Role of the rs10401670 variant in the resistin gene on the metabolic response after weight loss secondary to a high‐fat hypocaloric diet with a Mediterranean pattern

Producción CientíficaBackground:The single nucleotide polymorphism (SNP) (rs10401670) of theRETNgene has been associated with metabolic disorder in obese subjects andhas scarcely been evaluated after dietary interventions. The present studyaimed to analyse the effects of thers10401670 RETNgene polymorphismon metabolic changes secondary to weight loss and secondary to a high‐fathypocaloric diet with a Mediterranean dietary pattern.Methods:A Caucasian population comprising 284 obese patients withoutdiabetes mellitus was analysed. Before and after 3 months of a high‐fathypocaloric diet with a Mediterranean pattern, an anthropometric evaluation,an assessment of nutritional intake and a biochemical analysis were per-formed. A statistical analysis was conducted for the combinedCTandTTas agroup and for wild‐typeCCas a second group.Results:Decreases in weight, body mass index (BMI), fat mass, systolic bloodpressure and waist circumference were similar in both genotypes groups. InTallele carriers, insulin, homeostatic model assessment for insulin resistance(HOMA‐IR), triglycerides and C‐reactive protein levels were decreased.The decrease in these parameters was statistically significant for triglycerides(−22.3 ± 9.3 mg dl–1:p= 0.03), C‐reactive protein (−2.8 ± 0.5 mg dl–1:p= 0.03), insulin (−7.4 ± 2.9 mUI L–1:p= 0.03) and HOMA‐IR (−2.4 ± 1.0:p= 0.02). Leptin levels were decreased in both genotypes groups after thehypocaloric diet, as well as the anthropometric parameters BMI, weight, waistcircumference and fat mass. Resistin and adiponectin levels remained un-changed in both groups.Conclusions:In the present study, we have detected a significant associationbetween theTallele of this SNP and a better response of insulin resistance,triglycerides and C‐reactive protein compared to nonTallele carriers afterweight loss with a high‐fat hypocaloric diet and a Mediterranean diet

Influencia de los proyectos productivos en la aplicación de los componentes electrónicos en los estudiantes del 2° año de secundaria de la I.E “Pedro E. Paulet”, Huacho, 2013

En la investigación titulada “Influencia de los Proyectos Productivos en la aplicación de los Componentes Electrónicos en los estudiantes del 2º año de secundaria de la I.E “Pedro E. Paulet”, Huacho, 2013”. El objetivo de la investigación fue determinar la influencia de los proyectos productivos en la aplicación de los componentes electrónicos en los estudiantes del 2° año de secundaria. La metodología que se utilizó para demostrar la hipótesis se elaboró en el nivel de investigación es cuasi experimental y el enfoque es cuantitativo. La población y muestra es de tipo probabilístico que constituyeron los mismos elementos de análisis que vienen a ser 30 estudiantes del 2° año de secundaria. El instrumento que se utilizó fue el cuestionario aplicado a los estudiantes. Para la validez de los instrumentos se utilizó el juicio de expertos y para la confiabilidad del instrumento se utilizó el Alpha de Crombach y el KR 20. Los resultados nos demuestran que existe influencia significativa de las variables estudiadas. Ya que por medio del análisis, comparación y descripción de las variables hemos establecido que los proyectos productivos influyen positivamente en la aplicación de los componentes electrónicos en los estudiantes 2º año de secundaria. Los datos estadísticos que sostienen esta investigación vienen de los resultados obtenidos por la aplicación de los instrumentos a los estudiantes

Effect of hypocaloric diet with a commertial formula in weight loss and quality of life in obese patients with chronic osteoarthritis

Producción CientíficaIntroducción: El objetivo de nuestro estudio fue evaluar en pacientes obesos con osteoartritis crónica el impacto sobre la calidad de vida y el control metabólico de una intervención dietética con una formula comercial hipocalórica. Material y métodos: Se evaluó una muestra de 55 pacientes obesos con osteoartritis crónica. EL estudió consistió en un programa de 12 semanas de reducción de peso en el que los paciente recibían al día dos envases de Optisource Plus®. Resultados: Se dividieron a los pacientes en dos grupos, uno que perdió menos de un 9% (grupo 1) y el grupo 2 (más de 9% de pérdida de peso). Los pacientes en el grupo 2 mostraron una mejoria en la puntuacion total del test de calidad de vida SF-36 (4,0 ± 6,1 puntos), en el campo de la función física del SF 36 (1,8 ± 3,4 puntos), el en campo del componente físico del SF 36 (0,6 ± 1,6 puntos) y en el campo de la vitalidad del SF 36 (2,7 ± 4,6 puntos). También mejoraron de manera significativa, la puntuación total del test específico de calidad de vida para osteoartritis WOMAC (-8,2 ± 15,0 puntos), el dominio funcional del test WOMAC (- 6.5+/-10.6 puntos) y el dominio de la rigidez del test WOMAC (-0,7 ± 2,1 puntos). Conclusión: El efecto sobre la calidad de vida fue superior en el grupo con porcentaje de pérdida de peso > 9% con la formula hipocalórica comercial

Relation of resistin levels with cardiovascular risk factors, insulin resistance and inflammation in naı¨ve diabetes obese patients

Producción CientíficaBackground: The aim of the present study was to explore the relationship of resistin levels with cardiovascular risk factors, insulin resistance and inflammation in naı¨ve diabetic patients. Subjects: A population of 66 naı¨ve diabetic patients with obesity was analyzed. A complete nutritional and biochemical evaluation was performed. Results: The mean age 56.9 11.6 years and the mean BMI was 37.8 6.3. Patients were divided in two groups by median resistin value (3.3 ng/ml), group I (patients with the low values, average value 2.5 0.5) and group II (patients with the high values, average value 4.8 1.8). Patients in the group I had lower waist circumference, total cholesterol, LDLcholesterol and C-reactive protein than patients in group II. Correlation analysis showed a significant correlation among resistin levels and the independent variables; BMI (r = 0.26; p < 0.05), waist circumference (r = 0.38; p < 0.05), fat mass (r = 0.28; p < 0.05), LDL-cholesterol (r = 0.3; p < 0.05), C-reactive protein (r = 0.28; p < 0.05). In the multivariate analysis, resistin concentration increase 0.024 ng/ml (CI 95%: 0.006–0.42) for each mg/dl of C-reactive protein. Conclusion: Circulating resistins are associated with C-reactive protein in an independent way in naı¨ve diabetic patients

HPLC–Tandem Mass Spectrometric Method to Characterize Resveratrol Metabolism in Humans

AbstractBackground: Nutritional biomarkers are alternatives to traditional dietary assessment tools. We sought to develop a method for nutritional analysis of resveratrol, a phenolic compound with purported health-promoting properties, and to determine all resveratrol metabolites.Methods: We obtained LDL and urine samples from 11 healthy male volunteers who had consumed 250 mL of Merlot red wine. We measured resveratrol and its metabolites with 96-well solid-phase extraction plates coupled with HPLC-tandem mass spectrometry. Hexestrol was used as the internal standard. Gradient chromatography in multiple reaction monitoring mode was performed on a Luna C18 column, maintained at 40 °C; m/z transitions were as follows: resveratrol, 227/185; resveratrol glucosides, 389/227; resveratrol glucuronides, 403/227; resveratrol sulfates, 307/227; taxifolin, 303/285; and hexestrol, 269/134.Results: Standard calibration curves were linear at 4.4–3289.5 nmol/L. Residual analyses were 100% (3.2) for trans-resveratrol and 100% (11.1) for trans-piceid. In both matrices, imprecision (CV) was &lt;10.8% at all concentrations. Detection limits for resveratrol were 0.2 nmol/L (LDL), 0.3 nmol/L (synthetic urine), and 4.0 nmol/L (blank urine). Resveratrol and metabolites were checked for stability, and no degradation was observed.Conclusions: The HPLC–tandem mass spectrometry method enabled us to identify resveratrol sulfates in human LDL and to characterize the complete profile of resveratrol metabolism in human LDL and urine. This method provides an accurate index of exposure to resveratrol and its metabolites, which can be used as nutritional biomarkers for evaluating the biological effects of moderate wine intake on human health

Obesidad en España y Castilla y León: ¿qué nos dicen los estudios?

La obesidad, es la epidemia del siglo XXI, se define como un peso corporal desproporcionado para la altura con una acumulación excesiva de tejido adiposo que se acompaña habitualmente de una inflamación sistémica crónica leve. Para clasificar a los pacientes con obesidad se utiliza el índice de Quetelet o índice de masa corporal, que se obtiene dividiendo el peso del individuo en Kg entre la talla al cuadrado en metros (kg/m2). Un índice de masa corporal por encima de 30 kg/m2 se considera como obesidad. La obesidad está asociada con el desarrollo de diabetes mellitus tipo 2, enfermedades cardiovasculares, algunos tipos de cáncer y otras condiciones patológicas crónicas. La circunferencia de la cintura también es un marcador de riesgo, en obesidad. En el estudio ENPE, se demostró una prevalencia en la población española de sobrepeso de 39,3% y de obesidad de 21,6%. La prevalencia de sobrepeso en mujeres fue de 32,1% y de obesidad de 22,8%, en varones, por otra parte, la obesidad represento un 20,5% y el sobrepeso un 46,5 %. Recientemente, en Castilla y León, la Consejería de Sanidad ha publicado los resultados de un estudio de cohortes “Estudio de Riesgo Cardiovascular en Castilla y León; la evolución de los Factores de Riesgo cardiovascular 2004-2014”. La prevalencia de obesidad (IMC ≥30) en 2004 era en nuestra Comunidad Autónoma de 22,9%. En la reevaluación de la misma cohorte de pacientes, diez años más tarde, esa proporción ha aumentado hasta el 27,6%, casi 5 puntos porcentuales. Con respecto al total de la muestra de 2014, el 31,1% tenían normopeso, el 41,3% tenían sobrepeso y el 26,1% tenían un IMC entre 30 y 40 (obesidad) y un 1,6% presentaban un IMC>40.En conclusión, la obesidad se ha convertido en una pandemia a nivel mundial, situándose España en una zona intermedia de prevalencia, así como Castilla y León. EL índice de masa corporal, así como la circunferencia de la cintura son las herramientas más utilizadas a la hora de realizar los estudios de prevalencia de obesidad.Obesity, the epidemic of the 21st century (1), is defined as a disproportionate body weight for height with an excessive accumulation of adipose tissue that is usually accompanied by a mild chronic systemic inflammation. To classify patients with obesity, the Quetelet index or body mass index is used, which is obtained by dividing the weight of the individual in Kg by the square height in meters (kg/m2). A body mass index above 30 kg/m2 is considered as obesity. Obesity is associated with the development of type 2 diabetes mellitus, cardiovascular diseases, some types of cancer and other chronic pathological conditions. Waist circumference is a risk factor in obesity, too. In the ENPE study, a prevalence in the Spanish population of overweight of 39.3% and of obesity of 21.6% was demonstrated. The prevalence of overweight in women was 32.1% and obesity 22.8%, in men; on the other hand, obesity represented 20.5% and overweight 46.5%. Recently, Castilla y León Health System has published the results of a study of cohorts “Cardiovascular Risk Study in Castilla y León; the evolution of cardiovascular risk factors 2004-2014 “. The prevalence of obesity (BMI ≥30) in 2004 was 22.9% in our Autonomous Community. In the re-evaluation of the same cohort of patients, ten years later, that proportion has increased to 27.6%, almost 5 percentage points. With respect to the total sample of 2014, 31.1% had normal weight, 41.3% were overweight and 26.1% had a BMI between 30 and 40 (obesity) and a 1, 6% had a BMI> 40 In conclusion, obesity has become a pandemic worldwide, placing Spain in an intermediate zone of prevalence as well as Castilla y León. The body mass index, as well as the circumference of the waist are the most used tools when carrying out obesity prevalence studie

Plasma-Based Bioinks for Extrusion Bioprinting of Advanced Dressings

Extrusion bioprinting based on the development of novel bioinks offers the possibility of manufacturing clinically useful tools for wound management. In this study, we show the rheological properties and printability outcomes of two advanced dressings based on platelet-rich plasma (PRP) and platelet-poor plasma (PPP) blended with alginate and loaded with dermal fibroblasts. Measurements taken at 1 h, 4 days, and 18 days showed that both the PRP- and PPP-based dressings retain plasma and platelet proteins, which led to the upregulation of angiogenic and immunomodulatory proteins by embedded fibroblasts (e.g., an up to 69-fold increase in vascular endothelial growth factor (VEGF), an up to 188-fold increase in monocyte chemotactic protein 1 (MCP-1), and an up to 456-fold increase in hepatocyte growth factor (HGF) 18 days after printing). Conditioned media harvested from both PRP and PPP constructs stimulated the proliferation of human umbilical vein endothelial cells (HUVECs), whereas only those from PRP dressings stimulated HUVEC migration, which correlated with the VEGF/MCP-1 and VEGF/HGF ratios. Similarly, the advanced dressings increased the level of interleukin-8 and led to a four-fold change in the level of extracellular matrix protein 1. These findings suggest that careful selection of plasma formulations to fabricate wound dressings can enable regulation of the molecular composition of the microenvironment, as well as paracrine interactions, thereby improving the clinical potential of dressings and providing the possibility to tailor each composition to specific wound types and healing stages.This work was fully supported by a collaborative fundamental research grant from the Basque Government Elkartek program under grant nº. B4H KK-2019-0006-BC

An Epilepsy-Causing Mutation Leads to Co-Translational Misfolding of the Kv7.2 Channel

BACKGROUND: The amino acid sequence of proteins generally carries all the necessary information for acquisition of native conformations, but the vectorial nature of translation can additionally determine the folding outcome. Such consideration is particularly relevant in human diseases associated to inherited mutations leading to structural instability, aggregation, and degradation. Mutations in the KCNQ2 gene associated with human epilepsy have been suggested to cause misfolding of the encoded Kv7.2 channel. Although the effect on folding of mutations in some domains has been studied, little is known of the way pathogenic variants located in the calcium responsive domain (CRD) affect folding. Here, we explore how a Kv7.2 mutation (W344R) located in helix A of the CRD and associated with hereditary epilepsy interferes with channel function. RESULTS: We report that the epilepsy W344R mutation within the IQ motif of CRD decreases channel function, but contrary to other mutations at this site, it does not impair the interaction with Calmodulin (CaM) in vitro, as monitored by multiple in vitro binding assays. We find negligible impact of the mutation on the structure of the complex by molecular dynamic computations. In silico studies revealed two orientations of the side chain, which are differentially populated by WT and W344R variants. Binding to CaM is impaired when the mutated protein is produced in cellulo but not in vitro, suggesting that this mutation impedes proper folding during translation within the cell by forcing the nascent chain to follow a folding route that leads to a non-native configuration, and thereby generating non-functional ion channels that fail to traffic to proper neuronal compartments. CONCLUSIONS: Our data suggest that the key pathogenic mechanism of Kv7.2 W344R mutation involves the failure to adopt a configuration that can be recognized by CaM in vivo but not in vitroThe Government of the Autonomous Community of the Basque Country (IT1165-19 and KK-2020/00110) and the Spanish Ministry of Science and Innovation (RTI2018-097839-B-100 to A.V. and FIS2016-76617-P to A.B.) and FEDER funds and the US National Institute of Neurological Disorders (NINDS) and Stroke Research Project Grant (R01NS083402 to H.J.C.) provided financial support for this work. E.N. and A.M-M. are supported by predoctoral contracts from the Basque Government administered by University of the Basque Country. C.M. was supported by the Basque Government through a Basque Excellence Research Centre (BERC) grant administered by Fundación Biofisika Bizkaia (FBB). J.U. was partially supported by BERC funds. O.R.B. was supported by the Basque Government through a BERC grant administered by Donostia International Physics Center. J.Z. and H.J.C. was supported by the NINDS Research Project Grant #R01NS083402 (PI: H.J.C.)

OPTIMIZATION OF TISSUE SAMPLES FOR THE DEVELOPMENT AND VALIDATION OF DISEASE BIOMARKERS: THE OPTIMARK PROJECT

Europe Biobank Week, Sept 13-16, 2016. Vienna, AustriaS