Búsqueda de perfiles genéticos de susceptibilidad heredada a obesidad severa

Obesity is considered today as a global epidemic of a chronic disease that generates an abnormal or excessive accumulation of fat, which in a significant percentage of patients appears from very early ages and a large part of life is maintained. In addition to the direct and indirect costs that it causes, it is a serious prejudice to the quality of life and health of the individuals affected. In general, it is widely accepted that both genes and the environment participate in the constitution and maintenance of body weight. It has been estimated that hereditary factors participate between 40 and 70% of individual susceptibility to the onset of obesity.However, our knowledge about the genetic bases associated with the development of a serious and intractable overweight, remains negligible. Our Group of the Genomics Laboratory of the Research Foundation of the General University Hospital of Valencia, has the opportunity to present our main line of research to all the academics, collaborators and assistants of the Royal Academy of Medicine of Valladolid. The possibility of presenting and receiving the opinion of such a multidisciplinary team of professionals with great experience in the health field, has allowed us to contrast the strategy we have designed to direct our activity in the study and identification of the genetic predisposition to obesity. We have maintained for a decade, the firm objective of demonstrating and characterizing the existence of inherited and transmissible profiles that predispose from early childhood to develop a physical aspect whose main characteristic is serious overweight.La obesidad es considerada en la actualidad como una epidemia mundial de una enfermedad crónica que genera una acumulación anormal o excesiva de grasa, que en un porcentaje importante de los pacientes aparece desde edades muy tempranas y se mantiene gran parte de la vida. Además de los costes directos e indirectos que ocasiona, supone un gravísimo perjuicio para la calidad de vida y la salud de los individuos afectados. De manera general, se admite ampliamente que tanto los genes como el medio ambiente participan en la constitución y el mantenimiento del peso corporal. Se ha estimado que los factores hereditarios participan entre el 40 y el 70% de la susceptibilidad individual para la aparición de la obesidad. Sin embargo, nuestro conocimiento acerca de las bases genéticas asociadas al desarrollo de un sobrepeso grave e intratable, sigue siendo ínfimo.Nuestro Grupo del Laboratorio de Genómica de la Fundación Investigación Hospital General Universitario de Valencia, tiene la oportunidad de presentar nuestra principal línea de investigación al conjunto de los académicos, colaboradores y asistentes de la Real Academia de Medicina de Valladolid. La posibilidad de exponer y recibir la opinión de un conjunto tan multidisciplinar de profesionales de gran experiencia en el ámbito sanitario, nos ha permitido contrastar la estrategia que hemos diseñado para dirigir nuestra actividad en el estudio e identificación de la predisposición genética a la obesidad. Mantenemos desde hace ya una década, el objetivo firme de demostrar y caracterizar la existencia de perfiles heredados y transmisibles que predisponen desde la primera infancia a desarrollar un aspecto físico cuya principal característica es el sobrepeso grave

Loss of Arabidopsis β-COP Function Affects Golgi Structure, Plant Growth and Tolerance to Salt Stress

The early secretory pathway involves bidirectional transport between the endoplasmic reticulum (ER) and the Golgi apparatus and is mediated by coat protein complex I (COPI)-coated and coat protein complex II (COPII)-coated vesicles. COPII vesicles are involved in ER to Golgi transport meanwhile COPI vesicles mediate intra-Golgi transport and retrograde transport from the Golgi apparatus to the ER. The key component of COPI vesicles is the coatomer complex, that is composed of seven subunits (α/β/β'/γ/δ/ε/ζ). In Arabidopsis two genes coding for the β-COP subunit have been identified, which are the result of recent tandem duplication. Here we have used a loss-of-function approach to study the function of β-COP. The results we have obtained suggest that β-COP is required for plant growth and salt tolerance. In addition, β-COP function seems to be required for maintaining the structure of the Golgi apparatus

Protein Identification and Haplotype Description of Homozygote Mutation Causing Congenital Plasminogen Deficiency

Severe type I Plasminogen (PLG) deficiency was clinically diagnosed after hyaline-positive periodic acid Schiff material was detected in the histologic study of superior tarsal conjunctiva and vulvar pseudomembrane of the patient. Direct immunofluorescence also confirmed multiple deposits of fibrinogen in the dermis. Plasma plasminogen activity was calculated in a <5% value (reference values, 75% to 150%) and sequencing of the PLG gene evidenced the homozygous mutation in c.2377T/A (p.Tyr793Asn), confirming the molecular diagnosis of congenital deficiency of plasminogen type 1. Genotype-Phenotype correlation among family members evidenced the recessive hereditary pattern of clinical manifestations of chronic inflammatory disease of the mucous membranes due to PLG deficiency, but co-dominance effect to present a decreased plasma plasminogen activity (46%) among heterozygous asymptomatic individuals. SNPs/CNVs whole genome array hybridization analysis in the patient, detected long Loss of Heterozygosity regions (LOH) and demonstrated the consanguinity in the family. Proteomic analysis identified impaired secretion of mutant PLG tissue specific proteins, as definitive molecular etiopathogenesis of the type I PLG deficiency in the patient

Búsqueda de perfiles genéticos de susceptibilidad heredada a obesidad severa

Obesity is considered today as a global epidemic of a chronic disease that generates an abnormal or excessive accumulation of fat, which in a significant percentage of patients appears from very early ages and a large part of life is maintained. In addition to the direct and indirect costs that it causes, it is a serious prejudice to the quality of life and health of the individuals affected. In general, it is widely accepted that both genes and the environment participate in the constitution and maintenance of body weight. It has been estimated that hereditary factors participate between 40 and 70% of individual susceptibility to the onset of obesity. However, our knowledge about the genetic bases associated with the development of a serious and intractable overweight, remains negligible. Our Group of the Genomics Laboratory of the Research Foundation of the General University Hospital of Valencia, has the opportunity to present our main line of research to all the academics, collaborators and assistants of the Royal Academy of Medicine of Valladolid. The possibility of presenting and receiving the opinion of such a multidisciplinary team of professionals with great experience in the health field, has allowed us to contrast the strategy we have designed to direct our activity in the study and identification of the genetic predisposition to obesity. We have maintained for a decade, the firm objective of demonstrating and characterizing the existence of inherited and transmissible profiles that predispose from early childhood to develop a physical aspect whose main characteristic is serious overweight.La obesidad es considerada en la actualidad como una epidemia mundial de una enfermedad crónica que genera una acumulación anormal o excesiva de grasa, que en un porcentaje importante de los pacientes aparece desde edades muy tempranas y se mantiene gran parte de la vida. Además de los costes directos e indirectos que ocasiona, supone un gravísimo perjuicio para la calidad de vida y la salud de los individuos afectados. De manera general, se admite ampliamente que tanto los genes como el medio ambiente participan en la constitución y el mantenimiento del peso corporal. Se ha estimado que los factores hereditarios participan entre el 40 y el 70% de la susceptibilidad individual para la aparición de la obesidad. Sin embargo, nuestro conocimiento acerca de las bases genéticas asociadas al desarrollo de un sobrepeso grave e intratable, sigue siendo ínfimo. Nuestro Grupo del Laboratorio de Genómica de la Fundación Investigación Hospital General Universitario de Valencia, tiene la oportunidad de presentar nuestra principal línea de investigación al conjunto de los académicos, colaboradores y asistentes de la Real Academia de Medicina de Valladolid. La posibilidad de exponer y recibir la opinión de un conjunto tan multidisciplinar de profesionales de gran experiencia en el ámbito sanitario, nos ha permitido contrastar la estrategia que hemos diseñado para dirigir nuestra actividad en el estudio e identificación de la predisposición genética a la obesidad. Mantenemos desde hace ya una década, el objetivo firme de demostrar y caracterizar la existencia de perfiles heredados y transmisibles que predisponen desde la primera infancia a desarrollar un aspecto físico cuya principal característica es el sobrepeso grave

Effects of pre-operative isolation on postoperative pulmonary complications after elective surgery: an international prospective cohort study an international prospective cohort study

We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05–1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4–7 days or ≥ 8 days of 1.25 (1.04–1.48), p = 0.015 and 1.31 (1.11–1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care. We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05–1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4–7 days or ≥ 8 days of 1.25 (1.04–1.48), p = 0.015 and 1.31 (1.11–1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care