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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]

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]

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]

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]

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]

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]

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]

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]