Effect of video angle on detection of induced front limb lameness in horses.

BACKGROUND: Lameness examinations are commonly performed in equine medicine. Advancements in digital technology have increased the use of video recordings for lameness assessment, however, standardization of ideal video angle is not available yielding videos of poor diagnostic quality. The objective of this study was to evaluate the effect of video angle on the subjective assessment of front limb lameness. A randomized, blinded, crossover study was performed. Six horses with and without mechanically induced forelimb solar pain were recorded using 9 video angles including horses trotting directly away and towards the video camera, horses trotting away and towards a video camera placed to the left and right side of midline, and horses trotting in a circle with the video camera placed on the inside and outside of the circle. Videos were randomized and assessed by three expert equine veterinarians using a 0-5 point scoring system. Objective lameness parameters were collected using a body-mounted inertial sensor system (Lameness Locator®, Equinosis LLC). Interobserver agreement for subjective lameness scores and ease of grading scores were determined. RESULTS: Induction of lameness was successful in all horses. There was excellent agreement between objective lameness parameters and subjective lameness scores (AUC of the ROC = 0.87). For horses in the "lame" trials, interobserver agreement was moderate for video angle 2 when degree of lameness was considered and perfect for video angle 2 and 9 when lameness was considered as a binary outcome. All other angles had no to fair agreement. For horses in the "sound" trials, interobserver agreement was perfect for video angle 5. All other video angles had slight to moderate agreement. CONCLUSIONS: When video assessment of forelimb lameness is required, a video of the horse trotting directly towards the video camera at a minimum is recommended. Other video angles may provide supportive information regarding lameness characteristics.

Estimation of glucose absorption, insulin sensitivity, and glucose effectiveness from the oral glucose tolerance test.

CONTEXT: Glucose tolerance during an oral glucose tolerance test (OGTT) is affected by variations in glucose effectiveness (GE) and glucose absorption and thus affects minimal model calculations of insulin sensitivity (SI). The widely used OGTT SI by Dalla Man et al. does not account for variances in GE and glucose absorption. OBJECTIVE: To develop a novel model that concurrently assesses SI, GE, and glucose absorption. DESIGN: Cross-sectional. SETTING: Academic Medical Center. PARTICIPANTS: Eighteen subjects without abnormalities on OGTT (controls) and 88 subjects with diabetes. INTERVENTION: All subjects underwent 75-gram 120-minute 6-timepoint OGTT. MAIN OUTCOMES: SI from the Dalla Man model was validated with the novel model Si using Bland Altman limits of agreement methodology. Comparisons of SI, GE, and gastrointestinal glucose half-life (GIGt1/2); a surrogate measure for glucose absorption were made between subjects with diabetes and controls. RESULTS: In controls and diabetes, the novel model SI was higher than the current OGTT model. SI from both controls (ƿ=0.90, p < 0.001) and diabetes (ƿ=0.77, p < 0.001) has high agreement between models. GE was higher in diabetes (median:0.021 1/min, IQR [interquartile range]: 0.020-0.022) compared to controls (median:0.016 1/min, IQR: 0.015-0.017), p = 0.02. GIGt1/2 was shorter in diabetes (median: 48.404 min, IQR: 54.424-39.426) than in controls (median: 55.086 min, IQR: 61.368-48.502) without statistical difference. CONCLUSIONS: Our novel model SI has a good correlation with SI from the widely used Dalla Man's model while concurrently calculating GE and GIGt1/2. Thus, besides estimating SI, our novel model can quantify differences in insulin-independent glucose disposal mechanisms important for diabetes pathophysiology.

Twenty-four hour continuous transvenous temporary right ventricular pacing in healthy horses.

BACKGROUND: The ability to perform transvenous temporary cardiac pacing (TV-TP) is critical to stabilize horses with symptomatic bradyarrhythmias. Reports of successful TV-TP in horses are limited, and only briefly describe short-term pacing. OBJECTIVE: To describe temporary, medium-term (24 h) transvenous right ventricular pacing in awake horses using a bipolar torque-directed pacing catheter. ANIMALS: Six healthy adult institutional teaching horses. METHODS: Prospective experimental study with 2 immediately successive TV-TP lead placements in each horse with a target location of the RV apex. One placement was performed primarily with echocardiographic guidance and 1 primarily with fluoroscopic guidance. In all placements, corresponding images were obtained with both imaging modalities. Horses were then paced for 24 h, unrestricted in a stall with continuous telemetric ECG monitoring. Echocardiographically determined lead position, episodes of pacing failure in the preceding 6 h, and pacing thresholds were recorded every 6 h. Pacing failure was defined as a period of loss of capture longer than 20 s. RESULTS: Pacing leads were placed with both guidance methods and maintained for 24 h with no complications. Two horses with leads angled caudally in the right ventricular apex had no pacing failure, the remaining 4 horses had varying degrees of loss of capture. Leads located in the right ventricular apex had longer time to pacing failure and lower capture thresholds P < 0.05. CONCLUSIONS AND CLINICAL IMPORTANCE: Medium-term TV-TP is feasible and has potential for stabilization of horses with symptomatic bradyarrhythmias. Lead position in the right ventricular apex appears optimal. Continuous ECG monitoring is recommended to detect pacing failure.

Evaluation of remote assistance for point-of-care ultrasonography in a large animal hospital: a controlled randomized trial.

OBJECTIVE: To assess whether remote assistance is beneficial to the accuracy of point-of-care ultrasound (POCUS) examinations during equine emergency evaluations. ANIMALS: Adult horses presenting to a tertiary care large animal emergency service for respiratory or gastrointestinal clinical signs. PROCEDURES: Prospective, randomized, controlled, clinical study. Cases were assigned to receive POCUS with remote assistance ("POCUS-R" group) or POCUS with no assistance ("POCUS" group). Accuracy of diagnosis, duration of sonograms and survival to discharge were the objective outcomes compared between groups. Perceptions about the use of teleultrasound were gathered using a survey. RESULTS: 29 cases were enrolled in the study over an 18-month period. Based on Cox regression estimates, sonogram duration was likely to be longer in the POCUS-R group (n = 13) relative to the POCUS group (16) hazard ratio 0.43 (95% CI, 0.9 to 0.2; P = .03). Whether the final diagnosis was included in the differential diagnosis list, number of diagnoses in the differential list and survival were not different between groups. Educational benefits were the most frequently mentioned benefit by clinician users while logistical and technical problems related to the use of the equipment and inconvenience of enrollment in the study was the most common negative aspect. CLINICAL RELEVANCE: Teleultrasound was generally not well adopted by users likely due to inconvenience and time constraints. Further work is indicated to assess differences in clinical outcomes in a setting that would allow a larger sample size to increase statistical power.

Early-phase insulin secretion during mixed-meal tolerance testing predicts ß-cell function and secretory capacity in cystic fibrosis.

Insulin secretion within 30 minutes of nutrient ingestion is reduced in people with cystic fibrosis (PwCF) and pancreatic insufficiency and declines with worsening glucose tolerance. The glucose potentiated arginine (GPA) test is validated for quantifying ß-cell secretory capacity as an estimate of functional ß-cell mass but requires technical expertise and is burdensome. This study sought to compare insulin secretion during mixed-meal tolerance testing (MMTT) to GPA-derived parameters in PwCF. Methods: Secondary data analysis of CF-focused prospective studies was performed in PwCF categorized as 1) pancreatic insufficient [PI-CF] or 2) pancreatic sufficient [PS-CF] and in 3) non-CF controls. MMTT: insulin secretory rates (ISR) were derived by parametric deconvolution using 2-compartment model of C-peptide kinetics, and incremental area under the curve (AUC) was calculated for 30, 60 and 180-minutes. GPA: acute insulin (AIR) and C-peptide responses (ACR) were calculated as average post-arginine insulin or C-peptide response minus pre-arginine insulin or C-peptide under fasting (AIRarg and ACRarg), ~230 mg/dL (AIRpot and ACRpot), and ~340 mg/dL (AIRmax and ACRmax) hyperglycemic clamp conditions. Relationships of MMTT to GPA parameters were derived using Pearson's correlation coefficient. Predicted values were generated for MMTT ISR and compared to GPA parameters using Bland Altman analysis to assess degree of concordance. Results: 85 PwCF (45 female; 75 PI-CF and 10 PS-CF) median (range) age 23 (6-56) years with BMI 23 (13-34) kg/m2, HbA1c 5.5 (3.8-10.2)%, and FEV1%-predicted 88 (26-125) and 4 non-CF controls of similar age and BMI were included. ISR AUC30min positively correlated with AIRarg (r=0.55), AIRpot (r=0.62), and AIRmax (r=0.46) and with ACRarg (r=0.59), ACRpot (r=0.60), and ACRmax (r=0.51) (all P<0.001). ISR AUC30min strongly predicted AIRarg (concordance=0.86), AIRpot (concordance=0.89), and AIRmax (concordance=0.76) at lower mean GPA values, but underestimated AIRarg, AIRpot, and AIRmax at higher GPA-defined ß-cell secretory capacity. Between test agreement was unaltered by adjustment for study group, OGTT glucose category, and BMI. Conclusion: Early-phase insulin secretion during MMTT can accurately predict GPA-derived measures of ß-cell function and secretory capacity when functional ß-cell mass is reduced. These data can inform future multicenter studies requiring reliable, standardized, and technically feasible testing mechanisms to quantify ß-cell function and secretory capacity.

Dorsal-to-palmar branch neuroanastomosis in horses undergoing palmar digital neurectomy does not reduce neuroma formation or improve outcome.

OBJECTIVE: Chronic foot pain, a common cause of forelimb lameness, can be treated by palmar digital neurectomy (PDN). Complications include neuroma formation and lameness recurrence. In humans, neuroanastomoses are performed to prevent neuroma formation. The aim of the study was to evaluate the outcome of horses undergoing dorsal-to-palmar branch neuroanastomosis following PDN. STUDY DESIGN: Retrospective case series. ANIMALS: Eighty-five horses with PDN and dorsal-to-palmar branch neuroanastomosis. METHODS: Medical records for horses undergoing this procedure at two hospitals between 2015 and 2020 were reviewed. Palmar and dorsal nerve branches of the PDN were transected and end-to-end neuroanastomosis was performed by apposition of the perineurium. Follow-up was obtained from medical records and telephone interviews. Success was defined as resolution of lameness for at least one year. RESULTS: Lameness resolved following surgery in 81/85 (95%) horses with 57/84 (68%) sound at one year. Postoperative complications occurred in 19/85 (22%) cases. The main limitations of the study were an incomplete data set, inaccurate owner recall, and variations in procedure. CONCLUSION: Compared to previous studies, this technique resulted in similar numbers of horses sound immediately after surgery, a comparable rate of postoperative neuroma formation but a higher recurrence of lameness rate at 1 year postoperatively. CLINICAL SIGNIFICANCE: End-to-end neuroanastomosis of the dorsal and palmar branches of the PDN does not reduce the rate of neuroma formation in horses. Long-term outcome was less favorable compared to previously reported PDN techniques.

A missed opportunity: A scoping review of the effect of sex and age on osteoarthritis using large animal models.

OBJECTIVE: The objective was to critically analyze the published literature accounting for sex differences and skeletal age (open vs. closed physis) in preclinical animal models of OA, including the disaggregation of data by sex and skeletal maturity when data is generated from combined sex and/or multi-aged cohorts without proper confounding. METHOD: A scoping literature review of PubMed, Web of Science, EMBASE, and SCOPUS was performed for studies evaluating the effect of sex and age in experimental studies and clinical trials utilizing preclinical large animal models of OA. RESULTS: A total of 9727 papers were identified in large animal (dog, pig, sheep, goat, horse) models for preclinical OA research, of which 238 ex vivo and/or in vivo studies disclosed model type, animal species, sex, and skeletal age sufficient to analyze their effect on outcomes. Dogs, followed by pigs, sheep, and horses, were the most commonly used models. A paucity of preclinical studies evaluated the effect of sex and age in large animal models of naturally occurring or experimentally induced OA: 26 total studies reported some kind of analysis of the effects of sex or age, with 4 studies discussing the effects of sex only, 11 studies discussing the effects of age only, and 11 studies analyzing both the effects of age and sex. CONCLUSION: Fundamental to translational research, OARSI is uniquely positioned to develop recommendations for conducting preclinical studies using large animal models of OA that consider biological mechanisms linked to sex chromosomes, skeletal age, castration, and gonadal hormones affecting OA pathophysiology and treatment response.

(Pro)renin receptor signaling in hypothalamic tyrosine hydroxylase neurons is required for obesity-associated glucose metabolic impairment.

Glucose homeostasis is achieved via complex interactions between the endocrine pancreas and other peripheral tissues and glucoregulatory neurocircuits in the brain that remain incompletely defined. Within the brain, neurons in the hypothalamus appear to play a particularly important role. Consistent with this notion, we report evidence that (pro)renin receptor (PRR) signaling within a subset of tyrosine hydroxylase (TH) neurons located in the hypothalamic paraventricular nucleus (PVNTH neurons) is a physiological determinant of the defended blood glucose level. Specifically, we demonstrate that PRR deletion from PVNTH neurons restores normal glucose homeostasis in mice with diet-induced obesity (DIO). Conversely, chemogenetic inhibition of PVNTH neurons mimics the deleterious effect of DIO on glucose. Combined with our finding that PRR activation inhibits PVNTH neurons, these findings suggest that, in mice, (a) PVNTH neurons play a physiological role in glucose homeostasis, (b) PRR activation impairs glucose homeostasis by inhibiting these neurons, and (c) this mechanism plays a causal role in obesity-associated metabolic impairment.

Measurement of 8-hydroxy-2'-deoxyguanosine in serum and cerebrospinal fluid of horses with neuroaxonal degeneration and other causes of proprioceptive ataxia.

BACKGROUND: Eight-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative damage evaluated in human neurodegenerative disease, has potential to correlate with postmortem diagnosis of neuroaxonal dystrophy/degenerative myeloencephalopathy (NAD/DM) in horses. HYPOTHESIS: We hypothesized that 8-OHdG will be higher in CSF and serum from NAD/DM horses compared with horses with other neurologic diseases (CVSM, EPM) and a control group of neurologically normal horses. We also hypothesized that 8-OHdG will be higher in CSF compared with serum from NAD/DM horses. ANIMALS: Fifty client-owned horses with postmortem diagnoses: 20 NAD/DM, 10 CVSM, 10 EPM, and 10 control horses. Serum and CSF samples were obtained between November 2010 and March 2022. METHODS: Case-control study using biobanked samples was performed and commercial competitive ELISA kit (Highly Sensitive 8-OHdG Check ELISA) utilized. Concentration of 8-OHdG was quantitated in both CSF and serum and compared between groups. RESULTS: No correlation was established between the measures of 8-OHdG in serum and CSF and group. CSF median [8-OHdG] for NAD/DM was 169.9 pg/mL (IQR25-75 : 67.18-210.6), CVSM 157.1 pg/mL (IQR25-75 : 132.1-229.1), EPM 131.4 pg/mL (IQR25-75 : 102.1-193.2), and control 149.8 pg/mL (IQR25-75 : 113.3-196.4). Serum median [8-OHdG] for NAD/DM was 130 pg/mL (IQR25-75 : 51.73-157.2), CVSM 125.8 pg/mL (IQR25-75 : 62.8-170.8), EPM 120.6 pg/mL (IQR25-75 : 87.23-229.7), and control 157.6 pg/mL (IQR25-75 : 97.15-245.6). Poisson regression analysis showed no difference established once confounding variables were considered. CONCLUSIONS: Eight-OHdG did not aid in antemortem diagnosis of NAD/DM in this cohort of horses. At the time of diagnosis horses with NAD/DM do not have ongoing oxidative stress.

Prospective, longitudinal assessment of subchondral bone morphology and pathology using standing, cone-beam computed tomography in fetlock joints of 2-year-old Thoroughbred racehorses in their first year of training.

BACKGROUND: Catastrophic injuries of the fetlock joints occur in Thoroughbred racehorses and are preceded by stress-induced bone injury. Early detection of subchondral bone injury is essential to prevent irreversible damage or bone failure. OBJECTIVES: To investigate the use of standing, robotic cone-beam computed tomography (CBCT) for assessing longitudinal changes in subchondral bone morphology and pathology of the fetlock joints associated with race training in young Thoroughbreds. STUDY DESIGN: Observational cohort study. METHODS: Forty-one 2-year-old Thoroughbred racehorses were recruited prior to the start of race training. Standing CBCT and radiographs of all 4 metacarpo-/metatarsophalangeal (MCP/MTP) joints were obtained at 0, 6 and 12 months. Hyperdensity, as an estimate of subchondral bone sclerosis, was measured in the distal third metacarpal (MC3)/metatarsal (MT3) bone and proximal phalanx (P1) at each time point on computed tomography. CBCTs were examined for subchondral bone pathology consisting of areas of hypodensity within regions of hyperdensity. RESULTS: Subchondral bone sclerosis increased significantly over time in the medial and lateral MC3/MT3 condyles and in the medial and lateral parasagittal grooves of MC3/MT3. The presence of subchondral bone pathology increased significantly over time in the medial and lateral palmar condyles of MC3/MT3, the lateral parasagittal groove, the medial dorsal condyle and the medial and lateral ridges of P1. MAIN LIMITATIONS: There was attrition of horses due to relocation, change in ownership, and retirement from racing. Husbandry, training regimens and racing schedules were not controlled for in the study. CONCLUSIONS: Standing CBCT is an efficient and effective screening tool for assessing subchondral bone morphology and identifying pathology of the fetlock joint in young Thoroughbred racehorses. CBCT may facilitate early detection of bone pathology allowing for timely intervention and prevention of more serious injuries.

The influence of different horseshoes and ground substrates on mid-stance hoof orientation at the walk.

BACKGROUND: Horseshoes with modified contact surfaces combined with deformable ground substrates are used to change hoof orientation during mid-stance, for example, for therapeutic reasons. OBJECTIVES: To measure the effect of horseshoes and ground substrates on sagittal and transverse plane hoof orientation at mid-stance using a dorsal hoof wall mounted triaxial accelerometer. STUDY DESIGN: In vivo experiment, randomised crossover design. METHODS: Differences in sagittal and transverse plane angles between standing and mid-stance of the left front hoof of six horses walking with regular horseshoes, egg bar, toe-wide, medial-wide, lateral-wide and three-degree egg bar shoes on turf, sand and hard ground substrates were assessed with linear mixed models with horseshoe and substrate type as fixed factors (p < 0.05) for each animal. RESULTS: Hoof angles were significantly affected by horseshoe (p < 0.001), surface (p < 0.001) and the combination (p < 0.001). The sagittal plane angle increased in deformable ground substrates at walk-in mid-stance on turf [mean (±standard deviation): 2.6° (±3.8°)] and on sand [2.6° (±4.1°)] across all shoes. The greatest increase was observed with egg bar shoes [turf: 4.37° (±3.82°); sand 4.69° (±3.83°)]. There was a tendency for the hoof to sink laterally into deformable ground substrates among all shoes [turf: 1.11° (±1.49°); sand: 0.93° (±1.93°)]. Medial-wide shoes increased the lateral sinking [turf: 2.00° (±1.63°); sand: 1.79° (±1.58°)]. Lateral-wide shoes reduced the lateral sinking on turf [0.62° (±1.26°)] and induced a marginal medial sinking on sand [-0.007° (±2.03°)]. MAIN LIMITATIONS: The substrate properties were not quantitatively assessed, and observations were limited to front hooves at the walk. A larger sample size would be preferable. CONCLUSIONS: Mid-stance hoof orientation changes with specific combinations of shoes and ground substrates in the walking horse.

CONTEXTO: É especulado que ferraduras com solados diferentes combinadas com superfícies deformáveis podem mudar a orientação do casco durante a fase de apoio, por exemplo, por razões terapêuticas. OBJETIVOS: Mensurar o efeito de diferentes ferraduras e superfícies na orientação do casco nos planos sagital e transversal durante a fase de apoio usando um acelerômetro triaxial acoplado à parte dorsal do casco. DELINEAMENTO DO ESTUDO: Experimento in vivo, delineamento randomizado e cruzado. MÉTODOS: As diferenças entre os ângulos dos planos sagital e transverso nas diferentes fases de apoio do casco do membro anterior esquerdo de seis cavalos ao passo utilizando ferradura normal, oval, oval talonada, de pinça larga e com extensão medial ou lateral na grama, areia ou superfície dura foram avaliadas utilizando modelos mistos lineares com ferradura e tipo de superfície como fatores fixos (P < 0.05) para cada animal. RESULTADOS: Os ângulos do casco foram significativamente afetados pelo tipo de ferradura (P < 0.001), superfície (P < 0.001) e pela combinação de ambos (P < 0.001). O ângulo do plano sagital aumentou em superfícies deformáveis no passo na fase de apoio na grama (média (+/­SD): 2.6 (+/−3.8) graus) e na areia (2.6 (+/−4.1 graus) para todos os tipos de ferradura. O maior aumento foi observado com a ferradura oval (grama: 4.37 (+/− 3.82) graus; areia 4.69 (+/−3.83) graus). Houve uma tendência de o casco rebaixar mais lateralmente em superfícies deformáveis com todas as ferraduras (grama: 1.11 (+/−1.49) graus; areia: 0.93 (+/−1.93) graus). Ferraduras com extensão medial aumentaram o rebaixamento lateral (grama: 2.00 (+/−1.63) graus; areia: 1.79 (+/−1.58) graus). Ferraduras com extensão lateral reduziram o rebaixamento lateral na grama (0.62 (+/−1.26) graus) e induziram o rebaixamento medial na areia (−0.007 (+/−2.03) graus). PRINCIPAIS LIMITAÇÕES: As propriedades das superfícies não foram avaliadas quantitativamente, e as observações foram limitadas aos cascos dos membros anteriores e ao passo. Um número maior de animais no estudo seria desejável. CONCLUSÕES: A orientação do casco na fase de apoio muda de acordo com combinações específicas de ferradura e superfícies no cavalo ao passo.

Use of multiple admission variables better predicts intestinal strangulation in horses with colic than peritoneal or the ratio of peritoneal:blood l-lactate concentration.

BACKGROUND: Early identification of strangulating obstruction (SO) in horses with colic improves outcomes, yet early diagnosis of horses requiring surgery for SO often remains challenging. OBJECTIVES: To compare blood and peritoneal fluid l-lactate concentrations, peritoneal:blood l-lactate ratio, peritoneal minus blood (peritoneal-blood) l-lactate concentration and other clinical variables for predicting SO and SO in horses with small intestinal lesions (SO-SI) and then to develop a multivariable model to predict SO and SO-SI. STUDY DESIGN: Retrospective cohort. METHODS: A total of 197 equids admitted to a referral institution for colic between 2016 and 2019 that had peritoneal fluid analysis performed at admission were included. Twenty-three admission variables were evaluated individually for the prediction of a SO or SO-SI and then using multivariable logistic regression. Odds ratios (ORs) with 95% confidence intervals (CI) and area under the curve of the receiver operator characteristic (AUC ROC) were calculated. RESULTS: All variables performed better in the model than individually. The final multivariable model for predicting SO included marked abdominal pain (OR 5.31, CI 1.40-20.18), rectal temperature (OR 0.30, CI 0.14-0.64), serosanguineous peritoneal fluid (OR 35.34, CI 10.10-122.94), peritoneal-blood l-lactate (OR 1.77, CI 1.25-2.51), and peritoneal:blood l-lactate ratio (OR 0.36, CI 0.18-0.72). The AUC ROC was 0.91. The final multivariable model for predicting SO-SI included reflux volume (OR 0.69, CI 0.56-0.86), blood l-lactate concentration (OR 0.43, CI 0.22-0.87), serosanguineous peritoneal fluid (OR 4.99, CI 1.26-19.74), and peritoneal l-lactate concentration (OR 3.77, CI 1.82-7.81). MAIN LIMITATIONS: Retrospective, single-hospital study design. CONCLUSIONS: Blood and peritoneal fluid l-lactate concentrations should be interpreted in conjunction with other clinical variables. The relationship between peritoneal and blood l-lactate concentration for predicting SO or SO-SI was complex when included in a multivariable model. Models to predict SO probably vary based on lesion location.

The effect of pre-dosing with metformin on the insulin response to oral sugar in insulin-dysregulated horses.

BACKGROUND: A single dose of metformin administered 1 h prior to oral glucose challenge was previously shown to reduce insulinaemic responses in horses with experimentally-induced insulin dysregulation (ID). Targeted administration could be useful for controlling post-prandial hyperinsulinaemia in horses with naturally-occurring ID. OBJECTIVES: The objective was to compare the insulinaemic and glycaemic responses to oral sugar testing (OST) performed at different intervals after a single dose of metformin in horses with naturally-occurring ID. We hypothesised that pre-treatment with one dose of metformin would significantly decrease the insulinaemic response to OST. STUDY DESIGN: Randomised cross-over in vivo experiment. METHODS: Eight university-owned adult horses with naturally-occurring ID underwent OST 1, 2 and 6 h following a single oral dose of metformin (30 mg/kg) or 1 h after placebo (240 mL water) with a 7-day washout between treatments over a period of 3 weeks. Plasma insulin, C-peptide and glucose concentrations were measured at 0, 60 and 90 min after 0.45 mL/kg light corn syrup and the effect of treatment (and the interval since dosing) examined using a mixed effects linear regression model. RESULTS: Metformin treatment had no significant effect on plasma glucose, insulin or C-peptide concentrations at any time point compared with placebo (p > 0.05). For OST 1 h post metformin, median (IQR) plasma insulin was 91.3 (62.4-114.9) µIU/mL at 60 min versus 76.2 (59.1-134.5) for placebo (p = 0.8) and 62.7 (31.4-109.7) at 90 min versus 51.8 (29.2-126.3) for placebo (p = 0.9). MAIN LIMITATIONS: Small sample size may limit identification of more subtle decreases in insulin concentration with metformin pre-dosing. The results of this study are relevant only for one pre-treatment dose (30 mg/kg) which limits extrapolation to predictions about the effects of longer-term metformin administration on insulin and glucose dynamics in the horse. CONCLUSIONS AND CLINICAL IMPORTANCE: The results do not support the use of targeted metformin treatment to reduce post-prandial hyperinsulinaemia in horses with naturally-occurring ID.

High Doses of Exogenous Glucagon Stimulate Insulin Secretion and Reduce Insulin Clearance in Healthy Humans.

Glucagon is generally defined as a counterregulatory hormone with a primary role to raise blood glucose concentrations by increasing endogenous glucose production (EGP) in response to hypoglycemia. However, glucagon has long been known to stimulate insulin release, and recent preclinical findings have supported a paracrine action of glucagon directly on islet ß-cells that augments their secretion. In mice, the insulinotropic effect of glucagon is glucose dependent and not present during basal euglycemia. To test the hypothesis that the relative effects of glucagon on hepatic and islet function also vary with blood glucose, a group of healthy subjects received glucagon (100 ng/kg) during fasting glycemia or experimental hyperglycemia (∼150 mg/dL) on 2 separate days. During fasting euglycemia, administration of glucagon caused blood glucose to rise due to increased EGP, with a delayed increase of insulin secretion. When given during experimental hyperglycemia, glucagon caused a rapid, threefold increase in insulin secretion, as well as a more gradual increase in EGP. Under both conditions, insulin clearance was decreased in response to glucagon infusion. The insulinotropic action of glucagon, which is proportional to the degree of blood glucose elevation, suggests distinct physiologic roles in the fasting and prandial states.

Determinants of Meal-Induced Changes in Circulating FFA Epoxides, Diols, and Diol-to-Epoxide Ratios as Indices of Soluble Epoxide Hydrolase Activity.

Soluble epoxide hydrolase (sEH) is an important enzyme for metabolic and cardiovascular health. sEH converts FFA epoxides (EpFAs), many of which are regulators of various cellular processes, to biologically less active diols. In human studies, diol (sEH product) to EpFA (sEH substrate) ratios in plasma or serum have been used as indices of sEH activity. We previously showed these ratios profoundly decreased in rats during acute feeding, possibly reflecting decreases in tissue sEH activities. The present study was designed to test which tissue(s) these measurements in the blood represent and if factors other than sEH activity, such as renal excretion or dietary intake of EpFAs and diols, significantly alter plasma EpFAs, diols, and/or their ratios. The results show that postprandial changes in EpFAs and diols and their ratios in plasma were very similar to those observed in the liver but not in other tissues, suggesting that the liver is largely responsible for these changes in plasma levels. EpFAs and diols were excreted into the urine, but their levels were not significantly altered by feeding, suggesting that renal excretion of EpFAs and diols may not play a major role in postprandial changes in circulating EpFAs, diols, or their ratios. Diet intake had significant impacts on circulating EpFA and diol levels but not on diol-to-EpFA (D-to-E) ratios, suggesting that these ratios, reflecting sEH activities, may not be significantly affected by the availability of sEH substrates (i.e., EpFAs). In conclusion, changes in FFA D-to-E ratios in plasma may reflect those in the liver, which may in turn represent sEH activities in the liver, and they may not be significantly affected by renal excretion or the dietary intake of EpFAs and diols.

Neuromuscular electrical stimulation for obstructive sleep apnoea: comparing adherence to active and sham therapy.

Background: Mild obstructive sleep apnoea (OSA) is a common disorder associated with daytime sleepiness and impaired quality of life. Given that adherence to positive airway pressure (PAP) therapy in OSA is suboptimal, alternative strategies are needed particularly for patients with mild OSA. Daytime neuromuscular electrical stimulation (NMES) of the tongue is a new therapeutic modality for mild OSA. The objective of this study was to determine if patients with mild OSA adhere to daytime NMES. Methods: A randomised, sham-controlled, double-masked controlled trial was conducted in 40 patients with mild OSA who received either high-intensity (active) or low-intensity (sham) NMES for 6 weeks. The primary end-point was adherence to therapy. Exploratory outcomes included the respiratory event index (REI) and the Epworth Sleepiness Scale (ESS) score. Results: More than 90% of participants in each arm were adherent to NMES. Exploratory analyses revealed a 32.7% (95% CI 15.5-49.9%) drop in the REI with active NMES, with no significant change in the REI with sham NMES. Improvements were larger in the supine than non-supine REI. Both the apnoea index and hypopnoea index improved with active NMES. Finally, the ESS score improved with active but not with sham NMES. Conclusions: Daytime NMES was well accepted, with a majority using it for the recommended period. NMES of the tongue use was associated with improvements in OSA severity and daytime sleepiness. Additional research is needed to define its role in the treatment armamentarium across the spectrum of OSA severity and in patients who are intolerant to PAP therapy.

Etiology, clinical presentation, and outcome of temporomandibular joint luxation in cats: 21 cases (2000-2018).

This study was performed to report etiology, clinical presentation, treatment, and outcome of temporomandibular joint (TMJ) luxation in 21 cats (2000-2018). TMJ luxation was diagnosed by either dental radiography or computed tomography (CT). Causes for TMJ luxation included altercation with a dog (38%), hit-by-car (19%), unknown (19%), fall (19%), and ran into inanimate object (5%). The most common complication was development of permanent malocclusion (24%), followed by reduced vertical mandibular range of motion (5%). Reduction of TMJ luxation was successful in 94.7% of the cases. Reduction of the TMJ luxation was significantly associated with time from injury to treatment. No other significant associations were observed between cause of injury, type of TMJ stabilization, and outcome. TMJ luxation in cats carries an excellent prognosis with early joint reduction and supportive care. Concurrent dental trauma and maxillofacial injuries are common, and all patients with head trauma must be stabilized and evaluated with a thorough examination.

Pharmacokinetics and pharmacodynamics of intranasal and intramuscular administration of naloxone in working dogs administered fentanyl.

BACKGROUND: Working dogs exposed to narcotics might require reversal in the field. OBJECTIVE: To explore the pharmacokinetic and pharmacodynamic effects of naloxone administered intramuscularly (IM) or intranasally (IN) to reverse fentanyl sedation in working dogs. ANIMALS: Ten healthy, working dogs aged 1.7 ± 1 year and weighing 26 ± 3 kg. METHODS: In this randomized, controlled cross-over study dogs received either 4 mg of naloxone IN or IM 10 minutes after fentanyl (0.3 mg IV) administration. Sedation was assessed at baseline and 5 minutes after fentanyl administration, then at 5, 10, 15, 20, 25, 30, 60 and 120 minutes after reversal with naloxone. Blood samples for naloxone detection were obtained at 0, 5, 10, 30, 60 and 120 minutes. Pharmacokinetic parameters and sedation scores were compared between IM and IN naloxone groups. RESULTS: There was a significant increase in sedation score from baseline (0.25 [-4 to 1] IM; 0 [-2 to 1] IN) after fentanyl administration (11 [5-12] IM; 9.25 [4-11] IN), followed by a significant reduction at 5 (0.5 [-0.5 to 1.5] IM; 1.25 [-1.5 to 4.5] IN) through 120 minutes (-0.5 [-2 to 1] IM; 0 [-4.5 to 1] IN) after reversal with naloxone. Route of administration had no significant effect on sedation score. Maximum plasma concentration was significantly lower after IN administration (11.7 [2.8-18.8] ng/mL IN, 36.7 [22.1-56.4] ng/mL IM, P < .001) but time to reach maximum plasma concentration was not significantly different from IM administration. CONCLUSION AND CLINICAL IMPORTANCE: Although IM administration resulted in higher naloxone plasma concentrations compared to IN, reversal of sedation was achieved via both routes after administration of therapeutic doses of fentanyl.

In vitro evaluation of the effect of tris-EDTA and 0.0005% chlorhexidine solution on the strength of two absorbable sutures.

OBJECTIVE: To determine the effect of 0.0005% chlorhexidine and tris-EDTA solution on the strength of three commonly used suture types for closure of equine ventral midline celiotomy. STUDY DESIGN: Controlled laboratory study. SAMPLE POPULATION: Knotted loops (n = 10/group, 150 knot constructs total). METHODS: Strands of 2 polyglactin 910, 3 polyglactin 910, and 2 polydioxanone were tied to form knotted loops. All knotted loops were mounted on a tabletop force measurement machine system and loaded at 100 mm/min until the breaking force (N) was determined. The breaking force (N) of knotted loops using dry suture was recorded at study start, then of knotted loops soaked in either 0.0005% chlorhexidine and tris-EDTA for 20 min followed by incubation in equine serum (treatment) or serum alone (control) for 14 and 21 days. Analysis of variance (ANOVA) compared the breaking force between the treatment and control groups at each time point. RESULTS: There was no significant difference in the breaking force of 2 USP polyglactin 910 (p = .35, confidence interval [CI] = -0.21-0.59), 3 USP polyglactin 910 (p = .61, CI = -0.41-0.24), or 2 USP polydioxanone (p = .76, CI = -0.63-0.46) soaked in 0.0005% chlorhexidine and tris-EDTA solution followed by equine serum when compared to each respective suture soaked in equine serum only. CONCLUSION/CLINICAL SIGNIFICANCE: Since 0.0005% chlorhexidine and tris-EDTA solution did not exhibit a significant effect on the breaking force of the absorbable sutures studied, the solution may be used for incisional lavage in the clinical setting.

Characterization of impaired beta and alpha cell function in response to an oral glucose challenge in cystic fibrosis: a cross-sectional study.

Aims: The purpose of the study was to further elucidate the pathophysiology of cystic fibrosis (CF)-related diabetes (CFRD) and potential drivers of hypoglycaemia. Hence, we aimed to describe and compare beta cell function (insulin and proinsulin) and alpha cell function (glucagon) in relation to glucose tolerance in adults with CF and to study whether hypoglycaemia following oral glucose challenge may represent an early sign of islet cell impairment. Methods: Adults with CF (≥18 years) were included in a cross-sectional study using an extended (-10, -1, 10, 20, 30, 45, 60, 90, 120, 150, and 180 min) or a standard (-1, 30, 60, and 120 min) oral glucose tolerance test (OGTT). Participants were classified according to glucose tolerance status and hypoglycaemia was defined as 3-hour glucose <3.9 mmol/L in those with normal glucose tolerance (NGT) and early glucose intolerance (EGI). Results: Among 93 participants, 67 underwent an extended OGTT. In addition to worsening in insulin secretion, the progression to CFRD was associated with signs of beta cell stress, as the fasting proinsulin-to-insulin ratio incrementally increased (p-value for trend=0.013). The maximum proinsulin level (pmol/L) was positively associated with the nadir glucagon, as nadir glucagon increased 6.2% (95% confidence interval: 1.4-11.3%) for each unit increase in proinsulin. Those with hypoglycaemia had higher 60-min glucose, 120-min C-peptide, and 180-min glucagon levels (27.8% [11.3-46.7%], 42.9% [5.9-92.85%], and 80.3% [14.9-182.9%], respectively) and unaltered proinsulin-to-insulin ratio compared to those without hypoglycaemia. Conclusions: The maximum proinsulin concentration was positively associated with nadir glucagon during the OGTT, suggesting that beta cell stress is associated with abnormal alpha cell function in adults with CF. In addition, hypoglycaemia seemed to be explained by a temporal mismatch between glucose and insulin levels rather than by an impaired glucagon response.