Drug resistance mutations in HIV-2 patients failing raltegravir and influence on dolutegravir response

Producción CientíficaBackground: A broader extent of amino acid substitutions in the integrase of HIV-2 compared with HIV-1 might enable greater cross-resistance between raltegravir and dolutegravir in HIV-2 infection. Few studies have examined the virological response to dolutegravir in HIV-2 patients that failed raltegravir. Methods: All patients recorded in the HIV-2 Spanish cohort were examined. The integrase coding region was sequenced in viraemic patients. Changes associated with resistance to raltegravir and dolutegravir in HIV-1 were recorded. Results: From 319 HIV-2-infected patients recorded in the HIV-2 Spanish cohort, 53 integrase sequences from 30 individuals were obtained (20 raltegravir naive and 10 raltegravir experienced). Only one secondary mutation (E138A) was found in one of the 20 raltegravir-naive HIV-2 patients. For raltegravir-experienced individuals, the resistance mutation profile in 9 of 10 viraemic patients was as follows: N155H + A153G/S (four); Y143G + A153S (two); Q148R + G140A/S (two); and Y143C + Q91R (one). Of note, all patients with Y143G and N155H developed a rare non-polymorphic mutation at codon 153. Rescue therapy with dolutegravir was given to 5 of these 10 patients. After >6 months on dolutegravir therapy, three patients with baseline N155H experienced viral rebound. In two of them N155H was replaced by Q148K/R and in another by G118R. Conclusions: A wide repertoire of resistance mutations in the integrase gene occur in HIV-2-infected patients failing on raltegravir. Although dolutegravir may allow successful rescue in most HIV-2 raltegravir failures, we report and characterize three cases of dolutegravir resistance in HIV-2 patients, emerging variants Q148K and Q148R and a novel change G118R.Fondo de Investigación Sanitaria-Fondos FEDER (FIS, PI13/01574; ICI14/0274, CES12/003, FI14/00264, CD14/00243

Successful Direct Acting Antiviral Therapy in ChronicHepatitis C Normalizes IFN and IL2 Production in T Cells Together with TLR8 Expression and Functionality in Peripheral Blood Mononuclear Cells

Chronic hepatitis C infection (HCV) activates a systemic cell-mediated immune response characterized by the production of IFN? and an innate immune response addressed by the activation of TLR signaling. We aimed to investigate whether HCV eradication by direct acting antivirals (DAA) leads to a recovery in cell-mediated immune response and TLR expression and functionality. Blood samples were obtained in HCV infected patients before DAA treatment and at week +48 after the end of treatment. Results were compared to healthy controls. Cell surface expression of TLR8 was assessed on peripheral blood mononuclear cells (PBMCs) by flow cytometry. Freshly isolated PBMCs were cultured with specific TLR8 agonists and intracellular production of cytokines was determined by flow-cytometry after ex vivo TLR8 activation with ssRNA 40. Production of IFN?, IL2 and IL17 was assessed by flow cytometry in T cells after polyclonal activation. Included were 50 HCV-infected patients and 15 controls. TLR8 expression in PBMCs was significantly increased before treatment and recovered normal levels at week +48. Production of IL1b, IL6 and TNF? dependent on the activation of TLR8 in PBMCs was also increased in patients before DAA treatment, with a significant reduction at week +48. Combined expression of IFN? and IL2 in CD4+ T cells in HCV-infected patients was significantly increased compared to controls and recovered normal levels at week +48. DAA-mediated clearance of HCV is associated with a decreased expression and activation of TLR8 in PBMCs until healthy control levels which is accompanied by a reduction in the Th1 response.This research was funded by the Instituto de Salud Carlos III (ISCIII), grant number PIE15/00079

Plan de Acción Tutorial Integrado, en Educación

En el proyecto que se presenta se parte no solamente de una amplia trayectoria de los Grados de la Facultad de Ciencias de la Educación de la UGR en orientación universitaria, sino, además, de una necesidad patente plasmada en los Objetivos Estratégicos que se incluyen dentro del Sistema para la Garantía de la Calidad de la Facultad; siendo el segundo objetivo “Orientación y tutoría académica”, y una de sus acciones (Plan Director 19-21): Crear curriculum complementario para los estudiantes (desarrollo de competencias transversales a través de un PAT). Otras acciones relacionadas y en las que continuamos trabajando en el Plan Director 22 24 son Establecer acciones de tutorización coordinadas y complementarias al PAT, formar a los tutores de grupo-curso, establecer un plan general de orientación profesional y empleabilidad, potenciar la orientación académica y profesional de los estudiantes NEAE, entre otras. Con el diseño del Plan de Acción Tutorial Integrado, en Educación, se pretende desarrollar en el estudiantado de los Grados en Pedagogía, Ed. Social, Ed. Infantil y Ed. Primaria, competencias transversales que complementen su formación académica y le ayuden en su desarrollo académico, personal y profesional. En él participará profesorado, alumnado y PAS de la Facultad, no solamente para fomentar su sentimiento de pertenencia y favorecer un clima de comunidad universitaria, sino además, para enriquecerse unos a otros, aprendiendo juntos, solventando dudas, guiando, orientando y haciendo que el paso por la Universidad de todo el alumnado que participe del mismo, sea lo más enriquecedor y productivo posible, logrando un elevado rendimiento académico, un adecuado desarrollo personal y un posterior futuro profesional colmado de éxitos. Para ello se ha llevado a cabo un análisis de necesidades mediante el Cuestionario para detección de necesidades formativas transversales del alumnado en la Facultad de Ciencias de la Educación (Escala de competencias transversales del cuestionario CECTGRA de Martínez y González, 2018), a partir del cual se diseñan diferentes talleres orientados a cada curso según sus intereses, motivaciones y necesidades, haciendo una posterior evaluación de los resultados y un análisis de los mismos. Se ha logrado además del diseño del PAT, dotar de unidad a todas las actividades que desde la Facultad se realizaban en torno a la orientación del estudiantado. Se ha realizado un esfuerzo porque los resultados obtenidos se vean reflejados en las diferentes materias, no solamente a nivel transversal sino de forma directa. Por ejemplo, al trabajarse la normativa APA se ha introducido este punto en las rúbricas de evaluación de diferentes asignaturas para, de este modo, relacionar su aprendizaje con la evaluación y rendimiento académico. Al centrarse el primer curso fundamentalmente en el análisis de necesidades, la asistencia ha sido mucho mayor en el segundo curso (21-22), haciendo especial hincapié en la difusión de las actividades, siguiendo el Plan de Comunicación del Centro, a través de la web de la Facultad y de la figura de los tutores de grupo curso. Un objetivo a largo plazo, es incluir las competencias aprendidas en los talleres dirigidos al estudiantado de 4º en la calificación del Trabajo Fin de Grado. Este punto no ha dado tiempo a consolidarlo en dos cursos académicos, pero seguiremos trabajando en ello ya que consideramos que es fundamental además de poder dar de esta forma respuesta a una de las alegaciones realizadas por la DEVA en el informe de la renovación de la acreditación de los Grados.This project is based not only on a wide trajectory of the Degrees of the Faculty of Education Sciences of the UGR in university orientation, but, in addition, from a patent need embodied in the Strategic Objectives that are included within the System for the Guarantee of the Quality of the Faculty; the second objective being "Academic guidance and tutoring", and one of its actions (Master Plan 19-21): Create complementary curriculum for students (development of transversal competences through a PAT). Other related actions and in which we continue to work in the Master Plan 22 24 are To establish coordinated and complementary tutoring actions to the PAT, to train the group-course tutors, to establish a general plan of professional orientation and employability, to enhance the academic and professional orientation of the NEAE students, among others. With the design of the Integrated Tutorial Action Plan, in Education, it is intended to develop in the students of the Degrees in Pedagogy, Social Ed., Infant Ed. and Primary Ed., transversal competences that complement their academic training and help them in their academic, personal and professional development. It will involve teachers, students and PAS of the Faculty, not only to promote the feeling of belonging of the same and favor a climate of university community, but, in addition, to enrich each other, learning together, solving doubts, guiding, guiding and making the passage through the University of all the students who participate in it, as enriching and productive as possible, achieving a high academic performance, a competent personal development and a subsequent professional future full of successes. To this end, a needs analysis has been carried out (through the Questionnaire for the detection of transversal training needs of students in the Faculty of Education Sciences (Scale of transversal competences of the CECTGRA questionnaire of Martínez y González, 2018), reflected in different workshops oriented to each course according to their interests, motivations and needs, making a subsequent evaluation of the results and analysis of them. It has been achieved in addition to the design of the PAT, to provide unity to all the activities that from the Faculty were carried out around the orientation of the students. We have worked so that the results obtained are reflected in the different subjects, not only at a transversal level but directly. For example, when working on the APA regulations, it has been introduced in the evaluation rubrics of different subjects in order to relate their learning with evaluation and academic performance. By focusing the first course mainly on the analysis of needs, the attendance has been much higher in the second year (21 22), with special emphasis on the dissemination of the activities, following the Communication Plan of the Center, through the website of the Faculty and the figure of the tutors of the course group. A long-term objective is to include the skills learned in the workshops of the 4th grade students in the TFG qualification. This point has not given time to consolidate it in two academic years but we will continue working on it since we consider that it is fundamental in addition to being able to respond in this way to one of the allegations made by the DEVA in the report of the renewal of the accreditation of the Degrees.Unidad de Calidad, Innovación Docente y Prospectiva. Universidad de Granada

Use of tocilizumab in kidney transplant recipients with COVID-1

Acute respiratory distress syndrome associated with coronavirus infection is related to a cytokine storm with large interleukin-6 (IL-6) release. The IL-6-receptor blocker tocilizumab may control the aberrant host immune response in patients with coronavirus disease 2019 (COVID-19) . In this pandemic, kidney transplant (KT) recipients are a high-risk population for severe infection and showed poor outcomes. We present a multicenter cohort study of 80 KT patients with severe COVID-19 treated with tocilizumab during hospital admission. High mortality rate was identified (32.5%), related with older age (hazard ratio [HR] 3.12 for those older than 60 years, P = .039). IL-6 and other inflammatory markers, including lactic acid dehydrogenase, ferritin, and D-dimer increased early after tocilizumab administration and their values were higher in nonsurvivors. Instead, C-reactive protein (CRP) levels decreased after tocilizumab, and this decrease positively correlated with survival (mean 12.3 mg/L in survivors vs. 33 mg/L in nonsurvivors). Each mg/L of CRP soon after tocilizumab increased the risk of death by 1% (HR 1.01 [confidence interval 1.004-1.024], P = .003). Although patients who died presented with worse respiratory situation at admission, this was not significantly different at tocilizumab administration and did not have an impact on outcome in the multivariate analysis. Tocilizumab may be effective in controlling cytokine storm in COVID-19 but randomized trials are needed

Monitorización y seguimiento del esfuerzo realizado por los estudiantes y de su asistencia a actividades presenciales

Este artículo documenta el planteamiento, la metodología y los primeros resultados de un plan de monitorización detallada del esfuerzo y de asistencia a actividades presenciales por parte de los estudiantes de las titulaciones ofertadas por la Escuela Técnica Superior de Ingenieros Navales de la Universidad Politécnica de Madrid durante el segundo cuatrimestre del curso 2011-2012. Se ha establecido un sistema mecánico de recogida de datos de esfuerzo por parte de los estudiantes utilizando una hoja tipo test especialmente configurada al efecto. Se pasa una hoja en todas y cada una de las actividades presenciales realizadas y en la hoja se solicita información sobre el trabajo "fuera de clase". Se documenta en este artículo cómo se ha estructurado esa hoja, qué tipo de datos se recogen, cómo se tratan mediante una base de datos creada al efecto, qué tipo de análisis se puede realizar y qué resultados preliminares obtenemos de dichos análisis

Oral saliva swab reverse transcription PCR for Covid-19 in the paediatric population

8Pág. Centro de Investigación en Sanidad Animal (CISA)To evaluate the performance of oral saliva swab (OSS) reverse transcription PCR (RT-PCR) compared with RT-PCR and antigen rapid diagnostic test (Ag-RDT) on nasopharyngeal swabs (NPS) for SARS-CoV-2 in children.The study was funded by: Project PI20/00095, from the Instituto de Salud Carlos III (Ministry of Economy, Industry and Competitiveness) and cofounded by the European Regional Development Fund, by Infanta Sofia University Hospital and Henares University Hospital Foundation for Biomedical Research and Innovation (FIIB HUIS HHEN), and by SERMAS-Fundación para la Investigación Biomédica del Hospital 12 de Octubre. EC-C is supported by the Spanish Society of Paediatrics (Asociación Española de Pediatría); Grant COVID-19 EPICO-AEP 2020. JMM is funded by SERMAS-Fundación para la Investigación Biomédica del Hospital Infanta Sofía y del Henares and by Universidad Europea de Madrid, Spain. MdlS is funded by Grant Cantera de Investigación Santander, Fundación Universidad Europea de Madrid, Spain. ED is funded by the Juan de la Cierva–Incorporación granted by the Spanish Ministry of Science and Innovation. DB-G is funded by the Spanish Ministry of Science and Innovation—Instituto de Salud Carlos III and Fondos FEDER by ’Contratos para la intensificación de la actividad investigadora en el Sistema Nacional de Salud, 2020 (INT20/00086)’.Peer reviewe

CARB-ES-19 Multicenter Study of Carbapenemase-Producing Klebsiella pneumoniae and Escherichia coli From All Spanish Provinces Reveals Interregional Spread of High-Risk Clones Such as ST307/OXA-48 and ST512/KPC-3

ObjectivesCARB-ES-19 is a comprehensive, multicenter, nationwide study integrating whole-genome sequencing (WGS) in the surveillance of carbapenemase-producing K. pneumoniae (CP-Kpn) and E. coli (CP-Eco) to determine their incidence, geographical distribution, phylogeny, and resistance mechanisms in Spain.MethodsIn total, 71 hospitals, representing all 50 Spanish provinces, collected the first 10 isolates per hospital (February to May 2019); CPE isolates were first identified according to EUCAST (meropenem MIC > 0.12 mg/L with immunochromatography, colorimetric tests, carbapenem inactivation, or carbapenem hydrolysis with MALDI-TOF). Prevalence and incidence were calculated according to population denominators. Antibiotic susceptibility testing was performed using the microdilution method (EUCAST). All 403 isolates collected were sequenced for high-resolution single-nucleotide polymorphism (SNP) typing, core genome multilocus sequence typing (cgMLST), and resistome analysis.ResultsIn total, 377 (93.5%) CP-Kpn and 26 (6.5%) CP-Eco isolates were collected from 62 (87.3%) hospitals in 46 (92%) provinces. CP-Kpn was more prevalent in the blood (5.8%, 50/853) than in the urine (1.4%, 201/14,464). The cumulative incidence for both CP-Kpn and CP-Eco was 0.05 per 100 admitted patients. The main carbapenemase genes identified in CP-Kpn were blaOXA–48 (263/377), blaKPC–3 (62/377), blaVIM–1 (28/377), and blaNDM–1 (12/377). All isolates were susceptible to at least two antibiotics. Interregional dissemination of eight high-risk CP-Kpn clones was detected, mainly ST307/OXA-48 (16.4%), ST11/OXA-48 (16.4%), and ST512-ST258/KPC (13.8%). ST512/KPC and ST15/OXA-48 were the most frequent bacteremia-causative clones. The average number of acquired resistance genes was higher in CP-Kpn (7.9) than in CP-Eco (5.5).ConclusionThis study serves as a first step toward WGS integration in the surveillance of carbapenemase-producing Enterobacterales in Spain. We detected important epidemiological changes, including increased CP-Kpn and CP-Eco prevalence and incidence compared to previous studies, wide interregional dissemination, and increased dissemination of high-risk clones, such as ST307/OXA-48 and ST512/KPC-3

Cuentos de nunca acabar. Aproximaciones desde la interculturalidad

Cuentos de nunca acabar. Aproximaciones desde la interculturalidad, surge después de la pandemia y su imposibilidad de socializar “en persona” con los compañeros de eventuales encuentros, porque la Comprensión Lectora tenía que reinventarse para su nueva reflexión cognitiva, adaptación contextual y reconstrucción del conocimiento. Este renovado enfoque de la realidad postpandemia, concebido en el marco de la educación intercultural comunitaria, busca potencializar los entornos naturales, sociales y culturales como recursos de aprendizaje multidisciplinario a través del lenguaje animado de los cuentos. En este marco, había que dinamizar la asignatura de Comunicación Oral y Escrita, que se dicta en los Primeros Niveles de los Centros de Apoyo de Otavalo, Cayambe, Latacunga y Riobamba, mediante un eje transversal donde los estudiantes escriban fundamentados en valores de la cosmovisión andina, considerando que provienen de varios lugares de la sierra y amazonía ecuatoriana. Todo surgió del encuentro presencial de un sábado cualquiera donde los estudiantes realizaban ejercicios narrativos, logrando una apreciable respuesta de imaginación, más emotiva que la clásica tarea de las Unidades, tanto así que, pasados unos días, seguían llegando sus escritos a mi correo. Entonces nos pusimos manos a la obra, cada estudiante tendría dos opciones como Actividad Integradora, la primera consistía en escribir un cuento de su propia inspiración, y la segunda analizar un clásico para comentar sus valores y antivalores. La mayor parte de estudiantes decidió escribir su propio cuento, de donde se escogieron algunas participaciones que podrían considerarse originales, para una edición que, respetando la transcripción de la tradición oral que prima en los sectores comunitarios, nos concretamos en revisar la puntuación y ortografía para publicarlos. Con esto buscamos innovar la Actividad Integradora, por algo más práctico y operativo para configurar los Objetos de Aprendizaje que buscamos. Así nació, en medio del camino, este libro de Cuentos de nunca acabar. Aproximaciones desde la interculturalidad, que ponemos en sus manos. Hernán Hermosa Mantilla Quito, junio de 202