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Relations entre signes cliniques, anomalies échographiques et lésions pulmonaires à l'autopsie chez des bovins âgés de moins de 2 ans et référés dans les écoles vétérinaires de Nantes et de Toulouse
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Microplastiques dans les sédiments fluviaux : une importante hétérogénéité à l’échelle de la bande de sédimentation active
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Epidemiological and Clinical Profile of Methicillin-Resistant Staphylococcus aureus (MRSA) Infections in European Hedgehogs (Erinaceus europaeus) Treated at a Wildlife Health Center in Northwestern France
International audienceThe European hedgehog (Erinaceus europaeus) is commonly observed in France, residing near human facilities, and is the most frequently treated mammal species in wildlife rehabilitation centers. Consequently, contacts with humans can lead to the potential transmission of bacteria, such as Staphylococcus aureus, between species. Although the presence of S. aureus, particularly methicillin-resistant S. aureus (MRSA), has been documented in hedgehogs across Europe, the situation in France remains unclear. We assessed 139 hedgehogs representative of those typically admitted to our Wildlife Health Center. Carriage of MRSA was determined, and MRSA-positive individuals were characterized clinically and epidemiologically to identify potential risk factors of MRSA carriage. We found an 18% MRSA carriage rate, with 76% of the strains exhibiting the mecC resistance gene. Adult males constituted 60% of the MRSA-positive cases, predominantly found in spring and displaying skin lesions, particularly “dirty wounds.” Multivariate logistic regression identified “age”, “sex”, “human density”, “dirty wounds”, and “respiratory troubles” as significantly associated with MRSA carriage in these hedgehogs. Our study establishes a foundation for improved monitoring of health conditions in French hedgehogs and their MRSA carriage, offering new insights for enhancing biosecurity measures in wildlife rehabilitation centers by pinpointing high-risk individuals
Abstract 6494: Genetically characterized canine tumoral cell lines are relevant models to test the efficacy of new targeted therapies: Example of anti-MDM2 targeted therapy
International audienceGenetic characterization of cell lines is essential for understanding and predicting sensitivity to anti-tumoral targeted therapies. This study develops a panel of genetically characterized tumoral cell lines to test novel and repositioned anti-tumor therapies, focusing on canine mucosal melanoma (MM) and histiocytic sarcoma (HS) models. We established a diverse panel of MM and HS canine cell lines, leveraging the strong genetic and clinical similarities between canine and human cancers. Using long-read sequencing (Nanopore) technology, we performed comprehensive genetic characterization, identifying single nucleotide variants, structural variations, and copy number alterations. RNA sequencing complemented our genomic analysis by assessing gene expression profiles and potential fusion transcripts. Our methodology involved several key steps:1. Cell line establishment from tumor samples2. Comprehensive genetic profiling3. In vitro drug sensitivity screening4. In vivo validation through mouse xenograft modelsAs a proof of concept, we evaluated Idasanutlin, an MDM2 inhibitor, across our developed cell lines. Our findings demonstrated a clear correlation between TP53 status and drug sensitivity: cell lines with wild-type TP53 were sensitive to the drug, while those with mutated TP53 showed resistance. This result underscores the potential of genetic profiling to guide treatment decisions. The unique value of our approach lies in its ability to:· Identify biomarkers of drug response· Elucidate resistance mechanisms · Discover treatment-responsive subgroups based on genetic profile in previously untreated cancer· Inform the potential of new or repositioned targeted therapiesCanine cancer models offer distinct advantages, including:· Higher incidence of rare cancers in specific breeds· Genetic predispositions from selective breeding· Closer genetic and clinical similarity to human cancersOur cell line panel provides a systematic approach to validate therapeutic strategies tailored to specific genetic contexts. By integrating genomic, transcriptomic, and drug sensitivity data, we create a powerful research tool for both veterinary and human oncology. The research demonstrates the potential of comparative oncology in advancing cancer treatment. Our genetically characterized cell lines offer a comprehensive platform for drug screening and biomarker discovery, ultimately aiming to improve patient care and survival rates for challenging cancers. This work represents a significant step towards more personalized and precise cancer therapies, bridging the gap between preclinical research and clinical application
Benefits of using immersive virtual reality in haptic dental simulation for endodontic access cavity training: A comparative crossover study: Impact of immersive virtual reality on haptic dental simulation for endodontic access cavity training
International audienceIntroduction The use of haptic virtual reality simulators in preclinical dental education is evolving rapidly. However, the application of immersive haptic simulations for specific dental procedures, such as access cavity preparation, has not been extensively explored. Aims This study aimed to (i) evaluate the impact of using the VirTeaSy Dental® simulator in conjunction with a virtual reality (VR) headset on student performance during access cavity preparation, with a focus on haptic parameters; (ii) assess students' perceptions of the experience; and (iii) examine the side effects associated with VR headset use. Methodology The study included 90 third‐year dental students from the Dental Faculty of Nantes University, enrolled in January 2023. Participants were divided into two parallel groups. In Phase 1, Group 1 ( n = 45) completed two endodontic access cavity exercises on the VirTeaSy Dental® without the VR headset, whilst Group 2 performed the same exercises using the VR headset. In Phase 2, the groups switched conditions and followed the same protocol. Performance was assessed using haptic parameters, and comparisons between groups for each phase were made using parametric and non‐parametric tests ( p < .05). Students also completed questionnaires to assess their experience and report any side effects from using the VR headset. Results Across both groups and phases, participants performed better in access cavity preparation without the VR headset. They showed greater accuracy, made fewer errors, and completed the exercises more quickly. Notably, more students failed to complete the exercises within the 10‐minute time limit when using the VR headset (27 vs. 12 in Group 1, 23 vs. 13 in Group 2). Most participants expressed a preference for using VirTeaSy Dental® without the VR headset. Approximately, 20% of students reported side effects, including dizziness, nausea, migraines, and neck muscle fatigue. Conclusion The results suggest that full immersion in haptic simulation, when paired with a VR headset, negatively impacts student performance in complex tasks such as access cavity preparation. These findings underscore the current limitations of immersive virtual reality in dental education and highlight the need for technical refinements before its widespread adoption in preclinical training
Three-step scalable production of extracellular vesicles from pancreatic beta cells in stirred tank bioreactors promotes cell maturation and release of ectosomes with preserved immunomodulatory properties
International audienceSmall extracellular vesicles (sEV) released by healthy beta cells are promising candidates for diabetes therapy thanks to their aptitude to modulate inflammation, to induce or maintain pancreatic function and to prevent pathogenic mechanisms. To advance the clinical development of therapeutics, there is a crucial need for scalable production methods. Stirred tank bioreactors (STR) are widely used in the industry due to their ability to provide homogeneous gas and nutrient supply, online monitoring, and efficient scale up. Anchoragedependent cells can be cultured in STR on microcarriers or as spheroids, but may experience shear stress, which can affect sEV phenotype and function. Using pancreatic beta cells, this study identifies critical cell culturing parameters, including culture mode (monolayer vs. spheroids), medium formulation (with or without serum, glucose control), and process parameters (stirring, duration, cell density). The findings show that small spheroid culture promotes beta cell maturation without decreasing the yield of sEV per cell, despite a reduced cell surface exchange area. However, stirring increased expression of cellular stress markers and decreased cell viability. Set up of a three-step bioprocess allowed to maximize cell viability and sEV yields at high cell density over short production duration. sEV produced under these conditions maintained high purity, membrane integrity, and the aptitude to reduce Tlymphocyte proliferation and IFN-γ cytokine secretion in a mixed lymphocyte reaction. Flow cytometry analysis revealed lower CD63/CD81 ratios in STR, indicating enhanced ectosome production. Switch from high glucose expansion to low glucose production medium further allowed to direct sorting of the antigen insulin into beta-sEV. This study demonstrates the feasibility of producing functional sEV from mature beta cells cultured as small spheroids, suitable for upscale. Production of sEV in STR may be particularly beneficial for ectosomeenriched compound loading for therapeutic applications.</div
Probing the colloidal behavior of a cell wall polysaccharides-degrading enzyme in a highly constrained model system
International audienceUnderstanding the specific interaction of cell wall polysaccharides degrading-enzymes with their substrates is of fundamental and practical interest for the fine grasp of their activity. Such interactions are difficult to unveil in real-life conditions due to the structural complexity of the plant cell wall. In this work, we present complex and highly confined model systems of cholesteric cellulose nanocrystal suspensions reaching dimensions close to those found in the plant cell wall. Cellulose-xyloglucan (XG) assemblies of various surface chemistries were studied, allowing to probe the interactions and diffusion behavior of a glucanase both in diluted dynamic conditions and in an organized and concentrated (110–140 g/L) cholesteric environment. QCM-D and synchrotron source-deep UV analyses showed that XG adsorbed in a flat and extended conformation changed the glucanase interaction with the polysaccharides from attractive to repulsive, making it prone to spontaneously migrate to regions with lower solid content. Furthermore, it strongly increased the enzyme diffusion kinetics. Our results confirm the preferential interaction of both enzyme and XG on the cellulose hydrophobic crystalline plane. This work provides new insights on the influence of the interaction of a protein with a substrate on its transport in a constrained environment
Modeling Geobacillus stearothermophilus spores inactivation in plant-based drinks to design UHT processing
International audienceThis study provides predictive models for G. stearothermophilus spores inactivation in four plant-based drinks, half-skimmed bovine milk and Brain Heart Infusion (BHI) broth and while also evaluating of matrix effect on inactivation. Heat inactivation was performed using the capillary tube method within the temperature range 115-127 °C. Geeraerd's model - which incorporates initial level, shoulder duration, inactivation rate and tailing - was fitted to the data. Secondary models were developed on the logarithm of the D-values with validation at 130 °C. The ZT values in the different matrices ranged between 7.93-9.98 °C and log10D121°C between 0.43-0.55. Statistical tests revealed no significant differences among the plant-based drinks enabling a general model for the four of them. However, the heat resistance was significantly higher in the bovine milk compared to plant-based drinks. The time to achieve a 5-log reduction under a UHT regime, was different, ranging from 4.28 s to 10.08 s at 140 °C for the six matrices. These differences indicate the importance of considering the food matrix in thermal processing. The findings of this study provide insights on designing thermal processes and support the development of data-driven risk assessments for these products
Workflow4Metabolomics (W4M): A User-Friendly Metabolomics Platform for Analysis of Mass Spectrometry and Nuclear Magnetic Resonance Data
International audienceVarious spectrometric methods can be used to conduct metabolomics studies. Nuclear magnetic resonance (NMR) or mass spectrometry (MS) coupled with separation methods, such as liquid or gas chromatography (LC and GC, respectively), are the most commonly used techniques. Once the raw data have been obtained, the real challenge lies in the bioinformatics required to conduct: (i) data processing (including preprocessing, normalization, and quality control); (ii) statistical analysis for comparative studies (such as univariate and multivariate analyses, including PCA or PLS-DA/OPLS-DA); (iii) annotation of the metabolites of interest; and (iv) interpretation of the relationships between key metabolites and the relevant phenotypes or scientific questions to be addressed. Here, we will introduce and detail a stepwise protocol for use of the Workflow4Metabolomics platform (W4M), which provides user-friendly access to workflows for processing of LC-MS, GC-MS, and NMR data. Those modular and extensible workflows are composed of existing standalone components (e.g., XCMS and CAMERA packages) as well as a suite of complementary W4M-implemented modules. This tool suite is accessible worldwide through a web interface and is hosted on UseGalaxy France. The extensible Virtual Research Environment (VRE) provided offers pre-configured workflows for metabolomics communities (platforms, end users, etc.), as well as possibilities for sharing among users. By providing a consistent ecosystem of tools and workflows through Galaxy, W4M makes it possible to process MS and NMR data from hundreds of samples using an ordinary personal computer, after step-by-step workflow optimization. (c) 2025 Wiley Periodicals LLC.Basic Protocol 1: W4M account creation, working history preparation, and data uploadSupport Protocol 1: How to prepare an NMR zip fileSupport Protocol 2: How to convert MS data from proprietary format to open formatSupport Protocol 3: How to get help with W4M (IFB forum) and how to report a problem on the GitHub repositoryBasic Protocol 2: LC-MS data processingAlternate Protocol 1: GC-MS data processingAlternate Protocol 2: NMR data processingBasic Protocol 3: Statistical analysisBasic Protocol 4: Annotation of metabolites from LC-MS dataAlternate Protocol 3: Annotation of metabolites from NMR dat
The clinical value and most informative threshold of polygenic risk score in the Quebec City Case-Control Asthma Cohort
International audienceGenome-wide association studies (GWAS) have identified genetic variants robustly associated with asthma. A potential near-term clinical application is to calculate polygenic risk score (PRS) to improve disease risk prediction. The value of PRS, as part of numerous multi-source variables used to define asthma, remains unclear. This study aims to evaluate PRS and define most informative thresholds in relation to conventional clinical and physiological criteria of asthma using a multivariate statistical method. Clinical and genome-wide genotyping data were obtained from the Quebec City Case-Control Asthma Cohort (QCCCAC), which is an independent cohort from previous GWAS. PRS was derived using LDpred2 and integrated with other asthma phenotypes by means of Principal Component Analysis with Optimal Scaling (PCAOS). PRS was considered using 'ordinal level of scaling' to account for non-linear information. In two dimensional PCAOS space, the first component delineated individuals with and without asthma, whereas the severity of asthma was discerned on the second component. The positioning of high vs. low PRS in this space matched the presence and absence of airway hyperresponsiveness, showing that PRS delineated cases and controls at the same extent as a positive bronchial challenge test. The top 10% and the bottom 5% of the PRS were the most informative thresholds to define individuals at high and low genetic risk of asthma in this cohort. PRS used in a multivariate method offers a decision-making space similar to hyperresponsiveness in this cohort and highlights the most informative and asymmetrical thresholds to define high and low genetic risk of asthma