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Myotonic dystrophy type 1 (DM1) is a multisystemic neuromuscular genetic disease with an estimated prevalence of approximately at least half a million individuals based on its vast ethnic variation. Building upon a well-known physiopathology and several proof-of-concept therapeutic approaches, herein we compile a comprehensive overview of the most recent drug development programs under preclinical and clinical evaluation. Specifically, close to two dozen drug developments, eight of which are already in clinical trials, explore a diversity of new chemical entities, drug repurposing, oligonucleotide, and gene therapy-based approaches. Of these, repurposing of tideglusib, mexiletine, or metformin appear to be therapies with the most potential to receive marketing authorization for DM1.

Chemotherapy is the only systemic treatment approved for pancreatic ductal adenocarcinoma (PDAC), with a selection of regimens based on patients' performance status and expected efficacy. The establishment of a potent stratification associated with chemotherapeutic efficacy could potentially improve prognosis by tailoring treatments., info:eu-repo/semantics/published

La impresión 3D es un sector que se encuentra en auge en la actualidad. A pesar de ser una tecnología que empezó a desarrollarse a principios de la década de los años noventa. La innovación y desarrollo de esta técnica engloba multitud de áreas y aplicaciones diversas: alimentación, moda, regeneración de tejidos. En esta última, se han logrado grandes avances mediante la utilización de biomateriales compatibles como el colágeno, alginato, PLA, en diferentes formatos: esferas, hidrogeles, biorreactores o micro-chips. Logrando crear mediante la utilización de estos biomateriales y la impresión 3D, dispositivos o scaffolds; dónde después del aislamiento y la siembra de las propias células del paciente, se puede realizar un cultivo 3D y posteriormente, introducir este dispositivo en el paciente, logrando cerrar una lesión. En este ensayo se diseña e imprime un dispositivo mediante impresión 3D, como soporte para la siembra y el estudio del crecimiento, proliferación y migración de líneas celulares o estudios de migración celular. Se utilizaran las células de la línea tumoral de glioblastoma humano, U87. Se emplearan los factores 2-desoxy-D-glucosa y el factor de crecimiento neuronal B27 como estímulos para evaluar el crecimiento y la migración de estas células. El desarrollo de esta técnica puede ser una herramienta válida para realizar estudios de movilidad celular como estudios de migración en metástasis o quimiotaxis. 3D printing is a sector that is booming today. Despite being a technology that began to develop in the early 1990's. The innovation and development of this technique encompasses many different areas and applications such as food, fashion and tissue regeneration. In the latter, great advances have been achieved by the use of compatible biomaterials such as collagen, alginate, PLA, in different spheres, hydrogels, bioreactors or microchips. Achieving create by using these biomaterials and 3D printing, devices or scaffolds; where after isolation and seeding of the patient's own cells in them, a 3D culture can be performed and subsequently, introduce this device into the patient, managing to close an injury. In this assay a device is designed and printed by 3D printing as a support for planting and studying the growth, proliferation and migration of cell lines or cell migration studies. The cells of the human glioblastoma tumor line, U87, will be used. The factors 2-desoxy-D-glucose and B27 neuronal growth factor will be used as stimuli to evaluate the growth and migration of these cells. The development of this technique can be a valid tool to perform cell mobility studies such as migration studies in metastases or chemotaxis.

Pituitary adenomas are uncommon, difficult to diagnose tumors whose heterogeneity and low incidence complicate large-scale studies. The Molecular Registry of Pituitary Adenomas (REMAH) was promoted by the Andalusian Society of Endocrinology and Nutrition (SAEN) in 2008 as a cooperative clinical-basic multicenter strategy aimed at improving diagnosis and treatment of pituitary adenomas by combining clinical, pathological, and molecular information. In 2010, the Spanish Society of Endocrinology and Nutrition (SEEN) extended this project to national level and established 6 nodes with common protocols and methods for sample and clinical data collection, molecular analysis, and data recording in a common registry (www.remahnacional.com). The registry combines clinical data with molecular phenotyping of the resected pituitary adenoma using quantitative real-time PCR of expression of 26 genes: Pituitary hormones (GH-PRL-LH-FSH-PRL-ACTH-CGA), receptors (somatostatin, dopamine, GHRH, GnRH, CRH, arginine-vasopressin, ghrelin), other markers (Ki67, PTTG1), and control genes. Until 2015, molecular information has been collected from 704 adenomas, out of 1179 patients registered. This strategy allows for comparative and relational analysis between the molecular profile of the different types of adenoma and the clinical phenotype of patients, which may provide a better understanding of the condition and potentially help in treatment selection. The REMAH is therefore a unique multicenter, interdisciplinary network founded on a shared database that provides a far-reaching translational approach for management of pituitary adenomas, and paves the way for the conduct of combined clinical-basic innovative studies on large patient samples. (C) 2016 SEEN. Published by Elsevier Espana, S.L.U. All rights reserved.

[EN] This work aims to the estimation of fAPAR over the Iberian Peninsula using MODIS data. First, the 4SAIL2 and PROSPECT radiative transfer models have been used to simulate a data set of reflectance and fAPAR. Second, an artificial neuronal network (ANN) has been trained using the simulated data and finally, it has been inverted to derive fAPAR estimates over the Iberian Peninsula from MODIS reflectances images. Moreover, the impact that the observation and illumination configuration have on the fAPAR estimates has been assessed. The fAPAR estimates from MODIS have been compared with other validated fAPAR products. The results confirm an overall error around the user requirements (0.1) when the fAPAR estimated from the (PROSPECT+4SAIL2+Nadir) combination is compared with the selected products. This combination is proposed as an alternative to estimate fAPAR over the Iberian Peninsula due to the ability to characterize different land cover types as well as the high intra-annual variability of particular canopies, [ES] El objetivo de este trabajo consiste en la estimación de la fAPAR en la Península Ibérica a partir de datos MODIS. En primer lugar, se ha simulado un conjunto de datos de reflectividades y de fAPAR a partir de los modelos de transferencia radiativa de hoja (PROSPECT) y de cubiertas heterogéneas (4SAIL2). En segundo lugar, se ha entrenado un conjunto de redes neuronales artificiales (RNAs) para obtener mediante inversión la relación entre la fAPAR y las reflectividades simuladas y así calcular, por último, la fAPAR de la Península Ibérica a partir de imágenes de reflectivi-dad de MODIS. Además, se ha analizado la influencia de la configuración de observación e iluminación, nadir y oblicua. La fAPAR estimada se ha comparado con otros productos ya validados. Los resultados ponen de manifiesto que la fAPAR estimada a partir de la combinación (PROSPECT+4SAIL2+Nadir) proporciona, en general, diferencias alrededor del umbral requerido por los usuarios (0,1). Esta combinación se plantea como una alternativa para estimar la fAPAR en la Península Ibérica por su capacidad para caracterizar distintos tipos de cubiertas, así como por la alta variabilidad intra-anual observada en algunos casos, Este trabajo ha sido financiado por los proyectos ARTEMIS (CGL2008–00381), RESET CLIMATE (CGL2012–35831) y LSA SAF de Eumetsat. Los autores agradecen los comentarios de los revisores que han ayudado a mejorar significativamente el trabajo. Los productos MCD43A1, MCD43A2 y MOD17A2 han sido proporcionadas por el centro de datos Data Pool at the NASA Land Processes Distributed Active Archive Center (LP DAAC), USGS/Earth Resources Observation and Science (EROS) Center, Sioux Falls, South Dakota.

Póster elaborado para el WCRP Open Science Conference celebrado en Denver del 24 al 28 de octubre de 2011

Ponencia presentada en: XIII Congreso de la Asociación Española de Teledetección celebrado en Calatayud del 23 al 26 septiembre 2009. [ES]El objetivo principal del proyecto DULCINEA ha sido el desarrollo de una metodología multi-sensor para estimar parámetros biofísicos de la cubierta vegetal. La metodología desarrollada ha proporcionado estimaciones precisas de variables biofísicas de la vegetación (FVC, LAI) que han mostrado ser adecuadas para observar las variaciones inter- e intra-anuales de la cubierta en la Península Ibérica durante un periodo de 9 años (2000-2008). Los parámetros biofísicos obtenidos han permitido evaluar la vulnerabilidad de la vegetación ante condiciones ambientales extremas a nivel de la Península Ibérica. Un paso previo ha consistido en la elaboración de mapas detallados de parámetros climáticos y tipos de cubierta dominantes en la zona. Los modelos estadísticos aplicados han evidenciado una correlación significativa entre las variables biofísicas extraídas y algunas variables meteorológicas e índices de sequía operacionales. Esta interrelación es muy dependiente del tipo de cubierta y de las características climáticas de cada región. Se han encontrado correlaciones entre las anomalías de la cobertura vegetal y el SPI especialmente significativas para el caso de las regiones más secas, con valores típicos de R2 entre 0.4 y 0.7 durante los meses de Mayo y Junio. [EN]The main objective of the DULCINEA project is to provide coherent estimates of bio-physical variables such as fractional vegetation cover (FVC) and leaf area index (LAI) at regional to global scales. One of the goals of the project is to assess the potential of derived biophysical variables in the field of drought conditions monitoring. The aim was to analyse the vulnerability of natural ecosystems against the effects of climate fluctuations like drought and extreme events in the Iberian Peninsula, from the inter-correlation between the retrieved parameters and drought indices such as the Standardized Precipitation Index (SPI). The climatic disturbances affected both the growing season and the total amount of vegetation. Strong correlations have been found between SPI and satellitederived vegetation products, which are particularly significant in semi-arid regions. Este trabajo se enmarca en el proyecto DULCINEA (CGL2005-04202) y ha contado además con el soporte del proyecto ÁRTEMIS (CGL2008-00381).

Fatty acid hydroperoxide lyase (HPO-lyase) was purified 300-fold from tomatoes. The enzymatic activity appeared to be very unstable, but addition of Triton X100 and beta-mercaptoethanol to the buffer yielded an active enzyme that could be stored for several months at −80°C. The enzyme was inhibited by desferoxamine mesylate (desferal), 2-methyl-1,2-di-3-pyridyl-1-propanone (metyrapone), nordihydroguaiaretic acid (NDGA), n-propyl gallate and butylated hydroxyanisole, suggesting the involvement of free radicals in the reaction mechanism and the existence of a prosthetic group in the active center. However, no heme group could be demonstrated with the methods commonly used to identify heme groups in proteins. Only 13-hydroperoxides from linoleic acid (13-HPOD) and alpha-linolenic acid (alpha-13-HPOT) were cleaved by the tomato enzyme, with a clear preference for the latter substrate. The pH-optimum was 6.5, and for concentrations lower than 300 mu M a typical Michaelis–Menten curve was found with a Km of 77 mu M. At higher alpha-13-HPOT concentrations inhibition of the enzyme was observed, which could (at least in part) be attributed to 2E-hexenal. A curve of the substrate conversion as a function of the enzyme concentration revealed that 1 nkat of enzyme activity converts 0.7 mu mol alpha-13-HPOT before inactivation. Headspace analysis showed that tomato HPO-lyase formed hexanal from 13-HPOD and 3Z-hexenal from alpha-13-HPOT. A trace of the latter compound was isomerized to 2E-hexenal. In addition to the aldehydes, 12-oxo-9Z-dodecenoic acid was found by GC/MS analysis. To a small extent, isomerization to 12-oxo-10E-dodecenoic acid occurred.

10 pages, 1 figure, 5 tables.-- Online version published Apr. 2002., This paper reports a quantitative study of the effect of ring substituents in the 1-position of the aromatic ring on the rate of monophenol hydroxylation and o-diphenol oxidation catalyzed by tyrosinase. A possible correlation between the electron density of the carbon atom supporting the oxygen from the monophenolic hydroxyl group and the V Mmax values for each monophenol was found. In the case of o-diphenols the same effect was observed but the size of the side-chain became very important. NMR studies on the monophenols justified the sequence of the V Mmax values obtained. As regards the o-diphenols, on the other hand, only a fair correlation between NMR and V Dmax values was observed due to the effect of the molecular size of the ring substituent. From these data, it can be concluded that the redox step (k33) is not the rate-determining step of the reaction mechanism. Thus, the monophenols are converted into diphenols, but the order of specificities towards monophenols is different to that of o-diphenols. The rate-limiting step of the monophenolase activity could be the nucleophilic attack (k51) of the oxygen atom of the hydroxyl group on the copper atoms of the active site of the enzyme. This step could also be similar to or have a lower rate of attack than the electrophilic attack (k52) of the oxygen atom of the active site of oxytyrosinase on the C-3 of the monophenolic ring. However, the rate-limiting step in the diphenolase activity of tyrosinase could be related to both the nucleophilic power of the oxygen atom belonging to the hydroxyl group at the carbon atom in the 3-position (k32) and to the size of the substituent side-chain. On the basis of the results obtained, kinetic and structural models describing the monophenolase and diphenolase reaction mechanisms for tyrosinase are proposed., This paper was partially supported by the `Comisión Interministerial de Ciencia y Tecnología', project number CICYT PB98-0403-CO2. J. C. E. has a fellowship from the Programa Nacional de Formación del Personal Investigador, Ministerio de Educación y Ciencia (Spain), reference AP93 34785457.

Outcomes research; Risk factors Investigación de resultados; Factores de riesgo Recerca dels resultats; Factors de risc Bioprosthetic heart valves (BHVs) are commonly used to replace severely diseased heart valves but their susceptibility to structural valve degeneration (SVD) limits their use in young patients. We hypothesized that antibodies against immunogenic glycans present on BHVs, particularly antibodies against the xenoantigens galactose-α1,3-galactose (αGal) and N-glycolylneuraminic acid (Neu5Gc), could mediate their deterioration through calcification. We established a large longitudinal prospective international cohort of patients (n = 1668, 34 ± 43 months of follow-up (0.1–182); 4,998 blood samples) to investigate the hemodynamics and immune responses associated with BHVs up to 15 years after aortic valve replacement. Early signs of SVD appeared in