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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]

Purpose: To determine eye drop type and usage frequency and investigate risk factors for no eye drop use in individuals with symptomatic dry eye (DE) in Japan. Study design: Crowdsourced observational study. Methods: This study was conducted using the DryEyeRhythm smartphone application between November 2016 and September 2019. Data collected included the type and frequency of eye drop use, demographics, medical history, lifestyle, and self-reported symptoms. Symptomatic DE was defined as an Ocular Surface Disease Index total score of ≥ 13. Risk factors for no eye drop use were identified using multivariate logistic regression analyses. Results: Among 2619 individuals with symptomatic DE, 1876 did not use eye drops. The most common eye drop type was artificial tears (53.4%), followed by hyaluronic acid 0.1% (33.1%) and diquafosol sodium 3% (18.7%). Risk factors (odds ratio [95% confidence interval]) for no eye drop use were age (0.97 [0.97–0.98]), body mass index (1.04 [1.01–1.07]), brain disease (0.38 [0.15–0.98]), collagen disease (0.30 [0.13–0.68]), mental illness other than depression and schizophrenia (0.65 [0.45–0.93]), cataract surgery (0.12 [0.02–0.59]), ophthalmic surgery other than cataract and laser-assisted in situ keratomileusis (0.55 [0.34–0.88]), current (0.47 [0.38–0.57]) or past (0.58 [0.43–0.77]) contact lens use, >8 h screen exposure time (1.38 [1.05–1.81]), <6 h (1.24 [1.01–1.52]) and >9 h (1.34 [1.04–1.72]) sleep time, and water intake (0.97 [0.94–0.98]). Conclusion: Many participants with symptomatic DE did not use optimized eye drop treatment and identified risk factors for no eye drop use. The DryEyeRhythm application may help improve DE treatment. [ABSTRACT FROM AUTHOR]

Background: Obesity is a public health problem worldwide. To widely disseminate weight-loss interventions across the target population, a cost-effective approach is needed. Objective: We aimed to test whether a single motivational lecture could promote weight loss. Methods: Our study was a 3-month randomized controlled trial, and we recruited participants via local newspaper advertisements in 3 cities in Ibaraki Prefecture, Japan, and randomly assigned them to a control group (no intervention) and an intervention group, who attended a single motivational lecture lasting approximately 2 h. No other lectures or textbooks were provided. The eligibility criteria included an age of 40–64 years, a body mass index (BMI) of 25–40 kg/m2, and the presence of at least 1 component of metabolic syndrome. The primary outcome was body weight change at 3 months. Results: We enrolled 145 eligible participants with a mean age of 53.8 ± 7.1 years and a BMI of 28.5 ± 3.1 kg/m2. The 3-month body weight change in the control and intervention groups was –0.65 kg (95% confidence interval [CI] –1.09 to –0.20) and –2.48 kg (95% CI –3.01 to –1.95), respectively. The between-group difference was 1.83 kg (95% CI 1.15–2.51). Conclusions: The significant difference suggested that a single motivational lecture is an effective option to promote modest weight loss in the short term. [ABSTRACT FROM AUTHOR]

Abstract: Background: Despite the presence of ganglion cells in the rectum, some patients have symptoms similar to those of Hirschsprung's disease. A consensus has yet to be established regarding the terminology for these diseases. We defined this group of diseases as “allied disorders of Hirschsprung's disease” and compiled these guidelines to facilitate accurate clinician diagnosis and provide appropriate treatment strategies for each disease. Methods: These guidelines were developed using the methodologies in the Medical Information Network Distribution System (MINDS). Of seven allied disorders, isolated hypoganglionosis; megacystis‐microcolon‐intestinal hypoperistalsis syndrome; and chronic idiopathic intestinal pseudo‐obstruction were selected as targets of clinical questions (CQ). In a comprehensive search of the Japanese‐ and English‐language articles in PubMed and Ichu‐Shi Web, 836 pieces of evidence related to the CQ were extracted from 288 articles; these pieces of evidence were summarized in an evidence table. Results: We herein outline the newly established Japanese clinical practice guidelines for allied disorders of Hirschsprung's disease. Given that the target diseases are rare and intractable, most evidence was drawn from case reports and case series. In the CQ, the diagnosis, medication, nutritional support, surgical therapy, and prognosis for each disease are given. We emphasize the importance of full‐thickness intestinal biopsy specimens for the histopathological evaluation of enteric ganglia. Considering the practicality of the guidelines, the recommendations for each CQ were created with protracted discussions among specialists. Conclusions: Clinical practice recommendations for allied disorders of Hirschprung's disease are given for each CQ, along with an assessment of the current evidence. We hope that the information will be helpful in daily practice and future studies. [ABSTRACT FROM AUTHOR]

Background: Patients with hypoalbuminemia often fail to respond to increased doses of loop diuretics. We therefore performed a post hoc analysis to investigate the pharmacological action of tolvaptan and whether it is dependent on the serum albumin level.Methods: This analysis was based on four previous clinical trials of tolvaptan in patients with liver cirrhosis who exhibited insufficient response to conventional diuretics. We analyzed the correlation between the change in the initial 24-h cumulative urine volume from baseline and the serum albumin level at baseline, and assessed potential predictive factors of response to tolvaptan.Results: The correlation coefficient was 0.029 in the placebo group and -0.112 in the 7.5 mg tolvaptan group of patients with liver cirrhosis. Administration of tolvaptan provoked a stable response regardless of the serum albumin level. Tolvaptan use was identified as a significant predictor of pharmacological action, and was shown to change the initial urine volume by 885 mL (P < 0.0001) in liver cirrhosis patients.Conclusions: In this post hoc analysis, tolvaptan increased the initial urine volume from baseline regardless of serum albumin levels. Use of tolvaptan as an add-on therapy to loop diuretics can be considered an optimal therapeutic option in patients with insufficient response to loop diuretics. [ABSTRACT FROM AUTHOR]

To study the male and female lineages of East Asian and European humans, we have sequenced 25 short tandem repeat markers on 453 Y-chromosomes and collected sequences of 72 complete mitochondrial genomes to construct independent phylogenetic trees for male and female lineages. The results indicate that East Asian individuals fall into two clades, one that includes East Asian individuals only and a second that contains East Asian and European individuals. Surprisingly, the European individuals did not form an independent clade, but branched within in the East Asians. We then estimated the divergence time of the root of the European clade as ∼41,000 years ago. These data indicate that, contrary to traditional views, Europeans diverged from East Asians around that time. We also address the origin of the Ainu lineage in northern Japan. [ABSTRACT FROM AUTHOR]

Yokukansan (YKS) has been used in Japan as a remedy for neurosis, insomnia, and children with night crying. In a previous study, we reported that YKS controls scratching behavior and inhibits the development of atopic dermatitis (AD)-like lesions in NC/Nga mice. In this study, we investigated the effects of YKS on the development of AD-like lesions in socially isolated NC/Nga mice compared with the effects of fexofenadine and elucidated the mechanism of the ameliorating effect of YKS on the skin lesions. Ten-week-old male NC/Nga mice were divided into three groups ( n = 5/group): the conventional control, the YKS-treated, and the fexofenadine-treated groups, and were kept isolated under conventional conditions for 6 weeks. Measurements were made of dermatitis scores and transepidermal water loss (TEWL), scratching and grooming behaviors. Immunohistochemistry and mRNA levels were also evaluated. We performed similar experiments under specific pathogen free (SPF) conditions that served as a SPF control. YKS and fexofenadine inhibited the aggravation of skin lesions and decreased TEWL, but only YKS decreased the numbers of scratching and pathologic grooming behaviors. Immunohistochemistry and RT-PCR revealed that N-methyl- d-aspartate (NMDA) receptor expression was increased in the skin of conventional control mice and was decreased in YKS-treated mice. Glutamate transporter-1 (GLT-1) mRNA levels were decreased in the skin of conventional control mice and were increased in YKS-treated mice. The results indicate that YKS ameliorates AD-like skin lesions in NC/Nga mice through a mechanism distinct from that of fexofenadine. Furthermore, the effects of YKS are suggested to be mediated via glutamate signaling in the skin lesions. [ABSTRACT FROM AUTHOR]

Aim: To describe clinical practice and research activities for early psychiatric intervention in Japan, a country with a huge number of psychiatric beds and a history of long-stay, hospital-based psychiatry. Methods: The characteristics, methods and activities of early intervention studies and implementation at four leading institutions in Japan are described. Results: The Tokyo Youth Club (Tokyo), the Department of Neuropsychiatry of Toyama University Hospital (Toyama), the endai t-risk Mental State and irst pisode (SAFE) service (Sendai), and the Il Bosco of Toho University Omori Medical Center (Tokyo) have unique and active psychiatric programmes. Eachcentre has its own clinical research programme and treatment strategies. The Japanese Society for the Prevention of Psychiatric Disorders, founded in 1996, has made a steady contribution to psychiatric care by providing a forum for members to promote best practices for early intervention and by hosting annual meetings to discuss research and treatment. Conclusions: The Japanese psychiatry service is continuing its transition from hospital-based psychiatry to community-based psychiatry. Despite these difficult circumstances, the publication of data on the duration of untreated psychosis in Japan along with evidence that early detection determines outcome has encouraged new attempts to promote early psychiatric intervention. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to identify the relationship between duration of untreated psychosis (DUP), premorbid functioning, and cognitive dysfunction and the outcome of first-episode schizophrenia. Method: Thirty-four neuroleptic-naive patients who consulted hospitals in Tokyo and who were treated by psychiatrists for the first time were evaluated with regard to DUP, premorbid functioning, psychiatric symptoms, and global functioning. The neuropsychological test battery consisted of the Letter Cancellation Test, Trail-Making Test, Digit Span and Verbal Fluency Test. One year later, 24 of the subjects were reassessed for psychiatric symptoms, global functioning, and social functioning, and the relationships between DUP, premorbid functioning, and cognitive performance and the outcome was investigated. Results: Short DUP, good premorbid functioning, and good Letter Cancellation Test, Digit Span and Verbal Fluency Test scores were significantly associated with good outcome. Conclusions: The present results in a Japanese sample are consistent with previous international evidence that delay of initial treatment, premorbid functioning, and cognitive deficits are associated with outcome. A major limitation of the present study was the small size of the subject group. But because the subjects were relatively homogeneous and not influenced by psychoactive substances, the results reflect the essence of the disorder. [ABSTRACT FROM AUTHOR]

The objective of the present study was to clarify the characteristics of weed vegetation in no-tillage upland fields in Japan. Vegetation surveys were conducted in two stages and the obtained data were analyzed based on the multiplied dominance ratio. The first was a two-year survey of a no-tillage field and a tilled field where no-tillage or tillage farming had been carried out for more than 10 years. The no-tillage field surveyed exhibited a different seasonal succession from the tilled field. Summer annuals dominated the tilled field in summer, and winter annuals dominated in spring. Perennials occupied the no-tillage field in spring; summer annuals also dominated in summer. The second survey was of 19 and 22 fields, including some no-tillage fields, in the summer of 2000 and the spring of 2001. The vegetation in both summer and spring was classified into three vegetation types, principally dependent on the no-tillage periods: types I and II consisted mainly of tilled and under 3-year-old no-tillage fields, and type III comprised no-tillage fields three years old or over. Type II vegetation was characterized primarily by the presence of biennials and perennials of Asteraceae, and type III by perennials, such as sweet vernalgrass (Anthoxanthum odoratum ), in addition to the same species as type II. Summer annuals such as southern crabgrass (Digitaria ciliaris ) were abundant in many fields in summer regardless of the vegetation types. [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]

We assessed the sensitivities of several methods for detecting Helicobacter pylori (culture, histology, rapid urease test, and serology), and evaluated the H. pylori positivity considering the degree of atrophy in the background mucosa in 202 gastric cancer patients and 101 controls. The positivity of H. pylori determined by culture (81%) was significantly higher than that determined by serology (62%) in gastric cancer patients (P < 0.001). The positivities of H. pylori determined by biopsy and/or serology in intestinal (84%) and diffuse (95%) types of gastric cancer were higher than that observed in controls (54%) (P < 0.001). Intestinal-type gastric cancer tended to occur in the atrophic mucosa, in which H. pylori positivity was not different from that in controls after adjusting for the degree of atrophy, whereas diffuse-type gastric cancer was observed more often in the nonatrophic mucosa, in which H. pylori positivity was higher than that in controls even after adjusting for the degree of atrophy. [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.)

Background: Portopulmonary hypertension (PoPH) is a subtype of the pulmonary arterial hypertension (PAH) associated with portal hypertension. There is a dissociation between the proportion of PoPH in PAH and that of PoPH in patients with liver cirrhosis, suggesting PoPH underdiagnosis and an incomplete understanding of this entity in the clinical setting. Specifically, real-world data in Japan is largely unknown as compared with in Europe and the United States. The present study aims to elucidate the prevalence and etiology of PoPH in Japanese patients with chronic liver disease., Methods and Design: In this prospective, single-center, observational investigation of PoPH patients with chronic liver disease, a targeted 2,500 Japanese adult patients regularly visiting Shinshu University Hospital in Matsumoto, Japan, for chronic liver disease will complete a standardized questionnaire on the presence of PoPH symptoms. If the respondent has signs of possible PoPH, ultrasound echocardiography (UCG) will be performed as a primary screening. In the case that UCG findings indicate pulmonary hypertension, the patient will be referred to a cardiologist for further evaluation, whereby a definitive diagnosis PoPH can be made. PoPH prevalence and etiology will be investigated at the time of diagnosis. Afterwards, patients with PoPH will be followed for five years for determination of survival rate., Discussion: This study will reveal the prevalence, etiology, and 5-year survival rate of PoPH in Japanese patients with chronic liver disease., Trial Registration: This study is being performed at Shinshu University following registration as UMIN 000042287 on October 29, 2020., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To replicate previous genome-wide association study identified sprint-related polymorphisms in 3 different cohorts of top-level sprinters and to further validate the obtained results in functional studies., Methods: A total of 240 Japanese, 290 Russians, and 593 Brazilians were evaluated in a case-control approach. Of these, 267 were top-level sprint/power athletes. In addition, the relationship between selected polymorphisms and muscle fiber composition was evaluated in 203 Japanese and 287 Finnish individuals., Results: The G allele of the rs3213537 polymorphism was overrepresented in Japanese (odds ratio [OR]: 2.07, P = .024) and Russian (OR: 1.93, P = .027) sprinters compared with endurance athletes and was associated with an increased proportion of fast-twitch muscle fibers in Japanese (P = .02) and Finnish (P = .041) individuals. A meta-analysis of the data from 4 athlete cohorts confirmed that the presence of the G/G genotype rather than the G/A+A/A genotypes increased the OR of being a sprinter compared with controls (OR: 1.49, P = .01), endurance athletes (OR: 1.79, P = .001), or controls + endurance athletes (OR: 1.58, P = .002). Furthermore, male sprinters with the G/G genotype were found to have significantly faster personal times in the 100-m dash than those with G/A+A/A genotypes (10.50 [0.26] vs 10.76 [0.31], P = .014)., Conclusion: The rs3213537 polymorphism found in the CPNE5 gene was identified as a highly replicable variant associated with sprinting ability and the increased proportion of fast-twitch muscle fibers, in which the homozygous genotype for the major allele (ie, the G/G genotype) is preferable for performance.

PPARGC1A rs8192678 G/A (Gly482Ser) and NRF1 rs6949152 A/G polymorphisms have been associated with endurance athlete status, endurance performance phenotypes, and certain health-related markers of different pathologies such as metabolic syndrome, diabetes, and dyslipidemia. We hypothesized that they could be considered interesting candidates for explaining inter-individual variations in muscle fiber composition in humans. We aimed to examine possible associations of these polymorphisms with myosin heavy-chain (MHC) isoforms as markers of muscle fiber compositions in vastus lateralis muscle in a population of 214 healthy Japanese subjects, aged between 19 and 79 years. No significant associations were found in men for any measured variables. In contrast, in women, the PPARGC1A rs8192678 A/A genotype was significantly associated with a higher proportion of MHC-I ( p = 0.042) and with a lower proportion of MHC-IIx ( p = 0.033), and the NRF1 rs6949152 AA genotype was significantly associated with a higher proportion of MHC-I ( p = 0.008) and with a lower proportion of MHC IIx ( p = 0.035). In women, the genotype scores of the modes presenting the most significant results for PPARGC1A rs8192678 G/A (Gly482Ser) and NRF1 rs6949152 A/G polymorphisms were significantly associated with MHC-I ( p = 0.0007) and MHC IIx ( p = 0.0016). That is, women with combined PPARGC1A A/A and NRF1 A/A genotypes presented the highest proportion of MHC-I and the lowest proportion of MHC-IIx, in contrast to women with combined PPARGC1A GG+GA and NRF1 AG+GG genotypes, who presented the lowest proportion of MHC-I and the highest proportion of MHC-IIx. Our results suggest possible associations between these polymorphisms (both individually and in combination) and the inter-individual variability observed in muscle fiber composition in women, but not in men.

Chronic subdural hematoma (CSDH) has a reported postoperative recurrence rate of 3-20% and the optimal therapeutic strategy remains controversial. Recently, in Japan, Goreisan (Kampo medicine) was used for preventing postoperative CSDH recurrence. Therefore, this study aimed to explore if Goreisan is effective against specific CSDH types by evaluating its effects on postoperative CSDH recurrence and reoperation rates based on its natural history and internal structure on CT images. This retrospective, single-center, cohort study was conducted at the Tokyo Metropolitan Hiroo Hospital. After applying the inclusion/exclusion criteria, data from 107 patients (70 men and 37 women; mean age, 77.1 ± 10.9 years), admitted for CSDH from January 2013 to December 2018, were included in the Goreisan group, whereas those of 122 patients (84 men and 38 women; mean age, 73.9 ± 13.3 years), admitted for CSDH from January 2007 to December 2012, were included in the control group. This corresponded to 114 lesions, with 14 reoperation lesions, in the Goreisan group and 108 lesions, with 16 reoperation lesions, in the control group. Lesions were categorized as homogeneous, laminar, separated, or trabecular type, and patients with homogeneous type lesions in the Goreisan group were approximately 50% less likely to undergo reoperation compared with those in the control group (7.3% versus 14%; odds ratio = 0.51; 95% confidence interval = 0.12-2.11). Thus, the homogeneous type CSDH was the most responsive to Goreisan, whereas the separated type was the least responsive. Therefore, selecting treatment strategies for preventing CSDH recurrence on CSDH type may contribute toward reducing reoperation rates., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Decreasing the transfer of radioactive cesium (RCs) from soil to crops has been important since the deposition of RCs in agricultural soil owing to the Fukushima nuclear power plant accident of 2011. We investigated the genotypic variation in RCs accumulation in 234 and 198 hexaploid wheat (Triticum spp.) varieties in an affected field in 2012 and 2013, respectively. The effects of soil exchangeable potassium (ExK) content to RCs accumulation in wheat varieties were also evaluated. A test field showed fourfold differences in soil ExK contents based on location, and the wheat varieties grown in areas with lower soil ExK contents tended to have higher grain RCs concentrations. RCs concentrations of shoots, when corrected by the soil ExK content, were positively significantly correlated between years, and RCs concentrations of shoots were significantly correlated with the grain RCs concentration corrected by the soil ExK content. These results indicated that there were genotypic variations in RCs accumulation. The grain to shoot ratio of RCs also showed significant genotypic variation. Wheat varieties with low RCs accumulations were identified. They could contribute to the research and breeding of low RCs accumulating wheat and to agricultural production in the area affected by RCs deposition.

Objectives: The Ocular Surface Disease Index (OSDI) questionnaire is widely used to evaluate subjective symptoms of dry eye disease (DED) as a primary diagnostic criterion. This study aimed to develop a Japanese version of the OSDI (J-OSDI) and assess its reliability and validity., Design and Setting: Hospital-based cross-sectional observational study., Participants: A total of 209 patients recruited from the Department of Ophthalmology at Juntendo University Hospital., Methods: We translated and culturally adapted the OSDI into Japanese. The J-OSDI was then assessed for internal consistency, reliability and validity. We also evaluated the optimal cut-off value to suspect DED using an area under the receiver operating characteristic curve (AUC) analysis., Primary Outcome Measures: Internal consistency, test-retest reliability and discriminant validity of the J-OSDI as well as the optimal cut-off value to suspect DED., Results: Of the participants, 152 had DED and 57 did not. The J-OSDI total score showed good internal consistency (Cronbach's alpha=0.884), test-retest reliability (interclass correlation coefficient=0.910) and discriminant validity by known-group comparisons (non-DED, 19.4±16.0; DED, 37.7±22.2; p<0.001). Factor validity was used to confirm three subscales within the J-OSDI according to the original version of the questionnaire. Concurrent validity was assessed by Pearson correlation analysis, and the J-OSDI total score showed a strong positive correlation with the Dry Eye-Related Quality-of-Life Score (γ=0.829). The optimal cut-off value of the J-OSDI total score was 36.3 (AUC=0.744)., Conclusions: The J-OSDI was developed and validated in terms of reliability and validity as an effective tool for DED assessment and monitoring in the Japanese population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To identify the key diagnostic features and causes of fever of unknown origin (FUO) in Japanese patients., Design: Multicentre prospective study., Setting: Sixteen hospitals affiliated with the Japanese Society of Hospital General Medicine, covering the East and West regions of Japan., Participants: Patient aged ≥20 years diagnosed with classic FUO (axillary temperature≥38.0°C at least twice within a 3-week period, cause unknown after three outpatient visits or 3 days of hospitalisation). A total of 141 cases met the criteria and were recruited from January 2016 to December 2017., Intervention: Japanese standard diagnostic examinations., Outcome Measures: Data collected include usual biochemical blood tests, inflammatory markers (erythrocyte sedimentation rate (ESR), C reactive (CRP) protein level, procalcitonin level), imaging results, autopsy findings (if performed) and final diagnosis., Results: The most frequent age group was 65-79 years old (mean: 58.6±9.1 years). The most frequent cause of FUO was non-infectious inflammatory disease. After a 6-month follow-up period, 21.3% of cases remained undiagnosed. The types of diseases causing FUO were significantly correlated with age and prognosis. Between patients with and without a final diagnosis, there was no difference in CRP level between patients with and without a final diagnosis (p=0.121). A significant difference in diagnosis of a causative disease was found between patients who did or did not receive an ESR test (p=0.041). Of the 35 patients with an abnormal ESR value, 28 (80%) had causative disease identified., Conclusions: Age may be a key factor in the differential diagnosis of FUO; the ESR test may be of value in the FUO evaluation process. These results may provide clinicians with insight into the management of FUO to allow adequate treatment according to the cause of the disease., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Nonvitamin K antagonist oral anticoagulants (NOACs) are considered superior, or at least noninferior, to warfarin in preventing stroke or systemic embolism in patients with nonvalvular atrial fibrillation. Here, we recruited acute ischemic stroke patients with nonvalvular atrial fibrillation and at least one cerebral microbleed (CMB), and evaluated the proportion of patients who had an increased number of CMBs (%) after receiving anticoagulant therapy with NOACs or with warfarin for 12 months., Methods: This was a multicenter, prospective, observational cohort study at 20 centers, conducted between 2015 and 2017, in which we recruited 85 patients with at least one CMB detected by 1.5T magnetic resonance imaging (T2*WI) at baseline, who received NOACs or warfarin for at least 12 months. We compared the proportions of patients with increased numbers of CMBs in the NOACs and warfarin treatment groups., Results: The proportions of patients with increased numbers of CMBs at month 12 of treatment were 28.6% and 66.7% in the NOACs and warfarin groups, respectively. The new CMBs showed no specific regional localization in either group. In the NOACs and warfarin groups, physicians prescribed lower-than-standard dosing in 13.3% and 50% of the cases, respectively. The administration of reduced doses at physicians' discretion did not appear to alter the incidence of new CMBs., Discussion: This is the first evidence to suggest efficacy of NOACs for preventing further CMBs in patients with at least one CMB, although no statistical evaluation was carried out., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The study aims to clarify the mechanism in patients with neurally mediated syncope (NMS), focusing on the adenylate cyclase (AC) activity level in lymphocytes. This study included 40 subjects: 22 healthy volunteers and 18 NMS patients. We investigated the changes in AC activity that occur during of syncope at rest and during the head-up tilt (HUT) test. We obtained 8 mL of blood at rest time and four times during the HUT test. Then, we measured the AC activity and the test reagent was added to the lymphocytes (10,000) and reacted for 30 min at room temperature. We were able to determine the standard value of AC activity when adrenaline (AD) and isoproterenol (IP) were added to lymphocytes. The results of our study showed one of the causes of NMS has a difference in AC activity level and classification of the patients into two different types of NMS was possible: either the vasodepressor type (VT) or mixed type (MT). At rest time, VT patients showed significantly higher AC activity (AD; 100 μM: p = 0.005, IP; 50 μM: p = 0.02) and MT patients showed significantly lower AC activity (AD; 10 μM: p = 0.02, IP; 50 μM: p = 0.004) than the average AC activity in healthy volunteers. Moreover, VT patients had significantly higher AC activity than healthy volunteers at the four points of the HUT test. MT patients had significantly lower AC activity (AD: p = 0.04 and IP: p = 0.04) than healthy volunteers at the rest time of HUT. Our study showed a significant difference in AC activities between NMS patients and healthy volunteers at rest. Therefore, a detailed NMS diagnosis can be made by examining AC activity levels in blood taken at rest time., Competing Interests: The authors have declared that no competing interests exist.

Background/aims: For hepatocellular carcinoma (HCC) within a single subsegment, the superiority of anatomical subsegmentectomy over non-anatomical partial resection is still controversial. In this study, we assessed the potential benefit of subsegmentectomy., Methodology: We selected 44 patients with a single HCC lesion within one subsegment who had undergone anatomical subsegmentectomy or non-anatomical partial resection from among 173 patients who underwent hepatectomy in our hospital from August 2003 to May 2013. We compared the results following anatomical subsegmentectomy (Group A; n = 16) and non-anatomical partial resection (Group N; n = 28)., Results: One- and two-year survival rates were 92.5% and 89.3%, respectively; 1- and 2-year recurrence-free survival (RFS) rates were 88.9% and 69.1%, respectively. There was no significant difference in overall survival or RFS between the groups. However, among HBV-positive patients, RFS was significantly better for Group A than Group N (p = 0.008)., Conclusions: For HBV-positive HCC within a single subsegment, we recommend subsegmentectomy.