Dinámica demográfica

Producción CientíficaEstudio de la situación de la población de Castilla y León (evolución, estructuras demográficas, migraciones y poblamiento).Geografí

Las cuencas mineras de Asturias, readaptación y desarrollo

Las Cuencas Mineras de Asturias (valles del Caudal y Nalón) se debaten en el momento actual entre la realidad de los desequilibrios sociodemográficos y sectoriales derivados de una crisis sin precedentes, que dura ya más de cuarenta años, y las expectativas de un futuro esperanzador, que puede abrir las puertas de una nueva etapa, la de la readaptación y recuperación, de la mano de la búsqueda de un desarrollo territorial basado en su plena integración, con nuevas funciones urbanas y rurales, dentro de un área metropolitana en fase de construcción, Ciudad Astur, motor económico y territorial de la Asturias de hoy

Análisis de la población, vivienda y comercio en Valladolid y los municipios de su alfoz

Producción CientíficaEstudio sobre la evolución de la población y la vivienda en el área comercial de la ciudad de Valladolid , sus dotaciones comerciales y desequilibrios espaciales, con el objetivo de fijar las necesidades de nuevas grandes superficies de distribución al por menor sin menoscabar el papel del pequeño comercio minorista, aplicando una gestión coordinada e integral del territorio periurbano.GEOGRAFÍAInforme encargado por IDOM

Trasplante renal en pacientes con infección por virus de la inmunodeficiencia humana (VIH)

El pronóstico de la infección por VIH ha mejorado tras introducir el tratamiento antirretroviral de gran actividad (TARGA), no contraindicando actualmente el trasplante renal (TR). La nefropatía asociada al VIH (HIVAN) es la principal causa de enfermedad crónica terminal (ERCT) en pacientes VIH a nivel mundial. Los criterios de inclusión para TR de pacientes VIH son multidisciplinares: no infecciones oportunistas; CD4>200; carga viral indetectable. Material y métodos. Revisión de historias clínicas de 14 pacientes infectados por VIH receptores de un primera lo injerto renal (2001-2019),seleccionadossegúnrecomendacionesdelasguíasespañolasyamericanas.Lainmunosupresiónserealizósegúnlaprácticahabitualennuestropaís.TARGAseinicióinmediatamentetrasTR.Resultados.LaprincipalcausadeERCTfuelaglomerulonefritis(N=6;42,9%)seguidadeHIVAN(N=4;28,6%).El71,4%(N=10)seencontrabanenhemodiálisisprevioalTRysólo1pacientesetrasplantóensituacióndeprediálisis.Desdeelpuntodevistainmuno-virológico,lamedianadeCD4fue458células/μLytodoslospacientespresentabancargaviralindetectable.El92,9%(N=13)recibíaTARGApreTR.2pacientesprecisarontrasplantectomíaprecozyfueroneliminadosdelanálisisposterior.Conunamedianadeseguimientode61,0meses,el58,3%(7/12)delospacientespresentóunafunciónretrasadadelinjertoyel33,3%(4/12)rechazoagudo.Lamedianadecreatininaalos3mesesyenlaúltimafechadeseguimientofue1,3mg/dL(RIC0,8)y2,1(RIC7,1)respectivamente.Lasupervivenciadelinjertoydelpacientea1y3añosfuede75,0%y100%;y67,0%y89,0%,respectivamente.Conclusión.ElTResunaalternativaterapéuticasegurayefectivaenpacientesseleccionadosconVIH.TheprognosisofHIVinfectionhasimprovedwiththeintroductionofhighlyactiveantiretroviraltherapy(HAART),beingnolongeracontraindicationtotransplantation(KT).HIV-associatednephropathy(HIVAN)isthemostcommoncauseofend-stagerenaldisease(ESRD)amongHIV-infectedpatientsworldwide.TheconsensuscriteriafortheselectionofHIVpatientsfortransplantationaremultidisciplinary:noopportunisticinfections;CD4count>200;undetectableviralload.Materialandmethods.Reviewoftheclinicalchartsof14HIV-infected,recipientsofaprimaryrenalallograft(2001-2019).InclusioncriteriamettheAmericanandSpanishguidelinerecommendations.Immunosuppressiveprotocolfollowedroutinepracticeinourcountry.HAARTwasstartedduringimmediatepost-KT.Results.ThemainESRDetiologywasglomerulonephritis (6;42.9%)followedbyHIVAN(4;28.6%).RegardingrenalsubstitutivetreatmentpriortoKT,themajoritywereonhemodialysis(10;71.4%).InonepatientKTwaspre-emptive.MedianCD4countwas458cells/μLandallpatientspresentedundetectableviralload.13(92.9%)wereonHAARTpriortoKT.Twopatientsunderwentearlytransplantectomy,theremainingpatientswerefollowedforamedianof61.0months(3.7to106.2months).Delayedgraftfunctionandacuterejectionratewere58.3%(7/12)and33.3%(4/12)respectively.Mediancreatininelevelsat3monthsandatthelastfollow-upwere1.3mg/dL(IQR0.8)and2.1mg/dL(IQR7.1)respectively.Graftandpatientsurvivalat1and3yearswererespectively75.0%and100%;and67.0%and89%.Conclusions.KTcanbesafeandeffectiveinselectedHIV-infectedpatient

Recursos para el autoaprendizaje en alumnos de grado y máster en la rama de conocimiento de Artes y Humanidades

Memoria ID-198. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2018-2019

CSVS, a crowdsourcing database of the Spanish population genetic variability

The knowledge of the genetic variability of the local population is of utmost importance in personalized medicine and has been revealed as a critical factor for the discovery of new disease variants. Here, we present the Collaborative Spanish Variability Server (CSVS), which currently contains more than 2000 genomes and exomes of unrelated Spanish individuals. This database has been generated in a collaborative crowdsourcing effort collecting sequencing data produced by local genomic projects and for other purposes. Sequences have been grouped by ICD10 upper categories. A web interface allows querying the database removing one or more ICD10 categories. In this way, aggregated counts of allele frequencies of the pseudo-control Spanish population can be obtained for diseases belonging to the category removed. Interestingly, in addition to pseudo-control studies, some population studies can be made, as, for example, prevalence of pharmacogenomic variants, etc. In addition, this genomic data has been used to define the first Spanish Genome Reference Panel (SGRP1.0) for imputation. This is the first local repository of variability entirely produced by a crowdsourcing effort and constitutes an example for future initiatives to characterize local variabilityworldwide. CSVS is also part of the GA4GH Beacon network.Spanish Ministry of Economy and Competitiveness SAF2017-88908-R PT17/0009/0006 PI19/00321 CIBERER ACCI-06/07/0036 PI14-948 PI171659Regional Government of Madrid, RAREGenomicsCM B2017/BMD3721 B2017/BMD-3721European Union (EU)European Union (EU) 676559University Chair UAM-IIS-FJD of Genomic MedicineRamon Areces Foundatio

Protective Role of the Interleukin 33 rs3939286 Gene Polymorphism in the Development of Subclinical Atherosclerosis in Rheumatoid Arthritis Patients

OBJECTIVES: To determine whether the interleukin-33 (IL-33)-interleukin-1 receptor like 1 (IL-1RL1) signaling pathway is implicated in the risk of subclinical atherosclerosis in patients with rheumatoid arthritis (RA). METHODS: A total of 576 Spanish RA patients from Northern Spain were genotyped for 6 well-known IL33-IL1RL1 polymorphisms (IL33 rs3939286, IL33 rs7025417, IL33 rs7044343, IL1RL1 rs2058660, IL1RL1 rs2310173 and IL1RL1 rs13015714) by TaqMan genotyping assay. The presence of subclinical atherosclerosis was determined by the assessment of carotid intima-media thickness (cIMT) by carotid ultrasound (US). RESULTS: RA patients carrying the TT genotype of the IL33 rs3939286 polymorphism had lower cIMT values than those homozygous for the CC genotype (mean ± standard deviation (SD): 0.71 ± 0.14 mm versus 0.76 ± 0.16 mm, respectively) while patients carrying the CT genotype had intermediate cIMT values (mean ± SD: 0.73 ± 0.17 mm). Moreover, RA patients carrying the mutant allele T of the IL33 rs3939286 polymorphism exhibited significantly lower cIMT values than those carrying the wild allele C (mean ± SD: 0.72 ± 0.16 mm versus 0.75 ± 0.18 mm respectively; p = 0.04). The association of both genotype and allele frequencies of IL33 rs3939286 and cIMT levels remained statistically significant after adjustment for sex, age at the time of US study, follow-up and center (p = 0.006 and p = 0.0023, respectively), evidencing that the potential effect conferred by IL33 rs3939286 may be independent of confounder factors. No association with other IL33-IL1RL1 genetic variants was observed. CONCLUSIONS: In conclusion, our results may suggest a potential protective effect of the IL33 rs3939286 allele T in the risk of subclinical atherosclerosis in patients with RA

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Regulatory sites for splicing in human basal ganglia are enriched for disease-relevant information

Genome-wide association studies have generated an increasing number of common genetic variants associated with neurological and psychiatric disease risk. An improved understanding of the genetic control of gene expression in human brain is vital considering this is the likely modus operandum for many causal variants. However, human brain sampling complexities limit the explanatory power of brain-related expression quantitative trait loci (eQTL) and allele-specific expression (ASE) signals. We address this, using paired genomic and transcriptomic data from putamen and substantia nigra from 117 human brains, interrogating regulation at different RNA processing stages and uncovering novel transcripts. We identify disease-relevant regulatory loci, find that splicing eQTLs are enriched for regulatory information of neuron-specific genes, that ASEs provide cell-specific regulatory information with evidence for cellular specificity, and that incomplete annotation of the brain transcriptome limits interpretation of risk loci for neuropsychiatric disease. This resource of regulatory data is accessible through our web server, http://braineacv2.inf.um.es/

Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies

Background Genome-wide association studies (GWAS) in Parkinson's disease have increased the scope of biological knowledge about the disease over the past decade. We aimed to use the largest aggregate of GWAS data to identify novel risk loci and gain further insight into the causes of Parkinson's disease. Methods We did a meta-analysis of 17 datasets from Parkinson's disease GWAS available from European ancestry samples to nominate novel loci for disease risk. These datasets incorporated all available data. We then used these data to estimate heritable risk and develop predictive models of this heritability. We also used large gene expression and methylation resources to examine possible functional consequences as well as tissue, cell type, and biological pathway enrichments for the identified risk factors. Additionally, we examined shared genetic risk between Parkinson's disease and other phenotypes of interest via genetic correlations followed by Mendelian randomisation. Findings Between Oct 1, 2017, and Aug 9, 2018, we analysed 7·8 million single nucleotide polymorphisms in 37 688 cases, 18 618 UK Biobank proxy-cases (ie, individuals who do not have Parkinson's disease but have a first degree relative that does), and 1·4 million controls. We identified 90 independent genome-wide significant risk signals across 78 genomic regions, including 38 novel independent risk signals in 37 loci. These 90 variants explained 16–36% of the heritable risk of Parkinson's disease depending on prevalence. Integrating methylation and expression data within a Mendelian randomisation framework identified putatively associated genes at 70 risk signals underlying GWAS loci for follow-up functional studies. Tissue-specific expression enrichment analyses suggested Parkinson's disease loci were heavily brain-enriched, with specific neuronal cell types being implicated from single cell data. We found significant genetic correlations with brain volumes (false discovery rate-adjusted p=0·0035 for intracranial volume, p=0·024 for putamen volume), smoking status (p=0·024), and educational attainment (p=0·038). Mendelian randomisation between cognitive performance and Parkinson's disease risk showed a robust association (p=8·00 × 10−7). Interpretation These data provide the most comprehensive survey of genetic risk within Parkinson's disease to date, to the best of our knowledge, by revealing many additional Parkinson's disease risk loci, providing a biological context for these risk factors, and showing that a considerable genetic component of this disease remains unidentified. These associations derived from European ancestry datasets will need to be followed-up with more diverse data. Funding The National Institute on Aging at the National Institutes of Health (USA), The Michael J Fox Foundation, and The Parkinson's Foundation (see appendix for full list of funding sources)