握力は、糖尿病患者の心血管イベントの独立した予測因子である

Diabetes mellitus (DM) is associated with an increased incidence of cardiovascular events and an elevated prevalence of sarcopenia. However, the relationship between cardiovascular events and sarcopenia in patients with DM remains unclear. This study examined this relationship and investigated the predictors of cardiovascular events in this population.This study enrolled 161 patients with DM and no history of cardiovascular diseases who were admitted to our hospital for the treatment of DM between September 2012 and December 2015. Patients were divided into sarcopenia and non-sarcopenia groups, and were followed until March 2019. The primary endpoint was major adverse cardiovascular events (MACE).The mean age was 65.9 ± 1.8 years old and the mean follow-up period was 4.1 ± 0.8 years. The log-rank test indicated that MACE differed significantly between the two groups (P < 0.0001). Multivariate Cox hazard analysis identified the cardio-ankle vascular index (CAVI) and handgrip strength as independent predictors of MACE (hazard ratio [HR] = 1.18, P = 0.039; and HR = 0.70, P = 0.016, respectively).Handgrip strength is an indicator of sarcopenia in diabetic patients, and together with CAVI it was independently associated with the incidence of MACE. This suggests that the handgrip strength test might be useful in the management of patients with DM at high risk of cardiovascular outcomes.博士（医学）・乙第1493号・令和3年3月15日© 2021 by the International Heart Journal Association発行元であるインターナショナル・ハート・ジャーナル刊行会の許諾を得て登録（2021年6月23日付）ジャーナル公式サイト（J-STAGE内）：https://doi.org/10.1536/ihj.20-67

Effects of Sultopride and Sulpiride on Serum Prolactin Level in Schizophrenia.

Sultopride or sulpiride was administered to 26 schizophrenic patients. In the male patients, there was a significant correlation between serum concentrations of sultopride and sulpiride and prolactin response. In the female patients, there was no significant correlation between them. In sultopride treatment, prolaction response was suggested to be predictive of a good therapeutic response

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