Disabled-2 (Dab2) is a mitogen-responsive adaptor protein playing a key role in multifaceted cellular functions, such as endocytosis, epithelial-mesenchymal transition (EMT), immune function, stem cell differentiation, oncogenesis, cell signaling, and inflammatory responses. The adenosine deaminase RNA-specific binding protein (ADAR1) is a multifunctional RNA-editing enzyme that can convert adenosine to inosine, which can modulate gene expression and cellular functions in multiple pathways, such as mRNA translation by changing codons and the subsequent protein sequence, pre-mRNA splicing by changing splice site sequences, RNA stability by altering sequence for nuclease recognition, and RNA structure-dependent functions by altering RNA-protein interactions. ADAR1 has displayed a largely pro-tumorigenesis role, especially its immunosuppressive function in cancer cells, which attributes ADAR1 as a potential novel immune checkpoint for cancer treatment. In our lab, we employed an F9 mouse teratocarcinoma stem cell differentiating model and confirmed that Dab2 is an indispensable element for retinoic acid (RA)-induced F9 cell differentiation. Interestingly, our new findings indicated that during the process of RA-induced F9 cell differentiation, both the protein levels of Dab2 and ADAR1 are significantly upregulated, and siRNA-mediated Dab2 silence results in the silence of ADAR1. In addition, results from EMT models and statistical analysis from the human TCGA database further indicated that there is a positive correlation between the expression of Dab2 and ADAR1. Our results imply that Dab2 and ADAR1 may cooperate with each other to modulate cellular functions, which will present a novel mechanism for the mechanistic study of Dab2 in tumorigenesis.

ASSOCIATION OF AGE, GENDER AND RACE IN CHRONIC KIDNEY DISEASE PATIENTS WITH AND WITHOUT DIALYSIS 1Busayo Adeyemi Onatolu, 2Hemang Panchal, 3Edward Francis Leinaar, 1*Shimin Zheng, 2Timir K. Paul 1Department of Biostatistics and Epidemiology, College of Public Health, ETSU, Johnson City, TN 37614 2Department of Internal Medicine, Quillen College of Medicine, ETSU, Johnson City, TN, 37614 3Department of Health Services Management and Policy, CPH, ETSU, Johnson City, TN 37614 *Sponsoring faculty Introduction: Studies have shown that chronic kidney disease (CKD) is common among adults in the United States. The Centers for Disease Control and Prevention (CDC) states that 30 million people, or 15% of US adults, are estimated to have CKD. Forty-eight percent of those with severely reduced kidney function are not aware of having CKD, and therefore do not receive hemodialysis (HD). Methods: A nationwide inpatient sample database from 2012-2014 was used to identify all patients admitted to the hospital using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes (n= 534,845). Patients with dialysis dependent CKD (n=8,100) and CKD without dialysis (n=51,285) were compared to non-CKD patients (n=475,460). Hierarchical logistic regression was performed and p Results: Of the 534,845 patients, 88.9% were without CKD and 9.59% had CKD without HD and 1.51% had CKD with HD. Among patients with CKD, 13.64% were on HD and 86.34% were non-HD patients. The result shows that a higher proportion of patients with CKD without HD in the ≥ 80 years age group (≥ 80 = 37.84%, 65-79 = 36.94%, 50-64 = 20.80%, 35-49 = 4.12% and 18-34 = 0.30%) and a higher proportion of patients with CKD with HD in the 65-79 years age (≥ 80 = 16.30%, 65-79 = 41.79%, 50-64 = 33.09%, 35-64 = 8.09% and 18-34 = 1.29%). The OR of age group 18-34 compared to ≥ 80 is 5.690, 95% CI: 4.202,7.705, OR 35-49 is 4.552, 95% CI: 4.552, 95% CI: 4.103, 5.050, OR of 50-64 is 3.693, 95% CI: 3.444, 3.961 and OR 65-79 is 2.626, 95% CI: 2.457, 2.807. Males had higher rates of CKD than females, without HD (Male= 63.12%, female= 36.88%, p Conclusion: From this study, males had higher rates of CKD with and without HD than females, the age group ≥ 80 years had higher proportion of CKD without HD and those between 65-79 years had higher number of CKD with HD. Whites had higher rates of CKD with and without HD than other races.

End of life planning is an essential component of complete care for patients established in a primary care clinic. Family medicine clinics, where treatment begins with birth and ends with death, it is imperative for clinicians both seasoned and new have the knowledge and resources available to ensure effective discussion of this complex subject. Surveys across the country of both patients and providers show that anywhere between 5-25% of patients have an advanced directive filled out and on file. Furthermore, most patients report a preference for holding this discussion with their established primary care physician. Numerous barriers have been identified in previous surveys and studies that tend to limit this discussion in the primary care setting in the academic and private sector. By identifying these barriers and providing possible solutions, primary care providers should be able to more effectively facilitate and navigate a discussion about end of life care. We designed a quality improvement project for family medicine residents in an effort to identify location specific barriers and to provide an educational didactic session which is aimed at overcoming these barriers. A survey was designed to be filled out by participates prior to the presentation to measure baseline comfort and understanding of advanced directives. The same survey was administered after the presentation to measure the effectiveness of the presented didactic. Statistical analysis of these two surveys will be completed and reviewed. The expected outcome is that participants in the session leave with an improved comfort with the subject of advanced directives and end of life planning. Participants are expected to have increased knowledge of available resources that can be utilized during these discussions. By providing this session to both residents and supervising physicians, the hope is that an increase in documented advanced care directives will be seen at the family medicine clinic. If this session is found to be an effective tool to address the identified barriers to end of life planning, it may be suitable to extend throughout the family medicine department at East Tennessee State University. Following this didactic session, multiple residents reported utilizing resources that were presented during discussions, with patients in regards to end of life planning and advanced care directives.

INTRODUCTION: Adults with hearing loss who report difficulty understanding speech with and without hearing aids often also report increased mental or listening effort. Although speech recognition measures are well known and have been in use for decades, measures of listening effort are relatively new and include objective measures such as working memory tasks, pupillometry, heart rate, skin conductance, and brain imaging. OBJECTIVES: The purpose of this study is to evaluate an electroencephalogram (EEG)-based method to assess cognitive states during a speech in noise perception task. METHODS: High frequency alpha (11-13 Hz), low frequency alpha (8-10 Hz), and theta (4-7 Hz) frequencies were assessed with EEG during the Words-In-Noise test that utilizes seven different signal-to-noise ratios (SNR). Changes in high frequency alpha have been associated with cognitive demands and low frequency alpha has been associated with cognitive inhibition. Changes in theta have been associated with encoding information and increased listening effort. RESULTS: Results from the current study indicate a strong negative correlation between self-reported listening effort and speech in noise word recognition performance. Low frequency alpha power results suggest a power curve reflecting a point of maximum cognitive inhibition as a function of SNR. Results for high frequency alpha power show possible increased cognitive demand in lower SNR. Theta frequency shows no effect of SNR. DISCUSSION: Low frequency alpha results show a possible role of cognitive inhibition in words-in-noise speech recognition. High frequency alpha results show that lower signal-to-noise ratio conditions could increase cognitive demand. The EEG methodology used to measure theta may not be optimal to capture signal-to-noise changes. Understanding the neurological underpinnings of these frequencies could assist in the future development of an objective clinical tool to measure listening effort in patients with and without hearing loss.

Vitamin D3 (cholecalciferol) (Vit D3) is a form of vitamin D (Vit D) that is essential for normal body function in humans. Vit D is a fat-soluble vitamin used to prevent osteoporosis in adults, prevent rickets in children, and supplement Vit D deficiencies which are seen worldwide. Physicians usually recommend 2,000 International Units (IU) Vit D3 for these deficiencies, but due to the poor aqueous solubility of Vit D3, this dose can be insufficient for patients. It would be more beneficial to recommend 5,000 IU. In 1994, the Dietary Supplement Health and Education Act was passed defining vitamins as “dietary supplements” and no longer required FDA registration prior to marketing. Dissolution results are expressed as the percent of the content released into solution, with a target of 85 to 125%. There is not an effective dissolution test existing for Vit D3 product evaluation, so an optimized dissolution test for Vit D3 was developed and used to evaluate non-prescription Vit D3 products. The current FDA guideline for Vit D3 dissolution is USP Apparatus II with 500 mL of 0.3% sodium dodecyl sulfate (SDS) in water. Since Vit D3 is not very water soluble, a surfactant is required for it to go into solution. The research was started with a larger volume (1 L) and with commonly used pharmaceutical grade surfactants: Triton X-100, Tween 80, Span 20, and sodium lauryl sulfate (SLS). SDS was eliminated due to interference with the HPLC analysis. Using two Vit D3 test products, which previous research found to have consistent drug content, each of these surfactants were tested at 0.8%. After evaluating the HPLC results, Triton and Tween were eliminated due to too much interference with the analysis process. The interference consisted of a large initial solvent front peak, elevated baseline, overlap with the drug peak, and required significant decrease in the mobile phase flow rate. Changing the mobile phase to 50/50 methanol/1-propanol solved the flow rate issue and peak separation overlap, but not the large solvent peak or elevated baseline. Dissolution testing continued using SLS and Span using 0.6%. Dissolution of the two test products, designated A and B, with 2 representing 2000 IU and 5 being 5000 IU, yielded higher values using SLS (A2 75.5%; A5 152.8%; B2 30.9%; B5 36.6%) compared to Span (A2 15%; A5 136%; B2 20.3%; B5 63%). Additional work continued to determine the best concentration of SLS. Better dissolution results were obtained using 1.2% (A2 88.1%; A5 156.7%) when compared to 0.3% (A2 87.4%; A5 153.2%), 0.6% (A2 70.7%; A5 132.2%), and 0.9% (A2 79.7%; A5 150.5%). Use of 1.5% did not yield a significant improvement (A2 84% vs 86.8%; A5 146.4% vs 144.6%), so 1.2% was chosen as this would minimize the amount of surfactant in the samples. The final dissolution method was created using a USP Apparatus II in 1000 mL containing 1.2% SLS in water. Based upon these characteristics, SLS 1.2% gave a good balance of minimizing surfactant concentration and analytical interference while maximizing Vit D3 dissolution.

TITLE: Racial disparities associated with colon cancer screening in a nationally representative sample; A cross-sectional study AUTHOR INFO Yorandos Tafesse MD1 Manik Ahuja PhD, MA1 Author Affiliations: 1College of Public Health, East Tennessee State University, Johnson City, TN 37614, United States Colon cancer impacts nearly 2 million individuals in the U.S. each year. Early detection of colon cancer using colonoscopy can reduce the risk of mortality. The United States Preventive Services Task Force (USPSTF) recommends routine screening for colon cancer for all adults 50 to 75 years of age. Colon cancer screening behavior is different across a variety of predictor variables. Previous studies have identified older age, male gender, higher education, higher income, marriage, and the presence of chronic diseases to be associated with increased odds of colon cancer screening. However, less is known about the role of racial differences in screening. This study aims to determine if colon cancer screening rates are different between Whites and racial minorities in the United States controlling for potential confounders. This research can help bridge the existing gap on this topic and aid in identifying high-risk racial groups that could be targeted by future intervention strategies. We used cross-sectional data from the 2019 Behavioral Risk Factor Surveillance System, a nationally representative U.S. telephone-based survey of adults aged 18 years or older. We extracted data for adults age 50 or older (n=10,972). Logistic regression analyses were conducted to test the association between race and colon cancer screening. We also included chronic disease status, alcohol use, smoking, gender, and age in our model. Chronic disease status was coded as self-report 2 or more, 1 and 0 chronic diseases (referent), which included the summation of heart disease, hypertension, COPD, and diabetes. Overall, colon cancer screening is as follows among Whites (77.2%), Blacks (72.4%), Asian (60.1%), American Indian/Alaska Native (69.7%), and Hispanic (68.6%). Logistic regression results revealed that having 2 or more chronic diseases (OR=1.73; 95% CI 1.53,1.96), 1 chronic disease (OR=1.45; 95% CI 1.31,1.65), and female gender (OR=1.14; 95% CI 1.04,1.23) were associated with higher odds of screening. Race/ethnic minority status (OR=0.72; 95% CI 0.65, 0.81), low income (OR=0.64; 95% CI 0.57,0.70), and less than high school education (OR=0.71; 95% CI 0.59,0.84) were associated with lower odds of screening. Our research showed that racial minorities have lower odds of colon cancer screening after adjusting for gender, age, chronic diseases, income, and education status. Preventive practices should focus on increasing awareness on and availability of colon cancer screening means to racial minorities in the United States. Further research on the association between race and other screening modalities will help maximize the impacts of targeted interventions.

Post-traumatic stress disorder (PTSD) is characterized by fear extinction deficit; chronic stress worsens this deficit. Using a Chronic Unpredictable Stress (CUS) model, we previously found that CUS increased fear extinction deficit in female mice and knockout of Ciliary Neurotrophic Factor (CNTF) attenuated it. The amygdala, specifically the medial amygdala, is strongly associated with fear conditioning and extinction. CUS increased CNTF and reduced Urocortin 3 (UCN3) in the medial amygdala, suggesting CNTF-mediated UCN3 inhibition may be involved in CUS-induced deficit of fear extinction. The medial amygdala connects to the hypothalamic paraventricular nucleus (PVN) via posterior bed nucleus of stria terminalis (pBNST) and mediates the stress response (Fig. 1). The objective of this project is to determine whether CUS affects CNTF, UCN3, and CNTF-related cytokine leukemia inhibitory factor (LIF) and interleukin-6 (IL-6) in the pBNST and hypothalamic PVN. Hippocampal CNTF expression was also examined as a brain region outside of the medial amygdala-pBNST-hypothalamic PVN circuitry. 4 groups (5 mice/group) of CNTF+/+ and CNTF-/- mice were treated with 4 weeks of CUS or control handling. At the end, fresh brain samples were collected. The hypothalamic PVN, pBNST and hippocampus were punched out from 600-700 um cryostat frozen sections. CUS was applied for 4 weeks. The control mice were handled daily for 4 weeks. RNA was extracted from tissue using QIANGEN Rneasy mini kit. BCA assay was performed to analyze protein concentration, then 10% SDS gel was used to run the protein samples. Statistical analysis included one-way ANOVA followed by Bonferroni multiple comparison or 2-tailed T test. p <0.05 was defined as significant difference. In the pBNST, CUS did not affect CNTF and UCN3 mRNA expression. However, UCN3 protein was upregulated by CUS in CNTF+/+ but not CNTF-/- mice, suggesting CNTF inhibits UCN3 expression, possibly through post-transcriptional mechanism. CUS did not alter LIF and IL-3 in the pBNST. CUS did not alter CNTF mRNA expression in the PVN and further study will measure UCN3 mRNA and protein in the PVN. Finally, there was no CUS effect on CNTF, LIF and IL-6 mRNA in the hippocampus. These results and further studies are useful in development of therapeutic medications and drug targets in the case of chronic stress.

Cerebrovascular accidents (CVAs) are a leading cause of morbidity and mortality in the United States. Metabolic derangements such as hypoglycemia, infections, brain masses or lesions, neurodegenerative disorders, neuropathies, myelopathies, seizures, syncope, types of migraines, and many other disorders may mimic CVA. Our case presents a 38-year-old female who was evaluated in the emergency department with a three- hour history of headache, lethargy, left- sided upper extremity weakness, facial droop, and dysarthria. A CVA workup was initiated and she immediately underwent a computed tomography (CT) scan of the head which revealed no intracranial hemorrhage. She was unable to provide a thorough medical history due to lethargy, however she was able to answer yes/no questions to screen for tissue plasminogen activator (tPA) qualification. She qualified based on her screening results and was administered tPA for her presumed ischemic CVA. She was then monitored in the intensive care unit for twenty-four hours. Due to reoccurrence of headache and left-sided weakness, as well as recent administration of tPA increasing risk of hemorrhage, she underwent two subsequent negative non- contrast head CT scans to rule out bleeding during that time. On hospital day two, magnetic resonance imaging (MRI) of the head, neck, and spine were performed which were also negative for infarct or hemorrhage. A more detailed history from our patient revealed previous migraine headaches, but her left sided weakness and dysarthria were new symptoms. With this information, it was suspected that she was suffering from a hemiplegic migraine, a rare mimic of CVA. Prochlorperazine, diphenhydramine, valproic acid, and corticosteroids were administered for migraine treatment, which aborted her symptoms entirely. Topiramate was then started for migraine prophylaxis. Daily low-dose aspirin was also initiated due to inability to fully rule out CVA/transient ischemic attack (TIA). An outpatient neurology follow up was scheduled on discharge. In clinical practice, hemiplegic migraines and CVA/TIA may be difficult to differentiate as symptoms often overlap. A detailed history and physical exam with careful attention to associated symptoms and timing of symptom onset is essential to formulating a correct diagnosis. This must be done quickly, as tPA is a high-risk medication with a narrow time window for administration. In conclusion, not all disease processes have an available “gold standard” diagnostic test to differentiate similar diagnoses. MRI of the brain is usually performed to differentiate ischemic CVA from TIA; however, imaging is not useful to differentiate hemiplegic migraine from TIA. Therefore, performing a thorough history, physical exam, and chart review is paramount to provide patients with the correct treatment as well as prevent adverse outcomes. It is the responsibility of the clinician to make difficult decisions weighing the risks and benefits of providing various treatments or interventions, and to know the complications of those treatments. Disease processes mimicking CVA must be considered in all patients, as treating an incorrect diagnosis can have devastating effects.

As NASA and other space programs around the world prepare to send astronauts into space for longer missions, it is becoming imperative to understand the biological effects of spaceflight on the human body. In order to better understand how the long-term spaceflight environment affects humans biologically, researchers often utilize other model organisms, like mice, whose biological systems are comparable to human body systems. Our study was performed to determine if spaceflight had any effect on the thickness of the muscular layers of the uterine tissue of female mice. In other words, how does the thickness of the muscular layers in the uterus of spaceflight mice compare to that of control mice that were not subjected to spaceflight. For this study mice were divided into 4 groups (flight animals, baseline animals, vivarium controls, and ground controls) and the flight mice subjected to 37 days of spaceflight. Upon tissue retrieval and histological preparation, five random measurements of the outer longitudinal muscular layer and five random measurements from the inner circular muscular layer of each tissue sample were made. The average thickness for each layer was then calculated and statistical analysis used to determine differences between the four groups of mice. At the time of this presentation final measurements and statistics had not been completed.

Transgender individuals are defined as those whose gender does not match the sex they were assigned at birth. Healthcare providers receive inadequate training in transgender medicine, which could lead to provider stigma and lower health outcomes and higher health disparities. The purpose of our study was to assess the effect of an educational intervention on first and second year ETSU medical students’ knowledge and attitudes regarding transgender healthcare. A transgender healthcare-centered Integrated Grand Rounds (IGR) was used as a setting to conduct a 9-item survey regarding definitions, medical management, and attitudes/comfort levels with transgender care. First and second year medical students (n=140) who participated in the intervention had the option to complete pre and post surveys on paper before and after IGR. Of the 140 participants, 138 (98.6%) completed the pretest and posttest measures. The participants’ attitudes about transgender patients and their comfort in treating transgender patients significantly improved between pre and posttest surveys (p