Characterization of an enhanced antigenic change in the pandemic 2009 H1N1 influenza virus haemagglutinin

Murine hybridomas producing neutralizing mAbs specific to the pandemic influenza virus A/California/07/2009 haemagglutinin (HA) were isolated. These antibodies recognized at least two different but overlapping new epitopes that were conserved in the HA of most Spanish pandemic isolates. However, one of these isolates (A/Extremadura/RR6530/2010) lacked reactivity with the mAbs and carried two unique mutations in the HA head (S88Y and K136N) that were required simultaneously to eliminate reactivity with the murine antibodies. This unusual requirement directly illustrates the phenomenon of enhanced antigenic change proposed previously for the accumulation of simultaneous amino acid substitutions at antigenic sites of the influenza A virus HA during virus evolution (Shih et al., Proc Natl Acad Sci USA, 104 , 6283-6288, 2007). The changes found in the A/Extremadura/RR6530/2010 HA were not found in escape mutants selected in vitro with one of the mAbs, which contained instead nearby single amino acid changes in the HA head. Thus, either single or double point mutations may similarly alter epitopes of the new antigenic site identified in this work in the 2009 H1N1 pandemic virus HA. Moreover, this site is relevant for the human antibody response, as shown by competition of mAbs and human post-infection sera for virus binding. The results are discussed in the context of the HA antigenic structure and challenges posed for identification of sequence changes with possible antigenic impact during virus surveillance.This work was supported in part by grants GR09/0023 (A. N.), GR09/0039 (J. A. M.) and GR09/0040 (I. C.) from Instituto de Salud Carlos III under a special research programme on pandemic flu. Additionally, the Biología Viral Unit is supported currently by grant SAF2012-31217 from Plan Nacional I+D+i.S

A neutralizing single-domain antibody that targets the trimer interface of the human metapneumovirus fusion protein

Human metapneumovirus (hMPV) is an important respiratory pathogen for which no licensed antivirals or vaccines exist. Single-domain antibodies represent promising antiviral biologics that can be easily produced and formatted. We describe the isolation and detailed characterization of two hMPV-neutralizing single-domain antibodies that are directed against the fusion protein F. One of these single-domain antibodies broadly neutralizes hMPV A and B strains, can prevent proteolytic maturation of F, and binds to an epitope in the F trimer interface. This suggests that hMPV pre-F undergoes trimer opening or "breathing" on infectious virions, exposing a vulnerable site for neutralizing antibodies. Finally, we show that this single-domain antibody, fused to a human IgG1 Fc, can protect cotton rats against hMPV replication, an important finding for potential future clinical applications.This work was supported by a grant from Janssen Pharmaceuticals Inc. to X.S. and Welch Foundation grant number F-0003-19620604 to J.S.M.S

Potently neutralizing and protective anti-human metapneumovirus antibodies target diverse sites on the fusion glycoprotein

Human metapneumovirus (hMPV) is a leading cause of acute lower respiratory tract infections in high-risk populations, yet there are no vaccines or anti-viral therapies approved for the prevention or treatment of hMPV-associated disease. Here, we used a high-throughput single-cell technology to interrogate memory B cell responses to the hMPV fusion (F) glycoprotein in young adult and elderly donors. Across all donors, the neutralizing antibody response was primarily directed to epitopes expressed on both pre- and post-fusion F conformations. However, we identified rare, highly potent broadly neutralizing antibodies that recognize pre-fusion-specific epitopes and structurally characterized an antibody that targets a site of vulnerability at the pre-fusion F trimer apex. Additionally, monotherapy with neutralizing antibodies targeting three distinct antigenic sites provided robust protection against lower respiratory tract infection in a small animal model. This study provides promising monoclonal antibody candidates for passive immunoprophylaxis and informs the rational design of hMPV vaccine immunogens.We acknowledge the Immune Monitoring and Flow Cytometry Resource (IMFCSR) at the Norris Cotton Cancer Center at Dartmouth supported by NCI Cancer Center Support Grant 5P30CA023108-41. This work was funded in part by Welch Foundation grant number F-0003-19620604.S

Prevalence of Symptomatic Osteoarthritis in Spain: EPISER2016 Study

[Resumen] Introducción. La Sociedad Española de Reumatología elaboró en el año 2000 el estudio EPISER2000 para conocer la prevalencia de la artrosis y otras enfermedades reumáticas en España. Los cambios sociodemográficos y en los hábitos de vida ocurridos en los últimos años en España justifican actualizar los datos de las enfermedades reumáticas (EPISER2016). Objetivo. Estimar la prevalencia de artrosis sintomática de columna cervical, columna lumbar, cadera, rodilla y mano, en población adulta en España. Material y métodos. Estudio transversal de base poblacional. Se realizó un muestreo aleatorizado polietápico estratificado y por conglomerados. Los participantes fueron contactados por teléfono para cumplimentar un cuestionario de cribado de artrosis. El reumatólogo confirmaba o descartaba el diagnóstico. Se utilizaron los criterios-clínicos-ACR para diagnosticar artrosis de manos y los criterios clínico-radiológicos-ACR para diagnosticar la artrosis de rodilla y cadera. Resultados. La prevalencia de artrosis en España en una o más de las localizaciones estudiadas fue de 29,35%. La prevalencia de artrosis-cervical fue del 10,10% y de artrosis-lumbar del 15,52%. Ambas son más frecuentes en mujeres y a mayor edad, así como en personas con niveles de estudios bajos y obesidad. La prevalencia de artrosis de cadera fue del 5,13% y la de artrosis de rodilla del 13,83%; estas se asocian con el sexo femenino, sobrepeso y obesidad, menor frecuencia en nivel de estudios alto y con la edad. La prevalencia de la artrosis de mano fue del 7,73%. Es más frecuente en mujeres, obesas, con bajo nivel de estudios y mayor edad. Conclusiones. El estudio EPISER2016 es el primero que analiza la prevalencia de artrosis sintomática en 5 localizaciones (columna cervical, lumbar, rodilla, cadera y manos) en España. La artrosis de la columna lumbar es la más prevalente.[Abstract] Introduction. The Spanish Society of Rheumatology carried out the EPISER2000 study in 2000 to determine the prevalence of osteoarthritis and other rheumatic diseases in the Spanish population. Recent sociodemographic changes and lifestyle habits in Spain justified updating the epidemiological data on osteoarthritis and other rheumatic diseases (EPISER2016-study). Objective. To estimate the prevalence of symptomatic osteoarthritis of the cervical spine, lumbar spine, hip, knee and hand in the adult population in Spain. Material and methods. Cross-sectional population-based study. A multistage and stratified random cluster sampling was carried out. The participants were contacted by telephone to complete an osteoarthritis screening questionnaire. A rheumatologist confirmed or discarded the diagnosis. The ACR-clinical-criteria were used to diagnose hand-osteoarthritis and the ACR-clinical-radiological criteria to diagnose knee- and hip-osteoarthritis. To estimate the prevalence and its 95% confidence interval, weights were calculated according to the probability of selection in each of the sampling stages. Results. The prevalence of osteoarthritis in Spain in one or more of the locations studied was 29.35%. The prevalence of cervical-osteoarthritis was 10.10% and of lumbar-osteoarthritis 15.52%. Both are more frequent in women and at older ages, as well as in people with low levels of education and obesity. The prevalence of hip-osteoarthritis was 5.13%, that of knee-osteoarthritis 13.83%, these are associated with female sex, overweight and obesity. The prevalence of hand osteoarthritis was 7.73%. It is more frequent in women, who are obese, with a low educational level and who are older. Conclusion. The EPISER2016 study is the first to analyse the prevalence of symptomatic osteoarthritis in 5 locations (cervical, lumbar, knee, hip and hands) in Spain. Lumbar spine osteoarthritis is the most prevalent.EPISER2016 ha sido financiado por Celgene, Laboratorios, Gebro Pharma, Merck Sharp and Dohme de España, Pfizer y Sanofi-Aventis. Los financiadores no han intervenido en el diseño del estudio, recogida ni análisis de datos, ni en la redacción de este artículo. IRP yMS fueron financiados con programas Miguel Servet II y Contrato Río Hortega-Fondo de Investigación Sanitaria (CPII17/00026 y CM17/00101), respectivamente. El Fondo de Investigación Sanitaria, integrado en el Plan Nacional de Programa Científico, Desarrollo e Innovación Tecnológica 2013-2016, es financiado por el ISCIII-Subdirección General de Evaluación y Promoción de la Investigación-Fondo Europeo de Desarrollo Regional (FEDER) «Una forma de hacer Europa

Prevalence of Symptomatic Axial Osteoarthritis Phenotypes in Spain and Associated Socio-Demographic, Anthropometric, and Lifestyle Variables

Epidemiology of RMDFinanciado para publicación en acceso aberto: Universidade da Coruña/CISUG[Abstract] Objective. Axial osteoarthritis (OA) is a common cause of back and neck pain, however, few studies have examined its prevalence. The aim was to estimate the prevalence and the characteristics of symptomatic axial OA in Spain. Methods. EPISER2016 is a cross-sectional multicenter population-based study of people aged 40 years or older. Subjects were randomly selected using multistage stratified cluster sampling. Participants were contacted by telephone to complete rheumatic disease screening questionnaires. Two phenotypes were analyzed, patients with Non-exclusive axial OA (NEA-OA) and Exclusive axial OA (EA-OA). To calculate the prevalence and its 95% confidence interval (CI), the sample design was considered and weighting was calculated according to age, sex and geographic origin. Results. Prevalence of NEA-OA by clinical or clinical-radiographic criteria was 19.17% (95% CI: 17.82–20.59). The frequency of NEA-OA increased with age (being 3.6 times more likely in patients aged 80 s or more than in those between 40 and 49 years) and body mass index. It was significantly more frequent in women, as well as in the center of Spain. It was less frequent in those with a higher level of education. Lumbar OA was more frequent than cervical OA. This difference grew with increasing age and was not associated with gender. It was also greater in overweight and obese subjects. Conclusions. This is the first study on the prevalence of axial OA phenotypes in Europe describing the associated socio-demographic, anthropometric, and lifestyle variables.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. EPISER2016 was supported by Celgene, Gebro Pharma, Merck Sharp & Dohme in Spain, Pfizer, and Sanofi-Aventis, none of whom had any role in the study design, data collection, data analysis, interpretation, or writing of this manuscript. MS was financed via the Rio Hortega Contract—Health Research Fund (CM17/00101), the Sanitary Research Fund integrated in the National Plan of Scientific Program, Technological Development and Innovation 2013–2016 and funded by the ISCIII-Subdirectorate General Evaluation and Promotion of Research-European Regional Development Fund (ERDF) "A way of making Europe

Inactivacion de virus ADN envueltos en la producción de hemoderivados (Albúmina e Inmunoglobulinas)

Se estudió la inactivación del virus herpes simple humano tipo 1 como modelo de virus ADN envueltos, durante las etapas de producción de las inmunoglobulinas intramuscular e intravenosa y la albúmina humana, las etapas del método de fraccionamiento alcohólico para la obtención de estos productos, así como los métodos de remoción y/o inactivación introducidos en el proceso de manufactura, pasteurización y cromatografía de intercambio iónico. El virus se cuantificó por efecto citopático. La obtención de valores de reducción acumulativos reportados en este trabajo demuestran que el método de fraccionamiento alcohólico utilizado en Cuba como variante del método de Cohn-Oncley, combinando métodos de inactivación/remoción, produce un nivel de inactivación de virus ADN envueltos que garantiza una alta seguridad biológica de estos productos para su uso en humanos.<br>Inactivation of human herpes simplex virus I asa model of enveloped DNA virus was studied in the stages of production of intramuscular/ intravenous inmunoglobulins and human albumin, in the phases of alcohol fractionation for obtaining these products, and in the methods of removal and/or inactivation implemented in manufacture, pasteurization and ion - exchange chromatography. The virus was quantified by cytophatic effects. The cumulative reduction values reported in this paper proved that the use of alcohol fractionation in Cuba, as a variant of Cohn - Oncley method, combined with removal/inactivation procedures resulted in enveloped DNA virus inactivation assuring high biological safety for albumin and immunoglobulins for their use in human beings

Prevalencia de artrosis sintomática en España: Estudio EPISER2016

Introduction: The Spanish Society of Rheumatology carried out the EPISER2000 study in 2000 to determine the prevalence of osteoarthritis and other rheumatic diseases in the Spanish population. Recent sociodemographic changes and lifestyle habits in Spain justified updating the epidemiological data on osteoarthritis and other rheumatic diseases (EPISER2016-study). Objective: To estimate the prevalence of symptomatic osteoarthritis of the cervical spine, lumbar spine, hip, knee and hand in the adult population in Spain. Material and methods: Cross-sectional population-based study. A multistage and stratified random cluster sampling was carried out. The participants were contacted by telephone to complete an osteoarthritis screening questionnaire. A rheumatologist confirmed or discarded the diagnosis. The ACR-clinical-criteria were used to diagnose hand-osteoarthritis and the ACR-clinical-radiological criteria to diagnose knee- and hip-osteoarthritis. To estimate the prevalence and its 95% confidence interval, weights were calculated according to the probability of selection in each of the sampling stages. Results: The prevalence of osteoarthritis in Spain in one or more of the locations studied was 29.35%. The prevalence of cervical-osteoarthritis was 10.10% and of lumbar-osteoarthritis 15.52%. Both are more frequent in women and at older ages, as well as in people with low levels of education and obesity. The prevalence of hip-osteoarthritis was 5.13%, that of knee-osteoarthritis 13.83%, these are associated with female sex, overweight and obesity. The prevalence of hand osteoarthritis was 7.73%. It is more frequent in women, who are obese, with a low educational level and who are older. Conclusion: The EPISER2016 study is the first to analyse the prevalence of symptomatic osteoarthritis in 5 locations (cervical, lumbar, knee, hip and hands) in Spain. Lumbar spine osteoarthritis is the most prevalent

Cesària d'una vaca

Títol a la caràtula: Tècniques de cesària en vaque