Novel antiprotozoal products: Imidazole and benzimidazole N-oxide derivatives and related compounds

The syntheses and biological evaluation of the first anti-protozoa imidazole N-oxide and benzimidazole N-oxide and their derivatives are reported. They were tested in vitro against two different protozoa, Trypanosoma cruzi and Trichomonas vaginalis. Derivative 7c, ethyl-1-(i-butyloxycarbonyloxy)-6-nitrobenzimid-azole-2-carboxylate, displayed activity on both protozoa. Lipophilicity and redox potential were experimentally determined in order to study the relationship with activity of the compounds. These properties are well related with the observed bioactivity. Imidazole and benzimidazole N-oxide derivatives are becoming leaders for further chemical modifications and advanced biological studies

Towards a Combined Use of Geophysics and Remote Sensing Techniques for the Characterization of a Singular Building: “El Torreón” (the Tower) at Ulaca Oppidum (Solosancho, Ávila, Spain)

This research focuses on the study of the ruins of a large building known as “El Torreón” (the Tower), belonging to the Ulaca oppidum (Solosancho, Province of Ávila, Spain). Different remote sensing and geophysical approaches have been used to fulfil this objective, providing a better understanding of the building’s functionality in this town, which belongs to the Late Iron Age (ca. 300–50 BCE). In this sense, the outer limits of the ruins have been identified using photogrammetry and convergent drone flights. An additional drone flight was conducted in the surrounding area to find additional data that could be used for more global interpretations. Magnetometry was used to analyze the underground bedrock structure and ground penetrating radar (GPR) was employed to evaluate the internal layout of the ruins. The combination of these digital methodologies (surface and underground) has provided a new perspective for the improved interpretation of “El Torreón” and its characteristics. Research of this type presents additional guidelines for better understanding of the role of this structure with regards to other buildings in the Ulaca oppidum. The results of these studies will additionally allow archaeologists to better plan future interventions while presenting new data that can be used for the interpretation of this archaeological complex on a larger scale

Natural estrogens enhance the engraftment of human hematopoietic stem and progenitor cells in immunodeficient mice

Hematopoietic Stem and Progenitor Cells are crucial in the maintenance of lifelong production of all blood cells. These Stem Cells are highly regulated to maintain homeostasis through a delicate balance between quiescence, self-renewal and differentiation. However, this balance is altered during the hematopoietic recovery after Hematopoietic Stem and Progenitor Cell Transplantation. Transplantation efficacy can be limited by inadequate Hematopoietic Stem Cells number, poor homing, low level of engraftment, or limited self-renewal. As recent evidences indicate that estrogens are involved in regulating the hematopoiesis, we sought to examine whether natural estrogens (estrone or E1, estradiol or E2, estriol or E3 and estetrol or E4) modulate human Hematopoietic Stem and Progenitor Cells. Our results show that human Hematopoietic Stem and Progenitor Cell subsets express estrogen receptors, and whose signaling is activated by E2 and E4 on these cells. Additionally, these natural estrogens cause different effects on human Progenitors in vitro. We found that both E2 and E4 expand human Hematopoietic Stem and Progenitor Cells. However, E4 was the best tolerated estrogen and promoted cell cycle of human Hematopoietic Progenitors. Furthermore, we identified that E2 and, more significantly, E4 doubled human hematopoietic engraftment in immunodeficient mice without altering other Hematopoietic Stem and Progenitor Cells properties. Finally, the impact of E4 on promoting human hematopoietic engraftment in immunodeficient mice might be mediated through the regulation of mesenchymal stromal cells in the bone marrow niche. Together, our data demonstrate that E4 is well tolerated and enhances human reconstitution in immunodeficient mice, directly by modulating human Hematopoietic Progenitor properties and indirectly by interacting with the bone marrow niche. This application might have particular relevance to ameliorate the hematopoietic recovery 3 after myeloablative conditioning, especially when limiting numbers of Hematopoietic Stem and Progenitor Cells are available

Identification of the Immunological Changes Appearing in the CSF During the Early Immunosenescence Process Occurring in Multiple Sclerosis

Patients with multiple sclerosis (MS) suffer with age an early immunosenescence process, which influence the treatment response and increase the risk of infections. We explored whether lipid-specific oligoclonal IgM bands (LS-OCMB) associated with highly inflammatory MS modify the immunological profile induced by age in MS. This cross-sectional study included 263 MS patients who were classified according to the presence (M+, n=72) and absence (M-, n=191) of LS-OCMB. CSF cellular subsets and molecules implicated in immunosenescence were explored. In M- patients, aging induced remarkable decreases in absolute CSF counts of CD4+ and CD8+ T lymphocytes, including Th1 and Th17 cells, and of B cells, including those secreting TNF-alpha. It also increased serum anti-CMV IgG antibody titers (indicative of immunosenescence) and CSF CHI3L1 levels (related to astrocyte activation). In contrast, M+ patients showed an age-associated increase of TIM-3 (a biomarker of T cell exhaustion) and increased values of CHI3L1, independently of age. Finally, in both groups, age induced an increase in CSF levels of PD-L1 (an inductor of T cell tolerance) and activin A (part of the senescence-associated secretome and related to inflammaging). These changes were independent of the disease duration. Finally, this resulted in augmented disability. In summary, all MS patients experience with age a modest induction of T-cell tolerance and an activation of the innate immunity, resulting in increased disability. Additionally, M- patients show clear decreases in CSF lymphocyte numbers, which could increase the risk of infections. Thus, age and immunological status are important for tailoring effective therapies in MS.This work was supported by grants FIS-PI15/00513, FIS-PI18/00572 and RD16/0015/0001 from the Instituto de Salud Carlos III. Ministerio de Ciencia e Innovación, Spain and FEDER: "Una manera de hacer Europa"

Risk and outcomes of COVID-19 in patients with multiple sclerosis

Background and purpose Limited information is available on incidence and outcomes of COVID-19 in patients with multiple sclerosis (MS). This study investigated the risks of SARS-CoV-2 infection and COVID-19-related outcomes in patients with MS, and compared these with the general population. Methods A regional registry was created to collect data on incidence, hospitalization rates, intensive care unit admission, and death in patients with MS and COVID-19. National government outcomes and seroprevalence data were used for comparison. The study was conducted at 14 specialist MS treatment centers in Madrid, Spain, between February and May 2020. Results Two-hundred nineteen patients were included in the registry, 51 of whom were hospitalized with COVID-19. The mean age ± standard deviation was 45.3 ± 12.4 years, and the mean duration of MS was 11.9 ± 8.9 years. The infection incidence rate was lower in patients with MS than the general population (adjusted incidence rate ratio = 0.78, 95% confidence interval [CI] = 0.70–0.80), but hospitalization rates were higher (relative risk = 5.03, 95% CI = 3.76–6.62). Disease severity was generally low, with only one admission to an intensive care unit and five deaths. Males with MS had higher incidence rates and risk of hospitalization than females. No association was found between the use of any disease-modifying treatment and hospitalization risk. Conclusions Patients with MS do not appear to have greater risks of SARS-CoV-2 infection or severe COVID-19 outcomes compared with the general population. The decision to start or continue disease-modifying treatment should be based on a careful risk–benefit assessment.post-print996 K

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

El impacto del aprendizaje universitario colaborativo el rendimiento académico del estudiante: Una wiki para la ciencia política y de la administración

El objetivo del proyecto es llevar a la práctica una acción formativa basada en la web 2.0 con la participación de profesores y alumnos pertenecientes a distintos grados, facultades y universidades. En concreto, esta iniciativa pretende continuar con la wiki, www.dcpa.wikidot.com, que comenzó a realizarse en 2015 en virtud de la convocatoria de PIMCD. La wiki contribuye a que los estudiantes, de manera colaborativa, diseñen un proyecto educativo de integración curricular a partir de unos supuestos establecidos previamente por el profesor. Por lo tanto, este tipo de experiencia permite crear una base documental de gran utilidad para otros alumnos que estudian este tipo de asignaturas o para cualquier persona que muestren una inquietud o necesidad de buscar, encontrar o ampliar el conocimiento sobre determinadas cuestiones relacionadas con la ciencia política y la ciencia de la administració

Pereda. Corrales. Com

Se trata de la publicación de una revista digital en la página web del centro, en la que colaboran para su elaboración, padres/madres, alumnos/as y profesores/as. Los objetivos del mismo: educar a los alumnos para la sociedad e la información, usar la red para formar alumnos, profesores, padres en el proceso de la comunicación, aportar un espacio global y facilmente accesible a la información de la comunidad, posibilitar un espacio compartido de información entre alumnos, padres y profesores. El sistema de trabajo llevado a cabo: publicar en la página web del centro, los alumnos aprender a navegar, confección de un correo electrónico gratuito, establecer un correo electrónico con otros centros. La evaluación del proyecto ha sido muy positiva para todos los sectores implicados en el mismo, tanto alumnos, como padres y profesores.Gobierno de Cantabria. Consejería de Educación y JuventudCantabriaES

Algo más que un patio : un proyecto de Educación Ambiental en Zaleo

Trata la adecuación del patio escolar como recurso para una mejor intervención educativa y como lugar de exploración y observación. Pretende fomentar las relaciones entre los miembros de la comunidad escolar; facilitar espacios y materiales que favorezcan el desarrollo del alumnado con necesidades educativas especiales; ofrecer al alumnado posibilidades de desarrollo de las distintas capacidades (movimiento, exploración, relación con el medio natural, interacciones con niños-as de otras edades); crear normas adecuadas para el uso y mantenimiento de los espacios y materiales del patio, fomentando el respeto por ellos y valorar la importancia del cuidado del medio ambiente, desde actitudes y valores de respeto de su patio como entorno más cercano. Las actividades se desarrollan en torno al reciclado de materiales, juegos de la naturaleza, construcción de juguetes, juegos al aire libre y disfraces. A partir de la observación se evalúa el grado de participación y cambio de actitudes.Madrid (Comunidad Autónoma). Consejería de Educación y CulturaMadridMadrid (Comunidad Autónoma). Subdirección General de Formación del Profesorado. CRIF Las Acacias; General Ricardos 179 - 28025 Madrid; Tel. + 34915250893ES