Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

https://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1006&context=covid19

SARS-CoV-2

A meta-analytic review of six types of nonpharmacological interventions, including dietary and psychological treatments, for children with ADHD found positive effects on ADHD symptoms for all types when raters were aware of treatment allocation (unblinded conditions). However, when raters were blinded, statistically significant effects on ADHD symptoms were found only for supplementation with omega-3/omega-6 free fatty acids or elimination of artificial food colorings, effects that were small or restricted to food-sensitive individuals.

https://ajp.psychiatryonline.org/doi/pdf/10.1176/appi.ajp.2012.12070991

Nonpharmacological Interventions for ADHD: Systematic Review and Meta-Analyses of Randomized Controlled Trials of Dietary and Psychological Treatments

Objective The increasing prevalence of obesity and type 2 diabetes (T2D) demonstrates the failure of conventional treatments to curb these diseases. The gut microbiota has been put forward as a key player in the pathophysiology of diet-induced T2D. Importantly, cranberry ( Vaccinium macrocarpon Aiton) is associated with a number of beneficial health effects. We aimed to investigate the metabolic impact of a cranberry extract (CE) on high fat/high sucrose (HFHS)-fed mice and to determine whether its consequent antidiabetic effects are related to modulations in the gut microbiota. Design C57BL/6J mice were fed either a chow or a HFHS diet. HFHS-fed mice were gavaged daily either with vehicle (water) or CE (200 mg/kg) for 8 weeks. The composition of the gut microbiota was assessed by analysing 16S rRNA gene sequences with 454 pyrosequencing. Results CE treatment was found to reduce HFHS-induced weight gain and visceral obesity. CE treatment also decreased liver weight and triglyceride accumulation in association with blunted hepatic oxidative stress and inflammation. CE administration improved insulin sensitivity, as revealed by improved insulin tolerance, lower homeostasis model assessment of insulin resistance and decreased glucose-induced hyperinsulinaemia during an oral glucose tolerance test. CE treatment was found to lower intestinal triglyceride content and to alleviate intestinal inflammation and oxidative stress. Interestingly, CE treatment markedly increased the proportion of the mucin-degrading bacterium Akkermansia in our metagenomic samples. Conclusions CE exerts beneficial metabolic effects through improving HFHS diet-induced features of the metabolic syndrome, which is associated with a proportional increase in Akkermansia spp. population.

https://gut.bmj.com/content/gutjnl/64/6/872.full.pdf

A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice

The mammalian mitochondrial electron transport chain (ETC) includes complexes I‑IV, as well as the electron transporters ubiquinone and cytochrome c. There are two electron transport pathways in the ETC: Complex I/III/IV, with NADH as the substrate and complex II/III/IV, with succinic acid as the substrate. The electron flow is coupled with the generation of a proton gradient across the inner membrane and the energy accumulated in the proton gradient is used by complex V (ATP synthase) to produce ATP. The first part of this review briefly introduces the structure and function of complexes I‑IV and ATP synthase, including the specific electron transfer process in each complex. Some electrons are directly transferred to O2 to generate reactive oxygen species (ROS) in the ETC. The second part of this review discusses the sites of ROS generation in each ETC complex, including sites IF and IQ in complex I, site IIF in complex II and site IIIQo in complex III, and the physiological and pathological regulation of ROS. As signaling molecules, ROS play an important role in cell proliferation, hypoxia adaptation and cell fate determination, but excessive ROS can cause irreversible cell damage and even cell death. The occurrence and development of a number of diseases are closely related to ROS overproduction. Finally, proton leak and uncoupling proteins (UCPS) are discussed. Proton leak consists of basal proton leak and induced proton leak. Induced proton leak is precisely regulated and induced by UCPs. A total of five UCPs (UCP1‑5) have been identified in mammalian cells. UCP1 mainly plays a role in the maintenance of body temperature in a cold environment through non‑shivering thermogenesis. The core role of UCP2‑5 is to reduce oxidative stress under certain conditions, therefore exerting cytoprotective effects. All diseases involving oxidative stress are associated with UCPs.

/pdf/mitochondrial-electron-transport-chain-ros-generation-and-1ba3ps939u.pdf

Mitochondrial electron transport chain, ROS generation and uncoupling (Review)

Significance: Nonalcoholic fatty liver disease (NAFLD), characterized by liver triacylglycerol build-up, has been growing in the global world in concert with the raised prevalence of cardiometabolic disorders, including obesity, diabetes, and hyperlipemia. Redox imbalance has been suggested to be highly relevant to NAFLD pathogenesis. Recent Advances: As a major health problem, NAFLD progresses to the more severe nonalcoholic steatohepatitis (NASH) condition and predisposes susceptible individuals to liver and cardiovascular disease. Although NAFLD represents the predominant cause of chronic liver disorders, the mechanisms of its development and progression remain incompletely understood, even if various scientific groups ascribed them to the occurrence of insulin resistance, dyslipidemia, inflammation, and apoptosis. Nevertheless, oxidative stress (OxS) more and more appears as the most important pathological event during NAFLD development and the hallmark between simple steatosis and NASH manif...

Oxidative Stress as a Critical Factor in Nonalcoholic Fatty Liver Disease Pathogenesis

Purpose of reviewVarious studies have delineated the causal role of dietary cholesterol in atherogenesis Strategies have thus been developed to minimize cholesterol absorption, and cholesterol transport proteins found at the apical membrane of enterocytes have been extensively investigated This re

Intestinal cholesterol transport proteins: an update and beyond.

PCSK9 plays a significant role in cholesterol homeostasis and lipid transport in intestinal epithelial cells

Significance: Lactoferrin (Lf) is a nonheme iron-binding glycoprotein strongly expressed in human and bovine milk and it plays many functions during infancy such as iron homeostasis and defense against microorganisms. In humans, Lf is mainly expressed in mucosal epithelial and immune cells. Growing evidence suggests multiple physiological roles for Lf after weaning. Recent Advances: The aim of this review is to highlight the recent advances concerning multifunctional Lf activities. Critical Issues: First, we will provide an overview of the mechanisms related to Lf intrinsic synthesis or intestinal absorption as well as its interaction with a wide spectrum of mammalian receptors and distribution in organs and cell types. Second, we will discuss the large variety of its physiological functions such as iron homeostasis, transportation, immune regulation, oxidative stress, inflammation, and apoptosis while specifying the mechanisms of action. Third, we will focus on its recent physiopathology implica...

Lactoferrin, a Pleiotropic Protein in Health and Disease

Significance: Metabolic syndrome (MetS) is associated with a greater risk of diabetes and cardiovascular diseases. It is estimated that this multifactorial condition affects 20%–30% of the world's population. A detailed understanding of MetS mechanisms is crucial for the development of effective prevention strategies and adequate intervention tools that could curb its increasing prevalence and limit its comorbidities, particularly in younger age groups. With advances in basic redox biology, oxidative stress (OxS) involvement in the complex pathophysiology of MetS has become widely accepted. Nevertheless, its clear association with and causative effects on MetS require further elucidation. Recent Advances: Although a better understanding of the causes, risks, and effects of MetS is essential, studies suggest that oxidant/antioxidant imbalance is a key contributor to this condition. OxS is now understood to be a major underlying mechanism for mitochondrial dysfunction, ectopic lipid accumulation, a...

Schohraya Spahis

Papers

Oxidative Stress as a Critical Factor in Nonalcoholic Fatty Liver Disease Pathogenesis

Intestinal cholesterol transport proteins: an update and beyond.

PCSK9 plays a significant role in cholesterol homeostasis and lipid transport in intestinal epithelial cells

Lactoferrin, a Pleiotropic Protein in Health and Disease

Metabolic Syndrome as a Multifaceted Risk Factor for Oxidative Stress