Neocortical tissue recovery in severe congenital obstructive hydrocephalus after intraventricular administration of bone marrow-derived mesenchymal stem cells

BACKGROUND: In obstructive congenital hydrocephalus, cerebrospinal fluid accumulation is associated with high intracranial pressure and the presence of periventricular edema, ischemia/hypoxia, damage of the white matter, and glial reactions in the neocortex. The viability and short time effects of a therapy based on bone marrow-derived mesenchymal stem cells (BM-MSC) have been evaluated in such pathological conditions in the hyh mouse model. METHODS: BM-MSC obtained from mice expressing fluorescent mRFP1 protein were injected into the lateral ventricle of hydrocephalic hyh mice at the moment they present a very severe form of the disease. The effect of transplantation in the neocortex was compared with hydrocephalic hyh mice injected with the vehicle and non-hydrocephalic littermates. Neural cell populations and the possibility of transdifferentiation were analyzed. The possibility of a tissue recovering was investigated using 1H High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance (1H HR-MAS NMR) spectroscopy, thus allowing the detection of metabolites/osmolytes related with hydrocephalus severity and outcome in the neocortex. An in vitro assay to simulate the periventricular astrocyte reaction conditions was performed using BM-MSC under high TNFα level condition. The secretome in the culture medium was analyzed in this assay. RESULTS: Four days after transplantation, BM-MSC were found undifferentiated and scattered into the astrocyte reaction present in the damaged neocortex white matter. Tissue rejection to the integrated BM-MSC was not detected 4 days after transplantation. Hyh mice transplanted with BM-MSC showed a reduction in the apoptosis in the periventricular neocortex walls, suggesting a neuroprotector effect of the BM-MSC in these conditions. A decrease in the levels of metabolites/osmolytes in the neocortex, such as taurine and neuroexcytotoxic glutamate, also indicated a tissue recovering. Under high TNFα level condition in vitro, BM-MSC showed an upregulation of cytokine and protein secretion that may explain homing, immunomodulation, and vascular permeability, and therefore the tissue recovering. CONCLUSIONS: BM-MSC treatment in severe congenital hydrocephalus is viable and leads to the recovery of the severe neurodegenerative conditions in the neocortex. NMR spectroscopy allows to follow-up the effects of stem cell therapy in hydrocephalus.España Instituto Carlos III , PI15/00619 (to AJJ), PI19/00778 (to AJJ and PPG), PI15/00796, and PI18/01557España Ministerio de Educación, Cultura y Deporte FPU13/02906España, Ministerio de Economía y Competitividad RYC-2014-16980España, FEDER Andalucía y Universidad de Málaga UMA18-FEDERJA-27

Aula itinerante de Patrimonio Cultural II

Memoria final del PIMCD UCM 2020/2021 número 31

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Risk factors of early school leaving: Andalusia middle school teachers’ perspective

High school dropout represents an important social issue, which governments and social institutions should face up. European Union countries have committed to reducing the average share of early school leavers to less than 10% by 2020 (European Union Commission, 2009).Spain has one of the highest dropouts’ rates of EU, being worse in some of Spain’s regions. This is the case of Andalusia community, which has around a 28% of early school leavers (INE, 2015) In the present work we describe some results of the research project “Students at risk for school dropout” which has been developed in Andalusia Community Spain. We used mixed methods, although in this work we only present quantitative results obtained through questionnaires, administered to 283 teachers (which is a representative sample). The value of this study lies in the fact that we have mapped the reality of secondary students in Andalusia (Spain), identifyingrisk factors. This research has also provided us with a range of aspects that could help us tackle and prevent early dropout. We analyzed risk factors identified by Middle School Teachers in several areas: academic performance, degree of commitment, attitudes and interest in school, and classroom behavior. Our main goal has been to study in depth, which are the most important risk factors, to establish new lines of action to decrease these data and prevent new cases. We conclude that the main risk factors are: difficulties in critical subjects (mathematics, language,…), dislike studying, low engagement and inappropriate classroom behavior

Prevalence and risk factors for extended-spectrum β-lactamase-producing Escherichia coli causing community-onset urinary tract infections in Colombia

Introduction Urinary tract infections (UTI) are common in the community. However, information of resistant isolates in this context is limited in Latin America. This study aims to determine the prevalence and risk factors associated with community-onset UTI (CO-UTI) caused by extended-spectrum β-lactamase (ESBL)-Producing Escherichia coli in Colombia. Materials and methods A case-control study was conducted between August and December of 2011 in three Colombian tertiary-care institutions. All patients who were admitted to the Emergency Department with a probable diagnosis of CO-UTI were invited to participate. All participating patients were asked for a urine sample. ESBL confirmatory test, antibiotic susceptibility, and molecular epidemiology were performed in these E

Evaluación de la resistencia/peso en una viga de material compuesto híbrido con fibras de algodón/vidrio

En este trabajo se presenta resultados sobre la evaluación de la resistencia/peso en una viga tipo I de material compuesto híbrido con fibras de algodón/vidrio (64% fibras de algodón y 36% fibras de vidrio). Se realizaron simulaciones numéricas a flexión a través del programa ANSYS y una prueba experimental a flexión en la máquina de ensayos Shimadzu AG-Xplus 100kN. Los resultados mostraron que es posible obtener una geometría optimizada dentro de la viga a través de la remoción estratégica de zonas de material sin comprometer la integridad estructural. Además, la prueba experimental a flexión en la viga de material compuesto mostró un valor superior en la relación de resistencia/peso (44) en comparación con la viga optimizada de aluminio 6061-T6 (39.65); este comportamiento se atribuye a que los materiales compuestos reforzados con fibras son generalmente menos densos en comparación con los metales, y a la distribución de las fibras de algodón y vidrio dentro de la viga

Neocortical tissue recovery in severe congenital obstructive hydrocephalus after intraventricular administration of bone marrow-derived mesenchymal stem cells

Background: In obstructive congenital hydrocephalus, cerebrospinal fluid accumulation is associated with high intracranial pressure and the presence of periventricular edema, ischemia/hypoxia, damage of the white matter, and glial reactions in the neocortex. The viability and short time effects of a therapy based on bone marrow-derived mesenchymal stem cells (BM-MSC) have been evaluated in such pathological conditions in the hyh mouse model. Methods: BM-MSC obtained from mice expressing fluorescent mRFP1 protein were injected into the lateral ventricle of hydrocephalic hyh mice at the moment they present a very severe form of the disease. The effect of transplantation in the neocortex was compared with hydrocephalic hyh mice injected with the vehicle and non-hydrocephalic littermates. Neural cell populations and the possibility of transdifferentiation were analyzed. The possibility of a tissue recovering was investigated using 1H High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance (1H HR-MAS NMR) spectroscopy, thus allowing the detection of metabolites/osmolytes related with hydrocephalus severity and outcome in the neocortex. An in vitro assay to simulate the periventricular astrocyte reaction conditions was performed using BM-MSC under high TNFα level condition. The secretome in the culture medium was analyzed in this assay. Results: Four days after transplantation, BM-MSC were found undifferentiated and scattered into the astrocyte reaction present in the damaged neocortex white matter. Tissue rejection to the integrated BM-MSC was not detected 4 days after transplantation. Hyh mice transplanted with BM-MSC showed a reduction in the apoptosis in the periventricular neocortex walls, suggesting a neuroprotector effect of the BM-MSC in these conditions. A decrease in the levels of metabolites/osmolytes in the neocortex, such as taurine and neuroexcytotoxic glutamate, also indicated a tissue recovering. Under high TNFα level condition in vitro, BM-MSC showed an upregulation of cytokine and protein secretion that may explain homing, immunomodulation, and vascular permeability, and therefore the tissue recovering. Conclusions: BM-MSC treatment in severe congenital hydrocephalus is viable and leads to the recovery of the severe neurodegenerative conditions in the neocortex. NMR spectroscopy allows to follow-up the effects of stem cell therapy in hydrocephalus.The present work was supported by Grants PI15/00619 (to AJJ), PI19/00778 (to AJJ and PPG), PI15/00796, and PI18/01557 (to AG) from the Instituto de Salud Carlos III, Spain, co-financed by FEDER funds from the European Union from the Instituto de Salud Carlos III, Spain, PU13/02906 to MGB from the Ministerio de Educación, Cultura y Deporte, Spain; and RYC-2014-16980 to PPG from the Ministerio de Economía y competitividad, Spain. Ayudas para publicación en abierto del plan propio (to AJJ) from Universidad de Málaga. UMA18-FEDERJA-277 (to PPG) from Plan Operativo FEDER Andalucía 2014-2020 and Universidad de Málaga. Proyectos dirigidos por jóvenes investigadores (to PPG) from Universidad de Málaga.Ye

Impact of Pneumococcal Vaccination in the Nasopharyngeal Carriage of Streptococcus pneumoniae in Healthy Children of the Murcia Region in Spain.

An epidemiological study of Streptococcus pneumoniae nasopharyngeal carriage in healthy children was carried out five years after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13). Study the impact of pediatric vaccination with PCV13, and other associated epidemiological factors on the status of nasopharyngeal carriage, the circulating pneumococcal serotypes, and the antibiotic susceptibility to more frequently used antibiotics. A multi-center study was carried out in Primary Health Care, which included 1821 healthy children aged 1 to 4 years old. All isolates were sent to the Spanish Pneumococcal Reference Laboratory for serotyping and antimicrobial susceptibility testing. At least one dose of PCV13 had been received by 71.9% of children and carriage pneumococcal prevalence was 19.7%. The proportion of PCV13 serotypes was low (14.4%), with an observed predominance of non-vaccine serotypes, 23B, 11A, 10A, 35B/F, and 23A were the five most frequent. A high rate of resistance to penicillin, erythromycin, and trimethoprim sulfamethoxazole was found. A low proportion of PCV13 serotypes were detected, confirming the impact of pediatric vaccination for reducing the serotypes vaccine carriage. High resistance rates to clinically important antibiotics were observed.This work was supported by Ministerio de Economía, Industria y Competitividad (MINECO)[grant SAF2017-83388].S

Democracia versus neoliberalismo : 25 años de neoliberalismo en Chile

El diagnóstico crítico sobre las consecuencias del sistema político económico instalado en Chile durante la dictadura militar de Pinochet parece consolidarse después de varias décadas de funcionamiento del modelo. Comienza a tomar fuerza a partir de las movilizaciones sociales ocurridas entre el 2006 y el 2011, y hoy muchos afirman la inauguración de un nuevo ciclo político, uno auspicioso para las demandas de millones de chilenos y chilenas que vieron cómo las conquistas sociales alcanzadas durante el siglo veinte por amplios sectores de la sociedad chilena, fueron abolidas y los derechos de las nuevas generaciones, conculcados. Hoy se abre la posibilidad de construir una nueva carta constitucional y de avanzar hacia una democracia efectiva que incluya a todos los sectores de la sociedad chilena. Sin embargo, el diagnóstico también es claro en afirmar que la inauguración de este ciclo no depende únicamente del sistema político que cree la nueva constitución, sino que principalmente del tránsito hacia un nuevo modelo de desarrollo. Este tránsito será demandante para todos los actores de la sociedad y especialmente para las organizaciones y los movimientos sociales, puesto que frente a la posibilidad también se abre un espacio de enorme disputa entre las clases que se han beneficiado del modelo por décadas, concentrando grandes cuotas de poder político y económico, y la gran mayoría de los chilenos y chilenas que han sufrido la desigualdad y la injusticia, asumiendo la mayor parte del riesgo por el crecimiento económico del país

Yellow fever reemergence in Venezuela – Implications for international travelers and Latin American countries during the COVID-19 pandemic

Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Grupo de Investigacíon Biomedicina. Pereira, Risaralda, Colombia / Colombian Association of Infectious Diseases. Committe on Tropical Medicine, Zoonoses and Travel Medicine. Bogota, Colombia / Fundación Universitaria Autónoma de las Américas. Grupo de Investigacíon GISCA. Semillero de Zoonosis. Sede Pereira, Pereira, Risaralda, Colombia / Instituto para la Investigación en Ciencias Biomédicas. Emerging Infectious Diseases and Tropical Medicine Research Group. Pereira, Risaralda, Colombia / Pan-American Association of Infectious Diseases. Committe on Travel Medicine. Panama City, Panama / Universidad Cientifica del Sur. Master of Clinical Epidemiology and Biostatistics. Lima, Peru / Institución Universitaria Visión de las Américas. Faculty of Medicine. Grupo de Investigacón Biomedicina. Pereira, Risaralda, Colombia / Institución Universitaria Visión de las Américas. Grupo de Investigación GISCA. Semillero de Zoonosis. Sede Pereira, Pereira, Risaralda, Colombia.Colombian Association of Infectious Diseases. Committe on Tropical Medicine, Zoonoses and Travel Medicine. Bogota, Colombia / Fundación Universitaria Autónoma de las Américas. Grupo de Investigacíon GISCA. Semillero de Zoonosis. Sede Pereira, Pereira, Risaralda, Colombia / Instituto para la Investigación en Ciencias Biomédicas. Emerging Infectious Diseases and Tropical Medicine Research Group. Pereira, Risaralda, Colombia / Institución Universitaria Visión de las Américas. Grupo de Investigación GISCA. Semillero de Zoonosis. Sede Pereira, Pereira, Risaralda, Colombia.Pan-American Association of Infectious Diseases. Committe on Travel Medicine. Panama City, Panama / Instituto Conmemorativo Gorgas de Estudios de la Salud. Clinical Research Deparment. Investigador SNI Senacyt Panama. Panama City, Panama.Pan-American Association of Infectious Diseases. Committe on Travel Medicine. Panama City, Panama / University of Colorado Anschutz Medical Center. Department of Medicine. Division of Infectious Diseases. Aurora, CO, USA / Hospital Infantil de México. Federico Góomez, Méexico City, Mexico.Biomedical Research and Therapeutic Vaccines Institute. Ciudad Bolivar, Venezuela.Colombian Association of Infectious Diseases. Committe on Tropical Medicine, Zoonoses and Travel Medicine. Bogota, Colombia / Universidad de Cordoba. Instituto de Investigaciones Biológicas del Trópico. Colombia.Colombian Association of Infectious Diseases. Committe on Tropical Medicine, Zoonoses and Travel Medicine. Bogota, Colombia / Pan-American Association of Infectious Diseases. Committe on Travel Medicine. Panama City, Panama / Hospital Universitario de Sincelejo. Infectious Diseases and Infection Control Research Group. Sincelejo, Sucre, Colombia / Universidad del Atlático. SUE Caribe. Programa del Doctorado de Medicina Tropical. Barranquilla, Colombia.Colombian Association of Infectious Diseases. Committe on Tropical Medicine, Zoonoses and Travel Medicine. Bogota, Colombia / Universidad Cooperativa de Colombia. Grupo de Investigación en Ciencias Animales. Bucaramanga, Colombia.Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Grupo de Investigacíon Biomedicina. Pereira, Risaralda, Colombia / Colombian Association of Infectious Diseases. Committe on Tropical Medicine, Zoonoses and Travel Medicine. Bogota, Colombia / Instituto para la Investigación en Ciencias Biomédicas. Emerging Infectious Diseases and Tropical Medicine Research Group. Pereira, Risaralda, Colombia / Pan-American Association of Infectious Diseases. Committe on Travel Medicine. Panama City, Panama / Fundación Universitaria Autónoma de las Américas. Faculty of Medicine. Semillero de Investigación en Infecciones Emergentes y Medicina Tropical. Pereira, Risaralda, Colombia / Institución Universitaria Visión de las Américas. Faculty of Medicine. Grupo de Investigacón Biomedicina. Pereira, Risaralda, Colombia.Instituto Médico La Floresta. Caracas, Venezuela.Universidad del Norte and Hospital Universidad del Norte. Department of Medicine, Health Sciences Division. Barranquilla, Colombia.Pan-American Association of Infectious Diseases. Committe on Travel Medicine. Panama City, Panama / Universidad Central de Venezuela. Faculty of Medicine. Caracas, Venezuela.Institute of Infectious Diseases Emilio Ribas, São Paulo, SP, Brazil.Universidad Estatal del Sur de Manabí. Carrera de Laboratorio Clínico. Cantón Jipijapa, Ecuador.Universidad Católica del Maule. Vicerrectoría de Investigación y Postgrado. Chile.Universidad Central de Venezuela. Faculty of Medicine. Hospital Universitario de Caracas. Department of Internal Medicine. Cardiology Division. Caracas, Venezuela.Hospital José María Vargas. La Guaira, Vargas, Venezuela.Universidad Castilla La Mancha. Facultad de Medicina. Complejo Hospitalario Universitario de Albacete. Servicio de Anatomía Patológica. Albacete, Spain.International Airport Camilo Daza. Health Care Service. Cúcuta, Norte de Santander, Colombia.Universidade de São Paulo. Faculdade de Saúde Pública. Departamento de Epidemiologia. São Paulo, SP, Brazil.Universidad Técnica de Ambato. Ambato, Ecuador.Hospital Transfrontalier Cerdayna. Catalonia, Spain.University of Illinois. Department of Internal Medicine. Division of Infectious Diseases. Chicago, IL, USA.Hospital Evangélico de Montevideo. Montevideo, Uruguay.Universidad Cooperativa de Colombia. Grupo de Investigación en Ciencias Animales. Bucaramanga, Colombia.Instituto Nacional de Salud del Niño San Borja. Infectious Diseases Division. Lima, Peru / Universidad Privada de Tacna. Facultad de Ciencias de la Salud. Tacna, Peru.Hospital Universitario Departamental de Nariño. Pasto, Nariño, Colombia.Universidad de Manizales. School of Medicine. Coordination of Microbiology. Manizales, Caldas, Colombia / Grupo de Resistencia Antibiótica de Manizales. Manizales, Caldas, Colombia.Clínica San Josée. Cúcuta, Norte de Santander, Colombia / Hospital Universitario Erasmo Meoz. Cúcuta, Norte de Santander, Colombia.Hospital de Niños J. M. de Los Ríos. Division of Infectious Diseases. Caracas, Venezuela / Venezuelan Society of Infectious Diseases. Executive Board. Caracas, Venezuela.University of Colorado Anschutz Medical Center. Department of Medicine. Division of Infectious Diseases. Aurora, CO, USA.Universidad Industrial de Santander. Department of Internal Medicine. Bucaramanga, Santander, Colombia.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil / aq Universidade Federal do Para. Faculdade de Medicina. Belém, PA, Brasil.Hospital de Infecciosas F. Muñíz. Buenos Aires, Argentina.GSK Vaccines. Clinical Research & Development and Medical Affairs. Rio de Janeiro, RJ, Brazil.Hospital de Trauma y Emergencias Federico Abete. Buenos Aires, Argentina.Hospital Británico de Buenos Aires. Buenos Aires, Argentina.Pontificia Universidad Católica de Chile. School of Medicine. Department of Pediatric Infectious Diseases and Immunology. Santiago de Chile, Chile.Hospital de Infecciosas F. Muñíz. Buenos Aires, Argentina.Hospital de Infecciosas F. Muñíz. Buenos Aires, Argentina / Universidad de Buenos Aires. Buenos Aires, Argentina.Latin American Society for Travel Medicine. Panel of Sports and Travel. Buenos Aires, Argentina.Universidad Internacional SEK. Health Sciences Faculty. Research Group of Emerging Diseases, Ecoepidemiology and Biodiversity. Quito, Ecuador / Universidad Central de Venezuela. Facultad de Ciencias. Instituto de Zoología y Ecología Tropical. Caracas, Venezuela.Pan-American Association of Infectious Diseases. Committe on Travel Medicine. Panama City, Panama / Instituto de Investigaciones Biomédicas. Clínica IDB Cabudare. Department of Infectious Diseases and Tropical Medicine. Lara, Venezuela / Venezuelan Science Incubator and the Zoonosis and Emerging Pathogens Regional Collaborative Network. Infectious Diseases Research Branch. Lara, Venezuela / Instituto de Estudios Avanzados. Laboratorio de Señalización Celular y Bioquímica de Parásitos. Caracas, Caracas, Venezuela / Academia Nacional de Medicina. Caracas, Venezuela / The Mount Sinai Hospital-Icahn School of Medicine at Mount Sinai. Department of Pathology, Molecular and Cellbased Medicine. Direction of Microbiology. New York, USA