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Four adult horses with histories of moderate abdominal pain and inappetence were diagnosed with delayed gastric emptying and gastric impaction attributed to pyloroduodenal obstruction (three cases) or duodenitis (one case). A stapled side-to-side gastrojejunostomy was performed on all horses. Two horses returned to work and survived ≥3 years. One horse was euthanased 6 months post-surgery due to recurrent abdominal pain, and one was found dead 5 months postsurgery after an unattended foaling.

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Encephalomyocarditis virus (EMCV) infection was detected by real-time reverse transcription PCR (qRT-PCR) in four adult alpacas (Vicugna pacos) from two properties on the Far North Coast of New South Wales (NSW) in April and May 2018 and in two adult alpacas from a third property on the Central Coast of NSW in October 2018. Viral RNA was detected in a range of samples, including blood, fresh body organs and mucosal swabs. EMCV was isolated from the blood and body organs of five of these alpacas. These animals displayed a range of clinical signs, including inappetence, colic, recumbency and death. Necropsy findings included multifocal to coalescing areas of myocardial pallor, pulmonary congestion and oedema, hepatic congestion and serosal effusion. Histopathological changes comprised acute, multifocal myocardial degeneration and necrosis, with mild, neutrophilic and lymphocytic inflammation (5/5 hearts) and mild, perivascular neutrophilic meningoencephalitis (1/3 brains). This is the first report of disease due to EMCV in alpacas under farm conditions, and it identifies EMCV infection as a differential diagnosis for acute disease and death in this camelid species. In addition to the samples traditionally preferred for EMCV isolation (fresh heart, brain and spleen), blood samples are also appropriate for EMCV detection by qRT-PCR assay.

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OBJECTIVE: Evaluate the effect of topical 1% cannabidiol on second intention wound healing in distal limb wounds of horses. DESIGN: Experimental. ANIMALS: Six Standardbred horses. METHODS: A total of five 2.5 cm × 2.5 cm full thickness skin wounds were created on the dorsomedial aspect of the metacarpi of 6 horses. Wounds were contaminated with faeces on the day of wound creation. Each wound was then assigned to a treatment group; compounded 1% cannabidiol in unique manuka factor (UMF) 5 manuka honey, UMF 5 manuka honey, UMF 20 manuka honey or saline. Each treatment was applied topically daily for a total of 42 days. Legs were bandaged and bandages were changed, daily, for 13 days postoperatively. Digital photographs of each wound were taken on day 1 then weekly for 6 weeks. Wound size, daily healing rate and total time to healing were recorded and compared statistically. RESULTS: Irrespective of the treatment, wounds did not retract as expected in the first 7 days after wound creation. There was no difference in wound area, daily healing rate, days to complete healing between treatment groups. CONCLUSIONS: This preliminary study failed to demonstrate any difference in wound healing variables between treatment groups in this model of second intention wound healing. This was unexpected due to the established effects of UMF 20 manuka honey on wound healing using the same model. This may be due to systemic effects of cannabidiol and study design. Further research into the use of cannabidiol in equine wounds is warranted.

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BACKGROUND: The validity of pediatric estimated glomerular filtration rate equations (eGFRs) in early stages of CKD including hyperfiltration is unknown. The purpose of this study was to develop an eGFR equation for adolescents with obesity and type 2 diabetes (T2D). METHODS: eGFRs were developed from iohexol-derived GFRs (iGFRs) in 26 overweight/obese (BMI > 85th percentile) youth and 100 with T2D from the iCARE (Improving renal Complications in Adolescents with T2D through REsearch) cohort. Twenty percent of the cohort was withheld as a validation dataset. Linear regression analyses were used to develop the best formula based on body size, sex, creatinine, urea, ± cystatin C. Comparable validity of commonly used eGFR equations was assessed. RESULTS: Mean age 15.4 + 2.4 years, BMI Z-score 2.5 + 1.2, 61% female, and mean iGFR 129.0 + 27.7 ml/min/ 1.73 m2. The best adjusted eGFR formula (ml/min/1.73 m2) was 50.7 × BSA0.816 × (height (cm)/creatinine)0.405 × 0.8994 if sex = female | 1 otherwise. It resulted in 53.8% of eGFRs within 10% of measured iGFR and 96.2% within 30%. Bland-Altman 95% limits of agreement in the external dataset were - 37.6 to 45.5 ml/min/1.73m2 (bias = 3.96), and the correlation was 0.62. This equation performed better than all previously published creatinine-based eGFRs. cystatin C did not significantly improve results; however, some other cystatin C formulas also performed well. CONCLUSIONS: The iCARE equation provides a more accurate creatinine-based eGFR in obese youth with and without T2D. Further studies are warranted to evaluate within-subject variability and applicability to lower GFRs and other populations.

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OBJECTIVE: To quantify the time to clear dexamethasone from plasma and urine of horses following a single nebulisation. DESIGN: Experimental using six Standardbred mares. METHODS: Dexamethasone sodium phosphate (0.04 mg/kg) diluted in 0.9% sodium chloride was administered as an aerosol using a Flexineb E2® nebuliser. Blood samples (0, 2, 4, 6, 8, 10, 12, 24, 32, 48, 72 and 96 h) and urine samples (0, 1, 4, 8, 24, 32, 48, 72 and 96 h) were collected for analysis using liquid chromatography mass spectrometry. RESULTS: Maximum plasma concentrations (tmax ) were reached by the earliest detection point (2 h) after nebulisation (0.6-1.8 ng/mL), but was no longer detectable at 48 h. However, in one horse 0.1 ng/mL was found at 96 h after three consecutive readings of 0 ng/mL. The tmax in urine was reached by the earliest collection point (1 h) after nebulisation (3.2-23.8 ng/mL), but was no longer present in urine at 72 h in five horses, while detectable levels (0.1 ng/mL) were still present at 96 h in one horse. CONCLUSIONS: A single dose of 0.04 mg/kg of DSP administered as an aerosol through a FlexinebE2® mask was no longer detectable in blood at 48 h in six horses tested, but one horse returned a reading of 0.1 ng/mL at 96 h after having no detectable levels. Dexamethasone was not detectable in urine at 72 h in five horses but was detectable at a low concentration (0.1 ng/mL) at 96 h in one horse.

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Current therapeutic strategies for pharyngoesophageal stricture, while effective in the short term, are protracted and costly in the longer term. Conceptually, if a stricture can be dilated with minimal tissue injuries, the rate of fibrosis and the resultant stricture recurrence could be reduced. We evaluated a prototype computer-controlled syringe pump device programmed to distend a commercially available balloon dilator at variable rate, asserting incremental lumen distension pressures tailored to the resistive force encountered within the stricture. We completed 17 graded dilatation procedures among 4 total laryngectomy patients. All patients had a short-term response (1 month), with a mean decrement (improvement) in Sydney Swallow Questionnaire score of 448 (total score range, 0-1700; normal <234). The overall procedural tolerability and safety were encouraging; the only complication was the displacement of the voice prosthesis during 1 dilatation. From a technical viewpoint, the main challenge was to maintain the balloon in position during dilatation.

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AIMS To compare the effect of oxygen supplementation using flow-by or a face mask on the partial pressure of arterial oxygen (PaO2) in sedated dogs. METHODS Twenty healthy dogs weighing >15 kg, of mixed sex and breed, were enrolled in a randomised cross-over study. Each dog was sedated with I/M 0.015 mg/kg medetomidine and 0.5 mg/kg methadone. Twenty minutes later dogs were exposed to two 5-minute treatment periods of oxygen supplementation separated by a 15-minute washout period during which dogs were allowed to breathe room air. During the treatment periods, oxygen was delivered at a flow rate of 3 L/minute either through a face mask (face mask oxygenation), or via a tube held 2 cm from the dog's nares (flow-by oxygenation). The order in which the treatments were administered was randomised. Arterial blood was collected for blood gas analysis and rectal temperature measured at four times: prior to commencing treatments, after each treatment, and at the end of the 15 minutes washout period between treatments. RESULTS The mean PaO2 in arterial samples taken from the dogs after face mask oxygen supplementation was 371.3 (SE 13.74) mmHg which was higher than in samples taken after they received flow-by oxygen supplementation (182.2 (SE 6.741) mmHg; p<0.001). The mean PaO2 in samples taken after receiving either form of oxygen supplementation was higher than in samples taken after the dogs had been breathing room air (82.43 (SE 2.143) mmHg; p<0.001). There was no association between sex, age, weight or breed of dogs and blood gas parameters or rectal temperature (p>0.05). CONCLUSIONS Oxygen supplementation delivered using a face mask was more effective at increasing PaO2 than flow-by oxygen supplementation. Flow-by oxygen supplementation at a distance of 2 cm from the nose may be a suitable alternative when the use of a face mask is not tolerated by the patient.

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OBJECTIVE: To compare the effects of two concentrations of oxygen delivered to the anaesthetic breathing circuit on oxygenation in mechanically ventilated horses anaesthetised with isoflurane and positioned in dorsal or lateral recumbency. METHODS: Selected respiratory parameters and blood lactate were measured and oxygenation indices calculated, before and during general anaesthesia, in 24 laterally or dorsally recumbent horses. Horses were randomly assigned to receive 100% or 60% oxygen during anaesthesia. All horses were anaesthetised using the same protocol and intermittent positive pressure ventilation (IPPV) was commenced immediately following anaesthetic induction and endotracheal intubation. Arterial blood gas analysis was performed and oxygenation indices calculated before premedication, immediately after induction, at 10 and 45 min after the commencement of mechanical ventilation, and in recovery. RESULTS: During anaesthesia, the arterial partial pressure of oxygen was adequate in all horses, regardless of position of recumbency or the concentration of oxygen provided. At 10 and 45 min after commencing IPPV, the arterial partial pressure of oxygen was lower in horses in dorsal recumbency compared with those in lateral recumbency, irrespective of the concentration of oxygen supplied. Based on oxygenation indices, pulmonary function during general anaesthesia in horses placed in dorsal recumbency was more compromised than in horses in lateral recumbency, irrespective of the concentration of oxygen provided. CONCLUSION: During general anaesthesia, using oxygen at a concentration of 60% instead of 100% maintains adequate arterial oxygenation in horses in dorsal or lateral recumbency. However, it will not reduce pulmonary function abnormalities induced by anaesthesia and recumbency.

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OBJECTIVE: To compare the effect of application of manuka honey with unique manuka factor (UMF) 5 or 20 with a generic multifloral honey on equine wound healing variables. METHODS: Two full-thickness skin wounds (2.5 × 2.5 cm) were created on the metatarsus of both hindlimbs of eight Standardbred horses. The wounds on each horse were assigned to 1 of 4 treatments: UMF20 (UMF20) and UMF5 (UMF5) manuka honey; generic multifloral honey (GH); and a saline control. Bandages were changed daily for 12 days, after which treatment was stopped and the bandages were removed. Wound area was measured on day 1, then weekly until day 42. Overall wound healing rate (cm2 /day) and time to complete healing were recorded. RESULTS: There was no difference in wound area for any of the treatments on any measurement day except for day 21, where the mean wound area for wounds treated with UMF20 was smaller than the mean wound area for the UMF5-treated wounds (P = 0.031). There was no difference in mean (± SE) overall healing rate (cm2 /day) among the treatment groups. There were differences in mean (± SE) days to complete healing. Wounds treated with UMF20 healed faster than wounds treated with GH (P = 0.02) and control wounds (P = 0.01). CONCLUSIONS: Treatment of wounds with UMF20 reduced overall wound healing time compared with wounds treated with GH and control wounds. However, using this model the difference in the overall time to complete healing was small.

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AIMS To compare the efficacy of an enteric coated esomeprazole paste with an enteric coated omeprazole paste to increase gastric pH after oral administration in horses. METHODS Nine adult Standardbred horses were randomly assigned to three groups, each containing three horses, for a study comprising three phases of 10 days, with an 18-day washout period between each phase. In each phase, three horses received either 0.5 mg/kg esomeprazole, 1 mg/kg omeprazole or a placebo, as an oral paste, once daily for 10 days (Days 0-9). Over the course of study all horses received all three treatments. Gastric fluid samples were collected using a gastroscope on Days 1, 3, 5, 8 and 10, with food and water withheld for 16 hours prior to collection of samples. The pH of all samples was measured immediately after collection. RESULTS Mean pH (3.38; SD 1.75) of the gastric fluid samples in the horses that received the placebo was lower than in the horses that received esomeprazole (6.28; SD 1.75) or omeprazole (6.13; SD 1.75) (p<0.001). There was no difference in the mean pH between horses receiving esomeprazole and those receiving omeprazole (p=0.56). CONCLUSIONS AND CLINICAL RELEVANCE Under these study conditions, esomeprazole paste was equally as effective as omeprazole paste in increasing gastric pH in horses. Enteric coated esomeprazole, may be a therapeutic alternative to omeprazole for the prevention of gastric ulcers in horses.

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CASE REPORT: A newborn foal was referred for evaluation because it had not passed meconium, despite the administration of four enemas. Abdominal radiographs and ultrasound scans showed generalised gaseous distension of the intestine and there was no observable meconium in the colon. Positive contrast colography showed contrast medium extending to the transverse colon. An exploratory laparotomy confirmed the absence of the left and right dorsal colon and the pelvic and diaphragmatic flexures. An end-to-side anastomosis of the left ventral colon to the midpoint of the small colon was performed. The foal recovered from anaesthesia and surgery uneventfully and immediately began suckling from the mare, with no signs of abdominal pain in the postoperative period. The foal began to pass soft faeces 3 days after surgery and at 6 months after surgery the foal was clinically normal and growing at a similar rate to its cohort. CONCLUSION: Intestinal atresia is a rare condition in foals, but should be considered as a differential diagnosis in foals that fail to pass meconium. Early recognition and surgical intervention can offer an improved chance of short-term survival in cases where there is adequate intestine to anastomose. An end-to-side anastomosis technique can be used where an end-to-end technique is not practical because of the difference in diameter of the proximal and distal intestinal segments.

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Prostate cancer is the most common cancer in men and the metastatic form of the disease is incurable. We show here that the drebrin/EB3 pathway, which co-ordinates dynamic microtubule/actin filament interactions underlying cell shape changes in response to guidance cues, plays a role in prostate cancer cell invasion. Drebrin expression is restricted to basal epithelial cells in benign human prostate but is upregulated in luminal epithelial cells in foci of prostatic malignancy. Drebrin is also upregulated in human prostate cancer cell lines and co-localizes with actin filaments and dynamic microtubules in filopodia of pseudopods of invading cells under a chemotactic gradient of the chemokine CXCL12. Disruption of the drebrin/EB3 pathway using BTP2, a small molecule inhibitor of drebrin binding to actin filaments, reduced the invasion of prostate cancer cell lines in 3D in vitro assays. Furthermore, gain- or loss-of-function of drebrin or EB3 by over-expression or siRNA-mediated knockdown increases or decreases invasion of prostate cancer cell lines in 3D in vitro assays, respectively. Finally, expression of a dominant-negative construct that competes with EB3 binding to drebrin, also inhibited invasion of prostate cancer cell lines in 3D in vitro assays. Our findings show that co-ordination of dynamic microtubules and actin filaments by the drebrin/EB3 pathway drives prostate cancer cell invasion and is therefore implicated in disease progression.

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Metabolic heat produced by Thoroughbred racehorses during racing can rapidly elevate core body temperature (1°C/min). When environmental conditions are hot and humid, the normal physiological cooling mechanisms become ineffective. The heat accumulated may exceed a critical thermal maximum (estimated to be 42°C), which may trigger a complex pathophysiological cascade with potentially lethal consequences. This syndrome has been labelled exertional heat illness (EHI). EHI is described in humans, but has not been well documented in Thoroughbred racehorses. The clinical signs described in racehorses would suggest that the pathophysiological events affecting the central nervous (CNS) and gastrointestinal systems are similar to those described in humans. Clinical signs are progressive and include signs of endotoxaemia and increasing levels of CNS dysfunction. Initially, horses that may be mildly irritable (agitated, randomly kicking out) may progress to unmanageable (disorientation, severe ataxia, falling) and ultimately convulsions, coma and death. Currently, the approach to treatment is largely empirical and involves rapid and effective cooling, administration of drugs to provide sedation, administration of non-steroidal anti-inflammatory drugs to ameliorate the effects of endotoxaemia and glucocorticoids to stabilise cell membranes and reduce the effects of inflammation on the CNS. This review provides an overview of the current knowledge about EHI in Thoroughbred racehorses, suggests a likely pathophysiology of the syndrome in horses based on the current literature on heat illness in humans and horses, and outlines current treatment strategies being used to treat racehorses with clinical signs of EHI.

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OBJECTIVE: To investigate the effect of 66% Manuka honey gel on the concentrations of transforming growth factor (TGF)-ß1 and TGF-ß3, bacterial counts and histomorphology during healing of contaminated equine distal limb wounds. METHODS: In this experimental study of 10 Standardbred horses, five full-thickness skin wounds (2 × 1.5 cm) were created on one metacarpus and six similar wounds were created on the contralateral metacarpus. Wounds were assigned to three groups: non-contaminated control wounds; contaminated control wounds; contaminated wounds treated daily with 1 mL Manuka honey gel topically for 10 days. For the contaminated wounds, faeces were applied for 24 h after wound creation. In five horses wounds were bandaged and in the other five horses wounds were left without a bandage. Biopsies were taken on days 1, 2, 7 and 10 after wounding to evaluate the effects of Manuka honey gel, wound contamination and bandaging on TGF-ß1 and TGF-ß3 concentrations, aerobic and anaerobic bacterial counts, and histomorphology. RESULTS: Manuka honey gel had no significant effect on TGF-ß1 and TGF-ß3 concentrations or wound bacterial counts. Manuka honey gel decreased wound inflammation (days 7, 10), increased angiogenesis (days 2, 7, 10), increased fibrosis and collagen organisation (day 7) and increased epithelial hyperplasia (days 7, 10). CONCLUSIONS: Treatment with Manuka honey gel resulted in a more organised granulation tissue bed early in wound repair, which may contribute to enhanced healing of equine distal limb wounds.

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Psychological disturbances, including anxiety and depression, are common during human pregnancy. Our objective was to determine whether these maternal disturbances influence cardiovascular responses of the offspring. The psychological status of 231 pregnant women was determined. Offspring (216) of these women were subsequently exposed to a video challenge stress when aged 7-9 years. Heart rate (HR) and blood pressure (BP) of the children were determined at rest, in response to video stress and during subsequent recovery. Children's resting and stress-induced increases in HR (bpm), systolic (SBP, mm Hg) and diastolic (DBP, mm Hg) BP were all greater in children whose mothers reported anxiety during pregnancy. Values (mean±s.d.) for resting HR, SBP and DBP were 75.15±5.87, 95.37±2.72 and 66.39±4.74 for children whose mothers reported no anxiety and an average of 81.62±6.71, 97.26±2.90 and 68.86±2.82 for children whose mothers reported anxiety at any level. Respective values for stress-induced increments in HR, SBP and DBP were 14.83.±2.14, 16.41±1.97 and 12.72±2.69 for children whose mothers reported no anxiety and 17.95±3.46, 18.74±2.46 and 14.86±2.02 for children whose mothers reported any level of anxiety. Effects of maternal depression were less consistent. The effects of maternal anxiety remained in multivariate analyses, which also included children's birth weight. The results indicate a long-term influence of maternal psychological status during pregnancy on the cardiovascular responses to stress among offspring. These effects may contribute to prenatal influences on subsequent health of the offspring.

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BACKGROUND: Over the past 30 years, the prevalence of diabetes has steadily increased among Canadians, and is particularly evident among First Nations (FN) women. The interplay between FN ancestry, gestational diabetes and the development of subsequent diabetes among mothers remains unclear. METHODS: After excluding known pre-existing diabetes, we explored whether FN ancestry may modify the association between gestational diabetes and post-partum diabetes among women in Manitoba (1981-2011) via a historical prospective cohort database study. We analysed administrative data in the Population Health Research Data Repository using Kaplan-Meier survival analysis and Cox proportional hazards regression. RESULTS: Gestational diabetes was diagnosed in 11 906 of 404 736 deliveries (2.9%), 6.7% of FN and 2.2% of non-FN pregnant women (P < 0.0001). Post-partum diabetes during ≤ 30 years follow-up was more than three times higher among FN women than among non-FN women (P < 0.0001). Diabetes developed in 76.0% of FN and 56.2% of non-FN women with gestational diabetes within the follow-up period. The hazard ratio of gestational diabetes for post-partum diabetes was 10.6 among non-FN women and 5.4 among FN women. Other factors associated with a higher risk of diabetes included lower family income among FN and non-FN women and rural/remote residences among FN women. Among non-FN women, urban residence was associated with a higher risk of diabetes. CONCLUSION: Gestational diabetes increases post-partum diabetes in FN and non-FN women. FN women had substantially more gestational diabetes or post-partum diabetes than non-FN women, partially due to socio-economic and environmental barriers. Reductions in gestational diabetes and socio-economic inequalities are required to prevent diabetes in women, particularly in FN population.

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OBJECTIVE: To investigate the effect of activated protein C (APC) on second intention healing of distal limb wounds in horses. METHODS: In this experimental study of eight Standardbred geldings, six full-thickness skin wounds (2 × 1.5 cm) were created on one metacarpus (biopsy limb) and five similar wounds were created on the contralateral metacarpus (photographed limb). Three wounds on the biopsy limb were treated topically with 190 µg APC on days 1, 3, 6 and 9, while the remaining three wounds were untreated (control). One treated and one control wound were biopsied on days 4, 7 and 11 for histopathology. Wounds on the photographed limb were treated with either 66% Manuka honey gel, a commercial antibiotic ointment (bacitracin-neomycin-polymixin B ointment; BNP) or petrolatum daily throughout healing, treated on days 1,3,6 and 9 with 190 µg APC or left untreated. These wounds were digitally photographed and the wound area measured on day 1, then weekly until day 49. Overall time to healing was recorded. RESULTS: There was no effect of APC on wound size, the rate of healing or the overall time to heal. However, compared with control wounds, histological scoring demonstrated enhanced epithelialisation (day 4) and angiogenesis (day 11). Wound healing variables for wounds treated with APC, Manuka honey gel and control wounds were not different and the variables for wounds treated with BNP and petrolatum demonstrated delayed healing. CONCLUSION: The improvements in histological scores in APC-treated wounds suggest further study into the effect of APC on second intention wound healing in horses is warranted.

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BACKGROUND AND AIMS: To investigate the association between vitamin D levels, angiographic severity of coronary artery disease, arterial stiffness and degree of peripheral arterial disease (PAD) as assessed by ankle brachial index (ABI). METHODS AND RESULTS: 375 patients undergoing coronary angiography from November 2012 to September 2013 were recruited. Serum 25-hydroxyvitamin D (25OHD) levels were measured as were ABI and pulse wave velocity (PWV). Based on the findings of the coronary angiogram, patients were divided into subgroups: Absent, Single, Double and Triple Vessel Disease (as defined by >50% stenosis in each major coronary artery) 0.275 patients not taking vitamin D supplements were included in the analysis. Mean age was 66.0 ± 11.2 (mean ± SD) years. Levels of 25(OH)D were significantly lower in patients with CAD when compared to patients without CAD (57.0 ± 1.73 versus 70.1 ± 2.46 nmol/L; p < 0.01). One way ANOVA revealed triple vessel disease patients had significantly lower 25(OH)D levels when compared to single vessel disease patients (50.6 ± 2.84 nmol/L versus 61.3 ± 3.16 p < 0.01) and trended to be lower when compared to double vessel disease patients (50.6 ± 2.84 versus 59.0 ± 2.99 nmol/L; p = 0.07). Stepwise regression revealed that age, gender (male), hypertension, hyperlipidemia and 25(OH)D were significant predictors of CAD (p < 0.05). Vitamin D was the most significant predictor for CAD (p < 0.001) There was no correlation between 25(OH)D levels, ABI and PWV. CONCLUSION: Among patients presenting for coronary angiography, low serum 25-hydroxyvitamin D levels are associated with the presence and extent of angiographic CAD but not arterial stiffness or PAD.

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