• Polyfunctional CD4+ T cells synergize with chemotherapy to reprogram tumor metabolism towards a curative outcome

      Habtetsion, Tsadik Ghebreamlak; Department of Biochemistry and Molecular Biology (8/3/2017)
      CD4+ T cells are critical mediators of anti-tumor immunity. Accumulating evidence from preclinical and clinical studies suggests that tumor-reactive CD4+ T cells in adoptive T cell therapy (ACT) have the potential to effectively control tumor growth. In most ACT clinical settings, chemotherapeutic agents are used to induce an immunostimulatory milieu which facilitates the effector function of donor T cells. Although the efficacy of ACT has been well-established, currently only a fraction of patients with certain types of malignancy have benefited, highlighting the need for improved ACT strategies. Recent studies have revealed that the metabolic reprogramming by cancer cells attenuate antitumor immune response by imposing nutrient restrictions in the tumor microenvironment, which leads to defective T cell responses. In the current study, we set out to explore how Cyclophosphamide (CTX) and tumor reactive CD4+ T cells alter the metabolic features of cancer cells. By comparing the global metabolic profiling of tumors pre and post-treatment, we found that CXT+CD4 ACT elicited a metabolic catastrophe affecting multiple pathways critical for cancer progression. Particularly, CTX+CD4 ACT led to marked reduction in glutathione (GSH) levels, increased accumulation of reactive oxygen species (ROS) and oxidative DNA damage product in tumors. Importantly, administration of N-acetyl-L-cysteine diminished the curative effect of CTX+CD4 ACT. Moreover, pharmacological inhibition of GSH using Buthionine Sulfoximine (BSO) following CTX significantly delayed tumor growth in mice. Mechanistically, we found that TNFα synergized with chemotherapy to reduce intracellular GSH levels and promote ROS induction. TNFα enhanced cell death in chemotherapy pre-treated tumor cells and the cytotoxic effect was reversed by adding GSH exogenously. Importantly, the curative effect of CTX+CD4 ACT was abrogated after TNFα neutralization. Additionally, we found that CTX+CD4 ACT led to tumor vascular disruption causing hemorrhagic necrosis of tumors. IFNγR-deficient mice failed to reject tumor after CTX+CD4 ACT and had intact tumor vasculature. Collectively, our data reveal that tumor reactive CD4+T cells disrupt the redox homeostasis of cancer cells in TNFα-dependent manner. Whereas CD4+T cells derived IFNγ targeted tumor endothelial cells to cause vascular disruption and tissue ischemia. The combined action of these two cytokines leads to eventual eradication of established tumor.
    • Polymeric-calcium phosphate cement composites-material properties: in vitro and in vivo investigations.

      Khashaba, Rania M.; Moussa, Mervet M; Mettenburg, Donald J; Rueggeberg, Frederick A.; Chutkan, Norman B.; Borke, James L.; Department Oral Biology; Department Orthopedic Surgery; Department of Oral Rehabilitation (2010-09-02)
      New polymeric calcium phosphate cement composites (CPCs) were developed. Cement powder consisting of 60 wt% tetracalcium phosphate, 30 wt% dicalcium phosphate dihydrate, and 10 wt% tricalcium phosphate was combined with either 35% w/w poly methyl vinyl ether maleic acid or polyacrylic acid to obtain CPC-1 and CPC-2. The setting time and compressive and diametral tensile strength of the CPCs were evaluated and compared with that of a commercial hydroxyapatite cement. In vitro cytotoxicity and in vivo biocompatibility of the two CPCs and hydroxyapatite cement were assessed. The setting time of the cements was 5-15 min. CPC-1 and CPC-2 showed significantly higher compressive and diametral strength values compared to hydroxyapatite cement. CPC-1 and CPC-2 were equivalent to Teflon controls after 1 week. CPC-1, CPC-2, and hydroxyapatite cement elicited a moderate to intense inflammatory reaction at 7 days which decreased over time. CPC-1 and CPC-2 show promise for orthopedic applications.
    • Porphyromonas gingivalis Escape-from Autophagy in Human Myeloid Dendritic Cells via Minor Mfa-1 Fimbra-DC-Sign Interactions

      El-Awady, Ahmed; Department of Oral Biology (2014-03)
      In professional phagocytes, early receptor recognition is crucial to determine the fate of engulfed microorganisms. Among the many pattern recognition receptors (PRRs) expressed by dendritic cells (DCs), the C-type lectin DC-SIGN is of particular interest as it has been associated with immunosuppression by infecting pathogens. While autophagy has emerged as a major immune mechanism against microbes, very little is presently understood about its role in elimination o f intracellular pathogens; especially in the context o f the PRR diversity expressed by DCs. Hence, the study aimed to investigate the role of DC-SIGN targeting by the anaerobic pathogen Porphyromonas gingivalis in its intracellular survival within myeloid DCs and how intracellular routing through early and late endosomes, autophagosomes and lysosomes relate to this survival. Employed in this investigation were human monocyte derived DCs and a panel of isogenic fimbriae deficient mutant strains of P. gingivalis that express the DC-SIGN ligand (Mfa-1 fimbriae) and/or the TLR2 ligand (FimA fimbriae). The results show that uptake of P. gingivalis by the nonDC-SIGN dependent route resulted in intracellular killing and elimination of intracellular content of P. gingivalis. This route was associated with early endosomal routing through Rab5, increased LC3-II and LAMP-1, as well as the formation of double membrane intracellular phagophores. In contrast, DC-SIGN dependent uptake did not induce significant levels of Rab5, LC3- II, and LAMP1. Moreover, P. gingivalis was mostly contained within single membrane vesicles where it survived intracellularly. Survival was ameliorated by forced autophagy. These results suggest that myeloid DCs are fully capable of eliminating intracellular pathogens by autophagy but that selective engagement of DC-SIGN is a microbial tactic for evasion of antibacterial autophagy leading to intracellular survival.
    • Portrayal of Mental Illness in Edgar Allan Poe’s “The Tell-Tale Heart”

      Shaikh, Arika; English and Foreign Languages (Augusta University Libraries, 2020-05-04)
      This item presents the abstract for a poster presentation at the 21st Annual Phi Kappa Phi Student Research and Fine Arts Conference.
    • Post Traumatic Stress Disorder: Insights from Cat Hair and Catfish

      Nalloor, Rebecca Ipe; Department of Pharmacology and Toxicology (2012-06)
      Post traumatic stress disorder (PTSD) is an anxiety disorder that develops in some, but not all, individuals following a traumatic experience. Established PTSD is difficult to treat, therefore prevention and early intervention is important to reduce prevalence. Identifying individuals susceptible to developing PTSD before trauma exposure and investigating neurophysiological processes that contribute to the disease will help develop better treatment and preventive methods. Limitations to such investigations in humans make animal models a necessary tool. Like humans, only some rats develop PTSD-like behavior after trauma but pre-trauma identification of these rats was not possible until now. We were able to reliably predict before trauma exposure which rats are susceptible (Susceptible) or resistant (Resistant) to developing two PTSD-like symptoms: impaired fear extinction and lasting elevation in acoustic startle responses. We hypothesized that Susceptible rats will have pre-existing alterations in plasticity-related responses in the hippocampus, a brain region whose altered size and function is associated with PTSD diagnosis. We also hypothesized that Susceptible rats will differ from Resistant rats in the acquisition of a traumatic event and tested this using Arc/H1a catFISH, a cellular imaging technique that detects neurons expressing plasticity-related immediate early genes (IEGs) during behavior. We found that, in Resistant rats a large proportion of the same dorsal CA1 (dCA1) neurons expressed IEGs during two identical explorations of the experimental box. This suggests that dCA1 responds to identical events with high fidelity. In Susceptible rats, however, different neuronal ensembles expressed IEGs during identical explorations suggesting a lack of fidelity in hippocampal response to identical events. In addition fewer ventral CA3 neurons expressed IEGs during the second exploration in Susceptible as compared to Resistant rats. We also examined the basolateral nucleus of the amygdala, but found no difference in IEG expression. Contrary to hypothesis, differences between Susceptible and Resistant rats during a foot shock paired exploration (traumatic event) were not pronounced. These findings show that rats susceptible to developing PTSD-like symptoms can be behaviorally identified and have altered hippocampal plasticity-related responses prior to the trauma. This study provides a frame-work for the investigation and remediation of susceptibilities.
    • Post-Implant Placement Cervical Burnout

      Faigen, Alexander; Stevens, Mark R.; James, Jeffrey N.; Oral Surgery (2020-02)
      To evaluate and compare post implant placement cervical bone loss within the Dental College of Georgia and among its dental specialties. This information will allow us to identify patient's at risk for bone loss therefore improving patient satisfaction and overall success of the implant.

      Faigen, A; James, J; Stevens, M; Department of Oral and Maxillofacial Surgery (Augusta University, 2019)
      Lifetime implant success, in both esthetic and functional categories is a multifactorial process. Connective tissues, hard and soft, play a major role in the health of an implant platform and its associated restoration. While bone loss around the crestal portion of the implant up to 2.0mm within the first year of use is expected. We desire to determine factors which predict bone loss and overall implant success.. Many of the factors which can be used to account for such bone loss are inappropriate stresses and force distribution, trauma during surgery, micromechanical movement, infection, and multiple other patient factors. Bone loss has not been linked to a single implant type, placement procedure, or specialty, but remains a significant challenge in the long-term success of implants.
    • Postmodernism & the Sexual Awakening of E.L. Doctorow's Ragtime

      Rosier, Melanie (2017-03-06)
      This analysis utilizes both a Postmodernist and Feminist approach to E.L. Doctorow's novel Ragtime in order to provide a social commentary on the hardships of women and minorities in Pre-WWI America. Historically, the patriarchal system has contributed to the sociopolitical oppression of women on an international level. The sexual repression of women, in particular, has lead to a system of hierarchy that has been permanently instilled in society. However, with the turn of the nineteenth century, the dissolution of familial roles for women began taking place. In this analysis, Doctorow's narration of the lives of five different female characters is defined as an illumination of the socioeconomic hardships of women in the height of immigration and labor exploitation within the United States. This historiographical commentary continues by recognizing the inability to acquire liberation from oppression for minority women.
    • The potential role of indoleamine 2,3 dioxygenase (IDO) as a predictive and therapeutic target for diabetes treatment: a mythical truth

      Baban, Babak; Penberthy, W. Todd; Mozaffari, Mahmood S.; Department of Oral Biology (2010-03-19)
      Keywords: Individual tolerance
    • Power, Creativity and Reminiscence in the Elderly

      Bramlett, Martha H.; Department of Physiological and Technological Nursing; American Nurses' Foundation (1990-05)
      The primary purpose of this study was to investigate the relationship between creativity and power in a sample of well elderly adults. Additionally, the usefulness of reminiscent storytelling as a therapeutic modality in patterning power and creativity in well elders was explored. The study was conceptualized within Rogers' (1986) Science of Unitary Human Beings, and incorporated Barrett's theory of power, the latter derived from the Rogerian conceptual system. Specifically, the study sought evidence for the mutual patterning of power and creativity in older adults.
    • Predicting Screw Channel Location in Definitive Fixed Detachable Zirconia Prostheses

      Oketade, Sadiq; Torosian, Aram; Kang, Juan; Londono, Jimmy; Restorative Sciences (2020-02)
      The purpose of this presentation is to show a simple way to use 3 Shape Dental Design software to accurately anticipate screw channel location when fabricating definitive Fixed Detachable Zirconia Prostheses.

      Lewis, Casey; Department of Psychological Sciences (Augusta University, 2019-12)
      Success in counseling psychology programs includes both academic and clinical performance. Graduate Record Examinations (GRE) and undergraduate grade point average (UGPA) have been linked to the academic aspects of success in programs (e.g., Daehnert & Carter, 1987). Letters of recommendation, personal statements, and interviews are thought to assess interpersonal functioning, which is important in therapeutic ability (e.g., Barnicot, Wampold, & Priebe, 2014). However, these assessments have significant limitations. The current study uses standardized personality assessments in conjunction with GRE and UGPA to predict student success. The Empathic Concern subscale of the Interpersonal Reactivity Index (IRI; Davis, 1980, 1983) was used to assess self-reported empathy. Additionally, a performance-based measure, the Social Cognition and Object Relations Scale – Global Rating Method (SCORS-G; Westen, 1995) was used to rate Thematic Apperception Test (TAT; Murray, 1973) narratives to assess trainees’ interpersonal functioning. Variables related to students’ completion vs. non-completion of the first year of a master in clinical and counseling psychology program were analyzed using t-tests and discriminant function analyses. Our findings suggest that a performance-based measure of interpersonal ability is useful at assessing applicants to counseling psychology programs, while GRE scores may not be as useful in the admissions process. Additionally, a significantly higher rate of male vs. female non-completers may reveal a trend in clinical/counseling psychology programs that needs to be addressed.
    • Predicting Violence Risk and Recidivism in Female Parolees: A State-Wide Sample

      Britt, Jessica Y.; Patton, Christina L.; Remaker, Dominique N.; Vitacco, Michael J.; Prell, Lettie; Department of Psychiatry (2020-07-20)
    • Prediction of diabetic retinopathy: role of oxidative stress and relevance of apoptotic biomarkers

      Al-Shabrawey, Mohamed; Smith, Sylvia B; Department of Oral Biology; Department of Ophthalmology; Vision Discovery Institute; Department of Cellular Biology and Anatomy (2010-03-23)
      Keywords: Diabetic retinopathy
    • Predictive Inference for Linear and Circular Concomitants with Biomedical Applications

      Howie, Melissa; Department of Philosophy (Augusta University, 2021-07)
      Let (X_i, Y_i), for i=1,...,n, be a random sample from a bivariate distribution. If the sample is ordered with respect to one of the variables, say X, then the rth ordered X-value is called the rth order statistic and is denoted X_{r:n}. The Y-value corresponding to this value is called the concomitant of the rth order statistic and is denoted Y_{[r:n]}. In biomedical research, there is an interest in predicting the concomitant variable corresponding to the rth order statistic of the other variable. For example, one may be interested in predicting the time at which a patient has the peak blood pressure or the mercury level in fish where the water is most polluted. One such distribution of interest is the bivariate exponential conditionals distribution (BEC), whose conditional distributions are both exponential. The asymptotic predictive distribution of the concomitants of order statistics from the BEC is derived. The results are used in a prediction problem involving the mercury concentration in largemouth bass sampled from Florida lakes, as a function of surface water pollution level. Clinicians are often confronted with data such that one variable is linear and the other variable is circular, i.e., measured as an angle. A particular linear-circular distribution of interest is the exponential circular normal distribution. The predictive distribution of concomitants of order statistics from the exponential circular normal distribution is derived. The results are applied to predicting the future value of time at maximum heart rate in subjects from the Augusta Heart Study, a longitudinal study of normotensive children with verified family histories of cardiovascular diseases (e.g., hypertension and premature myocardial infarction).
    • Prehistoric Dinosaurs: An Exploration of Fact vs. Fiction Through the Creation of Comparative Sculptural Forms

      Havens, Krista; Department of Art and Design (Augusta University, 2019-12)
      Prehistoric Dinosaurs: An Exploration of Fact vs. Fiction Through the Creation of Comparative Sculptural Forms, is an art exhibition which displays the differences between how dinosaurs look in film and media verses how they are proposed to have looked based on scientific findings. The impetus for this project was to create a kid friendly educational tool, comprised of three hand-sculpted dinosaurs and three resin cast dinosaurs. The species of dinosaurs created were Carnotaurus, Velociraptor, and Dilophosaurus, some of the most commonly portrayed dinosaurs in the film industry. Each scientifically accurate dinosaur sculpture will be placed next to its film and media representation counterpart to allow for the viewer to compare and contrast the differences in the physical appearances.
    • Preoperative Evaluation with fMRI of Patients with Intracranial Gliomas

      Kapsalakis, Ioannis Z.; Kapsalaki, Eftychia Z.; Gotsis, Efstathios D.; Verganelakis, Dimitrios; Toulas, Panagiotis; Hadjigeorgiou, Georgios; Chung, Indug; Fezoulidis, Ioannis; Papadimitriou, Alexandros; Robinson, Joe Sam; et al. (2012--2012)
    • Preparation, Physical-Chemical Characterization, and Cytocompatibility of Polymeric Calcium Phosphate Cements

      Khashaba, Rania M.; Moussa, Mervet M; Koch, Christopher; Jurgensen, Arthur R.; Missimer, David M.; Rutherford, Ronny L.; Chutkan, Norman B.; Borke, James L.; Department of Oral Biology; Department of Surgery (2011-09-20)
    • Prevalence of Holistic Admission Criteria Among Entry-Level Occupational Therapy Programs

      Taylor, Kristian; Nguyen, Cat-Tien; Grant, Jenny; Brewster, Mary Beth; Barrett, Mary Alice; Benevides, Teal; Cosper, Sharon M.; Department of Occupational Therapy (Augusta University, 2021-09)
      Objectives of Presentation: At the conclusion of this poster, attendees will: 1. Describe the difference between holistic admissions and academic metric- only procedures implemented by entry-level occupational therapy programs. 2. Discuss the relationship between implementation of holistic admissions criteria and entry-level occupational therapy program ranking. Research Purpose: The purpose of this study is to compare the holistic admissions criteria used by the top fifty ranked entry-level occupational therapy master’s and doctoral programs to the fifty lowest ranked programs.
    • The prevalence of intragenic deletions in patients with idiopathic hypogonadotropic hypogonadism and Kallmann syndrome.

      Pedersen-White, Jennifer R; Chorich, Lynn P; Bick, David P; Sherins, Richard J; Layman, Lawrence C; Department of Medicine; Department of Obstetrics and Gynecology; Department of Obstetrics and Gynecology; Institute of Molecular Medicine and Genetics; Institute of Neuroscience (2008-06-23)
      Idiopathic hypogonadotropic hypogonadism (IHH) and Kallmann syndrome (KS) are clinically and genetically heterogeneous disorders caused by a deficiency of gonadotrophin-releasing hormone (GnRH). Mutations in three genes--KAL1, GNRHR and FGFR1--account for 15-20% of all causes of IHH/KS. Nearly all mutations are point mutations identified by traditional PCR-based DNA sequencing. The relatively new method of multiplex ligation-dependent probe amplification (MLPA) has been successful for detecting intragenic deletions in other genetic diseases. We hypothesized that MLPA would detect intragenic deletions in approximately 15-20% of our cohort of IHH/KS patients. Fifty-four IHH/KS patients were studied for KAL1 deletions and 100 were studied for an autosomal panel of FGFR1, GNRH1, GNRHR, GPR54 and NELF gene deletions. Of all male and female subjects screened, 4/54 (7.4%) had KAL1 deletions. If only anosmic males were considered, 4/33 (12.1%) had KAL1 deletions. No deletions were identified in any of the autosomal genes in 100 IHH/KS patients. We believe this to be the first study to use MLPA to identify intragenic deletions in IHH/KS patients. Our results indicate approximately 12% of KS males have KAL1 deletions, but intragenic deletions of the FGFR1, GNRH1, GNRHR, GPR54 and NELF genes are uncommon in IHH/KS.