ドラッグデリバリーシステムによるアピゲニンの抗炎症効果の向上

筑波大学 (University of Tsukuba)201

ドラッグデリバリーシステムによるアピゲニンの抗炎症効果の向上

筑波大学 (University of Tsukuba)201

The Qualitative Analysis of Effective Work of Mourning by Victims' Family

平成13年6月8日に附属池田小学校で発生した児童殺傷事件の被害者遺族の一人である本郷由美子さんの手記『虹とひまわりの娘』を分析素材として、どんな悲嘆の対処法や社会的サポートがモーニングワークの促進に有効であるのかを探索的に探ることを研究の目的とした。加えて、「死者を殺す」というラガーシュ仮説の妥当性に関する若干の検討を行った。その結果、モーニングワークを通して親子の「絆」の結び直しがはかられ、娘に対する「愛の物語」が生成されていった過程が明らかになった。This paper is the study about victims' family of the murder case in Ikeda elementary school. The purpose of this study was to explore that what kind of coping behavior and social support. facilitate effective mourning work. In addition, Validity of Lagache hypothesis that a bereaved kills internally a deceased was discussed. It emerged that the mother has generated a love story between her and a deceased daughter through writing memoirs, and her mourning work has facilitated reunion of a bond of affection between them

Morphologic studies of bone marrow cells exposed to the phospholipid fraction from the liver of irradiated animal, an experiment in vitro

With the purpose of revealing the biological effects of the X-ray irradiation the authors extracted phospholipids from the liver of irradiated animals and proved that this substance has the action to inhibit the growth of the bone marrow cells, the motility of pseudo-eosinophilis and the erythropoiesis in tissue culture, suggesting that the injury will mainly be induced by the toxic substances produced by irradiation.</p

X-ray Spectral Study of the extended emission,'the Cap', located 11.6 kpc above the disk of M82

The extended X-ray emission from 'the Cap' region located 11' (11.6 kpc) above the disk of the starburst galaxy M82 has been observed with Suzaku and XMM-Newton. Owing to the good energy resolution and the large collecting area of the XIS on Suzaku, combined with similar properties of the EPIC instrument on XMM-Newton, we have clearly detected K-shell emission lines from O VII, O VIII, Ne X, Mg XI, Mg XII and the Fe-L complex. Two optically-thin thermal plasma components are required to fit the observed X-ray spectra. We have determined the metal abundances of O, Ne, Mg, Si and Fe in this region for the first time. Their metal abundance ratios agree well with those of metal-poor stars and the model prediction of metals synthesized by type-II supernovae, but they are not consistent with the metallicities of type-Ia supernovae. This result is support for the idea that the origin of the metals in the Cap is type-II supernovae explosions occurring in the starburst regions in the M82 galaxy. We discuss the possible contribution from sputtered dust grains to the metals in the Cap. An emission line consistent with the C VI transition of n=4 to 1 at 0.459 keV is marginally detected, although it is not statistically significant at the 99% confidence level; the presence of this line would suggest charge-exchange processes in the Cap.Comment: 16 pages, 10 figuer

Enhancing evidence-informed policymaking in medicine and healthcare: stakeholder involvement in the Commons Project for rare diseases in Japan

Kogetsu A., Isono M., Aikyo T., et al. Enhancing evidence-informed policymaking in medicine and healthcare: stakeholder involvement in the Commons Project for rare diseases in Japan. Research Involvement and Engagement 9, 107 (2023); https://doi.org/10.1186/s40900-023-00515-5.Background: Although stakeholder involvement in policymaking is attracting attention in the fields of medicine and healthcare, a practical methodology has not yet been established. Rare-disease policy, specifically research priority setting for the allocation of limited research resources, is an area where evidence generation through stakeholder involvement is expected to be effective. We generated evidence for rare-disease policymaking through stakeholder involvement and explored effective collaboration among stakeholders. Methods: We constructed a space called ‘Evidence-generating Commons’, where patients, family members, researchers, and former policymakers can share their knowledge and experiences and engage in continual deliberations on evidence generation. Ten rare diseases were consequently represented. In the ‘Commons’, 25 consecutive workshops were held predominantly online, from 2019 to 2021. These workshops focused on (1) clarification of difficulties faced by rare-disease patients, (2) development and selection of criteria for priority setting, and (3) priority setting through the application of the criteria. For the first step, an on-site workshop using sticky notes was held. The data were analysed based on KJ method. For the second and third steps, workshops on specific themes were held to build consensus. The workshop agendas and methods were modified based on participants’ feedback. Results: The ‘Commons’ was established with 43 participants, resulting in positive effects such as capacity building, opportunities for interactions, mutual understanding, and empathy among the participants. The difficulties faced by patients with rare diseases were classified into 10 categories. Seven research topics were identified as priority issues to be addressed including ‘impediments to daily life’, ‘financial burden’, ‘anxiety’, and ‘burden of hospital visits’. This was performed by synthesising the results of the application of the two criteria that were particularly important to strengthen future research on rare diseases. We also clarified high-priority research topics by using criteria valued more by patients and family members than by researchers and former policymakers, and criteria with specific perspectives. Conclusion: We generated evidence for policymaking in the field of rare diseases. This study’s insights into stakeholder involvement can enhance evidence-informed policymaking. We engaged in comprehensive discussions with policymakers regarding policy implementation and planned analysis of the participants’ experiences in this project

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