The Helicobacter pylori Genome Project : insights into H. pylori population structure from analysis of a worldwide collection of complete genomes

Helicobacter pylori, a dominant member of the gastric microbiota, shares co-evolutionary history with humans. This has led to the development of genetically distinct H. pylori subpopulations associated with the geographic origin of the host and with differential gastric disease risk. Here, we provide insights into H. pylori population structure as a part of the Helicobacter pylori Genome Project (HpGP), a multi-disciplinary initiative aimed at elucidating H. pylori pathogenesis and identifying new therapeutic targets. We collected 1011 well-characterized clinical strains from 50 countries and generated high-quality genome sequences. We analysed core genome diversity and population structure of the HpGP dataset and 255 worldwide reference genomes to outline the ancestral contribution to Eurasian, African, and American populations. We found evidence of substantial contribution of population hpNorthAsia and subpopulation hspUral in Northern European H. pylori. The genomes of H. pylori isolated from northern and southern Indigenous Americans differed in that bacteria isolated in northern Indigenous communities were more similar to North Asian H. pylori while the southern had higher relatedness to hpEastAsia. Notably, we also found a highly clonal yet geographically dispersed North American subpopulation, which is negative for the cag pathogenicity island, and present in 7% of sequenced US genomes. We expect the HpGP dataset and the corresponding strains to become a major asset for H. pylori genomics

Percepción de la calidad del servicio en un centro de atención primaria de salud chileno

The objectives of this research were to quantify the perception of three segments of users who received medical attention in a family health center and to analyze the existence of underlying quality dimensions. The justification is the need to improve service attention and decision making process. The methodology used a randomized survey applied to users who received medical attention in a primary health care center in the commune of Coihueco, Chile. In addition, the univariate analysis was used to quantify perceptions and the factor analysis technique to identify underlying dimensions. The results indicated that the overall quality level of the medical services received by users was 4,05 on an evaluation scale of one to five points and, five underlying quality dimensions were identified among the three user segments. By way of conclusions, it was determined that people equal to or older than 45 years had a higher level of satisfaction with respect to people under 19 and people between 20 and 44 years. In addition, it was possible to distinguish five underlying dimensions among the three segments of users: Respect for the patient, Accessibility of the service, Pleasant environment, Service availability and Tolerance towards the patientLos objetivos de esta investigación fueron cuantificar la percepción de tres segmentos de usuarios que recibieron atención médica en un centro de salud familiar y, analizar la existencia de dimensiones de calidad subyacentes. La justificación es la necesidad de mejorar la atención del servicio y proceso de toma de decisiones. La metodología utilizó una encuesta aleatoria aplicada a usuarios que recibieron atención médica en un centro de salud de atención primaria de la comuna de Coihueco, Chile, además, se utilizó el análisis univariado para cuantificar percepciones y la técnica de análisis de factores para identificar dimensiones subyacentes. Los resultados indicaron que el nivel de calidad global de los servicios médicos recibidos por los usuarios fue de 4,05 en una escala de evaluación de uno a cinco puntos y, se identificaron cinco dimensiones de calidad subyacentes entre los tres segmentos de usuarios., se determinó que las personas iguales o mayores de 45 años presentaron un nivel de satisfacción mayor respecto de las personas menores de 19 años y personas entre 20 y 44 años. Además, se lograron distinguir cinco dimensiones subyacentes entre los tres segmentos de usuarios: Respeto hacia el paciente, accesibilidad del servicio, entorno agradable, accesibilidad del servicio, disponibilidad del servicio y tolerancia hacia el pacient

Repurposing doxycycline for synucleinopathies: Remodelling of α-synuclein oligomers towards non-toxic parallel beta-sheet structured species

Synucleinophaties are progressive neurodegenerative disorders with no cure to date. An attractive strategy to tackle this problem is repurposing already tested safe drugs against novel targets. In this way, doxycycline prevents neurodegeneration in Parkinson models by modulating neuroinflammation. However, anti-inflammatory therapy per se is insufficient to account for neuroprotection. Herein we characterise novel targets of doxycycline describing the structural background supporting its effectiveness as a neuroprotector at subantibiotic doses. Our results show that doxycycline reshapes α-synuclein oligomers into off-pathway, high-molecular-weight species that do not evolve into fibrils. Off-pathway species present less hydrophobic surface than on-pathway oligomers and display different β-sheet structural arrangement. These structural changes affect the α-synuclein ability to destabilize biological membranes, cell viability, and formation of additional toxic species. Altogether, these mechanisms could act synergically giving novel targets for repurposing this drug.Fil: González Lizarraga, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universite Pierre et Marie Curie; Francia. Centre de Recherche de I'Institut du Cerveau et de la Moelle Epinière; FranciaFil: Socias, Sergio Benjamin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Avila, Cesar Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Torres Bugeau, Clarisa Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Barbosa, Leandro R. S.. Universidade de Sao Paulo; BrasilFil: Binolfi, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; ArgentinaFil: Sepúlveda Díaz, Julia E.. Centre de Recherche de I'Institut du Cerveau et de la Moelle Epinière; Francia. Universite Pierre et Marie Curie; FranciaFil: Del Bel, Elaine. Universidade de Sao Paulo; BrasilFil: Fernandez, Claudio Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; ArgentinaFil: Garcia Orozco Ep Papy, Dulce Maria. Centre National de la Recherche Scientifique; Francia. Université Paris-Est Créteil; FranciaFil: Itri, Rosangela. Universidade de Sao Paulo; BrasilFil: Raisman Vozari, Rita. Centre National de la Recherche Scientifique; Francia. Centre de Recherche de I'Institut du Cerveau et de la Moelle Epinière; Francia. Universite Pierre et Marie Curie; FranciaFil: Chehin, Rosana Nieves. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentin

Impact of an exercise program on acylcarnitines in obesity: a prospective controlled study

<p>Abstract</p> <p>Background</p> <p>Acylcarnitine (AC) transport dysfunction into the mitochondrial matrix is one of the pathophysiological mechanisms of type 2 diabetes mellitus (DM). The effect of an aerobic exercise (AE) program on this condition in obese subjects without DM is unclear.</p> <p>Methods</p> <p>A prospective, randomized, longitudinal, interventional study in a University Research Center involved a 10-week AE program in 32 women without DM and a body mass index (BMI) greater than 27 kg/m². (Cases n = 17; Controls n = 15). The primary objective was to evaluate the influence of a controlled AE program on beta-oxidation according to modifications in short, medium, and long-chain ACs. Secondary objectives were to define the behavior of amino acids, and the correlation between these modifications with metabolic and anthropometric markers.</p> <p>Results</p> <p>The proportion of dropouts was 17% and 6% in controls and cases, respectively. In cases there was a significant reduction in total carnitine (30.40 [95% CI 28.2 to 35.6]) vs. (29.4 [CI 95% 25.1 to 31.7]) <it>p =</it> 0.0008 and long-chain AC C14 (0.06 [95% CI 0.05 to 0.08]) vs. (0.05 [95% CI 0.05 to 0.09]) <it>p =</it> 0.005 and in C18 (0.31 [95% CI 0.27 to 0.45]) vs. (0.28 [95% CI 0.22 to 0.32]) <it>p =</it> 0.03. Free fatty acid levels remained without change during the study in both groups.</p> <p>Conclusion</p> <p>In conclusion, a controlled 10-week AE program improved beta-oxidation by reducing long-chain ACs. This finding highlights the importance that AE might have in avoiding or reverting lipotoxicity, and in consequence, improving insulin sensitivity and pancreatic beta cell functional reserve.</p

Mortality after surgery in Europe: a 7 day cohort study

Background: Clinical outcomes after major surgery are poorly described at the national level. Evidence of heterogeneity between hospitals and health-care systems suggests potential to improve care for patients but this potential remains unconfirmed. The European Surgical Outcomes Study was an international study designed to assess outcomes after non-cardiac surgery in Europe.Methods: We did this 7 day cohort study between April 4 and April 11, 2011. We collected data describing consecutive patients aged 16 years and older undergoing inpatient non-cardiac surgery in 498 hospitals across 28 European nations. Patients were followed up for a maximum of 60 days. The primary endpoint was in-hospital mortality. Secondary outcome measures were duration of hospital stay and admission to critical care. We used χ² and Fisher’s exact tests to compare categorical variables and the t test or the Mann-Whitney U test to compare continuous variables. Significance was set at p&lt;0·05. We constructed multilevel logistic regression models to adjust for the differences in mortality rates between countries.Findings: We included 46 539 patients, of whom 1855 (4%) died before hospital discharge. 3599 (8%) patients were admitted to critical care after surgery with a median length of stay of 1·2 days (IQR 0·9–3·6). 1358 (73%) patients who died were not admitted to critical care at any stage after surgery. Crude mortality rates varied widely between countries (from 1·2% [95% CI 0·0–3·0] for Iceland to 21·5% [16·9–26·2] for Latvia). After adjustment for confounding variables, important differences remained between countries when compared with the UK, the country with the largest dataset (OR range from 0·44 [95% CI 0·19 1·05; p=0·06] for Finland to 6·92 [2·37–20·27; p=0·0004] for Poland).Interpretation: The mortality rate for patients undergoing inpatient non-cardiac surgery was higher than anticipated. Variations in mortality between countries suggest the need for national and international strategies to improve care for this group of patients.Funding: European Society of Intensive Care Medicine, European Society of Anaesthesiology