Low aerobic capacity in McArdle disease : A role for mitochondrial network impairment?

McArdle disease is caused by myophosphorylase deficiency and results in complete inability for muscle glycogen breakdown. A hallmark of this condition is muscle oxidation impairment (e.g., low peak oxygen uptake (VO)), a phenomenon traditionally attributed to reduced glycolytic flux and Krebs cycle anaplerosis. Here we hypothesized an additional role for muscle mitochondrial network alterations associated with massive intracellular glycogen accumulation. We analyzed in depth mitochondrial characteristics-content, biogenesis, ultrastructure-and network integrity in skeletal-muscle from McArdle/control mice and two patients. We also determined VO in patients (both sexes, N = 145) and healthy controls (N = 133). Besides corroborating very poor VO values in patients and impairment in muscle glycolytic flux, we found that, in McArdle muscle: (a) damaged fibers are likely those with a higher mitochondrial and glycogen content, which show major disruption of the three main cytoskeleton components-actin microfilaments, microtubules and intermediate filaments-thereby contributing to mitochondrial network disruption in skeletal muscle fibers; (b) there was an altered subcellular localization of mitochondrial fission/fusion proteins and of the sarcoplasmic reticulum protein calsequestrin-with subsequent alteration in mitochondrial dynamics/function; impairment in mitochondrial content/biogenesis; and (c) several OXPHOS-related complex proteins/activities were also affected. In McArdle disease, severe muscle oxidative capacity impairment could also be explained by a disruption of the mitochondrial network, at least in those fibers with a higher capacity for glycogen accumulation. Our findings might pave the way for future research addressing the potential involvement of mitochondrial network alterations in the pathophysiology of other glycogenoses

Whole genome sequencing of Shigella sonnei through PulseNet Latin America and Caribbean: advancing global surveillance of foodborne illnesses

Objectives Shigella sonnei is a globally important diarrhoeal pathogen tracked through the surveillance network PulseNet Latin America and Caribbean (PNLA&C), which participates in PulseNet International. PNLA&C laboratories use common molecular techniques to track pathogens causing foodborne illness. We aimed to demonstrate the possibility and advantages of transitioning to whole genome sequencing (WGS) for surveillance within existing networks across a continent where S. sonnei is endemic. Methods We applied WGS to representative archive isolates of S. sonnei (n = 323) from laboratories in nine PNLA&C countries to generate a regional phylogenomic reference for S. sonnei and put this in the global context. We used this reference to contextualise 16 S. sonnei from three Argentinian outbreaks, using locally generated sequence data. Assembled genome sequences were used to predict antimicrobial resistance (AMR) phenotypes and identify AMR determinants. Results S. sonnei isolates clustered in five Latin American sublineages in the global phylogeny, with many (46%, 149 of 323) belonging to previously undescribed sublineages. Predicted multidrug resistance was common (77%, 249 of 323), and clinically relevant differences in AMR were found among sublineages. The regional overview showed that Argentinian outbreak isolates belonged to distinct sublineages and had different epidemiologic origins. Conclusions Latin America contains novel genetic diversity of S. sonnei that is relevant on a global scale and commonly exhibits multidrug resistance. Retrospective passive surveillance with WGS has utility for informing treatment, identifying regionally epidemic sublineages and providing a framework for interpretation of prospective, locally sequenced outbreaks

Statistical shape modeling of the hip and the association with hip osteoarthritis: a systematic review

Objective: To summarize available evidence on the association between hip shape as quantified by statistical shape modeling (SSM) and the incidence or progression of hip osteoarthritis. Design: We conducted a systematic search of five electronic databases, based on a registered protocol (available: PROSPERO CRD42020145411). Articles presenting original data on the longitudinal relationship between radiographic hip shape (quantified by SSM) and hip OA were eligible. Quantitative meta-analysis was precluded because of the use of different SSM models across studies. We used the Newcastle–Ottawa Scale (NOS) for risk of bias assessment. Results: Nine studies (6,483 hips analyzed with SSM) were included in this review. The SSM models used to describe hip shape ranged from 16 points on the femoral head to 85 points on the proximal femur and hemipelvis. Multiple hip shape features and combinations thereof were associated with incident or progressive hip OA. Shape variants that seemed to be consistently associated with hip OA across studies were acetabular dysplasia, cam morphology, and deviations in acetabular version (either excessive anteversion or retroversion). Conclusions: Various radiographic, SSM-defined hip shape features are associated with hip OA. Some hip shape features only seem to increase the risk for hip OA when combined together. The heterogeneity of the used SSM models across studies precludes the estimation of pooled effect sizes. Further studies using the same SSM model and definition of hip OA are needed to allow for the comparison of outcomes across studies, and to validate the found associations

Fluoride dynamics in the granitic aquifer of the Wailapally watershed, Nalgonda District, India

High concentrations of fluoride (up to 7.6 mg/L) are a recognized feature of the Wailapally granitic aquifer of Nalgonda District, Andhra Pradesh, India. The basement rocks provide abundant sources of F in the form of amphibole, biotite, fluorite and apatite. The whole-rock concentrations of F in the aquifer are in the range 240–990 mg/kg. Calcretes from the shallow weathered horizons also contain comparably high concentrations of F (635–950 mg/kg). The concentrations of water-soluble F in the granitic rocks and the calcretes are usually low (1% of the total or less) but broadly correlate with the concentrations observed in groundwaters in the local vicinity. The water-soluble fraction of fluoride is relatively high in weathered calcretes compared to fresh calcretes. Groundwater major-ion composition shows a well-defined trend with flow downgradient in the Wailapally aquifer, from Na–Ca–HCO3-dominated waters in the recharge area at the upper part of the catchment, through to Na–Mg–HCO3 and ultimately to Na–HCO3 and Na–HCO3–Cl types in the discharge area in the lowest part. The evolution occurs over a reach spanning some 17 km. Groundwater chemistry evolves by silicate weathering reactions, although groundwaters rapidly reach equilibrium with carbonate minerals, favouring precipitation of calcite, and ultimately dolomite in the lower parts of the watershed. This precipitation is also aided by evapotranspiration. Decreasing Ca activity downgradient leads to a dominance of fluorite-undersaturated conditions and consequently to mobilisation of F. Despite the clear downgradient evolution of major-ion chemistry, concentrations of F remain relatively uniform in the fluorite-undersaturated groundwaters, most being in the range 3.0–7.6 mg/L. The rather narrow range is attributed to a mechanism of co-precipitation with and/or adsorption to calcrete in the lower sections of the aquifer. The model may find application in other high-F groundwaters from granitic aquifers of semi-arid regions

Acute Responses to On-Court Repeated-Sprint Training Performed With Blood Flow Restriction Versus Systemic Hypoxia in Elite Badminton Athletes.

Repeated-sprint training (RS) is commonly conducted in normoxia, but its completion with localized (blood-flow restriction [BFR]) or systemic hypoxia has been proven effective for performance enhancement. Yet, few studies have applied these types of RS sessions in racket sports. The authors aimed to determine the acute responses to these types of training in elite badminton players. Eight male elite badminton players participated in this randomized crossover study. They performed 3 on-court RS sessions, each consisting of 3 sets of 10 repetitions of 10-s badminton-specific movements in normoxia (RSN), systemic normobaric hypoxia (RSH, FiO2 = 14%), or with BFR (RS-BFR, 40% arterial occlusion pressure). Performance, perceptual (ie, rating of perceived exertion), and physiological (ie, pulse saturation, muscle oxygenation, blood lactate, creatine kinase, heart-rate variability) responses were measured after each set and up to 48 h postsession. RS-BFR induced a greater performance impairment (lower distance and accelerations) and a higher local perceived exertion in the legs than RSN and RSH (P < .05), whereas greater overall fatigue was reported with RSH (P < .05). RSH induced a lower saturation (P < .001), but no differences were observed in muscle oxygenation between conditions. No differences in creatine kinase or heart-rate variability were observed at any time point (from baseline up to 48 h after the session). RS-BFR-and, to a lower extent, RSH-resulted in impaired performance and a higher perceived strain than RSN. However, these 2 hypoxic methods do not seem to induce a long-lasting (post 24-48 h) physiological stress in elite badminton players

Factores socioeducativos asociados a la percepción de maltrato en estudiantes de medicina peruanos

Introducción: muchas veces para mejorar el aprendizaje los docentes realizan algún tipo de maltrato, lo que provoca gran frecuencia de este en estudiantes de medicina. Sin embargo, no se han explorado sus determinantes en una población estudiantil extensa. Objetivo: determinar los factores socioeducativos que se asociaron a la percepción del maltrato entre los estudiantes de medicina peruanos. Métodos: estudio transversal analítico, multicéntrico en más de 1 000 estudiantes en todo el Perú. Se usó una encuesta validada para maltrato estudiantil, buscando asociación a variables socioeducativas. Se realizó un muestreo por bola de nieves, se halló asociaciones estadísticas usando modelos lineales generalizados. Resultados: las mujeres sufrían menos maltrato físico (razón de prevalencias ajustadas (RPa): 0,86), pero más sexual (RPa: 1,54). Los de universidades privadas tenían menor maltrato físico (RPa: 0,80), los homosexuales tuvieron mayor maltrato psicológico, académico y sexual (RPa: 1,81; 1,78 y 2,07; respectivamente), los bisexuales mayor maltrato sexual (RPa: 1,50), los que tenían sobrepeso/obesidad mayor maltrato psicológico (RPa: 1,21), a más años en los hospitales se tuvo mayor maltrato psicológico y sexual (RPa: 1,10 y 1,09; respectivamente), los que hacían guardias extras y eran internos de medicina tuvieron mayores maltratos físicos (RPa: 1,22 y 1,40; respectivamente) y académicos (RPa: 1,21 y 1,46; respectivamente), los satisfechos con la carrera tenían menor frecuencia de los cuatro tipos de maltrato. Conclusiones: se encontró que algunos estudiantes eran más maltratados, se deben tomar las medidas para que esto se caracterice, intervenga y reduzca, ya que podría tener consecuencias en el estudiante, su rendimiento y que repercutan hasta cuando este sea profesional

Investigación socio-ecológica a largo plazo en la Patagonia Austral: Estrategias interdisciplinarias para lograr la conservación de los recursos naturales a través de un manejo sustentable bajo escenarios de cambio global

Las dimensiones ecológicas, sociales, institucionales y políticas de los problemas ambientales abarcan escalas espaciales y temporales que exceden a la mayoría de las investigaciones científicas. Una alternativa que crece con el tiempo a nivel mundial es la aproximación Long-Term Ecological Research (LTER) o Long-Term Socio-Ecological Research (LTSER), pero que presenta vacíos temáticos y geográficos. Uno de estos vacíos es la Argentina, sin embargo, existe una gran cantidad de experiencia para poder integrar potencialmente al país a dicha red. El objetivo de este trabajo es evaluar el marco general de la investigación ecológica a largo plazo que se realiza en Argentina, y particularmente en la Patagonia Austral, tomamos dos líneas de trabajo como estudios de caso: (i) la ecología y conservación de los bosques nativos a través del manejo forestal y silvopastoril sostenible, y (ii) la ecología y el manejo de las invasiones biológicas. Se presenta una reseña de las investigaciones realizadas (en el pasado y al presente), sus resultados, las estrategias aplicadas en el pasado y las lecciones aprendidas. Esta reseña permite inferir acerca de la factibilidad de implementar esta aproximación en la Argentina, y que el mismo pueda ser sostenidos en el tiempo y que sea integrados entre distintas disciplinas y tomadores de decisiones. Se concluye que existe un potencial actual y grandes oportunidades a futuro para poder consolidar una red del tipo LTER/LTSER en Argentina