Property of hepatitis B virus replication in Tupaia belangeri hepatocytes

AbstractThe northern treeshrew (Tupaia belangeri) has been reported to be an effective candidate for animal infection model with hepatitis B virus (HBV). The objective of our study was to analyze the growth characteristics of HBV in tupaia hepatocytes and the host response to HBV infection. We established primary tupaia hepatocytes (3–6-week old tupaia) and infected them with HBV genotypes A, B and C, and all the genotypes proliferated as well as those in human primary hepatocytes (>105 copies/ml in culture supernatant). We next generated a chimeric mouse with tupaia liver by transplantation of tupaia primary hepatocytes to urokinase-type plasminogen activator cDNA (cDNA-uPA)/severe combined immunodeficient (SCID) mice and the replacement ratio with tupaia hepatocytes was found to be more than 95%. Infection of chimeric mice with HBV (genotypes B, C, and D) resulted in HBV-DNA level of 104-106 copies/ml after 8 weeks of infection, which were almost similar to that in humanized chimeric mouse. In contrast, serum HBV level in adult tupaia (1-year-old tupaia) was quite low (<103 copies/ml). Understanding the differences in the response to HBV infection in primary tupaia hepatocytes, chimeric mouse, and adult tupaia will contribute to elucidating the mechanism of persistent HBV infection and viral eradication. Thus, T. belangeri was found to be efficient for studying the host response to HBV infection, thereby providing novel insight into the pathogenesis of HBV

Attitude of young psychiatrists toward coercive measures in psychiatry: a case vignette study in Japan

<p>Abstract</p> <p>Background</p> <p>Every psychiatrist must pay careful attention to avoid violating human rights when initiating coercive treatments such as seclusion and restraint. However, these interventions are indispensable in clinical psychiatry, and they are often used as strategies to treat agitated patients. In this study, we investigated young psychiatrists' attitudes toward psychiatric coercive measures.</p> <p>Methods</p> <p>A total of 183 young psychiatrists participated as subjects in our study. A questionnaire with a case vignette describing a patient with acute psychosis was sent to the study subjects via the Internet or by mail. This questionnaire included scoring the necessity for hospitalization, and the likelihood of prescribing seclusion and/or restraint, on a 9-point Likert scale (with 9 indicating strong agreement).</p> <p>Results</p> <p>There was general agreement among the study subjects that the case should be admitted to a hospital (8.91 ± 0.3) and secluded (8.43 ± 1.0). The estimated length of hospitalization was 13.53 ± 6.4 weeks. Regarding the likelihood of prescribing restraint, results showed great diversity (5.14 ± 2.5 on 9-point scale); psychiatrists working at general hospitals scored significantly higher (6.25 ± 2.5) than those working at university hospitals (5.02 ± 2.3) or psychiatric hospitals (4.15 ± 2.6). A two-group comparison of the length of inpatient care revealed a significant difference between those psychiatrists who scored 1-3 (n = 55, 14.22 ± 7.4 wks) and those who scored 7-9 (n = 62, 12.22 ± 4.0) regarding the need to use restraint.</p> <p>Conclusion</p> <p>Our results may reflect the current dilemma in Japanese psychiatry wherein psychiatrists must initiate coercive measures to shorten hospitalization stays. This study prompted its subject psychiatrists to consider coercive psychiatric treatments.</p

Suicidal ideation and burnout among psychiatric trainees in Japan

AIM: Burnout is a psychological condition that may occur in all workers after being exposed to excessive work-related stresses. We investigated suicidal ideation and burnout among Japanese psychiatric trainees as a part of the Burnout Syndrome Study (BoSS) International.  METHODS: In the Japanese branch, 91 trainees fully completed suicide ideation and behaviour questionnaire (SIBQ) and Maslach Burnout Inventory-General Survey (MBI-GS).  RESULTS: Passive suicidal ideation was reported by 38.5% of Japanese trainees and 22.0% of them had experienced active suicidal ideation. The burnout rate among Japanese subjects was 40.0%. These results were worse compared to the all 1980 trainees who fully completed the main outcome measure in BoSS International, 25.9%, 20.4% and 36.7%, respectively.  CONCLUSIONS: Our results suggest a higher risk of suicide among Japanese residents. Japan has a higher suicide rate than other countries. Early detection of, and appropriate intervention for, suicidal ideation is important in preventing suicide in psychiatry residents

Plasma Cathepsin S and Cathepsin S/Cystatin C Ratios Are Potential Biomarkers for COPD

Purpose. This study aimed to examine whether plasma levels of cathepsin S or its inhibitor, cystatin C, may serve as biomarkers for COPD. Patients and Methods. We measured anthropometrics and performed pulmonary function tests and chest CT scans on 94 patients with COPD and 31 subjects with productive cough but no airflow obstruction (“at risk”; AR). In these subjects and in 52 healthy nonsmokers (NS) and 66 healthy smokers (HS) we measured plasma concentrations of cathepsin S and cystatin C using an ELISA. Data were analyzed using simple and logistic regression and receiver operating characteristic analyses. Results. Cathepsin S and cystatin C plasma levels were significantly higher in the COPD and AR groups than in the NS and HS groups (p < 0.01). Among the COPD patients and AR subjects, plasma cathepsin S levels and cathepsin S/cystatin C ratios, but not cystatin C levels, were negatively related to severe airflow limitation (% FEV1 predicted < 50%; p = 0.005) and severe emphysema as assessed by low attenuation area (LAA) score on chest CT scans (LAA ≥ 8.0; p = 0.001). Conclusion. Plasma cathepsin S and cathepsin S/cystatin C ratios may serve as potential biomarkers for COPD

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Visualizing Web Images Using Fisher Discriminant Locality Preserving Canonical Correlation Analysis

A novel dimensionality reduction method, Fisher Discriminant Locality Preserving Canonical Correlation Analysis (FDLPCCA), for visualizing Web images is presented in this paper. FDLP-CCA can integrate two modalities and discriminate target items in terms of their semantics by considering unique characteristics of the two modalities. In this paper, we focus onWeb images with text uploaded on Social Networking Services for these two modalities. Specifically, text features have high discriminate power in terms of semantics. On the other hand, visual features of images give their perceptual relationships. In order to consider both of the above unique characteristics of these two modalities, FDLPCCA estimates the correlation between the text and visual features with consideration of the cluster structure based on the text features and the local structures based on the visual features. Thus, FDLP-CCA can integrate the different modalities and provide separated manifolds to organize enhanced compactness within each natural cluster

FTY720 Attenuates Neuropathic Pain after Spinal Cord Injury by Decreasing Systemic and Local Inflammation in a Rat Spinal Cord Compression Model

Neuropathic pain severely impairs rehabilitation and quality of life after spinal cord injury (SCI). The sphingosine-1-phosphate receptor agonist, FTY720, plays an important protective role in neuronal injury. This study aims to examine the effects of FTY720 in a rat acute SCI model, focusing on neuropathic pain. Female rats with SCI induced by 1-min clip compression were administered vehicle or 1.5mg/kg of FTY720 24 h after the injury. Using the mechanical nociceptive threshold test, we monitored neuropathic pain and performed histological analysis of the pain pathway, including the μ opioid receptor (MOR), hydroxytryptamine transporter (HTT), and calcitonin gene-related peptide (CGRP). Motor score, SCI lesion volume, residual motor axons, inflammatory response, glial scar, and microvascular endothelial dysfunction were also compared between the two groups. FTY720 treatment resulted in significant attenuation of post-traumatic neuropathic pain. It also decreased systemic and local inflammation, thereby reducing the damaged areas and astrogliosis and resulting in motor functional recovery. Whereas there was no difference in the CGRP expression between the two groups, FTY720 significantly preserved the MOR in both the caudal and rostral areas of the spinal dorsal horn. Whereas HTT was preserved in the FTY720 group, it was significantly increased in the rostral side and decreased in the caudal side of the injury in the vehicle group. These results suggest that FTY720 ameliorates post-traumatic allodynia through regulation of neuroinflammation, maintenance of the blood?brain barrier, and inhibition of glial scar formation, thereby preserving the connectivity of the descending inhibitory pathway and reducing neuropathic pain

Internet Addiction, Smartphone Addiction, and Hikikomori Trait in Japanese Young Adult: Social Isolation and Social Network

Background: As the number of internet users increases, problems related to internet overuse are becoming more and more serious. Adolescents and youth may be particularly attracted to and preoccupied with various online activities. In this study, we investigated the relationship of internet addiction, smartphone addiction, and the risk of hikikomori, severe social withdrawal, in Japanese young adult. Methods: The subjects were 478 college/university students in Japan. They were requested to complete the study questionnaire, which consisted of questions about demographics, internet use, the Internet Addiction Test (IAT), the Smartphone Addiction Scale (SAS)–Short Version (SV), the 25-item Hikikomori Questionnaire (HQ-25), etc. We investigated the difference and correlation of the results between two groups based on the purpose of internet use or the total score of each self-rating scale, such as screened positive or negative for the risk of internet addiction, smartphone addiction, or hikikomori. Results: There was a trend that males favored gaming in their internet use while females used the internet mainly for social networking via smartphone, and the mean SAS-SV score was higher in females. Two-group comparisons between gamers and social media users, according to the main purpose of internet use, showed that gamers used the internet longer and had significantly higher mean IAT and HQ-25 scores. Regarding hikikomori trait, the subjects at high risk for hikikomori on HQ-25 had longer internet usage time and higher scores on both IAT and SAS-SV. Correlation analyses revealed that HQ-25 and IAT scores had a relatively strong relationship, although HQ-25 and SAS-SV had a moderately weak one. Discussion: Internet technology has changed our daily lives dramatically and altered the way we communicate as well. As social media applications are becoming more popular, users are connected more tightly to the internet and their time spent with others in the real world continues to decrease. Males often isolate themselves from the social community in order to engage in online gaming while females use the internet as to not be excluded from their communications online. Mental health providers should be aware of the seriousness of internet addictions and hikikomori