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Multivalent administration of dengue E dimers on liposomes elicits type-specific neutralizing responses without immune interference
Get PDFThe four serotypes of dengue virus (DENV1-4) are a major health concern putting 50% of the global population at risk of infection. Crucially, DENV vaccines must be tetravalent to provide protection against all four serotypes because immunity to only one serotype can enhance infections caused by heterologous serotypes. Uneven replication of live-attenuated viruses in tetravalent vaccines can lead to disease enhancement instead of protection. Subunit vaccines are a promising alternative as the vaccine components are not dependent on viral replication and antigen doses can be controlled to achieve a balanced response. Here, we show that a tetravalent subunit vaccine of dengue envelope (E) proteins computationally stabilized to form native-like dimers elicits type-specific neutralizing antibodies in mice against all four serotypes. The immune response was enhanced by displaying the E dimers on liposomes embedded with adjuvant, and no interference was detected between the four components
Dengue virus IgG and serotype-specific neutralizing antibody titers measured with standard and mature viruses are associated with protection.
Get PDFRecent work demonstrates the limitations of the standard dengue virus (DENV) neutralization assay to predict protection against dengue. We perform studies to compare how a commercial IgG ELISA, envelope domain III (EDIII) or non-structural protein 1 (NS1) binding antibodies, and titers from plaque reduction neutralization tests (PRNTs) using reference standard and clinical mature viruses are associated with dengue disease. Healthy children (n = 1,206) in Cebu, Philippines were followed for 5 years. High ELISA values (≥3) were associated with reduced dengue probability relative to naïve children (3% vs. 10%, p = 0.008), but antibody binding EDIII or NS1 from each serotype had no association. High standard and mature geometric mean PRNT titers were associated with reduced dengue disease overall (p < 0.01), and high DENV2 and DENV3 titers in both assays provided protection against the matched serotype (p < 0.02). However, while 52% of dengue cases had standard virus PRNT titers > 100, only 2% of cases had mature virus PRNT titers > 100 (p < 0.001), indicating a lower, more consistent threshold for protection. Each assay may be useful for different purposes as correlates of protection in population and vaccine trials
Sociodemographic and Health Factors Are Associated with Antimicrobial Resistance across Eight States in the United States
Get PDFRecent studies suggest that country-level socioeconomic factors may explain antimicrobial resistance (AMR) patterns better than antimicrobial usage (AMU), but it remains unclear whether this holds for sociodemographic and health variation within countries. We used metagenomic analysis of untreated sewage to cross-sectionally characterize the bacterial resistome as a proxy for AMR at 44 wastewater treatment plants across eight USA states between 2019 and 2020. We examined associations between AMR with site-specific sociodemographic and health indicators and AMU. Spatial autocorrelation analyses were used to identify clusters of AMR. Gradient-boosted multivariate regression trees were applied to evaluate individual and joint predictor effects on AMR. Outpatient AMU explained negligible variation in AMR, whereas predictors related to economy, income, preventive health care, access to health care, social welfare, housing, and racial/ethnic composition showed the strongest associations. These relationships were observed across individual resistance classes and their combinations and predicted AMR nonlinearly, with thresholds where AMR shows sharp increases (risk factors) or decreases (protective factors). Significant interannual differences in resistome and bacteriome composition were observed between 2019 and 2020. Although causal inference is limited, the findings suggest that local-level indicators of health, economic conditions, well-being, and development may play an important role in shaping AMR within countries
Rediscovering the Korean New Wave: Tracing the Tides of a Revolutionary Film Movement
Get PDFThis thesis traces the aesthetic, ideological, and stylistic legacies of the Korean New Wave---a film movement that originated out of South Korea during the late 1980s---as its cinematic strategies have manifested and evolved throughout later works of New Korean Cinema and contemporary Korean films. In addition to a historical analysis of the sociopolitical and institutional milieu from which Korean New Wave cinema emerged, this thesis examines these films' melding of realism with melodrama and their deft maneuvers between art and commercial film styles. Finally, through an aesthetic analysis of Lee Chang-dong's 2018 film Burning, this thesis explores how Korean political and cultural matters are conveyed through aesthetic channels of cinematic mood and affect.Bachelor of Art
Understanding the Drought Stress Rescue Pathway of Pseudomonas simiae Strain WCS417 using a Forward Genetic Screen
Get PDFWith a rapidly growing human population, sustainable and climate-resilient agriculture is crucial to our continued survival. Due to the increase in global warming, abiotic stresses such as drought have become more prevalent, significantly reducing crop productivity. Emerging innovative products containing cultures of microbes, labeled as biostimulants or biocontrol strains, have the potential to improve a plant’s response to such stressors. However, the molecular mechanisms by which these microbial-based products relieve drought stress remain unknown. Here, we used Pseudomonas simiae WCS417, a plant growth promoting rhizobacterium, to understand the mechanism of drought rescue of the model plant Arabidopsis thaliana. We hypothesized that specific P. simiae WCS417 genes conferred a fitness advantage to A. thaliana, allowing for it to thrive under drought stress conditions. Using a randomly barcoded-transposon library of WCS417 and in vitro assays, 2000 mutants were screened to define the genes responsible for conferring the drought rescue phenotype, resulting in 19 mutants displaying a loss in this phenotype. After rescreening and sequencing, three genes were implicated in conferring the drought rescue phenotype. The mutant strains were identified to be auxotrophic and involved in the amino acid synthesis of cysteine and tryptophan, which, when mutated, led to decreased colonization by WCS417 of A. thaliana. Furthermore, our results also indicate that colonization efficiency is important for drought rescue of A. thaliana by WCS417. Future studies can exploit these properties to aid farmers across the world increase agricultural outputs in drought-stricken regions and ensure self-subsistence.Bachelor of Scienc
Feasibility of Retrospective Data Collection for Corticosteroid-Induced Hyperglycemia in Acute Lymphoblastic Leukemia: A Pilot Study
Get PDFCorticosteroid therapy, integral to Acute Lymphoblastic Leukemia (ALL) induction chemotherapy, poses a significant risk of hyperglycemia, even in individuals without prior diabetes. Corticosteroid-induced hyperglycemia (SIH), defined as a random glucose level ≥ 200 mg/dL, is associated with increased in-hospital mortality, duration of hospitalization, and admission to an intensive care unit among hospitalized patients with undiagnosed diabetes. Given these implications, optimizing management strategies for SIH in ALL patients’ undergoing chemotherapy is crucial for improving clinical outcomes. This pilot study aims to evaluate the feasibility of conducting retrospective data collection on SIH in ALL patients, while identifying preliminary trends that may inform future prospective research. By assessing data availability, collection methods, and potential risk factors through comprehensive chart reviews of ALL patients at UNC Health System Hospitals who received their first cycle of chemotherapy and corticosteroids from April 4th, 2014, to June 30, 2023, this study establishes the groundwork for larger, hypothesis-driven research. The retrospective approach allows the utilization of real-world data to explore SIH trends in a challenging patient population. The findings will help shape the design and methodology of future prospective studies, enhancing their clinical applicability.Doctor of Pharmac
U.S. Presidential Candidate Image Within a Polarized Media, 1990-2000; 2012-2020
Get PDFThis research is designed to explore the relevance of a presidential candidate’s image to the average voter, how voters rate certain attributes, and what attributes they emphasize, with and without media playing an influence. The phenomenon of digitalized political campaigns and the question of how candidates are portrayed by the media has completely reworked how the American presidency can be assessed. With the prevalence of media in everyday life, an increasingly polarized image of the United States’ two-party system arises, with voter representation and opinion changing through the lens of polarized media. With an increasingly polarized choice set, the distribution of traits has become increasingly clustered toward the extremes, resulting in partisan perceptions of candidates becoming asymmetrical. Analyzing the nuanced effects of media polarization on perceptions of crucial political actors is imperative in understanding and determining the use and consumption of political media campaigns in future years.Bachelor of Art
Mapping Business Education in Pharmacy: Compliance to and Beyond the ACPE Standards
Get PDFThere is a growing need for newly graduated pharmacists to have essential business skills upon graduation of pharmacy school. In addition, there is a heightened interest amongst students entering pharmacy school to pursue non-direct patient care opportunities. To understand how pharmacy schools are incorporating business training into their curriculum to meet these demands, an environmental scan of the curriculum of the 140 Accreditation Council for Pharmacy Education (ACPE) Accredited pharmacy schools in the United States and Puerto Rico was conducted. Courses were included if they had any of the following key terms: analytics, business, entrepreneurship, finance, informatics, insurance, management, marketing and pharmacoeconomics. Of the collected courses, course descriptions were then analyzed to determine if they included business training beyond what is specified in the 2016 ACPE accreditation standards.
In total, 387 courses were found to teach business training beyond the accreditation standards. Of these courses, 39.5% were required, 40.8% were electives, and 19.6% were unknown. The most prevalent themes identified in the beyond accreditation courses were practice management (28.9%), finances (26.9%), marketing (18.3%), entrepreneurship (18.1%), and managed care (17.3%). It was identified that there are still gaps in the business training of pharmacy students, especially within their required curriculum. With the combined increased need for pharmacy graduates to have business skills and increased interest from pharmacy students to pursue non-direct patient care opportunities, closing these gaps in business training would be beneficial to better train pharmacy students for their careers. Doctor of Pharmac
Breastfeeding and Type I Diabetes: A Scoping Review
Get PDFThis study evaluates the engagement of research focusing on the experiences of lactating individuals with Type I diabetes, compared to non-diabetic lactating individuals. Despite known physiological changes during lactation, there is a lack of understanding regarding the unique challenges faced by lactating individuals with Type I diabetes. Research indicates that these individuals typically breastfeed for shorter durations than their non-diabetic counterparts. A scoping review methodology was employed to map the existing literature on breastfeeding experiences among individuals with Type I diabetes with a search of PubMed and CINHAL. An inclusion criteria created by the researchers guided the selection of relevant studies and 19 studies were implemented in the final extraction. Analysis revealed four main themes: 1) support from healthcare professionals and additional education, 2) the need to identify vulnerable populations, 3) psychological impacts surrounding breastfeeding, and 4) the limited studies on the long-term effects of diabetic breast milk for both mother and infant. The findings highlight the need to identify at-risk populations and provide targeted education and support to improve breastfeeding success. Recommendations include updating medical providers on current research, offering educational materials in various languages, and involving endocrine specialists in patient care. Further research is necessary to address existing gaps in care.
Keywords: Type I diabetes, breastfeeding, challenges, barriers, scoping reviewBachelor of Scienc
Reliability of remote at-home oscillometric blood pressure monitoring in community-dwelling children aged 3–17
Get PDFAs hypertension becomes more prevalent, remote assessment of blood pressure (BP) has been proposed as a method to improve BP management in the pediatric population. We investigated the reliability of at-home BP monitoring in children ages 3–17. This study was conducted at six sites across the United States. Children participated in three BP measurements on one occasion by caregivers at home and, on another separate occasion, by trained examiners in a clinic setting. The results were averaged and classified according to the 2017 Pediatric Hypertension Guidelines as normal BP, elevated BP, stage 1 hypertension, or stage 2 hypertension. We collapsed participants with elevated BP, stage 1 hypertension, or stage 2 hypertension into one group: above-normal. We examined the agreement between the caregivers’ and examiners’ BP readings and the ease of the measurement process. One hundred eighteen (118) children participated in this study (48.3% male; mean age 9.65 ± 4.52 years). Most caregivers (78%−93%) and examiners (88%−99%) rated elements of BP measurement as “easy” or “very easy”. Caregiver and examiners’ agreement on BP classification as normal or above-normal ranged from 75.00% to 90.16% across age groups. Caregiver and examiner BP concordance significantly differed by age group (p = .03) and was lower among children with above-normal BPs. Overall, most aspects of the remote BP measurement process were rated as easy, suggesting that remote monitoring of BP in children is feasible. Concordance of BP measurements by caregivers and examiners was high for children in the normal BP range. More research is needed on the reliability of home BP monitoring across the pediatric age range for those with above-normal BP