Grape Resveratrol Increases Serum Adiponectin and Downregulates Inflammatory Genes in Peripheral Blood Mononuclear Cells: A Triple-Blind, Placebo-Controlled, One-Year Clinical Trial in Patients with Stable Coronary Artery Disease

This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.[Purpose] The grape and wine polyphenol resveratrol exerts cardiovascular benefits but evidence from randomized human clinical trials is very limited. We investigated dose-depending effects of a resveratrol-containing grape supplement on stable patients with coronary artery disease (CAD) treated according to currently accepted guidelines for secondary prevention of cardiovascular disease.[Methods] In a triple-blind, randomized, placebo-controlled, one-year follow-up, 3-arm pilot clinical trial, 75 stable-CAD patients received 350 mg/day of placebo, resveratrol-containing grape extract (grape phenolics plus 8 mg resveratrol) or conventional grape extract lacking resveratrol during 6 months, and a double dose for the following 6 months. Changes in circulating inflammatory and fibrinolytic biomarkers were analyzed. Moreover, the transcriptional profiling of inflammatory genes in peripheral blood mononuclear cells (PBMCs) was explored using microarrays and functional gene expression analysis.[Results] After 1 year, in contrast to the placebo and conventional grape extract groups, the resveratrol-containing grape extract group showed an increase of the anti-inflammatory serum adiponectin (9.6 %, p = 0.01) and a decrease of the thrombogenic plasminogen activator inhibitor type 1 (PAI-1) (−18.6 %, p = 0.05). In addition, 6 key inflammation-related transcription factors were predicted to be significantly activated or inhibited, with 27 extracellular-space acting genes involved in inflammation, cell migration and T-cell interaction signals presenting downregulation (p < 0.05) in PBMCs. No adverse effects were detected in relation to the study products.[Conclusions] Chronic daily consumption of a resveratrol-containing grape nutraceutical could exert cardiovascular benefits in stable-CAD patients treated according to current evidence-based standards, by increasing serum adiponectin, preventing PAI-1 increase and inhibiting atherothrombotic signals in PBMCs.This study was supported by public funds: Projects CICYT-BFU2007-60576 and Consolider-Ingenio 2010 (CSD2007-00063, Fun-C-Food) from the Spanish Ministry of Science and Innovation (MICINN) and GERM-06-04486 (Fundación Séneca, Murcia, Spain). Dr. Tomé-Carneiro received a FPI grant from MICINN and Dr. Larrosa received a JAE-DOC contract from the Consejo Superior de Investigaciones Científicas (CSIC, Spain).Peer reviewe

A Study About Meta-Optimizing the NSGA-II Multi-Objective Evolutionary Algorithm.

The automatic design of multi-objective metaheuristics is an active research line aimed at, given a set of problems used as training set, to find the configuration of a multi-objective optimizer able of solving them efficiently. The expected outcome is that the auto-configured algorithm can be used of find accurate Pareto front approximations for other problems. In this paper, we conduct a study on the meta-optimization of the wellknown NSGA-II algorithm, i.e., we intend to use NSGA-II as an automatic configuration tool to find configurations of NSGA-II. This search can be formulated as a multi-objective problem where the decision variables are the NSGA-II components and parameters and the the objectives are quality indicators that have to be minimized. To develop this study, we rely on the jMetal framework. The analysis we propose is aimed at answering the following research questions: RQ1 - how complex is to build the meta-optimization package?, and RQ2 - can accurate configurations be found? We conduct an experimentation to give an answer to these questions.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Quantic Analysis of Formation of a Biomaterial of Latex, Retinol, and Chitosan for Biomedical Applications

The present work shows the quantum theoretical analysis and practical tests for the formation of a homogeneous mixture with Latex (Lx), Chitosan (Qn) and Retinol (Rl), which work as possible biomaterial for regeneration of epithelial tissue. Lx, Qn, and Rl compounds molecules were designed through Hyperchem to get the coefficient of electrostatic potential calculations. The amounts used to create the biomaterial are minimum depending on the quantities of molecules used in chemical design. A positive calculation was obtained for the reaction of these three compounds and the formation of the biomaterial in physical checking theory etc

Quantic Analysis of the Adherence of a Gram-Negative Bacteria in A HEPA Filter

It is known that Gram-negative bacteria (GNB) are the most frequent bacteria in hospital units. It is also known that GNBs generate a greater number of nosocomial infections in critical areas. In the present work, the adhesion of the bacterial cell wall (BCW) to the compounds of the material layers of a high efficiency filter (HEPA) was analyzed. The analysis was carried out by means of molecular simulation and quantum chemistry. The BCW and HEPA molecules were designed using Hyperchem software for simulation. The calculations of the quantum interactions of the molecules were carried out using the theory of the electron transfer coefficient (ETC). It obtained from 4 to 6 compounds that are more likely to interact even as a chemical reaction. The compounds of the glass fibers are the ones that work best for the adhesion and destruction of the BCW

Mutations in the MORC2 gene cause axonal Charcot-Marie-Tooth disease

[EN] Charcot-Marie-Tooth disease (CMT) is a complex disorder with wide genetic heterogeneity. Here we present a new axonal Charcot-Marie-Tooth disease form, associated with the gene microrchidia family CW-type zinc finger 2 (MORC2). Whole-exome sequencing in a family with autosomal dominant segregation identified the novel MORC2 p. R190W change in four patients. Further mutational screening in our axonal Charcot-Marie-Tooth disease clinical series detected two additional sporadic cases, one patient who also carried the same MORC2 p. R190W mutation and another patient that harboured a MORC2 p. S25L mutation. Genetic and in silico studies strongly supported the pathogenicity of these sequence variants. The phenotype was variable and included patients with congenital or infantile onset, as well as others whose symptoms started in the second decade. The patients with early onset developed a spinal muscular atrophy-like picture, whereas in the later onset cases, the initial symptoms were cramps, distal weakness and sensory impairment. Weakness and atrophy progressed in a random and asymmetric fashion and involved limb girdle muscles, leading to a severe incapacity in adulthood. Sensory loss was always prominent and proportional to disease severity. Electrophysiological studies were consistent with an asymmetric axonal motor and sensory neuropathy, while fasciculations and myokymia were recorded rather frequently by needle electromyography. Sural nerve biopsy revealed pronounced multifocal depletion of myelinated fibres with some regenerative clusters and occasional small onion bulbs. Morc2 is expressed in both axons and Schwann cells of mouse peripheral nerve. Different roles in biological processes have been described for MORC2. As the silencing of Charcot-Marie-Tooth disease genes have been associated with DNA damage response, it is tempting to speculate that a deregulation of this pathway may be linked to the axonal degeneration observed in MORC2 neuropathy, thus adding a new pathogenic mechanism to the long list of causes of Charcot-Marie-Tooth disease.This collaborative joint project is awarded by IRDiRC and funded by the Instituto de Salud Carlos III (ISCIII) - Subdireccion General de Evaluacion y Fomento de la Investigacion within the framework of the National R+D+I Plan (IR11/TREAT-CMT to T.S., S.I.P.P., F.P. and C.E.; PI12/00453 to C.E.; and PI12/0946 to T.S.), co-funded with FEDER funds. Additional support was provided by the Ramon Areces Foundation and by the ISCIII and the Centro de Investigacion Principe Felipe (CPII14/00002) to C.E.Sevilla, T.; Lupo, V.; Martínez-Rubio, D.; Sancho, P.; Sivera, R.; Chumillas, MJ.; García-Romero, M.... (2016). Mutations in the MORC2 gene cause axonal Charcot-Marie-Tooth disease. Brain. 139:62-72. https://doi.org/10.1093/brain/awv311627213

Diseño de estrategias conjuntas UA-centros de secundaria para el fomento del conocimiento de disciplinas científico-técnicas

Continuando con la línea emprendida por el Instituto Universitario de Ingeniería de Procesos Químicos, para desarrollar actividades de fomento del conocimiento de disciplinas de ciencia y tecnología, se ha convocado el “VI Certamen de Proyectos Educativos de Ingeniería Química” durante el curso 2013-2014. Con dicha actividad se pretende promover el interés por estudios relacionados con las disciplinas científico-técnicas, entre los alumnos de ESO, con una mejor conceptualización, comprensión y caracterización de los temas. Para ello, se diseñan, planifican y desarrollan acciones entre profesorado de la UA y centros de secundaria, sobre el papel de la Química en la industria para mejorar la calidad de vida. En la presente edición del certamen se han inscrito 13 centros, que han presentado un total de 20 proyectos, relacionados con los siguientes temas: la Ingeniería Química y el medio ambiente, la Ingeniería Química y la industria alimentaria, la Ingeniería Química y el mundo de los plásticos, la Ingeniería Química y la energía y la Ingeniería Química «Verde» sostenible

Paleofitogeografía de los pinares en las montañas periféricas de la cuenca del Duero

En las dos últimas décadas se han obtenido numerosos resultados procedentes de diferentes trabajos paleobotánicos (Cuaternario final) realizados en los territorios montanos periféricos de la depresión del Duero. Las metodologías empleadas han sido diversas y tienen que ver con los diferentes tipos de yacimientos y de muestras biológicas seleccionadas para su estudio; entre ellas destacan las técnicas de microscopía óptica para la identificación de maderas subfósiles, la morfología comparada de macrorrestos y los estudios dendrocronológicos en árboles longevos y maderas subfósiles. En esta comunicación se reúnen y resumen los trabajos más importantes, haciéndose una síntesis de las conclusiones obtenidas en los trabajos paleofitogeográficos realizados hasta el momento; se hace hincapié en la información proporcionada por los macrorrestos (maderas, estróbilos) así como por la recogida en los registros dendrocronológicos (con extensión a la dendroecología). Otro de los objetivos de la comunicación es la síntesis de las conclusiones obtenidas en los trabajos paleofitogeográficos realizados hasta el momento. Uno de esos resultados es que el comportamiento de los pinares a lo largo del Holoceno presenta diferentes modalidades en cada una de las cordilleras que bordean la cuenca del Duero; desde casos con marcada estabilidad a otros en que se muestran variaciones temporales apreciables (con patrones de heterogeneidad en función de un eje N-S y/o O-E

Seguimiento del Grado en Óptica y Optometría

En el marco del proyecto de Redes de Investigación en Docencia Universitaria 2013-14 de la Universidad de Alicante se creó una red de trabajo formada por los profesores coordinadores de semestre del Grado en Óptica y Optometría y dos alumnos. Dado que durante el curso académico 2013-14 ha tenido lugar la implantación del último curso del Grado en Óptica y Optometría, el objetivo principal de esta red ha sido la realización de un análisis de la implantación del título así como el estudio del diseño y desarrollo del Trabajo Fin de Grado y del programa de Prácticas Externas. Para ello se han recogido las sugerencias y propuestas realizadas a través de las comisiones de semestres, de la comisión de garantía de calidad y de reuniones con el alumnado, con el fin de optimizar el funcionamiento del título, tanto en la distribución de contenidos, como en las metodologías docentes y de evaluación de las distintas materias que componen el plan de estudios

Unraveling heterogeneous susceptibility and the evolution of breast cancer using a systems biology approach

This is an Open Access article distributed under the terms of the Creative Commons Attribution License.-- et al.[Background]: An essential question in cancer is why individuals with the same disease have different clinical outcomes. Progress toward a more personalized medicine in cancer patients requires taking into account the underlying heterogeneity at different molecular levels. [Results]: Here, we present a model in which there are complex interactions at different cellular and systemic levels that account for the heterogeneity of susceptibility to and evolution of ERBB2-positive breast cancers. Our model is based on our analyses of a cohort of mice that are characterized by heterogeneous susceptibility to ERBB2-positive breast cancers. Our analysis reveals that there are similarities between ERBB2 tumors in humans and those of backcross mice at clinical, genomic, expression, and signaling levels. We also show that mice that have tumors with intrinsically high levels of active AKT and ERK are more resistant to tumor metastasis. Our findings suggest for the first time that a site-specific phosphorylation at the serine 473 residue of AKT1 modifies the capacity for tumors to disseminate. Finally, we present two predictive models that can explain the heterogeneous behavior of the disease in the mouse population when we consider simultaneously certain genetic markers, liver cell signaling and serum biomarkers that are identified before the onset of the disease. [Conclusions]: Considering simultaneously tumor pathophenotypes and several molecular levels, we show the heterogeneous behavior of ERBB2-positive breast cancer in terms of disease progression. This and similar studies should help to better understand disease variability in patient populations.JPL was partially supported by FEDER and MICINN (PLE2009-119), FIS (PI07/0057, PI10/00328, PIE14/00066), the Junta de Castilla y León (SAN673/SA26/08; SAN126/SA66/09, SA078A09, CSI034U13), the “Fundación Eugenio Rodríguez Pascual”, the Fundación Inbiomed (Instituto Oncológico Obra Social de la Caja Guipozcoa-San Sebastian, Kutxa), and the “Fundación Sandra Ibarra de Solidaridad frente al Cáncer”. AC was supported by MICINN (PLE2009-119). SCLL is funded by a JAEdoc Fellowship (CSIC)/FSE. MMSF and ABG are funded by fellowships from the Junta de Castilla y Leon. WR was supported by a Forschungsstipendium of the Deutsche Forschungsgemeinschaft (DFG) [RE 3108/1-1]. TN, BPB and DYL acknowledge support from the US Department of Energy Low-Dose SFA Program at Berkeley Lab [DE-AC02-05CH11231], the National Institutes of Health [RC1NS069177] and the California Breast Cancer Research Program [15IB-0063]. JHM was supported by the National Institutes of Health, a National Cancer Institute grant (R01 CA116481), and the Low-Dose Scientific Focus Area, Office of Biological and Environmental Research, US Department of Energy (DE-AC02-05CH11231).Peer Reviewe

Similar incidence of coronavirus disease 2019 (COVID-19) in patients with rheumatic diseases with and without hydroxychloroquine therapy

Background Hydroxychloroquine is not efficacious as post-exposure prophylaxis against coronavirus disease 2019 (COVID-19). It is not known whether as pre-exposure prophylaxis it may prevent COVID-19. Objective To compare the incidence of COVID-19 in Spanish patients with autoimmune rheumatic diseases treated with and without hydroxychloroquine. Patients and methods Retrospective electronic record review, from February 27th to June 21st, 2020, of patients with autoimmune inflammatory diseases followed at two academic tertiary care hospitals in Seville, Spain. The cumulative incidence of confirmed COVID-19, by PCR or serology, was compared between patients with and without hydroxychloroquine as part of their treatment of autoimmune inflammatory diseases. Results Among 722 included patients, 290 (40%) were receiving hydroxychloroquine. During the seventeen-week study period, 10 (3.4% [95% CI: 1.7%-6.7%] cases of COVID-19 were registered among patients with hydroxychloroquine and 13 (3.0% [1.6%-5.1%]) (p = 0.565) in those without hydroxychloroquine. COVID-19 was diagnosed by PCR in four (1.4%, 95% CI 0.38%-3.5%) subject with hydroxychloroquine and six (1.4%, 95% CI 0.5%-3.0%) without hydroxychloroquine (p = 0.697). Three patients on hydroxychloroquine and four patients without hydroxychloroquine were admitted to the hospital, none of them required to be transferred to the intensive care unit and no patient died during the episode. Conclusions The incidence and severity of COVID-19 among patients with autoimmune rheumatic diseases with and without hydroxychloroquine was not significantly different.Instituto de Salud Carlos III I3SNSMinisterio de Ciencia, Innovación y Universidades CP18/0014