Polymorphic Inversions Underlie the Shared Genetic Susceptibility of Obesity-Related Diseases

The burden of several common diseases including obesity, diabetes, hypertension, asthma, and depression is increasing in most world populations. However, the mechanisms underlying the numerous epidemiological and genetic correlations among these disorders remain largely unknown. We investigated whether common polymorphic inversions underlie the shared genetic influence of these disorders. We performed an inversion association analysis including 21 inversions and 25 obesity-related traits on a total of 408,898 Europeans and validated the results in 67,299 independent individuals. Seven inversions were associated with multiple diseases while inversions at 8p23.1, 16p11.2, and 11q13.2 were strongly associated with the co-occurrence of obesity with other common diseases. Transcriptome analysis across numerous tissues revealed strong candidate genes for obesity-related traits. Analyses in human pancreatic islets indicated the potential mechanism of inversions in the susceptibility of diabetes by disrupting the cis-regulatory effect of SNPs from their target genes. Our data underscore the role of inversions as major genetic contributors to the joint susceptibility to common complex diseases.This research has received funding from Ministerio de Ciencia, Innovación y Universidades (MICIU), Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional, UE (RTI2018-100789-B-I00) also through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S); and the Catalan Government through the CERCA Program and projects SGR2017/801 and #016FI_B 00272 to CR-A. JG is funded by the European Commission (H2020-ERC-2014-CoG-647900) and the MINECO/AEI/FEDER, EU (BFU2017-82937-P). LAPJ lab was funded by the Spanish Ministry of Science and Innovation (ISCIII-FEDER P13/02481), the Catalan Department of Economy and Knowledge (SGR2014/1468, SGR2017/1974 and ICREA Acadèmia), and also acknowledges support from the Spanish Ministry of Economy and Competiveness “Programa de Excelencia María de Maeztu” (MDM-2014-0370). This research was conducted using the UK Biobank Resource under Application Number 43983. The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS.Peer ReviewedPostprint (author's final draft

Estudio longitudinal de lesiones deportivas en practicantes de gimnasia aeróbica de competición

Introduction: Aerobic gymnastics, since its membership in the International Gymnastics Federation, has undergone changes in its regulations. Objective: To analyze the injuries found in Spanish aerobic gymnastics athletes during different editions of the Code of Points. Methods: A descriptive, longitudinal and compara-tive study was carried out on the epidemiology of injuries in aerobic gymnastics published during different editions of the Code of Points. Results: It highlights that the number of injuries decreased from 156 to 38 last year. This decline has been related to the restriction on the number of difficulties in the exercise and the number of elements to be performed on the floor. However, they have increased the number and value of the difficulties. Conclusions: Therefore, it is concluded that the changes made in the regulations are intended to safeguard the health of athletes and ensure that competition develops at its best artistic and technical aspect.Introdução: A ginástica aeróbica, desde sua adesão à Federação Internacional de Ginástica, passou por mudanças em seus regulamentos. Objetivo: Analisar as lesões encontradas nos atletas espanhóis de ginástica aeróbica durante as diferentes edições do Código de Pontos. Métodos: Realizou-se um estudo descritivo, longitudinal e comparativo sobre a epidemiologia de lesões na ginástica aeróbica publicado durante as diferentes edições do Código de Pontos. Resultados Salienta-se que o número de lesões diminuiu de 156 para 38 no ano passado. Este declínio tem sido relacionado com a limitação do número de dificuldades no exercício e o número de elementos a serem feitos no solo. No entanto, eles aumentaram o número e valor das dificuldades. Conclusões: Portanto, concluiu-se que as modificações feitas nos regulamentos destinam-se a salvaguardar a saúde dos atletas e garantir que a competição se desenvolva no seu melhor aspecto artístico e técnico.Introducción: La gimnasia aeróbica desde su pertenencia a la Federación Internacional de Gimnasia ha sufrido cam-bios en su reglamentación. Objetivo: Analizar las lesiones que los deportistas españoles de gimnasia aeróbica presentaron durante las diferentes ediciones del Código de Puntuación. Métodos: Se ha realizado un estudio descriptivo, longitudinal y comparativo sobre la epidemiología de las lesiones en la gimnasia aeróbica publicado durante las diferentes ediciones del Código de Puntuación. Resultados: El estudio destaca la disminución del número de lesiones, de 156 a 38 en el último año. Esta disminución ha tenido relación con la restricción del número de dificultades en el ejercicio y la cantidad de elementos a realizar en el suelo. Sin embargo, han aumentado el número y el valor de las dificultades. Conclusiones: Por tanto, han concluido que las modificaciones que se realizan en la reglamentación tienen como objetivo velar por la salud de los deportistas y garantizar que la competición se desarrolle en su máximo esplendor artístico y técnico

TIGER : The gene expression regulatory variation landscape of human pancreatic islets

Genome-wide association studies (GWASs) identified hundreds of signals associated with type 2 diabetes (T2D). To gain insight into their underlying molecular mechanisms, we have created the translational human pancreatic islet genotype tissue-expression resource (TIGER), aggregating >500 human islet genomic datasets from five cohorts in the Horizon 2020 consortium T2DSystems. We impute genotypes using four reference panels and meta-analyze cohorts to improve the coverage of expression quantitative trait loci (eQTL) and develop a method to combine allele-specific expression across samples (cASE). We identify >1 million islet eQTLs, 53 of which colocalize with T2D signals. Among them, a low-frequency allele that reduces T2D risk by half increases CCND2 expression. We identify eight cASE colocalizations, among which we found a T2D-associated SLC30A8 variant. We make all data available through the TIGER portal (http://tiger.bsc.es), which represents a comprehensive human islet genomic data resource to elucidate how genetic variation affects islet function and translates into therapeutic insight and precision medicine for T2D.Peer reviewe

Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes.

The reanalysis of existing GWAS data represents a powerful and cost-effective opportunity to gain insights into the genetics of complex diseases. By reanalyzing publicly available type 2 diabetes (T2D) genome-wide association studies (GWAS) data for 70,127 subjects, we identify seven novel associated regions, five driven by common variants (LYPLAL1, NEUROG3, CAMKK2, ABO, and GIP genes), one by a low-frequency (EHMT2), and one driven by a rare variant in chromosome Xq23, rs146662057, associated with a twofold increased risk for T2D in males. rs146662057 is located within an active enhancer associated with the expression of Angiotensin II Receptor type 2 gene (AGTR2), a modulator of insulin sensitivity, and exhibits allelic specific activity in muscle cells. Beyond providing insights into the genetics and pathophysiology of T2D, these results also underscore the value of reanalyzing publicly available data using novel genetic resources and analytical approaches

Azotobacter genomes: the genome of Azotobacter chroococcum NCIMB 8003 (ATCC 4412)

The genome of the soil-dwelling heterotrophic N2-fixing Gram-negative bacterium Azotobacter chroococcum NCIMB 8003 (ATCC 4412) (Ac-8003) has been determined. It consists of 7 circular replicons totalling 5,192,291 bp comprising a circular chromosome of 4,591,803 bp and six plasmids pAcX50a, b, c, d, e, f of 10,435 bp, 13,852, 62,783, 69,713, 132,724, and 311,724 bp respectively. The chromosome has a G+C content of 66.27% and the six plasmids have G+C contents of 58.1, 55.3, 56.7, 59.2, 61.9, and 62.6% respectively. The methylome has also been determined and 5 methylation motifs have been identified. The genome also contains a very high number of transposase/inactivated transposase genes from at least 12 of the 17 recognised insertion sequence families. The Ac-8003 genome has been compared with that of Azotobacter vinelandii ATCC BAA-1303 (Av-DJ), a derivative of strain O, the only other member of the Azotobacteraceae determined so far which has a single chromosome of 5,365,318 bp and no plasmids. The chromosomes show significant stretches of synteny throughout but also reveal a history of many deletion/insertion events. The Ac-8003 genome encodes 4628 predicted protein-encoding genes of which 568 (12.2%) are plasmid borne. 3048 (65%) of these show > 85% identity to the 5050 protein-encoding genes identified in Av-DJ, and of these 99 are plasmid-borne. The core biosynthetic and metabolic pathways and macromolecular architectures and machineries of these organisms appear largely conserved including genes for CO-dehydrogenase, formate dehydrogenase and a soluble NiFe-hydrogenase. The genetic bases for many of the detailed phenotypic differences reported for these organisms have also been identified. Also many other potential phenotypic differences have been uncovered. Properties endowed by the plasmids are described including the presence of an entire aerobic corrin synthesis pathway in pAcX50f and the presence of genes for retro-conjugation in pAcX50c. All these findings are related to the potentially different environmental niches from which these organisms were isolated and to emerging theories about how microbes contribute to their communities

Implementation of the evidence for the improvement of nursing care to the critical patient's family: a participatory action research

Background: There are many descriptive studies regarding the needs of the family, as well as those regarding nursing care aimed directly at family members. However, there is no widespread application of such evidence in clinical practice. There has also been no analysis made of the evolution of patterns of knowing during the act of improving clinical practice. Therefore, the purpose of the study is to understand the change process aimed at improving care to critical patient's families, and to explore the evolution of patterns of knowing that nurses use in this process. Methods: Qualitative study with a Participatory Action Research method, in accordance with the Kemmis and McTaggart model. In this model, nurses can observe their practice, reflect upon it and compare it with scientific evidence, as well as define, deploy and evaluate improvement strategies adapted to the context. Simultaneously, the process of empowerment derived from the Participatory Action Research allows for the identification of patterns of knowing and their development over time. The research will take place in the Intensive Care Units of a tertiary hospital. The participants will be nurses who are part of the regular workforce of these units, with more than five years of experience in critical patients, and who are motivated to consider and critique their practice. Data collection will take place through participant observation, multi-level discussion group meetings and documentary analysis. A content analysis will be carried out, following a process of codification and categorisation, with the help of Nvivo10. The approval date and the beginning of the funding were December 2012 and 2013, respectively. Discussion: The definition, introduction and evaluation of care strategies for family members will allow for their real and immediate implementation in practice. The study of the patterns of knowing in the Participatory Action Research will be part of the theoretical and practical feedback process of a professional discipline. Also, the identification of the construction and evolution of knowledge will provide decision elements to managers and academics when choosing strategies for increased quality

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

A first update on mapping the human genetic architecture of COVID-19

peer reviewe