Worldwide prevalence of small ruminant lentiviruses in sheep: A systematic review and meta-analysis

Small Ruminant Lentiviruses (SRLV) are highly prevalent retroviruses with significant genetic diversity and antigenic heterogeneity that cause a progressive wasting disease of sheep called Maedi-visna. This work provides a systematic review and meta-analysis of the last 40 years (1981–2020) of scientific publications on SRLV individual and flock prevalence. Fifty-eight publications and 314 studies were included. Most articles used a single diagnostic test to estimate prevalence (77.6%), whereas articles using three or more tests were scarce (6.9%). Serological tests are more frequently used than direct methods and ELISA has progressively replaced AGID over the last decades. SRLV infection in sheep is widespread across the world, with Europe showing the highest individual prevalence (40.9%) and being the geographical area in which most studies have been performed. Africa, Asia, and North America show values between 16.7% to 21.8% at the individual level. South and Central America show the lowest individual SRLV prevalence (1.7%). There was a strong positive correlation between individual and flock prevalence (¿ = 0.728; p = 0.001). Despite the global importance of small ruminants, the coverage of knowledge on SRLV prevalence is patchy and inconsistent. There is a lack of a gold standard method and a defined sampling strategy among countries and continents

Linking In Vitro Models of Endothelial Dysfunction with Cell Senescence

Disfunció endotelial; Envellliment cel·lularDisfunción endotelial; Envejecimiento celularEndothelial dysfunction; SenescenceEndothelial cell dysfunction is the principal cause of several cardiovascular diseases that are increasing in prevalence, healthcare costs, and mortality. Developing a standardized, representative in vitro model of endothelial cell dysfunction is fundamental to a greater understanding of the pathophysiology, and to aiding the development of novel pharmacological therapies. We subjected human umbilical vein endothelial cells (HUVECs) to different periods of nutrient deprivation or increasing doses of H2O2 to represent starvation or elevated oxidative stress, respectively, to investigate changes in cellular function. Both in vitro cellular models of endothelial cell dysfunction-associated senescence developed in this study, starvation and oxidative stress, were validated by markers of cellular senescence (increase in β-galactosidase activity, and changes in senescence gene markers SIRT1 and P21) and endothelial dysfunction as denoted by reductions in angiogenic and migratory capabilities. HUVECs showed a significant H2O2 concentration-dependent reduction in cell viability (p < 0.0001), and a significant increase in oxidative stress (p < 0.0001). Furthermore, HUVECs subjected to 96 h of starvation, or exposed to concentrations of H2O2 of 400 to 1000 μM resulted in impaired angiogenic and migratory potentials. These models will enable improved physiological studies of endothelial cell dysfunction, and the rapid testing of cellular efficacy and toxicity of future novel therapeutic compounds.This research was funded by Beca de Investigacion Basica en Cardiologia from the Sociedad Española de Cardiologia, Fondo de Investigacion en Salud (grants PI18/00277, PI16/00742, PI19/00264, PI18/00960 and PI15/00553) from the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III–Fondo Europeo de Desarrollo Regional (FEDER), and Spanish Society of Respiratory Medicine (SEPAR) and Catalan Society of Pneumology (SOCAP) grants. FRJT and OTC are the recipients of the Ayudas para la formación de profesorado universitario (FPU19/04925) and Miguel Servet (CP17/00114) grants, respectively, from the Spanish Ministry of Science and Innovation. IDIBAPS belongs to the CERCA Programme, and receives partial funding from the Generalitat de Catalunya. Cofunding was provided by the Fondo Europeo de Desarrollo Regional (FEDER); “Una manera de hacer Europa”

Sirtuin-2, NAD-Dependent Deacetylase, is a new potential therapeutic target for HIV-1 infection and HIV-related neurological dysfunction

The implementation and access to combined antiretroviral treatment (cART) have dramatically improved the quality of life of people living with HIV (PLWH). However, some comorbidities, such as neurological disorders associated with HIV infection still represent a serious clinical challenge. Soluble factors in plasma that are associated with control of HIV replication and neurological dysfunction could serve as early biomarkers and as new therapeutic targets for this comorbidity. We used a customized antibody array for determination of blood plasma factors in 40 untreated PLWH with different levels of viremia and found sirtuin-2 (SIRT2), an NAD-dependent deacetylase, to be strongly associated with elevated viral loads and HIV provirus levels, as well as with markers of neurological damage (a-synuclein [SNCA], brain-derived neurotrophic factor [BDNF], microtubule-associated protein tau [MAPT], and neurofilament light protein [NFL]). Also, longitudinal analysis in HIV-infected individuals with immediate (n = 9) or delayed initiation (n = 10) of cART revealed that after 1 year on cART, SIRT2 plasma levels differed between both groups and correlated inversely with brain orbitofrontal cortex involution. Furthermore, targeting SIRT2 with specific small-molecule inhibitors in in vitro systems using J-LAT A2 and primary glial cells led to diminished HIV replication and virus reactivation from latency. Our data thus identify SIRT2 as a novel biomarker of uncontrolled HIV infection, with potential impact on neurological dysfunction and offers a new therapeutic target for HIV treatment and cure. IMPORTANCE Neurocognitive disorders are frequently reported in people living with HIV (PLWH) even with the introduction of combined antiretroviral treatment (cART). To identify biomarkers and potential therapeutic tools to target HIV infection in peripheral blood and in the central nervous system (CNS), plasma proteomics were applied in untreated chronic HIV-infected individuals with different levels of virus control. High plasma levels of sirtuin-2 (SIRT2), an NAD+ deacetylase, were detected in uncontrolled HIV infection and were strongly associated with plasma viral load and proviral levels. In parallel, SIRT2 levels in the peripheral blood and CNS were associated with markers of neurological damage and brain involution and were more pronounced in individuals who initiated cART later in infection. In vitro infection experiments using specific SIRT2 inhibitors suggest that specific targeting of SIRT2 could offer new therapeutic treatment options for HIV infections and their associated neurological dysfunction

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

A Short Corticosteroid Course Reduces Symptoms and Immunological Alterations Underlying Long-COVID

Despite the growing number of patients with persistent symptoms after acute SARS-CoV-2 infection, the pathophysiology underlying long-COVID is not yet well characterized, and there is no established therapy. We performed a deep immune profiling in nine patients with persistent symptoms (PSP), before and after a 4-day prednisone course, and five post-COVID-19 patients without persistent symptoms (NSP). PSP showed a perturbed distribution of circulating mononuclear cell populations. Symptoms in PSP were accompanied by a pro-inflammatory phenotype characterized by increased conventional dendritic cells and augmented expression of antigen presentation, co-stimulation, migration, and activation markers in monocytes. The adaptive immunity compartment in PSP showed a Th1-predominance, decreased naïve and regulatory T cells, and augmentation of the PD-1 exhaustion marker. These immune alterations reverted after the corticosteroid treatment and were maintained during the 4-month follow-up, and their normalization correlated with clinical amelioration. The current work highlights an immunopathogenic basis together with a possible role for steroids in the treatment for long-COVID

Linking in vitro models of endothelial dysfunction with cell senescence

Endothelial cell dysfunction is the principal cause of several cardiovascular diseases that are increasing in prevalence, healthcare costs, and mortality. Developing a standardized, representative in vitro model of endothelial cell dysfunction is fundamental to a greater understanding of the pathophysiology, and to aiding the development of novel pharmacological therapies. We subjected human umbilical vein endothelial cells (HUVECs) to different periods of nutrient deprivation or increasing doses of H2O2 to represent starvation or elevated oxidative stress, respectively, to investigate changes in cellular function. Both in vitro cellular models of endothelial cell dysfunction‐associated senescence developed in this study, starvation and oxidative stress, were validated by markers of cellular senescence (increase in β‐galactosidase activity, and changes in senescence gene markers SIRT1 and P21) and endothelial dysfunction as denoted by reductions in angiogenic and migratory capabilities. HUVECs showed a significant H2O2 concentration-dependent reduction in cell viability (p<0.0001), and a significant increase in oxidative stress (p<0.0001). Furthermore, HUVECs subjected to 96h of starvation, or exposed to concentrations of H2O2 of 400 to 1000μM resulted in impaired angiogenic and migratory potentials. These models will enable improved physiological studies of endothelial cell dysfunction, and the rapid testing of cellular efficacy and toxicity of future novel therapeutic compounds

CO2 y cambio climático: libro de la exposición temática itinerante

[102] p. : il. col. ; 30 cm[ES] Las concentraciones atmosféricas de gases de efecto invernadero (GEI) no han dejado de aumentar desde la época preindustrial debido a las actividades humanas. La unanimidad de los científicos a la hora de interpretar las observaciones y evidencias que se están produciendo en la Tierra por este efecto es cada vez mayor, los estudios climáticos ponen de manifiesto la relación entre el cambio climático y el aumento de concentraciones de GEI. La labor de los científicos en facilitar el acceso a información relevante en materia de cambio climático contribuye notablemente a incrementar la sensibilización y la concienciación de la sociedad frente a los problemas ambientales. Un grupo de científicos del INCAR ha puesto en marcha una interesante iniciativa para acercar el conocimiento sobre el cambio climático al público, a través de una exposición itinerante que está recorriendo diversos espacios de uso público cotidiano, como son las grandes superficies comerciales. Los contenidos de esta muestra gráfica se presentan ahora en este libro acompañados de explicaciones que ayudan a la comprensión del riesgo que el calentamiento global representa para los sistemas naturales y socioeconómicos y de la importancia de las actuaciones de mitigación y adaptación frente al cambio climático. Se trata de un intento de llegar al ciudadano con un mensaje claro sobre las causas y efectos que producen los comportamientos poco sostenibles de nuestra sociedad sobre el medio ambiente y la importancia de dar una respuesta desde lo individual con un cambio en nuestros patrones de consumo, fomentando hábitos responsables, como el ahorro de energía, la utilización del transporte público, el uso responsable de recursos como el agua o la gestión adecuada de los residuos en nuestras viviendas. El papel que la educación y la sensibilización tienen para moldear actitudes, valores y conductas, facilita que las personas y los colectivos advirtamos la necesidad de cambiar nuestro estilo de vida para que éste sea compatible con la renovación natural de los recursos y con la conservación de los ecosistemas naturales y, en definitiva, con el desarrollo sostenible.Nuestro agradecimiento a los organismos regionales del Principado de Asturias, la Oficina para la Sostenibilidad, el Cambio Climático y la Participación (OSCCP) y la Fundación para el Fomento en Asturias de la Investigación Científica Aplicada y la Tecnología (FICYT), así como a la Fundación Española para la Ciencia y la Tecnología (FECYT) por su apoyo económico en la edición de este libro. Asimismo, agradecemos a Cajastur la financiación de los paneles de la exposición “CO2 y Cambio Climático”. Este libro es fruto de las colaboraciones de investigadores del Instituto Nacional del Carbón de Oviedo (INCAR-CSIC), del Institut Mediterrani d'Estudis Avançats de Esporles - Mallorca (IMEDEA, CSIC-UIB), del Instituto Geológico y Minero de España (IGME), del Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT) y del Consejo de Seguridad Nuclear (CSN). Los textos que acompañan a los paneles ilustrativos han sido cuidadosamente corregidos por los Doctores Carlos Abanades, Ángeles Gómez y Ana Arenillas, todos ellos del Instituto Nacional del Carbón (INCAR-CSIC). El listado completo de autores y participantes se encuentra al final del libro.Peer reviewe