@article{mantooth_hancock_thompson_varghese_meritet_vrabel_hu_zaharoff_2024, title={Characterization of an Injectable Chitosan Hydrogel for the Tunable, Localized Delivery of Immunotherapeutics}, volume={10}, ISSN={["2373-9878"]}, url={https://doi.org/10.1021/acsbiomaterials.3c01580}, DOI={10.1021/acsbiomaterials.3c01580}, abstractNote={Localized delivery of immunotherapeutics within a tumor has the potential to reduce systemic toxicities and improve treatment outcomes in cancer patients. Unfortunately, local retention of therapeutics following intratumoral injection is problematic and is insufficiently considered. Dense tumor architectures and high interstitial pressures rapidly exclude injections of saline and other low-viscosity solutions. Hydrogel-based delivery systems, on the other hand, can resist shear forces that cause tumor leakage and thus stand to improve the local retention of coformulated therapeutics. The goal of the present work was to construct a novel, injectable hydrogel that could be tuned for localized immunotherapy delivery. A chitosan-based hydrogel, called XCSgel, was developed and subsequently characterized. Nuclear magnetic resonance studies were performed to describe the chemical properties of the new entity, while cryo-scanning electron microscopy allowed for visualization of the hydrogel's cross-linked network. Rheology experiments demonstrated that XCSgel was shear-thinning and self-healing. Biocompatibility studies, both in vitro and in vivo, showed that XCSgel was nontoxic and induced transient mild-to-moderate inflammation. Release studies revealed that coformulated immunotherapeutics were released over days to weeks in a charge-dependent manner. Overall, XCSgel displayed several clinically important features, including injectability, biocompatibility, and imageability. Furthermore, the properties of XCSgel could also be controlled to tune the release of coformulated immunotherapeutics.}, number={2}, journal={ACS BIOMATERIALS SCIENCE & ENGINEERING}, author={Mantooth, Siena M. and Hancock, Asher M. and Thompson, Peter M. and Varghese, P. J. George and Meritet, Danielle M. and Vrabel, Maura R. and Hu, Jingjie and Zaharoff, David A.}, year={2024}, month={Jan}, pages={905–920} }
 @article{amirsultan_lynch_meritet_nelson_2023, title={Persistent spontaneous pneumomediastinum in a dog with pulmonary fibrosis}, volume={8}, ISSN={["2052-6121"]}, DOI={10.1002/vrc2.708}, abstractNote={Abstract}, journal={VETERINARY RECORD CASE REPORTS}, author={Amirsultan, Sophia and Lynch, Alex and Meritet, Danielle and Nelson, Nathan}, year={2023}, month={Aug} }
 @article{villasenor_olagbaju_parsley_meritet_2023, title={Proliferative parathyroid lesions in captive-bred American bullfrogs (Lithobates catesbeianus) with metabolic bone disease}, volume={203}, ISSN={["1532-3129"]}, url={https://doi.org/10.1016/j.jcpa.2023.03.184}, DOI={10.1016/j.jcpa.2023.03.184}, abstractNote={Parathyroid gland lesions in anurans are infrequently reported and most often occur secondary to experimental interventions. Husbandry-related parathyroid changes have not been documented in this order of Amphibia. Three American bullfrogs (Lithobates catesbeianus) living in a captive colony were euthanized due to clinical concern for metabolic bone disease secondary to lack of consistent dietary supplementation with vitamin D3. Necropsy revealed cystic dilation and variable proliferation of unidentified structures within the cranial coelom corresponding to the anatomical location of anuran parathyroid glands. Histologically, the structures consisted of sheets and whorls of elongated cells. Immunohistochemistry for pan-cytokeratin revealed strong cytoplasmic staining and Grimelius staining identified neuroendocrine granules in the elongated cells of these structures, supportive of a parathyroid origin.}, journal={JOURNAL OF COMPARATIVE PATHOLOGY}, author={Villasenor, Adriana and Olagbaju, Tolulope and Parsley, Ashley and Meritet, Danielle}, year={2023}, month={May}, pages={1–4} }
 @article{mellinger_kibbe_rabbani_meritet_muddiman_gamcsik_2022, title={Mapping glycine uptake and its metabolic conversion to glutathione in mouse mammary tumors using functional mass spectrometry imaging}, volume={193}, ISSN={["1873-4596"]}, DOI={10.1016/j.freeradbiomed.2022.11.010}, abstractNote={Although glutathione plays a key role in cancer cell viability and therapy response there is no clear trend in relating the level of this antioxidant to clinical stage, histological grade, or therapy response in patient tumors. The likely reason is that static levels of glutathione are not a good indicator of how a tissue deals with oxidative stress. A better indicator is the functional capacity of the tissue to maintain glutathione levels in response to this stress. However, there are few methods to assess glutathione metabolic function in tissue. We have developed a novel functional mass spectrometry imaging (fMSI) method that can map the variations in the conversion of glycine to glutathione metabolic activity across tumor tissue sections by tracking the fate of three glycine isotopologues administered in a timed sequence to tumor-bearing anesthetized mice. This fMSI method generates multiple time point kinetic data for substrate uptake and glutathione production from each spatial location in the tissue. As expected, the fMSI data shows glutathione metabolic activity varies across the murine 4T1 mammary tumor. Although glutathione levels are highest at the tumor periphery there are regions of high content but low metabolic activity. The timed infusion method also detects variations in delivery of the glycine isotopologues thereby providing a measure of tissue perfusion, including evidence of intermittent perfusion, that contributes to the observed differences in metabolic activity. We believe this new approach will be an asset to linking molecular content to tissue function.}, journal={FREE RADICAL BIOLOGY AND MEDICINE}, author={Mellinger, Allyson L. and Kibbe, Russell R. and Rabbani, Zahid N. and Meritet, Danielle and Muddiman, David C. and Gamcsik, Michael P.}, year={2022}, month={Nov}, pages={677–684} }
 @article{meritet_gorman_townsend_chappell_kelly_russell_2021, title={Investigating the Effects of Error Management Training versus Error Avoidance Training on the Performance of Veterinary Students Learning Blood Smear Analysis}, volume={48}, ISSN={["1943-7218"]}, DOI={10.3138/jvme.2019-0055}, abstractNote={ Conventional veterinary training emphasizes correct methodologies, potentially failing to exploit learning opportunities that arise as a result of errors. Error management training (EMT) encourages mistakes during low-stakes training, with the intention of modifying perceptions toward errors and using them to improve performance in unfamiliar scenarios (adaptive transfer). Herein, we aimed to determine the efficacy of EMT, supplemented by a metacognitive module, for veterinary students learning blood smear preparation and interpretation. Our hypothesis was that EMT and metacognition are associated with improved adaptive transfer performance, as compared with error avoidance training (EAT). A total of 26 students were prospectively enrolled in this double-blind study. Performance was evaluated according to monolayer area, smear quality, cell identification, calculated white blood cell differential counts, and overall application/interpretation. Students were trained with normal canine blood and static photomicrographs. Participants tested 72 hours after training demonstrated improved performance in a test that directly recapitulated training (Wilcoxon matched-pairs signed-rank test; two-tailed p all ≤ .001). There were no significant differences between EAT and EMT in this test (Mann–Whitney U test and Welch’s t-test; two-tailed p ≥ .26) or in short- and long-term adaptive transfer tests ( p ≥ .22). Survey data indicate that participants found errors to be a valuable element of training, and that many felt capable of accurately reflecting on their own performance. These data suggest that EMT might produce outcomes comparable to EAT as it relates to blood smear analysis. }, number={3}, journal={JOURNAL OF VETERINARY MEDICAL EDUCATION}, author={Meritet, Danielle and Gorman, M. Elena and Townsend, Katy L. and Chappell, Patrick and Kelly, Laura and Russell, Duncan S.}, year={2021}, month={Jun}, pages={319–329} }
 @article{meritet_townsend_gorman_chappell_kelly_russell_2021, title={Investigating the Effects of Error Management Training versus Error Avoidance Training on the Performance of Veterinary Students Learning to Tie Surgical Knots}, volume={48}, ISSN={["1943-7218"]}, DOI={10.3138/jvme.2019-0012}, abstractNote={ Although errors can be a powerful impetus for learning, conventional pedagogy often emphasizes error-avoidance strategies that reward correct answers and disfavor mistakes. Error management training (EMT) takes an explicitly positive approach to errors, using them to create an active and self-directed learning environment. Using a surgical knot–tying model, we aimed to determine the efficacy of EMT among veterinary students with no prior surgical experience. We hypothesized that EMT would result in improved performance in unfamiliar scenarios (adaptive transfer) compared with an error-avoidance method. In this prospective double-blinded study, 42 students were equally divided between error avoidance training (EAT) and EMT groups. Performance in instrument- and hand-tied knots was evaluated for technique, time, number of attempts, and, when applicable, knot-leaking pressure. All participants demonstrated significant improvement between a pre-test and an analogous test 48 hours after training for all six outcomes (Wilcoxon matched pairs; two-tailed ps ≤ .013). An adaptive transfer test found no significant differences between EMT and EAT at 48 hours ( ps ≥ .053). All participants demonstrated a significant performance decline in six of eight outcomes at 7 weeks post-training ( ps ≤ .021). This decline was not significant for four of six EMT outcomes yet significant for five of six EAT outcomes. These data suggest that students trained in both EMT and EAT experience comparable gains in short-term performance, including adaptive transfer. Compared with EAT, EMT may help attenuate performance decline after a sustained period of quiescence. Educators may consider actively incorporating EMT into veterinary curricula. }, number={2}, journal={JOURNAL OF VETERINARY MEDICAL EDUCATION}, author={Meritet, Danielle and Townsend, Katy L. and Gorman, Elena and Chappell, Patrick and Kelly, Laura and Russell, Duncan S.}, year={2021}, month={Apr}, pages={228–237} }
 @article{nguyen_wagner_vrabel_mantooth_meritet_zaharoff_2021, title={Safety and Pharmacokinetics of Intravesical Chitosan/Interleukin-12 Immunotherapy in Murine Bladders}, volume={7}, ISSN={["2352-3735"]}, DOI={10.3233/BLC-211542}, abstractNote={BACKGROUND: Intravesical administration of interleukin 12 (IL-12) co-formulated with the biopolymer, chitosan (CS/IL-12), has demonstrated remarkable antitumor activity against preclinical models of bladder cancer. However, given historical concerns regarding severe toxicities associated with systemic IL-12 administration in clinical trials, it is important to evaluate the safety of intravesical CS/IL-12 prior to clinical translation. OBJECTIVE: To evaluate the pharmacokinetics as well as the local and systemic toxicities of intravesical CS/IL-12 immunotherapy in laboratory mice. METHODS: Local inflammatory responses in mouse bladders treated with intravesical IL-12 or CS/IL-12 were assessed via histopathology. Serum cytokine levels following intravesical and subcutaneous (s.c.) administrations of IL-12 or CS/IL-12 in laboratory mice were compared. Systemic toxicities were evaluated via body weight and liver enzyme levels. RESULTS: Intravesical IL-12 and CS/IL-12 treatments did not induce significant local or systemic toxicity. IL-12 dissemination and exposure from intravesical administration was significantly lower compared to s.c. injections. Weekly intravesical CS/IL-12 treatments were well-tolerated and did not result in blunted immune responses. CONCLUSIONS: Intravesical CS/IL-12 is safe and well-tolerated in mice. In particular, the lack of cystitis and acute inflammation justifies continued investigation of intravesical CS/IL-12 immunotherapy in larger animals and patients with bladder cancer.}, number={4}, journal={BLADDER CANCER}, author={Nguyen, Khue G. and Wagner, Ethan S. and Vrabel, Maura R. and Mantooth, Siena M. and Meritet, Danielle M. and Zaharoff, David A.}, year={2021}, pages={427–437} }