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Rigat-Brugarolas L.G.,Institute for Bioengineering of Catalonia IBEC | Rigat-Brugarolas L.G.,Research Center Biomedica En Red Of Bioingenieria | Homs-Corbera A.,Institute for Bioengineering of Catalonia IBEC | Homs-Corbera A.,Research Center Biomedica En Red Of Bioingenieria | And 3 more authors.
RSC Advances | Year: 2015

We present a novel methodology to create in a simple, fast and cheap way an interpenetrating polymer network biomaterial, mixing 2-hydroxyethil methacrylate and poly(dimethylsiloxane), for long-lasting highly hydrophilic microfluidic device prototyping. The presented polymer could be potentially useful to develop point-of-care microfluidic diagnostic devices allowing blood displacement without exertion in microchannels while proving to have low biological analytes adhesion. © 2015 The Royal Society of Chemistry. Source

Pueyo E.,University of Oxford | Pueyo E.,University of Zaragoza | Pueyo E.,Research Center Biomedica En Red Of Bioingenieria | Husti Z.,University of Szeged | And 8 more authors.
American Journal of Physiology - Heart and Circulatory Physiology | Year: 2010

Protracted QT interval (QTI) adaptation to abrupt heart rate (HR) changes has been identified as a clinical arrhythmic risk marker. This study investigates the ionic mechanisms of QTI rate adaptation and its relationship to arrhythmic risk. Computer simulations and experimental recordings in human and canine ventricular tissue were used to investigate the ionic basis of QTI and action potential duration (APD) to abrupt changes in HR with a protocol commonly used in clinical studies. The time for 90% QTI adaptation is 3.5 min in simulations, in agreement with experimental and clinical data in humans. APD adaptation follows similar dynamics, being faster in midmyocardial cells (2.5 min) than in endocardial and epicardial cells (3.5 min). Both QTI and APD adapt in two phases following an abrupt HR change: a fast initial phase with time constant < 30 s, mainly related to L-type calcium and slow-delayed rectifier potassium current, and a second slow phase of >2 min driven by intracellular sodium concentration ([Na+]i) dynamics. Alterations in [Na +]i dynamics due to Na+/K+ pump current inhibition result in protracted rate adaptation and are associated with increased proarrhythmic risk, as indicated by action potential triangulation and faster L-type calcium current recovery from inactivation, leading to the formation of early afterdepolarizations. In conclusion, this study suggests that protracted QTI adaptation could be an indicator of altered [Na+]i dynamics following Na+/K+ pump inhibition as it occurs in patients with ischemia or heart failure. An increased risk of cardiac arrhythmias in patients with protracted rate adaptation may be due to an increased risk of early afterdepolarization formation. Copyright © 2010 the American Physiological Society. Source

Rodriguez-Hernandez C.J.,Barcelona Institute for Research in Biomedicine | Rodriguez-Hernandez C.J.,Developmental Tumor Biology Laboratory | Llorens-Agost M.,Institute Biologia Molecular Y Celular Of Plantas Upv Csic | Llorens-Agost M.,National University of Ireland | And 6 more authors.
FEBS Letters | Year: 2013

Both radiotherapy and most effective chemotherapeutic agents induce different types of DNA damage. Here we show that tungstate modulates cell response to DNA damaging agents. Cells treated with tungstate were more sensitive to etoposide, phleomycin and ionizing radiation (IR), all of which induce DNA double-strand breaks (DSBs). Tungstate also modulated the activation of the central DSB signalling kinase, ATM, in response to these agents. These effects required the functionality of the Mre11-Nbs1-Rad50 (MRN) complex and were mimicked by the inhibition of PP2A phosphatase. Therefore, tungstate may have adjuvant activity when combined with DNA-damaging agents in the treatment of several malignancies. © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. Source

Llamedo M.,University of Buenos Aires | Llamedo M.,Aragon Institute of Engineering Research | Llamedo M.,Research Center Biomedica En Red Of Bioingenieria | Khawaja A.,Biosigna GmbH | And 2 more authors.
IEEE Transactions on Information Technology in Biomedicine | Year: 2012

In this paper, we studied the improvement in heartbeat classification achieved by including information from multilead ECG recordings in a previously developed and validated classification model. This model includes features from the RR interval series and morphology descriptors for each lead calculated from the wavelet transform. The experiments were carried out in the INCART database, available in Physionet, and the generalization was corroborated in private and public databases. In all databases, the AAMI recommendations for class labeling and results presentation were followed. Different strategies to integrate the additional information available in the 12-leads were studied. The best performing strategy consisted in performing principal component analysis to the wavelet transform of the available ECG leads. The performance indices obtained for normal beats were sensitivity ( S) 98%, positive predictive value ( P +) 93%; for supraventricular beats, ( S) 86%, (P + ) 91%; and for ventricular beats (S) 90%, (P +) 90%. The generalization capability of the chosen strategy was confirmed by applying the classifier to other databases with different number of leads with comparable results. In conclusion, the performance of the reference two-lead classifier was improved by taking into account additional information from the 12-leads. © 1997-2012 IEEE. Source

Navarro S.,CIEMAT | Navarro S.,CIBER ISCIII | Moleiro V.,CIEMAT | Moleiro V.,CIBER ISCIII | And 29 more authors.
Stem Cells | Year: 2014

Fanconi anemia (FA) is a complex genetic disease associated with a defective DNA repair pathway known as the FA pathway. In contrast to many other FA proteins, BRCA2 participates downstream in this pathway and has a critical role in homology-directed recombination (HDR). In our current studies, we have observed an extremely low reprogramming efficiency in cells with a hypomorphic mutation in Brca2 (Brca2Δ27/Δ27), that was associated with increased apoptosis and defective generation of nuclear RAD51 foci during the reprogramming process. Gene complementation facilitated the generation of Brca2Δ27/Δ27 induced pluripotent stem cells (iPSCs) with a disease-free FA phenotype. Karyotype analyses and comparative genome hybridization arrays of complemented Brca2Δ27/Δ27 iPSCs showed, however, the presence of different genetic alterations in these cells, most of which were not evident in their parental Brca2 Δ27/Δ27 mouse embryonic fibroblasts. Gene-corrected Brca2Δ27/Δ27 iPSCs could be differentiated in vitro toward the hematopoietic lineage, although with a more limited efficacy than WT iPSCs or mouse embryonic stem cells, and did not engraft in irradiated Brca2Δ27/Δ27 recipients. Our results are consistent with previous studies proposing that HDR is critical for cell reprogramming and demonstrate that reprogramming defects characteristic of Brca2 mutant cells can be efficiently overcome by gene complementation. Finally, based on analysis of the phenotype, genetic stability, and hematopoietic differentiation potential of gene-corrected Brca2Δ27/Δ27 iPSCs, achievements and limitations in the application of current reprogramming approaches in hematopoietic stem cell therapy are also discussed. © AlphaMed Press 2013. Source

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