2019

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Safety and Efficacy Analysis of Balloon Cryoablation vs Radiofrequency Ablation in Atrial Fibrillation: A Retrospective Analysis. (SECARA AFib TRIAL)
(2019-03-05) Khan, Ahsan; Gupta, Karan; Wilson, Kimberly; Jipescu, Daniel; Subramanian, Anand; Thambidorai, Senthil; Johnson, Douglas; Timins, Aaron; Patel, Aman
Background: According to the ACC/AHA/HRS guidelines, Pulmonary-Vein Isolation has become the cornerstone approach in ablation for patients with medication refractory paroxysmal atrial fibrillation. (Class 1). Radiofrequency ablation is the most frequently employed technology followed by balloon cryoablation. According to multiple, smaller studies in recent past, both procedures have similar efficacy in terms of recurrence with little difference in complication rate. The FreezeAF trial, a 5-year observational study from 2011-2016 involving 4,073 patients, showed a better safety profile with radiofrequency ablation with lower rates of phrenic-nerve injuries in comparison to those of balloon cryoablation. However, some studies have shown that the rate of perforation was higher with thermal ablation. The landmark FIRE AND ICE Trial, a multicenter randomized controlled noninferiority trial of almost 800 patients published in 2016 in NEJM by Karl Heinz et al. showed a similar result in terms of efficacy and end safety result between the two. A systematic review of 7200 patients by Yi-He Chen et al. concluded that cryoablation has fewer rates of atrial fibrillation recurrence, shorter procedural duration and similar fluoroscopy times. Similar other studies are favoring the use of balloon cryoablation due to lower rate of hospitalizations, repeat ablation, and cardioversions. Methods: Retrospective single center chart review. Results: Cryoablation ( n -139 ) vs RF ( n -507) MACE - ( OR 2.62, p: 0.045, CI: 1.1 - 6.28) Non cardiac ADEs (OR 6.47, p: 0.0029, CI 2.3098 - 18.1395) Death: ( 1 vs 2, OR 1.84, p: 0.52, CI: 0.16-20.28) Efficacy: Persistent afib at discharge: ( OR 1.69, p: 0.08, CI: 0.85-3.07 ) Mean Contrast volume: (78 cc vs 4.48 cc, p Mean LA volume: (3.94 vs 4.59) Mean Fluoroscopy time: ( 31 vs 32 mins, p: 0.86) Conclusion: In our retrospective single-center study, patients who underwent cryoablation for pAF had a statistically significant higher incidence of MACE and noncardiac ADEs. There was no significant difference in mortality rates or primary efficacy.
Surface PCNA enables pancreatic and colon cancer stem cells to inhibit NK cell effector function
(2019-03-05) Mathew, Porunelloor A.; Malaer, Joseph
Purpose: Cancer stem cells (CSC) are a subset of tumor cells that have a stem-cell-like phenotype and are thought to facilitate metastasis by evading peripheral NK cell effector function. NK cell function is regulated by the balance of activating and inhibitory receptors binding to ligands on the surface of target cells. Cancer cells may escape NK cell killing by expressing or secreting ligands for NK cell inhibitory receptors. NKp44, a member of the natural cytotoxicity receptor family, can function as either an activating or an inhibitory receptor depending on ligand interaction. Proliferating cell nuclear antigen (PCNA) associates with MHC class I and forms an inhibitory ligand for NKp44, resulting in the inhibition of NK cytotoxicity. We hypothesize cell surface PCNA can be used as a marker for CSC and as a potential immunotherapeutic target for pancreatic and colon cancer. Methods: Pancreatic (Panc-1) and colon (HCT 116) cancer cell lines were labeled with antibodies against PCNA, CD44, and CD133 and flow cytometry was performed to determine surface expression. CSC were identified as being CD44+CD133+. Cells were labeled and sorted via FACS; CSC transcription factors NANOG, SOX2, and Oct-4 were analyzed by qRT-PCR from sorted populations. NK receptor-ligand interactions were blocked by incubating cells with anti-PCNA, anti-NKp44, or control antibodies; interferon gamma and chromium release assays were performed. Results: In both Panc-1 and HCT 116 cells, a PCNA+CD44+CD133+ population was detected and enriched in naturally detached cells. Furthermore, cell sorting and qRT-PCR determined cells with cell surface PCNA have increased expression of CSC transcription factors compared to cells lacking surface PCNA. Blocking the PCNA-NKp44 interaction enhanced the specific lysis of target cells by NK cells and altered the release of interferon gamma. Conclusions: Cell surface PCNA is associated with co-expression of CD44 and CD133 as well as increased CSC transcription factor expression. Additionally, cell surface PCNA alters interferon gamma secretion and facilitates escape from NK cell killing. Our data suggest that blocking NKp44-PCNA interactions may provide a novel immunotherapeutic target for pancreatic and colon cancer stem cells and prevent metastasis.
The Link Between Low Back Pain And Diabetes: Gene-Based Association Study In People With Comorbid Diabetes Mellitus And Low Back Pain
(2019-03-05) Pathak, Gita; Phillips, Nicole R.; Licciardone, John C.; Schmitt, Monika
Purpose Diabetes mellitus type 2 is a disease associated with chronic pain. Mechanisms of this association are not fully understood. Few studies have explored the genetics of this association, and an independent genetic link between diabetes and low back pain (LBP) has not been completely investigated. We hypothesize that variants in candidate genes are associated with comorbid diabetes and LBP phenotypes. Methods This cross-sectional study is a part of a larger study of subacute and chronic LBP within the PRECISION Pain Research Registry. Subjects were recruited from the Dallas–Fort Worth Metroplex and reported LBP for at least 2 months (subacute) or 6 months (chronic) for half or more of the days with the relevant time period. Primary outcomes were assessed using a Numerical Rating Scale (NRS) for pain intensity, the Roland-Morris Disability Questionnaire for back-specific functioning, and the Patient-Reported Outcomes Measurement Information System (PROMIS) for quality of life measures. Study participants self-reported diabetes. Biological samples were collected to determine participants’ genotypes using the Infinium Global Screening Array. Analyses were conducted using SPSS among 488 study participants, 109 of whom reported diabetes. Twenty-seven candidate genes concurrently implicated in both pain phenotypes and diabetic phenotypes were identified from the literature. These candidate genes were used to perform a gene-based association study (GBAS) to identify their potential association with diabetes and LBP. Genetic variants were mapped to candidate genes for association with each of the pain phenotypes after adjusting for age, sex, diabetes status, and ancestry components 1-10 using MAGMA. Results GBAS results point to variants in the PRKCA gene as being associated with both NRS of LBP intensity and diabetes. PRKCA is a family of protein kinases implicated in neuropathic pain and formation of advanced glycation end products. Conclusions Of the 27 genes tested, only variants in PRKCA are significantly associated with LBP and diabetes in the PRECISION cohort. These findings build on a framework which suggests that genetic predisposition in PRKCA may underlie diabetes and LBP.
A Bigger View: US public TB prevention initiatives with a broader health systems perspective
(2019-03-05) Miller, Thaddeus; Grebennikov, Sarah; Stockbridge, Erica L.; Hussain, Anusha
Background: Tuberculosis (TB) is a complex disease and persists as a greater threat than most understand. Responsibility for TB treatment and control has generally fallen to public health agencies. Unfortunately, important limitations to the public health sector’s of TB control are beginning to show. UNTHSC recently hosted a “systems thinking symposium” with the goal of helping public health authorities view their work in broader context. This project presents an analysis of industry perspectives on public TB control initiatives drawn from symposium discussions. Purpose: We analyzed 36 hours of discussions to better understand how CDC’s messaging around TB prevention and managing latent TB infection (LTBI) in particular is heard, accepted, and potentially acted on in various health care sectors. Methods: Approximately 30 participants from across the US healthcare system discussed how incentives and disincentives within their industry might affect TB-related public health initiatives. Discussion sessions focused on how at-risk patients self-identify and seek care; how providers identify potentially at-risk patients; how clinical evaluation is initiated and conducted; treatment initiation; and treatment completion. We analyzed discussion transcripts to identify industry perspectives, opportunities and barriers, and potential gaps in TB control initiatives. The unit of study was the program or industry represented by responses, not individual respondents, and the North Texas Regional IRB determined the project not to be human subjects research. Results: We identified the 15 most commonly used context appropriate words from a 78,604 word transcript. These were mapped to broad themes such as improving screening target populations, continuity of care, and potential roles of the non-public health sector. Notable barriers were identified within the clinical and managed care sectors, including consistent questioning of TB prevention as a priority activity, including potential risks, benefits, and the value proposition. Conclusions: CDC’s promotion of targeted LTBI screening and treatment, and TB prevention in general, is not well reflected in the attitudes of the non-public healthcare sector in our sample. Most health care professionals would choose not to prioritize LTBI due to the logistics of insurance and more urgent and emergent diseases. It may be important for CDC to consider who and how they target TB elimination messaging in order to enhance impact.
Influence of ovarian hormone deprivation length on the neuroprotective effects of genistein in stroke
(2019-03-05) Metzger, Daniel; Sun, Fen; Sumien, Nathalie; Schreihofer, Derek; Oppong-Gyebi, Anthony
PURPOSE: Advancing age increases women’s susceptibility to stroke compared to men, especially after the menopausal transition. Among the reasons proposed for high stroke incidence in postmenopausal women is a significant decrease in estrogen (E2) concentration, based on well-established evidence that E2 is neuroprotective during ischemia in animal studies. While E2 treatment can be beneficial, extended delays in its replacement can result in detrimental actions on the brain which contributes to widespread mistrust of menopausal hormone therapy. Interest in the beneficial effects of soy isoflavones has grown as a viable alternative for E2. However, results from clinical trials have been inconsistent as there seems to be no consensus on the benefits of soy isoflavones in menopausal women. Notwithstanding, evidence suggests a time-dependent benefit of soy isoflavones, even though there is no systematic assessment in preclinical studies to identify the window of opportunity for their proposed optimal benefits. Hypothesis: After long-term hormone deprivation, the soy isoflavone genistein will maintain the ability to provide neuroprotection in the brain following aging and the loss of endogenous E2 in an experimental stroke model. METHODS: Young adult and retired proven breeder Sprague-Dawley rats ( [greater than] 9 mo) were bilaterally ovariectomized, divided into 2 post-ovariectomized time points (2 and 12 weeks) and fed with an isoflavone free (IF) diet. At the end of each time point, rats were continued on IF diet or switched to genistein diet. Two weeks later, rats underwent transient middle cerebral artery occlusion for 60 mins. After stroke rats were subjected to a series of behavioral tests including neurological function, cylinder test, rotarod, and the Morris Water Maze (MWM). RESULTS:Our results demonstrated a significant effect (p CONCLUSION: Dietary genistein had little effect on the sensorimotor outcomes but holds a promise in improving cognitive function post-stroke in the long term.
The Endothelin Receptor Antagonist Macitentan Ameliorates Endothelin-Mediated Vasoconstriction and Promotes Neuroprotection of Retinal Ganglion Cells in Rats.
(2019-03-05) Krishnamoorthy, Vignesh; wei, Zhang; Kodati, Bindu; Chavala, Sai; Krishnamoorthy, Raghu; Stankowska, Dorota; Harris, Payton
The Endothelin Receptor Antagonist Macitentan Ameliorates Endothelin-Mediated Vasoconstriction and Promotes Neuroprotection of Retinal Ganglion Cells in Rats. Payton Harris Vignesh Krishnamoorthy Wei Zhang Bindu Kodati Sai Chavala Raghu Krishnamoorthy Dorota L. Stankowska 1. Texas College of Osteopathic Medicine, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth TX 76107 2. Department of Pharmacology and Neuroscience, North Texas Eye Research Institute, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth TX 76107 Purpose: To determine if dietary administration of the dual ETA/ETB receptor antagonist, macitentan, could protect retinal ganglion cells (RGCs) following endothelin-1 mediated vasoconstriction in Brown Norway rats. Methods: Adult male and female Brown Norway rats were either untreated or treated with macitentan (5 mg/kg body weight) once a day for 3 days followed by intravitreal injection of either 4 µl of 500 mM ET-1 or vehicle in one eye. Imaging of the retinal vasculature using fluorescein angiography was carried out a various time points including 2, 5, 10 and 20 minutes. Following the imaging of the vasculature, treatment of rats was continued for 1 week with either macitentan (5 mg/kg/body weight) in dietary gels or untreated control gels. After euthanizing the rats, retinal flat mounts from the rats were prepared, immunostained for RGC marker Brn3a, imaged and surviving RGCs were counted in a masked manner. Results: Vasoconstrictive effects following intravitreal ET-1 injection were greatly reduced in rats administered with macitentan in the diet prior to the ET-1 administration. ET-1 intravitreal injection produced a 45% loss of RGCs which was significantly reduced in macitentan-treated rats and RGC counts were similar to that observed in control retinas. Conclusions: The endothelin receptor antagonist, macitentan, has neuroprotective effects in retinas of Brown Norway rats that occurs through different mechanisms, including, enhancement of RGC survival and reduction ET-1 mediated vasoconstriction preventing ischemia.
Risk Factors Associated with Stroke in Pediatric Patients Undergoing Fontan Palliation
(2019-03-05) Duncan, Jay; Hamby, Tyler; Javed, Mahnoor
Risk Factors Associated with Stroke in Pediatric Patients Undergoing Fontan Palliation Puprose: Congenital heart disease is the leading known cause for stroke in childhood. The Fontan operation is performed as the third palliative procedure in patients who have complex single ventricle physiology. Patients undergoing Fontan Palliation are at risk for 3 types of strokes: watershed, embolic, or hemorrhagic. Stroke following Fontan Palliation can result in significant deterioration of functional ability. The incidence of this complication seemed higher at Cook Children’s Medical Center (CCMC) as compared to a previous study done at Children’s Hospital in Boston (2.6%). Therefore, the aim of our study is to identify variables contributing to the development of stroke and the risk factors associated with it. The hypothesis is that there are identifiable and potentially modifiable intra-operative and post-operative risk factors that are present in Fontan patients who have radiographic and clinical evidence of stroke. Methods: This was a retrospective chart review of 149 pediatric patients who underwent Fontan Palliation at CCMC between 2007 and 2017. Exclusion factors were any patient undergoing revision of prior Fontan or death within 72 hours of the operation. Covariates included AV valve regurgitation, ventricular function, SVC pressure (pre and post op), and intraoperative change in hematocrit. A Fisher’s exact test was used and p Results: Overall 11% post-Fontan patients had a stroke, all of which were watershed infarcts. Stroke was statistically significantly associated with pre- and post-operative AV valve regurgitation, and depressed ventricular function. Cardiac bypass time, mean arterial pressure, SVC pressure (pre- and post-operative) and intraoperative changes in hematocrit were not significantly associated with stroke. Though the relationship wasn’t significant, all stroke patients had a vasoactive infusion score greater than 5. Conclusion: Pre-Fontan physiology is the single most important factor when determining the risk of developing a watershed infarct with Fontan procedure. AV valve regurgitation and depressed pre-operative single ventricular function are potentially the most significant risk factors for perioperative stroke. This information may be helpful in counseling families about potential post-operative complications.
Activation of TRPV4 channels reduces IOP and improves outflow facility by regulating eNOS dependent nitric oxide release from the trabecular meshwork
(2019-03-05) Kasetti, Ramesh; Maddineni, Prabhavathi; Millar, J. Cameron; Zode, Gulab; Patel, Pinkal
Purpose: Nitric oxide (NO) is known to reduce intraocular pressure (IOP) by relaxation of the trabecular meshwork (TM) and distal vessels of the conventional outflow pathway. However, the intrinsic mechanisms by which outflow pathway tissues regulate NO production is yet to be elucidated. In vascular endothelium, activation of mechanosensory transient receptor potential vanilloid 4 (TRPV4) channels results in endothelial nitic oxide synthase (eNOS) mediated NO release, which in turn promotes vasodilation. Here, we determined whether activation of TRPV4 regulates IOP and conventional outflow via NO release in the TM. Methods: In wildtype (WT) and glucocorticoid-induced ocular hypertensive (OHT) C57BL/6J mice, the effect of TRPV4 agonist GSK1016790A on IOP and outflow facility was determined using rebound tonometry and constant-flow infusion method respectively. Effect of TRPV4 agonist on eNOS activation and NO production was determined using Western blot and fluorometric DAF-FM assay in primary human TM cells and ex vivo cultured human TM donor tissues. We report for the first time a method for electrochemical measurement of NO in human anterior segment donor tissues using NO microsensors. Results: Topical administration of TRPV4 agonist GSK1016790A significantly reduced IOP (Pin WT and OHT mice compared to contralateral control eyes. In OHT mice, treatment with GSK1016790A resulted in increased outflow facility (P=0.02)compared to contralateral vehicle treated eyes. We further demonstrate that TRPV4 activation by GSK1016790A resulted in increased eNOS phosphorylation in GTM3 cells, primary human TM cells, and cultured human TM donor tissues. Activation of TRPV4 in primary TM cells and ex vivocultured human TM donor tissues resulted in increased DAF-FM fluorescence, which signifies increase in TRPV4-mediated NO production. Treatment of human anterior segments with TRPV4 agonist resulted in increased production of NO as detected electrochemically using NO microsensors. Nonselective inhibition of NOS by L-NAME abrogated the IOP lowering effect of TRPV4 agonist in mice and reduced TRPV4-mediated NO production in outflow pathway cells and donor tissues. Conclusion: TRPV4 activation improves IOP and outflow facility, perhaps by regulation of eNOS dependent NO release.
Radiation-mediated effect on exosomal and non-exosomal-derived microRNA-21 (miR21) gene expression by Triple Negative Breast Cancer cell line MDA-MB-231
(2019-03-05) Chaudhary, Pankaj; Jones, Harlan; Choe, Jamie Y.
Background: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype which lacks estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor-2 receptor (HER2). TNBC is therefore not responsive to hormonal treatment and currently lacks targeted therapies. Overexpression of miR21 is routinely observed with TNBC and correlates with advanced tumor stage and lymph node metastasis. MDA-MB-231 is a metastatic human TNBC cell line with high recurrence rate via metastasis to secondary sites. Specialized extracellular vesicles called exosomes are involved in intercellular communication and have been postulated to have roles in tumor metastasis. Objective: In this study, we evaluate the effect of high-dose radiation on viability of MDA-MB-231 and identify changes in miR21 expression in cells and exosomes released in response to ionizing radiation. Methods: MDA-MB-231 cells (obtained from American Type Culture Collection) were cultured and irradiated with single dose exposure to 8.6 Gy (low dose) and 17.2 Gy (high dose). At 24h post-irradiation, cells were assessed for viability, proliferation, and wound healing. Exosomes were isolated from culture medium at 48h post-irradiation using differential ultracentrifugation method and evaluated for size and purity. Western blot confirmed isolation of exosomes by determining expression of established exosome membrane protein markers CD81 and TSG101. RT-qPCR evaluated expression of miR21 in cells and exosomes. Results: High-dose (17.2 Gy) radiation suppressed MDA-MB-231 proliferation based on MTT and wound healing assays. MDA-MB-231 cells exposed to 8.6 Gy showed marked upregulation of cellular miR21 and relative downregulation of exosomal miR21; exposure to 17.2 Gy resulted in downregulation of both cellular and exosomal miR21 relative to the control. Conclusion: This pilot study demonstrated that tumor cells may display compartmental differential expression of miRNA in response to radiation and suggests that miRNA expression in cells may not be predictive of exosomal cargo.
Adolescent Health Data: Feelings of Depression and Marijuana Use
(2019-03-05) Thompson, Erika; Davis, Ambriale
Adolescent Health Data: Feelings of Depression and Marijuana Use Objective The purpose of this study is to examine an association between feelings of depression and marijuana use amongst high school students in the United States. Methods Data were analyzed based on the Youth Risk Behavior Surveillance System (YRBS), 2017. SAS 9.4 was used to apply survey weighting procedures to the bivariate and logistic regression models as well as to calculate univariate and bivariate descriptive statistics, and crude and adjusted odds ratios for the outcome, exposure, and covariates (n=13,916). Outcome was measured as “During the past 12 months, did you ever feel so sad or hopeless almost every day for two weeks or more in a row that you stopped doing some usual activities” and operationalized by yes/no. Exposure was measured by ““during your life, how many times have you used marijuana” and operationalized as no if zero and yes if any other number. Results Students who had feelings of depression were more likely to have ever used marijuana (49.1%) than those who did not have feelings of depression (29.4%). Also, females were more likely to have experienced feelings of depression when compared to males, 67.2% and 32.8% respectively. High school students who ever tried marijuana had 2.46(95% CI:2.15-2.82) times the odds of feeling depressed compared to those who had never tried marijuana. Female students had 2.73(95% CI:2.37-3.13) times the odds of feeling depressed compared to male students. Black or African American, 0.83(95% CI:0.69-0.99), and 15 year old, 0.78(95% CI:0.64-0.96), students had less odds than whites and those 17 years and older respectively. Conclusions This study revealed that students who had feelings of depression were more likely to have ever used marijuana compared to students that did not. Race and age were protective factors for depression. Female students had almost three times the odds of feeling depressed than males. Results can inform future research surrounding attitudes of marijuana use among high school students with feelings of depression in order to prevent or delay marijuana use in this population.
Constrictive Pericarditis: When Horses Become Zebras
(2019-03-05) TERHARK, MATTHEW
Background: Disease of the pericardium can be broken down into 3 pericardial compressive syndromes. Of particular interest involving the following case is that of constrictive pericarditis. This disease process is typically secondary to loss of the normal elasticity of the pericardial sac. Precipitating factors for loss of physiologic elasticity of the pericardial sac include idiopathic, viral, connective tissue disorders, iatrogenic neoplastic processes. Case information: A 57yo male presented to PCP with upper respiratory symptoms, treated with antibiotics, failed to follow up with PCP initially. Continued to experience worsening shortness of breath, was referred to pulmonology who identified significant right sided infiltrate on chest x-ray. Patient directed to our facility where chest tube was placed and TPA administered for loculated pleural effusion. Patient required pressor support following administration and echocardiogram was obtained revealing pericardial calcifications. Patient underwent left heart catheterization followed by staged pericardiectomy then right sided thoracotomy. Patient tolerated procedure well and underwent an uncomplicated postoperative course. Conclusions: While the symptoms of upper respiratory infection often lead to a benign outcome the potential for adverse disease sequelae is broad. In this particular case the patients likely viral URI likely lead to the subsequent diagnosis of constrictive pericarditis. In order to prevent permanent and likely progressive symptoms as seen with constrictive pericarditis the patient underwent a pericardectomy within a week of identification. The patient tolerated this procedure well and had complete resolution of constrictive pericarditis symptoms. In general, Patients experiencing constrictive pericarditis typically present with symptoms related to fluid overload (i.e.-edema, ascites) owing to a diminished cardiac output. As seen with this patient, treatment often involves pericardiectomy otherwise patients are often left with permanent and progressive symptoms.
Shoulder Balance Outcomes After Spinal Fusion
(2019-03-05) LaMont, Lauren; Section, Jarren
Purpose: The purpose of our study is to assess short and long term effects of posterior spinal fusion on shoulder balance and determine the correlation between osseous and soft tissue radiographic parameters utilizing a larger sample size than previously studied. This information could potentially guide patient counseling of expectations regarding postoperative outcome and assist surgeons in optimizing shoulder balance correction during arthrodesis. Methods: This study will be a retrospective, chart review of patients treated for adolescent idiopathic scoliosis with spinal fusion at a single center. We will be collecting radiographic measurements to assess pre- and postoperative spinal, thoracic, and shoulder alignments. Research team members will individually collect data each patient’s imaging with at minimum 2 years of postoperative radiographic assessment. Data will be stored in REDCap. Results: Conclusions:
Identifying Top Gene Contributors to Triple Negative Breast Cancer Health Disparities Among African American Women: A Machine Learning Approach
(2019-03-05) Liu, Jin; Hayatshahi, Hamed; Morid, Mohammad Amin; Green, Amyia; Fluker, Kenneth Jr.; Ahuactzin, Emilio; Radler, Charlene
Purpose: Triple Negative Breast Cancer (TNBC) is a breast cancer subtype which multiple studies have shown to be disproportionately prevalent among premenopausal African American women. The factors contributing to the TNBC health disparities remain unclear. Methods: Here, we developed a highly accurate, reproducible machine learning classification model that used patient gene expression values as predictor attributes to classify 100 TNBC patients as either African American or non-African American. Results: By using weighting methods and comparison of classification performance at varying levels of attributes, our study identified a subset of genes able to accurately classify TNBC patients by race. Intriguingly, the top genes of this subset are linked to diabetes, indicating that diabetes may associate with the TNBC health disparities. Conclusions: Our study demonstrated the factors contributing the TNBC health disparities and provided a subset of genes that may be targetable for precision medicine development to address disparity of TNBC among the African American female population.
Break a Sweat, Mend Your Mind: Exercise and Mood Among Adolescents
(2019-03-05) Thompson, Erika; Harrison, Samantha
Purpose: The prevalence of depression in adolescents is rising, and regular exercise has been reported to have a decreasing effect on incidence of depressed mood in meta-analyses of adult interventions. There is a need to explore this association among adolescents. The purpose of this study was to examine the association between exercise and mood among United States adolescents responding to the Youth Risk Behavior Survey (YRBS) 2017. Methods: YRBS is a nationally representative sample of 9th through 12th grade students (N=14,765), and was restricted to an analytic sample (N=10,789). The outcome of interest was depressed or low mood (yes/no to feeling sad or hopeless in the past 12 months), and the exposure was physical activity (yes/no to being physically active for at least 60 minutes on five or more days in the past week). Covariates included: age, sex, race/ethnicity, physical education class attendance, sports team participation, and hours of sleep. SAS version 9.4 was used to perform survey-weighted descriptive estimates and crude and adjusted logistic regression models. Results: Overall, 47.5% of participants reported being physically active, and 31.3% reported feeling sad or hopeless in the last year. Respondents who reported physical activity were less likely to have reported feeling sad or hopeless when compared to those who were not physically active (OR=0.68, 95%CI 0.59, 0.79). When adjusting for age, sex, race/ethnicity, physical education class attendance, sports team participation, and hours of sleep, the association was no longer statistically significant (aOR=0.93 95%CI 0.80, 1.10). Conclusions: While an association between exercise and depressed mood was not observed in this cross-sectional study, further research is needed into the risk and protective factors for depression in adolescents due to the rising prevalence of the disorder.
Assessing Women’s Perceptions of Their HPV and Cervical Cancer Knowledge
(2019-03-05) Matthes, Sarah; Thompson, Erika; O'Neal, Morgan
Purpose: This project aimed to assess women’s HPV and cervical cancer knowledge and women’s perceptions of their knowledge. With recent changes to cervical cancer screening guidelines in the US, it is an opportune time to assess women’s knowledge of cervical cancer and its primary cause, human papillomavirus (HPV). Women’s knowledge of HPV and cervical cancer may be beneficial for reducing anxiety and uncertainty with cervical cancer screening. Moreover, there is a need to examine if women’s perceptions of their knowledge align with knowledge levels, which may present opportunity for health education. Methods: An online survey (n=812) of women 30-65 years old without hysterectomy was conducted in June 2018. Survey items assessed knowledge of HPV (16-items), cervical cancer (12-items) and perceived ease of understanding cervical cancer screening information (Likert scale). Knowledge scores were created from correct responses to true/false questions. Descriptive frequencies for items and Kruskal-Wallis tests were used in SAS 9.4. Results: Most women (70%) perceived understanding cervical cancer screening information as easy or very easy. The mean HPV knowledge score was 8.10 (out of 16). The mean cervical cancer knowledge score was 6.88 (out of 12). Women’s perceptions of their understanding were significantly associated with HPV and cervical cancer screening knowledge (p Conclusion: Results indicate that women have an accurate perception of their cervical cancer screening knowledge. Additionally, the association between HPV and cervical cancer was noted by participants. Increasing knowledge of the high likelihood of HPV infection may increase screening willingness. Education that the clinical course of cervical cancer is slow and preventable may reduce testing anxiety. More public information on no and low cost screening resources may also help increase screening. These gaps represent patient and provider education opportunities that may assist in increasing adherence to cervical cancer screening recommendations.
Glucocorticoid-induced glaucomatous neurodegeneration is associated with demyelination of optic nerve axons and infiltration of immune cells
(2019-03-05) Kasetti, Ramesh; Patel, Pinkal; Zode, Gulab; Maddineni, Prabhavathi
Purpose: Ocular hypertension (OHT) is a serious side effect of glucocorticoid (GC) therapy and if untreated, it can leads to secondary open-angle glaucoma. However, the precise mechanism of GC-induced glaucomatous neurodegeneration is not understood largely due to lack of proper mouse model that exhibits glaucomatous neurodegeneration similar to human glaucoma. Using a novel mouse model of GC-induced OHT, we determined whether prolonged GC-induced OHT leads to glaucomatous neurodegeneration and further explored the pathological mechanisms of axonal degeneration and role of neuroinflammation in glaucoma. Methods: C57BL/6J mice were injected with either Dexamethasone Acetate (Dex) or Vehicle (Veh) via periocular-route, once a week for 10-weeks. IOP was measured every week and glaucomatous neurodegeneration was examined at 5 and 10-weeks of treatment using pattern ERG (pERG), whole mount retina staining with RBPMS antibody and PPD staining and transmission electron microscopy (TEM) for optic nerve (ON) degeneration. Reactive astrocytes, axonal cytoskeleton changes and immune cells at ON head (ONH) were assessed by immunostaining. Cholera toxin B (CTB) was used to trace axon anterograde transport deficits. Results: Periocular injections of Dex caused significant and prolonged IOP elevation (Δ ≥3.5-5 mmHg) and outflow facility reduction (by ~40%) compared to Veh-injected mice. Dex-induced OHT was associated with increased ECM deposition and cytoskeleton changes in the TM. Interestingly, Dex-induced sustained OHT led to glaucomatous neurodegeneration after 10 weeks of treatment including significant functional and structural loss of RGCs as evident from reduced pERG amplitudes (10µV v/s 25µV) and ~36% loss of RGCs in whole mount retina RBPMS staining. Neuronal labelling with CT-B demonstrated anterograde transport deficits in Dex-treated eyes, with increased reactive astrocytes at ONH. We also observed ~40% loss of optic nerve axons in PPD staining. TEM analysis of ON further demonstrated chronic demyelination of optic nerve axons with mitochondrial accumulation and immune cells infiltration, which was further confirmed by immunostaining. Conclusions: These data highlights that GC-induced OHT causes inflammatory demyelination of the optic nerve axons, which results in glaucomatous neurodegeneration.
The Association Between Human Papillomavirus Vaccination and State Medicaid Expansion
(2019-03-05) Al-Nahi, Ali; Certeza, Justinne; Fernandez, Jazmin; Hoffman, Katherine; Thompson, Erika; Hoff, Brandon
Purpose: The human papillomavirus (HPV) vaccine is recommended for US adolescents 11-12 years of age. The HPV vaccine is currently covered for children enrolled in Medicaid through age 20. After the passage the Affordable Care Act in 2010, states were given the option to expand Medicaid eligibility to 138% of the federal poverty level, yet as of December 2017, only 36 states have elected to expand their Medicaid program. This study examines the association between Medicaid expansion and HPV vaccination among US adolescents. Methods: This cross-sectional study was conducted using data from the National Immunization Survey – Teen, 2017 (N=20,949). Logistic regression was used to model provider-reported HPV vaccination up-to-date status predicted by state Medicaid expansion while adjusting for the effects of sex, race/ethnicity, maternal education level, household income, and type of health insurance. All analyses were conducted using SAS Studio 3.7 Enterprise Edition with survey weighting procedures. Results: 52% of adolescents in this study were up-to-date on the HPV vaccine. Adolescents who lived in states that expanded Medicaid [OR = 1.51, (95% CI: 1.36, 1.68)] were more likely to be up-to-date on the HPV vaccine than adolescents who lived in states that did not expand Medicaid. Females [OR = 1.50, (95% CI: 1.35, 1.66)], Non-Hispanic Blacks [OR = 1.23, [95% CI: 1.09, 1.54)], and Hispanics [OR = 1.67, (95% CI: 1.42, 1.96)] were more likely than to be up-to-date on the HPV vaccine than males and Non-Hispanic Whites, respectively. Individuals who were enrolled in Medicaid [OR = 1.19, (95% CI: 1.02, 1.39)] were more likely to be up-to-date than those with private insurance. Conclusion: The results of this study indicate a positive association between Medicaid expansion and HPV vaccination. However, Medicaid expansion is only one of many health policy initiatives that can affect HPV vaccination. Recent research has suggested that state-level policies (e.g., school-entry requirements, policies permitting vaccination in pharmacies, classroom sex education policies, and parental education mandates) are significantly associated with uptake of the HPV vaccine in adolescents. Further research should be conducted to analyze the combinatorial effects of multiple health policies on HPV vaccination.
Health Literacy: Obstacles to Quality Healthcare in Tarrant County
(2019-03-05) Cooksey, Luke; Ahn, Soongjin; Rose, Sushyreta; Hubbard, Daniel; Vo, Russell
Purpose: To identify the primary barriers to health literacy and the resources available to community members to optimize health literacy. Background & Conclusion: Health literacy is defined as the degree to which individuals have the capacity to obtain, process, and understand basic health information and the services needed to make appropriate health decisions. According to the U.S. Department of Health & Human Services, only 12% of persons in the United States are classified as proficient, meanwhile more than 25% of persons ([greater than] 77 million people) in the United States experience difficulty with mundane health tasks like following the directions on a prescription label. There are a variety of influencing factors that determine a person’s overall health literacy including demographic factors, biological, and psychosocial factors. There are four main demographic factors that influence health literacy: poverty status, race/ethnicity, education level, and age. Patients that are below the poverty status line, have minority status, have achieved less than a high school education or its equivalent, and/or are above 65 years of age are at an increased risk of possessing less than proficient health literacy. The primary biological and psychosocial aspects that influence health literacy include a patient’s lifestyle and occupation, language competency, culture, and/or cognitive ability. In Tarrant County, there are a number of accessible and expedient resources available to healthcare professionals and members of the community to optimize health literacy and subsequently, health outcomes. The resources available include: United Way of Tarrant County Health Symposium, North Texas Area Community Health Centers, Tarrant County Diabetes Collaboration, Healthy Aging and Independent Living Initiative, Health Education and Literacy Project Consortium, UNT Health Science Center, and of course, your primary care provider.
A Computer-Based Approach to Developing Diagnostic Rules
(2019-03-05) Papa, Frank; Parikh, Tiraj
Purpose: In 2015, the National Academy of Medicine published a report revealing that diagnostic error may be America’s third leading cause of death and responsible for the majority of paid medical malpractice claims. Medical education researchers are now looking to the learning sciences for theories that might support improvements in the diagnostic performance of tomorrow’s health care providers. One such theory, called “Dual-Process Theory”, suggests that people utilize two distinct approaches to diagnostic reasoning: pattern recognition and analytical reasoning. To date, researchers have paid little attention to how we reason analytically. Dual-process theorists suggest that analytical reasoning is, in part, predicated upon a clinician’s knowledge of diagnostic rules. These rules encompass knowledge in the form of experientially-based, statistically-framed estimates of the frequency with which a given disease is associated with each of its characteristic findings. The purpose of this project is to produce a computer-based training tool which supports learners in how to analytically reason via the acquisition and application of conditional probability (CP) derived diagnostic rules. Methods: This tool will have four components: 1) a display of CP derived diagnostic rules associated with signs and symptoms most likely to be linked to a given clinical presentation 2) a set of interactive tools enabling learners to identify which of those rules are most robust in ruling in/out the various differentials, 3) a set of practice cases where learners are given multiple opportunities to apply these CP derived rules, and 4) interactive screen prompts designed to guide the students in developing a cognitive strategy to apply high-yield rules to diagnose a multitude of test cases. Results: The exhibitor will demonstrate a tool which: 1) displays disease by sign/symptom CPs, 2) enables their rearrangement (by history & physical, breadth by feature strength, and depth by selected differential) as the basis for formulating diagnostic rules, and 3) functions which support the construction of a diagnostic strategy. Conclusions: After completion of the described educational tool, the authors will execute an IRB approved study involving students in a year 2 systems course, and a treatment/control research design.
Intracellular Chloride Regulation of Supraoptic Vasopressin Neurons during Salt Loading
(2019-03-05) Farmer, George; Little, Joel; Bachelor, Martha; Cunningham, J. Thomas; Balapattabi, Kirthikaa
Purpose Salt loading (SL) increases intracellular chloride concentration [Cl]i, impairing GABAA inhibition of arginine vasopressin (AVP) neurons in the supraoptic nucleus (SON) of hypothalamus. But the regulatory mechanisms leading to increased [Cl]i is not completely understood. Based on previous studies, we hypothesize that SL activates tyrosine receptor kinase B (TrkB) and downregulates K+/Cl- co-transporter 2 (KCC2) membrane expression. Downregulation of KCC2 decreases the efflux of chloride, Cl ion causing increase in [Cl]i in SON AVP neurons. In this study, we combined virally mediated ClopHensorN, a relatively new ratiometric Cl imaging technique with capillary based Simple Wes to record changes in [Cl]i and specifically detect KCC2 protein expression in individual SON AVP neurons. Methods Adult male Sprague Dawley rats were bilaterally injected in the SON with rAAV2-0VP1-ClopHensorN. The ClopHensorN (Addgene Plasmid #50758) was packaged in an AAV2 vector with an AVP promotor (Addgene Plasmid #40868). After 2 weeks, the rats were given either water or 2% NaCl to drink for 7 days. At the end of the protocol, the rats were anesthetized with inactin and their SONs were dissociated. The cells were plated on coverslips and placed in a perfusion bath on an inverted microscope for ratiometric live cell imaging. ClopHensorN positive neurons were tested for decrease or increase in [Cl]i to focal application of GABAA agonist muscimol (100uM). After imaging, individual neurons were collected by aspirating into a patch pipette to verify KCC2 and ß-Actin protein expression. Protein Simple Wes (12-230kDa matrix) was used to identify and quantitate very low concentration of protein from single neuron. Data were analyzed by Chi-squared test and one-way ANOVA with Bonferroni comparisons. Results Muscimol application to SL SONs either significantly increased Cl efflux (p Conclusion Salt loading increases [Cl]i in SON AVP neurons through TrKB-KCC2 mechanism.

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