportedly reduces stress hormones and enhances parasympathetic activity, which may in turn increase salivary secretion and facilitate swallowing. However, its effects on swallowing in older adults with dysphagia remain unclear.

Methods: In this placebo-controlled, single-blind, randomized crossover study, older adults with dysphagia (Food Intake Level Scale ≤9) underwent 5-minute olfactory stimulation with hinoki cypress essential oil or rice oil (placebo) in two sessions one week apart. Repetitive saliva swallowing test (RSST), 3 mL modified water swallowing test (MWST), 30 mL water swallowing test (WST), saliva secretion for 5 minutes, blood pressure, and heart rate were measured before and after each stimulation. Changes from pre- to post-stimulation were compared within each condition and between conditions using Wilcoxon’s signed-rank test.

Results: Thirty-four participants (47% women; 80 ± 10 years) were included. Hinoki cypress essential oil significantly improved RSST (median difference 0.5, 95% CI 0.0–1.0; p = 0.004), MWST (0.5, 95% CI 0.0–1.0; p = 0.003), and saliva secretion (1.0 mL, 95% CI 0.5–2.0; p = 0.002), whereas placebo produced no significant change (all p > 0.05). Improvements in swallowing function were greater with hinoki than with placebo. The increase in saliva secretion following hinoki stimulation was not associated with changes in RSST or MWST scores.

Conclusions: Brief olfactory stimulation with hinoki cypress essential oil improved swallowing function and increased saliva secretion in older adults with dysphagia compared with placebo in a randomized crossover design. Hinoki cypress essential oil inhalation may represent a simple, noninvasive adjunctive strategy for dysphagia management, warranting confirmation in larger and longer trials.

Trial registration: This study was registered in the UMIN Clinical Trials Registry (UMIN-CTR) under registration number UMIN000053271.

Background: Per- and polyfluoroalkyl substances (PFAS) have raised significant health concerns. In 2019, drinking water source was changed due to PFAS contamination in the Tama region, Tokyo, Japan. This study aims to determine the PFAS exposure levels after reduction in drinking water contamination, and to estimate the half-lives of linear isomers of perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), and perfluorooctanoic acid (PFOA) in serum samples from residents.

Methods: 17 participants in 2020 and 2023 from Tama region, Tokyo, Japan (all females, age 53–83 years) were examined. PFAS concentrations in serum in 2023 were measured using gas chromatography-mass spectrometry. Biological half-lives were estimated using first-order kinetics model.

Results: The investigated population was exposed to six PFAS at levels associated with potential health risks, with 95% of them having total PFAS concentrations exceeding 20 ng/mL in 2023. Serum PFOS, PFHxS and PFOA levels decreased from 2000 to 2023 (p < 0.05 by paired t-test). The estimated half-lives for PFOS, PFHxS, and PFOA were 3.9 years (95% CI: 3.4–4.6), 5.7 years (95% CI: 4.6–7.5), and 8.0 years (95% CI: 6.0–10.0), respectively. After subtraction of background values in Japan, the estimated half-lives were 2.7 years (95% CI: 2.3–3.4) for PFOS, 5.6 years (95% CI: 4.5–7.4) for PFHxS, and 5.1 years (95% CI: 4.1–6.8) for PFOA.

Conclusions: This study demonstrates participants had still higher serum PFAS levels and these PFAS elimination half-lives in the investigated Japanese population are at years order.

Background: Optimizing nutrient intake is crucial for the health and development of preschool children. While previous studies assessed the risks and benefits of selenium (Se) from fish and seafood, few have examined its intake from common foods and its association with children’s growth.

Objective: In this study, we evaluated optimal foods for achieving a dietary Se surplus and the implications for the growth performance of preschool children.

Methods: Mercury (Hg) and Se concentrations were analyzed in 108 commercially available foods to conduct a dietary risk-benefit assessment of Se intake. Hg exposure was evaluated using hair samples from 349 preschool children enrolled between August 2017 and July 2022. Information on food consumption frequencies and nutrient compositions was obtained through dietary surveys.

Results: Overall, 42.4% of children had hair Hg levels above the US Environmental Protection Agency’s reference dose of 1 µg/g, showing that Hg exposure among preschool children in Taiwan remains a significant issue. The risk-benefit assessment revealed that eggs and fish are superior sources of Se compared to other animal- and plant-based foods. Although marine fish contained higher Hg concentrations than eggs, their relatively high Se and ω-3 polyunsaturated fatty acid (PUFA) contents supported a favorable nutritional profile when consumed in moderation. The minor negative health benefit value of Se (HBV_Se) observed for fruit does not pose a health concern, as it is offset by other Se-rich foods in the diet. The cumulative HBV_Se across food groups indicated that the children’s overall dietary Se intake was positive and nutritionally advantageous. Dietary Se, mainly from fish and eggs, was positively associated with weight and height development, whereas excessive fruit consumption may slightly reduce Se intake and adversely affect growth.

Conclusions: Moderate consumption of fish and eggs should be encouraged to support optimal growth and neurodevelopment. Overall, dietary patterns of Taiwanese preschool children provide beneficial levels of Se and ω-3 fatty acids while maintaining low Hg-related risks, emphasizing the need for continued monitoring of Hg levels in locally consumed foods to ensure dietary safety.

Background: The creatinine (Cre) concentration in urine is used as an adjustment factor in chemical exposure and nutritional intake assessments. Because Cre excretion varies by sex, age, race, and anthropometric measurements such as height and weight, developing a method suitable for estimating one-day Cre excretion is necessary. Accordingly, this study aimed to develop a predictive equation for individual one-day Cre excretion in Japanese school children.

Methods: Urine samples were collected from 113 boys and 91 girls (aged 6–12 years) from the Aichi Prefecture, Japan, who were free from diseases affecting the renal, muscle, or nervous systems. Urinary concentrations and one-day excreted amounts of Cre were measured and compared with the values obtained using previously reported equations or a fixed value, totaling 11 methods. Subsequently, we developed a new equation using machine learning and multiple regression analyses. Additionally, the estimated one-day sodium excretion value calculated using this equation was compared with the measured value.

Results: Among the 11 methods to predict Cre excretion, 7 overestimated—5 of which showed a positive trend bias with larger differences at higher average concentrations—and 3 underestimated—2 of which showed a negative trend bias with larger differences at lower average concentrations. A new machine learning model using sex, age, and body surface area (calculated from height and weight) yielded the most accurate prediction. Multiple regression analysis, which demonstrated the most accurate prediction, used sex, age, and body surface area as independent variables with or without the first void Cre concentration divided by urination duration from the previous night’s urination to the first void. Moreover, the difference in one-day sodium excretion from first-void urine predicted using our newly developed Cre equation increased as the measured values increased.

Conclusions: Our study suggests that the estimation of one-day Cre excretion based on sex, age, and body surface area is most appropriate for Japanese schoolchildren, particularly in assessing their chemical exposure and dietary nutrient intake.

Trial registration: Trial registration is not applicable as this observational study did not involve any intervention or randomization requiring registration in a clinical trials registry.

Background: Difficulty in chewing has been shown to be associated with increased mortality, geriatric syndromes, and poor activities of daily living, indicating the need for intervention. Chewing difficulties are related to tooth loss, periodontitis, dry mouth, and a number of oral health conditions. Diabetes mellitus (DM) is one of the major causes of global burden of diseases, and has been associated with poor oral health. Prospective association between oral health status and the development of diabetes has also been reported. However, relationship between glycemic control and self-reported chewing difficulty remains less explored in working-age populations. The objective of this study is to cross-sectionally explore the association between fasting blood glucose (FBG) and self-reported chewing difficulty in adults working in a Japanese worksite.

Methods: Participants from the Aichi Workers’ Cohort Study who responded to the 2018 survey were included. Participants were categorized into five FBG groups (<100, 100–109, 110–125, 126–159, and ≥160 mg/dl). Multivariable odds ratios (ORs) and 95% confidence intervals (CIs) for chewing difficulty were estimated using logistic regression adjusted for age, sex, body mass index, smoking and alcohol consumption status, number of teeth, presence of periodontal disease and the number of anti-diabetic medication classes.

Results: A total of 164 participants (4.2%) reported difficulty with chewing, the prevalence of which tended to increase with increasing FBG level. FBG ≥160 mg/dl was significantly and strongly associated with difficulty with chewing in the final multivariable model (multivariable OR 3.84 [95% CI 1.13–13.0]).

Conclusions: A relationship between higher FBG levels and difficulty with chewing was observed, independent of potential confounding factors. However, prospective or interventional studies are needed to determine causality.