33 research outputs found

    Higher constitutive IL15Rα expression and lower IL‐15 response threshold in coeliac disease patients

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    The IL-15 triggering effect of gliadin is not exclusive to coeliac disease (CD) patients, whereas the secondary response is CD specific. We have studied the expression of the IL-15 receptor, and the IL-15 response upon stimulation, in non-CD and CD patients, and the possible existence of a lower immunological threshold in the latter. Forty-two CD patients (20 on a gluten-containing diet, GCD, and 22 on gluten-free diet, GFD) and 24 non-CD healthy individuals were studied. IL15Rα mRNA expression, and tissue characterization, were assayed in the duodenum. Biopsies from six CD patients on GFD and 10 non-CD individuals were studied in vitro using organ culture in basal conditions, as well as after IL-15 stimulation discarding basal IL-15 production. Secretion of immune mediators was measured in the culture supernatants. IL15Rα mRNA expression was increased in CD patients, as compared with non-CD controls (on GFD P = 0·0334, on GCD P = 0·0062, respectively), and confirmed also by immunofluorescence. No differences were found between CD patients on GFD and on GCD. After in vitro IL-15 stimulation, IL15Rα expression was only triggered in non-CD controls (P = 0·0313), though it remained increased in CD patients. Moreover, IL-15 induced a more intense immunological response in CD patients after triggering the production of both nitrites and IFNγ (P = 0·0313, P = 0·0313, respectively). Gliadin-induced IL15 has a lower response threshold in CD patients, leading to the production of other immune mediators and the development of the intestinal lesion, and thus magnifying its effects within the CD intestine.Facultad de Ciencias ExactasLaboratorio de Investigaciones del Sistema Inmun

    Villasviejas del Tamuja (Botija, Cáceres). Desvelamiento del paisaje urbano de un Castro de la Edad del Hierro

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    Editor: Victorino Mayoral Herrera.El objetivo de la presente monografía es dar a conocer a la comunidad científica y al conjunto de la ciudadanía, los resultados de las últimas investigaciones desarrolladas en el castro de Villasviejas del Tamuja (Botija, provincia de Cáceres). Se reúnen en ella las aportaciones de un amplio grupo de profesionales que han trabajado de manera coordinada durante tres años en este sitio arqueológico emblemático de la Protohistoria peninsular. Se trata, no obstante, del fruto de una colaboración científica mucho más larga, cuyos ejes temáticos responden a dos grandes líneas de investigación potenciadas desde el Instituto de Arqueología-Mérida (Consejo Superior de Investigaciones Científicas/Junta de Extremadura, IAM en lo sucesivo). Por un lado, el estudio de las comunidades de la Segunda Edad del Hierro y el impacto provocado por la conquista romana, con un especial énfasis en su dimensión territorial y socioeconómica. Por otro, la experimentación y aplicación de los métodos no destructivos en Arqueología, como una vía para obtener un conocimiento extensivo de las transformaciones en paisajes y asentamientos a través del tiempo.Esta monografía ha sido realizada dentro del proyecto de investigación Desarrollo de métodos de mínima invasión para la revalorización socio-cultural de zonas arqueológicas (Ref. IB16150) financiado por la Consejería de Economía, Comercio e Innovación de la Junta de Extremadura.Peer reviewe

    Hugo Chávez: una década en el poder

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    Una década de Hugo Chávez Frías y su proyecto político en Venezuela trajo consigo un cambio de paradigmas que llama la atención de la sociedad en general. Este libro es el resultado del esfuerzo conjunto de un grupo de académicos de distintas nacionalidades que desde sus líneas de investigación realizan análisis que le brindan al lector elementos para comprender de manera global lo que significa una década de gobierno del Presidente Chávez en Venezuela.Este libro es el resultado del esfuerzo conjunto de un grupo de académicos de distintas nacionalidades que desde sus líneas de investigación realizan análisis que le brindan al lector elementos para comprender de manera global lo que significa una década de gobierno del Presidente Chávez en Venezuela

    Novedades corológicas y nomenclaturales para la flora vascular de la Sierra de Gredos (Sistema Central), III

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    In the present paper we present the floristic novelties for the flora of the Sierra de Gredos resulting from the explorations of these mountains and that, mostly, are the result of the field trips of the year 2021. We present 31 chorological novelties, among which we highlight the finding in the Community of Madrid of the restricted endemic Iberodes brassicifolia (Lag.) M. Serrano, R. Carbajal & S. Ortiz. Also relevant are Herniaria hirsuta L., Rosa glauca Pourr. (new for the Spanish Central System) and Rosa coriifolia Fr. (new for Extremadura and the whole of the Sierra de Gredos), as well as Soliva sessilisRuiz & Pav., Trifolium vesiculosumSavi (new for Castilla y León) and Lepidium villarsii Gren. & Godr. subsp. villarsii (new for the Sierra de Gredos). Finally, two new nomenclatural combinations are made in the genus Tephroseris (Rchb.) Rchb.: Tephroseris balbisiana (DC.) Holub subsp. coincy (Rouy) P. Vargas & Luceño, endemic to Gredos range, and Tephroseris balbisiana subsp. elodes (Boiss. ex DC.) P. Vargas & Luceño, endemic to Sierra Nevada

    Role of age and comorbidities in mortality of patients with infective endocarditis

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    [Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

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

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    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

    Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

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    Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p &lt; 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics
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