2016
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Item Increased duration of isoflurane exposure reduces cerebral infarct and improves neurological function in focal cerebral ischemia in rats(2016-03-23) Gaidhani, NikhilIsoflurane is a widely used gas anesthetic for surgical procedure in rodents. Using a rodent model of transient ischemic stroke (transient midcerebral artery occlusion; tMCAO) our laboratory has demonstrated that longer exposure period to isoflurane anesthesia significantly reduce cerebral ischemic damage. The objective of this study was to demonstrate the correlation between the duration of isoflurane exposure and isoflurane-induced neuroprotection after tMCAO. Three groups were created based on total duration of isoflurane exposure during tMCAO and rats were randomly assigned to these groups; Isoflurane-20 min, Isoflurane-40 min, and Isoflurane-90 min. Focal cerebral ischemia was induced by a transient (90 min) middle cerebral artery occlusion in the rats from each group. Measurements of cerebral infarct volumes and neurological behavioral tests were performed 24hrs post-MCAO. We report that rats from Isoflurane-20 min group sustained significantly larger cerebral infarct than animals from Isoflurane-40 min and Isoflurane-90 min groups. Rats from Isoflurane-90 min groups showed near complete resistance to ischemic damage. Neurological function also significantly improved with increased duration of isoflurane exposure as evidenced by the results of Bederson and Cylinder tests. Our results clearly demonstrate the neuroprotective effect of isoflurane during ischemic stroke and provide strong evidence that increasing the duration of isoflurane exposure during the tMCAO procedure significantly reduce brain injury and improve neurological function after focal cerebral ischemic stroke.Item Homer Mediates Vascular Store-Operated CA2+ Entry and is Required for Neointima Formation after Vascular Injury(2016-03-23) Jia, Shuping; Wu, Qiong; Williams, Arthur Jr.; Little, Joel; Cunningham, Joseph; Mifflin, Steve; Ma, Rong; Yuan, Joseph; Rodriguez, MiguelOcclusive arterial disease (OAD) refers to the pathological obstruction of arteries that become progressively narrowed over time and are eventually blocked due to various risk factors, such as hypertension, diabetes, and atherosclerosis. This chronic arterial damage results from vascular wall remodeling, leading to neointima formation. Store-operated Ca2+ channels (SOCs) and entry (SOCE) play a central role in the vascular smooth muscle cell (VSMC) phenotypic change from contractile to migratory and proliferative states. In the present work, we ask if Homer is a critical molecular component of VSMC SOCE and does Homer mediate VSMC migration/proliferation and neointima formation. Homer binds to transient receptor potential canonical (TRPC) channels and is required for gating of TRPCs, while stromal interacting molecule1 (STIM1) binds to and regulates TRPC and Orai channels as SOCs. We cultured rat aortic VSMCs to increase their SOCE and migration/proliferation, as seen in OAD. Studies were done using small-interfering RNA (siRNA) targeting Homer1, STIM1, and TRPCs. Scratch wound migration assays were performed, and VSMC proliferation was assessed by cell count. In our in vivo OAD model (rat carotid artery balloon injury), the arteries were treated with adeno-associated virus (AAV) encoding short-hairpin RNA (shRNA) targeting Homer1. We found that Homer1 protein expression levels increase in balloon-injured vs. intact VSMCs, similar to known increases in protein expression levels of STIM1, Orai1, and TRPCs. Furthermore, we show that Homer1 binds to Orai1 and that interactions between Homer1 & Orai1/TRPCs and between STIM1 & Orai1/TRPCs markedly increase in injured vs. intact VSMCs. Cultured VSMCs treated with siHomer1 exhibit significant reduction in SOCE (56 ± 4.0%) vs. control (scrambled siRNA), similar to the SOCE reduction seen in siSTIM1-/siTRPC-treated cells. SiHomer1-treated cells also migrate significantly less over the wound surface area (73.3 ± 5.9%), and proliferate significantly less (73.3 ± 4.2%) vs. control, similar to observations seen in siSTIM1-/siTRPC-treated cells. Finally, immunofluorescence staining shows that the increased Homer1, STIM1, and Orai1 protein expression levels are localized in the neointima of the injured carotid artery. Knockdown of Homer1 using AAV-shHomer1 reduces this neointima. These studies provide evidence that Homer is a critical component of VSMC SOCE and neointima formation.Item Exploring Compassion Fatigue and Satisfaction Among Refugee Leaders in the DFW Area(2016-03-23) Raines-Milenkov, Amy DrPH; Kwentua, Victoria; Berg, ElyssaPurpose: Compassion fatigue describes the secondary traumatic stress seen in those working with others that have experienced trauma. It can lead to chronic fatigue, anxiety, irritability, and eventually burnout. Compassion fatigue has been studied in numerous helper and caregiver roles, such as social workers, nurses, and child protection caseworkers. However, research has not been conducted to investigate the presence of compassion fatigue within refugee populations or to understand how compassion fatigue may affect community leaders in this high-risk population. This study will explore the behavioral, emotional and physical effects of working with refugees among refugee leaders. Methods: In-depth qualitative interviews were conducted with refugee leaders working with refugees in the DFW area. Each participant completed a demographic questionnaire, a comprehensive interview and Professional Quality of Life Scale: Compassion Satisfaction and Compassion Fatigue Version 5 (ProQOL). The ProQOL questionnaire is a validated tool used to assess compassion fatigue. Results: Nine refugee leaders, representing six refugee groups, completed the demographic questionnaire, interview and ProQOL questionnaire. Participants reported a high level of compassion satisfaction (mean = 44.2), a low level of burnout (mean = 18.9), and a varied level of secondary traumatic stress. Refugee leaders reported a reliance on faith and a compulsion to help others due to their refugee experience as factors that outweighed the cost to their family wellbeing, physical and emotional health. Conclusions: Refugee leaders are highly resilient. They are often recruited by health care organizations, researchers and resettlement agencies to provide services and information to other refugees. These findings have implications for organizations to provide training on self-care practices and support services.Item Refugee Women’s Breastfeeding Practices and Experiences Following Resettlement in Tarrant County(2016-03-23) Raines-Milenkov, Amy; Baker, Eva; Kwentua, Victoria; Thein, Emelda; Mudey, Halimo; Subedi, Radhika; Rudasingwa, Laurette; Durbin, KatherinePurpose Exclusive breastfeeding for the first 6 months of life ensures that infants obtain adequate nutrients needed to support healthy growth and development. While there is robust literature on factors influencing breastfeeding initiation and duration among sub-populations of women, there is little known about the breastfeeding practices of refugee women resettled in the United States. The limited studies and anecdotal reports suggest, however, that breastfeeding practices change following resettlement. This qualitative study aims to explore refugee women’s infant feeding experiences and practices to better inform culturally appropriate education, support, and maternity care for women resettled in Tarrant County, Texas. Methods Refugee women between the ages of 18 and 50, who had given birth to at least one live infant were recruited into the study. Participants completed a demographic survey and participated in a focus group discussion about their breastfeeding practices and experiences. The demographic survey addressed participant age, ethnicity, time and experience breastfeeding, etc., and descriptive statistics were complied to assess the characteristics/demographics of the study population. Bilingual research personnel conducted focus groups in their respective language using a semi-structured interview guide exploring infant feeding practices, experiences, sources of information, etc. The group discussions were audio-recorded, translated and transcribed. Systematic procedures of qualitative data analysis included intensive reading of the text and group discussion of full transcripts, followed by coding, displaying, reducing, and interpreting information. Results Refugee women representing different ethnic groups participated in the demographic surveys and focus groups. Conclusions Results of the focus groups suggest multiple influences on infant feeding practices of refugee women following resettlement in the United States. A culturally and linguistically multi-level approach to providing education and support services to refugee women is necessary to protect their breastfeeding practices. Findings from this study have implications for health providers, resettlement agencies, public health and others involved in serving this population.Item The Impact of Guided Reflection in the Professional Development of Medical Students in the Context of Death and Dying.(2016-03-23) Martin, Roy; Knebl, Janice; Hsu, Jennifer; Marquez-Hall, SandraStatement of the Hypothesis Medical students often struggle with end-of-life issues. To address this need, two educational sessions about death and dying were introduced to fourth year medical students during their Core Geriatric Clerkship. The curriculum included the use of guided reflection, which involves facilitated discussion and reflective writing, to help students identify and cope with their feelings about death and dying. Many students had reported struggling to identify their role as a health professional related to the topic of death and dying. This study explores the impact of helping students reflect on their understanding of a medical professionals role in death and dying. Brief Summary of Materials and Methods The idea for this project originated from the results of a previous study conducted by the Reynolds Geriatric Education and Training in Texas (GET-IT) program. A pre- and post-survey was administered to fourth year students (n-805) prior to the start and again at the end of the 4 week Core Geriatric Clerkship. The survey found that students felt less comfortable discussing palliative care and end-of-life issues after exposure during the rotation (pre-test mean: 4.20, post-test mean: 3.59, p A Summary of the most pertinent, significant results As part of their core geriatrics clerkship, fourth year medical students were required to attend two sessions on end-of-life care that included lecture, guided discussion, community resources and a reflective writing assignment. The follow-up self-assessment survey greatest improvement in competency was end-of-life care. In the pre-test students had reported 1.96 average mean in their comfort level related to End of Life Care; and, after participation in the revised curriculum, students reported an average mean score of 3.02. This findings indicate that the average student now feels they have “significant ability” to talk about end-of-life issues. Conclusions derived from the presented data Fourth year medical students at UNTHSC were found to have struggled with communication related to palliative care and end-of-life issues. By providing a safe platform for review and communication on end of life issues, the study found that students reported improved confidence in the ability to cope with death and dying. While 150 minutes of instruction cannot fully prepare students to cope with these difficult and sensitive issues, students can gain confidence in this area of their professional role as future physicians. Through peer support and faculty feedback, the guided reflection increased students’ belief in their own competence, freeing them to use their unique life experiences and skills to cope with death and dying.Item Oral Health Status Among Drug Abusers(2016-03-23) Kolasani, Balaji; Nandy, Rajesh PhD; Mallampati, RajeshAbstract Purpose- To evaluate oral health status among drug abusers. Methods- We used data National Health and Nutritional Examination Survey (NHANES) data of 2011-2012 to examine the relationship between oral health and drug abuse. Drug abuse data included people who are using or used marijuana, cocaine, methamphetamine, heroin and injected drugs. Presence of decayed teeth, missing teeth which are not replaced and periodontal status are used as indicators of oral disease. We used SAS® 9.4 for our analysis. Logistic regression model was used to analyze the relationship while adjusting for demographic variables. Results- A total of 4116 participants from 18 to 69 years were used for our analysis purposes. Total number of drug users are 1916. No significant relation was detected between oral health and drug abuse (OR=0.942, 95% CL= 0.756, 1.176). Conclusion- Among the participants of our study which included 1916 drug abusers no significant difference in oral health status was observed.Item The Urgent Management of T-Cell Acute Lymphoblastic Leukemia (T-ALL) in Children(2016-03-23) Chhin, Rasmey; Heym, Kenneth; Bowman, Paul; Pham, ChristinaThe Urgent Management of T-Cell Acute Lymphoblastic Leukemia (T-ALL) in Children Purpose: Children with T-ALL often have aggressive disease with life-threatening problems at the time of diagnosis. This presentation of three cases describes the diagnostic process of T-ALL, discusses the clinical options involved in initial management, and delineates expectations for patients prior to discharge. This descriptive study highlights the most important steps in managing a patient with T-ALL and its associated complications. Method: Three recently diagnosed cases (late 2015) were available for study. Patient records were reviewed to gather information regarding history, physical exam, laboratory data, imaging, and management. Results: Each of these patients, ages 18 months, 3 years, and 10 years of age, had a different clinical presentation. They were referred to Cook Children’s Medical Center (CCMC) after evaluation by a primary care or urgent care provider. The suspicion of leukemia was confirmed with peripheral blood smears and flow cytometry. Two of the three patients had a mediastinal mass present. All patients presented with severe leukocytosis with white blood cell counts ranging from 425,000 to 781,000/mm3. Due to the concerns of leukostasis, they each underwent leukapheresis to decrease their white cell counts. Concerns addressed during admission included respiratory distress, cerebral leukostasis, and tumor lysis syndrome. These patients spent an average of eleven days in the hospital with each patient spending five days in the Pediatric Intensive Care Unit. Two were enrolled in a randomized clinical trial assessing the efficacy of investigational drug bortezomib in T-ALL. The patient that was not enrolled in the trial received the current standard of care. Conclusion: T-ALL (with or without mediastinal mass) can be the underlying cause of life threatening clinical problems. Although protocols are the backbone of treatment, there may be differences in the initial management, including the decision to utilize leukapheresis to bring WBC levels from initially dangerous elevations to values that are safer before beginning anti-leukemic therapy, as well as steroid preconditioning. Patients were discharged after evidence of clinical stability, treatment progress, and improvement in hematological lab values. In addition, each of these patients had family demonstrating commitment to follow up for additional treatment.Item Identifying Provider and Patient Barriers to the Implementation of (MeTree) Family Health History Clinical Decision Support (FHH CDS) Tools(2016-03-23) Cross, Deanna; Fulda, Kimberly; Espinoza, Anna; Zhang, Julia; Mallaiah, JanhaviObjective: The purpose of this study was to determine healthcare provider and patient barriers in the implementation of a FHH CDS tool. Background: The University of North Texas Health Science Center (UNTHSC) in collaboration with Duke University and other sites around the country is currently conducting an implementation-effectiveness study to investigate MeTree implementation. MeTree, a Family Health History Clinical Decision Support (FHH CDS) tool is a patient facing tool that provides disease risk-stratification to both patients and providers. In previous studies, several perceived barriers for the use of this type of tool were identified including limited time during a patient visit and a lack of patient knowledge to provide family health history. This is especially true in regard to primary care clinics that cater to underserved populations. Methods: Family Medicine providers from three primary care clinics were identified and recruited. Eligible patients of consented providers were invited to participate in the study via recruitment letters. Registration information was obtained from interested patients, and unique study IDs were assigned by study coordinators at UNT Health Science Center. Registered patients received an email link to e-consent and complete the family health history online using the MeTree software. A printed copy of the risk report generated on completion of MeTree was delivered to the primary care provider to be reviewed at their next clinical appointment. Results: To date, patients of two Family Medicine providers were invited to participate in the study. Of the 2711 who were invited, 92 patients registered (response rate 3.39%) and 11 patients completed MeTree (completion rate 11.9%). Qualitative information collected through in-person discussions with providers indicated a preference of integration of the risk stratification report into the electronic medical record (EMR) system versus a printed copy of the report. Patient barriers included lack of access to a computer and internet. Conclusion: Provider engagement in implementation of new clinical decision support tools is imperative for identifying barriers as well as providing potential solutions for these barriers.Item Epidemiology of Hip Fractures, a Retrospective Review(2016-03-23) Davis, Jacob; Sanchez, Hugo; Fairbanks, CarsonPurpose: To determine the epidemiology and fracture characteristics of hip fractures at a level two trauma center. To establish a hip fracture database to further research on the subject. Methods: An IRB exempt retrospective chart review was undertaken on consecutive patients 55 years of age and greater from December, 2010 through July, 2013 who sustained a proximal femur fracture from a ground level fall. All of these patients underwent operative fixation at a single, urban, level two trauma center. X-rays were reviewed by three Orthopedic surgeons blinded to patient identification and were characterized using the AO/OTA classification system into fractures of the femoral neck (FN), intertrochanteric region (IT), and subtrochanteric region (ST). Fracture classification and fixation method were recorded and combined with clinical information from the hip fracture database. Results: There were 986 patients that met study characteristics including 281 (28.5%) males and 705 (71.5%) females, the average age was 79.5 years old. Fracture characteristics included 91 (9.2%) non displaced FN, 332 (33.7%) displaced FN, 275 (27.9%) stable IT, 169 (17.1%) unstable IT, 82 (8.3%) reverse obliquity IT, 28 (2.8%) ST, and 9 (0.1%) peri-prosthetic fractures. The average length of stay was 5.9 days (range 1-36 days), and the most common discharge destinations were 526 (53.35%) patients to a skilled nursing facility and 303 (30.7%) to a rehabilitation facility. Only 76 (7.7%) of patients were discharged home. The in hospital mortality rate was 1.6% (16 patients). Conclusion: Hip fractures in the geriatric population are very common and lead to significant morbidity, mortality, and loss of pre-injury functional level. Understanding the epidemiology of these fractures will better guide patient care and allow us to formulate treatment protocols to best serve this vulnerable patient population. Further research should continue on, among other things, the appropriate types of fixation for these fractures, factors that influence length of stay, and ways to improve function after hip fracture. The aim of this research should be to reduce the physical, psychological, financial, and social burden that hip fractures have on both patients and society as a whole.Item Improving Lives of Most Vulnerable: The Relationship between Diet, Physical Activity, and Quality of Life among Permanent Supportive Housing Residents(2016-03-23) Suzuki, Sumihiro; Spence-Almaguer, Emily LSW, PhD; Walters, Scott PhD; Chhetri, ShlesmaBackground: Chronic homelessness is a complex public health concern in the United States. People experiencing chronic homelessness are much more likely to suffer from mental illness and substance use, and to be overweight or obese (Tsai & Rosenheck, 2013; Tsemberis, Kent, & Respress, 2012). Housing First is an approach to place people who are chronically homeless into Permanent Supportive Housing (PSH) (Rog el at., 2014). There is clear evidence PSH programs increase housing retention and, reduce healthcare and criminal justice costs (Tsemberis & Eisenberg, 2014; McLaughlin, 2010). However, becoming housed does not necessarily improve a person’s overall quality of life (QOL) (Wolf et al., 2001). Improvement in diet and physical activity may be one way to improve QOL among vulnerable populations (Blissmer et al., 2006). However, this association has not been explored among PSH residents. The purpose of this study was to explore the patterns of change and relationship between diet, physical activity and QOL among PSH residents enrolled in a health coaching program. Method: We used data collected during baseline and follow up interviews from m.chat – a health coaching program for PSH residents in Fort Worth. The program utilizes motivational interviewing and wellness incentives to help people achieve health goals. Specifically, we examined demographic characteristics, diet, physical activity and overall QOL from 230 participants enrolled in the m.chat program. Paired t-test and mixed model analysis was performed utilizing SPSS software. Results: We found a significant improvement in the total QOL scores from baseline to follow-up. A random intercept model showed a positive association between change in diet and the improvement in QOL. Physical activity was not significantly related to improved QOL; however, there was large variation in the physical activity data. Conclusion: This study is the first to look at changes in QOL among PSH residents enrolled in a health coaching program. Interventions that encourage diet and physical activity may improve overall QOL among PSH residents.Item Non-Feminizing Estrogens Do Not Exhibit Antidepressant-Like Activity(2016-03-23) Prokai, Laszlo; Prokai-Tatrai, Katalin; Nguyen, VienShort description: In this exploratory lead compound evaluation, we aimed at addressing the utility of two non-feminizing estrogens, specifically 2-adamantyl-17β-estradiol (Ada-E2) and 2-adamantylestrone (Ada-E1), in a well-established animal model of depression-like behavior precipitated by estrogen deprivation. Purpose: To evaluate non-feminizing estrogens in fulfilling their overall premise for the treatment of climacteric symptoms. Methods: Mice were divided into six animals per treatment group. Test agents were dissolved either in corn oil vehicle or in 30% v/v aqueous 2-hydroxypropyl-β-cyclodextrin. The well-known antidepressant amitriptyline, as a reference standard, was used at 15 mg/kg dose, while the estrogen receptor (ER) antagonist fulvestrant was used at 4 mg/kg dose. The control groups received vehicle only. Test compounds in corn oil vehicle were administered subcutaneously (s.c.), while those in HPβCD were given intravenously (i.v.). Each group of animals was treated daily for five consecutive days injecting the test agents 100 µg/kg or 500 µg/kg doses on each day. Antidepressant-like activity were evaluated 30 min after the last injection using the Porsolt swim test (PST). The immobility time (in seconds, defined as the duration of floating motionless after the cessation of struggling and making only movements necessary to keep the head above the water) was recorded for 6 min simultaneously by a trained observer. Drug-likeness was evaluated via the online Osiris Property Explorer. Antioxidant potencies were determined experimentally by the ferric thiocyanate and thiobarbituric acid reactive substances methods. Results: Adding the bulky Ada to the already lipophilic E2 and E1 brought about further increase in the lipophilicity (logP) by [greater than] 2 log units. This increase was probably the most profound contributor to their unfavorable drug-likeness score. In agreement with our earlier quantitative structure–activity relationship study, our experimental assessment also supported that an increase in logP enhances antioxidant effect of estrogen-derived synthetic steroids and their analogs. However, while E2 and E1 did show significant reduction of immobility time in the mice PST, Ada-E2 and Ada-E1 failed to manifest activity in this paradigm (Immobility time is associated with depression-like behavior). Therefore, ERs play a pivotal role in triggering depression-like behavior in estrogen-deprived animals and non-feminizing estrogen offers no remedy for this symptom. Conclusions: Our lead evaluation has confirmed that both genomic and non-genomic mechanisms are required for broad-spectrum estrogen neuroprotection and treatment of menopausal symptoms. Therefore, non-feminizing estrogens such as Ada-E2 and Ada-E1 are not appropriate for the management of symptoms that manifest through ERs such as depression.Item Outcomes Following Modern Treatment for Osteosarcoma: The Cook Children's Experience(2016-03-23) Bowman, Paul; Shah, Deep; Konty, Logan; Jones, Garrett; Akers, Lauren; Kiel, Alice; Allen, JosephThe purpose of this study is to evaluate patient and tumor characteristics, treatments, and outcomes of patients at Cook Children’s Medical Center (CCMC) who were diagnosed with primary osteosarcoma from January 1, 1992 to December 31, 2013. Prior to the use of systemic chemotherapy, the survival rate for osteosarcoma patients was poor at 15-20% for two year survival. Current five year survival is more than 60% in non-metastatic disease with the addition of systemic chemotherapy. However, patients with metastatic disease at diagnosis have a lower 5 year survival of about 30%. This study will evaluate the outcomes of patients with osteosarcoma at CCMC relative to the outcomes noted at other institutions and in previous literature. It will also evaluate various potential prognostic factors to determine if they significantly affect patient outcomes. Researchers conducted a comprehensive retrospective chart review with the patients abstracted from the Cook Children’s Cancer Registry. The population consists of patients diagnosed with and treated for primary osteosarcoma at CCMC from 1992-2013. The 5 year overall survival for the population is 66.9% ± 6.1. The 5 year Event Free Survival for the population is 62.2% ± 6.6. The 5 year survival for patients with metastases at diagnosis is 50% ± 13.9. The 5 year survival for patients without metastases at diagnosis is 72.3 % ± 6.8. The 5 year survival of patients diagnosed from 1995 to 2003 is 70.0% ± 8.9. The 5 year survival for patients diagnosed from 2004 to 2013 is 64.2% ± 8.8. Survival rates for patients diagnosed with osteosarcoma at CCMC are consistent with the literature. Survival rates have not changed in the past 20 years for osteosarcoma.Item GRα and GRβ expression levels in trabecular meshwork determines steroid responsiveness upon glucocorticoid treatment(2016-03-23) Zode, Gulab; Mao, Weiming; Clark, Abbot; Patel, GaurangPurpose Glucocorticoid (GC) induced ocular hypertension (OHT) is a serious side effect of prolonged GC therapy with patients showing elevated intraocular pressure (IOP). Two major isoforms of glucocorticoid receptor (GRα and GRβ) regulate GCs sensitivity and specificity in various tissues. GRβ acts as a dominant negative regulator of GC activities and has been shown to regulate GC responsiveness in trabecular meshwork (TM). We evaluated GRα and GRβ expression levels in two mouse strains and studied how expression levels regulate GC and GC-induced OHT. Methods TM cells from C57BL/6J and BALB/cJ mice strains were isolated and characterized. RNA was isolated from TM cells and evaluated for GRα and GRβ expression levels using quantitative (Q)-PCR. To study how both TM cell lines respond to Dexamethasone (DEX) they were treated with DEX (100nM) and myocilin (MYOC) expression in TM cells was determined by Q-PCR analysis. Three month old C57BL/6J and BALB/cJ mice strains were used to evaluate changes in IOP upon DEX treatment. Mice were peri-ocularly injected with DEX-Acetate (100ug/eye) in both eyes. Conscious IOP measurements were taken using a TonoLab tonometer. Two-tailed Student’s t-test and One-way ANOVA were used for statistical analysis. Results MTM cells from both strains (C57BL/6J and BALB/cJ) expressed TM markers, including collagen IV, laminin and α-smooth muscle actin. GRα expression levels between both strains were similar. TM cells from BALB/cJ mice expressed significantly higher levels of GRβ compared to TM cells from C57BL/6J. When TM cells were treated with 100nM DEX, TM cells from C57BL/6J showed induction of myocilin expression compared to untreated controls whereas; TM cells from BALB/cJ did not show myocilin induction. IOP measurements upon DEX-Acetate treatment showed significant IOP elevation in C57BL/6J mice (ΔIOP of 3.5mmHg, p Conclusions In mouse, GRα and GRβ expression levels determines GC responsiveness. Higher GRβ expression levels leads to GC resistance. The current findings provide an important foundation for comparisons of GRα and GRβ expression levels in the TM among different strains. Also, manipulating GRα to GRβ expression levels holds a promise for desensitizing cells and tissues to GCs effects.Item Million Veteran Program (MVP)(2016-03-23) Rastogi, Padmashri; Reeves, Rustin; Bhat, Nikhil U.Purpose: The Million Veteran Program (MVP) is a national, voluntary research study conducted by the Department of Veterans Affairs Office of Research & Development. It is collaboration between the VA and veterans, whose goal is to illuminate potential links between genetic heterogeneity and disease. This is an important step in our scientific understanding about how genetic, as well as epigenetic makeup impinges upon disease characteristics and drug efficacy. Methods: Veterans who are treated in Veteran Affairs are eligible to participate. Those who provide consent are contacted by one of the researcher in the group. Veteran fills the survey related to their health and consent to give a blood sample. Central MVP biorepository saves the sample. Each sample is coded and so is their corresponding health information. Neither the person in the lab nor in the analysis knows the identity of the veteran. The key to the code is known to only a few personnel who are highly trained in research ethics thus safeguarding the privacy of the veterans. Results: Though the collection of data is ongoing, based on the analysis done so far, the correlation found between genetic and phenotypic pattern is helping to improve current treatment for certain cancers. Strong links that will very likely be found in this study, due to the large number of participating veterans (1 million), will be used to generate testable hypotheses for future study, such as if a particular gene polymorphism or epigenetic mark leads to a particular disease trait. This will enhance our understanding about how to better prevent and treat various diseases such as heart disease, diabetes, cancer, and post-traumatic stress disorder. Conclusions: Our site has contributed actively in the recruitment of veterans for this study by enrolling approximately 7000 veterans till now. With the help of research program, at our institution, we continue to work towards achieving our target. All over US, more than 450,000 patients have been enrolled in MVP. The research on the 400,000 samples has helped us discover a couple of useful drugs for cancer and schizophrenia. MVP aims to establish the largest of its kind database in the United States.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.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 HIV-1 TAT Induces MIR-132 Expression Leading to Neurotoxicity and Aberrant Dendritic Morphology(2016-03-23) He, Johnny; Rahimian, PejmanTITLE: HIV-1 Tat induces mir-132 expression leading to neurotoxicity and aberrant dendritic morphology Authors: Pejman Rahimian, Johnny He Presenter name: Pejman Rahimian Purpose: HIV-1 Tat is involved in the pruning of neurites and loss of synapses which are the most prominent pathological hallmarks of HIV-associated neurocognitive disorders (HAND). However the underlying molecular mechanisms of this synaptodendritic loss have not been elucidated. We report for the first time the induction of a brain-enriched microRNA by HIV-1 Tat protein leading to repression of significant regulating factors in dendritic arborization and synapse formation. Methods: Levels of miR-132 were quantitated in astrocyte cell lines (U373.MG), primary human and primary mouse astrocytes, and also in neurons (SH-SY5Y) following transfection with Tat plasmid and also in primary human astrocytes following infection with the VSVG-pseudotyped HIV-1 virus. Repression of miR-132 targets and involvement of CREB in miRNA induction were evaluated via Western blotting. Results: We observed significant miR-132 upregulation as the result of Tat expression in both neurons and astrocytes followed by the repression of miR-132 targets in both cell types. Activation of CREB as indicated by elevated p-CREB was observed along with Tat expression while using a Tat construct defective in CREB activation abrogated miR-132 induction by Tat. We also observed significant reduction in neuronal viability along with loss of dendritic arbor following Tat expression which correlate with the repression of miR-132 targets MecP2 and p250GAP and consequently BDNF loss. Conclusion: Our results indicate that HIV-1 Tat induces miR-132 in the brain through activation of CREB and stabilization of interaction between p-CREB and CREB-binding protein (CBP). Dysregulated miR-132 expression contributes to neurotoxicity and aberrant dendritic morphology witnessed in neurocognitive disorders associated with HIV-1 invasion of the central nervous system. Acknowledgments (ex. funding support, etc.) Neurobiology of Aging Training Grant-T32 AG020494 IACUC#: 2014/15-01-A04Item Gender Differences in Obstructive Sleep Apnea Treatment: A Retrospective Analysis(2016-03-23) Jouett, Noah; Watenpaugh, Donald; Smith, Michael PhD; Sanchez, AmaniIntroduction: Obstructive Sleep Apnea (OSA) affects four times as many men as women in the United States. However, nearly 5 million women have documented OSA, and there are likely many more due to historically high rates of OSA under-diagnosis. As a result of this documented gender difference, OSA treatment providers may not be sensitive to accommodate female patients undergoing positive airway pressure (PAP) therapy, which is the gold standard for OSA treatment and is notoriously obtrusive and uncomfortable. We hypothesized in a retrospective analysis of OSA patient records that (1) PAP treatment is less effective in women vs. men and (2) that women have lower compliance rates to PAP treatment than men. Methods: The University of North Texas Health Science Center Institutional Review Board approved this study. We studied the records of 619 patients (43% women, 57% men). Diagnosis of OSA was established by full night polysomnography (PSG) according to American Academy of Sleep Medicine (AASM) criteria. For this study, only patients prescribed for PAP machines that provide usage data, estimated apnea-hypopnea indices (AHIs), air leakage rates, recent detailed night-to-night data, and (if automated) mean and range of treatment pressures were considered. PAP data was downloaded from each patient’s machine during their office visit (see below) and was transferred into a database. Chi-square analysis assessed for gender differences in YFU vs. OFU treatment groups. Results: In comparing men and women and effectiveness of PAP treatment, there was a greater reduction in respiratory events in men than in women (P=0.037). Men initially had a greater number of baseline events, (P= Conclusions: The results indicate that PAP usage is substantially less in women compared to men, both in terms of 5 of sleep time and days/week, and women receive slightly less benefit from PAP use versus men. Furthermore, We contend that because women use PAP treatment less than men, they are more likely to receive inadequate treatment for their OSA.Item Development of a Visualization Tool to Understand Gait(2016-03-23) Patterson, Rita; Le, DavidObjective: The aim of this study was to create a visualization tool that illustrates the motion of specific joint angles during gait cycles. An example of how this tool would be beneficial to understanding gait will be presented by comparing a patient’s joint angle before and after application of Osteopathic manipulative medicine (OMM) and heel lift therapy to improve back pain. Design: A V-gait CAREN system was used to create realistic virtual environments in order to test functional gait and balance in situations that resemble real life. Reflective markers were placed on the head, arms, legs and torso. A 12-camera Motion Analysis System (Motion Analysis Corp., Santa Rosa, CA) tracked reflective markers placed on the body, allowing precise calculation of kinematics, gait parameters, and joint range of motion during movements using the GRAIL (Gait Real-Time Analysis interactive lab) and GOAT (Grail offline analysis tool). A list of 17 joint parameters were compiled and separated into left and right joints on an excel sheet. For each parameter, 50 cycles of gait were analyzed. Sample data from a preliminary subject that has gone through gait analysis via the V-gait CAREN system (Computer Assisted Rehabilitation Environment Network, Motek Medical, The Netherlands) were inputted into the list and each cycle was graphed Results: Graphs for joint parameters up to 50 gaits cycles were automatically generated using the excel tool and proved to be effective for visualizing gait motion. Conclusions: Presentation of one possible way to utilize this tool looks at data from one of our existing studies that compares gait changes of a patient before and after OMM and heel lift therapy to investigate improvements in back pain. Other potential uses for this tool that is not presented would be to visualize the motion of specific joints and compare a subject with a pathologic joint to a subject with a non-pathologic joint. In addition, left and right side joint angles could be compared within one subject. Lastly, pre-treatment and post-treatment analysis can be done for patients using this tool.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.