@misc{hobbs_bayless_sheats_2024, title={A Comparative Review of Cytokines and Cytokine Targeting in Sepsis: From Humans to Horses}, volume={13}, ISSN={["2073-4409"]}, url={https://doi.org/10.3390/cells13171489}, DOI={10.3390/cells13171489}, abstractNote={With the emergence of COVID-19, there is an increased focus in human literature on cytokine production, the implications of cytokine overproduction, and the development of novel cytokine-targeting therapies for use during sepsis. In addition to viral infections such as COVID-19, bacterial infections resulting in exposure to endotoxins and exotoxins in humans can also lead to sepsis, resulting in organ failure and death. Like humans, horses are exquisitely sensitive to endotoxin and are among the veterinary species that develop clinical sepsis similar to humans. These similarities suggest that horses may serve as a naturally occurring model of human sepsis. Indeed, evidence shows that both species experience cytokine dysregulation, severe neutropenia, the formation of neutrophil extracellular traps, and decreased perfusion parameters during sepsis. Sepsis treatments that target cytokines in both species include hemoperfusion therapy, steroids, antioxidants, and immunomodulation therapy. This review will present the shared cytokine physiology across humans and horses as well as historical and updated perspectives on cytokine-targeting therapy. Finally, this review will discuss the potential benefits of increased knowledge of equine cytokine mechanisms and their potential positive impact on human medicine.}, number={17}, journal={CELLS}, author={Hobbs, Kallie J. and Bayless, Rosemary and Sheats, M. Katie}, year={2024}, month={Sep} }
 @article{bayless_cooper_sheats_2024, title={Extracted Plasma Cell-Free DNA Concentrations Are Elevated in Colic Patients with Systemic Inflammation}, volume={11}, ISSN={["2306-7381"]}, url={https://doi.org/10.3390/vetsci11090427}, DOI={10.3390/vetsci11090427}, abstractNote={Colic is a common and potentially life-threatening condition in horses; in many cases, it remains challenging for clinicians to determine the cause, appropriate treatment, and prognosis. One approach that could improve patient care and outcomes is identification of novel diagnostic and prognostic biomarkers. Plasma cell-free DNA (cfDNA) is a biomarker that shows promise for characterizing disease severity and predicting survival in humans with acute abdominal pain or requiring emergency abdominal surgery. In horses, we recently determined that extracted plasma cfDNA concentrations are elevated in colic patients compared to healthy controls. For this current study, we hypothesized that extracted plasma cfDNA concentrations would be significantly higher in horses with strangulating or inflammatory colic lesions, in colic patients with systemic inflammatory response syndrome (SIRS), and in non-survivors. Cell-free DNA concentrations were measured in extracted plasma samples using a compact, portable Qubit fluorometer. Colic patients that met published criteria for equine SIRS had significantly higher median extracted plasma cfDNA compared to non-SIRS colic patients. There were no significant differences in extracted plasma cfDNA concentrations between other groups of interest. Our data offer early evidence that extracted plasma cfDNA concentration may provide information about systemic inflammation in colic patients, and additional research is warranted to expand on these findings.}, number={9}, journal={VETERINARY SCIENCES}, author={Bayless, Rosemary L. and Cooper, Bethanie L. and Sheats, M. Katie}, year={2024}, month={Sep} }
 @misc{woodrow_sheats_cooper_bayless_2023, title={Asthma: The Use of Animal Models and Their Translational Utility}, volume={12}, ISSN={["2073-4409"]}, url={https://doi.org/10.3390/cells12071091}, DOI={10.3390/cells12071091}, abstractNote={Asthma is characterized by chronic lower airway inflammation that results in airway remodeling, which can lead to a permanent decrease in lung function. The pathophysiology driving the development of asthma is complex and heterogenous. Animal models have been and continue to be essential for the discovery of molecular pathways driving the pathophysiology of asthma and novel therapeutic approaches. Animal models of asthma may be induced or naturally occurring. Species used to study asthma include mouse, rat, guinea pig, cat, dog, sheep, horse, and nonhuman primate. Some of the aspects to consider when evaluating any of these asthma models are cost, labor, reagent availability, regulatory burden, relevance to natural disease in humans, type of lower airway inflammation, biological samples available for testing, and ultimately whether the model can answer the research question(s). This review aims to discuss the animal models most available for asthma investigation, with an emphasis on describing the inciting antigen/allergen, inflammatory response induced, and its translation to human asthma.}, number={7}, journal={CELLS}, author={Woodrow, Jane Seymour and Sheats, M. Katie and Cooper, Bethanie and Bayless, Rosemary}, year={2023}, month={Apr} }
 @article{bayless_cooper_sheats_2022, title={Investigation of plasma cell-free DNA as a potential biomarker in horses}, volume={34}, ISSN={["1943-4936"]}, url={https://doi.org/10.1177/10406387221078047}, DOI={10.1177/10406387221078047}, abstractNote={ Plasma cell-free DNA (cfDNA) is a biomarker of ischemia, systemic inflammation, and mortality in humans with gastrointestinal disease. Cell-free DNA has not been investigated as a biomarker for equine colic, to our knowledge. We hypothesized that cfDNA could be measured accurately in neat equine plasma using a benchtop fluorometer and that plasma cfDNA would be elevated in emergency patients compared to healthy horses. Plasma was obtained from blood collected in Roche DNA stabilizing tubes. We used the Qubit 4 fluorometer and 1× dsDNA HS assay kit to measure cfDNA concentration in neat patient plasma and following DNA extraction of plasma with a commercial kit. Assay precision and linearity of dilution were satisfactory for neat plasma cfDNA, but DNA spike and recovery results were variable. Further, cfDNA concentrations in paired neat plasma and extracted-plasma samples ( n = 66) were not correlated. Median extracted-plasma cfDNA was higher in emergency patients ( n = 50) and a subgroup of colic patients ( n = 36), compared to healthy horses ( n = 19). Our results with extracted-plasma samples provide proof of concept for further investigation of plasma cfDNA as a biomarker in horses. }, number={3}, journal={JOURNAL OF VETERINARY DIAGNOSTIC INVESTIGATION}, publisher={SAGE Publications}, author={Bayless, Rosemary L. and Cooper, Bethanie L. and Sheats, M. Katie}, year={2022}, month={Feb} }
 @article{bayless_bayless_sheats_jones_2022, title={Withaferin A Inhibits Neutrophil Adhesion, Migration, and Respiratory Burst and Promotes Timely Neutrophil Apoptosis}, volume={9}, ISSN={["2297-1769"]}, url={https://europepmc.org/articles/PMC9247543}, DOI={10.3389/fvets.2022.900453}, abstractNote={Neutrophils play a major role in many equine conditions, including equine asthma, laminitis, and intestinal ischemia and reperfusion injury, and therefore represent an attractive target for innovative therapeutic approaches. Novel strategies for reducing neutrophilic inflammation include modulation of neutrophil functions and lifespan. Withaferin A (WFA) is a phytochemical with well-establishedin vitroandin vivoanti-inflammatory properties, but its direct effects on neutrophils are largely unknown. We hypothesized that WFA would inhibit adhesion, migration, and respiratory burst by equine neutrophils and promote timely apoptosis of primed equine neutrophils. Consistent with this hypothesis, our data show that WFA causes a significant, concentration-dependent inhibition of equine neutrophil adhesion, migration, and respiratory burst in response to diverse stimuli. Further, WFA treatment increased apoptosis of equine neutrophils exposed to GM-CSF for 24 h. This pro-apoptotic effect of WFA was not observed in unprimed neutrophils, nor at the 2-h time point relevant to our functional neutrophil experiments. Our data demonstrate that WFA may reduce neutrophil-mediated inflammation through multiple mechanisms, including suppression of inflammatory responses and promotion of apoptosis. Additional research is needed to elucidate the molecular mechanisms for these effects and evaluate the potential clinical use of WFA in veterinary and human patients.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Bayless, Rosemary and Bayless, RL and Sheats, M. Katie and Jones, Sam}, editor={Bayless, RosemaryEditor}, year={2022}, month={Jun} }
 @article{pezzanite_easley_bayless_aldrich_nelson_seim_nout-lomas_2021, title={Outcomes after cervical vertebral interbody fusion using an interbody fusion device and polyaxial pedicle screw and rod construct in 10 horses (2015-2019)}, volume={5}, ISSN={["2042-3306"]}, url={https://doi.org/10.1111/evj.13449}, DOI={10.1111/evj.13449}, abstractNote={AbstractBackgroundFurther development of surgical techniques for equine cervical stabilisation is necessary to make the procedure less technically demanding, reduce complications and improve outcomes.ObjectiveTo describe clinical outcomes and owner reports in horses undergoing placement of an interbody fusion device and polyaxial pedicle screw and rod construct for cervical vertebral fusion in horses with cervical vertebral compressive myelopathy.Study designRetrospective case series.MethodsData were retrieved from medical records of 10 horses undergoing cervical vertebral fusion (2015‐2019). Records were evaluated for signalment, duration of clinical signs, number and location of compression sites, grade of ataxia, duration of hospitalisation and complications. Long‐term follow‐up was obtained through clinical re‐evaluation, postoperative radiographs and owner contact.ResultsBreeds were mixed. Median age was 24 (range 12‐168) months. There were 2/10 mares, 4/10 geldings and 4/10 stallions. Preoperative grade of ataxia ranged from 1‐3/5. Fusion was performed at one (n = 3) or two (n = 7) sites. Two horses were euthanised within the first year. In 6 of 8 horses with ≥1‐year follow‐up, ataxia improved by 1‐3 grades, with an average improvement of 1.25 grades. In four horses, ataxia improved to grade 0‐1. In two horses the gait was unaffected, but neck comfort improved. Complications included seroma formation (n = 9), pain (n = 5), fever (n = 4), upper respiratory tract obstruction (n = 2), azotemia (n = 2), screw breakage (n = 2), progression of neurological signs (n = 1), Horner's Syndrome (n = 1), dysphagia (n = 1), hives (n = 1), implant infection (n = 1) and nondisplaced fracture (n = 1).Main limitationsSmall case series, heterogeneous patient population.ConclusionsThis technique resulted in ≥1 grade gait improvement in 6/10 cases operated and 6/8 cases for which ≥1‐year follow‐up was available, similar to other methods. Fatal complications related to implant placement did not occur. This technique may represent a safer alternative to current techniques of ventral interbody fusion with similar outcomes.}, journal={EQUINE VETERINARY JOURNAL}, author={Pezzanite, Lynn M. and Easley, Jeremiah T. and Bayless, Rosemary and Aldrich, Ellison and Nelson, Brad B. and Seim, Howard B., III and Nout-Lomas, Yvette S.}, year={2021}, month={May} }
 @article{bayless_moore_hassel_byer_landolt_nout-lomas_2019, title={Equine urinary N-acetyl-beta-D-glucosaminidase assay validation and correlation with other markers of kidney injury}, volume={31}, ISSN={["1943-4936"]}, url={https://doi.org/10.1177/1040638719867124}, DOI={10.1177/1040638719867124}, abstractNote={Detection of equine acute kidney injury (AKI) is hindered by limited markers of early renal damage in horses. N-acetyl-β-D-glucosaminidase (NAG), a lysosomal enzyme in renal tubular epithelium released into urine during tubular insult, has shown promise for early identification of AKI in humans and other species. We validated an assay for NAG in equine urine and measured urinary NAG in 7 azotemic and 7 non-azotemic client-owned adult horses. The enzymatic NAG assay was validated using within- and between-run coefficients of variation (CVs), recovery following standard addition, and linearity of dilution. Intra- and inter-run CVs (21% and 3.2%, respectively), average recovery following standard addition (99–109%), and linearity under serial dilution ( R2= 0.997) were satisfactory. Urine NAG index was significantly correlated with urinary fractional excretion of sodium (FENa; ρ = 0.76, p < 0.001) and plasma creatinine (ρ = 0.74, p = 0.001). Median urine NAG indices were higher in azotemic horses ( p = 0.006), in horses with increased urinary FENa( p = 0.006), and in horses with increased urine gamma-glutamyl transferase index ( p = 0.032). Urine NAG can be measured in horses and shows positive correlation with 2 current renal biomarkers. Additional work is needed to establish normal equine reference intervals and characterize the increase of urine NAG index in horses in relation to tubular injury.}, number={5}, journal={JOURNAL OF VETERINARY DIAGNOSTIC INVESTIGATION}, publisher={SAGE Publications}, author={Bayless, Rosemary L. and Moore, A. Russell and Hassel, Diana M. and Byer, Brittney J. and Landolt, Gabriele A. and Nout-Lomas, Yvette S.}, year={2019}, month={Sep}, pages={688–695} }