• GERIATRIC ASSESSMENT VARIABLES ADD PROGNOSTIC VALUE TO THE INTERNATIONAL PROGNOSTIC SCORING SYSTEM FOR MYELODYSPLASTIC SYNDROME

      Fegas, Rebecca K.; The University of Arizona College of Medicine - Phoenix; Driver, Jane (The University of Arizona., 2015-04-10)
      Background: The International Prognostic Scoring System (IPSS) for myelodysplastic syndrome (MDS) is commonly used to predict survival and assign treatment. We explored whether markers of frailty add prognostic information to the IPSS in a cohort of older patients. Design, Setting, Participants: Retrospective cohort study of 114 MDS patients ≥ age 65 who presented to Dana‐Farber Cancer Institute between 2006‐2011 and completed a baseline quality of life questionnaire. Measurements: We evaluated questions corresponding to frailty and extracted clinical‐ pathologic data from medical records. We used Kaplan‐Meier and Cox proportional hazards models to estimate survival. Results: 114 patients consented and were available for analysis. The median age was 72.5 years, and the majority of patients were white ( 94.7%), male ( 74.6%), and over half had a Charlson comorbidity score < 2. Few patients ( 23.7%) had an IPSS score consistent with low‐risk disease and the majority received chemotherapy. In addition to traditional prognostic factors (IPSS score and history of prior chemotherapy or radiation), significant univariate predictors of survival included low serum albumin, Charlson score, the ability to take a long walk, and interference of physical symptoms in family life. The multivariate model that best predicted mortality included low serum albumin (HR=2.3; 95%CI: 1.06‐5.14), previous chemotherapy or radiation (HR=2.1; 95%CI: 1.16‐4.24), IPSS score (HR=1.7; 95%CI: 1.14‐2.49), and ease taking a long walk (HR=0.44; 95%CI: 0.23‐0.90). Conclusions: In this study of older adults with MDS, we found that markers of nutritional status and self‐reported physical function added important prognostic information to the IPSS score. More comprehensive risk assessment tools for older patients with MDS that include markers of function and frailty are needed.
    • IDENTIFYING A POSSIBLE LINK BETWEEN ECTOPIC GERMINAL CENTERS AND THE EVOLUTION OF TYPE I DIABETES

      Alcantar, Eduardo C. Jr.; The University of Arizona College of Medicine - Phoenix; Wen, Li (The University of Arizona., 2015-04)
      The multifaceted phenotype of the B‐lymphocyte has a remarkably effective role in peptide derived pathogen clearance and the prevention of re‐infection. This mechanism of host tolerant defense can be attributed to the actions of particular cellular subsets that arise from Blymphocytes: memory cells and high‐affinity antibody secreting plasma cells. Notably B cell propagation does not commence without the help of follicular helper T cells (TFH), a specialized subset of CD4+ cells. TFH cells are involved in the maturation and differentiation of Blymphocytes after antigen stimulation with a thymus‐dependent peptide. With this specific stimulus the formation of germinal centers (GCs) within B‐cell follicles of secondary lymphoid organs is induced and it is within these centers that TFH cells are able to interact with B cells to facilitate immunoglobulin affinity maturation, somatic hypermutation, and isotype class switching. Importantly, these respective processes play a fundamental role in manufacturing high‐affinity antibodies for effective pathogen clearance. Conversely, by means not well understood, the occurrence of spontaneous GC formation and the mass production of high affinity autoreactive antibodies have been shown to occur simultaneously with the development of autoimmune diseases. By the same token this incident is of particular interest and could play a role in the destruction of pancreatic insulin secreting β cells consequently driving the pathogenesis of type I diabetes. Our objective is to identify a possible correlation between the evolution of type I diabetes and the proliferatory behavior of B‐lymphocytes and TFH cells within developing GCs of non‐obese diabetic (NOD) mouse models.
    • IMPROVING THE DETECTION OF HYPERTENSION IN PEDIATRIC AMBULATORY VISITS

      Wheeler, Kellie; The University of Arizona College of Medicine - Phoenix; Panchanathan, Sarada Soumya (The University of Arizona., 2015-04)
      Background and Significance The prevalence of pediatric hypertension (HTN) has increased in the past several decades and is projected to continue to rise.2 Because normal blood pressure (BP) values in children depend on age, sex, and height, HTN is difficult to recognize. If not diagnosed during childhood, HTN poses several long‐term health risks.4,10 Electronic medical records (EMR) have tools to help recognize elevated BP in children. Unfortunately, many clinicians are unaware of these support tools, and pediatric HTN is underdiagnosed. Research Question This study is designed to improve the detection of HTN in children. Methods This is a prospective quality improvement (QI) study completed at a teaching institution with rotating physicians. We reviewed the charts of 1697 children aged 3 to 18 years who were seen by physicians for well‐child visits in March, June, July, August, November 2014, and January 2015. We recorded children with elevated BP and determined if HTN was recognized (noted in the assessment/plan or BP repeated). We used March as our baseline detection rate and completed five interventions, one before each month. All interventions consisted of PowerPoint presentations for medical personnel (physicians, nurses, medical assistants). The last two interventions consisted of a change in the EMR (BP percentiles displayed in a summary page) and signs hung in the clinic. Pre‐ and post‐intervention data underwent analysis, and we examined factors that may impact early detection of HTN. Results Of the 1697 children, 188 (11.1%) had elevated BP. The prevalence of elevated BP declined from the pre‐intervention month to post‐intervention months (March 13.5%, June 10.3%, July 9.7%, August 9.2%, November 12.5%). The prevalence returned to baseline by January (13.5%). The recognition of elevated BP improved from 25% in March to 44% and 55% in June and July, respectively. There was a decline in detection from July to August and November (55% to 41% and 35%). There was improved detection again from November to January (35% to 48%). Factors that increased the detection of HTN were obesity (χ2=22.9, p=0.000002), systolic BP >120 (χ2=8.1, p=0.0045), and a past history of elevated BP (χ2=5.1, p=0.024). Conclusions Our educational interventions improved the absolute detection of HTN. Repetition of interventions and involvement of the whole care team were important for sustaining the improvements, especially for a teaching institution with rotating physicians. Repeated interventions may not be necessary for private practice clinics. The improved detection correlated with a steady decline in the prevalence of HTN, probably related to blood pressures that were falsely elevated due to patient anxiety and incorrect cuff sizing. Obesity, systolic BP>120, and past history of at least one elevated BP significantly improved the detection. This QI project was not intended to determine the efficacy of each intervention, but rather to improve the detection rate as a whole. We cannot conclude whether the monthly changes were due to chance, but we can conclude that we improved the overall detection.
    • INTERCHANGEABILITY OF THE I‐STAT POINT OF CARE ANALYZER WITH CENTRAL LABORATORY TESTING IN AN EMERGENCY DEPARTMENT SETTING

      Little, Colin; The University of Arizona College of Medicine - Phoenix; Sarko, John (The University of Arizona., 2015-04-10)
      Background and Significance: The i‐STAT point of care blood analyzer is a handheld device used for a variety of laboratory analyses in medical settings. Much research has been performed to evaluate its validity, but it has not been exhaustively tested in real‐world emergency department settings, despite its increasingly popular use in such settings. Methods: We retrospectively examined medical records at the Maricopa Integrated Health Systems Emergency Department to find 100 instances between February 2014 and September 2014 in which a patient had electrolyte testing performed on both the i‐STAT and in the central laboratory within a 60 minute timeframe. These data were examined using variance of means and Bland‐Altman graphing for equivalency. Results: We set the clinical equivalence threshold for each lab to be 5% of the mean normal value. That is, if the i‐STAT differed from central lab by less than 5% of the middle of the normal range (137‐145 for sodium, 5% of which is 7) then we consider them to be clinically equivalent. At this level we were unable to show clinical equivalence. In additional, all electrolytes tested showed small but significant bias between the i‐STAT and the central laboratory. Re‐examination of the data excluding all measurements more than 15 minutes apart showed similar findings. Conclusions: At this time we cannot show equivalency between the i‐STAT device and the central laboratory when used under real‐life emergency department conditions. More research is needed is to support or refute these findings.
    • LONGITUDINAL ASSESSMENT OF END‐OF‐LIFE DECISIONS BY MEDICAL STUDENTS, RESIDENTS AND ATTENDINGS FOR PEDIATRIC CASES

      Sinha, Natasha; The University of Arizona College of Medicine - Phoenix; Beyda, David (The University of Arizona., 2015-04-14)
      End‐of‐life (EOL) care and decision‐making in pediatrics is a challenging and complex aspect of patient care experienced by residents and physician attendings. Previous studies have evaluated determinants that contribute to physicians’ attitudes towards EOL care as well as preparedness of students and residents in EOL decision‐making. However, the determinants contributing to a physician’s ability to make such decisions and feel confident in addressing EOL issues are dynamic. Recognizing that decision‐making changes over time, identifying when these changes occur may demonstrate the need for educational interventions for medical students and residents early in their career to help prepare them for EOL decision‐making. A longitudinal assessment of changes in attitudes and knowledge of EOL discussions and how they impact EOL decision‐making was not previously evaluated. This preliminary study establishes a baseline for medical student, resident, and attendings for EOL decision‐making and those factors that contribute to their decisions. This preliminary data has demonstrated a difference amongst attendings compared to residents and students. Despite low probability of survival, residents and students are more likely to select more aggressive management options when compared to attendings. Data obtained after completion of future surveys will show when decision‐making changes, which factors contribute to these changes and their significance in making decisions, and when participants are comfortable addressing EOL care.
    • MEDICAL STUDENTS’ KNOWLEDGE AND OPINIONS OF THE AFFORDABLE CARE ACT AND OTHER HEALTH CARE POLICY ISSUES

      Donovan, Derek; The University of Arizona College of Medicine - Phoenix; Winkelman, Tyler; McEchron, Matthew (The University of Arizona., 2015-04-10)
      Since the Affordable Care Act (ACA) was signed into law in March of 2010, there have been multiple large survey studies focusing on physicians’ thoughts towards health care policy issues. 1‐6 Unfortunately, there has not been adequate attention paid to medical students’ feelings on reform in the literature. Today’s medical students will enter their practice at a vital time in the ACA’s implementation and will play an integral role in health care reform throughout their careers.7,8 This study is a national project that used a survey tool to demonstrate how well medical students know the details of the ACA and what their feelings are on the legislation. The survey was sent to eight different medical institutions across the country with ten total medical school campuses, using SurveyMonkey to collect results. The institutions were chosen based on their geographic location, mix between private and public institutions, and available investigators at each institution. The survey tool was developed by Tyler Winkelman, MD, from the University of Minnesota after a comprehensive literature review, adaptation of items from his previous survey of medical students in Minnesota performed in 2012, and consultation with physicians and policy experts.9 The survey focuses on student’s opinion of the ACA, knowledge of nine key provisions in the ACA, level of support of key health care policies, feelings towards health care policy education in medical schools, and socio‐demographic information, including political ideology, debt amount and intended specialty. Data analysis was performed using Pearson’s Chi‐square tests and multiple logistic regression models at The University of Minnesota to test for associations between students’ opinion of the ACA and five key predictors: debt, medical school year, political ideology, ACA knowledge, and intended specialty. A total of 2,761 out of 5,340 medical students (52%) responded to the survey, with 63% of students indicating support for the ACA, 75% agreeing that they understand the key ACA provisions, and 56% indicating professional obligation to assist in implementation of the ACA. Students intending to enter surgery or a surgical subspecialty and students who identified themselves as conservative were found to have less support and professional obligation of the ACA when compared to students entering primary care (Internal medicine, family medicine, pediatrics, internal medicine/pediatrics, or emergency medicine) or identifying themselves as liberal or moderate. Students that were most knowledgeable of the ACA were found to more likely support the ACA and indicate professional obligation towards the legislation. In conclusion, our study found that the majority of medical students indicate support for the ACA and feel they have a professional obligation in assisting implementation. The views of the ACA differ based on student’s political ideology, anticipated specialty, and knowledge of key ACA provisions, but overall, there is optimism that this high level of support can lead to advocacy and successful health care reform down the road.
    • PEDIATRIC PAIN ASSESSMENT PRACTICES AND PREFERENCES OF EMS PROVIDERS

      Parrish, Ashley; The University of Arizona College of Medicine - Phoenix; Bulloch, Blake (The University of Arizona., 2015-04-13)
      Background: Pain scales developed for children were noted not to be useful or practical in an ambulance, and EMS providers have been found to use non‐standardized measures of pain severity in children. A recently published evidence‐based guideline recommends using pictorial scales (PS) for patients aged 4‐12 years, and observational‐behavioral scales (OBS) for younger patients. Objectives were to assess EMS providers’ baseline knowledge, self‐reported practices, self‐efficacy for treating pain in children, and preference for pediatric pain scales. Methods: A survey and education module were administered to a convenience sample of EMS providers from four agencies within a large metropolitan area. Providers answered 20 Likert scale items, received a 15‐minute didactic on pain assessment in children, and then answered four additional survey items. Results: There were 397 surveys returned (80% of providers receiving didactic). Six‐tenths of providers had practiced >10 years, 99% were EMT‐P, and 91% were male. 88% reported feeling “Very‐Extremely” comfortable measuring pain severity in adults; 38% reported the same in children. 57% reported having been trained on the use of pain scales in children; 46% were at least “Moderately” familiar with any PS and 24% with any OBS. While 44% assessed their current practice as “Sometimes‐Always” using pediatric scales, <25% of providers reported carrying paper or electronic copies of pain scales. 75% reported using their own observation to assess pain “Most of the Time‐Always.” Self‐efficacy results for utilizing pain protocols and measuring pain scores for 8‐year and 36‐month patients revealed 68% and 48% were at least “Mostly” certain they could perform correctly. After education about pediatric pain scales, 41% and 31% reported they would be more than “Somewhat” likely to use PS or OBS, respectively. Conclusion: A sample of EMS providers reported a high level of discomfort assessing pain in children, a moderate prevalence of training, and a low familiarity with existing pediatric pain scales. Most use general impression to assess pain instead of pain scales. After education, the minority of providers reported likelihood of incorporating these tools into their practice. This is an important barrier to adoption of the evidence‐based guideline for management of acute traumatic pain.
    • PILOT STUDY: A NOVEL APPROACH TO CASE‐BASED INSTRUCTION OF MEDICAL STUDENTS USING SIMULATION EDUCATION

      Jugler, Tanner; The University of Arizona College of Medicine - Phoenix; Hartmark-Hill, Jennifer (The University of Arizona., 2015-04-10)
      This pilot project explores medical student preference regarding simulation education in case based instruction (CBI) compared with the traditional Power Point lecture CBI. The study population consisted of volunteer first, second, third, and fourth year medical students. The subjects were randomized into control (traditional CBI) and intervention (simulation CBI) groups and preference data was collected via pre‐ and post‐survey administered before and after the activity. Preference was limited to enjoyment of learning activity and opinion of benefit on exams of the learning activity. T‐tests were applied to the data in order to determine statistical significance. Enjoyment of the simulation activity was determined to be higher post‐simulation activity in the intervention group compared to the control group. While opinion that simulation CBI may be beneficial in regard to exam scores and knowledge retention was above neutral for the two groups, this study did not determine a significance in opinion between the control and intervention groups. The study results suggest that students who have experienced a simulation CBI enjoy them more compared to the traditional CBI and are more in favor of changing the current model of case‐based instruction.
    • THE POTENTIAL FOR MORAL HAZARD IN AN ALLOPATHIC INTERVIEW SETTING

      Reeder, David; The University of Arizona College of Medicine - Phoenix; Beyda, David (The University of Arizona., 2015-04-13)
      The value of an allopathic medical school interview lies in its inherent ability to produce something of value that is unobtainable by other means: a rough assessment of the non‐ cognitive components of a viable candidate. Many allopathic institutions rely on the interview when determining applicant viability for both professional standards and institutional fit. However, applicants can distort the truth or train themselves to appear to exude any one of a number of admirable qualities for a brief period of time. Responses that reflect socially acceptable answers, rather than the true nature of an applicant’s character, represent forms of dishonesty. It is our belief that the high‐stakes setting of a conventional allopathic interview creates a moral hazard for prospective matriculates, such that applicants’ genuine responses are confounded with social desirability bias. Social desirability is often simplified for the research world to refer to the articulation of both self‐deceptive enhancement and impression management (IM). We sought to establish the presence of impression management and/or self‐deceptive enhancement tactics among interviewing allopathic medical school applicants. The presence of the aforementioned was determined using the 6th version of the Balanced Inventory of Desirable Responding (BIDR), a validated inventory that relies on 40 self‐responses on a Likert scale to common situations. We offered the BIDR interview to all interviewing applicants to the University of Arizona College of Medicine ‐ Phoenix on three of the six interview days. This inventory was administered during a 10 minute break period offered directly after the completion of the university’s multiple mini interviews, so as to assess the presence or absence of social desirability as close to the high stakes setting as possible. We received 104 responses, 12 of which were not included in the dichotomous scoring because they were not completed in their entirety. Our findings from 92 allopathic medical school applicant respondents indicated that our average interviewing medical school applicant was engaging in impression management tactics above and beyond the oft‐referenced BIDR cutoff values, with an average of 7.543/20; however, they were not engaging in self‐deceptive enhancement tactics beyond their BIDR reference peers with an average of 6.27/20. Both self‐ deception and impression management exist on a spectrum; however the arbitrary cutoffs of honest impression management established by Paulhaus’ 6th version of the BIDR were exceeded. Our results indicate that the context of allopathic interviews is associated with increased levels of impression management tactics; conversely, it is not associated with increased self‐deceptive enhancement tactics.
    • THE RELATIONSHIP OF PLAQUES, TANGLES, AND LEWY‐TYPE ALPHA‐SYNUCLEINOPATHY TO VISUAL HALLUCINATIONS IN PARKINSON’S DISEASE AND ALZHEIMER’S DISEASE

      Morshed, Trisha; The University of Arizona College of Medicine - Phoenix; Jacobson, Sandra (The University of Arizona., 2015-04-13)
      Objective: Formed visual hallucinations are a common phenomenon in neurodegenerative disorders such as Parkinson’s Disease (PD), Alzheimer’s disease (AD) and Dementia with Lewy bodies (DLB). While Lewy‐type alpha‐synucleinopathy (LTSis the hallmark neuropathological finding in PD and DLB, amyloid plaques and neurofibrillary tangles are the pathological finding in AD. Previous research has linked complex or formed visual hallucinations (VH) to LTS in neocortical and limbic areas in patients with PD and DLB. As VH also occur in Alzheimer’s disease, and AD pathology often co‐occurs with LTS, we questioned whether this pathology might also be linked to VH. Methods: We performed a semi‐quantitative neuropathological study across brainstem, limbic, and cortical structures in subjects with a documented clinical history of VH and a clinicopathological diagnosis of Parkinson’s disease (PD), Alzheimer’s disease (AD), or dementia with Lewy bodies (DLB). 173 subjects – including 50 with VH and 123 without VH – were selected from the Arizona Study of Aging and Neurodegenerative Disorders. Clinical variables examined included the Mini‐mental State Exam, Hoehn & Yahr stage, and total dopaminergic medication dose. Neuropathological variables examined included total and regional LTS and plaque and tangle densities. Results: A significant relationship was found between the density of LTS and the presence of VH in all diagnostic groups. Plaque and tangle densities also were associated with VH in PD (p=.003 for plaque and p=.004 for tangles), but not in AD, where densities were high regardless of the presence of hallucinations.. Conclusion: Plaques and tangles as well as LTS may contribute to the pathogenesis of VH. Incident VH may be a clinical indicator of underlying pathological events: the development of plaques and tangles in patients with PD, and LTS in patients with AD.
    • RESCUE ECHOCARDIOGRAPHIC FINDINGS ARE DIFFERENT BASED ON PATIENT SETTING

      Vanhoy,Steven; The University of Arizona College of Medicine - Phoenix; Hopf, Harriet (The University of Arizona., 2015-04-14)
      Objective: To compare findings of emergency echocardiography (rescue echo) in the intra‐ operative period to findings of rescue echo in the ICU setting. Design: We queried a database of perioperative echo for all rescue echo studies done over a two year period. We compared the frequency of left ventricular (LV) and right ventricular (RV) systolic dysfunction, LV diastolic dysfunction, LV segmental wall motion abnormalities, and hypovolemia of the intraoperative and ICU studies. Results: LV and RV systolic dysfunction were more prevalent in ICU rescue echo studies compared to intra‐op rescue studies (22% vs. 10%, and 34% vs. 13%, respectively, p<0.05 for each). LV diastolic dysfunction was more prevalent in ICU rescue echo studies compared to intra‐op rescue studies (60% vs. 48%, p<0.05). Segmental wall motion abnormalities (SWMA) were more prevalent in the ICU compared to intra‐op setting (38% vs. 19%, p<0.05). Conclusion: In an observational study of real‐world rescue echo, the incidence of LV and RV systolic dysfunction, LV diastolic dysfunction, and LV SWMA were all more common in the ICU compared to the intra‐op studies. This could reflect the differences in patient population, differences in reasons clinicians perform rescue echo in the OR and in the ICU, or the hemodynamic effects of anesthesia.
    • THE ROLE OF TURMERIC AS AN ADJUVANT THERAPEUTIC FOR OSTEOLYTIC BREAST CANCER BONE METASTASES

      Lukefahr, Ashley Leigh; The University of Arizona College of Medicine - Phoenix; Funk, Janet (The University of Arizona., 2015-04-13)
      Zoledronic acid (ZA), the gold standard treatment for breast cancer‐derived osteolytic bone lesions, induces apoptosis in mature osteoclasts. Curcumin, a plant‐dervied component of turmeric (Curcuma longa), inhibits osteoclast differentiation. This study aimed to determine the in vitro and in vivo effects of ZA and curcuminoids, alone and combined, on osteoclast differentiation and survival, breast cancer cell growth, breast cancer cell‐induced osteolytic bone lesion area, and bone mineral density (BMD). Curcuminoids, but not ZA, inhibited osteoclast formation at doses that did not alter precursor viability, as assessed by osteoclastogenesis assays using murine RAW 264.7 cells. Combined curcuminoids and ZA did not differ from curcuminoids alone in their effects on osteoclast survival/formation. The half maximal inhibitory concentration (IC50) for ZA alone was 4 μM, while the IC50 for curcuminoids plus ZA was 6μM. Curcuminoids and ZA inhibit in vitro cell viability of human breast cancer‐ derived MDA‐MB‐231 cells, as assessed by MTT assays. The IC50 of ZA alone was projected to be 1.0677 x 10^4 μM, while the IC50 for curcuminoids alone (9.1 x 10^1 μM), was close to the IC50 for curcuminoids plus ZA (1.31 x 10^2 μM curcuminoids with 300 μM ZA). In vivo effects of ZA (2 μg/kg/d) and curcuminoids (25 mg/kg/d), alone and combined, on osteolytic bone lesions dervied from innoculation with MDA‐MB‐231 cells were assessed. Radiographically‐evident osteolytic bone lesion area did not differ between treatment groups, with a trend towards decreased osteolytic lesion area in mice treated with ZA. BMD In non‐responders, without bone or pericardiac tumors, assessed by dual energy x‐ray absorptiometry, was increased in mice administered ZA. Thus, for the first time, the combined in vitro effects of ZA and curcuminoids on osteclast formation and survival were demonstrated, as well as the combined effects of ZA and curcuminoids on bresat cancer‐derived osteolytic bone lesions and BMD.
    • TRENDS IN CHLAMYDIA TRACHOMATIS INFECTION IN MARICOPA COUNTY ADOLESCENTS, 2006‐2010

      Breslauer, Cori Ann; The University of Arizona College of Medicine - Phoenix; Mickey, Tom; Taylor, Melanie (The University of Arizona., 2015-04)
    • THE TWEAK-FN14 LIGAND RECEPTOR AXIS PROMOTES GLIOBLASTOMA CELL INVASION AND SURVIVAL VIA ACTIVATION OF MULTIPLE GEF-RHO GTPASE SIGNALING SYSTEMS

      Fortin Ensign, Shannon Patricia; The University of Arizona College of Medicine - Phoenix; Tran, Nhan (The University of Arizona., 2015-04-10)
      Glioblastoma (GB) is the highest grade and most common form of primary adult brain tumors, characterized by a highly invasive cell population. GB tumors develop treatment resistance and ultimately recur; the median survival is nearly fifteen months and importantly, the invading cell population is attributed with having a decreased sensitivity to therapeutics. Thus, there remains a necessity to identify the genetic and signaling mechanisms that promote tumor spread and therapeutic resistance in order to develop new targeted treatment strategies to combat this rapidly progressive disease. TWEAK-Fn14 ligand-receptor signaling is one mechanism in GB that promotes cell invasiveness and survival, and is dependent upon the activity of multiple Rho GTPases including Rac1. Here, we show that Cdc42 is essential in Fn14-mediated Rac1 activation. We identified two guanine nucleotide exchange factors (GEFs), Ect2 and Trio, involved in the TWEAK-induced activation of Cdc42 and Rac1, respectively, as well as in the subsequent TWEAK-Fn14 directed glioma cell migration and invasion. In addition, we characterized the role of SGEF in promoting Fn14-induced Rac1 activation. SGEF, a RhoG-specific GEF, is overexpressed in GB tumors and promotes TWEAK- Fn14-mediated glioma invasion. Moreover, we characterized the correlation between SGEF expression and TMZ resistance, and defined a role for SGEF in promoting the survival of glioma cells. SGEF mRNA and protein expression are regulated by the TWEAK-Fn14 signaling axis in an NF-B dependent manner and inhibition of SGEF expression sensitizes glioma cells to TMZ treatment. Lastly, gene expression analysis of SGEF depleted GB cells revealed altered expression of a network of DNA repair and survival genes. Thus TWEAK-Fn14 signaling through the GEF-Rho GTPase systems which include the Ect2, Trio, and SGEF activation of Cdc42 and/or Rac1 presents a pathway of attractive drug targets in glioma therapy, and SGEF signaling represents a novel target in the setting of TMZ refractory, invasive GB cells.
    • VARIABLES IMPACTING DENGUE SURVEILLANCE IN KEY WEST FLORIDA

      Raza, Ali; The University of Arizona College of Medicine - Phoenix; Ernst, Kacey (The University of Arizona., 2015-04-13)
      Background: Dengue fever is the most common mosquito borne viral disease in the world. Its symptoms can be fairly nonspecific and most commonly include fever, rash, headache, and eye pain. Passive surveillance is currently the most prevalent method used to detect dengue cases in the United States. Identification of positive cases can be limited by the public’s awareness of the disease’s symptoms, barriers to healthcare seeking behavior, and by physician approval of laboratory testing. Objective: This study sought to evaluate barriers to dengue reporting, as well as the patient‐ level factors that may limit the efficacy of passive surveillance of dengue in Key West, Florida. Methods: Cross‐sectional surveys were administered across Key West, FL. Subjects were asked if they had a recent fever, additional dengue symptoms, and whether they sought medical care for these symptoms. Also the hypothetical question was posed: would you seek medical care for a fever greater than 102 F? Responses were stratified according to patient characteristics and demographics. Results: In Key West, patient‐level factors that influenced the decision to seek medical care for a high fever were: having a specific doctor call when sick (p<0.006), health insurance status (p<0.037), and ethnicity (p<0.005). Additionally, barriers to dengue reporting were identified. The most impactful were the decision to seek medical care for symptoms consistent with dengue fever, and the doctor’s decision to administer confirmatory dengue laboratory tests. Only one person with a recent fever plus one additional classic dengue symptom received laboratory testing, and this was done outside of the United States. There were four individuals who met the current WHO clinical case definition for dengue, yet none were offered laboratory testing or were diagnosed with the disease. Conclusion: This study shows that both patients and doctors in Key West, Florida underestimate the potential for dengue when there are symptoms consistent with the disease. As such, it is certainly possible that there have been unreported cases in the country.
    • WATCHFUL WAITING: DEFERRED LADD PROCEDURE IN PATIENTS WITH CONGENITAL HEART DISEASE, HETEROTAXY SYNDROME, AND KNOWN INTESTINAL MALROTATION

      Wadas, Erica; The University of Arizona College of Medicine - Phoenix; Graziano, Kathleen; Nigro, John (The University of Arizona., 2015-04-14)
      Purpose: Infants born with Heterotaxy Syndrome (HS) often have intestinal malrotation in addition to severe congenital heart disease (CHD). Given the catastrophic risk of midgut volvulus, where the vascular supply to the gut is cut off causing necrotic bowel and possible future short‐gut syndrome following surgery, an elective Ladd procedure is recommended at the first diagnosis of malrotation. In patients with severe CHD, however, the risk of complications from prophylactic surgery is high, especially in infancy prior to stable cardiac palliation. This study sought to determine whether deferring a Ladd procedure during the first six months of life in infants with CHD is safe by focusing on the incidence of volvulus in the HS population, morbidity of volvulus and morbidity of an elective Ladd procedure. Methods: Medical records of patients with HS and intestinal malrotation at Phoenix Children’s Hospital from 2006‐2011 were reviewed. Stage of heart surgery, severity of heart disease, diagnosis of intestinal malrotation, and timing of Ladd procedure if applicable were recorded. Results: 31 patients with HS and intestinal malrotation were identified. Of the 31, 9 had a Ladd procedure prior to six months of age, 2 for volvulus and the other 7 either electively or for less severe GI symptoms that were not suggestive of volvulus. The other 22 did not have a Ladd procedure prior to six months of age. There was one death (1/22) from a non‐gastrointestinal cause in a patient who had not undergone a Ladd procedure. There were no deaths in the 9 patients who underwent a Ladd procedure (0/9). Conclusions: Given the low overall incidence of volvulus in HS, and with continued vigilance for obstructive symptoms, this study suggests that delaying the Ladd procedure in asymptomatic patients with HS and CHD and intestinal malrotation is safe. Watchful waiting may reduce the incidence of cardiac complications during the Ladd procedure by allowing for stabilizing cardiac surgical palliation prior to elective abdominal surgery.
    • “WATCHING” WHAT WE EAT: WHAT TELEVISION IS MODELING

      Cavallo, Katherine; The University of Arizona College of Medicine - Phoenix; Coles, Sarah (The University of Arizona., 2015-04-09)
      Background: Obesity has transitioned from an individual health concern to being a national problem with almost two‐thirds of the adult population in the United States now overweight or obese1. Television potentially provides a medium in which to model healthy and unhealthy behaviors to millions of viewers each week. Although there is no quick solution to obesity, promoting and normalizing healthy lifestyles in today’s most viewed shows may be one tool to help combat an obesogenic lifestyle. Research Question: To what degree do today’s most popular sitcoms model healthy and unhealthy behaviors? Methods: A scorecard with 11 behaviors (6 healthy and 5 unhealthy) was created using publically published guidelines from the Center for Disease Control (CDC)1,2,3, World Health Organization (WHO)4, and the United States Department of Agriculture (USDA)5,6. The top three sitcoms for the 2013‐2014 season, as determined by TV Guide, were viewed and analyzed by one evaluator. These included The Big Bang Theory, The Millers, and Modern Family7. Results: In total, 898 unhealthy behaviors and 532 healthy behaviors were portrayed. The Big Bang Theory demonstrated the most behaviors overall and had the most favorable ratio of healthy to unhealthy behaviors at 1/1.1, compared to 1/3.8 for The Millers and 1/3.2 for Modern Family. The most common unhealthy behavior viewed was beverage choice with 492 occurrences. One of the least portrayed healthy behaviors was moderate physical activity with only 47 instances. In two of the three shows, there were remarkably few examples of fruit and vegetable consumption. Conclusion: Today’s top three sitcoms expose their viewers to many healthy and unhealthy behaviors during the span of a 22‐minute show. Significantly more unhealthy behaviors were portrayed than healthy behaviors. The most common unhealthy behavior centered on beverage choice. This is a behavior that can easily be adjusted to promote a healthier lifestyle. Additionally, food content could reflect more healthy choices. Television shows reach millions of viewers each week and may prove to be a useful tool in helping to reinforce and normalize healthy lifestyle choices.