Physical activity modify skeletal muscle fiber types in an animal model of metabolic syndrome

Metabolic Syndrome (MetS) is a cluster of clinical conditions, associated to an increased cardiovascular risk, as well as to hypogonadism in males. Lifestyle modification (including physical exercise, PhyEx) may be beneficial for the condition. Skeletal muscles (SkM) are some of the most highly plastic tissues, able of remodeling in response to use, disuse and disease. In particular, transformations of fiber type may occur in response to physiological milieu to induce functional adaptations. This study is aimed at investigating in experimental MetS, high fat diet-induced in male rabbits [1], the effect of PhyEx on hormonal and metabolic parameters, as well as on SkM composition. Control and MetS rabbits were exercise-trained to run on a treadmill for 12 weeks. Quadriceps femoris samples were collected for histomorphological and gene expression analyses. We found that exercise resistance was significantly reduced in MetS rabbits, as demonstrated by the significant reduction of both running time and distance, compared to control group. MetS rabbits also exhibited the lowest quadriceps mass. Fiber typing by PAS-staining showed a pronounced shift from slower type I to faster type II fibers in MetS group in response to PhysEx, suggesting that MetS condition addressed SkM function towards anaerobic metabolism. Accordingly, extracellular lactate levels were significantly increased and mitochondrial respiration-related genes reduced in SkM of MetS rabbits respect to controls. Interestingly, PhyEx significantly counteracted MetS-related testosterone deficiency and hypercholesterolemia. In conclusion, our results indicate that dysmetabolic milieu induces a reduced proportion of fatigue-resistant type I fibers in response to PhysEx, which however resulted beneficial for MetS condition

European Committee for Treatment and Research in Multiple Sclerosis and European Academy of Neurology consensus on vaccination in people with multiple sclerosis: Improving immunization strategies in the era of highly active immunotherapeutic drugs

Background and purpose: With the new highly active drugs available for people with multiple sclerosis (pwMS), vaccination becomes an essential part of the risk management strategy. We aimed to develop a European evidence-based consensus for the vaccination strategy of pwMS who are candidates for disease-modifying therapies (DMTs).Methods: This work was conducted by a multidisciplinary working group using formal consensus methodology. Clinical questions (defined as population, interventions and outcomes) considered all authorized DMTs and vaccines. A systematic literature search was conducted and quality of evidence was defined according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. The recommendations were formulated based on the quality of evidence and the risk-benefit balance.Results: Seven questions, encompassing vaccine safety, vaccine effectiveness, global vaccination strategy and vaccination in subpopulations (pediatric, pregnant women, elderly and international travelers) were considered. A narrative description of the evidence considering published studies, guidelines and position statements is presented. A total of 53 recommendations were agreed by the working group after three rounds of consensus.Conclusion: This first European consensus on vaccination in pwMS proposes the best vaccination strategy according to current evidence and expert knowledge, with the goal of homogenizing the immunization practices in pwMS

ECTRIMS/EAN consensus on vaccination in people with multiple sclerosis: Improving immunization strategies in the era of highly active immunotherapeutic drugs

Background: With the new highly active drugs available for people with multiple sclerosis (pwMS), vaccination becomes an essential part of the risk management strategy Objective: To develop a European evidence-based consensus for the vaccination strategy of pwMS who are candidates for disease-modifying therapies (DMTs). Methods: This work was conducted by a multidisciplinary working group using formal consensus methodology. Clinical questions (defined as population, interventions, and outcomes) considered all authorized DMTs and vaccines. A systematic literature search was conducted and quality of evidence was defined according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. The recommendations were formulated based on the quality of evidence and the risk-benefit balance. Results: Seven questions, encompassing vaccine safety, vaccine effectiveness, global vaccination strategy and vaccination in sub-populations (pediatric, pregnant women, elderly and international travelers) were considered. A narrative description of the evidence considering published studies, guidelines, and position statements is presented. A total of 53 recommendations were agreed by the working group after three rounds of consensus. Conclusion: This first European consensus on vaccination in pwMS proposes the best vaccination strategy according to current evidence and expert knowledge, with the goal of homogenizing the immunization practices in pwMS

Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions

Contribution of Rare and Low-Frequency Variants to Multiple Sclerosis Susceptibility in the Italian Continental Population

Genome-wide association studies identified over 200 risk loci for multiple sclerosis (MS) focusing on common variants, which account for about 50% of disease heritability. The goal of this study was to investigate whether low-frequency and rare functional variants, located in MS-established associated loci, may contribute to disease risk in a relatively homogeneous population, testing their cumulative effect (burden) with gene-wise tests. We sequenced 98 genes in 588 Italian patients with MS and 408 matched healthy controls (HCs). Variants were selected using different filtering criteria based on allelic frequency and in silico functional impacts. Genes showing a significant burden (n = 17) were sequenced in an independent cohort of 504 MS and 504 HC. The highest signal in both cohorts was observed for the disruptive variants (stop-gain, stop-loss, or splicing variants) located in EFCAB13, a gene coding for a protein of an unknown function (p < 10(-4)). Among these variants, the minor allele of a stop-gain variant showed a significantly higher frequency in MS versus HC in both sequenced cohorts (p = 0.0093 and p = 0.025), confirmed by a meta-analysis on a third independent cohort of 1298 MS and 1430 HC (p = 0.001) assayed with an SNP array. Real-time PCR on 14 heterozygous individuals for this variant did not evidence the presence of the stop-gain allele, suggesting a transcript degradation by non-sense mediated decay, supported by the evidence that the carriers of the stop-gain variant had a lower expression of this gene (p = 0.0184). In conclusion, we identified a novel low-frequency functional variant associated with MS susceptibility, suggesting the possible role of rare/low-frequency variants in MS as reported for other complex diseases