Session A: 9AM – 10:30AM
Health and Medicine. Session A – Poster Presentations, Ballroom, Union
SESSION A (9:00-10:30AM)
Location: Ballroom, A. Ray Olpin University Union
Isothiocyanates as NRF2 upregulators in the prevention of neural tube defects in chick embryos
Claire Bruno, Brigham Young University
Cailey Winn, Brigham Young University
Katrina Lantz, Brigham Young University
Faculty Mentor: Michael Stark, Brigham Young University
SESSION A (9:00-10:30AM)
POSTER A66
Neural Tube Defects (NTDs)-anencephaly and spina bifida-remain a persistent problem across the globe, despite folic acid (FA) supplementation in many nations. NTDs rates in areas with insufficient FA supplementation are higher. In India the prevalence of NTDs is estimated at 4.5 per 1000 live births. In some rural areas, the prevalence peaked at 18 NTDs per 1000 live births. Recent studies suggest a role for oxidative stress in the pathogenesis of NTDs. Isopropyl isothiocyanate (IPI), active ingredient in the leaves/seeds of the Moringa tree (Moringa oleifera) is a known antidiabetic compound countering inflammation, an oxidative stress condition. It is known to activate NRF2 cofactor, an important regulator for oxidative stress. We hypothesize IPI will promote NRF2 activity in chick embryos and reduce chemically-induced oxidative stress to prevent the formation of NTDs. Because Moringa thrives along the equator where medical and nutritional access are historically poor, if shown to be effective, it may increase access to protection from developmental insults in places without FA supplementation programs. Using a cell viability assay in cultured cells, the optimum concentration of IPI was determined. Chick embryos were pretreated or cotreated with IPI 6 hours before plating on chemicals known to induce NTDs-ceramide or valproic acid (VPA)-and left for 24 hours. Embryos were then collected, scored for frequency of NTDs, and measured against control embryos pretreated with increasing dosage of FA, which is known to rescue NTDs, and control embryos receiving no pretreatment. The redox state of the tissue was evaluated. NRF2 target gene expression analysis by quantitative PCR is planned. This project may advance the developmental biology field, ascertaining whether IPI effectively regulates NRF2 expression and oxidative stress, potentially preventing the pathogenesis of NTDs. Next steps include confirming results in the mammalian model to establish relevance to humans.
Spinning Disk as a Novel Method for Isolation of Plasma Prior to Cell-free Ribonucleic Acid (cfRNA) Extraction and Utilization
Mae-Lynn Hutchinson, Brigham Young University
Faculty Mentor: Bill Pitt, Brigham Young University
SESSION A (9:00-10:30AM)
POSTER A67
The utilization of cell-free ribonucleic acids (cfRNA), such as found in a liquid biopsy, has revolutionized the early detection and monitoring of some health conditions. Such conditions include pregnancy complications, viral infections, and cancer. cfRNA is typically isolated through a rapid centrifugation procedure; however, the use of an inexpensive spinning disk has been considered in some locations and applications. Briefly, this approach involves applying a centrifugal field to a hollow spinning disk to remove cellular material, with RNA remaining, from the blood sample in ~2 minutes.To examine the effectiveness of these two methods, blood was collected from healthy donors into pairs of Streck RNA Complete BCT tubes. Sample hematocrit was measured and samples were diluted with phosphate buffered saline (PBS) to a consistent hematocrit of 32. From each pair of samples, one control sample underwent the standard centrifugation process, while the other sample underwent the spinning disk procedure to collect plasma. Plasma hemolysis was evaluated using spectrophotometry according to the Harboe method with the Allen correction prior to cfRNA isolation. Following cfRNA isolation, qRT-PCR of the GAPDH and beta-actin transcripts was performed to evaluate quality and quantity of the cfRNA recovered by each method. We found that cfRNA yield from the centrifugation and the spinning disk methods did not differ significantly (p = 0.077), though there was significantly more hemolysis in the plasma from the spinning disk method (p = 0.004). Our findings suggest that the spinning disk could expand possibilities for rapid, effective, high-quality treatment and monitoring of patients living in areas where a full-size high speed centrifuge is not accessible since the disk is much smaller and cheaper than other platforms.
Role of LRP1ab Receptor In Microglia Inflammatory and Phagocytosis Response
Aasutosh Acharya, University of Utah
Faculty Mentor: Peter Hitchcock, Other: High School
SESSION A (9:00-10:30AM)
POSTER A68
Unlike mammals, zebrafish have the ability to regenerate their central nervous system. We study the regeneration process that takes place in zebrafish retinas after their photoreceptors have been damaged. This regeneration requires an inflammatory response, mediated cells called microglia. Midkine-a is a cytokine required for microglia to phagocytose dying photoreceptors, a key step in regulating inflammation. In the absence of midkine-a, microglial phagocytosis fails. This project tested the hypothesis that the putative midkine-a and microglia-specific receptor, Lrp1ab, is also required for the microglial phagocytosis of dying photoreceptors. After creating a photoreceptor lesion in a Lrp1ab mutant (-/-) fish, we investigate how the microglia phagocytosis process is affected without the presence of the Lrp1ab receptor by staining for microglia. To study the effect even further, we go beyond just microglia and also stain for proliferating cells. The results of the staining revealed the nature of microglia and proliferation cells, however, some unexpected changes to the morphology of the microglia were also observed.
Establishing Baseline Numbers for Isometric Back Muscle Endurance in the Dance Population
Megan Brooks, University of Utah
Faculty Mentor: Justin Rigby, University of Utah
SESSION A (9:00-10:30AM)
POSTER 69
Context: Medical providers can better recognize and treat injuries caused by deviation, such as back pain when normative and baseline values are known. Dancers are often a forgotten population. Researchers have yet to determine dancers’ normative back and core muscle endurance values. Study Purpose: This study aims to 1) fill a gap and collect normative and baseline values after four trunk muscle endurance tests and 2) determine if the normative values differ between dancers with a history of back pain. Hypothesis: I hypothesized that the dance population’s normative values for trunk muscle endurance tests would differ from those for other athletes. I also hypothesized that dancers with back pain would have lower endurance times. Methods: We tested university dance majoring students using McGill’s Torso Muscular Endurance Test. We applied McGill’s test according to standard procedures. We measured the amount of time, in seconds, dancers could hold four different positions (trunk extension, trunk flexion, and right and left side plank). We used descriptive statistics to create normative values for our dance population and compared the results to existing other athletic populations’ research literature. Results: Dancers could hold the back extension position the longest (188.2 ± 64.7 s), followed by trunk flexion (124.8 ± 79.2 s), right side plank (82.9 ± 31.9 s), and left side plank (80.2 ± 20.1 s). When the data was separated into dancers with a history of lower back pain and dancers with no history, those with a history of pain had slightly lower normative averages. Conclusion: Dancers have higher extension endurance ability than other populations. Clinicians should consider normative trunk endurance values when treating dancers. They may appear to have normal levels of extension strength compared to other athletic populations but have decreased ability compared to dancer norms. Understanding dancers’ trunk muscular abilities is vital to treating them effectively.
Lower Limb Kinematics and Kinetics Associated with Walking in Older Adults with End-Stage Hip Osteoarthritis
Hunter Carlson, University of Utah
Faculty Mentor: Jesse Christensen, University of Utah
SESSION A (9:00-10:30AM)
POSTER A70
Osteoarthritis is the most common joint disease in the world. [12] Its prevalence in the hip joint is observed to have dramatic adverse effects on the quality of life of aging adults and can contribute to more significant health issues. [1] Hip osteoarthritis (HOA) reflects a breakdown in hip mechanics, muscle strength, and decreased biomechanics. [4, 8] The purpose of this study is to compare the relationship between deficits in hip mechanics of the frontal (primary) and sagittal (secondary) planes onto physical function, using validated physical performance and muscle strength metrics in adults with HOA. We hypothesized that more significant deficits in the involved limb’s hip mechanics (angle, moment, power) would be associated with poorer Two-Minute Walk Test and 30-Second Sit-to-Stand Test performance. We also hypothesized that more significant deficits in hip mechanics would be associated with greater hip abduction, knee extension, and knee flexion weakness of the involved limb. The data collection and processing have been assisted by Chelsea Wilbur and Bennet Browning. This study is still in progress; results and discussion will be added upon completion.
Effects of Increasing Sleep Duration on CRP Levels, Insulin Sensitivity, and Blood Pressure in Adults with Habitual Insufficient Sleep
Alisha Chong, University of Utah
Faculty Mentor: Christopher Depner, University of Utah
SESSION A (9:00-10:30AM)
POSTER A71
Insufficient sleep is highly prevalent in the adult population and often goes unaddressed during patient visits in health clinics. Previous studies demonstrate that receiving insufficient sleep is linked to an increased risk of other health issues like type 2 diabetes and heart disease. However, the relationships and mechanisms underlying how sleep affects these health issues is not well known. Thus, the current study aims to investigate the impact of insufficient sleep on C-reactive protein (CRP) levels, insulin sensitivity, and blood pressure. CRP is an inflammatory marker which has been linked to a greater risk of cardiovascular events, and prior research has found conflicting information on whether insufficient sleep significantly affects CRP levels. Additionally, reduced insulin sensitivity is associated with type 2 diabetes, and both type 2 diabetes and high blood pressure may increase cardiovascular disease risk. Understanding how insufficient sleep affects insulin sensitivity as well as blood pressure and CRP levels may provide insight into the means by which insufficient sleep increases type 2 diabetes and cardiovascular disease risk. Data collection is ongoing with 12 participants completing the study to date. The study protocol consists of measuring CRP levels, insulin sensitivity, and blood pressure of healthy individuals aged 18-35 who chronically receive insufficient sleep (<6.5h). After baseline assessments, participants complete a 4-week intervention aiming to increase their sleep duration to the recommended 7 hours of sleep per night. Sleep duration throughout the study is monitored using an Actiwatch and sleep logs. Of the 12 participants who have completed the study, sleep duration was 5.7±0.2 (±SEM) hours at baseline and significantly increased (p<0.001) by ~38.4±5.4 minutes during sleep extension. Further analyses of CRP, blood pressure, and insulin sensitivity data at baseline and at intervention will provide insight into how or whether increasing sleep duration can mitigate risk of diabetes and cardiovascular disease. The current hypothesis is that increasing sleep duration of people chronically receiving <6.5h of sleep per night will lower plasma CRP levels, decrease blood pressure, and increase insulin sensitivity. A better understanding of how insufficient sleep increases risk of cardiometabolic disease could help inform interventions designed to prevent chronic diseases like diabetes and cardiovascular disease.
Effects of Increasing Sleep Duration and Sleep Efficiency
Hailee Fell, University of Utah
Faculty Mentor: Christopher Depner, University of Utah
SESSION A (9:00-10:30AM)
POSTER A72
Introduction: Short sleep duration and reduced sleep efficiency are two dimensions of sleep health that are associated with adverse effects on overall health including mortality, coronary heart disease, hypertension, and diabetes. However, we have limited knowledge on the efficacy of interventions (sleep extension) to improve sleep and if improving sleep can mitigate these adverse health outcomes. In this research, we will define the effects of a sleep extension intervention on multiple dimensions of sleep health in people who report habitual short sleep duration. Methods: Data collection is still ongoing. To date, 12 healthy participants (8 male, 4 female), aged 20.7± 2.5 y (mean+SD), BMI 21.8 ± 2.3 kg/m2 with reported habitual short sleep duration (<6.5h per night) have completed the study. For the study protocol, participants complete 2 weeks of baseline at-home monitoring followed by 4 weeks of sleep extension, where participants are asked to extend their time in bed to 8 hours per night. Sleep is measured by self-report sleep diaries and wrist-actigraphy. The dimensions of sleep health measured are sleep duration, timing (midpoint of sleep), efficiency (percent of sleep time out of total time in bed), and regularity (standard deviation of sleep duration during baseline and sleep extension segments). Results: Sleep duration was 5.7±0.2 (mean±SEM) hours at baseline and significantly increased (p<0.001) by 38.4±5.4 (mean±SEM) minutes during sleep extension. Sleep midpoint was 4:58 am±17 minutes (mean±SEM) at baseline and shifted significantly earlier (p<0.05) to 4:38 am±7 minutes (mean±SEM) during sleep extension. No statistically significant differences were detected between baseline and sleep extension for sleep regularity and efficiency. Conclusion: Short average sleep duration and reduced sleep efficiency are linked to a range of health problems such as mortality, coronary heart disease, hypertension, and diabetes. Data show our sleep extension intervention where participants were asked to extend their nightly time in bed to 8 hours has the capacity to increase sleep duration and shift the timing of sleep earlier in the night. These changes are considered positive changes to sleep and future studies are needed to understand if these changes can lead to improved health outcomes. Our findings also show sleep extension did not influence sleep regularity or efficiency, and thus different interventions are likely needed that target these dimensions of sleep health. Support: NIH-UL1TR002538, NIH-K01HL145099, Colorado Clinical Translational Science Institute Pilot (CO-J-20-119), University of Utah Seed Grant-10060570, Margolis Foundation, LEAP Program.
The Effect of mild Traumatic Brain Injuries on Turning Smoothness
Cameron Jensen, University of Utah
Faculty Mentor: Peter Fino, University of Utah
SESSION A (9:00-10:30AM)
POSTER A73
Purpose: Mild traumatic brain injuries (mTBIs; i.e. concussions) can impair a person’s motor function, and lead to worse static balance than healthy individuals (Haran, 2016), and emerging research suggests that more dynamic tasks, such as turning, are particularly susceptible to the effects of mTBI (Fino, 2016, 2018a). While previous work has focused on speed and balance during turning (Fino, 2016, 2018a), the smoothness of a turn may also be important; the ability to perform pre-planned movements in a smooth, non-jerky manner is an important marker of a neurologically healthy motor control (Hogan, 2009). Smoothness is a relevant and valid way to quantify movement quality in people with impaired functional mobility, such as individuals with an mTBI, and it can be a good indicator of pathology (Beck, 2018; Pinto, 2019). As the effects of mTBI on the smoothness of turning remain unclear, this study sought to examine the acute and longitudinal effects of mTBI on movement smoothness during turning. We hypothesized that those with an mTBI would exhibit less smooth turns, and smoothness would improve as individuals recovered from their mTBI. Methods: As part of a larger IRB-approved protocol, 11 healthy controls and 10 mTBI subjects walked around a turning course for 140 seconds after providing informed written consent. The turning course was made up of turns of varying angles. Participants completed three separate conditions: single-task, dual-task (turning while simultaneously counting down by 3’s), and fast walking. Each subject was tested at an acute time point (within 2 weeks of receiving an mTBI) and then tested again three months later. Kinematic data was recorded from inertial measurement units (IMUs), and smoothness of axial rotation was quantified using log dimensionless jerk from the angular velocity data in the transverse (yaw) plane. Movements with less jerk are described as being smoother. For each of the three conditions, comparisons were made, in the form of t-tests, between the controls’ two visits, between the mTBI subjects’ two visits, and between the controls and mTBI subjects at each visit. Results: During the single task condition, participants with mTBI exhibited less smooth turns at the follow-up visit compared to the acute visit (Acute mean (SD): -30.18 (0.75) a.u.; Follow-up mean (SD): -30.73 (0.88) a.u. ; p=0.004). No other significant results were found during the preliminary analysis. Conclusions : The decreased smoothness over time was the opposite of our hypothesis, but these results may indicate that people with mTBI prioritize smoothness initially to avoid provoking symptoms. Alternatively, smoother turns in those with acute mTBI may be due to slower turning speeds; future work will consider turning speed as a covariate to account for this potential confounding factor.
Identification of 42 Potential Intestinal Oncogenes via a RNAi Screen Using Fruit Flies
Carter Niedert, University of Utah
Faculty Mentor: Bruce Edgar, University of Utah
SESSION A (9:00-10:30AM)
POSTER A74
Colorectal cancer is the third most common cancer in the United States and the second leading cause of cancer related deaths. Cancer deaths occur due to the disruption of normal physiological processes caused by rapid and uncontrolled cell proliferation. Cell proliferation in cells is often triggered through cellular damage sensing pathways. A better understanding of these pathways could lead to cancer treatments that dampen these pathways and control cell proliferation. Cell proliferation occurs rapidly in the gut due to constant exposure to stressors from the external environment. Cells in the gut can sense damage caused by these stressors and trigger renewal of gut epithelial tissues via intestinal stem cell (ISC) proliferation. ISC Proliferation is generally thought to be regulated by the release of specific cytokines from neighboring cells. Some specific genes involved in the release of cytokines that cause ISC proliferation, such as gene p38, have only been recently discovered. There are many genes involved in damage sensing pathways in the intestines that remain unidentified. The aim of this project was to identify which genes in the gut are responsible for sensing damage and activating cell proliferation. This was accomplished by performing RNAi gene knockdown on Drosophila melanogaster, stressing the midgut via bacterial infection by Pseudomonas entomophila (P.e.) to increase cell proliferation, then dissecting and removing the midgut to analyze the effect gene knockdown had on cell proliferation. Of the 192 genes screened, knockdown of 59 genes led to increased cell proliferation and knockdown of 19 other genes led to decreased cell proliferation. Further studies targeting these genes of interest could lead to a deeper understanding of damage-sensing signaling pathways and to novel cancer treatments that can target specific genes.
Role of CD8aa cells in Experimental Autoimmune Encephalomyelitis
Annie Pugmire, University of Utah
Faculty Mentor: Brian Evavold, University of Utah
SESSION A (9:00-10:30AM)
POSTER A75
Multiple sclerosis (MS) is a neurodegenerative disease which causes numbness, paralysis, pain and fatigue as a result of the body’s immune system attacking the central nervous system (CNS). Diagnosis occurs between the ages of 20 and 50 and disproportionately affects women and people of Northern European descent. This disease affects approximately 2.8 million people worldwide, and even with treatment, shortens life expectancy by approximately seven years (Walton et al.). Many risk factors have been identified and immunotherapies developed, but no specific cure or definitive cause has been found. The current immunotherapies used for MS target the entire immune system and can have significant immunocompromising side effects (Rafiee et al).To model MS and investigate the cells contributing to autoimmunity, we use the murine model, Experimental Autoimmune Encephalomyelitis (EAE). Per this model, following delivery of Myelin Oligodendrocyte Glycoprotein (MOG) 35-55 alongside an adjuvant, mice show the same demyelination found in MS and exhibit similar symptoms. In both MS and the EAE model, CD4 T cells have been implicated as major contributors of autoimmune disease. However, both CD8 and CD4 T cells are present in MS lesions (Konjevic et al). In this study, we look specifically at a type of CD8 T cell present in the CNS of mice induced with EAE. This T cell, CD8aa, expresses an alpha homodimer instead of the classical alpha-beta heterodimer present in conventional CD8 T cells. Proposed to have an inhibitory function, these CD8aa cells are only significantly present in sick mice. We show that CD8aa expression correlates with disease severity, that these cells have a central memory phenotype, and that their expression of NK like markers acts to dampen the autoimmune response during EAE. Investigation into these cells could have major implications for future treatment of MS, allowing the targeting of effector CD8 T cells while leaving the CD8aa cells intact.
Understanding the Early Molecular Level Changes Associated with Radiation Treatment – A Preliminary RNA Sequencing Study
David Rou, University of Utah
Faculty Mentor: Sujee Jeyapalina, University of Utah
SESSION A (9:00-10:30AM)
POSTER A76
Affecting one in 8 women, breast cancer is the second most common cancer in women in the United States. In 2019, 42,280 deaths were reported as a result of breast cancer. The standard of care for treatment is surgical tumor excision with sentinel lymph node biopsy and adjuvant radiation therapy. Although this standard procedure significantly improved tumor-free survival rate, 10-12% of patient morbidity is reported due to radiation-induced tissue fibrosis (RIF). To date, very little is known about its etiologies. To bridge this knowledge gap, this study was designed to understand the differences in RNA expression between radiated and non-radiated breast tissues using RNA sequencing techniques and immunohistochemistry (IHC). Using the approved Institutional Review Board protocol (University of Utah: 00047788), those patients who elected to undergo a double mastectomy but only had radiation therapy to the affected single breast were recruited. Post-radiation therapy, tissue samples (skin, fibrous capsule, and muscle) were collected from both breasts, the total RNAs were extracted, and a complete sequencing study was performed. Post-processing, the differentially expressed genes (DEGs) were identified, and their abilities to over and under-translate the corresponding proteins were validated using IHC. The data did confirm the over- and under-translations of respective proteins. This pilot data clearly indicates the utilities of complete RNA sequencing in understanding the mechanisms of RIF.
Examining the Role of Non-Canonical Wnt Signaling in Adrenal Homeostasis and Hyperplasia
Catherine Rousculp, University of Utah
Faculty Mentor: Kaitlin Basham, University of Utah
SESSION A (9:00-10:30AM)
POSTER A77
The Wnt signaling pathway plays an essential role in development and tissue homeostasis and is aberrantly activated in many human cancers(1). There are two main Wnt signaling pathways, the canonical Wnt pathway, involving regulation of B-catenin, and the non-canonical Wnt pathway, which mediates signaling through other effector molecules. While canonical Wnt has been extensively researched, non-canonical Wnt remails relatively unexplored. ZNRF3, an E3 ubiquitin ligase, negatively regulates Wnt signaling and targets Frizzled (FZDs) receptors for degradation. Since FZDs can be in complex with co-receptors that mediate canonical (e.g., LRP5/6) or non-canonical Wnt (e.g., ROR1/ROR2, or RYK), ZNRF3 has the potential to regulate both pathways(2,3). To study ZNRF3 and non-canonical Wnt, we are using the adrenal gland as a model. Located above the kidneys, it produces hormones to regulate stress, metabolism, and homeostasis(4). Wnt signaling is known to be critical for adrenal development and homeostasis(5), and ZNRF3 is frequently inactivated in adrenal cancer(6). Prior work in the lab has revealed that mouse adrenals with Znrf3 conditionally knocked out (cKO) display significant hyperplasia at 6 weeks of age(7). While this phenotype is highly dependent on Wnt ligand availability, it remains unclear if this phenotype requires canonical or non-canonical Wnt, or perhaps both. To examine a potential role of non-canonical Wnt in ZNRF3-dependent signaling, the lab measured expression of non-canonical co-receptors in adrenal glands of Znrf3 cKO mice. This revealed that RYK was more highly expressed as compared to the controls, suggesting it may be a ZNRF3 target and key mediator of non-canonical Wnt. To further examine the role of RYK in normal adrenal biology and in relation to ZNRF3, we generated a Ryk cKO mouse model, where the gene has been selectively inactivated in all adrenal cortex cells using Cre/lox technology, and a double knockout (dKO) model where both Znrf3 and Ryk are simultaneously inactivated. We have found a 35% and 27% reduction in adrenal size in male and female mice, respectively, in the Znrf3;Ryk dKOs as compared to Znrf3 cKOs. Using immunohistochemistry (IHC), we have found that while there is no significant difference in proliferation (p=0.55), there is a significant increase in myeloid cells in the dKO as compared to the Znrf3 cKO (p=0.021). Prior work has shown myeloid cells phagocytose damaged adrenal cortex cells(8), suggesting loss of Ryk may enhance immune-mediated cell clearance. Our next step is to perform RNA sequencing to determine differences in the transcriptome of the control adrenal versus the Ryk cKO, and in the Znrf3 cKO versus the Znrf3;Ryk dKO. Based on the signaling pathways that are changed, we will perform follow-up studies to functionally validate these results. We will also conduct further IHC analyses to investigate other possible explanations for the hyperplastic reduction.
(1) MacDonald, B. T.; Tamai, K.; He, X. Wnt/β-Catenin Signaling: Components, Mechanisms, and Diseases. Developmental Cell 2009, 17 (1), 9-26. https://doi.org/10.1016/j.devcel.2009.06.016.
(2) Fradkin, L. G.; Dura, J.-M.; Noordermeer, J. N. Ryks: New Partners for Wnts in the Developing and Regenerating Nervous System. Trends in Neurosciences 2010, 33 (2), 84-92. https://doi.org/10.1016/j.tins.2009.11.005.
(3) Green, J.; Nusse, R.; van Amerongen, R. The Role of Ryk and Ror Receptor Tyrosine Kinases in Wnt Signal Transduction. Cold Spring Harb Perspect Biol 2014, 6 (2), a009175. https://doi.org/10.1101/cshperspect.a009175.
(4) Adrenal Glands, 2022.
(5) Berthon, A.; Martinez, A.; Bertherat, J.; Val, P. Wnt/β-Catenin Signalling in Adrenal Physiology and Tumour Development. Molecular and Cellular Endocrinology 2012, 351 (1), 87-95. https://doi.org/10.1016/j.mce.2011.09.009.
(6) Hao, H.-X.; Jiang, X.; Cong, F. Control of Wnt Receptor Turnover by R-Spondin-ZNRF3/RNF43 Signaling Module and Its Dysregulation in Cancer. Cancers 2016, 8 (6), 54. https://doi.org/10.3390/cancers8060054.
(7) Basham, K. J.; Rodriguez, S.; Turcu, A. F.; Lerario, A. M.; Logan, C. Y.; Rysztak, M. R.; Gomez-Sanchez, C. E.; Breault, D. T.; Koo, B.-K.; Clevers, H.; Nusse, R.; Val, P.; Hammer, G. D. A ZNRF3-Dependent Wnt/β-Catenin Signaling Gradient Is Required for Adrenal Homeostasis. Genes Dev 2019, 33 (3-4), 209-220. https://doi.org/10.1101/gad.317412.118.
(8) Warde, K. M.; Liu, L.; Smith, L. J.; Lohman, B. K.; Stubben, C. J.; Ekiz, H. A.; Ammer, J. L.; Converso-Baran, K.; Giordano, T. J.; Hammer, G. D.; Basham, K. J. Senescence-Induced Immune Remodeling Facilitates Metastatic Adrenal Cancer in a Sex-Dimorphic Manner; preprint; Cancer Biology, 2022. https://doi.org/10.1101/2022.04.29.488426.
A feasibility trial to determine the effect of mindfulness on weight-loss maintenance
Jackie Smith, University of Utah
Faculty Mentor: Tanya Halliday, University of Utah
SESSION A (9:00-10:30AM)
POSTER A78
PURPOSE: Over 70% of adults in the U.S. have overweight and obesity. Weight loss is often recommended to improve overall health and risk of disease. However, weight regain following intentional weight loss is common, and diminishes initial improvements. Therefore, interventions aimed at attenuating weight regain following weight loss are of crucial importance. Mindfulness-based interventions are a promising and novel approach in mitigating weight re-gain. Therefore, the aim of this study was to investigate the effects of a mindfulness intervention to prevent weight regain in weight-reduced adults. METHODS: Women (age: 40.2 ± 10.8; BMI: 31.6 ± 5.2) who recently achieved a 7% reduction in body mass within the past 2 months were enrolled into an 8-week KORU mindfulness intervention (n=7). The intervention consisted of a weekly 75-minute sessions involving mindfulness-meditation, plus daily meditation homework. At baseline and post-intervention body mass, dietary restraint, disinhibition, and hedonic hunger (via the Three-Factor Eating Inventory); and physical activity (via IPAQ) were evaluated. To compare change in body mass to a standard weight loss maintenance intervention (Diabetes Prevention Program [DPP] Post Core Curriculum), 8-week weight loss data from historic controls matched on age, sex, and BMI (n=5) was utilized. RESULTS: Weight loss was maintained following the 8-week KORU intervention, and was not significantly different from the historical DPP controls (KORU: -0.04 ± 1.2% vs. DPP: 0.09 ± 0.7%). No significant changes were detected in the KORU mindfulness group from pre- to post-intervention for dietary restraint (pre: 11.7 ± 4.1; post: 12.7 ± 4.5; p=0.27), disinhibition (pre: 6.3 ± 4.4; post: 6.6 ± 4.8; p=0.69), or hedonic hunger (pre: 3.7 ± 2.6; 2.9 ± 3.8; p=0.29). Additionally moderate-to-vigorous physical activity (pre: 12114.1 ± 8706.3 METmins/week; post: 7422± 5842.8 METmins/week; p=0.17) and sedentary time (pre: 4274.3 ± 1544.9 min/week; post: 2655.7 ± 1508.8 min/week; p=0.43) were also not changed following the KORU intervention. CONCLUSIONS: Mindfulness-interventions are feasible and an efficacious approach for short-term weight loss-maintenance. Future trials that include matched controls and longer term follow up are needed.
Comparing Contraceptive Use Prior to and After Abortion In Utah- The Role of Rurality In Contraceptive Decision Making
Maegan Thomas, University of Utah
Faculty Mentor: Rebecca Simmons, University of Utah
SESSION A (9:00-10:30AM)
POSTER 79
Introduction/ Objective: Contraceptive options may be limited for people in rural Utah in comparison their urban counterparts. Our objective was to assess contraceptive method use and selection before and after abortion services among rural and urban individuals. Methods: We utilized data from a study assessing contraceptive use prior to and after abortion. This study collected pre-and post-abortion data from participants, including contraceptive methods used prior to pregnancy, and contraceptive methods used at 3-months after their abortion. We conducted multivariable linear and logistic regression models to assess contraceptive use patterns and compare differences in contraceptive use. All analyses were conducted using Stata. Results: A total of 527 were enrolled in the parent study, 49 (9.3%) of whom were from rural areas. Our analyses found that rural people reported using fewer contraceptive methods prior to their abortion than urban individuals (ARR: -0.053; 95% Cl: -0.531- 0.423). The majority of our findings did not reach statistical significance, likely due to the small sample of rural participants. However, our study did identify several points of borderline significance for further investigation. We found that people who reported difficulty in accessing contraceptives were more likely to report using a method they’d previously used before at their 3-month post abortion follow-up (ARR: 0.178; 95% CI: -0.145, 0.502). Among participants, rural people were more likely to report use of the same method pre- and post-abortion (AOR: 1.73; 95% CI: 0.359, 8.337). We also found that rural participants were more likely to report acquiring their birth control online (AOR: 2.7; 95% CI: 0.83, 8.75). Conclusion: Rural and urban participants showed some differences in both the number of methods they’d used prior to their abortion, as well as their ability to access methods pre/post-abortion which supports the need for additional research.
Exploring Novel PI3K-AKT-MTOR Therapy Inhibition as a Treatment for BRAF-Mutant Melanoma
Ashley Thompson, University of Utah
Faculty Mentor: Gennie Parkman, University of Utah
SESSION A (9:00-10:30AM)
POSTER A80
Despite emerging therapies, melanoma progression and metastasis is the leading cause of death for skin cancer patients (Liu, et al. 2014). There is a 15-20% five-year survival rate for Stage IV melanoma, proving the need for new targeted therapies. The phosphatidylinositol-3′-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways play a significant role in cell proliferation. In the MAPK pathway, BRAF is the most commonly mutated proto-oncogene found in melanoma metastases. However, mutation of this gene alone does not lead to melanomagenesis (Parkman, et al. 2021). Melanomagenesis requires further mutational burden within other signaling pathways, such as the PI3K pathway. AKT, a downstream effector of the PI3K pathway, promotes activation of mTORC1, a protein that drives cell proliferation. SGK is highly homologous to AKT, sharing downstream effectors and promoting mTORC1 activation (Sommer, et al. 2013). Therapies targeting BRAF have shown success in inhibiting the MAPK pathway; nevertheless, the PI3K pathway remains active and able to promote cell growth. To combat the activation of the PI3K pathway, therapeutics have been developed to inhibit AKT and PI3K. However, PI3K and AKT-targeted therapeutics have not successfully reduced melanoma metastasis and thus have not been FDA-approved. When AKT is genetically inhibited, SGK is overexpressed, rescuing the knockdown of AKT (unpublished data from the Holmen lab). Therefore, to decrease the proliferative effect of the PI3K pathway, combined inhibition of AKT and SGK remains a viable strategy. We report that inhibitors against AKT and SGK decrease melanoma cell proliferation in vitro. Furthermore, combined AKT and SGK inhibition results in decreased tumor progression and increased overall survival (p=0.0031) in a BRAFV600E-driven immunocompetent mouse melanoma model. These findings demonstrate that dual targeting of SGK and AKT may represent a novel therapeutic strategy to abrogate melanoma growth.
Childhood Opportunity Index as a Predictor of Autism Spectrum Disorder Diagnosis in Utah
Zachary Tripp, University of Utah
Faculty Mentor: Michele Villalobos, University of Utah
SESSION A (9:00-10:30AM)
POSTER A81
Significant research has shown that health and well-being are directly correlated to childhood poverty and socioeconomic status. Racial inequities exist when it comes to age of diagnosis and service access for kids with Autism Spectrum Disorders (ASD). This is the first study to date to examine the impact of neighborhood level resources and conditions on access to autism services using the Childhood Opportunity Index 2.0 (ChOI 2.0). The primary goal of this study is to examine whether local-level child opportunity can serve as a predictive factor for diagnosis of ASD in the state of Utah. This study included 3,500 unique children seen at the Child Development Clinic from 2018- 2022 (1,030 female; 2,469 male) 194 of whom received an ASD diagnosis and 3,306 who did not. We geocoded residential addresses obtained from families in Utah and linked each location with census tract-level ChOI data. Child Opportunity Index 2.0 is a publicly available surveillance tool that incorporates a total of twenty-nine traditional and novel attributes of neighborhood conditions split into three categories. We analyzed the distribution of ASD diagnoses across the sample. A logistic regression was performed to ascertain the effects of ChOI on the likelihood of an ASD diagnosis. This research is important because it can highlight diagnostic differences based on opportunity. Further research can be done to determine the causes for the disparities in order to develop possible interventions to promote early detection of autism in all children.
Pediatric Oncology Patients’ Conceptualization of Cancer Symptoms
Minahil Usman, University of Utah
Faculty Mentor: Lauri Linder, University of Utah
SESSION A (9:00-10:30AM)
POSTER A82
Background: Approximately 1 in 285 children in the U.S. are diagnosed with cancer before their 20th birthday. The short- and long-term symptoms experienced by these children disrupt their quality of life by restricting their ability to participate in daily activities, negatively affecting close relationships, as well as increasing feelings of distress and frustration. The purpose of this project is to describe how children with cancer between the ages of 6 to 12 characterize their symptoms and expressions they use in relation to these symptoms. Methods: This descriptive study involves analysis of cognitive interviews with children with cancer 6-12 years of age who participated in the Kids Instrument Development Study for Symptom Management (KIDS-SM) which is supporting the development of two instruments to measure aspects of symptom self-management among children with cancer. Transcribed interviews have been uploaded into Dedoose to support identification of statements and phrases specific to how the child describes symptoms as well actions the child describes taking in response to experiencing symptoms or to avoid experiencing symptoms. A constant comparative process will be used to develop a coding schema to identify common categories of responses. Results: Interviews have been completed with 21 children (11 girls, 10 boys; mean age: 10 years). Preliminary analysis reveal that children use a variety of expressions to relate symptom experiences, such as feeling pain or ‘hurt’, going cross-eyed, etc. Children describe specific roles for their parents and clinical teams and also speak about things they do independently to self-manage their symptoms such as reading books and taking Tylenol. Discussion; Understanding how children conceptualize their symptoms is vital to track to improve children’s experiences during cancer treatment. Understanding children’s perceptions of these symptoms while also considering interpersonal, intrapersonal, and transpersonal relationships and environments can enable a more comprehensive, individualized, and sensitive approach to care.
Characterizing SPTLC3 Polymorphisms Associated with Circulating Ceramides
Alex Wiedemann, University of Utah
Faculty Mentor: Marcus Pezzolesi, University of Utah
SESSION A (9:00-10:30AM)
POSTER A83
Introduction. Obesity roughly affects one third of adults in the United States and is often a precursor to various comorbidities, including diabetes, hypertension, and dyslipidemia. Studies have reported that ceramides, a precursor to complex sphingolipids, are increased in obese and diabetic patients and are drivers for metabolic disease. Previously published genome-wide association studies (GWAS) of circulating ceramides have identified reproducible associations with single nucleotide polymorphisms (SNPs) near the SPTLC3 gene. However, the functional consequences of these SNPs are unclear. Here, we aim to identify variants effecting the expression of SPTLC3, which may have a role in driving dysregulated ceramide levels. Methods. We focused on SNPs that were genome-wide significant (p ≤ 5×10-8) from the National Human Genome Research Institute – European Bioinformatics Institute (NHGRI-EBI) GWAS catalog that are associated with various circulating ceramides and are within 100 kilo-base pairs of SPTLC3. Identified SNPs were examined for association with gene expression using the Genotype Tissue Expression Project (GTEx) and annotated with functional regulatory information from the Encyclopedia of DNA Elements (ENCODE). The RegulomeDB database was also used to annotate putative regulatory potential and identify predicted transcription factor binding motifs. After characterizing these SNPs, we designed and performed luciferase-based reporter assays for each SNP to determine their consequence on reporter activity. Results. We identified 7 SNPs of interest that are associated with Cer(d18:1/18:0), Cer(d18:1/22:0), Cer(d18:1/24:0), Cer(d18:1/24:1), and Cer(d18:1/26:0) species. All SNPs are strong expression quantitative trait loci (eQTLs) for liver-specific expression of SPTLC3 (p ≤ 5.3×10-12), though, only two SNPs fall within candidate cis-regulatory elements from ENCODE. After performing luciferase-based reporter assays, we identified one SNP, rs4814175, that demonstrates reduced luciferase activity. This SNP has a predicted binding motif for transcription factors GATA2 and ALX1 and may be functionally important in regulating SPTLC3. Conclusion. We identified rs4814175 as a potential driver for decreased SPTLC3 expression seen within human gene expression data. This SNP may impact binding of two potential transcription factors and may be a contributor to dysregulated circulating ceramides levels. Additional research is needed to fully understand the genetic drivers of ceramides.
Sequence learning across memory domains
Clara William, University of Utah
Faculty Mentor: Genevieve Albouy, University of Utah
SESSION A (9:00-10:30AM)
POSTER A84
Previous research suggests that memory systems supporting declarative and motor learning are not independent, sharing common processes. However, there is no direct empirical evidence of such between-memory-domain similarities. The goal of this study was to address this knowledge gap.
We designed a new version of the serial reaction time (SRT) task, with pictures of objects as visual cues to trigger motor responses. There are three different versions of the task: an object sequence task (sequence of objects paired with random key presses), a motor sequence task (sequence of key presses paired with random objects), and a control task (random keys and objects). Thirteen healthy participants (age: 18-30, 8 female) learned the two sequence tasks 4 hours apart. Consolidation of the sequence tasks was assessed with an overnight retest. Behavioral analyses of response time indicate that participants learned object and motor sequences to the same extent (block effect [BE]: F(19,228)=20.29, p<0.001); condition effect [CE]: F(1,12) =2.87, p=1.12; condition by block effect [CBE]: F(19,228)=1.19, p=0.26). Data acquired during the post-training test showed that performance plateaued similarly between conditions (BE: F(3,30)=1.54, p=0.22; CE: F(1,10)=0.54, p=0.47; CBE: F(3,30)=0.27, p=0.847). During the overnight retest, performance improved similarly between conditions (BE: F(3,30)=6.63, p=0.001; CBE: F(6,60)=4.19, p=0.001). Performance differed between conditions (CE: F(2,20)=22.04, p<0.001) such that both sequence tasks performed faster than the random task, and performance was similar across sequence tasks. These results indicate that our newly designed SRT task allows memory development from different domains in one training day. There was similar retention of the sequence-specific knowledge across memory domains during the overnight retest. Moving forward, analyses of neuro-imaging data will unravel the neural processes supporting sequence learning across memory domains.
Does an audiologist’s person-centered discourse during a hearing aid orientation effect the patient’s self efficacy?
Tess Crawford, Utah State University
Faculty Mentor: Brittan Barker, Utah State University
SESSION A (9:00-10:30AM)
POSTER A87
This study aimed to determine whether the manner in which a videoed clinician orients an individual to hearing aids (person-centered (PC) or clinician-centered (CC)) affects their processing fluency and comprehension of the material. Furthermore, we were curious if such effects are moderated by the individual’s health literacy. This study employed a between-subjects experimental design. The independent variable was delivery method (person-centered (PC), clinician-centered (CC)). The dependent variables were processing fluency rating and comprehension accuracy; health literacy served as moderator. 100 participants will be recruited via Prolific (2022), an online paid service to recruit participants and conduct behavioral studies. Participants must be 18 years or older, must communicate confidently in spoken and written English, have self-reported typical hearing, and self-reported typical cognitive functioning. During the study, each participant first completed a health literacy measure, The New Vital Sign (Weiss et al., 2005). Participants were then randomly designed to a video stimulus (PC or CC). The PC video included dialogue aspects such as, avoiding lengthy details, clearly explaining tasks with a hearing aid as a model, and refraining from the use of medical jargon. The CC video highlighted multiple pieces of information simultaneously, provide lots of details and superfluous information, and include a large amount of medical jargon. After the participant finished watching their assigned video, they completed the processing fluency survey via a 1-7 Likert scale, as well as 5 brief multiple-choice, comprehension questions about hearing aids. We are currently in the process of completing data collection. However, we plan to calculate descriptive statistics, and conduct a regression analysis to analyze our data. We predict that participants who viewed the video of an audiologist orienting the research participant in a person-centered (PC) manner will have comparatively higher comprehension accuracy and processing fluency scores than participants viewing a similar video of an audiologist orienting their patient to hearing aids in a clinician-centered (CC) manner. Furthermore, we predict that participants’ health literacy levels will moderate this relationship. Communication challenges between well-educated clinicians and their patients can result in miscommunications, and poor motivation to continue health care and interventions, which can have detrimental effects to individuals’ overall health and wellbeing. In audiology, hearing aid orientations, are often standardized and clinician centered. We predict that our data will support the need for audiologist to communicate more effectively with their patients in a patient-centered manner (e.g., use minimal jargon). This may ultimately ensure that patients could put their cognitive effort into understanding how a diagnosis/treatment applies to them and their care instead of working so hard to decipher what an audiologist is sharing. Such a facilitated understanding could lead to improved hearing aid use in future patients and improved overall hearing health.
Biomarker discovery in triple negative breast cancer using RNA-sequencing analysis
Jenna Birchall, Brigham Young University
Faculty Mentor: Brett Pickett, Brigham Young University
SESSION A (9:00-10:30AM)
POSTER A93
Breast cancer is the most common form of cancer, and afflicted over 2.2 million people in 2020. The sheer volume of patients that are afflicted with breast cancer warrants the need to continue research and discovery efforts to improve treatment options. Triple negative breast cancer (TNBC) affects 10-15% of breast cancer patients. Unlike other forms of breast cancer, TNBC does not have estrogen or progesterone receptors and makes little to none of the HER2 protein. Due to the lack of these biomarkers that are typical treatment targets for other kinds of breast cancers, hormone therapy and drugs that target other breast cancers are generally ineffective against TNBC. This leaves chemotherapy and radiation therapy as the main treatment options. Although chemotherapy and radiation have treatment benefits, the recurrence rate after treatment is around 40%. Furthermore, these treatment options are very detrimental to the body, resulting in a weaker patient and a necessary recovery time between treatments. In this study, we analyzed publicly available RNA-sequencing data to identify the upregulated and downregulated transcriptional mechanism(s) that play a role in TNBC compared to healthy breast tissue. The analysis of the RNAseq data was completed with the Automated Reproducible Modular Workflow for Preprocessing and Differential Analysis of RNA-seq Data (ARMOR), which identified differentially expressed genes. The ARMOR program trims, maps, and quantifies the mRNA sequencing reads to the human transcriptome for each sample. We then applied a Random Forest algorithm, which is an artificial intelligence-based classification method to identify new biomarkers that best differentiate TNBC cells from healthy cells.which may expand the treatment options for TNBC. We identified specific transcriptional biomarkers for TNBC that could be used as therapeutic targets. These novel targets may broaden the efficacy of treatments for patients with TNBC.