Usefulness of a new DUV-LED device for the control of infection by Escherichia coli, Staphylococcus aureus, mycobacteria and spore-forming bacteria

Reliable disinfection and sterilization technologies are needed to deal with the various infectious diseases spreading around the world. Furthermore, bacteria that are difficult to eliminate by ordinary disinfection are also a problem in the medical environment. We examined the germicidal effect of a newly developed deep-ultraviolet light-emitting diode (DUV-LED) prototype device (wavelength of 280 ± 5 nm; power of 0.9 to 1.4 mW/cm2) for floor sterilization against Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), Mycobacterium gordonae (M. gordonae), and Bacillus subtilis (B. subtilis). This prototype device is equipped with highly practical DUV-LEDs with a high output efficiency and a long life, and was designed with consideration of the irradiation distance and the angle of the DUV-LEDs to provide a uniform irradiation rate. We found a statistically significant reduction of ≥90% in the infectious titers of both E. coli and S. aureus after irradiation for 2 s. Although acid-fast bacilli and spore-type bacilli are generally thought to be resistant to UV light irradiation compared to general bacteria, the acid-fast bacillus M. gordonae was inactivated after irradiation for 10 s, and spore-type cells of the bacillus B. subtilis were inactivated by ≥90% after irradiation for 30 s. We also found that the effects were cumulative when irradiation was performed at intervals. In the future, the usefulness of this device as an infection control measure will be evaluated in daily medical practice

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

線維性過敏性肺炎診断に有用な新たなHRCT所見 “hexagonal pattern”

熊本大

Mental health among older adults in Japan: do sources of social support and negative interaction make a difference?

This study addresses the question of whether social support and interpersonal strain from different sources (i.e., spouse, children, and other relatives and friends) have differential impact on mental health. Data for this research came from a national probability sample of 2200 persons aged 60 and over in Japan. Structural equation models were evaluated within the context of two types of social networks: (a) persons who had a spouse and children (n=1299), and (b) those with children only (n=677). Between these two networks, the links among social support, negative relations, and mental health were contrasted. The effects of various sources of social support and negative interactions on mental health vary depending on the specific dimension of mental health as well as the nature of social networks. Among older Japanese who are married with children, social support from spouse has a greater association with positive well-being than social support from children and others. However, cognitive functioning is uncorrelated with all sources of positive and negative social exchanges. In contrast, among those without a spouse, only greater support from children is significantly correlated with higher positive well-being, less distress, and less cognitive impairment.Social support Negative relations Mental health Japan Older adults

Rapid Inactivation of SARS-CoV-2 Variants by Continuous and Intermittent Irradiation with a Deep-Ultraviolet Light-Emitting Diode (DUV-LED) Device

More than 1 year has passed since social activities have been restricted due to the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). More recently, novel SARS-CoV-2 variants have been spreading around the world, and there is growing concern that they may have higher transmissibility and that the protective efficacy of vaccines may be weaker against them. Immediate measures are needed to reduce human exposure to the virus. In this study, the antiviral efficacy of deep-ultraviolet light-emitting diode (DUV-LED) irradiation (280 ± 5 nm, 3.75 mW/cm2) against three SARS-CoV-2 variants was evaluated. For the B.1.1.7, B.1.351, and P.1 variant strains, irradiation of the virus stocks for 1 s resulted in infectious titer reduction rates of 96.3%, 94.6%, and 91.9%, respectively, and with irradiation for 5 s, the rates increased to 99.9%, 99.9%, and 99.8%, respectively. We also tested the effect of pulsed DUV-LED irradiation (7.5 mW/cm2, duty rate: 50%, frequency: 1 kHz) under the same output conditions as for continuous irradiation and found that the antiviral efficacy of pulsed and continuous irradiation was the same. These findings suggest that by further developing and optimizing the DUV-LED device to increase its output, it may be possible to instantly inactivate SARS-CoV-2 with DUV-LED irradiation

The impact of factor Xa inhibitors on bleeding risk in patients with respiratory diseases

Abstract It is unclear which factor Xa (FXa) inhibitors are associated with higher bleeding risk in patients with respiratory diseases, and there are no studies on the association between prothrombin time–international normalized ratio (PT–INR) and bleeding risk. We conducted a retrospective cohort study comparing 1-year-outcomes and PT–INR between patients with respiratory diseases treated with rivaroxaban (R group, n = 82) or edoxaban (E group, n = 138) for atrial fibrillation or venous thromboembolism from 2013 to 2021. The most frequent event of all bleeding discontinuations was respiratory bleeding in both groups (7.3 and 4.3%, respectively). The cumulative incidence of bleeding discontinuation was significantly higher in the R group (25.6%) than in the E group (14.4%) (hazard ratio [HR], 2.29; 95% confidence interval [CI] 1.13–4.64; P = 0.023). PT–INR after initiation of therapy significantly increased and was higher in the R group than in the E group (median value, 1.4 and 1.2, respectively; P < 0.001). Multivariate analysis using Cox proportional hazards and Fine-Gray models revealed that PT–INR after initiation of therapy was an independent risk factor of bleeding discontinuation events (HR = 4.37, 95% CI 2.57–7.41: P < 0.001). Respiratory bleeding occasionally occurs in patients receiving FXa inhibitors, and monitoring the PT–INR may need to ensure safety

Rapidly progressive interstitial lung disease due to anti-MDA-5 antibody-positive clinically amyopathic dermatomyositis complicated with cervical cancer: Successful treatment with direct hemoperfusion using polymyxin B-immobilized fiber column therapy

The anti-melanoma differentiation-associated gene 5 (MDA-5) antibody is a marker of clinically amyopathic dermatomyositis (CADM) and rapidly progressive interstitial lung disease (ILD) with acute respiratory failure. A 35-year-old woman with cervical cancer showed Gottron's papules, severe hypoxemia, and diffuse ground-glass opacities on chest computed tomography. She was diagnosed with rapidly progressive ILD associated with CADM. Her serum was positive for the anti-MDA-5 antibody. Combination therapy with corticosteroids, immunosuppressants, and direct hemoperfusion using polymyxin B-immobilized fiber column (PMX-DHP) improved her respiratory dysfunction. Eventually, surgery for the cancer was performed successfully. This is the first case to demonstrate the efficacy of PMX-DHP for rapidly progressive ILD with anti-MDA-5 antibody-positive CADM and a malignancy

Image_1_Usefulness of a new DUV-LED device for the control of infection by Escherichia coli, Staphylococcus aureus, mycobacteria and spore-forming bacteria.TIFF

Reliable disinfection and sterilization technologies are needed to deal with the various infectious diseases spreading around the world. Furthermore, bacteria that are difficult to eliminate by ordinary disinfection are also a problem in the medical environment. We examined the germicidal effect of a newly developed deep-ultraviolet light-emitting diode (DUV-LED) prototype device (wavelength of 280 ± 5 nm; power of 0.9 to 1.4 mW/cm2) for floor sterilization against Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), Mycobacterium gordonae (M. gordonae), and Bacillus subtilis (B. subtilis). This prototype device is equipped with highly practical DUV-LEDs with a high output efficiency and a long life, and was designed with consideration of the irradiation distance and the angle of the DUV-LEDs to provide a uniform irradiation rate. We found a statistically significant reduction of ≥90% in the infectious titers of both E. coli and S. aureus after irradiation for 2 s. Although acid-fast bacilli and spore-type bacilli are generally thought to be resistant to UV light irradiation compared to general bacteria, the acid-fast bacillus M. gordonae was inactivated after irradiation for 10 s, and spore-type cells of the bacillus B. subtilis were inactivated by ≥90% after irradiation for 30 s. We also found that the effects were cumulative when irradiation was performed at intervals. In the future, the usefulness of this device as an infection control measure will be evaluated in daily medical practice.</p