621 research outputs found

    Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project

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    Host genetics are known to influence the gut microbiome, yet their role remains poorly understood. To robustly characterize these effects, we performed a genome-wide association study of 207 taxa and 205 pathways representing microbial composition and function in 7,738 participants of the Dutch Microbiome Project. Two robust, study-wide significant (P < 1.89 × 10-10) signals near the LCT and ABO genes were found to be associated with multiple microbial taxa and pathways and were replicated in two independent cohorts. The LCT locus associations seemed modulated by lactose intake, whereas those at ABO could be explained by participant secretor status determined by their FUT2 genotype. Twenty-two other loci showed suggestive evidence (P < 5 × 10-8) of association with microbial taxa and pathways. At a more lenient threshold, the number of loci we identified strongly correlated with trait heritability, suggesting that much larger sample sizes are needed to elucidate the remaining effects of host genetics on the gut microbiome

    Riesgo quirúrgico tras resección pulmonar anatómica en cirugía torácica. Modelo predictivo a partir de una base de datos nacional multicéntrica

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    Introduction: the aim of this study was to develop a surgical risk prediction model in patients undergoing anatomic lung resections from the registry of the Spanish Video-Assisted Thoracic Surgery Group (GEVATS). Methods: data were collected from 3,533 patients undergoing anatomic lung resection for any diagnosis between December 20, 2016 and March 20, 2018. We defined a combined outcome variable: death or Clavien Dindo grade IV complication at 90 days after surgery. Univariate and multivariate analyses were performed by logistic regression. Internal validation of the model was performed using resampling techniques. Results: the incidence of the outcome variable was 4.29% (95% CI 3.6-4.9). The variables remaining in the final logistic model were: age, sex, previous lung cancer resection, dyspnea (mMRC), right pneumonectomy, and ppo DLCO. The performance parameters of the model adjusted by resampling were: C-statistic 0.712 (95% CI 0.648-0.750), Brier score 0.042 and bootstrap shrinkage 0.854. Conclusions: the risk prediction model obtained from the GEVATS database is a simple, valid, and reliable model that is a useful tool for establishing the risk of a patient undergoing anatomic lung resection

    Grupo español de cirugía torácica asistida por videoimagen: método, auditoría y resultados iniciales de una cohorte nacional prospectiva de pacientes tratados con resecciones anatómicas del pulmón

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    Introduction: our study sought to know the current implementation of video-assisted thoracoscopic surgery (VATS) for anatomical lung resections in Spain. We present our initial results and describe the auditing systems developed by the Spanish VATS Group (GEVATS). Methods: we conducted a prospective multicentre cohort study that included patients receiving anatomical lung resections between 12/20/2016 and 03/20/2018. The main quality controls consisted of determining the recruitment rate of each centre and the accuracy of the perioperative data collected based on six key variables. The implications of a low recruitment rate were analysed for '90-day mortality' and 'Grade IIIb-V complications'. Results: the series was composed of 3533 cases (1917 VATS; 54.3%) across 33 departments. The centres' median recruitment rate was 99% (25-75th:76-100%), with an overall recruitment rate of 83% and a data accuracy of 98%. We were unable to demonstrate a significant association between the recruitment rate and the risk of morbidity/mortality, but a trend was found in the unadjusted analysis for those centres with recruitment rates lower than 80% (centres with 95-100% rates as reference): grade IIIb-V OR=0.61 (p=0.081), 90-day mortality OR=0.46 (p=0.051). Conclusions: more than half of the anatomical lung resections in Spain are performed via VATS. According to our results, the centre's recruitment rate and its potential implications due to selection bias, should deserve further attention by the main voluntary multicentre studies of our speciality. The high representativeness as well as the reliability of the GEVATS data constitute a fundamental point of departure for this nationwide cohort

    Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility

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    Estudio del diseno y factibilidad de un galpon industrial parabolico

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    296 p. (Primera Parte), 367 p. (Segunda Parte

    The Transcription Factor SCX is a Potential Serum Biomarker of Fibrotic Diseases

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    Fibrosing diseases are causes of morbidity and mortality around the world, and they are characterized by excessive extracellular matrix (ECM) accumulation. The bHLH transcription factor scleraxis (SCX) regulates the synthesis of ECM proteins in heart fibrosis. SCX expression was evaluated in lung fibroblasts and tissue derived from fibrotic disease patients and healthy controls. We also measured SCX in sera from 57 healthy controls, and 56 Idiopathic Pulmonary Fibrosis (IPF), 40 Hypersensitivity Pneumonitis (HP), and 100 Systemic Sclerosis (SSc) patients. We report high SCX expression in fibroblasts and tissue from IPF patients versus controls. High SCX-serum levels were observed in IPF (0.663 &plusmn; 0.559 ng/mL, p &lt; 0.01) and SSc (0.611 &plusmn; 0.296 ng/mL, p &lt; 0.001), versus controls (0.351 &plusmn; 0.207 ng/mL) and HP (0.323 &plusmn; 0.323 ng/mL). Serum levels of the SCX heterodimerization partner, TCF3, did not associate with fibrotic illness. IPF patients with severely affected respiratory capacities and late-stage SSc patients presenting anti-topoisomerase I antibodies and interstitial lung disease showed the highest SCX-serum levels. SCX gain-of-function induced the expression of alpha-smooth muscle actin (&alpha;-SMA/ACTA2) in fibroblasts when co-overexpressed with TCF3. As late and severe stages of the fibrotic processes correlated with high circulating SCX, we postulate it as a candidate biomarker of fibrosis and a potential therapeutic target

    Choice of DNA extraction method affects stool microbiome recovery and subsequent phenotypic association analyses

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    Abstract The lack of standardization in the methods of DNA extraction from fecal samples represents the major source of experimental variation in the microbiome research field. In this study, we aimed to compare the metagenomic profiles and microbiome–phenotype associations obtained by applying two commercially available DNA extraction kits: the AllPrep DNA/RNA Mini Kit (APK) and the QIAamp Fast DNA Stool Mini Kit (FSK). Using metagenomic sequencing data available from 745 paired fecal samples from two independent population cohorts, Lifelines-DEEP (LLD, n = 292) and the 500 Functional Genomics project (500FG, n = 453), we confirmed significant differences in DNA yield and the recovered microbial communities between protocols, with the APK method resulting in a higher DNA concentration and microbial diversity. Further, we observed a massive difference in bacterial relative abundances at species-level between the APK and the FSK protocols, with > 75% of species differentially abundant between protocols in both cohorts. Specifically, comparison with a standard mock community revealed that the APK method provided higher accuracy in the recovery of microbial relative abundances, with the absence of a bead-beating step in the FSK protocol causing an underrepresentation of gram-positive bacteria. This heterogeneity in the recovered microbial composition led to remarkable differences in the association with anthropometric and lifestyle phenotypes. The results of this study further reinforce that the choice of DNA extraction method impacts the metagenomic profile of human gut microbiota and highlight the importance of harmonizing protocols in microbiome studies

    Bizarre tail weaponry in a transitional ankylosaur from subantarctic Chile

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    Armoured dinosaurs are well known for their evolution of specialized tail weapons— paired tail spikes in stegosaurs and heavy tail clubs in advanced ankylosaurs1 . Armoured dinosaurs from southern Gondwana are rare and enigmatic, but probably include the earliest branches of Ankylosauria2–4 . Here we describe a mostly complete, semi-articulated skeleton of a small (approximately 2 m) armoured dinosaur from the late Cretaceous period of Magallanes in southernmost Chile, a region that is biogeographically related to West Antarctica5 . Stegouros elengassen gen. et sp. nov. evolved a large tail weapon unlike any dinosaur: a fat, frond-like structure formed by seven pairs of laterally projecting osteoderms encasing the distal half of the tail. Stegouros shows ankylosaurian cranial characters, but a largely ancestral postcranial skeleton, with some stegosaur-like characters. Phylogenetic analyses placed Stegouros in Ankylosauria; specifcally, it is related to Kunbarrasaurus from Australia6 and Antarctopelta from Antarctica7 , forming a clade of Gondwanan ankylosaurs that split earliest from all other ankylosaurs. The large osteoderms and specialized tail vertebrae in Antarctopelta suggest that it had a tail weapon similar to Stegouros. We propose a new clade, the Parankylosauria, to include the frst ancestor of Stegouros— but not Ankylosaurus—and all descendants of that ancestor.Fil: Soto Acuña, Sergio. Universidad de Chile; ChileFil: Vargas, Alexander O.. Universidad de Chile; ChileFil: Kaluza, Jonatan Ezequiel. Universidad de Chile; Chile. Universidad Maimónides; Argentina. Fundación de Historia Natural Félix de Azara; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Leppe, Marcelo A.. Universidad de Chile; Chile. Instituto Nacional Antártico Chileno; ChileFil: Botelho, Joao F.. Universidad de Chile; Chile. Pontificia Universidad Católica de Chile; ChileFil: Palma Liberona, José. Universidad de Chile; Chile. Pontificia Universidad Católica de Chile; ChileFil: Gutstein, Carolina Simon. Universidad de Chile; ChileFil: Fernández, Roy A.. Universidad de Chile; Chile. Universidad de Concepción; ChileFil: Ortiz, Héctor. Universidad de Chile; Chile. Universidad de Magallanes; ChileFil: Milla, Verónica. Universidad de Chile; Chile. Universidad de Concepción; ChileFil: Aravena, Bárbara. Universidad de Chile; ChileFil: Manríquez, Leslie M. E.. Universidad de Chile; Chile. Universidad de Vale do Rio dos Sinos; BrasilFil: Alarcón Muñoz, Jhonatan. Universidad de Chile; ChileFil: Pino, Juan Pablo. Universidad de Chile; ChileFil: Trevisan, Cristine. Universidad de Chile; Chile. Instituto Nacional Antártico Chileno; ChileFil: Mansilla, Héctor Sebastian. Universidad de Chile; Chile. Instituto Nacional Antártico Chileno; ChileFil: Hinojosa, Luis Felipe. Universidad de Chile; ChileFil: Muñoz Walther, Vicente. Universidad de Chile; ChileFil: Rubilar Rogers, David. Museo Nacional de Historia Natural Chile; Chile. Universidad de Chile; Chil
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