Drug Discovery of Novel Targeted Therapeutics for Metastatic Breast Cancer

Metastatic disease is the primary cause of breast cancer mortality, due to the lack of effective therapy. The Rho GTPase Rac is integral for the promotion of cancer cell migration/invasion, proliferation, and survival. Since metastatic breast cancers often overexpress or exhibit high Rac activity, inhibition of Rac is a viable strategy against metastatic cancer. Recently, we characterized EHop-016, a small molecule that inhibits Rac activity of metastatic breast cancer cells more efficiently than previously available Rac inhibitors (IC50 of 1µM). EHop-016 inhibits the activity of the Rac downstream effector p21 activated kinase and cell migration of metastatic breast cancer cells. We also reported that EHop-016 at ≥ 25mg/kg body weight significantly reduced tumor growth and metastasis in mice. However, our recent pharmacokinetic study of EHop-016 in a mouse model demonstrated that the bioavailability of Ehop-016 needs to be improved for pharmacological development. The hypothesis is that improvement of the EHop-016 structure will provide probes with increased potency against Rac and, therefore, increased bioavailability. Several Ehop-016 derivatives have been tested for their effects on breast cancer cell viability using the MTT assay. We found one compound, HV-107, which at concentrations ≥1µM inhibits the viability of metastatic breast cancer cell lines MDA-MB-231 and MDA-MB-435 by 45%. The effects of HV-107 on the inhibition of Rac activation were tested by pulldown assays. At 250nM, HV-107 inhibits Rac activation by 55% in MDA-MB-231 and MDA-MB-435 cells. Taken together, our findings suggest HV-107 has potential as an anti-metastatic agent and should, therefore, be further characterized

The development of a comprehensive infection prevention quality audit tool for operating room theatres in a private health care environment

A Dissertation submitted to the Faculty of Health Science, University of the Witwatersrand, in fulfillment of the requirements of the degree of Master of Science in Nursing Education Johannesburg, June 2017Multi-resistant organisms, the involvement of numerous stakeholders in the OR as well as the complex procedural and technical advancements, especially in the private healthcare environment, justifies an evidence based infection prevention quality audit tool for an OR that is comprehensive. The purpose of the study was to develop a comprehensive infection prevention quality audit tool for operating room within a private healthcare environment. A three phased, multi-method study was conducted whereby phase one included the identification of statements in existing audit tools, policies and published articles. This was used to compile concourse statements that were used during phase 2 in the Q-sort data collection method, which allowed stakeholders (scrub- and anaesthetic nurses, CSD Managers, IPC- and OHS Coordinators and surgeons) to indicate what they want to be included in the IPC Audit Tool for operating room. A statement verification was conducted to expand the concepts that enabled the researcher to compile an audit tool. Subject experts and the researcher tested the degree of validity of the audit tool in phase three of the study. A descriptive analysis revealed that the results of the Q-sort event was inconclusive. The subject experts were unable to determine the degree of validity of the audit tool, which forced the researcher to test the audit tool in an OR. A Comprehensive IPC Control Quality Audit Tool was developed. The utilisation of the audit tool in an OR should be a well-planned event. Specific education and training of the multidisciplinary team regarding IPC in the OR should be considered.MT201

Examining the effects of living learning programs on first year success of undergraduates

This dissertation examines the relationship between living learning programs (LLPs) and student success at Boston University, a large, private research institution. The focus of this research was to better understand the distinctions between different types of living learning program formats (honors, academic, and special interest) and traditional housing in terms of the types of students they attract and what relationship they have with academic performance, retention, and student perception. Using the conceptual frameworks provided by Astin’s “I-E-O” model and Tinto’s longitudinal model of student departure, a mixed method design employing both quantitative (binary logistic and linear regression) and qualitative (interviews with LLP program faculty, staff, and student advisors) components was used. Results indicate that there were significant differences in student characteristics, academic performance, and perception between LLP participants and students in traditional housing. LLP participation was found to be positively related to retention, academic success and a student’s evaluation of the overall environment of the University. Academic LLP participation was linked to increased retention and first year cumulative GPA, while honors LLP participants were more inclined to rate their overall experience as excellent. These findings demonstrate that LLP format and composition are important in evaluating how these programs impact first year students. While research was limited to the students enrolled at a single institution, this study provides information about LLPs with varying level of academic integration, which can be useful to administrators looking to establish or review LLP programs on their own campus

The influence of values and other social and psychological factors on the dress and appearance of African American college students

The purpose of the study was to investigate values and other social and psychological factors influence on dress and appearance of African American college students (AACS). The dependent variable was dress and appearance. Independent variables consisted of external values (being well-respected, security, warm relationships with others, and sense of belonging) and internal values (self-respect, sense of accomplishment, fun and enjoyment, self-fulfillment, and excitement). Included in the independent variables were social factors (media and referents\u27 influence (peers and family)) and psychological factors (self-consciousness, self-confidence, fashion leadership, and shopping enjoyment). Social adaptation theory provided the theoretical framework. The theory encompasses the social and psychological aspects of an individual\u27s thinking and reasoning. The underlying basis of social adaptation theory states that information is absorbed into existing cognitive structures, such as an individual\u27s values. A web-based survey was used to collect data of 282 AACS, freshman through graduate level, on two college campuses in a U.S. southern state. It was emailed to students by university personnel. As an incentive to complete the survey, participants were offered a university logo item. External values had a positive relationship with this group of AACS\u27 dress and appearance. Internal values were most important in the daily lives of AACS in this study. Those internal values were sense of accomplishment, self-respect, fun and enjoyment and self-fulfillment. The most important value of all values was self-respect. Of the social factors, media was a better predictor of dress and appearance than family and peers. In regard to the psychological factors, all of the variables contributed to the influence of dress and appearance, with fashion leadership having the greatest influence. Hypothesis one: Internal and external values influence dress and appearance of AACS, was partially supported. Hypothesis two: Referents will be the most influential social factor on dress and appearance was not supported. Hypothesis three: Fashion leadership will be the most influential psychological factor on dress and appearance was supported. Dress and appearance of AACS was influenced by external values, media, and the psychological factors - fashion leadership, self-consciousness, self-confidence, and shopping enjoyment

Registered dietitians in school nutrition leadership and dietetic students\u27 consideration of school nutrition

School nutrition programs provide meals and snacks to nutritionally support students in their academic achievement. The importance of qualified leadership to maintain standards and provide quality these meals and snacks is important. Limited research has examined the benefits of registered dietitians providing school nutrition leadership. The purpose of this study was to evaluate the motivational aspects and job responsibilities influencing registered dietitians\u27 (RD) and senior dietetic students\u27 decision to pursue school nutrition leadership positions. The Southeast Food and Nutrition Services (FNS) division of the United States Department of Agriculture (USDA) region was the focus of the research. Web-based questionnaires were used to collect responses from members of the School Nutrition Services Dietetic Practice Group (SNSDPG) members and senior dietetic students from 22 Academy of Nutrition and Dietetic accredited didactic programs in this area. Reasons RDs (N = 158) selected school nutrition leadership and reasons dietetic students (N = 129) would consider selecting a position in school nutrition were examined and compared. Motivational aspects and job responsibilities providing satisfaction for RDs were identified. The reasons students would not select school nutrition as a career option were also examined. Key aspects influencing RD selection of school nutrition leadership positions were want to engage/work with people (M = 4.55; SD = 0.68) and achieved a positive outcome (M = 4.53; SD = 0.64). Employee opportunities and outcomes were identified as the aspects impacting RD selection. Student selection of potential school nutrition leadership positions was influenced by impact others\u27 health and well-being (M = 4.42; SD = 0.63), positive impact on preventing childhood obesity (M = 4.32; SD = 0.76) and influence others (M = 4.37; SD = 0.65). Students not selecting a school nutrition position were influenced by intentions to develop clinical dietetics knowledge (M = 3.51; SD = 1.10) and clinical skills (M = 3.36; SD = 1.11). Comparisons between RD and student selection of school nutrition responses differences were significant (p \u3c 0.0001) for aspects such as foodservice leadership skills, work schedule preference, make a difference in the world and preventing childhood obesity. Based on the results of this research, aspects influencing current RDs to select school nutrition appear to be associated with working with others to achieve a positive outcome. While the senior dietetic students demonstrated interest in school nutrition for the opportunity to make a difference in the world, specifically with health. Consideration of these aspects may be beneficial to school districts seeking to recruit qualified individuals, specifically RDs, into school nutrition leadership positions. Keywords: Leadership, job responsibilities, motivational aspects, school nutrition, registered dietitian

Nontraditional Students’ Perceptions of Using Google Docs in Traditional Settings

The problem this qualitative phenomenological study addressed was the lack of understanding of the experiences of adult learners and their perceptions of online tools and interactivity as they engaged in the use of Google Docs in a traditional entry-level writing course. The purpose of this study was to gain insight into adult learners’ perceptions of online tools and interactivity as they engaged in the use of Google Docs in an entry-level writing course. Knowles’s theory of andragogy and Puentedura’s model of substitution, augmentation, modification, and redefinition (SAMR) provided the conceptual framework. Data were collected from semistructured interviews with nine adult learners from two small liberal arts colleges in metropolitan Atlanta. The research question focused on the classroom experiences of adult learners in Freshmen composition using Google Docs and how their experiences affected their writing process. Notes and interview transcriptions were coded using a priori codes from SAMR and andragogy. Themes that emerged included a collaborative experience, engagement with peers, productivity from collaboration, and writing motivation. Positive and negative experiences in the themes of collaborative experience and productivity from collaboration were reported. Findings may inform the development of evidence-based strategies to support education and training programs for faculty, writing programs, and staff to better meet the unique needs of the growing population of adult learners

Characterization of Murine Cytomegalovirus m142 and m143 Essential Gene Products

Cytomegalovirus (CMV) is a species-specific virus belonging to the Herpesviridae family. This DNA virus causes severe disease or even death in newborns and immunosuppressed patients. Murine CMV (MCMV) provides an opportunity to study the role of various viral products in replication and pathology in the natural host. Successful replication of CMV in the host depends upon the expression of a cascade of viral genes: immediate early (IE), early (E), and late (L). To date only three MCMV IE proteins have been characterized (IE1, IE2 and IE3). Our laboratory recently identified a novel IE gene region within the Hind III I region of MCMV. These genes, m142 and m143, are members of the US22 gene family of HCMV, some of which are transcriptional transactivators. The m142 and m143 genes are also essential for viral replication in fibroblasts. The purpose of this dissertation was to characterize the m142 and m143 transcripts and proteins, as well as determine if the gene products function as transcriptional transactivators like some of the other US22 gene family members. Although the m142 and m143 transcripts were present during IE times, levels of these two transcripts increased during early times of viral infection and remained abundant during late times. The genes, m142 and m143, encode a 1.8 and 3.8 kb transcript, respectively. The m142 and m143 proteins (designated pm142 and pm143, respectively) encoded by these transcripts were present by 3 hours post infection and remained abundant at 12 and 24 hours post infection. Interestingly, pm142 and pm143 could not be designated as immediate early proteins, because they were not expressed in the presence of drugs that block viral growth at this specific stage within the viral replication cycle. Therefore, the m142 and m143 immediate early genes do not express detectable levels of protein until early times post infection. The pm142 protein is 43 kD protein, and the pm143 protein is 53 kD. The pm142 and pm143 proteins localized to both the nucleus and the cytoplasm at 3, 4 and 24 hours post infection. In transactivation studies, we tested the ability of pm142 and pm143 to activate the MCMV major immediate early promoter (M122–123) and the early e1 promoter (M112–113). In combination, MCMV pm142 and pm143 transactivated the MCMV major immediate early promoter and enhancer (MIEPE) in a dose dependent manner to at least 3 fold above basal levels. However, individually pm142 or pm143 failed to transactivate the MIEPE. Together, pm142 and pm143 also exhibited noncooperative effects with IE1 and 1E3 in the activation of the MCMV MIEPE. In combination, pm142 and pm143 failed to activate the early e1 promoter, but pm142 and pm143 cooperated with IE1 and 1E3 to activate this promoter. Activation of the e1 promoter by IE1 and IE3 increased from 30 fold above basal levels in the absence of pm142 and pm143, to as high as 100 fold above basal levels in the presence of pm142 and pm143. This was the first time it has been shown that other MCMV viral proteins assist in IE1/IE3 mediated transactivation of the e1 promoter or any other promoter, and these findings have important implications in MCMV replication