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Objectives: Accumulating evidence from cross-sectional studies suggests that the serum creatinine-to-cystatin C ratio (CCR) may be a useful biomarker for sarcopenia. This study aimed to assess the cross-sectional and longitudinal associations of CCR with sarcopenia and its parameters in community-dwelling older adults. Design: Cross-sectional and longitudinal study. Setting and Participants: This 6-year prospective cohort study included the repeated measurement data from 1,253 Japanese residents (662 males and 591 females) aged ≥65 years who underwent medical checkups in Kusatsu and Hatoyama, Japan. A total of 4,421 observations were collected. Measurements: The CCR was grouped into quartiles by sex (Q1–Q4) using Q4 as the reference category. Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019 algorithm. Skeletal muscle mass index (SMI) measured using segmental multifrequency bioelectrical impedance analysis, handgrip strength (HGS), usual gait speed (UGS), and maximal gait speed (MGS) were measured repeatedly as sarcopenia parameters. The association of the CCR with changes in sarcopenia, SMI, HGS, UGS, and MGS during the 6-year period were analyzed using a generalized linear mixed-effects model. Results: The prevalence of sarcopenia at baseline was 13.1% (11.9% in males and 14.5% in females). In a cross-sectional analysis, the CCR quartile was inversely associated with sarcopenia and was positively associated with SMI, HGS, and MGS (P for trend < 0.001). In a longitudinal analysis during the 6 years, a significant increase in sarcopenia in Q2 (B = 1.1% point/year; P = 0.026 for group-by-time interaction) and significant declines in SMI (B = −0.01 kg/m2/year; P = 0.044 for group-by-time interaction) and MGS (B = −0.008 m/sec/year; P = 0.041 for group-by-time interaction) in Q1 were observed compared with Q4. However, the dose-response relationship was significant only for MGS (P = 0.033 for trend). No significant group-by-time interaction was observed for HGS. CCR was not significantly associated with UGS either cross-sectionally or longitudinally. Conclusions: CCR is a useful biomarker regarding the status of sarcopenia. It may be used for sarcopenia screening even in older adults whose physical function is difficult to assess. However, further longitudinal studies are needed to determine whether CCR can be a predictor of future sarcopenia. [ABSTRACT FROM AUTHOR]

Orono-shima Island is a remote Island in the Tsushima Strait, it is 4.3km around. Since ancient times, it has been a landmark when crossing from the Korean Peninsula to Japanese archipelago via Tsushima Island and Iki Island. However, large-scale ruins and burial mounds are not known on Orono-shima Island until now. During my four years on the island, the author walked all over the island for terrain survey. As a result, the author discovered a topography like keyhole tomb which is a characteristic Japanese burial mound, on the northern cape of the island. It could be up to 150m in size, one of the largest around Kyusyu Island. There is no burial mound comparable to this on a remote island in Japan. Therefore, we created a 3D image using a drone Laser surveying of this terrain and we compared the results with another keyhole tomb. In addition, we analyzed the image of infrared radiation of Orono-shima Island took by Landsat8. In conclusion, it was speculated that this topography was the prototype of the oldest type of keyhole cairn tomb in Japan. The topography of the northern part of Orono-shima could be regaining the missing link between the cairn on the Korean Peninsula of the first century and the oldest type of keyhole cairn tomb in Japan of the third century. [ABSTRACT FROM AUTHOR]

In 2018, the ancient tomb was discovered in Tagawa, Fukuoka. The sizes of the tomb were measured by UAV. The length is 443 m, the diameter is 152 m, and the height is 33 m: the second biggest mound in Japan. Chinese history book, Sanguozhi (Chen, 280) reads Yamatai country occupied 27 countries in Japan in the 3rd century by the queen Himiko. The location of Yamatai was 840 km south from Soul with 70000 families, and the size of Himiko's tomb was 150 m diameters. The locations of Yamatai country and Himiko's tomb are still unknown. From Sanguozhi, the optimum location was estimated with the direction, the distance and family numbers. Family numbers were estimated from the river watershed areas. Kyushu islands have 28 big rivers, corresponding to 28 countries described in Sanguozhi. Each river corresponded to each country, and their family number was estimated by 2.5% of the watershed area with family number / 10 a. Finally, the Chikugo river watershed was a candidate of Yamatai country. Moreover, two kinds of tombs became candidates of Himiko's tomb. [ABSTRACT FROM AUTHOR]

Objectives: This study evaluated associations of score-based and nutrient-derived dietary patterns with depressive symptoms in community-dwelling older Japanese. Design: Cross-sectional study. Setting: Community-based. Participants: 982 community-dwelling adults aged 65 years or older. Measurements: Score-based pattern was assessed by using dietary variety score (DVS), which covers 10 food group items in Japanese meals. Nutrient-derived dietary patterns were identified by using reduced rank regression (RRR), with folate, vitamin C, magnesium, calcium, iron, and zinc intakes as response variables. Depressive symptoms were assessed with the Geriatric Depression Scale. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for these dietary patterns in multivariate logistic regression analyses with potential confounders. The lowest consumption category was used as the reference group. Results: The prevalence of depressive symptoms was 13.5%. Higher DVS was associated with fewer depressive symptoms (OR=0.52, 95% CI=0.27–1.03 for the highest vs the lowest DVS; P for trend=0.031). The first RRR dietary pattern score was characterized by high intakes of fish, soybean products, potatoes, most vegetables, mushrooms, seaweeds, fruits, and green tea and a low intake of rice and was inversely associated with the prevalence of depressive symptoms (OR=0.53, 95% CI=0.30–0.92; P for trend=0.030). Conclusion: Greater dietary variety and a dietary pattern characterized by high intakes of fish, soybean products, potatoes, most vegetables, mushrooms, seaweeds, fruit, and green tea and a low intake of rice were consistently associated with lower prevalence of depressive symptoms in community-dwelling older Japanese. Therefore, both patterns identified the components of dietary habits essential to depression prevention. [ABSTRACT FROM AUTHOR]

Objectives: To examine the associations of dietary variety with body composition and physical function in community-dwelling elderly Japanese Design: Cross-sectional study. Setting: Community-based. Participants: A total of 1184 community-dwelling elderly adults aged 65 and over. Measurements: Dietary variety was assessed with a food frequency questionnaire (maximum, 10 points) that encompassed the 10 main food components of Japanese meals (meat, fish/shellfish, eggs, milk, soybean products, green/yellow vegetables, potatoes, fruit, seaweed, and fats/oils). Body composition was determined by multifrequency bioelectrical impedance analysis. Physical function was assessed by measuring grip strength and usual walking speed. Multiple linear regression analysis was used to examine the associations of dietary variety with body composition and physical function. Results: After adjusting for potential confounders, higher dietary variety scores were independently associated with higher lean mass (β (SE): 0.176 (0.049), p<0.001) and appendicular lean mass (β (SE): 0.114 (0.027), p<0.001) but not with body fat mass. Elders with a higher dietary variety score had greater grip strength and faster usual walking speed (β (SE): 0.204 (0.071), p=0.004, and β (SE): 0.008 (0.003), p=0.012, respectively). Conclusion: Greater dietary variety was significantly associated with greater lean mass and better physical function in Japanese elders. The causal relationship warrants investigation in a prospective study. [ABSTRACT FROM AUTHOR]

Summary: A high circulating osteoprotegerin (OPG) level may be a risk factor for vascular calcification and mortality in hemodialysis patients. OPG and pulse wave velocity (PWV) were measured at baseline in 151 normoalbuminemic, long-term (>3 years) Japanese hemodialysis patients who were prospectively followed for 6 years. In long-term normoalbuminemic Japanese hemodialysis patients, OPG levels were strongly linked with both arterial stiffness and worse outcome. Introduction: A high circulating OPG level is reported to be a risk factor for vascular calcification and mortality in Western chronic kidney disease (CKD) patients but it is not known if this is true for Japanese CKD patients, where a different risk profile may operate. Methods: OPG and PWV were measured at baseline in 151 normoalbuminemic, long-term (>3 years) Japanese hemodialysis patients (median age 62 years) who were prospectively followed for 6 years. Results: OPG levels were associated in multivariate analysis with age, dialysis vintage, history of cardiovascular disease (CVD) and parathyroid hormone levels. C-reactive protein levels did not correlate with OPG. Patients with clinical history of CVD had significantly higher OPG levels and OPG levels were positively correlated to PWV, an index of arterial stiffness. These associations were independent of age, sex, dialysis vintage, and diabetes. During the follow-up period, 40 deaths, including 25 cardiovascular deaths, were recorded. In crude analysis, each unit of increase in OPG was associated with increased all-cause (hazard ratios 1.14, 95% confidence interval 1.08-1.20) and CVD mortality (1.14 [1.07-1.21]), which persisted after adjustment for age, sex, dialysis vintage, diabetes, and baseline CVD (1.12 [1.05-1.19] and 1.11 [1.02-1.19], all-cause and CVD mortality, respectively). Conclusions: In long-term normoalbuminemic Japanese hemodialysis patients, with low prevalence of inflammation, OPG levels were strongly linked with both arterial stiffness and worse outcome. [ABSTRACT FROM AUTHOR]

Pre-adipocyte factor-1 (pref-1), originally identified in mouse 3T3-L1 pre-adipocytes, is known to play a key role in inhibiting the adipose conversion. As a first step to study the involvement of the PREF1 gene in intramuscular adipose tissue development in cattle, which has an economic importance for beef cattle, we have isolated the bovine PREF1 cDNA and genomic clones and characterized expression in abdominal adipose and promoter region of the bovine PREF1 gene. We have detected two bovine PREF1 splice-isoforms, PREF1C2 and PREF1A, in abdominal fat tissue. The RT-PCR experiment revealed that the two isoforms are identified in neonatal, but no in adult abdominal fat tissue, suggesting age-dependent suppression of the bovine PREF1 gene expression in the form of PREF1C2 and PREF1A in abdominal fat tissue. By mapping the regulatory region of this gene, we have shown that at least two regions within 1121 bp upstream of putative transcription start site are sufficient to confer promoter activity, when accompanied by a short region including the transcription start site. The chromosomal location of the PREF1 gene was determined by fluorescence in situ hybridization (FISH). The PREF1 gene locates on bovine chromosome 21q24. [ABSTRACT FROM AUTHOR]

Multiple etiologies of West syndrome have been reported; however, there are cases of unknown etiologies. Exposure to volatile organic compounds (VOCs) increases the risk of epilepsy; however, their effects on children remain unknown. This study aimed to investigate the association between maternal occupational usage of VOCs and West syndrome development in children. Using data from a cohort of 88,280 children, we extracted children born to mothers who had used VOCs during pregnancy. Based on an epilepsy diagnosis by the age of 2 years, the frequency of usage of VOCs was comparatively analyzed among the following groups: never diagnosed with epilepsy, West syndrome, and other epileptic syndromes. A total of 15, 154, and 88,111 children were categorized into the West syndrome, other epileptic syndrome, and never diagnosed with epilepsy groups, respectively. The odds ratio (OR) for West syndrome development increased with the frequency of permanent marker usage (one to three times a month: OR = 2.58, 95% confidence interval [CI] 0.75-8.90; one or more times a week: OR = 4.34, 95% CI 1.23-15.26). These results suggested an association between maternal occupational frequent usage of permanent marker and West syndrome development in children., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objectives: We investigated the long-term effectiveness, safety, and factors affecting Japanese Health Assessment Questionnaire (J-HAQ) improvement during abatacept treatment in Japanese rheumatoid arthritis (RA) patients., Methods: The Orencia® Registry in Geographically Assembled Multicenter Investigation (ORIGAMI) study is an ongoing observational study of biologic-naïve RA patients with moderate disease activity treated with subcutaneous abatacept (125 mg, once weekly). Patients treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) were extracted from the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) registry as a historical, weighted control group. The primary end point for this interim analysis was the proportion of patients with J-HAQ remission (score ≤0.5) at 3 years., Results: Among 279 abatacept-treated and 220 csDMARD-treated patients, J-HAQ remission was achieved at 3 years in 40.5% [95% confidence interval (CI) 34.7-46.2%] and 28.9% (95% CI 9.9-47.8%), respectively. Age, RA duration <1 year, baseline J-HAQ score, and Simplified Disease Activity Index remission at 6 months were associated with 3-year J-HAQ remission in the abatacept group. Overall, 24/298 patients (8.1%; safety analysis set) experienced serious adverse drug reactions with an incidence of 5.3 per 100 person-years., Conclusions: This study confirmed the 3-year effectiveness and safety and revealed potential factors associated with J-HAQ remission in biologic-naïve RA patients treated with abatacept in real-world clinical practice., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Background: This study aimed to investigate the potential association between the combination of low physical activity and low dietary diversity with mild cognitive impairment (MCI) in older Japanese adults., Methods: Data from 600 older adults (mean age, 74.1±6.4 years; women, 62.0%) were analyzed. We evaluated dietary variety based on the Food Frequency Score (FFS; maximum 30 points) by assessing the 1-week consumption frequencies of ten foods. An FFS of ≤16 indicated low dietary diversity. We assessed MCI using the National Center for Geriatrics and Gerontology Functional Assessment Tool. Physical activity levels was determined based on participant responses to two questions: "Do you engage in moderate levels of physical exercise or sports aimed at health?" and "Do you engage in low levels of physical exercise aimed at health?" Participants who responded "No" to both questions were classified as having low physical activity levels. We classified the participants into robust, low-dietary diversity, low-physical activity, and coexistence groups., Results: The overall prevalence of MCI was 20.7%, with rates in the robust, low dietary diversity, low physical activity, and coexistence groups of 17.7%, 24.7%, 25.0%, and 41.9%, respectively. Multiple logistic regression analysis revealed that low dietary diversity and physical activity were associated with MCI in older adults (odds ratio=2.80, 95% confidence interval 1.22-6.28)., Conclusion: The results of the present study demonstrated the association of the co-occurrence of low dietary diversity and low physical activity with MCI. Older adults with both risk factors may require early detection, as well as physical activity and dietary interventions.

This cross-sectional study examined the association of attachment with the frequency of dog walking and physical activity level among dog owners. We analyzed data collected in an internet survey conducted by the Japan Pet Food Association in 2023. Valid data were obtained from 1041 dog owners. The mean (SD) age of participants was 52.5 (14.9) years, with 57.5% being women. Ordinal logistic regression models showed that a higher attachment score was associated with a higher frequency of dog walking after controlling for important confounders (B = 0.04, SE = 0.02, p<0.01, Adjusted R2 = 0.03). Linear regression models showed that a higher attachment score was associated with a higher moderate-vigorous physical activity level (B = 1.43, SE = 0.44, p<0.01, Adjusted R2 = 0.01). These results suggest that dog owners with strong attachment maintain physical activity levels through caring for their dogs. Higher levels of physical activity might have protective effects against adverse health outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Taniguchi, Ikeuchi. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background/aim: For patients treated with osimertinib as first-line therapy, there have been no studies comparing both progression-free survival (PFS) and overall survival (OS) according to performance status (PS). Furthermore, no studies have examined differences in baseline genetic abnormalities between patients with poor and good PS. Therefore, we aimed to investigate differences in baseline genetic abnormalities and treatment effects between patients with poor and good PS who received osimertinib as the primary treatment., Patients and Methods: This is a secondary analysis of the ELUCIDATOR study, which is a multi-center prospective observational study in Japan that assessed mechanisms underlying resistance to osimertinib as first-line treatment for advanced non-small cell lung cancer with epidermal growth factor receptor mutations., Results: There were 153 and 25 patients in the good and poor PS groups, respectively. Multivariate analysis revealed no significant between-group differences in PFS (hazards ratio [HR]: 0.98, 95% confidence interval [CI]: 0.52-1.72, p = 0.946). Multivariate analysis of OS revealed that poor PS was a poor prognostic factor (HR: 2.67, 95% CI: 1.43-4.73, p = 0.003). Regarding baseline genetic abnormalities, there was a significant increase in APC-positive cases (20.0% vs. 2.2%, p = 0.009) and a trend toward more CTNNB1-positive cases in the poor PS group than in the good PS group (14.3% vs. 2.9%, p = 0.062)., Conclusion: There was no between-group difference in PFS, although OS was significantly inferior in the poor PS group. Additionally, there was a significant increase in APC-positive cases and a trend toward more CTNNB1-positive cases in the poor PS group., (© 2024. The Author(s).)

The 88 th Annual Scientific Meeting of the Japanese Circulation Society (JCS2024) was held from Friday, March 8 th to Sunday, March 10 th in Kobe, Japan. The main theme of this 3-day meeting was "The Future of Cardiology: Challenges in Overcoming Cardiovascular Disease". As COVID-19 has been finally conquered, with revision of its categorization under the Infectious Disease Control Law and relaxation of infection prevention measures, it was once again possible to have face-to-face presentations and lively discussion. JCS2024 was a major success, with 19,209 participants and attendees, thanks to the greatly appreciated cooperation and support from all affiliates.

The concept of pustulotic arthro-osteitis (PAO) was first reported by Sonozaki et al. in 1979, with diagnostic criteria (Sonozaki criteria) proposed in 1981. These criteria have served as the gold standard for PAO diagnosis for over 40 years. In recent years, there has been an increasing emphasis on maximizing the quality of life of patients with PAO. This is achieved by striving for clinical remission, structural remission, and functional remission through early diagnosis and appropriate therapeutic intervention from an early stage. This article is an English translation of a summary of the 'Modified PAO Diagnostic Guidance 2022', edited by the Japan Ministry of Health, Labour and Welfare's Research Group on improvement of medical standard and quality of life of patients with spondyloarthritis and related diseases represented by ankylosing spondylitis and the Japan Spondyloarthritis Society. This guidance is intended to be helpful to both Japanese and global communities in rheumatology and spondyloarthritis., (© Japan College of Rheumatology 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Background: Intra-articular platelet-rich plasma (PRP) injections have been proposed for the treatment of knee osteoarthritis (OA); however, their effectiveness in Japanese patients remains unclear., Purpose: To investigate whether 3 intra-articular injections of leukocyte-poor PRP (LP-PRP) improve symptoms and joint function in symptomatic Japanese patients with mild to moderate knee OA., Study Design: Randomized controlled trial; Level of evidence, 1., Methods: Of 72 patients screened, 30 were included and randomized to receive LP-PRP (n = 15) or saline (placebo; n = 15) injections between March 2019 and February 2023. Patients attended a screening visit and 3 treatment visits at 1 week apart, followed by 3 follow-up visits (at 4, 12, and 24 weeks) after the initial treatment visit. The primary efficacy outcome measure was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, whereas the secondary efficacy outcome measures were the proportion of patients showing a visual analog scale (VAS) improvement of ≥50%. Magnetic resonance imaging was performed to evaluate joint effusion and bone marrow lesions using the Whole-Organ Magnetic Resonance Imaging Score. Patients were followed for 24 weeks., Results: Patients in the PRP group (mean age, 65.9 years) had a mean hip-knee-ankle angle of 5.1°, with 7 and 8 patients demonstrating Kellgren-Lawrence grade 2 and 3 knee OA, respectively. Patients in the placebo group (mean age, 67.9 years) had a mean hip-knee-ankle angle of 3.8°, with 6 and 9 patients showing Kellgren-Lawrence grade 2 and 3 knee OA, respectively. No significant differences were identified in any baseline factors. The percentage change in Western Ontario and McMaster Universities Osteoarthritis Index scores from baseline to 24 weeks was significantly different (P= .032) between the PRP (median, 75.9%; quantile 1 [Q1], 49.6; quantile 3 [Q3], 94.1]) and placebo (median, 27.7%; Q1, -9.4; Q3, 80.9]) groups. Overall, 73.3% and 28.6% of the PRP group and placebo group, respectively, exhibited an improvement in visual analog scale scores of ≥50%, with a significant improvement observed in the PRP group ( P = .027). Changes in bone marrow lesions from baseline to 24 weeks, as assessed on magnetic resonance imaging, significantly differed between groups ( P = .017), with no significant differences in other secondary endpoints., Conclusion: In Japanese patients with knee OA, 3 intra-articular LP-PRP injections led to clinical improvements at 24-week follow-up and significant functional improvements and pain relief after 24 weeks., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This study was funded by a grant for the implementation of advanced medicine from the University of Tsukuba Hospital (No. TRM2019-06). AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Background: Suicide rates in Japan have increased during the COVID-19 pandemic, and foreign residents may be more vulnerable to mental stress during such crises. Therefore, we aimed to compare the trends in suicide rates during the COVID-19 pandemic between foreign residents and Japanese citizens., Methods: Vital statistics of Japan data from January 1, 2016 to December 31, 2021 were used to calculate quarterly sex-specific suicide rates for foreign residents and Japanese citizens. An event-study analysis was conducted to evaluate whether suicide rates during the COVID-19 pandemic increased compared to pre-pandemic estimates; foreign residents and Japanese citizens were compared using difference-in-difference-in-differences estimates., Results: Between 2016 and 2021, 1,431 foreign residents and 121,610 Japanese citizens died from suicide in Japan. Although the suicide rate for foreign residents was lower than that for Japanese citizens, Korean residents, who comprise approximately half of the foreign decedents, had largely higher suicide rates than Japanese citizens. The event-study analysis indicated that suicide rates increased among foreign residents for both men and women, and continued for men by the end of 2021. In Japanese citizens, after a decline in suicide rates in the second quarter of 2020, suicide rates increased both among men and women, and lasted for women until the fourth quarter of 2021. The difference-in-difference-in-differences analyses confirmed the initial decline in the second quarter of 2020 in suicide rate only in Japanese men and women, and the persistent increase through 2021 in foreign men., Conclusions: We found differential trends in suicide rates between foreign and Japanese men and women during the COVID-19 pandemic featuring a persistent increase in foreign men. Suicide prevention measures should be focused on these high-risk subpopulations., (© 2024. The Author(s).)

Objectives: To address improvements in quality of life, we analysed the relative contributions of factors to EuroQol 5 Dimensions (EQ-5D) in abatacept-treated rheumatoid arthritis patients in the Orencia® Registry in Geographically Assembled Multicenter Investigation (ORIGAMI) study., Methods: Patients who were evaluable for disease activity through to  Week 52 in the ORIGAMI study were divided into those achieving Simplified Disease Activity Index-remission/low disease activity (remission/LDA; n = 178) and patients with moderate disease activity/high disease activity (MDA/HDA; n = 99). We compared the changes in EQ-5D and other outcomes through to Week 52. Focusing on the remission/LDA group, the contribution of each factor to the variance of EQ-5D at baseline and Week 52 was examined using analysis of variance., Results: The remission/LDA group showed greater improvements than the MDA/HDA group in EQ-5D, Japanese Health Assessment Questionnaire, visual analogue scale for pain (Pain VAS), and patient's global assessment (PtGA). In the remission/LDA group, factors significantly contributing to EQ-5D were sex, C-reactive protein, and Pain VAS at baseline, and PtGA and age at Week 52., Conclusions: In rheumatoid arthritis patients who achieved remission/LDA during abatacept treatment, PtGA and age at Week 52 contribute to the variance of EQ-5D, suggesting that the identification of factors associated with PtGA may be important to address improvements in quality of life., (© Japan College of Rheumatology 2023. Published by Oxford University Press.)

Aims: Bleeding complications are often observed in patients with ST-segment elevation myocardial infarction (STEMI). Although the Japanese version of the high bleeding risk criteria (J-HBR) were established, it has not been sufficiently validated in patients with STEMI. This retrospective study aims to examine whether J-HBR is associated with cardiovascular and bleeding events in patients with STEMI., Methods: We included 897 patients with STEMI and divided them into the J-HBR group (n=567) and the non-J-HBR group (n=330). The primary endpoint was the major adverse cardiovascular events (MACE), defined as the composite of all-cause death, non-fatal myocardial infarction, ischemic stroke, and systemic embolism. Another primary endpoint was total bleeding events defined as type 3 or 5 bleeding events as defined by the Bleeding Academic Research Consortium ., Results: During the median follow-up duration of 573 days, 187 MACE and 141 total bleeding events were observed. The Kaplan-Meier curves showed that MACE and total bleeding events were more frequently observed in the J-HBR group than in the non-J-HBR group (p＜0.001). Multivariate Cox hazard analysis revealed that after controlling for multiple confounding factors, the J-HBR group was significantly associated with MACE (hazard ratio [HR] 4.676, 95% confidence interval (CI) 2.936-7.448, p＜0.001) and total bleeding events (HR 6.325, 95% CI 3.376-11.851, p＜0.001)., Conclusions: J-HBR is significantly associated with MACE and total bleeding events in patients with STEMI. This study validated J-HBR as a risk marker for bleeding events and suggests J-HBR as a potential risk marker for MACE in patients with STEMI.

Background: Catch-up growth issues among children born small for gestational age (SGA) present a substantial public health challenge. Prenatal exposure to heavy metals can cause adverse effects on birth weight. However, comprehensive studies on the accurate assessment of individual blood concentrations of heavy metals and their effect on the failure to achieve catch-up growth remain unavailable. This study aimed to evaluate the effects of uterine exposure to toxic metals cadmium, lead, and mercury and essential trace metals manganese and selenium at low concentrations on the postnatal growth of children born SGA., Methods: Data on newborn birth size and other factors were obtained from the medical record transcripts and self-administered questionnaires of participants in the Japan Environment and Children's Study. The blood concentrations of lead, cadmium, mercury, selenium, and manganese in pregnant women in their second or third trimester were determined by inductively coupled plasma mass spectrometry. These heavy metal concentrations were also assessed in pregnant women's cord blood. Furthermore, the relationship between each heavy metal and height measure/catch-up growth in SGA children aged 4 years was analyzed using linear and logistic regression methods. These models were adjusted for confounders., Results: We studied 4683 mother-child pairings from 103,060 pregnancies included in the Japan Environment and Children's Study. Of these, 278 pairs were also analyzed using cord blood. At 3 and 4 years old, 10.7% and 9.0% of children who were born below the 10th percentile of body weight had height standard deviation scores (SDSs) below 2, respectively. Cord blood cadmium concentrations were associated with the inability to catch up in growth by 3 or 4 years old and the height SDS at 3 years old. In maternal blood, only manganese was positively associated with the height SDS of SGA children aged 2 years; however, it was not significantly associated with catch-up growth in these children., Conclusion: Cadmium exposure is associated with failed catch-up development in SGA children. These new findings could help identify children highly at risk of failing to catch up in growth, and could motivate the elimination of heavy metal (especially cadmium) pollution to improve SGA children's growth., (© 2024. The Author(s).)

Background: Associated factors for frailty development according to age group remain unclear., Objectives: To identify frailty score trajectories among community-dwelling older Japanese individuals and examine their associated factors., Design: 13-year longitudinal study., Setting: Kusatsu Town in Gunma Prefecture, Japan., Participants: 1706 older adults aged ≥ 65 years who completed an annual frailty assessment at least once between 2007 and 2019., Measurements: Frailty status was determined using an index based on the Fried frailty phenotype criteria. Potential associated factors for frailty trajectory included physical, biological, lifestyle-related, and psychological factors, as well as comorbidities., Results: We identified five trajectory patterns in the frailty score from age of 65 to 90 years -individuals who were robust (Group 1, 10.5%) as well as individuals with late-onset frailty (Group 2, 16.1%), middle-onset frailty (Group 3, 25.6% and Group 4, 35.2%), and early-onset frailty (Group 5, 12.7%). Compared with the other groups, the early-onset group showed a higher prevalence of cerebrovascular diseases, bone and joint diseases, poor nutrition, sarcopenia, hospitalization, low cognitive function, and smoking at the end of follow-up. Associated factors in the middle-onset group largely overlapped with those of the early-onset group. The late-onset frailty group tended to have a higher association with heart disease and bone and joint diseases compared with the robust group., Conclusion: Our findings from a 13-year longitudinal study identified five frailty trajectory patterns and seven associated factors for frailty trajectory. Proposed effective population-based frailty prevention strategies in each age group may contribute to effective strategies to extend healthy life expectancy in aging, aged, and super-aged communities., Competing Interests: The authors have no potential conflicts of interest related to this research.

Objective: Concerns exist regarding the effects of maternal inhalation of household products on fetal health. This study aimed to clarify the impact of maternal exposure to household products, including spray formulations, on urological anomalies in offspring up to the age of 1 year., Methods: This study included data from 84 237 children from the Japan Environment and Children's Study, an ongoing nationwide cohort study. Using maternal self-report questionnaires, information on the use of organic solvents, waterproof sprays, insect-repellent sprays, insecticide sprays, and herbicides from implantation until the second or third trimester of pregnancy and data on urological anomalies were collected 1 year after delivery., Results: Urological anomalies occurred in 799 infants. Multivariate logistic regression analysis adjusted for maternal age, pregnancy body mass index, gestational diabetes, pre-existing maternal kidney disease, and preterm birth revealed no association between maternal exposure to organic solvents and the prevalence of offspring urological anomalies. Nevertheless, we observed significant associations between waterproof spray use during pregnancy and urological anomalies in boys (odds ratio [OR]: 1.28, 95% confidence interval [CI]: 1.03-1.59) and between the use of insecticide spray during pregnancy and urological anomalies in girls (OR: 1.48, 95% CI: 0.98-2.22). Sub-analysis revealed significant associations between waterproof spray use during pregnancy and vesicoureteral reflux in boys (OR: 2.14, 95% CI: 1.02-4.49) and between the use of insecticide spray during pregnancy and hydronephrosis in girls (OR: 2.23, 95% CI: 1.11-4.47)., Conclusion: Spray formulation use during pregnancy might increase the risk of urological anomalies in the offspring., (© 2023 The Japanese Urological Association.)

The sex of the conceived child is a significant concern for parents. To verify whether there women have pregnancy bias toward boys or girls, we investigated whether the history of continuous same-sex pregnancy was associated with the subsequent child's sex. We prospectively analyzed data from the Japan Environment and Children's Study, a birth cohort study. We included all cases of singleton live births (n = 98 412). Women with pregnancy due to infertility treatment were excluded (n = 6255); Similarly, women with a history of miscarriage, artificial abortion, stillbirth, and multiple pregnancies, and those with missing data on the sex of the previous child were excluded. Altogether, 62 718 women were included. For the first live birth, a male-biased sex ratio of 1.055 was observed. Further, no significant difference was found in the sex ratio of the conceived child between women with one boy and those with one girl previously. However, when there were more than two children previously, the subsequently conceived child's male/female sex ratio was significantly higher among boy-only mothers than among girl-only mothers. The results indicated that several pregnant women are biased toward conceiving either boys or girls., Competing Interests: Shuhei So is affiliated with the funded laboratory of Tawara IVF Clinic. Fumiko Tawara, Yu Taniguchi, and Naohiro Kanayama declare that they have no conflict of interest. The funder provided support in the form of salaries for authors [S.S]. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 So et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The Jomon period of Japan is characterised by a unique combination of sedentary and hunting/gathering lifestyles, spanning for more than 10,000 years from the final Pleistocene to the Holocene. The transition from the preceding Palaeolithic period to the Jomon period is known to have begun with the appearance of pottery usage. However, knowledge of the genetic background of the Jomon people is still limited., Aim: We aimed to determine the population-scale complete mitogenome sequences of the Initial Jomon human remains and compare the occurrence of mitochondrial haplogroups in the Jomon period from temporal and regional perspectives., Subjects and Methods: For human remains dated to 8200-8600 cal BP, we determined their complete mitogenome sequences using target enrichment-coupled next-generation sequencing., Results: We successfully obtained the complete mitogenome sequences with high depth of coverage and high concordance on consensus sequences. These sequences differed by more than three bases each, except for two individuals having completely identical sequences. Co-existence of individuals with haplogroups N9b and M7a was first observed at the same archaeological site from the Initial Jomon period., Conclusion: The genetic diversity within the population was not found to be low even in the Initial Jomon period.

This longitudinal study aimed to compare 1-year mortality between users of home- and community-based services (HCBS) and residential facilities (nursing homes, group homes, and geriatric apartments) among non-hospitalized frail older adults in Japan. Using three nationwide data sources, we conducted a nationwide pooled cohort study of 1-year follow-up among certified users of long-term care insurance (LTCI) aged  65 years and older from 2007 through 2016 to compare 1-year mortality using a logistic regression model. Overall, compared to HCBS users, mortality was higher in residents in nursing homes and geriatric apartments but lower in group home residents. While mortality gradually increased over time among those in residential facilities, it remained at a level similar to that of HCBS users. Since 2006, Japan's public health policy has been to increase end-of-life care in residential facilities. Our results indicate that this policy resulted in an increase in mortality in residential facilities, possibly due to accommodation of more severely ill people there, or a shift in their focus from transferring dying residents to hospitals to preserve the dignity of residents., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Aim: To examine the relationship between the number of present and functional teeth at baseline and future incidence of loss of independence., Methods: Participants were community-dwelling older individuals who participated in a comprehensive geriatric health examination conducted in Kusatsu town, Japan, between 2009 and 2015. The primary endpoint was the incidence of loss of independence among participants, defined as the first certification of long-term care insurance in Japan. The numbers of present and functional teeth at baseline were determined via an oral examination. Demographics, clinical variables (e.g., history of chronic diseases and psychosocial factors), blood nutritional markers, physical functions, and perceived masticatory function were assessed., Results: This study included 1121 individuals, and 205 individuals suffered from loss of independence during the follow-up period. Kaplan-Meier estimates of loss of independence for participants with smaller numbers of present and functional teeth were significantly greater than for those with larger numbers of teeth. Cox proportional hazard analyses indicated that a smaller number of present teeth was not a significant risk factor after adjusting for demographic characteristics. However, the number of functional teeth was a significant risk factor after the adjustment (hazard ratio: 1.975 [1.168-3.340]). Additionally, higher hazard ratios were observed in other adjusted models, but they were not statistically significant., Conclusions: The number of functional teeth may be more closely related to the future incidence of loss of independence than the number of present teeth. This novel finding suggests that prosthodontic rehabilitation for tooth loss possibly prevents the future incidence of this life-event. Geriatr Gerontol Int 2022; 22: 1032-1039., (© 2022 The Authors. Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.)

Background: To our knowledge, the association of maternal exposure to metallic elements with weight trajectory pattern from the neonatal period has not been investigated., Objectives: The goals of this study were to identify infant growth trajectories in weight in the first 3 y of life and to determine the associations of maternal blood levels of lead, cadmium, mercury, selenium, and manganese with growth trajectory., Methods: This longitudinal study, part of the Japan Environment and Children Study, enrolled 103,099 pregnant women at 15 Regional Centres across Japan between 2011 and 2014. Lead, cadmium, mercury, selenium, and manganese levels were measured in blood samples collected in the second (14-27 wk gestational age) or third trimester ( ≥ 28 wk ). Growth trajectory of 99,014 children was followed until age 3 y. Raw weight values were transformed to age- and sex-specific weight standard deviation (SD) scores, and latent-class group-based trajectory models were estimated to determine weight trajectories. Associations between maternal metallic element levels and weight trajectory were examined using multinomial logistic regression models after confounder adjustment., Results: We identified 5 trajectory patterns based on weight SD score: 4.74% of infants were classified in Group I, very small to small; 31.26% in Group II, moderately small; 21.91% in Group III, moderately small to moderately large; 28.06% in Group IV, moderately large to normal; and 14.03% in Group V, moderately large to large. On multinomial logistic regression, higher maternal lead and selenium levels tended to be associated with increased odds ratios (ORs) of poor weight SD score trajectories (Groups I and II), in comparison with Group III. Higher levels of mercury were associated with decreased ORs, whereas higher levels of manganese were associated with increased ORs of "moderately large" trajectories (Groups IV and V)., Discussion: Maternal lead, mercury, selenium, and manganese blood levels affect infant growth trajectory pattern in the first 3 y of life. https://doi.org/10.1289/EHP10321.

We conducted two-year seroprevalence surveys of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies among outpatients and healthcare workers (HCWs) at Ehime University Hospital. Data were collected for outpatients and HCWs in June 2020 (1st survey), December 2020 (2nd survey), July 2021 (3rd survey), and December 2021 (4th survey), focusing on demographics, occupation, and the seroprevalence of anti-SARS-CoV-2 antibodies. Blood samples were obtained from randomly selected outpatients who visited our hospital for medical care and HCWs undergoing regular medical checks with opt-out informed consent. SARS-CoV-2 antibody positivity was evaluated using two laboratory-based quantitative tests. The total number of participants enrolled was 6,369 (1st survey: 1,000 outpatients and 743 HCWs, 2nd survey: 1,000 outpatients and 407 HCWs, 3rd survey: 1,000 outpatients and 804 HCWs, 4th survey: 1,000 outpatients and 415 HCWs). The prevalence of SARS-CoV-2 antibodies among outpatients and HCWs was 0-0.1% and 0-0.124% during the research period, respectively, and changed little over time. These findings suggest that the magnitude of COVID-19 infection during the pandemic among outpatients and HCWs in this rural hospital might have been small.

Compared with the relatively well-investigated effects of childhood exposure to lead on neurocognitive deficits, those of prenatal exposure remain relatively inconclusive. We aimed to investigate the association between prenatal blood lead levels and neurodevelopmental delay during the first three years of life. From a prospective cohort of the Japan Environment and Children's Study, we analyzed a total of 80,759 children. The exposure factors were prenatal lead concentrations measured from maternal whole blood in the second/third trimesters and umbilical cord blood at birth. Neurodevelopment was assessed at 6, 12, 18, 24, 30, and 36 months old using a screening tool, the Ages and Stages Questionnaires, third edition (ASQ). The outcome measures were any suspected neurodevelopmental delay (sNDD) identified via the ASQ during the first (sNDD-1Y), second (sNDD-2Y), and third (sNDD-3Y) years of life. sNDD-1Y, 2Y, and 3Y were identified in 18.0%, 16.2%, and 17.2% of children, respectively. The geometric means of blood lead concentration in this study were much lower (0.62 μg/dL in maternal blood and 0.50 μg/dL in cord blood) than previously investigated levels. Multivariable regression models revealed that there were no associations between maternal blood lead and sNDD-1Y and 2Y and between cord blood lead and sNDD-1Y, 2Y, and 3Y. Although a higher maternal blood lead was associated with a reduced risk of sNDD-3Y (adjusted relative risk: 0.84, 95% confidence interval 0.75-0.94, per 1 increase in common logarithm of lead concentration), there were no dose-response relationships in the analysis using quintiles of lead concentrations. Using a large-scale data set, the present study demonstrated no convincing evidence for an inverse association between levels of prenatal blood lead and neurodevelopment in early childhood. Longitudinal measurements of prenatal and postnatal lead levels are needed to understand the relationship between lead exposure and neurocognitive development., (© 2022. The Author(s).)

Objectives　The national database for long-term care insurance (LTCI) of Japan (Kaigo DB) enables researchers to access comprehensive data from its LTCI registry, eligibility assessment records, claims for service usage, and information about service providers. However, studies regarding the death or mortality of beneficiaries cannot be conducted because Kaigo DB does not contain death records, and researchers are not allowed to link Kaigo DB to other databases, such as national death records. Therefore, we aimed to assess the validity of using an insurer's disqualification from an LTCI beneficiary as a proxy of death.Methods　We used 510,751,798 monthly beneficiary records between April 2007 and March 2017 from the LTCI registry, while excluding data for ineligible persons for LTCI benefit or those younger than 65 years. We identified insurer cases disqualified from LTCI beneficiaries and linked them to national death records using deterministic linkage methods by dates of birth and death, sex, and residence. We considered the cases as positive if they were disqualified and their record was linked to a death. We used sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) as validity indices.Results　We identified 5,986,991 (1.17%) disqualified and 5,295,961 death cases. Sensitivity, specificity, PPV, and NPV of disqualification for death were 100%, 99.86%, 88.46%, and 100%, respectively. After stratification, PPV of disqualification was between 85% and 88% before 2012, 91% after 2012, 91.9% in men, and 85.9% in women. PPV increased with age (65-69 years: 80.6%, 70-74 years: 86.7%, 75-79 years: 86.4%, 80-84 years: 86.7%, 85-89 years: 88.0%, 90-94 years: 90.6%, and 95+ years: 93.4%) and level of care needed (support level: 72.2%, care level (CL) 1: 79.7%, CL2: 85.9%, CL3: 89.3%, CL4: 92.3%, and CL5: 94.0%).Conclusions　Disqualification from the LTCI registry is an inappropriate measure to estimate mortality accurately because it has a 10% false-positive rate. However, it appears sufficiently valid to use disqualification as a proxy outcome of death, although the main effect or confounding of a possible predictor of death could be slightly underestimated.

Background: Real-world evidence on the preference for and effectiveness of third- or later-line (3L +) monotherapy for HER2-positive gastric cancer is limited in Japan. This study evaluated the utility of nivolumab, irinotecan, and trifluridine/tipiracil (FTD/TPI) monotherapy as 3L + treatment in Japanese patients with HER2-positive gastric/gastroesophageal junction (G/GEJ) cancer who were previously treated with trastuzumab., Methods: In this multicenter, retrospective, observational study (20 centers), data of eligible patients were extracted from medical records (September 22, 2017-March 31, 2020), with follow-up until June 30, 2020. Outcomes included overall survival (OS), real-world progression-free survival (rwPFS), time to treatment failure (TTF), objective response rate (ORR; complete response [CR] + partial response [PR]), and disease control rate (DCR)., Results: Of 127 enrolled patients, the overall analysis population comprised 117 patients (median [range] age, 71 [38-89] years). The most commonly prescribed 3L + monotherapy was nivolumab (n = 100), followed by irinotecan (n = 12) and FTD/TPI (n = 5). The median (95% confidence interval [CI]) OS, rwPFS, and TTF were 6.2 (4.5-8.0), 1.9 (1.5-2.3), and 1.8 (1.5-2.2) months, respectively, at median (range) 150 (25-1007) days of follow-up. The ORR (CR + PR) and DCR were 9.0% (1% + 8%) and 32.0%, respectively. Factors such as higher neutrophil-lymphocyte ratio (≥ 2.54), Glasgow prognostic score (≥ 1), Eastern Cooperative Oncology Group performance status (ECOG PS; ≥ 2), and hepatic metastasis significantly impacted OS., Conclusions: The observed OS in this study for HER2-positive G/GEJ cancer was shorter than that reported previously, suggesting that the effectiveness of nivolumab, irinotecan, or FTD/TPI as 3L + therapy may be limited., (© 2022. The Author(s).)

Background: Growth restriction in the prenatal period is a significant public health concern. Metals can negatively affect birth size, and pregnant women may be exposed to metal mixtures. Comprehensive studies analyzing the effects of combined metal exposure with accurate individual blood metal concentrations are limited. The current study investigated the associations between maternal metal exposure and birth size in a large, nationwide Japanese cohort using individual and mixed model approaches., Methods: Lead, cadmium, mercury, selenium, and manganese blood concentrations were measured in pregnant women in the Japan Environment and Children's Study (JECS). Measurements of infant birth size-including body weight, body length, and head and chest circumference-were collected. Linear and logistic regressions were used for birth size measurements and the odds of an infant being small in size for gestational age, respectively. Associations between combined metal mixtures and measurements at birth were evaluated using quantile g-computation and Bayesian kernel machine regression (BKMR)., Results: Of the 103,060 JECS pregnancies, 93,739 mother-infant pairs were analyzed. The linear regression models showed that lead, selenium, cadmium, and manganese-but not mercury-were associated with body weight. Cadmium was associated with length and chest circumference and mercury was associated with head circumference. Quantile g-computation revealed that manganese increased infant birth weight, length, head circumference, and chest circumference. Lead was the strongest negative factor for infant birth weight, length, head circumference, and chest circumference. The BKMR analysis revealed that the metals had an additive, rather than a synergistic effect., Conclusion: Metal exposure is associated with infant birth size, with lead and manganese playing a more significant role in Japan. The effects of prenatal combined metal exposure at low levels warrant public health attention., (Copyright © 2022. Published by Elsevier Ltd.)

Purpose: The coagulation activation leads to thrombotic complications such as venous thromboembolism (VTE) in patients with coronavirus disease-2019 (COVID-19). Prophylactic anticoagulation therapy has been recommended for hospitalized COVID-19 patients in clinical guidelines. This retrospective cohort study aimed to examine the association between pre-admission anticoagulation treatment and three outcomes: in-hospital death, VTE, and major bleeding among hospitalized COVID-19 patients in Japan., Methods: Using a large-scale claims database built by the Medical Data Vision Co. in Japan, we identified patients hospitalized for COVID-19 who had outpatient prescription data at least once within 3 months before being hospitalized. Exposure was set as pre-admission anticoagulation treatment (direct oral anticoagulant or vitamin K antagonist), and outcomes were in-hospital death, VTE, and major bleeding. We conducted multivariable logistic regression analyses, adjusting for a single summarized score (a propensity score of receiving pre-admission anticoagulation) for VTE and major bleeding, due to the small number of outcomes., Results: Among the 2612 analytic patients, 179 (6.9%) had pre-admission anticoagulation. Crude incidence proportions were 13.4% versus 8.5% for in-hospital death, 0.56% versus 0.58% for VTE, and 2.2% versus 1.1% for major bleeding among patients with and without pre-admission anticoagulation, respectively. Adjusted odds ratios (95% confidence intervals) were 1.25 (0.75-2.08) for in-hospital death, 0.21 (0.02-1.97) for VTE, and 2.63 (0.80-8.65) for major bleeding. Several sensitivity analyses did not change the results., Conclusions: We found no evidence that pre-admission anticoagulation treatment was associated with in-hospital death. However, a larger sample size may be needed to conclude its effect on VTE and major bleeding., (© 2022 John Wiley & Sons Ltd.)

Background: The Japan Environment and Children's Study (JECS) is a nationwide birth cohort study investigating environmental effects on children's health and development. A Sub-Cohort Study has begun, conducting extended exposure and outcome measurements by targeting a subgroup randomly selected from the JECS Main Study. We report the Sub-Cohort Study methodology and participants' baseline profiles., Methods: Of 100,148 children in the JECS Main Study, children born after April 1, 2013 who met eligibility criteria ([1] all questionnaire and medical record data from children and their mothers collected from the first trimester to 6 months of age, [2] biospecimens [except umbilical cord blood] from children and their mothers collected at first to second/third trimester and delivery) were randomly selected for each Regional Centre at regular intervals. Face-to-face assessment of neuropsychiatric development, body measurement, paediatrician's examination, blood/urine collection for clinical testing and chemical analysis, and home visits (ambient and indoor air measurement and dust collection) are conducted. Participants are followed up at 1.5 and 3 years old for home visits, and 2, 4, 6, and 8 years old for developmental/medical examination. The details of protocols after age 10 are under discussion., Results: Of 10,302 selected children, 5,017 participated. The profiles of the participating mothers, fathers and children did not substantially differ between the Main Study and Sub-Cohort Study., Conclusion: The JECS Sub-Cohort Study offers a platform for investigating associations between environmental exposure and outcomes.

Aim: To investigate whether the type and frequency of social interaction during the state of emergency due to coronavirus disease were associated with self-rated health (SRH) after the state of emergency., Methods: Data from a cross-sectional study were collected for 889 oldest-old adults in Bibai City, Hokkaido, Japan. In total, 612 participants (mean age: 83.0 ± 4.3 years; women: 51.8%) were included in the analysis, taking biological sex into account. The self-reported questionnaire included questions about demographic variables, SRH (July 2020, after the emergency), and the type and frequency of social interaction (March 2020, during the state of emergency)., Results: There was no significant association between social interaction and SRH in men (P > 0.05). Women who had social interactions (both face-to-face and non-face-to-face) more than once a week during the state of emergency reported higher SRH after the emergency than those who did not (odds ratio 2.17, 95% confidence interval 1.07-4.41)., Conclusions: Having both types of interaction more than once a week during the state of emergency was related to higher SRH after the emergency among oldest-old women. It is suggested that having opportunities for both types of interaction at least once a week would potentially be beneficial for high SRH in women, even in situations where the declaration of a state of emergency restricts face-to-face interaction. Geriatr Gerontol Int 2022; 22: 405-411., (© 2022 Japan Geriatrics Society.)

Background: Sarcopenia-related parameters may have differential impacts on health-related outcomes in older adults. We examined dose-response relationships of body composition, muscle strength, and physical performance with incident disability and mortality., Methods: This prospective study included 1765 Japanese residents (862 men; 903 women) aged ≥65 years who participated in health check-ups. Outcomes were incident disability and all-cause mortality. Fat mass index (FMI) and skeletal muscle mass index (SMI), determined using segmental multi-frequency bioelectrical impedance analysis, handgrip strength (HGS), and usual gait speed (UGS) were measured. We determined multivariate-adjusted hazard ratios (HRs) for disability and mortality relative to sex-specific reference values (FMI: medians; SMI: 7.0 kg/m 2 for men and 5.7 kg/m 2 for women; HGS: 28 kg for men and 18 kg for women; or UGS: 1.0 m/s for both sexes). Association shapes were examined using restricted cubic splines or fractional polynomial functions., Results: The median follow-up was 5.3 years; 107 (12.7%) men and 123 (14.2%) women developed disability, and 101 (11.7%) men and 56 (6.2%) women died. FMI did not impact any outcome in men and disability in women, while an FMI ≤ 7.3 kg/m 2 (median) was significantly associated with higher mortality risk in women, compared with median FMI. SMI did not impact disability in either sex and mortality in women, but showed a significant inverse dose-response relationship with mortality risk in men [HRs (95% confidence intervals) of minimum and maximum values compared with the reference value: 2.18 (1.07-4.46) and 0.43 (0.20-0.93), respectively], independent of HGS and UGS. HGS and UGS showed a significant inverse dose-response relationship with disability in both sexes [HGS: 1.71 (1.00-2.91) and 0.31 (0.09-0.99), respectively, in men, 2.42 (1.18-4.96) and 0.41 (0.20-0.85), respectively, in women; UGS: 2.14 (1.23-3.74) and 0.23 (0.08-0.67), respectively, in men, 3.26 (2.07-5.14) and 0.11 (0.05-0.26), respectively, in women] and mortality in women [HGS: 6.84 (2.84-16.47) and 0.06 (0.02-0.21), respectively; UGS: 2.67 (1.14-6.27) and 0.30 (0.11-0.85), respectively], independent of body composition, but did not impact mortality in men., Conclusions: Disability risk was more dependent on muscle strength and physical performance in both sexes. Mortality risk in men was more dependent on muscle mass, and mortality risk in women was influenced by lower fat mass along with muscle strength and physical performance. Although improving muscle strength and physical performance should be the first target for health promotion, it is also necessary to pay attention to body composition to extend life expectancy in older adults., (© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Background: The Japan Environment and Children's Study (JECS) is a nationwide birth cohort study of environmental factors affecting children's health and development. We summarize the complete blood count and chemistry panel statistical data from pregnant women enrolled in JECS., Methods: Statistical data of up to 58,056 mother's sample in their first (gestational age ≤ 13 weeks) and second trimester (22-27 weeks) were calculated., Results: Mean (SD) values in the first trimester were: white blood cell count, 7866 (1906)/μL; red blood cell count, 417 (33) 10 4 /μL; hemoglobin, 12.4 (1.0) g/dL; hematocrit, 37.1 (2.6)%; mean corpuscular volume, 89.2 (4.7) fL; mean corpuscular hemoglobin, 29.8 (1.9) pg; mean corpuscular hemoglobin concentration, 33.3 (0.9)%; platelet count, 24.8 (5.2) 10 4 /μL; HbA1c, 5.26 (0.26)%; total cholesterol, 181 (28) mg/dL; low density lipoprotein cholesterol, 95 (23) mg/dL; high density lipoprotein cholesterol, 73 (13) mg/dL; free cholesterol, 41 (7) mg/dL; triglycerides, 109 (47) mg/dL; total protein, 6.9 (0.4) g/dL; and albumin, 4.1 (0.2) g/dL. Mean values (SD) in the second trimester were: total cholesterol, 246 (38) mg/dL; free cholesterol, 61 (9) mg/dL; triglycerides, 183 (70) mg/dL; total protein, 6.5 (0.4) g/dL; and albumin, 3.6 (0.2) g/dL., Conclusions: These data will be useful for future JECS studies.

Objectives: This study examined the association between dog and cat ownership, the onset of disability and all-cause mortality in an older population. Dog and cat owners take more regular exercise and have closer social relationships than non-owners. We further assess the beneficial effects of these moderating variables on the onset of disability and mortality., Methods: Dog and cat ownership data were collected from 11233 community-dwelling adults age 65 years and older. These data were matched with data about the onset of disability held by the Japanese long-term care insurance system. Local registry data were used to ascertain all-cause mortality., Results: During the approximately 3.5 year follow-up period, 17.1% of the sample suffered onset of disability, and 5.2% died. Logistic regression analysis indicated that, compared with a reference group of those who had never owned a dog (odds ratio fixed at 1.0), older adults who were currently dog owners had a significantly lower odds ratio of onset of disability (OR = 0.54 95% CI: 0.37-0.79). Our results further show that regular exercise interacts with dog ownership to reduce the risk of disability. The association of dog and/or cat ownership with all-cause mortality was not statistically significant., Conclusions: Dog ownership appears to protect against incident disability among older Japanese adults. Additional benefits are gained from ownership combined with regular exercise. Daily dog care may have an important role to play in health promotion and successful aging., Competing Interests: The authors have declared that no competing interests exist.

Background/aim: Systemic inflammation responses have been associated with cancer development, progression and metastasis. Little is known about the risk of metastasis based on inflammatory-based scores in patients with osteosarcoma., Patients and Methods: A total of 65 osteosarcoma patients without metastasis at presentation were enrolled in this retrospective study. All had been diagnosed histologically, and their laboratory data at the first visit were collected from medical records. The inflammation-based scores, tumor size, location, staging, pathological fracture, treatment methods, follow-up periods, and metastasis-free duration were evaluated., Results: A multivariate Cox regression analysis revealed that a high platelet-lymphocyte ratio (PLR) >116 [hazard ratio (HR)=3.8, 95% confidence interval =1.5-9.3; p<0.01], and neutrophil count (NC) ≤4,030/μl (HR=4.5, 95%CI=1.7-12.3; p<0.01), were independent risk factors significantly associated with metastasis of osteosarcoma patients., Conclusion: The combination of a high PLR >116 and NC ≤4,030/μl before treatment was a useful inflammatory-based prognostic indicator for metastasis in patients with osteosarcoma., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Otitis media (OM) is common among young children and is related to hearing loss. We investigated the association between maternal insecticide use, from conception to the first and second/third trimesters, and OM events in children in the first year of age. Data from Japan Environment and Children's Study were used in this prospective cohort study. Characteristics of patients with and without history of OM during the first year of age were compared. The association between history of OM in the first year and insecticide use was evaluated using logistic regression analysis. The study enrolled 98,255 infants. There was no significant difference in the frequency of insecticide use between groups. Insecticide use of more than once a week from conception to the first trimester significantly increased the occurrence of OM in children in the first year (odds ratio [OR] = 1.30, 95% confidence interval [CI] 1.01-1.67). The association between OM in the first year and insecticide use from conception to the first trimester was only significant in the group without daycare attendance (OR 1.76, 95% CI 1.30-2.38). Maternal insecticide use more than once a week from conception to the first trimester significantly increased OM risk in offspring without daycare attendance., (© 2022. The Author(s).)

Objectives: The gap between the numbers of organ donors and recipients is a common problem worldwide. This study was designed to investigate the importance of 'individual readiness', a here introduced novel concept in transplantation medicine and a measure of positive attitudes towards organ donation and transplantation., Design: A cross-sectional online survey was used to collect the research data., Participants: The participants were recruited by a Japanese research company and affiliates in South Korea and Taiwan and fulfilled the following criteria: (1) laypersons aged 18-75 years, (2) residents of the countries and (3) understood the questions in their native languages., Primary Outcome Measures: The survey investigated the interest and attitude of individuals regarding transplantation medicine by asking multiple choice questions. Based on answers concerning attitude, a positive group was identified as willing to be organ donors and recipients, and a non-positive group was identified as unwilling to be donors and recipients. The ratio between the positive and non-positive group, the P/N ratio, was introduced as an index of individual readiness., Results: 1500 samples were included in this analysis. Individuals with interest agreed more with statements on organ donation than those without interest, and the P/N ratio per country was compatible with the actual deceased organ donors rate per million population (ADODR)., Conclusions: Interest in transplantation medicine was associated with positive attitudes, and positive attitudes were associated with a higher ADODR. These results support that individual readiness is an important determinant for the number of donors. The P/N ratio can be used as an index to assess individual readiness in organ transplantation, at least in countries with minor to moderate popularisation. Further studies of individual readiness using the P/N ratio should be undertaken to develop policies and initiatives for increasing organ donations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: The provision of in-home and community end-of-life care has emerged as an important policy issue for aging populations around the world. Despite most patients expressing the wish to die at home (as opposed to in the hospital), substantial geographic variation persists in the prevalence of in-home death at the end of life., Objective: To assess the association of municipal characteristics with variation in the place of death among care-dependent older people in Japan., Design, Setting, and Participants: In this cross-sectional study using multilevel logistic regression, analyses were performed using national claims data under Japan's long-term care insurance system. The study population included long-term care insurance beneficiaries 65 years and older who died in 2015, excluding those who died from external causes, such as unintentional injuries. Data analyses were conducted from January 1 to April 31, 2021., Exposures: Predisposing, enabling, and need factors at the individual and municipal levels according to a behavioral model., Main Outcomes and Measures: The outcome was whether individuals died at home or not., Results: This cross-sectional study analyzed 544 836 decedents (median [IQR] age, 87 [81-91] years; 300 142 [55.1%] female). The proportion of in-home deaths was 10.3%. In the multilevel null model, 7.2% of the variance in the place of death was associated with municipal-level characteristics. Municipal characteristics were associated with more of the variance than were prefectural characteristics (2.7%). The largest proportional change (7.3%) in variance at the municipality level was observed when enabling factors (ie, medical and long-term care resources) were added to the model. Municipalities with a high proportion of in-home death were more likely to have a higher supply of clinics, physicians, and care workers providing in-home services per population, as well as a lower number of hospital beds and long-term care facility workers per population., Conclusions and Relevance: In this cross-sectional study, municipal characteristics explained a substantial proportion of the geographic variance in in-home death in Japan. These results suggest that municipal policy makers need to ensure an adequate supply of clinics, physicians, and care workers providing in-home services to meet the preferences of care-dependent older people who wish to spend their final days at home.

Background: Japan has promoted end-of-life care at home and in long-term care facilities, and the total proportion of in-hospital deaths has decreased recently. However, the difference in trends of in-hospital deaths by the cause of death remains unclear. We investigated the variation in trends of in-hospital deaths among older adults with long-term care from 2007 to 2017, by cause of death and place of care., Methods: Using the national long-term care insurance registry, long-term care claims data, and national death records, we identified people aged 65 years or older who died between 2007 and 2017 and used long-term care services in the month before death. Using a joinpoint regression model, we evaluated time trends of the proportion of in-hospital deaths by cause of death (cancer, heart diseases, cerebrovascular diseases, pneumonia, and senility) and place of care (home, long-term care health facility, or long-term care welfare facility)., Results: Of the 3,261,839 participants, the mean age was 87.0 ± 8.0 years, and 59.2% were female. Overall, the proportion of in-hospital deaths decreased from 66.2% in 2007 to 55.3% in 2017. By cause of death, the proportion of in-hospital deaths remained the highest for pneumonia (81.6% in 2007 and 77.2% in 2017) and lowest for senility (25.5% in 2007 and 20.0% in 2017) in all types of places of care. The joinpoint regression analysis showed the steepest decline among those who died of senility, especially among long-term care health facility residents., Conclusions: The findings of this nationwide study suggest that there was a decreasing trend of in-hospital deaths among older adults, although the speed of decline and absolute values varied widely depending on the cause of death and place of care., (© 2021. The Author(s).)

Background: The coronavirus disease 2019 (COVID-19) pandemic has had a widespread significant impact on mental health. However, the effect of providing care to family members (informal caregiving) on changes in mental health status during the pandemic remains unclear., Methods: Using cross-sectional data from a large internet survey conducted between August and September 2020, we investigated the association of informal caregiving status with the incidence of mental health deterioration (increased loneliness, self-reported deterioration in mental health, and new suicidal ideation) in Japan during the COVID-19 pandemic., Results: Among 25,482 participants (mean age 48.8 [standard deviation 17.3]; 50.3% women), 2,500 (9.8%) were providing informal care during the pandemic. After adjusting for potential confounders, informal caregivers were more likely than non-caregivers to experience increased loneliness (adjusted odds ratio [aOR] 2.16; 95% confidence interval [CI] 1.70-2.76), self-reported deterioration in mental health (aOR 1.54; 95% CI 1.14-2.08), and new incidence of suicidal ideation (aOR 3.65; 95% CI 1.92-6.92). The degree of mental health deterioration depended on the intensity of care. For example, the incidence rates of new suicidal ideation were 15.0%, 5.2%, and 3.6% for individuals who provided high-intensity caregiving, those who provided low-intensity caregiving, and non-caregivers, respectively (p-for-trend<0.001). The stratified analysis by gender showed that informal caregiving was associated with self-reported deterioration in mental health status among women (aOR 2.19; 95% CI 1.49-3.21) but not men (aOR 1.08; 95% CI 0.75-1.56)., Conclusion: Informal caregivers were more likely to experience mental health deterioration than non-caregivers during the COVID-19 pandemic., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Methylmercury concentrations in Minamata Bay are high, but the cause is unclear. We conducted a basic study on the behavior of methylmercury in Minamata Bay seawater; the findings suggest that mercury methylation may occur throughout the year in Minamata Bay. Seawater temperature, salinity, and concentrations of dissolved organic carbon were the environmental factors that affected methylation, and the degree of methylation was closely related to bacterial community structure. The concentration of methylmercury in suspended particulate matter was highest 10 m below the surface and decreased with greater depths. We did not observe a correlation between methylmercury concentrations in suspended particulate matter and concentrations of dissolved methylmercury., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: Despite the significant utilization of long-term care (LTC) services at the end of life, evidence on the trajectory of LTC expenditure in later life is scarce. This study aims to identify distinct trajectories of LTC expenditure in the last 5 years of life and to examine whether these trajectories differ according to cause of death., Design: A nationwide retrospective longitudinal cohort study based on linked data of National LTC Claims and the Japan's National Vital Statistic., Setting and Participants: Participants comprised decedents aged 70 years or older and who died in 2017., Methods: We assessed 5 years of monthly LTC expenditure among participants and applied group-based trajectory model to identify distinct trajectories of LTC expenditure. Subsequently multinominal logistic regression analysis was performed to investigate how these trajectories vary according to cause of death., Results: Among 1,124,335 decedents, 4 distinct trajectories of LTC expenditure were identified: persistently low (58.5%), late increase (9.8%), progressive increase then late decrease (8.8%), and persistently high (22.9%). Approximately 80.7% of total LTC expenditure was spent by the persistently high group. After adjustment for age and sex; deaths due to age-related physical debility and dementia were associated with persistently high LTC expenditure., Conclusions and Implications: Ongoing discussions of LTC policy and reducing LTC expenditure may be more effective when emphasizing persistently high spenders. In addition, budget allocation for LTC at the end of life should be combined with data for health conditions., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Prenatal cadmium exposure has been associated with adverse neurodevelopmental outcomes. However, previous findings are contradictory, and little is known about the potential modifiers of the cadmium-related neurodevelopmental risk. We investigated the associations between prenatal cadmium exposure and neurodevelopment in 2-year-old children and examined the influence of mother/child characteristics., Methods: We recruited 3545 mother-child pairs from the Japan Environment and Children's Study. We collected maternal blood during mid/late pregnancy and cord blood at delivery, and measured cadmium concentrations using inductively coupled plasma mass spectrometry. Neurodevelopment was assessed using the Kyoto Scale of Psychological Development (KSPD), which includes cognitive-adaptive (C-A), language-social (L-S), postural-motor (P-M) and developmental quotient (DQ) domains. Associations between cadmium and KSPD scores were tested using multivariable models after controlling for confounders., Results: Median levels (interquartile ranges) of cadmium in maternal and cord blood were 0.70 (0.52-0.95) and 0.04 (0.03-0.06) μg/L, respectively. Maternal blood cadmium concentrations were inversely associated with P-M scores in boys (β = -1.4, 95% confidence interval (CI): -2.7, -0.038), DQ in children of mothers who smoked during pregnancy (β = -2.9, 95% CI: -5.7, -0.12), P-M (β = -5.4, 95% CI: -10, -0.67), C-A (β = -6.1, 95% CI: -11, -1.8), L-S (β = -9.0, 95% CI: -13, -4.8) and DQ scores (β = -6.4, 95% CI: -9.6, -3.1) in children born to mothers with gestational diabetes. Cord blood cadmium concentrations were negatively associated with L-S scores (β = -6.0., 95% CI: -11, -0.91) in children born to mothers with gestational diabetes., Conclusions: Prenatal cadmium exposure was negatively associated with neurodevelopment in boys, in children whose mothers smoked, and in children born to mothers with gestational diabetes. Further studies in other populations are needed to confirm our findings., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Wheezing is a common symptom in infants, which may occasionally develop into asthma. There are many factors related to infant wheezing, including anatomical features, viral infections, and passive smoking. There are only a few reports on the association between renovation and pregnancy worldwide, and reports on this association are inadequate in Japan. This study aimed to examine the association between house renovation and new construction during pregnancy and wheezing in infants during the first year of life using data from the Japan Environment and Children's Study (JECS)., Methods: Data of pregnant women registered in JECS were collected using self-administered questionnaires during the second/third trimester and 1 month after delivery. Childbirth records were completed by the doctors. Similarly, wheezing in infants was evaluated using self-administered questionnaires 1 year after birth. Logistic regression analysis was used to determine the primary outcome., Results: In total, 75,731 infants, excluding those with unknown gender, who were not singleton infants, and who relocated during pregnancy and the first month of life, were examined in this study. Renovation during pregnancy increased the prevalence of wheezing (odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.20-1.48) and recurrent wheezing (OR: 1.22, 95% CI: 1.00-1.48) in the first year of life. The relationship between new construction during pregnancy and wheezing in infants was insignificant (OR: 0.98, 95% CI: 0.90-1.06)., Conclusions: Renovation during pregnancy may be a risk factor for wheezing in infants, and should be avoided., (Copyright © 2021 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: The relationship between allergic individuals and their responsiveness to routine vaccines has rarely been investigated. This study examined whether the seroprevalence of measles antibody differed between children with and without allergic diseases in the general pediatric population., Methods: The cross-sectional study was performed within a prospective general birth cohort (a pilot study of the Japan Environment & Children's Pilot Study [JECS]) of children aged 8 years. The clinical history of allergic diseases, measles, and the concentration of measles immunoglobulin G titers in serum enzyme immunoassay were examined. Fisher's exact tests were used to assess the relationships between the allergic characteristics of the children and their measles antibody positivity rates., Results: This study included 162 children. Any allergic disease was reported in 75 (46.3%). The measles antibody positivity rate was 94.7% among children with any allergic diseases and 92.0% among children without allergic diseases. Our results revealed no differences in measles antibody seropositivity between children with allergies and controls., Conclusions: Children with allergies mount and maintain a comparable immune response to the measles vaccine., Competing Interests: The authors have declared that no competing interests exist.

Toxoplasma gondii is a globally wide-spread parasite that infects almost all species of mammals and birds, including humans. We studied the spatial distribution of individual T. gondii-seropositive wild boar in Gifu Prefecture (10,621 km 2 ), Japan. Altogether, 744 wild boars were captured at 663 points around human settlements in Gifu Prefecture. Serum samples were collected after recording the exact capture locations, along with each wild boar's body length and sex. We then used a commercial enzyme-linked immunosorbent assay kit for swine to measure anti-T. gondii antibodies in these animals. Among the 744 wild boars, 169 tested positive for T. gondii (22.7%). No significant difference in T. gondii seroprevalence was observed between the mountainous northern region with high winter snow cover and the mild-wintered geographical plain of the southern part of the prefecture. In contrast, 8 of the 11 wild boars that were captured in a public park surrounded by residential areas showed T. gondii seropositivity (72.7%), a value significantly higher than those of the wild boar populations in the other prefecture areas. This in-depth analysis, which spans the big city suburbs and rural areas of a whole prefecture, explains the seroprevalence of zoonotic T. gondii in wild boar and has public health implications., (© 2021. The Author(s).)