http://journals.iupui.edu/index.php/IMPRS/issue/feed Proceedings of IMPRS 2019-01-08T13:23:32-05:00 Anne Nguyen imprs@iupui.edu Open Journal Systems <p>The&nbsp;Indiana Medical Student Program for Research and Scholarship (IMPRS) facilitates IU School of Medicine medical student participation in various medical research and experiential opportunities including laboratory, clinical, and health research outcomes and community health education. The program strives to make a wide variety of research and clinical opportunities accessible to all students, enhance intellectual inquisitiveness, and support excellence in the development of physicians, physician-scientists, and educators.</p> http://journals.iupui.edu/index.php/IMPRS/article/view/22648 A TREM2 dependent control of Microglial and Astrocytic responses in a mouse model of Alzheimer's Disease 2019-01-08T13:23:32-05:00 Nnamdi Achebe imprs@iupui.edu Shweta S. Puntambekar, Ph.D imprs@iupui.edu Bruce T. Lamb imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Alzheimer’s Disease (AD) is characterized by deposition of&nbsp;extracellular&nbsp;amyloid beta plaques resulting in activation of plaque associated CNS glial cells, namely microglia and astrocytes. While extensive research has been directed to understand the role of microglia in neurodegenerative changes in AD, relatively little is known of astrocytic contributions to the disease. Studies using nerve injury models have shown that pro-inflammatory microglia can induce neurotoxic astrocytic phenotypes. In AD, the microglial gene TREM2 has been implicated in mediating neuroprotective immune functions. Research suggests that microglia go through TREM2-independent, followed by TREM2-dependent activation to mediate neuroprotection in diseases like AD, ALS and PD. The central objective of this project is to evaluate whether TREM2 dependent skewing of microglial activation generates neuro-protective/toxic&nbsp;astroglial&nbsp;populations.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>We will use&nbsp;the&nbsp;5XFAD&nbsp;mouse model of AD in this project. Changes in microglial and&nbsp;astroglial&nbsp;activation will be evaluated in&nbsp;4-month-old&nbsp;5xFAD;&nbsp;TREM2<span data-fontsize="11">+/-</span>mice using immunofluorescence and confocal&nbsp;microscopy<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Our results show an increase in&nbsp;proinflammatory, plaque associated microglia expressing MHCII and C1qA in 5XFAD;TREM2+/- mice relative to 5XFAD;TREM2+/+ mice. This is accompanied by an increase in GFAP+S100B- reactive astrocytes in the hippocampus and subiculum.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p>TREM2 deficiency in a mouse model of AD skews the microglia to a proinflammatory phenotype, which may correlate with heightened astroglial reactivity and neurotoxicity. As loss of function mutations in TREM2 have been associated with an increased risk of neurodegenerative changes, these data shed light on how TREM2-mediated microglial-astrocytic crosstalk may influence disease progression.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> 2018-12-06T16:03:42-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22654 Efficacy and Safety of Fecal Microbiota Transplantation for the treatment of Clostridium difficile Infection in Patients with Liver Cirrhosis: a single center experience 2019-01-08T13:23:32-05:00 Dana Alhaffar, BS imprs@iupui.edu Emmalee Phelps, BS imprs@iupui.edu Monika Fischer, MD imprs@iupui.edu <p><strong>Background</strong><strong>&nbsp;and Hypothesis</strong><strong>:</strong>&nbsp;Fecal microbiota transplant (FMT) is an effective therapy&nbsp;approaching a 90% success rate for recurrent and severe CDI. However,&nbsp;patients with liver cirrhosis are generally excluded from FMT trials due to concerns of infectious complications. We aimed&nbsp;to investigate the efficacy and safety of&nbsp;FMT&nbsp;in these patients.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Project Methods</strong><strong>:&nbsp;</strong>Electronic medical records (Cerner) and an institutional FMT database (REDCap) were utilized to gather data on patient demographics, medical history, and follow-up.&nbsp;Inclusion&nbsp;criteria were&nbsp;the diagnosis of liver cirrhosis and&nbsp;FMT to treat CDI. The primary outcomes were FMT success&nbsp;at 8 weeks&nbsp;and adverse events within 12 weeks post-FMT.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Results:</strong>&nbsp;Among the 267&nbsp;patients in the database, 15&nbsp;had&nbsp;liver cirrhosis. Among these, 47% (N=7) were female. The average age was 61 years&nbsp;(range&nbsp;28-83) and&nbsp;they&nbsp;received FMT between 2014 and 2017.&nbsp;There were 12 (80%)&nbsp;patients with&nbsp;recurrent CDI and 3 (20%)&nbsp;with&nbsp;severe CDI.&nbsp;Eleven patients had decompensated cirrhosis;&nbsp;Child-Pough&nbsp;scores were A:&nbsp;N=4,&nbsp;B: N=8, and C: N=3.&nbsp;Five&nbsp;(33%)&nbsp;failed before 8 weeks&nbsp;and needed 1-3 additional FMTs for cure. Fourteen&nbsp;(93.3%)&nbsp;patients experienced adverse events.&nbsp;Five patients experienced unrelated SAEs (Table).&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Conclusion:</strong>&nbsp;Patients with liver cirrhosis failed FMT more often than non-cirrhotic historical controls.&nbsp;While numerous AEs and SAEs were reported, few of the AEs were possibly related to the FMT and none of the SAEs were FMT-related.&nbsp;Importantly, no infectious complications were observed. Larger, multicenter studies are needed to establish efficacy and safety of FMT in&nbsp;cirrhotics&nbsp;before it can&nbsp;be&nbsp;recommended for widespread use.</p> 2018-12-06T16:04:50-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22655 Inhibition of IRS-1 Alters Retinal Circadian Clock 2019-01-08T13:23:31-05:00 Maaz Arif imprs@iupui.edu Deepa Mathew imprs@iupui.edu Ashay Bhatwadekar imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><strong>&nbsp;</strong>&nbsp;<br>Life on Earth has adapted to a 24-hour cycle of light and darkness.&nbsp; Circadian physiology coordinates&nbsp;temporal metabolism, hormone cycling, and sleep using clock genes. It is documented that dysregulation of clock gene expression is a key factor in&nbsp;the&nbsp;pathogenesis of diabetic retinopathy. Our goal was to explore the relationship between clock genes and&nbsp;the retina in diabetic milieu, and we hypothesized that disrupting downstream insulin signaling&nbsp;in a manner&nbsp;similar&nbsp;to&nbsp;diabetes&nbsp;in the retina would also affect the circadian clock.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods:</strong>&nbsp;<br>In this mouse study, we used a Per2::Luc fusion protein to perform&nbsp; real-time bioluminescent recording of circadian rhythms. We used SecinH3 to inhibit&nbsp;Insulin Receptor Signaling&nbsp;(IRS-1). In isolated retinas, we modulated IRS-1 to mimic the diabetic condition of impaired insulin signaling;&nbsp;this allowed us to directly quantify circadian&nbsp;rhythms in the retina.&nbsp;<br><strong>Results:</strong>&nbsp;<br>Our results show that IRS-1 inhibition by SecinH3 altered the gene expression of Per2, a clock regulatory gene, over the controls. There was an increase in the period and an apparent phase shift in the presence of 100uM SecinH3.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong>&nbsp;<br>Our findings can help us understand the role of insulin signaling on circadian rhythms of the retina and provide another temporal dimension to view diabetic retinopathy disease progression. Ultimately, further studies and a closer understanding of the roles of molecular clocks and insulin signaling may help to develop novel therapeutics for treating some of the harmful effects of diabetes.</p> 2018-12-06T16:06:46-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22656 Assessment of nutrition status in transplant patients using imaging, serologic markers and functional testing: Which best predicts early reversal of malnutrition? 2019-01-08T13:23:31-05:00 Sam Atoa imprs@iupui.edu Richard S. Mangus imprs@iupui.edu <p><strong></strong><strong>Background and Hypothesis:</strong><strong>&nbsp;</strong>Previous studies have shown that patients with malnutrition have worse clinical outcomes which lead to longer hospital stays and increased costs. Little has been studied in regards forms of testing such as functional 5M walk tests and serologic testing in predicting nutritional status.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods:</strong><strong>&nbsp;</strong>Adults with end-stage liver, kidney, or pancreatic failure and with pre-transplant computed tomography (CT) imaging were selected from the transplant database. Each group was separated by organ and compared to each other by each nutritional measurement. Measures of nutrition status included a scaled scoring of core muscle mass, and visceral and subcutaneous fat stores, protein and albumin serum levels, BMI and sarcopenic index.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong>&nbsp;It is clear that&nbsp;Liver patients started off much more malnourished than other organ&nbsp;groups as indicated by&nbsp;the low protein and albumin levels at day 0.&nbsp;Liver patients with severe&nbsp;sarcopenia&nbsp;continued to lose weight after 90 days despite increased albumin levels&nbsp;which&nbsp;suggests there is a rapid and significant loss of weight post-transplant due to diuresis&nbsp;which doesn’t reverse until around day 60.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong>&nbsp;Serologic testing and imaging seemed to be good indicators of early reversal of malnutrition while functional testing did not. These finding will be&nbsp;analyzed&nbsp;against a control group&nbsp;to see which best predicts&nbsp;clinical outcomes such as length of post-operative hospital stays and fall risks. Being able to predict outcomes through nutritional status will help us to better prescreen high risk transplant candidates.</p> 2018-12-07T09:11:47-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22657 Defining the function of a novel TNF receptor superfamily member 2019-01-08T13:23:31-05:00 Joseph Atumonye imprs@iupui.edu Matthew J. Turner imprs@iupui.edu Hongming Zhou imprs@iupui.edu Radomir Slominski imprs@iupui.edu Avery Dawes imprs@iupui.edu <p><strong>Background:</strong><span data-ccp-props="{}">&nbsp;</span></p> <p>Insulin Growth Factor Like 1 Receptor (IGFLR1) is a putative TNF receptor superfamily member of unknown function. Transcripts for&nbsp;IGFLR1 are most abundant in T cells in mice and several leukocyte subsets in humans.&nbsp;A major limitation to understanding IGFLR1 function is the lack of biochemical data regarding IGFLR1 expression and processing&nbsp;in leukocytes.<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Experimental Design:</strong><span data-ccp-props="{}">&nbsp;</span></p> <p>A&nbsp;panel of human leukocyte and keratinocyte cell lines was screened for&nbsp;<em>IGFLR1</em>&nbsp;transcript expression by quantitative PCR. Immunoblotting was then&nbsp;used&nbsp;to detect IGFLR1 protein and characterize which isoform(s) were expressed.&nbsp;Chimeric IGFLR1 construct that could be used to mimic IGFLR1 activation was&nbsp;also&nbsp;generated. This chimeric protein, hNGFR-DmrB2-&nbsp;hIGFLR,&nbsp;contains two&nbsp;DmrB&nbsp;domains that allow for&nbsp;multimerization&nbsp;in the presence of AP20187.&nbsp;<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Results:&nbsp;</strong>&nbsp;&nbsp;<span data-ccp-props="{}">&nbsp;</span></p> <p><em>IGFLR1</em>&nbsp;transcript&nbsp;expression varied between&nbsp;hematopoietic cell lines with relatively low expression in MOLT4 cells (T cell line), intermediate expression in IM9 and ARH77 cells (B cell lines) and high expression in MKB cells (T cell line). Immunoblotting in these cell lines revealed a similar&nbsp;protein signal expression&nbsp;pattern. Immunoblotting also suggested that the most abundant isoform of IGFLR1 was likely isoform c, which lacks ligand-binding and transmembrane domains.&nbsp;With respect to the hNGFR-DmrB2-hIGFLR1 construct, the chimeric protein was detected in CHO cells by immunoblotting and biochemical analyses confirmed that addition of AP20187 induced&nbsp;multimerization&nbsp;of this protein. These findings confirm the functionality of hNGFR-DmrB2-hIGFLR1.&nbsp;<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Potential Impact</strong>:<span data-ccp-props="{}">&nbsp;</span></p> <p>Biochemical studies of endogenously expressed IGFLR1 in these cell lines suggest differential mRNA splicing may play an important role in the production and function of IGFLR1 isoforms. Future studies using the hNGFR-DmrB2-hIGFLR1 construct in the aforementioned human cell lines can be performed to study IGFLR1 signaling.&nbsp;<span data-ccp-props="{}">&nbsp;</span></p> 2018-12-07T09:14:33-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22658 Impact of excess TGFβ on bone and muscle in condition of diet-induced obesity in mice with Camurati-Engelmann Disease 2019-01-08T13:23:30-05:00 Asma S. Bahrami imprs@iupui.edu Trupti Trivedi imprs@iupui.edu Gabriel M. Pagnotti imprs@iupui.edu Khalid M. Mohammad imprs@iupui.edu Theresa A. Guise imprs@iupui.edu <p><strong>Background</strong><strong>&nbsp;</strong><strong>and</strong><strong>&nbsp;</strong><strong>Hypothesis</strong><strong>:</strong><strong>&nbsp;</strong>Camurati-Engelmann&nbsp;Disease&nbsp;(CED) is&nbsp;characterized by&nbsp;extreme bone&nbsp;turnover and excess TGF-β release.&nbsp;We previously&nbsp;showed&nbsp;that bone-derived TGF-β&nbsp;causes glucose intolerance, increases skeletal muscle weakness,&nbsp;and exacerbates diet-induced&nbsp;obesity in CED&nbsp;mice.&nbsp;However, it&nbsp;is&nbsp;unknown&nbsp;whether glucose intolerance and obesity&nbsp;alter&nbsp;bone and muscle phenotypes.&nbsp;Thus,&nbsp;we hypothesized&nbsp;that&nbsp;impaired&nbsp;glucose&nbsp;metabolism&nbsp;and&nbsp;diet-induced&nbsp;obesity&nbsp;exacerbate&nbsp;bone and muscle loss&nbsp;in&nbsp;a&nbsp;mouse&nbsp;model&nbsp;of&nbsp;CED.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental</strong><strong>&nbsp;</strong><strong>Design</strong><strong>:</strong><strong>&nbsp;</strong>45-week&nbsp;WT&nbsp;and CED&nbsp;mice were fed&nbsp;either high-fat&nbsp;diet&nbsp;(HFD)&nbsp;or low-fat&nbsp;diet (LFD) for&nbsp;15&nbsp;weeks.&nbsp;<em>Ex</em><em>&nbsp;</em><em>vivo</em>&nbsp;bone&nbsp;micro-CT&nbsp;and histomorphometry&nbsp;were&nbsp;used&nbsp;to&nbsp;evaluate&nbsp;bone and muscle.&nbsp;Statistical analysis was performed using&nbsp;GraphPad&nbsp;Prism with p&lt;0.05 considered significant.&nbsp;&nbsp;&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results</strong>:&nbsp;CED mice showed&nbsp;severe&nbsp;cortical and trabecular bone loss in response to diet-induced obesity.&nbsp;Trabecular bone volume&nbsp;was&nbsp;reduced&nbsp;by 37%&nbsp;in L5 vertebrae&nbsp;(p&lt;0.001),&nbsp;16% in&nbsp;tibiae&nbsp;(p&lt;0.05), and&nbsp;7% in&nbsp;femora&nbsp;in CED-HFD&nbsp;compared to&nbsp;WT-HFD.&nbsp;Bone&nbsp;mineral density was&nbsp;reduced&nbsp;(p&lt;0.0001)&nbsp;and&nbsp;cortical porosity was&nbsp;increased&nbsp;(p&lt;0.0001)&nbsp;in CED-HFD&nbsp;vs&nbsp;WT-HFD&nbsp;in femora and tibiae.&nbsp;Bone histomorphometry showed&nbsp;no significant&nbsp;differences in osteoclast&nbsp;number&nbsp;between groups. pSMAD2/3 staining&nbsp;was increased by 25%&nbsp;(p&lt;0.05)&nbsp;and muscle fiber diameter&nbsp;was reduced by 32%&nbsp;(p&lt;0.05)&nbsp;in&nbsp;the&nbsp;tibialis anterior&nbsp;muscle&nbsp;of&nbsp;CED mice&nbsp;compared to WT, with&nbsp;greater&nbsp;changes&nbsp;in&nbsp;HFD-fed mice.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion</strong><strong> </strong><strong>and</strong><strong> </strong><strong>Potential</strong><strong>&nbsp;</strong><strong>Impact</strong><strong>:</strong><strong>&nbsp;</strong>High-fat&nbsp;diet&nbsp;and&nbsp;impaired glucose metabolism&nbsp;exacerbates&nbsp;bone&nbsp;loss&nbsp;and&nbsp;increases&nbsp;TGF-β&nbsp;signaling&nbsp;in&nbsp;CED mice.&nbsp;In future&nbsp;studies, inhibiting&nbsp;TGF-β&nbsp;signaling and&nbsp;reducing adiposity&nbsp;may&nbsp;prevent&nbsp;glucose intolerance and&nbsp;musculoskeletal deterioration&nbsp;in conditions&nbsp;of high bone turnover.<strong>&nbsp;</strong></p> 2018-12-07T09:15:55-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22665 Kidney Donor Contrast Exposure and Recipient Outcomes 2019-01-08T13:23:30-05:00 Shivani Bajpai, MS2 imprs@iupui.edu Richard S. Mangus, MD MS FACS imprs@iupui.edu <p><span class="TextRun SCXW45363565" lang="EN-US" xml:lang="EN-US"><span class="NormalTextRun SCXW45363565">The use of contrast media in hospital procedures has been increasing since its conception in 1923. Despite developments in utility and safety overtime, contrast media has been associated with inducing kidney injury in patients. Several studies have investigated contrast-induced nephropathy (CIN) in hospital patients and kidney recipients post-transplant. However, there are few studies that connect donor contrast exposure to recipient kidney outcomes.&nbsp;</span></span><span class="TextRun SCXW45363565" lang="EN-US" xml:lang="EN-US"><span class="NormalTextRun SCXW45363565">This was a single-center, retrospective study on single-organ&nbsp;</span></span><span class="TextRun SCXW45363565" lang="EN-US" xml:lang="EN-US"><span class="NormalTextRun SCXW45363565">deceased&nbsp;</span></span><span class="TextRun SCXW45363565" lang="EN-US" xml:lang="EN-US"><span class="NormalTextRun SCXW45363565">kidney donors and recipients (n=1585) to explore the impact of pre-transplant contrast procedures on</span></span><span class="TextRun SCXW45363565" lang="EN-US" xml:lang="EN-US"><span class="NormalTextRun SCXW45363565">&nbsp;post-transplant</span></span><span class="TextRun SCXW45363565" lang="EN-US" xml:lang="EN-US"><span class="NormalTextRun SCXW45363565">&nbsp;kidney outcomes.</span></span><span class="TextRun SCXW45363565" lang="EN-US" xml:lang="EN-US"><span class="NormalTextRun SCXW45363565">&nbsp;The results indicated that the first, peak, and last serum creatinine values were not useful markers of CIN in kidney donors. An analysis of those donors who had contrast exposure and those who did not, as well as the amount of contrast exposure in the donor prior to transplant did not conclude significant impact on the recipient kidney outcomes at time points ranging from 7 days to 1-year post transplant. This data provides the largest statistical evidence currently available on this topic; it establishes the foundation for various research developments moving forward.</span></span><span class="EOP SCXW45363565" data-ccp-props="{}">&nbsp;</span></p> 2018-12-07T09:17:52-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22659 The Examination of non-pharmacologic treatment of pain after spinal cord injury 2019-01-08T13:23:30-05:00 J. A. Piatt imprs@iupui.edu L. Eldridge imprs@iupui.edu J. M. Baker imprs@iupui.edu <p><strong>Background</strong>: One of the primary debilitating secondary health conditions experienced by individuals&nbsp;living&nbsp;with a spinal cord injury (SCI) is chronic pain. Approximately, over 30% of SCI patients endure chronic pain after sustaining the injury, and engage in opioid pharmacotherapy as the first form of treatment. The increase in use and misuse of prescribed opioids for chronic pain can lead to both physical and psychological health risks. This danger is exacerbated by the notion that a large percentage&nbsp;of&nbsp;the SCI population&nbsp;have a pre-existing condition of drug and alcohol abuse and addiction.&nbsp;This study will&nbsp;examine how pain is actually being addressed through non-pharmaceutical methods among the SCI adult population.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design</strong>:&nbsp;Employing a cross-sectional web survey design with a convenience sample of&nbsp;adults&nbsp;with a SCI. A Qualtrics survey is currently being administered to known individuals with SCIs via email. The survey questions will illuminate what pain management strategies are being implemented in the SCI population within the US.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Anticipated Results</strong>:<strong>&nbsp;</strong>The&nbsp;results from the data will provide insight on what non-pharmacological interventions can be employed in place of or in combination with the pharmacological management. This will allow community-based rehabilitation therapies to&nbsp;incorporate&nbsp;appropriate pain management strategies.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Potential Impact</strong>: Non-pharmacological interventions may hold the answer in treating chronic pain in the SCI population by limiting or eliminating the use of opioids. This study will help develop the most appropriate non-pharmacological intervention to test in quasi-experimental clinical trials, and ultimately minimize the use of opioids for chronic pain.</p> 2018-12-07T09:19:00-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22660 A Novel Small Molecule Therapy for Corneal Neovascularization 2019-01-08T13:23:30-05:00 Zachary Barry imprs@iupui.edu Bomina Park imprs@iupui.edu Timothy W. Corson imprs@iupui.edu <p><strong>Background and Hypothesis:&nbsp;</strong>Corneal neovascularization (CNV) is&nbsp;characterized by&nbsp;abnormal blood vessel growth&nbsp;in the&nbsp;avascular cornea. CNV can be&nbsp;caused by multiple insults such as trauma, infection, and immunological diseases. Current treatments&nbsp;have partial efficacy and associated&nbsp;side effects,&nbsp;revealing&nbsp;a need for novel treatments.&nbsp;<span data-ccp-props="{}">&nbsp;</span></p> <p>We&nbsp;identified the enzyme soluble epoxide hydrolase (sEH) as a target of an&nbsp;antiangiogenic small molecule&nbsp;we developed,&nbsp;SH-11037.&nbsp;SH-11037 was&nbsp;antiangiogenic in mouse models for retinal and&nbsp;choroidal&nbsp;neovascularization.&nbsp;However,&nbsp;its effect&nbsp;on CNV has not been explored. We hypothesize that inhibition of&nbsp;sEH with SH-11037&nbsp;will block CNV.<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Experimental Design</strong><strong>&nbsp;or Project Methods:</strong><strong>&nbsp;</strong>To validate&nbsp;sEH’s relevance&nbsp;in&nbsp;CNV, we assessed the effects of&nbsp;inhibition of sEH in an alkali burn CNV mouse model, treating the eyes with either&nbsp;eyedrops&nbsp;of SH-11037 or another&nbsp;known&nbsp;sEH&nbsp;inhibitor, t-AUCB.&nbsp;Neovascularization&nbsp;was determined by&nbsp;clinical assessment&nbsp;and immunohistochemistry. Toxicity in the retina was assessed by optical coherence tomography (OCT).&nbsp;Eyedrops&nbsp;of&nbsp;dexamethasone&nbsp;(0.1% and 0.03%) were&nbsp;positive controls.&nbsp;<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Results:&nbsp;</strong>Clinical&nbsp;assessment&nbsp;indicated&nbsp;that&nbsp;there was a strong trend towards a decrease in CNV in&nbsp;the&nbsp;0.1%&nbsp;dexamethasone&nbsp;control group (p&nbsp;= 0.0509).&nbsp;Further data generation is underway, but we&nbsp;expect&nbsp;to see decreased CNV in the SH-11037 and t-AUCB experimental groups, compared to the vehicle (PBS) control group.&nbsp;<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:&nbsp;</strong>Upon completion of this study there is potential for a new therapeutic target for reducing CNV.&nbsp;This&nbsp;study&nbsp;provides&nbsp;the&nbsp;assessment of&nbsp;sEH’s&nbsp;involvement&nbsp;in&nbsp;CNV, which opens future areas of study.&nbsp;</p> 2018-12-07T09:19:48-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22661 Effects of Propofol on Transcytosis in an IPSC Derived Blood Brain Barrier Model 2019-01-08T13:23:30-05:00 Dylan Bieber imprs@iupui.edu Jason Hughes imprs@iupui.edu Olivia Neese imprs@iupui.edu Scott Canfield G. Canfield imprs@iupui.edu <p><strong>Background:</strong>&nbsp;In 2016, the FDA released a report concerning the use of anesthetics in young children and pregnant women.&nbsp;This report states that prolonged or repeat exposure to anesthetic may lead to neurodevelopmental delay. Previously,&nbsp;Canfield et al., had determined a method for developing a human blood brain barrier model from induced pluripotent stem cells (iPSC). Preliminary data has shown that exposing this&nbsp;model to&nbsp;propofol&nbsp;at&nbsp;relevant concentrations&nbsp;significantly reduces barrier&nbsp;strength and&nbsp;may promote leakiness of the blood brain barrier.<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Design/Methods:&nbsp;</strong>Our efforts during these ten weeks&nbsp;focused&nbsp;on the effects of&nbsp;propofol&nbsp;on transcellular&nbsp;mechanisms in&nbsp;iPSC-derived&nbsp;brain microvasculature endothelial cells (BMEC).&nbsp;After exposing&nbsp;to&nbsp;propofol,&nbsp;fluorescently labeled dextran&nbsp;transcytosis&nbsp;and accumulation&nbsp;was analyzed on&nbsp;a&nbsp;fluorescent plate reader.&nbsp;Specifically, we monitored the transcellular movement of different molecular weighted&nbsp;dextrans.<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Results:</strong>&nbsp;Treatment of BMECs with 50uM&nbsp;propofol&nbsp;increased&nbsp;transcytosis&nbsp;and accumulation of 10kDa dextran as compared to control. Increased transcytosis in the absence of increased accumulation of 3kDa dextran may provide evidence of paracellular transport.&nbsp;Transcytosis and accumulation of 40kDa dextran were unchanged between treatment and control groups. These data&nbsp;may provide evidence that&nbsp;propofol&nbsp;affects&nbsp;transcytosis&nbsp;mechanisms&nbsp;differently.<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Potential Impact:&nbsp;</strong>We hope to more fully understand the mechanism by which anesthetics such as&nbsp;propofol&nbsp;effect the blood brain barrier.&nbsp;Due to the presence of tight junction proteins, transcytosis is an important mechanism for moving materials into the brain parenchyma. Further research&nbsp;will need to be done to determine the mechanism by which&nbsp;propofol&nbsp;affects BMEC&nbsp;transcytosis.&nbsp;&nbsp;</p> 2018-12-07T09:21:29-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22662 Forever-Fit Summer Camp 2019-01-08T13:23:29-05:00 Anthony O. Boateng, BA imprs@iupui.edu Lisa Yazel-Smith, MS, MCHES CCRP imprs@iupui.edu Brett McKinney, BS imprs@iupui.edu Katie Haberlin, MPH, CHES imprs@iupui.edu Tamara Hannon, MD, MS imprs@iupui.edu Patrick Perry, MPH imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><span data-ccp-props="{&quot;134233117&quot;:true,&quot;134233118&quot;:true,&quot;134233279&quot;:true,&quot;201341983&quot;:2,&quot;335559740&quot;:288}">&nbsp;</span></p> <p>The objective of this study was to evaluate anthropometric and physical fitness measures from participants in the Forever-Fit Summer Camp (FFSC) between the years 2013 and 2017, comparing baseline and post-participation values. We hypothesized that participation in the FFSC would decrease the BMI Z-score of the campers during the 6-week program, as well as improve physical fitness measures. Further, we hypothesized that there would be an overall decrease in BMI and weight seen in campers who participated for multiple years.<span data-ccp-props="{&quot;134233117&quot;:true,&quot;134233118&quot;:true,&quot;134233279&quot;:true,&quot;201341983&quot;:2,&quot;335559740&quot;:288}">&nbsp;</span></p> <p><strong>Experimental Design:</strong><span data-ccp-props="{&quot;134233117&quot;:true,&quot;134233118&quot;:true,&quot;134233279&quot;:true,&quot;201341983&quot;:2,&quot;335559740&quot;:288}">&nbsp;</span></p> <p>In this 5-year cross-sectional evaluation, a total of 64&nbsp;participants were included. During FFSC, biometrics, strength, endurance and flexibility were compared at baseline (Week 1) and 6 weeks after. This&nbsp;data from participants was compared using paired T-tests and compared the BMI Z-Score of campers over the years using repeated measures ANOVA.<span data-ccp-props="{&quot;134233117&quot;:true,&quot;134233118&quot;:true,&quot;134233279&quot;:true,&quot;201341983&quot;:2,&quot;335559740&quot;:288}">&nbsp;</span></p> <p><strong>Results:</strong><span data-ccp-props="{&quot;134233117&quot;:true,&quot;134233118&quot;:true,&quot;134233279&quot;:true,&quot;201341983&quot;:2,&quot;335559740&quot;:288}">&nbsp;</span></p> <p>Compared to baseline for each year, there was an overall decrease in BMI Z-Score and weight after the 6-week intervention. We observed an increase in strength and endurance, as seen with the 1-mile run and various strength test. Interestingly, we saw a decrease in flexibility in the campers as they progressed through the camp. Further, we observed an overall decrease in BMI Z-Score from 2013 to 2017.&nbsp;<span data-ccp-props="{&quot;134233117&quot;:true,&quot;134233118&quot;:true,&quot;134233279&quot;:true,&quot;201341983&quot;:2,&quot;335559740&quot;:288}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><span data-ccp-props="{&quot;134233117&quot;:true,&quot;134233118&quot;:true,&quot;134233279&quot;:true,&quot;201341983&quot;:2,&quot;335559739&quot;:160,&quot;335559740&quot;:288}">&nbsp;</span></p> <p>The FFSC 6-week summer program had significantly decreased BMI and improved fitness measures. The activities performed in the FFSC could be implemented in other programs for youth to combat chronic conditions, such as Type 2 Diabetes.</p> 2018-12-07T09:22:28-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22663 Elevated Airway Eosinophils is Associated with Lower Airway Haemophilus 2019-01-08T13:23:29-05:00 Vyvian C. Borse imprs@iupui.edu Sydney E. Ross, MS imprs@iupui.edu Alexis A. McEntire, BS imprs@iupui.edu James Slaven, MS imprs@iupui.edu Kirsten M. Kloepfer, MD MS imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><strong>&nbsp;</strong>Early wheezing and persistent cough in&nbsp;young&nbsp;children can be&nbsp;a&nbsp;first indication of asthma. Studies&nbsp;show that&nbsp;infants later diagnosed with asthma&nbsp;commonly exhibit&nbsp;airway microbiome&nbsp;dysbiosis&nbsp;particularly with pathogenic bacteria. Two&nbsp;such&nbsp;bacteria,&nbsp;<em>Moraxella catarrhalis&nbsp;</em>and&nbsp;<em>Haemophilus</em><em>&nbsp;influenzae</em>,&nbsp;can&nbsp;stimulate&nbsp;pro-inflammatory&nbsp;cytokines&nbsp;such as&nbsp;IL-5. Because IL-5 can&nbsp;signal eosinophil&nbsp;production, we hypothesize children with asthma&nbsp;and positive&nbsp;bronchoalveolar lavage&nbsp;fluid&nbsp;(BALF)&nbsp;culture will have elevated BALF eosinophils.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Project Methods:</strong><strong>&nbsp;</strong>Children undergoing clinically indicated bronchoscopy in the Riley Hospital outpatient center were recruited.&nbsp;Chart review&nbsp;was conducted to examine associations between BALF&nbsp;culture, BALF&nbsp;differential cytology, diagnoses,&nbsp;antibiotic history,&nbsp;and demographic data&nbsp;from&nbsp;biobank participants.&nbsp;Exclusion criteria included: diagnosis of cystic fibrosis or pulmonary ciliary dyskinesia;&nbsp;BALF&nbsp;culture not performed; and/or hypocellular sample.&nbsp;Statistical analyses included&nbsp;Student’s t-test, Wilcoxon rank-sum tests, and Chi-Square tests (verified with Fisher’s Exact tests).<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><strong>&nbsp;</strong>94&nbsp;samples were analyzed&nbsp;(37% female,&nbsp;age:&nbsp;1mos – 17&nbsp;yrs).&nbsp;BALF was positive for the following bacteria:&nbsp;<em>M</em><em>. catarrhalis</em><em>&nbsp;</em>(26%),&nbsp;<em>H</em><em>. influenzae</em><em>&nbsp;</em>(28%),&nbsp;<em>S. pneumoniae</em><em>&nbsp;</em>(27%), and&nbsp;<em>S. aureus</em><em>&nbsp;</em>(17%)<em>.</em>&nbsp;<em>Haemophilus</em><em>&nbsp;</em>in BALF&nbsp;was associated with elevated eosinophils (p = .03) and neutrophils (p = .04) and decreased macrophages (p = .001).&nbsp;Asthma diagnosis and&nbsp;prior&nbsp;antibiotic use were not significantly associated with positive BALF culture<em>.</em><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><strong>&nbsp;</strong><em>Haemophilus</em><em>&nbsp;</em>was associated with elevated eosinophils in the airway. The impact of this observation remains unclear.&nbsp;Further research is necessary to determine pathways that lead to these observed changes within the airway.</p> 2018-12-07T09:24:28-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22664 CD33 and TREM2 peripheral gene expression in relation to cortical thickness 2019-01-08T13:23:29-05:00 Abby L. Braun, BS imprs@iupui.edu Apoorva Bharthur Sanjay, MS imprs@iupui.edu Diana O. Svaldi imprs@iupui.edu Liana G. Apostolova, MD imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><strong>&nbsp;</strong>&nbsp;Genome-wide association&nbsp;and whole genome sequencing&nbsp;studies have&nbsp;uncovered over 20 novel&nbsp;Alzheimer’s&nbsp;Disease (AD)&nbsp;risk genes.&nbsp;Many of these genes are involved with neuroinflammation. Neuroinflammation&nbsp;plays a pivotal role in disease development.&nbsp;<em>CD33</em>&nbsp;and&nbsp;<em>TREM2</em>&nbsp;are&nbsp;two&nbsp;immune pathway&nbsp;genes implicated&nbsp;in&nbsp;AD.&nbsp;&nbsp;We studied the&nbsp;association between peripheral blood&nbsp;expression of&nbsp;<em>CD33</em>&nbsp;and&nbsp;<em>TREM2</em>,&nbsp;with&nbsp;cortical&nbsp;thickness&nbsp;– a marker of neurodegeneration in&nbsp;AD.&nbsp; We&nbsp;hypothesized that expression of&nbsp;some&nbsp;these genes&nbsp;would&nbsp;correlate&nbsp;with&nbsp;cortical atrophy&nbsp;in&nbsp;our pooled sample.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods:</strong><strong>&nbsp;</strong>Data&nbsp;from 155&nbsp;subjects&nbsp;(50 NC and 105&nbsp;MCI)&nbsp;were&nbsp;gathered from the UCLA&nbsp;ImaGene&nbsp;study. The imaging data was&nbsp;processed using the&nbsp;FreeSurfer&nbsp;6.0 longitudinal pipeline&nbsp;and cortical&nbsp;anatomy was&nbsp;standardized for all subjects.&nbsp;&nbsp;A GLM analysis using&nbsp;Surfstat&nbsp;investigated the&nbsp;associstion&nbsp;of&nbsp;gene&nbsp;expression&nbsp;levels in peripheral blood&nbsp;and&nbsp;cortical&nbsp;thickness&nbsp;controlling for age, gender, education, and diagnosis&nbsp;and generated 3D visualization maps of these associations.&nbsp;Statistical significance was determined with p set at 0.05.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><strong>&nbsp;&nbsp;</strong><em>CD33</em><em>&nbsp;</em>expression&nbsp;showed a positive correlation with cortical thickness&nbsp;in the right medial, inferior and lateral temporal, lateral parietal, posterior cingulate and inferior lateral frontal cortices.&nbsp;<em>TREM2</em>&nbsp;did not&nbsp;show statistically&nbsp;significant association with&nbsp;cortical atrophy.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><strong>&nbsp;</strong><strong><em>&nbsp;</em></strong>Peripeheral&nbsp;blood<strong><em>&nbsp;</em></strong><em>CD33</em>&nbsp;expression level seems to be lower in individuals with greater cortical atrophy in AD-relevant areas.&nbsp; This contributes to a growing body of research that indicates a role for&nbsp;the immune system and&nbsp;<em>CD33&nbsp;</em>in&nbsp;particular in&nbsp;the pathology of AD and may contribute to future&nbsp;mechanism and biomarker studies.&nbsp;</p> 2018-12-07T09:27:50-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22666 Wound healing in diabetic Ossabaw pigs 2019-01-08T13:23:29-05:00 Cameron Brown imprs@iupui.edu James Byrd imprs@iupui.edu Caleb Eggenberger imprs@iupui.edu Brian Nguyen imprs@iupui.edu Guillermo Ameer imprs@iupui.edu Michael Sturek imprs@iupui.edu Mouhamad Alloosh imprs@iupui.edu Yunxiao Zhu imprs@iupui.edu Chongwen Duan imprs@iupui.edu <p><strong>Background and Hypothesis:&nbsp;</strong>Wound healing drugs are effective in mouse models of diabetes, but&nbsp;have not been tested in diabetic swine, whose skin more closely mimics that of humans. The primary objective was to test the wound healing efficacy of lipid nanoparticles in diabetic&nbsp;Ossabaw&nbsp;miniature swine.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335551550&quot;:6,&quot;335551620&quot;:6,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design and Project Methods:&nbsp;</strong>Diabetes was induced in four&nbsp;Ossabaw&nbsp;miniature swine by ablation of the insulin-producing pancreatic beta cells and 5 months later the pigs received 8 surgically-induced skin wounds.&nbsp;EXCEDE was given at the time of surgery to prevent systemic infections&nbsp;for the first week of wound healing.&nbsp;Wounds were treated with drug-loaded nanoparticles in a hydrogel, an unmodified hydrogel,&nbsp;Promogran&nbsp;Prisma Matrix, or control phosphate-buffered saline&nbsp;(PBS). Photos were taken weekly to compare wound closure and complete skin thickness biopsies were taken for histological assessment.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335551550&quot;:6,&quot;335551620&quot;:6,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong>&nbsp;Severe&nbsp;diabetes was verified with plasma glucose&nbsp;of&nbsp;357±15 mg/dL&nbsp;(mean±SE; n=3), while 1 pig&nbsp;was mildly&nbsp;diabetic&nbsp;(147±18 mg/dL).&nbsp;All&nbsp;pigs&nbsp;exhibited glucosuria.&nbsp;Normal body weight was maintained to mimic human diabetics with poor glycemic control. Complete blood counts confirmed&nbsp;the absence of systemic infection throughout the study.&nbsp;After two weeks, the percent closure&nbsp;by treatment&nbsp;was&nbsp;53±4% for Prisma, 48±7% for the hydrogel, 47±5% for the lipid nanoparticles, and 59±4% for PBS.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335551550&quot;:6,&quot;335551620&quot;:6,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:&nbsp;</strong>The data currently suggest&nbsp;no differences in&nbsp;medication&nbsp;efficacy, but&nbsp;data collection&nbsp;at longer durations of healing&nbsp;is not finished. Beneficial drug effects&nbsp;also&nbsp;may be&nbsp;seen&nbsp;on the composition (histology) of the healed skin, which has not yet been assessed.</p> 2018-12-07T09:28:50-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22667 CHARACTERIZING THE ROLE OF ORBITOFRONTAL CORTEX IN SOCIAL MEMORY 2019-01-08T13:23:29-05:00 Marissa L Bruce imprs@iupui.edu Katharine D. Andrews imprs@iupui.edu Elizabeth A. Lungwitz imprs@iupui.edu William A. Truitt imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Social-enhanced safety learning is a psychosocial process used to reduce fear or anxiety by learning to discriminate fearful versus safe stimuli&nbsp;via a&nbsp;social safety cue.&nbsp; Learning to associate safety with a social cue requires intact social memory.&nbsp;Preliminary data&nbsp;in rats&nbsp;suggests&nbsp;inhibiting the&nbsp;orbitofrontal cortex (OFC)&nbsp;with pharmacologic&nbsp;agents impairs&nbsp;social memory.&nbsp;However,&nbsp;the specific mechanism by which OFC regulates social memory remains unknown.&nbsp;&nbsp;Because the OFC has broad functional implications including valuation, decision-making, social and emotional behaviors, olfaction, and non-social memory,&nbsp;we&nbsp;hypothesized that&nbsp;OFC inhibition was disrupting one of these specific processes, resulting in social memory impairment.&nbsp;&nbsp;&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559731&quot;:720,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Cannulated&nbsp;adult male Sprague-Dawley rats were&nbsp;injected&nbsp;bilaterally in OFC&nbsp;with&nbsp;either&nbsp;saline&nbsp;vehicle, or&nbsp;0.9&nbsp;mM&nbsp;Muscimol, a GABA<span data-fontsize="11">A</span>&nbsp;agonist that&nbsp;transiently inhibits local&nbsp;neuronal activity.&nbsp; At 10 minutes&nbsp;post-injection, rats&nbsp;underwent behavior testing&nbsp;for&nbsp;either:&nbsp;social recognition,&nbsp;novel object recognition, social preference&nbsp;(innate gregariousness),&nbsp;or&nbsp;olfactory discrimination.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Result</strong><strong>s:&nbsp;</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Rats receiving Muscimol injection,&nbsp;but not&nbsp;rats receiving&nbsp;vehicle injection,&nbsp;demonstrated statistically significant impairment of social recognition, observed as a failure to discriminate between two conspecifics.&nbsp;Alternatively, rats receiving Muscimol injection, but not rats receiving vehicle injection,&nbsp;did&nbsp;<em>not</em>&nbsp;demonstrate&nbsp;statistically significant impairment of&nbsp;novel object (non-social) recognition,&nbsp;innate gregariousness, or olfaction, which were all intact in vehicle injected rats.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p>These data suggest&nbsp;OFC may&nbsp;be part of&nbsp;a&nbsp;unique&nbsp;neural circuit specific to social memory.&nbsp;&nbsp;Delineating the circuitry of social memory from&nbsp;non-social memory&nbsp;offers exciting possibilities in the advancement of precision therapies.&nbsp;&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> 2018-12-07T09:29:57-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22668 The Influence of Aging on the Relationship between Retrobulbar Blood Flow and Retinal Microcirculation in Glaucoma Patients 2019-01-08T13:23:28-05:00 Kendall M. Burgett, BS imprs@iupui.edu Brent Siesky, PhD imprs@iupui.edu Alon Harris, MS, FARVO, PhD imprs@iupui.edu <p><strong>Background and Hypothesis</strong>:&nbsp;Glaucoma is a multifactorial&nbsp;disease;&nbsp;therefore,&nbsp;different&nbsp;patient populations&nbsp;may be more susceptible to developing glaucoma due to&nbsp;distinct&nbsp;factors.&nbsp;The&nbsp;hypothesis&nbsp;of this study&nbsp;was that&nbsp;the relationship between retrobulbar blood flow velocity and the amount of avascular area in the&nbsp;peripapillary&nbsp;retina&nbsp;in glaucoma patients&nbsp;differs based on patient age.&nbsp;<span data-ccp-props="{&quot;335551550&quot;:6,&quot;335551620&quot;:6}">&nbsp;</span></p> <p><strong>Project&nbsp;</strong><strong>Methods</strong>: Data&nbsp;from 18&nbsp;glaucoma&nbsp;patients aged&nbsp;≥70 years old&nbsp;(75.9±5.4) and 24 glaucoma patients&nbsp;aged &lt;70&nbsp;(60.5±8.6)&nbsp;were&nbsp;used in this analysis.&nbsp;Peak systolic&nbsp;and end diastolic velocities&nbsp;(PSV/EDV) of nasal and temporal posterior ciliary arteries (N/TPCA)&nbsp;were measured using color Doppler imaging (CDI) in order to assess&nbsp;retrobulbar blood flow velocities.&nbsp;Heidelberg Retinal&nbsp;Flowmetry&nbsp;(HRF) was used&nbsp;to quantify the amount of superior avascular area (SAA) and inferior avascular area (IAA) of the&nbsp;peripapillary&nbsp;retina.<span data-ccp-props="{&quot;335551550&quot;:6,&quot;335551620&quot;:6}">&nbsp;</span></p> <p><strong>Results</strong>: In patients&nbsp;≥70 years of age, a&nbsp;negative&nbsp;correlation was detected&nbsp;between retrobulbar blood flow velocity and IAA&nbsp;(r=−0.45&nbsp;for NPCA-PSV,&nbsp;r=−0.36&nbsp;for NPCA-EDV, r=−0.35 for TPCA-PSV, r=−0.45&nbsp;for TPCA-EDV).&nbsp;This is in contrast to the&nbsp;positive correlation seen in&nbsp;patients &lt;70 years of age&nbsp;(r=0.45&nbsp;for NPCA-PSV, r=0.39&nbsp;for NPCA-EDV, r=0.55&nbsp;for TPCA-PSV, r=0.69&nbsp;for TPCA-EDV).&nbsp;Correlation coefficients between the two age groups were significantly different&nbsp;(p&lt;0.01, p&lt;0.05, p&lt;0.01, and p&lt;0.0001 respectively).<span data-ccp-props="{&quot;335551550&quot;:6,&quot;335551620&quot;:6}">&nbsp;</span></p> <p><strong>Conclusion</strong><strong>&nbsp;and Potential Impact</strong>:&nbsp;The relationship between&nbsp;blood vessels&nbsp;supplying the eye&nbsp;and retinal&nbsp;microcirculation is significantly different based on patient age.&nbsp;This&nbsp;suggests&nbsp;that different age populations may have&nbsp;distinct&nbsp;risk profiles&nbsp;for glaucoma. A more complete understanding of&nbsp;population dependent&nbsp;risk factor profiles may&nbsp;assist&nbsp;glaucoma screening and early detection.&nbsp;<span data-ccp-props="{&quot;335551550&quot;:6,&quot;335551620&quot;:6}">&nbsp;</span></p> <p><span data-ccp-props="{&quot;335551550&quot;:6,&quot;335551620&quot;:6}">&nbsp;</span></p> 2018-12-07T09:30:38-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22669 Quantifying Cigarette Smoke Induced Oxidative DNA Damage of Wild Type & XPC Knockdown Human Bronchial Cells Using Human 8-oxoguanine DNA Glycosylase 1 2019-01-08T13:22:10-05:00 Jarrett Campbell imprs@iupui.edu Huaxin Zhou imprs@iupui.edu Catherine Sears imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Chronic exposure to cigarette smoke (CS) induces DNA lesions and oxidative damage leading to the development of lung diseases such as emphysema and lung cancer.&nbsp; Xeroderma Pigmentosum group C (XPC) is a protein which repairs CS bulky DNA lesions and oxidative DNA damage, including 8-OHdG.&nbsp; We hypothesize that in vitro CS exposure will result in increased 8-OhdG and that XPC knockdown (KD) leads to higher levels of 8-OHdG.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Methods:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Briefly, immortalized normal human bronchial epithelial cells (Beas2B), were cultured and subsequently exposed to CS extract to induce DNA damage.&nbsp; Cells in agarose were then gently lysed, immersed in an alkaline buffer, incubated with hOGG1 enzyme, and analyzed for DNA damage using single cell electrophoresis (Comet Assay).&nbsp; Slides were stained and viewed by fluorescence microscopy. DNA damage is expressed as tail moment, measured by&nbsp;CometScore. Statistical analysis was performed using 2-way ANOVA (SigmaStat) with p-value &lt; 0.05 indicating statistical significance.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results and Conclusion:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Both XPC KD and wild-type (WT) Beas2B cells treated with 2.5% CS measured higher levels of DNA damage than air control.&nbsp; The addition of hOGG1 lead to an increase in the tail moment in both AC and CS-exposed cells, indicating an increase in the oxidative DNA lesion, 8-OHdG.&nbsp; Finally, XPC KD exposed to 2.5% CS demonstrated an increase in DNA damage and in 8-OHdG compared to WT (p&lt;0.001).&nbsp; In conclusion, these results further support that CS leads to increased oxidative DNA damage and suggests a role for XPC in regulation and repair of the oxidative DNA lesion, 8-OHdG.</p> 2018-12-07T09:32:21-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22670 A Clinically Suitable Approach to Whole-Body Imaging for Quantification of Regional Perfusion: Validation of Positron Emission Tomography (PET) with 62Cu-ETS and Image-based Tracer Kinetic Modeling 2019-01-08T13:22:10-05:00 Monica Cheng imprs@iupui.edu Nathaniel J. Smith imprs@iupui.edu Wendy L. Territo imprs@iupui.edu Carla J. Mathias imprs@iupui.edu James W. Fletcher imprs@iupui.edu Theodore F. Logan imprs@iupui.edu Mark A. Green imprs@iupui.edu Gary D. Hutchins imprs@iupui.edu <p><strong>Background</strong><strong>&nbsp;</strong><strong>&amp;</strong><strong>&nbsp;</strong><strong>Hypothesis:</strong>&nbsp;We hypothesize&nbsp;that&nbsp;whole-body&nbsp;PET imaging&nbsp;with&nbsp;<span data-fontsize="11">62</span>Cu-ETS&nbsp;and readily implemented tracer&nbsp;kinetic&nbsp;models,&nbsp;can&nbsp;enable&nbsp;absolute quantification of regional&nbsp;perfusion&nbsp;(mL•min-1•g-1)&nbsp;in a fashion that&nbsp;is&nbsp;reproducible;&nbsp;readily&nbsp;standardized across institutions;&nbsp;and&nbsp;logistically suitable for&nbsp;clinical&nbsp;implementation.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Experimental Design</strong>:&nbsp;Thirty-five paired&nbsp;<span data-fontsize="11">62</span>Cu-ETS and H<span data-fontsize="11">2</span><span data-fontsize="11">15</span>O studies were performed in&nbsp;six&nbsp;Göttingen&nbsp;minipigs&nbsp;to&nbsp;validate&nbsp;the&nbsp;use of image-derived input functions.&nbsp;H<span data-fontsize="11">2</span><span data-fontsize="11">15</span>O&nbsp;estimates of tissue perfusion&nbsp;served as&nbsp;a reference standard for comparison with&nbsp;<span data-fontsize="11">62</span>Cu-ETS.&nbsp;To demonstrate quantitative whole-body&nbsp;perfusion imaging in humans,&nbsp;paired&nbsp;<span data-fontsize="11">62</span>Cu-ETS and H<span data-fontsize="11">2</span><span data-fontsize="11">15</span>O studies were performed in 14 renal cell carcinoma patients&nbsp;both&nbsp;prior to and following sunitinib therapy.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Results</strong>:&nbsp;The pig studies showed a&nbsp;strong correlation between&nbsp;regional&nbsp;blood flow estimates made with&nbsp;<span data-fontsize="11">62</span>Cu-ETS and&nbsp;H<span data-fontsize="11">2</span><span data-fontsize="11">15</span>O,&nbsp;using&nbsp;image-derived&nbsp;input functions with&nbsp;tracer kinetic model-based corrections for&nbsp;<span data-fontsize="11">62</span>Cu-ETS decomposition in blood&nbsp;(slope=0.932, R<span data-fontsize="11">2</span>=0.746).&nbsp;High quality voxel-wise&nbsp;<span data-fontsize="11">62</span>Cu-ETS perfusion and blood volume parametric images demonstrated a strong correlation with&nbsp;H<span data-fontsize="11">2</span><span data-fontsize="11">15</span>O&nbsp;across all tissues within the imaging field-of-view. Using a same-day test-retest design, which was then repeated&nbsp;across&nbsp;two&nbsp;weeks, the animal&nbsp;study demonstrated good test-retest variability&nbsp;(TRV)&nbsp;for&nbsp;<span data-fontsize="11">62</span>Cu-ETS and&nbsp;H<span data-fontsize="11">2</span><span data-fontsize="11">15</span>O&nbsp;with&nbsp;TRV of 6.3% ± 5.40% and 5.0% ± 4.77%, respectively.&nbsp;These&nbsp;findings strongly support application of the modeling methods to the human data, which is currently in progress.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Conclusion</strong><strong>&nbsp;</strong><strong>&amp;</strong><strong>&nbsp;</strong><strong>Potential Impact</strong>:&nbsp;Whole-body imaging&nbsp;to&nbsp;non-invasively&nbsp;quantify&nbsp;regional perfusion&nbsp;holds&nbsp;promising potential&nbsp;for clinical implementation,&nbsp;using&nbsp;<span data-fontsize="11">62</span>Cu-ETS PET&nbsp;coupled with&nbsp;tracer kinetic models that rely solely on the acquired imaging data.</p> 2018-12-07T09:35:30-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22672 Evaluating the effect of a Participatory Music Program on the Quality of Life and Community Reintegration of Homeless Veterans in Indianapolis 2019-01-08T13:22:09-05:00 Phillip Cheng imprs@iupui.edu Laura Myers imprs@iupui.edu Aimee Lillie imprs@iupui.edu Jennifer Myers imprs@iupui.edu Shannon Crow imprs@iupui.edu Nick Rattray imprs@iupui.edu Sally Wasmuth imprs@iupui.edu Brittany Hook imprs@iupui.edu Ann Lustig imprs@iupui.edu Deb Burns imprs@iupui.edu Dawn Bravata imprs@iupui.edu <p><strong>Background</strong><strong>:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Among Veterans,&nbsp;homelessness is a well-recognized, major problem. Approximately 20% of homeless persons in Indianapolis are Veterans. The Domiciliary Care for Homeless Veterans Program provides residential care for housing insecure Veterans with multiple needs. However, difficulty&nbsp;in&nbsp;combating&nbsp;issues of isolation and&nbsp;lack of avocation&nbsp;for members of the Program&nbsp;remains. Our goal and belief is that providing veterans with&nbsp;a participatory arts&nbsp;will significantly improve their quality of life and reintegration into the community.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Methods:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>This prospective study will use mixed methods to compare intervention participants with usual care controls. Veterans will complete standardized measures including the 20-Item Short Form Health Survey, for quality of life,&nbsp;and Flow State Scale-2,&nbsp;for level of program engagement. Veterans who transition to community housing will complete the Military to Civilian Questionnaire. Veterans will also participate in semi-structured interviews&nbsp;for qualitative data.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Anticipated Results</strong><strong>:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>We anticipate&nbsp;that quality of life will improve among homeless Veterans who participate in the study compared to usual care controls. Further, that we will observe a higher level of community reintegration for participants who leave the Domiciliary.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Significance:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Offering an intervention that looks to change how&nbsp;Veterans&nbsp;see themselves in specific social roles and change how they structure their lives is vital in tackling&nbsp;issues contributing to homelessness.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Potential Impact:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p>This project will provide preliminary data about a participatory music program regarding improvement in quality of life for Veterans with housing insecurity. Findings can be used to build a larger implementation trial across VA&nbsp;domiciliaries&nbsp;nation-wide.</p> 2018-12-07T09:36:08-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22673 Time to Diagnosis of Early-Onset vs. “Late-Onset” Colorectal Cancer: Is there a difference? 2019-01-08T13:22:09-05:00 Kayla L. Chin imprs@iupui.edu Laura E. Myers imprs@iupui.edu Jessica M. Coffing imprs@iupui.edu Jason Larson imprs@iupui.edu Thomas F. Imperiale imprs@iupui.edu <p><strong>BACKGROUND</strong><span data-ccp-props="{}">&nbsp;</span></p> <p>Colorectal cancer (CRC)&nbsp;incidence and mortality&nbsp;is increasing in&nbsp;persons ˂ 50&nbsp;years old. Intervals between symptom onset and initial presentation&nbsp;(presentation interval [PI])&nbsp;and between&nbsp;initial presentation&nbsp;and diagnosis&nbsp;(diagnosis interval [DI])&nbsp;are&nbsp;not well-quantified.<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>OBJECTIVE</strong><span data-ccp-props="{}">&nbsp;</span></p> <p>Compare&nbsp;PI and DI between&nbsp;early-onset CRC&nbsp;(EOCRC) and&nbsp;persons&nbsp;&gt;50, and identify factors affecting these intervals.&nbsp;&nbsp;<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>METHODS</strong><span data-ccp-props="{}">&nbsp;</span></p> <p>In this retrospective VA-based&nbsp;case-control study, we identified EOCRC cases from an ongoing study and compared them to&nbsp;controls (CRC&nbsp;patients&nbsp;aged ≥&nbsp;50 years).&nbsp;We abstracted&nbsp;demographics, clinical features, CRC location and stage,&nbsp;PI, and DI.&nbsp;Mann-Whitney&nbsp;tests compared&nbsp;mean and median PI&nbsp;and DI.&nbsp;<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>RESULTS</strong><span data-ccp-props="{}">&nbsp;</span></p> <p>Advanced stage (III-IV) CRC was more common among&nbsp;the 240&nbsp;EOCRC patients&nbsp;(mean age: 45.2,&nbsp;60.8% White)&nbsp;than in the 234 controls&nbsp;(mean age: 63.8,&nbsp;71.8%&nbsp;White): 55.4% vs&nbsp;43.5%;&nbsp;P= 0.015.&nbsp;PIs and DIs, respectively, were present for 153(63.8%) and 222(92.5%) of cases and for 74(31.6%) 222(94.9%) of controls. No difference was found between median PI in EOCRC and late-onset CRC patients (42 vs 60 days, P= 0.68).&nbsp;The&nbsp;EOCRC cases&nbsp;had&nbsp;a&nbsp;significantly&nbsp;shorter&nbsp;median&nbsp;DI&nbsp;(41 [IQR = 16-83] vs 71 days [IQR = 32-145], P&lt;0.0001).&nbsp;<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>CONCLUSIONS</strong><span data-ccp-props="{}">&nbsp;</span></p> <p>In this retrospective study, younger patients had more advanced stage CRC at diagnosis than their older counterparts. However, contrary to published data, median time to diagnosis was shorter in those &lt; 50&nbsp;years. Factors associated with the DI are forthcoming. Candidate factors include race, diagnosis year, presenting symptoms, type of initial provider, CRC stage, and CRC location.<span data-ccp-props="{}">&nbsp;</span></p> 2018-12-07T09:36:49-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22674 Establishing a Comprehensive Ethics-Based Checklist for Surgical Camp Activities at AMPATH-Kenya 2019-01-08T13:22:09-05:00 Diane B. Choi, BS imprs@iupui.edu Kyle L. Carpenter, MD imprs@iupui.edu Connie H. Keung, MD imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><strong>&nbsp;</strong>Global health has made strides in controlling and reducing harm from infectious diseases such as Polio and HIV/AIDS but&nbsp;this focus has not been mirrored in surgical and anesthesia care, especially in many low and middle-income countries (LMICs). In 2010, an estimated 16.9 million lives were lost from conditions that required surgical care and 5 billion people in LMICs lack safe and affordable surgical and anesthesia.&nbsp;Organization of surgical camps can bring skilled physicians to temporarily meet the unmet surgical needs in underserved areas. However, currently there are no government agencies or accrediting&nbsp;bodies existing to assess the scope/impact of short-term surgical camp care or&nbsp;establish standards of care for such services.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods:</strong><strong>&nbsp;</strong>The AMPATH mission of “start with healthcare and then do more to empower communities, educate tomorrow’s medical experts and research breakthroughs that will truly change the health of the world” was incorporated into the ethical checklist proposed.&nbsp;The&nbsp;four principles – beneficence, non-maleficence, autonomy, and justice were used as guidance&nbsp;for the&nbsp;checklist.&nbsp;<span data-ccp-props="{&quot;134233117&quot;:true,&quot;134233118&quot;:true,&quot;201341983&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><strong>&nbsp;</strong>The checklist can be organized into three main areas: Care, Empowerment &amp; Training, and Research (Figure 1).</p> 2018-12-07T11:11:57-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22675 Assessing generalizability of a new-onset type 1 diabetes Biobank 2019-01-08T13:22:08-05:00 Colette Ciresi imprs@iupui.edu Kathleen Wendholt imprs@iupui.edu Maureen Mullen imprs@iupui.edu Carmella Evans-Molina imprs@iupui.edu Linda DiMeglio imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><strong>&nbsp;</strong><span data-ccp-props="{&quot;134233279&quot;:true,&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Type 1 diabetes (T1D) is characterized by insulin deficiency due to autoimmune pancreatic beta cell destruction. The&nbsp;Wells Center Pediatric Diabetes Research Program&nbsp;is collecting&nbsp;blood and urine samples from children with new onset T1D admitted to Riley Hospital. These samples are being used to discover biomarkers predictive of disease&nbsp;heterogeneity and&nbsp;course. Since not every newly-diagnosed child enrolls in the Biobank, we examined&nbsp;if persons enrolled are similar or different from the at-large population of newly-diagnosed children to know how generalizable samples collected are&nbsp;from our&nbsp;newly-diagnosed population.<span data-ccp-props="{&quot;134233279&quot;:true,&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>P</strong><strong>roject Methods:</strong><strong>&nbsp;</strong>&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Between September 2016 and May 2018, 71 newly-diagnosed children (mean age 9.6±4.3 years) and their caregivers were approached by researchers and asked to provide blood/urine samples. Thirty-four consented/assented (as required); 21 had blood and urine collected; 13 urine only. We looked for differences in age, sex, race, BMI, socioeconomic status (based on zip code), and admission bloodwork parameters between participants and non-participants.&nbsp;<span data-ccp-props="{&quot;134233279&quot;:true,&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><strong>&nbsp;</strong><span data-ccp-props="{&quot;134233279&quot;:true,&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Overall, participants were more likely to be white&nbsp;and have higher admission bicarbonate. Children who provided blood and urine had no other significant differences&nbsp;from&nbsp;non-participants. Children who provided urine only were more likely to be male and to have&nbsp;higher&nbsp;admission bicarbonate than non-participants. Currently, we are obtaining data to make comparisons&nbsp;with the general population of all patients diagnosed at Riley.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion</strong><strong>/</strong><strong>Potential Impact:</strong><span data-ccp-props="{&quot;134233279&quot;:true,&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Our Biobank will provide&nbsp;samples to explore&nbsp;novel biomarkers to facilitate highly-targeted therapies and&nbsp;to&nbsp;screen future preventative treatments. As we continue to collect data, it will remain important to&nbsp;monitor and&nbsp;carefully consider its generalizability.<span data-ccp-props="{&quot;134233279&quot;:true,&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> 2018-12-07T11:14:33-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22676 Role of CaMKK2 in Osteocytes within the Bone Microenvironment 2019-01-08T13:22:08-05:00 Nick Clough imprs@iupui.edu Justin Williams imprs@iupui.edu Uma Sankar imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><strong>&nbsp;</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>The Ca<span data-fontsize="11">+2</span>/calmodulin&nbsp;(CaM)-mediated protein kinase&nbsp;kinase&nbsp;2 (CaMKK2) is a multi-functional kinase with effects on cell proliferation, differentiation and metabolism.&nbsp;The role of CaMKK2 in bone has been explored with its ablation favoring osteoblasts to osteoclasts and bone mass accrual as observed in&nbsp;<em>Camkk2</em><span data-fontsize="11">-/-</span>&nbsp;mice, or following its inhibition&nbsp;by STO-609.&nbsp;One outstanding question is whether the anabolic effects of CaMKK2&nbsp;are bone-cell intrinsic.&nbsp;While analyzing mice harboring bone-cell specific deletion of CaMKK2, we observed a high bone mass phenotype when the kinase is deleted from osteocytes, the most abundant cells within the bone. We therefore hypothesized that the loss of CaMKK2 enhances osteocyte differentiation.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>We used two osteocyte cell lines MLO-Y4 and MLO-A5, both generated from mice expressing the immortalizing T-antigen, to test our hypothesis.&nbsp;The MLO-A5 line has post-osteoblast/pre-osteocyte characteristics while the MLO-Y4 line has mature osteocyte characteristics. CaMKK2 expression was silenced in MLO-A5 cells using Lentiviruses encoding CaMKK2 short hairpin (sh) RNA constructs.&nbsp;STO-609 was employed to inhibit CaMKK2 in the MLO-Y4 line as it proved resistant to transfection. Immunoblotting was used to verify CaMKK2 silencing/inhibition. Comparisons on cell morphologies were observed using immunofluorescence. As osteocytes are defined by dendritic morphology, the number of dendritic processes were analyzed. Additionally, the differences in the expression of the osteocyte markers SOST, E11 and DMP1 were examined by&nbsp;qRT-PCR.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>To be finalized.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p>Overall, our studies will provide more information towards understanding the role of CaMKK2 in bone biology and aid its development as a therapeutic target in the treatment of osteoporosis.</p> 2018-12-07T11:15:23-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22677 Examining Gross Anatomy Study Strategies Across Old and New Curricula 2019-01-08T13:22:08-05:00 Elizabeth Davis, B.A. imprs@iupui.edu Polly R. Husmann, Ph.D. imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><strong>&nbsp;</strong>In the fall of 2016,&nbsp;Indiana University School of Medicine&nbsp;implemented a&nbsp;new integrated&nbsp;curriculum.&nbsp;We hypothesized&nbsp;that the&nbsp;study strategies utilized&nbsp;by students&nbsp;for gross anatomy&nbsp;changed&nbsp;due to this redesign.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Project Methods:</strong><strong>&nbsp;</strong>Students&nbsp;were given&nbsp;a voluntary survey&nbsp;about&nbsp;their study&nbsp;strategies, attitudes, and basic demographics near the end&nbsp;of their anatomy&nbsp;course. The students’&nbsp;NBME&nbsp;and final course scores were&nbsp;also&nbsp;linked to their responses&nbsp;and&nbsp;responses were condensed into&nbsp;categories.&nbsp;Comparisons were made between students in the upper and lower thirds of the classes&nbsp;and between old and new curriculum cohorts.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><strong>&nbsp;</strong>Several differences were found&nbsp;between the old and new curricula: use of web-based resources increased, self-quizzing decreased, and attendance decreased at a statistically significant level&nbsp;(p&lt;0.0001,&nbsp;p=0.042,&nbsp;p&lt;0.0001).&nbsp;Across both curricula, students&nbsp;who&nbsp;were more confident&nbsp;that they had studied enough&nbsp;going into&nbsp;the tests performed more poorly than those who&nbsp;were less confident&nbsp;(p&lt;0.0001).&nbsp;Consistently the&nbsp;students in the top third of the class demonstrated&nbsp;total&nbsp;amounts&nbsp;of study strategies&nbsp;that were&nbsp;lower&nbsp;than&nbsp;in the&nbsp;bottom&nbsp;third of&nbsp;the class, though these results&nbsp;did not reach statistical significance&nbsp;(p=0.382).<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><strong>&nbsp;</strong>Student study&nbsp;strategies&nbsp;have changed between the&nbsp;previous&nbsp;and&nbsp;current&nbsp;anatomy&nbsp;courses&nbsp;in ways that may impact&nbsp;future student outcomes.&nbsp;More use of web-based resources may be of questionable quality and lead to more students feeling overwhelmed,&nbsp;while less&nbsp;self-quizzing&nbsp;may lead to&nbsp;less&nbsp;long-term retention of anatomy content.&nbsp;&nbsp;Metacognitive skills&nbsp;remain vital across curricula.</p> 2018-12-07T11:16:15-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22678 Canines in the emergency department: a novel approach to stress reduction in emergency medicine providers 2019-01-08T13:22:08-05:00 Jacob C. Davis imprs@iupui.edu Kimberly J. Van Ryzin, MD imprs@iupui.edu Courtney T. Linville imprs@iupui.edu Kate L. Pettit, MS imprs@iupui.edu Jeffrey A. Kline, MD imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Cognitive stress during shiftwork contributes to burnout in emergency care. We hypothesize that if&nbsp;emergency care providers (physicians and nurses)&nbsp;were to interact with a therapy dog, their stress levels will decrease.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Consenting&nbsp;emergency&nbsp;medicine physicians and nurses provided&nbsp;three self-reported assessments of stress as well as saliva samples near&nbsp;the beginning&nbsp;of&nbsp;their&nbsp;shift.&nbsp;During peak hours in the&nbsp;emergency department at&nbsp;Eskenazi&nbsp;Hospital&nbsp;participants are randomized to&nbsp;interact with either a therapy dog or perform&nbsp;a&nbsp;mindfulness exercise&nbsp;via&nbsp;art therapy for five minutes.&nbsp;Self-perceived stress and&nbsp;saliva&nbsp;samples&nbsp;are obtained&nbsp;30 minutes&nbsp;later&nbsp;and again near the end of shift.&nbsp;To assess potential change in participant behavior, patients of&nbsp;providers&nbsp;in either group receive a&nbsp;validated&nbsp;questionnaire&nbsp;assessing&nbsp;perceived empathy of the&nbsp;provider.&nbsp;Salivary cortisol will be measured at the end of the study by a vendor (Salimetrics). The sample size of 40 per group is predicated on a 25% decrease in self-reported stress in the dog group&nbsp;on the emergency care worker stress scale (ECWSS).<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>From June 1 to July 10, 24 participants have been randomized (12 in each group).&nbsp;Seven participants (58%) exposed to dogs had a&nbsp;mean&nbsp;decrease in the ECWSS&nbsp;of -5 (+/-1.8)&nbsp;compared with four&nbsp;participants&nbsp;(33%)&nbsp;who had a mean decrease of -2 (+/-0.8)&nbsp;after art therapy.&nbsp;The mean overall change in&nbsp;ECWSS after&nbsp;dog was -2&nbsp;(+/-1.5) vs.&nbsp;+3&nbsp;(+/-1.5) after art therapy.&nbsp;&nbsp;Current&nbsp;data suggest&nbsp;a greater&nbsp;decrease&nbsp;of self-reported&nbsp;stress after interaction with a&nbsp;therapy&nbsp;dog, compared&nbsp;to&nbsp;art therapy.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Interim analysis suggests that exposure to a therapy dog&nbsp;decreases stress in a subset of emergency care workers. This work will help determine if human-animal interaction can modulate stress biology imposed by providing emergency medical care.&nbsp;</p> 2018-12-07T11:17:23-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22679 Skin Sympathetic Nerve Activity and Rate Control of Atrial Fibrillation 2019-01-08T13:22:07-05:00 Anthony Douglas II imprs@iupui.edu Takashi Kusayama, MD, PhD imprs@iupui.edu Peng Sheng Chen, M.D imprs@iupui.edu <p><strong>Background and Hypothesis</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Lifetime risks for&nbsp;atrial fibrillation (AF)&nbsp;are 1 in 4 for&nbsp;people&nbsp;40 years of age and older.&nbsp;Rate and rhythm control are both important strategies in managing patients with AF.&nbsp;However, not all patients respond to beta blocker therapy.&nbsp;We hypothesize that&nbsp;sympathetic tone is important in rate control of&nbsp;AF, but the importance varied among patients.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Experim</strong><strong>ental Design or Project Methods</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>neuECG&nbsp;is a new noninvasive method to record skin sympathetic nerve activity (SKNA) and electrocardiogram.&nbsp;The&nbsp;present research recruited and recorded&nbsp;2&nbsp;paroxysmal and&nbsp;3&nbsp;persistent AF patients for 24 hours&nbsp;using&nbsp;neuECG.&nbsp;The average voltage of SKNA (aSKNA) and ventricular rate during AF was analyzed in one-min windows.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>The preliminary data reveal&nbsp;strong correlations (r=.783,&nbsp;r=.640, respectively,&nbsp;p&lt;0.0001&nbsp;for&nbsp;both) between&nbsp;aSKNA&nbsp;(1.19 ± 0.21&nbsp;µV)&nbsp;and&nbsp;ventricular rate&nbsp;(110 ± 8&nbsp;bpm)&nbsp;in the paroxysmal&nbsp;AF. High correlations were consistently observed when data were analyzed on an hourly basis. In comparison,&nbsp;strong&nbsp;correlations were found&nbsp;between&nbsp;aSKNA&nbsp;(1.13 ± 0.2&nbsp;µV) and&nbsp;ventricular rate&nbsp;(88 ± 8.6&nbsp;bpm)&nbsp;in&nbsp;persistent AF&nbsp;(r=.496,&nbsp;r= .796, r=.636&nbsp;respectively, p&lt;0.001 for both cases).&nbsp;However, hourly correlations&nbsp;displayed much&nbsp;higher&nbsp;variability&nbsp;between&nbsp;aSKNA&nbsp;and&nbsp;ventricular rate&nbsp;than that observed for paroxysmal AF.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact.</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>aSKNA&nbsp;positively correlates with ventricular rate during AF. This relationship is stronger and more consistent during paroxysmal than persistent AF. These findings may be important in&nbsp;determining&nbsp;the&nbsp;efficacy of beta blocker therapy in rate control of AF.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> 2018-12-07T11:18:05-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22680 Determining the cellular localization of C.elegans Editing Enzyme 2019-01-08T13:22:07-05:00 Anna Dudley imprs@iupui.edu Heather Hundley imprs@iupui.edu Suba Rajendren imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p>Over two thirds of human mRNAs contain adenosine(A)-to-inosine (I) editing sites indicating that RNA editing significantly alters the flow of genetic information. RNA editing is required for normal development and proper neuronal function in all animals. Aberrant RNA editing is identified in several neurological disorders and cancers.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p>&nbsp;A-to-I RNA&nbsp;editing is catalyzed by adenosine deaminases that act on RNA (ADARs) proteins. These enzymes commonly bind to double stranded RNA (dsRNA) and catalyze the conversion of adenosine to inosine. However, it is unknown whether these different regions of mRNA are edited by ADARs in the cytoplasm or nucleus. Early research has shown that inosines are present in the nucleus, while new additional evidence shows activity in cytoplasm as well. What dictates the location of the editing is yet unknown.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Experimental Design</strong>:&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p>The subcellular localization of the ADAR editing enzyme will be determined by performing western blots of fractionated&nbsp;<em>Caenorhabditis elegans</em>&nbsp;embryos. Unlike mammals, ADAR editing is not essential in C. elegans, thus making it an easy system to address mechanistic questions about RNA editing. Embryos will be attained from wild-type, ADR-1 and ADR-2 knockout worms, and biochemical techniques will be used to obtain nuclei and cytoplasmic fractions. These fractions will be subjected to SDS-PAGE and western blotting for the ADAR editing enzyme, ADR-2. I will also use positive controls of a nuclear protein (histone) and a cytoplasmic protein (Tubulin) to test the fractionation.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Anticipated Results</strong>:&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p>That there will be more ADR-2 enzyme in the nucleus than the cytoplasm.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Potential Impact:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p>Knowing the location of the edited RNA will allow researchers to have a better idea of what mechanisms influence the editing of ADAR, and what dictates the localization of dsRNA. Current theories involve the number of inosine groups, cellular conditions which effect localization, and nuclear retention molecules other than inosine.&nbsp;</p> 2018-12-07T11:29:21-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22690 Quantitative Effect of Emergency Department Case Management on Visits, Diagnostics, and Cost 2019-01-08T13:22:07-05:00 Jeffrey Nickel, MD imprs@iupui.edu Nancy Connelly imprs@iupui.edu Cameron Duffner imprs@iupui.edu Xyryl Pablo imprs@iupui.edu Aeleia Hughes imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>In 2012, Parkview Health initiated a case management&nbsp;(CM)&nbsp;program&nbsp;with the hypothesis that&nbsp;it&nbsp;would reduce&nbsp;emergency department (ED)&nbsp;visits, radiation exposure, and costs&nbsp;for&nbsp;patients who had visited&nbsp;a&nbsp;Parkview ED&nbsp;5 or more times within 6 months.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>This retrospective case series involved examining&nbsp;medical records of 460&nbsp;CM&nbsp;patients&nbsp;from 2011 to 2018,&nbsp;recording the amount of Parkview ED visits,&nbsp;diagnostic tests, and affected cost accumulated in the year prior to CM enrollment compared to each of the next 2 years.&nbsp;Demographics, chief complaints, diagnoses,&nbsp;psychiatric and drug use history, and whether the patients had insurance&nbsp;and a primary care provider were&nbsp;also recorded.&nbsp;Patient data was&nbsp;excluded&nbsp;if the patient was&nbsp;younger than 18&nbsp;at&nbsp;the&nbsp;time of CM enrollment,&nbsp;had not yet completed&nbsp;2 years in the&nbsp;CM program, or if medical records were not available. ANOVA and&nbsp;1-sided,&nbsp;paired&nbsp;t-testing were performed to&nbsp;evaluate&nbsp;significance of the results.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Comparing&nbsp;the year before&nbsp;enrollment to&nbsp;the 2<span data-fontsize="11">nd</span>&nbsp;year&nbsp;after, ED visits were&nbsp;reduced from 5,264 to 2,012 for 378 patients (63%, p&lt;0.01), the affected cost&nbsp;was reduced from $551,734.45 to $246,248.34&nbsp;for 299 patients&nbsp;(55%, p&lt;0.01),&nbsp;and the number of diagnostic tests was reduced from&nbsp;6,040&nbsp;to 1,883&nbsp;for 104 patients (69%, p&lt;0.01).<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p>Patients enrolled in Parkview’s CM program showed statistically significant reductions in ED visits,&nbsp;radiologic&nbsp;exposures, and affected costs&nbsp;over&nbsp;2 years,&nbsp;with&nbsp;implicit&nbsp;improved health outcomes.&nbsp;Projected 10-year affected cost savings range from $3.7 million to $9.1 million.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559731&quot;:720,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> 2018-12-07T11:30:22-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22691 Lung Ultrasound Proficiency Study 2019-01-08T13:22:06-05:00 Katarina L. Fabre imprs@iupui.edu Frances M. Russell imprs@iupui.edu <p><strong>Background</strong><strong>&nbsp;and Hypothesis</strong><strong>:</strong><strong>&nbsp;</strong>Acute heart failure (AHF) is a major public health burden, and accounts for billions of dollars in healthcare costs annually. Pulmonary congestion is a primary reason patients with AHF seek emergency care. B-lines on lung ultrasound (LUS) is an objective measurement of congestion. It&nbsp;has great implications on diagnosis and&nbsp;prognosis for&nbsp;patients with&nbsp;AHF, but is operator dependent.&nbsp;The goal of this study was to determine if novice sonographers, with limited training, could quantify LUS B-lines with good correlation when compared to experts.<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Methods:&nbsp;</strong>This was a prospective observational study of novice sonographers from three academic institutions. Sonographers received a structured 2-hour ultrasound training on LUS B-line assessment, which included lecture, B-line video review to practice counting, and hands-on patient scanning.&nbsp;Sonographers quantified B-lines in 4 lung zones in each&nbsp;hemithorax&nbsp;in patients with pulmonary edema.&nbsp;The primary objective was measured by comparing novice sonographer B-line counts to a&nbsp;blinded expert&nbsp;reviewer.&nbsp;We used a cumulative sum method for statistical analysis.<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Results</strong><strong>:</strong><strong>&nbsp;</strong>There were xx sonographers, who scanned xx patients with pulmonary edema. We found … (will await Eckert’s stats).&nbsp;<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Conclusion</strong><strong>&nbsp;and&nbsp;</strong><strong>Potential Impact:</strong><strong>&nbsp;</strong>Will await Eckert’s stats<strong>- i</strong>f successful, the&nbsp;quantification&nbsp;of B-lines&nbsp;by novice sonographers in patients with&nbsp;AHF&nbsp;may greatly impact diagnosis, prognosis and risk stratification.<span data-ccp-props="{}">&nbsp;</span></p> 2018-12-07T11:31:44-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22692 Genoproteomic analysis of leukemic cell response to Cytarabine reveals synergistic opportunities centered on cholesterol metabolism 2019-01-08T13:22:06-05:00 Alex Farmer imprs@iupui.edu Fangli Chen imprs@iupui.edu Xue Wu imprs@iupui.edu Adriana Rogozea imprs@iupui.edu Mircea Ivan imprs@iupui.edu Heiko Konig imprs@iupui.edu <p><strong>Background:</strong><strong>&nbsp;</strong>Patients with acute myeloid leukemia (AML) carry&nbsp;a dismal prognosis&nbsp;due&nbsp;to&nbsp;drug resistant&nbsp;cancer cells&nbsp;that reside in O<span data-fontsize="11">2</span>&nbsp;deprived niches of the&nbsp;bone marrow.&nbsp;Here, we&nbsp;sought to&nbsp;interrogate&nbsp;AML drug responses under hypoxic (1% O<span data-fontsize="11">2</span>) and&nbsp;normoxic&nbsp;(21% O<span data-fontsize="11">2</span>) conditions in order to identify novel drug targets.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335551550&quot;:6,&quot;335551620&quot;:6,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Methods:</strong><strong>&nbsp;</strong>We utilized&nbsp;RNAseq, PCR and RPPA&nbsp;to interrogate chemotherapy-induced expression responses&nbsp;in&nbsp;M14 cells.&nbsp;We further assessed&nbsp;intracellular cholesterol&nbsp;levels&nbsp;(ICCLs),&nbsp;cell growth&nbsp;and&nbsp;apoptotic cell death&nbsp;per&nbsp;MTT&nbsp;and FACS analysis in&nbsp;AML cell lines and primary cells&nbsp;(PCs)&nbsp;in response to&nbsp;chemotherapy under&nbsp;normoxia&nbsp;and hypoxia.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335551550&quot;:6,&quot;335551620&quot;:6,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><strong>&nbsp;</strong>Cytarabine&nbsp;blunted&nbsp;cholesterol biosynthesis- and induced CD36-mRNA expression&nbsp;under 1% and 21% O<span data-fontsize="11">2</span>.&nbsp;ICCLs&nbsp;were significantly higher in&nbsp;Cytarabine&nbsp;treated&nbsp;AML&nbsp;cells compared to untreated controls.&nbsp;Treatment with&nbsp;Rosuvastatin&nbsp;significantly inhibited growth of M14, THP1, OCI-AML3 as well as AML&nbsp;PCs&nbsp;(n=3).&nbsp;Further,&nbsp;Rosuvastatin&nbsp;lowered&nbsp;ICCLs&nbsp;and conferred&nbsp;pro-apopotic&nbsp;and growth inhibitory effects against M14 and THP-1 cells. Growth inhibition&nbsp;was&nbsp;enhanced when&nbsp;Rosuvastatin&nbsp;was combined with&nbsp;Cytarabine,&nbsp;yielding&nbsp;additive to synergistic effects.&nbsp;Similar effects were observed in&nbsp;AML&nbsp;PCs&nbsp;(n=10)&nbsp;where&nbsp;Rosuvastatin&nbsp;combined with&nbsp;Cytarabine&nbsp;demonstrated strong synergy.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335551550&quot;:6,&quot;335551620&quot;:6,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion:</strong><strong>&nbsp;</strong>(i)&nbsp;Depletion of&nbsp;ICCLs&nbsp;is counterbalanced by&nbsp;CD36&nbsp;expression&nbsp;in&nbsp;Cytarabine-treated AML cells under&nbsp;normoxia&nbsp;and hypoxia.&nbsp;(ii)&nbsp;Rosuvastatin&nbsp;exerts&nbsp;antileukemic&nbsp;activity in AML cell lines and&nbsp;PCs&nbsp;via downregulation of ICCLs, induction of apoptosis and inhibition&nbsp;of cell growth.&nbsp;(iii)&nbsp;Rosuvastatin&nbsp;acts synergistically&nbsp;with&nbsp;Cytarabine&nbsp;against AML cells.&nbsp;<strong>Impact:&nbsp;</strong>Further investigation of&nbsp;Rosuvastatin&nbsp;&nbsp;in&nbsp;AML therapy&nbsp;is warranted.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335551550&quot;:6,&quot;335551620&quot;:6,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> 2018-12-07T11:32:52-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22693 Aspergeillus Fumigatus: The Effects of Adiponectin on Inflammatory Cytokine Production 2019-01-08T13:22:06-05:00 Rick Foust imprs@iupui.edu Robert Templeton imprs@iupui.edu <p><strong>Background and Hypothesis:&nbsp;</strong>Although inflammatory cytokines are important for antifungal defenses, excessive production significantly increases host immune pathology. It is therefore important to identify host pathways that limit detrimental inflammation in invasive fungal infection. Our prior results showed that mice with invasive&nbsp;aspergillosis&nbsp;(IA) that were deficient in the metabolic cytokine production produced more of the cytokine Tumor Necrosis Factor (TNF) than alveolar in wild-type control mice.&nbsp; Therefore, we hypothesize that adiponectin inhibits antifungal cytokine secretion in alveolar macrophages.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:200,&quot;335559740&quot;:276}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods:&nbsp;</strong>To test this hypothesis, the commonly used A. fumigatus strain Af293 was purchased from the Fungal Genetics Stock Center and grown on and harvested from agar. The alveolar macrophage cell line MH-S and cytokine ELISA kits&nbsp;was&nbsp;obtained from&nbsp;MilliporeSigma&nbsp;and&nbsp;ThermoFisher, respectively. MH-S cells were stimulated with swollen, fixed Af293 conidia for 24 hours in the presence or absence of recombinant mouse adiponectin. After 24 hours, supernatants and cells was were collected and assayed for ILs 1a, 6, and TNF protein and&nbsp;mRNA ,&nbsp;by ELISA and quantitative RT-PCR, respectively.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:200,&quot;335559740&quot;:276}">&nbsp;</span></p> <p><strong>Results:&nbsp;</strong>Although our preliminary results suggest possible inhibition of cytokine secretion by adiponectin in response to&nbsp;<em>A. fumigatus</em>, significant differences have thus far not been observed.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:&nbsp;</strong>We are therefore currently optimizing our experimental conditions to improve antifungal cytokine secretion. These studies may ultimately assist in the discovery of novel therapeutic targets and improve the prognosis of&nbsp;<em>A. fumigatus</em>&nbsp;infections<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:200,&quot;335559740&quot;:276}">&nbsp;</span></p> 2018-12-07T11:33:36-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22696 Assessing Student Engagement and Higher Order Skill Proficiency During the First and Second Year of Medical School – A Comparison Between the Legacy and Recently Reformed Active Learning Curricula 2019-01-08T13:22:05-05:00 Brandon Francis imprs@iupui.edu Mari Hopper, PhD imprs@iupui.edu <p>&nbsp;<strong>Background and Hypothesis:</strong><strong>&nbsp;</strong>This study set-out to determine&nbsp;if:<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <ol> <li data-leveltext="%1." data-font="Arial" data-listid="1" aria-setsize="-1" data-aria-posinset="1" data-aria-level="1">students&nbsp;enrolled in Indiana University’s reformed curricula (RC) demonstrate higher levels of engagement (E) and&nbsp;higher order skill (HOS)&nbsp;proficiency than students&nbsp;prior to reform in the legacy curriculum (LC).&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></li> </ol> <ol> <li data-leveltext="%1." data-font="Arial" data-listid="1" aria-setsize="-1" data-aria-posinset="2" data-aria-level="1">students&nbsp;increase E and HOS&nbsp;from first year of medical school (MS1) to second year (MS2).<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></li> <li data-leveltext="%1." data-font="Arial" data-listid="1" aria-setsize="-1" data-aria-posinset="3" data-aria-level="1">students&nbsp;performing in lowest HOS quartile during MS1 will demonstrate greater gains in HOS by MS2 than students in higher&nbsp;quartiles.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></li> </ol> <p><strong>Experimental Design or Project Methods:</strong><strong>&nbsp;</strong>Determined E&nbsp;using a validated self-report survey (Ahlfeldt, 2007).&nbsp;Assessed HOS&nbsp;using the&nbsp;standardized&nbsp;Collegiate Learning Assessment (CLA+), professionally developed and validated by the Council for Aid to Education (<a href="https://cae.org/flagship-assessments-cla-cwra/cla/">https://cae.org/flagship-assessments-cla-cwra/cla/</a>). Statistical analysis was preliminary; further analysis to be completed by statistician. Between group&nbsp;comparison of LC and RC via t test assuming unequal variance;&nbsp;paired t test for within group&nbsp;comparison&nbsp;MS1 to MS2&nbsp;(significance p&lt;0.05).<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong>&nbsp;Students in RC increased E significantly from MS1&nbsp;(39.0±7.0)&nbsp;to&nbsp;MS2&nbsp;(40.8±5.3)&nbsp;and&nbsp;demonstrate significantly higher&nbsp;E&nbsp;than LC&nbsp;MS2&nbsp;students&nbsp;(36.3±5.3).&nbsp;There were no differences in&nbsp;HOS proficiency&nbsp;when comparing&nbsp;RC to LC, or&nbsp;MS1 to MS2.&nbsp;Students in RC&nbsp;in&nbsp;the lowest&nbsp;quartile for HOS during MS1&nbsp;(1688.8±53.1)&nbsp;significantly&nbsp;increased when re-tested during MS2&nbsp;(1809.5±86.8).<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong>&nbsp;Curricular reform resulted in&nbsp;higher&nbsp;E when compared to LC. Despite&nbsp;increased E, there were no related changes in HOS.&nbsp;Results from quartile analysis agreed with previous&nbsp;reports that active learning preferentially benefits lower performing students&nbsp;(Koles, 2010).</p> 2018-12-07T11:34:19-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22697 Humble But Powerful: The Role of “Access to Information & Knowledge” in Implementation Success in the RE-INSPIRE Study 2019-01-08T13:22:05-05:00 Colin M. E. Fry, M.S. imprs@iupui.edu Edward J. Miech, PhD imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><span data-ccp-props="{&quot;134233279&quot;:true,&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>This study examines&nbsp;the role access to information and knowledge in acute stroke care following a 2011&nbsp;stroke quality improvement clustered randomized trial and a national acute ischemic&nbsp;stroke&nbsp;(AIS) directive in the Veterans Health Administration.&nbsp; Access to information is associated with the highest levels of acute stroke care provision, as well as other key organizational features.<span data-ccp-props="{&quot;134233279&quot;:true,&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods:</strong><span data-ccp-props="{&quot;134233279&quot;:true,&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>A multidisciplinary team analyzed and conducted&nbsp;semistructured&nbsp;interviews of clinical providers across 11 VAMCs over a 3-year period.&nbsp; The interviews were then coded and analyzed using a mix methods approach.&nbsp;This study focused&nbsp;on the “Access to Information and Knowledge” organization feature defined in the Consolidated Framework for Implementation Research constructs.<span data-ccp-props="{&quot;134233279&quot;:true,&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><span data-ccp-props="{&quot;134233279&quot;:true,&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>The manifestations of this organizational feature include: stroke binders, intranet share-points, pocket cards, algorithms, checklists,&nbsp;templates, stroke kits,&nbsp;flow sheets, care&nbsp;maps, posters, and room signs.&nbsp; Acute stroke is a low-volume, high stakes, time sensitive condition at these sites. Therefore,&nbsp;proper access to information is especially important to ensure a continuity of care that transcends the idiosyncrasies of individual providers allowing for&nbsp;quick, correct, and complete care of the patient.<span data-ccp-props="{&quot;134233279&quot;:true,&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><span data-ccp-props="{&quot;134233279&quot;:true,&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>The mere presence of certain tools in a clinical setting is not enough, but rather the feature relies on getting the right information, to the right people, at the right time.&nbsp;&nbsp;Access to information&nbsp;exemplifies the need for&nbsp;implementation science, and insights from this study can be broadly applied to a plethora of scenarios in other clinical settings.</p> 2018-12-07T11:35:31-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22698 Effect of Frataxin Knockout on Mouse Cardiomyocytes Using DsRed.T3 as a Quantifying Marker 2019-01-08T13:22:05-05:00 Eric Galante imprs@iupui.edu P Melanie Pride imprs@iupui.edu Frances Chen, MD imprs@iupui.edu R Mark Payne, MD imprs@iupui.edu <p><strong>Background and Hypothesis:&nbsp;</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Discosoma&nbsp;Red (DsRed)&nbsp;is a&nbsp;strong&nbsp;fluorescent marker that has many practical uses for scientific studies.&nbsp;We engineered a transgenic mouse expressing DsRed.T3 only in cardiomyocyte nuclei, and then crossed this with a conditional knockout mouse with loss of Frataxin (FXN) in heart.&nbsp;It is known that dysfunction&nbsp;of&nbsp;the Frataxin (FXN) gene can cause Friedrich’s Ataxia (FRDA), a disease associated with ataxia, weakness and dilated cardiomyopathy in humans. The current study aimed to: 1) Determine if&nbsp;DsRed&nbsp;overexpression in cardiomyocyte nuclei&nbsp;would negatively affect cardiac tissue, and 2)&nbsp;Use the&nbsp;DsRed.T3 mouse&nbsp;to&nbsp;determine&nbsp;whether FXN knockout (KO) would cause a loss of cardiomyocytes.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods:&nbsp;</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>The study was done by examining three different strains of mice: wild-type, DsRed.T.3&nbsp;overexpressing Tg mice, and FXN KO mice with loss of FXN in cardiomyocytes.&nbsp;Mice were analyzed using&nbsp;genotyping, frozen immunofluorescent stains,&nbsp;α-actinin and Hoechst, TPLSM, confocal microscopy, western blotting, H&amp;E, echocardiography, and&nbsp;heart:body&nbsp;weight ratios.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:&nbsp;</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Results showed that DsRed.T3&nbsp;localized to the nucleus of cardiomyocytes&nbsp;and that after 6.5 months there&nbsp;were&nbsp;some significant effects on cardiac function, although not on cardiac tissue. Further analysis&nbsp;is ongoing to determine if there is&nbsp;a&nbsp;loss of&nbsp;cardiomyocytes within the FXN KO group.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>This study shows promise for how researchers can study the heart, and more specifically, Friedreich’s Ataxia, while also shedding light on how FXN may ultimately affect the heart in FRDA patients.</p> 2018-12-07T11:39:55-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22699 Is Liver Function Homogenous? Correlation between CT Liver Volumes and Liver Function as Determined by Functional Hepatobiliary (HIDA) Scan 2019-01-08T13:22:05-05:00 Jarrell G. Gary, MS imprs@iupui.edu Paul Haste, MD imprs@iupui.edu Mark Tann, MD imprs@iupui.edu <p><strong>Background</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p>A hepatobiliary (HIDA) scan is a&nbsp;study historically done to evaluate for cholecystitis&nbsp;and more recently shown to be&nbsp;an&nbsp;effective&nbsp;way to&nbsp;measure liver function.&nbsp;Volumetric analysis on computed tomography (CT) is the most common way&nbsp;to evaluate future liver remnant prior to planned&nbsp;partial&nbsp;hepatectomy&nbsp;or radiation therapy.&nbsp;The aim of this study is to determine&nbsp;to what degree&nbsp;do&nbsp;lobar&nbsp;CT&nbsp;volume ratios correlate with&nbsp;distribution of&nbsp;functionality.&nbsp;&nbsp;&nbsp;&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Experimental Design</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p>A retrospective review and analysis&nbsp;of the images for 63&nbsp;patients with liver cancer,&nbsp;imaged between&nbsp;2016 and 2018,&nbsp;was performed. All functional HIDA scans&nbsp;were&nbsp;processed&nbsp;using MIM software. Total liver function, with lobar ratios,&nbsp;were&nbsp;obtained.&nbsp;Whole liver and lobar volume analysis on CT was also performed.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Result</strong><strong>s</strong><strong>&nbsp;</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p>The mean age was 63.6&nbsp;[Symbol]&nbsp;11.0 years with a male to female ratio of 1.3:1. The mean total liver volume on CT was 1611.3&nbsp;[Symbol]&nbsp;590.5 mL (Right lobe:&nbsp;961.5&nbsp;[Symbol]&nbsp;405.3&nbsp;mL, Left lobe:&nbsp;649.8&nbsp;[Symbol]&nbsp;331.7&nbsp;mL). The mean ratio of right to left lobar volumes was 59.5&nbsp;[Symbol]&nbsp;13.5 % to 40.6&nbsp;[Symbol]&nbsp;13.5%. The mean ratio of right to left lobar liver function was&nbsp;60.7&nbsp;[Symbol]&nbsp;20.7% to 39.5&nbsp;[Symbol]&nbsp;21.1%.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p>The overall average ratio between right and left lobe liver function appears to closely relate to the&nbsp;volumetric ratio between the lobes. These&nbsp;promising results suggest that liver function is fairly homogenous, which&nbsp;could provide&nbsp;great value in planning future liver operations and radiation therapy.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> 2018-12-07T11:40:45-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22713 Marginal Utility of Additional Clinical Shifts on Milestone-Based Competency in an Emergency Medicine Clerkship 2019-01-08T13:22:04-05:00 Rolando G Gerena imprs@iupui.edu Nash Whitaker imprs@iupui.edu Dan Corson-Knowles imprs@iupui.edu <p><strong>Background</strong><strong>:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Emergency medicine clerkships are a required element of medical school programs. The optimal rotation structure&nbsp;is unknown, and in particular&nbsp;the number of clinical shifts required to achieve basic competency is unknown. In this analysis of one year of evaluations at an academic center,&nbsp;we assess the marginal utility of&nbsp;clinical shifts on competency, as assessed by historical preceptor milestone-based competency evaluations.  <span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>The goal of the experiment is to observe the trend of passing rates throughout the course of an EM rotation using&nbsp;competencies&nbsp;including&nbsp;medical knowledge, data interpretation, and clinical judgement.&nbsp;The null hypothesis is that the percentage of students meeting the&nbsp;developmental&nbsp;milestones&nbsp;does not increase throughout the&nbsp;length&nbsp;of the&nbsp;clerkship.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Methods:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Clerkship evaluations of 200&nbsp;students were&nbsp;retrospectively&nbsp;examined.&nbsp;A short form grading rubric was used to score students across eight developmental milestones.&nbsp;The&nbsp;average percentage of&nbsp;students&nbsp;meeting the developmental milestones&nbsp;were&nbsp;calculated and analyzed&nbsp;over the course of 14 shifts.&nbsp;A&nbsp;one-way&nbsp;ANOVA&nbsp;was&nbsp;used to compare the mean passing rates at different times&nbsp;of&nbsp;the clerkship.&nbsp;&nbsp;&nbsp;&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Results:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>The average&nbsp;percent&nbsp;of students&nbsp;achieving basic competency increased throughout the&nbsp;length&nbsp;of the clerkship, e.g.&nbsp;medical knowledge&nbsp;competency passing rates increased from&nbsp;44.2% to 56.0%,&nbsp;first to last shifts respectively.&nbsp;Similar trends were observed in&nbsp;other competencies.&nbsp;The&nbsp;one-way ANOVA&nbsp;gave a p-value of&nbsp;less than&nbsp;0.05;&nbsp;the null hypothesis was rejected.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion/</strong><strong>Potential Impact:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p>The results can&nbsp;aid&nbsp;clerkship&nbsp;directors improve&nbsp;current grading&nbsp;rubrics&nbsp;to better assess student competency in their&nbsp;EM&nbsp;clerkships.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> 2018-12-07T12:01:58-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22701 Medical Students’ Studying Approach to a Changing Medical School Anatomy Curriculum 2019-01-08T13:22:04-05:00 Daniel Gibson, BA imprs@iupui.edu Polly Husmann, PhD imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>With&nbsp;medical school&nbsp;curriculum changes,&nbsp;students&nbsp;have&nbsp;to&nbsp;reassess&nbsp;how they approach their studies.&nbsp;This&nbsp;study evaluates how medical students planned to&nbsp;study gross anatomy before and after the&nbsp;2016&nbsp;Indiana University School of Medicine (IUSM)&nbsp;curriculum change.&nbsp;Student study plans are hypothesized&nbsp;to be different before and after the curriculum change.&nbsp;&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Methods:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>First-year medical students&nbsp;from&nbsp;2015-2017&nbsp;were given a&nbsp;survey&nbsp;prior to&nbsp;their&nbsp;gross anatomy course.&nbsp;The survey integrated&nbsp;37&nbsp;Likert scale questions about&nbsp;resources the students might use, study&nbsp;strategies,&nbsp;demographics, prior anatomy and/or physiology courses,&nbsp;etc.&nbsp;T-tests were run between&nbsp;the&nbsp;curriculum and&nbsp;student&nbsp;grades&nbsp;as well as&nbsp;seven categories that grouped related questions from the survey.&nbsp; Comparisons were also made between the upper and lower thirds of the class.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>The final course and NMBE percentages were found to be significantly different&nbsp;between curricula&nbsp;(p&lt;0.0001/p&lt;0.0001).&nbsp;Differences in&nbsp;planned usage of&nbsp;text-based, lab-based, and web-based resources were also&nbsp;significant&nbsp;(p&lt;0.0001/p=0.002/p=0.007).&nbsp;Analyses&nbsp;additionally&nbsp;found&nbsp;that&nbsp;students in the&nbsp;upper third of all classes&nbsp;were more likely to have a prior anatomy and physiology course&nbsp;(p=0.031).<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Student study plans for anatomy have changed with the revision of the curriculum.&nbsp; Current students are planning to use outside resources (e.g., textbooks, websites) more than previous cohorts in the traditional curriculum.&nbsp; In addition, students with prior knowledge of anatomy and physiology may have an advantage in understanding medical anatomy.&nbsp; These findings have implications for the long-term retention of this material and&nbsp;subsequent&nbsp;student outcomes.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> 2018-12-07T12:03:03-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22714 Developmental Toxicity of TCE Exposure in Zebrafish: Analyzing Vitamin D Metabolism 2019-01-08T13:22:04-05:00 Briana M. Grisby imprs@iupui.edu Kathryn M. Thompson imprs@iupui.edu Jennifer L. Freeman imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><strong>&nbsp;</strong>Trichloroethylene (TCE) is an industrial solvent used since the 1940s. A known carcinogen, it is found in over half of Superfund sites where levels have reached 12,000 parts per billion (ppb; µg/L), though the US Environmental Protection Agency maximum contaminant level in drinking water is 5 ppb. In this study, the zebrafish model was used to investigate the developmental toxicity of TCE by assessing its effects on metabolism. Preliminary studies have shown a reduction in gene expression of the cytochrome P450 (CYP) enzymes responsible for breakdown of vitamin D. As a result, we expected to see lower levels of downstream metabolites, namely calcitriol, as detected by an Enzyme-Linked Immunosorbent Assay (ELISA).<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335551550&quot;:6,&quot;335551620&quot;:6,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design</strong><strong>:</strong><strong>&nbsp;</strong>At 0-2 hours post fertilization (hpf), embryos were dosed with TCE at either 0 or 10 ppb. At 72 hpf, the larvae were removed from the TCE and prepared for the ELISA procedure.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335551550&quot;:6,&quot;335551620&quot;:6,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong>&nbsp;ELISA revealed similar levels of calcitriol between the control and 10 ppb groups. The difference between the two groups did not show statistical significance&nbsp;(p&gt;0.05).<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335551550&quot;:6,&quot;335551620&quot;:6,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion:</strong>&nbsp;These results suggest that&nbsp;there may not be a direct relationship between CYP gene expression and certain downstream metabolic effects&nbsp;or that the organism was able to compensate for the biological changes.&nbsp;If the latter, additional time points for TCE exposure could be evaluated.&nbsp;As studies continue, we&nbsp;plan&nbsp;to evaluate CYP gene expression at higher concentrations to correlate with other biological effects and determine if there is consistency with results from lower concentrations.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335551550&quot;:6,&quot;335551620&quot;:6,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> 2018-12-07T12:03:42-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22703 Characterizing the Extent of Cell Death in Innate Immune Mediated Colitis 2019-01-08T13:22:03-05:00 Justin R. Hendrix imprs@iupui.edu Anne-Marie Overstreet imprs@iupui.edu Antonia Boger-May imprs@iupui.edu David Boone imprs@iupui.edu <p><strong>Background</strong><strong>&nbsp;and Hypothesis</strong><strong>:</strong><strong>&nbsp;</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Intestinal epithelial cell (IEC) turnover occurs every four-to-five days.&nbsp;In inflammatory bowel disease (IBD), IECs undergo increased&nbsp;cell death due to&nbsp;inflammation of intestinal villi and colonic crypts.&nbsp;This cell death&nbsp;leads to increased permeability of the intestinal barrier.&nbsp;This study&nbsp;examined the pathogenesis&nbsp;of&nbsp;IBD,&nbsp;focusing&nbsp;on innate immunity&nbsp;using&nbsp;mice&nbsp;with&nbsp;spontaneous innate immune colitis.&nbsp;The&nbsp;objective was&nbsp;to observe if&nbsp;there is a significant difference in&nbsp;expression of apoptosis in&nbsp;colitic&nbsp;mice&nbsp;vs.&nbsp;control&nbsp;mice.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design</strong><strong>:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Mice expressing the NF-kB inhibitor TNFAIP3 in&nbsp;the villi of&nbsp;IECs&nbsp;were interbred&nbsp;with&nbsp;RAG1<span data-fontsize="11">-/-</span>&nbsp;mice. TNFAIP3 x RAG1<span data-fontsize="11">-/-</span>&nbsp;(TRAG) mice developed 100% penetrant colitis by 6 weeks of age that was not observed&nbsp;in TNFAIP3 or RAG1<span data-fontsize="11">-/-</span>&nbsp;littermates.&nbsp;The&nbsp;presence&nbsp;of activated&nbsp;caspase-3&nbsp;in distal colons was detected&nbsp;using&nbsp;immunofluorescence&nbsp;and&nbsp;quantified using ImageJ to compare differences between 4-&nbsp;and&nbsp;8-week-old&nbsp;RAG&nbsp;vs.TRAG&nbsp;mice.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Increased&nbsp;numbers&nbsp;of caspase-3<span data-fontsize="11">+</span>&nbsp;cells&nbsp;were found in&nbsp;TRAG mice&nbsp;compared to RAG mice.&nbsp;After treatment with antibiotics, similar levels of&nbsp;capase-3 were detected in both groups.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion</strong><strong>&nbsp;and Potential Impact</strong><strong>:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>This investigation suggests that cell death in TRAG mice were&nbsp;increased due to deficient innate immunity in IECs.&nbsp;Thus,&nbsp;bacteria play a direct role by killing IECs or an indirect role by causing inflammation.&nbsp;Understanding&nbsp;how innate immune&nbsp;activation&nbsp;drives cell death in IECs,&nbsp;may lead to a better&nbsp;understanding of the complex regulation&nbsp;of&nbsp;IBD, and improved&nbsp;therapeutic agents&nbsp;targeting&nbsp;novel cell types in the remission of&nbsp;chronic IBD.&nbsp;</p> 2018-12-07T12:04:14-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22704 Assessing lead exposure sources at the property scale in Indianapolis 2019-01-08T13:22:03-05:00 Emily Hentz, BS imprs@iupui.edu Gabriel Filippelli, PhD imprs@iupui.edu Noah Springer imprs@iupui.edu Emily Hopkins, MA, BS, BA imprs@iupui.edu Isheka Orr imprs@iupui.edu Rachel Smith, BA imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Lead (Pb) was phased out of&nbsp;paint and&nbsp;gasoline&nbsp;over 40 years ago&nbsp;due to&nbsp;neurotoxicity in humans, but&nbsp;has&nbsp;persisted&nbsp;in soils&nbsp;and&nbsp;poses a&nbsp;legacy&nbsp;threat to many.&nbsp;&nbsp;The&nbsp;Indianapolis&nbsp;46218 zip code&nbsp;has had&nbsp;&gt;10%&nbsp;children exhibiting&nbsp;Pb&nbsp;poisoning.&nbsp;This zip code has had historically high&nbsp;soil&nbsp;Pb&nbsp;levels,&nbsp;and is&nbsp;undergoing&nbsp;redevelopment.&nbsp;We hypothesize that redevelopment will act to re-expose new&nbsp;populations&nbsp;of people to the legacy&nbsp;Pb&nbsp;present in the area.&nbsp;&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>We sampled&nbsp;5&nbsp;parks and&nbsp;7&nbsp;playgrounds.&nbsp;&nbsp;Stratified random sampling based on permit type&nbsp;was&nbsp;used to select&nbsp;properties from&nbsp;25 issued and&nbsp;25&nbsp;closed permits&nbsp;from&nbsp;527 identified demolition permits.&nbsp;&nbsp;Nearby residential properties&nbsp;were selected, with&nbsp;permission of residents.&nbsp;Samples&nbsp;were taken near the dripline of the house, front yard, and&nbsp;street,&nbsp;or&nbsp;from each quadrant&nbsp;at sites without&nbsp;houses.&nbsp;Samples were dried, crushed,&nbsp;sieved&nbsp;to 150 microns, and&nbsp;assessed using X-Ray&nbsp;Fluorescence.&nbsp;&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Mean&nbsp;Pb&nbsp;levels&nbsp;from driplines (1026&nbsp;ppm) were significantly higher than&nbsp;streets&nbsp;(p=0.001), parks (p=0.002),&nbsp;yards (p=0.001),&nbsp;and demolition sites&nbsp;(p=0.000).&nbsp;&nbsp;Pb&nbsp;concentrations for&nbsp;playgrounds had the lowest&nbsp;median lead levels (42&nbsp;ppm), while dripline samples had the&nbsp;highest&nbsp;(289 ppm).&nbsp;&nbsp;The&nbsp;EPA standard for children’s play areas is 400 ppm.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p>While&nbsp;all samples from playgrounds were below&nbsp;400 ppm,&nbsp;children are also likely&nbsp;playing at their homes,&nbsp;where no legislation&nbsp;effectively protects&nbsp;them from potential&nbsp;Pb&nbsp;poisoning&nbsp;and values were found above 400 ppm.&nbsp;&nbsp;An&nbsp;immediate outcome from this project is the education.&nbsp; Residents who agreed&nbsp;to testing (n=42) received&nbsp;results of the test&nbsp;and&nbsp;guidelines to prevent&nbsp;Pb&nbsp;poisoning.&nbsp;&nbsp;More work remains to ensure&nbsp;preventive rather than reactive strategies are employed to protect children’s health.</p> 2018-12-07T12:04:48-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22705 Is Operative Diagnosis for Revision Total Hip Arthroplasty Related to Patient Reported Outcomes? 2019-01-08T13:22:03-05:00 Erik Holder, BA, BS imprs@iupui.edu Alex Ciesielski, BS imprs@iupui.edu Mary Ziemba-Davis, BA imprs@iupui.edu R. Michael Meneghini, MD imprs@iupui.edu <p><strong>Background</strong><strong>&nbsp;and Hypothesis</strong>:&nbsp;&nbsp;Component loosening&nbsp;and&nbsp;instability are the leading causes of revision total hip arthroplasty (THA).&nbsp;The purpose of this study&nbsp;was&nbsp;to compare&nbsp;patient-reported&nbsp;outcomes after revision THA based on failure etiology.&nbsp;We hypothesized that outcomes would&nbsp;differ&nbsp;based&nbsp;on reason for revision.</p> <p><strong>Project Methods</strong>: 187 consecutive revision THAs performed between 2010 and 2017 were retrospectively reviewed.&nbsp;Prospectively collected&nbsp;preoperative and minimum one-year Hip Disability and Osteoarthritis Outcome Score/HOOS Jr.,&nbsp;UCLA Activity Level,&nbsp;WOMAC Index,&nbsp;and&nbsp;patient&nbsp;satisfaction were assessed based on failure etiology.&nbsp;&nbsp;Demographic variables and covariates were accounted for&nbsp;including sex, age, BMI, ASA&nbsp;classification, heart disease, lumbar spine pathology,&nbsp;narcotic&nbsp;use, fibromyalgia, depression, and autoimmune&nbsp;arthritis.&nbsp;<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Results</strong>:&nbsp;Latest UCLA activity level did not differ based on&nbsp;failure etiology (<em>p</em>=0.381). However,&nbsp;the degree of improvement in activity level&nbsp;was&nbsp;higher&nbsp;(<em>p</em>= 0.04) in patients revised for&nbsp;loosening, instability,&nbsp;and infection compared to ALTR&nbsp;and polyethylene wear.&nbsp;HOOS Jr&nbsp;(<em>p</em>=0.949)&nbsp;and&nbsp;WOMAC total (<em>p</em>=0.147) scores&nbsp;did not differ based on&nbsp;failure etiology at latest follow-up,&nbsp;although&nbsp;patients revised for loosening had greater&nbsp;WOMAC&nbsp;improvement&nbsp;compared to all other&nbsp;groups except&nbsp;polyethylene&nbsp;wear&nbsp;(<em>p</em>=0.016).&nbsp;Satisfaction&nbsp;did not vary based on failure etiology&nbsp;(<em>p</em>=0.365), and demographic and covariates were unrelated to outcomes (<em>p</em>[Symbol]0.165).&nbsp;&nbsp;<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Conclusion and Potential&nbsp;</strong><strong>Impact</strong>:&nbsp;We observed that patient-reported outcomes following revision THA vary based on revision reason&nbsp;and activity level improvement is mitigated patients revised for ALTR and poly wear.&nbsp; These&nbsp;findings may help surgeons and&nbsp;patients alike set expectations for recovery following revision THA.&nbsp;&nbsp;<span data-ccp-props="{}">&nbsp;</span></p> 2018-12-07T12:05:26-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22706 Fat Soluble Vitamin, B12 and Iron Deficiency in Patients with Coliform Small Intestinal Bacterial Overgrowth (SIBO) 2019-01-08T13:22:02-05:00 Gage Howard imprs@iupui.edu John Wo imprs@iupui.edu <p><strong>Background and Hypothesis:</strong>&nbsp;Vitamin deficiency has been described as a clinical complication of SIBO. However, it is unclear if the type of bacterial colonization is an important determinant in vitamin and nutritional complications. Our aim was to&nbsp;characterize the&nbsp;prevalence of specific vitamin and mineral deficiencies (vitamins A, D, E, K, B12, and iron) in patients with and without coliform SIBO. We hypothesized that&nbsp;results would show a significant&nbsp;increase&nbsp;in the incidence of&nbsp;vitamin and/or mineral deficiency in patients with coliform SIBO.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Methods:</strong>&nbsp;A prospective registry was formulated, consisting of patients presenting to our outpatient motility clinic with suspected SIBO. Serum levels of vitamins A, D, E, INR for K, B12 and iron studies were obtained. Upper enteroscopy-aspiration and quantitative aerobic-anaerobic cultures were performed. Primary study endpoints were prevalences of&nbsp;clinical vitamin/mineral deficiencies&nbsp;(A, D, E, K, B12, and iron)&nbsp;based on the final diagnosis: A) SIBO by coliform bacteria (&gt;10<span data-fontsize="11">4</span>&nbsp;CFU/mL), B) SIBO by upper respiratory tract (URT) bacteria (&gt;10<span data-fontsize="11">5</span>&nbsp;CFU/mL) and no SIBO. 2x3 chi square, univariate and multivariate analyses were utilized.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Expected Results:</strong>&nbsp;128 subjects were enrolled, and 96 subjects underwent aspiration. Final diagnoses were the following: coliform SIBO in 32 (33%) and no SIBO or URT SIBO in 64 (67%). The presence of any vitamin deficiency appears to be more prevalent in patients with coliform SIBO (46.7%) than those without (28.1%), but it is currently unclear&nbsp;if&nbsp;these differences reach statistical significance.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Conclusions:</strong>&nbsp;1) Fat-soluble vitamin deficiency may be more common in coliform SIBO, but its absence does not exclude the possibility of coliform SIBO being present. 2) Although a high folate and low B12 can be suggestive of SIBO, these derangements were not common in our heterogeneous group of patients.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>*</strong>Will send update following data analysis*</p> 2018-12-07T12:59:39-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22707 A Bioinformatics Pipeline for Identifying Functional Explanations of SNP-Phenotype Associations on a Transcriptional Level 2019-01-08T13:22:02-05:00 Stephan Hu imprs@iupui.edu Dr. Xi Rao imprs@iupui.edu Dr. Yunlong Liu imprs@iupui.edu <p><strong>Background and Hypothesis</strong>:&nbsp;Genome-wide association studies (GWAS) have identified thousands of associations between single nucleotide polymorphisms (SNP) and traits of interest.&nbsp;These&nbsp;associations do not offer biological or functional explanations for differences in phenotype.&nbsp;This study works on filling the gap between these associations and their functional effect on phenotype by identifying variants that are associated due, at least in part, to their effect on&nbsp;a&nbsp;transcriptional level.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods:</strong><strong>&nbsp;</strong>GWAS analysis and RNA-sequencing was run on the post-mortem brain tissue of heavy drinkers and non-drinkers. Genes that were associated with differential transcript production were&nbsp;overlaid with chromatin interaction data to identify potential enhancers. A number of properties of enhancers were used to narrow down the list.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><strong>&nbsp;</strong>Identified enhancers offer a potential functional explanation for the association between a SNP and trait.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><strong>&nbsp;</strong>This new technique offers a powerful tool to identify genetic variants in key regulatory regions. Although here it is used for an alcohol use disorder study, this protocol has the potential to be used in a wide range&nbsp;of statistical genomic settings to find functional explanations for associations between SNP and trait.</p> 2018-12-07T13:02:16-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22715 Tendon transfer of pronator teres to flexor pollicis longus to restore thumb flexion in incomplete tetraplegia 2019-01-08T13:22:02-05:00 Nathan P. Jarrett imprs@iupui.edu Gregory A. Merrell imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><strong>&nbsp;</strong>Incomplete tetraplegia creates immense barriers to autonomy for individuals with spinal cord injuries. These patients may retain control of some forearm extensors, but use of flexors is largely eliminated, affecting&nbsp;many&nbsp;movements necessary for daily activities. Although tendon transfers using brachioradialis and other muscles to restore hand function are standard practice, pronator teres has not&nbsp;been extensively studied as a&nbsp;donor&nbsp;for flexors. The purpose of this study is to quantify forearm pronation capability pre- and post-tendon transfer of pronator teres to flexor pollicis longus in a cadaver model.&nbsp;We hypothesize that tendon&nbsp;transfer will make thumb flexion possible, while&nbsp;preserving forearm pronation&nbsp;against gravity&nbsp;at&nbsp;a&nbsp;minimum.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Experimental Design:</strong><strong>&nbsp;</strong>Five cadaver arms were evaluated for&nbsp;pronation capability&nbsp;against gravity&nbsp;before and after tendon transfer. In&nbsp;both&nbsp;stages, the arms were also&nbsp;assessed for&nbsp;the pronation forces produced at the wrist when&nbsp;pulling&nbsp;pronator teres with 25, 50, and 75 N of force.&nbsp;With each force,&nbsp;the arms were&nbsp;tested in&nbsp;full supination&nbsp;and&nbsp;neutral&nbsp;position.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><strong>&nbsp;</strong>All five arms were capable of pronating against gravity before and after the tendon transfer. Following the transfer, pronation force decreased,&nbsp;but&nbsp;the difference was&nbsp;not statistically significant.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><strong>&nbsp;</strong>Pronator teres to flexor pollicis longus tendon transfer produces thumb flexion while retaining the forearm’s ability to pronate. Used in conjunction with well-established donors, such as brachioradialis, pronator teres’ expendability&nbsp;could offer&nbsp;an additional motor unit for restoring hand function&nbsp;in tetraplegic patients.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> 2018-12-07T13:03:08-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22716 Blueberry containing diets protect from bone loss induced by sex steroid deficiency differently depending on sex and by mechanisms independent of canonical sex steroid receptor signaling 2019-01-08T13:22:02-05:00 O R Johnson imprs@iupui.edu A Y Sato imprs@iupui.edu G G Pellegrini imprs@iupui.edu M Cregor imprs@iupui.edu K McAndrews imprs@iupui.edu E Atkinson imprs@iupui.edu R B Choi imprs@iupui.edu M Maiz imprs@iupui.edu L D McCabe imprs@iupui.edu G P McCabe imprs@iupui.edu M Peacock imprs@iupui.edu C M Weaver imprs@iupui.edu D Burr imprs@iupui.edu T Bellido imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>There is an unmet need for&nbsp;interventions that&nbsp;prevent&nbsp;bone loss induced by sex steroid deficiency.&nbsp;Loss of estrogens or androgens&nbsp;increases&nbsp;ROS&nbsp;in bone.&nbsp;We&nbsp;hypothesized that&nbsp;diets&nbsp;containing blueberries with antioxidant&nbsp;properties&nbsp;would&nbsp;protect from bone loss induced by&nbsp;sex steroid&nbsp;deficiency, depending&nbsp;on&nbsp;sex and on the expression of&nbsp;Nrf2, a transcription factor that regulates the endogenous antioxidant response.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>SHAM,&nbsp;ovariectomized&nbsp;(OVX), or&nbsp;orchidectomized&nbsp;(ORX)&nbsp;4-month-old,&nbsp;wild type&nbsp;(WT) or Nrf2 knockout&nbsp;(KO)&nbsp;male and female&nbsp;mice&nbsp;were fed&nbsp;with&nbsp;control&nbsp;diet&nbsp;or&nbsp;diets containing&nbsp;3 types of blueberries.&nbsp;Bone mineral density (BMD) and bone microarchitecture were measured by dual-energy x-ray absorptiometry&nbsp;and microscopic computed tomography, respectively; and gene expression was quantified in bone RNA&nbsp;by quantitative&nbsp;PCR.&nbsp;&nbsp;&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Control-fed&nbsp;OVX&nbsp;or ORX&nbsp;mice exhibited&nbsp;the expected&nbsp;BMD&nbsp;loss,&nbsp;to&nbsp;a similar&nbsp;extent,&nbsp;in&nbsp;WT and KO mice.&nbsp;One of the blueberry diets (Montgomery)&nbsp;prevented bone loss,&nbsp;totally in females&nbsp;and partially in males; and&nbsp;prevented&nbsp;~50%&nbsp;of&nbsp;microarchitecture deterioration in ORX mice,&nbsp;independently of Nrf2 expression.&nbsp;OVX&nbsp;and ORX&nbsp;decreased expression of&nbsp;estrogen-response-element gene C3&nbsp;or&nbsp;androgen-response-element&nbsp;gene Rhox5, respectively,&nbsp;in both&nbsp;WT and KO mice fed&nbsp;control or Montgomery&nbsp;diets, indicating that bone protection is not due to estrogenic/androgenic actions&nbsp;of the diet.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Montgomery diet prevented bone loss due to sex steroid deficiency fully in females&nbsp;and partially in males. Thus,&nbsp;optimal skeletal benefits&nbsp;might&nbsp;be&nbsp;achieved&nbsp;by tailoring&nbsp;antioxidant-rich diets to patients of either sex.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> 2018-12-07T13:06:58-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22717 Leukocyte Localization in a Model of Innate Immune-Driven Colitis 2019-01-08T13:22:01-05:00 Jordan R. Jones imprs@iupui.edu Anne-Marie C. Overstreet imprs@iupui.edu Antonia M. Boger-May imprs@iupui.edu David L. Boone imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Inflammatory bowel disease (IBD) is a&nbsp;disabling, chronic&nbsp;gut disorder&nbsp;involving immune&nbsp;dysregulation.&nbsp;Our&nbsp;lab&nbsp;has&nbsp;generated&nbsp;a murine IBD model&nbsp;in which&nbsp;the innate immune system&nbsp;drives inflammation.&nbsp;Innate lymphoid cells (ILCs), an&nbsp;innate immune&nbsp;cell&nbsp;subset&nbsp;that was recently discovered,&nbsp;exhibit&nbsp;many&nbsp;T-helper cell characteristics.&nbsp;ILCs, though few,&nbsp;produce cytokines, thereby&nbsp;significantly impacting&nbsp;tissue through local action in mucosal&nbsp;sites.&nbsp;They express the cell surface markers, CD90, which is unique to ILCs, and CD45, which all&nbsp;leukocyte&nbsp;types&nbsp;express.&nbsp;Colitis prevention&nbsp;in&nbsp;our&nbsp;model&nbsp;via ILC depletion&nbsp;indicates a role for ILCs in IBD.&nbsp;Therefore, we aimed&nbsp;to identify the ILCs’ localization in our murine model.&nbsp;We hypothesized that&nbsp;the ILCs will localize to inflamed areas of the intestinal lamina propria&nbsp;and&nbsp;into the&nbsp;intraepithelial spaces.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Mice expressing TNFAIP3, an inhibitor of NF-kB,&nbsp;were mated&nbsp;with adaptive immunity-lacking mice (RAG1<span data-fontsize="11">-/-</span>). RAG1<span data-fontsize="11">-/-</span>&nbsp;x Villin-TNFAIP3 (TRAG) mice&nbsp;had colitis that was 100% penetrant by age 6 weeks. Distal colons excised at&nbsp;age 4 weeks&nbsp;and 8 weeks&nbsp;were used for identifying&nbsp;CD45<span data-fontsize="11">+</span>&nbsp;and CD90<span data-fontsize="11">+&nbsp;</span>cells in&nbsp;both RAG and TRAG mice&nbsp;intestines&nbsp;via immunofluorescence.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>We observed differences in the distributions of CD90<span data-fontsize="11">+&nbsp;</span>and CD45<span data-fontsize="11">+&nbsp;</span>cells within&nbsp;TRAG and RAG mice intestines.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p>Differences&nbsp;exist&nbsp;in intestinal leukocyte distributions&nbsp;within our models.&nbsp;Altered ILC distribution&nbsp;might&nbsp;reflect&nbsp;an&nbsp;inflammatory state or contribute to IBD pathology.&nbsp;This work&nbsp;may&nbsp;further elucidate&nbsp;ILCs’&nbsp;role&nbsp;in IBD and as IBD&nbsp;treatment&nbsp;targets.</p> 2018-12-07T13:07:41-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22718 Birth Spacing and Family Planning: Implementation of enhanced education and training for Community Health Coaches 2019-01-08T13:22:01-05:00 Alexandra Jostes, BS BA imprs@iupui.edu Wilma Griffin, MS imprs@iupui.edu Paige Dechant, BS imprs@iupui.edu Carolina Otero, BA imprs@iupui.edu Kathleen Sobiech, PhD imprs@iupui.edu Denise V. Chico, BA imprs@iupui.edu Debra Litzelman, MD imprs@iupui.edu <p>&nbsp;</p> <p><strong>Background:</strong>&nbsp;Indiana is ranked 43/50 for infant mortality in America.&nbsp;WeCare&nbsp;employs lay Community Health Coaches (CHCs) to&nbsp;promote positive&nbsp;behavioral changes in pregnant, postpartum and women of child-bearing age&nbsp;living in low-income, high-risk communities&nbsp;in order to reduce the risk of infant mortality.&nbsp;Infant mortality&nbsp;can be reduced in communities where birth&nbsp;spacing&nbsp;and family planning education are available.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Project Methods:</strong><strong>&nbsp;</strong>The goal was to address the knowledge gaps in&nbsp;patient handouts and CHC training&nbsp;regarding birth spacing&nbsp;and family planning.&nbsp;Through extensive literature searches, case conferences with CHCs, and review of current training&nbsp;materials,&nbsp;five gaps in training were identified: (1)&nbsp;comprehensive knowledge of&nbsp;rapid repeat pregnancies (2)&nbsp;resources&nbsp;regarding&nbsp;contraceptive&nbsp;methods&nbsp;(3) contraceptive counseling in the&nbsp;antenatal and&nbsp;postpartum periods&nbsp;(4)&nbsp;joint&nbsp;decision-making&nbsp;models&nbsp;and (5) father involvement in family planning.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong>&nbsp;With comprehensive literature&nbsp;reviews&nbsp;and collaboration with fellow WeCare members, the gaps in&nbsp;training&nbsp;were&nbsp;appropriately filled. The WeCare training manual for CHCs is&nbsp;updated&nbsp;with&nbsp;information regarding birth spacing and family planning, as well as with counseling techniques for contraceptive method decision-making.&nbsp;A gap in existing literature regarding father involvement in family planning was identified.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact</strong><strong>:&nbsp;</strong>By&nbsp;enhancing CHC education on&nbsp;birth spacing,&nbsp;family planning,&nbsp;and&nbsp;counseling techniques,&nbsp;we may begin to close the knowledge&nbsp;gap&nbsp;for women in low-income, high-risk populations. This has the potential to&nbsp;reduce&nbsp;the rate of&nbsp;rapid repeat&nbsp;pregnancies&nbsp;and unintended pregnancies. We have also opened a&nbsp;new&nbsp;avenue&nbsp;of&nbsp;research&nbsp;about&nbsp;father involvement in family planning&nbsp;in the US.</p> 2018-12-07T13:08:29-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22719 Resiliency in Medical Students and Residents Participating in the Global Health AMPATH Kenya Elective 2019-01-08T13:22:01-05:00 Courtney L. Keilman imprs@iupui.edu Jenny Baenziger, MD imprs@iupui.edu <p>Burnout has become a prominent issue among healthcare providers. The demands of working long shifts, prolonged periods of stress and increased time spent charting all contribute to this phenomenon. Current research suggests that an intrinsic sense of resilience may be key in combating this epidemic. Just as our sense of empathy and compassion can be cultivated through experience, so too can our level of resilience. We propose that engaging in an international health project during medical professional education may promote a greater sense of resiliency. To analyze this, we will use the Connor-Davidson Resilience Scale© to survey 4<span data-fontsize="11">th</span>year medical students and residents at the Indiana University School of Medicine (IUSM) that have participated in the AMPATH rotation at&nbsp;Moi&nbsp;University in Kenya between June 2018 and May 2019. To determine the potential change in resilience we will ask our subjects to complete the survey prior to their trip, as well as 1-months and 1-year after their trip. This study may lead to the advocacy for such projects to be integrated into medical education curricula to combat the growing problem that is physician burnout.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:276}">&nbsp;</span></p> 2018-12-07T13:09:09-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22720 Impact of Hepatic Stellate Cells in Scaffold-Free 3D-Bioprinting of the Liver Model 2019-01-08T13:22:00-05:00 Cutter J. Koehler imprs@iupui.edu Wenjun Zhang imprs@iupui.edu Julia R. Walsh imprs@iupui.edu Raza A. Naqvi imprs@iupui.edu Erika Gramelspacher imprs@iupui.edu Lester J. Smith imprs@iupui.edu Ping Li imprs@iupui.edu Burcin Ekser imprs@iupui.edu <p><strong>Background and Hypothesis:</strong>&nbsp;Hepatic stellate cells (HSC), which compromise ~15% of liver cells, are vital to hepatocellular function.&nbsp;Scaffold-free 3D-bioprinting (SF3DBP) offers an&nbsp;avenue for the creation of realistic organ models without the use of biomaterials.&nbsp;Therefore, we hypothesized that co-culturing primary hepatocytes with HSC in SF3DBP liver model would uphold hepatocyte&nbsp;function&nbsp;over time, providing us a better 3D-liver model for research.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design:</strong>&nbsp;We used freshly&nbsp;thawed primary pig hepatocytes&nbsp;and immortalized pig HSC to generate spheroids with&nbsp;hepatocytes&nbsp;alone, HSC&nbsp;alone, or&nbsp;a&nbsp;combination of hepatocytes&nbsp;and HSC (2.5:1 ratio). Spheroids were formed using low adhesion plates, then characterized for distance from well center, diameter, roundness, and smoothness. A column of spheroids was printed using a&nbsp;Regenova&nbsp;3D-bioprinter. Remaining loose spheroids are incubated over two weeks for albumin secretion, mRNA transcription, and histological analysis<strong>.</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><strong>&nbsp;</strong>Co-cultures of hepatocytes and HSC (2.5:1 ratio) formed spheroids within 48 hours, as did HSC only spheroids (Figure 1). Spheroids composed of&nbsp;only&nbsp;hepatocytes failed to form&nbsp;round&nbsp;spheroids. The combination spheroids increased in roundness and decreased in diameter between characterizations over 6 days.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><strong>&nbsp;</strong>Spheroids proved too large to print at 48 hours but were successfully recognized and placed by the 3D-bioprinter. SF3DBP of combination spheroids would be viable by day 6. Optimization of spheroid composition using different cell ratios including HSC, hepatocytes, liver sinusoidal endothelial cells and fibroblasts, as well as optimization of spheroid incubation time will allow for production and printing of more advanced liver models.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> 2018-12-07T13:11:04-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22821 Are there sex-based differences in myocardial injury in Acute Heart Failure? 2019-01-08T13:22:00-05:00 Kaleb Kramer imprs@iupui.edu Benton Hunter, MD imprs@iupui.edu Phillip Levy, MD imprs@iupui.edu Sean Collins, MD imprs@iupui.edu Katie Lane, MS imprs@iupui.edu Xiaochun Li, PhD imprs@iupui.edu Peter S. Pang, MD imprs@iupui.edu <p><strong>Background and Hypothesis:&nbsp;</strong><span data-ccp-props="{}">&nbsp;</span></p> <p>Myocardial injury in acute heart failure (AHF) contributes to worse outcomes.&nbsp;&nbsp;Whether there are sex-based differences in organ injury in AHF is not well known. This&nbsp;study was designed to assess potential sex-based differences in myocardial injury, as defined by high-sensitivity troponin T (hsTnT) levels, in patients presenting in ED with AHF. We hypothesized that men with AHF have higher&nbsp;hsTnT&nbsp;levels.<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Project Methods:</strong><span data-ccp-props="{}">&nbsp;</span></p> <p>This is a preliminary analysis from the TACIT study, a large, prospective, multi-center, observational, biomarker cohort study.&nbsp; Adult patients diagnosed and treated for AHF, with a systolic blood pressure &gt;100mmHg, and enrolled within 3 hours of first AHF therapy were eligible. Febrile patients, short life-expectancy, ACS, AF with RVR &gt;130bpm, transplant, VAD, or ESRD were excluded.&nbsp;hsTnT&nbsp;were drawn at baseline and 3 hours later.&nbsp; Hemolyzed samples were disregarded as hemolysis falsely lowers&nbsp;hsTnT. A multivariable linear regression model was used to adjust for potential differences in baseline&nbsp;hsTnT&nbsp;using clinically meaningful covariates.&nbsp;&nbsp;<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Results:</strong><span data-ccp-props="{}">&nbsp;</span></p> <p>Of 527 enrolled, 499 comprised the final analysis set.&nbsp; Of these patients, 413 had a non-hemolyzed baseline&nbsp;hsTnT. Notably, more men than women were enrolled; men had higher mean baseline&nbsp;hsTnT&nbsp;values (48.3ng/mL,&nbsp;SD(74.5)) than women (28.3ng/mL SD(39.9)). After multivariable adjustment, baseline&nbsp;hsTnT&nbsp;differences by sex remained significant (p &lt;0.0001).<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><span data-ccp-props="{}">&nbsp;</span></p> <p>Men with AHF have higher baseline levels of myocardial injury than women. These differences may need to be taken into account for risk-stratification as well as management.<span data-ccp-props="{}">&nbsp;</span></p> 2018-12-07T13:11:42-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22721 Mapping Out Receptors: High Throughput Screening of Endothelial Monocyte Activating Polypeptide II (EMAPII) Using PRESTO-TANGO 2019-01-08T13:22:00-05:00 Nathan Lam imprs@iupui.edu Bernhard Maier imprs@iupui.edu Sarvesh Chelvanambi imprs@iupui.edu Takashi Hato imprs@iupui.edu Matthias Clauss imprs@iupui.edu <p><strong>Background</strong><strong>:</strong><strong>&nbsp;</strong>Secreted endothelial monocyte activating polypeptide II&nbsp;<strong>(</strong>EMAPII/AIMP1)&nbsp;is a pro-apoptotic, pro-inflammatory ligand implicated in diseases such as&nbsp;colorectal cancer,&nbsp;cardiovascular disease,&nbsp;and emphysema.&nbsp;Thus, EMAPII has been shown to induce apoptosis through CXCR3 receptor binding. However, not all&nbsp;EMAPII functions&nbsp;have been attributed to CXCR3.&nbsp;Discovery of new receptors interacting with EMAPII could lead to development of new therapies blocking cognate ligand-receptor binding.&nbsp;We hypothesize the existence of at least one unknown secondary receptor for EMAPII.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Methods:</strong><strong>&nbsp;</strong>The PRESTO-TANGO&nbsp;assay, a construct which converts G-protein coupled receptor (GPCR) ligand binding into luciferase activity&nbsp;measurable by&nbsp;luminometer, was validated using&nbsp;transfection with TANGO-modified&nbsp;CXCR3 and S1P1R as test receptors&nbsp;in HTLA cells.&nbsp;Protocols for cell transfection, adherence, and cultivation&nbsp;were optimized with IP10, EMAPII, and S1P as test ligands.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><strong>&nbsp;</strong>The assay was successfully validated using several&nbsp;GPCR activation&nbsp;readouts. Binding curves were generated for&nbsp;S1P/S1P1&nbsp;(EC<span data-fontsize="11">50</span>= 569nM), IP10/CXCR3 (EC<span data-fontsize="11">50</span>= 47.1&nbsp;nM), and&nbsp;EMAPII/CXCR3 (EC<span data-fontsize="11">50</span>= 628&nbsp;nM).&nbsp;Conditions for the PRESTO-TANGO assay were further refined for&nbsp;maximal signal-to-noise ratio and&nbsp;robust inter-assay reproducibility&nbsp;in preparation for high-throughput screening.&nbsp;We are currently&nbsp;testing&nbsp;314&nbsp;TANGO-modified&nbsp;GPCRs&nbsp;for EMAPII affinity.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion</strong><strong>:</strong><strong>&nbsp;</strong>We have validated the Tango assay for&nbsp;the known&nbsp;EMAPII-CXCR3 ligand-receptor system, a valuable tool for evaluation of anti-EMAPII therapeutics.<strong>&nbsp;</strong>Discovery of a novel EMAPII receptor would allow&nbsp;for the development of therapies&nbsp;including neutralizing&nbsp;antibodies&nbsp;(analogous to the PD1 receptor antibody&nbsp;Pembrolizumab&nbsp;for solid tumors)&nbsp;in diseases such as&nbsp;colorectal cancer,&nbsp;cardiovascular disease,&nbsp;and emphysema.</p> 2018-12-07T13:12:37-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22722 Store operated calcium entry in diabetic macrophages is reduced in fasting conditions 2019-01-08T13:22:00-05:00 Regina Lee imprs@iupui.edu Eleni Beli imprs@iupui.edu Chih-Chun Lee imprs@iupui.edu Tatsuyoshi Kono imprs@iupui.edu Carmella Evans-Molina imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><span data-ccp-props="{}">&nbsp;</span></p> <p>In diabetic mice, intermittent fasting (IF) prevents diabetic complications by temporarily reducing inflammation during the fasting period. As calcium homeostasis is tightly connected to the inflammatory response, we hypothesize that IF regulates macrophage response by altering store-operated calcium entry (SOCE). SOCE, mediated by the STIM and ORAI families, is the primary form of calcium entry into the cell.<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods:</strong><span data-ccp-props="{}">&nbsp;</span></p> <p>We assessed SOCE levels in control and diabetic (INS2<span data-fontsize="11">Akita</span>) mouse primary macrophages stimulated with a metabolic stimulus (MET: insulin, high glucose, palmitate) to mimic feeding and a starvation stimulus (STARVE: low glucose, low FBS, oleate) to mimic fasting. SOCE levels were measured by a&nbsp;Flexstation&nbsp;using Calcium-6 dye. We also assessed gene expression of SOCE components by RT-PCR and STIM1 and ORAI1 proteins by western blot.&nbsp;<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Results:</strong><span data-ccp-props="{}">&nbsp;</span></p> <p>A decrease in SOCE was observed with MET stimuli and an increase with STARVE&nbsp;stimuli&nbsp;in control macrophages. Interestingly, gene expression and protein levels of all major SOCE components, including STIM1 and ORAI1, were increased in the MET and decreased with STARVE. While diabetic macrophages had similar SOCE function than control under basal and MET conditions, they showed significantly downregulated SOCE under starvation conditions.<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><span data-ccp-props="{}">&nbsp;</span></p> <p>These data show that diabetic macrophages have altered SOCE function in response to fasting. This could have potential impact on how diabetic individuals respond to nutritional interventions such as IF that are recently proposed for prevention of diabetic complications.&nbsp;&nbsp;&nbsp;</p> 2018-12-07T13:13:14-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22723 Type 2 Diabetes Mouse Model: Insights into the Contribution of Metabolic Defects to Neurocognitive Decline 2019-01-08T13:21:59-05:00 Alexa Loncharich imprs@iupui.edu Austin Reilly imprs@iupui.edu Shijun Yan imprs@iupui.edu Hongxia Ren imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><strong>&nbsp;</strong>Metabolic diseases, including&nbsp;type 2 diabetes (T2D),&nbsp;have become&nbsp;increasingly prevalent and&nbsp;their&nbsp;associated medical costs have skyrocketed.&nbsp;Furthermore, recent epidemiological evidence&nbsp;suggests links between metabolic defects and neurodegenerative diseases, such as&nbsp;Alzheimer’s Disease (AD).&nbsp;The&nbsp;increasing&nbsp;coincidence&nbsp;of&nbsp;AD and&nbsp;T2D, and unmet treatment&nbsp;needs,&nbsp;necessitates&nbsp;research&nbsp;investigating&nbsp;potential shared mechanisms.&nbsp;To study glucose and lipid metabolism defects and neurocognitive deficits, we have generated non-obese insulin resistant mouse&nbsp;models,&nbsp;named&nbsp;GLUT4-mediated&nbsp;Insulin&nbsp;Receptor&nbsp;KnockOut&nbsp;(GIRKO).&nbsp;Insulin-responsive glucose transporter, Glut4,&nbsp;is expressed in&nbsp;muscle, fat, and&nbsp;a subset of neurons in the brain.&nbsp;Our previous publications show that GIRKO mice are highly insulin resistant&nbsp;and&nbsp;insulin sensitive GLUT4 neurons are critical mediators for&nbsp;glucose&nbsp;metabolism.&nbsp;We&nbsp;hypothesize&nbsp;that central insulin resistance in GIRKO mice&nbsp;instigates&nbsp;neurocognitive defects.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design:</strong><strong>&nbsp;</strong>We will measure the neurocognitive function of&nbsp;3- to 4-month old GIRKO&nbsp;mice&nbsp;using&nbsp;Morris water maze&nbsp;(MWM)&nbsp;test.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><strong>&nbsp;</strong>GIRKO mice&nbsp;exhibited&nbsp;increased escape latency.&nbsp;Additionally, they&nbsp;spent less time in the target&nbsp;quadrant&nbsp;in the probe trial,&nbsp;in which the platform is removed.&nbsp;GIRKO performed equally compared to control mice in raised platform tests, which demonstrates that motor competencies do not confound our findings.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559737&quot;:187,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><strong>&nbsp;</strong>GIRKO mice&nbsp;have&nbsp;learning and memory&nbsp;deficits, which&nbsp;illustrates&nbsp;a possible link between neurocognition and metabolism.&nbsp; Our results support the notion that insulin resistance precedes cognitive decline and necessitates early intervention therapy to treat insulin resistance and protect cognitive function.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> 2018-12-07T13:21:56-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22724 Genetic Defects in SHROOM3 Lead to Congenital Heart Defects 2019-01-08T13:21:59-05:00 Samuel Lorentz imprs@iupui.edu Matthew D. Durbin, MD, MS imprs@iupui.edu Stephanie Ware, MD, PhD imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><strong>&nbsp;</strong>Congenital heart&nbsp;disease(CHD)&nbsp;is the most common birth defect,&nbsp;but most&nbsp;genetic contributors&nbsp;remain&nbsp;unknown.&nbsp;We recently identified CHD patients with variants in a gene called&nbsp;<em>SHROOM3</em><em>.&nbsp;</em>The&nbsp;SHROOM3 protein&nbsp;impacts the&nbsp;actin cytoskeleton&nbsp;by&nbsp;binding&nbsp;ActinF&nbsp;and Rho-kinase,&nbsp;causing actomyosin constriction.&nbsp;SHROOM3<em>&nbsp;</em>also&nbsp;binds&nbsp;Dishevelled2(Dvl2), a component of&nbsp;Wnt/Planar cell&nbsp;polarity(PCP)&nbsp;signaling pathway, suggesting a connection between PCP signaling and actin-myosin contraction.&nbsp;We&nbsp;hypothesize&nbsp;<em>SHROOM3</em>&nbsp;disruption&nbsp;alters PCP signaling and actin cytoskeleton during cardiac development, and&nbsp;is a novel contributor to&nbsp;CHD.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Project Methods:</strong><strong>&nbsp;</strong>We&nbsp;analyzed the cardiac phenotype of&nbsp;<em>Shroom3</em>&nbsp;gene trap&nbsp;knockout mice at embryonic day&nbsp;14.5.&nbsp;We characterized the expression of&nbsp;<em>S</em><em>hroom</em><em>3</em>&nbsp;during cardiac development using LacZ&nbsp;staining&nbsp;at important stages of cardiac development.&nbsp;Using&nbsp;IHC, we measured actomyosin disruption&nbsp;in&nbsp;<em>Shroom3</em>&nbsp;knockout embryos.&nbsp;We&nbsp;preformed&nbsp;in silico analysis on&nbsp;previously identified&nbsp;<em>SHROOM3</em>&nbsp;variants from&nbsp;patients with CHD.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><strong>&nbsp;</strong><em>Shroom</em><em>3</em>&nbsp;null mice&nbsp;had&nbsp;Ventricular Septal Defects&nbsp;(0.73, p=0.0006),&nbsp;Double Outlet Right&nbsp;Ventricle (0.33, p=0.04), Left Ventricular Noncompaction, and&nbsp;other&nbsp;CHD.&nbsp;<em>Shroom3&nbsp;</em>mutant mice left ventricular wall thickness was&nbsp;36%&nbsp;thinner&nbsp;compared to&nbsp;wild type&nbsp;mice&nbsp;(99.0±8.6µm, 63.0±8.4µm,&nbsp;p=0.005).&nbsp;LacZ shows the expression of&nbsp;<em>S</em><em>hroom</em><em>3</em>&nbsp;through important stages of&nbsp;cardiac&nbsp;development, and IHC shows actomyosin disruption.&nbsp;In silico analysis&nbsp;demonstrates&nbsp;CHD patients have&nbsp;<em>SHROOM3</em>&nbsp;variants&nbsp;in highly&nbsp;conserved&nbsp;nucleic acid and protein sequences, and significant protein structural changes.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:1,&quot;335559739&quot;:160,&quot;335559740&quot;:260}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong>&nbsp;<em>Shroom3</em>&nbsp;null&nbsp;mice have cardiac defects&nbsp;resembling&nbsp;a&nbsp;Wnt/PCP disruption&nbsp;phenotype. Similarly,&nbsp;patients with CHD&nbsp;have&nbsp;likely&nbsp;pathogenic variants in&nbsp;<em>SHROOM3</em>.&nbsp;These&nbsp;data&nbsp;support a role for&nbsp;<em>SHROOM3</em>&nbsp;in CHD pathogenesis&nbsp;and begin to elucidate mechanisms.&nbsp;Identifying&nbsp;<em>SHROOM3</em>’s role&nbsp;in CHD is&nbsp;critical&nbsp;to&nbsp;understanding&nbsp;cardiac development as well as the diagnosis, management and&nbsp;treatment of CHD.</p> 2018-12-07T13:22:26-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22725 Cardiovascular Effects of Sodium Glucose Cotransporter-2 (SGLT-2) Inhibition in the Setting of Ischemia/Reperfusion Injury 2019-01-08T13:21:59-05:00 Sam Luebbe imprs@iupui.edu Hana E. Baker imprs@iupui.edu Kieren J. Mather imprs@iupui.edu Adam G. Goodwill imprs@iupui.edu Blake R. Simon imprs@iupui.edu Conner C. Earl imprs@iupui.edu Johnathan D. Tune imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><strong>&nbsp;</strong>Recent evidence indicates that sodium glucose cotransporter-2 inhibitors (SGLT2i) significantly reduce the incidence of major adverse cardiovascular events in high risk patients. However, the specific effects of SGLT2i on the cardiovascular system remain poorly defined. This study&nbsp;was&nbsp;designed to test the hypothesis that SGLT2i improves cardiac function and mitigates myocardial infarct size following regional myocardial ischemia and reperfusion injury.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experi</strong><strong>mental Design</strong><strong>:</strong><strong>&nbsp;</strong>Lean domestic swine received placebo&nbsp;(n=6)&nbsp;or canagliflozin (n=6;&nbsp;300 mg PO) 24 hours prior to and the morning of an experiment.&nbsp;Hemodynamics,&nbsp;left ventricular pressure and volume&nbsp;were&nbsp;measured in open chest,&nbsp;swine at baseline, during a 60&nbsp;min&nbsp;coronary&nbsp;occlusion,&nbsp;and during a&nbsp;2-hour&nbsp;reperfusion period.&nbsp;The degree of myocardial infarction was assessed by staining&nbsp;with 1% tetrazolium.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><strong>&nbsp;</strong>At the onset of ischemia, SGLT2i produced a significant parallel increase in both left ventricular end diastolic (85 ± 9 mL to 129 ± 10 mL;&nbsp;<em>P</em>&nbsp;&lt; 0.05) and end systolic volumes (29 ± 8 mL to 78 ± 9 mL;&nbsp;<em>P</em>&nbsp;&lt; 0.01). This increase in ventricular filling was associated with significant increases in stroke volume (<em>P&nbsp;</em>&lt; 0.05) and stroke work (<em>P&nbsp;</em>&lt; 0.05) relative to untreated controls swine during ischemia.&nbsp; SGLT2i&nbsp;decreased infarct size&nbsp;from&nbsp;9.4&nbsp;[Symbol]&nbsp;2.1%&nbsp;in control&nbsp;swine to&nbsp;3.1&nbsp;[Symbol]&nbsp;0.98%&nbsp;in SGLT2i treated swine.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion</strong><strong>:</strong><strong>&nbsp;</strong>SGLT2 inhibitors significantly&nbsp;improve cardiac contractile function and&nbsp;mitigate myocardial infarct size following regional myocardial ischemia and reperfusion injury&nbsp;in domestic swine.</p> 2018-12-07T13:23:07-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22728 Fidelity of Peer Supported Self-Management of Chronic Pain (Evaluation of a Peer Coach-Led Intervention to Improve Pain Symptoms—ECLIPSE) 2019-01-08T13:21:58-05:00 Joyce S. Mannon, B.S. imprs@iupui.edu Marianne S. Matthias, Ph.D. imprs@iupui.edu <p><strong>Background:</strong><strong>&nbsp;</strong>ECLIPSE&nbsp;(Evaluation of a Peer Coach-Led Intervention to Improve Pain Symptoms) is a randomized controlled trial testing&nbsp;peer-supported&nbsp;chronic&nbsp;pain self-management.&nbsp;Veterans are paired with a peer coach (also&nbsp;with&nbsp;chronic pain) for 6 months. Peer coaches&nbsp;(PCs)&nbsp;and veterans meet or talk by phone&nbsp;2x/month about pain self-management&nbsp;strategies, and veterans receive motivation and encouragement from their PC.&nbsp;To determine if the intervention&nbsp;was&nbsp;delivered as intended, fidelity was assessed at the end of the intervention period.&nbsp;Fidelity&nbsp;assessment&nbsp;is vital to&nbsp;help understand reasons for&nbsp;an intervention’s success or failure.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Methods:</strong>&nbsp;Intervention veterans were asked about the intervention’s delivery during their 6-month assessment, after&nbsp;intervention&nbsp;completion. Presence or absence of four “essential elements” of the intervention were evaluated, as well as meeting frequency.&nbsp;&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><strong>&nbsp;</strong>Scoring of&nbsp;veteran assessments&nbsp;revealed&nbsp;74%&nbsp;of&nbsp;PC’s discussed self-management strategies and 69% of veterans felt motivated by their&nbsp;PC.&nbsp;Only 52% discussed&nbsp;how to adjust strategies and 34% discussed goal-setting.&nbsp;PC-veteran&nbsp;meeting&nbsp;frequency varied:&nbsp;16% met weekly, 21% met twice a month, 16% met once a month, and 46%&nbsp;met less than once a month. 47%&nbsp;of PC’s&nbsp;had greater than 75% fidelity&nbsp;(i.e., the presence of at least 3 of 4 elements described above).&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><strong>&nbsp;</strong>About half of PC’s&nbsp;delivered the&nbsp;intervention with&nbsp;at least 75%&nbsp;fidelity.&nbsp;Fidelity was greater for&nbsp;discussing self-management strategies and motivating&nbsp;veterans.&nbsp;Results suggest that peer-supported self-management&nbsp;can be delivered with fidelity but PCs may need additional training to do so consistently.</p> 2018-12-07T13:23:40-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22729 MELodica Orchestra for DYspnea (MELODY): A Randomized Safety, Feasibility, and Efficacy Pilot 2019-01-08T13:21:58-05:00 Mackenzie McGrath imprs@iupui.edu Debra S. Burns imprs@iupui.edu Shannon Crow imprs@iupui.edu Aimee Lillie imprs@iupui.edu Laura J. Myers imprs@iupui.edu Jennifer Myers imprs@iupui.edu Anthony J. Perkins imprs@iupui.edu Nicholas Rattray imprs@iupui.edu Joseph Smith imprs@iupui.edu Sally Wasmuth imprs@iupui.edu Dawn M. Bravata imprs@iupui.edu <p><strong>Background</strong><span data-ccp-props="{&quot;335559739&quot;:160}">&nbsp;</span></p> <p>Chronic obstructive pulmonary disease (COPD)&nbsp;is&nbsp;highly&nbsp;prevalent&nbsp;among&nbsp;Veterans.&nbsp;Patients with COPD commonly experience dyspnea, which&nbsp;can be debilitating&nbsp;and may limit&nbsp;daily activities&nbsp;leading to a reduced quality of life.&nbsp;Pulmonary rehabilitation often&nbsp;includes teaching&nbsp;pursed lip breathing as a method to reduce dyspnea. However,&nbsp;patients with COPD, including Veterans,&nbsp;have limited access to&nbsp;pulmonary rehabilitation&nbsp;due to transportation constraints&nbsp;and&nbsp;lack of referrals by&nbsp;physicians.<span data-ccp-props="{&quot;335559739&quot;:160}">&nbsp;</span></p> <p><strong>Methods</strong><span data-ccp-props="{&quot;335559739&quot;:160}">&nbsp;</span></p> <p>MELodica&nbsp;Orchestra for&nbsp;DYspnea&nbsp;(MELODY) is a&nbsp;randomized&nbsp;controlled&nbsp;clinical trial&nbsp;designed&nbsp;to assess the safety,&nbsp;feasibility, and efficacy&nbsp;of a music-based approach&nbsp;to&nbsp;teach&nbsp;pursed lip breathing to&nbsp;Veterans&nbsp;with COPD&nbsp;experiencing&nbsp;dyspnea.&nbsp;Patients will be randomized in a 1:1:1 ratio to the intervention group,&nbsp;education only control group, and usual care control group&nbsp;using block randomization. Patients in the intervention group&nbsp;will meet twice weekly over twelve weeks for instruction on how to&nbsp;play&nbsp;the melodica&nbsp;and&nbsp;to&nbsp;participate in&nbsp;group music-making. The program also includes education about COPD, pursed lip breathing,&nbsp;tobacco cessation, and other relevant topics.&nbsp;Each&nbsp;participant&nbsp;will receive quantitative assessments (e.g.,&nbsp;exercise endurance&nbsp;and dyspnea&nbsp;scales)&nbsp;and&nbsp;participate&nbsp;in qualitative interviews.&nbsp;<span data-ccp-props="{&quot;335559739&quot;:160}">&nbsp;</span></p> <p><strong>Anticipated Results</strong><span data-ccp-props="{&quot;335559739&quot;:160}">&nbsp;</span></p> <p>We expect the&nbsp;intervention&nbsp;to be safe and&nbsp;feasible. We&nbsp;hypothesize that&nbsp;patients&nbsp;in the intervention group&nbsp;will achieve the greatest reduction in dyspnea&nbsp;compared with patients in either control group.<span data-ccp-props="{&quot;335559739&quot;:160}">&nbsp;</span></p> <p><strong>Potential Impact</strong><span data-ccp-props="{&quot;335559739&quot;:160}">&nbsp;</span></p> <p>If&nbsp;pilot data demonstrates&nbsp;efficacy,&nbsp;then a&nbsp;multiple-site&nbsp;randomized control trial&nbsp;will&nbsp;be conducted with&nbsp;intent to introduce&nbsp;the program&nbsp;into&nbsp;routine&nbsp;clinical practice.&nbsp;</p> 2018-12-07T13:24:39-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22730 Evaluation of a Critical Sized Bone Defect in a Porcine Tibial Model 2019-01-08T13:21:58-05:00 Anthony J. Milto imprs@iupui.edu Alexander W. Peters imprs@iupui.edu Aamir Tucker imprs@iupui.edu Alex Brinker imprs@iupui.edu Michael Savaglio imprs@iupui.edu Gremah Adam imprs@iupui.edu Venkateswaran Ganesh imprs@iupui.edu Zachary Gunderson imprs@iupui.edu Paul Childress imprs@iupui.edu Roman M. Natoli imprs@iupui.edu Todd O. McKinley imprs@iupui.edu Melissa A. Kacena imprs@iupui.edu <p><strong>Background/Hypothesis</strong>:</p> <p>Few large animal bone injury models exist. We present a porcine tibial model of metacritical and critical sized bone defects for the simulation of traumatic bone injuries.</p> <p><strong>Project Methods:</strong></p> <p>16 pigs were used in this study. The pigs were divided into 3 groups (n=4-8/group). In 12 pigs, a 25 mm osteotomy was created in the tibia and the space was filled with a 25 mm scaffold. 8 of the 25 mm scaffolds were secured with an intramedullary (IM) nail and 4 of the scaffolds were secured with plates. In 4 pigs a 40 mm osteotomy was created, filled with a 40 mm scaffold, and secured with plates. Fracture healing was assessed 3 months post-operatively using the Radiographic Union Score for Tibial Fractures (RUST) criteria.</p> <p><strong>Results:</strong></p> <p>For the 25 mm IM group, none of the 8 pigs achieved cortical bone union at 3 months post-op. In contrast, cortical union was observed in all of the 25 mm defects secured with plates. None of the 40 mm defects secured with plates achieved cortical union.</p> <p><strong>Conclusion/Potential Impact:</strong></p> <p>The failure of the 25 mm defect secured with an IM nail and the 40 mm defect secured with plates demonstrates that these are critical sized defect models. However, because the 25 mm defect secured with bridge plates did heal, we have termed this a metacritical sized defect. Identification of a defect size that can heal or not heal based on the fixation technique is a powerful translational model for testing therapies.</p> 2018-12-07T13:25:06-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22731 Understanding the Algebraic and Logical Structure of Speech Perception 2019-01-08T13:21:58-05:00 Kalina A. Misiolek imprs@iupui.edu Robert M. Worth imprs@iupui.edu Leonid L. Rubchinsky imprs@iupui.edu <p><strong>Background:</strong><strong>&nbsp;</strong>Although subject to much variation, the anatomy of language comprehension has become&nbsp;increasingly&nbsp;clear with the advent of fMRI;&nbsp;however,&nbsp;the&nbsp;steps&nbsp;of&nbsp;speech comprehension&nbsp;remain&nbsp;elusive.&nbsp;There are two&nbsp;main&nbsp;theories of language processing – hierarchical and sequential&nbsp;(or probabilistic).&nbsp;According to the hierarchical theory,&nbsp;sentences&nbsp;are&nbsp;broken down (e.g. sentence to words to syllables to phonemes) and then reconstructed while syntactic and semantic meanings&nbsp;are&nbsp;attached.&nbsp;Sequential theory suggests&nbsp;the use of&nbsp;“word-level statistics” and n-gram-type models to predict sequences of word meanings.<span data-fontsize="11">1</span>&nbsp;Although evidence suggests&nbsp;both models play&nbsp;some&nbsp;role, as a starting point, many comprehension&nbsp;models&nbsp;focus on hierarchical theory, and many of those in turn rely on neural networks. However, in various ways, these models fall short of&nbsp;explaining how the brain can biologically carry out all the steps.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Methods:</strong><strong>&nbsp;</strong>We attempt to&nbsp;create a&nbsp;hierarchical model of speech comprehension using linear logic (or a related logic) or Category Theory, with the&nbsp;hope&nbsp;that&nbsp;such an approach&nbsp;may be able to explain the process more naturally. We&nbsp;focus&nbsp;on the second half of comprehension (i.e. the reconstruction) to make use of existing neuronal logic gate models.<span data-fontsize="11">2</span>&nbsp;The goal is to construct a linear logic&nbsp;model&nbsp;or to create categories and associated&nbsp;functors&nbsp;that could explain hierarchical linguistic processing and&nbsp;many&nbsp;neurolinguistic study results.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Potential Impact:</strong><strong>&nbsp;</strong>Although this model would only account for hierarchical linguistic processing, it would be a huge step forward in understanding how our brain processes speech – and possibly other inputs&nbsp;– at the level of neuron bundles.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>References:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <ol> <li data-leveltext="%1." data-font="Arial" data-listid="1" aria-setsize="-1" data-aria-posinset="1" data-aria-level="1">Frank, S. L., Christiansen, M. H. (2018). Hierarchical and sequential processing of language.&nbsp;<em>Language, Cognition and Neuroscience,</em>&nbsp;1-6. doi:10.1080/23273798.2018.1424347<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></li> </ol> <ol> <li data-leveltext="%1." data-font="Arial" data-listid="1" aria-setsize="-1" data-aria-posinset="2" data-aria-level="1">Goldental, A.,&nbsp;Guberman, S.,&nbsp;Vardi, R., &amp; Kanter, I. (2014). A computational paradigm for dynamic logic-gates in neuronal activity.&nbsp;<em>Frontiers in Computational Neuroscience,</em>&nbsp;<em>8</em>. doi:10.3389/fncom.2014.00052<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></li> </ol> 2018-12-07T13:28:56-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22732 Effect of Signal-Dependent Noise on Phase Synchrony Pattern 2019-01-08T13:21:57-05:00 Kalina A. Misiolek imprs@iupui.edu Leonid L. Rubchinsky imprs@iupui.edu Robert M. Worth imprs@iupui.edu <p><strong>Background:&nbsp;</strong>Intermittent phase synchrony is a phenomenon&nbsp;that occurs at subthreshold levels of oscillator coupling, where two oscillators appear to be synchronized at some times and desynchronized at others. Here, periods of “synchrony” are defined by a certain amount of statistically significant correlation between the time series of the oscillators.<span data-fontsize="11">1</span>&nbsp;While general synchrony is observable in any number of settings&nbsp;(e.g. coupled pendula), intermittent synchrony has been detected in EEG readings from specific pairs of electrodes from patients with schizophrenia and Parkinson’s Disease.<span data-fontsize="11">1</span>&nbsp;However, the extent to which EEG noise impacts synchrony pattern&nbsp;within the&nbsp;Rubchinsky&nbsp;et. al. model&nbsp;has not yet been studied.<span data-fontsize="11">1</span><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Methods:&nbsp;</strong>Using non-experimental data in MATLAB, we propose to run a series of trials to study the effect of signal-dependent multiplicative noise on the patterns of phase synchrony between oscillators. In the first condition, we simulate two completely synchronized signals, add signal-dependent noise to one, and observe the resulting changes to the synchronization pattern. In the second condition, we&nbsp;begin with&nbsp;two completely&nbsp;desynchronized&nbsp;signals.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Potential Impact:&nbsp;</strong>In studies of intermittent phase synchrony, it has been suggested that this pattern is the result of neuronal circuits which, as the EEG&nbsp;signals&nbsp;synchronize, fire more strongly and as a result become less responsive to outside input. This interpretation has the power to&nbsp;explain some of the symptoms experienced by patients.&nbsp;Thus, the specific pattern of synchronized and de-synchronized episodes is potentially highly significant.&nbsp;Our&nbsp;study is a necessary first step to understanding if the existing model and interpretations are accurate.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>References:</strong></p> <ol> <li data-leveltext="%1." data-font="Arial" data-listid="1" aria-setsize="-1" data-aria-posinset="1" data-aria-level="1">Rubchinsky, L. L.,&nbsp;Ahn, S., &amp; Park, C. (2014). Dynamics of desynchronized episodes in intermittent synchronization.&nbsp;<em>Frontiers in Physics,</em>&nbsp;<em>2</em>. doi:10.3389/fphy.2014.00038<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></li> </ol> 2018-12-07T13:29:36-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22733 REDUCED INFECTION RATE AFTER ASEPTIC REVISION TOTAL HIP ARTHROPLASTY WITH EXTENDED ORAL ANTIBIOTIC PROTOCOL 2019-01-08T13:21:57-05:00 Amer Mohiuddin, BS imprs@iupui.edu Justin Rice, BA imprs@iupui.edu Mary Ziemba-Davis, BA imprs@iupui.edu R. Michael Meneghini, MD imprs@iupui.edu <p><strong>Background and Hypothesis</strong><strong>:</strong>&nbsp;Periprosthetic joint infection (PJI is a leading cause of failure after&nbsp;aseptic&nbsp;revision&nbsp;total hip arthroplasty (RTHA).&nbsp;While well documented in the primary setting, perioperative&nbsp;antibiotic duration is not&nbsp;well described in RTHA where&nbsp;the&nbsp;risk of PJI&nbsp;was recently reported&nbsp;to be 8%&nbsp;one-year post-revision.&nbsp;The study purpose was to evaluate&nbsp;whether&nbsp;extended&nbsp;oral&nbsp;antibiotic&nbsp;prophylactic protocol&nbsp;minimizes PJI in aseptic RTHA patients compared to the published literature.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Project&nbsp;</strong><strong>Methods:</strong>&nbsp;169&nbsp;consecutive&nbsp;aseptic&nbsp;RTHAs&nbsp;performed&nbsp;with modern perioperative&nbsp;and infection-prevention&nbsp;protocols&nbsp;by a single surgeon at a&nbsp;single&nbsp;center&nbsp;were&nbsp;retrospectively reviewed.&nbsp;80% of&nbsp;patients&nbsp;were&nbsp;discharged on 7-day oral antibiotic prophylaxis&nbsp;while intra-operative cultures were incubating.&nbsp;Infections and reoperations&nbsp;were&nbsp;documented.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong>&nbsp;Average&nbsp;age&nbsp;and&nbsp;BMI&nbsp;were 63 years and&nbsp;30&nbsp;kg/m<span data-fontsize="11">2</span>.&nbsp;&nbsp;67% percent&nbsp;of patients were ASA-III/IV, signifying the severity of comorbidities in this revision cohort.&nbsp;There we no cases of PJI in the 90-day postoperative period.&nbsp;Ninety-eight percent&nbsp;of cases were infection free&nbsp;at mean follow-up of&nbsp;45&nbsp;months.&nbsp;Three&nbsp;(1.8%)&nbsp;cases&nbsp;underwent reoperation for deep infection&nbsp;at 110,&nbsp;161 and 581&nbsp;days.&nbsp;&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion</strong><strong>&nbsp;and Potential Impact</strong><strong>:</strong>&nbsp;Our observed infection rate of 0.0% is lower than&nbsp;published infection rates following RTHA&nbsp;and a 1.5%&nbsp;infection rate in primary THA in patients with no identifiable risk factors for PJI.&nbsp;&nbsp;Based on this&nbsp;clinically meaningful&nbsp;decrease in PJI&nbsp;in this&nbsp;challenging cohort, we encourage further study&nbsp;regarding&nbsp;extended antibiotic protocol&nbsp;weighed appropriately against&nbsp;potential&nbsp;consequences.&nbsp;&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> 2018-12-07T13:30:15-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22734 SILDENAFIL IS NOT PROTECTIVE TO THE BOWEL FOLLOWING INTESTINAL ISCHEMIA AND REPERFUSION INJURY 2019-01-08T13:21:57-05:00 Hannah M. Moore, BS imprs@iupui.edu Natalie A. Drucker, M.D. imprs@iupui.edu Troy A. Markel, M.D imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Acute Mesenteric Ischemia (AMI) occurs when blood supply to the intestine is decreased. This can lead to intestinal ischemia, cellular damage, necrosis, and if corrected, subsequent reperfusion injury. There are currently no medical treatments to help reverse ischemia and reperfusion injury (I/R) and, therefore novel treatments are necessary. Sildenafil, a compound that increases endogenous nitric oxide (NO) by blocking the phosphodiesterase-5 induced breakdown of cGMP, may function as a potent mesenteric vasodilator.&nbsp; We therefore hypothesized that sildenafil would improve mesenteric perfusion during a mouse model of intestinal I/R. <span data-ccp-props="{&quot;134233117&quot;:true,&quot;134233118&quot;:true,&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Adult male C57Bl6J mice were anesthetized with isoflurane and a midline laparotomy performed. The base of the superior mesenteric artery was occluded with a non-crushing vascular clamp for 60 minutes. At the end of ischemia, sildenafil (1mg/kg, 10mg/kg, or 100mg/kg) or a PBS vehicle control were administered via intraperitoneal injection. Animals were then allowed to recover.&nbsp; Twenty-four hours after ischemia, animals underwent assessment of mesenteric perfusion by Laser-Doppler imaging. Animals were then euthanized.&nbsp; Perfusion was expressed as a percentage of baseline, depicted as mean +/- SEM, and analyzed by ANOVA.&nbsp; P&lt;0.05 was significant.<span data-ccp-props="{&quot;134233117&quot;:true,&quot;134233118&quot;:true,&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Results:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>There were no significant differences in mesenteric perfusion between the vehicle group or any of the therapeutic groups.&nbsp; (PBS: 53.03±11.35%; Sildenafil-low: 59.59±7.55%; Sildenafil-medium: 70.51±8.49; Sildenafil-high: 66.4±10.2, p=0.61).&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p>Sildenafil does not appear to be an effective treatment for improving mesenteric perfusion following intestinal ischemia. Further studies are required to determine the reasons for the ineffectiveness of sildenafil.&nbsp; One possible explanation for these observations could be a lack of PGE5 in the intestinal vascular endothelium.&nbsp;&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> 2018-12-07T13:30:40-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22822 Impact of ED Scribes in a Residency Program 2019-01-08T13:21:57-05:00 Mumtaz Munshi, BS imprs@iupui.edu Daniel Corson-Knowles, MD imprs@iupui.edu Nash Whitaker imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><strong>&nbsp;</strong>In the&nbsp;electronic medical record&nbsp;era, clerical&nbsp;documentation&nbsp;has become a significant source of burden in the&nbsp;emergency department (ED). Medical scribes&nbsp;have been advocated as a method to reduce clerical documentation burden while improving physician productivity and satisfaction. The impact of scribes in a non-academic ED setting has been found&nbsp;to be&nbsp;beneficial, and a small survey suggested resident&nbsp;physicians&nbsp;found scribes to&nbsp;be&nbsp;a valuable fatigue-mitigation strategy. The goal of this study was to assess the impact of ED scribes on residents, including time burden of documentation, signals of emotional impact that contribute to burnout, and learning/teaching opportunities.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods:</strong><strong>&nbsp;</strong>This&nbsp;observational&nbsp;time motion analysis&nbsp;assesses&nbsp;scribe impact on&nbsp;emergency medicine residents.&nbsp;Observations were pseudo-randomized in a 1:1 fashion to shifts without or with scribes. Trained observers&nbsp;tracked the activity of upper level residents in the high acuity&nbsp;section&nbsp;of&nbsp;a busy urban&nbsp;county&nbsp;ED for 4 hours of each shift. At the end of&nbsp;each&nbsp;shift, residents self-reported post-shift documentation time and completed a survey assessing&nbsp;residents’ perception of their shift and the impact of scribes.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><strong>&nbsp;</strong>Residents reported that scribes improved their overall experience during their shift. They also reported that scribes reduced documentation time&nbsp;(0:11:33&nbsp;[Symbol]0:04:24&nbsp;v.&nbsp;0:08:56&nbsp;[Symbol]0:05:36)&nbsp;and allowed them to better connect with and care more for their patients&nbsp;(9.6&nbsp;[Symbol]0.8&nbsp;v.&nbsp;8.7[Symbol]1.3).&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><strong>&nbsp;</strong>Scribes improved&nbsp;emergency medicine&nbsp;residents’ perceptions&nbsp;of their educational experience and reduced symptoms of burnout&nbsp;during shifts.&nbsp;</p> 2018-12-07T13:31:20-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22735 Disease Severity in Non-alcoholic Fatty Liver Disease (NAFLD) Patients with No Prior Diagnosis of Cirrhosis – A Unique Insight Using Vibration-Controlled Transient Elastography (VCTE) 2019-01-08T13:21:56-05:00 David Muschi imprs@iupui.edu Dr. Raj Vuppalanchi imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>The severity of fibrosis is a strong prognostic indicator in patients with non-alcoholic fatty liver disease (NAFLD). However, routine evaluation with a liver biopsy in patients with NAFLD is not feasible and as such, the assessment of disease severity is often limited in small sample sizes. Vibration-controlled transient elastography (VCTE) is a non-invasive tool that can simultaneously assess for both liver fibrosis and steatosis by estimating liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) respectively.&nbsp;&nbsp;The aim of the current study is to estimate the prevalence of (1) abnormal LSM indicative of any fibrosis based on LSM ≥ 6.5 kPa, (2)&nbsp;compensated Advanced Chronic Liver Disease&nbsp;(cACLD)&nbsp;– suggestive(10-15kPa)&nbsp;and highly&nbsp;suggestive&nbsp;(&gt;15 kPa), and (3) severe steatosis&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Patients seen at digestive and liver&nbsp;disorders clinic at Indiana University Hospital that underwent VCTE between 8/2013-4/2018 were identified from the Fibrocan502 Touch data table. The ICD10 codes used as the indication for performing the VCTE were extracted and confirmed with the&nbsp;review of electronic health records.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>1240 patients&nbsp;met the criteria.&nbsp;&nbsp;The prevalence of abnormal LSM in the study cohort was 66% with 38.5 % having LSM suggestive of&nbsp;cACLD&nbsp;and 22% having LSM highly suggestive of&nbsp;cACLD. The prevalence of severe steatosis was 77%. The proportion of NAFLD patients with&nbsp;cACLD&nbsp;(suggestive and highly suggestive) during the study period was not significantly different (Figure1).&nbsp;&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong>&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p>There are many NAFLD patients with liver stiffness indicative of abnormal LSM and 22% have LSM that is highly suggestive of&nbsp;cACLD. The proportion of patients with&nbsp;cACLD&nbsp;is steady over the study duration.&nbsp;</p> 2018-12-07T13:31:47-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22736 Association of AHI and Other Patient Factors with Calvarial Thickness 2019-01-08T13:21:56-05:00 Amit Nag, BS imprs@iupui.edu Cyrus Rabbani, MD imprs@iupui.edu Mohamad Z. Saltagi, MD imprs@iupui.edu Elizabeth Schueth, BS imprs@iupui.edu Rick F. Nelson, MD, PhD imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><strong>&nbsp;</strong>Temporal spontaneous cerebrospinal fluid (sCSF) leaks occur when spinal fluid leaks&nbsp;through defects in the&nbsp;skull base bone.&nbsp;Patients with&nbsp;sCSF&nbsp;leaks have approximately 22% thinner skulls but no change in extracranial bone thickness, suggesting&nbsp;an intracranial process causes skull thinning and the development of&nbsp;sCSF&nbsp;leaks.&nbsp; Approximately 83% of&nbsp;sCSF&nbsp;leak patients have obstructive sleep apnea (OSA) as measured by the apnea-hyponea&nbsp;index (AHI) and OSA is associated with spikes in intracranial pressure.&nbsp;We hypothesize that&nbsp;AHI is associated with isolated skull thinning in the general population.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design:</strong>&nbsp;&nbsp;High resolution head CT images from patients with diagnostic sleep studies at IU health from 2010 to 2017 were analyzed (IRB approved) using 3D slicer to measure skull thickness of the squamous temporal bone. Age, body mass index (BMI), race and diabetes recorded.&nbsp;Mixed model&nbsp;analysis&nbsp;was&nbsp;used to determine&nbsp;the effect of a number of&nbsp;factors&nbsp;on skull thickness.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><strong>&nbsp;</strong>344 CT&nbsp;scans&nbsp;were analyzed.&nbsp;Increased AHI was significantly associated with thinning of the calvarium [2.68 mm - 0.003x, (x = AHI&nbsp;point)&nbsp; P&lt;0.02], while thickening of the calvarium was associated with age [CI&nbsp;= 0.005 to 0.011 per&nbsp;year, P&lt;0.001] and&nbsp;BMI [CI = 0.003 to 0.015 per mg/kg<span data-fontsize="11">2</span>, P&lt;0.003].&nbsp;Female gender (P=0.016) and diabetes (P=0.005) were linked to thickening of the calvarium. Hypertension&nbsp;had no effect on&nbsp;calvarial&nbsp;and zygoma&nbsp;thickness (P=0.244&nbsp;and 0.575, respectively).&nbsp;The extracranial zygoma&nbsp;thickness&nbsp;was not associated with AHI (P=0.54)&nbsp;or BMI (P=0.811)&nbsp;but the zygoma thinned significantly with age [CI = -0.01 to&nbsp;-&nbsp;0.002,&nbsp;P&lt;0.002] and female gender (P&lt;0.001).<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><strong>&nbsp;</strong><strong>&nbsp;</strong>OSA is associated with skull thinning and may play a pathologic role in the development of&nbsp;sCSF&nbsp;leaks&nbsp;over time.<strong>&nbsp;</strong></p> 2018-12-07T13:36:17-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22737 Role of CCL21 on the Transcriptional Regulation of MHC II in Malignant Glioma Infiltrating Plasmacytoid Dendritic Cells 2019-01-08T13:21:56-05:00 Sharlé Newman imprs@iupui.edu Sreenivasulu Chintala imprs@iupui.edu Mario Henriquez imprs@iupui.edu Mahua Dey imprs@iupui.edu <p><strong>Background and Hypothesis:</strong>&nbsp;Glioblastoma (GBM) is a malignant brain tumor characterized by high tumor heterogeneity and an immunosuppressive tumor microenvironment (TME). Immunomodulation approaches have been investigated, but outcomes remain poor. Several studies describe the functional deregulation of immune cells including, T cells, dendritic cells (DC), and macrophages.&nbsp;Plasmacytoid&nbsp;dendritic cells (pDC), which accumulate in the GBM TME, are shown to have an immunosuppressive phenotype characterized by a lack of IFN-[Symbol]&nbsp;secretion and upregulation of MHC II. MHC II presentation is transcriptionally regulated by several factors produced by tumor cells including, TGFβ, TNFα, and IL10 through the modulation of CIITA, the catalytic component of the&nbsp;enhanceosome. GBM tumor cells secrete several chemokines/cytokines, which may regulate MHC II expression in&nbsp;pDCs. We hypothesize that chemokine CCL21 transcriptionally upregulates MHC II through the activation of CIITA in&nbsp;pDC.&nbsp;&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Experimental Design/Project methods:</strong>&nbsp;We performed experiments using two GBM tumor cells models GL261 and CT2A and used western blot, PCR, immunohistochemistry, immunofluorescence, and flow cytometry to determine the levels of CCL21 and its ligands ACKR3/4 in tumor cells and&nbsp;pDC.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Results:</strong>&nbsp; We observed overexpression of CCL21 in GBM and upregulation of MHCII in tumor associated&nbsp;pDC. We predict that inhibition of CCL21 will lead to downregulation of MHC II in tumor associated&nbsp;pDC&nbsp;which could potentially lead to reversal of the immunosuppressive TME by presenting the antigens to T cells.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Conclusions/Potential Impact:&nbsp;</strong>The results of this study can elucidate novel mechanisms of MHCII regulation and identify CCL21 as a potential therapeutic target for immunotherapy development in GBM.</p> 2018-12-07T13:36:50-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22824 The Degradation and Subcellular Localization of an Oncogenic protein complex in T-cell Leukemia 2019-01-08T13:21:56-05:00 Chiagozie Nwosu imprs@iupui.edu Michael Christy imprs@iupui.edu Justin Layer imprs@iupui.edu Utpal Davé imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>LIM domain Only-2 (LMO2) is a key oncogenic driver of human T-cell acute lymphoblastic leukemia. LMO2 functions as part of a large&nbsp;multisubunit&nbsp;complex that regulates gene expression. LMO2 itself does not bind DNA but it does bind class II basic helix loop helix transcription factors, TAL1 or LYL1,&nbsp; which&nbsp;are also part of the LMO2-associated complex. We recently identified LIM domain binding protein 1 (LDB1) as an obligate LMO2 partner that is required for LMO2 protein stability in T-ALL. We believe the interaction between LDB1 and LMO2 is crucial to understanding the pathogenesis of T-ALL and is a potential therapeutic target for this aggressive leukemia. We hypothesize that in the absence of LDB1, LMO2 is rapidly degraded. Nonetheless, the mechanisms for the localization and degradation of LMO2&nbsp;and its partners&nbsp;have not been fully explored.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>In this study,&nbsp;we&nbsp;analyzed the first order decay of the LMO2-associated complex including&nbsp;LMO2, SSBP2, SSBP3, TAL1, LYL1, and LDB1. We analyzed the subcellular localization of&nbsp;these same&nbsp;proteins&nbsp;distinguishing&nbsp;between the nucleus and the cytoplasm. Our studies were&nbsp;enabled by&nbsp;cloning the HALO tag to the NH2-terminus of these proteins. Fluorescent small molecules such as HALO ligand, R110, were&nbsp;used for intracellular labeling followed by pulse chase analysis via flow cytometry&nbsp;for half-life&nbsp;and&nbsp;imaging by confocal&nbsp;microscopy.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Results:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>We observed a hierarchy of protein stability: LDB1 had the longest half-life, followed by SSBP3, SSBP2, Tal1, LMO2 and Lyl1had the shortest half-lives. Co-expression of LDB1 conferred enhanced&nbsp;staility&nbsp;upon all protein components. All of the protein components studied showed a predominantly nuclear distribution with some in the cytoplasm.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p>The prolonged protein stability of LDB1 allows it to confer enhanced stability to LMO2 and&nbsp;bHLH&nbsp;proteins TAL1 and LYL1. Thus, targeting the assembly of the&nbsp;multisubunit&nbsp;LMO2 complex.</p> 2018-12-07T13:37:26-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22738 Using RNA Editing and ADARs to Increase Cell Sensitivity to Interferon Chemotherapies 2019-01-08T13:21:55-05:00 Eimile Oakes imprs@iupui.edu Obi Nwosu imprs@iupui.edu Pranathi Vadlamni imprs@iupui.edu Heather Hundley imprs@iupui.edu <p><strong>Background and Hypothesis:</strong>&nbsp;During viral infection, viral double stranded RNAs (dsRNAs) are bound by and activate pattern recognition receptors (PRRs). Activated PRRs signal several downstream cellular events, including activating transcription of interferon (IFN). IFN-β can bind to cellular receptors and increase transcription of PRRs, interferon stimulated genes (ISGs), activate Protein Kinase R (PKR) and trigger apoptosis. The ability of IFN to trigger apoptosis makes it a potential chemotherapeutic. However, IFN therapy has had mixed efficacy in inducing tumor cell apoptosis.&nbsp; One mechanism for this failure may be intrinsic mechanisms that prevent dsRNA from binding to and activating PRRs. ADAR1 binds to dsRNA and catalyzes deamination of adenosine to inosine, a process known as RNA editing. Normally, ADAR1 inhibits cellular&nbsp;dsRNAs&nbsp;from initiating the IFN response.&nbsp;Recent studies have shown ADAR1 is overexpressed in several cancers and contributes to oncogenic phenotypes,&nbsp;suggesting inhibition of ADAR1 may increase sensitivity to IFN-β. The Hundley lab recently identified an inhibitor of ADAR1 called ADAR3. ADAR3 has no deaminase activity and is highly expressed in glioblastoma (GBM) tumors. We hypothesize that ADAR3 expressing GBM cells should exhibit a greater antiproliferative effect in response to IFN-b treatment compared to control.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods:</strong>&nbsp;An MTT assay was conducted in which U87 ADAR3 +/- cell lines were exposed to IFN-β after 24 hours. Cell viability was measured for 3 days post-treatment.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Results:</strong>&nbsp;U87 ADAR3 + cells are more sensitive to IFN-β treatment (n=2 biological replicates, p-value= 0.04).<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong>&nbsp;The results suggest a mechanism to enhance IFN therapy for patients with ADAR3 expressing GBM.</p> 2018-12-07T13:37:56-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22739 Patient Perception of Empathy from Emergency Medicine Residents 2019-01-08T13:21:55-05:00 Max Ofoma, MS imprs@iupui.edu Katie Pettit, MD imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><strong>&nbsp;</strong>This project&nbsp;analyzes&nbsp;the effect of&nbsp;years of training and gender of&nbsp;ED&nbsp;providers&nbsp;on&nbsp;patients’ perception of empathy&nbsp;from&nbsp;them. The project will also explore how patient characteristics may&nbsp;impact the&nbsp;patients’&nbsp;perception of empathy from&nbsp;the&nbsp;ED&nbsp;providers.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>It is expected that women providers in their third year of training will exhibit higher scores of empathy. It has been previously demonstrated that white women with&nbsp;a&nbsp;college education have the worst perceptions of empathy&nbsp;from&nbsp;their ED providers.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods:</strong><strong>&nbsp;</strong>Eligible patients from Eskenazi/Methodist Hospital,&nbsp;who have had a CT scan ordered,&nbsp;will be enrolled via convenience sample.&nbsp;Patient perceptions of physician empathy will be assessed&nbsp;via&nbsp;the&nbsp;“Empathy Behavior Survey&nbsp;for Patients”&nbsp;(EBS)&nbsp;and&nbsp;“Jefferson Scale of Patient Perceptions of Physician Empathy” (JSPPPE). Patient demographic data&nbsp;and information about the provider ordering the CT scan&nbsp;will be recorded as well.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><strong>&nbsp;</strong>On the EBS/JSPPE, 1<span data-fontsize="11">st</span>, 2<span data-fontsize="11">nd</span>, and 3<span data-fontsize="11">rd</span>&nbsp;year residents were given scores of 51/31.5, 51/31, and 51.5/33&nbsp;respectively.&nbsp;Male residents were given a median score of 51 on the EBS and 32 on the JSPPPE. Female residents were given a median score of 50.5 and 31 on the JSPPPE.&nbsp;White female patients with a&nbsp;college education&nbsp;gave&nbsp;a score of 50.5 on the EBS and a 32.5&nbsp;on the JSPPPE.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><strong>&nbsp;</strong>Years of training or gender do not seem to have an impact on patient perception of empathy&nbsp;nor do White female patients with a college education.</p> 2018-12-07T13:38:30-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22823 Are signaling pathways inversely regulated in Alzheimer's disease and glioblastoma multiforme? 2019-01-08T13:21:55-05:00 William G. O'Neal imprs@iupui.edu Debomoy K. Lahiri, Ph.D imprs@iupui.edu Mahua Dey, M.D imprs@iupui.edu Ruizhi Wang imprs@iupui.edu <p><strong>Background:</strong>&nbsp;Epidemiological studies suggest an inverse association between cancer and neurodegenerative disorders, including Alzheimer’s disease (AD). AD and cancers, such as glioblastoma&nbsp;multiforme&nbsp;(GBM), are characterized by abnormal but opposing cellular behavior. AD is characterized by accumulation of the processing products&nbsp;of&nbsp;amyloid&nbsp;β&nbsp;(Aβ)&nbsp;and its metabolizing enzymes amyloid&nbsp;precursor protein (APP),&nbsp;β-secretase (or BACE1),&nbsp;and&nbsp;γ-secretase. Our rationale is unraveling cell signaling pathways linking AD and GBM. We&nbsp;hypothesized&nbsp;low-grade gliomas (LGG) and high-grade gliomas (HGG) would have differential expression of neuronal and synaptic markers. Furthermore, protein expression profiles of&nbsp;these markers, APP metabolites, and BACE1 would be different among LGG, HGG, and AD cases.<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Experimental Design or project methods:</strong>&nbsp;Specific neuronal protein markers (e.g., NSE), presynaptic proteins (e.g.,&nbsp;synaptophysin&nbsp;and SNAP25), and post-synaptic proteins (e.g.,&nbsp;PSD-95) have been measured in glioma&nbsp;samples.&nbsp;Characterization are done by Western immunoblotting and ELISA.&nbsp;Protein biomarkers will be analyzed in LGG and HGG of biopsy samples, and the results will be compared with&nbsp;brain samples from&nbsp;AD&nbsp;cases.<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Results:</strong>&nbsp;Using specific primary and secondary antibodies and optimal protein range, we have standardized&nbsp;an&nbsp;immunoblotting procedure to detect&nbsp;our desired proteins&nbsp;in blinded LGG and HGG samples. After&nbsp;unblinding&nbsp;and analyzing results, expression&nbsp;signals&nbsp;will be compared&nbsp;between GBM and&nbsp;AD brain samples.<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Conclusion and</strong><strong>&nbsp;potential impact:</strong>&nbsp;Our results would shed light on diverging and/or shared cell signaling pathways between&nbsp;AD and GBM. In addition, potential impact would be utilizing GBM-derived cultures&nbsp;to&nbsp;test and&nbsp;develop therapeutics for&nbsp;both&nbsp;AD&nbsp;and GBM.</p> 2018-12-07T14:00:41-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22740 Decreased Dynamic Flexibility of Brain Functional Connectivity in Prodromal Alzheimer’s Disease 2019-01-08T13:21:54-05:00 Zachary G. Osborn imprs@iupui.edu Shannon L. Risacher imprs@iupui.edu John D. West imprs@iupui.edu Eileen Tallman imprs@iupui.edu Liana Apostolova imprs@iupui.edu Olaf Sporns imprs@iupui.edu Andrew J. Saykin imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>In neuroimaging, functional connectivity (FC), defined as the correlation between the functional MRI&nbsp;signals&nbsp;of two brain grey matter regions of interest (ROIs), is thought to reflect communication between ROIs. Changes in whole brain FC networks have been detected in Alzheimer’s disease (AD); however, traditional FC networks generated using the entire length of an fMRI scan could miss cognitively relevant fluctuations in FC. Analyzing dynamic patterns of FC within subsets of fMRI scans is hypothesized to enable greater sensitivity to deficits of information transfer and processing in AD compared to static FC.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Project Methods:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Functional MRI data of 58 participants with either subjective cognitive decline (SCD), mild cognitive impairment (MCI), AD, or controls were divided into time windows; the FC within each window provides sequential dynamic FC networks (dFC). Each&nbsp;dFC&nbsp;network was partitioned into subnetworks, e.g. visual or motor, whose member ROIs are strongly interconnected, and the functional flexibility of an ROI was estimated by the number of times it switches subnetworks in a scan.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>The flexibility of the left inferior parietal lobule, right rostral lateral orbitofrontal cortex, and right&nbsp;amyglada/parahippocampal&nbsp;gyrus showed the highest correlations with Montreal Cognitive Assessment scores: r = 0.2516, 0.2480, and 2421, respectively. Although no correlations reached conventional significance (p = 0.0568, 0.0605, and 0.0671, uncorrected), this may reflect low power that should be increased with a planned larger sample.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Potential Impact:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p>Dynamic FC analyses may help clarify the neurophysiological mechanisms underlying cognitive decline, but methodological refinements and higher resolution data are likely needed to realize this potential.</p> 2018-12-07T14:02:23-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22741 Role of Endoscopic Retrograde CholangioPancreatography (ERCP) and Intraductal Secretin Test (IDST) in the Diagnosis of Chronic Pancreatitis (CP) 2019-01-08T13:23:31-05:00 Vitalis C. Osuji imprs@iupui.edu Gail McNulty, RN, BSN, CCRC imprs@iupui.edu Evan Fogel, MD, MSc, FRCP(C) imprs@iupui.edu <p><strong>Background:</strong><strong>&nbsp;</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335551550&quot;:6,&quot;335551620&quot;:6,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>CP may be difficult to diagnose in the early stages when imaging may be normal. An IDST performed at ERCP may further evaluate for CP, with determination of pure pancreatic juice (PPJ) volume and bicarbonate concentration (BC). The optimal collection time for IDST is unknown. We report our experience with the IDST in 447 patients with suspected CP.&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335551550&quot;:6,&quot;335551620&quot;:6,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design:</strong><strong>&nbsp;</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335551550&quot;:6,&quot;335551620&quot;:6,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>IDSTs performed from 2006-2018 were reviewed, with fluid collected at 5-min intervals for 20-60 minutes. Parameters evaluated were PPJ volume, Secretory Flow Rate (SFR), time of peak SFR, maximum BC and time to maximum BC.&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335551550&quot;:6,&quot;335551620&quot;:6,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><strong>&nbsp;</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong><em>Maximum BC</em></strong>&nbsp;was reached by 10-min&nbsp;in&nbsp;59 patients (13.2%); 15-min:&nbsp;207&nbsp;patients (46.3%); 20 min:&nbsp;340&nbsp;patients (76.1%); 25-min:&nbsp;384&nbsp;patients (85.9%); 30-min:&nbsp;421&nbsp;patients (94.1%).&nbsp;<strong><em>Peak SFR&nbsp;</em></strong>was reached by 10-min&nbsp;in&nbsp;92 patients (20.6%); 15-min:&nbsp;177&nbsp;patients (39.6%); 20-min:&nbsp;240&nbsp;patients (53.7%); 25-min:&nbsp;284&nbsp;patients (63.5%); 30-min: 323&nbsp;patients (72.3%). Final diagnosis (normal vs. CP) for both SFR and BC was determined by 20-min (i.e. in CP pts, either the SFR or BC was low (SFR &lt;3ml/min, BC &lt;105mEq/L) and remained low throughout collection, or normal (&gt;3ml/min and &gt;105mEq/L) within the first 20-min. Further collection did not change the diagnosis.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335551550&quot;:6,&quot;335551620&quot;:6,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusio</strong><strong>n</strong><strong>:&nbsp;</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>At IDST, a 20-minute collection period is necessary to categorize patients into normal or suspected CP groups.&nbsp;A study in control patients (no suspicion of CP) to validate these data is currently underway.&nbsp;&nbsp;</p> 2018-12-07T00:00:00-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22742 Fecal Bile Acids and Fecal Short Chain Fatty Acids in Patients with Irritable Bowel Syndrome and Control Volunteers 2019-01-08T13:21:54-05:00 Chirag Patel imprs@iupui.edu Carolyn Lockett imprs@iupui.edu Huiping Xu imprs@iupui.edu Andrea Shin imprs@iupui.edu <p><strong>Background and&nbsp;</strong><strong>Aims</strong><strong>:</strong>&nbsp;Fecal&nbsp;bile acids (BAs), short chain fatty acids (SCFAs), and gut microbiome may&nbsp;be implicated in&nbsp;irritable bowel syndrome (IBS)&nbsp;pathophysiology.&nbsp;Our aim was to compare&nbsp;fecal organic acids&nbsp;between IBS&nbsp;with constipation&nbsp;(IBS-C), IBS&nbsp;with diarrhea&nbsp;(IBS-D), and&nbsp;controls.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Methods:</strong><strong>&nbsp;</strong>Stool samples were collected from&nbsp;17 controls,&nbsp;5 IBS-C,&nbsp;and&nbsp;5 IBS-D&nbsp;volunteers&nbsp;during a 4-day&nbsp;high fat&nbsp;diet.&nbsp;Aliquots&nbsp;were stored for future analysis of the fecal microbiota.&nbsp;Fecal&nbsp;SCFA and BA&nbsp;analyses&nbsp;were&nbsp;conducted at the Metabolite Profiling Facility at Purdue University and Laboratory Medicine and Pathology at Mayo Clinic.&nbsp;We compared&nbsp;SCFA and BA&nbsp;levels&nbsp;among&nbsp;groups using the Wilcoxon rank sum test. Gamma and linear regression were used to compare SCFAs&nbsp;and BAs&nbsp;adjusting for age and body mass index&nbsp;(BMI).<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><strong>&nbsp;</strong>Fecal acetate&nbsp;levels (mean+SD,&nbsp;µg/mg) were&nbsp;higher&nbsp;in IBS-C (11.3±7) than&nbsp;in&nbsp;controls&nbsp;(6.1±3.3)&nbsp;or&nbsp;IBS-D (7.7±2), although not statistically significant (p=0.19).&nbsp;Total fecal BAs (median [IQR], %) were higher in IBS-D (675 [484-778]) than in controls (342 [130-640])&nbsp;or&nbsp;IBS-C (321.5 (34.5-718); however,&nbsp;differences were not significant. No significant differences were observed&nbsp;in BAs&nbsp;or SCFAs&nbsp;between groups in multivariate&nbsp;analyses.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion:</strong><strong>&nbsp;</strong>We are unable to&nbsp;show&nbsp;significant differences&nbsp;in organic acid levels&nbsp;in&nbsp;IBS&nbsp;and&nbsp;controls.&nbsp;Lack of association&nbsp;may be due to&nbsp;small sample&nbsp;size. Future&nbsp;investigation&nbsp;of&nbsp;larger patient numbers with&nbsp;incorporation of transit and microbiome analyses may shed further light on the role of organic acids in&nbsp;IBS&nbsp;to identify new&nbsp;biomarkers&nbsp;and&nbsp;treatment targets.</p> 2018-12-07T14:04:01-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22825 Combined inhibition of Bruton’s Tyrosine Kinase (BTK) and Phosphoinositide 3-kinase (PI3K) p110δ improves monocytosis and splenomegaly in a JMML Mouse Model 2019-01-08T13:21:54-05:00 Roshni Patel imprs@iupui.edu Baskar Ramdas imprs@iupui.edu Lisa Deng imprs@iupui.edu Victoria Jideonwo-Auman imprs@iupui.edu Reuben Kapur imprs@iupui.edu <p><strong>Background and Hypothesis:&nbsp;</strong>Juvenile&nbsp;myelomonocytic&nbsp;leukemia (JMML) is an aggressive, childhood leukemic disorder for which there are no efficacious chemotherapeutics. Gain-of-function (GOF) mutations in the SHP2 phosphatase oncogene,&nbsp;<em>Ptpn11</em>, are the most common associated mutations. In hematopoietic cells, these mutations lead to increased AKT and ERK&nbsp;activation,&nbsp;which results in&nbsp;hyperproliferation of myeloid cells.&nbsp;Clinically, this manifests as monocytic leukocytosis and marked splenomegaly with the consequence of severe thrombocytopenia. Previously, this lab has shown that pharmacological inhibition of p110d, the hematopoietic-specific catalytic subunit&nbsp;of&nbsp;PI3K, moderates&nbsp;monocytosis&nbsp;and splenomegaly in a JMML mouse model with a SHP2 GOF mutation (E76K mice). Additionally, BTK has been identified as a potential therapeutic target as it cooperates with PI3K to increase activation of AKT and ERK in myeloid cells.&nbsp;Using a dual-hit approach of targeting both PI3K p110d and BTK may serve as a valuable treatment design for JMML.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods:&nbsp;</strong>We&nbsp;have treated E76K mice with a combination of&nbsp;20mg/kg&nbsp;ACP319, a&nbsp;PI3K p110d-specific inhibitor, and 20mg/kg&nbsp;acalabrutinib, a&nbsp;BTK-specific inhibitor,&nbsp;via oral gavage&nbsp;twice daily&nbsp;for 21 days and&nbsp;performed hematopoietic analysis including&nbsp;the&nbsp;degree of&nbsp;splenomegaly,&nbsp;monocytosis,&nbsp;and thrombocytopenia.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:&nbsp;</strong>The<strong>&nbsp;</strong>combination treatment scheme significantly decreased&nbsp;monocytosis&nbsp;and ameliorated thrombocytopenia compared to vehicle treated mice.&nbsp;Furthermore, splenomegaly was significantly reduced in the combination-treated mice compared to vehicle.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:&nbsp;</strong>Combination chemotherapy with PI3K p110d- and BTK-specific inhibitors&nbsp;profoundly corrects disease state hallmarks of JMML, and may warrant&nbsp;further&nbsp;clinical investigation of efficacy.</p> 2018-12-07T14:04:39-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22743 Surveying ADR knowledge and practices among US gastroenterologists 2019-01-08T13:21:54-05:00 Michael Peng imprs@iupui.edu Douglas Rex, MD, MACG imprs@iupui.edu <p><strong>Background:</strong>&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>The adenoma detection rate (ADR) is of primary importance to the quality of screening colonoscopy. An online survey was conducted to assess knowledge and practices on ADR.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Methods:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Paid questionnaire distributed by email. Eligible respondents were board certified gastroenterologists who perform &gt;80 colonoscopies per month with 3 to 35 years after fellowship.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>39% were unaware that ADR applies only to screening colonoscopies and 76% incorrectly answered that ADR includes sessile serrated polyps/adenomas.&nbsp; 51% of respondents incorrectly believe the threshold is set at 25% because 25% is a national ADR average. Many also believe the threshold depends on the patient population (current evidence suggests adjusting ADR for factors other than age and sex is unnecessary). 75% ranked ADR as highly important.&nbsp;80% reported tracking ADR. A busy practice was the most common reason for not tracking ADR. Caps, chromoendoscopy, and good bowel preparation were viewed as valuable for improving ADR (this is true except for caps). HD colonoscopes and education were considered less valuable (although evidence suggests HD and education are associated with improved ADR). 57% reported not sharing ADR information with their&nbsp;patients, and 59% reported&nbsp;no&nbsp;patients in the past 6 months asking&nbsp;for&nbsp;their&nbsp;ADR.</p> <p><strong>Conclusio</strong><strong>n</strong><strong>:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p>The importance of ADR as a validated quality measure is well understood, but there are misconceptions among gastroenterologists regarding the definition and measurement of ADR and which methods are proven to increase ADR.&nbsp; Patients are having very little impact on ADR measurement.</p> 2018-12-07T14:05:40-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22744 Minimally Invasive, Non-Terminal In Vivo Muscle Testing of a Porcine Tibia Fracture Model 2019-01-08T13:21:53-05:00 Alexander W. Peters imprs@iupui.edu Benjamin T. Corona imprs@iupui.edu Anthony J. Milto imprs@iupui.edu Aamir Tucker imprs@iupui.edu Alex Brinker imprs@iupui.edu Michael Savaglio imprs@iupui.edu Gremah Adam imprs@iupui.edu Venkateswaran Ganesh imprs@iupui.edu Zachary Gunderson imprs@iupui.edu Paul Childress imprs@iupui.edu Roman M. Natoli imprs@iupui.edu Todd O. McKinley imprs@iupui.edu Melissa A. Kacena imprs@iupui.edu <p><strong>Background and Hypothesis</strong>:&nbsp;Soft tissue injury surrounding tibia fractures is a key determinant of surgical care decisions and healing outcomes.&nbsp;We&nbsp;have established&nbsp;a porcine tibia&nbsp;fracture model with a&nbsp;corresponding volumetric muscle loss (VML) injury in the adjacent peroneus tertius (PT) muscle. Herein, we&nbsp;test the&nbsp;hypothesis that tibia fracture without VML induces an initial strength deficit that recovers within three months post-injury, while VML injuries present chronic strength deficits.&nbsp;<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods</strong><strong>:</strong>&nbsp;15&nbsp;castrated Yucatan minipigs pigs will be evaluated in the following&nbsp;groups: Tibia defect (TD)-only,&nbsp;TD+small&nbsp;VML,&nbsp;and&nbsp;TD+large&nbsp;VML. To date, 12&nbsp;have undergone injury, and 3 have completed&nbsp;the study (TD-only, n=2;&nbsp;&nbsp;TD+small&nbsp;VML, n=1).&nbsp;<span data-ccp-props="{}">&nbsp;</span></p> <p><em>In vivo</em>&nbsp;muscle testing of the anterior compartment of the lower hindlimb was performed before and 1, 2,&nbsp;and 3 months post-injury.<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>R</strong><strong>esults</strong>: Before injury the non-operative and operative limbs had similar peak muscle strength (11.8±1.0 vs. 10.8±0.6 Nm; p=0.42), and non-operative limb strength did not change during the study (ANOVA p=.89). Relative to pre-injury values, the tibia defect with VML injury presented 71, 77, and 79% strength loss, while the tibia defect-only limbs presented 46, 60, and 48% strength loss at 1, 2, and 3 months post-injury, respectively.<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Conclusion</strong><strong>&nbsp;and Potential Impact</strong><strong>:</strong>&nbsp;The data are limited by low sample sizes&nbsp;as this project is ongoing.&nbsp;Preliminary data do not appear to support the hypothesis, as limbs with TD-only presented persistent&nbsp;strength deficits, though potentially of lesser magnitude than VML injured limbs. The mechanism of strength loss following TD-only may be related to disuse.</p> 2018-12-07T14:06:16-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22745 Outcome of Pediatric Emergency Point-of-Care Ultrasound (POCUS) for Management of Skin and Soft Tissue Infection Prior to Ultrasound Program Implementation 2019-01-08T13:21:53-05:00 Whitney Phillips, BS imprs@iupui.edu Benjamin Nti, MD, MSc imprs@iupui.edu <p><strong>Background and Hypothesis:</strong>&nbsp;Point-of-care ultrasound (POCUS) is&nbsp;underutilized for evaluation of skin and soft tissue infections (SSTI) in the pediatric emergency department (ED).&nbsp;This study seeks to determine the utilization of POCUS compared to formal&nbsp;radiology&nbsp;ultrasound for SSTI in the pediatric ED&nbsp;prior to an ultrasound program implementation.&nbsp;We hypothesize that&nbsp;POCUS utilization will be low but can&nbsp;lead to a decreased length of stay&nbsp;(LOS)&nbsp;and cost for patients with SSTI.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods:</strong>&nbsp;This is a retrospective&nbsp;EMR&nbsp;chart review covering pre-implementation (July 2016-June 2017) and post-implementation (July 2018-June 2019) of a POCUS&nbsp;program curriculum. Patients&nbsp;(&lt;18 years old)&nbsp;were included based on screening for diagnoses via the&nbsp;international classification of diseases 9<span data-fontsize="11">th</span>&nbsp;and 10<span data-fontsize="11">th</span>&nbsp;revision codes for abscesses and cellulitis.&nbsp;We excluded patients who required admission&nbsp;and subspecialty consult&nbsp;or had other non-SSTI evaluation.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong>&nbsp;Pre-Implementation period included 160&nbsp;patients&nbsp;who&nbsp;met inclusion&nbsp;and exclusion&nbsp;criteria.&nbsp;Of these, 16 (10%) received&nbsp;POCUS&nbsp;evaluation and 8 (5%) received a radiology image evaluation.&nbsp;The majority of patients had cellulitis&nbsp;(80%) when compared to abscess (20%). The average LOS for&nbsp;POCUS&nbsp;ultrasound was 173&nbsp;minutes&nbsp;compared to 304&nbsp;minutes&nbsp;for radiology evaluation. The total cost for visit was $3,503&nbsp;for patients evaluated by&nbsp;POCUS&nbsp;compared to $8,875.56 for&nbsp;patients who received&nbsp;radiology imaging.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong>&nbsp;Taken together,&nbsp;the pre-implementation assessment of&nbsp;POCUS&nbsp;utilization&nbsp;in the pediatric emergency department was low but associated&nbsp;with&nbsp;decreased LOS&nbsp;and&nbsp;lower total ED cost&nbsp;when applied to SSTI management.</p> 2018-12-07T14:06:48-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22746 Anxiety Screening in the Emergency Department 2019-01-08T13:21:53-05:00 Michelle Pinto imprs@iupui.edu Paul Musey, Jr., MD imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Preliminary research completed in the Indiana University Health Methodist Emergency Department (ED) determined that the prevalence of undetected or unaddressed abnormal anxiety levels in patients with low-risk chest pain was greater than 45%. This subset was noted to have abnormal anxiety symptoms that persisted following visits and increased ED recidivism. We hypothesize that the prevalence of abnormal anxiety in the general ED population will be similar to the subset of patients with low-risk chest pain shown previously.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Methods:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>We enrolled a convenience sample of adult patients with non-psychiatric chief complaints who presented to IUH Methodist and&nbsp;Eskenazi&nbsp;Emergency Departments. Participants were assessed for abnormal anxiety levels using the Generalized Anxiety Disorder 7-item Scale (GAD-7) and the Hospital Anxiety Depression Scale (HADS). Subjects will also complete these assessment tools at 30-days post-enrollment via phone or&nbsp;REDCap&nbsp;survey. Data regarding ED disposition, discharge diagnosis, and ED utilization over the previous 12 months and the 30 days post-enrollment will be collected from the electronic medical record (EMR).<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Over four weeks, 108 patients were screened and 37 gave informed consent and were enrolled. Preliminary analysis shows that 21 subjects (56%) had a GAD-7 score ≥10, indicating abnormal anxiety levels. Full data analysis including comparison of HADS and GAD-7 scores will take place after 50 subjects have been enrolled, completed their 30-day follow-up surveys, and EMR review has taken place.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Given data regarding ED visits in patients with low-risk chest pain, identification of anxiety and referral may reduce ED utilization.</p> 2018-12-07T14:07:33-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22747 Identification of genes and molecular pathways involved in a C. elegans model of neuroborreliosis 2019-01-08T13:21:53-05:00 Ruben Prado imprs@iupui.edu Gai-Linn Bessing imprs@iupui.edu Nathaniel Snyder imprs@iupui.edu Gurpalik Singh imprs@iupui.edu Frank Yang imprs@iupui.edu Richard Nass imprs@iupui.edu <p><strong>Background</strong><strong>&nbsp;and Hy</strong><strong>p</strong><strong>o</strong><strong>thesis</strong>:&nbsp;Lyme disease is caused by the&nbsp;spirochaete&nbsp;bacteria from the&nbsp;<em>Borrelia</em>&nbsp;species.&nbsp;Recent studies suggest that Lyme disease may be associated with dementia, brain atrophy, and protein aggregates that may be associated with the development of neurodegenerative diseases such as Parkinson’s&nbsp;disease (PD)&nbsp;and&nbsp;Alzheimers&nbsp;disease&nbsp;(AD).&nbsp;The molecular basis of the&nbsp;<em>Borrelia</em>-associated innate immune response and associated neuropathology is poorly defined.&nbsp;&nbsp;A significant hindrance in dissecting these molecular components is the lack of facile in vivo genetic models to explore the mechanisms involved in the neuropathology. Here we hypothesize that the nematode&nbsp;<em>C.&nbsp;</em><em>elegans</em>&nbsp;will be a useful model for&nbsp;<em>Borrelia</em>-associated innate immunity and neuropathology.<span data-ccp-props="{&quot;335551550&quot;:6,&quot;335551620&quot;:6,&quot;335559739&quot;:200}">&nbsp;</span></p> <p><strong>Project Methods</strong>: We utilized transcriptional reporters, transgenic animals, neuronal morphology analysis,&nbsp;RNAi,&nbsp;host defense pathways,&nbsp;AD- and PD-associated pathologies, and behavior assays to determine the effect that&nbsp;<em>Borrelia</em>&nbsp;has on&nbsp;<em>C.&nbsp;</em><em>elegans</em>&nbsp;viability.<span data-ccp-props="{&quot;335551550&quot;:6,&quot;335551620&quot;:6,&quot;335559739&quot;:200}">&nbsp;</span></p> <p><strong>Results</strong>:&nbsp;<em>C.&nbsp;</em><em>elegans</em><em>&nbsp;</em>can be infected and survive using&nbsp;<em>Borrelia</em>&nbsp;as a food source, and the bacteria can induce highly conserved innate immune response pathways, and exacerbate PD-associated dopamine neuronal death&nbsp;in&nbsp;human A53T&nbsp;-synuclein-expressing animals.&nbsp;<em>C.&nbsp;</em><em>elegans</em>&nbsp;models expressing AD-associated human A&nbsp;1-42&nbsp;also&nbsp;show significant movement&nbsp;defects&nbsp;and&nbsp;increased protein aggregates when exposed to&nbsp;<em>Borrelia</em>.<span data-ccp-props="{&quot;335551550&quot;:6,&quot;335551620&quot;:6,&quot;335559739&quot;:200}">&nbsp;</span></p> <p><strong>Conclusions and Potential Impact</strong>: This study further characterizes a novel genetic model for&nbsp;<em>Borrelia</em>-associated innate immunity and neuropathology.&nbsp;Incorporating&nbsp;<em>C.&nbsp;</em><em>elegans</em>&nbsp;genetic screens, this model&nbsp;should allow us to identify mediators&nbsp;of the&nbsp;<em>Borrelia</em>-associated&nbsp;pathologies&nbsp;that should facilitate the identification of molecular pathways and potential therapeutic targets.</p> 2018-12-07T14:08:09-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22748 Immune regulation of neuronal injury and repair by observing T cell activation 2019-01-08T13:21:52-05:00 Eric J. Regele imprs@iupui.edu Elizabeth M. Runge imprs@iupui.edu Felicia M. Kennedy imprs@iupui.edu Virginia M. Sanders imprs@iupui.edu Kathryn J. Jones imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>It is unknown how the&nbsp;immune system maintains the majority of facial motoneuron (FMN) survival after axotomy.&nbsp;IL-10 cytokine&nbsp;is necessary for&nbsp;FMN survival and CD4<span data-fontsize="11">+</span>&nbsp;T cells are activated and play a critical role in survival, but do not produce IL-10.&nbsp;It was proposed that the source of IL-10 resides in the CNS; however, it is possible that antigen presenting cells (APC) produce IL-10 which&nbsp;activate CD4<span data-fontsize="11">+</span>&nbsp;T cells to a neuroprotective phenotype.&nbsp;The regulation of IL-10 receptors (IL-10R) in immunodeficient compared to wild-type (WT) mice in the facial nucleus was studied in this experiment, as well as the possibility of&nbsp;the PNS producing&nbsp;IL-10.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>To study&nbsp;APC’s role in motoneuron survival,&nbsp;we&nbsp;transferred WT&nbsp;whole splenocytes into global IL-10 knock out&nbsp;(KO)&nbsp;mice prior to&nbsp;axotomy.&nbsp;To&nbsp;study&nbsp;IL-10R&nbsp;gene expression,&nbsp;immunodeficient RAG-2 KO&nbsp;mice received&nbsp;WT or IL-10R<span data-fontsize="11">-/-&nbsp;</span>CD4<span data-fontsize="11">+&nbsp;</span>T cells&nbsp;prior to axotomy.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>qPCR revealed that WT mice upregulate IL-10R&nbsp;after axotomy, whereas&nbsp;RAG-2&nbsp;KO&nbsp;mice&nbsp;had&nbsp;decreased expression&nbsp;comparatively.&nbsp;RAG-2&nbsp;mice who&nbsp;received WT CD4<span data-fontsize="11">+&nbsp;</span>T cells&nbsp;transfer&nbsp;restored IL-10R comparable to WT values.IL-10R was rescued in RAG-2 mice after the adoptive transfer of WT CD4<span data-fontsize="11">+</span>T cells.&nbsp;When&nbsp;IL-10R<span data-fontsize="11">-/-</span>&nbsp;CD4<span data-fontsize="11">+&nbsp;</span>cells were&nbsp;transferred into RAG-2 mice,&nbsp;IL-10R&nbsp;values were restored;&nbsp;however,&nbsp;these&nbsp;T cells&nbsp;were unable to rescue FMN survival.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>If&nbsp;WT&nbsp;whole&nbsp;splenocytes&nbsp;transferred into&nbsp;global IL-10 KO mice&nbsp;rescue&nbsp;FMN survival,&nbsp;it&nbsp;implies that APC&nbsp;play a role in producing IL-10. If they&nbsp;cannot mediate&nbsp;rescue, then&nbsp;peripheral IL-10 is unlikely&nbsp;sufficient&nbsp;for FMN survival.&nbsp;CD4<span data-fontsize="11">+&nbsp;</span>T cells regulate central IL-10R response&nbsp;and&nbsp;must&nbsp;respond to IL-10&nbsp;to mediate FMN survival.&nbsp;The&nbsp;transfer of whole splenocytes provides&nbsp;APCs&nbsp;capable of producing IL-10 and CD4<span data-fontsize="11">+&nbsp;</span>T cells capable of responding to IL-10.&nbsp;</p> 2018-12-07T14:08:52-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22749 The risk of bleeding following therapeutic endoscopy is low in patients with cirrhosis 2019-01-08T13:21:52-05:00 Kathryn Reinhart imprs@iupui.edu Parkpoom Phatharacharukul imprs@iupui.edu Eric Orman imprs@iupui.edu <p><strong>Background</strong>:&nbsp;Patients with cirrhosis may be at increased risk of bleeding after invasive procedures due to defects in coagulation;&nbsp;however&nbsp;the bleeding risk following therapeutic endoscopy remains poorly understood. We aimed to determine the incidence and risk factors&nbsp;for post-procedural bleeding for patients with cirrhosis undergoing therapeutic endoscopy.</p> <p><strong>Methods</strong>: We performed a retrospective cohort study of patients undergoing three common endoscopic procedures (colonoscopic&nbsp;polypectomy, endoscopic&nbsp;variceal&nbsp;ligation, and biliary&nbsp;sphincterotomy) at Indiana University Hospital between 2007 and 2014. Clinical and procedural data were collected, including complications in the 30 days following the&nbsp;proceduress.<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Results</strong>: We identified 447 procedures: 128 polypectomies, 63&nbsp;sphincterotomies, and 256&nbsp;variceal&nbsp;ligations. The incidence of bleeding was 2% (4 polypectomies, 1&nbsp;sphincterotomy, and 4&nbsp;variceal&nbsp;ligations) after a median of 4.5 days. .&nbsp;Prophlactic&nbsp;platelet transfusions were provided to 11 patients and plasma was transfused in 17 patients. Of those who received prophylactic transfusions, only one bled (post-polypectomy despite prophylactic&nbsp;hemoclip&nbsp;placement). The patients that bled had a median INR of 1.48 which was slightly elevated compared to the overall median INR 1.26. Post-polypectomy bleeding occurred following removal of fairly large polyps (8, 9, 10, 25 mm) compared to the median overall polyp size of 5 mm.&nbsp;<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Conclusion</strong>: The incidence of bleeding for patients with cirrhosis undergoing therapeutic endoscopy is low. More data on post-procedural bleeding are needed to determine risk factors and to inform appropriate prophylactic measures. These data may be used to guide clinicians in counseling patients prior to these procedures.</p> 2018-12-07T14:09:38-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22750 Early Pain, Narcotic Use, and Functional Recovery in Aseptic Revision Total Knee Arthroplasty Performed with Morphine Spinal Analgesia versus Fentanyl Spinal Analgesia with Adductor Canal Block 2019-01-08T13:21:52-05:00 Justin Rice, BA imprs@iupui.edu Amer Mohiuddin, BS imprs@iupui.edu Trent Nielson imprs@iupui.edu Mary Ziemba-Davis, BA imprs@iupui.edu R. Michael Meneghini, MD imprs@iupui.edu <p><strong>Background and Hypothesis:</strong>&nbsp;There has been a trend away from intrathecal morphine for perioperative pain control during and after total knee arthroplasty (TKA) and&nbsp;it&nbsp;has been replaced by shorter-acting non-morphine spinals combined with adductor canal block (ACB) regional analgesia.&nbsp;The purpose of this study is to compare pain control and side-effects between morphine intrathecal alone and fentanyl spinal with ACB in revision TKA.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Project Methods:</strong><strong>&nbsp;</strong>Prospectively collected data on 167 consecutive aseptic revision TKAs performed&nbsp;by a single surgeon&nbsp;between 2010 and 2017 were&nbsp;retrospectively&nbsp;reviewed. &nbsp;Inpatient pain, narcotic use, functional milestones, complications, and four-month&nbsp;patient reported&nbsp;outcomes&nbsp;were&nbsp;compiled for the two cohorts&nbsp;(110 fentanyl/ACB and 57 morphine&nbsp;cases).<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><strong>&nbsp;</strong>Average age&nbsp;(<em>p</em>=0.66) and BMI (<em>p</em>=0.542) were equivalent in the two cohorts (<em>p</em>=0.542).&nbsp;Fentanyl/ACB patients&nbsp;gained more&nbsp;range-of-motion (ROM)&nbsp;by 4-month follow-up (<em>p</em>=0.051) than morphine patients.&nbsp;&nbsp;However,&nbsp;fentanyl/ACB&nbsp;patients had higher average pain scores (<em>p</em>=0.006), consumed&nbsp;opioids&nbsp;earlier&nbsp;(<em>p</em>&lt;0.001),&nbsp;and consumed more opioids&nbsp;(<em>p</em>&lt;0.001) on postoperative&nbsp;day one. Morphine analgesia was associated with more nausea/vomiting (<em>p</em>=0.001) and pruritus (<em>p</em>=0.00001).<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion</strong><strong>&nbsp;and Potential Impact</strong><strong>:</strong><strong>&nbsp;</strong>Morphine&nbsp;intrathecal&nbsp;patients reported&nbsp;less&nbsp;inpatient&nbsp;pain and consumed less opioid, which&nbsp;most likely reflects morphine’s longer half-life. Improved&nbsp;4-month&nbsp;ROM in the fentanyl/ACB group may reflect the quadriceps-sparing nature of ACBs.&nbsp;It is also possible&nbsp;that&nbsp;the&nbsp;operative field in revision TKA extends&nbsp;beyond the&nbsp;sensory protection&nbsp;of ACB.&nbsp;&nbsp;Further research is required to elucidate the relative impact of ACBs on&nbsp;primary vs.&nbsp;revision procedures.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> 2018-12-07T14:10:16-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22751 Comparison of two techniques using EUS guided liver biopsies via 19g core biopsy needle to obtain optimal core specimen in benign disease 2019-01-08T13:21:52-05:00 Brad Rumancik imprs@iupui.edu Sharwani Kota imprs@iupui.edu Judy Irvin imprs@iupui.edu Christina Zelt imprs@iupui.edu Michael Mirro imprs@iupui.edu Neil Sharma imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Endoscopic ultrasound (EUS) guided fine-needle biopsy (FNB) to obtain core liver&nbsp;specimen&nbsp;is&nbsp;shown&nbsp;to be effective and safe. However, prospective data is limited regarding EUS-FNB in non-malignant liver disease. This study evaluates two EUS-FNB techniques&nbsp;with the hypothesis that the&nbsp;modified wet suction (MWS)&nbsp;technique will produce greater pathological yield than the&nbsp;slow pull (SP)&nbsp;technique&nbsp;in patients with non-malignant liver disease.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>In this prospective, randomized controlled trial we are evaluating efficacy and safety&nbsp;of EUS-FNB techniques (MWS versus SP) in&nbsp;patients with initial indication for an upper endoscopy plus need for a liver biopsy&nbsp;to assess non-malignant disease. The primary outcome is pathological yield defined as number of complete portal tracts (CPTs), specimen length, and fragmentation. Secondary outcomes include pathological yield between two specimen processing techniques, pathological yield between left versus right liver lobe biopsy, time for biopsy technique, and complications.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>For this interim analysis, 8 patients (5 received MWS and 3 received SP) out of a projected total of 360 patients are enrolled. Independent t-test analysis reveals no statistical difference between CPTs (P=0.56), specimen length (P=0.12), and fragmentation (P=0.16). No differences are found between any secondary outcomes, and there have been no&nbsp;biopsy-related&nbsp;complications.   <span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>This underpowered interim analysis reveals no statistical difference in primary or secondary outcomes between MWS versus SP technique. The current results for both groups are consistent with specimen adequacy criteria determined by American Association for the Study of Liver Disease.</p> 2018-12-07T14:11:07-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22753 Attitudes toward Contraception Initiation in the Emergency Department among Providers and Patients 2019-01-08T13:21:52-05:00 Nathan VanderVinne, DO imprs@iupui.edu Sydney Ryckman, BS imprs@iupui.edu Lynn Coy, DO imprs@iupui.edu Kimberly Swartz, MD, JD imprs@iupui.edu Caitlin Bernard, MD imprs@iupui.edu Jeffrey Kline, MD imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><strong>&nbsp;</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>In 2011, 45% of 6.1 million pregnancies were unintended. Women between the ages of&nbsp;20-24, those with lower education, lower income, and of African American descent had higher rates&nbsp;of unintended pregnancies.<span data-fontsize="11">i</span>&nbsp;In 2014, there were 25.9 million visits&nbsp;to the ED&nbsp;by&nbsp;women under the age of 24.<span data-fontsize="11">ii</span>&nbsp;Intervention within the Emergency Department to assess fertility status and provide contraception when appropriate has the potential to help reduce the number of mistimed and unwanted pregnancies.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>This study aims to assess the attitudes toward providing contraception within the Emergency Department&nbsp;via surveys.&nbsp;The provider survey will be sent through a large national list serve; the patient survey&nbsp;was given to&nbsp;women 18-45 years old within the Emergency Departments of a large county hospital and inner-city urban hospital.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>So far,&nbsp;200 surveys were collected. 32&nbsp;women were planning to get&nbsp;pregnant within the next year, 135&nbsp;were not attempting to get pregnant,&nbsp;13 were unsure, and 20 could not get pregnant. The number of women&nbsp;who were unsure or did not want&nbsp;to get pregnant&nbsp;totaled to 148; out of these women,&nbsp;62% showed interest in receiving access to birth control within the ED.&nbsp;We still plan to do more data analysis, including&nbsp;how many of these women are currently using birth control&nbsp;and&nbsp;demographic analysis looking at race, education level, and relationship status.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p>If there is substantial interest, we will then conduct a study to initiate contraception within the ED.&nbsp;This will hopefully contribute to reducing&nbsp;the unintended pregnancy rate.</p> 2018-12-07T14:11:52-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22754 Utilizing Citizen Science to Reverse the Current Lead Testing Paradigm: Development of a Scalable, Low-cost Home Lead Test Kit 2019-01-08T13:21:51-05:00 Katlyn Sawyer imprs@iupui.edu Chris Knaub imprs@iupui.edu Meghanne Tighe imprs@iupui.edu Danielle Forbes imprs@iupui.edu Claire Marks imprs@iupui.edu Lane Nicolay imprs@iupui.edu Citlali Gutierrez imprs@iupui.edu Mike Dowd imprs@iupui.edu Maggie Bielski imprs@iupui.edu Matthew Sisk imprs@iupui.edu Michelle Ngai imprs@iupui.edu Marya Lieberman imprs@iupui.edu Graham Peaslee imprs@iupui.edu Heidi Beidinger imprs@iupui.edu <p><strong>Background:</strong><strong>&nbsp;</strong>The&nbsp;Center for Disease Control&nbsp;recommends&nbsp;case management begin at a blood lead level&nbsp;of 5 μg/dL,&nbsp;yet&nbsp;Indiana does not take action until a&nbsp;blood lead level&nbsp;of&nbsp;10 μg/dL.&nbsp;Low levels of lead&nbsp;can&nbsp;cause&nbsp;irreversible neurological damage in children.&nbsp;The&nbsp;goal of this study was to design a&nbsp;scalable, low-cost Home Lead Test Kit to proactively find lead in homes.<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Methods:</strong><strong>&nbsp;</strong>Individuals were recruited&nbsp;through community partnerships,&nbsp;community lead testing&nbsp;events, and flyers.&nbsp;Qualitative&nbsp;data was recorded&nbsp;during home visits&nbsp;as participants&nbsp;used the kit. An x-ray fluorescence analyzer&nbsp;was used&nbsp;in the field and&nbsp;laboratory&nbsp;to&nbsp;analyze lead levels of samples.&nbsp;Results were blinded during the analysis.<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Results:</strong>&nbsp;To date, 40&nbsp;homes have been recruited, and 20&nbsp;have been completed.&nbsp;The average completion time of the kit was&nbsp;23.45&nbsp;minutes.&nbsp;&nbsp;Of the 8&nbsp;pre-1950&nbsp;homes&nbsp;100% had elevated lead results, of the 7&nbsp;1950-1978 homes 43% had elevated lead results, and of&nbsp;the 5&nbsp;post 1978 homes 0% had elevated lead results.&nbsp;<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Conclusion</strong><strong>&nbsp;and Potential Impact</strong><strong>:</strong><strong>&nbsp;</strong>The study is ongoing.&nbsp;Preliminary results support the hypothesis that&nbsp;pre-1950 homes have a high risk of lead exposure, and&nbsp;post 1978 homes have minimal to no levels of lead. Feedback from study participants regarding kit usability has been positive.&nbsp;Future plans are&nbsp;to produce a kit to be scaled up in St. Joseph County with the goal of a statewide model. This kit may allow citizens to identify lead hazards to prevent children from lead exposure.&nbsp;</p> 2018-12-07T14:12:31-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22762 Increasing Adolescents’ Access to the HIV Continuum of Care: Development of a Screening Tool for Medical Legal Partnerships 2019-01-08T13:21:51-05:00 Anna C. Scalzo imprs@iupui.edu Amy L. Gilbert, JD, MPH imprs@iupui.edu <p><strong>Background:&nbsp;</strong>Research&nbsp;has shown&nbsp;that at-risk youth are not being reached by HIV testing&nbsp;efforts&nbsp;and&nbsp;are&nbsp;encountering barriers at other points along the HIV Continuum of Care (CoC). Legal remedies often exist for youth and their families in addressing barriers to&nbsp;the HIV&nbsp;CoC.&nbsp;The purpose of this study was&nbsp;to develop a targeted screening tool for identifying unmet health-harming legal needs that create barriers to the HIV&nbsp;CoC&nbsp;at the level of individual youth,&nbsp;to be used&nbsp;in clinics with Medical Legal Partnerships (MLPs)&nbsp;designed to address such barriers through legal intervention.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Project Methods</strong><strong>:&nbsp;</strong>A literature&nbsp;search&nbsp;was completed&nbsp;to investigate&nbsp;if validated screening questions&nbsp;already&nbsp;existed for the 10 areas of adolescent&nbsp;health-harming&nbsp;legal needs&nbsp;previously identified from&nbsp;qualitative interviews with at-risk youth&nbsp;and care providers. A focus&nbsp;group&nbsp;of&nbsp;legal professionals was conducted to&nbsp;better understand the range of&nbsp;legal solutions&nbsp;that&nbsp;exist and&nbsp;identify critical&nbsp;concepts and language for&nbsp;screening questions.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results</strong><strong>:&nbsp;</strong>The study team developed a&nbsp;brief survey&nbsp;that can be used in clinic&nbsp;to screen individual adolescents for potential, actionable&nbsp;legal needs. Some questions were adapted from existing resources, while others were newly synthesized.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><strong>&nbsp;</strong>The screening tool&nbsp;will&nbsp;be piloted with a&nbsp;representative sample of&nbsp;at-risk&nbsp;youth&nbsp;and eventually&nbsp;implemented&nbsp;in adolescent-focused&nbsp;FQHC&nbsp;sites&nbsp;with&nbsp;active&nbsp;MLPs.&nbsp;This&nbsp;tool&nbsp;will&nbsp;be used to identify actionable legal needs and prompt&nbsp;referrals to legal professionals who can&nbsp;help adolescents&nbsp;resolve&nbsp;health-harming legal needs&nbsp;that may&nbsp;prevent access&nbsp;to the HIV&nbsp;CoC.</p> 2018-12-07T14:13:27-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22763 Paradoxical rapid normalization of serum proteins in severely sarcopenic pediatric patients following liver transplant 2019-01-08T13:21:51-05:00 Christian M. Schmidt II imprs@iupui.edu Richard S. Mangus imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Pediatric&nbsp;liver disease&nbsp;patients develop frailty&nbsp;which risks&nbsp;adverse outcomes.&nbsp;This&nbsp;novel&nbsp;study&nbsp;aims to quantify differential rates of sarcopenia&nbsp;in&nbsp;pediatric liver failure&nbsp;pre/post-transplant&nbsp;as a function of&nbsp;nutritional parameters and dynamic changes in&nbsp;muscle mass.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Project Methods:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>A retrospective review of a prospectively collected transplant database (2001-2018) at a single center was performed.&nbsp;Weekly&nbsp;serum protein&nbsp;values&nbsp;(albumin and total protein)&nbsp;and&nbsp;monthly&nbsp;body weights (BWs) and&nbsp;BMIs&nbsp;were collected.&nbsp;A select&nbsp;group&nbsp;with&nbsp;CT&nbsp;imaging pre/post-transplant&nbsp;underwent&nbsp;scaled scoring&nbsp;(cross sectional area at L2/L3 intervertebral space&nbsp;divided&nbsp;by height<span data-fontsize="11">2&nbsp;</span>for&nbsp;core muscle mass).&nbsp;The post-transplant rates of change were compared to pre-transplant&nbsp;baseline nutrition status.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>There were 114&nbsp;subjects,&nbsp;82&nbsp;underwent&nbsp;CT&nbsp;analysis.&nbsp;Pre-transplant,&nbsp;45%&nbsp;had severe sarcopenia.&nbsp;Post-transplant, median&nbsp;serum protein&nbsp;levels normalized, but&nbsp;slowest&nbsp;in patients&nbsp;infants.&nbsp;BMI and&nbsp;BW&nbsp;were unchanged&nbsp;except in&nbsp;adolescents&nbsp;it&nbsp;significantly&nbsp;decreased in the first 30 days.&nbsp;Paradoxically, median serum protein&nbsp;levels normalized at week 3 for&nbsp;patients&nbsp;with&nbsp;severe sarcopenia,&nbsp;faster than mild/moderate sarcopenia groups.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><span data-ccp-props="{&quot;134233279&quot;:true,&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Liver transplant normalizes&nbsp;serum proteins&nbsp;at differential rates according to age, pre-transplant BMI and level of sarcopenia. Despite&nbsp;normalization liver transplant does not change&nbsp;BW&nbsp;and BMI.&nbsp;&nbsp;Paradoxically,&nbsp;severe sarcopenia patients normalize their serum&nbsp;protein&nbsp;levels&nbsp;at the fastest rate.&nbsp;We&nbsp;speculate an increased level of a novel “protein-stimulating factor” may exist&nbsp;in the&nbsp;severely sarcopenic&nbsp;group.&nbsp;Understanding post-liver transplant outcomes in patients as a function of their pre-transplant sarcopenic&nbsp;index is&nbsp;a novel method to optimize&nbsp;these patients care.&nbsp;</p> 2018-12-07T14:14:02-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22764 Determining Health Utilities for Immunosuppression in Pediatric Inflammatory Bowel Disease 2019-01-08T13:21:51-05:00 Lauren Schmidt, BA imprs@iupui.edu William E. Bennett, Jr., MD, MS imprs@iupui.edu <p><strong>Background and Hypothesis:</strong>&nbsp;Inflammatory Bowel Disease is a significant cause of gastrointestinal pathology in children and adolescents, with increasing incidence.<span data-fontsize="11">&nbsp;</span>The medications used to control this disease have an overall low risk of detrimental side effects, but when they occur can be serious or life-threatening. The most important side effects of immunosuppression in IBD are infection and malignancy, but little is known about how these risks affect patients’ and their families’ decisions about medication use.&nbsp; Clinical utilities are a standard methodology used to assign risk to various hypothetical health states. We hypothesized that lower health utility scores would be assigned to scenarios related to cancer than to infection, even if the risks or severity were similar.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods:</strong>&nbsp;This study determines the clinical utility of immunosuppression and cancer / infection risk in children with inflammatory bowel disease using the standard gamble technique.&nbsp; The standard gamble technique measures individual preferences for many different therapeutic modalities, under uncertain results. The study will look at the health utilities of at least 50 families at Riley hospital for Children and IU North, with at least 25 patients with ulcerative colitis and 25 patients with Crohn’s disease. In addition to the perfect health and death, we propose to utilize six different hypothetical health states during this study: (1) untreated IBD, (2) on a medication with no side effects, (3) on a medication with risk of a treatable infection, (4) on a medication with risk of an untreatable infection, (5) on a medication with risk of a treatable cancer, (6) and on a medication with risk of an untreatable cancer. We will also gather subject demographics, family education, family income, and perform an assessment of numeracy. These variables will then be used in a regression model to assess the effect of these confounders.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:&nbsp;</strong>We have not yet enrolled subjects, but now that the tool and Standard Gamble design are complete, we expect to rapidly accrue enrollment over the next two weeks and will update results at that time.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong>&nbsp;Health utility data in pediatric IBD are quite scarce, with room for further research. It is crucial to understand the health utilities in individuals with inflammatory bowel disease (IBD), specifically in pediatric patients. This allows for cost-utility analysis to play a role in determining effectiveness for a wide variety of treatment modalities. It is also important when discussing treatment options with families when the risk of infection or cancer are present.&nbsp; Knowledge gained from this study may help us design interventions that focus on educating families about the nature and magnitude of these important risks in immunosuppressive therapy.&nbsp;</p> 2018-12-07T14:14:57-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22765 Transjugular Intrahepatic Portosystemic Shunt (TIPS) Creation to Improve Surgical Candidacy Prior to Abdominal Operation: A Retrospective Analysis 2019-01-08T13:21:50-05:00 Adam Schmitz imprs@iupui.edu Paul Haste, MD imprs@iupui.edu Matthew S. Johnson, MD imprs@iupui.edu <p><strong>Background and Hypothesis:</strong>&nbsp;TIPS creation is typically reserved for patients with refractory ascites or variceal hemorrhage. While TIPS&nbsp;have&nbsp;also been&nbsp;created&nbsp;prior to planned abdominal operation to decrease morbidity related to portal hypertension, there is little in the literature supporting its efficacy in that indication. The goal of this study was to determine if preoperative TIPS creation allows successful abdominal operation and improves outcomes.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods:</strong>&nbsp;A retrospective review of records of&nbsp;22 patients who underwent preoperative TIPS&nbsp;creation between 2011 and 2016 was performed.&nbsp;Clinical and serologic data were&nbsp;obtained for&nbsp;21 patients since&nbsp;one&nbsp;patient&nbsp;was&nbsp;completely lost to follow up&nbsp;after TIPS creation. The&nbsp;primary endpoint was whether&nbsp;patients&nbsp;underwent planned abdominal operation following TIPS. Operative outcomes and reasons that patients failed to undergo planned operation were examined as secondary endpoints.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Results:</strong>&nbsp;The mean age was 56.4 ± 8.8&nbsp;years, and the mean Child-Pugh and Model for End-Stage Liver Disease (MELD) scores were 7.2 ± 1.5 and 11.9&nbsp;± 4.3, respectively. Thirty-day mortality after TIPS creation was 9.5%. Eleven patients (52.4%) underwent planned abdominal operation and the thirty-day mortality rate was 0%. One of these 11 patients (9.1%) had&nbsp;surgical wound dehiscence and infection 53 days after operation. Reasons for failure to proceed to abdominal operation after TIPS were multifactorial.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:&nbsp;</strong>In our population, TIPS allowed successful abdominal operation in the majority of patients, with thirty-day TIPS mortality of 9.5%, no&nbsp;perioperative mortality, and 9.1%&nbsp;major postoperative morbidity.</p> 2018-12-07T14:15:35-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22766 The Association of Haptoglobin Genotype with the Development of Liver Disease and a Strategy for Personalized Treatment of NASH 2019-01-08T13:21:50-05:00 Nicole Shammas imprs@iupui.edu Tiebing Liang, PhD imprs@iupui.edu <p><em>Background</em>&nbsp;Haptoglobin is a binding protein that scavenges free hemoglobin and is highly expressed in the liver. The human haptoglobin gene (<em>HP</em>) is polymorphic, consisting of two alleles,&nbsp;<em>HP1</em>&nbsp;and&nbsp;<em>HP2</em>. Recent studies have found that haptoglobin variants are strongly associated with cholesterol levels, as haptoglobin is capable of binding apolipoprotein E and regulating HDL function<span data-fontsize="11">3-4</span>. Together, these functions allow haptoglobin to play a significant role in the transport of cholesterol from tissues to the liver.&nbsp;<em>Goal</em>&nbsp;Study the association of haptoglobin genotypes with the development of nonalcoholic steatohepatitis (NASH) using 2000 NASH CRN patient DNA samples.&nbsp;<em>Methods</em>&nbsp;Allelic differences were determined using TaqMan genotyping PCR and were analyzed on an ABI7300 real-time PCR machine. Following allele identification, the association between genotype and phenotype was determined, with focus on NASH scores and other relevant measurements.&nbsp;<em>Results</em>&nbsp;The distribution of haptoglobin genotype frequencies were 46%&nbsp;<em>HP1/HP2</em>, 39%&nbsp;<em>HP2/HP2</em>, and 15%&nbsp;<em>HP1/HP1</em>, with no gender differences. The results suggest that&nbsp;<em>HP2/HP2&nbsp;</em>is associated with specific liver disease states such as an NAFLD score of 6, fibrosis&nbsp;in zone 2 of the liver and periportal area, and a steatosis&nbsp;grade of 34-66%. The most abundant genotype observed was&nbsp;heterozygous for several ethnic groups, as expected. However, patients of Asian ancestry demonstrated homozygous&nbsp;<em>HP2</em>&nbsp;as the majority genotype.&nbsp;<em>Conclusion</em>&nbsp;HP genotype plays an important role in liver disease development. Genotyping distribution differences in ethnic groups may inform personalized treatment strategies, such as recommending Vitamin E for patients homozygous for&nbsp;<em>HP2</em><span data-fontsize="11">1</span>&nbsp;<span data-fontsize="11">2</span>.&nbsp;<span data-ccp-props="{}">&nbsp;</span></p> <p>1.Zang, S.; Chen, J.; Song, Y.; Bai, L.; Chen, J.; Chi, X.; He, F.; Sheng, H.; Wang, J.; Xie, S.; Xie, W.; Yang, Y.; Zhang, J.; Zheng, M.; Zou, Z.; Wang, B.; Shi, J.; Chinese, N. C. R. N., Haptoglobin Genotype and Vitamin E Versus Placebo for the Treatment of Nondiabetic Patients with Nonalcoholic Steatohepatitis in China: A Multicenter, Randomized, Placebo-Controlled Trial Design.&nbsp;<em>Adv Ther&nbsp;</em><strong>2018,</strong>&nbsp;<em>35</em>&nbsp;(2), 218-231.<span data-ccp-props="{}">&nbsp;</span></p> <p>2.Boettger, L. M.; Salem, R. M.; Handsaker, R. E.; Peloso, G. M.; Kathiresan, S.; Hirschhorn, J. N.; McCarroll, S. A., Recurring exon deletions in the HP (haptoglobin) gene contribute to lower blood cholesterol levels.&nbsp;<em>Nat Genet&nbsp;</em><strong>2016,</strong>&nbsp;<em>48</em>&nbsp;(4), 359-66.<span data-ccp-props="{}">&nbsp;</span></p> <p>3.Spagnuolo, M. S.; Maresca, B.; La Marca, V.; Carrizzo, A.; Veronesi, C.; Cupidi, C.; Piccoli, T.; Maletta, R. G.; Bruni, A. C.; Abrescia, P.; Cigliano, L.,&nbsp;Haptoglobin interacts with apolipoprotein E and beta-amyloid and influences their crosstalk.&nbsp;<em>ACS Chem Neurosci&nbsp;</em><strong>2014,</strong>&nbsp;<em>5</em>&nbsp;(9), 837-47.<span data-ccp-props="{}">&nbsp;</span></p> <p>4.Costacou, T.; Levy, A. P.; Miller, R. G.; Snell-Bergeon, J.; Asleh, R.; Farbstein, D.; Fickley, C. E.; Pambianco, G.; de la Vega, R.; Evans, R. W.; Orchard, T. J., Effect of vitamin E supplementation on HDL function by haptoglobin genotype in type 1 diabetes: results from the HapE randomized crossover pilot trial.&nbsp;<em>Acta Diabetol&nbsp;</em><strong>2016,</strong>&nbsp;<em>53</em>&nbsp;(2), 243-50.<span data-ccp-props="{}">&nbsp;</span></p> 2018-12-07T14:16:11-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22767 Effect of Tyrosine Phosphorylation of HPV31 E2 on Replication 2019-01-08T13:21:50-05:00 Mitra Sharifi imprs@iupui.edu Timra Gilsonq imprs@iupui.edu Elliot Androphy imprs@iupui.edu <p><strong>Background</strong><span data-ccp-props="{&quot;335559740&quot;:360}">&nbsp;</span></p> <p>The HPV early E2 protein is an essential regulatory protein involved in HPV replication and transcription that is encoded by all papillomaviruses. Phosphorylation of E2 at Y102 inhibits viral replication, and an additional phosphorylation site at Y87 was recently identified through mass spectrometry. This project aimed to characterize E2 proteins encoding mutations at Y87 that abrogate phosphorylation. In parallel, we aimed to identify the kinase responsible for E2 phosphorylation at Y87. The&nbsp;Androphy&nbsp;lab previously has published that FGFR tyrosine kinases effect HPV replication, but there may be other kinases which act upon E2. Tyk2 is a tyrosine kinase regulated by the viral protein E6 and highly expressed in keratinocytes. We want to determine if Tyk2 is involved in regulation of E2 through phosphorylation.<span data-ccp-props="{&quot;335559740&quot;:360}">&nbsp;</span></p> <p><strong>Experimental Design</strong><span data-ccp-props="{&quot;335559740&quot;:360}">&nbsp;</span></p> <p>We will co-express Tyk2 and E2 in 293TT cells and through immunoprecipitations determine if Tyk2 binds E2. Using an in-vitro replication assay, viral proteins E2 and E1 will be overexpressed along with Tyk2 to determine if Tyk2 effects replication. We will make HPV genomes with Y87E/Y87F mutations through site-directed mutagenesis. Expression of mutant E2 will be examined through transfection of cells and western blot analysis.<span data-ccp-props="{&quot;335559740&quot;:360}">&nbsp;</span></p> <p><strong>Results</strong><span data-ccp-props="{&quot;335559740&quot;:360}">&nbsp;</span></p> <p>E2 harboring 87 to glutamic acid (Y87E) or phenylalanine (Y87F) mutations produces soluble protein,&nbsp;but 87E inhibits replication. Tyk2 expression stabilizes E2 suggesting it binds E2.<span data-ccp-props="{&quot;335559740&quot;:360}">&nbsp;</span></p> <p><strong>Potential impact</strong><span data-ccp-props="{&quot;335559740&quot;:360}">&nbsp;</span></p> <p>It is important to understanding the mechanisms underlying a virus’ replication cycle for future targeted treatments against infection.</p> 2018-12-07T14:17:00-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22768 Pneumonia in Indiana nursing homes: a retrospective case series 2019-01-08T13:21:50-05:00 Andrew Shearn imprs@iupui.edu Kathleen Unroe, MD, MHA imprs@iupui.edu Jennifer Carnahan, MD, MPH, MA imprs@iupui.edu <p><strong>Background</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>The&nbsp;Optimizing Patient Transfers, Impacting Medical Quality, &amp; Improving Symptoms: Transforming Institutional Care&nbsp;(OPTIMISTIC) project is&nbsp;a&nbsp;Centers for Medicare and Medicaid&nbsp;(CMS)&nbsp;demonstration project,&nbsp;tasked with reducing&nbsp;potentially&nbsp;avoidable hospitalizations of nursing home residents.&nbsp;OPTIMISTIC-enrolled nursing homes are&nbsp;reimbursed by CMS for treating residents with pneumonia in place.&nbsp;The purpose of this study is to examine the diagnosis, treatment, and outcomes of episodes of pneumonia in OPTIMISTIC nursing homes.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Project Methods</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>This case series uses data&nbsp;from&nbsp;nursing home&nbsp;medical&nbsp;records of the seven&nbsp;facilities with the highest&nbsp;pneumonia&nbsp;caseload&nbsp;identified&nbsp;from the OPTIMISTIC database. Cases are from&nbsp;billing episodes spanning&nbsp;November 2017 through&nbsp;April&nbsp;2018. Within each facility,&nbsp;cases of pneumonia were randomly selected for inclusion. Data were entered into&nbsp;an&nbsp;extraction tool designed by the study team.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Data were extracted from&nbsp;41&nbsp;records of unique patients.&nbsp;Despite&nbsp;CMS&nbsp;reimbursing&nbsp;for a maximum of 7 days for&nbsp;treatment&nbsp;of pneumonia,&nbsp;78.0% of patients were monitored beyond that time and&nbsp;with greater attention&nbsp;than usual care.&nbsp;Of&nbsp;all 41 patients treated with&nbsp;antibiotics,&nbsp;53.7% were given a fluoroquinolone and 24.4%&nbsp;were given&nbsp;amoxicillin/clavulanate.&nbsp;&nbsp;CURB-65&nbsp;scores&nbsp;showed&nbsp;58.3%&nbsp;scored&nbsp;in a range&nbsp;recommending hospitalization.&nbsp;Most&nbsp;patients&nbsp;(87.8%)&nbsp;were stabilized in the nursing home; three&nbsp;(7.3%)&nbsp;were hospitalized,&nbsp;one&nbsp;(2.4%) transferred to hospice, and&nbsp;one&nbsp;(2.4%) died.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and&nbsp;</strong><strong>Potential Impact</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>OPTIMISTIC-affiliated nursing facilities&nbsp;successfully&nbsp;provide&nbsp;enhanced&nbsp;care for most patients diagnosed with pneumonia in the facilities.&nbsp;Given&nbsp;the&nbsp;high incidence of fluoroquinolone use, one area for improvement is&nbsp;reduction of this medication contraindicated&nbsp;in&nbsp;the elderly.</p> 2018-12-07T14:17:49-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22771 Copy Number Analysis of Lung Tumor Progression in Mice 2019-01-08T13:21:49-05:00 Paige A. Schultheis imprs@iupui.edu Elizabeth A. Mickler imprs@iupui.edu Robert S. Stearman imprs@iupui.edu Mark W. Geraci imprs@iupui.edu <p><strong>Background &amp; Hypothesis</strong><span data-ccp-props="{}">&nbsp;</span></p> <p>The&nbsp;xeroderma&nbsp;pigmentosum&nbsp;group C (XPC) gene encodes a protein that repairs DNA damage, like that caused by UV light. Its mutation in patients is associated with increased risk of melanoma. In our mouse model, the&nbsp;Xpc&nbsp;gene has a targeted deletion, leading to increased frequency of lung tumors in a mouse strain typically resistant to lung chemical carcinogenesis. We hypothesize that there will be enrichment of specific copy number variations (CNVs) in the genome throughout tumor progression that can distinguish the different stages of carcinogenesis in lung cancer.<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Project Methods</strong><span data-ccp-props="{}">&nbsp;</span></p> <p>Urethane treatments induced lung tumors in&nbsp;Xpc&nbsp;-/- (ko) mice. Laser capture microscopy was used to isolate tumor, hyperplasia, and normal tissue from lung sections.&nbsp;After DNA extraction, genomic&nbsp;DNA&nbsp;(gDNA)&nbsp;was quantified using&nbsp;Quantifluor&nbsp;assay. Whole genome amplification was completed using&nbsp;Repli-G&nbsp;kit. PCR,&nbsp;copy number analysis, and&nbsp;restriction enzyme digestion were quality control measures for&nbsp;amplified&nbsp;gDNA.&nbsp;Single nucleotide polymorphism (SNP) microarrays will assess CNVs in samples that are successfully amplified.<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Results</strong><span data-ccp-props="{}">&nbsp;</span></p> <p>DNA was successfully amplified, as confirmed by the&nbsp;Quantifluor&nbsp;assay.&nbsp;PCR, copy number analysis, and restriction enzyme digestion confirmed&nbsp;3 out of the 4 amplified samples were&nbsp;comparable&nbsp;to matched non-amplified samples, suggesting mouse&nbsp;gDNA&nbsp;was maintained.&nbsp;<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Potential Impact</strong><span data-ccp-props="{}">&nbsp;</span></p> <p>The mouse model findings can be applied to publically available human genome databases of lung cancer CNVs. Overlapping findings in mice and human CNVs may give insight into novel pathways for effective treatment in lung cancer.&nbsp;<span data-ccp-props="{}">&nbsp;</span></p> 2018-12-07T14:18:26-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22772 Predictors of Patient Function, Pain, and Satisfaction after Reimplantation for Infected Hip and Knee Arthroplasty 2019-01-08T13:21:49-05:00 Christian Sikoski imprs@iupui.edu Mary Ziemba-Davis, BA imprs@iupui.edu R. Michael Meneghini, MD imprs@iupui.edu <p><strong>Background</strong><strong>/</strong><strong>Hypothesis:</strong>&nbsp;Prevalence of periprosthetic joint infection (PJI) is expected to rise as hip and knee arthroplasty procedures increase.&nbsp;This study purpose was to evaluate factors affecting&nbsp;patient-reported outcomes&nbsp;after resection and reimplantation procedures.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Project Methods:</strong><strong>&nbsp;</strong>38 hips&nbsp;and 35 knees&nbsp;consecutively&nbsp;treated&nbsp;by a single surgeon&nbsp;were retrospectively reviewed.&nbsp;Prospectively collected preoperative and minimum one and two-year&nbsp;postoperative&nbsp;Knee Injury and Osteoarthritis Outcome Score/KOOS Jr., Hip Disability and Osteoarthritis Outcome Score/HOOS Jr., UCLA&nbsp;Activity&nbsp;Level, and satisfaction were compiled.&nbsp;Fifteen demographic variables and covariates of outcomes&nbsp;(sex, age, etc.)&nbsp;were accounted for in analysis.&nbsp;&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><strong>&nbsp;</strong>47%&nbsp;of hip and&nbsp;71% of knee patients&nbsp;were chronically infected&nbsp;poor hosts (McPherson&nbsp;stage III-B/C).&nbsp;In hips,&nbsp;worse McPherson&nbsp;stage&nbsp;was&nbsp;associated with lower&nbsp;activity levels&nbsp;at&nbsp;latest follow-up&nbsp;(<em>p</em>=0.007).&nbsp;Activity&nbsp;was&nbsp;higher in hip patients with constrained liners&nbsp;compared to&nbsp;dual mobility implants&nbsp;at one (<em>p</em>=0.009) and two-year (<em>p</em>=0.001)&nbsp;follow-up.&nbsp;The same result was observed in knees&nbsp;with&nbsp;varus-valgus constrained liners vs. hinged implants&nbsp;(p=0.005,&nbsp;p=0.029).&nbsp;However,&nbsp;varus-valgus constrained articulations&nbsp;were associated with&nbsp;more stair pain at&nbsp;one (p=0.003) and two (p=0.012)&nbsp;years.&nbsp;83% of hip and knee patients&nbsp;were satisfied or very satisfied with their outcome at&nbsp;latest&nbsp;follow-up.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion</strong><strong>/</strong><strong>Potential Impact:</strong><strong>&nbsp;</strong>Positive outcomes observed&nbsp;following reimplantation procedures&nbsp;will help establish patient expectations.&nbsp;&nbsp;It appears the increased joint stability imparted by hinged TKA and constrained&nbsp;liners in THA may offer advantage in stair pain and clinical function, respectively, in reimplantation arthroplasty after PJI.&nbsp;&nbsp;</p> 2018-12-07T14:19:01-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22773 Modulation of Myocardial Oxygen Delivery in Response to Isovolemic Hemodilution 2019-01-08T13:21:49-05:00 Blake R. Simon imprs@iupui.edu Hana E. Baker imprs@iupui.edu Conner C. Earl imprs@iupui.edu Adam G. Goodwill imprs@iupui.edu Sam Luebbe imprs@iupui.edu Johnathan D. Tune imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><strong>&nbsp;</strong>Prior studies have established that progressive increases in coronary blood flow are sufficient to maintain myocardial oxygen delivery in&nbsp;response to reductions in arterial oxygenation. However, the precise mechanisms responsible&nbsp;for anemic coronary vasodilation remain poorly understood. This investigation tested&nbsp;the hypothesis that autonomic neural pathways contribute to the maintenance of myocardial oxygen delivery in response to&nbsp;graded&nbsp;reductions in&nbsp;arterial hematocrit.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design:</strong><strong>&nbsp;</strong>Experiments were conducted in open-chest anesthetized swine while assessing coronary blood flow and coronary arterial and venous blood gases in response to progressive hemodilution. Isovolemic hemodilution was achieved via&nbsp;simultaneous removal of 250mL of arterial blood and addition of 250mL of&nbsp;a&nbsp;synthetic plasma expander&nbsp;(Hespan)&nbsp;in swine that received either vehicle or a combination of atropine&nbsp;(0.5mg/kg)&nbsp;and propranolol&nbsp;(1mg/kg)&nbsp;(Atro/Pro).<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong>&nbsp;Relative to vehicle control swine, treatment with&nbsp;Atro/Pro&nbsp;increased heart rate by ~50±4 beats/min and arterial pressure by ~10±1 mmHg.&nbsp; However,&nbsp;Atro/Pro did not significantly alter increases in&nbsp;coronary blood flow&nbsp;in response to isovolemic hemodilution (hematocrits ranging from ~35±1% to ~15±1%). Coronary venous PO<span data-fontsize="11">2</span>, an index of myocardial oxygenation, was also unchanged by hemodilution in both vehicle and&nbsp;Atro/Pro treated swine.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><strong>&nbsp;</strong>These data suggest that autonomic neural pathways do not play a significant role in&nbsp;the maintenance of myocardial oxygen delivery&nbsp;in&nbsp;response to graded reduction in arterial oxygen content.&nbsp;Understanding of how myocardial oxygen supply is ultimately sensed and regulated in response to reductions in tissue oxygenation remains elusive.&nbsp;&nbsp;</p> 2018-12-07T14:19:35-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22774 Enhancing cytotoxic chemotherapy response through targeted BET bromodomain inhibition in preclinical pancreatic cancer models 2019-01-08T13:21:49-05:00 Sandeep Singh imprs@iupui.edu Ross McCauley imprs@iupui.edu Johann R. Schwarz imprs@iupui.edu Roderich Schwarz imprs@iupui.edu Niranjan Awasthi imprs@iupui.edu <p><strong>Background and Hypothesis</strong><strong>:&nbsp;</strong><span data-ccp-props="{}">&nbsp;</span></p> <p>Pancreatic ductal adenocarcinoma (PDAC)&nbsp;has a poor prognosis and the standard of care regimen, nab-paclitaxel (NPT) plus gemcitabine (Gem), leads to a dismal 8.5 months median survival.&nbsp;Targeted inhibition of&nbsp;Bromodomain&nbsp;and Extra-Terminal (BET) protein is currently under investigation for several cancers. We hypothesize that BET protein pathway inhibition&nbsp;by iBet-762&nbsp;will enhance cytotoxic chemotherapy response in&nbsp;PDAC.<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Experimental Design</strong><strong>:</strong><span data-ccp-props="{}">&nbsp;</span></p> <p><em>In vitro</em>&nbsp;cell proliferation assays&nbsp;were performed using&nbsp;WST-1 reagent. Protein&nbsp;expressions were determined by Western Blot analysis.&nbsp;<em>In vivo</em>&nbsp;animal survival and tumor growth experiments were performed in NOD-SCID mice.&nbsp;<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Results</strong><strong>:</strong><span data-ccp-props="{}">&nbsp;</span></p> <p>Inhibition in cell proliferation in human&nbsp;PDAC cells&nbsp;at 1 µM concentration in&nbsp;NPT+Gem, iBET-762,&nbsp;and NPT+Gem+iBet762 was 64%, 27%, 76% in AsPC-1; 43%, 13%, 69% in Panc-1; and 42%, 51%,&nbsp;75% in MIA&nbsp;PaCa&nbsp;cells.&nbsp;iBET-762 decreased oncogenic proteins&nbsp;c-Myc,&nbsp;[Symbol]-catenin, Vimentin, and P-AKT while apoptosis related proteins such as cleaved PARP-1&nbsp;and&nbsp;cleaved caspase-3 and cell cycle inhibitors proteins P21 &amp; P27 were increased. In a peritoneal dissemination model, median animal survival compared to control (21 days) was increased after therapy with&nbsp;NPT+Gem&nbsp;(33 days, a 57% increase),&nbsp;iBet-762&nbsp;(30 days, a 43% increase)&nbsp;and NPT+Gem+iBET-762 (44 days, a 110% increase). Effect of iBET-762&nbsp;in combination with chemotherapy on local tumor growth is currently underway.&nbsp;&nbsp;<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><strong>&nbsp;</strong><span data-ccp-props="{}">&nbsp;</span></p> <p>These findings suggest that the effects of standard chemotherapy can be enhanced through specific inhibition of BET proteins activity, and supports the clinical application of iBET-762 in combination with standard chemotherapy in PDAC patients.</p> 2018-12-07T14:20:12-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22775 A Descriptive Time Inventory of Emergency Department Nursing Workflows 2019-01-08T13:21:49-05:00 Dana Skold imprs@iupui.edu Alice Mitchell, MD imprs@iupui.edu <p><strong>Background:&nbsp;</strong>Previous emergency department (ED) process improvement efforts&nbsp;used probabilistic analytical or simulated models without considering the impact of specific tasks on ED patient flow and resource needs. We focus on the tasks and workflows that comprise nursing activity in an&nbsp;urban academic ED and level I trauma center receiving over 80,000 annual visits.<span data-ccp-props="{&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design:&nbsp;</strong>Using a time/motion observational methodology, we create a minute-by-minute time inventory account of nursing tasks and workflows as observed through the activities of 35 nurses over 124.5 hours, representative of 24/7 patient care in 7 ED care areas.&nbsp;“Tasks”&nbsp;were defined as discrete, measurable, and consequential step(s) to accomplish a clinically meaningful goal&nbsp;(“workflow”).&nbsp;The task with highest cognitive demand for each minute of observation was recorded.&nbsp;We also tracked 12 discrete highest-acuity (“shock”) events and catalogued second-by-second observational accounts of each nurse diverted.&nbsp;<span data-ccp-props="{&quot;335551550&quot;:1,&quot;335551620&quot;:1,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:&nbsp;</strong>Our data&nbsp;demonstrate&nbsp;significant variation in&nbsp;tasks&nbsp;based on time of day.&nbsp;We observed substantial operational load moving patients between care areas, with intake and discharge comprising 25% of nurse workflows. Downtime averaged 32%, with variation depending on care area. Downtime was highest (47%) with passive video monitoring of psychiatric care and lowest (22%) in high-turnover intake areas. Highest-acuity patient-care events result in significant and variable nurse diversion from other tasks averaging 1:03:29 in combined nursing effort.<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><strong>&nbsp;</strong>Movement of patients between care areas represents significant operational load. Interruptions and task preparation accounted for a surprising portion of activity.&nbsp; Highest-acuity patient care events result in substantial and variable diversion of nurse care.&nbsp;</p> 2018-12-07T14:20:46-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22791 Chamas for Change: A Community Based Strategy for Pregnancy, Infancy, and Women Empowerment 2019-01-08T13:21:48-05:00 Ryan Smith imprs@iupui.edu Laura Ruhl imprs@iupui.edu <p><strong>Background</strong><strong>:</strong><strong>&nbsp;</strong>Maternal mortality is the leading cause of death among women of childbearing age in Kenya,&nbsp;and 1 in every 19 infants dies before their first birthday.<strong>&nbsp;</strong>To address this,&nbsp;Chama cha MamaToto&nbsp;was developed&nbsp;as a&nbsp;community-based&nbsp;program for pregnant and breast-feeding women. It integrates health and social education to decrease poor health outcomes and parental stress. It also uses a table banking system called GISHE to develop financial independence.&nbsp;Central to Chamas is peer support and accountability,&nbsp;leading&nbsp;to&nbsp;empowerment of the women. This poster&nbsp;is an analysis of the program’s history,&nbsp;and&nbsp;a&nbsp;summary of data collected by the MNCH team from MTRH.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><strong>&nbsp;</strong>Women in Chamas had 5 times the odds of delivering in a health facility (OR = 5.07, 95% CI: 2.74-9.39). Children in Chamas had 33% relative reduction in stunting. Women and children in Chamas experienced&nbsp;30% absolute reduction in harsh punishment (p&lt; 0.001) compared to the control group.&nbsp;The Chamas program showed the potential for combined relative reduction of stillbirths and infant deaths by 56 percent (p&lt;0.083).&nbsp;Additionally, women in Chamas had an 35% absolute increase in EBF for 6 months.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Personal role:</strong><strong>&nbsp;</strong>My role&nbsp;working with the Chamas program this summer involved a cost analysis of the program as well as developing an implementation manual.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion</strong><strong>:</strong><strong>&nbsp;</strong>The&nbsp;next steps for the program include a continued scale up in two new&nbsp;sub counties, validation of findings from a cluster RCT, and a scale up of the program to all of Kenya in 2019.</p> 2018-12-07T14:21:23-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22792 Senescent T cell population in Glioblastoma 2019-01-08T13:21:48-05:00 Leo Song imprs@iupui.edu Mario Henriquez imprs@iupui.edu Sreenivasulu Chintala, PhD imprs@iupui.edu Mahua Dey, MD imprs@iupui.edu <p><strong>Background and Hypothesis:</strong>&nbsp;Glioblastoma (GBM) is the most common primary brain tumor in adults and has a median overall survival of 20.6 months. Intracranial location, infiltrative growth with near 100% recurrence and the blood brain barrier are challenges which make treating GBM difficult. CD8<span data-fontsize="11">+</span>&nbsp;T cells (CTLs) are largely responsible for mediating anti-tumor responses and thus, are an endpoint to most immunotherapies. However, the immunosuppressive tumor microenvironment (TME) hampers T cell effectiveness and causes exhaustion and senescence. Senescent CTLs (CD28<span data-fontsize="11">-</span>CD57<span data-fontsize="11">+</span>)<span data-fontsize="11">&nbsp;</span>can result from DNA damage which causes loss of CD28. Lack of CD28 renders CTLs insensitive to immune signals and result in loss of cytotoxic functions.&nbsp;Thus, we hypothesize that CTLs have lost CD28 expression and are becoming senescent in the TME of GBM patients.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods:</strong>&nbsp;CD8 and CD28 RNA expression data was pulled from TCGA in glioma and normal brain patients and a Pearson’s correlation was conducted.&nbsp;Lymphocytes were isolated from patient tumor brain and blood and using flow cytometry, CD3+ CD8+ T cells were identified and stained for CD28, CD57, PD-1, and TIM-3.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Results:</strong><strong>&nbsp;</strong>RNA sequencing&nbsp;data from TCGA&nbsp;database on CD8 and CD28 expression showed a negative correlation in GBM patients compared to normal patients.&nbsp;Majority of&nbsp;CD8+ lymphocytes&nbsp;from&nbsp;patient&nbsp;brain had lost CD28+ expression&nbsp;compared to blood.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><strong>&nbsp;</strong>The increased senescent T cell population in GBM suggests that the TME has a mechanism for cytotoxic T cell immunosuppression. Preventing CD8+ T cell senescence in GBM can improve current immunotherapies by promoting activation of tumor infiltrating lymphocytes.</p> 2018-12-07T14:22:07-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22793 Investigating the role of COQ8B in aortic smooth muscle cells. 2019-01-08T13:21:48-05:00 Henry Stadler imprs@iupui.edu Stephanie Ware imprs@iupui.edu Benjamin Landis imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><span data-ccp-props="{}">&nbsp;</span></p> <p>Thoracic aortic aneurysm (TAA) is an&nbsp;aortopathy&nbsp;characterized by&nbsp;aortic&nbsp;enlargement and life-threatening complications such as aortic dissection and sudden cardiac death.&nbsp;Previous studies&nbsp;identified&nbsp;<em>COQ8B&nbsp;</em>as a candidate genetic modifier of TAA severity.&nbsp;<em>COQ8B</em>&nbsp;is important for mitochondrial biosynthesis of coenzyme Q, but its precise functions are not defined.&nbsp;We hypothesize that&nbsp;alteration of&nbsp;<em>COQ8B</em>&nbsp;influences&nbsp;TAA&nbsp;pathogenesis via&nbsp;energy and oxidant metabolism pathways.<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Experimental Design:</strong><span data-ccp-props="{}">&nbsp;</span></p> <p>Smooth muscle cells (SMCs)&nbsp;were&nbsp;cultured directly from&nbsp;leftover healthy aortic&nbsp;tissues&nbsp;acquired&nbsp;during cardiac transplant operations.&nbsp;At confluence of 50-70%, cells were transfected with siRNA targeting&nbsp;<em>COQ8B</em>&nbsp;or a non-targeting negative control siRNA. Gene expression was measured using real-time quantitative polymerase chain reaction (RT-qPCR).&nbsp; Production of the&nbsp;reactive oxygen species&nbsp;hydrogen peroxide (H<span data-fontsize="11">2</span>O<span data-fontsize="11">2</span>)&nbsp;was&nbsp;measured&nbsp;using the fluorescence-based&nbsp;Amplex&nbsp;Red Hydrogen Peroxide Assay (Invitrogen) in basal growth medium.&nbsp;<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Results:</strong><span data-ccp-props="{}">&nbsp;</span></p> <p>Expression of&nbsp;<em>COQ8B</em>&nbsp;decreased by approximately 75% to 85% at 48 hours following siRNA transfection compared with negative control.&nbsp; This was associated with approximately&nbsp;1.5 fold&nbsp;upregulation of the SMC contractile gene&nbsp;<em>CNN1</em>&nbsp;(p&lt;0.05).&nbsp; Knockdown of&nbsp;<em>COQ8B</em>&nbsp;did not appear to alter&nbsp;H<span data-fontsize="11">2</span>O<span data-fontsize="11">2</span>&nbsp;production measured at timepoints of 48 or 72 hours.&nbsp;<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Conclusion and Impact:</strong><span data-ccp-props="{}">&nbsp;</span></p> <p>Based on these preliminary data, decreased&nbsp;<em>COQ8B</em>&nbsp;expression appears to alter the contractile phenotype of SMCs but may not significantly influence extracellular levels of&nbsp;H<span data-fontsize="11">2</span>O<span data-fontsize="11">2</span>&nbsp;under basal conditions.&nbsp; Exogenous activation of pathways important for TAA pathogenesis may be required to elucidate the role of&nbsp;<em>COQ8B</em>. Ultimately, this work may lead to improved clinical approaches.&nbsp;</p> 2018-12-07T14:23:34-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22790 IL-6 Stimulates Autophagy in Wild Type and NRF2 Knock Out Mice β-cells 2019-01-08T13:21:48-05:00 K M Stucker imprs@iupui.edu M R Marasco imprs@iupui.edu C M Conteh imprs@iupui.edu C Muralidharan imprs@iupui.edu A K Linnemann imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:200,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Pancreatic β-cells exhibit high levels of metabolic activity which generates reactive oxygen species (ROS).  ROS&nbsp;can  lead&nbsp;to β-cell damage and death,&nbsp; which could contribute to diabetes development.&nbsp; Therefore, pathways reducing ROS are of interest as potential therapeutic targets.  We have demonstrated that IL-6 stimulates autophagy and protects&nbsp;β-cells from ROS and apoptosis.  IL-6 also stimulates the translocation of NRF2 to the mitochondria, which is accompanied by several markers of&nbsp;mitophagy, the&nbsp;autophagic&nbsp;degradation of mitochondria.  In this study, we ask where NRF2 fits in the pathway downstream of IL-6 by asking if NRF2 is required for IL-6 stimulation of autophagy and/or&nbsp;mitophagy.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:200,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:200,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Wild type and NRF2 knockout mice were intraperitoneally injected with saline or IL-6 for thirty minutes, and the&nbsp;pancreata&nbsp;were cryopreserved, and&nbsp;cryosectioned.  Immunofluorescence staining was carried out for LAMP-1 (a component of lysosomes) and&nbsp;LC3 (a component of&nbsp;autophagosomes).  Slides were imaged with a&nbsp;LSM 700 confocal microscope.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:200,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:200,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>IL-6 stimulated autophagy in wild type and NRF2 knockout mice, whereas saline injection did not.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:200,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:200,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>We have confirmed that IL-6 stimulates autophagy in pancreatic islets and shown that NRF2 is not required for this process.  Ongoing experiments are investigating if NRF2 is required for IL-6 stimulation of&nbsp;mitophagy. These results help us understand how NRF2 functions downstream of IL-6 in the protection of β-cells&nbsp;</p> 2018-12-07T14:24:19-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22794 Determining if Double Gene Knockdown of P65 and PDK2 Increases Cytotoxicity and Radiation Sensitivity of Pancreatic Cancer Cells 2019-01-08T13:21:47-05:00 Madison Tenbarge imprs@iupui.edu Devyn Townsend imprs@iupui.edu Ryan Erdwin imprs@iupui.edu Helen Chin-Sinex imprs@iupui.edu Marc Mendonca imprs@iupui.edu <p><strong>Background:</strong><strong>&nbsp;</strong>Pancreatic&nbsp;ductal adenocarcinoma (PDA)&nbsp;is currently the 4<span data-fontsize="11">th</span>&nbsp;leading cause of cancer&nbsp;death&nbsp;in the US&nbsp;because of&nbsp;late detection and&nbsp;resistance to chemotherapy and radiation.&nbsp;This&nbsp;tumor&nbsp;resistance&nbsp;is&nbsp;partially due to&nbsp;high activity of the transcription factor,&nbsp;NF-[Symbol]B&nbsp;which promotes&nbsp;cell&nbsp;survival and&nbsp;pyruvate dehydrogenase kinase 2 (PDK2)&nbsp;which regulates&nbsp;aerobic glycolysis&nbsp;(Warburg&nbsp;Metabolism),&nbsp;cell proliferation,&nbsp;and inhibition of apoptosis.&nbsp;We have&nbsp;shown&nbsp;that&nbsp;simultaneous treatment with the chemical&nbsp;NF-B inhibitor&nbsp;DMAPT&nbsp;and&nbsp;the Warburg inhibitor DCA is cytotoxic and enhances radiation-induced cell death in human PDA cells.&nbsp;&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design:</strong><strong>&nbsp;</strong>We hypothesize&nbsp;that double gene knockdown of the P65 subunit of NF-[Symbol]B and PDK2&nbsp;by siRNA&nbsp;will&nbsp;lead&nbsp;to increased cytotoxicity and radiation sensitivity. The&nbsp;PDA cell line (Mia PaCa-2) was&nbsp;utilized and&nbsp;was&nbsp;transfected with appropriate siRNAs. The cells were plated and followed by irradiation with either 0, 2, 4, or 6&nbsp;Gy&nbsp;of 160&nbsp;kVp&nbsp;X-rays.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><strong>&nbsp;</strong>Analysis of Western blots&nbsp;shows the successful silencing of P65, but&nbsp;the&nbsp;knockdown of PDK2&nbsp;are pending.&nbsp;The&nbsp;differences in&nbsp;plating efficiency&nbsp;were not found to be statistically significant between the treatment groups.&nbsp;The differences in survival fraction were not found to be statistically significant at 2, 4, or&nbsp;6&nbsp;Gy, but there is a trend for enhancement at 6&nbsp;Gy.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion</strong><strong>:</strong>&nbsp;Preliminary data&nbsp;indicate&nbsp;there was no increase in cytotoxicity&nbsp;or radiation-induced cell killing&nbsp;after&nbsp;treatment&nbsp;with&nbsp;SiP65, SiPDK2, or&nbsp;both.&nbsp;However, to date we have no evidence that siPDK2 is working and&nbsp;further experiments&nbsp;are underway.&nbsp;</p> 2018-12-07T14:24:53-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22795 Control of Chemotherapy-Induced Peripheral Neuropathy and HMGB1 Cytosolic Translocation in Dorsal Root Ganglion Sensory Neurons Using Olaparib 2019-01-08T13:21:47-05:00 Hannah Thielmeyer imprs@iupui.edu Jared Smith imprs@iupui.edu Fletcher White imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><strong>&nbsp;</strong>Oxaliplatin&nbsp;(OXL)-associated Chemotherapy-induced Peripheral Neuropathy (CIPN) is a frequent, potentially severe,&nbsp;and dose-limiting toxicity of colorectal cancer treatment. CIPN&nbsp;can persist for years beyond chemotherapy completion, causing significant challenges for cancer survivors due to its negative influence on quality of life.&nbsp;This work builds upon preliminary observations that platinum drugs lead to the release of a damage-associated protein, high mobility group box-1 (HMGB1). Drug-induced release of this protein from the nucleus into the cytosol and eventually into the extracellular compartment can sensitize primary afferent sensory neurons for prolonged periods of time,&nbsp;eliciting CIPN pain behavior in rodents. Inhibition of HMGB1 nuclear translocation&nbsp;through administration of&nbsp;olaparib&nbsp;may serve to diminish CIPN pain in a rodent model.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods:</strong><strong>&nbsp;</strong>Sprague-Dawley rats were given intraperitoneal injections of oxaliplatin and&nbsp;oliparib&nbsp;and measured using Von Frey Filaments for mechanical sensitivity and&nbsp;Plantar’s&nbsp;Test for thermal behavior. Lumbar dorsal root ganglions were collected for immunofluorescence to label tissues with anti-HMGB1 antibodies and analyzed.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><strong>&nbsp;</strong>Oliparib&nbsp;transiently reverses the OXL-induced tactile allodynia one hour after drug administration.&nbsp;Oliparib-treated rats also exhibit diminished cytosolic HMGB1, indicating a lack of nuclear translocation in medium and large diameter sensory neurons.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><strong>&nbsp;</strong>The reduced CIPN behavior after&nbsp;oliparib&nbsp;administration correlates with diminished cytosolic HMGB1. This identifies HMGB1 as an important co-regulator of neurotoxicity due to oxaliplatin, which may have important relevance for future techniques to reduce CIPN and increase efficacy of colorectal cancer treatment.&nbsp;</p> 2018-12-07T14:25:27-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22796  Early surgical intervention is indicated for recurrent spontaneous pneumothorax in children and adolescents 2019-01-08T13:21:47-05:00 Cody Tragesser imprs@iupui.edu Brian W. Gray, MD imprs@iupui.edu Matthew P. Landman, MD, MPH imprs@iupui.edu <p><strong>Background:</strong>&nbsp;Primary spontaneous pneumothorax (PSP) occurs most often in adolescent patients. There is consensus that surgical intervention plays an important role in preventing recurrence, however, the optimum timing of surgery is debated. We hypothesize that clinical and radiographic factors are associated with eventual need for surgery.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design:</strong>&nbsp;We searched the medical record for PSP patients between ages 9 and 21 treated from 1/1/08 to 12/31/17 and collected data on chest tube management, radiographic measurements, operative management, and recurrence. We performed&nbsp;univariate&nbsp;analysis on relationships between admission events and eventual surgery or other management strategies.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong>&nbsp;We identified 68 PSP admissions from 31 patients. Considering only first-time admissions, there was no association between eventual surgery and clinical factors and radiographic findings.&nbsp; The single factor associated with eventual surgery was history of pneumothorax in any lung (p=0.015). For patients with prior pneumothorax who underwent surgery, operation the day after admission would have reduced hospital stay by an average of 1.5 days (min=0, max=9) and an average of 2.2 days (min=0, max=10) if performed on the day of admission, with a mean 1.85 fewer chest x-rays (min=0, max=7). Considering only first admissions, ipsilateral recurrence rate was 16.7% after surgery, 46.7% after chest tube alone, and 100% after observation alone.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion:</strong>&nbsp;This analysis suggests that though eventual surgery is difficult to predict, ipsilateral recurrence rate is reduced following surgery. Furthermore, earlier operation in recurrent patients could reduce resource utilization. Thus, expedited surgical treatment may merit consideration in patients with a history of pneumothorax.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> 2018-12-07T14:25:57-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22797 SOX-2 Mediated Conversion of Astrocyte to Neuron 2019-01-08T13:21:47-05:00 Brady Tucker imprs@iupui.edu Wei Wu imprs@iupui.edu Xiao-Ming Xu imprs@iupui.edu <p><strong>Background</strong>:&nbsp;Axonal regeneration following SCI is crucial if individuals are to avoid permanent neurological damage.&nbsp;A plausible solution to circumvent neuronal death/ axonal degeneration may be in the conversion of ubiquitously distributed astrocytes into neurons. Previous research has shown that the neuronal transcription factor SOX-2 has the potential to convert mature glial cells into&nbsp;neuroblasts&nbsp;(iANBs). Furthermore,&nbsp;iANBs&nbsp;possess the capability to differentiate into functional neurons. Our study employs an&nbsp;<em>in vivo&nbsp;</em>mouse model to demonstrate the functional recovery that SOX-2 mediated conversion of astrocytes to neurons may pose following SCI.&nbsp;&nbsp;<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Methods</strong>: Our study utilized two populations of mice. The first population received thoracic T10 contusion injuries while the second population received cervical C5 dorsal hemi-sections. Mice were subsequently blindly categorized into groups A, B, and C (treatment groups) depending on which injection they would be receiving:&nbsp;LV-hNG2-GFP, LV-hNG2-SOX2, or LV-p75-2. Following injection, behavioral studies including Hargreaves, roto-rod, grid walk, BMS (contusion mice) and pellet retrieval (DH mice) were performed to assess functional recovery at 2 week intervals.<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Results</strong>:&nbsp;The astrocyte conversion to neuron project spans more than 16 weeks. Here we present data obtained in the first eight weeks which includes behavioral analyses of contusion injury mice. Currently grid walk, BMS, and Hargreaves testing show similar trends in spontaneous recovery however no significant difference is observed between the independent injection groups. On the contrary roto-rod analyses showed injection group C had a significantly lower latency to fall time in comparison to&nbsp;groups A&nbsp;and B six weeks post injection&nbsp;(wpi).<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Conclusion</strong>: The treatments are hypothesized to not take effect until approximately 8&nbsp;wpi&nbsp;thus we expect subsequent behavioral testing to reveal significant differences between treatment groups, ultimately taking one step closer towards therapeutic intervention following traumatic SCI.&nbsp;&nbsp;</p> 2018-12-07T14:26:41-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22798 Clinical and radiographic factors associated with appendectomy in pediatric patients with abdominal pain and equivocal imaging findings for appendicitis. 2019-01-08T13:21:47-05:00 Roziya Tursunova imprs@iupui.edu Matthew P. Landman, MD, MPH imprs@iupui.edu <p><strong>Background and Hypothesis</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335551550&quot;:6,&quot;335551620&quot;:6,&quot;335559739&quot;:200,&quot;335559740&quot;:276}">&nbsp;</span></p> <p>Acute appendicitis is&nbsp;a&nbsp;common&nbsp;surgical emergency&nbsp;in children. The diagnosis requires physicians to rely on clinical, radiographic and laboratory factors. The nonoperative management of appendicitis is becoming more frequent. This requires&nbsp;an accurate diagnosis prior to initiating therapy&nbsp;to prevent unnecessary antibiotic administration for abdominal pain unrelated to appendicitis.&nbsp;We hypothesize clinical and radiographic factors are associated with appendicitis in patients with abdominal pain and inconclusive imaging studies.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335551550&quot;:6,&quot;335551620&quot;:6,&quot;335559739&quot;:200,&quot;335559740&quot;:276}">&nbsp;</span></p> <p><strong>Methods</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335551550&quot;:6,&quot;335551620&quot;:6,&quot;335559739&quot;:200,&quot;335559740&quot;:276}">&nbsp;</span></p> <p>The DORIS (Dig Our RIS) interactive data-mining tool was utilized to identify patients&lt;18&nbsp;years of age presenting to the emergency department in 2016 with abdominal pain who obtained abdominal imaging suggestive of early acute appendicitis. Relevant clinical and radiographic information was obtained from the medical record for univariate analysis looking for associations&nbsp;with appendectomy.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335551550&quot;:6,&quot;335551620&quot;:6,&quot;335559739&quot;:200,&quot;335559740&quot;:276}">&nbsp;</span></p> <p><strong>Results</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335551550&quot;:6,&quot;335551620&quot;:6,&quot;335559739&quot;:200,&quot;335559740&quot;:276}">&nbsp;</span></p> <p>One hundred patients were identified with 21 excluded due to imaging for other reasons or with clear non-appendicitis etiologies for pain (e.g.&nbsp;trauma cases, ovarian cyst). Seventy-nine patients were included with 49 (62%)&nbsp;undergoing&nbsp;surgery and 30 who&nbsp;were observed and/or discharged&nbsp;from&nbsp;the&nbsp;ED. Important differences between surgical and nonsurgical patients included: white blood cell count (13.81±0.68 vs. 10.29±0.90, p=0.002), neutrophil percentage (78.31±1.90 vs. 67.78±2.65, p=0.002),&nbsp;appendiceal&nbsp;diameter on CT scan (9.37±0.53 vs. 7.58±0.30, p=0.013).&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335551550&quot;:6,&quot;335551620&quot;:6,&quot;335559739&quot;:200,&quot;335559740&quot;:276}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335551550&quot;:6,&quot;335551620&quot;:6,&quot;335559739&quot;:200,&quot;335559740&quot;:276}">&nbsp;</span></p> <p>In a&nbsp;group of patients with concern&nbsp;for appendicitis and imaging suggestive of early&nbsp;acute&nbsp;appendicitis, distinct clinical&nbsp;and radiographic&nbsp;characteristics are associated with&nbsp;appendicitis. Within a paradigm of nonoperative management of appendicitis, accurate diagnosis will prevent the overutilization of antibiotics.&nbsp;</p> 2018-12-07T14:27:54-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22799 Current Concepts in the Treatment of Patellofemoral Instability 2019-01-08T13:21:47-05:00 Gary Ulrich, BS imprs@iupui.edu Hemant Pandit, FRCS (Orth), DPhil (Oxon) imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Patellofemoral&nbsp;instability represents a disabling condition, which&nbsp;presents primarily in active, young patients with an increased incidence in the female sex.&nbsp;A&nbsp;patellar&nbsp;dislocation can occur from a high-energy trauma or&nbsp;from&nbsp;an atypical anatomy, such as&nbsp;trochlear dysplasia, patellar dysplasia, patella&nbsp;alta, increased&nbsp;tibial&nbsp;tuberosity-trochlear groove (TT-TG) distance, increased Q-angle, and ligamentous laxity.&nbsp;When&nbsp;a patient presents with patellofemoral instability, the orthopedic surgeon faces&nbsp;many decisions regarding the treatment.&nbsp;Since the risk of a second dislocation&nbsp;after an acute dislocation&nbsp;resides at approximately 17%, many orthopedic surgeons treat the first patellar dislocation&nbsp;non-operatively&nbsp;barring the patient lacks any atypical anatomy.&nbsp;However, after a second&nbsp;dislocation, the likelihood of recurrent&nbsp;dislocations increases to approximately&nbsp;50%, which directs most orthopedic surgeons&nbsp;to surgical treatment.&nbsp;The current work reviews the&nbsp;anatomical predispositions,&nbsp;clinical presentation,&nbsp;and treatment of patellofemoral instability.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>The&nbsp;review was constructed via an extensive literature search utilizing the databases of&nbsp;MEDLINE/PubMed,&nbsp;SportDiscus, CINAHL, and Cochrane Central Register of Controlled Trials.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Multiple treatments&nbsp;exist&nbsp;for patellofemoral&nbsp;instability, which include&nbsp;non-operative treatment, MPFL reconstruction,&nbsp;tibial&nbsp;tubercle osteotomy,&nbsp;and&nbsp;trochleoplasty, along with many other procedures. Each case requires a tailored approach&nbsp;to successfully treat the patellofemoral instability.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p>Patellofemoral&nbsp;instability represents a potentially debilitating condition of anterior knee pain and limited activity.&nbsp;Understanding the anatomical predispositions, clinical&nbsp;presentation, and treatment of patellofemoral instability marks the first step to&nbsp;caring for&nbsp;patients&nbsp;with this condition.</p> 2018-12-07T14:29:30-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22800 Molecular characteristics of serum hepatitis B virus (HBV) RNA: a novel biomarker for chronic HBV infection 2019-01-08T13:21:46-05:00 Juan D. Valdés, BS imprs@iupui.edu Zhanglian Xie, MD imprs@iupui.edu Haitao Guo, PhD imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><strong>&nbsp;</strong>HBV&nbsp;is&nbsp;a&nbsp;major etiological agent for viral hepatitis and hepatocellular carcinoma. HBV is a DNA virus per se but viral pregenomic RNA (pgRNA)&nbsp;has been&nbsp;recently&nbsp;found in&nbsp;patient blood.&nbsp;The&nbsp;serum&nbsp;pgRNA&nbsp;is hypothesized to function as a&nbsp;novel&nbsp;biomarker for the activity of&nbsp;HBV covalently-&nbsp;closed-circular DNA (cccDNA), which is&nbsp;the&nbsp;intracellular&nbsp;persistent form of HBV DNA and the template&nbsp;for producing&nbsp;viral proteins responsible for the&nbsp;chronic&nbsp;virulence of HBV.&nbsp;However, the molecular characteristics of serum HBV RNA remains&nbsp;elusive.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design&nbsp;</strong><strong>and&nbsp;</strong><strong>Project Methods:</strong><strong>&nbsp;</strong>HBV RNA were extracted from<strong>&nbsp;</strong>patient’s&nbsp;sera.&nbsp;RT-PCR and 3’ RACE were utilized to amplify the internal sequence and 3’ terminus of HBV pgRNA, respectively. The PCR products&nbsp;were&nbsp;gel purified&nbsp;and cloned into T vector for&nbsp;sequencing.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><strong>&nbsp;</strong>After comparing&nbsp;the sequencing data&nbsp;to the&nbsp;reference&nbsp;HBV sequence, we&nbsp;found&nbsp;that the&nbsp;serum HBV&nbsp;RNA&nbsp;are&nbsp;spliced fragments&nbsp;of the original&nbsp;intracellular&nbsp;full-length pgRNA.&nbsp;The prevalence of the fragmented&nbsp;serum&nbsp;pgRNA was found in greater concentrations in untreated patients, and&nbsp;the ratios of different spliced forms of serum HBV RNA vary during the course of antiviral treatment.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><strong>&nbsp;</strong>Our study demonstrated that the serum HBV RNA are spliced/truncated forms of pgRNA, indicating that the RNA-containing virion is&nbsp;noninfectious. The characterization of serum HBV RNA sequence provides important insights into the assay design for serum HBV RNA&nbsp;detection.&nbsp; Future study will focus on the mechanism underlying the selective&nbsp;egress&nbsp;of spliced pgRNA-containing virus particles.&nbsp;</p> 2018-12-07T14:30:03-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22801 Starting from the Roots: Observing Healthcare and Population Health Endeavors in a Lower Middle Income Country 2019-01-08T13:21:46-05:00 Madalyn Vonderohe imprs@iupui.edu <p><strong>The&nbsp;Slemenda&nbsp;Scholarship</strong><strong>:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p>The&nbsp;Slemenda&nbsp;Scholarship is a program&nbsp;that was developed in 1998&nbsp;for rising second year medical students&nbsp;in order for them&nbsp;to gain experience in the field of global health through the context of the AMPATH Consortium in Eldoret, Kenya. As a medical professional aspiring to work internationally, it is an invaluable experience to observe practices in a well-established partnership such as the one between Moi Teaching and Referral Hospital, Moi University, and Indiana University.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Community Experiences:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p>The first half of the summer was spent visiting and participating in various AMPATH initiatives. This included rounding on the medical, surgical, gynecological, and pediatric wards, volunteering with the child life team, visiting community health and microfinance projects, observing rural HIV clinics, and working at a school developed for street children in Eldoret.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Primary Project:&nbsp;</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p>The second half of the summer was spent working with the Maternal Newborn and Child Health team, specifically in the Reproductive Health department. I worked as a research assistant for a new project seeking to develop an antenatal care clinic for young girls aged 10-19 in&nbsp;Uasin&nbsp;Gishu County at the Rafiki Centre for Adolescents at Moi Teaching and Referral Hospital. I developed recruitment materials and a database for qualitative and quantitative data collection for the project.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Moving Forward</strong><strong>:&nbsp;</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p>On returning to Indiana, it is my goal to champion the work of the AMPATH Consortium and attempt to ensure its longevity through the next generation of globally-minded physician-scientists. I will take the lessons I learned and observations I made in this setting and work to apply them to improving healthcare in underserved areas in our own community as well.&nbsp;&nbsp;</p> 2018-12-07T14:30:41-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22802 Enhanced survival of lethally irradiated mice given pegylated G-CSF, GM-CSF, and IL-11 with lisinopril via modulation of the hematopoietic cytokines TGF[Symbol]-1 and RANTES 2019-01-08T13:21:46-05:00 Brett Walker imprs@iupui.edu Tong Wu imprs@iupui.edu Paul A. Plett imprs@iupui.edu Hui L. Chua imprs@iupui.edu Hailin Feng imprs@iupui.edu Christie Orschell imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><strong>&nbsp;</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>We have previously shown increased survival in mice given pegylated growth factors, G-CSF, GM-CSF, and IL-11 (triple combo, TC), with lisinopril compared to TC alone in the hematopoietic acute radiation syndrome (H-ARS). This experiment investigated the mechanism behind the survival benefit. We hypothesized lisinopril regulates inflammatory cytokines hence increasing quiescence of primitive bone marrow cells.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experim</strong><strong>ental Design or Project Methods:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>C57BL/6 mice were exposed to LD90/30 total body irradiation (TBI). The irradiated mice were given a TC injection on day 1, and lisinopril was administered in drinking water beginning on day 7. Mice were euthanized on day 10. Flow cytometry was used to analyze bone marrow cell cycle and&nbsp;Bioplex&nbsp;was used to analyze cytokines in bone marrow supernatant.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><strong>&nbsp;</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Treatment with&nbsp;TC+lisinopril&nbsp;significantly decreased&nbsp;the level of the pro-inflammatory cytokine RANTES compared with vehicle mice (Veh) and TC alone (TC+Liso&nbsp;vs. Veh: 3.6 vs. 7.8&nbsp;pg/mL,&nbsp;<em>p</em>&lt;0.01;&nbsp;TC+Liso&nbsp;vs. TC: 3.6 vs. 5.2&nbsp;pg/ml,&nbsp;<em>p</em>&lt;0.01).&nbsp;TC+lisinopril&nbsp;increases levels of the pro-quiescence cytokine TGF-[Symbol]1, compared with Veh and TC alone (TC+Liso&nbsp;vs. Veh: 92.8 vs. 45.6&nbsp;pg/mL,&nbsp;<em>p</em>&lt;0.05;&nbsp;TC+Liso&nbsp;vs. TC: 92.8 vs. 44.7&nbsp;pg/ml,&nbsp;<em>p</em>&lt;0.01). TC alone had lower percentages of quiescent Lin- primitive bone marrow cells (G0+G1) than non-irradiated (NI) mice (75.7 vs. 85.2%,&nbsp;<em>p</em>&lt;0.05), whereas there is no difference between&nbsp;TC+Liso&nbsp;and NI mice (83.0 vs. 85.2%,&nbsp;<em>p</em>=0.44).<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>The increased survival of H-ARS mice given lisinopril might&nbsp;be due to the regulation of&nbsp;TGF-[Symbol]1 and RANTES levels&nbsp;in the bone marrow leading to quiescence of primitive bone marrow cells.</p> 2018-12-07T14:31:13-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22803 BabyNoggin Pre-implementation Phase: Understanding How Clinical Teams and Parents Will Respond to BabyNoggin 2019-01-08T13:21:46-05:00 Sarah W. Watkins imprs@iupui.edu Elizabeth Z. Chen imprs@iupui.edu Katie Swec imprs@iupui.edu Jordan Huskins imprs@iupui.edu Jin Lee imprs@iupui.edu Andrew D. Miller imprs@iupui.edu Nerissa S. Bauer imprs@iupui.edu <p><strong>Background</strong><strong>&nbsp;</strong><strong>and&nbsp;</strong><strong>Purpose</strong><strong>:</strong>&nbsp;Mobile health&nbsp;(mHealth)&nbsp;apps hold potential to transform healthcare, but their adoption in clinical settings&nbsp;takes time&nbsp;and how providers and families use them is unknown.&nbsp;Three&nbsp;clinics at Riley Hospital for Children are preparing to implement&nbsp;<em>BabyNoggin</em>, an app that collects developmental screening tools typically collected&nbsp;via paper forms.&nbsp;The&nbsp;purpose of this study was&nbsp;two-fold: 1)&nbsp;to&nbsp;understand pre-implementation processes and provider perspectives of integrating&nbsp;<em>BabyNoggin&nbsp;</em>into clinic workflow;&nbsp;and&nbsp;2)&nbsp;to&nbsp;examine&nbsp;parental&nbsp;attitudes towards&nbsp;the use of apps&nbsp;for child development.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Project Methods:</strong>&nbsp;Pre-implementation clinical observations&nbsp;of workflow were performed in participating clinics.&nbsp;Semi-structured interviews&nbsp;informed by the Consolidated Framework for Implementation Research (CFIR) were conducted&nbsp;with each clinical team&nbsp;to understand&nbsp;perceived implementation facilitators and barriers. Lastly, parents&nbsp;with children aged 0-5&nbsp;were recruited from&nbsp;study&nbsp;clinics&nbsp;and&nbsp;social media to&nbsp;participate in a 26-item&nbsp;survey&nbsp;to&nbsp;gauge&nbsp;their attitudes towards using apps&nbsp;in place of paper screening forms and for tracking&nbsp;their child’s&nbsp;development.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Results:</strong>&nbsp;Implementation&nbsp;workflows&nbsp;were&nbsp;co-created&nbsp;with&nbsp;each clinical team&nbsp;that&nbsp;should not increase&nbsp;visit length. Five CFIR interviews&nbsp;highlighted facilitators and barriers towards implementation of&nbsp;<em>BabyNoggin</em>&nbsp;to be considered during implementation.&nbsp;Out of 199 parents&nbsp;who completed the survey,&nbsp;72.9%&nbsp;(n=145) reported a higher likelihood of downloading a child health app that was recommended by&nbsp;their&nbsp;pediatrician.&nbsp;&nbsp;&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p><strong>Conclusion and&nbsp;</strong><strong>Future Steps</strong><strong>:</strong>&nbsp;This study constituted the pre-implementation&nbsp;phase&nbsp;of&nbsp;a larger&nbsp;project involving the implementation of&nbsp;<em>BabyNoggin</em>.&nbsp;Future&nbsp;research&nbsp;will use these findings as a guide during implementation.&nbsp;</p> 2018-12-07T14:31:45-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22804 A Case-Based Tropical Medicine Curriculum for Interdisciplinary Global Health Track Residents 2019-01-08T13:21:46-05:00 Damon E. Webb imprs@iupui.edu Will Northquist imprs@iupui.edu Jenny Baenziger, MD imprs@iupui.edu <p><span class="TextRun SCXW158968821" lang="EN-US" xml:lang="EN-US"><span class="NormalTextRun SCXW158968821">Global health education is essential for equipping physicians to improve population health both at home and abroad. Global health is a multidisciplinary specialty with physicians who come from many backgrounds, making it important to reinforce concepts in its education that might not have been the focus of their previous training. Tropical medicine, and its focus on infectious disease, is one area of global health that many physicians may not have focused on extensively. We developed a curriculum for tropical medicine for residents in the Indiana University Interdepartmental Global Health Track, a 2-</span></span><span class="TextRun SCXW158968821" lang="EN-US" xml:lang="EN-US"><span class="NormalTextRun SCXW158968821">3 year</span></span><span class="TextRun SCXW158968821" lang="EN-US" xml:lang="EN-US"><span class="NormalTextRun SCXW158968821">&nbsp;co-curricular focus on global health with residents from Family Medicine, Internal Medicine, Med-</span></span><span class="TextRun SCXW158968821" lang="EN-US" xml:lang="EN-US"><span class="NormalTextRun SCXW158968821">Peds</span></span><span class="TextRun SCXW158968821" lang="EN-US" xml:lang="EN-US"><span class="NormalTextRun SCXW158968821">, Pediatrics, OBGYN, EM, and others. Research has shown that case-based learning (CBL) is effective in engaging students and faculty compared to other educational methods. It is believed that utilizing CBL in delivering a tropical medicine curriculum to these residents will develop proficiency in the subject over the 8 sessions developed. Residents will learn about a variety of infectious diseases in each session by working through a case, engaging in critical thinking in small groups, then taking a quiz. Following completion of all sessions, they will be complete a summative test and a survey subjectively assessing the curriculum. We hope this novel curriculum will prove effective in teaching the essentials of tropical medicine to Global Health Track residents and will serve as an example for the development of other tropical medicine curricula.</span></span></p> 2018-12-07T14:32:21-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22805 Gabapentin Targeting and Bone Mineralization Defects: Proposed mechanism for increased fracture risk in patients taking GBP-class anti-epileptic drugs 2019-01-08T13:23:31-05:00 Jonathan A. Wheeler imprs@iupui.edu Megan L. Noonan imprs@iupui.edu William R. Thompson imprs@iupui.edu Kenneth E. White imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Gabapentin (GBP) is an anti-epileptic&nbsp;drug and first-line&nbsp;therapy&nbsp;for neuropathic&nbsp;pain prescribed to 43 million patients in the US.&nbsp;Unfortunately, GBP use is associated with&nbsp;metabolic bone disease,&nbsp;leading to a&nbsp;2&nbsp;to&nbsp;6-fold&nbsp;increased fracture incidence. Until now, the pathophysiology of this drug-induced bone loss&nbsp;was&nbsp;unknown. We hypothesize&nbsp;that the impaired bone mineralization and skeletal defects is a result of downstream effects&nbsp;of&nbsp;GBP targeting of the[Symbol]<span data-fontsize="11">2</span>[Symbol]<span data-fontsize="11">1</span>&nbsp;subunit, the only known GBP receptor.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Project Methods:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><em>I</em><em>n vitro</em><em>:</em>&nbsp;Murine mesenchymal progenitor cells (MPC-2)&nbsp;were treated with GBP&nbsp;doses&nbsp;varying from&nbsp;0.5mM to 50mM&nbsp;while undergoing osteoblast differentiation for 1 or&nbsp;2 weeks.&nbsp;Mineralization was&nbsp;assessed&nbsp;by Alizarin red stain.&nbsp;Gene expression was measured by RT-qPCR.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><em>In vivo:</em>&nbsp;The bone phenotype&nbsp;of mice lacking the&nbsp;[Symbol]<span data-fontsize="11">2</span>[Symbol]<span data-fontsize="11">1</span>&nbsp;subunit&nbsp;was analyzed by longitudinal DXA analyses&nbsp;and examined&nbsp;histologically.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><em>In vitro</em>:&nbsp;MPC-2 cells&nbsp;treated with 50mM GBP&nbsp;while&nbsp;differentiating for 1&nbsp;and 2&nbsp;weeks&nbsp;had decreased&nbsp;osteoblast mineralization&nbsp;and&nbsp;a&nbsp;7-fold reduction&nbsp;and 4 fold reduction, respectively,&nbsp;in DMP1.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><em>In vivo</em>:&nbsp;Male and&nbsp;female&nbsp;[Symbol]<span data-fontsize="11">2</span>[Symbol]<span data-fontsize="11">1</span>&nbsp;knockout&nbsp;mice showed a significant decrease in whole body&nbsp;longitudinal (6 wk – 18 wk)&nbsp;bone mineral density (BMD)&nbsp;in males (p&lt;0.001) and females&nbsp;(p=0.014), along with severe osteomalacia,&nbsp;displaying unmineralized osteoid&nbsp;in the trabecular compartment of the distal femoral metaphyses.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>The impaired&nbsp;mineralization&nbsp;observed following&nbsp;[Symbol]<span data-fontsize="11">2</span>[Symbol]<span data-fontsize="11">1</span>&nbsp;deletion, coupled with reduced differentiation of&nbsp;MPC-2 cells treated with GBP&nbsp;suggests&nbsp;that&nbsp;GBP regulates bone quality through a&nbsp;novel mechanism&nbsp;influencing&nbsp;phosphate wasting&nbsp;or&nbsp;1,25&nbsp;vitamin&nbsp;D deficiency&nbsp;leading to&nbsp;fracture.&nbsp;With this awareness&nbsp;physicians can&nbsp;monitor these&nbsp;patients for bone mass&nbsp;loss&nbsp;and prescribe drugs&nbsp;to&nbsp;prevent&nbsp;AED-mediated fracture.</p> 2018-12-07T00:00:00-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22806 Effects of Temperature and Separation on the Retained Coagulability of Human Blood Utilizing Thromboelastography 2019-01-08T13:21:45-05:00 Michael A. Wiley, MS imprs@iupui.edu Nathan J. Alves, PhD imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335551550&quot;:6,&quot;335551620&quot;:6,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Thromboelastography&nbsp;is&nbsp;torsional method of assessing coagulation efficiency (e.g. rate of clot formation and maximum clot strength) by measuring the viscosity changes of blood under low-shear stress.&nbsp;Limited&nbsp;research has been performed to date&nbsp;on how centrifugation and storage of whole blood affects the&nbsp;coagulability&nbsp;when recombined.&nbsp;We hypothesized that centrifuged blood that&nbsp;was&nbsp;stored at its component-specific ideal temperatures would produce a clot with the same clotting characteristics as whole blood.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335551550&quot;:6,&quot;335551620&quot;:6,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Experimental Design or Project Methods:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335551550&quot;:6,&quot;335551620&quot;:6,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Whole blood samples were&nbsp;collected from&nbsp;healthy&nbsp;volunteers into citrated tubes and were assigned to&nbsp;the following&nbsp;conditions:&nbsp;whole at 25[Symbol]C,&nbsp;whole at 4[Symbol]C, and&nbsp;centrifuged&nbsp;and stored&nbsp;as&nbsp;RBCs, platelets, and plasma (at 4[Symbol]C,&nbsp;25[Symbol]C, and -20[Symbol]C, respectively)&nbsp;and then recombined.&nbsp;TEG tracings&nbsp;for each condition&nbsp;were&nbsp;obtained over the course of three&nbsp;weeks. We also explored how freezing and thawing whole blood samples and its components&nbsp;affected clotting.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335551550&quot;:6,&quot;335551620&quot;:6,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335551550&quot;:6,&quot;335551620&quot;:6,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>When compared to room temperature and refrigerated whole blood, separated&nbsp;blood maintains&nbsp;its&nbsp;normal&nbsp;physiologic&nbsp;clotting&nbsp;dynamics&nbsp;and kinetics&nbsp;for a longer period of time.&nbsp;Whole blood at&nbsp;25[Symbol]C&nbsp;maintains maximum clot strength for approximately one week post draw, whereas freezing whole blood drastically reduces&nbsp;coagulability.&nbsp;Additionally, we&nbsp;discovered that there is no&nbsp;practical&nbsp;difference&nbsp;in&nbsp;the clotting parameters between the first blood draw and&nbsp;subsequent&nbsp;draws.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335551550&quot;:6,&quot;335551620&quot;:6,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><span data-ccp-props="{&quot;134233279&quot;:true,&quot;201341983&quot;:0,&quot;335551550&quot;:6,&quot;335551620&quot;:6,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Our&nbsp;study demonstrates the viability of storing blood&nbsp;in its components and recombining&nbsp;them at a later date while minimally affecting its clotting ability, thereby potentially reducing wasted blood products and the need for multiple blood draws for coagulation studies.&nbsp;</p> 2018-12-07T14:33:40-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22807 Quantifying the effects of mechanical signals on musculoskeletal quality in a model of complete estrogen deprivation 2019-01-08T13:21:45-05:00 Reid Wilson imprs@iupui.edu Gabriel M. Pagnotti, PhD imprs@iupui.edu Khalid S. Mohammad, MD, PhD imprs@iupui.edu Theresa A. Guise, MD imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>Post-menopausal, estrogen-receptor positive breast cancer patients&nbsp;are&nbsp;treated with aromatase inhibitors (AIs) to limit tumor progression; however,&nbsp;this causes&nbsp;adverse musculoskeletal effects. Zoledronic acid (ZA) is prescribed to inhibit bone&nbsp;resorption.&nbsp;Mechanical&nbsp;signals, delivered&nbsp;via low&nbsp;intensity vibration (LIV), stimulate bone formation.&nbsp;We hypothesize that combining LIV&nbsp;with&nbsp;ZA will mitigate bone loss in a murine model of&nbsp;complete estrogen-deprivation more effectively than either treatment alone.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559731&quot;:720,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Project Methods:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>21-week-old C57BL/6 mice&nbsp;(n=20/group)&nbsp;were ovariectomized, receiving&nbsp;daily letrozole&nbsp;injections (OVX/AI) with LIV&nbsp;(OVX/AI+LIV), ZA&nbsp;(OVX/AI+ZA), LIV and ZA (OVX/AI+LIV/ZA) or&nbsp;underwent&nbsp;sham surgery with daily&nbsp;PBS (vehicle)&nbsp;injections (SH-OVX)&nbsp;for 22 weeks. Longitudinal dual energy X-ray absorptiometry (DEXA)&nbsp;and&nbsp;micro-computed tomography scans were analyzed for changes in body composition and bone microarchitecture, respectively.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559731&quot;:720,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p>OVX/AI reduced&nbsp;whole body (p&lt; 0.0001)&nbsp;and&nbsp;lumbar spine&nbsp;(p&lt;0.0001)&nbsp;bone mineral density (BMD)&nbsp;as compared to SH-OVX&nbsp;by 11% and 28%, respectively, as measured via DEXA. At 22w,&nbsp;OVX/AI+LIV/ZA&nbsp;had greater&nbsp;BMD&nbsp;across both regions-of-interest&nbsp;relative to OVX/AI (p&lt;0.0001).&nbsp;Cortical&nbsp;bone&nbsp;area fraction (p&lt;0.0001)&nbsp;and cortical thickness (p[Symbol]0.001)&nbsp;in distal femora&nbsp;decreased&nbsp;by 8%&nbsp;and 9%, respectively,&nbsp;in OVX/AI relative to SH-OVX. In&nbsp;OVX/AI+LIV/ZA, these parameters were greater&nbsp;relative to OVX/AI (p[Symbol]0.0001).&nbsp;OVX/AI+ZA and&nbsp;OVX/AI+LIV&nbsp;groups&nbsp;were not significantly different from OVX/AI in either cortical&nbsp;bone&nbsp;area fraction or cortical thickness.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:0,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact:</strong><span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:259}">&nbsp;</span></p> <p>Complete estrogen-deprivation&nbsp;reduced&nbsp;bone&nbsp;mineral density and&nbsp;altered&nbsp;microarchitecture.&nbsp;Mechanical signals&nbsp;provided via&nbsp;LIV combined with ZA prevent&nbsp;bone loss in aged estrogen-deprived mice.&nbsp;Combining these treatment strategies may reduce skeletal morbidity in breast cancer patients.</p> 2018-12-07T14:34:10-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22809 Blood Loss in Primary and Aseptic Revision Total Knee Arthroplasty: A Retrospective Matched Cohort Analysis 2019-01-08T13:21:45-05:00 Honglin Xiao, BS imprs@iupui.edu Evan R. Deckard, BSE imprs@iupui.edu Mary Ziemba-Davis, BA imprs@iupui.edu Michael R. Meneghini, MD imprs@iupui.edu <p><strong>Background and Hypothesis:</strong><strong>&nbsp;&nbsp;</strong>While blood loss in primary TKA is well-characterized, there is a paucity of data on blood loss in aseptic revision TKA.&nbsp; In this study, we&nbsp;hypothesized&nbsp;that&nbsp;revision TKAs&nbsp;would have increased blood loss compared&nbsp;to matched primary&nbsp;TKAs.<span data-ccp-props="{&quot;134233279&quot;:true,&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Project Methods:</strong><strong>&nbsp;&nbsp;</strong>Two-hundred-ninety&nbsp;consecutive&nbsp;revision TKAs&nbsp;performed&nbsp;between 2010 and 2017&nbsp;were retrospectively&nbsp;reviewed&nbsp;and&nbsp;matched to&nbsp;primary TKAs&nbsp;on surgeon, age, sex, BMI, and ASA&nbsp;Score.&nbsp;&nbsp;Seventy-four revision TKAs were excluded for&nbsp;factors&nbsp;affecting&nbsp;blood loss.&nbsp;Potential covariates&nbsp;affecting blood loss were compiled from the medical record.&nbsp;Outcomes including&nbsp;total blood loss, drain output&nbsp;rate, and change in hemoglobin levels&nbsp;from preoperative to&nbsp;postoperative day one&nbsp;were&nbsp;assessed.<span data-ccp-props="{&quot;134233279&quot;:true,&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Results:</strong><strong>&nbsp;&nbsp;</strong>Two-hundred-sixteen&nbsp;revision TKAs matched to&nbsp;216 primary TKAs were analyzed.&nbsp; Multivariate analysis&nbsp;showed&nbsp;no difference in blood loss metrics comparing primary and revision TKAs.&nbsp;&nbsp;However, increased tourniquet&nbsp;time (<em>p</em>=0.001), elevated BMI&nbsp;(<em>p</em>=0.002), male sex&nbsp;(<em>p</em>&lt;0.001), and lack of topical TXA&nbsp;(<em>p</em>=0.005) significantly increased total blood loss.&nbsp;&nbsp;Similar results were found&nbsp;for increased&nbsp;drain output rate&nbsp;in addition to&nbsp;lack of&nbsp;intravenous TXA (<em>p</em>&lt;0.001) and a trend for lower age&nbsp;(<em>p</em>=0.073).&nbsp; Increased tourniquet time (<em>p</em>=0.004)&nbsp;and lack of topical TXA (<em>p</em>=0.002) correlated&nbsp;with a greater drop in hemoglobin postoperatively.<span data-ccp-props="{&quot;134233279&quot;:true,&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:240}">&nbsp;</span></p> <p><strong>Conclusion</strong><strong>&nbsp;and Potential Impact</strong><strong>:</strong><strong>&nbsp;&nbsp;</strong>Primary and revision TKAs&nbsp;showed no difference in&nbsp;blood&nbsp;loss.&nbsp;&nbsp;However,&nbsp;increased&nbsp;tourniquet time&nbsp;and withholding topical TXA significantly increased&nbsp;total blood loss, drain output&nbsp;rate, and&nbsp;change&nbsp;in hemoglobin levels.&nbsp;This data continues to support emphasizing procedural efficiency and TXA use in revision TKA.</p> 2018-12-07T14:34:38-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22819 This Story Needs to Be Told: Formative Research on Using Animated Storytelling to Address Prospective Minority Clinical Trials Participants’ Need for Comprehensive Knowledge 2019-01-08T13:21:45-05:00 Stephanie M. Younker imprs@iupui.edu Katherine E. Ridley-Merriweather imprs@iupui.edu <p><strong>Background:&nbsp;</strong>The Komen Tissue Bank (KTB), a clinical trial that collects women’s healthy breast tissue for use as research study controls, currently stores samples demonstrating a noted paucity of minority specimens. Studies have shown minority groups’ participation in clinical trials is dependent upon the groups’ knowledge about the associated research. This study’s purpose is to conduct formative research on animated storytelling’s effectiveness as a communication tool to address minority&nbsp;groups’&nbsp;expressed need for knowledge and encourage participation in cancer clinical trials.&nbsp;<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:276}">&nbsp;</span></p> <p><strong>Methods:</strong>&nbsp;I re-coded data previously gathered from a KTB study to evaluate the perceptions of Latinas (n=14) and Asian Americans (n=17) toward breast tissue donation. Extensive review of the current literature yielded data concerning African Americans’ outlooks toward clinical trial participation,&nbsp;and&nbsp;also&nbsp;illustrated the efficacy of using narratives and animation as communication and education tools.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:276}">&nbsp;</span></p> <p><strong>Results:</strong>&nbsp;The literature review clearly illuminated the importance of storytelling in minority cultures and suggested the success of using narratives as communication tools. We anticipate our findings could be influenced by a) minorities’ lack of, and need for, comprehensive knowledge, b) previously obscured participation barriers, and c) animated storytelling as an effective delivery method.<span data-ccp-props="{&quot;201341983&quot;:0,&quot;335559739&quot;:160,&quot;335559740&quot;:276}">&nbsp;</span></p> <p><strong>Projected Conclusion and Potential Impact:&nbsp;</strong>Using an animated storytelling communication tool may successfully increase knowledge about, and comfort with, participation in a cancer clinical trial. The next phase, an animated video production, will tell the comprehensive story of healthy breast tissue donation. The use of this tool could help increase minority participation in cancer prevention and cancer clinical trials.</p> 2018-12-07T14:35:16-05:00 ##submission.copyrightStatement## http://journals.iupui.edu/index.php/IMPRS/article/view/22820 A Physiological Role for a Moonlighting Protein in Lipopolysaccharide-induced Endotoxemia 2019-01-08T13:21:44-05:00 Kirsten Zborek imprs@iupui.edu Daniel Lee imprs@iupui.edu Adam Pajakowski imprs@iupui.edu Jacob Slack imprs@iupui.edu Joseph Park imprs@iupui.edu June Park imprs@iupui.edu Margaret Schwarz imprs@iupui.edu <p><strong>Background and&nbsp;</strong><strong>Hypothesis</strong>: The&nbsp;pathogenesis of&nbsp;Bronchopulmonary Dysplasia (BPD) is multifactorial leading to inflammation.&nbsp;In BPD,&nbsp;Endothelial-Monocyte Activating Polypeptide II (EMAP II, encoded by&nbsp;<em>Aimp1</em>), a moonlighting pro-inflammatory&nbsp;cytokine,&nbsp;is initially found in bronchiolar club cells followed by intra-alveolar GAL-3+ macrophages.&nbsp;Sustained EMAP II&nbsp;mimics BPD, invoking inflammation,&nbsp;alveolar simplification, and macrophage recruitment. Targeted ablation of EMAP&nbsp;II in the recruited macrophages&nbsp;may&nbsp;dampen&nbsp;innate immune response.<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Experimental Design</strong>:&nbsp;Gender-matched, aged-matched&nbsp;littermate&nbsp;mice with myeloid-cell specific ablation of&nbsp;<em>Aimp1</em>&nbsp;(Lyz2-Cre;Aimp1<span data-fontsize="11">flox/</span><span data-fontsize="11">flox</span>, denoted as&nbsp;<em>Aimp1</em><span data-fontsize="11">Δ/Δ</span>) or without&nbsp;(control)&nbsp;were subjected to&nbsp;lipopolysaccharide (LPS)-endotoxemia. Survival rates of co-housed or singly housed mice were measured over 72 hours following a lethal dose (15 mg/kg). Clinical scores (0-6) based on the integrity of their locomotion, fur, and eyes were assigned&nbsp;every 2 hours. Blood and bone marrow smears, average bodyweights, spleen-weights to bodyweights and liver-weights to bodyweights were analyzed.<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Results</strong>:&nbsp;There were no baseline differences in bodyweight, spleen&nbsp;weight:bodyweight, liver&nbsp;weight:bodyweight&nbsp;(p-val&nbsp;= 0.42, 0.46, 0.64).&nbsp;Representative bone marrow and&nbsp;blood smears&nbsp;showed no notable difference.&nbsp;<em>Aimp1</em>[Symbol]<span data-fontsize="11">/</span>[Symbol]<span data-fontsize="11">&nbsp;</span>male&nbsp;mice co-housed (dose 15 mg/kg) but not singly housed survived longer than their littermates (median survival: hours);&nbsp;<em>Aimp1</em>[Symbol]<span data-fontsize="11">/</span>[Symbol]<span data-fontsize="11">&nbsp;</span>female mice showed a survival advantage&nbsp;(median survival: hours) with lower clinical scores than their littermates.&nbsp;The kinetics of&nbsp;NFKBIA/I[Symbol]B degradation was similar between&nbsp;<em>Aimp1</em>[Symbol]<span data-fontsize="11">/</span>[Symbol]&nbsp;and control peritoneal macrophages in response to LPS, although there was a higher basal amount in&nbsp;<em>Aimp1</em>[Symbol]<span data-fontsize="11">/</span>[Symbol].<span data-ccp-props="{}">&nbsp;</span></p> <p><strong>Conclusion and Potential Impact</strong>:&nbsp;Aimp1/EMAP II does play a&nbsp;positive&nbsp;feedback role in innate immunity, potentially in a metabolically and&nbsp;gender-specific role of&nbsp;<em>Aimp1</em>&nbsp;which remain to be explored.</p> 2018-12-07T14:35:57-05:00 ##submission.copyrightStatement##