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

Epilepsy and ring chromosome 20: case report

We present the clinical, electroencephalographic, neuroimaging (brain magnetic resonance image - MRI and spectroscopy by MRI) and cytogenetic findings of a young male patient with a rare cytogenetic anomaly characterised by a de novo 46,XY,r(20)(p13q13.3) karyotype. He presents with mental retardation, emotional liability, and strabismus, without any other significant dysmorphies. There are brain anomalies characterised by corpus callosum, uvula, nodule and cerebellum pyramid hypoplasias, besides arachnoid cysts in the occipital region. He had seizures refractory to pharmacotherapy and long period of confusional status with or without a motor component. The authors recognised that the EEG pattern was not fixed but changed over time, specially for bursts of slow waves with great amplitude accompanied or not by sharp components, and bursts of theta waves sharply contoured. Previously, epilepsy solely has been assigned to region 20q13. However, the important structural cerebral alterations present in our case has not been reported associated to such chromosomal abnormality and may indicate possible new chromosomal sites where such atypical neurological characteristics could be mapped

Polineuropatia no curso do hipertireoidismo: relato de um caso

Os autores apresentam, com apropriada documentação de exames subsidiários, a discussão de caso inusitado de polineuropatia sensitivo-motora, no curso de franco processo hipertireoideano, parecendo mesmo ser coerente denominá-lo de "polineuropatia tireotóxica". A despeito do escasso número de trabalhos a propósito do tema, fortes argumentos são lembrados no sentido de se ligar o processo de hipertireoidismo à progressiva degeneração simultânea, simétrica e distal dos nervos periféricos. Ao final, mostra-se a dificuldade de se reconhecer a etiopatogenia do processo de degeneração dos nervos periféricos, lembrando, porém, a possibilidade de ser de natureza tóxica, carencial ou auto-imune

Rad51-dependent DNA structures accumulate at damaged replication forks in sgs1 mutants defective in the yeast ortholog of BLM RecQ helicase

S-phase cells overcome chromosome lesions through replication-coupled recombination processes that seem to be assisted by recombination-dependent DNA structures and/or replication-related sister chromatid junctions. RecQ helicases, including yeast Sgs1 and human BLM, have been implicated in both replication and recombination and protect genome integrity by preventing unscheduled mitotic recombination events. We have studied the RecQ helicase-mediated mechanisms controlling genome stability by analyzing replication forks encountering a damaged template in sgs1 cells. We show that, in sgs1 mutants, recombination-dependent cruciform structures accumulate at damaged forks. Their accumulation requires Rad51 protein, is counteracted by Srs2 DNA helicase, and does not prevent fork movement. Sgs1, but not Srs2, promotes resolution of these recombination intermediates. A functional Rad53 checkpoint kinase that is known to protect the integrity of the sister chromatid junctions is required for the accumulation of recombination intermediates in sgs1 mutants. Finally, top3 and top3 sgs1 mutants accumulate the same structures as sgs1 cells. We suggest that, in sgs1 cells, the unscheduled accumulation of Rad51-dependent cruciform structures at damaged forks result from defective maturation of recombination-dependent intermediates that originate from the replication-related sister chromatid junctions. Our findings might contribute to explaining some of the recombination defects of BLM cells

"Walter Benjamin, Gershom Scholem e il linguaggio

Walter Benjamin sviluppa nel 1916 una teoria del linguaggio che esporrà nel saggio rimasto inedito Sulla lingua in generale e sulla lingua dell’uomo (1916), e lo farà a stretto contatto, dal 1915, con l’amico Gershom Scholem, allora giovane studente di matematica e filosofia e studioso di ebraismo. Benjamin mostra di essere in piena sintonia con Scholem e con la sua visione cabbalistica del formalismo del linguaggio della Torah, in cui sono fondamentali il suono, il valore numerico e la forma delle lettere, e non i contenuti e i significati del testo, nella sua concezione mediale della lingua dei nomi (riflesso, nel loro caratterizzarsi come idee, della parola creatrice di Dio) e delle parole, che hanno finito per comunicare contenuti estrinseci e sono il fondamento dei concetti. In una serie di note di diario del 1916 Scholem individua un legame – di cui discute con Benjamin – tra una sua “teoria matematica della verità” e la forma interna della lingua ebraica Le conoscenze teologiche di Scholem e le letture che Benjamin e Scholem intraprendono portano entrambi a sviluppare una teoria del linguaggio fondata sulla interpretazione della Genesi e della Cabbalà, ma anche ad affrontare questioni gnoseologiche e matematiche sviluppate a partire da testi kantiani, neokantiani, husserliani e fenomenologici in generale

Innovative design for FAST divertor compatible with remote handling, electromagnetic and mechanical analyses

Divertor is a crucial component in Tokamaks, aiming to exhaust the heat power and particles fluxes com-ing from the plasma during discharges. This paper focuses on the optimization process of FAST divertor,aimed at achieving required thermo-mechanical capabilities and the remote handling (RH) compati-bility. Divertor RH system final layout has been chosen between different concept solutions proposedand analyzed within the principles of Theory of Inventive Problem Solving (TRIZ). The design was aidedby kinematic simulations performed using Digital Mock-Up capabilities of Catia software. Considerableelectromagnetic (EM) analysis efforts and top-down CAD approach enabled the design of a final andconsistent concept, starting from a very first dimensioning for EM loads.In the final version here presented, the divertor cassette supports a set of tungsten (W) actively cooledtiles which compose the inner and outer vertical targets, facing the plasma and exhausting the main partof heat flux. W-tiles are assembled together considering a minimum gap tolerance (0.1–0.5 mm) to bemandatorily respected. Cooling channels have been re-dimensioned to optimize the geometry and thelayout of coolant volume inside the cassette has been modified as well to enhance the general efficiency

Innovative design for FAST divertor compatible with remote handling, electromagnetic and mechanical analyses

Divertor is a crucial component in Tokamaks, aiming to exhaust the heat power and particles fluxes com-ing from the plasma during discharges. This paper focuses on the optimization process of FAST divertor,aimed at achieving required thermo-mechanical capabilities and the remote handling (RH) compati-bility. Divertor RH system final layout has been chosen between different concept solutions proposedand analyzed within the principles of Theory of Inventive Problem Solving (TRIZ). The design was aidedby kinematic simulations performed using Digital Mock-Up capabilities of Catia software. Considerableelectromagnetic (EM) analysis efforts and top-down CAD approach enabled the design of a final andconsistent concept, starting from a very first dimensioning for EM loads.In the final version here presented, the divertor cassette supports a set of tungsten (W) actively cooledtiles which compose the inner and outer vertical targets, facing the plasma and exhausting the main partof heat flux. W-tiles are assembled together considering a minimum gap tolerance (0.1\u20130.5 mm) to bemandatorily respected. Cooling channels have been re-dimensioned to optimize the geometry and thelayout of coolant volume inside the cassette has been modified as well to enhance the general efficiency

Tomografia computadorizada do cranio no diagnostico dos meningiomas: registro de 16 casos

Os autores se referem à importância do emprego da tomografia computadorizada do crânio para o preciso diagnóstico dos meningiomas. Constam da experiência 16 casos, comprovados cirúrgica e histologicamente. A média de idade foi de 52,1 anos, sendo 10 pacientes do sexo feminino e 6 do masculino. Quanto à localização, 5 eram da cavidade orbitrária e/ou asa do esfenóide, 3 parasagitais, 3 da foice, 2 supra-selares, 2 de convexidade e 1 do tentório. Concluem tratar-se de exame de grande positividade (95-98%), praticamente inócuo e que permite, na atualidade, o diagnóstico precoce conduzindo, consequentemente, a melhores resultados terapêuticos