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Canines represent a valuable model for mammalian aging studies as large animals with short lifespans, allowing longitudinal analyses within a reasonable time frame. Moreover, they develop a spectrum of aging-related diseases resembling that of humans, are exposed to similar environments, and have been reasonably well studied in terms of physiology and genetics. To overcome substantial variables that complicate studies of privately-owned household dogs, we have focused on a more uniform population composed of retired Alaskan sled dogs that shared similar lifestyles, including exposure to natural stresses, and are less prone to breed-specific biases than a pure breed population. To reduce variability even further, we have collected a population of 103 retired (8-11 years-old) sled dogs from multiple North American kennels in a specialized research facility named Vaika. Vaika dogs are maintained under standardized conditions with professional veterinary care and participate in a multidisciplinary program to assess the longitudinal dynamics of aging. The established Vaika infrastructure enables periodic gathering of quantitative data reflecting physical, physiological, immunological, neurological, and cognitive decline, as well as monitoring of aging-associated genetic and epigenetic alterations occurring in somatic cells. In addition, we assess the development of age-related diseases such as arthritis and cancer. In-depth data analysis, including artificial intelligence-based approaches, will build a comprehensive, integrated model of canine aging and potentially identify aging biomarkers that will allow use of this model for future testing of antiaging therapies.

The domestic canine (canis familiaris) is a growing novel model for human neuroscientific research. Unlike rodents and primates, they demonstrate unique convergent sociocognitive skills with humans, are highly trainable and able to undergo non-invasive experimental procedures without restraint, including fMRI. In addition, the gyrencephalic structure of the canine brain is more similar to that of human than rodent models. The increasing use of dogs for non-invasive neuroscience studies has generating a need for a standard canine cortical atlas that provides common spatial referencing and cortical segmentation for advanced neuroimaging data processing and analysis. In this manuscript we create and make available a detailed MRI-based cortical atlas for the canine brain. This atlas includes a population template generated from 30 neurologically and clinically normal non-brachycephalic dogs, tissue segmentation maps and a cortical atlas generated from Jerzy Kreiner's myeloarchitectonic-based histology atlas. The provided cortical parcellation includes 234 priors from frontal, sensorimotor, parietal, temporal, occipital, cingular and subcortical regions. The atlas was validated using an additional canine cohort with variable cranial conformations. This comprehensive cortical atlas provides a reference standard for canine brain research and will improve and standardize processing and data analysis and interpretation in functional and structural MRI research.

In human athletes significant changes in cytokine concentrations secondary to exercise have been observed. This prospective study evaluated the effect of a multi-day stage sled dog race on plasma concentrations of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10). Samples from 20 dogs were harvested prior to and on days 2 and 8 of an 8-day race. Exercise resulted in significantly decreased TNF-α and IL-8 as well as increases of MCP-1, IL-6, and IL-10 concentrations (P-value between 0.01 and < 0.0001 for all parameters). The proportion of values for IL-2 that were below the detection limit increased from 40% on day 0 to 75% on day 2 and decreased on day 8 to 40% (P = 0.04). Racing sled dogs show cytokine-concentration changes that are different from those in humans.

Glucagon plays a central role in amino acid (AA) homeostasis. The dog is an established model of glucagon biology, and recently, metabolomic changes in people associated with glucagon infusions have been reported. Glucagon also has effects on the kidney; however, changes in urinary AA concentrations associated with glucagon remain under investigation. Therefore, we aimed to fill these gaps in the canine model by determining the effects of glucagon on the canine plasma metabolome and measuring urine AA concentrations. Employing two constant rate glucagon infusions (CRI) - low-dose (CRI-LO: 3 ng/kg/min) and high-dose (CRI-HI: 50 ng/kg/min) on five research beagles, we monitored interstitial glucose and conducted untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) on plasma samples and urine AA concentrations collected pre- and post-infusion. The CRI-HI induced a transient glucose peak (90-120 min), returning near baseline by infusion end, while only the CRI-LO resulted in 372 significantly altered plasma metabolites, primarily reductions (333). Similarly, CRI-HI affected 414 metabolites, with 369 reductions, evidenced by distinct clustering post-infusion via data reduction (PCA and sPLS-DA). CRI-HI notably decreased circulating AA levels, impacting various AA-related and energy-generating metabolic pathways. Urine analysis revealed increased 3-methyl-l-histidine and glutamine, and decreased alanine concentrations post-infusion. These findings demonstrate glucagons glucose-independent modulation of the canine plasma metabolome and highlight the dogs relevance as a translational model for glucagon biology. Understanding these effects contributes to managing dysregulated glucagon conditions and informs treatments impacting glucagon homeostasis.

Background: Primary immune thrombocytopenia (pITP) in dogs presents a diagnostic challenge, and clinical markers of severity are lacking. Objectives: Identify clinicopathologic features that differentiate pITP from secondary ITP (sITP) and markers related to bleeding severity, transfusion, and survival of dogs with pITP. Animals: Ninety‐eight thrombocytopenic dogs (58 pITP and 40 sITP). Methods: Client‐owned dogs with platelet counts <50 000/μL were enrolled in a prospective, multi‐institution cohort study. History and treatment information, through a maximum of 7 days, was recorded on standard data forms. Bleeding severity was scored daily using a bleeding assessment tool (DOGiBAT). At‐admission blood samples were collected for CBC, biochemistry, C‐reactive protein concentration, and coagulation panels, and to measure platelet surface‐associated immunoglobulin G (PSAIg) and expression of platelet membrane proteins and phospholipids. Dogs with evidence of coincident disease were classified as sITP. Results: No definitive pITP diagnostic test was found. However, pITP cases were characterized by lower platelet counts, D dimer concentrations, and platelet membrane protein expression than sITP cases. Differentiation between pITP and sITP was further enhanced using logistic regression modeling combining patient sex, coagulation profile, platelet count, D dimer, and PSAIg. A second model of pITP severity indicated that low hematocrit and high BUN concentration were associated with non‐survival. Low hematocrit at admission, but not platelet count or DOGiBAT score, was associated with transfusion. Conclusions and Clinical Importance: Pending validation studies, models constructed from at‐admission clinicopathologic findings may improve differentiation of pITP from sITP and identify the most severe pITP cases at the time of presentation. [ABSTRACT FROM AUTHOR]

Background: The role of diet in the pathogenesis and treatment of chronic enteropathies (CE) in dogs is unresolved. Objectives: To compare the ability of diets composed of hydrolyzed fish, rice starch, and fish oil without (HF) or with prebiotics, turmeric, and high cobalamin (HF+) against a limited ingredient diet containing mixed nonhydrolyzed antigens and oils (control) to resolve clinical signs and maintain serum cobalamin and folate concentrations in dogs with nonprotein losing CE (non‐PLE). To determine the ability of hydrolyzed fish diets to support recovery and remission in dogs with PLE. Animals: Thirty‐one client‐owned dogs with CE: 23 non‐PLE, 8 PLE. Methods: Randomized, blinded, controlled trial. Diets were fed for 2 weeks; responders continued for 12 weeks. Nonresponders were crossed over to another diet for 12 weeks. Response was determined by standardized clinical evaluation with long‐term follow‐up at 26 weeks. Concurrent medications were allowed in PLE. Results: Nineteen of 23 (83%; 95% confidence interval [CI], 60%‐94%) non‐PLE CE responded clinically to their initial diet, with no difference between diets (P >.05). Four nonresponders responded to another diet, with sustained remission of 18/18 (100%; 95%CI, 78%‐100%) at 26 weeks. Serum cobalamin concentration was increased (P <.05) and maintained by diet. Serum folate concentration decreased posttreatment (P <.05) but was restored by dietary supplementation. Hydrolyzed fish diets supported weight gain, serum albumin concentration, and recovery (P <.05) in dogs with PLE. Conclusions and Clinical Importance: Changing diet, independent of antigen restriction or supplemental ingredients, induced long‐term remission in dogs with non‐PLE CE. Serum cobalamin and folate concentrations were maintained by diet. Hydrolyzed fish diets supported clinical recovery and remission in PLE. [ABSTRACT FROM AUTHOR]

Background: Praziquantel is the drug of choice for treating the tapeworm Dipylidium caninum in dogs; however, resistance is possible, and regular, non-targeted administration of praziquantel may select for anthelminthic-resistant populations. Methods: The zinc sulfate fecal floatation procedure was conducted. Gross visualization was used to identify Dipylidium spp. segments, and capsule endoscopy was used to visualize adult tapeworms within the intestinal tract. Results: An 18-month-old spayed female terrier mix was presented due to diarrhea, hematochezia and weight loss. The dog received appropriate anthelmintic therapy for Giardia spp., Ancylostoma spp. and Dipylidium spp. The dog's clinical signs resolved, and elimination of Ancylostoma spp. was confirmed by subsequent fecal analysis. However, Dipylidium spp. segments were repeatedly present in the stool. Observation of the segments confirmed the presence of adult Dipylidium spp in feces. Treatment with praziquantel and epsiprantel were unsuccessful in eliminating the organism but was apparently successful in flea prevention. A single dose of nitrosconate was administered and eliminated Dipylidium spp. infection in the dog. Conclusions: Nitrosconate can be an effective treatment for praziquantel-resistant dipylidiasis in dogs. The novel application of capsule endoscopy confirmed the anthelmintic efficacy of this treatment. [ABSTRACT FROM AUTHOR]

Background: Superficial necrolytic dermatitis (SND) in dogs is a rare disorder most commonly associated with hepatocutaneous syndrome. Although often reported as fatal, sporadically reported long‐term remissions might be more common than previously believed and linked to treatment regimens. Hypothesis/Objectives: Evaluate treatments and associated outcomes in dogs with hepatocutaneous‐associated hepatopathy (HCH) with or without SND, designated collectively aminoaciduric canine hypoaminoacidemic hepatopathy syndrome (ACHES). Animals Forty‐one dogs of various breeds and ages diagnosed with ACHES. Methods: Retrospective study. Electronic surveys, medical records (2014‐2019), and communication with veterinarians provided data. Three treatment categories were each dichotomized: IV amino acid (IV‐AA) infusions (≥2 vs <2), supplements including S‐adenosylmethionine (SAMe), arginine with ornithine, glutathione, lysine, proline, omega‐3 fatty acids, or zinc (≥3 vs <3), and diet type (home‐cooked vs commercial). Optimal treatment was defined as receiving ≥2 IV‐AA treatments, ≥3 nutritional supplements, and a home‐cooked diet. Results: Most dogs (29/41, 71%) received IV‐AA infusions (23/29, ≥2 infusions). Twenty‐one dogs (51%) were fed commercial diets; 17/41 (41%) were fed home‐cooked diets. Most dogs received SAMe (32/41, 78%) and a median of 3 supplements. In 4 dogs, HCH remission occurred. Overall all‐cause median survival time (MST) was 359 days, and disease‐specific MST was 557 days (range, 1‐1783 days). Optimally treated dogs (n = 9) lived significantly longer (MST, >1783 days, P =.02) than variably treated dogs (MST, 214 days). Conclusions and Clinical Importance: Optimized ACHES management can resolve SND and HCH and confer long‐term survival. [ABSTRACT FROM AUTHOR]

Background: Superficial necrolytic dermatitis (SND), hepatocutaneous‐associated hepatopathy (HCH), aminoaciduria, and hypoaminoacidemia define hepatocutaneous syndrome (HCS) in dogs. Dogs without SND but that possess all other syndrome components are not well described. Hypothesis/objectives: To define an inclusive syndrome, aminoaciduric canine hypoaminoacidemic hepatopathy syndrome (ACHES) for dogs with HCH or HCS. Compare clinical features, salient clinicopathologic variables, and plasma and urine amino acid (AA) profiles among ACHES cases by skin lesion status. Animals Dogs of various breeds and ages diagnosed with ACHES (n = 41). A control (CON) cohort (n = 12) provided AA profile data. Methods: Retrospective case series. Available medical records of previously identified cases were reviewed for salient clinical features and clinical pathology data. Plasma and urine AA profiles were performed. Cutaneous lesion status was classified as none, mild, or fulminant. Results: Thirty cases (73%) developed SND at some time. Dogs with fulminant skin lesions at diagnosis (n = 22/41, 54%) had significantly lower hematocrit (P =.05) and mean corpuscular volume (P =.01) than dogs without SND. Principal component analysis of plasma AA profiles identified distinct clustering of CON from ACHES dogs, but not by skin lesion status. Plasma 1‐methylhistidine (<7 nmol/mL) and cystathionine (<7.5 nmol/mL) were robust ACHES biomarkers. Urine lysine (>344 nmol/mg creatinine) and methionine (>68 nmol/mg creatinine) also were useful ACHES biomarkers. Conclusions and Clinical Importance: Specific AA biomarkers provide additional diagnostic utility in ACHES. Data suggests that HCH is an early stage, and SND a later stage manifestation of ACHES. [ABSTRACT FROM AUTHOR]

Background: Degenerative myelopathy (DM) in dogs is a progressive neurodegenerative condition that causes white matter spinal cord lesions. These lesions are undetectable on standard magnetic resonance imaging (MRI), limiting diagnosis and monitoring of the disease. Spinal cord lesions cause disruption to the structural integrity of the axons causing water diffusion to become more random and less anisotropic. These changes are detectable by the technique of diffusion tensor imaging (DTI) which is highly sensitive to diffusion alterations secondary to white matter lesion development. Objective: Perform spinal DTI on cohorts of dogs with and without DM to identify if lesions caused by DM will cause a detectable alteration in spinal cord diffusivity that correlates with neurological status. Animals Thirteen dogs with DM and 13 aged‐matched controls. Methods: All animals underwent MRI with DTI of the entire spine. Diffusivity parameters fractional anisotropy (FA) and mean diffusivity (MD) were measured at each vertebral level and statistically compared between groups. Results: Dogs with DM had significant decreases in FA within the regions of the spinal cord that had high expected lesion load. Decreases in FA were most significant in dogs with severe forms of the disease and correlated with neurological grade. Conclusions and Clinical Importance: Findings suggest that FA has the potential to be a biomarker for spinal cord lesion development in DM and could play an important role in improving diagnosis and monitoring of this condition. [ABSTRACT FROM AUTHOR]

B Correction: Parasites & Vectors (2022) 15:438 b https://doi.org/10.1186/s13071-022-05559-2 Following publication of the original article [[1]], the authors flagged errors in the reported doses of Lopatol® (nitrosconate): in the main body of the article, a 200 mg dose had been stated in place of 500 mg, the correct dose; in Table 1, a 100 mg/kg dose had been reported in place of a 50 mg/kg dose, the correct dose. Reference 1 Loftus JP, Acevedo A, Bowman DD, Liotta JL, Wu T, Zhu M. Elimination of probable praziquantel-resistant Dipylidium caninum with nitroscanate in a mixed-breed dog: a case report. [Extracted from the article]

Abstract: 5-Lipoxygenase cDNA was prepared from canine white blood cells revealing the full-length message using an oligonucleotide capping method. The sequenced 5-Lipoxygenase open reading frame revealed a 2031 base pair message encoding a 676 amino acid protein. The amino acid sequence showed mild variation with the presumed canine sequence, as well as differences in important residues of known phosphorylation observed in other species. The sequence had between 86 and 92% homology with other species, revealing a highly conserved sequence. Confirmation of gene product identity was achieved through transient transfection of the gene in a V5-Histidine tagged pcDNA 3.1 vector into a known canine cell line. Both V5 antibody and 5-lipoxygenase antibody confirmed the gene product using Western blotting and immunoflourescence. [Copyright &y& Elsevier]

OBJECTIVE To determine the clinical and analytical accuracy of a new veterinary-calibrated portable blood glucose monitor (PBGM) compared to a reference laboratory analyzer. ANIMALS Client-owned dogs (n = 77) and cats (n = 64). METHODS Peripheral and paired capillary whole-blood glucose concentrations measured via PBGM were compared to plasma glucose concentrations measured via a Cobas c501 reference analyzer (Roche). Analytical accuracy was evaluated with the Spearman rank correlation coefficient, Bland-Altman difference plot analysis, and Deming regression. Clinical accuracy was evaluated with Parkes error grid analysis. Paired peripheral and capillary blood samples were compared with the Wilcoxon matched-pairs signed-rank test. RESULTS There was a high correlation between PBGM and reference analyzer readings in dogs and cats. Human quality assurance standards (International Organization for Standardization 15197:2013 guidelines) for analytical accuracy were met for 95% of feline peripheral blood samples and 89% of canine samples. Similar veterinary standards (American Society of Veterinary Clinical Pathology guidelines) were met for 89% of canine and 92% of feline peripheral blood glucose measurements. Error grid analysis showed that all peripheral canine and 97% of feline measurements were clinically accurate (zone A). Any altered clinical decision for the remaining feline measurements was expected to minimally impact outcome (zone B). No significant difference was found between peripheral and capillary blood glucose measurements in either species. CLINICAL RELEVANCE The PBGM produced clinically accurate results and is suitable for use in veterinary and home settings to measure blood glucose. [ABSTRACT FROM AUTHOR]

OBJECTIVE To compare plasma concentrations of glucagon and glucagon-like peptide-1 (GLP-1) between healthy dogs and dogs with aminoaciduric canine hypoaminoacidemic hepatopathy syndrome (ACHES) dogs. ANIMALS Privately owned healthy (n = 5) control (CON) and ACHES (8; including 3 with diabetes mellitus) dogs enrolled between October 2, 2019, and March 4, 2020. PROCEDURES This was a prospective case-control study. Fasting and 15-minute postprandial plasma glucagon total GLP-1 concentrations were measured with commercial immunoassays. RESULTS Dogs with ACHES had lower fasting (median, 0.5; mean difference, 3.8; 95% CI, 0.52 to 7.0 pmol/L; P = .021) and postprandial (median, 0.35; mean difference, 5.0; 95% CI, 1.8 to 8.3 pmol/L; P = .002) plasma glucagon concentra- tions than CON (fasting and postprandial medians, 3.5 and 4.6 pmol/L, respectively). ACHES dogs had significantly (median, 4.15; mean difference, 12.65; 95% CI, 2.0 to 16.3 pg/ml; P = .011) lower postprandial plasma GLP-1 concen- trations than CON (median, 16.8 pg/ml). There was no significant difference between fasting GLP-1 levels between the 2 groups. CLINICAL RELEVANCE Lower postprandial plasma GLP-1 concentrations may contribute to the propensity of diabetes mellitus in ACHES. Lower glucagon concentrations may reflect an appropriate physiologic response to hypoaminoacidemia. [ABSTRACT FROM AUTHOR]