Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

As vicissitudes da formação docente em serviço: a proposta reflexiva em debate The in-service teacher education: the reflective proposal in debate

Este artigo tem por objetivo apresentar algumas das conclusões de uma investigação realizada junto a professores da Rede Municipal de Ensino de São Paulo que participam de grupos de formação em serviço, a fim de conferir visibilidade aos efeitos que a prática formativa concreta vem produzindo na profissionalidade docente. Destaca, em particular, as vicissitudes ocasionadas nesse grupo quando experienciam uma modalidade formativa contemporânea, pautada no modelo de formação reflexiva. As idéias desenvolvidas no artigo inscrevem-se no campo conceitual da psicologia institucional. A partir desse enquadramento teórico, o texto trabalha com o pressuposto de que os recentes paradigmas de formação docente em serviço, ao serem operados por práticas formativas concretas, promovem novas possibilidades de experiência de si para os professores, conferindo novas figurações de subjetividade para os professores no tempo presente - professor-reflexivo, professor-autônomo, professor-investigativo. No interior de relações institucionalizadas, a vivência destas figurações é metabolizada pelos docentes, que produzem uma forma peculiar de reflexão, não vislumbrada na pauta dos programas de formação. Instalados nas práticas concretas de formação em serviço, os professores produzem um tipo de reflexão particular que escapa dos objetos definidos no design formativo e do contorno reflexivo mapeado a priori. A reflexão tangível nas falas docentes narra o confronto desse protagonista com seu lugar instituído na profissão, problematizando o "dever ser" de seu ofício nos dias de hoje.<br>This article presents some of the findings of a study conducted with teachers from the public school system of São Paulo (capital), which take part in in-service teacher education groups. The purpose is to give visibility to the effects that the concrete formative practice has been producing upon teacher’s professionality. The article highlights in particular the vicissitudes experienced by the group when exposed to a contemporary modality of teacher education based on the model of reflective education. The ideas developed here belong to the conceptual framework of Institutional Psychology. From this theoretical framework, the text deals with the assumption that the recent paradigms in teacher education, when worked through concrete formative practices, promote new possibilities of self-experience to the teachers, endowing them at the present time with new images of subjectivity - reflective teacher, autonomous teacher, research teacher. Within institutionalized relations, the experience of those images is metabolized by the teachers, who produce a peculiar form of reflection not envisaged in the agenda of teacher education programs. Teachers, entered in concrete practices of in-service education, produce a particular kind of reflection that escapes from the objects defined in the formative design and from the reflective borders traced a priori. The tangible reflection in the teacher’s speeches tells of the clash between this agent and her attributed professional place, problematizing the "must be" of his craft nowadays

Reorganization and Conformational Changes in the Reduction of Tetraheme Cytochromes

Molecular dynamics simulation (MD) constitutes an alternative to time-consuming experiments for studying conformational changes. We apply MD on a redox system where experimental information exists for the fully oxidized and fully reduced states: tetraheme cytochrome c(3). Instead of doing one simulation for each state, we apply 10 4-ns replicas for both states, which provides robust statistics to characterize the redox changes. Besides these long simulations, we perform 120 short ones (50 ps), where an equilibrated oxidized state is perturbed to a reduced state. This allows the application of a nonequilibrium method, the subtraction technique, which makes it possible to characterize the different timescales of conformational changes. Reduction induces conformational changes in the N-terminus and on the loops spanning residues 36–42 and 88–93, which correlate very well with experiments, demonstrating the applicability of this methodology. We also analyze the effect of reduction on hydrogen bonds, solvent accessible surface and bound water, the changes being found to involve the hemes and propionate groups. Redox-induced protonation is also investigated, by protonating the propionates D from hemes I and IV. Although this change in the former does not have major conformational consequences, it induces in the latter conformational changes beyond the ones obtained with reduction

NMR structure of the haem core of a novel tetrahaem cytochrome isolated from Shewanella frigidimarina: identification of the haem-specific axial ligands and order of oxidation

The tetrahaem cytochrome isolated during anaerobic growth of Shewanella frigidimarina NCIMB400 is a small protein (86 residues) involved in electron transfer to Fe(III), which can be used as a terminal respiratory oxidant by this bacterium. A 3D solution structure model of the reduced form of the cytochrome has been determined using NMR data in order to determine the relative orientation of the haems. The haem core architecture of S. frigidimarina tetrahaem cytochrome differs from that found in all small tetrahaem cytochromes c(3) so far isolated from strict anaerobes, but has some similarity to the N-terminal cytochrome domain of flavocytochrome c(3) isolated from the same bacterium. NMR signals obtained for the four haems of S. frigidimarina tetrahaem cytochrome at all stages of oxidation were cross-assigned to the solution structure using the complete network of chemical exchange connectivities. Thus, the order in which each haem in the structure becomes oxidised was determined

Thermodynamic and kinetic characterisation of individual haems in multicentre cytochromes c(3)

The characterisation of individual centres in multihaem proteins is difficult due to the similarities in the redox and spectroscopic properties of the centres. NMR has been used successfully to distinguish redox centres and allow the determination of the microscopic thermodynamic parameters in several multihaem cytochromes c3 isolated from different sulphate-reducing bacteria. In this article we show that it is also possible to discriminate the kinetic properties of individual centres in multihaem proteins, if the complete microscopic thermodynamic characterisation is available and the system displays fast intramolecular equilibration in the time scale of the kinetic experiment. The deconvolution of the kinetic traces using a model of thermodynamic control provides a reference rate constant for each haem that does not depend on driving force and can be related to structural factors. The thermodynamic characterisation of three tetrahaem cytochromes and their kinetics of reduction by sodium dithionite are reported in this paper. Thermodynamic and kinetic data were fitted simultaneously to a model to obtain microscopic reduction potentials, haem–haem and haem–proton interacting potentials, and reference rate constants for the haems. The kinetic information obtained for these cytochromes and recently published data for other multihaem cytochromes is discussed with respect to the structural factors that determine the reference rates. The accessibility for the reducing agent seems to play an important role in controlling the kinetic rates, although is clearly not the only factor

Proton-assisted two-electron transfer in natural variants of tetraheme cytochromes from Desulfomicrobium Sp

The tetraheme cytochrome c(3) isolated from Desulfomicrobium baculatum (DSM 1743) (Dsmb) was cloned, and the sequence analysis showed that this cytochrome differs in just three amino acid residues from the cytochrome c(3) isolated from Desulfomicrobium norvegicum (Dsmn): (DsmnXXDsmb) Thr-37 --&gt; Ser, Val-45 --&gt; Ala, and Phe-88 --&gt; Tyr. X-ray crystallography was used to determine the structure of cytochrome c(3) from Dsmb, showing that it is very similar to the published structure of cytochrome c(3) from Dsmn. A detailed thermodynamic and kinetic characterization of these two tetraheme cytochromes c(3) was performed by using NMR and visible spectroscopy. The results obtained show that the network of cooperativities between the redox and protonic centers is consistent with a synergetic process to stimulate the hydrogen uptake activity of hydrogenase. This is achieved by increasing the affinity of the cytochrome for protons through binding electrons and, reciprocally, by favoring a concerted two-electron transfer assisted by the binding of proton(s). The data were analyzed within the framework of the differences in the primary and tertiary structures of the two proteins, showing that residue 88, close to heme I, is the main cause for the differences in the microscopic thermodynamic parameters obtained for these two cytochromes c(3). This comparison reveals how replacement of a single amino acid can tune the functional properties of energy-transducing proteins, so that they can be optimized to suit the bioenergetic constraints of specific habitats