École Nationale Vétérinaire d'Alfort

Background Carboplatin is a human chemotherapeutic agent which is frequently used in dogs for the management of solid tumors. In human patient, its dosage is adjusted carefully, based on the creatinine clearance computation. In dogs however, the pharmacokinetics of carboplatin is poorly known and the dose 300 mg/m2 is based mostly on empirical data. Here, we aimed at characterizing the pharmacokinetics of carboplatin and determined the influence of several covariates, including creatinine plasma concentration and neutering status, in dogs, and used this model to predict myelotoxicity. Results Sixteen client owned dogs were included after carboplatin administration (300 mg/m²). For each animals, three to four plasma samples were collected and free plasma concentration of carboplatin was determined by HPLC/MS and analysed using Monolix® software with Non-linear mixed effect modelling. A mono-compartmental model best described the plasma concentration of carboplatin with log plasma creatinine concentration and sterilization status as covariates. After adjustment with the covariates, median population clearance was 3.62 [3.15 – 4.12] L/h/kg and volume of distribution was 3.93 [3.84 – 4.14] L/kg. The application of this model in 14 additional dogs demonstrates that individual drug exposure (model-predicted Area Under the Curve) predicted thrombocyte blood reduction (Pearson coefficient r² = 0.73, p = 0.002) better than dose after 14 days following administration of carboplatin. Conclusion Based on our results, plasma creatinine concentration and the sterilization status are relevant explanatory covariates for the pharmacokinetics variability of carboplatin in client owned dogs. Dose adjustment based on these parameters could represent a promising strategy for minimizing thrombocyte toxicity.

Background Assessing farm animals’ welfare is crucial, yet practical physiological tools are still lacking. In this study, we tested whether the peripheral blood mononuclear cell (PBMC) transcriptome shows variations in association with sows’ welfare. To do this, we compared animals whose welfare states were assumed to differ due to their lives in more or less enriched environments and to their different dominance statuses. Sows were housed in a conventional (C, n = 36) or enriched (E, n = 35) environments from gestation day 0 (G0) until three weeks before farrowing (G105), after which they were transferred to individual farrowing crates. From G99 to G103, behavioral analyses were conducted, and sows’ dominance status was evaluated. A subset of 28 multiparous sows (C, n = 14 and E, n = 14) was selected for the collection of saliva on G35 and G98 and hair on G98 for cortisol measurement, and of blood samples for PBMC transcriptome analysis on G98 and on lactation day 12 (L12). Results Both environmental enrichment (EE) and dominance status influenced cortisol and variables related to social and exploratory behavior, indicating an influence on sows’ welfare. In the transcriptomic analysis, among the 12,260 genes submitted to differential analysis on G98, EE impacted 31 genes, while dominance status impacted 449 genes. Compared with subordinate sows (SUB), dominant (DOM) sows exhibited an upregulation of genes related to inflammatory process and plasma cell function, and downregulation of genes related to B-cell activation. In groups of sows, dominance status is partly related to sows’ parity; therefore, we compared the effect of dominance with that of parity. Some common genes emerged when comparing high-parity (HP) vs. low-parity (LP) sows (542 differentially expressed genes (DEGs), including 180 in common with dominance-related genes), indicating that some effects of dominance on the transcriptome during gestation were in fact more due to age or reproductive cycles than to dominance itself. EE and dominance effects appeared relatively short-term, as DEG numbers decreased on L12 (four DEGs for E vs. C, 25 for DOM vs. SUB). Conclusions Dominance status exerted a more pronounced influence on sows’ PBMC transcriptome than did environmental enrichment. In particular, dominance status modulated genes associated with B cells and plasma cell functions. Some of the genes identified in this study could be tested in the future as potential molecular markers of well-being.

Background Hypoadrenocorticism in cats is uncommonly reported. Most reports consist of cats with hyponatremia, hyperkalemia, or both. Hypothesis/Objectives To describe clinical findings, treatment response, and outcome in cats diagnosed with hypoadrenocorticism, including cats with abnormal and normal serum sodium and potassium concentrations. Animals Forty‐one cats with hypoadrenocorticism; 36 with and 5 without abnormal serum sodium and potassium concentrations. Methods Multicenter retrospective observational study. Data for the entire cohort were assessed using descriptive statistics and differences between cats with and without abnormal serum sodium and potassium concentrations were evaluated. Results Median age was 5.7 years (range, 0.2‐13.8). Twenty‐three (56%) cats were male and 18 (44%) were female. Cats with hyponatremia, hyperkalemia, or both were less likely to have a history of vomiting (P = .01) but more likely to be hypothermic (P = .03), dehydrated (P = .04) or weak (P = .04) on examination, compared with nonhyponatremic and nonhyperkalemic cats. Frequency of hypercalcemia was 31.7%. Exocrine pancreatic insufficiency (EPI) was diagnosed in 4/7 cats tested; all 4 had concurrent cobalamin deficiency. Thirty‐five (85.4%) cats survived to discharge. In 2 cats, hypoadrenocorticism occurred secondary to lymphoma. Median survival time (MST) for all‐cause mortality was 2035 days (95% confidence interval [CI], 294‐4380 days); MST for disease‐specific mortality was not reached. Conclusions and Clinical Importance Approximately one‐third of cats with hypoadrenocorticism had hypercalcemia. In some cases, hyponatremia and hyperkalemia were not observed. Cats with nonneoplastic associated hypoadrenocorticism that survive initial hospitalization can have a favorable long‐term prognosis. Testing for EPI may be warranted in cats with hypoadrenocorticism.

Congenital absence of the vas deferens (CAVD) is a syndrome with a heterogeneous presentation: bilateral (CBAVD) or unilateral (CUAVD), complete or partial and associated or not with other anomalies of the male urogenital system. A turning point came in 1968 when CBAVD was associated with cystic fibrosis and its CFTR gene mutations. Genetic studies then revealed that a minority of CBAVD but a majority of CUAVD are CFTR ‐independent. In the literature, reference is classically made to two sources from the 18th and 19th century: Hunter and Reverdin. This scarcity prompted us to look for additional observations of CAVD. By a meticulous bibliographical search, we identified a corpus of 10 European observations (8 CUAVD and 2 CBAVD) some of them richly illustrated. They were collected between 1755 and 1876 throughout adult men autopsies. We also provided their primary and unambiguous sources. Analysis of the reported data revealed some interesting facts: both CBAVD cases were unlikely linked to cystic fibrosis and half of CUAVD cases were associated with an ipsilateral kidney absence, suggesting a CFTR ‐independent pathophysiology. Moreover, the anatomical details of the anomalies raise interesting embryological questions we have tried to address in the light of current data. This work made it possible to identify new historical sources dealing with male genital tract pathologies. It sheds light on the origins of andrology and opens up interesting prospects for research and education in the field.

Background The aim of this study was to assess the safety and efficacy of human umbilical cord mesenchymal stromal cells (hUC-MSCs) patch used as an adjuvant therapy in fetal myelomeningocele (MMC) surgery in the ovine model. Methods hUC-MSCs were isolated from human umbilical cords (UC) using the explant method, cultured and characterized. hUC-MSCs were then embedded in a fibrin patch. MMC were surgically created at 75 days of gestation and repaired at 89 days of gestation in sheep fetuses. Two groups were compared: the hUC-MSCs group in which MMC was repaired using a cellular patch and the control group, in which MMC was repaired using an acellular patch. Safety was evaluated by clinical ewes’ monitoring during gestation, and clinical and histological examinations of lambs after birth. Efficacy was assessed by clinical neurological evaluation at 2 and 24 h of life using the sheep locomotor rating scale and by histological analyses. Results Among the 17 operated lambs, nine were born alive: six in the hUC-MSCs group and three in the control group. Overall fetal loss was 47% (8/17) without differences between the two groups. No fever was reported in ewes. No tumors were detected in clinical and histological examinations in the lambs. At 24 h of life, mean Sheep Locomotor Rating score was higher in the hUC-MSCs group than in the control group: 15.0 versus 2.0 (p = 0.07). Histological analyses showed a higher large neurons density in the hUC-MSCs group in comparison with the control group: 9.9 versus 6.3/mm² of gray matter (p = 0.04). Lambs in the hUC-MSCs group had lower fibrosis around the spinal cord and at the level of the MMC scar: 70.9 versus 253.7 μm (p = 0.10) and 691.3 versus 1684.4 μm (p = 0,18), respectively. Conclusions Ovine fetal repair of MMC using human UC-MSCs seems to be an effective and safe procedure.

In France, in recent years, the field of veterinary medicine has witnessed a growing interest in veterinary telemedicine, driven by rapid technological advancements and a decline in the availability of veterinarians, particularly in remote and rural areas. However, there is a scarcity of literature addressing the barriers and facilitators of implementing telemedicine in veterinary practice. Therefore, this study aims to investigate the factors that influence the adoption of veterinary telemedicine for bovine, poultry and swine in France. Insights from both farmers and veterinarians were collected and subjected to qualitative analysis utilizing the COM-B model of behavior change. Significant barriers and facilitators were identified. Major hurdles encompass technological limitations, regulatory complexities, and concerns regarding the evolution of the veterinary profession. Conversely, the expertise of veterinarians, coupled with their understanding of their clients’ farms, and the potential for remote interventions, emerged as primary facilitators. The study emphasizes the critical role of regulation in ensuring ethical standards and maximizing the benefits of telemedicine. With clear regulatory frameworks in place, telemedicine holds promise for enhancing animal health and optimizing veterinary practice.

Tick-borne encephalitis (TBE) is a vaccine-preventable viral infection that poses significant public health challenges, particularly in regions where tick-borne diseases are endemic. This case report describes a 2-year-old boy with confirmed abortive TBEV infection following a tick bite during travel to Switzerland. The patient developed fever and mild symptoms but did not exhibit central nervous system involvement. The case underscores the importance of raising awareness among healthcare providers and travelers from non-endemic areas, such as Serbia, about TBE risk and the potential benefits of preventive vaccination. Strategic immunization campaigns could mitigate the public health impact of travel-related TBE.

Background Variations in the distribution and prevalence of pathogens in ticks can have significant consequences for human health. Information on these variables in Transcaucasia is scarce, so the aim of our study was to conduct a large-scale study to detect selected tick-borne infectious agents in Armenia. Methods Overall, 209 adult ticks were collected from different hosts including 4 samples from human clothes. We tested ticks using high-throughput microfluidic single-cell real-time PCR to detect 42 genospecies of pathogens. We used GIS to determine biotic and abiotic factors governing the prevalence of pathogens and applied statistical analyses to test the association between prevalence of pathogens depending on hosts, locality and environment. Results From 209 samples, 134 were positive to targeted pathogens. Anaplasma phagocytophilum Foggie, 1949 was the most prevalent case (44%). The highest overall prevalence was observed in ticks from sheep (74%), followed by cows (67%) and calves (60%). The highest multiple infection rates were also detected in sheep (40%) and calves (40%) followed by cows (28%). One statistically significant association was found among co-infections (P<0.05). The prevalence of pathogens varied according to locality. The abundance of Anaplasma spp. is significantly correlated with “slope” and “vegetation” factors. Similar patterns were detected for other pathogens. Conclusion This was the first large-scale survey of multiple tick-borne pathogens in Armenia and Transcaucasia. The results of this study shed light on spatial variations in pathogen infection rate among adult ticks found on hosts and underline a number of environmental determinants of pathogen distribution among ticks.

Background Mosquitoes serve as vectors for numerous pathogens, posing significant health risks to humans and animals. Understanding the complex interactions within mosquito microbiota is crucial for deciphering vector-pathogen dynamics and developing effective disease management strategies. Here, we investigated the nested patterns of Wolbachia endosymbionts and Escherichia-Shigella within the microbiota of laboratory-reared Culex pipiens f. molestus and Culex quinquefasciatus mosquitoes. We hypothesized that Wolbachia would exhibit a structured pattern reflective of its co-evolved relationship with both mosquito species, while Escherichia-Shigella would display a more dynamic pattern influenced by environmental factors. Results Our analysis revealed different microbial compositions between the two mosquito species, although some microorganisms were common to both. Network analysis revealed distinct community structures and interaction patterns for these bacteria in the microbiota of each mosquito species. Escherichia-Shigella appeared prominently within major network modules in both mosquito species, particularly in module P4 of Cx. pipiens f. molestus, interacting with 93 nodes, and in module Q3 of Cx. quinquefasciatus, interacting with 161 nodes, sharing 55 nodes across both species. On the other hand, Wolbachia appeared in disparate modules: module P3 in Cx. pipiens f. molestus and a distinct module with a single additional taxon in Cx. quinquefasciatus, showing species-specific interactions and no shared taxa. Through computer simulations, we evaluated how the removal of Wolbachia or Escherichia-Shigella affects network robustness. In Cx. pipiens f. molestus, removal of Wolbachia led to a decrease in network connectivity, while Escherichia-Shigella removal had a minimal impact. Conversely, in Cx. quinquefasciatus, removal of Escherichia-Shigella resulted in decreased network stability, whereas Wolbachia removal had minimal effect. Conclusions Contrary to our hypothesis, the findings indicate that Wolbachia displays a more dynamic pattern of associations within the microbiota of Culex pipiens f. molestus and Culex quinquefasciatus mosquitoes, than Escherichia-Shigella. The differential effects on network robustness upon Wolbachia or Escherichia-Shigella removal suggest that these bacteria play distinct roles in maintaining community stability within the microbiota of the two mosquito species.

Culicoides are vectors that can transmit many different pathogens to mammals — including humans, and domestic and wild animals — and birds. In order to take preventive measures against any vector-borne disease, it is important to gather information on both the host and vector species. Culicoides species are mainly mammalophilic, ornithophilic or ornithophilic/mammalophilic, but females have also been found to occasionally feed on engorged insects. A recent systematic review based on three groups of key words investigated Culicoides on farms, and asserted that 92 species (including four not present species) have been reported among cattle in mainland France and Corsica. We have re-evaluated the presence of Culicoides species in cattle in France using the same data of the review. Our data show that only 18 species are reported among cattle. Furthermore, our research used molecular and indirect investigations to analyse Culicoides species that had been feeding on cattle. Our results demonstrate that 45 species feed on cattle out of 92 species present in France. The paper discusses the relevance of data in the literature when investigating hosts of Culicoides species.

Background: Intravenous regional limb perfusion (IVRLP) of antibiotics is a therapeutic method used to treat distal limb infections in horses. This study objectives were to determine pharmacokinetic parameters and tolerance of sodium benzylpenicillin (NaBP) administered via IVRLP; to compare the feasibility, tolerance and efficacy of performing IVRLP on a flexed limb versus a weightbearing limb and finally to predict efficacy of IVRLP with gentamicin or NaBP. A prospective crossover study was performed with six horses included in the study. Each horse underwent four phases of antibiotic infusion (gentamicin 2.2mg/kg vs. NaBP 4.12mg/kg of BP) and limb position (weightbearing vs. flexed). Each antibiotic administration was followed by several synovial and blood samples to assess antibiotic concentrations. Inflammation and secondary sensibility were assessed at the injection site and at the sampled joint. A PK/PD analysis was conducted to predict the efficacy of IVRLP by estimating values of the AUC/MIC index for different minimum inhibitory concentrations (MIC). Results: High synovial concentrations of NaBP and gentamicin were obtained, with high variability between horses. NaBP IVRLP was well tolerated but cephalic vein inflammation score was significantly higher following NaBP infusion compared with gentamicin. For all horses and both antibiotics, synovial antibiotics exposures were significantly higher in weightbearing limbs than in flexed limbs. We found significantly higher cephalic vein inflammation scores in flexed limbs compared to weightbearing limbs. Regarding efficacy, daily dose of 2.2mg/kg of gentamicin was adequate to treat synovial infections involving E. coli or S. aureus , even when considering resistant strains. For NaBP, a daily or every-other-day dose of 4.12mg/kg of BP was adequate to treat S. equi and sensitive S. aureus synovial infections. Conclusions: These data suggest that daily IVRLP of NaBP (4.12mg/kg of BP) could be an effective method for treatment of infections of the distal limb for susceptible bacteria with MIC ≤ 2µg/mL, with discrete local inflammation at the injection site; whereas IVRLP with 2.2mg/kg of gentamicin could be effective to treat infections with susceptible bacteria with MIC ≤ 16µg/mL. Performing IVRLP on a weightbearing limb led to increased antibiotics exposure of the fetlock joint and to a better tolerance than the flexed limb method.

During focal ischemia, neurons can use lactate as an alternative source of energy through its oxidation into pyruvate by the lactate dehydrogenase (LDH). After cardiac arrest, the neurological consequences of this phenomenon are unknown. Experimental study. Experimental laboratory. Male New-Zealand rabbits. Animals were surgically instrumented and randomly divided into five groups receiving short infusion duration of either lactate or pyruvate or a pre-cardiac arrest infusion of oxamate (an inhibitor of the lactate dehydrogenase) or injection of fluorocitrate (an inhibitor of astrocytic tricarboxylic acid), or Saline (lactate, pyruvate, Oxa, FC and Control groups, respectively). After randomization, animals were submitted to 10 min of ventricular fibrillation and subsequent resuscitation. All animals were then either followed during 4 h, for the evaluation of the cerebral net uptake and concentrations of metabolites by microdialysis (n = 6 in each experimental group, n = 12 in control group), or during 48 h for the evaluation of their neurological outcome (n = 7 in each groups and n = 14 in control group). Cardiac arrest was associated with a dramatic increase in cerebral net uptake of lactate during 120 min after resuscitation, which was increased by lactate or pyruvate administration. This was associated with an increase in the mean neurological dysfunction score (66.7 ± 4.7, 79.0 ± 4.5 vs 57.7 ± 1.5 in Lactate, Pyruvate and Control group respectively) at 48 h after cardiac arrest. Oxamate and FC administration were associated with a lower lactate cerebral uptake after cardiac arrest and with an improvement of the neurological recovery (28.85 ± 9.4, 23.86 ± 6.2 vs 57.7 ± 1.5 in Oxa, FC and Control group respectively). After cardiac arrest, immediate isotonic lactate or pyruvate administration is deleterious. Pre-cardiac arrest LDH inhibition was potently neuroprotective in this setting.

How living systems achieve precision in form and function despite their intrinsic stochasticity is a fundamental yet ongoing question in biology. We generated morphomaps of preimplantation embryogenesis in mouse, rabbit, and monkey embryos, and these morphomaps revealed that although blastomere divisions desynchronized passively, 8-cell embryos converged toward robust three-dimensional shapes. Using topological analysis and genetic perturbations, we found that embryos progressively changed their cellular connectivity to a preferred topology, which could be predicted by a physical model in which actomyosin contractility and noise facilitate topological transitions, lowering surface energy. This mechanism favored regular embryo packing and promoted a higher number of inner cells in the 16-cell embryo. Synchronized division reduced embryo packing and generated substantially more misallocated cells and fewer inner-cell–mass cells. These findings suggest that stochasticity in division timing contributes to robust patterning.

This literature-based review aims to distinguish studies describing co-infection with tick-borne pathogens from those describing co-detection or co-exposure scenarios. The review analyzed 426 papers and identified only 20 with direct evidence of co-infection in humans and animals, highlighting the need for accurate terminology and proposing definitions for co-infection, co-exposure and co-detection. Current diagnostic methods - including serology and molecular techniques - have limitations in accurately identifying real co-infections, often leading to misinterpretation. The review highlights the importance of developing laboratory models to better understand tick-borne pathogen interactions, and advocates improved diagnostic strategies for tick screening by testing their RNA for co-infections. Moreover, the establishment of additional animal models for pathogen co-infection will help develop our understanding of selection pressures for various traits of tick-borne pathogens (such as virulence and transmissibility) over time. This comprehensive analysis provides insights into the complexity of tick-borne pathogen co-infections and calls for precise diagnostic terms to improve the clarity and effectiveness of future research.

Background Dairy cattle breeds are populations of limited effective size, subject to recurrent outbreaks of recessive defects that are commonly studied using positional cloning. However, this strategy, based on the observation of animals with characteristic features, may overlook a number of conditions, such as immune or metabolic genetic disorders, which may be confused with pathologies of environmental etiology. Results We present a data mining framework specifically designed to detect recessive defects in livestock that have been previously missed due to a lack of specific signs, incomplete penetrance, or incomplete linkage disequilibrium. This approach leverages the massive data generated by genomic selection. Its basic principle is to compare the observed and expected numbers of homozygotes for sliding haplotypes in animals with different life histories. Within three cattle breeds, we report 33 new loci responsible for increased risk of juvenile mortality and present a series of validations based on large-scale genotyping, clinical examination, and functional studies for candidate variants affecting the NOA1, RFC5, and ITGB7 genes. In particular, we describe disorders associated with NOA1 and RFC5 mutations for the first time in vertebrates. Conclusions The discovery of these many new defects will help to characterize the genetic basis of inbreeding depression, while their management will improve animal welfare and reduce losses to the industry.

Body composition is an important parameter in diving animals intermittently fasting on land, such as southern elephant seals, as it is known to impact their time of departure at sea, swimming effort, foraging success, and survival. Deuterium labeled water is commonly used to assess total body water, but a precise indication of equilibration time in this species and reliable sample storage are lacking. We injected newly weaned southern elephant seal female pups with deuterium-labeled water. We thereafter blood sampled the seals several times to assess the equilibration time and body composition. We implemented two storage methods, flame-sealed capillaries and frozen serums stored at − 20 °C in a gas freezer. The frozen serums method was reliable as capillaries and safer to bring undamaged samples from the field. This method of determining body composition in wild animals is reliable and easily applicable for isolated and difficult-to-access fieldwork.

Body size has an impact on all biological functions and analyzing how body size impacts functional traits such as locomotion is critical. Body size does not only vary across species but also during ontogeny. Indeed, juvenile animals are often at a competitive disadvantage due to their smaller absolute size. Consequently, understanding size‐ and age‐related changes in the locomotor system is critical for our understanding of adult phenotypes. Here, we address this question by exploring growth of the hind limb muscles in two species of closely related baboons that differ in their ecology, the olive baboon, Papio Anubis , the Guinea baboon, and Papio papio . To do so, we dissected 40 P. anubis and 10 P. papio and measured the mass and physiological cross‐sectional area (PCSA) of the hind limb muscles. Our results showed no sexual differences in size‐ or age‐related growth patterns, but did show differences between species. Whereas the scaling of muscle mass and PCSA was largely isometric in P. anubis , allometric scaling was more common in P. papio . Despite these differences between species, the knee extensors and external rotators at the knee scaled with positive allometry in both species highlighting their important role during adult locomotion. Although life‐history data for P. papio are scarce, we suggest that differences between species may be associated with differences in adult body size and age of locomotor independence between species.

An infection with the tick-borne Rickettsia helvetica has been associated with a broad spectrum of clinical manifestations in humans, but patients are only seldomly reported. Understanding its disease etiology necessitates well-stablished infection models, improving to recognize and diagnose patients with R. helvetica infection and facilitating the development of effective control strategies. In this study, we used C3H/HeN mice as a model to establish R. helvetica infection, achieving a high infection prevalence (89-100%). While the liver and the spleen DNA consistently tested positive for infection in all challenged mice, additional infected organs included the kidneys, heart, and the lungs. Notably, a low prevalence of infection was observed in I. ricinus nymphs fed on R. helvetica-challenged mice. In addition, larvae were refractory to infection, suggesting that ticks exhibit low susceptibility to the pathogen. To the best of our knowledge, this is the first study of an animal model for R. helvetica infection. It serves as a valuable tool for advancing research on the interactions among the bacterium and its vertebrate host.