Doctor of Philosophy, The Ohio State University, 1983, Graduate School

Committee: Not Provided (Other) Subjects: Biology

MS, University of Cincinnati, 2022, Arts and Sciences: Biological Sciences

The inability to control one's environment is well recognized as a major stressor for all animals. As millions of cats enter United States shelters each year, they experience this exact stressor with lack of control of their surroundings. With a growing interesting in domestic cat welfare, there has been a push for understanding and improving the general housing environment, yet there remains a divided opinion on compartment size and setup. There are two main housing configurations used in shelters: a smaller single compartment where all resting, feeding, and litterbox components are located within a single small space, or a double compartment, which is larger and contains the feeding/resting areas on a separate side from the litterbox area, with a pass-through hole to connect. Shelters considering whether to house their cats in single compartment versus double compartment housing face a trade-off between the desire to maximize the number of spots available and the need to provide adequate space to cats. However, technology can be used to gather data so shelters can make data-driven decisions about housing. Technological advances have made it is possible to collect data on activity and location using autonomous methods, which reduces the intense personnel effort previously required and enables the collection of wider and larger data sets, including 24-hr monitoring. While promising, these technologies need to first be validated within their intended use. We tested two common types of these automated technologies: accelerometers to quantify activity, and radio frequency identification (RFID) to detect locations, for monitoring the domestic cat (Felis silvestris catus) in a shelter-like setting. Two cats were placed in a double compartment housing at separate times: one to evaluate activity levels via a Fitbit Zip and one to evaluate location with an RFID system. Both technologies were compared to manually scored video recordings of each animal. The results demonstrat (open full item for complete abstract)

Committee: Elizabeth Hobson Ph.D. (Committee Member); Lindsey Vansandt Ph.D. D.V.M. (Committee Member); Kathryn Kalafut Ph.D. (Committee Member); Theresa Culley Ph.D. (Committee Member) Subjects: Biology

Master of Science, The Ohio State University, 2022, Comparative and Veterinary Medicine

The microbiome of the gastrointestinal tract is a vast ecosystem that is important to host health. Imbalances in this ecosystem are involved in disease, therefore studying this relationship is important for understanding disease pathophysiology. Research in this area has rapidly expanded due to accessibility, lower costs of sequencing techniques, as well as an increased awareness of its scientific impact. Gut microbiome studies are often performed on fecal samples. In most species, acquiring fecal samples is a relatively simple way study the microbiome. However, fecal collection in cats is more complicated due to their unique husbandry and elimination behaviors. Fecal identification is challenging in group-housing and multi-cat households. Nonetheless, these samples are required for research and clinical purposes. One solution to this problem is the administration of fecal identification markers. Oral administration of crayon shavings and glitter have been used as fecal markers clinically, but their impact on the fecal microbiome is unknown. The objective of this research was to determine the impact of fecal identification markers, specifically crayon shavings and glitter, on the feline microbiome. A randomized crossover experiment was performed with six healthy sterilized purpose-bred cats who were group-housed in a dedicated research facility. Cats received either glitter or crayon shavings mixed in a feline canned adult maintenance diet for 14 days. A 14-day washout was performed between crossovers. Feces was collected daily from each cat for 16S rRNA gene sequencing (V4 region). Amplicon analysis was performed in R-studio using DADA2 and Phyloseq packages. Pairwise PERMANOVA analysis compared samples across experimental phases and marker order. Fecal identification markers were readily identified in the feces of all cats. Statistically significant changes to the microbiome were identified with marker order (p < 0.05) and across experimental phases (p < 0.05) f (open full item for complete abstract)

Committee: Jenessa Winston (Advisor); Valerie Parker (Committee Member); Adam Rudinsky (Committee Member) Subjects: Veterinary Services

Master of Science, The Ohio State University, 2020, Comparative and Veterinary Medicine

INTRODUCTION AND BACKGROUND: The initial chapters of this thesis will introduce the importance of evaluating cachexia and muscle loss in patients with chronic disease, definitions of terminology associated with muscle mass loss and disease, cellular pathways and mechanisms by which chronic kidney disease leads to loss of muscle, and current modalities by which skeletal muscle amounts can be quantified. OBJECTIVES: The aim of this study was to evaluate the intra- and inter-rater reliability of epaxial muscle cross-sectional area measurement on feline CT images and to determine the relationship between normalized epaxial muscle area (EMA) and subjective muscle condition score (MCS). METHODS: Feline transverse CT images including the junction of the 13th thoracic vertebrae/13th rib head were retrospectively reviewed. Right and left epaxial muscle circumference and vertebral body height were measured and an average normalized EMA (ratio of epaxial area:vertebral height) was calculated for each image. Measurements were performed by three individuals blinded to the clinical data and were repeated 1 month later. Intra- and inter-rater reliability of EMA was assessed with concordance correlation coefficient (CCC), and Bland-Altman analysis was performed to assess bias and limits of agreement (LoA) between and within observers at different time points. In cats for which MCS data were available, EMA was compared between differing MCSs via the Kruskal-Wallis test, with Bonferroni-corrected Wilcoxon rank-sum post-hoc analysis. RESULTS: In total, 101 CT scans met the inclusion criteria for reliability analysis, 29 of which had muscle condition information available for analysis. Intra-rater EMA CCC ranged from 0.84 to 0.99 with minimal bias (range -0.16 to 0.08) and narrow LoA. Inter-rater EMA CCC ranged from 0.87 to 0.94, bias was larger (range -0.46 to 0.66) and LoA were wider when assessed between observers. Median EMA was significantly lower in cats with severe (open full item for complete abstract)

Committee: Jessica Quimby DACVIM (Advisor); Valerie Parker DACVIM, DACVN (Committee Member); Rachel Cianciolo DACVP (Committee Member); Julie Byron DACVIM (Committee Member); Eric Green DACVR (Committee Member) Subjects: Veterinary Services

Doctor of Philosophy, The Ohio State University, 1987, Graduate School

Committee: Not Provided (Other) Subjects: Biology

Doctor of Philosophy, The Ohio State University, 1987, Graduate School

Committee: Not Provided (Other) Subjects: Health Sciences

Doctor of Philosophy, The Ohio State University, 1986, Graduate School

Committee: Not Provided (Other) Subjects: Biology

Doctor of Philosophy, The Ohio State University, 1986, Graduate School

Committee: Not Provided (Other) Subjects: Biology

Doctor of Philosophy, The Ohio State University, 1984, Graduate School

Committee: Not Provided (Other) Subjects: Biology

Doctor of Philosophy, The Ohio State University, 1983, Graduate School

Committee: Not Provided (Other) Subjects: Health Sciences

Doctor of Philosophy, The Ohio State University, 1982, Graduate School

Committee: Not Provided (Other) Subjects: Health Sciences

Doctor of Philosophy, The Ohio State University, 1977, Graduate School

Committee: Not Provided (Other) Subjects: Biology

Doctor of Philosophy, The Ohio State University, 2016, Comparative and Veterinary Medicine

Feline oral squamous cell carcinoma (FOSCC) is the most common oral cancer in cats. This cancer is very aggressive and has the ability to invade into the adjacent bone resulting in poor quality of life and a grave prognosis in affected cats. FOSCC has been shown to be comparable to human OSCC in many aspects. However, the pathogenesis of FOSCC remains unclear. Similar to human OSCC, FOSCCs respond poorly to the available standard therapy. Therefore, novel molecular targets as well as effective therapies are required for this cancer. The usefulness of p16, p53, and pRb immunohistochemistry (IHC) for human OSCC classification has been reported. Low p16 frequently associates with non-viral-associated OSCCs, while high p16 with low p53 and pRb usually occurs in HPV-associated OSCC. In addition, a favorable prognosis was found in patients with HPV-associated OSCC and a grave prognosis was observed in patients with non-viral-associated OSCC. In this study, the IHC pattern of p16, p53, and pRb in FOSCC was investigated. We found that low p16 IHC is common in FOSCCs and high p16 IHC is present in a subset of patients with this cancer. However feline papillomavirus was not detected in these samples. These results indicate that FOSCCs have more than one type of classification and a variation in pathogenesis may occur in FOSCC. Increased osteoprotegerin (OPG) has been found to reduce tumor size and bone invasion in many human bone-invasive cancers. Low levels of feline OPG (fOPG) mRNA expression were previously observed in a bone-invasive FOSCC cell line (SCCF2). The role of fOPG in bone-invasive FOSCC in vitro and in vivo was investigated using a novel bone-invasive FOSCC cell line with high fOPG mRNA expression (SCCF2-OPGv.1).We found that overexpression of fOPG reduced tumor growth and inhibited bone invasion in bone-invasive FOSCC in vivo. Thus, fOPG could be effective adjuvant therapy for FOSCC-associated bone lysis. Telomerase, a protein complex with cell immortaliz (open full item for complete abstract)

Committee: Thomas Rosol J. (Advisor) Subjects: Animal Diseases; Experiments; Molecular Biology; Veterinary Services

Master of Sciences (Engineering), Case Western Reserve University, 2016, Biomedical Engineering

Neurogenic bowel dysfunction (NBD) is a common and socially debilitating issue for people with spinal cord injury. Our lab aims to develop a new treatment approach for NBD using electrical stimulation. In order to conduct this research, we have developed instrumentation to record colon pressure and diameter in sufficient spatial resolution to quantify colon storage and excretion. We have also developed a control system to record from our instrumentation, generate electrical stimulation patterns and allow for user control during experimentation. Both the instrumentation and control system have been validated on the bench and in-vivo for real-time quantification of colonic activity. Our setup has been used to conduct feline experiments and will act as a platform for future human studies.

Committee: Kenneth Gustafson (Advisor); Dennis Bourbeau (Committee Member); Dustin Tyler (Committee Member); Abidemi Ajiboye (Committee Member) Subjects: Biomedical Engineering; Biomedical Research; Engineering

Master of Science, The Ohio State University, 2015, Comparative and Veterinary Medicine

Exenatide extended-release (ER) is a microencapsulated formulation of the GLP-1-receptor agonist exenatide. It has a protracted pharmacokinetic profile that allows a once-weekly injection with comparable efficacy to insulin and an improved safety profile in type-2 diabetic people. Here we studied the pharmacology of Exenatide-ER in 6 healthy cats. A single subcutaneous injection of Exenatide-ER (0.13 mg/kg) was administered on day 0. Exenatide concentrations were measured for 12 weeks. A hyperglycemic clamp (target = 225 mg/dL) was performed on days minus 7 (Clamp-I) and 21 (Clamp-II) with measurements of insulin and glucagon concentrations. Glucose tolerance was defined as the amount of glucose required to maintain hyperglycemia during the clamp. Continuous glucose monitoring (CGM) was performed on weeks 0, 2 and 6 post-injection. Plasma concentrations of exenatide peaked at 1 hour and 4 weeks post-injection. Comparing Clamp-1 to Clamp-2, fasting BG decreased (mean [±SD] = -11 ± 8 mg/dL, P = 0.02), glucose tolerance improved (median [range] +33% [4-138%], P = 0.04), insulin concentrations increased (+36.5% [-9.9-274.1%], P = 0.02) and glucagon concentrations decreased (-4.7% [0-12.1%], P = 0.005). Compared to pre-injection values on CGM, glucose concentrations decreased and the frequency of readings < 50 mg/dL increased at 2 and 6 weeks post-injection of Exenatide-ER. This did not correspond to clinical hypoglycemia. No other side effects were observed throughout the study. Exenatide-ER was safe and effective in improving glucose tolerance 3 weeks after a single injection. Further evaluation is needed to determine its safety, efficacy and duration of action in diabetic cats.

Committee: Chen Gilor (Advisor); Christopher Adin (Committee Member); Ramiro Toribio (Committee Member); Valerie Parker (Committee Member) Subjects: Medicine; Pharmacology; Veterinary Services

Master of Science, The Ohio State University, 2015, Comparative and Veterinary Medicine

Introduction: Signal transducer and activator of transcription 3 (STAT3) plays a critical role in tumor development by regulating signaling pathways involved in cell proliferation, survival, metastasis and angiogenesis. STAT3 is activated in many cancers, including head and neck squamous cell carcinoma (HNSCC) in people. Feline oral squamous cell carcinoma (OSCC) is similar to advanced or recurrent HNSCC as it is poorly responsive to traditional therapies and carries a poor long-term prognosis. The purpose of this study was to characterize expression and activation of STAT3 in feline OSCC cell lines and tumor samples and to investigate the biologic activity of a novel, allosteric STAT3 inhibitor, LLL12, in feline OSCC cell lines. Results: We evaluated 3 feline OSCC cell lines and one of these (SCCF2) exhibited high levels of constitutive STAT3 phosphorylation and high sensitivity to LLL12 treatment. Exposure of SCCF2 cells to LLL12 resulted in decreased expression of pSTAT3 and total STAT3, apoptosis as assessed by caspase 3/7 activation, inhibition of colony formation and reduced expression of the STAT3 transcriptional target survivin. In contrast, the STAT3 transcriptional targets VEGF and MCL-1 increased after LLL12 treatment. This was, in part, likely due to LLL12 mediated upregulation of HIF-1a, which is known to drive VEGF and MCL-1 expression. The OSCC cell lines with low basal STAT3 phosphorylation did not exhibit these effects, suggesting that STAT3 inhibition was responsible for the observed results. Lastly, immunohistochemistry for pSTAT3 was performed using a feline OSCC tissue microarray, demonstrating expression in 48% of samples tested. Conclusions: These data demonstrate that LLL12 has biologic activity against a feline OSCC cell line expressing pSTAT3 and that STAT3 represents a target for therapeutic intervention in this disease. However, given the upregulation of several STAT3 transcriptional targets following treatment, further (open full item for complete abstract)

Committee: Cheryl London (Advisor); William Kisseberth (Committee Member); Emma Warry (Committee Member) Subjects: Cellular Biology; Oncology

Master of Science, The Ohio State University, 2014, Comparative and Veterinary Medicine

GLP-1 is an intestinal hormone that induces glucose-dependent stimulation of insulin secretion while suppressing glucagon secretion and increasing beta cell mass, satiety and gastric-emptying time. Liraglutide is a fatty-acid derivative of GLP-1 with a protracted pharmacokinetic profile that is used in people for treatment of type II diabetes mellitus and obesity. The aim of this study was to determine the pharmacokinetics and pharmacodynamics of liraglutide in healthy cats. Hyperglycemic clamps were performed on days 0 (HGC) and 14(LgHGC) in eight healthy cats. Liraglutide was administered subcutaneously (0.6 mg/cat) once daily on days 8 through 14. Compared to the HGC (mean ± SD; 455.5 ± 115.8 ng/L), insulin concentrations during LgHGC were increased (760.8 ± 350.7 ng/L; P = 0.0022), glucagon concentrations decreased (0.66 ± 0.4 pmol/L during HGC vs. 0.5 ± 0.4 pmol/L during LgHGC; P = 0.0089) and there was a trend towards an increased total glucose infused [median (range) of 1.61 (1.11 – 2.54) g/kg during HGC vs. 2.25 (1.64 – 3.10) g/kg during LgHGC; P = 0.087]. Appetite reduction and decreased body weight (9% ± 3; P=0.006) were observed in all cats. Liraglutide has similar effects and pharmacokinetics profile in cats to those reported in people. With a half-life of approximately 12 hours, once daily dosing might be feasible, however significant effects on appetite and weight loss may necessitate dosage or dosing frequency reductions. Further investigation of liraglutide in diabetic cats and overweight cats is warranted.

Committee: Chen Gilor DVM, PhD, DACVIM (Advisor); Susan Johnson DVM, MS, DACVIM (Committee Member); Christopher Adin DVM, DACVS (Committee Member); Jeffrey Lakritz DVM, DACVIM (Committee Member) Subjects: Animal Diseases; Animal Sciences; Animals; Endocrinology; Veterinary Services

Bachelor of Science, Ashland University, 2014, Biology/Toxicology

Animals that are kept in captivity need enrichment activities to live better lives. There are many types of enrichment such as cognitive, auditory, and visual. This study focuses on olfactory enrichment, which was chosen because cats use their olfactory sense in communication and in hunting. This means that olfactory enrichment has a profound effect upon them. This study was done to look at olfactory enrichment for cats that were housed communally in a rescue shelter. This experiment was novel because it looked at cats that were not housed individually as was done in previous studies. The study looked at four scents: lavender, rabbit, catnip, and silver vine. The cats were housed communally, which allowed them to constantly interact with the stimulus and each other. Another novelty of this experiment was the use of silver vine as an enrichment scent, which had been used previously with big cats but not with domestic felines. The experiment measured the behavior of the cats to look at the enriching effects of the scents. The cats were videotaped while they interacted with the cloth. The frequencies of behaviors were then quantified and analyzed. It was found that lavender had a significant effect on the frequency of sitting behavior, rabbit, and catnip had no significant effects on behavior, and silver vine had a significant effect on the frequency of sitting and playing. The results of the study show that it is possible to use enrichment for cats that are housed communally in a shelter and that silver vine is an effective enrichment scent because it increased play behavior. Future studies should focus on the other benefits of silver vine and other scents that could be beneficial for cats living in a communally housed shelter.

Committee: Mason Posner PhD (Advisor); Richard Stoffer PhD (Other) Subjects: Behavioral Sciences; Biology

Master of Science, The Ohio State University, 2012, Veterinary Biosciences

Feline oral squamous cell carcinoma (FOSCC) is an aggressive head and neck cancer in cats. The survival rate for FOSCC is less than one year and little is known about the mechanisms that induce this cancer. In humans, head and neck squamous cell carcinoma (HNSCC) can be categorized as human papillomavirus (HPV)-induced and non-HPV- induced HNSCC. Non-HPV HNSCCs are associated with mutated tumor suppressor genes, especially TP53 and p16 (CDKN2A/INK4A). Immunohistochemistry (IHC) for p16 was reported to be an effective tool to classify HNSCC. Increased p16 with decreased p53 and pRb immunoreactivity were suspected to be markers of HPV-induced SCC, while decreased p16 was reported to correlate with mutations of the CDKN2A gene in non-HPV- induced HNSCC. The roles of p16 and PVs have not been investigated in FOSCC. In this study, we searched for feline domestic papillomavirus type II (FdPV2) and other PV DNA and measured p16, p53, and pRb immunoreactivity in FOSCCs. Expression of p16 mRNA was measured in 3 FOSCC cell lines (F1, F2, and F3) by quantitative reverse transcriptase PCR (Q-RT-PCR). Four published primers were used to detect PV DNA in three FOSCC cell lines and one sample from a feline Bowenoid in situ carcinoma (FBISC) was used as a positive control. Immunoreactivity for p16, p53, and pRb were also examined in 43 FOSCC paraffin-embedded biopsy specimens, three FOSCC cell line xenografts, and one FBISC. We found that 13% (6/43) of FOSCC samples had increased p16 protein for IHC, while 40% (17/43) and 46% (20/43) iii expressed low and moderate levels, respectively. Almost all FOSCC samples classified as high intensity immunostaining for p16 protein had low p53 IHC staining with moderate pRb immunoreactivity. A high level of p16 mRNA level was demonstrated in the F1 cell line, which also expressed increased p16 protein by IHC. In contrast, decreased expression of p16 immunoreactivity was found in the F2 and F3 cell lines, which had low levels of p16 mRNA. PV DNA (open full item for complete abstract)

Committee: Thomas J. Rosol PhD (Advisor); Ramiro Toribio PhD (Committee Member); Gwendolen Lorch PhD (Committee Member) Subjects: Oncology

Master of Science, The Ohio State University, 2011, Veterinary Clinical Sciences

The microcirculation consists of vessels less than ten microns in diameter. Each microcirculatory unit has a feeder arteriole, capillaries and draining venules. Traditionally, when monitoring perfusion in patients, macrocirculatory parameters such as heart rate, blood pressure, cardiac output, lactate levels and central venous oxygen saturation have been utilized. Unfortunately, research in humans and dogs has demonstrated that these macrovascular parameters show poor correlation with changes at the microvascular level and thereby may poorly reflect tissue perfusion. Newer technologies, such as sidestream dark field microscopy (SDF) allow for direct imaging of the microcirculation and the ability to evaluate changes related to various stimuli, such as anesthesia, surgery, shock, and sepsis. This technology has been validated in humans, rodents and dogs, but has not yet been explored in cats. We sought to establish baseline clinical values for microcirculatory parameters in healthy, anesthetized cats using SDF and to determine if surgical manipulation alters these values during ovariohysterectomy. Eighteen healthy cats presenting for elective ovariohysterectomy were anesthetized using a standardized protocol. Three 20-second microcirculatory videos were obtained from the sublingual mucosa at three intervention points: after induction but before placement of the first towel clamp, after ligation of the first ovarian pedicle and after placement of the final skin suture and towel clamp removal. At each time point, macrovascular parameters (heart rate, respiratory rate, blood pressure), pulse oximetry, end tidal carbon dioxide, and end tidal inhalant anesthetic concentrations were recorded. In addition, SDF videos of the microcirculation were obtained from the sublingual mucosa using previously established consensus criteria. Videos were assessed for quality; only those deemed acceptable were included. Qualifying videos were analyzed by a single observer blinded to in (open full item for complete abstract)

Committee: Edward Cooper VMD (Advisor); Richard Bednarski DVM (Committee Member); Mary McLoughlin DVM (Committee Member); Amy Butler DVM (Committee Member) Subjects: Animals; Medical Imaging; Veterinary Services