CCL19-CCR7経路が肥満及びインスリン抵抗性に及ぼす影響に関する検討

広島大学(Hiroshima University)博士(歯学)Doctor of Philosophy in Dental Sciencedoctora

環境因子が健康に与える影響について インターネット調査;WDQH(Web-based Daily Questionnaire for Health)を利用した環境疫学調査

With increasing Internet coverage, the use of a web-based survey for epidemiological study is a possibility. We performed an investigation in Japan in winter 2008 using the web-based daily questionnaire for health (WDQH). The WDQH is a web-based questionnaire survey formulated to obtain information about the daily physical condition of the general public on a real-time basis, in order to study correlations between changes in physical health and changes in environmental factors. Respondents were asked whether they felt ill and had specific symptoms including fever. We analysed the environmental factors along with the health conditions obtained from the WDQH. Four factors were found to influence health: minimum temperature, hours of sunlight, median humidity and weekday or holiday. The WDQH allowed a daily health survey in the general population in real time via the Internet.博士（医学）・甲第593号・平成24年11月27日© 2013 Taylor & Francis Grou

箸動作利き手交換における効果的練習方法の検討 : 脳血流動態，難易度及びパフォーマンスの観点から

研究報告Original Articles　背景：作業療法では，脳血管疾患後，利き手が麻痺した際に箸動作利き手交換を行う．これまで経験的に，つまみやすい箸から日常の箸に，つまみ易い物から難しい物へと段階づけて練習を行ってきた．　目的：箸動作利き手交換の方法について，実験的検討を行い，効果的方法を提案する．方法：右利き健常男性11 名に，非利き手で3 種の箸（箸ぞう，割り箸，塗り箸），物体（スポンジ，木片，大豆）について計9 課題のデータ収集を行った．測定項目： 1．主観的難易度（難易度），2．つかみ離しが出来た個数（パフォーマンス）3．前頭前野領域脳血流動態とした．　結果：①脳血流量は難易度が高いと判断された課題は多く増加した．②注意・集中ができパフォーマンスにおいてミスが少ない場合に増加した．③課題の難易度は対象者の主観（課題の特性・傾向）より4 段階に分類された．その結果，箸動作の利き手交換練習の効果的方法の順番は，箸ぞう−木片 ，箸ぞう−スポンジ，割り箸−スポンジ，割り箸−木片， 塗り箸−スポンジ，箸ぞう−大豆 ，塗り箸−木片，割り箸−大豆，塗り箸−大豆が良いことが示唆された．　[Introduction] Chopsticks are traditionally used at meals in Japan. In case of dominant hand paralysis after stroke, exchange of dominant hand for chopstick manipulation is performed in occupational therapy. Practices are performed conventionally in a phased manner using easyto-manipulate chopsticks first and those of ordinary types later and easy-to-pickup objects first and hard-to-pickup ones later. [Objective] Propose effective methods for exchanging dominant hand of chopstick manipulation after experimental review. [Method] Collect data of nine types of tasks making 11 healthy right-handed males manipulate objects (2cm3 of sponge and wood chip soybeans) using three types of chopsticks (Hashizo, throwaway chopsticks, lacquered chopsticks) by non-dominant hand. Measurement items: ① Cerebral blood flow kinetics in prefrontal area, ② Difficulty level, ③ Number of objects picked up and released successfully (performance) Each task performed within 30 seconds [Results] Difficulty level was higher and performance was better in orders of Hashizo, throwaway chopsticks and lacquered chopsticks, and wood chip, sponge and soybeans respectively. With larger difference in cerebral blood flow between individuals, its rate tended to be higher in tasks with low difficulty level and high performance (Hashizo-wood chip) and with high difficulty level and low performance (lacquered chopstickssoybeans) and lower in a task with moderate difficulty level and performance (lacquered chopsticks-wood chip) as a result of consideration in order. [Discussion] Such tendency was observed that cerebral blood flow increased in tasks achieved steadily and earlier and those with significant difficulty and decreased in tasks required for concentration and carefulness. It was suggested effective to provide tasks by considering their characteristics

理科教員の専門性を修得させるための一方策とその検証 ～理科指導法ＫＳＰ演習を通して～

理科教員には、学習内容を的確に理解させる指導力とともに科学に対する高度な認識をもつ専門的資質が求められている。その修得を目指す「理科指導法」授業においては、指導力に関する育成目標とともに、専門的資質についても、何をどの程度まで修得させるべきか明確にした授業計画が重要と考える。理学を専門とする本学で学んだ学生には、高い専門的資質を身に付けて教職に就いてもらいたい。この思いから、理科教員に求められる専門的資質の内容を整理し、それらを授業と関連させることで、科学理論や学問的背景を関連させた指導を実践できる教員を目指して演習を展開させている。ここで、その内容と成果や課題を報告する

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

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo