Amelioration of Ischemic brain damage by peritoneal dialysis

Ischemic stroke is a devastating condition, for which there is still no effective therapy. Acute ischemic stroke is associated with high concentrations of glutamate in the blood and interstitial brain fluid. The inability of the tissue to retain glutamate within the cells of the brain ultimately provokes neuronal death. Increased concentrations of interstitial glutamate exert further excitotoxic effects on healthy tissue surrounding the infarct zone. We developed a strategy based on peritoneal dialysis to reduce blood glutamate levels, thereby accelerating brain-to-blood glutamate clearance. In a rat model of stroke, this simple procedure reduced the transient increase in glutamate, consequently decreasing the size of the infarct area. Functional magnetic resonance imaging demonstrated that the rescued brain tissue remained functional. Moreover, in patients with kidney failure, peritoneal dialysis significantly decreased glutamate concentrations. Our results suggest that peritoneal dialysis may represent a simple and effective intervention for human stroke patientsThis work was supported by grants from the Spanish MINECO to J. Sánchez-Prieto (BFU2010/16947), I. Lizasoain (SAF2011- 23354), and M.A. Moro (SAF2009-08145, SAF2012-33216, and CSD2010-00045); from Fondo Europeo de Desarrollo Regional (FEDER) “Instituto de Salud Carlos III” (RD06/0026, RD12/0014) to I. Lizasoain, M. Torres, J. Vivancos, and J. Sánchez-Prieto; from the “Comunidad de Madrid” (CAM-I2M2 2011-BMD-2349) to I. Lizasoain, M. Torres, J. Vivancos, and J. Sánchez-Prieto; and from NEUROSTEMCM to M.A. Moro (S2010/BMD-2336). Research in the laboratory of S. Canals and J. Lerma is supported by grants from the Spanish MINECO (BFU2009-09938, BFU2011-24084, and CSD2007-00023

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Aplicación práctica de técnicas de innovación docente para el desarrollo de habilidades directivas generales y tecnológicas

Presentamos en este trabajo un conjunto de actuaciones llevadas a cabo con el objetivo de mejorar la formación de nuestros alumnos de la Licenciatura de Administración y Dirección de Empresas de la Facultad de Ciencias Económicas y Empresariales de la Universidad de Huelva. Hemos establecido un conjunto de acciones para planificar y organizar nuestra actividad formativa utilizando como base metodológica el enfoque sistémico aplicado a la enseñanza. Innovando sobre todo en cuanto a los métodos docentes empleados y en las formas de motivación de nuestros alumnos. Habiendo contado para poder llevarlos a cabo con proyectos financiados por subvenciones para la innovación docente de la Unión Europea, del Ministerio de Educación, Cultura y Deporte y de la propia Universidad de Huelva. El principal objetivo que nos ha llevado a realizar este conjunto de acciones es intentar preparar y motivar a nuestros alumnos para su futuro desarrollo, tanto en lo personal como en lo profesional, en el nuevo contexto socioeconómico y tecnológico en el que se han de desenvolver.In this work, we present a set of measures which were carried out with the objective of improving the training of our Degree in Business Administration and Management students at the Faculty of Economic and Business Sciences of the University of Huelva. We have established a set of actions to plan and organize our training activity using the systemic focus applied to education as the methodological basis, innovating especially in terms of the teaching methods used and the forms of motivation of our students, and having taken into account to carry them out with projects financed by subsides for teaching innovation from the European Union, from the Education, Culture, and Sport Ministry, and the University of Huelva itself. The main objective which has led us to perform this set of actions is to try to prepare and motivate our students for their future development, both in personal and professional matters, in the new socioeconomic and technological context that they have to cope with

Aplicación práctica de técnicas de innovación docente para el desarrollo de habilidades directivas generales y tecnológicas

Presentamos en este trabajo un conjunto de actuaciones llevadas a cabo con el objetivo de mejorar la formación de nuestros alumnos de la Licenciatura de Administración y Dirección de Empresas de la Facultad de Ciencias Económicas y Empresariales de la Universidad de Huelva. Hemos establecido un conjunto de acciones para planificar y organizar nuestra actividad formativa utilizando como base metodológica el enfoque sistémico aplicado a la enseñanza. Innovando sobre todo en cuanto a los métodos docentes empleados y en las formas de motivación de nuestros alumnos. Habiendo contado para poder llevarlos a cabo con proyectos financiados por subvenciones para la innovación docente de la Unión Europea, del Ministerio de Educación, Cultura y Deporte y de la propia Universidad de Huelva. El principal objetivo que nos ha llevado a realizar este conjunto de acciones es intentar preparar y motivar a nuestros alumnos para su futuro desarrollo, tanto en lo personal como en lo profesional, en el nuevo contexto socioeconómico y tecnológico en el que se han de desenvolver

Abolition of aberrant neurogenesis ameliorates cognitive impairment after stroke in mice

Poststroke cognitive impairment is considered one of the main complications during the chronic phase of ischemic stroke. In the adult brain, the hippocampus regulates both encoding and retrieval of new information through adult neurogenesis. Nevertheless, the lack of predictive models and studies based on the forgetting processes hinders the understanding of memory alterations after stroke. Our aim was to explore whether poststroke neurogenesis participates in the development of long-term memory impairment. Here, we show a hippocampal neurogenesis burst that persisted 1 month after stroke and that correlated with an impaired contextual and spatial memory performance. Furthermore, we demonstrate that the enhancement of hippocampal neurogenesis after stroke by physical activity or memantine treatment weakened existing memories. More importantly, stroke-induced newborn neurons promoted an aberrant hippocampal circuitry remodeling with differential features at ipsi- and contralesional levels. Strikingly, inhibition of stroke-induced hippocampal neurogenesis by temozolomide treatment or using a genetic approach (Nestin-CreERT2/NSE-DTA mice) impeded the forgetting of old memories. These results suggest that hippocampal neurogenesis modulation could be considered as a potential approach for treatment of poststroke cognitive impairment.Spanish Ministry of Economy and Competitiveness (MINECO) (SAF2015-68632-R to MAM), the Instituto de Salud Carlos III (ISCIII) (FIS PI17/01601 to IL), and ISCIII cofinanced by the Fondo Europeo de Desarrollo Regional (FEDER) “Una manera de hacer Europa” RETICS (RD12/0014/0003 to IL), and the Canadian Institutes of Health Research (FDN143227to PWF

Cannabinoid type 2 receptor activation downregulates stroke-induced classic and alternative brain macrophage/microglial activation concomitant to neuroprotection

Background and Purpose-: Ischemic stroke continues to be one of the main causes of death worldwide. Inflammation accounts for a large part of damage in this pathology. The cannabinoid type 2 receptor (CB2R) has been proposed to have neuroprotective properties in neurological diseases. Therefore, our aim was to determine the effects of the activation of CB2R on infarct outcome and on ischemia-induced brain expression of classic and alternative markers of macrophage/microglial activation. Methods-: Swiss wild-type and CB2R knockout male mice were subjected to a permanent middle cerebral artery occlusion. Mice were treated with either a CB2R agonist (JWH-133), with or without a CB2R antagonist (SR144528) or vehicle. Infarct outcome was determined by measuring infarct volume and neurological outcome. An additional group of animals was used to assess mRNA and protein expression of CB2R, interleukin (IL)-1β, IL-6, tumor necrosis factor α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory peptide (MIP)-1α, RANTES, inducible nitric oxide synthase (iNOS), cyclooxygenase-2, IL-4, IL-10, transforming growth factor β (TGF-β), arginase I, and Ym1. Results-: Administration of JWH-133 significantly improved infarct outcome, as shown by a reduction in brain infarction and neurological impairment. This effect was reversed by the CB2R antagonist and was absent in CB2R knockout mice. Concomitantly, administration of JWH-133 led to a lower intensity of Iba1+ microglia/macrophages and a decrease in middle cerebral artery occlusion-induced gene expression of both classic (IL-6, TNF-α, MCP-1, MIP-1α, RANTES, and iNOS) and alternative mediators/markers (IL-10, TGF-β, and Ym1) of microglial/macrophage activation after permanent middle cerebral artery occlusion. Conclusions-: The inhibitory effect of CB2R on the activation of different subpopulations of microglia/macrophages may account for the protective effect of the selective CB2R agonist JWH-133 after stroke. © 2011 American Heart Association. All rights reserved.This work was supported by grants from Spanish Ministry of Science and Innovation (MICINN) SAF2009-08145 (M.A.M.), SAF2011-23354 (I.L.), SAF 2008-01106 (J.M.), and from both MICINN and Fondo Europeo de Desarrollo Regional (FEDER) grants Consolider CSD2010-00045 (M.A.M.) and Red Neurovascular (RENEVAS) RD06/0026/0005 (I.L.), RD06/0026/0001 (M.T.) and RD06/0026/0006 (M.C.B.). J.G.Z. was supported by the Programme Alban, scholarship No. E07D400805CO. M.S.G.-G. is a predoctoral fellow of the Ministry of Science and Innovation. M.C.B. was supported by a postdoctoral grant from the Spanish Ministry of Health CD07/00236.Peer Reviewe

Intravenous immunoglobulin promotes antitumor responses by modulating macrophage polarization.

International audienceIntravenous Igs (IVIg) therapy is widely used as an immunomodulatory strategy in inflammatory pathologies and is suggested to promote cancer regression. Because progression of tumors depends on their ability to redirect the polarization state of tumor-associated macrophages (from M1/immunogenic/proinflammatory to M2/anti-inflammatory), we have evaluated whether IVIg limits tumor progression and dissemination through modulation of macrophage polarization. In vitro, IVIg inhibited proinflammatory cytokine production from M1 macrophages and induced a M2-to-M1 polarization switch on human and murine M2 macrophages. In vivo, IVIg modified the polarization of tumor-associated myeloid cells in a Fcεr1γ chain-dependent manner, modulated cytokine blood levels in tumor-bearing animals, and impaired tumor progression via FcγRIII (CD16), FcγRIV, and FcRγ engagement, the latter two effects being macrophage mediated. Therefore, IVIg immunomodulatory activity is dependent on the polarization state of the responding macrophages, and its ability to trigger a M2-to-M1 macrophage polarization switch might be therapeutically useful in cancer, in which proinflammatory or immunogenic functions should be promoted