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Description
Ovarian cancer (OC) is the second most common form of gynecologic cancer and is the most fatal among all forms of gynecologic malignancies. Despite the pivotal role of metabolic processes in the molecular pathogenesis of OC, robust metabolic markers to enable effective screening, rapid diagnosis, accurate surveillance, and therapeutic monitoring of OC are still lacking. In this study, we present a targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabolic profiling approach for the identification of metabolite biomarker candidates that could enable expedited, highly sensitive and specific OC detection. Using this targeted approach, 90 plasma metabolites from many metabolic pathways of potential biological significance were reliably detected and monitored in 218 plasma samples taken from three groups of subjects (78 OC patients, 50 benign samples, and 90 healthy controls). Univariate significance testing and receiver operating characteristic (ROC) analysis revealed 7 metabolites with high predictive accuracy [area under curve (AUC) > 0.90] for distinguishing healthy controls from OC patients. The results of our multivariate model development informed the construction of a 5-metabolite panel of potential plasma biomarkers for enhanced discrimination of OC samples from benign specimens, exhibiting roughly 75% predictive accuracy using a 50% random-split training set. ROC analysis that was generated based on a logistic regression classifier showed enhanced classification performance relative to individual metabolites, with more than 75% accuracy using a testing data set for external validation. Pathway analysis revealed significant disturbances in glycine, serine, and threonine metabolism; glyoxylate and dioxylate metabolism; the pentose phosphate pathway; and histidine metabolism. The results expand basic knowledge of the metabolome related to OC pathogenesis relative to healthy controls and benign samples, revealing potential pathways or markers that can be targeted therapeutically. This study also provides a promising basis for the development of larger multi-site projects to validate our findings across population groups and further advance the development of improved clinical care for OC patients.
ContributorsTurner, Cassidy D (Author) / Gu, Haiwei (Thesis director) / Shi, Xiaojian (Committee member) / School of Life Sciences (Contributor) / Sanford School of Social and Family Dynamics (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
How would you feel if you went to a pharmacy and the pharmacist gave you a medication with a prescription label that was written in a different language? How would you know how to properly take the medication, or what the dosage information was? Limited-English proficient patients often experience this confusion when they have to take medication with a prescription label written in English. As the United States becomes increasingly more culturally and linguistically diverse, certain populations face a higher risk of adverse medical incidents occurring because of communication barriers associated with their language ability (Agency for Healthcare Research and Quality, 2012). In order to minimize these medical incidents and ensure a high quality of care for limited-English proficient patients, healthcare providers must educate the public on useful approaches.
ContributorsRayyan, Danielle Sam (Co-author) / Rayyan, Danielle (Co-author) / Collins, Michael (Thesis director) / Esquibel, Ivy (Committee member) / School of Life Sciences (Contributor, Contributor) / Dean, W.P. Carey School of Business (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Background: Homelessness has a culture based on environment and many volunteers working in a clinical setting with people experiencing homelessness do not have personal experiences or training that prepares them to deliver culturally competent care. This study aimed to determine if implementation of a cultural competency intervention was effective in increasing volunteers’ comfort level with communicating with people experiencing homelessness and meeting their needs.
Method: Participants completed a survey regarding their comfort level in interacting with people experiencing homelessness and their preparedness in meeting their specific needs before and after receiving an educational presentation on cultural competency with working with people experiencing homelessness. The survey questions comprised Likert scale and open-ended answers.
Results: Of the Likert scale pre and post surveys, statistically significant differences were observed for questions 1 through 4, but not question 5.
Discussion: The results indicated support for the benefit of cultural competency training for student volunteers serving people experiencing homelessness in a clinical setting.
Method: Participants completed a survey regarding their comfort level in interacting with people experiencing homelessness and their preparedness in meeting their specific needs before and after receiving an educational presentation on cultural competency with working with people experiencing homelessness. The survey questions comprised Likert scale and open-ended answers.
Results: Of the Likert scale pre and post surveys, statistically significant differences were observed for questions 1 through 4, but not question 5.
Discussion: The results indicated support for the benefit of cultural competency training for student volunteers serving people experiencing homelessness in a clinical setting.
ContributorsRokhlin, Pnina (Author) / Dahl Popolizio, Sue (Thesis director) / Ervin, Bonnie (Committee member) / School of Life Sciences (Contributor) / Sanford School of Social and Family Dynamics (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Small cell carcinoma of the ovary (SCCOHT) is a rare ovarian cancer affecting young women and characterized by mutation in SMARCA4 and silencing of SMARCA2, two tumor suppressors that function as ATPases in the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex. SCCOHT patients face a 5-year survival rate of only 26%, but recently we have identified sensitivity of SCCOHT models to a natural product, triptolide. This study aims to ascertain the mechanism of action of triptolide. Previous SCCOHT epigenetic drug research has shown that some drugs reverse SMARCA2 epigenetic silencing to inhibit tumor growth, therefore it is hypothesized that triptolide acts the same and restores SWI/SNF function. Cells treated with triptolide have no change in SMARCA2 expression, suggesting that re-expression of epigenetically silenced tumor suppressor gene does not underlie its mechanism of action. Growth rates following triptolide treatment were observed in the presence and absence of SMARCA4, but no difference in sensitivity was observed. Thus, it is not likely that triptolide acts by restoring SWI/SNF. Others have observed that triptolide acts on xeroderma pigmentosa type B protein (XPB), a component of super-enhancers, which are DNA regions with high levels of transcription that regulate genes responsible for cell identity and oncogenes driving tumorigenesis. Both SCCOHT-1 and BIN67 cell lines treated with triptolide displayed lower expression of the super-enhancer associated MYC oncogene compared to untreated cells, supporting the theory that triptolide could be inhibiting super-enhancers regulating oncogenes.. A western blot confirmed reduced protein levels of RNA polymerase II and bromodomain 4 (BRD4), two essential components found at high levels at super-enhancers, in BIN67 cells treated with triptolide. ChIP-sequencing of Histone H3 Lysine-27 Acetylation (H3K27ac) marks in BIN67 and SCCOHT-1 cell lines identified super-enhancers in SCCOHT using tools CREAM and ROSE, which were mapped to neighboring genes associated genes and compared with the COSMIC database to identify oncogenes, of which the top 11 were examined by qRT-PCR to ascertain whether triptolide reduces their expression. It has been found that 6 out of 11 of the oncogenes examined (SALL4, MYC, SGK1, HIST1H3B, HMGA2, and CALR) decreased in expression when treated with triptolide. Thus, there is reason to believe that triptolide’s mechanism of action is via inhibition of super-enhancers that regulate oncogene expression.
ContributorsViloria, Nicolle Angela (Author) / Lake, Douglas (Thesis director) / Hendricks, William (Committee member) / Lang, Jessica (Committee member) / School of Life Sciences (Contributor) / School of Human Evolution & Social Change (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Birds maintain resting plasma glucose concentrations (pGlu) nearly twice that of comparably sized mammals. Despite this, birds do not incur much of the oxidative tissue damage that might be expected from a high pGlu. Their ability to stave off oxidative damage allows birds to serve as a negative model of hyperglycemia-related complications, making them ideal for the development of new diabetes treatments with the potential for human application. Previous studies conducted by the Sweazea Lab at Arizona State University aimed to use diet as a means to raise blood glucose in mourning doves (Zenaida macroura) in order to better understand the mechanisms they utilize to stave off oxidative damage. These protocols used dietary interventions—a 60% high fat (HF) “chow” diet, and a high carbohydrate (HC) white bread diet—but were unsuccessful in inducing pathologies. Based on this research, we hypothesized that a model of an urban diet (high in fat, refined carbohydrates, and sodium) might impair vasodilation, as the effect of this diet on birds is currently unknown. We found that tibial vasodilation was significantly impaired in birds fed an urban diet compared to those fed a seed diet. Unexpectedly, vasodilation in the urban diet group was comparable to data of wild-caught birds from previous research, possibly indicating that the birds had already been eating a diet similar to this study’s urban diet before they were caught. This may constitute evidence that the seed diet improved vasodilation while the urban diet more closely mimicked the diet of the birds before the trial, suggesting that the model of the urban diet acted as the control diet in this context. This study is the first step in elucidating avian mechanisms for dealing with diabetogenic diets and has potential to aid in the development of treatments for humans with metabolic syndrome.
ContributorsRenner, Michael William (Author) / Sweazea, Karen (Thesis director) / Johnston, Carol (Committee member) / Basile, Anthony (Committee member) / Dean, W.P. Carey School of Business (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Terrestrial crude oil spills compromise a soil’s ability to provide ecosystem services by inhibiting plant life and threatening groundwater integrity. Ozone gas, a powerful oxidant, shows promise to aid in soil recovery by degrading petroleum hydrocarbons into more bioavailable and biodegradable chemicals. However, previous research has shown that ozone can change the soil pH and create harmful organic compounds.
The research objective was to determine the short-term ecological toxicity of ozonation byproducts on seed germination of three distinct plant types (radish, lettuce, and grass) compared to untreated and uncontaminated soils. We hypothesize that the reduction of heavy hydrocarbon contamination in soil by ozone application will provide more suitable habitat for the germinating seeds. The effect of ozone treatment on seed germination and seedling quality was measured using ASTM standards for early seedling growth in conjunction with a gradient of potting soil amendments. Ozonation parameters were measured using established methods and include total petroleum hydrocarbons (TPH), dissolved organic carbon (DOC), and pH.
This study demonstrated the TPH levels fall up to 22% with ozonation, suggesting TPH removal is related to the amount of ozone delivered as opposed to the type of crude oil present. The DOC values increase comparably across crude oil types as the ozonation dose increases (from a background level of 0.25 g to 6.2 g/kg dry soil at the highest ozone level), suggesting that DOC production is directly related to the amount of ozone, not crude oil type. While ozonation reduced the mass of heavy hydrocarbons in the soil, it increased the amount of ozonation byproducts in the soil. For the three types of seeds used in the study, these changes in concentrations of TPH and DOC affected the species differently; however, no seed type showed improved germination after ozone treatment. Thus, ozone treatment by itself had a negative impact on germination potential.
Future research should focus on the effects of post-ozonation, long-term bioremediation on eco-toxicity. By helping define the eco-toxicity of ozonation techniques, this research can improve upon previously established ozone techniques for petroleum remediation and provide economic and environmental benefits when used for soil treatment.
The research objective was to determine the short-term ecological toxicity of ozonation byproducts on seed germination of three distinct plant types (radish, lettuce, and grass) compared to untreated and uncontaminated soils. We hypothesize that the reduction of heavy hydrocarbon contamination in soil by ozone application will provide more suitable habitat for the germinating seeds. The effect of ozone treatment on seed germination and seedling quality was measured using ASTM standards for early seedling growth in conjunction with a gradient of potting soil amendments. Ozonation parameters were measured using established methods and include total petroleum hydrocarbons (TPH), dissolved organic carbon (DOC), and pH.
This study demonstrated the TPH levels fall up to 22% with ozonation, suggesting TPH removal is related to the amount of ozone delivered as opposed to the type of crude oil present. The DOC values increase comparably across crude oil types as the ozonation dose increases (from a background level of 0.25 g to 6.2 g/kg dry soil at the highest ozone level), suggesting that DOC production is directly related to the amount of ozone, not crude oil type. While ozonation reduced the mass of heavy hydrocarbons in the soil, it increased the amount of ozonation byproducts in the soil. For the three types of seeds used in the study, these changes in concentrations of TPH and DOC affected the species differently; however, no seed type showed improved germination after ozone treatment. Thus, ozone treatment by itself had a negative impact on germination potential.
Future research should focus on the effects of post-ozonation, long-term bioremediation on eco-toxicity. By helping define the eco-toxicity of ozonation techniques, this research can improve upon previously established ozone techniques for petroleum remediation and provide economic and environmental benefits when used for soil treatment.
ContributorsJanuszewski, Brielle (Author) / Rittmann, Bruce (Thesis director) / Yavuz, Burcu (Committee member) / Civil, Environmental and Sustainable Eng Program (Contributor) / School of International Letters and Cultures (Contributor) / School of Politics and Global Studies (Contributor, Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
New genomic resources allow for the investigation of gene family diversity in genome-enabled reptiles. The Toll-like Receptor (TLR) gene family recognizes pathogen-associated molecular patterns (PAMPs) and coevolves with environmental pathogens which makes it a strong candidate for looking at the interplay between gene family diversification and host-pathogen coevolution. Using a new orthology curation pipeline and phylogenetic reconstruction, a novel gene expansion event of TLR8 was identified to be exclusive to crocodilians and chelonians with species-specific pseudogenization events. A new gene, TLR21-like, was identified as a part of the TLR11 subfamily. These findings uncover reptile-specific gene family evolution and provide indications of the role of habitat in this process.
ContributorsMorales, Matheo (Author) / Kusumi, Kenro (Thesis director) / Dolby, Greer (Committee member) / Scott, Peter (Committee member) / School of Mathematical and Statistical Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
There are currently no disease-modifying treatments to halt or attenuate the progression of Alzheimer’s disease (AD). Transgenic rodent models have provided researchers the ability to recapitulate particular pathological and symptomological events in disease progression. Complete reproduction of all features of AD in a rodent model has not been achieved, potentially lending to the inconclusive treatment results at the clinical level. Recently, the TgF344-AD transgenic rat model has started to be evaluated; however, it has not been well characterized in terms of its cognition, which is fundamental to understanding the trajectory of aging relative to pathology and learning and memory changes. Therefore, the aim of the current study was to identify cognitive outcomes at 6, 9, and 12 months of age in the TgF344-AD rat model. Sixty female transgenic (Tg) and wildtype (WT) rats were tested on the water radial arm maze, Morris water maze, and visible platform task to evaluate cognition. Results from the asymptotic phase of the water radial arm maze showed that the 6 mo-Tg animals had marginally impaired working memory compared to 6 mo-WT rats, and 12 mo-Tg rats had significantly impaired working memory compared to 12 mo-WT rats. The 9 mo-Tg animals did not demonstrate a significant difference in working memory errors compared to the 9 mo-WT animals. This pattern of impairment, wherein Tg animals made more working memory errors compared to WT animals at the 6 and 12 month time points, but not at the 9 month time point, may be indicative of an inflammatory response that proves helpful at incipient stages of disease progression but eventually leads to further cognitive impairment. These results provide insight into the potential earliest time point that prodromal cognitive symptoms of AD exist, and how they progress with aging. Brain tissue was collected at sacrifice for future analyses of pathology, which will be used to glean insight into the temporal progression of pathological and cognitive outcomes.
ContributorsBulen, Haidyn Leigh (Co-author) / Bulen, Haidyn (Co-author) / Bimonte-Nelson, Heather (Thesis director) / Presson, Clark (Committee member) / Conrad, Cheryl (Committee member) / Woner, Victoria (Committee member) / Peña, Veronica (Committee member) / School of International Letters and Cultures (Contributor) / Department of Psychology (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Background: Inadequate hydration can have several adverse effects on health. In children, it can negatively affect their health and cognitive performance. The effects of fruits and vegetables on the hydration of children have not been adequately studied. This study included 177 children in this age group and examined the contribution of fruits and vegetables (F&V) on total water intake (TWI).
Methods: Two-day dietary and fluid intake records as well as 24-h urine samples were collected from 177 children over different weekends. The dietary records were analyzed with Nutrition Data System for Research to obtain TWI from food (TWI-F) as well as TWI from fruits and vegetables (TWI-FV). The fluid intake data was used to determine TWI from liquids (TWI-L). The urine samples were analyzed for volume (UVol), urine osmolality (UOsm), urine specific gravity (USG), and urine color (UCol) to examine hydration. Age was categorized into 3, 4-8, and 9-13 y based on the Institute of Medicine (IOM).
Results: About 52% of the children did not meet water intake recommendations by IOM and 39.8% of the children were underhydrated based on elevated urine osmolality. The average TWI was found to be 1,911± 70 mL. TWI-F was observed to be 492±257 mL, while TWI-L was 1,419±702 mL. TWI-FV only contributed 200±144 mL. As expected TWI was significantly higher in the older children (9-13 y) than children in other age group (3 and 4-8 y). The average UVol was 709±445 mL, USG was 1.019±0.006, UOsm was 701±233 mOsm·kg-1, and UCol was a 3±1 (based on the urine color chart). Only urine volume seemed to be influenced by the age of the children as it was significantly higher for the children in the 9-13 y age group.
Conclusion: Nearly half of the children did not meet water recommendations by IOM and were underhydrated. Fruits and vegetables did not have a significant contribution to TWI. Dietary interventions to increase F&V consumption, lower consumption of SSB, as well as maintain proper hydration may benefit the health of children.
Methods: Two-day dietary and fluid intake records as well as 24-h urine samples were collected from 177 children over different weekends. The dietary records were analyzed with Nutrition Data System for Research to obtain TWI from food (TWI-F) as well as TWI from fruits and vegetables (TWI-FV). The fluid intake data was used to determine TWI from liquids (TWI-L). The urine samples were analyzed for volume (UVol), urine osmolality (UOsm), urine specific gravity (USG), and urine color (UCol) to examine hydration. Age was categorized into 3, 4-8, and 9-13 y based on the Institute of Medicine (IOM).
Results: About 52% of the children did not meet water intake recommendations by IOM and 39.8% of the children were underhydrated based on elevated urine osmolality. The average TWI was found to be 1,911± 70 mL. TWI-F was observed to be 492±257 mL, while TWI-L was 1,419±702 mL. TWI-FV only contributed 200±144 mL. As expected TWI was significantly higher in the older children (9-13 y) than children in other age group (3 and 4-8 y). The average UVol was 709±445 mL, USG was 1.019±0.006, UOsm was 701±233 mOsm·kg-1, and UCol was a 3±1 (based on the urine color chart). Only urine volume seemed to be influenced by the age of the children as it was significantly higher for the children in the 9-13 y age group.
Conclusion: Nearly half of the children did not meet water recommendations by IOM and were underhydrated. Fruits and vegetables did not have a significant contribution to TWI. Dietary interventions to increase F&V consumption, lower consumption of SSB, as well as maintain proper hydration may benefit the health of children.
ContributorsJohal, Ramanpreet Kaur (Author) / Kavouras, Stavros (Thesis director) / Suh, HyunGyu (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Cerebral lateralization describes the asymmetries between the two halves of the brain which results in side-specialized processing of certain functions. This phenomenon provides a selective advantage by promoting enhanced cognitive abilities. However, due to the plastic nature of lateralization, an individual’s lateralization is highly subject to change by many external factors, such as pollution, throughout its life. Additionally, lateralized regions are dependent on different contexts, so lateralized elements do not all experience the same effects. A common pollutant found worldwide is bisphenol-A (BPA), a critical component of many plastics. BPA is a known endocrine disruptor that can agonize and antagonize the functions of sex steroids. Other studies have demonstrated the importance of sex steroids in regulating the development of cerebral lateralization; BPA may similarly affect lateralization. A popular research animal for studying toxicology is the zebrafish. Its advantages include a fully sequenced genome, many human orthologs, and more importantly, expresses lateralized behaviors that are indicative of the strength of its cerebral lateralization. This experiment analyzed the effects of BPA exposure on visual lateralization of zebrafish. Given the role that sex steroids play in moderating lateralization, it was hypothesized that exposing zebrafish to BPA would diminish the strength of lateralization in the brain which would translate into reduced behavioral lateralization. To test this, one group was exposed to 0.01 mg/L BPA for one week and compared against a control group in their eye preference when approaching a visual cue. Two settings, a foraging context and a social context, were utilized to examine the scope of impairment in lateralization. The control group in both settings displayed similar strengths in behavioral lateralization with a left eye preference. However, the lateralized response faded completely with BPA treatment. This experiment demonstrates that BPA induces loss of lateralization and possesses similar impacts on mechanisms controlling investigatory behavior in these two contexts. Wild populations may encounter higher concentrations of BPA, and although there is greater variability in these exposures, this experiment proves that exposure even beyond critical periods of development can impair lateralization. Additional research will have to be conducted to identify the effects of BPA on other lateralized behaviors and sensory modalities to pinpoint the exact mechanisms through which BPA influences lateralization.
ContributorsHuang, Alexander (Author) / Martins, Emilia (Thesis director) / Suriyampola, Piyumika (Committee member) / Conroy-Ben, Otakuye (Committee member) / School of Life Sciences (Contributor) / School of Molecular Sciences (Contributor) / Dean, W.P. Carey School of Business (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05