Health and Rehabilitation Sciences Undergraduate Research Theses and Honors Research Theses

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Undergraduate Research Theses and Honors Research Theses from the School of Health and Rehabilitation Sciences (formerly School of Allied Medical Professions). More about the School of Health and Rehabilitation Sciences Honors Program can be found at:

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    The ability of the Aurora-A inhibitor alisertib to potentiate the anti-proliferative effects of VEGFR inhibitors in glioblastoma cells
    (The Ohio State University, 2018-05) Mifsud, Caroline; Lehman, Norman; Guerau, Mireia
    Glioblastoma (WHO grade IV glioma) is the most common primary malignant brain tumor in adults, and is generally incurable. The prognosis is poor, with a median survival of only 14.6 months. Aurora-A, a serine-threonine kinase critical for a variety of cellular processes including centrosome duplication, spindle assembly, and mitotic exit, is widely overexpressed in glioblastoma. Additionally, malignant gliomas also possess high levels of vascular endothelial growth factor (VEGF), which is associated with pathological vasculogenesis and angiogenesis. Therefore, drugs that inhibit Aurora-A, in addition to VEGF and its receptor, are of interest in order to inhibit neovascularization and cellular proliferation. It was hypothesized that combining alisertib with a VEGFR inhibitor, such as cabozantinib or vandetanib, would work synergistically to inhibit glioblastoma cell proliferation and induce cell death via apoptosis. The glioblastoma cell lines U87 and U1242 were treated with a range of concentrations of alisertib and either cabozantinib or vandetanib. Glioblastoma cells were seeded at 600 cells/60-mm plate. After 72 hours of drug exposure, cell colonies were counted, and the percent survival was graphed relative to the control untreated cells. The results of these experiments were analyzed using Chou-Talalay and Bliss Independence models to test for synergism and determine their statistical significance. Results of in vitro colony formation assays suggest that alisertib works synergistically to inhibit cellular proliferation with both cabozantinib and/or vandetanib in both cell lines. Because of the lack of effective treatments available for glioblastoma, these results provide a basis for clinical trials including these drug combinations. The results of such clinical trials may expand the potential treatment options for this aggressive disease, and improve the lives of glioblastoma patients.
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    Can eccentric rehabilitation induce myelin plasticity below spinal cord injury in mice?
    (The Ohio State University, 2023-12) Phan, Richard; Basso, D. Michele
    Demyelination after contusive spinal cord injuries (SCI) causes neurological deficits including motor and sensory dysfunction. New research showed that plasticity occurs in myelin where learning complex skills greatly increases development of new oligodendrocytes (McKenzie, 2014). However, therapy-induced white matter changes after neurotrauma remains largely unknown. Some natural axon remyelination occurs around the SCI without rehabilitation, peaking around five weeks (Pukos, 2019). Recently, our lab showed that eccentric downhill treadmill walking induced white matter plasticity well-above the injury, in the cervical cord, after chronic thoracic SCI (Faw, 2021). Here, we examine the extent of myelin plasticity due to downhill training well-below the SCI in the lumbar cord where locomotion is organized. We hypothesize that there will be a robust degree of myelin plasticity in the lumbar dorsal columns, which will exhibit a positive relationship with the recovery of locomotor and sensory functions. Adult male and female mice (n=18) were randomly assigned to three groups; naïve (n=6), untrained SCI (n=6) with contusion (75 kilodyne) at T9 spinal column, and eccentric downhill treadmill trained (dhTM) SCI (n=6). To determine eccentric-induced white matter plasticity, we used PDGFRα-CreERT2: mT/mG mice to express green fluorescent protein (GFP) on newly differentiated oligodendrocyte cells upon tamoxifen administration. The injection occurred 29 days after SCI, and seven days prior to downhill training. The 13-day dhTM regimen used with 4 training bouts, each 5 min in length separated by 5 min rest breaks, on a 10% declined TM. Downhill training caused an increase in new mature oligodendrocytes (GFP+/CC1+) in the lumbar dorsal columns compared to the untrained groups (p=0.05). An increase in new mature oligodendrocytes after dhTM also showed a strong, positive correlation with recovery in sensory function (r=0.827; p=0.006). These findings may offer valuable insight into the application of eccentric rehabilitation as a therapy to treat white matter loss in the lumbar cord stemming from chronic SCI, ultimately improving locomotor and sensory function in people currently living with SCI.
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    Exhaustion of Tumor-Reactive CD8+ T-Cells in a Murine Model of Pancreatic Cancer
    (The Ohio State University, 2023-05) Hudson, Halea Kayla; Clutter, Jill
    Pancreatic cancer has a five-year survival rate of 11.5% and is ranked third in the United States for cancer-related deaths. Despite promising advances in other cancers, current treatments (chemotherapy and immunotherapy) are not as effective for pancreatic cancer. Improved outcomes, potentially mediated by immunotherapy, are associated with increased T-cell presence within the tumor microenvironment. We aim to assess the therapeutic impact via the phenotype and exhaustion status of these cells. To accomplish this, our study evaluates a KPC murine model of pancreatic cancer, genetically designed to mimic the key characteristics of pancreatic cancer in humans. This model also includes a tumor-associated antigen luciferase-SIYRYYGL for the detection and evaluation of antigen-specific T-cells. To develop this model, C57BL/6 male mice were injected subcutaneously with KPC-PK5L1932 pancreatic cancer cells, which include a tumor-associated antigen and luciferase for bioluminescent imaging of cells in vivo (PDX1-Cre/LSL-KRasG12D/p53R172H/wt/Luciferase-SIYRYYGL). Tumor growth was monitored over two months, and immune cells in the tumors, spleens, and lymph nodes were characterized using high-dimensional flow cytometry with an H-2Kb-SIYRYYGL dextramer reagent to detect antigen-specific T-cells. Consistent tumoral growth was observed over the course of the 51-day study. Analysis via flow cytometry of the infiltrating murine immune cell populations revealed a distinct antigen-specific (H-2Kb-SIYRYYGL) CD8+ T-cell population in the tumor which was minimally present in the spleen and lymph node. This subset of tumoral cells also showed a high expression of the exhaustion markers PD-1 and TOX compared to the other CD8+ T-cells in the spleen and lymph node, suggesting the localized exhaustion of T-cells in the tumor. The successful tumor growth and detection of antigen-specific T-cells and other immune cells via flow cytometry demonstrates that our KPC murine model of pancreatic cancer can effectively be used for further exploratory experiments and analysis of immune infiltration. The antigen-specific T-cells were identified as having phenotypes consistent with T-cell exhaustion, which was not prominently seen with the cells of the spleen or lymph nodes. With this model developed, future studies will further evaluate these immune cell populations and reveal the impact of chemotherapy and/or immunotherapy.
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    Sensory Processing Patterns in Children and Adults on the Autism Spectrum
    (The Ohio State University, 2023-05) Favorito, Abigail; Crasta, Jewel
    Introduction: Autism is a neurodevelopmental condition that manifests with differences in social-emotional reciprocity, nonverbal communication, and relationship development, along with restricted and repetitive behaviors and sensory processing issues (CDC, 2020). Although sensory atypicality is part of the diagnostic criteria for autism, there is limited research on sensory processing across the lifespan among those on the autism spectrum. This study examines sensory processing patterns in children and adults on the autism spectrum as compared to neurotypical children and adults. Methods: The Short Sensory Profile (SSP), a parent-reported questionnaire used to measure sensory behaviors, was collected for 48 child participants (autism: n = 24; typically developing [TD]: n = 24). The Adolescent/Adult sensory profile (AASP), a self-report questionnaire about everyday sensory experiences, was completed by 48 adult participants (autism: n = 24; neurotypical [NT]: n = 24). Analysis of Variance (ANOVAs) was used to analyze group differences and Pearson's correlations were used to examine correlations between sensory processing and age. Results: Children on the autism spectrum showed significant group differences in all SSP domains compared to the control group (p-values < .05). Adults on the autism spectrum had significant group differences in all four sensory quadrants as well as significant group differences in domain scores for activity level, visual, touch, and auditory processing (p-values < .05). For TD children, no domains significantly correlated with age, and in the autism group, taste/smell sensitivity (r = 0.479, p = 0.018) was the only domain that significantly correlated with age. For NT adults, taste/smell processing (r = -0.519, p = 0.009) and touch processing (r = -0.538, p = 0.007) were the only domains that significantly correlated with age, and low registration (r = -0.557, p = 0.005) was the only quadrant that significantly correlated with age. For autistic adults, no domains or quadrants significantly correlated with age. Conclusions: The results suggest that both children and adults on the autism spectrum demonstrate greater sensory processing concerns than the control group. Given the continued persistence of sensory concerns in adulthood, there is a need for more research on strategies to support sensory processing across the lifespan.
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    Do seasonal differences in the ejaculate of male mosquitoes affect the longevity of female Northern house mosquitoes?
    (The Ohio State University, 2022-08) Arkorful-Bondzie, Christiana; Meuti, Megan; Clutter, Jill
    Females of the Northern house mosquito, Culex pipiens, transmit West Nile virus to humans and animals throughout the summer. However, during the fall and winter females do not bite or transmit disease but survive the winter in a hibernation-like state called diapause. The male mosquitoes do not survive the winter, but instead mate with females in the fall who store their sperm inside of specialized organs called spermathecae. Diapause in female mosquitoes is a seasonal response that occurs in mosquitoes once they are exposed to short-day, winter-like conditions. Female mosquitoes that enter diapause cease blood feeding and thereby halt disease transmission. Although males do not survive the winter, they change their seminal fluids in response to seasonal cues. Additionally, mated females of the yellow fever mosquito, Aedes aegypti, live longer than virgin females. We therefore hypothesized that seasonal changes in the seminal fluids of males would influence the survival of the female mosquitoes. To determine whether the seasonal conditions the males were exposed to affected female longevity, long and short day-reared females were allowed to mate with long or short day-reared males and female survival was monitored weekly. Additionally, the longevity of virgin long day and short day-reared females was also measured. In both long and short-day conditions, we found that virgin females lived longer than mated females. Furthermore, while the photoperiod of the male mosquitoes did not influence the survival of female mosquitoes reared under long-day, summer-like conditions, short day-reared females that mated with short day-reared females lived significantly longer than those mated with long day-reared males. These findings lay the foundation for future work to uncover new ways that we can control this important disease vector.
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    No Relationship between Visual Reaction Time and High-Risk ACL Injury Biomechanics During Stroboscopic Vision in High-Performing Female Athletes
    (The Ohio State University, 2022-05) Harmon, Jakob; Onate, James; Caccese, Jaclyn
    Many factors influence the risk that young, active individuals have in injuring their anterior cruciate ligament (ACL), including their ability to process and respond to visual information when performing sports-specific movements. The degree to which, and if, visual dependence influences these movements in certain individuals is unknown. The purpose of this study was to determine if a relationship exists between visual reaction time (VRT) and an increase in biomechanics associated with ACL injury during a single leg drop landing performed under stroboscopic, perturbed, vision (SV) compared to full vision. A population of ten healthy female athletes (basketball and soccer, 19.83 ± 2.89 yrs., 169.80 ± 7.57 cm, 66.76 ± 9.11 kg) was studied. Participants performed three trials of a single leg landing from a height of 0.3 m under full and SV conditions for each leg in a three-dimensional motion analysis lab. Vision testing was then performed with a head mounted eye-tracking device. Changes in peak knee flexion (pKF), peak internal knee extension moment (piKEM), and peak vertical ground reaction force (pVGRF) between vision conditions were used to quantify changes in at-risk biomechanical variables. VRT was calculated by the system and presented in milliseconds. The alpha level was set a priori at p ≤ 0.05. A paired t-test was performed to find differences in performance between full and stroboscopic visual conditions. There were no significant changes in pKF (p = 0.11), piKEM (p = 0.74), and pVGRF (p = 0.39) between conditions. Pearson correlations were performed for each biomechanical variable with VRT for each participant. No significant (p > 0.05) correlational relationships were found between VRT and changes in pKF (r = -0.496, p = 0.15), piKEM (r = -0.234, p = 0.95), and pVGRF (r = -0.0821, p = 0.82). Future studies should be performed with larger populations and the testing of relationships between other high-risk ACL injury biomechanical variables with VRT and other vision variables.
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    Development and Validation of a Novel Three-Dimensional Rib Fracture Analysis Methodology
    (The Ohio State University, 2022-05) Stamper, David; Harden, Angela; Kang, Yun
    Rib fractures are the most prevalent injuries in motor vehicle crashes and contribute to increased patient morbidity and mortality rates. Fracture characteristics, such as fracture quantity, location, and severity are essential to evaluation of injury severity, treatment options, and patient outcomes. Clinically, these characteristics are commonly interpreted through chest radiographs or computed tomography (CT) scans. While imaging modalities used in rib fracture analysis are non-invasive, inaccuracies and false-negative diagnoses have been reported, especially when compared to postmortem dissection. The purpose of this study was to develop and validate a novel 3D methodology, developed to bridge the gap between methodologies, through comparison to postmortem rib fracture analyses. Post-test CT scans of seven postmortem human subjects (PMHS) tested in a high-speed, rear-facing frontal impact condition were utilized for data collection and analysis. The range of CT slices containing the thorax was uploaded to Materialise MIMICS research software to create a 3D model. All 24 ribs of each PMHS were isolated, saved as individual files, and analyzed to determine presence/absence of fracture. If fractures were present, further analyses to evaluate fracture characteristics (location, category, type, and group) were conducted. All data collected were compared to postmortem dissection data. One hundred sixty-eight ribs were analyzed with the presence of at least one fracture observed in 56 ribs. Seventy fractures were observed in the sample of 56 ribs. All ribs underwent comparisons for number of fractures identified while fracture location, category, type, and group were compared across 52, 53, 41, and 34 fractures, respectively. Statistical analysis revealed no significant difference between 3D and postmortem methodologies regarding measures of number of fractures and fracture location. Intraobserver accuracy was also assessed and demonstrated greater than 90% assessment agreement for all variables. Comparison of the two methods revealed that the 3D methodology is capable of producing measures of number of fractures and fracture location that are not different from postmortem methods of skeletal analysis. Future work could include a larger sample for analyses of significant differences and intraobserver accuracy. Ultimately, the 3D method would also require comparison to standard methods of imaging to demonstrate superiority in more detailed rib fracture characteristic analyses.
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    An Examination of the Social and Cultural Factors Surrounding Complementary Feeding Practices among Young African American Mothers with Infants 6 to 24 Months Old
    (The Ohio State University, 2022-05) Noble, ShyAnne; Adams, Ingrid
    African-American infants tend to have poorer diet quality compared to other demographic groups in the United States. The goals of the study were to examine the complementary feeding practices of young, low-income African American mothers with infants between the ages of 6 to 24 months and examine cultural and social factors influencing complementary feeding practices of these mothers towards their infants. Low-income, African-American mothers, between the ages of 18 and 30, living in Franklin County, Ohio were recruited through Facebook, daycare centers, and other organizations working with low-income populations. For this mixed-methods study, quantitative data were collected on the participants' demographics and qualitative data were collected on the participants' complementary feeding practices through virtual interviews. The data from the participants were analyzed using descriptive statistics and classical content analysis to determine the trends among the participants. The mean age of the participants was 28.29, most had some college experience or a college degree (87.5%), and 62.5% were not married. Qualitatively, four trends were discovered: pediatricians and other health professionals played a prominent role in early feeding decisions; cultures emerged in interesting ways; responsive feeding cues were used to determine hunger and fullness in their children; media did not influence early feeding decisions. Among the participants in the study, it was learned that direct influences (health professionals) were more influential than indirect (media) ones, participants followed recommended complementary feeding patterns, and media was not a strong influence on food choices. These findings imply that healthcare professionals should continue to be utilized in future research, WIC and other organizations have a positive impact on women's complementary feeding practices, and policies should be developed to educate pregnant women on complementary feeding.
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    What Does the Money Do? The Association Between Disproportionate Share Payments and Hospital Quality, Safety, Efficiency and Financial Health
    (The Ohio State University, 2016-05) Corrigan-Carias, Liam; White, Susan; Clutter, Jill
    The healthcare industry is experiencing a period of evolution and introspection. With Medicare and Medicaid expenses alone reaching $897.9 billion in 2015, providers are facing increased financial, governmental and public pressure to reduce costs, and at the same time deliver higher quality care. This study seeks to determine if there is a difference between the Disproportionate Share Hospital's (DSH), which receive financial assistance due to their high proportions of indigent patients and facilities that fail to qualify for DSH funding. The ACA will significantly reduce the Disproportionate Share Hospital provision to cut costs by 2022. The impact of this provision is not fully understood and this study seeks to determine if DSH funding provides a tangible benefit for the facilities that receive this supplemental assistance. The data for this study was attained from the Centers for Medicare and Medicaid Services and Hospital Compare. Facilities were grouped based on whether or not they received DSH funding, and their measured quality, safety, efficiency and financial health was analyzed. Findings suggest that there is no statistically significant association between DSH funding and hospital quality, safety and efficiency. There was, however, a nominal improvement in day's cash on hand and operating margin when comparing DSH to non-DSH facilities. The findings of this paper suggest that DSH funding should not be phased out, as its impact may go beyond the domain of patient care and affect a facility's financial viability, which in turn, may affect the community they serve.  
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    Leukocyte Profiles of House Wrens (Troglodytes aedon) in Northwestern Ohio: The Relationship Between Parental Health and Reproductive Success
    (The Ohio State University, 2016-05) Smith, Jacqueline; Augustine, Jacqueline; Snyder, John
    Evolution occurs when species adapt to changes in their environment. Pathogen prevalence in the environment may affect the health of an individual, and in turn, affect that individual's reproductive success. This study uses leukocyte profiles to quantify immune function in House Wrens (Troglodytes aedon), and to determine whether this aspect of the immune system affects individual mass, laying date, clutch size, and offspring size. Blood was drawn from 95 adult House Wrens and physical morphology was recorded. The nestlings' physical morphology was measured at ten days after hatching and averaged per brood. A principal components analysis was used to summarize four differentiated types of white blood cells with two principal component scores. The PC1 score indicated more heterophils and fewer lymphocytes, but was not related to any measures of reproductive success. A high female PC2 score, indicating more eosinophils and basophils, correlated with a smaller nestling tarsus. Eosinophilia and basophilia often result from an allergic immune response or parasitism. For females, clutch size decreased with a higher white blood cell (WBC) count. Male hematology did not relate to clutch size or nestling size. Neither PC1 nor PC2 correlated with laying date. These findings suggest that immune function positively impacts the number and size of offspring. This is the first study to describe the leukocyte profiles of wild House Wrens. Because it may be that only healthy birds can reproduce, future work should examine the hematology of non-breeding House Wrens to see if abnormal blood counts can account for their lack of reproduction.
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    Using Data to Describe Community Mobility for Individuals with Cognitive Disabilities
    (The Ohio State University, 2021-08) Stojkov, Ashley; DiGiovine, Carmen; Metzler, Sandra
    Objective: To describe usage patterns, utilization, and user interaction of a personal navigation smartphone application, WayFinder 3. Introduction: Transportation for individuals with cognitive disabilities presents several challenges. One potential solution to alleviate these barriers could be the use of mainstream technology such as a smartphone. One smartphone application that includes features to meet the personal navigation needs of individuals with disabilities is WayFinder. Methods: As a sub-component of the Mobility Assistance for People with Cognitive Disabilities (MAPCD) project, this descriptive study retrospectively described and categorized trip data from the implementation phase of the MAPCD project. Results: Data from the SMART (Specialized Media for Assistive Route Travel) Travel Manager, an online portal that allows a caregiver or community specialist to track a traveler in real-time while they are taking a trip using the WayFinder app, were evaluated on an individual basis to determine trip-end status and trip interaction types. The three trip-end statuses identified were completed, cancelled, and in-progress and the three trip interaction types identified were high user interaction, low user interaction, and other. The most common trip-end status for trips taken by travelers was cancelled, followed by completed and in-progress, and the most common trip interaction type taken by travelers was low user interaction, followed by other and high user interaction. Discussion: A method for categorizing trips was developed based on percentages of user interaction with waypoint notifications. By measuring user interaction and usage patterns of the WayFinder app, it can help determine if the app was effective in helping individuals travel in their communities. However, this metric for categorizing user interaction with trips is not the only method that should be used when determining perceived benefit of the WayFinder system.
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    Characterizing the role of claudin-5 in skeletal muscle fibrosis and cardiomyopathy
    (The Ohio State University, 2015-05) DeSalvo, Jennifer; Rafael-Fortney, Jill
    Our laboratory has identified reductions in the claudin-5 protein in investigations of both a dystrophic cardiomyopathic mouse model and human cardiomyopathy. Therefore, it is crucial to study the effects of isolated claudin-5 reductions in a claudin-5 knockdown (CKD) mouse model to determine whether loss of claudin-5 is sufficient to cause cardiomyopathy. Tamoxifen chow administration proved an effective method to knockdown claudin-5 expression in the myocardium while avoiding toxicity issues apparent with tamoxifen injections. Subsequent serial echocardiograms revealed that the experimental CKD mice exhibited initial physiological signs of a cardiomyopathic phenotype at 29 weeks of age. Immunofluorescence staining of these experimental mice also indicated a slight reduction and irregular staining patterns in the levels of claudin-5 and other cardiomyocyte membrane-extracellular matrix proteins. However, hematoxylin and eosin staining showed no signs of dilation or damage to the myocardium, indicating the lack of a cardiomyopathic phenotype at this timepoint. Furthermore, a dobutamine stress test did not induce a cardiomyopathic phenotype in experimental mice. This indicated the need to perform longitudinal echocardiograms with and without stress in future experiments to determine if these experimental mice develop cardiomyopathy as a result of claudin-5 reductions. Our laboratory also seeks to determine if claudin-5 ectopic expression is capable of maintaining the structural integrity of skeletal muscles in a dystrophin-deficient mouse model. Immunofluorescence staining of claudin-5 confirmed that dystrophin-deficient skeletal muscle inoculated with a rAAV6-claudin-5 vector containing 5×1011 viral genomes exhibited over 70% claudin-5-expressing fibers, and that only 22% of claudin-5 expressing skeletal muscle fibers contained central nuclei, an indicator of damage, compared to 48% in untreated dystrophic control muscles. Because there is ongoing damage in the dystrophin-deficient mouse model, the muscle fibers observed with cumulative degeneration and regeneration cycles may have been damaged prior to claudin-5 ectopic expression. Though this experiment is most clinically relevant to DMD patients that have ongoing damage to their striated muscles, further studies will be able to delineate the timing of a claudin-5-based therapeutic treatment in order to prevent damage prior to onset, rather than halting damage after onset. This data and its future implications may identify claudin-5 as a potential novel therapeutic target for treating DMD.
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    Novel stromal-derived oncogenic signals enhance Ras-mediated cell proliferation
    (The Ohio State University, 2015-05) Harrigan, Markus; Leone, Gustavo
    The appreciated, yet relatively unexplored, role of the complex tumor microenvironment in cancer progression provides a novel avenue to target cancer. Oncogenic signaling networks between stromal and cancer cells inherently exist, but have yet to be readily identified, and more importantly, understood at the molecular level. To systematically identify these signaling networks, we utilized the well-characterized vulvagenesis program of Caenorhabditis elegans (C. elegans). During vulva development, mesenchymal cells signal to adjacent epithelial vulva precursor cells (VPCs) through the Ras signaling pathway to promote the cell proliferation and patterning that form a mature vulva. This developmental signaling is akin to the cellular signaling interactions between stromal mesenchymal cells and epithelial cancer cells within a tumor. Consistent with their hallmark role in the formation of many human cancers, activating mutations in the RAS (let-60) oncogene in C. elegans lead to the hyper proliferation of epithelial VPCs, which presents as a multiple-vulva (MUV) phenotype. To elucidate signaling networks derived from the mesenchymal cells (which model stroma) that promote hyper proliferation in epithelial VPCs (which model cancer cells) in the context of mutant RAS (let-60), we conducted a genome-wide "stroma-specific" RNAi screen in C. elegans. The screen identified 60 "candidate genes", 42 with corresponding mammalian orthologs, whose activity in the mesenchymal cells contribute to the epithelial MUV phenotype. Subsequent studies were initiated to probe the mechanisms and pathways through which these "candidate genes" act. The overarching challenge is to translate the identified mammalian orthologs into clinically relevant findings that target the tumor microenvironment of Ras-driven cancers.
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    STAT3 inhibition of cholangiocarcinoma cell lines reduces viability and restricts the release of immunosuppressive cytokines in vitro.
    (The Ohio State University, 2015-05) Keenan, Kaitlin; Lesinski, Gregory B.
    Cholangiocarcinoma (CC) is the malignant transformation of epithelial cells originating from the bile ducts. This cancer has an abysmal 3 year survival rate of only 10% and is typically unresponsive to standard surgical and chemotherapeutic practices7. Therefore, novel treatment strategies are desperately needed against this malignancy. One important feature of CC cells is their autocrine secretion of interleukin-6 (IL-6)6,9,10. The secretion of IL-6 can activate numerous pro-oncogenic signaling pathways including STAT3 within the tumor cell, while simultaneously promoting immunologic changes in patients with advanced disease. We hypothesized that inhibition of Signal-Transducer and Activator of Transcription-3 (STAT3) pathway may elicit a dual effect by promoting apoptosis of human BC cell lines, and limiting the secretion of immunosuppressive cytokines from these cells. A panel of human CC cell lines (n=7) with various genotypic profiles demonstrated secretion of IL-6 (range 0-6593 pg/mL). Six of the seven lines assessed had constitutively phosphorylated STAT3 as determined by western blot. A novel small molecule inhibitor, FLLL100, can directly inhibit Tyr705 phosphorylation within the SH2 domain of STAT3, and induced apoptosis in the CC cell lines regardless of genotypic profile. These effects were observed within 24 hours of drug exposure at micromolar concentrations. Immunoblot analysis of PARP cleavage confirmed apoptosis. Exposure of CC cell lines to FLLL100 resulted in decreased secretion of IL-6 in culture supernatants. Together, these data indicate that the IL-6/STAT3 signaling axis plays a role in human CC survival and that targeting this pathway can limit immune suppressive factors derived from CC cell lines.
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    Examination of Dietary Patterns and FODMAPs Intake in Patients with Irritable Bowel Syndrome
    (The Ohio State University, 2020-05) Pei, Xuechen; Roberts, Kristen
    Background: There is growing evidence that supports the efficacy of a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) for symptom management in irritable bowel syndrome (IBS). Utilizing a food frequency questionnaire (FFQs) to determine current dietary practices of those with and without IBS allows the Registered Dietitian Nutritionist (RDN) to understand usual dietary intake as it related to FODMAP ingestion. Objective: To identify the average lactose, fructose, and polyol intake in people with and without IBS to gauge if there are differences in usual dietary intake. Methods: VioScreenTM, a web-based FFQ, was offered to all patients in the outpatient Gastroenterology, Hepatology, and Nutrition (GHN) clinic at The Ohio State University Wexner Medical Center to assess dietary patterns and lactose, fructose, and polyols intake. Those that completed the FFQ were stratified into those with and without IBS. Demographic data and health variables including age (yr), weight (kg), and BMI (kg/m2) were collected as part of the electronic FFQ. Results: Participants (N=140) were included in this study. Mean age was 43.0 ± 15.5 years with an average BMI of 28.2 ± 7.4 kg/m2. Those with IBS (n=24) were of similar age as those without IBS (41.9 ± 17.1 years vs 43.3 ± 15.2 years, respectively). No difference in the average fructose (36 g ± 38 vs 25 g ± 34; P = 0.156), lactose (14 g ± 10 vs 12 g ± 14; P = 0.655) and polyols (1 g ± 0.5 vs 1 g ± 0.6; P = 0.260) was detected between those with and without IBS. Conclusion: Patients with IBS do not consume significantly less fructose, lactose, and polyols compared to patients without IBS. Data suggests high- FODMAPs foods can trigger or worsen IBS symptoms. RDNs should evaluate the dietary patterns before the education of low-FODMAPs to ensure the education is targeting patient-specific high FODMAPs foods or potential trigger foods.
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    Differences in Chronic Health Conditions, Food Security Status, and Dietary Intake By Perceived Health Status In an Urban At-Risk Population
    (The Ohio State University, 2016-05) Hart, Hannah; Spees, Colleen
    In 2014, Ohio ranked 3rd nationally for rates of very low food security.1 Although food pantries provide emergency food assistance, these safety nets often fail to meet nutritional needs. The chronic lack of access to nutritious foods increases the risk of nutrition-related chronic disease and obesity. The objective of this study was to determine associations between: (1) self-reported health conditions and objectively measured biomarkers of health; and (2) perceived health status and actual health conditions in pantry clients.  Participants were recruited from two Southside food pantries and completed a Personal Health Assessment, and biometric screening including body mass index (BMI), blood pressure (BP), and glycated hemoglobin (A1C). Of the total participants (N=130), 29% self-reported known hypertension (HTN), 2% reported overweight or obesity (OW/OB), and 19% reported known type 2 diabetes (T2DM). Objective measures resulted in 90% of participants with HTN (BP>120/80 mmHg), 71% with OW/OB (BMI>25), and 24% with T2DM (A1C≥6.5%). Data were then stratified by self-reported health perception (Negative=“poor” or “fair;” Positive=”good”, “very good,” or “excellent”). Those with a negative health perceptions  were significantly more likely to report HTN (42%) as opposed to those with a positive health perceptions (19%, p=0.007). These findings indicate that local food pantry clients are underdiagnosed and untreated for chronic health conditions. Health perceptions were useful in estimating BP-related comorbidities only. Food pantries appear to be an excellent access point for screening vulnerable individuals in dire need of healthcare.
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    An investigation of biases in Patient Safety Indicator score distribution among hospital cohorts
    (The Ohio State University, 2016-05) Cua, Santino; White, Susan
    The Centers for Medicare and Medicaid Services (CMS) have implemented a hospital reimbursement system that incentivizes payment proportional to the quality of care delivered and performance on certain metrics. One such metric is the Agency for Healthcare Research and Quality’s Patient Safety Indicator 90 (PSI-90). It is composed of eight individual indicators designed to flag adverse patient events that are potentially preventable, such as post-operative wound dehiscence and accidental lacerations. CMS publicly reports four of these individual PSI scores (6, 12, 14 and 15) in addition to the composite PSI-90. Previous studies question the PSIs’ validity beyond screening purposes and furthermore question the underlying administrative data’s ability to accurately and reliably flag such events. This study looks to analyze biases in PSI score distribution for hospitals depending on teaching status, differences in patient demographics and lastly, interactions between teaching status and patient demographic factors and their ability to account for differences in PSI rates. Significant differences were found between teaching and non-teaching hospitals for PSIs 6, 12, 15 and 90 (p<0.01). Inpatient volume and patient severity (p<0.01) were found to be significantly different between teaching status cohorts. Lastly, significant differences in PSI scores were found between patient severity quartiles for PSI 6, 15 and 90 (p<0.05) and between socio-economic quartiles for PSI 6, 12, 15 and 90 (p<0.05); but interaction between patient severity and teaching status was only significant for PSI 90 (p<0.05) and between socioeconomic and teaching statuses for PSI 6 (p<0.05). These results indicate current PSI score distributions may be biased against teaching hospitals for 4 out of 5 PSI measures. Further studies will involve assessing the adequacy of risk-adjustment methodology for PSI metrics. Until then, use of PSI metrics to determine federal reimbursement can lead to bias against teaching hospitals.
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    Differences in Chronic Disease Prevalence, Knowledge, Behavior, and Self-Efficacy by Perceived Health Status in Food Pantry Clients
    (The Ohio State University, 2014-05) Mendelson, Maxine; Spees, Colleen; Taylor, Christopher
    To assess the relationship between perceptions of positive versus negative health and medical conditions, self-efficacy, and lifestyle behaviors in a cohort of adult food pantry clients. Using data from a 2012-2013 voluntary survey that was designed using a mix of new and validated survey questions to assess demographics, perceived health status, preventive healthcare, and food security status. Participants (n=250) were stratified by perceived health status (poor/fair; good/very good/excellent). We investigated unadjusted associations between perceived health status and self-efficacy (0-4), and prevalence of health behaviors, and medical conditions. The sample was 71.3% female, 53.4% white/Caucasian, 38.1% African American, 3.2% Latino/Hispanic with a mean age of 45.3. The prevalence of a “negative” health perception (poor/fair) was 52%. The negative health perception cohort presented with higher rates of chronic disease including hypercholesterolemia (34%), hypertension (56%), overweight/obesity (48%), and diabetes (22%). Those with a positive health perception reported greater self-efficacy related to making health care decisions, altering behaviors to impact disease management, and improving one’s own health status; however, they were also more likely to indicate they were making health behavior changes to address their chronic disease. These findings indicate that diagnosis of chronic health conditions and co-morbidities in food pantry clients may be associated with negative health-perceptions and lower levels of self-efficacy. This study provides preliminary evidence that perceived health status may be a useful indicator for screening high-risk individuals within food pantries.
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    Quantifying Variation in Human Rib Volumetric Bone Mineral Density (vBMD) and its Relationship to Fracture
    (The Ohio State University, 2019-05) Haverfield, Zachary; Hunter, Randee
    The human body is full of structural variation, especially in the skeletal architecture of different bones. This variation is dependent on the mechanical environment of the bone and its physiological purpose, which impacts its material and geometric properties. The relationship between these properties has been investigated in previous studies, which were largely focused on the structural and material variation of human long bones (femur, radius, tibia, etc.). It is still unknown if the variation of certain material and geometric properties found in the long bones are the same in the axial skeleton. As rib fractures are a main cause of fatality in drivers in motor vehicle crashes, it is essential to understand the multivariate factors that relate to bone quality and rib fracture risk. The purpose of this study is to investigate variation in volumetric bone mineral density (vBMD) along the length of the rib, cortical section modulus at the site of fracture (Z), and their relationship to structural properties to better understand differential fracture risk. In total, forty-six ex vivo mid-level ribs (5th-7th) were obtained from n=46 post mortem human subjects (PMHS) with ages ranging from 13-83 years. The 46 PMHS were divided into two different sub-samples, the age-matched sample and the physically tested sample, which was dependent on if the rib had been dynamically tested. Each rib was scanned using a 64 slice Philips Ingenuity Computed Tomography scanner (CT) at a consistent in-plane resolution of 0.167mm. Each rib was then dynamically tested in a 2-D bending scenario to simulate anterior-posterior thoracic impact. To investigate variation along the length of the rib, Phillips Intellispace, Dataviewer, and Skyscan CTAn software (Bruker) were used to calculate a vBMD value for volumes of interest (VOIs) located at the 30%, 50%, and 75% of total rib curve length (Cv.Le), the age-matched sample (n=44), as well as the location of fracture for the physically tested sample of the ribs (n=30). Z was collected from histological cross-sections taken from the site of fracture after dynamic testing. Finally, the sub-sample’s vBMD and Z were used to determine and calculate the Stress Strain Index (SSI) of the ribs. All data collected were normally distributed (p>0.15). One-way ANOVA demonstrated significantly different vBMD at all of the sites, 30% and the 50% sites (p<0.01), 50% and the 75% sites (p<0.01), and the 30% to the 75% site (p<0.01). The 30%, 50%, and the 75% sites were statistically tested against structural properties related to the rib, Linear Structural Stiffness (K), Total Energy (UTOT), and Peak Force (FPEAK). Using a linear regression, the 50% and 75% sites showed no significant predictability with any of these factors (p>0.05) as well as the first fracture site vBMD. The 30% site demonstrated no significant predictability between K or UTOT (p>0.05) but did demonstrate statistical significance when compared to FPEAK (p<0.05). When combining the fracture site vBMD with the fracture site Z, we were able to produce a multivariate factor, SSI. When compared to the structural properties, SSI was able to significantly predict UTOT, FPEAK, and K explaining large amounts of variation within the sample (p<0.001). However, Z alone explained slightly more variation within the sample than SSI could, excluding UTOT (p<0.0001). Quantifying vBMD along the length of the rib shows significant variation and is an essential part of understanding and predicting rib fracture risk. Likely, generalized scores are not enough to quantify and determine whole bone quality. Utilizing multifactor variables may prove useful in future analysis of bone quality assessment.
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    Reliability of Bioelectrical Impedance Analysis Devices in Assessing Body Composition
    (The Ohio State University, 2019-05) Huber, Emily; Buell, Jackie
    Background: The body composition of athletes is frequently evaluated in sports nutrition using bioelectrical impedance analysis (BIA) due to its non-invasive technology, wide availability, portability, and low-cost association. There is limited research assessing the reliability of the newer BIA devices on the market. Objective: Evaluate the reliability of four BIA devices across five serial encounters within typical uses. Methods: This second-generation study recruited a convenience sample of 8 Sports Nutrition Laboratory personnel to collect estimated body fat percentage at a total of 5 encounters over a two-week period on 4 selected BIA devices. The BIA devices included: InBody 770, Tanita Body Composition Analyzer SC-331, Omron HBF-306CN, and Greater Goods Digital Home Scale. The repeatability and variability of estimations for body fat percentage were analyzed across devices for five time points using the GLIMMIX procedure. Results: There were no significant differences in body fat percentage for each method across the five encounters (P>0.05). Variation in mean body fat percentage ranged from 0.8-1.5%. Deviations in individual body fat percentage across the 5 encounters were wide. Conclusions: The BIA devices used in this study may be reliable methods of tracking body composition over time. Professionals, as well as lay users, must be aware of the potential variability between body composition measures per assessment. The variation in body fat percentage between the devices encourages users to consistently use one device rather than multiple devices to collect body composition data.