Testosterone affects several organs in the body and is very important for male well-being. Aging men with late-onset hypogonadism (LOH) experience physiologic, psychiatric, and sexual symptoms related to a decline in the serum concentration of testosterone with age. However, it is well-known that the extent of the decline in testosterone concentration does not correlate with the severity of LOH-related symptoms. Therefore, it is difficult to diagnose and treat patients with LOH. In addition, the symptoms, response to testosterone replacement therapy (TRT), and medical insurance coverage differ among ethnicities and countries. The evaluation of testosterone is essential for the diagnosis and treatment of LOH. The effects of testosterone are determined not only by the serum testosterone concentration but also by the androgen receptor sensitivity. A low number of glutamine repeats is indicative of high androgenic activity, and the number shows ethnicity-related differences (fewer in African American than in Caucasian people and more in East Asian people). The diagnosis of LOH is typically made using subjective symptoms and the serum testosterone concentration. The Aging Male Symptoms scale is widely used to evaluate the symptoms. The normal range of total testosterone concentration varies around the world; therefore, clinicians should follow the guidelines of their regional academic society. The principal treatment for LOH is TRT. There are many types of TRT and other treatment strategies are also available. Thus, physicians should treat LOH according to each patient's situation, considering related disorders, such as diabetes, osteoporosis, metabolic syndrome, and depression.
Humans ; Male ; Hypogonadism/drug therapy* ; Testosterone/blood* ; Hormone Replacement Therapy/methods* ; Japan ; Age of Onset ; Aging ; Aged ; Androgens/therapeutic use*

OBJECTIVE: To assess the short-term lag effects of climate and air pollution on hospital admissions for cardiovascular and respiratory diseases, and to develop deep learning-based models for daily hospital admission prediction. METHODS: A multi-city study was conducted in Tokyo's 23 wards, Osaka City, and Nagoya City. Random forest models were employed to assess the synergistic short-term lag effects (lag0, lag3, and lag7) of climate and air pollutants on hospitalization for five cardiovascular diseases (CVDs) and two respiratory diseases (RDs). Furthermore, we developed hybrid deep learning models that integrated an autoencoder (AE) with a Long Short-Term Memory network (AE+LSTM) to predict daily hospital admissions. RESULTS: On the day of exposure (lag0), air pollutants, particularly nitrogen oxides (NO x), exhibited the strongest influence on hospital admissions for CVD and RD, with pronounced effects observed for hypertension (I10-I15), ischemic heart disease (I20), arterial and capillary diseases (I70-I79), and lower respiratory infections (J20-J22 and J40-J47). At longer lags (lag3 and lag7), temperature and precipitation were more influential predictors. The AE+LSTM model outperformed the standard LSTM, improving the prediction accuracy by 32.4% for RD in Osaka and 20.94% for CVD in Nagoya. CONCLUSION Our findings reveal the dynamic, time-varying health risks associated with environmental exposure and demonstrate the utility of deep learnings in predicting short-term hospital admissions. This framework can inform early warning systems, enhance healthcare resource allocation, and support climate-adaptive public health strategies.
Humans ; Hospitalization/statistics & numerical data* ; Cardiovascular Diseases/epidemiology* ; Japan/epidemiology* ; Air Pollutants/analysis* ; Air Pollution/adverse effects* ; Cities/epidemiology* ; Climate ; Respiratory Tract Diseases/epidemiology* ; Deep Learning ; Male

BACKGROUND: As research progresses, there is a growing body of evidence indicating that urinary metallothionein (MT) levels may be elevated in individuals exposed to cadmium (Cd). This study aimed to investigate the potential association between urinary MT levels and causes of mortality among residents of the Kakehashi River Basin who have been exposed to Cd. METHOD: The study involved a total of 1,398 men and 1,731 women were conducted between 1981 and 1982, with follow-up until November 2016. The study employed the Cox proportional-hazards model to examine the association between higher urinary MT concentrations and the risk of all-cause or cause-specific mortality within the population. Furthermore, the Fine and Gray competing risks regression model was used to evaluate the links between specific causes of death. RESULTS: The findings revealed that elevated urinary MT concentrations were linked to increased all-cause mortality and higher mortality rates from renal and urinary tract diseases across all participants. Specifically, in men, higher urinary MT levels were associated with elevated all-cause mortality, while in women, increased concentrations were linked to higher mortality from endocrine, nutritional, and metabolic diseases, as well as cardiovascular diseases. Even after adjusting for competing risks, higher urinary MT concentrations were associated with tumor-related mortality in men and continued to be associated with cardiovascular disease mortality in women. CONCLUSIONS In conclusion, the results suggest that women may face a greater risk of adverse health effects due to prolonged exposure to Cd. Urinary MT levels could potentially serve as a biomarker for mortality from these diseases in populations chronically exposed to Cd.
Humans ; Male ; Female ; Cadmium/urine* ; Japan/epidemiology* ; Metallothionein/metabolism* ; Middle Aged ; Cause of Death ; Adult ; Follow-Up Studies ; Aged ; Environmental Exposure/analysis* ; Proportional Hazards Models

BACKGROUND: A comprehensive understanding of the epidemiology of pediatric out-of-hospital cardiac arrest (OHCA) occurring under school supervision is lacking. We aimed to comprehensively describe the characteristics and outcomes of OHCA among students in elementary schools, junior high schools, high schools, and technical colleges in Japan. METHODS: OHCA data from 2008-2021 were obtained from the SPIRITS study, which provides a nationwide database of OHCAs occurring under school supervision across Japan. We included cases in which resuscitation was attempted by emergency medical service personnel or bystanders. The cases were classified into three groups based on their etiology: cardiac, non-cardiac, and traumatic origin. The primary outcome was one-month survival with favorable neurological outcomes, defined as a Glasgow-Pittsburgh cerebral performance category of 1 or 2. The demographic characteristics, event details, and outcomes were compared across the three groups by using χ² tests for categorical variables and one-way analyses of variance for continuous variables. RESULTS: During the 14-year study period, 602 OHCA cases were confirmed, with 430 (71.4%) classified as cardiac, 91 (15.1%) as non-cardiac, and 81 (13.5%) as traumatic origin. Non-cardiac and traumatic cases were less likely to be witnessed at the time of arrest (46.2% and 42.0%, respectively) than cardiac cases (82.6%; p < 0.001). Initiation of cardiopulmonary resuscitation by bystanders was less common in non-cardiac and traumatic cases (62.6% and 42.0%, respectively) than that in cardiac cases (82.8%; p < 0.001). The delivery of defibrillation using public-access automated external defibrillators was also significantly less frequent in non-cardiac (3.3%) and traumatic cases (6.2%) than that in cardiac cases (59.8%; p < 0.001). Ventricular fibrillation (VF) as the first documented rhythm was observed in 77.9% of cardiac cases but was much less common in non-cardiac (5.5%) and traumatic cases (8.6%; p < 0.001). One-month survival with favorable neurological outcomes was significantly lower in non-cardiac (6.6%) and traumatic cases (0%) than that in cardiac cases (50.2%; p < 0.001). CONCLUSIONS OHCAs of cardiac origin were more frequently associated with VF and had relatively good prognoses. In contrast, OHCAs of non-cardiac and traumatic origins consistently resulted in poor outcomes, highlighting the critical importance of prevention strategies to reduce the occurrence of these incidents.
Out-of-Hospital Cardiac Arrest/etiology* ; Humans ; Japan/epidemiology* ; Male ; Female ; Child ; Students/statistics & numerical data* ; Schools/statistics & numerical data* ; Adolescent ; Cardiopulmonary Resuscitation/statistics & numerical data* ; Emergency Medical Services/statistics & numerical data* ; Epidemiologic Studies

BACKGROUND: Japanese people sleep less compared to other countries around the world. Using a large nationally representative survey in 2019 and 2022, we investigated whether sleep duration and nonrestorative sleep (NRS) among Japanese people have improved or worsened due to the COVID-19 pandemic. METHODS: Data were drawn from the Comprehensive Survey of Living Conditions, a nationwide cross-sectional sample based on self-administered questionnaires. We analyzed 426,510 people in 2019 and 375,578 people in 2022 aged ≥20 living in the community. The generalized estimating equations of the multivariable Poisson regression models were used to estimate adjusted prevalence of NRS by survey year. Potential confounders included gender, age, marital status, family size, housing tenure, equivalent household expenditures, education, employment status, illness under treatment, lifestyle behaviors (i.e., smoking, drinking, dietary, and fitness habits), mental health, and sleep duration. RESULTS: Among the study participants, 35.7% slept less than 6 hours and 20.9% had NRS. Regarding sleep duration, the prevalence of sleep duration of less than 6 hours was significantly lower in 2022 than in 2019 for both men and women. By gender and age, the prevalence of short sleep duration (<6 hours) significantly decreased for both men and women under the age of 49, but increased significantly for men aged ≥50 and women aged ≥75. Regarding NRS, the prevalence of NRS was significantly lower in 2022 than in 2019 regardless of gender and age: Prevalence among men was 21.4% in 2019 and 18.8% in 2022, and prevalence among women was 23.7% in 2019 and 21.2% in 2022. After adjustment for potential confounders, the difference between the 2022 NRS prevalence and the 2019 NRS prevalence was minus 1.64 percent point (pp) (95% confidence interval minus 1.82 pp to minus 1.46 pp, P < 0.001), showing a significant decrease in the 2022 NRS prevalence. A significant improvement of NRS was independent of the prevalence of short sleep duration, age, gender, and employment status. CONCLUSIONS The prevalence of NRS among the general population in Japan was significantly reduced during the COVID-19 pandemic compared to before the COVID-19 pandemic. We need to monitor whether this decline continues or returns to pre-pandemic levels.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; COVID-19/epidemiology* ; Cross-Sectional Studies ; Japan/epidemiology* ; Pandemics ; Prevalence ; SARS-CoV-2 ; Sleep ; Surveys and Questionnaires

BACKGROUND: This cohort study aimed to identify the accumulation patterns of objectively measured ambulatory activity (AA) variables in the middle-aged and older Japanese women and examine the relationship of these derivative patterns with onset of metabolic syndrome (MetS). METHODS: A total of 794 women (mean age: 56.2 years) provided objectively assessed AA data using a uniaxial accelerometer. The number of steps, time accumulated in light-intensity AA (LIAA) and moderate-to-vigorous intensity AA (MVAA) and the ratio of MVAA to total AA (LIAA + MVAA) were calculated. Latent profile analysis was used to identify participant groups based on their distinct AA patterns. Logistic regression models were used to assess the association of groups with the onset of MetS after adjusting for age, sex, education, alcohol habit, smoking habit, energy intake, and the number of MetS components present at baseline. RESULTS: Four distinct groups were identified: Group A had low levels of the AA variable; group B accumulated a certain number or more steps primarily through MVAA; group C accumulated a certain number or more steps primarily through LIAA; and group D had high level of the AA variables. Over the course of the 5-year follow-up period, 61 participants (7.7%) developed MetS. The multivariate-adjusted odds ratio (95% confidence interval) for onset of MetS in groups B, C, and D relative to group A were 0.416 (0.166-1.218), 0.451 (0.223-0.914), and 0.933 (0.365-2.382), respectively. Group C had a significantly lower odds ratio of MetS onset than group A. CONCLUSION AA patterns accumulating a certain number or more steps, regardless of the intensity of AA, may help reduce the risk of MetS compared to inactive AA patterns.
Humans ; Metabolic Syndrome/etiology* ; Female ; Middle Aged ; Japan/epidemiology* ; Aged ; Exercise ; Cohort Studies ; Accelerometry ; Risk Factors ; East Asian People

BACKGROUND: To explore the associations of green tea, coffee, black tea, and oolong tea consumption with mortality from chronic kidney disease (CKD) as the underlying cause among Japanese adults. METHODS: We conducted a prospective cohort study of 110,585 men and women aged 40-79 years at recruitment from 1986 to 1990. Baseline information on the consumption of tea and coffee, lifestyles, and medical histories was obtained via self-administered questionnaires. We used multivariable Cox regression models to estimate sex-specific hazard ratios and 95% CIs of mortality from CKD associated with the consumption of green tea, coffee, black tea, or oolong tea. RESULTS: After a median 19-year follow-up, the hazard ratios of mortality from CKD in women were 0.49 (95% CI, 0.22-1.06) for 1-2 cups of green tea per day, 0.56 (0.31-0.99) for 3-4 cups per day, and 0.55 (0.32-0.93) for ≥5 cups per day, compared with <1 cup per day. No such association was found in men. Coffee, black tea, and oolong tea consumption were not associated with CKD risk in either sex. CONCLUSIONS Daily consumption of green tea was associated with a lower risk of mortality from CKD in women.
Humans ; Tea ; Coffee ; Middle Aged ; Male ; Female ; Japan/epidemiology* ; Renal Insufficiency, Chronic/epidemiology* ; Aged ; Adult ; Prospective Studies ; Risk Factors ; Proportional Hazards Models ; East Asian People

BACKGROUND: Quick accomplishment and responsiveness are behaviors related to time management by perceived control of time, such as a positive feeling of using one's time well. In recent years, positive psychological states have been associated with a lower risk of cardiovascular disease (CVD). Thus, we investigated the associations of quick accomplishment and responsiveness with CVD mortality in a large cohort study. METHODS: The study participants were 75,049 (30,901 men and 44,148 women) aged 40-79 between 1988 and 1990 and followed until the end of 2009. Hazard ratios (HRs) and 95% confidence intervals (CIs) of mortality from CVD according to quick accomplishment, responsiveness, and their combination were calculated after adjustment for potential confounding factors using the Cox proportional hazard model. RESULTS: Quick accomplishment was associated with a lower risk of CVD mortality in women; a similar but marginally significant association was observed in men; the respective multivariable HR (95%CI) was 0.91 (0.83-0.99) and 0.93 (0.86-1.01). The presence of both quick accomplishment and responsiveness was associated with lower risk in men, which was confined to men aged 60-79; the respective multivariable HR (95%CI) was 0.88 (0.78-0.99) and 0.83 (0.72-0.96). CONCLUSIONS Quick accomplishment was associated with a lower risk of CVD mortality. Quick accomplishment and responsiveness combined were inversely associated with CVD mortality risk among older men.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Cardiovascular Diseases/psychology* ; Cohort Studies ; Japan/epidemiology* ; Proportional Hazards Models ; Risk Factors ; East Asian People/psychology*

BACKGROUND: Icaridin and DEET are common insect repellents widely used on human skin and clothing (skin-insect repellents [skin-IR]) to repel common pests, such as mosquitoes and biting flies. Novel analytical methods for urinary skin-IR exposure biomarkers that can be effectively applied in epidemiological studies and provide strong evidence related to risk assessment associated with daily exposure are required. In this study, we aimed to develop a method for analyzing the concentrations of icaridin, DEET, and two DEET metabolites N,N-diethyl-3-(hydroxymethyl) benzamide and 3-(diethylcarbamoyl) benzoic acid in human urine. METHODS: In this analysis, after formic acid-induced acidification of the urine sample, exposure biomarkers were extracted using solid-phase extraction composed of a modified polystyrenedivinylbenzene polymer for reversed phase (hydrophobic) retention. Subsequently, high-performance liquid chromatography-tandem mass spectrometry was performed within 10 min for a separation analysis. The present method was applied to five Japanese adults (aged 20-43 years) who used icaridin or DEET-containing products within a week. RESULTS: Limits of detection were 0.06-0.11 µg/L. Extraction recoveries were 74%-88%. The intraday and interday variations were 1.5-17.5 and 0.9-15.8% relative standard deviation, respectively. All exposure biomarkers were successfully detected in all five adults. Urinary concentrations of exposure biomarkers reached their maximum values within 15 h after starting to use skin-IR. CONCLUSIONS This method was successful in measuring urinary exposure biomarkers of skin-IR, including icaridin and DEET. Moreover, this study presents the first application of biomonitoring of urinary icaridin concentrations after using a commercial product.
Humans ; Solid Phase Extraction/methods* ; Tandem Mass Spectrometry/methods* ; Adult ; Insect Repellents/urine* ; DEET/urine* ; Young Adult ; Male ; Japan ; Female ; Chromatography, Liquid ; Biomarkers/urine* ; Chromatography, High Pressure Liquid ; East Asian People

BACKGROUND: Among the more than 300 mycotoxins that are known to have toxic effects on animals and humans, Fusarium toxins deoxynivalenol (DON), T-2 and HT-2 toxins (T2/HT2), and zearalenone (ZEN) are frequently detected in domestic agricultural products. This study aimed to assess DON, T2/HT2, and ZEN exposure in Japanese adults by measuring urinary mycotoxins, observing their distributions, and making comparisons with data from other countries. METHODS: A total of 201 individuals participated in the study. Twenty-four-hour urine samples were collected from young adults (34 men and 35 women) in the Tokai region (urban area) and spot urine samples were collected from middle-aged and elderly adults (64 men and 68 women) in the Donan area of Hokkaido Prefecture (rural area). Urinary DON, T2/HT2, and ZEN levels were measured using a validated liquid chromatography-tandem mass spectrometry method. RESULTS: For DON, T2/HT2, and ZEN, the detection frequencies above the limit of detection (LOD) level (0.15, 0.13, and 0.01 µg/L, respectively) in all the samples were 53%, 26%, and 71%, respectively. The median concentrations (95^th percentile) of urinary DON, HT2, and ZEN were 0.19 (3.93), CONCLUSIONS This study represents the first comprehensive exposure assessment for DON, T2/HT2, and ZEN in Japanese adults using human biomonitoring methods. These data provide valuable information for a better understanding of mycotoxin exposure in Japan.
Humans ; Zearalenone/urine* ; Japan ; Male ; Female ; Trichothecenes/urine* ; T-2 Toxin/urine* ; Biological Monitoring ; Adult ; Middle Aged ; Aged ; Cross-Sectional Studies ; Young Adult ; Mycotoxins/urine* ; Environmental Exposure/analysis* ; East Asian People