Biological sex does not independently influence time-dependent changes in core temperature and sweating of children exercising in uncompensable heat stress.

PURPOSE: To investigate the influence of biological sex, independent of differences in aerobic fitness and body fatness, on the change in gastro-intestinal temperature (∆Tgi) and whole-body sweat rate (WBSR) of children exercising under uncompensable heat stress. METHODS: Seventeen boys (mean±SD; 13.7±1.3 years) and 18 girls (13.7±1.4) years) walked for 45 min at a fixed rate of metabolic heat production per kg body mass (8 W·kg-1) in 40°C and 30% relative humidity. Sex and V̇O2peak were entered into a Bayesian hierarchical general additive model (HGAM) for Tgi. Sex, V̇O2peak and the evaporative requirement for heat balance (Ereq) were entered into a Bayesian hierarchical linear regression for WBSR. For 26 (12 M, 14 F) of the 35 children with measured body composition, body fat percentage was entered in a separate HGAM and hierarchical linear regression for Tgi and WBSR respectively. RESULTS: Conditional on sex-specific mean V̇O2peak, ∆Tgi was 1.00°C [90% credible intervals: 0.84, 1.16] for boys and 1.17°C [1.01, 1.33] for girls, with a difference of 0.17°C [-0.39, 0.06]. When sex differences in V̇O2peak were accounted for, the difference in ∆Tgi between boys and girls was 0.01°C [-0.25, 0.22]. The difference in WBSR between boys and girls was 0.03 L·h-1 [-0.02, 0.07], when isolated from differences in Ereq. The difference in ∆Tgi between boys and girls was -0.10°C [-0.38, 0.17] when sex differences in body fat (%) were accounted for. CONCLUSION: Biological sex did not independently influence the ∆Tgi and WBSR of children exercising under uncompensable heat stress.

Uncontrolled pain: a call for better study design.

Studies assessing animal pain in veterinary research are often performed primarily for the benefit of animals. Frequently, the goal of these studies is to determine whether the analgesic effect of a novel treatment is clinically meaningful, and therefore has the capacity to improve the welfare of treated animals. To determine the treatment effect of a potential analgesic, control groups are necessary to allow comparison. There are negative control groups (where pain is unattenuated) and positive control groups (where pain is attenuated). Arising out of animal welfare concerns, there is growing reluctance to use negative control groups in pain studies. But for studies where pain is experimentally induced, the absence of a negative control group removes the opportunity to demonstrate that the study methods could differentiate a positive control intervention from doing nothing at all. For studies that are controlled by a single comparison group, the capacity to distinguish treatment effects from experimental noise is more difficult; especially considering that pain studies often involve small sample sizes, small and variable treatment effects, systematic error and use pain assessment measures that are unreliable. Due to these limitations, and with a focus on farm animals, we argue that many pain studies would be enhanced by the simultaneous inclusion of positive and negative control groups. This would help provide study-specific definitions of pain and pain attenuation, thereby permitting more reliable estimates of treatment effects. Adoption of our suggested refinements could improve animal welfare outcomes for millions of animals globally.

Minimal clinically important change of knee flexion in people with knee osteoarthritis after non-surgical interventions using a meta-analytical approach.

BACKGROUND: Minimal clinically important change (MCIC) represents the minimum patient-perceived improvement in an outcome after treatment, in an individual or within a group over time. This study aimed to determine MCIC of knee flexion in people with knee OA after non-surgical interventions using a meta-analytical approach. METHODS: Four databases (MEDLINE, Cochrane, Web of Science and CINAHL) were searched for studies of randomised clinical trials of non-surgical interventions with intervention duration of ≤ 3 months that reported change in (Δ) (mean change between baseline and immediately after the intervention) knee flexion with Δ pain or Δ function measured using tools that have established MCIC values. The risk of bias in the included studies was assessed using version 2 of the Cochrane risk-of-bias tool for randomised trials (RoB 2). Bayesian meta-analytic models were used to determine relationships between Δ flexion with Δ pain and Δ function after non-surgical interventions and MCIC of knee flexion. RESULTS: Seventy-two studies (k = 72, n = 5174) were eligible. Meta-analyses included 140 intervention arms (k = 61, n = 4516) that reported Δ flexion with Δ pain using the visual analog scale (pain-VAS) and Δ function using the Western Ontario and McMaster Universities Osteoarthritis Index function subscale (function-WOMAC). Linear relationships between Δ pain at rest-VAS (0-100 mm) with Δ flexion were - 0.29 (- 0.44; - 0.15) (ß: posterior median (CrI: credible interval)). Relationships between Δ pain during activity VAS and Δ flexion were - 0.29 (- 0.41, - 0.18), and Δ pain-general VAS and Δ flexion were - 0.33 (- 0.42, - 0.23). The relationship between Δ function-WOMAC (out of 100) and Δ flexion was - 0.15 (- 0.25, - 0.07). Increased Δ flexion was associated with decreased Δ pain-VAS and increased Δ function-WOMAC. The point estimates for MCIC of knee flexion ranged from 3.8 to 6.4°. CONCLUSIONS: The estimated knee flexion MCIC values from this study are the first to be reported using a novel meta-analytical method. The novel meta-analytical method may be useful to estimate MCIC for other measures where anchor questions are problematic. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022323927.

Bayesian estimation in veterinary pharmacology: A conceptual and practical introduction.

Sophisticated mathematical and computational tools have become widespread and important in veterinary pharmacology. Although the theoretical basis and practical applications of these have been widely explored in the literature, statistical inference in the context of these models has received less attention. Optimization methods, often with frequentist statistical inference, have been predominant. In contrast, Bayesian statistics have not been widely applied, but offer both practical utility and arguably greater interpretability. Veterinary pharmacology applications are generally well supported by relevant prior information, from either existing substantive knowledge, or an understanding of study and model design. This facilitates practical implementation of Bayesian analyses that can take advantage of this knowledge. This essay will explore the specification of Bayesian models relevant to veterinary pharmacology, including demonstration of prior selection, and illustrate the capability of these models to generate practically useful statistics, including uncertainty statements, that are difficult or impossible to obtain otherwise. Case studies using simulated data will describe applications in clinical trials, pharmacodynamics, and pharmacokinetics, all including multilevel modeling. This content may serve as a suitable starting point for researchers in veterinary pharmacology and related disciplines considering Bayesian estimation for their applied work.

The long and the short of it: Salivary telomere length as a candidate biomarker for hypertension and age-related changes in blood pressure.

Hypertension becomes more prevalent with increasing age. Telomere length (TL) has been proposed as a candidate biomarker and can be accessibly extracted from saliva. However, clarity is needed to evaluate the suitability of using TL as a predictor in such instances. This study investigated salivary TL in a cohort of older adults from the 2008 Health and Retirement Study (n = 3329; F: 58%, mean age: 69.4, SD: 10.3 years) to examine any associations with blood pressure (BP). A Bayesian robust regression model was fit using weakly informative priors to predict the effects of TL with age, sex, systolic BP (SBP), diastolic BP (DBP), and treatment status. There were small effects of treatment (ß: -0.07, 95% CrI [-0.33, 0.19], pd: 71.91%) and sex (ß: -0.10, 95% CrI [-0.27, 0.07], pd: >86.78%). Population effects showed a reduction of 0.01 log2 units in TL with each year of advancing age (95% CrI [-0.01, -0.00]). Conditional posterior predictions suggest that females, and treated individuals, experience greater change in TL with increasing age. Bayes R2 was ~2%. TL declines with increasing age, differs between sexes, and appears to be influenced by antihypertensive drugs. Overall, all effects were weak. The data do not currently support the suitability of salivary TL as a biomarker to predict or understand any age-related changes in BP.

Influence of Biological Sex and Fitness on Core Temperature Change and Sweating in Children Exercising in Warm Conditions.

PURPOSE: This study aimed to investigate the associations of biological sex and aerobic fitness (i.e., V̇O 2peak ) on the change in gastrointestinal temperature (∆ Tgi ) and whole-body sweat rate (WBSR) of children exercising in warm conditions. METHODS: Thirty-eight children (17 boys, mean ± SD = 13.7 ± 1.2 yr; 21 girls, 13.6 ± 1.8 yr) walked for 45 min at a fixed rate of metabolic heat production (8 W·kg -1 ) in 30°C and 40% relative humidity. Biological sex and relative V̇O 2peak were entered as predictors into a Bayesian hierarchical generalized additive model for Tgi . For a subsample of 13 girls with measured body composition, body fat percent was entered into a separate hierarchical generalized additive model for Tgi . Sex, V̇O 2peak , and the evaporative requirement for heat balance ( Ereq ) were entered into a Bayesian hierarchical linear regression for WBSR. RESULTS: The mean ∆ Tgi for boys was 0.71°C (90% credible interval = 0.60-0.82) and for girls 0.78°C (0.68-0.88). A predicted 20 mL·kg -1 ·min -1 higher V̇O 2peak resulted in a 0.19°C (-0.03 to 0.43) and 0.24°C (0.07-0.40) lower ∆ Tgi in boys and girls, respectively. A predicted ~13% lower body fat in the subsample of girls resulted in a 0.15°C (-0.12 to 0.45) lower ∆ Tgi . When Ereq was standardized to the grand mean, the difference in WBSR between boys and girls was -0.00 L·h -1 (-0.06 to 0.06), and a 20-mL·kg -1 ·min -1 higher predicted V̇O 2peak resulted in a mean difference in WBSR of -0.07 L·h -1 (-0.15 to 0.00). CONCLUSIONS: Biological sex did not independently influence ∆ Tgi and WBSR in children. However, a higher predicted V̇O 2peak resulted in a lower ∆ Tgi of children, which was not associated with a greater WBSR, but may be related to differences in body fat percent between high and low fitness individuals.

Biomarkers of endothelial activation and inflammation in dogs with organ dysfunction secondary to sepsis.

Introduction: Alteration in endothelial function during sepsis is thought to play a key role in the progression of organ failure. We herein compared plasma concentrations of endothelial activation biomarkers vascular endothelial growth factor (VEGF), hyaluronan (HA), plasminogen activator inhibitor-1 (PAI-1) and von Willebrand factor (vWF), as well as inflammatory mediator concentrations (IL-6, IL-8, IL-10, C-reactive protein and monocyte chemoattractant protein-1) in dogs with sepsis to healthy dogs. Methods: This study was a multicenter observational clinical trial conducted at two university teaching hospitals from February 2016 until July 2017. The study included 18 client-owned dogs hospitalized with sepsis and at least one distant organ dysfunction, as well as 20 healthy dogs. Plasma biomarker concentrations were measured using ELISA. Severity of illness in dogs with sepsis was calculated using the 5-variable acute physiologic and laboratory evaluation (APPLEFAST) score. Biomarker concentrations were compared between septic and healthy dogs using linear models. Results: Septic peritonitis was the most frequent source of sepsis (11/18; 61%), followed by pneumonia (4/18; 22%). Ten dogs (56%) had only 1 organ dysfunction, whereas 3 dogs (17%) had 2, 3 (17%) had 3, 1 (6%) had 4 and 1 (6%) had 5 organ dysfunctions. The median APPLEFAST score in the septic dogs was 28.5 (Q1-Q3, 24-31). Mean plasma concentrations of all endothelial and inflammatory biomarkers, except vWF, were higher in the sepsis cohort than in controls. The mean endothelial biomarker concentrations in the septic cohort ranged from ~2.7-fold higher for HA (difference in means; 118.2 ng/mL, 95% credible limit; 44.5-221.7) to ~150-fold for VEGF (difference in means; 76.6 pg./mL, 95% credible limit; 33.0-143.4), compared to the healthy cohort. Fifteen dogs with sepsis (83%) died; 7 (46%) were euthanized and 8 (53%) died during hospitalization. Conclusion: Dogs with naturally occurring sepsis and organ dysfunction had higher mean concentrations of biomarkers of endothelial activation and inflammation compared to healthy dogs, broadening our understanding of the pathophysiology of sepsis secondary to endothelial dysfunction.

Evidence for key individual characteristics associated with outcomes following combined first-line interventions for knee osteoarthritis: A systematic review.

OBJECTIVE: To identify individual characteristics associated with outcomes following combined first-line interventions for knee osteoarthritis. METHODS: MEDLINE, CINAHL, Scopus, Web of Science Core Collection and the Cochrane library were searched. Studies were included if they reported an association between baseline factors and change in pain or function following combined exercise therapy, osteoarthritis education, or weight management interventions for knee osteoarthritis. Risk of bias was assessed using Quality in Prognostic Factor Studies. Data was visualised and a narrative synthesis was conducted for key factors (age, sex, BMI, comorbidity, depression, and imaging severity). RESULTS: 32 studies were included. Being female compared to male was associated with 2-3 times the odds of a positive response. Older age was associated with reduced odds of a positive response. The effect size (less than 10% reduction) is unlikely to be clinically relevant. It was difficult to conclude whether BMI, comorbidity, depression and imaging severity were associated with pain and function outcomes following a combined first-line intervention for knee osteoarthritis. Low to very low certainty evidence was found for sex, BMI, depression, comorbidity and imaging severity and moderate certainty evidence for age. Varying study methods contributed to some difficulty in drawing clear conclusions. CONCLUSIONS: This systematic review found no clear evidence to suggest factors such as age, sex, BMI, OA severity and presence of depression or comorbidities are associated with the response to first-line interventions for knee OA. Current evidence indicates that some groups of people may respond equally to first-line interventions, such as those with or without comorbidities. First-line interventions consisting of exercise therapy, education, and weight loss for people with knee OA should be recommended irrespective of sex, age, obesity, comorbidity, depression and imaging findings.

Tracheal cellular immune response in chickens inoculated with Mycoplasma synoviae vaccine, MS-H or its parent strain 86079/7NS.

Mycoplasma synoviae causes respiratory tract disease in chickens characterised by mild to moderate lymphoplasmacytic infiltration of the tracheal mucosa. MS-H (Vaxsafe1 MS, Bioproperties Pty Ltd.) is an effective live attenuated vaccine for M. synoviae, but the immunological basis for its mechanism of protection has not been investigated, and the phenotypes of lymphocytes and associated cytokines involved in the local adaptive immune response have not been described previously. In this study, specific-pathogen-free chickens were inoculated intra-ocularly at 3 weeks of age with either M. synoviae vaccine strain MS-H or vaccine parent strain 86079/7NS (7NS), or remained uninoculated. At 2-, 7- and 21 days post-inoculation (dpi), tracheal mucosal pathology, infiltrating lymphocytes subsets and transcription levels of mRNA encoding 8 cytokines were assessed using light microscopy, indirect immunofluorescent staining and RT-qPCR, respectively. After inoculation, tracheal mucosal thickness, tracheal mucosal lesions, and numbers of infiltrating CD4+CD25- cells, B-cells, and macrophages were greater in MS-H- and 7NS-inoculated chickens compared with non-inoculated. Inoculation with 7NS induced up-regulation of IFN-γ, while vaccination with MS-H induced up-regulation of IL-17A, when compared with non-inoculated birds. Both inoculated groups had a moderate infiltrate of CD4+CD25+ T cells in the tracheal mucosa. These findings reveal that the tracheal local cellular response after MS-H inoculation is dominated by a Th-17 response, while that of 7NS-inoculated chickens is dominated by a Th-1 type response.

The Surface Area to Volume Ratio Changes the Pharmacokinetic and Pharmacodynamic Parameters in the Subcutaneous Tissue Cage Model: As Illustrated by Carprofen in Sheep.

Introduction: Pharmacokinetic and pharmacodynamic models can be powerful tools for predicting outcomes. Many models are based on repetitive sampling of the vascular space, due to the simplicity of obtaining samples. As many drugs do not exert their effect in the vasculature, models have been developed to sample tissues outside the bloodstream. Tissue cages are hollow devices implanted subcutaneously, or elsewhere, that are filled with fluid allowing repetitive sampling to occur. The physical dimensions of the cage, namely, the diffusible surface area to volume ratio, would be expected to change the rate of drug movement into and out of tissue cages. Methods: Seven sheep were implanted with five pairs of tissue cages, subcutaneously. Each pair of cages had a different length but a fixed diffusible surface area, so the surface area to volume ratio differed. Carrageenan was injected into half of the cages in each animal during one sampling period in a cross-over design. Samples from each cage and the bloodstream were obtained at 14-time points during two sampling periods. The concentration of carprofen was measured using LC-MS/MS and the results were modeled using nonlinear mixed-effects techniques. Prostaglandin metabolites were also measured and the change over time was analyzed using linear mixed effect modeling. Results: The presence of carrageenan within an animal changed the systemic pharmacokinetics of carprofen. The rate of drug movement into and out of the tissue cages varied with the surface area to volume ratio. The concentration time curve for prostaglandin metabolites changed with cage size. Conclusion: The surface area volume ratio of tissue cages will influence the calculated pharmacokinetic parameters and may affect calculated pharmacodynamics, thus, it is an important factor to consider when using tissue cage data for dosing regimes.

Biomechanical Comparison of a 3-Loop Pulley and a 4-Loop Pulley Suture for Tenorrhaphy in the Canine Gastrocnemius Tendon.

OBJECTIVE: The aim of this study was to compare a 3-loop pulley (3LP) suture pattern with a 4-loop pulley (4LP) suture pattern for the tenorrhaphy of the canine gastrocnemius tendon STUDY DESIGN: Randomized, cadaveric, biomechanical study of 30 canine gastrocnemius tendons. Tendons were transected and repaired with either 3LP or 4LP suture pattern with 2-0 polypropylene. A tensile load was applied at 25 mm/min until construct failure. The load required to form a 1 mm gap, 3 mm gap and maximum load at failure was recorded and compared between groups. RESULTS: The estimated mean load to form a 1 mm gap for the 3LP and 4LP was 28.4 N (95% confidence interval [CI]: 24.0-32.6N) and 45.5 N (95% CI: 40.7-50.1N) respectively. The 4LP mean load to form a 1 mm gap was 17.1 N (95% CI: 11.7-22.5N) greater than the 3LP. The estimated mean load to form a 3mm gap for the 3LP and 4LP was 39.7 N (95% CI: 34.1-45.4N) and 55.0 N (95% CI: 49.3-60.9N) respectively. The mean load to form a 3mm gap was 15.3 N (95% CI: 8.5-21.9N) greater in the 4LP than the 3LP. The estimated mean load for failure in the 3LP and 4LP was 41.2 N (95% CI: 35.6-46.9 N) and 54.3 N (95% CI: 48.7-60.3 N) respectively. CONCLUSION: A 4LP pattern was biomechanically superior to a 3LP pattern, as demonstrated by a greater load required to form both a 1 and 3 mm gap and a greater load for failure CLINICAL SIGNIFICANCE: A 4LP suture pattern better resists gap formation and requires greater load prior to construct failure compared with a 3LP, in this canine gastrocnemius model.

Response of canine thyroid carcinomas to radioiodine.

Radioactive iodine (131 I) has previously been reported to prolong survival in dogs with thyroid carcinoma. This study aimed to describe tumour response and progression-free interval (PFI) in dogs with thyroid carcinomas treated with 131 I. Secondary aims were to describe overall survival time (OST) and prognostic factors. A bi-institutional retrospective review of records identified 66 dogs with thyroid carcinoma treated with 131 I from January 2010 to April 2020. Response was described using RECIST or a subjective response assessment where specific tumour measurements were not available. Forty-eight dogs (72.7%) were treatment naïve and 18 dogs (27.3%) had received prior therapy at the time of 131 I treatment. Objective responses were available for 34 dogs and subjective responses for 58 dogs. The overall response rate was 35.3% (four complete and eight partial responses). Improvement of clinical signs was seen in 76.2% of dogs (32/42). Kaplan-Meier-estimated median PFI (95% confidence interval [CI]) was 301 (217-578) days and OST (95% CI) was 564 (421-865) days. Prior therapy was associated with a lower hazard for progression (hazard ratio [HR] 0.260 95% CI 0.123-0.548, p = .0004). Treatment of thyroid carcinoma using 131 I can effectively alleviate clinical signs and reduce disease burden in a proportion of dogs.

Can calf age be estimated using a combination of serum gamma-glutamyl transferase, total protein and immunoglobulin G?

Our aim was to test a novel method for estimating the age of young calves, using serum γ-glutamyl transferase (GGT) activity, total protein concentration and immunoglobulin G (IgG) concentration. Blood samples were taken from 59 dairy calves at 2, 4, 6, 8, 10, 12, and 14 days of age, and serum GGT activity, total protein concentration, and IgG concentration were measured. Bayesian regression models were used to estimate the association of GGT, total protein, and IgG, with calf age. A multivariate hierarchical regression model was then created, and the model's reliability in estimating the age of simulated subjects was assessed. The univariate models showed a strong within-calf relationship between age and GGT (conditional R2 (cR2) = 0.93), and age and total protein (cR2 = 0.75), while the relationship between calf age and IgG was less consistent (cR2 = 0.63). There was a high degree of variation between calves for these parameters, particularly for the relationship between age and total protein (marginal R2 (mR2) 0.02), and age and IgG (mR2 0.01); somewhat less between-calf variation was seen for GGT (mR2 0.30). For the final multivariate model, we tested the model reliability by simulating new subjects. The credible intervals for estimates of calf age generated from the model were wide, indicating poor reliability. We concluded that single measurements of serum GGT activity, total protein concentrations and IgG concentrations cannot be used to reliably estimate the age of young calves to within 1-2 days.

Hierarchical modelling of immunoglobulin coated bacteria in dogs with chronic enteropathy shows reduction in coating with disease remission but marked inter-individual and treatment-response variability.

Chronic enteropathies are a common problem in dogs, but many aspects of the pathogenesis remain unknown, making the therapeutic approach challenging in some cases. Environmental factors are intimately related to the development and perpetuation of gastrointestinal disease and the gut microbiome has been identified as a contributing factor. Previous studies have identified dysbiosis and reduced bacterial diversity in the gastrointestinal microbiota of dogs with chronic enteropathies. In this case-controlled study, we use flow cytometry and 16S rRNA sequencing to characterise bacteria highly coated with IgA or IgG in faecal samples from dogs with chronic enteropathy and evaluated their correlation with disease and resolution of the clinical signs. IgA and IgG-coated faecal bacterial counts were significantly higher during active disease compared to healthy dogs and decreased with the resolution of the clinical signs. Characterisation of taxa-specific coating of the intestinal microbiota with IgA and IgG showed marked variation between dogs and disease states, and different patterns of immunoglobulin enrichment were observed in dogs with chronic enteropathy, particularly for Erysipelotrichaceae, Clostridicaceae, Enterobacteriaceae, Prevotellaceae and Bacteroidaceae, families. Although, members of these bacterial groups have been associated with strong immunogenic properties and could potentially constitute important biomarkers of disease, their significance and role need to be further investigated.

Longitudinal Survey of Fecal Microbiota in Healthy Dogs Administered a Commercial Probiotic.

The aim of this longitudinal microbiome study was to investigate the effects of a commercially available veterinary synbiotic product (Blackmore's® Paw DigestiCare 60™) on the fecal microbiome of healthy dogs using 16S rRNA gene microbial profiling. Fifteen healthy, privately-owned dogs participated in a 2-week trial administration of the product. Fecal samples were collected at different time points, including baseline (prior to treatment), during administration and after discontinuation of product. Large intra- and inter-individual variation was observed throughout the study, but microbiome composition at higher phylogenetic levels, alpha and beta diversity were not significantly altered after 2 weeks of probiotic administration, suggesting an absence of probiotic impact on microbial diversity. Administration of the synbiotic preparation did, however, result in transient increases in probiotic species from Enterococacceae and Streptococacceae families as well as an increase in Fusobacteria; with the fecal microbiota partially reverting to its baseline state 3-weeks after cessation of probiotic administration.

Effect of sequentially fed high protein, hydrolyzed protein, and high fiber diets on the fecal microbiota of healthy dogs: a cross-over study.

BACKGROUND: Dietary content and environmental factors can shape the gut microbiota, and consequently, the way the gut microbiota metabolizes fats, carbohydrates, and proteins, affecting overall health of the host. We evaluated the impact of 3 diets (all meat [raw], high-insoluble fiber dry extruded diet and hydrolyzed protein dry extruded diet) on the gut microbiota of healthy dogs in a cross-over sequential study. RESULTS: We showed that diet can have an effect on the gut microbiome in dogs, which was influenced by the order of feeding. High-protein (all meat) diets were characterized by an increase in bacteria belonging to the Fusobacteria and Bacteroidetes phyla, whereas a high-insoluble fiber commercial diet correlated with increases in Firmicutes and Actinobacteria phyla. However, the individual dog's baseline microbiota had the most impact on the magnitude and nature of the changes in response to dietary intervention. CONCLUSION: Our results suggest that the dog fecal microbiota is driven by protein and fiber composition to different degrees in individual animals, and targeted modification of these patterns could be useful in the modulation of the gut microbiota in different diseases.

A Survey of Injuries That Occurred in Veterinary Teaching Hospitals during 2017.

Knowing the frequency, extent or severity of injuries that occur to students and staff within veterinary teaching hospitals (VTHs) is necessary for proactive management of their safety. This study surveyed contemporaneously-captured incident reports likely to cause or causing injury to students and staff of veterinary teaching hospitals in Europe, the United States of America (USA), Canada, Australia, and New Zealand, recorded in 2017. Four different severities of incident were evaluated within four different cohorts of people, precipitated by five categories for cause. Within each cause-category, further subdivision was based on the nature of the incident. All colleges of veterinary medicine accredited by the American Veterinary Medical Association (AVMA) Council on Education (COE) or the Australasian Veterinary Boards Council were surveyed. Responses were received from (7/7, 100%) schools in Australia and New Zealand, 12/30 (40%) the United States of America, 1/4 (25%) Canada, 1/1 (100%) Mexico, and 1/3 (33%) United Kingdom, and no responses were received from the AVMA-COE accredited schools in the European Union. The mean incidence of incidents caused by horses was (0.4/1,000 cases), followed by food animals (0.1/1,000 cases), other animals (0.1/1,000 cases), and small animals (0.074/1,000 cases). Within veterinary teaching hospitals at many institutions, veterinary students and veterinarians are particularly at risk of injuries caused by hand-held instruments, such as scalpels and needles. Non-veterinary staff are more at risk than students or veterinarians from injuries caused by small animals. Recording and reporting of incidents is not uniform and may be lacking in detail. Some institutions' systems for record management preclude easy evaluation, and therefore may be insufficient for proactive management of health and safety as required by accreditation bodies.

Comparison of the use of a vessel-sealing device versus ligatures for occlusion of uterine tissues during ovariohysterectomy or ovariectomy in rabbits (Oryctolagus cuniculus).

OBJECTIVE: To compare the bursting strength of the uterine horns (UHs) and cervical-vestibule junction (CVJs) of rabbits following sealing with a vessel-sealing device (VSD) or encircling ligatures. SAMPLE: UHs and CVJs collected from 30 rabbit (Oryctolagus cuniculus) cadavers. PROCEDURES: UHs and CVJs were randomly assigned to sealing with encircling Miller knot ligatures (LIG; n = 10 CVJs and 20 UHs) or a VSD (12 CVJs and 24 UHs). Lumens were infused with saline (0.9% NaCl) solution under pressure until seals burst or to a maximum pressure of 300 mm Hg. RESULTS: For CVJs, median (range) bursting pressure of the LIG and VSD groups was > 300 mm Hg (224 to > 300 mm Hg) and 35 mm Hg (0 to 60 mm Hg), respectively. Five of 12 CVJs in the VSD group failed at pressures < 33 mm Hg. For UHs, median (range) bursting pressure of the LIG and VSD groups was 255 mm Hg (120 to > 300 mm Hg) and 154 mm Hg (range, 44 to 202 mm Hg), respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The evaluated VSD was effective in sealing UHs at bursting pressures well in excess of expected physiologic pressures, indicating that the VSD may be useful for ovariectomy procedures in rabbits. However, CVJ seals created with the VSD were ineffective and could potentially burst at low pressures, which could predispose to urine entering the abdomen. Given these results, we do not recommend sealing of the CVJ with a VSD for ovariohysterectomy in rabbits.

Estradiol-17ß Pharmacokinetics and Histological Assessment of the Ovaries and Uterine Horns following Intramuscular Administration of Estradiol Cypionate in Feral Cats.

The control of feral cats (Felis catus) in Australia is a key biological conservation issue. Male cats are more difficult to control than female cats. Collared and tagged female cats displaying estrous behavior have been considered as a way to lure male cats and reveal their locations. As female cats are seasonal breeders, artificial induction of estrous behavior following the administration of a long-acting estrogen could improve their use for this purpose. Estradiol cypionate was intramuscularly administered to nine entire non-pregnant female feral cats, of unknown estrous status, at 0.1, 0.3, or 0.5 mg/kg. Mean peak serum concentrations of estradiol-17ß were 365 pg/mL (0.1 mg/kg), 1281 pg/mL (0.3 mg/kg), and 1447 pg/mL (0.5 mg/kg). The time-course of estradiol-17ß concentrations after various doses of estradiol cypionate was assessed using non-compartmental and non-linear mixed-effects methods. At the highest-studied dose (0.5 mg/kg), the 50th percentile of estradiol-17ß concentrations exceeded 0.1 ng/mL for 11.8 days, and 0.05 ng/mL for 14.6 days. The duration increased with increasing dose. No signs of toxicity were noticed in any cat during the study. This information will be useful to ongoing studies that are investigating ways to reduce the abundance of feral cats in Australia, especially adult male cats.

Physiologically based modelling of the pharmacokinetics of three beta-lactam antibiotics after intra-mammary administration in dairy cows.

Understanding the pharmacokinetics of intra-mammary antibiotics is important for the prediction of drug residues in milk and for the design of optimal dosage regimens. Unfortunately, compartmental pharmacokinetic models are not valid for this unique system. A minimal physiologically based pharmacokinetic model is presented incorporating the physiology of milk secretion, drug administration at the quarter level, drug absorption and dispersion, drug retention during the inter-milking interval and episodic drug elimination at milking. The primary objective of the study was the development and exploration of a model for major factors controlling drug concentration in milk, rather than generation of rigorously predictive pharmaco-statistical models for any particular drug. This model was implemented in a two-stage approach, using published concentration data for penicillin, cefuroxime, cephapirin and desacetyl-cephapirin in milk of healthy cows. Model simulations evaluated sensitivity and developed predictions of drug residues. The model successfully predicted both drug concentrations and drug residues in milk. The postmilking residual milk volume did not adequately explain antibiotic pharmacokinetics, requiring additional considerations for drug retention. Local sensitivity analysis indicated that increasing the number of quarters treated, the dosage, or the duration of the inter-milking interval prolonged both the persistence of drug residues and the duration that antibiotic concentration exceeded typical minimum inhibitory concentrations. The model was flexible across different beta-lactam drugs as a general description of intra-mammary pharmacokinetics. This model is suitable for the design and analysis of dosage regimens, and could be applied for the prediction of withholding periods when these antibiotic preparations are used off-label. The final model indicates that explicit consideration of the milking regimen is fundamental to the design and interpretation of pharmacokinetic studies of antibiotics in bovine milk.