Quantification of mitochondrial DNA in human whole blood using real- time quantitative PCR

Las variaciones en el contenido de mtDNA se han asociado con diferentes situaciones patológicas. Su determinación en sangre es un parámetro de interés pero se ve afectado por numerosas variables. El objetivo del presente proyecto es analizar la influencia de estas variables de cara a establecer un protocolo eficiente y reproducible. La PCR a tiempo real es una técnica que se está aplicando ampliamente en las ciencias biomédicas para la cuantificación de DNA tanto mitocondrial como genómico. En este estudio trabajamos con sangre total para cuantificar el DNA mitocondrial, calculado como el ratio DNA mitocondrial/DNA nuclear. Hemos iniciado el estudio de diferentes variables que pueden afectar a dicha cuantificación. Así, se ha comprobado que la concentración de plaquetas, orgánulos que contienen DNA mitocondrial pero no DNA nuclear, afecta de forma significativa en la determinación final. De igual modo hemos estudiado la influencia que produce en la cuantificación el método de extracción utilizado para obtener el DNA y la variabilidad inter-día e intra-día en el método de extracción. Se han encontrado diferencias significativas en todas estas variables. Para realizar estos análisis hemos creado un plásmido fruto de la fusión de nuestros genes de estudio (mitocondrial y nuclear) con el fin de realizar una calibración de las medidas mediante una recta de calibrado realizada con diluciones seriadas de este estándar. También hemos estudiado la influencia de la conformación del material genético en la eficacia de la reacción de PCR y se ha visto que, puesto que al digerir el DNA mitocondrial con una enzima la cuantificación de DNA mitocondrial se ve aumentada. En la continuación del proyecto queremos seguir clarificando las fuentes de variabilidad que afectan a la técnica de PCR a tiempo real en la cuantificación de DNA mitocondrial

Current causes of death in familial hypercholesterolemia

Background Familial hypercholesterolemia (FH) is a codominant autosomal disease characterized by high low-density lipoprotein cholesterol (LDLc) and a high risk of premature cardiovascular disease (CVD). The molecular bases have been well defined, and effective lipid lowering is possible. This analysis aimed to study the current major causes of death of genetically defined heterozygous familial hypercholesterolemia (heFH). Methods A case‒control study was designed to analyse life-long mortality in a group of heFH and control families. Data from first-degree family members of cases and controls (nonconsanguineous cohabitants), including deceased relatives, were collected from a questionnaire and review of medical records. Mortality was compared among heFH patients, nonheFH patients, and nonconsanguineous family members. Results A total of 813 family members were analysed, 26.4% of whom were deceased. Among the deceased, the mean age of death was 69.3 years in heFH individuals, 73.5 years in nonheFH individuals, and 73.2 years in nonconsanguineous individuals, without significant differences. CVD was the cause of death in 59.7% of heFH individuals, 37.7% of nonheFH individuals, and 37.4% of nonconsanguineous individuals (P = 0.012). These differences were greater after restricting the analyses to parents. The hazard ratio of dying from CVD was 2.85 times higher (95% CI, (1.73–4.69) in heFH individuals than in individuals in the other two groups (non-FH and nonconsanguineous), who did not differ in their risk. Conclusions CVD mortality in heFH individuals is lower and occurs later than that described in the last century but is still higher than that in non-FH individuals. This improved prognosis of CVD risk is not associated with changes in non-CVD mortality

Exposure to dietary polychlorinated biphenyls and dioxins, and its relationship with subclinical coronary atherosclerosis: The Aragon workers' health study

Background: Experimental evidence has revealed that exposure to polychlorinated biphenyls (PCBs) and dioxins directly impairs endothelial function and induces atherosclerosis progression. In the general population, despite a small number of recent studies finding a link between PCBs, and stroke and myocardial infraction, the association with early coronary atherosclerosis has not been examined yet. Objective: To examine whether dietary exposure to PCBs and dioxins is associated with subclinical coronary atherosclerosis in a middle-aged men. Design: Cross-sectional analysis comprising 1844 men in their 50 s and free of cardiovascular disease, who participated in the Aragon Workers' Health Study (AWHS). Individual dietary exposures to PCBs and dioxins were estimated by the contaminant’s concentration in food coupled with the corresponding consumption and then participants were classified into quartiles of consumption. Coronary artery calcium score (CACS) was assessed by computerized tomography. We conducted ordered logistic regressions to estimate the odds ratio (OR) and 95% confidence intervals (CIs) for progression to the categories of more coronary artery calcium, adjusting for potential confounders. Results: Among the participants, coronary calcium was not shown in 60.1% (n=1108), 29.8% had a CACS > 0 and<100 (n=550), and the remaining 10.1% (n=186) had a CACS≥100. Compared with those in the first quartile of PCBs exposure, those in the fourth one had an increased odds for having coronary calcium (OR 2.02, 95% CI [1.18, 3.47], p trend 0.019) and for having progressed to categories of more intense calcification (OR 2.03, 95% CI [1.21, 3.40], p trend 0.012). However, no association was found between dietary dioxins exposure and prevalent coronary artery calcium. Conclusions: In this general male population, dietary exposure to PCBs, but not to dioxins, was associated with a higher prevalence of coronary calcium and to more intense subclinical coronary atherosclerosis. PCBs exposure seems to increase the risk of coronary disease in men from the very early stagesThis work was supported by the Instituto Aragonés de Ciencias de la Salud (I+CS) of the regional Government of Aragón, the National Center for Cardiovascular Research (CNIC) of the Instituto de Salud Carlos III, and Opel Spain. This study was also partially supported by grants: PI17/1709 (State Secretary of R+D and FEDER/FSE), and Excellence Integrated Projects in Health Research Institutes PIE16/ 00022 (State Secretary of R+D and FEDER/FSE), the ATHLOS project (EU H2020-Project ID: 635316), CIBERCV and CIBERESP from the Instituto de Salud Carlos III. Madrid, Spain. We also acknowledge the Juan de la Cierva-formación (Spanish State Research Agency) for funding grant to Carolina Donat-Varga

REGULACIÓN TIROIDEA Y EMBARAZO

Las hormonas tiroideas cambian en la madre durante el embarazo , y la patología tiroidea preexistente y el estado tiroidea fisiológico durante el embarazo puede influir en los resultados de la gestación. Existe una relación en la población general entre la regulación tiroidea y la diabetes y en un estudio preliminar observamos que esta disminuye en embarazadas.<br /

Phthalate exposure and the metabolic syndrome: A systematic review and meta-analysis

Phthalates are chemicals widely used in plastic-based consumer products, and human exposure is universal. They are classified as endocrine disruptors, and specific phthalate metabolites have been associated with an increased risk of cardiometabolic diseases. The aim of this study was to assess the association between phthalate exposure and the metabolic syndrome in the general population. A comprehensive literature search was performed in four databases (Web of Science, Medline, PubMed, and Scopus). We included all the observational studies that evaluate the association between phthalate metabolites and the metabolic syndrome available until January 31st, 2023. Pooled Odds Ratios (OR) and their 95% confidence intervals were calculated by using the inversevariance weighted method. Nine cross-sectional studies and 25,365 participants aged from 12 to 80 were included. Comparing extreme categories of phthalate exposure, the pooled ORs for the metabolic syndrome were: 1.08 (95% CI, 1.02–1.16, I 2 = 28%) for low molecular weight phthalates, and 1.11 (95% CI, 1.07–1.16, I 2 = 7%) for high molecular weight phthalates. For individual phthalate metabolites, the pooled ORs that achieved statistical significance were: 1.13 (95% CI, 1.00–1.27, I 2 = 24%) for MiBP; 1.89 (95% CI, 1.17–3.07, I 2 = 15%) for MMP in men; 1.12 (95% CI, 1.00–1.25, I 2 = 22%) for MCOP; 1.09 (95% CI, 0.99–1.20, I 2 = 0%) for MCPP; 1.16 (95% CI, 1.05–1.28, I 2 = 6%) for MBzP; and 1.16 (95% CI, 1.09–1.24, I 2 = 14%) for DEHP (including ΣDEHP and its metabolites). In conclusion, both low molecular weight and high molecular weight phthalates were associated with an 8 and 11% higher prevalence of the MetS, respectively. The exposure to six specific phthalate metabolites was associated with a higher prevalence of the MetSData collection was funded by the following grants: FIS PI17/1709, PI20/144 (State Secretary of R + D and FEDER/FSE), and the CIBERESP, Instituto de Salud Carlos III. Madrid, Spain. MM has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement [(No 801342 (Tecniospring INDUSTRY)] and the Government of Catalonia’s Agency for Business Competitiveness (ACCIO) ´ (TECSPR19-1-0022

Association of beverage consumption with subclinical atherosclerosis in a Spanish working population

Beverages play a substantial role meeting water, calorie, and nutrient requirements; however, they are presented as being major contributors to the current obesity epidemic. Although, the relationship between beverage consumption and metabolic risk factors for cardiovascular disease (CVD) in adults has been frequently studied, its association with subclinical atherosclerosis is of increased interest. We studied the association of beverage consumption with the presence of peripheral subclinical atherosclerosis among Spanish workers. We performed a cross-sectional study of 2089 middle-aged males, with a mean age of 50.9 (SD 3.9), and without CVD, carried out in the Aragon Workers’ Health Study (AWHS). A food frequency questionnaire was used to measure beverage consumption of low-fat milk, coffee and tea (unsweetened), whole-fat milk, sugar-sweetened beverages, bottled fruit juice, artificially-sweetened beverages and 100% fruit juice. Atherosclerotic plaques were measured by ultrasound (in carotid arteries, and in femoral arteries). Atherosclerotic plaque was defined as a focal structure protruding ≥ 0.5 mm into the lumen, or reaching a thickness ≥ 50% of the surrounding intima-media thickness. As statistical analysis, we use logistic regression models, simultaneously adjusted for all beverage groups. As results, unsweetened coffee was the beverage most associated with peripheral subclinical atherosclerosis with an odds ratio (OR) of 1.25 (1.10–1.41), and 1.23 (1.09–1.40) 100g/day] for carotid, and femoral territories respectively. Moreover, subclinical atherosclerosis was positively associated with whole-fat milk [OR 1.10 (1.02–1.18) 100 g/day] in the femoral territory. The association was protective for low-fat milk in the carotid territory [OR 0.93 (0.88–0.99) 100g/day]. There was also a protective association with bottled fruit juices in the femoral territory [0.84 (0.74–0.94) 100g/day]. Our results suggest a detrimental association with the consumption of coffee, as well as with whole-fat milk and the presence of subclinical atherosclerosis. Therefore, an element of prudence excluding water and low-fat milk, must be applied when recommending beverage consumption

Cataract Surgery in Elderly Subjects with Heterozygous Familial Hypercholesterolemia in Prolonged Treatment with Statins

Background: Cataracts are the main cause of blindness and represent one fifth of visual problems worldwide. It is still unknown whether prolonged statin treatment favors the development of cataracts. We aimed to ascertain the prevalence of cataract surgery in elderly subjects with genetically diagnosed heterozygous familial hypercholesterolemia (HeFH) receiving statin treatment for ≥5 years, and compare this with controls. Methods: This is an observational, multicenter, case–control study from five lipid clinics in Spain. We collected data with the following inclusion criteria: age ≥65 years, LDL cholesterol levels ≥220 mg/dL without lipid-lowering drugs, a pathogenic mutation in a candidate gene for HeFH (LDLR, APOB, or PCSK9) and statin treatment for ≥5 years. Controls were selected from relatives of HeFH patients without hypercholesterolemia. Linear and logistic regressions based on generalized linear models and generalized estimating equations (GEE) were used. Cataract surgery was used as a proxy for cataract development. Results: We analyzed 205 subjects, 112 HeFH, and 93 controls, with a mean age of 71.8 (6.5) and 70.0 (7.3) years, respectively. HeFH subjects presented no difference in clinical characteristics, including smoking, hypertension, and type 2 diabetes mellitus, compared with controls. The mean duration of lipid-lowering treatment in HeFH was 22.5 (8.7) years. Cataract surgery prevalence was not significantly different between cases and controls. The presence of cataracts was associated neither with LDLc nor with the length of the statin therapy. Conclusion: In the present study, HeFH was not a risk factor for cataract surgery and prolonged statin treatment did not favor it either. These findings suggest that statin treatment is not related with cataracts

High consumption of ultra-processed food may double the risk of subclinical coronary atherosclerosis: The Aragon Workers' Health Study (AWHS)

Background: Ultra-processed food (UPF) consumption, which is increasing worldwide, has recently been associated with an increased risk of death and cardiovascular disease. We aimed to assess whether consumption of UPF is directly associated with subclinical coronary atherosclerosis in middle-aged men. Methods: A computed tomography scan was performed on 1876 men from the Aragon Workers' Health Study, recruited from January 2011 to December 2014, to assess coronary calcium. All participants were free of coronary heart disease. Dietary intake was collected by a validated 136-item semi-quantitative food frequency questionnaire. UPF was defined according to the NOVA classification. Associations between consumption of total energy-adjusted UPF and Coronary Calcium Agatston Score (CACS) - categorized into CACS of 0, > 0 and 0 and < 100). The fully adjusted ORs (95% CI) of having a CACS ≥ 100 across quartiles of energy-adjusted UPF consumption (approximately 100 g/day in the lowest quartile (ref.) and 500 g/day in the highest) were 1.00 (ref.), 1.50 (0.93, 2.42), 1.56 (0.96, 2.52), and 2.00 (1.26, 3.16), p trend.005. Conclusion: In this middle-aged worker's sample, approximately 500 g/day of UPF consumption was associated with a 2-fold greater prevalence of subclinical coronary atherosclerosis than consuming only 100 g/day, independently of total energy intake and other well-established cardiovascular risk factorsAWHS was funded through a collaboration agreement between the Aragonese Institute of Health Sciences (I+CS) of the Regional Government of Aragon, the National Cardiovascular Research Centre (CNIC) of the Carlos III Health Institute, and Opel Spain. This study was also partially supported by grants: PI17/1709 (Secretary of State for R&D and ERDF/ESF), and Integrated Projects of Excellence in Health Research Institutes PIE16/00022 (Secretary of State for R&D and ERDF/ESF), the ATHLOS Project (EU H2020-ID project: 635316), CIBERCV and CIBERESP of the Carlos III Health Institute, Madrid, Spai

Hipercolesterolemia con elevación simultánea de LDL-c y HDL-c: ¿Un nuevo fenotipo?

Introducción. Algunos pacientes con hipercolesterolemia presentan elevación simultánea del colesterol unido a LDL (LDL-c) y del colesterol unido a HDL (HDL-c). No se dispone de trabajos que hayan estudiado esta alteración en grandes poblaciones. Objetivos. Estudiar si existe un subgrupo de pacientes con LDL-c y HDL-c simultáneamente elevados con unas características clínicas propias, que configurarían una nueva entidad dentro de las dislipemias de origen desconocido.Material y métodos. Se diseñó un estudio transversal en el que se incluyó a todos los pacientes de la consulta de dislipemias primarias del Hospital Universitario Miguel Servet (HUMS) de Zaragoza (n=4928). Se estudió a aquellos pacientes con LDL-c y HDL- c elevados simultáneamente para ver su frecuencia y comprobar si era mayor de la esperada con respecto a la población general. Para conocer si la asociación de ambas variables era consecuencia del aumento de LDL-c, los sujetos se dividieron en dependencia de la presencia de una variante patogénica en los genes responsables de hipercolesterolemia familiar (HF). Se analizó la cohorte del NHANES 2015-2016 para estudiar la asociación entre LDL-c y HDL-c en la población general.Resultados. La elevación simultánea de LDL-c y HDL-c (>p95) es poco frecuente en la población general ya que ambas variables son independientes entre sí. En la población de la consulta con LDL-c >p95, existe un subgrupo de pacientes con HDL-c elevado (>90 mg/dL) mayor del esperado, siendo más probable presentar un HDL-c elevado en los pacientes sin HF que en aquellos con HF (OR= 13,5; p250 mg/dL y HDL-c >89 mg/dL para mujeres, y LDL-c >195 mg/dL y HDL-c >75 mg/dL para varones. Los pacientes con este fenotipo presentaron un índice de masa corporal (IMC) bajo, una tendencia a padecer menos enfermedad cardiovascular (ECV), una gamma-glutamiltransferasa (GGT) más elevada y triglicéridos normales.Conclusiones. La elevación simultánea de LDL-c y HDL-c es un fenotipo que está presente únicamente en un 1% de pacientes con dislipemia de origen desconocido. Las características clínicas y analíticas sugieren que esta hipercolesterolemia combinada constituye una entidad diferenciada de carácter multifactorial.<br /

Sistema domótico distribuido para controlar el riego y el aire acondicionado en el hogar

Este trabajo presenta el proyecto SEDomotics, realizado en la asignatura Sistemas Empotrados Distribuidos, perteneciente a la titulación del Máster en Ingeniería Informática de la Universidad Complutense de Madrid. En este trabajo se describe e implementa una plataforma de control domótico de los sistemas de riego y aire acondicionado en el hogar, utilizando para ello dos placas Arduino y una Raspberry Pi como servidor. Además de capturar los datos en tiempo real, el sistema es capaz de almacenar un histórico con dichos datos.This work presents the SEDomotics project, developed in the Distributed Embedded Systems subject, allocated within the Computer Science Master, which is taught in the Universidad Complutense de Madrid. This work describes and implements a distributed domotic system for the irrigation and air conditioner at home, using for this two Arduino boards and a Raspberry Pi as a server. In addition to capturing real time data, the system is capable of storing a record with that data.Universidad de Granada: Departamento de Arquitectura y Tecnología de Computadores; Vicerrectorado para la Garantía de la Calidad