胃がん術後患者の身体症状とセルフケア能力の関連

本研究は，胃切除術後患者の身体症状とセルフケア能力との関係を明らかにすることを目的とした．Ａ大学病院外来通院中の胃切除術後患者57名を対象に，上部消化管がん患者の術後機能障害を査定する尺度及びセルフケア能力尺度を用いた無記名の自記式質問紙調査を実施した．有効回答は51部であった．術後に頻繁に生じていた身体症状は下痢障害19名（37.0％），活動力障害18名（35.0％）の順に多かった．セルフケア能力は，健康に関心を向ける能力，体調を整える能力が高かった．セルフケア能力と術後身体症状との関連は，健康のために選択する能力（rs ＝－ .34；p ＜ .05），生活を続ける能力（rs ＝－ .32；p ＜ .05），支援してくれる人をもつ能力（rs ＝－ .42；p ＜ .01）の得点がそれぞれ高いほど，活動力障害の得点は有意に低かった．胃がん術後患者が困難を抱える身体症状を軽減するためには，患者が自身のライフスタイルに合った健康管理方法を見つけ，それを選択し，継続して実施していけるようにセルフケア支援を行う必要性が示唆された．そのためには，患者個々の背景をふまえ，術後予測される症状を早期から説明し，入院前外来から退院後にかけて長期間にわたり継続したセルフケア支援を行うことが必要である．The objective of this study was to clarify the relationship between physical symptoms and self-care ability of postgastrectomy patients. Fifty-seven post-gastrectomy patients attending the outpatient clinic of the Department of General Surgery at the A University Hospital underwent an anonymous self-administered questionnaire survey regarding postoperative physical symptoms and self-care abilities. The number of valid responses was 51. In postoperative physical symptoms, frequency of diarrhea disorder and activity disorder were high. In self-care ability, “ability to pay attention to health” and “ability to regulate physical condition” were high. In order to alleviate the physical symptoms that patients have after gastric cancer surgery, it may be necessary to provide self-care support so that patients themselves can find a health management method that suits their lifestyle, and continue to implement it. To that end, based on the patient's background, the symptoms predicted after surgery should be explained to them from an early stage. It is necessary to provide continuous self-care support for a long period from pre-admission outpatient to after discharge

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

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Permeation of Buprenorphine and Its 3-Alkyl-Ester Prodrugs Through Human Skin

Purpose . Homologous 3-alkyl-ester prodrugs (C 2 to C 4 ) of buprenorphine with decreased crystallinity have been synthesized and evaluated for transdermal delivery commensurate with opioid dependence treatment.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41449/1/11095_2004_Article_306751.pd

Association of single nucleotide polymorphisms in the NRF2 promoter with vascular stiffness with aging.

PURPOSE:Pulse wave velocity (PWV), an indicator of vascular stiffness, increases with age and is increasingly recognized as an independent risk factor for cardiovascular disease (CVD). Although many mechanical and chemical factors underlie the stiffness of the elastic artery, genetic risk factors related to age-dependent increases in PWV in apparently healthy people are largely unknown. The transcription factor nuclear factor E2 (NF-E2)-related factor 2 (Nrf2), which is activated by unidirectional vascular pulsatile shear stress or oxidative stress, regulates vascular redox homeostasis. Previous reports have shown that a SNP in the NRF2 gene regulatory region (-617C>A; hereafter called SNP-617) affects NRF2 gene expression such that the minor A allele confers lower gene expression compared to the C allele, and it is associated with various diseases, including CVD. We aimed to investigate whether SNP-617 affects vascular stiffness with aging in apparently healthy people. METHODS:Analyzing wide-ranging data obtained from a public health survey performed in Japan, we evaluated whether SNP-617 affected brachial-ankle PWV (baPWV) in never-smoking healthy subjects (n = 642). We also evaluated the effects of SNP-617 on other cardiovascular and blood test measurements. RESULTS:We have shown that not only AA carriers (n = 55) but also CA carriers (n = 247) show arterial stiffness compared to CC carriers (n = 340). Furthermore, SNP-617 also affected blood pressure indexes such as systolic blood pressure and mean arterial pressure but not the ankle brachial pressure index, an indicator of atherosclerosis. Multivariate analysis showed that SNP-617 accelerates the incremental ratio of baPWV with age. CONCLUSIONS:This study is the first to show that SNP-617 affects the age-dependent increase in vascular stiffness. Our results indicate that low NRF2 activity induces premature vascular aging and could be targeted for the prevention of cardiovascular diseases associated with aging

Reference Values for Weight Loss During 1 Year After Sleeve Gastrectomy : a Multicenter Retrospective Study in Japan.

Introduction:This study aimed to provide reference values for the percentage total weight loss during 1 year after laparoscopic sleeve gastrectomy associated with primary response in Japan.Methods:This multicenter retrospective study comprised 248 patients with severe obesity who underwent laparoscopic sleeve gastrectomy at five institutions in Japan. A percentage total weight loss < 20% at 1 year was defined as primary non-response. Parsimonious predictive models were developed based on the results of multiple regression analyses. A receiver operating characteristic curve analysis was used to assess the discriminative performance for primary non-response.Results:The median age, initial body mass index, and percentage total weight loss at 1 year were 41 years, 41.4 kg/m2, and 30.1%, respectively. There were 28 (11.3%) primary non-responders. For discriminating primary non-responders, the areas under the receiver operating characteristic curve of the parsimonious model and actual percentage of total weight loss at 3 months after laparoscopic sleeve gastrectomy were 0.846 and 0.803, respectively. Cutoffs for the predicted percentage total weight loss using the model and actual value of percentage total weight loss at 3 months attaining 80% sensitivity were 30% and 22%, and those attaining 98% specificity were 22% and 15%, respectively.Conclusions:Reference values for the percentage total weight loss at 3 months were obtained using the predictive model and actual value of percentage total weight loss at 3 months. Patients at risk for primary non-response can be determined at 3 months with these values, which can help in considering earlier interventions