Shinmi (親身): a distinctive Japanese medical virtue?

In Western countries, the ideal professional and ethical attributes of healthcare providers and the ideal patient-doctor relationship have been analysed in detail. Other cultures, however, may have different norms, arising in response to diverse healthcare needs, cultural values and offering alternative perspectives. In this paper, drawing a case study, we introduce the concept of Shinmi, used in Japan to describe a desirable approach to medical care. Shinmi means kind or cordial in Japanese. In the medical context, it refers to doctors treating patients with a degree of emotional closeness as if they were the doctors’ own family. We analyse the concept of Shinmi, drawing on virtue ethics. We distinguish two different elements to a Shinmi-na attitude. As illustrated in our example, excessive Shinmi can be problematic for patients and doctors. Furthermore, elements of Shinmi may conflict with existing Western values (for example, norms that encourage emotional detachment and discourage doctors’ treatment of family members). However, if pursued appropriately, we argue that a balanced Shinmi-na approach can be conducive to the goals of medicine. The concept of Shinmi may be valuable for medical students, in Japanese and potentially other health care systems, and help them to cultivate a virtuous approach to meeting the emotional needs of patients

Beliefs held by breast surgeons that impact the treatment decision process for advanced breast cancer patients : a qualitative study

Introduction: Although guidelines do not recommend chemotherapy for patients with advanced cancer when death is imminent, many reports suggest the tendency to continue this treatment has been increasing every year. This study aimed to construct a model to clarify the beliefs and communication of doctors who administer chemotherapy to patients with recurrent or metastatic (hereafter, “recurrent/metastatic”) breast cancer, and determine how these beliefs are related to the process of treating patients. Materials and methods: Semi-structured interviews were conducted with 21 breast surgeons, and interview contents were analyzed using the grounded theory approach in order to conceptualize the treatment process. Results: The process of chemotherapy for patients with recurrent/metastatic breast cancer differed based on two beliefs held by doctors. One was a “belief that the patient is an entity who cannot accept death,” and throughout the treatment process, these doctors consistently avoided sharing bad news that might hurt patients, and always discussed aggressive chemotherapy. They proposed treatments as long as options remained, and when they ultimately judged that the physical condition of patients could not withstand further treatment, treatment was terminated despite the patient hoping for continuation. The other was a “belief that the patient is an entity who can accept death.” From early on after recurrence/metastasis, these doctors repeatedly gave patients information including bad news about prognosis, and when they judged that further treatment would hinder a patient’s ability to have a good death, they proposed terminating treatment. Conclusion: We demonstrated that breast surgeons treating recurrent/metastatic breast cancer patients have two beliefs and constructed a model of the treatment process based on those beliefs. This offered breast surgeons, who make decisions regarding treatment without clearly-defined guidelines, a chance to reflect on their own care style, which we believe will contribute to optimal patient care

Discrimination of Dormant and Active Hematopoietic Stem Cells by G₀ Marker Reveals Dormancy Regulation by Cytoplasmic Calcium

Quiescent hematopoietic stem cells (HSCs) are typically dormant, and only a few quiescent HSCs are active. The relationship between “dormant” and “active” HSCs remains unresolved. Here we generate a G0 marker (G0M) mouse line that visualizes quiescent cells and identify a small population of active HSCs (G0Mlow), which are distinct from dormant HSCs (G0Mhigh), within the conventional quiescent HSC fraction. Single-cell RNA-seq analyses show that the gene expression profiles of these populations are nearly identical but differ in their Cdk4/6 activity. Furthermore, high-throughput small-molecule screening reveals that high concentrations of cytoplasmic calcium ([Ca2+]c) are linked to dormancy of HSCs. These findings indicate that G0M separates dormant and active adult HSCs, which are regulated by Cdk4/6 and [Ca2+]c. This G0M mouse line represents a useful resource for investigating physiologically important stem cell subpopulations

Discrimination of Dormant and Active Hematopoietic Stem Cells by G₀ Marker Reveals Dormancy Regulation by Cytoplasmic Calcium

Quiescent hematopoietic stem cells (HSCs) are typically dormant, and only a few quiescent HSCs are active. The relationship between “dormant” and “active” HSCs remains unresolved. Here we generate a G0 marker (G0M) mouse line that visualizes quiescent cells and identify a small population of active HSCs (G0Mlow), which are distinct from dormant HSCs (G0Mhigh), within the conventional quiescent HSC fraction. Single-cell RNA-seq analyses show that the gene expression profiles of these populations are nearly identical but differ in their Cdk4/6 activity. Furthermore, high-throughput small-molecule screening reveals that high concentrations of cytoplasmic calcium ([Ca2+]c) are linked to dormancy of HSCs. These findings indicate that G0M separates dormant and active adult HSCs, which are regulated by Cdk4/6 and [Ca2+]c. This G0M mouse line represents a useful resource for investigating physiologically important stem cell subpopulations

Update on the hyper immunoglobulin M syndromes

The Hyper-immunoglobulin M syndromes (HIGM) are a heterogeneous group of genetic disorders resulting in defects of immunoglobulin class switch recombination (CSR), with or without defects of somatic hypermutation (SHM). They can be classified as defects of signalling through CD40 causing both a humoral immunodeficiency and a susceptibility to opportunistic infections, or intrinsic defects in B cells of the mechanism of CSR resulting in a pure humoral immunodeficiency. A HIGM picture can also be seen as part of generalized defects of DNA repair and in antibody deficiency syndromes, such as common variable immunodeficiency. CD40 signalling defects may require corrective therapy with bone marrow transplantation. Gene therapy, a potential curative approach in the future, currently remains a distant prospect. Those with a defective CSR mechanism generally do well on immunologoblulin replacement therapy. Complications may include autoimmunity, lymphoid hyperplasia and, in some cases, a predisposition to lymphoid malignancy

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

Postulated Vasoactive Neuropeptide Autoimmunity in Fatigue-Related Conditions: A Brief Review and Hypothesis

Disorders such as chronic fatigue syndrome (CFS) and gulf war syndrome (GWS) are characterised by prolonged fatigue and a range of debilitating symptoms of pain, intellectual and emotional impairment, chemical sensitivities and immunological dysfunction. Sudden infant death syndrome (SIDS) surprisingly may have certain features in common with these conditions. Post-infection sequelae may be possible contributing factors although ongoing infection is unproven. Immunological aberration may prove to be associated with certain vasoactive neuropeptides (VN) in the context of molecular mimicry, inappropriate immunological memory and autoimmunity

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

Search for H→γγ produced in association with top quarks and constraints on the Yukawa coupling between the top quark and the Higgs boson using data taken at 7 TeV and 8 TeV with the ATLAS detector

A search is performed for Higgs bosons produced in association with top quarks using the diphoton decay mode of the Higgs boson. Selection requirements are optimized separately for leptonic and fully hadronic final states from the top quark decays. The dataset used corresponds to an integrated luminosity of 4.5 fb−14.5 fb−1 of proton–proton collisions at a center-of-mass energy of 7 TeV and 20.3 fb−1 at 8 TeV recorded by the ATLAS detector at the CERN Large Hadron Collider. No significant excess over the background prediction is observed and upper limits are set on the tt¯H production cross section. The observed exclusion upper limit at 95% confidence level is 6.7 times the predicted Standard Model cross section value. In addition, limits are set on the strength of the Yukawa coupling between the top quark and the Higgs boson, taking into account the dependence of the tt¯H and tH cross sections as well as the H→γγ branching fraction on the Yukawa coupling. Lower and upper limits at 95% confidence level are set at −1.3 and +8.0 times the Yukawa coupling strength in the Standard Model

2018年度読書運動プロジェクト活動報告書

活動資料 p.(1)～p.(5)はじめに : 藤本 朝巳 p.1読書会 : 小根山 桃子、立原 優菜、三雲 紫恩 p.2-p.4コンテスト・コンクール : 森園 佳子 p.5-p.7展示 : 山下 萌 p.8-p.11コラボランチ : 社本 衣舞紀 p.12文学散歩 : 中村 好花 p.13選書ツアー : 津田 優里香、鈴木 綾紗 p.14-p.15泉区読書推進イベント : 森園 佳子、伊豆 美保、小林 すずな p.16-p.18絵本講座・読み聞かせ講座 : 森園 佳子 p.19大学祭 : 花房 若奈、林 陽子 p.20-p.22朗読会 : 小野 紘子、関口 恵奈、穂積 優香、三雲 紫恩、児玉 玲奈、平山 真由子、宇野 菜々春、小林 すずな p.23-p.29プロフィール : p.30-39おわりに : 森園 佳子 p.40写真あり表あ