Beneficial effects of acute inhibition of the oxidative pentose phosphate pathway in the failing heart.

In vitro studies suggested that glucose metabolism through the oxidative pentose phosphate pathway (oxPPP) can paradoxically feed superoxide-generating enzymes in failing hearts. We therefore tested the hypothesis that acute inhibition of the oxPPP reduces oxidative stress and enhances function and metabolism of the failing heart, in vivo. In 10 chronically instrumented dogs, congestive heart failure (HF) was induced by high-frequency cardiac pacing. Myocardial glucose consumption was enhanced by raising arterial glycemia to levels mimicking post-prandial peaks, before and after intravenous administration of the oxPPP inhibitor 6-aminonicotinamide (80 mg/kg). Myocardial energy substrate metabolism was measured with radiolabeled glucose and oleic acid, and cardiac 8-isoprostane output was used as an index of oxidative stress. A group of 5 chronically instrumented, normal dogs served as control. In HF, raising glycemic levels from ~80 to ~170 mg/dL increased cardiac isoprostane output by approximately 2-fold, while oxPPP inhibition normalized oxidative stress and enhanced cardiac oxygen consumption, glucose oxidation and stroke work. In normal hearts glucose infusion did not induce significant changes in cardiac oxidative stress. Myocardial tissue concentration of 6P-gluconate, an intermediate metabolite of the oxPPP, was significantly reduced by approximately 50% in treated vs non-treated failing hearts, supporting the inhibitory effect of 6-aminonicotinamide. Our study indicates an important contribution of the oxPPP activity to cardiac oxidative stress in HF, which is particularly pronounced during common physiological changes such as post-prandial glycemic peaks

Prevalence of depression and its impact on quality of life in frontline otorhinolaryngology nurses during the COVID-19 pandemic in China

Objective: Exposure to the coronavirus disease 2019 (COVID-19) was associated with high risk of mental health problems among frontline nurses. This study examined the prevalence of depressive symptoms (depression hereafter) and its impact on quality of life (QOL) in otorhinolaryngology (ENT) nurses during the COVID-19 pandemic in China. Methods: An online study was conducted between March 15 and March 20, 2020. Depression and QOL were assessed using standardized instruments. Results: A total of 1,757 participants were recruited. The prevalence of depression was 33.75% (95% CI: 31.59%-35.97%). Results emerging from multiple logistic regression analysis showed that direct care of COVID-19 patients (OR: 1.441, 95% CI: 1.031– 2.013, P = 0.032), and current smoking (OR: 2.880, 95% CI: 1.018–8.979, P = 0.048) were significantly associated with depression. After controlling for covariates, ENT nurses with depression had a lower overall QOL compared to those without depression (F(1, 1757) = 536.80, P \u3c 0.001). Conclusions: Depression was common among ENT nurses during the COVID-19 pandemic in China. Considering the negative impact of depression on QOL and care quality, regular screening for depression should be conducted in ENT nurses and treatment should be provided

Prevalence and correlates of fatigue and its association with quality of life among clinically stable older psychiatric patients during the COVID-19 outbreak: A cross-sectional study

Background: The pattern of fatigue in older psychiatric patients during the COVID-19 outbreak was unknown. This study examined the prevalence of fatigue and its association with overall quality of life (overall QOL) in clinically stable older patients with psychiatric disorders during the COVID-19 outbreak. Methods: This was a multicenter, cross-sectional study. Fatigue, depressive symptoms, pain, insomnia symptoms, and overall QOL were assessed with standardized instruments. Results: A total of 1063 patients were recruited. The prevalence of fatigue was 47.1% (95%CI: 44.1–50.1%). An analysis of covariance revealed that overall QOL was significantly lower in patients with fatigue compared to those without (P = 0.011). A multiple logistic regression analysis revealed that more severe depressive symptoms (OR = 1.15, P \u3c 0.001), insomnia symptoms (OR = 1.08, P \u3c 0.001) and pain (OR = 1.43, P \u3c 0.001) were significantly associated with fatigue. Conclusions: Fatigue is common among clinically stable older patients with psychiatric disorders during the COVID-19 outbreak. Considering its negative impact on overall QOL, regular assessment of fatigue and appropriate treatment warrant attention in this subpopulation

Identification of Hsc70 as target for AGE modification in senescent human fibroblasts

Cellular senescence is known as a potent mechanism of tumor suppression, and cellular senescence in vitro also reflects at least some features of aging in vivo. The Free Radical Theory of aging suggests that reactive oxygen species are important causative agents of aging and cellular senescence. Besides damage of nucleic acids and lipids, also oxidative modifications of proteins have been described as potential causative events in the senescence response. However, the identity of protein targets for post-translational modifications in senescent cells has remained unclear. In the present communication, we analyzed the occurrence of oxidative posttranslational modifications in senescent human endothelial cells and dermal fibroblasts. We found a significant increase in the level of protein carbonyls and AGE modification with senescence in both cell types. Using 2D-Gel electrophoresis and Western Blot we found that heat shock cognate protein 70 is a bona fide target for AGE modification in human fibroblasts