Oskar Bordeaux
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J Clin Sleep Med
No full textSTUDY OBJECTIVES: Objective sleepiness is an important outcome requiring rigorous evaluation regarding OSA treatment efficacy, but no systematic review has explored the efficacy of advancement treatments of the stomatognathic system (ATSS), i.e. mandibular advancement device (MAD), hypoglossal nerve stimulation (HNS), and maxillomandibular advancement surgery (MMA), on objective sleepiness in OSA. METHODS: We conducted a systematic review of the literature using PubMed, Scopus and Web of Science databases. All clinical studies assessing the efficacy of ATSS on objective sleepiness in adults with OSA, by the maintenance of wakefulness test (MWT), the multiple sleep latency test (MSLT), the Oxford sleep resistance test (OSLER), the psychomotor vigilance task (PVT) or the sustained attention to response task (SART), were included. RESULTS: Among 42 screened studies, 11 were included - 6 randomized controlled trials (RCTs) and 5 prospective studies. Regarding the RCTs, all assessed MAD efficacy and only one RCT found a significant improvement of objective sleepiness for MAD compared with placebo, on the MSLT. In the remaining RCTs, the included participants did not present objective sleepiness at baseline and were mostly with mild/moderate OSA. Regarding the prospective studies, all found a significant improvement of objective sleepiness for each treatment assessed, i.e. MAD, HNS, MMA and submental stimulation. Interestingly, the included participants presented objective sleepiness at baseline and moderate/severe OSA. CONCLUSIONS: This systematic review highlighted the lack of RCTs assessing the efficacy of MAD or other ATSS on objective sleepiness in OSA. Further RCTs are needed to address this important outcome taking into account baseline objective sleepiness and OSA severity
BMC Med Genomics
No full textFetal pleural effusions can arise in various contexts with different prognosis. They have been reported in fetuses presenting with hereditary or acquired conditions. One particularly rare genetic disorder, known as Knobloch syndrome, seems to emerge as a potential new cause of fetal pleural effusions, associated with severe outcomes. Knobloch syndrome 1 can be caused by biallelic variants in COL18A1. It is primarily characterized by its ophthalmic features, including severe vitreoretinal degeneration with retinal detachment and macular abnormalities. Neurological defects such as encephalocele and developmental delay, along with skeletal and renal malformations, are also associated with the syndrome. The Knobloch syndrome 2 is caused by monoallelic variants in the kinase domain of PAK2. It is less described and seems to also be associated with cardiac and respiratory damage in addition to the Knobloch syndrome 1 phenotype. PAK2 is a ubiquitous protein with a major implication in regulation and remodeling of the cytoskeleton and numerous other cellular pathways. Knobloch-associated variants seem to cause a loss of the kinase function of the protein. Even if the ophthalmic defects are almost constant, PAK2-associated Knobloch syndrome has slightly different features from Knobloch syndrome 1 in which pulmonary and lymphatic damages are still unseen. In a prenatal trio exome sequencing, we identified a novel de novo PAK2 missense variant, NM_002577.4:c.836 A > C, p.(Gln279Pro), classified as likely pathogenic in a 24 weeks of gestation fetus whose only sign was severe bilateral pleural effusion. From a literature review of patients, we recognize this sign as an important antenatal indicator of Knobloch syndrome 2, as it was the first sign identifiable in 2 out of 5 patients. This adds new evidence for the implication of this gene in fetal pleural effusions, with potentially severe outcomes
Surfactants: What are they and where are they hidden?
No full textLes tensioactifs, comme leur nom l’indique, regroupent des molécules capables de se positionner à l’interface entre deux milieux non miscibles, tels que l’eau et l’air, ou l’eau et l’huile, et d’agir sur les interactions moléculaires entre ces deux milieux. Chimiquement, ces molécules actives possèdent deux parties : une partie hydrophile, soluble dans l’eau, et une partie hydrophobe, souvent constituée de chaînes hydrocarbonées ou fluorocarbonées, qui interagit avec les substances apolaires comme les graisses ou huiles. Ce caractère amphiphile leur permet ainsi de s’accumuler à l’interface entre deux milieux non miscibles. Ce positionnement, associé à leurs caractéristiques physico-chimiques, est à l’origine de leur action sur la tension de surface ou tension interfaciale. L’effet du tensioactif se traduit par une diminution de cette tension, c’est-à-dire de l’énergie nécessaire pour maintenir l’interface, modifiant ainsi les interactions moléculaires entre les deux phases. En l’absence de tensioactif, la tension interfaciale entre deux phases non miscibles est importante en raison des forces cohésives au sein de chaque milieu, et des faibles interactions entre les molécules d’une phase avec celles de l’autre phase. La tension interfaciale élevée résulte en la formation de couches distinctes correspondant chacune à l’une des phases. À titre d’exemple, afin de minimiser la surface de contact huile/eau, une goutte d’huile reste sphérique lorsqu’elle est ajoutée à une solution aqueuse. Lorsque le volume de la phase huileuse est augmenté, les gouttelettes auront tendance à coalescer de façon à minimiser rapidement l’énergie interfaciale. En présence de tensioactifs s’accumulant entre les deux phases, les forces d’interaction au sein de chaque phase sont perturbées, la tension interfaciale est réduite. Les gouttelettes d’huile dispersées dans une phase aqueuse auront moins de propension à se regrouper, réduisant ainsi la séparation des phases. L’addition de tensioactifs dans une solution peut ainsi permettre la dispersion d’une phase dans une autre phase liquide (émulsion), ou même la stabilisation de particules solides en suspension. Selon que les tensioactifs portent ou non une charge sur leur partie hydrophile, et selon la nature de cette charge, ils sont classés en 4 grandes familles : les tensioactifs anioniques, cationiques, non ioniques ou zwittérioniques. Chacune de ces familles trouve de nombreuses applications dans notre vie quotidienne. Notons que face aux tensioactifs classiques décrits ci-dessus, certaines molécules complexes, comme des protéines, sont également utilisées en industrie pour leurs propriétés tensioactives. Les tensioactifs sont essentiellement utilisés pour leurs propriétés de solubilisation, de stabilisation de phases, émulsifiantes ou moussantes. En dessous d’une certaine concentration appelée concentration micellaire critique (CMC), les tensioactifs sont principalement sous forme monomoléculaire. Au-delà de la CMC, ils forment des micelles. En solution aqueuse, ces structures auto-assemblées correspondent à des organisations moléculaires dans lesquelles les parties hydrophobes se rejoignent au centre afin de limiter leur contact avec le solvant polaire. Les parties hydrophiles sont exposées à l’extérieur de la structure et établissent donc des interactions avec l’eau. Ainsi, les micelles de tensioactifs trouvent une application dans les solutions à effet détergent pour l’élimination des graisses et huiles, en emprisonnant ces composés apolaires en leur cœur et en évitant leur coalescence. Il est à noter qu’en solvant apolaire, les tensioactifs forment des micelles inversées, avec leur tête hydrophile orientée vers l’intérieur de la structure. La valeur de la CMC dépend à la fois de la structure du tensioactif (longueur, degré de saturation et de ramification des chaînes, charge et taille de la tête polaire) et des propriétés (notamment la force ionique pour les tensioactifs portant une charge, température pour les tensioactifs non ioniques) et de composition du milieu. La valeur de la CMC dans la formulation finale définira la concentration du tensioactif efficace dans la solution détergente. Comme indiqué plus haut, outre leur utilisation dans les produits ménagers visant à éliminer des substances apolaires comme les graisses et huiles, les tensioactifs sont également utiles pour la formation d’émulsions et de mousses. La formulation de différents produits alimentaires, cosmétiques ou pharmaceutiques requiert fréquemment le mélange de phases initialement non miscibles, mais qui permettent chacune la solubilisation de principes actifs ou aliments différents et complémentaires. En dessous de la CMC, l’émulsion formée peut être instable. Au-delà de la CMC, les émulsions produites sont plus stables et permettront la production de crèmes à usage cosmétique ou de sauces alimentaires par exemple. La capacité de certains tensioactifs à stabiliser des mousses, systèmes dans lesquels un gaz est dispersé dans un liquide, associée à leurs propriétés détergentes, trouvera des applications pour l’hygiène corporelle par exemple (shampoings, savons, etc.), ou dans le domaine alimentaire. Enfin, les micelles offrent un espace d’encapsulation où des molécules d’intérêt cosmétique ou pharmaceutique peuvent être dispersées, augmentant ainsi leur solubilité et leur stabilité. L’omniprésence des tensioactifs dans des produits d’hygiène (détergents, adoucissants, savons, shampoings), alimentaires, et cosmétiques témoigne de leur importance et de leur polyvalence. Cependant, cette large exposition de l’Homme à une variété de tensioactifs d’origine synthétique pouvant provoquer des irritations cutanées ou des réactions allergiques, n’est pas sans poser certaines questions, notamment en matière de santé.Surfactants are molecules capable of positioning themselves at the interface between two immiscible media, such as the water/air interface or the water/oil interface, and of acting on the molecular interactions between these two media. Chemically, these active molecules have two parts: a hydrophilic part, soluble in water, and a hydrophobic part, often made up of hydrocarbon or fluorocarbon chains, which interact with nonpolar substances such as fats or oils. This amphiphilic character allows them to accumulate at the interface between two immiscible media. This positioning, combined with their physicochemical properties, is the origin of their action on surface or interfacial tension. The effect of the surfactant results in a reduction of this tension, i.e., the energy required to maintain the interface, thus altering the molecular interactions between the two phases. In the absence of surfactants, the interfacial tension between two immiscible phases is high due to cohesive forces within each medium and weak interactions between molecules of one phase and those of the other phase. The high interfacial tension results in the formation of distinct layers, each corresponding to one of the phases. For example, to minimize the contact surface between oil and water, a drop of oil remains spherical when added to an aqueous solution. When the volume of the oil phase is increased, droplets tend to coalesce in order to quickly minimize the interfacial energy. In the presence of surfactants accumulating between the two phases, the interaction forces within each phase are disturbed, and the interfacial tension is reduced. The oil droplets dispersed in an aqueous phase are less likely to regroup, thus reducing phase separation. The addition of surfactants to a solution can thus enable the dispersion of one phase into another liquid phase (emulsion), or even the stabilization of solid particles in suspension. Surfactants are classified into four main families, depending on whether or not they carry a charge on their hydrophilic part, and based on the nature of this charge: anionic, cationic, nonionic, or zwitterionic surfactants. Each of these families finds numerous applications in our daily lives. It is worth noting that, alongside the classic surfactants described above, some complex molecules, such as proteins, are also used in industry for their surfactant properties. Surfactants are mainly used for their solubilizing, phase-stabilizing, emulsifying, or foaming properties. Below a certain concentration, called the critical micelle concentration (CMC), surfactants are mainly in monomolecular form. Beyond the CMC, they form micelles. In aqueous solution, these self-assembled structures correspond to molecular organizations in which the hydrophobic parts gather at the center to limit their contact with the polar solvent, while the hydrophilic parts are exposed to the outside of the structure and interact with water. Thus, surfactant micelles find applications in detergent solutions for the removal of fats and oils by trapping these nonpolar compounds in their core and preventing their coalescence. It is important to note that in a nonpolar solvent, surfactants form inverted micelles, with their hydrophilic head oriented toward the inside of the structure. The CMC value depends on both the structure of the surfactant (length, degree of saturation and branching of chains, charge and size of the polar head) and the properties (notably ionic strength for charged surfactants, temperature for nonionic surfactants) and composition of the medium. The CMC value in the final formulation will define the effective surfactant concentration in the detergent solution. As mentioned earlier, in addition to their use in household products designed to remove nonpolar substances like fats and oils, surfactants are also useful for forming emulsions and foams. The formulation of various food, cosmetic, or pharmaceutical products often requires the mixing of initially immiscible phases, each of which allows for the solubilization of different and complementary active ingredients or foods. Below the CMC, the emulsion formed may be unstable. Beyond the CMC, the emulsions produced are more stable and allow for the production of creams for cosmetic use or sauces for food. The ability of certain surfactants to stabilize foams, systems in which a gas is dispersed in a liquid, combined with their detergent properties, will find applications in personal hygiene products (shampoos, soaps, etc.) or in the food industry. Finally, micelles provide a space for encapsulation where molecules of cosmetic or pharmaceutical interest can be dispersed, increasing their solubility and stability. The widespread presence of surfactants in hygiene products (detergents, fabric softeners, soaps, shampoos), food, and cosmetics underscores their importance and versatility. However, this broad exposure of humans to a variety of synthetic surfactants, which can cause skin irritation or allergic reactions, raises some concerns, particularly regarding health
Bacterial conjugation in the ruminant pathogen Mycoplasma agalactiae is influenced by eukaryotic host factors
No full textHorizontal gene transfer (HGT) plays a pivotal role in the evolution and adaptation of genome-reduced mycoplasmas. The conjugative properties of these organisms are key in this phenomenon but are largely understudied, particularly in vivo . In the present study, the ruminant pathogen Mycoplasma agalactiae was used as a model organism to document mycoplasma conjugation in environments of increasing complexity, from axenic to cell and organotypic culture conditions. Compared to axenic mating conditions, mycoplasma co-cultivation with goat epithelial cells or bovine precision-cut lung slices resulted in enhanced mating frequencies with high rates of M. agalactiae integrative and conjugative element (ICEA) self-dissemination. These results were conditioned by the presence of eukaryotic cells in the culture and influenced by competition between mating partners but were not limited to M. agalactiae , as similar results were observed with Mycoplasma bovis . Mycoplasma conjugation ex vivo was further characterized by analyzing mycoplasma chromosomal transfer (MCT), a newly discovered mechanism of horizontal exchange of chromosomal DNA that generates mosaic genomes. Compared to ICEA transfer, MCT was detected at lower rates under cell and organotypic culture conditions, suggesting a negative impact of these cellular environments on MCT or its progeny. Finally, mating experiments under nutrient-deprived conditions identified nucleotide stress as a potential factor influencing the modulation of mycoplasma conjugation by eukaryotic host cells. In conclusion, these results suggest that HGT in vivo is likely underestimated and provide valuable models to further study mycoplasma conjugation ex vivo . IMPORTANCE Conjugation is an evolutionary shortcut that bacteria use to exchange genetic information with their neighbors. Despite the fast evolution rate of the genome-reduced mycoplasmas, their conjugative properties remain largely understudied, particularly in vivo . Here we used the ruminant pathogen Mycoplasma agalactiae to study how mycoplasmas conjugate in co-culture with host-derived cells and tissues. Interestingly, conjugation was stimulated when mycoplasmas were co-cultured with eukaryotic cells. This was documented by monitoring the self-propagation of a mobile genetic element known as integrative and conjugative element (ICE) and the exchange of chromosomal DNA leading to the formation of mosaic genomes. While ICE transfer was observed at high frequency, only a few mosaic genomes were detected in the presence of eukaryotic cells. Further data point toward nucleotide stress as a possible factor modulating mycoplasma conjugation in cellular environments. These results suggest that mycoplasma-host interactions may stimulate conjugation in vivo .Approche rationnelle d'un vaccin Mycoplasma bovi
BMC Geriatr
Full text linkBackground Frailty and impairment in intrinsic capacity (IC) have been shown to increase the risk of poor outcomes in older people. We aimed to determine the prevalence of frailty and its association with decline in IC among people aged 60 and over in Cameroon. Methods This cross-sectional study included community-dwellers aged >= 60 years. Frailty was assessed using Fried's criteria and IC decline using step 1 of the Integrated Care for Older People (ICOPE). Any abnormality reported for one of the six IC domains was considered as a positive screening. The significance level was p < 0.05. Results Among 108 participants included (64.8% women, median age 70 years (65-75)), all had a decline of at least one IC. The prevalence of frailty was 52.8%.The main domains involved were cognition (93.5%), vision (88%) and hearing (87%). Compared to participants without frailty, the frail group was older, achieved lower education, had fewer children, had a more frequent history of falls and a higher number of deficits in IC domains. In the multivariable model, after adjusting for age, sex and comorbidities, the participants with preserved mobility (OR 0.18, 95%CI 0.068-0.49) and vitality (OR 0.11 95%CI 0.04-0.28) were likely to have a lower risk of frailty. Conclusion Frailty and IC impairment were common in this group of older Cameroonians. Further research with the monitoring of trajectories of IC and frailty as a research outcome may allow better comparison to tailor interventions taking into account our local resources. Clinical trial numberNot applicable
Génération et utilisation de graphes de connaissances pour aider à la contextualisation des données de métabolomique
No full textCet article présente une e-infrastructure de graphes de connaissances, le "Metabolomic Semantic Data Lake", pour contextualiser les données métabolomiques. Elle relie des concepts biologiques et annote la littérature scientifique grâce à des méthodes issues de l'intelligence artificielle, palliant le manque d'annotation dans certains domaines. Basée sur des technologies Big Data et le Web Sémantique, elle offre une API pour un accès facile aux données. Les graphes FORVM ChemDisease et FORVM Plants permettent d'analyser des voies toxicologiques et d'identifier des biomarqueurs végétaux. L'objectif est d'améliorer l'intégration et l'interprétation des données en sciences de la vie.This article introduces a knowledge graph e-infrastructure, the Metabolomic Semantic Data Lake, for contextualizing metabolomics data. It links biological concepts and annotated scientific literature using AI, addressing annotation gaps. Based on Big Data technologies and the Semantic Web, it offers an API for easy data access. FORVM ChemDisease and FORVM Plants graphs enable the analysis of toxicological pathways and the identification of plant biomarkers. The aim is to enhance data integration and interpretation in life sciences.Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovationNext generation metabolomics and fluxomics, from population to single cellsMetaboHUB National Infrastructure of metabolomics and fluxomic
Environmental Gamma Dose Rate Measurements using CZT Detectors
No full textAbstract. The accurate and precise determination of the environmental dose rate is pivotal in every trapped-charge dating study. The environmental gamma-dose rate component can be determined from radionuclide concentrations using conversion factors or directly measured in situ with passive or active detectors. In-field measurements with an active detector are usually inexpensive and straightforward to achieve with adequate equipment and calibration. However, despite the rather widespread use of portable NaI or LaBr3 scintillator detectors, there is a lack of research on the performance and practicality of portable alternative detectors in dating studies, particularly in light of newer developments in the semi-conductor industry. Here, we present our experience with two small portable semi-conductor detectors housing Cadmium Zinc Telluride (CZT) crystals. Given their small volume and low power consumption, we argue they present attractive alternatives for gamma-dose rate measurements in dating studies. Despite high relative detection efficiency, their small volume may pose different challenges, resulting in impractical measurements in routine studies and, therefore need investigation. In our study, we simulated the particle interaction of the CZT crystal with GEANT4 in different sediment matrices to quantify the energy threshold in the spectrum above which the count/energy-count rate correlates with the environmental gamma dose-rate irrespective of the origin of the gamma-photons. We compared these findings with experimentally derived cumulative spectra and dose-rate calibration curves constructed from reference sites in France and Germany, which yielded unrealistically low threshold values likely due to the limited variability of the investigated sites. We additionally report negligible equipment background and required minimal measurement time of only 20 min in typical environments. Cross-checking our calibration on a homogenous loess deposit near Heidelberg confirmed the setting and assumed performance through a nearly identical gamma-dose rate of 1107 ± 65 µGy a−1 (CZT) to 1105 ±11 µGy a−1 (laboratory). The outcome of our study gives credit to our threshold definition. It validates the similarity of the two investigated probes, which may make it straightforward for other laboratories to implement the technique effortlessly. Finally, the implementation of CZT detectors has the potential to streamline fieldwork and enhance accuracy and precision of trapped-charge dating-based-chronologies
Br J Clin Pharmacol
Full text linkAimsPrednisone is a widely used glucocorticoid in the treatment of lupus, although its dosing is often determined empirically. Prednisolone, the active metabolite of prednisone, is found in its free form in the serum. The goal of this study was to develop a population pharmacokinetic model in patients with systemic lupus erythematosus (SLE) to forecast free prednisolone concentrations and its association with disease activity.MethodsA total of 66 active SLE patients (adults and children) were included, and followed up prospectively (242 observations available). Plasma prednisolone concentrations were assessed using liquid chromatography-mass spectrometry, and the data were analysed using Monolix software. The pharmacokinetic model was a one-compartment open model with absorption lag time representing the delay for both absorption and metabolism from inactive (prednisone) to active form (prednisolone). This model predicted free concentrations, which were then used to calculate total concentrations based on established binding constants.ResultsFree prednisolone clearance (CLu/F) and volume of distribution (Vu/F) were scaled allometrically to body weight. The typical population estimates (95% confidence interval) were 54 (48-62) L/h/70 kg and 235 (203-274) L/70 kg, respectively. Additionally, the bioavailability parameter was found to decrease non-linearly with the dose. Prednisolone cumulative exposure was not different between patients who responded at 3 months and those who did not.ConclusionsRobust pharmacokinetic targets are not yet clearly defined regarding toxicity or efficacy and are warranted in order to make a valuable contribution to prednisolone therapeutic drug monitoring in the context of SLE
Droit de la peine. Libération conditionnelle - Condamné libre (Cass. crim., 26 févr. 2025, n°24-80.823, B : JurisData n°2025-001800)
No full textBMC Pregnancy Childbirth
No full textBACKGROUND: While the global prevalence of smoking during pregnancy is 1.7%, it rises to 8.1% in Europe, where it is the main modifiable risk factor for morbidity and mortality during pregnancy. However, pregnancy is a key time to implement smoking cessation interventions, as women are more likely to adopt health-promoting behaviours during this period. Despite the availability of resources (e.g. policies, tools) and strategies (e.g. nicotine replacement therapy) to address smoking, their implementation remains neither optimal nor systematic. To address this, a multi-disciplinary multi-professional team developed the 5A-QUIT-N intervention to promote smoking cessation in pregnant women, by mobilising health professionals and optimising existing resources. Rather than creating new resources, the intervention uses existing tools and strategies and better integrates them into the pregnancy monitoring process. This article describes the development and operationalisation of the 5A-QUIT-N intervention. METHODS: The development of the 5A-QUIT-N intervention involved three stages. First, its components were established according to national recommendations and a final list was validated by a scientific committee. Next, obstacles and levers that could influence their implementation and effectiveness were identified through a scoping review and semi-structured interviews. The resulting data were then used to design the first version of the intervention. RESULTS: Findings from the literature and field experiences highlighted the need for better mobilisation and coordination of the existing resources. The 5A-QUIT-N intervention was developed to address these issues by improving resource organisation within each region. At the clinical level, it aims to enhance healthcare professionals' skills in smoking cessation practices using existing resources. At the organisational level, it promotes closer coordination between perinatal and smoking cessation professionals. The involvement of local stakeholders and local resources is an integral part of the intervention, as these vary from one region to another. CONCLUSION: This intervention was made possible thanks to the combination of a literature search, a qualitative study, and commitment from stakeholders from grassroots level upwards