Dysregulation of innate immune signaling in animal models of spinal muscular atrophy.

BACKGROUND: Spinal muscular atrophy (SMA) is a devastating neuromuscular disease caused by hypomorphic loss of function in the survival motor neuron (SMN) protein. SMA presents across a broad spectrum of disease severity. Unfortunately, genetic models of intermediate SMA have been difficult to generate in vertebrates and are thus unable to address key aspects of disease etiology. To address these issues, we developed a Drosophila model system that recapitulates the full range of SMA severity, allowing studies of pre-onset biology as well as late-stage disease processes. RESULTS: Here, we carried out transcriptomic and proteomic profiling of mild and intermediate Drosophila models of SMA to elucidate molecules and pathways that contribute to the disease. Using this approach, we elaborated a role for the SMN complex in the regulation of innate immune signaling. We find that mutation or tissue-specific depletion of SMN induces hyperactivation of the immune deficiency (IMD) and Toll pathways, leading to overexpression of antimicrobial peptides (AMPs) and ectopic formation of melanotic masses in the absence of an external challenge. Furthermore, the knockdown of downstream targets of these signaling pathways reduced melanotic mass formation caused by SMN loss. Importantly, we identify SMN as a negative regulator of a ubiquitylation complex that includes Traf6, Bendless, and Diap2 and plays a pivotal role in several signaling networks. CONCLUSIONS: In alignment with recent research on other neurodegenerative diseases, these findings suggest that hyperactivation of innate immunity contributes to SMA pathology. This work not only provides compelling evidence that hyperactive innate immune signaling is a primary effect of SMN depletion, but it also suggests that the SMN complex plays a regulatory role in this process in vivo. In summary, immune dysfunction in SMA is a consequence of reduced SMN levels and is driven by cellular and molecular mechanisms that are conserved between insects and mammals.

Randomized Controlled Trial of the Effect of an Exercise Rehabilitation Program on Symptom Burden in Maintenance Hemodialysis: A Clinical Research Protocol.

Background: People receiving hemodialysis experience high symptom burden that contributes to low functional status and poor health-related quality of life. Management of symptoms is a priority for individuals receiving hemodialysis but limited effective treatments exist. There is emerging evidence that exercise programming can improve several common dialysis-related symptoms. Objective: The primary aim of this study is to evaluate the effect of an exercise rehabilitation program on symptom burden in individuals receiving maintenance hemodialysis. Design: Multicenter, randomized controlled, 1:1 parallel, open label, prospective blinded end point trial. Setting: Three facility-based hemodialysis units in Winnipeg, Manitoba, Canada. Participants: Adults aged 18 years or older with end-stage kidney disease receiving facility-based maintenance hemodialysis for more than 3 months, with at least 1 dialysis-related symptom as indicated by the Dialysis Symptom Index (DSI) severity score >0 (n = 150). Intervention: Supervised 26-week exercise rehabilitation program and 60 minutes of cycling during hemodialysis thrice weekly. Exercise intensity and duration were supervised and individualized by the kinesiologist as per participant baseline physical function with gradual progression over the course of the intervention. Control: Usual hemodialysis care (no exercise program). Measurements: Our primary outcome is change in symptom burden at 12 weeks as measured by the DSI severity score. Secondary outcomes include change in modified DSI severity score (includes 10 symptoms most plausible to improve with exercise), change in DSI severity score at 26 and 52 weeks; time to recover post-hemodialysis; health-related quality of life measured using EuroQol (EQ)-5D-5L; physical activity behavior measured by self-report (Godin-Shepherd questionnaire) and triaxial accelerometry; exercise capacity (shuttle walk test); frailty (Fried); self-efficacy for exercise; and 1-year hospitalization and mortality. Methods: Change in primary outcome will be compared between groups by independent 2-tailed t test or Mann-Whitney U test depending on data distribution and using generalized linear mixed models, with study time point as a random effect and adjusted for baseline DSI score. Similarly, change in secondary outcomes will be compared between groups over time using appropriate parametric and nonparametric statistical tests depending on data type and distribution. Limitations: The COVID-19 pandemic restrictions on clinical research at our institution delayed completion of target recruitment and prevented collection of accelerometry and physical function outcome data for 15 months until restrictions were lifted. Conclusions: The application of an exercise rehabilitation program to improve symptom burden in individuals on hemodialysis may ameliorate common symptoms observed in individuals on hemodialysis and result in improved quality of life and reduced disability and morbidity over the long term. Importantly, this pragmatic study, with a standardized exercise intervention that is adaptable to baseline physical function, addresses an important gap in both clinical care of hemodialysis patients and our current knowledge.

Contexte: Les personnes sous hémodialyse éprouvent un grand nombre de symptômes qui contribuent à un faible état fonctionnel et à une mauvaise qualité de vie liée à la santé. La prise en charge des symptômes est une priorité pour les personnes sous hémodialyse, mais les traitements efficaces sont limités. De nouvelles preuves montrent que l'adoption d'un programme d'exercice permettrait d'améliorer plusieurs symptômes courants liés à la dialyse. Objectifs: Le principal objectif de cette étude est d'évaluer l'effet d'un programme de rééducation par l'exercice sur le fardeau des symptômes chez les personnes recevant une hémodialyse d'entretien. Conception: Essai clinique prospectif randomisé-contrôlé, en aveugle, en parallèle 1:1 et ouvert, multicentrique. Cadre: Trois unités d'hémodialyse de Winnipeg, au Manitoba (Canada). Sujets: Des adultes atteints d'insuffisance rénale terminale qui reçoivent des traitements d'hémodialyse d'entretien en centre depuis plus de trois mois et qui présentent au moins un symptôme lié à la dialyse, tel qu'indiqué par un score de gravité de l'indice des symptômes de la dialyse (Dialysis Symptom Index) supérieur à zéro (n = 150). Intervention: Programme supervisé de rééducation par l'exercice d'une durée de 26 semaines et 60 minutes de vélo trois fois par semaine pendant l'hémodialyse. L'intensité et la durée de l'exercice ont été supervisées par un kinésiologue qui les a ensuite personnalisées en fonction de la forme physique initiale du participant en prévoyant une progression graduelle tout au long de l'intervention. Groupe témoin: Soins habituels d'hémodialyse (sans programme d'exercice). Mesures: Notre principal critère de jugement est un changement dans le fardeau lié aux symptômes après 12 semaines, tel que mesuré par le score de gravité de l'indice des symptômes de dialyse (ISD). Les critères d'évaluation secondaires comprennent un changement du score modifié de gravité de l'ISD (portant sur 10 symptômes les plus plausibles de s'améliorer avec l'exercice), la modification du score de gravité de l'ISD après 26 et 52 semaines, le temps de récupération après l'hémodialyse, la qualité de vie liée à la santé mesurée par le questionnaire EQ5D-5L, le comportement lié à l'activité physique mesuré par autoévaluation (questionnaire Godin-Shepherd) et par accéléromètre triaxial, la capacité d'effort (test de marche navette), la fragilité (Fried), le sentiment d'efficacité autodéclaré face à l'exercice, ainsi que les hospitalisations et la mortalité à un an. Méthodologie: Les changements pour le principal critère de jugement seront comparés entre les groupes par un test t bilatéral indépendant ou un test U de Mann-Whitney en fonction de la distribution des données, ainsi qu'à l'aide de modèles linéaires mixtes généralisés avec un point temporel de l'étude comme effet aléatoire et corrigé en fonction du score ISD initial. Les changements dans les résultats secondaires seront comparés entre les groupes au fil du temps à l'aide des tests statistiques paramétriques et non paramétriques appropriés selon le type de données et la distribution. Limites: Les restrictions liées à la pandémie de COVID-19 dans notre établissement ont retardé le recrutement des cibles et empêché pendant 15 mois la collecte de données sur les résultats mesurés par l'accéléromètre et les mesures de la fonction physique, soit jusqu'à ce que les restrictions soient levées. Conclusion: L'adoption d'un programme de rééducation par l'exercice visant à réduire le fardeau lié aux symptômes chez les personnes sous hémodialyse peut améliorer les symptômes courants observés dans cette population et se traduire par une amélioration de la qualité de vie et une réduction de l'invalidité et de la morbidité à long terme. Il convient de noter que cet essai pragmatique, avec son intervention d'exercice standardisée adaptable à la condition physique initiale de la personne, comble une lacune importante dans les soins cliniques des patients sous hémodialyse et dans nos connaissances actuelles.

A Randomized Trial Examining the Impact of Timing of Intradialytic Cycling on Intradialytic Hypotension.

Introduction: Intradialytic cycling is often performed during the first half of hemodialysis because of concerns regarding increased frequency of intradialytic hypotension (IDH) late in hemodialysis. This increases exercise program resource needs and limits utility of intradialytic cycling to treat dialysis-related symptoms. Methods: This multicenter, randomized, crossover trial compared IDH rate when cycling during the first half versus the second half of hemodialysis in 98 adults on maintenance hemodialysis. Group A cycled during the first half of hemodialysis for 2 weeks and subsequently during the second half for 2 weeks. In group B, the cycling schedule was reversed. Blood pressure (BP) was measured every 15 minutes throughout hemodialysis. Primary outcome was IDH rate (systolic BP [SBP] decrease of >20 mm Hg or SBP <90 mm Hg). Secondary outcomes included symptomatic IDH rate and time to recover post hemodialysis. Data were analyzed using negative binomial and gamma distribution mixed regression. Results: Mean age 64.7 (SD 12.0) and 64.7 (SD 14.2) years in group A (n = 52) and group B (n = 46), respectively. Proportions of females were 33% in group A and 43% in group B. Median time on hemodialysis was 4.1 (interquartile range [IQR] 2.5, 6.1]) years in group A and 3.9 years (IQR 2.5, 6.7) in group B. IDH rate per 100 hemodialysis hours (95% confidence interval [CI]) was 34.2 (26.4, 42.0) and 36.0 (28.9, 43.1) during early and late intradialytic cycling, respectively (P = 0.53). Timing of intradialytic cycling was not associated with symptomatic IDH (relative risk [RR]: 1.07 [0.75-1.53]) or time to recover post hemodialysis (odds ratio: 0.99 [0.79-1.23]). Conclusion: We found no association between the rate of overall or symptomatic IDH and the timing of intradialytic cycling in patients enrolled in an intradialytic cycling program. Increased use of cycling late in hemodialysis may optimize intradialytic cycling program resource use and should be studied as a possible treatment for symptoms common in late hemodialysis.

The practice and promise of temporal genomics for measuring evolutionary responses to global change.

Understanding the evolutionary consequences of anthropogenic change is imperative for estimating long-term species resilience. While contemporary genomic data can provide us with important insights into recent demographic histories, investigating past change using present genomic data alone has limitations. In comparison, temporal genomics studies, defined herein as those that incorporate time series genomic data, utilize museum collections and repeated field sampling to directly examine evolutionary change. As temporal genomics is applied to more systems, species and questions, best practices can be helpful guides to make the most efficient use of limited resources. Here, we conduct a systematic literature review to synthesize the effects of temporal genomics methodology on our ability to detect evolutionary changes. We focus on studies investigating recent change within the past 200 years, highlighting evolutionary processes that have occurred during the past two centuries of accelerated anthropogenic pressure. We first identify the most frequently studied taxa, systems, questions and drivers, before highlighting overlooked areas where further temporal genomic studies may be particularly enlightening. Then, we provide guidelines for future study and sample designs while identifying key considerations that may influence statistical and analytical power. Our aim is to provide recommendations to a broad array of researchers interested in using temporal genomics in their work.

Dysregulation of innate immune signaling in animal models of Spinal Muscular Atrophy.

Background: Spinal Muscular Atrophy (SMA) is a devastating neuromuscular disease caused by hypomorphic loss of function in the Survival Motor Neuron (SMN) protein. SMA presents across broad spectrum of disease severity. Unfortunately, vertebrate models of intermediate SMA have been difficult to generate and are thus unable to address key aspects of disease etiology. To address these issues, we developed a Drosophila model system that recapitulates the full range of SMA severity, allowing studies of pre-onset biology as well as late-stage disease processes. Results: Here, we carried out transcriptomic and proteomic profiling of mild and intermediate Drosophila models of SMA to elucidate molecules and pathways that contribute to the disease. Using this approach, we elaborated a role for the SMN complex in the regulation of innate immune signaling. We find that mutation or tissue-specific depletion of SMN induces hyperactivation of the Immune Deficiency (IMD) and Toll pathways, leading to overexpression of antimicrobial peptides (AMPs) and ectopic formation of melanotic masses in the absence of an external challenge. Furthermore, knockdown of downstream targets of these signaling pathways reduced melanotic mass formation caused by SMN loss. Importantly, we identify SMN as a negative regulator of an ubiquitylation complex that includes Traf6, Bendless and Diap2, and plays a pivotal role in several signaling networks. Conclusions: In alignment with recent research on other neurodegenerative diseases, these findings suggest that hyperactivation of innate immunity contributes to SMA pathology. This work not only provides compelling evidence that hyperactive innate immune signaling is a primary effect of SMN depletion, but it also suggests that the SMN complex plays a regulatory role in this process in vivo. In summary, immune dysfunction in SMA is a consequence of reduced SMN levels and is driven by cellular and molecular mechanisms that are conserved between insects and mammals.

Voice spoofing detection using a neural networks assembly considering spectrograms and mel frequency cepstral coefficients.

Nowadays, biometric authentication has gained relevance due to the technological advances that have allowed its inclusion in many daily-use devices. However, this same advantage has also brought dangers, as spoofing attacks are now more common. This work addresses the vulnerabilities of automatic speaker verification authentication systems, which are prone to attacks arising from new techniques for the generation of spoofed audio. In this article, we present a countermeasure for these attacks using an approach that includes easy to implement feature extractors such as spectrograms and mel frequency cepstral coefficients, as well as a modular architecture based on deep neural networks. Finally, we evaluate our proposal using the well-know ASVspoof 2017 V2 database, the experiments show that using the final architecture the best performance is obtained, achieving an equal error rate of 6.66% on the evaluation set.

Allele-specific alternative splicing of Drosophila Ribosomal protein S21 suppresses a lethal mutation in the Phosphorylated adaptor for RNA export (Phax) gene.

Genetic disruptions to the biogenesis of spliceosomal small-nuclear ribonucleoproteins in Drosophila cause wide-spread alternative splicing changes, including changes to the splicing of pre-mRNA for Ribosomal protein S21 (RpS21). Using a transposon mutant for the Phosphorylated adaptor for RNA export (Phax) gene, we demonstrate that changes in the splicing of RpS21 transcripts have a strong influence on the developmental progression of PhaxSH/SH mutants. Different alleles of the Drosophila RpS21 gene are circulating in common laboratory strains and cell lines. These alleles exhibit differences in RpS21 intron retention and splicing efficiency. Differences in the splicing of RpS21 transcripts account for prior conflicting observations of the phenotypic severity of PhaxSH/SH mutant stocks. The alleles uncover a strong splicing enhancer in RpS21 transcripts that can fully suppress the larval lethality and partially suppress the pupal lethality exhibited by PhaxSH/SH mutant lines. In the absence of the splicing enhancer, the splicing of RpS21 transcripts can be modulated in trans by the SR-rich B52 splicing factor. As PhaxSH/SH mutants exhibit wide-spread splicing changes in transcripts for other genes, findings here establish the importance of a single alternative splicing event, RpS21 splicing or intron retention, to the developmental progression of Drosophila.

Piperidine-Iodine as Efficient Dual Catalyst for the One-Pot, Three-Component Synthesis of Coumarin-3-Carboxamides.

A simple and efficient one-pot, three-component synthetic method for the preparation of coumarin-3-carboxamides was carried out by the reaction of salicylaldehyde, aliphatic primary/secondary amines, and diethylmalonate. The protocol employs piperidine-iodine as a dual system catalyst and ethanol, a green solvent. The main advantages of this approach are that it is a metal-free and clean reaction, has low catalyst loading, and requires no tedious workup.

Nests of dividing neuroblasts sustain interneuron production for the developing human brain.

The human cortex contains inhibitory interneurons derived from the medial ganglionic eminence (MGE), a germinal zone in the embryonic ventral forebrain. How this germinal zone generates sufficient interneurons for the human brain remains unclear. We found that the human MGE (hMGE) contains nests of proliferative neuroblasts with ultrastructural and transcriptomic features that distinguish them from other progenitors in the hMGE. When dissociated hMGE cells are transplanted into the neonatal mouse brain, they reform into nests containing proliferating neuroblasts that generate young neurons that migrate extensively into the mouse forebrain and mature into different subtypes of functional interneurons. Together, these results indicate that the nest organization and sustained proliferation of neuroblasts in the hMGE provide a mechanism for the extended production of interneurons for the human forebrain.

Set4 regulates stress response genes and coordinates histone deacetylases within yeast subtelomeres.

The yeast chromatin protein Set4 is a member of the Set3-subfamily of SET domain proteins which play critical roles in the regulation of gene expression in diverse developmental and environmental contexts. We previously reported that Set4 promotes survival during oxidative stress and regulates expression of stress response genes via stress-dependent chromatin localization. In this study, global gene expression analysis and investigation of histone modification status identified a role for Set4 in maintaining gene repressive mechanisms within yeast subtelomeres under both normal and stress conditions. We show that Set4 works in a partially overlapping pathway to the SIR complex and the histone deacetylase Rpd3 to maintain proper levels of histone acetylation and expression of stress response genes encoded in subtelomeres. This role for Set4 is particularly critical for cells under hypoxic conditions, where the loss of Set4 decreases cell fitness and cell wall integrity. These findings uncover a new regulator of subtelomeric chromatin that is key to stress defense pathways and demonstrate a function for Set4 in regulating repressive, heterochromatin-like environments.

Adaptive local false discovery rate procedures for highly spiky data and their application RNA sequencing data of yeast SET4 deletion mutants.

Chromatin dynamics are central to the regulation of gene expression and genome stability. In order to improve understanding of the factors regulating chromatin dynamics, the genes encoding these factors are deleted and the differential gene expression profiles are determined using approaches such as RNA sequencing. Here, we analyzed a gene expression dataset aimed at uncovering the function of the relatively uncharacterized chromatin regulator, Set4, in the model system Saccharomyces cerevisiae (budding yeast). The main theme of this paper focuses on identifying the highly differentially expressed genes in cells deleted for Set4 (referred to as Set4 Δ mutant dataset) compared to the wild-type yeast cells. The Set4 Δ mutant data produce a spiky distribution on the log-fold changes of their expressions, and it is reasonably assumed that genes which are not highly differentially expressed come from a mixture of two normal distributions. We propose an adaptive local false discovery rate (FDR) procedure, which estimates the null distribution of the log-fold changes empirically. We numerically show that, unlike existing approaches, our proposed method controls FDR at the aimed level (0.05) and also has competitive power in finding differentially expressed genes. Finally, we apply our procedure to analyzing the Set4 Δ mutant dataset.

Haplotype network branch diversity, a new metric combining genetic and topological diversity to compare the complexity of haplotype networks.

A common way of illustrating phylogeographic results is through the use of haplotype networks. While these networks help to visualize relationships between individuals, populations, and species, evolutionary studies often only quantitatively analyze genetic diversity among haplotypes and ignore other network properties. Here, we present a new metric, haplotype network branch diversity (HBd), as an easy way to quantifiably compare haplotype network complexity. Our metric builds off the logic of combining genetic and topological diversity to estimate complexity previously used by the published metric haplotype network diversity (HNd). However, unlike HNd which uses a combination of network features to produce complexity values that cannot be defined in probabilistic terms, thereby obscuring the values' implication for a sampled population, HBd uses frequencies of haplotype classes to incorporate topological information of networks, keeping the focus on the population and providing easy-to-interpret probabilistic values for randomly sampled individuals. The goal of this study is to introduce this more intuitive metric and provide an R script that allows researchers to calculate diversity and complexity indices from haplotype networks. A group of datasets, generated manually (model dataset) and based on published data (empirical dataset), were used to illustrate the behavior of HBd and both of its terms, haplotype diversity, and a new index called branch diversity. Results followed a predicted trend in both model and empirical datasets, from low metric values in simple networks to high values in complex networks. In short, the new combined metric joins genetic and topological diversity of haplotype networks, into a single complexity value. Based on our analysis, we recommend the use of HBd, as it makes direct comparisons of network complexity straightforward and provides probabilistic values that can readily discriminate situations that are difficult to resolve with available metrics.

A novel method of screening combinations of angiostatics identifies bevacizumab and temsirolimus as synergistic inhibitors of glioma-induced angiogenesis.

Tumor angiogenesis is critical for the growth and progression of cancer. As such, angiostasis is a treatment modality for cancer with potential utility for multiple types of cancer and fewer side effects. However, clinical success of angiostatic monotherapies has been moderate, at best, causing angiostatic treatments to lose their early luster. Previous studies demonstrated compensatory mechanisms that drive tumor vascularization despite the use of angiostatic monotherapies, as well as the potential for combination angiostatic therapies to overcome these compensatory mechanisms. We screened clinically approved angiostatics to identify specific combinations that confer potent inhibition of tumor-induced angiogenesis. We used a novel modification of the ex ovo chick chorioallantoic membrane (CAM) model that combined confocal and automated analyses to quantify tumor angiogenesis induced by glioblastoma tumor onplants. This model is advantageous due to its low cost and moderate throughput capabilities, while maintaining complex in vivo cellular interactions that are difficult to replicate in vitro. After screening multiple combinations, we determined that glioblastoma-induced angiogenesis was significantly reduced using a combination of bevacizumab (Avastin®) and temsirolimus (Torisel®) at doses below those where neither monotherapy demonstrated activity. These preliminary results were verified extensively, with this combination therapy effective even at concentrations further reduced 10-fold with a CI value of 2.42E-5, demonstrating high levels of synergy. Thus, combining bevacizumab and temsirolimus has great potential to increase the efficacy of angiostatic therapy and lower required dosing for improved clinical success and reduced side effects in glioblastoma patients.

Análisis de la prevalencia y principales factores de riesgo asociados a la retinopatía diabética / Analysis of the prevalence and major risk factors associated with diabetic retinopathy

No disponible

Patterns of Genomic Divergence and Signals of Selection in Sympatric and Allopatric Northeastern Pacific and Sea of Cortez Populations of the Sargo (Anisotremus davidsonii) and Longjaw Mudsucker (Gillichthys mirabilis).

Studying how isolation can impact population divergence and adaptation in co-distributed species can bring us closer to understanding how landscapes affect biodiversity. The Sargo, Anisotremus davidsonii (Haemulidae), and the Longjaw mudsucker, Gillichthys mirabilis (Gobiidae), offer a notable framework to study such mechanisms as their Pacific populations cross phylogeographic breaks at Point Conception, California, United States, and Punta Eugenia, Mexico, and are separated to those in the Sea of Cortez by the Baja California peninsula. Here, thousands of loci are genotyped from 48 Sargos and 73 mudsuckers using RADseq to characterize overall genomic divergence, and search for common patterns of putatively neutral and non-neutral structure based on outlier loci among populations with hypothesized different levels of isolation. We further search for parallels between population divergence and the total proportion of outliers, outlier FST distribution, and the proportion of outliers matching coding regions in GenBank. Statistically significant differentiation is seen across Point Conception in mudsucker (FST = 0.15), Punta Eugenia in Sargo (FST = 0.02), and on either side of the Baja California peninsula in both species (FST = 0.11 and 0.23, in Sargo and mudsucker, respectively). Each species shows structure using neutral and non-neutral loci. Finally, higher population divergence yields a more even distribution of outliers along their differentiation range but does not always translate into higher outlier proportions or higher rates in which outliers are matched to coding regions. If repeated in similar systems, observed genomic patterns might reveal speciation signatures in diverse networks of population isolation.

Identification of COVID-19 Spreaders Using Multiplex Networks Approach.

In this work, we present a methodology to identify COVID-19 spreaders using the analysis of the relationship between socio-cultural and economic characteristics with the number of infections and deaths caused by the COVID-19 virus in different countries. For this, we analyze the information of each country using the complex networks approach, specifically by analyzing the spreaders countries based on the separator set in 5-layer multiplex networks. The results show that, we obtain a classification of the countries based on their numerical values in socioeconomics, population, Gross Domestic Product (GDP), health and air connections; where, in the spreader set there are those countries that have high, medium or low values in the different characteristics; however, the aspect that all the countries belonging to the separator set share is a high value in air connections.

Artritis Gotosa. 10 años de Seguimiento / Artritis Gotosa. 10 años de Seguimiento

Introduction: gouty arthritis is a persistent metabolic disease that produces an increase of the circulating uric acid, with the resulting deposit of monosodic urate crystals in the tissues. Objective: to characterize patients with gouty arthritis clinically and epidemiologically. Methods: a descriptive investigation of 72 patients with a diagnosis of gouty arthritis, assisted at Arnaldo Milián Castro Clinical Surgical University Hospital was carried out from January 2008 to December 2017. Results: patients between 40 and 49 years of age were the most representative group with a highest incidence in not white patients and the male sex. Obesity and hypertension prevailed as previous personal antecedents. Alcohol intake was the most represented toxic habit. A crisis of inflammation of the big toe was the more frequent starting manifestation. Swelling of soft tissues was the main radiologic alteration. Conclusion: gouty arthritis is present with a highest frequency in the male sex with a peak of incidence in the fourth decade of life. It is associated to bad diet habits and alcohol intake that could cause joint damage(AU)

Introducción: la artritis gotosa es una enfermedad metabólica persistente, que produce un aumento del ácido úrico circulante, con el consiguiente depósito de cristales de uratos monosódicos en los tejidos. Objetivo: caracterizar clínica y epidemiológicamente a los pacientes con artritis gotosa. Método: se realizó una investigación descriptiva de 72 pacientes con diagnóstico de artritis gotosa, atendidos en el Hospital Universitario Clínico Quirúrgico Arnaldo Milián Castro, entre enero del 2008 y diciembre del 2017. Resultados: los pacientes entre 40 y 49 años de edad fueron los más representativos, con mayor incidencia en no blancos y del sexo masculino. Predominó la obesidad y la hipertensión arterial como antecedentes patológicos personales. El alcohol fue el hábito tóxico mayoritariamente representado. La crisis de podagra resulto ser la manifestación inicial más usual. El aumento de partes blandas fue la principal alteración radiológica. Conclusiones: La gota se presenta con mayor frecuencia en el sexo masculino con un pico de incidencia en la cuarta década de la vida. Está asociada a malos hábitos dietéticos y al consumo de bebidas alcohólicas pudiendo ocasionar daño articular(AU)

Influence of Gut Microbiota on Progression to Tuberculosis Generated by High Fat Diet-Induced Obesity in C3HeB/FeJ Mice.

The administration of a high fat content diet is an accelerating factor for metabolic syndrome, impaired glucose tolerance, and early type 2 diabetes. The present study aims to assess the impact of a high fat diet on tuberculosis progression and microbiota composition in an experimental animal model using a C3HeB/FeJ mouse strain submitted to single or multiple consecutive aerosol infections. These models allowed us to study the protection induced by Bacillus Calmette-Guérin vaccination as well as by the natural immunity induced by chemotherapy after a low dose Mycobacterium tuberculosis infection. Our results show that a high fat diet is able to trigger a pro-inflammatory response, which results in a faster progression toward active tuberculosis and an impaired protective effect of BCG vaccination, which is not the case for natural immunity. This may be related to dysbiosis and a reduction in the Firmicutes/Bacteroidetes ratio in the gut microbiota caused by a decrease in the abundance of the Porphyromonadaceae family and, in particular, the Barnesiella genus. It should also be noted that a high fat diet is also related to an increase in the genera Alistipes, Parasuterella, Mucispirillum, and Akkermansia, which have previously been related to dysbiotic processes. As diabetes mellitus type 2 is a risk factor for developing tuberculosis, these findings may prove useful in the search for new prophylactic strategies for this population subset.