The object in dust jackets by Daniel Gil: artistic influence on the conceptualization of the graphic image in his book covers

Reseña de tesis doctora

Interdisciplinary Tutoring for the Development of Professional-Simulation Role-Plays

Current society is characterised by a growing tendency of interrelationship among different professional sectors in order to offer their potential customers a better quality of certain products or process. Thereby, and in the context of this interdisciplinarity, higher-education teachers must frame their teaching methodologies mainly focused on the acquisition of certain competences so that students could guarantee the development of their professional abilities. Taking this as a premise, we have performed an interdisciplinary role-play so as to allow our students to acquire those professional competences. However, to carry out this performance a well-organised tutorial plan, divided into several tutoring sessions, was required to succeed in the use of this active methodology

Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications

ESRETNET Study Group, The ERDC Study Group, The Associated Clinical Study Group.Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations.This work was supported by the Instituto de Salud Carlos III (ISCIII) of the Spanish Ministry of Health (FIS; PI16/00425 and PI19/00321), Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER, 06/07/0036), IIS-FJD BioBank (PT13/0010/0012), Comunidad de Madrid (CAM, RAREGenomics Project, B2017/BMD-3721), European Regional Development Fund (FEDER), the Organización Nacional de Ciegos Españoles (ONCE), Fundación Ramón Areces, Fundación Conchita Rábago and the University Chair UAM-IIS-FJD of Genomic Medicine. Irene Perea-Romero is supported by a PhD fellowship from the predoctoral Program from ISCIII (FI17/00192). Ionut F. Iancu is supported by a grant from the Comunidad de Madrid (CAM, PEJ-2017-AI/BMD7256). Marta del Pozo-Valero is supported by a PhD grant from the Fundación Conchita Rábago. Berta Almoguera is supported by a Juan Rodes program from ISCIII (JR17/00020). Pablo Minguez is supported by a Miguel Servet program from ISCIII (CP16/00116). Marta Corton is supported by a Miguel Servet program from ISCIII (CPII17/00006)

Abordaje del paciente hiperfrecuentador de servicios en atención primaria: un acercamiento desde la teoría

Este artículo hace una revisión de la literatura sobre la hiperfrecuentación de servicios de salud, con el objetivo de analizar la magnitud del problema para para el paciente, las familias y el sistema de salud, así como sus posibles factores asociados. Se realizó una búsqueda en revistas nacionales e internacionales para proponer una definición que permita estandarizar criterios para su detección, así como analizar posibles factores que puedan generar o perpetuar dicha conducta en el contexto nacional, con base en el modelo teórico de Aday y Andersen. También se sugieren algunas estrategias de intervención en servicios de baja complejidad. Se propone el uso de percentiles en la definición de los casos y a los trastornos mentales comunes como posibles contribuyentes de este comportamiento en salud. Con este artículo se espera contribuir a la generación de conocimiento del uso de servicios cuando las barreras de acceso han sido superadas

Los ojos de Daniel Gil: la cubierta del libro un espacio preferente para el diseñador

In the practice of editorial design, book cover represents the viewer's first visual contact with the product. Hence, in its creation process it is given space and time to determine the formal and aesthetic aspects that will determine its character. In some cases this character will be purely functional while in others it will have more subjective characteristics. This will depend on the designer's own stance towards the concept of design. From our point of view, we understand that such responsibility entails understanding design as a creative project that integrates creative freedom and the functionality of the objective itself, bearing in mind as a maxim the involvement of design in social and cultural communication.En la práctica del diseño editorial la cubierta del libro representa el primer contacto visual del espectador con el producto. De ahí que en su proceso de creación se le conceda espacio y tiempo a la hora de determinar los aspectos formales y estéticos que determinarán su carácter. En algunos casos este carácter será puramente funcional mientras que en otros presentará características más subjetivas. Ello dependerá de la postura del propio diseñador frente al concepto de diseño.Desde nuestro punto de vista entendemos que tal responsabilidad conlleva entender el diseño como proyecto creativo que integra la libertad creadora y la funcionalidad del propio objetivo, teniendo presente como máxima la implicación del diseño en la comunicación social y cultural

Comparative structural analysis of the drought responsive dehydrin and aquaporin gene families in Brachypodium and close grasses

Dehydrins (DHNs) belong to the group 2 LEA (Late Embryogenesis Abundant) genes and play an important role in the response of plants to abiotic stress, mainly heat, salinity and drought. Under these stresses, DHNs accumulate to a large extent in maturing seeds and in all vegetative tissues. As many studies reveal, there is a positive correlation between DHN gene expression (synthesis of DHN proteins) and plant stress tolerance. Aquaporins (AQPs) belong to the major intrinsic protein (MIP) superfamily of membrane proteins conserved in plants and animals as well as in bacteria. Supporting evidence suggests that AQPs have an important role in stomatal closure and circadian regulation. There are more than 150 MIPs identified and, although some of them are constitutively expressed, others are regulated in response to drought and salinity. In this study, sequence and annotation data has been retrieved from Phytozome and Ensembl Plants in order to compare DHNs and AQPs in four Brachypodium species, 54 B. distachyon varieties and five cereals (Zea mays, Sorghum bicolor, Oryza sativa, Hordeum vulgare and Triticum aestivum). In the B. distachyon intra-species comparison, drought tolerant lines seem to contain slightly lower numbers of aquaporin and dehydrin genes, they are shorter, and some of them are dissimilar to those of the rest. The physical distribution of AQPs includes a cluster of genes that splits the lines into two main groups depending on its location, either in chromosome 3 or in chromosome 4 of this species. However, this does not seem to be related to drought stress susceptibility.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Diacylglycerol kinase ζ limits IL-2-dependent control of PD-1 expression in tumor-infiltrating T lymphocytes

Background The inhibitory functions triggered by the programmed cell death-1 (PD-1) receptor following binding to its ligand (PD-L1) protect healthy organs from cytotoxic T cells, and neutralize antitumor T cell attack. Antibody-based therapies to block PD-1/PD-L1 interaction have yielded notable results, but most patients eventually develop resistance. This failure is attributed to CD8+ T cells achieving hyporesponsive states from which recovery is hardly feasible. Dysfunctional T cell phenotypes are favored by a sustained imbalance in the diacylglycerol (DAG)- and Ca2+-regulated transcriptional programs. In mice, DAG kinase ζ (DGKζ) facilitates DAG consumption, limiting T cell activation and cytotoxic T cell responses. DGKζ deficiency facilitates tumor rejection in mice without apparent adverse autoimmune effects. Despite its therapeutic potential, little is known about DGKζ function in human T cells, and no known inhibitors target this isoform.Methods We used a human triple parameter reporter cell line to examine the consequences of DGKζ depletion on the transcriptional restriction imposed by PD-1 ligation. We studied the effect of DGKζ deficiency on PD-1 expression dynamics, as well as the impact of DGKζ absence on the in vivo growth of MC38 adenocarcinoma cells.Results We demonstrate that DGKζ depletion enhances DAG-regulated transcriptional programs, promoting interleukin-2 production and partially counteracting PD-1 inhibitory functions. DGKζ loss results in limited PD-1 expression and enhanced expansion of cytotoxic CD8+ T cell populations. This is observed even in immunosuppressive milieus, and correlates with the reduced ability of MC38 adenocarcinoma cells to form tumors in DGKζ-deficient mice.Conclusions Our results, which define a role for DGKζ in the control of PD-1 expression, confirm DGKζ potential as a therapeutic target as well as a biomarker of CD8+ T cell dysfunctional states