Recent publications
Dental health is frequently altered in patients with chronic kidney disease. We conducted a prospective study on dental health in CKD patients with a specific interest in the association between dental health issues and the accumulation of uremic toxins in the saliva. A total of 88 patients were included in the study, with chronic kidney disease stage 2 to 5 (without kidney replacement). We analysed the total concentrations of eight uremic toxins (trimethylamine N-oxide -TMAO-, Indoxyl Sulfate, P-cresyl-sulfate, Indole 3-acetic acid, 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid -CMPF-, Kynurenine, Hippuric acid and Phenylacetylglutamine) and three precursors of uremic toxins (Tyrosine, Phenylalanine and Tryptophan) in the saliva using LC-MS/MS. We observed, for the first time, the association between various dental scores: DMFT, FST, CPITN, and OHIS, and saliva uremic toxins and precursors: TMAO, indoxyl sulfate, or hippuric acid. Further prospective interventional studies are required to confirm our results.
To contain the spread of the SARS-CoV-2 pandemic, rapid development of vaccines was required in 2020. Rational design, international efforts, and a lot of hard work yielded the market approval of novel SARS-CoV-2 vaccines based on diverse platforms such as mRNA or adenovirus vectors. The great success of these technologies, in fact, contributed significantly to control the pandemic. Consequently, most scientific literature available in the public domain discloses the results of clinical trials and reveals data of efficaciousness. However, a description of processes and rationales that led to specific vaccine design is only partially available, in particular for adenovirus vectors, even though it could prove helpful for future developments. Here, we disclose our insights from the endeavors to design compatible functional adenoviral vector platform expression cassettes for the SARS-CoV-2 spike protein. We observed that contextualizing genes from an ssRNA virus into a DNA virus provides significant challenges. Besides affecting physical titers, expression cassette design of adenoviral vaccine candidates can affect viral propagation and spike protein expression. Splicing of mRNAs was affected, and fusogenicity of the spike protein in ACE2-overexpressing cells was enhanced when the ER retention signal was deleted.
Cannabidiol is the first cannabis-derived drug approved for the treatment of Lennox-Gastaut syndrome, Dravet syndrome, and Tuberous Sclerosis Complex. In the current study, we performed a descriptive analysis followed by a disproportionality analysis of potential adverse events caused by CBD extracted from the VigiBase® database. Furthermore, the biological plausibility of the association between CBD and the serotonin 5-HT1A receptor as a possible cause of adverse events was analyzed and discussed. Data were extracted from the VigiBase® database using the VigiLyze® signal detection and signal management tool. Adverse events in VigiBase® reports were coded using MedDRA, version 19 of Preferred Terms (PTs). Data were uploaded into SPSS software and analyzed via a disproportionality analysis. Statistically significant disproportionality signals for CBD were found for "weight decreased" (5.19 (95% CI: 4.54-5.70)), "hypophagia" (3.68 (95% CI: 3.22-5.27)), and "insomnia" (1.6 (95% CI: 1.40-1.83)). Positive IC025 values were found for "weight decreased" (2.2), "hypophagia" (1.3), and "insomnia" (0.5), indicating a surplus of reported cases. CBD's interactions with 5-HT1A serotonin receptors may offer a potential biological explanation for the occurrence of insomnia in patients. It is noteworthy that the risk profiles mentioned in the information for prescribing CBD as an antiepileptic agent by regulatory agencies showed disparities specifically related to the adverse event "insomnia".
(1) Background: Aspergillus flavus is a cosmopolitan mold with medical, veterinary, and agronomic concerns. Its morphological similarity to other cryptic species of the Flavi section requires molecular identification techniques that are not routinely performed. For clinical isolates of Aspergillus section Flavi, we present the molecular identification, susceptibility to six antifungal agents, and clinical context of source patients. (2) Methods: One hundred forty fungal clinical isolates were included in the study. These isolates, recovered over a 15-year period (2001–2015), were identified based on their morphological characteristics as belonging to section Flavi. After the subculture, sequencing of a part of the β-tubulin and calmodulin genes was performed, and resistance to azole antifungals was screened on agar plates containing itraconazole and voriconazole. Minimum inhibitory concentrations were determined for 120 isolates by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) broth microdilution method. (3) Results: Partial β-tubulin and calmodulin sequences analysis showed that 138/140 isolates were A. flavus sensu stricto, 1 isolate was A. parasiticus/sojae, and 1 was A. nomiae. Many of the isolates came from samples collected in the context of respiratory tract colonization. Among probable or proven aspergillosis, respiratory infections were the most frequent, followed by ENT infections. Antifungal susceptibility testing was available for isolates (n = 120, all A. flavus ss) from one hospital. The MIC range (geometric mean MIC) in mg/L was 0.5–8 (0.77), 0.5–8 (1.03), 0.125–2 (0.25), 0.03–2 (0.22), 0.25–8 (1.91), and 0.03–0.125 (0.061) for voriconazole, isavuconazole, itraconazole, posaconazole, amphotericin B, and caspofungin, respectively. Two (1.67%) isolates showed resistance to isavuconazole according to current EUCAST breakpoints with MICs at 8 mg/L for isavuconazole and voriconazole. One of these two isolates was also resistant to itraconazole with MIC at 2 mg/L. (4) Conclusions: The present characterization of a large collection of Aspergillus belonging to the Flavi section confirmed that A. flavus ss is the predominant species. It is mainly implicated in respiratory and ENT infections. The emergence of resistance highlights the need to perform susceptibility tests on section Flavi isolates.
The amniotic membrane (AM) is the innermost part of the fetal placenta, which surrounds and protects the fetus. Due to its structural components (stem cells, growth factors, and proteins), AMs display unique biological properties and are a widely available and cost-effective tissue. As a result, AMs have been used for a century as a natural biocompatible dressing for healing corneal and skin wounds. To further increase its properties and expand its applications, advanced hybrid materials based on AMs have recently been developed. One existing approach is to combine the AM with a secondary material to create composite membranes. This review highlights the increasing development of new multilayer composite-based AMs in recent years and focuses on the benefits of additive manufacturing technologies and electrospinning, the most commonly used strategy, in expanding their use for tissue engineering and clinical applications. The use of AMs and multilayer composite-based AMs in the context of nerve regeneration is particularly emphasized and other tissue engineering applications are also discussed. This review highlights that these electrospun multilayered composite membranes were mainly created using decellularized or de-epithelialized AMs, with both synthetic and natural polymers used as secondary materials. Finally, some suggestions are provided to further enhance the biological and mechanical properties of these composite membranes.
Background:
While opportunistic infections are a frequent and challenging problem in kidney transplant recipients, their long-term epidemiology remains hardly known.
Methods:
Opportunistic infections were recorded in 1144 recipients transplanted in our center between 2004 and 2015. Incidence rates and baseline risk factors were determined using joint frailty models.
Results:
After a median follow-up of 5.6 years, 544 opportunistic infections occurred in 373/1144 (33%) patients, dominated by viral infections (396/544, 72%), especially CMV syndromes and diseases (213/544, 39%). A third of the infected patients experienced at least 2 opportunistic infections. The incidence of opportunistic infections was 10 times higher during the first year post-transplantation than afterwards (34.7 infections for 100 patient-years vs. 3.64). Opportunistic infections associated with the age of the donor (p = 0.032), the age of the recipient (p = 0.049), the CMV serostatus (p < 10-6), a higher class II HLA mismatch (p = 0.032), and an induction treatment including rabbit anti-thymocyte globulins (p = 0.026). Repeated opportunistic infections associated with each other (p < 10-6) and with renal death (p < 10-6).
Conclusion:
Opportunistic infections occur with a 2-period incidence pattern and many susceptible patients suffer from repeated episodes. This knowledge may help tailor new prevention and follow-up strategies to reduce the burden of opportunistic infections and their impact on transplantation outcome.
At Jupiter, part of the auroral radio emissions are induced by the Galilean moons Io, Europa and Ganymede. Until now, except for Ganymede, they have been only remotely detected, using ground-based radio-telescopes or electric antennas aboard spacecraft. The polar trajectory of the Juno orbiter allows the spacecraft to cross the range of magnetic flux tubes which sustain the various Jupiter-satellite interactions, and in turn to sample in situ the associated radio emission regions. In this study, we focus on the detection and the characterization of radio sources associated with Io, Europa and Ganymede. Using electric wave measurements or radio observations (Juno/Waves), in situ electron measurements (Juno/JADE-E), and magnetic field measurements (Juno/MAG) we demonstrate that the Cyclotron Maser Instability (CMI) driven by a loss-cone electron distribution function is responsible for the encountered radio sources. We confirmed that radio emissions are associated with Main (MAW) or Reflected Alfv\'en Wing (RAW), but also show that for Europa and Ganymede, induced radio emissions are associated with Transhemispheric Electron Beam (TEB). For each traversed radio source, we determine the latitudinal extension, the CMI-resonant electron energy, and the bandwidth of the emission. We show that the presence of Alfv\'en perturbations and downward field aligned currents are necessary for the radio emissions to be amplified.
Water vapour atmospheres with content equivalent to the Earth’s oceans, resulting from impacts¹ or a high insolation2,3, were found to yield a surface magma ocean4,5. This was, however, a consequence of assuming a fully convective structure2–11. Here, we report using a consistent climate model that pure steam atmospheres are commonly shaped by radiative layers, making their thermal structure strongly dependent on the stellar spectrum and internal heat flow. The surface is cooler when an adiabatic profile is not imposed; melting Earth’s crust requires an insolation several times higher than today, which will not happen during the main sequence of the Sun. Venus’s surface can solidify before the steam atmosphere escapes, which is the opposite of previous works4,5. Around the reddest stars (Teff < 3,000 K), surface magma oceans cannot form by stellar forcing alone, whatever the water content. These findings affect observable signatures of steam atmospheres and exoplanet mass–radius relationships, drastically changing current constraints on the water content of TRAPPIST-1 planets. Unlike adiabatic structures, radiative–convective profiles are sensitive to opacities. New measurements of poorly constrained high-pressure opacities, in particular far from the H2O absorption bands, are thus necessary to refine models of steam atmospheres, which are important stages in terrestrial planet evolution.
Fluctuation dynamos occur in most turbulent plasmas in astrophysics and are the prime candidates for amplifying and maintaining cosmic magnetic fields. A few analytical models exist to describe their behavior, but they are based on simplifying assumptions. For instance, the well-known Kazantsev model assumes an incompressible flow that is δ-correlated in time. However, these assumptions can break down in the interstellar medium as it is highly compressible and the velocity field has a finite correlation time. Using the renewing flow method developed by Bhat and Subramanian (2014), we aim to extend Kazantsev's results to a more general class of turbulent flows. The cumulative effect of both compressibility and finite correlation time over the Kazantsev spectrum is studied analytically. We derive an equation for the longitudinal two-point magnetic correlation function in real space to first order in the correlation time τ and for an arbitrary degree of compressibility (DOC). This generalized Kazantsev equation encapsulates the original Kazantsev equation. In the limit of small Strouhal numbers St∝τ we use the Wentzel-Kramers-Brillouin approximation to derive the growth rate and scaling of the magnetic power spectrum. We find the result that the Kazantsev spectrum is preserved, i.e., Mk(k)∼k3/2. The growth rate is also negligibly affected by the finite correlation time; however, it is reduced by the finite magnetic diffusivity and the DOC together.
Seven rocky planets orbit the nearby dwarf star TRAPPIST-1, providing a unique opportunity to search for atmospheres on small planets outside the Solar System¹. Thanks to the recent launch of the James Webb Space Telescope (JWST), possible atmospheric constituents such as carbon dioxide (CO2) are now detectable2,3. Recent JWST observations of the innermost planet TRAPPIST-1 b showed that it is most probably a bare rock without any CO2 in its atmosphere⁴. Here we report the detection of thermal emission from the dayside of TRAPPIST-1 c with the Mid-Infrared Instrument (MIRI) on JWST at 15 µm. We measure a planet-to-star flux ratio of fp/f⁎ = 421 ± 94 parts per million (ppm), which corresponds to an inferred dayside brightness temperature of 380 ± 31 K. This high dayside temperature disfavours a thick, CO2-rich atmosphere on the planet. The data rule out cloud-free O2/CO2 mixtures with surface pressures ranging from 10 bar (with 10 ppm CO2) to 0.1 bar (pure CO2). A Venus-analogue atmosphere with sulfuric acid clouds is also disfavoured at 2.6σ confidence. Thinner atmospheres or bare-rock surfaces are consistent with our measured planet-to-star flux ratio. The absence of a thick, CO2-rich atmosphere on TRAPPIST-1 c suggests a relatively volatile-poor formation history, with less than 9.5−2.3+7.5\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${9.5}_{-2.3}^{+7.5}$$\end{document} Earth oceans of water. If all planets in the system formed in the same way, this would indicate a limited reservoir of volatiles for the potentially habitable planets in the system.
Introduction:
In Bordeaux University Hospital, neurologists are required to prescribe thrombolysis using telemedicine (telethrombolysis) for anticoagulated stroke patients admitted in peripheral centers in the Nouvelle-Aquitaine region. However, due to the bleeding risk, the maximum concentration of DOAC authorizing thrombolysis is 30, 50 or 100 ng/mL (depending on the sources and the patient-specific benefit-risk ratio). Most of the time, specific assays of Direct Oral Anticoagulants (DOACs) are not available in these peripheral centers. We therefore studied an alternative test: the Unfractionated Heparin (UFH) anti-Xa activity which is available in most laboratories and could be used to estimate the DOAC concentration.
Methods:
Five centers were included in our study: three centers using the Liquid Anti-Xa HemosIL® Werfen reagent and two centers using the STA-Liquid Anti-Xa® Stago reagent. For each reagent, we established correlation curves between DOAC and UFH anti-Xa activities and determinated UFH cut-offs for the thresholds of 30, 50 and 100 ng/mL respectively.
Results:
A total of 1455 plasmas were tested. There is an excellent correlation between DOAC and UFH anti-Xa activities using a third-degree modeling curve, independently the reagent used. However, a significant inter-reagent variability is observed concerning the obtained cut-offs.
Conclusion:
Our study makes unsuitable the use of a universal cut-off. In opposition to recommendations made by other publications, the UFH cut-offs must be adapted to the reagent used locally by the laboratory, and to the considered DOAC.
El objetivo de este artículo es presentar una revisión de literatura que muestre la relevancia, evolución y tendencias sobre la producción científica relacionada con la supervivencia empresarial identificada en las bases de datos Web of Science y Scopus entre 1973 y 2020. Para los registros obtenidos se realizó un análisis de red apoyado en la teoría de grafos, aplicando herramientas como R, bibliometrix y Gephi que permiten identificar la importancia del tema y construir la evolución teórica de su abordaje usando los algoritmos de la herramienta Tree of Sciencie (TOS), con el cual se identifican documentos seminales, estructurales y tendencias, por medio del análisis de clusterización. Los resultados muestran cuatro subáreas de análisis de la supervivencia: desde el emprendimiento, las estrategias y la influencia de la innovación, las variables que influyen en ella y la tipología de salida en la bolsa de valores.
Close-in giant exoplanets with temperatures greater than 2,000 K ("ultra-hot Jupiters") have been the subject of extensive efforts to determine their atmospheric properties using thermal emission measurements from the Hubble and Spitzer Space Telescopes1-3. However, previous studies have yielded inconsistent results because the small sizes of the spectral features and the limited information content of the data resulted in high sensitivity to the varying assumptions made in the treatment of instrument systematics and the atmospheric retrieval analysis3-12. Here we present a dayside thermal emission spectrum of the ultra-hot Jupiter WASP-18b obtained with the NIRISS13 instrument on JWST. The data span 0.85 to 2.85 μm in wavelength at an average resolving power of 400 and exhibit minimal systematics. The spectrum shows three water emission features (at <6σ confidence) and evidence for optical opacity, possibly due to H-, TiO, and VO (combined significance of 3.8σ). Models that fit the data require a thermal inversion, molecular dissociation as predicted by chemical equilibrium, a solar heavy-element abundance ("metallicity", M/H = [Formula: see text] x solar), and a carbon-to-oxygen (C/O) ratio less than unity. The data also yield a dayside brightness temperature map, which shows a peak in temperature near the sub-stellar point that decreases steeply and symmetrically with longitude toward the terminators.
Understanding global space weather effects is of great importance to the international scientific community, but more localised space weather predictions are important on a national level. In this study, data from a ground magnetometer at Valentia Observatory is used to characterise space weather effects on the island of Ireland. The horizontal component of magnetometer observations and its time derivative are considered, and extreme values of these are identified. These extremes are fit to a generalised extreme value distribution, and from this model return values (the expected magnitude of an observation within a given time window) are predicted. The causes of extreme values are investigated both in a case study, and also statistically by looking at contributions from geomagnetic storms, substorms, and sudden commencements. This work characterises the extreme part of the distribution of space weather effects on Ireland (and at similar latitudes), and hence examines those space weather observations which are likely to have the greatest impact on susceptible technologies.
Age-related macular degeneration (AMD) is one of the most commonly occurring ocular diseases worldwide. This degenerative condition affects the retina and leads to the loss of central vision. The current treatments are focused on the late stage of the disease, but recent studies have highlighted the importance and benefits of preventive treatments and how good dietary habits can reduce the risk of progression to an advanced form of the disease. In this context, we studied whether resveratrol (RSV) or a polyphenolic cocktail, red wine extract (RWE), are able to prevent the initiating events of AMD (i.e., oxidative stress and inflammation) in human ARPE-19 retinal pigment epithelial (RPE) cells and macrophages. This study highlights that RWE and RSV can prevent hydrogen peroxide (H2O2) or 2,2′-Azobis(2-methylpropionamidine) dihydrochloride (AAPH)-induced oxidative stress and can subsequently prevent DNA damage via the inhibition of the ATM (ataxia telangiectasia-mutated)/Chk2 (checkpoint kinase 2) or Chk1 signaling pathways, respectively. Moreover, ELISA assays show that RWE and RSV can prevent the secretion of proinflammatory cytokines in RPE cells and in human macrophages. Interestingly, RWE exhibits a greater protective impact compared to RSV alone, even though RSV was more concentrated when used alone than in the red wine extract. Our results suggest that RWE and RSV may have potential interest as preventive nutritional supplementations against AMD.
Photochemistry is a fundamental process of planetary atmospheres that regulates the atmospheric composition and stability¹. However, no unambiguous photochemical products have been detected in exoplanet atmospheres so far. Recent observations from the JWST Transiting Exoplanet Community Early Release Science Program2,3 found a spectral absorption feature at 4.05 μm arising from sulfur dioxide (SO2) in the atmosphere of WASP-39b. WASP-39b is a 1.27-Jupiter-radii, Saturn-mass (0.28 MJ) gas giant exoplanet orbiting a Sun-like star with an equilibrium temperature of around 1,100 K (ref. ⁴). The most plausible way of generating SO2 in such an atmosphere is through photochemical processes5,6. Here we show that the SO2 distribution computed by a suite of photochemical models robustly explains the 4.05-μm spectral feature identified by JWST transmission observations⁷ with NIRSpec PRISM (2.7σ)⁸ and G395H (4.5σ)⁹. SO2 is produced by successive oxidation of sulfur radicals freed when hydrogen sulfide (H2S) is destroyed. The sensitivity of the SO2 feature to the enrichment of the atmosphere by heavy elements (metallicity) suggests that it can be used as a tracer of atmospheric properties, with WASP-39b exhibiting an inferred metallicity of about 10× solar. We further point out that SO2 also shows observable features at ultraviolet and thermal infrared wavelengths not available from the existing observations.
Calculating the pressure-strain terms has recently been performed to quantify energy conversion between the bulk flow energy and the internal energy of plasmas. It has been applied to numerical simulations and satellite data from the Magnetospheric MultiScale Mission. The method requires spatial gradients of the velocity and the use of the full pressure tensor. Here we present a derivation of the errors associated with calculating the pressure-strain terms from multi-spacecraft measurements and apply it to previously studied examples of magnetic reconnection at the magnetopause and the magnetotail. The errors are small in a dense magnetosheath event but much larger in the more tenuous magnetotail. This is likely due to larger counting statistics in the dense plasma at the magnetopause than in the magnetotail. The propagated errors analyzed in this work are important to understand uncertainties of energy conversion measurements in space plasmas and have applications to current and future multi-spacecraft missions.
Chromosomal rearrangements of the human KMT2A/MLL gene are associated with de novo as well as therapy-induced infant, pediatric, and adult acute leukemias. Here, we present the data obtained from 3401 acute leukemia patients that have been analyzed between 2003 and 2022. Genomic breakpoints within the KMT2A gene and the involved translocation partner genes (TPGs) and KMT2A-partial tandem duplications (PTDs) were determined. Including the published data from the literature, a total of 107 in-frame KMT2A gene fusions have been identified so far. Further 16 rearrangements were out-of-frame fusions, 18 patients had no partner gene fused to 5’-KMT2A, two patients had a 5’-KMT2A deletion, and one ETV6::RUNX1 patient had an KMT2A insertion at the breakpoint. The seven most frequent TPGs and PTDs account for more than 90% of all recombinations of the KMT2A, 37 occur recurrently and 63 were identified so far only once. This study provides a comprehensive analysis of the KMT2A recombinome in acute leukemia patients. Besides the scientific gain of information, genomic breakpoint sequences of these patients were used to monitor minimal residual disease (MRD). Thus, this work may be directly translated from the bench to the bedside of patients and meet the clinical needs to improve patient survival.
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