Defibrotide inhibits donor leucocyte-endothelial interactions and protects against acute graft-versus-host disease

Altres ajuts: This study has been funded by Josep Carreras Leukaemia Foundation (Grant 11R/2016 and 03R/2019).Allogeneic hematopoietic stem cell transplantation (allo-HCT) is an effective therapy for the treatment of high-risk haematological malignant disorders and other life-threatening haematological and genetic diseases. Acute graft-versus-host disease (aGvHD) remains the most frequent cause of non-relapse mortality following allo-HCT and limits its extensive clinical application. Current pharmacologic agents used for prophylaxis and treatment of aGvHD are not uniformly successful and have serious secondary side effects. Therefore, more effective and safe prophylaxis and therapy for aGvHD are an unmet clinical need. Defibrotide is a multi-target drug successfully employed for prophylaxis and treatment of veno-occlusive disease/sinusoidal obstruction syndrome. Recent preliminary clinical data have suggested some efficacy of defibrotide in the prevention of aGvHD after allo-HCT. Using a fully MHC-mismatched murine model of allo-HCT, we report here that defibrotide, either in prophylaxis or treatment, is effective in preventing T cell and neutrophil infiltration and aGvHD-associated tissue injury, thus reducing aGvHD incidence and severity, with significantly improved survival after allo-HCT. Moreover, we performed in vitro mechanistic studies using human cells revealing that defibrotide inhibits leucocyte-endothelial interactions by down-regulating expression of key endothelial adhesion molecules involved in leucocyte trafficking. Together, these findings provide evidence that defibrotide may represent an effective and safe clinical alternative for both prophylaxis and treatment of aGvHD after allo-HCT, paving the way for new therapeutic approaches

CONFIDENCE overview of improvements in radioecological human food chain models and future needs

Radioecological models used to make predictions of the radionuclide activity concentrations in human foodstuffs must be sufficiently robust and fit for purpose with uncertainties reduced where practicable. The CONFIDENCE project had a work package with the objective to improve the capabilities of radioecological models and this paper presents the key findings of this work. Recommendations for future radioecological studies/model developments are made based on the findings of the work conducted and consultations with end-users

FTO gene: Historic background and its relationship with chronic-degenerative diseases

Indexación: Scopus; Latindex.Alteraciones en el desarrollo de la atención y la organización conductual pueden configurar cuadros clínicos como el trastorno déficit de atención (TDA) que puede estar acompañado o no de hiperactividad (TDAH), este último parece tener una relación directa con otros diagnósticos de tipo endocrino como la obesidad. El objetivo del estudio es analizar la relación que existe entre el TDAH y la obesidad. Es por ello que se realiza una revisión sistemática de estudios científicos revelando relaciones y diferencias entre ambos trastornos desde una mirada fisiológica, cognoscitiva y comportamental. Se concluye que la relación entre el TDAH y la obesidad se da por factores genéticos, por variaciones dopaminérgicas, cambios en patrones de sueño, desajustes emocionales y por alteraciones en la regulación de la conducta; igualmente influyen factores sociales relacionados con el cuidado en el embarazo y la alimentación de las mujeres antes y durante la gestación.http://www.revhipertension.com/rlh_2_2018/5_fto_gene.pd

Novel genetic loci associated with hippocampal volume

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

Atlas de las praderas marinas de España

Knowledge of the distribution and extent of seagrass habitats is currently the basis of management and conservation policies of the coastal zones in most European countries. This basic information is being requested through European directives for the establishment of monitoring programmes and the implementation of specific actions to preserve the marine environment. In addition, this information is crucial for the quantification of the ecological importance usually attributed to seagrass habitats due to, for instance, their involvement in biogeochemical cycles, marine biodiversity and quality of coastal waters or global carbon budgets. The seagrass atlas of Spain represents a huge collective effort performed by 84 authors across 30 Spanish institutions largely involved in the scientific research, management and conservation of seagrass habitats during the last three decades. They have contributed to the availability of the most precise and realistic seagrass maps for each region of the Spanish coast which have been integrated in a GIS to obtain the distribution and area of each seagrass species. Most of this information has independently originated at a regional level by regional governments, universities and public research organisations, which explain the elevated heterogeneity in criteria, scales, methods and objectives of the available information. On this basis, seagrass habitats in Spain occupy a total surface of 1,541,63 km2, 89% of which is concentrated in the Mediterranean regions; the rest is present in sheltered estuarine areas of the Atlantic peninsular regions and in the open coastal waters of the Canary Islands, which represents 50% of the Atlantic meadows. Of this surface, 71.5% corresponds to Posidonia oceanica, 19.5% to Cymodocea nodosa, 3.1% to Zostera noltii (=Nanozostera noltii), 0.3% to Zostera marina and 1.2% to Halophila decipiens. Species distribution maps are presented (including Ruppia spp.), together with maps of the main impacts and pressures that has affected or threatened their conservation status, as well as the management tools established for their protection and conservation. Despite this considerable effort, and the fact that Spain has mapped wide shelf areas, the information available is still incomplete and with weak precision in many regions, which will require an investment of major effort in the near future to complete the whole picture and respond to demands of EU directives

Atlas de las praderas marinas de España

Knowledge of the distribution and extent of seagrass habitats is currently the basis of management and conservation policies of the coastal zones in most European countries. This basic information is being requested through European directives for the establishment of monitoring programmes and the implementation of specific actions to preserve the marine environment. In addition, this information is crucial for the quantification of the ecological importance usually attributed to seagrass habitats due to, for instance, their involvement in biogeochemical cycles, marine biodiversity and quality of coastal waters or global carbon budgets. The seagrass atlas of Spain represents a huge collective effort performed by 84 authors across 30 Spanish institutions largely involved in the scientific research, management and conservation of seagrass habitats during the last three decades. They have contributed to the availability of the most precise and realistic seagrass maps for each region of the Spanish coast which have been integrated in a GIS to obtain the distribution and area of each seagrass species. Most of this information has independently originated at a regional level by regional governments, universities and public research organisations, which explain the elevated heterogeneity in criteria, scales, methods and objectives of the available information. On this basis, seagrass habitats in Spain occupy a total surface of 1,541,63 km2, 89% of which is concentrated in the Mediterranean regions; the rest is present in sheltered estuarine areas of the Atlantic peninsular regions and in the open coastal waters of the Canary Islands, which represents 50% of the Atlantic meadows. Of this surface, 71.5% corresponds to Posidonia oceanica, 19.5% to Cymodocea nodosa, 3.1% to Zostera noltii (=Nanozostera noltii), 0.3% to Zostera marina and 1.2% to Halophila decipiens. Species distribution maps are presented (including Ruppia spp.), together with maps of the main impacts and pressures that has affected or threatened their conservation status, as well as the management tools established for their protection and conservation. Despite this considerable effort, and the fact that Spain has mapped wide shelf areas, the information available is still incomplete and with weak precision in many regions, which will require an investment of major effort in the near future to complete the whole picture and respond to demands of EU directives.Versión del edito

Analysis of morphological changes in the Ebro submerged delta (1880-1992)

Actas de la XIV Reunión Nacional de Geomorfología Málaga, 22-25 de Junio de 2016.-- 7 pages, 6 figures, 1 table[EN] The present study approaches the analysis of the changes happened in the delta of the river Ebro from ancient cartography, bathymetries and the utilization of Digital Elevations Models (DEM). For it, there has been elaborated two DEM of the delta, one from nautical charts of the 19th century, and other one realized from recent bathymetries and the most current nautical chart (1976). By means of the program ArcMap 10.2 have compared the results of both models, which has allowed us to identify and to analyze the morphologic changes happened during this period. The zones of maximum erosion (associated with certain coastal areas and with the deltoid left lobes) and those of maximum accumulation (associated with the development of the current prodelta and with the sedimentation on the ends of the coastal arrows) are identified. These results are coherent with the knowledge on the sedimentary recent dynamics of the delta of the Ebro and allow to infer the morphologic evolution of the left long-term lobesEl presente trabajo ha sido financiado por el proyecto de investigación CGL2013-44917-R del Ministerio de Economía y Competitividad. Ha contado también con fondos FEDER.Peer Reviewe

Defibrotide inhibits donor leucocyte-endothelial interactions and protects against acute graft-versus-host disease

Altres ajuts: This study has been funded by Josep Carreras Leukaemia Foundation (Grant 11R/2016 and 03R/2019).Allogeneic hematopoietic stem cell transplantation (allo-HCT) is an effective therapy for the treatment of high-risk haematological malignant disorders and other life-threatening haematological and genetic diseases. Acute graft-versus-host disease (aGvHD) remains the most frequent cause of non-relapse mortality following allo-HCT and limits its extensive clinical application. Current pharmacologic agents used for prophylaxis and treatment of aGvHD are not uniformly successful and have serious secondary side effects. Therefore, more effective and safe prophylaxis and therapy for aGvHD are an unmet clinical need. Defibrotide is a multi-target drug successfully employed for prophylaxis and treatment of veno-occlusive disease/sinusoidal obstruction syndrome. Recent preliminary clinical data have suggested some efficacy of defibrotide in the prevention of aGvHD after allo-HCT. Using a fully MHC-mismatched murine model of allo-HCT, we report here that defibrotide, either in prophylaxis or treatment, is effective in preventing T cell and neutrophil infiltration and aGvHD-associated tissue injury, thus reducing aGvHD incidence and severity, with significantly improved survival after allo-HCT. Moreover, we performed in vitro mechanistic studies using human cells revealing that defibrotide inhibits leucocyte-endothelial interactions by down-regulating expression of key endothelial adhesion molecules involved in leucocyte trafficking. Together, these findings provide evidence that defibrotide may represent an effective and safe clinical alternative for both prophylaxis and treatment of aGvHD after allo-HCT, paving the way for new therapeutic approaches