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Impact of breastfeeding on liver metabolic dysfunction in offspring born from hyperglycaemic dams in a rodent model
No full textInternational audienceBackground: Gestational Diabetes Mellitus (GDM) induces lasting metabolic programming in offspring, increasing their risk for insulin resistance and metabolic dysfunction-associated steatotic liver disease (MASLD). MASLD-rising incidence in youth suggests early-life origins, potentially shaped by maternal metabolic status during gestation and lactation, and also breastfeeding and sex-specific factors. Aims: This study investigates how GDM affects maternal transmission of MASLD-risk, focusing on breast milk contribution.Methods: A rodent GDM-model was developed using a high-fat high-sucrose (HFHS) diet to induce impaired glucose tolerance (IGT) limited to gestation (4HFHS) or maintained throughout gestation-lactation (7HFHS), compared to a control-fed euglycemic group (CTL). Cross-fostering at birth allowed to assess the independent impact of gestation versus lactation. Offspring underwent body composition analysis using dual-energy X-ray absorptiometry at postnatal day (PND) 200. Insulin-sensitivity was evaluated at PND 220, through oral glucose tolerance test and euglycemic-hyperinsulinemic clamp following a Western-Diet (WD) challenge (100d). Metabolome (LC-MS) and transcriptome (qRT-PCR) were analyzed in offspring blood and liver.Results: Male GDM-offspring nursed by 7HFHS-dams and WD-fed at adulthood exhibited the highest fat mass and liver weight, compared to other WD-groups or their chow-fed counterparts. This phenotype was associated with disrupted lipid metabolism including incomplete fatty acid oxidation (FAO), increased cholesterol synthesis, reduced polyunsaturated fatty acid synthesis and incorporation in triglycerides or phosphatidylcholines. GDM-offspring nursed by CTL-dams and WD-fed displayed IGT (male) and lower insulin-sensitivity (female), lower FAO, combined with higher hepatic expression of glucose and lipid transporters, and FETUA, an insulin-resistance biomarker. In contrast, GDM-offspring reared by 4HFHS-dams showed improved FAO, reduced gluconeogenesis and lipogenesis (essentially in females), but better insulin receptor and lower FETUA expression. Conclusions: GDM and lactational exposure significantly influence liver metabolic programming in offspring in a sex-specific manner. GDM-related milk components may act as early modulators of MASLD-risk, highlighting breastfeeding as a critical window for potential postnatal intervention
Small extracellular vesicles as biomarkers candidates for moderate asthma of horses: A proteomic investigation
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La biosécurité au quotidien : des mesures simples pour prévenir une épidémie à l'écurie et en compétition
No full textNational audienceLa gestion d’une épidémie repose sur une détection précoce, une communication transparente et la mise en place rapide de mesures de biosécurité adaptées (isolement, traçabilité, contrôle des déplacements). L’exemple de l’épidémie de rhinopneumonie équine à Valence a montré l’importance de la réactivité et de la coordination internationale pour limiter la propagation. Lors des JOP 2024, des protocoles stricts de surveillance sanitaire, de quarantaine et de contrôle ont été appliqués pour sécuriser les chevaux et garantir la continuité des compétitions. Ces expériences soulignent aussi l’importance de la prévention en amont (vaccination, suivi sanitaire rigoureux, préparation logistique) et de la coopération entre organisateurs, responsables de la biosécurité, vétérinaires et autorités sanitaire
Optimization of Injection Strategy for CH4/Diesel Dual-Fuel Engine Using Response Surface Methodology
No full textInternational audienceDual-fuel combustion technology allows for lower emissions of particulate matter (PM) and nitrogen oxide (NOx). However, under low load conditions, this mode of combustion has large amounts of emissions of carbon monoxide (CO) and unburned hydrocarbons (HCs) and low thermal efficiency. Several solutions have been presented to solve the issues associated with this operating mode. Optimizing the injection strategy is a potential method to enhance engine performance and reduce emissions, given that the injection parameters have significant effects on the combustion process. The present investigation optimized a methane/diesel dual-fuel engine’s emissions and performance using response surface methodology (RSM). Three parameters were investigated as input variables: dwell time (DT), diesel pre-injection timing (IT), and engine load (EL). RSM was used to optimize brake thermal efficiency (BTE), NOx emissions, and HC emissions, aiming to identify the best combination of these input factors. The RSM analysis revealed that the optimal combination of input parameters for achieving maximum BTE and minimum NOx and HC emissions is an 87% engine load, an 8° crank angle (CA) dwell time, and a 11° bTDC pre-injection timing. The RSM model demonstrated high accuracy with a prediction error less than 4
Gyroid‐Structured Scaffolds Guide Uniform Ossification and Modulate Vascular Morphology During Rat Calvarial Bone Defect Regeneration
No full textInternational audienceBone repair procedures rely on osteoconductive material scaffolds that guide and promote bone ingrowth through their architecture. This study investigated how the bone formation and vascularization are modulated within gyroid macroporous scaffolds during the regeneration of rat calvarial bone defects. It compared scaffold‐guided regeneration to spontaneous healing through 3D analysis of both ossification and vascularization. Two disc‐shaped bioceramic scaffolds with either wide or narrow porous geometries were designed and fabricated to facilitate or limit bone ingrowth. While overall ossification dynamics were similar regardless of repair efficacy, scaffold presence modulated the ossification pattern, promoting bone formation throughout by conduction. The scaffolds also influenced vascular network morphology but not its density. Notably, 3D imaging revealed a negative correlation between vascularization and bone formation in scaffold‐filled defects, while no correlation was found in empty defects. This result suggests that ossification during calvarial regeneration relies on additional pro‐osteogenic factors beyond robust vascularization. These insights are valuable for optimizing scaffold‐based strategies to enhance bone regeneration in calvarial defects
Effects of Pregnancy and Lactation on Bone Microstructure and Material Properties in a Rat Model of Bariatric Surgery
No full textInternational audienceObesity is a major public health issue worldwide. Despite various approaches to weight loss, the most effective technique for reducing obesity, as well as diabetes and associated diseases, is bariatric surgery. Increasingly, young women without children are undergoing bariatric surgery, vertical sleeve gastrectomy (VSG) being the most common procedure nowadays. However, despite several reports suggesting bone loss after VSG, little is known about the potential additive effects of gestation and lactation after VSG to bone health. This study investigated the combined effects of pre-gestational VSG and subsequent gestation/lactation on bone metabolism in a rat model fed a high fat high sugar (HFHS) diet, with a focus on bone biomechanics, mass, microarchitecture and material properties. Furthermore, bone mass and remodelling were followed longitudinally by microCT prior to surgery, 4 weeks post-surgery, after weaning and at sacrifice. Significant alterations in bone mass and microarchitecture, characterized by changes in trabecular thickness and number, as well as changes in bone formation and resorption were influenced by both surgery and reproductive demands. Mechanical testing at sacrifice demonstrated compromised long bone fragility, in rat with HFHS regardless of the surgical procedure (Sham or VSG). Furthermore, analysis of bone material properties highlighted potential disruptions in the pattern of bone mineralization in sham and VSG animals fed a HFHS diet. These findings underscore the complex interplay between pre-gestational VSG and subsequent gestation/ lactation in modulating bone metabolism in the investigated rat model. The preclinical rat model may help with optimizing surgical strategies and developing targeted interventions to mitigate potential bone-related complications associated with VSG in reproductive-aged individuals
Gestion de l'analgésie PER et POST opératoire immédiate chez la chienne lors de césarienne : étude comparative par réalisation d'infiltration traçante de lidocaïne ou de bupivacaïne au niveau de la ligne d'incision cutanée
No full textLa gestion de la douleur en médecine vétérinaire, notamment en chirurgie, a connu des progrès notables ces dernières années. La césarienne chez la chienne pose des défis spécifiques en matière d’anesthésie et d’analgésie, tant pour le bien-être de la mère que pour la survie et la vitalité des nouveau-nés. Les deux premières parties de cette thèse s’appuient sur une étude bibliographique approfondie traitant de la physiologie de la gestation et de la mise bas, des complications, et de la césarienne ainsi que les fondements physiologiques et pharmacologiques de l’anesthésie et de l’analgésie dans un contexte de césarienne selon la littérature actuelle. Cette étude compare l’efficacité de deux anesthésiques locaux, la lidocaïne (L) et la bupivacaïne (B), administrés par infiltration traçante au niveau de la ligne d’incision cutanée. Menée sur 21 chiennes gestantes au CHUV d’Oniris (2023–2025), elle repose sur un protocole randomisé, mené en double aveugle. Les effets analgésiques ont été évalués via des paramètres physiologiques et comportementaux en per et post-opératoire. Un total de 101 fœtus a été diagnostiqué ; 100 chiots sont nés vivants et un était mort-né. Huit chiots sont décédés dans les trois jours suivant la naissance (taux de mortalité : 0,09 %). Les analyses statistiques (LMM, GLMM) révèlent une meilleure stabilité peropératoire de la fréquence cardiaque, de la fréquence respiratoire et de la pression artérielle systolique dans les groupes L et B que dans le groupe témoin. Les scores de douleur postopératoire étaient significativement plus bas dans les groupes L et B durant les 30 premières minutes (p < 0,05, test de Kruskal–Wallis). Aucune différence significative n’a été observée entre les groupes au jour 3 (p > 0,05). L’infiltration traçante de lidocaïne ou de bupivacaïne a amélioré le confort postopératoire immédiat et soutient leur utilisation dans les protocoles d’analgésie multimodale pour les césariennes
Unveiling the Metabolic Impact of Growth Hormone in Dairy Cows: An Integrated Metabolomics Analysis of Milk and Urine
No full textInternational audienceRecombinant bovine growth hormone (rbGH) is a synthetic analogue of natural somatotropin, used to promote growth and milk production in dairy cattle. While permitted in certain countries, its use is strictly prohibited in Europe due to animal welfare and consumer safety concerns. Consequently, reliable analytical methods-such as immunoassays and liquid chromatography-tandem mass spectrometry (LC-MS/MS)-are essential for monitoring its illicit use.In this study, urine and milk samples were collected from cows treated with rbGH at multiple time points, up to 219 days after initial administration. A longitudinal analysis was conducted using advanced metabolomics and lipidomics approaches based on liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS). This untargeted strategy enabled the detection of subtle and time-resolved molecular changes associatedwith hormonal exposure. Urine analysis revealed comprehensive metabolic alterations, while lipidomics profiling of milk highlighted dynamic shifts in lipid composition over time. To further elucidate the biological impact of rbGH, the most discriminant molecular features were subjected to targeted fragmentation (PRM) on an orthogonal mass spectrometry platform, providing structural information and aiding in the identification of affected metabolic pathways.By leveraging state-of-the-art LC-HRMS technologies, this work provides valuable insights into the systemic effects of rbGH and supports the discovery of novel, yet-to-be-identified molecular biomarkers for improved monitoring. These findings enhance the analytical toolbox available for regulatory surveillance and contribute to a deeper understanding of the biological impact of rbGH administration in livestock
MultANOVA Followed by Post Hoc Analyses for Designed High‐Dimensional Data: A Comprehensive Framework That Outperforms ASCA, rMANOVA, and VASCA
No full textInternational audienceABSTRACT Analytical platforms generate high‐dimensional data, where the number of variables usually exceeds the number of observations. Such data are frequently derived from an experimental design, where samples have been collected to identify potential variation in the factors or interactions of interest. To circumvent issues related to large data sizes when evaluating factor and interaction effects, ANOVA simultaneous component analysis (ASCA), regularized multivariate analysis of variance (rMANOVA), and variable selection ASCA (VASCA) have been proposed previously. However, they require computationally intensive methods to test the effects of factors and interactions. In the present paper, multiple ANOVAs (MultANOVA) is proposed as a simple yet effective alternative to the above methods. MultANOVA has the advantage of being direct and fast, as it does not rely on intensive calculation methods, while incorporating a variable selection strategy. This method entails the execution of multiple ANOVAs, one per variable, with multiple test corrections. Subsequent post hoc analyses are also introduced. These encompass multiple least‐squares difference tests (MultLSD) for the pairwise comparison of multivariate least‐squares means and diagonal canonical discriminant analysis (DCDA) with approximate confidence ellipses to visualize significant effects. MultANOVA is compared to the aforementioned methods based on simulations, which demonstrate that it holds the nominal alpha risk as opposed to rMANOVA and VASCA, while being more powerful than ASCA and VASCA. Even though MultANOVA is proven less powerful than VASCA for variable selection, it has been demonstrated to hold the nominal risk, whereas VASCA does not. Finally, the MultANOVA framework is illustrated based on metagenomics, metabolomics, and spectroscopic data