Redox-dependent and redox-independent functions of Caenorhabditis elegans thioredoxin 1

Thioredoxins (TRX) are traditionally considered as enzymes catalyzing redox reactions. However, redox-independent functions of thioredoxins have been described in different organisms, although the underlying molecular mechanisms are yet unknown. We report here the characterization of the first generated endogenous redox-inactive thioredoxin in an animal model, the TRX-1 in the nematode Caenorhabditis elegans. We find that TRX-1 dually regulates the formation of an endurance larval stage (dauer) by interacting with the insulin pathway in a redox-independent manner and the cGMP pathway in a redox-dependent manner. Moreover, the requirement of TRX-1 for the extended longevity of worms with compromised insulin signalling or under calorie restriction relies on TRX-1 redox activity. In contrast, the nuclear translocation of the SKN-1 transcription factor and increased LIPS-6 protein levels in the intestine upon trx-1 deficiency are strictly redox-independent. Finally, we identify a novel function of C. elegans TRX-1 in male food-leaving behaviour that is redox-dependent. Taken together, our results position C. elegans as an ideal model to gain mechanistic insight into the redox-independent functions of metazoan thioredoxins, overcoming the limitations imposed by the embryonic lethal phenotypes of thioredoxin mutants in higher organisms.NIH Office of Research Infrastructure P40 OD010440Spanish Ministry of Economy and Competitiveness BFU2015- 64408-PFondo Social Europeo BFU2015- 64408-PNational Institute of Allergy and Infectious Diseases of the National Institutes of Health R01AI07640

Key market values for bottled wine in an emerging market: product attributes or business strategy?

This article focuses on the emerging bottled Chilean red wine market and studies the main determinants of the consumer price of wine sold on the domestic market. A hedonic price function was estimated for a sample of 810 wines using a quantile regression (QR) model. The database contains three variables groups to explain price: objective variables (national, international, and vine quality designations), subjective variables (wine score), and business strategies used by wine producers.Postprint (author's final draft

La enseñanza en el máster de abogacía a través del análisis de casos reales de carácter multidisciplinar. Aprendizaje "a partir del estudio de razonamientos parciales temáticos"

Generar blog para publicaciones de alumnos del Máster Abogacía, con "entradas" dirigidas. Habría análisis desde varias disciplinas añadiéndose estudios con enfoque basado en otras áreas de conocimiento, generando interdisciplinariedad

Rosalía de Castro Álvaro Paradela Grabado á Pluma

Investigación realizada desde el grupo de investigación en torno al grabado a la pluma, con tinta dulce sobre metal

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Effectiveness of a strategy that uses educational games to implement clinical practice guidelines among Spanish residents of family and community medicine (e-EDUCAGUIA project):A clinical trial by clusters

This study was funded by the Fondo de Investigaciones Sanitarias FIS Grant Number PI11/0477 ISCIII.-REDISSEC Proyecto RD12/0001/0012 AND FEDER Funding.Background: Clinical practice guidelines (CPGs) have been developed with the aim of helping health professionals, patients, and caregivers make decisions about their health care, using the best available evidence. In many cases, incorporation of these recommendations into clinical practice also implies a need for changes in routine clinical practice. Using educational games as a strategy for implementing recommendations among health professionals has been demonstrated to be effective in some studies; however, evidence is still scarce. The primary objective of this study is to assess the effectiveness of a teaching strategy for the implementation of CPGs using educational games (e-learning EDUCAGUIA) to improve knowledge and skills related to clinical decision-making by residents in family medicine. The primary objective will be evaluated at 1 and 6months after the intervention. The secondary objectives are to identify barriers and facilitators for the use of guidelines by residents of family medicine and to describe the educational strategies used by Spanish teaching units of family and community medicine to encourage implementation of CPGs. Methods/design: We propose a multicenter clinical trial with randomized allocation by clusters of family and community medicine teaching units in Spain. The sample size will be 394 residents (197 in each group), with the teaching units as the randomization unit and the residents comprising the analysis unit. For the intervention, both groups will receive an initial 1-h session on clinical practice guideline use and the usual dissemination strategy by e-mail. The intervention group (e-learning EDUCAGUIA) strategy will consist of educational games with hypothetical clinical scenarios in a virtual environment. The primary outcome will be the score obtained by the residents on evaluation questionnaires for each clinical practice guideline. Other included variables will be the sociodemographic and training variables of the residents and the teaching unit characteristics. The statistical analysis will consist of a descriptive analysis of variables and a baseline comparison of both groups. For the primary outcome analysis, an average score comparison of hypothetical scenario questionnaires between the EDUCAGUIA intervention group and the control group will be performed at 1 and 6months post-intervention, using 95% confidence intervals. A linear multilevel regression will be used to adjust the model. Discussion: The identification of effective teaching strategies will facilitate the incorporation of available knowledge into clinical practice that could eventually improve patient outcomes. The inclusion of information technologies as teaching tools permits greater learning autonomy and allows deeper instructor participation in the monitoring and supervision of residents. The long-term impact of this strategy is unknown; however, because it is aimed at professionals undergoing training and it addresses prevalent health problems, a small effect can be of great relevance. Trial registration: ClinicalTrials.gov: NCT02210442.Publisher PDFPeer reviewe

All-cause mortality in the cohorts of the Spanish AIDS Research Network (RIS) compared with the general population: 1997Ł2010

Abstract Background: Combination antiretroviral therapy (cART) has produced significant changes in mortality of HIVinfected persons. Our objective was to estimate mortality rates, standardized mortality ratios and excess mortality rates of cohorts of the AIDS Research Network (RIS) (CoRIS-MD and CoRIS) compared to the general population. Methods: We analysed data of CoRIS-MD and CoRIS cohorts from 1997 to 2010. We calculated: (i) all-cause mortality rates, (ii) standardized mortality ratio (SMR) and (iii) excess mortality rates for both cohort for 100 personyears (py) of follow-up, comparing all-cause mortality with that of the general population of similar age and gender. Results: Between 1997 and 2010, 8,214 HIV positive subjects were included, 2,453 (29.9%) in CoRIS-MD and 5,761 (70.1%) in CoRIS and 294 deaths were registered. All-cause mortality rate was 1.02 (95% CI 0.91-1.15) per 100 py, SMR was 6.8 (95% CI 5.9-7.9) and excess mortality rate was 0.8 (95% CI 0.7-0.9) per 100 py. Mortality was higher in patients with AIDS, hepatitis C virus (HCV) co-infection, and those from CoRIS-MD cohort (1997. Conclusion: Mortality among HIV-positive persons remains higher than that of the general population of similar age and sex, with significant differences depending on the history of AIDS or HCV coinfection

Regulation of longevity by liv-7(pv17)

Resumen del trabajo presentado al 4th Spanish Worm Meeting, celebrado en Carmona (Sevilla) del 14 al 15 de marzo de 2013.The main objectives of this project have been the identification and characterization of a novel gene that regulates longevity in Caenorhabditis elegans. Previously, our group isolated a new long-lived mutant named liv-7 (pv17) that does not show any other visible phenotype beside the longevity phenotype. Genetic mapping of the mutation showed that liv-7 is located near to the center of chromosome V where no other long-lived mutant has been located before. Genetic interactions of liv-7 (pv17) suggest that liv-7 is involved in the control of longevity induced by germline depletion since its longevity require the transcription factors daf-16, daf-12 and pha-4, as well as kri-1, nhr-80 and tcer-1 which have been shown essential and specific for the longevity of germline depletion animals. Furthermore, liv-7 increases the intestinal nuclear localization of daf-16 a feature observed in animals without germline. In addition, the longevity of liv-7 mutant in a germline absence mutant background is not additive of the longevity observed in any of the singles. However, liv-7 mutant shows an additive increase of lifespan in different mutant backgrounds as reducing the function of the insulin/IGF pathway, sensory perception or under caloric restriction. Interestingly, the transcriptional expression of liv-7 is primarily located in four pairs of sensory neurons, ADF and ASE in the head, and PHA and PHB in the tail. All these results suggest that liv-7 could be acting in an endocrine way to regulated longevity in C. elegans, joining environmental cues and reproductive status of the animal.Peer Reviewe

Identificación y caracterización del mutante longevo liv-7 (pv17) en Caenorhabditis elegans

Resumen del póster presentado al XXXVII Congreso de la Sociedad Española de Genética, celebrado en Torremolinos (Málaga) del 29 de septiembre al 2 de octubre de 2009.La búsqueda de mutantes termosensibles en el nematodo Caenorhabditis elegans nos ha permitido identificar mutantes que también son longevos, como es el caso de liv-7(pv17). Este mutante además de las características citadas no presenta ningún fenotipo visible, lo cual hace muy complicado la identificación del gen mediante mapeo genético. En un intento de superar dicho problema, creamos dobles mutantes con mutantes longevos ya descritos con la esperanza de que alguno de esos dobles generara un fenotipo sinérgico visible. Este fenotipo lo hemos encontrado en un doble daf-2(e1370); liv-7(pv17), el cual presenta una parada de desarrollo en el primer estadio larvario (L1), un fenotipo no observado en ninguno de los simples. El gen daf-2 codifica al único receptor homólogo al de la insulina/IGF en C. elegans, y es conocido como un elemento clave en la regulación de la longevidad desde invertebrados hasta mamíferos. Utilizando el doble mutante daf-2(e1370); liv-7(pv17) hemos conseguido acotar la mutación liv-7(pv17), mediante mapeo con snip-SNP, en la región central del cromosoma V. Realizando transgénicos con genes situados en esa región hemos conseguido rescatar el fenotipo que genera daf-2(e1370); liv-7(pv17) con un fragmento que lleva un gen que codifica para una arilsulfatasa. Mediante secuenciación de la cepa mutante y la cepa silvestre hemos confirmado que este gen es el que está mutado en liv-7(pv17).Peer reviewe