Circulating miRNAs as predictive biomarkers of type 2 diabetes mellitus development in coronary heart disease patients fromt he CORDIOPREV study

Circulating microRNAs (miRNAs) have been proposed as type 2 diabetes biomarkers, and they may be a more sensitive way to predict development of the disease than the currently used tools. Our aim was to identify whether circulating miRNAs, added to clinical and biochemical markers, yielded better potential for predicting type 2 diabetes. The study included 462 non-diabetic patients at baseline in the CORDIOPREV study. After a median follow-up of 60 months, 107 of them developed type 2 diabetes. Plasma levels of 24 miRNAs were measured at baseline by qRT-PCR, and other strong biomarkers to predict diabetes were determined. The ROC analysis identified 9 miRNAs, which, added to HbA1c, have a greater predictive value in early diagnosis of type 2 diabetes (AUC = 0.8342) than HbA1c alone (AUC = 0.6950). The miRNA and HbA1cbased model did not improve when the FINDRISC was included (AUC = 0.8293). Cox regression analyses showed that patients with low miR-103, miR-28-3p, miR-29a, and miR-9 and high miR-30a-5p and miR-150 circulating levels have a higher risk of disease (HR = 11.27; 95% CI = 2.61–48.65). Our results suggest that circulating miRNAs could potentially be used as a new tool for predicting the development of type 2 diabetes in clinical practice

Campus Accesible, Campus Igualitario

La Red de Investigación en Docencia Universitaria “Campus Accesible, Campus Igualitario”, vinculada al proyecto institucional del mismo nombre del Vicerrectorado de Campus y Sostenibilidad, la Unidad de Igualdad y el Vicerrectorado de Estudiantes, lleva funcionando tres cursos académicos, siendo el presente 2015-2016 el último de un ciclo, pues en la Universidad de Alicante ha habido elecciones rectorales y, por tanto, cambios en el equipo y en la estructura de su gobierno, y, además, la mayoría de los y las estudiantes que la componen están desarrollando su Proyecto Fin de Carrera en la Titulación de Arquitectura (Plan 1996), con lo que, pronto, serán profesionales y cerrarán una etapa de su vida. Conscientes de esta situación, que constituye un punto de inflexión en la Red, emprendimos nuestro trabajo con un triple objetivo: por un lado, visibilizar y difundir lo ya hecho en ediciones anteriores; por otro, hacer el sondeo de opinión sobre la práctica de deportes y actividades físicas en el Campus de la UA y el correspondiente estudio e informe; y, finalmente, culminar los talleres de diagnóstico, desde el punto de vista de la accesibilidad y la igualdad, de los espacios de la UA acometiendo un reconocimiento integral de su Campus

Mens sana in corpore sano: vivir y disfrutar el Campus de la Universidad de Alicante

Desde tiempos ancestrales, el ejercicio intelectual estuvo vinculado de forma natural a la práctica de la actividad, si no deportiva, al menos física. Pensar induce a discurrir y discurrir favorece pensar. Ese ejercicio físico que cuida y cultiva la salud de nuestro cuerpo, gentil continente de nuestros pensamientos y sentimientos, se halla a sus anchas cuando puede realizarse en un entorno que favorezca un cierto aislamiento de los ruidos del mundo y, además, un contacto íntimo con la naturaleza. Esta situación ideal es la que se da en el Campus de la Universidad de Alicante, espacio para la vida de la comunidad universitaria y, por tanto, para el ejercicio físico y mental. El presente trabajo aborda un análisis del contorno del mismo para poder correrlo y recorrerlo en su perímetro sin trabas a la accesibilidad y a la igualdad. De manera que un anillo peatonal inclusivo sea posible como réplica a la circulación rodada y así poder conquistar la ciudad paseable. Una ciudad, en nuestro caso universitaria, que recupera y completa los espacios públicos de relación y disfrute para el peatón. Las propuestas para su consecución constituyen, además de la posibilidad real de materializarlas, una práctica modélica para nuestro alumnado

Campus Accesible, Campus Igualitario

La Red de Investigación en Docencia Universitaria “Campus Accesible, Campus Igualitario”, vinculada al proyecto institucional del mismo nombre del Vicerrectorado de Campus y Sostenibilidad, la Unidad de Igualdad y el Vicerrectorado de Estudiantes, lleva funcionando tres cursos académicos, siendo el presente 2015-2016 el último de un ciclo, pues en la Universidad de Alicante ha habido elecciones rectorales y, por tanto, cambios en el equipo y en la estructura de su gobierno, y, además, la mayoría de los y las estudiantes que la componen están desarrollando su Proyecto Fin de Carrera en la Titulación de Arquitectura (Plan 1996), con lo que, pronto, serán profesionales y cerrarán una etapa de su vida. Conscientes de esta situación, que constituye un punto de inflexión en la Red, emprendimos nuestro trabajo con un triple objetivo: por un lado, visibilizar y difundir lo ya hecho en ediciones anteriores; por otro, hacer el sondeo de opinión sobre la práctica de deportes y actividades físicas en el Campus de la UA y el correspondiente estudio e informe; y, finalmente, culminar los talleres de diagnóstico, desde el punto de vista de la accesibilidad y la igualdad, de los espacios de la UA acometiendo un reconocimiento integral de su Campus

Campus Accesible para todas y todos

El RD 1393/2007 por el que se establece la ordenación de las enseñanzas universitarias, indica que la formación en cualquier actividad profesional debe contribuir al conocimiento y desarrollo de los principios de accesibilidad universal, diseño para todos/as, igualdad entre hombres y mujeres y la protección del medioambiente. Atendiendo a estas necesidades formativas que deben ser recogidas en los títulos de grado, desde la Universidad de Alicante y su Vicerrectorado de Campus y Sostenibilidad, se lleva a cabo el “Plan de Movilidad Sostenible” y el proyecto “Campus Accesible, Campus Igualitario”, potenciándose la adquisición de competencias sobre accesibilidad universal. El objetivo es exponer la metodología seguida para reforzar el proceso de adquisición de competencias emprendedoras, permitiendo tener un campus accesible, desarrollando un espíritu crítico y aportando ideas que mejoren la accesibilidad a la sociedad y en concreto a la comunidad universitaria. Se expone la metodología a seguir que consiste en una fase de elaboración de fichas técnicas, una segunda fase de toma de datos, una tercera fase de análisis de resultados y, finalmente unas propuestas de mejora. La adquisición de competencias van a permitir que nuestros/as estudiantes, una vez finalicen sus estudios, puedan aplicar estos conocimientos integradores allá donde desarrollen su profesión

Multicentre, randomised, single-blind, parallel group trial to compare the effectiveness of a Holter for Parkinson's symptoms against other clinical monitoring methods: study protocol

Introduction In recent years, multiple studies have aimed to develop and validate portable technological devices capable of monitoring the motor complications of Parkinson's disease patients (Parkinson's Holter). The effectiveness of these monitoring devices for improving clinical control is not known. Methods and analysis This is a single-blind, cluster-randomised controlled clinical trial. Neurologists from Spanish health centres will be randomly assigned to one of three study arms (1:1:1): (a) therapeutic adjustment using information from a Parkinson?s Holter that will be worn by their patients for 7 days, (b) therapeutic adjustment using information from a diary of motor fluctuations that will be completed by their patients for 7 days and (c) therapeutic adjustment using clinical information collected during consultation. It is expected that 162 consecutive patients will be included over a period of 6 months. The primary outcome is the efficiency of the Parkinson?s Holter compared with traditional clinical practice in terms of Off time reduction with respect to the baseline (recorded through a diary of motor fluctuations, which will be completed by all patients). As secondary outcomes, changes in variables related to other motor complications (dyskinesia and freezing of gait), quality of life, autonomy in activities of daily living, adherence to the monitoring system and number of doctor?patient contacts will be analysed. The noninferiority of the Parkinson's Holter against the diary of motor fluctuations in terms of Off time reduction will be studied as the exploratory objective. Ethics and dissemination approval for this study has been obtained from the Hospital Universitari de Bellvitge Ethics Committee. The results of this study will inform the practical utility of the objective information provided by a Parkinson's Holter and, therefore, the convenience of adopting this technology in clinical practice and in future clinical trials. We expect public dissemination of the results in 2022.Funding This work is supported by AbbVie S.L.U, the Instituto de Salud Carlos III [DTS17/00195] and the European Fund for Regional Development, 'A way to make Europe'

Feline Leukemia Virus and Other Pathogens as Important Threats to the Survival of the Critically Endangered Iberian Lynx (Lynx pardinus)

BACKGROUND: The Iberian lynx (Lynx pardinus) is considered the most endangered felid species in the world. In order to save this species, the Spanish authorities implemented a captive breeding program recruiting lynxes from the wild. In this context, a retrospective survey on prevalence of selected feline pathogens in free-ranging lynxes was initiated. METHODOLOGY/ PRINCIPAL FINDINGS: We systematically analyzed the prevalence and importance of seven viral, one protozoan (Cytauxzoon felis), and several bacterial (e.g., hemotropic mycoplasma) infections in 77 of approximately 200 remaining free-ranging Iberian lynxes of the Doñana and Sierra Morena areas, in Southern Spain, between 2003 and 2007. With the exception of feline immunodeficiency virus (FIV), evidence of infection by all tested feline pathogens was found in Iberian lynxes. Fourteen lynxes were feline leukemia virus (FeLV) provirus-positive; eleven of these were antigenemic (FeLV p27 positive). All 14 animals tested negative for other viral infections. During a six-month period in 2007, six of the provirus-positive antigenemic lynxes died. Infection with FeLV but not with other infectious agents was associated with mortality (p<0.001). Sequencing of the FeLV surface glycoprotein gene revealed a common origin for ten of the eleven samples. The ten sequences were closely related to FeLV-A/61E, originally isolated from cats in the USA. Endogenous FeLV sequences were not detected. CONCLUSIONS/SIGNIFICANCE: It was concluded that the FeLV infection most likely originated from domestic cats invading the lynx's habitats. Data available regarding the time frame, co-infections, and outcome of FeLV-infections suggest that, in contrast to the domestic cat, the FeLV strain affecting the lynxes in 2007 is highly virulent to this species. Our data argue strongly for vaccination of lynxes and domestic cats in and around lynx's habitats in order to prevent further spread of the virus as well as reduction the domestic cat population if the lynx population is to be maintained

Regulatory sites for splicing in human basal ganglia are enriched for disease-relevant information

Genome-wide association studies have generated an increasing number of common genetic variants associated with neurological and psychiatric disease risk. An improved understanding of the genetic control of gene expression in human brain is vital considering this is the likely modus operandum for many causal variants. However, human brain sampling complexities limit the explanatory power of brain-related expression quantitative trait loci (eQTL) and allele-specific expression (ASE) signals. We address this, using paired genomic and transcriptomic data from putamen and substantia nigra from 117 human brains, interrogating regulation at different RNA processing stages and uncovering novel transcripts. We identify disease-relevant regulatory loci, find that splicing eQTLs are enriched for regulatory information of neuron-specific genes, that ASEs provide cell-specific regulatory information with evidence for cellular specificity, and that incomplete annotation of the brain transcriptome limits interpretation of risk loci for neuropsychiatric disease. This resource of regulatory data is accessible through our web server, http://braineacv2.inf.um.es/

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease

Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies

Background Genome-wide association studies (GWAS) in Parkinson's disease have increased the scope of biological knowledge about the disease over the past decade. We aimed to use the largest aggregate of GWAS data to identify novel risk loci and gain further insight into the causes of Parkinson's disease. Methods We did a meta-analysis of 17 datasets from Parkinson's disease GWAS available from European ancestry samples to nominate novel loci for disease risk. These datasets incorporated all available data. We then used these data to estimate heritable risk and develop predictive models of this heritability. We also used large gene expression and methylation resources to examine possible functional consequences as well as tissue, cell type, and biological pathway enrichments for the identified risk factors. Additionally, we examined shared genetic risk between Parkinson's disease and other phenotypes of interest via genetic correlations followed by Mendelian randomisation. Findings Between Oct 1, 2017, and Aug 9, 2018, we analysed 7·8 million single nucleotide polymorphisms in 37 688 cases, 18 618 UK Biobank proxy-cases (ie, individuals who do not have Parkinson's disease but have a first degree relative that does), and 1·4 million controls. We identified 90 independent genome-wide significant risk signals across 78 genomic regions, including 38 novel independent risk signals in 37 loci. These 90 variants explained 16–36% of the heritable risk of Parkinson's disease depending on prevalence. Integrating methylation and expression data within a Mendelian randomisation framework identified putatively associated genes at 70 risk signals underlying GWAS loci for follow-up functional studies. Tissue-specific expression enrichment analyses suggested Parkinson's disease loci were heavily brain-enriched, with specific neuronal cell types being implicated from single cell data. We found significant genetic correlations with brain volumes (false discovery rate-adjusted p=0·0035 for intracranial volume, p=0·024 for putamen volume), smoking status (p=0·024), and educational attainment (p=0·038). Mendelian randomisation between cognitive performance and Parkinson's disease risk showed a robust association (p=8·00 × 10−7). Interpretation These data provide the most comprehensive survey of genetic risk within Parkinson's disease to date, to the best of our knowledge, by revealing many additional Parkinson's disease risk loci, providing a biological context for these risk factors, and showing that a considerable genetic component of this disease remains unidentified. These associations derived from European ancestry datasets will need to be followed-up with more diverse data. Funding The National Institute on Aging at the National Institutes of Health (USA), The Michael J Fox Foundation, and The Parkinson's Foundation (see appendix for full list of funding sources)