IUPUI Research Day 2013

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A program book describing the Research Day 2013 events and posters is available from: http://hdl.handle.net/1805/4914.

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    Paced Respiration for Vasomotor and Other Menopausal Symptoms: A Randomized, Controlled Trial
    (Office of the Vice Chancellor for Research, 2013-04-05) Carpenter, Janet S.; Burns, Debra S.; Wu, Jingwei; Otte, Julie L.; Yu, Menggang
    Background: Paced respiration has been internationally recommended for vasomotor symptoms (e.g., hot flashes, night sweats) despite limited empirical evidence. Objective: To evaluate efficacy of a paced respiration intervention against breathing control and usual care control for vasomotor and other menopausal symptoms. Design: A 16-week, 3-group, partially blinded, controlled trial with 2:2:1 randomization and stratification by group (breast cancer, no cancer) was conducted in a Midwestern city and surrounding area. Participants: 218 randomized women (96 breast cancer survivors, 122 menopausal women without cancer) were recruited through community mailings and registries (29% minority). Interventions: Training, home practice support, and instructions to use the breathing at the time of each hot flash were delivered via compact disc with printed booklet (paced respiration intervention) or digital videodisc with printed booklet (fast shallow breathing control). Usual care control received a letter regarding group assignment. Main Measures: Outcomes included hot flash frequency, severity, and bother (primary), hot flash interference in daily life, perceived control over hot flashes, and mood and sleep disturbances (secondary). Intervention performance, adherence, and adverse events were assessed. Key Results: There were no significant group differences for primary outcomes at 8- or 16-weeks post-randomization. Most intervention participants did not achieve 50% reduction in vasomotor symptoms despite demonstrated ability to correctly do paced respiration and daily practice. Statistically significant differences in secondary outcomes at 8- and 16-weeks were small, not likely to be clinically relevant, and as likely to favor intervention as breathing control. Conclusions: Paced respiration is unlikely to provide clinical benefit for vasomotor or other menopausal symptoms in breast cancer survivors or menopausal women without cancer.
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    Research in Palliative and End-of-Life Communication and Training (RESPECT) Center: Year 3 2012-2013
    (Office of the Vice Chancellor for Research, 2013-04-05) Hickman, Susan E.; Haase, Joan E.; Sachs, Greg
    The mission of the Research in Palliative and End-of-Life Communication and Training (RESPECT) Center is to build a collaborative, interdisciplinary scientific community of researchers and clinicians to work together to advance the science of communication in palliative and end-of-life care across the lifespan. Center Goals: • Accelerate the development of innovative descriptive and intervention research trials relevant to communication and decision-making in children, adolescents, adults, and elders with serious and/or life-threatening illness • Develop new community partnerships for translational science to enhance palliative and end-of-life care research and practice • Create mentorship opportunities for developing scholars who will become the next generation of productive, passionate palliative and end-of-life care researchers The RESPECT Center is comprised of 19 faculty, 3 post-doctoral trainees and 3 staff members. Faculty meet twice a month to review and provide feedback to support the development of ideas and submission of research grants. In the 2011-2012 funding year, RESPECT Center faculty submitted 11 grants and received over $7.9 million dollars in funding, representing an increase of 21 % from the previous year. Additionally, faculty collaborated on the dissemination of findings and published XX articles on palliative and end-of-life care. The Center’s Visiting Scholar Series has hosted visits by 7 nationally recognized experts to consult with faculty and share their expertise with the community. On March 1, 2013, the RESPECT Center hosted a one-day statewide conference to bring together researchers and clinicians in Carmel, Indiana. The conference entitled, Translating Research into Best Practice: Improving Palliative and End-of-life Care, was attended by approximately 150 participants from 45 organizations. Finally, the RESPECT Center awarded 5 pilot study grants to help researchers develop critically important pilot data and continues to mentor developing scholars interested in the science of communication in palliative and end-of-life care.
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    Surgical Model of Menopause Symptoms: GABA’S Role in Anxiety and Hot Flashes
    (Office of the Vice Chancellor for Research, 2013-04-05) Frink, Anna
    Menopause is the permanent cessation of the primary functions of the human ovaries: the ripening and release of the ova, and the release of hormones that create the uterine lining. The transition from a reproductive to non-reproductive state is a result of a reduction in sex hormone production by the ovarian follicular cells due to their degeneration. For some women, the accompanying signs of and effects that can occur during the menopause transition years can significantly disrupt their daily activities and sense of well-being; symptoms include vasomotor instability (hot flashes and night sweats), anxiety, and sleep disruption. Unfortunately, animal modeling to understand these symptoms, particularly “hot flashes” has been limited and lacks predictive and construct validity. We have developed a novel model of “hot flashes” by injecting a 3 mg/kg (intraperitoneal administration) dose of the anxiogenic drug FG-7142 (a partial inverse agonist at the benzodiazepine site on the GABAA receptor) following bilateral ovariectomy. Previous work in our lab has determined that this injection elicits a rapid, 9° Celsius increase in tail skin temperature (the indicator of the “hot flash” response in a rat) in ovariectomized rats but not in sham-operated control rats. However, the neural sites that mediate this response are unknown. We hypothesized that there are significant differences in either the anatomical sites involved in the “hot flash” response in ovariectomized rats or the extent of activation of the same neural sites. To test this hypothesis, female rats were either bilaterally ovariectomized or sham-ovariectomized; following recovery, rats were given a 3 mg/kg dose of FG-7142 or vehicle and perfused 90 min later. Tissue was processed and stained for the immediate early gene product c-fos. It was determined that the ovariectomized rats had a hyperactive response in the hypothalamic brain region associated with anxiety and thermoregulation (i.e., dorsal medial hypothalamus).
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    Wnt Signaling in Zebrafish Fin Regeneration: Chemical Biology Using GSK3b Inhibitors
    (Office of the Vice Chancellor for Research, 2013-04-05) Curtis, Courtney; Sarmah, Swapnalee; Collins, Kayla; Chu, Shaoyou; Sato, Mas; Sanchez-Felix, Manuel; Marrs, James A.
    Bone growth can be impaired due to disease, such as osteoporosis, and Wnt signaling pathways regulate bone growth. The parathyroid hormone (PTH) is therapeutic for anabolic bone growth (bone building), which activates Wnt signaling, leading to bone growth. GSK3b (glycogen synthetase kinase 3 beta) protein inhibitors activate Wnt signaling, including in bone growth models. Our study utilized a zebrafish model system to study Wnt activated fin regeneration and bone growth. Wnt signaling is the first genetically identified step in fin regeneration, and bony rays are the main differentiated cell type in fins. Thus, zebrafish fin regeneration may be a useful model to study Wnt signaling mediated bone growth. Fin regeneration experiments were conducted using various concentrations of GSK3b inhibitor compound for different treatment periods and regenerative outgrowth was measured at 4 and 7 days post amputation. Experiments revealed continuous low concentration (5-6 nM) treatment to be most effective at increasing regeneration. Higher concentrations inhibited fin growth, perhaps by excessive stimulation of differentiation programs. In situ hybridization experiments were performed to examine effects of Gsk3b inhibitor on Wnt responsive gene expression. Initial experiments show temporal and spatial changes on individual gene markers following GSK3b inhibitor treatment. Additionally, confocal microscopy and immunofluorescence labeling data indicated that the Wnt signaling intracellular signal transducer, betacatenin, accumulates throughout Gsk3b inhibitor treated tissues. Finally, experiments are underway to quantify phosphohistone-3 staining in regenerating tissue to measure effects of Gsk3b inhibitor on cell proliferation. Together, these data indicate that bone growth in zebrafish fin regeneration is improved by activating Wnt signaling. Zebrafish Wnt signaling experiments provide good model to study bone growth and bone repair mechanisms, and may provide an efficient drug discovery platform.
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    Indiana Center for Intercultural Communication: Translating Health Discourse Research into Action
    (Office of the Vice Chancellor for Research, 2013-04-05) Connor, Ulla
    The Indiana Center for Intercultural Communication (ICIC) is a university-based research and service organization created to enhance links between the city of Indianapolis, the state of Indiana, and cultures/nations throughout the world. ICIC conducts internationally recognized research on language and intercultural communication and applies its expertise to benefit the wider community. The Center also offers group training programs and individualized tutoring in language for specific purposes and intercultural communication to students, faculty, medical residents, postdoctoral researchers, and business professionals in the community as well as international language educators. ICIC’s research focuses on health discourse from the perspective of intercultural rhetoric. The Center’s strong linguistic background provides a unique multimodal approach to the study of factors and forms of interaction and communication that impact medication adherence, risk comprehension, and patient disease management and decision-making. In keeping with the Signature Center Initiative mandate to conduct research that translates into practice, the results of ICIC’s research translate into action in the form of training to healthcare providers and guidelines for patient-tailored language and communication strategies. This poster features results from recent ICIC research projects, among them a study of linguistic indicators related to diabetes patient self-management and an intercultural analysis of sources of medical information in Spanish-speaking diabetes patients. Also featured are ongoing and future projects: a psychosociolinguistic study of patient voices to be applied to the development of patient-tailored messaging and the health-literacy oriented redesign of the Walther Cancer Center information portal for patients.
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    Carbon Dioxide Challenge and Hot Flashes
    (Office of the Vice Chancellor for Research, 2013-04-05) Dorsey, Sarah E.; Carpenter, Janet S.
    Little is known about the pathophysiology of menopausal hot flashes, although there appear to be many similarities between hot flashes and panic attacks. While hot flashes occur at random and are difficult to study, there is a method of testing panic attacks. A Carbon Dioxide (CO2) Challenge is a validated method that has been used to induce panic attacks in a laboratory setting. The aim of this study is to test whether a CO2 Challenge using inhalations of 20% and 35% CO2 can provoke a hot flash in menopausal women. We hypothesize that women who have many hot flashes each day (4+) will have a hot flash when exposed to the increased concentration of CO2 using this challenge. Six healthy women attended a study session lasting ninety minutes. In this placebo controlled, cross-over study, women inhale room air, 20% CO2 for 40 seconds, rest for 15 minutes, and 35% CO2 using a double-breath vital capacity inhalation. Anxiety was measured on a numeric rating scale (NRS) and a State Trait Anxiety Inventory (STAI). Most participants have reported a hot flash within minutes of the CO2Challenge. There have been no significant changes in anxiety during the study. Findings provide evidence of the proposed link between hot flashes and panic.
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    Pancreatic Cancer Center: Providing the Research Tools Necessary to Advance Pancreatic Cancer Patient Care
    (Office of the Vice Chancellor for Research, 2013-04-05) Korc, Murray; Kelley, Mark R.
    There were approximately 43,000 new cases of pancreatic ductal adenocarcinoma (PDAC) in the U.S. in 2010, and approximately 37,000 deaths. PDAC thus constitutes the fourth leading cause of cancer deaths, and PDAC patients have a dismal 5-year survival rate of 6%; approximately 75% of patients die within the first year after diagnosis. PDAC is notoriously resistant to chemotherapy and radiation and even with our best treatment options, a complete margin-negative surgical resection, few patients achieve long-term survival. Despite these statistics, surprisingly only a small number of NCI-designated cancer centers have a specialized pancreatic cancer program. The creation of the IUPUI Signature Center for Pancreatic Cancer Research has been the foundation for putting IUPUI, the IU School of Medicine, Purdue University and the IU Simon Cancer Center at the forefront of pancreatic cancer treatment and research across the nation. The Signature Center, comprised of basic, translational and clinical researchers, represents the continuum of the disease from biological / molecular investigation to clinical trials. Funding from the Signature Center Initiative is being utilized to develop genetically engineered mouse models, generate orthotopic pancreatic cancer mouse models as well as provide funding for peer reviewed pilot projects. Establishment and characterization of these in vivo models provides the groundwork to be used by all members in their translational research projects; support of pilot projects provides preliminary data and identification of projects to be used in a SPORE application. Additionally, work has begun on a web portal to promote and educate both patients and clinicians about the IUSCC Pancreas Cancer Clinic which became operational in 2010. Taken together these activities provide the infrastructure to support pancreas cancer research at IU across the continuum of bench to bedside to practice. The availability of these resources to all members promotes inter-disciplinary collaborations aimed at increasing our understanding of pancreatic cancer so that advancements can be made in diagnosis, prevention and treatment of this malignancy.
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    Increased Ischemic Cardiac Deaths in Central Indiana in Summer Months Compared to Winter Months
    (Office of the Vice Chancellor for Research, 2013-04-05) Cook, Shannon; Lloyd, Frank, Jr.; Ballew, Alfie; Sandusky, George E.
    Cardiovascular diseases have been the leading cause of death in the United States for several decades. Despite sustained declines in the mortality rates from these diseases, the magnitude of the disease is still staggering. One large recent study, using data on hundreds of heart attacks documented in the National Registry of Myocardial Infarction, found that 53 percent more cases in winter than in summer. The primary culprit, many believe, is temperature. Cold weather narrows coronary arteries and raises blood pressure, stressing the heart. Physical strain and ruptured plaques caused by shoveling snow are also commonly cited. But in a recent study, two researchers, found that the risk increases even in warm climates. Analyzing death certificates in seven regions with different climates, Los Angeles, Texas, Arizona, Pennsylvania, Massachusetts and others found that cardiovascular deaths rose up to 36 percent between summer and winter, regardless of climate and temperatures In this study we evaluated the incidence of ischemic cardiomyopathy in the Central Indiana area in the winter months compared to the summer months for the years 1998 to 2002. Approximately 5325 deaths were seen in the Marion County Morgue in central Indiana in this time period. There were 609 ischemic cardiac deaths seen in the summer (March 15th through October 15th) compared to 434 ischemic cardiac deaths seen in the winter (October 15th through March 15th). The deaths by years in the summer were 129, 131, 92, 127, and 130 and in the winter were 95, 96, 90, 96, and 57 respectively. In conclusion, this study was consistent with the outcome as the previous study done in multiple northern and southern cities in the country.
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    Facilitators and Barriers to Illness Management and Recovery Implementation
    (Office of the Vice Chancellor for Research, 2013-04-05) White, Dominique A.; McGuire, Alan B.; Salyers, Michelle P.
    Illness Management and Recovery (IMR) is an evidence-based program designed to help people with severe mental illness better manage their illness and achieve personally meaningful goals. IMR has shown improved outcomes including better coping and reduced psychiatric symptoms. There have been some difficulties implementing IMR, even within programs that have received IMR training. The purpose of the current study was to examine the differences between facilitators and barriers for implementing IMR as perceived by providers of IMR and non-providers of IMR in order to identify potential targets for implementation strategies. A national online survey was conducted with VA Medical Centers (VAMCs), resulting in 151 responses representing 107 VAMCs nationwide. Survey respondents included local recovery coordinators (LRCs) and staff referred by the LRC for being knowledgeable regarding IMR. The current analyses focused on two open-ended questions pertaining to facilitators and barriers to implementation. The authors independently developed codes through an iterative process to categorize responses. We then established overall consensus on codes and applied those codes to each open-ended response. Chi-square tests were performed on each category to determine differences between provider and non-provider perceived facilitators and barriers. Differences in identified facilitators and barriers were discovered between the providers and non-providers respondents. Overall barriers and facilitators to implementation are described. Identifying facilitators and barriers that differ between providers and non-providers can provide insight into areas that may impact implementation. By understanding these differences we can provide carefully targeted interventions to increase implementation, for example, gaining support from individuals who do not directly provide IMR, could reinforce the experiences of direct service providers.
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    THE INDIANA CENTER FOR BREAST CANCER RESEARCH: PROGRESS REPORT
    (Office of the Vice Chancellor for Research, 2013-04-05) Nakshatri, Harikrishna; Sledge, George W., Jr.; Badve, Sunil; Bales, Casey; Gilley, David P.; Goswami, Chirayu; Wells, Clark D.; Guise, Theresa; Ziner, Kim W.
    The mission of IUPUI breast cancer center is to address prevention, early detection, and treatment of breast cancer through translational projects, supportive cores, and synergistic programs. This poster details our efforts improve resources for breast cancer research and efforts to develop multi-PI investigator proposals. The Signature Center Initiative has developed two web resources: the Breast Cancer Prognostics Database (BCDB) to study prognostic implications of genes of interest in publically available breast cancer databases and PROGmiR, a microRNA database. The BCDB can be used to study overall, recurrence free and metastasis free survival in large patient series. PROGmiR allows investigators to study the prognostic importance of microRNAs. PROGmiR has recently been published and has been accessed by investigators from several countries. The signature center has also devoted considerable efforts in developing tumor tissue resource. Tissue Bank includes a total sample of N = 500 cases with 30% non-Caucasian cases from Wishard Memorial Hospital. Currently 237 cases have been assembled into a Tissue Microarray with clinical and follow up data. The breast cancer center has funded three pilot projects. Drs. Clark Wells, S. Badve, and G. Sandusky are collaborating on the project: “Histologic Analysis of the Protein Levels of Amot130, AmotL1 and YAP in Normal, Hyperplastic and Invasive Breast Cancer Tissues”. This project is investigating localized protein expression in paraffin-embedded tissues to associate expression levels with disease subtype and patient outcome. Dr. David Gilley and his group are collaborating on the project: “Luminal mammary progenitors are a unique site of telomere dysfunction”. This project is investigating the relationship between telomere dysfunction and breast cancer tumorigenesis. In the third project, Dr. Theresa Guise will be investigating the mechanisms of cancer-associated cachexia. Several multi-PI proposals are under preparation and one proposal with Drs. Nakshatri and Kathy Miller as PIs is currently under review.