Recent Submissions

  • An Iterative Procedure to Select and Estimate Wavelet-Based Functional Linear Mixed-Effects Regression Models

    Lundeen, Jordan Sarah; Biostatistics (Augusta University, 2019-12)
    Actigraphy is the continuous long-term measurement of activity-induced acceleration by means of a portable device that often resembles a watch and is typically worn on the wrist. Actigraphy is increasingly being used in clinical research to measure sleep and activity rhythms that might not otherwise be available using traditional techniques such as polysomnography. Actigraphy has been shown to be of value when assessing circadian rhythm disorders and sleep disorders and when evaluating treatment outcomes. It can provide more objective information on sleep habits in the patient's natural sleep environment than using the patient's recollection of their activity or a written sleep diary. We propose a wavelet-based functional linear mixed model to investigate the impact of functional predictors on a scalar response when repeated measurements are available on multiple subjects. The advantage of the proposed model is that each subject has both individual scalar covariate effects and individual functional effects over time, while also sharing common population scalar covariate effects and common population slope functions. An iterative procedure is used to estimate and select the fixed and random effects by utilizing the partial consistency property of the random effect coefficients and selecting groups of random effects simultaneously via the smoothly clipped absolute deviation (SCAD) penalty function. In the first study of its kind, we compare multiple functional regression methods through a large number of simulation parameter combinations. The proposed model is applied to actigraphy data to investigate the effect of daily activity on Hamilton Rating of Depression Scale (HRSD), Insomnia Severity Index (ISI) and Reduced Morningness- Eveningness Questionnare (RMEQ) scores.
  • Acquiring Situation Awareness through Hand-Off in a Critical Care Environment

    Holden, Tina; Nursing (Augusta University, 2019-12)
    Hand-off communication is associated with 80% of hospital errors. Situation awareness (SA) has been targeted as a strategy to reduce errors and enhance patient safety when providing hand-off communication. Few studies have focused on the influence of SA in hand-off communication in the intensive care unit where the risk of errors is high. The purpose of this study was to develop a substantive theory of critical care nursing hand-off. The study was guided by Endsley’s SA framework. A qualitative study design using Straussian grounded theory methods was used to develop a substantive theory related to critical care nursing hand-off. Data collection strategies included observation of 20 critical care nursing hand-offs followed by 34 semi-structured interviews and took place from 2017 to 2019 in a medical and surgical ICU at two academic tertiary care facilities. Data analysis was conducted using constant comparative analysis and was guided by Endsley’s model of SA. Results revealed that hand-off is a basic social process with a core category of handing-off awareness. The process contained four phases: interactive, reflective, maintenance, and preparatory. The interactive phase was characterized by communication between the giver and receiver of hand-off. During that phase, the 10 critical elements of hand-off were passed on to the receiver. These critical elements included the code status, past medical history, story, systems assessment, trends, changes, rationale, level of organ support, and anticipation. Handing off these elements in a way that flows with logical order affects awareness. Nursing behaviors of the giver associated with handing off awareness are linked to the critical elements. For the receiver, these behaviors include arriving prepared, reporting the critical elements, controlling flow, and making connections between the critical elements. Behaviors for the receiver include being an active listener, validating information, and asking questions within the flow of information. In the reflective phase, the resilient nurse bridges gaps in awareness. The maintenance phase is characterized by nursing actions that support hand-off information recall. In the maintenance phase, SA is maintained through artifacts. Artifacts are tools used by nurses to aid in the cognitive function of hand-off. The preparatory phase is characterized by information synthesis and organization. The four phases of hand-off are re-occurring and are influenced by individual and organizational factors. Individual factors include a nurse’s personal process, experience, socialization, and emotional intelligence. Organizational factors include unit policies, unit artifacts, and safety culture. Theory and research implications include the need for future research to further expand the framework of SA in hand-off, the use of qualitative methods to provide insight into complex areas of healthcare, and the need for educational interventions on SA hand-off. Practice implications include evaluation of current hand-off practices in the ICU and evaluation of organizational influences on hand-off. The study concludes that the theory of handing-off awareness in the ICU is a continuous process that occurs over four phases in a repetitive cycle that starts again with each shift change. The critical elements, flow, nursing behaviors, time, and external factors influence the ability of the nurse to achieve optimal SA.
  • Evaluating the Impact of High Fidelity Patient Simulation on Clinical Reasoning in Undergraduate Nursing Students

    Gee, Rebecca Mathews; Nursing (Augusta University, 2019-12)
    Introduction: Graduate nurses must enter nursing with clinical reasoning skills that will allow them to appropriately care for patients. With limited clinical sites, nurse educators are challenged to graduate clinically-competent nurses who possess clinical reasoning skills that will allow them to appropriately care for patients. The use of high fidelity patient simulation (HFPS) as an adjunct to clinical experiences may be a solution, but previous studies have shown limited evidence that HFPS improves clinical reasoning in nursing students. A variety of tools have been used to measure clinical reasoning (or one of its components). However, most of them were not specific to nursing. Without a consistent, nursing-specific tool, exploration of HFPS effects on clinical reasoning skills is challenging. The Nursing Specific Script Concordance Test (NSSCT), a validated nursing-specific tool measuring clinical reasoning, was used for this study. The purpose of this study was to examine the impact of HFPS on the clinical reasoning skills of first-semester, pre-licensure, Bachelor of Science in Nursing (BSN) students. Two specific aims were explored: 1) determine whether teaching with HFPS scenarios improved the clinical reasoning skills of pre-licensure, first semester BSN students, and 2) determine whether the NSSCT detected a significant difference in NSSCT mean scores before and after HFPS scenarios. Methods: This study used a two-group, randomized crossover design with 14 first-semester, pre-licensure, BSN students (n = 8; n = 6). Each participant took a baseline NSSCT, followed by the experimental group participating three simulation scenarios and the control group participating in the standard curriculum only. Then a second NSSCT was administered to each participant. Then, the control group participated in the three simulation scenarios while the experimental group participated in the standard curriculum only. Then, a third NSSCT was administered. NSSCT mean scores were compared between and within the groups after each administration. Results: There were no statistical differences (p = 0.494) in mean NSSCT scores in pre-licensure, first-semester, BSN, students after participating in HFPS scenarios, inferring that in this sample, HFPS did not significantly increase clinical reasoning. There were no statistical differences in mean NSSCT scores (p = 0.064) between the control group and experimental group after the second NSSCT administration, suggesting that the clinical reasoning skills were not different between students who completed the three simulation scenarios versus students who participated in the standard curriculum alone. Finally, there were no statistical differences (p = 0.596) between the control group and experimental group after all participants completed the three simulation experiences. Conclusions: The results from this study did not conclude that HFPS improved clinical reasoning in first-semester, pre-licensure, BSN students. However, due to the limitations of this study (small sample size [n = 14], test/retest reliability, and history) a replication study with modifications should be considered to fully examine the effect of HFPS on clinical reasoning in pre-licensure, BSN students.
  • CHOLINESTERASE INHIBITOR TOXICITY: MECHANISTIC STUDIES AND THERAPEUTIC STRATEGIES FOCUSED ON AXONAL TRANSPORT

    Naughton, Sean X; Biomedical Sciences (Augusta University, 2019-12)
    Organophosphates (OPs) are a broad class of chemicals with a variety of uses that include pesticides, chemical warfare agents, fuel additives, and plasticizers. Due to their sheer number of applications and known toxicological profile, OPs represent a persistent concern to human health worldwide. Furthermore, the effects of OPs that occur independently of their well-known mechanism of acute toxicity (AChE inhibition) have not been well studied. The presented research seeks to expand upon our understanding of AChE-independent mechanisms of OP toxicity as well as to identify potential therapies for treating these negative effects. In Manuscript 1 we demonstrate that the OP diisopropylfluorophosphate (DFP) induced axonal transport deficits occur in vivo at exposure levels that were not associated with cholinergic toxicity. Additionally, we observed deficits in white matter integrity following sub-acute DFP exposure. In Manuscript 2 we present a series of experiments, which were conducted to identify potential therapeutic compounds for the treatment of OP induced deficits in axonal transport. Here, we utilized a phenotypic drug-screening assay in order to identify compounds that could be protective against DFP. In Manuscript 3 we present data which demonstrates that the carbamate physostigmine does not impair axonal transport, as has been previously demonstrated with OPs. These experiments were critical to demonstrating the AChE independence of OP-induced axonal transport deficits and further elucidate the unique nature of OP toxicity in comparison to other AChE inhibitors. Collectively, these studies contribute to a better understanding of the full spectrum of toxicological effects of OPs and provide insightful findings into potential therapeutics for the treatment of OP related toxicity.
  • Primary Tumor-Induced Immunity Is Suppressed By Surgery-Induced Inflammation In The Presence Of Residual Tumor Cells

    Piranlioglu, Raziye; Biomedical Sciences (Augusta University, 2019-12)
    It is widely thought that tumor cells disseminate from a primary site into the circulation during the early stages of tumor development. However, the fate of these early disseminated tumor cells (DTCs) has been elusive. By utilizing the murine mammary tumors, 4T1 and EMT6, in a syngeneic mouse model, we show that both tumors disseminate into secondary organs but only 4T1 tumors are able to generate metastasis. In contrast, EMT6 primary tumors induce an anti-tumor response that leads to elimination of DTCs. This anti-tumor immunity is CD8+ T cell-dependent and provides long-term immunity. Furthermore, the mice are free of DTCs within a couple of days when primary tumors are completely resected and they reject subsequently injected tumors, whereas mice with residual tumors following surgery show enhanced local recurrence and outgrowth of DTCs at metastatic sites; this effect may be explained by elevated levels of granulocyte colony-stimulating factor (G-CSF). This increase is accompanied by an accumulation of immature myeloid-derived suppressor cells (MDSCs) in the spleen and lungs, the main target organ for metastasis. Moreover, the infiltration of a granulocytic subset of MDSCs (gMDSCs) leads to a decrease in a subset of T cells that have a role in long-term immunity. Our goal for this study is to elucidate how immune components of distant organs affect the fate of DTCs and the role of surgery induced-inflammation in generating a pre-metastatic niche. Our studies may also provide a molecular explanation of improved overall survival in breast cancer patients following complete resection of primary tumors with negative margins.
  • ROLE OF ARGINASE IN OBESITY-INDUCED VISCERAL ADIPOSE TISSUE DYSREGULATION AND ENDOTHELIAL DYSFUNCTION

    Atawia, Reem T.; Biomedical Sciences (Augusta University, 2019-11-05)
    An obesity epidemic continues to rise worldwide. Visceral (central) obesity is an important concern as it correlates with metabolic and cardiovascular pathologies. Arginase is a ureahydrolase enzyme with two isoforms (A1-cytosolic and A2-mitochondrial). We found that visceral adipose tissue (VAT) from obese WT mice fed a high fat/high sucrose diet (HFHS) showed a significantly higher expression of A2 compared to mice fed normal chow diet (ND). We also observed that A2 expression is upregulated 3-fold in differentiated 3T3- L1 adipocytes exposed to high levels of palmitate and glucose, a mimic of the obese state, compared to control media. Our study focused on the involvement of A2 in obesity associated metabolic and vascular disorders. WT mice and those globally lacking A2 (A2-/-) were fed HFHS or ND for 16 weeks. The HFHS diet-induced increases in body and VAT weights and total adiposity were prevented or reduced in A2-/- mice. In concert, metabolic chamber studies revealed that energy expenditure and fatty acid oxidation rates were significantly higher in A2-/- compared to WT HFHS mice. VAT from A2-/- mice fed HFHS had higher levels of active AMPK-α, the master regulator of fatty acid metabolism, as well as higher adipocyte expression of genes involved in fatty acid β-oxidation and oxidative phosphorylation, along with preserved mitochondrial density compared to WT HFHS. A2 deletion also prevented HFHS-induced fibrous tissue deposition and inflammation in VAT, which contributed to adipocyte metabolic dysfunction. These results indicate that A2 is involved in metabolic dysfunctions. To gain insights into the role of A2 in adipocytes, primary preadipocytes isolated from VAT of A2-/- mice and differentiated in vitro showed increased expression of adiponectin and better mitochondrial function. Adenoviral overexpression of A2 in differentiated 3T3-L1 cells showed impaired mitochondrial function and increased mitochondrial ROS. Obesity-related metabolic disorders increase the risk of cardiovascular diseases, the leading global cause of death. Endothelium-dependent vasorelaxation, impaired by HFHS diet, was significantly preserved in A2-/- mice, but more prominently prevented in A1+/- mice. In conclusion, A2 is critically involved in HFHS-induced obesity, VAT inflammation and metabolic dysregulation. Both A1 and A2 are involved in HFHS-induced vascular endothelial dysfunction.
  • Socio-Economic Factors and Cardiovascular Disease Mortality: A County-Level Analysis of Georgia

    Adepu, Sanjana (Augusta University, 2019-10)
    Background: With over 20,000 deaths (~1 in every 3 deaths) per year, Cardiovascular Disease (CVD) is the leading cause of death in Georgia. Studying the overall impact of multiple socioeconomic factors (SES) on CVD could lead to a better understanding of the determinants of public health. The factors examined in this study include physical inactivity, median household income, health insurance, and air quality. While several studies examine the effects of a single SES factor on CVD, this study analyses multiple SES factors on CVD death rates in Georgia. Methods: County-level socioeconomic factors for Georgia were obtained from The Center for Disease Control and Prevention. A multiple regression model was developed to identify the factors that explain CVD death rates in Georgia. Results: In Georgia, the median household income and annual average ambient concentrations of PM2.5 were the most significant factors. Lower levels of median household income were associated with higher CVD death rates; higher concentrations of PM2.5 were associated with higher CVD death rates. Additionally, leisure-time physical inactivity was marginally significant, which indicates higher percentages of physical inactivity led to higher CVD death rates. Conclusion: Policies that increase median household income and lower annual ambient concentrations may also have secondary benefits to public health and, in particular, cardiovascular disease death rates in Georgia. Future studies could expand upon this analysis by studying the effects of SES on the national level.
  • Small and Dangerous: MicroRNA-21 and Blindness

    Rajpurohit, Shubhra (Augusta University, 2018-12)
    Background: Retinal and choroidal neovascularization (RNV and CNV, respectively) are characterized by the inappropriate growth of retinal capillaries that may progress to retinal scarring, detachment and vision loss. MicroRNAs (miRs) are short noncoding RNAs which have been demonstrated to modulate diverse cellular processes such as cell differentiation, proliferation, and apoptosis. Our group and others have shown that miR-21 plays a crucial role in regulating angiogenesis and neovascularization in retina. We have previously shown that activation of STAT3/miR-21 pathway leads to loss of TIMP3 and activation of MMP2 and MMP9. Increased activity of MMP2 and MMP9 in the ischemic retina has been linked to the proteolytic degradation of pigmented epithelial derived factor (PEDF), a key retinal angiostatic factor. Importantly, miR-21 targets peroxisome proliferator-activated receptor alpha (PPARα). PPARα-responsive elements are found in PEDF promoter suggesting that this could be a potential transcription factor for PEDF. The role of miR-21 in regulating PEDF and PPARα in Human Retinal Pigmented Epithelial cells (HuRPE) has never been investigated and is the main goal of the present study. Methods: HuRPE were treated with VEGF at different time points. Transfection of HuRPE cells was performed using a specific miR-21 inhibitor, a miR-21 mimic, and scrambled miRNA as a negative control. Western blot and real-time PCR were used to evaluate the expression of PEDF and PPARα. Luciferase assay was performed to study the interactions between PPARα and PEDF. Results: VEGF treatment of HuRPE cells promoted the expression of miR-21 while PEDF and PPARα expression was down regulated. Further, overexpression of miR-21 decreased PEDF and PPARα expression. Next, we observed that inhibiting miR-21 expression could rescue VEGF-induced down regulation of PEDF and PPARα. To study the specific relationship between PPARα and PEDF, we treated HuRPE cells with siPPARα (inhibition) or PPARα agonist (fenofibrate) (induction). While, inhibition of PPARα expression decreased PEDF expression, PPARα agonist enhanced PEDF 5 expression. Lastly, using a PEDF promoter plasmid we observed that, PPARα could regulate PEDF expression by modulating its promoter activity. Conclusion: Collectively, our data shows that VEGF-mediates induction of miR-21 expression regulates PPARα-PEDF axis and could have a significant role in choroidal neovascularization. This suggests that miR-21 potentially plays a critical role in age-related macular degeneration.
  • The Effect of Nrf2 on Inflammatory Responses of Human Monocytic Cells After Blue Light Exposure

    Trotter, Leigh Ann; Trotter, Leigh Ann; Department of Oral Biology (12-Apr)
    Blue light treatment alters cellular signaling and affects intracellular biochemical processes in tissues. PURPOSE: This study determined the ability of blue light to modulate Nrf2 and decrease LPS-induced secretion of pro-inflammatory cytokines from cultured, human monocytic cells. METHODS: Cultured THP-1 human monocytic cells were exposed to LPS and blue light treatment. Western Blot analyses, EMSA, and ELISA were used to evaluate NF?B, Nrf2, HO-1, TNF-?, IL-6 and IL-8 production. RESULTS: Light treatment increased nuclear Nrf2 and increased HO-1. Cells pretreated with light had no detectable NF?B-DNA binding. LPS treatment increased nuclear NF?B, and had little effect on Nrf2. Light pre-treatment significantly decreased the amount of TNF-? by 63% and IL-8 by 55%. CONCLUSIONS: Blue light increases the production of Nrf2 and HO-1, decreases the ability of Nf?B to bind in the nucleus, and leads to a decrease in the secretion of pro-inflammatory proteins in human monocytic cells.
  • The role of Toll-like receptor (TLR) 2 in the systemic immune response profile of mice induced to develop squamous cell carcinoma of the upper aerodigestive tract

    El-Shafey, Sally; El-Shafey, Sally; Department of Oral Biology (4/1/2017)
    Background Head and necksquamous cell carcinomais associated with immunosuppression, a state in which the progression of cancer is associated with disturbances in the immune system functions. Emerging studies suggest a fundamental role for the innate immune system, particularly Toll-like receptor 2 (TLR2), in this process.QuestionsIn this study, we investigated the potential roles of TLR2 on systemic immune profile in a mouse model of headand necksquamous cell carcinoma.MethodsTwo different protocols of a mouse model of 4-nitroquinoline 1-oxide and ethanol-induced carcinogenesis to induce head and neck squamous cell carcinoma were used. To evaluate the systemic immune profiles, total RNA wasisolated from the spleens of four groups of animals, including carcinogen-treated and control untreated wild-type and toll-like receptor 2-deficient animals. Quantitative real-time PCR was performed forgenesrepresentative of house-keeping genes, type 1 and type 2 immune responses, regulatory T and B cells, and adenosine receptors.Results and ConclusionIn the standard protocol of 4-nitroquinoline 1-oxide and ethanol-induced carcinogenesis, there was asignificant upregulation of adenosine receptor A2a in the spleens of wild type iiimice treatedwith4-nitroquinoline 1-oxide and ethanolrelative to wild type untreatedanimals. In the standard protocol of carcinogenesis, there was a significant upregulation of CD39 in the spleens of TLR2-koanimalstreated with 4-nitroquinoline 1-oxide and ethanol relative to untreated TLR2-ko mice. These results suggest that carcinogenesis in the upper aerodigestive tract is associated with alterations in the systemic immune profile reflected in the spleen. However, the specific impact on the immune profiles appears to be affected by the presence or absence of TLR2.
  • SUSTAINED RELEASE FORMULATION FOR VASCULAR ENDOTHELIAL GROWTH FACTOR

    Elzinga, Jennifer Lynn; Department of Oral Biology (2/1/2013)
  • EFFECT OF MATRIX-BOUND BISPHOSPHONATES ON MONOCYTE DIFFERENTIATION AND OSTEOCLAST FUNCTION

    Abraham, Pheba; Abraham, Pheba; Department of Oral Biology (5/1/2017)
    This study was to explore the effect of local, matrix-bound bisphosphonates to monocytedifferentiation and osteoclast function in vitro. Experiments were designed using osteoassay plates. Cell-viability, differentiation, resorption pits and gene expression were analyzed to see the effect of matrix-bound BPs on monocyte differentiation and osteoclast function. EDTA was used as a chelating agent to remove the bound BPs. There was a dose dependent response in the differentiation and resorption pits. With chelation, there was increase in differentiation, resorption pits and increase in the calcium and PYD in the supernatant. Thus, matrix-bound Bisphosphonatesare biologically active and they inhibit monocyte differentiation and osteoclast function. Thereby removal of this matrix-bound drug can rescue osteoclast differentiation and function.
  • Inherent Gene Expression and Protein Profile Differences Between Alveolar and Basal Bone

    Alotaibi, Fawwaz; Alotaibi, Fawwaz; Department of Oral Biology (5/1/2015)
    The mandible is composed to two bone types: alveolar and basal. Previous studies on the mandible have shown that the alveolar bone resorbs more than the basal bone after tooth extraction or as a result of tooth movement. Reasons for why the resorption rates are different is not well understood. This research begins exploring the differences of the alveolar and basal bone by using comparison characteristics such as bone mineral density (BMD), gene expression, protein profiles, and number of osteocytes. The research investigates these characteristics by using Real time RCR to study the differences in gene expression and protein profiles of the alveolar and basal bone. Micro-CT was used in comparing density and bone architecture characteristics of the alveolar and basal bone. Immunohistochemistry was used to better understand how osteocytes are different between the two bone types in hopes of later being able to understand the differences in resorption rates. The real time PCR showed that four genes are expressed significantly higher in basal bone than alveolar bone: SOST, E-11, DMP-1, MEPE. Three of which are associated with mature osteocytes indicating that basal bone has more mature osteocyte phenotypes. Micro-CT data indicated that the basal bone is denser and less porous than alveolar bone. There was no significant difference in immunohistochemistry and further quantitative testing is needed to draw and significant correlation.

View more