Medical Univer sity of South Carolina Department of Medicine Research Day 2 0 1 2 R e s e a r c h D ay DEPARTMENT OF MEDICINE RESEARCH DAY JANUARY 19, 2012 Many thanks to the judges who contributed their time and effort to make the 6th annual Department of Medicine Research Day a successful event. Richard Silver, M.D. Alexander Awgulewitsch, Ph.D. P. Darwin Bell, Ph.D. Galina Bogatkevich, M.D., Ph.D Ruth Campbell, M.D., M.S. Luciano J. Costa, M.D., Ph.D. Valerie Durkalski, Ph.D. Hesham El-Shewy, Ph.D. Valerian L.C. Fernandes, M.B.B.S. Patrick Flume, M.D. Robert Gemmill, Ph.D. Gary Gilkeson, M.D. Monika Gooz, M.D., Ph.D. Yan Huang, M.D., Ph.D. Michael Janech, Ph.D. Edward Jauch, M.D. Diane Kamen, M.D., M.S.C.R. Michael J. Kilby, M.D. Louis Luttrell, M.D., Ph.D. Paul J. McDermott, Ph.D. Roberto Pisoni, M.D. Joseph Romagnuolo, M.D., M.Sc. Adam Smolka, Ph.D. Antine E. Stenbit, M.D., Ph.D. William Benjamin Wince, M.D. Xian (John) Zhang, Ph.D. Gerry Garza, M.B.A. Jill Griffith, M.B.A. Meghan Hatfield SPECIAL THANKS We would like to thank all the participants for sharing their innovative research, as well as those who coordinated and attended this event. Your support for our research mission is greatly appreciated. Sincerely, P. Darwin Bell, Ph.D. Vice Chairman for Research Professor, Nephrology Division Edward Jauch, M.D. Associate Vice Chairman for Research Professor, Emergency Med Division DEPARTMENT OF MEDICINE RESEARCH DAY AWARD RECIPIENTS 2006 Nathanael Pruett, Graduate Student, Rheumatology & Immunology Mi-Hye Lee, Ph.D., Postdoctoral Basic Science, Endocrinology Chamion Olivier, M.D., Clinical Fellow, Infectious Diseases Guangmao Cheng, M.D., M.S., Basic Junior Faculty, Cardiology JuanManuel Gomez, M.D., M.S.C.R., Clinical Junior Faculty, Infectious Diseases 2007 Arindam Saha, Graduate Student, Gastroenterology & Hepatology Santhosh Mani, Ph.D., Postdoctoral Basic Science, Cardiology Deepika Koya, M.D., Clinical Fellow, General Internal Medicine Hesham El-Shewy, Ph.D., Basic Junior Faculty, Endocrinology Joseph Romagnuolo, M.D., Clinical Junior Faculty, Gastroenterology & Hepatology 2008 Christopher Potter, Graduate Student, Rheumatology & Immunology Santhosh Mani, Ph.D., Postdoctoral Basic Science, Cardiology Eduardo Freitas, M.D., Clinical Fellow, Infectious Diseases Hesham El-Shewy, Ph.D., Basic Junior Faculty, Endocrinology Cassandra Salgado, M.D., Clinical Junior Faculty, Infectious Diseases Vidya Fleetwood, Medical Student, College of Medicine 2009 Jessica Trombetta, Graduate Student, Cardiology Santhosh K. Mani, Ph.D., Postdoctoral Basic Science, Cardiology Aisha Thomas, M.D., Clinical Fellow, Infectious Diseases Chris Parsons, M.D., Basic Junior Faculty, Infectious Diseases Cassandra Salgado, M.D., M.S.C.R., Clinical Junior Faculty, Division of Infectious Diseases John Lucas, Medical Student, College of Medicine MEET OUR 2010 AWARD WINNERS Denise Kimbrough Graduate Student Cardiology Takamitsu Saigusa, MD Clinical Fellow Nephrology (TIE) Courtney Haycraft PhD (Neph) & Patrick Nasarre PhD (Hem/Onc) Basic Science Junior Faculty Krupa Desai Medical Student Benjamin Neely, PhD Post-Doc, Basic Sci Nephrology Ashley Miller, NP Clinical Junior Faculty Hematology/Oncology (TIE) Infectious Disease & Rheumatology Division Participation Award Poster #1 В Urinary Angiotensinogen Predicts Acute Kidney Injury After Cardiac Surgery Alge, Joseph L.1, M.G. Janech1,2, A.D. Shaw3, L.S. Chawla4, J.A. Tumlin5 and J.M. Arthur1,2. 1 Department of Medicine, Division of Nephrology, Medical University of South Carolina; Ralph H. Johnson VA Medical Center, Charleston, SC; 3Department of Anesthesiology, Duke University Medical Center; 4Department of Anesthesiology and Critical Care Medicine and Division of Nephrology George Washington University; 5Department of Medicine, Division of Nephrology, University of Tennessee at Memphis 2 Acute kidney injury (AKI) is a common and serious post-operative complication of cardiac surgery that is associated with an increased risk of several adverse outcomes. The poor outcomes of these patients are partially attributable to the limitations of the current method of diagnosis, which is based upon an increase in serum creatinine (sCr). The discovery of novel biomarkers of AKI could improve patient outcomes by allowing for earlier and more accurate diagnosis and prognosis. Using a proteomic approach, we have identified novel candidate biomarkers of AKI. In this study, we validated one of these biomarkers, urinary angiotensinogen (uAng), in a set of samples that included pre-operative samples, post-operative samples from patients who did not develop AKI, and patients who developed AKI of increasing severity (stages I, II, and III). Ten patients developed severe AKI requiring renal replacement therapy (RRT). Patients with severe AKI had higher levels of uAng compared to the pre-operative group, and uAng was predictive of the progression of sCr elevation after urine collection (AUC= 0.66, Sensitivity= 74.4%, Specificity= 52.1%). However, it was not a good predictor of AKI, severe AKI, or the need for RRT. Importantly, however, we found that it was an excellent predictor of severe AKI (AUC= 0.86, Sensitivity=100%, Specificity= 70.1%), the need for RRT (AUC= 0.89, Sensitivity= 100%, Specificity= 81.8%), and the future increase of sCr (AUC= 0.74, Sensitivity=100%, Specificity= 64.3%) in the subset of patients who did not undergo intraoperative cardiopulmonary bypass (CPB). Analysis of paired pre-op and post-op samples suggested that CPB increased uAng. These results are the first to demonstrate the potential diagnostic and prognostic utility of uAng in patients at risk of renal injury. Graduate Student В Poster #2 Association of Willingness to Participate in Research Studies with Payment, Risk, and Time Among Individuals with Type 2 Diabetes Arnold Kimberly, Dismuke CE, Strom JL, Egede LE MUSC Department of Medicine, Division of General Internal Medicine and Geriatrics and the Ralph H. Johnson VAMC There are several factors that influence a patientвЂ™s willingness to participate in research studies including personal values, trust in the healthcare system, and an assessment of personal benefit (payment and risk). Bentley and Thacker (2004)9 found that monetary payment had positive effects on respondentsвЂ™ willingness to participate in research, regardless of risk, but it did not blind them to the risks involved in the studies. This study was conducted to discover the effects of payment, risk, and time on the willingness of patients with type 2 diabetes to participate in research studies. The hypothesis is patients will be more willing to participate in research studies with higher payment levels and lower levels of risk and time. A sample of 534 patients with type 2 diabetes was recruited from the MUSC University Internal Medicine Clinic, the Franklin C. Fetter Health System, and the Ralph H. Johnson VA Medical Center primary care clinic. To assess patient willingness to participate in research modules, subjects rated various research designs that involved different levels of risk, payment, and time. We used the Dickert and Grady model of payment for research from the study by Bentley and Thacker for this analysis. There was a negative correlation between risk and willingness with a Pearson correlation coefficient of -0.42862 and p value of 0.1262, but was not statistically significant at pв‰¤0.05. There was also a negative correlation between time and willingness with a Pearson correlation coefficient of -0.52286 and statistically significant p value of 0.0551. There was a positive correlation between payment and willingness with a Pearson correlation coefficient of 0.48885 and a p value of 0.0761, but was not statistically significant. The patients involved in this study were concerned with time more than payment or risk. Acknowledgements: NIH/NIDDK T35 DK007431-26 (09012151), Center for Health Disparities Research Classification: Student Type of Research Project: Clinical Science Email Address of Corresponding Author: stromjl@musc.edu Graduate Student Poster #3 В Effects of Fli-1 on T Cell Function in Lupus Basher, Fahmin (Dept. of Microbiology & Immunology, Dept. of Medicine/Div. of Rheumatology) Zainab Amani (Dept. of Medicine/Div. of Rheumatology) Marlene Bunni (Dept. of Medicine/Div. of Rheumatology) Tamara Nowling (Dept. of Medicine/Div. of Rheumatology, Ralph H. Johnson VA Medical Center) Lupus is an autoimmune disease characterized by abnormal activation of T and B cells and consequent production of autoantibodies, inflammation, and deposition of immune complexes in peripheral organs. Overexpression of the transcription factor Fli-1 in non-autoimmune mice leads to a lupus-like disease state, while reduction of Fli-1 expression results in decreased T cell infiltration in the kidney as well as decreased inflammation and increased survival. In this study we investigated effects of Fli-1 on T cell function in both non-autoimmune (C57BL/6) and autoimmune (MRL/lpr) mouse models with respect to proliferation and apoptosis after stimulation with PMA/ionomycin. While a decrease in proliferation was seen in wildtype B6 mice compared to Fli-1+/-, no differences were observed in pre-disease MRL mice, and proliferation seemed to be driven primarily by CD8+ cytotoxic cells. Fli-1вЂ™s known antiapoptotic effects were observed in the B6 mice, with a decrease in early apoptosis in wildtype mice compared to Fli-1+/-, and a similar trend was seen in the MRL model, with CD4+ cells exhibiting increased and CD8+ cells decreased early apoptosis. We adoptively transferred T cells isolated from young wildtype MRL/lpr mice into Fli-1+/- mice, and vice versa and monitored serum antibodies and proteinuria over 12 weeks. IgG levels in Fli-1+/- mice receiving wildtype cells, and wildtype mice receiving Fli-1+/- cells exhibited a modest increase but still significantly lower than wildtype controls, and this trend was also seen in the anti-dsDNA, antiGBM, and proteinuria studies. Conversely, IgM levels did not differ significantly between wildtype and Fli-1+/- recipients, and transfer of Fli-1 +/- cells to either Fli-1+/- or wildtype recipients resulted in increased IgA levels. These results indicate that presence of lower levels of Fli-1 in endogenous or transferred T cells can protect from disease with respect to circulating antibodies such as IgG but that reduced expression of Fli-1 may limit class switching to IgG from other subclasses. Category: graduate student (basic science) Graduate Student В Poster #4 В Lupus Sera from Patients with Interferon Signature Impairs Endothelial Nitric Oxide Synthase Expression in Human Endothelial Cells Buie, Joy (Presenting Author/Student)1,2, Jim Oates1,2,3 Department of Microbiology and Immunology, College of Graduate Studies, MUSC Charleston, SC1 Division of Rheumatology and Immunology2, Ralph H. Johnson VA Medical Center, Charleston, SC3 Background and Significance: Late stage clinical mortalities in systemic lupus erythematosus (SLE) are attributed to myocardial infarction and heart disease. Preclinical disease presentation includes decreased flow mediated dilation (FMD), a surrogate marker of endothelial dysfunction (ED). Pathways leading to ED converge on the diminished activity of endothelial nitric oxide synthase (eNOS) and loss of endothelial derived nitric oxide (eNO). Interferon alpha gene expression is increased in circulating immune cells in lupus patients, and recent studies suggest that decreased FMD correlates with increased interferon alpha signature gene expression in circulating endothelial progenitor cells (EPCs), increased EPC apoptosis, and an overall decline in circulating EPCs, resulting in impaired blood vessel repair. However, interferon alphaвЂ™s effect on endothelial cell (EC) eNOS remains to be unveiled. Hypothesis: We hypothesized that interferon alpha, present in SLE sera from patients with interferon signature genes, would cause a reduction in eNOS expression and activation in human endothelial cells. Methods: Cultured human ECs and WISH cells (IFNО± reporter cells) were preconditioned in SLE (n=4) and control (n=1) serum. Cells were also treated with IFN alpha at 100 and 1000 international units (IU). Transcript levels of eNOS and IFNО± response genes were measured at 6,12, and 24 hrs while protein expression levels were measured at 24 hours by Western blot. Results: Reverse transcriptase-real time polymerase chain reaction (RT2-PCR) studies showed a 76% reduction in eNOS expression compared to buffer controls and a 20% reduction compared to cells preconditioned in normal sera. While eNOS protein levels were similar in all sera treated cells, lupus sera treatment decreased Ser 1177 phospho-eNOS (activated eNOS) protein by 31% when compared to protein levels in normal control conditioned cells. Lupus sera samples induced an interferon response gene signature in both the endothelial cells and WISH cells, a cell line designed to detect the presence of IFNО± in serum samples. Thus, we examined the effects of pure interferon on eNOS gene expression at 12 and 24 hours. For the first time, we showed that after 24 hours, eNOS is reduced more than 50 fold in cells treated with 100 IU and 1000 IU of IFN-alpha. Conclusion: Collectively, these studies indicate that SLE serum causes a reduction in peNOS protein expression, and eNOS mRNA expression at 24 hrs. These data suggest that interferon alpha overexpression may be responsible for decreases in eNOS expression and ultimately endothelial dysfunction in lupus patients. Type of Research: Basic Science Email Address of Corresponding Author: jonejn@musc.edu Graduate Student В Poster #5 В The Role of Estrogen-Related Receptors in Cardiomyocyte Metabolic Adaptation to Oxidative Stress Cribben, Kathryn ( cribben@musc.edu, College of Grad Studies), P.McDermott (Department of Medicine, VA Medical Center Investigator) Keywords: cardiomyocyte, metabolism, hypoxia, estrogen-related receptor Introduction: In the ischemic heart, metabolic adaptation of the cardiomyocyte to hypoxia is critical to sustain myocardial structure and function. These metabolic adaptations are dependent on Estrogen-Related Receptors (ERRs), which are members of the nuclear hormone receptor superfamily of transcription factors. ERRs regulate expression of genes involved in fatty acid metabolism, oxidative phosphorylation, and mitochondrial biogenesis. The purpose of these studies is to determine the regulatory mechanisms governing expression of the alpha, beta and gamma isoforms of ERR in cardiomyocytes undergoing oxidative stress. Methods: Adult feline cardiomyocytes in primary culture were electrically stimulated to contract at 1 Hz under normoxia (21% oxygen), hypoxia (0.5% oxygen), or hypoxia followed by reoxygenation. Expression of ERR isoforms and target genes was measured by QRT-PCR. Distribution of mRNA-ribosomal complexes was measured by fractionation of polysomes on a linear sucrose gradient. SABiosciences QRT-PCR arrays provided a high throughput tool for prospective target gene identification. Results: Expression of ERR-alpha mRNA was significantly increased by 3.5-fold over 24 hours of hypoxia compared to normoxic controls. In contrast, ERR-beta mRNA expression increased 11-fold after 12 hours of hypoxia, and this increase was maintained over 24 hours. Subsequent reoxygenation for 24 hours caused a partial (25%) reduction in ERR-alpha expression, but ERR-beta expression returned to baseline levels. Hypoxia also increased mRNA expression of PGC-1alpha, an ERR co-activator, by16-fold over 24 hours, while reoxygenation reduced expression back to baseline levels by 24 hours. Conclusions: 1) Hypoxia in cardiomyocytes induced rapid and substantial increases in ERR-beta and PGC-1alpha expression compared to ERR-alpha expression; 2) reoxygenation returned expression of ERR-beta and PGC-1alpha to baseline levels; 3) hypoxia caused a smaller, yet sustained increase in ERR-alpha expression. Acknowledgements: This research was funded by the NIH Predocotoral Fellowship Training Grant to Improve Cardiovascular Therapies, and the Merit Review Award of the Department of Veterans Affairs. Graduate Student В Poster #6 Seamless Phase II/III Adaptive Dose Finding Design for Longitudinal Data in Safety/Efficacy Clinical Trials Ellerbe, Caitlyn N, Biostatistics and Epidemiology, MUSC Authors: Ellerbe, Caitlyn N, Elm, J., Ramakrishnan, V., Durkalski, V., Biostatistics and Epidemiology, MUSC Abstract: Randomized controlled trials (RCT) remain the gold standard for FDA investigational new drug or new device certification. Computational advances, have allowed for adaptive trial designs which modify trial parameters in an effort to increase safety and trial efficiency. Adaptive trials differ from traditional fixed design trials in that they can pre-specify design features such as sample size, study population and randomization ratios, which may be modified in response to the observed data or outside information while the trial is in progress. Although compelling, clinicians, regulatory bodies and biostatisticians are reticent to implement these designs due to uncertainties with respect to the validity, implementation, and interpretation of adaptive trials. Our goal is to propose an adaptive design that takes into account the accruing data and examine its operating characteristics in terms of type I error and power. In many disease settings clinicians have lingering questions as to the relationship between efficacy and safety that cannot be evaluated in a small phase I patient population. Consider a trial in which there are three doses of interest and a placebo control, as the dose increases efficacy may increase but more adverse events may also be observed. A seamless phase II/III placebo controlled trial to evaluate the safety and efficacy of these doses and confirm the benefit of the optimal dose has been proposed. This design addresses key clinical issues such as: a) most efficacious treatment arm for a confirmatory phase; b) inclusion of covariates; c) incorporation of earlier surrogate endpoint information; d) response adaptive randomization; e) early stopping for futility and f) clinical advice. Funding: Net-PD: NINDS U01NS043127, NETT: NINDS U01 NS059041 Email: ellerbcn@musc.edu Scientific Topic: Biostatistics Graduate Student Poster #7 Patient acceptance as a barrier to HIV screening in a tertiary care emergency department. Green, Michael, Shapshak D, Glover N, Navarro B, Houck R, Fesperman C. Division of Emergency Medicine, Department of Medicine. Objective: Assess patient acceptance of routine no-cost HIV-screening in an ED setting Methods: The MUSC Emergency Department is an academic, tertiary care facility with a 40 bed capacity. From May 2008 to November 2011, MUSC offered routine, non-targeted testing at no cost for emergency department patients aged 18 to 64. Trained research assistants offered UniGoldв„ў RecombigenВ® HIV rapid immunoassays to patients during their ED treatment course. Reasons patients declined testing were documented and categorized. These categories include: previously tested positive, tested negative within 6 months, not at risk, monogamous, afraid or no reason. Results: Of 10985 patients approached, 7543 accepted testing. There were 3442 patients who declined testing for the following reasons: 175 patients cited вЂњpreviously positiveвЂќ; 1618 cited вЂњrecent testвЂќ; 336 cited вЂњno risk,вЂќ333 cited вЂњmarried/monogamousвЂќ; 60 cited вЂњafraid.вЂќ Three hundred and forty patients provided reasons categorized under вЂњother,вЂќ and 589 declined to provide a reason. The acceptance rate among allвЂ“comers was 69%. Among patients without a prior positive test, the acceptance rate was 85%. Conclusions: Patient participation is essential for the sustainability of any testing program. An acceptance rate of 85% suggests ED patients are willing to participate in bedside, rapid HIVscreening offered at no cost. The 31% refusal rate appears inflated because the inclusion of the 16% of patients who previously accepted testing. Only 6% of patients refused testing due to the perception they were not at risk with less than 1% admitting they were вЂњafraidвЂќ of the test result. Focusing on education regarding HIV risk factors may enhance participation. Lack of patient acceptance is not a relevant barrier to the success of our ED testing model. The corresponding author: Dag Shapshak MD (shapshak@musc.edu) Type of Research: Clinical Graduate Student Poster #8 В Fli-1 transcription Factor Affects Glomerulonephritis Development by Regulating Expression of Inflammatory Chemokine in Endothelial Cells in Kidney Karam, Eva1, Eiji Suzuki1, Sarah Williams2, Xian Zhang1, 2 1 Division of Rheumatology & immunology, Department of Medicine. Med. Univ. of South Carolina, Charleston, SC, 2Ralph H. Johnson VA Medical Center, Charleston, SC Expression of Fli-1, a member of the Ets family of transcription factors, is implicated in the development of glomerulonephritis in murine models of systemic lupus erythematosus (SLE). Lupus nephritis is a major cause of death in both animal models and human patients, and is characterized by immune complex formation and inflammatory cell infiltration. Expressions of monocyte chemotactic protein-1 (MCP-1) and Chemokine (C-C motif) ligand 5 (CCL5) has been demonstrated to initiate inflammatory cell infiltration in the kidneys of lupus mice. In this study, we examined the role of Fli-1 on chemokine production and inflammatory cell infiltration in conjunction with nephritis development in NZM2410 mice, an animal model of SLE. We generated Fli-1 heterozygous knockout NZM2410 mice (Fli1+/-) and wild-type (WT) littermate (Fli1+/+) mice. The expression levels of MCP-1 and CCL5 in the kidneys from 18-week-old mice were analyzed by real-time PCR and it was found that there was a significant reduction in MCP-1 and CCL5 expression in Fli-1 heterozygous knockout NZM2410 mice (Fli1+/-) when compared to WT littermate (Fli1+/+). We then examined the expression of MCP-1 in endothelial cells isolated from the kidneys of both Fli-1+/- and WT controls. We found that there was a significant reduction in MCP-1 production from endothelial cells isolated from the kidneys of Fli-1+/- NZM2410 mice compared to those isolated from WT NZM2410 mice kidney. Next, we studied the production of MCP-1 and CCL5 from endothelial cells transfected with specific Fli-1 siRNA. There was a significant reduction in MCP-1 and CCL5 production from cells transfected with the specific Fli-1 siRNA when compared to cells transfected with negative control siRNA. Our data indicates that Fli-1 affects glomerulonephritis development by regulating expression of inflammatory chemokine MCP-1 and inflammatory cell infiltration in the kidneys. The lower expression of Fli-1 resulted in decreased expression of MCP-1 in kidney endothelial cells which significantly reduced infiltration of inflammatory cells, which led to reduced glomerulonephritis in NZM2410 mice. This study was supported by National Institutes of Health grants (AR056670 to X.Z.) and the Medical Research Service, Department of Veterans Affairs (to X. Z.). Graduate Student В Poster #9 Inhibition Of Histone Deacetylase Activity Represses Matrix Metalloproteinase-9 Induction by Regulating of Macrophage Secretion of MMPs to Preserving Extracellular Matrix Post Myocardial Infarction Kimbrough, Denise, Santhosh K. Mani*, Christine B. Kern*, Benjamin Addy, William T. Rivers#, Francis G. Spinale#, Rupak Mukherjee# and Donald R. Menick*. Departments: *Gazes Cardiac Research Institute, Department of Medicine, Division of Cardiology, #Department of Surgery, Medical University of South Carolina, Charleston, SC The cardiac extracellular matrix (ECM) consists of a dense network of collagens to which matrix components such as fibroblast and myocytes attach to maintain cardiac function. Postmyocardial infarction (MI) the ECM undergoes massive remodeling in order to prevent dilation of the infarct area and maintain cardiac output. This remodeling includes three phases: inflammation, proliferation/granulation, and mature scar formation. Integral players in this remodeling are matrix metalloproteinases (MMPs). Post-MI macrophages are a significant source of MMP production and have been shown to have temporal expression of the two subtypes (M1 and M2). Differential expressions of macrophage subtypes correlate with the different phases of ECM remodeling, ECM composition and MMP expression. Increased expression of MMP-9 and MMP-2 is associated with deleterious effects to the ECM and left ventricular (LV) dilation following MI. Histone deacetylases (HDACs) are a class of enzymes that can greatly affect transcriptional regulation of genes during pathological conditions. We hypothesize that HDACs regulate MMP-2 and -9 in the post-MI heart through mediating cytokine expression and the M1 and M2 polarization. MI was induced in transgenic mice with the MMP-9 promoter sequence fused to the Beta-galactosidase (Beta-gal) gene. Twelve hours prior to MI, mice were administered the HDAC inhibitor trichostatin A (TSA, 2 mg/kg/day) or vehicle. TSA (n=28) or vehicle treatment (n=23) continued until hearts were harvested 7 days post-MI. The post-MI change in LV end-diastolic volume was significantly lower in the TSA treated mice (49В±9%) than in mice administered vehicle (69В±12%). Similarly, ejection fraction was also improved in the TSA treated mice (-44В±8%) when compared to vehicle (-59В±6%). Beta-gal staining of the post-MI LV was lower in the TSA mice compared to vehicle. Zymographic levels of MMP-9 were lower with TSA than in vehicle. There is increased periostin accumulation in the infarct zone compared to remote zone post-MI at day 1 and day 4. The majority of MMP-9 expression at 7 days post MI is from infiltrating macrophages with some contribution from resident fibroblasts. TSA treatment of cultured macrophages and isolated human cardiac fibroblasts repressed MMP-9 induced expression. From these data we conclude that macrophage secretion of MMPs is an essential component in the promotion of adverse ECM remodeling post-MI and that HDAC inhibition can attenuate this remodeling and that macrophage polarization plays an essential role in this attenuation. Student, Basic science, Email: kimbroug@musc.edu Graduate Student В Poster #10 В Glucosylceramide and lactosylceramide accumulation in lupus nephritis: biomarker or mediator of disease? Mather, Andrew R.1, Jennifer Schepp-Berglind2, MarГa JosГ© Hernandez-Corbacho2, Jon M. Donahue2, Ashley J. Snider2,3, Jim C. Oates2,3, and Leah J. Siskind1,2,3 Departments of 1Biochemistry and Molecular Biology and 2Medicine Medical University of South Carolina, Charleston, SC 3 Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC Systemic lupus erythematosus (SLE) is a chronic autoimmune disease in which the immune system attacks otherwise healthy tissue causing inflammation and damage in various parts of the body including the kidney. SLE manifests in a variety of ways including the development of lupus nephritis in roughly 50% of patients. Current therapies have a low success rate along with infectious and reproductive side effects. Thus, more effective and less toxic therapies for lupus nephritis are in high demand. Glycosphingolipids are highly abundant in the kidney and play an important role in a variety autoimmune as well as kidney diseases. However, the role of glycosphingolipids in lupus nephritis is unknown. We utilized the MRL/lpr lupus nephritis mouse model to test the hypothesis that the glycosphingolipids glucosylceramide (Glucer) and lactosylceramide (LacCer) play a role in lupus nephritis. Our data demonstrate accumulation of both GluCer and LacCer within the kidney cortices of lupus mice via multiple approaches, including mass spectrometry, immunohistochemistry, and flow cytometry. In addition, these glycosphingolipids are excreted into the urine prior to the onset of proteinuria. Interestingly, the expression and activity of neuraminidases are significantly elevated in lupus nephritis mice, suggesting that ganglioside breakdown is the mechanism by which GluCer/LacCer accumulate. In addition, humans with lupus nephritis have significantly higher levels of glycosphingolipids in their urine as compared to those found in normal patients and non-nephritis lupus patients. Thus, the data suggest that glycosphingolipids may be an important biomarker or even mediator of lupus nephritis. Specifically, two FDA approved drugs used for the treatment of GaucherвЂ™s disease and influenza are available that inhibit neuraminidases involved in the metabolism of these glycosphingolipids showing that results from the above studies could be rapidly translated to humans for the treatment of lupus nephritis. This work is supported by the following grants: VA CDA-2 (to LJS, AJS), VA REAP (to LJS, AJS, JO), COBRE (to LJS, AJS), Alliance for Lupus Research (to JO) Graduate Student В Poster #11 В Effects of Perfluorooctane Sulfonate (PFOS) and Perfluorooctanoic Acid (PFOA) on IL-2 Production in the Human Jurkat T-cell Line Midgett, Kristin Smith1, Margie Peden-Adams2, Gary S. Gilkeson3,4, Diane L. Kamen3 1 Department of Immunology and Microbiology, Medical University of South Carolina; 2Harry Reid Center for Environmental Studies, University of Nevada-Las Vegas; 3Division of Rheumatology and Immunology, MUSC; 4Ralph H. Johnson VAMC, Charleston, SC The potential human health effects of perfluorinated compounds such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are becoming an increasing concern in the United States and worldwide. Both PFOS and PFOA have been shown to alter various immune functions suggesting that they are immunotoxic. PFOS specifically has been shown in rodent studies to decrease T-cell IL-2 production, which is characteristic of autoimmune diseases such as systemic lupus erythematosus (SLE). Along with PFOS, PFOA has been detected in human blood, but had not previously been investigated for modulation of IL-2 production. The current study assessed the effects of PFOS and PFOA on IL-2 production in the human Jurkat T-cell line. Cells, stimulated with PHA/PMA or anti CD-3/anti CD-28, were dosed with 0, 0.05, 0.1, 0.5, 1, 5, 10, 50, 75, or 100 ug/ml of PFOS or 0, 0.005, 0.01, 0.05, 0.1, 0.5, 1, 5, or 10 ug/ml of PFOA. Jurkat cells stimulated with PHA/PMA exhibited decreased IL-2 production beginning at 50 ug PFOS/ml. However, cells stimulated with anti-CD3/anti-CD28 exhibited no alteration in IL-2 production. PFOA exposure in cells stimulated with PHA/PMA resulted in significant decreases in IL-2 production at 10 ug PFOA/ml, but cells stimulated with anti-CD3/anti-CD28 exhibited no alteration in IL-2 production. Addition of the PPAR-alpha antagonist GW6471 to PFOS dosed cells stimulated with PHA/PMA resulted in decreases in IL-2 production starting at 50 ug PFOS/ml. However, the addition of GW6471 to PFOA exposed cells stimulated with PHA/PMA ameliorated the PFOA-induced decrease in IL-2 production. These data suggest that PFOS affects T-cell IL-2 production via PPAR-alpha-independent mechanisms and that PFOAinduced suppression of IL-2 production may be PPAR-alpha-dependent. Further studies utilizing cells from SLE patients who have varying blood levels of PFOS and PFOA are underway to further investigate the role of PFOS and PFOA as environmental triggers of SLE. This project was supported by the South Carolina Clinical & Translational Research (SCTR) Institute at the Medical University of South Carolina, NIH/NCRR Grant number UL1 RR029881 and Diane KamenвЂ™s NIH/NIHES 1 R21 ES017934-01 Grant. Graduate Student В Poster #12 В mTORC2-mediated Prosurvival Signaling Requires PKCОµ in Adult Feline Cardiomyocytes Pleasant, Dorea L., Phillip Moschella, John McKillop, Sundaravadival Balasubramanian and Dhandapani Kuppuswamy. Department of Medicine, Division of Cardiology, Medical University of South Carolina, Charleston SC. Cardiac hypertrophy occurs in response to stress, such as an increase in hemodynamic overload. Our laboratory has shown that mammalian target of rapamycin (mTOR) is essential to the development of various hypertrophic responses, including cardiomyocyte survival. mTOR forms two independent complexes, mTORC1 and mTORC2, by associating with common and distinct cellular proteins. Both complexes are sensitive to a pharmacological inhibitor, torin, although only mTORC1 but not mTORC2 was sensitive to rapamycin inhibition. Since our earlier work shows that mTORC2 regulates the activation of a prosurvival kinase Akt, we initiated a study to characterize whether mTORC2 directly mediates Akt activation or whether it requires the participation of another prosurvival kinase PKCОµ (epsilon isoform of protein kinase-C). Our present work reveals that treatment of adult feline cardiomyocytes with insulin results in the phosphorylation of Akt at S308 and S473 sites for its activation which could be blocked by pretreatment with torin but not with rapamycin. Furthermore, silencing the expression of a mTORC2 component, Rictor (rapamycin-insensitive companion of mTOR), with sh-Rictor also lowers insulin-stimulated Akt activation. These studies demonstrate that insulin-stimulated Akt phosphorylation in cardiomyocytes is mediated primarily via mTORC2. Next, we explored if PKCОµ plays a role in the mTORC2-mediated Akt activation by expressing a dominant negative isoform of PKCОµ (DN-PKCОµ) in cardiomyocytes. DN-PKCОµ expression was found to significantly lower insulin-stimulated Akt activation. Furthermore, immunoprecipitation combined with Western blot analyses revealed that PKCОµ was part of rictor but not raptor (a binding partner and component of mTORC1), and phosphorylation of PKCОµ at the critical S729 site for its activation was found to be blocked by torin. Together, these studies clearly demonstrate that mTORC2 mediates prosurvival signaling during insulin stimulation in adult cardiomyocytes where PKCОµ activation downstream of mTORC2 is critical for the activation of Akt. Type of Research: Basic Science Corresponding Author: kuppusd@musc.edu Graduate Student В Poster #13 Does Acetylation Regulate miRNA Expression in Myocardial Infarction? Renaud, Ludivine (PhD student, basic science), Harinath Kasiganesan, Erhe Gao#, Santhosh K. Mani, Jeffrey A. Jones*, Robert E. Stroud*, Donald R. Menick Department of Medicine * Department of Surgery, MUSC, Charleston, SC # Thomas Jefferson University, PA Cardiovascular diseases are one of the leading causes of morbidity and mortality in the world, underlining the need for innovative therapies and diagnosis for heart disease. MicroRNAs (miRNAs) have been identified as central players in regulating gene expression. miRNAs are noncoding RNAs that bind to target mRNAs and reduce their expression. Several recent reports have demonstrated that some miRNAs are aberrantly expressed in cardiac arrhythmia, hypertrophy, fibrosis, ischemia, vascular atherosclerosis and heart failure. Histone deacetylase (HDACs) are a class of enzymes that affect the transcriptional regulation of genes during pathological conditions. Previous studies in our laboratory demonstrated that 1) class I and class II HDACs play an important role in the basal expression and upregulation of the sodium calcium exchanger (Ncx1) gene in adult cardiomyocytes and 2) treatment with HDAC inhibitors trichostatin (TSA) or SAHA improved ventricular function by suppressing MMP9 gene expression in MI. Both TSA and SAHA inhibit class I and class IIb HDACs specifically and SAHA is currently FDA approved for T-cell lymphoma treatment. We hypothesize that SAHA treatment will ameliorate the shift in expression of some of the miRNA which are misregulated in MI. Ligation of the left anterior descending (LAD) coronary artery was performed to induce MI using a novel surgical procedure (Gao et al. 2010) which is less invasive than the conventional protocol: in less than 2.5min/mouse, the heart is popped out of the chest through a very small incision between 2 ribs and ligation of the LAD artery is done before pushing the heart back inside the chest. Mice were divided into 4 treatment groups: SHAM control, MI-7days, MI-7days+SAHA-day0, MI-7days+SAHA-day1. We examined the expression level of miRNAs that have been shown previously to be aberrantly expressed in MI. RT-PCR demonstrated that miR-1, miR-29a, miR-133a, miR208a and miR-486 are decreased and miR-21 is increased by 10 fold 7 days post-MI. Interestingly, SAHA treatment significantly attenuated the abnormal expression of miR21. miR-21 has been shown to regulate PTEN and indirectly MMP2 expression, and to contribute to post-MI deleterious pathological remodeling. Our preliminary data confirm this finding and demonstrate that inhibition of HDACs may provide a novel therapeutic strategy to attenuate adverse post-MI remodeling. NIH RO1 HL066223, AHA Grand in Aid 09GRNT2020202 Gao, E., Y. H. Lei, X. Shang, Z. M. Huang, L. Zuo, M. Boucher, Q. Fan, J. K. Chuprun, X. L. Ma and W. J. Koch (2010). "A Novel and Efficient Model of Coronary Artery Ligation and Myocardial Infarction in the Mouse / Novelty and Significance." Circulation Research 107(12): 1445-1453. Corresponding author: Ludivine Renaud renaudl@musc.edu Graduate Student Poster #14 The Analysis of Acute Stroke Clinical Trials with Responder Analysis Outcomes Robinson, Kyra M -Division of Biostatistics and Epidemiology, MUSC Sharon D Yeatts-Division of Biostatistics and Epidemiology, MUSC Viswanathan Ramakrishnan-Division of Biostatistics and Epidemiology, MUSC Valerie L Durkalski-Division of Biostatistics and Epidemiology, MUSC Traditionally in acute stroke clinical trials, the primary outcome has been a dichotomized modified Rankin scale (mRS). The mRS is a 7-point categorical scale indicating a patientвЂ™s level of disability following a stroke. Standard practice uses a fixed dichotomization scheme, which dichotomizes вЂ�successвЂ™ as an mRS of 0-1 (or 0-2). This method fails to address the concern that stroke severity may impact the likelihood of a successful outcome; subjects with mild baseline stroke severity may achieve the defined threshold for success more easily than subjects with severe baseline stroke severity 1 . As a consequence, subjects are not able to contribute equally to the estimation of treatment effect. Stroke studies are increasingly turning to new methods that make more efficient use of the available data. These new methods include responder analysis, the global statistic, and shift analysis 2 . The focus of this study is responder analysis, in which the definition of success varies according to baseline severity. Through the use of this sliding dichotomization scheme, responder analysis puts stroke patients on a more level playing field, producing a more precise insight into the actual effect of investigational stroke treatments 2 . It is unclear whether or not statistical analyses should adjust for baseline severity when responder analysis is used, as the outcome already takes into account baseline severity. In this simulation study, we compare the power and type-I error rates of adjusted and unadjusted analyses of both a fixed dichotomization scheme and a sliding dichotomization scheme like that seen in responder analysis. The results of this study will help delineate the best way to handle such analyses in stroke studies and will be used to guide analyses for future stroke trials. This work is funded by the National Institute of Neurological Diseases and Stroke through grant U01 NS069498-01. Graduate student poster presentation Type of research project: Biostatistics Corresponding author: Kyra M Robinson, robinskm@musc.edu 1 Murray GD, Barer D, Choi S, Fernandes H, Gregson B, Lees KR, Maas AI, Marmarou A, Mendelow AD, Steyerberg EW, Taylor GS, Teasdale GM, Weir CJ. Design and analysis of phase III trials with ordered outcome scales: the concept of the sliding dichotomy. J Neurotrauma. 2005; 22: 511-517. 2 Saver, JL. Novel end point analytic techniques and interpreting shifts across the entire range of outcome scales in acute stroke trials. Stroke. 2007; 38: 3055-3062. Graduate Student Poster #15 Associations between Coping Styles, Diabetes Knowledge, Medication Adherence, and Self-Care Behaviors in Adults with Type 2 Diabetes Smalls, Brittany, Walker RJ, Hernandez-Tejada MA, Campbell JA, Davis KS, Egede LE MUSC Department of Medicine, Division of General Internal Medicine and Geriatrics Literature on diabetes and psychological factors show that some actions and thoughts that compose coping styles relate to compliance with treatment and self-care prescriptions. The goal of this study is to examine different coping styles and how these are related to diabetes management in adults with type-2 diabetes. The study had 378 subjects, recruited from the MUSC Internal Medicine Clinic and Franklin C. Fetter Health Center, who completed the following measures: 24-item diabetes knowledge questionnaire, Summary of Diabetes SelfCare Scale, COPE-S, and the 8-item emotional-approach coping questionnaire. Our study population was comprised of 83% Non-Hispanic Blacks, 69% women, 22% 65 years or older, 68% were not married, 26% had <high school education, 60% unemployed, 39% uninsured, 47% had a yearly income of <$10,000, and 24% had worsening health status. Significant correlations were observed between both types of coping: emotional expression (EE) and emotional processing (EP) (r=0.070, p<0.0001). EE was related to diabetes knowledge (r=0.18, p<0.001) and EP to foot care (r=0.14, p<0.015). However, both were related to diet (EE r=0.18, p<0.001; r=0.16, p<0.005); exercise (EE r=0.20, p<0.004; EP r=0.23, p<0.001); and blood sugar testing (EE r=0.13, p<0.023; EP r=0.15, p<0.008). In the linear regression model, EP was significantly associated with medication adherence (ОІ 0.17, 95% -0.32, -0.015), diabetes knowledge (ОІ 0.76, 95% 0.29, 1.24), diet (ОІ 0.52, 95% 0.24, 0.81), exercise (ОІ 0.51, 95% 0.19, 0.82), blood sugar testing (ОІ 0.54, 95% 0.16, 0.91), and foot care (ОІ 0.32, 95% -0.23, 0.67). Contrarily, EE was associated with diet (ОІ 0.38, 95% 0.13, 0.64), exercise (ОІ 0.54, 95% 0.27, 0.82), blood sugar testing (ОІ 0.42, 95% 0.00, 0.76) and foot care (ОІ 0.36, 95% 0.60, 0.66), but was not associated with diabetes knowledge. In conclusion, coping styles related to emotional processing and emotional expression was significantly associated with improved diabetes management. Acknowledgements: NIH T35DK007431, Center for Health Disparities Research Classification: Graduate Student Type of Research Project: Clinical Science Email Address of Corresponding Author: smallsbr@musc.edu Graduate Student Poster #16 В SPARC has a Two-Fold Mechanism to Maintain Periodontal Ligament Integrity Trombetta-eSilva, Jessica 1,2 and Amy D. Bradshaw1,2,3 1 3 Department of Craniofacial Biology, 2Department of Medicine: Division of Cardiology, Ralph H. Johnson VA The periodontal ligament (PDL) is a unique tissue that maintains the tooth within the alveolar bone. PDL is primarily composed of collagen type I, produced by resident fibroblasts. PDL extracellular matrix (ECM) has a high turnover rate, thus PDL is a prime tissue to study collagen deposition and remodeling. Collagen binding proteins, such as SPARC, are critical in collagen secretion and incorporation into the ECM. SPARC is a matricellular protein with anti-proliferative and counter-adhesive properties. SPARC-null PDL has significant deficiencies in collagen volume fraction, thickness, and overall morphology as compared to WT PDL. In a periodontal disease model, lipopolysaccharide was injected between the first and second molars of WT and SPARC-null mice to induce local inflammation. In this model, as compared to WT, SPARC-null mice lost a significant amount of alveolar bone and PDL collagen, despite decreased inflammation. To address cellular mechanisms of decreased homeostatic collagen content and response to disease in the absence of SPARC, we cultured PDL fibroblasts and used a novel organ culture model. Our preliminary results demonstrated, both in vitro and ex vivo, that SPARC-null PDL fibroblasts had a deficiency in procollagen processing, as indicated by an accumulation of procollagen in SPARC-null cells and tissue that was not evident in WT conditions. Furthermore, increases in procollagen were found associated with cell surfaces in the absence of SPARC. In addition, using similar models we examined the enzyme transglutaminase, known to catalyze covalent cross-links in the ECM. Utilizing the organ culture model we established SPARC as a potential transglutaminase inhibitor. Taken together, these data suggest SPARC is involved in both procollagen processing and in collagen stabilization via cross-link formation in the PDL. Presenting Author: Graduate Student Basic Science Research Project Corresponding Author: trombet@musc.edu Graduate Student В Poster #17 Association between Fatalism, Medication Adherence and Self-care behaviors in Adults with Type 2 Diabetes Walker, Rebekah, Smalls BL, Hernandez-Tejada MA, Campbell JA, Davis KS, Egede LE MUSC Department of Medicine, Division of General Internal Medicine and Geriatrics Fatalism refers to a complex psychological cycle characterized by perceptions of hopelessness, meaninglessness, powerlessness, and despair (Powe and Weinrich, 1999; Egede and Ellis 2009). Few studies have examined the effect of fatalism on health outcomes. The objective of this study was to examine the association between fatalism and medication adherence and self-care behaviors in adults with diabetes. Data on 378 subjects with Type 2 diabetes were examined. Fatalism was measured with a 12-item scale; medication adherence was assessed with the 4-item Morisky scale; diabetes knowledge was measured with a 24-item diabetes knowledge questionnaire; and self-care behaviors were assessed with the Summary of Diabetes Self-care Scale. Multiple linear regression was used to assess the independent effect of fatalism on medication adherence and self care controlling for covariates. Subject description is as follows: 83% were NonHispanic Blacks, 69% were women, 22% were 65 years or older, 26% had less than high school education, 60% were unemployed, 61% were insured, 47% had a yearly income <$10,000, and 24% had worsening health status. Fatalism correlated significantly with medication adherence (r = 0.24, p<0.001), diet (r=-0.26, p<0.001), exercise (r=-0.20, p<0.001), blood sugar test (r=-0.19, p<0.001); however there was not significant association with diabetes knowledge or foot care. In the linear regression model, fatalism was significantly associated with mediation adherence (ОІ 0.24, 95% CI 0.010, 0.038); diet (ОІ -0.05, 95% CI -0.077, -0.027), exercise (ОІ -0.04, 95% CI -0.067, -0.011), and blood sugar test (ОІ -0.05, 95% CI -0.08, -0.013); however, there was not significant association with knowledge or foot care. In this group, fatalism largely predicted poorer health behaviors. Thus, fatalism may be an important aspect of patient psychology to consider when designing interventions, and patients with this personality characteristic or life outlook may benefit from specific intervention. Acknowledgements: NIH/NIDDK T35DK007431, Center for Health Disparities Research Classification: Graduate Student Type of Research Project: Clinical Science Email Address of Corresponding Author: walkerrj@musc.edu Graduate Student Poster #18 Effect of Locus of Control on Clinical Outcomes for Diabetes Ashley Bryan, Hernandez-Tejada MA, Strom JL, Egede LE MUSC Department of Medicine, Division of General Internal Medicine and Geriatrics and the Ralph H. Johnson VAMC Diabetes, like many chronic diseases, requires important behavioral changes to be successfully treated. Thus, the impact of cognitive and behavioral traits on glycemic control is large. Locus of control (LOC), referring generally to how much control one perceives over oneвЂ™s health, appears related to positive health outcomes. Specifically, the internal dimension of LOC (i.e., believing one can actually exert influence on oneвЂ™s health outcomes) is most related to outcomes in prior research. The goal of this study was to establish the association between an individualвЂ™s locus of control and glycemic management. Surveys were collected in three different clinics in the Charleston, SC and included an 18 question Multi-dimensional Health Locus of Control questionnaire. LOC scores were categorized as internal, other people, chance, and doctors. 45% of patients were 50-64 years old, 66% were black, 56% male, 60% were married, 35% completed High School and 34% had some college, 76% were unemployed, 35% earned less than $10,000 annually. Analyses were conducted with participant responses for which data was available for a particular variable (N range: 605 вЂ“ 683 across variables). Multiple linear regression indicated that the internal LOC accounted for about 11% of the change in LDL (beta 0.71, 95% 0.15, 1.26), however no association was noted between LOC and HbA1c. This lack of association may be due to the length of survey, comprehension of the instructions, and HbA1c taken from patientsвЂ™ charts from the last six months. It may be necessary to include other variables associated with LOC and HbA1c independently, in order to establish any possible indirect effects of LOC over HbA1c. Acknowledgements: NIH/NIDDK T35 DK007431-26 (09012151), Center for Health Disparities Research Classification: Medical Student Type of Research Project: Clinical Science Email Address of Corresponding Author: stromjl@musc.edu Medical Student Poster #19 Effect Of Trust In Health Care Providers On Multiple Diabetes Outcomes Bouges Shenikqua, Lynch CP, Strom JL, Egede LE MUSC Department of Medicine, Division of General Internal Medicine and Geriatrics and the Ralph H. Johnson VAMC Diabetes is the seventh leading cause of death claiming the lives of 25.8 million Americans. This chronic disease increases the risk of macrovascular and microvascular complications and heart disease. In order to reduce the number of patients suffering from this high burden condition, a greater understanding of the obstacles hindering care to patients with diabetes is needed. Studies have shown a positive relationship between trust in primary care provider, patient adherence to medication and health related quality of life in patients with diabetes. In addition, a strong correlation has been shown between increased patient satisfaction in healthcare services and lowered glycated hemoglobin levels, better continuity of care and greater trust in the medical system. A sample of 534 patients with type 2 diabetes was recruited from three primary care clinics (an academic Internal Medicine clinic, a federally qualified health center, and a Veterans Affairs (VA) primary care clinic). Self-identified type 2 diabetic patients completed a survey about their personal characteristics, belief systems and preferences, health-related knowledge, behaviors and attitudes. The predictor variable, trust, was measured by a 17-item multidimensional trust in health care systems scale (MTHCSS) scored on a 5-point scale with a minimum score of seventeen and a maximum score of eighty-five. Higher scores indicate greater trust in the healthcare system. The primary outcome was glycemic control measured by glycosylated hemoglobin A1C (HbA1c). Mean scores of the trust index will be compared between older (в‰Ґ65 years of age) and younger (<65 years of age) individuals. When examining the mean differences in trust scores, individuals в‰Ґ65 years of age had significantly higher trust scores compared to those younger than 65 year old (p=0.0030). In addition, age had a significant impact on glycemic control (p=0.0019) and diastolic blood pressure (p=0.0000). Based on our preliminary results, trust was not a predictor of glycemic control. Age on the other hand did affect glycemic levels and diastolic blood pressure. Further studies are needed to determine why trust was not a predictor of glycemic control in this particular study when current literature shows different. Acknowledgements: NIH/NIDDK T35 DK007431-26 (09012151), Center for Health Disparities Research Classification: Medical Student Type of Research Project: Clinical Science Email Address of Corresponding Author: stromjl@musc.edu Medical Student Poster #20 В Connexin 40 Remodeling in Purkinje Cardiomyocytes Post-Myocardial Infarction Brown, Satara A. 1, Mary S. Rackley2,3, Brett S. Harris, PhD4, Terrence X. OвЂ™Brien, MD2,3 Medical University of South Carolina College of Medicine1, Gazes Cardiac Research Institute, Division of Cardiology, Medical University of South Carolina2 Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC3, Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina4 Introduction: Purkinje cardiomyocytes are specialized cardiomyoctes that connect to working cardiomyocytes to facilitate contraction of the heart muscle. Connexin 40 (Cx40) is the predominant connexin found in gap junctions of Purkinje cardiomyocytes; however, Cx43 and Cx45 are predominant in working cardiomyocytes. In working cardiomyocytes following myocardial infarction (MI), Cx43 remodeling occurs, which is indicated by lateralization of Cx43 and ensuing arrhythmias. We hypothesize that in murine Purkinje cardiomyocytes, MI will cause disorganization of Cx40 expression at gap junctions. Methods: A Cx40EGFP/+ transgenic mouse model post-surgical ligation of the left anterior descending artery was utilized to conduct this study. EGFP, enhanced green fluorescence protein, allowed identification of Purkinje cardiomyocytes. Antibodies to detect pan-cadherin and Cx40 were used in immunofluorescence staining of tissues. Immunofluorescence and confocal microscopy were employed to image gap junctions and intercalated disks in EGFP areas. Differences in Cx40 expression, cadherin expression, and colocalization of Cx40 and cadherin in control mice and mice that have experienced MI were quantified. Results: Cx40 remodeling was indicated by decreased Cx40 expression, decreased cadherin expression, and decreased colocalization of Cx40 and cadherin in the Purkinje cell areas. Cx40 expression decreased by 56%, cadherin expression decreased by 69%, and colocalization decreased by 24%. This indicated that gap junctions were deficient and relocated from their normal locations at intercalated disks following MI. Conclusion: These results parallel changes that have been detected with Cx43 expression in working cardiomyocytes. Alterations in Cx40 in Purkinje cells may be responsible for lifethreatening arrhythmias that can occur post-MI. These findings in the mouse model can be used to develop a treatment for post-MI arrhythmias in humans in the future. Medical Student В Poster #21 В Inhibiting Effect of Albumin on Biofilm Formation in Titanium Implants In vivo Desai, Shivam, College of Medicine Year 2 Basic Science Mentor: Qian Kang (kangqk@musc.edu), Department of Orthopaedic Surgery Bacterial infection is an extremely serious complication after orthopaedic surgeries namely because of the biofilm mode of growth of the infecting bacteria. Postoperative infections often require removing the implant altogether so more preventative measures are needed to inhibit bacterial adhesion. This study aimed to evaluate whether titanium surfaces coated with crosslinked albumin could reduce bacterial biofilm in vivo. Titanium discs were coated with bovine serum albumin cross-linked with carbodiimide. The discs were placed subcutaneously into 8 rats and challenged with S. aureus. 7 days after the infection, the discs were retrieved and evaluated using confocal fluorescent microscopy and dilution plate enumeration. The results show that the albumin coating disrupted and prevented strong bacterial biofilm formation. The discs covered with albumin displayed 80% fewer colony forming units. These results imply that implants coated with cross-liked albumin coating may offer viable prophylaxis to reduce infection in any implantation surgery. Medical Student В Poster #22 Multiple Cardiovascular Risk Factor Control (MCRFC) Across Sites of Care in Type 2 Diabetes DeWeerth, Jacob, Dismuke CE, Strom JL, Egede LE MUSC Department of Medicine, Division of General Internal Medicine and Geriatrics and the Ralph H. Johnson VAMC Background: Diabetes affects 8.3% of the US population. Glycemia (HbA1c), Lowdensity Lipoprotein (LDL) cholesterol and blood pressure (BP) control are the main cardiovascular risk factor targets for clinicians in managing diabetes. There is little evidence regarding the association of facility type with diabetes outcomes. We examined the association of facility type with single and a multiple measure of control of cardiovascular risk factors (MCRFC). Methods: 534 individuals with type 2 diabetes were recruited from a private hospital affiliated clinic (MUSC), a Federally Qualified Health Center (FQHC) and a VA facility. We created MCRFC which took the value of 1 if all three factors under control. We performed chi2 to examine socio-economic, separate risk factors and MCRFC by facility, We estimated the independent association of facility type with each risk factor and MCRFC, adjusting for covariates in logistic regression. Results: At FHQC, individuals were predominantly Black (84.83%), female (65.56%), 50-64 (52.81%), unmarried (70.06%), high-school graduates (43.75%), unemployed (72.30%), and uninsured (45.76%) with less than $10,000 income (54.34%). At VA, individuals were predominantly Black (51.88%), male (97.51%), 50-64 (46.47%), married (52.08%), some college (47.48%), unemployed (79.17%), government insured (75.00%), had $35,000 plus income. At MUSC, individuals were predominantly Black (65.13%), female (66.41%), 65 plus (42.15%), unmarried (59,5%), equally less than high school (30.23%) and high school (30.23%) educated, unemployed (75.38%), government insured (74.71%), had $35,000 plus income. In unadjusted analysis, at FQHC, 38.89% had BP, 51.63% LDL, 10.43% MCRFC control. At VA, 57.74% had BP, 74.15% LDL, 19.17% MCRFC control. At MUSC, 37.35% had BP, 64.37%, 7.34% MCRFC control. After adjustment, MUSC associated with 57% lower MCRFC (OR 0.428, 95% CI 0.187:0.978), male with 277% higher MCRFC, Black with 44% lower MCRFC. Conclusion: After adjusting for socio-economic factors, VA facilities are associated with better MCRFC in individuals with diabetes. Acknowledgements: NIH/NIDDK T35 DK007431-26 (09012151), Center for Health Disparities Research Classification: Medical Student Type of Research Project: Clinical Science Email Address of Corresponding Author: stromjl@musc.edu Medical Student Poster #23 Effect of Spirituality on Multiple Diabetes Outcomes Ezenekwe, Chisom, Hernandez-Tejada, MA, Strom JL, Egede LE MUSC Department of Medicine, Division of General Internal Medicine and Geriatrics and the Ralph H. Johnson VAMC Health care and disease management researchers have again turned attention to the connection between religiosity/spirituality (R/S) and health. One way R/S may moderate health outcomes is through increasing the likelihood of positive health behaviors in chronic diseases that are affected by behavior such as Type 2 diabetes (T2DM). However, the topic of increased pro-health behaviors directly or indirectly resulting from R/S and revealed by indicators for glycemic control remains unexamined. The present study identified patient glycemic control by optimal biomarker values for LDL cholesterol, hemoglobin A1C (HbA1C), body-mass index (BMI), pulse, and systolic and diastolic blood pressure. A sample of 683 participants with T2DM was recruited from the MUSC University Internal Medicine Clinic, VA Medical Center, and Fetter Health Center. A 6-item Daily Spiritual Experiences Scale was used. Indicators of glycemic control were extracted from subjectsвЂ™ medical records. 45% of patients were 50-64 years old, the majority of the participants (56%) were male, 66% were black, 60% were married, 35% completed High School and 34% had some college, 76% were unemployed, 35% earned less than $10,000 annually and 68% received public healthcare. Linear regression predicted the possible relationship between spirituality and glycemic control. R/S correlates with Diastolic Blood Pressure (beta = 0.25, 95% 0.11, 0.40), in the adjusted model, indicating higher spirituality was associated with lower Diastolic blood pressure. There were no relationships between R/S and other indicators of glycemic control. Future research should focus on which specific practices across faiths are responsible for decreasing diastolic blood pressure, which then might be appropriate targets of a treatment regimen for patients with T2DM. Acknowledgements: NIH/NIDDK T35 DK007431-26 (09012151), Center for Health Disparities Research Classification: Medical Student Type of Research Project: Clinical Science Email Address of Corresponding Author: stromjl@musc.edu Medical Student Poster #24 Effect Of Delayed Discounting On Multiple Diabetes Outcomes In Adults With Diabetes Fox, Adam, Dismuke CE, Strom JL, Egede LE MUSC Department of Medicine, Division of General Internal Medicine and Geriatrics and the Ralph H. Johnson VAMC Background: Diabetes affects 8.3% of the US population. Glycemia (HbA1c), Lowdensity Lipoprotein (LDL) cholesterol and blood pressure (BP) control are the main cardiovascular risk factor targets for clinicians in managing diabetes. . Delayed discounting (DD) is a measure of an individualвЂ™s impulsivity based on willingness to forgo benefits today to receive a higher amount in the future. It is being increasingly considered as a barrier to patient adherence. We examined the association of DD rates with BP, HbA1c and LDL. Methods 534 individuals with type 2 diabetes were recruited from MUSC a private hospital affiliated clinic, VA and the Franklin C. Fetter Federally Qualified Health Center (FQHC). We used the 1996 Kirby model of delayed discount rate to estimate an individualвЂ™s level of impulsivity on a scale of 1-9 with 1 representing the lowest impulsivity and 9 representing the highest impulsivity levels. We estimated Pearson correlations of DD and impulsivity with BP, HbA1c and LDL. We estimated independent association of DD with each diabetes outcome adjusting for covariates. Results: Our sample was predominantly Black (65.63%), 50-64 (44.85%), male (56.37%), unmarried (59.50%), unemployed (76.18%), government insured (66.52%), less than $10,000 income (35.37%) and better or same health status as previous 12 months (71.99%). Unadjusted correlation showed no association between DD, impulsivity and diabetes outcomes. Adjusted analyses showed that each additional point in DD rate was associated with 17.89 lower systolic (95% CI -33.73:-2.05) BP. In same model, Black was associated with 9.67 higher systolic BP relative to White, private insurance 7.07 lower, and government insurance 5.72 lower, relative to uninsured. VA was associated with 7.88 lower, and MUSC 5.76 lower systolic BP relative to FQHC. Conclusion: In adjusted models, DD rate is associated with lower systolic BP. DD rates may have implications for clinical management of BP in individuals with diabetes. Acknowledgements: NIH/NIDDK T35 DK007431-26 (09012151), Center for Health Disparities Research Classification: Medical Student Type of Research Project: Clinical Science Email Address of Corresponding Author: stromjl@musc.edu Medical Student Poster #25 В P21-Activated Kinases (PAKs) as Potential Targets of HIV Infection Hayes, Lauren1; Serguei Spitsin, PhD2; John Meshki, PhD2; Florin Tuluc, MD, PhD2; and Steven D Douglas, MD2,3 1 College of Medicine, Medical University of South Carolina, Charleston, SC, United States; 2Division of Allergy and Immunology, The Children's Hospital of Philadelphia Research Institute, Philadelphia, PA, United States; and 3Department of Pediatrics, University of Pennsylvania Medical School, Philadelphia, PA, United States. Background: Human Immunodeficiency Virus (HIV) is a virus that is transmitted through sexual contact and exposure to blood products, and leads to the development of AIDS. HIV/AIDS has caused devastating loss of life and is a widespread public health concern; there are intensive efforts toward creating treatments in the wake of new resistant HIV strains. The goal of this project was to examine the prospective HIV inhibitor, IPA3. HIV inhibitors act in several different mechanisms, and different classes of drugs are often combined as a part of highly active antiretroviral therapy (HAART). IPA3 functions by inhibiting a group of enzymes found in human cells, p21-activated kinases (PAKs). PAKs are involved with various cell functions, including proliferation and motility, and they are also involved with HIV infection of the cell. PAKs associate with Nef, an HIV protein, and this interaction leads to increased viral replication. By inhibiting PAKs, IPA should theoretically reduce HIV infection. Objective: To examine the efficiency of IPA3 as an HIV inhibitor. Design/Methods: Monocyte-derived macrophages (MDMs) and peripheral blood mononuclear cells (PBMCs) were first exposed to various concentrations of IPA3. Cells were then infected with HIV. For four of the patient samples, PBMCs were exposed to the IIIB strain of HIV, while one patient sample had PBMCs that were exposed to the BaL strain. All four of the patient MDM samples were exposed to the BaL strain of the virus. After a set incubation time, cells were collected and lysed. RNA was isolated and converted to cDNA, and real-time PCR was performed in order to quantify the presence of mRNA copies of the HIV gag gene. Results: HIV infectivity (GAPDH normalized GAG copies) as percentage of control PBMC MDM IIIB Strain BaL Strain BaL Strain Control 100.00 100.00 100.00 IPA3 1Вµm 91.56 57.28 53.99В±18.36* IPA3 2Вµm 143.67 37.15 --IPA3 3Вµm 116.01 --37.33В±15.83* IPA3 5Вµm 89.59 20.58 11.07В±2.89* IPA3 10Вµm 72.64 9.10 17.39В±18.98 Results are presented as average В±SD, (*) P<0.05 versus non-treated control Conclusions: IPA3 showed statistically significant inhibition (P<0.05) of HIV when MDMs were infected with the BaL strain. Though IPA3 did not show statistically significant inhibition of either strain of HIV in PBMCs, there was some moderate inhibition of the BaL strain in PBMCs. In conclusion, PAKs are potential drug targets for the inhibition of HIV replication, and PAK inhibitors such as IPA3 deserve further study. Type of research project: basic EвЂђmail address of the corresponding author: hayele@musc.eduВ Medical Student В Poster #26 В Bleeding in Autosomal Dominant Polycystic Kidney Disease Iyer, Arun, MUSC, Department of Medicine, Division of Nephrology, Medical Student iyer@musc.edu Mentors: P. Darwin Bell, Ph.D., Rachel Sturdivant, M.D., Ruth Campbell, M.D., Division of Nephrology Abstract: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disease characterized by multiple bilateral cystic kidneys. The precise etiology is unknown but is related to the genes pkd1 and pkd2. Recent observations from murine model studies have noted that PKD mice display profuse bleeding in comparison to non-PKD mice. In our study, we examined the coagulation characteristics of PKD and non-PKD mice and human subjects. Hemostatic profiles, as measured by standard bleeding times (prothrombin time, PT, and activated partial thromboplastin time, aPTT) and rotational thromboelastometry (ROTEM). Additionally, the patient model was controlled by basic measures of kidney function, estimated glomerular filtration rate (eGFR), to avoid patients in kidney failure. Comparison of these groups yielded results that were not statistically different due to a small sample size (n=6, mice and n=9, human); however, possible correlation is evident warranting further investigation. Additional studies are ongoing. The problem will continue to be investigated to determine if conclusion is accurate. Assay studies will likely be completed to determine if there are any specific factor and metabolic deficiencies. Medical Student В Poster #27 В Epidermal growth factor-induced activation of Na+/H+ exchanger in orpk cilia (+) and orpk cilia (-) renal cells from a mouse model of polycystic kidney disease involves different signaling mechanisms. Joyner, Alisha1, Tanjina Akter2, Mary G. Blanton3, Maria N. Garnovskaya3 and Sonya D. Coaxum3. College of Medicine1, Rheumatology and Immunology2, Nephrology3, Medical University of South Carolina, Charleston, SC. Epidermal growth factor (EGF) receptor has been implicated in the pathogenesis of polycystic kidney disease (PKD). We explored the effects of EGF in orpk cilia (-) collecting duct cell line, derived from a mouse model of PKD, and in control, orpk cilia (+) cell line, to determine signaling pathways activated by EGF. We measured changes in extracellular pH as a reflection of the Na+/H+ exchange (NHE) with a Cytosensor microphysiometer. Exposure to 10 ng/ml of EGF caused в‰Ґ20% increase in NHE activity in orpk cilia (+) cells and в‰Ґ30% increase in NHE activity in orpk cilia (-) cells. Stimulation of proton efflux by EGF was blocked in the presence of 5-(N-methyl-Nisobutyl) amilioride in orpk cilia (+) and cilia (-) cells; however, the effect was much greater in orpk cilia (-) cells suggesting that NHE-1 and/or NHE-2 are involved in EGFinduced signaling in these cells. Immunoprecipitation experiments showed that EGF induced complex formation between NHE-1 and CaM in both cell lines. However, EGF induced complex formation between Jak2 and CaM only in orpk cilia (-) cells but not in orpk cilia (+) cells. These results suggest that EGF induces NHE-1 activity in orpk cilia (-) cells by the following pathway: EGFГ† EGFRГ† Jak2 activation Г† CaM binding to NHE-1Г† conformational change of NHE-1Г† activation of NHE-1. A separate pathway exists for orpk cilia (+) cells: EGFГ† EGFRГ† CaM binding to NHE-1 (independent of Jak2) Г† conformational change of NHE-1Г† NHE-1 activation. Medical Student В Poster #28 The Role of Tissue Transglutaminase 2 in the Modulation of Polymorphonuclear Leukocyte Function Lebel, David P., Meghan K. Anderson, Titus A. Reaves COM 2nd Year student, Department of Regenerative Medicine and Cell Biology Polymorphnuclear leukocyte (PMN) migration toward the lumenal surface is a major inflammatory event involving mucosal surfaces. In particular, inflammatory bowel disease which collectively includes CrohnвЂ™s Disease and Ulcerative Colitis, presents as a series of inflammatory conditions that involves dysregulated PMN transmigration across the intestinal epithelium. While the etiology is unknown, patientsвЂ™ symptoms are more pronounced during such migration. Tissue Transglutaminase (TGM) 2 is an enzyme that catalyzes calcium-dependent crosslinks of amino groups and has been implicated in a variety of cellular functions that include; GTPase activity (affects PMN adhesion), cell growth and wound healing. Interestingly, antibodies to TGM 2 are present in patients with Celiac Disease (inflammation localized to the small intestine) and a majority of CrohnвЂ™s Disease patients also have Celiac Disease. Despite these observations, the role of TGM 2 in PMN activity has not been widely explored. Using immunofluorescence, we determined that TGM 2 has both an extracellular and intracellular deposition in PMN. Treatment of PMN with an inhibitor of TGM 2 appears to promote translocation of the leukocyte-specific integrin CD11b to the surface of PMN. Cellular adhesion studies show that antibodies to TGM 2 can inhibit PMN attachment to fibrinogen (ligand for CD11b) by nearly 50%. This result suggests that TGM 2 may have a role in CD11b-mediated activities. Transwell migration experiments also show that TGM 2 can inhibit fMLP-directed migration more than 50%. Bacterial formylated peptides (fMLP) promote PMN migration toward such peptides. The fMLP receptor is a G-protein coupled (7TM spanning) receptor that regulates the PMN response through an up-regulation of adhesion and migration (PMN) receptors. Using Flow Cytometry experiments, we determined that TGM 2 affects adhesion and migration by modulating the PMN-fMLP receptor. These data highlight TGM 2 as a potential target molecule in the treatment of mucosal inflammation that involves aberrant PMN transmigration. Email: lebeld@musc.edu Medical Student Poster #29 Glycemic Control In VA Clinical Sites Compared To Non VA Sites Among Adults With Type 2 Diabetes Lumpkin, Jeanne, Dismuke CE, Strom JL, Egede LE MUSC Department of Medicine, Division of General Internal Medicine and Geriatrics and the Ralph H. Johnson VAMC Background: Diabetes affects 8.3% of the US population. Glycemia (HbA1c) is the main outcome target for clinicians in managing diabetes. There is little evidence regarding the association of facility type with HbA1c levels. We examined the association of facility type with HbA1c level in a population of adults with type 2 diabetes. Methods: 534 individuals with type 2 diabetes were recruited from a private hospital affiliated clinic (MUSC), a Federally Qualified Health Center (FQHC) and a VA facility. We performed chi2 tests to examine socio-economic characteristics by facility. We examined the unadjusted association of HbA1c level with facility type, using one-way ANOVA and Bonferroni tests .We estimated the independent association of facility type with HbA1c levels using linear regression and adjusting for covariates. Results: At FHQC, individuals were predominantly Black (84.83%), female (65.56%), 50-64 (52.81%), unmarried (70.06%), high-school graduates (43.75%), unemployed (72.30%), and uninsured (45.76%) with less than $10,000 income (54.34%). At VA, individuals were predominantly Black (51.88%), male (97.51%), 50-64 (46.47%), married (52.08%), some college (47.48%), unemployed (79.17%), government insured (75.00%), had $35,000 plus income. At MUSC, individuals were predominantly Black (65.13%), female (66.41%), 65 plus (42.15%), unmarried (59,5%), equally less than high school (30.23%) and high school (30.23%) educated, unemployed (75.38%), government insured (74.71%), had $35,000 plus income. In unadjusted analysis, VA was associated with 0.799 lower HbA1c and MUSC with 0.767 lower HbA1c relative to the FQHC. After adjusting for all covariates, VA was associated with 0.519 lower HbA1c (95% CI 1.023:-0.016), MUSC was associated with 0.505 lower HbA1c (95% CI -0.935:-0.075) relative to the FQHC. Age 65 and older was associated with 0.657 lower HbA1c (95% CI -1.139:-0.174), government insured with 0.491 lower HbA1c (95% CI -0.955:-0.028). Conclusion: After adjusting for socio-economic factors, VA and private facility was associated with lower HbA1c levels relative to FQHC. Acknowledgements: NIH/NIDDK T35 DK007431-26 (09012151), Center for Health Disparities Research Classification: Medical Student Type of Research Project: Clinical Science Email Address of Corresponding Author: stromjl@musc.edu Medical Student Poster #30 В INCREASED RENAL INVOLVEMENT IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) PATIENTS WITH CHILDHOOD DISEASE ONSET Meyer, Anna Katrina 1, Elizabeth McKinney2, James C. Oates1, Gary S. Gilkeson1, Diane L. Kamen1 INSTITUTIONS (ALL): 1. Department of Medicine, Division of Rheumatology and Immunology, Medical University of South Carolina, Charleston, SC, United States. 2. School of Medicine, University of Virginia, Charlottesville, VA, United States. ABSTRACT BODY: Purpose of Study: The purpose of this study is to investigate the influence of age of SLE disease onset in the development of renal disease. Methods Used: We investigated the incidence of renal disease in SLE patients enrolled in our Lupus Clinic Database and compared patients with childhood SLE disease onset ( 18 years of age). The analysis also included dialysis, renal transplantation, and death. Proportions between groups were compared using PearsonвЂ™s Chi Square or FisherвЂ™s Exact as appropriate. A p-value of <0.05 was considered to be statistically significant. Summary of Results: Table 1 shows demographic, renal, and outcome data of the study patients, 18.8% of whom had childhood onset SLE (cSLE). The mean age of SLE onset was 29.8 +/- 13.1 years. We found a statistically significant increase in incidence of renal disease in cSLE compared to adulthood onset SLE (aSLE) patients (p<0.01). When comparing mortality rates, we found a statistically significant increase in the number of deaths among cSLE compared to aSLE patients (p<0.04) with age of death at 25.4 +/- 5.0 years in cSLE and 47.4 +/- 7.7 years in aSLE (p<0.01). Although the values did not reach statistical significance, a higher proportion of cSLE patients compared to aSLE required dialysis and had renal transplant. Conclusions: There is strong evidence that childhood onset SLE tends to be more severe than SLE occurring during adulthood. Data from our center concur with several studies and suggests that SLE patients whose initial disease onset occurred before adulthood are more likely to develop renal abnormalities and have more severe disease outcomes, including death. Total Patients N=319 Age of SLE onset +/- SD in years cSLE n=60 aSLE n=256 29.8 +/- 13.1 13.6 +/- 3.8 33.6 +/- 11.5 P-value (cSLE vs. aSLE) <0.01 SLE disease duration +/- SD in years 6.7 +/- 7.4 9.6 +/- 9.3 6.0 +/- 6.7 0.01 Renal disease (%) 177 (55.5) 45 (75.0) 132 (51.0) <0.01 Females (%) 292 (91.5) 55 (91.7) 237 (91.5) NS African American (%) 257 (80.6) 49 (81.7) 208 (80.3) NS Caucasians (%) 52 (16.3) 8 (13.3) 44 (17.0) NS Dialysis (%) 29 (9.1) 9 (15.0) 20 (7.7) NS Renal transplant (%) 14 (4.4) 4 (6.7) 10 (3.9) NS Deceased (%) 12 (3.8) 5 (8.3) 7 (2.7) 0.04 Medical Student Poster #31 В High Prevalence of Vitamin D Deficiency in Adult with Inflammatory Bowel Disease at the Medical University of South Carolina Patel, Ankit1, Diane Kamen2, Lawrence Comerford3 College of Medicine, Medical University of South Carolina (MUSC). Division of Rheumatology, MUSC. Division of Gastroenterology, MUSC. Introduction: Vitamin D deficiency is a common occurrence in patients suffering from inflammatory bowel disease (IBD). Although vitamin D has long been known to be essential for bone health and mineralization, recent studies have proposed that vitamin D plays an antiinflammatory role and may play a part in the pathogenesis of CrohnвЂ™s disease and ulcerative colitis. The aim of our study was to look at the prevalence of vitamin D deficiency in patients with IBD and determine if there are any predictors that strongly correlate with vitamin deficiency. Methods: Using the Enterprise Data Warehouse at MUSC, de-identified data on 490 patients 18 years or older, since 2006, who had a diagnosis code of either вЂњregional enteritisвЂќ (CrohnвЂ™s) or вЂњulcerative colitis unspecified AND a total 25-hydroxyvitamin D (25D) lab value were studied. The season (summer, winter, spring, fall) that the initial 25D lab was drawn was used, in addition to age, sex, and race. Because all information was de-identified, IRB approval was not needed. Stata v11 was used to perform t-tests comparing mean 25D levels and logistic regression models comparing deficient to sufficient patients, with p-values of <0.05 considered significant. Results: Of the 490 patients, 19.8% were African American and 78.0% Caucasian. 67.0% had a diagnosis code of CrohnвЂ™s, 19.8% with ulcerative colitis, plus 13.2% who had both codes listed. 25D was significantly lower in African Americans ( n=97, mean= 20.4 +/- 12.9 ng/mL) than Caucasians (n=382, mean=32.0 +/- 12.8 ng/mL, p=0.00). Those with a diagnostic code of CrohnвЂ™s also had significantly lower 25D levels (n=330, mean =28.3 +/- 13.8 ng/mL) than ulcerative colitis (n=97, mean=31.9 +/- 13.7 ng/mL, p=0.02). Those with 25D levels in the summer had a mean value of 30.5 +/- 13.7 ng/mL & winter 27.4 +/- 12.1. Using a cutoff value of 30ng/mL for 25D, logistical regression analysis showed that race, diagnostic code of CrohnвЂ™s, and season are all significant predictors for 25D deficiency. Furthermore, with a lower cutoff of 20 ng/mL, analysis shows that race and diagnostic code are significant predictors. Conclusion: Vitamin D deficiency is highly prevalent among IBD patients. Race, season and type of IBD are significant predictors of vitamin D insufficiency (25D < 30ng/ml), with African Americans with Crohn's being at the highest risk. This exploratory analysis utilizing the MUSC Clinical Data Warehouse provides support for pursuing a prospective study investigating the role of vitamin D deficiency in IBD. Medical Student В Poster #32 Ethnic Differences in Control of Multiple Diabetes Risk Outcomes Reid, Jameka, Lynch CP, Strom JL, Egede LE MUSC Department of Medicine, Division of General Internal Medicine and Geriatrics and the Ralph H. Johnson VAMC The leading cause of death in diabetes is cardiovascular disease (CVD), which is even higher among ethnic minorities. Hypertension and hyperlipidemia are each independent risk factors for CVD. With poor glycemic control, these risk factors have greater adverse consequences in minority groups. Thus, ethnic differences in control of multiple diabetes risk factor outcomes were examined. A cross-sectional study was performed among 524 people recruited from three clinics: MUSC primary care, Veterans Affairs primary care, and Fetter, a federally qualified health center. Data on the primary outcome, multiple risk factor control, were obtained from medical records; poor control defined as glycosylated hemoglobin, HbA1c в‰Ґ7%, blood pressure (BP) в‰Ґ130/80mmHg, and low-density lipoprotein (LDL) cholesterol в‰Ґ100mg/dL. The independent effect of ethnicity on risk factor control was analyzed with a multiple regression using STATA v11. Results showed significantly fewer elderly (в‰Ґ65 years) black participants (32.2%) than whites (53.5%). Other ethnic differences showed more blacks than whites were female (52.1% versus 27.5%), unmarried (66.1% versus 48.2%), not high school graduates (29.2% versus 13.5%), had no insurance (21.5% versus 11.0%), and had annual income <$10,000 (44.5% versus 16.8%). Blacks had significantly worse BP (61.2% versus 42.5%) and composite risk factor (90.0% versus 82.3%) control than whites (p<0.001 for both). After adjusting for demographics, logistic regression showed blacks had 55% lower odds (odds ratio, OR 0.45, 95% CI 0.30-0.67) of good BP control and 43% lower odds (OR 0.57, 95%CI 0.33-0.98) of good composite control than whites. The odds of poorer BP control were also shown among VA (OR 2.02) and Fetter participants (OR 1.66) compared to MUSC. Black participants had poorer control of multiple diabetes risk factor outcomes than whites. Findings suggest that ethnic minorities likely need more supportive efforts and culturally sensitive approaches to management of diabetes risk to reduce disparities in care. Acknowledgements: NIH/NIDDK T35 DK007431-26 (09012151), Center for Health Disparities Research Classification: Medical Student Type of Research Project: Clinical Science Email Address of Corresponding Author: stromjl@musc.edu Medical Student Poster #33 В Absence of Estrogen Receptor Alpha Reduces the Number and Function of Plasmacytoid Dendritic Cells in Lupus Prone Mice Scott, Jennifer1, Melissa Cunningham2,3, Osama Naga2, Gary Gilkeson2 ,3 1 College of Graduate Studies, Department of Microbiology & Immunology. Med. Univ. of South Carolina, Charleston, SC 2Division of Rheumatology & immunology, Department of Medicine. Med. Univ. of South Carolina, Charleston, SC 3Ralph H. Johnson VA Medical Center, Charleston, SC Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease that affects women at a 9:1 ratio compared to men. As a result of this female predominance, the role of estrogen and its receptors are under investigation. Previous work in our laboratory shows that estrogen receptor alpha (ERa) deficient lupus-prone mice have significantly increased survival and less renal disease compared to wild type lupus prone mice. The improvement occurs despite similar levels of renal immune complex deposition and autoantibody production in ERa deficient and wild type lupus prone mice. Since autoantibody production and immune complex deposition remain intact in ERa deficient lupus prone mice, we hypothesize that ERa deficiency improves SLE by reducing the innate immune systemвЂ™s ability to respond to this immune activation. To study the innate immune response this research focuses the role of the ERa in the plasmacytoid dendritic cell (pDC). pDCs are the bodyвЂ™s major producers of type I interferon, a key cytokine in the innate defense against viruses. In addition to type I interferonвЂ™s role in host defense, its serum levels are elevated in SLE and it can cause the dissolution of tolerance when given to healthy individuals. Our findings show a decrease in pDC levels in ERa deficient lupus prone mice compared to wild type lupus prone mice. pDCs account for 60% of total bone marrow derived dendritic cells in wild type lupus prone mice, but only 35% in the ERa deficient lupus prone mice. Additionally, the pDCs from ERО± deficient lupus prone mice produce decreased levels of type I IFN compared to wild type lupus prone mice. Given these findings, the next step will be determining the mechanism by which ERО± deficiency reduces plasmacytoid dendritic cell number and decreases type I interferon production. Type of Research: Basic Science Affiliation: Rheumatology E-mail: ScottJL@musc.edu Medical Student В Project #34 В Unanticipated Effects of Adenosine Agonists on Microtubule Density Simmons, Flora, College of Medicine; Grace Wallenborn, Division of Cardiolgy, Department of Medicine; George Cooper IV, Division of Cardiology, Department of Medicine Increased microtubule density is one factor in the impairment of contractility and growth in pathological hypertrophy. This increase in microtubule density is caused by MAP4, a microtubule associated protein, decoration along microtubules. This, in turn, hyperstabilizes microtubules, impairing the heartвЂ™s ability to compensate with contraction or growth. There is a pathway developed that leads to MAP4 decoration of microtubules, beginning with catecholamine induced activation of Pak1. Adenosine is an endogenous nucleoside that has antiadrenergic effects in the heart. Adenosine has recently been showed to decrease the catecholamine induced increase in microtubule density. This research looked at the three receptor agonists of adenosine, A1, A2A, and A3 to find which one is responsible for the cardioprotective effects, ie, decreasing в€†-tubulin and pPak1. Isolated feline cardiomyocytes were treated with isoproterenol, A1, A2A, and A3 for courses of 1, 4, 24, and 48 hours. It was found that A1 agonist in the presence of ОІ-adrenergic stimulation provided cardioprotection by decreasing в€†-tubulin and pPak1 after 4 hours. A1 agonist treatment on control cells actually behaved in a cardiotoxic manner, increasing в€†-tubulin and pPak1. A2A and A3 did not decrease в€†-tubulin or pPak1 by very much, leading us to believe that the three receptors act synergistically to provide cardioprotection. Affiliation: Medical Student Type of Project: Basic Science research E-Mail: simmonf@musc.edu Medical Student В Poster #35 В Imbalance in Histone Acetyl Transferase and Histone Deacetylase Activity During Hypertrophy Smith, Christopher, Mona S. Li, Olga Chernysh, Elizabeth S. Inks*, James C. Chou*, Santhosh K. Mani and Donald R. Menick. Gazes Cardiac Research Institute, Department of Medicine, Division of Cardiology, *Department of Pharmaceutical and Biomedical Sciences, MUSC, South Carolina. Abstract: The high rate of morbidity in patients with diastolic heart failure, along with the 62 million people in the US annually diagnosed with some form of cardiovascular disease emphasizes the need for alternative means of therapy to treat heart failure. Previous work has demonstrated that inhibition of histone deacetylase (HDAC) activity has protective properties and significantly decreases symptoms associated with pressure-overload induced hypertrophy. This suggests that the natural equilibrium at which histone acetyl transferase (HAT) and HDAC enzymes are maintained in healthy heart tissue could be shifted in diseased myocardium. However, no one has measured HAT or HDAC activities in the normal or hypertrophic heart. We hypothesize that the normal balance of enzymatic HAT/HDAC activity is disrupted under pathological hypertrophic conditions. To investigate, feline myocardium were subjected to Pulmonary Artery Banding (PAB) to cause pressure overload induced hypertrophy for periods of 2 weeks, 4 weeks, and 8 weeks, and then examined for HAT activity to support previous findings of HDAC activity. Results indicated a decrease in HAT activity after 2 weeks and even more pronounced decrease in the 4th week of pressure overload. HAT activity was still significantly decreased after 8 weeks of pressure overload, in comparison to the nonbanded feline myocardium. HAT and HDAC activity in isolated adult cardiomyocytes and cardiac fibroblast were much lower than what is seen in other cell types. These results indicate that there is a disruption in the normal balance of HAT/HDAC activity in pathological hypertrophy. Inhibition of HAT/HDAC enzyme activity may be a potential therapeutic target for the treatment of heart failure. Type of Project: Basic Science E-mail: smitcr@musc.edu Medical Student В Poster #36 Predictors of Adequate Health Literacy In a Diverse Primary Care Sample with Type 2 Diabetes Teuber, Julie, Bains SS, Strom JL, Egede LE MUSC Department of Medicine, Division of General Internal Medicine and Geriatrics and the Ralph H. Johnson VAMC Background: Diabetes disproportionately affects minorities and populations with lower levels of education and socioeconomic status. Among diabetics, inadequate health literacy is common and has been associated with poor disease knowledge and selfmanagement. The objective of our study was to determine the sociodemographic predictors of health literacy in a minority diabetic population. Methods: 674 type 2 diabetes patients were recruited from three medicine clinics. A validated survey and screener was used to assess sociodemographic characteristics and health literacy. Health literacy status was dichotomized into inadequate and adequate health literacy. Health literacy status was compared by demographics using chi-squared statistics. Logistic regression models were used determine independent predictors of health literacy. Results: 66% of the sample was African American, 39% were 65+ years, 24% had less than a high school education, and 75% percent of our sample had adequate health literacy. There were significant differences in health literacy by demographic characteristics. Among those with adequate literacy, it was higher among white race (Whites 80%, Blacks 72%; p<0.02), married status (78% married, 71% unmarried; p<0.05), higher education (92% college +, 60% < high school; p<0.001), those employed (89% employed, 70% unemployed; p<0.001), those insured (83% private insurance, 77% noninsured; p=0.02), and higher income (92% > $35,000, 64%<$10,000; p<0.001). In the logistic regression model, independent correlates of adequate health literacy were higher education (p=0.02), being employed (p=0.006), and higher income (p<0.001). Hispanic/other race was associated with inadequate health literacy (p0.03). Conclusions: In our sample, health literacy status varied by sociodemographic characteristics. Independent predictors of adequate health literacy included higher educational status, being employed, and higher income. Further research should be implemented to identify the mechanism by which these sociodemographic characteristics relate to health literacy in this population. Also, further studies should identify strategies to increase health literacy in minority groups at risk. Acknowledgements: NIH/NIDDK T35 DK007431-26 (09012151), Center for Health Disparities Research Classification: Medical Student Type of Research Project: Clinical Science Email Address of Corresponding Author: stromjl@musc.edu Medical Student Poster #37 Does Electrical Conduction Delay Progress with Time, Therefore, Increasing the Need for Resynchronization? Tuten, Neill, Medical Student, Robert Leman, MD, John Sturdivant, MD, Frank Cuoco, MD and J. Marcus Wharton, MD. Medical University of South Carolina, Charleston, SC Abstract: Introduction: The magnitude and response rate with cardiac resynchronization therapy (CRT) is dependent on QRS duration. Accordingly, temporal changes in QRS duration may affect CRT eligibility or response. To assess this possibility, we evaluated serial ECGs at a large Universitybased hospital. Methods: We conducted a review of ECGs showing sinus rhythm and QRS prolongation over a 6-year period. They were grouped into LBBB, RBBB, or IVCD by standard criteria. Patients with at least 2 ECG separated by > 12 months were analyzed. QRS measurements were determined by a computerized ECG system. Results: The database consisted of 6537 ECGs with LBBB, RBBB, or IVCD over a period of six years. There were 75 patients with LBBB, 117 patients with RBBB, and 51 patients with IVCD having serial measurements. Fourteen of the 75 patients with LBBB had a QRS width less than 130ms, with an average QRS change of -0.57ms (SD 12.2) over an average period of 38 months and an average baseline QRS of 124.3ms (SD 6.6). Forty-one of 117 patients with RBBB had a QRS width less than 130ms, with an average QRS change of 6.15ms (SD12.7) over an average period of 36 months and a baseline QRS of 120.3ms (SD 10.4). All patients with IVCD had a baseline QRS width less than 130ms (116.1ms SD 6.5, which changed 1.61ms SD 11.8 over an average time of 25 months). Conclusions: QRS duration changes little over a 3 year time period; therefore, it is unlikely that more progressive QRS prolongation will impact CRT eligibility or response. Author Disclosure Information: N. Tuten: None. R. Leman: None. J. Sturdivant: None. F. Cuoco: None. J. Wharton: None. Medical Student Poster #38 Gender Differences in Composite Control of Cardiovascular Risk Factors Winchester, Rhonda, Lynch CP, Strom JL, Egede LE MUSC Department of Medicine, Division of General Internal Medicine and Geriatrics and the Ralph H. Johnson VAMC Women with diabetes are at greater risk than men of developing cardiovascular disease (CVD) and worse outcomes. CVD risk factors are also less well-controlled in women than men. However, gender differences in composite control of these risk factors in diabetes are less clear; therefore, this study sought to understand this relationship. Data were collected from participants with type 2 diabetes at 3 primary care settings (MUSC University Internal Medicine, Franklin C. Fetter Family Health Center, Inc., a Federally Qualified Health Center, and the Ralph H. Johnson VAMC primary care clinic). Participants completed surveys to gather demographic data (personal characteristics, socioeconomic status, and self-rated health). Data for the outcome, composite risk factor control (glycosylated hemoglobin, HbA1c; blood pressure, BP; and low-density lipoprotein-cholesterol, LDL-C), were obtained from medical records. STATA v11 was used to analyze demographic differences by gender with chi-square tests and the independent effect of gender on composite control (odds ratio, OR, with 95% confidence interval, CI) with multiple regression. Of 534 participants, 56.3% were male (41.4% white, 55.8% black, 2.9% other) and 43.7% female (20.3% white, 78.4% black, 1.3% other). Significant gender differences showed that, compared to males, more females were <50 years old (12.3% versus 22.2%), not married (47.9% versus 74.4%), had less than high school education (18.2% versus 31.4%), and lower income (23.5% versus 50.3%). A higher proportion of males than females had good BP (в‰Ґ130/80mmHg), LDLC (<100mg/dL), and composite control (all p<0.001). In multivariate analyses adjusted for demographic variables, males had an OR of 1.70 (95%CI 1.17, 2.48) for good LDL control, OR 1.66 (95%CI 1.16-2.38) for good BP control, and OR 3.14 (95%CI 1.705.79) for good composite control than females. Findings demonstrate poorer composite risk factor control among women than men. This suggests that management of CVD risk in women with diabetes is inadequate. Therefore, more aggressive efforts should target women in attaining early risk factor control. Acknowledgements: NIH/NIDDK T35 DK007431-26 (09012151), Center for Health Disparities Research Classification: Medical Student Type of Research Project: Clinical Science Email Address of Corresponding Author: stromjl@musc.edu Medical Student Poster #39 Prevalence and Predictors of Sleep Disorders in an Adult Sample with Type 2 Diabetes Yazdy, G, Bains SS, Strom JL, Egede LE MUSC Department of Medicine, Division of General Internal Medicine and Geriatrics and the Ralph H. Johnson VAMC Objective: To determine the overall prevalence and sociodemographic predictors of sleep disorders in a diabetic population. Methods: Validated surveys were distributed at three clinics in Charleston, South Carolina. Data was obtained regarding sociodemographic factors and sleep disorders. 683 patients were recruited over a 10-week period. Sleep disorder questions assessed quality of sleep/rest. Logistic regression models were used to assess sociodemographic predictors of sleep disorders. Results: In our sample, 66% were white race, 85% were 50 years old or older, 56% were male, 60% were unmarried, 58% had < high school education, 76% were unemployed, 18% were uninsured, 35% had <$10,000 income, and 72% reported their health status as either better or the same as last year. Among the sleep disorders, 41% reported sleeping < 7 hours daily, 64% reported snoring, 65% reported unintentionally nodding off for at least 1 day a month, and 10% reported unintentionally nodding off while driving at least 1 day a month. In our logistic regression models, less than 7 hours sleep was less likely among those with poor health status (p<0.001) and participants at the VA site (p=0.006). Unintentionally nodding off was associated with black race (p=0.004) and unintentionally nodding off while driving was less likely among black (p=0.001) and Hispanic/other race (p=0.03) . No sociodemographic variables were significantly associated with snoring. Conclusions: OSA risk factors are prevalent in this population of patients with diabetes. The relationship between sociodemographic characteristics and varying sleep disorders need to be investigated to establish a possible mechanism by which they are linked. Acknowledgements: NIH/NIDDK T35 DK007431-26 (09012151), Center for Health Disparities Research Classification: Medical Student Type of Research Project: Clinical Science Email Address of Corresponding Author: stromjl@musc.edu Medical Student Poster # 40 В Using proteomics analysis to identify novel proteins in marrow niche microenvironment that contribute to the enhanced donor cell engraftment with plerixafor treatment. An, Ningfei1, Alison Bland2, John Lazarchick3, Zihai Li1,4, Andrew Kraft1, John Arthur2, and Yubin Kang1 1 Division of Hematology-oncology, 2Division of Nephrology, Department of Medicine, 3Department of Pathology and Laboratory Medicine, 4Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina Enhancing donor cell recovery is a very important goal in hematopoietic stem cell transplantation (HCT). Hematopoietic stem cell (HSC) reconstitution is regulated by marrow niche microenvironment that consists of cellular and non-cellular elements including cytokines, chemokines and many other soluble factors. We recently found that post transplant administration of plerixafor (a specific and reversible CXCR4 antagonist) selectively enhanced donor cell engraftment and promoted recovery of all donor cell lineages in a congeneic mouse transplant model (Kang et al, 2010, PLoS One 5, e11316). We hypothesized that plerixafor enhances donor cell reconstitution in part by modulating the levels and constitution of soluble factors in niche microenvironment. METHODS AND RESULTS: To test this hypothesis, we transplanted lethally irradiated C57Bl/6 mice with sorted c-Kit+ Lin- Sca-1+ HSCs and then injected s.c. PBS or plerixafor (5 mg/kg) every other day beginning at day +2 post transplant. At day +7 post transplant, the mice were sacrificed. Tibias and femurs were flushed with PBS and marrow supernatants collected. We found that the marrow supernatants from PBS treated- transplant mice inhibited bone marrow cell (BMC) colony forming units (CFUs). In contrast, the marrow supernatants from plerixafor treated- transplant mice significantly increased BMC CFUs. Plerixafor per se did not affect CFUs. We next used a multiplexed, mass spectrometry-based, quantitative isobaric tagging proteomics approach to compare the protein expression in marrow supernatant of PBS treated- transplant mice and that from plerixafor-treated transplant mice. We identified a total of 289 proteins, 3 of them only present in the marrow supernatants of PBS treated- transplant mice. Twenty-three proteins were increased (>2 fold) and 7 decreased in plerixafor treated- transplant mice. We then performed additional studies to validate our proteomics results. We focused on thioredoxin, one of the 23 proteins that increased in the marrow supernatant of plerixafor treated- transplant mice. Thioredoxin is a small oxidoreductase protein important in preserving tissue redox homeostasis, metabolic functions, and cellular integrity. We found that thioredoxin mRNA expression in BMCs was up-regulated in plerixafor treated- transplant mice. Furthermore, we found that thioredoxin increased BMC CFUs, enhanced the recovery of platelet counts in sublethally irradiated mice, and protected against radiation-related death. CONCLUSION: Our studies demonstrated that factors in the marrow niche microenvironment play a critical role in hematopoiesis. Measuring changes in proteins in marrow niche microenvironment will not only allow us to understand the mechanisms of action of plerixafor, but also provide clue on potential novel targets that can be used to further enhance hematopoiesis. First Author: Ningfei An, postdoctal, Type of research: basic science Corresponding Author: Yubin Kang Emial: kangy@musc.edu Postdoctoral Basic Science В Poster #41 Role of p38/Akt Signaling Pathway in the Regulation of Sodium/Calcium Exchanger Expression in Adult Cardiomyocytes Chernysh, Olga, Santhosh K. Mani and Donald R. Menick Department of Medicine, Division of Cardiology, Medical University of South Carolina, Charleston, SC Introduction: The sodium/calcium exchanger (NCX1) is regulated at the transcriptional level in cardiac hypertrophy and heart failure. Upregulation of NCX1 affects sarcoplasmic reticulum calcium loading and directly contributes to contractile dysfunction of failing myocardium. In animal models, it has been demonstrated that pharmacological inhibition of NCX1 may be beneficial in heart failure and during ischemia/reperfusion. However, most studies have focused only on the acute effects of NCX1 inhibitors on calcium homeostasis, and there is little information available on the potential risks and benefits of chronic therapeutic inhibition of NCX1. Previous work from our laboratory has shown that prolonged treatment with NCX1 inhibitor, KB-R7943 results in the upregulation of Ncx1 gene expression in both isolated adult cardiomyocytes and intact mouse hearts. This upregulation is mediated via the activation of p38 and formation of a NCX1-p38 complex. However, the signaling pathway leading to the increase in Ncx1 gene expression remains to be elucidated. Hypothesis: NCX1, whose activity is acutely sensitive to cytosolic calcium, sodium and membrane potential, can also regulate its own expression in an activity-dependent manner as part of a macromolecular signaling complex. Results: To identify potential downstream targets of p38, we treated isolated adult feline cardiomyocytes with KB-R7943 in the presence of p38 inhibitor, SB203580, which resulted in the inhibition of Akt kinase activation. Co-immunoprecipitation studies also showed that Akt was in complex with NCX1. Conclusion: Our results suggest that p38/Akt pathway plays a role in regulating Ncx1 gene expression in response to pharmacological inhibition of the exchanger. Type of Project: Basic Science E-mail: chernysh@musc.edu Postdoctoral Basic Science Poster #42 В Specific targeting of virus-infected cells through inhibition of sphingolipid biosynthesis Dai, Lu 1,2, Zhiqiang Qin1,2, Charles D. Smith3 and Chris Parsons1,2 Affiliations: Departments of Medicine1, Craniofacial Biology2, and Pharmaceutical & Biomedical Sciences3, Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas St., Charleston, SC 29425 Abstract: Generation of sphingosine-1-phosphate (S1P), through the enzymatic activity of sphingosine kinase isoforms 1 and 2 (SK1 and SK2), facilitates signal transduction associated with cell proliferation and survival. Furthermore, targeting of SK2 reduces cancer progression in animal models. Roles for SK and S1P in viral cancer pathogenesis have, however, not been explored. The KaposiвЂ™s sarcoma-associated herpesvirus (KSHV) is the causative agent of KaposiвЂ™s sarcoma (KS) and primary effusion lymphoma (PEL), tumors most often encountered in the setting of HIV/AIDS and organ transplantation. The most common therapeutic approach for these tumorsвЂ”conventional cytotoxic chemotherapyвЂ”is limited by its lack of efficacy and toxicities that compound those incurred by antiretroviral and immunosuppressive agents. We used a novel compound preferentially targeting SK2 (ABC294640) to determine whether SK2 regulates cellular pathogenesis following de novo KSHV infection of primary human endothelial cells (EC) and for patient-derived, KSHV-infected PEL cells. We found that targeting SK2 induced caspases-mediated apoptosis more readily for KSHV-infected EC and PEL cells relative to their respective KSHV-negative counterparts. Moreover, we identified two possible mechanisms for this effect: 1) preferential accumulation of pro-apoptotic ceramide species in KSHV-infected cells during SK2 inhibition; and 2) induction of KSHV вЂњlyticвЂќ genes associated with programmed cell death. Exploring potential mechanisms for these endpoints, we found that SK2 inhibition selectively suppresses expression of specific KSHV-encoded microRNAs (miRNAs) which activate anti-apoptotic signaling and which suppress KSHV lytic gene expression. Subsequent experiments revealed that SK2 inhibition suppressed KSHV-induced phosphorylation of signaling intermediates associated with cell survival, and ectopic expression of specific KSHV miRNAs during SK2 inhibition partially restored activation of these intermediates, reduced KSHV lytic gene expression, and restored viability for infected cells. Finally, using an established murine model for PEL, we found that ABC294640 significantly prolonged disease-free survival if given shortly after tumor initiation and dramatically reversed disease progression if given following establishment of PEL tumors in the model. Collectively, these data demonstrate a role for SK2 and S1P in the selective regulation of anti-apoptotic KSHV miRNAs and suggest that targeting SK2 offers a viable therapeutic strategy for KSHV-associated malignancies. Category: Postdoctoral Scholar (Lu Dai), Basic Science E-mail: parsonch@musc.edu Postdoctoral Basic Science В Poster #43 Global DNA Methylation and DNA Hydroxymethylation in Systemic Lupus Erythematosus (SLE) within the Gullah African American Population French, Kristen L.1,2, Anna K. Meyer1,3, Gary S. Gilkeson1, and Diane L. Kamen1 1 Division of Rheumatology and Immunology, Department of Medicine 2 Corresponding author (frenchkl@musc.edu), Postdoctoral Fellow, Basic Science 3 Medical Student, College of Medicine This epigenetic project is based in both clinical and basic sciences, with translational implications. SLE disproportionately affects females and African Americans, yet occurrence of SLE has not been satisfactorily explained by genetic, hormonal or socioeconomic factors. This has led to growing interest in epigenetic modifications such as DNA methylation, which has been shown to be decreased below normal levels (hypomethylation) in SLE patients. Interestingly, the demethylating agent 5-azacytidine is known to cause a reversible lupus-like syndrome in both humans and animal models. In addition, some normally silenced, methylation sensitive genes related to autoimmunity are found to be overexpressed in SLE patients. However, DNA methylation studies in SLE have not differentiated between the two DNA nucleic acids 5methylcytosine (5-meC) and 5-hydroxymethylcytosine (5-hmC). While 5-meC modifications silence gene expression, 5-hmC appears to promote conditions which lead to gene expression, similar to hypomethylation. We hypothesized that patients diagnosed with SLE would exhibit global decreases in 5-meC and global increases in 5-hmC in peripheral blood mononuclear cells (PBMCs) compared to controls. By focusing on the Gullah African American population, we hoped to limit genetic and environmental variability, due to the historical geographical isolation and low genetic admixture (with non-African descendents) of this population. Additionally, we hypothesized that levels of 5-meC and/or 5-hmC would correlate with biomarkers of immune dysregulation and autoimmunity in both patients and controls. ELISA-like assays with antibodies specific for 5-meC or 5-hmC were utilized in this study. Our preliminary results indicate that there is no significant difference in 5-meC or 5-hmC levels in the PBMCs between patients (n=45) and controls (n=45) or between controls who are positive (n=11) or negative (n=33) for antinuclear antibodies (ANA). We did observe a significant difference between females (n=80) and males (n=10) with females having lower levels of 5-meC (p<0.01) and 5hmC (p<0.05) compared to males. Levels of 5-meC and 5-hmC showed a moderate positive correlation to each other (r=0.56, p<0.001), contrary to our prediction of a negative correlation. The finding of no difference in 5-meC or 5-hmC levels between patients and controls may indicate that Gullah AAs have similar sensitivities to influences on DNA methylation or have had similar exposures due to their historical geographic isolation. The gender difference observed is intriguing and may be partially explained by the wider variability in 5-meC and 5hmC levels seen in males. Further analysis of more specific clinical biomarkers is currently underway. Support: SCTR Grant #1206 (NIH/NCRR Grant Number UL1RR029882); Training Grant in Inflammatory and Fibrosing Diseases (NIAMS T32 AR050958-07); and Environmental Determinants of Autoimmunity (NIH/NIEHS R21 ES017934). Postdoctoral Basic Science Poster #44 В Acquired Defects of Lupus Prone Mice-derived Mesenchymal Stem Cells Lead to Poor Effects of Autologous Transplantation in NZB/NZW F1 mice. Gu,Fei1,2, Ivan Molano1, Lin Yung Sun2 and Gary Gilkeson1,3. 1Division of Rheumatology & Immunology, Department of Medicine. Medical University of South Carolina, Charleston, SC , 2 Division of Rheumatology & Immunology, Drum Tower Hospital, Nanjing, China, 3Ralph H. Johnson VA Medical Center, Charleston, SC. Objectives: Lupus is a systemic autoimmune disease characterized by the production of autoantibodies and end organ damage from immune complex deposition. Mesenchymal stem cells (MSC) possess immunomodulatory properties and also participate in tissue repair. Defects in MSC function are reported in cells derived from lupus prone mice and lupus patients. Thus, a key question in the use of MSC in lupus is whether MSC from lupus donors are intrinsically defective and thus not suitable for autologous transplantation. Methods: NZB/NZW F1 mice were treated with a single intravenous injection of 1Г—106 C57BL/6J (B6) MSC (B6-MSC, allogeneic/normal MSC, n=8), young NZB/NZW F1 MSC (YBW-MSC, autologous/pre-lupus MSC, n=8), old NZB/NZW F1 MSC (OBW-MSC, autologous/post-lupus MSC, n=8), B6 fibroblasts (FB, n=7), or phosphate buffered saline (PBS, n=7) at 24 to 26 weeks of age after onset of disease. We monitored proteinuria and serum anti-ds DNA antibody levels every two weeks. All mice were sacrificed at 8 weeks after treatment. Splenocytes were stained with CD3,CD4 and CD19 to identify T cells and B cells, respectively. Kidney pathological slides were stained with haematoxylin and eosin (H&E) and scored in a blinded fashion. The average intensity of glomerular immune complex deposition in five independent fields of one kidney section per animal was quantitated. Results: The mice in all three MSC transplantated groups got 100% survival at 8 weeks after treatment. All three sources of MSC led to less proteinuria and significant differences between the three MSC transplantation groups and PBS group were observed at 8 weeks after treatment. However, neither source of MSC impacted serum anti-dsDNA antibody levels though there was a trend towards lower levels in B6-MSC group. We found the spleens weight in B6-MSC and YBW-MSC group were significantly less than those in the other three groups. All three sources of MSC-treated animals had marked reduced C3 deposits in glomeruli compared to controls. However, only B6-MSC and YBW-MSC, but not OBW-MSC led to statistically decreased intensity of glomerular IgG depositon. All three sources of MSC significantly decreased the occurrence of renal vasculitis and necrosis versus the controls. B6-MSC and YBW-MSC improved overall renal pathology significantly and B6-MSC also ameliorated interstitial inflammation in kidneys. In addition, B6-MSC and YBW-MSC significantly reduced the absolute number of spleen CD4+ T cells and CD19+ B cells. We also found all three sources of MSC suppress T-cell proliferation in vitro potently but OBW-MSC did not work as well as B6MSC and YBW-MSC. Conclusion: These results indicate MSC transplantation after onset of disease does impact lupuslike disease in NZB/NZW F1 mice through mechanisms including suppression of T-cell and Bcell proliferation and suggest that allogeneic sources of MSC may be preferred to autologous sources, but the functional defects of lupus-MSC are not intrinsic, but acquired. Type of Project: basic science Postdoctoral Basic Science В Poster #45 Effect of Perceived Control on Quality of Life in Indigent Adults with Type 2 Diabetes Hernandez-Tejada Melba, Strom JL, Lynch CP, & Egede LE MUSC Department of Medicine, Division of General Internal Medicine and Geriatrics & Ralph H. Johnson VAMC Patients with type 2 diabetes mellitus (T2DM) report higher quality of life(QOL) when adequate glycemic control is achieved. However, it is uncertain whether control per se, or perception of control is most predictive of increased quality of life. To address this, we evaluated perceived control of diabetes and QOL in 188 patients from a low income clinic located at an academic medical center. QOL was assessed with the Medical Outcomes SF12. We computed physical and mental component scores. Perceived control was measured with a 15-item Perceived Control Questionnaire. Correlational analyses indicated a positive relationship between perceived control and both physical and mental QOL (r=0.53 and r=0.34 p<0.001, respectively). Linear regression analyses, in which related factors were controlled, supported this finding, with the first model accounting for 29.1% of the variance, and when controlling for demographics and comorbidity, 33.8% of the variance in the final model. Thus, increasing perceived control, perhaps by a combination of education and skills building (i.e., self-efficacy), may result in higher perceived QOL for patients with T2DM. Acknowledgements: Agency for Health Care Research and Quality 5K08HS11418, Center for Health Disparities Research Classification: Post Doctoral Fellow Type of Research Project: Clinical Science Email Address of Corresponding Author: hernanma@musc.edu Postdoctoral Basic Science Poster #46 TLR4 Activation Triggers a Robust Inflammatory Response and Interaction with Mononuclear Cells by Microvascular Endothelial Cells Lu, Zhongyang, Yanchun Li, Junfei Jin, Xiaoming Zhang, Maria F. Lopes-Virella, Yan Huang Division of Endocrinology, Diabetes and Medical Genetics, Department of Medicine Although coronary artery disease is a macrovascular disease, microvessels are developed inside atherosclerotic plaques and contribute to plaque inflammation and intraplaque hemorrhage. As the major cells in vessels, both macrovascular endothelial cells (MAC ECs) and microvascular endothelial cells (MIC ECs) contribute to atherosclerosis. However, the responsiveness of these cells to the activation of toll-like receptor (TLR)4, an innate immune receptor, has not been well characterized and compared. In this study, we showed that TLR4 activation by lipopolysaccharide (LPS) stimulated a much higher expression of inflammatory genes including cytokines, chemokines, growth factors and adhesion molecules in MIC ECs when compared to those in MAC ECs. Furthermore, TLR4 activation in MIC ECs, but not MAC ECs, led to an interaction with U937 mononuclear cells through MIC EC-released IL-6 to upregulate matrix metalloproteinase (MMP)-1 expression in U937 cells. To explore the mechanisms underlying the different responses to TLR4 activation by MIC and MAC ECs, we found that MIC ECs had higher expression levels of TLR4, MD-2 and CD14, and higher TLR4-mediated NFKB transcriptional activity than MAC ECs. Taken together, this study showed that TLR4 activation triggers a robust inflammatory response in MIC ECs. Given the essential role of inflammatory cytokines and MMPs in plaque destabilization in advanced atherosclerotic lesions, our study indicates that MIC ECs may contribute to plaque vulnerability through a TLR4-dependent mechanism. Dr. Zhongyang Lu, Postdoctoral Research Fellow Type of Research: Basic Science Corresponding author: Dr. Yan Huang (email: huangyan@musc.edu) Postdoctoral Basic Science Poster #47 В Proteomic analysis of cerebral spinal fluid reveals candidate biomarkers of domoic acid toxicosis in California sea lions Neely, Benjamin A.1, Jennifer Soper2, Frances M. D. Gulland2, John M. Arthur1,3, Michael G. Janech1,3 1 Department of Medicine, Division of Nephrology, Medical University of South Carolina, Charleston, SC 2 The Marine Mammal Center, Sausalito, CA 3 Research Service, Ralph H. Johnson VA Medical Center, Charleston, SC Domoic acid toxicosis (DAT) is a major cause of California sea lion (Zalophus californianus) strandings along the west coast of the United States. Domoic acid is a potent neurotoxin produced by some marine diatoms, which causes hippocampal atrophy and necrosis as a result of excessive stimulation of AMPA-kainate and NMDA receptors, and is rapidly cleared from the body. DAT is classified as acute or chronic, with the former recovering over time and the latter progressing to status epilepticus. Currently markers of DAT are limited and inconclusive; therefore by developing markers of DAT, diagnosis and treatment could be greatly facilitated. For this reason we evaluated whether protein differences exist in the cerebral spinal fluid (CSF) that could be utilized as markers of DAT. CSF samples from 11 sea lions [3 without DAT, 2 diagnosed with acute-DAT and 6 with chronic-DAT] were acquired from The Marine Mammal Center and proteins were digested with trypsin for analysis by tandem mass spectrometry. Data were searched using Mascot against a mammalian database, with identifications supported by Scaffold. We identified 182 experiment-wide proteins with a protein false discovery rate of <0.1%. Relative protein abundance was estimated for comparison by spectral counts across all samples and differences were detected using a Wilcoxon rank-sum test. Six proteins were significantly different (p<0.05) between non-DAT and DAT animals, five of which were higher in animals with DAT. Interestingly, Dickkopf-3 and Gelsolin were elevated in sea lions with DAT. Both of these proteins have been implicated in the progression of AlzheimerвЂ™s disease, suggesting that DAT and AlzheimerвЂ™s may share common features. Future studies to qualify these proteins as markers of DAT are ongoing. Postdoctoral Basic Science В Poster #48 В Diabetes accelerates cystogenesis and results in glomerular and tubular damage in a mouse model of polycystic kidney disease Sas, Kelli M.1 and P. Darwin Bell1,2. 1 Nephrology, Department of Medicine, Medical University of South Carolina, Charleston, SC; 2 Ralph H. Johnson VA Medical Center, Charleston, SC. The rate of progression in polycystic kidney disease (PKD) is highly variable and poorly understood. It is believed that additional, non-genetic factors such as environmental influences and pathophysiological conditions can influence the rate of cyst formation and disease progression. Diabetes (hyperglycemia) results in structural and functional hypertrophy in the kidney. We have previously found that renal hypertrophy accelerates cystogenesis. The goal of this study was to determine if the presence of diabetes would modify the time course and degree of renal cyst formation in a mouse model of PKD in which cilia are depleted. To examine the role of diabetes on cyst formation, we utilized a conditional floxed allele for the ift88/Tg737 gene to produce cilia (+) or cilia (-) adult mice. Mice were administered streptozotocin at 50 mg/kg for 5 days to induce diabetes. Blood glucose concentrations were elevated but not significantly different between groups. After 6 weeks, mice underwent MRI to determine cystic burden and kidneys were removed after 6 weeks or 3 months for histological analysis and electron microscopy. MRI and histological analyses identified accelerated cystogenesis mainly in the glomeruli and collecting ducts of diabetic cilia (-) mice. Additionally, diabetic cilia (-) mice exhibited abnormalities in non-cystic regions with signs of tubular stress and glomerular disease, as evidenced by primitive renal tubules, mesangial cell expansion, and fusion of glomerular foot processes. These abnormalities did not occur in cilia (+) mice. There was also a marked increase in lymphocytic infiltration and enhanced AKT, mTOR, Wnt, and EMT signaling in kidneys from the diabetic cilia (-) mice. Diabetes may be a significant risk factor for accelerated cyst formation and renal failure in PKD, and cilia may be reno-protective in diabetes. *Kelli M. Sas is a post-doc in basic science research. Corresponding author email: bellpd@musc.edu. Postdoctoral Basic Science В Poster #49 Association between Spirituality and Depression in Adults with Type 2 Diabetes Strom, Joni, Lynch CP, Hernandez-Tejada MA, & Egede LE Department of Medicine, Division of General Internal Medicine and Geriatrics & Ralph H. Johnson VAMC Purpose: Comorbid depression complicates glycemic control in patients with diabetes. Potentially protective factors have received little attention. This study examines the association between spirituality and depression among patients with type 2 diabetes. Methods: This prospective study included 201 adult participants with diabetes from an indigent clinic of an academic medical center. Participants completed validated surveys on spirituality and depression. The Daily Spiritual Experience Scale (DSES) measured a personвЂ™s perception of the transcendent (God, the divine) in daily life. The Center for Epidemiologic Studies-Depression scale assessed depression. Linear regression analyses examined the association of spirituality as the predictor with depression as the outcome, adjusted for confounding variables. Results: Greater spirituality was reported among females, non-Hispanic blacks (NHB), those with lower educational levels, and those with lower income. The unadjusted regression model showed greater spirituality was associated with less depression. This association was mildly diminished but still significant in the final model. Depression scores also increased (greater depression risk) with females and those who were unemployed but decreased with older age and NHB race/ethnicity. Conclusions: Treatment of depression symptoms may be facilitated by incorporating the spiritual values and beliefs of patients with diabetes. Therefore, faith-based diabetes education is likely to improve self-care behaviors and glycemic control. Acknowledgements: Agency for Health Care Research and Quality 5K08HS11418, Center for Health Disparities Research Classification: Post Doctoral Fellow Type of Research Project: Clinical Science Email Address of Corresponding Author: stromjl@musc.edu Postdoctoral Basic Science Poster #50 В IRS-1/2 Mediated Regulation of Hepatic OGT and OGA Expression Sundararaj, Kamala1&2, Abdelmohsen M Alqalam2, Katherine A Robinson2, Maria G Buse2, Lauren E Ball1. 1 Pharmacology, 2Medicine/Endocrinology, Medical University of South Carolina, Charleston, SC To investigate the role of hepatic insulin signaling in the postprandial regulation of O-GlcNAc transferase (OGT) and OGlcNAcase (OGA) expression, C57BL/6 male mice with a conditional knock out of IRS-1/2 in liver (LKO) were fed a chow or high fat diet (HFD) for 16 weeks and then either fasted for 18 hrs or fasted and refed ad libitum for 4 hrs. In control animals that were fasted or refed, qRT-PCR revealed a postprandial increase in OGT expression (146% В± 12.8, n=5) and a reduction in OGA transcript levels (65.7% В± 6.1, n=5). High fat feeding attenuated both the postprandial rise in hepatic OGT expression (123% В± 5.0, n=5) and the suppression of OGA expression (77.2% В± 4.6, n=5). In LKO mice in the refed state, OGT mRNA expression was reduced by 68% В± 1.5 (n=6) after 16 weeks HFD as compared to animals fed a chow diet. Furthermore with 16 weeks HFD, an elevation in the expression of OGA was observed in hepatic (170% В± 7.5) and adipose (316.5% В± 21.6, n=6) tissue as compared to chow diet. These studies reveal that the postprandial changes in hepatic expression of OGA and OGT are regulated, in part, by IRS-1/2 mediated insulin signaling in vivo and that the suppression of OGA expression in fat fed animals is lost in the absence of hepatic IRS-1/2. Supported by T32 HL07260 and RO1DK002001. Postdoctoral Basic Science В Poster #51 В Site specific phosphorylation of cardiac MAP4 reduces MAP4-microtubule binding and prevents deleterious effects of left ventricular pressure overload. Wallenborn, J. Grace1, Kasiganesan H1, Baicu C1, Harris BS2, Cheng GM1, Menick DR1, Cooper G1. 1 Department of Medicine, Division of Cardiology 2 Department of Regenerative Medicine and Cell Biology In severe pressure overload-induced cardiac hypertrophy, a dense microtubule network is formed in cardiomyocytes which is one cause of contractile dysfunction. This densification is the result of transcriptional upregulation of MAP4, the major cardiac microtubule binding and stabilizing protein, as well as increased MAP4-microtubule affinity. This increased affinity is driven by site-specific dephosphorylation of MAP4 at several serine residues, including serine 924, located in the microtubule binding domain of MAP4. Adenoviral mediated overexpression of mutant MAP4 mimicking constitutive phosphorylation at serine 924 leads to decreased microtubule network density. We hypothesized that in vivo, constitutive phosphorylation of cardiomyocyte MAP4 at serine 924 would ameliorate pressure overload-induced contractile dysfunction. To address this, site directed mutagenesis of MAP4 cDNA was used to switch serine 924 to aspartic acid (MAP4-S924D). This cDNA was cloned into the О±-myosin heavy chain promoter, and used to create a new transgenic mouse with cardiac restricted overexpression of MAP4-S924D. Left ventricular pressure overload (LVPO) was produced by transverse aortic constriction in male and female mice, 10-12 weeks old. Following 4 weeks of LVPO, LV structure and contractile function was characterized via echocardiography. Cardiomyocytes were isolated, and contractile function was measured in terms of sarcomere mechanics. In wild type mice, LVPO induced an increase in LV mass (128mg to 269mg), decrease in ejection fraction (50% to 19%), and decrease in fractional shortening (25% to 9%). Much lesser changes were seen in banded transgenic mice; LV mass was only marginally increased (112mg to 130mg), ejection fraction only decreased 51% to 46%, and fractional shortening from 26% to 23%. Isolated cardiomyocytes from WT mice had shorter resting sarcomere length, extent of shortening, shortening and relaxation velocity compared to transgenic mice. Overall, our results suggest that constitutive phosphorylation of serine 924 of cardiomyocyte MAP4 leads to a less deleterious response to pressure overload. Postdoc, Basic Sciences Corresponding author email: wallenbo@musc.edu Postdoctoral Basic Science В Poster #52 Growth factor plus preemptive plerixafor successfully mobilizes hematopoietic stem cells (HSC) in all multiple myeloma patients despite prior lenalidomide exposure. Abbas, MD, Jonathan A., Kristine McDonald, MD, Cindy Kramer, Kathy Hogan, Colleen Butcher, Amanda Littleton, Katie Shoptaw, YUbin Kang, MD, Robert K. Stuart, MD, Luciano J. Costa, MD/PhD Division of Hematology/Oncology, Department of Medicine OBJECTIVE. Lenalidomide, a component of several modern induction regimens in multiple myeloma (MM), is associated with suboptimal autologous hematopoietic stem cell (AHSC) mobilization. Cyclophosphamide plus filgrastim mobilization at least partially overcomes the negative impact of lenalidomide but leads to higher cost and toxicity. We hypothesized that growth factor plus preemptive plerixafor is a safe and highly efficient strategy for initial AHSC mobilization in MM despite prior exposure to lenalidomide. METHODS. We retrospectively reviewed patient characteristics and mobilization outcomes of 89 consecutive MM patients undergoing first mobilization with filgrastim or pegfilgrastim +/preemptive plerixafor using a previously validated algorithm based on day 4 peripheral blood CD34+ cell count (PB-CD34+) and mobilization target. Mobilization outcomes were analyzed for three distinct groups according to the extent of prior exposure to lenalidomide: no prior exposure (group A, N=40), 1 to 4 cycles (group B, N=30) and > 4 cycles (group C, N=19). RESULTS. Median age was 57.5 years and similar across groups. Multivariate analysis with PBCD34+ as the dependent variable yielded only age, number of prior cycles of lenalidomide and mobilization with pegfilgrastim as significantly associated with PB-CD34+. Only 45% of patients in A required plerixafor vs. 63% in B and 84% in C ,P=0.01. The median yield of CD34+ collected was 8.1 x 10^6 CD34+/kg in A, 7.4 x 10^6 CD34+/kg in B and 7 x 10^6 CD34+/kg in C. A higher proportion of patients in A (100%) met the mobilization target (6 x 10^6 CD34+/kg for most patients) than in B (90%) or C (79%), P=0.008. All patients collect at least 2 x 10^6 CD34+/kg. HSC collection was completed after a median of 1.5 daily apheresis sessions in A and B and 2 in C. The estimated cost of mobilization and collection was similar between A (median US$ 22,280) and B (US$ 22,280), but substantially higher in C (US$ 35,020). CONCLUSION. Steady state growth factor mobilization with a validated algorithm for preemptive use of plerixafor is an adequate upfront mobilization strategy for MM patients regardless of prior exposure to lenalidomide, negating the need for chemotherapy mobilization. Project Type: Clinical Research Project Lead Author Contact Information: abbas@musc.edu Clinical Fellow Poster #53 В REVISITED IMPACT OF HUMAN LEUKOCYTE ANTIGEN-DR MATCH IN KIDNEY TRANSPLANT RECIPIENTS Ahmed, Vaqar1 (Fellow Clinical Nephrology), Maria Francesca Egidi1, Bethany Jacobs Wolf2 1. Transplant Nephrology, 2. Division of Biostatistics & Epidemiology. Medical University of South Carolina. BODY: Purpose of Study: HLA-DR has been associated with poor long-term graft function. However, the impact of HLA-DR remains unclear under new immunosuppressive agents. We analyze graft outcomes in kidney transplant recipients with 1 and/or 2 HLA-DR mismatches compared to 0 HLA-DR mismatches. Methods Used: We reviewed 555 patients who received kidney transplants between January 2005 and June 2008. Kaplan-Meier survival analyses were used to examine associations between graft failure and different variables using a log-rank test to test for differences between groups. We developed a Cox regression model to determine graft survival by HLA-DR status adjusted for demographic and clinical characteristics. A two-tailed P value <0.05 was considered to be statistically significant. Summary of Results: Graft survival was lower in HLA-DR 2MM relative to HLA-DR 0MM (p=0.025). Subjects who received IL-2 antibody induction had significantly increased hazard of graft failure with 2 HLA-DR MM relative to those with 0 HLA-DR MM (95% CI for the hazard ratio (HR) 1.38-24.6, p=0.016). However, 0 HLA-DR MM was not associated with increased graft survival compared to 2 HLA-DR MM in patients who received induction with ALA (p=0.646). There was no significant effect of either CYA or FK on graft failure (p=0.295). However there was significantly increased hazard of graft failure for 2 HLA-DR mismatches relative to 0 mismatches (p=0.041) in both groups. Conclusions: Despite strong immunosuppression, HLA-DR mismatch has an adverse impact on long-term graft survival particularly in subjects who receive IL-2 induction. We conclude from this data that patients with HLA-DR mismatch may benefit from ALA induction. Type of research: Clinical Email address: ahmedv@musc.edu Clinical Fellow В Poster #54 В The Impact of Lobar Perfusion on Exercise Response to Endobronchial Valve Therapy in Advanced Pulmonary Emphysema Argula, Rahul G *, Charlie Strange*, Viswanathan Ramakrishnan+ * Division of Pulmonary & Critical Care Medicine, + Division of Epidemiology & Biostatistics Medical University of South Carolina, Charleston, South Carolina Background: Advanced heterogeneous pulmonary emphysema with hyperinflation impacts exercise tolerance in COPD. We evaluated whether baseline perfusion to the target lobe of patients receiving ZephyrВ® endobronchial valves (EBV) was associated with an improvement in 6 minute walk test distance (6MWTD). Methods: We performed a retrospective analysis on the treatment group of the VENT trial (N Engl J Med 2010; 363:1233) to evaluate the impact of baseline perfusion, measured by 99mTcMAA perfusion scintigraphy, on six-month improvement in 6MWTD. A mixed model analysis (SAS, Cary, NC) was performed for the treatment outcome adjusting for other variables such as age, fissure integrity, BMI, gender, heterogeneity score, destruction score, and lobar exclusion. Results: Of the 220 patients who received EBV therapy, 193 had complete perfusion scintigraphy data available. Dichotomized at the median, 99 had a low baseline target lobe perfusion and 94 had high target lobe perfusion. Among EBV patients with complete lobar exclusion at follow-up, a low baseline target lobe perfusion was associated with a significant improvement in 6MWTD when compared to a high baseline target lobe perfusion (30.24 Vs. 3.72 meters, p = 0.03). This effect persisted after controlling for target lobe destruction and heterogeneity scores. Correlations between the target lobe perfusion, destruction score and ipsilateral heterogeneity were small (R2 = 0.15 and 0.13 respectively, p<0.0001). The mixed model analysis also suggested interactions with gender. Conclusions: Patients having heterogeneous emphysema with a low baseline target lobe perfusion benefit from EBV therapy, with limited impact from the degree of target lobe destruction and heterogeneity. This effect is attenuated if the valves are not occlusive. Characterization of baseline perfusion may enhance clinical results of emphysema patients undergoing EBV therapy Author designation: Clinical fellow, Division of Pulmonary & Critical Care Medicine, MUSC. E-mail: argula@musc.edu Type of research: Clinical Clinical Fellow В Poster #55 В Endoscopic Resection of Duodenal Bulb Carcinoids: A Comparison of Rates of Complete Resection among the Suck-and-Ligate, Inject-and-Snare, and Snare-Alone Techniques Baltz MD, Joseph 1, Jim Madory DO2, Joseph Romagnuolo MD, MSc1, Robert Hawes MD1, and Brenda Hoffman MD1 1 MUSC Department of Medicine, Division of Gastroenterology & Hepatology, Charleston, SC 2 MUSC Department of Pathology and Laboratory Medicine, Charleston, SC Purpose: Endoscopic mucosal resection (EMR) is typically reserved for mucosal lesions, but mixed mucosal/submucosal tumors such as carcinoids are resectable without special techniques like submucosal dissection. The suck-and-ligate technique is used mostly in the esophagus and stomach rather than the duodenum for fear of perforation risk. The purpose of this study is to evaluate the adequacy of resection and complications of different endoscopic resection techniques of carcinoid tumors in the duodenal bulb. Methods: The medical records of patients in whom carcinoid tumors were endoscopically resected from the duodenal bulb from the year 2000 to 2010 were retrospectively reviewed. Patient demographics, endoscopic ultrasound (EUS) evaluation, type of resection technique, adequacy of resection (from pathology reports), specimen sizes, and complications were recorded. The Paris Classification was determined by photographs or by description of the lesions. Resection techniques included suck-andligate, inject-and-snare, and snare-alone. Statistical comparisons of proportions were performed using Fisher exact test. Results: A total of 30 consecutive cases of endoscopic resection were included. Please see the table below for complete results and analysis. 3 of 13 lesions in which the suck-and-ligate technique was used had positive margins. 4 lesions were Paris class IIa (flat, elevated lesions). 7 of 11 lesions in which the injectand-snare technique was used had positive margins. 1 lesion was Paris class IIa. 4 of 6 lesions in which the snare was used alone had positive margins. 1 lesion was Paris class IIa. No complication was noted in any patient. The average specimen size was similar among the three groups. The differences among the three techniques in their rate of positive margins did not reach statistical significance. Total Procedures Positive Margins (%) Specimen Avg. Size (range) Number of IIa Lesions (%) Fisher exact (p Value) margin negative Fisher exact (p Value) Paris class Suck-and-Ligate 13 3 (23%) 7.5mm (3-13mm) 4 (31%) ------- Inject-and-Snare 11 7 (64%) 7.8mm (5-12mm) 1 (9%) p = 0.095 p = 0.37 Snare Alone 6 4 (67%) 7.2mm (4-13mm) 17 (%) p = 0.13 p = 1.0 Conclusions: EMR is an effective way to remove mixed mucosal/submucosal lesions, such as carcinoid tumors, in the duodenal bulb with a high rate of negative margins. The suck-and-ligate technique is as safe as and had a non-significant trend towards a higher percentage of complete resection than either of the other techniques. There is likely selection bias as certain morphologies may preferentially have been removed by one technique vs. another. It is not clear whether positive margins described by pathology were due to simple extension of lesion margin to the cautery line versus truly due to residual tissue incompletely resected as follow up data is not available at this time. Clinical Fellow В Poster #56 The Impact of Adult CF Programs on Adult Achievement Barto MD, Tara Lynn, 1, Patrick A. Flume, MD 1. 1 Division of Pulmonary and Critical Care Medicine, Medical University of South Carolina, Charleston, SC, USA. Introduction: CF patients are living longer and there is a growing adult population. We have established adult programs to provide age-appropriate care to this growing population. Transition programs are recommended to prepare patients not only for the movement from pediatric to adult health care but also to provide tools necessary for adult development. We would anticipate with implementation of these programs there would be a subsequent increase in achievement of adult milestones. Methods: We analyzed the CFF Patient Registry (CFFPR) comparing patients aged 2530 years in 1999 and 2008. In 2000, the CFF mandated there be adult care programs at each CF center, therefore patients were analyzed prior to and after this mandate. We evaluated clinical parameters as well as adult milestone achievement (i.e. education, employment, and marital status). Results: There were differences between the two groups (1999 vs. 2008, respectively) in employment status with a decrease in those working full-time (51% vs. 45%) and an increase in those characterized as disabled (14% vs. 22%). There were no differences in the milestones of education (completion of college; 40% vs. 41%) and married status (48% vs. 49%). Overall health had improved in all groups, with better lung function and nutritional status, including in those patients characterized as disabled (Table). Discussion: Clinical outcomes of adult CF patients have improved over the last decade. Despite the implementation of adult programs, there is no evidence of improved adult milestone achievement, and there has been an increase in the number of patients characterized as disabled. Patients characterized as disabled have also realized improvement in overall health, possibly because they are better able to attend to their health care needs. However, we should consider that the lack of an increase in milestone achievement may be because transition programs have not fully matured and require further development. Table: Comparison of 25-30 year-olds characterized in the CFFPR as disabled. 1999 2008 p value Disabled (%) FEV1 (median % predicted) BMI (%<20) College graduate (%) Married (%) Parent (%) Clinical Fellow 14.3 31.6 53.9 17.4 43.6 0 22.1 44.5 37.7 18.4 43.7 2.67 <0.0001 <0.0001 <0.0001 NS NS NS Poster #57 В The Colon Had an вЂњAirвЂќ About It: A Case of Symptomatic Pneumatosis Intestinalis Brunson MD, Brian, Andrew Hardie, MD, David Lewin, MD, Shaoli Sun, MD, Lawrence Comerford, MD Medical University of South Carolina, Charleston, SC Purpose: We present a case of pneumatosis intestinalis (PI) responsive to treatment with antibiotics and an elemental diet Case: An 87 year-old retired pathologist presented with a change in bowel habits, specifically alternating diarrhea and constipation, of 4 months duration. More recently, he experienced explosive non-bloody diarrhea with up to seven episodes daily, and a significant amount of bloating and flatus that at times was uncontrollable in social settings. He denied any upper GI symptoms or constitutional symptom s such as weight loss or fever. On physical exam, he appeared well and younger than his stated age. Lab work and stool studies were unremarkable other than a mildly elevated sedimentation rate. Celiac serology was negative. Due to his advanced age, he was treated conservatively and sequentially with a trial of a lactosefree diet, a 2 week course of rifaximin, probiotics, over-the-counter beano, cholestyramine and pancreatic enzymes with no improvement. After the failure of empiric therapies, EGD with duodenal biopsies was performed and was unremarkable. A colonoscopy, however, showed multiple areas of mucosal edema and polypoid appearing lesions in the transverse, descending colon, and sigmoid colon. Ischemia was considered due to reported intermittent hypotension, however, biopsies of the involved colon showed submucosal giant cell reaction suggestive of pneumatosis coli. CT enterography confirmed extensive left-sided colonic pneumatosis . He was then placed on a course of metronidazole. After two weeks with only minimal improvement, he was started on an elemental diet in combination with metronidazole, and his symptoms markedly improved. Repeat CT scan and colonoscopy (repeated for removal of a large adenomatous polyp) a few months later confirmed resolution of the pneumatosis. Discussion: вЂў PI is a rare condition marked by gas-filled cysts in the wall of the small or large bowel вЂў The true incidence is unknown since most patients are asymptomatic вЂў The course is variable and is largely determined by the underlying etiology вЂў It is often a benign and incidental finding, but can cause non-specific bowel symptoms вЂў In some cases (but not our case), PI may reflect a life-threatening abdominal catastrophe вЂў The pathogenesis is unclear and probably multifactorial, due to mechanical, biochemical, or bacterial causes вЂў The presence of portal venous gas or bowel obstruction is associated with the need for surgery вЂў Once an intra-abdominal catastrophe has been excluded, a variety of treatment options have been recommended based on a number of small case series вЂў Treatment options include long term antibiotics, elemental diet, high-flow oxygen, hyperbaric oxygen, or endoscopic cyst puncture or surgical therapy Conclusion: Pneumatosis intestinalis can cause gastrointestinal symptoms such as bloating and diarrhea and should be considered in patients who fail conservative treatment. Elemental diets and antibiotics may prove helpful in relieving symptoms presumably by altering the colonic gas producing microflora. Clinical Fellow В Poster #58 В Phase I Trial of the HDAC Inhibitor LBH589 in Combination with Sorafenib in Patients with Renal Cell Carcinoma, Non Small Cell Lung Cancer and Soft Tissue Sarcomas. Butler MD, Charles M1*, Lydia T Laboccetta MD2*, Alan Brisendine3*, Thomas E. Keane MD3*, and Harry A. Drabkin, MD3* 1 Division of Hematology/Oncology, Medical University of South Carolina, Charleston, SC; 2 Division of Urology, Medical University of South Carolina, Charleston, SC; 3Medical University of South Carolina, Charleston, SC. Introduction: LBH589 is a novel histone deacetylase inhibitor (HDACi) that induces apoptosis of tumor cells. In renal cell carcinoma (RCC) and NSCLC cell lines, the combination of sorafenib and HDACi was found to have synergistic inhibition, which correlated with the induction of an ER stress response. In this phase I study, we evaluated the combination of LBH589 and sorafenib in previously treated patients with RCC (9pts), soft tissue sarcomas (1pt), and non-squamous-non small-cell lung cancers (6pts). The trial was designed to determine the safety profile and maximum tolerated dose of LBH589 and sorafenib when administered concurrently. Methods: Patients were dosed with either i.v. (Days 1,8, and 15) or oral LBH 589 (three times per week, continuously) every twenty eight days in combination with standard daily dose sorafenib (400 mg bid). The dose escalation was based on a вЂњ3+3вЂќ algorithmic design. Results: Sixteen patients, median age 57 years, have been treated. Dose limiting toxicities were observed with grade 4 thrombocytopenia in two patients at the oral dose of 25 mg. There were no other grade 4 events. Grade 3 events included fatigue (2 pts), hypophosphatemia (2 pts), hypertension (1 pts), anemia (1 pt), rash (1 pt) and hand-foot erythroderma (1 pt). Common toxicities for the combination were fatigue (81%), weight loss (62%), loss of appetite (56%), diarrhea (56%), rash (50%), thrombocytopenia (31%), and hand-foot erythroderma (25%). There was 1 partial response in a patient with lung cancer (31 weeks). Stable disease was noted in seven patients with RCC (78+, 48, 47, 31, 21, 17, and 10+ weeks). Seven patients had progressive disease. Conclusions: The administration of oral LBH589 at a dose of 20 mg appears to be well tolerated. Prolonged stable disease was observed in patients previously treated with sorafenib alone, sunitinib and axitinib. Clinical Fellow В Poster #59 OUTCOMES OF PATIENTS WITH END STAGE LIVER DISEASE AND ACUTE KIDNEY INJURY REQUIRING DIALYSIS AT DISCHARGE Clark, Stephen D., David G. Koch, Roberto Pisoni, Ruth C. Campbell Department of Medicine, Divisions of Nephrology and Gastroenterology Medical University of South Carolina, Charleston, SC Acute Kidney Injury (AKI) is a common complication in patients with End Stage Liver Disease (ESLD). There is little data on the survival of ESLD patients with prolonged AKI who require dialysis after discharge. To determine the overall survival and potential for successful liver transplantation (LT) in this population, we retrospectively reviewed outcomes for adult (age > 18 yrs) ESLD patients with AKI who required dialysis at discharge at our institution over the past five years. Using ICD-9 codes and chart review, we identified patients with ESLD who developed AKI who were dialysis dependent at discharge. Patients who received a LT during the index hospitalization or who were on dialysis prior to the index admission were excluded. Twenty-one patients met the criteria for analysis. The median age was 54 (29-71) years. Sixty-two percent were male and 81% were Caucasian. The most common causes of ESLD were alcoholic cirrhosis (43%) and Hepatitis C (19%). The most common causes of AKI were hepatorenal syndrome (48%) and acute tubular necrosis (29%). Two patients were lost to follow-up and were not able to be included in the outcomes analysis. One patient regained renal function and stopped dialysis. Thirteen patients (68%) died with a median survival time of 45 (7-110) days. Seven patients were listed for LT either prior to or after discharge and 4/7 were transplanted (one liver and three liver-kidney) with a median time to transplant of 63 (30-210) days. Two patients died on the waiting list and one is still alive undergoing dialysis. In conclusion, dialysis for patients with ESLD and AKI after discharge may provide a bridge to LT. However, without LT, the outcome for these patients is very poor due to high mortality. Primary Author: Stephen Clark, MD Affiliation: Fellow, Division of Nephrology E-mail: clarksd@musc.edu Clinical Fellow Poster #60 В Does Timing/Delay of ERCP Affect Outcomes in Patients with Cholangitis? Craft M.D., Brandon, Fellow-Division of Gastroenterology/Hepatology AUTHORS: Brandon M. Craft1 , Peter Cotton1, Rob Hawes1, Christopher Lawrence1, Mark Payne1, Joseph Romagnuolo1 INSTITUTIONS (ALL): 1Department of Gastroenterology, Medical University of South Carolina, Charleston, SC, United States. Purpose: Cholangitis can be a life-threatening problem. However, many patients defervesce quickly on antibiotics, are easily resuscitated, and appear to tolerate waiting for ERCP days later, at the same or different/tertiary institution. Some institutions have a policy of urgent/same-day or within-24h ERCP, while others are more conservative, esp. on weekends when routine support may be absent, and in sicker patients allowing for complete resuscitation first. We tend towards the latter, but few published data support one approach over another. Methods: We retrospective reviewed patients admitted/transferred to our facility with cholangitis, documented from a billing database, or with cholangitis as the indication/outcome of an ERCP in the Endoworks database. We included patients with clinical cholangitis: fevers, elevated white blood cell count, and evidence of biliary obstruction (biochemical/imaging). Our focus was straightforward causes of cholangitis (common duct stone, occluded stent, or extrahepatic stricture) more consistently helped with ERCP; we excluded surgically altered anatomy, sclerosing cholangitis, and intrahepatic stones. Delay from time of presentation to ERCP was stratified into 4 groups: 0d delay, 1-2d, 2-5 days, or > 5 days. Results: 60 patients met inclusion criteria, with a mean age of 61, and 60% were male. 43% had stones, and 28% had occluded stents. All patients were managed with IV fluid resuscitation and antibiotics awaiting ERCP, with a spectrum of regimens. 31% were inpatient transfers, and 69% presented after hours. The average time from presentation of symptoms to ERCP was 2.57 d (range 0-17). 47 patients had fever, with 43 (81%) defervescing with antibiotics; 1 death occurred (1%), 6 (11%) patients were managed via an intensive care unit. 2 (3.8%) ERCPs were unsuccessful, and required PTC. 5 (9.4%) required repeat ERCP during their admission, and 4 (7%) adverse events occurred after ERCP, including 1 post-ERCP bleed, and 1 pneumonia. In all the cohort groups, if the patients had organ failure pre-procedurally it was noted on presentation, and no patient developed organ dysfunction while waiting on their procedure. Only 2 patients, one each from the earliest groups, developed organ failure post-procedurally. There did not appear to be a significant difference regarding clinical outcomes including death (only death was in early group from withdrawal of care for cancer patient), organ failure (12% for earliest, 20% for latest groups; p=0.7), or length of hospital stay (5-6 days) in patients undergoing ERCP for relief of obstruction at day 0, 1-2d, 2-5 days, or > 5 days Conclusion: In patients with ascending cholangitis, there does not appear to be a striking difference in outcomes between conservative management with antibiotics and intravenous fluids pending a delayed, semi-elective inpatient ERCP, versus earlier/urgent ERCP. Review of a larger cohort is ongoing Clinical Fellow В Poster #61 В Virologic Efficacy of Antiretroviral Regimens Containing Abacavir + Tenofovir Deol, Dilraj; Church, L.W. Preston; Salgado, Cassandra D. Division of Infectious Diseases, Department of Medicine. BACKGROUND: Abacavir (ABC)and tenofovir (TDF)are well tolerated and allow for once-daily dosing. Previous studies of ABC+TDF+3TC as a once daily triple nucleoside regimen were stopped prematurely because of high rates of virologic failure (VF). A number of reasons have been suggested to explain this, with the strongest evidence pointing to a low genetic barrier to resistance, leading to selection of drug resistance mutations. Consequently, some providers have been reluctant to combine these agents. Inclusion of an additional active antiretroviral agent from another class might be a successful strategy to achieve and maintain viral suppression (VS) in treatment experienced patients (pts) while offering convenient once daily dosing. METHODS: Records were reviewed on 468 HIV infected pts seen at the Ralph H. Johnson VAMC between 2000 and 2010. Pts on regimens of concurrent ABC and TDF were identified. HIV viral load, CD4 count, HIV genotype (if available) and medication refill history obtained throughout the course of therapy were recorded. VF was defined as failure to achieve HIV RNA<50 copies/ml or rebound in viral load defined by two consecutive measurements of >50 copies/ml. Nonadherence was defined as a medication possession ratio <.9. RESULTS: 37 pts were identified on regimens containing ABC+TDF and additional antiretrovirals not in the NRTI class. 20 (54%) maintained VS (HIV RNA <50) for a median of 28 months (range 2-62). 17 (46%) pts experienced VF. 11 of these 17 pts never achieved full VS and 6 experienced viral rebound after a median of 19.5 months. 13 patients failing therapy were identified as nonadherent . Therapy was switched among 8 pts and 4 developed complete VS while the other 4 continued to have detectable virus attributed to failure to adhere to the new regimen as well. 10 genotypes post VF detected new K65R and new K70R in 1 and 2 pts, respectively. CONCLUSIONS: Despite advances in antiretroviral therapy, options for once daily regimens are limited, particularly for pts that acquire the M184V mutation. Our observational study suggests that over 50% of pts assigned to a regimen of concurrent ABC and TDF achieved full VS when an active agent from another class was utilized and adherence was maintained. Medication nonadherence appeared to be the major reason for treatment failure Affiliation: Fellow Infectious Diseases-PGY 5. Type of Research Project: Clinical; Retrospective Observational Antiretroviral Therapy Study. Email ID: deol@musc.edu Clinical Fellow В Poster #62 Prevalence and Causes of Unexpandable Lung Over a Ten Year Period DiVietro, Matthew, Huggins JT, Doelken P, Gurung P, Kaiser L, Sahn SA, Medical University of South Carolina, Charleston Introduction: The development of an unexpandable lung is attributed to either visceral pleural restriction, chronic atelectasis, or endobronchial disease. Visceral pleural restriction due to active inflammation/infection or malignancy is defined as lung entrapment. Trapped lung is defined as visceral pleural restriction with the development of a fibrous pleural membrane in the absence of active inflammation/infection or malignancy. The diagnosis of an unexpandable lung is made by elevated pleural space elastance using manometry during thoracentesis. Methods: We identified 113 (39%) patients with unexpandable lung from a consecutive series of 291 patients with pleural effusion undergoing therapeutic thoracentesis with manometry from 2002 to 2011 at the Medical University of South Carolina. Clinical history, pleural manometry, and pleural fluid analysis were reviewed. Results: Trapped Lung n=60 Post Cardiac Surgery 15 (25.0%) Resolved Parapneumonic 12 (20.0%) Repeated Thoracentesis 11 (18.3%) Uremic Pleuritis 7 (11.6%) Unknown 7 (11.6%) Radiation Fibrosis 6 (10.0%) Amyloidosis 1 (1.6%) Hemothorax 1 (1.6%) Lung Entrapment n=50 Malignant 21 (42%) Parapneumonic 12 (24%) Paramalignant 9 (18%) Hemothorax 2 (4%) Tuberculosis 1 (2%) Idiopathic Fibrosing Pleuritis 1 (2%) Rheumatoid Pleurisy 1 (2%) Post Cardiac Surgery 1 (2%) Prolonged Chest Tube 1 (2%) Unknown 1 (2%) * 3 additional cases attributed to chronic atelectasis Clinical Implications The presence of an unexpandable lung defined by abnormal pleural space elastance is a common finding in patients presenting with pleural effusions. Most common cause trapped lung related to prior cardiac surgery, followed by remote parapneumonic, and then multiple thoracentesis. Greater than 60% of cases of lung entrapment are directly or indirectly related to underlying cancer. Clinical Fellow Poster #63 CYSTATIN C BASED EQUATIONS AS MARKERS OF RENAL FUNCTION IN AFRICAN AMERICAN LIVING KIDNEY DONOR Sunil Kumar Jain1, Amy H Wahlquist1, Paul J Nietert1, John M Arthur1, Milos N Budisavljevic1 ABSTRACT BODY: Purpose of Study: There are no data on serum creatinine (sCr) or Cystatin C (CysC) based equations that estimate glomerular filtration rate (GFR) in African American (AA) kidney donors. Since AA have an increased incidence of diabetes and hypertension, these donors may be at increased risk of kidney disease. Better methods are needed to follow renal function in these kidney donors over time. Our goals were to determine in AA kidney donors whether CysC is a better estimator of GFR than sCr and to determine which estimated GFR (eGFR) equation performs the best. Methods Used: Data were obtained from 33 AA who donated a kidney 5-21 years ago. GFR was measured (mGFR) by 125 I Iothalamate clearance. CysC was measured by particle enhanced turbidimetric assay. sCr was measured by enzymatic colorimetric assay calibrated to an isotope dilution mass spectrometry traceable method. Equations used for eGFR are listed in Table 1. Pearson correlation coefficients were calculated to determine which of the equation most highly correlates with mGFR. Summary of Results: The mean mGFR was 76.18 ml/min/1.73 m2. Pearson correlations between mGFR and eGFR from CysC and sCr based equations ranged from 0.51 - 0.81 (Table 1), all were statistically significant (p<0.01). Correlations were higher for the equations that used CysC compared to those that used sCr. Highest correlation was seen in CKD epi equation using both sCr and CysC. Conclusions: The use of the CKD epi estimating equation for GFR which uses both sCr and CysC provides an best correlation with mGFR and can be used to estimate the changes in renal function in AA kidney donors. Variables GFR ml/min (mean) SD Pearson Correlation p value mGFR 76.18 13.11 CysC Based eGFR, CKD unadjusted 77.36 17.54 0.7365 <0.0001 CysC Based eGFR, CKD adjusted 78.65 16.79 0.7851 <0.0001 Creatinine based eGFR, MDRD2 84.84 15.95 0.6683 <0.0001 Creatinine based eGFR, AASK 87.73 16.09 0.6754 <0.0001 Creatinine based eGFR, CG 107.87 35.21 0.5084 0.0025 Creatinine based eGFR, Nankivell 123.06 15.05 0.5756 0.0005 CysC & Creatinine based eGFR, CKD Epi 80.87 15.66 0.8067 <0.0001 Clinical Fellow Poster #64 В The Peroxidase Peroxiredoxin1 (Prdx1) promotes DNA double strand through Rad51 Jeter, M.D., Ashley A. Hematology/Oncology Fellow Medical University of South Carolina Many in vitro studies have supported the hypothesis that reactive oxygen species (ROS), such as H2O2, play a role in carcinogenesis by inducing DNA damage, lipid peroxidation, and protein structural and functional modifications. Ionizing radiation (IR) damages DNA mainly through ROS generated by the decomposition of water to its elements and H2O2. H2O2 is an important regulator of cell signaling through oxidation of low pKa catalytic cysteines in protein tyrosine phosphatases. Mice lacking Prdx1 die prematurely from cancer and hemolytic anemia and Prdx1-deficient cells have higher amounts of H2O2, IR-induced double strand breaks (DSBs) and reduced DNA repair activity. Here we demonstrate for the first time that Prdx1 promotes DNA repair dually by regulating Rad51 indirectly through Akt/Chk1 signaling and directly through protecting Rad51 from oxidation-induced inactivation. When compared to Prdx1 wild type cells, IR induces Akt activity and cytoplasmic retention of Chk1 to a higher extent in Prdx1 null cells, which in turn leads to a reduction of nuclear Brca2 and Rad51 loci formation and reduced DNA repair. Furthermore, Prdx1 binds directly to Rad51 protecting it from oxidation-induced inactivation and promoting its DNA repair activity. Using alkylation methods, we identified a Rad51 cysteine residues prone to oxidation and crucial for its activity. This cysteine when mutated to serine decreases Rad51 activity and sensitizes cells to PARP inhibition. Taken together, we provide the first mechanistic evidence that IR-induced ROS cause DNA damage by inhibiting its repair enzymes. At the same time we provide exciting novel evidence that Prdx1 plays an essential role in DNA repair. Clinical Fellow В Poster #65 URINARY BIOMARKERS IN PREDICTING PATEINT OUTCOME AND RENAL RECOVERY IN EARLY ACUTE KIDNEY INJURY Karakala, Nithin1, John M Arthur1, Nishant Bhensdadia1 1 Nephrology, Medical University of South Carolina, Charleston, SC, United States. ABSTRACT BODY: Purpose of Study: Acute Kidney Injury (AKI) is commonly seen in critically ill patients and is associated with increased mortality. Elevation of Cr, and decreased urine output cannot predict patient outcome and renal recovery in medical intensive care unit (MICU) patients early in AKI. We studied urine biomarkers concentrations for predicting renal recovery and outcome in ICU patients. Methods Used: Urine samples were collected from any patient who had AKI; Cr >0.3 mg/dl from baseline with in the first 24 hours of the initial diagnosis of AKI. Urine biomarker concentrations were measured using ELISA assays. Summary of Results: 31 patients were included in this study, 6 needed CRRT, 12 died in the hospital and 14 had renal recovery or survived without needing CRRT. The mean urine NGAL concentration in patients who had a combined outcome of CRRT and death in the hospital was 835В±146 ng/dl compared to 119В±49ng/dl in patient who had renal recovery or did not need renal replacement therapy (p<0.001). A NGAL value of в‰Ґ282.4 ng/ml had a sensitivity 72.2%, specificity 92%; AUC 0.801 for predicating CRRT or mortality in these patients. Other urine biomarkers (cystatin C, HGF and IL18) concentrations did not correlate with the clinical outcomes. Conclusions: Urine NGAL concentration appears to be very useful in predicting outcomes in ICU patients on the day of initial diagnosis of AKI. Clinical Fellow Poster #66 Progression of Pleural Fluid Acidosis and Inflammation in Acute vs. Chronic Hemothorax Kummerfeldt, Carlos1, DiVietro M1, Nestor J1, Huggins JT2 , Sahn SA2 1 Pulmonary Fellows and 2 Faculty, Department of Medicine, Division of Pulmonary and Critical Care Medicine, Medical University of South Carolina Introduction: Hemothorax is defined as pleural fluid/serum hematocrit (HCT) ratio > 50%. The pleural fluid findings in acute hemothorax are clearly defined in the literature, but findings in chronic hemothorax are not as well established. Methods: We identified 6 cases of hemothorax by clinical history, radiographic imaging and pleural fluid analysis from a database of 1133 cases undergoing thoracentesis from 2002 to 2010 at the Medical University of South Carolina. Results: Table. Six cases of hemothorax. The protein is given as g/dL with the pleural fluid to serum ratio in parenthesis; LDH is lactate dehydrogenase given as IU/L, RBC is red blood cell count given as cells/mm3, P HCT is the pleural fluid hematocrit in percentage, S HCT is the serum hematocrit in percentage, and ANC is absolute neutrophil count given as cells/mm3. Microbiology and pathology was negative in all cases. Clinical Implications: The development of inflammation correlates to the duration of blood in the pleural space. In chronic hemothorax (greater than one week), the pleural fluid analysis resembles a sterile empyema showing a low pH, elevated lactate dehydrogenase, and significantly elevated absolute neutrophil counts. We hypothesize that the following mechanisms may explain these pleural fluid findings in a chronic hemothorax. First, impaired clearance of carbon dioxide and lactate due to development of a fibrinous membrane and secondly a diminished erythrocyte Duffy antigen in old, lysed red blood cells both lead to impaired chemokine scavenging allowing for uncontrolled neutrophil recruitment. Research: clinical Clinical Fellow Poster #67 В De Novo Establishment of a Transradial Percutaneous Coronary Intervention Training Program for Cardiology Fellows: Safety and Efficacy Leonardi, MD, Robert A.*, Jacob C. Townsend, MD, David D. Bonnema, MD, Thomas M. Todoran, MD, MSc, Christopher D. Nielsen, MD, Eric R. Powers, MD, and Daniel H. Steinberg, MD Medical University of South Carolina Department of Medicine, Division of Cardiology *Fellow in Cardiovascular Medicine (email: leonarda@musc.edu) Background Radial arterial access for percutaneous coronary intervention (PCI) offers advantages over femoral arterial access, but cardiology fellowship training programs in the United States continue to produce cardiologists with little or no transradial (TR) training. The safety and effectiveness with which TR training programs can be established in academic centers is not established. Methods In July of 2009, a programmatic preference for TR catheterization was established in a training program for both general and interventional cardiology fellows. PCI-related data for the 20082009 (Y1) and 2009-2010 (Y2) academic years were prospectively collected and retrospectively analyzed. Baseline patient characteristics, procedural characteristics, and outcomes were compared across years (Y2 vs. Y1) and arterial access sites (radial vs. femoral). Results Of 1366 PCIs performed over both years, 193 of 673 (28.7%) in Y2 vs. 1 of 693 (0.1%) in Y1 were performed transradially. The TR PCIs in Y2 were performed by 13 different cardiology fellows and 9 different attending cardiologists, none of whom were routinely performing transradial PCI previously. Patients treated in Y2 vs. Y1 were more likely to have a history of diabetes (43 vs. 37%, p=0.04) or hypertension (92 vs. 84%, p<0.001). Patients undergoing TR vs. transfemoral (TF) PCI were heavier (91.1 vs. 86.7 kg, p=0.01) and had lower serum creatinine levels (1.1 vs. 1.4 mg/dL, p=0.01). Patients treated in Y2 vs. Y1 and patients treated with TR vs. TF PCI were less likely to be treated with glycoprotein 2b/3a inhibitors (2 vs. 15% in Y2 vs. Y1, p<0.001; 0.5 vs. 10% in TR vs. TF, p=0.002), required more fluoroscopy time (18.6 vs. 17.2 m in Y2 vs. Y1, p=0.05; 20.4 vs. 17.5 m in TR vs. TF, p=0.01) but similar contrast volumes, and were similar in terms of procedural duration, length of stay, and rates of procedural failure and pre-discharge mortality. Combined bleeding and vascular complication rates were lower in Y2 vs. Y1 (0.7 vs. 2.0%, p=0.05). Conclusions A TR PCI training program was safely and effectively established de novo at an academic medical center, significantly reducing the combined incidence of PCI-related bleeding and vascular complications in its first year. Given the advantages of radial arterial access for coronary arteriography and PCI, formal TR training should be an integral part of every cardiology fellowship training program. Clinical Fellow В Poster #68 В Biopsies of the nodules GAVE us the diagnosis Marsteller, William 1, MD, David Lewin2, MD, Adrian Reuben1, MBBS 1 Department of Medicine, Division of Gastroenterology and Hepatology 2 Department of Pathology Purpose: To describe an underappreciated endoscopic appearance of a common disorder, gastric antral vascular ectasia (GAVE). Case Presentations: We describe the cases of 3 patients who have a nodular form of GAVE. Our first patient is a 51 year old man with a history of cirrhosis due to non-alcoholic steatohepatitis who underwent evaluation with esophagogastroduodenoscopy (EGD) for iron deficiency anemia and was found to have multiple medium-sized antral nodules and mild linear antral erythema. The nodules were biopsied and the histopathology showed GAVE. Our second patient is a 61 year old woman with a history of cirrhosis due to non-alcoholic steatohepatitis who underwent evaluation with EGD for esophageal variceal surveillance and was found to have small esophageal varices, portal hypertensive gastropathy, and many antral nodules. The nodules were biopsied and the pathology showed GAVE. Of interest, she did not have any endoscopic evidence of GAVE other than the antral nodules. Our third patient is a 58 year old man with alcoholic cirrhosis who underwent EGD for iron-deficiency anemia and melena that showed antral nodules and punctate antral erythema in crops. Biopsies of the nodules showed GAVE. Discussion: GAVE is a well-established cause of iron deficiency anemia and rarely of overt upper GI bleeding. It is normally idiopathic, but can be associated with cirrhosis. It is defined histopathologically by vascular ectasias, spindle cell proliferation, thrombosis in venules and fibrohyalinosis. There are 2 classic endoscopic appearances of GAVE. The first is longitudinal red stripes in the antrum radiating proximally from the pylorus, which has been termed the вЂњwatermelon stomachвЂќ. The second is a punctate form that lacks the red stripes and is the more common form seen in association with cirrhosis. Nodular GAVE is a third phenotype of this disorder which is far less well-known and could easily be dismissed as a fundic gland or hyperplastic polyp, based only on the endoscopic appearance. Thus, taking biopsies of antral nodules is required to make the diagnosis. Conclusion: Nodular GAVE is a third endoscopic variant of GAVE, which can only reliably be differentiated from other gastric nodules/polyps through biopsy. Corresponding author: William Marsteller, GI fellow (marstel@musc.edu) Type of project: Clinical Clinical Fellow В Poster #69 The Prevalence of Lung Entrapment in Malignant Pleural Effusions: Does the pleural fluid analysis and chest radiograph predict the presence of abnormal pleural space elastance? Nestor MD, Jennings (fellow), John T. Huggins, MD (faculty), Steven Sahn, MD (faculty), Matthew DiVietro, MD (fellow), Carlos Kummerfeldt, MD (fellow) Pulmonary and Critical Care Medicine Abstract: Background: The frequency of abnormal pleural space elastance (PEL) in malignant pleural effusions (MPE) is unknown. Pleurodesis outcomes have been correlated to increase pleural space elastance (PEL) with the first 500 mL of fluid removed in one prior study. Methods and Measurements: We reviewed pleural manometry, pre- and post-procedural CXRs and identified 138 consecutive patients diagnosed with a MPE at the Medical University of South Carolina between January 2001 and January 2010. Of the 138 patients, 56 underwent therapeutic thoracentesis with pleural manometry, 59 underwent therapeutic thoracentesis without pleural manometry, and 23 underwent a diagnostic thoracentesis only. Pleural manometry was performed using both an over-damped, water manometer and an electronic acquisition system. Results: Abnormal PEL was identified in 33 of 56 (58.9%) patients. Twenty-five of 34 (73.5%) patients with PEL demonstrated a biphasic P/V curve, while 8 of 34 (26%) demonstrated a monophasic P/V curve with increase PEL. We found no statistical significant differences with regards to age, race, gender, tumor origin, tumor cell type, volume of pleural fluid drained, and pre- and post-procedural CXRs between the manometry and non-manometry groups. Similarly, no statistical significant difference was noted on the pre- and post-procedural CXRs between those with normal versus abnormal PEL. Volume loss or a post-procedural pneumothorax was uncommon in those with abnormal PEL. Conclusions: Abnormalities of lung expansion are more common than previously appreciated. This finding may have clinical implications by providing a physiologic explanation for the variability in pleurodesis success rates in MPE. Type of Research: Clinical E-mail Address of Corresponding Author: nestorj@musc.edu Clinical Fellow Poster #70 Combination of Bortezomib, Cyclophosphamide and Dexamethasone in Patients with Newly Dignosed Multiple Myeloma and Impaired Renal Function: Fast Improvement in Creatinine Clearance and Outcome Similar to Patients with Preserved Renal Function Ortiz-Cruz, MD, Karen,*1 Jonathan Abbas, MD1 Charles Butler, MD1Yubin Kang, MD1 Robert K. Stuart, MD1 Luciano J. Costa, MD PhD1 1 Division of Hematology and Oncology, Department of Medicine, MUSC * Fellow, Division of Hematology and Oncology, presenting author. Background: Near a third of patients with multiple myeloma present with renal impairment (RI). These patients have worse outcome than their counterparts with preserved renal function (PRF). We hypothesized that prompt treatment with a combination of bortezomib, cyclophosphamide and dexamethasone without dose adjustment for renal dysfunction will lead to fast disease response and reversal of renal dysfunction in RI patients and to outcomes similar to PRF patients. Methods: Retrospective analysis of consecutive patients with newly diagnosed symptomatic MM treated with induction therapy consisting of bortezomib 1.3 mg/m2 intravenously on days 1,4,8,11,22,25,29 and 32 , cyclophosphamide 300 mg/m2 intravenously on days 1,8, 22 and 29 and dexamethasone 40 mg PO on days 1,8,15,22,29 and 35 of each 6-week cycle (VCD). Treatment was started promptly once diagnosis was completed and not adjusted or modified for renal function or age. Patients were treated for up to 4 cycles followed, in eligible patients, by autologous hematopoietic stem cell transplantation with melphalan 200mg/m2. Patients reaching day 100 post transplantation or not eligible for transplantation received lenalidomide maintenance. Creatinine clearance (CrCl) was calculated at the diagnosis (once dehydration and hypercalcemia were corrected) and frequently throughout therapy utilizing the Cockcroft-Gault equation. None of the patients underwent plasma exchange for treatment of cast nephropathy. Results: Twenty-eight patients have received at least 2 cycles of VCD and are evaluable for response. Eleven patients had RI defined as CrCl<50 ml/min (median 22 ml/h, range 8-44 ml/min) and 17 patients had PRF defined as GFR в‰Ґ 50ml/min (median 104, range 50.2->120). Median age was 67 years in RI (range 48-71) and 60 years in PRF (range 30-80). Patients with RI were more likely to have light chain disease (45.4% vs. 5.8%) and international scoring system stage 3 (90.9% vs. 11.7%). High-risk chromosome abnormalities were detected by florescence in situ hybridization in 4/9 patients with RI and 6/15 patients with PRF. After a median follow up of 25 weeks, 100% of patients with RI and 88.2% of patients with PRF have reached at least a partial response (PR, P=0.24). Very good partial response (VGPR) has been reached in 72.7% and 35.3% (P=0.053) and complete responses (CR) in 36.3% and 16.6% (P=0.3) of patients in RI and PRF respectively. Responses were fast with median time to response (в‰ҐPR) of 6.4 weeks in RI and 8 weeks in PRF (Figure, panel a). All but one patient in RI had improvement in CrCl (Figure, panel b) with median CrCl for the group increasing from 22 to 55 ml/h. Grade 3 and 4 cytopenias were uncommon during induction but dose reductions of bortezomib were frequent due mostly to neuropathy. Four patients had at least one episode of hospitalization during the induction phase (2 with RI and 2 with PRF) and 2 patients (both with PRF) have discontinued therapy due to toxicity. There have been no progressions in either arm, although the follow up is short. Conclusion: Modern, triplet induction therapy with VCD is feasible in newly diagnosed MM patients with RI, leads to rapid reversal of renal dysfunction and response rates comparable to patients with PRF. Longer follow up is necessary to determine if the negative impact of RI in survival can be overcome with this approach. Clinical Fellow Poster #71 Distal Baseline Impedance (DBI) Is A Specific Diagnostic Marker For Achalasia Person MD, Erik, Erick Singh MD, & Donald Castell MD MUSC Internal Medicine / Gastroenterology Purpose: During esopheageal manometry, reduced distal baseline impedance (DBI) is believed to indicate fluid retention in the distal esophagus. Patients with achalasia are well known often to have a very low DBI due to inability to clear esophageal contents. The sensitivity and specificity of this marker has not been evaluated. This study tests the hypothesis that low DBI on impedance-manometry testing can accurately identify achalasia as a sole marker of disease. Methods: A retrospective analysis of 189 individuals who underwent esophageal function testing was performed and analyzed for DBI values using Sandhill BioView Analysis Software. These patients were divided into four groups; 50 healthy volunteers, 50 with a diagnosis of achalasia, 50 consecutive patients with various chief complaints, and 50 patients with a chief complaint of dysphagia. The software вЂњMedCalcвЂќ was utilized to calculate three receiver operating characteristic (ROC) curves to quantify the sensitivity and specificity of a range of DBI values in predicting the diagnosis of achalasia. In addition, the mean, median, mode, and confidence intervals of each data set were calculated. Results: The achalasia vs. healthy volunteers ROC curve demonstrated that DBI <=949 ohms carries 82% sensitivity and 90% specificity for the diagnosis of achalasia. The achalasia vs. consecutive patients group demonstrated that DBI <=718 ohms carries 72% sensitivity and 88% specificity for achalasia. DBI <=561 ohms carries a 60% sensitivity but 96% specificity for achalasia. The achalasia vs. dysphagia patients curve demonstrated that DBI <=561 ohms carries 59% sensitivity but 90% specificity for achalasia. DBI means were significantly lower in achalasia group as compared to other 3 groups. Conclusion: Reduced distal baseline impedance has low sensitivity but high specificity as a single measurement to predict achalasia. The high specificity of reduced DBI may be useful clinically to help characterize achalasia in patients with uncertain diagnoses. Type of Research Project: Clinical retrospective analysis Corresponding author: Erik Person, MUSC Internal Medicine Resident Clinical Fellow Poster #72 Lessons Learned from High Resolution Manometry - Inter-Observer Variability in Esophageal Body Measurements Amongst New Physician Users Rife, Christopher, Erick Singh, Steven Clayton, Peter Naas, Paul Nietert, & Donald Castell BACKGROUND: Esophageal high resolution manometry (HRM) has been heralded as an advance due to the ability to easily observe esophageal motility via the pressure topography plot. The topographic plot allows visual distinction between areas of rapidly conducted contractions and compartmentalized intraesophageal pressurization. Little is known about the inter-observer variability which physicians new to this technology may encounter. AIM: To evaluate inter-observer variability amongst new physician users with background training in esophageal motility on measures of esophageal body function via HRM. METHODS: Three resident or fellow level physicians each interpreted 10 liquid swallows of 20 esophageal HRM studies using the BioVIEW Analysis Suite (Sandhill Scientific, Inc.). Studies evaluated were from patients referred for evaluation of dysphagia but found to have normal esophageal manometry. Prior to study onset, the physicians received an orientation session structured by Sandhill Scientific, Inc, and also reviewed several recent publications regarding HRM. Each physician independently recorded pressurization front velocity (PFV) and distal contractile integral (DCI) for a total of 200 liquid swallows. STATISTICS: Inter-observer agreements for PFV and DCI were assessed by intraclass correlation (ICC) values. Linear correlations between measurements by two readers were assessed using linear regression modeling techniques. RESULTS - PFV and DCI values of up to 200 data points (10 liquid swallows of 20 patients) were analyzed for the three physicians. Three readers results for both PFV and DCI showed good to excellent correlation between readers, and was strongest for measures of DCI (ICC=0.99). PFV results showed good correlation (ICC=0.88), but with wider variability. Further correlation was performed with two readers who evaluated all 200 swallows to apply additional statistical measures. Comparison between readers 1 and 2 revealed excellent correlation with respect to DCI (r=0.95, p<0.001) and good correlation with PFV (r=0.61, p<0.001). CONCLUSIONS: HRM is an exciting new tool to assess esophageal body contractility. With an initial structured orientation session, good to excellent agreement for PFV and DCI measurements can be obtained from new physician users. PFV measures exhibit greater inter-observer variability possibly due to the phenomenon of intraesophageal pressurization. Multiple Observer Esophageal Body Contractile Measures and Correlation ( ) denotes 95% confidence interval Clinical Fellow Poster #73 Under-Reporting of Cardiopulmonary Incidents and Events During Endoscopy Utilizing Anesthesia Administered Mixed-Propofol Sedation Roberts MD, Jason, Peter Cotton MD, Robert Hawes MD, Christopher Lawrence MD, Mark Payne MD, Joseph Romagnuolo MD Division of Gastroenterology and Hepatology Background: Incidents and adverse events (AE) during endoscopy have been recently defined in an effort to standardize their reporting and allow for comparisons between studies. Endoscopic retrograde cholangiopancreatography (ERCP) is known to have the highest rate of overall incidents and AE among endoscopic procedures. Cardiopulmonary events are among the lowest reported AEs, but are among the highest cause of mortality; cardiopulmonary вЂњincidentsвЂќ (no clear clinically significant outcome or new intervention) are even less reliably reported. Endoscopists may be less aware of periprocedure changes to cardiopulmonary parameters when anesthesia administers/monitors sedation and not report them as incidents or AE, due to the anesthesiaвЂ™s comfort level with vasopressors, IV antihypertensives, etc. AIM: To determine the rate of significant hemodynamic changes requiring intervention by the anesthesiologist but are not reported as cardiopulmonary incidents or AE by the endoscopist. Methods: 125 consecutive patients underwent ERCP from November-December 2010. At our center, all ERCP sedation is administered by an anesthesiologist using mixed-propofol. Patients are generally nonintubated and are positioned prone. Endoscopy reports and anesthesia sedation notes were reviewed to collect patient demographics, American Society of Anesthesiologists score (ASA), dosage of propofol, fentanyl, and midazolam, as well as the use of vasopressors or intravenous antihypertensives. Planned intubation was distinguished from cases that converted to intubation. Results: 101 patient charts had complete data and were included in analysis. The mean patient age was 52 (14-91) and 64 were female; 5% were ASA-1, 49% ASA-2, 45% ASA-3, and 2% ASA-4. There were 14 cases with planned intubation (2 ASA-2, 10 ASA-3, 2 ASA-4) and 4 required conversion to intubation for hypoxia (3 ASA-2, 1 ASA-3). The mean anesthetic doses used for propofol, fentanyl, and midazolam were 79.0mg (0-400mg), 91.6mcg (0-300mcg), and 2.2mg (0-5mg) respectively. Vasopressors (phenylephrine) were used in 17 cases (6 ASA1-2 vs 11 ASA 3-4, p=0.08) with a mean dose of 432.9mcg (80-1280mcg). None of the hemodynamic changes requiring vasopressors resulted in AEs however 30 day data are still being collected. Pressor use was not recorded in any endoscopy reports. Conclusion: The low rate of cardiopulmonary incidents and AE reported in the literature may be the вЂ�tip of the iceburgвЂ™ in anesthesia-administered cases, due to under-reporting of vasopressor use for hemodynamic changes occurring during endoscopy. Although these would be classified as incidents, delayed AE occurring within 30 days are still being collected; pressor use without an anesthesiology team sedating would likely have been coded differently and affects comparative safety analyses. Clinical Fellow Poster #74 В Complications of Atrial Fibrillation Ablation in Patients Anticoagulated with Dabigatran Compared to Warfarin Rowley, Christopher P., Natalie S. Bradford, Michael L. Bernard, Peter C. Netzler, Darren S. Sidney, William W. Brabham, Frank Cuoco, J. Lacy Sturdivant, Robert B. Leman, Michael R. Gold, J. Marcus Wharton Division of Cardiology, Department of Medicine. Medical University of South Carolina Introduction: In order to decrease the risk of thromboembolic complications, patients (pts) with atrial fibrillation (AF) who are undergoing ablation are anticoagulated with either warfarin or more recently dabigatran. However, tests to monitor compliance with dabigatran are not readily available as they are with warfarin. The present study evaluates efficacy and safety of dabigatran compared to warfarin prior to AF ablation. Methods: We retrospectively evaluated 282 pts undergoing AF ablation who were anticoagulated with either dabigatran (113 pts) or warfarin with enoxaparin bridging (169 pts) before and after AF ablation. Efficacy endpoints were stroke, TIA, or peripheral embolus at the time of or within 30 days of ablation. Safety endpoints were major life threatening vascular complications (e.g. RP bleed) and non-life threatening vascular or bleeding complications (e.g. AV fistula, pseudoaneurysm, bleeding requiring transfusion of blood products, and hematoma requiring further diagnostic evaluation or intervention at the time of or within 30 days of ablation. Results: The mean age (63 В± 10 years old) and CHADS2 score (1.3 В± 1) were similar between groups. Dabigatran pts received their last dose the day before AF ablation and typically restarted the day following ablation. Warfarin pts received enoxaparin the day before AF ablation and typically resumed warfarin the day after with bridging enoxaparin until INR >1.8. The primary efficacy endpoint occurred in 2 (1.7%) dabigatran and 2 (1.2%) warfarin patients (RR 1.49, 95% CI 0.21 to 10.41, p=0.69). There was one stroke and one TIA in the dabigatran group and one stroke and one PE in the warfarin group. There was 1 major life threatening vascular complication (RP bleed) in the warfarin group and none in the dabigatran group. Non-life threatening vascular complications occurred in 5 (4.4%) dabigatran and 33 (19.5%) warfarin patients (RR 0.26, 95% CI 0.10 to 0.65, p=0.004). Conclusion: Pts undergoing AF ablation who are anticoagulated with dabigatran have significantly fewer complications compared to patients receiving warfarin with enoxaparin bridging without an increased risk of stroke. Thus dabigatran is the preferred anticoagulation strategy prior to AF ablation. Corresponding author: Christopher Rowley, MD., Fellow in cardiovascular disease Email: cpr3@musc.edu Abstract Category: Clinical science Clinical Fellow В Poster #75 В Impact of Contrast-Induced Acute Kidney Injury on Progression to End-Stage Renal Disease Among Subjects with Preexisting Advanced Chronic Kidney Disease Salazar, M.D., Maria Nieva 1, Christopher D. Nielsen, M.D.2, Juan Carlos Q. Velez, M.D.3 Fellow, Division of Nephrology; 2Faculty, Division of Cardiology; 3Faculty, Division of Nephrology 1 Growing evidence indicates that acute kidney injury (AKI) may cause new-onset end-stage renal disease (ESRD). However, the impact of contrast-induced AKI (CI-AKI) on long-term renal survival remains unknown. We hypothesized that CI-AKI is an underreported cause of progression of chronic kidney disease (CKD) to ESRD or death, and that standard preventive measures are not consistently implemented. Thus, we conducted a retrospective review of patients who underwent contrast-enhanced cardiac catheterization over the last 2 years. Since the risk of CI-AKI is proportional to the severity of preexisting CKD, we included subjects with estimated glomerular filtration rate (eGFR) < 45ml/min pre-procedure. CI-AKI was defined as в‰Ґ 25% increase in sCr within 48-96 hours post-procedure. CKD Progression was defined as decrease in eGFR в‰Ґ10ml/min within 3-12 months post-procedure. Of 98 subjects identified, 53 were excluded because of unavailable sCr after 48 hours post-procedure. The incidence of CIAKI was 24% (11/45). Among them, 2/11(18%) reached ESRD, 3/11 (27%) had CKD Progression and 1/11 (9%) died. The composite endpoint of CKD Progression, ESRD or death, after CI-AKI, was reached by 13.3% (6/45) of the subjects, occurring more often in those who developed CI-AKI compared to those who did not developed CI-AKI [55% (6/11) vs. 9% (2/22); p=0.0037] Among those with CKD stage 3B (eGFR 30-45ml/min), 6/22 (27%) developed CIAKI: none developed ESRD, 3/6 (50%) had CKD Progression and 1/6 (16%) died; whereas among those with CKD stage 4 or lower (eGFR в‰¤ 30ml/min), 5/23 (21%) developed CI-AKI: 2/5 (40%) progressed to ESRD but none died. Isotonic volume expansion with saline and/or bicarbonate was given to 64% (7/11) of the patients who developed CI-AKI. Moreover, such intervention was only implemented in 40% (2/6) of those who reached the composite endpoint, whereas 83% (5/6) of them received N-acetyl-cysteine, a drug with marginal benefit. Cognizant of the limitations of our study, we conclude that CI-AKI may have an ominous long-term impact in subjects with advanced CKD. There appears to be room for improvement on the systematic implementation of preventive measures and post-procedural testing. E-mail: salazarm@musc.edu Clinical Fellow Category Clinical Fellow В Poster #76 В Are Protocol Biopsies Useful for Predicting Renal Transplant Recipient Outcomes? Shahira MD, Eram, Elizabeth Chua, MD M Aurora Posadas, MD, Beje Thomas, MD, M Francesca Egidi, MD. Transplant Nephrology, Medical University of South Carolina, Charleston, South Carolina, United States. Background: Data is conflicting regarding the utility of protocol biopsies (PB) to identify subclinical rejections and prevent graft dysfunction. Our center began doing PB at 4-8 wks after kidney transplant (KTX). The aim of this study was to analyze the predictive and clinical value of PB. Methods: Cross-sectional analysis of KTX recipients who underwent PB from 2009-10. PB was read by pathologists based on Banff criteria. Patients received ATG or anti-IL-2 receptor induction followed by FK, MMF, and steroids. Treatment of PB was left to the discretion of the physician. Groups were divided based on PB: normal, abnormal (ATN or arteriolar Hyalinosis AH), or borderline rejection. One PB showed mild acute rejection and was included in the borderline group. Results: 120 patients had PBs that were analyzed. Baseline demographics between the 3 groups were similar [table 1]. Of the 44 patients with abnormal biopsy, 22 had borderline rejection,17 of whom did not receive anti-rejection treatment. None of these patients went on to develop acute rejection. 18% of the PBs demonstrated abnormal results with ATN/AH. The serum creatinine (SCr) in this group were significantly higher early post-KTX (1 and 6 months), but equilibrated long-term (12-24 months). Table 1- Baseline Characteristics Table 2 - FK and SCr Level Conclusions: PB showed a relatively high rate of borderline rejection, supporting the usefulness of PB in identifying and treating borderline rejection. However, we also showed that patients with borderline rejection did not go on to have subsequent rejection and continued to have stable renal function. Some also showed ATN/AH, which correlated with significantly higher SCr. Our data reveal that PBs may be useful in recognizing patients that would benefit from modification of CNIs to prevent or minimize chronic toxicities. Clinical Fellow В Poster #77 Natural History of Hepatocellular Cancer in Setting of Liver Transplantation at a Single Transplant Institution and Evaluation of Pre-operative Investigation and Post-Operative Surveillance for Recurrent Hepatocellular Cancer Simpson, Heather, Adrian Reuben, David Lewin Department of Internal Medicine - Division of Gastroenterology Background: Hepatocellular cancer is the third leading cause of cancer related deaths in the world. Liver transplantation has become a leading treatment for hepatocellular cancer, although not every patient is a candidate for liver transplant. We reviewed a large number of patients referred to the Medical University of South Carolina for liver transplantation that were found to have hepatocellular cancer. This study evaluates the natural history of hepatocelluar cancer by monitoring patient outcomes including the following: survival, recurrent hepatocellular cancer, yield of hepatocellular cancer surveillance studies post-transplant, and utility of diagnostic lab tests and imaging for hepatocellular cancer in pre-transplanted patients. Methods: We conducted a restrospective analysis of 162 patients referred to the Medical University of South Carolina for liver transplantation prior to May 30, 2009. Patients included in the study had to be at least one year out from their initial transplantation evaluation. Data reviewed included laboratory tests, radiologic imaging, pathology specimens, history from clinic notes, demographics of the patient population, and etiology of liver disease. All patients were de-identified and information was placed into a de-identifed database. Results: 93 patients were known to have hepatocellular cancer at the initial transplant evaluation based on confirmatory imaging or biopsies of the tumor, while 45 patients were found to have hepatocellular cancer during the transplant evaluation process. In addition, 24 patients were found to have hepatocellular cancer in their explanted liver specimens that were previously not thought to have hepatocellular cancer during their transplant evaluation. Conclusion: Liver transplantation is an effective and novel treatment for patients with hepatocellular cancer in patients with a limited number of tumors that are of a small size. However, the preoperative evaluation does not always accurately identify the prevalence of hepatocellular cancer in patients with cirrhosis. Extensive follow up labwork and imaging in transplanted patients rarely reveals recurrent hepatocellular cancer. Email: simpsoh@musc.edu Clinical Fellow Poster #78 Relevance of Renal glucosuria in proteinuric glomerular diseases Talwar, Manish1; Nietert, Paul2, Self Sally3, Velez, Juan Carlos Q1 Institution: 1Division of Nephrology, Dept. of Medicine 2Division of Epidemiology and Biostatistics, Dept. of Medicine. 3Department of Pathology Dipstick glucosuria is occasionally observed in non-diabetic proteinuric glomerular diseases, even in the absence of hyperglycemia. However, its frequency and potential association with disease severity is unknown. We searched for pathology reports of adult patients who underwent percutaneous kidney biopsy at MUSC between 1998 and 2011, indicated for proteinuria. Accordingly, we included reports with a diagnosis of focal segmental glomerulosclerosis, membranous glomerulopathy, minimal change disease, membranous lupus nephritis, amyloidosis, light chain deposition disease and HIVassociated nephropathy, all proteinuric glomerulopathies. Since proliferative glomerular diseases are typically nephritic in nature, they were not included in our study. Subjects with diabetes or those taking tubulo-toxic medications were also excluded. Demographics and laboratory values were collected, including serum creatinine, estimated glomerular filtration rate (eGFR) and urine protein-to-creatinine ratio (UPCR). Glomerular and tubulointerstitial chronicity indices were extracted from pathology reports. We identified 147 patients who met our selection criteria. Among them, 13 patients were found to have renal glucosuria. Our analysis revealed that patients who presented with dipstick glucosuria were characterized by a higher serum creatinine, lower eGFR and higher UPCR at the time of the kidney biopsy, compared to those without glucosuria [3.93 +/3.48 vs. 1.83 +/- 1.72, p=0.0001; 28.69 +/- 18.08 vs. 65.51 +/- 38.41, p=0.0002; 9.17 +/5.09 vs 5.46 +/- 5.52 p= 0.010 respectively]. Histopathological scores were not significantly different between groups. In addition, presence of glucosuria did not help discriminate among diseases. Our study is limited by its retrospective nature. Quantitative urine glucose is not routinely obtained; therefore, it was not available to us. We conclude that renal glucosuria is a feature of more advanced forms of proteinuric glomerular diseases as evidenced by its correlation with worse kidney function and heavier proteinuria. We speculate that it may represent a marker of tubular damage or impairment of glucose tubular handling. Type of Project: Clinical Fellow Corresponding author: Talwar, Manish (talwar@musc.edu) Clinical Fellow Poster #79 В Inhaled Tobramycin Timing Alters Intravenous Tobramycin Concentrations Stenbit MD, PhD, Antine E. Wendy M. Bullington, PharmD, Julie L. Heh, Pharm D, and Patrick A. Flume, MD Department of Medicine, Division of Pulmonary and Critical Care Department of Clinical Pharmacy Services Aerosolized tobramycin inhalation solution (TIS) may be absorbed and result in measurable serum levels. This could affect calculation of pharmacokinetic (PK) parameters and dosing if TIS is used concurrently with intravenous (IV) tobramycin for treatment of a pulmonary exacerbation. Computer PK modeling predicts that TIS given in the latter portion of the IV dosing interval would result in increased tobramycin trough levels in some patients. We wanted to assess the significance of timing of TIS on IV tobramycin trough levels in the clinical setting. Adult CF patients infected with P aeruginosa admitted to the hospital for treatment of a pulmonary exacerbation were eligible for the study. IV tobramycin was dosed every 12 hours based on previous PK measures for a planned tobramycin trough <1mcg/ml. Tobramycin levels were drawn approximately 2 and 9 hours after an IV dose. The following day, tobramycin levels were again drawn at 2 and 9 hours, but TIS was given 5-9 hours after the IV dose. Sixteen patients have participated thus far. All tolerated the IV tobramycin and TIS without any adverse effects. Seven patients had a clinically significant change in the tobramycin trough level and 3 of those patients had an increase in their trough level >2mcg/ml. Seven patients had a doubling of their trough. Eight patients had a reduced elimination rate constant after TIS administration, which may be misinterpreted by the medical team as a perceived decreased in clearance of IV tobramycin. The creatinine remained stable throughout the treatment in all patients. Conclusion: Trough tobramycin levels were significantly influenced in some (44%) of CF patients following aerosolized TIS when given in the latter part of the IV dosing interval, consistent with significant absorption of inhaled drug in some patients. This study does not address the efficacy or safety of TIS when given concomitantly with IV tobramycin. However, these findings suggest that timing of the inhaled dose should be considered when interpreting PK measures of IV drug dosing. This project was supported by a generous grant from the Novartis Pharmaceuticals Corporation. В Clinical Junior Faculty В Poster #80 В The Impact Of a Health Information Exchange on the Management of Patients in an Urban Academic Emergency Department: An Observational Study and Cost-Benefit Analysis Carr, Christine, Krywko, DM, Saef, SH, Medical University of South Carolina, Charleston, SC Abstract: Background: Health Information Exchanges are systems designed to electronically move clinical information among disparate health care information systems while preserving the integrity of the information being exchanged. An HIE was recently made available to clinicians in the Emergency Departments (EDs) of the four major hospitals in greater Charleston, SC. We conducted a pilot study to evaluate the impact of this HIE on the management of ED patients at the academic medical center and trauma center for the region. Objectives: Characterize how access to an HIE modified the care of patients presenting to an urban academic medical center and trauma center. Perform a cost-benefit analysis based on the data obtained. Methods: The study site was the ED at an urban level I trauma and tertiary care center at a southeastern academic medical center. The study design was prospective, observational using a voluntary, anonymous survey administered to ED clinicians asking how access to an HIE influenced their decisions regarding patient management. Survey items addressed whether information from the HIE avoided the use of resources. Items used branching logic to ascertain the specific types of services being avoided including laboratory and radiologic testing, consultations, prescription of medications, performance of procedures, and arrangements for hospital admission. Additional items asked how the HIE affected the overall quality of care and length-of-stay. The survey was automated using a survey construction tool (REDCap Survey Software В© 2010 Vanderbilt University) which also collated and summarized the results. A cost analysis was performed using actual dollar values multiplied by the numbers and types of services avoided. Results: One hundred thirty-eight surveys were completed of which 105 were for patients who had information available in the HIE. Within this group the following services were avoided [number of studies (% of those who had information in the HIE)]: Laboratory/Microbiology: 32 (30.5%); Radiology studies: 50 (47.6%); Consultations 20 (19%); Prescriptions: 13 (12.4%); Procedures: 1 (0.95%), Admission: 12 (11.4%). Changes in management other than avoidance of a service were made for 34 (35%). Ninety-one (86.7%) of participants stated that the quality of care delivered to their patients had been improved. Eighty five (81%) reported that valuable time was saved with a mean time saved of 2 hours. Cost savings during the 4 month study period were as follows: Laboratory: $462.85; Radiology: $163,893.00; Consultations: $5,250.00; Admissions: $120,000.00; Grand Total: $286,605.85. Conclusions: Observational data provided by ED clinicians in a urban academic medical center showed a noteworthy reduction in resource use as a result of having access to an HIE involving the 4 major hospitals in the area. Total cost savings during the 4 month study period based on resource avoidance was $286,605.85 with the principal contributions coming from avoided radiologic studies ($160,893.00) and admissions ($120,000.00). The pilot data obtained from this study justifies further investigation regarding the ability of an HIE to affect management of patients who come to Emergency Departments in our region. Limitations include the observational nature of the study, selection bias, and the Hawthorne effect. Clinical Junior Faculty В Poster #81 Tandem autologous transplantation vs. autologous plus reduced intensity conditioning (RIC) allogeneic transplantation in the management of newly diagnosed multiple myeloma: meta-analysis of prospective trials with biological randomization. Costa, MD, PhD, Luciano J. 1*, Kent E Armeson, MS 2, Elizabeth G. Hill, PhD 2 1 Division of Hematology and Oncology, Department of Medicine, MUSC Division of Biostatistics and Epidemiology, Department of Medicine, MUSC *Presenting author 2 Introduction: Autologous transplantation has a defined role in the upfront treatment of multiple myeloma (MM) but nearly all patients will eventually relapse. Allogeneic transplantation carries the benefit of graft versus myeloma (GVM) effect but also high risk of treatment related mortality (TRM). Trials randomizing patients with newly diagnosed MM to tandem autologous (TA) or the combination of autologous + RIC allogeneic transplantation (AR) based on the availability of an HLA-matched donor have yielded heterogeneous results. We performed a meta-analysis of all reported trials comparing TA with AR transplantation in newly diagnosed MM to summarize the available evidence supporting the upfront use AR in multiple myeloma. Methods: We utilized a comprehensive search strategy to identify all trials meeting the following entry criteria: prospective trial, inclusion only of newly diagnosed patients (typically after conventional induction therapy), subjects undergoing similar induction therapy and first autologous transplantation in both arms, assignment to RIC allogeneic transplantation or a second autologous transplantation based exclusively on the availability or not of a HLA matched donor, use of RIC and report of at least overall survival (OS) and/or progression-free survival (PFS) as endpoint. OS analyzed per intention to treat (ITT) was the primary endpoint. PFS, complete response (CR) rate and rate of TRM were secondary endpoints. Results: We identified 6 trials meeting entry criteria. There were 1192 patients assigned to TA and 630 patients to AR. Relative to TA, AR patients were more likely to experience TRM (OR = 3.1, 95% CI = 2.1 to 4.5), but not more likely to achieve CR (OR = 1.2, 95% CI = 0.9 to 1.7). There was no statistically significant difference in PFS within the first 36 months (HR = 1.1, 95% CI = 0.9 to 1.3) or beyond 36 months from transplant (HR = 0.9, 95% CI = 0.7 to 1.3). Similarly, there was no significant difference in OS between the arms within 36 months (HR = 1.2, 95% CI = 0.9 - 1.5) or beyond 36 months (HR = 1.1, 95% CI = 0.7 - 1.6). Conclusion: We conclude that AR is associated with substantially higher TRM but with no improvement in PFS or OS over TA transplantation in the initial management of patients with MM. Allogeneic transplantation in this setting remains experimental. Innovative approaches are needed to improve the safety and efficacy of this strategy. Category: Junior Faculty, Clinical Science Email: costalj@musc.edu Clinical Junior Faculty Poster #82 В Demographic description of patients testing positive during non-targeted HIV testing in an academic tertiary care emergency department. Glover, Neil, Shapshak D, Green M, Navarro R, Houck R, Fesperman C. Division of Emergency Medicine, Department of Medicine Objective: Describe the HIV population diagnosed by non-targeted HIV testing in the emergency department. Methods: The MUSC Emergency Department is an academic, tertiary care facility with a 40 bed capacity. From May 2008 to November 2011, MUSC offered routine, non-targeted testing at no cost for Emergency Department patients aged 18 to 64. Trained research assistants offered UniGoldв„ў RecombigenВ® HIV, rapid immunoassays to patients during their ER treatment course. Patients diagnosed with HIV were linked to follow-up care with infectious disease specialists. Results: Of 10,985 patients approached, 7543 accepted testing and 3,442 declined. 44 patients were newly diagnosed with HIV infection. The age distribution of newly positive patients ranged from 18 to 64. 10 were female; 34 were male. Race distribution was 2 White, 2 Latino and 40 African-American. 35 patients presented with symptoms related to infectious diseases. 22 patients had initial CD4 counts less than 200. 15 patients had AIDS defining illnesses. 73% percent were uninsured compared to 47% of the general emergency department population. Conclusions: The 2006 CDC guidelines recommend routine HIV screening in emergency departments where the incidence of undiagnosed HIV infection is greater than 1 in 1000. An incidence of 6/1000 supports continued HIV screening of our ED population. Being male, uninsured, African American presenting with infectious and constitutional complaints appears to be associated with positive HIV testing in our population. Type of Research: Clinical Research Corresponding Author: Dag Shapshak MD Email: shapshak@musc.edu Clinical Junior Faculty В Poster #83 Impact of Long-Term Medication Non-Adherence on Mortality Differs by Race/Ethnicity among Veterans with Diabetes Lynch MD, MPH, Cheryl P1, Mulugeta Gebregziabher, PhD2, Kelly J Hunt, PhD2, Patrick D Mauldin, PhD1, Leonard E Egede, MD, MS1 1 Division of General Internal Medicine & Geriatrics, 2Division of Biostatistics & Epidemiology, Department of Medicine, MUSC OBJECTIVE: Medication non-adherence (MNA) is linked to adverse outcomes including poor glycemic control, increased hospitalization, and higher all-cause mortality. The longitudinal effect of MNA on all-cause mortality by race/ethnicity was examined in a national sample of veterans with type 2 diabetes. METHODS: A longitudinal cohort of veterans with diabetes was created by linking patient and administrative files from 2 large Veterans Administration databases. The outcome was time to death (in months) between date of study entry and date of death (or censored or May 2006). Predictors were race/ethnicity and mean medication possession ratio (MPR) categorized into quintiles for each veteran. Cox regression models assessed time to death and MPR by race controlling for sociodemographics, medication class (oral, insulin, both), and medical and psychiatric comorbidities. Hazard ratios (HR) for mortality risk were computed for race and MPR quintiles and the race-MPR interaction was tested. RESULTS: The cohort comprised a total of 629,563 male (97.8%) veterans with type 2 diabetes followed over 5 years. After covariate adjustments, HR for veterans in the lowest MPR versus highest quintile was 12.21 (95%CI 11.89,12.55) for non-Hispanic white (NHW), 10.01 (9.18,10.91) for non-Hispanic black (NHB), 12.65 (11.10,14.43) for Hispanic and 10.41 (9.06,11.96) for Other race veterans. Compared to oral medication only, combined therapy was linked to lower mortality risk among NHW 0.90 (0.89,0.92), NHB 0.91 (0.87,0.95), and Hispanics 0.88 (0.82,0.95), but insulin use showed lower mortality risk among NHW 0.94 (0.93,0.96) and higher in Hispanic veterans 1.09 (1.03,1.16). CONCLUSIONS: This study demonstrates clear evidence of a substantially higher mortality risk in the lowest MPR quintile relative to the highest quintile for all racial/ethnic groups; the association being strongest in NHW veterans. These findings suggest a need for novel interventions to improve medication adherence in diabetes, more aggressive titration of medications, and early use of combined therapy across racial groups. Type of Research Project: Clinical Science Email: lynchcp@musc.edu Clinical Junior Faculty Poster #84 В Differences In Perception About Access To Care Between Patients Who Choose An Urban Academic Emergency Department Over A Community-based Student-run Free Clinic For Non-urgent Care Saef, Steven H.1, C. Cohen2, M. Dettmer3, E. C. Jauch1, B. Walker1, W. Gonsalves1, K. N. Simpson1; 1 Medical University of South Carolina, Charleston, SC, 2UC Davis Health System, Sacramento, CA, 3Washington University Medical Center/Barnes-Jewish Hospital, St. Louis, MO. Abstract: Background: Uninsured patients often choose the Emergency Department (ED) over other suitable venues for non-urgent care. Understanding patient preferences and obstacles to nonurgent care can improve access to care. Objectives: Characterize differences in perception about access to non-urgent care by uninsured patients who present to an urban academic ED vs. a community-based student-run free clinic (FC). Methods: We compared responses of uninsured patients with non-urgent complaints presenting to an urban academic level I trauma/tertiary care ED with those of a FC using a prospective, anonymous survey. Survey items evaluated patients' perceptions about access to care which might explain their choice of venue. ED patients with Emergency Severity Index (ESI) categories 4 or 5 and selected category 3 patients (ambulatory, normal mental status, skin warm and dry, no signs or symptoms of vital organ compromise) were deemed non-urgent. All patients presenting to the FC were deemed non-urgent. The study instrument was a 10 item survey addressing Desirability of a FC over the ED (DFE); Transportation Status (Access to a Car); Perceived Quality of Care; Usual Place of Care; Importance of Cost; Self-Perceived Level of Illness (SPLOI); distance to ED or FC, and patient demographics. All items were answered on a 5-point Likert Scale. Scores from like items addressing similar concerns were combined. A convenience sample of 100 patients was obtained from each site. Comparisons were made using StudentвЂ™s t-Test. Logistic regression was used to adjust for the effect of significant variables, demographics, and distance on the response to the item about DFE. Results: Differences were noted between the ED and FC patients for items regarding Cost (ED mean 4.31, FC mean 3.68; p=0.03) with ED patients showing less concern about cost; Transportation (ED mean 7.00, FC mean 8.01; p=0.003) with ED patients showing greater concern about access to a car; and SPLOI (ED mean 2.87, FC mean 3.40; p=0.01) with ED patients perceiving themselves as more ill. No difference was noted between the groups regarding DFE after adjustment (p=0.68). Conclusion: Non-urgent, uninsured patients presenting to the ED showed less concern about the cost of care, greater concern about transportation, and felt themselves to be more ill than those presenting to a FC. No difference was noted between the groups regarding DFE after adjustment. Clinical Junior Faculty В Poster #85 В Copper Surfaces (CuS) Significantly Lower Rate of Hospital Acquired Infections (HAIs) in the Medical Intensive Care Unit (MICU) Salgado, Cassandra1, KA Sepkowitz2, JF John3, JR Cantey1, U Rappo2, H Baig3, S Singh2, HH Attaway4, HT Michels5, MG Schmidt4 1 Division of Infectious Diseases, Department of Medicine MUSC, 2Division of Infectious Diseases, Department of Medicine MSKCC, 3Department of Medicine RHJVA, 4Department of Microbiology and Immunology, 5MUSC, Copper Development Association Background: The role of environmental surface contamination to HAIs has not been well defined. Previously we reported that CuS reduced environmental bioburden by >90% in MICU patient rooms. We now report the effect of CuS on HAIs among MICU patients. Methods: Patients admitted to the MICU in 3 hospitals from 7/12/10 - 5/13/11 were randomly placed into rooms with either standard (plastic, wood, stainless or chrome) surfaces or rooms with CuS (bedrails, IV pole, overbed table, chair, monitor bezel and call button). Patients were followed prospectively for HAI or for new MRSA or VRE colonization. Results: 564 patients were admitted over the study period; 269 (47.7%) to rooms with CuS. There was no significant difference in age, sex, race, APACHE II score or MICU LOS between study groups. The overall HAI rate was 12.23 per 1000 patient days and was significantly lower in copper vs. standard rooms [8.95 vs. 15.16, OR 0.55 (95%CI 0.41-0.73), p=0.00003]. Additionally, the overall MRSA or VRE acquisition rate was 7.55 per 1000 patient days and was significantly lower in copper vs. standard rooms [6.12 vs. 8.8, OR 0.67 (95%CI 0.47-0.96), p=0.03]. In the subpopulation of patients admitted to rooms where all 6 objects with CuS remained in the room for the entire MICU stay, there was an even greater effect on reduction of HAIs vs. those never exposed to CuS [6.88 vs. 15.72, OR 0.40 (95%CI 0.29-0.54), p<0.0001]. Conclusion: CuS reduce environmental bioburden when placed into MICU patient rooms. In this study, patients admitted to MICU rooms with CuS were significantly less likely to develop HAIs or to acquire MRSA or VRE compared to those admitted to rooms without CuS. This suggests that environmental bioburden contributes substantially to risk of HAI in the MICU and that by reducing bioburden (through placement of CuS) this risk can be significantly lowered. Clinical Research: Junior Faculty Corresponding Author: Cassandra Salgado, MD, MS Email: salgado@musc.edu Clinical Junior Faculty В Poster #86 ОІ3 integrin/PDGF receptor synergistic signaling mediates cardiac fibrosis in a mouse model of pressure overload hypertrophy Balasubramanian, Sundaravadivel, Harinath Kasiganesan, Lakeya Quinones, Amy Bradshaw and Dhandapani Kuppuswamy Dept. of Medicine/Cardiology, Medical University of South Carolina, Charleston, SC. The precise role of integrins in the process of cardiac fibrosis is not well understood. We hypothesized that upon cardiac hypertrophic stimulation, the synergistic activation of ОІ3 integrin and platelet-derived growth factor receptor (PDGFR) leading to nonreceptor tyrosine kinase (NTK) signaling in cardiac fibroblasts contributes to fibrosis. In response to pressure-overload induced by transverse aortic constriction (TAC), ОІ3 integrin knockout (ОІ3 KO) mice exhibited reduced fibrillar collagen, fibronectin, and fibroblast specific protein (FSP1) levels in comparison to wild-type (WT) mice. Isolated cardiac fibroblasts (Cfb) from ОІ3 KO mice exhibited a reduction in cell adhesion and spreading as well as PDGF-induced cell proliferation and migration when compared to Cfb from WT mice. Next, we analyzed the phosphorylation state of PDGFR and NTK upon PDGF stimulation in Cfb. Our data indicated a marked reduction in the activation of PDGFR, Pyk2, Src and FAK in ОІ3 KO Cfb when compared to WT Cfb. These data suggest that ОІ3 integrin provides a necessary co-stimulation for fibrotic signaling in Cfb. Furthermore, our studies in the mouse TAC model where dasatinib, an inhibitor of PDGFR and NTK, was administered via a mini-osmotic pump, exhibited a preserved ventricular geometry and function and reduced fibrosis upon 4 wk TAC. NTK inhibition with dasatinib also reduced the proliferation, migration and mitogenic signaling of Cfb. These data indicate that integrin-PDGFR synergism could be a potential target to treat cardiac fibrosis. Presenter: Sundaravadivel Balasubramanian, PhD Category: Basic Sciences, Junior Faculty Basic Junior Faculty Poster #87 В Cytoskeletal Role in Protection of the Failing Heart by Beta-Adrenergic Blockade Cheng, Guangmao, Harinath Kasiganesan, Catalin F. Baicu, J. Grace Wallenborn, Dhandapani Kuppuswamy and George Cooper, IV Gazes Cardiac Research Institute, Cardiology Division, Department of Medicine, Medical University of South Carolina and the Department of Veterans Affairs Medical Center. Charleston, South Carolina 29401 Abstract: Formation of a dense microtubule network that impedes cardiac contraction and intracellular transport occurs in severe pressure overload hypertrophy. This process is highly dynamic, since microtubule depolymerization causes striking improvement in contractile function. A molecular etiology for this cytoskeletal alteration has been defined in terms of type 1 and type 2A phosphatase-dependent site-specific dephosphorylation of the predominant myocardial microtubule-associated protein, MAP4, which then decorates and stabilizes microtubules. This persistent phosphatase activation is dependent upon ongoing upstream activity of p21-activated kinase-1, or Pak1. Because cardiac ОІ-adrenergic activity is markedly and continuously increased in decompensated hypertrophy, and because ОІ-adrenergic activation of cardiac Pak1 and phosphatases has been demonstrated, we asked here whether the highly maladaptive cardiac microtubule phenotype seen in pathological hypertrophy is based on ОІadrenergic overdrive and thus could be reversed by ОІ-adrenergic blockade. The data in this study, which was designed to answer this question, show that such is the case. That is, ОІ1- (but not ОІ2-) adrenergic input activates this pathway, which consists of Pak1 activation, increased phosphatase activity, MAP4 dephosphorylation, and thus the stabilization of a dense microtubule network. These data were gathered in a feline model of severe RV pressure overload hypertrophy in response to tight pulmonary artery banding (PAB) in which a stable, two fold increase in RV mass is reached by 2 wk after pressure overloading. Following 2 wk of hypertrophy induction, these PAB cats during the following 2 wk either had no further treatment or had ОІ-adrenergic blockade. The pathological microtubule phenotype and the severe RV cellular contractile dysfunction otherwise seen in this model of RV hypertrophy (PAB No Treatment) was reversed in the treated (PAB ОІ-Blockade) cats. Thus, these data provide both a specific etiology and a specific remedy for the abnormal microtubule network found in some forms of pathological cardiac hypertrophy. Basic Junior Faculty В Poster #88 В Racial/Ethnic Disparities in Access to VA Services As a Pathway to Mortality Differentials Among Veterans Diagnosed with TBI Dismuke, Clara E., PhD, Center For Disease Prevention and Health Interventions for Diverse Populations, Department of Veterans Affairs and Center For Disparities Research, Medical University of South Carolina. Carrae Echoles, MS, Center For Disease Prevention and Health Interventions for Diverse Populations, Department of Veterans Affairs. Mulugeta Gebregziabher,PhD, Department of Medicine, Medical University of South Carolina Leonard E. Egede, MD, MS, Center For Disease Prevention and Health Interventions for Diverse Populations, Department of Veterans Affairs and Center For Disparities Research, Medical University of South Carolina Background: The VA health care system has been proposed as a potential health reform model in the US. Even so, there is recent evidence of racial/ethnic disparities in mortality among Veterans diagnosed with Traumatic Brain Injury (TBI). This study examines the association of race/ethnicity and utilization as a moderator of the association of race/ethnicity with mortality among Veterans with TBI. Methods: The study examined a national cohort study of 7,885 Non-Hispanic White, 1,748 NonHispanic Black, 314 Hispanic, and 4,743 other/missing race/ethnicity Veterans clinically diagnosed with TBI between January 1, 2006 and December 31, 2006 in VA medical centers and community based outpatient clinics. All Veterans were followed from January 1, 2006 through December 31, 2009 or until date of death. Utilization was tracked for 12 months. Comorbidity adjusted mortality was compared by race/ethnicity using cox regression while service access was compared using logit regression analysis. Results: Overall mortality at 48 months was 6.7% in Hispanic, 2.9% in Non-Hispanic White, and 2.7% in Non-Hispanic Black Veterans. In a mortality model adjusting for demographic and comorbid conditions, Hispanic ethnicity was associated with a higher likelihood of mortality. However, upon including utilization, race/ethnicity was no longer significant. In access models adjusting for race/ethnicity, Hispanic ethnicity was associated with a higher likelihood of not accessing TBI clinic (HR 2.21; 95% CI 1.40:3.49), neurology (HR 2.18; 95% CI 1.38:3.45), imaging (HR 2.40; 95% CI 1.53:3.75), mental health (HR 2.46: 95% CI 1.57:3.85) and rehabilitation (HR 2.32; 95% CI 1.49:3.63) services in VA hospitals and clinics. Conclusions: Racial/ethnic disparities in access to services account for racial/ethnic disparities in mortality rates among Veterans diagnosed with TBI. Further research is needed to identify interventions which may improve access to VA services for minority Veterans. Acknowledgement: We acknowledge and appreciate the resources provided by the Center for Disease Prevention and Health Interventions for Diverse Populations HSR&D program (grant REA 08-261) and the Ralph H. Johnson Veterans Affairs Medical Center. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. Basic Junior Faculty В Poster #89 Remodeling of the Peripheral Cardiac Conduction System in Response to PressureOverload. Harris PhD, Brett S1, Catalin F Baicu, PhD2, Nicole Haghshenas MS1, Harinath Kasiganesan PhD2, Mary S Rackley, BS2, Rupak Mukherjee, PhD3, Terrence X O'Brien, MD1,2,4. Departments of Regenerative Medicine and Cell Biology1, Medicine 2 and Cardiothoracic Surgery3, Medical University of South Carolina; Ralph H. Johnson Veterans Administration Medical Center4, Charleston, SC. How chronic pressure-overload affects the Purkinje fibers of the ventricular peripheral conduction system (PCS) is not known. Here, we employ a Connexin40 knock-out/Enhanced Green Fluorescent Protein knock-in transgenic mouse model to specifically label the PCS. We hypothesized that the subendocardially-located PCS would remodel following chronic pressureoverload and therefore analyzed cell size, markers of hypertrophy as well as PCS-related ion channel expression patterns. Left ventricular hypertrophy with preserved systolic function was induced by 30 days of surgical trans-aortic-constriction (TAC). After TAC, we observed that PCS cardiomyocytes hypertrophied by 23% (p<0.05) and that micro-dissected PCS tissue exhibited upregulated markers of hypertrophy. PCS cardiomyocytes showed a 98% increase in the number of Connexin40 positive gap junction particles with an associated two-fold increase in gene expression (p<0.05). In addition, we identified a 50% reduction in Connexin43 gap junction particles located at the interface between the PCS and the working cardiomyocytes. Finally, we measured a four-fold increase of the ion channel, HCN4, throughout the PCS (p<0.05). These novel findings characterize PCS cardiomyocyte hypertrophy after chronic pressureoverload. We identified significant hypertrophic growth accompanied by remodeling of three key ion channels within PCS cardiomyocytes. Our findings provide proof-of-concept that pressure-overload induces specific cellular changes, not just within the working myocardium but also within the specialized PCS. Corresponding Author: Brett S. Harris Type of Research: Basic Science Junior Faculty Email: harrisbs@musc.edu Basic Junior Faculty Poster #90 Effect of HDAC Inhibitor Treatment on Left Ventricular Contractile Dysfunction in Coronary Artery Occlusion Induced Myocardial Infarction. Kasiganesan Harinath, Ludivine Renaud, Santhosh K Mani, Donald R Menick Research Assistant Professor, Gazes Cardiac Research Institute Coronary heart disease, which is the single largest cause of cardiovascular disease, is the narrowing of arteries over time caused by atherosclerotic plaques or the acute occlusion of the coronary artery by thrombosis, both of which lead to myocardial infarction (MI), which leads to contractile dysfunction and heart failure. Protection from coronary heart diseaseвЂ“induced damage of the myocardium during MI injury has been a target of investigation for the development of innovative cardioprotective therapies. Histone deacetylases (HDACs) are a class of enzymes that affect the transcriptional regulation of genes during pathological conditions. Diverse cellular functions are regulated by changes in acetylation status of histones and non histone proteins. Tricostatin-A (TSA) is an antifungal antibiotic with cytostatic and antiproliferation properties and has been shown to block adverse cardiac remodeling and inflammation via inhibition of HDACs. The present goals were to a) develop a simple and effective in vivo myocardial infarction model linking coronary artery occlusion mediated contractile dysfunction and heart failure, b) test the hypothesis that TSA prevents these pathophysiological changes occurring during myocardial infarction. Four groups of CD1 mice (N=10) aged 5 months were randomly selected for the study. The group 1 served as non treatment controls. Group 2 received vehicle twice a day intraperitoneally for 3 weeks. Group 3 received TSA at the dose of 1 mg/kg twice a day for 3 weeks and also served as sham control for the MI group. Group 4 received TSA 12 hrs before surgery and underwent MI surgery and the TSA treatment was continued for 21 days. The left ventricular mass and cardiac systolic and diastolic functions were assessed using two dimensional echocardiography in all the groups before and after a 21 day study period. Initial results show TSA treatment at the dose of 1mg/kg is effective in preventing the deterioration in cardiac function in 3 wk MI mice. Corresponding Author: Harinath Kasiganesan Email: harinath@musc.edu Basic Junior Faculty Poster #91 Histone Deacetylase Inhibitor Suppresses Matrix Metallo Proteinase-1and Protects the Retina. Mani, Santhosh K1, Craig E Crosson2, Michelle Haracznak2, Ludivine Renaud and Donald R. Menick1. 1 Gazes Cardiac Research Institute, Department of Medicine, 2Deparment of Opthomology, MUSC. Protein acetylation is an essential mechanism for regulating transcriptional cell signaling and inflammatory events. The current studies investigate if reduced histone deacetylase (HDAC) activity can limit ischemic retinal injury. Glaucoma is a common cause of blindness affecting approximately 2% of Americans over the age of 40 and over 60 million people worldwide. Studies have provided evidence that dysfunction within retinal ganglion cell bodies, photoreceptors, lateral geniculate nucleus or visual cortex can contribute to the pathogenesis of glaucomatous optic nerve degeneration; however, it is changes within the lamina cribrosa of the optic nerve head that are thought to play the central role in this disease. Previous studies have provided evidence that the secretion and activation of matrix metalloproteinases (MMPs) from astrocytes contribute to retinal damage induced by inflammation, and ischemic injury. The purpose of these studies was to investigate the impact of histone deacetylase (HDAC) inhibitors on MMP expression induced by the inflammatory cytokine TNFО±. To stimulate MMP secretion, cultured primary human astrocytes were incubated with TNFО± (10 ng/ml) for 24 hours. Cells were pretreated with HDAC inhibitor trichostatin A (TSA,100 nM) for 1 hour prior to the addition of TNFО± to investigate the role of HDACs. The secretion of MMP-1 and histone H4 acetylation were determined by Western blot analysis. The addition of TNFО± for 24 hours significantly increased the secretion of MMP-1 over control levels, by 270%. Pretreatment with TSA blocked the TNFО±-induced secretion of MMP-1. The MMP-1 promoters contain AP1, STAT1 and NFОєB consensus elements, which are critical to MMP induction in response to cytokines and proinflammatory stimuli. TSA treatment does not significantly disrupt either the NFОєB or AP1 activating pathways in human astrocytes. Importantly, TNFО± induces the activation of the JAK/STAT1 pathway, which was completely inhibited by TSA treatment. In addition pre-treatment of astrocytes with the JAK1/2 inhibitor AG 490 inhibited TNFО±stimulated expression of MMP-1 and MMP-3. These data provide evidence that the JAK/STAT pathway is critical for TNFО±- stimulated upregulation of MMP-1 and MMP-3 in optic nerve head astrocytes and the activation of this pathway is inhibited by TSA treatment. Further studies elucidate that SOCS1 acetylation plays an important role in the regulation of MMP-1 expression. Hence, protein acetylation/deacetylation may represent a central step in the JAK/STAT mediated secretion of MMPs from optic nerve astrocytes, and the use of HDAC inhibitors may provide a novel approach for the treatment of optic neuropathies. Type of Research: Basic Research Email: manis@musc.edu. Basic Junior Faculty Poster #92 Efficacy of Transcranial Direct Current Stimulation (tDCS) and Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Fibromyalgia Syndrome: A Systematic Review Marlow MSPH, Nicole M.1; Heather S. Bonilha, PhD, CCC-SLP2; E. Baron Short, MD, MSCR3 1 Corresponding author: Research Associate (Faculty), Medical University of South Carolina (MUSC), Dept. of Medicine, Div. of Biostatistics and Epidemiology, Charleston, SC, marlownm@musc.edu 2 MUSC, Dept. of Health Sciences and Research 3 MUSC, Dept. of Psychiatry and Behavioral Sciences SUBJECT: Comparative Effectiveness Research OBJECTIVE: To systematically review the literature to date applying repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) for patients with fibromyalgia syndrome (FMS), summarizing procedures (including brain site, frequency, intensity, duration, total sessions, scheduling), FMS symptom outcomes, and levels of evidence. METHOD: Electronic bibliography databases screened included PubMed, Ovid MEDLINE, PsychINFO, CINAHL, and Cochrane Library. The keyword вЂњfibromyalgiaвЂќ was combined with (вЂњtranscranialвЂќ and вЂњstimulationвЂќ) or вЂњTMSвЂќ or вЂњtDCSвЂќ or вЂњtranscranial magnetic stimulationвЂќ or вЂњtranscranial direct current stimulationвЂќ. Reference sections of studies meeting inclusion criteria were screened for relevant publications. RESULTS: Nine of 23 studies were included, 5 each for rTMS (high-frequency M1 = 2, low-frequency DLPFC = 2, high-frequency DLPFC = 1) and tDCS (anodal-M1 = 1, anodal-M1/DLPFC = 3). Eight were double-blinded randomized clinical trials. Outcomes reviewed included pain, quality of life, tender points, depression, adverse events, and drop-outs. Most (80%) rTMS studies with pain outcome results reported significant decreases, while all tDCS studies with pain outcome results reported significant decreases. Greater longevity of pain reductions was observed for excitatory M1 rTMS/tDCS. Completion rates ranged from 80% to 100% for active-stimulation groups, much higher than such results reported in the literature for FDA approved FMS pharmaceuticals. CONCLUSION: Excitatory rTMS/tDCS at M1 may play a vital role among multidisciplinary treatment components for FMS, particularly for patients who are unable to find adequate symptom relief with other therapies. Further work into optimal stimulation parameters and standardized testing methodologies are needed to clarify the efficacy and effectiveness of these neuromodulation techniques for treating fibromyalgia. ACKNOWLEDGEMENTS: Financial support provided by the NIH/NIAMS P60 Grant AR049459 and NIH KL2 Award RR029880 as well as the MUSC Div. of Biostatistics and Epidemiology, Dept. of Healthcare Leadership, Dept. of Health Sciences and Research, and Dept. of Psychiatry and Behavioral Sciences. We are also most grateful for the exceptional mentorship provided by Charles Ellis, PhD, CCC-SLP, Kit N. Simpson, DrPH, and Richard M. Silver, MD. Basic Junior Faculty Poster #93 Angiotensin II Induces Cyclooxygenase 2 (COX-2) Expression in Rat Aorta Vascular Smooth Muscle Cells via AT1A Receptor Internalization and the NF-ОєB Pathway. Morinelli, Thomas A. 1, Linda P. Walker1 and Michael E. Ullian1,2 1 2 Division of Nephrology, Department of Medicine, Medical University of South Carolina and the Ralph H. Johnson VA Medical Center, Charleston, SC ABSTRACT: Activation of the angiotensin II (AngII) AT1A receptor (AT1AR) in rat aorta vascular smooth muscle cells (RASMC) results in the propagation of multiple intracellular signaling pathways including increased protein synthesis. One such protein is the pro-inflammatory enzyme cyclooxygenase 2 (COX-2). We have previously shown that nuclear localization of an internalized AT1AR results in activation of transcription of the gene for COX-2, PTGS-2. Others have suggested that AngII stimulation of COX-2 protein synthesis is mediated by NFв€’ОєB. In the present study we utilized three different inhibitors of the NFв€’ОєB pathway, each targeting a specific aspect of NFв€’ОєB activation to characterize the role between AT1aR activation, NFв€’ОєB and AngII-induced COX-2 synthesis. Ro-1069920 and parthenolide, agents which inhibit NFв€’ОєB by blocking proteosomal degradation of IОє BО±, blocked p65 NFв€’ОєB nuclear localization, AngII-induced COX-2 protein expression and inhibited AT1AR internalization, without inhibiting AngII-induced p42/44 ERK activation. Curcumin, an inhibitor of interaction of NFв€’ОєB with NFв€’ОєB /DNA recognition motifs and blocking NFв€’ОєB induced transcription, blocked AngII-induced COX-2 protein expression, without altering AT1AR internalization and p42/44 ERK activation. Finally, immunoprecipitation and immunoblotting studies show a timedependent AngII stimulated colocalization of AT1AR with p65/ NFв€’ОєB. Taken together, these data demonstrate that activation of the AT1AR by AngII results in colocalization of the internalized receptor with a subunit of the NFв€’ОєB pathway. Interruption of AT1AR internalization by specific NFв€’ОєB inhibitors results in a loss of the ability of AngII to increase the synthesis of the pro-inflammatory enzyme COX-2, thereby linking the internalization of the receptor with the NFв€’ОєB pathway. CATEGORY: Basic Research Faculty CORRESPONDING AUTHOR: Thomas A. Morinelli, Ph.D. EMAIL: morinelt@musc.edu Basic Junior Faculty Poster #94 В Neuropilin-2 is upregulated during EMT in lung cancer Nasarre, Patrick, Joelle Roche, Vincent Potiron, Joyce Nair-Menon, Robert Gemmill and Harry Drabkin Division of Hematology-Oncology, Department of Medicine, MUSC Neuropilins (NRP1 and NRP2) are high affinity receptors for the class-3 semaphorins, cell guidance molecules involved in tissue development, immune responses, angiogenesis and cancer. Semaphorins affect cell protrusion, spreading and adhesion, and can trigger migratory responses often in a repulsive manner depending on the cellular context. Interestingly, neuropilins are also receptors for galectin-1 and growth factors including VEGF, PlGF, EGF and TGFОІ. We previously cloned the SEMA3F gene from chromosome 3p21.3, which undergoes homozygous deletion and frequent loss of heterozygosity in lung cancer. We found that SEMA3F levels were inversely correlated with tumor aggressiveness in human lung cancer and confirmed its tumor suppressor activity in experimental xenograft models. We subsequently discovered that SEMA3F is directly downregulated by ZEB1, a transcription factor involved in the epithelial to mesenchymal transition (EMT). In the present study, we asked whether SEMA3F specific receptor, NRP2, was also regulated during the EMT process. TGFОІ, a physiologic EMT inducer, stimulated NRP2 expression in two NSCLC cell lines. Forced expression of ZEB1, but not Snail, also induced NRP2. Conversely, ZEB1 and Snail inhibition blocked NRP2 upregulation by TGFОІ. Importantly, inhibiting NRP2 or ZEB1 expression reduced TGFОІ-induced migration in an equivalent manner. In lung cancer tissue microarrays, NRP1 and NRP2 were preferentially expressed in the tumor compartment, whereas the EMT-related transcription factors, ZEB1 and Snail, were predominantly expressed in the stroma. Of note, NRP2 was also expressed in stromal cells and was significantly associated with both ZEB1 and a higher (worse) tumor grade. Since NRP2 is the highest affinity receptor for SEMA3F, our results suggest that loss of SEMA3F coupled with increased NRP2 would facilitate the binding of growth factors to NRP2 to further promote EMT and metastasis. Therefore, targeting NRP2 could be an important therapeutic approach against EMT in lung cancer. Corresponding Author: Patrick Nasarre, Assistant Professor Type of Project: basic Email: nasarre@musc.edu Basic Junior Faculty В Poster #95 В Targeting the amino acid transporter xCT inhibits progression of lymphoma associated with an oncogenic herpesvirus in vivo Zhiqiang, Qin1,2, Lu Dai1,3, Bryan P. Toole3 and Chris Parsons1,2 Departments of Medicine1, Craniofacial Biology2, and Regenerative Medicine & Cell Biology3, Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas St., Charleston, SC 29425 Abstract: The KaposiвЂ™s sarcoma-associated herpesvirus (KSHV) is the causative agent of primary effusion lymphoma (PEL)вЂ”an aggressive malignancy associated with HIV/AIDS that portends near 100% mortality within 6-12 months from the time of diagnosis despite control of HIV infection and standard chemotherapy. The amino acid transporter, xCT, exchanges intracellular glutamate for extracellular cystine at the cell membrane, resulting in restoration of intracellular glutathione (GSH) and protection of cancer cells from oxidative stress-induced cell death. Initial screening of human tumors revealed that xCT is readily expressed on the cell surface of two patient-derived, KSHV-infected PEL cell lines (BCP-1 and BCBL-1). Two commercially available compounds, monosodium glutamate (MSG) and sulfasalazine (SUL), inhibit amino acid exchange through xCT. Initial functional studies demonstrated that MSG and SUL induced caspases-mediated apoptosis for PEL cells. Subsequent studies revealed that incubation of PEL cells with either MSG or SUL reduced intracellular GSH content and increased intracellular reactive oxygen species (ROS) while suppressing phosphorylation of intracellular signaling molecules critical for PEL cell survival, including PI3K/Akt, MAPK and NF-ОєB. Finally, using an established murine model for PEL, we have demonstrated that systemic administration of SUL significantly reduces PEL tumor growth in vivo. Collectively, these data identify xCT as an important determinant of PEL cell survival and support evaluation of SUL as an adjunctive therapeutic agent for PEL in clinical trials. Category: Junior Faculty (Zhiqiang Qin), Basic Science E-mail: qinzh@musc.edu. Basic Junior Faculty В Poster #96 В Association of reactive intermediate genes with systemic lupus erythematosus (SLE) varies across populations with different African ancestries Ramos,В В Paula S.1, James C. Oates1, Diane L. Kamen1, Patrick M. Gaffney2, Carl D. Langefeld3, Jennifer A. Kelly2, Kenneth M. Kaufman4, Robert P. Kimberly5, Timothy B. Niewold6, Chaim O. Jacob7, Betty P. Tsao8, Elizabeth E. Brown9, Michelle Petri10, Rosalind Ramsey-Goldman11, John D. Reveille12, Luis M. Vila13, Judith A. James2, Joel Guthridge2, Joan T. Merrill14, Susan A. Boackle15, Barry I. Freedman16, Hal Scofield2, Anne M. Stevens17, Timothy J. Vyse18, Lindsey A. Criswell19, Kathy L. Moser2, Marta E. AlarcГіn-Riquelme20, John B. Harley4, Gary S. Gilkeson1 1) Division of Rheumatology and Immunology, Department of Medicine, Medical University of South Carolina, Charleston, SC; 2) Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK; 3) Wake Forest School of Medicine and Center for Public Health Genomics, Winston-Salem, NC; 4) Division of Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; 5) Department of Medicine, University of Alabama at Birmingham, Birmingham, AL; 6) Section of Rheumatology and Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL; 7) Keck School of Medicine, University of Southern California, Los Angeles, CA; 8) David Geffen School of Medicine, UCLA, Los Angeles, CA; 9) Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL; 10) Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; 11) Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL; 12) Rheumatology and Clinical Immunogenetics, University of Texas Health Science Center at Houston, Houston, TX; 13) Department of Medicine, Division of Rheumatology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico; 14) Clinical Pharmacology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK; 15) Division of Rheumatology, University of Colorado Denver, Aurora, Colorado; 16) Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC; 17) Division of Rheumatology, Department of Pediatrics, University of Washington, Seattle, WA; 18) Division of Genetics and Molecular Medicine, KingвЂ™s College, London, United Kingdom; 19) Rosalind Russell Medical Research Center for Arthritis, University of California, San Francisco, CA; 20) Center for Genomic and Oncological Research, Universidad de Granada, Granada, Spain. ABSTRACT BODY Very little is known about the genetic etiology of systemic lupus erythematosus (SLE) in individuals of African ancestry вЂ“ in spite of its higher prevalence, incidence, disease severity, and mortality rates in African Americans (AA). Overproduction of nitric oxide (NO) has been implicated in its pathogenesis and correlated with disease severity, making NO synthases and other reactive intermediate genes biological candidates for disease susceptibility. Here, we report the first comprehensive analysis of reactive intermediate genes for their association with SLE in populations of African ancestry. One such population is the Gullah of the Sea Islands of South Carolina: a population isolate with reduced admixture and genetic heterogeneity, which may increase the power to detect associations in this population. We analyzed 279 SNPs from 55 regions in 133 Gullah cases and 112 Gullah controls, as well as in other 1432 AA cases and 1575 AA controls. These and approximately 300 additional ancestry informative markers were genotyped on an Illumina custom array; principal components analysis and admixture estimates were computed and adjusted for in association analyses. While the glutathione reductase GSR (rs2253409, P=0.0014, odds ratio (OR) [95% confidence interval (CI)]=1.26 [1.09-1.44]) and paraoxonase PON3 (rs17879114, P=0.0016, OR [95%CI]=0.79 [0.68-0.91]) were the most significant single-SNP associations in AA, in the Gullah the NADH dehydrogenase NDUFS4 (rs381575, P=0.0065, OR [95%CI]=2.10 [1.23-3.59]) and nitric oxide synthase NOS1 (rs561712, P=0.0072, OR [95%CI]=0.62 [0.44-0.88]) were the most strongly associate with SLE. When analyzed together, GSR remained the most significant effect (rs2253409, P=0.00072, OR [95%CI]=1.26 [1.10-1.44]). Haplotype and two-loci interaction analyses also uncovered different loci in each population. These results suggest that the patterns of association are distinct and specific loci may be more strongly associated in specific populations of African ancestry. Basic Junior Faculty В Poster #97 В Deregulation of ceramide chain-length composition affects trafficking and Golgi morphology Spassieva, Stefka D.1, * and Lina M. Obeid1,2 1 Department of Medicine, Division of General Internal Medicine/Geriatrics, Medical University of South Carolina, Charleston, SC, 29425, 2Ralph H. Johnson Veterans Administration Hospital, Charleston, South Carolina, 29401 In the recent years, the research on ceramide was focused on its role as a second messenger in regulating cell death. Next to its role as a second messenger, ceramide is a building block of the biological membranes and precursor of complex sphingolipids. Ceramide consists of a group of molecules, which can differ in the chain-length of their fatty acid moiety. The chain-length of the fatty acid of a ceramide influences its biophysical properties, but the significance of that for cellular homeostasis is largely unknown. In our current project we investigated how decreased synthesis of very long-chain (VLC) ceramides (C22, C24) affected membrane trafficking and Golgi organization. For that purpose, we down regulated the enzyme responsible for VLC ceramides, ceramide synthase 2 (CerS2), by siRNA in cancer cells and applied cell biology approach to investigate membrane trafficking and Golgi morphology. Our results showed that down-regulation of VLC ceramide synthesis led to over compensatory production of shorter chain-length (C14, C16) ceramides. Confocal analysis with ceramide antibody showed abnormal intracellular ceramide distribution in the treated cells compared to control. In addition, we followed the trafficking of the temperature sensitive vesicular stomatitis virus G (VSVG) вЂ“GFP fusion protein in cells with down-regulated VLC ceramide synthesis and in controls. The results showed delay in VSVG-GFP trafficking in the cells with disrupted VLC ceramide synthesis. Moreover, confocal and electron microscopy analyses revealed abnormal Golgi morphology in cells with disrupted VLC ceramide synthesis. * Corresponding author: spassisd@musc.edu Basic Junior Faculty В