HAL ENVT (Ecole Nationale Vétérinaire de Toulouse)
Not a member yet
16577 research outputs found
Sort by
Improvements in RNA and DNA nanopore sequencing allow for rapid genetic characterization of avian influenza
No full textInternational audienceAvian influenza virus (AIV) currently causes a panzootic with extensive mortality in wild birds, poultry, and wild mammals, thus posing a major threat to global health and underscoring the need for efficient monitoring of its distribution and evolution. We here utilized a well-defined AIV strain to systematically investigate AIV genetic characterization through rapid, portable nanopore sequencing by comparing the latest DNA and RNA nanopore sequencing approaches and various computational pipelines for viral consensus sequence generation and phylogenetic analysis. We show that the latest direct RNA nanopore sequencing updates improve consensus sequence generation, but that the application of the latest DNA nanopore chemistry after reverse transcription and amplification outperforms, such native viral RNA sequencing by achieving higher sequencing accuracy and throughput. We additionally leveraged the direct RNA nanopore sequencing data for the detection of RNA modifications, such as N6-methyladenosine and pseudouridine, which play a role in viral immune evasion. Finally, we applied these sequencing approaches together with portable AIV diagnosis and quantification tools to environmental samples from a poultry farm, demonstrating the feasibility of nanopore sequencing for on-site non-invasive AIV monitoring in real-world outbreak scenarios
Intestinal involvement in graft versus host disease in children: An overview by the ESPGHAN Gastroenterology Committee
No full textInternational audienceGraft versus host disease (GVHD) is a complication that frequently occurs after haematopoietic stem cell transplantation and concerns many children in paediatric haematology‐oncology and bone marrow transplantation departments. It can affect various organs, with the skin, gastrointestinal tract and liver being the most commonly involved. To confirm intestinal GVHD and to rule out differential diagnoses endoscopy is frequently needed. Currently, there are no specific consensus recommendations concerning the best method for endoscopic exploration and medical management of this disease in children, with limited studies available, including a low number of patients. Sigmoidoscopy could be initially proposed under sedation. If sigmoidoscopy is normal or if a general anaesthesia is required, colonoscopy and upper endoscopy should be planned, avoiding duodenal biopsy because of the risk of duodenal haematoma. Regarding therapeutic options, corticosteroids are the first‐line treatment for GVHD. Ruxolitinib, a Janus kinase inhibitor, is indicated for children aged 12 years and older with acute or chronic GVHD who have an inadequate response to corticosteroids or other systemic therapies. Nutritional support has a key role in the management of intestinal GVHD and should be considered to guarantee the best possible evolution of intestinal GVHD
Untargeted identification of pesticides metabolites to study their effects on metabolic and Parkinson diseases
No full textInternational audienceIntroduction The exposome concept has led to the toxicological assessment of pollutant mixtures. To understand consequences of chronic dietary exposure to pesticide cocktails on Parkinson and metabolic diseases, 2 preclinical studies were performed with mice exposed to the individual admissible daily intake (ADI) of different pesticides in mixture for 20 or 52 weeks. The impact of pesticides may depend on the biotransformation of each one that could be altered when pesticides are in combination. Thus, the characterization of residues (active substance and its metabolites) would not only support exposure but also provide a better insight of the observed effects. However, in a context of low-dose exposure and in the absence of commercial standards, detecting, identifying, and quantifying metabolites is challenging. Methods For the first study of the metabolic effects of pesticide exposure, urinary samples of mice exposed or not to the ADI of pesticides and fed a chow or a western diet were collected upon 20 weeks of exposure. For the second study, urinary samples of a mouse model expressing human alphasynuclein that recapitulates neuronal lesions in subjects with neurodegenererative diseases, and exposed or not to the ADI of a cocktail of pesticides, were collected at different time points of the 52 weeks period of exposure. Samples were analyzed using reversed-phase LC with HRMS detection (TIMS-ToF, Bruker) with a suspect screening approach with a list of suspected compounds, including the studied pesticides, their known metabolites, and putative ones, was screened and identified.Preliminary data For both studies, metabolites of pesticides were identified using MS/MS experiments acquired with the PASEF mode, and using CCS measurements acquired by ion mobility analyses. Comparisons with rare standards enabled level 1 identifications, but in most cases, annotations were achieved with the interpretation of fragment ions and CCS, assisted by in silico tools. By this way, we were able to detect pesticide metabolites following low-dose exposure. Interestingly, different signal intensities of each metabolite between each studied dose or time point and, more importantly, between the different diets or mouse models, were observed. Following the complex identification of pesticides biotransformed products without standard, their HRMS detection and quantification at low doses highlighted a link between the type of diet and the bioavailability of pesticides. Similarly, concentrations of pesticides metabolites were found to be different in the mouse model expressing human alphasynuclein that recapitulates neuronal lesions. Finally, these two studies illustrate that recent advances in mass spectrometry, in particularly ion mobility, allow the detection, identification, and quantification of low-concentration biomarkers of exposure, facilitating a better understanding of the effects of xenobiotics within the context of exposome
Implants régénératifs en silicone dans un modèle de lésion cérébrale aiguë chez le marmouset : caractérisation de la reconstruction tissulaire
No full textStroke is the main cause of acquired physical disability in adults. Ischemic stroke is the most common, often caused by a cerebral artery occlusion due to a blood clot. Various therapeutic strategies have already been explored, none showing convincing results in the subacute and chronic phases. Inserting biomaterial implants into damaged brain areas could represent a possible therapeutic approach to be further explored. In this study, the effect on tissue reconstruction (neuro-, glio- and angiogenesis) of silicone biomaterials implantation in a stroke model with malonate injection into the primary motor cortex of marmosets (Callithrix jacchus) was investigated. Implants seem to increase regeneration within the lesion. Reconstructed tissue characteristics on neuronal, glial, vascular and microglial markers are not altered by implants. Silicone implants appear to be an encouraging therapeutic strategy in regenerative medicine.L’accident vasculaire cérébral (AVC) représente la première cause de handicap physique acquis de l’adulte. L’AVC ischémique est le plus fréquent et souvent causé par l’occlusion d’une artère cérébrale par un caillot sanguin. Différents axes thérapeutiques ont déjà été explorés sans résultat probant en phase subaiguë à chronique. La greffe d’implants dans les zones cérébrales lésées représente un des axes thérapeutiques possible.Dans cette étude, l’effet de l’implantation de biomatériaux en silicone sur la reconstruction tissulaire (neuro-, glio- et angiogenèse) est étudié dans un modèle d’AVC par injection de malonate dans le cortex moteur primaire chez le marmouset (Callithrix jacchus). Les implants semblent augmenter la régénération dans la lésion et n’altèrent pas les caractéristiques du tissu en reconstruction sur les marqueurs neuronaux, gliaux, vasculaires et microgliaux. Les implants en silicone semblent être une stratégie thérapeutique encourageante en médecine régénérative
Multiomic analysis of different horse breeds reveals that gut microbial butyrate enhances racehorse athletic performance
No full textInternational audienceGut microbes play a vital role in host physiology, but whether specific bacterial functions contribute to the exceptional athletic performance of racehorses needs to be better understood. Here, we identify an association of gut butyrate-producing bacteria with athletic performance in racehorses (Thoroughbred horse). Butyrate-producing bacteria and microbial butyrate synthesis genes were significantly enriched in the racehorse gut, and the GC-MS results confirmed this conclusion. Using a mouse model, we demonstrated that sodium butyrate is sufficient to increase treadmill run time performance. We also show that butyrate improves the host response to exercise, significantly altering muscle fibre type in skeletal muscle, and increasing muscle mitochondrial function and activity. In addition, in-depth analysis of the published data showed that the gene for the synthesis of butyrate was also significantly enriched in the gut microbes of human athletes. Overall, our study indicates that gut microbial butyrate improves run time via the gut-muscle axis, providing novel insights into gut microbial functions and paving the way for improving athletic performance by targeted gut microbiome manipulation
Evaluation of nematode susceptibility and resistance to anthelmintic drugs with a WMicrotracker motility assay
No full textInternational audienceGrazing ruminants suffer from various helminth infections particularly those caused by gastrointestinal nematode (GIN) parasites, which have a considerable impact on their welfare and productivity. To treat these infections, the intensive use of macrocyclic lactone (ML) anthelmintics has led to the emergence of drug-resistant parasite populations worldwide. The standard method for detecting resistance, the Faecal Egg Count Reduction Test (FECRT), is susceptible to misinterpretation, leading to flawed management decisions that undermine parasite control efforts. Thus, there is a pressing need for robust resistance detection methods in field parasites. We investigated the potential of the WMicrotracker motility assay (WMA), previously unexplored in ML resistance assessment. The assay first compared ivermectin (IVM) susceptibility among wild-type Bristol N2 (N2B), IVM-selected (IVR10), and nhr-8 loss-of-function (AE501; nhr8(ok186)) Caenorhabditis elegans strains. Dose-response curves indicated that IVR10 had a 2.12-fold reduction in sensitivity to IVM compared to N2B. Additionally, cross-resistance assessment showed that IVR10 exhibited decreased sensitivity to moxidectin (MOX) and eprinomectin (EPR) relative to N2B. Further investigation conducted on Haemonchus contortus revealed significant differences in drug potency between susceptible and resistant isolates, with MOX demonstrating the highest efficacy. Resistance factors (RF) highlighted the substantial resistance of the isolate collected in a farm with EPR-treatment failure. The WMA effectively discriminated susceptible from resistant isolates in both C. elegans and H. contortus. Our findings demonstrate, for the first time, the relevance of WMA as a phenotypic assay for detecting ML resistance in nematodes by measuring their motility response. This research sheds light on a novel approach for monitoring drug resistance, vital for effective parasite management strategies
Atlas d’échographie abdominale chez la chèvre domestique
No full textThis study aims to present a detailed review of the healthy abdominal organs of goats as visualized through ultrasound, facilitating the performance of abdominal ultrasound examinations by veterinarians. As the popularity of goats as pets con.nues to rise, the demand for individualized care has significantly increased in recent years. Consequently, the application of cutting-edge ultrasound technology enables the provision of precise descriptions for each organ, accompanied by a brief overview of the major issues encountered with these organsCette thèse a pour objectif de fournir une revue de l’aspect échographique des organes abdominaux sains de caprins pour faciliter la réalisation d’échographies abdominale par les vétérinaires praticiens. La chèvre devenant de plus en plus un animal de compagnie pour certains particuliers, la demande de prise en charge individuelle pour les caprins est en constante augmentation ces dernières années. Pour chaque organe, l’utlisateur trouvera une description de l’organe, des images échographiques de l’organe sain ainsi qu’un bref résumé des principales affections rencontrées par cet organe
Phoenics: a novel statistical approach for longitudinal metabolomic pathway analysis
No full textInternational audienceMetabolomics describes the metabolic profile of an organism at a given time by the concentrations of its constituent metabolites. When studied over time, metabolite concentrations can help understand the dynamical evolution of a biological process. However, metabolites are involved into sequences of chemical reactions, called metabolic pathways, related to a given biological function. Accounting for these pathways into statistical methods for metabolomic data is thus a relevant way to directly express results in terms of biological functions and to increase their interpretability. Methods We propose a new method, phoenics, to perform differential analysis for longitudinal metabolomic data at the pathway level. In short, phoenics proceeds in two steps: First, the matrix of metabolite quantifications is transformed by a dimension reduction approach accounting for pathway information. Then, a mixed linear model is fitted on the transformed data. Results This method was applied to semi-synthetic NMR data and two real NMR datasets assessing the effects of antibiotics and irritable bowel syndrome on feces. Results showed that phoenics properly controls the Type I error rate and has a better ability to detect differential metabolic pathways and to extract new impacted biological functions than alternative methods. The method is implemented in the package phoenics available on CRA
Ceftobiprole in Critically Ill Patients: Proposal for New Dosage Regimens
No full textInternational audienceBackground: Ceftobiprole is a broad-spectrum cephalosporin. It is currently approved for the treatment of community- and hospital-acquired pneumonia. However, the recommended dosage regimen of ceftobiprole may not be sufficient to achieve the optimal pharmacokinetic/pharmacodynamic criterion in critically ill patients. The study aimed to evaluate whether the dosage regimens proposed by the manufacturers ensure that the optimal pharmacokinetic/pharmacodynamic criterion is achieved in over 90% of critically ill patients. Methods: Ceftobiprole concentrations were measured in 27 patients admitted to intensive care unit. An external evaluation of published population pharmacokinetic models was performed using simulations. The model that best described the data was used to evaluate the dosage regimens proposed for intensive care unit patients by evaluating the probability of attaining the optimal pharmacokinetic/pharmacodynamic criterion (100% fT > 4 * minimum inhibitory concentration). In addition, the same model was used to suggest dosage regimen adjustments for these patients. Results: Of the 4 models evaluated, Muller's population pharmacokinetic model was selected as the best for describing the concentrations observed in 27 patients. Simulations performed with this model have shown that the manufacturer's dosing regimens do not achieve the optimal pharmacokinetic/pharmacodynamic criterion in critically ill patients. Consequently, adaptation of dosing regimens to ensure ceftobiprole effectiveness in at least 90% of the patients was proposed. Conclusions: The proposed dosing regimens can be used to guide ceftobiprole administration in critically ill patients. However, measurement of ceftobiprole plasma concentration remains essential, at least once, to confirm patient exposure
Pharmacokinetic–Pharmacodynamic Cutoff Values for Doxycycline in Pigs to Support the Establishment of Clinical Breakpoints for Antimicrobial Susceptibility Testing
No full textInternational audienceThis meta‐analysis provides a population model of doxycycline (DOXY) disposition in pigs for computation of PK/PD cutoff values corresponding to differing modalities of DOXY administration orally in pigs. This analysis enables establishment of specific clinical breakpoints for the development of antimicrobial susceptibility testing of DOXY in pigs. The meta‐analysis of 380 data sets, totaling 3295 plasma concentrations obtained from 300 pigs weighing 8.5–101 kg, was performed using a non‐linear mixed effect model. The plasma clearance for a typical 50 kg BW pig was estimated to be 0.259 L/kg/h with a corresponding plasma half‐life of 7.33 h. The bioavailability of DOXY administered in feed under field conditions was estimated to be 50%, with a large between‐subject variability of 84.8%. The bioavailability of DOXY in solution in drinking water was significantly lower (30.7%) but much less variable, with a between‐subject variability of 34.3%. Several dosing schedules (5 to 20 mg/kg per day) for two administration modalities (drinking water vs. food) were simulated to calculate the corresponding PK/PD cutoffs. The highest PK/PD cutoff of 0.50 mg/L was obtained for DOXY administered in feed at 20 mg/kg BW