A parallel-group, multicenter randomized, double-blinded, placebo-controlled, phase 2/3, clinical trial to test the efficacy of pyridostigmine bromide at low doses to reduce mortality or invasive mechanical ventilation in adults with severe SARS-CoV-2 infection: the Pyridostigmine In Severe COvid-19 (PISCO) trial protocol

© 2020, The Author(s). Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the causative agent of coronavirus disease 2019 (COVID-19), may lead to severe systemic inflammatory response, pulmonary damage, and even acute respiratory distress syndrome (ARDS). This in turn may result in respiratory failure and in death. Experimentally, acetylcholine (ACh) modulates the acute inflammatory response, a neuro-immune mechanism known as the inflammatory reflex. Recent clinical evidence suggest that electrical and chemical stimulation of the inflammatory reflex may reduce the burden of inflammation in chronic inflammatory diseases. Pyridostigmine (PDG), an ACh-esterase inhibitor (i-ACh-e), increases the half-life of endogenous ACh, therefore mimicking the inflammatory reflex. This clinical trial is aimed at evaluating if add-on of PDG leads to a decrease of invasive mechanical ventilation and death among patients with severe COVID-19. Methods: A parallel-group, multicenter, randomized, double-blinded, placebo-controlled, phase 2/3 clinical trial to test the efficacy of pyridostigmine bromide 60 mg/day P.O. to reduce the need for invasive mechanical ventilation and mortality in hospitalized patients with severe COVID-19. Discussion: This study will provide preliminary evidence of whether or not -by decreasing systemic inflammation- add-on PDG can improve clinical outcomes in patients with severe COVID-19. Trial registration: ClinicalTrials.gov NCT04343963 (registered on April 14, 2020)

Options for agriculture at Marrakech climate talks: messages for SBSTA 45 agriculture negotiators

SBSTA 45 in Marrakech represents a unique opportunity for Parties to decide on the future of agriculture within the UNFCCC. The process of discussions on issues related to agriculture initiated at COP17 in Durban 2011 culminates at COP22 in Marrakech 2016. The explicit reference to food security in the preamble of the Paris Agreement and the Intended Nationally Determined Contributions which prioritize agriculture as a sector for adaptation and mitigation actions, provide a foundation for Parties to develop appropriate frameworks to support actions within the agricultural sector. SBSTA workshops on agriculture in 2015 and 2016 allowed Parties to share experiences, identify priorities, and propose ways of taking action within the agricultural sector and so provide the core knowledge base to work from. As Parties reach a decision on issues related to agriculture at SBSTA 45, a number of options are available. This report presents ten such options that might contribute to a decision, taking into consideration political priorities, implementation arrangements, timelines and level of ambition. Options outlined in this report are not mutually exclusive and can be combined in many different ways

Treballs d'investigació en atenció primària: revisió dels treballs en llengües espanyoles publicats l'any 1986

Revisem 29 treballs elaborats per professionals d'atenció primària i publicats a: Atención Primaria, Medicina Clínica, Gaseta Sanitaria, Revista Clínica Española, Revista Española de Pediatría i Annals de Medicina. La majoria els trobem realitzats per especialistes o residents de Medicina Familiar i Comunitària, amb absència de pediatres. Entre els temes analitzats destaca l'anàlisi de la demanda, hipertensió arterial i vacunacions, que totalitzen quasi el 50% dels treballs. Cal ressaltar un 89% de dissenys descriptius, amb solament dos de tipus analític o experimental. Sobre 6 paràmetres d'adequació metodològica hi hagué un compliment mitjà de 4,38 (DE = 2,23). El 52% dels treballs no tenien tractament estadístic. Creiem que hi ha una extensa variabilitat en la qualitat deis treballs i que és necessari adaptar la temàtica d'interès deis investigadors i adaptar els dissenys a la demostració d'hipòtesis que suposin canvis en la pràctica assistencial

Protease-driven lysosomal activity is a core mechanism for macrophage driven collagen remodeling during liver and kidney fibrosis

Trabajo presentado en el 2nd International Workshop on Liver and Gut Fibrosis, celebrado en Valencia (España), los días 26 y 27 de octubre de 202

Autophagy modulates endothelial junctions to restrain neutrophil diapedesis during inflammation

The migration of neutrophils from the blood circulation to sites of infection or injury is a key immune response and requires the breaching of endothelial cells (ECs) that line the inner aspect of blood vessels. Unregulated neutrophil transendothelial cell migration (TEM) is pathogenic, but the molecular basis of its physiological termination remains unknown. Here, we demonstrated that ECs of venules in inflamed tissues exhibited a robust autophagic response that was aligned temporally with the peak of neutrophil trafficking and was strictly localized to EC contacts. Genetic ablation of EC autophagy led to excessive neutrophil TEM and uncontrolled leukocyte migration in murine inflammatory models, while pharmacological induction of autophagy suppressed neutrophil infiltration into tissues. Mechanistically, autophagy regulated the remodeling of EC junctions and expression of key EC adhesion molecules, facilitating their intracellular trafficking and degradation. Collectively, we have identified autophagy as a modulator of EC leukocyte trafficking machinery aimed at terminating physiological inflammation

In vivo partial cellular reprogramming enhances liver plasticity and regeneration.

Mammals have limited regenerative capacity, whereas some vertebrates, like fish and salamanders, are able to regenerate their organs efficiently. The regeneration in these species depends on cell dedifferentiation followed by proliferation. We generate a mouse model that enables the inducible expression of the four Yamanaka factors (Oct-3/4, Sox2, Klf4, and c-Myc, or 4F) specifically in hepatocytes. Transient in vivo 4F expression induces partial reprogramming of adult hepatocytes to a progenitor state and concomitantly increases cell proliferation. This is indicated by reduced expression of differentiated hepatic-lineage markers, an increase in markers of proliferation and chromatin modifiers, global changes in DNA accessibility, and an acquisition of liver stem and progenitor cell markers. Functionally, short-term expression of 4F enhances liver regenerative capacity through topoisomerase2-mediated partial reprogramming. Our results reveal that liver-specific 4F expression in vivo induces cellular plasticity and counteracts liver failure, suggesting that partial reprogramming may represent an avenue for enhancing tissue regeneration

Open access solutions for biodiversity journals : Do not replace one problem with another

Peer reviewe

Oil and Gas Projects in the Western Amazon: Threats to Wilderness, Biodiversity, and Indigenous Peoples

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.The western Amazon is the most biologically rich part of the Amazon basin and is home to a great diversity of indigenous ethnic groups, including some of the world’s last uncontacted peoples living in voluntary isolation. Unlike the eastern Brazilian Amazon, it is still a largely intact ecosystem. Underlying this landscape are large reserves of oil and gas, many yet untapped. The growing global demand is leading to unprecedented exploration and development in the region. Without improved policies, the increasing scope and magnitude of planned extraction means that environmental and social impacts are likely to intensify. We review the most pressing oil- and gas-related conservation policy issues confronting the region. These include the need for regional Strategic Environmental Impact Assessments and the adoption of roadless extraction techniques. We also consider the conflicts where the blocks overlap indigenous peoples’ territories

Promoción de la salud y entornos saludables

A forestar forestalAplicación de un programa educativo participativo en salud  bucal a una comunidad de adultos mayoresBiblioteca móvil y su implementación en el hospital Padre HurtadoConsumo de riesgo de alcohol en Chile: una propuesta innovadora de intervenciónDiseño de un programa interactivo de promoción de la salud vocal para NB1Encuentro formativo en promoción de salud y gestión de entornos saludables para TenoExperiencia docente: programa intersectorial de promoción/prevención en preescolares de comunas vulnerables, Región MetropolitanaFiltrado glomerular, método preventivo aparición de fibrosis sistémica nefrogénica por gadolinio en examen de RMImplementación de consejerías en vida sana en APS, Región de los RíosMedicina preventiva en feria libre de la población San Gregorio: Cecof San Gregorio, Contagiando SaludMetodología innovadora en la enseñanza de una ectoparasitosisPrevención de accidentes por monóxido de carbono en edificios, Providencia 2002-2009Programa de promoción y prevención en salud bucal para preescolaresPromoviendo hábitos saludables en los vecinos de Reñaca Alto, Viña del Mar, 2009Rol de la capacitación en la implementación de acciones para la prevención de la obesidadSatisfacción usuaria en el Cesfam Natales a un año de su funcionamientoTres estrategias publicitarias y de comunicación aplicadas al consumo de alcohol de bajo riesgoTropa de la salud: uso de los medios como forma de promover la salu

NEXT-CRAB-0: A High Pressure Gaseous Xenon Time Projection Chamber with a Direct VUV Camera Based Readout

The search for neutrinoless double beta decay ($0\nu\beta\beta$) remains one of the most compelling experimental avenues for the discovery in the neutrino sector. Electroluminescent gas-phase time projection chambers are well suited to $0\nu\beta\beta$ searches due to their intrinsically precise energy resolution and topological event identification capabilities. Scalability to ton- and multi-ton masses requires readout of large-area electroluminescent regions with fine spatial resolution, low radiogenic backgrounds, and a scalable data acquisition system. This paper presents a detector prototype that records event topology in an electroluminescent xenon gas TPC via VUV image-intensified cameras. This enables an extendable readout of large tracking planes with commercial devices that reside almost entirely outside of the active medium.Following further development in intermediate scale demonstrators, this technique may represent a novel and enlargeable method for topological event imaging in $0\nu\beta\beta$.Comment: 32 Pages, 22 figure