Preventive Care and Chronic Disease Management: Comparison of Appalachian and Non-Appalachian Community Health Centers in the United States

Introduction: The Appalachian region is often characterized by poor health outcomes and economic depression. Health centers (HCs) are community-based and patient-directed organizations that deliver comprehensive, culturally competent, high-quality primary healthcare services in high need areas, including Appalachia, where economic, geographic, or cultural factors can hinder access to healthcare services. Purpose: The study compares the clinical quality performance in preventive care and chronic disease management between Appalachian HCs and their non-Appalachian counterparts. Methods: Using 2015 Uniform Data System (UDS) health center data, bivariate and multivariate linear regression analyses examine the association of Appalachian HC with performance on preventive and chronic care clinical quality measures (CQMs). Results: In the multivariate analysis, patients served at Appalachian HCs are more likely to receive colorectal cancer screening and pediatric weight assessment and counseling than at non-Appalachian HCs. No statistically significant differences in performance observed among other CQMs. The percentage of Medicaid patients and total physician FTEs have positive associations with preventive care in colorectal and cervical cancer screening, pediatric weight assessment and counseling, and tobacco screening and cessation intervention as well as chronic disease management of aspirin therapy for ischemic vascular disease and hypertension control in the multivariate model. Implications: Overall Appalachian HCs perform as well as or better than non-Appalachian HCs in delivering preventive and chronic care services. Further examination of clinical quality improvement programs, insurance payer mix, and practice size among Appalachian HCs could advance the replication of clinical quality success for clinics in similar underserved communities

Nitric oxide regulates skeletal muscle fatigue, fiber type, microtubule organization, and mitochondrial ATP synthesis efficiency through cGMP-dependent mechanisms

Aim: Skeletal muscle nitric oxide–cyclic guanosine monophosphate (NO-cGMP) pathways are impaired in Duchenne and Becker muscular dystrophy partly because of reduced nNOSμ and soluble guanylate cyclase (GC) activity. However, GC function and the consequences of reduced GC activity in skeletal muscle are unknown. In this study, we explore the functions of GC and NO-cGMP signaling in skeletal muscle. Results: GC1, but not GC2, expression was higher in oxidative than glycolytic muscles. GC1 was found in a complex with nNOSμ and targeted to nNOS compartments at the Golgi complex and neuromuscular junction. Baseline GC activity and GC agonist responsiveness was reduced in the absence of nNOS. Structural analyses revealed aberrant microtubule directionality in GC1−/− muscle. Functional analyses of GC1−/− muscles revealed reduced fatigue resistance and postexercise force recovery that were not due to shifts in type IIA–IIX fiber balance. Force deficits in GC1−/− muscles were also not driven by defects in resting mitochondrial adenosine triphosphate (ATP) synthesis. However, increasing muscle cGMP with sildenafil decreased ATP synthesis efficiency and capacity, without impacting mitochondrial content or ultrastructure. Innovation: GC may represent a new target for alleviating muscle fatigue and that NO-cGMP signaling may play important roles in muscle structure, contractility, and bioenergetics. Conclusions: These findings suggest that GC activity is nNOS dependent and that muscle-specific control of GC expression and differential GC targeting may facilitate NO-cGMP signaling diversity. They suggest that nNOS regulates muscle fiber type, microtubule organization, fatigability, and postexercise force recovery partly through GC1 and suggest that NO-cGMP pathways may modulate mitochondrial ATP synthesis efficiency

Reduced Coupling of Oxidative Phosphorylation In Vivo Precedes Electron Transport Chain Defects Due to Mild Oxidative Stress in Mice

Oxidative stress and mitochondrial function are at the core of many degenerative conditions. However, the interaction between oxidative stress and in vivo mitochondrial function is unclear. We used both pharmacological (2 week paraquat (PQ) treatment of wild type mice) and transgenic (mice lacking Cu, Zn-superoxide dismutase (SOD1−/−)) models to test the effect of oxidative stress on in vivo mitochondrial function in skeletal muscle. Magnetic resonance and optical spectroscopy were used to measure mitochondrial ATP and oxygen fluxes and cell energetic state. In both models of oxidative stress, coupling of oxidative phosphorylation was significantly lower (lower P/O) at rest in vivo in skeletal muscle and was dose-dependent in the PQ model. Despite this reduction in efficiency, in vivo mitochondrial phosphorylation capacity (ATPmax) was maintained in both models, and ex vivo mitochondrial respiration in permeabilized muscle fibers was unchanged following PQ treatment. In association with the reduced P/O, PQ treatment led to a dose-dependent reduction in PCr/ATP ratio and increased phosphorylation of AMPK. These results indicate that oxidative stress uncouples oxidative phosphorylation in vivo and results in energetic stress in the absence of defects in the mitochondrial electron transport chain

Review-Development of Huckel Type Anions: From Molecular Modeling to Industrial Commercialization. A Success Story

This paper reviews the battery electrolyte technologies involving Huckel-type salts as a major electrolyte component. The concept was initially proposed by M. Armand in 1995 and then explored by several research groups. In the present review studies on the optimization of the electrolyte composition starting from molecular modeling through enhancing the yield of the salt synthesis to structural characterization and electrochemical performance are described. Furthermore, the use of the optimized electrolytes in a variety of lithium-ion and post-lithium batteries is presented and discussed. Finally, the commercialization of the up to date technology by Arkema is discussed as well as the performance of the present Huckel anion based electrolytes as compared to other marketed electrolyte technologies

Mean first-passage times of non-Markovian random walkers in confinement

The first-passage time (FPT), defined as the time a random walker takes to reach a target point in a confining domain, is a key quantity in the theory of stochastic processes. Its importance comes from its crucial role to quantify the efficiency of processes as varied as diffusion-limited reactions, target search processes or spreading of diseases. Most methods to determine the FPT properties in confined domains have been limited to Markovian (memoryless) processes. However, as soon as the random walker interacts with its environment, memory effects can not be neglected. Examples of non Markovian dynamics include single-file diffusion in narrow channels or the motion of a tracer particle either attached to a polymeric chain or diffusing in simple or complex fluids such as nematics \cite{turiv2013effect}, dense soft colloids or viscoelastic solution. Here, we introduce an analytical approach to calculate, in the limit of a large confining volume, the mean FPT of a Gaussian non-Markovian random walker to a target point. The non-Markovian features of the dynamics are encompassed by determining the statistical properties of the trajectory of the random walker in the future of the first-passage event, which are shown to govern the FPT kinetics.This analysis is applicable to a broad range of stochastic processes, possibly correlated at long-times. Our theoretical predictions are confirmed by numerical simulations for several examples of non-Markovian processes including the emblematic case of the Fractional Brownian Motion in one or higher dimensions. These results show, on the basis of Gaussian processes, the importance of memory effects in first-passage statistics of non-Markovian random walkers in confinement.Comment: Submitted version. Supplementary Information can be found on the Nature website : http://www.nature.com/nature/journal/v534/n7607/full/nature18272.htm

Modelling radiation-induced cell cycle delays

Ionizing radiation is known to delay the cell cycle progression. In particular after particle exposure significant delays have been observed and it has been shown that the extent of delay affects the expression of damage such as chromosome aberrations. Thus, to predict how cells respond to ionizing radiation and to derive reliable estimates of radiation risks, information about radiation-induced cell cycle perturbations is required. In the present study we describe and apply a method for retrieval of information about the time-course of all cell cycle phases from experimental data on the mitotic index only. We study the progression of mammalian cells through the cell cycle after exposure. The analysis reveals a prolonged block of damaged cells in the G2 phase. Furthermore, by performing an error analysis on simulated data valuable information for the design of experimental studies has been obtained. The analysis showed that the number of cells analyzed in an experimental sample should be at least 100 to obtain a relative error less than 20%.Comment: 19 pages, 11 figures, accepted for publication in Radiation and Environmental Biophysic

LRRK2 and RIPK2 variants in the NOD 2-mediated signaling pathway are associated with susceptibility to Mycobacterium leprae in Indian populations

In recent years, genome wide association studies have discovered a large number of gene loci that play a functional role in innate and adaptive immune pathways associated with leprosy susceptibility. The immunological control of intracellular bacteria M. leprae is modulated by NOD2-mediated signaling of Th1 responses. In this study, we investigated 211 clinically classified leprosy patients and 230 ethnically matched controls in Indian population by genotyping four variants in NOD2 (rs9302752A/G), LRRK2 (rs1873613A/G), RIPK2 (rs40457A/G and rs42490G/A). The LRRK2 locus is associated with leprosy outcome. The LRRK2 rs1873613A minor allele and respective rs1873613AA genotypes were significantly associated with an increased risk whereas the LRRK2 rs1873613G major allele and rs1873613GG genotypes confer protection in paucibacillary and leprosy patients. The reconstructed GA haplotypes from RIPK2 rs40457A/G and rs42490G/A variants was observed to contribute towards increased risk whereas haplotypes AA was observed to confer protective role. Our results indicate that a possible shared mechanisms underlying the development of these two clinical forms of the disease as hypothesized. Our findings confirm and validates the role of gene variants involved in NOD2-mediated signalling pathways that play a role in immunological control of intracellular bacteria M. leprae

Improved voltammetric methodology for chromium redox speciation in estuarine waters

Chromium is a toxic element naturally present in natural waters whose chemical speciation regulates its cycling, mobility and bioavailability. We present here: 1- an improved analytical method for chromium speciation (Cr(VI) vs Cr(III)) in estuarine samples by catalytic adsorptive cathodic stripping voltammetric (cat-AdCSV) and 2- a study highlighting a significant change of redox speciation during summer and winter. Initial measurements first revealed that surface-active substances (SAS) present in estuarine samples strongly influenced the analytical determination of Cr by partially masking the Cr peak through an increase of the background current. We found that the application of a low negative accumulation potential (−1.65 V) resulted in much better voltammograms compared to those obtained using the usual accumulation potential of −1.0 V. Using humic acid (HA) as a model SAS of natural origin, we show that this negative potential clearly prevents adsorption of SAS on the Hg-electrode surface, which in turns benefits the adsorption of the in-situ formed Cr(III)-DTPA complex and the resulting signal. The optimised method was applied to determine chromium redox speciation and distribution along the 23 km long salinity gradient, well oxygenated, Krka River estuary (Croatia). Cr(VI) was found to be the dominant redox species in both summer and winter, with Cr(III) contribution being lower in summer (up to ∼30%, average of ∼5%) than in winter (up to ∼50%, average of ∼30%). In summer, lower concentrations of Cr(VI) were found in the freshwater end-member (2.5 nM) than in the seawater end-member (4–5 nM), while the opposite trend was found in winter. Hexavalent chromium exhibited a non-conservative behaviour along the salinity gradient for both seasons. Chromium predominantly exists in dissolved phase, and contribution of particles reactive Cr(III) was minor