ItemA nuclear factor-kappa B inhibiting peptide suppresses innate immune receptors and gliosis in a transgenic mouse model of Alzheimer’s disease(Elsevier, 2021-06) Lindsay, Alison; Hickman, Deborah; Srinivasan, Mythily; Oral Pathology, Medicine and Radiology, School of DentistryA disproportionate increase in activated nuclear factor-kappa B (NF-κB) has been shown to drive the Aβ deposition, neuroinflammation and neurodegeneration in Alzheimer’s disease (AD). Hence, selective targeting of activated p65 represents an attractive therapeutic approach for AD. Glucocorticoid induced leucine zipper (GILZ) is a NF-κB interactant that binds and sequesters the activated p65 in the cytoplasm. The p65 binding domain of GILZ adopts a polyproline type II helical conformation, a motif that acts as an adaptable glove in the interface with the binding partner and constitutes an excellent template for drug design. Previously, peptide analogs of the p65 binding domain of GILZ, referred to as GA have been shown to suppress pathology in the lipopolysaccharide induced model of neuroinflammation. In this study, we investigated the CNS delivery of labeled GA administered intraperitoneally in adult mice for a period of upto 24 h. Further, we evaluated the suppressive potential of GA in 5xFAD mice, an aggressive model with five genetic mutations closely associated with human AD. Groups of 5xFAD mice administered GA or control peptide intraperitoneally on alternate days for six weeks were evaluated for Aβ deposition, microglia, inflammation and innate immune responses by immunohistochemistry and real time polymerase reaction. GA was observed in proximity with NeuN positive neurons suggesting that the compound crossed the blood brain barrier to reach the brain parenchyma. Further, GA treatment decreased Aβ load, reduced Iba1 + microglia and glial fibrillary acidic protein (GFAP)+ astrocytes, inhibited inflammatory cytokines and suppressed toll like receptor (TLR-2, TLR-4) expressions in 5xFAD mice. ItemPsychometric Characteristics of Oral Pathology Test Items in the Dental Hygiene Curriculum—A Longitudinal Analysis(MDPI, 2021-05-13) Srinivasan, Mythily; Oral Pathology, Medicine and Radiology, School of DentistryAs the landscape of oral healthcare and the delivery of services continue to undergo change, the dental hygienist plays an increasing role in assisting dentists with oral diagnosis and preventive strategies. Hence, the dental hygiene curriculum standards require biomedical science instructions, including general and oral pathology. Student learning and cognitive competencies are often measured using multiple-choice questions (MCQs). The objectives of this study were to perform a longitudinal analysis of test items and to evaluate their relation to the absolute grades of the oral pathology course in the dental hygiene curriculum. A total of 1033 MCQs covering different concepts of oral pathology administered from 2015 through 2019 were analyzed for difficulty and discriminatory indices, and the differences between the years were determined by one-way ANOVA. Test reliability as determined by the average KR-20 value was 0.7 or higher for each exam. The mean difficulty index for all exams was 0.73 +/− 0.05, and that of the discriminatory index was 0.33 +/− 0.05. Wide variations were observed in the discriminatory indices of test items with approximately the same difficulty index, as well as in the grade distribution in each cohort. Furthermore, longitudinal data analyses identified low achieving cohorts amongst the groups evaluated for the same knowledge domain, taught with the same instruction, and using similar test tools. This suggest that comparative analyses of tests could offer feedback not only on student learning attributes, but also potentially on the admission processes to the dental hygiene program. ItemTaste Dysfunction and Long COVID-19(Frontiers, 2021-07-14) Srinivasan, Mythily; Oral Pathology, Medicine and Radiology, School of DentistrySevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent for the coronavirus disease 2019 (COVID-19), has imposed unprecedented morbidity and mortality worldwide. As of June 2021, globally over 163 million individuals are infected and nearly 3.4 million individuals have died. Emerging concerns include complaints of persistent symptoms for extended periods in recovered individuals. Cellular damage due to disease and/or treatment, prolonged viral shedding, chronic immune inflammatory response, and pro-coagulant state induced by SARS-CoV-2 infection are suggested mechanisms contributing to the symptom sequelae. ItemCERE-120 Prevents Irradiation-Induced Hypofunction and Restores Immune Homeostasis in Porcine Salivary Glands(Elsevier, 2020-09-11) Lombaert, Isabelle M. A.; Patel, Vaishali N.; Jones, Christina E.; Villier, Derrick C.; Canada, Ashley E.; Moore, Matthew R.; Berenstein, Elsa; Zheng, Changyu; Goldsmith, Corinne M.; Chorini, John A.; Martin, Daniel; Zourelias, Lee; Trombetta, Mark G.; Edwards, Paul C.; Meyer, Kathleen; Ando, Dale; Passineau, Michael J.; Hoffman, Matthew P.; Oral Pathology, Medicine and Radiology, School of DentistrySalivary gland hypofunction causes significant morbidity and loss of quality of life for head and neck cancer patients treated with radiotherapy. Preventing hypofunction is an unmet therapeutic need. We used an adeno-associated virus serotype 2 (AAV2) vector expressing the human neurotrophic factor neurturin (CERE-120) to treat murine submandibular glands either pre- or post-irradiation (IR). Treatment with CERE-120 pre-IR, not post-IR, prevented hypofunction. RNA sequencing (RNA-seq) analysis showed reduced gene expression associated with fibrosis and the innate and humoral immune responses. We then used a minipig model with CERE-120 treatment pre-IR and also compared outcomes of the contralateral non-IR gland. Analysis of gene expression, morphology, and immunostaining showed reduced IR-related immune responses and improved secretory mechanisms. CERE-120 prevented IR-induced hypofunction and restored immune homeostasis, and there was a coordinated contralateral gland response to either damage or treatment. CERE-120 gene therapy is a potential treatment for head and neck cancer patients to influence communication among neuronal, immune, and epithelial cells to prevent IR-induced salivary hypofunction and restore immune homeostasis.