The Moment of Establishing Transpersonal Caring in a Grieving Adolescent Daughter beside Her Mother’s Deathbed and Hansen’s Disease Survivors Sharing Their Life Review

Evidence-based nursing (EBN) ensures the science of nursing practice, while the philosophical and ethical aspects of nursing practice are based on caring. Caring not only leads to the patient and their family’s healing but also to the nurse’s professional and personal growth since caring includes mutual approval and reciprocity. In the latter half of the chapter, we explain how to establish Dr. Jean Watson’s transpersonal caring using the following two events: ① case study: An expert nurse unintentionally says, “Your mother continues to be near and protect you,” to a crying daughter beside her mother’s deathbed; and ② our project: sanatorium’s nurses listen to Hansen’s disease survivors’ life review

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

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Niflumic Acid Inhibits Goblet Cell Degranulation in a Guinea Pig Asthma Model

Background: Human Ca2+-activated Cl ion channel 1 (hCLCAl) is expressed in goblet cell hyperplasia in the airway of asthmatics, and murine CLCA3 is associated with antigen-sensitized and IL-13-induced goblet cell metaplasia in mice. However, the role of CLCA in goblet cell degranulation is not fully investigated. Niflumic acid (NFA), a relatively specific CLCA inhibitor, inhibits goblet cell metaplasia, but the effect of NFA on goblet cell degranulation has not been determined in an asthma model. Methods: Guinea pigs were sensitized with ovalbumin (OA) twice and then challenged with saline, OA, histamine, and one of the Ca2+-dependent secretagogues, UTP. The PAS/AB-stained mucus area in the tracheal epithelium was measured with a computer image analysis system, and the morphology of mucus granules was examined by transmission electron microscopy. In the in vitro experiment, goblet cells cultured with IL-13 at the air-liquid interface were stimulated with UTP in the presence or absence of NFA, and the MUC5AC level in cell lysates was measured by ELISA. Results: The mucus areas were smaller in the OA-, histamine-, and UTP-challenged animals than in the saline-challenged animals. NFA inhibited the decrease in mucus area and morphological changes in mucus granules. UTP caused swelling and exocytosis of mucus granules and MUC5AC secretion by cultured goblet cells, and NFA inhibited these changes. Conclusions: NFA inhibited the secretory response of mucus granules in an asthma model, suggesting that CLCA may be associated with goblet cell degranulation and that CLCA inhibitors may be useful for the treatment of hypersecretion in asthma