Polypharmacy, Potentially Inappropriate Medications, and Dysphagia in Older Inpatients: A Multi-Center Cohort Study

Background Although the relationship between medication status, symptomatology, and outcomes has been evaluated, data on the prevalence of polypharmacy and potentially inappropriate medications (PIMs) and the association of polypharmacy and PIMs with swallowing function during follow-up are limited among hospitalized patients aged ≥65 years with dysphagia. Methods In this 19‐center cohort study, we registered 467 inpatients aged ≥65 years and evaluated those with the Food Intake LEVEL Scale (FILS) scores ≤8 between November 2019 and March 2021. Polypharmacy was defined as prescribing ≥5 medications and PIMs were identified based on the 2023 Updated Beers Criteria. We applied a generalized linear regression model to examine the association of polypharmacy and PIMs with FILS score at discharge. Results We analyzed 399 participants (median age, 83.0 years; males, 49.8%). The median follow‐up was 51.0 days (interquartile range, 22.0–84.0 days). Polypharmacy and PIMs were present in 67.7% of and 56.1% of patients, respectively. After adjusting for covariates, neither polypharmacy (β = 0.05; 95% confidence interval [CI], -0.04–0.13, p=0.30) nor non‐steroidal anti‐inflammatory medications (β = 0.09; 95% CI, -0.02–0.19; p=0.10) were significantly associated with FILS score at discharge. Conclusions The results of this study indicated a high proportion of polypharmacy and PIMs among inpatients aged ≥65 years with dysphagia. Although these prescribed conditions were not significantly associated with swallowing function at discharge, our findings suggest the importance of regularly reviewing medications to ensure the appropriateness of prescriptions when managing older inpatients

Microbiological Investigation of the Iron-Containing Floculent Mats in Various Deep Sea Environments

Conference abstract (August 14-19, 2011, Goldschmidt 2011 in Prague, Czech Republic)http://www.godac.jamstec.go.jp/darwin/cruise/natsushima/nt10-13_leg2/ehttp://www.godac.jamstec.go.jp/darwin/cruise/yokosuka/yk10-10/

IL-6 receptor antibody treatment improves muscle weakness in experimental autoimmune myasthenia gravis mouse model

Myasthenia gravis (MG) is a chronic autoimmune disease characterized by muscle weakness and fatigue. It is caused by pathological autoantibodies against components expressed at neuromuscular junctions, such as acetylcholine receptor (AChR). Interleukin-6 (IL-6) has been suggested to play a role in the pathogenesis of MG, and IL-6 receptor (IL-6R) antibody treatment may provide a novel therapeutic option. In this study, we investigated the effects of IL-6R antibody treatment in an experimental autoimmune MG (EAMG) mouse model. We demonstrated that IL-6R antibody treatment improved muscle weakness, reduced IgG deposition at neuromuscular junctions, and the levels of AChR autoantibodies in serum. In addition, follicular helper T cells and Th17, plasma cells in lymph nodes were lower in IL-6R antibody treated mice. Our findings suggest that IL-6R blockade may be a novel and effective therapeutic strategy for the treatment of MG

Azilsartan inhibits inflammation-triggered bone resorption and osteoclastogenesis in vivo via suppression of TNF-α expression in macrophages

IntroductionHypertension is a major risk factor for cardiovascular disease (CVD) and is associated with increased bone loss due to excessive activity of the local renin-angiotensin system (RAS). Angiotensinogen/Angiotensin (ANG) II/Angiotensin II type 1 receptor (AT1R) axis is considered as the core axis regulating RAS activity. Azilsartan is an FDA-approved selective AT1R antagonist that is used to treat hypertension. This study aimed to determine whether azilsartan affects formation of osteoclast, resorption of bone, and the expression of cytokines linked with osteoclastogenesis during lipopolysaccharide (LPS)-triggered inflammation in vivo.MethodsIn vivo, following a 5-day supracalvarial injection of LPS or tumor necrosis factor-alpha (TNF-α) with or without azilsartan, the proportion of bone resorption and the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells, which are identified as osteoclasts on mice calvariae were counted. The mRNA expression levels of TRAP, cathepsin K, receptor activator of NF-κB ligand (RANKL), and TNF-α were also evaluated. In vitro, the effect of azilsartan (0, 0.01, 0.1, 1, and 10 μM) on RANKL and TNF-α-triggered osteoclastogenesis were investigated. Also, whether azilsartan restrains LPS-triggered TNF-α mRNA and protein expression in macrophages and RANKL expression in osteoblasts were assessed. Furthermore, western blotting for analysis of mitogen-activated protein kinases (MAPKs) signaling was conducted.ResultsAzilsartan-treated calvariae exhibited significantly lower bone resorption and osteoclastogenesis than those treated with LPS alone. In vivo, LPS with azilsartan administration resulted in lower levels of receptor activator of RANKL and TNF-α mRNA expression than LPS administration alone. Nevertheless, azilsartan did not show inhibitory effect on RANKL- and TNF-α-triggered osteoclastogenesis in vitro. Compared to macrophages treated with LPS, TNF-α mRNA and protein levels were lower in macrophages treated by LPS with azilsartan. In contrast, RANKL mRNA and protein expression levels in osteoblasts were the same in cells co-treated with azilsartan and LPS and those exposed to LPS only. Furthermore, azilsartan suppressed LPS-triggered MAPKs signaling pathway in macrophages. After 5-day supracalvarial injection, there is no difference between TNF-α injection group and TNF-α with azilsartan injection group.ConclusionThese findings imply that azilsartan prevents LPS-triggered TNF-α production in macrophages, which in turn prevents LPS-Triggered osteoclast formation and bone resorption in vivo

The Efficacy of a Bilateral Approach for Treating Lesions With Chronic Total Occlusions The CART (Controlled Antegrade and Retrograde subintimal Tracking) Registry

ObjectivesThe aim of this study was to evaluate the safety and feasibility of a new concept for chronic total occlusion (CTO) recanalization—using a bilateral approach that utilizes a Controlled Antegrade and Retrograde subintimal Tracking (CART) technique.BackgroundSuccessful percutaneous recanalization of coronary CTOs results in improved long-term outcomes. The recanalization of CTOs in native coronary arteries no doubt represents one of the most technically challenging of interventional procedures.MethodsA total of 224 consecutive patients (mean age 61 ± 9 years; 86.2% men) were enrolled in this prospective multicenter registry. This technique combines the simultaneous use of antegrade and retrograde approaches. A subintimal dissection is created in both antegrade and retrograde fashion, thereby limiting the extension of the subintimal dissection within the CTO portion.ResultsOf 224 CTO lesions (>3 months in duration) undergoing attempted recanalization using the CART technique, 145 cases (64.7%) had undergone previous CTO recanalization attempts. The success rates of crossing in a retrograde fashion with a wire and a balloon were 87.9% and 79.9%, respectively. The overall technical and procedural success rates achieved in this registry were 92.4% and 90.6%, respectively.ConclusionsA bilateral approach for CTO lesions using the CART technique is feasible, safe, and has a higher success rate than previous approaches. These results indicate that a bilateral technique can solve a major dilemma that commonly affects CTO procedures

各地の深海底に存在する褐色変色域での微生物調査

BE11-P72ポスター要旨 / ブルーアース2011（2011年3月7日～8日, 東京海洋大学品川キャンパス）http://www.godac.jamstec.go.jp/darwin/cruise/natsushima/nt05-18/ehttp://www.godac.jamstec.go.jp/darwin/cruise/natsushima/nt10-06_leg2/ehttp://www.godac.jamstec.go.jp/darwin/cruise/natsushima/nt10-13_leg2/ehttp://www.godac.jamstec.go.jp/darwin/cruise/yokosuka/yk10-10/

六甲山系の自然と地域特性を活かした高大連携授業に関する研究/総合学習の時間を利用したデザインカリキュラム

本研究は、文部科学省における「高等学校と大学との接続における一人一人の能力を伸ばすための連携（高大連携）の在り方について」の指針に基づいて、本校の位置する六甲山系の自然と地域の特性を活かした高大連携授業の在り方について、実践的活動を通して実地検証していくことを目的とした。　総合学習に於いて実施した科目は以下の通りである。講座①：神戸鈴蘭台高校を「計測」する（長濱・宮本）講座②：使いやすい減災グッズ制作（見寺・野口・ばんば）講座③：自然素材を用いた雑貨制作（大田・相澤・佐野・田頭）講座④：テクノ工作（相良・古賀・逸身・向井・見明）講座⑤：高大連携授業のドキュメンテーションと情報発信（曽和）。　本研究の結果、以下の成果を得た。①高等学校における総合学習に組み入れることにより、年間を通じたプロジェクトを推進するカリキュラムを作成することができた。②文部科学省における「高校生に対して、大学レベルの教育研究に触れる機会の促進」をデザイン教育の視点から取り組むことができた。③地域の特性を活用することで、高大連携を主軸とした、地域のデザイン教育活動の活性化を図ることが可能となった。This research had the purpose of verifying integrated study in high school by making use of regional and natural assets of Mt.Rokko through the activities with high school, based on “Cooperation in order to extend the person\u27s ability in connection with the high school and university” by Ministry of education.The subject of integrated study was;(1)“Measurement” of Kobe Suzurandai High School: NAGAHAMA and MIYAMOTO.(2)Making of useful disaster mitigation goods: MITERA, NOGUCHI and BAMBA.(3)Production of living goods used by natural material: OOTA, AIZAWA, SANO and TAGASHIRA.(4)Craft and Computer Programming: SAGARA, KOGA, ITSUMI, MUKAI and MIAKE.We had the results as follows; (1) We could make the curriculum for a year by based on including the integrated study. (2) We could provide the design subject based on the guideline of Ministry of Education. (3) We could activate the design education using by the character of region

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