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THE ASSOCIATION BETWEEN COGNITIVE FLEXIBILITY, CHILDHOOD ADVERSITY EXPOSURE, AND INTERNALIZING AND EXTERNALIZING SYMPTOMS
Get PDFAdversity exposure in childhood is associated with greater risk for developing internalizing and externalizing problems throughout childhood and adolescence (Henry et al., 2021). Adversity exposure may confer risk by impacting executive function, including reduced cognitive flexibility, due to the neurobiological consequences of increased stress hormone exposure (Kavanaugh et al., 2017). Previous research has linked adversity exposure to reduced cognitive flexibility in youth (Kavanaugh et al., 2017). Lower cognitive flexibility is also associated with internalizing and externalizing problems including depression, anxiety, and disruptive mood dysregulation disorder in youth and adults (Patwardhan et al., 2021; Stange et al., 2017; Braenden et al., 2023). Although cognitive flexibility mediated the pathway from childhood adversity exposure to depression in college students (Huang et al., 2022), to date, no research has investigated this pathway with internalizing and externalizing problems during late childhood. Investigating this pathway in late childhood is important because of the developmental trajectory of cognitive flexibility and emergence of internalizing and externalizing symptoms. The present study addresses gaps in the literature by testing whether cognitive flexibility mediates the association between adversity exposure and internalizing and externalizing problems in 9-11-year-old youth. Analyses were conducted with data from the Adolescent Brain and Cognitive Development Study (ABCD), a longitudinal dataset of youth (study wave 1: 9-11 years old, study wave 2: 10-12 years old), sampled across the United States (n = 11,868). Adversity exposure was calculated as the sum of 31 items from youth and parent reported measures of abuse and neglect, domestic violence, household mental illness and substance use, and economic hardship. Cognitive flexibility was measured by the NIH toolbox Dimensional Card sort Task. Parent reported externalizing symptoms were measured by the Child Behavior Checklist (Achenbach, 1991). Youth reported internalizing symptoms were measured by The Brief Problem Monitoring Survey (Achenbach et al., 2011). As expected, greater adversity exposure was associated with lower cognitive flexibility, and higher internalizing and externalizing symptoms 1 year later. Cognitive flexibility mediated the association between adverse events and youth self-reported internalizing symptoms and parent reported externalizing symptoms
A QUALITY-BY-DESIGN APPROACH FOR THE DEVELOPMENT OF INHALABLE DRY POWDERS FOR TUBERCULOSIS (TB) TREATMENT
No full textTuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), remains a pressing concern globally. The emergence of drug-resistant strains and the need for prolonged treatment regimens continue to complicate disease management. Innovative therapeutic strategies are urgently required to enhance treatment efficacy, improve patient adherence, and minimize adverse effects. Toward this, strategies involving use of drug combinations, reducing dosing frequencies, and targeting TB-infected cells are gaining attention. In my dissertation, we explored the combination therapy involving two FDA-approved anti-TB drugs, Bedaquiline (BDQ) and Pretomanid (PTD). The BDQ-PTD combination reduced minimum inhibitory concentration (MIC), compared to individual drugs and demonstrated additive/synergistic effects at 1:4 drug ratio. In addition, to improve the drug solubility and enable local delivery into the lungs (via inhalation), the drugs were encapsulated in polymeric nanoparticles (PLGA NPs) and spray-dried into dry powder particles (PLGA NPs SD; non-targeted formulation). Further, to get desired aerosolization properties of spray-dried powder, Quality-by-Design (QbD), a regulatory-based approach was employed. Prior knowledge in spray drying and risk assessment were utilized as part of the QbD approach which helped optimize the spray drying parameters. The optimized non-targeted formulation demonstrated high drug loading, biphasic drug release, long-term storage stability, and suitable aerosolization performance (MMAD 1-5 µm and FPF \u3e75%). Further, the non-targeted formulation demonstrated similar MIC in vitro and enhanced intracellular M.tb inhibition, in infection studies, compared to free drug combination. However, to facilitate active targeting of macrophages wherein TB resides, we prepared mannose-decorated PLGA NPs (Man-PLGA NPs; targeted formulation) using QbD-optimized process parameters The targeted formulation enhanced macrophage targeting via receptor-mediated endocytosis and phagocytosis in vitro and further resulted in bacterial inhibition. Lastly, a TB spheroid model was developed for in vitro screening of non-targeted and targeted formulations. The developed TB spheroid models showed uniform size distribution, high cell viability and lipid deposition, closely mimicking the physiological condition of granulomas in vitro. Targeted formulation demonstrated superior intracellular bacterial inhibition in TB spheroid model compared to free drug combination and non-targeted formulation. In summary, the potential of combination therapy, particulate-based inhaled drug delivery, and active targeting were successfully investigated to advance efficient and patient-friendly TB treatments
PHARMACOKINETIC MODELING OF METONITAZENE AND ISOTONITAZENE USING IN VITRO AND IN VIVO MODELS AND COMPARISON TO HUMAN POSTMORTEM CASEWORK
Get PDFMetonitazene and isotonitazene are two benzimidazole opioids that are contributing to the opioid crisis nationwide. Limited pharmacokinetic data has been published on these nitazene compounds, therefore this study sought to determine if these two structurally similar opioids would have comparable half-lives and clearance utilizing in vitro and in vivo models. Using the data determined in the pharmacokinetic study, and by testing human postmortem cases, this study aimed to inform interpretation of these drugs detected in human casework. Sample analysis for all aspects of the study was performed utilizing LC/MS/MS. In vitro pharmacokinetics of both drugs were examined using a human liver microsomes (HLM) model. Drug solutions at 2.5 ug/mL were incubated with HLM at 1 mg protein/mL. Metonitazene and isotonitazene showed identical rates of metabolism in this model when comparing both mean half-lives (22.6 and 21.9 min) and intrinsic clearance rates (36.5 and 37.2 mL min-1 kg-1) respectively. These half-lives were both significantly shorter than the in vivo study. Sprague Dawley rats were administered a single dose of drug intravenously at 2.5 µg/kg or intraperitoneally at 25 µg/kg. Blood and urine were collected over six hours, and brain and liver were dissected. Metonitazene (88.5 min IV and 117.5 min IP) exhibited a shorter half-life compared to isotonitazene (44.7 min IV and 56.4 min IP) in both administrations. The mean calculated volume of distribution for isotonitazene was higher than metonitazene, 59.6 mL and 37.3 mL respectively, which likely contributed to the longer half-life. In rat urine samples, two metabolites were detected. In human postmortem cases, blood levels for isotonitazene in ten cases, ranged from 0.11 – 12.0 ng/mL and metonitazene in six cases ranged from 0.10 – 1.5 ng/mL. Metonitazene was more likely to be detected in urine. All four metabolites tested were detected in human samples, therefore species differences were exhibited as compared to rats. It has been proven from in vivo studies that despite their structural similarities, metonitazene and isotonitazene show significant differences in clearance from the body. Nitazenes continue to emerge on the illicit market, and this study provides information on how this class of drugs behaves in the body
IDENTITY DENIAL AND FOOD CHOICE: DO CHINESE AMERICANS REASSERT THEIR AMERICAN IDENTITY THROUGH FOOD?
Get PDFFood choice is impacted by a variety of different factors, including cultural, social and socioeconomic (Chen & Antonelli, 2020; Contento, 2008; Rozin, 2015). Food choice has a major impact on an individual’s health, and research has shown an association between the prototypical “American diet” and an increased risk for health conditions such as hypertension, diabetes, and stroke (Liu et al., 2020). One important social factor that can influence food choice is the desire to appear as a prototypical member of a social group (Cruwys et al., 2012). For example, when an individual’s social identity is questioned (identity threat), they may be more likely to eat foods consumed by the “in-group” (Bosson et al., 2009; Guendelman et al., 2011). However, previous research investigating the role of identity threat on food choice only included Asian American college students from Washington state (Guendelman et al., 2011). The present study filled a gap in the literature by experimentally testing the impact of American identity denial on food choice in Chinese-American adults from across the U.S., the largest subgroup of Asian-Americans. Participants were randomly placed in one of two conditions – one in which American identity denial was made salient before being presented with a menu of food options and one in which food options were presented first. When participants viewed the food menu, they were asked to report their preference and their daily consumption of American and Chinese dishes. Preference and daily consumption of American versus Chinese food did not differ between the American identity denial and control conditions. However, compared to participants born in the U.S., participants who were not born in the U.S. found prototypical American food to be less appealing than prototypical Chinese food. Participants who endorsed cultural food security were also less likely to eat American food daily than Chinese food. These findings suggest that both generational status and cultural food security are important factors for food choice in the Chinese-American population, with important implications for designing health interventions targeted to this population
SYNTHESIS OF LEISHMANIA SPP ANTIGENS FOR THE DEVELOPMENT OF VACCINE CANDIDATES
No full textLeishmaniasis is a neglected tropical disease caused by the protozoan parasite of the genus Leishmania. Presently no vaccine against Leishmaniasis is available, so there is a need for new anti-leishmanial treatments, including an effective preventive vaccine. We focus on developing vaccine candidates based on leishmania’s cell surface carbohydrate antigens. Saccharides heavily envelop the cell surface of Leishmania, lipophosphoglycan (LPG) becoming a significant glycan in most leishmania species. Its intrinsic antigenicity makes this polysaccharide a useful target for developing conjugated vaccine candidates against all leishmaniasis variants. In this report, we present our progress towards the synthesis of the fragments of LPG present in Leishmania donovani, the causative agent of visceral leishmaniasis (VL) for its further utilization in the glycoconjugate vaccine candidate. Two clickable forms of Galβ(1,4)Man, mainly O-glycoside and phospho-glycoside moieties, were synthesized to facilitate their conjugation to protein carriers. These derivatives were synthesized to support subsequent investigations into immunological responses and antibody-binding properties. Moreover, capping tetrasaccharide was synthesized successfully from Galman core using orthoester strategy. To finalize the synthesis of the target Leishmania donovani LPG fragment, we linked the capping tetrasaccharide with the GalMan repeating unit via a phosphodiester bon
A MIXED METHODS ANALYSIS OF HURRICANE TRENDS AND EXPERTS’ PERCEPTION OF FUTURE MILITARY HURRICANE READINESS
Get PDFGuided by the four theories of disaster, two civil-military theories, and two communication theories, this mixed methods study was an investigation of whether hurricanes in the North Atlantic basin are increasing in frequency and whether Defense Support of Civil Authorities (DSCA) practitioners perceive the DoD is prepared to assist FEMA when the next major hurricane strikes. The DoD is a last resort with a unique and tremendous capability to support FEMA during hurricane response. To better understand hurricane trends and DoD’s hurricane response posture, this study was an analysis of 171 years of tropical cyclone data from the National Oceanic and Atmospheric Administration, followed by an evaluation of 30 DSCA professionals’ semistructured interview responses. Disagreement about the frequency of hurricanes and responses from interviews indicated the DoD is ready; however, there are a few gaps in overall readiness to address before the next response. This research is timely and significant because property damage from hurricanes is costly, with increasing death rates. A thorough study of the actual frequency of hurricanes and the feedback from DSCA experts regarding the DoD’s hurricane readiness posture offers a pathway toward efficacious disaster preparedness and response. The results of this study provide critical information for decision-makers and policymakers in the federal, state, local, tribal, and territorial governments to make sound decisions before the next major hurricane
BLACK MALES’ EXPERIENCES OF RESILIENCE: A NARRATIVE STUDY ON COLLEGE STUDENTS EXPERIENCES DURING THE COVID-19 PANDEMIC
No full textBlack men’s resilience has historically been discussed, interwoven, and disguised by deficit-based models rather than strength-based ones. The current study examined Black men\u27s resilience using a strength-based model for Black male students in higher education institutions. Specifically, the experiences and resilience of Black men before and during the COVID-19 pandemic were explored. This study targeted Black male students from an urban institution, with the aim to find out what key elements supported their resilient behavior throughout the most challenging times in their college career. The African American Male Theory and Resiliency Theory used as the theoretical framework. A narrative methodology approach was used to study 10 Black males, ages 18 and over who self-identified as Black and exemplified resilience through their grade point averages (GPA). Interviews and focus groups were conducted using a WebEx online platform to obtain the research data. The research used themes such as barriers that impacted Black males, spiritual and religious guidance and effective college resources to examine the central research question: What are Black males experiences of resilience while in college
THE TRANSPARENCY PROBLEM IN HIGHER EDUCATION ADMINISTRATION: USING A GROUNDED THEORY TO CREATE A MODEL FOR REBUILDING TRUST
Get PDFTuition-dependent higher education institutions face myriad external and internal challenges, including waning public confidence, demographic shifts, systemic sluggishness, and reduced workforces. Research on higher education administration tends to focus on senior-level leaders, with the operational experience of rank-and-file administrators largely absent from scholarly inquiry. This research endeavors to address the gaps in research by centering the experiences of entry and mid-level non-unionized administrators at tuition-dependent institutions. Guided by systems theory and using Kathy Charmaz’s Constructivist Grounded Theory methodological approach, this research presents a grounded theory of broken trust and a foundational pipeline model to mitigate this breakdown in trust and foster systemic resilience among administrators at tuition-dependent higher education institutions. If implemented, the foundational pipeline model presents an opportunity to provide essential administrative members within individual higher education institutions the ability to both weather current challenges and be prepared to successfully navigate future internal and external disruptions. By cultivating systemic resilience among higher education administrators, this research can play a role in ensuring the long-term sustainability of higher education as a larger social system
A COMPARISON OF LOW-INTENSITY CBT PROGRAMS: EVALUATING THE EFFECTS OF DESIGN ON REBT INTERVENTIONS
Get PDFLow-Intensity CBT interventions have become more popular over the years due to the expanding use of the internet and technology. A particular subset of Low-Intensity CBT, phone-based apps, have become more available on app-stores. The research literature on phone-based apps has not kept up in pace in comparison to the development of new applications. This leaves the quality and efficacy of such apps to be left untested. Furthermore, most applications are dominated by a Beck’s Cognitive Therapy (CT) approach, with more Dialectical Behavior Therapy (DBT) apps on the horizon. Rational Emotive Behavior Therapy (REBT) has been largely neglected within the app-based domain. Our study takes on the development of an REBT based phone app and takes a look at mental health outcomes from using other established apps in the CT and REBT space. An experimental phone app, REBT Guide to Emotions, was developed for this study. WoeBot was used as a CT app control group and PsyPills was used as an REBT app control group. Participants were asked to utilize one of three phone apps and report on their pre and post mental health measures utilizing the OQ-45.2. Participants in all groups did not see any significant changes in their total OQ scores, while WoeBot did demonstrate an improvement in short-term negative mental health symptoms. Other research conducted on the apps points to there being a connection between reminders, app engagement, and user outcomes
“1000 ACRES OF RESTRICTED LAND”: THE LARGER IMPLICATIONS OF ROLAND PARK ON BALTIMORE, FROM 1891 TO THE PRESENT
Get PDFThis study addresses the circumstances that led to and the long-term consequences of racially exclusive suburban developments in Baltimore City during the nineteenth and twentieth centuries. In 1891, British investors and urban planners joined together to build the Roland Park District, one of the nation’s first planned suburban neighborhoods to include a racially restrictive covenant. Ideally located on the Chesapeake Bay, Baltimore developed a high-functioning port, which in turn supported westward expansion, progress, industrialization, and immigration. Located just north of Baltimore’s 1888 city limits, which would later expand to absorb Roland Park in 1918, Roland Park was built as an upper-class streetcar suburb. Inspired by the rise of the garden city movement and similar planned suburbs like Riverside, Illinois, the Roland Park Company intended their development to capture the desired ideals of nature, beauty, and luxury without sacrificing proximity to urban centers. Gaining an understanding of the rationale, profitability, and social circles of the Roland Park Company developers captures the motivation behind the long-lasting consequences of the development. This thesis aims to analyze the foundation laid and the precedent set by the Roland Park Company in Baltimore by investigating the historical beginnings of Baltimore, the Roland Park Company Records Collection, City of Baltimore infrastructure records, the works of urban planners including Ebenezer Howard, Frederick Law Olmsted Sr., and Frederick Law Olmsted Jr., Civil Rights Laws, and formalized housing policies. Furthermore, in a city with a large African-American population, the Black communities in Baltimore suffered from the institutionalization and spread of housing policies based on race and class that emerged following the garden suburb developments. While the Roland Park District only occupied a few square miles of Baltimore City, it dramatically deepened racial, class, and wealth divides in the city and across the nation due to its successful exclusionary practices