CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

STK11 (LKB1) missense somatic mutant isoforms promote tumor growth, motility and inflammation

Genètica del càncer; Càncer de pulmó; OncògensGenética del cáncer; Cáncer de pulmón; OncogenesCancer genetics; Lung cancer; OncogenesElucidating the contribution of somatic mutations to cancer is essential for personalized medicine. STK11 (LKB1) appears to be inactivated in human cancer. However, somatic missense mutations also occur, and the role/s of these alterations to this disease remain unknown. Here, we investigated the contribution of four missense LKB1 somatic mutations in tumor biology. Three out of the four mutants lost their tumor suppressor capabilities and showed deficient kinase activity. The remaining mutant retained the enzymatic activity of wild type LKB1, but induced increased cell motility. Mechanistically, LKB1 mutants resulted in differential gene expression of genes encoding vesicle trafficking regulating molecules, adhesion molecules and cytokines. The differentially regulated genes correlated with protein networks identified through comparative secretome analysis. Notably, three mutant isoforms promoted tumor growth, and one induced inflammation-like features together with dysregulated levels of cytokines. These findings uncover oncogenic roles of LKB1 somatic mutations, and will aid in further understanding their contributions to cancer development and progression.This work was supported by funds from the Spanish Health Ministry (Fondo de Investigaciones Sanitarias-FIS) PI1400375-Fondos FEDER, PI17/00043-Fondos FEDER, Euronanomed2-ISCIII (AC16/00019)-Fondos FEDER, Asociación Española Contra el Cancer (AECC-GCB15152978SOEN) supported PGM, KM., Ramón Areces Foundation supported KM and research

Benefit of primary percutaneous coronary interventions in the elderly with ST segment elevation myocardial infarction

Objective: Primary percutaneous coronary intervention (P-PCI) has demonstrated its efficacy in patients with ST segment elevation myocardial infarction (STEMI). However, patients with STEMI ≥75 years receive less P-PCI than younger patients despite their higher in-hospital morbimortality. The objective of this analysis was to determine the effectiveness of P-PCI in patients with STEMI ≥75 years. Methods: We included 979 patients with STEMI ≥75 years, from the ATención HOspitalaria del Síndrome coronario study, a registry of 8142 consecutive patients with acute coronary syndrome admitted at 31 Spanish hospitals in 2014-2016. We calculated a propensity score (PS) for the indication of P-PCI. Patients that received or not P-PCI were matched by PS. Using logistic regression, we compared the effectiveness of performing P-PCI versus non-performance for the composite primary event, which included death, reinfarction, acute pulmonary oedema or cardiogenic shock during hospitalisation. Results: Of the included patients, 81.5 % received P-PCI. The matching provided two groups of 169 patients with and without P-PCI. Compared with its non-performance, P-PCI presented a composite event OR adjusted by PS of 0.55 (95% CI 0.34 to 0.89). Conclusions: Receiving a P-PCI was significantly associated with a reduced risk of major intrahospital complications in patients with STEMI aged 75 years or older

Benefit of primary percutaneous coronary interventions in the elderly with ST segment elevation myocardial infarction

Altres ajuts: Supported by: MARATO TV3 (081630); Red RedIAPP RD06/0018; CP12/03287; CIBER Epidemiología y Salud Pública; CIBERCV de enfermedades Cardiovasculares, Fondo Europeo de Desarrollo Regional (FEDER) (European Regional Development Funds -ERDF-); FIS CP12/03287, FIS 14/00449, FIS PI081327, FIS INTRASALUD PI1101801.Primary percutaneous coronary intervention (P-PCI) has demonstrated its efficacy in patients with ST segment elevation myocardial infarction (STEMI). However, patients with STEMI ≥75 years receive less P-PCI than younger patients despite their higher in-hospital morbimortality. The objective of this analysis was to determine the effectiveness of P-PCI in patients with STEMI ≥75 years. We included 979 patients with STEMI ≥75 years, from the ATención HOspitalaria del Síndrome coronario study, a registry of 8142 consecutive patients with acute coronary syndrome admitted at 31 Spanish hospitals in 2014-2016. We calculated a propensity score (PS) for the indication of P-PCI. Patients that received or not P-PCI were matched by PS. Using logistic regression, we compared the effectiveness of performing P-PCI versus non-performance for the composite primary event, which included death, reinfarction, acute pulmonary oedema or cardiogenic shock during hospitalisation. Of the included patients, 81.5 % received P-PCI. The matching provided two groups of 169 patients with and without P-PCI. Compared with its non-performance, P-PCI presented a composite event OR adjusted by PS of 0.55 (95% CI 0.34 to 0.89). Receiving a P-PCI was significantly associated with a reduced risk of major intrahospital complications in patients with STEMI aged 75 years or older

Forest tree genomics: 10 achievements from the past 10 years and future prospects

This review highlights some of the discoveries and applications made possible by “omics” technologies over the last 10 years and provides perspectives for pioneering research to increase our understanding of tree biology.ContextA decade after the first forest tree genome sequence was released into the public domain, the rapidly evolving genomics and bioinformatics toolbox has advanced our understanding of the structure, functioning, and evolution of forest tree genomes.Aims and methodsThis review highlights some of the discoveries and applications that “omics” technologies have made possible for forest trees over the past 10 years.ResultsIn this review, we start by our current understanding of genome evolution and intricacies of gene regulation for reproduction, development, and responses to biotic and abiotic stresses. We then skim over advances in interactome analysis and epigenomics, the knowledge of the extent of genetic variation within and between species, revealing micro- and macro-evolutionary processes and species history, together with the complex architecture of quantitative traits. We finally end with applications in genetic resource conservation and breeding.ConclusionThe knowledge gained through the use of these technologies has a huge potential impact for adapting forests to the main challenges they will have to face: changing demand from ecosystem services with potentially conflicting strategies in terms of conservation and use, as well as climate changes and associated threats. Genomics will undoubtedly play a major role over the next decade and beyond, not only to further understand the mechanisms underlying adaptation and evolution but also to develop and implement innovative management and policy actions to preserve the adaptability of natural forests and intensively managed plantations

Stress neuropeptide levels in adults with chest pain due to coronary artery disease: potential implications for clinical assessment

: Substance P (SP) and neuropeptide Y (NPY) are neuropeptides involved in nociception. The study of biochemical markers of pain in communicating critically ill coronary patients may provide insight for pain assessment and management in critical care. Purpose of the study was to to explore potential associations between plasma neuropeptide levels and reported pain intensity in coronary critical care adults, in order to test the reliability of SP measurements for objective pain assessment in critical care