HERVs in Multiple Sclerosis — From Insertion to Therapy

Genome-wide association studies (GWAS) have not been able to completely elucidate the genetic background of complex diseases. Part of it could lie in repetitive sequences not studied in the GWAS, as those corresponding to Human Endogenous Retroviruses (HERVs). In the present work, we aim to review the potential role of HERVs in the etiology of autoimmune diseases, especially in multiple sclerosis (MS); their potential pathogenic role and their putative consideration as a good target for new treatments. For this purpose, we carried out an in-depth literature review on HERVs, and we integrated our previous findings about HERV-W, HERV-K18, and HERV-Fc1 and MS susceptibility. The study was carried out by a systematic search from electronic databases using the keywords “HERV,” “Multiple sclerosis,” “HERV-W,” “MSRV,” “HERV-K,” “HERV-Fc1,” and “GNbAC1.

Esclerosis múltiple: encrucijada entre genética, inmunología y virología

La esclerosis múltiple (EM) es una enfermedad crónica progresiva caracterizada por inflamación en el sistema nervioso central acompañado por desmielinización, daño axonal y disfunción neurológica progresiva. Se trata de una enfermedad compleja, cuya incidencia parece haber incrementado en los últimos tiempos, afectando actualmente a 2.3 millones de personas en el mundo. Sin embargo, muchos de los aspectos de su etiopatogenia continúan sin ser conocidos hoy en día. Es comúnmente aceptado que surge de la interacción de una serie de factores ambientales en individuos genéticamente susceptibles. Los estudios de barrido genómicos (GWAS) junto con el proyecto InmunoChip han permitido identificar un total de 110 polimorfismos de un solo nucleótido (SNPs) asociados con la susceptibilidad a desarrollar EM. Pero la realidad es que, a excepción del HLA-DRB1*15:01, cada uno de ellos posee un efecto modesto, por lo que el conjunto solo es capaz de explicar de un 20 a un 28% del riesgo recurrente en hermanos, quedando todavía una gran parte de la heredabilidad sin explicar. Los retrovirus endógenos humanos (HERVs) son “parásitos genéticos” del genoma de los vertebrados. Provienen de una infección ancestral por retrovirus exógenos, que tras infectar la línea germinal del individuo y sufrir un proceso de endogenización, han pasado a heredarse de forma mendeliana. Actualmente componen el 8% del genoma humano. Normalmente no se expresan porque consisten en copias defectivas o inactivas, sin embargo, se ha observado una reactivación de HERVs específicos asociada con varios tipos de cáncer, enfermedades autoinmunes como la EM, la artritis reumatoide (AR), la psoriasis o el lupus eritematoso sistémico; y otras enfermedades como la esquizofrenia. MSRV (Multiple sclerosis associated-retrovirus), fundador de la familia HERV-W, es el retrovirus endógeno asociado de manera más notable a la EM. Desde que se descubriese en 1989, son muchos los estudios que lo relacionan con la enfermedad: se ha descrito la presencia de la proteína Env de tipo MSRV en lesiones desmielinizantes agudas de pacientes con EM, así como un mayor número de copias de ADN o una alta prevalencia de secuencias de ARN de tipo MSRV en el suero y líquido cefalorraquídeo (LCR) de pacientes con EM comparado con pacientes de otras enfermedades neurológicas o controles de todos los grupos étnicos. Además, la presencia de MSRV en suero y LCR correlaciona con la progresión clínica, severidad y prognosis de la enfermedad. Pese a ello, su origen cromosómico está aún por determinar..

Peer tutoring of computer programming increases exploratory behavior in children

There is growing interest in teaching computer science and programming skills in schools. Here we investigated the efficacy of peer tutoring, which is known to be a useful educational resource in other domains but never before has been examined in such a core aspect of applied logical thinking in children. We compared (a) how children (N = 42, age range = 7 years 1 month to 8 years 4 months) learn computer programming from an adult versus learning from a peer and (b) the effect of teaching a peer versus simply revising what has been learned. Our results indicate that children taught by a peer showed comparable overall performance—a combination of accuracy and response times—to their classmates taught by an adult. However, there was a speed–accuracy trade-off, and peer-taught children showed more exploratory behavior, with shorter response times at the expense of lower accuracy. In contrast, no tutor effects (i.e., resulting from teaching a peer) were found. Thus, our results provide empirical evidence in support of peer tutoring as a way to help teach computer programming to children. This could contribute to the promotion of a widespread understanding of how computers operate and how to shape them, which is essential to our values of democracy, plurality, and freedom.Fil: de la Hera, Diego Pablo. Universidad Torcuato Di Tella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Zanoni Saad, María Belén. Universidad Torcuato Di Tella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sigman, Mariano. Universidad Torcuato Di Tella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Calero, Cecilia Ines. Universidad Torcuato Di Tella; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Encuesta sobre las perspectivas de futuro de los alumnos que están cursando Bachillerato. Curso 2012/2013

El estudio que se presenta a continuación resume el trabajo realizado para conocer el interés de los estudiantes de bachillerato de Palencia, Segovia, Soria y Valladolid, que constituyen el distrito de la Universidad de Valladolid, por la continuación de sus estudios en alguno de los distintos grados universitarios y sus posibles salidas profesionales, enmarcando este posible interés con algunos aspectos de su situación social. El trabajo se ha realizado en varias fases, todas ellas de interés en sí mismas, como son, la recogida de información pertinente para establecer el marco de actuación, así como la estratificación necesaria para realizar el muestreo, la elaboración de un cuestionario que permita analizar las características consideradas de mayor interés en el estudio, la puesta en marcha de un procedimiento informático que agilice la respuesta al cuestionario y la recogida de la información, la creación de un diseño muestral acorde con la estratificación, que garantice el cumplimiento con unos errores de muestreo prefijados, la realización del trabajo de campo acudiendo a una mayoría de centros para apoyar a los profesores consiguiendo una óptima realización de la encuesta por los estudiantes, la depuración de la base de datos y por último la realización de algunos análisis, aún parciales, sobre los datos recogidos, así como su presentación en la presente memoria. La población con la que se va a trabajar cuenta con un total de 11276 alumnos que estudian bachillerato en alguno de los 102 colegios o institutos de las provincias de Palencia, Segovia, Soria y Valladolid. La muestra seleccionada de acuerdo al diseño muestral establecido consta finalmente de 2066 estudiantes de 24 centros. Se estima que el 55,5% de los alumnos de bachillerato está satisfecho o muy satisfecho con sus resultados escolares; el 67,4% lo está con la formación recibida en humanidades, y un 60% con la formación recibida en ciencias. Los sectores de estudios que se estima tengan una demanda más elevada de solicitudes para el curso 2013/2014 son el de la Salud y el de las Ingenierías, mientras que la estimación de los menos demandados corresponde al de Servicios de Transporte y al de Industria Manufacturera y de Producción. Se ha establecido una comparación de rankings de sectores de estudios, en la que destaca el hecho de que siendo los sectores de Matemáticas y Estadística, seguidos de Derecho y de Informática, aquellos que presentan, según datos del INE, una mayor tasa de empleo entre las personas que tienen la citada formación, están muy lejos de encontrarse entre los sectores más demandados por los estudiantes de bachillerato.Grado en Estadístic

Natalizumab-related anaphylactoid reactions in MS patients are associated with HLA class II alleles

Altres ajuts: Ajuts per donar Suport als Grups de Recerca de Catalunya," sponsored by the "Agència de Gestió d'Ajuts Universitaris i de Recerca" (AGAUR), Generalitat de CatalunyaWe aimed to investigate potential associations between human leukocyte antigen (HLA) class I and class II alleles and the development of anaphylactic/anaphylactoid reactions in patients with multiple sclerosis (MS) treated with natalizumab. HLA class I and II genotyping was performed in patients with MS who experienced anaphylactic/anaphylactoid reactions and in patients who did not develop infusion-related allergic reactions following natalizumab administration. A total of 119 patients with MS from 3 different cohorts were included in the study: 54 with natalizumab-related anaphylactic/anaphylactoid reactions and 65 without allergic reactions. HLA-DRB1*13 and HLA-DRB1*14 alleles were significantly increased in patients who developed anaphylactic/anaphylactoid reactions (p = 3 × 10 −7 ; odds ratio [OR] = 8.96, 95% confidence interval [CI] = 3.40-23.64), with a positive predictive value (PPV) of 82%. In contrast, the HLA-DRB1*15 allele was significantly more represented in patients who did not develop anaphylactic/anaphylactoid reactions to natalizumab (p = 6 × 10 −4 ; OR = 0.2, 95% CI = 0.08-0.50), with a PPV of 81%. HLA-DRB1 genotyping before natalizumab treatment may help neurologists to identify patients with MS at risk for developing serious systemic hypersensitivity reactions associated with natalizumab administration

With flowers to La Atkins

Photobook, Flowers, Gardens, Vegetables, Plants, World Photobook Day, International Photobook Day, 2021Anna Atkins nos regaló un fotolibro de algas, maravillosamente azules, que son como flores del mundo subacuático. Este año, para celebrar el Día Internacional del Fotolibro 2021, os proponemos hacer un fotolibro colectivo que será como un ramo de flores para Anna. Se trata de hacer fotos a flores, hierbas, plantas, hierbajos, suculentas, cactus... Las fotos nos van a permitir poner en el ramo lo que más nos guste sin preocuparnos de los problemas que nos daría una pieza floral fresca. Podéis sacar la foto a una flor o planta viva, vuestra o de un jardín público o del campo Podéis fotografiar algo de un herbario o una flor prensada que guardabais dentro de un libro Podéis fotografiar una foto de una flor Podéis sacarle una foto a una flor de plástico Podéis fotografiar un dibujo o una pintura (con motivos florales o vegetales, claro) Podéis fotografiar una planta carnívora (en ayunas o haciendo la digestión) Podéis fotografiar flores del mal o del "buenri" Siempre que sea vegetal y/o floral entrará en este libro ramo para Anna. ¡Queremos tanto a Anna! Vamos a mandarle flores como para una boda, como para un fiestón, como para una diva de la ópera que no conoce las alergias y le cabe de todo en el camerino, como para la primavera que está comenzando en el Cono Sur. Organizan: Biblioteca de la Facultad de Bellas Artes de la UCM Photobook Club MadridFac. de Bellas Artesunpu

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

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

Multiple sclerosis retrovirus-like envelope gene: Role of the chromosome 20 insertion

Background: The genetic basis involved in multiple sclerosis (MS) susceptibility was not completely revealed by genome-wide association studies. Part of it could lie in repetitive sequences, as those corresponding to human Endogenous Retroviruses (HERVs). Retrovirus-like particles were isolated from MS patients and the genome of the MS-associated retrovirus (MSRV) was the founder of the HERV-W family. We aimed to ascertain which chromosomal origin encodes the pathogenic ENV protein by genomic analysis of the HERV-W insertions. Methods/results: In silico analyses allowed to uncover putative open reading frames containing the specific sequence previously reported for MSRV-like envelope (env) detection. Out of the 261 genomic insertions of HERV-W env, only 9 copies harbor the specific primers and probe featuring MSRV-like env. The copy from chromosome 20 was further studied considering its size, a truncated homologue of the functional HERV-W env sequence encoding syncytin. High Resolution Melting analysis of this sequence identified two single nucleotide polymorphisms, subsequently genotyped by Taqman chemistry in 668 MS patients and 678 healthy controls. No significant association of these polymorphisms with MS risk was evidenced. Transcriptional activity of this MSRV-like env copy was detected in peripheral blood mononuclear cells from patients and controls. RNA expression levels of chromosome 20-specific MSRV-like env did not show significant differences between MS patients and controls, neither were related to genotypes of the two mentioned polymorphisms. Conclusions: The lack of association with MS risk of the identified polymorphisms together with the transcription results discard chromosome 20 as genomic origin of MSRV-like env