Stress corrosion cracking of copper in swollen bentonite simulating nuclear waste disposal environment

Stress corrosion cracking (SCC) of pure copper in bentonite clay was examined using a slow strain rate test (SSRT). Bentonite was swollen with pure water or aqueous solutions containing NH₃ of 5 and 10 mM. Thick corrosion films and particulate deposits were formed on the copper surface after the SSRT. Typical tarnish rupture-type SCC occurred on pure copper in swollen bentonite with and without NH₃. The crack propagation rate was enhanced by NH₃. It is confirmed that a thick oxide layer was formed on copper during plastic deformation, resulting in tarnish crack-type SCC. Many particulate deposits observed on the surface were formed due to the rapid dissolution of Cu²⁺ ions to form porous CuO at local deformed sites, regardless of the SCC occurrence

Decreased step count prior to the first visit for MDD treatment: a retrospective, observational, longitudinal cohort study of continuously measured walking activity obtained from smartphones

IntroductionMajor depressive disorder (MDD) is a common debilitating psychiatric condition and a major cause of productivity loss in workers. Using intermittent, subjective indicators, previous studies have shown that physical activity can predict lower levels of depressive symptoms. However, there is an unmet need for continuous and objective measures to identify MDD development before it results in productivity loss. The aim of this study was to elucidate the association between continuously measured walking activity and the development of MDD.MethodsThis retrospective, observational, longitudinal cohort study used health insurance claims data. Individuals aged 20–74 years were included if they had a record of MDD diagnosis and daily step count data for the 60 days before and after the first recorded MDD-related visit, which was defined as the index date. Multivariate analysis was conducted to compare 7-day moving averages of step counts on each day of the analysis period with the mean step count on the index date. Joinpoint regression analysis was used to determine when the trajectory of the moving step count average changed (inflection point).ResultsIn total, 2,143 patients with a mean age of 41.2 (standard deviation [SD]: 10.6) years were included. The majority of patients were men (69.5%) and employed full-time (94.1%). Antidepressants were prescribed for 59.2% of patients. The 7-day moving average step count decreased from 6,310 (SD: 3758) at day −60 to 5,879 (SD: 3183) at the index date (first recorded MDD-related visit), and then increased to 6,062 (SD: 4029) at day +60. Compared with the index date, the 7-day moving average of step counts was significantly higher at days −60 to −1, +23 to +33, and + 42 to +60, and significantly lower at days +2 and + 3. Joinpoint regression analysis of 7-day moving average step counts from day −60 to day 0 identified an inflection point at day −14.ConclusionIn working-age Japanese people, a formal diagnosis of MDD was preceded by a notable decline in daily step counts by approximately 2 weeks. MDD diagnosis and (presumed) treatment were followed by a gradual increase in daily step counts

Attenuation of conduction delay by ischemic preconditioning reduces ischemia-induced ventricular arrhythmias.

Ischemic preconditioning has been acknowledged as a powerful method of decreasing ischemic injury. However, the antiarrhythmic mechanism of ischemic preconditioning during ischemia is unclear. We studied the effects of ischemic preconditioning on arrhythmias and cardiac electrophysiology during ischemia in Langendorff rat hearts (n = 44). In the non-preconditioned group (PC(-); n = 24), the hearts underwent 5-min zero-flow global ischemia without any prior ischemic preconditioning. In the preconditioned group (PC(+); n = 20), the hearts were preconditioned by three cycles of 3-min zero-flow global ischemia and 5-min reperfusion before undergoing 5-min global ischemia. Ischemic preconditioning reduced the incidence of ischemia-induced arrhythmias (PC(-); 38.9%, PC(+): 8.3%, p < 0.05), shortened monophasic action potential duration (MAPD, P < 0.05), attenuated conduction delay (conduction time; PC(-): 234.2%, PC(+): 173.4%, P < 0.05) and increased the ventricular fibrillation threshold. Although the shortening of MAPD in PC(-) hearts was not influenced by the presence or absence of arrhythmias, conduction time prolongation at 3-min was more obvious in PC(-) hearts with arrhythmia than in PC(-) hearts without arrhythmia (PC(-) with arrhythmia: 220.2%, PC(-) without arrhythmia: 190.7%, P < 0.05). We concluded that ischemic preconditioning could protect the rat hearts from ischemia-induced arrhythmias and postulated that attenuation of conduction delay during ischemia might be an important factor in the antiarrhythmic action of ischemic preconditioning.</p

Prevalence and predictors of direct discharge home following hospitalization of patients with serious adverse events managed by the rapid response system in Japan: a multicenter, retrospective, observational study

Aim: The rapid response system (RRS) is an in-hospital medical safety system. To date, not much is known about patient disposition after RRS activation, especially discharge home. This study aimed to investigate the prevalence, characteristics, and outcomes of patients with adverse events who required RRS activation. Methods: Retrospective data from the In-Hospital Emergency Registry in Japan collected from April 2016 to November 2020 were eligible for our analysis. We divided patients into Home Discharge, Transfer, and Death groups. The primary outcome was the prevalence of direct discharge home, and independently associated factors were determined using multivariable logistic regression. Results: We enrolled 2,043 patients who met the inclusion criteria. The prevalence of discharge home was 45.7%; 934 patients were included in the Home Discharge group. Age (adjusted odds ratio [AOR] 0.96; 95% confidence interval [CI], 0.95-0.97), malignancy (AOR 0.69; 95% CI, 0.48-0.99), oxygen administration before RRS (AOR 0.49; 95% CI, 0.36-0.66), cerebral performance category score on admission (AOR 0.38; 95% CI, 0.26-0.56), do not attempt resuscitation order before RRS (AOR 0.17; 95% CI, 0.10-0.29), RRS call for respiratory failure (AOR 0.50; 95% CI, 0.34-0.72), RRS call for stroke (AOR 0.12; 95% CI, 0.03-0.37), and intubation (AOR 0.20; 95% CI, 0.12-0.34) were independently negative, and RRS call for anaphylaxis (AOR 15.3; 95% CI, 2.72-86.3) was positively associated with discharge home. Conclusion: Less than half of the in-hospital patients under RRS activation could discharge home. Patients' conditions before RRS activation, disorders requiring RRS activation, and intubation were factors that affected direct discharge home

Inhibition of Hepatitis C Virus Replication and Viral Helicase by Ethyl Acetate Extract of the Marine Feather Star Alloeocomatella polycladia

Hepatitis C virus (HCV) is a causative agent of acute and chronic hepatitis, leading to the development of hepatic cirrhosis and hepatocellular carcinoma. We prepared extracts from 61 marine organisms and screened them by an in vitro fluorescence assay targeting the viral helicase (NS3), which plays an important role in HCV replication, to identify effective candidates for anti-HCV agents. An ethyl acetate-soluble fraction of the feather star Alloeocomatella polycladia exhibited the strongest inhibition of NS3 helicase activity, with an IC50 of 11.7 µg/mL. The extract of A. polycladia inhibited interaction between NS3 and RNA but not ATPase of NS3. Furthermore, the replication of the replicons derived from three HCV strains of genotype 1b in cultured cells was suppressed by the extract with an EC50 value of 23 to 44 µg/mL, which is similar to the IC50 value of the NS3 helicase assay. The extract did not induce interferon or inhibit cell growth. These results suggest that the unknown compound(s) included in A. polycladia can inhibit HCV replication by suppressing the helicase activity of HCV NS3. This study may present a new approach toward the development of a novel therapy for chronic hepatitis C

Utility and safety of a new uneven double-lumen sphincterotome in cases of difficult biliary cannulation.

Background:We investigated the utility and safety of a new uneven double-lumen sphincterotome in biliary cannulation in comparison with the conventional pancreatic guidewire (PGW) method.Methods:We retrospectively evaluated 119 patients who required PGW placement because of difficult biliary cannulation. Endoscopic retrograde cholangiopancreatography (ERCP) was performed using a conventional ERCP catheter or a new uneven double-lumen sphincterotome. The success rate of bile duct cannulation, the operation time of bile duct cannulation, and the incidence of post-ERCP pancreatitis (PEP) were evaluated.Results:Forty-four patients were treated with a new double-lumen sphincterotome (the new sphincterotome group) and 75 patients underwent conventional PGW placement (the conventional group). The success rate of bile duct cannulation was 39/44 (88.6%) in the new sphincterotome group and 63/75 (84.0%) in the conventional group (not significant). The total biliary cannulation time (from the reach to the papilla to the finish of biliary cannulation) was 16.0 (6.5-78) min in the new sphincterotome group and 26.0 (5-80) min in the conventional group (P < 0.01). The time from PGW placement to bile duct cannulation was 3.5 (0.3-57) min in the magictome group and 12.0 (1-65) min in the conventional group (P < 0.01). Hyperamylasemia was observed in 13/44 (29.5%) and 17/75 (22.7%), respectively (not significant). Five of 44 (11.3%) of the new sphincterotome group and 14/75 (18.7%) of the conventional group were diagnosed with PEP (not significant).Conclusion:A new double-lumen sphincterotome allows selective bile duct cannulation to be performed in a shorter time than the conventional PGW method

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