TREM2 expression in the brain and biological fluids in prion diseases

Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune cell surface receptor that regulates microglial function and is involved in the pathophysiology of several neurodegenerative diseases. Its soluble form (sTREM2) results from shedding of the TREM2 ectodomain. The role of TREM2 in prion diseases, a group of rapidly progressive dementias remains to be elucidated. In the present study, we analysed the expression of TREM2 and its main sheddase ADAM10 in the brain of sporadic Creutzfeldt-Jakob disease (sCJD) patients and evaluated the role of CSF and plasma sTREM2 as a potential diagnostic marker of prion disease. Our data indicate that, compared to controls, TREM2 is increased in sCJD patient brains at the mRNA and protein levels in a regional and subtype dependent fashion, and expressed in a subpopulation of microglia. In contrast, ADAM10 is increased at the protein, but not the mRNA level, with a restricted neuronal expression. Elevated CSF sTREM2 is found in sCJD, genetic CJD with mutations E200K and V210I in the prion protein gene (PRNP), and iatrogenic CJD, as compared to healthy controls (HC) (AUC = 0.78-0.90) and neurological controls (AUC = 0.73-0.85), while CSF sTREM2 is unchanged in fatal familial insomnia. sTREM2 in the CSF of cases with Alzheimer's disease, and multiple sclerosis was not significantly altered in our series. CSF sTREM2 concentrations in sCJD are PRNP codon 129 and subtype-related, correlate with CSF 14-3-3 positivity, total-tau and YKL-40, and increase with disease progression. In plasma, sTREM2 is increased in sCJD compared with HC (AUC = 0.80), displaying positive correlations with plasma total-tau, neurofilament light, and YKL-40. We conclude that comparative study of TREM2 in brain and biological fluids of prion diseases reveals TREM2 to be altered in human prion diseases with a potential value in target engagement, patient stratification, and disease monitoring

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

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

CIBERER: Spanish national network for research on rare diseases: A highly productive collaborative initiative

13 páginas,1 figura, 3 tablas, 1 apéndice. Se extraen los autores pertenecientes a The CIBERER network que trabajan en Centros del CSIC del Appendix ACIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research.This study has been funded by Instituto de Salud Carlos III (ISCIII) and Spanish Ministry of Science and InnovationPeer reviewe

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Post-Franco Theatre

In the multiple realms and layers that comprise the contemporary Spanish theatrical landscape, “crisis” would seem to be the word that most often lingers in the air, as though it were a common mantra, ready to roll off the tongue of so many theatre professionals with such enormous ease, and even enthusiasm, that one is prompted to wonder whether it might indeed be a miracle that the contemporary technological revolution – coupled with perpetual quandaries concerning public and private funding for the arts – had not by now brought an end to the evolution of the oldest of live arts, or, at the very least, an end to drama as we know it

I Congresso Ibero-Americano de Bibliotecas Escolares

Actas de la primera edición del I Congreso Iberoamericano de Bibliotecas Escolares, CIBES 2015, organizado por la Universidad Carlos III de Madrid (España), la Universidad Estatal Paulista (Brasil) y el Ayuntamiento de Getafe (España). Celebrado: 21 - 23 de octubre de 2015 en la Universidad Estatal Paulista (Marília) y 26 - 28 de octubre de 2015 en la Universidad Carlos III de Madrid (Getafe)Universidad Carlos III de Madrid (España)Universidad Estatal Paulista (Brasil)Ayuntamiento de Getafe (España)Dimensiones y visiones de la biblioteca escolar en una Educación por competencias: la necesidad de una política estratégica / Miguel Ángel Marzal. -- Getafe ciudad educadora, lectora y escritora: Bibliotecas escolares / Lourdes Muñoz Santiuste. -- Presente y futuro: biblioteca escolar-CREA y proyectos interdisciplinares / Rosa Piquín. -- Cultura en información: un reto esencial de la biblioteca escolar / Mónica Baró. -- Bibliotecas escolares de Galicia: un mundo de oportunidades a favor de la Educación / Cristina Novoa. -- 10 años de la Red de Bibliotecas Escolares de Extremadura (REBEX) / Casildo Macías Pereira. -- Biblioteca Escolar y uso ético de la información para una Cultura de Paz / Ana Barrero Tíscar. -- Dinamización de la Biblioteca Escolar Plumita durante el curso escolar 2014/15 / María Antonia Cano Cañada. -- Experiencia de la creación de una biblioteca escolar / Susana Santos Martín. -- Grupo cooperativo Bibliotecas escolares en Red-Albacete / José Manuel Garrido Argandoña y Eva Leal Scasso. -- La BCREA "Juan Leiva". El fomento de la lectura desde la web social / Andrés Pulido Villar. -- Proceso de implantación de una herramienta de autoevaluación en la red de bibliotecas escolares de Extremadura (REBEX) / Casildo Macías Pereira. -- La biblioteca escolar: abriendo fronteras / Lorena Verónica Cabrera Orellana. -- O programa RBE e a avaliaçao das bibliotecas escolares: melhoria, desenvolvimiento e innovaçao / Elsa Conde. -- Profesional de Biblioteconomía y Documentación: esencial en la plantilla de la escuela / Pilar del Campo Puerta. -- Una mirada activa al proceso educativo desde la biblioteca escolar / María Jesús Fontela Fernández . -- Con otra mirada "La ilustración como vehículo de comunicación y aprendizaje en las bibliotecas escolares" / Pablo Jurado Sánchez-Galán. -- Fingertips. Recriar a biblioteca escolar na sala de aula / Rui Alfonso Mateus. -- Hablemos de libros. Cómo transformar una clase de literatura en una comunidad de interpretación de textos / Francisco César Díaz Rey. -- Inclusión social de familias inmigrantes a través de un programa de aprendizaje de la lengua castellana / Ana Carmen Tolino Fernández-Henarejos. -- O desenvolvimento de atividades de mediação de leitura em biblioteca escolar: o caso da biblioteca da Escola Sesc de Ensino Médio / Vagner Amaro. -- La biblioteca escolar. Proceso de enseñanza-aprendizaje de padres a hijos / Ana Carmen Tolino Fernández- Henarejos. -- Leo con y para los demás / Ismael Fernández Fernández, Ana María Moreno Vicente y Ana Beatriz Vicente Pérez. -- Nanas y arrullo. Poesía a la deriva / Bernardo Fuentes Navarrete y Carlos García-Romeral Pérez. -- Gestión y evaluación de servicios bibliotecarios para personas con dislexia: una biblioteca escolar inclusiva desde una perspectiva internacional / Carmen Jorge García-Reyes. -- Sueños lectores compartidos hechos realidad: la biblioteca escolar del C.E.I.P-S.E.S-A.A “LA PAZ” de Albacete / Ana Rosa Cabañero Tobarra, Juan Manuel Herráez, Eva Leal Scasso, María Marín Sánchez, Ana Belén Medrano Martínez y María José Nortes Ruipérez. -- El programa biblioteca escuela en Civican. La literatura como elemento motivador para la alfabetización informacional / Villar Arellano Yanguas. -- La competencia digital en el diseño curricular: desde la biblioteca al aula / Felicidad Campal García. -- O deselvomimento da pesquisa escolar por meio da competência em informaçao / Luciane de Fátima Cavalcante Beckman y Marta Leandro da Mata. -- Proyecto escolar de investigación documental "Te pillé leyendo" / José Manuel Garrido Argandoña. -- Aprender com a Biblioteca Escolar: formar para as literacias / Paula Correia y Isabel Mendinhos. -- Sucedió en el siglo XX / María Antonia Becerra Montalbán, Ángel Bernabé Muñoz y Sofía Vaz Romero. -- El Club de lectura en la nube / Belén Benito Blázquez y Ana Ordás García. -- Promover a leitura e a escrita na era digital: prácticas nas bibliotecas escolares / María Raquel Ramos. -- A biblioteca escolar e o desafío da interculturalidade: o projeto Ser + cidadao / María da Conceição Tomé. -- Cuando la competencia digital encontró a la alfabetización informacional o Mucho ruido y pocas nueces / Felicidad Campal García. -- Hora de ler, un programa para el fomento de la lectura en contexto educativo / Cristina Novoa. -- Hábitos de lectura para las competencias en información y alfabetización en información en bibliotecas escolares de Puerto Rico / Karen Denise Centeno Casillas. -- Repositorios digitales en las bibliotecas escolares andaluzas: situación, modelos y herramientas para su creación / Dolores Olmos Olmos y Andrés Pulido Villar. -- Trabajando las competencias clave con las aventuras de Mozarito en Extremadura / María Teresa Carballosa González y María Esther Nieto Vidal. -- Análisis de modelos de evaluación de la web de la biblioteca escolar / Raúl Cremades García. -- Emociónate con las historias: El bosque de las emociones e historias con mucho teatro / Esther Luis Pérez y Ana María Peromingo Fernández. -- Biblioteca escolar de innovación y continuación / E. María Guerrero Palacios y Silvia Mora Ramírez. -- Uso de estándares y licencias para la creación y difusión de contenidos en las bibliotecas escolares / José Luis Barreiro Cebey. -- La biblioteca escolar digital móvil / Javier Fernández Delgado. -- Uso de aplicaciones móviles para el desarrollo de la competencia lingüística. Proyecto Hansel App Gretel / Dolores Olmos Olmos. -- A memória e a mediação segundo Vigotski / Leda Maria Araújo, Patricia Celia Santana, Sueli Bortolin y Leticia Gorri Molina. -- Bibliotecas escolares como tema de estudo dos alunos de graduação em blioteconomia do Instituto de Ensino Superior da FUNLEC: estado da arte / Tiago Pereira Nocera y Rodrigo Pereira. -- Ações de mediação da leitura e da informação em bibliotecas escolares: um olhar sobre as bibliotecas dos Colégios de Aplicação / Tatyanne Christina Gonçalves Ferreira Valdez y Alberto Calil Júnior. -- Mediação pedagógica numa biblioteca de escola pública em Londrina / Rovilson José da Silva, Teba Silva Yllana y Sueli Bortolin. -- Utilização de categorias por cores em sistema de biblioteca voltado ao público infanto-juvenil / Liliana Giusti Serra. -- Atividades de ensino dos atos de leitura com crianças em risco social / Adriana Naomi Fukushima da Silva y Dagoberto Buim Arena. -- Biblioteca escolar: espaço de significados entre alunos, professores e bibliotecários / Rodrigo Barbosa Paulo, Marisa Xavier, Helen Castro Casarin y Creuza Barbaroto. -- A Biblioteca Escolar no Contexto da Legislação e do Processo Educativo / Eliane Lourdes da Silva Moro, Francisca Rosaline Leite Mota y Raimundo Martins de Lima. -- O jornal impresso como fonte de informação: a importância da formação de leitores críticos / Mariana Pícaro Cerigatto. -- Bibliotecas escolares no estado do Rio Grande do Sul: a trajetória de realização dos fóruns gaúchos pela melhoria das bibliotecas escolares / Eliane Lourdes da Silva Moro y Lizandra Brasil Estabel. -- O acesso à informação dos usuários surdos na biblioteca escolar / André Luís Onório Coneglian y Mayara Melo Santana. -- Aprendizagem coletiva de bibliotecários e a competência de pesquisa dos docentes: o caso do Instituto Federal do Espírito Santo / Maristela Almeida Mercandeli Rodrigues y Beatriz Quiroz Villardi. -- Biblioteca escolar: atores, parâmetros e competências / Mavi Galante Mancera Dall´Acqua Carvalho y Claudio Marcondes de Castro Filho. -- Estratégias de aprendizagem de escrita no Ensino Fundamental II / Érika Christina Kohle. -- Bebês e livros: leitura nas bebetecas. Kenia Adriana de Aquino Modesto Silva, Juliane Francischeti Martins Motoyama y Renata Junqueira de Souza. -- Práticas alternativas para organização de acervos nos espaços de leitura em ambientes escolares / Luciana Souza Gracioso, Ariovaldo Alves, Débora Nascimento, Suelen Redondo, Tainara Torika Kiri de Castro, Elizabete Angelon y Eduardo Barbosa. -- Reflexões sobre a modelagem e criação de uma Rede Virtual de Leitores para Bibliotecas Escolares / Carla Floriana Martins y Raoni Guerra Rajão. -- Biblioteca escolar: espaço de formação leitora? / Silvana Ferreira de Souza Balsan y Renata Junqueira de Souza. -- “Se a Biblioteca Escolar é minha mãe, o Google é meu pai”: representações da relação entre Biblioteca Escolar e Google no imaginário de alunos do ensino técnico / Adriana Bogliolo Sirihal-Duarte, Maria L. Amorim Antunes y Raquel Miranda Vilela Paiva. -- Desafios e propostas para a universalização das bibliotecas escolares no Brasil e na Espanha / Rodrigo Pereira, Daniela Spudeit y Fernanda de Sales. -- Bibliotecário educador: possibilidades de atuação no contexto da biblioteca escolar / André Carlos da Silva, Valéria Martin Valls y Mariana de Paula Silva. -- Uma ONG para Bibliotecas Escolares : estratégia para ampliar a igualdade e capacidade de acesso e uso da informação e educação escolar de qualidade / Suelen Camilo Ferreira y Luciana de Souza Gracioso. -- O aluno com deficência: o papel do bibliotecário na disponibilidade de recursos acessíveis na biblioteca escolar / Adriano de Sales Coelho, Rosilene de Melo Oliveira y Marcos Pastana Santos. -- Biblioteca digital virtual e o uso do tablete: uma possibilidade de construção de novas práticas de leitura na escola / Barbara Cibelli da Silva Monteagudo y Dagoberto Buim Arena. -- A importância da biblioteca na educação de crianças de 0 a 3 anos / Yngrid Karolline Mendonça Costa y Cyntia Graziella Guizelim Simões Girotto. -- Comportamento Informacional de adolescentes: a relação com bibliotecas e escolas / Nelson Sebastian Silva-Jerez y Helen de Castro S. Casarin

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM