https://journals.iupui.edu/index.php/IMPRS/issue/feedProceedings of IMPRS2024-02-13T13:47:21-05:00Anne Nguyenimprs@iupui.eduOpen Journal Systems<p>The 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>https://journals.iupui.edu/index.php/IMPRS/article/view/27695Abortion in The United States – The Impact of Changing Legislation on Prescription Patterns in Pediatric and Maternal Populations2023-11-20T15:23:00-05:00Camryn ZuchLindsey KirkpatrickPengyue ZhangSara K. Quinney<p><strong>Background and Hypothesis</strong>: Changes in healthcare legislation may have unintended consequences for patient care at the individual level. Following the Supreme Court case Dobbs vs Jackson Women’s Health Organization in 2022 resulting in the reversal of Roe V. Wade, many states enacted new abortion legislation. Currently, there are many restrictions and barriers to abortion and reproductive care that may limit access across the country. Given the volatile political environment surrounding abortion legislation, there may be some confusion among clinicians about the legality of abortion and miscarriage care. Abortion legislation and restriction may have an impact on other areas of healthcare, including prescription patterns of Category X medications in women of childbearing age. Based on the current legislation, we hypothesize that prescription rates of Category X medications will decrease while prescription rates of birth control methods will increase.</p> <p><strong>Project Methods:</strong> Real world data on prescribing patterns will be obtained from IUH Cerner database and the Cerner Learning Health Network. Demographic information including age, race and insurance status will be obtained. Data will be analyzed to assess trends in prescription patterns for women of childbearing age that correlate with dates of changing abortion legislation.</p> <p><strong>Potential Impact</strong>: The findings from this study will help direct future research on medication prescription and administration in people of childbearing age. Results may also inform future policy changes surrounding women’s healthcare.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Camryn Zuch, Lindsey Kirkpatrick, DO, PhD, Pengyue Zhang, PhD, Sara K. Quinney, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27717YebC Modulates OspC and VlsE Inverse Regulation and VlsE Expression in Persistent Lyme Disease2023-12-05T09:31:11-05:00Andrew ZossSajith RaghunandananX. Frank Yang<p><strong>Background & Hypothesis: </strong>Lyme disease, caused by the bacterium <em>Borrelia burgdorferi</em>, is the most common vector-borne infectious disease in the United States. Although easily treated with antibiotics, undiagnosed cases may develop into persistent infections with complications including Lyme carditis, neuroborreliosis, & arthritis. VlsE antigen variation is one of the major mechanisms employed by <em>B. burgdorferi</em> to establish persistent infection. We hypothesize that YebC modulates VlsE expression and antigen variation, enabling the shift from acute to persistent infection.</p> <p><strong>Materials & Methods: </strong>C3H/HeN or C3H/SCID mice were infected with the <em>B. burgdorferi </em>strain 5A4NP1, <em>yebC</em> mutant, and <em>yebC</em> complement at a dose of 10<sup>5 </sup>or 10<sup>6</sup> spirochetes. Mice were sacrificed at days 7, 30, 60, and 90 post-infection and tissue samples were subjected to RNA and DNA extraction.</p> <p><strong>Results: </strong>YebC levels were closely associated with the upregulation of vlsE and the downregulation of <em>ospC</em> <em>in vitro</em> and <em>in vivo</em>. The <em>yebC</em> mutant displayed loss of infectivity in C3H/HeN mice, and reduced VlsE antigen variation.</p> <p><strong>Conclusion & Impact: </strong>This data demonstrates that YebC of B burgdorferi can regulate the frequency of <em>vlsE</em> recombination and modulates the inverse regulation of OspC and VlsE. This new factor may serve as an avenue for developing drugs which can target <em>vlsE</em> recombination to combat complications of persistent Lyme disease.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Andrew Zoss, Sajith Raghunandanan, X. Frank Yang, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27720Retrospective Analysis of COVID-19 Impact on Social + Emotional Development in Children of Low-Income Communities from Head Start2023-12-06T09:04:42-05:00Gabrielle S. LiSatya P. SanapatiAmy Han<p>Background:<br>Geminus Head Start is a federal program that works with children under five years old from low-income communities to promote school readiness. The organization in Northwest Indiana provided anecdotal data on delayed social and emotional development of children during the pandemic. Studies have shown that adverse childhood development can have a severe psychological and physiological impact on health outcomes into adulthood. However, there has been a lack of research on quantifying the extent of damage from the pandemic on our Head Start children, who mainly identify as Black/African American.</p> <p><br>Methods:<br>Geminus Head Start provided demographic data including race, postal codes and DECA for over 4650 students from 2019-2023. DECA, Devereux Early Childhood Assessment, is used by educators to evaluate children’s social emotional competence for early intervention. In this study, we are investigating the DECA categories, including initiative, self-control, and attachment/relationships. We analyzed DECA scores via ANOVA along with listening into the teacher focus groups.</p> <p><br>Results:<br>Students had increased attachment/relationship scores from the 2019-2020 school year to the 2020-2021 school year (36.69 to 44.59). However, following COVID-19 to the 2021-2022 and 2022-2023 school years, these scores dropped to 23.51. When looking at the second protective factor, self-regulation, the opposite trend was found. The scores went from 18.79 in 2019-2020 down to 14.68 in 2020-2021 and eventually up to 23.51 in 2021-2022.</p> <p><br>Conclusion:<br>Like most institutions, the pandemic has created a time of isolation and instability for our children and their families. In particular, these children have not been able to access adequate conditions to develop emotional and social maturity. Lacking this development can lead to several negative health outcomes as it may impact mental health and the ability to create healthy supportive networks.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Gabrielle Li, Satya P. Sanapati, Amy Han, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27721Clinical Features for Detecting Diabetic Macular Edema using Artificial Intelligence2023-12-06T09:19:53-05:00Jeffrey LiuDoaa Hassan SalemHunter JillSarath Chandra JangaAmir Hajrasouliha<p>Background:<br>Vision is a valuable part of life: influencing our perception of the world and of memories. Diabetes, and more specifically, Diabetic Retinopathy (DR) can affect our vision, taking away sight potentially permanently if left untreated. Currently, Diabetic Retinopathy is the leading cause for adult blindness and will continue to rise with increasing prevalence of adult diabetes. Diabetic Macular Edema (DME), a complication of DR, is diagnosed by ophthalmologists using optical coherence tomography (OCT); however, the sheer amount of DME-related imaging creates a time strain on ophthalmologists, creating a demand to further optimize the image reading process. In this study, we hypothesize that increasing the rate and ease of diagnosing DME by introducing artificial intelligence-based methods in primary medical clinics will increase the long-term preservation of ocular health in diabetic patients.</p> <p><br>Methods:<br>Due to the nature of our retrospective cohort study, consent was not acquired and images were also de-identified. We categorized 676 patient files by HbA1c, non-proliferative diabetic retinopathy (NPDR) severity, and proliferative diabetic retinopathy (PDR). Retinal OCT images were annotated to identify central macular edema, a common feature of DME. Retinal fundus images were also annotated to identify microaneurysms and hemorrhages, two additional features commonly used for detecting either DR or DME.</p> <p><br>Results:<br>A lesion features dataset was prepared to train our AI model. OCT and fundus imaging features were extracted and combined to train the AI model for DME detection. From annotations of the in-house Macular thickness dataset, it was seen that 167 patients had DME from the total 389 diabetic retinopathy patients.</p> <p><br>Conclusion:<br>We will continue to prepare more datasets like the macular thickness dataset for our AI. We predict that after our AI receives substantial training with the datasets, the AI will potentially demonstrate some capability of diagnosing DME, supporting its use in medical diagnostics.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Jeffrey Liu, Doaa Hassan Salem, Hunter Jill, Sarath Chandra Janga, Amir Hajrasouliha, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27722Factors Predictive of Surgical Success in Medial Rectus Resection/Advancement for Consecutive Exotropia2023-12-06T10:05:56-05:00Tate LockwoodTyler Knight<p>Background and Objective: Consecutive exotropia after unilateral or bilateral medial rectus recession is a common clinical problem. One surgical intervention to address the misalignment involves isolating and reattaching healthy muscle to the globe. The purpose of this study was determining factors indicative of surgical success in medial rectus resection and advancement with non-adjustable sutures for consecutive exotropia.</p> <p><br>Methods: Through retrospective chart review, 118 patients were identified to have consecutive exotropia using billing codes from June 2016 to October 2020 at Indiana University Health. 60 of these patients who maintained adequate follow-up either underwent the above intervention (n = 49) or underwent resection only (n = 11). Exclusion criteria included lack of medial rectus procedure or poor postoperative documentation. Patient demographics and data were gathered, including preoperative and intraoperative measurements, final postoperative deviation, and whether additional surgeries were necessary. Chi-squared and two-sample t-tests were performed to analyze the effect of each parameter on surgical success, defined as distance deviation ≤ 10 prism diopters of esotropia or exotropia at final postoperative visit.</p> <p><br>Results: Smaller total intraoperative adjustment–resection plus advancement–was significantly associated with surgical success (p = 0.044). Additionally, smaller preoperative deviations were significantly associated with patients who underwent unilateral surgery (p = 0.0093 near and 0.0021 distance).</p> <p><br>Conclusion: Patients with smaller preoperative deviations tended to have better outcomes, and those patients tended to have unilateral surgery. It is unclear whether a smaller deviation might have led surgeons to select unilateral medial rectus surgery or if the smaller deviation itself is a predictor of success. Relatively limited time of follow-up is a limitation in this study, as there is well-documented postoperative drift of increasing exotropia over time. A larger cohort or randomized controlled trial may provide additional insight that could increase the percentage of successful outcomes with a single surgery.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Tate Lockwood, Tyler Knight, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27723Impact of Comorbidities as Predictors on Hospital Length of Stay (LOS) and Mortality in Hip Fracture (HF) Patients in a Rural Community2023-12-06T10:22:14-05:00Gabrielle LutzThein Zhu<p>Purpose: Studies on HF at a rural health system area are rare. The research question is “Which demographic, preoperative variables would be independent predictors of outcomes on mortality and hospital LOS?”</p> <p><br>Methods: The design is a community-based cross-sectional study with risk factor analyses. We ascertained HF cases from hospital trauma center registry and Epic software. We employed both descriptive and analytic approaches including multivariable regression analyses of predictors on outcomes.</p> <p><br>Results: Of 201 HF patients, 85.6% occurred in 65 and above years (seniors). Among seniors, females consisted of 64.0% with mean age ± SD: 83.72 ± 7.56 years; extracapsular HF, 55.2%; specified falls, 51.7%; obesity, 15.2%; complication, 3.5%; surgery interventions, 80.8%; mortality within 1, 9.3%; 3, 11.6%; 6, 15.1%; and 12 months, 22.1% after hospital admission. Holding all other variables constant, no surgical intervention increased mortality risk within 1-month (OR=28.87, 95% CI: 4.43; 188.16), 3-months (OR=33.47; 95% CI: 5.24; 213.88), 6-months (OR=21.78; 95% CI: 3.67; 129.48), and 12-months (OR=4.17; 95% CI: 1.33;13.04) compared to surgical intervention; obesity increased 1-month mortality risk (OR=6.00; 95% CI: 1.06; 34.09) compared to no obesity; and patients transferred from community hospital compared to those who were not had an increased 1-month (OR= 8.54; 95% CI: 1.25; 58.13), 3-month (OR=15.31; 95% CI: 2.21; 106.16), 6-month (OR=21.19; 95% CI: 3.34; 134.43), and 12-month (OR=5.14; 95% CI: 1.85; 14.28) mortality risk. Hospital LOS was 3.06 days higher in obese patients than non-obese patients and 2.11 days higher in surgery greater than 48 hours when compared to surgery within 48 hours, holding all other variables constant.</p> <p><br>Conclusions and Potential Impact: We believe that surgical intervention decreases, and obesity increases HF mortality. Obesity and delayed surgical intervention increase hospital LOS. The results of this study have the potential benefit for improving community health of rural, elderly populations in northeast Indiana.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Gabrielle Lutz, Thein Zhu, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27724Investigating the Functional Impacts of Metabolic Disease Associated Immune-Vascular Interactions in Alzheimer’s Disease2023-12-06T10:36:11-05:00Garrett MaagHallel C. ParaisoHannah HuangI-Chen Ivorine Yu<p>Background and Hypothesis:<br>Alzheimer’s disease (AD) is an irreversible neurodegenerative disorder with undefined etiology and is the fifth leading cause of death worldwide. AD pathology is characterized by amyloid-beta (Aβ) plaques. Previous work demonstrated that alterations in the microvasculature are some of the earliest recognizable changes in AD, and that most patients with dementia have mixed vascular pathologies. We investigated the functional impacts of metabolic disease associated immune-vascular perturbation on the underlying mechanisms of AD.</p> <p><br>Methods:<br>Adult male Lepr<sup>db</sup>/J (db/db) were obtained from the Jackson Laboratory. Activated microglia and brain vessel density levels were assessed using immunofluorescence. Cerebral microvessels were isolated for RNA examination using qPCR, and FACS-based analysis of brain endothelial cells. Immunofluorescence of hAβ42 transport in microvessels were observed via confocal microscope. Quantification of images were performed using Fiji (NIH) software.</p> <p><br>Results:<br>Db/db mice brains displayed higher levels of activated microglia with increased soma area and decreased circularity (p<0.05). This confirms early vascular stress leads to increased immune cell activation. Brain vessel density analysis revealed a non-statistically significant trend with decreased density in db/db mice. Given that functional changes occur before structural changes, we shifted our examination to the microvasculature. Brain microvessels were isolated and validated and both qPCR and FACS results demonstrated increased levels of inflammatory mediators and cell adhesion molecules in db/db mice (p<0.05), confirming microvessel dysfunction and neuroinflammation. Finally, quantification of luminal area fluorescence demonstrated decreased hAβ42 transport in db/db mice (p<0.01), validating functional disturbance in the cerebral microvasculature.</p> <p><br>Conclusion and Impact:<br>The vascular risk factors of metabolic disease can lead to dysfunction and inflammation in cerebral microvasculature, causing accelerated progression of AD. Our results emphasize the contributory role of cerebral small vessel health in the origin and evolution of AD and present an opportunity for novel development of surrogate biomarkers and therapeutic treatments.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Garrett Maag, Hallel C. Paraiso, Hannah Huang, I-Chen Ivorine Yu, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27725Effects of Diet, Gender, and Age on Liver Metabolism Upon Feeding a High Fat Diet2023-12-06T10:52:03-05:00Justin J. MacNeillAjay K. YadavAlex KrylovNúria Morral<p>Background/Objective: Currently, 30% of the USA population has non-alcoholic fatty liver disease (NAFLD), a condition that is increasing in parallel with the global obesity epidemic and life expectancy and is a risk factor for type 2 diabetes and cardiovascular disease. Aberrant transcriptional control of genes is a hallmark of metabolic disease. Thus, it is of interest to characterize how diet, age, and sex impacts various metabolic and signaling pathways upon progression to NAFLD.</p> <p><br>Methods: A cohort of 7-week or 52-week-old male and female mice (n=8) were assigned a high-fat diet (HFD) or a low-fat diet (LFD) feeding regimen for 10 weeks, after which serum chemistries were obtained. Subsequently, gene expression in hepatic tissue samples was analyzed using RNA-seq and Western Blot.</p> <p><br>Results: In both males and females, HDL, LDL, and total cholesterol were significantly increased with HFD in both age groups. In females, there was no significant difference in fasting blood glucose and insulin levels between any groups, while in males, both markers were significantly increased with HFD. RNA-seq data showed significant changes in gene expression correlating with diet, gender, and age. KEGG pathway analysis showed clustering of genes in fatty acid oxidation and synthesis pathways in mice fed a HFD, without affecting cholesterol synthesis enzymes. In aged mice, genes involved in extracellular matrix-receptor interaction were among the most affected. In males and females, young and aged, Western Blot analysis showed decreased expression of lipogenic enzymes ATP-citrate lyase and fatty acid synthase with HFD, but no changes of enzymes of cholesterol synthesis, confirming the RNA-seq data. No significant alterations were observed in insulin signaling.</p> <p><br>Conclusion and Potential Impact: A HFD leads to a more severe phenotype in males than females, including increased fasting and non-fating glucose as well as insulin, and age exacerbates these abnormalities. Cholesterol is increased in both genders and is also exacerbated by age.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Justin J. MacNeill, Ajay K. Yadav, Alex Krylov, Núria Morral, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27726Detection of Bowel and Mesenteric Injuries Using Deep Learning Computer Vision Models2023-12-06T12:05:33-05:00Neal MahajanScott D. SteenburgPeter GundermanJohn BurnsArya Iranmanesh<p>Background/Objective:<br>While only seen in 1-5% of patients who undergo a CT (computed tomography) scan, blunt bowel and mesenteric injuries (BMI) are associated with significantly increased morbidity and mortality. A significant cause of the increased morbidity of BMI is due to the difficulty of diagnosis from clinical and imaging information which leads to delay in diagnosis. Accurate and timely diagnosis is vital to reduce the morbidity of BMI.</p> <p><br>Methods:<br>For this project, our primary objective is to create a binary prediction model that determines if a patient has BMI based on their abdominal CT scans. Due to the importance of the early and definitive diagnosis of BMI in trauma patients, an extension of this project will seek to introduce explainability into the model to highlight which features on the CT scan caused the model to make its prediction. The patients with BMI were sourced from a trauma registry that recorded trauma cases from IU Health with relevant diagnosis codes. The images from our search will be reduced to the relevant slices for diagnosis of BMI and then used to train an ML model to make<br>a yes/no prediction from the image. Once the model is trained, testing data will be evaluated on the model and the gradient vectors from the model during inference will be used to create a heatmap with GRAD-CAM that illustrates what portions of the image were relevant for the decision made by the algorithm.</p> <p><br>Future Directions:<br>Using the collected abdominal CTs, we can train our machine learning pipeline to detect BMI. Based on the performance of the model, we will determine if we need to collect more data. Then, we can evaluate the explainability of the model using GRAD-CAM and compare<br>performance of the ML model to the performance of expert and trainee radiologists.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Neal Mahajan, Scott D. Steenburg, Peter Gunderman, John Burns, Arya Iranmanesh, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27727Radiological Findings in Patients Presenting with Brief Resolved Unexplained Events (BRUEs)2023-12-06T12:31:03-05:00Stasia MallinAmogh KambalyalTara HolloranChristopher NewmanMegan Marine<p>Background/Hypothesis: Brief resolved unexplained events (BRUEs) are events in infants characterized by cyanosis, abnormal breathing, abnormal tone, and altered responsiveness. Practice guidelines define high-risk and low-risk BRUEs and do not recommend imaging in low-risk patients. We evaluated imaging in these patients and hypothesized that high-risk patients would have more imaging studies and abnormalities.</p> <p><br>Methods: Using the radiology information system, a retrospective review was performed between 2016-2022 for patients <1 year presenting with BRUE. Defined search terms were used to identify imaging within one week of presentation. Patients were evaluated for clinical presentation, medical history, physical examination, imaging studies ordered, and final diagnoses.</p> <p><br>Results: 126 patients were identified. 113 patients (46 female; 93 high-risk), between 3 and 355 days old (average age 97 days), met inclusion criteria. Imaging included chest radiographs (99), head CTs (24), brain MRIs (19), skeletal surveys (16), and others (22). There was no difference in the number of imaging studies obtained between these groups (p=0.423, Mann-Whitney U test). However, a greater proportion of high-risk patients had imaging abnormalities (p=0.023, Fisher’s exact test). Only 1/20 (5%) low-risk patients had abnormal imaging (PCR proven viral bronchiolitis). 26/93 (28%) high-risk patients had abnormal findings, most commonly on chest<br>radiographs (15), brain MRIs (9), head CTs (4), and skeletal surveys (3). 18/26 high-risk patients had imaging abnormalities leading to a diagnosis other than BRUE (viral bronchiolitis, bronchopulmonary dysplasia, nonaccidental trauma, perinatal HSV infection, ventricular septal defect, double aortic arch, intestinal malrotation, and neurofibromatosis). Overall, 7/93 (7.5%) high-risk BRUE patients had significant pathology.</p> <p><br>Conclusion: High-risk patients were more likely to have an imaging abnormality compared to low-risk patients, which is consistent with current imaging recommendations given only one low-risk imaging abnormality. Interestingly, 7.5% of the high-risk patients had significant pathology diagnosed by imaging.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Stasia Mallin, Amogh Kambalyal, Tara Holloran, Christopher Newman, Megan B. Marine, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27728One Hundred Percent Tumor Necrosis is Associated with Survival in Ewing Sarcoma2023-12-06T12:43:10-05:00Matthew MarleyChristopher Collier<p>Background and Objectives:<br>Ewing sarcoma is a primary malignancy affecting both bone and soft tissue. Following preoperative chemotherapy and surgical resection, histologic response (tumor necrosis) is correlated with patient survival. The most prognostic cutoff for tumor necrosis continues to be debated. The objective of this study was to explore several cutoffs and determine their prognostic value in a contemporary cohort of Ewing sarcoma patients.</p> <p><br>Methods:<br>The National Cancer Database was used to identify 564 patients with osseous and soft tissue tumors in the Ewing sarcoma family from 2010 to 2015. All patients had documented preoperative chemotherapy, surgical resection, and vital status. Survival was stratified by tumor necrosis using Kaplan Meier analysis. 356 patients with osseous tumors were included in multivariate logistic and cox regression analyses to identify predictors of histologic response and survival, respectively.</p> <p><br>Results:<br>In a combined soft tissue and osseous tumor cohort, there was a significant difference (p = 0.01, log-rank test) in overall survival between patients with 100% necrosis and patients with less than 100% necrosis. This was observed over the 5-year study period. Other cutoffs were not statistically different. In patients with osseous tumors, less than 100% necrosis was negatively associated with survival (HR 3.48 [95% CI 1.19-10.13]; p< 0.05), with only skip metastasis having a stronger negative association (HR 4.31 [95% CI 1.22-15.29]; p< 0.05). Male sex (OR 0.50 [95% CI 0.28-0.90]; p<0.05), tumors located in the axial skeleton (OR 0.30 [95% CI 0.12- 0.77]; p<0.05), and positive surgical margins (OR 0.28 [95% CI 0.08-0.95]; p<0.05) were negatively associated with 100% necrosis.</p> <p><br>Conclusion and Implications:<br>A cutoff of 100% tumor necrosis was associated with improved survival in Ewing sarcoma. This association was strong relative to other commonly used prognostic factors in osseous cases and is a valuable tool to counsel patients and guide future clinical trials.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Matthew Marley, Christopher Collier, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27729TRIM31: A Protein With an Oncogenic Role in Esophageal Adenocarcinoma2023-12-06T12:51:03-05:00Jesse MastMd Sazzad HassanAnnie RitterAkashdeep SinghUrs von Holzen<p>Background: Esophageal adenocarcinoma (EAC) is a major cancer in the United States with increasing incidence. It is an aggressive cancer involving columnar-type cells different from the normal esophageal (NE) squamous cells. This metaplasia often involves an intermediary morphology called Barrett’s esophagus (BE), which occurs from repeated acid exposure of the esophagus from gastroesophageal reflux disease (GERD). GERD leading to BE is a common pre-occurrence in EAC patients, but the mechanism remains obscure. To explore the mechanism and its components, we compared gene expression in BE and EAC cells with normal cells and discovered the overexpression of TRIM31 in the pathogenic cells. Although previous studies have shown oncogenic potential of TRIM31 in some cancers, its role in EAC is yet to be understood.</p> <p><br>Methods: RNA sequencing and transcriptomic profiling were performed on human NE, BE, and EAC epithelial tissue samples. TRIM31 expression in NE cell line (Het-1A) and EAC cell lines (OE19, Flo-1, OE33, SK-GT-2, and OACM5.1C) were identified by Western blot. The Het-1A cell line, after exposure to acidic pH and bile acid, was assessed for variable TRIM31 expression. Cell viability analysis of NE and EAC cell lines after exposure to acidic pH and bile acids was observed by WST-1 assay.</p> <p><br>Results: RNA sequencing, transcriptomic profiling, and western blot revealed overexpression of TRIM31 in BE and EAC epithelium. Exposure of Het-1A cells to bile acids in acidic pH changed the cell morphology with enhanced expression of TRIM31. WST-1 revealed that EAC cells were more resistant to acidic pH and bile acid exposure.</p> <p><br>Conclusions and potential impact: Our data suggests that increased TRIM31 expression correlates with esophageal epithelium resistance when exposed to bile acids and acidic pH. Consequently, TRIM31 may be a key player in the metaplasia of GERD-induced EAC development and may be an innovative therapeutic target and marker for EAC.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Jesse Mast, Md Sazzad Hassan, Annie Ritter, Akashdeep Singh, Urs von Holzen, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27730Pharmacological Inhibition of PAK1 for the Treatment of NF2-Associated Vestibular Schwannoma2023-12-06T13:03:08-05:00Emma C. MazurekDana MitchellEric HawleySteve AngusD. Wade ClappCharles Yates<p>Neurofibromatosis Type 2 (NF2) is an autosomal-dominant genetic disorder characterized by loss of Merlin, a tumor suppressor in Schwann cells, resulting in pathognomonic bilateral vestibular schwannoma, among other complications. Depletion of Merlin results in pathologic elevation of p21-activated kinase 1 (PAK1), which promotes tumor cell proliferation, survival, and motility. Previous studies investigating the Nf2<sup>flox/flox</sup>; PAK1<sup>-/-</sup>; Postn-Cre+ genetically engineered mouse model (GEMM) revealed that PAK1 genetic knockout in Nf2-cKO mice mitigated tumor size and preserved hearing. This study builds upon this previous work to identify efficacious therapeutic agents that target PAK1. <em>In vitro</em> dose response curves evaluated the efficacy of five PAK inhibitors in merlin-deficient immortalized Schwann cells (MS03). Dose response curves revealed variable IC50s among the five PAK inhibitors tested. Synergy screens<br>revealed synergy between PAK inhibitors NVS-PAK1-1 or BGJ-398 and selumetinib, a MEK inhibitor FDA-approved for the treatment of NF1. Colony formation assays revealed robust inhibition with NVS-PAK1-1 in combination with VS6766, a RAF/MEK inhibitor currently being evaluated in clinical trial in other cancers. Western blot analysis revealed marked decrease in downstream effectors of PAK1, including phospho-ERK1/2 in cells treated with BGJ-398, NVSPAK1-1, and PAKi plus selumetinib. Together, these findings suggest that inhibition of PAK1 and MEK pathways may be an efficacious therapeutic strategy for the treatment of NF2- associated vestibular schwannoma. Establishing reproducibility of these results in cells derived from human vestibular schwannoma is necessary to continue investigating pharmacological PAK1 and MEK inhibition. Further studies are needed to verify tolerability and therapeutic<br>efficacy of PAK1 and MEK pharmacological inhibition <em>in vivo</em>.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Emma C. Mazurek, Dana Mitchell, Eric Hawley, Steve Angus, D. Wade Clapp, Charles Yates, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27731Clinical Markers for Small Vessel Pathology in Alzheimer’s Disease2023-12-06T13:18:51-05:00Quinn McBrideKwangsik NhoShannon L. RisacherAndrew J. Saykin<p>Background:<br>White matter hyperintensities (WMH) and cerebral microhemorrhages (MH) are common small vessel pathologies that often co-occur with hallmarks of Alzheimer’s Disease (AD) including amyloid-β and tau deposition, neurodegeneration, and decreased cognition. We investigated the relationship among these pathologies to better understand their roles in AD pathogenesis.</p> <p><br>Methods:<br>A sample from the AD Neuroimaging Initiative (ADNI) with baseline WMH volume WMHV), MH counts, and serum lipids measurements using the Nightingale Health metabolomics platform included cognitively normal, mild cognitive impairment, and AD participants. Spearman rank correlations coefficient and rank regression models were generated to assess the relationship between vascular pathology and mean arterial pressure (MAP), history of hypertension, and serum biomarkers. Models were covaried for age, sex, APOE status, BMI, and years of education. Further analysis was conducted by dividing participants based on APOE status. False discovery rate was controlled by the Benjamini-Hochberg method.</p> <p><br>Results:<br>WMHV and MH were weakly positively associated (ρ=0.197, p<1*10<sup>-10</sup>). MH and MAP were positively correlated (p<.05), but MH was not related to history of hypertension, or serum lipids. WMHV was negatively associated with serum VLDL cholesterol (p<1*10<sup>-12</sup>), LDL cholesterol (p<.0001), and remnant cholesterol (p<1*10<sup>-11</sup>). In APOE4 carriers only, WMHV was negatively associated with triglycerides (p<.001) and total fatty acids (p<.001), and positively associated with HDL cholesterol (p<.002). WMHV was not related to MAP or history of hypertension.</p> <p>Conclusion:<br>Vascular imaging markers have distinct risk factors with lipid profiles most associated with WMH burden, whereas MAP was predictive of MH. Counterintuitively, lipids associated with higher risk of systemic vascular pathology appeared protective against WMH in the ADNI sample. This phenomenon was particularly notable in APOE4 carriers. Further investigation should be conducted to better understand the relationship between serum lipids and small vessel pathology, and how these contribute to AD pathogenesis.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Quinn McBride, Kwangsik Nho, Shannon L. Risacher, Andrew J. Saykin, PsyDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27732Analysis of Nutritional Composition and Glycemic Control in Patients with Gestational Diabetes Mellitus2023-12-06T13:32:54-05:00Evelyn McGuireBrenda SmithChristina Scifres<p>Background:<br>The association between meal content and glycemic control is not well-understood in pregnancy, limits our ability to counsel patients regarding the optimal diet. We therefore sought to evaluate the relationship between maternal dietary content and glycemic control.</p> <p>Methods:<br>This is a secondary analysis of the GDM-MOMS study, which was a randomized controlled pilot trial that compared glycemic targets in 60 pregnant individuals with GDM and either overweight or obesity. During the pilot trial, participants wore a blinded continuous glucose monitor (CGM) for two five-day periods, with the first data collection between 12-32 weeks and the second data collection between 32-36 weeks. During the time that participants wore their CGM, they also collected 3-day food diaries with detailed information regarding intake and cooking technique. These food diaries are being entered into the Nutrition Data System for Research (NDSR) software, which analyzes nutritional composition for each meal. Glycemic control as assessed by CGM will then be assessed based on maternal nutritional intake.</p> <p>Results:<br>The American Diabetes Association recommends a 2,000-calorie daily diet with a minimum of 175g of carbohydrates (with 35% of the total calories coming from carbohydrates), 71g of protein, and 28g of fat. Preliminary data extracted from NDSR includes nutritional analysis of 38 daily food diaries from 14 patients. 12/38 (31.6%) food logs show consumption of less than 35% of their total calories from carbohydrates, with the other 26 consuming 36-62%. Glycemic load can be used to assess how a patient’s diet affects their glycemic levels. 25/38 (65.8%) of food logs demonstrate a daily glycemic load (GL) of 100, with the other 13 showing daily GLs ranging<br>from 108-252.</p> <p>Conclusions and Further Directions:<br>Further analyses will assess post-meal glycemic response using both patient-monitored glucose values and reports from their CGM to determine which types of diets allow for optimal glycemic control.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Evelyn McGuire, Brenda Smith, Christina Scifres, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27733Antifungal Activity of a Wireless Electroceutical Dressing2023-12-06T13:43:50-05:00Josey McKinleyNese Basaran-AkgulShomita S. SteinerChandan K. SenSteven P. Templeton<p>Background:<br><em>Fusarium</em> and <em>Mucor</em> are two filamentous fungus strains that can cause infections in humans. <em>Fusarium</em> is known for causing corneal infections. Patients who have diabetes mellitus or are immunocompromised are at a higher risk of mucormycosis. Wireless electroceutical dressing (WED) contains embedded silver and zinc nanoparticles in a geometric pattern. Both zinc and silver have been known to be antimicrobial; yet the combination results in a weak electric field when exposed to an electrolyte-containing solution. WED has been found to have antifungal effects against <em>Candida albicans</em> and <em>Aspergillus fumigatus</em>.</p> <p>Methods:<br>We investigated the antifungal effect of WED against <em>Fusarium</em> and <em>Mucor</em> growth and survival through daily radial growth and optic density readings.</p> <p>Results:<br>Our results show that the WED weakly inhibits radial growth of <em>Fusarium</em> strains and strongly inhibits radial growth of Mucor strains, with greater inhibition near physiologic temperatures. Although zinc and silver-only fabric inhibited the radial growth of <em>Mucor</em>, no growth occurred on WED (Ag-Zn) plates for <em>Mucor</em> strains. Optic density readings had mixed results; Ag-Zn liquid cultures had reduced absorbance than control cultures for both strains. Zone of inhibition studies of Fusarium showed no growth on Ag-Zn fabrics with full coverage on all other control and metal containing plates. WED had a greater effect on reducing <em>Mucor</em> growth than <em>Fusarium</em>.</p> <p>Conclusions:<br>WED utilizes a weak electrical field created by silver and zinc nanoparticles to create an antifungal effect. This leads to strong inhibition of <em>Mucor</em>, <em>Candida</em>, and <em>Aspergillus</em> growth and weak inhibition of <em>Fusarium</em> growth. Further studies are needed to determine the specific effect of WED on fungal viability, the mechanism, and <em>in vivo</em> efficacy. This work could increase patient treatment options for fungal wound infections.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Josey McKinley, Nese Basaran-Akgul, Shomita S. Steiner, Chandan K. Sen, Steven P. Templeton, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27734Suppression of Inflammation-induced Abdominal Aortic Aneurysm Formation by Induction of Elastin Tolerance2023-12-06T13:50:42-05:00Stone ChenTheresa DoironOlivia JimenezAli SualehJennifer StashevskyMackenzie MadisonChang-Hyundai GilSteven MillerMichael Murphy<p>Abdominal aortic aneurysm (AAA) is a vascular disease process whereby the aorta expands to apoint where rupture may occur. This serious condition is diagnosed in approximately 200,000 people in the United States per year and accounts for over 15,000 deaths annually. The only medical intervention proven to reduce the risk of AAA rupture is surgical repair; however, such repair is associated with high risk of death, reduced quality of life, and high expense. AAA is caused by the weakening of the artery wall due to inflammation-induced destruction of its structural components. Our clinical data shows increased levels of circulating elastin degradation products in patients with AAA, especially smokers, compared to risk factor matched controls. This observation led us to hypothesize that an immune reaction to elastin fragments initiates the inflammatory cascade in the aorta that leads to AAA formation. To test this hypothesis, C57BL/6 mice were injected with poly(lactide-co-glycolide) nanoparticle-encapsulated IL-10 to induce immune tolerance or nanoparticle-encapsulated control ovalbumin. Injection of elastin fragments was performed 7 days later to induce an immune response. AAA of the infrarenal aorta was induced by topical application of elastase during laparotomy procedure 14 days after nanoparticle injection. Aorta diameter was measured 16 days post-operatively with Microfil. Immunologic changes were evaluated by cytokine analysis, Tr1/Th17 cell ratio inperipheral blood, and splenic Th17 and Tr1 response to elastin. Based on prior work, we expect that induction of elastin tolerance using poly(lactide-co-glycolide) nanoparticle-encapsulated IL-10 will suppress abdominal aortic aneurysm expansion and promote an anti-inflammatoryenvironment characterized by increased Tr1/Th17 cell ratio, increased levels of anti-inflammatory cytokines, and decreased pro-inflammatory cytokine expression.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Stone Chen, Theresa Doiron, Olivia Jimenez, Ali Sualeh, Jennifer Stashevsky, Mackenzie Madison, Chang-Hyundai Gil, Steven Miller, Michael Murphyhttps://journals.iupui.edu/index.php/IMPRS/article/view/27735Affinity Purification of Anti-Parkin Antibodies from Rabbit Serum for their Application in Immunohistochemistry2023-12-06T13:58:46-05:00Noah McMurtryBo Zhao<p>Background:<br>Parkin is a mitochondrial autophagy protein that is associated with Parkinson’s Disease (PD), as well as auditory function. Parkin dysfunction in the context of PD allows accumulation of protein aggregates, leading to dopaminergic neurotoxicity. Previous work has demonstrated that Parkin plays an essential role in normal auditory function, as <em>Prkn<sup>-/-</sup></em> mice exhibit significantly reduced hearing sensitivity. However, <em>Prkn<sup>-/-</sup></em> mice also experience a protective effect from cochlear hair cell death and hearing loss caused by aminoglycosides, which are commonly used antibiotics that can cause permanent hearing loss. Multiple antibodies marketed as suitable for immunohistochemistry (IHC) have been validated using <em>Prkn<sup>-/-</sup></em> tissues; however, they exhibit non-specific activity. This project aims to generate a highly specific antibody for accurate and reliable detection of Parkin expression.</p> <p>Project Methods:<br>Rabbits were immunized using two Parkin peptides, notated P1 and P2, and the resulting serum was collected. A two-step purification process was utilized in this project, first isolating the IgGs from serum via protein A/G columns, and secondly using affinity purification to obtain specific antibodies against antigens P1 and P2. Additionally, two different protocols for affinity purification were tested and compared. Purity of serum, IgG, and specific antibodies was assessed by Western blot and immunofluorescence.</p> <p><br>Results:<br>Utilizing the first purification protocol, IHC antibodies were applied in Western blot, and all demonstrated a prominent ~50kD band specific to Parkin, with some degree of nonspecific binding. Immunostaining confirmed functionality of the IHC antibodies and revealed those against P2 exhibited higher binding specificity. The second purification protocol generated IHC antibodies of similar, if not slightly superior specific interaction.</p> <p>Conclusion/Implications:<br>Further investigation of Parkin expression would facilitate a better understanding of how it may be associated with the development of PD, as well as auditory function, with the potential of utilizing Parkin as a therapeutic target in PD treatment and preventing aminoglycoside ototoxicity.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Noah McMurtry, Bo Zhao, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27736Changes in Address and the Child Opportunity Index after Delivery in a Cohort of First-time Mothers2023-12-06T14:12:07-05:00Katherine ModrallAlexander YusmanDavid GuiseOlivia AbrahamAlekhya JampaSara QuinneyDavid Haas<p>Background: The Child Opportunity Index (COI) characterizes social determinants of health across the United States including education, health and environment, and social and economic factors. The objective of the study was to determine if the nulliparous pregnant persons changed addresses between the time of delivery and at the time of follow-up 9-11 years after delivery and to evaluate the trajectory of the COI over time.</p> <p>Methods: We analyzed data from nulliparous pregnant people participating in the nuMoM2b Heart Health follow-up Study (HHS). Residential addresses at delivery and at follow-up (~9 years) were compared to determine if the participant changed addresses and to evaluate the COI trajectory. Descriptive characteristics (age, race, income, pregnancy outcomes) and the COI trajectory were compared for those who did and did not move using chi-square and t-tests.</p> <p>Results: 410 participants were analyzed. 304 (74%) of the participants changed addresses resulting in changes in census tracts. Moving was associated with a lower mean maternal age (24.3 vs. 27.2 yrs, p≤0.001) and a lower average income (62.3% vs 41.1% <200% FPL,<br>p≤0.001) compared to the participants who did not move. 40.5% moved to a neighborhood with a higher COI quintile, 56 (18.4%) participants moved down a COI quintile, and 125 (41.1%) participants did not have a change in COI category. White participants who moved addresses were significantly more likely to increase their COI category (55%) compared to non-White participants who moved addresses (22.2%, p≤0.001). There were no differences in how COI changed between White and non-White participants who did not move.</p> <p><br>Conclusion: The majority of the participants moved in the years after delivering their first child. Moving was typically associated with an improvement in COI categories, with disparities seen as White participants were more likely to increase their COI if they moved compared to non-White groups.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Katherine Modrall, Alexander Yusman, David Guise, Olivia Abraham, Alekhya Jampa, Sara Quinney, David Haas, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27737Therapeutic Effects of a Placental Tissue-Derived Allograft on Fracture Healing2023-12-06T14:24:41-05:00Ashlyn MorrisUpasana GangulyTyler MargettsWill VarnerAamir TuckerAlexander HarrisMurad NazzalReginald ParkerHannah WangSonali KarnikRachel BlosserIstvan GergelyNatalie NguyenFletcher WhiteJill FehrenbacherMelissa Kacena<p>Background:<br>As 5-10% of fractures will not heal without medical intervention, there is an ongoing need for effective treatments to promote fracture healing. CTM Biomedical produces human placental tissue-derived allografts that are used clinically and may assist in healing; however, no pre-clinical studies assessing these products have been performed. Our study investigating the impact of CTM products on the healing of a standard femoral fracture and a critical sized femoral defect (CSD) aims to fill this gap. We hypothesize that CTM product application will improve fracture healing and reduce pain-related behaviors.</p> <p>Methods:<br>Femoral fractures were induced in 45 mice. CTM membrane, CTM paste, a combination of CTM membrane and paste, or saline was applied to each fracture. X-rays were taken twice weekly over 22 days, and blinded modified Radiological Union Scale for Tibia (mRUST) fracture scoring was performed. Complete blood analysis was conducted weekly. Following euthanasia 23 days post-surgery, μCT and histomorphometric analyses were conducted. CSDs have also been surgically induced in the femurs of 95 mice, with plans for similar fracture analyses.</p> <p>Results:<br>CTM product application did not significantly alter the levels of inflammatory cells, suggesting that the mice did not undergo immunological reactions. mRUST scoring indicated that CTM products may not alter fracture healing rates. However, combined application of CTM membrane and paste significantly increased the fracture callus’s mineralized volume (by ~90%) and the percent of the callus that was bone. CTM membrane and paste application also led to an increased threshold for hind paw withdrawal, suggesting that CTM products may decrease pain-related behaviors.</p> <p>Future Directions:<br>We hypothesize that in our CSD model, mice treated with the combination of CTM membrane and paste will display improved fracture healing and decreased pain-related behaviors. If shown to be effective, CTM product use may decrease fracture nonunion risk and increase comfort.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Ashlyn Morris, Upasana Ganguly, Tyler Margetts, Will Varner, Aamir Tucker, Alexander Harris, Murad Nazzal, Reginald Parker, Hannah Wang, Sonali Karnik, Rachel Blosser, Istvan Gergely, Natalie Nguyen, Fletcher White, Jill Fehrenbacher, Melissa Kacena, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27739Characterization of the Function of Carbonic Anhydrase 82023-12-06T14:40:05-05:00Jenny ChenLaura SmithBenjamin Gaston<p><strong>Background/Objective:</strong> Severe asthma is a complex pulmonary disease characterized by airway inflammation, bronchoconstriction, and acid-base dysregulation. In the Severe Asthma Research Program bronchoscopies, transcriptomics showed CA8 as a gene that is strongly associated with asthma severity. CA8, however, lacks classical CA enzyme function: it does not catalyze hydration and dehydration of CO2. The function of CA8 in the airway epithelium remains unknown. We hypothesize that CA8 serves a protective role in the airway due to its down regulation in patients with severe asthma. We aim to characterize the function of CA8 bystudying its potential as an enzymatic protein.</p> <p><strong>Methods:</strong> We used colorimetric assays to detect and quantify nitrogen oxides. We tested for Snitrosothiolsynthase, denitrosylase, nitrate and nitrite synthase, and nitrite reductase activitiesusing the Griess reagent in conjunction with Saville denitrosylation reagents and with reduction using vanadium chloride. Samples were incubated for 60 minutes. We then went on to design ametabolomic experiment in which products will be identified by NMR: for these, we transfected Chinese hamster ovary (CHO) cells using lentivirus containing GFP-labeled CA8 or emptyvector (negative control).</p> <p><strong>Results:</strong> CA8 protein does not have these following enzymatic functions: SNO synthase,denitrosylase, nitrite and nitrate synthase, and nitrite reductase. We successfully transfected with GFP-labeled CA8 and are awaiting results of the metabolomic studies.</p> <p><strong>Conclusion and Potential Impact:</strong> Isolated CA8 does not appear to have any nitrogen oxideredox activities relevant to asthma. The next steps include confirmatory western and SNOwestern blots to determine protein s-nitrosylation using transfected CHO whole cell lysate. Extracellular medium pH will also be measured. We will then move on to NMR-basedmetabolomics. This will help us better understand the biochemical mechanisms of CA8.Ultimately, this can provide researchers with a novel approach to asthma treatments.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Jenny Chen, Laura Smith, Benjamin Gastonhttps://journals.iupui.edu/index.php/IMPRS/article/view/27740Assessment of Patient Referrals with Large Numbers of Non-pedunculated Colorectal Lesions2023-12-06T15:05:13-05:00William ChengDouglas Rex<p><strong>Background:</strong> Large (≥20mm) non-pedunculated colorectal lesions are frequently referred to specialty centers for endoscopic resection. These lesions are technically challenging to resectand associated with substantially greater risk than smaller lesions. Patients with such polypsoften have synchronous lesions. We sought to identify evidence for whether synchronouslesions were sometimes the true basis for referral of large non-pedunculated colorectal polypsfrom community endoscopists to a tertiary center.</p> <p><strong>Methods:</strong> We utilized a prospectively collected database of 1356 consecutive referred patients to an expert colonoscopist at our tertiary center between August 2019 and May 2023. We identified patients with ≥30 precancerous lesions resected from the colorectum during their first two colonoscopies at our center. Patients in the database with the same gender, within 3 yearsof age, and with the same location (proximal vs. distal colon) of the index large lesion referred for resection were identified as controls. Groups were compared for the size of index lesion, number of polyps resected by both centers, and size of polyps resected.</p> <p><strong>Results:</strong> Among 1356 patients, 49 (3.6%) had ≥30 precancerous lesions resected at our center. Compared to controls, the index lesion was smaller in patients with ≥30 lesions (mean 28.9mmvs 23.3mm). Among patients with ≥30 synchronous polyps, the referring physician resected 10.6% of all synchronous lesions, compared to 47.8% in the control group (p<0.0001). Inpatients with ≥30 lesions, 84% of all synchronous lesions were <10mm, 15% were 10-19mm, and only 1% were >20mm.</p> <p><strong>Conclusion:</strong> Our results suggest a subset of patients with large non-pedunculated colorectal precancerous lesions referred to tertiary centers are referred because of the number of lesions present, rather than technical challenges associated with resection of individual lesions. The rationale for these referrals is uncertain. It may lie in the reimbursement system, which only compensates physicians for the first polypectomy.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 William Cheng, Douglas Rex, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27741Factors Contributing to Potentially Unnecessary Pediatric Emergency Transfers2023-12-06T15:28:33-05:00Kortni ClementsNancy Glober<p><strong>Background:</strong> Riley Hospital for Children receives thousands of emergency pediatric transfers from outside hospitals every year. The United States is currently facing a national EMS shortage along with increasing costs of medical care. Additionally, these transfers can be inconvenient for patients and their families. However, not all of these transfers are medically necessary. Identifying factors that contribute to unnecessary emergency transfers is essential for optimizing care for each patient.</p> <p><strong>Methods:</strong> Retrospective chart reviews of electronic medical records at Riley Hospital for Children were completed for transferred patients between 01/01/2022 to 02/20/2022. Patients were identified through the transfer center patient list. The primary objective of the study was to identify patients transferred and discharged from the emergency department without advanced imaging or specialist consult. Demographic data including age, race, ethnicity, and sex were collected.</p> <p><strong>Results:</strong> There were 404 patients included in the study. About one third of these patients were discharged from the emergency department. Of those, 38 patients (9.4%) also did not have advanced imaging or a specialist consult in the Riley Emergency Department. Age was found to<br>be statistically different between these patients and all other patients. The median age for patients discharged without advanced imaging or specialist consult was 2.4 years old, while the median age for all other patients was 6.5 years old. Other demographics including race, ethnicity, and sex were not significantly different.</p> <p><strong>Conclusion and Potential Impact:</strong> The results suggest that younger pediatric patients may be at a greater risk for unnecessary emergency transfer. The generalizability of this study is limited in scope due to the use of only one EMR and hospital system. Finally, as this is a retrospective study, the information is limited by what was documented.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Kortni Clements, Nancy Glober, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27742Preliminary Assessment of Cognitive Changes in Pediatric Cancer Survivors After a Neurocognitive Intervention2023-12-06T15:37:27-05:00Maddie ClemmerDonna RomackScott CovenSarah KochTammy Sajdyk<p><strong>Background:</strong> Pediatric patients with acute lymphoblastic leukemia (ALL) receive large doses of neurotoxic chemotherapy as part of their treatment. Though lifesaving, it can induce life-long issues. Cognitive deficits are one of the most common reported concerns in survivorship clinic among pediatric cancer survivors. One unique approach to improving deficits in cognitive functioning is The Mediated Learning Experience (MLE) developed by Reuven Feuerstein. MLE is based on neuronal plasticity. Findings from MLE studies have shown improvements in cognitive task performance, increases in daily functioning, and increased learning in patients with neurological impairment. However, MLE has never been administered to children or adolescent cancer survivors with cognitive deficits.</p> <p><strong>Methods:</strong> Survivors were recruited from the Survivor Clinic in IU North Hospital. Survivors were 10-16 years of age, English speaking, and reporting executive functioning issues in school. The intervention utilized was the MLE enrichment tool: Organization of Dots. Participants met with MLE certified mediators 30 – 40 minutes biweekly for 8 weeks. At 5 weeks, separate interviews were conducted with parents and participants to assess perceived changes in cognitive functions. These interviews asked participants to rate perceived changes on a Likert-type scale, which allowed for comparison of perceived changes reported by participants and parents.</p> <p><strong>Results:</strong> Four participants and their parents completed the 5-week interview. Preliminary results show participants and their parents perceive positive changes in the participants’ cognitive skills, new learning, motivation, transfer, metacognition, and active learning.</p> <p><strong>Conclusion/Potential Impact:</strong> Many pediatric cancer survivors experience cognitive deficits following their cancer treatment. There are limited options for these individuals for assistance in improving function, most of which are costly or difficult to access. The current study demonstrated that utilization of the MLE approach by Feuerstein can be a feasible option for filling the resource gap in neurocognitive rehabilitation.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Maddie Clemmer, Donna Romack, Scott Coven, Sarah Koch, Tammy Sajdyk, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27744Delayed Prescribing of Non-Vitamin K Antagonist Oral Anticoagulants (NOACs) in Patients with Low Socioeconomic Status2023-12-06T15:56:19-05:00Gillian CoffeyPuja UnniJames Butler<p><strong>Background/Objective:</strong> Atrial fibrillation (AF) and venous thromboembolism (VTE) are conditions with significant morbidity and mortality when left untreated. American Heart Association guidelines changed in 2019 to make non-vitamin K antagonist oral anticoagulants (NOACs) the preferred method for preventing stroke and systemic embolism in patients with AF or history of VTE. NOACs were first introduced to the United States in 2010 and now include dabigatran, apixaban, rivaroxaban, and edoxaban. There is a dearth of research concerning the speed with which new treatments are prescribed to those in different socioeconomic status (SES) groups. We hypothesized that patients with lower SES were prescribed NOACs later than higher SES counterparts following the introduction of NOACs in 2010.</p> <p><strong>Methods:</strong> The IU Cardiovascular Research Consortium/Sidus Dataset was mined for AF and VTE patients prescribed a NOAC between 2010 and 2022. The SES groups were determined using 2020 U.S. Census income data that correlated to patients’ zip codes. The yearly number of<br>patients in each SES group were compared to assess for proportional uptake of NOAC prescribing. The primary outcome was the proportion of low SES to high SES prescribing over each year between 2010 and 2022.</p> <p><strong>Results:</strong> Low SES patients (n=101,945) were prescribed NOACs at an average of 0.65 times the rate of high SES patients (n= 89,130) from 2010 to 2012, the first three years of NOAC market availability. Prescribing rates equilibrated in 2013 and low SES prescribing has outpaced high SES prescribing since 2021.</p> <p><strong>Conclusion/Impact:</strong> Low SES patients experienced a three year delay in receiving NOAC prescriptions at the same rate as their high SES counterparts. Systemic changes, like more frequent prescribing guideline updates and improved evidence-based education amongst providers in low-income areas, could prevent a similar delay when introducing similarly transformative treatments in the future.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Gillian Coffey, Puja Unni, James Butler, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27745Analysis of Lung Cancer Disparities in Northwest Indiana2023-12-06T16:15:03-05:00Kyra ColstonMia NdamaAmy Han<p><strong>Background and Hypothesis: </strong>Lung cancer is the first leading cause of cancer death worldwide (~1.8 million deaths pa.). Low-Dose Computed Tomography (LDCT) screening is a preventative measure to diagnose lung cancer at an early stage, which increases the chance of survival. Northwest Indiana is a diverse region (830,000 pop.) that faces unique challenges to equitable health outcomes and access to preventative treatments, particularly within minoritized communities from a low socioeconomic status. We investigated whether the vulnerable populations of Northwest Indiana have a higher incidence of lung cancer, low LDCT screening rates, and a late stage of diagnosis, in order to identify potential gaps in healthcare access and delivery.</p> <p><strong>Methods: </strong>We used LDCT screening (n = 2,481), lung cancer incidence (n = 268) and staging (n = 257) data from ZIP Codes of six cities/towns in Northwest Indiana, provided by an urban hospital system in Northwest Indiana between 2018 and 2023. The cities/towns were grouped into ‘lower’ and ‘upper’ income according to median household income level reported by 2020 U.S. census data. Chi-Squared tests were used to determine significance.</p> <p><strong>Results: </strong>There is no significant difference in the incidence of lung cancer between upper and lower income cities/towns (p= 0.163). However, there is a significant difference in stage I, II, and IV diagnoses between the two income groups (p = 0.021, 0.007, and 0.013 respectively), which demonstrates an inverse relationship between income level and stage of diagnosis. The lower income group is diagnosed at a younger age (p = 0.02) with advanced stage lung cancer, despite similar rates of lung cancer incidence.</p> <p><strong>Conclusion and Potential Impact: </strong>Barriers to screening for vulnerable populations in urban areas include patient-provider mistrust, health illiteracy, and lack of healthcare services. Late stage diagnosis necessitates the development of local interventions to increase early screening.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Kyra Colston, Mia Ndama, Amy Han, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27747Clinical Applications of Next-Generation Sequencing for Cancer Diagnostics and Targeted Cancer Therapy2023-12-07T05:07:14-05:00Alex MostellerAshiq Masood<p>Next-generation sequencing (NGS) is a revolutionary technology that has effectively sequence massive quantities of genomic DNA or RNA at a shorter time and a lower cost. The NGS is routinely used in oncology to tailor care for individual patient. In this review, we discuss the role of NGS how it can provide a more personalized approach to targeted cancer therapy. A literature review was conducted via PubMed and articles were screened for publication dates within the past 10 years. Primary literature consisting of clinical trials and review articles were utilized. Search terms included “(next-generation sequencing) AND (cancer)”, “(next-generation sequencing) AND (cancer diagnostics)”, and “(next-generation sequencing) AND “(cancer therapy)”.</p> <p>From the literature review, we found that NGS is indicated for daily practice as a diagnostic tool for advanced NSCLC, colon cancer, prostate cancer, cholangiocarcinoma, and some advanced rare cancers. We also found evidence suggesting that NGS is helpful in identifying actionable mutations that will, in turn, allow the patient to be matched to a more individualized cancer treatment.</p> <p>As oncology care continues to move in the direction of more personalized care, the potential applications of NGS in the field of oncology will continue to evolve. Our review will help further the understanding of NGS and provide context for its value in patient care and its ability to provide an avenue for targeted therapy.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Alex Mosteller, Ashiq Masood, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27748Deciphering the Immune Microenvironment of NF1-associated Peripheral Nerve Sheath Tumors: Identifying Early Biomarkers of Disease Progression and Malignant Transformation2023-12-07T05:18:02-05:00Janak MukherjiDana MitchellEmily WhiteBreanne BurgessAbbi SmithEric AlbrightJaffar KhanAndrew HorvaiD. Wade ClappSteve AngusSteven Rhodes<p>Background/Objective:<br>Neurofibromatosis type 1 (NF1) is a multisystem disorder that affects ~1/3000 newborns. Plexiform neurofibromas (PN) are present in about half of cases and can transform (lifetime risk of 8-13%) into malignant peripheral nerve sheath tumor (MPNST), a highly aggressive and metastatic sarcoma with poor survival. Unfortunately, there are currently no reliable biomarkers to identify PN at risk of undergoing malignant transformation. Our research has revealed that a subset of benign-appearing and atypical PN exhibit deregulated immune surveillance and T-cell infiltration that precede malignant transformation. In this study, we are analyzing tumor microenvironment and immune landscape in NF1-related tissue specimens to identify biomarkers of disease progression. To power these studies, this project focused on constructing a dataset of NF1-related samples to be analyzed.</p> <p>Methods:<br>701 patients were identified via Cerner billing codes and pathology archives. De-identified clinical data, including presenting symptoms, relevant clinical history, pathology diagnoses, disease features, prior chemotherapeutics/radiation, prior gene profiling, and imaging features were collected.</p> <p>Results: We selected 86 patients with a total of 175 samples. 81% of patients had a clinical diagnosis of NF1, and 6% had a history of MPNST. Out of the 175 samples, 54 were in the head and neck, 42 in the thorax, 28 in the lower extremity, 27 in the upper extremity, 26 in the pelvis/abdomen, and 15 in the paraspinal region. The leading causes of procedures were pain (41%), growth (40%), and concern for malignancy (27%). The most common tissue diagnoses were neurofibroma (51.4%), PN (20%), and undefined-grade MPNST (11%). Out of the 46 MPNSTs, 30 were primary tumors, 4 metastases, and 12 local recurrences.</p> <p>Conclusion and Potential Impact:<br>The results of this study will provide valuable insights to inform preclinical models of NF1-tumorigenesis to validate these findings and identify novel treatment approaches for individuals affected by these rare but devastating tumors.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Janak Mukherji, Dana Mitchell, Emily White, Breanne Burgess, Abbi Smith, Eric Albright, Jaffar Khan, Andrew Horvai, D. Wade Clapp, Steve Angus, Steven Rhodes, MD, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27749Hypoxia Gene Networks in Gliomas2023-12-07T05:43:48-05:00John MullerLuke JacksonElise O’HerronScott CooperAngela Richardson<p>Background and Hypothesis:<br>Gliomas are the most common primary brain tumor and range from low grade to high grade, with glioblastomas (GBM) being the most aggressive. Translation of therapies for these tumors from preclinical models to clinical practice has been limited. Preclinical studies are typically performed in ambient air (21% oxygen), while physiological oxygen tension (physioxia) is 3-5%. Extracranial tumor tissue processed in physioxia demonstrates distinct gene expression profiles and chemoresistance as compared to the same samples processed in ambient air. However, the role of varying oxygen tension in gliomas has not been well studied. GBMs often have areas<br>of necrosis with presumed low oxygen tension, while these findings are typically absent in lower grade gliomas. In this study, we examine expression of hypoxia related genes in patient samples obtained from grade II, III and IV gliomas. We hypothesize that increasing tumor grade will be associated with differential expression of hypoxia-related genes.</p> <p>Methods:<br>Gene expression in patient brain tumor samples (glioblastoma, high grade astrocytoma, low grade astrocytoma) and normal brain samples (from epilepsy surgery) was assayed using real time PCR. Hypoxia-related gene expression was examined in cBioPortal for Cancer Genomics by comparing survival in the top-expressing and bottom-expressing quartile for these transcripts.</p> <p>Results:<br>Patient samples were screened for differences in gene expression with greater than two-fold upregulation in GBM as compared to normal brain tissue. Expression level of one of these genes, ADM, was significantly associated with survival in patients with GBM (p<0.05). Additional differences between grades of glioma will also be presented.</p> <p>Potential Impact:<br>This work demonstrates differential expression of hypoxia-related gene transcripts in gliomas. The next step is to assess differences between patient samples processed in differing oxygen tensions to assess efficacy of chemotherapeutics and gene expression in samples that have never been exposed to ambient air.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 John Muller, Luke Jackson, Elise O’Herron, Scott Cooper, Angela Richardson, MD, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27750The Effects of Age and Sex of Megakaryocyte Secreted Factors on Endothelial Cell Growth and Function2023-12-07T06:13:49-05:00Murad K. NazzalHanisha L. BattinaNikhil P. TewariSarah L. MostardoRohit U. NagarajOlatundun D. AwosanyaSaveda K. MajetyAnthony C. McGuireSue SamsonRachel J. BlosserUshashi C. DadwalSafa F. MohamadEdward F. SrourAngela BruzzanitiMelissa A. Kacena<p>With an aging population, the risk of fractures and compromised healing increases. Angiogenesis and vasculogenesis are impaired with aging. Vascularization at the callus plays a significant role in bone healing, and we have previously shown the important role of<br>megakaryocytes (MKs) in regulating bone healing. Notably, MK-derived conditioned media (CM) contains factors known to promote angiogenesis. Whether differences exist with aging and/or based on sex was the primary focus of this study. Here, we examined the effects of CM secreted from MKs derived from young (3-4-month-old) and aged (22-24-month-old) male and female C57BL/6J mice on bone marrow endothelial cell (BMEC) growth and function. Specifically, BMEC proliferation, vessel-like formation, wound/transwell migration, and RNA expression were examined. Both young and aged female MK CM saw a >65% increase in BMEC proliferation<br>(p<0.001 and p<0.05, respectively). In addition, female MK CM, regardless of age, improved all four parameters of vessel-like formation by >115% (p<0.05). Likewise, young male MK CM increased vessel-like formation in all parameters by more than 160% (p<0.001). Although aged male MK CM resulted in higher vessel-like formation parameters, including significant >150% increases in the formation of nodes and meshes, 62% fewer vessel-like structures formed compared to that observed with young male MK CM treatment (p<0.05). Additionally, aged MK CM, irrespective of sex, improved transwell migration by over 2500% (p<0.01). On the other hand, aged female and male MK CM inhibited wound closure by 46% and 17%, respectively (p<0.05). RNA analysis found MK CM yielded significantly different levels of expression in CXCR4, CXCR2, CD36, CD74, PDGFRB, and TGFBRB not only relative to controls, but also between sexes and ages. Further testing to identify the mechanisms responsible for these age-associated differences may allow for novel treatment strategies to improve MK-mediated angiogenesis, vasculogenesis, and bone healing, particularly within the aging population.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Murad K. Nazzal, Hanisha L. Battina, Nikhil P. Tewari, Sarah L. Mostardo, Rohit U. Nagaraj, Olatundun D. Awosanya, Saveda K. Majety, Anthony C. McGuire, Sue Samson, Rachel J. Blosser, Ushashi C. Dadwal, Safa F. Mohamad, Edward F. Srour, Angela Bruzzaniti, Melissa A. Kacena, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27752Heterozygous PAI-1 Deficiency’s Role in Pathological Aging in the Human Cardiovascular System2023-12-07T06:43:53-05:00Allison NelsonDouglas Vaughan<p>Background and Objective: Plasminogen activator inhibitor (PAI-1) is a member of the fibrinolytic system and a marker and a mediator of cellular senescence. Experimental evidence in humans suggests that higher levels of PAI-1 are associated with increased pathological aging in several major organ systems of the human body. To better understand the role of PAI-1 in humans, specifically in the cardiovascular system, we studied the effects of a loss-of-function mutation in SERPINE1, the gene encoding PAI-1, in an Old Order Amish community in Berne, Indiana. Overall, carriers of the null SERPINE1 variant had greater leukocyte telomere lengths, lower fasting insulin levels, and less prevalent diabetes mellitus. To further the conclusions previously published, our goal is to continue to analyze data collected alongside demographic data to determine if there is a link between PAI-1 deficiency and protection against aging-related changes in the human cardiovascular system. We hypothesized that the differences between the cardiovascular endpoints between carriers and non-carriers will be most significant in older groups.</p> <p>Methods: Participants included 177 members of the community, 43 of which were carriers for the SERPINE1 mutation. To test our hypothesis, we divided participants into tertiles and compared the results of selected cardiovascular parameters of those with and without the mutation in each tertile.</p> <p>Results: Our analysis revealed a statistically significant difference in brachial pulse pressures between carriers of the null mutation and normal individuals in the third tertile, corresponding to individuals ages 55 to 82. Those heterozygous for the mutation in this age group had a lower brachial pulse pressure, suggesting there are protective effects of PAI-1 haploinsufficiency against endothelial senescence as people age.</p> <p>Potential Impact: By identifying the age group with the most pronounced effects of PAI-1 deficiency, we can further investigate the means by which these results manifest in humans and better understand where in the aging process they are most significant.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Allison Nelson, Douglas Vaughan, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27753Intraoperative Cognitive Load Differences between Trainees and Attending Surgeons2023-12-07T07:08:45-05:00Alex NelsonNicholas AntonMohammed KalantarDimitrios Stefanidis<p>Background/Objective: Cognitive load (CL) is the amount of mental effort and resources required to complete a task and process information in the working memory. In a surgical setting, high CL decreases attention to critical details, and slows down decision-making, increasing errors which can compromise patient safety. Our aim was to determine if CL differences exist between trainees and experienced attending surgeons. Such differences could inform readiness for trainee autonomy and training paradigms.</p> <p>Methods: Eye trackers were used by attending general surgeons and trainees during robotic gastrointestinal procedures to determine their CL. Average fixation rate (AFR), fixation to saccade (F:S) ratio, and change in pupil size, were recorded and compared between attending surgeons and trainees to determine differences in intraoperative cognitive load.</p> <p>Results: Three attendings and three trainees participated. While operating, trainees had a lower AFR (M=0.775, SD= 0.093) and a lower F:S (M=0.497, SD=0.102) compared to attendings (M=0.842, SD=0.152 and M=0.592, SD=0.243, respectively). Both trainees and attendings had a larger pupil size (M=4.29, SD=0.773 and M=3.63, SD=0.077, respectively) while operating compared to their pupil size while not operating (M=4.057, SD=0.821 and M=3.496, SD=0.059, respectively.</p> <p>Conclusion and Potential Impact:<br>In this pilot study, we determined eye tracking metrics can be used to detect differences in intraoperative CL between trainees and attending surgeons and while they were operating or observing. Further research should determine methods that decrease CL of trainees.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Alex Nelson, Nicholas Anton, Mohammed Kalantar, Dimitrios Stefanidis, MD, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27754A Case Study on the Relationship Between a Multimodal Approach to Opioid Treatment and Opioid Cessation in Low-Income BIPOC Communities2023-12-07T07:18:33-05:00Adaobi OkolochaJasser Khairallah<p>Background and Hypothesis:<br>In the United States, the opioid crisis has been centered around white individuals in suburban and rural areas. However, communities of color who have a low socioeconomic status (SES) are facing an increasing amount of opioid overdose related deaths. Even with pharmacological opioid agonist therapy, this specific population still does not have the support to remain abstinent from opioids. We have conducted a case study with Mr.G, a 32 year old black male patient with opioid use disorder (OUD) who is from a low SES. Mr. G suffered from four overdoses over a six-month period (two of them occurring within 24 hours). He was treated for each overdose at three different large academic medical centers. The first three academic medical center offered him solely Buprenorphine-Naloxone, whereas the current medical center took a multimodal approach. We hypothesize that populations of color with opioid use disorder who are from a low socioeconomic class will benefit more from a multimodal approach to OUD treatment.</p> <p>Methods:<br>In this work, we conducted a literature review to construct a multitude of questions to assess Mr.G’s experience at his previous academic medical centers versus his current academic center and why his current treatment has resulted in successful opioid cessation.</p> <p>Results:<br>Thus far, we have not received a response from Mr. G. However, since a multimodal approach was taken towards his treatment, he has enrolled in college courses, has gained employment, and has maintained sobriety.</p> <p>Conclusion and Potential Impact:<br>Patients like Mr. G who come from communities of color and lower socioeconomic status may benefit from a multimodal approach when treating their OUD. This study will potentially lead to more research focusing on how to address the holistic needs for communities of color with opioid use disorder who come from a lower socioeconomic status.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Adaobi Okolocha, Jasser Khairallah, DOhttps://journals.iupui.edu/index.php/IMPRS/article/view/27755Non-Fatal Strangulation Injuries: Improving Physician Knowledge and Attitudes2023-12-07T07:27:52-05:00Sarah PankratzChristine Motzkus<p>Background and Objective:<br>In the emergency department, providers are expected to evaluate patients who have experienced strangulation resulting from sexual assault or interpersonal violence. Non-fatal strangulation can lead to significant injuries, including carotid artery dissection. Given the prevalence of strangulation injuries, providers must feel confident in their decision-making for this population. Previous educational interventions effectively improved provider knowledge of sexual assault and domestic violence patients, however, no studies have been conducted with the goal of improving provider knowledge about strangulation injuries in this population. We aimed to assess and improve emergency department provider knowledge surrounding nonfatal strangulation injuries.</p> <p>Project Methods:<br>Preintervention and postintervention surveys were administered to emergency department physicians and advanced practice providers assessing both provider comfort and knowledge regarding treatment of survivors of sexual assault, domestic violence, and strangulation. Key content areas included: physician comfort in treating sexual assault survivors, understanding of trauma-informed care, satisfaction with prior training regarding nonfatal strangulation, and physician attitudes. 6 vignette-style questions designed to evaluate knowledge in clinical scenarios were also administered. A 15-minute, interactive, educational presentation was administered during the pre-existing departmental meeting. Survey responses were collected via email and data was stored in REDCAP. Preintervention and postintervention results were compared via t-tests.</p> <p>Results:<br>There were 22 pre-intervention and 10 post-intervention responses. Median years of practice were 8. Survey participants tended to rate awareness of imaging recommendations and resources, decisionmaking, history taking, and use of trauma-informed care higher than preintervention participants. Postintervention participants tended to answer more clinical vignettes correctly than preintervention participants.</p> <p>Conclusion and Potential Impact:<br>A 15-minute educational intervention was effective in improving provider knowledge, confidence, and comfort in treating patients who have experienced non-fatal strangulation. In the future, similar interventions may be implemented in other emergency departments to increase awareness about the evaluation and treatment of nonfatal strangulation injuries.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Sarah Pankratz, Christine Motzkus, MD, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27756The Potential Tripartite Connection: Alzheimer's Disease, Fracture Healing, and the Gut Microbiome2023-12-07T07:35:49-05:00Reggie ParkerWill VarnerMurad NazzalAmy CreecySonali J. KarnikRachel J. BlosserElizabeth ScottAlexander HarrisAshlyn MorrisHannah WangTyler MargettsMarko DragisicUpasana GangulyJill C. FehrenbacherKathryn D. FischerAlexandru MovilaAdrian L. OblakJessica Hathaway-SchraderMelissa A. Kacena<p>Alzheimer's disease (AD), fracture healing, and the gut microbiome are interconnected aspects of health that have gained significant research interest. Recent studies suggest gut dysbiosis may play a role in AD pathogenesis, potentially through the gut-brain axis, a bidirectional communication system. Moreover, the gut microbiome's role in bone health could link dysbiosis and fracture risk. Furthermore, research reports have revealed that the brain communicates with bone, termed the bone-brain axis. Despite these insights, the effect of the gut microbiome on fracture healing in AD remains largely unexplored.</p> <p>To uncover these connections, our study uses the AD mouse models, 3xTg and 5xFAD. We conducted osteotomies on these mice and analyzed fecal samples that were collected at different timepoints. Fecal samples are being examined via qPCR and 16s RNA analysis to<br>identify and quantify bacterial phyla. These findings will be linked to both AD progression, gauged through behavior and histological analyses, and fracture healing, quantified using X-ray mRUST scoring, microCT, and histology.</p> <p>We hypothesize that the progression of AD could alter the gut microbiome, potentially affecting fracture healing. This might occur through inflammation pathways triggered by specific gut bacteria. We may identify specific gut bacteria that play critical roles in both fracture healing and AD. We anticipate finding a shift towards pro-inflammatory bacterial phyla in the context of AD progression and during the fracture healing process. If this hypothesis is validated, it could unlock new therapeutic strategies aimed at targeting the gut microbiome to improve bone health, fracture healing, and AD progression in patients.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Reggie Parker, Will Varner, Murad Nazzal, Amy Creecy, Sonali J. Karnik, Rachel J. Blosser, Elizabeth Scott, Alexander Harris, Ashlyn Morris, Hannah Wang, Tyler Margetts, Marko Dragisic, Upasana Ganguly, Jill C. Fehrenbacher, Kathryn D. Fischer, Alexandru Movila, Adrian L. Oblak, Jessica Hathaway-Schrader, Melissa A. Kacena, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27757Evaluation of Insertion Speed and Hand Kinematics During Cochlear Implantation in a Fixed Cadaveric Temporal Bone Model2023-12-07T08:03:26-05:00Radha PatelTroy WessonSarah Burgin<p>Background:<br>Cochlear implant is the treatment of choice for replacement of sensory deprivation from severe to profound sensorineural hearing loss. Slower insertion of the electrode into the cochlea leads to less intracochlear trauma. Accurate measures of hand motion and insertion speed during live cochlear implant electrode insertions on human subjects are limited.</p> <p>Methods:<br>Data from a single surgeon was collected during insertion of a cochlear electrode into a cadaveric temporal bone using inertial measurement units (IMUs), devices that measure linear acceleration in 3 dimensions (x,y,z). The sensors were affixed as follows: dorsal second digit, dorsal hand, and dorsal wrist with three trials at each position. The extremity inserting the electrode into the inner ear was labeled “inserting limb,” while the other extremity was labeled “non-inserting limb.” Root mean square (RMS) calculations were utilized to record the net acceleration, from which average speed per trial was calculated using the midpoint method.</p> <p>Results:<br>Mean speeds for first digit, hand, and wrist for the inserting limb were 0.23 ± 0.11, 0.15 ± 0.06, 0.16 ± 0.04 mm/s respectively. Mean speeds for first digit, hand, and wrist for the non-inserting limb were 0.26 ± 0.10, 0.13 ± 0.03, 0.16 ± 0.09 mm/s, respectively. The difference in speed between “inserting” and “non-inserting” limbs for all three IMU positions, as well as the relative speeds between all three positions, were statistically significant (p<0.001).</p> <p>Conclusion and Potential Impact:<br>Available literature suggests the mean insertion speed during live cochlear implant surgery is 96.5 mm/min (1.60 mm/s), which is significantly faster than the mean speeds collected during this fixed cadaveric temporal bone study regarding all three positions (p<0.001). Though preliminary, this data of insertions speeds highlights the need for further investigation during live cochlear implant surgery on human subjects using IMUs.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Radha Patel, Troy Wesson, Sarah Burgin, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27758Breast Cancer Disparities Among Women in Underserved Communities in Northwest Indiana2023-12-07T08:13:45-05:00Pooja PatelBasem AltarshanAmy Han<p>Background: Breast cancer is the second most common cancer found in women, after skin cancers. Research has discovered that factors such as race, socioeconomic status, and education affect both screening levels and cancer staging at diagnosis. Black women as well as lower-income individuals usually have higher grade staging as well as higher mortality. Since Lake County medical systems serve both high and low-income communities we wanted to analyze breast cancer staging in Lake County to see how it compares to national trends.</p> <p>Methods: “Hospital A” provided data from 393 positive breast cancer diagnoses along with the clinical staging at diagnosis from January 2019 to December 2022 for both high and low-income neighborhoods. Using a Mantel-Haenszel chi-square test we compared staging levels among the different income neighborhoods as well as among different races.</p> <p>Results: When looking at total staging data from 2019-2022, there was a significant difference between the race category of "Black or African American" and "White" population staging data. White patients tend to have lower stages, during initial clinical diagnosis, compared to Black patients. The "Other" category, which included all other races that did not fit into the "Black or African American" or "White Category" such as Asians, also had lower staging upon diagnosis when compared to the “Black or African American” group but no statistically significant difference with the “White” population.</p> <p>Conclusion: Our data showed that in Lake County, Indiana there are disparities in cancer staging among both income levels as well as race. The lower-income areas in our study were correlated with a greater proportion of Black residents as compared to the higher income areas. This data shows that Lake County needs to be more proactive in screening its minority communities.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Pooja Patel, Basem Altarshan, Amy Han, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27759Host-Implant Interaction Metabolite 10-HOME Mediated Dysregulation of Adiponectin Resulting in Breast Implant Associated Systemic Manifestations2023-12-07T08:22:16-05:00Ethan PulliamEthan RinneImran KhanMithun Sinha<p>Background:<br>Breast implant illness (BII) is a poorly understood systemic complication with unknown etiology. Surgical injury at the implant site initiates local inflammation, impacting adipose tissue through decreased adipose-derived adipokine expression. This acute stress responses activates lipid peroxidation pathways, generating oxylipins, causing inflammatory, nociceptive, and vascular responses to injury. One such oxylipin, (E)-10-hydroxy-8-octadecenoic acid (10-HOME), formed from oleic acid, is abundant in host-implant interaction. However, it is unclear how adipose inflammation is maintained. This study aims to elucidate how host-implant interaction<br>metabolites effect adiponectin expression, subsequently affecting T-cell differentiation eliciting an autoimmune state.</p> <p>Methods:<br>LiSa-2 (human derived adipose tissue secondary cell line) were grown in IMDM and RPMI (4:1) until confluent, then cultured in a well plate. Cultured cells were treated with 10μM 10-HOME for 48h, then were co-cultured with naïve T-cells (PBMC derived) for 48h. T-cells were harvested and flowcytometry was performed using CD4, CD184, CD194, CD196 markers and respective isotypes to verify differentiation (Th1, Th2, Th9/22). To study adiponectin gene expression, treated Lisa-2 cells were harvested for qRT-PCR. ELISA was performed using treated LiSa-2 culture media.</p> <p>Results:<br>We showed decreased expression of adiponectin, after 10-HOME treatment of LiSa-2 cells, compared to untreated cells. qRT-PCR (p=0.0022) showed downregulation of adiponectin gene transcripts in treated LiSa-2 cells, highlighting changes in modulation. Using ELISA (p=0.0006), the culture media of treated cells showed significantly less adiponectin than untreated media. Treated LiSa-2 cells led to polarization of naïve CD4+ T cells to Th1 subtype, evaluated by flowcytometry (p=0.0494). No significant difference in polarization was observed for Th2, Th9 and Th22 subtypes.</p> <p>Conclusion:<br>This study provides evidence that LiSa-2 with 10-HOME treatment caused increased Th1 polarization via modulation of adiponectin expression. Adiponectin regulates many inflammatory pathways, but its effect on Th-cell-mediated responses is poorly understood. Further studies should investigate the mechanism for adiponectin modulation causing T-cell imbalance.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Ethan Pulliam, Ethan Rinne, Imran Khan, Mithun Sinha, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27760Novel Method for Development of Nanobubbles with Consistent Size Distribution2023-12-07T08:44:18-05:00Karthik RavichandranLuis SolorioJinyang Du<p>Background/Objective:<br>Ultrasound is a versatile non-invasive clinical tool that can be used for monitoring, diagnosis, and management of disease. Contrast-Enhanced Ultrasound (CEUS) takes advantage of microbubbles which are small gas filled bubbles made of lipids to image and evaluate functioning of organs such as the heart, liver, and kidneys. CEUS is better for assessing vascularization of tissues compared to US. However, ultrasound contrast agents have been limited by their size and cannot extravasate blood vessels easily. Current methods also have high polydispersity. We hypothesize that a microfluidic device could deliver nanobubbles with improved size distribution by mixing through micro sized pores.</p> <p>Methods:<br>The microfluidic device was fabricated using 3D printing for a proof of concept and photolithography for functional use and was done in a class 1-10-100-1000 cleanroom. SU-8 photoresist was spun onto a 4” silicon wafer at 3000 rpm for 30 seconds. The silicon wafer was then baked and exposed under UV with a photomask designed on AutoCAD. The wafer was then developed, hard baked, and was cross linked with Polydimethylsiloxane (PDMS).</p> <p>Results:<br>Dynamic light scattering data of a shaken formulation shows a monodisperse distribution. Further work will have to be done to determine if this can be delivered by microfluidic device and the parameters that affect size and polydispersity.</p> <p>Conclusion and Potential Impact:<br>This study will determine the parameters needed for the microfluidic device to efficiently create microbubbles for contrast enhanced ultrasound.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Karthik Ravichandran, Luis Solorio, PhD, Jinyang Du, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27761Evaluation of a Pediatric High-Flow Nasal Cannula Training Program for Providers at Moi Teaching and Referral Hospital in Eldoret, Kenya2023-12-07T08:51:32-05:00Kaitlyn A. RobertsEmaan G. BhuttaAdnan BhuttaMegan S. McHenryPolycarp MandiEric NgetichFaith SilaHellen JemeliSarah KimettoLaura J. RuhlJoram NyandatJulika Kaplan<p>Background: High-flow nasal cannula (HFNC) is a relatively safe, effective, and well-tolerated form of non-invasive ventilation for children with respiratory distress and is regularly used in resource-rich settings. Pediatric HFNC has been successfully implemented in resource-limited settings; however, little is known about the training process required to integrate HFNC into care. The present study evaluates a pediatric HFNC training program conducted at Moi Teaching and Referral Hospital (MTRH) in Eldoret, Kenya prior to HFNC implementation at Shoe4Africa Children’s Hospital.</p> <p>Methods: This study took place within the Academic Model Providing Access to Healthcare (AMPATH) program, a partnership among MTRH, Moi University, and a consortium of North American universities led by Indiana University. The training program curriculum included information about HFNC; clinical signs of respiratory distress; a demonstration and hands-on practice with HFNC machines; a locally adapted protocol for pediatric HFNC implementation; and a sample patient case. Fifty-nine acute care providers (nurses, clinical officers, medical officers, and registrars) participated in training. Participants completed pre-tests and post-tests (immediate and 3-month follow-up) containing open-ended questions to assess HFNC knowledge and five-point Likert scale questions to assess HFNC comfort and attitudes. Data were analyzed using descriptive statistics and two-proportion Z-tests (α=0.05).</p> <p>Results: Average knowledge assessment scores significantly increased from pre-test (2.19/6) to post-test (5.59/6; p<0.001). While scores decreased slightly at the 3-month follow-up, they remained increased from pre-test levels (4.53/6; p<0.001). The percentage of respondents who answered each knowledge assessment question correctly on the post-test and 3-month followup were significantly increased from the pre-test. Participant comfort using HFNC was increased on both the post-test (p<0.001) and 3-month follow-up (p=0.038).</p> <p>Conclusions: This program successfully trained providers in pediatric HFNC use at MTRH and could inform future HFNC training in resource-limited settings. Future studies should evaluate pediatric outcomes at Shoe4Africa after HFNC implementation.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Kaitlyn A. Roberts, Emaan G. Bhutta, Adnan Bhutta, Megan S. McHenry, MD, Polycarp Mandi, Eric Ngetich, Faith Sila, Hellen Jemeli, Sarah Kimetto, Laura J. Ruhl, Joram Nyandat, Julika Kaplan, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27762Interferon Beta Modulation of Brain Endothelial Cell Activation in Ischemic Stroke2023-12-07T09:09:24-05:00August RodefeldPing-Chang KuoBarbara ScofieldJimmy Yen<p>Background and Hypothesis:<br>Every year, more than 690,000 people in the United States suffer an ischemic stroke. Many survivors are left with long-term disability. While the initial insult to the brain is caused by hypoxia resulting from cerebral artery occlusion, a secondary insult is caused by peripheral immune cell infiltration across the blood brain barrier (BBB) and subsequent cytotoxic insult. Previous studies have demonstrated that interferon beta (IFNβ) limits peripheral immune cell infiltration across the BBB and reduces brain infarction volume. We hypothesize that during ischemic stroke IFNβ suppresses brain endothelial cells (bECs) activation to reduce their expression of adhesion molecules as one of the mechanisms by which it decreases peripheral immune cell infiltration across the BBB.</p> <p>Experimental Design:<br>In this project, bEnd.3 cells, a cell line of bECs, were activated by TNF-α, a pro-inflammatory cytokine. Tissue plasminogen activator (tPA), an FDA-approved thrombolytic for ischemic stroke, was included in the study. bEnd.3 cells were treated with IFNβ at 1.5 hours prior TNF-α or TNF-α + tPA stimulation to evaluate its modulation of adhesion cell expression. The adhesion molecule expression was determined by flow cytometry. Results were further confirmed by in vivo studies in which stroke animals were subjected to tPA treatment in the presence or absence of IFNβ.</p> <p>Results:<br>Our results showed that TNF-α induced ICAM-1, VCAM-1, E-selectin, and P-selectin expression. Importantly, we found IFNβ suppressed the expression of aforementioned adhesion molecules in bEnd.3 cells treated with TNF-α or TNF-α+tPA. Our in vivo results demonstrated that IFNβ treatment reduced ICAM-1 and E-selectin, but not VCAM-1 or P-selectin expression in the ischemic brain.</p> <p>Conclusion and Potential Impact:<br>Our study demonstrates that IFNβ modulates bEC expression of adhesion molecules in vitro and in vivo of ischemic stroke, suggesting IFNβ, an FDA-approved drug for Multiple Sclerosis, shows potential to improve ischemic stroke outcomes.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 August Rodefeld, Ping-Chang Kuo, Barbara Scofield, Jimmy Yen, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27763In-Theatre Simulation as a Training Tool for Laparoscopic Salpingectomy in Eldoret, Kenya2023-12-07T09:17:28-05:00Lauren RoopSamson IliwaJenny YangWan-Ju Wu<p>Background/Objective: Minimally invasive surgery (MIS) offers many advantages over open procedures including decreased patient safety risks and reduced burden on healthcare infrastructure. As low- and middle-income countries (LMICs) are disproportionately affected by these aspects of surgery, there is motivation to increase MIS. A multimodal training program in laparoscopic salpingectomies was piloted with a small cohort of OB-GYN registrars and consultants at Moi Teaching and Referral Hospital (MTRH) in Eldoret, Kenya. This project assesses the in-theatre simulation’s (1) effectiveness in improving laparoscopic knowledge and skill confidence, and (2) feasibility for long-term implementation at MTRH and in similar settings.</p> <p>Methods: Participants completed a half-day in-theatre simulation of a laparoscopic salpingectomy. The simulation required participants to demonstrate knowledge of laparoscopic setup, proper patient positioning, procedure completion, equipment troubleshooting, and peri-and intra-operative complication management. Participants completed a multiple-choice laparoscopic knowledge quiz and Likert scale skill confidence survey immediately prior to and following the simulation. Pre- and post-simulation responses were compared to assess knowledge and confidence acquisition overall and across content topics.</p> <p>Results: There was a significant increase in the average knowledge quiz score from pre- to posttest (p=0.028). A significant difference between pre- and posttest confidence was noted in four of the six skills assessed. By topic, equipment troubleshooting (p<0.001), and complication management (p<0.01) saw the most improvement. Barriers to long-term sustainability include unpredictable theatre and laparoscopic tower access and availability of supplies for uterine modeling. A modified model using nitrile gloves as fallopian tubes will be piloted in future simulations as a more accessible alternative for long-term implementation.</p> <p>Conclusion: Despite limitations, in-theatre simulation has the potential to be an effective and sustainable teaching tool within a long-term MIS training program at Moi Teaching and Referral Hospital. The low-cost model and methods outlined may also be replicable in similar low-resource settings.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Lauren Roop, Samson Iliwa, Jenny Yang, Wan-Ju Wuhttps://journals.iupui.edu/index.php/IMPRS/article/view/27764Indiana Contraceptive Use Metrics through PATH4YOU Program: Initial Review2023-12-07T09:29:02-05:00Molly RugglesKathleen WendholtCaitlin Bernard<p>Objective—PATH4YOU is Indiana’s first state-wide contraceptive access project and provides contraceptive access via in-person and telehealth visits using a reproductive justice framework. Our objective was to evaluate outcomes of the PATH4YOU program to determine the distribution of contraceptive access among people in Indiana.</p> <p>Study Design—We analyzed programmatic data of reproductive-age people who received care in the PATH4YOU program from September 2021 to June 2023. All participants received pregnancy intention screening, comprehensive contraceptive counseling and decision support, and no-cost contraceptive method access, including long-acting reversible contraception (LARC). We evaluated age, location (county), primary method of contraception received, partner site visited, and in-person vs telehealth visit type using descriptive statistics. Geographical mapping analysis was used to determine areas of Indiana most impacted by the PATH4YOU program.</p> <p>Results—Between September 2021 and June 2023, 1,024 people received care at 1,231 visits through the PATH4YOU program. The average age of participants was 27.6 years old. A significant (49.3%) proportion of the participants live in Marion County. The most common primary methods of contraception were the implant (25.8%), contraceptive pills (20.5%), and intrauterine devices (16.0%). The most visited partner sites included People’s Health Center in Indianapolis (24.8%) and via telehealth (22.5%). Most people received contraceptive access in one in-person (66.0%) or telehealth (17.9%) visit.</p> <p>Conclusion—The PATH4YOU state-wide contraceptive access project provided a range of contraceptive methods via both in-person and telehealth visits to a wide reach of people across multiple counties in Indiana.</p> <p>Implications—The unique PATH4YOU model of care using both in-person and telehealth visits is a novel way to increase contraceptive access throughout a state with highly variable access to traditional in-person contraceptive care. Further research is necessary to evaluate direct impacts of the program on minoritized and traditionally excluded populations to evaluate long-term outcomes like maternal mortality.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Molly Ruggles, Kathleen Wendholt, Caitlin Bernard, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27765Factors Associated with Fetal Growth in Pregnancies Complicated by Type 2 Diabetes Mellitus2023-12-07T11:28:55-05:00Valeria Rutty-SerranoChristina Scifres<p>Background and Hypothesis:<br>The prevalence of type 2 diabetes (T2DM) is increasing, and it is associated with an increased risk for adverse perinatal outcomes. Fetal overgrowth is associated with an increased risk for obesity and diabetes in offspring of individuals with type 2 diabetes, and we sought to identify factors associated with excess fetal growth in pregnant individuals with T2DM.</p> <p>Experimental Design or Project Methods:<br>This was a retrospective cohort study of 350 pregnant individuals with T2DM who delivered at IU Health Hospitals or Eskenazi Hospital from January 1, 2019-December 31,2021. We excluded pregnancies complicated by twin gestation or stillbirth. Maternal demographic data and perinatal outcomes were abstracted from the electronic medical record. Birth weights were classified as small for gestational age (SGA; <10th percentile), appropriate for gestational age (AGA; 10-90th percentile), and large for gestational age (LGA; >90th percentile) using a US birth weight standard. Maternal characteristics and pregnancy outcomes were compared across the 3 categories using ANOVA and chi squared statistic. Multinomial logistic regression was used to identify factors associated with birth weight category.</p> <p>Results:<br>LGA birth weight occurred in 95 (27%) and SGA birth occurred in 32 (9%) of pregnancies. After adjusting for covariates, HbA1c after 20 weeks’ gestation was significantly associated with risk for SGA birth weight (aOR 0.4, 95% CI 0.19-0.94) and LGA birth weight (aOR 1.47, 95% CI 1.10-1.96). Individuals requiring treatment with both insulin and oral agents at the first prenatal visit were at increased risk for LGA birth weight (aOR 4.49, 95% CI 1.43-14.10).</p> <p>Conclusion and Potential Impact:<br>Our findings highlight the important relationship between glycemic control in the second half of pregnancy and fetal growth. Additional research is needed to optimize glycemic control in pregnant individuals with T2DM.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Valeria Rutty-Serrano, Christina Scifres, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27766Understanding Barriers Faced by Rural Adolescent and Young Adult Cancer Survivors2023-12-07T11:43:19-05:00Joseph SakelBrittany GassCourtney MooreBrandon CockrumBridget HawrylukLisa ParksKara GarciaTammy Sajdyk<p>Background and Hypothesis:<br>The current 5-year survival rate for adolescent and young adult (AYA) cancer diagnoses is 85.8%. However, AYA cancer survivors face many challenges including loss of insurance, infertility, sexual health concerns, physical disability, education barriers, housing instability, food insecurity, and decreased financial well-being. Survivors in rural areas may face additional challenges, such as lack of access to cancer centers, tailored resources, and networks of fellow AYA cancer survivors that may be available in large cities. The study goal was to better understand specific barriers to survivorship care for this rural population, using a comprehensive interactive workbook distributed to cancer survivors in Southwest Indiana.</p> <p>Methods:<br>A prototype workbook was distributed to 42 AYA survivors in southwest Indiana. Follow-up interviews were conducted with 11 individuals. Interviews with the first wave of eligible participants (n=7) provided perspectives on the workbook, helped identify potential improvements, and offered further insight into their survivorship experiences. These eligible participants were also invited to participate in an online forum to facilitate group discussions on potential improvements to the workbook. Responses were evaluated through affinity mapping to identify common themes.</p> <p>Results:<br>AYA cancer was found to have a lasting impact on physical health, mental health, and relationships for many of the AYA survivors. Importantly, only 27% of participants who completed the workbook responded “yes” to having received a survivorship care plan, suggesting barriers in communication between survivors and healthcare providers. Regarding overall health, the three largest barriers identified by cancer survivors in rural southwest Indiana were insurance coverage, mental health services, and the availability of services needed.</p> <p>Conclusion:<br>To strengthen survivorship care to rural survivors, our study suggests a need for better distribution and explanation of survivorship care plans, as well as increased access to stable insurance, medical services, and mental health services.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Joseph Sakel, Brittany Gass, Courtney Moore, Brandon Cockrum, Bridget Hawryluk, Lisa Parks, Kara Garcia, PhD, Tammy Sajdyk, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27767Development of a Novel Atherosclerotic Heart Disease Biomarker Program2023-12-07T11:54:02-05:00John P. SalvasCynthia JohnsonSubha V. Raman<p>Background: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of heart attack, stroke, and sudden death worldwide. Clinical risk scores help estimate the likelihood of adverse cardiac events to guide preventative strategies. Current risk scores for atherosclerotic events like heart attack and stroke use known cardiovascular risk factors including smoking, diabetes, lipid levels, and blood pressure. However, these scores underestimate risk in certain patient populations and do not predict the atherosclerotic disease in individual patients that leads to subsequent events. Our aim is to design a novel biomarker-enabled model to predict the presence and burden of coronary artery atherosclerosis in patients with diabetes, to ultimately help personalize preventive therapies that target disease burden, not just risk factors, for more effective prevention of ASCVD events.</p> <p>Methods: Patients with diabetes have been prospectively enrolled in a health plans-based screening program with co-enrollment in the Indiana Biobank, which includes coronary CT angiography, an AI-based quantitation of atherosclerosis, and biobanking of DNA, plasma, and serum. We identified candidate biomarkers based on current literature and determined which could be impactful based on cost, efficacy, and feasibility of implementation guided by interviews with potential collaborating entities.</p> <p>Results: We have identified polygenic risk scores, non-coding RNAs and candidate blood biomarkers with predictive potential for atherosclerotic heart disease. Subsequent work will entail i) direct assays of banked biospecimens for the selected minimally invasive biomarkers and ii) computational analysis to assess incremental predictive value for disease burden over clinically available risk scores.</p> <p>Conclusions and Potential Impact: We are progressing towards the development of a novel mode to predict patient-specific burden of coronary atherosclerotic disease burden in patients with diabetes. We expect that a multidimensional approach including contemporary biomarkers will improve predictive value of atherosclerotic heart disease burden, affording more tailored treatment to prevent ASCVD events.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 John P. Salvas, Cynthia Johnson, Subha V. Raman, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27768Retrospective Analysis of COVID-19 Impact on Social + Emotional Development in Children of Low-Income Communities from Head Start2023-12-07T12:06:23-05:00Gabrielle S. LiSatya P. SanapatiAmy Han<p>Background:<br>Geminus Head Start is a federal program that works with children under five years old from low-income communities to promote school readiness. The organization in Northwest Indiana provided anecdotal data on delayed social and emotional development of children during the pandemic. Studies have shown that adverse childhood development can have a severe psychological and physiological impact on health outcomes into adulthood. However, there has been a lack of research on quantifying the extent of damage from the pandemic on our Head Start children, who mainly identify as Black/African American.</p> <p>Methods:<br>Geminus Head Start provided demographic data including race, postal codes and DECA for over 4650 students from 2019-2023. DECA, Devereux Early Childhood Assessment, is used by educators to evaluate children’s social emotional competence for early intervention. In this study, we are investigating the DECA categories, including initiative, self control, and attachment/relationships. We analyzed DECA scores via ANOVA along with listening into the teacher focus groups.</p> <p>Results:<br>Students had increased attachment/relationship scores from the 2019-2020 school year to the 2020-2021 school year (36.69 to 44.59). However, following COVID-19 to the 2021-2022 and 2022-2023 school years, these scores dropped to 23.51. When looking at the second protective factor, self regulation, the opposite trend was found. The scores went from 18.79 in 2019-2020 down to 14.68 in 2020-2021 and eventually up to 23.51 in 2021-2022.</p> <p>Conclusion:<br>Like most institutions, the pandemic has created a time of isolation and instability for our children and their families. In particular, these children have not been able to access adequate conditions to develop emotional and social maturity. Lacking this development can lead to several negative health outcomes as it may impact mental health and the ability to create healthy supportive networks.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Gabrielle S. Li, Satya P. Sanapati, Amy Han, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27769Immune Infiltrate Profiling of Cutaneous Melanoma with Spatial Transcriptomics2023-12-07T12:12:41-05:00Meghana SankarHong-Ming ZhouQun WangYunglong LiuXiaoling XueiHongyu GaoAhmed AlomariSimon WarrenMatthew Turner<p>Background and Objective:<br>In 2023, an estimated 97,610 melanomas will be diagnosed in the U.S. Immunotherapy has revolutionized care for melanoma patients and highlighted the prognostic value of characterizing immune infiltrates in melanoma tissue. This project used spatial transcriptomics (ST) to analyze immune infiltrates in cutaneous melanoma specimens.</p> <p>Methods:<br>Visium Spatial Gene Expression platform generated datasets from formalin fixed paraffin embedded cutaneous melanoma specimens were analyzed using Loupe Browser software v6.5.0 (10x Genomics Inc.). Unsupervised clustering and manual region selection identified areas enriched in immune cell specific differentially expressed genes (DEGs). The transcript for Collagen alpha-1(XIX) chain (COL19A1) was identified as a DEG co-expressed with B cell marker DEGs. Fluorescence activated cell sorting was used to isolate primary B and T cells from mouse secondary lymphoid organs and human peripheral blood mononuclear cells to measure COL19A1 with quantitative PCR (qPCR).</p> <p>Results:<br>Transcripts for CD19 (B cell marker) were concentrated in an immune DEG- rich region adjacent to a melanoma micrometastasis in one specimen. There was overlap between the tertiary lymphoid structure [TLS] markers SELL, CXCR5, CCR7, and CXCL13 with CD19 and/or COL19A1. Though qPCR revealed minimal Col19a1 in mouse B and T cells, COL19A1 was abundant and specific for human B cells.</p> <p>Conclusions & Potential Impact:<br>This study demonstrates the feasibility and potential of using ST to characterize immune cell infiltrates in melanoma. Though COL19A1 expression is typically understood to be enriched in muscle and neuronal cells, the studies presented here suggest this transcript could be a novel human (but not mouse) B cell marker. Future studies are needed to determine if collagen XIX (protein) is expressed in B cells and if it is, what the biological functions of this protein are in B cells under physiologic and pathologic (e.g. melanoma) conditions.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Meghana Sankar, Hong-Ming Zhou, Qun Wang, Yunglong Liu, Xiaoling Xuei, Hongyu Gao, Ahmed Alomari, Simon Warren, Matthew Turner, PhD, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27771Trends in Melanoma Patient Survival Based on Tumor Depth and Anatomic Location2023-12-07T12:31:33-05:00Bhavi SardaJustin CouetilKun HuangJie ZhangAhmed K. Alomari<p>Skin cancer is the most common cancer. Melanoma composes less than 4% of total cases but is the cause of most skin cancer deaths. However, in the United States, melanoma has the fifth highest rate of incidence of all cancers with an average 93.5% 5-year survival rate. However, when melanoma spreads either to regional lymph nodes or to distant organs, the prognosis drops significantly, so there is a critical need to identify patients at risk for tumor spread. The objective of this research project is to determine the correlation between tumor depth and anatomic location with metastasis outcomes. We identified a cohort of 923 Stage 1 & 2 patients (those without lymph node metastases) from the Indiana University Simon Cancer Center Registry with an average follow up of 4 years (Std. dev = 3.2). We retrieved the clinicopathologic descriptions of their melanomas using a database from the IU Pathology department. Patients were stratified by tumor stage, location, and depth of invasion, and survival rates were analyzed Cox proportional hazard models and log-rank tests. Kaplan-Meier plots were generated with the survminer package. The results of the study indicate that there is no difference in metastasis for patients with similar levels of tumor invasion but different anatomic locations. Unexpectedly, multivariate cox regression showed that mitotic count was a stronger predictor of metastasis than tumor invasion. These results indicate that there is a need for bioinformatic tools to more accurately quantify semi-quantitative measures of tumor morphology. This would allow for rigorous research and higher precisions prognostic tools.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Bhavi Sarda, Justin Couetil, Kun Huang, PhD, Jie Zhang, Ahmed K. Alomarihttps://journals.iupui.edu/index.php/IMPRS/article/view/27772Sex differences in region-specific hippocampal areas in Alzheimer’s Disease: an animal-based approach2023-12-07T12:47:36-05:00Jackson SawyerSyed Salman ShahidYu-Chien Wu<p>Background: Atrophy in the hippocampus is responsible for memory and cognitive decline in Alzheimer’s Disease (AD). Progression and presentation of AD in men and women are different, and the hippocampus and its subregions could be affected differently. By identifying what areas of the hippocampus are affected by sex, diagnostic tools can be better used to clinically identify and treat AD.</p> <p>Aims: The goals of the proposed research are: (1) use in vivo MRI techniques to isolate the hippocampus in a mouse model, (2) use data analysis to compare the volume of the hippocampus and its subregions in 5xFAD mice, and (3) see if sex plays a role in differing hippocampal volume, and (4) assess the translational utility of using structural MRI to measure hippocampal integrity for future in vivo human brain studies/clinical practice.</p> <p>Methods: We used the imaging software FSLeyes to examine MRI images and isolate hippocampal subregion masks. MRI images were taken at the 2-month age period when amyloid-B deposition begins in the forebrain. Upon isolation of the hippocampal mask of each MRI, group classification was identified, and quantitative analysis was performed to compare groups.</p> <p>Results: We found significant lower spatial volume in Stratum Granulosum (SG) of the hippocampus in female mice compared to male mice. The SG contains dentate granule cells, responsible for spatial memory. Apart from this, the data that we obtained was nonsignificant but did show that female mice contained mainly smaller hippocampus subregions and total volumes despite TICV being larger in females.</p> <p>Conclusion and Impact: More data is needed to observe the degeneration of SG over a lifetime and assess if it is the reason why males retain spatial memory in AD as opposed to females. Otherwise, analyzing hippocampal volume in the early stages of AD doesn’t appear to be sufficient in explaining outstanding sex differences in AD presentation and progression.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Jackson Sawyer, Syed Salman Shahid, Yu-Chien Wu, MD, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27773Association of Case Duration with Late vs. Early Physical Therapy Initiation in Treatment of Work-Related Musculoskeletal Injuries: A Retrospective Analysis2023-12-07T12:58:32-05:00Grant SawyersAmelia RoebuckAmanda CoupeMichael KnippTungyun Wu<p>Background:<br>Occupational medicine providers treat patients who are injured while working. Conservative management with over-the-counter anti-inflammatory medicines, physical modalities (ice/heat), and activity restrictions are first-line treatment strategies. Physical therapy (PT) is often added to assist with patients’ return to baseline through symptom reduction and restoration of function. PT efficacy on outcomes and healthcare costs has been described in other patient populations but less described in injured worker populations. This study focused on associations between PT timing and case duration for treating musculoskeletal injuries in a regional injured worker<br>population.</p> <p>Methods:<br>A retrospective chart review of 795 patients receiving care at Parkview Occupational Health (POH) for musculoskeletal injuries from 2017-2023 was conducted to determine if early PT was associated with case duration. Patients employed in Indiana and referred to PT within Parkview were included in the study. Age, BMI, and case duration were compared between early vs. late PT groups using two-sampled t-test. Race, sex, smoking status, and injury type were compared using chi-squared tests.</p> <p>Results:<br>The mean case duration (73.41 days) when PT was initiated early (≤ 30 days after date of injury, DOI) was significantly shorter compared to the mean case duration (104.21 days) when PT was initiated late (p<0.0001). Case duration was even shorter (67.61 days) when early PT was defined as ≤14 days after injury (p=0.001). There was no significant difference in case duration (mean difference=9.5 days) between patients initiating PT within 14 days and within 15-30 days (p=0.15). Injury type (back vs. other musculoskeletal injuries) was significantly associated with PT timing (p=0.002).</p> <p>Conclusion/Implications:<br>Future analysis should compare case duration, days of restricted work, advanced imaging utilization, and specialist referral rate between patients with early and late PT initiation. This comparison will aid in development of best practice guidance for treatment of work-related musculoskeletal injuries at POH.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Grant Sawyers, Amelia Roebuck, MD, Amanda Coupe, Michael Knipp, Tungyun Wu, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27774Energizing the Lung Vasculature in the Premature Infant to Promote Alveolar Formation2023-12-07T14:32:51-05:00Mackenzie SchaffAndrew KimEvan ArsenaultMary MusselmanDushani RanasingheMargaret Schwarz<p>Background/Objective: Chronic lung disease of prematurity, bronchopulmonary dysplasia (BPD) occurs when infants born with underdeveloped immature lungs are forced to navigate the expansion of future air spaces, with irregular vascular formation proceeding development of BPD. Lung development has distinct and dynamic metabolic requirements. We recently identified by mass spectrometry that nicotinamide adenine dinucleotide (NAD+), generated from vitamin B3 ‘Nicotinamide’ (NAM), was significantly reduced in a hyperoxia murine model of BPD. As NAM/NAD+ are dynamic regulators of tissue regenerating neovascularization in other<br>disease processes, we hypothesized that NAM/NAD+ metabolic deficiencies contribute to compromised angiogenesis formation and alveolar formation.</p> <p>Methods: Impact of NAM supplementation on circulating human neonatal endothelial colonyforming cells (ECFCs) were assessed for differential capillary formation properties of angiogenesis (Matrigel), migration (wound healing), proliferation (WST1 and crystal violet<br>staining), and mitochondrial function in normoxia and hyperoxia (85% oxygen) conditions.</p> <p>Results: Hyperoxia suppresses ECFC angiogenesis, while NAM supplementation in hyperoxia significantly rescued vascular networks, branched nodes, and branch points (p<0.001). Wound healing assays suggest that NAM promotes cell migration in normoxia and hyperoxia (p<0.0001). Although NAM increased WST1 activity in hyperoxia, crystal violet analysis determined that NAM had no impact on ECFC proliferation. Lastly, NAM significantly reduced hyperoxia induced mitochondrial oxidative stress in a dose dependent manner (p<0.05).</p> <p>Conclusion and Clinical Implications: Lung development has specific metabolic needs during different stages of development that are disrupted by premature birth. Replenishment of NAM promotes angiogenesis and migration in hyperoxia while reducing mitochondrial activity. Future studies are necessary to explore the role of NAM/NAD+ axis in the developing lung.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Mackenzie Schaff, Andrew Kim, Evan Arsenault, Mary Musselman, Dushani Ranasinghe, Margaret Schwarz, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27776Elevated Psychiatric Comorbidities in Patients with Low-risk Chest Pain Presenting in The Emergency Department2023-12-07T15:31:44-05:00Linh DangKurt KroenkeTimothy StumpPatrick MonahanJill ConnorsYelena CherynakPaul Musey<p><strong>Background/Objective:</strong> Low-risk chest pain (LRCP), i.e. chest pain that does not pose an imminent risk or have a cardiovascular cause, constitutes the majority (80%) of cases of chest pain presenting to the emergency department (ED). Past research shows that in patients with<br>LRCP without a history of cardiovascular disease, many will meet criteria for panic or generalized anxiety disorder. The purpose of this project is to examine the psychiatric comorbidities of patients with LRCP including differences by severity of anxiety.</p> <p><strong>Methods:</strong> Baseline data collected in the Patient-Centered Treatment of Anxiety after Low-Risk Chest Pain in the Emergency Room (PACER) study were analyzed to determine: the rates of depression, somatization, posttraumatic stress disorder (PTSD), disability, and low self-efficacy<br>in relation to increasing levels of anxiety (low anxiety but positive for panic disorder vs moderate vs severe anxiety). Also, anxiety severity groups are compared for demographic and other patient characteristics to identify potential predictors of anxiety severity.</p> <p><strong>Results:</strong> In 265 patients with LRCP who screened positive for panic disorder and/or generalized anxiety disorder, the proportion with low, moderate and severe anxiety symptoms was 9%, 44% and 47%, respectively. Overall, 57% (n=150) also screened positive for depression, 54%<br>(n=144) for somatization syndrome, and 56% (n=149) for PTSD. Rates of depression, somatization, PTSD, and disability increased as the level of anxiety increased. Compared to patients with low to moderate anxiety, patients with severe anxiety were more likely to have depression (odds ratio = 3.0), somatization (OR = 2.7), PTSD (OR = 2.6), disability (OR = 2.4), and low self-efficacy (OR = 3.5).</p> <p><strong>Conclusion and Potential Implications:</strong> Patients with LRCP and anxiety are likely to have other psychiatric comorbidities. Additionally, as rates of comorbidities increase with the anxiety severity, detection and management of anxiety is essential to provide optimal care for low-risk<br>chest pain.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Linh Dang, Kurt Kroenke, MD, Timothy Stump, Patrick Monahan, Jill Nault Conners, Yelena Cherynak, Paul Musey, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27777Exploring Relationships Between Fear of Cancer Recurrence, Psychological Distress, and Mental Health Service Use in Breast Cancer Survivors2023-12-07T15:47:46-05:00Ana DannerMatthew HaysYang LiShelly Johns<p><strong>Background:</strong> Breast cancer survivors (BCS) have an increased risk of psychological distress compared with healthy controls. Fear of cancer recurrence (FCR) is one of the most reported forms of distress, with approximately 50% of BCS reporting clinically significant FCR. Designed to give alternatives to avoidant coping, acceptance and commitment therapy (ACT) has shown promise in reducing distress and FCR in BCS. The primary objective of this study was to explore relationships between psychological distress and mental health service use in BCS with FCR.</p> <p><strong>Methods:</strong> Baseline data from 384 early-stage, post-treatment BCS with clinically significant FCR at screening enrolled in an RCT comparing 3 FCR interventions were analyzed. Prevalence of clinically significant FCR and symptoms of anxiety, depression, and posttraumatic stress was measured. Associations between each distress measure and mental health service use were assessed, in addition to the association between FCR and avoidant coping.</p> <p><strong>Results:</strong> Clinically significant levels of at least one form of psychological distress besides FCR were reported in 226 (58.85%) BCS. Of 298 (77.60%) BCS with at least one significant distress score including FCR at baseline, only 61 (20.47%) reported using any mental health service within the 3 months before baseline. Clinically significant anxiety (p = 0.0027), depression (p = 0.0015), and post-traumatic stress symptoms (p = 0.0227) were significantly associated with mental health service use. FCR was significantly associated with fewer visits to certain mental health services. FCR was strongly correlated with increased avoidant coping (ρ = .6313, p < .0001).</p> <p><strong>Conclusion:</strong> Anxiety, depression, and post-traumatic stress symptoms may be better predictors of mental health service use than FCR given the tendency for patients with fear to cope with avoidance. ACT interventions emphasizing alternatives to avoidant coping may benefit BCS with FCR. Further research is needed to identify barriers to mental health service use in BCS.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Ana Danner, Matthew Hays, Yang Li, Shelly Johns, PsyD, MS, HSPP, ABPPhttps://journals.iupui.edu/index.php/IMPRS/article/view/27778Amyloidosis in the Head and Neck: A Case Presentation and Literature Review2023-12-07T15:58:47-05:00Neeti DaveBenjamin Anthony<p><strong>Background:</strong> As reported by the Cleveland Clinic, amyloidosis is a rare disease that affects 5 to 12 out of every 1 million people worldwide. Of those affected, 19% present with amyloidosis of the head and neck. Amyloidosis results from the accumulation of insoluble amyloid protein in<br>tissue due to improper synthesis and processing of proteins. Amyloidosis of the head and neck region is rare and can be localized or systemic. Surgical intervention is often necessary to remove the amyloid tissue. Dr. Benjamin Anthony and Dr. Hector Mesa encountered a case of head and neck amyloidosis at an Indiana University hospital. An investigation of this case reveals the disease’s presentation, diagnosis, and treatment.</p> <p><strong>Project Methods:</strong> The patient’s data and surgical pathology reports were collected and formatted for analysis. Histological images of the pathology slides and laryngoscopy footage were obtained for examination. The case data was then compared to a literature review of other similar cases. After the comparison, the effectiveness of surgical treatments was analyzed and areas for future research were identified.</p> <p><strong>Results:</strong> After review of the literature and case, tissue biopsy followed by mass spectrometry was determined to be an effective diagnostic method. The literature and case differed in the clinical presentations they reported and the surgical intervention they concluded was most effective. Most literature reported the CO2 laser to be the most effective at resecting the disease, while the case review indicated the laryngeal coblator.</p> <p><strong>Conclusion and Potential Impact:</strong> Despite the need for further research in diagnosing and treating amyloidosis, the literature and the case demonstrate effective methods exist. Research into treatment poses a greater need due to surgical limitations and potential morbidity. Ongoing research will analyze data from past Indiana University Health cases to evaluate diagnostic methods and treatment approaches. Thus, providing valuable insights for improving patient care.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Neeti Dave, Benjamin Anthony, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27779Silencing COQ8B in Aortic Smooth Muscle Cells Reveals Cellular Dysfunction Related to Changes in Cell Proliferation2023-12-07T16:23:18-05:00Joshua DavisBenjamin Landis<p><strong>Background/Objective: </strong>Thoracic aortic aneurysm (TAA) is a prevalent disorder that predisposes to aortic dissection. Prior work identified the ubiquinone biosynthesis gene COQ8B as a genetic modifier of TAA progression. We sought to determine the impact of decreased COQ8B on global transcription in aortic smooth muscle cells (SMCs).</p> <p><strong>Methods: </strong>Primary human aortic SMCs from a healthy donor were seeded in 12-well plates. Six experimental conditions were created, each with 3 replicates: 1) siRNA targeting COQ8B (siCOQ8B); 2) siRNA targeting the dominant TAA gene SMAD3 (siSMAD3); 3) negative control<br>siRNA (siNeg); 4) siCOQ8B and siSMAD3; 5) siCOQ8B with Angiotensin II (AngII) stimulation (siCOQ8B+AngII); 6) siNeg+AngII. RNA was extracted approximately 48 hours post-siRNA transfection and, for AngII conditions, after 1 hour of incubation with AngII (100 nM). mRNAsequencing was performed and downstream analysis utilized R packages EdgeR and topGO.</p> <p><strong>Results:</strong> Multidimensional scaling identified distinct clustering of samples by experimental condition. Downregulated genes in siCOQ8B were enriched for Gene Ontology pathways related to cell proliferation including cell cycle regulators, DNA replication, and mitosis. MYOCD, a master regulator of SMC homeostasis, was downregulated. Similar proliferation-related pathways were enriched in siCOQ8B+siSMAD3 and siCOQ8B+AngII compared to siNeg. Pathways related to cell proliferation in siCOQ8B+AngII cells were downregulated when compared to siCOQ8B which indicates that AngII infusion in the context of COQ8B silencing may further dysregulate cell proliferation pathways.</p> <p><strong>Conclusion: </strong>The results indicate that COQ8B has an important role in cell cycle processes in aortic SMCs, including when SMCs are exposed to stressors associated with TAA development. Stimulation of angiotensin receptors may exacerbate the effects of decreased COQ8B in these processes. To investigate these experimental results in human pathology, bulk RNA samples and intact nuclei have been isolated from frozen human aortic specimens and prepared for transcriptomic analysis.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Joshua Davis, Benjamin Landis, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27781Blood Culture Contamination Rates in Bloomington, Association with Patient History2023-12-08T03:58:30-05:00Vanessa SchwietermanAimee LeeChristine Motzkus<p>Background/Objective: Blood cultures are vital for diagnosing infections and directing antibiotic therapy to causative organisms in systemically ill patients. Blood culture contamination contributes to increased costs, longer lengths of stay, and unnecessary antibiotic use. Certain patient histories and demographics have been associated with higher contamination rates. Identifying contamination risk factors within the hospital may allow for improvements in patient care.</p> <p>Methods: Patient demographics, history, and blood culture information were identified through a chart review for all adult blood cultures collected in January 2023 at the IU Health Bloomington Hospital. Patient characteristics collected included age, race, ethnicity, BMI, and a number of comorbidities (COPD, diabetes, etc.). Blood culture characteristics, including the number of cultures drawn, hospital setting, etc., were also collected. A comparative analysis was performed between positive, negative, and contaminated cultures.</p> <p>Results: In January, 443 adult patients had blood cultures collected at IUH Bloomington hospital, with contamination in 33 cases (7.4%). Patients with contaminated cultures had a higher prevalence of hypertension (75.8%) compared to those with negative cultures (61.9%). Type II diabetes was more prominent in the contaminated culture group (36.4%) than the negative culture group (31.3%). 15.2% of patients with contaminated cultures resided in extended care facilities, while only 12.3% of patients with negative cultures did so. Most contaminated cultures (97%) were drawn in the emergency department, with 3% collected in medical-surgical units/floor level of care.</p> <p>Conclusion: Features of patient history, demographics, and culture collection may be associated with higher blood culture contamination rates.</p> <p>Scientific/Clinical/Policy Impact and Implications: This data will be expanded into the entire 1st quarter of 2023 to further identify trends in culture contamination. Findings may present opportunities for quality improvement in patient care as IUH Bloomington looks to further reduce their rates of contaminated cultures.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Vanessa Schwieterman, Aimee Lee, Christine Motzkus, MD, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27782Biopsy or no biopsy? Risk of Malignancy in Thyroid Nodules Based on TI-RADS Criteria2023-12-08T04:07:06-05:00Faadil ShariffVivek Halappa<p>Purpose: To assess the risk of malignancy in thyroid nodules recommended for biopsy using the American College of Radiology (ACR) Thyroid Imaging Reporting & Data System (TIRADS).</p> <p>Methods: We conducted a retrospective review of ultrasound (US) guided thyroid biopsies performed from 2018- 2023 at IU Health hospitals for nodules which were recommended for biopsy based on ACR TI-RADS criteria and compared with histopathology results. The research was conducted at University and Methodist Hospital radiology reading rooms.</p> <p>Results: Of the total 210 thyroid nodules recommended for biopsy, only 8.57% of nodules biopsied were malignant. Positive malignancy rate for TR-3 was 10.2%, TR-4 was 7.1%, and TR-5 was 12.5%. TR-3 nodules less than 2.9 cm were all benign on histopathology. TR-4 nodules less than 1.5 cm were all benign on histopathology. TR-5 nodules were all benign on histopathology. The most common malignancy was papillary thyroid carcinoma.</p> <p>Conclusion: ACR TI-RADS is currently the standard of care for guidelines and lexicon for radiologists for characterizing thyroid nodules. Our results demonstrate that all TR-3 nodules less than 2.9 cm were all benign and most of the TR-4 and TR-5 nodules biopsied were benign on histopathology. The lower biopsy rate for positive malignancy even for TR-4 and TR-5 nodules respectively raises the need for revision for existing TI-RADS criteria, as more nodules could be followed up with ultrasound rather than percutaneous biopsy, which will alleviate patient anxiety as well as decrease overall healthcare costs.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Faadil Shariff, Vivek Halappa, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27783Retrospective Analysis of Suicide Deaths in Allen County Indiana, 2013 – 20222023-12-08T04:15:24-05:00Kathleen ShermanAaron WilliamsJana SandersThomas Gutwein<p>Suicide rates at a national and state level have been on the rise over the past two decades. Patterns observed at the local level is less understood and underrepresented in research. Since local government can have a large impact on resource allocation in a community, revealing local suicide patterns could help facilitate targeted preventative efforts for at-risk populations. This study aims to analyze demographic patterns observed in Allen County suicides from 2013 –2022, focusing on age groups and education attainment. Data collection was completed on the 604 individuals who died by suicide in Allen County over the past decade. The collection process included documenting various demographics accessed through death certificates and coroner’s files. Within the county, suicide numbers increased over the decade. Results showed that males represented more than a 3:1 ratio of total suicides, a gunshot wound was the method of injury for 53% of all suicides, and decedents with a high school degree or less represented 62% of suicides within the population. These results echo what research has shown at the national level. Additionally, the 20-34 and the 35-54 age groups produced the greatest number of suicides consistently over the 10 years, and these suicides occurred most often in late spring and early summer. Within the 20-34 age group, individuals were more likely to commit suicide by gunshot wound (p = 0.000133). Decedents of minority ethnic and racial groups had lower education attainment compared to non-Hispanic (p = 0.000027) or white (p = 0.003314) individuals. This information could be provided to local schools with the hopes of implementing more targeted preventative measures for at-risk groups. Knowledge of suicide patterns in healthcare could lead to improved care for patients. Finally, public health entities can use these findings to adapt current health initiates to fit the needs of Allen County.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Kathleen Sherman, Aaron Williams, Jana Sanders, Thomas Gutwein, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27784Evaluating the Utility of Procalcitonin and C-Reactive Protein to Predict Bacteremia in Children with Musculoskeletal Infections2023-12-08T04:35:04-05:00Alex SmithJames Wood<p>Background:<br>Musculoskeletal infections (MSKI; osteomyelitis, septic arthritis) are among the most common invasive bacterial infections in children, often associated with complications. Bacteremia precedes these complications; thus, early identification may prevent them. Acute inflammatory markers, C-reactive protein (CRP) and Procalcitonin (PCT) are often elevated in children with acute MSKI. PCT is understudied in children with MSKI. The primary goal of this study was to evaluate the utility of PCT and CRP in distinguishing children with MSKI with bacteremia vs. those without.</p> <p>Methods:<br>Patients 6 months to 18 years with strong clinical suspicion of MSKI were prospectively enrolled at Riley Hospital for Children from July 2019 to May 2022 unless clinical evidence suggested an alternative diagnosis or if informed consent was not obtained. CRP was obtained at admission and PCT was collected within 96 hours of presentation to the hospital. Demographic data was recorded from electronic medical records. Two-sided P values of <0.05 were considered statistically significant for univariate analysis and logistic regression.</p> <p>Results:<br>Thirty-seven patients were enrolled, the majority being non-Hispanic white males (40.5%), median age of 8 years (IQR, 4-12). Median PCT in children with bacteremia was higher (0.41 ng/mL [IQR 0.14-0.8 ng/mL]) compared to those without (0.10 ng/mL [IQR 0.05-0.31 ng/mL]) (p=0.03). Median CRP in children with bacteremia was higher (13.7 mg/dL [IQR, 9.15-19.9]) compared to those without (4.1 mg/dL, [IQR 0.65-5.8]) (p<0.01). Both PCT and CRP showed good ability to discriminate those with bacteremia from those without, with an area under the ROC of 0.75 (95% CI 0.56, 0.94) and 0.80 (95% CI 0.64, 0.95), respectively.</p> <p>Conclusions:<br>Initial PCT and CRP demonstrated utility in detecting bacteremia in patients presenting with MSKIs. This study warrants further exploration into the usage of PCT and CRP as early predictors of bacteremia for more appropriate treatment and potentially fewer complications of these infections in pediatric patients.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Alex Smith, James Wood, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27785MicroRNA-150 (miR-150) as a Potential Biomarker for Diabetic Retinopathy2023-12-08T05:02:54-05:00Conner SmithQianyi LuoNeha MahajanAshay Bhtwadekar<p>Diabetic retinopathy (DR) is a known chronic complication of diabetes mellitus and is one of the leading causes of visual impairment. The chronic inflammation associated with DR poses large risks not only for the vasculature but also for the surrounding neuronal tissue. Potential biomarkers, especially those surrounding microRNAs (miRNAs), have been proposed to indicate the progression of DR. Levels of certain miRNAs have been shown to be either down or upregulated in type 1 diabetes patients and have shown correlations with specific types of DR. MicroRNA-150 (miR-150) has also been shown to have protective effects on cells in hypoxic environments, but when downregulated, miR-150 actually induces apoptosis. And, it has been shown to be downregulated in patients with type 1 and type 2 diabetes as well as patients with obesity. We hypothesize then that the levels of miR-150 from a peripheral blood sample should be indicative of the progression of DR and may be used for potential early intervention. In this project, we assessed miR-150 levels in the peripheral blood mononuclear cells (MNCs) of individuals with different severities of DR by isolating mononuclear cells and extracting RNA. We then reverse-transcribed the RNA into cDNA and used RT-qPCR to measure the levels of miR-150 in individuals with varying DR severity. MiR-150 levels in the MNCS were decreased in individuals with diabetes with no retinopathy, moderate NPDR and severe NPDR groups when compared to control individuals; however, there was a marginal increase in the miR-150 mild NPDR group. The data could show evidence that a peripheral blood draw could be used as a less invasive approach to assessing the severity of diabetic retinopathy in patients. This would change the disease management and future treatments individually.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Conner Smith, Qianyi Luo, Neha Mahajan, Ashay Bhtwadekar, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27786A Review of SNAP Nutritional Incentive Programs2023-12-08T05:08:32-05:00Dylan SogocioAntonia SawyerDennis Savaiano<p>There are over 40 million Americans in the Supplemental Nutrition Assistance Program (SNAP), formerly known as the Food Stamps Program. Despite this program attempting to eliminate food insecurity for people 130% below the poverty line, it does little to prevent nutrition related health disparities between SNAP participants and people who are more financially stable. Nearly every state has nutrition incentive programs attempting to address these nutritional health disparities that SNAP does not address. To synthesize a literature review of several of these programs, a search was conducted in PubMed, PubAg, and Google Scholar databases using terms such as “SNAP” and “nutritional incentive program,” along with date restrictions for 2013 or later. This search resulted in a total of 54 articles, however only 35 were used following screening. Included articles were screened first by abstract and then article content to determine relevancy. The literature suggests that programs address nutritional health disparities by providing financial interventions for SNAP participants to make nutritionally conscious decisions about the food they purchase and consume. There were three categories of interventions that were suggested by the literature: incentives, discounts, and restrictions. Regardless of the intervention, each of these categories of intervention were praised by SNAP participants. Participants were able to purchase and consume more fruits and vegetables, focus on nutrition, and financially support local farmers markets and supermarkets. This review discusses these different interventions to allow for new or existing programs to be developed to best address nutritional health disparities using scholarly evidence.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Dylan Sogocio, Antonia Sawyer, Dennis Savaiano, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27787Perioperative Risk Factors Predicting Hardware Exposure after Mandibulectomy and Reconstruction2023-12-08T05:19:19-05:00Mychael T. SpencerAlexander J. JonesAvinash V. Mantravadi<p>Background and Hypothesis:<br>Mandibulectomy is often required in the management of tumors, infection, or trauma of the head and neck. Reconstruction of the defect is accomplished via osteocutaneous free flaps and the use of titanium plates for fixation of the bone segments. Postoperative exposure of the mandibular hardware is an unfortunate outcome which results in significant quality of life detriment and often requires substantial revision surgery and reconstruction. We hypothesize that individuals with vasculopathic conditions and other circumstances that contribute to poor wound healing are more likely to experience hardware plate exposure following mandibular reconstruction.</p> <p>Methods:<br>A single-institution, retrospective cohort study was performed on all adults undergoing mandibulectomy and osteocutaneous free flap reconstruction from 2010-2020. Demographics, patient history, surgical parameters, and follow-up data were collected. Comparisons and logistic regression were used to determine factors associated with postoperative hardware exposure.</p> <p>Results:<br>The cohort consisted of 134 predominantly white (92.5%) male (65.7%) patients with mean age 58.4±13.0 years, 32 (23.9%) of whom had postoperative plate exposure. Between patients with and without exposure, there were no differences observed in demographics, substance use, surgical indications, or reconstructive techniques, neoadjuvant or adjuvant chemoradiation, nor 30-day major surgical site infection. The comorbidities of peripheral vascular disease, hypothyroidism, and immunosuppression were significantly more common in the plate exposure group. In multivariate logistic regression, peripheral vascular disease (OR [95%CI] = 18.8 [1.8-196.3]), hypothyroidism (OR [95%CI] – 3.5 [1.1-10.6]), and immunosuppression (OR [95%CI] =11.3 [2.4-54.1]) remained significant predictors of post-mandibulectomy hardware exposure.</p> <p>Conclusion and Potential Impact:<br>Patients with pre-existing peripheral vascular disease, hypothyroidism, and/or immunosuppression have an increased risk of post-mandibulectomy hardware exposure. Understanding these risk factors can improve shared patient-surgeon decision making and counseling, as well as guide practitioners to focus on mitigating these comorbidities prior to surgery.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Mychael T. Spencer, Alexander J. Jones, Avinash V. Mantravadi, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27788Exploring a Transcriptome-forward Approach for Genetic Evaluation in Thoracic Aortopathy2023-12-08T05:29:05-05:00Katherine StanleyBenjamin Landis<p>Background/Objective: Thoracic aortic aneurysm (TAA) is an aortopathy that predisposes to aortic dissection and rupture. Transcriptomic analysis has diagnostic utility in other diseases, but this has not been developed for TAA. We therefore sought to implement the Genome Analysis Toolkit (GATK) as a tool for high-throughput detection of novel variants in RNA sequencing (RNA-seq) data from patients with TAA.</p> <p>Methods: Human proximal aortic tissue samples from 63 TAA patients and 15 controls were used to establish primary smooth muscle cell (SMC) lines in culture. Total RNA was extracted at early passage; RNA-seq was performed using 150 base pair paired-end reads. Variants were called from RNA-seq reads using the GATK’s HaplotypeCaller tool. The MarkDuplicates tool tagged duplicate reads, but these were retained for variant analysis. Singletons were defined as heterozygous variants unique to one sample in the overall group.</p> <p>Results: The RNA-seq pipeline was validated by confirming known mutations in 2 patients, inspecting reads directly in the Integrative Genomics Viewer (IGV), and genotyping for a common single nucleotide polymorphism. Across all 78 samples, the GATK pipeline identified 4,823,462 variant sites, 236,495 of which were in coding regions. Variant sites were filtered for those located within the coding regions of 31 genes curated for known evidence of aortic disease causality. Among the 511 coding variant sites in these genes, 330 single nucleotide variants and 33 insertions/deletions were identified as singletons. Singleton variant calls were evaluated for quality and annotated in order to predict their likelihood of pathogenicity, thus far identifying strong candidate causal variants in FBN1, TGFBR1, TGFB3, GATA4, and HEY2.</p> <p>Conclusion: Application of the GATK RNA-seq pipeline expands our prior IGV analysis, further demonstrating the potential diagnostic utility of transcriptomic analysis of aortic SMCs in TAA.</p> <p>Scientific Impact: Identifying novel aortopathy-associated variants could improve future disease detection and prediction of severity.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Katherine Stanley, Benjamin Landis, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27789Electronic Health Record-based Surveillance of Hypertension Prevalence2023-12-08T05:33:34-05:00Justin StilesBrian E. Dixon<p>Background:<br>Public health officials require timely, accurate data to guide decision-making. The Behavioral Risk Factor Surveillance System (BRFSS), a nationwide telephone survey of U.S. adults conducted by the CDC, serves as a primary source for chronic disease prevalence data. However, limitations like small sample sizes and publication delays exist. A promising alternative is Electronic Health Record-based (EHR) surveillance. Under the CDC-funded Multi-state Electronic Health Record-based Network for Disease Surveillance (MENDS) project, the Regenstrief Institute utilizes EHR data from the Indiana Network for Patient Care database to detect hypertension using algorithms based on a combination of blood pressure measurements, diagnostic codes, and antihypertensive prescriptions.</p> <p>Methods:<br>We compared hypertension prevalence estimates between BRFSS and MENDS using 2015 data from Indiana residents. BRFSS included individuals who positively reported a diagnosis of hypertension or antihypertensive medication use. MENDS included individuals based on clinical diagnosis, abnormal blood pressure readings, and medication history. Gestational hypertension and end-stage renal disease cases were excluded. Equivalence was empirically tested using the two one-sided t-tests (TOST) statistical method.</p> <p>Results:<br>TOST analysis revealed the two methods were not equivalent overall (p < 0.0001) or in any strata measured. The EHR-based model produced a lower estimate of 18.7% (95% CI ± 7.1 x 10-6, n=10,800,076), while BRFSS produced a higher estimate of 28.4% (95% CI ± 3.8, n=934).</p> <p>Conclusion:<br>BRFSS might overestimate (i.e., too sensitive) hypertension prevalence due to survey methodology, while the EHR-based model might underestimate (i.e., too specific) due to its more complex hypertension-detection algorithm. Nevertheless, the EHR-based model provides a reliable and more timely method for estimating hypertension prevalence.</p> <p>Implications:<br>MENDS provides estimates for other chronic disease risk measures such as diabetes, smoking, and obesity. Participating health departments receive updated data each month and can monitor trends. By providing reliable and timely data, public health officials can make well-informed decisions to serve their communities.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Justin Stiles, Brian E. Dixon, PhD, MPAhttps://journals.iupui.edu/index.php/IMPRS/article/view/27790Induced Pluripotent Stem Cell-Derived Mesenchymal Stromal Cells Promote Muscle Regeneration in a Diabetic Mouse Model of Critical Limb Threatening Ischemia2023-12-08T05:42:42-05:00Ali SualehTheresa DoironChang-Hyun GilJennifer StashevskyOlivia JimezStone ChenNancy ZhangHumraaz SamraSteven J. MillerMichael P. Murphy<p>Critical limb threatening ischemia (CLTI), the end stage of peripheral arterial disease (PAD), is diagnosed in 500,000 patients each year, often results in amputation, and has a ~50% 5-year mortality rate. Diabetic CLTI patients experience especially high morbidity and mortality, and no effective non-surgical therapy exists for this population. Our Phase II MOBILE trial demonstrated that autologous bone marrow nucleated cells were unable to prevent amputations in diabetic patients; however, data from a Phase I trial shows that allogeneic bone marrow-derived mesenchymal stromal cells (BMD-MSC) stimulated angiogenesis in ischemic muscle, including diabetics. While allogeneic MSC may be an effective cell preparation to treat diabetic CLTI, passaging-related cell senescence prevents generation of sufficient cell numbers for therapeutic use. The development of induced pluripotent stem cell (iPSC)-derived MSC overcomes cell senescence issues and offers the possibility of genetic modifications to enhance cell function. The current study was designed to determine potential mechanisms by which iPSC-MSC stimulate muscle regeneration in a rodent CLTI model.</p> <p>The CLTI mouse model was created by ligation/excision of the femoral artery in male polygenic diabetic TallyHo mice. Mice with intramuscular administration of iPSC-MSC displayed positive indicators of muscle regeneration compared to vehicle control mice. Real-time PCR performed with gastrocnemius muscle obtained 7- or 30-days post iPSC-MSC injection showed an increase in mRNA expression for MyH3, MyoD1, Mrc1, FoxP3, and VEGF-A vs. vehicle treated muscle, indicating promotion of muscle regeneration, M2-biased macrophage expression, T regulatory cell (Treg) expansion, and vascular proliferation. Downregulation of the NADPH<br>oxidase subunit p47phox indicated a decrease in oxidative stress in the treated mice. The results are consistent with iPSC-MSC promotion of muscle regeneration via a Treg mediated stimulation of the M1-M2 macrophage phenotypic shift. Thus, human iPSC-MSC could be an effective treatment to stimulate muscle regeneration and ameliorate CLTI in diabetic patients.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Ali Sualeh, Theresa Doiron, Chang-Hyun Gil, Jennifer Stashevsky, Olivia Jimez, Stone Chen, Nancy Zhang, Humraaz Samra, Steven J. Miller, Michael P. Murphy, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27791Parkinson’s Disease Progression: Exploring the Relationship between Motor Performance and Cognitive Function2023-12-08T05:52:10-05:00Megan E. SullivanAditya A. ShanghaviSarah Elizabeth ZauberAnne B. Sereno<p>Background/Objective: Numerous studies have examined motor and cognitive decline in neurodegenerative diseases such as Parkinson’s Disease (PD) and results vary considerably. Studies also show that decline does not occur synchronously across all aspects of cognition or motor functions in PD. The goal was to examine if correlations exist between decline in specific motor and cognitive functions.</p> <p>Experimental Design: A cohort of 15 PD patients (age 49-81;6 female) and 9 healthy controls (age 53-75;4 female) were enrolled and their motor and cognitive functions were assessed. Decline in motor function, covering tremor, rigidity and bradykinesia was evaluated using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MS-UPDRS) scores. Cognition, covering attention, memory, language, and visuospatial functions, was assessed using the Montreal Cognitive Assessment (MoCA) test. Inertial measurement units (recording at 100 Hz), placed on both wrists, recorded linear acceleration and angular velocity while subjects performed the pronation/supination and kinetic tremor tasks of the MS-UPDRS. Using angular velocity, response time (RT) to initiate movement in each task was computed. Data analysis correlated MS-UPDRS scores with MoCA scores, and RTs.</p> <p>Results: There were no significant correlations between MS-UPDRS and cognitive MoCA scores. There was a significant relationship between deficits in visuospatial function (MoCA) and increased RT in the pronation/supination task.</p> <p>Conclusion/Potential Impact: Using correlation analyses, no correlation was found between MS-UPDRS and MoCA scores. However, RT on the pronation/supination task correlated positively with visuospatial deficits, suggesting a common voluntary attentional deficit. Although no relationship was found between a clinical score of bradykinesia and RT, measures of movement velocities (measured but not analyzed) may correlate better. Identification of interrelating factors between hard-to-measure cognitive and easy-to-measure motor changes in PD patients may aid clinicians in implementing simple and timely interventions to more easily track and ameliorate cognitive deficits and improve patients' overall functional status.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Megan E. Sullivan, Aditya A. Shanghavi, Sarah Elizabeth Zauber, Anne B. Sereno, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27792Geographic location as a variable to Home Gardening Interventions in Rural Indiana2023-12-08T06:00:12-05:00Maggie SuttonLynn WittyCatherine MeadorW. Holmes Finch<p>Background/Objective: The purpose of this study was to evaluate attitudes of a wide variety of persons towards barriers to home gardening and desired interventions for home gardening in multiple locations in the Muncie, Indiana area. The health benefits of gardening are well known, but little research has been done evaluating the ability or interest in home gardening in areas with significant populations of minorities or those with low socioeconomic status. Taste enhancing herbs or fresh and nutritious vegetables in food insecure areas could be invaluable. This study evaluates which interventions were preferred and needed based on geographic location in Muncie. Our hypothesis was that respondents from a garden fair in Muncie would be more likely to want more information than respondents from other locations.</p> <p>Methods: A survey designed for a research study focusing on barriers to home gardening was deemed to be appropriate to use for analysis for this study, because it included several questions about desired and needed interventions. The survey asked respondents to write contact information if follow-up interventions or classes were desired. Cross tabulation was used to analyze the relationship between multiple variables in the survey.</p> <p>Results: There is a statistically significant relationship between where the person was surveyed and whether they wanted to sign up for more information. 68.8% of respondents at the Minnetrista Garden Fair desired more information, compared to 0% of respondents at the Yorktown Farmer’s Market.</p> <p>Conclusion: There was in fact a relationship between location surveyed and desire for more information, but this relationship isn’t as simple as location. The type of event and number of people attending the event also likely impacted results. Scientific/Clinical/Policy Impact and Implications: Results from this study will be used in further work to develop gardening related information and programs for those surveyed who wish to participate.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Maggie Sutton, Lynn Witty, MD, Catherine Meador, W. Holmes Finchhttps://journals.iupui.edu/index.php/IMPRS/article/view/27793A Comparison of the Effectiveness Between Trabeculectomy and Minimally Invasive Glaucoma Surgeries2023-12-08T06:07:13-05:00Esa SyedLouis Cantor<p>Background and Hypothesis: Glaucoma affects 3 million Americans and is the second most common cause of blindness globally, after cataracts. It involves the degeneration of the optic nerve, often associated with increased eye pressure, leading to vision loss. Trabeculectomy was traditionally the standard surgical approach for managing glaucoma progression once medication and laser had failed. Recently, minimally invasive glaucoma surgeries (MIGS) have gained FDA approval for mild and moderate cases and are being implemented in practice. We hypothesize that MIGS procedures are just as effective as trabeculectomy in mild, moderate, and severe cases of glaucoma.</p> <p>Experimental Design or Project Methods: Using data from IU Health, patients that underwent either a MIGS procedure or a trabeculectomy for open-angle glaucoma at least a year ago were identified. Visual field data was used to stage their glaucoma. Any future glaucoma surgery was noted. Using this information, three separate Kaplan-Meier curves at 95% confidence intervals were created corresponding to each stage of glaucoma with a second surgery defined as a failure and a survival analysis was done to visualize the difference between these surgical approaches.</p> <p>Results: The sample included 119 patients and 179 eyes with a mean age of 80 and 57% females. The study had 80% power at a two-sided 5% significance level. Based on the survival analysis, there were no significant differences between trabeculectomy and MIGS in mild and moderate glaucoma (p=0.69 and 0.97 respectively). In severe glaucoma, MIGS had a lower failure rate compared to trabeculectomy (p=0.026).</p> <p>Conclusion and Potential Impact: The research comparing trabeculectomy to MIGS is still relatively new and this study shows the safety and efficacy of MIGS procedures. If confirmed, this study could potentially change the standard of care to MIGS for all stages of open-angle glaucoma.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Esa Syed, Louis Cantor, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27794Assessing the Self-Rating Scale Item as a Measure for Lactulose Adherence2023-12-08T06:13:10-05:00Stacey TamNicole GarciaEric Orman<p>Background/Objective:<br>Hepatic encephalopathy (HE) is a defining complication of end-stage liver disease. The standard treatment is lactulose, but adherence is difficult due to complex dosing regimens and side effects. We adapted a single item self-reported adherence measure - the Self Rating Scale Item (SRSI) - for lactulose use and examined its relationship with clinical events, cognition, and quality of life.</p> <p>Methods:<br>We performed a cross-sectional study of patients with cirrhosis and HE seen at Indiana University Hospital 5/31/2023-7/14/2023. Clinical history and demographic information were collected through electronic health records and patient interviews. Patients provided the SRSI, which reflects their self-perceived ability to take lactulose, bowel movement frequency, perception of missing doses, and quality of life (PROMIS-29+2). Cognition was measured using the Animal Naming Test (ANT). The relationship between the SRSI and other measures was assessed.</p> <p>Results:<br>42 patients met eligibility criteria and enrolled. The median age was 59, and 55% were female. Patients were divided across SRSI categories: ≤good, very good, and excellent. Patients with better adherence were more likely to have ascites, but other demographics were similar between groups. Ascites was present in 43%, 64%, and 93% of ≤good, very good, and excellent categories, respectively. A higher SRSI score was associated with fewer missed doses and more days achieving bowel movement targets. 79% in the ≤good category skipped lactulose doses compared to 29% and 21% in very good and excellent groups. SRSI was not associated with HE-related hospitalizations or ANT. Higher SRSI was associated with improved sleep and cognitive function, with a trend towards decreased fatigue and pain.</p> <p>Conclusion/Potential Impact:<br>The SRSI is associated with other measures of lactulose adherence and quality of life and may be a promising tool to measure lactulose adherence. Adopting the SRSI may be a useful way to improve lactulose dosing, adherence, and health outcomes.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Stacey Tam, Nicole Garcia, Eric Orman, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27795Prenatal Predictors of Survival, Pulmonary Hypertension, and ECMO in Isolated CDH Undergoing Expectant Management, A Systematic Review and Meta-analysis2023-12-08T06:21:50-05:00Meera A. ThielAlena N. TofteAsma KhalilHiba J. Mustafa<p>Background and Hypothesis: Congenital diaphragmatic hernia (CDH) is a severe developmental defect affecting 1-4 per 10,000 births, characterized by left/right-sided defect, or mixed with herniation of abdominal contents into thorax, with resultant lung hypoplasia and persistent pulmonary hypertension (PHTN). The study investigates prenatal predictors of survival to hospital discharge, PHTN and the need for ECMO in fetuses with isolated CDH undergoing prenatal expectant management.</p> <p>Project Methods: We performed a systematic literature review on prenatal diagnostic tests in fetuses with isolated CDH undergoing expectant management. Primary outcomes included survival-to-hospital discharge, persistent PHTN within 28 days, and ECMO need. Newcastle Ottawa Scale assessed quality of studies. Meta-analysis performed when two or more studies reported on the same test. Subgroup analysis performed according to CDH side.</p> <p>Results: 161 full-text articles between 2000-2022 were assed for eligibility; 48 met inclusion criteria. 45 reported on survival, 12 on ECMO need, 8 on PHTN; quality of studies was moderate. Studies included were retrospective (81%) or prospective (19%) regarding fetuses undergoing expectant management (77%), or mixed tracheal occlusion and expectant management (20%). Most studies included mixed (41%) or left-sided (47%) CDH. Survival predicted by TFLV, o/e-TFLV, o/e-TFLV <30%, LiTR, o/e-LHR, o/e-LHR <25%, percentage herniated liver, MSA, stomach position in mid-chest, and liver up. ECMO need predicted by o/e-TFLV, o/e-LHR, and PPLV. These results were confirmed through subgroup analysis of only left-sided lesions. PHTN was predicted by presence of intrathoracic liver (OR-1.96, 95%CI 1.14,3.37, I2-0%); this was not significant after left-sided subgroup analysis.</p> <p>Conclusion and Potential Impact: In fetuses with CDH, FLV and presence/percentage of intrathoracic liver predict survival. FLV measurements predict ECMO need. Presence of intrathoracic liver may predict persistent PHTN; further studies are needed. Accurate prognostication of CDH severity would aid patient triage, resource mobilization, and identification of high-risk CDH infants in need of advanced treatment including ECMO or identification of candidates for fetal intervention procedures.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Meera A. Thiel, Alena N. Tofte, Asma Khalil, Hiba J. Mustafa, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27798Social Determinants of Health Associated with Inpatient Admissions for Congestive Heart Failure, Diabetes, Chronic Obstructive Pulmonary Disease, and Asthma2023-12-08T12:34:57-05:00John DeckbarKelly DeMichaelWael GadBaraka MuvukaJonathan Guerrero<p><strong>Introduction:</strong> The CDC and American Lung Association estimate that congestive heart failure (CHF), diabetes, chronic obstructive pulmonary disorder (COPD), and asthma (COPD/asthma) cost Americans $30.7 billion, $327 billion, and $50 billion respectively each year. They account for most inpatient readmissions at St. Mary Medical Center (SMMC), an urban hospital in Northwest Indiana. There is need for further research on the social, behavioral, and demographic determinants associated with these conditions. This study examined the social, behavioral, and demographic determinants associated with inpatient admission for CHF, diabetes, COPD/asthma in SMMC’s service area.</p> <p><strong>Methods:</strong> This retrospective study was part of a multi-phased Community-Based Participatory Research partnership between SMMC and Indiana University School of Medicine Northwest. SMMC implemented a pilot screening and referral program to assess social determinants of health in their service area as part of their Hospital Readmission Reduction Program. This study included data from 10,953 inpatient admissions between January 2021 to March 2023, majority of whom were transferred from the emergency department. Data analysis consisted of<br>univariate, bivariate (Chi-square), and multivariate (binary logistic regression) analysis in SPSS 29.0.</p> <p><strong>Results:</strong> Bivariate analysis revealed a statistically significant association between CHF and smoking, age, insurance type, and income. Diabetes was significantly associated with smoking, smokeless tobacco use, age group, race, income, and sex. COPD/asthma was significantly associated with smoking, age group, transportation needs, stress, insurance, ethnicity, and sex. Multivariate analysis found the following significant associations: age group with both CHF (p<0.001) and diabetes (p<0.001), former smoking with both CHF (p = 0.007) and COPD/asthma (p = 0.049), current smoking with COPD/asthma (p = 0.016), and sex with diabetes (p <0.001).</p> <p><strong>Conclusions:</strong> These findings indicate significant associations between multiple sociobehavioral factors and admission for CHF, diabetes, COPD/asthma. Multi-risk-factor interventions may address these interactions and contribute to reducing readmission.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 John Quentin Deckbar, Kelly DeMichael, Wael Gad, Baraka Muvuka, Jonathan Guerrero, PharmDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27799Validation of Blunting of Inflammatory Markers in LPS Induced Tissue with SPM Treatment2023-12-08T13:00:58-05:00Cristina DelgadoPeyton RobinsonKhalid KhanVijay Ramakrishnan<p><strong>Background and Hypothesis:</strong> Chronic rhinosinusitis (CRS) is defined as persistent inflammation of the mucosa of the nose and paranasal sinuses, either with or without nasal polyps. The pathophysiology of CRS is thought to occur due to a dysfunction of the immune response leading to prolonged NF-kB signaling. Many chronic diseases like CRS have been shown to have chronic NF-kB dysregulation. One hypothesis for the persistent inflammation seen in CRS patients is that they have a less robust pro-resolution response that aids in termination of the NF-kB pathway. In this study, we sought to validate our previous results from nasal polyp tissue using qPCR for key inflammatory mediators, CXCL1, CSF3, and myd88.</p> <p><strong>Methods:</strong> Human CRS nasal polyp tissue was collected during functional endoscopic sinus surgery to be grown in cell culture. The nasal polyp tissue was grown in 10 ug/ml of LPS to mimic gram-negative conditions commonly seen in CRS. Tissue cDNA was extracted and frozen at – 80° C. Tissue cDNA for control, RvD2, LPS, and LPS+RvD2 was thawed and used to run qPCR for myd88, CXCL1, and CSF3.</p> <p><strong>Results:</strong> qPCR data was normalized using GAPDH and B-actin. When normalized with GAPDH and B-actin, CSF3 was found to be downregulated with RvD2 exposure, while both myd88 and CXCL1 showed inconsistent results. Downregulation of CSF3 with RvD2 exposure, is consistent<br>with our hypothesis that RvD2 plays a role in NF-kB resolution.</p> <p><strong>Conclusion:</strong> Downregulation of the NF-kB pathway can play an important role in reducing the chronic inflammation seen in CRS. CSF3 was one gene target of the NF-kB pathway that was continuously found to be downregulated when nasal polyp tissue was treated with RvD2. Our<br>findings demonstrate that when nasal polyp tissue is treated with pro-resolving mediators such as RvD2, at least one or more of the NF-kB-associated genes are downregulated.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Cristina D. Delgado, Peyton Robinson, Khalid Khan, Vijay R. Ramakrishnan, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27800Socio-Demographic and Behavioral Predictors of Admission for Kidney Disease in an Urban Hospital in Northwest Indiana2023-12-08T13:30:27-05:00Kelly DeMichaelBaraka MuvukaJonathan GuerreroKyle Gosporadek<p><strong>Background:</strong> The CDC estimates more than 1 in 7 American adults have Chronic Kidney Disease (CKD) and nearly 800,000 live with End-Stage Renal Disease (ESRD); the majority of whom require dialysis. Current literature demands further exploration on how social determinants of health (SDOH) influence inpatient and emergency services utilization for CKD/ESRD-related exacerbations. This study examined socio-demographic and behavioral factors associated with hospital admission for CKD/ESRD. It is part of a three-phased Community-Based Participatory Research (CBPR) partnership between IUSM-NW and St. Mary Medical Center (SMMC) to examine and address relationships between SDOH, patient demographics, health behaviors, and health outcomes from January 2022-January 2025.</p> <p><strong>Methods:</strong> This retrospective study analyzed a limited dataset generated by SMMC from EPIC™ with SDOH, demographic, health behavior, and health outcomes data obtained from adult inpatients between January 2021 and March 2023. CKD/ESRD was determined by admission diagnosis ICD-10 Code N18. Data analysis utilized SPSS 29.0 to produce frequencies, Chi-Square tests (p<0.05), and a binary logistic regression (p<0.05). This study was exempted by Indiana University Human Research Protection Program (IRB # 14040).</p> <p><strong>Results:</strong> This study included 10,953 inpatient admissions involving predominantly white (78.4%) and older adult (68 ± 21) patients. CKD/ESRD represented 96 admissions. The bivariate analysis found a significant association between CKD/ESRD admissions and age (p<0.001), race (p<0.001), sex (p=0.008), insurance type (p=0.030), and smoking tobacco use (p=0.004). After adjusting for all factors, being Asian (OR=12.172, p<0.001), Black (OR=3.702; p<0.001), female (OR=0.518; p=0.003), publicly insured (OR=2.76; p=0.014), and former smoking (OR=1.606; p=0.045) were significantly associated with CKD/ESRD admission.</p> <p><strong>Conclusions:</strong> This study revealed several demographics, SDOH, and health behaviors associated with CKD/ESRD admission in an urban hospital. Uncovering predictors of CKD/ESRD admission enables focused interventions to decrease admissions. The next CBPR phases will apply advanced statistical analyses to further explore these relationships and codevelop interventions.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Kelly DeMichael, Baraka Muvuka, Jonathan Guerrero, Kyle Gosporadek, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27801SSRI Efficacy in Treating Major Depressive Disorder: Preliminary Findings2023-12-08T15:04:23-05:00Samantha DesironBrian York<p><strong>Background:</strong> Conflicting evidence on the relative effectiveness of second-generation antidepressants has made initial management of major depressive disorder (MDD) complex and frequently results in a trial-and-error-based approach to treatment. With recent literature suggesting serotonin plays no significant role in the etiology of depression, further investigation of selective serotonin reuptake inhibitors (SSRIs) as a firstline treatment of MDD is warranted.</p> <p><strong>Methods:</strong> A retrospective chart review of patients 18 years or older visiting the Fort Wayne Family Medicine Center and completing a Patient Health Questionnaire (PHQ) or Generalized Anxiety Disorder scale (GAD) from January 2020 through May 2023 was performed. Comparative analysis of PHQ and GAD scores was performed to determine if any differences in treatment management outcomes were present between SSRI therapy and other treatment approaches.</p> <p><strong>Results:</strong> 1,502 patients met the inclusion criteria. Due to time constraints, a sample of 45 patients (10 males, 35 females) was selected and preliminary results are as follows: After initiating treatment with an SSRI, 14 (42.4%) PHQ scores and 7 (24.1%) GAD scores demonstrated improved disease severity. After initiating treatment with another antidepressant class, 10 (31.3%) PHQ scores and 17 (48.6%) GAD scores demonstrated improved disease severity. There was no significant difference (p=0.351) in treatment outcomes between antidepressant class in terms of PHQ results, but a significant difference (p=0.044) was found between groups with regards to GAD results.</p> <p><strong>Conclusions:</strong> This study describes preliminary findings on the current patterns of care for mental health within a primary care setting and demonstrates antidepressant classes appear equally efficacious in treating depression. However, anxiety management outcomes appear to be influenced by antidepressant class administered. Future analysis will include the entire available dataset and produce more robust results from which to improve patient-specific and community health outcomes.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Samantha Desiron, Brian York, DOhttps://journals.iupui.edu/index.php/IMPRS/article/view/27802Health-Related Quality of Life Correlates with Bladder and Bowel Dysfunction: the Need for a New Patient-Centered Questionnaire2023-12-08T15:10:22-05:00Hannah DillonBenjamin WhittamRichard RinkMartin KaeferKirstan MeldrumJoshua RothPankaj DangleYifan MengJeremy KoehlingerRosalia MisseriKonrad Szymanski<p><strong>Background and Hypothesis:</strong> Children with voiding dysfunction (VD), such as incontinence or urinary frequency, may report lower quality of life (QOL) compared to their peers. QOL questionnaires which could be used in this population have several limitations. PinQ is a bladder-specific, health-related QOL questionnaire, but it was developed without stakeholder input and fails to separate symptoms from QOL. Kidscreen-10 is a generic QOL questionnaire. We aimed to understand how QOL captured using existing instruments correlates with VD severity in a cross-sectional study. We hypothesized that large differences in symptoms would correspond with large differences in bladder-specific QOL but small differences in generic QOL.</p> <p><strong>Methods:</strong> We recruited children 8-18 years old with VD at a pediatric urology clinic (June-July 2023). VD included daytime incontinence, enuresis, frequency, urgency, and dysuria. We excluded children with severe developmental delay, anatomical urological abnormalities, or history of<br>urologic surgery. We captured demographics, symptoms (Vancouver Dysfunction Voiding Symptom Score, DVSS), and QOL (PinQ and Kidscreen-10). Questionnaire scores were compared to weighted means from previous studies. We calculated Spearman correlations and QOL differences corresponding with the reported 20-point range of DVSS scores.</p> <p><strong>Results: </strong>Twenty children (11 girls) at a median age of 10 years old participated (Table 1). Mean DVSS score was 14, similar to previous studies (weighted mean: 15). PinQ scores had a moderate positive correlation with DVSS scores (r = 0.37) with a 20-point DVSS difference corresponding to a 24% difference in PinQ scores (Figure 1). Kidscreen-10 scores had a moderate negative correlation with DVSS scores (r = -0.33) with a 20-point DVSS difference corresponding to a 12% difference in Kidscreen-10 scores (Figure 2).</p> <p><strong>Conclusions: </strong>Previously published QOL questionnaires have significant limitations, limiting their clinical use in the care of patients with VD. A new, patient-centered, highly specific, and sensitive healthrelated QOL questionnaire is needed.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Hannah Dillon, Benjamin Whittam, Richard C. Rink, Martin Kaefer, Kirstan Meldrum, Joshua D. Roth, Pankaj Dangle, Yifan Meng, Jeremy Koehlinger, Rosalia Misseri, Konrad M. Szymanski, MPH, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27803HB007 Administration Inhibits LN-229 and Patient-Derived Neurospheroid Glioblastoma Cell Growth With the Degradation of SUMO1 and Cell Cycle Regulator CDK42023-12-08T15:21:12-05:00Carson DoughertyReagan WohlfordSunghan JungChunhai Hao<p><strong>Background and Hypothesis:</strong> Glioblastoma is the most common and malignant brain cancer and there is no effective therapy currently available to patients with this malignancy. Small ubiquitin-related modifier 1 (SUMO1) is a key regulator of cancer cell proliferation through its role in its modification of cellular proteins in various human cancers, especially glioblastoma. Degradation of SUMO1 through small molecule degrader, HB007, has been shown to inhibit growth in cancer cell lines and xenografts. Here, we hypothesize that HB007 can inhibit the glioblastoma cell growth through degradation of SUMO1 protein in glioblastoma cells and the cancer stem cell enriched neurospheres.</p> <p><strong>Experimental Design: </strong>LN-229 glioblastoma cell viability was measured in response to increasing concentrations of HB007. LN-229 and patient-derived neurospheroid glioblastoma cells were cultured and seeded in 4 different plates at 1000 cells/ml concentrations before being treated with HB007 at increasing concentrations encircling the previously described IC50. Cells were then subjected to a SUMO lysis buffer and analyzed via western blot with antibodies specific to SUMO1, CDK4, and actin.</p> <p><strong>Results: </strong>HB007 treated LN-229 cells exhibited an IC50 of 1.470μM. Western blot analysis confirmed the dose dependent reduction in SUMO-1-ylated proteins in HB007 treated cells. A reduction in CDK4 confirmed that cell progression is halted in a dose dependent manner in LN-229 and patient-derived neurospheroid glioblastoma cells when treated with HB007. Specificity of HB007 is towards SUMO1 with no nonspecific degradation of SUMO2/3.</p> <p><strong>Conclusion: </strong>The cell growth of LN-229 and patient-derived neurospheroid glioblastoma cells was confirmed, through western blot, to be inhibited in a dose dependent manner by HB007. These results further establish the therapeutic potential of SUMO1 degraders as a novel anticancer drug for glioblastoma therapy. In the future, it is hoped that the bioavailability, potency, and blood brain barrier permeability can be improved to make this drug a potential treatment for patients.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Carson Dougherty, Reagan Wohlford, Sunghan Jung, PhD, Chunhai Hao, MD, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27805Clinician Perspectives on Risks and Benefits of Sharing Cardiovascular Implanted Electronic Device (CIED) Data with Patients2023-12-09T03:27:46-05:00Brandon TranCarly DaleyStephanie PruittJonathan ShiraziTina AllmandingerTammy ToscosMichael Mirro<p>Background and Objective: Cardiovascular implantable electronic devices (CIEDs) are critical, life-saving devices that are essential for the clinical decision-making process due to the data they collect. Because not all patients have ready access to their device data, there may be a clinical care gap where the CIED data are not being used most effectively in the care of patients with CIEDs. However, sharing CIED data may risk harming clinician-patient relationships and necessitates further study into clinician’s perspectives on CIED data sharing. The objective of this study was to explore clinicians’ perspectives on sharing CIED data with their patients and explore the perceived benefits and concerns.</p> <p>Methods: Clinicians involved in CIED care in the United States were recruited for semi-structured phone interviews. Participants were asked questions regarding their experiences and perspectives in sharing CIED data, and were presented scenarios to assess how they would leverage the CIED data in particular situations. Responses from the participants were analyzed by one researcher using thematic analysis.</p> <p>Results: Of the 28 clinicians interviewed in this study, the majority were white (85.7%) and located in the midwestern United States (67.9%). Participants included cardiac device clinic nurses and electrophysiology nurses (28.6%), electrophysiologists (25%), electrophysiology advanced practice providers (APPs) (17.9%), cardiologists (14.3%), and cardiology APPs (14.3%). The following themes were identified: (1) Patient engagement with healthcare, (2) Patient selfadvocacy, (3) Patients cannot interpret CIED data, (4) One size does not fit all.</p> <p>Conclusion and Potential Impact: Clinicians perceived both potential benefits and harms from CIED data sharing. Clinicians noted that CIED data sharing has the potential to increase patient participation in their healthcare, but it also can cause increased patient anxiety due to insufficient patient education. This study demonstrated some of the ways CIED data sharing may affect clinical practice involving CIEDs and the challenge of sharing complex data elements with patients.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Brandon Tran, Carly Daley, PhD, MS, Stephanie Pruitt, Jonathan Shirazi, Tina Allmandinger, Tammy Toscos, Michael Mirro, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27806Brain activation during scene encoding fMRI in the Alzheimer’s disease continuum: Association with amyloid and tau burden in PE2023-12-09T03:50:04-05:00Mia S. TruebloodAndrew J. SaykinShannon L. Risacher<p>Background and Hypothesis:<br>This project assessed brain activation during a scene encoding task in 4 groups: older adults who were cognitively normal (CN), subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia due to Alzheimer’s disease (AD). Associations between scene encoding related brain activation and tau, amyloid, and other biomarkers were analyzed. Our hypothesis was that higher levels of cerebral tau and amyloid would be associated with reduced scene encoding activation. In addition, we hypothesized that scene encoding activation would be significantly different between cognitively normal and cognitively impaired groups.</p> <p>Methods:<br>234 individuals from the Indiana Memory and Aging Study (79 CN, 67 SCD, 70 MCI, and 18 AD) completed structural and functional MRI, clinical/cognitive assessment and biomarkers; 155 underwent amyloid ([18F]florbetapir/[18F]florbetaben) PET, while 111 also underwent [18F]flortaucipir PET. For the fMRI scene encoding task, participants were asked to view and remember a set of images. A one-way ANOVA test was used to analyze scene encoding related activation differences among the 4 groups. Regression was used to identify associations between scene encoding activation and tau and amyloid deposition.</p> <p>Results:<br>Significant differences in activation were observed between the MCI and CN groups, including less activation in widespread regions during the task and reduced deactivation in the default mode network (DMN) in MCI participants relative to CN. Significant associations between higher amyloid and tau deposition and altered scene encoding activation were also observed.</p> <p>Conclusion and Potential Impact:<br>Cognitive decline is associated with activation changes during scene encoding, as well as reduced deactivation in the DMN, especially in the posterior cingulate region. Higher cerebral amyloid and tau deposition predicted decreased scene encoding related activation. These findings are consistent with models linking cognitive status, functional brain activation during episodic encoding, and pathophysiological processes in the AD continuum.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Mia S. Trueblood, Andrew J. Saykin, Shannon L. Risacher, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27807Osteoblast Transcriptome Changes During Iron Deficiency2023-12-09T04:18:08-05:00Shyam PolacondaGang PengErica Clinkenbeard<p>Introduction:<br>Chronic kidney disease (CKD) often results in iron deficiency anemia and bone loss. Previously, iron deficiency was found to impede normal osteoblast differentiation. To investigate regulatory mechanisms elicited by iron deficiency we utilized unbiased RNA-sequencing to evaluate transcriptome-level changes over the course of differentiation.</p> <p>Methods:<br>Mouse progenitor clone 2 (MPC-2) cells were differentiated in osteogenic media with or without an iron chelator, deferoxamine (DFO; 5 μM). RNA was extracted at 3, 7, and 14 days after initiating differentiation. Library generation and sequence alignment was performed by the Center for Medical Genomics (CMG). Count-based algorithms implemented in R packages (edgeR and limma-voom; default parameters) identified differentially expressed genes between cells in the control and DFO treatment.</p> <p>Results:<br>RNA sequencing illustrated transcriptome changes due to iron deficiency including 63 upregulated/81 downregulated genes at day 3, 371 upregulated/780 downregulated genes at day 7, and 342 upregulated/739 downregulated genes at day 14. Importantly, day 14 controls clustered as transcriptional distinct whereas day 14 DFO treated cells clustered with early time points. As expected, genes involved in bone mineralization were suppressed with DFO including <em>Dmp1</em> (logFC: -5.92, p= 5.7e-10) and <em>Phex</em> (logFC: -4.17, p= 5.5e-16). Interestingly, genes such as <em>Ces2e</em>, <em>Gdf15</em>, and <em>Ano3</em>, not previously found associated with osteoblasts, were significantly upregulated after 3 days with DFO (logFC: 5.14, 2.7, and 2.5 respectively).</p> <p>Conclusions:<br>Transcriptomic changes occur even within 3 days of exposure to iron deficiency. Next steps include performing functional enrichment analysis, and validating expression level changes <em>in vitro</em> as well as within <em>in vivo</em> models of CKD-mediated bone loss.</p> <p>Scientific Impact and implications:<br>Iron deficiency is intricately linked to impaired osteoblast function. Understanding the underlying molecular mechanisms could elucidate novel avenues for anabolic bone therapies in CKD.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Shyam Polaconda, Gang Peng, Erica Clinkenbeard, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27813Wearable Submental sEMG Sensors for the Treatment of Dysphagia; A Pilot Study2023-12-11T12:34:48-05:00Albert Y ZhangPeng Ching HsuanKevin BerryGeorgia A Malandraki <p>Swallowing is a complex physiological process that is essential for survival and quality of life. When disrupted, it leads to oropharyngeal dysphagia. This is a common affliction which can have massive implications on health, including an increased risk for pneumonia and malnutrition.</p> <p>Rehabilitative therapy is effective in improving swallowing function, but usually requires clinic visits with a speech language pathologist weekly or multiple times per week. Making treatment more accessible could improve follow-through among the disadvantaged patients with the greatest need for therapy.</p> <p>To address this need, the Purdue I-EaT lab is developing a wearable submental surface electromyography (sEMG) sensor system (i-Phagia) for remote treatment of dysphagia. To evaluate the feasibility of using this device for a single-visit treatment, a pilot pre-post study is being conducted. Participants are evaluated with videofluoroscopic swallowing studies (VFSS) and sEMG before and after a 45-minute treatment session, involving two rehabilitative swallowing exercises, using i-Phagia. Following the post-treatment evaluation, feedback is collected regarding the tolerability of the sensor, including presence of any skin irritation. Outcome variables include normalized mean amplitude, time to peak amplitude of the sEMG signal, and patient satisfaction and safety.</p> <p>As of now, five participants (ages 21, 21, 71, 69, 80) have participated. sEMG analysis was completed in four participants due to data loss for one. Pre-post sEMG analysis of neuromuscular activity showed an increase in normalized amplitude post-treatment in three of four analyzed participants. Four of five participants reported high satisfaction (average score 88/100) and one moderate, and all reported no pain (Wong-Baker pain scale).</p> <p>These results show the feasibility and preliminary effectiveness of using the i-Phagia for in-clinic treatment visits in a small sample of healthy participants. Further research is ongoing to examine the feasibility for use in patients with Parkinson’s disease and for remote use outside of clinic.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Albert Y Zhang, Peng Ching Hsuan, Kevin Berry, Georgia A Malandraki, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27814Clinical Characteristics of Pre-pubescent Patients with Systemic Lupus Erythematosus (SLE)2023-12-11T13:04:46-05:00Ruth ZagalesStacey E. TarvinMartha Rodriguez<p>Background:</p> <p>Systemic Lupus Erythematosus (SLE) is a chronic autoimmune condition that affects multiple organ systems, including cutaneous, renal, neurological, and hematological disorders. Pediatric SLE (pSLE) has a prevalence of 3.3-8.8 cases per 100,000 children. Children with SLE (cSLE) have higher disease severity than adults, but the evidence on cSLE is mostly from pubertal patients, and the reasons for the variation on presentation is unclear. There is limited data on prepubertal SLE, as SLE rarely affects pre-pubescent patients. This study aims to outline the clinical characteristics, disease activity and organ damage of pre-pubescent patients with SLE.</p> <p>Methods:</p> <p>A retrospective study was performed on prospectively collected multi-center data from 2005-2015. Patient data, including race, ethnicity, sex, age of presentation and diagnosis, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and Systemic Lupus International Collaborating Clinics (SLICC) damage index was collected using REDcap.</p> <p>Results:</p> <p>This study included 43 pre-pubescent SLE patients, with an average age at diagnosis of 9.7 years and 10.7 years at the study's start. Organ systems with the highest prevalence rates were musculoskeletal (Arthritis – 69.77%) and cutaneous (Malar rash – 58.14%). The organ systems with the highest involvement frequency, according to the SLICC damage index, were skin (alopecia - 9.3%), ocular (retinal changes/optic atrophy/cataracts - 9.3%), gastrointestinal (pancreatic insufficiency – 4.65%), neuropsychiatric (cognitive impairment – 4.65%), and renal (reduced glomerular filtration rate – 4.65%). Throughout the study, all patients had SLEDAI scores ranging from no activity to high activity, with 55.8% having mild activity, 27.9% having moderate activity, and 14% having high activity.</p> <p>Conclusion:</p> <p>Similar to SLE studies on pediatric populations, our study found that cutaneous, gastrointestinal, and renal manifestations were common. However, we found a high prevalence of damage in prepubertal patients, in particular ocular and cognitive impairment. This highlights the need to prioritize ocular exams and cognitive assessments in patients with prepubertal SLE.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Ruth Zagales, Stacey E. Tarvin, Martha Rodriguez, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27815Sex-Based Differences in LPS-induced Rapid Myocardial Dysfunction2023-12-11T13:16:41-05:00Arris YonilesOlufisayo AnjorinMeghana BhaskaraMeijing Wang<p><strong>Background:</strong> Previous studies have indicated better myocardial responses with preserved cardiac function in female animals compared to males after LPS challenge; however, the mechanisms remain incompletely understood. Our published studies have revealed that TNFa substantially increased in heart tissue and serum following LPS. Females experienced less cardiac dysfunction than males during equivalent dose of TNFa infusion. Therefore, sex-related disparities in myocardial impairment could be due to an indirect/secondary outcome from LPS-induced inflammatory cytokines, like TNFa. To dissect the potential mechanism underlying myocardial reactions between males and females, we aim to determine any sex differences in LPS-caused direct effects on cardiac function using coronary infusion of LPS.</p> <p> </p> <p><strong>Methods:</strong> Isolated hearts from aged-matched adult male and female mice were subjected to LPS infusion via Langendorff after >20-min equilibration (Eq), with left ventricular developed pressure (LVDP) continuously recorded. Dose responsive experiments with LPS at 2.5, 5.0, and 7.5 mg/kg of body weight were performed in male hearts. Significant depression of LVDP (>20% drop) after LPS infusion was considered rapid response to LPS. Female estrous cycle was determined via vaginal smear.</p> <p> </p> <p><strong>Results:</strong> Male hearts infused with 5.0 and 7.5 mg/kg of LPS demonstrated significant depression of LV function. Males also experienced worse outcomes of LV function than females following 5.0 mg/kg of LPS infusion. A trend of earlier response to LPS occurred in male hearts compared to females. However, there were no significant differences in cardiac function between female groups in different estrous phases.</p> <p> </p> <p><strong>Conclusion and Potential Impact</strong>: Our data demonstrates that male hearts exhibit higher sensitivity to LPS-induced rapid cardiac dysfunction compared to females, but estrogen may have little influence on LPS-induced rapid functional depression. The insight from our data can be used to better understand the differences between male and female outcomes to cardiac pathologies and insult.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Arris Yoniles, Olufisayo Anjorin, Meghana Bhaskara, Meijing Wang, MD, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27817Identifying Socio-Demographic and Behavioral Predictors of Prolonged Hospital Stay in an Urban Hospital in Northwest Indiana 2023-12-11T13:32:16-05:00Michael YallourakisEric GonsiorowskiBaraka MuvukaJonathan E. Guerrero<p><strong>Background:</strong> Hospital length of stay (LOS) is a crucial metric that impacts patient outcomes, healthcare resource utilization, and financial burden. In 2019 the CDC reported the average LOS in community hospitals was 5.4 days. Prolonged LOS is associated with an increased risk of hospital-acquired infections, decreased hospital bed availability limiting patient access to care, and cognitive impairment, particularly among the elderly. This indicates the importance of addressing LOS as a healthcare priority. This study examined the relationship between LOS and social determinants of health (SDOH), patient demographics, health behaviors, and health outcomes as part of a long-term Community Based Participatory Research partnership between IUSM-NW and St. Mary Medical Center (SMMC).</p> <p><strong>Methods:</strong> This retrospective study analyzed EPIC™-generated data for adult inpatient visits at an urban hospital in Northwest Indiana from January 2021 to March 2023. Data analysis was performed using SPSS 28.0, consisting of descriptive statistics, bivariate analysis (One-way ANOVA, Independent T-tests, Kruskal Wallis H; p<0.05), and Simple Linear Regression. This study was granted an exemption by the Indiana University Human Research Protection Program (IRB #14040).</p> <p><strong>Results:</strong> The sample comprised of 10,916 predominantly white (77.7%) patients with a median age of 65 (IQR=22) and a median LOS of 4 days (IQR= 5). Bivariate analysis revealed LOS was significantly associated with age (p<0.001), race (p<0.033), sex (p<0.012), insurance type (p<0.001), physical inactivity (p<0.001), and smoking tobacco (p<0.001). After controlling for all factors in the multivariate analysis, age (p<0.020), physical inactivity (p<0.013), and insurance type (p<0.013) retained their significance.</p> <p><strong>Conclusions: </strong>These findings highlight the significance of demographic, behavioral, and social factors in relation to hospital LOS. Understanding these factors holds immense potential to guide the development of targeted interventions and healthcare strategies to optimize patient care and reduce LOS.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Michael Yallourakis, Eric Gonsiorowski, Baraka Muvuka, Jonathan E. Guerrero, PharmDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27820Familial Alzheimer’s Disease Mutation PSEN2 Exacerbates Toxoplasma gondii-mediated Human Blood-Brain Barrier Damage 2023-12-11T13:37:36-05:00William Luke WilsonAbigail BittersAngela ChamberlainJason HughesScott CanfieldAmérico H. López-Yglesias<p><strong>Background and Hypothesis</strong></p> <p><em>Toxoplasma</em> <em>gondii</em> is an obligate intracellular parasite that infects one-third of the global population. <em>T</em>. <em>gondii</em> transmission to humans primarily occurs from the consumption of contaminated meats, water, or produce. Unfortunately, <em>T</em>. <em>gondii</em> will evade the host clearance, allowing it to cross the blood-brain barrier (BBB), infecting neurons where it transitions into slow-growing cysts, leading to a life-long chronic infection. Recently, studies have suggested that <em>T</em>. <em>gondii</em> infection may exacerbate the decline of cognitive function. The BBB is critical for restricting neurotoxic blood-derived products, leukocytes, and pathogens from entering the brain. Studies have shown that BBB dysfunction and damage to the barrier integrity may also contribute to cognitive impairment. Alzheimer’s disease (AD), the most common form of dementia, is a progressive neurodegenerative disease and its neuropathology is associated with b-amyloid plaques. Familial Alzheimer’s Disease is associated with the proteins, presenilin-1 and presenilin-2, encoded by <em>PSEN1 and PSEN2</em>. Mutations in these two genes contribute to early onset AD. Furthermore, dementia has been linked with an increased breakdown of the BBB. Therefore, we hypothesized that <em>T</em>. <em>gondii</em> infection will exacerbate barrier damage and dysfunction in brain microvascular endothelial cells (BMECs) containing familial AD mutations compared to healthy controls.</p> <p><strong>Experimental Design</strong></p> <p>To test our hypothesis, we infected human induced pluripotent stem cell (iPSC)-derived BMECs, which display near <em>in vivo </em>like BBB properties, containing the familial AD <em>PSEN2</em> mutation or healthy controls with <em>T</em>. <em>gondii. </em></p> <p><strong>Results</strong></p> <p>Using immunofluorescence and transendothelial electrical resistance, our results show that BMECs containing the <em>PSEN2</em> mutation have a quicker onset of barrier damage, but we observed no difference in the loss of tight junctions ZO-1, Occludin, and Claudin-5 compared to healthy controls after infection.</p> <p><strong>Potential Impact</strong></p> <p>These data suggest that a <em>T. gondii</em> infection can exacerbate the breakdown of the BBB in patients with the <em>PSEN2</em> mutation, worsening the prognosis of familial AD patients.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 William Luke Wilson, Abigail Bitters, Angela Chamberlain, Jason Hughes, Scott Canfield, Américo H. López-Yglesias, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27821“There’s Healing in Music”: Veteran Perceptions of Music Interventions for Their Chronic Musculoskeletal Pain2023-12-11T13:45:29-05:00Claire WhalenK. Maya StoryMatthew J. Bair<p><strong>Background/Objective:</strong> For veterans suffering from chronic musculoskeletal pain, finding alternative treatments to analgesics is critical for safer, more effective pain management. While music interventions have shown promise for acute pain, their acceptability for chronic pain and telehealth delivery needs more rigorous examination.</p> <p><strong>Methods:</strong> The Feasibility and Acceptability of Music Imagery and Listening Interventions for Analgesia (FAMILIA) study randomized 60 veterans with chronic musculoskeletal pain to receive usual care, telehealth music listening (ML), or telehealth music imagery (MI). ML involved independent listening to songs of each participant’s choosing, while MI consisted of one-on-one music therapist-led sessions combining ML, imagery, and verbal processing. To complement quantitative analysis of patient-reported outcomes, qualitative interviews of participants were conducted to understand perceived benefits, acceptability, barriers, and facilitators of study interventions. We analyzed 15 interviews using thematic analysis to assess acceptability of the music interventions.</p> <p> </p> <p><strong>Results: </strong>All interviewees perceived mental-emotional benefits and almost all experienced physical pain relief during their music listening or therapy sessions. However, many noted that the pain relief was short term, and for some veterans randomized to ML, certain songs evoked negative associations. Participants also benefited from study participation and its formal structure, in contrast to their prior informal music listening experiences. Planned study activities like participant check-ins with staff and interactions with therapists fostered a deeper understanding of how music can be therapeutic and increased veterans’ confidence in their own ability to use music therapeutically. Study acceptability was further evidenced by interviewees’ intention to continue using music listening and imagery techniques after study completion and their strong support for expanding access to music interventions to other veterans.</p> <p><strong>Conclusion/Implications:</strong> The FAMILIA study not only supports telehealth music interventions as acceptable treatments for chronic musculoskeletal pain, but the reported physical pain and mental-emotional benefits necessitate a larger, fully powered study.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Claire Whalen, K. Maya Story, Matthew J. Bair, MS, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27823Ethanol Induces Blood Brain Barrier Dysfunction in Healthy and Familial Alzheimer’s Blood Brain Barrier Models2023-12-11T14:05:26-05:00Abby M. WetzelKameron T. BellJason M. HughesScott G. Canfield<p><strong>Background/Objective:</strong></p> <p>The blood brain barrier (BBB) is a highly selective semipermeable membrane between the blood and brain. Active efflux transporters such as PGP, MRP-1, and BCRP and localized tight junction proteins ensure barrier integrity. Interestingly, both alcohol consumption and Alzheimer’s disease (AD) suppress barrier functions independently. Furthermore, alcohol use can lead to or worsened neurodegenerative disorders, including AD. In this study, human stem-cell derived healthy and AD BBB models with near <em>in vivo</em> properties are used to investigate the effects of alcohol on critical BBB properties such as barrier tightness and efflux transporter activity.</p> <p><strong>Methods:</strong></p> <p>Induced pluripotent stem cells (iPSCs) from healthy (IMR90) and Familial Alzheimer’s (APP, PSEN1, PSEN2) cell lines were differentiated into brain microvascular endothelial cells (BMECs). BMECs were treated with varying ethanol concentrations (5, 25, 50, and 100 mM) for one hour. Following ethanol treatment several barrier properties were assessed: trans-endothelial electrical resistance (TEER), sodium fluorescein permeability, tight junction localization, and efflux transporter activity.</p> <p><strong>Results:</strong></p> <p>Moderate to severe ethanol concentrations (25 mM and 50 mM) reduced TEER and delocalized tight junctions in healthy and AD-derived BMECs, indicating a disruption in barrier integrity. AD-derived BMEC cell lines also show an increased susceptibility to ethanol-induced barrier dysregulation at lower concentrations of ethanol (5 mM). Interestingly, our preliminary data shows that ethanol exposure seems to reduce BCRP efflux transporter activity in APP and PSEN1 AD cell lines.</p> <p><strong>Conclusion and Scientific Impact and Implications:</strong></p> <p>This study is novel in elucidating the enhanced disruption of BBB properties in familial AD-derived BMEC cell lines following ethanol exposure and provides insight into the potential harm of alcohol consumption in the development and/or exacerbation of BBB dysfunction in Alzheimer’s disease. Further studies will also unveil the possibility of ethanol-induced reduction of BCRP efflux transporter activity in APP and PSEN1 AD.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Abby M. Wetzel, Kameron T. Bell, Jason M. Hughes, Scott G. Canfield, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27824Medicaid Reimbursement for Community Health Workers: A Comparative State Policy Analysis with Implications for Indiana2023-12-11T14:11:06-05:00Kylie WertzJulia AmstutzMichael ScanlonDebra K. Litzelman<p><strong>Background</strong>: Community health workers (CHWs) promote health education, address social determinants of health, and bridge the gap between healthcare systems and underserved populations, but the lack of sustainable funding remains a challenge to greater CHW utilization. Medicaid reimbursement has been identified as a promising mechanism to fund CHWs, however, state policies vary widely. A comparative policy analysis can guide future reimbursement strategies.</p> <p><strong>Methods</strong>: We conducted a comparative policy analysis of Medicaid reimbursement for CHWs. State government websites and legal databases were searched utilizing keyword search terms related to CHWs and Medicaid reimbursement. We identified and analyzed relevant statutes, regulations, and administrative codes for reimbursement mechanism, rates, supervision, certification, and scope of practice.</p> <p><strong>Results</strong>: 26 states currently reimburse CHWs through Medicaid; 3 states started reimbursement in the last six months. 16 states authorize payment through State Plan Amendments (SPAs), 3 use Section 1115 demonstration waivers, 10 use Medicaid managed care organization contracts, and 4 use blended strategies. 13 states require certification and supervision for reimbursement, although the supervising licensed professional can vary. The scope of practice of CHW also varies between states. There is a large range for reimbursement rates; for example, billing code 98960 currently used by 14 states varies from $9.70 in Indiana to $55.25 in Arizona for a 30 minute visit.</p> <p><strong>Policy Implications</strong>: This study can inform sustainable reimbursement models through Medicaid for CHWs in Indiana and other states. An SPA may be the most expedient way for Indiana to increase reimbursement for CHWs, but its narrowness and inflexibility could hinder CHWs' positive impact. The variety of strategies currently in use demonstrates that there is no single path to sustainable financing. Protocols for a set of scoping reviews will result from this comparative analysis for more in-depth investigations of key peer-reviewed and grey literature.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Kylie Wertz, Julia Amstutz, Michael Scanlon, Debra K. Litzelman, MD, MACPhttps://journals.iupui.edu/index.php/IMPRS/article/view/27826Investigating the Modulating Effects of Tirzepatide on NAFLD/NASH Progression Using 3D Human Liver Organoids2023-12-11T16:15:07-05:00Barry WeiThi M.U. LeEvan J. `CatronRobert P. PassarelliPing LiWenjun ZhangBurcin Ekser<p><strong>Background:</strong> Nonalcoholic fatty liver disease (NAFLD) is a disease characterized by the accumulation of lipids in the liver that ultimately progresses to nonalcoholic steatohepatitis (NASH) and cirrhosis. Currently, there is no known FDA-approved treatment for NASH. Tirzepatide (brand name Mounjaro), a glucagon-like peptide 1 (GLP-1) agonist, has been hypothesized to have potential effects in reversing NAFLD/NASH progression and restoring liver function. However, this hypothesis remains untested in current literature. The aim of this study is to use 3D human liver organoids (3D-HLOs) as an <em>ex vivo</em> model system to determine the potential effects of tirzepatide on the progression of NAFLD/NASH.</p> <p> </p> <p><strong>Methods:</strong> 3D-HLOs were constructed by incorporating 5 major human hepatic cell types isolated from NAFLD livers, including hepatocytes, hepatic stellate cells, liver endothelial cells, cholangiocytes, and Kupffer cells. NAFLD 3D-HLOs were maintained in the hepatocyte medium supplemented with 50mM free fatty acid (FFA) only (control group) or FFA+tirzepatide (100nM, 200nM, or 500 nM) for 14 days. By the end of the treatment, 3D-HLOs were subjected to BODIPY493/503 staining to determine lipid droplet accumulation. Immunofluorescence staining and confocal microscopy analysis were performed to confirm hepatocyte function (ALBUMIN) and fibrosis (COL1A1). qPCR was performed to determine the relative expression markers of hepatocyte function (ALBUMIN, HNF4A), angiogenesis (PECAM-1, VCAM-1, ICAM-1), and fibrosis (ACTA2, COL1A1).</p> <p><strong><u> </u></strong></p> <p><strong>Results:</strong> BODIPY 493/503 revealed no significant difference in lipid deposition between 3D-HLOs in all treatment groups. Mean immunofluorescence staining intensity for albumin in controls, 100nM, 200nM, and 500nM tirzepatide were 154.4, 181.4, 221.1, and 236.4, respectively (p>0.05). Dose-dependent quadratic regression revealed a strong correlation between dose and albumin fluorescence intensity (R<sup>2</sup> = 0.963). qRT-PCR analysis revealed that tirzepatide treatment did not significantly alter transcriptional levels of ALB, HNFA4, ACTA2, PECAM-1, VCAM-1, and ICAM-1 compared to the control group.</p> <p> </p> <p><strong>Conclusion</strong>: Although there is no statistically significant difference in liver cell function markers at different tirzepatide dosages in the setting of NAFLD/NASH, the highest dose of tirzepatide improved ALB expression despite ongoing FFA exposure, indicating a potential hyperbolic relationship between tirzepatide concentration and albumin production. Future investigation with altered treatment duration and dosage will elucidate whether there are any direct modulating effects of tirzepatide on NAFLD/NASH progression.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Barry Wei, Thi M.U. Le, Evan J. `Catron, Robert P. Passarelli, Ping Li, Wenjun Zhang, MD, PhD, Burcin Ekser, MD, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27827MR1/MAIT Cell Axis Impacts Innate Immunity and Synaptic Proteins in 5XFAD Mice2023-12-11T16:22:14-05:00Jalyn WarrenSeason JohnsonSamantha AckleyReham AfifiRashmi ShrinivasanRandy R. Brutkiewicz<p><strong>Background:</strong></p> <p>Amyloid beta (Aβ)-induced synaptic dysfunction and inflammation are features of Alzheimer’s disease (AD). One contributor to inflammation is mucosal-associated invariant T (MAIT) cells, an innate T cell that recognizes antigens presented by the MR1 molecule. Previously, we found increased MR1 expression in microglia near plaques and the loss of MR1/MAIT cell axis slowed the progression of Aβ pathology. This study aimed to determine contributions of the MR1/MAIT cell axis to immunity and synaptic proteins in the 5XFAD AD model mouse.</p> <p><strong>Methods:</strong></p> <p>We crossed 5XFAD mice with MR1-deficient mice (which lack MR1 and MAIT cells). At 2-, 4-, 6-, and 8-months of age, hippocampal and cortical brain tissue from wild-type, MR1KO, 5XFAD, and 5XFAD/MR1KO mice were analyzed by Western blot. Protein levels were analyzed with antibodies against GFAP (astrocytes), complement C3, and postsynaptic density protein (PSD)95. Additionally, Novel Object Recognition, Open Field, and Barnes Maze behavioral tests were performed in the 5XFAD mice to measure memory deficits.</p> <p><strong>Results:</strong></p> <p>Region-specific results were obtained for the hippocampus and cortex. The expression levels of PSD95 and C3 were significantly upregulated in the hippocampus of 5XFAD/MR1KO compared to 5XFAD mice at 6-8 months of age; in the cortex, GFAP levels were also significantly increased in 5XFAD/MR1KO mice. Finally, compared to wildtype C57BL/6 mice, 5XFAD mice showed memory deficits.</p> <p><strong>Conclusions and Potential Impact:</strong></p> <p>Approximately 6.7 million Americans are living with AD. This number is expected to double by 2050. Without any currently demonstrated therapy against AD, there is a need for therapeutic target(s) as part of novel treatment paradigms. Our results demonstrate an impact of the MR1/MAIT cell axis on postsynaptic proteins and consequent AD pathology. Thus, understanding the contribution of this axis could help reveal the role of innate immunity in AD and potentially serve as a future therapeutic target in AD patients.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Jalyn Warren, Season Johnson, Samantha Ackley, Reham Afifi, Rashmi Shrinivasan, Randy R. Brutkiewicz, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27840Development of a Community Informed Approach for Implementing Support Network Trainings for Children with Autism Spectrum Disorder in Western Kenya2023-12-13T04:25:59-05:00Geneva BaumbergerSaina ChelagatRebecca McNally KeehnAnita RuttoMegan S. McHenryMandy Rispoli<p>Background:<br>Autism spectrum disorder (ASD) impacts a large global community, with a prevalence of nearly 1 in 100 children. However, little is known about the educational experience of children with ASD and other neurodevelopmental disorders (NDD) in low- and middle-income countries (LMICs). Guidance from local communities is essential when developing a cultural inquiry into this educational landscape. Our project objective was to evaluate community perspectives on ASD and areas of development for future support network trainings.</p> <p>Methods:<br>This qualitative study was performed within the Academic Model Providing Access to Healthcare (AMPATH) program in Eldoret, Kenya. Using group discussions, this approach engaged stakeholders from three areas: medical personnel, educators, and caregivers/families. Kenyan professionals in child psychiatry, occupational therapy, and special education guided discussion and led the recruitment of key informants for interviews. Within this qualitative analysis, brief thematic analysis of dialogue elucidated key themes.</p> <p>Results:<br>Four focus groups were held, with 87 total participants (group size = 12-29). Four main themes were identified in the data: beliefs about causes, treatment options, barriers to education, and a need for community advocacy. Advocacy was a major focus of discussions, due to a sentiment of fragmentation and poor acceptance from the community. Stigmatization carried over into local<br>beliefs about causes of ASD, which included poor nutrition, witchcraft, and genetics. Finding resources to access education and therapy was a challenge, especially for families in rural settings. These viewpoints informed study protocol adaptation by expanding recruitment to include community-based service providers and staff from additional schools, and integrating themes into interview questions.</p> <p>Conclusion:<br>This project prioritized dialogue with stakeholders to gain insights to inform the development of a cultural inquiry into the special education landscape in western Kenya. Themes elucidated from this project provided critical feedback to inform future study protocol and an expanded recruitment plan.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Geneva Baumberger, Saina Chelagat, Rebecca McNally Keehn, Anita Rutto, Megan S. McHenry, MD, Mandy Rispolihttps://journals.iupui.edu/index.php/IMPRS/article/view/27841Factors Affecting General Surgery Intern Wellness: A Qualitative Study2023-12-13T04:42:00-05:00Payton BearMadeline BlackwellDimitrios Stefanidis<p>Background:<br>Surgical training is demanding and presents numerous challenges to new interns including long working hours that can threaten their well-being. The factors affecting their well-being as reported by interns themselves, are however, poorly understood. This qualitative study aimed to determine the factors contributing to the wellness of general surgery interns, and identify potential areas that could benefit from intervention and policy reform.</p> <p>Methods:<br>A comprehensive scoping review of the literature on resident wellness was initially performed, using "resident" and "wellness" as search criteria on PubMed, and encompassing articles published from 2013 onward. The results of this review were used for the development of an interview guide for in-person focus groups. General surgery interns at Indiana University participated in focus groups that were recorded and transcribed. Two coders coded the transcript independently to develop a code book. Thematic analysis was conducted using a constructivist grounded theory methodology to determine emergent themes.</p> <p>Results:<br>Ten surgical interns participated in the focus groups. Qualitative analysis revealed five predominant themes that impact intern wellness: Lack of respect, inadequate facilities and resources, lack of fulfillment, work overload, and poor communication.</p> <p>Conclusions:<br>The themes identified reveal numerous factors that impact intern wellness beyond working hours and pay and provide targets for interventions that can address them. Our results suggest that “one-size fits all” wellness solutions are unlikely to address the specific challenges faced by surgical trainees; multifaceted interventions are required to enhance intern well-being. Future research should focus on the development and implementation of targeted strategies to address these identified issues.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Payton Bear, Madeline Blackwell, Dimitrios Stefanidis, MD, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27842Clinical Utility of Dupilumab for the Treatment of Eosinophilic Esophagitis in Pediatric Patients2023-12-13T04:51:58-05:00Alexa BeckerParoma Bose<p>Background:<br>Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus characterized by symptoms of esophageal dysfunction and 15 or more eosinophils per high-powered field (HPF) on esophageal biopsy. Treatment options for EoE include proton pump inhibitors (PPIs), topical corticosteroids (TCS), dietary elimination, and dupilumab. Dupilumab is monoclonal antibody against IL-4 and IL-13 administered subcutaneously and was granted FDA approval for EoE in adults and adolescents recently in 2022. Outcomes of real-world, clinical use of dupilumab for EoE remains unknown.</p> <p>Objectives:<br>To observe outcomes in pediatric patients with EoE treated with dupilumab.</p> <p>Methods:<br>A retrospective cohort study of pediatric patients prescribed dupilumab for EoE was conducted. Medical records were reviewed for demographic and clinical information as well as endoscopic and histologic findings before and after dupilumab treatment.</p> <p>Results:<br>A total of 28 patients were included (mean age 15y, 71.4% male). Mean baseline maximum eosinophils/HPF was 48 ± 41. 75% of patients were treated with combination therapy of EoE with diet elimination, PPIs, or TCS prior to being prescribed dupilumab. Prior authorization for dupilumab was required in 85.7% of cases. Ten patients had follow-up endoscopy with biopsy after starting dupilumab, and among these patients the mean maximum eosinophils/HPF with dupilumab significantly improved from 44 ± 37 to 13 ± 15 (p=0.027). Among 12 patients who had follow up clinic visits, two patients reported pain or swelling at injection sites, but no other<br>adverse events were reported</p> <p>Conclusions:<br>Dupilumab significantly improves histologic findings of EoE and is well tolerated among pediatric patients. We hope for continued monitoring of these patients to understand the clinical utility of dupilumab for EoE over time.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Alexa Becker, Paroma Bose, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27843Prevalence of Positive Urine Drug Screen for Fentanyl and its Analogs in Indianapolis2023-12-13T05:00:03-05:00Jennifer BeckmanElizabeth MastDavid ShepherdMichelle K. ZimmermanRejwi Dahal<p>Background and Hypothesis: IU Health Pathology Laboratory (IUHPL) recently added qualitative fentanyl screening to its test menu. However, fentanyl screening is not currently part of the urine drugs of abuse (DAU) panel which includes amphetamine, barbiturates,<br>benzodiazepines, buprenorphine, cannabinoids, methadone, cocaine, opiates, oxycodone, and phencyclidine. Since fentanyl screen is a standalone test, we were interested in determining how often specimens had this ordered in conjunction with the DAU, as we suspected not all of them did. Our hypothesis was that positive urine drug screens may also be positive for fentanyl/fentanyl analogs.</p> <p>Project Methods: Urine specimens sent for routine drug screens at IU Health Arnett, Ball, Bloomington, and IUHPL between June and mid-July 2023 were subjected to fentanyl screening. Specimen that screened positive were confirmed by LC-MS/MS for presence of<br>fentanyl and norfentanyl. Additionally, specimens were tested for 4ANPP (fentanyl precursor) and xylazine; if they were positive for either, they were sent to an outside laboratory to ascertain if other fentanyl analogs or designer opioids were present.</p> <p>Results: Of the 1,893 DAU specimens received, 51.2% were positive for at least one drug class. Only 28 had an associated fentanyl screen order. Cannabinoids represented the most prevalent drug class with a 26.7% positivity rate. Only 1,724 samples were available to screen for fentanyl as part of this study. Of these, 214 specimens were positive for fentanyl, with a positivity screen rate of 12.4%. Confirmatory testing by LC-MS/MS indicated 206 of the 214 were true positives.</p> <p>Conclusion and Impact: These results highlight the need for fentanyl testing and continued clinician education to increase awareness about the inability of standard urine drug screens to detect fentanyl. Dialogue between patients and clinicians would potentially decrease overdoses and/or result in more treatment referrals. Additionally, integrating fentanyl screening into the DAU panel will facilitate qualitative fentanyl testing.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Jennifer Beckman, Elizabeth Mast, David Shepherd, Michelle K. Zimmerman, PhD, Rejwi Dahal, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27844Exploring Differentiation and TEAD Inhibition in NF2-Knockdown NES Cells2023-12-13T05:14:33-05:00Sidrah BadarNoah BurketJignesh Tailor<p>Background: The <em>NF2</em> gene is a tumor suppressor encoding gene on chromosome 22 that is a known regulator of the Hippo pathway. When the mammalian version of the pathway is inactive, such as with a loss of NF2, downstream proteins YAP/TAZ remain unphosphorylated, enter the nucleus to form a complex with TEAD 1/2/3/4, and begin transcription. Hyperactivation of the<br>YAP/TAZ-TEAD complex has been observed in many cancers, allowing for targeting with TEAD inhibitors. Here, we assess how the loss of NF2 in human neuroepithelial stem (NES) cells affect their differentiational development. We also seek to understand the effects of TEAD inhibition on wildtype (WT) and NF2-knockdown NES cells.</p> <p>Materials and Methods: <em>Differentiation</em>. WT and NF2-knockdown cells were grown in media without growth factors to differentiate them. TEAD <em>Inhibition</em>. Non-differentiating and differentiating WT and NF2-knockdown cells were treated with TEAD Inhibitor 690 (TEADi). During both conditions, cells were harvested at 5 points throughout the growth period.</p> <p>Results: Decreased NF2 in cells promoted retention of an earlier cell morphology compared to WT, which appeared to develop neuronal features, such as axons. WT cells exhibited elevated expression of genes characteristic of NES differentiation when compared to NF2-knockdown cells. Following the addition of TEADi, cell culture imaging revealed seemingly increased cell death in WT cell populations compared to NF2-knockdown cells. Interestingly, differentiating NF2-knockdown cells adhere to one another to form clusters, but with TEADi, these clusters are formed to a much lesser extent.</p> <p>Conclusion: Although more experimentation is needed, these are early steps in demonstrating how NF2 loss appears to halt the differentiation of NES cells. Additionally, TEAD inhibition seems to reduce the clustering seen in differentiating NF2-knockdown cells; however, experimental concentrations need to be explored in the future. Further work is needed to understand the effects of TEAD inhibition on NF2-knockdown cells.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Sidrah Badar, Noah Burket, Jignesh Tailor, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27845Comparison of Visual Field Fluctuation Between Myopic and Emmetropic Glaucoma Patients2023-12-13T05:29:10-05:00Molly BartenLouis Cantor<p>Background: Conflicting epidemiologic studies suggest that myopia may both increase and decrease the risk of glaucomatous visual field loss. To provide appropriate treatment to glaucoma patients, it is important to detect meaningful changes in the visual field, which requires distinguishing between visual field fluctuation and progression. Visual field fluctuation is defined as the variability between two visual field tests performed on separate days or months on the same eye that cannot be attributed to a pathologic change. We hypothesize that glaucoma patients with myopia will demonstrate more visual field fluctuation compared to emmetropic patients.</p> <p>Methods: Four or more 24-2 or 30-2 Humphrey visual field tests over several visits will be analyzed per patient. Data including the VFI plot, mean deviation, and threshold sensitivity on the glaucoma progression analysis will be collected to measure fluctuation. The sample is divided into two groups: 1. emmetropic glaucoma patients with a spherical equivalent refraction between +2 to -2 diopters and 2. high myopic glaucoma patients with a spherical equivalent refraction over -5 diopters. Bland-Altman plots, Mann-Whitney U tests, Root Mean Square Error (RMSE), intraclass correlation coefficients, and generalized estimating equation models for ordinal data will be used to analyze the collected data.</p> <p>Results: Thus far, 2,979 charts have been reviewed with data collected from 27 emmetropes and myopes who met the inclusion criteria. The recruitment goal is 78 per group and 156 total. Preliminary results for RMSE found a statistically significant p-value for mean deviation (0.0320), and no statistically significant difference for threshold sensitivity (0.5179) and VFI (0.0904).</p> <p>Conclusion and Potential Impact: This ongoing study will help establish if glaucoma patients with high myopia demonstrate greater visual field fluctuation. It is important for clinicians to have this information so that these patients can be examined carefully to prevent misdiagnoses or delayed glaucoma treatment.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Molly Barten, Louis Cantor, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27846Neighborhood Disadvantage and Healthcare Utilization in Pediatric Sickle Cell Patients2023-12-13T05:36:53-05:00Ashley CatanzariteJillian BouckSeethal Jacob<p>Background: Sickle cell disease (SCD) is a complex heritable blood disorder associated with higher acute healthcare utilization further complicated by psychosocial and socioeconomic factors. Other studies have indicated a relationship between neighborhood disadvantage and increased healthcare utilization. We hypothesize that those with greater neighborhood disadvantage will have greater acute healthcare utilization.</p> <p>Methods: Data was collected retrospectively from the electronic medical record between 9/30/2021 and 7/11/2023 for patients followed at Riley Hospital for Children’s Pediatric SCD Clinic who completed a psychosocial needs assessment (PAT). Number of emergency department (ED) visits, hospitalizations, and missed clinic visits were collected from the time the PAT was completed up to 1 year after (or the end of the data collection period). Data regarding area deprivation index (ADI) and childhood opportunity index (COI) were collected utilizing patient home address. Descriptive statistics were performed on all data above, as well as t-tests and chi square tests for univariate analyses.</p> <p>Results: 142 patients completed a PAT during the study period. 88% had a primary care provider documented, and 73% had public insurance. The median state and national ADI (6, 76.5) and COI (2, 2) demonstrated greater neighborhood disadvantage and less childhood opportunity. There was no statistically significant difference between ADI or COI and number of ED encounters or hospitalizations. However, patients who missed 1 or more SCD visits had a higher median state ADI than those who did not miss a visit (7.5 vs 5, p=0.002). Median state COI was also lower in this group than those who did not miss a visit (1 vs 2, p=0.001).</p> <p>Conclusion: Those with higher ADI and lower COI could benefit from more directed support to improve access to preventative care visits. Further analysis accounting for comorbidities (seizures, asthma, depression) could disambiguate a relationship between ADI or COI and acute care utilization.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Ashley Catanzarite, Jillian Bouck, Seethal Jacob, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27847Artificial Intelligence in the Detection of Fatty Liver Disease2023-12-13T05:43:02-05:00Evan J. CatronRobert P. PassarelliDanielle WilmesAlex GriesemerBarry WeiMinh-Uyen T. LePing LiWenjun ZhangJingmei LinPlamen V. MihaylovChandrashekhar A. KubalRichard S. MangusBurcin Ekser<p>Background: The current gold standard for quantification of the fat content of the liver (i.e., nonalcoholic fatty liver disease, NAFLD) is the visual microscopic inspection of liver biopsies by pathologists. Percentage of macrosteatosis (%MaS), used in determining NAFLD diagnosis, is vital in determining the transplant suitability of a donor liver. A major limitation of this method is inevitable human error which causes interobserver variability and overestimation of %MaS which could cause a potential discard of donor livers. We hypothesize that artificial intelligence (AI) can assist pathologists in providing a more objective and accurate measure of %MaS.</p> <p>Methods: Our literature review identified HALO (image analysis) and U-Net (deep-learning) as AI programs currently available for high-accuracy %MaS calculation in liver biopsies. We compared the pathologist-reported %MaS from de-novo liver transplant (LT) biopsy samples taken 2h post-reperfusion to the %MaS calculated by HALO and/or U-Net (Fig. 1). 250 patients had undergone de novo LT at Indiana University between 2019-2020, and 211 of these patients had sufficient data (liver enzyme tests, biopsy results) to be included. Each biopsy sample was digitized into 5 random non-overlapping tiles at 20x magnification using a Leica microscope. Early allograft dysfunction (EAD) is defined by the presence of at least one of the following: (i) INR >1.6 on postoperative day (POD) 7, (ii) total bilirubin >10 mg/dL on POD7, or (iii) AST/ALT >2000 IU/L within the first 7 days following LT.</p> <p>Results: Our literature review identified that both HALO and U-Net estimated the %MaS in liver allograft biopsies significantly lower than pathologists' estimation (Fig.1). Of 211 included patients, 46 (21.8%) had EAD. In this ongoing project, we found U-Net to have a 97.3% training accuracy with eight epochs (2000 biopsy images each). Tiles from the first ten patients are being analyzed by HALO and/or U-Net to calculate an average %MaS for each patient. These calculations will be compared to the %MaS estimation made by pathologists.</p> <p>Conclusions: The rapidly evolving field of AI is emerging as a promising method in the quantification of the fat content of the liver with increased accuracy. AI will therefore help pathologists and transplant surgeons to determine liver transplant viability and better predict EAD in transplant patients.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Evan J. Catron, Robert P. Passarelli, Danielle Wilmes, Alex Griesemer, Barry Wei, Minh-Uyen T. Le, Ping Li, Wenjun Zhang, Jingmei Lin, Plamen V. Mihaylov, Chandrashekhar A. Kubal, Richard S. Mangus, Burcin Ekser, MD, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27848Ineffectiveness of mitoTEMPO on Cardiomyocyte S-phase Activity in TNNI3K-expressing Mice2023-12-13T05:55:03-05:00Elias ChahoudSean ReuterLoren Field<p>Background and Hypothesis: The limited regenerative capacity of the mammalian adult myocardium is a significant roadblock for therapeutic approaches in cardiovascular disease. Cell cycle arrest following S-phase is widely considered a primary contributor to the reduced proliferative capacity of adult cardiomyocytes. Recently, expression of troponin I-interacting kinase (Tnni3k) was shown to increase cardiomyocyte S-phase activity in mice. Tnni3k was previously shown to enhance ROS formation and adverse cardiac remodeling following injury. Our primary hypothesis was that TNNI3K-induced cardiomyocyte DNA synthesis resulted from enhanced ROS signaling. To test this, cardiomyocyte S-phase activity in TNNI3K-expressing mice was compared between those treated with the ROS scavenging agent mitoTEMPO and untreated mice.</p> <p>Project Methods: Transgenic mice expressing TNNI3K were subjected to 14 days infusion with mitoTEMPO (experimental group) or vehicle (control group). The mice were also subjected to 14 days infusion with bromodeoxyuridine (BrdU) to identify DNA synthesis during S-phase (all mice carried a cardiomyocyte-restricted nuclear-localized transgenic reporter to aid in cardiomyocyte nuclei identification). The proportion of cardiomyocytes in S-phase was determined and mean S-phase activity was compared between treatment groups. Ploidy analysis was also conducted to determine if cardiomyocytes completing S-phase progressed through karyokinesis.</p> <p>Results: The percentage of cardiomyocytes in S-phase in the control and mitoTEMPO treated group were 0.819% ± 0.163% and 0.855% ± 0.138%, respectively (mean ± SEM, p=0.873). Ploidy analysis revealed no overt difference in DNA content in S-phase-positive cardiomyocyte nuclei between the groups. Hence, we have shown that there is no appreciable difference in cell cycle induction or progression in cardiomyocytes from control vs. mitoTEMPO treated mice expressing TNNI3K.</p> <p>Conclusion and Potential Impact: These data suggest that (a) TNNI3K-induced cardiomyocyte S-phase activity is not secondary to elevated ROS activity, and (b) reduction of ROS activity does not relax the cell cycle block between S-phase and karyokinesis in adult<br>cardiomyocytes.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Elias Chahoud, Sean Reuter, Loren Field, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27849Neurovascular Conditions and Associated Socio-Demographic and Behavioral Factors in an Urban Hospital in Northwest Indiana2023-12-13T06:03:56-05:00Brendan JonesBrianna ChandlerKelly DeMichaelBaraka MuvukaJonathan GuerreroKyle Gosporadek<p>Background: Brain health equity remains an underexplored research area despite high prevalence of neurovascular conditions and related health impacts. This study examined the associations between socio-demographic, behavioral factors, and hospital admissions for neurovascular-related morbidity in an urban underserved community. It is part of a multi-phased Community-Based Participatory Research (CBPR) partnership between Indiana University School of Medicine-Northwest and St. Mary Medical Center (SMMC) to examine the prevalence, distribution, and relationships between social determinants of health (SDOH), demographics, health behaviors, and health outcomes in Northwest Indiana.</p> <p>Methods: This retrospective study analyzed a limited dataset generated by SMMC from EPIC™ with SDOH, demographic, behavioral and health outcomes data for adult inpatient visits from January 2021 to March 2023. Neurovascular admission was determined by ICD-10 Codes I67-69. Data analysis was conducted in SPSS 29.0 using descriptive statistics (i.e., frequencies and central tendency), bivariate analysis (Chi-square; p<0.05), and multivariate analysis (binary logistic regression; p<0.05). This study received exemption from Indiana University Human Research Protection Program (IRB #14040).</p> <p>Results: There were 1,489 participants included in this study. The majority were white (77.7%), older adults (67 ± 21.5) and publicly insured (77.8%). The bivariate analysis demonstrated significant relationships between admission for neurovascular conditions and age group (p<0.001), veteran status (p<0.001), insurance type (p<0.037), and physical activity (p<0.001). After adjusting for these factors in multivariate analysis, age group (p< 0.003) and physical inactivity (p<0.008) were significantly associated with admission for neurovascular conditions.</p> <p>Conclusion: Understanding how SDOH and behavioral factors influence neurovascular admissions and inequities in urban settings will enhance collaborative efforts to develop, implement, and evaluate evidence-based interventions. The subsequent CBPR phases will utilize these findings to explore how socioeconomic status affects these patients’ ability to seek emergent and/or surgical care. This will enable implementation of strategies that better account for SDOH in patient care.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Brendan Jones, Brianna Chandler, Kelly DeMichael, Baraka Muvuka, Jonathan Guerrero, Kyle Gosporadek, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27850Inhibition of HSF1 as a Mechanism for Overcoming Hsp90 Treatment Resistance2023-12-13T06:12:24-05:00Zachary ChastainImade WilliamsVrushabh UlhaskumarJohn WangHaddie DeHartHaimanti RayRichard L. Carpenter<p>Hsp90 inhibitors have been attempted as a targeted therapy with poor results. Despite numerous clinical trials, there are currently no FDA approved Hsp90 inhibitors available. It is known that Hsp90 sequesters HSF1 in the cytoplasm to suppress HSF1 activity, an oncogenic transcription factor. We hypothesize that HSF1 activation in response to Hsp90 inhibition is a significant reason that previous Hsp90 inhibitors have failed. Once released, HSF1 enters the nucleus and drives expression of many processes that promote the initiation and progression of tumors. This hypothesis was tested by evaluating the response of cancer cells to Hsp90 inhibition with or without combined inhibition of HSF1, thereby removing HSF1 activity as a consequence of Hsp90 inhibition. We observed synergy between Hsp90 inhibition (17-DMAG) and HSF1 inhibition (KRIBB11) from calculation of combination index in ovarian cancer cells (OVCAR8) and breast cancer cells (BT474). This synergy observed in cell viability assays were further reinforced in spheroid formation and clonogenic growth assays where the combination of these inhibitors had a greater effect than either treatment alone. These results further support the hypothesis that Hsp90 inhibition efficacy is mitigated by increased HSF1 activity and that HSF1 inhibitors synergize with Hsp90 inhibitors to improve their efficacy.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Zachary Chastain, Imade Williams, Vrushabh Ulhaskumar, John Wang, Haddie DeHart, Haimanti Ray, Richard L. Carpenter, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27851Student Perceptions of Two Preclinical Medical School Exam Feedback Approaches2023-12-13T06:21:45-05:00Elsie GasawayValerie O’Loughlin<p>Background: In medical school, where learning an abundance of information in a short period of time is required, it is necessary that learners receive valuable feedback after summative assessments (i.e., unit exams). First-year medical students at Indiana University School of Medicine (IUSM) begin their education with a course titled Human Structure (HS), followed by Molecules to Cells and Tissues (MCT). Both courses provided different formats for exam feedback, resulting in anecdotal comments about preference and utility of feedback. This study uses qualitative research methods to examine IUSM-Bloomington students’ perceptions of exam feedback formats with respect to their utility and applicability.</p> <p>Methods: Five, second-year IUSM-Bloomington medical students participated in a focus group to discuss their utilization and perceived usefulness of HS and MCT exam feedback. A thematic analysis was used to interpret data from the focus group. This study was deemed exempt by the IU-IRB (19409).</p> <p>Results: The thematic analysis revealed that students’ discussions fell into three categories: logistics, utilization, and mentality. These categories were further broken into themes and subthemes, revealing 13 unique codes. Students spent a substantial amount of time discussing logistics of exam feedback. Barriers to utilization of exam feedback included a lack of information provided at the feedback sessions and a lack of time in the schedule available for feedback sessions. Students preferred MCT approach to exam feedback, however they recognized HS course logistics may prevent similar adoption. Students had small suggestions on how to improve feedback in both courses.</p> <p>Conclusions/Implications: The data suggest students would benefit from small changes in how first-year medical school courses at IUSM provide exam feedback. Improvements could include extending the time of exam review sessions, incorporating a discussion on commonly missed exam concepts, providing answer explanations for incorrect and correct answers, and transitioning statewide reviews to be campus led.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Elsie Gasaway, Valerie O’Loughlin, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27852Health Disparities in Acidosis Risks2023-12-13T06:26:59-05:00Allison GatzChenxi XiongXiaochun LiMichael EadonJing Su<p>Background: Health disparities in acidosis risk are entangled with a range of factors including clinical conditions, genomic traits, and demographic features. Current clinical guidelines and policies on the safety of metformin have not yet taken holistic considerations of health disparities and other risk factors. The All of Us (AoU) research dataset provides comprehensive information including longitudinal real-world data for diseases and treatments, genetic data, and surveys for social determinants of health, with a focus on minority groups and the underserved population. This study leverages the AoU data to understand the health disparities in acidosis risk and provides real-world evidence to support clinical decisions.</p> <p>Methods: A case-control design was used to identify risk factors associated with emergent acidosis events, with a 1:4 matching using propensity scores specified by enrollment date, number of diagnoses, and length of medical history. Risk factors were sex, age, race, ethnicity, metformin use, Charlson comorbidities, and insurance status. Adjusted odds ratios (aOR) were estimated using conditional logistic regression.</p> <p>Results: The study includes the case group (n=2,666) and the control group (n=10,664). Health disparities were observed among participants. Compared with those who did not have health insurance, those with employer provided insurance (aOR: 0.49, 95%CI: 0.40 – 0.61), Medicare (aOR: 0.62, 95%CI: 0.52 – 0.74), or Medicaid (aOR: 0.80, 95%CI: 0.66 – 0.97) were less likely to develop acidosis. African Americans (aOR: 1.35, 95%CI: 1.15 – 1.58) showed higher acidosis risk. Other major risk factors include liver disease, renal disease, diabetes, and metformin use.</p> <p>Conclusion: Health insurance coverage is a major determinant of acidosis risk. Patients with kidney and liver diseases or diabetes should be monitored carefully for signs of acidosis, especially if they have been prescribed metformin. In future work, for diabetes patients with both kidney and liver diseases, pharmacogenomics analysis will be performed for precision management of metformin-related acidosis risks.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Allison Gatz, Chenxi Xiong, Xiaochun Li, Michael Eadon, Jing Su, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27853Probing Brain Magnetic Susceptibility Alterations in a Mouse Model of Multiple Sclerosis2023-12-13T06:35:10-05:00Adrienne GaughanNian WangSurendra MaharjanAbigail Wallace<p>Multiple sclerosis (MS) is an increasing cause of disability in the United States, characterized by autoimmune demyelinating events in the central nervous system. MS patients can present with a varying range of symptoms and disability due to the chronic inflammatory and relapsing events associated with the disease, such as impaired mobility, slowed cognitive processing, and high probability of disease progression.</p> <p>MS can be morphologically characterized by the damage to the myelin sheath that surrounds axons, oligodendrocytes that produce myelin, and axons that transmit information to different neurons. Due to the complicated mechanism of MS, the advanced MRI methods which can provide both sensitive and specific assessment of MS tissue injury hold the promise to provide critical mechanistic guidance of MS and serve as robust imaging biomarkers for MS. Several animal models have been established to understand the distinct aspects of the disease. Cuprizone, a copper chelator, creates demyelination events comparable to MS, allowing the mouse model to be a representation QSM’s ability to accurately distinguish between and predict acute and chronic demyelination events. Recently, we have demonstrated that the novel quantitative susceptibility mapping (QSM) can identify between the demyelination and<br>remyelination process in the corpus callosum of mice treated with cuprizone. However, how early QSM can detect brain alterations has not been investigated.</p> <p>We acquired high-resolution in vivo whole-brain QSM, T-2 weighted, and magnetization transfer ratio (MTR) images at 0, 2, and 4 weeks after cuprizone administration. The corpus callosum exhibited significant changes in T2-weighted and MTR images at 4 weeks after cuprizone administration. In contrast, QSM decreased significantly in QSM at 2 weeks after cuprizone administration. Since dramatic demyelination only starts after oligodendrocytes depletion (3 weeks after cuprizone treatment), QSM may be able to detect the alteration of oligodendrocytes and serve as a sensitive biomarker even before demyelination occurs.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Adrienne Gaughan, Nian Wang, PhD, Surendra Maharjan, Abigail Wallace, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27854Neuromuscular dysfunction precedes muscle atrophy in C26 tumor-bearing mice2023-12-13T06:51:44-05:00Davis GiffinMorgan ClouseJoshua R. Huot<p>Background: Cancer patients frequently develop skeletal muscle wasting and weakness, which are hallmarks of cachexia, a wasting disease which worsens quality of life and is directly responsible for up to 30% of all cancer-related deaths. While advancements in detection and treatment have increased the population of cancer survivors, skeletal muscle dysfunction can persist for years following cancer remission. We previously demonstrated that late-stage cachexia is associated with impaired skeletal muscle innervation, linking loss of motor unit (MU) connectivity to cancer-induced wasting and weakness. In the present study, we investigated the onset of neuromuscular dysfunction in a preclinical model of cancer cachexia.</p> <p>Methods: CD2F1 male mice (8-week-old) were subcutaneously injected with C26 colorectal cancer cells (1.0x106) or saline and randomized into one the following timepoint groups: day 6, day 8, or day 10 (n=8-10). Animals were assessed for indices of MU connectivity and muscle function at each timepoint. Following functional assessment, skeletal muscles were harvested, weighed, and processed for molecular analyses.</p> <p>Results: 6 days post tumor injection, C26 hosts displayed reductions in neuromuscular junction (NMJ) transmission and motor unit connectivity, while muscle torque and mass were preserved. Specific torque was reduced in C26 hosts at day 8, while reductions in muscle mass or cross-sectional area did not occur until day 10. Molecular analysis revealed alterations of NMJ components as early as day 6 in C26 hosts, further suggesting that neuromuscular dysfunction precedes muscle atrophy.</p> <p>Conclusions: Altogether our data demonstrate that cancer-induced neuromuscular dysfunction precedes cancer-induced muscle atrophy, identifying impaired innervation as an early prognosticator of cachexia progression. Our work supports strategies to counteract impaired neuromuscular function in the treatment of cancer cachexia, in hopes of sustaining quality of life in cancer patients and the growing population of cancer survivors.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Davis Giffin, Morgan Clouse, Joshua R. Huot, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27855Percutaneous Liver Biopsy Adverse Events in Stable Fontan Patients2023-12-13T07:04:29-05:00Brendon GlassSean PfaffChristopher Sinsabaugh<p>Background:<br>In patients who have undergone a Fontan operation, altered cardiac circulation can lead to several organ pathologies, including Fontan-associated liver disease. Transjugular liver biopsies are the standard for assessing liver disease in these patients, however data for a percutaneous approach in these patients is limited. Percutaneous liver biopsies are the preferred method in the general population. The objective of this study was to compare the rate of adverse events for percutaneous liver biopsies in Fontan patients to the general pediatric population.</p> <p>Methods:<br>A retrospective chart review was conducted on percutaneous liver biopsy patients over a five-year period. For each patient, a 90-day period post-biopsy was investigated to look for any indications of adverse events (pain, hemorrhage) and related work-up (imaging, hospital admission), scoring the severity of these events based on SIR adverse event classification. Patients were stratified based on if they underwent a cardiac catheterization procedure immediately prior to biopsy or not.</p> <p>Results:<br>A total of 412 biopsies were reviewed, 367 without cardiac catheterization and 45 with catheterization. Across the entire population, 38 adverse events were found, giving an overall adverse event rate of 9.2%. Comparing populations, non-catheterized patients were found to have an adverse event rate of 9.0%, with a minor rate of 7.2% and a major rate of 1.8%. The catheterized group had an adverse event rate of 11.1%, with a minor rate of 8.8% and a major rate of 2.3%. There were no lethal events. These rates align with reported literature.</p> <p>Conclusion and Potential Impact:<br>There was no significant difference in adverse event rates between Fontan patients and the general population after a percutaneous liver biopsy. This information can guide clinical decisions, as these biopsies are cheaper, less invasive, and do not expose patients to ionizing radiation.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Brendon Glass, Sean Pfaff, MD, Christopher Sinsabaugh, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27856Racial Disparities in Childhood Vaccination Rates2023-12-13T07:20:43-05:00Neal HayhurstMeagan O’Neill<p>Background: Despite the high efficacy and safety of routine vaccinations, most of the United States is currently falling well short of the Healthy People 2020 goals for childhood vaccination rates. A large racial disparity exists within the IU Health (IUH) system, with about a 26% difference between Black/African American (BAA) and white patient vaccination rates as of 2022. Within IUH, the most commonly missed appointment is the 4-month well child check, a critical appointment for staying up to date on vaccinations. In response to this disparity, a pilot program was launched to assist BAA patients in scheduling, attending visits, and getting vaccinated. This study also investigates the roles of insurance, race, ethnicity, and gender in racial disparities of routine vaccination rates among IU Health pediatric patients at the Riley Pediatric Care Center (PCC).</p> <p>Project Methods: A cohort of patients at the PCC clinic who were not meeting vaccination recommendations were compared to the PCC patient population as a whole to identify drivers of under-vaccination. These patients were also compared to patients within the pilot vaccination program to assess program efficacy in scheduling and attending 4-month well child checks.</p> <p>Results: The largest differences between the cohort not meeting the vaccination measure and the PCC patient population were race and insurance status. Patients not meeting vaccination recommendations were more likely to be BAA and to use Medicaid. The pilot program patient population had much higher rates of attendance at 4-month well child checks and vaccination rates for rotavirus among BAA patients than the IUH BAA patient population as a whole.</p> <p>Conclusions: The data from this study will help identify drivers of racial disparities in vaccination rates and guide data-driven and community-informed interventions to ameliorate the disparity. The pilot program has shown great success and warrants strong consideration for increased investment and expansion.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Neal Hayhurst, Meagan O’Neill, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27857Comparing Complication Rates of Transcatheter Aortic Valve Replacement to Surgical Aortic Valve Replacement2023-12-13T07:25:16-05:00Jacob HedbergJames Butler<p>Background/Objective: Transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) are the two procedures used to treat severe symptomatic aortic stenosis. One of the most feared outcomes of both procedures is stroke. Conduction abnormalities and arrhythmias after TAVR are relatively common, but few studies have been done comparing the rate of these events between TAVR and SAVR. The objective of our study is to find if there are any differences between the rates of stroke, conduction abnormalities, and arrhythmias between patients that have undergone TAVR and patients that have undergone SAVR.</p> <p>Methods: The CRC/Sidus Real World Evidence Cardiology Dataset was used to obtain samples for this project. Patients who underwent TAVR and SAVR were identified using CPT codes. These two cohorts of patients were tracked for complications between 0 to 30 days after the procedure and between 0 days to 1 year after the procedure using ICD-10 codes.</p> <p>Results: Patients who underwent TAVR (n=3621) were much more likely to have conduction disorders and arrhythmias both in the 0-30 day range and 0 days-1 year range after the procedure compared to patients who underwent SAVR (n=2137). Cerebral infarction and transient cerebral ischemic attack rates were also higher in the TAVR group. Mortality rates for TAVR were lower than mortality rates for SAVR, both 30 days and 1 year after the procedure.</p> <p>Conclusion/Impact: TAVR has revolutionized aortic valve replacement and allowed many patients with aortic stenosis (many of whom are at high surgical risk) a minimally invasive option to improve their quality of life. Finding ways to reduce the rates of stroke, arrhythmias, and conduction abnormalities; for example, through improved devices and techniques, and improved<br />anti-thrombotic therapy, is extremely important as TAVR becomes more and more widely utilized.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Jacob Hedberg, James Butler, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27858Comparison of Wound Outcomes for Absorbable versus Non-absorbable Suture after Carpal Tunnel Release2023-12-13T07:41:39-05:00Cameron HarmonJeffrey N. GrossJoshua M. AdkinsonBrian Christie<p>Background and Hypothesis:<br>Carpal tunnel release (CTR) is a common hand surgery procedure. Despite the large volume of CTRs performed worldwide (400,000-600,000 cases/year), there is no consensus as to the optimal suture material for incision closure. In this study, we sought to compare outcomes of absorbable and non-absorbable suture for skin closure after CTR. Our hypothesis was that that there is no statistically or clinically significant difference in wound-related outcomes between the cohorts.</p> <p>Project Methods:<br>All patients who underwent primary open carpal tunnel release (CTR) at a large, public county hospital in Indianapolis, IN were identified by CPT code (64721). All patients were treated by one of two fellowship-trained hand surgeons. The most recent 50 patients treated between September 2022 and May 2023 by each surgeon were identified. Surgeon “A” uses 4-0 vicryl rapide for closures (absorbable). Surgeon “B” uses 4-0 nylon for closures (non-absorbable). Adverse events (AE) were defined as infection, dehiscence, or suture granuloma observed at any follow-up appointment. This study was approved by the Institutional Review Board.</p> <p>Results:<br>100 patients were identified - 4 patients were lost to follow-up and were excluded from the study. Of the remaining 96 patients, 46 received absorbable suture and 50 non-absorbable suture. Of the 46 patients who received absorbable suture, 8 experienced AE (17.4%). None of the 50 patients who received non-absorbable suture experienced an AE. There was a statistically significant difference in AE between the absorbable and non-absorbable suture cohorts (<em>p</em>=0.002). Patients with absorbable suture averaged 1.61 follow-up appointments, whereas those with non-absorbable suture averaged 2.32 (<em>p</em>=.0008).</p> <p>Conclusion and Potential Impact:<br>In this study, absorbable suture resulted in more wound-related complications after CTR. However, patients with non-absorbable suture had more post-operative follow-up appointments. These findings should be considered when selecting suture material for skin closure after CTR.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Cameron Harmon, Jeffrey N. Gross, MD, Joshua M. Adkinson, MD, Brian Christie, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27859Analysis of the Binding Partners of Clusterin in their Role in Increased Intraocular Pressure in Glaucoma2023-12-13T07:49:30-05:00Clay HeppAnoop MageshAvinash SoundararajanPadmanabhan Pattabiraman<p>Background and Objective:<br>Elevated intraocular pressure (IOP) is a risk factor for primary open-angle glaucoma (POAG). Clusterin (CLU) is a secretory chaperone protein found in trabecular meshwork tissue that is implicated with POAG risk. In this study, we aimed at understanding the role of CLU and its binding partners in IOP homeostasis and POAG pathology.</p> <p>Methods:<br>Normal trabecular meshwork (NTM) cell lines were used. Half of the NTM cell lines were transfected with adenovirus empty (AdMT) while the other half of the NTM cell lines were transfected with adenovirus clusterin with histidine tag (AdCLUHIS). AdCLUHIS allows for the overexpression of CLU HIS in the NTM cells. After 72 hours of transfection, the media and cell lysate were collected. As CLU is a secretory chaperone protein, the media was analyzed. Immunoprecipitation (IP) was conducted to isolate CLU HIS and all the proteins bound to it. Western blot analysis was conducted to confirmed IP worked successfully. Once it was confirmed that CLU HIS with all its binding partners was isolated successfully using IP, the media samples were sent to proteomics to determine all the specific proteins that are bound directly to CLU.</p> <p>Results:<br>Western blot analysis confirmed that the overexpression of CLU HIS was successfully accomplished through adenovirus transfection. In addition, Western blot analysis confirmed that IP worked successfully. At the current moment, results of proteomics are still being developed, so the specific binding partners of CLU are still unknown at the time.</p> <p>Conclusions and Potential Impact:<br>Our preliminary study suggests that CLU can be overexpressed via adenovirus and analyzed via IP. Understanding this allows for the purification of the protein and its attached binding partners. Identifying these binding partners can be novel targets for improving aqueous humor outflow through trabecular meshwork to decrease IOP and decrease one’s risk for POAG.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Clay Hepp, Anoop Magesh, Avinash Soundararajan, Padmanabhan Pattabiram, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27860Peanut-Specific Immune Response in Bcl6 Heterozygote Knockout Mice2023-12-13T08:01:53-05:00Riley HoganAbdullahi AbdiAlexander Dent<p>Food allergies are common in the United States, yet the mechanisms for the development and regulation of IgE, one of the most important antibodies for these allergic responses, are not fully understood. Two cells, T follicular helper (TFH) and T follicular regulatory cells (TFR) have been shown to be critical in the production IgE in particular, as when these cells are absent, IgE<br>production is significantly decreased while IgG1 production remains around normal levels. However, it has not been determined whether haploinsufficiency for Bcl6 or the number of TFH and TFR cells that develop in our mouse food allergy model affect allergic IgE responses. In this project, we show that haploinsufficiency of Bcl6 unexpectedly leads to a trend toward an increase in the number of TFH and TFR cells within mesenteric lymph nodes with trend toward an increase in IgE and IgG1 in CD4-Cre-Bcl6-fl/+ mice compared to wildtype mice. However, haploinsufficiency for Bcl6 led to a loss of TFH and TFR cells in the spleen. This points to the possibility that TFH and TFR production, along with antibody production, is regulated differently in the gut compared to the rest of the body. Much remains to be understood about how TFH and TFR cells regulate allergic IgE responses.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Riley Hogan, Abdullahi Abdi, Alexander Dent, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27861Clinical Uses of Nanopore Sequencing in Recurrent Acute and Chronic Otitis Media2023-12-13T08:09:47-05:00Ben HoltzlanderSarah BurginGrace PerkinsGuang-Sheng LeiThomas Davis<p><em>Background</em>. Otitis Media (OM) is a widespread problem that has an incidence of 10.85% worldwide, 51% occurring under the age of 5. Emergence of drug resistant bacteria contribute to high incidence of recurrent acute otitis media (AOM) and chronic otitis media with effusion (COME). Despite this, the standard of care for treatment is empiric antibiotics. Molecular microbiology diagnostics may enable clinicians to provided pathogen directed antibiosis. Nanopore sequencing is a highly accurate method of identifying a broad range of pathogens when compared with multiplex PCR. We hypothesize that nanopore sequencing is an effective method for detection of pathogens in the middle ear and nasopharynx of patients with recurrent or chronic OM.</p> <p><em>Methods</em>. Bacterial Culture, multiplex PCR (BioFire PNA panel), and nanopore sequencing (MinIon, Oxford Nanopore Technologies) were tested on 60 middle ear and nasopharynx samples. Chi-Square test was used to examined differences in bacterial identification among the methods.</p> <p><em>Results</em>. Bacterial identification using nanopore proves to be more sensitive in identification of 16 of the 18 unique pathogens when compared with multiplex testing. Of the 5 most common OM bacterial pathogens (<em>S. pneumoniae, M. catarrhalis, H. influenza, S. aureus, P. aeruginosa</em>), nanopore identified 3 pathogens (S. pneumoniae, M. catarrhalis, P. aeruginosa) at higher levels, 1 at the same rate (<em>H. influenza</em>), and 1 did not receive any readings (<em>S. aureus</em>).</p> <p><em>Conclusion</em>. This is the first study to utilize nanopore sequencing to assess pathogens in the middle ear fluid of children with OM. While nanopore genomic sequencing is still in the early stages of use, it has potential to comprehensively identify bacteria with more sensitivity when compared to the current clinical standards. The next step of data analyzation will include bacterial identification in nanopore that multiplex PCR and traditional bacterial cultures cannot test for.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Ben Holtzlander, Sarah Burgin, MD, Grace Perkins, Guang-Sheng Lei, Thomas Davis, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27862Effect of Oxygen Tension on Glioblastoma Cell Growth2023-12-13T08:19:23-05:00Luke JacksonJack MullerElise O’HerronScott CooperAngela Richardson<p>Background and Hypothesis:<br>Glioblastoma (GBM) is an aggressive primary malignancy of the CNS with a dismal prognosis (~15-20 months) despite standard of care therapies. The poor prognosis of GBM despite ongoing research may be due to inaccuracies in preclinical models of the disease. Cell lines typically used to study GBM are exposed to ambient air containing 21% oxygen (normoxia compared to physiologic oxygen tension, physoxia, ~5%). In extracranial tumors, exposure to the oxygen in ambient air triggers epigenetic changes that alter cell growth, metabolism, and treatment responsiveness. The aim of this study is to obtain preliminary data on the impact of<br>physiologic oxygen tensions on primary glioma cell growth in vitro.</p> <p>Experimental Design:<br>Growth of primary glioma cell lines (GB43, GB10, GB001) and one immortalized cell line (293T HEK) was assessed in normoxia and physoxia. All cell lines were plated at 10,000 cells per well. Cells were harvested and counted in triplicate on days 2, 4, 6, 8, 10, 12. On each day the cells were counted, the media in the remaining wells was changed. This experiment was repeated three times. Wound healing assays with all cell lines were also performed at normoxia and physoxia.</p> <p>Results:<br>Cells line growth curves were plotted and showed consistent exponential growth after counting on day two. From these graphs, the cell doubling time was calculated over a period of four days during which the cells were undergoing exponential growth.</p> <p>Conclusions:<br>Current results indicated that primary glioblastoma cell lines grow at different rates at differing oxygen tensions. In ongoing studies, we are exploring the effect of low oxygen tensions on functional assays such as wound-healing. Future work will assess rates of growth and functional consequence of physoxia in tumor samples never exposed to ambient air to most accurately recapitulate the in-situ environment.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Luke Jackson, Jack Muller, Elise O’Herron, Scott Cooper, Angela Richardson, MD, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27863Comparison of Sinus Flora Using Various Next-Generation Sequencing Techniques Versus Standard Culturing2023-12-13T08:35:05-05:00Benjamin KistlerManav PatelThomas DavisGuang-Sheng LeiDanielle SchreiberVijay Ramakrishnan<p>Background:<br>Next generation sequencing methods are being developed to help diagnose infectious diseases at the point of care and to help resolve discrepant results. These new methods hope to replace longer, more tedious sequencing methods such as Sanger/shotgun sequencing and less sensitive culture results to provide a clinical diagnosis and start appropriate treatment sooner. In lieu of dated techniques, with next generation sequencing the physician could analyze samples in their clinic with relative ease and receive a sensitive diagnosis in a fraction of the time.</p> <p>Objective:<br>To compare percent agreement between standard culturing results of swabbed sinus samples on blood and chocolate agar to BIOFIRE® FILMARRAY® results, and use Oxford Nanopore and 16s illumina sequencing results to resolve discrepancies.</p> <p>Study design:<br>Swabs were taken of the nasal sinuses of 21 patients and flash frozen. Some of these swabs (15/21) were sequenced with 16s illumina sequencing. All these swabs were put into a saline solution and plated on blood and chocolate agar plates as a 1:100 loop dipped into the solution and as the original swab. These solutions were sequenced through the BIOFIRE® FILMARRAY® Torch System on a pneumonia and blood culture (BCID2) panel and through the Oxford Nanopore® MinION Mk1C® system.</p> <p>Results:<br>The pneumonia panel had 36% agreement with blood agar and 52% agreement with chocolate agar plates. Using the top 3 genus results, either Nanopore or 16s illumina sequencing resolved 92% of discrepancies between the pneumonia panel and blood agar and 90% of discrepancies between the pneumonia panel and chocolate agar plates. The blood culture panel had 43% agreement with blood agar and 57% agreement with chocolate agar plates. Nanopore or 16s illumina sequencing resolved 92% of discrepancies between the blood panel and blood agar and 89% of discrepancies between the blood panel and chocolate agar.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Benjamin Kistler, Manav Patel, Thomas Davis, PhD, Guang-Sheng Lei, Danielle Schreiber, Vijay Ramakrishnan, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27864Development of Assistive Devices for Eye Drop Administration in Patients with Cerebral Palsy2023-12-13T08:46:27-05:00Anthony KluemperKristi HapeArthur L. Chlebowski<p>Background:<br>Cerebral Palsy is a non-progressive neurological disorder that affects movement, posture, and muscle coordination, caused by damage to the developing brain. It is one of the most common motor disabilities in childhood, with significant implications for an individual's physical and functional abilities. The severe impact on fine motor control in Cerebral Palsy patients is often most evident when performing actions where precision and accuracy are needed such as applying eye drops. This work addresses the design, development, and deployment of assistive devices for fine motor control of objects.</p> <p>Methods:<br>Using 3D modeling and printing, three prototypes were created and assessed for their efficacy in assisting patients with eye drop administration based on the needs and abilities of the individual, considering factors such as ease of use, affordability, and adaptability to different environments. After evaluation, changes were made to each prototype in order to better adapt the design according to the feedback received.</p> <p>Results:<br>Three final products were presented for patient review. Two of these addressed deficiencies of eye drop accuracy and the other fine motor control and bottle manipulation. Patients noted in their final evaluation of the assistive devices improvement in ability to manipulate eye drop bottles as well as better ability to aim the eye dropper for application in comparison to previous methods of application.</p> <p>Conclusion and Impact:<br>By understanding the challenges faced by the individual and evaluating the need for assistive devices, the fine motor challenges associated with eye drop administration due to cerebral palsy were addressed and three valuable products were created that improved patient autonomy and quality of life. Additionally, these devices could be useful for patients with a variety of motor limitations, enabling self-sufficiency while improving ease and accuracy of administration and minimizing waste.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Anthony Kluemper, Kristi Hape, Arthur L. Chlebowski, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27865Blood Product Utilization Among Adolescent and Young Adult Patients with Acute Lymphoblastic Leukemia: A Single Center Ex2023-12-13T08:53:50-05:00Jacquelyn KnobelsdorfSandra K. AlthouseSandeep Batra<p>Background: Adolescent and young adult (AYA, 15-39 years old) patients with acute lymphoblastic leukemia (ALL) often experience pancytopenia and severe immunosuppression. Particularly during intensive phases of chemotherapy, allogeneic blood transfusion support is essential in their care. The utilization of both red blood cell (RBC) and platelet transfusions, as well as the thresholds used to determine when transfusions are needed, are poorly described in this population. The objective of this study is to describe blood product utilization in AYA patients with ALL treated at our institution.</p> <p>Methods: A cohort of 20 AYA patients with ALL treated at Riley Hospital for Children from October 2020 to July 2023 were identified for data collection. Pre- and post-transfusion laboratory values, transfusion totals, comorbid events or complications, transfusion reactions, and minimal residual disease (MRD) values were collected and analyzed. All values reported are mean ± standard deviation for continuous variables and n (%) for categorical variables. Values were calculated individually for each patient for each phase of therapy and averaged across all patients.</p> <p>Results: Patients studied had varying needs for transfusions throughout their therapy (50.75 ± 48.06), with an average of 22.95 ± 15.65 RBC transfusions and 25.60 ± 29.65 platelet transfusions. Patients being treated with standard chemotherapy protocols required more<br>transfusions during induction (14.13 ± 21.56) and delayed intensification (14.07 ± 24.29) phases compared to other phases. Patients with MRD positive status required more transfusions (69.14 ± 58.14) than patients with MRD negative status (40.92 ± 40.84).</p> <p>Conclusions and Potential Impacts: This study helped to elucidate the need for transfusions among the AYA ALL patient population, throughout the different phases of treatment. These findings hold implications for establishing guidelines that could clarify when transfusions should be given in this population, helping physicians provide the best care to future patients.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Jacquelyn Knobelsdorf, Sandra K. Althouse, Sandeep Batra, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27866Group Prenatal Care Models, Experiences, and Outcomes: An Integrative R2023-12-13T09:24:54-05:00Michelle LaTurnerBaraka Muvuka<p>Background:<br>The United States (US) has the highest maternal and infant mortality rates among developed countries. Indiana has the third highest maternal mortality rate in the US. Group Prenatal Care (GPC) was piloted in the early 1990s to improve perinatal experiences and outcomes through enhanced social support and education. Further research is needed as GPC is increasingly implemented in diverse contexts. This study critically synthesized current evidence on GPC models, experiences, and perinatal outcomes in the US to inform a Community Based Participatory Research Partnership between Indiana University School of Medicine-Northwest and Community HealthNet.</p> <p>Methods:<br>This integrative review utilized PRISMA guidelines to conduct a systematic search in Embase, CINAHL, and PubMed. Two researchers screened articles for inclusion criteria and quality. Studies were included if they were empirical research or meta-analyses conducted in the US and published in English between January 2013 and June 2023. Data synthesis utilized a qualitative analytical approach that sorted findings thematically.</p> <p>Results:<br>We retained 98 articles, including 8 meta-analyses, 4 randomized trials, 3 cluster randomized trials, 3 quasi-experimental studies, 4 prospective cohort studies, 12 observational studies, 19 qualitative studies, and 46 retrospective cohort studies. There were several GPC models adapted to high-risk groups such as persons living with HIV, gestational diabetes, pre-existing or pregnancy-induced hypertension, and substance use disorders. GPC was associated with decreased preterm births among low-income and minority women, with more significant reductions when attending 5 or more GPC sessions. GPC improved psychosocial outcomes including satisfaction with care, empowerment, and social connectedness. It was also associated with increased breastfeeding rates in adolescents and African Americans, and increased contraception use among adolescents.</p> <p>Conclusions:<br>Engaging in GPC may have benefits for high-risk pregnancies, adolescents, low-income, and minority populations. More studies are needed to evaluate GPC’s impacts on perinatal experiences and outcomes among high-risk women.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Michelle LaTurner, Baraka Muvuka, PhD, MPHhttps://journals.iupui.edu/index.php/IMPRS/article/view/27867Long-Term Outcomes in Stage II/III Thymic Epithelial Tumor Patients Treated with Post- Operative Radiotherapy2023-12-13T09:29:54-05:00Nikhitha LavuAneesha AnandPatrick J. LoehrerKenneth A. Kesler<p>Thymic epithelial tumors (TETs) are rare malignancies that originate in the anterior mediastinum. Unlike other tumors of the chest, TETs recur most often in the pleura. The primary treatment of early stage TETs is surgical resection, with the role of adjuvant chemotherapy/radiotherapy controversial. Mixed results have been reported as to whether postoperative radiotherapy (PORT) decreases tumor recurrence or time to recurrence, but PORT can cause short-term and long-term toxicity. Therefore, assessing the benefit of PORT is important. For the present retrospective study, we created a database of stage II/III TET patients seen at Simon Cancer Center from 2000-2023 to examine long-term outcomes. Of the 214 stage II/III TET patients that underwent surgery in the database, 67 patients treated with PORT were isolated. Subsequently, 67 patients who did not receive PORT were matched to the PORT population based on similarities in histology, surgical margins, and chemotherapy received. Local vs. distant tumor recurrence, long-term complications, and overall survival were then compared. The PORT population had the following histologic distribution: 3 Type A, 3 Type AB, 47 Type B1/B2/B3, and 14 carcinoma; for the non-PORT population: 8 Type A, 13 Type AB, 36 Type B1/B2/B3, and 10 carcinoma. There were 16 stage IIA, 6 stage IIB, and 45 stage III patients in the PORT population, and 17 stage IIA, 9 stage IIB, and 41 stage III patients in the non-PORT population. The PORT population had 57 recurrences, whereas the non-PORT population had 20 recurrences (p=1.02 x 10<sup>-9</sup>). The PORT population had 5 deaths and 50 instances of long-term complications, while the non-PORT population had 3 deaths and 25 instances of long-term complications. Overall, these data do not support the routine usage of PORT in resected Stage II/III TET. Further analysis in larger data sets are warranted.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Nikhitha Lavu, Aneesha Anand, Patrick J. Loehrer, MD, Kenneth A. Keslerhttps://journals.iupui.edu/index.php/IMPRS/article/view/27868Blood Culture Contaminations: Interventions and Culture Characteristics2023-12-13T09:38:02-05:00Aimee LeeVanessa SchwietermanChristine Motzkus<p>Background/Objective:<br>Blood cultures are collected in patients with serious illnesses who are at risk of bacteremia. However, some blood cultures are contaminated which may lead to adverse health outcomes for patients such as an increased length of stay and the unnecessary utilization of antibiotics. The emergency department (ED) has been found to be a frequent source of blood culture contamination. We aimed to identify characteristics and consequences of blood culture contamination at IUH Bloomington.</p> <p>Methods:<br>Chart review of blood cultures collected at IUH Bloomington in January 2023 was utilized to extract variables including intravenous location and hospital location of blood draw, number and identification of antibiotics given, length of stay, and organisms identified in the blood cultures. Data were securely maintained in REDCap.</p> <p>Results:<br>The median length of stay for individuals with contaminated cultures in January was found to be 4 days which was comparable to individuals with negative cultures. Most commonly, contamination occurred from the ED with it being responsible for 33/34 contaminated cultures. The most frequently utilized antibiotic across all groups was vancomycin – with both the positive and contaminated groups having a greater percentage of individuals receiving a course of the antibiotic with a mean course of 3.43 days. The most common contaminant was found to be coagulase negative <em>Staphylococcus</em>.</p> <p>Conclusion and Implications:<br>Lower rates of blood culture contamination may contribute to lower length of stay and improved antibiotic de-escalation strategy. Identification of culture characteristics may guide future endeavors in infection control policies.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Aimee Lee, Vanessa Schwieterman, Christine Motzkus, MD, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27869The Relationship Between Intensive Care Unit (ICU) Delirium Severity and 2-Year Mortality2023-12-13T09:43:55-05:00Rachel LehmanSamreen JawaidHeidi LindrothJared MeekerAnthony J. PerkinsSophia WangSujuan GaoSikandar H. KhanBabar A. Khan<p>Background:<br>Delirium is an acute brain dysfunction characterized by altered cognition, attention, and level of consciousness. The presence of delirium is associated with increased risk of mortality, neurocognitive decline, and physical impairment; however, the role of ICU delirium severity in long-term health outcomes is less understood.</p> <p>Objective:<br>Characterize the relationship between delirium severity and mortality risk in ICU survivors 2-years after discharge.</p> <p>Methods:<br>A secondary analysis was performed on patient data collected in two randomized controlled trials (Pharmacological Management of Delirium and Deprescribing in the Pharmacologic Management of Delirium, 2009-2015). Participants received delirium assessments twice daily during hospitalization via the Confusion Assessment Method for the ICU (CAM-ICU-7). Patients enrolled at Eskenazi Hospital with complete mortality data were included in this study. Mean delirium severity was categorized as rapidly resolving (0-2), mild to moderate (2.1-5), or severe (>5). Cox proportional hazard model was used to quantify mortality risk associated with delirium severity. Analyses were adjusted for patient demographics, comorbidities, and severity-of-disease.</p> <p>Results:<br>The cohort (n=434) was 54.6% female and 48.6% African American with an average age of 59.8 (SD 16.4). The admission diagnosis was acute respiratory failure/sepsis in 47.9% of patients across medical (n=272), progressive (n=52), and surgical (n=110) ICU types. Approximately one third of the original cohort (n=143) died within 2 years of index discharge. In the multivariate analysis, patients with severe delirium (>5) had nearly twice the adjusted hazard ratio for 2-year mortality compared to patients with mild-moderate delirium (aHR 2.1 [95% CI, 1.3-3.4] and aHR 1.1 [95% CI, 0.7-1.6], p=0.008).</p> <p>Conclusion:<br>Severe delirium during ICU stay was significantly associated with increased 2-year mortality risk in comparison to mild-moderate (subsyndromal) delirium.</p> <p>Impact:<br>The relationship between delirium severity and 2-year mortality underscores the need for further research on the mechanisms underlying ICU delirium and specific interventions to improve long-term outcomes.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Rachel Lehman, Samreen Jawaid, Heidi Lindroth, Jared Meeker, Anthony J. Perkins, Sophia Wang, Sujuan Gao, Sikandar H. Khan, MS, DO, Babar A. Khan, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27871Tobacco smoking and early onset cataracts2023-12-13T09:58:46-05:00Albab UddinDavid Gross<p>Background and Hypothesis:<br>Cataracts are among the leading causes of blindness in the world. Smoking tobacco has been linked to cataract formation in old age. However, its linkage in causing an earlier onset is much more questionable. Assessing this linkage can help identify risk factors and help understand the causes and pathogenesis in development of cataracts over time. This can help direct modifiable risk factors in patients to prevent early deterioration in health, finance, physical capabilities, and overall comfort. It is hypothesized that history and intensity of smoking tobacco correlates with earlier onset cataracts.</p> <p>Experimental Design or Project Methods:<br>Patient data of patients aged 40-65 were gathered from the last two years of cataract surgeries from Deen-Gross Eye Centers EMR (n=718). Age at date of surgery was used as observed value for determining earlier onset, and pre-operation charts were used to collect patient data on smoking status (light, someday, every day, heavy, former, never), age, gender, hypertension, diabetes, number of eyes operated on, family history (cataracts/glaucoma), and glaucoma. Statistical analysis was performed among the gathered data.</p> <p>Results:<br>Statistical analysis revealed no significant difference in the ages of cataract surgeries between smokers and non-smokers. Controlling for non-hypertensive and non-diabetic patients revealed a similar result. There was no significant difference in smoking status between ages 40-55 and ages 56-65 who underwent surgery. There was no significant difference in age of surgery among each of the individual types of smokers.</p> <p>Conclusion:<br>No significant associations were found. This calls for further research to better understand the linkage between tobacco smoking and cataracts, as well as the pathogenesis of earlier onset cataracts. No modifications in directing patient care can be made yet.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Albab Uddin, David Gross, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27873Kidney Disease Awareness and Knowledge Among Families and Pediatric Survivors of Severe Acute Kidney In2023-12-13T10:03:09-05:00Julia VanderkolkMichelle C. Starr<p>Background: Acute kidney injury (AKI) is common in pediatric patients and is associated with poor outcomes including increased risk of chronic kidney disease. It is unknown whether pediatric AKI survivors and their families are aware of their AKI diagnosis and understand the associated risks. We are seeking to identify awareness and disease-specific knowledge among pediatric AKI survivors and their families.</p> <p>Objectives: We hypothesize that pediatric AKI survivors and their families have a low awareness of their diagnosis and want more information about kidney health.</p> <p>Design/Methods: We performed a cross-sectional survey of AKI awareness and knowledge in pediatric patients with KDIGO Stage II or III AKI and their families near the time of discharge from Riley Hospital for Children. Families answered questions on AKI diagnosis awareness and AKI knowledge using the Kidney Knowledge Survey (KiKS).</p> <p>Results: Of 16 families included in this analysis, 75% were unaware they had experienced AKI and 94% were unaware they had a ‘problem with their kidneys’. Overall, the median AKI objective knowledge score was 60% (IQR: 31%, 69%). There was no difference in knowledge score between those that recognized their episode of AKI and those that did not. In total, 69% of families correctly defined AKI as when ‘your kidneys suddenly stop working well’. Most families recognized dehydration (56%) and infection (81%) as risk factors for AKI, however fewer recognized other risk factors such as ibuprofen use (31%). Only 38% of families reported that someone had discussed AKI during their admission, and 88% stated they wanted to learn more about AKI.</p> <p>Conclusion: Most families of pediatric survivors of severe AKI were unaware that their child had AKI or problems with their kidneys. Many lacked understanding of AKI risk factors and knowledge of kidney health and desired more information.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Julia Vanderkolk, Michelle C. Starr, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27874A Molecular Dynamics Investigation of Ligand-Mediated PPARγ Transrepression2023-12-13T10:07:57-05:00Lauren WardRaymond KongerSachiko KoyamaJonah Z. Vilseck<p>Background and Hypothesis: PPARγ is a nuclear receptor expressed in most cells of the body and exerts metabolic function, including adipocyte differentiation and insulin sensitization. This mechanism is termed transactivation, where ligand binding leads to transcription of target genes. However, PPARγ also has a transrepression activity, where ligand binding inhibits other transcriptional pathways, leading to regulation of the immune system. While the molecular mechanisms of transactivation are well understood, there is little research on the mechanisms of transrepression. Previous studies have implied that these activity states act independently and can be selected for in small molecule design campaigns, but this has yet to be accomplished. Therefore, the aim of this project was to investigate if distinct molecular interactions exist between PPARγ transactivation versus transrepression using a combined computational and structural biology approach.</p> <p>Methods: Molecular dynamics (MD) simulations were performed using the CHARMM molecular modeling software to produce 300 ns simulations of PPARγ-ligand complexes. Simulations were analyzed to identify potential protein-ligand interactions, and distances were measured between atoms of interest and compared.</p> <p>Results: Although PPARγ’s binding site is large, structural analyses showed that most ligands remained near their initial starting position within the binding pocket throughout an MD simulation. Starting coordinates were taken from previously solved crystal structures or via manual docking based on molecular similarities. Four residues were identified to consistently interact with most of the ligands: Arg280, Ser342, Glu259, and Cys285. These residues differ from previously reported interactions associated with PPARγ transactivation.</p> <p>Conclusion: Our results suggest that these residues may play a role in PPARγ transrepression, but these conclusions are preliminary and should be confirmed through further investigation. Future research would include performing replicate simulations and mutational analyses to further explore the involvement of these residues in PPARγ transrepression. Additional PPARγ ligands should also be explored.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Lauren Ward, Raymond Konger, Sachiko Koyama, Jonah Z. Vilseck, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27875Fracture-Induced Effects on the Onset & Progression of Alzheimer’s Disease2023-12-13T10:14:11-05:00Hannah S. WangElizabeth ScottMurad K. NazzalWilliam A. VarnerReginald ParkerTyler J. MargettsAlexander HarrisAshlyn J. MorrisSonali J. KarnikRachel J. BlosserAmy CreecySarah MostardoMarko DragisicJill C. FehrenbacherKathryn D. FischerAlexandru MovilaAdrian L. OblakMelissa A. Kacena<p>Alzheimer’s disease and related dementias (AD/ADRD) are multifactorial, highly heterogeneous, and complex age-dependent disorders that severely affect memory and cognitive function, impacting nearly 35.6 million people worldwide. In the elderly, dementia increases the risk of falls and fractures by 2-3 times, due in part to neurovascular instability, low bone mineral density due to pre-existing osteoporosis, and poor musculature supporting joints due to cachexia and/or sarcopenia.</p> <p>While the occurrence of fractures due to AD/ADRD is well documented, an association between fractures and AD/ADRD onset or progression is underappreciated and warrants additional investigation. We aim to investigate the mechanistic actions underlying fracture healing as a precipitating event for AD/ADRD pathogenesis.</p> <p>Four-month-old, male, 5xFAD (AD model) and wild-type control (C57BL/6) mice were divided into 2 groups: surgically induced femoral fractures and uninjured mice. Prior to surgery mice underwent baseline AD behavior testing including: spontaneous alternation in the y-maze, light-dark exploration in the open field, and active place avoidance assays. Mice are undergoing weekly x-ray imaging to monitor fracture healing progression and longitudinal AD behavior testing. 22 weeks post-surgery mice will be euthanized, and femurs and brains collected. Femurs will undergo uCT imaging and histological assessment of bone healing and immunohistochemical assessment of inflammatory markers. Brains will be processed for histology and neuroinflammatory marker analysis, including Aβ plaque deposition, tau tangles, neuronal survival, neurogenesis, and activation/proliferation of microglia and astrocytes.</p> <p>At the conclusion of the study, we expect to see an increase in neuroinflammatory markers and delayed fracture healing in the experimental 5xFAD group. We anticipate that compared to uninjured controls, femoral fracture results in cognitive decline, Aβ<br>accumulation/neurodegeneration, increases in neuroinflammation, and vascular impairment. We anticipate finding a correlation between fracture and worsened AD outcomes. By uncovering the mechanisms underlying this relationship, we hope to guide future studies to develop more robust therapeutics.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Hannah S. Wang, Elizabeth Scott, Murad K. Nazzal, William A. Varner, Reginald Parker, Tyler J. Margetts, Alexander Harris, Ashlyn J. Morris, Sonali J. Karnik, Rachel J. Blosser, Amy Creecy, Sarah Mostardo, Marko Dragisic, Jill C. Fehrenbacher, Kathryn D. Fischer, Alexandru Movila, Adrian L. Oblak, Melissa A. Kacena, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27877Exploring Community-Based Strategies to Overcome Barriers to Hypertension Education and Management in Underserved Areas2023-12-13T10:35:04-05:00Ugonna AdinduLynn Witty<p>Objective:<br>In the United States, there are over 119.9 million adults who have been diagnosed with hypertension, representing nearly half of the adult population. Of this population with high blood pressure, 75% of Americans’ hypertension remains uncontrolled. Such control rates are significantly lower among individuals of racial and ethnic minorities as compared to their white counterparts, especially those in underserved areas. We hypothesize that the identification of community-based interventions and strategies to combat barriers to hypertension treatment and education could improve management in these populations.</p> <p>Project Methods:<br>In this study, we looked through various peer reviewed articles on community-based care and hypertension rates among minorities, exploring study design and limitations to develop a questionnaire focused on access to hypertension education. This survey was distributed randomly during outreach events around Muncie, Indiana to anyone who wished to participate, non-minority groups included. The questionnaire asked about various hypertension and healthcare barrier identification factors with a final question of whether said participant would benefit from a hypertension education course.</p> <p>Results:<br>The participants’ responses were across the board. Regarding hypertension knowledge, participants were asked about their diagnosis, as well as their level of knowledge of hypertension and its management; participants exhibited varying levels of knowledge. Understanding key aspects of management, including medication adherence, diet, physical activity, and potential complications and warning signs, also varied among participants. Overall, these preliminary survey results highlight the diverse characteristics and experiences of participants related to hypertension, access to healthcare, and hypertension knowledge.</p> <p>Potential Impact:<br>This study could provide information for those looking to establish community-based organizations in underserved areas. Increasing the magnitude of such teams and advocating for more interventions against barriers to hypertension education could increase not only the health of those in such communities, but also the overall wellbeing of all people in the United States.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Ugonna Adindu, Lynn Witty, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27878Mental Health Assessments in Emergency Department Patients: Assessing Longitudinal Follow-up and Retest Reliability (MCAT-2) [Provisional Baseline Analysis]2023-12-13T10:39:59-05:00Andres AlarconNaman SatsangiPaul Musey<p>Background/Objective:<br>The prevalence of anxiety and depression in adults in the United States is high with many experiencing ≥1 episode of anxiety or depression over a given year. Despite this, diagnoses of anxiety and depression in patients presenting to the ED for somatic complaints are seldom, relative to the population prevalence. Current fixed-item anxiety and depression screening tools have variable specificity and sensitivity, but adaptive screening tools such as the Computerized Adaptive Testing-Mental Health tool (CAT-MH) are thought to provide improved diagnostic characteristics and precision over fixed item tools. Our objective is to establish the reliability of<br>its depression and anxiety severity assessments in patients initially screened in an ED setting and reassessed over 30 days.</p> <p>Methods:<br>We are conducting a longitudinal observational study among adult ED patients presenting with somatic, non-mental health complaints. The CAT-MH, Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-8 (PHQ-8), are administered to randomly selected patients meeting enrollment criteria after informed consent. Participants are reassessed at 1-, 2-, and 4 weeks after ED discharge and analyzed for longitudinal test-retest reliability and sensitivity to change in score severity over time.</p> <p>Results:<br>In this ongoing study, we present baseline anxiety and depression severity assessments for the first 49 enrolled patients (Mean age of 37, 73% female, 49% white, 47% black). Fixed item tools (GAD-7 and PHQ-8) categorized 16% and 6% of patients as moderate and severe anxiety respectively vs 19% and 15% as moderate, and moderately-severe/severe depression. In comparison, CAT-MH categorized 8% and 10% as moderate and severe anxiety.10% and 6% were categorized as moderate and severe depression.</p> <p>Conclusion:<br>In this longitudinal observational study, we present baseline data for the first 49 out of 100 planned patients. Upon completion of the study, we hope to find that the severity assessments from CAT-MH remain stable over 30 days.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Andres Alarcon, Naman Satsangi, Paul Musey, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27880Assessing the Severity of Portal Hypertension: Is Liver or Spleen Stiffness Measurement an Alternative to the Gold Standard, Hepatic Vein or Porto-Systemic Pressure Gradient?2023-12-13T10:46:26-05:00Yasmin A. AliPaul M. HasteRaj Vuppalanchi<p>Introduction: Liver stiffness measurement (LSM) and spleen stiffness measurement (SSM) are increased in patients with cirrhosis and portal hypertension (PH). However, increased SSM values are associated with presence of esophageal varices. Currently, the gold standard for risk stratification in patients with compensated advanced chronic liver disease (cACLD) is by measurement of portal pressure through assessment of hepatic vein or porto-systemic pressure gradient (HVPG and PSPG). However, these procedures are invasive, and either LSM or SSM may be a non-invasive alternative.</p> <p>Aim: We aimed to investigate the relationship between LSM or SSM and HVPG/PSPG and examined the diagnostic accuracy for identification of clinically significant PH (≥10 mm Hg) or severe PH (≥12 mm Hg).</p> <p>Methods: A retrospective study (IRB Protocol #19230) allowed us to identify patients who had who undergone portal pressure measurements (HVPG or PSPG). A total of 36 patients also had SSM values. Of these, 29 patients carried a hepatic cause of PH, while the remaining had pre-hepatic (n=4) and post-hepatic (n=3) etiology.</p> <p>Results: The median age was 58 years (range: 25-71) with 52% male and 83% with cirrhosis. The median LSM and SSM were 35.7 kPa (range:7.4-75.0, normal ≤7.0 kPa) and 43.8 kPa (range: 20.7-100, normal ≤ 21.0 kPa). Both LSM (r = 0.42, P-value = 0.02) and SSM (r = 0.45, P-value: 0.01) correlated significantly with HVPG/PSPG. The diagnostic accuracy for both LSM and SSM for clinically significant PH was good for LSM (AUROC 0.76, 95% CI:0.58-0.94) and excellent for SSM (AUROC: 0.81, 95% CI:0.65-0.98). The diagnostic accuracy of LSM and SSM was lower for severe PH [AUROC 0.71 (P-value = 0.06) and 0.67 (P-value = 0.1) for LSM and SSM, respectively].</p> <p>Conclusion: Both LSM and SSM correlate with portal pressure measurements and provide diagnostic accuracy to identify patients with clinically significant, but not severe, PH.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Yasmin A. Ali, Paul M. Haste, Raj Vuppalanchi, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27882Investigating Post-Operative Refractive Outcomes in Patients Undergoing Cataract Surgery to Assess the Potential Impact of a Concurrent Diagnosis of Dry Eye Disease (DED)2023-12-13T10:53:18-05:00Ateik AlmalahiBarbara Schroeder<p>Cataract surgery is one of the most performed surgical procedures in the world. A cataract is defined as opaqueness in the interior of the ocular lens<sup>2</sup>. The exact etiology of cataracts is multifactorial ranging from environmental conditions to biochemical changes induced by aging<sup>3</sup>. The Intraocular lens (IOL) power calculation is an essential part of the pre-operative planning for cataract surgery as it determines the specific IOL that should be utilized for a patient. Keratometry measurements are required for this IOL power calculation, however, DED has been shown to cause inaccurate keratometry measurements<sup>4,5</sup>. We hypothesize that patients with DED undergoing cataract surgery will have a larger deviation from the predicted spherical equivalent (SE) post-operatively.</p> <p>Patients who were over the age of 18 and underwent cataract surgery were included. Patients who had a diagnosis of glaucoma, Herpes Simplex Keratitis, punctual plugs, undergone Laser-Assisted in Situ Keratomileusis (LASIK) surgery, Radial Keratometry, or any form of corneal scarring were excluded from this study as they can negatively impact keratometry measurements.</p> <p>The DED sample had a statistically significant larger SE deviation from the predicted SE compared to the healthy sample (p=0.037). The DED sample also had a statistically significant larger percentage of patients with an SE deviation of 0.50 D or greater (p=0.002). Finally, the DED had a statistically significant older age than the healthy group (p=0.028).</p> <p>The significant difference in age between the healthy sample and the DED sample confirms the significant correlation between age and prevalence of DED the literature has described<sup>6</sup>. The statistically significant increased post-operative SE deviation from predicted SE within the DED sample can be the result of the increased variability in the tear film associated with DED. This can lead to inaccurate keratometry measurements, thus leading to incorrect IOL power calculations.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Ateik Almalahi, Barbara Schroeder, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27884Older Adults and their Experience with Interfacility Transfer2023-12-13T11:34:51-05:00Dillon BilleNancy Glober<p>Background/Objective:<br>Interfacility transfers are an integral part of integrated systems of care in modern healthcare. Many transferred patients are older adults, a particularly vulnerable patient population. Unfortunately, interfacility transfers can result in discomfort during the transport, increased distance from family and home, a significant bill for the ambulance ride, and risk of an accident occurring during transport.</p> <p>Methods:<br>To better understand the experiences of older adults before, during, and after interfacility transfer, cognitive interviews were performed with patients and their caregivers at the bedside of the receiving hospital. A standard set of questions was used to assess multiple aspects of the interfacility transfer process including the consent process at the sending hospital, experience with the transfer, and perceived benefits/harms resulting from the transfer.</p> <p>Results:<br>21 patients and 14 caregivers were interviewed in this study and five themes were present throughout these conversations. These themes included, a perceived lack of participation in the decision to be transferred, failed expectations at the receiving hospital, and greater trust in trauma centers like Methodist Hospital.</p> <p>Conclusion:<br>Our interviews demonstrate a greater need for thorough consent for transfer at sending hospitals discussing the realistic outcomes and risks that can be expected from interfacility transfer. With these conversations patients and their caregivers can be empowered to make informed decisions about their care and will likely be more satisfied with the care that they receive and know what to expect during their treatment.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Dillon Bille, Nancy Glober, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27887The Effects of Extracellular Matrix Allograft Administration on Knee Inflammation Following an Anterior Cruciate Ligament Injury in Mice2023-12-13T11:41:28-05:00Caroline BicePeyton EstesBen LoflinRoufael HannaStephen Schlecht<p>Background and Hypothesis:<br>A human placental-derived extracellular matrix (ECM) allograft has previously been developed and is indicated by the manufacturer for reducing tissue inflammation and accelerated repair. To evaluate the efficacy of this product for reducing post-anterior cruciate ligament (ACL) injury inflammation, we used a novel murine in vivo ACL injury model. This model has previously been shown to induce significant synovitis, infrapatellar fat pad (IFP) fibrosis, and articular cartilage (AC) degradation within 2 weeks following an ACL injury. We hypothesized that intra-articular injections of the allograft would correspond with a decrease in synovitis, fibrosis, and articular cartilage degradation.</p> <p>Experimental Design or Project Methods:<br>Ten-week-old C57BL/6J mice were randomly placed into 4 groups (n=10/group). For all mice, the right ACL was ruptured. One group served as sham controls, with a single intra-articular saline injection 24-hours following injury. The remaining three groups received 1, 2, and 6 allograft injections respectively beginning 24-hours after injury. Mice were euthanized 14 days after injury. Following euthanasia, the degree of IFP fibrosis, knee synovitis, and AC degradation were histopathologically evaluated.</p> <p>Results:<br>Thus far, 5 mice per group have been analyzed. Within this subset of mice, those that received 6 injections demonstrated a significantly higher synovitis score (p < 0.01) than the sham group. The 1-injection (p < 0.01), 2-injection (p = 0.16), and 6-injection (p = 0.03) groups each displayed greater IFP fibrosis, relative to sham. No significant differences were found in AC degeneration across groups.</p> <p>Conclusion and Potential Impact:<br>If the current results hold, following the analyses of the remaining mice, then this particular orthobiologic may not be suitable for reducing the post-ACL injury inflammatory response in mice. However, there are several limitations to this pilot study that will first need to be accounted for to confirm the lack of efficacy found.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Caroline Bice, Peyton Estes, Ben Loflin, Roufael Hanna, Stephen Schlecht, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27889The Quandary of Cellular Fractionation — Optimizing Ambion™ Paris System to Advance HPV16 Cancer Research2023-12-13T11:49:32-05:00Emma BischCaylin BillingsleyRachel A. Katzenellenbogen<p>Background and Hypothesis: Human Papillomavirus (HPV) is the causative agent in nearly all cervical cancer cases. It has been shown that the HPV type 16 E6 protein interacts directly with the host protein NFX1-123. Short-term studies have shown that NFX1-123 remains in the cytoplasm; however, it has not been investigated whether NFX1-123 actually translocates to the nucleus in the long term. We hypothesize that over time, NFX1-123 translocates to the nucleus of the cell in long term cultures with 16E6. This present study seeks to optimize the Ambion<sup>TM</sup> Paris system to allow for pure, proper separation of the cytoplasmic and nuclear cellular compartments.</p> <p>Project Methods: Three biologically unique backgrounds of human foreskin keratinocytes (HFKs) were cultured in a monolayer tissue culture dish. Using the Ambion<sup>TM</sup> Paris system, proteins were isolated as whole cell extracts, or nuclear and cytoplasmic fractions. For one lysis method, only protease inhibitors were added to the lysis buffers of the Ambion<sup>TM</sup> Paris system. For another lysis method, 1% NP-40 and protease inhibitors were added to the lysis buffers of the Paris system. Protein lysate concentrations were quantified, then purity of subcellular lysates was determined by western blotting. Histone H3 and GAPDH were used to identify nuclear and cytoplasmic compartments, respectfully.</p> <p>Results: Western blotting confirmed that adding 1% NP-40 to the lysis reagents of the Ambion<sup>TM</sup> Paris kit optimized subcellular fractionization.</p> <p>Potential Impact: Being able to efficiently separate the cytoplasmic and nuclear compartments will allow for accurate identification of NFX1-123 localization during long-term HPV16 infection. If NFX1-123 is found to move into the nucleus under the influence of HPV 16E6, then this could indicate potential transcriptional regulatory functions of the NFX1-123 protein during HPV infection, which is unique from its function in non-infected cells.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Emma Bisch, Caylin Billingsley, Rachel A. Katzenellenbogen, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/2789012 Month vs 6 Month Follow-up Colonoscopy After Piecemeal Endoscopic Resection of Large Nonpedunculated Colorectal Lesions2023-12-13T11:56:51-05:00Michael BobayRachel LahrJeremiah ShultzDouglas Rex<p>Background and aims:<br>Current colonoscopy guidelines recommend nonpedunculated lesions ≥20mm in size and removed piecemeal should have follow-up colonoscopy in 6 months to ensure complete resection. Some data suggest that a 12-month follow-up may be safe and effective for selected lesions. Standard follow-up is 6, 18, 54 and 114 months after piecemeal resection. If the first follow-up visit is 12 months, the sequence is 12, 48, and 108 months. We investigated whether planned 12-month follow-up colonoscopy is as safe and effective for selected lesions when compared to 6-month follow-up.</p> <p>Methods:<br>We utilized a prospectively collected database of 1599 consecutive, large, and nonpedunculated colorectal lesions referred to an expert colonoscopist at a tertiary center. Lesions were removed by endoscopic mucosal resection and assigned a follow-up interval based on their size, histology, and the need to resect additional synchronous lesions identified during the index colonoscopy at our center. Pedunculated polyps (n=158), no follow-up at our center (n=553), follow-up outside of 2 to 36 month reference range (n=10), no polyp or benign growth (n=81), patients referred to surgery for cancer (n=64), and inability to endoscopically resect the lesion (n=24), were excluded from this analysis. Polyp size, location, removal method, endoscopic mucosal resection (EMR) utilization, and lesion pathology were compared to reduce confounding factors.</p> <p>Results:<br>Lesions assigned to a 12-month surveillance interval (n=151) had a smaller mean size (19.48mm +- 7.59 vs. 34.32mm +- 17.84), were more likely to have serrated histology (n=69 (45.70%) vs. n=62 (11.85%), and more likely to be resected en bloc (n=31 (20.53%) vs. n=31 (5.93%) compared to lesions assigned to a 6-month surveillance interval. Of the 151 lesions assigned to a 12-month surveillance interval, 11 (7.3%) had recurrence and none had cancer at follow-up. Among 523 lesions assigned to a 6-month surveillance interval, 53 (10.1%) had recurrence and 1 had cancer at follow-up. Among 65 lesions ≥ 20 mm resected piecemeal and assigned to a 12-month surveillance interval, 8 (12.31%) had recurrence and none had cancer at follow-up.</p> <p>Conclusion and Potential Impact:<br>These results support a 12-month surveillance interval after piecemeal resection of selected large, nonpedunculated, colorectal lesions. Initial 12-month surveillance results in fewer colonoscopies, lower cost, and less inconvenience to patients.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Michael Bobay, Rachel Lahr, Jeremiah Shultz, Douglas Rex, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27891Efficacy of Novel Bracing for Treating Sciatica and Cadaveric Dissection to Examine Excursion of the Sciatic Nerve2023-12-13T12:03:49-05:00Kyle CallahanDale Dellacqua<p>Background/Objective:<br>Sciatica affects nearly half of all Americans and can often become debilitating, leading to severe pain that can limit performing activities of daily living. Brace application has not been tried for alleviation of pain. In this study, we seek to find if a novel brace can decrease pain and decrease bothersome level of symptoms for those suffering from sciatica. In addition, this study utilizes a cadaveric dissection to understand how the sciatic nerve stretches and tensions upon lower limb manipulation.</p> <p>Methods:<br>Fourteen patients self-reported pain, functionality, and bothersome levels pre- and post-bracing. Excel’s data analysis tool was utilized to run statistical tests. One cadaver (2 lower limbs) was dissected, revealing the sciatic nerve at the hip and knee, while tibial nerve at the ankle. Excursion was measured utilizing a fixed pin and an initial distance, the leg manipulated, and final distance from pin measured. Ultimately, excursion was deemed final distance minus initial distance from the pin.</p> <p>Results:<br>The brace decreases Visual Analogue Scale (VAS) scores, increases Patient Reported Outcomes, and decreases Sciatica Bothersome Indexes. There was a significant difference in VAS pre- versus post-brace values at initial and 7-day post-visit but not at 21- or 42-day postvisit. Sciatic nerve excursion was greatest at the ankle.</p> <p>Conclusion and Potential Impact:<br>Brace use decreases pain levels, increases functionality, and decreases bothersome level of symptoms. The distal nerve moves more upon manipulation and therefore is more prone to tensioning than the proximal nerve. Dissection data illustrates how the brace positions the limb in a way that promotes “detensioning” of the nerve, alleviating sciatica. More cadaver data is needed.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Kyle Callahan, Dale Dellacqua, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27893Evaluation of the Relationship Between Collagen Matrix Damage and Proteoglycan Activity Following Submaximal Fatigue Loading2023-12-13T12:10:27-05:00Peyton EstesCaroline BiceBen LoflinTaeyong AhnRoufael HannaStephen Schlecht<p>Background and Hypothesis:<br>Previous research indicated that fatigue loading of the anterior cruciate ligament (ACL) leads to disruption and unraveling of the collagen triple helix structure. Using a novel in vivo murine model, we have spectroscopically shown that collagen unraveling at the molecular level is associated with an increase in proteoglycan activity. Moreover, we found an increase in tissue compliance within these damaged tissue domains. We hypothesize that the increase in proteoglycan activity is largely responsible for this mechanical change. To investigate this, we first need to identify the proteoglycan(s) responsible for our biochemical spectra that indicated<br>an elevation in activity associated with unraveled collagen domains. For this pilot project, we histomorphometrically investigated the proteoglycan activity of two potential protein candidates (decorin, versican) following sub-maximal ACL fatigue loading.</p> <p>Experimental Design or Project Methods:<br>The right knees of 20 mice underwent 5,000 cycles of moderate or strenuous fatigue loading. Left knees served as a control. Samples were collected 1 and 72 hours after loading. Immunohistochemistry was performed to detect decorin and versican activity in the ACLs.</p> <p>Results:<br>A greater area of the ACL was stained with decorin relative to versican in ACLs that underwent moderate fatiguing after 1-hour rest (p = 0.02) and 72-hour rest (p < 0.01). Similar differences were found in ACLs after strenuous fatiguing and 72-hour rest (p < 0.01). No significant temporal differences were found in versican (p = 0.76) or decorin (p = 0.53) activity in fatigued ACLs relative to controls.</p> <p>Conclusion and Potential Impact:<br>These preliminary findings suggest that versican nor decorin are the proteoglycans colocalizing with unraveled collagen. We are currently investigating aggrecan, lumican, and biglycan as other potential proteoglycan candidates to explain our spectroscopic data.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Peyton Estes, Caroline Bice, Ben Loflin, Taeyong Ahn, Roufael Hanna, Stephen Schlecht, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27894Analysis of Perioperative Events in Bilateral vs Unilateral Staged Percutaneous Nephrolithotomy2023-12-13T12:16:54-05:00Kyle EdwardsThomas SheltonMarcelino Rivera<p>Introduction: Kidney stones are a common medical condition that impact approximately 10% of US population. Management of stone disease is based on size and location of stones. Percutaneous nephrolithotomy (PCNL) is typically indicated in patients with large renal stone burden (typically >2 cm) or complex anatomy. In the setting of complex stones, multiple, staged PCNLs are required. We hypothesize that there is no significant difference in the perioperative change in lab values in bilateral PCNLs compared to unilateral PCNLs.</p> <p>Methods: The data was gathered by retrospectively reviewing the electronic medical record of 50 patients in the IU health system who underwent planned staged PCNLs between January and December 2018. We identified patients who underwent both bilateral and unilateral staged procedures. Data for BMI, sex, ethnicity, hemoglobin, estimated glomerular filtration rate (GFR) (typically formula CKD-EPI or MDRD), urine and stone cultures, stone composition, and bilaterality vs. unilaterality was collected. Two-tailed T-tests were performed to analyze data between bilateral and unilateral cases.</p> <p>Results: We identified a total of 50 patients, 19 men vs. 31 women; 9 men and 10 women underwent bilateral PCNLs, while 11 men and 20 women had unilateral PCNLs. BMI ranged from 14.2 to 62.3, and age ranged from 15 to 81. Significant differences were found between the changes in hemoglobin levels in patients who underwent bilateral PCNLs when compared to unilateral PCNLs (p value 0.018). No significant differences were noted when comparing changes of estimated GFR, BMI, age or any other variables.</p> <p>Conclusion: Patients who underwent bilateral staged PCNLs demonstrated a greater drop in perioperative hemoglobin compared to unilateral PCNLs without an increase in blood transfusion. This finding suggests that Bilateral PCNLs requiring multiple stages are safe in complex stone patients.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Kyle Edwards, Thomas Shelton, Marcelino Rivera, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27895Precision analysis of protein sequence and post-translational modification heterogeneity in pancreatic cancer induced cachexia2023-12-13T12:24:32-05:00Allyse M. EmmelTara S. UmbergerEmma H. DoudTeresa A. ZimmersAmber L. Mosley<p>Background and Hypothesis:<br>Cachexia is a wasting syndrome commonly occurring in cancer patients that cannot be explained by decreased calorie intake alone. It results in decreased quality of life and increased mortality, and there are currently no effective treatments. To better understand cachexia, we aimed to profile protein heterogeneity seen in pancreatic ductal adenocarcinoma (PDAC) mouse models with cachexia. Since muscle is a readily available protein resource during catabolism, we hypothesize there are significant changes in protein sequence and post-translational modifications (PTMs) of muscle proteins during cachexia progression. As these proteins are scavenged, precise analysis of sequence variation can identify the exact mechanism of protein/muscle breakdown and better elucidate the molecular processes of PDAC-induced cachexia.</p> <p>Experimental Design:<br>We performed bioinformatic analysis of two proteomics datasets of cardiac and skeletal muscle samples from PDAC-induced cachexia mouse models. Two proteomics software algorithms, SEQUEST (within Proteome Discoverer (PD)) and PEAKS (a machine-learning algorithm), were used to identify all sample proteins and their PTMs. Because PEAKS can identify more PTMs than PD, we compared the most abundant proteins identified in PD and PEAKS, hypothesizing PEAKS would yield greater protein sequence coverage. Finally, we compiled unpublished PTMs and protein processing events for 25 of the most abundant proteins in both datasets.</p> <p>Results:<br>Notably, PEAKS reported greater sequence coverage for cardiac muscle than PD, while the skeletal muscle sample had similar coverage in both algorithms. This discrepancy may suggest cachectic processes degrade skeletal muscle at a greater rate than cardiac muscle, preventing PEAKS from increasing skeletal muscle sequence coverage relative to PD. In addition, several unpublished modifications, including those of actin and acetyl-CoA acetyltransferase, were recorded.</p> <p>Potential Impact:<br>These newly discovered protein modifications may indicate previously unknown molecular processes in the course of PDAC-induced cachexia. These modifications may serve as cornerstones of future research to identify novel therapeutic targets in cachexia treatment.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Allyse M. Emmel, Tara S. Umberger, Emma H. Doud, Teresa A. Zimmers, Amber L. Mosley, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27896Utility of Cardiac POCUS in the Evaluation of Pediatric Chest Pain in the Emergency Department2023-12-13T12:34:09-05:00Connor EmsleyBenjamin NtiPamela C. Soriano<p>Background/Objective:<br>Chest pain in children is rarely caused by a life-threatening pathology. Despite the rarity of potentially life-threatening disease, most children presenting to EDs are evaluated with chest radiographs and laboratory tests without yielding helpful information that significantly changes immediate management. While the utilization of cardiac Point-of-Care Ultrasound (POCUS) by adult emergency physicians has become standard of practice, the data in pediatric emergency departments (PED) is not as robust. This study aims to describe practice patterns in the evaluation of pediatric chest pain presenting in a PED and determine clinical outcomes.</p> <p>Methods:<br>We reviewed charts of previously healthy children aged <18 years old who presented to Riley Children’s Hospital from January 2019 to July 2020 with a chief complaint of chest pain. Patients with known medical history, prior evaluations by a pediatric cardiologist, transfers from other hospital with existing workup were excluded. Patient demographics, laboratory tests and imaging ordered while in the ED, electrocardiography (EKG), consults with subspecialties, disposition and follow up plans were analyzed. We categorized clinical significance of PED interventions as minor, moderate, or major.</p> <p>Results:<br>Out of three hundred and nineteen patients included in the study, 79.6% (254) received chest radiographs, 93.4% (298) underwent EKG, and 4.1% (13) received cardiac POCUS. The findings of these orders prompted minor interventions in 92.8% (296) of patients, moderate<br>intervention in 4.7% (15) of patients, and major intervention in 2.5% (8) of patients.</p> <p>Conclusion and Implications:<br>These results show a lack of use for POCUS in pediatric patients presenting with chest pain while chest radiography is preferred in the ED. Additionally, POCUS did not result in any moderate or major significant clinical outcomes.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Connor Emsley, Benjamin Nti, MS, MD, Pamela C. Soriano, MD, MBAhttps://journals.iupui.edu/index.php/IMPRS/article/view/27897Ankyloglossia and its Importance in Sustained Breastfeeding2023-12-13T12:42:37-05:00Chelsea FathauerDanielle TingleySarah Burgin<p>Ankyloglossia, commonly known as tongue-tie, is reported to affect 7% of infants and can impact ability to breastfeed. A comprehensive review of literature was taken which included an assessment of which diagnostic tools are most accurate in determining ankyloglossia associated with difficult breastfeeding. It was noted that there was not a standardized approach<br />to identifying and treating ankyloglossia in breastfed infants. Based on this review, a multidisciplinary team was established to develop a team for a holistic assessment of breastfeeding efficacy. A protocol was developed for assessment of frenotomy impact on breastfeeding. It included LATCH, Coryllos Scale, and IBFAT as the most useful evaluation tools and developed a prospective assessment in infants with ankyloglossia. This study is in the early data collection phase. The goal of this study is to fill an important gap in the knowledge of the impact of ankyloglossia in sustained breastfeeding.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Chelsea Fathauer, Danielle Tingley, Sarah Burgin, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27898Social Determinants of Health and 30-Day Readmissions in an Urban Community Hospital in Northwest Indiana2023-12-13T12:52:54-05:00Eric GonsiorowskiMichael YallourakisJonathan GuerreroBaraka Muvuka<p>Background: Hospital readmission within 30 days of discharge is a quality of care indicator with implications for healthcare systems, payers, and patients. The Hospital Readmission Reduction Program enacted in 2012 aimed to reduce preventable readmissions. Yet in 2018, there were 3.8 million adult 30-day readmissions with an average rate of 14% and estimated cost of $15,200 per readmission. This study examined the influence of social determinants of health (SDOH), demographics, and health behaviors on 30-day readmissions at an urban hospital in Northwest Indiana. This is part of a Community-Based Participatory Research (CBPR) partnership between Indiana University School of Medicine-Northwest and St. Mary Medical Center (SMMC) to address SDOH.</p> <p>Methods: This retrospective study analyzed a limited dataset generated by SMMC in EPIC™ with SDOH, demographics, health behaviors, and health outcomes measures from inpatient admissions between January 2021 to March 2023. Data analysis consisted of descriptive, bivariate (Chi-Square; p<0.05), and multivariate (binary logistic regression; p<0.05) analyses in SPSS 29.0. This study was exempted by the Indiana University Human Research Protection Program (IRB #14040).</p> <p>Results: The sample consisted of 7445 patients, majority 65 years and above (56.5%), white (77.47%), and publicly insured (76.83%). 30-day readmissions represented 10.5% of admissions. The bivariate analysis revealed statistically significant associations between 30-day<br>readmissions and age (p<0.001), language (p=0.008), insurance type (p<0.001), veteran status (p=0.017), and smoking (p<0.001). The multivariate analysis found that age (OR=1.008; p=0.004), being a non-English speaker (OR=1.866; p=0.009), public insurance (OR=2.096; p<0.001), and former smoking (OR=1.243; p=0.011) remained significantly associated with 30-day readmission.</p> <p>Conclusions: Social and behavioral factors were associated with 30-day readmissions in an urban community hospital. Incorporating SDOH and behavioral interventions into hospital readmission reduction programs may reinforce these programs. The upcoming CBPR phase will conduct advanced analysis on these findings to uncover new relationships relevant to SMMC’s objectives.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Eric Gonsiorowski, Michael Yallourakis, Jonathan Guerro, PharmD, BCPS, MSEd, Baraka Muvuka, PhD, MPHhttps://journals.iupui.edu/index.php/IMPRS/article/view/27899Incidence of Venous Thromboembolism and Hematoma Following Placement of Inflatable Penile Prosthetic: Safety of Perioperative Subcutaneous Heparin2023-12-13T12:58:57-05:00Jacob GoodHelen Bernie<p>Background/Objective: Patients undergoing inflatable penile prosthetic (IPP) surgery are at an increased risk for cardiovascular complications such as venous thromboembolism (VTE) following surgery due to pre-existing comorbidities associated with erectile dysfunction. The use of perioperative subcutaneous heparin (SqH) along with a surgical drain has been shown to be effective in preventing VTE in IPP patients, without increasing hematoma formation. Not all prosthetic surgeons utilize surgical drains postoperatively. In this study we aim to assess the safety and efficacy of perioperative SqH in preventing VTE in IPP patients without the use of a surgical drain.</p> <p>Methods: This was a retrospective review from January 2021-July 2023 of patients who underwent IPP placement or explant and replacement at a single institution. Patient demographics, comorbidities, Caprini risk factor scores, VTE risk factors, and 90-day postoperative complications, including hematoma formation, were reviewed. Statistical analyses were performed comparing these variables in men who received SqH and those who did not.</p> <p>Results: We reviewed data for 240 patients; 53% (n=127) received perioperative SqH. The incidence of VTE was 0.9% (1/113) in the non-SqH group, and no VTE was recorded in the group receiving SqH. There was no statistical significance in hematoma formation between<br>groups (SqH 5.5% vs. non-SqH 6.2% p=.898). Beyond hypertension prevalence (SqH 74.8% vs. non-SqH 62.8% p=.045), there was no difference between comorbidities or Caprini risk factor scores (SqH 6.79 vs. non-SqH 6.82 p=.474) between groups (Table 1). 94% of the<br>patients in this study were considered high risk for VTE.</p> <p>Conclusions: Perioperative SqH use without placement of a surgical drain was found to be safe and effective in preventing VTE in patients undergoing IPP surgery. There was no increased risk of hematoma formation or post-operative complications between the groups. Perioperative SqH should be considered in all patients undergoing IPP surgery.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Jacob Good, Helen Bernie, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27900Viability of Transplanted De Novo Retinal Ganglion Cells in Human Donor Eyes Maintained Under Elevated Intraocular Pressure2023-12-13T13:02:55-05:00Salil J. GuptaShahna Shahul HameedTasneem Sharma<p>Purpose: Glaucoma is a group of optic neuropathies characterized by visual field loss, classically due to increased intraocular pressure (IOP) and retinal ganglion cell (RGC) degeneration. Current treatment options reduce IOP, but RGC degeneration persists. De novo<br>RGCs can be differentiated from reprogrammed human corneal fibroblasts and transplanted into the retina to potentially restore vision in patients with late-stage disease when most RGCs are irreversibly damaged. We investigate the survival of these human induced pluripotent stem cell (IPSC) derived RGCs after culturing them in human donor eyes under conditions of elevated and normal IOP using the ocular translaminar autonomous system (TAS) chamber.</p> <p>Methods: Human iPSCs were generated by reprogramming human donor corneal fibroblasts using Sendai viral vectors with Yamanaka factors. These iPSCs were then differentiated into retinal organoids from which RGCs were obtained. The RGCs were transduced with AAV2-GFP and transplanted into donor human eyes obtained from control individuals. They were pressurized for approximately 5 days, with the left eye maintained at normal IOP and right eye at elevated IOP. Viability was measured by expression levels of pro-survival pathways via qRTPCR, immunohistochemistry staining, and electroretinography for retinal function (ERG).</p> <p>Results: We successfully transplanted human RGCs into human donor eyes and visualized them after GFP transduction. We maintained a pressure differential between the two eyes for approximately 5 days using the TAS model. Differential expression of survival, inflammatory and apoptotic genes was identified between normal and high IOP. We identified retinal function changes under normal and high IOP after RGC transplantation.</p> <p>Conclusions: Human iPSC derived RGCs provide a potential strategy to overcome vision loss in patients with diseases that damage RGCs such as glaucoma, Parkinson’s, Alzheimer's, multiple sclerosis, and traumatic optic neuropathy. Future investigation would involve integration of transplanted RGCs and directing their axons towards visual centers in the brain.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Salil J. Gupta, Shahna Shahul Hameed, Tasneem Sharma, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27901Assessment of IL-9/IL-9R Expression and Therapeutic Effect of IL-9 Blockade in a Mouse Breast Cancer Model2023-12-13T13:07:30-05:00Amir HailatJilu ZhangMark H. Kaplan<p>Background and Hypothesis:<br>IL-9 is a cytokine produced by TH9, mast cells, and innate lymphoid cells. IL-9 acts on the IL-9 receptor (IL-9R) and is primarily involved in parasitic immunity and allergic inflammation. IL-9 has anti-tumor effects in solid tumors such as melanoma. IL-9 also has pro-tumor effects in various cancer types, including lung cancer. Previous studies have shown that increased serum IL-9 in breast cancer patients correlates with tumor metastasis. Therefore, we hypothesize that IL9 signaling contributes to breast tumor metastasis and blocking IL-9 may have a therapeutic benefit in reducing metastasis.</p> <p>Methods:<br>Mice were orthotopically implanted with 4T1 breast tumor cells. Organs were harvested after 28 days. Total RNA was extracted and expression of <em>IL-9/IL-9R</em> and leukocyte markers were assessed. To test therapeutic effect of IL-9 blockade, tumor-bearing mice were treated with anti-IL-9 monoclonal antibody (αIL-9). Tumor sizes were monitored every 4 days. On day 28, tumor tissue was harvested and weighed. Lung was also harvested and stained with H&E for metastasis analysis.</p> <p>Results:<br>Primary tumor growth was not altered by αIL-9. The effect of αIL-9 treatment on lung metastasis is pending pathological analysis. We further examined IL-9R to define how tumor burden alters expression of <em>IL-9</em> and <em>IL-9R</em> across tissues. Lymphoid organs, such as the thymus, spleen, and inguinal lymph node (inguinal LN), exhibit high levels of IL-9R. Additionally, the small intestine is notably enriched with IL-9R. The thymus exhibited the highest <em>IL-9</em> expression.</p> <p>Conclusion and Future Directions:<br>Although blockade of IL-9 did not impact tumor growth in this model, this will be examined in other models to confirm the findings. Further research is needed to investigate the potential therapeutic benefits of αIL-9 with other established therapies. We observed that there is altered IL-9 and IL-9R expression in tumor bearing mice and the physiological significance of that finding remains to be determined.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Amir Hailat, Jilu Zhang, PhD, Mark H. Kaplan, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27902The Role of SHROOM3 in Congenital Heart Disease2023-12-13T13:13:48-05:00Grant HammonsAlly AldrichRebecca DouglasCatherine GuilfoyNina J. JainAshleigh McMullanPrincess MurrayCaelen RathkeMark WakulchikEllen VoskoboynikJames B. ZwierzynskiMatthew Durbin<p>Background and Hypothesis: Congenital heart defects (CHD) are the most common, and most frequently fatal birth defects, but most etiology remains unknown. We identified a patient with CHD and implicated a gene called SHROOM3. SHROOM3 binds Dishevelled2 which is the central cytoplasmic component of both canonical and noncanonical Wnt/planar cell polarity (PCP) signaling pathways. PCP drives cell movement and is important to embryogenesis and disruption causes CHD. We hypothesize CHD can result from SHROOM3-loss-of-function due to PCP disruption.</p> <p>Project Methods: To interrogate SHROOM3’s role in CHD and PCP we utilized an established <em>in vivo</em> SHROOM3-loss-of-function model, <em>Shroom3</em> gene trap mice (<em>Shroom3<sup>gt</sup></em>). We also utilized a loss-of-function model for PCP membrane component VANGL2, (<em>Vangl2<sup>+/-</sup></em>). We assayed genetic interaction between Shroom3 and Vangl2 during cardiac development by crossing singly heterozygous null mice to produce compound heterozygous embryos, harvested embryos, and performed histologic analysis for cardiac defects. We also utilized a human <em>in vitro</em> SHROOM3-loss-of-function model, a CRISPR-Cas9 edited SHROOM3 knockout HELA cell line. We assayed cell movement using a scratch assay.</p> <p>Results: Compound heterozygous <em>Shroom3<sup>+/gt</sup></em>;<em>Vangl2<sup>+/-</sup></em> embryos had a three fold increase in heart defects compared to singly heterozygous <em>Shroom3<sup>+/gt</sup></em>;<em>Vangl2<sup>+/+</sup></em> or <em>Shroom3<sup>+/+</sup></em>;<em>Vangl2<sup>+/-</sup></em> embryos (3 of 19 or 15.7%, versus 1 of 17 or 5.2%, and 1 of 19 or 4.8%, respectively), demonstrating a trend towards genetic interaction between SHROOM3 and VANGL2/PCP during cardiac development. The scratch assays demonstrated cell movement defects due to SHROOM3-loss-of-function consistent with increased cell movement.</p> <p>Conclusion and Potential Impact: We demonstrate SHROOM3 interacts with Wnt/PCP during cardiac development. Further interrogation of SHROOM3’s role in Wnt signaling will provide insight into the mechanisms by which a novel CHD candidate participates in cardiogenesis and will improve CHD diagnosis, management, and therapeutic development.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Grant Hammons, Ally Aldrich, Rebecca Douglas, Catherine Guilfoy, Nina J. Jain, Ashleigh McMullan, Princess Murray, Caelen Rathke, Mark Wakulchik, Ellen Voskoboynik, James B. Zwierzynski, Matthew Durbin, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27903Abdominal Aortic Aneurysm Response to Interleukin-10 Hydrogel-Based “Bio-Ink” Therapy in Rodent Models2023-12-13T13:36:56-05:00Olivia JimenezTheresa DoironStone ChenAli SualehJennifer StashevskyMackenzie MadisonChang-Hyundai GilNicanor MoldovanSteve MillerMichael Murphy<p>Abdominal Aortic Aneurysms (AAA) are the pathological expansion of the aorta, which can rupture and cause significant mortality. Approximately 200,000 AAA cases occur annually in the US, with more than 15,000 cases resulting in death. Risk factors for AAA are similar to those of cardiovascular disease states, particularly cigarette smoking, and AAA patients are generally elderly, Caucasian males. Currently, no medical therapy exists for AAA outside of surgical intervention. We previously hypothesized that the early initiation and propagation of stages in AAA development are inflammatory driven. This process results in a weaker aortic wall, which<br>we have evidenced through increased elastin breakdown products and inflammatory markers in AAA patients in comparison to matched controls. This project investigated the use of a novel anti-inflammatory hydrogel to ameliorate AAA progression.</p> <p>Our study uses a gelatin-based biodegradable bio-ink containing the anti-inflammatory cytokine interleukin-10 (IL-10), which was applied to the aorta with a novel hydrogel extruding “BIOPENCIL” device. We used a previously described rodent model consisting of intra-luminal injection of elastase in the infrarenal aorta combined with topical application of calcium chloride; alternatively, topical calcium chloride was used alone for AAA development. The BIOPENCIL was used to deliver the hydrogel containing IL-10 or control at the time of AAA creation. The animals were euthanized 14 or 21 days post-procedure and evaluated for AAA volume, surface area, and diameter alongside molecular analyses to evaluate for immunological changes between control and treatment groups. We predict that the rodent groups treated with IL-10 will not have AAA expansion, while the control group will see AAA expansion. This is based on<br>longitudinal data from weekly ultrasounds and will be confirmed with microCT.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Olivia Jimenez, Theresa Doiron, Stone Chen, Ali Sualeh, Jennifer Stashevsky, Mackenzie Madison, Chang-Hyundai Gil, Nicanor Moldovan, Steve Miller, Michael Murphy, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27904Using Botulinum Toxin for the Treatment of Gastroparesis (GP) for the selection of Patients with Higher Clinical Success, Improved Quality of Life (QOL), and Improved Social Functioning Post Gastric Peroral Endoscopic Myotomy (GPOEM)2023-12-13T13:45:58-05:00Amr KaisMohammad A. Al-Haddad<p>Background/Objective:<br>While G-POEM remains an effective and exciting treatment for GP patients, predictors of clinical success remain poorly characterized. Botox injection of the pylorus prior to committing to GPOEM can help differentiate those who might have a favorable clinical response to this procedure in patients with GP.</p> <p>Methods:<br>To evaluate the utility of Botox injection prior to G-POEM, 124 patients with clinically diagnosed GP who underwent a GPOEM were assessed in this retrospective cohort study. All G-POEM procedures were conducted at a single center and were completed between February 2018 and May 2023. Patients who had received intrapyloric Botox injection (n=79) had QoL and clinical success rates compared to patients who received other treatment options (n=45). Results were assessed at 1-, 3-, 6-, 12-, 24-, 36-, 48-months post G-POEM.</p> <p>Results:<br>When assessing symptom severity, the difference between the change in GCSI values for Botox patients and patients receiving other prior therapy was statistically significant at 6 months post-GPOEM; +1.27 for Botox patients vs +0.55 for other treatments (p-value of 0.03). At this 6-month checkpoint, 64% of the Botox group achieved clinical success compared to 37.5% for the other treatment group. When comparing QoL, intrapyloric Botox injection has statistically significant improvements in SF-36 total score at 1, 3-, 6-, 12-, and 36-months post G-POEM, while patients receiving other treatments had no statistically significant improvements in their SF-36 total scores.</p> <p>Conclusion:<br>We hypothesize that clinical improvement on pre GPOEM Botox selects patients with a higher component of pyloric spasm who end up responding more favorably to G-POEM.</p> <p>Scientific/Clinical/Policy Impact and Implications:<br>Intrapyloric Botox injection is technically feasible in almost all patients with GP and does not require special expertise, training, or equipment; therefore, this should be strongly considered prior to referring a patient for G-POEM.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Amr Kais, Mohammad A. Al-Haddad, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27905Assessing Skin Sympathetic Nerve Activity and Cardiac Effects in Patients with Gastric Electrical Stimulation2023-12-13T13:52:37-05:00Tejas KandharkarMatthew WardAnita GuptaThomas NowakThomas H. Everett, IV<p>Background:<br>Gastric Electrical Stimulation (GES) is a therapy for gastroparesis patients, alleviating symptoms like nausea, vomiting, and poor gastric emptying. The therapeutic impact of GES is believed to stem from changes in autonomic nerve activity, particularly parasympathetic activity via the vagal nerves. This study examines skin sympathetic nerve activity (SKNA) to assess autonomic nerve bursts, investigating the effects of GES on nerve activity and cardiac function.</p> <p>Methods:<br>SKNA signals were recorded from 48 patients at three locations: left side of the neck (SKNA1), right side of the neck (SKNA2), and via ECG Lead 1 across the chest (SKNA3). Signals were band pass filtered (500 Hz to 1000 Hz) to eliminate ECG and muscle artifacts and highlight nerve activity. Using Labchart software, the absolute value integral (iSKNA) was calculated for each 100-millisecond sample, with resulting values exported to Excel. Data was collected during different GES conditions: GES On, GES at ½ voltage, GES Off, and GES back on. The threshold for nerve activity bursts was determined as the mean of iSKNA values + two times the standard deviation in each section.</p> <p>Results:<br>Histograms of average aSKNA values showed reduced nerve activity with GES off. Left and vagal nerve activity on SKNA1 was significantly lower with GES fully on or off compared to GES at ½ voltage. No other significant differences were observed in variabilities or average aSKNAs in SKNA1 or SKNA2.</p> <p><br>Future Directions & Potential Impact:<br>Burst analysis of iSKNA data will address key questions. Variations in burst activity with different GES conditions may elucidate GES's therapeutic effects on gastroparesis. Subsequent segmentation of data into patients with resolved and unresolved symptoms could reveal the relationship between burst activity and therapeutic efficacy. Additionally, correlation of burst data with heart rate variability analysis will provide insights into the impact of GES on cardiac function. This study will advance our understanding of GES effects and safety, potentially improving patient outcomes.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Tejas Kandharkar, Matthew Ward, Anita Gupta, Thomas Nowak, Thomas H. Everett, IV, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27906Prophylactic Posterior Targeted Muscle Reinnervation (TMR) Approach in Below Knee (BKA) Amputation Settings2023-12-13T13:59:06-05:00Sri Charan KanthalaCameron HarmonJeffrey GrossJoshua AdkinsonBrian Christie<p>Background/Objective: Targeted muscle reinnervation (TMR) is a nerve reconstruction technique focused on improving phantom limb pain (PLP), residual limb pain (RLP), prosthesis function, and limiting neuroma formation. In below-knee-amputations (BKA), TMR performed "through-the-wound" is heavily documented. Alternatively, the "posterior approach" was developed to help increase visibility of peripheral nerves from the posterior fossa. This study focuses on the surgical efficiency and patient outcomes of the posterior approach compared to the through-the-wound approach. We hypothesize the posterior approach will be comparable to<br>or improve time-to-prosthesis fitting, OR time, and pain scores.</p> <p>Methods: 157 patients underwent TMR at two hospitals in Indianapolis, IN, and were identified using CPT 64890. 39 patients underwent posterior approach TMR post-BKA. Data on demographics, follow-up/rehabilitation visits, post-operative complications, prosthesis fitting, and total OR time were collected. Additionally, 32 patients received TMR "through-the-wound", and total OR time, post-operative complications, and time-to-prosthesis fitting were tracked. Patient-reported outcome (PRO) surveys are being sent to patients pending IRB approval.</p> <p>Results: Of the 39 who received the posterior approach between 1/10/2020 and 4/6/2023, 25 received TMR in the right leg and 14 in the left. Following BKA, average time to TMR was 144 days. However, 18 patients received TMR directly after undergoing BKA (46.2%). Average OR time for acute and delayed posterior TMR patients was 208.06 minutes and 199.47 minutes, respectively. 10 patients reported post-operative complications (25.6%): dehiscence (12.8%) or infection (7.7%). 23 patients received prosthesis fitting on average 3 months post-op. Average OR time and time-to-prosthesis fitting for "through-the-wound" TMR surgeries were 192.84<br>minutes and 5.81 months, respectively.</p> <p>Potential Impact: Posterior approach TMR had no significant impact on OR time, but time-to-prosthesis fitting significantly decreased. Once PRO surveys return, average long-term PLP and RLP can be determined. Preliminarily, posterior approach TMR improves aspects of patient outcomes while not compromising surgical efficiency.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Sri Charan Kanthala, Cameron Harmon, Jeffrey Gross, Joshua Adkinson, Brian Christie, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27907Exploring the Influence of tGLI-1 on Temozolomide Resistance in Glioblastomas: Unraveling Novel Therapeutic Targets2023-12-13T14:06:40-05:00Hannah von WerderHaddie DeHartRichard Carpenter<p>Background/Objective:<br>Temozolomide (TMZ) is a standard chemotherapy treatment for patients with glioblastoma (GBM), but its effectiveness is limited, with only 50% of patients initially responding and developing resistance over time. Glioma stem cells (GSCs) have been implicated in TMZ resistance, particularly the mesenchymal subtype. The truncated form of GLI1, known as tGLI1, is highly expressed in mesenchymal GSCs and has been associated with poor patient outcomes in GBM. However, the role of tGLI1 in TMZ resistance remains unknown.</p> <p>Methods:<br>The GBM cell line, U87MG, was utilized for this study. The IC50 of TMZ was determined using a cell viability assay. After successful transfection with vector, GLI1, and tGLI1, the cells were treated with the IC50 of TMZ to assess changes in cell viability between the groups.</p> <p>Results:<br>The IC50 of TMZ is 290.1 μM, as averaged between replicate assays. Thus far, the results showed that tGLI1-expressing cells exhibited significantly higher cell viability (average: 39.09%) compared to Vector (average: 26.78%) and GLI1 (average: 27.11%). However, the tGLI1 group displayed higher variability in cell viability results, as evidenced by a larger standard deviation (0.2758) and standard error (0.1592) compared to vector (SD: 0.0325, SE: 0.0188) and GLI1 (SD: 0.1354, SE: 0.0781). The One-Way ANOVA, followed by Tukey's Multiple Comparison Test, results showed no statistically significant differences in cell viability between the groups.</p> <p>Conclusion/Impact:<br>The increased cell viability observed in tGLI1-expressing cells suggests a potential association between tGLI1 and TMZ resistance, warranting additional research to fully comprehend its impact on GBM treatment response. Further investigation and replication studies are needed to establish the robustness of these results. This knowledge may contribute to the development of<br>targeted therapies aimed at inhibiting tGLI1 or its downstream signaling pathways, potentially<br>improving the response to TMZ and patient outcomes.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Hannah von Werder, Haddie DeHart, Richard Carpenter, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27932Characterization of a Novel Mutation in the COPI Vesicle on Binding to Dilysine Motifs2023-12-18T11:22:11-05:00Kimberly FelipeSara CusterElliot J. Androphy<p><strong>Background/Objective:</strong> The heptameric COPI coatomer complex is involved in the formation of vesicles and the intracellular trafficking of proteins between the Golgi and Endoplasmic Reticulum as well as throughout the cytoplasm. Members of the COPI complex bind dilysine motifs found in the C-terminal domain of the cargo protein, particularly KKxx or KxKxx. We generated a point mutation in the WD40 domain of the COPI alpha subunit (⍺-COP). We hypothesized that the E269V mutant ⍺-COP would not co-immunoprecipitate (co-IP) COPI cargo proteins terminating with a dilysine domain of KxKxx (Nucleolin and Stasimon/Tmem41b), but would bind cargo proteins terminating in KKxx (FLAGSyntaxin17). We predicted that a mutation in the ⍺-COP C-terminus, which impairs interaction with ε–COP, would not affect its ability to co-IP dilysine-containing cargo.</p> <p><strong>Experimental Design or Project Methods:</strong> HEK-293TT cells were transfected with Myctagged wild-type, E269V, and triple mutant (3X) ⍺-COP. The E269V ⍺-COP mutant has an amino acid change at position 269 from glutamic acid to valine. The triple ⍺-COP mutant has three amino acid changes that eliminate binding with the ε–COP COPI subunit. Transfected ⍺-COP was immunoprecipitated using magnetic anti-Myc beads. Endogenous Nucleolin was immunoprecipitated using magnetic Protein A beads conjugated to rabbit polyclonal anti- Nucleolin antibody. Western blots of inputs and immunoprecipitates of each experiment were conducted to determine the ability of ⍺-COP to co-IP C-terminal dilysine-containing proteins.</p> <p><strong>Results:</strong> Endogenous Nucleolin and Stasimon co-immunoprecipitated with WT and 3X ⍺-COP, but not E269V ⍺-COP.</p> <p><strong>Conclusions and Potential Impact:</strong> The inability of mutation E269V to co-IP dilysine proteins implies that the WD40 domain of the COPI ⍺-COP protein is required for binding to KxKxxterminating proteins, as typified by Nucleolin and Stasimon.The C-terminal 3X mutation shows that ε-COP is not necessary for dilysine recognition and implies that ⍺-COP directly binds to this KxKxx motif.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Kimberly Felipe, Sara Custer, Elliot J. Androphy, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27933Modeling Breast Cancer in Men2023-12-18T11:53:08-05:00Benjamin FischerAditi S. KhatpePoornima Bhat-NakshatriHarikrishna Nakshatri<p><strong>Background:</strong> In 2023, 2,800 men are expected to be diagnosed with breast cancer in the United States, and while it affects a smaller patient population, breast cancer in men has a 19% higher mortality rate. Even though 87% of male breast cancers are estrogen receptor positive (ER+), breast cancer in men is resistant to anti-estrogen therapies. In this study we set out to characterize the difference between male and female breast epithelial cells to elucidate potential treatment pathways.</p> <p><strong>Project Methods:</strong> We compared male and female epithelial cell lines from ultrasound guided breast biopsies of healthy men and women from the Susan G. Komen Tissue Bank that were processed using a culturing method developed in the lab. RNA-Seq of breast epithelial cells was done to identify unique signaling networks and genes in men, and RT-qPCR was used to determine the expression of ER signaling associated genes including ESR1, TBX3, FOXA1, GATA3 and APOBEC3B. Immunofluorescence for ERα was done to characterize differential expression and localization between men and women.</p> <p><strong>Result:</strong> RNA-Seq identified an upregulation of ESR1 which correlates with increased ER+ male breast cancer, along with upregulation of non-genomic ER signaling pathway, including SRC activation, which may affect treatment response. Male cells also showed high levels KDM5D which is implicated in immune system evasion in esophageal cancer and colon adenocarcinoma. RT-qPCR displayed a two-fold increase in ESR1 and increases in TBX3 and APOBEC3B. Immunofluorescence identified ERα and localization to the cell membrane in men.</p> <p><strong>Conclusion:</strong> This first characterization and modeling of men’s breast epithelial cells provides the basis for determining the mechanism behind the lack of efficacy of anti-estrogen therapeutics. With further investigation of the increased non-genomic ER signaling in men, specifically the SRC pathway, we hope this will provide a pathway to treat male breast cancer through potential combination therapies.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Benjamin Fischer, Aditi S. Khatpe, Poornima Bhat-Nakshatri, Harikrishna Nakshatri, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27934Neutrophil-to-Lymphocyte Ratio (NLR) to Monitor Neuroinflammation Status During Long COVID2023-12-18T12:05:36-05:00Luke FisherBenecia GokaJessica PaterFen-Lei Chang<p><strong>Background/Objective:</strong> 480 million people have been infected with COVID-19 worldwide. Roughly 10-15% of these patients will develop Long COVID which causes an array of symptoms including fatigue and “brain fog”. Currently, a reliable marker to monitor Long-COVID has not been established. NLR (neutrophil/lymphocyte ratio) has been shown to be an economical, reliable, and easily obtainable blood biomarker to monitor systemic inflammation. Our study aimed to use NLR to monitor Long COVID patients across pre-COVID to 24 months after acute COVID.</p> <p><strong>Methods:</strong> A retrospective patient chart review of 831 patients from a tertiary community hospital Post-COVID Clinic was completed to assess the changes in NLR. Symptoms and demographic information were collected.</p> <p><strong>Results:</strong> Our studies showed that at the time of acute COVID, NLR was elevated to 5.22+/-0.50 from the baseline pre-COVID NLR of 2.67+/-0.14. 4 to 6 months after the acute phase of COVID, the NLR was normalized to 2.61+/-0.20 which gradually re-elevated to 3.58+/-0.39 from 16-24 months after the acute COVID (p < .01) indicating a re-activation of systemic inflammation. At 16-24 months after the acute COVID, 66% of patients with elevated NLR were hospitalized during acute COVID, while 33% of patient with normal NLR were hospitalized (Chi Square=3.90; p<0.05).</p> <p><strong>Conclusion:</strong> Our findings support the potential connection between the sustained Long COVID symptoms with sustained elevation of NLR, a marker of systemic inflammation reactivation. Currently we are building a non-COVID control group with the expansion into a prospective study phase. If our findings can be validated with further studies, NLR may be a useful biomarker for future monitoring of disease progression and marker for treatment development.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Luke Fisher, Benecia Goka, Jessica Pater, Fen-Lei Chang, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27935Factors Affecting Patient Reported Outcomes Following Tibial Plateau Fracture2023-12-18T13:31:09-05:00Luke HaagErin McCoySohum PatelJames SlavenLuke LopasRoman Natoli<p><strong><span data-contrast="auto">Background/Objective:</span></strong><span data-ccp-props="{"201341983":0,"335559739":160,"335559740":259}"> </span></p> <p><span data-contrast="auto">Tibial Plateau Fractures (TPFs) account for ~1% of all fractures and ~8% of all fractures in the elderly. Despite the frequency and severity of TPFs there is a paucity of data evaluating factors that affect patient recovery after injury and surgical fixation. We hypothesized that patient reported outcomes are modulated by several variables including patient demographics, comorbidities, injury characteristics, and Social Determinants of Health (SDH). </span><span data-ccp-props="{"201341983":0,"335559739":160,"335559740":259}"> </span></p> <p><strong><span data-contrast="auto">Methods:</span></strong><span data-ccp-props="{"201341983":0,"335559739":160,"335559740":259}"> </span></p> <p><span data-contrast="auto">In this retrospective cohort study, we collected the interval patient reported outcome scores (PROs) of patients with TPFs treated with open reduction internal fixation occurring between February 2013 and November 2020. PROs included 1) Visual Analog Scale (VAS) pain scores, 2) Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference (PI) scores, and 3) Physical Function (PF) survey scores. Patient demographics, comorbidities, fracture characteristics, insurance status, and area deprivation index (ADI) of the patient’s residence were collected via electronic medical record review. Bivariate analyses of PRO scores to the aforementioned factors were performed using generalized estimating equations to account for participant repeated measures, with p<0.05 being considered significant.</span><span data-ccp-props="{"201341983":0,"335559739":160,"335559740":259}"> </span></p> <p><strong><span data-contrast="auto">Results:</span></strong><span data-ccp-props="{"201341983":0,"335559739":160,"335559740":259}"> </span></p> <p><span data-contrast="auto">196 patients were evaluated with >1 year follow-up. It was determined that patients’ insurance status affected their VAS (p0<.001), PI (p<0.001), and PF (p<0.001) scores. Patient ADI affected VAS (p<0.001) and PI (p=0.0026), with increased ADI scores resulting in worse PROs. Diabetes and depression were found to negatively impact VAS (p=0.010 & 0.008 respectively) and PI (p=0.0044 & 0.0048, respectively). Additionally, age and sex both influence VAS (p=0.0006 & 0.0033, respectively), and compartment syndrome was associated with decreased PF (p=0.0206). </span><span data-ccp-props="{"201341983":0,"335559739":160,"335559740":259}"> </span></p> <p><strong><span data-contrast="auto">Conclusion and Potential Impact:</span></strong><span data-ccp-props="{"201341983":0,"335559739":160,"335559740":259}"> </span></p> <p><span data-contrast="auto">To our knowledge, this is the first investigation to evaluate the effect of SDH on patient recovery following surgical fixation of TPFs—suggesting that insurance status and residence ADI scores are associated with worsened PROs. Further investigation is necessary to identify if these factors are independent of other covariates.</span><span data-ccp-props="{"201341983":0,"335559739":160,"335559740":259}"> </span></p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Luke Haag, Erin McCoy, Sohum Patel, James Slaven, Luke Lopas, Roman Natoli, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27936Maternal IVIG Administration in Rhesus Alloimmunized Pregnancies: A Systematic Review2023-12-18T13:36:57-05:00Anna FloodEnaja SambaturHiba Mustafa<p><strong>Background:</strong> Rhesus (Rh) alloimmunization occurs when an Rh negative mother is exposed to red blood cells (RBC) from an Rh positive fetus. The mother develops antibodies in the current pregnancy that attack Rh positive fetus in subsequent pregnancy, causing hemolytic disease of the fetus and newborn (HDFN). RhD is the most common antigen to result in fetal anemia requiring intrauterine transfusions (IUT). Although the traditional method of management and highly effective, IUTs carry significant risk particularly when performed early in gestation, potentially resulting in procedure-related fetal deaths. Intravenous immunoglobulin (IVIG) therapy may postpone or even replace invasive intrauterine treatment in fetuses of mothers with severe alloimmunization in previous pregnancies.</p> <p><strong>Objective:</strong> To evaluate whether maternal administration of IVIG in high-risk Rhesus alloimmunized pregnancies is effective in delaying the need for IUTs as well as delaying the onset of severe fetal anemia and thus in diminishing its clinical consequences.</p> <p><strong>Study design:</strong> A systematic literature search was conducted for maternal intravenous immunoglobulin administration in pregnancies with Rh isoimmunization in the following databases: Medline, Embase and Cochrane Library from 1946 to 2 February 2023. Inclusion criteria was studies done during pregnancy in which IVIG was administered to the mother in Rh alloimmunized pregnancies/fetal anemia. All non-english papers, animal papers, systematic reviews, editorials and studies in which IVIG was administered to non-pregnant patients were excluded. Data was extracted from these full texts and analyzed for inclusion based on the quantity of usable data and patient information. Extracted data included maternal antibody type and titer, number of maternal IVIG administrations, number of IUTs, and fetal Hb levels prior to first IUT and at delivery. Time interval (weeks) between IVIG and first IUT was also included in the extracted data along with gestational age at delivery. Individual patient data extraction was done for studies that provided data.</p> <p><strong>Results:</strong> 16 studies were included in data analysis. Analysis of extracted data is ongoing.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Anna Flood, Enaja Sambatur, Hiba Mustafa, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27937The Role of Sociogenomics on Chronic Wounds 2023-12-18T13:44:31-05:00John HajjKanhaiya SinghChandan K Sen<p><strong><span data-contrast="none">Background and Objective:</span></strong><span data-ccp-props="{"134233117":true,"134233118":true,"201341983":0,"335559740":276}"> </span></p> <p><span data-contrast="none">Chronic wounds affect almost 2.5% of the United States population. Along with substantial healthcare costs, other factors like reduced employment opportunities and social isolation further complicate the patient’s quality of life. Socioeconomic status (SES) has been shown to influence gene expression that can increase susceptibility and deterioration of chronic wounds. Our study looks to identify genes that have been impacted by SES in chronic wound patients. Exploring this association can enhance understanding of the relationship between SES and chronic wound outcomes.</span><span data-ccp-props="{"134233117":true,"134233118":true,"201341983":0,"335551550":6,"335551620":6,"335559740":276}"> </span></p> <p><strong><span data-contrast="none">Experimental Design:</span></strong><span data-ccp-props="{"134233117":true,"134233118":true,"201341983":0,"335559740":276}"> </span></p> <p><span data-contrast="none">A cohort of 72 chronic wound patients were recruited. Patient demographics and socioeconomic backgrounds were collected. Blood DNA isolation was performed and allotted for genetic analysis by</span> <span data-contrast="none">Axiom™ Precision Medicine Diversity Array (PMDA). DNA genotyping data was obtained, and single nucleotide polymorphisms (SNP) markers pertaining to wound healing were studied. </span><em><span data-contrast="none">P</span></em><span data-contrast="none"> < 0.05 were used to designate significant SNP marker mutations in the cohort.</span><span data-ccp-props="{"134233117":true,"134233118":true,"201341983":0,"335551550":6,"335551620":6,"335559740":276}"> </span></p> <p><strong><span data-contrast="none">Results:</span></strong><span data-ccp-props="{"134233117":true,"134233118":true,"201341983":0,"335559740":276}"> </span></p> <p><span data-contrast="none">To add strength to our project, we have chosen to further study the results obtained by our group </span><span data-contrast="none">(</span><a href="https://doi.org/10.18060/27205"><span data-contrast="none">https://doi.org/10.18060/27205</span></a><span data-contrast="none">), </span><span data-contrast="none">which has previously found significant SNPs associations of the </span><em><span data-contrast="none">vitamin D receptor</span></em><span data-contrast="none"> (</span><em><span data-contrast="none">VDR</span></em><span data-contrast="none">) and the </span><em><span data-contrast="none">methylenetetrahydrofolate reductase</span></em><span data-contrast="none"> (</span><em><span data-contrast="none">MTHFR</span></em><span data-contrast="none">) genes in chronic wound patients. Using PMDA, our analysis showed polymorphisms in </span><em><span data-contrast="none">CYP24A1</span></em><span data-contrast="none"> (</span><em><span data-contrast="none">p</span></em><span data-contrast="none"> = 0.0072), a gene involved in vitamin D metabolism, and </span><em><span data-contrast="none">MTHFR </span></em><span data-contrast="none">(</span><em><span data-contrast="none">p</span></em><span data-contrast="none"> = 0.00625), a gene involved in folate and homocysteine metabolism. </span><span data-contrast="none">Modifications of these genes have been associated with pathogenesis to impaired wound healing.</span><span data-ccp-props="{"134233117":true,"134233118":true,"201341983":0,"335551550":6,"335551620":6,"335559740":276}"> </span></p> <p><strong><span data-contrast="none">Conclusion:</span></strong><span data-ccp-props="{"134233117":true,"134233118":true,"201341983":0,"335559740":276}"> </span></p> <p><span data-contrast="none">There is a need for further investigation into health outcomes and their association with SES. Our study aims to address the knowledge gap in this field by focusing on chronic wound healing in relation to socioeconomic status. With our results, we hope to emphasize the importance of sociogenomics, and how it can be utilized to advocate for improved patient outcomes across all socioeconomic backgrounds.</span><span data-ccp-props="{"134233117":true,"134233118":true,"201341983":0,"335551550":6,"335551620":6,"335559740":276}"> </span></p> <p><span data-ccp-props="{"134233117":true,"134233118":true,"201341983":0,"335559740":276}"> </span></p> <p><strong><span data-contrast="none">Acknowledgements:</span></strong><span data-ccp-props="{"134233117":true,"134233118":true,"201341983":0,"335559740":276}"> </span></p> <p><span data-contrast="none">This project was funded, in part, with support from the Indiana Clinical and Translational Sciences Institute funded, in part by UL1TR002529 from the National Institutes of Health (NIH). The presented work is also supported by NIH grants R01DK135447 and R01DK128845 to CKS. The laboratory of KS is supported by DoD grant W81XWH-22-1-0146. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. </span><span data-ccp-props="{"134233117":true,"134233118":true,"201341983":0,"335551550":6,"335551620":6,"335559740":276}"> </span></p>2024-01-11T00:00:00-05:00Copyright (c) 2023 John Hajj, Kanhaiya Singh, Chandan K Sen, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27938Association of Socio-Demographic Factors, Social Determinants of Health, and Weekly Physical Activity in an Urban Hospital in Northwest Indiana2023-12-18T13:44:50-05:00Wael GadBrianna ChandlerBrendan JonesBaraka MuvukaJonathan GuerreroJoshua Mangum<p><strong>Background:</strong> Engaging in regular physical activity has been proven to have beneficial health effects such as preventing chronic diseases and improving mental health. Recent studies have demonstrated correlations between socio-demographic factors and physical activity levels. This study determined the associations between socio-demographic factors, social determinants of health and the amount of weekly physical activity in patients occupying an urban underserved area.</p> <p><strong>Methods:</strong> This study retrospectively analyzed a dataset generated by St. Mary Medical Center from EPIC™ with demographic characteristics and physical activity levels partitioned by time per week for adult inpatient visits from January 2021 to March 2023. Patients were stratified into physical activity levels based upon published guidelines: inactive (no physical activity), insufficiently active (<150 minutes per week) or sufficiently active (≥150 minutes per week). Data analysis was conducted in SPSS 28.0 using tests of association including Kruskal Wallis H and multivariate ordinal regression model. This study was exempted by Indiana University Human Research Protection Program (IRB # 14040).</p> <p><strong>Results:</strong> The sample of individuals from the dataset who answered physical activity questions was comprised of 1498 patients. There was a statistically significant difference in physical activity level by age group (p<0.001), sex (p<0.05), insurance category (p<0.001), and social connections risk score (p<0.001); with race (p=0.057) and language (p=0.054) approaching significance. Multivariate analysis showed that age was the only significant factor when accounting for all variables, with higher age groups reporting lower proportions of physically active individuals.</p> <p><strong>Conclusion:</strong> Determining how socio-demographic factors influence physical activity levels will direct efforts to form and implement new interventions in the Northwest Indiana urban area and support community health initiatives. This data makes it possible to inform practitioners of the demographics that are at risk of being insufficiently active and having them direct those patients to programs in place to help bridge the lapse.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Wael Gad, Brianna Chandler, Brendan Jones, Baraka Muvuka, Jonathan Guerrero, Joshua Mangum, MS, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27939Assessing Prevalence of TBI in a Community Setting 2023-12-18T13:51:10-05:00Pranav HaranAllie Thomas-Fannin<p><strong><span data-contrast="auto">Background</span></strong><span data-contrast="auto">: Traumatic brain injury (TBI) is often under-reported and thus under-recognized by clinicians. Reports of TBI prevalence have been widely variable based on the methods of data collection and definition of TBI. This study investigates the prevalence of TBI using the Ohio State University TBI Identification Method (OSU TBI-ID), a reliable and valid structured interview designed to elicit lifetime history of TBI. We also assessed relationships between TBI and psychiatric illnesses. Identifying prevalence and effects of TBI on mental health is critical to providing personalized, higher-quality care for psychiatric patients in community settings.</span><span data-ccp-props="{}"> </span></p> <p><span data-ccp-props="{}"> </span></p> <p><strong><span data-contrast="auto">Methods</span></strong><span data-contrast="auto">: Patients receiving mental health care at the IUSM Psychiatry Residency Clinic in Vincennes, Indiana were asked to participate in a research study assessing history of head or neck injuries. Patients attended their regularly scheduled appointments with resident physicians, and 2–5-minute TBI screenings were conducted during or immediately after their appointment. Following the interview, patient charts were reviewed for documentation of prior TBI and all current psychiatric diagnoses. </span><span data-ccp-props="{}"> </span></p> <p><span data-ccp-props="{}"> </span></p> <p><strong><span data-contrast="auto">Results</span></strong><span data-contrast="auto">: Prevalence of TBI was reported at 62.3% among patients receiving psychiatric care. 87 total TBI events were recorded, including repetitive TBI events, after 77 patient interviews. The most common cause of acute TBI was vehicular accident. The most common cause of repetitive TBI was sports injury. Of the 87 TBIs, only 5 TBI events were recorded in patient charts. History of TBI was more likely in patients with PTSD as well as substance use disorders, and this was especially evident in patients with repetitive TBI. </span><span data-ccp-props="{}"> </span></p> <p><span data-ccp-props="{}"> </span></p> <p><strong><span data-contrast="auto">Conclusion and Potential Impact</span></strong><span data-contrast="auto">: This study shows that TBI is quite common among psychiatric patients and is vastly under-reported in patient charts. Increasing clinician awareness of TBI history in their patients is critical to providing high-quality care, and the OSU TBI-ID provides an efficient way to screen patients for TBI.</span><span data-ccp-props="{}"> </span></p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Pranav Haran, Allie Thomas-Fannin, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27940Impact Of Connective Tissue Matrix Products and Critical Size Defects on Gut Microbiota and Fracture Healing in Mice 2023-12-18T13:55:47-05:00Alexander HarrisAshlyn MorrisWill VarnerReggie ParkerMurad NazzalAmy CreecySonali J. KarnikRachel J. BlosserElizabeth ScottHannah WangTyler MargettsMarko DragisicUpasana GangulyJill C. FehrenbacherFletcher A. WhiteJessica Hathaway-SchraderMelissa A. Kacena<p><strong>Abstract: </strong></p> <p>Approximately 6.2 million people in the USA alone suffer from some form of fracture annually. Depending on the intensity of trauma and complexity of the fractures, some fractures will not heal without medical intervention. It is imperative to develop novel therapies that target fracture healing. Connective Tissue Matrix (CTM) Biomedical is a company that develops human placenta, amnion, chorion, and other umbilical derived allograft products which may provide a solution to the problem of impaired fracture healing. CTM products contain structural proteins, cytokines, and growth factors that may have regenerative and anti-inflammatory properties. Although these products are already used clinically for fracture and wound healing in humans, no pre-clinical studies exist verifying their efficacy or mechanism of action.</p> <p>Commensal microbiota is a collection of microorganisms such as bacteria, fungi, and viruses. Disruption of the gut microbiota, known as gut dysbiosis, can lead to a variety of disorders in other tissues. In fact, new studies indicate that alterations in the gut microbiota can affect bone health. This is likely due to impaired nutrient uptake and an increase in inflammation from bacterial byproducts that are not favorable to a healthy gut ecosystem. More recent studies indicate that the microbiota is also implicated in fracture healing.</p> <p>Our study aims to investigate if CTM products have a positive effect on fracture healing by affecting the gut microbiota composition and bacteriome. To test this, critical sized defects (CSD) were induced in mice and treated with various CTM implants or saline control. Fecal samples were taken on the day of surgery and weekly thereafter. Bacterial DNA was subsequently extracted from these samples and analyzed using PCR. We anticipate seeing changes in load and composition of gut bacteria following CSD surgery.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Alexander Harris, Ashlyn Morris, Will Varner, Reggie Parker, Murad Nazzal, Amy Creecy, Sonali J. Karnik, Rachel J. Blosser, Elizabeth Scott, Hannah Wang, Tyler Margetts, Marko Dragisic, Upasana Ganguly, Jill C. Fehrenbacher, Fletcher A. White, Jessica Hathaway-Schrader, Melissa A. Kacena, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27941Microplastic Identification and Quantification in Biological Samples 2023-12-18T14:18:08-05:00Kennedy HelmsKimberly GettisAbigail HallAlexei ChristodoulidesNathan J. Alves<p><strong><span data-contrast="auto">Background</span></strong><span data-ccp-props="{"201341983":0,"335559739":160,"335559740":259}"> </span></p> <p><span data-contrast="auto">The convenience and durability of plastics has made it a staple in the manufacturing industry, but without adequate recycling, these plastics are filling landfills at an alarming rate. This plastic waste is broken down into micro- and nano-plastics that have been found in both marine and terrestrial environments. The potential ramifications of accumulating plastic particles in the environment are of urgent attention as humans are exposed to these particles through ingestion, inhalation, and dermal exposure. Due to the lack of consensus of the effect microplastics have on the coagulation cascade, our aim was to form clots under various conditions so that a comparison can be drawn.</span><span data-ccp-props="{"201341983":0,"335559739":160,"335559740":259}"> </span></p> <p><strong><span data-contrast="auto">Methods</span></strong><span data-ccp-props="{"201341983":0,"335559739":160,"335559740":259}"> </span></p> <p><span data-contrast="auto">We utilized varying sizes (500-2,000 nm) and concentrations (25-250 µg/ml) of non-functionalized polystyrene (nPS) microplastics to characterize their effect on clot size, strength, and anatomy using ex-vivo shear flow clot formation of human whole blood via a Chandler loop apparatus. Additionally, we studied the effect of fluorescent Nile red dye (NR, ex/em: 545/625 nm) on clotting dynamics and visualization of microplastic particles via fluorescence microscopy. </span><span data-ccp-props="{"201341983":0,"335559739":160,"335559740":259}"> </span></p> <p><strong><span data-contrast="auto">Results</span></strong><span data-ccp-props="{"201341983":0,"335559739":160,"335559740":259}"> </span></p> <p><span data-contrast="auto">Ex-vivo clots were made (422 s</span><span data-contrast="auto">-1</span><span data-contrast="auto"> shear at increasing nanoplastic concentrations), sectioned, and utilized for quantification optimization in histological processing to preserve plastic integrity and fluorescent signal. NR-dyed microplastics were shown to produce sufficient fluorescent signal for imaging. Images were taken at various magnifications (4x-40x) and exposure times (100µs-500ms) using brightfield and fluorescent microscopy (Cy3 filter) on a Nikon Eclipse Ni microscope and a Nikon DS-Ri2 Microscope camera.</span><span data-ccp-props="{"201341983":0,"335559739":160,"335559740":259}"> </span></p> <p><strong><span data-contrast="auto">Potential Impacts</span></strong><span data-ccp-props="{"201341983":0,"335559739":160,"335559740":259}"> </span></p> <p><span data-contrast="auto">These results highlight the need for further analysis of the effects of microplastics on the coagulation cascade, as well as further optimization of techniques used to identify and quantify microplastics in complex biological samples.</span><span data-ccp-props="{"201341983":0,"335559739":160,"335559740":259}"> </span></p> <p><span data-ccp-props="{"201341983":0,"335559739":160,"335559740":259}"> </span></p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Kennedy Helms, Kimberly Gettis, Abigail Hall, Alexei Christodoulides, Nathan J. Alves, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27942A Predictive Model for Cardiomyopathy Progression in a Longitudinal Cohort of DMD Patients2023-12-18T14:24:51-05:00Alexa M. JaureguiConner C. EarlLarry W. Markhamonathan H. SoslowCraig J. Goergen<p><strong><span data-contrast="none">Background: </span></strong><span data-contrast="none">Cardiomyopathy (CM) is currently the leading cause of mortality in patients with Duchenne muscular dystrophy (DMD). DMD CM is asymptomatic during the early stages of disease and age of onset and clinical progression vary. We previously showed that 4D kinematic analysis of cardiovascular magnetic resonance (CMR) imaging is a robust method to visualize strain and function changes in DMD patients. Our objective, using 4D CMR image analysis, is to build a predictive model to quantify disease progression, and predict functional decline as measured by left ventricular ejection fraction (LVEF) in a longitudinal cohort of DMD patients.</span><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p> <p><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p> <p><strong><span data-contrast="none">Methods:</span></strong><span data-contrast="none"> We obtained 4D CMR images from 40 DMD patients imaged every 12 months for three years. Localized surface area strain (Ea) values were derived from compiled 4D CMR images. Patient demographics, presence or absence (+/-) of late gadolinium enhancement (LGE) and LVEF were obtained by a trained cardiologist. Principal component analysis was used to identify prominent variables contributing most to variability. These variables, along with clinically relevant variables, were selected to build the predictive model. We built a linear mixed effects model using visit, age, basal E</span><span data-contrast="none">a</span><span data-contrast="none">, and LGE presence. Each patient was considered a random effect to account for variability in initial CM severity.</span><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p> <p><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p> <p><strong><span data-contrast="none">Results: </span></strong><span data-contrast="none">Study patients were grouped into stages of heart failure according to the American Heart Association: Stage A, LVEF>55%, LGE(-); Stage B, LVEF>55%, LGE(+); Stage C, 40%<LVEF<55%, LGE(+); Stage D, LVEF<40%, LGE(+). Linear mixed effects model showed a good prediction of LVEF on year 3 with a root mean squared error of 3.6% and an R</span><span data-contrast="none">2</span><span data-contrast="none"> value of 0.75 (</span><em><span data-contrast="none">p</span></em><span data-contrast="none"><0.0001.).</span><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p> <p><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p> <p><strong><span data-contrast="none">Conclusion: </span></strong><span data-contrast="none">Early detection is crucial for appropriate clinical intervention. This novel predictive model was developed to determine if Ea derived from 4D imaging, LVEF, and (+/-) LGE can be used to predict functional outcomes in DMD CM.</span><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Alexa M. Jauregui, Conner C. Earl, Larry W. Markham, onathan H. Soslow, Craig J. Goergen, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27946Coil-Assisted Retrograde Transvenous Obliteration (CARTO) for the Treatment of Gastric Variceal Bleeding in a Patient with a Gastrorenal Shunt: A Case Report 2023-12-19T09:20:10-05:00Ryan BoldaRamana YedavalliAmy Han<p><strong><span data-contrast="auto">Background</span></strong><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p> <p><span data-contrast="auto">Portal hypertension (pHTN) is primarily caused by liver cirrhosis, which can lead to varices at portosystemic anastomoses.</span><span data-contrast="auto">1,2</span><span data-contrast="auto"> Gastric variceal bleeding (GVB) is rare but can be life-threatening with a mortality up to 50% for each bleeding episode. When endoscopic banding is ineffective and TIPS placement is contra-indicated due to risk of post-TIPS encephalopathy, coil-assisted retrograde transvenous obliteration (CARTO), which has shown great success in some studies, can be an effective treatment.</span><span data-contrast="auto">5,8,9,10</span><span data-contrast="auto"> This case demonstrates successful use of CARTO to treat GVB in a patient with a gastrorenal shunt (GRS) who presented with pHTN.</span><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p> <p> </p> <p><strong><span data-contrast="auto">Case Overview</span></strong><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p> <p><span data-contrast="auto">A 62-year-old female with cirrhosis due to nonalcoholic steatohepatitis (NASH) presented with pHTN and GVB. The patient had a massive GRS, which permitted access through the systemic venous circulation to treat the bleeding varices. Furthermore, the patient had hepatic encephalopathy (HE), making TIPS placement a poor choice due to risk of HE exacerbation. CARTO was performed to treat the bleeding varices and had the added benefit of decreasing risk of HE.</span><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p> <p><span data-ccp-props="{}"> </span></p> <p><strong><span data-contrast="auto">Discussion/Results</span></strong><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p> <p><span data-contrast="auto">This case highlights CARTO in a patient with a 22mm GRS using a dual catheter system. Eighteen detachable 035 coils were first deployed in the GRS, followed by complete occlusion with a Gelfoam slurry to obliterate the gastric varices. Studies have described CARTO, all of which have shown incredibly high technical (complete embolization by angiography and/or CT) and clinical (no variceal rebleeding) success rates. This patient returned for follow-up CT and endoscopic imaging, which confirmed technically and clinically successful CARTO.</span><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p> <p><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p> <p><strong><span data-contrast="auto">Conclusion and Potential Impact</span></strong><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p> <p><span data-contrast="auto">CARTO appears to be a safe alternative to TIPS when treating GVB caused by pHTN, especially in patients who have HE and a GRS. Thus, CARTO should be discussed as a treatment option for these patients. Although portal pressure increases post-CARTO, the improvement of HE can lead to an improved safety profile with future TIPS.</span><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Ryan Bolda, Ramana Yedavalli, MD, MS, Amy Han, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27949Implantation of Flexible Electrodes for Simultaneous in-vivo Extracellular Recording and Two-Photon Imaging2023-12-19T09:37:30-05:00Alec BoothHammad KhanOm KolheKrishna Jayant<p><strong><span data-contrast="none">Introduction:</span></strong><span data-ccp-props="{"201341983":0,"335559739":0,"335559740":276}"> </span><span data-contrast="none">Rigid silicon electrodes like Utah array grids and Neuropixel probes have been used in human and animal brain models to understand the dynamics of neural computation, treat neurodegenerative disorders, and act as brain-machine-interfaces. However, when implanted chronically, glial proliferation can rapidly disrupt the interaction between neurons and electrodes, drastically reducing recording fidelity. The development of flexible electrodes has the potential to minimize tissue damage and inflammation, which allows for long-term recordings over several months. In line with this objective, the Nano-neurotechnology Lab at Purdue University has developed a 6-µm thick, flexible, and biocompatible Parylene probe to facilitate chronic recordings in awake mice. However, flexible electrodes present a unique engineering challenge as the force required to insert into the brain causes the probe to buckle and fail during insertion.</span><span data-ccp-props="{"201341983":0,"335559739":0,"335559740":276}"> </span></p> <p><strong><span data-contrast="none">Methods and Results:</span></strong><span data-ccp-props="{"201341983":0,"335559739":0,"335559740":276}"> </span><span data-contrast="none">Here, I designed a micropipette shuttle using a glass micropipette and custom insertion system which provided reproducible probe implantation into the cortex. The implantation device was designed in CAD software and 3D-printed for rapid prototyping. The procedure was developed on brain phantoms made of 0.6% agarose with a comparable Young’s modulus to mouse brain tissue. Utilizing 3D-printed pieces and the surface tension of diluted poly-vinyl-acrylate adhesive to align the probe to a micropipette, insertion of the electrode and retraction of the shuttle was accomplished in awake mice. </span><span data-ccp-props="{"201341983":0,"335559739":0,"335559740":276}"> </span></p> <p><strong><span data-contrast="none">Conclusion:</span></strong><span data-ccp-props="{"201341983":0,"335559739":0,"335559740":276}"> </span><span data-contrast="none">The implications of flexible recording electrodes are extensive. Long-term implantation opens the door for understanding behavioral and learning dynamics over time. Moreover, the flexibility of these probes allows for the combination of 2-photon optical microscopy, thus enabling multi-modal investigation of neuronal physiology. A low-cost, consistent procedure is the first step in the implementation of these flexible probes for further advancements in fundamental neuroscience research and its potential applications in human and animal studies.</span><span data-ccp-props="{"201341983":0,"335559739":0,"335559740":276}"> </span></p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Alec Booth, Hammad Khan, Om Kolhe, Krishna Jayanthttps://journals.iupui.edu/index.php/IMPRS/article/view/27950The Effects of Integrative Palliative Oncology on Health System Burden 2023-12-19T09:45:04-05:00Jackson BrandonJoseph McCollom<p><strong><span data-contrast="auto">Backgroun</span>d: </strong><span data-contrast="auto">Early integration of palliative care in oncology has been shown to benefit patients on an individual level, especially regarding mood and quality of life. These patients both have a difficult disease course – where palliative care can help with interpersonal, spiritual, physical, and care planning concerns – and represent a substantial burden on inpatient facilities like intensive care units and emergency departments. This study explores relationships between early palliative oncology, patient healthcare experience, and broader burden on the health system.</span><span data-ccp-props="{"201341983":0,"335559739":0,"335559740":276}"> </span></p> <p><strong><span data-contrast="auto">Methods:</span></strong> <span data-contrast="auto">A retrospective chart review was performed comparing oncology patients at Parkview Regional Medical Center in Fort Wayne, IN. Cohort A (200 patients) received palliative care along with standard oncology care while cohort B (200 patients) received standard oncology care alone. Post-diagnosis emergency department visits, inpatient stays, and intensive care unit stays were compared. So were in-hospital deaths, referrals to hospice, and record of advance care planning documents.</span><span data-ccp-props="{"201341983":0,"335559739":0,"335559740":276}"> </span></p> <p><strong><span data-contrast="auto">Results</span></strong><span data-ccp-props="{"201341983":0,"335559739":0,"335559740":276}">: </span><span data-contrast="auto">Two endpoints evaluated by Chi</span><span data-contrast="auto">2</span><span data-contrast="auto"> analysis were statistically significant (p values <0.01): Cohort A was more likely than cohort B to be referred to hospice (79.5% vs 31.5%) and more likely to have advance care planning documents on file (38.5% vs 21%). Additionally, a T-test showed statistically significant difference (p=.001) for inpatient stays post-palliative care encounter versus patients who had no palliative care (1.75 vs 2.41).</span><span data-ccp-props="{"201341983":0,"335559739":0,"335559740":276}"> </span></p> <p><span data-ccp-props="{"201341983":0,"335559739":0,"335559740":276}"> </span><strong><span data-contrast="auto">Conclusion</span></strong><span data-ccp-props="{"201341983":0,"335559739":0,"335559740":276}">: </span><span data-contrast="auto">This study shows correlation between integrated oncology care with patients filing ACP documents and being referred to hospice. Additionally, it finds that cancer patients who visit the palliative care office have fewer inpatient stays after their visit than those who don’t visit at all. </span><span data-ccp-props="{"201341983":0,"335559739":0,"335559740":276}"> </span></p> <p><span data-ccp-props="{"201341983":0,"335559739":0,"335559740":276}"> </span><strong><span data-contrast="auto">Future Implications</span></strong><span data-ccp-props="{"201341983":0,"335559739":0,"335559740":276}">: </span><span data-contrast="auto">Future studies in this area should explore the latter finding from new perspectives, perhaps focusing on the differences between palliative care visit promptly after diagnosis/staging and palliative care implemented long after diagnosis/staging or not administered at all. </span><span data-ccp-props="{"201341983":0,"335559739":0,"335559740":276}"> </span></p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Jackson Brandon, Joseph McCollomhttps://journals.iupui.edu/index.php/IMPRS/article/view/27951Length of Stay Index – A Retrospective Chart Review on In-patient Dermatology Consults 2023-12-19T09:51:59-05:00Cynthia CahyaEdita Newton<p><strong><span data-contrast="auto">Background and Objective: </span></strong><span data-contrast="auto">In monitoring inpatient care quality and efficiency, one metric of interest is Length of Stay (LOS) by diagnosis-related group (DRG) system and how this compares to peer institutions. Vizient Inc. provides a source of such benchmarking - collecting and analyzing individual case-level data from community and academic medical center hospitals nationwide. Using this data, Vizient calculates an expected LOS by DRGs and adjusts for severity of illness and other factors for inter-hospital comparison. Because LOS reduction is an important mechanism for improving outcomes and efficiency of care, The Department of Dermatology would like to understand which dermatologic consults are exceeding the Vizient expected LOS (LOS index > 1). </span><span data-ccp-props="{"201341983":0,"335559739":160,"335559740":276}"> </span></p> <p><strong><span data-contrast="auto">Project Methods: </span></strong><span data-contrast="auto">Consecutive charts of 663 patients with dermatology-related diagnoses in the inpatient setting at IU University and Methodist Hospitals between January 2021 and January 2023 were reviewed. Parameters identified included: category of dermatologic disorder, LOS index, time to consult, and quarter of encounter. Data was organized and analyzed using paired t-tests, linear regression, and descriptive statistics in JMP software.</span><span data-ccp-props="{"201341983":0,"335559739":160,"335559740":276}"> </span></p> <p><strong><span data-contrast="auto">Results: </span></strong><span data-contrast="auto">The mean LOS index for Dermatology inpatient consults was 1.89 (n=469). Patients whose dermatologic diagnosis fell under chronic wound, mechanical, infectious, drug adverse event, autoimmune, neoplasm, inflammatory, vascular, and blistering had a significant increase in observed length of stay compared to expected length of stay (p < 0.05). Time to dermatology consult was not found to correlate to shortening or prolonging LOS index. </span><span data-ccp-props="{"201341983":0,"335559739":160,"335559740":276}"> </span></p> <p><strong><span data-contrast="auto">Potential Impact:</span></strong><span data-contrast="auto"> The data from this review will help direct the Department of Dermatology to the dermatologic consults with the highest need for potential interventions. </span><span data-ccp-props="{"201341983":0,"335559739":160,"335559740":259}"> </span></p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Cynthia Cahya, Edita Newtonhttps://journals.iupui.edu/index.php/IMPRS/article/view/27956Changes in Transport Mode for Pediatric Trauma Patients Before and After the COVID-19 Pandemic2023-12-20T16:43:05-05:00Byoungchan AnJodi L. RaymondMatthew Paul Landman<p><strong><span data-contrast="auto">Background:</span></strong><span data-contrast="auto"> The Emergency Medical Services (EMS) system has faced significant stress due to the COVID-19 pandemic and now workforce issues. This study was performed to evaluate potential changes in pediatric trauma patient transport over that time period. We hypothesized that more trauma patients would use private transportation/personal vehicles to arrive at the ED in the post-pandemic time frame when compared pre-pandemic.</span><span data-ccp-props="{"201341983":0,"335559739":240,"335559740":276}"> </span></p> <p><strong><span data-contrast="auto">Methods:</span></strong><span data-contrast="auto"> This was a retrospective cohort study of patients that were admitted to the Emergency Department of Riley Hospital for Children between 01/01/2017 to 12/31/2022. Patients were excluded if they were transferred from another hospital or had mechanisms of injury including burns, suffocations, drownings, hangings, medical, and ingestions. Pre- and post-COVID patients were defined as admission to the ED before or after March 25, 2020, the day after a stay at home orders were implemented in Indiana. Univariate and multivariate analyses were performed.</span><span data-ccp-props="{"201341983":0,"335559739":240,"335559740":276}"> </span></p> <p><strong><span data-contrast="auto">Results:</span></strong><span data-contrast="auto"> A total of 4,116 patients matching the criteria were identified with 52% arriving after the start of the COVID-19 shut down orders. 30.6% of patients arrived by private operated vehicles (POV) during pre-covid times and 30.3% in the post-covid years (p=0;39). A logistic regression analysis was performed for mortality which demonstrated that transport mode (ground ambulance vs helicopter vs POV) was not statistically associated with mortality rate (OR 0.36, 95% CI 0.12 – 1.10, p=0.07), when controlling for important clinical variables associated with injury severity.</span><span data-ccp-props="{"201341983":0,"335559739":240,"335559740":276}"> </span></p> <p><strong><span data-contrast="auto">Conclusion:</span></strong><span data-contrast="auto"> There was no statistical difference in arrival by POV before and after the COVID-19 pandemic in our cohort. Additionally, there was no significant data to suggest that transport mode was associated with mortality. Further research should be done to assess potential barriers to transport to pediatric trauma centers, particularly considering ongoing EMS workforce strains.</span><span data-ccp-props="{"201341983":0,"335559739":240,"335559740":276}"> </span></p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Byoungchan An, Jodi L. Raymond, Matthew Paul Landman, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27958Trends in Thymic Epithelial Tumor Patients with Comorbid Autoimmune Disease 2023-12-20T17:05:41-05:00Aneesha AnandNikhitha LavuKenneth A. KeslerPatrick J. Loehrer<p><span data-contrast="auto">Thymic epithelial tumors (TETs) are rare malignancies originating from the thymus in the anterior mediastinum. TETs include thymic carcinoma and thymoma. Approximately 30-40% of thymomas have associated autoimmune paraneoplastic disorders, the most common being myasthenia gravis. A broad range of other paraneoplastic syndromes have also been reported. Currently, little is known about demographic or histological trends in thymoma patients with comorbid autoimmune disease. In this single institution retrospective chart review, we assessed the distribution of thymoma-associated paraneoplastic syndromes at the IU Simon Cancer Center (IUSCC) to identify trends within demographic and histological features. We created a database of IUSCC patients seen from 2000-2023 and identified 170 subjects with biopsy-proven malignant TET and associated autoimmune disease. Data was exported to excel and R for analysis. Factors analyzed included: age at diagnosis, sex assigned at birth, BMI, WHO (World Health Organization) classification, and Masaoka staging. Overall survival was also compared to matched controls without paraneoplastic syndrome. A total of 37 different paraneoplastic syndromes were identified in association with thymoma in IUSCC patients. The most prevalent was Myasthenia Gravis (110 patients), followed by Hypothyroidism (21 patients, 5 confirmed as Hashimoto’s thyroiditis), Good Syndrome (19 patients), and Pure Red Cell Aplasia (15 patients). Significant findings included: 36.4% of patients with paraneoplastic comorbidity had >1 paraneoplastic syndrome, 51.8% presented with Stage IV disease, and 40.4% had WHO Type B2 tumor pathology, with Type B3 being second most common (25%). No significant demographic associations were identified. 10-year survival of TET patients with paraneoplastic syndromes was not significantly different from those without (p= 0.721). These results indicate potential associations between thymoma staging and grading and development of paraneoplastic disease. Further analysis with a larger data set is warranted. Serum and blood test analysis may also elucidate reasons behind the development of paraneoplastic disease in thymoma patients.</span><span data-ccp-props="{"201341983":0,"335559739":0,"335559740":276}"> </span></p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Aneesha Anand, Nikhitha Lavu, Kenneth A. Kesler, Patrick J. Loehrer, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27959Familial Adenomatous Polyposis within the Pediatric Hereditary Polyposis Registry 2023-12-20T17:14:31-05:00Brendan AndersonTina Zhang<p><strong><span data-contrast="auto">Background/Objective:</span></strong><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p> <p><span data-contrast="auto">Familial Adenomatous Polyposis (FAP) is a condition characterized by values exceeding hundreds of colorectal adenomatous polyps. FAP has a prevalence of 1 in 8,300 people, demonstrating an autosomal dominant inheritance pattern. This condition follows a pathogenic variation of the Adenomatous Polyposis Coli (APC) gene, located on chromosome 5q21-22. These mutations are heavily correlated with the incidence of colorectal carcinoma, requiring prophylactic colectomy. The management and treatment of FAP requires routine surveillance to reduce gastrointestinal polyp burden. The objective for this study is to characterize the current patient population at Riley with polyposis syndromes and assess clinical surveillance in patients diagnosed with FAP.</span><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p> <p><strong><span data-contrast="auto">Methods:</span></strong><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p> <p><span data-contrast="auto">Historical data from 2020-2022 GI clinical visits were reviewed using the diagnostic codes </span><em><span data-contrast="auto">Family history of colonic polyps, Benign neoplasm of colon unspecified, </span></em><span data-contrast="auto">and </span><em><span data-contrast="auto">Other phakomatoses not elsewhere classified. </span></em><span data-contrast="auto">These criteria identified 93 patients of which 64 patients were diagnosed with a hereditary polyposis syndrome for inclusion within the registry. Of the 64 patients, 42 had a diagnosis of FAP. Clinical data reviewed included the patient’s age of diagnosis, completion of genetic testing and follow-up, surgical treatment, routine endoscopic surveillance, and modes of imaging.</span><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p> <p><strong><span data-contrast="auto">Results:</span></strong><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p> <p><span data-contrast="auto">Results indicated a median age of diagnosis of 10 years, lower than previously reported national averages of 13.5-17 years. Evaluation of routine follow-up indicated a rate of endoscopy at 0.822 scopes per year and demonstrated that abdominal CT scans as well as abdominal X-rays were the most common supplemental modes of imaging.</span><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p> <p><strong><span data-contrast="auto">Conclusion/ Future Directions:</span></strong><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p> <p><span data-contrast="auto">The data from this registry will help direct care of patients with FAP, ensuring they receive treatment in accordance with national guidelines for routine surveillance and prophylactic colectomy. Moving forward, the intention is to expand the registry's date range to incorporate more patients and elaborate further on endoscopic findings for the specific <span class="TextRun SCXW60355319 BCX2" lang="EN-US" style="font-size: 11pt; line-height: 20.7px; font-family: Arial, 'Arial_EmbeddedFont', 'Arial_MSFontService', sans-serif;" xml:lang="EN-US" data-contrast="auto"><span class="NormalTextRun SCXW60355319 BCX2">subtypes of FAP</span><span class="NormalTextRun SCXW60355319 BCX2">.</span></span></span></p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Brendan Anderson, Tina Zhang, MD, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27960Spatially Anchored Molecular Neighborhoods in Lupus Nephritis 2023-12-20T17:33:51-05:00Maansi AsthanaRicardo Melo FerreiraDebora L. GischYing-Hua ChengMichael T. Eadon<div class="page" title="Page 1"> <div class="layoutArea"> <div class="column"> <p><span style="font-size: 11.000000pt; font-family: 'Arial'; font-weight: bold;">Background: </span></p> <p><span style="font-size: 11.000000pt; font-family: 'ArialMT';">Lupus nephritis (LN) affects 1 in 3 individuals with systemic lupus erythematosus. Suboptimal treatment precipitates irreversible kidney damage, leading to end stage renal disease. Kidney damage in lupus is characterized by immune cells injuring epithelial, endothelial, and stromal cells. We characterized molecular neighborhoods composed of immune cells interacting with resident cells of the kidney through spatial transcriptomics (ST). </span></p> <p><span style="font-size: 11.000000pt; font-family: 'Arial'; font-weight: bold;">Methods: </span></p> <p><span style="font-size: 11.000000pt; font-family: 'ArialMT';">Visium ST experiments were conducted in 8 healthy controls (233 glomeruli) and 3 LN samples (48 glomeruli). Cell type labels from the Kidney Precision Medicine Project single cell RNA-seq atlas were transferred to deconvolute ST spots into specific cell types. Using histology and </span><span style="font-size: 11.000000pt; font-family: 'Arial'; font-style: italic;">NPHS2 </span><span style="font-size: 11.000000pt; font-family: 'ArialMT';">expression, glomeruli were selected as functional tissue units. Data were normalized, dimensionally reduced, and clustered with Seurat v4. Spatially anchored gene signatures of LN were identified. Glomeruli were re-clustered according to cell composition, to identify associated neighborhoods by fisher’s exact test. We characterized the cell composition, differentially expressed genes (DEGs), and pathways of relevant neighborhoods. </span></p> <p><span style="font-size: 11.000000pt; font-family: 'Arial'; font-weight: bold;">Results: </span></p> <p><span style="font-size: 11.000000pt; font-family: 'ArialMT';">Between LN and control glomeruli, we identified </span><span style="font-size: 11.000000pt; font-family: 'Arial'; font-style: italic;">HSPA8, PLEK, COL1A2 </span><span style="font-size: 11.000000pt; font-family: 'ArialMT';">DEGs, associated with hypoxia, fibrosis, and immune response. We identified glomerular neighborhoods consistent with immune complex deposition, endothelial dysfunction (e.g. wire loop lesions), and mesangial cell expansion enriched in LN (p<0.05). Immune complex-mediated injury neighborhoods were characterized by interferon signaling, endothelial cell migration, and vascular genesis, consistent with DEGs </span><span style="font-size: 11.000000pt; font-family: 'Arial'; font-style: italic;">BST2, CXCL12, </span><span style="font-size: 11.000000pt; font-family: 'ArialMT';">and </span><span style="font-size: 11.000000pt; font-family: 'Arial'; font-style: italic;">ENG</span><span style="font-size: 11.000000pt; font-family: 'ArialMT';">. Endothelial dysfunction neighborhoods present cellular adhesion, immune cell signaling, and hypoxic pathways. DEGs included </span><span style="font-size: 11.000000pt; font-family: 'Arial'; font-style: italic;">ITGB2, HLA-DPB1, </span><span style="font-size: 11.000000pt; font-family: 'ArialMT';">and </span><span style="font-size: 11.000000pt; font-family: 'Arial'; font-style: italic;">EGR1. </span><span style="font-size: 11.000000pt; font-family: 'ArialMT';">Pathways enriched in mesangial expansion neighborhoods included matrix adhesion, podocyte development, and ERK1 and ERK2 cascade, aligned with </span><span style="font-size: 11.000000pt; font-family: 'Arial'; font-style: italic;">ITGB3, NPHS1, </span><span style="font-size: 11.000000pt; font-family: 'ArialMT';">and </span><span style="font-size: 11.000000pt; font-family: 'Arial'; font-style: italic;">APOE </span><span style="font-size: 11.000000pt; font-family: 'ArialMT';">DEGs. </span></p> <p><span style="font-size: 11.000000pt; font-family: 'Arial'; font-weight: bold;">Conclusion/ Clinical Impact and Implications: </span></p> <p><span style="font-size: 11.000000pt; font-family: 'ArialMT';">Neighborhood characterization provides insight into cell-cell interactions that drive kidney disease progression. Future directions will change how kidney biopsy specimens drive treatment by delineating specific cell-cell interactions, linking molecular and histopathological signatures, and defining genes associated with therapeutic resistance. </span></p> </div> </div> </div>2024-01-11T00:00:00-05:00Copyright (c) 2023 Maansi Asthana, Ricardo Melo Ferreira, Debora L. Gisch, Ying-Hua Cheng, Michael T. Eadonhttps://journals.iupui.edu/index.php/IMPRS/article/view/27961Effects of Social Determinants of Health on Clinical Outcomes in Pediatric Cystic Fibrosis Patients 2023-12-20T17:43:07-05:00Jinan AyubMary de LaosaSarah BilinskiJames ChmielDon B. Sanders<p><strong><span data-contrast="auto">Background and Objective:</span></strong><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p> <p><span data-contrast="auto">Advances in the treatment of cystic fibrosis (CF) with cystic fibrosis transmembrane regulator modulators have improved morbidity and mortality, however, clinical outcomes vary among genetically similar patients due to contributions of social determinants of health (SDOH). Pancreatic insufficiency, CF-related diabetes (CFRD), </span><em><span data-contrast="auto">Pseudomonas </span></em><span data-contrast="auto">infections, and lower BMI increase risk of severe lung disease, measured by forced expiratory volume in 1 second (FEV1). This project aims to identify socially vulnerable patients and evaluate the impact of SDOH on clinical outcomes.</span><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p> <p><strong><span data-contrast="auto">Methods:</span></strong><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p> <p><span data-contrast="auto">From January to July 2023, SDOH screeners were distributed to families of children with CF at Riley Hospital for Children, documenting transportation, housing, food insecurity, insurance, and medication costs. Clinical outcomes for each patient including FEV1% predicted, BMI/WFL percentile, CFRD, hospitalizations, respiratory infections with </span><em><span data-contrast="auto">Pseudomonas aeruginosa</span></em><span data-contrast="auto">, and pancreatic insufficiency within the past 12 months were recorded. Patients were categorized by SDOH vulnerability, and associations with poor clinical outcomes were analyzed using the Chi-squared test of independence.</span><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p> <p><strong><span data-contrast="auto">Results:</span></strong><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p> <p><span data-contrast="auto">A total of 193 screeners were analyzed: males represented 52.6% of the cohort, 2.60% identified as non-white race, and 3.65% reported Hispanic ethnicity. Overall, 51.8% screened positive for at least one SDOH (SDOH+) and 48.1% screened negative (SDOH-). The average FEV1% predicted decline among SDOH+ patients was 5.79% and 3.51% among SDOH- patients. SDOH+ patients were more likely to have at least a 5% decline in FEV1% predicted (p=0.037) and to be hospitalized due to exacerbations of CF lung disease at least once in the past 12 months (p=0.030). Although low BMI percentile, </span><em><span data-contrast="auto">Pseudomonas</span></em><span data-contrast="auto"> infection, and CFRD were not significantly associated with SDOH, socially vulnerable patients demonstrated higher rates of these clinical outcomes.</span><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p> <p><strong><span data-contrast="auto">Conclusion and Clinical Implications:</span></strong><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p> <p><span data-contrast="auto">SDOH impact CF clinical outcomes. Screeners are effective in identifying socially vulnerable patients and serve as the first step in addressing unmet social needs.</span><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Jinan Ayub, Mary de Laosa, Sarah Bilinski, James Chmiel, Don B. Sandershttps://journals.iupui.edu/index.php/IMPRS/article/view/27962Decoding the Link Between XPC and Lung Cancer Susceptibility: A Study of Cigarette Smoke-Induced DNA Damage in the Setting of XPC Deficiency2023-12-21T17:12:18-05:00Marie Nour KaramHuaxin ZhouNawar Al NasrallahCatherine Sears, MD<p><strong>Background/Objective:</strong></p> <p>Despite the known mutagenicity of cigarette smoke, only 10-15% of smokers will develop lung cancer in their lifetimes. What determines a smoker’s susceptibility to lung cancer is poorly understood. We identify the nucleotide excision repair (NER) protein Xeroderma pigmentosum Complementation Group C (XPC) as a tumor suppressor that may contribute to lung<br>tumorigenesis when mutated and combined with cigarette smoke. Micronuclei, which are chromosome fragments and/or lagging chromosomes separated from the main nucleus, occur in many cancers, and indicate genomic instability. We hypothesize that cigarette smoke and XPC knockdown will cause genomic instability that will activate the DNA Damage Response (DDR) and increase the frequency of micronuclei and nuclear aberrancies.</p> <p><strong>Methods:</strong></p> <p>A human bronchial epithelial cell line (Beas-2B), and two lung adenocarcinoma cell lines (H1299 and A549) with stable XPC lentiviral knock-down (shXPC) or control shRNA (shCtrl) were treated with cigarette smoke extract (CSE) or air control (AC). DNA Damage Response (DDR) proteins were analyzed via immunoblot (Western). Micronuclei and nuclear aberrancies were quantified through cytokinesis-block micronucleus assay (CBMT) using immunofluorescence microscopy (DAPI).</p> <p><strong>Results:</strong></p> <p>Both CSE and XPC knockdown independently amplify expression of phospho-ATM (pATM), a DDR protein, in H1299 cells. Nuclear aberrancies increased significantly (p<0.05) with CSE in all three cell lines. Micronucleus frequency increased significantly with CSE in H1299 and Beas-2B cells (p<0.05) and with XPC knockdown in Beas-2B cells compared to shCtrl (p<0.001).</p> <p><strong>Scientific Impact and Implications:</strong></p> <p>We identified a previously uncharacterized role of XPC deficiency in augmenting cigarette smoke induced chromosomal breaks manifesting as micronuclei, particularly in non-cancerous Beas-2B cells. These findings offer insight into tumorigenesis in cigarette smoking and shed light on mechanisms of continued DNA damage in cancer cells. Future research should clarify the mechanisms of micronucleus formation in human translational specimens and pinpoint additional functions of XPC beyond NER, including in replication repair.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Marie Nour Karam, Huaxin Zhou, Nawar Al Nasrallah, Catherine Sears, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27965Comparison of Transfer Patterns by Emergency Medical Services in Trauma Patients in a Major U.S. City2023-12-30T13:17:40-05:00Fezaan KaziAli SualehJeff GuoMuqsit BuchhJamie Bradbury, MD<p><strong>Background:</strong><br>Trauma patients are often unable to communicate a preferred destination hospital to EMS due to their injuries and potentially decreased level of consciousness. The destination hospital is thus determined by the EMS team transporting the patient. This study focuses on trauma admissions between Eskenazi and IUH Methodist Hospitals in downtown Indianapolis, both of which are Level 1 trauma centers within one mile of each other. We are interested in identifying differentiating factors between patients that are admitted at these two hospitals, focusing on the injury type as well as the demographic information for each patient, to determine if there are differential transport patterns.</p> <p><strong>Methods:</strong><br>We performed a retrospective analysis of patient charts and transport documentation to determine basic demographic and admission data for each patient. We especially took note of the location of EMS pickup, the facility the patient was taken to, and the stated reasons for taking the patient to that specific facility. A simple Google Maps search allowed us to determine if the patient was taken to the facility closest to them, or not.</p> <p><strong>Results:</strong><br>We found that among the included patients that were not taken to the nearest Level 1 trauma center, a significant majority were taken to Eskenazi rather than Methodist. Among these patients, a majority were minorities, in contrast with demographic makeup of the patients that were admitted to the closest trauma center.</p> <p>Conclusion:<br>This study highlights how complex EMS transfer patterns are based upon diversion, traffic, individual driver preference, and other factors. There is a significant difference in transport patterns between the two hospitals that correlates with a difference in patient demographics.</p> <p><strong>Policy Implications:</strong><br>This data indicates a need to monitor these numbers closely going forward, paying special attention to all possible reasons that could impact to which facility a patient is admitted.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Fezaan Kazi, Ali Sualeh, Jeff Guo, Muqsit Buchh, Jamie Bradbury, MDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27966Celiac Disease in Medical Curriculum2023-12-30T13:31:49-05:00Elizabeth KernsPolly R. Husmann, PhD<p>Introduction: Celiac disease is a common autoimmune illness precipitated by the ingestion of gluten, a protein contained in grains (e.g., wheat, barley, and rye). Celiac disease can present with a wide variety of manifestations across nearly any body system, but most individuals with celiac disease present with subclinical symptoms. Despite relatively inexpensive testing and an effective treatment (i.e., a gluten free diet), most individuals with celiac disease remain undiagnosed, leading to significant disease burden. Research suggests that physicians have poor knowledge of celiac disease, likely contributing to the high rates of missed diagnoses. This study sought to assess the information encountered by students in pre-clinical medical education regarding celiac disease.</p> <p>Methods: Information was drawn from recent literature to create a rubric to evaluate the presentation of celiac disease in curricular and educational resources for pre-clinical medical students. Categories evaluated included prevalence, morbidity/mortality, manifestations, comorbidities, and testing recommendations. This rubric was used to assess the curriculum from a large US medical school and <em>First Aid for the USMLE Step 1</em>, a popular commercial resource used by medical students.</p> <p>Results: The medical school curriculum scored higher overall than <em>First Aid</em> (31/48 and 12/48, respectively). The curriculum also scored higher in all categories except morbidity/mortality. The curriculum showed deficits predominantly in morbidity/mortality and testing recommendations. <em>First Aid</em> showed deficits in all categories.</p> <p>Discussion: Results showed that the medical school curriculum provided more complete information about several aspects of celiac disease. <em>First Aid</em> did not thoroughly address any of the categories evaluated with the rubric. While <em>First Aid</em> may be an effective consolidation of Step 1 material, it seems likely that it is focused on “teaching to the test” rather than providing thorough medical education for future physicians. The medical curriculum is a more complete resource for students to learn about celiac disease.</p>2024-01-11T00:00:00-05:00Copyright (c) 2023 Elizabeth Kerns, Polly R. Husmann, PhDhttps://journals.iupui.edu/index.php/IMPRS/article/view/27967Diffuse Midline H3 K27-Altered Gliomas in the Spinal Cord: A Systematic Review2023-12-30T13:37:22-05:00Mohammad Faizan KhanMustafa MohamedJennifer Manyu WongBradley Estes Christian OgasawaraGiuseppe E. UmanaPaolo PalmiscianoGina Watanabe<p><strong>Background:</strong> Gliomas account for 80-90% of all intramedullary spinal cord tumors (IMSCTs). Though rare compared to brain tumors, spinal cord gliomas can cause significant morbidity and mortality. Diffuse midline gliomas (DMGs) with H3 K27M-mutation, first introduced in the 2016 WHO classification, are high-grade tumors with aggressive behavior and poor prognosis. The 2021 updated WHO classification renamed them "diffuse midline glioma, H3 K27-altered" to include other molecular changes. Limited single-institution data on spinal cord DMGs (DMGSCs) hinder comprehensive understanding and optimal treatment protocols. In this review, we summarize clinical and molecular features, management strategies, and survival impact in patients with DMG-SCs.</p> <p><strong>Project Methods:</strong> A systematic review was performed following the (PRISMA) guidelines. PubMed, Ovid EMBASE, Scopus, and Web of Science were searched. Clinical characteristics, treatment protocols, and outcomes were analyzed.</p> <p><strong>Results:</strong> A total of 26 studies with 259 patients were included. Most patients were male (63%), diagnosed at a mean age of 32 years (range, 4-72), and tumors were predominately located in the cervical (32%) or thoracic (43%) regions of the spinal cord. Primary management included surgical resection (97%), radiotherapy (78%), and chemotherapy (62%). Most common combination of treatment included surgical resection, radiotherapy, and chemotherapy (47%). The mean overall and progression free survival were 25 (range, 0.1-48) and 14 (range, 0.1-25) months, respectively. Gene alterations included p53 mutation (61%), loss of ATRX (46%), Olig- 2 positive (100%), and GFAP positive (80%). The mean Ki-67/MIB-1 was 23% (12-40%).</p> <p><strong>Conclusion/Impact:</strong> DMG-SCs affect mostly the adult population and appear to resemble adult DMGs in terms of molecular features, management, and prognosis.</p>2024-02-14T00:00:00-05:00Copyright (c) 2023 Mohammad Faizan Khan, Jennifer Manyu Wong, Bradley Estes , Christian Ogasawara, Giuseppe E. Uman, Paolo Palmisciano, Gina Watanabehttps://journals.iupui.edu/index.php/IMPRS/article/view/27974Importance of Per2 in Cardiac Mitochondrial Function during Stress2024-01-02T15:17:17-05:00Meghana BhaskaraOlufisayo AnjorinArris YonilesJean LiuMeijing Wang<p><strong><span data-contrast="auto">Background and Hypothesis:</span></strong> <span data-contrast="none">Ischemic </span><span data-contrast="auto">heart disease is the worldwide leading cause of death. Cardiac cellular damage from ischemia is mainly inflicted in the form of mitochondrial dysfunction by inflammatory cytokines and reactive oxidative species (ROS). Mitochondria are critical for metabolic function to maintain cardiac activity. Interventions against inflammatory cytokines and ROS are therefore cardioprotective during ischemic damage. Period Circadian Regulator 2 (Per2) is a circadian rhythm protein involved in metabolic regulation as a time-responsive gene in cardiomyocytes during ischemic damage. Overexpression of Per2 has been shown to decrease infarct size following myocardial infarction.</span> <span data-contrast="auto">In this study, we hypothesize that Per2 protein plays a regulatory role in the mitochondrial response to inflammatory cytokine TNFα and oxidative stressor H</span><span data-contrast="auto">2</span><span data-contrast="auto">O</span><span data-contrast="auto">2 </span><span data-contrast="auto">in human cardiomyocytes.</span><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p> <p><strong><span data-contrast="auto">Project Methods:</span></strong><span data-contrast="auto"> AC16 Human Cardiomyocytes (HCM) transfected with Per2 or control siRNA were subjected to stress treatment of </span><span data-contrast="none">100ng/mL </span><span data-contrast="auto">TNFa or 100μM H</span><span data-contrast="auto">2</span><span data-contrast="auto">O</span><span data-contrast="auto">2</span><span data-contrast="auto">. RT-PCR and Western blot were used to detect Per2 expression. After two hours of treatment, mitochondrial membrane potential (</span>[Equation]<span data-contrast="auto">M</span><span data-contrast="auto">) was detected using JC1 fluorescence probe and mitochondrial respiration capacity was evaluated via Seahorse Mito Stress Test. After four hours of treatment, cell death was measured using Annexin V and propidium iodide (PI) apoptosis kit via flow cytometry. </span><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p> <p><strong><span data-contrast="auto">Results:</span></strong><span data-contrast="auto"> Per2 siRNA significantly reduced Per2 mRNA and protein levels in HCM. Increased cell death and decreased </span>[Equation]<span data-contrast="auto">M</span><span data-contrast="auto"> were observed in HCM treated with TNFa or H</span><span data-contrast="auto">2</span><span data-contrast="auto">O</span><span data-contrast="auto">2</span><span data-contrast="auto">. Knockdown of Per2 potentiated TNFa-induced cell death, TNFa- or H</span><span data-contrast="auto">2</span><span data-contrast="auto">O</span><span data-contrast="auto">2 </span><span data-contrast="auto">-disrupted </span>[Equation]<span data-contrast="auto">M</span><span data-contrast="auto">, and TNFa- or H</span><span data-contrast="auto">2</span><span data-contrast="auto">O</span><span data-contrast="auto">2</span><span data-contrast="auto">- impaired mitochondrial maximal respiration. </span><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p> <p><strong><span data-contrast="auto">Conclusion and Potential Impact:</span></strong><span data-contrast="auto"> Per2 knockdown increases apoptotic susceptibility and mitochondrial dysfunction in human cardiomyocytes exposed to TNFa or H</span><span data-contrast="auto">2</span><span data-contrast="auto">O</span><span data-contrast="auto">2</span><span data-contrast="auto">. Delivery of Per2 may serve as a promising therapeutic strategy to protect cardiomyocyte mitochondrial function during periods of stress, such as myocardial infarction, organ transplantation, and cardiac surgery. </span><span data-ccp-props="{"201341983":0,"335559740":276}"> </span></p>2024-01-11T00:00:00-05:00Copyright (c) 2024 Meghana Bhaskara, Olufisayo Anjorin, Arris Yoniles, Jean Liu, Meijing Wanghttps://journals.iupui.edu/index.php/IMPRS/article/view/28050Extracranial Meningioma Metastasis: A Systematic Review of Clinical Characteristics, Management Strategies, and Outcomes2024-02-13T13:47:21-05:00Mohammad Faizan KhanMustafa MohamedKurtis YoungErin RauberChristian OgasawaraGiuseppe E. UmanaPaolo PalmiscianoGina Watanabe<p><strong>Background:</strong> Meningioma is the most common type of intracranial neoplasm, accounting for approximately 40% of all primary brain tumors. Although these tumors are usually benign and slow-growing, extracranial metastasis can occur in less than 1% of cases. Due to the rarity, diagnosis can pose a challenge. In this systematic review, we summarize and analyze patient demographics, clinical characteristics, management strategies, and outcomes of patients with extracranial meningioma metastasis.</p> <p><strong>Project Methods: </strong>A systematic review was performed following the (PRISMA) guidelines. PubMed, Ovid EMBASE, Cochrane, Scopus, and Web of Science databases were searched. Clinical characteristics, management, and outcomes were analyzed.</p> <p><strong>Results:</strong> A total of 127 studies with 164 patients were included. There were 51% males and mean age of primary tumor diagnosis was 48 years (range, 8-91). Primary tumors were mostly located on the convexity of the brain (52%) and WHO grade 1 (38%) or grade 2 (37%). Histological findings were predominantly atypical (37%). Mean number of intracranial recurrences was 2 (range, 0-7) and occurred in 81% of cases. Average time between primary tumor and the first extracranial metastasis was 103 months (range, 2-450). The top three most common locations of metastases were the lungs (39%), spine (15%), and liver (12%). Most often, there was no change in grade (68%) from the primary tumor to the first metastasis. Gross total resection of the primary tumor was achieved in 76% of cases. Mean survival from primary diagnosis and survival from first metastasis was 118 and 31 months, respectively.</p> <p><strong>Conclusion/Impact:</strong> Mechanisms by which extracranial meningioma metastasis occur are still unclear, though do not appear to involve evolution into a more aggressive histologic type in most cases. In a patient with a history of intracranial meningioma recurrence and symptoms of lung, spine, or liver, dysfunction, extracranial meningioma metastasis should be considered within the differential.</p>2024-02-13T00:00:00-05:00Copyright (c) 2024