1,876 research outputs found

    Efecto de la temperatura de termotratamiento en el comportamiento eléctrico de la madera de pino radiata

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    Se analiza el efecto de la temperatura del termotratamiento sobre la conductividad eléctrica de la madera de pino radiata. Sobre probetas de madera de pino radiata de procedencia País Vasco (España), termotratada a 190ºC y 210ºC por el método Thermowood así como sobre piezas testigo de la misma especie, procedencia y dimensiones, acondicionadas todas ellas hasta masa constante a 20ºC/40%HR, 20ºC/65%HR y 20ºC/90%HR se evaluó la resistencia eléctrica (longitudinal y transversal) y, posteriormente, se ajustó el modelo Samuelson para modelizar en cada tipo de material la relación humedad de la madera-resistencia eléctrica. Se concluye que la temperatura empleada en el tratamiento térmico de la madera afecta no sólo a la humedad de equilibrio sino, también, a su conductividad eléctrica, siendo máximo este efecto en el tratamiento efectuado a 210ºC

    Selection of extreme phenotypes: the role of clinical observation in translational research

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    Systematic collection of phenotypes and their correlation with molecular data has been proposed as a useful method to advance in the study of disease. Although some databases for animal species are being developed, progress in humans is slow, probably due to the multifactorial origin of many human diseases and to the intricacy of accurately classifying phenotypes, among other factors. An alternative approach has been to identify and to study individuals or families with very characteristic, clinically relevant phenotypes. This strategy has shown increased efficiency to identify the molecular features underlying such phenotypes. While on most occasions the subjects selected for these studies presented harmful phenotypes, a few studies have been performed in individuals with very favourable phenotypes. The consistent results achieved suggest that it seems logical to further develop this strategy as a methodology to study human disease, including cancer. The identification and the study with high-throughput techniques of individuals showing a markedly decreased risk of developing cancer or of cancer patients presenting either an unusually favourable prognosis or striking responses following a specific treatment, might be promising ways to maximize the yield of this approach and to reveal the molecular causes that explain those phenotypes and thus highlight useful therapeutic targets. This manuscript reviews the current status of selection of extreme phenotypes in cancer research and provides directions for future development of this methodology

    Cognitive Reserve Characteristics and Occupational Performance Implications in People with Mild Cognitive Impairment

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    The Cognitive Reserve hypothesis suggests that there are individual differences in the ability to cope with the pathologic changes in Alzheimer’s Disease. The proportion of elderly individuals has increased in recent years; this increase emphasizes the importance of early detection of mild cognitive impairment and the promotion of healthy ageing. The purpose of our study is to characterize cognitive reserve and occupational performance implications in people with mild cognitive impairment. 125 patients with mild cognitive impairment were enrolled. The Montreal Cognitive Assessments (MoCA) was used to evaluate cognitive status and the Cognitive Reserve Index Questionnaire (CRIq) as an indicator of cognitive reserve. Higher level of education was associated with higher MoCA scores (r = 0.290, p = 0.001). Positive significant correlations were observed between MoCA and total CRIq (r = 0.385, p < 0.001) as well as its three sub-domains, education (r = 0.231, p = 0.010), working activity (r = 0.237, p = 0.008) and leisure time (r = 0.319, p < 0.001). This study findings provide the importance of considering socio-behavioral factors in cognitive status. This research helps to describe the importance of engaging occupationally along the whole life-course as a potential protective factor in ageing, and includes a perspective of occupational therapy regarding the hypothesis of cognitive reserve.Depto. de EnfermeríaFac. de Enfermería, Fisioterapia y PodologíaTRUEpu

    Preclinical activity of LBH589 alone or in combination with chemotherapy in a xenogeneic mouse model of human acute lymphoblastic leukemia.

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    Histone deacetylases (HDACs) have been identified as therapeutic targets due to their regulatory function in chromatin structure and organization. Here, we analyzed the therapeutic effect of LBH589, a class I-II HDAC inhibitor, in acute lymphoblastic leukemia (ALL). In vitro, LBH589 induced dose-dependent antiproliferative and apoptotic effects, which were associated with increased H3 and H4 histone acetylation. Intravenous administration of LBH589 in immunodeficient BALB/c-RAG2(-/-)γc(-/-) mice in which human-derived T and B-ALL cell lines were injected induced a significant reduction in tumor growth. Using primary ALL cells, a xenograft model of human leukemia in BALB/c-RAG2(-/-)γc(-/-) mice was established, allowing continuous passages of transplanted cells to several mouse generations. Treatment of mice engrafted with T or B-ALL cells with LBH589 induced an in vivo increase in the acetylation of H3 and H4, which was accompanied with prolonged survival of LBH589-treated mice in comparison with those receiving vincristine and dexamethasone. Notably, the therapeutic efficacy of LBH589 was significantly enhanced in combination with vincristine and dexamethasone. Our results show the therapeutic activity of LBH589 in combination with standard chemotherapy in pre-clinical models of ALL and suggest that this combination may be of clinical value in the treatment of patients with ALL

    Glioblastoma on a microfluidic chip: Generating pseudopalisades and enhancing aggressiveness through blood vessel obstruction events

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    Background: Glioblastoma (GBM) is one of the most lethal tumor types. Hypercellular regions, named pseudo- palisades, are characteristic in these tumors and have been hypothesized to be waves of migrating glioblastoma cells.These “waves” of cells are thought to be induced by oxygen and nutrient depletion caused by tumor-induced blood vessel occlusion. Although the universal presence of these structures in GBM tumors suggests that they may play an instrumental role in GBM’s spread and invasion, the recreation of these structures in vitro has remained challenging. Methods: Here we present a new microfluidic model of GBM that mimics the dynamics of pseudopalisade forma- tion.To do this, we embedded U-251 MG cells within a collagen hydrogel in a custom-designed microfluidic device. By controlling the medium flow through lateral microchannels, we can mimic and control blood-vessel obstruction events associated with this disease. Results: Through the use of this new system, we show that nutrient and oxygen starvation triggers a strong migratory process leading to pseudopalisade generation in vitro.These results validate the hypothesis of pseudo- palisade formation and show an excellent agreement with a systems-biology model based on a hypoxia-driven phenomenon. Conclusions: This paper shows the potential of microfluidic devices as advanced artificial systems capable of mod- eling in vivo nutrient and oxygen gradients during tumor evolution

    Mantle-cell lymphoma genotypes identified with CGH to BAC microarrays define a leukemic subgroup of disease and predict patient outcome

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    To identify recurrent genomic changes in mantle cell lymphoma (MCL), we used high-resolution comparative genomic hybridization (CGH) to bacterial artificial chromosome (BAC) microarrays in 68 patients and 9 MCL-derived cell lines. Array CGH defined an MCL genomic signature distinct from other B-cell lymphomas, including deletions of 1p21 and 11q22.3-ATM gene with coincident 10p12-BMI1 gene amplification and 10p14 deletion, along with a previously unidentified loss within 9q21-q22. Specific genomic alterations were associated with different subgroups of disease. Notably, 11 patients with leukemic MCL showed a different genomic profile than nodal cases, including 8p21.3 deletion at tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor gene cluster (55% versus 19%; P = .01) and gain of 8q24.1 at MYC locus (46% versus 14%; P = .015). Additionally, leukemic MCL exhibited frequent IGVH mutation (64% versus 21%; P = .009) with preferential VH4-39 use (36% versus 4%; P = .005) and followed a more indolent clinical course. Blastoid variants, increased number of genomic gains, and deletions of P16/INK4a and TP53 genes correlated with poorer outcomes, while 1p21 loss was associated with prolonged survival (P = .02). In multivariate analysis, deletion of 9q21-q22 was the strongest predictor for inferior survival (hazard ratio [HR], 6; confidence interval [CI], 2.3 to 15.7). Our study highlights the genomic profile as a predictor for clinical outcome and suggests that "genome scanning" of chromosomes 1p21, 9q21-q22, 9p21.3-P16/INK4a, and 17p13.1-TP53 may be clinically useful in MCL

    Microenvironment Eradication of Hepatitis C: A Novel Treatment Paradigm

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    OBJECTIVES: Prisons are major reservoirs of hepatitis C virus (HCV) in which a therapeutic approach has been particularly difficult so far. Our aim was to create a permanent program of HCV elimination in a prison based on a "test and treat" strategy. METHODS: This open-label clinical trial was conducted in the Spanish prison "El Dueso" between May 2016 and July 2017. Viremic patients were treated with a ledipasvir-sofosbuvir regimen (8-12 weeks) according to the 2015 Spanish Guidelines. A teleconsultation program was established to follow-up patients from the hospital. Non-responders were submitted for a phylogenetic analysis and offered retreatment. An evaluation of new cases of HCV infection was performed every 6 months and upon release in all inmates. RESULTS: 847 (99.5%) inmates accepted to participate. HCV antibodies were present in 110 (13.0%) and 86 (10.2%) had detectable viremia. Most of them were genotype 1 or 3 (82.6%) and had <F2 fibrosis (52.2%). Treatment was started in the 69 inmates whose stay in prison was longer than 30 days. Sustained virological response was achieved in 64 out of 66 patients (96.9%), three of whom were successfully rescued with a salvage regimen after treatment failure. Two patients were lost to follow-up and three are currently on treatment without viremia. As a result, by July 2017 none of the 409 imprisoned was viremic, and neither reinfections nor de novo infections were detected. CONCLUSIONS: A sustained "test-and-treat" strategy against HCV in prisons is feasible and beneficial. Spreading this strategy should entail a public health impact.Supported by Plan Nacional de I+D+i 2013–2016 and Instituto de Salud Carlos III, Ministerio de Economía, Industria y Competitividad, cofinanced by European Development Regional Fund “A way to achieve Europe”,Operative program Intelligent Growth 2014–2020 and grant PIE15/00079. This study received funding assistance from Gilead Sciences, Spain (IN-ES-337-2089), C/Vía de los Poblados, 3, 28033 Madrid, Spain, http://www.gilead. com/about/worldwide-operations/europe/spain; phone number: +34 913789830), who played no part in study design, data analysis, or in the preparation of the manuscript. All study investigators declare to be independent from funders

    Nanostructured tungsten as a first wall material for the future nuclear fusion reactors

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    The lack of materials able to withstand the severe radiation conditions (high thermal loads and atomistic damage) expected in fusion reactors is the actual bottle neck for fusion to become a reality. The main requisite for plasma facing materials (PFM) is to have excellent structural stability since severe cracking or mass loss would hamper their protection role which turns out to be unacceptable. Additional practical requirements for plasma facing materials are among others: (i) high thermal shock resistance, (ii) high thermal conductivity (iii) high melting point (iv) low physical and chemical sputtering, and (v) low tritium retention

    Burden and challenges of heart failure in patients with chronic kidney disease. A call to action

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    Patients with the dual burden of chronic kidney disease (CKD) and chronic congestive heart failure (HF) experience unacceptably high rates of symptom load, hospitalization, and mortality. Currently, concerted efforts to identify, prevent and treat HF in CKD patients are lacking at the institutional level, with emphasis still being placed on individual specialty views on this topic. The authors of this review paper endorse the need for a dedicated cardiorenal interdisciplinary team that includes nephrologists and renal nurses and jointly manages appropriate clinical interventions across the inpatient and outpatient settings. There is a critical need for guidelines and best clinical practice models from major cardiology and nephrology professional societies, as well as for research funding in both specialties to focus on the needs of future therapies for HF in CKD patients. The implementation of crossspecialty educational programs across all levels in cardiology and nephrology will help train future specialists and nurses who have the ability to diagnose, treat, and prevent HF in CKD patients in a precise, clinically effective, and cost-favorable manner.Los pacientes con enfermedad renal crónica (ERC) que desarrollan insuficiencia cardíaca (IC) congestiva crónica presentan cifras inaceptablemente altas de síntomas, hospitalización y mortalidad. Actualmente, se echan en falta iniciativas institucionales dirigidas a identificar, prevenir y tratar la IC en los pacientes con ERC de manera multidisciplinar, prevaleciendo las actuaciones de las especialidades individuales. Los autores de este artículo de revisión respaldan la necesidad de crear equipos multidisciplinares cardiorrenales, en los que participen nefrólogos y enfermeras renales, que gestionen colaborativamente las intervenciones clínicas apropiadas en los entornos de pacientes con ERC e IC hospitalizados y ambulatorios. Es necesario y urgente que se elaboren guías y modelos de práctica clínica sobre la ERC con IC por parte de las sociedades profesionales de cardiología y nefrología, así como financiación para la investigación concertada entre ambas especialidades sobre la necesidad de futuros tratamientos para la IC en pacientes con ERC. La implementación de programas educativos cardiorrenales a todos los niveles en cardiología y nefrología ayudará a formar a los futuros especialistas y enfermeras para que tengan la capacidad de diagnosticar, tratar y prevenir la IC en pacientes con ERC de manera precisa, clínicamente efectiva y económicamente favorabl

    Metodología experimental aplicada a la Inmunología Molecular

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    El objetivo general del proyecto es aplicar un modelo pedagógico en el que participen los alumnos de manera activa y apliquen el método científico en base a los conocimientos que han adquirido, resolviendo y realizando un caso práctico en el laboratorio. Integra una estrategia didáctica que va a fomentar la participación activa del alumnado provocando un aprendizaje significativo, ya que el alumno tiene que resolver mediante el razonamiento un caso práctico y luego integrarlo en el laboratorio con el uso de una técnica ampliamente utilizada en Inmunología, como es la citometría de flujo.Depto. de Arquitectura de Computadores y AutomáticaFac. de InformáticaFALSEInnovasubmitte
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