Association study of lipoprotein(a) genetic markers, traditional risk factors, and coronary heart disease in HIV-1-infected patients.

Objectives: General population studies have shown associations between copy number variation (CNV) of the LPA gene Kringle-IV type-2 (KIV-2) coding region, single-nucleotide polymorphism (SNP) rs6415084 in LPA and coronary heart disease (CHD). Because risk factors for HIV-infected patients may differ from the general population, we aimed to assess whether these potential associations also occur in HIV-infected patients. Methods: A unicenter, retrospective, case-control (1:3) study. Eighteen HIV-patients with confirmed diagnosis of acute myocardial infarction (AMI) were adjusted for age, gender, and time since HIV diagnosis to 54 HIV-patients without CHD. After gDNA extraction from frozen blood, both CNV and SNP genotyping were performed using real-time quantitative PCR. All genetic and non-genetic variables for AMI were assessed in a logistic regression analysis. Results: Our results did not confirm any association in terms of lipoprotein(a) LPA structural genetic variants when comparing KIV-2 CNV (p = 0.67) and SNP genotypes (p = 0.44) between AMI cases and controls. However, traditional risk factors such as diabetes mellitus, hypertension, and CD4(+) T cell count showed association (p < 0.05) with CHD. Conclusion: Although significant associations of AMI with diabetes, hypertension and CD4(+) T cell count in HIV-patients were found, this study could not confirm the feasibility neither of KIV-2 CNV nor rs6415084 in LPA as genetic markers of CHD in HIV-infected patients.Highlights:● Individuals with HIV infection are at higher risk of coronary heart disease (CHD) than the non-infected population.● Our results showed no evidence of LPA structural genetic variants associated with CHD in HIV-1-infected patients.● Associations were found between diabetes mellitus, arterial hypertension, CD4(+) T cell count, and CHD.● The clinical usefulness of these biomarkers to predict CHD in HIV-1-infected population remains unproven.● Further studies are needed to assess the contribution of common genetic variations to CHD in HIV-infected individuals

ABPgame+ o cómo hacer del último curso de ingeniería una primera experiencia profesional

Algunos de los aspectos clave en el desarrollo profesional de un ingeniero son su capacidad para trabajar en equipo, para integrar diferentes puntos de vista y para desarrollar grandes proyectos con un alto nivel de incertidumbre. Los planes de estudio de las titulaciones que preparan a estos futuros ingenieros no pueden permanecer ajenos a estas necesidades y deben plantear situaciones lo más cercanas posible a la realidad que se encontrarán nuestros egresados en su vida laboral. Estas razones, nos han llevado a plantear una experiencia innovadora en una titulación de nueva implantación como es el Grado en Ingeniería Multimedia. Hemos elegido, para ello, la metodología del Aprendizaje Basado en Proyectos (ABP), aplicada al itinerario de Creación y Entretenimiento Digital en cuarto curso, donde los estudiantes, agrupados en equipos, desarrollan un único gran proyecto durante el año, que es un videojuego. Queremos destacar dos consecuencias de esta experiencia: primero, el papel fundamental de la asignatura Proyectos Multimedia, sirviendo de apoyo al resto de asignaturas al llevar el peso de la gestión de los equipos y del seguimiento del proyecto. Y después, que los estudiantes pueden obtener un producto terminado al final del curso que les permita inaugurar su portafolio profesional

Differential microRNA expression profile between stimulated PBMCs from HIV-1 infected elite controllers and viremic progressors

BACKGROUND: The emerging relationship between microRNAs (miRNA) and viral-control is a topic of interest in the field of HIV. Host-genome might play an important role in the control of viremia. The aim of this study was to assess the specific miRNA profile that could contribute to the control of HIV replication in Elite Controllers. RESULTS: After adequate normalization, expression profile of 286 human miRNAs (hsa-miR) was evaluated in phytohaemagglutinin-stimulated PBMCs from 29 individuals classified in 4 groups: 8 elite controllers (EC; viral load 5000 cp/ml without treatment), 8 patients under antiretroviral treatment (ART; VL<200 cp/ml) and 5 uninfected individuals (HIV-) through TaqMan Array Human microRNA Cards v3.0. A differential expression pattern consisting of 23 miRNAs became significantly different when comparing EC and VP. Profiling analysis segregated the population in two different blocks: while EC and HIV- clustered together in the same block (EC/HIV-_block 1), VP and ART individuals clustered together in a second block (VP/ART_block 2). Two inversely expressed miRNA patterns were determined within those two blocks: a set of 4 miRNAs (hsa-miR-221, -27a, -27b and -29b) was up-expressed in EC/HIV-_block and down-expressed in VP/ART_block while 19 miRNAs were down-expressed in block 1 and up-expressed in block 2. Differential miRNAs were successfully validated through individual RT-qPCR assays. CONCLUSIONS: Profile in EC resembled HIV- and differentially clusters with VP and ART. Therefore, differential clustering does not rely on undetectable viremia

Monitoring HIV viral load in resource limited settings: still a matter of debate?

Introduction Consequences of lack of viral monitoring in predicting the effects of development of HIV drug resistance mutations during HAART in resource-limited settings (RLS) is still a matter of debate. Design To assess, among HIV+ patients receiving their first-line HAART, prevalence of virological failure and genotypic resistance mutations pattern in a Médécins Sans Frontières/Ministry of Health programme in Busia District (Kenya). Methods Patients with HAART treatment for ≥12 months were eligible for the study and those with HIV-RNA ≥5000 copies/ml underwent genotypic study. Total HIV-1 RNA from Dried Blood Spots was extracted using Nuclisens method. Results 926 patients were included. Among 274 (29.6%) patients with detectable viral load, 55 (5.9%) experienced treatment failure (viral load >5.000 copies/ml); 61.8% were female and 10 (18.2%) had clinical failure. Median CD4 cell count was 116 cell/mm3 (IQR: 54-189). Median HIV-RNA was 32,000 copies/ml (IQR: 11000-68000). Eighteen out of 55 (33%) samples could be sequenced on PR and RT genes, with resistance associated mutations (RAMs) in 15 out of 18 samples (83%). Among patients carrying RAMs, 12/15 (81%) harboured RAMs associated to thymidine analogues (TAMs). All of them (100%) showed M184V resistance associated mutation to lamivudine as well as NNRTI's RAMS. Conclusions Virological failure rate in resource-limited settings are similar to those observed in developed countries. Resistance mutation patterns were concordant with HAART received by failing patients. Long term detectable viral load confers greater probability of developing resistance and as a consequence, making difficult to find out a cost-effective subsequent treatment regimen

Modelos mentales erróneos y persistentes en programación

El aprendizaje implica la creación de representaciones mentales análogas a lo aprendido, conocidas como modelos mentales. Estos modelos nos permiten realizar predicciones y tomar decisiones. Cuanto más cercanos sean a la realidad, mejores serán nuestras predicciones y decisiones, lo que indica que refinar estos modelos puede representar un aprendizaje efectivo. La programación, además, requiere realizar el proceso inverso: a partir de los efectos deseados, crear un programa que los produzca. Este proceso, más complejo que simplemente refinar un modelo mental, demanda múltiples modelos precisos y habilidad asociativa para navegar entre ellos en ambas direcciones. Los profesores enseñamos sobre modelos conceptuales, que son abstracciones claramente definidas. Adquirir estos modelos implica generalizar y extraer patrones de numerosos ejemplos específicos. A menudo, los modelos mentales iniciales se vinculan a detalles circunstanciales de los ejemplos, tanto al ruido como a la señal. Aunque estos modelos sean erróneos, pueden funcionar razonablemente bien en algunas situaciones específicas, ser suficientes para aprobar y persistir en el tiempo. Esto podría explicar dificultades futuras en la programación. Este estudio busca identificar modelos mentales incorrectos en la programación. Proponemos un método iterativo que parte de hipótesis basadas en la experiencia docente y llega hasta la evidencia empírica. Este enfoque también permite descubrir nuevos modelos y refinar nuestro conocimiento. Presentamos su aplicación con estudiantes de cuarto curso y conceptos de primer curso. Nuestros resultados destacan modelos erróneos potenciales y sugieren otros no previstos que requieren más investigación.Learning involves creating mental representations analogous to what is learned, known as mental models. These models allow us to make predictions and decisions. The closer they are to reality, the better our predictions and decisions will be, indicating that effective learning consists of refining these models. Programming, on the other hand, requires carrying out the reverse process: from the desired effects, create a program that produces them. This process, more complex than merely refining a mental model, demands multiple accurate models and associative skills to navigate between them in both directions. Teachers instruct on conceptual models, which are clearly defined abstractions. Acquiring these models involves generalizing and extracting patterns from numerous specific examples. Consequently, initial mental models often link to circumstantial details of the examples, both to the noise and the signal. Although these models may be erroneous, they can work reasonably well in some specific situations, be sufficient to pass, and persist over time. This could explain future difficulties in programming. This study seeks to identify incorrect mental models in programming. We propose an iterative method that starts from hypotheses based on teaching experience and reaches empirical evidence. This approach also allows discovering new models and refining our knowledge. We present its application with fourth-year students and first-year concepts. Our results highlight potential erroneous models and suggest other unforeseen ones that require further investigation.Este trabajo ha sido financiado por el Instituto de Ciencias de la Educación (ICE) de la Universidad de Alicante a través de su programa de ayudas Redes ICE de Investigación en Docencia Universitaria

HIV-1/HAART-Related Lipodystrophy Syndrome (HALS) Is Associated with Decreased Circulating sTWEAK Levels

Background and Objectives Obesity and HIV-1/HAART-associated lipodystrophy syndrome (HALS) share clinical, pathological and mechanistic features. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a multifunctional cytokine that plays an important role in obesity and related diseases. We sought to explore the relationship between HALS and circulating levels of soluble (s) TWEAK and its scavenger receptor sCD163. Methods This was a cross-sectional multicenter study of 120 HIV-1-infected patients treated with a stable HAART regimen; 56 with overt HALS and 64 without HALS. Epidemiological and clinical variables were determined. Serum levels of sTWEAK and sCD163 levels were measured by ELISA. Results were analyzed with Student's t-test, Mann-Whitney U and χ2 test. Pearson and Spearman correlation were used to estimate the strength of association between variables. Results Circulating sTWEAK was significantly decreased in HALS patients compared with non-HALS patients (2.81±0.2 vs. 2.94±0.28 pg/mL, p = 0.018). No changes were observed in sCD163 levels in the studied cohorts. On multivariate analysis, a lower log sTWEAK concentration was independently associated with the presence of HALS (OR 0.027, 95% CI 0.001-0.521, p = 0.027). Conclusions HALS is associated with decreased sTWEAK levels

Pharmacogenetics of efficacy and safety of HCV treatment in HCV-HIV coinfected patients: significant associations with IL28B and SOCS3 gene variants.

Background and Aims This was a safety and efficacy pharmacogenetic study of a previously performed randomized trial which compared the effectiveness of treatment of hepatitis C virus infection with pegylated interferon alpha (pegIFNα) 2a vs. 2b, both with ribavirin, for 48 weeks, in HCV-HIV coinfected patients. Methods The study groups were made of 99 patients (efficacy pharmacogenetic substudy) and of 114 patients (safety pharmacogenetic substudy). Polymorphisms in the following candidate genes IL28B, IL6, IL10, TNFα, IFNγ, CCL5, MxA, OAS1, SOCS3, CTLA4 and ITPA were assessed. Genotyping was carried out using Sequenom iPLEX-Gold, a single-base extension polymerase chain reaction. Efficacy end-points assessed were: rapid, early and sustained virological response (RVR, EVR and SVR, respectively). Safety end-points assessed were: anemia, neutropenia, thrombocytopenia, flu-like syndrome, gastrointestinal disturbances and depression. Chi square test, Student's T test, Mann-Whitney U test and logistic regression were used for statistic analyses. Results As efficacy is concerned, IL28B and CTLA4 gene polymorphisms were associated with RVR (p<0.05 for both comparisons). Nevertheless, only polymorphism in the IL28B gene was associated with SVR (p = 0.004). In the multivariate analysis, the only gene independently associated with SVR was IL28B (OR 2.61, 95%CI 1.2-5.6, p = 0.01). With respect to safety, there were no significant associations between flu-like syndrome or depression and the genetic variants studied. Gastrointestinal disturbances were associated with ITPA gene polymorphism (p = 0.04). Anemia was associated with OAS1 and CTLA4 gene polymorphisms (p = 0.049 and p = 0.045, respectively), neutropenia and thromobocytopenia were associated with SOCS3 gene polymorphism (p = 0.02 and p = 0.002, respectively). In the multivariate analysis, the associations of the SOCS3 gene polymorphism with neutropenia (OR 0.26, 95%CI 0.09-0.75, p = 0.01) and thrombocytopenia (OR 0.07, 95%CI 0.008-0.57, p = 0.01) remained significant. Conclusions In HCV-HIV coinfected patients treated with PegIFNα and ribavirin, SVR is associated with IL28B rs8099917 polymorphism. HCV treatment-induced neutropenia and thrombocytopenia are associated with SOCS3 rs4969170 polymorphism

La guía docente adaptada al modelo de Aprendizaje Basado en Proyectos: el informe previo

El proyecto de red para la evaluación de la implantación transversal de 4º del Grado en Ingeniería Multimedia en el itinerario de Creación y Entretenimiento digital tiene como objetivos la preparación y coordinación de las asignaturas para el desarrollo de una metodología de ABP, junto con la elaboración de las guías docentes de las asignaturas que conforman el itinerario. Uno de los apartados más importantes en la confección de dichas guías es el de la planificación docente. Conseguir que la programación de las clases sea adecuada y esté adaptada a la realidad del aula es uno de los retos más difíciles a los que nos enfrentamos los profesores del citado itinerario. Siguiendo los principios del ABP, se delegó en los estudiantes la responsabilidad de plantear el proyecto a realizar y su planificación, plasmándolo en un documento llamado informe previo que básicamente contiene una descripción detallada del problema a nivel profesional. En este trabajo presentamos las diversas experiencias desarrolladas en los 3 años de existencia del itinerario, que han ido modelando la estructura y contenidos del citado informe previo. También se muestra la evolución de los resultados de satisfacción con la metodología tanto de estudiantes como de profesores

Evaluación de la implantación transversal de 4º del grado en Ingeniería Multimedia, Itinerario Creación y Entretenimiento Digital

En esta memoria se describe el proyecto realizado para la evaluación de la implantación transversal del itinerario de Creación y Entretenimiento digital del cuarto curso del Grado en Ingeniería Multimedia de la Escuela Politécnica Superior, como continuación del planteamiento realizado en los proyectos anteriores de preparación, coordinación y seguimiento de las asignaturas del citado itinerario (identificadores 3013 y 3133). En el marco creado por los nuevos estudios dentro del EEES, el proyecto ha tenido como objetivos principales la preparación y coordinación de las asignaturas para el desarrollo de la metodología de Aprendizaje Basado en Proyectos (ABP), la elaboración de las fichas de las asignaturas y el ajuste de recursos disponibles y laboratorios. A partir de la experiencia adquirida en la planificación de cursos previos, se han elaborado las guías docentes de las asignaturas ajustando las del curso anterior. También se presentan los resultados obtenidos en la tercera experiencia llevada a cabo en este curso, expresados en el grado de satisfacción y las sugerencias y observaciones del alumnado y profesorado con la metodología ABP. Por último, se ha mantenido la página web informativa del itinerario creada el curso anterior, publicando noticias relacionadas y mejorando diversos aspectos

Water safety plan enhancements with improved drinking water quality detection techniques

Drinking water quality has been regulated in most European countries for nearly two decades by the drinking water directive 98/83/EC. The directive is now under revision with the goal of meeting stricter demands for safe water for all citizens, as safe water has been recognized as a human right by the United Nations. An important change to the directive is the implementation of a risk-based approach in all regulated water supplies. The European Union Framework Seventh Programme Aquavalens project has developed several new detection technologies for pathogens and indicators and tested them in water supplies in seven European countries. One of the tasks of the project was to evaluate the impact of these new techniques on water safety and on water safety management. Data were collected on risk factors to water safety for five large supplies in Denmark, Germany, Spain and the UK, and for fifteen small water supplies in Scotland, Portugal and Serbia, via a questionnaire aiming to ascertain risk factors and the stage of implementation of Water Safety Plans, and via site-specific surveys known as Sanitary Site Inspection. Samples were collected from the water supplies from all stages of water production to delivery. Pathogens were detected in around 23% of the 470 samples tested. Fecal contamination was high in raw water and even in treated water at the small supplies. Old infrastructure was considered a challenge at all the water supplies. The results showed that some of the technique, if implemented as part of the water safety management, can detect rapidly the most common waterborne pathogens and fecal pollution indicators and therefore have a great early warning potential; can improve water safety for the consumer; can validate whether mitigation methods are working as intended; and can confirm the quality of the water at source and at the tap