38 research outputs found

    El espacio narrativo en El Señor de los Anillos.

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    The work consists of an analysis of the narrative space in the trilogy The Lord of the Rings, by J.R.R. Tolkien. The analysis was carried out by dividing the space into three levels: location, scope of performance, and spatial configuration. Examples and quotes of each level are provided from each part of the novel

    Long-Term Changes of Inflammatory Biomarkers in Individuals on Suppressive Three-Drug or Two-Drug Antiretroviral Regimens

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    Background: Because inflammation is associated with mortality and has been linked to HIV transcription in lymphoid tissues during ART, it is necessary to address the long-term effects of switching 3-drug (3DR) to 2-drug regimens (2DR) on inflammation. Methods: Nested study in the Spanish AIDS Research Network. We selected PWH ART-naive initiating 3DR who achieved viral suppression in the first 48 weeks and either remained on 3DR or switched to 2DR (3TC+bPI; 3TC+DTG; DTG+RPV). We assessed the trajectories on inflammatory markers during ART using multivariate piecewise mixed models. Results: We analyzed 619 plasma samples from 148 patients (3DR, N=90; 2DR, N=58), the median follow-up was 4.6 (IQR 3.2-6.2) years. There were no significant differences in baseline characteristics between groups. After adjusting for potential confounders, patients with 3DR experienced a slow decline of IL6, hs-CRP, sCD14, sCD163, and D-dimer over time. In contrast, compared to 3DR, switching to 2DR was associated with increases in IL-6 (p=0.001), hs-CRP (p=0.003), and D-dimer (p=0.001) after year 3 from virologic suppression. 2DR was associated with a higher risk of hs-CRP quartile increase (aOR 3.3, 95%CI 1.1-10) and D-dimer quartile increase (aOR 3.7, 95%CI 1.1-13). The adjusted biomarker trajectories did not reveal a distinct pattern according to the type of 2DR used (bPI vs DTG). Conclusions: In this study in virally suppressed individuals, maintaining 3DR was associated with a more favorable long-term inflammatory profile than switching to 2DR. The potential clinical implications of these findings on the development of non-AIDS events deserve further investigation.The HIV BioBank, integrated in the Spanish AIDS Research Network, is supported by Instituto de Salud Carlos III, Spanish Health Ministry (Grant n° proyectos RD06/0006/0035, RD12/0017/0037 and RD16/0025/0019) as part of the Plan Nacional R + D + I and co-financed by the European Development Regional Fund ‘‘A way to achieve Europe’’ (ERDF). The RIS Cohort (CoRIS) is funded by the Instituto de Salud Carlos III through the Red Temática de Investigación Cooperativa en SIDA (RIS C03/173, RD12/0017/0018 and RD16/0002/0006) as part of the Plan Nacional R+D+I and cofinanced by ISCIII-Subdirección General de Evaluacion and Fondo Europeo de Desarrollo Regional (FEDER)”. This work was supported by the Instituto de Salud Carlos III projects AC17/00019, PI18/00154, ICI20/00058, CIBER de Enfermedades Infecciosas, and Gilead Sciences (Investigator Sponsored Research ISR-17-10192). The funders had no role in the study design, data analysis, or in the interpretation of the results.S

    Microglia regulate learning and memory through NF-κB

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    Resumen del póster presentado al 19th Meeting Spanish Society of Neuroscience, celebrado en Lleida del 3 al 5 de noviembre de 2021.Microglia, the resident immune cells of the CNS, have been implicated in brain plasticity and function. However, the mechanisms remain largely unknown. Here, we show that Cre-dependent removal of the RelA subunit of the NF-κB transcription factor from adult microglia results in impaired learning and long-term potentiation. Depletion of RelA elicits changes in chromatin accessibility and transcriptome landscapes of microglia associated with specific gene regulatory programs driving the activation of specific microglia phenotypes. Our findings suggest that NF-κB gene products drive specific microglia phenotypes modulating neuronal circuits for learning and memory.Peer reviewe

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

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    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

    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

    Modelling and characterization of scr Catalyst for onboard monitoring and Diagnostics

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    [ES] El objetivo del proyecto es el estudio y caracterización del funcionamiento de un catalizador de Reducción Catalítica Selectiva (SCR) instalado en un motor diésel. Dicho proyecto nace de la necesidad de monitorizar y diagnosticar el estado del catalizador así como de reducir las emisiones de Amoníaco y Óxidos de nitrógeno mediante la implementación de nuevos algoritmos de control que utilicen técnicas de análisis de contenido en frecuencia y por tanto puedan hacer que el catalizador funcione de forma más eficiente. Para ello es necesario aprender nuevos lenguajes de programación como Matlab, con el cuál se calibra el modelo de simulación del catalizador y se procesan y analizan los datos obtenidos mediante equipos de adquisición durante los ensayos en banco de ensayos. También es necesario aprender cómo funciona el protocolo de comunicación CAN Bus, para poder conectar diversos dispositivos al motor con el fin de realizar un control activo en algunos actuadores electromecánicos. Toda esta comunicación con el motor ha sido posible gracias a la plataforma de prototipado rápido dSpace, la cual hay que configurar mediante Simulink y Control Desk y nos permite mantener comunicación CAN con el motor. Estos dos últimos lenguajes de programación también es necesario abordarlos en cierta medida a la hora de realizar los ensayos, para realizar pequeñas variaciones a la hora de ejecutar los test en banco de ensayo. Por último y no menos importante, es necesario conocer el funcionamiento de la sala de ensayos, que implica los protocolos de seguridad, las rutinas de calentamiento y enfriamiento del motor antes y después de cada ensayo, así como el manejo del software de control STARS e INCA para controlar el dinamómetro del banco de ensayos así como hacer variaciones en los parámetros por defecto de la unidad de control del motor (ECU).Valenzuela Galera, S. (2018). Modelado y caracterización de catalizador SCR para el desarrollo de métodos embarcados de monitorización y diagnóstico. Universitat Politècnica de València. http://hdl.handle.net/10251/11156

    Redundant and exclusive roles of cbp and p300 in neural progenitors proliferation and differentiation

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    Trabajo presentado al 17th Meeting of the Spanish Society for Developmental Biology (SEBD), celebrado de forma virtual del 18 al 20 de noviembre de 2020.Peer reviewe
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