Veterinary Biosciences - Research Publications

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    The role of animal welfare in improving the future of farming
    Doyle, RE ; Campbell, AJD ; Dione, M ; Woodruff, M ; Munoz, C ; Alemayehu, G ; Berhe, T ; Knight-Jones, T ; Wilson, C (CSIRO Publishing, 2022)
    Context: Animal production plays a critical role in many global challenges around sustainability, including climate change and resilience, One Health and food security. With this role comes pressures on livestock welfare. Aims: This paper demonstrates key contributions animal welfare makes to global sustainability challenges. Methods: This paper highlights ‘win–win’ improvements for both animal welfare and other aspects of sustainability by using the following four case studies: tail docking Australian sheep, agroforestry systems in Ethiopia, the Australian dairy-beef industry, and strategic feeding of goats in Pakistan. Key results: These case studies show how animal welfare can be improved alongside livelihoods. However, even in these win–win situations, the adoption of improved practices is not guaranteed. Conclusions: Long-term, sustained change in animal welfare can simultaneously make in roads to other challenges around sustainability. To do this, we must have a broader understanding of the system in which the animals are raised, so that barriers to change can be identified. Implications: Lessons from these case studies can be applied to other production contexts and challenges, highlighting the universal value of understanding and addressing animal welfare.
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    A survey of veterinarians' practices, recommendations and perceptions associated with the prevention of tetanus in horses in Australia
    Dennis, ST ; El Hage, CM ; Brookes, VJ (WILEY, 2022-04)
    OBJECTIVE: Identify veterinarians' practices, recommendations and perceptions when preventing tetanus in horses in Australia. METHODS: Graduated members of Equine Veterinarians Australia participated in an online survey about the prevention of tetanus in horses in Australia. RESULTS: Of 77 respondents (response rate ~ 8%), 50 (65%) reported that they had attended collectively 145-152 cases of tetanus in horses in Australia (1.1 cases of tetanus observed/10 veterinarian-years since qualification). The estimated case fatality rate (CFR) was at least 79%. Puncture wounds were most frequently suspected as the entry point (32%; n = 47). Five respondents (7%) reported cases of localised tetanus. Three respondents reported generalised tetanus within 2 weeks of tetanus antitoxin (TAT) administration. Respondents did not report any cases of tetanus in horses which had been vaccinated according to manufacturer's recommendations. All respondents recommended vaccination, but over 50% (N = 45) stated 'lack of veterinary recommendation' as often or sometimes a reason why clients did not vaccinate horses. Opinions varied on the use of TAT for peri-exposure prophylaxis; 67% of respondents dosed TAT independent of body weight, with the rest dosing according to body weight. Cases of Theiler's disease related to the use of TAT were not reported in Australia by respondents. DISCUSSION: The caseload of equine tetanus appears relatively low among equine veterinarians in Australia. Consistent with the literature, estimated CFR was high. Respondents' recommendations and perceptions about tetanus vaccination were generally consistent but varied regarding TAT usage. Evidence for TAT usage is limited and we recommend studies of TAT efficacy in horses.
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    Protease-activated receptor-2 dependent and independent responses of bone cells to prostate cancer cell secretory products
    Pagel, CN ; Kularathna, PK ; Sanaei, R ; Young, ND ; Hooper, JD ; Mackie, EJ (WILEY, 2022-05)
    BACKGROUND: Metastatic prostate cancer lesions in the skeleton are frequently characterized by excessive formation of bone. Prostate cancer cells secrete factors, including serine proteases, that are capable of influencing the behavior of surrounding cells. Some of these proteases activate protease-activated receptor-2 (PAR2 ), which is expressed by osteoblasts (bone-forming cells) and precursors of osteoclasts (bone-resorbing cells). The aim of the current study was to investigate a possible role for PAR2 in regulating the behavior of bone cells exposed to metastatic prostate cancer cells. METHODS: The effect of medium conditioned by the PC3, DU145, and MDA-PCa-2b prostate cancer cell lines was investigated in assays of bone cell function using cells isolated from wildtype and PAR2 -null mice. Osteoclast differentiation was assessed by counting tartrate-resistant acid phosphatase-positive multinucleate cells in bone marrow cultured in osteoclastogenic medium. Osteoblasts were isolated from calvariae of neonatal mice, and BrdU incorporation was used to assess their proliferation. Assays of alkaline phosphatase activity and quantitative PCR analysis of osteoblastic gene expression were used to assess osteoblast differentiation. Responses of osteoblasts to medium conditioned by MDA-PCa-2b cells were analyzed by RNAseq. RESULTS: Conditioned medium (CM) from all three cell lines inhibited osteoclast differentiation independently of PAR2 . Media from PC3 and DU145 cells had no effect on assays of osteoblast function. Medium conditioned by MDA-PCa-2b cells stimulated BrdU incorporation in both wildtype and PAR2 -null osteoblasts but increased alkaline phosphatase activity and Runx2 and Col1a1 expression in wildtype but not PAR2 -null cells. Functional enrichment analysis of RNAseq data identified enrichment of multiple gene ontology terms associated with lysosomal function in both wildtype and PAR2 -null cells in response to MDA-PCa-2b-CM. Analysis of individual genes identified osteogenesis-associated genes that were either upregulated by MDA-PCa-2b-CM selectively in wildtype cells or downregulated selectively in PAR2 -null cells. CONCLUSIONS: Factors secreted by prostate cancer cells influence bone cell behavior through both PAR2 -dependent and -independent mechanisms. Both PAR2 -independent suppression of osteoclast differentiation and PAR2 -dependent stimulation of osteogenesis are likely to determine the nature of prostate cancer metastases in bone.
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    Overcoming challenges in extracting prescribing habits from veterinary clinics using big data and deep learning
    Hur, B ; Hardefeldt, LY ; Verspoor, K ; Baldwin, T ; Gilkerson, JR (WILEY, 2022-05)
    Understanding antimicrobial usage patterns and encouraging appropriate antimicrobial usage is a critical component of antimicrobial stewardship. Studies using VetCompass Australia and Natural Language Processing (NLP) have demonstrated antimicrobial usage patterns in companion animal practices across Australia. Doing so has highlighted the many obstacles and barriers to the task of converting raw clinical notes into a format that can be readily queried and analysed. We developed NLP systems using rules-based algorithms and machine learning to automate the extraction of data describing the key elements to assess appropriate antimicrobial use. These included the clinical indication, antimicrobial agent selection, dose and duration of therapy. Our methods were applied to over 4.4 million companion animal clinical records across Australia on all consultations with antimicrobial use to help us understand what antibiotics are being given and why on a population level. Of these, approximately only 40% recorded the reason why antimicrobials were prescribed, along with the dose and duration of treatment. NLP and deep learning might be able to overcome the difficulties of harvesting free text data from clinical records, but when the essential data are not recorded in the clinical records, then, this becomes an insurmountable obstacle.
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    Novel Phosphonium-Based Ionic Liquid Electrolytes for Battery Applications.
    Hofmann, A ; Rauber, D ; Wang, T-M ; Hempelmann, R ; Kay, CWM ; Hanemann, T (MDPI AG, 2022-07-24)
    In this study, we address the fundamental question of the physicochemical and electrochemical properties of phosphonium-based ionic liquids containing the counter-ions bis(trifluoromethanesulfonyl)imide ([TFSI]-) and bis(fluorosulfonyl)imide ([FSI]-). To clarify these structure-property as well as structure-activity relationships, trimethyl-based alkyl- and ether-containing phosphonium ILs were systematically synthesized, and their properties, namely density, flow characteristics, alkali metal compatibility, oxidative stability, aluminum corrosivity as well as their use in Li-ion cells were examined comprehensively. The variable moiety on the phosphonium cation exhibited a chain length of four and five, respectively. The properties were discussed as a function of the side chain, counter-ion and salt addition ([Li][TFSI] or [Li][FSI]). High stability coupled with good flow characteristics were found for the phosphonium IL [P1114][TFSI] and the mixture [P1114][TFSI] + [Li][TFSI], respectively.
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    Performance Evaluation and Validation of Air Samplers To Detect Aerosolized Coxiella burnetii
    Abeykoon, AMH ; Poon, M ; Firestone, SM ; Stevenson, MA ; Wiethoelter, AK ; Vincent, GA ; Uzal, F (AMER SOC MICROBIOLOGY, 2022-10-26)
    Coxiella burnetii, the etiological agent of Q fever, is an intracellular zoonotic pathogen transmitted via the respiratory route. Once released from infected animals, C. burnetii can travel long distances through air before infecting another host. As such, the ability to detect the presence of C. burnetii in air is important. In this study, three air samplers, AirPort MD8, BioSampler, and the Coriolis Micro, were assessed against a set of predetermined criteria in the presence of three different aerosolized C. burnetii concentrations. Two liquid collection media, phosphate-buffered saline (PBS) and alkaline polyethylene glycol (Alk PEG), were tested with devices requiring a collection liquid. Samples were tested by quantitative polymerase chain reaction assay (qPCR) targeting the single-copy com1 gene or multicopy insertion element IS1111. All air samplers performed well at detecting airborne C. burnetii across the range of concentrations tested. At high nebulized concentrations, AirPort MD8 showed higher, but variable, recovery probabilities. While the BioSampler and Coriolis Micro recovered C. burnetii at lower concentrations, the replicates were far more repeatable. At low and intermediate nebulized concentrations, results were comparable in the trials between air samplers, although the AirPort MD8 had consistently higher recovery probabilities. In this first study validating air samplers for their ability to detect aerosolized C. burnetii, we found that while all samplers performed well, not all samplers were equal. It is important that these results are further validated under field conditions. These findings will further inform efforts to detect airborne C. burnetii around known point sources of infection. IMPORTANCE Coxiella burnetii causes Q fever in humans and coxiellosis in animals. It is important to know if C. burnetii is present in the air around putative sources as it is transmitted via inhalation. This study assessed air samplers (AirPort MD8, BioSampler, and Coriolis Micro) for their efficacy in detecting C. burnetii. Our results show that all three devices could detect aerosolized bacteria effectively; however, at high concentrations the AirPort performed better than the other two devices, showing higher percent recovery. At intermediate and low concentrations AirPort detected at a level higher than or similar to that of other samplers. Quantification of samples was hindered by the limit of quantitation of the qPCR assay. Compared with the other two devices, the AirPort was easier to handle and clean in the field. Testing air around likely sources (e.g., farms, abattoirs, and livestock saleyards) using validated sampling devices will help better estimate the risk of Q fever to nearby communities.
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    Molecular detection of two new putative species of gammaherpesvirus in petaurid possums
    Douch, JK ; Devlin, JM ; Whiteley, P ; Hartley, CA ; Vaz, PK (WILEY, 2022-11)
    A molecular survey of herpesviruses in Australian native mammals was conducted, spanning 260 individuals from 27 species. Among the herpesviruses detected, a putative new gammaherpesvirus species was detected in the yellow-bellied glider (Petaurus australis), and another in the critically endangered Leadbeater's possum (Gymnobelideus leadbeateri). In addition, the known host range of the putative species macropodid gammaherpesvirus 3 (MaHV-3) is herein extended to the western grey kangaroo (Macropus fuliginosus). These findings expand our understanding of herpesviruses in Australian mammals and may inform biosecurity protocols for captive and translocated populations.
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    Substrate Peptidomimetic Inhibitors of P. falciparum Plasmepsin X with Potent Antimalarial Activity
    Richardson, LW ; Ashton, TD ; Dans, MG ; Nguyen, N ; Favuzza, P ; Triglia, T ; Hodder, AN ; Ngo, A ; Jarman, KE ; Cowman, AF ; Sleebs, BE (WILEY-V C H VERLAG GMBH, 2022-09-16)
    Plasmepsin X (PMX) is an aspartyl protease that processes proteins essential for Plasmodium parasites to invade and egress from host erythrocytes during the symptomatic asexual stage of malaria. PMX substrates possess a conserved cleavage region denoted by the consensus motif, SFhE (h=hydrophobic amino acid). Peptidomimetics reflecting the P3 -P1 positions of the consensus motif were designed and showed potent and selective inhibition of PMX. It was established that PMX prefers Phe in the P1 position, di-substitution at the β-carbon of the P2 moiety and a hydrophobic P3 group which was supported by modelling of the peptidomimetics in complex with PMX. The peptidomimetics were shown to arrest asexual P. falciparum parasites at the schizont stage by impairing PMX substrate processing. Overall, the peptidomimetics described will assist in further understanding PMX substrate specificity and have the potential to act as a template for future antimalarial design.
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    The Surface Area to Volume Ratio Changes the Pharmacokinetic and Pharmacodynamic Parameters in the Subcutaneous Tissue Cage Model: As Illustrated by Carprofen in Sheep
    Munn, R ; Whittem, T ; Woodward, AP (FRONTIERS MEDIA SA, 2022-07-01)
    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.