Métodos indirectos para la estimación de poblaciones ocultas.

En determinadas situaciones podemos encontrar dificultades a la hora de calcular prevalencias en algunas poblaciones. Es el caso de personas que tienen comportamientos que son difíciles de identificar debido a que pueden estar sancionados socialmente o ser ilegales. Es lo que llamamos poblaciones ocultas. Este artículo proporciona una revisión crítica de los métodos más utilizados para calcular el tamaño de una población de difícil acceso. Se trata de métodos indirectos, que estiman la prevalencia de una población oculta basándose en fuentes de datos incompletas. Se exponen diferentes métodos, cada uno de ellos tiene diferentes indicaciones para ser utilizado, dependiendo de los datos de los que dispongamos. Además, precisan de una serie de requisitos para poder ser aplicados y cada uno está expuesto a diferentes tipos de sesgos. Por estos motivos, hay que valorar correctamente los datos disponibles para aplicar el método más preciso, y si fuese posible, utilizar simultáneamente varios métodos para poder comparar los resultados obtenidos, además de valorar críticamente los resultados y comprobar si se ajustan a la realidad.Estimating the prevalence of the so-called “hidden populations” can be challenging, because the identification of its members is difficult due to their socially sanctionable or illegal behaviors. This article provides a critical review of the most widely used methods for estimating the size of a hard-to-reach population. All are indirect methods, based on incomplete data sources. Depending on the available data, one method can be more appropriate than another. Besides, each method must fulfill a number of requirements, and each one may be subject to specific risk of bias. To choose the most suitable method, an accurate evaluation of the available data is necessary, and. if possible several methods should be used simultaneously to be able to compare the results and to critically evaluate if these results fit with the reality.Parcialmente financiado por “Ministerio de Economía y Competitividad, Actuación de Formación Posdoctoral” (FPDI-2013-15827)

Indirect methods to estimate hidden population

Estimating the prevalence of the so-called "hidden populations" can be challenging, because the identification of its members is difficult due to their socially sanctionable or illegal behaviors. This article provides a critical review of the most widely used methods for estimating the size of a hard-to-reach population. All are indirect methods, based on incomplete data sources. Depending on the available data, one method can be more appropriate than another. Besides, each method must fulfill a number of requirements, and each one may be subject to specific risk of bias. To choose the most suitable method, an accurate evaluation of the available data is necessary, and. if possible several methods should be used simultaneously to be able to compare the results and to critically evaluate if these results fit with the reality. En determinadas situaciones podemos encontrar dificultades a la hora de calcular prevalencias en algunas poblaciones. Es el caso de personas que tienen comportamientos que son difíciles de identificar debido a que pueden estar sancionados socialmente o ser ilegales. Es lo que llamamos poblacio-nes ocultas. Este artículo proporciona una revisión crítica de los métodos más utilizados para calcular el tamaño de una población de difícil acceso. Se trata de métodos indirectos, que estiman la prevalencia de una población oculta basándose en fuentes de datos incompletas. Se exponen diferentes métodos, cada uno de ellos tiene diferentes indicaciones para ser utilizado, dependiendo de los datos de los que dispongamos. Además, precisan de una serie de requisitos para poder ser aplicados y cada uno está expuesto a di-ferentes tipos de sesgos. Por estos motivos, hay que valorar correctamente los datos disponibles para aplicar el método más preciso, y si fuese posible, utilizar simultáneamente varios métodos para poder comparar los resultados obtenidos, además de valorar críticamente los resultados y comprobar si se ajustan a la realidad.Palabras clave: Poblaciones Vulnerables, Métodos Epidemiológicos, Vigilancia Epidemiológica, Recogida de Datos.Financiación: parcialmente financiado por “Ministerio de Economía y Competitividad, Actuación de Formación Posdoctoral” (FPDI-2013-15827).S

Indirect methods to estimate hidden population: Second part.

Las poblaciones ocultas, aquellas difíciles de identificar por tener características estigmatizadoras o ilegales, suelen dar problemas a la hora de determinar su tamaño o prevalencia en determinados contextos. Los métodos tradicionales o directos, como las encuestas poblacionales, no suelen servir para este cometido. Los métodos indirectos, que parten de fuentes de datos incompletas para estimar la prevalencia real de la población, sí pueden ser útiles. Este trabajo completa el artículo original publicado en 2017 por Revista Española de Salud Pública sobre métodos indirectos para la estimación de poblaciones ocultas. Se exponen cuatro métodos diferentes, cada uno de los cuales tiene distintas indicaciones dependiendo de los datos de los que dispongamos y diferentes sesgos que deben valorarse detenidamente para realizar una estimación lo más cercana posible a la realidad. "Hidden populations" are difficult to identify because they have stigmatizing or illegal characteristics. For that reason, determining their size or prevalence in certain contexts is complicated. In those populations, raditional or direct methods, as population surveys, do not usually serve for this purpose, but indirect methods, based on incomplete data sources, can be useful.This work completes the original article published in Revista Española de Salud Pública in 2017: "Indirect methods to estimate hidden populations". Different methods are exposed, showing their indications and bias. To make an estimation as real as possible it is necessary to evaluate carefully the data available and analyze the risk of bias.Financiación: parcialmente financiado por “Ministerio de Economía y Competitividad,Actuación de Formación Posdoctoral” (FPDI-2013-15827)”S

Influence of Demographic and Lifestyle Variables on Plasma Magnesium Concentrations and Their Associations with Cardiovascular Risk Factors in a Mediterranean Population

Several studies have shown that a low magnesium (Mg) intake in the diet is associated with greater cardiovascular risk and greater risk of diabetes. However, the results are not consistent in all populations. To minimize the biases derived from diet measurement, more objective biomarkers of magnesium status have been proposed. Although there is still no ideal biomarker for Mg, several studies have shown that plasma Mg concentrations could be a relatively acceptable biomarker for cardiovascular risk assessment. However, further studies are required to better characterize this marker in different populations. Our aim was to analyze the association between plasma Mg concentrations (measured through inductively coupled plasma mass spectrometry (ICP-MS)) methods, and cardiovascular risk factors in individuals from a general Mediterranean population (aged 18–80 years). The influence of demographic and lifestyle variables, including adherence to the Mediterranean diet, on plasma Mg concentrations was analyzed. The mean Mg level of the population studied was 0.77 ± 0.08 mmol/L, the prevalence of hypomagnesemia (<0.70 mmol/L) being 18.6%. We did not find any statistically significant differences between plasma Mg concentrations and sex, age, tobacco smoking and total adherence to the Mediterranean diet (p > 0.05). We found a statistically significant association between plasma Mg concentrations and the prevalence of type-2 diabetes (0.77 ± 0.08 mmol/L in non-diabetics versus 0.73 ± 0.13 mmol/L in diabetics; p = 0.009). Despite the low prevalence of type-2 diabetes in this population (11.24% in subjects with hypomagnesemia versus 3.91%, in normomagnesemia; p = 0.005), hypomagnesemia was associated with greater odds of being diabetic in comparison with normomagnesemia (OR = 3.36; p = 0.016, even after adjustment for sex, age, obesity, and medications). On the other hand, no statistically significant association of plasma Mg concentrations with obesity, hypertension, fasting triglycerides, HDL-cholesterol or uric acid was found. However, in contrast to what was initially expected, a statistically significant association was found between plasma Mg concentrations (basically in the highest quartile) and greater total cholesterol (p < 0.05) and LDL-cholesterol concentrations (p < 0.05). In conclusion, our results contribute to increasing the evidence gathered by numerous studies on the inverse association between hypomagnesemia and type-2 diabetes, as well as to the observation, previously reported in some studies, of a direct association with hypercholesterolemia. This paradoxical link should be deeply investigated in further studies.This study was partially funded, by the Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional (FEDER) (grants CIBER 06/03, SAF2016–80532-R); the Junta de Andalucía (AGR145 research group); the University Jaume I (grant P1–1B2013–54); the Fundació La Marató de TV3 (grant 538/U/2016) and the Generalitat Valenciana (grants PROMETEO2017/017, and APOSTD/2019/136)

Usos del e-learning en las Universidades Andaluzas: Estado de la situación y análisis de buenas prácticas. (Versión completa)

Secretaría General de Universidades, Investigación y Tecnología P07-SE-J.0267

The outcome of boosting mitochondrial activity in alcohol-associated liver disease is organ-dependent.

BACKGROUND AND AIMS Alcohol-associated liver disease (ALD) accounts for 70% of liver-related deaths in Europe, with no effective approved therapies. Although mitochondrial dysfunction is one of the earliest manifestations of alcohol-induced injury, restoring mitochondrial activity remains a problematic strategy due to oxidative stress. Here, we identify methylation-controlled J protein (MCJ) as a mediator for ALD progression and hypothesize that targeting MCJ may help in recovering mitochondrial fitness without collateral oxidative damage. APPROACH AND RESULTS C57BL/6 mice [wild-type (Wt)] Mcj knockout and Mcj liver-specific silencing (MCJ-LSS) underwent the NIAAA dietary protocol (Lieber-DeCarli diet containing 5% (vol/vol) ethanol for 10 days, plus a single binge ethanol feeding at day 11). To evaluate the impact of a restored mitochondrial activity in ALD, the liver, gut, and pancreas were characterized, focusing on lipid metabolism, glucose homeostasis, intestinal permeability, and microbiota composition. MCJ, a protein acting as an endogenous negative regulator of mitochondrial respiration, is downregulated in the early stages of ALD and increases with the severity of the disease. Whole-body deficiency of MCJ is detrimental during ALD because it exacerbates the systemic effects of alcohol abuse through altered intestinal permeability, increased endotoxemia, and dysregulation of pancreatic function, which overall worsens liver injury. On the other hand, liver-specific Mcj silencing prevents main ALD hallmarks, that is, mitochondrial dysfunction, steatosis, inflammation, and oxidative stress, as it restores the NAD + /NADH ratio and SIRT1 function, hence preventing de novo lipogenesis and improving lipid oxidation. CONCLUSIONS Improving mitochondrial respiration by liver-specific Mcj silencing might become a novel therapeutic approach for treating ALD.This work was supported by grants from Ministerio de Ciencia e Innovación, Programa Retos-Colaboración RTC2019-007125-1 (for Jorge Simon and Maria Luz Martinez-Chantar); Ministerio de Economía, Industria y Competitividad, Retos a la Sociedad AGL2017- 86927R (for F.M.); Instituto de Salud Carlos III, Proyectos de Investigación en Salud DTS20/00138 and DTS21/00094 (for Jorge Simon and Maria Luz Martinez-Chantar, and Asis Palazon. respectively); Instituto de Salud Carlos III, Fondo de Investigaciones Sanitarias co-founded by European Regional Development Fund/European Social Fund, “Investing in your future” PI19/00819, “Una manera de hacer Europa” FIS PI20/00765, and PI21/01067 (for Jose J. G. Marin., Pau Sancho-Bru,. and Mario F. Fraga respectively); Departamento de Industria del Gobierno Vasco (for Maria Luz Martinez-Chantar); Asturias Government (PCTI) co-funding 2018-2023/ FEDER IDI/2021/000077 (for Mario F. Fraga.); Ministerio de Ciencia, Innovación y Universidades MICINN: PID2020-117116RB-I00, CEX2021-001136-S PID2020-117941RB-I00, PID2020-11827RB-I00 and PID2019-107956RA-100 integrado en el Plan Estatal de Investigación Científica y Técnica y Innovación, cofinanciado con Fondos FEDER (for Maria Luz Martinez-Chantar, Francisco J Cubero., Yulia A Nevzorova and Asis Palazon); Ayudas Ramón y Cajal de la Agencia Estatal de Investigación RY2013-13666 and RYC2018- 024183-I (for Leticia Abecia and Asis Palazon); European Research Council Starting Grant 804236 NEXTGEN-IO (for Asis Palazon); The German Research Foundation SFB/TRR57/P04, SFB1382-403224013/ A02 and DFG NE 2128/2-1 (for Francisco J Cubero and Yulia A Nevzorova); National Institute of Health (NIH)/National Institute of Alcohol Abuse and Alcoholism (NIAAA) 1U01AA026972-01 (For Pau Sancho-Bru); Junta de Castilla y León SA074P20 (for Jose J. G. Marin); Junta de Andalucía, Grupo PAIDI BIO311 (for Franz Martin); CIBERER Acciones Cooperativas y Complementarias Intramurales ACCI20-35 (for Mario F. Fraga); Ministerio de Educación, Cultura y Deporte FPU17/04992 (for Silvia Ariño); Fundació Marato TV3 201916-31 (for Jose J. G. Marin.); Ainize Pena-Cearra is a fellow of the University of the Basque Country (UPV/ EHU); BIOEF (Basque Foundation for Innovation and Health Research); Asociación Española contra el Cáncer (Maria Luz Martinez-Chantar and Teresa C. Delgado.); Fundación Científica de la Asociación Española Contra el Cáncer (AECC Scientific Foundation) Rare Tumor Calls 2017 (for Maria Luz Martinez-Chantar); La Caixa Foundation Program (for Maria Luz Martinez-Chantar); Proyecto Desarrollo Tecnologico CIBERehd (for Maria Luz Martinez-Chantar); Ciberehd_ISCIII_MINECO is funded by the Instituto de Salud Carlos III.S

Integrative epigenomics in Sjögren´s syndrome reveals novel pathways and a strong interaction between the HLA, autoantibodies and the interferon signature

Primary Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The etiology of SS is complex with environmental triggers and genetic factors involved. By conducting an integrated multi-omics study, we confirmed a vast coordinated hypomethylation and overexpression effects in IFN-related genes, what is known as the IFN signature. Stratified and conditional analyses suggest a strong interaction between SS-associated HLA genetic variation and the presence of Anti-Ro/SSA autoantibodies in driving the IFN epigenetic signature and determining SS. We report a novel epigenetic signature characterized by increased DNA methylation levels in a large number of genes enriched in pathways such as collagen metabolism and extracellular matrix organization. We identified potential new genetic variants associated with SS that might mediate their risk by altering DNA methylation or gene expression patterns, as well as disease-interacting genetic variants that exhibit regulatory function only in the SS population. Our study sheds new light on the interaction between genetics, autoantibody profiles, DNA methylation and gene expression in SS, and contributes to elucidate the genetic architecture of gene regulation in an autoimmune population

Complement component C4 structural variation and quantitative traits contribute to sex-biased vulnerability in systemic sclerosis

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER), "A way of making Europe".Copy number (CN) polymorphisms of complement C4 play distinct roles in many conditions, including immune-mediated diseases. We investigated the association of C4 CN with systemic sclerosis (SSc) risk. Imputed total C4, C4A, C4B, and HERV-K CN were analyzed in 26,633 individuals and validated in an independent cohort. Our results showed that higher C4 CN confers protection to SSc, and deviations from CN parity of C4A and C4B augmented risk. The protection contributed per copy of C4A and C4B differed by sex. Stronger protection was afforded by C4A in men and by C4B in women. C4 CN correlated well with its gene expression and serum protein levels, and less C4 was detected for both in SSc patients. Conditioned analysis suggests that C4 genetics strongly contributes to the SSc association within the major histocompatibility complex locus and highlights classical alleles and amino acid variants of HLA-DRB1 and HLA-DPB1 as C4-independent signals

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality