Marcadores predictivos en el trasplante y la carcinogénesis pulmonar.Análisis metabolómico y ruta de señalización DYRK2-SIAH2

El cáncer de pulmón continúa representado la primera causa de muerte por cáncer en el mundo. Esta alta mortalidad refleja, en parte, la limitada eficacia de la terapias actualmente disponibles. Globalmente, el cáncer de pulmón supera en mortalidad a los siguientes tres cánceres más prevalentes juntos (colon, mama y próstata), siendo además el principal contribuyente de nuevos casos de cáncer diagnosticado. La supervivencia global a los 5 años en el cáncer de pulmón ha experimentado pocos cambios en las últimas 3 décadas, permaneciendo en cifras tan bajas como del 11- 15%. Dada la pobre supervivencia actual del cáncer de pulmón, y la evidencia existente de que el diagnóstico precoz de la enfermedad reduce la mortalidad, en los últimos años ha cobrado especial interés la búsqueda de biomarcadores del cáncer de pulmón. HIPK2 y DYRK2, miembros de la familia de quinasas DYRK (dual-specificity tyrosine-regulated kinases), fosforilan SIAH2, modificando así su actividad. En los últimos años se ha atribuido a DYRK2 un posible papel relevante en el desarrollo y/o progresión tumoral asociado con la inducción de la apoptosis en respuesta a estrés oncogénico. En este sentido, DYRK2 fue identificado como el gen más frecuentemente sobre-expresado en el adenocarcinoma pulmón, así como un marcador de pronóstico favorable en este tipo de tumores. Recientemente se ha identificado una regulación mutua entre DYRK2 y la ubiquitin-ligasa SIAH2, en el control de la respuesta a hipoxia y rutas de señalización en el daño genotóxico. El reciente descubrimiento de la existencia de la delección de HIPK2 (con la consiguiente inactivación de p53) en fibroblastos de pulmón, sugiere la existencia de una alteración en la ruta proapoptótica independiente de caspasas. Esta quinasa forma parte de un grupo de enzimas altamente conservadas evolutivamente, pertenecientes a la familia de quinasas DYRK, las cuales juegan un papel clave en la regulación de procesos celulares y de desarrollo, tales como la proliferación y diferenciación celular, la neurogénesis y la citocinesis. El papel de la familia de quinasas DYRK en el cáncer de pulmón es poco conocido, aunque se sabe que desempeña un papel clave en la respuesta al daño al ADN. Así, DYRK2 fosforila a p53 en respuesta al daño genotóxico, induciendo así la apoptosis celular. La búsqueda de nuevas dianas y estrategias terapéuticas es un paso clave para la lucha contra el cáncer de pulmón. En los últimos años se ha producido un desarrollo exponencial de las ciencias ‘omicas’, destacando especialmente la metabolómica. La metabolómica puede definirse como un análisis contextualizado,...Lung cancer continues to be the leading cause of cancer-related mortality worldwide. The high mortality highlights the limited efficacy of available therapies for lung cancer treatment. Globally, lung cancer mortality rates exceed those of the next 3 more prevalent cancers combined, the and is largest contributor to new cancer diagnoses. Overall 5-year survival for lung cancer has shown little improvement over the last three decades, remaining as low as 11-15%. Given the poor survival rate of lung cancer, and considering that early diagnosis reduces mortality, special interest in searching for lung cancer biomarkers have been made recently. HIPK2 and DYRK2, members of the DYRK family (dual-specificity tyrosineregulated kinases), phosphorylate SIAH2, therefore modifying its activity. Recently, it has been suggested a possible role of DYRK2 in the development and/or progression of tumors, related to the induction of apoptosis in response oncogenic stress. In this regard, DYRK2 was identified as the most commonly up-regulated gene in lung adenocarcinomas, as well as a favourable prognostic factor in this type of tumors. In the recent years, a mutual regulation between DYRK2 and the ubiquitin-ligase SIAH2 in response to hypoxia and DNA-damage signaling pathways has been demonstrated. The finding of the deletion of HIPK2 (and, subsequently, the inactivation of p53) in lung fibroblasts suggest an alteration of the caspase-dependent proapoptotic route. This kinase belongs to an evolutionarily conserved enzyme family, which belongs to the DYRK family, playing an important role in the regulation of cellular processes and development, such as cell proliferation and differentiation, neurogenesis and cytogenesis. The role of the DYRK family in lung cancer is not well-known, although evidence exists that it phosphorylates p53 in response to genotoxic damage, therefore inducing cell apoptosis. It is of paramount importance to search for new targets and therapeutic strategies in lung cancer. In the last years, ‘omics’ sciences and, above all, metabolomics, have developed exponentially. Metabolimics can be defined as a quantitative and qualitative analysis of endogenous low-molecular weight metabolites of a biological system. Lung transplantation is the only available and effective treatment modality for end-stage respiratory diseases. Only 20% of all multiorgan donors provide lungs suitable for transplantation, because lung is specially vulnerable to be damaged during brain death. In order to increase lung donor pool, several lung transplant groups have relaxed classic acceptance criteria, accepting marginal donor lungs, as results of lung..

Teaching materials in electronic format for medical education in the subject of Surgical Proceedings in the degree of Medicine

La Cirugía es la parte de la Medicina que tiene por objeto curar las enfermedades por medio de operaciones hechas con las manos o a través de instrumentos. Hasta ahora, la enseñanza de la asignatura de “Procedimientos Quirúrgicos”, que corresponde a los estudiantes de segundo curso del Grado en Medicina de la Universidad de Córdoba, se ha llevado a cabo según el estilo tradicional. Se ha llevado a cabo un proyecto específico de elaboración de una herramienta multimedia, en concreto, un ebook, con el contenido teórico y práctico de la asignatura de Procedimientos Quirúrgicos, para mejorar la docencia médica según las directrices del Espacio Europeo de Educación Superior (EEES), fomentando así el desarrollo de una educación médica de calidad.Surgery is the branch of Medicine concerned with diseases and conditions requiring or amenable to operative or manual procedures. To date, teaching the subject of Surgical Procedures for 2nd-year students of the degree of Medicine has been done in a traditional manner. We have developed a specific project, with the creation of a multimedia resource consisting in an ebook with the theoretical and practical content of the Surgical Proceedings subject, in order to improve medical learning following the principles of the European Higher Education Area. This will aid in promoting the development of a high-quality medical teaching

Innovative and thorough practice to certify reference materials for sensory defects of olive oil

An important problem in the olive sector is the occasional mismatch of results obtained by different tasting panels when the same olive oil sample is analysed. These discrepancies could be minimised by using reference materials (RM) for taster training. A comprehensive protocol based on the combined use of sensory and instrumental analysis for the certification of olive oil batches as RMs, developed within the framework of the project ’Operational Group INTERPANEL’, is proposed. Similarity indices (R2, cosθ and NEAR) applied on GC–MS fingerprints, allow a successful homogeneity and stability assessment of produced batches. Furthermore, the use of robust statistics combined with a set of instructions developed to remove outliers were applied with excellent results on sensory data set provided by supra-panel composed by more than 100 qualified tasters. This work is the first to provide a comprehensive protocol for certification of real olive oil samples as RM for sensory analysis.European Agricultural Fund for Rural Development (EAFRD)Consejería de Agricultura, Ganadería, Pesca y Desarrollo SostenibleBiblioteca de la Universidad de Granad

Survival After Lung Transplantation for Chronic Hypersensitivity Pneumonitis: Results From a Large International Cohort Study

Repeated exposure to antigens via inhalation is the primary cause of hypersensitivity pneumonitis, a form of interstitial pneumonia. The chronic form of hypersensitivity pneumonitis leads to progressive loss of respiratory function; lung transplantation is the only therapeutic option for chronically ill patients. The ESTS Lung Transplantation Working Group conducted a retrospective multicentred cohort study to increase the body of knowledge available on this rare indication for lung transplantation. Data were collected for every patient who underwent lung transplant for hypersensitivity pneumonitis in participating centres between December 1996 and October 2019. Primary outcome was overall survival; secondary outcome was freedom from chronic lung allograft dysfunction. A total of 114 patients were enrolled from 9 centres. Almost 90% of patients were diagnosed with hypersensitivity pneumonitis before transplantation, yet the antigen responsible for the infection was identified in only 25% of cases. Eighty per cent of the recipients received induction therapy. Survival at 1, 3, and 5 years was 85%, 75%, and 70%, respectively. 85% of the patients who survived 90 days after transplantation were free from chronic lung allograft dysfunction after 3 years. The given study presents a large cohort of HP patients who underwent lung transplants. Overall survival rate is higher in transplanted hypersensitivity pneumonitis patients than in those suffering from any other interstitial lung diseases. Hypersensitivity pneumonitis patients are good candidates for lung transplantation

Generating new fanca-deficient hnscc cell lines by genomic editing recapitulates the cellular phenotypes of fanconi anemia

Fanconi anemia (FA) patients have an exacerbated risk of head and neck squamous cell carcinoma (HNSCC). Treatment is challenging as FA patients display enhanced toxicity to standard treatments, including radio/chemotherapy. Therefore, better therapies as well as new disease models are urgently needed. We have used CRISPR/Cas9 editing tools in order to interrupt the human FANCA gene by the generation of insertions/deletions (indels) in exon 4 in two cancer cell lines from sporadic HNSCC having no mutation in FA-genes: CAL27 and CAL33 cells. Our approach allowed efficient editing, subsequent purification of single-cell clones, and Sanger sequencing validation at the edited locus. Clones having frameshift indels in homozygosis did not express FANCA protein and were selected for further analysis. When compared with parental CAL27 and CAL33, FANCA-mutant cell clones displayed a FA-phenotype as they (i) are highly sensitive to DNA interstrand crosslink (ICL) agents such as mitomycin C (MMC) or cisplatin(ii) do not monoubiquitinate FANCD2 upon MMC treatment and therefore (iii) do not form FANCD2 nuclear foci, and (iv) they display increased chromosome fragility and G2 arrest after diepoxybutane (DEB) treatment. These FANCA-mutant clones display similar growth rates as their parental cells. Interestingly, mutant cells acquire phenotypes associated with more aggressive disease, such as increased migration in wound healing assays. Therefore, CAL27 and CAL33 cells with FANCA mutations are phenocopies of FA-HNSCC cells

COVID-19 outbreaks in a transmission control scenario: challenges posed by social and leisure activities, and for workers in vulnerable conditions, Spain, early summer 2020

Severe acute respiratory syndrome coronavirus 2 community-wide transmission declined in Spain by early May 2020, being replaced by outbreaks and sporadic cases. From mid-June to 2 August, excluding single household outbreaks, 673 outbreaks were notified nationally, 551 active (>6,200 cases) at the time. More than half of these outbreaks and cases coincided with: (i) social (family/friends’ gatherings or leisure venues) and (ii) occupational (mainly involving workers in vulnerable conditions) settings. Control measures were accordingly applied

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

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery