Procesos asociados al control de la infección por el virus VIH: Caracterización a nivel molecular/celular.

En la búsqueda de dianas celulares que actúen contra el VIH-1 y permitan erradicar el virus del organismo, el estudio de factores genéticos tanto del hospedador como del virus, que condicionan el curso de la enfermedad, así como de factores de restricción en el huésped, proteínas celulares que interfieren con mecanismos del virus, suponen las estrategias más prometedoras. Desde el punto de vista de los factores virales, hemos estudiado la funcionalidad del gen env procedente virus VIH-1 de un clúster de pacientes LTNP-EC. Nuestro trabajo ha permitido identificar deficiencias en la señalización de dicho complejo de envoltura (Env) viral, a través de CD4, la cual es necesaria para la eficiente entrada viral, impidiéndoles promover la estabilización de los microtúbulos acetilados y la reorganización de la actina en el fenómeno del “capping”, correspondiéndose dichos defectos con una menor entrada viral e infectividad. La secuencia conservada de estas Env condiciona estas deficiencias funcionales y es coherente con el fenotipo clínico LTNP-EC del clúster. Asimismo, estudiando la enzima celular HDAC6 como factor de restricción contra la poliproteína estructural Pr55-Gag del VIH-1, identificamos que la interacción entre estas proteínas y la consiguiente degradación de Pr55-Gag por ruta autofágica, no dependía del dominio BUZ de HDAC6. Mutaciones en los dominios NC, SP2 y p6 de Pr55-Gag, interferían con esta degradación. Estos resultados abren camino a identificar las regiones exactas de interacción entre estas proteínas, descartando el dominio BUZ de unión a ubiquitina

HIV-1 Nef Targets HDAC6 to Assure Viral Production and Virus Infection

HIV Nef is a central auxiliary protein in HIV infection and pathogenesis. Our results indicate that HDAC6 promotes the aggresome/autophagic degradation of the viral polyprotein Pr55Gag to inhibit HIV-1 production. Nef counteracts this antiviral activity of HDAC6 by inducing its degradation and subsequently stabilizing Pr55Gag and Vif viral proteins. Nef appears to neutralize HDAC6 by an acidic/endosomal-lysosomal processing and does not need the downregulation function, since data obtained with the non-associated cell-surface Nef-G2A mutant – the cytoplasmic location of HDAC6 – together with studies with chemical inhibitors and other Nef mutants, point to this direction. Hence, the polyproline rich region P72xxP75 (69–77 aa) and the di-Leucin motif in the Nef-ExxxLL160-165 sequence of Nef, appear to be responsible for HDAC6 clearance and, therefore, required for this novel Nef proviral function. Nef and Nef-G2A co-immunoprecipitate with HDAC6, whereas the Nef-PPAA mutant showed a reduced interaction with the anti-HIV-1 enzyme. Thus, the P72xxP75 motif appears to be responsible, directly or indirectly, for the interaction of Nef with HDAC6. Remarkably, by neutralizing HDAC6, Nef assures Pr55Gag location and aggregation at plasma membrane, as observed by TIRFM, promotes viral egress, and enhances the infectivity of viral particles. Consequently, our results suggest that HDAC6 acts as an anti-HIV-1 restriction factor, limiting viral production and infection by targeting Pr55Gag and Vif. This function is counteracted by functional HIV-1 Nef, in order to assure viral production and infection capacities. The interplay between HIV-1 Nef and cellular HDAC6 may determine viral infection and pathogenesis, representing both molecules as key targets to battling HIV

HIV-1 envelope glycoproteins isolated from viremic non-progressor individuals are fully functional and cytopathic

International audienc

Enfermedades crónicas

Adherencia al tratamiento farmacológico y relación con el control metabólico en pacientes con DM2Aluminio en pacientes con terapia de reemplazo renal crónico con hemodiálisis en Bogotá, ColombiaAmputación de extremidades inferiores: ¿están aumentando las tasas?Consumo de edulcorantes artificiales en jóvenes universitariosCómo crecen niños normales de 2 años que son sobrepeso a los 7 añosDiagnóstico con enfoque territorial de salud cardiovascular en la Región MetropolitanaEfecto a corto plazo de una intervención con ejercicio físico, en niños con sobrepesoEfectos de la cirugía bariátrica en pacientes con síndrome metabólico e IMC < 35 KG/M2Encuesta mundial de tabaquismo en estudiantes de profesiones de saludEnfermedades crónicas no transmisibles: Consecuencias sociales-sanitarias de comunidades rurales en ChileEpidemiología de las muertes hospitalarias por patologías relacionadas a muerte encefálica, Chile 2003-2007Estado nutricional y conductas alimentarias en adolescentes de 4º medio de la Región de CoquimboEstudio de calidad de vida en una muestra del plan piloto para hepatitis CEvaluación del proceso asistencial y de resultados de salud del GES de diabetes mellitus 2Factores de riesgo cardiovascular en población universitaria de la Facsal, universidad de TarapacáImplicancias psicosociales en la génesis, evolución y tratamiento de pacientes con hipertensión arterial esencialInfarto agudo al miocardio (IAM): Realidad en el Hospital de Puerto Natales, 2009-2010Introducción de nuevas TIC y mejoría de la asistencia a un programa de saludNiños obesos atendidos en el Cesfam de Puerto Natales y su entorno familiarPerfil de la mortalidad por cáncer de cuello uterino en Río de JaneiroPerfil del paciente primo-consultante del Programa de Salud Cardiovascular, Consultorio Cordillera Andina, Los AndesPrevalencia de automedicación en mujeres beneficiarias del Hospital Comunitario de Til-TiPrevalencia de caries en población preescolar y su relación con malnutrición por excesoPrevalencia de retinopatía diabética en comunas dependientes del Servicio de Salud Metropolitano Occidente (SSMOC)Problemas de adherencia farmacológica antihipertensiva en población mapuche: Un estudio cualitativoRol biológico de los antioxidantes innatos en pacientes portadores de VIH/SidaSobrepeso en empleados de un restaurante de una universidad pública del estado de São Paul

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Adelante / Endavant

Séptimo desafío por la erradicación de la violencia contra las mujeres del Institut Universitari d’Estudis Feministes i de Gènere "Purificación Escribano" de la Universitat Jaume

The microwave-assisted organocatalyzed rearrangement of Propargyl vinyl ethers to salicylaldehydes derivatives

Trabajo presentado en el 19th European Symposium of Organic Chemistry, celebrado en Lisboa del 12 al 16 de julio de 2015.Propargyl vinyl ethers constitute a privileged group of small size, densely functionalized and readily accessible linear scaffolds. The main key to the chemical reactivity encoded in these structures is the [3,3]-sigmatropic rearrangement (propargyl Claisen rearrangement) shown in Scheme 1A, which takes place irreversibly and under thermodynamic control to generate the allene 2 which isomerizes to dienal. We have developed a microwave-assisted, catalytic (imidazole 10 mol-%) and scalable methodologyto transform these allenes into salicylaldehyde motives supported on a broad range of topologies, which spanned from simple aromatic monocycles to complex fused polycyclic systems. The reaction manifold is depicted in Scheme 1B. We have performed a theoretical study of this reaction which is in full agreement with the observed experimental results. The reaction scope and the proposed mechanism will be commented in our presentation.This research was supported by the Spanish Ministerio de Economía y Competitividad (MINECO), and the European FEDER and Regional Development Fund (CTQ2011-28417-C01-02). L. Cotos and D.M. thank MICINN and CSIC for a FPI and a JAE-PRE grant respectively.Peer Reviewe

The microwave-assisted organocatalyzed rearrangement of Propargyl vinyl ethers to salicylaldehydes derivatives

Trabajo presentado en la reunión XXXV Bienal de la Real Sociedad Española de Química, celebrada en A Coruña del 19 al 23 de julio de 2015.Propargyl vinyl ethers constitute a privileged group of small size, densely functionalized and readily accessible linear scaffolds. The main key to the chemical reactivity encoded in these structures is the [3,3]-sigmatropic rearrangement (propargyl Claisen rearrangement) shown in Scheme 1A, which takes place irreversibly and under thermodynamic control to generate the allene 2 which isomerizes to dienal. We have developed a microwave-assisted, catalytic (imidazole 10 mol-%) and scalable methodologyto transform these allenes into salicylaldehyde motives supported on a broad range of topologies, which spanned from simple aromatic monocycles to complex fused polycyclic systems. The reaction manifold is depicted in Scheme 1B. We have performed a theoretical study of this reaction which is in full agreement with the observed experimental results. The reaction scope and the proposed mechanism will be commented in our presentation.This research was supported by the Spanish Ministerio de Economía y Competitividad (MINECO), and the European FEDER and Regional Development Fund (CTQ2011-28417- C01-02). L. Cotos and D.M. thank MICINN and CSIC for a FPI and a JAE-PRE grant respectively.Peer Reviewe

Zika Virus Pathogenesis: A Battle for Immune Evasion

Zika virus (ZIKV) infection and its associated congenital and other neurological disorders, particularly microcephaly and other fetal developmental abnormalities, constitute a World Health Organization (WHO) Zika Virus Research Agenda within the WHO’s R&D Blueprint for Action to Prevent Epidemics, and continue to be a Public Health Emergency of International Concern (PHEIC) today. ZIKV pathogenicity is initiated by viral infection and propagation across multiple placental and fetal tissue barriers, and is critically strengthened by subverting host immunity. ZIKV immune evasion involves viral non-structural proteins, genomic and non-coding RNA and microRNA (miRNA) to modulate interferon (IFN) signaling and production, interfering with intracellular signal pathways and autophagy, and promoting cellular environment changes together with secretion of cellular components to escape innate and adaptive immunity and further infect privileged immune organs/tissues such as the placenta and eyes. This review includes a description of recent advances in the understanding of the mechanisms underlying ZIKV immune modulation and evasion that strongly condition viral pathogenesis, which would certainly contribute to the development of anti-ZIKV strategies, drugs, and vaccines.Depto. de Genética, Fisiología y MicrobiologíaFac. de Ciencias BiológicasTRUEpu

Productive Performance and Cecum Microbiota Analysis of Broiler Chickens Supplemented with β-Mannanases and Bacteriophages—A Pilot Study

This study was conducted to evaluate the productive performance, intestinal health, and description of the cecum microbiota in broilers supplemented with β-mannanases (MNs) and bacteriophages (BPs). Six hundred one-day-old broilers were divided into four groups and fed one of the following diets: CON—corn–soybean meal + 10 ppm enramycin (ENR); MN: CON + 500 ppm MN; BP: CON + 500 ppm BP; MN + BP: BP + 500 ppm MN. The BP and MN factors showed similar performances to ENR. MN improved the concentration of IgA in the jejunum at 35 days of age. The morphometric index (IM) of the thymus increased by adding MN, while BP increased the liver and thymus IM. The histological analysis showed that BP and MN improved the intestinal morphology. MN + BP showed a tendency to decrease the abundance of Proteobacteria and increase the abundance of Bacteroidetes, indicating better microbiota function. In conclusion, our results demonstrate that the combination of MN + BP has potential in poultry nutrition; however, we highly recommend further experiments to confirm this hypothesis