Low dose anti-inflammatory radiotherapy for the treatment of pneumonia by covid-19 : A proposal for a multi-centric prospective trial

COVID-19 is a highly contagious viral infection with high morbidity that is draining health resources. The biggest complication is pneumonia, which has a serious inflammatory component, with no standardized treatment. Low-dose radiation therapy (LD-RT) is non-invasive and has anti-inflammatory effects that can interfere with the inflammatory cascade, thus reducing the severity of associated cytokine release and might be useful in the treatment of respiratory complications caused by COVID-19. This multicentric prospective clinical trial seeks to evaluate the efficacy of bilateral lung LD-RT therapy as a treatment for interstitial pneumonia in patients with COVID-19 for improving respiratory function. This prospective study will have 2 phases: I) an exploratory phase enrolling 10 patients, which will assess the feasibility and efficacy of low-dose lung irradiation, evaluated according to an increase in the PaO2/FiO2 ratio of at least 20% at 48-72 h with respect to the pre-irradiation value. If a minimum efficiency of 30% of the patients is not achieved, the study will not be continued. II) Non-randomized comparative phase in two groups: a control group, which will only receive pharmacological treatment, and an experimental arm with pharmacological treatment and LD-RT. It will include 96 patients, the allocation will be 1: 2, that is, 32 in the control arm and 64 in the experimental arm. The primary end-point will be the efficacy of LD-RT in patients with COVID-19 pneumonia according to an improvement in PaO2/FiO2. Secondary objectives will include the safety of bilateral lung LD-RT, an improvement in the radiology image, overall mortality rates at 15 and 30 days after irradiation and characterizing anti-inflammatory mechanisms of LD-RT by measuring the level of expression of adhesion molecules, anti-inflammatory cytokines and oxidative stress mediators. Trial registration: ClinicalTrial.gov NCT-04380818

Unraveling a Neanderthal palimpsest from a zooarcheological and taphonomic perspective

Practically all archeological assemblages are palimpsests. In spite of the high temporal resolution of Abric Romaní site, level O, dated to around 55 ka, is not an exception. This paper focuses on a zooarcheological and taphonomic analysis of this level, paying special attention to spatial and temporal approaches. The main goal is to unravel the palimpsest at the finest possible level by using different methods and techniques, such as archeostratigraphy, anatomical and taxonomical identification, taphonomic analysis, faunal refits and tooth wear analysis. The results obtained are compared to ethnoarcheological data so as to interpret site structure. In addition, activities carried out over different time spans (from individual episodes to long-term behaviors) are detected, and their spatial extent is explored, allowing to do inferences on settlement dynamics. This leads us to discuss the temporal and spatial scales over which Neanderthals carried out different activities within the site, and how they can be studied through the archeological record

Characterization, high-resolution mapping and differential expression of three homologous PAL genes in Coffea canephora Pierre (Rubiaceae)

Phenylalanine ammonia lyase (PAL) is the first entry enzyme of the phenylpropanoid pathway producing phenolics, widespread constituents of plant foods and beverages, including chlorogenic acids, polyphenols found at remarkably high levels in the coffee bean and long recognized as powerful antioxidants. To date, whereas PAL is generally encoded by a small gene family, only one gene has been characterized in Coffea canephora (CcPAL1), an economically important species of cultivated coffee. In this study, a molecular- and bioinformatic-based search for CcPAL1 paralogues resulted successfully in identifying two additional genes, CcPAL2 and CcPAL3, presenting similar genomic structures and encoding proteins with close sequences. Genetic mapping helped position each gene in three different coffee linkage groups, CcPAL2 in particular, located in a coffee genome linkage group (F) which is syntenic to a region of Tomato Chromosome 9 containing a PAL gene. These results, combined with a phylogenetic study, strongly suggest that CcPAL2 may be the ancestral gene of C. canephora. A quantitative gene expression analysis was also conducted in coffee tissues, showing that all genes are transcriptionally active, but they present distinct expression levels and patterns. We discovered that CcPAL2 transcripts appeared predominantly in flower, fruit pericarp and vegetative/lignifying tissues like roots and branches, whereas CcPAL1 and CcPAL3 were highly expressed in immature fruit. This is the first comprehensive study dedicated to PAL gene family characterization in coffee, allowing us to advance functional studies which are indispensable to learning to decipher what role this family plays in channeling the metabolism of coffee phenylpropanoids

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

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

Using biased molecular dynamics and Brownian dynamics in the study of fluorescent proteins

cited By 7International audienceThe present article presents a theoretical study of the dynamics of the chromophore of the Green Fluorescent Protein in its excited state on a long time scale (a few ten nanoseconds) in order to help the interpretation of time resolved experiments. The starting hypothesis is that the quenching of fluorescence is related to the internal motion of the chromophore, usually called 'φ torsion'. In fact, that motion is hindered by the protein and cannot be studied by standard molecular dynamics. Therefore we have developed a different approach involving three steps. First the potential of mean force (PMF) along the considered torsion is obtained by biased molecular dynamics (umbrella sampling). Then, a long time scale, single particle Brownian dynamics is performed using that PMF and an appropriate diffusion constant. Finally we determine the nth passage time (NPT) distribution functions at geometries or regions where nonradiative ground state recovery may occur. The NPT distributions generalize the more usual 'mean first passage time' and allow determining different quantities like fluorescence decay profiles, mean fluorescence lifetime, quantum yield etc. These quantities are used here in a qualitative discussion of the fluorescence decay in Green Fluorescent Protein

Relation between pH, structure, and absorption spectrum of Cerulean: A study by molecular dynamics and TD DFT calculations

cited By 6International audienceMolecular dynamics (MD) and quantum mechanical calculations of the Cerulean green fluorescent protein (a variant of enhanced cyan fluorescent protein ECFP) at pH 5.0 and 8.0 are presented, addressing two questions arising from experimental results (Malo et al., Biochemistry 2007;46:9865 - 9873): the origin of the blue shift of absorption spectrum when the pH is decreased from 8.0 to 5.0, and the lateral chain orientation of the key residue Asp 148. We demonstrate that the blue shift is reproduced assuming that a rotation around the single bond of the exocydie ring of the chromophore takes place when the pH changes from 5.0 to 8.0. We find that Asp 148 is protonated and inside the barrel at pH 5.0 in agreement with crystallographic data. However, the hydrogen bond pattern of Asp 148 is different in simulations of the solvated protein and in the crystal structure. This difference is explained by a partial closing of the cleft between strands 6 and 7 in MD simulations. This study provides also a structure at pH 8.0: the Asp 148 carboxylate group is exposed to the solvent and the chromophore is stabilized in the trans conformation by a tighter hydrogen bond network. This work gives some insight into the relationship between the pH and the chromophore conformation and suggests an interpretation of the very similar fluorescent properties of ECFP and ECFP/ H148D