@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} }
 @article{hobbs_davis_cooper_ueda_burke_sheats_2024, title={Hemadsorption extracorporeal therapy removes cytokines ex vivo in horses}, volume={85}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.24.01.0022}, abstractNote={Plasma cytokine adsorption has shown benefit as an adjunctive therapy in human sepsis but has yet to be investigated in horses. We hypothesized that ex vivo filtration of equine plasma with a novel cytokine adsorption device would significantly reduce concentrations of lipopolysaccharide-stimulated cytokines. We also hypothesized that the device would adsorb medications commonly used to treat sepsis.}, number={6}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Hobbs, Kallie J. and Davis, Jennifer L. and Cooper, Bethanie L. and Ueda, Yu and Burke, Megan J. and Sheats, Katie}, year={2024}, month={Jun} }
 @article{hobbs_cooper_dembek_sheats_2024, title={Investigation of Extracted Plasma Cell-Free DNA as a Biomarker in Foals with Sepsis}, volume={11}, ISSN={["2306-7381"]}, url={https://doi.org/10.3390/vetsci11080346}, DOI={10.3390/vetsci11080346}, abstractNote={Cell-free DNA (cfDNA) is fragmented extracellular DNA that is released from cells into various body fluids. Previously published data from adult horses supports cfDNA as a potential disease biomarker, but also shows that direct measurement in plasma is inaccurate due to matrix effect. It is currently unknown whether a similar matrix effect exists in foal plasma. Given this, the objectives of the current study were to investigate foal plasma for potential matrix effect during fluorescence measurement of cfDNA using a Qubit fluorometer, and to determine whether neat and/or extracted plasma cfDNA concentrations are significantly different in healthy, sick non-septic (SNS) or septic foals. We hypothesized that matrix effect would interfere with accurate fluorescent measurement of cfDNA in foal plasma. Further, we hypothesized that mean extracted cfDNA concentrations, and/or extracted cfDNA:neutrophil ratio, would be elevated in plasma of septic foals compared to healthy or SNS foals. Cell-free DNA was measured in neat plasma, and following DNA extraction with a commercial kit, from 60 foals. Foal plasma exhibited both autofluorescence and non-specific dye binding, confirming matrix effect. However, even with extraction, no significant difference was found in cfDNA concentrations, or cfDNA:neutrophil ratios, between healthy (sepsis score ≤ 5), SNS (sepsis score 6–11 and negative blood culture), or septic (sepsis score ≥ 12 ± positive blood culture) foals. Our data show that matrix effect interferes with accurate Qubit measurement of cfDNA in foal plasma and supports previous findings that plasma cfDNA concentrations are not associated with sepsis diagnosis in foals. Further research is needed to better understand neutrophil function and dysfunction in foal sepsis.}, number={8}, journal={VETERINARY SCIENCES}, author={Hobbs, Kallie J. and Cooper, Bethanie L. and Dembek, Katarzyna and Sheats, M. Katie}, year={2024}, month={Aug} }
 @article{conley_brown_westerman_elfenbein_sheats_2024, title={MARCKS Inhibition Alters Bovine Neutrophil Responses to <i>Salmonella</i> Typhimurium}, volume={12}, ISSN={["2227-9059"]}, url={https://www.mdpi.com/2227-9059/12/2/442}, DOI={10.3390/biomedicines12020442}, abstractNote={Neutrophils are innate immune cells that respond quickly to sites of bacterial infection and play an essential role in host defense. Interestingly, some bacterial pathogens benefit from exuberant neutrophil inflammation. Salmonella is one such pathogen that can utilize the toxic mediators released by neutrophils to colonize the intestine and cause enterocolitis. Because neutrophils can aid gut colonization during Salmonella infection, neutrophils represent a potential host-directed therapeutic target. Myristoylated alanine-rich C-kinase substrate (MARCKS) is an actin-binding protein that plays an essential role in many neutrophil effector responses. We hypothesized that inhibition of MARCKS protein would alter bovine neutrophil responses to Salmonella Typhimurium (STm) ex vivo. We used a MARCKS inhibitor peptide to investigate the role of MARCKS in neutrophil responses to STm. This study demonstrates that MARCKS inhibition attenuated STm-induced neutrophil adhesion and chemotaxis. Interestingly, MARCKS inhibition also enhanced neutrophil phagocytosis and respiratory burst in response to STm. This is the first report describing the role of MARCKS protein in neutrophil antibacterial responses.}, number={2}, journal={BIOMEDICINES}, author={Conley, Haleigh E. and Brown, Chalise F. and Westerman, Trina L. and Elfenbein, Johanna R. and Sheats, M. Katie}, year={2024}, month={Feb} }
 @article{erin k. o'neil_fogle_sheats_love_2024, title={Opinions regarding equine veterinarian attire and attributes: results of a horse owner survey}, volume={262}, ISSN={["1943-569X"]}, DOI={10.2460/javma.24.02.0083}, abstractNote={Abstract OBJECTIVE To investigate potential equine clients’ perceptions of equine veterinarians based on attire. SAMPLE 763 horse owners/lessees. METHODS Participants were invited to complete a survey shared mainly via equestrian social media pages between August and October 2022. 1–3 Survey participants were shown pictures of a male veterinarian and a female veterinarian in 7 outfits ranging from casual to business attire and were asked to score the veterinarian on 7 traits: easygoing attitude, friendliness, compassion, trustworthiness, professionalism, competence, and cost of services. The survey asked which of the traits were most valued in an equine veterinarian, as well as whether various aspects of appearance including tattoos, piercings, and hair dyed a nonorganic color were acceptable for equine veterinarians. RESULTS Of the 2,655 individuals who opened the survey, 763 responses were included. Respondents were predominantly female (743/763 [97.4%]) from rural areas (493/763 [64.6%]). Only 37.1% (283/763) of respondents agreed that what a veterinarian wears influences their confidence in them. The highest-ranked traits in an equine veterinarian were knowledge/competency (mean ± SD, 1.46 ± 0.98), followed by trustworthiness (2.34 ± 1.08) and compassion (3.50 ± 1.20), with coveralls and scrubs being the preferred attire clients associated with these attributes (with the exception of compassion, for which polo shirt/jeans was the preferred attire). T-shirt/jeans was consistently ranked lowest by respondents in association with these attributes, except in the area of compassion, where polo shirt/black pants was ranked lowest. CLINICAL RELEVANCE Our findings suggested the attire and appearance of equine veterinarians can impact client perceptions, with veterinarians wearing scrubs and coveralls associated with higher competency and trustworthiness.}, number={8}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Erin K. O'Neil and Fogle, Callie A. and Sheats, M. Katie and Love, Kim}, year={2024}, month={Aug} }
 @article{hobbs_le sueur_hallowell_martin_sheats_ueda_2024, title={Use of extracorporeal hemoperfusion therapy in an adult horse with <i>Clostridioides difficile</i> colitis and severe systemic inflammatory response syndrome}, volume={8}, ISSN={["1939-1676"]}, url={https://doi.org/10.1111/jvim.17154}, DOI={10.1111/jvim.17154}, abstractNote={An 8-year-old American Quarter Horse gelding was treated with extracorporeal hemoperfusion (HP) therapy for treatment of Clostridioides difficile (C. difficile) colitis-induced systemic inflammatory response syndrome (SIRS). The gelding developed C. difficile associated peracute colitis and severe SIRS as evidenced by a positive fecal C. difficile PCR and tachypnea, tachycardia, fever, neutropenia, altered mucous membrane color, and hyperlactatemia. Concurrent acute kidney injury in the horse limited the use of routine anti-inflammatory and anti-lipopolysaccharide treatments, including flunixin meglumine and polymyxin B, because of potential for nephrosis. Extracorporeal HP therapy was performed twice within 48 hours of the onset of severe SIRS during which the horse's physical examination variables stabilized. The horse was euthanized after 4 days because of laminitis. These findings support further investigation of extracorporeal HP therapy as an adjunctive treatment for severe SIRS/sepsis in horses.}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Hobbs, Kallie J. and Le Sueur, Andre N. V. and Hallowell, Kimberly and Martin, Emily and Sheats, Mary Katherine and Ueda, Yu}, year={2024}, month={Aug} }
 @article{conley_till_berglund_jones_sheats_2023, title={A myristoylated alanine-rich C-kinase substrate (MARCKS) inhibitor peptide attenuates neutrophil outside-in & beta;(2)-integrin activation and signaling}, volume={17}, ISSN={["1933-6926"]}, url={https://doi.org/10.1080/19336918.2023.2233204}, DOI={10.1080/19336918.2023.2233204}, abstractNote={ABSTRACT MARCKS is an actin and PIP2-binding protein that plays an essential role in neutrophil migration and adhesion; however, the molecular details regarding MARCKS function in these processes remains unclear. Neutrophil adhesion and migration also require the cell surface receptors β2-integrins. We hypothesized that MARCKS inhibition would alter neutrophil β2-integrin activation and signaling. We utilized a MARCKS-targeting peptide to inhibit MARCKS in inside-out and outside-in β2-integrin activation in neutrophils. MANS-mediated MARCKS inhibition had no significant effect on inside-out β2-integrin activation. MANS treatment significantly attenuated ICAM-1/Mn2+-stimulated static adhesion, cell spreading and β2-integrin clustering, suggesting a role for MARCKS function in outside-in β2-integrin activation. Additional work is needed to better understand the molecular mechanisms of MARCKS role in outside-in β2-integrin activation and signaling.}, number={1}, journal={CELL ADHESION & MIGRATION}, author={Conley, Haleigh and Till, Rebecca L. and Berglund, Alix K. and Jones, Samuel L. and Sheats, M. Katie}, year={2023}, month={Dec}, pages={1–16} }
 @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{woodrow_hines_sommardahl_flatland_lo_wang_sheats_lennon_2023, title={Initial investigation of molecular phenotypes of airway mast cells and cytokine profiles in equine asthma}, volume={9}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2022.997139}, abstractNote={Equine asthma is a naturally occurring lung disease characterized by chronic, partially reversible airway obstruction, pulmonary remodeling, and lower airway inflammation. Asthma is currently divided into two major groups, mild to moderate asthma (mEA) and severe asthma (sEA), but further subtyping by phenotype (i.e., clinical presentation) and/or endotype (i.e., cellular mechanisms) may be warranted. For this study, we were interested in further investigation of cellular and inflammatory characteristics of EA, including airway mast cells. The purpose of this study was to: (1) compare mast cell protease mRNA expression between healthy and asthmatic horses, (2) analyze the cytokine profile present in BALF of currently defined equine asthma groups, and (3) use these data to evaluate potential biomarkers of defined asthma groups. We hypothesized that there would be significant differences in the cellular mast cell phenotypes (i.e., mucosal vs. connective tissue) and cytokine profiles in the BALF of asthmatic vs. healthy horses and across asthma groups. We assert these characteristics may inform additional subtypes of equine asthma. Adult horses were recruited from the institution's teaching herd and clinical caseload. Mast cell protease gene expression of the BALF cellular component and multiplex bead immunoassay for cytokine concentrations in the BALF supernatant were investigated. Airway mast cells primarily expressed tryptase, with low levels of chymase. No significant changes in protease expression were detected across groups. Horses with severe asthma had increased TNF-α, CXCL-8, and IFN-γ concentrations in BALF supernatant. Multidimensional analysis demonstrated healthy and mEA horses have overlapping characteristics, with sEA separating from the other groups. This difference was primarily due to BALF neutrophil and lymphocyte concentrations. These study results further inform understanding of EA immunopathology, and future studies designed to investigate asthma phenotypes and endotypes. Ultimately, a better understanding of these groups could help identify novel therapeutic strategies.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Woodrow, Jane S. and Hines, Melissa and Sommardahl, Carla and Flatland, Bente and Lo, Yancy and Wang, Zhiping and Sheats, Mary Katie and Lennon, Elizabeth M.}, year={2023}, month={Jan} }
 @article{sheats_petritz_robertson_2023, title={Investigation of a Questionnaire Used to Measure Self-Perception of Self-Regulated Learning in Veterinary Students}, volume={9}, ISSN={["1943-7218"]}, url={https://doi.org/10.3138/jvme-2023-0046}, DOI={10.3138/jvme-2023-0046}, abstractNote={ In the United States, the veterinary medical curriculum is 4 years, and at most institutions, no more than one-third of that time is devoted to clinical training, meaning that graduates must continue learning post-graduation. Additionally, practicing veterinarians must keep up with new discoveries and techniques in the veterinary medical field, and may also choose to pursue specific interests or specialties post-graduation. For these reasons, it is essential that veterinarians be competent, self-regulated, life-long learners. Despite agreement regarding the importance of self-regulated learning (SRL) for veterinary professionals, there is currently a paucity of data available on self-regulated learning in veterinary students. The Self-Regulated Learning Perception Scale (SRLPS) is a 41-item instrument that has been previously validated in other graduate student populations, including medical students. It addresses four domains of self-regulated learning including motivation and action to learning, planning and goal setting, strategies for learning, and assessment and self-directedness. For this project, we hypothesized that the SRLPS would have high reliability among veterinary students. As part of a larger online survey, 82 veterinary students (years 1–4) voluntarily completed the SRLPS. The instrument was generally internally consistent, with the dimensions “Motivation and action to learn,” “Planning and goal setting,” “Strategies for learning and assessment,” and “Lack of self-directedness” having Cronbach's alpha values of .73, .8, .87, and .63 respectively. The SRLPS could have broad applications in veterinary educational practices and research, including assessing impact of courses on professional development and/or coaching/mentoring programs and better understanding short- and long-term educational and career outcomes for veterinarians. }, journal={JOURNAL OF VETERINARY MEDICAL EDUCATION}, author={Sheats, M. Katie and Petritz, Olivia A. and Robertson, James B.}, year={2023}, month={Sep} }
 @article{sheats_petritz_robertson_2023, title={Investigation of a questionnaire used to measure self-perception of self-regulated learning in veterinary students}, journal={Journal of Veterinary Medical Education}, author={Sheats, M.K. and Petritz, O. and Robertson, J.}, year={2023}, month={May} }
 @article{phelps_palekar_conley_ferrero_driggers_linder_kullman_reif_sheats_dewitt_et al._2023, title={Legacy and emerging per- and polyfluoroalkyl substances suppress the neutrophil respiratory burst}, volume={20}, ISSN={["1547-6901"]}, url={https://doi.org/10.1080/1547691X.2023.2176953}, DOI={10.1080/1547691X.2023.2176953}, abstractNote={Abstract Per- and polyfluoroalkyl substances (PFASs) are used in a multitude of processes and products, including nonstick coatings, food wrappers, and fire-fighting foams. These chemicals are environmentally-persistent, ubiquitous, and can be detected in the serum of 98% of Americans. Despite evidence that PFASs alter adaptive immunity, few studies have investigated their effects on innate immunity. The report here presents results of studies that investigated the impact of nine environmentally-relevant PFASs [e.g. perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid potassium salt (PFOS-K), perfluorononanoic acid (PFNA), perfluorohexanoic acid (PFHxA), perfluorohexane sulfonic acid (PFHxS), perfluorobutane sulfonic acid (PFBS), ammonium perfluoro(2-methyl-3-oxahexanoate) (GenX), 7H-perfluoro-4-methyl-3,6-dioxa-octane sulfonic acid (Nafion byproduct 2), and perfluoromethoxyacetic acid sodium salt (PFMOAA-Na)] on one component of the innate immune response, the neutrophil respiratory burst. The respiratory burst is a key innate immune process by which microbicidal reactive oxygen species (ROS) are rapidly induced by neutrophils in response to pathogens; defects in the respiratory burst can increase susceptibility to infection. The study here utilized larval zebrafish, a human neutrophil-like cell line, and primary human neutrophils to ascertain whether PFAS exposure inhibits ROS production in the respiratory burst. It was observed that exposure to PFHxA and GenX suppresses the respiratory burst in zebrafish larvae and a human neutrophil-like cell line. GenX also suppressed the respiratory burst in primary human neutrophils. This report is the first to demonstrate that these PFASs suppress neutrophil function and support the utility of employing zebrafish larvae and a human cell line as screening tools to identify chemicals that may suppress human immune function.}, number={1}, journal={JOURNAL OF IMMUNOTOXICOLOGY}, author={Phelps, Drake W. and Palekar, Anika I. and Conley, Haleigh E. and Ferrero, Giuliano and Driggers, Jacob H. and Linder, Keith E. and Kullman, Seth W. and Reif, David M. and Sheats, M. Katie and DeWitt, Jamie C. and et al.}, year={2023}, month={Dec} }
 @misc{conley_sheats_2023, title={Targeting Neutrophil beta(2)-Integrins: A Review of Relevant Resources, Tools, and Methods}, volume={13}, ISSN={["2218-273X"]}, url={https://doi.org/10.3390/biom13060892}, DOI={10.3390/biom13060892}, abstractNote={Neutrophils are important innate immune cells that respond during inflammation and infection. These migratory cells utilize β2-integrin cell surface receptors to move out of the vasculature into inflamed tissues and to perform various anti-inflammatory responses. Although critical for fighting off infection, neutrophil responses can also become dysregulated and contribute to disease pathophysiology. In order to limit neutrophil-mediated damage, investigators have focused on β2-integrins as potential therapeutic targets, but so far these strategies have failed in clinical trials. As the field continues to move forward, a better understanding of β2-integrin function and signaling will aid the design of future therapeutics. Here, we provide a detailed review of resources, tools, experimental methods, and in vivo models that have been and will continue to be utilized to investigate the vitally important cell surface receptors, neutrophil β2-integrins.}, number={6}, journal={BIOMOLECULES}, author={Conley, Haleigh E. and Sheats, M. Katie}, year={2023}, month={Jun} }
 @article{bayless_cooper_sheats_2022, title={Investigation of plasma cell-free DNA as a potential biomarker in horses}, volume={2}, 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{sheats_burke_robertson_fiebrandt_fogle_2021, title={Development and Formative Evaluation of a Low-Fidelity Equine Castration Model for Veterinary Education}, volume={8}, ISSN={["2297-1769"]}, url={https://europepmc.org/articles/PMC8476848}, DOI={10.3389/fvets.2021.689243}, abstractNote={Entrustable Professional Activities (EPAs) are units of activity that early-stage professionals perform in the workplace that necessitate simultaneous integration of multiple competencies. EPA #6 requires students to perform a common surgical procedure on a stable patient, including pre-operative and post-operative management. Castration is one of the most common surgeries performed by equine primary care practitioners and is considered an “entry-level competency” for veterinary graduates entering equine private practice, however, to our knowledge there are no equine castration models available for veterinary student education. Therefore, we developed an inexpensive, low-fidelity model of equine field castration and evaluated it using a mixed-methods approach. Two different groups of students, with or without model experience, completed surveys before and after live horse castration. Students who used the model also completed model specific surveys. Videos of the students completing the model were evaluated by at least two different equine veterinary faculty using a 15-point rubric, and inter-rater reliability of the rubric was determined. After completing the model, students reflected on strengths and weaknesses of their performance. From our student survey results, we determined that student attitudes toward the model were mostly positive. Interestingly, there were several student attitudes toward the model that became significantly more favorable after live horse castration. Prior to live horse castration, there was no significant difference in confidence in model vs. no-model groups. Following live horse castration, students who used the model had higher confidence in procedure preparation and hand-ties than students who did not use the model, but they had lower scores for confidence during patient recovery. When reflecting on model castration, students most commonly cited preparation and surgical description as strengths, and ligature placement and hand-ties as weaknesses. Experts provided several suggestions to improve the model, including incorporation of emasculators and the need for better model stabilization. Our findings suggest that both students and veterinary educators feel that this low-fidelity model has educational value. Rubric performance metrics were favorable, but additional steps are needed to improve grading consistency among educators. Future research will determine whether student performance on the model is predictive of competence score during live-horse castration.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Sheats, M. Katie and Burke, Megan J. and Robertson, James B. and Fiebrandt, Katherine E. and Fogle, Callie A.}, year={2021}, month={Sep} }
 @article{davis_sheats_2021, title={Differential gene expression and Ingenuity Pathway Analysis of bronchoalveolar lavage cells from horses with mild/moderate neutrophilic or mastocytic inflammation on BAL cytology}, volume={234}, ISSN={["1873-2534"]}, url={https://doi.org/10.1016/j.vetimm.2021.110195}, DOI={10.1016/j.vetimm.2021.110195}, abstractNote={Mild to moderate equine asthma syndrome (mEAS) affects horses of all ages and breeds. To date, the etiology and pathophysiology of mEAS are active areas of research, and it remains incompletely understood whether mEAS horses with different immune cell 'signatures' on BAL cytology represent different phenotypes, distinct pathobiological mechanisms (endotypes), varied environmental conditions, disease severity, genetic predispositions, or all of the above. In this descriptive study, we compared gene expression data from BAL cells isolated from horses with normal BALF cytology (n = 5), to those isolated from horses with mild/moderate neutrophilic inflammation (n = 5), or mild/moderate mastocytic inflammation (n = 5). BAL cell protein lysates were analyzed for cytokine/chemokine levels using Multiplex Bead Immunoassay, and for select proteins using immunoblot. The transcriptome, determined by RNA-seq and analyzed with DEseq2, contained 20, 63, and 102 significantly differentially expressed genes in horses with normal vs. neutrophilic, normal vs. mastocytic, and neutrophilic vs. mastocytic BALF cytology, respectively. Pathway analyses revealed that BAL-isolated cells from horses with neutrophilic vs. normal cytology showed enrichment in inflammation pathways, and horses with mastocytic vs. normal cytology showed enrichment in pathways involved in fibrosis and allergic reaction. BAL cells from horses with mastocytic mEAS, compared to neutrophilic mEAS, showed enrichment in pathways involved in alteration of tissue structures. Cytokine analysis determined that IL-1β was significantly different in the lysates from horses with neutrophilic inflammation compared to those with normal or mastocytic BAL cytology. Immunoblot revealed significant difference in the relative level of MMP2 in horses with neutrophilic vs. mastocytic mEAS. Upregulation of mRNA transcripts involved in the IL-1 family cytokine signaling axis (IL1a, IL1b, and IL1R2) in neutrophilic mEAS, as well as KIT mRNA in mastocytic mEAS, are novel, potentially clinically relevant, findings of this study. These findings further inform our understanding of inflammatory cell subtypes in mEAS.}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, publisher={Elsevier BV}, author={Davis, Kaori Uchiumi and Sheats, M. Katie}, year={2021}, month={Apr} }
 @article{westerman_sheats_elfenbein_2021, title={Sulfate Import in Salmonella Typhimurium Impacts Bacterial Aggregation and the Respiratory Burst in Human Neutrophils}, volume={89}, ISSN={["1098-5522"]}, DOI={10.1128/IAI.00701-20}, abstractNote={During enteric salmonellosis, neutrophil-generated reactive oxygen species alter the gut microenvironment, favoring survival ofSalmonellaTyphimurium. While type 3 secretion system 1 (T3SS-1) and flagellar motility are potentSalmonellaTyphimurium agonists of the neutrophil respiratory burstin vitro,neither of these pathways alone is responsible for stimulation of a maximal respiratory burst.}, number={6}, journal={INFECTION AND IMMUNITY}, author={Westerman, T. L. and Sheats, M. K. and Elfenbein, J. R.}, year={2021}, month={Jun} }
 @article{woodrow_hines_sommardahl_flatland_davis_lo_wang_sheats_lennon_2020, title={Multidimensional Analysis of Bronchoalveolar Lavage Cytokines and Mast Cell Proteases Reveals Interferon-γ as a Key Biomarker in Equine Asthma Syndrome}, url={https://doi.org/10.1101/2020.02.24.956573}, DOI={10.1101/2020.02.24.956573}, abstractNote={AbstractNaturally-occurring equine asthma is an inflammatory lung disease characterized by chronic, partially reversible airway obstruction, pulmonary remodeling and lower airway inflammation. The cytokine profiles that distinguish asthma groups or subtypes in horses have not been systematically classified, and mast cell phenotypes, which, in human asthma, correlate with asthma type, lung function, and response to therapy, have not been well-described in horses. The purpose of this study was to: (1) compare mast cell protease mRNA expression between healthy and asthmatic horses, (2) analyze the cytokine profile present in BALF of currently defined equine asthma groups, and (3) use these data to evaluate potential biomarkers of defined asthma groups. Mast cell protease gene expression and select cytokine gene expression in cells isolated from BALF, and BALF multiplex cytokine assays were performed. Multidimensional analysis demonstrated that IFNγ differentiates severe from moderate asthma, and that TNFα and CXCL8 are key biomarkers of equine asthma subtype. Expression of chymase mRNA, a mast cell-specific protease, was significantly decreased in horses with mastocytic asthma. These results will help further define EAS immunopathology, which could improve understanding and definitions of asthma groups, while also potentially identify novel therapeutic strategies.}, author={Woodrow, Jane S. and Hines, Melissa and Sommardahl, Carla and Flatland, Bente and Davis, Kaori U. and Lo, Yancy and Wang, Zhiping and Sheats, Mary Katherine and Lennon, Elizabeth M.}, year={2020}, month={Feb} }
 @article{davis_sheats_2021, title={The Role of Neutrophils in the Pathophysiology of Asthma in Humans and Horses}, volume={44}, url={https://doi.org/10.1007/s10753-020-01362-2}, DOI={10.1007/s10753-020-01362-2}, abstractNote={Asthma is a common and debilitating chronic airway disease that affects people and horses of all ages worldwide. While asthma in humans most commonly involves an excessive type 2 immune response and eosinophilic inflammation, neutrophils have also been recognized as key players in the pathophysiology of asthma, including in the severe asthma phenotype where neutrophilic inflammation predominates. Severe equine asthma syndrome (sEAS) features prominent neutrophilic inflammation and has been increasingly used as a naturally occurring animal model for the study of human neutrophilic asthma. This comparative review examines the recent literature in order to explore the role of neutrophil inflammatory functions in the pathophysiology and immunology of asthma in humans and horses.}, number={2}, journal={Inflammation}, publisher={Springer Science and Business Media LLC}, author={Davis, Kaori Uchiumi and Sheats, M. Katie}, year={2021}, month={Apr}, pages={450–465} }
 @misc{sheats_2019, title={A Comparative Review of Equine SIRS, Sepsis, and Neutrophils}, volume={6}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2019.00069}, abstractNote={The most recent definition of sepsis in human medicine can be summarized as organ dysfunction caused by a dysregulated host response to infection. In equine medicine, although no consensus definition is available, sepsis is commonly described as a dysregulated host systemic inflammatory response to infection. Defense against host infection is the primary role of innate immune cells known as neutrophils. Neutrophils also contribute to host injury during sepsis, making them important potential targets for sepsis prevention, diagnosis, and treatment. This review will present both historical and updated perspectives on the systemic inflammatory response (SIRS) and sepsis; it will also discuss the impact of sepsis on neutrophils, and the impact of neutrophils during sepsis. Future identification of clinically relevant sepsis diagnosis and therapy depends on a more thorough understanding of disease pathogenesis across species. To gain this understanding, there is a critical need for research that utilizes a clearly defined, and consistently applied, classification system for patients diagnosed with, and at risk of developing, sepsis.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Sheats, M. Katie}, year={2019}, month={Mar} }
 @article{freese_sheats_2019, title={A Suspected Case of Rocky Mountain Spotted Fever in an Adult Horse in the Southeastern United States}, volume={78}, ISSN={["1542-7412"]}, DOI={10.1016/j.jevs.2019.05.003}, abstractNote={A 20-year-old Paint gelding was evaluated for fever of unknown origin. History and clinical signs were consistent with potential tick-borne disease. Samples were collected and submitted for tick-borne disease panel, herpes virus, complete blood count, and serum biochemistry. Based on physical examination findings and vaccination history, the gelding was treated for suspected tick-borne disease with oxytetracycline (8 mg/kg intravenously BID) for 5 days, followed by doxycycline (10 mg/kg PO BID) for an additional 5 days. Although titers to Borrelia burgdorferi, Anaplasma phagocytophilum, and Neorickettsia risticii on Days 4 and 8 were negative, the Rickettsia rickettsii titer went from 1:1,600 on Day 4 to 1:800 on Day 8, 1:100 on Day 21, and was seronegative by Day 38. Although complete blood polymerase chain reaction for Rickettsia rickettsii was negative, the clinical and serologic features of this case are extremely consistent with clinical cases of Rocky Mountain Spotted Fever (RMSF) described in both dogs and humans. Therefore, we submit this case report to document suspected clinical infection of an adult horse in the southeastern United States with Rickettsia rickettsii, the causative agent of RMSF. Other relevant differentials (i.e., Rickettsia parkeri, Theileria equi, and Babesia caballi) are also discussed.}, journal={JOURNAL OF EQUINE VETERINARY SCIENCE}, author={Freese, Stephanie and Sheats, M. Katie}, year={2019}, month={Jul}, pages={134–137} }
 @article{davis_sheats_2019, title={Bronchoalveolar Lavage Cytology Characteristics and Seasonal Changes in a Herd of Pastured Teaching Horses}, volume={6}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2019.00074}, abstractNote={Equine asthma syndrome (EAS) is a common problem that affects horses of any age. Severe EAS is reported to affect 10–20% of adult horses in the northern hemisphere, while mild/moderate EAS is reported to affect 60–100% of adult horses, depending on the population and geographic region. For both severe and mild/moderate EAS, the presence of lower airway inflammation is attributed to airborne “triggers” such as dust, mold, and bacterial components that horses encounter in hay and stable-environments; and treatment recommendations for horses with EAS often include full-time pasture turnout. The caveat to this recommendation is horses with summer-pasture associated EAS (SP-EAS), who experience allergic lower airway inflammation when exposed to summer pasture. The prevalence of EAS in horses on pasture that do not have SP-EAS has not been reported. The purpose of this study was to use bronchoalveolar lavage (BAL) cytology to determine the prevalence of EAS in a herd of pastured, adult research horses with no history of respiratory disease. The horses were members of a teaching animal herd housed on pasture in the southeastern United States and fed round-bale Bermuda-grass hay. BAL fluid (BALF) cytology was analyzed in both summer (May–August 2017) and winter (November 2017–February 2018). Similar to previous reports, the prevalence of severe EAS in our study population was 10% in summer and 4.3% in winter. The prevalence of mild/moderate EAS was 60% in summer and 87% in winter. The high prevalence of mild/moderate EAS in this population was unexpected, given the 24-h, year-round pasture environment and the lack of history of respiratory disease. Additionally, 61.1% of horses with both summer and winter data had a different BALF cytology profile between the two seasons. To the authors' knowledge, this is the first study to use BAL cytology to diagnose, and monitor changes in, EAS phenotype in pastured adult horses. These results help to inform discussions regarding prevalence of EAS in pastured, adult horses in the southeastern region of North America.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Davis, Kaori Uchiumi and Sheats, Mary Katherine}, year={2019}, month={Mar} }
 @article{sheats_davis_poole_2019, title={Comparative Review of Asthma in Farmers and Horses}, volume={19}, url={https://doi.org/10.1007/s11882-019-0882-2}, DOI={10.1007/s11882-019-0882-2}, abstractNote={Farmers are routinely exposed to organic dusts and aeroallergens that can have adverse respiratory health effects including asthma. Horses are farm-reared large animals with similar exposures and can develop equine asthma syndrome (EAS). This review aims to compare the etiology, pathophysiology, and immunology of asthma in horses compared to farmers and highlights the horse as a potential translational animal model for organic dust-induced asthma in humans. Severe EAS shares many clinical and pathological features with various phenotypes of human asthma including allergic, non-allergic, late onset, and severe asthma. EAS disease features include variable airflow obstruction, cough, airway hyperresponsiveness, airway inflammation/remodeling, neutrophilic infiltrates, excess mucus production, and chronic innate immune activation. Severe EAS is a naturally occurring and biologically relevant, translational animal disease model that could contribute to a more thorough understanding of the environmental and immunologic factors contributing to organic dust-induced asthma in humans.}, number={11}, journal={Current Allergy and Asthma Reports}, publisher={Springer Science and Business Media LLC}, author={Sheats, M. Katie and Davis, Kaori U. and Poole, Jill A.}, year={2019}, month={Nov} }
 @article{sheats_hammond_kedrowicz_2018, title={Analysis of Final Year Veterinary Students’ Telephone Communication Skills at a Veterinary Teaching Hospital}, volume={5}, ISSN={2306-7381}, url={http://dx.doi.org/10.3390/vetsci5040099}, DOI={10.3390/vetsci5040099}, abstractNote={Client communication is a core clinical skill that is taught as part of the required curriculum at many veterinary colleges. Although much client communication occurs face-to-face, telephone communication is used to provide patient updates, relay results of diagnostic tests, and check on discharged patients. This research explored fourth year veterinary medical students’ telephone communication skills. We recorded and analyzed the transcripts of 25 calls students made to clients of three different services in the Veterinary Teaching Hospital. Additionally, we explored the perspectives of veterinary educators by distributing a survey to university faculty and house officers (n = 57). Results indicate that students excelled at identifying the patient and purpose of the call and incorporating professional language and clear explanations. They require development in providing structure and incorporating core communication skills. Compared with our survey results, the student findings are at odds with clinicians’ expectations of students’ communication abilities. We conclude that additional training is required to familiarize students with expectations regarding telephone communication, including reviewing the case thoroughly, preparing to answer questions and provide explanations, following organizational protocol, and incorporating open ended questions, reflective listening, and empathy. This data will inform design, and help to measure the impact, of telephone communication education and training that will be incorporated into the existing veterinary communication curriculum.}, number={4}, journal={Veterinary Sciences}, publisher={MDPI AG}, author={Sheats, M. and Hammond, Sarah and Kedrowicz, April}, year={2018}, month={Dec}, pages={99} }
 @misc{sheats_yin_fang_park_crews_parikh_dickson_adler_2019, title={MARCKS and Lung Disease}, volume={60}, ISSN={["1535-4989"]}, DOI={10.1165/rcmb.2018-0285TR}, abstractNote={Abstract MARCKS (myristoylated alanine‐rich C kinase substrate) is a prominent PKC substrate expressed in all eukaryotic cells. It is known to bind to and cross‐link actin filaments, to serve as a bridge between Ca2+/calmodulin and PKC signaling, and to sequester the signaling molecule phosphatidylinositol 4,5‐bisphosphate in the plasma membrane. Since the mid‐1980s, this evolutionarily conserved and ubiquitously expressed protein has been associated with regulating cellular events that require dynamic actin reorganization, including cellular adhesion, migration, and exocytosis. More recently, translational studies have implicated MARCKS in the pathophysiology of a number of airway diseases, including chronic obstructive pulmonary disease, asthma, lung cancer, and acute lung injury/acute respiratory distress syndrome. This article summarizes the structure and cellular function of MARCKS (also including MARCKS family proteins and MARCKSL1 [MARCKS‐like protein 1]). Evidence for MARCKS's role in several lung diseases is discussed, as are the technological innovations that took MARCKS‐targeting strategies from theoretical to therapeutic. Descriptions and updates derived from ongoing clinical trials that are investigating inhalation of a MARCKS‐targeting peptide as therapy for patients with chronic bronchitis, lung cancer, and ARDS are provided.}, number={1}, journal={AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY}, author={Sheats, Mary K. and Yin, Qi and Fang, Shijing and Park, Joungjoa and Crews, Anne L. and Parikh, Indu and Dickson, Brian and Adler, Kenneth B.}, year={2019}, month={Jan}, pages={16–27} }
 @article{royal_sheats_kedrowicz_2018, title={Readability Evaluations of Veterinary Client Handouts and Implications for Patient Care}, volume={33}, ISSN={["1946-9837"]}, DOI={10.1053/j.tcam.2018.03.005}, abstractNote={Health literacy and readability are important considerations for veterinary medicine, as veterinarians commonly distribute brochures, leaflets and info-graphics to explain health related issues to pet owners. Educational materials that are poorly comprehended by the intended audience could result in negative, unintended consequences. Thus, the National Institutes of Health (NIH) and the American Medical Association (AMA) have recommended readability levels for text on health information be targeted between the fourth and sixth grade levels to accommodate a highly diverse public. In the context of veterinary medicine, an increased awareness among veterinary professionals and educators regarding readability scores and the tools available to generate "easy-to-read" text would likely benefit client adherence with veterinary recommendations, client satisfaction with their veterinarian, and ultimately, pet health. Therefore, the goal of this study was to evaluate the readability levels of a sample of popular client handout materials prepared expressly for veterinarians to download and distribute to their pet-owning clients. Results indicate that 9 of 10 client brochures were written above the recommended sixth grade reading level. Recommendations for improving readability are provided.}, number={2}, journal={TOPICS IN COMPANION ANIMAL MEDICINE}, publisher={Elsevier BV}, author={Royal, Kenneth D. and Sheats, M. Katie and Kedrowicz, April A.}, year={2018}, month={Jun}, pages={58–61} }
 @article{westerman_bogomolnaya_andrews-polymenis_sheats_elfenbein_2018, title={The Salmonella type-3 secretion system-1 and flagellar motility influence the neutrophil respiratory burst}, volume={13}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0203698}, abstractNote={Neutrophils are innate immune response cells designed to kill invading microorganisms. One of the mechanisms neutrophils use to kill bacteria is generation of damaging reactive oxygen species (ROS) via the respiratory burst. However, during enteric salmonellosis, neutrophil-derived ROS actually facilitates Salmonella expansion and survival in the gut. This seeming paradox led us to hypothesize that Salmonella may possess mechanisms to influence the neutrophil respiratory burst. In this work, we used an in vitro Salmonella-neutrophil co-culture model to examine the impact of enteric infection relevant virulence factors on the respiratory burst of human neutrophils. We report that neutrophils primed with granulocyte-macrophage colony stimulating factor and suspended in serum containing complement produce a robust respiratory burst when stimulated with viable STm. The magnitude of the respiratory burst increases when STm are grown under conditions to induce the expression of the type-3 secretion system-1. STm mutants lacking the type-3 secretion system-1 induce less neutrophil ROS than the virulent WT. In addition, we demonstrate that flagellar motility is a significant agonist of the neutrophil respiratory burst. Together our data demonstrate that both the type-3 secretion system-1 and flagellar motility, which are established virulence factors in enteric salmonellosis, also appear to directly influence the magnitude of the neutrophil respiratory burst in response to STm in vitro.}, number={9}, journal={PLOS ONE}, author={Westerman, Trina L. and Bogomolnaya, Lydia and Andrews-Polymenis, Helene L. and Sheats, M. Katherine and Elfenbein, Johanna R.}, year={2018}, month={Sep} }
 @article{sheats_royal_kedrowicz_2018, title={Using readability software to enhance the health literacy of equine veterinary clients: An analysis of 17 American Association of Equine Practitioners’ newsletter and website articles}, volume={51}, ISSN={0425-1644 2042-3306}, url={http://dx.doi.org/10.1111/evj.13042}, DOI={10.1111/evj.13042}, abstractNote={SummaryBackgroundVeterinarians often provide supplemental healthcare information to horse owners via newsletters and website articles. However, articles written above the reading level of the intended audience contributes to misunderstanding. To ensure that the text in equine healthcare articles and brochures is consistent with the literacy of clients, veterinarians can adopt guidelines set forth by the National Institutes of Health (NIH) and the American Medical Association (AMA) for a target 6th grade readability level.ObjectivesThe goal of this study was to evaluate the readability levels of a sample of American Association of Equine Practitioners’ (AAEP) newsletter and website articles prepared expressly for veterinarians to download and share with their clients. Examples from these handouts are used to illustrate principles and techniques veterinary professionals can use to align their writing with the literacy of their intended audience.Study designSoftware‐based readability analysis of 17 AAEP newsletter and website articles.MethodsA free online readability calculator was used to generate a consensus grade level readability score for 17 downloadable AAEP veterinary newsletter and website articles.ResultsSixteen of 17 articles were written above the recommended 6th grade reading level.Main limitationsWe propose that a 6th grade readability level, as set forth by the AMA, is a reasonable target for the diverse population that makes up veterinary clients; however, there is currently no research that establishes this target for veterinary clients and the American Veterinary Medical Association (AVMA) has yet to issue a consensus statement on the subject.ConclusionsAwareness of the issue of client literacy and use of tools such as readability analysis software can help veterinarians provide clients with ‘easy‐to‐read’ written materials that deliver a message that clients can comprehend, thus improving their health literacy and empowering them as partners in the veterinary‐client relationship.}, number={4}, journal={Equine Veterinary Journal}, publisher={Wiley}, author={Sheats, M. K. and Royal, K. and Kedrowicz, A.}, year={2018}, month={Dec}, pages={552–555} }
 @inproceedings{westerman_sheats_jones_elfenbein_2017, title={Identification of Salmonella Typhimurium genes essential to induce the neutrophil oxidative burst}, author={Westerman, T.L. and Sheats, M.K. and Jones, S.L. and Elfenbein, J.R.}, year={2017} }
 @misc{bowyer_davis_sheats_2017, title={Investigating the MARCKS protein as a novel therapeutic target for the treatment of equine asthma}, author={Bowyer, A. and Davis, K. and Sheats, M.K.}, year={2017} }
 @article{martin_till_sheats_jones_2017, title={Misoprostol Inhibits Equine Neutrophil Adhesion, Migration, and Respiratory Burst in an In Vitro Model of Inflammation}, volume={4}, ISSN={2297-1769}, url={http://dx.doi.org/10.3389/fvets.2017.00159}, DOI={10.3389/fvets.2017.00159}, abstractNote={In many equine inflammatory disease states, neutrophil activities, such as adhesion, migration, and reactive oxygen species (ROS) production become dysregulated. Dysregulated neutrophil activation causes tissue damage in horses with asthma, colitis, laminitis, and gastric glandular disease. Non-steroidal anti-inflammatory drugs do not adequately inhibit neutrophil inflammatory functions and can lead to dangerous adverse effects. Therefore, novel therapies that target mechanisms of neutrophil-mediated tissue damage are needed. One potential neutrophil-targeting therapeutic is the PGE1 analog, misoprostol. Misoprostol is a gastroprotectant that induces intracellular formation of the secondary messenger molecule cyclic AMP (cAMP), which has been shown to have anti-inflammatory effects on neutrophils. Misoprostol is currently used in horses to treat NSAID-induced gastrointestinal injury; however, its effects on equine neutrophils have not been determined. We hypothesized that treatment of equine neutrophils with misoprostol would inhibit equine neutrophil adhesion, migration, and ROS production, in vitro. We tested this hypothesis using isolated equine peripheral blood neutrophils collected from 12 healthy adult teaching/research horses of mixed breed and gender. The effect of misoprostol treatment on adhesion, migration, and respiratory burst of equine neutrophils was evaluated via fluorescence-based adhesion and chemotaxis assays, and luminol-enhanced chemiluminescence, respectively. Neutrophils were pretreated with varying concentrations of misoprostol, vehicle, or appropriate functional inhibitory controls prior to stimulation with LTB4, CXCL8, PAF, lipopolysaccharide (LPS) or immune complex (IC). This study revealed that misoprostol pretreatment significantly inhibited LTB4-induced adhesion, LTB4-, CXCL8-, and PAF-induced chemotaxis, and LPS-, IC-, and PMA-induced ROS production in a concentration-dependent manner. This data indicate that misoprostol-targeting of E-prostanoid (EP) receptors potently inhibits equine neutrophil effector functions in vitro. Additional studies are indicated to further elucidate the role of EP receptors in regulating neutrophil function. Overall, our results suggest misoprostol may hold promise as a novel anti-inflammatory therapeutic in the horse.}, journal={Frontiers in Veterinary Science}, publisher={Frontiers Media SA}, author={Martin, Emily Medlin and Till, Rebecca Louise and Sheats, Mary Katherine and Jones, Samuel L.}, year={2017}, month={Sep} }
 @article{martin_messenger_sheats_jones_2017, title={Misoprostol Inhibits Lipopolysaccharide-Induced Pro-inflammatory Cytokine Production by Equine Leukocytes}, volume={4}, ISSN={2297-1769}, url={http://dx.doi.org/10.3389/fvets.2017.00160}, DOI={10.3389/fvets.2017.00160}, abstractNote={Pro-inflammatory cytokines including tumor necrosis factor α (TNFα), IL-1β, IL-6, and IL-8 are potent immune mediators that exacerbate multiple equine diseases such as sepsis and laminitis. Unfortunately, safe and effective cytokine-targeting therapies are lacking in horses; therefore, novel mechanisms of inhibiting cytokine production are critically needed. One potential mechanism for inhibiting cytokine synthesis is elevation of intracellular cyclic AMP (cAMP). In human leukocytes, intracellular cAMP production is induced by activation of E-prostanoid (EP) receptors 2 and 4. These receptors can be targeted by the EP2/4 agonist and prostaglandin E1 analog, misoprostol. Misoprostol is currently used as a gastroprotectant in horses but has not been evaluated as a cytokine-targeting therapeutic. Thus, we hypothesized that misoprostol treatment would inhibit pro-inflammatory cytokine production by lipopolysaccharide (LPS)-stimulated equine leukocytes in an in vitro inflammation model. To test this hypothesis, equine leukocyte-rich plasma (LRP) was collected from 12 healthy adult horses and used to model LPS-mediated inflammatory signaling. LRP was treated with varying concentrations of misoprostol either before (pretreated) or following (posttreated) LPS stimulation. LRP supernatants were assayed for 23 cytokines using an equine-specific multiplex bead immunoassay. Leukocytes were isolated from LRP, and leukocyte mRNA levels of four important cytokines were evaluated via RT-PCR. Statistical differences between treatments were determined using one-way RM ANOVA (Holm–Sidak post hoc testing) or Friedman’s RM ANOVA on Ranks (SNK post hoc testing), where appropriate (p < 0.05, n = 3–6 horses). These studies revealed that misoprostol pre- and posttreatment inhibited LPS-induced TNFα and IL-6 protein production in equine leukocytes but had no effect on IL-8 protein. Interestingly, misoprostol pretreatment enhanced IL-1β protein synthesis following 6 h of LPS stimulation, while misoprostol posttreatment inhibited IL-1β protein production after 24 h of LPS stimulation. At the mRNA level, misoprostol pre- and posttreatment inhibited LPS-induced TNFα, IL-1β, and IL-6 mRNA production but did not affect IL-8 mRNA. These results indicate that misoprostol exerts anti-inflammatory effects on equine leukocytes when applied before or after a pro-inflammatory stimulus. However, the effects we observed were cytokine-specific and sometimes differed at the mRNA and protein levels. Further studies are warranted to establish the inhibitory effects of misoprostol on equine cytokine production in vivo.}, journal={Frontiers in Veterinary Science}, publisher={Frontiers Media SA}, author={Martin, Emily Medlin and Messenger, Kristen M. and Sheats, Mary Katherine and Jones, Samuel L.}, year={2017}, month={Sep} }
 @misc{westerman_sheats_jones_elfenbein_2016, title={A high-throughput in vitro system to study Salmonella-neutrophil interactions}, author={Westerman, T.L. and Sheats, M.K. and Jones, S.L. and Elfenbein, J.R.}, year={2016} }
 @misc{fogle_sheats_2016, title={Development of a Capstone Assessment Instrument for Evaluation of Fourth Year Veterinary Student History and Examination Skills}, author={Fogle, C. and Sheats, M.K.}, year={2016} }
 @inproceedings{westerman_sheats_jones_elfenbein_2016, title={Development of a neutrophil-Salmonella co-culture system to study Salmonella genes that alter the neutrophil respiratory burst}, author={Westerman, T.L. and Sheats, M.K. and Jones, S.L. and Elfenbein, J.R.}, year={2016} }
 @misc{johnson_sheats_2016, title={MARCKS protein as a therapeutic target in the treatment of recurrent airway obstruction in horses}, author={Johnson, C. and Sheats, M.K.}, year={2016} }
 @misc{sheats_fogle_2016, title={Student Perspectives on a Newly Implemented Community-Based Model of Clinical Training in Equine Primary Care: “What’s Workings and What Could be Better?}, author={Sheats, M.K. and Fogle, C.}, year={2016} }
 @article{sheats_sung_adler_jones_inflammation_2014, title={In Vitro Neutrophil Migration Requires Protein Kinase C-Delta (δ-PKC)-Mediated Myristoylated Alanine-Rich C-Kinase Substrate (MARCKS) Phosphorylation}, volume={38}, ISSN={0360-3997 1573-2576}, url={http://dx.doi.org/10.1007/s10753-014-0078-9}, DOI={10.1007/s10753-014-0078-9}, abstractNote={Dysregulated release of neutrophil reactive oxygen species and proteolytic enzymes contributes to both acute and chronic inflammatory diseases. Therefore, molecular regulators of these processes are potential targets for new anti-inflammatory therapies. We have shown previously that myristoylated alanine-rich C-kinase substrate (MARCKS), a well-known actin binding protein and protein kinase C (PKC) substrate, is a key regulator of neutrophil functions. In the current study, we investigate the role of PKC-mediated MARCKS phosphorylation in neutrophil migration and adhesion in vitro. We report that treatment of human neutrophils with the δ-PKC inhibitor rottlerin significantly attenuates f-Met-Leu-Phe (fMLF)-induced MARCKS phosphorylation (IC50 = 5.709 μM), adhesion (IC50 = 8.4 μM), and migration (IC50 = 6.7 μM), while α-, β-, and ζ-PKC inhibitors had no significant effect. We conclude that δ-PKC-mediated MARCKS phosphorylation is essential for human neutrophil migration and adhesion in vitro. These results implicate δ-PKC-mediated MARCKS phosphorylation as a key step in the inflammatory response of neutrophils.}, number={3}, journal={Inflammation}, publisher={Springer Science and Business Media LLC}, author={Sheats, M.K. and Sung, E.J. and Adler, K.B. and Jones, S.L. and Inflammation}, year={2014}, month={Dec}, pages={1126–1141} }
 @article{sheats_pescosolido_hefner_sung_adler_jones_2014, title={Myristoylated Alanine Rich C Kinase Substrate (MARCKS) is essential to β2-integrin dependent responses of equine neutrophils}, volume={160}, ISSN={0165-2427}, url={http://dx.doi.org/10.1016/j.vetimm.2014.04.009}, DOI={10.1016/j.vetimm.2014.04.009}, abstractNote={Neutrophil infiltration is a prominent feature in a number of pathologic conditions affecting horses including recurrent airway obstruction, ischemia-reperfusion injury, and laminitis. Cell signaling components involved in neutrophil migration represent targets for novel anti-inflammatory therapies. In order to migrate into tissue, neutrophils must respond to chemoattractant signals in their external environment through activation of adhesion receptors (i.e. integrins) and reorganization of the actin cytoskeleton. Myristoylated Alanine-Rich C-Kinase Substrate (MARCKS), a highly conserved actin-binding protein, has a well demonstrated role in cytoskeletal dependent cellular functions (i.e. adhesion, spreading, and migration), but the details of MARCKS involvement in these processes remain vague. We hypothesized that MARCKS serves as a link between the actin cytoskeleton and integrin function in neutrophils. Using a MARCKS-specific inhibitor peptide known as MANS on equine neutrophils in vitro, we demonstrate that inhibition of MARCKS function significantly attenuates β2-integrin-dependent neutrophil functions including migration, adhesion, and immune complex-mediated respiratory burst. The MANS peptide did not, however, inhibit the β2-integrin-independent PMA mediated respiratory burst. These results attest to the essential role of MARCKS function in regulating neutrophil responses, and strongly implicate MARCKS as a potential regulator of β2-integrins in neutrophils.}, number={3-4}, journal={Veterinary Immunology and Immunopathology}, publisher={Elsevier BV}, author={Sheats, Mary K. and Pescosolido, Kimberly C. and Hefner, Ethan M. and Sung, Eui Jae and Adler, Kenneth B. and Jones, Samuel L.}, year={2014}, month={Aug}, pages={167–176} }
 @article{ott_sung_melvin_sheats_haugh_adler_jones_2013, title={Fibroblast Migration Is Regulated by Myristoylated Alanine-Rich C-Kinase Substrate (MARCKS) Protein}, volume={8}, ISSN={["1932-6203"]}, url={http://europepmc.org/abstract/med/23840497}, DOI={10.1371/journal.pone.0066512}, abstractNote={Myristoylated alanine-rich C-kinase substrate (MARCKS) is a ubiquitously expressed substrate of protein kinase C (PKC) that is involved in reorganization of the actin cytoskeleton. We hypothesized that MARCKS is involved in regulation of fibroblast migration and addressed this hypothesis by utilizing a unique reagent developed in this laboratory, the MANS peptide. The MANS peptide is a myristoylated cell permeable peptide corresponding to the first 24-amino acids of MARCKS that inhibits MARCKS function. Treatment of NIH-3T3 fibroblasts with the MANS peptide attenuated cell migration in scratch wounding assays, while a myristoylated, missense control peptide (RNS) had no effect. Neither MANS nor RNS peptide treatment altered NIH-3T3 cell proliferation within the parameters of the scratch assay. MANS peptide treatment also resulted in inhibited NIH-3T3 chemotaxis towards the chemoattractant platelet-derived growth factor-BB (PDGF-BB), with no effect observed with RNS treatment. Live cell imaging of PDGF-BB induced chemotaxis demonstrated that MANS peptide treatment resulted in weak chemotactic fidelity compared to RNS treated cells. MANS and RNS peptides did not affect PDGF-BB induced phosphorylation of MARCKS or phosphoinositide 3-kinase (PI3K) signaling, as measured by Akt phosphorylation. Further, no difference in cell migration was observed in NIH-3T3 fibroblasts that were transfected with MARCKS siRNAs with or without MANS peptide treatment. Genetic structure-function analysis revealed that MANS peptide-mediated attenuation of NIH-3T3 cell migration does not require the presence of the myristic acid moiety on the amino-terminus. Expression of either MANS or unmyristoylated MANS (UMANS) C-terminal EGFP fusion proteins resulted in similar levels of attenuated cell migration as observed with MANS peptide treatment. These data demonstrate that MARCKS regulates cell migration and suggests that MARCKS-mediated regulation of fibroblast migration involves the MARCKS amino-terminus. Further, this data demonstrates that MANS peptide treatment inhibits MARCKS function during fibroblast migration and that MANS mediated inhibition occurs independent of myristoylation.}, number={6}, journal={PLOS ONE}, publisher={Public Library of Science (PLoS)}, author={Ott, Laura E. and Sung, Eui Jae and Melvin, Adam T. and Sheats, Mary K. and Haugh, Jason M. and Adler, Kenneth B. and Jones, Samuel L.}, editor={Aspenstrom, PontusEditor}, year={2013}, month={Jun} }
 @article{merlo_sheats_elce_hunter_breuhaus_2009, title={Outbreak of Lawsonia intracellularis on a Standardbred breeding farm in North Carolina}, volume={21}, ISSN={["2042-3292"]}, DOI={10.2746/095777309X400333}, abstractNote={SummaryLawsonia intracellularis is a cause of protein‐losing enteropathy in weanling foals commonly causing signs including diarrhoea, oedema and unthrifty appearance. It has previously been reported as sporadic cases throughout the USA, Canada and Europe. Only recently have outbreaks on a single farm location been reported. The cases reported here are an example of multiple foals on a single farm testing serologically positive for L. intracellularis. These foals ranged in severity from asymptomatic to severely hypoproteinaemic and septic; however, none of the foals ever displayed diarrhoea, which is the most common presenting sign of this disease process.}, number={4}, journal={EQUINE VETERINARY EDUCATION}, author={Merlo, J. L. and Sheats, M. K. and Elce, Y. and Hunter, S. and Breuhaus, B. A.}, year={2009}, month={Apr}, pages={179–182} }
 @article{sheats_cook_jones_blikslager_pease_2009, title={Use of ultrasound to evaluate outcome following colic surgery for equine large colon volvulus}, volume={42}, ISSN={0425-1644 2042-3306}, url={http://dx.doi.org/10.2746/042516409X456040}, DOI={10.2746/042516409X456040}, abstractNote={SummaryReasons for performing study:The post operative response of the large colon wall after a surgically corrected large colon volvulus (LCV) has not been investigated.Objectives:To use transabdominal ultrasound to monitor the post operative change in large colon wall thickness following surgical correction of LCV.Hypothesis:A prolonged period to colon wall involution is correlated with an increased rate of post operative morbidity and mortality.Methods:A prospective clinical study including horses that presented to the North Carolina State University Veterinary Teaching Hospital for colic between September 2006 and March, 2008, had surgically diagnosed and corrected LCV (at least 360°) without resection and recovered from anaesthesia. Ultrasound of the ventral large colon was performed at the time of anaesthetic recovery and every 6–8 h until the colon wall returned to normal thickness (≤5 mm). Outcome was evaluated using a one‐way ANOVA to compare average time to colon wall involution between: 1) survivors and nonsurvivors; and 2) horses that developed multiple organ dysfunction syndrome (MODS) during the post operative period and those that recovered without evidence of MODS.Results:Sixteen horses that recovered without evidence of MODS had a significantly shorter period to colon wall involution (≤5 mm) compared to those diagnosed with MODS (mean ± s.e. 19.6 h ± 2.5 and 39.7 h ± 6.7 respectively, P = 0.006). There was no significant difference in mean period to colon wall involution between survivors and nonsurvivors (26.2 ± 4.9 and 33.2 ± 7.8 h, respectively).Conclusions:A shorter time to colon wall involution was associated with decreased post operative morbidity in horses presented for surgical correction of large colon volvulus without resection.Potential relevance:Ultrasonographic monitoring of colon wall involution after surgical correction of LCV may aid in identifying those cases at risk of MODS. Further investigation of colon wall involution time using a larger number of horses is warranted.}, number={1}, journal={Equine Veterinary Journal}, publisher={Wiley}, author={Sheats, M. K. and Cook, V. L. and Jones, S. L. and Blikslager, A. T. and Pease, A. P.}, year={2009}, month={Dec}, pages={47–52} }
 @article{sheats_wetter_snyder_jones_2008, title={Disseminated large granular lymphoma in a horse}, volume={20}, ISSN={["2042-3292"]}, DOI={10.2746/095777308X343860}, abstractNote={SummaryA 21‐year‐old pony gelding presented for a 5 week history of diarrhoea, inappetance, progressive weight loss and lethargy. Differential diagnoses for chronic diarrhoea and weight loss in horses include: chronic salmonellosis, sand enteropathy, enterolith, parasitism (strongylosis, cyathostomiasis), NSAID induced ulcerative colitis, inflammatory bowel disease (granulomatous, lymphocytic‐plasmacytic or eosinophilic enterocolitis), gastrointestinal neoplasia (lymphosarcoma, squamous cell carcinoma), antibiotic associated clostridial overgrowth, altered diet or bacterial fermentation, peritonitis,Strongylus vulgarisinduced arteriopathy (now quite rare) and abdominal mass or abscess. In this gelding,ante mortemdiagnosis of CD3+intestinal large granular lymphoma was made via cytology of abdominal fluid and immunohistochemistry of a rectal muscle biopsy. This report details the clinical, cytological and immunophenotypic findings of a case of large granular lymphoma in a horse.}, number={9}, journal={EQUINE VETERINARY EDUCATION}, author={Sheats, M. K. and Wetter, A. J. N. J. and Snyder, L. A. and Jones, S. L.}, year={2008}, month={Sep}, pages={459–463} }
 @article{johansson_gardner_levine_papich_lafevers_goldman_sheets_atkins_2004, title={Pharmacokinetics and Pharmacodynamics of Furosemide after Oral Administration to Horses}, volume={18}, ISSN={0891-6640 1939-1676}, url={http://dx.doi.org/10.1111/j.1939-1676.2004.tb02614.x}, DOI={10.1111/j.1939-1676.2004.tb02614.x}, abstractNote={Furosemide is the most common diuretic drug used in horses. Furosemide is routinely administered as IV or IM bolus doses 3–4 times a day. Administration PO is often suggested as an alternative, even though documentation of absorption and efficacy in horses is lacking. This study was carried out in a randomized, crossover design and compared 8‐hour urine volume among control horses that received placebo, horses that received furosemide at 1 mg/kg PO, and horses that received furosemide at 1 mg/kg IV. Blood samples for analysis of plasma furosemide concentrations, PCV, and total solids were obtained at specific time points from treated horses. Furosemide concentrations were determined by reversed‐phase high‐performance liquid chromatography with fluorescent detection. Systemic availability of furosemide PO was poor, erratic, and variable among horses. Median systemic bioavailability was 5.4% (25th percentile, 75th percentile: 3.5, 9.6). Horses that received furosemide IV produced 7.4 L (7.1, 7.7) of urine over the 8‐hour period. The maximum plasma concentration of 0.03 |xg/mL after administration PO was not sufficient to increase urine volume compared with control horses (1.2 L [1.0, 1.4] PO versus 1.2 L [1.0, 1.4] control). There was a mild decrease in urine specific gravity within 1–2 hours after administration of furosemide PO, and urine specific gravity was significantly lower in horses treated with furosemide PO compared with control horses at the 2‐hour time point. Systemic availability of furosemide PO was poor and variable. Furosemide at 1 mg/kg PO did not induce diuresis in horses. Key words: Equine; Frusemide; Loop diuretic; Oral bioavailability.}, number={5}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Johansson, Anna M. and Gardner, Sarah Y. and Levine, Jay F. and Papich, Mark G. and LaFevers, D. Heath and Goldman, Rebecca B. and Sheets, M. Katie and Atkins, Clarke E.}, year={2004}, month={Sep}, pages={739–743} }