Caspases in virus-infected cells contribute to recognition by CD8+ T lymphocytes

CD8(+) cytotoxic T lymphocytes recognize infected cells in which MHC class I molecules present pathogen-derived peptides that have been processed mainly by proteasomes. Many infections induce a set of proteases, the caspases involved in apoptosis or inflammation. In this study, we report that processing and presentation of a short vaccinia virus-encoded Ag can take place also by a nonproteasomal pathway, which was blocked in infected cells with chemical inhibitors of caspases. By cleaving at noncanonical sites, at least two caspases generated antigenic peptides recognized by T lymphocytes. The sites and the peptidic products were partially overlapping but different to those used and produced by proteasomes in vitro. Antigenic natural peptides produced in infected cells by either pathway were quantitatively and qualitatively similar. Finally, coexpression of the natural vaccinia virus protein B13, which is an inhibitor of caspases and apoptosis, impaired Ag presentation by the caspase pathway in infected cells. These data support the hypothesis that numerous cellular proteolytic systems, including those induced during infection, such as caspases involved in apoptosis or in inflammation, contribute to the repertoire of presented peptides, thereby facilitating immunosurveillance.This work was supported by grants provided by the European Union, Ministerio de Ciencia e Innovación, Comunidad de Madrid, and Instituto de Salud Carlos III (to M.D.V.) and Programa Ramón y Cajal, Comunidad de Madrid, and Instituto de Salud Carlos III (to D.L.). G.L.S. is a Wellcome Principal Research Fellow.S

Propiedades de nanocompuestos de matriz termoestable con nuevos organosilicatos laminares

En este trabajo se han preparado nanocompuestos de matriz polímero termoestable del tipo poliéster insaturado y epoxídica utilizando como refuerzo nanosilicatos laminares que se han modificado específicamente para mejorar la interacción con la matriz. En concreto se han modificado montmorillonitas con cationes orgánicos reactivos con la matriz de poliéster insaturado. Asimismo se han silanizado montmorillonitas comerciales orgánicamente modificadas con el objetivo de formar enlaces químicos con la matriz epoxídica. En ambos nanocompuestos se han estudiado las propiedades termo- mecánicas pudiendo comprobar la efectividad de los nuevos organosilicatos

Recent reforms in Spanish housing markets: an evaluation using a DSGE model

After a long academic debate, Spain finally repealed in 2012 the deduction for home purchase. The abrogation took effect in 2013. In parallel, the VAT for the purchase of new housing was increased after a short period in which it had a reduced rate. The aim of this paper is to assess the macroeconomic effects of these two relevant housing market reforms. In order to do that, we use a dynamic stochastic general equilibrium (DSGE) model calibrated to capture the key ratios of the Spanish economy. The model includes a housing market, covering both the rental market side and the property market side and credit-constrained agents. We find that these measures drive down housing prices and have a negative impact on output and employment in the construction sector. However, in the long run, this last effect is offset by the benefits of a reduction in distortionary taxes

Evaluation and comparison of the performance of five prediction models of in-hospital mortality in patients with acute heart failure

Objetivo: Los modelos de predicción de mortalidad intrahospitalaria en pacientes con falla cardiaca aguda pueden ser útiles para la toma de decisiones, situación que hace necesario evaluar la capacidad predictiva y de discriminación en la población colombiana. Método: Estudio de cohorte retrospectiva de pacientes con falla cardiaca aguda. Se evaluó el desempeño de los modelos de predicción de mortalidad intrahospitalaria ADHERE, OPTIMIZE-HF, GWTG-HF y PROTECT, durante los años 2013 a 2015. Se realizó el cálculo de la puntuación para cada uno de los modelos y se determinó la capacidad de predicción y discriminación. Resultados: Se incluyeron 776 pacientes con una edad promedio de 71.5 años (desviación estándar: 14.3), el 56% hombres, con fracción de eyección del ventrículo izquierdo del 39%. La mortalidad global fue del 6.1%. El área bajo la curva para ADHERE fue de 0.56 (intervalo de confianza del 95% [IC95%]: 0.49-0.64), para EHMRG de 0.63 (IC95%: 0.55-0.71], para GWTG-HF de 0.63 (IC95%: 0.55-0.70), para OPTIMIZE de 0.65 (IC95%: 0.56-0.74) y para PROTECT de 0.69 (IC95%: 0.60-0.77). Conclusiones: Los modelos de predicción de muerte intrahospitalaria en pacientes con falla cardiaca aguda muestran pobre desempeño y baja capacidad de predicción y discriminación en población colombiana, lo cual sugiere el desarrollo de escalas de predicción de mortalidad en pacientes con falla cardiaca aguda específicas para dicha población.Q4Objective: In-hospital mortality prediction models on acute heart failure can be beneficial for decision-making, a situation necessary to evaluate, our goal was to compare predictive and discriminatory capacity of Colombian population. Method: A retrospective cohort study in patients with acute heart failure was conducted. The following performance evaluation of in-hospital mortality prediction models were conducted from 2013 to 2015: ADHERE, EHMRG, OPTIMIZE-HF, GWTG-HF and PROTECT. Data was calculated for each model, prediction and discriminatory capacity was evaluated. Results: A sample of 776 patients, 56% male, with an average age of 71.5 (standard deviation: 14.3) and with left ventricle ejection fraction rate of 39% was studied. Global mortality was of 6.1%. The area under curve for ADHERE was of 0.56 (95% confidence interval [95% CI]: 0.49-0.64), for EHMRG 0.63 (95% CI: 0.55-0.71), for GWTG-HF 0.63 (95% CI: 0.55-0.70), for OPTIMIZE 0.65 (95% CI: 0.56-0.74) and for PROTECT 0.69 (95% CI: 0.60-0.77). Conclusions: The models for predicting in-hospital death in patients with acute heart failure show poor performance, predictability and discrimination in the Colombian population, suggesting the development of mortality prediction scales in patients with acute heart failure specific to our population.Revista Nacional - Indexad

Alojamientos protegidos para enfermos mentales crónicos 1: Perfil epidemiológico, síntomas, calidad de vida y autoestima en dos muestras de sujetos

En este estudio se comparan los síntomas psicopatológicos, la calidad de vida y la autoestima de dos muestras de pacientes mentales crónicos, unos que residen en 2 alojamientos protegidos y otros en espera de hacerlo. También se precisa el perfil epidemiológico de los pacientes. Este tipo de alojamientos se presentan desde hace algunas décadas como la alternativa a los hospitales psiquiátricos tradicionales, que funcionaban en la práctica como recursos residenciales. Su utilidad ha sido considerada desde diferentes puntos de vista, a nivel clínico, asistencial, funcional y económico. A diferencia de otros hallazgos, en nuestro estudio no se aprecia una mejor calidad de vida de los pacientes que viven en dichos alojamientos frente a los que no lo hacen. Tampoco están mejor psicopatológicamente ni tienen mayor autoestima. Se sugieren modificaciones metodológicas en el diseño que permitan controlar ciertas variables que pueden influir en los resultados.In this study the psychopathology symptoms, the quality of life and the selfesteem of two samples of patient mental chronic are compared, some housed in protected lodgings and others while waiting for making it. It is also described the epidemic profile of the patients. This type of lodgings is presented for some decades like the alternative to the traditional psychiatric hospitals that worked in the practice as residential resources. Their utility has been considered from different points of view, at clinical, assistance, functional and economic level. Contrary to other discoveries, in our study a better quality of the patients' life is not appreciated that live in this lodgings in front of those that don't make it. Neither they are better psychopathologically neither they have bigger self-esteem. Methodological modifications are suggested in the design to control certain variables that can influence in the results

Concordance between circulating tumor cells and clinical status during follow-up in anaplastic lymphoma kinase (ALK) non-small-cell lung cancer patients

Background: The identification of anaplastic lymphoma kinase (ALK) rearrangements is found in approximately 5% of non-small-cell lung cancers (NSCLCs). However, the development of liquid biopsies as a diagnostic tool is less developed in these cases. This study investigates the use of CTCs during treatment, together with an extended follow-up to correlate with clinical evolution. Patients and Methods: A total of 13 patients out of a cohort of 212 patients with lung adenocarcinoma, presented ALK rearrangements (6%) confirmed by tumor biopsy. A total of 60 serial blood samples were collected from these patients who were prospectively enrolled in the study. Results: All patients had a positive CTC count at baseline (mean = 3). The median follow-up was 9 months (range 1-17 months). Three patients underwent surgery and their CTC counts decreased after the procedure but still remained detectable. After radiotherapy, 3 cases showed an average decrease of 5 CTCs. A total of 6 patients were treated with ALK inhibitors and a partial response was observed in 3 of them, who also presented decreased CTC counts. The other 3 patients presented primary resistance, and their CTC counts were higher than those obtained prior to progression. Conclusion: We believe that the use of CTCs for dynamic monitoring of NSCLC with ALK rearrangement and to detect disease persistence or recurrence may be a reliable technique. CTC counts may also have potential use to monitor the efficacy of ALK inhibitors, facilitating detection of resistance to treatmentThis study was supported by Carlos III Institute of Health, Spanish Ministry of Science and Innovation, and European Regional Development Fund (grant number: PI16/01818 and PIE14/00064), D. Pérez-Callejo is supported by SEOM-Río-Hortega contract, A Romero is supported by Joan Rodés fellowship (grant number: JR14/00017) and M Sánchez-Beato is supported by Miguel Servet contract (CP11/00018 and CPII16/00024

Improvement of the teaching and learning process in the department of business administration and economic history

El Espacio Europeo de Educación Superior (EEES) se centra en el proceso de enseñanza/aprendizaje de competencias. Para que dicho proceso pueda llevarse a cabo adecuadamente es necesario que los estudiantes desarrollen estrategias de estudio y aprendizaje y los profesores nuevos métodos de enseñanza. Precisamente la innovación educativa consiste en llevar a cabo cambios que mejoren dicho proceso de enseñanza y aprendizaje. El objetivo de este trabajo es descubrir las percepciones que los estudiantes tienen acerca de dichas estrategias y métodos, para obtener información a partir de la cual llevar a cabo mejoras e innovaciones en el proceso educativo. Se trata de estudiantes de grados a los que el Departamento de dirección de empresas e historia económica imparte docencia. Los resultados permiten concluir que los estudiantes tienen percepciones claras acerca de las estrategias de estudio/aprendizaje y de los métodos de enseñanza que podrían utilizar los profesores para mejorar el logro académico. También se concluye que existen diferencias por género y ciclo académico, y que es posible generar dos modelos causales explicativos de la percepción de logro del estudiante, uno relativo a las estrategias de estudio y aprendizaje, otro respecto a los métodos de enseñanza del profesoradoThe European Higher Education Space (EHES) focuses on the teaching/learning competencies process. So that this process can be carried out properly it is necessary for students to develop study and learning strategies and new teachers teaching methods. Precisely educational innovation is to carry out changes that improve the teaching and learning process. The aim of this work is to discover student´s perceptions about these strategies and methods, to obtain information from which to carry out improvements and innovations in the educational process. They are students from grades in which teachers of the Department of Business Administration and Economic History work. The results allow show that students have clear perceptions of study/learning and strategies of teaching methods that the teachers could use to improve academic achievement. Also it is concluded that differences exist by gender and academic cycle, and that it is possible to generate two explanatory causal models of perception on achievement of student, one relating to learning and study strategies, another on faculty teaching methods

Association between use of enhanced recovery after surgery protocol and postoperative complications in colorectal surgery: the postoperative outcomes within enhanced recovery after surgery protocol (power) study

Importance: enhanced Recovery After Surgery (ERAS) care has been reported to be associated with improvements in outcomes after colorectal surgery compared with traditional care. Objective: to determine the association between ERAS protocols and outcomes in patients undergoing elective colorectal surgery. Design, setting, and participants: the Postoperative Outcomes Within Enhanced Recovery After Surgery Protocol (POWER) Study is a multicenter, prospective cohort study of 2084 consecutive adults scheduled for elective colorectal surgery who received or did not receive care in a self-declared ERAS center. Patients were recruited from 80 Spanish centers between September 15 and December 15, 2017. All patients included in this analysis had 1 month of follow-up. Exposures: colorectal surgery and perioperative management were the exposures. Twenty-two individual ERAS items were assessed in all patients, regardless of whether they were included in an established ERAS protocol. Main outcomes and measures: the primary study outcome was moderate to severe postoperative complications within 30 days after surgery. Secondary outcomes included ERAS adherence, mortality, readmissions, reoperation rates, and hospital length of stay. Results: between September 15 and December 15, 2017, 2084 patients were included in the study. Of these, 1286 individuals (61.7%) were men; mean age was 68 years (interquartile range [IQR], 59-77). A total of 879 patients (42.2%) presented with postoperative complications and 566 patients (27.2%) developed moderate to severe complications. The number of patients with moderate or severe complications was lower in the ERAS group (25.2% vs 30.3%; odds ratio [OR], 0.77; 95% CI, 0.63-0.94; P¿=¿.01). The overall rate of adherence to the ERAS protocol was 63.6% (IQR, 54.5%-77.3%), and the rate for patients from hospitals self-declared as ERAS was 72.7% (IQR, 59.1%-81.8%) vs non-ERAS institutions, which was 59.1% (IQR, 50.0%-63.6%; P¿<¿.001). Adherence quartiles among patients receiving the highest and lowest ERAS components showed that the patients with the highest adherence rates had fewer moderate to severe complications (OR, 0.34; 95% CI, 0.25-0.46; P¿<¿.001), overall complications (OR, 0.33; 95% CI, 0.26-0.43; P¿<¿.001), and mortality (OR, 0.27; 95% CI, 0.07-0.97; P¿=¿.06) compared with those who had the lowest adherence rates. Conclusions and relevance: an increase in ERAS adherence appears to be associated with a decrease in postoperative complications

Pobreza en la ocupación e instrumentos de reacción

Unión Europea,Ministerio de Economía y Competitividad y el Fondo Europeo de Desarrollo Regional DER2015-63701-C3-1-

Osimertinib in advanced EGFR-T790M mutation-positive non-small cell lung cancer patients treated within the Special Use Medication Program in Spain : OSIREX-Spanish Lung Cancer Group

AURA study reported 61% objective response rate and progression-free survival of 9.6 months with osimertinib in patients with EGFR/T790M+ non-small cell lung cancer. Due to lack of real-world data, we proposed this study to describe the experience with osimertinib in Spain. Post-authorization, non-interventional Special Use Medication Program, multicenter, retrospective study in advanced EGFR/T790M+ non-small cell lung cancer. One hundred-fifty five patients were enrolled (August 2016-December 2018) from 30 sites. Primary objective: progression-free survival. Secondary objectives: toxicity profile, objective response rate, and use of health service resources. 70% women, median age 66. 63.9% were non-smokers and 99% had adenocarcinoma. Most patients had received at least one prior treatment (97%), 91.7% had received previous EGFR-tyrosine kinase inhibitors and 2.8% osimertinib as first-line treatment. At data cutoff, median follow-up was 11.8 months. One hundred-fifty five patients were evaluable for response, 1.3% complete response, 40.6% partial response, 31% stable disease and 11.6% disease progression. Objective response rate was 42%. Median progression-free survival was 9.4 months. Of the 155 patients who received treatment, 76 (49%) did not reported any adverse event, 51% presented some adverse event, most of which were grade 1 or 2. The resource cost study indicates early use is warranted. This study to assess the real-world clinical impact of osimertinib showed high drug activity in pretreated advanced EGFR/T790M+ non-small cell lung cancer, with manageable adverse events. Clinical trial registration number : NCT03790397