Search Results (765)

The significance of less abundant genera within the gut microbiota, such as Parabacteroides, remains largely unexplored. Despite its low levels, Parabacteroides is highly conserved and potentially beneficial across populations. This trial aimed to evaluate whether a four-week intake of glucolacto-oligosaccharides (GLO), previously reported as an enhancer of Parabacteroides, improves defecation frequency as the primary outcome. It also assessed holistic gut health and underlying microbiota-based mechanisms. In this randomized, double-blind, placebo-controlled trial, 50 healthy Japanese participants with a defecation frequency of five or fewer times per week were enrolled. The mean (±SE) weekly defecation frequency in the GLO group was 3.2 ± 0.2 at baseline, increasing to 5.8 ± 0.6 at week 4, whereas that in the placebo group was 3.4 ± 0.3 at baseline, increasing to 4.4 ± 0.3 at week 4. The time-dependent weekly defecation frequency was significantly higher in the GLO group than in the placebo group (p = 0.029). Changes in the relative abundance of the genus Parabacteroides significantly increased in the GLO group compared with in the placebo group. Changes in fecal bile acid composition were also confirmed in the GLO group compared with the placebo group, which was thought to be due to the unique features of Parabacteroides. Furthermore, changes in alpha diversity indices were significantly higher in the GLO group than in the placebo group (Simpson, p = 0.041; Pielou, p = 0.022). Additional analysis demonstrated that the increase in alpha diversity in the GLO group was significantly correlated with the increase in the relative abundance of Parabacteroides (p = 0.006), which tended to be associated with decreases in serum gamma-glutamyltransferase (p = 0.089) and serum triglyceride (p = 0.075) levels. These data suggest that GLO intake improved defecation status, selectively increased Parabacteroides, and harmonized the gut environment. Full article

Early initiation of remdesivir (RDV) is recommended to improve COVID-19 outcomes, but real-world studies describing patterns of RDV use and related outcomes among Japanese COVID-19 patients at high-risk of severe outcomes or death are limited. This claims-based cohort study included 60,165 high-risk patients hospitalized with COVID-19 between October 2021 and June 2023 using the DeSC Healthcare claims database. Patients were categorized into early-RDV (within 2 days of hospital admission), late-RDV (between day 3 and day 7), and no-RDV groups based on RDV initiation timing. Descriptive analyses were performed according to RDV groups. Of the study patients, ≥85% were very elderly (≥75 years). Approximately 39% of patients received early RDV, 2% received late RDV, and 59% received no RDV. By day 28, the proportion of alive discharge for early-, late-, and no-RDV groups was 74.9%, 63.1%, and 71.8%, respectively. The mortality for early-, late-, and no-RDV groups was 7.7%, 8.8%, and 8.4%, respectively. Future hypothesis-driven studies with an appropriate adjustment for confounders are needed to formally evaluate the impact of RDV initiation timing on clinical outcomes in this high-risk, predominantly late-elderly population in Japan. Full article

Background/Objectives: Japan, the world’s first super-aged society, has confronted rapid population aging and increasing healthcare demands earlier than any other country. In this context, dysphagia rehabilitation has become a critical issue affecting quality of life and survival. With nearly 30% of the population aged ≥65 years, Japan has developed a distinctive dysphagia rehabilitation model characterized by interprofessional collaboration and dental involvement. This narrative review describes its historical evolution and structural characteristics. Methods: This narrative review employed a structured literature search of PubMed and Ichushi-Web, supplemented by manual searches of policy documents and professional guidelines. Publications from 1980 to January 2026 were included if they addressed dysphagia rehabilitation systems or dental involvement in Japan. Both English- and Japanese-language sources were analyzed using thematic synthesis. Results: Japan’s dysphagia rehabilitation model evolved alongside population aging and is embedded within the universal health insurance and long-term care insurance systems. A prominent characteristic is the sustained involvement of dental professionals, who contributed to the foundational development of the field and remain actively involved across care settings, particularly within community- and home-based care. The system is further supported by certification frameworks, a triadic model integrating rehabilitation, nutrition, and oral health, and institutionalized interprofessional education. Conclusions: Previous studies have examined specific aspects of dysphagia care in Japan, but few have examined the overall structure of the system. This review maps the fundamental structure of Japan’s dysphagia rehabilitation model within its historical and policy context, offering insights relevant to dysphagia care in other aging societies. Full article

Background/Purpose: Rectal neuroendocrine tumors (NETs) with distant metastases are uncommon, and evidence supporting the effectiveness of peptide receptor radionuclide therapy (PRRT) in this population remains limited, particularly in Asian cohorts. This study aimed to evaluate the clinical role and real-world outcomes of PRRT in Japanese patients with somatostatin receptor-positive metastatic rectal NETs. Methods: We retrospectively analyzed 20 patients with metastatic rectal NETs who underwent PRRT at the University Hospital Basel (Switzerland) and Yokohama City University Hospital (Japan) between April 2015 and May 2023. The primary endpoint was progression-free survival (PFS), and secondary endpoints included disease control rate (DCR), overall response rate (ORR), overall survival (OS), and adverse events (AEs). Exploratory subgroup analyses were performed according to clinical characteristics, including changes in serum neuron-specific enolase (NSE). Results: The median PFS was 18.9 months (95% CI, 13.5–24.3), and the median OS was 30.3 months (95% CI, 18.9–41.7). The DCR was 80.0%, and the ORR was 15.0%. Treatment responses included partial response in 3 patients, stable disease in 13, progressive disease in 3, and not evaluable in 1. The most common AEs were lymphopenia and anemia, and no secondary malignancies were observed. No clinical factors were significantly associated with PFS; however, higher baseline NSE levels showed a trend toward shorter PFS. Patients with post-treatment declines in NSE showed more favorable treatment responses. Conclusions: PRRT may provide durable disease control with a favorable safety profile in Japanese patients with metastatic rectal NETs. However, these findings should be interpreted with caution given the small sample size and heterogeneous patient population. Baseline NSE elevation and early post-treatment declines may serve as potential prognostic indicators. These results are hypothesis-generating and warrant validation in larger, multicenter studies. Full article

Background/Objectives: Mycoplasma genitalium is an emerging cause of sexually transmitted infections (STIs) and is increasingly recognized for its association with cervicitis and pelvic inflammatory disease. However, prevalence data in specific Japanese subpopulations, particularly comparing pregnant and non-pregnant women, remains limited. This study aimed to determine the prevalence of M. genitalium and its co-infection rates with Chlamydia trachomatis and Neisseria gonorrhoeae among Japanese women. Methods: A cross-sectional study was conducted using vaginal swab specimens collected between April 2021 and November 2022 from patients visiting two clinics in Gifu, Japan. The study population comprised 2138 non-pregnant women presenting with urogenital symptoms or sexual contact history, and 236 pregnant women undergoing routine antenatal screening. Detection was performed using real-time polymerase chain reaction assays on the cobas^® 8800 system (Roche Diagnostics). Results: Among non-pregnant women, the overall prevalence was 3.8% (82/2138) for M. genitalium, 3.4% (72/2138) for C. trachomatis, and 0.4% (9/2138) for N. gonorrhoeae. Co-infection rates were low; M. genitalium and C. trachomatis co-infection was observed in 0.2% of cases. Among pregnant women, the prevalence was 3.8% (9/236) for both M. genitalium and C. trachomatis, and 0.4% (1/236) for N. gonorrhoeae. No statistically significant differences in prevalence were observed between pregnant and non-pregnant women for any pathogen. Conclusions: The prevalence of M. genitalium in this Japanese cohort was comparable to that of C. trachomatis in both pregnant and non-pregnant women, highlighting its significance as a major STI pathogen. These findings underscore the importance of including M. genitalium in routine STI screening panels for symptomatic women and antenatal care to prevent reproductive health complications. Given the high rates of antimicrobial resistance documented in Japanese M. genitalium strains, specific diagnostic testing is essential to enable targeted, resistance-guided therapy. Full article

Background: Underweight (BMI < 18.5 kg/m²) remains prevalent among young Japanese women but lacks standardized measurement approaches. We compared four analytical methods and identified discrepancies. Methods: A retrospective analysis of 883 underweight women aged 20–29 years followed for 6.1 ± 4.2 years was performed. We compared (1) year-to-year transitions, (2) state occupancy, (3) the Aalen–Johansen estimator, and (4) Kaplan–Meier Survival Analysis. We performed bidirectional flow analysis quantifying inflow/outflow rates, BMI distribution analysis, and time-weighted classification. Results: Methods 1 and 4 showed 31-point discrepancies (78.1% vs. 47.1% in women). In bidirectional flow, inflow exceeded outflow at ages 22–27 (35.7%/yr vs. 20.7%/yr, outflow/inflow ratio: 0.58), balanced at ages 27–37 (ratio: 1.02) and showed outflow-dominant pattern at ages 37–47 (ratio: 4.92). BMI clustered at 18.0–19.0 kg/m² (42.7%); 69.4% crossed the threshold once. Time-weighted classification revealed four phenotypes: persistent (≥75% time underweight; 40.1%, BMI: 17.54 kg/m²), moderate (50–74%; 17.6%, BMI: 18.40 kg/m²), intermittent (25–49%; 17.6%, BMI: 18.97 kg/m²), and transient (<25%; 24.8%, BMI: 19.49 kg/m²). The moderate + intermittent group showed yo-yo phenotypes (35.2%). Conclusions: Underweight in young Japanese women should be viewed as a heterogeneous dynamic nutritional state. The methodological discrepancy, threshold crossing, and phenotypic classification show that BMI-defined underweight comprises distinct patterns. Cross-sectional data evaluation may lead to incorrect assessments. Future research examining relationships between longitudinal low body weight subgroups and clinical outcomes could identify at-risk populations within the underweight group. Full article

The blackfin flounder (Glyptocephalus stelleri) is an important demersal fish species widely distributed in the Northwest Pacific and represents a valuable fisheries resource in Korea and Japan. Understanding the genetic diversity and population connectivity of exploited marine species is essential for effective fisheries management and conservation. In this study, mitochondrial DNA control region sequences (401 bp) were analyzed from 62 individuals collected from Jumunjin, Korea, and Maizuru, Japan, to assess genetic diversity, demographic history, and population structure. Sequence analysis identified 48 haplotypes, revealing exceptionally high haplotype diversity (h = 0.982 ± 0.010) and relatively low nucleotide diversity (π = 0.011 ± 0.006). Neutrality tests and mismatch distribution analyses indicated a historical demographic expansion during the Pleistocene. No significant genetic differentiation was detected between the two sampling locations (F_ST = −0.004, p > 0.05), suggesting strong genetic connectivity between Korean and Japanese samples based on mitochondrial DNA data. These findings provide important baseline genetic information for understanding population connectivity and may contribute to the coordinated management of blackfin flounder fisheries in the Northwest Pacific. Full article

Background/Objective: Women with a history of gestational diabetes mellitus (GDM) are at increased risk of type 2 diabetes mellitus (T2DM), dysglycemia, and dyslipidemia. However, the role of postpartum weight change in long-term metabolic outcomes remains unclear. Here, we determined the long-term incidence of dysglycemia and dyslipidemia after GDM and evaluated whether postpartum changes in body mass index (BMI) independently predicted these outcomes. Methods: This single-center prospective cohort study included 205 Japanese women diagnosed with GDM. All participants underwent a 75 g oral glucose tolerance test at 6–12 weeks postpartum. The incidence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), T2DM, and dyslipidemia was evaluated over a median follow-up of 3.6 years. Cumulative incidence was estimated using the Kaplan–Meier method, and Cox proportional hazards models identified independent risk factors, particularly postpartum BMI change. Results: During follow-up, 42.4%, 6.3%, and 35.6% of women developed IFG or IGT (prediabetes), T2DM, and dyslipidemia, respectively. The estimated cumulative incidence rates at 6 years postpartum were 57.1% and 50% for IFG/IGT and dyslipidemia, respectively, whereas the 5-year incidence of T2DM was 10.3%. Postpartum BMI increase was independently associated with new-onset dysglycemia. No independent predictor of T2DM progression was identified. Dyslipidemia was independently associated with higher pre-pregnancy BMI and multiparity, whereas postpartum BMI change was not independently associated after multivariable adjustment. Conclusions: Postpartum BMI change was independently associated with dysglycemia in women with a history of GDM. These findings suggest that postpartum weight change may help identify women at higher risk of subsequent metabolic abnormalities, particularly dysglycemia, in this high-risk population, although causal relationships cannot be inferred from this observational study. Full article

Background/Objectives: Intramuscular fat deposition is a key determinant of beef quality in Japanese Black cattle, and the fat area ratio of the rib eye (FAR) is highly correlated with Beef Marbling Standard scores. Methods: To identify genetic variants underlying variation in the FAR, we conducted a genome-wide association study (GWAS) followed by whole-genome sequence–based fine mapping in a Hyogo Japanese Black population (n = 432). Animals were genotyped using the Illumina BovineSNP50v3 BeadChip, and association analysis was performed using residuals derived from a linear mixed model accounting for fixed and random effects. Results: A significant association signal was detected on BTA17 (λ = 1.09), with the top single nucleotide polymorphism (SNP) located at 17:72,329,662 (p = 3.60 × 10⁻⁶). To refine the candidate region, we analyzed whole-genome resequencing data from 42 Hyogo Japanese Black cattle and identified a distinct linkage disequilibrium (LD) block spanning 71–74 Mbp on BTA17. Among 4292 variants within genes showing LD (r² ≥ 0.1) with the top SNP, 96 variants with strong LD and predicted functional effects were selected for validation. Genotyping in the Hyogo population revealed that a missense variant in gamma-glutamyltransferase 1 (GGT1) (c.589G>A, p.Asp197Asn) showed the strongest association with FAR (p = 3.89 × 10⁻⁶). A 5′UTR variant in GGT1 (c. −256G>T) and a missense variant in solute carrier family 5 member 1 (SLC5A1) (c.32C>T, p.Thr11Met) also exhibited significant associations and strong LD with the top SNP (r² > 0.7). GGT1 is involved in glutathione metabolism, whereas SLC5A1 encodes a sodium–glucose cotransporter implicated in nutrient sensing and metabolic regulation. Conclusions: Although functional validation is required, these variants represent strong positional and biological candidates underlying the BTA17 quantitative trait loci (QTL). The identified polymorphisms may provide useful molecular markers for optimizing genetic improvement of marbling-related traits within the Hyogo Japanese Black population. Full article

Background/Objectives: Daily sleep patterns are associated with cognitive health and Alzheimer’s disease (AD). However, it remains unclear how suboptimal irregular sleep manifests in AD from the preclinical stage to dementia. This study aimed to establish the dose–response association between sleep irregularity and psychometrically defined stage-specific AD as well as executive dysfunction, among adults with subjective cognitive and sleep issues. Methods: Cross-sectional data were obtained from 532 Japanese adults (mean age = 63.9 years) between March 2023 and April 2024. Sleep irregularity was quantified using the Sleep Regularity Index (SRI) with 24/7 accelerometer data. A modified Poisson regression with cubic splines was performed to establish the dose–response association. Results: This study identified novel non-linear associations. The prevalence ratios of cognitive impairment, defined as being in the preclinical and more advanced stages of AD, significantly declined beyond a median SRI of 60. Participants within this SRI range also showed significantly lower prevalence ratios of poorer Trail Making Test B performance. All results were independent of age, sleep duration, and risk of depression. Conclusions: Maintaining balanced-to-regular daily sleep patterns might be optimal for AD progress from its preclinical stages, with a potential benchmark at SRI of 60, especially for those individuals at risk for cognitive decline and sleep disorders. Further research is needed to replicate this benchmark in diverse populations and to evaluate the effect of rigid sleep regularity on cognitive health. Full article

Background/Objectives: Parents of preschool children may adopt dietary practices intended to promote height growth. However, the correlates of such practices in the general population remain unclear. Methods: This web-based cross-sectional study included 1362 mothers of Japanese children aged 3–5 years. Mothers were assigned to the height-related dietary practice group if they had ever used dietary practices to promote their child’s height growth; all other mothers were classified into the no-practice group. The questionnaire assessed child and parental characteristics, including anthropometric measurements, history of short stature (height < −2 SD at any time point), history of food allergy, maternal information-seeking behavior regarding child growth, and current dietary intake. Associations with height-related dietary practices were examined using a multiple logistic regression analysis. Results: In total, 531 mothers (39.0%) were classified into the practice group. Older child age, history of short stature, history of food allergy, and information-seeking behavior were positively associated with height-related dietary practices, whereas parental height was inversely associated. Milk and dairy products are the most frequently used foods for height promotion. Children in the practice group were more likely to meet the cutoffs for milk/dairy products and fish, but their overall attainment was low. In the analyses of retrospectively reported height SD score trajectories, no group-by-time interactions were observed. Conclusions: Height-related dietary practices were associated with growth-related concerns and parental characteristics rather than differential height gain over time. Health guidance may help parents adopt balanced diets that support overall nutrition and healthy growth rather than focusing on specific foods. Full article

Background/Objectives: MYO7A is known to be the genetic cause of Usher syndrome type 1, as well as autosomal dominant and autosomal recessive non-syndromic hearing loss. In general, autosomal dominant MYO7A-associated hearing loss shows progressive high-frequency, sloping hearing loss. However, several variants are associated with low-frequency hearing loss. MYO7A-associated low-frequency hearing loss is relatively rare, and the clinical details remain unclear. Methods: A total of 18,475 Japanese patients with hearing loss were recruited. Targeted massively parallel sequencing of 158 deafness-related genes was performed, and individuals with variants related to MYO7A-associated low-frequency hearing loss were identified. Results: Among 18,475 hearing loss patients, we identified 60 patients from 44 unrelated families carrying five variants (p.[Asn140Lys; Glu1835Gln], p.Leu479Pro, p.Leu656Val, p.Gly660Arg, and p.Arg668His) for MYO7A-associated low-frequency hearing loss. Patients identified in this study initially showed postlingual-onset mild-to-moderate low-frequency hearing loss; however, high-frequency hearing also deteriorated after the fourth decade, eventually leading to moderate-to-severe flat-type hearing loss. In addition, we performed haplotype analysis for the recurrent variant c.1436T>C:p.Leu479Pro identified in this study and found that this variant is a founder mutation in the Japanese population. Conclusions: In this study, we were able to clarify the specific features of MYO7A-related low-frequency hearing loss in a significant number of patients. In particular, we clarified the details of hearing deterioration at each frequency. Our findings will be useful for providing more appropriate treatment and follow-up for MYO7A-associated low-frequency hearing loss. Full article

Background and Objectives: Non-O ABO blood groups have been linked to higher coronary risk, plausibly via hemostatic and lipid pathways. However, evidence in Japanese populations and imaging-defined disease is limited. We examined whether ABO status relates to serum lipids and coronary CT imaging findings in Japanese adults. Materials and Methods: We reviewed adults who underwent coronary CT angiography (CCTA) at our institution. After prespecified exclusions, 865 patients comprised the imaging cohort. For lipid analyses, we excluded patients receiving lipid-lowering therapy at the time of blood sampling, leaving 636 patients (lipid subset). ABO blood group was obtained from the medical record as recorded at registration (patient-reported) and was not re-confirmed by laboratory testing for this study. Outcomes were any coronary artery calcium (Agatston score > 0) and ≥50% luminal stenosis on CCTA. Results: In the lipid subset (n = 636), coronary calcium was present in 44–54% of patients across the four ABO groups and did not differ across groups (p = 0.33). Among assessable scans in the imaging cohort, ≥50% stenosis did not differ across the four ABO groups. In multivariable models (n = 636), older age, male sex, hypertension, and diabetes were independently associated with both outcomes (CAC presence and ≥50% stenosis) (all p < 0.05). For ≥50% stenosis, higher High-Density Lipoprotein-cholesterol (HDL-C) was additionally associated with lower odds (p < 0.05). ABO status (O vs. non-O) was not independently associated with either outcome. Conclusions: In Japanese adults undergoing CCTA, type O blood was tied to lower HDL-C and higher diastolic pressure—features that track with cardiometabolic risk—yet ABO type did not independently relate to coronary calcium or CT-defined stenosis once standard risk factors were considered. These data suggest that, in this setting, ABO adds little beyond conventional risk profiling. Full article

Background: Sleep quality and mental health are important concerns for esports competitors. However, epidemiological data regarding sleep quality and psychological distress among high-level esports players remain limited. Objective: This study aimed to examine sleep quality and mental health status among high-level esports competitors in Japan and to identify factors associated with psychological distress. Methods: This cross-sectional study included 275 competitors (269 males, 3 females, and 3 who did not report sex) participating in the 2023 National Prefectural Esports Championship. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), psychological distress using the Kessler Psychological Distress Scale (K6), and depressive symptoms using the Patient Health Questionnaire-9 (PHQ-9). Multivariable logistic regression analyses were performed to identify associated factors. Results: The response rate was 61.8% (275/445). Poor sleep quality (PSQI > cut-off) was observed in 38.5% of competitors. Based on the K6, 24.4% reported psychological distress above the mild threshold, and 29.5% reported mild or greater depressive symptoms according to the PHQ-9. Overall mental health levels were comparable to those reported in previous studies of general populations. Nighttime esports training was significantly associated with psychological distress (adjusted odds ratio 3.80; 95% confidence interval 1.50–9.64; p = 0.005). Conclusions: More than one-third of Japanese esports competitors experience poor sleep quality, and approximately one-quarter report mild or greater psychological distress. Nighttime esports training may be an important factor associated with mental health among competitors. Further longitudinal studies are warranted to clarify temporal relationships and to examine whether reducing nighttime training is associated with improved mental health outcomes among esports competitors. Full article

Older patients with unresectable locally advanced non-small-cell lung cancer (NSCLC) frequently receive concurrent chemoradiotherapy (CCRT) with daily low-dose carboplatin; however, real-world data on its efficacy, safety, and prognostic factors remain limited. We aimed to retrospectively evaluate the clinical outcomes of this regimen and examined whether systemic inflammation-based indices predict prognosis in this setting. We reviewed 52 consecutive patients with locally advanced NSCLC treated with first-line CCRT using daily low-dose carboplatin at three Japanese institutions between April 2007 and December 2019. The median progression-free survival (PFS) and overall survival (OS) were 11.5 and 40.1 months, respectively. Twenty patients received durvalumab as consolidation therapy. In the overall cohort, multivariate analysis identified the Glasgow Prognostic Score (GPS) as an independent predictor of PFS. A GPS of 0–1 was also associated with a significantly longer OS in univariate analysis. CCRT with daily low-dose carboplatin provided durable disease control with acceptable toxicity in older patients with unresectable stage II/III NSCLC. The GPS appears to be a simple marker for PFS in this population and may aid in pretreatment risk stratification alongside histology and consolidation strategies. Full article