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Wai T.,University of Cologne | Wai T.,Max Planck Institute for Biology of Ageing | Baker M.J.,University of Cologne | Merkwirth C.,University of Cologne | And 9 more authors.
Science | Year: 2015

Mitochondrial morphology is shaped by fusion and division of their membranes. Here, we found that adultmyocardial function depends on balanced mitochondrial fusion and fission, maintained by processing of the dynamin-like guanosine triphosphatase OPA1 by the mitochondrial peptidases YME1L and OMA1. Cardiac-specific ablation of Yme1l in mice activated OMA1 and accelerated OPA1 proteolysis, which triggered mitochondrial fragmentation and altered cardiac metabolism.This caused dilated cardiomyopathy and heart failure. Cardiac function and mitochondrial morphology were rescued by Oma1 deletion, which prevented OPA1 cleavage. Feedingmice a high-fat diet or ablating Yme1l in skeletal muscle restored cardiacmetabolism and preserved heart function without suppressing mitochondrial fragmentation. Thus, unprocessed OPA1 is sufficient tomaintain heart function,OMA1 is a critical regulator of cardiomyocyte survival, and mitochondrial morphology and cardiac metabolism are intimately linked.

Breso A.,Polytechnic University of Valencia | Martinez-Miranda J.,CICESE | Fuster-Garcia E.,Polytechnic University of Valencia | Fuster-Garcia E.,VeraTech for Health | And 3 more authors.
International Journal of Human Computer Studies | Year: 2016

Human Computer Interaction (HCI) is a research field which aims to improve the relationship between users and interactive computer systems. A main objective of this research area is to make the user experience more pleasant and efficient, minimizing the barrier between the users cognition of what they want to accomplish and the computers understanding of the users tasks, by means of user-friendly, useful and usable designs. A bad HCI design is one of the main reasons behind user rejection of computer-based applications, which in turn produces loss of productivity and economy in industrial environments. In the eHealth domain, user rejection of computer-based systems is a major barrier to exploiting the maximum benefit from those applications developed to support the treatment of diseases, and in the worst cases a poor design in these systems may cause deterioration in the clinical condition of the patient. Thus, a high level of personalisation of the system according to users needs is extremely important, making it easy to use and contributing to the systems efficacy, which in turn facilitates the empowerment of the target users. Ideally, the content offered through the interactive sessions in these applications should be continuously assessed and adapted to the changing condition of the patient. A good HCI design and development can improve the acceptance of these applications and contribute to promoting better adherence levels to the treatment, preventing the patient from further relapses. In this work, we present a mechanism to provide personalised and adaptive daily interactive sessions focused on the treatment of patients with Major Depression. These sessions are able to automatically adapt the content and length of the sessions to obtain personalised and varied sessions in order to encourage the continuous and long-term use of the system. The tailored adaptation of session content is supported by decision-making processes based on: (i) clinical requirements; (ii) the patient's historical data; and (iii) current responses from the patient. We have evaluated our system through two different methodologies: the first one performing a set of simulations producing different sessions from changing input conditions, in order to assess different levels of adaptability and variability of the session content offered by the system. The second evaluation process involved a set of patients who used the system for 14-28 days and answered a questionnaire to provide feedback about the perceived level of adaptability and variability produced by the system. The obtained results in both evaluations indicated good levels of adaptability and variability in the content of the sessions according to the input conditions. © 2015 Elsevier Ltd.

Blasco-Fontecilla H.,Hospital Universitario Puerta Of Hierro | Blasco-Fontecilla H.,Research Center Biomedica En Red Of Salud Mental Cibersam | Blasco-Fontecilla H.,Autonomous University of Madrid | Gonzalez-Perez M.,Hospital Universitario Puerta Of Hierro | And 5 more authors.
Revista de Psiquiatria y Salud Mental | Year: 2016

Objective To examine the effectiveness of playing chess as a treatment option for children with ADHD. Methods Parents of 44 children ages 6 to 17 with a primary diagnosis of ADHD consented to take part in the study. Parents completed the Spanish version of the Swanson, Nolan and Pelham Scale for parents (SNAP-IV) and the Abbreviated Conner's Rating Scales for parents (CPRS-HI) prior to an 11-week chess-training program. We used a paired t-test to compare pre- and post-intervention outcomes, and Cohen-d calculations to measure the magnitude of the effect. The statistical significance was set at P <.05. Results Children with ADHD improved in both the SNAP-IV (t = 6.23; degrees of freedom (df) = 41; P <.001) and the CPRS-HI (t = 5.39; df = 33; P <.001). Our results suggest a large effect in decreasing the severity of ADHD as measured by the SNAP-IV (d = 0.85) and the CPRS-HI (d = 0.85). Furthermore, we found a correlation between intelligence quotient and SNAP-IV improvement (P <.05). Conclusions The results of our pilot study should be interpreted with caution. This pilot project highlights the importance of carrying out larger studies with a case-control design. If our results are replicated in better designed studies, playing chess could be included within the multimodal treatment of ADHD. © 2014 SEP y SEPB.

Salinas A.J.,Complutense University of Madrid | Salinas A.J.,CIBER ISCIII | Esbrit P.,Institute Investigacion Sanitaria IIS | Esbrit P.,Institute Salud Carlos III | And 2 more authors.
Biomaterials Science | Year: 2013

Biomimetics takes advantage of natural strategies for the solution of technological problems, including the proper design of biomaterials. Living bone exhibits a hierarchical porosity with both giant and nanometric pores which must be reproduced for the design of biomaterials for hard tissue repair. Bioactive and degradable bioceramics are a good alternative for the manufacture of scaffolds. Tissue engineering approaches to improve bone regeneration include strategies supporting endogenous osteoblast adhesion, proliferation (osteoconduction), osteoinduction by growth factors, and osteoprogenitors. Understanding the natural ossification mechanisms and the role of biomolecules involved in this process is a requirement for the design of bone tissue scaffolds. Mesoporous bioactive ceramics, namely mesoporous silica and templated glasses with nanometric pores to host growth factors, conformed into 3D scaffolds with micrometric porosity by rapid prototyping, are a good option for bone regeneration. In this regard, biomolecules such as well characterized bone morphogenetic proteins and others under current research, such as osteostatin and osteoprogenitors, are promising strategies in bone tissue engineering applications. Future developments in biomaterials will come in both micro- and nano- scales, and molecular and cell biology approaches will provide suitable solutions to the demanding needs of these compounds. © 2013 The Royal Society of Chemistry.

Esbrit P.,Institute Investigacion Sanitaria IIS | Esbrit P.,Institute Salud Carlos III | Alcaraz M.J.,Institute Salud Carlos III | Alcaraz M.J.,University of Valencia
Biochemical Pharmacology | Year: 2013

Osteoporosis is characterized by low bone mineral density and/or poor bone microarchitecture leading to an increased risk of fractures. The skeletal alterations in osteoporosis are a consequence of a relative deficit of bone formation compared to bone resorption. Osteoporosis therapies have mostly relied on antiresorptive drugs. An alternative therapeutic approach for osteoporosis is currently available, based on the intermittent administration of parathyroid hormone (PTH). Bone anabolism caused by PTH therapy is mainly accounted for by the ability of PTH to increase osteoblastogenesis and osteoblast survival. PTH and PTH-related protein (PTHrP)-an abundant local factor in bone- interact with the common PTH type 1 receptor with similar affinities in osteoblasts. Studies mainly in osteoporosis rodent models and limited data in postmenopausal women suggest that N-terminal PTHrP peptides might be considered a promising bone anabolic therapy. In addition, putative osteogenic actions of PTHrP might be ascribed not only to its N-terminal domain but also to its PTH-unrelated C-terminal region. In this review, we discuss the underlying cellular and molecular mechanisms of the anabolic actions of PTH and the similar potential of PTH-related protein (PTHrP) to increase bone mass and improve bone regeneration. © 2013 Elsevier Inc. All rights reserved.

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