Cribado de alto rendimiento (hts) de una librería de pequeñas moléculas para la identificación de moléculas anti-EBOV

Motivation: Ebola virus (EBOV) is considered as the prototypical pathogen of viral hemorrhagic fever, causing severe disease and mortality rates as high as 90%. The implementation of different High-Throughput Screening systems to avoid the use of BSL-4 facilities will promote the generation of lead molecules and so the development of new therapeutics for EBOV within the next few years. The goals of the present project are directed to the discovery of new antiviral drugs against EBOV by using HTS of different libraries of small compounds, some of which have previously been an excellent source of potent antiviral compounds, by the use of a retroviral pseudotype particle (pEBOV-GFP) carrying the EBOV glycoprotein (GP).  Methods: Retroviral pseudotypes were generated by the transfection with the HIV gag-pol plasmid, pCMV-Δ8.91, the EBOV GP expression construct, pCAGGS-EBOV, and the green fluorescence protein (GFP) reporter construct, pCSGW at a ratio of 1.1:0.5:0.75 (core:envelope:reporter). At we carryed out at the IBiS the screening of different libraries of small compounds of different nature. The libraries of small compounds to be screened were synthesized by: i) the Medicinal Chemistry Institute of Madrid (IQM-CSIC), ii) the Unit of Molecular Chemistry and Pharmacology of the Institute for Research in Biomedicine of Barcelona (IRB), and iii) the Group of Organic Chemistry at the Faculty of Pharmacy of the University of Seville. Antiviral activivity was evaluated by pEBOV-mediated GFP expression.  Results: After the evaluation of 60 compounds, only compounds 4, 10, 17, 23, 33, 34, 125, 126, 279, 284, 298, 372, 385, 414 and 42 showed a significant (> 50%) inhibition of pEBOV-GFP entry (50 µM), presenting values of cytotoxicity (CC50) greater than 100 mM, therefore considered safe. Compounds 21, 371, 82, despite showing optimal inhibition percentages at 50 µM, presented CC50 values lower than our 100 µM threshold and because of that they were excluded from further evaluations. Conclusions: Although the antiviral activity of molecules identified by these system has to be confirmed against the wild-type EBOV, it is a useful tool to identify anti-EBOV candidates that also solves the necessity of work in BSL-4 facilities. Compounds identified in this work could potentially represent strong hit compounds for the development of a treatment for the EBOV disease

Digital rubric-based assessment of oral presentation competence with technological resources for preservice teachers

This study focuses on e-assessment of oral presentation competence using technology resources in a model that combines project-based learning and flipped learning. This study uses a digital rubric to assess oral presentation competence in different situations of progressive assessment for 99 preservice teachers, situations in which participation was either optional or compulsory. Findings show that the digital rubric used at various times is a methodology and a technology that facilitates the feedback process and dialogue between teachers and students about the assessment criteria. The results support future decisions for methodological design of formative assessment appropriate to online learning environments.   Evaluación basada en rúbricas digitales de la competencia de presentación oral con recursos tecnológicos para profesorado en formación Este estudio está dirigido a la e-evaluación de la competencia de presentación oral utilizando recursos tecnológicos en un modelo activo que combina aprendizaje basado en proyectos y aula invertida. Este estudio aplica el uso de una rúbrica digital para la evaluación de la competencia en presentación oral en diferentes situaciones de evaluación activa y progresiva de 99 futuros docentes en las que la participación es opcional u obligatoria. Los resultados muestran que la rúbrica digital empleada en varios momentos es una metodología y una tecnología que facilita el proceso de retroalimentación y diálogo entre docentes y estudiantes sobre los criterios de evaluación. Los resultados apoyan futuras decisiones de diseño metodológico de evaluación formativa apropiadas en entornos de aprendizaje online

Deciphering the quality of SARS-CoV-2 specific T-cell response associated with disease severity, immune memory and heterologous response

SARS-CoV-2 specific T-cell response has been associated with disease severity, immune memory and heterologous response to endemic coronaviruses. However, an integrative approach combining a comprehensive analysis of the quality of SARS-CoV-2 specific T-cell response with antibody levels in these three scenarios is needed. In the present study, we found that, in acute infection, while mild disease was associated with high T-cell polyfunctionality biased to IL-2 production and inversely correlated with anti-S IgG levels, combinations only including IFN-γ with the absence of perforin production predominated in severe disease. Seven months after infection, both non-hospitalised and previously hospitalised patients presented robust anti-S IgG levels and SARS-CoV-2 specific T-cell response. In addition, only previously hospitalised patients showed a T-cell exhaustion profile. Finally, combinations including IL-2 in response to S protein of endemic coronaviruses were the ones associated with SARS-CoV-2 S-specific T-cell response in pre-COVID-19 healthy donors’ samples. These results could have implications for protective immunity against SARS-CoV-2 and recurrent COVID-19 and may help for the design of new prototypes and boosting vaccine strategies

Diseño de un diagnóstico de peligros y riesgos laborales de los trabajadores en el área de hospitalización, del Hospital San Pedro y San Pablo del municipio de La Virginia, durante el segundo semestre del año 2015

CD-T 363.15 A94; 89 pEl procedimiento de análisis de riesgos y peligros en el área de hospitalización del Hospital San Pedro y San Pablo, es novedoso porque es la base para promover la seguridad basada en comportamientos e inculcando una cultura de autocuidado para que sea trasmitida de una generación a otra, logrando que se viva una seguridad y salud laboral por convicción más no por obligación.Universidad Libre Seccional Pereir

Twitter as a Tool for Teaching and Communicating Microbiology: The #microMOOCSEM Initiative

Online social networks are increasingly used by the population on a daily basis. They are considered a powerful tool for science communication and their potential as educational tools is emerging. However, their usefulness in academic practice is still a matter of debate. Here, we present the results of our pioneering experience teaching a full Basic Microbiology course via Twitter (#microMOOCSEM), consisting of 28 lessons of 40-45 minutes duration each, at a tweet per minute rate during 10 weeks. Lessons were prepared by 30 different lecturers, covering most basic areas in Microbiology and some monographic topics of general interest (malaria, HIV, tuberculosis, etc.). Data analysis on the impact and acceptance of the course were largely affirmative, promoting a 330% enhancement in the followers and a >350-fold increase of the number of visits per month to the Twitter account of the host institution, the Spanish Society for Microbiology. Almost one third of the course followers were located overseas. Our study indicates that Massive Online Open Courses (MOOC) via Twitter are highly dynamic, interactive, and accessible to great audiences, providing a valuable tool for social learning and communicating science. This strategy attracts the interest of students towards particular topics in the field, efficiently complementing customary academic activities, especially in multidisciplinary areas like Microbiology.Versión del edito

Usos del e‐learning en las Universidades Andaluzas: estado de la situación y análisis de buenas prácticas. (Resumen ejecutivo).

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

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

Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components. Dendritic cells (DCs) play a key role in the defense against viral infections, for instance plasmacytoid DCs (pDCs), have the capacity to produce vast amounts of interferon-alpha (IFN-α). In COVID-19 there is a deficit in DC numbers and IFN-α production, which has been associated with disease severity. In this work, we described that in addition to the DC deficiency, several DC activation and homing markers were altered in acute COVID-19 patients, which were associated with multiple inflammatory markers. Remarkably, previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+ myeloid DCs and pDCs seven months after SARS-CoV-2 infection. Moreover, the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients, while no restoration of integrin β7 and indoleamine 2,3-dyoxigenase (IDO) levels were observed. These findings contribute to a better understanding of the immunological sequelae of COVID-19

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

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 < 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

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access