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Item DETERMINATION OF GENETIC FACTORS ASSOCIATED WITH RESPONSE TO OSTEOPATHIC MANIPULATIVE TREATMENT IN INDIVIDUALS WITH CHRONIC LOWER BACK PAIN(2014-03) Richardson, Kayla; Cross, Deanna; Kearns, Cathy; Planz, John; Licciardone, John C.OMT (Osteopathic Manipulative Treatment) is an often overlooked, low risk treatment option for management of (Chronic Lower Back Pain) CLBP. My overarching hypothesis is that genetics contributes to OMT response. The study used 216 samples consisting of 111 individuals who received OMT, and a placebo group of 105 individuals who received a sham treatment. Genetic differences between subjects who benefited from OMT (responders) and those who did not benefit from OMT (non-responders) were compared. We found an association between 3 genes (IL-8, GCH1, and LARGE) and response to OMT in individuals who suffer from CLBP. Purpose (a): OMT (Osteopathic Manipulative Treatment) is an often overlooked, low risk treatment option for management of (Chronic Lower Back Pain) CLBP. Underutilization of OMT is partially due to an undefined mechanism of action for the therapy. Our overarching hypothesis is through analysis of genotypic attributes; it is possible to determine which individuals are more likely to respond to OMT leading to insights into mechanisms of action. The current study investigated potential polymorphisms associated with OMT and pain reduction using data previously collected from a CLBP clinical study, which was part of The OSTEOPATHIC Trials. Methods (b): We performed a candidate gene study using single nucleotide polymorphisms (SNPs) within genes previously associated with pain: Catechol-o-methyltransferase (COMT), beta 2 adrenergic receptor (ADRB2), GTP cyclohydrolase GCH1, Interleukin 1 alpha (IL1A), interleukin 1 beta (IL1B), interleukin 1 receptor antagonist (IL1RN), Interleukin 8 (IL8), and like- glycosyltransferase (LARGE). Genotypes from subjects who benefited from OMT (responders) were compared to subjects who did not benefit from OMT (non-responders) using a chi-square analysis to test for associations. For SNPs that showed significance (α=0.05) an odds ratio (O.R.) was calculated. The study utilized 216 samples consisting of 111 individuals who received OMT, and a placebo group of 105 individuals who received a sham treatment. Results (c): SNPs in IL-8, GCH1, and LARGE showed significance (α=0.05) in the OMT group only: IL-8 SNP rs2227543 (O.R. 2.2824 CT, confidence interval (C.I.) 1.0053-5.1818), LARGE SNP rs240070 (O.R. 2.8546 TA, 1.0508-7.7548), and GCH1 SNP rs998259 (O.R. 0.4016 GA, C.I. 0.1600-1.0080). A SNP by SNP interaction was detected within GCH1 between rs998259 and rs3783641. When the rs998259 genotype is GG, rs3783641 is associated with response to OMT (α=0.05, O.R. 2.9630 TA, C.I. 1.1269-7.7907). Conclusions (d): There is an association between genetics and response to OMT in individuals who suffer from CLBP. Individuals with genotype CT in rs2227543 or TA in rs240070 are more likely to respond to OMT whereas individuals with genotype GA in rs998259 are less likely to respond to OMT. Furthermore, if an individual has genotype GG in rs998259 and TA in rs3783641 they are more likely to respond to OMT. Genes in neuronal, immunological, and muscular pathways affect OMT response.Item HIV AND NUTRITION IN A COMMUNITY SETTING(2014-03) Leber, Julie; DeHaven, MarkPurpose (a): A balanced diet and good nutrition help maintain a strong immune system for resisting disease and contribute to improved quality of life. Weight loss, wasting, and malnutrition are common problems which can contribute to HIV disease progression. With recent advances in effective antiretroviral medications, good nutrition can help those infected with HIV to better process their many medications. Diet (and exercise) may help control other symptoms such as diarrhea, nausea, and fatigue, and other metabolic abnormalities such as high blood sugar, cholesterol, and triglycerides. The purpose of this project was to assess the behaviors, knowledge, and attitudes related to modifiable lifestyle factors for improving health outcomes among residents of an HIV/AIDS living facility in Fort Worth (Samaritan House). This study will provide the baseline for understanding the potential value in making future nutritional interventions within the living facility. Methods (b): The Samaritan House in Fort Worth is dedicated to creating a supportive community providing housing and resources for positive change in the lives of persons living with HIV/AIDS and other special needs. A conglomerate of validated questionnaires was administered to Samaritan House residents in order to assess their knowledge, attitudes, and behaviors with regards to nutrition, physical activity, depression, and smoking. Results (c): Results showed that residents intake patterns did not meet the dietary recommendations with regards to fat, fruits, vegetables, and fiber, and that the majority of residents worry considerably about their health but do not change their eating habits because of it. The majority of residents answered that motivations for healthy behavior were driven by internal rather than external factors. 64% screened positive for depression. 54% were active smokers, but 41% had tried to quit in the past year. With regards to physical activity, 33% of residents had a high level, 33% had a medium level, and 33% had a low level. Conclusions (d): Nutritional and lifestyle renovation are a potential source of improvement at Samaritan House. This results of this study will be used to provide a foundation by which later studies can be conducted that examine the effects of dietary interventions (through education and influence of the charitable donations providing food) on the holistic health of this population, which will serve to improve the quality of life and prevention of disease.Item PHYSICAL FUNCTION IN INDIVIDUALS WITH DIGEORGE SYNDROME(2014-03) Perez, Rebecca; Stroud, Brandi; Liu, Hao (Howe); Altuna, Dianne; Ditthakasem, Kanlaya; Salem, YasserThis preliminary study was conducted to assess physical function in individuals with DiGeorge syndrome, also known as velo-cardio-facial syndrome, as compared to healthy individuals. Assessment of physical function across the lifespan is essential in order to maintain physical abilities, better educate families, and bring a higher quality of life to individuals with this disorder. Purpose (a): DiGeorge syndrome, also known as velo-cardio-facial syndrome (VCFS) or 22q11.2 deletion syndrome, is the most common chromosomal deletion syndrome, with an estimated incidence of approximately 1 in 2,000 to 7,000 live births. Clinical presentation of VCFS is highly variable and has more than 180 distinct clinical manifestations. Previous studies have shown, children with VCFS exhibit gross motor abnormalities and global developmental delay. However, little is known about physical function in individuals with VCFS. This preliminary study compares physical function in individuals with and without the syndrome. Methods (b): This study was conducted on 43 individuals, 24 with VCFS (13 males, 11 females) and 19 healthy individuals (6 males, 13 females). Physical function was tested: Timed Up and Go (TUG) test to measure power and velocity, Sit-to-Stand Test (STS) to measure lower extremity strength, Single Leg Stance (SLS) to measure posture stability, handheld dynamometer to measure grip strength, and the 2-minute walk test (2MWT) to measure endurance and gait velocity. Descriptive statistics and the ANOVA test were used to assess differences in physical function between groups and within the group with the syndrome. Results (c): Significant differences between the group with VCFS and the group with healthy individuals were identified in the TUG (7.40±1.45 vs 6.33±1.04; p < .01); right SLS (12.62±12.81 vs 52.27±34.54; p < .001); left SLS (10.09±9.02 vs 52.60±36.19; p < .001); and the 2MWT (469.08±74.09 vs 580.58±105.07; p < .001), but no difference was identified in STS and grip strength. Additionally, significant differences within the group with the syndrome, based on age difference (20 yrs of age), were identified in the 2-minute walk (p. Conclusions (d): Data from this preliminary study indicate individuals with VCFS present with decreased physical function as compared to healthy individuals. Results suggest early assessment procedures for individuals with this condition should include assessment of physical function, especially mobility function. Continued assessment of physical function across the lifespan is essential in order to maintain physical abilities, better educate families, and bring a higher quality of life to individuals with this disorder.Item GENDER-HETEROGENEOUS WORKING GROUPS PRODUCE HIGHER QUALITY SCIENCE(2014-03) Mehtani, Siya; Campbell, Lesley G.; Dozier, Mary E.; Rinehart, JaniceHere we present the first empirical evidence to support the hypothesis that a gender- heterogeneous problem-solving team generally produced journal articles perceived to be higher quality by peers than a team comprised of highly-performing individuals of the same gender. Given that women can and have made an enormous impact on the study of ecology as a minority population, it is important to understand the conditions that promote their equitable participation. However, it is rare to find replicated conditions under which we can compare the opportunities women receive for leadership, participation in academic discussions, and authorship, and the consequent benefits received due to their participation. Here, we quantified patterns of participation and productivity by women in working groups (WGs) at the National Center for Ecological Analysis & Synthesis (NCEAS) by measuring the relative participation of women as PIs, womens’ inclusion in WGs, and as authors. Using data provided by the NCEAS website, we collected information on 157 WGs that started by 1996 and were finished by December 2008. WGs include 10 to 15 researchers who visit NCEAS for 1 to 2 weeks to focus on the analysis and synthesis of existing ecological data. For each WG, we tabulated data on the number and gender of PIs, participants and authors in WGs, and gathered information on PIs’ publication history, quantifying their impact on ecological literature using h-factor, total number of citations, and average number of citations per paper. Using statistical analyses, we assessed consistent differences in participation among male and female participants, PIs and authors. Although women were historically underrepresented as PIs of WGs, their frequency as PIs at NCEAS Is now comparable to the national frequencies in biology, and they are now equally qualified, in terms of impact on the ecological literature (h-index). While women continue to be underrepresented as WG participants, peer-reviewed publications with gender-heterogeneous authorship teams received 34% more citations than publications produced by gender-uniform authorship teams. Promoting diversity not only promotes representation and fairness but may lead to higher quality science. It is important to understand the conditions that promote women’s impact and equitable participation. By actively funding proposals with female PIs, NCEAS and other institutions can predictably change the participation and productivity of female participants.Item BASELINE SYMPATHETIC ACTIVITY IS ELEVATED IN PATIENTS WITH ATRIAL FIBRILLATION(2014-03) Hanson, Gabriel S.; Cielonko, Luke A.; Smith, Michael L.Atrial fibrillation, or AF, is an abnormal rhythm of the heart that is common in many people, particularly in individuals over 60 years of age. The association of AF with other cardiovascular diseases and the potential relation to sudden cardiac death (or cardiac arrest) is not known. This study investigated the baseline activity of the sympathetic nervous system. The sympathetic nervous system is the primary branch of the nervous system that mediates the response to a stress. The findings of this study strongly suggest that sympathetic nervous system activity is increased in AF which may also increase incidence of progression of other cardiovascular disease states including potentially fatal ventricular dysrhythmias. Purpose (a): Most cardiovascular diseases are associated with high sympathetic nerve activity (SNA), and elevations in SNA are known to increase the progression of many forms of cardiovascular disease. Atrial fibrillation (AF) is a serious cardiac dysrhythmia that afflicts a substantial percentage of the population and is known to result in increased risk of blood clotting. This results in a higher risk for pulmonary emboli and stroke. These complications tend to be associated with a generalized fatigue and reduced exercise capacity due to decreased cardiac output. However, the effect of atrial fibrillation on SNA is unknown, thus the purpose of this study was to determine the effect of AF on baseline SNA independent of other factors. Methods (b): Two studies were performed in patients with AF. First, eight patients with drug-refractory AF were studied before and after completion of an AV nodal ablation to normalize the ventricular rate. Microneurographic recordings of SNA were obtained continuously during and after completion of the procedure. Upon effective AV nodal ablation, the patient was immediately paced with a temporary pacemaker inserted in the ventricular apex via vascular access. Ventricular pacing was conducted at the same rate as the patients ventricular rate during their episodes of AF. Baseline SNA was determined prior to ablation and during ventricular pacing. A comparison of SNA was made between the AF state and during the artificially paced ventricular rate, which as stated above was conducted at the mean of their ventricular rate during AF. Second, nine patients with paroxysmal AF were studied during AF and after cardioversion of AF during sinus rhythm. Microneurographic recordings of SNA were obtained continuously during AF and during sinus rhythm. Statistical comparisons were performed for each study with a paired Student's T test to determine the difference in SNA between conditions with AF and without AF. Results (c): For study 1, mean ventricular rates during AF were 93 + 4 bpm (range= 82-128 bpm) and the post-ablation pacing rates were the same and were maintained at a constant regularity with no inter-beat difference. Baseline SNA decreased significantly from 2836 + 332 units to 2291 + 298 units (p < 0.03). For study 2, mean ventricular rates during AF were 98 + 3 bpm (range= 78-140 bpm) and the post-cardioversion sinus rhythm rates were 77 + 2 bpm (range= 62-91 bpm). The baseline SNA decreased significantly from 3755 + 401 units to 2329 + 339 units (p < 0.01). In each case, the measurement of SNA was based on 100 heartbeats, and thus was independent of the rate. Conclusions (d): These data support the hypothesis that baseline SNA is elevated in atrial fibrillation and appears to be independent of rate. These findings support the hypothesis that AF may also increase the risk of progression of other cardiovascular disease states including potentially fatal ventricular dysrhythmias.Item NOVEL GABAA-RHO1 INTERACTIONS WITH ACID SENSING ION CHANNEL LIGANDS(2014-03) Snell, Heather D.; Gonzales, Eric B.γ- amino butyric acid (GABA) is the major inhibitory neurotransmitter in the vertebrate brain, and targets the ionotropic GABAA receptors. GABAC, or GABAA-rho, is a subclass of GABAA receptors located in the retina. A group of ligands, which possess a guanidine group, have been shown to influence classical GABAA receptors. Many, however, have not yet been tried on the GABAA-rho receptor subclass. Our experiments show that these compounds have contrasting effects on the GABAA-rho1 receptor, which could lead to a novel binding site, and explain many side effects of certain drugs containing the guanidine group. Purpose (a): γ- amino butyric acid (GABA) is the major inhibitory neurotransmitter in the vertebrate brain, and targets the ionotropic GABAA receptors. GABAC, or GABAA-rho, is a subclass of GABAA receptors composed entirely of rho (ρ) subunits and are located on the axonal terminal of retinal bipolar cells, where it not only exhibits a tonic inhibitory current, but also regulates the GABA-A and other GABAA-rho synaptic currents. GABAA-rho exhibits unique properties, such as insensitivity to select antagonists of the heteromeric GABAA receptors. A group of ligands, which possess a guanidine group, have been shown to influence GABAA receptors. These compounds, such as (S)-2-Guanidinopropionic acid and guanidine acetic acid were competitive antagonists for the GABAA-rho1 receptor. Other guanidine compounds that are acid sensing ion channel (ASIC) ligands, might also exhibit unique effects on the GABAA-rho1 receptor.We hypothesize that these ASIC ligands will exhibit unique intrinsic activities on the GABAA-rho1 receptor, which is different from that of the heteromeric GABAA receptor. Methods (b): The human GABAA-rho1 receptors were expressed in HEK-293T cells, and activity was analyzed using whole cell patch-clamp electrophysiology. Results (c): When co-applied with GABA and compared to the GABA concentration profile, one ligand was found to decrease the maximal response, with no change in the GABA EC50,while a different ligand with the same guandine group, shifted the GABA EC50 to lower GABA concentrations. When applied alone, it failed to directly activate GABAA-rho1 receptors. Conclusions (d): These contrasting effects suggest that these ligands act at two binding sites within the GABAA-rho architecture. Future experiments will focus on additional characterization of these novel effects on GABAA-rho receptors and offer a novel chemical structure to design novel GABAA-rho therapeutics.Item PEDIATRIC CARDIOVASCULAR SCREENING RESEARCH(2014-03) Mou, Margaret; Wilson, Dr. DonAccording to current NIH guidelines, there should be universal screening of children ages 9-11 for cholesterol. By doing so, pediatricians can often detect familial hypercholesterolemia or high cholesterol that leads to future heart disease. However, many pediatricians currently are not following these guidelines. This project is to determine why that is the case and what changes can be implemented to help universal screening. Purpose (a): The objective of this project is to understand general pediatricians’ screening and treatment processes in children with a variety of cardiovascular disease risk factors, including what steps could be taken to ensure universal cholesterol screening of children ages 9-11. Methods (b): 1. Recruitment: Participants will be recruited via NLA pediatricians, contacted via email directly from the directors of these networks in order to maintain anonymity. 2. Data and Storage: Only the primary investigator will have access to the participating pediatrician’s responses to the questionnaire. The information will be imported directly from the submitted questionnaires, collated and stored on a secure online excel spreadsheet. 3. Procedures to Maintain Confidentiality: Because the directors of the participating networks are sending out the questionnaire on behalf of the study investigators, there is no direct trail from the primary investigator to the respondents. Thus, anonymity is maintained, and all the submitted information will remain confidential to the individual. 4. Data Security: Access to the excel spreadsheet will be password restricted to only the study’s primary investigator(s). Results (c): Briefly speaking, the majority of respondents do not currently order cholesterol screenings for their patients. However, 83% of the respondents do think that universal screening of cholesterol of children ages 9-11 years old is important. The major barriers seen by providers included family hesitancy and financial restrictions. Conclusions (d): There are opportunities to capitalize on the barriers for universal cholesterol screening in children ages 9-11, including provider education on current NIH guidelines, insurance policy, and family education.Item MOBILE INTERDISCIPLINARY GERIATRIC HEALTHCARE IN THE COMMUNITY(2014-03) O'Jile, Judith R.; Aaron, Debra; Buckley, Brielle; Sallee, Donna; Large, Stephanie E.; Johnson, Leigh; O'Bryant, Sid E.Purpose (a): This is a community-based geriatric primary care model designed to reach Medicaid eligible elders as well as childless adult “near elders” (ages 50-64) using mobile teams and clinics to reduce hospitalizations, increase access to care, and improve patient quality of life. This is a new initiative for UNTHSC that utilizes mobile teams and clinics to increase access to care by providing appropriate care within the community. Medical teams, led by physician assistants (PAs) or nurse practitioners (NPs), that incorporate Community Health Workers (CHWs) and others (pharmacy, physical therapy, social work), will provide care to patients within community settings and clinics. Additionally, CHWs will educate elders about Medicaid and assist with enrollment when necessary. The Community Health Workers will also provide case management to high risk patients.To meet the urgent care needs of our patients and reduce ER utilization, a nurse advice telephone line has been created for patients to call when they have urgent care issues or questions. This enhancement of geriatric primary care services will expand encounters to a significant portion of Medicaid- eligible elders within RHP 10. Methods (b): The MIGHTY Care program will see 3071 patients and roughly 15,000 encounters over the five year grant. Our program goals include decrease in admission rates, decrease in 30 day re-admission rates for preventable causes, increase in patient satisfaction regarding patient involvement in medical decision making, and increases in quality of life. The team identified several steps that must be completed in order to achieve the project goals, which included identifying stakeholders, geocoding population demographics in order to determine the best sites for our standing clinics, proper training on tenets ofshared decision making and customer service, community outreach, and others. Results (c): The primary community stakeholders identified were Senior Citizen Services, Goodwill Industries, and the Community Food Bank. We had several meetings with these facilities to discuss the potential of setting a community based clinic in their locations. Additionally, the team has conducted community talks, flu shot clinics, and other community outreach presentations. In preparation for seeing patients at these sites, we are deepening our relationships by providing educational programs for patients and staff members. At this time we are continuing to develop other possible candidates for alliances. Conclusions (d): The MIGHTY Care program offers an innovative solution to many of the issues that plague our current system. We will provide cost-saving community-based care that will improve patient outcomes and the patients’ satisfaction with their care.Item GENETIC POLYMORPHISMS AFFECTING CLOPIDOGREL METABOLISM(2014-03) Jain, Adityanant; Bruchetta, Humberto49 yo Asian male with history of coronary artery disease, hyperlipidemia, complete heart block, unstable angina pectoris and gout presents with four prior myocardial infarctions within the prior year indicating rapid stent restenosis despite being on dual anti-platelet therapy with clopidogrel and aspirin. Family history is very positive for myocardial infarctions and death on his paternal side. Patient is a lifetime non-smoker, employed as a hospital pharmacist and had no other cardiac risk factor besides family history. Physical exam was unremarkable, BMI 24.84, vital signs all normal. LDL was above goal at 83 and HDL was 61. A lipoprotein subfractionation, apolipoproteins, inflamatory markers, and genetic markers including LPA Aspirin, KIF6 Genotype, and CYP2C19 were obtained. Patient was noted to be homozygous KIF6 Arg/Arg and CYP2C19*2/*2. KIF6 Arg/Arg is associated with HR 1.50 for recurrent MI by the CARE trial, and clopidogrel is a pro-drug that requires CYP2C19 activation to be efficatious. The patient was changed to ticagrelor which has similar efficacy however does not require CYP2C19 activation. This case study strongly indicates a potential benefit for genetic screening for CYP2C19 on patients being placed on dual antiplatelet therapy with clopidogrel and aspirin. Further it shows the value of research in basic sciences to understand the causes variable responses to drugs in vivo. Purpose (a): To demonstrate a case of severe cardiovascular complications in a young and otherwise healthy patient with no high risk behaviours likely due to a genetic polymorphism affecting his ability to activate clopidogrel. Methods (b): Labs were drawn in the office and performed by Quest Lab and results were discussed with the patient who participated in decision making regarding his subsequent medication selection. Results (c): HR = "High Risk" LR = "Low Risk" MR = "Medium Risk," LPA Aspirin Genotype Ile/Ile (non-carrier), KIF6 Genotype Arg/Arg (High Risk-CV disease), 9p21 rs10757278 ag, 9p21 rs1333049 gc, ApoE Genotype E2/E3 (Apo E2 carrier), LPA Intron 25 Genotype tt (non-carrier), CYP2C19 *2/*2 (poor metabolizer), 4q25 AF Risk Genotype, rs2200733 tt (High Risk carrier - Afib & CVA), rs10033464 gg (non-carrier), HS-CRP 0.5, LP PLA2 181(LR), Fibrinogen Antigen 267 ≤ 350 (LR), Vitamin D, 25-OH, Total 18 ≥ 30 (HR), Vitamin D, 25-OH, D3 18, Vitamin D, 25-OH, D2 <4, Homocystine 16.1, Apolipoprotein A1 166 >176 (MR), Apolipoprotein B 62(MR), Apolipoprotein B/A1 0.37, Lipoprotein (a) 46(LR), Lipoprotein Subfractionation, LDL Phenotype A (LR), LDL, Particle Size 225.6 (LR) >255.5, LDL Particles, Tot 1234 (LR) <1260, LDL, Very Small 304 (LR) <398, LDL, Med & Small 397 (MR) <369, HDL, Small 28160 (LR) >28133, HDL, Large 8028 (MR) >9386, IDL, Small 223 (HR) >315, IDL, Large 179 (LR) <198, VLDL, Small 72 (LR) <124, VLDL, Medium 46 (LR) <61, VLDL, Large 13 (LR) <17. Conclusions (d): Our patient had multiple risk factors for underlying cardiovascular disease – including his KIF6 Arg/Arg genotype and strong family history. Although his CYP2C19*2/CYP2C19*2 genotype was not responsible for his underlying disease; significant evidence exists demonstrating that loss of function mutation being associated with adverse cardiovascular outcomes while on clopidogrel. Currently gene testing is not currently standard of care. Previous studies have not categorically shown cost-effectiveness of gene testing, however genetic testing technology is becoming increasingly affordable. Cost-effective gene testing and the availability of alternatives to clopidogrel suggests that identification of patients with loss of function mutations is in the best interest of patient care. If a patient has a thrombotic event on clopidogrel, it is appropriate to either determine CYP2C19 genotype or empirically initiate alternative antiplatelet therapy.Item BMP4 INDUCED ID PROTEIN PROTECTS TM FROM GLAUCOMATOUS EFFECTS OF TGFβ-2(2014-03) Mody, Avani A.; Wordinger, Robert J.; Clark, Abbot F.Insight into the BMP4 pathways in various disease models and different cell types has shown BMP4 to be a potent inducer of inhibitor of DNA binding proteins (ID1 and ID3). ID1 and ID3 are negative regulators of basic Helix loop Helix (bHLH) transcription factors and are known to control specific gene expression, including extracellular cellular matrix (ECM) genes. We previously have shown that BMP4 attenuates the pathogenic effects of TGFβ2 in the TM, an ocular tissue involved in regulation of intraocular pressure in glaucoma. We hypothesize that BMP-4 attenuates the effects TGFβ2 in the TM by inducing ID1 and ID3 expression. In our current study, we show that BMP4 induces ID1 and ID3 expression in TM cells. Over-expression and knockdown of ID1 and ID3 in TM cells show that ID1 and ID3 play a crucial role in attenuating the profibrotic effects of TGFβ2 in TM cells. Purpose (a): Increased aqueous humor (AH) outflow resistance causes high intraocular pressure (IOP), which is a critical risk factor in primary open-angle glaucoma. Elevated transforming growth factor b2 (TGFβ2) in the AH of glaucoma patients increases extracellular matrix (ECM) protein deposition in the trabecular meshwork (TM), thereby elevating IOP. Bone morphogenetic protein 4 (BMP4) inhibits the pathogenic effects of TGFβ2 in the TM. However, the underlying molecular mechanism for this BMP4 inhibition remains unknown. BMP4 regulates various cellular processes by induction of inhibitors of DNA binding proteins (ID1, ID3), which are transcriptional regulators that bind specific transcription factors and suppress their functions. This study will determine whether ID1/ID3 are downstream targets of BMP4, attenuating the TGFb-2 effects on TM cells. Methods (b): Cultured primary human TM cells and the GTM3 cell line were treated with BMP4 (5-10ng/ml) for 1-48 hrs. Q-PCR and western immunoblotting were performed to determine ID1 and ID3 expression. GTM3 and primary TM cells were transfected with ID1 and ID3 expression plasmids vectors or ID1 and ID3 siRNA to determine the effects of ID1 and ID3 on TGFβ2 induced extracellular matrix (ECM) proteins. The expression of fibronectin and plasminogen activator inhibitor-1 (PAI-1) was studied by western immunoblotting. Results (c): BMP4 induced ID1 and ID3 expression in TM cells. ID1 and ID3 suppressed the TGFβ2 induction of ECM proteins in TM cells, and therefore are key signaling molecules involved in the BMP4 suppression of TGFβ2 profibrotic activity. These specific regulators controlling TGFβ2 effects in the TM may lead to the development of potential new IOP lowering therapies for the treatment of glaucoma. Conclusions (d): BMP4 induced ID1 and ID3 expression in TM cells. ID1 and ID3 suppressed the TGFβ2 induction of ECM proteins in TM cells, and therefore are key signaling molecules involved in the BMP4 suppression of TGFβ2 profibrotic activity. These specific regulators controlling TGFβ2 effects in the TM may lead to the development of potential new IOP lowering therapies for the treatment of glaucoma.Item ISCHEMIA-INDUCED REDUCTION OF SOMATOSENSORY INPUT DECREASES BALANCE; ADDED VIBRATORY NOISE PARTIALLY RESTORES FUNCTION(2014-03) Rose, Gemma; Nordon-Craft, Amy; Jaffari, Roozbeh; Patterson, Rita M.; Bugnariu, NicoletaIn this project we mimicked loss of sensation in the feet, commonly seen in diabetic patients, through an ischemic protocol, a reduction of circulation in young healthy adults. This loss of sensation resulted in changes in balance like those seen in diabetic patients that are prone to falls. We then tested the effectiveness of a vibratory device to improve balance. Purpose (a): We investigated the feasibility of using vibrotactile biofeedback to improve balance in healthy young adults in which the somatosensory information from their feet has been temporarily decreased. We hypothesized that though stochastic resonance, vibratory noise applied just proximal to a region of reduced somatosensation will improve ability to maintain balance. Methods (b): Ten healthy young individuals aged 18 to 25 years old gave informed consent and participated in this study. We experimentally induced “somatosensory loss” in non-diabetic young healthy subjects using pressure cuffs wrapped around the ankles, kept inflated at 220-250mmHg for 35 min. A vibrotactile biofeedback system was positioned just above the pressure cuffs. An array of vibrotactile actuators, under a Texas Instruments MSP430 microcontroller, produced vibration at two frequencies: a barely perceptible low frequency and a high vibration frequency. Data was collected at baseline before the pressure cuffs were inflated and during the last 15 minutes of the ischemic protocol under three conditions: no vibration, low frequency and high frequency vibrations. Outcome measures included: centre of pressure (COP) variability with subjects standing with feet side by side/ one foot, with eyes open/closed; plantar surface pressure sensation and vibratory threshold evaluated with Siemens Monofilaments and Rydel-Seiffer tuning fork, respectively. Results (c): In single limb support with eyes closed, ischemia increases the COP variability (p=.01) and the addition of vibrotactile feedback at both frequencies decreases it baseline values. Plantar surface pressure sensation threshold increased after ischemia (p=.03) and was decreased with the added vibrotactile feedback. The vibratory extension threshold measured at the hallux IP joint was decreased by ischemia (p. Conclusions (d): The ischemic protocol produced balance changes in healthy young adults. The vibratory biofeedback was able to partially compensate for the experimental induced sensory loss and improve balance function. Most diabetic patients become “visually dependent” due to peripheral neuropathy, and may experience falls at night or when they turn their head or talk to someone while walking. The next step of this research is to test the effectiveness of a vibrotactile biofeedback to decrease the risk for falls in diabetic adults with peripheral neuropathies.Item DOES RESEARCH TOPIC OF INTEREST DIFFER BY GENDER AND RACE/ETHNICITY? RESULTS FROM THE NORTEX REGISTRY PROJECT.(2014-03) Shabu, Tanjina; Fulda, Kimberly; Espionza, Anna; Roberto CardarelliThis study is being conducted to assess the difference in research interest between race and gender. Ultimately this will help the NorTex researchers to conduct research in the areas of interest to the community. Purpose (a): NorTex is a collaboration of over 110 clinics that conduct research important to primary care, public health, and the community. The purpose of the NorTex Registry Project (NRP) is to develop and maintain a database of individuals who may be contacted for future NorTex studies. The current study examined gender and racial/ethnic differences in research topics of interest for diabetes, cardiovascular disease, cancer, and mental health among NRP participants. Methods (b): Patients 18 years or older at participating clinics may complete a 4X6 index card (English or Spanish) giving permission to be contacted for NorTex studies. Index cards include contact information, demographic information, medical problems, and topics on which the participant would like more research conducted. Chi-square analysis was performed to determine differences in cardiovascular disease, diabetes, cancer, and mental health research interest by gender and race/ethnicity. Results (c): The NRP includes a total of 1285 participants. Of these, 901(70.1%) are female, 470(36.6%) are Caucasian, 409(31.8%) African American, 297(23.1%) Hispanic, and 109(8.5%) other. 265(76.6%) males and 612(68.3%) females (p=0.004) are interested in cardiovascular disease (CVD) research. 189(54.6%) males and 417(46.5%) females are interested in diabetes research (p=0.011). Racial/ethnic differences exist for interest in diabetes (p<0.001) and mental health (p=0.001) research. No other differences were observed. Conclusions (d): There is a significant difference in research interest between races/ethnicities for diabetes and mental health. Gender differences exist for interest in cardiovascular disease and diabetes. These findings will allow NorTex to conduct research in areas of interest to the community.Item SLEEP APNEA AND ITS ROLE IN OXIDATIVE STRESS AND INFLAMMATION(2014-03) Snyder, Brina; Cunningham, J. Thomas; Cunningham, Rebecca L.Inflammation has been linked with sleep apnea. Sleep apnea is a common comorbidity associated with Parkinson’s disease. Furthermore, both sleep apnea and Parkinson’s disease have been linked with inflammation. A possible mechanism underlying increased inflammation in these disorders is oxidative stress, a hallmark of many neurodegenerative disorders. To examine the role of oxidative stress on inflammation, we used chronic intermittent hypoxia (CIH), an established model for the hypoxemia associated with sleep apnea. CIH consists of recurring events of low oxygen followed by reoxygenation. We hypothesize that CIH causes oxidative stress, which induces inflammation. To test this hypothesis, plasma from adult male rats subjected to 7 days of CIH (3 minute periods of hypoxia (10% oxygen) and 3 minute periods of normoxia (21% oxygen) for 8 hours per day) or normoxia (room air) was tested for AOPP, an indicator of oxidative stress, and circulating inflammatory markers (IL-10, IL-4, IL-6). Our results showed that CIH significantly increased circulating oxidative stress. These results were then correlated with inflammatory markers in the plasma and statistically analyzed for positive associations. IL-6 was found to be significantly increased in CIH, although not associated with oxidative stress. However, CIH did increase IL-4 and IL-10, and these effects were positively associated with circulating oxidative stress. Inflammatory markers IL-4 and IL-6 are generally associated with macrophage-mediated inflammation. Therefore it is possible that CIH-induced oxidative stress underlies macrophage mediated inflammation. These findings suggest that sleep apnea increases oxidative stress and consequently inflammation.Item SRC-KINASE MEDIATES ANGIOTENSIN II INDUCED POTENTIATION IN TRPV4 AGONIST EVOKED CALCIUM TRANSIENTS IN HYPOTHALAMIC IMMORTALIZED NEURONAL CELL LINE 4B(2014-03) Saxena, Ashwini; Bachelor, Martha E.; Carreno, Flavia R.; Cunningham, J. ThomasWe have previously demonstrated that in bile duct ligated rats, an animal model of inappropriate vasopressin (AVP) release, TRPV4 protein expression and membrane trafficking is increased in AVP neurons. Here, we used an in vitro approach with an immortalized AVP expressing neuroendocrine cell line (4B neurons) to investigate the possible regulation of TRPV4 by angiotensin II (Ang II). We characterized the presence of TRPV4 mRNA and protein in 4B cells. Ang II (100nM;1 hr) treatment significantly increased TRPV4 abundance (p. Purpose (a): ØInappropriate Vasopressin (AVP) release causes dilutional hyponatremia associated with heart and liver failure. Although the central molecular mechanisms that mediate inappropriate AVP release are not clear, plasma angiotensin II (Ang II) has been implicated as a factor in the pathogenesis of dilutional hyponatremia. Our previous studies using a rodent model of liver failure, have shown that increased TRPV4 expression in vasopressinergic neurons and elevated circulating AVP were blunted by normalization of the renin angiotensin system (RAS). Effects of circulating Ang II on neural networks may mediate cellular adaptations associated with changes in TRPV4 expression and/or sorting ØBased on our in vivo studies we speculate that modulation of transient receptor potential vanilloid (TRPV4) channels by means of changes in its membrane sorting could alter its gating, and thus contribute to changes in neural excitability that would be consistent with increased AVP release in rats with liver failure. To examine the effects of AngII treatment upon TRPV4 we utilized the rat hypothalamic AVP expressing neuronal cell line 4B. Methods (b): We used Western Blots to detect changes in TRPV4 protein in membrane fraction after drug treatments. In addition, we used calcium sensitive dye Fura 2-AM to detect changes in intracellular calcium after administration of a selective TRPV4 agonist - GSK 1016790A. Results (c): We characterized the presence of TRPV4 mRNA and protein in 4B cells. After Ang II (100nM;1 hr) treatment significantly increased TRPV4 levels in crude membrane fractions (p<0.001) and tyrosine phosphorylation of TRPV4 (p<0.001). Using calcium sensitive dye Fura-2AM, we noted that Ang II treated cells exhibited increased calcium transients in response to TRPV4 agonist, GSK1016790A (20nM, p<0.05). This increase was blocked by the Losartan (Ang II receptor antagonist) and Src-kinase inhibitor, PP2, but not by its analog PP3. Conclusions (d): Our data indicate that Ang II may facilitate TRPV4 trafficking and alter the phosphorylation status of TRPV4 through Src-kinases.Item THE EFFECT OF LS-1-137, A NOVEL PHENYLACETAMIDE SIGMA 1 RECEPTOR SELECTIVE AGONIST ON SCOPOLAMINE-DEPENDENT COGNITIVE DEFICIT IN C57BL/6J MICE.(2014-03) Malik, Maninder; Rangel-Barajas, Claudia; Griffin, Suzy; Sumien, Nathalie; Singh, Meharvan; Maurice, Tangui; Mach, Robert; Luedtke, Robert R.Cognitive deficits are observed in aged population and in patients with Alzheimer’s Disease, Parkinson’s Disease, traumatic brain injury and stroke. Cognitive deficits often involve alterations in brain signaling. Currently available therapeutic drugs provide only symptomatic relief and generally become ineffective as disease progresses. Therefore, novel therapeutic agents are needed to retard and/or arrest the progressive loss of memory forming cells. Scopolamine-induced memory impairment model provides a relatively rapid and reversible screening paradigm for cognition enhancement drug discovery. In this study, mice were administered scopolamine and were used to evaluate the ability of LS-1-137, a novel drug, to improve the cognitive deficits. Our study results indicate that LS-1-137 may represent a novel therapeutic agent for the treatment of age and disease related cognitive deficits. Purpose (a): Cognitive deficits are observed in patients with Alzheimer’s Disease, Parkinson’s Disease, traumatic brain injury and stroke. These deficits often involve alterations in cholinergic signaling. Currently available therapeutic drugs provide only symptomatic relief and generally become ineffective as a neurodegenerative disorder progresses. Therefore, novel therapeutic agents are needed to retard and/or arrest the progressive loss of memory forming cells. Methods (b): A filtration-binding assay was used to characterize the binding properties of a novel sigma compound at D2-like dopamine receptors, muscarinic receptors and at sigma receptors. Co-immunoprecipitation assay was used for the quantification of Sigma 1 receptor-binding immunoglobulin protein (BiP) complex formation. LS-1-137 mediated brain-derived neurotrophic factor (BDNF) release was analyzed using enzyme-linked immunosorbent assay (ELISA). In this study, male C57BL/6J mice injected with scopolamine were used as experimental model to evaluate the in vivo cognitive properties of the test drug. The neuroprotective properties were evaluated using water maze and active avoidance test. Results (c): LS-1-137 binds with high affinity (Ki = 3.2 nM) at sigma 1 receptors and is 80-fold selective for sigma 1 compared to sigma 2 receptor. LS-1-137 binds with low affinity at D2-like (D2, D3 and D4) dopamine and muscarinic receptors. LS-1-137 was found to partially reverse the learning and memory deficits associated with scopolamine administration using a water maze test and an active avoidance task. LS-1-137 treatment modulates sigma 1 receptor- BiP complex formation and also triggers the release of BDNF from rat astrocytes. Conclusions (d): LS-1-137 may represent a novel candidate cognitive enhancer for the treatment of cholinergic muscarinic-dependent cognitive deficits.Item PROMOTING HEALTHY PREGNANCY BEHAVIORS AMONG KAREN BURMESE REFUGEES(2014-03) Board, Amy; Raines-Milenkov, Amy; Thein, Emelda; Anderson, RalphPurpose (a): To identify baseline understanding of healthy pregnancy behaviors as well as gaps in knowledge and access to pregnancy-related care for Karen Burmese refugee women in Fort Worth. Methods (b): Focus groups were designed to identify the baseline level of pregnancy knowledge and access to care. Discussion with key players in the Karen community led to the selection a natural leader within the population to conduct the focus groups, which were held on two different days and times in the apartment complex where the majority of the population resides. Results (c): Respondents shared both positive and negative reactions regarding delivering a baby in the U.S based upon their personal experiences or stories they had heard from friends and relatives who had given birth. Positive responses included the ability to receive an epidural to relieve labor pain, access to prenatal vitamins, vaccines, and medicines, and the sentiment that in America, doctors are able to use tests and technology to make sure the baby receives good care. Negative responses included a lack of proper or culturally sensitive interpretation at provider visits, lack of proper information sharing by staff about the purposes of and alternatives for medical procedures, and long wait times at the hospital before receiving care. Barriers cited to receiving proper care include transportation, lack of insurance coverage, limited English proficiency, and anxiety about not being able to navigate the health system. Conclusions (d): Karen Burmese women in Fort Worth view the American health care system with a mixture of gratitude and trepidation. Full integration and use of this system for early access to prenatal care will involve outreach and education efforts among the Karen as well as greater understanding and flexibility on the part of health care providers.Item WHAT ARE THE NEEDS OF PERMANENT SUPPORTIVE HOUSING RESIDENTS? A SURVEY OF CASE MANAGERS IN TARRANT COUNTY(2014-03) Marshall, Brittany; Walters, Scott; Spence-Almaguer, Emily; Abraham, StacyThis research served as a pilot study to help us develop a program for homeless persons in Tarrant County to improve their quality of life. Purpose (a): Permanent Supportive Housing (PSH) is used as a method of reducing homelessness and its associated costs. The insight of case managers is integral to determine factors that may facilitate or inhibit the health and quality of life of PSH residents in Tarrant County. Methods (b): An online survey was conducted with PSH case managers (n=24) to assess the percentage of PSH residents affected by various health and wellness domains, barriers to improving health, and potential motivational levers. Data was analyzed using SPSS. Results (c): Case Managers reported that clients were most affected by poor mental health (74%), poor social support (69%) physical health (64%) and substance abuse (46%). Case managers identified furniture, transportation, and food as their clients’ top needs. Case managers believed clients were somewhat motivated to work on improving social support, physical and mental health, and poor nutrition. Approximately 60% of case managers believed their clients were not at all or a little motivated to work on improving medication adherence and substance abuse issues. Conclusions (d): Findings will guide the development of the Interactive Community Health Assistance for Tenants (iCHAT), which aims to reduce alcohol and drug use, reduce symptoms of depression, and improve quality of life amongst PSH residents.Item PROLONGED NMDA STIMULATION INDUCES NEUROPROTECTIVE PATHWAYS AND ENHANCES SURVIVABILITY OF PRIMARY RETINAL GANGLION CELLS(2014-03) Mueller, Brett H.; Park, Yong; Ma, Hai-Ying; Yorio, ThomasPurpose (a): Calcium influx through postsynaptic NMDA receptors has been shown to stimulate a number of key pro-survival genes; however, prolonged stimulation has been shown to have excitotoxic effects leading to apoptosis in neurons. Previous studies have shown a rapid dephosphorylation of CREB in primary hippocampal neurons treated for 1-2 h with100µM NMDA . It is hypothesized that the activation of CREB-specific phosphatases is one of the main pathways that cause apoptosis during NMDA excitotoxicity. The current study investigated the role of NMDA stimulation on the phosphorylation of CREB in primary RGCs, and assessed if NMDA overstimulation caused excitotoxic changes similar to those seen in primary hippocampal neurons. In addition, the occurrence of NMDA excitotoxicity in bipolar and photoreceptor cells was also investigated. Methods (b): Purification and culture of RGCs were performed by sequential immunopanning using Thy 1 antibody from P3-P7 Sprague-Dawley rats. Mixed retinal cultures that remained following isolation of RGCs from the retina were plated once the RGCs were separated and purified. Calcium imaging was used to measure the intracellular changes in calcium following treatment of cells with 100µM NMDA. Western blots were performed to determine signaling pathways linked to NMDA induced cell survival or excitotoxicity. Calcein AM and ethidium homodimer were used to quantify cell survival and cell death. Cells were also subjected to a trophic factor deprivation insult for 6 hours and 24 hours. Results (c): Treatment of primary RGCs with NMDA (100 µM) for 6h caused a greater than 2-3 fold induction of the transcription factor pCREB. MK801 (NMDA antagonist) completely abolished endogenous levels of pCREB and blocked NMDA induction of pCREB. NMDA (100 µM) treatment for 6 and 24 hrs under trophic factor deprivation, protected RGCs from trophic factor deprivation induced cellular death. The mixed retinal cultures (retinal cells without RGCs) had an opposite effect, where the levels of pCREB were diminished and the neurons died when treated with 100 µM of NMDA. Conclusions (d): The data suggests that NMDA signaling is essential for RGC survivability and blocking calcium ion influx through this receptor by the NMDA blocker, MK801 can be detrimental to RGC function and survival. These results also demonstrate that primary RGCs behave differently than other neurons in the retina, and are not susceptible to NMDA excitotoxicity.Item PATERNAL RACE/ETHNICITY AND VERY LOW BIRTH WEIGHT AMONG WOMEN IN TARRANT COUNTY, TX 2006-2010(2014-03) Fulda, Kimberly G.; Kurian, Anita K.; Balyakina, Elizabeth S.; Moerbe, Micky M.Low birth weight, including very low birth weight (<1,500 grams), is not evenly distributed across racial/ethnic groups. Although the reason for this is not completely understood, recent research has emphasized the need for a more comprehensive understanding of paternal influences on racial/ethnic birth disparities. This study looked at the association between paternal race/ethnicity and very low birth weight (VLBW) stratified by maternal race/ethnicity. Results show that paternal race/ethnicity is an important predictor of VLBW among white and Hispanic mothers. Future research should consider paternal race/ethnicity and further explore the association between paternal characteristics and VLBW. Purpose (a): The purpose was to examine the association between paternal race/ethnicity and VLBW stratified by maternal race/ethnicity. Methods (b): Birth data for Tarrant County, Texas 2006-2010 were analyzed. VLBW was dichotomized as yes (<1,500g) and no (≥1,500g). Paternal race/ethnicity was categorized as white, African American (AA), Hispanic, other, and missing. Missing observations (14.7%) were included and served as a proxy for fathers absent during pregnancy. Potential confounders included maternal age, education, and marital status, plurality, previous preterm birth, sexually transmitted disease during pregnancy, smoking during pregnancy, and Kotelchuck Index of prenatal care. Logistic regressions were stratified by maternal race/ethnicity. Odds ratios and 95% confidence intervals were calculated. Results (c): Of 145,054 births, 60,156 (41.5%) were white, 22,306 (15.4%) AA, 54,553 (37.6%) Hispanic, and 8,039 (5.5%) other mothers. There were 2,154 (1.5%) VLBWs total, with 3.1% for AA mothers and 1.2% for all other race/ethnicities. Among white mothers, AA paternal race was associated with increased odds of VLBW (OR=1.52; 95% CI:1.08-2.14). Among Hispanic mothers, AA paternal race (OR=1.66; 95% CI:1.01-2.74) and missing paternal race/ethnicity (OR=1.65; 95% CI:1.15-2.36) were associated with increased odds of VLBW. Conclusions (d): Paternal race/ethnicity is an important predictor of VLBW among white and Hispanic mothers. Future research should consider paternal race/ethnicity and further explore the association between paternal characteristics and VLBW.Item EFFECT OF TIBIAL SLOPE ON FLEXION AND FEMORAL ROLLBACK IN TOTAL KNEE ARTHROPLASTY: A CADAVERIC STUDY(2014-03) Chambers, Andrew W.; Wood, Addison; Kosmopoulos, Victor; Sanchez, Hugo; Wagner, RussellPurpose (a): Reduced posterior tibial slope (PTS) and posterior tibiofemoral translation (PTFT) in posterior cruciate retaining (PCR) total knee arthroplasty (TKA) has been shown to result in suboptimal postoperative knee flexion due to the occurrence of tibiofemoral impingement. Although reduced PTS and PTFT have been shown independently to negatively affect total knee flexion following TKA, there has never been a study to our knowledge that has shown the effect of PTS on PTFT. We evaluated the relationship between PTS, PTFT, and total knee flexion in a cadaveric model after TKA. Methods (b): We obtained nine transfemoral fresh frozen cadaver specimens and preformed a balanced PCR TKA. The pre-operative and post-operative PTS were precisely measured with c arm fluoroscopy and the post-operative PTS was changed in 1 degree increments using custom shims for the TKA trial components. We successively measured the total flexion using a motion tracking system in response to a 25 lb force applied to the hamstrings at 1 degree increments of posterior tibial slope (1-10 degrees). Relative PTFT was measured at maximal flexion with C-arm fluoroscopy. Results (c): We used Tukey ANOVA test to determine significant changes in flexion and PTFT as a function of PTS. We found that there was an average increase in flexion of 2.3 o per degree increase of PTS from 1o (1 degree) to 5 o (p. Conclusions (d): Small increases in PTS in the range of 1o to 5o appear to significantly increase knee flexion and PTFT. As the PTS is further increased above 5 o, these findings suggest that flexion and PTFT do not continue to increase significantly. This is the first study to find a direct relationship between PTS and PTFT. These findings may be explained by changes in PCL tension with different PTS. As the flexion gap is loosened above a threshold (5 o) with increased PTS, the relatively lax PCL likely fails to initiate PTFT and subsequent total knee flexion is subsequently decreased due to posterior tibiofemoral soft tissue impingement. Additionally, we did not observe a correlation between native PTS and optimal degree of post-operative PTS. Although these results suggest that increasing PTS above 5o does not improve flexion or PTFT, clinical judgment and proper flexion gap balancing remain paramount in maximizing post-operative knee flexion. In vivo studies will be necessary to further substantiate these conclusions.