Association between Fish Intake and Serum Testosterone Levels in Older Males: The Hitachi Health Study II.

Background: Fish are rich in omega-3 polyunsaturated fatty acids and vitamin D, which can promote testosterone synthesis and secretion. However, some contaminants present in fish may disrupt testosterone production. Objective: This study aimed to investigate the association between fish intake (total, fatty, and lean fish) and serum testosterone levels in older males. Methods: This cross-sectional study included 1545 Japanese males aged 60-69 y who participated in the baseline survey of the Hitachi Health Study II. Fish intake was estimated using a validated brief-type self-administered diet history questionnaire. Total testosterone levels were measured by chemiluminescence immunoassay. Multivariable linear regression analysis was used to analyze the association between fish intake and serum testosterone levels. Results: Higher total fish intake was associated with higher levels of serum testosterone, with an adjusted mean [95% confidence interval (CI) of 5.63 (5.43, 5.83) and 5.99 (5.78, 6.20)] ng/mL for the 1st and 4th quartiles of total fish intake, respectively (P for trend = 0.06). When analyzing fatty and lean fish separately, higher intake of lean fish, but not fatty fish, was associated with higher levels of serum testosterone: adjusted mean (95% CI): 5.63 (5.43, 5.82) and 6.00 (5.79, 6.20) ng/mL for the 1st and 4th quartiles of lean fish intake, respectively (P for trend = 0.01). Conclusions: Among older males, higher intake of total fish, particularly lean fish, was associated with higher serum testosterone levels. Curr Dev Nutr 20xx;x:xx.

Prevalence of osteosarcopenia and its association with mortality and fractures among patients undergoing hemodialysis.

INTRODUCTION: Osteosarcopenia is an age-related syndrome characterized by the coexistence of osteoporosis and sarcopenia. Little is known about the clinical implications of osteosarcopenia among patients undergoing hemodialysis. This study investigated the prevalence of osteosarcopenia and its association with all-cause mortality and fractures in this population. MATERIALS AND METHODS: This retrospective cohort study included outpatients undergoing hemodialysis in Japan. Sarcopenia was defined according to the recommendations of the Asian Working Group for Sarcopenia 2019. Osteoporosis was defined as a T-score of the calcaneus bone < - 2.5. We divided patients into three groups: robust (no osteoporosis or sarcopenia), osteoporosis or sarcopenia alone (osteoporosis without sarcopenia or sarcopenia without osteoporosis), and osteosarcopenia (osteoporosis and sarcopenia). Cox proportional-hazard and negative binomial regression models were used to estimate the associations between osteosarcopenia and all-cause mortality and fractures. RESULTS: Among the 328 patients (mean age, 65.5 ± 11.3 years; men, 59.1%), the prevalence of osteosarcopenia was 22.9%. During the follow-up period (1972 person-years), 131 deaths and 113 fractures occurred. Patients with osteoporosis or sarcopenia alone (hazard ratio 1.36; 95% confidence interval 0.85-2.18) and osteosarcopenia (hazard ratio 2.13; 95% confidence interval, 1.23-3.68) showed a higher risk of all-cause mortality than the robust group. Similar results were observed for the risk of fractures in patients with osteosarcopenia. CONCLUSIONS: Patients undergoing hemodialysis showed a high prevalence of osteosarcopenia, and osteosarcopenia was associated with a poor prognosis in this patient population. Assessing osteosarcopenia may be useful for accurate prognostic stratification of patients undergoing hemodialysis.

Vitamin D deficiency during the coronavirus disease 2019 (COVID-19) pandemic among healthcare workers.

BACKGROUND & AIMS: Vitamin D deficiency is a common nutritional problem worldwide that may have worsened during the coronavirus disease 2019 (COVID-19) pandemic. The present study sought to examine the prevalence and correlates of vitamin D deficiency among healthcare workers three years after the start of the COVID-19 pandemic. METHODS: Participants comprised 2543 staff members from a medical research institute, who completed a questionnaire and donated blood samples in June 2023. 25-hydroxyvitamin D (25[OH]D) levels were measured using an electrochemiluminescence immunoassay. Logistic regression was used to calculate the odds ratio and its 95% confidence interval while adjusting for covariates. RESULTS: The proportions of participants with vitamin D insufficiency (25[OH]D 20-29 ng/mL) and deficiency (25[OH]D < 20 ng/mL) were 44.9% and 45.9%, respectively. In a multivariable-adjusted model, factors associated with a higher prevalence of vitamin D deficiency included younger age, female sex, fewer hours of daytime outdoor physical activity during leisure time (without regular use of sunscreen), lower intake of fatty fish, no use of vitamin D supplements, smoking, and no alcohol consumption. Occupational factors, including shift work, were not independently associated with vitamin D deficiency. CONCLUSIONS: Our results suggest that vitamin D insufficiency and deficiency are highly prevalent among healthcare workers. Health education regarding lifestyle modifications for this occupational group are warranted to improve their vitamin D status in the COVID-19 era.

Comparison of waist circumference and waist-to-height ratio as predictors of clustering of cardiovascular risk factors among middle-aged people in rural Khanh Hoa, Vietnam.

OBJECTIVE: Given the population-level variation in stature, a universal cut-off for waist circumference (WC) may not be appropriate for some populations. We compared the performance of WC and waist-to-height ratio (WHtR) to detect the clustering of cardiovascular disease (CVD) risk factors in rural Vietnam. METHODS: We obtained data from a baseline survey of the Khanh Hoa Cardiovascular Study comprising 2942 middle-aged residents (40-60 years). We used areas under the receiver operating characteristics curve (AUROC), net reclassification index (NRI), and integrated discrimination improvement (IDI) to compare the performance of WC and WHtR in predicting CVD risk clustering (≥2 of the following risk factors: hypertension, diabetes, dyslipidemia, and elevated C-reactive protein). RESULTS: The optimal cut-off values for WC were 81.8 and 80.7 cm for men and women, respectively. Regarding the clustering of CVD risk factors, the AUROC (95% CI) of WC and WHtR were 0.707 (0.676 to 0.739) and 0.719 (0.689 to 0.749) in men, and 0.682 (0.654 to 0.709) and 0.690 (0.663 to 0.717) in women, respectively. Compared with WC, WHtR had a better NRI (0.229; 0.102-0.344) and IDI (0.012; 0.004-0.020) in men and a better NRI (0.154; 0.050-0.257) in women. CONCLUSIONS: The optimal WC cut-off for Vietnamese men was approximately 10 cm below the recommended Asian cut-off. WHtR might perform slightly better in predicting the clustering of CVD risk factors among the rural population in Vietnam.

Molecular basis promoting centriole triplet microtubule assembly.

The triplet microtubule, a core structure of centrioles crucial for the organization of centrosomes, cilia, and flagella, consists of unclosed incomplete microtubules. The mechanisms of its assembly represent a fundamental open question in biology. Here, we discover that the ciliopathy protein HYLS1 and the ß-tubulin isotype TUBB promote centriole triplet microtubule assembly. HYLS1 or a C-terminal tail truncated version of TUBB generates tubulin-based superstructures composed of centriole-like incomplete microtubule chains when overexpressed in human cells. AlphaFold-based structural models and mutagenesis analyses further suggest that the ciliopathy-related residue D211 of HYLS1 physically traps the wobbling C-terminal tail of TUBB, thereby suppressing its inhibitory role in the initiation of the incomplete microtubule assembly. Overall, our findings provide molecular insights into the biogenesis of atypical microtubule architectures conserved for over a billion years.

Coffee and green tea consumption with the risk of COVID-19 among the vaccine recipients in Japan: a prospective study.

BACKGROUND: While coffee and green tea have been suggested to have immunoprotective effects, it remains elusive whether they can decrease the risk of COVID-19. OBJECTIVE: We prospectively examined the association between coffee and green tea consumption and the risk of COVID-19 among mRNA vaccine recipients during the epidemic of the Omicron variant. METHOD: Participants were 2,110 staff (aged 18 to 76 years) of a large medical facility in Tokyo, who attended a serosurvey in June 2022, predominatly received ≥3 doses of vaccine, and were followed for COVID-19 until December 2022. Coffee and green tea consumption was ascertained via a questionnaire. COVID-19 was identified through the in-house registry. Cox proportional hazards model was used to estimate the hazard ratios (HRs) of COVID-19 across the categories of beverage consumption. RESULT: During 6 months of follow-up, 225 (10.6%) cases of COVID-19 were identified. Contrary to the expectation, higher consumption of coffee was associated with a significant increase in the risk of COVID-19; multivariable-adjusted HRs (95% CI) was 1.00, 0.92 (0.62-1.35), 1.48 (0.99-2.22), and 1.82 (1.20-2.76) for <1 cup/day, 1 cup/day, 2 cups/day, and ≥3 cups/day, respectively (p trend=0.003). Green tea consumption was not significantly associated with the risk of COVID-19. The association with coffee was attenuated if serologically detected infection was added to the cases. CONCLUSION: In a cohort of Japanese hospital staff who received COVID-19 vaccine, higher consumption of coffee was associated with an increased risk of COVID-19 during the epidemic of the Omicron variant. There was no evidence of a significant association between green tea consumption and COVID-19 risk.

TBI, etoposide, and cyclophosphamide conditioning for intermediate-risk relapsed childhood acute lymphoblastic leukemia.

BACKGROUND: In children with intermediate-risk relapsed acute lymphoblastic leukemia (ALL), allogeneic hematopoietic stem cell transplantation (allo-HSCT) has markedly improved the outcome of patients with an unsatisfactory minimal residual disease (MRD) response. Total body irradiation (TBI), etoposide (ETP), and cyclophosphamide (CY) have been shown to be equivalent to or better than TBI + ETP for conditioning, so we hypothesized that even greater survival could be achieved due to recent advances in HSCT and supportive care. PROCEDURE: We prospectively analyzed the efficacy and safety of allo-HSCT with a unified conditioning regimen of TBI + ETP + CY in children with intermediate-risk relapsed ALL, based on MRD in the bone marrow after induction, from the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) ALL-R08-II nationwide cohort (UMIN000002025). RESULTS: Twenty patients with post-induction MRD ≥ 10-3 and two not evaluated for MRD underwent allo-HSCT. Engraftment was confirmed in all patients, and no transplantation-related mortality was observed. The 3-year event-free survival and overall survival rates after transplantation were 86.4% ± 7.3% and 95.5% ± 4.4%, respectively. CONCLUSION: Allo-HSCT based on post-induction MRD with TBI + ETP + CY conditioning was feasible in Japanese children with intermediate-risk relapsed ALL.

Association between Physical Frailty and Sleep Disturbances among Patients on Hemodialysis: A Cross-Sectional Study.

INTRODUCTION: Among patients on hemodialysis (HD), physical frailty and sleep disturbances are not only common but also associated with adverse outcomes. The aim of this study was to evaluate the association between physical frailty and sleep disturbances in patients on HD. METHODS: This cross-sectional study was conducted from June 2017 to March 2021, with outpatients receiving HD 3 times a week at two dialysis facilities in Japan. Sleep disturbances were identified with the Athens Insomnia Scale (AIS). Physical frailty was defined using the Fried Frailty Phenotype. Patients were classified as "non-frailty (number of frailty components: 0-2)" or "frailty (3-5)." We examined the association of sleep disturbances with physical frailty and its components by performing a logistic regression analysis. RESULTS: We analyzed 360 patients (mean age 65.6 years; 62% men). Eighty-one patients (23%) were classified into the group with frailty, and the mean AIS score was 5.2 ± 4.2 points. After adjusting for clinical characteristics, increasing the AIS score per 1 point was associated with higher odds of physical frailty (odds ratio, 1.12; 95% confidence interval, 1.05-1.20; p < 0.01). As for the frailty components, exhaustion, low physical activity, and weak grip strength showed an association with sleep disturbances (all p < 0.05). CONCLUSIONS: Sleep disturbances were independently associated with physical frailty in patients on HD. Future studies are warranted to investigate the causality between physical frailty and sleep disturbances in this population.

Isoflavone intake and depressive symptoms among workers.

BACKGROUND & AIM: High intake of isoflavones has been reported to be associated with decreased prevalence of depressive symptoms. However, no prospective study has examined this association. We prospectively investigated the association between isoflavone intake and depressive symptoms in a Japanese working population. METHODS: Participants were 1162 workers (1033 men and 129 women aged 18-68 years) without depressive symptoms at baseline. Dietary intake was assessed using a validated self-administered diet history questionnaire. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale. Cox proportional hazards regression for interval-censored data was used to estimate the hazard ratio of depressive symptoms (CES-D ≥16) according to the tertile of isoflavone intake with adjustment for covariates. RESULTS: During 5065 person-years of follow-up, 276 (23.8 %) workers were newly identified as having depressive symptoms. Isoflavone intake was not associated with risk of depressive symptoms. After adjustment for lifestyle and dietary factors and baseline CES-D score, the multivariable-adjusted hazard ratios (95 % confidence interval) for the lowest through highest tertile of isoflavone intake were 1.00 (reference), 0.93 (0.66-1.31), and 0.93 (0.62-1.38) (P for trend = 0.70). CONCLUSIONS: Our findings suggest that higher isoflavone intake is not associated with decreased risk of depressive symptoms among Japanese.

The association between antipyretic analgesics use and SARS-CoV-2 antibody titers following the second dose of the BNT162b2 mRNA vaccine: An observational study.

Antipyretic analgesics are used to manage and control symptoms occurring after vaccination, but may hamper immunogenicity or vaccine efficacy. We examined the association between prophylactic or therapeutic use of antipyretic analgesics and SARS-CoV-2 antibody titers for vaccine recipients. Data were obtained from 1,498 staff members of a medical and research institution in Tokyo, Japan, who had received the second dose of the BNT162b2 vaccine. We quantitatively measured anti-SARS-CoV-2 spike protein IgG titers in the participants three months after vaccination. The prophylactic and therapeutic use of antipyretic analgesics was ascertained via a questionnaire. A linear regression model was used to examine the association between antipyretic analgesic use and log-transformed anti-SARS-CoV-2 spike protein IgG titers. Based on model parameters, we estimated geometric mean titers (GMT) and the corresponding 95 % confidence intervals (CI). The results showed that IgG titers in vaccine recipients who used antipyretic analgesics therapeutically was higher than the titers in those who did not (geometric mean ratio [GMR] = 1.26, 95 % CI = 1.17-1.34) with GMTs being 6,147 (95 % CI = 5,833-6,460) and 4,895 (95 % CI = 4,676-5,115) for those who used antipyretic analgesics therapeutically and those who did not, respectively. The association was attenuated, but remained statistically significant after adjusting for symptoms (GMR = 1.14, 95 % CI = 1.06-1.23). We did not find any evidence of significant association in relation to the prophylactic use of antipyretic analgesics (GMR = 0.96, 95 % CI = 0.84-1.10), with GMTs being 5,245 (95 % CI = 4,577-5,913) and 5,452 (95 % CI = 5,258-5,645) for those who used antipyretic analgesics prophylactically and those who did not, respectively. In conclusion, we did not find any evidence of suppression of the humoral response after the second dose of SARS-CoV-2 vaccination by prophylactic or therapeutic use of antipyretic analgesics.

Preinfection Neutralizing Antibodies, Omicron BA.5 Breakthrough Infection, and Long COVID: A Propensity Score-Matched Analysis.

BACKGROUND: Data are limited on the role of preinfection humoral immunity protection against Omicron BA.5 infection and long coronavirus disease (COVID) development. METHODS: We conducted nested case-control analysis among tertiary hospital staff in Tokyo who donated blood samples in June 2022 (1 month before Omicron BA.5 wave), approximately 6 months after receiving a third dose of COVID-19 mRNA vaccine. We measured live virus-neutralizing antibody titers against wild type and Omicron BA.5, and anti-receptor-binding domain (RBD) antibody titers at preinfection, and compared them between cases and propensity-matched controls. Among the breakthrough cases, we examined association between preinfection antibody titers and incidence of long COVID. RESULTS: Preinfection anti-RBD and neutralizing antibody titers were lower in cases than controls. Neutralizing titers against wild type and Omicron BA.5 were 64% (95% confidence interval [CI], 42%-77%) and 72% (95% CI, 53%-83%) lower, respectively, in cases than controls. Individuals with previous Omicron BA.1/BA.2 infections were more frequent among controls than cases (10.3% vs 0.8%), and their Omicron BA.5 neutralizing titers were 12.8-fold higher than infection-naive individuals. Among cases, preinfection antibody titers were not associated with incidence of long COVID. CONCLUSIONS: Preinfection immunogenicity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may play a role in protecting against the Omicron BA.5 infection but not preventing long COVID.

The association between living alone and depressive symptoms and the role of pet ownership among Japanese workers.

BACKGROUND: Living alone has been positively associated with the prevalence of depressive symptoms. We examined how a combination of living alone and pet ownership relates to depressive symptoms. METHODS: As part of the Japan Epidemiology Collaboration on Occupational Health Study, we conducted a survey on health-related lifestyles, including living arrangements and pet ownership, among 12,763 employees of five companies in 2018-2021. Depressive symptoms were assessed using the 11-item Center for Epidemiological Studies-Depression Scale (cutoff score ≥ 9). A Poisson regression model with a robust variance estimator was used to calculate prevalence ratio and 95% confidence interval (CI) while adjusting for covariates. RESULTS: Among the participants, 30.9% were depressed, 17.7% had pets, and 29.1% lived alone. Compared to individuals living with others but not with a pet, those living alone and not with a pet had a 1.17 times higher prevalence ratio of depressive symptoms (95% CI: 1.08-1.26). The corresponding figures were 1.03 (95% CI: 0.95-1.11) for those living with others and pet(s) and 1.42 (95% CI: 1.18-1.69) for those living alone but with pet(s). CONCLUSION: Living alone was significantly associated with a higher prevalence of depressive symptoms. The association was rather stronger among individuals with vs. without pets. Pet ownership may not be associated with decreased depressive symptoms.

Clinical Characteristics of the Patient With Unmeasurable Ankle-Brachial Index in Endovascular Treatment.

Introduction Ankle-brachial index (ABI) is an important indicator to diagnose lower extremity arterial disease (LEAD). However, patients with unmeasurable ABI are sometimes excluded from the analysis and their clinical characteristics are poorly understood. Methods One hundred twenty-two consecutive Japanese subjects (mean age, 72 years), who underwent successful endovascular treatment (EVT) for lower extremity arteries at our hospital were retrospectively studied. Results Of the 122 patients, 23 (19%) patients presented an unmeasurable ABI before EVT. Five of 23 (22%) had still an unmeasurable ABI one day after EVT. Comorbidities including hypertension, diabetes, dyslipidemia, hemodialysis, smoking, ischemic heart disease, atrial fibrillation, and past-EVT history were not different between ABI measurable and unmeasurable patients. However, patients with unmeasurable ABI presented a significantly higher degree of Rutherford category and a smaller number of tibial vessel runoff than patients with measurable ABI before EVT (p<0.05 and p<0.01, respectively). There was no difference in the lesion site between the two groups. The event rate including all-cause mortality, re-EVT, lower limb amputation, and bypass surgery did not differ between two groups four years after EVT. ABI after four years of initial EVT did not differ between pre-EVT measurable and unmeasurable patients (0.96 vs. 0.84, p=0.48). Conclusions Patients with unmeasurable ABI before EVT were characterized by higher degree of Rutherford categorization and a small number of tibial vessel runoff, but there was no significant difference in outcomes during the follow-up period.

3',4'-Dihydroxyflavonol Attenuates Lipopolysaccharide-Induced Neuroinflammatory Responses of Microglial Cells by Suppressing AKT-mTOR and NF-κB Pathways.

Microglia-related neuroinflammation contributes to the pathogenesis of a variety of neurodegenerative disorders such as Alzheimer's disease. The synthetic flavonoid, 3',4'-dihydroxyflavonol (3,3',4'-trihydroxyflavone), has been shown to protect brain or myocardial ischemia reperfusion-induced cell death and prevent the aggregation of amyloid-ß protein, a process that causes progressive neurodegeneration in Alzheimer's disease. Here, we explored the anti-neuroinflammatory ability of 3',4'-dihydroxyflavonol in lipopolysaccharide (LPS)-activated MG6 microglial cells. 3',4'-Dihydroxyflavonol attenuated LPS-induced tumor necrosis factor-α and nitric oxide secretion in MG6 cells. LPS-induced phosphorylation of mammalian target of rapamycin (mTOR), nuclear factor-κB (NF-κB), and protein kinase B (AKT) (which are all associated with the neuroinflammatory response in microglia) were attenuated by 3',4'-dihydroxyflavonol treatment. Treatment with the mTOR inhibitor, rapamycin, NF-κB inhibitor, caffeic acid phenethyl ester, or AKT inhibitor, LY294002, also attenuated LPS-induced tumor necrosis factor-α and nitric oxide secretion in MG6 cells. LY294002 treatment attenuated LPS-induced phosphorylation of mTOR and NF-κB in MG6 cells. Hence, our study suggests that 3',4'-dihydroxyflavonol can attenuate the neuroinflammatory response of microglial cells by suppressing the AKT-mTOR and NF-κB pathways.

Haplotype-resolved chromosomal-level assembly of wasabi (Eutrema japonicum) genome.

In Japan, wasabi (Eutrema japonicum) is an important traditional condiment, and is recognized as an endemic species. In the present study, we generated a chromosome-level and haplotype-resolved reference genome for E. japonicum using PacBio CLR (continuous long reads), Illumina, and Hi-C sequencing data. The genome consists of 28 chromosomes that contain 1,512.1 Mb of sequence data, with a scaffold N50 length of 55.67 Mb. We also reported the subgenome and haplotype assignment of the 28 chromosomes by read-mapping and phylogenic analysis. Three validation methods (Benchmarking Universal Single-Copy Orthologs, Merqury, and Inspector) indicated that our obtained genome sequences were a high-quality and high-completeness genome assembly. Comparison of genome assemblies from previously published genomes showed that our obtained genome was of higher quality. Therefore, our genome will serve as a valuable genetic resource for both chemical ecology and evolution research of the genera Eutrema and Brassicaceae, as well as for wasabi breeding.

Prevalence, overlap, and prognostic impact of multiple frailty domains in older patients on hemodialysis.

BACKGROUND: Frailty is a state of increased vulnerability owing to adverse health outcomes and is recognized as a multidimensional construct. There is limited evidence on the association between multiple domains of frailty and the risk of adverse events in patients undergoing hemodialysis. We aimed to report on the prevalence, degree of overlap, and prognostic impact of multiple frailty domains in older patients undergoing hemodialysis. METHODS: We retrospectively enrolled outpatients (aged ≥60 years) undergoing hemodialysis at two dialysis centers in Japan. The physical domain of frailty was defined as slow gait speed and low handgrip strength. The psychological and social domains of frailty were defined using a questionnaire to assess depressive symptoms and define social frailty status. The outcomes were all-cause mortality, all-cause hospitalization, and cardiovascular hospitalization. Cox proportional hazard and negative binomial models were used to examine these associations. RESULTS: Among the 344 older patients (mean age, 72 years; male, 61%), 15.4% had an overlap in all three domains. Patients with a higher number of frailty domains had a higher risk of all-cause mortality, all-cause hospitalization, and cardiovascular hospitalization (P for trend = 0.001, 0.001, and 0.08, respectively). CONCLUSIONS: These results suggest that multiple-domain assessment of frailty is an important strategy to prevent adverse events in patients requiring hemodialysis.