Timed up and go demonstrates strong interrater agreement and criterion validity as a functional test in geriatric dogs.

OBJECTIVE: To measure interobserver agreement for 4 functional tasks and their summed geriatric functional score (GFS) and correlate tasks and GFS with client-specific outcome measurements (CSOMs): Canine Brief Pain Inventory (CBPI) pain severity, CBPI pain interference, and Liverpool Osteoarthritis in Dogs. ANIMALS: 89 geriatric dogs were recruited between April and September 2023 from staff, friends, and clients of the Cornell University College of Veterinary Medicine with a median age of 11.0 years and weight of 26.4 kg. METHODS: Dogs underwent 4 sequential functional tests: timed up and go (TUG), cavallettis, figure 8s, and down to stands. Two observers independently scored each dog. The GFS was calculated based on the summed scores of the individual tests. Additional information collected included signalment, weight, measurements reflecting the comorbidities of aging (body condition score and muscle condition score), and CSOMs. RESULTS: Strong interrater agreement was found for all functional tests. The TUG in seconds (sTUG) and figure 8s demonstrated significant (P < .05) moderate to strong correlations to all CSOMs. The GFS showed similar significant correlations with all CSOMs except CBPI pain severity; however, when correlating individual tests to CSOMs, only figure 8s and TUG were significantly contributing to GFS results. Receiver operating characteristic curve analysis defined highly functional dogs as those completing the sTUG in under 3.83 seconds. The sTUG represented the best test for geriatric function given it was objective, reliable, correlated well to CSOMs, and could help identify highly functioning dogs. CLINICAL RELEVANCE: The sTUG appears to be the first practical and reliable functional test of canine geriatric mobility.

ATP-release pannexin channels are gated by lysophospholipids.

Adenosine triphosphate (ATP) serves as an extracellular messenger that mediates diverse cell-to-cell communication. Compelling evidence supports that ATP is released from cells through pannexins, a family of heptameric large pore-forming channels. However, the activation mechanisms that trigger ATP release by pannexins remain poorly understood. Here, we discover lysophospholipids as endogenous pannexin activators, using activity-guided fractionation of mouse tissue extracts combined with untargeted metabolomics and electrophysiology. We show that lysophospholipids directly and reversibly activate pannexins in the absence of other proteins. Molecular docking, mutagenesis, and single-particle cryo-EM reconstructions suggest that lysophospholipids open pannexin channels by altering the conformation of the N-terminal domain. Our results provide a connection between lipid metabolism and ATP signaling, both of which play major roles in inflammation and neurotransmission. One-Sentence Summary: Untargeted metabolomics discovers a class of messenger lipids as endogenous activators of membrane channels important for inflammation and neurotransmission.

Serum myostatin decreases in exercising and aging Alaskan sled dogs, while growth and differentiation factor 15 remains unaltered.

OBJECTIVES: To evaluate the serum concentrations of myostatin and growth and differentiation factor 15 (GDF-15) in Alaskan Husky sled dogs participating in a 350-mile (560-km) race and in an older population, and to examine correlations between changes in serum concentrations and body condition scores (BCSs). ANIMALS: Dogs were recruited from 3 teams of Alaskan Huskies participating in the Alaskan-Yukon Quest sled-dog race and retirees from a research sled-dog colony. PROCEDURES: Serum samples and BCSs were collected prior to racing, midway, and postrace; and in an older cohort (13 to 14 years). Myostatin and GDF-15 concentrations were assessed using commercially available ELISA kits. RESULTS: The median myostatin prerace concentration (9,519 pg/mL) was significantly greater than the mid- and postrace concentrations (7,709 pg/mL and 3,247 pg/mL, respectively). The prerace concentration was also significantly greater than that of the retired sled group dogs at 6,134 pg/mL. GDF-15 median serum concentrations did not change significantly across any racing time point (approx 350 pg/mL) or in the older cohort. No significant correlations were observed between changes in BCS and myostatin or GDF-15 concentrations. CLINICAL RELEVANCE: Serum myostatin decreases dramatically, yet no correlations to loss of BCS could be found. Myostatin signaling may be involved in maintaining hypertrophic signaling during intense exercise. Neither racing distance nor geriatric/retirement status appears to have an effect on serum GDF-15 concentration. Myostatin was less in the older, retired sled dogs compared to the younger racing cohort. Such differences highlight the roles that fitness level and age play regarding myostatin levels.

Assessment of Sex, Age, and Metabolism Relationships to Serum Thyroid Concentrations in Retired Alaskan Husky Sled Dogs.

Sled dogs are purpose-bred dogs selected for endurance work. Prior studies in racing dogs showed that serum thyroid parameters (total T4, free T4, and T3) are lower than the reference range in approximately 25% of dogs. Whether this is related to training, breeding, or body condition remains unclear. We hypothesized that retired sled dogs of normal body condition (9-13 years old) would have predominantly normal serum thyroid parameters and that serum thyroid status would be correlated to energy consumption based on metabolic body weight. Eighty-six sled dogs who were deemed healthy on physical exam, not on confounding medications, and without a prior diagnosis of hypothyroidism were included. All dogs' mean body condition scores were 5.1 ± 0.4 and body weight 24.5 ± 4.2 kg at fasting blood collection with stable dietary intake for 3 months before sampling. The total T4, free T4, and T3 serum concentrations were 23.4 ± 9.1 nmol/L, 9.53 ± 4.3 pmol/L, and 0.93 ± 0.39 nmol/L, respectively, with 38% lower than the reference range for total T4, 45% for free T4, and 37% for T3. All dogs were negative for thyroglobulin antibody, and TSH results were within normal ranges. Pearson's correlates based on kilocalories consumed on a metabolic body weight basis for total T4 (R = 0.14), free T4 (R = 0.01) and T3 (R = 0.23) showed poor correlation. No differences were observed between thyroid hormones and age, breed, or sex. Inactive, retired sled dogs can be misdiagnosed with hypothyroidism; therefore, our data suggests that misdiagnosis of hypothyroidism can occur and that the racing Alaskan sled dog has a unique reference range that should be considered when assessing serum thyroid status.

Canine Geriatric Rehabilitation: Considerations and Strategies for Assessment, Functional Scoring, and Follow Up.

Geriatric animals account for half of the pet population in the United States with their numbers increasing annually. Furthermore, a significant percentage of veterinary patients with movement limitations could be grossly categorized as geriatric and living within the end stage of their predicted lifespans. Because mobility is correlated to quality of life and time to death in aging dogs, a major goal in optimizing canine geriatric health is to improve functional movement. Within the geriatric population, identifying disabilities that affect daily living and quality of life may be used by the rehabilitation practitioner to provide stronger prognoses, treatment goals, and outcome measures. Examples of such means are described within this review. In human medicine, the concept of "optimal aging", or "healthy aging", has emerged in which inevitable detrimental age-related changes can be minimized or avoided at various levels of physical, mental, emotional, and social health. Both environment and genetics may influence aging. Identifying and improving environmental variables we can control remain a key component in optimizing aging. Furthermore, diagnosing and treating age related comorbidities common to older populations allows for improved quality of life and is often directly or indirectly affecting mobility. Obesity, sarcopenia, and a sedentary lifestyle are a trifecta of age-related morbidity common to both people and dogs. Healthy lifestyle choices including good nutrition and targeted exercise play key roles in reducing this morbidity and improving aging. Disablement models act as essential tools for creating more effective physiotherapy plans in an effort to counter dysfunction and disability. Within these models, functional testing represents a standard and validated means of scoring human geriatric function as well as monitoring response to therapy. Because of the great need in dogs, this review aims to provide a reasonable and testable standardized framework for canine functional scoring. We believe a complete assessment of canine geriatric patients should comprise of identifying environmental variables contributing to health status; diagnosing comorbidities related to disease and aging; and characterizing disability with standardized methods. Only through this process can we construct a comprehensive, reasonable, and targeted rehabilitation plan with appropriate follow up aimed at healthy aging.

Novel dry cryotherapy system for cooling the equine digit.

OBJECTIVES: Digital cryotherapy is commonly used for laminitis prophylaxis and treatment. Currently validated methods for distal limb cryotherapy involve wet application or compression technology. There is a need for a practical, affordable, dry cryotherapy method that effectively cools the digit. The objective of this study was to evaluate the hoof wall surface temperatures (HWSTs) achieved with a novel dry cryotherapy technology. DESIGN: Repeated-measures in vivo experimental study. SETTING: Experimental intervention at a single site. PARTICIPANTS: 6 systemically healthy horses (3 mares, 3 geldings). INTERVENTIONS: Cryotherapy was applied to six horses for eight hours with a commercially available rubber and rubber and welded fabricice boot, which extended proximally to include the foot and pastern. Reusable malleable cold therapy packs were secured against the foot and pastern with the three built-in hook-and-loop fastener panels. PRIMARY AND SECONDARY OUTCOME MEASURES: HWST and pastern surface temperature of the cryotherapy-treated limb, HWST of the control limb and ambient temperature were recorded every five minutes throughout the study period. RESULTS: Results were analysed with mixed-effects multivariable regression analysis. The HWST (median 11.1°C, interquartile range 8.6°C-14.7°C) in the cryotherapy-treated limb was significantly decreased compared with the control limb (median 29.7°C, interquartile range 28.9°C-30.4°C) (P≤0.001). Cryotherapy limb HWST reached a minimum of 6.75°C (median) with an interquartile range of 4.1°C-9.3°C. Minimum HWST was achieved 68 minutes after cryotherapy pack application. CONCLUSIONS: Dry application of cryotherapy significantly reduced HWST and reached minimums below the therapeutic target of 10°C. This cryotherapy method might offer an effective alternative for digital cooling.