The University of Maryland Graduate School Baltimore (UMGSB) offers 27 master's and doctoral programs in health, physical, biomedical, medical, and social sciences.

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  • Pharmacometabolomics of clopidogrel: Determining the genetic and metabolic contributors to clopidogrel response

    Bromberek, Sarah Katherine; Beitelshees, Amber L. (2021)
    Clopidogrel is a commonly prescribed antiplatelet drug and there is considerable variability in response. The PAPI study was conducted in 687 individuals to determine the genetic predictors of clopidogrel response. Targeted metabolomic profiling of 42 amines was performed in a subset of 198 PAPI subjects with genetics data available. We identified the metabolic signature of clopidogrel and determined metabolites associated with clopidogrel-induced changes in platelet reactivity. We found tyrosine was most significantly changed after exposure to clopidogrel, and BCAAs baseline levels were associated with clopidogrel-induced changes in platelet aggregation. Gaining insights into factors that influence variability in antiplatelet response is important for identifying novel antiplatelet mechanisms or biomarkers for predicting response. These findings can have long-term implications toward advancing precision medicine in antiplatelet therapy.
  • Understanding Financial Behavioral Health and Race (Racism), and their Association with Investment Risk Willingness

    Anvari-Clark, Jeffrey; Frey, Jodi J; 0000-0003-3234-8549 (2022)
    The conception of financial behavioral health (FBH) is new and lacks a common definition. This dissertation frames FBH as being comprised of financial precarity, financial self-efficacy (FSE), and financial well-being, and has the potential to influence multiple other behavioral health domains. The literature review shows how each component of FBH relates to other domains of behavioral health, including mental health, physical health, coping health, and social health. Stress and life course theory and insights on scarcity from the behavioral sciences are used to understand how FBH impacts the human condition, which, in a negative context, can manifest as money disorders. To explore FBH empirically, data from the 2018 National Financial Capability Study (N = 27,091; FINRA Investor Education Foundation, 2018) was used. First, a measure of financial precarity was constructed with both objective and subjective components, using exploratory and confirmatory factor analyses, and achieved adequate fit. Next, the relationship between FBH and its component parts was assessed, again with adequate fit. The study attempted to determine how a subset of Black and White survey respondents experienced FBH differently, according to collectivist or individualist financial values orientations. However, it was found through measurement invariance testing that although the FBH model had an excellent fit for White respondent data, it poorly fit the data from Black respondents. Due to the model variance, determining further impact of racial group affiliation on the outcome could not be conducted. The study concluded with a structural equation modeling analysis and determined that, controlling for key demographic variables, FBH accounted for 37% of the variance in investment risk willingness (R2 = .368; β = 0.256, p < .001). The project contributes a new measure of financial precarity and a basis for FBH. The variance between the sub-groups may indicate that the survey questions are inadequately capturing the collectivist experience by which many people treat their finances. The project shows how finances can have a psycho-behavioral impact on well-being and decisions, the influence FBH has on investment risk willingness, and suggests that low FBH may perpetuate wealth gaps.
  • Time-Use and Well-Being in Family and Other Unpaid Caregivers of Older Adults

    Baik, Sol; Lehning, Amanda J.; 0000-0002-5081-4956 (2022)
    Due to the intensive time commitment for caregiving, caregivers report limited freedom to engage with others, participate in physical activities, pursue leisure activities, and have adequate time for sleep. Few studies have focused on caregivers’ time-use across different activities, particularly how different patterns of time-use are associated with well-being. This study aimed to: (1) identify time-use profiles of family caregivers of older adults, (2) examine associations between identified time-use profiles and caregiver well-being, and (3) assess whether the effects of gender and race on caregiver well-being vary by the identified time-use profiles. I analyzed 1,640 family caregivers of community-dwelling older adults by combining secondary data from Round 7 (2017) of the National Study of Caregiving and the National Health and Aging Trends Study. I conducted latent profile analysis to estimate time-use profiles including covariates and outcomes. Three classes of caregivers emerged based on time-use patterns. The High Committed class (20%) spent the longest time in non-eldercare related committed activities, such as household activities and paid work. The High Discretionary class (49%) spent the highest amount of discretionary time, including social activities, physical activities, and other free-time activities. They also spent the least amount of non-eldercare committed time compared to the other two caregiver types. Lastly, the Balanced class (31%) allocated time relatively evenly in all activities. When comparing well-being outcomes between time-use profiles, caregivers in the High Discretionary class had worse self-rated health but lower levels of anxiety than the Balanced class. This study also found significant gender differences in depression, which varied by time-use profiles. Research on time-use and caregiver well-being may help identify at-risk caregiver groups based on lifestyle profiles and develop targeted policies to promote better caregiver well-being.
  • Investigating the Role of Acetylated Tubulin on Microtubule Dependent Mechanotransduction in Striated Muscle

    Coleman, Andrew; Ward, Christopher, Ph.D.; Lederer, W. Jonathan (2022)
    Mechanotransduction is critical to the maintenance and development of striated muscle in response to a change in workload. Mechanical sensors within muscle respond to muscle movement to regulate EC coupling, gene expression, and signal propagation. Our lab has investigated the role of the cytoskeleton as a mechanosensor in striated muscle. Biophysical properties of microtubules (MTs) allow for mechanical energy created during sarcomere shortening to be transferred to the cytoskeleton network and associated proteins. Upon contraction or stretch, mechanical energy is transferred through the MT network to the membrane bound NADPH oxidase 2 (Nox2) to trigger a localized increase in reactive oxygen species (ROS) production that regulates calcium channels at the triad junction. This mechanotransduction pathway is regulated not only by the abundance of MT and Nox2, but also the biophysical properties of MTs. Post translational modifications to tubulin have various consequences to polymerized tubulin and create distinct subsets of MT populations within muscle. While MT acetylation of lysine 40 within the lumen of polymerized MTs is abundant in muscle, little is known about its function in muscle. Recent investigations that explored the biophysical properties of MT acetylation in vitro have shown that acetylation increases the resistance of MTs to damage by repeated mechanical insults. Here we sought to investigate the role of MT acetylation in muscle mechanotransduction in health and disease. Using Pharmacologic and genetic strategies, we show that microtubules enriched in acetylated α-tubulin increase cytoskeletal stiffness and viscoelastic resistance. These changes slow rates of contraction and relaxation during unloaded contraction and increased activation oof Nox2 by mechanotransduction. Importantly, MT acetylation had no effect on tension produced during contraction of intact muscle enabling enhanced mechanotransduction without altering force production. Furthermore, we show that microtubule PTMs are elevated in heart failure, muscular dystrophy, and aging. These changes translated to excess mechanotransduction and are potential therapeutic targets to diminish oxidative stress associated with muscle disease. Together, these findings add to growing evidence that microtubules contribute to the mechanobiology of striated muscle and are detrimental muscle disease modifiers.
  • The Evolution of B Cell Selection and Affinity Maturation in Cartilaginous Fishes

    Matz, Hanover Christian; Dooley, Helen, Ph.D.; 0000-0002-0669-1696 (2022)
    Affinity maturation of the B cell immunoglobulin (Ig) repertoire occurs through coordinated somatic hypermutation (SHM) and Darwinian selection of clones in specialized microanatomical structures known as germinal centers (GCs). GCs have only been identified in the endothermic vertebrates, and so it was long presumed that the antigen (Ag)-specific Ig responses of ectothermic vertebrate lineages were “primitive”. However, affinity maturation and immunological memory have subsequently been demonstrated for the oldest extant vertebrate class with Ig-based adaptive immunity, the cartilaginous fishes (Chondrichthyes). In this dissertation, I investigated the cellular model of B cell selection in the nurse shark (Ginglymostoma cirratum) spleen and determined how it influences the dynamics of the Ig repertoire. I found that shark splenic B cell follicles possess many functional analogs of mammalian GCs: (1) segregation of SHM and selection regions by CXCR4/CXCR5 expression in B cells, (2) functional T follicular helper-like cells, (3) presentation of nondegraded Ag, and (4) Ag-driven selection of mutated Ig clones. I also demonstrated that the transcription factor BCL6 likely regulates the shark B cell response. Through a long-term immunization study, I demonstrated that this selection model can generate IgNAR repertoires that are both diverse and of high affinity. In multiple animals immunized by the same methods, I observed uncoupling of the T-dependent isotypes, IgNAR and monomeric IgM. Sharks that produced robust IgNAR titers matured their polyclonal repertoires to subnanomolar binding affinities and generated a diverse pool of memory clones. Together, this suggests that B cell selection in cartilaginous fishes evolved to support both affinity maturation and Ig repertoire diversification, possibly utilizing SHM to anticipate future pathogen variants. Finally, I developed a method of magnetic nanoparticle enrichment to isolate Ag-specific B cell clones directly from the peripheral blood of sharks. Overall, the data presented in this dissertation indicate that all the fundamental components of B cell selection were present at the advent of adaptive immunity in jawed vertebrates. Furthermore, these components were capable of affinity maturation of the B cell repertoire without sacrificing receptor diversity. My findings have many implications for our understanding of the evolution of the B cell response in vertebrate lineages.
  • The Role of CCAAT/Enhancer Binding Protein (C/EBP) Homologous Protein (CHOP) in the Antileukemic Activity of Artemisinins

    Tabassum, Sumiya; Civin, Curt I.; 0000-0002-2086-9737 (2022)
    Current chemotherapy options for acute myeloid leukemia (AML) are still limited, despite recent efforts to develop novel drugs for AML with greater efficacy and acceptable toxicity. Several antimalarial analogs of the compound artemisinin (ARTs) possess antineoplastic activity across many cancer cell types, with highest potency against leukemia cells, but their detailed molecular mechanisms of action (MOA) are inconclusively established. This study leveraged our previous findings that ARTs downregulated the antiapoptotic protein, myeloid cell leukemia-1 (MCL1), and upregulated the transcription factor, CCATT/enhancer-binding protein homologous protein (CHOP), in human AML cells. We assessed the roles of these molecules in the antileukemic MOA of the highly potent ART analog, ART838, in the human MOLM14 AML cell line. We found that enforced MCL1 overexpression rescues from ART838-mediated cell death. However, neither CHOP overexpression nor CRISPR-Cas9-mediated CHOP knockout affected growth/survival or cellular levels of MCL1 protein, in the absence or presence of ART838.
  • Disynaptic Prefrontal Cortical Input to the Dorsolateral Striatum

    Harris, Morgan; Mathur, Brian N. (Brian Neil); 0000-0002-8424-7822 (2022)
    The dorsomedial striatum (DMS) is responsible for actions that are reversible, goal-directed, and require attentional oversight. In contrast, the dorsolateral striatum (DLS) is responsible for relatively irreversible, but precise habitual actions that need little attentional oversight. In addiction, the balance between these two action strategies is shifted toward habits, leading to compulsive behaviors. The DMS is activated by input from executive, prefrontal cortical areas of the brain, while the DLS is activated by sensorimotor cortices. A major gap in knowledge is how executive cortical centers may mediate shifts away from habitually performed actions. While no executive cortical areas monosynaptically activate the DLS, we hypothesize the existence of disynaptic circuits allowing executive cortical control of the DLS. To test this, we utilized trans-synaptic target specific tracing (TranSTart) to reveal that executive cortices disynaptically project to the DLS through the basolateral amygdala (BLA) and the rostral intralaminar nuclei of the thalamus (rILN).
  • Generational Perspectives of Orthodontists in the U.S. and Canada– A Survey Study

    Hussain, Syed Rassal; Bosio, Jose A. (2022)
    Objective: To identify differences between generations of orthodontists in the U.S. and Canada and to evaluate the perspective of each generation on widely debated topics in orthodontics. Materials and Methods: A 22-item IRB approved survey was distributed to orthodontists in the U.S. and Canada. Participants were asked questions about the use of technology, future of clear aligner therapy (CAT), orthodontic education, student debt, marketing, and corporate orthodontics among other topics. Results: Significant increase in female orthodontists over generations and a decrease in orthodontic educators was found (P<0.001). Among generations, differences were found in regard to their amount of student debt, use of specific diagnostic tools, marketing preferences, and their opinion on the future of CAT. Conclusions: Clear distinctions exist between different generations of orthodontists. Issues such as increasing student debt load and a decrease in orthodontic educators over generations should be addressed to preserve the future of the orthodontic profession.
  • Design, Development, and Characterization of Gallium (III) Salophen Metallotherapeutics Targeting Heme Sensing and Iron Acquisition Pathways in Pseudomonas aeruginosa

    Centola, Garrick; Wilks, Angela; Xue, Fengtian, Ph.D.; 0000-0001-5965-9545 (2022)
    The development of new antibiotics is outpaced by the rise in multi-drug resistant (MDR) bacteria, creating a global health problem. Pseudomonas aeruginosa, one such bacterium, is labeled as a “critical priority” pathogen by the WHO for its resistance to treatment and prevalence in hospital-acquired infections and immunocompromised patients where it is often life threatening. Adding to this problem, most new discoveries are derivatives of existing antibiotic classes rather than new strategies. Newer approaches targeting bacterial pathways critical to infection but not survival outside the host are expected to exert less selective pressure and slow resistance onset. One such strategy is interfering with bacterial iron uptake and utilization, as iron is a key micronutrient with several iron-regulated virulence traits used to counter iron-sequestering defense mechanisms of the host. P. aeruginosa can shift between the acquisition of labile iron stores and the more abundant heme-bound iron at various stages of infection, so inhibitors targeting these pathways must account for this adaptability. One such approach to targeting iron utilization in several forms is the use of gallium, which mimics ferric iron in ionic size and charge but cannot undergo critical redox processes, thus causing toxicity in the bacteria that acquire it under the guise of iron. This work describes the synthesis and characterization of Gallium Salophen (GaSal) and subsequent analogs targeting heme and iron acquisition pathways in P. aeruginosa. In this characterization, GaSal binds to a hemophore, HasAp, secreted by P. aeruginosa, and inhibits an extra-cytoplasmic function (ECF) signaling cascade with the outer-membrane receptor HasR, which is critical for sensing and adapting to host heme levels. GaSal is simultaneously a substrate for uptake, independent of its effect on HasAp. Using a combination of cell-based assays as well as in vitro target characterization and finally preliminary animal infection studies, GaSal and subsequent derivatives are shown to be promising new developments targeting several points in the iron uptake and utilization pathways of P. aeruginosa. Continued developments aim to retain such activity and include several routes towards further optimization and development as a therapeutic.
  • Associations of Rare Variants Underlying Depressive Symptoms in the Old Order Amish Founder Population

    Choe, Jayme Hyowon; Ament, Seth A.; 0000-0003-3453-8944 (2022)
    Depressive disorders are among the leading causes of disability worldwide. Genome-wide association studies of common variants of depressive disorders have identified 178 risk loci, yet mechanisms remain elusive due to the very small effects of common variants. Certain rare variants may have larger effects, but exome and genome sequencing studies to date have been underpowered to detect effects of specific rare variants. One approach to address these limitations is to utilize population isolates, like the Old Order Amish (OOA), in which certain rare variants become enriched due to the population bottleneck effect. This study aimed to identify rare variants associated with depressive symptoms, utilizing whole exome sequencing (WES) and phenotypic data from two OOA cohorts (N = 5,052), the Amish Wellness Study and the Amish Connectome Project. We identified five significant SNP-depressive symptoms associations. Case-series phenotyping revealed high depressive symptoms screening scores across carriers of each variant compared to non-carriers.
  • Identifying targets of sulforaphane in mesothelioma

    Ezeka, Geraldine; Eckert, Richard (Richard L.); 0000-0002-9222-0566 (2022)
    Mesothelioma is a fatal cancer of the mesothelial lining that is caused by asbestos exposure. The most common forms of mesothelioma arise in the pleural and peritoneal cavities of the lung and abdomen. Current treatment involves surgical resection and chemotherapy, but this approach is marginally successful and leads to drug resistant disease. We study sulforaphane (SFN), a nature derived anti-cancer agent that has high bioavailability and low toxicity. Our goal is to identify sulforaphane responsive targets in mesothelioma. Protein arginine methyltransferase 5 (PRMT5) is an epigenetic modifier that acts with methylosome protein 50 (MEP50) to symmetrically dimethylate arginine residues on histones H3 and H4 to silence target gene expression. PRMT5/MEP50 histone methylation has been implicated in cancer and is associated with silencing of tumor suppressors leading to enhanced cancer development. Our studies show that PRMT5/MEP50 knockdown reduces H4R3me2s and attenuates the cancer phenotype. Moreover, SFN reduces PRMT5/MEP50 function and cancer cell proliferation, spheroid formation, invasion and migration. Further, forced expression of PRMT5/MEP50 antagonizes SFN suppression of the cancer phenotype, suggesting that loss of PRMT5/MEP50 is required for SFN action. SFN suppression of mesothelioma tumor formation is associated with reduced PRMT5/MEP50 levels and activity. These findings suggest that SFN treatment suppresses PRMT5/MEP50 activity to attenuate the cancer phenotype. We also examined SFN impact on AKT/mTOR and MEK/ERK1/2 signaling which act together to activate translation of selected mRNA species via regulation of the eIF4F complex. AKT/mTOR activity leads to 4E-BP1 phosphorylation, leading to the release of eIF4E, which binds to eIF4G to assemble the eIF4F complex. MEK/ERK1/2 signaling activates MNK1/2 which activates eIF4E in the eIF4F complex. These events result in a selective increase in the translation of a subset of mRNAs. We show that SFN treatment suppresses AKT/mTOR activity leading to reduced phosphorylation of 4E-BP1 which would be expected to reduce assembly of the eIF4F complex. However, we also observe an unexpected increase in MEK/ERK1/2 activity and MNK1/2 phosphorylation which we propose is a compensatory response to the inhibition of activity of the eIF4F complex. These findings suggest that SFN may suppress eIF4E-dependent translation to attenuate the mesothelioma cancer phenotype.
  • Impact of mobile elements on human traits and diseases

    Chuang, Nelson Ta-Ching; Devine, Scott E.; 0000-0002-2015-8935 (2022)
    Several large-scale Illumina whole genome sequencing (WGS) and whole exome sequencing (WES) projects have emerged recently that have provided exceptional opportunities to discover mobile element insertions (MEIs) and study the impact of these MEIs on human genomes. However, these projects also have presented major challenges with respect to the scalability and computational costs associated with performing MEI discovery on tens or even hundreds of thousands of samples. To meet these challenges, we have developed a more efficient and scalable version of our Mobile Element Locator Tool (MELT) called CloudMELT. We then used MELT and CloudMELT to perform MEI discovery in 57,919 human genomes and exomes, leading to the discovery of 104,350 non-redundant MEIs. We leveraged this collection: 1) to examine the population distributions and subfamilies of these MEIs, 2) to examine the mutagenesis of GENCODE genes, ENCODE-annotated features, and disease genes by these MEIs, and 3) to examine the potentially active L1 source elements that drive mobilization of new Alu, L1, and SVA MEIs in humans. Our study provides new insights on the L1 source elements that drive MEI mutagenesis and brings forth a better understanding of how this mutagenesis impacts human genomes.
  • An Evaluation of the Effectiveness of Extended-Release Naltrexone

    Hochheimer, Martin; Sacco, Paul; Unick, George Jay; 0000-0001-6644-4841 (2022)
    Medications for the treatment of opioid use disorder (MOUDs) are considered the gold standard form of treatment for this condition. There are two forms of MOUD treatment, agonist, and antagonist. Agonist treatment has the medical system provide people with opioid use disorder methadone or buprenorphine which are long lasting opioids that do not produce a euphoric reaction with the goal of alleviating cravings and mitigating illicit use of opioids. Conversely, antagonist treatment blocks opioid absorption in the brain. Extended-release naltrexone (XR-NTX) is the most common antagonist treatment it is administered as a once-monthly injection. During the month after injection, patients who use opioids will not experience their effect and by negating the reward of opioid use the treatment discourages continued use. This study evaluated the effectiveness of buprenorphine and XR-NTX treatment on three characteristics: treatment retention, risk of opioid related acute care incidents, and changes in healthcare costs during treatment. Data from the Truven Health MarketScan® databases which records the date, type of interaction, and cost of every interaction that a person insured privately with one of over 250 insurance providers has with the healthcare system was used to identify a sample of approximately 30,000 people who were treated with buprenorphine or and 617 who were treated with XR-NTX for opioid use disorder. Treatment episodes were constructed based on filled prescription information and a frailty model survival analysis was fit both to a matched sample and the whole sample to length of treatment for each medication. The risk of acute care incidents was evaluated using a generalized estimating equation, and healthcare costs were evaluated using fixed-effects regression models. The study found that there are no significant differences in treatment retention between the MOUDS. Treatment with either medication was associated with an approximately 10% reduction, per day in treatment, of the odds of experiencing an acute care incident during one month. Healthcare costs increased while people were in treatment, with either MOUD, between approximately 0.85% and 1.5% for both opioid related and non-opioid related services.
  • The role of Angiopoietin-like 4 in head and neck squamous cell carcinoma progression and dissemination

    Hefni, Eman; Montaner, Silvia (2022)
    Dysregulation of cellular signaling is instrumental in the promotion of tumor cell metabolism, proliferation, tissue invasion and metastasis. Molecular-based therapies for neoplastic diseases are designed to modulate or interact with cell surface receptors, intracellular cascades, or microenvironment components related to the extracellular matrix, tumor vasculature and immune response. To design these therapies, an improved understanding of the molecular underpinnings leading to tumor growth is essential. The overall aim of our investigation is identification of the molecular mechanisms associated with the induction of tumor cell migration and proliferation induced by Angiopoietin-like 4 (ANGPTL4), a pro-tumorigenic and pro-angiogenic factor, in head and neck cancer squamous cell carcinoma (HNSCC). HNSCC accounts for around 54,000 new cases and 11,000 deaths per year in the United States. Unfortunately, the clinical management of this tumor remains challenging. Our studies, divided into two research aims, use in vitro cell-based models together with signal transduction and cell and molecular biology methods. Our results demonstrate that: 1) ANGPTL4 is upregulated in human-derived dysplastic oral keratinocytes (DOKs) and HNSCC cell lines, but not in normal oral keratinocytes (NOKs), suggesting an early and sustained role for ANGPTL4 in disease progression. ANGPTL4 is a molecular marker in biopsies from patients with mild-moderate or moderate oral epithelial dysplasia, primary HNSCC and metastatic HNSCC. ANGPTL4 is necessary and sufficient to promote cell migration in DOKs and HNSCCs lines. Binding of ANGPTL4 to neuropilin-1 (NRP1) leads to paxillin (PXN) phosphorylation and cell migration in an ABL1-dependent manner, exposing the ANGPTL4/NRP1/ABL1/PXN cascade as a vulnerable target for HNSCC treatment. 2) Epidermal Growth Factor (EGF)- and Hypoxia-inducible Factor-1 (HIF-1)-mediated pathways cooperate in the upregulation of ANGPTL4 in normal and dysplastic oral keratinocytes and HNSCC cells. Besides EGF, the EGF ligand amphiregulin leads to an increase in ANGPTL4 and is upregulated in HNSCC lesions. ANGPTL4 activates the HNSCC molecular markers p38 MAPK, AKT and mTOR in NOKs; these kinases may act as potential intracellular regulators of the autocrine signals and paracrine secretions that ANGPTL4 activates to promote HNSCC tumorigenesis. Collectively, our findings suggest that ANGPTL4 and its associated signaling molecules are potential therapeutic targets in HNSCC clinical management.
  • Impact of Undertreatment of Depression on Suicide and Suicide Attempt among Children and Adolescents: A Simulation Study with Microsimulation and Agent-Based Models

    Zhang, Chengchen; dosReis, Susan; 0000-0003-3349-8725 (2022)
    Background: Depression is a strong risk factor for suicide, but undertreatment of depression is common among children and adolescents. The impact of undertreatment of depression on suicidal behaviors in this population is largely unknown due to the limitations of conventional data sources and methods. This dissertation research aims to overcome these challenges by using simulation models to answer two questions: 1) Is undertreatment of depression associated with increased risk of suicidal behaviors? 2) Do interventions that reduce undertreatment of depression lower the risk of suicidal behaviors? Methods: A microsimulation model simulated the 1-year suicide rate and suicide attempt risk with 12-, 36-, 52-week antidepressant treatment and no treatment in children and adolescents with depression. Modified Poisson regression estimated the suicide rate ratios and suicide attempt risk ratios for 12-, 36- and 52-week treatment compared with no treatment. An agent-based model simulated the potential impact of the following interventions in preventing suicide and suicide attempt in a synthetic population of children and adolescents: 1) depression screening (i.e. reducing untreated depression); 2) reducing attrition during depression treatment (i.e., increasing the proportion who complete the first 12 weeks of treatment); 3) suicide intervention (i.e., screen and treat individuals who need suicide care) among depressed individuals; 4) universal suicide intervention in medical settings. Results: Compared with no treatment, 12-, 36- and 52-week antidepressant treatment was significantly associated with decreased suicide rate and risk of suicide attempt. Depression screening could reduce the risk of suicide attempt (-0.64% (95% Credible Interval (CI): -1.13%, -0.11%)) only when 80% untreated depression was reduced. Universal suicide intervention showed a significant decrease in the risk of suicide attempt, which increased with the screened proportion (20%: -0.68% (95% CI: -0.87%, -0.55%), 50%: -1.47% (95% CI: -1.61%, -1.77%), 80%: -2.89% (95% CI: -4.57%, -2.31%). The other interventions did not show a significant effect in reducing the risk of suicide attempt in the population. Conclusion: Antidepressant treatment for at least 12 weeks may reduce risk of suicidal behaviors. Universal suicide intervention in medical care settings may be more effective in reducing suicidal behaviors compared with interventions that reduce undertreatment of depression.
  • Global Temporary Anchorage Device (TAD) Usage: A Survey of Orthodontists

    Ashton, Kelsea; Bosio, Jose A.; 0000-0002-8045-3370 (2022)
    Objective: We aim to determine how often TADs are used worldwide and establish guidelines for implementing TADs in everyday practice. Methods: A 19 question survey was sent to orthodontists around the world asking opinion based, case-specific, and placement technique questions regarding TADs. The country of practice and length of time practicing orthodontics were the independent variables. Results: Most orthodontists use TADs rarely/sporadically. There were significant findings for how TADs are being used, sizes, and placement techniques amongst different continents. There was a significant difference in how many TADs orthodontists placed in residency according to how long they have been practicing, but it did not greatly affect frequency of use, mechanics, or placement technique. Conclusion: The frequency of TAD use is similar worldwide and amongst different age groups. Although significant data was found in this study, there is such variability in regard to TADs that clear guidelines were not established.
  • Optimal Antero-Posterior Position of the Maxillary Central Incisors and its Relationship to the Forehead in Adult African American Males

    Endres, Elise Tigani; Sanchez, Dina (2022)
    Objective: To determine an optimal antero-posterior (AP) position of the maxillary central incisors (CI) and its relationship to the forehead in African American males. Methods: 95 smiling profile photographs were taken, evaluated by orthodontists and laypersons, and categorized in Group B, R or F. The CI position and forehead inclination (FI) were measured relative to glabella vertical (GV). Statistical analysis evaluated the relationship between CI position and FI, differences between groups, and differences between orthodontists and laypersons. Results: Optimal CI position was -2.1mm behind GV. There were no significant differences between orthodontists and laypersons. All group comparisons were significantly different, except Group B v Group R. The optimal CI position relative to GV and FI were not significantly correlated. Conclusions: The AP position of the CI relative to the forehead in African American males can be evaluated to determine the optimal AP position of the CI and optimal esthetics.
  • The Perspectives of Middle Atlantic Society Orthodontists on COVID-19

    Vumback, Matthew; Schneider, Monica, D.D.S, M.S. (2022)
    Purpose: This study aims to survey Middle Atlantic Society Orthodontists on how COVID-19 has impacted and altered their practices and outlook on the profession. Methods: This cross-sectional study was designed using Qualtrics XM and consisted of 20 questions focusing on the licensed orthodontists in the MASO regions. Results: Responders had split feelings regarding the length of time out of practice due to regulations. Nearly 48% felt that it was too long, while about 49% felt that it was appropriate. During this time, over 32% have offered more aligner therapy but roughly 51% have seen a reduction in patients. Regardless, over 61% do not believe retirement plans have been affected. Conclusion: A meaningful difference in perspectives exists amongst MASO orthodontists regarding COVID-19 regulations and infection control. Treatment philosophy appears to be shifting towards clear aligner therapy and tele-dentistry. Despite the disruption to the profession, most orthodontists feel hopeful for the future.
  • A Novel Magnetic Nanoparticle Containing Adhesive to Enhance Microtensile Bond Strength of Composite Resin to Dentin: An in vivo Study.

    Bulloch, Brandon; Masri, Radi, 1975- (2022)
    Purpose: An in vivo study to compare microtensile bond strength and resin tag density of a novel adhesive that relies on magnetic force. Materials and Methods: Twenty-five teeth were obtained from subjects. In the experimental group, teeth were restored with a novel nanoparticle adhesive and magnetic force (n=16). In the control group (n=9), no nanoparticle or magnetic force was used. Teeth were extracted and cut into beams. Microtensile bond strength and resin tag density were measured. A two tailed student t test was used to compare groups. P<0.05 was considered significant. Results: There was a significant increase of microtensile bond strength of the experimental group compared to controls (P= 0.025). The SEM images showed resin tag density was increased by a magnitude of two with the experimental group. Conclusion: Magnetic force improves the microtensile bond strength and resin tag density of resin adhesive when used in vivo.
  • Characterization of filarial parasite evolution through genome assembly and transcriptomic analysis of Brugia malayi and Brugia pahangi

    Mattick, John Stocker Antalis; Dunning Hotopp, Julie C.; 0000-0002-8743-1158 (2022)
    To study the chromosomal structure of filarial parasites, the genomes of Brugia malayi and Brugia pahangi were assembled using a combination of Illumina, PacBio and Oxford Nanopore sequencing. The assembly was able to reconstruct all of the major chromosomes, including the X chromosome, which comprised over 20% of the genome in both species. Male specific sequencing was used to identify contigs associated with the Y chromosome of B. malayi, and showed that these contigs contained the majority of the repetitive sequences in the genome. A chromosomal fusion of the sex chromosomes of these species that created a pseudoautosomal region of the X chromosome and a haploid region in males was also identified. Analysis of other filarial parasites revealed that while not all species had the same fusion, this haploid region was consistently conserved. In order to compare the chromosomes of these filarial species to other species whose genomes had not been assembled into chromosome form, a classification system called Nigon elements was created to assign large conserved syntenic blocks to specific Nigon elements that were comparable across species. A large reduction in nucleotide diversity across this region of the sex chromosome was also identified, indicating that the fusions were recent. Finally, short read transcriptomics identified novel microRNAs in B. malayi that originate from both the parasite and its Wolbachia endosymbiont. Target prediction across the mammalian portion of the parasite life cycle revealed seven major clusters of co-regulated genes, including a number of developmental and adult-specific gene pathways. Furthermore, in situ hybridization imaging confirmed that the microRNAs predicted to originate from the Wolbachia were not present in the parasite nuclei, suggesting that these sequences are bacterial in origin. These findings reveal a new co-evolving pathway for endosymbiont and parasite communication.

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