La precisión diagnóstica de los péptidos natriuréticos en la insuficiencia cardiaca: una revisión sistemática y metaanálisis en el paciente agudo: The diagnostic accuracy of the natriuretic peptides in heart failure: systematic review and diagnostic meta-analysis in the acute care setting. Roberts E, Ludman AJ, Dworzynski K at el. BMJ 2015;350:H910

Los péptidos natriuréticos forman una familia de proteínas con acción hormonal que tienen efecto sobre el balance del sodio y del agua. Hasta el momento, se han identificado 5 tipos de péptidos natriuréticos, 2 de ellos son secretados por las células del miocardio: el péptido natriurético atrial o tipo A (del inglés: atrial natriuretic peptide type A; ANP) se sintetiza y secreta principalmente en las aurículas, y se almacena en forma de gránulos como prohormona (proANP), cuando se segrega es dividida por una proteasa en un fragmento terminal (NT-proANP) y en una molécula biológicamente activa (ANP). A nivel intermedio se aísla la región media o fragmento central del ANP (del inglés; MidRegional Atrial Natriuretic Peptide; MR-ProANP), que ha sido descrito como un buen marcador biológico. El péptido natriurético tipo B, también llamado cerebral, debido a que inicialmente se aisló en tejido cerebral porcino (del inglés: atrial natriuretic peptide type B, BNP), es un péptido estructuralmente similar al ANP, el cual se sintetiza como una prohormona (proBNP), principalmente por los miocitos ventriculares, más en el ventrículo izquierdo y, en menor cantidad, en el tejido auricular y por fibroblastos cardiacos, y se escinde en una molécula activa (BNP) y otra inactiva (del inglés, propéptido cerebral natriurético N terminal; NT-proBNP). Cómo hacer un diagnóstico correcto en pacientes con sospecha de insuficiencia cardíaca (IC) aguda es en ocasiones un reto, ya que sólo en un 40-50% de los casos es posible una confirmación diagnóstica (1,2). Varios estudios han demostrado que cuando a la historia clínica, al examen clínico, y a las investigaciones convencionales, se le añade la medición de los niveles de péptidos natriuréticos plasmáticos se mejora la precisión diagnóstica (3,4). Ello ha dado lugar a que estos marcadores se hayan incluido en las recomendaciones internacionales para la diagnóstico y tratamiento de la IC. En el año 2012 la Sociedad Europea de Cardiología incluyó los valores de corte específicos de los diferentes péptidos natriuréticos para la exclusión de fallo cardiaco agudo independientemente de la edad (5). Basado en consensos de expertos, se han establecido los siguientes puntos de corte para la exclusión de la IC aguda: ≤100 ng/L para el BNP, ≤300 ng/L para el NTproBNP y ≤120 pmol/L para el MRproANP. Ya es conocido su uso en el diagnóstico de exclusión de la IC crónica en el ámbito ambulatorio, pero su utilidad en el paciente agudo es incierto ya que su papel no está bien definido y además no existe apenas disponibilidad de medición en los Servicios de Urgencias

Cannabinoid CB1 receptor gene inactivation in oligodendrocyte precursors disrupts oligodendrogenesis and myelination in mice

[EN] Cannabinoids are known to modulate oligodendrogenesis and developmental CNS myelination. However, the cell-autonomous action of these compounds on oligodendroglial cells in vivo, and the molecular mechanisms underlying these effects have not yet been studied. Here, by using oligodendroglial precursor cell (OPC)-targeted genetic mouse models, we show that cannabinoid CB1 receptors exert an essential role in modulating OPC differentiation at the critical periods of postnatal myelination. We found that selective genetic inactivation of CB1 receptors in OPCs in vivo perturbs oligodendrogenesis and postnatal myelination by altering the RhoA/ROCK signaling pathway, leading to hypomyelination, and motor and cognitive alterations in young adult mice. Conversely, pharmacological CB1 receptor activation, by inducing E3 ubiquitin ligase-dependent RhoA proteasomal degradation, promotes oligodendrocyte development and CNS myelination in OPCs, an effect that was not evident in OPC-specific CB1 receptor-deficient mice. Moreover, pharmacological inactivation of ROCK in vivo overcomes the defects in oligodendrogenesis and CNS myelination, and behavioral alterations found in OPC-specific CB1 receptor-deficient mice. Overall, this study supports a cell-autonomous role for CB1 receptors in modulating oligodendrogenesis in vivo, which may have a profound impact on the scientific knowledge and therapeutic manipulation of CNS myelination by cannabinoids.This work was supported by the MINECO grants SAF2017-83516 and PID2020-112640RB-I00, and the Comunidad de Madrid grants 2016-T1/BMD-1060 and 2020-5 A/BMD-19728, Atraccion del Talento Investigador Program, to JP. AHG and TA. AHG was also supported by the Comunidad de Madrid contract PEJD-2017PRE/BMD-3703, and A.S.T by Fundacion Tatiana Perez de Guzman el Bueno. Support was also provided by MINECO (grants RTI2018-095311-B-I00 to MG. and SAF2016-75292-R to CM), CIBERNED (grants CB06/05/0005 to M.G. and CB06/0005/0076 to C.M.), FEDER and ISCIII (AES 2018 grants PI18-00941 to IG-R and PI18/00513 to SM), Basque Government (grants IT1203-19 to C.M. and PIBA19-0059 to SM), and ARSEP Foundation (grant to SM)

A method to establish marine bio-regions in the pelagic ecosystem based on phytoplanktonic communities. Aplication to the southern Spanish coast

Bioregions in the pelagic ecosystem are frequently established on the basis of remotely sensed properties of the sea surface, such as sea surface temperature or sea surface chlorophyll concentration. Those works dealing with the regionalization of the marine ecosystem by means of the use of properties of the water column are less frequent, and even less those that obtain the data from periodic in situ monitoring programs, which are scarce. In this work we use time series of micro, nano and pico-phytoplanktonic abundances in the upper 100 m of the continental shelves of the Gulf of Cadiz and the Alboran Sea from the projects STOCA and RADMED (southern coast of Spain, Western Mediterranean). The use of times series allows us to estimate the median phytoplanktonic abundances of several phytoplanktonic groups along the water column. These statistics differ substantially from those abundances obtained for one particular campaign, reflecting the large seasonal and inter-annual variability of phytoplanktonic communities. These median profiles, estimated for the four seasons of the year and for several phytoplanktonic groups characterize each of the locations sampled in the aforementioned monitoring programs and are used for establishing the similarity between them. Then, these locations are grouped using a cluster analysis. Using some simulations from numerical experiments we determine which metrics and methods of analysis are the more suitable ones for the regionalization of the area of study. A bootstrap method is also used to determine which differences among bioregions can be considered as statistically significant. Despite the existence of a fast current that connects the Gulf of Cadiz and the Alboran Sea, our results show that the outer part of the Gulf of Cadiz shelf, and that of the Alboran Sea, can be considered as two differentiated bioregions. The latter region shows a higher productivity with a higher abundance of large cells such as diatoms, and the dominance of Synechococcus bacteria over Prochlorococcus ones

Cohort profile: the MCC-Spain follow-up on colorectal, breast and prostate cancers: study design and initial results

PURPOSE: Since 2016, the multicase-control study in Spain (MCC-Spain) has focused towards the identification of factors associated with cancer prognosis. Inception cohorts of patients with colorectal, breast and prostate cancers were assembled using the incident cases originally recruited. PARTICIPANTS: 2140 new cases of colorectal cancer, 1732 of breast cancer and 1112 of prostate cancer were initially recruited in 12 Spanish provinces; all cancers were incident and pathologically confirmed. Follow-up was obtained for 2097 (98%), 1685 (97%) and 1055 (94.9%) patients, respectively. FINDINGS TO DATE: Information gathered at recruitment included sociodemographic factors, medical history, lifestyle and environmental exposures. Biological samples were obtained, and 80% of patients were genotyped using a commercial exome array. The follow-up was performed by (1) reviewing medical records; (2) interviewing the patients by phone on quality of life; and (3) verifying vital status and cause of death in the Spanish National Death Index. Ninety-seven per cent of recruited patients were successfully followed up in 2017 or 2018; patient-years of follow-up were 30 914. Most colorectal cancers (52%) were at clinical stage II or lower at recruitment; 819 patients died in the follow-up and the 5-year survival was better for women (74.4%) than men (70.0%). 71% of breast cancers were diagnosed at stages I or II; 206 women with breast cancer died in the follow-up and the 5-year survival was 90.7%. 49% of prostate cancers were diagnosed at stage II and 32% at stage III; 119 patients with prostate cancer died in the follow-up and the 5-year survival was 93.7%. FUTURE PLANS: MCC-Spain has built three prospective cohorts on highly frequent cancers across Spain, allowing to investigate socioeconomic, clinical, lifestyle, environmental and genetic variables as putative prognosis factors determining survival of patients of the three cancers and the inter-relationship of these factors

Risk factors for unfavorable outcome and impact of early post-transplant infection in solid organ recipients with COVID-19: A prospective multicenter cohort study

The aim was to analyze the characteristics and predictors of unfavorable outcomes in solid organ transplant recipients (SOTRs) with COVID-19. We conducted a prospective observational cohort study of 210 consecutive SOTRs hospitalized with COVID-19 in 12 Spanish centers from 21 February to 6 May 2020. Data pertaining to demographics, chronic underlying diseases, transplantation features, clinical, therapeutics, and complications were collected. The primary endpoint was a composite of intensive care unit (ICU) admission and/or death. Logistic regression analyses were performed to identify the factors associated with these unfavorable outcomes. Males accounted for 148 (70.5%) patients, the median age was 63 years, and 189 (90.0%) patients had pneumonia. Common symptoms were fever, cough, gastrointestinal disturbances, and dyspnea. The most used antiviral or host-targeted therapies included hydroxychloroquine 193/200 (96.5%), lopinavir/ritonavir 91/200 (45.5%), and tocilizumab 49/200 (24.5%). Thirty-seven (17.6%) patients required ICU admission, 12 (5.7%) suffered graft dysfunction, and 45 (21.4%) died. A shorter interval between transplantation and COVID-19 diagnosis had a negative impact on clinical prognosis. Four baseline features were identified as independent predictors of intensive care need or death: advanced age, high respiratory rate, lymphopenia, and elevated level of lactate dehydrogenase. In summary, this study presents comprehensive information on characteristics and complications of COVID-19 in hospitalized SOTRs and provides indicators available upon hospital admission for the identification of SOTRs at risk of critical disease or death, underlining the need for stringent preventative measures in the early post-transplant period

Practical guideline for Benign paroxismal positional vertigo

Introduction and objective: Benign paroxysmal positional vertigo (BPPV) is the most common peripheral vertigo, characterized by brief attacks of rotatory vertigo associated with nystagmus, which are elicited by specific changes in head position relative to gravity. The observation of positional nystagmus is essential for the diagnosis of BPPV. The treatment consists in maneuvers of canalith repositioning procedure to move otoconial debris from the affected semicircular canal to the utricle. These guidelines are intended for all who treat the BPPV in their work, with an intention to assist in the diagnosis and application of an appropriate therapeutic method. Method: The experience and analysis of different national and international consensus on BPPV, has allowed to a large group of ENT specialists of the Communities of Castilla y León, Cantabria and La Rioja (Spain), carry out this guide. Results: The different clinical entities are reviewed. BPPV of the posterior semicircular canal, horizontal canal and anterior canal, BPPV affecting several canals, atypical and central BPPV, subjective BPPV and the characteristics of this process in the elderly. Canalith repositioning procedures have been illustrated with explanatory drawings. Discussion and conclusions: Although the pathophysiology of BPPV is canalolithiasis comprising free-floating otoconial debris within the endolymph of a semicircular canal, or cupulolithiasis comprising otoconial debris adherent to the cupula, there are still many issues to be resolved. We think that the best way to find answers is part of using a common methodology in the diagnosis and treatment of these patients.Introducción y Objetivo: El vértigo periférico más frecuente es el Vértigo Posicional Paroxístico Benigno (VPPB), caracterizado por bruscos ataques de sensación rotatoria, que aparecen como consecuencia de determinados cambios en la posición de la cabeza con relación a la gravedad. La observación del nistagmo posicional es fundamental para el diagnóstico de VPPB. El tratamiento consiste en aplicar maniobras de reposición, para intentar trasladar los restos otoconiales libres, desde el conducto semicircular (CS) afectado hasta el utrículo. Esta guía, está orientada para quienes tratan el VPPB, con la intención práctica de ayudarles en el diagnóstico y tratamiento de esta enfermedad. Método: La experiencia y el análisis de diferentes acuerdos nacionales e internacionales sobre el VPPB, han permitido a un amplio grupo de especialistas ORL de las Comunidades de Castilla y León, Cantabria y La Rioja (España), llevar a cabo esta guía. Resultados: Se revisan las diferentes entidades clínicas. VPPB del conducto semicircular posterior (CSP), horizontal (CSA) y anterior (CSA), incluyéndose también el VPPB multicanal, VPPB atípico y central, VPPB subjetivo y las características de este proceso en el anciano. Las maniobras de reposición se han ilustrado con dibujos explicativos. Discusión y conclusiones: Aunque la fisiopatología del VPPB se explica por la presencia de restos otoconiales libres en la endolinfa de uno o varios conductos semicirculares (canalitiasis) y en algunos casos por su adherencia a la cúpula del CS (cupulolitiasis), aún quedan muchas cuestiones por resolver. Pero creemos que la mejor manera de encontrar respuestas parte de utilizar una metodología común en el diagnóstico y tratamiento de estos pacientes

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

Novel genes and sex differences in COVID-19 severity

[EN] Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.S

EstuPlan: Methodology for the development of creativity in the resolution of scientific and social problems

[EN] Creative thinking is necessary to generate novel ideas and solve problems. "EstuPlan" is a methodology in which knowledge and creativity converge for the resolution of scientific problems with social projection. It is a training programme that integrates teachers, laboratory technicians and PhD students, master and undergraduate students which form working groups for the development of projects. Projects have a broad and essential scope and projection in terms of environmental problems, sustainable use of natural resources, food, health, biotechnology or biomedicine. The results show the success of this significant learning methodology using tools to develop creativity in responding to scientific and social demand for problem-solving to transfer academic knowledge to different professional environments. Bioplastics, Second Life of Coffee, LimBio, Algae oils, Ecomers, Caring for the life of your crop and Hate to Deforestate are currently being developed.Astudillo Calderón, S.; De Díez De La Torre, L.; García Companys, M.; Ortega Pérez, N.; Rodríguez Martínez, V.; Alzahrani, S.; Alonso Valenzuela, R.... (2019). EstuPlan: Methodology for the development of creativity in the resolution of scientific and social problems. En HEAD'19. 5th International Conference on Higher Education Advances. Editorial Universitat Politècnica de València. 711-717. https://doi.org/10.4995/HEAD19.2019.9205OCS71171