2013

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EFFECT OF WATER DEPRIVATION ON KCC2 EXPRESSION IN HYPOTHALAMIC VASOPRESSIN NEURONS IN RAT
(2013-04-12) Knapp, Blayne
Purpose: Argininge Vasopressin (AVP) is a neurohypophyseal hormone that contributes to body fluid homeostasis by regulating plasma fluid and electrolyte composition. It is released from the posterior pituitary (PP) by magnocellular neurosecretory cells (MNCs) located within the supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus. The regulation of AVP release is critical for maintaining blood volume and blood pressure, and although the molecular mechanisms of AVP regulation are not fully understood, we do know that it is partially due to the vital balance of synaptic excitatory and inhibitory inputs that determine the relationship between plasma osmolality and AVP release. Dysregulation of this system and the resulting disturbances of water and electrolyte balance can lead to increased morbidity associated with disease states such as heart and liver failure. This is why it is critical for us to elucidate the molecular mechanisms involved with its physiological control and its inappropriate release in disease states. Models of water deprivation represent a physiological challenge that requires sustained release of AVP from the PP into circulation as a means of maintaining body fluid homeostasis. We attempt to address the gaps that remain controversial or unexplained in our current understanding of AVP regulation by measuring changes in the expression of extruder KCC2 in water deprived and euhydrated adult male rats and measuring its effects on inhibitory GABAergic neurotransmission in AVP MNCs. Methods: Using laser capture microdissection (LCM), AVP MNCs were harvested from the SON and PVN of euhydrated and 48 hour water deprived adult male rats and reverse transcriptase polymerase chain reaction (RT-PCR) studies were used to test for changes in KCC2 message. Western blot protocols were used to measure changes in protein expression. Results: We observed a significant elevation in KCC2 mRNA expression in AVP cells of the SON (WD 2.5 ± 0.52; Control 1.0 ± 0.06, p<0.05) but not in the PVN (WD 3.5 ± 1.7; Control 1.0 ± 0.1). Immunofluorescence demonstrated the colocalization of KCC2 and AVP in the SON. Conclusions: Increased expression of KCC2 could be associated with decreased intracellular Cl- in AVP neurons in the SON, thereby serving to maintain or enhance the inhibitory tone of AVP neurons in the SON but not the PVN during WD.
FACTORS AFFECTING RURAL STUDENTS' APPLICATION AND ADMISSION TO MEDICAL SCHOOL
(2013-04-12) Cummings, David
Purpose: To identify factors that influence the medical education of rural undergraduates and increase the number of graduates that practice in rural communities. Objectives 1.Develop a valid survey tool to evaluate and measure the barriers of rural students that affect their decision to apply and gain admission to medical school. 2.To examine the barrier and support factors associated with the medical school application process that affects premed undergraduate rural students. 3.To examine the barrier and support factors associated with the medical school admissions process and outcome that affects applicants to TCOM. Methods: The research design for this study is primarily observational. Descriptive statistics were generated using SPSS© version 19 and crosstabs were used for comparisons. Hypothesis testing was performed on relevant comparisons. Non-Parametric analysis methods including Chi Squared and the Mann-Whitney Rank Sum Test were performed to test for significance among comparisons. A significant alpha level of .05 will be used for all significance tests. Results: For rural students, the level of positive influence from "other relatives" was statistically significant (p value= .018). Rural status may also be associated with the perceived level of helpful advice given to the students by selected persons. Rural students did show more helpful feedback was provided to them by their premedical/prehealth advisor than non-rural counterparts.The association was not significant at the .05 level (p value=.089). For rural students, the top three obstacles include prerequisite courses, MCAT preparation, and MCAT score. Non rural students share the same three top choices, except healthcare experience and prerequisite classes tied for third largest obstacle. MCAT score accounted for the largest difference between the groups but was not statistically significant (p value=.75). Conclusions: Factors exist that can impair or assist undergraduates in achieving their goals of applying to medical school or being accepted into a medical program. Rural students may experience these factors differently than their non-rural counterparts. Determining which persons and which programs are most helpful is a necessity. A small sample size and a lack of diversity within our pre-test sample make it difficult to generalize our findings to the target population. A pilot study with a sufficient number of diverse respondents must be conducted to evaluate the contributing factors accurately.
INVOLVEMENT OF P38 MAPK IN REACTIVE ASTROGLIOSIS INDUCED BY ISCHEMIC STROKE
(2013-04-12) Roy Choudhury, Gourav
Purpose: Reactive astrogliosis is an important response during early phase of cerebral ischemia but as time progresses; these activated astrocytes develop into a glial scar. During acute phase of ischemia, astrocyte activation is beneficial as it limits the spread of infarct however in long term the glial scar developed becomes a barrier to migrating axons and hinder the recovery process. The hallmark of astrogliosis is an increase in the expression of GFAP (Glial fibrillary acidic protein). However the signaling events underlying these phenomenons have not been yet clearly elucidated. p38MAPK, a stress signaling Mitogen activate protein kinase plays an essential role in inflammation and has been widely reported to be activated during ischemic injury. Since inflammation is major determinant of events after ischemic injury in brain, we hypothesize that p38 MAPK plays a critical role in reactive astrogliosis after ischemic injury and its inhibition attenuates glial scar formation Methods: For in vitro studies rodent primary astrocytes were used and were subjected to Oxygen-glucose deprivation (OGD) for 3h. p38MAPK's role in astrocyte activation was determined pharmacologically with a p38 inhibitor (SB 239063) and genetically by an astrocyte specific p38 knockout. 24 hours following insult and the expression of GFAP was determined using Western blots. Wound healing and Transwell assay were used to determine role of P38 in astrocyte migration. For in vivo studies astrocyte specific conditional p38 knockout mice (p38KO) were used. Transient or Permanent middle cerebral artery occlusion (tMCAO or pMCAO) was performed to model ischemic stroke. Walk initiation, Negative geotaxis and Ladder rung walking test were used to determine motor dysfunction after MCAO. Astrogliosis morphometric analysis was to quantify glial scar in GFAP stained brain sections Results: In primary astrocyte cultures, hypoxia and scratch injury-induced astrogliosis was attenuated by both p38 inhibition and knockout of p38 MAPK. In vivo studies showed that p38KO mice after permanent MCAO had a significantly smaller glial scar compared to their wild type (WT) littermates. Results also indicated that p38KO mice performed significantly better in behavioral studies compared to their WT only in tMCAO Conclusions: p38MAPK plays an essential role in evolution of glial scar after ischemia and its inhibition attenuates glial scar formation. P38 inhibition significantly improves motor dysfunction in tMCAO but the protection is lost in pMCAO
ANALYSIS OF IMPACT SCORES OBTAINED AS A FUNCTION OF REVIEW CYCLES (FROM JUNE 2010 TO JUNE 2012 REVIEW CYCLES)
(2013-04-12) Tan, Debra
Purpose: To examine the trend of scientific quality of research grant applications submitted to AHRQ with time, we assessed the overall impact scores provided by each of 5 standing study sections as a function of times during the past 7 review cycles (from June 2010 to June 2012). Methods: As at the NIH, the Scientific Peer Review Committees at AHRQ use 9 points overall impact score system to evaluate the scientific merit of research grant applications submitted to AHRQ for funding opportunity. This analysis is based upon the enhanced score criterion http://grants.nih.gov/grants/guide/notice-files/NOT-HS-10-002.html using the final impact scores assigned to the applications that were discussed at the review meetings from five study sections and Special Emphasis Panel (SEP) that were reviewed from June 2010 to June 2012 (a total of 7 review cycles). The data used in this analysis was from the National Institutes of Health (NIH) Query View & Report Database (QVR system). Microsoft Excel and SPSS were the tools used for analysis. Results: The means impact scores trend to increase with time in terms of review cycles (from June 2010 to June 2012). The means impact scores trend to increase with time in terms of review cycles (from June 2010 to June 2012). For example, for the HCRT, HQER or HSR study section, the means impact scores decrease to a lowest values of about 31-35 the exception of February 2011 review cycle meeting. The means of overall impact scores gradually increased to higher values at the subsequent review cycles to about 38 to 53 for all 5 study sections. The means for the June 2010 cycle ranged from 36.26 - 40.76 and the means rose to upward trend for the June 2012 cycle at 38.48 - 53.46 range showing an upward trend. Although the mean values of impact scores implicated an upward trend from June 2010 to June 2012, there was no statistical significance among these mean values. Conclusions: Our analysis of impact scores among study sections found no statistically significant differences, indicating that the AHRQ peer review process is consistent in terms of quality of the scientific review among study sections. Our findings could provide useful information to the AHRQ leadership team, as well as the extramural health services research community regarding the scientific peer process for grant applications submitted to AHRQ for funding opportunity.
THE ASSOCIATION BETWEEN AGGRESSION AND DHEA-S
(2013-04-12) Marshall, Hayley
Purpose: The purpose was to assess the association between aggression, including the subcategories of physical, verbal, anger, and hostility aggression, with serum DHEA-S levels in non-Hispanic Caucasian (NHC), non-Hispanic African American (AA), and Hispanic (H) women, aged 20-40 years. Methods: Data were obtained from the Racial/Ethnic Differences in Stress Age Among Women Study. This study included women 20 - 40 years of age who were not pregnant and not taking glucocorticoids. Participants also did not have cancer; endocrine disorders (e.g. Diabetes Mellitus); thyroid, parathyroid, or adrenal gland disorders; or immunologic disease (e.g. HIV, AIDS, Lupus). Participants completed self-reported questionnaires including the Aggression Questionnaire. DHEA-S levels were measured via a blood draw. Five simple linear regression models were analyzed with each category of aggression as the independent variable and DHEA-S as the dependent variable. Multiple linear regressions included the aggression category, age, and race/ethnicity. Log-transformed DHEA-S was utilized to achieve normality. Statistical significance was assessed at alphad0.05. Results: A total of 70 women with mean age of 29.4(sd=5.4) were included. There were 23 NHC, 21 AA, and 27 H participants. In crude analysis, an increase in total(p=0.019) and verbal aggression (p=0.008) was associated with a decrease in logDHEA-S. The association for physical aggression approached significance (p=0.059). After controlling for age and race/ethnicity, an increase in verbal aggression (p=0.021) was associated with a decrease in logDHEA-S. A borderline association was observed for total aggression (p=0.054). Compared to NHC, being AA was associated with a decrease in logDHEA-S in models with total, physical, and anger aggression. The association approached significance in the models for verbal and hostility aggression. An increase in age was associated with a decrease in logDHEA-S in all models. Conclusions: Results indicate there is interplay between the psychosocial factors of physical, verbal, and total aggression (the first two being physical manifestations of aggression) with DHEA-S levels. Since DHEA-S is associated with many (non)physiological processes, it is important that future clinicians understand how these biopsychosocial aspects of life can influence each patient individually. If clinicians can understand these relationships, then they can work with their patients towards a goal of both physical and psychosocial well-being.
EFFECTS OF METABOLIC ACIDOSIS ON MOTOR AND COGNITIVE FUNCTION IN YOUNG AND AGED MICE
(2013-04-12) Kindle, Robbyn
Purpose: Metabolic acidosis is defined as a reduction of serum pH below 7.4 due to the inability of the kidneys to remove an adequate proportion of hydrogen protons (H+), and can be a symptom of diabetes, kidney disease, and aging. The effects of acidosis on the nervous system are not well understood, and little research has been done to establish those effects and their potential role in cognitive decline. Methods: Four- and twenty-month-old male C57BL/6J mice (n=8) were fed either a control diet or the control diet supplemented with 2% ammonium chloride (NH4Cl) to induce metabolic acidosis. Urine pH was measured weekly to insure inducement of acidosis in the NH4Cl supplemented diet groups. After 4 weeks of pre-treatment, the mice were tested for various functional tasks and remained on their respective diet during behavioral testing. The tests were done in the following order: locomotor activity, reflexes, wire suspension, bridge walking, active avoidance (T-maze), and Morris water maze. Results: Overall, urine pH of the mice on the NH4Cl diet was decreased compared to control mice. Though the NH4Cl diet did not seem to affect the weights of the young mice, a significant decrease was seen in the aged mice. Aged mice on the NH4Cl diet had increased spontaneous activity and better performance on motor tasks. On spatial learning and memory, the NH4Cl mice learned to locate the platform more efficiently than their age-matched controls. In general, the NH4Cl mice took fewer trials to reach the criteria of avoidance and discrimination. Conclusions: Interestingly, the data suggest a potential benefit on motor and cognitive function of a mild acidosis in young and aged mice. More studies will solidify these observed effects and identify a potential mechanism by investigating acid sensing ion channel concentration in various brain regions through immunoblot analysis.
EFFECTS OF APOE GENOTYPE, ANTIOXIDANTS AND EXERCISE ON MOTOR AND COGNITIVE FUNCTION
(2013-04-12) Chaudhari, Kiran
Purpose: The ɛ4 allele of apolipoprotein E (ApoE) has been associated with increased risk for development of late-onset Alzheimer's disease (AD). To prevent appearance of brain dysfunction, a healthy lifestyle, such as exercising and eating antioxidants, is often recommended. Physical activity has been shown to have an allele-specific beneficial effect on cognition in humans and rodents. Antioxidant therapy is often suggested to improve brain function, as increased oxidative stress has been correlated with brain dysfunction, especially in ɛ4 carriers. Health conscious individuals are likely to combine exercise with antioxidant intake to increase protection, however recent studies have indicated a negative interaction of these two factors. In some cases, antioxidant intake abolished the beneficial effects of exercise. Our study aimed at determining the nature of the interaction between exercise and antioxidants on functional outcomes in a model of increased AD risk. Methods: Young male and female mice, expressing the human ApoE3 or E4, were placed under one of the treatment: Sedentary/control diet (SedCon), Sedentary /antioxidant-rich diet (Vitamins E and C; SedEC), Exercise/control diet (EXCon), Exercise/ antioxidant-rich diet (EXEC), for 8 weeks prior to behavioral testing. Behavior testing includes running co-ordination (rotorod), spatial learning and memory (Morris Water Maze)and discriminative avoidance and cognitive flexibility (T maze). Results: In a coordination test, the E3 mice performed better than the E4 mice, and a significant improvement was observed with the ExEC treatment in males E3 and females E4. Better spatial learning was detected with EXEC in E3 females but not in E4. In males EX impaired learning index in E3 males. In active avoidance acquisition session, learning performance was improved with EX and EXEC treatment in E3 male, and with EXCon treatment in female E4, whereas cognitive flexibility was improved in both male and female in E3 by all the treatments but not in E4. Conclusions: These results in young mice provide an indication that genotype and sex are critical determinants in the functional outcomes of the treatment.
MICRO RNA MEDIATED REGULATION OF MIEN1 IN PROSTATE CANCER
(2013-04-12) Rajendiran, Smrithi
Purpose: MIEN1 is a membrane bound signaling molecule that triggers downstream signaling through the AKT/NF-𝛋B pathway by up-regulating key proteases and has a role in migration and invasion of cancer cells. The overall objective of this study is to identify the mechanisms that lead to the differential regulation of MIEN1 in normal and cancer cells. Though there are multiple mechanisms that are commonly studied, here, we propose to focus on the post-transcriptional regulation of MIEN1. Our data leads to the hypothesis that MIEN1 is post-transcriptionally regulated by a specific microRNA (miR) that is down-regulated in cancer, thus explaining aberrant increased expression of MIEN1 in cancer. Methods: We have performed miR in silico analysis, expression profiling, northern blotting, qPCRs, western blotting, luciferase reporter assays, migration and invasion assays, colony formation assays and stability assays to determine the effects of the miR on different aspects of MIEN1 regulation. Results: Our data indicate that MIEN1 is post-transcriptionally regulated by a specific miR which is lost in cancer cells. This miR is highly expressed in normal cells compared to a decrease in various cancer cells and this expression is inversely correlated to the expression of MIEN1. Introduction of the mimic (precursor) or inhibitor (antagomiR) led to a decrease or increase in MIEN1 expression respectively at both the RNA and protein levels. The downstream effectors were also similarly affected. The luciferase activity significantly reduced when the 3'UTR of MIEN1 was transfected with the target miR compared to the control miR, validating the direct binding of the miR. The miR decreases the migration and invasion of cells as well as the stability of MIEN1 RNA. There was a significant reduction in the colony formation capabilities and the morphology of the colonies differed in cells that were transfected with the miR along with a decrease in E-cadherin, suggesting potential involvement of the miRNA in reducing epithelial to mesenchymal transition and hence inhibiting metastasis. Conclusions: Our results demonstrate that aberrant expression of MIEN1 in cancer is attributed to a specific miR. We are currently exploring the potential of using this miR as a biomarker in prostate cancer. Since the importance of MIEN1 as a key signaling molecule in cancer is well established, understanding the mechanisms involved in its regulation will aid in designing novel and effective therapeutic strategies to treat cancer patients.
IMPORTANT ROLES OF EXOSOMES IN HIV-1 TAT-MEDIATED NEUROTOXICITY
(2013-04-12) Rahimian, Pejman
Purpose: Our purpose is to determine the significance of astrocyte-released exosomes in regulation of HIV-1 Tat neurotoxicity. We hypothesize that the exosomes produced by astrocytes contribute to Tat neurotoxicity. Methods: Primary astrocyte cultures were prepared from the embryos of brain-specific and doxycycline-inducible Tat-transgenic and wild type mice and treated with 5 ug/ml doxycycline for 3 days to induce Tat expression. The Tat transgenic mice express HIV Tat gene under the dual control of a doxycycline-inducible promoter and the glial fibrillary acidic protein (GFAP) gene promoter. Addition of doxycycline induces the expression of HIV-1 Tat protein in mouse astrocytes. Supernatants from doxycycline-treated cultures were collected and incubated with SHSY5Y neuroblastoma cells for 3 days. MTT assay was performed to determine the survival of the neurons. Briefly, tetrazolium reagent was added to cultures and incubated for 5 hours in 37oC. The reduction of this reagent by NAPDH-Oxidase in the mitochondria of healthy cells will form a blue color which can be measured spectrophotometrically after dissolution with acid-isopropanol. The intensity of the blue color indicates the number of healthy cells. To determine the roles of exosomes in Tat-induced neurotoxicity, astrocyte cultures were first induced with doxycycline, the culture media were replaced with fresh complete media, the cell continued to culture for 48 hours in the presence of 5 uM or 10 uM GW4869, an inhibitor of neutral sphingomyelinase which is critical for the production of exosomes in astrocytes. The supernatants from GW4869-treated cultures were collected and determined for its neurotoxicity using the MTT assay described above. Results: Supernatants of doxycycline-induced Tat-transgenic astrocyte cultures decreased the survival of neuroblastoma cells compared to those of wild type astrocytes. Inhibition of exosome production in doxycycline-treated astrocytes with GW4869 improved the survival of neuroblastoma cells compared to those that were not treated. Conclusions: These findings confirmed that Tat expression in astrocytes in the absence of HIV infection caused neurotoxicity and showed for the first time that exosomes produced from Tat-expressing astrocytes were involved in induction of Tat neurotoxicity.
MUCINOUS ADENOCARCINOMA LOCATED ON THE RIGHT LABIA
(2013-04-12) Carrizales, Enrique
Purpose: To present a case report and review of the literature of a patient with a well differentiated mucinous adenocarcinoma located on the right labia. Methods: A 52 year old African American female, gravida 3, para 2, presented to the clinic with a 8 month history of a pea sized mass on her right labia that had increased in size and tenderness. On physical exam the nodule was located at the internal middle third of the labia minora. The nodule was removed superficially and a diagnosis of a mucinous adenocarcinoma was made. Results: The removed mass was an irregular 1.0 x .8 x .5 cm fragment of gray-white soft tissue with an attached 0.6 x 0.4 cm ellipse of pale tan skin and a 2.1 x 1.5 x 0.5 cm aggregate of gelatinous translucent tan and red-tan mucoid material. Pathology revealed that the mass did not have free margins. Pathology of the labial mass biopsy revealed a well-differentiated mucinous adenocarcinoma with coexpression of mammaglobin and GATA-3 most likely of eccrine origin. Considering the coexpression of mammoglobin and GATA-3, the tumor is presenting a phenotype similar to mucinous carcinoma arising from the breast. However, a bilateral mammogram showed no evidence of malignancy. The decision was made to undergo a radical excisional procedure with a sentinel lymph node biopsy on the right side to determine lymphatic spread of the tumor. Conclusions: Sweat gland tumors of the vulva are a rare type of cancer. There is a lack of clear evidence in the literature regarding this condition. Between 1958 to 2009, 12 patients were described receiving treatment. Of the 12 patients five had recurrence of the cancer, three with distant metastatic disease and two with a localized recurrence. The literature states that radical resection of the tumor with clear margins results in the best outcomes. The literature is unclear as to whether adjunct therapy, radiotherapy or chemotherapy, has added benefits. This is particularly true in the case of radiotherapy as current literature suggests that primary sweat gland tumors tend to be resistant to this modality. In view of coexpression of mammaglobin GATA-3 and the absence of any evidence of breast cancer the diagnosis of a primary sweat gland tumor of the vulva was made.
COLORECTAL CANCER SCREENING IN EASTLAND & LIMESTONE, TEXAS: PATIENT AWARENESS
(2013-04-12) McKenzie, Laura
Purpose: The U.S. Preventive Services Task Force (USPSTF) has designated colorectal cancer screening as a Grade "A" recommendation. Despite such strong recommendations, recent studies indicate that rural populations are being screened less successfully than urban populations. The studies show that colorectal cancer screening detects more advanced disease in rural populations than in urban populations. Previous studies have also identified different factors affecting colorectal cancer screening, one of them being knowledge about colorectal cancer and screening guidelines. The purpose of this study was to assess the relationship between knowledge of colorectal cancer and knowledge of colorectal cancer screening with actual screening by colonoscopy in a patient population in Eastland and Limestone Counties. Methods: A cross-sectional study was conducted by administering a survey to assess citizen's public knowledge concerning colorectal cancer and screening. The survey consisted of questions related to colorectal cancer screening knowledge and behaviors. Questions were taken from the Behavioral Risk Factor Surveillance System Survey, as well as other published literature regarding knowledge of colorectal cancer. The survey also contained demographic information. Participants age 18 and older were recruited in primary care clinics in Eastland and Limestone Counties. Descriptive statistics were performed for demographic variables (gender, age). A knowledge of colorectal carcinoma (CRC) score and a knowledge of CRC Screening were calculated. Logistic regression was performed to analyze the relationship between both types of knowledge and being screened by colonoscopy. Results: Of the 109 respondents, 68.8% ( n= 75) were 50 years or older and 72.5% (n=79) were female while 25.7% (n=28) were male. In this study 58.5% scored the survey maximum score of 3 for Knowledge of CRC and 19.8% the maximum score of 5 for knowledge of CRC screening. The odds of being screened by either colonoscopy or sigmoidoscopy in those 50 years or older significantly increased (OR = 1.82; 95% Confidence Interval [CI], 1.08 to 3.05) when combined knowledge score of respondents increased by one unit. The odds for screening is also increased significantly (OR = 11.9; 95% CI, 1.06 to 132.7) in those employed compared to those not employed. Conclusions: The results show that colorectal screening was higher in respondents with greater knowledge about CRC and CRC screening.
PHYTOESTROGENS IN THE BRAIN
(2013-04-12) Brock, Courtney
Purpose: Soy is one of the top ten herbal supplements taken in the United States. It is generally marketed as a safe and natural way to improve a diverse array of disease conditions such as osteoporosis and to improve menopausal symptoms. Its efficacy, however, has not been completely validated. Genistein, which is a major constituent of soy, is a phytoestrogen, and is thought to elicit some of soy's beneficial effects through activation of estrogen receptors (ER). Despite its wide use, it is currently unclear how genistein might affect the brain. We hypothesize that like estrogen, genistein can be neuroprotective but its capacity to do so is dependent on the availability of "intact" ER-brain derived neurotrophic factor (BDNF) signaling. We have also tested the hypothesis that because ER expression may change as a function of age and sex, such changes may alter genistein's capacity to influence neuroprotective proteins such as BDNF. Methods: This hypothesis was tested using complementary in vitro and in vivo models. For our in vitro experiments we used mouse cerebral cortical explants. Genistein was applied to the cultures at ER activating concentrations. Glutamate was then applied as an excitotoxic insult to induce cell death. Cell death was quantified by measuring the amount of lactate dehydrogenase (LDH) released by the cells into the media. To corroborate our in vitro data, we assessed whether age related changes in ER expression affect genistein's ability to induce BDNF in male and female mice. Results: Our in vitro data indicate that genistein at 100nM significantly reduces the amount of cell death induced by glutamate in cortical explants which express both ERɑ and ERβ. Our in vivo data indicate that age does affect ER expression but it does so in a sex and brain region specific manner. Genistein's effect on BDNF levels were also age, sex, and brain region specific. Conclusions: Our results indicate that genistein can be protective, but its protective effects may be dependent on the expression of appropriate ERs and their capacity to influence BDNF signaling.
PYRUVATE DIMERIZATION BY DIVALENT METAL CATIONS
(2013-04-12) Barnes, David
Purpose: Pyruvate enriched cardioplegia has been shown to reduce cardiopulmonary bypass induced inflammation and oxidative stress. Cardioplegia solutions are stored in the hospital pharmacy at room temperature. It has been argued that pyruvate is unstable in aqueous solutions containing divalent metal cations and undergoes an aldol condensation reaction to form parapyruvate. This substance is a potential inhibitor of a critical step in the TCA cycle, oxoglutarate dehydrogenase, and therefore may be toxic. Our pilot study is testing whether pyruvate remains stable in solution in the presence of a metal catalyst. Methods: Aqueous solutions of 5 mM pyruvate were prepared in 0.5 M Tris and aliquoted into test tubes. Zn2+ (ZnCl2) was then added to the test tubes at 0, 0.1, 0.3 and 1.0 mM concentrations. The solution was buffered to pH 4 to prevent precipitation of the Zn2+ which occurred at neutral pH. The solutions were stored in the dark at 20 and 4 ℃ to assess the effect of temperature on the aldol condensation. Absorbance of ultraviolet light (315 nm wavelength) by the pyruvate-Zn solution was measured by spectrophotometry at 0 and 10 days to detect formation of parapyruvate, which absorbs light at that wavelength. Results: The changes in absorbance of the solutions kept at 20 ℃ were as follows: 0 mM Zn2+ -0.002, 0.1 mM Zn2+ 0.007, 0.3 mM Zn2+ -0.011, 1.0 mM Zn2+ -0.0195. The corresponding absorbance changes in the solutions at 0 ℃ for 10 days were as follows: 0 mM Zn2+ -0.009, 0.1 mM Zn2+ 0.0015, 0.3 mM Zn2+ -0.005, 1.0 mM Zn2+ -0.0105. Thus, at both temperatures, only the highest Zn2+ concentration, 1 mM, produced a detectable, albeit modest, change in absorbance at 315 nm, and that change was in the direction opposite that which would indicate pyruvate dimerization. Conclusions: Over the course of 10 days, no appreciable pyruvate dimerization could be detected by spectrophotometry. Thus, pyruvate appeared to be stable in aqueous solution, even over 10 days at 20 ℃. To confirm these results, we are currently measuring pyruvate concentrations at 0, 1, 3, 7 and 14 days by a spectrophotometric assay at 340 nm utilizing the lactate dehydrogenase reaction, in which pyruvate reduction to lactate consumes NADH. This method will enable us to verify that the apparent absence of parapyruvate is accompanied by a stable concentration of pyruvate over time. Future studies will test the impact of other divalent metals, including Mg2+, an important component of many cardioplegia formulations.
ASSESSMENT OF PHYSICAL ACTIVITY AMONG PATIENTS WITH RISK FACTORS FOR METABOLIC SYNDROME IN A RURAL COMMUNITY
(2013-04-12) Peebles, Rebecca
Purpose: Metabolic syndrome (MetS) is a cluster of medical conditions that synergistically increase the risk for development of cardiovascular disease and type two diabetes mellitus. The rapid and persistent rise in the prevalence of MetS has sparked much interest and debate among researchers regarding activity and inactivity physiology. Exercise as a prescription for prevention and management of this disease process has been suggested and explored. The purpose of this study was to address the relationship between physical activity levels and the presence of MetS risk factors within a rural community. Methods: Patients from a family medicine clinic in San Saba County, Texas were recruited, consented, and given a survey to complete. The survey assessed the amount of physical activity levels, presence of MetS risk factors and demographic information of each participant. Results: Frequencies of the five MetS risk factors were calculated revealing 7.7% of participants had none, 33.3% had one, and 20.5% had two. 38.5 % self-reported three or more risk factors which qualified them to have MetS. There was a medium, negative correlation, r = -0.33, n=31, between increase in moderate-to-vigorous intensity physical activity at work and a decrease in the presence of MetS risk factors. However, the relationship was not statistically significant (p=0.067). No correlation was observed between exercise and the presence of MetS risk factors (r = 0.084, n = 17, p = 0.75) or time sitting and the presence of MetS risk factors (r = 0.094, n =28, p =0.063). A one-way, between group analysis of variance showed statistical significance between high school graduates and higher levels of education, but no statistically significant differences between other levels of education or any income groups. Conclusions: Based on the data collected for this project, there is no significant association between exercise and the presence of MetS risk factors. However, over the past two decades, exercise has been well documented to decrease the development of risk factors and slow or even prevent the progression to fulminant disease. The deviation of the results of this investigation from prior research is likely due to the limitations and confounding factors of this study. Further research is needed to make definitive remarks regarding the role of exercise in prevention and management of MetS.
TEXAS DEPARTMENT OF STATE HEALTH SERVICES NUTRITION, PHYSICAL ACTIVITY, AND OBESITY PROGRAM EVALUATION
(2013-04-12) Cardarelli, Kathryn
Purpose: The purpose of this project is to develop an implementation and evaluation plan for the "Strategic Plan for Obesity Prevention in Texas, 2012-2021." This includes an assessment of current partnerships between the Texas Department of State Health Services (DSHS) and organizations, coalitions, and community groups involved in obesity prevention in Texas. Methods: A database of current stakeholders by public health region and stakeholder type will be created and new partners will be sought out based on gaps in representation. An online survey will be administered, assessing obesity prevention strategic areas of focus among partners, prior partnership with the DSHS, and types of obesity prevention activities organizations would be willing to partner on with DSHS. Results: A database with 527 potential partners representing 218 organizations involved in obesity prevention in Texas has been compiled. A survey instrument has been developed and is in the process of being pilot tested. Conclusions: The development of an implementation and evaluation plan for obesity prevention efforts in Texas will lead to modification and improvement of DSHS activities related to obesity prevention and lead to the establishment of new partnerships and collaborative work to reduce the prevalence of obesity and associated chronic diseases in Texas.
TESTICULAR TORSION IN A NEONATE
(2013-04-12) Gowani, Faaria
Purpose: This poster will present a rare case of a congenital testicular teratoma in a 4 week old male who presented to Cook Children's Emergency Department with a testicular torsion. We will discuss the imaging studies of choice and management when investigating scrotal masses and testicular swelling. Methods: Retrospective review of one patient's medical records, including imaging studies and pathology results, from date of admission to discharge as well as a review of pertinent literature. A transcrotal surgical approach was used rather than an inguinal approach because the primary concern was torsion at the time. During the operation, the surgeon noted the testicle to be grossly torsed, uniformly gray and hardened. The appearance was consistent with a tumor and so the testicle was resected and sent for pathology. Results: In respect to diagnosis of testicular masses, literature favors radiologic imaging like CT scan. When testicular torsion is suspected, however, the imaging studies of choice are ultrasound with Doppler. Conclusions: The appropriate use of imaging modalities is pivotal when approaching testicular changes in the perinatal period. When Doppler ultrasound suggests ischemic damage is eminent, it is imperative to prioritize saving a testicle over obtaining an exact diagnosis of the cause. Neonatal teratomas are rare, for the most part clinically benign and usually diagnosed at birth. In this case, however, the teratoma presented as a testicular torsion which required emergent surgery before a sure diagnosis of the cause could be made. Further studies need to be done to determine the best approach to testicular torsions in the neonatal period.
INVOLVEMENT OF ESTROGEN RECEPTOR BETA 5 IN THE PROGRESSION OF GLIOMA
(2013-04-12) Li, Wenjun
Purpose: Emerging evidence suggests a decline of ERβ expression in various peripheral cancers and ERβ has been proposed as a cancer brake that inhibits tumor cell growth and proliferation. Our current study analyzed the expression and function of ERβ in human glioma. Methods: Expression of ERβ isoforms in human glioma was analyzed using western blot, immunohistochemsitry and real-time PCR. ERβ expression regulation was investigated in GBM cell line U87. ERβ isoforms were cloned and stable cells were made to evaluate the effects of ERβ on cell signaling and growth/proliferation of GBM cells. Results: we have identified ERβ5 as the predominant isoform of ERβ in human glioma and its expression was significantly increased in human glioma as compared with non-neoplastic brain tissue. Hypoxia and activation of hypoxia inducible factor (HIF) increased ERβ transcription in U87 cells, suggesting elevated ERβ expression in glioma might be induced by the hypoxic stress in the tumor. Over-expression of either ERβ1 or ERβ5 increased PTEN expression and inhibited activation of the PI3K/AKT/mTOR pathway; ERβ5 also inhibited the MAPK/ERK pathway. In U87 cells, ERβ1 and ERβ5 decreased cell proliferation and decreased cells in the S+G2/M phase. Conclusions: Our findings suggest hypoxia induced ERβ5 expression in glioma as a self-protective mechanism against tumor proliferation and that ERβ5 might serve as a therapeutic target for the treatment of glioma.
ASSESSING TREATMENT ELIGIBILITY AND REARREST STATUS IN STREET SEX WORKERS CONTACTED THROUGH THE DALLAS POLICE DEPARTMENT S PROSTITUTE DIVERSION INITIATIVE
(2013-04-12) Talari, Deepika
Purpose: To assess eligibility for immediate diversion into treatment among prostitutes contacted through the PDI and evaluate recidivism based on their final disposition (jail, residential treatment, released with referral to outpatient treatment) from October 2007 through September 2012. Methods: Eligibility for immediate diversion is defined on the basis of charge classification. Prostitutes committing misdemeanor C offense were eligible for immediate diversion to treatment services. Persons committing prostitution offenses with higher charges (MA, MB, and SJF) were ineligible for immediate diversion, but provided another opportunity to participate in treatment at pre-trial release. Eligibility was determined from the DPD's booking form. Data for follow-up of women diverted to residential treatment was provided by the Nexus Recovery Center. The number of days in jail for PDI participants placed in custody was provided by the Dallas County Pre-Trial Release Division. Results: Eight hundred and sixty sex workers were contacted by the PDI at the end of five years. The majority of sex workers contacted were by arrest (n=807). Fifty-three voluntarily walked onto the street staging site for services. Four hundred and seventy-four contacts were eligible for immediate diversion to treatment. Of those eligible for treatment, 59% opted to enter treatment. Three hundred and eighty-nine participants ineligible for immediate diversion were transported to jail. Of the 177 contacts entering in-patient treatment services, 61 successfully completed the initial treatment program. More than half of the treatment completers were not subsequently rearrested when compared to the contacts that went to jail (35%). Conclusions: Ineligibility for immediate diversion because of higher arrest charge may be a potential barrier to women who want to enter treatment but are not able to do so. Sex workers that went to jail had higher proportion of rearrests compared to those that chose treatment services suggesting that immediate diversion for ineligibles sent to jail may be a worthwhile legislative effort. Further analysis is required to identify key factors which influence recidivism among street sex workers.
POPULATION-BASED RATES AND CORRELATES OF SELF-REPORTED FREQUENT MENTAL DISTRESS IN DIFFERENT SOCIO-GEOGRAPHIC ENVIRONMENTS IN TEXAS
(2013-04-12) Akinboro, Oladimeji
Purpose: Background: Frequent mental distress (FMD) is an indicator of poor mental health used in health-related quality of life surveillance. FMD is defined as reporting at least 14 days of mental ill-health in the prior 30-day period. Objectives: 1. To examine FMD rates in different sociogeographical populations in Texas 2. To evaluate the population-based correlates of FMD 3. To assess the use of medication for mental health problems among individuals with FMD Methods: At least 385 adults each from six counties in Texas (N=2,330), selected using probability-based dual-frame random digit dialing, were surveyed via computer-assisted telephone interviews between September and November 2012. The sampled counties were Hale (rural northwest); Lubbock (urban northwest); McLennan (urban central); Jim Wells (rural south); Willacy (rural south); and Webb (urban south). A forward stepwise procedure (entry criterion: p Results: FMD prevalence ranged from 4.5% (95% CI: 2.35, 6.57) in Lubbock county to 11.1% (95% CI: 5.36, 16.90) in McLennan. Lower odds of FMD were seen in Hispanics (vs.) non-Hispanic whites (OR=0.31, 95% CI: 0.15, 0.62); the elderly (e65 years) vs. 18-44 year-olds (OR=0.34, 95% CI: 0.15, 0.77); and males vs. females (OR=0.50, 95% CI: 0.27, 0.93). Higher odds of FMD were seen with inability to work vs. employed (OR=8.38; 95% CI=4.03, 17.43); and rarely/never having social support vs. most times/always (OR=4.59, 95% CI: 2.22, 9.51). 41.2% (95% CI: 27.40%, 55.00%) of those with FMD were on medication for mental health or emotional problems. Conclusions: FMD rates may vary across sociogeographic environments in Texas. Strengthening the social support systems for those with FMD holds promise for addressing the burden of poor mental health if the nature of association between social support and FMD can be clearly elucidated. A low medication usage rate among those with FMD suggests a need for increased clinical surveillance, and treatment for mental and emotional problems.
EFFECTS OF HYPERBARIC OXYGEN TREATMENT ON IRRITABLE BOWEL DISEASE
(2013-04-12) Shaygan, Lida
Purpose: Irritable bowel diseases (IBD), including Crohn's disease and ulcerative colitis, are idiopathic inflammatory disorders of the gastrointestinal tract that lead to chronically inappropriate immune responses against normal flora in the gut. Among other factors, oxidative stress and increased intestinal tissue injury have been indicated in patients with IBD. Hyperbaric oxygen treatment (HBOT) has been successfully used in humans to treat different conditions such as decompression sickness in scuba diving (Gill et al., 2004), carbon monoxide poisoning, and poor wound healing in diabeteic patients (Tiaka et al., 2011). The purpose of this experiment was to determine the effect of hyperbaric oxygen treatment on colon inflammation in irritable bowel disease. Methods: Colitis was induced in mice using dextran sodium sulfate (DSS), according to a previous described model (Wirtz et al., 2007), and one of the groups was treated with hyperbaric oxygen. 24 eight-week old male C57-BL/6 mice (Jackson Laboratories) were divided into 3 groups: a control group, which was only given distilled water; a second group in which IBD was induced through a 14 day DSS (3%) in drinking water, and a third group also induced with a 14 day DSS (3%) in drinking water and simultaneously treated with HBO daily for two hours. Daily weight loss for all mice was recorded, colons were measured, and colon tissue was histologically analyzed. Results: Hyperbaric oxygen treatment of DSS induced mice led to a significant (P <.05) increase in body weight and colon weight/length ratio measurements compared to DSS induced mice that did not undergo hyperbaric oxygen treatment. Conclusions: Hyperbaric oxygen treatment (HBOT) of colitis induced mice does not appear to decrease colon weight/length ratio, a reliable marker of inflammatory responses in IBD (Galvez et al., 2000). However, HBOT does improve survival and maintains body weight at better levels than DSS-induced mice without treatment. Histological analysis of colon tissues is pending and will provide a better indication of the degree of inflammation in DSS induced mice treated with HBOT.

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