Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Elaboración y aplicación de unidades didácticas en el aula desde una perspectiva globalizada

El gran objetivo de este proyecto consistió en la elaboración de una unidad didáctica, teniendo en cuenta las recomendaciones de la LOGSE, tanto desde una perspectiva metodológica como de los criterios de evaluación. También, adaptar temas transversales que tuvieran un carácter globalizador. Dicho objetivo se consiguió en su totalidad, se elaboró la unidad didáctica propuesta: 'Van a venir los reyes' para el primer ciclo de la Educación primaria; participan 6 Centros de EGB todos pertenecientes a la zona de Puerto del Rosario en Fuerteventura. La experiencia resultó ser positiva a nivel de comunicación de grupo, de implicación en el trabajo y de resultados del mismo. Se propone continuar con el proyecto el curso siguiente (94-95) y elaborar los materiales curriculares necesarios.Gobierno de Canarias. Dirección General de Ordenación e Innovación EducativaCanariasES

Síndrome pulmonar por hantavirus en la provincia de Tucumán asociado a un genotipo viral inesperado

Fil: Ciancaglini, Matías. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Virología. Servicio de Biología Molecular; Argentina.Fil: Bellomo, Carla M. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Virología. Servicio de Biología Molecular; Argentina.Fil: Torres Cabreros, Clara L. Hospital Italiano de Buenos Aires; Argentina.Fil: Alonso, Daniel. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Virología. Servicio de Biología Molecular; Argentina.Fil: Bassi, Sabrina C. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Virología. Servicio de Biología Molecular; Argentina.Fil: Iglesias, Ayelén A. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Virología. Servicio de Biología Molecular; Argentina.Fil: Martínez, Valeria P. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Virología. Servicio de Biología Molecular; Argentina.We describe the characterization of the viral genotype involved in the first case of hantavirus pulmonary syndrome reported in Tucumán, a Northwestern province of Argentina. A 23-year-old woman, with no record of travel history and previously diagnosed with an antiphospholipid syndrome, died after 11 days of severe cardiopulmonary insufficiency. Among the four endemic regions of hantavirus pulmonary syndrome in Argentina, the Northwest Region has the highest incidence, exceeding 50% of all reported cases in the country. Until now, only Salta and Jujuy (2 out of the 6 provinces composing the Northwest Region), reported cases of hantavirus pulmonary syndrome, all of which occurred in the Yungas Forest area. Remarkably, the viral genotype characterized in this case showed higher nucleotide identity with the Andes-BsAs genotype most prevalent in Buenos Aires province, located 1400 km apart from Tucumán, than with any of the commonly found genotypes in the Northwest Region. The Andes-BsAs genotype has been associated with 30% lethality and interhuman transmission in Buenos Aires province. Interhuman transmission cannot be ruled out in the present case

Síndrome pulmonar por hantavirus en la provincia de Tucumán asociado a un genotipo viral inesperado

Fil: Ciancaglini, Matías. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Virología. Servicio de Biología Molecular; Argentina.Fil: Bellomo, Carla M. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Virología. Servicio de Biología Molecular; Argentina.Fil: Torres Cabreros, Clara L. Hospital Italiano de Buenos Aires; Argentina.Fil: Alonso, Daniel. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Virología. Servicio de Biología Molecular; Argentina.Fil: Bassi, Sabrina C. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Virología. Servicio de Biología Molecular; Argentina.Fil: Iglesias, Ayelén A. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Virología. Servicio de Biología Molecular; Argentina.Fil: Martínez, Valeria P. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Departamento de Virología. Servicio de Biología Molecular; Argentina.We describe the characterization of the viral genotype involved in the first case of hantavirus pulmonary syndrome reported in Tucumán, a Northwestern province of Argentina. A 23-year-old woman, with no record of travel history and previously diagnosed with an antiphospholipid syndrome, died after 11 days of severe cardiopulmonary insufficiency. Among the four endemic regions of hantavirus pulmonary syndrome in Argentina, the Northwest Region has the highest incidence, exceeding 50% of all reported cases in the country. Until now, only Salta and Jujuy (2 out of the 6 provinces composing the Northwest Region), reported cases of hantavirus pulmonary syndrome, all of which occurred in the Yungas Forest area. Remarkably, the viral genotype characterized in this case showed higher nucleotide identity with the Andes-BsAs genotype most prevalent in Buenos Aires province, located 1400 km apart from Tucumán, than with any of the commonly found genotypes in the Northwest Region. The Andes-BsAs genotype has been associated with 30% lethality and interhuman transmission in Buenos Aires province. Interhuman transmission cannot be ruled out in the present case

BOPHYs versus BODIPYs: A comparison of their performance as effective multi-function organic dyes

11 pags., 8 figs., 2tabs., 1 app.The computationally-aided photophysical and lasing properties of a selected battery of BOPHYs are described and compared to those of related BODIPY counterparts. The present joined theoretical-experimental study helps to put into context the weaknesses and strengths of both dye families under different irradiation conditions. The chemical versatility of the BOPHY scaffold has been also comparatively explored to modulate key photonic properties towards the development of red-emitting dyes, chiroptical dyes and singlet oxygen photosensitizers. Thus, BOPHY BINOLation by fluorine substitution with enantiopure BINOLs endows the BOPHY chromophore with chiroptical activity, as supporting by the simulated circular dichroism, decreasing deeply its fluorescent response due to the promotion of fluorescence-quenching intramolecular charge transfer (ICT). Interestingly, the sole alkylation of the BOPHY core strongly modulates the promotion of ICT, allowing the generation of highly bright BINOL-based BOPHY dyes. Moreover, 3,3′-dibromoBINOLating BOPHYs can easily achieve singlet-oxygen photogeneration, owing to spin-orbit coupling mediated by heavy-atom effect feasible in view of the theoretically predicted disposition of the bromines surrounding the chromophore. From this background, we have established the master guidelines to design bright fluorophores and laser dyes, photosensitizers for singlet oxygen production and chiroptical dyes based on BOPHYs. The possibility to finely mix and balance such properties in a given molecular scaffold outstands BOPHYs as promising dyes competing with the well-settled BODIPY dyes.Financial support from MINECO (MAT2017-83856-C3-1-P, -2-P and-3-P) and Gobierno Vasco (IT912-16) is gratefully acknowledged. G.M.thanks the NIH, Minority Biomedical Research Support (1 SC3GM089589-08), and the Henry Dreyfus Teacher-Scholar Award forfi-nancial support. E.A.Z. and R.S.L. thank Gobierno Vasco for a pre-doctoral fellowship and a postdoctoral contract, respectively. J.J.thanks Comunidad de Madrid/UCM for a research contract

Advanced wastewater treatment and membrane fouling control by electro-encapsulated self-forming dynamic membrane bioreactor

An advanced concept of aerobic membrane bioreactors (MBRs) for highly efficient wastewater treatment has been disclosed by introduction of an electro and encapsulated self-forming dynamic biomembrane (e-ESFDM). The biological filtering membrane is intercalated between two woven polyester fabrics as supports that assist the formation and protect the biomembrane. The innovative architecture of the e-ESFDM in combination with electrocoagulation processes resulted in efficient and cost-effective wastewater treatment and control of the membrane fouling. The performance of the e-ESFDMBR was compared to a yet highly efficient ESFDMBR, where the electric field was not present. The ESFDM-based reactors both showed comparable results in the removal of organic matter, in terms of COD and DOC. On the other hand, e-ESFDMBR exceeded the performance of the ESFDMBR in the reduction of nitrogen- and phosphorous-containing pollutants, responsible for eutrophication processes in the environment, and recalcitrant molecules, such as humic-like substances. In addition, an extremely low fouling rate was observed for the e-ESFDM bioreactor. Insights on the biological processes involved in the developed MBR were provided by investigations on the microbiological diversity found in reactor mixed liquor, ESFDM layer and treated wastewater

The differing effects of a dual acting regulator on SIRT1

SIRT1 is an NAD+-dependent protein deacetylase that has been shown to play a significant role in many biological pathways, such as insulin secretion, tumor formation, lipid metabolism, and neurodegeneration. There is great interest in understanding the regulation of SIRT1 to better understand SIRT1-related diseases and to better design therapeutic approaches that target SIRT1. There are many known protein and small molecule activators and inhibitors of SIRT1. One well-studied SIRT1 regulator, resveratrol, has historically been regarded as a SIRT1 activator, however, recent studies have shown that it can also act as an inhibitor depending on the identity of the peptide substrate. The inhibitory nature of resveratrol has yet to be studied in detail. Understanding the mechanism behind this dual behavior is crucial for assessing the potential side effects of STAC-based therapeutics. Here, we investigate the detailed mechanism of substrate-dependent SIRT1 regulation by resveratrol. We demonstrate that resveratrol alters the substrate recognition of SIRT1 by affecting the K M values without significantly impacting the catalytic rate (k cat). Furthermore, resveratrol destabilizes SIRT1 and extends its conformation, but the conformational changes differ between the activation and inhibition scenarios. We propose that resveratrol renders SIRT1 more flexible in the activation scenario, leading to increased activity, while in the inhibition scenario, it unravels the SIRT1 structure, compromising substrate recognition. Our findings highlight the importance of substrate identity in resveratrol-mediated SIRT1 regulation and provide insights into the allosteric control of SIRT1. This knowledge can guide the development of targeted therapeutics for diseases associated with dysregulated SIRT1 activity