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This canine in vivo study assessed the effect of recombinant human platelet-derived growth factor (rhPDGF) on the healing of periapical tissues following apical surgery. From a total of 96 premolar teeth, 64 teeth from six beagle dogs (2 years old) were classified as experimental and were randomly assigned to four experimental groups (16 teeth per group). After having the pulp extirpated, leaving teeth open to the oral cavity for 1 week, and sealing with an immediate restorative material for 8 weeks, nonsurgical endodontic treatment was performed. A split-mouth design was used, and intra-animal randomization of treatment sides was applied to the groups as follows: apical curettage + 1.5-mm root-end resection (Group 1); apicoectomy + mineral trioxide aggregate (MTA) root-end filling (Group 2); apicoectomy + MTA root-end filling + rhPDGF (Group 3); and apical curettage + rhPDGF (Group 4). The animals were sacrificed 24 months after apical surgery, and histologic and µCT analyses were performed for bone volume loss (BVL). Group 1 showed partial resolution of the periapical lesions without signs of tissue regeneration (BVL: 49.09 ± 10.97 mm3). Group 2 had minimal bone regeneration and showed cementum reformation in 9 teeth, with no direct attachment to the MTA (BVL: 35.34 ± 10.97 mm3). Group 3 showed regeneration of all damaged apical tissues without direct contact between the cementum and MTA (BLV: 4.51 ± 1.55 mm3). Group 4 showed regeneration of PDL, bone, and cementum and attachment of functional cementum fibers (BVL: 2.82 ± 2.3 mm3). The difference in BVL was statistically significant only for Groups 1 and 2 (P < .05). rhPDGF may help regenerate apical tissue structures following apical surgery. [ABSTRACT FROM AUTHOR]

For nonhuman primates living in anthropogenic areas, predation by larger predators is relatively rare. However, smaller predators, such as free-ranging as well as domesticated dogs, can shape the socioecology of urban nonhuman primates, either directly by attacking and killing them or indirectly by modifying their activity patterns. Here, we describe three (two probably fatal) cases of dog attacks on adult rhesus macaques inhabiting an anthropogenic landscape in Northern India and the circumstances surrounding these incidents. We discuss the importance of considering human presence and intervention in dog-nonhuman primate relationships while studying nonhuman primate populations across anthropogenic gradients, and its potential influences on group social dynamics and transmission of zoonotic agents.

BackgroundNatural killer (NK) cells are cytotoxic cells capable of recognizing heterogeneous cancer targets without prior sensitization, making them promising prospects for use in cellular immunotherapy. Companion dogs develop spontaneous cancers in the context of an intact immune system, representing a valid cancer immunotherapy model. Previously, CD5 depletion of peripheral blood mononuclear cells (PBMCs) was used in dogs to isolate a CD5dim-expressing NK subset prior to co-culture with an irradiated feeder line, but this can limit the yield of the final NK product. This study aimed to assess NK activation, expansion, and preliminary clinical activity in first-in-dog clinical trials using a novel system with unmanipulated PBMCs to generate our NK cell product.MethodsStarting populations of CD5-depleted cells and PBMCs from healthy beagle donors were co-cultured for 14 days, phenotype, cytotoxicity, and cytokine secretion were measured, and samples were sequenced using the 3'-Tag-RNA-Seq protocol. Co-cultured human PBMCs and NK-isolated cells were also sequenced for comparative analysis. In addition, two first-in-dog clinical trials were performed in dogs with melanoma and osteosarcoma using autologous and allogeneic NK cells, respectively, to establish safety and proof-of-concept of this manufacturing approach.ResultsCalculated cell counts, viability, killing, and cytokine secretion were equivalent or higher in expanded NK cells from canine PBMCs versus CD5-depleted cells, and immune phenotyping confirmed a CD3-NKp46+ product from PBMC-expanded cells at day 14. Transcriptomic analysis of expanded cell populations confirmed upregulation of NK activation genes and related pathways, and human NK cells using well-characterized NK markers closely mirrored canine gene expression patterns. Autologous and allogeneic PBMC-derived NK cells were successfully expanded for use in first-in-dog clinical trials, resulting in no serious adverse events and preliminary efficacy data. RNA sequencing of PBMCs from dogs receiving allogeneic NK transfer showed patient-unique gene signatures with NK gene expression trends in response to treatment.ConclusionsOverall, the use of unmanipulated PBMCs appears safe and potentially effective for canine NK immunotherapy with equivalent to superior results to CD5 depletion in NK expansion, activation, and cytotoxicity. Our preclinical and clinical data support further evaluation of this technique as a novel platform for optimizing NK immunotherapy in dogs.

The transmission of antimicrobial resistant bacteria in the urban environment is poorly understood. We utilized genomic sequencing and phylogenetics to characterize the transmission dynamics of antimicrobial resistant Escherichia coli (AMR-Ec) cultured from putative canine (caninep) and human feces present on urban sidewalks in San Francisco, California. We isolated a total of fifty-six AMR-Ec isolates from human (n = 20) and caninep (n = 36) fecal samples from the Tenderloin and South of Market (SoMa) neighborhoods of San Francisco. We then analyzed phenotypic and genotypic antimicrobial resistance (AMR) of the isolates, as well as clonal relationships based on cgMLST and single nucleotide polymorphisms (SNPs) of the core genomes. Using Bayesian inference, we reconstructed the transmission dynamics between humans and caninesp from multiple local outbreak clusters using the marginal structured coalescent approximation (MASCOT). Our results provide evidence for multiple sharing events of AMR-Ec between humans and caninesp. In particular, we found one instance of likely transmission from caninesp to humans as well as an additional local outbreak cluster consisting of one caninep and one human sample. Based on this analysis, it appears that non-human feces act as an important reservoir of clinically relevant AMR-Ec within the urban environment for this study population. This work showcases the utility of genomic epidemiology to reconstruct potential pathways by which antimicrobial resistance spreads.

Phonatory instabilities and involuntary register transitions can occur during singing. However, little is known regarding the mechanisms which govern such transitions. To investigate this phenomenon, we systematically varied laryngeal muscle activation and airflow in an in vivo canine larynx model during phonation. We calculated voice range profiles showing average nerve activations for all combinations of fundamental frequency (F0) and sound pressure level (SPL). Further, we determined closed-quotient (CQ) and minimum-posterior-area (MPA) based on high-speed video recordings. While different combinations of muscle activation favored different combinations of F0 and SPL, in the investigated larynx there was a consistent region of instability at about 400 Hz which essentially precluded phonation. An explanation for this region may be a larynx specific coupling between sound source and subglottal tract or an effect based purely on larynx morphology. Register transitions crossed this region, with different combinations of cricothyroid and thyroarytenoid muscle (TA) activation stabilizing higher or lower neighboring frequencies. Observed patterns in CQ and MPA dependent on TA activation reproduced patterns found in singers in previous work. Lack of control of TA stimulation may result in phonation instabilities, and enhanced control of TA stimulation may help to avoid involuntary register transitions, especially in the singing voice.

Genome-wide association studies (GWAS) in long-lived human populations have led to identification of variants associated with Alzheimer's disease and cardiovascular disease, the latter being the most common cause of mortality in people worldwide. In contrast, naturally occurring cancer represents the leading cause of death in pet dogs, and specific breeds like the Golden Retriever (GR) carry up to a 65% cancer-related death rate. We hypothesized that GWAS of long-lived GRs might lead to the identification of genetic variants capable of modifying longevity within this cancer-predisposed breed. A GWAS was performed comparing GR dogs ≥ 14 years to dogs dying prior to age 12 which revealed a significant association to ERBB4, the only member of the epidermal growth factor receptor family capable of serving as both a tumor suppressor gene and an oncogene. No coding variants were identified, however, distinct haplotypes in the 5'UTR were associated with reduced lifespan in two separate populations of GR dogs. When all GR dogs were analyzed together (n = 304), the presence of haplotype 3 was associated with shorter survival (11.8 years vs. 12.8 years, p = 0.024). GRs homozygous for haplotype 3 had the shortest survival, and GRs homozygous for haplotype 1 had the longest survival (11.6 years vs. 13.5 years, p = 0.0008). Sub-analyses revealed that the difference in lifespan for GRs carrying at least 1 copy of haplotype 3 was specific to female dogs (p = 0.009), whereas survival remained significantly different in both male and female GRs homozygous for haplotype 1 or haplotype 3 (p = 0.026 and p = 0.009, respectively). Taken together, these findings implicate a potential role for ERBB4 in GR longevity and provide evidence that within-breed canine lifespan studies could serve as a mechanism to identify favorable or disease-modifying variants important to the axis of aging and cancer.

Recent literature suggests that service dogs may be a valuable complementary intervention option for posttraumatic stress disorder (PTSD) among military veterans due to the potential influence on stress response dysregulation. The aim of this short-term longitudinal study was to quantify the impact of service dogs in US military veterans with PTSD with particular attention to the cortisol awakening response. A sub aim of the study was to empirically evaluate the physiological effects of PTSD service dogs on veteran partners. We conducted a clinical trial (ID: NCT03245814) that assessed the cortisol awakening response for 245 participants at baseline and 3 months follow-up across an intervention group (service dog: veterans n = 88, partners n = 46) and control group (usual care: n = 73, partners n = 38). A total of N = 161 veterans and N = 84 partners collected whole saliva samples via a passive drool collection immediately upon waking, 30 min after waking, and 45 min after waking on three consecutive weekdays at baseline and again at follow-up. Mixed model repeated measures (MMRM) with a fixed effect of the intervention group (service dog or control) were utilized. Covariates considered for the model included time of awakening, sleep duration, sleep efficiency, prior day experiences (measured via ecological momentary assessment), traumatic brain injury, age, gender, race, ethnicity, socioeconomic status, smoking status, alcohol use, physical health, and body mass index. A total of 3951 salivary samples were collected (veterans: 2613, partners: 1338). MMRM results demonstrated that veterans with a service dog had a statistically significant higher cortisol awakening response, including the area under the curve with respect to both increase (AUCi, β = 1.46, p = 0.046) and absolute increase (AINC, β = 0.05, p = 0.035). Results were not statistically significant for partners. Findings suggest that veterans with service dogs have a higher, less blunted CAR in comparison to veterans receiving usual care alone. In veterans with a blunted morning cortisol response, service dog placement could help boost their morning cortisol response.

Idiopathic epilepsy (IE) has been known to be inherited in the Belgian Tervuren for many decades. Risk genotypes for IE in this breed have recently been identified on Canis familiaris chromosomes (CFA) 14 and 37. In the current study, the allele frequencies of these loci were analyzed to determine whether dog breeders had employed a purposeful selection against IE, leading to a reduction in risk-associated allele frequency within the breed over time. The allele frequencies of two generational groupings of Belgian Tervuren with and without IE were compared. Allele frequencies for risk-associated alleles on CFA14 were unchanged between 1985 and 2015, whereas those on CFA37 increased during that time in the control population (p < 0.05). In contrast, dogs with IE showed a decrease (p < 0.05) in the IE risk-associated allele frequency at the CFA37 locus. Seizure prevalence in the Belgian Tervuren appears to be increasing. These results suggest that, despite awareness that IE is inherited, selection against IE has not been successful.

This study evaluated the tolerability and efficacy of the topical rho-kinase inhibitor netarsudil for canine primary corneal endothelial degeneration (PCED). Twenty-six eyes of 21 client-owned dogs with PCED were enrolled in a prospective, randomized, vehicle control clinical trial and received topical netarsudil 0.02% (Rhopressa®) or vehicle control twice daily (BID) for the first 4 months. Then, all patients received netarsudil for the next 4 or 8 months. Complete ophthalmic examination, ultrasonic pachymetry, Fourier-domain optical coherence tomography, and in vivo confocal microscopy were performed at baseline and 1, 2, 4, 6, 8 and 12 months. Effect of netarsudil on central corneal thickness (CCT), percentage of cornea with edema, and endothelial cell density (ECD) were evaluated by repeated measures ANOVA. Kaplan-Meier curves and log-rank test were used to compare corneal edema and clinical progression of eyes in netarsudil versus vehicle control groups. All dogs developed conjunctival hyperemia in at least one eye while receiving netarsudil. Unilateral transient reticulated intraepithelial bullae and stromal hemorrhage were observed respectively in 2 dogs in the netarsudil group. Two dogs showed persistently decreased tear production while receiving netarsudil, requiring topical immunomodulatory treatment. No significant differences in CCT, ECD, corneal edema or clinical progression were observed between netarsudil or vehicle treated eyes. When comparing efficacy of topical netarsudil BID and topical ripasudil 0.4% administered four times daily from our previous study, dogs receiving ripasudil had significantly less progression than those receiving netarsudil.

BACKGROUND: Fibrocartilaginous embolic myelopathy (FCE) is a well-documented condition in dogs although rarely reported in chondrodystrophic breeds. Genetic associations have not been defined. OBJECTIVES: Define the association of the chondrodystrophy-associated FGF4L2 retrogene with histopathologically confirmed cases of FCE. ANIMALS: Ninety-eight dogs with a histopathologic diagnosis of FCE. METHODS: Retrospective multicenter study. Dogs were genotyped for the FGF4L2 and FGF4L1 retrogenes using DNA extracted from formalin-fixed, paraffin-embedded tissue. Associations between breed, FCE and retrogene status were investigated with reference to a hospital population and known breed and general population allele frequencies. RESULTS: FGF4L2 genotype was defined in 89 FCE cases. Fibrocartilaginous embolic myelopathy was present in 22 dogs from FGF4L2-segregating breeds with allele frequencies of ≥5%; however, all dogs were wild type. Two Labrador retrievers with FCE carried FGF4L2 alleles. Frequency of the FGF4L2 allele was significantly (P

BACKGROUND: Giardia duodenalis (Gd) causes intestinal parasitosis. The involvement of the intestinal microbiome in determining the infections clinical phenotype is unknown. OBJECTIVE: Investigate the fecal microbiome features in dogs with giardiasis. ANIMALS AND METHODS: Cross-sectional study, including fecal samples of kenneled dogs with Gd diagnosed by fecal Giardia antigen dot ELISA. The fecal microbial compositional characteristics and dysbiosis index (DI) were compared between diarrheic and nondiarrheic dogs. RESULTS: Fecal samples of 38 Gd-infected dogs (diarrheic, 21; nondiarrheic, 17) were included. No differences were found in Faiths phylogenic diversity and beta diversity (weighted UniFrac distances) and in specific taxa abundances at the phylum, genus, and species levels, as well as in alpha and beta diversities between diarrheic and nondiarrheic dogs, and also when divided by sex or age. Among diarrheic dogs, alpha diversity was higher in males than in females (pairwise Kruskal-Wallis, q = 0.01). Among males, fecal abundances of the genus Clostridium (W = 19) and Clostridium spiroforme species (W = 33) were higher in diarrheic compared to nondiarrheic dogs. In diarrheic dog fecal samples, Proteobacteria were more prevalent (W = 1), whereas Verrucomicrobia were less prevalent in dogs

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is currently the leading cause of chronic liver disease worldwide. Metabolic Dysfunction-Associated Steatohepatitis (MASH), an advanced form of MASLD, can progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Based on recent findings by our team that liver 5HT2A knockout male mice suppressed steatosis and reduced fibrosis-related gene expression, we developed a peripheral 5HT2A antagonist, compound 11c for MASH. It shows good in vitro activity, stability, and in vivo pharmacokinetics (PK) in rats and dogs. Compound 11c also shows good in vivo efficacy in a diet-induced obesity (DIO) male mice model and in a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) male mice model, effectively improving histologic features of MASH and fibrosis. According to the tissue distribution study using [14C]-labeled 11c, the compound was determined to be a peripheral 5HT2A antagonist. Collectively, first-in-class compound 11c shows promise as a therapeutic agent for the treatment of MASLD and MASH.

Diabetes mellitus (DM) is a common chronic metabolic disease in humans and household cats that is characterized by persistent hyperglycemia. DM is associated with dysfunction of the intestinal barrier. This barrier is comprised of an epithelial monolayer that contains a network of tight junctions that adjoin cells and regulate paracellular movement of water and solutes. The mechanisms driving DM-associated barrier dysfunction are multifaceted, and the direct effects of hyperglycemia on the epithelium are poorly understood. Preliminary data suggest that fenofibrate, An FDA-approved peroxisome proliferator-activated receptor-alpha (PPARα) agonist drug attenuates intestinal barrier dysfunction in dogs with experimentally-induced DM. We investigated the effects of hyperglycemia-like conditions and fenofibrate treatment on epithelial barrier function using feline intestinal organoids. We hypothesized that glucose treatment directly increases barrier permeability and alters tight junction morphology, and that fenofibrate administration can ameliorate these deleterious effects. We show that hyperglycemia-like conditions directly increase intestinal epithelial permeability, which is mitigated by fenofibrate. Moreover, increased permeability is caused by disruption of tight junctions, as evident by increased junctional tortuosity. Finally, we found that increased junctional tortuosity and barrier permeability in hyperglycemic conditions were associated with increased protein kinase C-α (PKCα) activity, and that fenofibrate treatment restored PKCα activity to baseline levels. We conclude that hyperglycemia directly induces barrier dysfunction by disrupting tight junction structure, a process that is mitigated by fenofibrate. We further propose that counteracting modulation of PKCα activation by increased intracellular glucose levels and fenofibrate is a key candidate regulatory pathway of tight junction structure and epithelial permeability.

Ancestral Coast Salish societies in the Pacific Northwest kept long-haired woolly dogs that were bred and cared for over millennia. However, the dog wool-weaving tradition declined during the 19th century, and the population was lost. In this study, we analyzed genomic and isotopic data from a preserved woolly dog pelt from Mutton, collected in 1859. Mutton is the only known example of an Indigenous North American dog with dominant precolonial ancestry postdating the onset of settler colonialism. We identified candidate genetic variants potentially linked with their distinct woolly phenotype. We integrated these data with interviews from Coast Salish Elders, Knowledge Keepers, and weavers about shared traditional knowledge and memories surrounding woolly dogs, their importance within Coast Salish societies, and how colonial policies led directly to their disappearance.

ObjectiveDetermine diagnostic yield of chest, abdomen, and 4-site screening to diagnose metastatic disease and secondary diseases of prognostic significance in dogs with oral cancer.SampleMedical records from 381 dogs with histologically confirmed oral tumors that underwent preoperative screening were retrospectively reviewed.ResultsThoracic metastasis was diagnosed in 4.9% (0.9% odontogenic, 6.5% nonodontogenic) of oral tumors. Oral malignant melanoma and multilobular osteochondrosarcoma were most at risk. Abdominal metastasis was diagnosed in 2% of oral tumors (0% odontogenic, 3.1% nonodontogenic) and cytologically confirmed in 2 cases (0.6% [2/295)] of all abdominal ultrasounds (AUS) 5.5% [2/36] of all AUS that had cytology). Both cases had oral malignant melanoma. Incidental disease was diagnosed in 53.1% and 81.3% of thoracic and abdominal screenings, respectively. Major findings were more common in AUS (7.8%) compared to thoracic screening (1.9%). The prevalence of incidental findings was similar for odontogenic and nonodontogenic tumors. Both metastasis and major findings were diagnosed more commonly with thoracic CT compared to radiographs. Metastasis or a major finding of prognostic significance was diagnosed in at least 1 test in 27.8% of patients that had head CT, lymph node cytology, thoracic screening, and AUS (n = 115).Clinical relevanceMajor incidental findings were more commonly detected with AUS and were diagnosed in 1 in every 12 patients. However, metastatic disease was most commonly detected with thoracic screening. When all 4 screening tests are performed, there is an approximately 1 in 4 chance of diagnosing metastasis or major significant disease regardless of tumor type.

ObjectiveDetermine locoregional diagnostic yield of 4-site screening (head, neck, chest, and abdomen) to diagnose metastatic disease or clinically significant comorbid diseases in dogs with oral cancer.Animals381 dogs with histologically confirmed oral tumors.MethodsMedical records from 381 dogs with histologically confirmed oral tumors that underwent preoperative screening were retrospectively reviewed.ResultsSkull and neck CT scan was performed on 348 patients. Bone lysis was present in 74.4% of tumors. Oral squamous cell carcinoma, sarcomas, and T2-T3 (> 2 cm) tumors had a significantly (P < .05) increased incidence of lysis compared to odontogenic and T1 (< 2 cm) tumors, respectively. Minor incidental findings were present in 60.6% of CT scans. Major incidental findings were found in 4.6% of scans. The risk of diagnosing an incidental finding increased by 10% and 20% per year of age for minor and major findings, respectively. Lymph node metastasis was diagnosed with CT or cytology in 7.5% of cases (10.7% of nonodontogenic tumors, 0% of odontogenic tumors). Oral malignant melanoma, oral squamous cell carcinoma, and T3 tumors had the highest prevalence of metastatic disease at the time of staging. The presence of bone lysis was not associated with cervical metastasis.Clinical relevanceMajor incidental findings were rare (< 5%) but primarily included secondary extraoral tumors. Lymphatic metastasis was diagnosed in 10.7% of nonodontogenic tumors, but cytology was not performed in the majority of cases and often included only a single mandibular node. Therefore, these results likely underestimate the incidence of lymphatic metastasis. Guided lymph node sampling is highly recommended, especially for oral malignant melanoma, squamous cell carcinoma, and T2-T3 tumors.

Dynamic lower airway obstruction is the primary component of canine bronchomalacia, but the ventilatory function remains underinvestigated. This prospective study analyzed tidal breathing characteristics in 28 dogs, comprising 14 with severe bronchomalacia diagnosed by bronchoscopy versus 14 without respiratory disease. Spirometry was conducted in all dogs. Bronchoscopy with bronchoalveolar lavage or brush under anesthesia was performed in 14 dogs with cough and expiratory effort. Severe bronchomalacia was defined by the severity of collapse and total number of bronchi affected. Ventilatory characteristics were compared between groups. Results revealed that dogs with severe bronchomalacia had lower minute volume (218 vs 338 mL/kg, p = .039) and greater expiratory-to-inspiratory time ratio (1.55 vs 1.35, p = .01) compared to control dogs. The tidal breathing pattern of dogs with bronchomalacia was different from that of normal dogs, and the pattern differed from the concave or flat expiratory curves typical of lower airway obstruction. Compared to control dogs, dogs with severe bronchomalacia had a significantly prolonged low-flow expiratory phase (p < .001) on the flow-time plot and a more exponential shape of the expiratory curve (p < .001) on the volume-time plot. Flow-time index ExpLF/Te (>0.14) and volume-time index Vt-AUCexp (≤31%) had a high ROC-AUC (1.00, 95% confidence interval 0.88 to 1.00) in predicting severe bronchomalacia. In conclusion, the tidal breathing pattern identified here indicates abnormal and complicated ventilatory mechanics in dogs with severe bronchomalacia. The role of this pulmonary functional phenotype should be investigated for disease progression and therapeutic monitoring in canine bronchomalacia.

Purpose: To compare bone substitutes composed of glycated collagen with synthetic micro-sized (1 to 10 µm) hydroxyapatite (OB) vs non-cross-linked collagen matrix with large-particle (250 to 1,000 µm) bovine-derived hydroxyapatite (BOC). Materials and Methods: The P1 to P4 premolars were bilaterally extracted from the mandibles of 19 Beagle dogs. After 21 days, osteotomies were created in each dog that received OB or BOC and were covered with a collagen membrane or were left untreated. The animals were randomly divided into three groups based on sacrifice time (4, 12, or 24 weeks). The right and left hemimandibles were trimmed to facilitate imaging and histology, and all tissues were placed in 10% neutral-buffered formalin. Microcomputed tomography (MicroCT 40 Scanner, Scanco) was used to analyze bone sections. Bone volume, residual material volume, and bone mineral density were determined for each treatment site (OB and BOC) based on a volume of interest that encompassed the original defect. Additionally, blinded histopathologic assessment (based on the ISO 10993-6 scoring system) and histomorphometry were performed on sections ground to < 100 µm thick and stained with Stevenel's blue. Results: No clinical side effects were noted. No statistical differences were observed for OB vs BOC regarding the mineral volume percentage. Compared to OB, BOC had significantly higher mean mineralization densities at 12 weeks (P < .01), but this difference did not extend to 24 weeks. For residual grafting material, bone maturation, alveolar ridge restoration, and inflammatory response, OB showed a residual amount of bone graft and no statistical differences compared to BOC. Conclusion: Both OB and BOC represent valid treatment options for critically sized bone defects. Both bone fillers outperformed the sham-operated, ungrafted (empty) control, demonstrating statistically improved bone growth and ridge restoration. [ABSTRACT FROM AUTHOR]

The transcription factor hypoxia-inducible factor 1α (HIF-1α) drives metabolic reprogramming in gliomas (GLs) under hypoxic conditions, promoting glycolysis for tumor development. Evofosfamide (EVO) releases a DNA-alkylating agent within hypoxic regions, indicating that it may serve as a hypoxia-targeted therapy. The aim of this study was to investigate the glycolytic metabolism and antitumor effects of EVO in a canine GL model. Our clinical data showed that overall survival was significantly decreased in GL dog patients with higher HIF-1α expression compared to that of those with lower HIF-1α expression, and there was a positive correlation between HIF-1α and pyruvate dehydrogenase kinase 1 (PDK1) expression, suggesting that glycolytic activity under hypoxia conditions may contribute to poor outcomes in canine GL. Our glycolysis assay tests showed that the glycolytic ATP level was higher than the mitochondrial ATP level in three types of canine GL cell lines by activating the HIF-1 signal pathway under hypoxia conditions, resulting in an overall increase in total cellular ATP production. However, treatment with EVO inhibited the glycolytic ATP level in the GL cell lines under hypoxia conditions by targeting HIF-1α-positive cells, leading to decrease in total cellular ATP production. Our in vivo tests showed that EVO significantly reduced tumor development compared to controls and temozolomide in murine GL models. A metabolic analysis demonstrated that EVO effectively suppressed glycolytic metabolism by eliminating HIF-1α-positive cells, suggesting that it may restore metabolism in canine GLs. The evidence presented here supports the favorable preclinical evaluation of EVO as a potential improvement in cancer metabolism.

NK cells are a key focus in immuno-oncology, based on their ability to eliminate malignant cells without prior sensitization. Dogs are valuable models for translational immunotherapy studies, especially for NK cells, where critical species differences exist between mice and humans. Given that the mechanism for recognition of "self" by canine NK cells is currently unknown, we sought to evaluate expression of Ly49 in canine NK cells using in silico and high-throughput techniques. We interrogated the identified polymorphism/mutation in canine Ly49 and assessed the potential impact on structure using computational modeling of three-dimensional protein structure and protein-protein docking of canine Ly49 with MHC class I (MHC-I). Bulk and single-cell RNA-sequencing analysis was performed to detect gene expression of Ly49/KLRA1 in resting and activated NK cells. Tertiary protein structure demonstrated significant structural similarity to the known murine system. Molecular docking of canine Ly49 with MHC-I was favorable, converging at a single low-energy conformation. RNA sequencing revealed expression of Ly49/KLRA1 in both resting and activated NK cells and demonstrated almost exclusive expression of the gene in the NK cluster at the single-cell level. Despite prior reports of a mutated, nonfunctional canine Ly49, our data support that the protein product is predicted to bind to MHC-I in a comparable conformation to the murine system and is expressed in canine NK cells with upregulation following activation. Taken together, these data suggest that Ly49 is capable of recognizing MHC-I and therefore regulating NK cell function in dogs.

Salmonella infection causes epidemic death in wild songbirds, with potential to spread to humans. In February 2021, public health officials in Oregon and Washington, USA, isolated a strain of Salmonella enterica serovar Typhimurium from humans and a wild songbird. Investigation by public health partners ultimately identified 30 illnesses in 12 states linked to an epidemic of Salmonella Typhimurium in songbirds. We report a multistate outbreak of human salmonellosis associated with songbirds, resulting from direct handling of sick and dead birds or indirect contact with contaminated birdfeeders. Companion animals might have contributed to the spread of Salmonella between songbirds and patients; the outbreak strain was detected in 1 ill dog, and a cat became ill after contact with a wild bird. This outbreak highlights a One Health issue where actions like regular cleaning of birdfeeders might reduce the health risk to wildlife, companion animals, and humans.

OBJECTIVE: To describe a case of 5-hydroxytryptophan (5-HTP) toxicity successfully treated with haemodialysis in a dog. CASE SUMMARY: A 3-year-old, male neutered Labrador Retriever, weighing 28.2 kg, presented to the emergency department approximately 4-5 h after ingesting a human supplement containing 200 mg of 5-HTP. The amount of 5-HTP ingested was estimated between 980 and 1988 mg (35-71 mg/kg). At presentation, the dog demonstrated progressive neurologic abnormalities consistent with serotonin syndrome, including altered mentation and ataxia. Due to the magnitude of the ingested dose and progression of clinical signs, extracorporeal blood purification with intermittent haemodialysis was chosen to expedite clearance of 5-HTP. High-efficiency haemodialysis was initiated, and the dog showed continued clinical improvement throughout the 5-h treatment. Clinical signs resolved completely within 12 h. Sequential blood and urine samples were obtained to document levels of both 5-HTP and serotonin. The dog was discharged 24 h after presentation with complete resolution of clinical signs. NEW OR UNIQUE INFORMATION: This is the first report documenting the serial changes in 5-HTP concentrations during treatment with haemodialysis.

A 3-year-old male pit bull terrier was presented for a 4-day history of progressive tetraparesis and cervical pain. Magnetic resonance imaging confirmed an extradural mass within the left lateral vertebral canal extending from caudal C5 to mid-T2. Lumbar cerebrospinal fluid (CSF) demonstrated marked (90%) eosinophilic inflammation. A C6-7 dorsal laminectomy and C7-T2 left hemilaminectomy were done, with gross disease remaining. Histopathology revealed a large T cell lymphoma with marked eosinophilic infiltration. The dog underwent CHOP-based chemotherapy with resolution of clinical signs, with a similar course of therapy performed at recurrence 37 months after initial presentation. The dog was euthanized 39 months after presentation for multiorgan failure secondary to neutropenic sepsis and aspiration pneumonia. This represents a positive long-term response to multimodal treatment of extradural T-cell lymphoma within the vertebral canal associated with a marked CSF eosinophilia.

How does the similarity between stimuli affect our ability to learn appropriate response associations for them? In typical laboratory experiments learning is investigated under somewhat ideal circumstances, where stimuli are easily discriminable. This is not representative of most real-life learning, where overlapping stimuli can result in different rewards and may be learned simultaneously (e.g., you may learn over repeated interactions that a specific dog is friendly, but that a very similar looking one isnt). With two experiments, we test how humans learn in three stimulus conditions: one best case condition in which stimuli have idealized and highly discriminable visual and semantic representations, and two in which stimuli have overlapping representations, making them less discriminable. We find that, unsurprisingly, decreasing stimuli discriminability decreases performance. We develop computational models to test different hypotheses about how reinforcement learning (RL) and working memory (WM) processes are affected by different stimulus conditions. Our results replicate earlier studies demonstrating the importance of both processes to capture behavior. However, our results extend previous studies by demonstrating that RL, and not WM, is affected by stimulus distinctness: people learn slower and have higher across-stimulus value confusion at decision when stimuli are more similar to each other. These results illustrate strong effects of stimulus type on learning and demonstrate the importance of considering parallel contributions of different cognitive processes when studying behavior.

The importance of secure human attachments in childhood for healthy psychological development is well-established, yet the well-being implications of child-dog symbiotic relationships are less understood. Children form strong emotional bonds with their pet dogs that meet the prerequisites for an attachment relationship. These bonds can be mutually reinforcing and beneficial and could indicate positive child well-being. However, not all child-dog relationships are positive and here we explore whether harmful and unsafe interactions are associated with poorer emotional and behavioural functioning. The aim of this study was to examine whether the type of child-dog behaviour (positive or negative) mediates the relationship between child-dog attachment and well-being indicators. Data from caregiver reports (N = 117) and child self-reports (N = 77) were collected through an online survey. The results revealed that positive child-dog interactions significantly mediated the relationship between high attachment scores and better child outcomes (higher scores for well-being, positive outlook, happiness, quality of life, higher social satisfaction, and lower loneliness), whereas the reverse was found for negative child-dog interactions, predicting lower attachment scores and worse child outcomes (negative outlook, increased loneliness and social dissatisfaction, lower quality of life). This study has identified important mechanisms through which pet dogs may pose both benefits and risks to children’s psychological well-being. These findings will aid the development and evaluation of interventions that promote positive and safe child-dog interactions and subsequent child and dog psychological health and welfare.

Long-term use of sodium oxybate (SXB), (also called gamma-hydroxybutyrate [GHB]) attenuates the cataplexy and sleepiness of human narcolepsy. We had previously found that chronic opiate usage in humans and long-term opiate administration to mice significantly increased the number of detected hypocretin/orexin (Hcrt) neurons, decreased their size, and increased Hcrt level in the hypothalamus. We also found that opiates significantly decreased cataplexy in human narcoleptics as well as in narcoleptic mice and that cessation of locus coeruleus neuronal activity preceded and was tightly linked to cataplectic attacks in narcoleptic dogs. We tested the hypothesis that SXB produces changes similar to opiates and now report that chronic SXB administration significantly increased the size of Hcrt neurons, the reverse of what we had seen with opiates in humans and mice. Levels of Hcrt in the hypothalamus were nonsignificantly lower, in contrast to the significant increase in hypothalamic Hcrt level after opiates. SXB decreased tyrosine hydroxylase levels in the locus coeruleus, the major descending projection of the hypocretin system, also the reverse of what we saw with opioids. Therefore despite some similar effects on narcoleptic symptomatology, SXB does not produce anatomical changes similar to those elicited by opiates. Analysis of changes in other links in the cataplexy pathway might further illuminate SXBs mechanism of action on narcolepsy.

The lack of optimal models to evaluate novel agents is delaying the development of effective immunotherapies against human breast cancer (BC). In this prospective open label study, we applied neoadjuvant intratumoral immunotherapy with empty cowpea mosaic virus-like particles (eCPMV) to 11 companion dogs diagnosed with canine mammary cancer (CMC), a spontaneous tumor resembling human BC. We found that two neoadjuvant intratumoral eCPMV injections resulted in tumor reduction in injected tumors in all patients and in noninjected tumors located in the ipsilateral and contralateral mammary chains of injected dogs. Tumor reduction was independent of clinical stage, tumor size, histopathologic grade, and tumor molecular subtype. RNA-seq-based analysis of injected tumors indicated a decrease in DNA replication activity and an increase in activated dendritic cell infiltration in the tumor microenvironment. Immunohistochemistry analysis demonstrated significant intratumoral increases in neutrophils, T and B lymphocytes, and plasma cells. eCPMV intratumoral immunotherapy demonstrated antitumor efficacy without any adverse effects. This novel immunotherapy has the potential for improving outcomes for human BC patients.

Purpose: To determine the optimal implant diameter under limited bone width by comparing the effects of implants with different diameters on implant stability, peri-implant bone stability, and osseointegration. In addition, to evaluate the reliability of resonance frequency analysis (RFA) in detecting osseointegration and marginal bone level (MBL). Materials and Methods: Mandibular premolars and first molars of seven beagle dogs were extracted. After 8 weeks, their mandibular models and radiographic information were collected to fabricate implant templates. Implant sites were randomly divided into three groups according to diameter: Ø3.3, Ø4.1, and Ø4.8 mm. Implant stability quotient (ISQ) measurement and radiographic evaluation were performed after surgery (baseline) and at 4, 8, and 12 weeks. Three dogs were euthanized at 4 weeks to observe osteogenesis and implant-tissue interface biology. Four dogs were euthanized at 12 weeks to observe osseointegration. Hard tissue sections were prepared to analyze osteogenesis (fluorescence double labeling) and osseointegration (methylene blue-acid fuchsin staining). Results: At baseline and at 4, 8, and 12 weeks, the ISQ values of Ø4.1- and Ø4.8-mm implants did not differ (P > .05), but both had higher values than the Ø3.3-mm implants (P < .05). The mean marginal bone resorption (MBR) associated with Ø3.3-, Ø4.1-, and Ø4.8-mm implants was 0.65 ± 0.58 mm, 0.37 ± 0.28 mm, and 0.73 ± 0.37 mm, respectively. The buccal MBR of Ø4.8-mm implants was significantly higher than that of Ø4.1-mm implants (P < .05). The bone-to-implant contact (BIC) percentage at 12 weeks did not differ for any group (P > .05). The correlation coefficients between the ISQ and MBL of the Ø3.3-, Ø4.1-, and Ø4.8-mm implants were -0.84 (P < .01), -0.90 (P < .001), and -0.93 (P < .001), respectively, while that between the ISQ and BIC was 0.15 (P > .05). Conclusions: During the early healing stage, the performance of Ø4.1- and Ø4.8-mm implants in terms of implant stability was better than that of Ø3.3-mm implants. Implant diameter may not influence BIC percentage. RFA can be used to evaluate implant stability and MBL but is not suitable to assess the degree of osseointegration. [ABSTRACT FROM AUTHOR]

Purpose: To assess the literature comparing histologic levels of osseointegration for titanium vs zirconia dental implants. Materials and Methods: This systematic review was conducted following the PRISMA guidelines and was registered in PROSPERO (CRD42021236781). Electronic and manual searches were carried out through the PubMed/MEDLINE, PubMed Central, and Embase databases with a platform-specific search strategy combining controlled terms (MeSH and Emtree) and text words. The articles were selected by two independent investigators who evaluated the articles based on the criteria for eligibility. Results: A total of 17 articles were included. All were preclinical studies. The populations included dogs (27.55%), minipigs (14.28%), rats (14.28%), and rabbits (43.89%); and the implantation site varied among the mandible (36.82%), maxilla (9.04%), tibia (17.64%), skull (10.70%), and femur (25.80%). A total of 370 titanium (Ti) implants and 537 zirconia (Zr) implants were evaluated. The average osseointegration (% bone-to-implant contact) for Zr was 55.51% (17.6% to 89.09%), and for Ti was 58.50% (23.2% to 87.85%). There was no statistical difference between studies at the 2-month follow-up (P = .672), but this difference was significant at 1 and 3 months (P < .001). Conclusions: Within the limitations of this review, Zr implants had a similar level of osseointegration compared to Ti implants. Nonetheless, because these findings are based on preclinical research, all data must be carefully examined. [ABSTRACT FROM AUTHOR]

BackgroundAwareness of prescribing practices helps identify opportunities to improve antibiotic use (AU).ObjectivesTo estimate AU prevalence in dogs and cats in U.S. veterinary teaching hospitals (VTHs) and identify antibiotic drugs commonly prescribed, indications for use, and evidence of bacterial infection.AnimalsMedical record data were collected from dogs and cats examined at 14 VTHs.MethodsData were collected from VTH medical records of dogs and cats examined by primary care, urgent care, emergency and critical care, internal medicine, and surgery services on a single day during August 13-September 3, 2020. Data included signalment; clinical service; inpatient or outpatient status; clinical conditions; diagnostic tests; evidence of bacterial infection; intended reason for AU; name and route of antibiotics prescribed.ResultsOf 883 dogs and cats, 322 (36.5%) were prescribed at least 1 antibiotic. Among 285 antibiotics administered systemically intended for treatment of infection, 10.9% were prescribed without evidence of infection. The most common class of antibiotics presribed for systemic administration was potentiated penicillin for dogs (115/346, 33.3%) and cats (27/80, 33.8%). For dogs and cats, first-generation cephalosporins (93/346, 26.9% and 11/80, 13.8%, respectively) and fluoroquinolones (51/346, 14.7% and 19/80, 23.8%, respectively) was second or third most-prescribed. Common AU indications included skin, respiratory, and urinary conditions, and perioperative use.Conclusions and clinical importanceCollaborative data collection provides a sustainable methodology to generate national AU prevalence estimates and bring attention to areas requiring additional research and detailed data collection. These efforts can also identify practice improvement opportunities in settings where future veterinarians are trained.

The number of identified human polyomaviruses (HPyVs) has increased steadily over the last decade. Some of the novel HPyVs have been shown to cause disease in immunocompromised individuals. The Lyon-IARC polyomavirus (LIPyV) belonging to species Alphapolyomavirus quardecihominis was identified in 2017 in skin and saliva samples from healthy individuals. Since its initial discovery, LIPyV has rarely been detected in human clinical samples but has been detected in faeces from cats with diarrhoea. Serological studies show low LIPyV seroprevalence in human populations. To investigate the possibility that LIPyV is a feline rather than a human polyomavirus, we compared serum IgG responses against the VP1 major capsid protein of LIPyV and 13 other HPyVs among cats (n = 40), dogs (n = 38) and humans (n = 87) using an in-house immunoassay. Seropositivity among cats was very high (92.5%) compared to dogs (31.6%) and humans (2.3%). Furthermore, the median antibody titres against LIPyV were 100-10,000x higher in cats compared to dogs and humans. In conclusion, the high prevalence and intensity of measured seroresponses suggest LIPyV to be a feline rather than a human polyomavirus. Whether LIPyV infection induces diarrhoea or other symptoms in cats remains to be established.

Experiences of positive affect (PA) are common when interacting with animals and may help to build resilience. This study explored how children’s relationships with pet dogs, parents, and friends are related to their experiences of PA with their pet dog. In addition, we examined whether greater PA with pet dogs was related to children’s thriving. The sample (n = 115, 57 girls, 58 boys) included children 9–14 years of age who reported the quality of relationships with their pet dog (Positive Relationship Qualities, Friction, Pets as Substitutes), attachment security to parents, and positive and negative friendship quality. PA was assessed with child self-report before and after interacting with their dog, observed child and dog PA during the interaction, and reports of daily PA when interacting with the dog from a 7-day daily log. Children completed questionnaires to assess attachment security relationship with parents and friendship relationship quality. Children’s relationships with parents and friends were related to PA in the interaction session, whereas relationships with pet dogs, parents, and friends were all related to the daily experiences of PA. Children’s experiences of PA in daily interactions with pet dogs, parent-child attachment, and positive friendship quality were all related to children’s thriving. The findings suggest that experiences of PA may be one mechanism that accounts for the effects of animals on children’s development.

The neurosteroid allopregnanolone (ALLO) is under investigation as a treatment for benzodiazepine-refractory status epilepticus (SE). Here, we assess the cardiopulmonary safety of intravenous ALLO by itself and after a clinically recommended dose of midazolam (MDZ) in two healthy adult beagles. Each dog received ALLO (1 mg/kg, IV), and after a washout period of 2 weeks, each dog was dosed with MDZ (0.2 mg/kg, IV) followed 10 minutes later by ALLO. Behavioral state, vital signs, arterial blood gases, blood chemistries, and plasma ALLO concentrations were monitored for up to 6 hours after dosing. The dogs appeared sleepy but were fully responsive after both treatments. No depression of mean arterial pressure or respiratory rate was noted. Blood gas measurements failed to show evidence of drug-induced acute respiratory acidosis. Estimated maximum plasma ALLO concentrations were in the range of 1500 to 3000 ng/ml. The results indicate that intravenous ALLO can be used safely to treat benzodiazepine-refractory SE, even when administered shortly after a benzodiazepine.

This study assessed the histologic and histomorphometric changes of free gingival grafts in a canine model after mechanical expansion. A total of eight epithelialized tissue samples were obtained from the palate of eight Beagle dogs. Samples were cut in half and separated into two groups: the test group, in which a device was used to expand the grafts, and the control group, without expansion. After histologic processing, samples were evaluated by qualitative histology and histomorphometry. Histologic analysis revealed some differences in epithelial cell morphology and keratin layer integrity in the test group compared to the control group. Differences in histomorphometric parameters for the expanded and nonexpanded groups, including the thickness of the keratin layer (15.4 ± 13.4 µm and 32.3 ± 18.1 µm, respectively), thickness of the epithelium (398.0 ± 168.0 µm and 368.4 ± 142.8 µm, respectively), and the area occupied by collagen fibers in the connective tissue (62.0% ± 11.0% and 55.8% ± 7.6%, respectively), were not statistically significant (P > .05). Despite some changes in qualitative histology, free gingival grafts maintained their histomorphometric characteristics after mechanical expansion. These data provide a scientific basis for the use of mechanical expansion as a possible procedure to reduce the morbidity of autogenous grafts because a single soft tissue sample can be expanded before grafting. [ABSTRACT FROM AUTHOR]

Background: Myxomatous mitral valve disease (MMVD) is the most common acquired cardiovascular disease in small breed dogs. In contrast to human patients with heart failure (HF), iron deficiency (ID) prevalence in dogs with MMVD is weakly known. The study aimed to assess the usability of ID markers in serum and reticulocyte parameters from whole blood of dogs with MMVD to evaluate early ID symptoms. Results: Sixty-eight dogs (43 male and 25 female) were included in the study. MMVD dogs were assigned according to the 2019 ACVIM guidelines for groups B1 (n = 9), B2 (n = 10), C (n = 27) and D (n = 10). Groups were also combined into B1 and B2 as non-symptomatic HF and C with D as symptomatic HF. Healthy controls were 12 dogs. Serum iron concentration below the reference range in dogs with MMVD was 12.5%. Other ID indices, such as %SAT, UIBC, and TIBC were similar in the MMVD groups and healthy controls (p > 0.05 for all parameters). Statistical comparison between control group and 4 groups of different stages of MMVD showed that significant differences occur only in serum transferrin. The assessment of ferritin and soluble transferrin receptors using Western Blotting did not show differences between control (n = 7) and MMVD (n = 33) dogs. Study has shown positive correlation between ID parameters and echocardiographic indices such as LA/Ao and LVIDdN, and some biochemical parameters. A significant increase in reticulocytes percentage, assessed manually, was observed in the HF group of animals (p = 0.027) compared to the control group. Conclusions: Studies have shown that ID parameters in serum are not significantly different in dogs with MMVD compared to healthy dogs. However, there is a clear correlation between atrial size and normalised left ventricular size to body size and some biochemical parameters, including ID parameters and therefore the severity of MMVD. [ABSTRACT FROM AUTHOR]

Canine leishmaniosis, caused by the protozoan parasite Leishmania infantum, is a cosmopolitan vector-borne zoonosis, transmitted principally by Phlebotomus perniciosus in Spain and Portugal, where it is considered an endemic disease. Ecoinformatics tools such as ecological niche models (ENM) have been successfully tested to model the distribution of the risk of infection of different parasitosis as they take into account environmental variables vital for their survival. The risk map proposed in this study combines the potential distribution of Ph. perniciosus in the Iberian Peninsula and the calculation of the infection rate of the parasite in the vector to model the risk of contracting the disease in a more realistic way. In fact, this weighting strategy improves the predictive power of the resulting model (R² = 0.42, p = < 0.01) compared to the Ph. perniciosus ENM model alone (R² = 0.13, p > 0.05). The places with the highest risk of transmission are the southwest and central peninsular area, as well as the Mediterranean coast, the Balearic Islands and the Ebro basin, places where the ideal habitat of Ph. perniciosus and the infection rate is also high. In the case of future projections under climate change scenarios, an increase in the risk of infection by L. infantum can be observed in most of the territory (4.5% in 2040, 71.6% in 2060 and 63% in 2080), mainly in the northern part of the peninsula. The use of ENMs and their weighting with the infection rate in Ph. perniciosus is a useful tool in predicting the risk of infection for L. infantum in dogs for a given area. In this way, a more complete model can be obtained to facilitate prevention and control. [ABSTRACT FROM AUTHOR]

In a recent study (doi: 10.1371/journal.pone.0265662), associations were identified between owner-reported dog health status and diet, whereby those fed a vegan diet were perceived to be healthier. However, the study was limited because it did not consider possible confounding from variables not included in the analysis. The aim of the current study was to extend these earlier findings, using different modelling techniques and including multiple variables, to identify the most important predictors of owner perceptions of dog health. From the original dataset, two binary outcome variables were created: the 'any health problem' distinguished dogs that owners perceived to be healthy ("no") from those perceived to have illness of any severity; the 'significant illness' variable distinguished dogs that owners perceived to be either healthy or having mild illness ("no") from those perceived to have significant or serious illness ("yes"). Associations between these health outcomes and both owner-animal metadata and healthcare variables were assessed using logistic regression and machine learning predictive modelling using XGBoost. For the any health problem outcome, best-fit models for both logistic regression (area under curve [AUC] 0.842) and XGBoost (AUC 0.836) contained the variables dog age, veterinary visits and received medication, whilst owner age and breed size category also featured. For the significant illness outcome, received medication, veterinary visits, dog age and were again the most important predictors for both logistic regression (AUC 0.903) and XGBoost (AUC 0.887), whilst breed size category, education and owner age also featured in the latter. Any contribution from the dog vegan diet variable was negligible. The results of the current study extend the previous research using the same dataset and suggest that diet has limited impact on owner-perceived dog health status; instead, dog age, frequency of veterinary visits and receiving medication are most important. [ABSTRACT FROM AUTHOR]

Aims Methods and Results Conclusions To estimate the prevalence of carbapenemase‐producing Enterobacterales (CPE) carriage among pets using faecal specimens submitted to veterinary diagnostic laboratories throughout the US. A secondary aim was to employ whole‐genome sequencing (WGS) to characterize isolates of CPE from companion animals and compare them to publicly available CPE genomes.To estimate the prevalence of CPE in companion animals in the USA, a multicenter surveillance study including 8 different veterinary diagnostic laboratories from across the USA was conducted. Briefly, remnant faecal specimens from dogs and cats were screened using two selective agar plates (CHROMID Carba and MacConkey with 1 mg/L cefotaxime and 0.125 mg/L meropenem) and presumptive CPE isolates screened by the modified carbapenemase inactivation method for carbapenemase production. A total of 2393 specimens were screened and yielded 196 isolates for carbapenemase screening. A total of 5 isolates from 4 dogs and 1 cat at 3 different veterinary diagnostic laboratories were confirmed to produce a carbapenemase (0.21%). Whole‐genome sequencing (WGS) revealed two E. coli (ST167) isolates that both produced an NDM‐5 carbapenemase, two Enterobacter hormaechei (ST171) isolates that produced an NDM‐5 carbapenemase and a KPC‐4 carbapenemase respectively and one Klebsiella oxytoca (ST199) that produced an Oxa‐48‐type carbapenemase. Both E. coli isolates were found to be within at least 22 SNPs of previously characterized canine and human CPE isolates.This study demonstrates that the prevalence of CPE among companion animals is relatively low (0.21%) but that given the genetic relatedness of animal isolates to human isolates, additional surveillance is needed. [ABSTRACT FROM AUTHOR]

In the left axilla of a formalin-embalmed adult female cross-breed dog, an unusual course of the axillary artery in relation to the brachial plexus was noted. A part of the axillary artery after the origin of the subscapular artery coursed through the loop formed by the contributions of the caudal pectoral and lateral thoracic nerves and then between the median and ulnar nerves. Thus, the common trunk for the latter two nerves was missing. Instead, in the proximal brachium, they communicated with each other in both directions. A communicating branch between the cranial and caudal pectoral nerves forming a nerve loop, ansa pectoralis lacked the axillary artery and was instead traversed by the subscapular artery. This is a variation in the relationship between the axillary artery and brachial plexus in the domestic dog and has not been reported in the literature yet. The axillary artery entrapped by the contributions of the caudal and lateral thoracic nerves may be considered as a risk factor for the neuroarterial compressions with non-specific signs and should be taken into account both in surgery and imaging. [ABSTRACT FROM AUTHOR]