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Spatial mapping of rheumatoid arthritis synovial niches reveals specific macrophage networks associated with response to therapy
No full textAbstract Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease affecting peripheral joints and for which approximately 40% of the patients respond insufficiently to the available synthetic or biologic disease modifying anti-rheumatic drugs (DMARDs). The infiltration of the synovial membrane by lymphocytes and monocytes profoundly alters its homeostatic functions, leading to chronic joint inflammation and bone destruction. A better understanding of how DMARDs impact the complex synovial cell social network in relationship to response/ non-response remains an unmet need to design more targeted and active therapeutic strategies. Here, we used imaging mass cytometry (IMC) to comparatively profile more than 115,000 cells in the synovial tissue of healthy, low inflammatory osteoarthritis and matched active early treatment-naïve RA patients at baseline and at 6 months after starting DMARDs treatment. We notably highlighted that tissue resident macrophages (LYVE1 + CD206 + ) in perivascular synovial niches encompassing specific subsets of vascular cells, fibroblasts and immune cells vanished in active RA but were recovered in response to DMARDs treatment. Combined ligand-receptor analysis of single-cell RNA sequencing datasets identified that IL10, C-type lectin or TAM (TYRO3, AXL and MERTK) receptors were particularly involved in the restoration of these spatial cell interactions in the context of clinical remission. In addition to providing an unprecedented synovial spatial mapping, our work uncovered novel potential cellular and molecular targets for the development of therapies for RA. One Sentence Summary Single-cell spatial profiling of rheumatoid arthritis synovium identifies specific cell states linked to treatment respons
Participation à la création d'un registre terminologique de pathologie chirurgicale
No full textLa Terminologie est une discipline qui répertorie et conceptualise les termes d’un langage de spécialité. Elle participe à l’efficacité de toute communication, à l’apprentissage par stimulation de la cognition et remplit bien d’autres fonctions. Elle est ainsi indissociable de nombreux domaines comme la médecine vétérinaire et notamment la pathologie chirurgicale. La première partie de ce travail de thèse a ainsi pour objectif de présenter le processus terminologique afin d’offrir une vision globale et d’en comprendre les tenants et aboutissants. Ce dernier se divise en trois phases. La première, pré-terminographique, consiste en l’étude de la discipline, l’identification des objectifs et le rassemblement des ressources nécessaires. Elle est suivie par la phase terminographique, c’est-à-dire la rédaction du registre terminologique. Le processus s’achève avec la phase post-terminographique permettant la bonne continuité et le bon usage de l’outil terminologique. La deuxième partie de ce travail de thèse consiste en l’application de ce processus à la pathologie chirurgicale. L’étude des besoins et méthodes de travail des étudiants et vétérinaires vis-à-vis de la discipline révèle l’intérêt de créer une aide adaptée à la formation. Ainsi, malgré des limites principalement humaines, le registre terminologique pourrait s’insérer dans cette optique s’il est poursuivi
Étude de la régénération ostéochondrale par des techniques d'ingénierie tissulaire chez la brebis
No full textCette thèse explore la régénération ostéochondrale à travers l’évaluation d’implants biomimétiques biodégradables. L’objectif principal est de restaurer l’unité ostéochondrale par une approche moins invasive que l’autogreffe, en étudiant également l’intérêt de l’apport de facteurs de croissance. Les implants étudiés associent un hydrogel d’acide hyaluronique silanisé, mimant le cartilage hyalin, et un ciment macroporeux de phosphate de calcium, favorisant la régénération osseuse. Cette combinaison permet une reconstruction hiérarchisée et biomimétique de l’interface ostéochondrale. L’ajout de facteurs de croissance vise à stimuler la prolifération cellulaire, la chondrogenèse et l’ostéogenèse, optimisant ainsi l’intégration tissulaire et la récupération fonctionnelle. L’étude expérimentale, menée sur la brebis, modélise des défauts ostéochondraux du condyle fémoral médial. Plusieurs conditions sont comparées : défaut non traité, autogreffe et implant biodégradable, avec ou sans facteur de croissance. Les évaluations postopératoires visent à mesurer la stabilité, l’intégration et la régénération tissulaire. Les résultats confirment l’efficacité de l’autogreffe dans la régénération ostéochondrale. Les implants utilisés semblent en revanche non adaptés à la régénération ostéochondrale, de par les matériaux utilisés et leur forme d’application, qui ne permettent pas un bon maintien des implants dans le site donneur. Bien que les implants biodégradables étudiés ici n’atteignent pas l’efficacité fonctionnelle de l’autogreffe, ils restent une alternative prometteuse, moins invasive et adaptable, ouvrant la voie à de futures applications cliniques vétérinaires et humaines
Mieux communiquer autour de la nutrition : élaboration de documents pédagogiques à destination des propriétaires d'animaux de compagnie
No full textUne alimentation adaptée est essentielle à la santé des chiens et des chats, mais les propriétaires commettent fréquemment des erreurs nutritionnelles, souvent par manque d'informations claires et accessibles. Ces erreurs peuvent avoir des conséquences sur la santé, telles que l'obésité ou induire des carences nutritionnelles. Face à ce constat, il faut souligner l'importance de la vulgarisation scientifique pour mieux expliquer la nutrition aux propriétaires des chiens et des chats. L’objectif de ce travail est donc de transformer des informations scientifiques complexes en outils concrets, permettant aux propriétaires de devenir des acteurs éclairés de la santé nutritionnelle de leurs animaux. La première partie propose une synthèse bibliographique sur la vulgarisation scientifique, la physiologie nutritionnelle canine et féline, et les différents types d'aliments. La deuxième partie détaille la création de fiches pédagogiques innovantes, conçues spécifiquement pour les propriétaires. Enfin, la troisième partie présente une analyse approfondie de chaque fiche, justifiant les choix de contenu et de présentation pour une efficacité maximale. Ces fiches visent ainsi à transmettre des connaissances fiables et à déconstruire les idées reçues sur des sujets comme la fabrication des croquettes, la place des céréales ou les régimes dits "naturels"
Retrait vidéo-assisté réussi d'un corps étranger de type balle dans la vessie chez deux chats
No full textInternational audienceThis report describes the successful video-assisted removals of urinary bladder bullet foreign bodies in 2 cats. In both cases, the cat was presented because of chronic dysuria and hematuria. Diagnostic imaging, including radiography and ultrasonography, identified a foreign body in the bladder, confirmed as a lead pellet. Video-assisted percutaneous endoscopy was used for foreign body removal and bladder inspection. Both cats recovered uneventfully after surgery, with no postoperative complications. This report highlights the advantages of percutaneous and video-laparoscopic-assisted endoscopy in managing urinary bladder foreign bodies in small animals, providing reduced trauma and quick recovery.Key clinical message:Endoscope-assisted foreign body removal from the bladder seems to be a safe and efficient way to retrieve small foreign bodies in cats.Les corps étrangers vésicaux sont une cause rare mais peuvent provoquer des troubles urinaires et être potentiellement obstructif chez le chien et le chat. Deux chats ont présenté une dysurie chronique associée à une hématurie, chez lesquels l’imagerie médicale (radiographies et échographie abdominales) a permis d’identifier un corps étranger métallique intravésical compatible avec un plomb. Dans les deux cas, une prise en charge chirurgicale mini-invasive par cystoscopie percutanée vidéo-assistée a été réalisée afin de retirer le corps étranger et d’inspecter la muqueuse vésicale. La technique consistait en une mini-laparotomie médiane, la fixation de l’apex vésical à la paroi abdominale, puis l’introduction d’un endoscope rigide par un unique port intravésical servant à la fois de port optique et de port instrument. L’extraction du plomb a été réalisée à l’aide d’une pince de Hartmann sous contrôle endoscopique direct. Aucune complication per- ou postopératoire n’a été observée. Après 24 heures d’hospitalisation, les deux chats étaient confortables et présentaient une disparition complète des signes urinaires à court et long terme. Ces cas illustrent l’intérêt de la chirurgie mini-invasive dans la prise en charge des corps étrangers vésicaux chez le chat. L’approche vidéo-assistée permet une excellente visualisation, une réduction du traumatisme chirurgical et une convalescence rapide. Les corps étrangers doivent être envisagés comme diagnostic différentiel de cystite chronique chez les chats d’extérieur
Tracking invasion events: phylogeography of Hyalomma marginatum in the Mediterranean basin with a focus on Southern France
No full textInternational audienceHyalomma marginatum is a hard tick vector of various pathogens, including Crimean-Congo Hemorrhagic fever virus, recently detected in French specimens. This species has a wide distribution from North Africa to Eastern Europe and has only recently been considered established in Southern France. These changes in species distribution led us to explore the genetic structure of tick populations in the Mediterranean basin and attempt to infer the origin of French populations. Methods We used two mitochondrial markers (12S rRNA and Cytochrome Oxidase 1) and genotyped ticks from nine Mediterranean countries. We compared genetic indices and haplotypic composition between these countries and the various French geographical populations. Results Across all countries, we showed significant genetic differentiation, with a certain proximity between neighboring countries. We found very different genetic compositions among the French geographic populations: some exhibited signs of recent expansion, while others suggested the presence of ancient populations. Conclusions It is possible that small populations of H. marginatum were already present in France and are now more abundant. This recent change in population structure could be owing to increased human activity and climate change. These factors, combined with a potentially high level of phenotypic plasticity, could facilitate H. marginatum conquest of more northerly latitudes in France and other European countries. Graphical Abstrac
Role of liquid crystal behavior of CNC/PEGDA/collagen suspensions on their orthotropic organization obtained by ultrafiltration and ultrasound
No full textInternational audienceThis study explored the effect of adding biologically relevant macromolecules on the preservation of cellulose nanocrystal (CNC) orthotropic organization already obtained in aqueous media, via the combined action of frontal ultrafiltration (FU) and ultrasound (US). In particular, the effect of a photocurable polymer poly(ethylene glycol) diacrylate (PEGDA) with aqueous CNC suspension, in 80/20 weight ratio [water/PEGDA] and collagen were explored. Rheometric and polarized light microscopy measurements were used to reveal the liquid crystal behavior of suspensions. In situ dichroism during the FU/US process allowed to examine the conservation of orthotropic organization. First, the results have proved that the liquid crystal-like behavior is essential for achieving the desired orthotropic orientation of CNC/PEGDA/Collagen suspensions under FU and US. Second, acoustic power and filtration time have been identified as key parameters in preserving the orthotropic arrangement. Third, specific formulation conditions have been found to successfully achieved the orthotropic structure: i) without collagen, 20 wt% PEGDA and 5 to 8 wt% CNC; and ii) with collagen at acidic pH, 20 wt% PEGDA, 6 to 8 wt% CNC, and 0.01 to 0.1 mg/mL collagen. These findings pave the way for future investigations to produce orthotropic hydrogels for tissue engineering, by combining FU/US process with photocrosslinking
Evaluation of PBK models using the OECD assessment framework taking PFAS as case study
No full textInternational audiencePhysiologically based kinetic (PBK) models are becoming increasingly important in chemical risk assessment, helping in linking external and internal exposure concentrations, thereby supporting the development of regulatory health-based limits for chemicals with exposure from environmental, occupational, and consumer sources. To increase confidence in PBK models for regulatory purposes, the OECD published a guidance document in 2021 outlining the characterization, validation and reporting of PBK models. However, its use remains limited in chemical toxicology as reflected by the few publications that have applied it during model development. The aim of this study was to evaluate several published PBK models for Per- and polyfluoroalkyl substances (PFASs) as proof of concept to assess their validity and credibility for regulatory purposes, based on the OECD guidance. Out of 28 published PFASs human PBK models considered, 11 were selected for evaluation. The assessment used the OECD guidance document, encompassing two main areas: i) documentation (context/implementation, documentation, software implementation, verification, and peer engagement) and ii) assessment of model validity (biological basis, theoretical basis of model equations, input parameter’s reliability, uncertainty and sensitivity analysis, goodness-of-fit and predictivity). To standardize this process, an online evaluation system based on the OECD guidance was developed and used for this model evaluation exercise. The collected data were analysed to assess the overall quality of published models and identify limitations in the current PFAS model landscape. Our analysis revealed opportunities for improvement in the biological representation within current PFAS models, particularly regarding the inclusion of diverse population groups. Currently, PFAS models primarily focus on only four compounds, highlighting an opportunity to extend coverage to other PFASs using read-across approaches for data-poor chemicals. Furthermore, our findings show that a harmonized approach for PBK model reporting is needed. To facilitate broader adoption of the OECD guidance, we developed and hosted an R Shiny template on our group’s web server (https://app.shiny.insilicohub.org/Evaluation_PBPK/). This template can act as valuable tool for researchers evaluating PBK models according to the OECD guidance
Analytical and diagnostic performances of a triplex real-time polymerase chain reaction assay for quantification of Streptococcus suis species, serotypes 2 and 1/2 and serotype 9 in swine biological samples
No full textInternational audienceThe epidemiological control of Streptococcus (S.) suis infections require detection and quantification of the serotypes most frequently implicated in pathological cases (serotypes 2 and 9), and even more so of all serotypes of the bacterial specie directly in pig organs including tonsils. This study developed a new multiplex qPCR assay for the simultaneous quantification of these three targets: S. suis species (all the 29 serotypes), S. suis serotype 2 (and 1/2 indistinguishable by qPCR) and S. suis serotype 9. This qPCR assay based on the recN and cps genes was tested with 84 S. suis strains. The specificity was verified with a collection of 43 strains of bacterial species other than S. suis. The estimated detection thresholds of the recN, cps2J and cps9H targets were 5 (±1), 6 (±2) and 5 (±3) ge/assay, respectively. The amplification efficiencies and correlation coefficients were 99.1 % (±3.1 %) and 0.999 (±0.002), 97.4 % (±2.9 %) and 0.999 (±0.002), 100 % (±3.2 %) and 0.998 (±0.002), respectively. The diagnostic specificity, measured with 74 samples, was 100 %. The diagnostic sensitivity, evaluated from 126 samples, was 98 %. These performances enabled its use to assess tonsillar carriage in a farm with streptococcal infections. S. suis was detected in all tonsils (100 %) whereas S. suis serotypes 2 and 1/2 and S. suis serotype 9 were detected in 38 % and 29 % of 180 samples, with mean amounts at 4.80 (±0.78), 3.26 (±0.69) and 3.27 (±0.60) log(10) ge/ml, respectively. This triplex qPCR assay validated has significant potential for applications in monitoring and controlling this zoonotic pathogen
HVAC filters clogging detection using electrospun sensory membrane
No full textInternational audienceClogged air filters increase pressure drop, thereby raising energy consumption in heating ventilating and air conditioning (HVAC) systems. Monitoring this pressure drop enables real-time detection of clogging. This study focuses on developing a thermoplastic polyurethane (TPU) membrane designed for strain sensing to be used as a pressure drop sensor in ventilation systems. TPU nanofiber membranes were electrospun into a honeycomb structure to minimize the pressure drop caused by the sensor itself, with a carbon sensor ink printed in a zigzag pattern to enable signal detection. Structured collectors with porous honeycomb patterns were used during electrospinning to create these honeycombed membranes. The effect of honeycomb hole size (0.5 cm and 1.5 cm, with corresponding membranes labeled TPU-0.5 and TPU-1.5) on electrical resistance and pressure drop was assessed in a lab-scale ventilation tunnel at various airflow velocities representative of those used in HVAC systems. The TPU-0.5 membrane showed higher sensitivity ( ΔR / R up to 28%) but resulted in a significantly higher-pressure drop compared to the TPU-1.5 membrane (134.3 ± 7.6 Pa vs. 34.0 ± 2.4 Pa at 3.83 m s −1 ). Cyclic testing revealed resistance drift, indicating the need for stabilization cycles to ensure consistent results. The findings indicate that the TPU-1.5 membrane achieves a better balance between sensitivity (10%–15% resistance change at 3.83 m s −1 of velocity) and pressure drop (maximum 32–38 Pa at 3.83 m s −1 of velocity), making it more suitable for real-world applications in air handling units, particularly for monitoring filter clogging