Staphylococcus aureus infective endocarditis versus bacteremia strains: Subtle genetic differences at stake

AbstractInfective endocarditis (IE)(1) is a severe condition complicating 10–25% of Staphylococcus aureus bacteremia. Although host-related IE risk factors have been identified, the involvement of bacterial features in IE complication is still unclear. We characterized strictly defined IE and bacteremia isolates and searched for discriminant features. S. aureus isolates causing community-acquired, definite native-valve IE (n=72) and bacteremia (n=54) were collected prospectively as part of a French multicenter cohort. Phenotypic traits previously reported or hypothesized to be involved in staphylococcal IE pathogenesis were tested. In parallel, the genotypic profiles of all isolates, obtained by microarray, were analyzed by discriminant analysis of principal components (DAPC)(2). No significant difference was observed between IE and bacteremia strains, regarding either phenotypic or genotypic univariate analyses. However, the multivariate statistical tool DAPC, applied on microarray data, segregated IE and bacteremia isolates: IE isolates were correctly reassigned as such in 80.6% of the cases (C-statistic 0.83, P<0.001). The performance of this model was confirmed with an independent French collection IE and bacteremia isolates (78.8% reassignment, C-statistic 0.65, P<0.01). Finally, a simple linear discriminant function based on a subset of 8 genetic markers retained valuable performance both in study collection (86.1%, P<0.001) and in the independent validation collection (81.8%, P<0.01). We here show that community-acquired IE and bacteremia S. aureus isolates are genetically distinct based on subtle combinations of genetic markers. This finding provides the proof of concept that bacterial characteristics may contribute to the occurrence of IE in patients with S. aureus bacteremia

A four-surface schematic eye of macaque monkey obtained by an optical method

AbstractSchematic eyes for four Macaca fascicularis monkeys were constructed from measurements of the positions and curvatures of the anterior and posterior surfaces of the cornea and lens. All of these measurements were obtained from Scheimpflug photography through the use of a ray-tracing analysis. Some of these measurements were also checked (and confirmed) by keratometry and ultrasound. Gaussian lens equations were applied to the measured dimensions of each individual eye in order to construct schematic eyes. The mean total power predicted by the schematic eyes agreed closely with independent measurements based on retinoscopy and ultrasound results, 74.2 ± 1.3 (SEM) vs 74.7 ± 0.3 (SEM) diopters. The predicted magnification of 202 μm/deg in one eye was confirmed by direct measurement of 205 μm/deg for a foveal laser lesion. The mean foveal retinal magnification calculated for our eight schematic eyes was 211 ± (SEM) μm/deg, slightly less than the value obtained by application of the method of Rolls and Cowey [Experimental Brain Research, 10, 298–310 (1970)] to our eight eyes but just 4% more than the value obtained by application of the method of Perry and Cowey [Vision Research, 12, 1795–1810 (1985)]

The Athena X-ray Integral Field Unit: a consolidated design for the system requirement review of the preliminary definition phase

The Athena X-ray Integral Unit (X-IFU) is the high resolution X-ray spectrometer, studied since 2015 for flying in the mid-30s on the Athena space X-ray Observatory, a versatile observatory designed to address the Hot and Energetic Universe science theme, selected in November 2013 by the Survey Science Committee. Based on a large format array of Transition Edge Sensors (TES), it aims to provide spatially resolved X-ray spectroscopy, with a spectral resolution of 2.5 eV (up to 7 keV) over an hexagonal field of view of 5 arc minutes (equivalent diameter). The X-IFU entered its System Requirement Review (SRR) in June 2022, at about the same time when ESA called for an overall X-IFU redesign (including the X-IFU cryostat and the cooling chain), due to an unanticipated cost overrun of Athena. In this paper, after illustrating the breakthrough capabilities of the X-IFU, we describe the instrument as presented at its SRR, browsing through all the subsystems and associated requirements. We then show the instrument budgets, with a particular emphasis on the anticipated budgets of some of its key performance parameters. Finally we briefly discuss on the ongoing key technology demonstration activities, the calibration and the activities foreseen in the X-IFU Instrument Science Center, and touch on communication and outreach activities, the consortium organisation, and finally on the life cycle assessment of X-IFU aiming at minimising the environmental footprint, associated with the development of the instrument. Thanks to the studies conducted so far on X-IFU, it is expected that along the design-to-cost exercise requested by ESA, the X-IFU will maintain flagship capabilities in spatially resolved high resolution X-ray spectroscopy, enabling most of the original X-IFU related scientific objectives of the Athena mission to be retained. (abridged).Comment: 48 pages, 29 figures, Accepted for publication in Experimental Astronomy with minor editin

The Athena X-ray Integral Field Unit: a consolidated design for the system requirement review of the preliminary definition phase

The Athena X-ray Integral Unit (X-IFU) is the high resolution X-ray spectrometer studied since 2015 for flying in the mid-30s on the Athena space X-ray Observatory. Athena is a versatile observatory designed to address the Hot and Energetic Universe science theme, as selected in November 2013 by the Survey Science Committee. Based on a large format array of Transition Edge Sensors (TES), X-IFU aims to provide spatially resolved X-ray spectroscopy, with a spectral resolution of 2.5 eV (up to 7 keV) over a hexagonal field of view of 5 arc minutes (equivalent diameter). The X-IFU entered its System Requirement Review (SRR) in June 2022, at about the same time when ESA called for an overall X-IFU redesign (including the X-IFU cryostat and the cooling chain), due to an unanticipated cost overrun of Athena. In this paper, after illustrating the breakthrough capabilities of the X-IFU, we describe the instrument as presented at its SRR (i.e. in the course of its preliminary definition phase, so-called B1), browsing through all the subsystems and associated requirements. We then show the instrument budgets, with a particular emphasis on the anticipated budgets of some of its key performance parameters, such as the instrument efficiency, spectral resolution, energy scale knowledge, count rate capability, non X-ray background and target of opportunity efficiency. Finally, we briefly discuss the ongoing key technology demonstration activities, the calibration and the activities foreseen in the X-IFU Instrument Science Center, touch on communication and outreach activities, the consortium organisation and the life cycle assessment of X-IFU aiming at minimising the environmental footprint, associated with the development of the instrument. Thanks to the studies conducted so far on X-IFU, it is expected that along the design-to-cost exercise requested by ESA, the X-IFU will maintain flagship capabilities in spatially resolved high resolution X-ray spectroscopy, enabling most of the original X-IFU related scientific objectives of the Athena mission to be retained. The X-IFU will be provided by an international consortium led by France, The Netherlands and Italy, with ESA member state contributions from Belgium, Czech Republic, Finland, Germany, Poland, Spain, Switzerland, with additional contributions from the United States and Japan.The French contribution to X-IFU is funded by CNES, CNRS and CEA. This work has been also supported by ASI (Italian Space Agency) through the Contract 2019-27-HH.0, and by the ESA (European Space Agency) Core Technology Program (CTP) Contract No. 4000114932/15/NL/BW and the AREMBES - ESA CTP No.4000116655/16/NL/BW. This publication is part of grant RTI2018-096686-B-C21 funded by MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe”. This publication is part of grant RTI2018-096686-B-C21 and PID2020-115325GB-C31 funded by MCIN/AEI/10.13039/501100011033

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Hypoxie et ingénierie tissulaire du cartilage (Thèse soutenue sur un ensemble de travaux)

Dans un contexte de vieillissement important de la population, la prévalence et le retentissement socio-économique de l arthrose sont en perpétuelle augmentation. Le cartilage articulaire possède un très faible pouvoir de régénération et les techniques actuelles ne permettent pas de régénérer un tissu fonctionnel, d où l orientation actuelle vers l'ingénierie tissulaire qui a pour objectif de fabriquer du cartilage in vitro. Cette stratégie innovante consiste à associer des cellules à un inducteur de la chondrogenèse et à un matériau qui servira d'échafaudage pour la synthèse de la matrice in vitro. Le cartilage artificiel pourra ensuite être réimplanté au niveau de la lésion chez le patient. Deux approches sont aujourd hui envisagées avec, d une part, l utilisation de chondrocytes et, d autre part, le recours aux cellules souches. Au cours de ce travail, nous avons associé ces cellules à une culture en hypoxie afin de mimer l environnement naturel du cartilage. Nos résultats, in vitro et in vivo, démontrent clairement le puissant effet inducteur de l hypoxie sur le phénotype chondrocytaire. De même, ils mettent en évidence les différents mécanismes moléculaires induits par le facteur de transcription clé HIF-1a ainsi que le rôle de SOX9 dans le maintien et la restauration du phénotype cartilagineux.In a context of important ageing of the population, prevalence and socioeconomic repercussion of the degenerative osteoarthritis are in perpetual increase. The cartilage has a very low regeneration potential and the current approaches do not allow to regenerate a fully functional tissue. Thus numerous study turned toward tissue engineering with the aim of making cartilage in vitro. This innovative strategy consists in associating cells with a chondrogenic inductor and a matrix, which will serve as a scaffold for in vitro tissue synthesis in vitro. Thereafter, the artificial cartilage undergoes implantation in the lesion of the patient. Nowadays, two approaches are envisaged with, on one hand, the use of chondrocytes and, on the other hand, the resort to stem cells. In this study, we have associated these cells with hypoxia to mimic the natural environment of the cartilage. Our results, both in vitro and in vivo, clearly demonstrate the powerful inductive effect of hypoxia on chondrocytic phenotype. They also enlighten HIF-1a molecular mechanisms and the role of SOX9 in cartilage phenotype maintain and recovery.CAEN-BU Sciences et STAPS (141182103) / SudocSudocFranceF

Dynamics of metal uptake by charged soft biointerphases: impacts of depletion, internalisation, adsorption and excretion

International audienceA comprehensive theory is elaborated for the dynamics of metal ion uptake by charged spherical microorganisms. The formalism integrates the interplay over time between bulk metal depletion, metal adsorption, metal excretion (efflux) and transport of metals by conductive diffusion toward the metal-consuming biomembrane. The model further involves the basic physicochemical features of the microbial interphase in terms of size, distribution of electrostatic charges and thickness of peripheral soft surface appendage. A generalization of the Best equation is proposed and leads to the expression of the time-dependent concentration of metal ions at the active membrane surface as a function of bulk metal concentration. Combination of this equation with the metal conservation condition over the sample volume allows a full evaluation of bulk metal depletion kinetics and the accompanying time-dependent uptake and excretion fluxes as a function of metal-microorganism electrostatic interaction, microbe concentration and relevant biophysicochemical features of the interphase. Practically tractable expressions are derived in the limit where the Biotic Ligand Model (BLM) is obeyed and in situations where conductive diffusion transport of metals significantly determines the rate of biouptake. In particular, the plateau value reached at sufficiently long times by bulk metal concentration is rigorously expressed in terms of the key parameters pertaining to the adsorption process and to the kinetics of metal uptake and excretion. The theory extends and unifies previous approximate models where the impacts of extracellular metal transport and/or metal efflux on the overall rate of uptake were ignored

Kinetic and thermodynamic determinants of trace metal partitioning at biointerphases: the role of intracellular speciation dynamics

International audienceThere is a large body of work evidencing the necessity to evaluate chemical speciation dynamics of trace metals in solution for an accurate definition of their bioavailability to microorganisms. In contrast, the integration of intracellular metal speciation dynamics in biouptake formalisms is still in its early stages. Accordingly, we elaborate here a rationale for the interplay between chemodynamics of intracellular metal complexes and dynamics of processes governing metal biouptake under non-complexing outer medium conditions. These processes include the conductive diffusion of metal ions to the charged soft biointerphase, metal internalisation, excretion of intracellular free metal species and metal depletion from bulk solution. The theory is formulated from Nernst–Planck equations corrected for electrostatic and reaction kinetic terms applied at the biosurface and in the intracellular volume. Computational illustrations demonstrate how biointerfacial metal distribution dynamics inherently reflects the chemodynamic properties of intracellular complexes. In the practical limits of high and weak metal affinity to biosurface internalisation sites, the metal concentration profile is explicitly solved under conditions of strong intracellular complexing agents. Exact analytical expression is further developed for metal partitioning at equilibrium. This provides a way to evaluate the metal biopartition coefficient from refined analysis of bulk metal depletion measured at various cell concentrations. Depending on here-defined dimensionless parameters involving rates of metal internalisation–excretion and complex formation, the formalism defines the nature of the different kinetic regimes governing bulk metal depletion and biouptake. In particular, the conditions leading to an internalisation flux limited by diffusion as a result of demanding intracellular metal complexation are identified

Relationship between Swelling and the Electrohydrodynamic Properties of Functionalized Carboxymethyldextran Macromolecules

International audienc