Obstructive Sleep Apnoea Syndrome, Endothelial Function and Markers of Endothelialization. Changes after CPAP

STUDY OBJECTIVES: This study tries to assess the endothelial function in vivo using flow-mediated dilatation (FMD) and several biomarkers of endothelium formation/restoration and damage in patients with obstructive sleep apnoea (OSA) syndrome at baseline and after three months with CPAP therapy. DESIGN: Observational study, before and after CPAP therapy. SETTING AND PATIENTS: We studied 30 patients with apnoea/hypopnoea index (AHI) >15/h that were compared with themselves after three months of CPAP therapy. FMD was assessed non-invasively in vivo using the Laser-Doppler flowmetry. Circulating cell-free DNA (cf-DNA) and microparticles (MPs) were measured as markers of endothelial damage and the vascular endothelial growth factor (VEGF) was determined as a marker of endothelial restoration process. MEASUREMENTS AND RESULTS: After three month with CPAP, FMD significantly increased (1072.26 ± 483.21 vs. 1604.38 ± 915.69 PU, p< 0.005) cf-DNA and MPs significantly decreased (187.93 ± 115.81 vs. 121.28 ± 78.98 pg/ml, p<0.01, and 69.60 ± 62.60 vs. 39.82 ± 22.14 U/μL, p<0.05, respectively) and VEGF levels increased (585.02 ± 246.06 vs. 641.11 ± 212.69 pg/ml, p<0.05). These changes were higher in patients with more severe disease. There was a relationship between markers of damage (r = -0.53, p<0.005) but not between markers of damage and restoration, thus suggesting that both types of markers should be measured together. CONCLUSIONS: CPAP therapy improves FMD. This improvement may be related to an increase of endothelial restoration process and a decrease of endothelial damage

Chemical physics insight of PPy-based modified ion exchange membranes: a fundamental approach

Four commercially available, cost-effective ion exchange membranes (two cationic and two anionic exchange membranes, CEMs and AEMs, respectively) were modified to mitigate crossover phenomena of the redox active species typically observed in Aqueous Organic Redox Flow Batteries (AORFB) systems. The modification strategy was carried out using a pyrrole(Py)-based polymer which successfully reduced the permeation of two redox active organic molecules, a viologen derivative (named BP7 throughout this study) and TEMPOL, by an order of magnitude. Additionally, modified membranes showed not significant changes in ion conductivity, with negligible effect on the electrical conductivity of the membranes at a given conditions. The morphology, physicochemical, mechanical, and electrochemical properties of the membranes were determined to evaluate the impact of these modifications. AEMs modified in this manner were found to have optimal properties, showing an increase in ion exchange capacity while maintaining excellent mechanical stability and unaltered permselectivity. Additionally, the diffusion boundary layer of these AEMs was slightly extended, which suggests a greater double layer stability for ion exchange processes than in the case of CEMs. Our work shows that these modified membranes could be an appealing approach for AORFB applicationsThis work has been funded by the European Union under the HIGREEW project, Affordable High-performance Green Redox Flow batteries (Grant agreement no. 875613). H2020: LC-BAT-4-2019875613

Roadmap to the multidisciplinary design analysis and optimisation of wind energy systems

A research agenda is described to further encourage the application of Multidisciplinary Design Analysis and Optimisation (MDAO) methodologies to wind energy systems. As a group of researchers closely collaborating within the International Energy Agency (IEA) Wind Task 37 for Wind Energy Systems Engineering: Integrated Research, Design and Development, we have identified challenges that will be encountered by users building an MDAO framework. This roadmap comprises 17 research questions and activities recognised to belong to three research directions: model fidelity, system scope and workflow architecture. It is foreseen that sensible answers to all these questions will enable to more easily apply MDAO in the wind energy domain. Beyond the agenda, this work also promotes the use of systems engineering to design, analyse and optimise wind turbines and wind farms, to complement existing compartmentalised research and design paradigms

SC83288 is a clinical development candidate for the treatment of severe malaria

Severe malaria is a life-threatening complication of an infection with the protozoan parasite Plasmodium falciparum, which requires immediate treatment. Safety and efficacy concerns with currently used drugs accentuate the need for new chemotherapeutic options against severe malaria. Here we describe a medicinal chemistry program starting from amicarbalide that led to two compounds with optimized pharmacological and antiparasitic properties. SC81458 and the clinical development candidate, SC83288, are fast-acting compounds that can cure a P. falciparum infection in a humanized NOD/SCID mouse model system. Detailed preclinical pharmacokinetic and toxicological studies reveal no observable drawbacks. Ultra-deep sequencing of resistant parasites identifies the sarco/endoplasmic reticulum Ca(2+) transporting PfATP6 as a putative determinant of resistance to SC81458 and SC83288. Features, such as fast parasite killing, good safety margin, a potentially novel mode of action and a distinct chemotype support the clinical development of SC83288, as an intravenous application for the treatment of severe malaria

Transcriptome analysis in blood cells from children reveals potential early biomarkers of metabolic alterations

OBJECTIVES: The development of effective strategies to prevent childhood obesity and its comorbidities requires new, reliable early biomarkers. Here, we aimed to identify in peripheral blood cells potential transcript-based biomarkers of unhealthy metabolic profile associated to overweight/obesity in children. METHODS: We performed a whole-genome microarray analysis in blood cells to identify genes differentially expressed between overweight and normal weight children to obtain novel transcript-based biomarkers predictive of metabolic complications. RESULTS: The most significant enriched pathway of differentially expressed genes was related to oxidative phosphorylation, for which most of genes were downregulated in overweight versus normal weight children. Other genes were involved in carbohydrate metabolism/glucose homoeostasis or in lipid metabolism (for example, TCF7L2, ADRB3, LIPE, GIPR), revealing plausible mechanisms according to existing biological knowledge. A set of differentially expressed genes was identified to discriminate in overweight children those with high or low triglyceride levels. CONCLUSIONS: Functional microarray analysis has revealed a set of potential blood-cell transcript-based biomarkers that may be a useful approach for early identification of children with higher predisposition to obesity-related metabolic alterations

Gap-anisotropic model for the narrow-gap Kondo insulators

A theory is presented which accounts for the dynamical generation of a hybridization gap with nodes in the Kondo insulating materials $CeNiSn$ and $CeRhSb$. We show that Hunds interactions acting on virtual $4f^2$ configurations of the cerium ion can act to dynamically select the shape of the cerium ion by generating a Weiss field which couples to the shape of the ion. In low symmetry crystals where the external crystal fields are negligible, this process selects a nodal Kondo semimetal state as the lowest energy configuration.Comment: Substantially Revised Versio

Energy loss of protons and deuterons at low energies in Pd polycrystalline thin films

We have investigated experimentally and by computer simulations the energy loss  distributions of low energy (E <10 keV) protons and deuterons transmitted through  polycrystalline palladium thin flms. In contrast with previous experiments on various transition metals we find that the stopping power of Pd is proportional to the ion velocity. Data of protons and deuterons are coincident within the experimental uncertainties, showing the absence of an isotopic effect on the stopping power of Pd in this energy range. The experimental results were analyzed and compared with Monte Carlo computer simulations and previous theoretical models. The dference in the velocity dependence of the energy loss of hydrogen ions in Pd with respect to other transition metals (Cu, Ag and Au) is explained by a theoretical analysis based on the properties of the d-electron bands of those elements.Fil: Celedón, C.. Comisión Nacional de Energía Atómica. Gerencia del Area de Energía Nuclear. Instituto Balseiro; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Area de Investigación y Aplicaciones No Nucleares. Gerencia de Física (Centro Atómico Bariloche); ArgentinaFil: Sanchez, Esteban Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Area de Investigación y Aplicaciones No Nucleares. Gerencia de Física (Centro Atómico Bariloche); Argentina. Comisión Nacional de Energía Atómica. Gerencia del Area de Energía Nuclear. Instituto Balseiro; ArgentinaFil: Moreno, Mario Sergio Jesus. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Area de Investigación y Aplicaciones No Nucleares. Gerencia de Física (Centro Atómico Bariloche); Argentina. Comisión Nacional de Energía Atómica. Gerencia del Area de Energía Nuclear. Instituto Balseiro; ArgentinaFil: Arista, Nestor Ricardo. Comisión Nacional de Energía Atómica. Gerencia del Area de Investigación y Aplicaciones No Nucleares. Gerencia de Física (Centro Atómico Bariloche); Argentina. Comisión Nacional de Energía Atómica. Gerencia del Area de Energía Nuclear. Instituto Balseiro; ArgentinaFil: Uribe, J. D.. Universidad Técnica Federico Santa María. Departamento de Física. Laboratorio de Colisiones Atómicas; ChileFil: Mery, M.. Universidad Técnica Federico Santa María. Departamento de Física. Laboratorio de Colisiones Atómicas; ChileFil: Valdés, J. E.. Universidad Técnica Federico Santa María. Departamento de Física. Laboratorio de Colisiones Atómicas; ChileFil: Vargas, P.. Universidad Técnica Federico Santa María. Departamento de Física. Laboratorio de Colisiones Atómicas; Chil