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The purpose of this study was to describe a new hereditary sensory neuropathy in French spaniels resulting in analgesia and progressive mutilation of the distal extremities. Thirteen French spaniels (six females, seven males) from five different litters with acral mutilation were identified. Clinical signs were first noted between 3.5 and 12 months of age and typically consisted of sudden excessive and intense licking and biting of toes and/or footpads of one or several feet. This generally progressed rapidly into swollen digits, paronychia, footpad ulceration, and occasionally fracture and osteomyelitis. If the affected dogs were unrestrained, auto-amputation of claws, toes and footpads usually resulted. However, even in the more severe cases, affected dogs walked and ran on their mutilated feet without any evidence of lameness, pain or ataxia, and they allowed wound care without evidence of pain or discomfort. Dogs were otherwise healthy, with the exception of frequent secondary bacterial infections of the wounded feet. This disorder was clinically very difficult to manage, and the majority of the dogs were euthanized within days to months of diagnosis. None of the sires or dams of the affected dogs reported here were clinically affected. There was no apparent sex predilection. An autosomal recessive mode of inheritance was strongly suspected. The clinicopathological findings, the early age of onset and the disease progression in affected French spaniels were very similar to those reported for hereditary sensory neuropathy in German short-haired pointers, English pointers and English springer spaniels. Funding: Self-funded. [ABSTRACT FROM AUTHOR]

Competing Interests: Conflicts of interest: None declared for Julie Lefrançois. In the last 5 years, Frédéric Sauvé has received honoraria, consulting fees, and/or collaborated with CEVA, Royal Canin, Purina, Zoetis, Elanco, and Vétoquinol.

The hypothalamic arcuate nucleus (ARH) contains neurons vital for maintaining energy homeostasis that sense and respond to changes in blood-borne metabolic hormones. Despite its juxtaposition to the median eminence (ME), a circumventricular organ lacking a blood-brain barrier and thus exposed to circulating molecules, only a few ventral ARH neurons perceive these extravasating metabolic signals due to a poorly understood ME/ARH diffusion barrier. Here, we show in male mice that aggrecan, a perineural-net proteoglycan deposited by orexigenic ARH neurons, creates a peculiar ventrodorsal diffusion gradient. Fasting enhances aggrecan deposition more dorsally, reinforcing the diffusion barrier, particularly around neurons adjacent to fenestrated capillary loops that enter the ARH. The disruption of aggrecan deposits results in unregulated diffusion of blood-borne molecules into the ARH and impairs food intake. Our findings reveal the molecular nature and plasticity of the ME/ARH diffusion barrier, and indicate its physiological role in hypothalamic metabolic hormone sensing., (© 2024. The Author(s).)

Background: Allergen testing is used to select antigens included in the desensitisation vaccine. Intradermal skin test (IDT) is the gold standard in cats, yet allergen-specific immunoglobulin (Ig)E serological testing (ASIS) is often used. Feline data are lacking regarding the agreement between IDT and ASIS results., Hypothesis/objectives: The first objective of the study was to establish a colony of cats with naturally acquired feline atopic syndrome (FAS). Further objectives were to define their hypersensitivity disorder to detail the allergen tests results, and to assess similarity between the allergen tests., Animals: Thirty-five cats with FAS and 10 control cats., Materials and Methods: Enrolled cats went through a five phase-screening and quarantine process before joining the colony. An elimination diet trial was performed on all FAS cats. ASIS and IDT were consecutively performed on all cats under sedation., Results: Reactions to 34 allergens were compiled for the 45 cats. Global sensitivity and specificity of ASIS were 34.7% and 78.9%, respectively. Only flea (ICC = 0.26, p = 0.040) and Dermatophagoides pteronyssinus (ICC = 0.48, p < 0.001) allergens had a significant intraclass correlation (weak agreement). Two FAS cats had negative tests including one cat with a concomitant food allergy., Conclusions and Clinical Relevance: This study depicts the first reported colony of cats with naturally acquired FAS. This is the first feline study to compare and show the poor agreement between allergen tests with a panel of 34 allergens. This colony also harbours two cats with FAS with negative allergen tests. These may represent the first described cats with an intrinsic form of atopic syndrome., (© 2024 ESVD and ACVD.)

The pathogenesis of anal sacculitis has not been extensively investigated, although atopic dogs seem to be predisposed to the disease. The aim of this study was therefore to characterize and compare the bacterial microbiota and pro-inflammatory cytokines in the anal sacs of dogs from three groups (healthy dogs, untreated atopic dogs and atopic dogs receiving antipruritic treatment or allergen-specific immunotherapy) in order to determine whether changes could be at the origin of anal sacculitis in atopic dogs. Bacterial populations of anal sac secretions from fifteen healthy dogs, fourteen untreated and six treated atopic dogs were characterized by sequencing the V4 region of the 16S rRNA gene using Illumina technology. Proinflammatory cytokines were analyzed with the Luminex multiplex test. Community membership and structure were significantly different between the anal sacs of healthy and untreated atopic dogs (P = 0.002 and P = 0.003, respectively) and between those of untreated and treated atopic dogs (P = 0.012 and P = 0.017, respectively). However, the community structure was similar in healthy and treated atopic dogs (P = 0.332). Among the proinflammatory cytokines assessed, there was no significant difference between groups, except for interleukin 8 which was higher in the anal sacs of untreated atopic dogs compared to treated atopic dogs (P = 0.02), and tumor necrosis factor-alpha which was lower in the anal sacs of healthy dogs compared to treated atopic dogs (P = 0.04). These results reveal a dysbiosis in the anal sacs of atopic dogs, which may partially explain the predisposition of atopic dogs to develop bacterial anal sacculitis. Treatments received by atopic dogs (oclacitinib, desloratadine and allergen-specific immunotherapy) shift the microbiota of the anal sacs towards that of healthy dogs. Further studies are required to identify significant cytokines contributing to anal sacculitis in atopic dogs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 C. Bergeron et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The prevalence, anatomical distribution, or nature of cutaneous, hair and oral mucosal abnormalities (CHMAs) in cattle is uncertain., Objectives: To determine how often dairy cattle admitted to a veterinary teaching hospital (VTH) had CHMAs (except for foot and ear canal) on physical examination and if there was an age-related difference., Animals: Four hundred and thirty-three cattle: cattle <3 months (n = 85), cattle 3 to 24 months (n = 73), and cattle >24 months (n = 275)., Methods: In this descriptive, observational, prospective study, CHMAs of dairy cattle admitted to the VTH of the Université de Montréal were recorded over 1 year. Prevalences were calculated. Dermatological examinations were performed within 48 hours of admission, according to a glossary. Chi-square tests were used to compare prevalence between age groups., Results: The 433 cattle were mostly females (97.5%) and of the Holstein breed (89.8%). The prevalence of cattle <3 months presenting with at least 1 identifiable CHMA was 65% (55/85). In cattle 3 to 24 months old, it was 90% (66/73), and in cattle >24 months, it was 99.3% (273/275). There were significant differences (P < .001) between the prevalence of CHMAs localized on the ischia, ilia, stifles, hocks, carpi, flank, lateral neck, dorsal cervical, and cornual regions in cattle >24 months vs <3 months., Conclusions and Clinical Importance: CHMAs were highly prevalent and age-specific. Calluses on the carpi and hocks of cattle >24 months were the most common CHMAs., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Competing Interests: In the last 5 years, Eloi Guarnieri has no conflict of interest to declare. Frédéric Sauvé has received honoraria, consulting fees, and/or collaborated with Royal Canin, Purina, Zoetis, Elanco, and Vétoquinol.

Genomic characterization was conducted on 2 methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from 2 horses hospitalized during an overlapping period of time and 2 methicillin-sensitive S. aureus (MSSA) strains isolated from 2 distinct horses. Phylogenetic proximity was traced and the genotypic and phenotypic characteristics of the antimicrobial resistance of the strains were compared. Whole genome sequencing of MRSA strains for this report was similar but differed from whole genome sequencing of MSSA strains. The MRSA strains were closely related, belonging to sequence type (ST) 612, spa type t1257, and SCC mec type IVd2B. The MSSA strains were also closely related, belonging to ST1660, spa type t3043, and having no detectable staphylococcal cassette chromosome mec elements. All MSRA and MSSA strains were Panton-Valentine leukocidin negative. There were discrepancies in the genotypic analysis and the antimicrobial susceptibility testing (phenotypic analysis) of MRSA strains for rifampin, trimethoprim-sulfamethoxazole, gentamicin, amikacin, and enrofloxacin., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

The aim of the present study was to characterize the bacterial microbiota of anal sacs in healthy dogs using NGS. Swabs were used to sample the rectum and secretions from each anal sac in 15 healthy dogs. DNA was extracted from swabs and the V4 hypervariable region of the 16S rRNA gene was amplified and sequenced with Illumina MiSeq. Overall, 14 different bacterial phyla were identified in the rectum and in both anal sacs, the 5 main ones being Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, and Fusobacteria. The rectum had higher microbial diversity and richness than the left and right anal sacs. Community membership and structure significantly differed between the rectum and both anal sacs, but not between the right and the left anal sacs. This study showed that the diversity and richness of the bacterial microbiota of the anal sacs in dogs is greater than what has been reported in previous studies with culture-based methods. In conclusion, the bacterial microbiota of the anal sacs in dogs varies between individuals and differs from the rectal bacterial microbiota., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

The goals of this retrospective study were to: determine the frequency of methicillin-resistant Staphylococcus spp. (MRS) isolated from horses admitted to an equine veterinary teaching hospital in Quebec from 2008 to 2018, investigate the patterns of antimicrobial resistance (AMR), and evaluate the distribution of MRS and methicillin-sensitive Staphyloccocus spp. (MSS) by body site. During this period, 311 Staphylococcus spp. were isolated from 273 horses and 127 of these isolates were submitted to antimicrobial susceptibility testing. Of these 127 isolates, 24 (18.9%) were MRS, and among the S. aureus ( n = 76), 19 (25%) were MRS. The odds of detecting an MRS increased (25%) each year [95% confidence interval (CI) (1% to 55%), P = 0.039]. The highest frequencies of resistance were to tetracycline and gentamicin. Among the MRS isolates, 12% were susceptible to both tetracycline and gentamicin. The most frequently sampled body sites were "soft-tissues." There was no significant difference ( P = 0.93) in the body site distribution of MRS and MSS isolates., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

This case report describes the clinical and histopathological findings of an infection caused by equine herpesvirus-1 (EHV-1) in a horse showing respiratory signs and a papular, crusted and ulcerative dermatitis involving mucosae. This diagnosis was supported by real-time PCR positive for EHV-1 on nasal swabs and tissues., (© 2020 ESVD and ASVD.)

Competing Interests: Conflicts of interest: In the last 5 years, Frédéric Sauvé has received honoraria, consulting fees, and/or collaborated with Royal Canin, Zoetis, and Elanco.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by synaptic loss that leads to the development of cognitive deficits. Synapses are neuronal structures that play a crucial role in memory formation and are known to consume most of the energy used in the brain. Interestingly, AMP-activated protein kinase (AMPK), the main intracellular energy sensor, is hyper-activated in degenerating neurons in several neurodegenerative diseases, including AD. In this context, we asked whether AMPK hyper-activation could influence synapses' integrity and function. AMPK hyper-activation in differentiated primary neurons led to a time-dependent decrease in pre- and post-synaptic markers, which was accompanied by a reduction in synapses number and a loss of neuronal networks functionality. The loss of post-synaptic proteins was mediated by an AMPK-regulated autophagy-dependent pathway. Finally, this process was also observed in vivo, where AMPK hyper-activation primed synaptic loss. Overall, our data demonstrate that during energetic stress condition, AMPK might play a fundamental role in the maintenance of synaptic integrity, at least in part through the regulation of autophagy. Thus, AMPK might represent a potential link between energetic failure and synaptic integrity in neurodegenerative conditions such as AD.

Long-term memory formation depends on the expression of immediate early genes (IEGs). Their expression, which is induced by synaptic activation, is mainly regulated by the 3',5'-cyclic AMP (cAMP)-dependent protein kinase/cAMP response element binding protein (cAMP-dependent protein kinase (PKA)/ cAMP response element binding (CREB)) signaling pathway. Synaptic activation being highly energy demanding, neurons must maintain their energetic homeostasis in order to successfully induce long-term memory formation. In this context, we previously demonstrated that the expression of IEGs required the activation of AMP-activated protein kinase (AMPK) to sustain the energetic requirements linked to synaptic transmission. Here, we sought to determine the molecular mechanisms by which AMPK regulates the expression of IEGs. To this end, we assessed the involvement of AMPK in the regulation of pathways involved in the expression of IEGs upon synaptic activation in differentiated primary neurons. Our data demonstrated that AMPK regulated IEGs transcription via the PKA/CREB pathway, which relied on the activity of the soluble adenylyl cyclase. Our data highlight the interplay between AMPK and PKA/CREB signaling pathways that allows synaptic activation to be transduced into the expression of IEGs, thus exemplifying how learning and memory mechanisms are under metabolic control.

The efficacy of Oridermyl(®) (acaricidal/antibiotic/antifungal/anti-inflammatory ointment) and Revolution(®) (selamectin spot-on) was compared in a blinded randomized study on 24 adult cats with otoacariasis. Twelve cats were treated once daily for 10 d with Oridermyl(®) and 12 cats were treated on Day 0 with Revolution(®). Otitis was assessed with cytological counts of mean number of bacteria and yeast on Days 0 and 10, and scored clinically every other day. All auricular secretions were removed for mite count on Day 10. On Day 0, cytological examination confirmed the presence of secondary bacterial (24/24) and fungal (21/24) infections. No live mites were observed otoscopically after Day 4 and in auricular secretions at Day 10 in both groups. On Day 10, secondary infections were resolved for all cats treated with Oridermyl(®) but were present in all cats treated with Revolution(®). Improvement in clinical signs of otitis over time was superior in the Oridermyl(®) group (P < 0.001).

A 6-year-old Dachshund was presented with a 2-day history of lethargy, anorexia and cutaneous erythema, edema, and multifocal erythematous papules affecting the ventral abdomen, axillae, and groin. Microscopic examination revealed a sterile neutrophilic dermatitis resembling Sweet's syndrome; however, extracutaneous lesions were not present. The condition responded rapidly to corticosteroid therapy.

The purpose of this study was to evaluate the effect of the administration of meloxicam; carprofen; and a slow-acting disease modifying osteoarthritis agent, that contains chondroitin sulfate, purified glucosamine, and manganese ascorbate (CS-G-M), on thyroid function in dogs. Forty-six healthy (except for osteoarthritis) euthyroid dogs were blindly assigned to 3 treatment groups: meloxicam, carprofen, and CS-G-M. Each group received the recommended dose of the drug for 60 days. Sixteen other osteoarthritic euthyroid dogs, which received a placebo, were used as a control group to validate the study. For all groups, blood samples were collected on days 0, 30, and 60 to evaluate the serum total and free thyroxine, and endogenous thyrotropin concentrations. There were no significant differences among the treatment groups at each time or within each group over a 60-day period for all parameters. Moreover, none of these values were within the hypothyroid range. Based on the results of this study, the administration of meloxicam, carprofen, and CS-G-M did not affect canine thyroid function evaluation.

Several nonthyroidal illnesses in euthyroid dogs can affect the results of thyroid function testing, making interpretation of the results more difficult with an increased risk of overdiagnosing hypothyroidism. The purpose of this study was to evaluate the effect of chronic, moderate to severe, osteoarthritis on canine thyroid function. Ninety-six, healthy, client-owned dogs, 65 of which were suffering from moderate to severe osteoarthritis and 31 euthyroid dogs without any physical evidence of osteoarthritis, were used in this study. Blood samples were collected to evaluate serum basal total thyroxine (TT4), free thyroxine (FT4), and thyrotropin (TSHc) concentrations. Basal serum TT4 concentration was not affected by osteoarthritis in dogs. Mild, but statistically significant, differences were noticed in FT4 and TSHc concentrations among the 2 groups. However, this had limited clinical relevance, since virtually all values were within their reference range, and no dogs would have been misdiagnosed as hypothyroid. Therefore, based on the results of our study, osteoarthritis does not need to be considered a factor influencing thyroid function evaluation in dogs.

Coregulators for nuclear receptors (NR) are factors that either enhance or repress their transcriptional activity. Both coactivators and corepressors have been shown to use similar but functionally distinct NR interacting determinants containing the core motifs LxxLL and PhixxPhiPhi, respectively. These interactions occur through a hydrophobic cleft located on the surface of the ligand-binding domain (LBD) of the NR and are regulated by ligand-dependent activation function 2 (AF-2). In an effort to identify novel coregulators that function independently of AF-2, we used the LBD of the orphan receptor RVR (which lacks AF-2) as bait in a yeast two-hybrid screen. This strategy led to the cloning of a nuclear protein referred to as CIA (coactivator independent of AF-2 function) that possesses both repressor and activator functions. Strikingly, we observed that CIA not only interacts with RVR and Rev-ErbAalpha in a ligand-independent manner but can also form complexes with estrogen receptor alpha (ERalpha) and ERbeta in vitro and enhances ERalpha transcriptional activity in the presence of estradiol (E(2)). CIA-ERalpha interactions were found to be independent of AF-2 and enhanced by the antiestrogens EM-652 and ICI 182,780 but not by 4-hydroxytamoxifen and raloxifene. We further demonstrate that CIA-ERalpha interactions require the presence within CIA of a novel bifunctional NR recognition determinant containing overlapping LxxLL and PhixxPhiPhi motifs. The identification and functional characterization of CIA suggest that hormone binding can create a functional coactivator interaction interface in the absence of AF-2.

A method is described for the determination of 251 pesticide and degradation product residues in fruit and vegetable samples. Extraction of the sample with acetonitrile is followed by a salting-out step. Co-extractives are removed by passing a portion of the acetonitrile extract through an octadecyl (C18) solid-phase extraction cleanup cartridge and then, in a second cleanup, through a carbon cartridge coupled to an amino propyl cartridge. Determination is by gas chromatography with mass-selective detection in the selected-ion monitoring mode, and by liquid chromatography with post-column reaction and fluorescence detection for N-methyl carbamates. The method has been used for analysis of various fruits and vegetables, such as apple, banana, cabbage, carrot, cucumber, lettuce, orange, pear, pepper, and pineapple. Limits of detection range between 0.02 and 1.0 mg/kg for most compounds. Over 80% of the compounds have a limit of detection of < or = 0.04 mg/kg.

The purpose of this study was to evaluate the effects of the recombinant human thyroid-stimulating hormone (rhTSH) on serum total thyroxine (TT4) concentration in euthyroid dogs. Six healthy beagle dogs were used in each of the 3 phases of this study. Phase I: thyroid-stimulating hormone response tests were performed by using a total dose of 25 micrograms, 50 micrograms, and 100 micrograms of rhTSH, administered intravenously. Phases II and III: thyroid-stimulating hormone response tests were performed by using 50 micrograms of rhTSH administered by intramuscular and subcutaneous routes, respectively. In each phase and following all the administered doses of rhTSH, an increase in the serum TT4 concentration was noted, although it was not always significant. For phase I, there was a significant increase in serum TT4 concentrations. Based on this study, 50 micrograms was judged to be the optimal intravenous dose of rhTSH. For phases II and III, there was no significant increase in serum TT4 after the administration of rhTSH. Results of this study suggest that rhTSH could be a good substitute for bovine TSH, when used by the intravenous route, for the TSH stimulation test in dogs. Further studies are required to confirm its clinical usefulness.

Replication of the genome of human papillomaviruses (HPV) is initiated by the recruitment of the viral E1 helicase to the origin of DNA replication by the viral E2 protein, which binds specifically to the origin. We determined, for HPV type 11 (HPV-11), that the C-terminal 296 amino acids of E1 are sufficient for interaction with the transactivation domain of E2 in the yeast two-hybrid system and in vitro. This region of E1 encompasses the ATP-binding domain. Here we have examined the role of this ATP-binding domain, and of ATP, on E2-dependent binding of E1 to the origin. Several amino acid substitutions in the phosphate-binding loop (P loop), which is implicated in binding the triphosphate moiety of ATP, abolished E2 binding, indicating that the structural integrity of this domain is essential for the interaction. The structural constraints imposed on the E1 P loop may differ between HPV-11 and bovine papillomavirus type 1 (BPV-1), since the P479S substitution that inactivates BPV-1 E1 is tolerated in the HPV-11 enzyme. Other substitutions in the E1 P loop, or in two other conserved motifs of the ATP-binding domain, were tolerated, indicating that ATP binding is not essential for interaction with E2. Nevertheless, ATP-Mg stimulated the E2-dependent binding of E1 to the origin in vitro. This stimulation was maximal at the physiological temperature (37 degrees C) and did not require ATP hydrolysis. In contrast, ATP-Mg did not stimulate the E2-dependent binding to the origin of an E1 protein containing only the C-terminal domain (353 to 649) or that of mutant E1 proteins with alterations in the DNA-binding domain. These results are discussed in light of a model in which the E1 ATP-binding domain is required for formation of the E2-binding surface and can, upon the binding of ATP, facilitate and/or stabilize the interaction of E1 with the origin.