Cortistatin, a new antiinflammatory peptide with therapeutic effect on lethal endotoxemia

Cortistatin is a recently discovered cyclic neuropeptide related to somatostatin that has emerged as a potential endogenous antiinflammatory factor based on its production by and binding to immune cells. Because human septic shock involves excessive inflammatory cytokine production, we investigated the effect of cortistatin on the production of inflammatory mediators and its therapeutic action in various murine models of endotoxemia. Cortistatin down-regulated the production of inflammatory mediators by endotoxin-activated macrophages. The administration of cortistatin protected against lethality after cecal ligation and puncture, or injection of bacterial endotoxin or Escherichia coli, and prevented the septic shock-associated histopathology, such as infiltration of inflammatory cells and intravascular disseminated coagulation in various target organs. The therapeutic effect of cortistatin was mediated by decreasing the local and systemic levels of a wide spectrum of inflammatory mediators, including cytokines, chemokines, and acute phase proteins. The combined use of cortistatin and other antiinflammatory peptides was very efficient treating murine septic shock. This work provides the first evidence of cortistatin as a new immunomodulatory factor with the capacity to deactivate the inflammatory response. Cortistatin represents a potential multistep therapeutic agent for human septic shock, to be used in combination with other immunomodulatory agents or as a complement to other therapies

Productos extraordinarios en la construcción. Una revisión crítica

En los últimos años se han desarrollado infinidad de materiales en el ámbito de la construcción. A muchos de ellos se le atribuyen características y propiedades asombrosas, que muchas veces no existen, otras son cuentos comerciales o incluso a veces se magnifica su influencia en varios órdenes de magnitud. Ninguna de ellas está demostrada, ni respaldada por ningún estudio. En otros casos, el producto sí tiene esas facultades, pero es inaplicable a la vida real por alguna razón práctica (mantenimiento, durabilidad, incompatibilidad, etc.).Con este TFG se ha pretendido realizar un análisis crítico sobre el musgo y el hormigón autorreparable con bacterias y arrojar un poco de visibilidad sobre las propiedades reales que tienen. Ventajas e inconvenientes. Revisión a subvenciones para el desarrollo de estos materiales. <br /

Effectiveness of an Intervention Programme on Adherence to the Mediterranean Diet in a Preschool Child: A Randomised Controlled Trial.

Background: The Mediterranean diet is considered one of the dietary patterns with the most accumulated scientific evidence on health benefits. In children, it has positive effects in the prevention of obesity and cardiovascular diseases, as well as in the prevention of diabetes. We aimed to evaluate the medium-term efficacy of an intervention programme, targeting adherence to the Mediterranean diet among preschool children. Methods: In a randomised, parallel trial of participants aged 3–5 years, a school garden was attended in the experimental group, and in the control group, the usual content on the human body and health were taught. Adherence to the Mediterranean diet was assessed using the KIDMED questionnaire, controlling for weight, height, body mass index (BMI) and socio-demographic variables. Results: A reduction in BMI was found in the experimental group after one year and at the end of the follow-up period. In the overall score obtained in the KIDMED survey, a statistical trend was found between the two groups (p = 0.076). In multivariate analysis, consumption of pulses more than once a week’ was predictive of improved diet quality, with an Odds Ratio (OR) in the experimental group of 1.382 (95% CI 1.126–1.695; p = 0.009). Conclusions: The experimental approach improved the quality of the participants’ diet, increasing adherence to the Mediterranean diet due to increased consumption of plant-based protein.post-print461 K

Metodologías innovadoras en el ámbito universitario: coaching educativo en el seguimiento de Trabajos Fin de Master, Fin de Grado y Practicums

Se desarrolla una metodología coaching que incentiva y motiva el proceso de seguimiento de trabajo de fin de Master, fin de Grado y Prácticums para obtener resultados brillantes y a su vez mejore la competencia de los estudiantes en la evolución

Protective role of cortistatin in pulmonary inflammation and fibrosis

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, Grant/Award Number: 12/21767-5; Ministerio de Ciencia e Innovacion, Grant/Award Number: SAF2015-67787-RBackground and Purpose: Acute lung injury (ALI), acute respiratory distress syndrome (ARDS) and pulmonary fibrosis remain major causes of morbidity, mortality and a healthcare burden in critically ill patient. There is an urgent need to identify factors causing susceptibility and for the design of new therapeutic agents. Here, we evaluate the effectiveness of the immunomodulatory neuropeptide cortistatin to regulate pulmonary inflammation and fibrosis in vivo. Experimental Approach: ALI/ARDS and pulmonary fibrosis were induced experimentally in wild-type and cortistatin-deficient mice by pulmonary infusion of the bacterial endotoxin LPS or the chemotherapeutic drug bleomycin, and the histopathological signs, pulmonary leukocyte infiltration and cytokines, and fibrotic markers were evaluated. Key Results: Partially deficient mice in cortistatin showed exacerbated pulmonary damage, pulmonary inflammation, alveolar oedema and fibrosis, and subsequent increased respiratory failure and mortality when challenged to LPS or bleomycin, even at low doses. Treatment with cortistatin reversed these aggravated phenotypes and protected from progression to severe ARDS and fibrosis, after high exposure to both injury agents. Moreover, cortistatin-deficient pulmonary macrophages and fibroblasts showed exaggerated ex vivo inflammatory and fibrotic responses, and treatment with cortistatin impaired their activation. Finally, the protective effects of cortistatin in ALI and pulmonary fibrosis were partially inhibited by specific antagonists for somatostatin and ghrelin receptors. Conclusion and Implications: We identified cortistatin as an endogenous inhibitor of pulmonary inflammation and fibrosis. Deficiency in cortistatin could be a marker of poor prognosis in inflammatory/fibrotic pulmonary disorders. Cortistatin-based therapies could emerge as attractive candidates to treat severe ALI/ARDS, including SARS-CoV-2-associated ARDS.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) 12/21767-5Instituto de Salud Carlos III Spanish Government European Commission SAF2015-67787-

Preconditioning of Microglia by α-Synuclein Strongly Affects the Response Induced by Toll-like Receptor (TLR) Stimulation

In recent years, it has become accepted that α-synuclein (αSyn) has a key role in the microglia-mediated neuroinflammation, which accompanies the development of Parkinson's disease and other related disorders, such as Dementia with Lewy Bodies and Alzheimer's disease. Nevertheless, the cellular and molecular mechanisms underlying its pathological actions, especially in the sporadic forms of the diseases, are not completely understood. Intriguingly, several epidemiological and animal model studies have revealed a link between certain microbial infections and the onset or progression of sporadic forms of these neurodegenerative disorders. In this work, we have characterized the effect of toll-like receptor (TLR) stimulation on primary murine microglial cultures and analysed the impact of priming cells with extracellular wild-type (Wt) αSyn on the subsequent TLR stimulation of cells with a set of TLR ligands. By assaying key interleukins and chemokines we report that specific stimuli, in particular Pam3Csk4 (Pam3) and single-stranded RNA40 (ssRNA), can differentially affect the TLR2/1- and TLR7-mediated responses of microglia when pre-conditioned with αSyn by augmenting IL-6, MCP-1/CCL2 or IP-10/CXCL10 secretion levels. Furthermore, we report a skewing of αSyn-primed microglia stimulated with ssRNA (TLR7) or Pam3 (TLR2/1) towards intermediate but at the same time differential, M1/M2 phenotypes. Finally, we show that the levels and intracellular location of activated caspase-3 protein change significantly in αSyn-primed microglia after stimulation with these particular TLR agonists. Overall, we report a remarkable impact of non-aggregated αSyn pre-sensitization of microglia on TLR-mediated immunity, a phenomenon that could contribute to triggering the onset of sporadic α-synuclein-related neuropathologies

Analysis of the Interferon Gamma (rs2430561, +874T/A) Functional Gene Variant in Relation to the Presence of Cardiovascular Events in Rheumatoid Arthritis

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased cardiovascular (CV) morbidity and mortality. Since interferon-gamma (IFN-γ) has a direct effect on inflammation, in this study we assessed the potential association of the IFNG functional gene variant rs2430561 with CV disease in patients with RA. METHODS: One thousand six hundred and thirty-five patients fulfilling the 1987 American College of Rheumatology classification criteria for RA were genotyped for the IFNG (rs2430561, +874T/A) gene polymorphism using TaqMan genotyping assay. Patients were stratified according to the presence of CV events or not. Logistic regression models to explain the presence of CV disease according to the IFNG rs2430561 allele distribution were performed. The potential influence of this variant in the development of subclinical atherosclerosis was also analyzed in a subgroup of patients with no history of CV events to determine carotid artery intima-media thickness (IMT) (n = 286) and presence of carotid plaques. Levels of the cytokine were determined in a subgroup of patients by ELISA. RESULTS: Adjusted logistic regression model disclosed that presence of the minor allele A was not associated with increased risk of suffering CV events in RA patients. Besides, differences did not achieve statistical significance regarding carotid IMT and presence of carotid plaques in RA patients carrying IFNG rs2430561 variant allele. Levels of IFN-γ were higher in patients who had suffered CV events compared to patients who did not. CONCLUSION: Our results do not support a role of IFNG rs2430561 (+874T/A) functional gene variant in the development of CV disease in RA patients

Análisis de la traducción para el doblaje de la serie de animación Rick y Morty

Treball de Final de Grau en Traducció i Interpretació. Codi: TI0983. Curs acadèmic 2015-2016En este proyecto se analiza la calidad de la traducción para doblaje de una serie de animación, Rick y Morty, a partir del análisis de varios episodios. Para ello he seleccionado escenas de cuatro capítulos de la primera temporada de esta serie, y he analizado los casos en los que por falta de equivalencia, por diferencias culturales o por humor intraducible la traducción fuera compleja. También hago una crítica de la traducción (que no una evaluación) siguiendo el baremo de corrección de traducciones que se utiliza en la carrera de Traducción e Interpretación en la Universitat Jaume I y las indicaciones de Mona Baker, a modo de crítica aplicada.. Por un lado, el doblaje es un proceso increíblemente complejo, que tiene unas limitaciones impuestas por las imágenes a las que acompaña que la traducción de textos leídos no tiene, y donde además intervienen multitud de factores que restringen la libertad del traductor. Pero este trabajo reflexiona sobre el nivel de adecuación del doblaje a la serie, ya que se trata sin duda de una serie original y vanguardista que, en mi opinión, no tiene un doblaje igual de rompedor, y es el público español quien pierde. Por ello no analizo si el doblaje es bueno o malo, y en cambio prefiero analizar si el contenido que le llega al espectador español es, desde el punto de vista de los materiales teóricos, lo mejor posible. Al final de este proyecto explico las conclusiones objetivas a las que he llegado, basadas en el análisis lingüístico de los retos de traducción encontrados