Identification of CRF66_BF, a New HIV-1 Circulating Recombinant Form of South American Origin

Circulating recombinant forms (CRFs) are important components of the HIV-1 pandemic. Among 110 reported in the literature, 17 are BF1 intersubtype recombinant, most of which are of South American origin. Among these, all 5 identified in the Southern Cone and neighboring countries, except Brazil, derive from a common recombinant ancestor related to CRF12_BF, which circulates widely in Argentina, as deduced from coincident breakpoints and clustering in phylogenetic trees. In a HIV-1 molecular epidemiological study in Spain, we identified a phylogenetic cluster of 20 samples from 3 separate regions which were of F1 subsubtype, related to the Brazilian strain, in protease-reverse transcriptase (Pr-RT) and of subtype B in integrase. Remarkably, 14 individuals from this cluster (designated BF9) were Paraguayans and only 4 were native Spaniards. HIV-1 transmission was predominantly heterosexual, except for a subcluster of 6 individuals, 5 of which were men who have sex with men. Ten additional database sequences, from Argentina (n = 4), Spain (n = 3), Paraguay (n = 1), Brazil (n = 1), and Italy (n = 1), branched within the BF9 cluster. To determine whether it represents a new CRF, near full-length genome (NFLG) sequences were obtained for 6 viruses from 3 Spanish regions. Bootscan analyses showed a coincident BF1 recombinant structure, with 5 breakpoints, located in p17 gag , integrase, gp120, gp41-rev overlap, and nef, which was identical to that of two BF1 recombinant viruses from Paraguay previously sequenced in NFLGs. Interestingly, none of the breakpoints coincided with those of CRF12_BF. In a maximum likelihood phylogenetic tree, all 8 NFLG sequences grouped in a strongly supported clade segregating from previously identified CRFs and from the CRF12_BF "family" clade. These results allow us to identify a new HIV-1 CRF, designated CRF66_BF. Through a Bayesian coalescent analysis, the most recent common ancestor of CRF66_BF was estimated around 1984 in South America, either in Paraguay or Argentina. Among Pr-RT sequences obtained by us from HIV-1-infected Paraguayans living in Spain, 14 (20.9%) of 67 were of CRF66_BF, suggesting that CRF66_BF may be one of the major HIV-1 genetic forms circulating in Paraguay. CRF66_BF is the first reported non-Brazilian South American HIV-1 CRF_BF unrelated to CRF12_BF.This work was funded through Acción Estratégica en Salud Intramural (AESI), Instituto de Salud Carlos III, projects PI16CIII/00033 and PI19CIII/00042; Red de Investigación en SIDA (RIS), Instituto de Salud Carlos III, Subdirección General de Evaluación y Fondo Europeo de Desarrollo Regional (FEDER), Plan Nacional I+D+I, project RD16ISCIII/0002/0004; and scientific agreements with Consellería de Sanidade, Government of Galicia (MVI 1004/16) and Osakidetza-Servicio Vasco de Salud, Government of Basque Country (MVI 1001/16).S

Flow cytometry for fast screening and automated risk assessment in systemic light-chain amyloidosis

Early diagnosis and risk stratification are key to improve outcomes in light-chain (AL) amyloidosis. Here we used multidimensional-flow-cytometry (MFC) to characterize bone marrow (BM) plasma cells (PCs) from a series of 166 patients including newly-diagnosed AL amyloidosis (N = 94), MGUS (N = 20) and multiple myeloma (MM, N = 52) vs. healthy adults (N = 30). MFC detected clonality in virtually all AL amyloidosis (99%) patients. Furthermore, we developed an automated risk-stratification system based on BMPCs features, with independent prognostic impact on progression-free and overall survival of AL amyloidosis patients (hazard ratio: ≥ 2.9;P ≤ .03). Simultaneous assessment of the clonal PCs immunophenotypic protein expression profile and the BM cellular composition, mapped AL amyloidosis in the crossroad between MGUS and MM; however, lack of homogenously-positive CD56 expression, reduction of B-cell precursors and a predominantly-clonal PC compartment in the absence of an MM-like tumor PC expansion, emerged as hallmarks of AL amyloidosis (ROC-AUC = 0.74;P < .001), and might potentially be used as biomarkers for the identification of MGUS and MM patients, who are candidates for monitoring pre-symptomatic organ damage related to AL amyloidosis. Altogether, this study addressed the need for consensus on how to use flow cytometry in AL amyloidosis, and proposes a standardized MFC-based automated risk classification ready for implementation in clinical practice

Bringing inclusivity to robotics with INBOTS

Peer reviewe

Curso Didáctica de la Comunicación audiovisual

El objetivo del curso es permitir a los profesores que imparten la asignatura EATP de Imagen y Sonido en Educación Secundaria intercambiar experiencias, programaciones e ideas, para mejorar la calidad de la enseñanza. Cada uno de los asistentes al curso presenta una ponencia en la que expone su programa curricular. Explican los objetivos, los contenidos, la metodología y los materiales necesarios. Algunas de las materias tratadas son la radio, la cinematografía, el vídeo, la imagen, la publicidad, la prensa, la televisión y los medios de comunicación de masas en general.Madrid (Comunidad Autónoma). Dirección General de Educación. Servicio de Renovación PedagógicaMadridMadrid (Comunidad Autónoma). Subdirección General de Formación del Profesorado. CRIF Las Acacias; General Ricardos 179 - 28025 Madrid; Tel. + 34915250893ES

Flow cytometry for fast screening and automated risk assessment in systemic light-chain amyloidosis

Early diagnosis and risk stratification are key to improve outcomes in light-chain (AL) amyloidosis. Here we used multidimensional-flow-cytometry (MFC) to characterize bone marrow (BM) plasma cells (PCs) from a series of 166 patients including newly-diagnosed AL amyloidosis (N = 94), MGUS (N = 20) and multiple myeloma (MM, N = 52) vs. healthy adults (N = 30). MFC detected clonality in virtually all AL amyloidosis (99%) patients. Furthermore, we developed an automated risk-stratification system based on BMPCs features, with independent prognostic impact on progression-free and overall survival of AL amyloidosis patients (hazard ratio: ≥ 2.9;P ≤.03). Simultaneous assessment of the clonal PCs immunophenotypic protein expression profile and the BM cellular composition, mapped AL amyloidosis in the crossroad between MGUS and MM; however, lack of homogenously-positive CD56 expression, reduction of B-cell precursors and a predominantly-clonal PC compartment in the absence of an MM-like tumor PC expansion, emerged as hallmarks of AL amyloidosis (ROC-AUC = 0.74;P <.001), and might potentially be used as biomarkers for the identification of MGUS and MM patients, who are candidates for monitoring pre-symptomatic organ damage related to AL amyloidosis. Altogether, this study addressed the need for consensus on how to use flow cytometry in AL amyloidosis, and proposes a standardized MFC-based automated risk classification ready for implementation in clinical practice.This study was supported by the Centro de Investigación Biomédica en Red – Área de Oncología—del Instituto de Salud Carlos III (CIBERONC; CB16/12/00369, CB16/12/00400 and CB16/12/00489), Instituto de Salud Carlos III/Subdirección General de Investigación Sanitaria (FIS No. PI13/02196), Asociación Española Contra el Cáncer (GCB120981SAN and Accelerator Award), the Black Swan Research Initiative of the International Myeloma Foundation, and the European Research Council (ERC) 2015 Starting Grant (MYELOMANEXT)

New Algorithms Improving PML Risk Stratification in MS Patients Treated With Natalizumab

none60siOverview: We assessed the role of age and disease activity as new factors contributing to establish the risk of progressive multifocal leucoencephalopathy in multiple sclerosis patients treated with natalizumab in 36 University Hospitals in Europe. We performed the study in 1,307 multiple sclerosis patients (70.8% anti-John Cunninghan virus positive antibodies) treated with natalizumab for a median time of 3.28 years. Epidemiological, clinical, and laboratory variables were collected. Lipid-specific IgM oligoclonal band status was available in 277 patients. Factors associated with progressive multifocal leucoencephalopathy onset were explored by uni- and multivariate logistic regression. Results: Thirty-five patients developed progressive multifocal leucoencephalopathy. The multivariate analysis identified anti-John Cunninghan virus antibody indices and relapse rate as the best predictors for the onset of this serious opportunistic infection in the whole cohort. They allowed to stratify progressive multifocal leucoencephalopathy risk before natalizumab initiation in individual patients [area under the curve (AUC) = 0.85]. The risk ranged from &lt;1/3,300 in patients with anti-John Cunninghan virus antibody indices &lt;0.9 and relapse rate &gt;0.5, to 1/50 in the opposite case. In patients with lipid-specific IgM oligoclonal bands assessment, age at natalizumab onset, anti-John Cunninghan virus antibody indices, and lipid-specific IgM oligoclonal band status predicted progressive multifocal leucoencephalopathy risk (AUC = 0.92). The absence of lipid-specific IgM oligoclonal bands was the best individual predictor (OR = 40.94). The individual risk ranged from &lt;1/10,000 in patients younger than 45 years at natalizumab initiation, who showed anti John Cunningham virus antibody indices &lt;0.9 and lipid-specific IgM oligoclonal bands to 1/33 in the opposite case. Conclusions: In a perspective of personalized medicine, disease activity, anti-lipid specific IgM oligoclonal bands, anti Jonh Cunninghan virus antibody levels, and age can help tailor natalizumab therapy in multiple sclerosis patients, as predictors of progressive multifocal leucoencephalopathy.mixedToboso, Inmaculada; Tejeda-Velarde, Amalia; Alvarez-Lafuente, Roberto; Arroyo, Rafael; Hegen, Harald; Deisenhammer, Florian; Sainz de la Maza, Susana; Alvarez-Cermeño, José C; Izquierdo, Guillermo; Paramo, Dolores; Oliva, Pedro; Casanova, Bonaventura; Agüera-Morales, Eduardo; Franciotta, Diego; Gastaldi, Matteo; Fernández, Oscar; Urbaneja, Patricia; Garcia-Dominguez, José M; Romero, Fernando; Laroni, Alice; Uccelli, Antonio; Perez-Sempere, Angel; Saiz, Albert; Blanco, Yolanda; Galimberti, Daniela; Scarpini, Elio; Espejo, Carmen; Montalban, Xavier; Rasche, Ludwig; Paul, Friedemann; González, Inés; Álvarez, Elena; Ramo, Cristina; Caminero, Ana B; Aladro, Yolanda; Calles, Carmen; Eguía, Pablo; Belenguer-Benavides, Antonio; Ramió-Torrentà, Lluis; Quintana, Ester; Martínez-Rodríguez, José E; Oterino, Agustín; López de Silanes, Carlos; Casanova, Luis I; Landete, Lamberto; Frederiksen, Jette; Bsteh, Gabriel; Mulero, Patricia; Comabella, Manuel; Hernández, Miguel A; Espiño, Mercedes; Prieto, José M; Pérez, Domingo; Otano, María; Padilla, Francisco; García-Merino, Juan A; Navarro, Laura; Muriel, Alfonso; Frossard, Lucienne Costa; Villar, Luisa MToboso, Inmaculada; Tejeda-Velarde, Amalia; Alvarez-Lafuente, Roberto; Arroyo, Rafael; Hegen, Harald; Deisenhammer, Florian; Sainz de la Maza, Susana; Alvarez-Cermeño, José C; Izquierdo, Guillermo; Paramo, Dolores; Oliva, Pedro; Casanova, Bonaventura; Agüera-Morales, Eduardo; Franciotta, Diego; Gastaldi, Matteo; Fernández, Oscar; Urbaneja, Patricia; Garcia-Dominguez, José M; Romero, Fernando; Laroni, Alice; Uccelli, Antonio; Perez-Sempere, Angel; Saiz, Albert; Blanco, Yolanda; Galimberti, Daniela; Scarpini, Elio; Espejo, Carmen; Montalban, Xavier; Rasche, Ludwig; Paul, Friedemann; González, Inés; Álvarez, Elena; Ramo, Cristina; Caminero, Ana B; Aladro, Yolanda; Calles, Carmen; Eguía, Pablo; Belenguer-Benavides, Antonio; Ramió-Torrentà, Lluis; Quintana, Ester; Martínez-Rodríguez, José E; Oterino, Agustín; López de Silanes, Carlos; Casanova, Luis I; Landete, Lamberto; Frederiksen, Jette; Bsteh, Gabriel; Mulero, Patricia; Comabella, Manuel; Hernández, Miguel A; Espiño, Mercedes; Prieto, José M; Pérez, Domingo; Otano, María; Padilla, Francisco; García-Merino, Juan A; Navarro, Laura; Muriel, Alfonso; Frossard, Lucienne Costa; Villar, Luisa

New Algorithms Improving PML Risk Stratification in MS Patients Treated With Natalizumab

Overview: We assessed the role of age and disease activity as new factors contributing to establish the risk of progressive multifocal leucoencephalopathy in multiple sclerosis patients treated with natalizumab in 36 University Hospitals in Europe. We performed the study in 1,307 multiple sclerosis patients (70.8% anti-John Cunninghan virus positive antibodies) treated with natalizumab for a median time of 3.28 years. Epidemiological, clinical, and laboratory variables were collected. Lipid-specific IgM oligoclonal band status was available in 277 patients. Factors associated with progressive multifocal leucoencephalopathy onset were explored by uni- and multivariate logistic regression. Results: Thirty-five patients developed progressive multifocal leucoencephalopathy. The multivariate analysis identified anti-John Cunninghan virus antibody indices and relapse rate as the best predictors for the onset of this serious opportunistic infection in the whole cohort. They allowed to stratify progressive multifocal leucoencephalopathy risk before natalizumab initiation in individual patients [area under the curve (AUC) = 0.85]. The risk ranged from 0.5, to 1/50 in the opposite case. In patients with lipid-specific IgM oligoclonal bands assessment, age at natalizumab onset, anti-John Cunninghan virus antibody indices, and lipid-specific IgM oligoclonal band status predicted progressive multifocal leucoencephalopathy risk (AUC = 0.92). The absence of lipid-specific IgM oligoclonal bands was the best individual predictor (OR = 40.94). The individual risk ranged from <1/10,000 in patients younger than 45 years at natalizumab initiation, who showed anti John Cunningham virus antibody indices <0.9 and lipid-specific IgM oligoclonal bands to 1/33 in the opposite case. Conclusions: In a perspective of personalized medicine, disease activity, anti-lipid specific IgM oligoclonal bands, anti Jonh Cunninghan virus antibody levels, and age can help tailor natalizumab therapy in multiple sclerosis patients, as predictors of progressive multifocal leucoencephalopath

El parque de Yuncos como espacio educativo y recreativo

Resumen basado en el del proyecto. Premiado en la convocatoria: Premios para proyectos de innovación concluidos durante el curso 2006-2007, en los centros educativos no universitarios sostenidos con fondos públicos de la Comunidad Autónoma de Castilla-La Mancha (Orden 30-01-2008, de la Consejería de Educación y Ciencia de la Junta de Comunidades de Castilla-La Mancha. Resolución de 15-05-2009, de la Viceconsejería de Educación)El proyecto desarrolla una serie de actividades de enseñanza y aprendizaje en el campo de la educación ambiental basadas en el principio de la investigación recreativa. Las actividades se realizan en un parque municipal. Programadas por profesores del Instituto y del Colegio Público, en colaboración con el Ayuntamiento del municipio, dirigidas a alumnos de Primaria, e impartidas por alumnos de Secundaria, que intervienen como monitores. Los objetivos básicos que se persiguen son: mejorar la comunicación educativa entre centros de Primaria y de Secundaria, mediante el diseño compartido de actividades de enseñanza y aprendizaje, integrando conocimientos, planteamientos y experiencias docentes diferentes. Se persigue así una cooperación real y eficaz entre un Colegio y un Instituto de un mismo municipio, a partir de la colaboración en tareas comunes. Colaboración, a la que se suma el Ayuntamiento, facilitando aspectos logísticos y espacios necesarios para llevar a cabo las actividades programadas. En segundo lugar, incorporar al alumnado de secundaria en el proceso educativo como docente, impartiendo y adaptando actividades dirigidas a alumnos de niveles inferiores, como estrategia para lograr aprendizajes significativos y funcionales. El tercer objetivo es abordar la educación ambiental, explorando actividades con metodologías educativas basadas en el principio de la investigación recreativa con el objetivo de favorecer la adquisición de valores y conductas de respeto al medio ambiente. La metodología de trabajo se basa en el principio educativo de aprender a aprender, favoreciendo estrategias de aprendizaje a través del descubrimiento y de la interacción y facilitando la consecución de aprendizajes funcionales. La organización de las tareas se plantea a partir de un aprendizaje en grupos, que favorece las relaciones entre iguales y la superación de conflictos mediante el diálogo y la cooperación.Castilla La ManchaConsejería de Educación, Ciencia y Cultura. Viceconsejería de Educación y Cultura. Servicio de Documentación; Bulevar del Río Alberche, s. n. - 1 Planta; 45071 Toledo; Tel. +34925286045; Fax +34925247410; [email protected]