Rapid decrease in titer and breadth of neutralizing anti-HCV antibodies in HIV/HCV-coinfected patients who achieved SVR

Sustained virological response (SVR); Anti-HCV therapy; HIV/HCV-coinfected patientsRespuesta virológica sostenida (RVS); Terapia anti-VHC; Pacientes coinfectados por VIH/VHCResposta virològica sostinguda (RVS); Teràpia anti-VHC; Pacients infectats amb VIH/VHCThe main targets for neutralizing anti-hepatitis C virus (HCV) antibodies (HCV-nAbs) are the E1 and E2 envelope glycoproteins. We have studied the characteristics of HCV-nAbs through a retrospective study involving 29 HIV/HCV-coinfected patients who achieved sustained virological response (SVR) with peg-IFNα + ribavirin anti-HCV therapy. Plasma samples at baseline and week 24 after SVR were used to perform neutralization assays against five JFH1-based HCV recombinant viruses coding for E1 and E2 from genotypes 1a (H77), 1b (J4), 2a (JFH1), 3a (S52) and 4a (ED43). At baseline, the majority of plasma samples neutralized 1a, 1b, 2a, and 4a, but not 3a, genotypes. Twenty-four weeks following SVR, most neutralizing titers declined substantially. Furthermore, titers against 3a and 2a were not detected in many patients. Plasma samples with high HCV-nAb titers neutralized all genotypes, and the highest titers at the starting point correlated with the highest titers at week 24 after SVR. In conclusion, high titers of broad-spectrum HCV-nAbs were detected in HIV/HCV-coinfected individuals, however, those titers declined soon after SVR.The HIV BioBank, integrated in the Spanish AIDS Research Network, is supported by the Institute of Health Carlos III, ISCIII, Spanish Health Ministry (Grant nº RD06/0006/0035 and RD12/0017/0037) as part of the State Plan for Scientific and Technical Research and Innovation and co-financed by ISCIII- Sub-Directorate General for Research Assessment and Promotion and European Regional Development Fund (ERDF) and Foundation for Research and Prevention of AIDS in Spain (FIPSE). The RIS Cohort (CoRIS) is funded by the ISCIII through the Spanish AIDS Research Network (RIS C03/173 and RD12/0017/0018) as part of the State Plan for Scientific and Technical Research and Innovation and co-financed by ISCIII- Sub-Directorate General for Research Assessment and Promotion and European Regional Development Fund (ERDF). This study was supported by grants from Instituto de Salud Carlos III (ISCIII; grant numbers PI14/01094 and PI17/00657 to JB, PI17/00903 to JGG, PI14CIII/00011 and PI17CIII/00003 to SR) and Ministerio de Sanidad, Servicios Sociales e Igualdad (grant number EC11-241). The study was also funded by the RD16CIII/0002/0002, RD16/0025/0018, and RD16/0025/0017 projects as part of the Plan Nacional R + D + I and co-funded by ISCIII- Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER). JB is an investigator from the Programa de Intensificación de la Actividad Investigadora en el Sistema Nacional de Salud (I3SNS), Refs INT15/00079 and INT16/00100

Rapid decrease in titer and breadth of neutralizing anti-HCV antibodies in HIV/HCV-coinfected patients who achieved SVR

The main targets for neutralizing anti-hepatitis C virus (HCV) antibodies (HCV-nAbs) are the E1 and E2 envelope glycoproteins. We have studied the characteristics of HCV-nAbs through a retrospective study involving 29 HIV/HCV-coinfected patients who achieved sustained virological response (SVR) with pegIFNα+ribavirin anti-HCV therapy. Plasma samples at baseline and week 24 after SVR were used to perform neutralization assays against fve JFH1-based HCV recombinant viruses coding for E1 and E2 from genotypes 1a (H77), 1b (J4), 2a (JFH1), 3a (S52) and 4a (ED43). At baseline, the majority of plasma samples neutralized 1a, 1b, 2a, and 4a, but not 3a, genotypes. Twenty-four weeks following SVR, most neutralizing titers declined substantially. Furthermore, titers against 3a and 2a were not detected in many patients. Plasma samples with high HCV-nAb titers neutralized all genotypes, and the highest titers at the starting point correlated with the highest titers at week 24 after SVR. In conclusion, high titers of broad-spectrum HCV-nAbs were detected in HIV/HCV-coinfected individuals, however, those titers declined soon after SVRThis study was supported by grants from Instituto de Salud Carlos III (ISCIII; grant numbers PI14/01094 and PI17/00657 to JB, PI17/00903 to JGG, PI14CIII/00011 and PI17CIII/00003 to SR) and Ministerio de Sanidad, Servicios Sociales e Igualdad (grant number EC11-241). Te study was also funded by the RD16CIII/0002/0002, RD16/0025/0018, and RD16/0025/0017 projects as part of the Plan Nacional R+D+I and co-funded by ISCIII- Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER

New Adenovirus Groups in Western Palaearctic Bats

In the context of long-term screening for viruses on Western Palaearctic bats, we tested for the presence of adenovirus 1392 oropharyngeal swabs and 325 stool samples taken from 27 bat species. Adenoviruses were detected in 12 species of the Vespertilionidae and the Rhinolophidae families. Fifty positive respiratory and 26 positive stool samples were studied. Phylogenetic analyses of partial hexon protein and partial DNA-dependent DNA polymerase genes indicate that all these bat adenoviruses belong to the genus Mastadenovirus but without constituting a monophyletic cluster. According to genetic identities, the new groups are distinct to the previously described Bat mastadenovirus A and B species and contribute with potentially new members. Our data support that diversity of bat mastadenovirus is host-dependent and increase the knowledge of potentially pathogenic virus from bats. Due to the active role of bats as viral reservoirs, the characterization of these viruses is relevant for Public Health.This project was financially supported by an agreement between the Public Health Department of the Spanish Ministry of Health and the Instituto de Salud Carlos III for the development of "Rabies Surveillance in Spain" and by projects SAF 2006-12784-C02-01, SAF 2006-12784-C02-02, SAF 2009-09172 and SAF2013-47194-P of the General Research Programme of the Spanish Ministry of Science and Education

Protagonismo del mentor en una actividad tutorial de carácter multidisciplinar en Ingeniería

XIX Congreso Universitario de Innovación Educativa en las Enseñanzas Técnicas : Barcelona, 6 a 8 de julio de 2011En la Escuela Politécnica Superior (EPS) de la Universidad de Sevilla se ha trabajado, por tercer curso consecutivo, en un Plan de Acción Tutorial desarrollado por 16 profesores tutores y 20 alumnos mentores de 5 titulaciones de Ingeniería Técnica. El objetivo perseguido en este curso ha sido potenciar actividades que han surgido del propio albedrío de los alumnos mentores, lo que ha dado como resultado la realización de una serie de actividades de mentoría motivadas y dirigidas desde el principio por los alumnos mentores. La actividad conjunta de todos ellos ha llevado a organizar unos subgrupos de mentorías en función de determinadas características del alumnado de primer curso (deportistas, trabajadores, becarios de otras universidades…), a realizar reuniones presenciales de mentores para puesta a punto de estas actividades así como de puesta al día de los resultados que se iban consiguiendo, además de organizar una segunda captación de mentorizados tras las notas del primer cuatrimestre, y la protagonización de una Jornada de Mentoría al final del curso.A third edition with 16 tutorial lecturers and 20 tutorial students from five different degrees (Technical Engineering of the Polytechnical School, EPS, at University of Seville) in a Tutorial Plan development, has been prepared. During the present year, the main characteristic has been a serial of mentoring actions motivated and directed by these mentors. This activity has been organized considering several subgroups of mentoring depending on special characteristics in first year students (sportsplayers, workers, grant holders from other universities…), moreover the organization of a second recruiting of new students after the first term marks, updating meetings for mentors only, and to be main figures in a Congress on Mentoring at the end of the academic year

Genetic Structure of the Spanish Population

<p>Abstract</p> <p>Background</p> <p>Genetic admixture is a common caveat for genetic association analysis. Therefore, it is important to characterize the genetic structure of the population under study to control for this kind of potential bias.</p> <p>Results</p> <p>In this study we have sampled over 800 unrelated individuals from the population of Spain, and have genotyped them with a genome-wide coverage. We have carried out linkage disequilibrium, haplotype, population structure and copy-number variation (CNV) analyses, and have compared these estimates of the Spanish population with existing data from similar efforts.</p> <p>Conclusions</p> <p>In general, the Spanish population is similar to the Western and Northern Europeans, but has a more diverse haplotypic structure. Moreover, the Spanish population is also largely homogeneous within itself, although patterns of micro-structure may be able to predict locations of origin from distant regions. Finally, we also present the first characterization of a CNV map of the Spanish population. These results and original data are made available to the scientific community.</p

Enhancing SARS-CoV-2 Surveillance through Regular Genomic Sequencing in Spain: The RELECOV Network

Millions of SARS-CoV-2 whole genome sequences have been generated to date. However, good quality data and adequate surveillance systems are required to contribute to meaningful surveillance in public health. In this context, the network of Spanish laboratories for coronavirus (RELECOV) was created with the main goal of promoting actions to speed up the detection, analyses, and evaluation of SARS-CoV-2 at a national level, partially structured and financed by an ECDC-HERA-Incubator action (ECDC/GRANT/2021/024). A SARS-CoV-2 sequencing quality control assessment (QCA) was developed to evaluate the network’s technical capacity. QCA full panel results showed a lower hit rate for lineage assignment compared to that obtained for variants. Genomic data comprising 48,578 viral genomes were studied and evaluated to monitor SARS-CoV-2. The developed network actions showed a 36% increase in sharing viral sequences. In addition, analysis of lineage/sublineage-defining mutations to track the virus showed characteristic mutation profiles for the Delta and Omicron variants. Further, phylogenetic analyses strongly correlated with different variant clusters, obtaining a robust reference tree. The RELECOV network has made it possible to improve and enhance the genomic surveillance of SARS-CoV-2 in Spain. It has provided and evaluated genomic tools for viral genome monitoring and characterization that make it possible to increase knowledge efficiently and quickly, promoting the genomic surveillance of SARS-CoV-2 in Spain

Vertidos tóxicos al río Guadiamar: propuestas técnicas para su corrección

Inmediatamente de producirse el vertido tóxico al río Guadiamar, el Grupo T.A.R. se lanzó sin pensarlo dos veces a la búsqueda de soluciones técnicas a un panorama desolador y de efectos desconocidos, todos ellos amenazantes. El ácido “se comía el suelo inundado” por la riada, el agua retenida en Entremuros a pH 3, y con un enorme contenido de metales pesados, ocupaba una extensión de kilómetros. Nos hundimos en el agua hasta el cuello, y cuando nos cubría cogimos la barca, metimos el río a pedazos en nuestro laboratorio, para trabajar todas las hipótesis, ensayar todas las posibilidades. Peleando con la realidad le sacamos datos al Guadiamar, diseñamos actuaciones, poniéndole ingeniería a cuantas hipótesis nos planteaba la situación. En primera fila observamos las mejores actuaciones que nadie diseñó. El propio río, activando sus defensas naturales, mejoró la calidad del agua retenida en el dique de Entremuros subiendo el pH y precipitando los metales pesados. Los mecanismos de entrada de los metales pesados en la cadena trófica parecían ser lentos, dando tiempo a que la retirada de los lodos tóxicos llevada a cabo por la Administración fuera eficaz y diera tiempo a realizar tanto esfuerzo. Aunque el Guadiamar ha trabajado muy duro en su propia recuperación, con su ayuda hemos elaborado una gran cantidad de propuestas técnicas; unas para actuaciones de emergencia, otras a corto, medio y largo plazo. También hemos dado forma a un Plan frente a las previsibles avenidas de este primer otoño después del vertido. Nuestro objetivo ha sido poner a disposición soluciones preparadas para todo tipo de problemas, en primera o en segunda instancia. Prevenir no solo una o dos contingencias, se ha tratado de estar preparado para la mayor cantidad de eventualidades posibles. Por ello algunas serán utilizables, otras estarán en reserva, y muchas irían al cajón de los papeles. Pero ahí están por si acaso. Este libro recoge los trabajos de campo, los ensayos de laboratorio y la ingeniería desarrollada en los primeros cuatro meses. Durante el siguiente preparamos la edición del mismo, mientras, en paralelo, continuábamos en el trabajo experimental y el diseño. Cuando se cumpla el quinto mes, el 25 de Septiembre de 1998, lo presentaremos, ciento cincuenta días después... Con la financiación de la Diputación de Sevilla hemos preparado la primera edición en formato CD Rom e Internet, con muy poco coste para acceder a su contenido. En poco tiempo saldrá la edición en papel, con la misma financiación que la primera. Nos gustaría que este documento fuera entendido como lo que es, en nuestra opinión, una llamada urgente al debate de las ideas. Tratamos de ofrecer la información necesaria y el foro donde recoger las propuestas que seguramente muchos pueden aportar sin saber como transmitir sus experiencias. El Grupo de Tratamiento de Aguas Residuales (T.A.R.) abre con este libro la MESA DE DISCUSIÓN, para buscar un poco de luz, avanzar en las soluciones técnicas a la inmensa tarea de recuperar el río Guadiamar. El libro presenta lagunas, unas por la enorme prisa, otra por falta de datos, muchas por nuestra escasez de conocimientos. Dicen en España que “lo mejor es enemigo de lo bueno”...,y nos gustaría recoger ideas hoy mejor que mañana, que podría ser tarde. Nos comprometemos a seguir trabajando en soluciones técnicas, innovaciones tecnológicas e investigación aplicada a la recuperación del Guadiamar, a conocer lo ocurrido y su remedio. Nos comprometemos a publicar de la misma forma los resultados obtenidos, de manera que la discusión y el debate sigan siempre abiertos. El grupo T.A.R. podría ser un punto de intercambio de conocimientos universal, abierto, respetuoso y tolerante, universitario en definitiva, y por tanto útil en el cumplimiento de sus obligaciones. La primera necesidad de responder urgentemente, está dando paso a unas actuaciones programadas, a medida de los efectos de las correcciones introducidas. Deben instaurarse políticas de prevención y nuevas actuaciones para recuperar el Guadiamar, mejorar urgentemente las condiciones del entorno. Aprender de las soluciones adoptadas y generar mejores prácticas, puede ser una buena conclusión del trabajo realizado por tanta gente. Lo que empezó siendo una carrera de velocidad se nos convierte en un maratón, ya no hay que correr explosivamente, hay que mantener un ritmo en la carrera; hay que persistir en el esfuerzo todos los días durante mucho tiempo. Este nuevo desafío sigue siendo duro y difícil. Podéis contar con el Grupo T.A.R. para recorrer el duro camino de la Recuperación

A colorectal cancer susceptibility new variant at 4q26 in the Spanish population identified by genome-wide association analysis

BACKGROUND: Non-hereditary colorectal cancer (CRC) is a complex disorder resulting from the combination of genetic and non-genetic factors. Genome-wide association studies (GWAS) are useful for identifying such genetic susceptibility factors. However, the single loci so far associated with CRC only represent a fraction of the genetic risk for CRC development in the general population. Therefore, many other genetic risk variants alone and in combination must still remain to be discovered. The aim of this work was to search for genetic risk factors for CRC, by performing single-locus and two-locus GWAS in the Spanish population. RESULTS: A total of 801 controls and 500 CRC cases were included in the discovery GWAS dataset. 77 single nucleotide polymorphisms (SNP)s from single-locus and 243 SNPs from two-locus association analyses were selected for replication in 423 additional CRC cases and 1382 controls. In the meta-analysis, one SNP, rs3987 at 4q26, reached GWAS significant p-value (p = 4.02×10(-8)), and one SNP pair, rs1100508 CG and rs8111948 AA, showed a trend for two-locus association (p = 4.35×10(-11)). Additionally, our GWAS confirmed the previously reported association with CRC of five SNPs located at 3q36.2 (rs10936599), 8q24 (rs10505477), 8q24.21(rs6983267), 11q13.4 (rs3824999) and 14q22.2 (rs4444235). CONCLUSIONS: Our GWAS for CRC patients from Spain confirmed some previously reported associations for CRC and yielded a novel candidate risk SNP, located at 4q26. Epistasis analyses also yielded several novel candidate susceptibility pairs that need to be validated in independent analyses

Using Interpretable Machine Learning to Identify Baseline Predictive Factors of Remission and Drug Durability in Crohn’s Disease Patients on Ustekinumab

Ustekinumab has shown efficacy in Crohn's Disease (CD) patients. To identify patient profiles of those who benefit the most from this treatment would help to position this drug in the therapeutic paradigm of CD and generate hypotheses for future trials. The objective of this analysis was to determine whether baseline patient characteristics are predictive of remission and the drug durability of ustekinumab, and whether its positioning with respect to prior use of biologics has a significant effect after correcting for disease severity and phenotype at baseline using interpretable machine learning. Patients' data from SUSTAIN, a retrospective multicenter single-arm cohort study, were used. Disease phenotype, baseline laboratory data, and prior treatment characteristics were documented. Clinical remission was defined as the Harvey Bradshaw Index <= 4 and was tracked longitudinally. Drug durability was defined as the time until a patient discontinued treatment. A total of 439 participants from 60 centers were included and a total of 20 baseline covariates considered. Less exposure to previous biologics had a positive effect on remission, even after controlling for baseline disease severity using a non-linear, additive, multivariable model. Additionally, age, body mass index, and fecal calprotectin at baseline were found to be statistically significant as independent negative risk factors for both remission and drug survival, with further risk factors identified for remission

Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn’s Disease Patients: The SUSTAIN Study

Background Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn’s disease (CD) patients in real-world clinical practice. Methods A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≥1 intravenous dose of ustekinumab for ≥6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety. Results A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≥3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≥1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required dose escalation or intensification; of these, 24.8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever). Conclusions Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice