Digital Commons Network^™

Influence Of Muscle Strength On Mobility In Critically Ill Adult Patients On Mechanical Ventilation, Audrey R. Roberson

Theses and Dissertations

Patients in the intensive care unit (ICU) setting are prone to develop muscle weakness and the causes are multi-factorial. Muscle strength in adult, critically ill patients on mechanical ventilation decreases with immobility. The influence of muscle strength on different muscle groups and its influence on progressive mobility in the adult, critically ill patient on mechanical ventilation has not been examined. Identifying muscle strength in this patient population can benefit overall muscle health and minimize muscle deconditioning through a progressive mobility plan. The objective of this dissertation was to describe muscle strength in different muscle groups and to describe the influence …

Age-Dependent Changes In Oxygen Supply And Demand Of Rat Spinotrapezius Muscle, Sami C. Dodhy

Theses and Dissertations

Because of the aerobic nature of cellular metabolism in mammalian organisms, a continuous supply of oxygen is necessary to maintain normal physiological function. As organisms age, their metabolic rates generally decline and there are accompanying alterations in the structure and function of the microcirculation, as this part of the cardiovascular system is especially important for oxygen exchange. The overall Oxygen Transport System can be considered as being composed of two complementary components: one for Oxygen Demand and one for Oxygen Supply. The purpose of the current work is to describe the age-dependent changes in both oxygen demand and oxygen supply …

Snd1-Targeted Gene Therapy For Hepatocellular Carcinoma, Bryan D. Mckiver

Theses and Dissertations

Staphylococcal nuclease and tudor-domain containing 1 (SND1) is an oncogene for a wide variety of cancers, including hepatocellular carcinoma (HCC). SND1 is a multifunctional protein regulating gene expression of proto-oncogenes and tumor suppressor genes, making SND1 a prime target for developing cancer therapeutics. This notion is especially attributed to HCC as most patients are diagnosed in advanced stages and the therapeutic options available for these patients are severely limited. In this study, we evaluated the therapeutic potential of a replication-defective adenovirus vector delivering SND1 shRNA (Ad.SND1sh) to human HCC cell lines, HepG3, HuH-7, and Hep3B. Adenovirus infection in HCC cells …

Structured Poetic Expressions For Emerging Adults Experiencing Bereavement, Kelcie D. Willis

Theses and Dissertations

Previous research has produced heterogeneous findings regarding the effectiveness of expressive writing in reducing grief symptomatology among the bereaved (e.g., Collison, 2016; Lichtenthal & Cruess, 2010; Stroebe et al., 2006). The purpose of this study was to address these mixed results by exploring the effects and linguistic characteristics of a novel writing task (i.e., the acrostic poem) among bereaved undergraduates, using an innovative data analysis technique (i.e., Linguistic Inquiry and Word Count). The current study recruited 68 undergraduates who had lost a loved one. Participants were randomly assigned to write over multiple days using the acrostic poem, emotional disclosure prompt, …

Evaluating And Reducing The Effects Of Misclassification In A Sequential Multiple Assignment Randomized Trial (Smart), Jun He

Theses and Dissertations

SMART designs tailor individual treatment by re-randomizing patients to subsequent therapies based on their response to initial treatment. However, the classification of patients being responders/non-responders could be inaccurate and thus lead to inappropriate treatment assignment. In a two-step SMART design, by assuming equal randomization, and equal variances of misclassified patients and correctly classified patients, we evaluated misclassification effects on mean, variance, and type I error/ power of single sequential treatment outcome (SST), dynamic treatment outcome (DTRs), and overall outcome. The results showed that misclassification could introduce bias to estimates of treatment effect in all types of outcome. Though the magnitude …

The Role Of Adam10 And Adam17 In Humoral And Type 2 Immunity, Joseph C. Lownik

Theses and Dissertations

The proper regulation of inducible costimulator (ICOS) and its ligand (ICOSL) have been shown to be essential for maintaining immune homeostasis. Loss of either protein results in defective humoral immunity, and overexpression of ICOS results in aberrant antibody production resembling lupus. How ICOSL is regulated in response to ICOS interaction is still unclear. We demonstrate that ADAM10 is the primary physiological sheddase of ICOSL in both mouse and human. Using an in vivo system in which ADAM10 is deleted only on B cells (ADAM10^B-/-), elevated levels of ICOSL were seen. This increase is also seen when ADAM10 is …

Signaling Through Homomeric And Heteromeric Cannabinoid Cb1 Receptors, Guoqing Xiang

Theses and Dissertations

Cannabis (Marijuana) has multiple effects on the human body, such as analgesia, euphoria and memory impairment. Delta-9 tetrahydrocannabinol (D9-THC), the active ingredient in cannabis, binds to cannabinoid receptors, seven-transmembrane G protein-coupled receptors (GPCRs) that mediate a variety of physiological functions. GPCRs were believed to function only in homomeric forms, however, recent findings show that different GPCRs can also form heteromeric complexes that may expand their signaling properties. In this study, we focused on Cannabinoid CB1 receptor (CB1R) heteromers with the mu-opioid receptor (MOR) and the Dopamine type 2 receptor (D2R), respectively. We utilized a variety of techniques, such as the …

Effects Of Hiv-1 Tat And Drugs Of Abuse On Antiretroviral Penetration Inside Different Cns Cell Types, Sulay H. Patel

Theses and Dissertations

Human immunodeficiency (HIV) infection can result in neurocognitive deficits in about one-half of infected individuals. Despite excellent systemic effectiveness, restricted antiretroviral penetration across the blood-brain barrier (BBB) is a major limitation in fighting HIV infection within the central nervous system (CNS). Drug abuse exacerbates cognitive impairment and pathologic CNS changes in HIV-infected individuals. This work investigates the effects of the HIV-1 protein, Tat, and drugs of abuse on factors affecting drug penetration into the brain.

Firstly, an in vitro model of the blood-brain barrier was built to study effects of HIV-1 Tat and methamphetamine (Meth) on integrity and function of …

Relationship Between Patient-Health Coach Interactions And Changes In Markers Of Glucose Homeostasis, Jason P. Nagy

Theses and Dissertations

Diabetes and insulin resistance are on the rise in the United States. Early detection and deployment of therapies has allowed for the reversal of pancreatic beta cell damage. Unfortunately, not all providers can offer the support to facilitating the required life style modifications. The introduction of clinical health consultants (CHC) as supplemental care has improved patient health for a variety of chronic diseases. Missing in the literature are studies investigating the correlation between the number of CHC interactions and improvement in biomarkers.

The study utilized a non-experimental, retrospective study design to evaluate the relationship between the use between the use …

Critical Consciousness, Racial Identity, And Appropriated Racial Oppression In Black Emerging Adults, Keyona Allen

Theses and Dissertations

The present study explored private regard and public regard, two subcomponents of racial identity, as mediators of the association between critical consciousness and appropriated racial oppression. In a sample of 75 Black emerging adults, ages 18-25, the current study examined (1) the relationships between critical consciousness, racial identity, and appropriated racial oppression and (2) whether racial identity mediates the relationship between critical consciousness and appropriated racial oppression. Relationships in the expected direction were evident between private regard and both critical consciousness and appropriated racial oppression. Relationships in the expected direction were evident between public regard and critical consciousness. Further, mediation …

Family Planning And Hiv Interventions Among Women In Low-Income Settings, Steven P. Masiano

Theses and Dissertations

This dissertation examines the effectiveness of interventions related to family planning and the uptake of HIV-related preventive services among women in low-income settings. Women in low-income settings and living with HIV face many barriers to care, including limited access to services for family planning and HIV-related preventive care. At the same time, national, regional, and global efforts are looking for interventions to help control rapid population growth, create an HIV-free generation, and provide adequate preventive care for those living with HIV. This dissertation cuts across these issues and can help to inform debate and policies to address these issues.

This …

Drug Delivery With Light, Patrick S. Dupart

Theses and Dissertations

Cancer is responsible for about 25% of deaths in developed countries and for 15% of all deaths worldwide. Cancer is a devastating disease and while there have been great advances in the development of anticancer drugs, off-target toxicity is a major limitation with conventional cancer chemotherapy. The consequence of this form of treatment results in the killing of healthy and rapidly-growing non-cancerous cells including cells in the bone marrow; hair follicles; and cells in the mouth, digestive tract, and reproductive system. In addition to these general effects, certain anticancer drugs can have other associated toxicities. For instance, the anticancer drug …

Relationships Among Parenting Stress, Parenting Practices, And Conduct Problems In African American Mothers Of Children With And Without Adhd, Amanda Parks

Theses and Dissertations

Parents of children with attention-deficit/hyperactivity disorder (ADHD) endorse increased levels of parenting stress and subsequently employ ineffective parenting practices. For children with comorbid conduct problems, mothers report more parenting stress than mothers of children with ADHD alone. I investigated the relationships among child ADHD diagnostic status, parenting stress, parenting behaviors (i.e., involvement and positive parenting) and child conduct problems in 78 African American mothers of children with and without ADHD. Mothers completed a demographic questionnaire, a semi-structured clinical interview, the ADHD Rating scale (also completed by teachers), the Impairment Rating Scale, the Parenting Stress Index – Short Form, and the …

"To Conceive With Child Is The Earnest Desire If Not Of All, Yet Of Most Women": The Advancement Of Prenatal Care And Childbirth In Early Modern England: 1500-1770, Victoria E.C. Glover

Theses and Dissertations

This thesis analyzes medical manuals published in England between 1500 and 1770 to trace developing medical understandings and prescriptive approaches to conception, pregnancy, and childbirth. While there have been plenty of books written regarding social and religious changes in the reproductive process during the early modern era, there is a dearth of scholarly work focusing on the medical changes which took place in obstetrics over this period. Early modern England was a time of great change in the field of obstetrics as physicians incorporated newly-discovered knowledge about the male and female body, new fields and tools, and new or revived …

Reducing Sepsis Mortality: A Cloud-Based Alert Approach, Janet A. Zink

Theses and Dissertations

The aim of this study is to examine the impact of a cloud-based CDS alerting system for SIRS, a precursor to sepsis, and sepsis itself, on adult patient and process outcomes at VCU Health System. The two main hypotheses are: 1) the implementation of cloud-based SIRS and sepsis alerts will lead to lower sepsis-related mortality and lower average length of stay, and 2) the implementation of cloud-based SIRS and sepsis alerts will lead to more frequent ordering of the Sepsis PowerPlan and more recording of sepsis diagnoses. To measure these outcomes, a pre-post study was conducted. A pre-implementation group diagnosed …

Decoding The Signaling Of The D2r-2ar Heteromer: Relevance To Schizophrenia, Miao Huang

Theses and Dissertations

Schizophrenia is a severe mental disorder affecting ~1% of world population. Two G protein coupled receptors (GPCRs): Gi-coupled dopamine D2 receptor (D₂R), and Gq-coupled serotonin 2A receptor (2AR), are targeted by the typical and atypical antipsychotic drugs to treat schizophrenia. These two receptors have been shown to co-localize in brain regions relevant to schizophrenia, including the ventral tegmental area (VTA), striatum, and prefrontal cortex (PFC). Studies in our lab characterized the integrated signaling of the D₂R-2AR heteromer and found that both the Gi activity of D₂R and the Gq activity of 2AR were potentiated …

The Impact Of Mother–Father Relationship, Social Support And Neighborhood Context On Preterm Birth, Timothy O. Ihongbe

Theses and Dissertations

Background: Preterm birth is a major public health concern in the US. Previous studies have suggested that quality of the mother-father relationship, social support, and neighborhood violence may be associated with preterm birth; however, findings are equivocal.

Objectives: The main objectives of this dissertation were: 1) to determine the modifying effect of perceived residential environment on the association between quality of mother–father relationship and preterm birth in a sample of African-American women, 2) to examine whether the receipt of social support modifies the association between neighborhood violence exposure and preterm birth in a nationally representative sample of US women, and …

Effects Of A 2-Week Exercise Intervention On Heart Rate Variability In Individuals With Low And High Anxiety Sensitivity, Hannah M. Kotarski

Theses and Dissertations

Anxiety Sensitivity (AS), the belief that anxiety-related sensations may have harmful implications, can alter autonomic nervous system (ANS) function. Exercise has previously been shown to reduce AS; however, the effects of an exercise intervention on heart rate variability (HRV), a measure of ANS function, has not been evaluated in individuals with high AS. This study sought to 1) compare resting HRV in individuals with either low (LAS) or high AS (HAS) and 2) evaluate the effects of a 2-week exercise intervention on HRV and AS. Using the Anxiety Sensitivity Index (ASI-3), participants were identified as LAS (n=9; ASI-3=5.89±1.39) or HAS …

Nicotinic Acetylcholine Receptor Dependent Effects Of Nicotine On Hek293t And Hbo Cells, James D. Larsen

Theses and Dissertations

T2R receptors are the classical bitter taste receptors which detect and transduce bitter taste in a subset of taste receptor cells (TRCs). The TRPM5-dependent T2Rs are G-protein coupled receptors (GPCRs) and are linked to G protein, gustducin to initiate an intracellular signaling cascade for the transduction of bitter tastants. Nicotine is bitter. However, at present the transduction mechanisms for the detection of nicotine in are poorly understood. Previous studies from our laboratory using TRPM5 knockout (KO) mice demonstrated that the T2R pathway is insufficient in explaining the taste perception of nicotine. TRPM5 KO mice elicited chorda tympani (CT) taste nerve …

Neutronics Studies On The Nist Reactor Using The Ga Leu Fuel, Kyle A. Britton

Theses and Dissertations

The National Bureau of Standards Reactor (NBSR) located on the National Institute of Standards and Technology (NIST) Gaithersburg campus, is currently underway of fuel conversion from high enriched uranium (HEU) fuel to low enriched uranium (LEU) fuel. One particular challenging part of the conversion of the NBSR is the high average flux level (2.5×10¹⁴ n/cm²-s) required to maintain experimental testing capabilities of the reactor, without significant changes to the external structures of the reactor. Recently the General Atomics (GA) Training Research Isotopes General Atomics (TRIGA) fuel has shown some promising features as a LEU candidate for the …

Toxicological Inhalation Effects Of Metal-Based Nanoparticle Aerosols As Studied By A Portable In Vitro Exposure Cassette, Lynn E. Secondo

Theses and Dissertations

The toxicology of aerosols in occupational settings is often performed through particle collection on a filter followed by reconstitution into cell culture media which can alter the biological effects. Current in vitro exposure systems require additional instruments to control temperature and humidity, making the system bulky and difficult to take to the field. The Portable In Vitro Exposure Cassette (PIVEC) was designed for personal monitoring, characterized using copper nanoparticles, tested with alveolar cells, and set-up for real-time monitoring. Three differently sized copper nanoparticles, 40-800 nm, were dispersed as a dry aerosol and measured gravimetrically and on a number concentration basis …

The Effect Of Biologic Materials And Oral Steroids On Radiographic And Clinical Outcomes Of Horizontal Alveolar Ridge Augmentation., Amy Reichert

Theses and Dissertations

The purpose of this study was to investigate if the addition of biologic materials and/or oral steroids would affect horizontal bone gain, or the bone density of the grafted bone in horizontal alveolar ridge augmentations. A retrospective chart review was completed to assess the clinical and radiographic outcomes of 53 ridge augmentation patients. An average bone gain of 3.6mm of width was found in our study based on radiographic analysis. There were no statistically significant differences found in the linear bone gain with the addition of biologic materials and steroids. A marginally statistically significant difference was found in the bone …

Bed And Breakfast: The Role Of Sleep And Affect In Breakfast Intake, Ashley R. Macpherson

Theses and Dissertations

Breakfast intake is associated with numerous positive physical and mental health outcomes, yet breakfast skipping remains common in adults. Chronotype and sleep show potential as predictors of breakfast intake; however the existing literature has methodological limitations and fails to examine how psychological mechanisms might explain the relation between sleep and breakfast. The current investigation explored the association of means and variability of sleep behaviors (bedtime, midsleep, sleep duration) as predictors of breakfast intake frequency and high-protein breakfast intake frequency. Additionally, the role of positive and negative affect as mediators in the sleep—breakfast association was examined. Hierarchical regressions and PROCESS parallel …

A Stakeholder Examination Of Gestational Weight Gain Guidelines, Melissa Kwitowski

Theses and Dissertations

Obesity is a significant health concern for women of childbearing age. More than 40% of women have a Body Mass Index (BMI) in the overweight or obese ranges at the time they conceive, posing significant health risks for both mother and child. Excessive weight gain during pregnancy is common and associated with numerous deleterious complications. The Institute of Medicine published gestational weight gain (GWG) guidelines based on prepregnancy BMI. However, more than 50% of women gain in excess of these recommendations. Further, many women report receiving minimal guidance from their healthcare providers regarding weight gain, nutrition, and physical activity during …

Estimating The Respiratory Lung Motion Model Using Tensor Decomposition On Displacement Vector Field, Kingston Kang

Theses and Dissertations

Modern big data often emerge as tensors. Standard statistical methods are inadequate to deal with datasets of large volume, high dimensionality, and complex structure. Therefore, it is important to develop algorithms such as low-rank tensor decomposition for data compression, dimensionality reduction, and approximation.

With the advancement in technology, high-dimensional images are becoming ubiquitous in the medical field. In lung radiation therapy, the respiratory motion of the lung introduces variabilities during treatment as the tumor inside the lung is moving, which brings challenges to the precise delivery of radiation to the tumor. Several approaches to quantifying this uncertainty propose using a …

Orientia Tsutsugamushi Modulates Endoplasmic Reticulum Stress To Benefit Its Intracellular Growth And Targets Nlrc5 To Inhibit Major Histocompatibility Complex I Expression, Kyle G. Rodino

Theses and Dissertations

Scrub typhus, caused by the obligate intracellular bacterium Orientia tsutsugamushi, afflicts one million people annually. Despite being a global health threat, little is known about O. tsutsugamushi pathogenesis. Here, we demonstrate that O. tsutsugamushi modulates the ER and ER-associated processes as mechanisms of nutritional virulence and immune evasion. To obtain amino acids to fuel replication, O. tsutsugamushi simultaneously induces ER stress and the unfolded protein response (UPR) while inhibiting ER-associated degradation (ERAD) during early infection time points. During exponential growth, the bacterium releases the ER bottleneck, resulting in generation of ERAD-derived amino acids that it parasitized for replication. …

Targeting Monoacylglycerol Lipase For The Reversal And Prevention Of Paclitaxel-Induced Allodynia In Mice, Zachary Curry

Theses and Dissertations

Chemotherapy-induced peripheral neuropathy (CIPN) is a side-effect of chemotherapy causing pain in the hands and feet. In particular, paclitaxel causes CIPN lasting for years without effective treatment. There is a strong need for analgesics to both treat and prevent CIPN. One system containing multiple targets to treat CIPN is the endogenous cannabinoid system. This system consists of cannabinoid type 1 (CB₁) and type 2 (CB₂) receptors primarily expressed on presynaptic neurons and cells of the immune system, respectively. Inhibition of monoacylglycerol lipase (MAGL), which hydrolyzes the endogenous cannabinoid 2- arachidonoylglycerol (2-AG), with JZL184 or MJN110 produces …

Glycosaminoglycan Lyases In The Preparation Of Oligosaccharides, Alhumaidi B. Alabbas

Theses and Dissertations

Glycosaminoglycans are heterogeneous polysaccharides that mediate important biological functions. There has been considerable interest in deciphering the precise GAG sequences that are responsible for protein interactions. In fact, several GAG oligosaccharides have been discovered to date as targeting proteins with higher level of specificity. Yet, it has been difficult to develop GAG oligosaccharides as drugs. One of the key reasons for this state of art is that GAG synthesis is extremely challenging and is highly structure-specific. Thus, much of the biology and pharmacology of GAG remains unknown and unexploited to date.

An alternative approach is to prepare GAG oligosaccharides using …

Mental Health Difficulties And Service Use Of Incarcerated Women: The Influence Of Violence Perpetration And Victimization, Rachel C. Casey

Theses and Dissertations

The present study aimed to expand the knowledge base regarding incarcerated women’s experiences with violence and their mental health with the goal of identifying avenues for more tailored, compassionate responses to their mental health difficulties in both macro and direct practice contexts. To achieve this aim, a secondary data analysis was performed using data from the Survey of Inmates in State Correctional Facilities (SISCF) completed by the Bureau of Justice Statistics (BJS) in 2004. Six research questions pertaining to women’s experiences with violence and their mental health difficulties and service utilization guided the inquiry, which involved univariate, bivariate, and multivariate …

Counterregulatory Effects Of Ptx3 On Inflammation And Cellular Aging, Aaron L. Slusher

Theses and Dissertations

Pentraxin 3 (PTX3) is a vital regulator of innate immune function that has been shown to counterregulate pro-inflammatory signaling and protect against the development of cardiovascular disease (CVD). Less is known about how PTX3 may mitigate against CVD risk by regulating the pro-inflammatory response at the cellular level. Therefore, this dissertation details four manuscripts which aimed to examine the capacity of PTX3 to regulate the innate immune response of peripheral blood mononuclear cells (PBMCs) isolated from healthy adults. Manuscript 1 examined the capacity of PTX3 to alter the inflammatory milieu following in vitro stimulation of isolated PBMCs with the pro-inflammatory …