Consequences of Hyperoxia and the Toxicity of Oxygen in the Lung

Oxygen (O2) is life essential but as a drug has a maximum positive biological benefit and accompanying toxicity effects. Oxygen is therapeutic for treatment of hypoxemia and hypoxia associated with many pathological processes. Pathophysiological processes are associated with increased levels of hyperoxia-induced reactive O2 species (ROS) which may readily react with surrounding biological tissues, damaging lipids, proteins, and nucleic acids. Protective antioxidant defenses can become overwhelmed with ROS leading to oxidative stress. Activated alveolar capillary endothelium is characterized by increased adhesiveness causing accumulation of cell populations such as neutrophils, which are a source of ROS. Increased levels of ROS cause hyperpermeability, coagulopathy, and collagen deposition as well as other irreversible changes occurring within the alveolar space. In hyperoxia, multiple signaling pathways determine the pulmonary cellular response: apoptosis, necrosis, or repair. Understanding the effects of O2 administration is important to prevent inadvertent alveolar damage caused by hyperoxia in patients requiring supplemental oxygenation

Integrated system for traction and battery charging of electric vehicles with universal interface to the power grid

This paper proposes an integrated system for traction and battery charging of electric vehicles (EVs) with universal interface to the power grid. In the proposed system, the power electronics converters comprising the traction drive system are also used for the battery charging system, reducing the required hardware, meaning the integrated characteristic of the system. Besides, this interface is universal, since it can be performed with the three main types of power grids, namely: (1) Single-phase AC power grids; (2) Three-phase AC power grids; (3) DC power grids. In these three types of interfaces with the power grid, as well as in the traction drive operation mode, bidirectional operation is possible, framing the integration of this system into an EV in the context of smart grids. Moreover, the proposed system endows an EV with an on-board fast battery charger, whose operation allows either fast or slow battery charging. The main contributes of the proposed system are detailed in the paper, and simulation results are presented in order to attain the feasibility of the proposed system.This work has been supported by COMPETE: POCI-01-0145-FEDER-007043 and FCT -Fundacao para a Ciencia e Tecnologia within the Project Scope: UID/CEC/00319/2013. This work has been supported by FCT within the Project Scope DAIPESEV - Development of Advanced Integrated Power Electronic Systems for Electric Vehicles: PTDC/EEI-EEE/30382/2017. Mr. Tiago Sousa is supported by the doctoral scholarship SFRH/BD/134353/2017 granted by the Portuguese FCT agency. This work is part of the FCT project 0302836 NORTE-01-0145-FEDER-030283

Study protocol, randomized controlled trial: reducing symptom burden in patients with heart failure with preserved ejection fraction using ubiquinol and/or D-ribose

Abstract Background Heart failure (HF), the leading cause of morbidity and mortality in the US, affects 6.6 million adults with an estimated additional 3 million people by 2030. More than 50% of HF patients have heart failure with preserved left ventricular ejection fraction (HFpEF). These patients have impaired cardiac muscle relaxation and diastolic filling, which investigators have associated with cellular energetic impairment. Patients with HFpEF experience symptoms of: (1) fatigue; (2) shortness of breath; and (3) swelling (edema) of the lower extremities. However, current HF guidelines offer no effective treatment to address these underlying pathophysiologic mechanisms. Thus, we propose a biobehavioral symptom science study using ubiquinol and D-ribose (therapeutic interventions) to target mitochondrial bioenergetics to reduce the complex symptoms experienced by patients with HFpEF. Methods Using a randomized, double-blind, placebo-controlled design, the overall objective is to determine if administering ubiquinol and/or D-ribose to HFpEF patients for 12 weeks would decrease the severity of their complex symptoms and improve their cardiac function. The measures used to assess patients’ perceptions of their health status and level of vigor (energy) will be the Kansas City Cardiomyopathy Questionnaire (KCCQ) and Vigor subscale of the Profile of Mood States. The 6-min walk test will be used to test exercise tolerance. Left ventricular diastolic function will be assessed using innovative advanced echocardiography software called speckle tracking. We will measure B-type natriuretic peptides (secreted from ventricles in HF) and lactate/ATP ratio (measure of cellular energetics). Discussions Ubiquinol (active form of Coenzyme Q10) and D-ribose are two potential treatments that can positively affect cellular energetic impairment, the major underlying mechanism of HFpEF. Ubiquinol, the reduced form of CoQ10, is more effective in adults over the age of 50. In patients with HFpEF, mitochondrial deficiency of ubiquinol results in decreased adenosine triphosphate (ATP) synthesis and reduced scavenging of reactive oxygen species. D-ribose is a substrate required for ATP synthesis and when administered has been shown to improve impaired myocardial bioenergetics. Therefore, if the biological underpinning of deficient mitochondrial ATP in HFpEF is not addressed, patients will suffer major symptoms including lack of energy, fatigue, exertional dyspnea, and exercise intolerance. Trial registration ClinicalTrials.gov Identifier: NCT03133793; Data of Registration: April 28, 2017

Brief of \u3ci\u3eAmici Curiae\u3c/i\u3e Law Professors and Economists in Support of Petitioner in \u3ci\u3eSouth Dakota v. Wayfair, Inc., et al.\u3c/i\u3e

Amici are professors of tax law and economics at universities across the United States. As scholars and teachers, they have considered the economic consequences of this Court’s decision in Quill Corp. v. North Dakota, 504 U.S. 298 (1992), and have concluded that Quill’s dormant Commerce Clause holding should be overruled. Amici join this brief solely on their own behalf and not as representatives of their universities. A full list of amici appears in Appendix A