• Attrition in a cluster randomized controlled trial: Lessons learned from the pilot study in the Educational Program to Increase Colorectal Cancer Screening

      Smith, Selina A.; Delmoor, Ernestine; Sheats, Joyce Q.; Claridy, Mechelle D.; Damus, Francesca; Alema-Mensah, Ernest; Blumenthal, Daniel S.; School of Medicine; Morehouse College; Georgia Regents University (2013)
    • Augusta Training Shop: Snowflakes

      Holsey, Alisia; Smith, Kelsey; Whitaker, Dantavious; Medcalfe, Simon; Hull College of Business (2015-08-10)
      The Augusta Training Shop was founded in 1947 as a daycare, but transformed into a work training facility for adults with mental and physical disabilities. The Training Shop’s main business was furniture restoration which was supported by donations and fundraisers such as derby days. In 2012, the executive director of the Augusta Training Shop, Audrey Murell, designed a fundraising program to aid in supporting the nonprofit. Snowflakes could be made by mentally and physically challenged workers from cane used to restore furniture. In 2013, the first full year of production, the snowflakes generated revenue of close to $25,000. In 2014, while attending a trade show, Audrey was asked if she could provide a bulk purchase discount. This raised several unanswered questions: How big of a discount could be given to wholesalers? The Training Shop was faced with a dilemma if they gave too big of a discount, would the company take a loss on the snowflake fundraiser? Moreover, Audrey was left clueless when it came down to the average cost to produce each snowflake. She knew that the snowflakes could bring in more revenue to help cover some of the higher expenses in the nonprofit, but were they profitable? Audrey had to adapt to an actual business mindset for her to be able to produce the snowflakes. She needed to figure out her direct cost and indirect cost per snowflakes in order to become successful with the snowflake fundraiser. Overall, her long-term goal was to create more jobs, revenue, and to spread the gift of the snowflakes among other nonprofits.
    • Authenticity and Performativity in Saul Bellow’s Herzog

      Quiller, Walter; Katherine Reese Pamplin College of Arts, Humanities, and Social Sciences; Hoffman, Todd (2015-03-27)
      Saul Bellow's Herzog provides a platform through which the concept of subjectivity can be discussed. For some theorists, the subject is something that can be grounded. Martin Heidegger for instance employs ontology in order to present a stable, authentic subjectivity. In contrast, Judith Butler argues that this subject does not exist. Rather it is an illusion carried out through performances. Research on Heidegger's idea of authenticity and Butler's notion of performativity provides insight into Bellow's treatment of subjectivity. The characters in Herzog both reject and fail to uphold Heideggerian standards of authenticity. However they do participate in performativity. The identities that they attempt to convey are actually performances that create illusions of a grounded subject. Through analyses of Bellow's central characters, it is evident that he rejects the Heideggerian view and that the Butlerian model of subjectivity (or anti-subjectivity) is a more appropriate means of exploring subjectivity in the novel. Therefore viewing literary characters as performers (in the Butlerian sense) reveals Bellow’s tendency to present characters who do not have stable identities, but instead fluid illusions of identity.
    • The Autoimmune Regulator (Aire) Confers Immunosuppressive Properties to Dendritic Cells

      Eisenman, Daniel; Center for Biotechnology and Genomic Medicine (2007-05)
      The Autoimmune regulator (Aire) is a transcription factor that controls expression of self antigens by thymic epithelium and it plays a critical role in the deletion of autoreactive thymocytes and prevention of autoimmunity. Recent studies have reported Aire expression in dendritic cells (DC) located in spleen and lymph nodes, suggesting a role for Aire in extra-thymic tolerance induction. Molecular and functional studies conducted in this dissertation revealed that Aire induction in bone marrow derived DC results in expression of immunosuppressive cytokines and decreased expression of co-stimulatory molecules. Similar results were also obtained from lenti-virus-mediated Aire overexpression in the DC2.4 dendritic cell line. It was further shown that DC from Aire'7' mice exhibited greater antigen presenting function both in vitro and in vivo. These DC were more potent stimulators of T cell proliferation leading to increased IL-2 and IFNy production. These studies suggest that Aire7' DC may play a role in exacerbating the autoimmunity seen in Aire7' mice. DC over-expressing Aire were shown to suppress activation and proliferation of naive T cells and promote activation-induced cell death of activated T cells. Furthermore, we demonstrate that Aire also controls transcription of tissue-specific antigens in DC. These results, together, suggest that Aire plays an important role in the tolerogenic function of DC.
    • B-Lymphoid Cells with Attributes of Dendritic Cells Regulate T Cells via Indoleamine 2,3 Dioxygenase

      Johnson, Burles Avner III; Cancer Research Center (2012-04)
      A rare subset of murine dendritic cells expressing the B cell marker CD19 are specialized to express the T cell regulatory enzyme indoleamine 2,3 dioxygenase (IDO-competent DCs). Here we show that IDO-competent DCs expressed Pax5, a transcription factor that maintains B cell lineage commitment, and drives expression of CD19 and surface immunoglobulin (slg). However IDO-competent DCs also exhibited multiple attributes of DCs including DC marker expression and potent T cell stimulatory properties when IDO was not induced. Unexpectedly, DCs expressing IDO were present in B cell deficient mice following TLR9 ligation, indication that B cell receptor (BCR) expression was not required for IDO function. Conversely, DCs from CD19 deficient mice did not express IDO after in vivo TLR9 ligation. This defect was not caused by blockade of IDO-competent DC development in CD19-deficient mice because IDO expression was incduced in these cells by in vitro interferon gamma treatment. Even though DCs from B cell deficient mice expressed IDO following TLR9 ligation, regulatory T cells (Tregs) from B cell deficient mice had impaired suppressor activity. IDO-competent DCs expressed high levels of CD1d-deficient mice. IDO-competent DCs also expressed IL-10 deficient mice to express IDO. Finally we demonstrated that DCs from draining lymph nodes (dLNs) of four week old prediabetic female non obese diabetic (NOD) mice expressed functional IDO following topical treatment with phorbol myristate acetate (PMA). However DCs from dLNs of six week old prediabetic NOD female mice did not express IDO following topical PMA treatment, indicating a critical defect in a specific immunosuppressive mechanism in NOD female mice that coincides with the appearance of insulitis. These data identify IDO competent DCs as a unique B lymphoid lineage cell type that has tightly controlled regulatory properties, and a DC subset whose acquired defect may contribute to autoimmune disease in NOD mice.
    • Balanced Dopamine Is Critical for Pattern Completion during Associative Memory Recall

      Li, Fei; Wang, Lei Phillip; Shen, Xiaoming; Tsien, Joe Z.; Brain & Behavior Discovery Institute (2010-10-27)
      Pattern completion, the ability to retrieve complete memories initiated by partial cues, is a critical feature of the memory process. However, little is known regarding the molecular and cellular mechanisms underlying this process. To study the role of dopamine in memory recall, we have analyzed dopamine transporter heterozygous knockout mice (DAT+/-), and found that while these mice possess normal learning, consolidation, and memory recall under full cue conditions, they exhibit specific deficits in pattern completion under partial cue condition. This form of memory recall deficit in the dopamine transporter heterozygous knockout mice can be reversed by a low dose of the dopamine antagonist haloperidol, further confirming that the inability to retrieve memory patterns is a result of dopamine imbalance. Therefore, our results reveal that a delicate control of the brain's dopamine level is critical for pattern completion during associative memory recall.
    • Baseline measures of importance, confidence, and current practice in an SBIRT training program: the role of experience for advanced practice RNs

      Johnson, J. Aaron; Savage, Christine L.; Finnell, Deborah S.; Seale, J. Paul; Georgia Regents University; Johns Hopkins University; Mercer University School of Medicine (2015-05)
    • BDNF-induced recruitment of TrkB receptor into neuronal lipid rafts

      Suzuki, Shingo; Numakawa, Tadahiro; Shimazu, Kazuhiro; Koshimizu, Hisatsugu; Hara, Tomoko; Hatanaka, Hiroshi; Mei, Lin; Lu, Bai; Kojima, Masami; Institute of Molecular Medicine and Genetics (2004-12-20)
      Brain-derived neurotrophic factor (BDNF) plays an important role in synaptic plasticity but the underlying signaling mechanisms remain unknown. Here, we show that BDNF rapidly recruits full-length TrkB (TrkB-FL) receptor into cholesterol-rich lipid rafts from nonraft regions of neuronal plasma membranes. Translocation of TrkB-FL was blocked by Trk inhibitors, suggesting a role of TrkB tyrosine kinase in the translocation. Disruption of lipid rafts by depleting cholesterol from cell surface blocked the ligand-induced translocation. Moreover, disruption of lipid rafts prevented potentiating effects of BDNF on transmitter release in cultured neurons and synaptic response to tetanus in hippocampal slices. In contrast, lipid rafts are not required for BDNF regulation of neuronal survival. Thus, ligand-induced TrkB translocation into lipid rafts may represent a signaling mechanism selective for synaptic modulation by BDNF in the central nervous system.
    • Behavioral Defects in Chaperone-Deficient Alzheimer's Disease Model Mice

      Ojha, Juhi; Karmegam, Rajalakshmi V.; Masilamoni, J. Gunasingh; Terry, Alvin V.; Cashikar, Anil G.; Center for Molecular Chaperone/Radiobiology & Cancer Virology; Department of Pharmacology and Toxicology (2011-02-17)
      Molecular chaperones protect cells from the deleterious effects of protein misfolding and aggregation. Neurotoxicity of amyloid-beta (Ab) aggregates and their deposition in senile plaques are hallmarks of Alzheimer's disease (AD). We observed that the overall content of aB-crystallin, a small heat shock protein molecular chaperone, decreased in AD model mice in an age-dependent manner. We hypothesized that aB-crystallin protects cells against Ab toxicity. To test this, we crossed aB-crystallin/HspB2 deficient (CRYAB-/-HSPB2-/-) mice with AD model transgenic mice expressing mutant human amyloid precursor protein. Transgenic and non-transgenic mice in chaperone-sufficient or deficient backgrounds were examined for representative behavioral paradigms for locomotion and memory network functions: (i) spatial orientation and locomotion was monitored by open field test; (ii) sequential organization and associative learning was monitored by fear conditioning; and (iii) evoked behavioral response was tested by hot plate method. Interestingly, aB-crystallin/HspB2 deficient transgenic mice were severely impaired in locomotion compared to each genetic model separately. Our results highlight a synergistic effect of combining chaperone deficiency in a transgenic mouse model for AD underscoring an important role for chaperones in protein misfolding diseases.
    • Beliefs and Behaviors about Breast Cancer Recurrence Risk Reduction among African American Breast Cancer Survivors

      Smith, Selina A.; Whitehead, Mary S.; Yoo, Wonsuk; Ansa, Benjamin E.; Coughlin, Steven S.; Augusta University (2015)
    • Beyond Genome-Wide Association Studies: New Strategies for Identifying Genetic Determinants of Hypertension

      Wang, Xiaoling; Prins, Bram P.; Sõber, Siim; Laan, Maris; Snieder, Harold; Georgia Institute for Prevention of Human Diseases and Accidents; Department of Pediatrics (2011-12-28)
      Keywords: Linkage analysis
    • Beyond the H&P: Writing Clinical Notes as a Junior Medical Student

      Everett, Ross G.; Brown, Shilpa P.; Medical College of Georgia (2016-03)
      The assessment and evaluation of written communication is included within the sex competencies established by the Accreditation Council for Graduate Medical Education.1 Additionally, these skills are widely represented in American medical curricula.1 Still, few studies have identified the types of written documentation that are evaluated or how these are assessed.2 There is relatively little published literature regarding the challenges that writing patient care notes as a junior medical student present. However, numerous posts and inquiries on web-based resources for medical students indicate that many students struggle with patient care notes as they begin their clerkships. Additionally, the large volume of resources made available on the websites of individual medical institutions may support the notion that these challenges persist year after year for some time now. [Introduction]
    • Big Data Clincial Research: Validity, Ethics, and Regulation

      Balas, E. Andrew; Sexton, Joanne; Georgia Regents University (2015)
      Electronic Health Records (EHR) promise improvement for patient care and also offer great value for biomedical research including clinical, public health, and health services research. Unfortunately, the full potential of EHR big data research has remained largely unrealized. The purpose of this study was to identify rate limiting factors, and develop recommendations to better balance unrestricted extramural EHR access with legitimate safeguarding of EHR data in retrospective research. By exploring primary, secondary, and tertiary sources, this review identifies external constraints and provides a comparative analysis of social influencers in retrospective EHR-based research. Results indicate that EHRs have the advantage of reflecting the reality of patient care but also show a frequency of between 4.3-86% of incomplete and inaccurate data in various fields. The rapid spread of alternative analytics for health data challenges traditional interpretations of confidentiality protections. A confusing multiplicity of controls creates barriers to big data EHR research. More research on the use of EHR big data is likely to improve accuracy and validity. Information governance and research approval processes should be simplified. Comprehensive regulatory policies that do not exclusively cover health care entities, are needed. Finally, new computing safeguards are needed to address public concerns, like research access only to aggregate data and not to individually identifiable information.
    • Breathing New Life into an Old Curriculum: Ideas for Curriculum Improvement in the First Month of Clinical Training; What Does the Search Process Look Like?

      Boyer, Tanna; Braun, Kelli; Chhatbar, Pankaj; Kumar, Viakas; Steine, Martin; Arthur, Mary E.; Anesthesiology and Perioperative Medicine & Obstetrics and Gynecology (2016-03)
      Our goal was to develop an innovative, engaging, one-month curriculum that could be implemented at a low cost using existing validated resources.
    • Cardiometabolic Biomarkers in Young Black Girls: Relations to Body Fatness and Aerobic Fitness, and Effects of a Randomized Physical Activity Trial

      Gutin, Bernard; Harris, Ryan A.; Howe, Cheryl A.; Johnson, Maribeth H.; Zhu, Haidong; Dong, Yanbin; Georgia Institute for Prevention of Human Diseases and Accidents; Department of Pediatrics; Department of Biostatistics and Epidemiology (2011-10-11)
      There is little evidence from randomized trials showing that physical activity alone influences biomarker profiles in youths. This study tested two hypotheses: (i) that elevated body fatness and poor fitness would be associated with unfavorable levels of cardiometabolic biomarkers in 8- 12-y-old black girls (n = 242) and (ii) that a 10-mo PA intervention would have favorable effects on the fatness-related cardiometabolic biomarkers. At baseline, all fatness indices (i.e., percent body fat, visceral adipose tissue, BMI, and waist circumference) were significantly (P < 0.05) associated with unfavorable levels of insulin, glucose, systolic BP, diastolic BP, triglycerides, C-reactive protein (CRP), and fibrinogen. Aerobic fitness was significantly (P < 0.05) associated with favorable levels of insulin, CRP, fibrinogen, and HDL2. The PA intervention had significant and favorable effects on fitness, fatness, and two biomarkersâ resting heart rate and LDL cholesterol. More research is needed to clarify what types of interventions can enhance the cardiometabolic health of youths.
    • Cell drinking: a closer look at how macropinocytosis drives cholesterol uptake in atherosclerotic vessels

      Lin, Huiping; Vascular Biology Center (Augusta University, 2020-05)
      Atherosclerotic vascular disease is the underlying cause of myocardial infarction, stable and unstable angina, stroke, peripheral artery disease and sudden cardiac death. Collectively, these cardiovascular diseases are responsible for the majority of deaths worldwide. Internalization of modified apolipoprotein B–containing lipoproteins by macrophages through scavenger receptor (SR)-mediated pathways is generally viewed as an essential step for the initiation and progression of atherosclerosis. Our studies were designed to investigate the contribution of receptor-independent LDL macropinocytosis to arterial lipid accumulation and atherosclerosis. We developed novel genetic and pharmacological approaches, utilized high resolution imaging techniques and employed unique in vivo lipid quantification assays to investigate the role of macrophage macropinocytosis in the pathogenesis of atherosclerosis. My results demonstrate that the macropinocytosis inhibitor EIPA and selective deletion of a key pathway regulating macropinocytosis in myeloid cells substantially decreased lesion size in both hypercholesterolemic wild type (WT) and SR knockout (CD36-/-/SR-A-/-) mice. Stimulation of macropinocytosis using genetic and physiologically relevant approaches promotes lipoprotein internalization by WT and CD36-/-/SR-A-/- macrophages, leading to foam cell formation. Serial section high-resolution imaging of murine and human atherosclerotic arteries identified for the first time subendothelial macrophages for the first time that demonstrate plasma membrane ruffling, cupping and macropinosome internalization. Immunoelectron microscopy, 3D reconstruction of macrophage foam cells and in vivo LDL tracking demonstrate macrophage internalization of LDL in human and murine atherosclerotic arteries via macropinocytosis. We next performed a large, unbiased-screen of an FDA-approved drug library to identify clinically relevant therapeutic agents that can be repurposed as pharmacological inhibitors of macropinocytosis. Our studies identified a low MW compound (imipramine) that inhibits macrophage macropinocytosis in vitro and in vivo. Imaging, toxicity and selectivity studies demonstrated that imipramine is a potent (IC50 = 130.9 nM), non-toxic (selectivity index CC50/IC50 > 300) and selective inhibitor of macropinocytosis. Repurposing of imipramine to inhibit macropinocytosis in hypercholesterolemic mice substantially decreased plaque development compared with control treatment. Taken together, our findings challenge the SR paradigm of atherosclerosis and identify inhibition of receptor-independent macrophage macropinocytosis as a new therapeutic strategy that may be beneficial in the treatment of atherosclerosis and its cardiovascular consequences.
    • Cellular and Molecular Players in Neuromuscular Junction (NMJ) Formation and Function

      Barik, Arnab; Institute of Molecular Medicine and Genetics (2014-04)
      There are three distinct segments in this dissertation. First, I attempted to address the role of Schwann cells in mammalian neuromuscular junction (NMJ) development and function. Schwann cells at the NMJs do not form myelin sheaths and are known as terminal Schwann cells. Terminal Schwann cells are thought to be analogous to astrocytes in the central nervous system. Schwann cells (as described in details in the next section) provide trophic support to motor axons and modulate synaptic activity by sensing neurotransmitter release at the nerve terminal. However, the role of Schwann cells in synapse formation and maintenance remains unknown. Second, during NMJ formation, anterograde signals from nerve to muscle, and retrograde signals from muscle to nerve are critical for the establishment of a functional synapse. Research over the last three decades has contributed to our understanding of the role of the anterograde signaling at NMJ. However, identification of muscle-derived retrograde signals involved in motoneuron terminal differentiation remains scarce. Recent work from our laboratory suggests that genes that are transcriptionally regulated by p-catenin in muscles might play a crucial role in pre-synaptic differentiation at the NMJ.2 Third, Agrin-LRP4-MuSK signaling is critical for NMJ formation. At the NMJ, LRP4-mediated activation of MuSK by neural Agrin is required for post-synaptic differentiation. Mice that lack any one of the three genes fail to form NMJs and die at birth. Due to perinatal lethality of these null mice, less is known about how Agrin-LRP4-MuSK might regulate NMJ maintenance. Moreover, mutations in Agrin, LRP4, and MuSK have been reported in patients diagnosed with congenital myasthenic syndrome (CMS), and autoantibodies against MuSK and LRP4 have been detected in patients with myasthenia gravis (MG). However, the role of Agrin-LRP4-MuSK in the etiology of these neuromuscular disorders is not clear.
    • Ceramide in Stem Cell Differentiation and Embryo Development: Novel Functions of a Topological Cell-Signaling Lipid and the Concept of Ceramide Compartments

      Bieberich, Erhard; Institute of Molecular Medicine and Genetics (2010-12-29)
      In the last two decades, the view on the function of ceramide as a sole metabolic precursor for other sphingolipids has completely changed. A plethora of studies has shown that ceramide is an important lipid cell-signaling factor regulating apoptosis in a variety of cell types. With the advent of new stem cell technologies and knockout mice for specific steps in ceramide biosynthesis, this view is about to change again. Recent studies suggest that ceramide is a critical cell-signaling factor for stem cell differentiation and cell polarity, two processes at the core of embryo development. This paper discusses studies on ceramide using in vitro differentiated stem cells, embryo cultures, and knockout mice with the goal of linking specific developmental stages to exciting and novel functions of this lipid. Particular attention is devoted to the concept of ceramide as a topological cell-signaling lipid: a lipid that forms distinct structures (membrane domains and vesicles termed â sphingosomeâ ), which confines ceramide-induced cell signaling pathways to localized and even polarized compartments.