Scholarly Works, Large Animal Clinical Sciences

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  • Cross-Sectional Survey of Horse Owners to Assess Their Knowledge and Use of Biosecurity Practices for Equine Infectious Diseases in the United States
    White, Nathaniel A. II; Pelzel-McCluskey, Angela (MDPI, 2023-11-17)
    Horses are transported in the United States more than any other livestock species and co-mingle at various events; therefore, they are considered to be at an increased risk for infectious disease transmission. The fragmented movement of horses combined with numerous sites of co-mingling makes tracing the potential spread of a disease outbreak a necessary part of an infection control plan, both locally and nationally. The cross-movement of personnel with horses and the persistence of endemic diseases make biosecurity implementation an ongoing challenge. Although many of the risks for infection are known, there is limited documentation about the usefulness of prospective control measures. The objective of this survey was to determine horse owners’ understanding and knowledge of biosecurity practices for preventing infectious diseases in the United States. Questions covered owner demographic information, including horse use which was divided into 10 categories as follows: Pleasure/Trail Riding, Lessons/School, Western Show, English Show, Breeding, Farm/Ranch, Retired, Racing, Driving and Other. The survey was distributed by sending requests to a list of horse owner organizations, which then sent emails to their members. The email request described the survey and provided a website link to start the survey. A total of 2413 responses were collected. Analysis of the results included cross-tabulation to identify significant differences in biosecurity knowledge and awareness by horse use. Significant differences by horse use were identified for vaccination, biosecurity planning, use of isolation, disease risk, monitoring for diseases, co-mingling of horses, sanitation, medical decision making and health record requirements for horse events. In summary, the results suggest that most owners are not highly concerned about the risk of disease or the use of biosecurity. There are several biosecurity applications and techniques which can be increased and will benefit horse health and welfare. These include reliance on temperature monitoring, isolation of new horses at facilities, risks of horse mingling, entry requirements such as vaccination and health certificates at events, and an emphasis on having biosecurity plans for facilities and events where horses co-mingle. The information from this study will be used to create tools and information that horse owners and veterinarians can use to implement appropriate biosecurity practices for different types of horse uses and events.
  • Pharmacokinetics and efficacy of orally administered acetaminophen (paracetamol) in adult horses with experimentally induced endotoxemia
    Mercer, Melissa A.; Davis, Jennifer L.; McKenzie, Harold C.; Messenger, Kristen M.; Schaefer, Emily; Council-Troche, R. McAlister; Werre, Stephen R. (Wiley, 2023-03-01)
    Background: Acetaminophen has been evaluated in horses for treatment of musculoskeletal pain but not as an antipyretic. Objectives: To determine the pharmacokinetics and efficacy of acetaminophen compared to placebo and flunixin meglumine in adult horses with experimentally induced endotoxemia. Animals: Eight university owned research horses with experimentally induced endotoxemia. Methods: Randomized placebo controlled crossover study. Horses were treated with acetaminophen (30 mg/kg PO; APAP), flunixin meglumine (1.1 mg/kg, PO; FLU), and placebo (PO; PLAC) 2 hours after administration of LPS. Plasma APAP was analyzed via LC-MS/MS. Serial CBC, lactate, serum amyloid A, heart rate and rectal temperature were evaluated. Serum IL-1β, IL-6, IL-8, IL-10, and TNF-α were evaluated by an equine-specific multiplex assay. Results: Mean maximum plasma APAP concentration was 13.97 ± 2.74 μg/mL within 0.6 ± 0.3 hour after administration. At 4 and 6 hours after treatment, both APAP (P = <.001, P =.03, respectively) and FLU (P =.0045 and P <.001, respectively) had a significantly greater decrease in rectal temperature compared to placebo. FLU caused greater heart rate reduction than APAP at 4 and 6 hours (P =.004 and P =.04), and PLAC at 4 hours (P =.05) after treatment. Conclusions and Clinical Importance: The pharmacokinetics of acetaminophen in endotoxemic horses differ from those reported by previous studies in healthy horses. Acetaminophen is an option for antipyresis in clinical cases, particularly when administration of traditional NSAIDs is contraindicated.
  • Finisher lamb growth and rumen fermentation responses to the plane of nutrition and naturally occurring coccidiosis
    Sujani, Sathya; dos Reis, Barbara R.; Ellett, Mark D.; Schramm, Holly H.; Helm, Emma T.; White, Robin R. (Frontiers, 2023-04)
    The objective of the present study was to investigate the interaction of plane of nutrition and naturally occurring coccidiosis on finisher lamb growth performance, FAMACHA score, and rumen volatile fatty acid profile. The study included 30 Su olk, Dorset or Su olk x Dorset lambs and were divided into 2 groups based on their initial body weight and assigned to 2 feeding groups di ering in dietary energy intake to create lambs representing divergent growth curves due to di ering nutritional management. Lambs with naturally occurring coccidiosis and healthy lambs were present in both feeding groups making a 2 x 2 factorial arrangement of treatments, (a) high plane of nutrition (HPN) lambs with no clinical coccidiosis diagnosis (HPNH), (b) HPN lambs with clinical coccidiosis (HPNC), (c) low plane of nutrition (LPN) lambs with no clinical coccidiosis diagnosis (LPNH), (d) LPN lambs with clinical coccidiosis (LPNC). Body weight and FAMACHA scores were recorded once every 2 weeks. On d 65 of feeding, lambs were slaughtered, and rumen fluid samples were collected and analyzed for volatile fatty acid concentrations. All response variables were analyzed statistically using a linear mixed e ects model with fixed e ects for plane of nutrition, health status, and a randome ect for initial body weight nested within the pen. The total and average weight gain were not associated with planes of nutrition, health status, or the interaction. Health status had an impact on FAMACHA (c) score (P = 0.047) and concentration of isobutyrate (P = 0.037) and tended to a ect total VFA (P = 0.085) and acetate (P = 0.071) concentrations. The interaction between the plane of nutrition and the health status tended to a ect butyrate concentration (P = 0.058). These data support the conclusion that coccidiosis infection impacted on rumen fermentation in a manner independent of the plane of nutrition; however, the translation of these rumen level impacts did not translate to the production responses.
  • Effects of Bit Chewing on Gastric Emptying, Small Intestinal Transit, and Orocecal Transit Times in Clinically Normal Horses
    Patton, Molly E.; Andrews, Frank M.; Bogers, Sophie H.; Wong, David; McKenzie, Harold C.; Werre, Stephen R.; Byron, Christopher R. (MDPI, 2023-08-04)
    Ileus is a common life-threatening problem in horses, and currently available treatments may be ineffective. The purpose of this study was to determine whether bit chewing, a form of sham feeding, decreases the gastric emptying time (GET), small intestinal transit time (SITT), and total orocecal transit time (OCTT) in clinically normal horses in a prospective crossover study. Nine healthy horses were acclimated and fed a standardized diet. Following 24 h of fasting, self-contained video endoscopy capsules and acetaminophen were administered into the stomach via a nasogastric tube. Each horse underwent experimental (bit chewing for 20 min every 6 h) or control (no bit chewing) conditions, with a 3-week minimum washout period between conditions. The horses were enrolled in either part of the study until all video capsules were retrieved and/or 30 days lapsed. The video capsules were recovered from manure, and GET, SITT, and OCTT were determined from a video analysis. Bit chewing significantly decreased OCTT (p = 0.015) compared to the control conditions. Bit chewing decreased GET and SITT, but the differences were not significant. The mean (median) times determined via the video capsule analysis for the bit-chewing conditions were as follows: GET, 2.34 h (2.86 h); SITT, 3.22 h (3.65 h); and OCTT, 5.13 h (6.15 h), and for the control conditions, they were as follows: GET, 3.93 h (5 h); SITT, 3.79 h (4.4 h); and OCTT, 8.02 h (9.92 h). Bit chewing decreased OCTT in healthy horses. Because this segment of the gastrointestinal tract is frequently affected by ileus, bit chewing may be a safe and inexpensive intervention for that condition in horses. Further investigation in clinical patients with ileus is warranted.
  • Prevalence of Latent Equid Herpesvirus Type 1 in Submandibular Lymph Nodes of Horses in Virginia
    Saklou, Nadia; Pleasant, Scott; Lahmers, Kevin K.; Funk, Rebecca (MDPI, 2023-06-07)
    Equine Herpesvirus type 1 (EHV-1) typically causes mild respiratory disease, but it can also cause late-term abortion, neonatal foal death and neurologic disease. Once a horse is infected, the virus concentrates to local lymphoid tissue, where it becomes latent. The virus can be reactivated during times of stress, which can lead to the initiation of devastating outbreaks. Understanding the carriage rate of latent EHV-1 in different geographic regions is essential for managing the disease. The objective of the current study was to estimate the prevalence of latent EHV-1 and compare the frequency of each variant in the submandibular lymph nodes of horses in Virginia. Sixty-three submandibular lymph nodes were collected post-partem from horses submitted to regional labs for necropsy, and qPCR was performed. All samples were negative for the gB gene of EHV-1. The results demonstrated a low apparent prevalence of latent EHV-1 DNA in submandibular lymph nodes in this population of horses in Virginia. Despite this, the mainstay for outbreak prevention and mitigation continues to focus on minimizing risks and using appropriate and diligent biosecurity.
  • Improved Therapeutic Delivery Targeting Clinically Relevant Orthotopic Human Pancreatic Tumors Engrafted in Immunocompromised Pigs Using Ultrasound-Induced Cavitation: A Pilot Study
    Imran, Khan Mohammad; Tintera, Benjamin; Morrison, Holly A.; Tupik, Juselyn D.; Nagai-Singer, Margaret A.; Ivester, Hannah; Council-Troche, McAlister; Edwards, Michael; Coutermarsh-Ott, Sheryl; Byron, Christopher; Clark-Deener, Sherrie; Uh, Kyungjun; Lee, Kiho; Boulos, Paul; Rowe, Cliff; Coviello, Christian; Allen, Irving C. (MDPI, 2023-05-24)
    Pancreatic tumors can be resistant to drug penetration due to high interstitial fluid pressure, dense stroma, and disarrayed vasculature. Ultrasound-induced cavitation is an emerging technology that may overcome many of these limitations. Low-intensity ultrasound, coupled with co-administered cavitation nuclei consisting of gas-stabilizing sub-micron scale SonoTran Particles, is effective at increasing therapeutic antibody delivery to xenograft flank tumors in mouse models. Here, we sought to evaluate the effectiveness of this approach in situ using a large animal model that mimics human pancreatic cancer patients. Immunocompromised pigs were surgically engrafted with human Panc-1 pancreatic ductal adenocarcinoma (PDAC) tumors in targeted regions of the pancreas. These tumors were found to recapitulate many features of human PDAC tumors. Animals were intravenously injected with the common cancer therapeutics Cetuximab, gemcitabine, and paclitaxel, followed by infusion with SonoTran Particles. Select tumors in each animal were targeted with focused ultrasound to induce cavitation. Cavitation increased the intra-tumor concentrations of Cetuximab, gemcitabine, and paclitaxel by 477%, 148%, and 193%, respectively, compared to tumors that were not targeted with ultrasound in the same animals. Together, these data show that ultrasound-mediated cavitation, when delivered in combination with gas-entrapping particles, improves therapeutic delivery in pancreatic tumors under clinically relevant conditions.
  • The Clinical Pharmacology and Therapeutic Evaluation of Non-Steroidal Anti-Inflammatory Drugs in Adult Horses
    Mercer, Melissa A.; Davis, Jennifer L.; McKenzie, Harold C. (MDPI, 2023-05-10)
    This review firstly examines the underlying pathophysiology of pain and inflammation associated with orthopedic disease and endotoxemia. Then, it reviews the clinical pharmacology (pharmacokinetics and pharmacodynamics) of both conventional and non-conventional NSAIDs in the adult horse, and finally provides an overview of different modalities to evaluate the therapeutic efficacy of NSAIDs in research.
  • The effects of dexamethasone administration on physiological, behavioral, and production parameters in dairy cows after a difficult calving
    Swartz, T. H.; Bryant, D. M.; Schramm, H. H.; Duncan, A. J.; White, Robin R.; Wood, C. M.; Petersson-Wolfe, Christina S. (Elsevier, 2023-01)
    Dairy cows are predisposed to diseases during the postpartum period. Dystocia has been associated with increased risk for disease, which is likely the result of increased tissue trauma and stress during the prolonged parturition. To attenuate the inflammatory response seen in dystocic animals and improve well-being, we assessed the effects of a glucocorticoid, dexamethasone administered within 12 h after calving. Dystocia was defined as a difficult birth resulting in a prolonged calv-ing (>= 70 min after the amniotic sac appears) and was monitored through 3 video cameras in the close-up dry-cow pen. Cows meeting the dystocia definition were randomly assigned to receive a single intramuscular injection of either dexamethasone (DEX; 0.1 mg/kg of body weight; n = 43) or saline (CON, n = 44) within 12 h following a dystocic calving. Serum haptoglobin, blood beta-hydroxybutyrate (BHB) concentrations, body temperature, and several behaviors were measured for the first 7 d postpartum. Additionally, milk production and components for the first 120 d were recorded. Using a mixed model, the fixed effects of treatment, parity, calving assistance, and time, along with 2-and 3-way interactions, were analyzed with cow as a random effect. We observed that primiparous DEX cows had greater serum haptoglobin concentrations on d 3 and d 7 post-partum compared with primiparous CON cows. There was no difference between treatment groups for blood BHB concentrations and body temperature. Behavior was altered between treatments, with DEX cows having reduced activity for the first week postpartum, as well as less restlessness and increased lying times on some of the days following calving. Treatment interacted with time for milk yield, such that DEX cows produced 2.7 kg/d less milk than CON cows for the first month fol-lowing calving. The administration of dexamethasone resulted in changes in behavioral measurements, which could suggest a reduction in discomfort; however, due to the reduction in milk yield for the first month follow-ing calving, DEX administration may not be applicable for typical farm use. Additional research is needed to investigate treatments for cows experiencing dystocia without detrimental effects on milk yield.
  • Hepatitis E virus infects brain microvascular endothelial cells, crosses the blood–brain barrier, and invades the central nervous system
    Tian, Debin; Li, Wen; Heffron, C. Lynn; Wang, Bo; Mahsoub, Hassan M.; Sooryanarain, Harini; Hassebroek, Anna M.; Clark-Deener, Sherrie; LeRoith, Tanya; Meng, Xiang-Jin (Proceedings of the National Academy of Sciences, 2022-06-14)
    Hepatitis E virus (HEV) is an important but understudied zoonotic virus causing both acute and chronic viral hepatitis. A proportion of HEV-infected individuals also developed neurological diseases such as Guillain–Barre syndrome, neuralgic amyotrophy, encephalitis, and myelitis, although the mechanism remains unknown. In this study, by using an in vitro blood–brain barrier (BBB) model, we first investigated whether HEV can cross the BBB and whether the quasi-enveloped HEV virions are more permissible to the BBB than the nonenveloped virions. We found that both quasi-enveloped and nonenveloped HEVs can similarly cross the BBB and that addition of proinflammatory cytokine tumor necrosis factor alpha (TNF-α) has no significant effect on the ability of HEV to cross the BBB in vitro. To explore the possible mechanism of HEV entry across the BBB, we tested the susceptibility of human brain microvascular endothelial cells lining the BBB to HEV infection and showed that brain microvascular endothelial cells support productive HEV infection. To further confirm the in vitro observation, we conducted an experimental HEV infection study in pigs and showed that both quasi-enveloped and nonenveloped HEVs invade the central nervous system (CNS) in pigs, as HEV RNA was detected in the brain and spinal cord of infected pigs. The HEV-infected pigs with detectable viral RNA in CNS tissues had histological lesions in brain and spinal cord and significantly higher levels of proinflammatory cytokines TNF-α and interleukin 18 than the HEV-infected pigs without detectable viral RNA in CNS tissues. The findings suggest a potential mechanism of HEV-associated neuroinvasion.
  • Histotripsy Ablation in Preclinical Animal Models of Cancer and Spontaneous Tumors in Veterinary Patients: A Review
    Hendricks-Wenger, Alissa; Arnold, Lauren; Gannon, Jessica; Simon, Alex; Singh, Neha; Sheppard, Hannah; Nagai-Singer, Margaret A.; Imran, Khan Mohammed; Lee, Kiho; Clark-Deener, Sherrie; Byron, Christopher R.; Edwards, Michael R.; Larson, Martha M.; Rossmeisl, John H. Jr.; Coutermarsh-Ott, Sheryl; Eden, Kristin; Dervisis, Nikolaos G.; Klahn, Shawna L.; Tuohy, Joanne L.; Allen, Irving C.; Vlaisavljevich, Eli (IEEE, 2021-09-03)
    New therapeutic strategies are direly needed in the fight against cancer. Over the last decade, several tumor ablation strategies have emerged as stand-alone or combination therapies. Histotripsy is the first completely noninvasive, nonthermal, and nonionizing tumor ablation method. Histotripsy can produce consistent and rapid ablations, even near critical structures. Additional benefits include real-time image guidance, high precision, and the ability to treat tumors of any predetermined size and shape. Unfortunately, the lack of clinically and physiologically relevant preclinical cancer models is often a significant limitation with all focal tumor ablation strategies. The majority of studies testing histotripsy for cancer treatment have focused on small animal models, which have been critical in moving this field forward and will continue to be essential for providing mechanistic insight. While these small animal models have notable translational value, there are significant limitations in terms of scale and anatomical relevance. To address these limitations, a diverse range of large animal models and spontaneous tumor studies in veterinary patients have emerged to complement existing rodent models. These models and veterinary patients are excellent at providing realistic avenues for developing and testing histotripsy devices and techniques designed for future use in human patients. Here, we provide a review of animal models used in preclinical histotripsy studies and compare histotripsy ablation in these models using a series of original case reports across a broad spectrum of preclinical animal models and spontaneous tumors in veterinary patients.
  • Whole-genome sequencing to investigate a possible genetic basis of perosomus elumbis in a calf resulting from a consanguineous mating
    Barber, Alexa M.; Helms, Alyssa; Thompson, Riley; Whitlock, Brian K.; Steffen, David J.; Petersen, Jessica L. (Oxford University Press, 2021-12)
  • Effects of Nerve Growth Factor-β From Bull Seminal Plasma on Steroidogenesis and Angiogenic Markers of the Bovine Pre-ovulatory Follicle Wall Cell Culture
    Stewart, Jamie L.; Gao, Liying; Flaws, Jodi A.; Mercadante, Vitor R. G.; Dias, Nicholas W.; Canisso, Igor F.; Lima, Fabio S. (Frontiers, 2022-01-17)
    Nerve growth factor-beta (NGF) is critical for ovulation in the mammalian ovary and is luteotrophic when administered systemically to camelids and cattle. This study aimed to assess the direct effects of purified bovine NGF on steroidogenesis and angiogenic markers in the bovine pre-ovulatory follicle. Holstein heifers (n = 2) were synchronized with a standard protocol, and heifers with a preovulatory follicle (>= 12 mm) had the ovary containing the dominant follicle removed via colpotomy. Pre-ovulatory follicles were dissected into 24 pieces containing theca and granulosa cells that were randomly allocated into culture media supplemented with either purified bovine NGF (100 ng/mL) or untreated (control) for 72 h. The supernatant media was harvested for quantification of progesterone, testosterone, and estradiol concentrations, whereas explants were subjected to mRNA analyses to assess expression of steroidogenic and angiogenic markers. Treatment of follicle wall pieces with NGF upregulated gene expression of steroidogenic enzyme HDS17B (P = 0.04) and increased testosterone production (P < 0.01). However, NGF treatment did not alter production of progesterone (P = 0.81) or estradiol (P = 0.14). Consistently, gene expression of steroidogenic enzymes responsible for producing these hormones (STAR, CYP11A1, HSD3B, CYP17A1, CYP19A1) were unaffected by NGF treatment (P >= 0.31). Treatment with NGF downregulated gene expression of the angiogenic enzyme FGF2 (P = 0.02) but did not alter PGES (P = 0.63), VEGFA (P = 0.44), and ESR1 (P = 0.77). Collectively, these results demonstrate that NGF from seminal plasma may interact directly on the theca and granulosa cells of the bovine pre-ovulatory follicle to stimulate testosterone production, which may be secondary to theca cell proliferation. Additionally, decreased FGF2 expression in NGF-treated follicle wall cells suggests hastened onset of follicle wall cellular remodeling that occurs during early luteal development.
  • The Paratuberculosis Paradigm Examined: A Review of Host Genetic Resistance and Innate Immune Fitness in Mycobacterium avium subsp. Paratuberculosis Infection
    Kravitz, Amanda; Pelzer, Kevin; Sriranganathan, Nammalwar (Frontiers, 2021-08-13)
    Paratuberculosis, or Johne’s Disease (JD) is a debilitating chronic enteritis mainly affecting ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). This organism causes worldwide economic losses to the livestock industry, and is of public health importance due to the potential zoonotic risk between MAP and Crohn’s disease (CD) in humans. Without economical treatments, or a vaccine capable of preventing infection without causing cross-reactions with bovine tuberculosis, test-and-cullmethods for disease control are imperative. Unfortunately, difficulties in diagnostics and long subclinical stage hinder adequate control and is further complicated by variation in MAP exposure outcome. Interestingly, the majority of infections result in asymptomatic presentation and never progress to clinical disease. One contributing factor is host genetics, where polymorphisms in innate immune genes have been found to influence resistance and susceptibility to disease. Candidate genes identified across studies overlap with those found in CD and tuberculosis including; Solute carrier family 11 member 1 gene (SLC11A1), Nucleotide-binding-oligomerization domain containing gene 2 (NOD2), Major histocompatibility complex type II (MHC-II), and Toll-like receptor (TLR) genes. This review will highlight evidence supporting the vital role of these genes in MAP infection outcome, associated challenges, and implications for the future of JD research.
  • Transcriptional and Histochemical Signatures of Bone Marrow Mononuclear Cell-Mediated Resolution of Synovitis
    Menarim, Bruno C.; Ali, Hossam El-Sheikh; Loux, Shavahn C.; Scoggin, Kirsten E.; Kalbfleisch, Theodore S.; MacLeod, James N.; Dahlgren, Linda A. (Frontiers, 2021-12-08)
    Osteoarthritis (OA) may result from impaired ability of synovial macrophages to resolve joint inflammation. Increasing macrophage counts in inflamed joints through injection with bone marrow mononuclear cells (BMNC) induces lasting resolution of synovial inflammation. To uncover mechanisms by which BMNC may affect resolution, in this study, differential transcriptional signatures of BMNC in response to normal (SF) and inflamed synovial fluid (ISF) were analyzed. We demonstrate the temporal behavior of coexpressed gene networks associated with traits from related in vivo and in vitro studies. We also identified activated and inhibited signaling pathways and upstream regulators, further determining their protein expression in the synovium of inflamed joints treated with BMNC or DPBS controls. BMNC responded to ISF with an early pro-inflammatory response characterized by a short spike in the expression of a NF-ƙB- and mitogenrelated gene network. This response was associated with sustained increased expression of two gene networks comprising known drivers of resolution (IL-10, IGF-1, PPARG, isoprenoid biosynthesis). These networks were common to SF and ISF, but more highly expressed in ISF. Most highly activated pathways in ISF included the mevalonate pathway and PPAR-𝛄 signaling, with pro-resolving functional annotations that improve mitochondrial metabolism and deactivate NF-ƙB signaling. Lower expression of mevalonate kinase and phospho-PPAR-𝛄 in synovium from inflamed joints treated with BMNC, and equivalent IL-1β staining between BMNC- and DPBS-treated joints, associates with accomplished resolution in BMNC-treated joints and emphasize the intricate balance of pro- and anti-inflammatory mechanisms required for resolution. Combined, our data suggest that BMNC-mediated resolution is characterized by constitutively expressed homeostatic mechanisms, whose expression are enhanced following inflammatory stimulus. These mechanisms translate into macrophage proliferation optimizing their capacity to counteract inflammatory damage and improving their general and mitochondrial metabolism to endure oxidative stress while driving tissue repair. Such effect is largely achieved through the synthesis of several lipids that mediate recovery of homeostasis. Our study reveals candidate mechanisms by which BMNC provide lasting improvement in patients with OA and suggests further investigation on the effects of PPAR-𝛄 signaling enhancement for the treatment of arthritic conditions.
  • Evaluation of a continuous glucose monitoring system in neonatal foals
    Wong, David; Malik, Caitlin; Dembek, Katarzyna; Estell, Krista; Marchitello, Megan; Wilson, Katie (2021-07)
    Background Monitoring blood glucose concentrations is common in critically ill neonatal foals, especially septic foals and those receiving naso-esophageal feedings or IV parenteral nutrition. Glucose typically is measured using a point-of-care (POC) glucometer but requires repeated restraint and blood collections, which may cause irritation at venipuncture sites and increased demands on nursing staff. Continuous glucose monitoring systems (CGMS) may provide an accurate alternative for monitoring blood glucose concentration. Objectives To determine the correlation and accuracy of a CGMS to monitor neonatal foals' blood glucose concentrations as compared to a POC glucometer and laboratory chemistry analysis (CHEM). Animals Samples from 4 healthy and 4 ill neonatal foals. Methods A CGMS was placed on each foal, and glucose measurements acquired from this device were compared to simultaneous measurements of blood glucose concentration using a POC glucometer and CHEM. Results Two-hundred matched glucose measurements were collected from 8 neonatal foals. The mean bias (95% limits of agreement) between CGMS and CHEM, CGMS and POC glucometer, and POC glucometer and CHEM was 3.97 mg/dL (-32.5 to 40.4), 18.2 mg/dL (-28.8 to 65.2), and 22.18 mg/dL (-9.3 to 53.67), respectively. The Pearson's correlation coefficient (r) was significantly correlated among all devices: GCMS and CHEM (r = 0.81), CGMS and POC glucometer (r = 0.77) and POC glucometer-CHEM (r = 0.92). Conclusions and Clinical Importance Within the blood glucose concentration ranges in this study (78-212 mg/dL), CGMS measurements were significantly correlated with CHEM, suggesting that it is an acceptable method to provide meaningful, immediate, and continuous glucose concentration measurements in neonatal foals while eliminating the need for repeated restraint and blood collection.
  • A retrospective analysis of bull:cow ratio effects on pregnancy rates of beef cows previously enrolled in fixed-time artificial insemination protocols
    Timlin, Claire L.; Dias, Nicholas W.; Hungerford, Laura L.; Redifer, Tracey; Currin, John F.; Mercadante, Vitor R. G. (2021-07)
    This retrospective study aimed to determine if the number of cows exposed per bull affects pregnancy rates of cows returning to estrus after fixed-time artificial insemination (FTAI). Data were compiled over the course of 13 breeding seasons (six fall and seven spring seasons) between 2010 and 2017 from the Virginia Department of Corrections herd. Available records contained data from 17 farms and 324 groups of cows (average 47 cows/group). Multiparous cows and heifers (average age per group: 5.11 +/- 0.14 yr; n = 14,868) were exposed to FTAI. After FTAI, animals were placed on pasture with bulls diagnosed as fertile by a breeding soundness exam for natural service of cows who did not become pregnant to FTAI (n = 7,248; average 22 cows/group). Animals were classified as pregnant to FTAI, to natural service on first return to estrus, or to natural service on second or subsequent estrus determined by fetal aging at pregnancy diagnosis. The bull:cow ratio for the total number of cows exposed ranged from 1:9 to 1:73 with an average of 1:31. The bull:cow ratio considering only open cows exposed after FTAI ranged from 1:2 to 1:44 with an average of 1:14. There was significant negative, small correlation between the bull:cow ratio for total number of cows exposed and return to estrus pregnancy rate in fall breeding seasons (P = 0.01, r(2) = 0.04) but not in spring (P = 0.90). There was a significant negative, small correlation between bull:cow ratio of open cows exposed and pregnancy rates to first return to estrus in fall herds with a single sire (P < 0.001, r(2) = 0.11). There was no correlation in fall herds using multiple sires or spring herds (P = 0.12). Bull:cow ratio accounted for only 1-11% of variation in the pregnancy rates, thus we conclude that a decreased bull:cow ratio (up to 1:73) did not affect natural service return to estrus pregnancy rate. Cattlemen may consider a reduced number of bulls needed for natural service breeding after FTAI, which can decrease bull related costs and increase the economic feasibility of adopting FTAI protocols.
  • Engrafting Horse Immune Cells into Mouse Hosts for the Study of the Acute Equine Immune Responses
    Leeth, Caroline M.; Adkins, Janie; Hay, Alayna N.; Bogers, Sophie Helen; Potter, Ashley; Witonsky, Sharon G.; Zhu, Jing (MDPI, 2021-10-14)
    Immunological studies in the horse are frequently hampered by lack of environmental control, complicated study design, and ethical concerns when performing high risk studies. The purpose of the current study was to investigate the utility of a xenograft model for studying acute equine immune responses. Immunocompromised non obese diabetic (NOD). sudden combined immunodeficiency (scid).gamma-/- (NSG) mice were engrafted with either equine peripheral blood lymphocytes (PBLs) or equine bone marrow to determine an optimal protocol for equine lymphocyte engraftment. We found that both PBL and bone marrow grafts populated the host mice successfully. Bone marrow transplants were technically more challenging and required further processing to retard graft versus host disease. Graft vs host disease was apparent at 28 days post-PBL transfer and 56 days post-bone marrow transfer. The results of these studies support the use of mouse hosts to study acute equine immune responses and that different engraftment techniques can be used depending on the experimental design.
  • Can levamisole upregulate the equine cell-mediated macrophage (M1) dendritic cell (DC1) T-helper 1 (CD4 Th1) T-cytotoxic (CD8) immune response in vitro?
    Witonsky, Sharon G.; Buechner-Maxwell, Virginia A.; Santonastasto, Amy; Pleasant, R. Scott; Werre, Stephen R.; Wagner, Bettina; Ellison, Siobhan; Lindsay, David S. (Wiley, 2019-03-01)
    Background: Equine protozoal myeloencephalitis (EPM) is a common and devastating neurologic disease of horses in the United States. Because some EPM-affected horses have decreased immune responses, immunomodulators such as levamisole have been proposed as supplemental treatments. However, little is known about levamisole's effects or its mechanism of action in horses. Objective: Levamisole in combination with another mitogen will stimulate a macrophage 1 (M1), dendritic cell 1 (DC1), T-helper 1 (CD4 Th1), and T-cytotoxic (CD8) immune response in equine peripheral blood mononuclear cells (PBMCs) in vitro as compared to mitogen alone. Animals: Ten neurologically normal adult horses serologically negative for Sarcocystis neurona. Methods: Prospective study. Optimal conditions for levamisole were determined based on cellular proliferation. Peripheral blood mononuclear cells were then cultured using optimal conditions of mitogen and levamisole to identify the immune phenotype, based on subset-specific activation markers, intracellular cytokine production, and cytokine concentrations in cell supernatants. Subset-specific proliferation was determined using a vital stain. Results: Concanavalin A (conA) with levamisole, but not levamisole alone, resulted in a significant decrease (P <.05) in PBMC proliferation compared to conA alone. Levamisole alone did not elicit a specific immune phenotype different than that induced by conA. Conclusion and Clinical Importance: Levamisole co-cultured with conA significantly attenuated the PBMC proliferative response as compared with conA. If the mechanisms by which levamisole modulates the immune phenotype can be further defined, levamisole may have potential use in the treatment of inflammatory diseases.
  • Immunogenicity of Potomac horse fever vaccine when simultaneously co-administered with rabies vaccine in a multivalent vaccine or as two monovalent vaccines at separate sites
    McKenzie, H. C.; Funk, Rebecca A.; Trager, L.; Werre, Stephen R.; Crisman, Mark V. (Wiley, 2019-11-01)
    Background: Potomac horse fever (PHF) is a potentially fatal enterocolitis of horses caused by Neorickettsia risticii. The disease was originally recognised almost 40 years ago in the state of Maryland in the US. It is now known to occur in many areas of North America, as well as having been described in South America and Europe. Monocomponent PHF vaccines are available, but clinical protection with vaccination has been reported to be inconsistent. Objectives: This study was designed to assess the immunogenicity of a commercially available Potomac Horse Fever (PHF) vaccine when administered as either a monovalent PHF vaccine simultaneously co-administered with a separate monovalent Rabies vaccine or as a multivalent PHF/Rabies vaccine in horses. Study design: Randomised parallel group trial. Methods: Ninety-one client or University owned horses participated in this open-label randomised study, with 45 horses receiving the monovalent vaccines at separate sites and 46 receiving the multivalent vaccine at a single site. Serum PHF IFA titres were determined twice prior to vaccination and at 1, 2 and 3 months after vaccination. Results: Both vaccination protocols exhibited poor immunogenicity, with only one-third of all the animals demonstrating seroconversion, defined as an increase in titre of greater than 400 over baseline, at any time point after vaccination. The monovalent PHF vaccine exhibited significantly greater immunogenicity in terms of the number of horses exhibiting seroconversion, as compared to the multivalent vaccine, at one (20 vs. 11, P = 0.03) and two (18 vs. 9, p = 0.02) months post vaccination. The monovalent PHF vaccine also exhibited significantly greater immunogenicity in terms of the median (interquartile range) IFA titres, as compared to the multivalent vaccine, at one (800 [200–1600] vs. 400 [200–800], P = 0.009) and 2 months (400 [200–1600] vs. 400 [100–800], P = 0.02) post vaccination. There was no significant difference between groups at 3 months in either seroconversion rate or median IFA titers. Main limitations: This study did not assess the actual protective effects of PHF vaccination but rather used the serologic response to vaccination as a surrogate biomarker of immunity. Conclusions: The multivalent PHF/Rabies vaccine exhibited lower immunogenicity as compared to the monovalent PHF vaccine co-administered with a separate Rabies vaccine.
  • Short Communication: Association between neonatal calf diarrhea and lying behaviors
    Swartz, Turner H.; Schramm, Hollie H.; Petersson-Wolfe, Christina S. (Elsevier, 2020-06-01)
    The objective of this study was to determine the association of neonatal calf diarrhea (NCD) with step activity and lying behaviors in pre-weaned dairy calves. Calves were housed in individual hutches for the first 6 days of life, and then moved into a group pen. On the day of birth, calves (n = 30) were fitted with an accelerometer, and step activity and lying behaviors were recorded. Calves were assigned a fecal score (FS) twice daily using a 0 to 3 scale, and were diagnosed with NCD (n = 10) when the score was a 3. To ensure the only association noted was due to NCD, calves that had any other health complications were excluded from analyses (n = 1). Calves with NCD were pair matched by age, breed, and birthdate to a healthy calf. Day 0 was designated as the date of NCD diagnosis. Calves with NCD spent less time lying (P < 0.05) and displayed more lying bouts (P < 0.05) of a shorter duration (P < 0.01) than healthy calves. Specifically, calves with NCD displayed more lying bouts on days -7 (P < 0.05), -6 (P < 0.01), -5 (P < 0.01), -4 (P < 0.01), and -3 (P < 0.05). Similarly, lying bout duration was shorter for calves with NCD on days -6 (P < 0.05), -5 (P < 0.05), -4 (P < 0.01), and -3 (P < 0.01). Additional research is needed to examine if these tools can be used to identify diseased calves prospectively.