Role of vinculin in paracellular barrier for ions

The paracellular barrier function of tight junctions (TJs) in epithelial cell sheets is robustly maintained against mechanical fluctuations, by molecular mechanisms that are poorly understood. Vinculin is an adaptor of a mechanosensory complex at the adherens junction. Here, we generated vinculin KO Eph4 epithelial cells and analyzed their confluent cell-sheet properties. We found that vinculin is dispensable for the basic TJ structural integrity and the paracellular barrier function for larger solutes. However, vinculin is indispensable for the paracellular barrier function for ions. In addition, TJs stochastically showed dynamically distorted patterns in vinculin KO cell sheets. These KO phenotypes were rescued by transfecting full-length vinculin and by relaxing the actomyosin tension with blebbistatin, a myosin II ATPase activity inhibitor. Our findings indicate that vinculin resists mechanical fluctuations to maintain the TJ paracellular barrier function for ions in epithelial cell sheets

Real-time In Situ Electron Spin Resonance Measurements on Fungal Spores of Penicillium digitatum during Exposure of Oxygen Plasmas

We report the kinetic analysis of free radicals on fungal spores of Penicillium digitatum interacted with atomic oxygen generated plasma electric discharge using real time in situ electron spin resonance (ESR) measurements. We have obtained information that the ESR signal from the spores was observed and preliminarily assignable to semiquinone radical with a g-value of around 2.004 and a line width of approximately 5G. The decay of the signal is possibly linked to the inactivation of the fungal spore. The real-time in situ ESR has proven to be a useful method to elucidate plasma-induced surface reactions on biological specimens.Comment: 11 pages, 5 figure

Elevated Fasting Blood Glucose Levels Are Associated With Lower Cognitive Function, With a Threshold in Non-Diabetic Individuals: A Population-Based Study.

BACKGROUND:Cognitive dysfunction has been recognized as a diabetes-related complication. Whether hyperglycemia or elevated fasting glucose are associated with cognitive decline remains controversial. We aimed to investigate the relationship between fasting glucose levels and cognitive function in diabetic and non-diabetic individuals.METHODS:Participants were Japanese diabetic (n = 191) and non-diabetic (n = 616) men, aged 46-81 years, from 2010-2014. Blood samples were taken after a 12 h fast. The Cognitive Ability Screening Instrument (CASI), with a maximum score of 100, was used for cognitive assessment. Cognitive domains of CASI were also investigated. Fractional logit regression with covariate adjustment for potential confounders was used to model cross-sectional relationships between fasting blood glucose and CASI score.RESULTS:For diabetic individuals, CASI score was 0.38 (95% confidence interval: 0.66-0.12) lower per 1 mmol/L higher fasting glucose level. Short-term memory domain also exhibited an inverse association. For non-diabetic individuals, a reverse U-shaped relationship was observed between fasting glucose and cognitive function, identifying a threshold for highest cognitive performance of 91.8 CASI score at 3.97-6.20 mmol/L (71.5-111.6 mg/dL) fasting glucose. Language ability domain displayed a similar relationship with fasting glucose.CONCLUSIONS:Elevated fasting glucose levels in diabetic men were associated with lower cognitive function, in which short-term memory was the main associated domain. Interestingly, in non-diabetic men, we identified a threshold for the inverse relationship of elevated fasting glucose with cognitive function. Contrastingly to diabetic men, language ability was the main associated cognitive domain among non-diabetic men

Amelioration of prevalence of threatened preterm labor during the COVID-19 pandemic: nationwide database analysis in Japan

We aimed to evaluate the changes in maternal and neonatal complications such as threatened preterm labor (TPL) and preterm birth before and during the coronavirus disease 2019 (COVID-19) pandemic using large-scale real-world data in Japan. We obtained data from the Japan Medical Data Center claims database and evaluated differences in maternal and neonatal complications, such as the prevalence of TPL and preterm birth before the COVID-19 pandemic (in the year 2018 or 2019) and during the COVID-19 pandemic (in 2020). We included 5533, 6257, and 5956 deliveries in the years 2018, 2019, and 2020, respectively. TPL prevalence and preterm birth had significantly decreased in 2020 (41.3%, 2.6%, respectively) compared with those reported in 2018 (45.3%, 3.9%, respectively) and 2019 (44.5%, 3.8%, respectively). Neonatal outcomes such as low-birth-weight infants and retinopathy of prematurity were also improved during the pandemic. There were no clear trends in the prevalence of maternal complications such as hypertensive disorders of pregnancy; hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome; and preeclampsia. Oral ritodrine hydrochloride usage in all participants had significantly decreased during the COVID-19 pandemic. In conclusion, our results suggest that the COVID-19 pandemic has ameliorated TPL and consequently reduced the number of preterm births

Association between Stress-Coping Strategy and Functional Disability in the General Older Adult Population: The Takashima Study.

Background:Both physical and psychological factors have been associated with functional disability. However, the associations between stress-coping strategies and future functional disability remain unclear.Methods:We analyzed 2,924 participants who did not have incidence of functional disability or death within the first 3 years of the baseline survey and were aged 65 years or more at the end of follow-up. Stress-coping strategies were assessed via a self-administered questionnaire (emotional expression, emotional support seeking, positive thought, problem-solving, and disengagement) in a baseline survey from 2006 to 2014. Levels of coping strategies were classified as low, middle, and high based of frequency. Functional disability decline was followed up using the long-term-care insurance program until November 1, 2019. Functional disability decline was defined as a new long-term-care insurance program certification. Cox proportional hazards model with competing risk analysis for death was used to evaluate associations between coping strategy levels and functional disability.Results:During the follow-up period, we observed 341 cases of functional disability and 73 deaths without previous incidence of functional disability. A significant inverse association between "positive thought" and "problem-solving" and future functional disability was observed. Multivariable adjusted hazard ratios (95% confidence interval) for functional disability were 0.68 (0.51-0.92) for high levels of "positive thought" and 0.73 (0.55-0.95) for high levels of "problem-solving," compared with low levels of the coping strategies. The inverse association was stronger in men.Conclusions:Some subcomponents of stress-coping strategies might be associated with future incidence of functional disability among older adults

Long-Term Survival after Stroke in 1.4 Million Japanese Population : Shiga Stroke and Heart Attack Registry.

Background and Purpose:Although numerous measures for stroke exist, stroke remains one of the leading causes of death in Japan. In this study, we aimed to determine the long-term survival rate after first-ever stroke using data from a large-scale population-based stroke registry study in Japan.Methods:Part of the Shiga Stroke and Heart Attack Registry, the Shiga Stroke Registry is an ongoing population-based registry study of stroke, which covers approximately 1.4 million residents of Shiga Prefecture in Japan. A total 1,880 patients with non-fatal first-ever stroke (among 29-day survivors after stroke onset) registered in 2011 were followed up until December 2016. Five-year cumulative survival rates were estimated using the Kaplan-Meier method, according to subtype of the index stroke. Cox proportional hazards models were used to assess predictors of subsequent all-cause death.Results:During an average 4.3-year follow-up period, 677 patients died. The 5-year cumulative survival rate after non-fatal first-ever stroke was 65.9%. Heterogeneity was present in 5-year cumulative survival according to stroke subtype: lacunar infarction, 75.1%; large-artery infarction, 61.5%; cardioembolic infarction, 44.9%; intracerebral hemorrhage, 69.1%; and subarachnoid hemorrhage, 77.9%. Age, male sex, Japan Coma Scale score on admission, and modified Rankin Scale score before stroke onset were associated with increased mortality during the chronic phase of ischemic and hemorrhagic stroke.Conclusions:In this study conducted in a real-world setting of Japan, the 5-year survival rate after non-fatal first-ever stroke remained low, particularly among patients with cardioembolic infarction and large-artery infarction in the present population-based stroke registry

Control of Diabetes Mellitus and Long-Term Prognosis in Stroke Patients : The Shiga Stroke and Heart Attack Registry.

Background:The relationship between diabetes control status and long-term prognosis after stroke incidence remains unclear. This study aimed to investigate the effect of diabetes status at admission on long-term survival in patients with first-ever stroke.Methods:A retrospective cohort study was conducted based on the Shiga Stroke and Heart Attack Registry in Japan. Patients were classified according to their diabetes status and glycated hemoglobin (HbA1c) value at hospital admission into the following: (1) free of diabetes (no history of diabetes and HbA1c <6.5%); (2) good control (history of diabetes and HbA1c <7%; free of history and 6.5% ≤HbA1c <7%); and (3) poor control (with or without a history of diabetes and HbA1c ≥7%). Multivariable Cox regression models were used to evaluate the association between diabetes status and long-term survival from stroke onset. Additionally, we also evaluated the association between diabetes status and conditional survival, beginning 29 days after stroke onset.Results:A total of 6,331 first-ever stroke patients were eligible for this study. Among study patients, the mean (±SD) age was 72.85 ± 13.19 years, and the mean (±SD) follow-up year was 2.76 ± 1.66 years; additionally, 42.09% of patients were women. Among patients with all strokes, considering the free-of-diabetes group as the reference group, the adjusted hazard ratio (95% confidence interval) for mortality was 1.26 (1.10, 1.44) in the good control group and 1.22 (1.05, 1.41) in the poor control group. Among patients with ischemic stroke, the adjusted hazard ratio was 1.24 (1.06, 1.46) in good control group and 1.27 (1.08, 1.50) in poor control group. After excluding patients who died within 28 days, the adjusted hazard ratio for conditional mortality in the poor control group was 1.31 (1.12, 1.54) among all stroke patients and 1.29 (1.08, 1.54) among ischemic stroke patients. No significant associations were observed between diabetic status and long-term mortality in intracerebral hemorrhage patients.Conclusions:The findings suggest that first-ever stroke patients with diabetes exhibited a higher risk of all-cause mortality than those without diabetes, particularly in the overall stroke and ischemic stroke populations. Additionally, in stroke populations after 28 days of onset, high risk of long-term mortality was stated in stroke patients with poor HbA1c control

Association of Red Meat Intake with the Risk of Cardiovascular Mortality in General Japanese Stratified by Kidney Function: NIPPON DATA80.

The consumption of red meat has been recommended for individuals with reduced kidney function. However, red meat intake was recently suspected to increase cardiovascular disease (CVD) risk. We evaluated the association of red meat intake with CVD mortality risk in Japanese with/without reduced kidney function. Overall, 9112 participants of a Japanese national survey in 1980, aged ≥30 years, were followed for 29 years. Red meat intake was assessed using weighed dietary record. Cox proportional hazards models were used to estimate the hazard ratio (HR) of CVD mortality according to sex-specific tertiles of red meat intake. We also performed stratified analyses with/without reduced kidney function defined as estimated glomerular filtration rate less than 60 mL/min/1.73 m2. Red meat intake was not associated with CVD mortality risk in men and women. In stratified analyses, the HR of the highest compared with the lowest tertile of red meat intake was lower only in women with reduced kidney function (0.67, 95% confidence interval 0.46-0.98). In conclusion, there were no clear associations between red meat intake and CVD mortality risk in Japanese population; however, a higher intake of red meat was associated with lower risk of future CVD mortality in women with reduced kidney function

Prediction of radiation pneumonitis using dose-volume histogram parameters with high attenuation in two types of cancer: A retrospective study.

The constraint values of dose-volume histogram (DVH) parameters for radiation pneumonitis (RP) prediction have not been uniform in previous studies. We compared the differences between conventional DVH parameters and DVH parameters with high attenuation volume (HAV) in CT imaging in both esophageal cancer and lung cancer patients to determine the most suitable DVH parameters in predicting RP onset. Seventy-seven and 72 patients who underwent radiation therapy for lung cancer and esophageal cancer, respectively, were retrospectively assessed. RP was valued according to the Common Terminology Criteria for Adverse Events. We quantified HAV with quantitative computed tomography analysis. We compared conventional DVH parameters and DVH parameters with HAV in both groups of patients. Then, the thresholds of DVH parameters that predicted symptomatic RP and the differences in threshold of DVH parameters between lung cancer and esophageal cancer patient groups were compared. The predictive performance of DVH parameters for symptomatic RP was compared using the area under the receiver operating characteristic curve. Mean lung dose, HAV30% (the proportion of the lung with HAV receiving ≥30 Gy), and HAV20% were the top three parameters in lung cancer, while HAV10%, HAV5%, and V10 (the percentage of lung volume receiving 10 Gy or more) were the top three in esophageal cancer. By comparing the differences in the threshold for parameters predicting RP between the two cancers, we saw that HAV30% retained the same value in both cancers. DVH parameters with HAV showed narrow differences in the threshold between the two cancer patient groups compared to conventional DVH parameters. DVH parameters with HAV may have higher commonality than conventional DVH parameters in both patient groups tested

Variation of Risk Factors for Cause-Specific Reintubation: A Preliminary Study

Unexpected reintubation may occur, even if the risk factors are considered and a spontaneous breathing trial is successful. Reintubation is thought to be caused by various factors. Several studies have investigated the risk factors of reintubation, but most did not classify reintubation by cause. We retrospectively classified patients undergoing reintubation at intensive care unit by cause (respiratory insufficiency vs. nonrespiratory insufficiency) to examine the cause-specific risk factors of reintubation. A total of 262 patients were included; reintubation within 48 hours after extubation was performed in 12 patients (reintubation rate, 4.5%). After classification by cause of reintubation, the pressure of arterial oxygen to fractional inspired oxygen concentration (P/F) ratio exhibited a significant association with reintubation only in the respiratory insufficiency group (odds ratio (OR) 0.989, 95% confidence interval (CI) 0.980 to 0.999, p=0.036, and OR 0.989, 95% CI 0.979 to 0.999, p=0.026, in the univariate and multivariate analyses, respectively). In the propensity score analysis, a P/F ratio ≤ 200 may be a risk factor for reintubation in the respiratory insufficiency group (OR 7.811, 95% CI 1.345 to 45.367, p=0.022). In the nonrespiratory insufficiency group, intubation duration was significantly related to reintubation (OR 1.165, 95% CI 1.012 to 1.342, p=0.033, and OR 1.163, 95% CI 1.004 to 1.348, p=0.044, in the univariate and multivariate analyses, respectively). In conclusion, a low P/F ratio at extubation may be a risk factor for reintubation due to respiratory insufficiency. In the nonrespiratory insufficiency group, intubation duration may be significantly related to reintubation. The risk factors for reintubation may differ by the cause of reintubation. Further large-scale randomized controlled trials are required