A Case of Dermatomyositis with Severe Myalgia and Muscle Weakness Testing Positive for Anti-melanoma Differentiation-associated Gene 5 Antibody

We report a case of a woman with typical dermatomyositis (DM) with skin manifestations, severe myalgia and muscle weakness complicated by interstitial lung disease (ILD) and pneumomediastinum. Pneumomediastinum persisted despite treatment with immunosuppressive therapy (steroids and cyclosporine). After the test for anti-melanoma differentiation-associated gene 5 (MDA5) antibody came out positive, we doubled the cyclosporine dose and her condition improved. Despite typical clinical features of DM, in cases complicated by pneumomediastinum or steroid resistance, measurement of anti-MDA5 antibody may be useful for immunosuppressant dose titration

The Actual Conditions of creation and utilization of the Records of Children with Disabilities during the School Transition Period: A Survey of Early Childhood Facilities and Elementary Schools

The purpose of this study is to clarify the actual conditions of personal records such as “support files” and “transition support sheets” created by early childhood facilities (kindergartens and nursery schools) to provide transition support to children with disabilities. The study seeks to examine how these records are created by early childhood facilities and used by elementary schools. A nationwide questionnaire survey targeting public and private kindergartens, nursery schools, and elementary schools was carried out. The survey results show that about half of the early childhood facilities created these records and that the records were being effectively utilized by the elementary schools that received them. However, there were also differences based on the type of institution: for instance, the rate of record creation was high at public kindergartens and low at private kindergartens and nursery schools. In terms of record content, there is a possibility of a gap between the information recorded by early childhood facilities and that sought by elementary schools. Based on these actual conditions, this study identifies issues to be considered in the effective creation and utilization of records.本研究は平成28年度文科省委託「幼児期の教育内容等深化・充実調査研究」（調査研究課題：幼保小接続における学習機会の保障としての合理的配慮に関する研究，研究受託機関：名古屋市立大学）の助成を受けて行われた研究成果の一部である。なお，本稿の一部は日本教育心理学会第59回総会において発表した

A Survey on Cooperation between Early Childhood Facilities and Elementary Schools regarding Children with Disabilities

This survey aimed to reveal the current conditions of cooperation between early childhood facilities and elementary schools regarding children with disabilities. A nationwide questionnaire was administered to 172 nursery schools (public), 242 nursery schools (private), 200 kindergartens (public), 481 kindergartens (private), and 592 elementary schools. Overall, for cooperation with elementary school for children with disabilities, the percentage of practice with kindergarten (public) was highest among early childhood facilities. In particular, for “Exchange activities between early childhood facilities and elementary schools” and “Introduction of approach curriculum,” the percentage of practice with kindergarten (public) was higher when compared with that in other early childhood facilities. The newly found information in this survey was that nursery schools (public) were most likely to take advantage of the “Individual education program.” The major problem was that nursery school and kindergarten teachers were willing to cooperate on early childhood education and care with elementary school teachers, but elementary school teachers answered that it was difficult to cooperate with many of the early childhood facilities. The ideal method for cooperation between early childhood facilities and elementary schools needs to be considered within each community.本研究は平成26年度文部科学省委託「幼児教育の改善・充実調査研究」（研究代表者：山崎 晃）及び平成25～27年度科学研究費・基盤研究（C）（研究課題番号：25381325，研究代表者：山崎 晃）の助成を受けて行われた研究成果の一部である

Long-term survival with RAS-associated autoimmune leukoproliferative disorder with somatic KRAS mutation:A case report

　RAS -associated autoimmune leukoproliferative disorder (RALD) is a recently reported rare nonmalignant autoimmune disorder. The characteristic clinical findings of RALD include monocytosis, leukocytosis, lymphoproliferation, and autoimmune phenomena. RALD is defined by somatic mutations in KRAS or NRAS . It is a new disease that was reported by Niemela and Takagi in 2011. The prognosis and incidence are currently unknown and the treatment strategy has not yet been established.　Here we describe the long-term survival of a patient with who displayed a somatic KRAS G12D mutation. His clinical features and labolatory data were overlapped with juvenile myelomonocytic leukemia and chronic myelomonocytic leukemia. Mercaptopurine hydrate, hydroxycarbamide and azacitizine were administered to control white blood cell count and improve clinical symptoms. He had a long survival time without hematopoietic stem cell transplantation

Mycobacterium tuberculosis releases an antacid that remodels phagosomes

International audienc

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