2016
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Item A Cadaveric Study of Anatomical Variations in Neurovascular Branching Patterns of the Head and Neck(2016-03-23) Wehring, Spencer; Kirchhoff, Claire PhD; Hyder, KamilahAt approximately the level of the fourth cervical vertebra (C4), the common carotid artery (CCA) bifurcates into the internal carotid artery (ICA) and the external carotid artery (ECA) to supply the brain and facial structures, respectively. The purpose of this study is to examine anatomical variations in the origin and order of the left and right sides of the ascending pharyngeal artery, lingual artery, and thyrocervical trunk, which branch off the ECA, as well as the location of the vagus nerve within the carotid sheath with respect to neighboring vessels. Possible differences between left and right sides as well as males and females for these vessels were examined. This study includes data from cadavers (n = 63) made available through the University of North Texas Health Science Center (UNTHSC) Willed Body Program. Variations were documented through responses to a data sheet with multiple-choice questions; side and sex differences were evaluated using chi-square tests in SPSS. Significant differences between left and right sides for all vessel branching patterns were detected (X2 ≥ 25.9, df = 1, p ≤ 0). In addition, differences were found between males and females in the left ascending pharyngeal artery (X2 = 9.8, df = 1, p = 0.022), right thyrocervical trunk (X2 = 14.483, df = 1, p = 0.017), and left vagus nerve (X2 = 26.773, df = 1, p = 0.007). From this study it may be concluded that significant branching variations of the ECA exist. This information opens up questions such as whether or not there are evolutionary advantages to specific anatomical variations such as if certain branching patterns provide better blood flow to specific regions, or if there are physiological advantages associated with different locations of the vagus nerve. From a surgical standpoint, further study of anatomical variations can provide better insight as to whether there are complications that can be associated with particular branching patterns, or if certain vessels are more susceptible to damage from spontaneous vascular injury (e.g., stroke, aneurysm).Item A Comparison of Three Screening Tests in Detecting the Prevalence of Latent Tuberculosis Infection in Refugees by History of Residence in Refugee Camps(2016-03-23) Board, Amy; Carlson, Erin; Kolasani, BalajiPurpose: The purpose of this study was to examine residence in a refugee camp as a predictor of testing positive for latent tuberculosis infection (LTBI) according to each of three LTBI screening tests. Methods: Data were obtained from a study funded by the Centers of Disease Control and Prevention (CDC) through the Tuberculosis Epidemiologic Studies Consortium. Refugees presenting at Tarrant County Public Health in Fort Worth, Texas, from countries classified by CDC as having a medium or high risk of tuberculosis (TB) were eligible to participate. Participants were interviewed to obtain data on variables associated with LTBI and received three LTBI screening tests: QuantiFERON-TB Gold In-Tube (QFT), T-SPOT TB, and the tuberculin skin test (TST). The results of each screening test were used as the indicator variable for LTBI. Data analysis was conducted for each screening test result independently using logistic regression to adjust for potential confounders including age, gender, birth country, education, income, smoking, alcohol use, history of incarceration, and being a close contact to a TB case. Results: Of the 994 participants, twenty-six percent originated from medium-risk countries, 22% from high-risk countries in Africa, and 52% from high-risk countries in Asia. The odds of having LTBI for those who lived in a refugee camp compared to those who did not differed according to the screening test used, but was not significant for any of the three tests (QFT OR 0.843, 95% CI 0.568–1.252; T-SPOT OR 0.819, 95% CI 0.548–1.226; and TST OR 1.121, 95% CI 0.791–1.590). Conclusions: Among participants in our study, living in a refugee camp conferred no significantly increased risk of LTBI when adjusted for other predictive variables, independent of the type of screening test utilized.Item A Dynamic Approach to Targeting Acid-Sensing Ion Channels: Computational simulations reveal key residues in ASICs(2016-03-23) Liu, Jin; De La Cruz, DanielThe current molecular dynamics (MD) research project employs virtual model building as a tool in elucidating the functions associated with key calcium binding sites of acid-sensing ion channels (ASICs). These integral membrane proteins, with neuronal proton-sensitive channels associated with pain and central nervous system diseases, represent novel therapeutic targets for these diseases. ASIC1 and ASIC3 are two subtypes of ASICs with highly conserved channel “pore” sequences, but play different roles in the development of hyperalgesia after inflammatory muscle injury. It has been proposed that the removal of calcium continues to allow the ASIC3 channel to open, but this is not the case for ASIC1. The objective of this project is to identify key residues responsible for the distinct gating mechanisms of ASIC1 and ASIC3, utilizing MD simulations. Model building through software, CHARMM-GUI membrane builder program, utilizing the RCSB-PDB (4KNY), has allowed the manipulation and examination of ASIC1’s amino acid sequence. Six simulation trajectories were carried out (accumulative 300 ns- 50 ns per trajectory) through remote access to TACC supercomputer center using NAMD simulation software. Previous experimental work has shown that unlike ASIC3, the ASIC1 channel cannot be opened by the removal of calcium. Despite ASICs' highly conserved channel sequence, this characteristic difference between these two subtypes may be defined by one key residue: a glutamic acid residue found in ASIC3, position 429, versus a glycine residue in ASIC1. Introduction of G429E mutation opens the ASIC1 channel. Consistent with experimental observation, analysis via VMD visualization software revealed the G429E mutant has a wider channel opening than the WT. We further identified that this opening is facilitated by the electrostatic interaction of glutamic acid 429 and asparagine 65 of lateral chains. We identified key residue responsible for the distinct gating mechanisms of ASIC1 and ASIC3. Located at the lipoprotein interface, this key “gating” region of the pore may prove useful in the identification of novel pharmacological targets and understanding the differences in channel gating between ASIC1 and ASIC3. Novel applications are sought for the selective targeting of ASICs channel subtypes, as well as, targeting ASICs within specific regions of the body.Item A fluorescent biosensor for the detection and imaging of a cancer biomarker(2016-03-23) Mummert, Mark; Bora, Ilkay; Shah, Sunil; Gryczynski, Ignacy; Borejdo, Julian; Gryczynski, Zygmunt; Fudala, Rafal; Chib, RahulPurpose: Cancer is among the leading cause of death worldwide with approximately 8.2 million deaths. Cancer mortality can be reduced if it can be detected and treated at early stages. Certain biomarkers like hyaluronidase are reported in the literature for the screening and detection of cancer. It is an endoglycosidase that degrades hyaluronic acid (HA) and this enzyme is overexpressed in various cancers. Therefore, it is of great interest to develop a simple, sensitive and fast technique with which one can estimate the activity/level of hyaluronidase. We have developed a fluorescent biosensor for the detection of hyaluronidase activity/level. This probe was developed by labeling hyaluronic acid with a long lifetime fluorophore. Monitoring the cleavage of hyaluronic acid by measuring the changes in the fluorescent properties of the biosensor will be a simple and precise tool reflecting hyaluronidase activity and can be used for the detection of cancer. Methods: This fluorescent biosensor was developed by heavy labeling of hyaluronic acid with an orange/red emitting azadioxatriangulenium (ADOTA) fluorophore. ADOTA in water emits at 560 nm with a long fluorescence lifetime of ~ 20 ns. The hyaluronidase activity was measured as a function of the change in the steady-state fluorescence intensity and fluorescence lifetime of the biosensor. Fluorescence lifetime imaging microscopy (FLIM) was also used to image hyaluronidase activity in cancer cells. Results: The heavily ADOTA labeled hyaluronic acid (HA-ADOTA) has a red shift in the peak emission wavelength (605 nm), a weak fluorescence signal and a short fluorescence lifetime due to efficient self-quenching. In the presence of enzyme hyaluronidase, the brightness and fluorescence lifetime of the sample increases with a shift in the peak emission to its original wavelength at 560 nm. The ratio of the fluorescence intensity of the HA - ADOTA probe at 560 nm and 605 nm can be used as the sensing signal for detecting hyaluronidase. Recovery in the fluorescence lifetime was used for fluorescence lifetime-based imaging of cancer. Conclusions: Our results show the ability of this the HA-ADOTA probe to detect activity/level of hyaluronidase in biological samples. Due to long fluorescence lifetime of the dye, it can be also be used to remove the background in cellular images. In future, this novel technology can be used to design a small device which can be used in primary care settings for the screening of cancer.Item A new technology platform for combating Zika and other mosquito-borne infectious diseases.(2016-03-23) Schetz, John PhD; Dalwadi, DhwanilPurpose: Mosquitoes are a growing global concern and can transmit infectious diseases such as Zika, West Nile, Dengue, and Chikungunya viruses. Though programs to reduce mosquito populations are helpful, personal outdoor protective measures such as topically applied repellants are the best way to prevent disease transmission. The octopamine receptor (OctR) is a G protein-coupled receptor exclusive to invertebrates making it an attractive target for developing novel arthropod deterrents for use in vertebrates (e.g., humans, pets, livestock). The goal of this project is to develop and validate a high throughput assay that will facilitate the discovery of novel OctR ligands that act as arthropod deterrents. Materials and methods: A cell line stably expressing a cloned arthropod OctR was created as an in vitro model for high throughput evaluation of novel OctR ligands. A barnacle OctR was utilized as a proxy because the cloned mosquito OctR was not available at the time these studies were initiated. The functional activity of the OctR ligands was quantified using a fluorescent calcium sensitive probe to detect Gq-mediated changes in intracellular calcium. In order to complement the molecular assessment of our OctR ligands, a further evaluation was conducted in whole organisms by quantifying barnacle cyprid hyperactivity behavior. Results: Several potent and novel OctR agonists were discovered by measuring activation of a Gq-coupled arthropod OctR. These same compounds induced a hyperactivity response in cyprids. In both cases, their effects could be reversed by an OctR antagonist. These ligands were subsequently found to also protect against biting by two different species of disease-carrying mosquitos, including the Texas-inhabiting species that carries the Zika virus. The inference is that the cloned barnacle OctR serves as a reasonable tool for predicting the arthropod activity of OctR ligands. Conclusion: A high throughput assay was developed that enabled evaluation of the OctR as a target receptor for arthropod deterrents. Using this platform several OctR agonists were discovered whose in vivo properties are consistent with deterency behaviors in different arthropod species: loss of fine motor control as measured by hyperactivity responses in cyprids and prevention of biting in mosquitos. Potential future applications for this technology might include topically applied mosquito deterrents, as well as additives for marine antifouling coatings.Item A Novel Multiplex Assay for an Ancestry-Informative Marker (AIM) Panel of INDELs(2016-03-23) Sage, Kelly; LaRue, Bobby; King, Jonathan; Sturm, SarahThe current standard for forensic laboratories in criminal casework is to use Short Tandem Repeat (STR) markers to develop an evidentiary profile to compare with a reference profile. Commercially available STR amplification kits yield amplicons 100 to 500 base pairs (bp) in length. A common problem encountered by scientists is degraded DNA samples that are only 180-200 bps in length. These samples fail to amplify some loci and therefore produce an incomplete STR profile. STRs are used for identity testing because of their high discrimination power. However, there are cases where no STR match was obtained through a DNA database search and thus no investigative lead is obtained. The bioancestry of the donor of the sample could aid law enforcement in such cases. Another class of markers that could provide investigative value from degraded DNA samples is Ancestry-Informative Marker (AIM) Insertion/Deletions (INDELs). INDELs are polymorphisms that can be amplified from degraded samples due to their smaller amplicon size. AIMs have the ability provide bioancestry information. This project used a previously developed panel of AIM-INDEL markers to develop a multiplex PCR-based assay specifically for these identity-testing applications.Item A qualitative analysis on the discharge process of high-risk infants from the NICU(2016-03-23) Johnson, Yvette MD MPH; Lamping, AshleyPurpose: Poor discharge planning from the NICU may lead to negative outcomes in high-risk infants. Proper caregiver education may decrease the chance of post-NICU readmission and/or adverse health outcomes. There is a lack of follow up studies in the literature. This pilot study was designed to identify any issues that may exist in the current discharge process at CCMC. The results can be used to reevaluate and/or change the planning process for the benefit of future NICU patients and their families. Materials and Methods: Two assessments were distributed on two different occasions between two sample populations. The assessments were distributed within two weeks prior to discharge from the CCMC NICU and on the first follow up visit in the NEST clinic. 22 parents/guardians were interviewed. A higher score on either survey indicates a better quality of life. Results: Prior to discharge, the parents/guardians of NICU patients averaged a 96.2% score in family cohesion, 97% in infant well being, 85.9% in maternal well-being, 89% in maternal comfort, 52% in time impact, and a 79.2% score in family cohesion. On the first follow up visit, parents/guardians averaged a 80% score in parent quality of life, 65.45% in infant progress, 75.9% in overall quality of life, 84.1% in transition to home, 93.5% in NICU experience, 84.8% in maternal confidence, 43.9% in coping and adjustment, and 73.5% in maternal comfort. Conclusions: Overall, families feel adequately prepared for the discharge process and the transition from the NICU to home. Results from this pilot study indicate a need for more maternal counseling and parent education pertaining to each child’s development and growth. Coping and adjustment is the parameter that scored lowest overall. A follow up study with a larger sample size is needed to further identify factors that could be improved in the discharge planning process.Item A STEP in the Right Direction: An Interdisciplinary Approach to Transitional Care (2016)(2016-03-23) Allen, John G.Purpose: The Affordable Care Act, calls for more focus on finding innovative delivery systems that improve care, increase efficiency, and reduce costs. Background: Hospital readmissions, excessive falls, and poor quality of life are factors that unnecessarily increase healthcare costs. The Safe Transitions for the Elderly Patients (STEP) program is a hybrid transitional care model developed by the UNT Health Science Center (UNTHSC) as part of an 1115 Waiver to address these factors in a home care setting in Tarrant County. Objectives: The primary goals of STEP are to reduce all-cause 30 day hospital readmissions, improve quality of life, and decrease falls among Medicaid patients over 50 years through a collaborative and interdisciplinary approach to patient care. Methods: An interprofessional team that includes a physician/geriatrician, nurse practitioner, physician assistant, social workers, physical therapists and a dietician assess and treats the pateint in the home for up to 90 days post hospital discharge based on the individual patient needs. Conclusions: Through this model, UNT Health Science Center has the opportunity to demonstrate a unique transitional care model that will improve health care delivery post-hospitalization.Item A Vital role for Median Preoptic AT1a Receptors in the Sustained Hypertension of Chronic Intermittent Hypoxia(2016-03-23) Cunningham, J. Thomas; Shell, BrentPurpose The hypoxemia from Sleep Apnea (SA) results in hypertension during both the hypoxic sleeping period and the normoxic waking period. This pathophysiological sustained hypertension persists during waking hours and is a source of numerous cardiovascular sequlae. In order to better understand the neurological changes that underlie this disease state, our lab utilizes Chronic Intermittent Hypoxia (CIH) to model the hypoxemia and generate the hypertension of SA sufferers. Previously, our lab has shown that the Median Preoptic Nucleus increases in both neuronal activity and Angiotensin Type 1a Receptor (AT1aR) RNA expression in response to CIH. The MnPO is situated in a critical location that allows it to receive inputs from nuclei outside of the blood brain barrier and provide inputs to regions that control sympathetic outflow, and therefore blood pressure. The ability to modulate sympathetics based upon peripheral inputs coupled with increased activity and AT1aR expression leads us to hypothesize that increased Angiotensin signaling to the MnPO is essential for the sustained component of hypertension from CIH. Methods Male Sprague-Dawley rats were microinjected in the MnPO with either a virus to knockdown AT1aR expression (shAT1a) or a scramble virus (SCR) and instrumented with radio telemetry a week later. Radio telemetry provides continuous recording of cardiovascular variables. After a week of surgery recovery the animals were monitored for a 5 day baseline period before experiencing 7 days of CIH. The morning of the final day, the animals were either perfused with formaldehyde for immunohistochemistry (IHC) or their brains were snap frozen for quantitative PCR. Results Rodents injected in the MnPO with the shAT1a did not exhibit the sustained component of hypertension compared to SCR animals (P Conclusions Overall, this data indicates that the increase in AT1aR expression in the MnPO is essential for the development of the sustained component of CIH hypertension. The shAT1a virus successfully prevents the increase in AT1aR expression and this leads to normal waking blood pressure in the CIH exposed rodents. IHC results indicate that there is less activity in the MnPO and RVLM of the rodents most likely related to reduced sympathetic outflow. This data lends support to optimizing our current treatment regiment through blood brain barrier AT1aR blockers and ACE inhibitors. Future treatment methods could focus solely on preventing Angiotensin as a peptide neurotransmitter in the MnPO to ameliorate neurogenic hypertension.Item Accentuated Antagonism in Cold Induced Sympathetic Activation(2016-03-23) Jouett, Noah; Sanchez, Amani; Miller, Richard; Lawrence, Julie; Smith, Michael PhD; Thomas, Sibi; McDaniel, CharlesTitle: Accentuated Antagonism in Cold Induced Sympathetic Activation Introduction: Accentuated antagonism (AA) is a physiological phenomenon where sympathetic nerve activity (SNA) potentiates the action of the vagus nerve on heart rate slowing. This concept has been thoroughly investigated in animals but has not sufficiently been studied in humans. Exploring AA has significant public health relevance because in states when SNA is high, any given activation of the vagus may slow heart rate to a dangerous degree. Therefore, giving cardio-selective sympathetic blocking agents may have significant clinical utility in these settings. Hence, we hypothesize that R-R interval (RRI) will be higher when background SNA is high during 4 degree Celsius cold pressor test (CPT) compared to a room temperature control, and that this difference will be mitigated by giving intravenous metoprolol. Methods 4 healthy human subjects were recruited and informed consent was obtained according to the Declaration of Helsinki. Subjects first underwent baseline -60 mm Hg neck suctions to stimulate vagal nerve-mediated heart rate slowing through the baroreflex. These suctions were repeated after submersion of the hand at wrist level in 4°C water and then 23°C water. These conditions were repeated with infusion of 10 mL saline placebo and up to 10 mg of intravenous metoprolol. We were able to differentiate between the vagal and sympathetic effects on the heart by either infusing saline or blocking the SNA with metoprolol at both temperatures. Results: In comparison of the placebo group with the Metoprolol group in 25°C water, we did not see a significant different in the RR interval (Difference of Means=58.007 milliseconds; P=0.344). In addition we did not see a statistical difference when comparing the RR interval of the placebo group with the Metoprolol group in 4°C water (Difference of Means=72.073 milliseconds; P=0.247). However, there are significant trends within the data that deserve further study. Conclusions: We believe the lack in statistical significance of the data presented is due to the small number of participants in the study. This study warrants further elucidation of the concept of accentuated antagonism in human subjects.Item Activation of a putative membrane androgen receptor increases the efficacy of the chemotherapeutic agent, temozolomide, in a human glioblastoma cell line(2016-03-23) Badeaux-McGilvray, Adrienne; Singh, Meharvan PhD; Brock, CourtneyGlioblastoma Multiforme (GBM) is a form of brain cancer with very poor prognosis such that the life expectancy of a person with this disease is about one year after diagnosis. Moreover, current treatment regimens are only able to extend the life span by mere months. Based on recent studies from our lab that identified a putative membrane androgen receptor (mAR), which when activated is capable of promoting cell death, we investigated whether exploitation of this receptor could increase the efficacy of current chemotherapeutic agents to combat this deadly and invariably lethal cancer. Using the human glioblastoma cell lines, A172 and T98G, our studies have shown that activation of the mAR (using testosterone or dihydrotestosterone conjugated to bovine serum albumin) not only sensitized the glioblastoma cells to temozolomide (TMZ), the current standard chemotherapeutic agent for GBM, but also suppressed the phosphorylation of Akt, a known survival-promoting factor. Further, in T98G cells that express high levels of O6-methylguanine DNA methyltransferase (MGMT), a DNA repair protein, activation of the mAR suppressed the expression of MGMT. Our data also suggest that these mechanisms may not be mutually exclusive such that inhibition of Akt phosphorylation in and of itself led to a reduction in MGMT expression. Collectively, our data support the targeting of a putative membrane androgen receptor as complementary treatment for glioblastoma.Item Adverse Outcomes from vaginal delivery during immersion in water versus traditional vaginal delivery(2016-03-23) Combs, Shanna; Felini, Martha; Donaldson, Kathleen; Lopez, Tania; Hicks, Candis; Griffith, Lindsay; Cochrane, Cindy; Zimmerman, Leah; Shillington, AmelleHypothesis: There are no adverse events examining four years of hospital midwifery vaginal delivery during immersion in water versus traditional vaginal delivery. At our institution, our Certified Nurse Midwife practice has been practicing vaginaldeliveries via immersion in water since 2008. In light of the ACOG committee opinion 594, we conducted a matched-pair analysis to compare the frequency of adverse events during immersion in water vs traditional vaginal delivery. Materials and Methods: A retrospective chart review was conducted for deliveries occurring at a single urban hospital from 2010 – 2014. Deliveries were grouped into waterbirths and landbirths. Women who had a waterbirth were matched by parity and gestational age to women having a traditional vaginal delivery. Adverse outcomes assessed included lacerations, episiotomy, hemorrhage, APGAR score, shoulder dystocia, and NICU admission. Conditional logistic regression was used to estimate adjusted odds ratios (AOR) and 95% confidence intervals (95% CI). Results: Of the 149 matched pairs assessed, the median age was 28; 71% were Caucasian and 20% were Hispanic. Women were similar across delivery groups in age, race, chronic conditions, and number of previous preterm births. The odds of a laceration during waterbirth delivery were observed to be 90% lower when compared with landbirth (AOR = 0.10, 95% CI: 0.01 – 0.78). Likewise, a poor 1 minute APGAR ( Conclusion: This study suggests that there were fewer lacerations and higher 1-minute APGAR scores among waterbirth deliveries.Item Alcohol and HIV-1 differentially regulate Toll Like Receptor (TLRs) expression and signaling in Primary Human Astrocytes(2016-03-23) Ghorpade, Anuja PhD; Pandey, RichaAbout 69% of human immunodeficiency virus-1 (HIV-1)-positive individuals exhibit some form of HIV-associated neurocognitive disorders (HAND). Several studies have reported that HIV-1 virions, viral proteins and alcohol, individually have direct or indirect effects on HAND pathophysiology. Recently, we showed that alcohol activates astrocytes and regulates inflammation via cPLA2 in HAND. Toll-like receptors (TLRs) are a family of innate immune system receptors that respond to pathogen-derived and tissue damage-related ligands. TLR signaling in immune cells, astrocytes, microglia and neurons may play roles in the pathogenesis of multiple diseases. TLRs are a “missing” link in alcohol-mediated astrocytic response in context of HAND since TLR stimulation by alcohol in glial cells induces secretion of pro-inflammatory molecules. Thus, we explored the role of TLRs in alcohol-induced inflammation and cytotoxicity in primary human astrocytes with HAND. TLRs signaling gene array was performed to screen altered profiles for all 10 TLR family members and 74 downstream signaling molecules. Ingenuity pathway analysis (IPA) was performed to identify potential signaling nodes. Data suggested that HIV-1 and/or EtOH led to differential TLRs expression in astrocytes. We confirmed all 10 TLRs by real-time PCR in four independent astrocyte donors. Alcohol alone and with HIV-1, significantly upregulated TLR1, 2, 3, 4, 5 and 9 as compared to controls and HIV-1 alone. We propose that TLRs regulation plays an important role in astrocytes inflammation upon HIV-1 and EtOH exposure.Item Alteration of Inflammatory Profile following Activation of a Neuroimmune Pathway(2016-03-23) Mathis, Keisa W.; Fairley, Amber; Patel, MaitrybenAbstract Hypertension is estimated to cause 7.5 million deaths worldwide and is a major risk factor for stroke, renal failure, and heart failure, all of which may be potentially fatal. Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disorder with a high prevalence of hypertension. Inflammatory cytokines have been shown to promote the development of hypertension in recent studies. Other studies suggest that acute stimulation of an innate, vagally-mediated, neuro-immune pathway (the cholinergic anti-inflammatory pathway) suppresses the production of inflammatory mediators in the spleen. It is unknown whether chronic stimulation of this pathway is capable of reducing inflammation, and ultimately blood pressure during SLE. Purpose (a): The purpose of this study was to evaluate the effectiveness of stimulation of the cholinergic anti-inflammatory pathway on reducing inflammation in SLE. We hypothesized that pharmacological stimulation of the vagus nerve with CNI-1493 would suppress splenic cytokine release, thereby reducing systemic inflammation. Methods (b): CNI-1493 (8 mg/kg/2swk, IP) or vehicle (saline) was administered twice a week for 4 weeks, starting at 30 weeks of age in female SLE (NZBWF1) and control mice (NZW). At 34 weeks, animals were euthanized and tissues were collected in order to examine splenic and renal inflammation. The spleen and kidney were homogenized using RIPA buffer and the cytokine TNF-a was evaluated using Western blot in these tissues. Results (c): TNF-a expression (normalized to b-actin) was increased in the spleen (36.9±8.7 vs. 22.5±2.8; p=0.02) and renal cortex (8.4±0.4 vs. 3.7±0.5; p=0.03) of SLE mice compared to controls. CNI-1493 had no significant effect on spleen TNF (35.9±4.3), however exacerbated renal cortical TNF (12.5±2.2) in SLE mice. Conclusions (d): Although the results did not support our hypothesis, the data are preliminary and we suspect additional studies are needed to determine the ability of pharmacological stimulation of the vagus nerve to reduce inflammation in SLE mice. Such therapy could potentially benefit hypertensive SLE patients, since chronic inflammation has recently been linked to the development of the disease.Item An evaluation of the RapidHIT® ID system for field forward applications(2016-03-23) Sage, Kelly; Budowle, Bruce; LaRue, Bobby; Wiley, RachelThe utilization of a new Rapid DNA (RDNA) platform to generate CODIS uploadable DNA profiles will serve to be instrumental in improving current DNA typing techniques and in reducing the backlog of forensic reference samples. The RapidHIT® ID (IntegenX; Pleasanton, CA) system is a second generation system in RDNA that has the potential to yield comparable DNA profiles to those achieved by traditional bench methods. The RapidHIT® ID platform is a self-contained, fully-automated, sample-to-profile system with a novel construction designed to reduce it’s footprint as well as the number of samples necessary to be run at a single time, making it condusive to both laboratory and field work application. The RapidHIT® ID system has the capacity to perform direct amplification, electrophoresis, and data analysis in approximately 90 minutes with nominal “hands-on” assistance required. Reliable DNA STR profiles have been generated from reference buccal swabs. The RapidHIT® ID platform was evaluated for concordance, reproducibility, and lack of contamination. Sensitivity and interpretation thresholds were established, and although the system was designed for reference buccal swabs, additional studies evaluating the effects of sample age, inhibitors, and sample collection methods were performed. This new instrumentation provided DNA STR profiles comparable to those obtained from traditionalDNA genotyping methodologies, in addition to complete or partial profiles from the sensitivity studies. Based on preliminary studies, the RapidHIT® ID system is a new RDNA platform that is robust and reliable for generating STR profiles from forensic reference samples.Item Analysis of Comorbid Depression and Diabetes among Males 30 – 50 Years of Age(2016-03-23) Hartos, Jessica; Cheremateng, YaaIntroduction: Depression and diabetes are among the most prevalent chronic diseases in the United States and are common comorbid conditions. The purpose of this study was to assess whether diabetes is a risk factor for depression in a representative sample of males ages 30-50. Methods: This cross sectional analysis used 2013 data from the Behavioral Risk Factor Surveillance System for Mississippi males ages 30-50, N=712. Chi-square analyses and multiple linear regression were used to determine the association between diabetes and depression. Results: Significant relations between diabetes and depression were observed at the bivariate level (p=.02, 95% CI= 1.06, 4.23); however, the relationship was insignificant after controlling for number of chronic health problems, physical activity level, weight, tobacco use, alcohol use, educational level, marital status, age, and ethnicity/race. The relations between number of chronic health problems and depression were significant at the multivariate level. Conclusions: Overall, depression and diabetes were not related in this age group. However, number of chronic health problems was significant for this age group, and thus having multiple comorbidities such as diabetes seems to be a key factor impacting depression risk for males 30-50. Consequently, clinicians should be cognizant of the relationship between comorbidities and depression and provide screening to patients with multiple comorbidities in addition to resources or referrals as necessary.Item Analysis of expression of immune receptors in pediatric acute lymphoblastic leukemia (ALL)(2016-03-23) Mathew, Stephen O.; Mathew, Porunelloor A.; Bowman, Paul; Powers, SheilaAcute Lymphoblastic leukemia (ALL) is the most common type of cancer in children. It is characterized by overgrowth of the lymphocyte precursor (either B cell or T cell) that is nonfunctioning, and crowds out other immune cells. Current treatment options have a success rate of 80-90%. However, those who relapse have a survival rate of only around 25-40%. Also, side effects of current chemotherapy and radiation treatments have been shown to impact the normal growth and development of children. Research has shown that ALL of the B cell lineage is particularly resistant to killing by Natural Killer (NK) cells. NK cells are part of the innate immune system and specialize in killing tumor and virally infected cells. NK cell activation is dependent on a balance of inhibitory and activating receptors and their ligands expressed on the target cell. Our laboratory has previously cloned three immune receptors, 2B4, CS1 and LLT1, which have been shown to play a role in cancer, however their significance and role in childhood ALL have not been evaluated. In this study, we evaluated the expression of immune receptors 2B4, CS1, LLT1, NKp30 and NKp46 in pediatric ALL subjects both male and female in the age range of 3 – 18 yrs. ALL subjects and healthy subjects were enrolled at Cook Children’s Hospital and UNT Health Science Center, Fort Worth, TX with informed consent/assent according to IRB approval (UNTHSC IRB# 2008-094 & CCMC IRB# 2008-57). The blood samples were collected and peripheral blood mononuclear cells (PBMC) were isolated and analyzed by flow cytometry and real-time qPCR for expression of immune receptors. ALL subjects showed altered expression of immune receptors in the PBMC as compared to healthy subjects. There was an overall decrease in the expression of 2B4, CS1, LLT1 and NKp46 in the B lymphoblasts of ALL subjects as compared to healthy subjects. Expression and functional analysis of these receptors in a larger sample size will provide valuable insights to conduct future mechanistic studies to investigate the role of these immune receptors in ALL resistance and relapse. Funded by Cancer Research Foundation of North Texas (CRFNT).Item Analyzing the Association between Adverse Childhood Experiences and an Increase in Body Mass Index among Adolescents (10-17 years)(2016-03-23) Sekhon, Vishaldeep; Chikani, Shalinkumar; Hilliard, Bethany; Hirpara, KomalPurpose: Adolescent obesity is a major public health concern in the United States1, 2. According to the CDC, more than 33% of children and adolescents are either overweight or obese1 . A major known risk factor for changes in BMI status is stress3 . Multiple risk factors, such as living in a food desert, race, and exposure to family and neighborhood stressors cause various emotional and physiological changes in the body, which can increase the risk of adolescent obesity3, 4, 5. Due to this, we use the socio-ecological model to understand intertwined risk factors of adolescent obesity3 . Based on biological and scientific evidence we hypothesized that adverse childhood experiences (ACEs) are associated with body mass index (BMI) status among adolescents aged 10-17 years. Methods: The secondary data analysis was done using the 2011-2012 National Survey of Children’s Health and conducted univariate, bivariate, and polytomous logistic regression to assess the relationship between ACEs and BMI while controlling for gender, federal poverty level, health insurance status, learning disabilities, and how often the studied family eats meals together. The estimation of adjusted odds ratio represents an adolescent having undergone at least one or more ACEs and its effect on BMI measured in three categories: underweight\normal weight, overweight and obese. Results: The odds of being overweight are 1.10 times higher (95% CI 0.94-1.30) for adolescents who are exposed to 1 ACE, while the odds of being overweight are 1.26 times higher (95% CI 1.08-1.47) for adolescents with 2 or more ACEs, with both odds ratios being compared to adolescents with normal BMI and no ACEs. The odds of being obese are 1.13 times higher (95% CI 0.96-1.33) for adolescents who are exposed to 1 ACE, while the odds of being obese are 1.43 times higher (95% CI 1.20-1.71) for adolescents with 2 or more ACEs, with both odds ratios being compared to adolescents with normal BMI and no ACEs. Conclusion: The study observed that increasing the number of ACEs adolescent experiences increases the odds of being overweight or obese. These results indicate that public health professionals should intervene at each level of the socio-ecological model in order prevent major fluctuations in adolescent BMI status.Item Androgen Receptor-Independent Mechanisms for Dihydrotestosterone (DHT)-induced Protection in the C6 Glioma Model of Astrocytes(2016-03-23) Rybalchenko, Nataliya; Singh, Meharvan PhD; Kubelka, NicholasTestosterone and dihydrotestosterone (DHT) exert protection through the activation of the intracellular androgen receptor (AR). However, studies suggest DHT may also exert protective effects by way of alternate mechanisms, including through prior conversion to 3beta-diol, a metabolite that can bind and activate estrogen receptors. Using the AR-deficient C6 glioma, a model of astrocytes, we found DHT was protective against iodoacetic acid (IAA) toxicity. The protective effects of DHT, as assessed by the Calcein-AM viability assay (which is a surrogate measure of cell number), were blocked by the co-application of the non-selective estrogen receptor antagonist, ICI-182,780. Using a complementary viability assay, the MTT assay, which is a surrogate for mitochondrial respiration/activity, we reproduced DHT protection and extended our results to find that 3beta-diol was also protective against IAA-induced reduction in mitochondrial activity. Interestingly, while the effects of 3beta-diol, the presumptive mediator of the effects of DHT, were blocked by ICI 182,780, they were not blocked by the estrogen receptor isoform-selective antagonists MPP (against ERa) and PHTPP (against ERb). Collectively, these data support our hypothesis that DHT is protective against cytotoxicity in a cell line devoid of the classical/intracellular androgen receptor, and that the metabolite of DHT, 3beta-diol, may be an important mediator of DHT’s effects in the central nervous system. Our results also suggest that the capacity to convert DHT to 3beta-diol may be relevant to the protective influence of androgens and estrogens in the postmenopausal women, a time when estrogen and progesterone levels decline significantly, but androgen levels persist.Item Angiotensin II Linked Free Radical Effects on Muscle Sympathetic Nerve Activity During Exercise(2016-03-23) Morales, Gilbert; Jouett, Noah; Raven, Peter PhD; Rodriguez, MauroBACKGROUND: It has been identified that central nervous system (CNS) production of free radicals (FR) scavenges nitric oxide and increases central sympathetic nerve activity outflow. The increased production of FRs in the CNS is a result of increased electron transport chain flux associated with increased brain metabolism and by activation of the renin-angiotensin system (RAS). The pathophysiological increase in Ang II linked FR production is recognized as a major mechanism involved in neurogenic hypertension. During exercise, there is a physiological increase in Ang II and muscle sympathetic nerve activity (MSNA) in direct relation to increasing exercise intensity. PURPOSE: We tested the hypothesis that the exercise induced increase in Ang II linked FR production and MSNA activity during exercise is located within the brain. METHOD: Six healthy subjects performed three randomly ordered trials of 70° upright back-supported dynamic leg cycling after ingestion of two different lipid soluble Angiotensin converting enzyme inhibitors ((ACEi) Perindopril (PER) - highly lipid soluble; Captopril (CAP) non-lipid soluble)) and/or placebo (PL). Repeated measurements of whole venous blood, MSNA, and mean arterial pressures (MAP) were obtained at rest and during steady-state heavy intensity exercise at heart rates (HR) of 120 bpm (e120). RESULTS: Peripheral venous superoxide concentrations as measured by electron paramagnetic resonance (EPR) were not significantly altered at rest (P≥0.4) and during E120 by the ACE inhibitors (P≥0.07). Likewise, baseline MSNA (PL, 25 ± 1.5 bursts/min; CAP, 21 ± 0.7 bursts/min; PER, 25 ± 0.7 bursts/min) and MAP (PL, 86 ± 2.8 mmHg vs. CAP, 84 ± 2.6 mmHg; PER, 84 ± 0.7 mmHg) were unchanged at rest (P≥0.1; P≥0.8 respectively). However, during E120 central acting PER attenuated the increases in MSNA and MAP, increasing only 15±6% for MAP and 24±8% for MSNA, when compared to PL (26 ± 6% MAP; 57±16% MSNA; PCONCLUSIONS:From these data we conclude that centrally acting PER attenuated the central increase in the exercise induced Ang II linked free radical production resulting in an increased central/peripheral NO activity induced reduction in MSNA during heavy intensity dynamic exercise.