HAL ENVT (Ecole Nationale Vétérinaire de Toulouse)
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    R-scripts for rabbit coprophagous behavior website

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    R-scripts used to analyse the data presented in the article "Coprophagia early in life tunes immune system gene expression in ileum after weaning in rabbit", Cauquil L., Beaumont M., Schmaltz-Panneau B., Liaubet L., Lippi Y., Bluy L., Poli M., Gress L., Lencina C. , Duranthon V., Combes S

    Contemporary neoadjuvant strategies for rectal cancer: The GRECCAR snapshot study

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    International audienceAim Neoadjuvant treatment for rectal cancer has evolved markedly with the growing adoption of total neoadjuvant therapy ( TNT ), organ‐preservation strategies and selective omission of radiotherapy. Recent trials support risk‐based personalization, but its application in real‐world settings remains poorly documented. The aim was to describe current neoadjuvant treatment practices for mid‐low rectal cancer in French expert centres and identify tumour‐ and patient‐related factors influencing decisions. Method This observational study included patients with non‐metastatic rectal adenocarcinoma ≤10 cm from the anal verge, discussed in tumour boards (October 2022 to March 2023) across GRECCAR centres. Tumours were classified as early, intermediate‐risk or locally advanced rectal cancer (LARC). Neoadjuvant treatments were analysed according to tumour extension, location and age. Results Among 463 patients from 27 centres, the most frequent regimen was induction chemotherapy, mainly FOLFIRINOX, followed by long‐course chemoradiotherapy (CRT) (65%). This approach was used in 51%, 66% and 71% of patients in the early, intermediate‐risk and LARC groups, respectively ( p = 0.0060). TNT was more frequently administered for low‐ than mid‐rectal cancers, especially in LARC (86% vs. 71%, p = 0.016). In patients >75 years, CRT + consolidation chemotherapy and radiotherapy alone were proportionally more frequent. Among the early rectal cancers, those treated with induction chemotherapy + CRT had more advanced features than those treated with CRT alone (cT3: 80% vs. 43%, cN+: 62% vs. 10%, tumour size: 3.4 vs. 2.3 cm; all p < 0.001). Conclusion TNT with induction chemotherapy is the predominant neoadjuvant approach in French expert centres. Tumour classification, location and patient age significantly influence treatment choices, reflecting a shift towards personalized context‐specific care

    Assessing methane production and feed efficiency in both growing and mature ovine animals in six countries across Europe, South America and Oceania

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    International audienceUnderstanding key animal performance and nuisance factors associated with methane (CH 4 ) output and feed intake is crucial in developing greenhouse gas mitigation strategies and incorporating these traits into international sheep breeding goals. The objectives of the current study were to: 1) investigate animal and nuisance (environmental + management) factors associated with CH 4 output and feed intake; and 2) determine relationships between CH 4 output and feed efficiency in sheep and whether or not they differ by country. Methane output was measured in sheep in Ireland, Norway, New Zealand (NZ) and Uruguay using portable accumulation chambers (PAC), and in France using GreenFeed technology. Individual feed intake was quantified using various techniques across six countries (Ireland, United Kingdom, Norway, France, Uruguay, NZ), on sheep housed indoors, grazing outdoors, and consuming forage or a total mixed ration. Studies varied by sheep breed and age, as well as feed types and measurement methods; factors associated with the variability in CH 4 output and feed intake therefore differed by country. Despite variation between studies, phenotypic relationships among CH 4 , carbon dioxide (CO 2 ), feed intake, feed efficiency, and live weight, were broadly similar across countries. Correlations with CH 4 output (g/d) were consistent and moderate with live weight (r = 0.41-0.55); variable with dry matter intake (DMI), ranging from 0.24 (France) to 0.88 (Norway); and consistently weak with residual feed intake (RFI). Correlations with CO 2 output (g/d) were consistent with live weight gain (r = 0.57) where estimated (France, Uruguay); variable with DMI, from moderate (r = 0.48 for France to r = 0.54 for NZ) to high (r = 0.71, Uruguay); and weak (r = 0.12, Uruguay) to moderately weak (r = 0.21, France) with RFI. Despite disparate datasets, combining data facilitates comparison and discussion on methodologies and interpretation of results. Results support the hypothesis that specific biological processes govern some trait relationships, being independent of factors like breed, age and feed, but that other relationships (e.g. between CO 2 and feed intake) are potentially strongly influenced by methodology and warrant further investigation. This is pertinent as we seek feed intake proxies to allow the estimation of CH 4 yield, an important metric in international CH 4 accounting

    Feed restriction has no effect on milk lipolysis, although it results in a marked reduction in milk lipoprotein lipase activity in dairy goats

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    International audienceClimate change pressures livestock feeding systems by reducing the availability and nutritional quality of forages and pasture. Previous studies have shown that dietary restriction impacts milk lipolysis (i.e. the hydrolysis of milk fat by lipoprotein lipase (LPL)) in cows and ewes. However, data regarding the effects of feed restriction on milk lipolysis in goats are scarce. Therefore, the present study aims to investigate the impact of feed restriction on goat milk composition, with a specific focus on lipolysis, LPL activity and milk fat characteristics. For that purpose, two groups of 12 dairy goats (121 ± 7 days in milk) balanced with regard to the αs1-casein (CSN1S1) genotype (7 A/A goats, corresponding to strong CSN1S1 genotypes and 5 O/O goats, corresponding to null CSN1S1 genotypes) received either a control diet (100 % of the dry matter intake (DMI) ad libitum: non-restricted; NR) or the experimental diet (65 % of the DMI ad libitum: restricted; R) according to a 2 × 2 cross-over design. Dietary restriction did not significantly affect either lipolysis levels in milk or milk fat globule size, whereas a sharp decrease was observed in milk LPL activity within the short-term restriction window tested. A genotype effect was evidenced for milk lipolysis (copper soap method), milk fat content and milk fat yield. No genotype × diet effect was observed with regard to lipolysis or LPL activity under feed restriction. This work provides a solid framework for follow-up lipidomic and proteomic studies to gain a comprehensive understanding of the regulation of the lipolytic system in goats

    Nontuberculous Mycobacterial Lymphadenitis in Children: A French Retrospective Multicenter Study on Epidemiology, Management Strategy and Outcome Over the Last Decade

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    International audienceBackground: Nontuberculous mycobacterial (NTM) adenitis is increasingly recognized in children; however, optimal management strategies remain debated. The aim of this study was to describe the clinical characteristics, management and outcomes of pediatric NTM lymphadenitis in France. Methods: We conducted a multicenter retrospective descriptive study of culture-confirmed NTM lymphadenitis cases in children across 15 French hospitals participating in the MYCOMED network between 2010 and 2019. Results: A total of 279 patients were included, with a progressive increase in diagnoses over the study period, from 11 cases in 2010 to 33 in 2019, with peaks of 38 observed in 2015 and 2018. Most patients were female (64%) with a median age of 3 years. Mycobacterium avium was the most frequently isolated species (71%). Histologic examination revealed necrotizing granulomatous lymphadenitis in two-third of cases (71%, 112/115), and acid-fast bacilli staining was positive in 24.6% (68/276) of the cases. Of the 250 patients with available therapeutic data, 34.8% were treated with surgery alone, 24.8% with antibiotics alone, 28% with combined therapy and 12.4% received no treatment. Overall, 104 children were lost to follow-up. Among 175 patients with follow-up data, the overall cure rate was 96%, with no significant differences between therapeutic strategies. Relapse occurred in 6 children (3.4%). No cases of facial nerve palsy were reported; however, cosmetic sequelae related to scarring were observed. Conclusions: The incidence of pediatric NTM adenitis has increased over the last decade in France, with M. avium as the predominant species. The clinical outcome was favorable in most cases, irrespective of the management strategy. Surgery with complete excision should be considered when technically feasible and safe, while antibiotics or a “wait and see” strategy remain acceptable alternatives

    Moving beyond metrics: Capturing the clinical context behind antibiotic prescriptions in French broiler production

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    International audienceSignificant reductions in antimicrobial use (AMU) in food production animals have been observed over the last10 years across Europe. We sought to understand recent changes in AMU by characterising antibiotic prescribingpatterns in poultry production in the context of associated clinical information. We analysed trends in AMU forconventional broiler chicken production in France based on a dataset of 193,526 sales for 33,831 flocks on 2120farms for 2015–2023, including 21,218 antibiotic prescriptions. We found the percentage of flocks prescribedantibiotics dropped from 65 % in 2013 to 20 % in 2023, plateauing in 2020–2023 (oscillating between 13 % and23 %), and observed a reduction in the use of critical antibiotics. A multiple correspondence analysis and hierarchicalclustering on principal components of 1112 antibiotic prescriptions and associated clinical data for2021–2022 produced 1940 prescription events, grouped in five clusters of antibiotic prescribing patterns, eachcharacterised by a combination of clinical indicators related to age at treatment, lesions, syndromes, diagnoses,and isolated bacteria. Two main clusters were associated with bacterial diagnoses, suggesting that use of antibioticsin these clusters was necessary to manage disease. Two clusters were identified as potential targets forfurther interventions to improve antimicrobial stewardship, focusing on underlying factors driving AMU ratherthan outright reductions. Our findings raise questions about the sustainability of further reductions in AMU andtheir implications for animal health and welfare. This calls for a shift to a more sustainable approach to monitoringantimicrobial stewardship, using integrated indicators which consider AMU within its broader context

    Variability and uncertainty of data from genotoxicity Test Guidelines: What we know and why it matters

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    International audienceThis review comprehensively examines the variability and uncertainty associated with test guideline (TG)-conform genotoxicity data and explores the respective implications for the integration of non-animal-methods (NAMs) into regulatory frameworks. Historical amendments to OECD TGs are mapped to reveal the method’s evolution that improves the scientific quality of the data but also explains data heterogeneity within available databases. An analysis of the major genotoxicity databases ECVAM, ISSMIC, and OASIS demonstrates substantial variability in genotoxicity calls. Using the EFSA genotoxicity database, which currently harbours the best-curated (meta-) data, we estimate that 22–77% of compounds exhibit similarity of replicate results below 85%, depending on the assay. The potentially most important variables statistically explaining variability and sensitivity were analysed. The practical limitations to identify them with high reliability and to define their optimum needs to be accepted as a qualitative baseline uncertainty. These findings underscore the necessity of contextualizing NAM performance evaluations within the intrinsic variability and uncertainty of animal and in vitro reference data. We propose that this variability is explicitly considered in the development and validation of NAM-based Integrated Approaches for Testing and Assessment (IATAs). This review provides a critical foundation for regulators and scientists aiming to enhance the acceptance and utility of NAMs in genotoxicity assessment

    Trajectoire de vieillissement chez le chien : exploration biologique et évaluation d'une solution nutritionnelle

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    With the increase in canine life expectancy, aging has become a central challenge in veterinary medicine. However, the concept of healthy lifespan in dogs remains underexplored, and tools for the early detection of frailty or the prevention of functional decline are still limited. In this context, the present thesis aims to improve the understanding of the biological, clinical, and behavioral mechanisms of canine aging, and to explore potential avenues for preserving its quality.This work is based on a multidisciplinary approach, combining a literature review, a longitudinal clinical study in a cohort of large-breed senior dogs (≥ 8 years, ≥ 20 kg), omics analyses (metabolomics and microbiomics), and the evaluation of the effect of a nutritional solution enriched with antioxidants and microbial derivatives.Our results highlight age-related differences at the metabolic level (decreased methionine, glycine, isoleucine), immune level, inflammation, and gut microbiota composition, suggesting a role of oxidative stress and insulin resistance in the aging process. The concept of canine frailty is defined, validated, and correlated with an unfavorable clinical trajectory (increased pain, higher geriatric score, and cognitive decline). Behavioral traits such as neuroticism, extraversion, and time since adoption are identified as predictive factors of frailty risk.The tested nutritional solution showed a moderate beneficial effect in dogs that were robust at inclusion, particularly on the evolution of alkaline phosphatase and certain circulating amino acids, without detectable effects on the fecal microbiota.A proposal for quadrimestrial clinical monitoring is formulated, integrating the frailty phenotype, selected biological markers, and standardized behavioral tools.This work contributes to laying the foundations of a preventive veterinary geriatric medicine, centered on the early detection of vulnerabilities and the personalization of interventions. It opens concrete perspectives for both veterinary practice and research, particularly regarding the development of targeted nutritional strategies and the validation of functional assessment tools adapted to senior dogs.Avec l’augmentation de l’espérance de vie des chiens, le vieillissement est devenu un enjeu central de la médecine vétérinaire. Pourtant, la durée de vie en bonne santé des chiens reste peu étudiée, et les outils permettant de détecter précocement la fragilité ou de prévenir le déclin fonctionnel sont encore limités. Dans ce contexte, cette thèse vise à mieux comprendre les mécanismes biologiques, cliniques et comportementaux du vieillissement canin, et à explorer les leviers d’action permettant d’en préserver la qualité.Ce travail s’appuie sur une approche multidisciplinaire, intégrant une étude bibliographique, une étude clinique longitudinale sur une cohorte de chiens séniors de grand gabarit (≥ 8 ans, ≥ 20 kg), des analyses omiques (métabolomiques et microbiotiques), et l’évaluation de l’effet d’une solution nutritionnelle enrichie en antioxydants et dérivés microbiens.Nos résultats mettent en évidence des différences liées à l’âge sur le plan métabolique (diminution de la méthionine, glycine, isoleucine), immunitaire, inflammatoire, et du microbiote intestinal, suggérant un rôle du stress oxydant et de la résistance à l’insuline dans le vieillissement. Le concept de fragilité canine est défini, validé, et corrélé à une trajectoire clinique défavorable (augmentation de la douleur, du score gériatrique, et du déclin cognitif). Des variables comportementales comme le névrosisme, l’extraversion ou la durée depuis l’adoption sont identifiées comme facteurs prédictifs du risque de fragilité.La solution nutritionnelle testée montre un effet bénéfique modéré chez les chiens robustes à l’inclusion, en particulier sur l’évolution des phosphatases alcalines et certains acides aminés circulants, sans effet détectable sur le microbiote fécal.Une proposition de suivi clinique quadrimestriel est formulée, incluant le phénotype de fragilité, des marqueurs biologiques ciblés et des outils comportementaux standardisés.Ce travail contribue à fonder une médecine gériatrique vétérinaire préventive, axée sur la détection anticipée des vulnérabilités et la personnalisation des interventions. Il ouvre des perspectives concrètes pour la pratique vétérinaire et pour la recherche, notamment sur la mise au point de stratégies nutritionnelles ciblées et la validation d’outils d’évaluation fonctionnelle adaptés au chien âgé

    Metabolomic analysis of the endometrium of Large White and Meishan pigs reveals differences in biological processes during late gestation

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    International audienceIn pigs, genetic progress has led to an increase in perinatal mortality, mainly due to reduced piglet maturity. The end of gestation (90-110 days of gestation) plays a decisive role in the acquisition of fetal maturity. The endometrium is crucial for its acquisition as it provides nutrients to the fetus through the placenta. The aim of this study is to describe part of the metabolism of the endometrium in late pregnancy and in relation with neonatal survival. For this purpose, we performed untargeted metabolomic measurements by 1H nuclear magnetic resonance and gas chromatography coupled to a flame-ionization detector on 224 endometrial samples and compared the two days of the end of gestation (D90-D110, term at 114 days) and two maternal breeds with contrasted birth survival: Large White (LW, higher birth mortality) and Meishan (MS, lower birth mortality). ResultsOut of the 191 metabolites available in the ASICS package reference library, 46 metabolites and nine neutral lipids were quantified in the endometrial samples. Twenty-two metabolites showed a significant differential abundance in the endometrium between 90 and 110 days of gestation. These differences highlighted a decrease in the amount of glucogenic amino acids such as aspartate, glutamate, and glutamine at D110, indicating a depletion of energy resources in the endometrium. As a result of hypoxic catabolism to maintain energy levels, hypoxanthine and succinate accumulated, possibly contributing to the regulation of hypoxia, ROS and modulation of inflammation of the endometrium during late pregnancy. The study also documented ten endometrial metabolites with a significant differential abundance between LW and MS sows. Glutathione metabolism metabolites showed a decreased abundance in LW, which may contribute to increased oxidative stress. Furthermore, the accumulation of glutamine and phenylalanine may be a possible response to lower amino acid availability in LW, inducing more cellular autophagy and lower maternal immune tolerance in LW endometrium compared to MS.</div

    Microbiota-Host interactions during juvenile growth: exploration of interconnected metabolic networks

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    International audienceThe gut microbiota influences animal growth in various nutritional environments. Despite recent progress, the molecular mechanisms behind this mutualism remain poorly understood. This is partly due to the complexity of the gut microbiota, mainly composed of bacteria, which form intricate nutritional and metabolic networks among themselves and with the host. Given this complexity, no study has yet determined to what extent and how the microbiota's metabolic activities contribute to the host's juvenile growth. The aim of Mi-croMetabo project, is to identify metabolic networks of the gut microbiota and determine how it influences the availability and allocation of the host's metabolic resources during juvenile growth, taking Drosophila melanogaster larva as host model. To do this, we are using a simple gnotobiotic model that allows full control over the diet, the host, and the members of its microbiota, and combine large-scale metabolomics, precise metabolite tracking, and genetic and biochemical approaches. Nuclear Magnetic resonance analyses were applied in combination with Mass spectrometry analyses to explore metabolic behavior of two model bacteria: Acetobacter pomorum and Lactoplantibacillus plantarum, naturally found in fly and larval gut. To explore metabolic interactions between the different actors, bacteria were cultivated alone and in co-cultivation, then in presence of the drosophila larvae. Exo and endo metabolome was explored and quantified by combination of NMR and MS for metabolic profiling and 13C isotopic profiling

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    HAL ENVT (Ecole Nationale Vétérinaire de Toulouse)
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