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Fluoroquinolone antibiotics have been known to cause severe, multisystem adverse side effects, termed fluoroquinolone toxicity (FQT). This toxicity syndrome can present with adverse effects that vary from individual to individual, including effects on the musculoskeletal and nervous systems, among others. The mechanism behind FQT in mammals is not known, although various possibilities have been investigated. Among the hypothesized FQT mechanisms, those that could potentially explain multisystem toxicity include off-target mammalian topoisomerase interactions, increased production of reactive oxygen species, oxidative stress, and oxidative damage, as well as metal chelating properties of FQs. This review presents relevant information on fluoroquinolone antibiotics and FQT and explores the mechanisms that have been proposed. A fluoroquinolone-induced increase in reactive oxygen species and subsequent oxidative stress and damage presents the strongest evidence to explain this multisystem toxicity syndrome. Understanding the mechanism of FQT in mammals is important to aid in the prevention and treatment of this condition.
ContributorsHall, Brooke Ashlyn (Author) / Redding, Kevin (Thesis director) / Wideman, Jeremy (Committee member) / Borges, Chad (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
Due to persistent undernutrition in India and the increased demands placed on a woman’s body during childbearing and lactation, the Indian government has implemented a program to provide supplemental nutrition packets to women in rural India. This study examines the factors influencing uptake of nutritional packets by lactating mothers in southern, rural Rajasthan. Women were recruited from 65 villages in Rajasthan, India (n=149, minimum of 2 per village) to evaluate the relationship of nutrition packet uptake and two factors--education levels and distance to the health center.
Level of education had little impact on whether or not women received the nutrition packet. Of those women with no education, 63.1% received the packet. Of those with any education, 63.9% got the packet.
In contrast, distance was strongly correlated with whether or not women received the packet. For example, of the women living within 200 meters of the health center, 93.2% received a nutrition packet. Of the women living between 250 meters and one kilometer of the health center, 68.4% received a nutrition packet. Of the women living over one kilometer from the health center, only 25% received a nutrition packet. The relationship between uptake of packets and women’s perception of distance to the health center was also explored. Out of 50 women who did not receive the packet, all of the women who said there was no health center in their village did live more than one kilometer from a health center. Of the women who lived between 250 meters and one kilometer from the health center, 40% felt it was too far. Of the women who lived more than a kilometer from the health center, 66.7% felt it was too far and 29.6% said there was no health center in their village. Again, it does not appear that ‘too far’ is just a default reason for women, but that actual distance, more so than education, is a major contributing factor in their ability to take the nutrition packet. These findings suggest that improving access to supplemental nutrition packets at the village level may increase uptake by the women.
Level of education had little impact on whether or not women received the nutrition packet. Of those women with no education, 63.1% received the packet. Of those with any education, 63.9% got the packet.
In contrast, distance was strongly correlated with whether or not women received the packet. For example, of the women living within 200 meters of the health center, 93.2% received a nutrition packet. Of the women living between 250 meters and one kilometer of the health center, 68.4% received a nutrition packet. Of the women living over one kilometer from the health center, only 25% received a nutrition packet. The relationship between uptake of packets and women’s perception of distance to the health center was also explored. Out of 50 women who did not receive the packet, all of the women who said there was no health center in their village did live more than one kilometer from a health center. Of the women who lived between 250 meters and one kilometer from the health center, 40% felt it was too far. Of the women who lived more than a kilometer from the health center, 66.7% felt it was too far and 29.6% said there was no health center in their village. Again, it does not appear that ‘too far’ is just a default reason for women, but that actual distance, more so than education, is a major contributing factor in their ability to take the nutrition packet. These findings suggest that improving access to supplemental nutrition packets at the village level may increase uptake by the women.
ContributorsJeffers, Eva Marie (Author) / Hruschka, Daniel (Thesis director) / Maupin, Jonathan (Committee member) / Cook, Jeffrey (Committee member) / Barrett, The Honors College (Contributor) / School of Human Evolution and Social Change (Contributor)
Created2015-05
Description
Bacteria play a vital role in the world ecosystem, more importantly human health and disease. The capability to differentiate and identify these microorganisms serves as an important research objective. In past years, separations-based approaches have served as a way to observe and identify bacteria based on their characteristics. Gradient insulator dielectrophoresis (g-iDEP) provides benefits in identifying serotypes of a single species with precise separation. Separation of Staphylococcus epidermidis in a single g-iDEP microchannel is conducted exploiting their electrophoretic and electrokinetic properties. The cells were captured and concentrated at gates with interacting forces within the microchannel to clearly distinguish between the two strains. These results provide support for g-iDEP serving as a separating method and, furthermore, future clinical applications.
ContributorsDavis, Paige Elizabeth (Author) / Hayes, Mark (Thesis director) / Borges, Chad (Committee member) / Jones, Paul (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor)
Created2015-05
Description
2015 marks the deadline for the UN Millennium Development Goal 5 to reduce global maternal mortality rate (MMR) by 75% since 1990. As of 2015, MMR has only been reduced by 45%. Many international organizations claim that more medically trained midwives can meet global maternal health care needs. This study investigates two major questions. What is the role of midwives in diverse international maternal healthcare contexts? How do midwives in these different contexts define their roles and the barriers to providing the best care for women? From May to August 2015, I conducted over 70 interviews with midwives in Netherlands, Sweden, Rwanda, Bangladesh, Australia and Guatemala, interviewing between 6 and 13 midwives from each country. The majority of midwives defined their roles as supporting women's individual capacities and power through normal birth, and knowing when to refer when high-risk complications arise. Although thematic barriers vary by country, midwives in all countries believed that maternal healthcare can be improved by increased collaboration between midwives and other health care professionals, better access to culturally appropriate services, and greater public awareness of the role of midwives.
ContributorsCarson, Anna Elizabeth (Author) / Hruschka, Daniel (Thesis director) / Maupin, Jonathan (Committee member) / School of International Letters and Cultures (Contributor) / School of Human Evolution and Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Background: High risk types of human papillomavirus (HPV) are known to cause cancer, including cervical (99%) and oropharyngeal cancer (70%). HPV type 16 is the most common subtype. Three antigens that are critical for integration or tumor progression are E2, E6 and E7. In this study, we developed a systematic approach to identify naturally-processed HPV16-derived HLA class I epitopes for immunotherapy development. Methods: K562 cells, which lack HLA expression, were transduced with each HPV16 antigen using lentivirus and supertransfected with HLA-A2 by nucleofection. Stable cell lines expressing each antigen were selected for and maintained throughout the investigation. In order to establish a Gateway-compatible vector for robust transient gene expression, a Gateway recombination expression cloning cassette was inserted into the commercial Lonza pMAX GFP backbone, which has been experimentally shown to display high transfection expression efficiency. GFP was cloned into the vector and plain K562 cells were transfected with the plasmid by nucleofection. Results: Expression of K562-A2 was tested at various time points by flow cytometry and A2 expression was confirmed. Protein expression was shown for the transduced K562 E7 by Western blot analysis. High transfection efficiency of the pMAX_GFP_Dest vector (up to 97% GFP+ cells) was obtained 48 hours post transfection, comparable to the commercial GFP-plasmid. Conclusion: We have established a rapid system for target viral antigen co-expression with single HLA molecules for analysis of antigen presentation. Using HPV as a model system, our goal is to identify specific antigenic peptide sequences to develop immunotherapeutic treatments for HPV-associated cancers.
ContributorsVarda, Bianca Marie (Author) / Anderson, Karen (Thesis director) / Borges, Chad (Committee member) / Krishna, Sri (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
How are perceptions of morality and disgust regarding meat consumption related to each other? Which factor is more salient in determining one's willingness to eat the meat of a specific animal? How do these answers vary across religious groups? This study investigates the ways that concepts like morality and disgust are related to food preferences and hopes to shed light on the mechanisms that enforce culturally sanctioned food taboos. The study compares 4 groups of people in the U.S.: Christians (n = 39), Hindus (n = 29), Jews (n = 23), and non-religious people (n = 63). A total of 154 participants were given surveys in which they rated their feelings about eating various animals. Data from Christian and non-religious groups exhibited similar patterns such as a high likelihood of eating a given animal when starving, while results from Jews and Hindus were consistent with their religion's respective food taboos. Despite these differences, morality and disgust are strongly correlated with one another in almost all instances. Moreover, morality and disgust are almost equally important considerations when determining willingness to eat when starving.
ContributorsParekh, Shaili Rajul (Author) / Hruschka, Daniel (Thesis director) / Jacobs, Mark (Committee member) / Barrett, The Honors College (Contributor) / School of Nutrition and Health Promotion (Contributor) / School of Human Evolution and Social Change (Contributor) / Hugh Downs School of Human Communication (Contributor)
Created2014-12
Description
The United States is experiencing an increase in the prevalence and influence of complementary and alternative medicine (CAM) in patient healthcare, reflecting the increasingly positive public and professional attitudes on the use of CAM therapies. Despite the growing presence of CAM in U.S. healthcare, there are still many barriers to integration. This study aims to reveal the attitudes of conventional, integrative and CAM practitioners concerning the major challenges of CAM's integration, explore their proposed solutions, and reveal any discrepancies in these attitudes among different types of practitioners. Twenty-eight practitioners were interviewed on the challenges in the five facets of CAM's integration: integration into hospitals, integration into medical schools, insurance coverage for CAM, licensing & regulation of CAM practitioners, and clinical research in CAM. The overall positive attitudes on the benefits of CAM's integration support previous research on the subject; however, the conventional practitioners were unable to extend these benefits to real-world application, and they were unaware of many of the challenges facing CAM's integration. The CAM practitioners attributed many of the problems facing integration to the inability of CAM's philosophy to comply with the current ideology of medical academia, health insurance model, and laws that govern the licensing and regulation of medical practitioners. The CAM and integrative practitioners perceived there to be a large resistance from conventional practitioners, specifically concerning the integration of CAM into education, providing insurance coverage for CAM, and the licensing and regulation of CAM practitioners. They attributed this to a perceived lack of research on safe and effective treatments in CAM. The conventional practitioner responses reflected this weariness of treatment effectiveness in their responses. However, the CAM and integrative practitioners believed these claims to be largely inaccurate, and constructed by the influence and manipulation of large-scale medical corporations and organizations. The participants believed that more evidence-based research in CAM, and increased public awareness in CAM therapies will force conventional practitioners to increase their knowledge in CAM, helping to alleviate their fears and skepticism of CAM therapies. By easing these concerns, dialogue can occur among practitioners of different modalities that will help to ensure a smooth integration of CAM and will raise the quality of patient healthcare by providing safe and effective resources for alternate forms of treatment.
ContributorsJohnston, Shantele Hanna Lee (Author) / Hruschka, Daniel (Thesis director) / Hurlbut, Ben (Committee member) / Barrett, The Honors College (Contributor) / School of International Letters and Cultures (Contributor) / School of Human Evolution and Social Change (Contributor)
Created2014-05
Description
Fat-stigma has become a popular topic of research in recent years as obesity and Western ideals have made their way around the globe. Previous studies have found that the internalization and expression of body norms can vary dramatically depending on location, gender, and many other cultural factors. Differing levels of body satisfaction have been linked to the internalization of these norms, and the development of low body esteem can result in many physical and emotional problems. Although there is an abundance of research on the topic of fat-stigma, few studies have investigated the related, but seemingly independent, topic of the ideal thin body. Furthermore, limited research has looked directly at body size stereotypes in Guatemala, and those that have, focused solely on Guatemala City. Furthermore, no previous cross-cultural analyses were found comparing body norms among US and rural Guatemalan adolescents. By surveying 9-10 year old students in Acatenango, Guatemala and Phoenix, Arizona, this study compared the preferences as well as stereotypes for average, thin, and fat body sizes in these two contexts. The results of this study illustrate a contrast between a fat-negative and a thin-negative culture, and highlight the complexity of the emergence of body norms around the world. We find that, in contrast to previous studies, neither the western ideal thin body nor obesity stereotypes have been internalized in Acatenango. Furthermore, negative evaluations of fat bodies and positive evaluations of thin bodies seem to be made independently of each other. Americans had a much higher prejudice against fat children and were more likely to be thin-positive (OR=1.997), while Guatemalans were more likely to be thin-negative. On average, the American students were much more polarized in their judgments on different body sizes, and experienced greater levels of body dissatisfaction. Finally, American students favored an ideal figure over one size smaller than Guatemalan students. Results suggest that there are still rural communities that have not been entirely affected by the spread of western body norms.
ContributorsCole, Dawn Michelle (Author) / Maupin, Jonathan (Thesis director) / Hruschka, Daniel (Committee member) / Barrett, The Honors College (Contributor) / School of Geographical Sciences and Urban Planning (Contributor) / School of Human Evolution and Social Change (Contributor)
Created2013-12
Description
Africa is the area of the largest economic water scarcity on earth, with multiple countries, political systems, and geographies involved. Additionally, water scarcity affects more countries in sub-Saharan African than anywhere else on earth, with consequences like waterborne diseases, loss of agricultural development, educational setbacks, and security threats. This thesis synthesizes data on the diverse geographies and politics involved in building a sustainable African water system. It presents historical and present technologies, costs, and problems implementing sustainable potable water solutions, and suggests regional differences and individualized solutions, pointing out advantages and disadvantages of damming, boreholes, open wells, open-source water, and sewer systems. It goes on to discuss grant programs for water and wastewater solutions and technologies. Finally it addresses two divergent, yet equally important data models for African water planning, combining their contributions in order to gain insight into the problem that neither alone can. The research overlaps aquifer and demographic data to see where water should be a priority in Africa. The author finds that hydrology as well as demographic data, when combined, point to the greatest water need in the Sahel. However, many growing cities are situated in areas with high aquifer levels making borehole technology some of the most economical as well as sustainable water sourcing. Recommendations include cultural humility, attention to political and environmental consequences of solutions, and cost-effective ways of addressing the lack of access to clean drinking water in Africa.
ContributorsBarbur, Denisa Teodora (Author) / Gaughan, Monica (Thesis director) / Hruschka, Daniel (Committee member) / Barrett, The Honors College (Contributor) / School of International Letters and Cultures (Contributor) / School of Human Evolution and Social Change (Contributor)
Created2014-05
Description
Protein AMPylation is a recently discovered and relatively unstudied post-translational modification (PTM). AMPylation has previously been shown to play an important role in metabolic regulation and host pathogenesis in bacteria, but the recent identification of potential AMPylators across many species in every domain of life has supported the possibility that AMPylation could be a more fundamental and physiologically significant regulatory PTM. For the first time, we characterized the auto-AMPylation capability of the human protein SOS1 through in vitro AMPylation experiments using full-length protein and whole-domain truncation mutants. We found that SOS1 can become AMPylated at a tyrosine residue possibly within the Cdc25 domain of the protein, the Dbl homology domain is vital for efficient auto-AMPylation activity, and the C-terminal proline-rich domain exhibits a complex regulatory function. The proline-rich domain alone also appears to be capable of catalyzing a separate, unidentified covalent self-modification using a fluorescent ATP analogue. Finally, SOS1 was shown to be capable of catalyzing the AMPylation of two endogenous human protein substrates: a ubiquitous, unidentified protein of ~49kDa and another breast-cancer specific, unidentified protein of ~28kDa.
ContributorsOber-Reynolds, Benjamin John (Author) / LaBaer, Joshua (Thesis director) / Borges, Chad (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Life Sciences (Contributor)
Created2014-05