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Background: In Japan, postgraduate clinical training encompasses a 2-year residency program, including at least 24 weeks of internal medicine (IM) rotations. However, the fragmented structure of these rotations can compromise the training's quality and depth. For example, a resident might spend only a few weeks in cardiology before moving to endocrinology, without sufficient time to deepen their understanding or have clinical experience. This study examined current patterns and lengths of IM rotations within the Japanese postgraduate medical system. It scrutinized the piecemeal approach—whereby residents may engage in multiple short-term stints across various subspecialties without an overarching, integrated experience—and explored potential consequences for their clinical education. Methods: This nationwide, multicenter, cross-sectional study used data from self-reported questionnaires completed by participants in the 2022 General Medicine In-Training Examination (GM-ITE). Data of 1,393 postgraduate year (PGY) one and two resident physicians who participated in the GM-ITE were included. We examined the IM rotation duration and number of IM subspecialties chosen by resident physicians during a 2-year rotation. Results: Approximately half of the participants chose IM rotation periods of 32–40 weeks. A significant proportion of participants rotated in 5–7 internal medicine departments throughout the observation period. Notable variations in the distribution of rotations were observed, characterized by a common pattern where resident physicians typically spend 4 weeks in each department before moving to the next. This 4-week rotation is incrementally repeated across different subspecialties without a longer, continuous period in any single area. Notably, 39.7% of participants did not undertake general internal medicine rotations. These results suggest a narrowed exposure to medical conditions and patient care practices. Conclusions: Our study highlights the need to address the fragmented structure of IM rotations in Japan. We suggest that short, specialized learning periods may limit the opportunity to gain broad in-depth knowledge and practical experience. To improve the efficacy of postgraduate clinical education, we recommend fostering more sustained and comprehensive learning experiences. [ABSTRACT FROM AUTHOR]

This article examines the impact of working‐hour restrictions on the well‐being, performance, and education of medical residents in Japan. Despite Japan's plan to introduce new regulations for resident working hours by 2024, there is still an ongoing debate regarding their appropriateness. This review provides a comprehensive overview of the current regulations of resident working hours worldwide, with a specific focus on weekly hours. The varying regulations are highlighted, including the 80‐hour‐per‐week regulation in the United States and the 48‐h‐per‐week regulation in the European Union influencing other regions. The article also discusses the effectiveness of working‐hour restrictions on residents' mental health, with shorter working hours having potentially greater benefits. However, the impacts on medical safety and resident education are mixed, and further reduction in working hours must be carefully considered to avoid adverse effects. The planned changes to working‐hour limits for residents in Japan offer a unique opportunity to gain new evidence on the impact of such regulations, which will be of interest to policymakers and researchers worldwide. [ABSTRACT FROM AUTHOR]

Background: Crowned dens syndrome (CDS) is characterized by calcification around the odontoid process, accompanied by neck pain. Although CDS is supposedly rare, we regularly diagnose and manage this condition, indicating a perception gap between previous studies and our experience. The purpose of this study was to determine the annual incidence of CDS, time to diagnosis in CDS, as well as the features of CDS. Methods: The study design was a retrospective case series study conducted at eight teaching hospitals in Japan. We identified CDS cases from April 2013–March 2015. CDS was diagnosed when patients had acute onset of neck pain and CT showed calcification around the dens and when other diagnoses were unlikely. Results: Seventy‐two CDS cases were identified. Mean annual incidence was 4.6 ± 2.3 cases at each hospital. Among those with available data, 57 of 64 had limited rotation (89.1%). The diagnosis of CDS was made in general internal medicine or the emergency medicine department in 61 cases (84.7%). A total of 62 cases (86.1%) were diagnosed within 1 day of presentation, and the median time from initial presentation at the hospital to diagnosis was 0.0 days (25th–75th percentiles, 0.0–1.0). For treatment, NSAIDs were used in 56cases (77.8%) and acetaminophen in 20 cases (27.8%). Conclusion: CDS might be more common than has been reported to date. Time to diagnosis of CDS was within 1 day of visiting a teaching hospital. Cervical motion restriction is common in CDS and may be useful in establishing the diagnosis. [ABSTRACT FROM AUTHOR]

Background: The effect of duty hour (DH) restrictions on postgraduate residents' acquisition of clinical competencies is unclear. We evaluated the relationship between DHs and competency‐related knowledge acquisition using the General Medicine In‐training Examination (GM‐ITE). Methods: We conducted a multicenter, cross‐sectional study of community hospital residents among 2019 GM‐ITE examinees. Self‐reported average DHs per week were classified into five DH categories and the competency domains were classified into four areas: symptomatology and clinical reasoning (CR), physical examination and clinical procedure (PP), medical interview and professionalism (MP), and disease knowledge (DK). The association between these scores and DHs was examined using random‐intercept linear models with and without adjustment for confounding factors. Results: We included 4753 participants in the analyses. Of these, 31% were women, and 49.1% were in the postgraduate year (PGY) 2. Mean CR and MP scores were lower among residents in Category 1 (<50 h) than in residents in Category 3 (≥60 and <70 h; reference group). Mean DK scores were lower among residents in Categories 1 and 2 (≥50 and <60 h) than in the reference group. PGY‐2 residents in Categories 1 and 2 had lower CR scores than those in Category 3; however, PGY‐1 residents in Category 5 showed higher scores. Conclusions: The relationship between DHs and each competency area is not strictly linear. The acquisition of knowledge of physical examination and clinical procedures skills in particular may not be related to DHs. [ABSTRACT FROM AUTHOR]

Inchinkoto (ICKT), a traditional herbal medicine that is often used as a hepatoprotective drug in Japan, has pharmacological properties that include antioxidant, anti-inflammatory, and choleretic actions. Genipin is a metabolite of geniposide and the most abundant ingredient of ICKT; furthermore, it is considered to be the active substance responsible for its pharmacological properties in the liver. Drugs with such pharmacological characteristics are expected to prevent intestinal barrier dysfunction, which causes inflammatory bowel diseases (IBDs). However, no studies have investigated the effects of ICKT on the intestinal epithelial barrier. Therefore, we investigated the activity of ICKT in intestinal tight junctions by using cultured Caco-2 cell monolayers. The action of the compound on tight junctions was examined by measuring transepithelial electrical resistance (TEER) and sodium fluorescein (Na-F) permeability in the presence or absence of lipopolysaccharide (LPS). Moreover, the expression of the tight junction protein claudin-1 was assessed by using immunofluorescent staining. ICKT and genipin increased TEER and decreased Na-F permeability, which was suggestive of enhanced intestinal epithelial barrier function. Moreover, they prevented the LPS-induced destruction of the barrier, i.e., a decrease in TEER and an increase in Na-F permeability. Immunofluorescence staining revealed a high claudin-1 expression level on the cell surface, whereas exposure to LPS downregulated claudin-1. In turn, ICKT and genipin prevented the LPS-mediated reduction of claudin-1. These results suggest that ICKT enhances intestinal epithelial barrier function by upregulating claudin-1. Furthermore, genipin contributed to these effects. ICKT may be a promising medicine for the prevention and treatment of diseases associated with intestinal barrier disruption, such as IBD, obesity, and metabolic disorders. [ABSTRACT FROM AUTHOR]

Background: Burnout is a psychological syndrome consisting of emotional exhaustion, cynicism, and decreased professional efficacy. The Maslach Burnout Inventory (MBI) is widely used as the standard measure. However, the MBI is lengthy and not free to use, which makes it a less than ideal tool for regularly assessing burnout. The single question burnout measure (SMB) is a novel and simple measure of burnout, which is associated well with emotional exhaustion and has sufficient diagnostic performance for burnout. This study aimed to evaluate the concurrent and convergent validity of the Japanese version of the single‐item measure of burnout (SMB‐J) compared with the MBI. Methods: Ninety‐four medical residents volunteered to complete the MBI‐General Survey (MBI‐GS) and the SMB‐J. We assessed the concurrent (sensitivity and specificity) and convergent validity of the SMB‐J compared with the MBI‐GS. Results: The sensitivity for identifying burnout using the SMB‐J was 53.8%, and the specificity was 88.2%. The area under the receiver operating characteristic curve (AUC) was 0.71. MBI‐GS scores on the subscales of Emotional Exhaustion (r = 0.509, p < 0.0001) and Cynicism (r = 0.57, p < 0.0001) strongly correlated with the SMB‐J scores. Conclusions: We concluded that for identifying burnout among Japanese medical residents, the psychometric properties of the SMB‐J are comparable to those of the original version of the SMB. Although the SMB‐J has low sensitivity to detect burnout, it is more convenient to use than the MBI. [ABSTRACT FROM AUTHOR]

The new duty hour (DH) limit for doctors in Japan will begin in 2024, setting the maximum DHs for postgraduate residents at approximately 80 h weekly. To set appropriate limits, understanding the association between DHs and psychological health is necessary. Thus, we assessed the relationship between residents' psychological health and DHs. We conducted a cross-sectional study involving examinees of the General Medicine In-training Examination 2020. Mental health outcomes were measured dichotomously using the Patient Health Questionnaire-2 for depression and Mini-Z 2.0, for burnout, stress, and satisfaction. Weekly DHs were measured in seven categories at 10-h intervals. The prevalence ratios (PRs) between the DH categories were estimated for each outcome. Of the 6045 residents who provided data on DHs and psychological outcomes, 37.3% showed signs of depression, 21.6% experienced burn out, and 39.2% were highly stressed. In contrast, 62.3% were highly satisfied with their training. Proportions of burnout were higher among residents in Category 6 (≥ 90 and < 100 h; PR 1.36; 95% CI 1.11–1.66) and Category 7 (≥ 100 h; PR 1.36; 95% CI 1.10–1.68) compared with residents in Category 3 (≥ 60 and < 70 h; reference). The results partially support the weekly 80-h DH limit in terms of resident well-being. [ABSTRACT FROM AUTHOR]

The relationship between duty hours (DH) and the performance of postgraduate residents is needed to establish appropriate DH limits. This study explores their relationship using the General Medicine In-training Examination (GM-ITE). In this cross-sectional study, GM-ITE examinees of 2019 had participated. We analyzed data from the examination and questionnaire, including DH per week (eight categories). We examined the association between DH and GM-ITE score, using random-intercept linear models with and without adjustments. Five thousand five hundred and ninety-three participants (50.7% PGY-1, 31.6% female, 10.0% university hospitals) were included. Mean GM-ITE scores were lower among residents in Category 2 (45–50 h; mean score difference, −1.05; p < 0.001) and Category 4 (55–60 h; −0.63; p = 0.008) compared with residents in Category 5 (60–65 h; Reference). PGY-2 residents in Categories 2–4 had lower GM-ITE scores compared to those in Category 5. University residents in Category 1 and Category 5 showed a large mean difference (−3.43; p = 0.01). DH <60–65 h per week was independently associated with lower resident performance, but more DH did not improve performance. DH of 60–65 h per week may be the optimal balance for a resident's education and well-being. [ABSTRACT FROM AUTHOR]

Purpose: In Japan, the General Medicine In-training Examination (GM-ITE) was developed by a non-profit organization in 2012. The GM-ITE aimed to assess the general clinical knowledge among residents and to improve the training programs; however, it has not been sufficiently validated and is not used for high-stake decision-making. This study examined the association between GM-ITE and another test measure, the Professional and Linguistic Assessments Board (PLAB) 1 examination. Methods: Ninety-seven residents who completed the GM-ITE in fiscal year 2019 were recruited and took the PLAB 1 examination in Japanese. The association between two tests was assessed using the Pearson product-moment statistics. The discrimination indexes were also assessed for each question. Results: A total of 91 residents at 17 teaching hospitals were finally included in the analysis, of whom 69 (75.8%) were women and 59 (64.8%) were postgraduate second year residents. All the participants were affiliated with community hospitals. Positive correlations were demonstrated between the GM-ITE and the PLAB scores (r = 0.58, p < 0.001). The correlations between the PLAB score and the scores in GM-ITE categories were as follows: symptomatology/clinical reasoning (r = 0.54, p < 0.001), physical examination/procedure (r = 0.38, p < 0.001), medical interview/professionalism (r = 0.25, p < 0.001), and disease knowledge (r = 0.36, p < 0.001). The mean discrimination index of each question of the GM-ITE (mean ± SD; 0.23 ± 0.15) was higher than that of the PLAB (0.16 ± 0.16; p = 0.004). Conclusion: This study demonstrates incremental validity evidence of the GM-ITE to assess the clinical knowledge acquisition. The results indicate that GM-ITE can be widely used to improve resident education in Japan. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization has set a goal of hepatitis C virus (HCV) elimination by the year 2030. However, no regions in Japan have succeeded in eradicating HCV. Micro-elimination is an approach to attain hepatitis C eradication in which national eradication goals are applied to specific populations so that viral treatment and control efforts can move forward quickly and efficiently. In order to eradicate HCV from Japan, this study aims to achieve HCV micro-elimination in the town of Nagawa. Methods and design: The Nagawa Project is an ongoing, prospective, multiple-institution, observational study running from April 1, 2021, to March 31, 2024. All residents of Nagawa town, excluding those under 20 years of age, not consenting to the study, or unable to undergo health check-ups due to nursing care needs, will be included. If found to be HCV antibody-positive, the participant will be recommended to see a doctor in consideration of MAC-2 binding protein glycosylation isomer values. Then, the participant will undergo serum HCV RNA measurement with the real-time polymerase chain reaction by an attending physician. If the participant is HCV RNA-positive, he or she will be referred to a hepatologist for further evaluation. In the case of a definitive diagnosis of chronic hepatitis C, direct acting antiviral treatment will be initiated. Through this process, HCV will be systematically micro-eliminated from the region. Discussion: The Nagawa Project will reveal the prevalence of chronic HCV in addition to the HCV eradication rate in Nagawa town towards achieving HCV micro-elimination. Trial registration: This study is performed by Shinshu University School of Medicine and was registered as UMIN 000044114 on May 6, 2021. [ABSTRACT FROM AUTHOR]

Agricultural weeds are the most important biotic constraints to global crop production, and chief among these is weedy rice. Despite increasing yield losses from weedy rice in recent years worldwide, the genetic basis of weediness evolution remains unclear. Using whole-genome sequence analyses, we examined the origins and adaptation of Japanese weedy rice. We find evidence for a weed origin from tropical japonica crop ancestry, which has not previously been documented in surveys of weedy rice worldwide. We further show that adaptation occurs largely through different genetic mechanisms between independently-evolved temperate japonica- and tropical japonica-derived strains; most genomic signatures of positive selection are unique within weed types. In addition, some weedy rice strains have evolved through hybridization between weedy and cultivated rice with adaptive introgression from the crop. Surprisingly, introgression from cultivated rice confers not only crop-like adaptive traits (such as shorter plant height, facilitating crop mimicry) but also weedy-like traits (such as seed dormancy). These findings reveal how hybridization with cultivated rice can promote persistence and proliferation of weedy rice. Imaizumi et al. examine the origin and evolution of Japanese weedy rice and document the role of hybridization in weedy rice origins. Their results show that there is parallel evolution in rice feralization, and document the temperate and tropical japonica origins of weedy rice in Japan. [ABSTRACT FROM AUTHOR]

Simple Summary: Natural killer (NK) cells normally respond to tumor cells and virally infected cells by killing them via the innate immune system. However, the functional impairment of NK cells has been observed in hepatocellular carcinoma. The NK-cell phenotype is partially mediated through the binding of killer cell immunoglobulin-like receptors (KIR) with human leukocyte antigen (HLA) class I ligands. This study evaluated the involvement of KIR–HLA pairs in hepatocellular carcinoma development in 211 patients with hepatitis C virus-associated cirrhosis. HLA-Bw4 and the KIR3DL1+HLA-Bw4 pair were significantly associated with hepatocellular carcinoma onset during a median follow-up of 6.6 years, which suggested that functional interactions between KIR and HLA or HLA-Bw4 may influence the risk of cancer development. Natural killer cells are partially mediated through the binding of killer cell immunoglobulin-like receptors (KIR) with human leukocyte antigen (HLA) class I ligands. This investigation examined the risk of hepatocellular carcinoma (HCC) in relation to KIR–HLA pairs in patients with compensated hepatitis C virus (HCV)-associated cirrhosis. A total of 211 Japanese compensated HCV cirrhotic cases were retrospectively enrolled. After KIR, HLA-A, HLA-Bw, and HLA-C typing, associations between HLA, KIR, and KIR–HLA combinations and HCC development were evaluated using the Cox proportional hazards model with the stepwise method. During a median follow-up period of 6.6 years, 69.7% of patients exhibited HCC. The proportions of HLA-Bw4 and the KIR3DL1 + HLA-Bw4 pair were significantly higher in patients with HCC than in those without (78.9% vs. 64.1%; odds ratio (OR)—2.10, 95% confidence interval (CI)—1.10–4.01; p = 0.023 and 76.2% vs. 60.9%, odds ratio—2.05, p = 0.024, respectively). Multivariate analysis revealed the factors of male gender (hazard ratio (HR)—1.56, 95% CI—1.12–2.17; p = 0.009), α-fetoprotein > 5.6 ng/mL (HR—1.56, 95% CI—1.10–2.10; p = 0.011), and KIR3DL1 + HLA-Bw4 (HR—1.69, 95% CI—1.15–2.48; p = 0.007) as independent risk factors for developing HCC. Furthermore, the cumulative incidence of HCC was significantly higher in patients with KIR3DL1 + HLA-Bw4 than in those without (log-rank test; p = 0.013). The above findings suggest KIR3DL1 + HLA-Bw4, in addition to HLA-Bw4, as a novel KIR–HLA pair possibly associated with HCC development in HCV cirrhosis. HCV-associated cirrhotic patients with the risk factors of male gender, α-fetoprotein > 5.6 ng/mL, and KIR3DL1 + HLA-Bw4 may require careful surveillance for HCC onset. [ABSTRACT FROM AUTHOR]

Background: The relationship between educational outcomes and the use of web-based clinical knowledge support systems in teaching hospitals remains unknown in Japan. A previous study on this topic could have been affected by recall bias because of the use of a self-reported questionnaire., Objective: We aimed to explore the relationship between the use of the Wolters Kluwer UpToDate clinical knowledge support system in teaching hospitals and residents' General Medicine In-Training Examination (GM-ITE) scores. In this study, we objectively evaluated the relationship between the total number of UpToDate hospital use logs and the GM-ITE scores., Methods: This nationwide cross-sectional study included postgraduate year-1 and -2 residents who had taken the examination in the 2020 academic year. Hospital-level information was obtained from published web pages, and UpToDate hospital use logs were provided by Wolters Kluwer. We evaluated the relationship between the total number of UpToDate hospital use logs and residents' GM-ITE scores. We analyzed 215 teaching hospitals with at least 5 GM-ITE examinees and hospital use logs from 2017 to 2019., Results: The study population consisted of 3013 residents from 215 teaching hospitals with at least 5 GM-ITE examinees and web-based resource use log data from 2017 to 2019. High-use hospital residents had significantly higher GM-ITE scores than low-use hospital residents (mean 26.9, SD 2.0 vs mean 26.2, SD 2.3; P=.009; Cohen d=0.35, 95% CI 0.08-0.62). The GM-ITE scores were significantly correlated with the total number of hospital use logs (Pearson r=0.28; P<.001). The multilevel analysis revealed a positive association between the total number of logs divided by the number of hospital physicians and the GM-ITE scores (estimated coefficient=0.36, 95% CI 0.14-0.59; P=.001)., Conclusions: The findings suggest that the development of residents' clinical reasoning abilities through UpToDate is associated with high GM-ITE scores. Thus, higher use of UpToDate may lead physicians and residents in high-use hospitals to increase the implementation of evidence-based medicine, leading to high educational outcomes., (© Koshi Kataoka, Yuji Nishizaki, Taro Shimizu, Yu Yamamoto, Kiyoshi Shikino, Masanori Nojima, Kazuya Nagasaki, Sho Fukui, Sho Nishiguchi, Kohta Katayama, Masaru Kurihara, Rieko Ueda, Hiroyuki Kobayashi, Yasuharu Tokuda. Originally published in JMIR Medical Education (https://mededu.jmir.org).)

Long duty hours (DH) impair sleep and negatively affect residents' health and medical safety. This cross-sectional study investigated the association among residents' DH, sleep duration, insomnia, sleep impairment, depressive symptoms, and self-reported medical errors among 5579 residents in Japan who completed the General Medicine In-Training Examination (2021) and participated in the training-environment survey. Weekly DH was classified under seven categories. Sleep duration and insomnia symptoms, from the Athens Insomnia Scale, were analysed to determine sleep impairment; depressive symptoms and medical errors were self-reported. Among 5095 residents, 15.5% slept < 5 h/day, and 26.7% had insomnia. In multivariable analysis, compared with ≥ 60 and < 70, DH ≥ 90 h/week associated with shorter sleep duration and worsen insomnia symptoms. Shorter durations of sleep and more intense symptoms of insomnia were associated with increased depressive symptoms. Medical errors increased only among residents with insomnia, but were not associated with sleep duration. DH > 90 h/week could lead to shorter sleep duration, worsen insomnia symptoms, and negatively impact well-being and medical safety. There was no significant association between sleep duration and medical errors; however, insomnia conferred an increased risk of medical errors. Limiting DH for residents to avoid excessive workload can help improve resident sleep, enhance resident well-being, and potentially reduce insomnia-associated medical errors., (© 2024. The Author(s).)

Wastewater-based epidemiology is expected to be able to identify SARS-CoV-2 variants at an early stage via next-generation sequencing. In the present study, we developed a highly sensitive amplicon sequencing method targeting the spike gene of SARS-CoV-2, which allows for sequencing viral genomes from wastewater containing a low amount of virus. Primers were designed to amplify a relatively long region (599 bp) around the receptor-binding domain in the SARS-CoV-2 spike gene, which could distinguish initial major variants of concern. To validate the methodology, we retrospectively analyzed wastewater samples collected from a septic tank installed in a COVID-19 quarantine facility between October and December 2020. The relative abundance of D614G mutant in SARS-CoV-2 genomes in the facility wastewater increased from 47.5 % to 83.1 % during the study period. The N501Y mutant, which is the characteristic mutation of the Alpha-like strain, was detected from wastewater collected on December 24, 2020, which agreed with the fact that a patient infected with the Alpha-like strain was quarantined in the facility on this date. We then analyzed archived municipal wastewater samples collected between November 2020 and January 2021 that contained low SARS-CoV-2 concentrations ranging from 0.23 to 0.43 copies/qPCR reaction (corresponding to 3.30 to 4.15 log 10 copies/L). The targeted amplicon sequencing revealed that the Alpha-like variant with D614G and N501Y mutations was present in municipal wastewater collected on December 4, 2020 and later, suggesting that the variant had already spread in the community before its first clinical confirmation in Japan on December 25, 2020. These results demonstrate that targeted amplicon sequencing of wastewater samples is a powerful surveillance tool applicable to low COVID-19 prevalence periods and may contribute to the early detection of emerging variants., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Masaaki Kitajima reports financial support was provided by Shionogi and Co Ltd. Masaaki Kitajima reports financial support was provided by AdvanSentinel Inc. Ryo Iwamoto reports writing assistance was provided by Editage. Satoshi Okabe reports financial support was provided by Shionogi and Co Ltd. Satoshi Okabe reports financial support was provided by AdvanSentinel Inc. Ryo Iwamoto, Ken-ichi Setsukinai, and Hiroyuki Kobayashi are employees of Shionogi & Co., Ltd., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: The relationship between the care of patients with COVID-19 and mental health among resident physicians in Japan is imperative for ensuring appropriate care of patients with COVID-19 and should be clarified. We herein assessed the relationship between the care of patients with COVID-19 and mental health among postgraduate year 1 (PGY-1) and PGY-2 resident physicians and factors associated with mental health., Design: This nationwide cross-sectional study analysed data obtained using the clinical training environment self-reported questionnaire., Setting: An observational study across Japan among resident physicians (PGY-1 and PGY-2) from 583 teaching hospitals., Participants: Examinees who took the general medicine in-training examination of academic year 2020., Primary and Secondary Outcome Measures: The Patient Health Questionnaire and Mini-Z 2.0 were used to assess mental health, and experience of caring for patients with COVID-19 was divided into three groups (none, 1-10 and ≥11). The prevalence of mental conditions in the three groups was compared using the 'modified' Poisson generalised estimating equations by adjusting for prefecture-level, hospital-level and resident-level variables., Results: Of the 5976 participants analysed, 50.9% were PGY-1. The prevalence of burnout was 21.4%. Moreover, 47.0% of all resident physicians had no experience in the care of patients with COVID-19. The well-experienced group accounted for only 7.9% of the total participants. A positive association was found between the number of caring patients with COVID-19 and burnout (prevalence ratio 1.25; 95% CI 1.02 to 1.53). Moreover, the shortage of personal protective equipment was identified as a major contributor to burnout (prevalence ratio 1.60; 95% CI 1.36 to 1.88)., Conclusions: Resident physicians who experienced more care of patients with COVID-19 had slightly greater burnout prevalence than those who did not. Approximately half of resident physicians did not participate in the care of patients with COVID-19, which posed a challenge from an educational perspective., Competing Interests: Competing interests: YN received an honorarium from JAMEP as a GM-ITE project manager. YT is the JAMEP director, and he received an honorarium from JAMEP as a speaker of the JAMEP lecture. TShinozaki received an honorarium from JAMEP as a statistical adviser. HK and KS received an honorarium from JAMEP as speakers of the JAMEP lecture. TShimizu, YY, KS and SF received an honorarium from JAMEP as exam preparers of GM-ITE., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to be present in sewage, and wastewater-based epidemiology has attracted much attention. However, the physical partitioning of SARS-CoV-2 in wastewater and the removal efficiency of treatment systems require further investigation. This study aimed to investigate the detectability and physical partitioning of SARS-CoV-2 in wastewater and assess its removal in a large-scale septic tank employing anaerobic, anoxic, and oxic processes in a sequential batch reactor, which was installed in a coronavirus disease 2019 (COVID-19) quarantine facility. The amount of SARS-CoV-2 RNA in wastewater was determined with polyethylene glycol (PEG) precipitation followed by quantitative polymerase chain reaction (qPCR), and the association of SARS-CoV-2 with wastewater solids was evaluated by the effect of filtration prior to PEG precipitation (pre-filtration). The amount of SARS-CoV-2 RNA detected from pre-filtered samples was substantially lower than that of samples without pre-filtration. These results suggest that most SARS-CoV-2 particles in wastewater are associated with the suspended solids excluded by pre-filtration. The removal efficiency of SARS-CoV-2 in the septic tank was evaluated based on the SARS-CoV-2 RNA concentrations in untreated and treated wastewater, which was determined by the detection method optimized in this study. Escherichia coli and pepper mild mottle virus (PMMoV) were also quantified to validate the wastewater treatment system's performance. The mean log 10 reduction values of SARS-CoV-2, E. coli, and PMMoV were 2.47 (range, 2.25-2.68), 2.81 (range, 2.45-3.18), and 0.66 (range, 0.61-0.70), respectively, demonstrating that SARS-CoV-2 removal by the wastewater treatment system was comparable to or better than the removal of fecal indicators. These results suggest that SARS-CoV-2 can be readily removed by the septic tank. This is the first study to determine the removal efficiency of SARS-CoV-2 in a facility-level sequencing batch activated sludge system., Competing Interests: Declaration of competing interest Ryo Iwamoto, Ken-ichi Setsukinai, and Hiroyuki Kobayashi are employees of Shionogi & Co., Ltd. Masaaki Kitajima received research funding and patent royalties from Shionogi & Co., Ltd. Satoshi Okabe received research funding from Shionogi & Co., Ltd. Kiyoshi Yamaguchi, Chisato Arakawa, Hiroki Ando, Eiji Haramoto, Kotoe Katayama, Takuya Yamagishi, Sumire Sorano, Michio Murakami, Shigeru Kyuwa, and Seiya Imoto have no competing interests to declare., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

This study aimed to evaluate the association between locomotive syndrome (LS) and daily physical activity (PA) in community-dwelling older adults. This cross-sectional study included 80 healthy Japanese older adults (40 men and 40 women; age: 60-79 years). Habitual daily PA was evaluated using a triaxial wrist accelerometer. Participants were divided into two groups based on the results of the two-step test, stand-up test, and 25-question geriatric locomotive function scale. Binomial logistic regression analysis was conducted to examine the statistical relationships between daily PA and category of LS, adjusting for age from adjusted odds ratio (adjusted OR) with the 95 percent confidence intervals (95%CI) and bootstrap 95%CI. The mean step count and time spent on moderate to vigorous physical activity (MVPA) were significantly higher among non-LS participants than among LS participants in women, but not in men. Logistic regression analyses indicated that spending longer than 28 min/day on MVPA was significantly associated with a lower likelihood of LS relative to short time category under 28 min/day in women (adjusted OR = 0.12, 95%CI = 0.02-0.59, bootstrap 95%CI = 0.01-0.43), but not in men. This study suggests that in community-dwelling older women, those with higher MVPA had lower odds of LS, and daily MVPA was associated with LS, but not in men. Therefore, the associations between LS and daily physical activity were partly dependent on sex differences.

Background and Purpose: The prevalence of anxiety in patients with chronic constipation is particularly high and these individuals are not necessarily satisfied by normal treatments targeting the gastrointestinal tract. Kamikihito, a traditional Japanese Kampo medicine, has been widely used to date in treating anxiety and neurosis in Japan. We conducted a single-arm, open-label pilot study of female patients with intractable chronic constipation and anxiety who took kamikihito by mouth for 12 weeks., Materials and Methods: Validated symptom questionnaires on anxiety and gastrointestinal symptoms [the Profile of Mood States, second edition (POMS2); the State-Trait Anxiety Inventory (STAI); and the Gastrointestinal Symptom Rating Scale (GSRS)] were completed at each study visit. Plasma, salivary, and stool samples were also assessed to evaluate levels of clinical bioactive substances linked to stress and inflammation, oxidative levels, the metabolome profile, and gut microbiota., Results: Twenty-four patients completed this study. Anxiety was significantly reduced at four and 12 weeks (Tension-Anxiety subscale of the POMS2, p = 0.006 and p = 0.039; Trait anxiety score of the STAI, p < 0.001 and p = 0.034), while the total GSRS score was improved at 12 weeks (p = 0.039). Targeted metabolomics in plasma showed significant alterations in some metabolites associated with psychological symptoms, such as O-phosphoethanolamine. No significant differences were found between pre- and posttreatment levels of clinical bioactive substances related to stress and inflammation, oxidative levels, and the gut microbiota in this cohort. No serious adverse events occurred., Conclusion: Kamikihito ameliorated psychological and gastrointestinal symptoms in patients with chronic constipation. In parallel with the onset of efficacy, kamikihito modulated some anxiety-related metabolites. Kamikihito was safe and well-tolerated., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Human muscle fiber composition is heterogeneous and mainly determined by genetic factors. A previous study reported that experimentally induced iron deficiency in rats increases the proportion of fast-twitch muscle fibers. Iron status has been reported to be affected by genetic factors. As the TMPRSS6 rs855791 T/C and HFE rs1799945 C/G polymorphisms are strongly associated with iron status in humans, we hypothesized that the genotype score (GS) based on these polymorphisms could be associated with the muscle fiber composition in humans. Herein, we examined 214 Japanese individuals, comprising of 107 men and 107 women, for possible associations of the GS for iron status with the proportion of myosin heavy chain (MHC) isoforms (I, IIa, and IIx) as markers of muscle fiber composition. No statistically significant correlations were found between the GS for iron status and the proportion of MHC isoforms in all participants. When the participants were stratified based on sex, women showed positive and negative correlations of the GS with MHC-IIa (age-adjusted p = 0.020) and MHC-IIx (age-adjusted p = 0.011), respectively. In contrast, no correlation was found in men. In women, a 1-point increase in the GS was associated with 2.42% higher MHC-IIa level and 2.72% lower MHC-IIx level. Our results suggest that the GS based on the TMPRSS6 rs855791 T/C and HFE rs1799945 C/G polymorphisms for iron status is associated with muscle fiber composition in women.

INTELLANCE-J was a phase 1/2 study of a potent antibody-drug conjugate targeting epidermal growth factor receptor (EGFR), depatuxizumab mafodotin (Depatux-M), as a second- or first-line therapy, alone or combined with chemotherapy or chemoradiotherapy in 53 Japanese patients with World Health Organization (WHO) grade III/IV glioma. In second-line arms, patients with EGFR-amplified recurrent WHO grade III/IV glioma received Depatux-M plus chemotherapy (temozolomide) or Depatux-M alone regardless of EGFR status. In first-line arms, patients with newly diagnosed WHO grade III/IV glioma received Depatux-M plus chemoradiotherapy. The study was halted following lack of survival benefit with first-line Depatux-M in the global trial INTELLANCE-1. The primary endpoint was 6-month progression-free survival (PFS) in patients with EGFR-amplified tumors receiving second-line Depatux-M plus chemotherapy. Common nonocular treatment-emergent adverse events (TEAEs) with both second-line and first-line Depatux-M included lymphopenia (42%, 33%, respectively), thrombocytopenia (39%, 47%), alanine aminotransferase increase (29%, 47%), and aspartate aminotransferase increase (24%, 60%); incidence of grade ≥3 TEAEs was 66% and 53%, respectively. Ocular side effects (OSEs) occurred in 93% of patients receiving second-line Depatux-M plus chemotherapy and all patients receiving second-line Depatux-M alone or first-line Depatux-M plus chemoradiotherapy. Most OSEs were manageable with dose modifications and concomitant medications. The 6-month PFS estimate was 25.6% (95% confidence interval [CI] 11.4-42.6), and median PFS was 2.1 months (95% CI 1.9-3.9) with second-line Depatux-M plus chemotherapy in the EGFR-amplified subgroup. This study showed acceptable safety profile of Depatux-M alone or plus chemotherapy/chemoradiotherapy in Japanese patients with WHO grade III/IV glioma. The study was registered at ClinicalTrials.gov (NCT02590263)., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

We conducted a prospective multicenter trial to compare the usefulness of 11 C-methionine (MET) and 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for identifying tumor recurrence. Patients with clinically suspected tumor recurrence after radiotherapy underwent both 11 C-MET and 18 F-FDG PET. When a lesion showed a visually detected uptake of either tracer, it was surgically resected for histopathological analysis. Patients with a lesion negative to both tracers were revaluated by magnetic resonance imaging (MRI) at 3 months after the PET studies. The primary outcome measure was the sensitivity of each tracer in cases with histopathologically confirmed recurrence, as determined by the McNemar test. Sixty-one cases were enrolled, and 56 cases could be evaluated. The 38 cases where the lesions showed uptake of either 11 C-MET or 18 F-FDG underwent surgery; 32 of these cases were confirmed to be subject to recurrence. Eighteen cases where the lesions showed uptake of neither tracer received follow-up MRI; the lesion size increased in one of these cases. Among the cases with histologically confirmed recurrence, the sensitivities of 11 C-MET PET and 18 F-FDG PET were 0.97 (32/33, 95% confidence interval [CI]: 0.85-0.99) and 0.48 (16/33, 95% CI: 0.33-0.65), respectively, and the difference was statistically significant (P < .0001). The diagnostic accuracy of 11 C-MET PET was significantly better than that of 18 F-FDG PET (87.5% vs. 69.6%, P = .033). No examination-related adverse events were observed. The results of the study demonstrated that 11 C-MET PET was superior to 18 F-FDG PET for discriminating between tumor recurrence and radiation-induced necrosis., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: Resistance training has been recommended as an effective measure against age-related loss of muscle mass and muscle strength, called sarcopenia, even in older adults. However, despite subjecting each participant to the same training program, the training effect solely depended on the individual. This study aimed to evaluate whether certain blood parameters influenced the effect of a low-load resistance training program on muscle thickness in the community-dwelling elderly population., Methods: Sixty-nine community-dwelling Japanese (49 women and 20 men) subjects aged 69.4 ± 6.5 years were included. Low-load resistance training was performed twice a week for 12 weeks. Muscle thickness at the anterior aspects of the thigh (AT) was measured using a B-mode ultrasound device, and 22 blood parameter levels were assessed before and after the program. We checked the first quartile value of each parameter to establish cutoff values, and participants were divided into low or normal groups for each parameter., Results: A low-load resistance training program significantly increased muscle thickness at the AT. The interaction between time and groups was examined at low (< 4.1 g/dL) versus normal (≥ 4.1 g/dL) serum albumin (Alb) levels. Although there was no difference in muscle thickness at the AT before the training intervention, the hypertrophic effects were higher in the normal serum Alb level group than in the low serum Alb level group. The binomial logistic regression analysis showed that participants in the low serum Alb group had an odds ratio of 7.08 for decreased muscle thickness at the AT. The effect of a low-load resistance training program on lower limb muscle thickness appears to be limited in participants with low serum Alb levels before training interventions., Conclusions: Serum Alb level may act as a biomarker to predict the effects of low-load resistance training programs on muscle hypertrophy in elderly individuals., Trial Registration: This study was retrospectively registered in UMIN-Clinical Trial Registry (CTR), ID: UMIN000042759 (date of registration, 14 Dec 2020)., (© 2021. The Author(s).)

We conducted a field experiment in soybean with different levels of K application to elucidate the comparative dynamics of 137 Cs and K. The inventory of K in the shoots increased substantially from the fifth trifoliate stage to the full seed stage, and as the absorption of K increased, so too did the absorption of 137 Cs. Overall, the effect of K application was much greater in terms of 137 Cs dynamics than K dynamics or biomass production. K application reduced not only the accumulation of 137 Cs in the shoots, but also the distribution of 137 Cs to the grains. However, the decrease of 137 Cs distribution to the grain had a much smaller effect on 137 Cs accumulation in the grains than 137 Cs absorption. A positive correlation was also observed between the exchangeable 137 Cs/K ratio in the soil and the 137 Cs/K ratio in the shoots for each growth stage, and the 137 Cs/K ratios in the shoots at the full seed and full maturity stage were much higher than those at the fifth trifoliate and full bloom stage under the same exchangeable 137 Cs/K ratio in the soil. These findings suggest a decrease in the discrimination of 137 Cs from K during absorption after the full bloom stage. As a result of this and the increase in soil-exchangeable 137 Cs/K with growth, radiocesium was more transferable to the shoots after the full bloom stage. Overall, these results suggest that lowering the soil-exchangeable radiocesium/potassium ratio after the full bloom stage by increasing K availability could efficiently reduce the transfer of radiocesium to the grains., (Copyright © 2021 Elsevier Ltd. All rights reserved.)