Lmo2 expression defines tumor cell identity during T-cell leukemogenesis

The impact of LMO2 expression on cell lineage decisions during T-cell leukemogenesis remains largely elusive. Using genetic lineage tracing, we have explored the potential of LMO2 in dictating a T-cell malignant phenotype. We first initiated LMO2 expression in hematopoietic stem/progenitor cells and maintained its expression in all hematopoietic cells. These mice develop exclusively aggressive human-like T-ALL. In order to uncover a potential exclusive reprogramming effect of LMO2 in murine hematopoietic stem/progenitor cells, we next showed that transient LMO2 expression is sufficient for oncogenic function and induction of T-ALL. The resulting T-ALLs lacked LMO2 and its target-gene expression, and histologically, transcriptionally, and genetically similar to human LMO2-driven T-ALL. We next found that during T-ALL development, secondary genomic alterations take place within the thymus. However, the permissiveness for development of T-ALL seems to be associated with wider windows of differentiation than previously appreciated. Restricted Cre-mediated activation of Lmo2 at different stages of B-cell development induces systematically and unexpectedly T-ALL that closely resembled those of their natural counterparts. Together, these results provide a novel paradigm for the generation of tumor T cells through reprogramming in vivo and could be relevant to improve the response of T-ALL to current therapies.J.H. has been supported by the German Cancer Aid (Project 110997 and Translational Oncology Program 70112951), the German Jose Carreras Leukemia Foundation (DJCLS 02R/2016), Deutsches Konsortium für Translationale Krebsforschung (DKTK), Joint funding (Targeting MYC L*10), the Kinderkrebsstiftung (2016/17), and the “Elterninitiative Kinderkrebsklinik e.V. Düsseldorf”. SG has been supported by a scholarship of the Hochschule Bonn-Rhein-Sieg. AB has been supported by the German Children's Cancer Foundation and the Federal Ministry of Education and Research, Bonn, Germany. Research in ISG group is partially supported by FEDER and by MINECO (SAF2012-32810, SAF2015-64420-R, and Red de Excelencia Consolider OncoBIO SAF2014-57791-REDC), Instituto de Salud Carlos III (PIE14/00066), ISCIII- Plan de Ayudas IBSAL 2015 Proyectos Integrados (IBY15/00003), by Junta de Castilla y León (BIO/SA51/15, CSI001U14, UIC-017, and CSI001U16), Fundacion Inocente Inocente, and by the ARIMMORA project (European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 282891). ISG Lab is a member of the EuroSyStem and the DECIDE Network funded by the European Union under the FP7 program. AB and ISG have been supported by the German Carreras Foundation (DJCLS R13/26). IGR was supported by BES-Ministerio de Economía y Competitividad (BES-2013-063789). AML and GRH were supported by FSE-Conserjería de Educación de la Junta de Castilla y León (CSI001-13, CSI001-15). Research in CVD group is partially supported by FEDER, “Miguel Servet” Grant (CP14/00082—AES 2013-2016) from the Instituto de Salud Carlos III (Ministerio de Economía y Competitividad), “Fondo de Investigaciones Sanitarias/Instituto de Salud Carlos III” (PI17/00167), and by the Lady Tata International Award for Research in Leukaemia 2016–2017

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

Vocabulario de la sociedad civil, la ruralidad y los movimientos sociales en América Latina

El Vocabulario de la Sociedad Civil, la Ruralidad y los Movimientos Sociales en América Latina tiene como objetivo desarrollar vocablos relacionados con temas de gran trascendencia para la vida colectiva de la población Latinoamericana; pretende introducir a estudiantes, personas del ámbito académico y activistas en la comprensión de estas categorías de análisis. A través de la mirada de 70 especialistas que participaron en este vocabulario, es posible comprender muchos de los términos que se utilizan dentro de la investigación social y áreas relacionadas con las ciencias políticas, ambientales y rurales, a partir de una mayor explicación y detalle. Es por ello que se inserta este trabajo desde una mirada colectiva y amplia de los conceptos que se exponen. En este libro podrá encontrar las ideas de varios autores y autoras de distintas universidades, con una visión multi, inter y transdisciplinaria. El esfuerzo que se realizó para conjuntar varios términos y analizar su compleja red de interpretaciones, permitirá que este manuscrito pueda ser consultado por estudiantes, personas del ámbito científico-académico, y ciudadanía; porque contiene el estado del arte, la historia del paulatino avance de múltiples conceptos y su vigencia en el contexto actual

Population structure of the red-legged partridge: management implications

Resumen del póster presentado al XXXth International Union of Game Biologists and Perdix XIII, celebrados en Barcelona (España) del 5 al 9 de septiembre de 2011.Dispersal barriers may arise and disappear repeatedly over the course of a species’ distribution and can have different effects depending partially on the duration of the barrier and the species’ ecology. The red-legged partridge (Alectoris rufa) has a large natural distribution range extending from the Mediterranean to humid temperate zones. However, the genetic structure of this species is unknown. We investigated the potential impact of Pleistocene and Holocene range shifts on the phylogeographic patterns and genetic population structure of this species using mitochondrial DNA control-region and nuclear microsatellite loci. Our results imply that during the Pleistocene glaciations this species was affected by climatic changes and ephemeral geographic barriers, which led to their current shallow genealogical and genetic structure apportioned into five genetic groups: South-western, Central-eastern, North-western, Balearic, and French and Italian, which could be recognized as management units (stocks) of the A. rufa species. Future conservation and management plans of this species should take into account its wild genetic structure in regards of releases of captivebred partridges for restocking, avoiding the mixture of different gene pools and alteration of intraspecific diversity.Peer Reviewe

Phylogeography and genetic structure of the red-legged partridge (Alectoris rufa): more evidence for refugia within the Iberian glacial refugium

The Pleistocene climatic oscillations promoted the diversification in avian species during the last glacial period. The red-legged partridge (Alectoris rufa, Family Phasianidae) has a large natural distribution extending from the Mediterranean to humid temperate zones. However, the genetic structure for this species is unknown. The present study investigates the phylogeography, genetic structure and demographic history of A. rufa across its distribution, employing both mitochondrial DNA control region sequences and nuclear microsatellite loci. Our results propose that this species was greatly affected by Pleistocene glaciations. The mismatch analyses suggest that the current populations resulted from post-glacial expansion and subsequent differentiation resulting in five diagnosable genetic clusters: Southwestern, Central-eastern, Northwestern, Balearic and French and Italian. Further, we found evidence of three glacial refugia within the currently recognized Iberian glacial refugium. The intraspecific structure revealed by both maternal and biparental phylogeographic analyses was not resolved in the phylogenetic analyses. Based on all considerations, we recommended that five management units be recognized.This study was supported by the projects PREG05-017 and PREG07-020 granted by Junta de Comunidades de Castilla La Mancha. Over the course of this study, M.E.F. was supported by predoctoral fellowships from the Junta de Comunidades de Castilla La Mancha and the European Social Fund; J.A.B.-A. was supported by Fundaçao para a Ciencia e a Tecnologia with a postdoctoral fellowship (SFRH ⁄ BPD ⁄ 65464 ⁄ 2009).Peer Reviewe

Anestesia regional guiada por ultrasonido en territorio del nervio pudendo

Introducción: Los bloqueos del nervio pudendo poseen un amplio rango de utilidades clínicas en el manejo agudo de dolor POP en cirugía urológica, ginecológica, en coloproctología así como en Medicina del dolor en diagnóstico diferencial y manejo de las neuropatías del nervio pudendo. Sin embargo su aplicación es relativamente infrecuente a pesar de los beneficios. Objetivo: Realizar una descripción detallada de las técnicas más recientes guiadas por ultrasonografía con el objeto de motivar su aprendizaje de una manera segura y reproducible. Materiales y métodos: Se realizó una revisión amplia, no sistemática de la literatura a través de Medline, Embase y Science Direct desde 1985 hasta 2016, evaluando los artículos más relevantes, utilizando las palabras clave: anatomía del nervio pudendo, nervio pudendo, bloqueos del nervio pudendo, ultrasonido del nervio pudendo, neuralgia del pudendo, atrapamiento nervioso, dolor crónico, canal de Alcock y dolor pélvico. La búsqueda se limitó a artículos publicados en español, inglés y francés. Resultados: Se encontraron recientes descripciones de una gran cantidad de variantes anatómica, que se describen en detalle y muestran en documentos gráficos con el propósito de facilitar la correlación sonoanatómica de la localización del nervio como guía para la realización de bloqueos de nervio pudendo a través de los diferentes abordajes. Conclusiones: El conocimiento profundo y detallado de la anatomía del nervio pudendo y sus variaciones es esencial para la realización de técnicas de anestesia regional guiada por imágenes. Estas técnicas promisorias deben continuar evaluándose con estudios clínicos. © 2017 Sociedad Colombiana de Anestesiología y Reanimación.Introduction Pudendal nerve blocks have a wide range of clinical applications for the management of acute post-operative pain in urologic and gynaecologic surgery, in coloproctology, as well as in pain medicine for differential diagnosis, and for the management of pudendal neuropathies. However, despite its benefits, it is infrequently used. Objective To perform a detailed description of the most recent ultrasound-guided techniques with the aim of encouraging safe and reproducible learning. Materials and methods We have performed a broad, non-systematic review of the literature through Medline, Embase and Science Direct between 1985 and 2016, to evaluate the most relevant articles, using the following key words: pudendal nerve anatomy; pudendal nerve; pudendal nerve blocks; pudendal nerve ultrasound; pudendal neuralgia; nerve entrapment; chronic pain; Alcock canal; and pelvic pain. The search was limited to articles published in Spanish; English and French. Results Recent descriptions were found of a large number of anatomic variants, which are described in detail and shown in graphic documents in order to facilitate the sonoanatomic correlation of nerve location as a guide for the performance of the pudendal nerve block through the different approaches. Conclusions The deep and detailed knowledge of the anatomy of the pudendal nerve and its variations is essential for the realization of Regional Anesthesia techniques guided by images. These promising techniques should continue to be evaluated with clinical studies. © 2017 Sociedad Colombiana de Anestesiología y Reanimació

Anestesia regional guiada por ultrasonido en territorio del nervio pudendo

Introducción: Los bloqueos del nervio pudendo poseen un amplio rango de utilidades clínicas en el manejo agudo de dolor POP en cirugía urológica, ginecológica, en coloproctología así como en Medicina del dolor en diagnóstico diferencial y manejo de las neuropatías del nervio pudendo. Sin embargo su aplicación es relativamente infrecuente a pesar de los beneficios. Objetivo: Realizar una descripción detallada de las técnicas más recientes guiadas por ultrasonografía con el objeto de motivar su aprendizaje de una manera segura y reproducible. Materiales y métodos: Se realizó una revisión amplia, no sistemática de la literatura a través de Medline, Embase y Science Direct desde 1985 hasta 2016, evaluando los artículos más relevantes, utilizando las palabras clave: anatomía del nervio pudendo, nervio pudendo, bloqueos del nervio pudendo, ultrasonido del nervio pudendo, neuralgia del pudendo, atrapamiento nervioso, dolor crónico, canal de Alcock y dolor pélvico. La búsqueda se limitó a artículos publicados en español, inglés y francés. Resultados: Se encontraron recientes descripciones de una gran cantidad de variantes anatómica, que se describen en detalle y muestran en documentos gráficos con el propósito de facilitar la correlación sonoanatómica de la localización del nervio como guía para la realización de bloqueos de nervio pudendo a través de los diferentes abordajes. Conclusiones: El conocimiento profundo y detallado de la anatomía del nervio pudendo y sus variaciones es esencial para la realización de técnicas de anestesia regional guiada por imágenes. Estas técnicas promisorias deben continuar evaluándose con estudios clínicos. © 2017 Sociedad Colombiana de Anestesiología y Reanimación.Introduction Pudendal nerve blocks have a wide range of clinical applications for the management of acute post-operative pain in urologic and gynaecologic surgery, in coloproctology, as well as in pain medicine for differential diagnosis, and for the management of pudendal neuropathies. However, despite its benefits, it is infrequently used. Objective To perform a detailed description of the most recent ultrasound-guided techniques with the aim of encouraging safe and reproducible learning. Materials and methods We have performed a broad, non-systematic review of the literature through Medline, Embase and Science Direct between 1985 and 2016, to evaluate the most relevant articles, using the following key words: pudendal nerve anatomy; pudendal nerve; pudendal nerve blocks; pudendal nerve ultrasound; pudendal neuralgia; nerve entrapment; chronic pain; Alcock canal; and pelvic pain. The search was limited to articles published in Spanish; English and French. Results Recent descriptions were found of a large number of anatomic variants, which are described in detail and shown in graphic documents in order to facilitate the sonoanatomic correlation of nerve location as a guide for the performance of the pudendal nerve block through the different approaches. Conclusions The deep and detailed knowledge of the anatomy of the pudendal nerve and its variations is essential for the realization of Regional Anesthesia techniques guided by images. These promising techniques should continue to be evaluated with clinical studies. © 2017 Sociedad Colombiana de Anestesiología y Reanimació

Lmo2 expression defines tumor cell identity during T-cell leukemogenesis

The impact of LMO2 expression on cell lineage decisions during T-cell leukemogenesis remains largely elusive. Using genetic lineage tracing, we have explored the potential of LMO2 in dictating a T-cell malignant phenotype. We first initiated LMO2 expression in hematopoietic stem/progenitor cells and maintained its expression in all hematopoietic cells. These mice develop exclusively aggressive human-like T-ALL In order to uncover a potential exclusive reprogramming effect of LMO2 in murine hematopoietic stem/progenitor cells, we next showed that transient LMO2 expression is sufficient for oncogenic function and induction of T-ALL The resulting T-ALLs lacked LMO2 and its target-gene expression, and histologically, transcriptionally, and genetically similar to human LMO2-driven T-ALL We next found that during T-ALL development, secondary genomic alterations take place within the thymus. However, the permissiveness for development of T-ALL seems to be associated with wider windows of differentiation than previously appreciated. Restricted Cre-mediated activation of at different stages of B-cell development induces systematically and unexpectedly T-ALL that closely resembled those of their natural counterparts. Together, these results provide a novel paradigm for the generation of tumor T cells through reprogramming and could be relevant to improve the response of T-ALL to current therapies