Master of Science (MS), University of Toledo, 2018, Biomedical Sciences (Medical Microbiology and Immunology)

Every year there are an increasingly large number of new cases of end-stage-renal-disease (ESRD) in the United States, with 124,111 patients progressing to ESRD in 2015 alone. Of these cases, 30% are attributable to hypertension. Kidney transplantation is the best treatment for ESRD, however, its use is limited by the recipient's immune response against the transplant. The use of advanced immunosuppression has allowed for significant improvement in short to medium term transplant survival, however, the long-term transplant survival remains poor due to chronic rejection. The median transplant survival is only 10.9 years from deceased donors and 14.8 years from living donors. Chronic rejection is characterized by the gradual development of fibrosis and nephropathy which can be identified as early as 3 months post-transplant and in 50% of biopsies 1 year post-transplant. A common comorbidity to graft rejection is hypertension, as 70-83% of recipients are hypertensive or become hypertensive post-transplant. Interestingly, hypertension also leads to the development of fibrosis and nephropathy. We sought to develop a model of chronic renal allograft rejection in the rat, in which the interplay hypertension and chronic allograft rejection could be studied. We hypothesized that with the correct tacrolimus regimen, a model of chronic renal allograft rejection can be developed in the rat that includes a hypertensive salt-sensitive Dahl-S donor.

Committee: Stanislaw Stepkowski PhD,DVM,DSc (Committee Chair); Steven Haller PhD (Committee Member); Kevin Pan PhD,MD (Committee Member) Subjects: Immunology; Medicine

Doctor of Philosophy (PhD), University of Toledo, 2020, Biomedical Sciences (Molecular Medicine)

Hypertension or elevated blood pressure (BP) is described as systolic BP over 140 mmHg. It is a significant risk factor for stroke, cardiac and renal disorders. BP is a complex polygenic trait. The genome, microbiome, and environment together regulate BP. Dietary salt (sodium chloride) consumption is one of the most significant known environmental factors that is associated with BP regulation. Eating too much sodium leads to salt-sensitive hypertension. In my dissertation, I present multiple studies, each focused on the contributions of the genome, microbiome, circadian rhythm and metabolism, respectively, to the regulation of salt-sensitive hypertension. Through substitution mapping in animal models and Genome Wide Association Studies (GWAS) in humans, we already know that the genome plays a key role in blood pressure regulation. However, the precise details on the constituent nucleotides on our DNA that regulate BP are still sparse. Positional cloning strategies are applied to identify such nucleotides. In my study on one such positional cloning project, I focused on a rat genetic locus previously mapped to a <1kb region and prioritized a coding-base pair as a candidate quantitative trait nucleotide (QTN) for BP. To test the effect of substituting this single nucleotide on BP, we modified the genome of the genetically hypertensive Dahl S rat using the CRISPR/Cas9 Knock-In approach to generate a rat model which had a single G to T substitution at this prioritized candidate locus coding for Secreted Phosphoprotein 2 (Spp2). The resultant genome-edited model with the G/T substitution demonstrated a sex-specific lowering of BP exclusively in male rats. Further, this locus also demonstrated sex-specific pleiotropy, because the genome-edited model showed a lower bone mass in female rats, but had no effect on male rats. Overall, my study is the first to (1) provide proof-of-principle for advanced positional cloning of a single QTN, (2) identify Spp2 as a Quantit (open full item for complete abstract)

Committee: Bina Joe (Committee Chair); Matam Vijay-Kumar (Committee Member); Robert Blumenthal (Committee Member); Ivana De La Serna (Committee Member); Beata Lecka-Czernik (Committee Member) Subjects: Biomedical Research; Health Sciences; Medicine; Microbiology; Molecular Biology; Physiology

Doctor of Philosophy, Case Western Reserve University, 2019, Molecular Medicine

The beta-adrenergic receptor (bAR) exists in an equilibrium of inactive and active conformational states, which is modulated by ligands resulting in downstream signaling. In addition to cAMP, bAR regulates hypoxia-inducible factor 1 (HIF-1). We hypothesized that HIF-1 signaling occurs via a unique, independent bAR conformation and that Pulmonary Arterial Hypertension (PAH) patients with HIF-biased conformations would have blunted cAMP response. We found isoproterenol and salbutamol, both cAMP agonists, had opposing effects on HIF-1 in cells and mice. Additionally, hypoxia blunted agonist-stimulated cAMP in vitro, consistent with receptor equilibrium shifting towards HIF-activating conformations. bAR overexpression in cells increased HIF-1 activity and glycolysis which was blunted by HIF-1 inhibitors, suggesting increased bAR increases basal HIF-1 signaling. Because PAH is also characterized by HIF-related glycolytic shift, we dichotomized PAH patients in the PAHTCH trial (NCT01586156) based on right ventricular glucose uptake to evaluate bAR signaling. Patients with high glucose uptake had more severe disease than those with low uptake and had no response to bAR ligands. The findings expand the paradigm of bAR regulation and uncover a novel PAH subtype that might benefit from b-blockers. Circulating cell-free mitochondrial components are well characterized as mediators of inflammation. Recent studies show cells also release microparticles (MPs) containing intact mitochondria under conditions of stress or injury. However, detection of cell-free mitochondria and their cellular origin has not been studied in non-pathological conditions. Thus, we hypothesize that intact mitochondria are detectable in the circulation under physiological conditions. To test this, plasma MPs were analyzed via flow cytometry. Murine platelet-depleted plasma showed a small cluster of MPs which was 65% positive for the mitochondrial marker MitoTracker Green (MT Green). Additionally, transg (open full item for complete abstract)

Committee: Serpil Erzurum MD (Advisor); Sathyamangla Prasad PhD (Committee Chair); Kristin Highland MD (Committee Member); Bela Anand-Apte MBBS, PhD (Committee Member); Satish Kalhan MD (Committee Member) Subjects: Biology; Biomedical Research; Molecular Biology; Physiology

Master of Science (MS), Ohio University, 2009, Psychology (Arts and Sciences)

Hypoalgesia is common in persons with and at risk for hypertension (Ghione, 1996; France, 1999) and may result from dampened affective responses to painful stimuli (Wilkinson & France, 2009; Jorgensen et al., 1996). Generally, pleasant affective stimuli decrease pain, whereas unpleasant affective stimuli increase pain (Rhudy et al., 2005). In the current study, it was hypothesized that the buffering effect of positive affect and the exacerbating effect of negative affect on pain would be less for those at increased risk for developing hypertension. Participants (N=117) were stimulated at 120% of their nociceptive flexion reflex (NFR) threshold while viewing pleasant, unpleasant, and neutral images. Electromyographic response magnitudes, pain ratings, valence ratings, and arousal ratings were obtained. The hypothesis was not supported, possibly because the valence and arousal ratings showed little variability as a function of hypertension risk. It appears that dampened affect is not the mechanism of hypoalgesia in those at risk for hypertension.

Committee: Christopher R. France (Advisor); Jeff Vancouver (Committee Member); Kathi Heffner (Committee Member) Subjects: Psychology

Master of Science in Biomedical Sciences (MSBS), University of Toledo, 2007, College of Graduate Studies

The etiology of essential hypertension (EH) is greatly impacted by individual genetic constitution. This provides the rationale to identify genes that have a role in BP regulation. Human studies are confounded by genetic heterogeneity making it difficult to conclusively identify the underlying genetic causes of EH. Alternatively, by using homozygous inbred rat strains, genetic variability and environmental influences are minimized. The Dahl salt-sensitive (S) and Lewis (LEW) inbred rat strains differ in their susceptibility to hypertension. To identify the genomic region accounting for the contrasting BP phenotype, congenic strains (S.LEW) was generated and tested for BP. S.LEW refers to the incorporation of a segment of the LEW rat genome (normotensive donor strain) into the S rat (hypertensive recipient strain) genetic background. The presence of LEW alleles lowered BP significantly in two S.LEW congenic rat strains compared to the S. These results implicate a locus on rat chromosome 1, spanning 793 kilobases (Kb), in BP regulation. This research has focused on identifying and characterizing the genetic differences between S and LEW within this region. This has been accomplished by 1) Fine resolution substitution mapping: Screening a large F2 population (n=2652) for meiotic recombination, within the 793 Kb interval, resulted in three congenic substrains: S.LEW(D1MCO4X1X3BX1X1), S.LEW(D1MCO4X1X3BX1X2 ) and S.LEW(D1MCO4X1X3BX2X1). BP measurements of these strains are anticipated to provide in vivo evidence for the further localization of crucial BP regulating segments. 2) Characterizing coding sequence variations: Coding sequence analysis of the two predicted genes within the 793 Kb region revealed two naturally occurring amino acid changes in LOC306664 (Adamts16) between S and LEW and 3) Utilizing in silico analysis to detection segments within the 793 Kb region that contain regulatory elements and noncoding conserved sequences which do not encode for protein. The (open full item for complete abstract)

Committee: Bin Joe (Advisor) Subjects:

Master of Science, The Ohio State University, 1967, Graduate School

Committee: Not Provided (Other) Subjects:

Doctor of Philosophy, The Ohio State University, 2024, Biomedical Engineering

Right ventricular (RV) function strongly associates with mortality in patients with pulmonary hypertension (PH). Survival is associated with right ventricular function rather than pulmonary vascular resistance or PA pressure. Optimization of RV assessment is an identified priority in PH clinical research, alongside phenotyping and identifying markers of increased risk. Echocardiography and cardiac magnetic resonance (CMR) imaging are both used to quantify RV function but CMR can be used to reliably obtain quantitative information about RV shape, size, and remodeling. A current unmet clinical need is the identification of clinically meaningful imaging features that clearly distinguishes between normal and abnormal RV structure and function. Right ventricle global longitudinal strain has been shown to associate with outcomes in PH and is typically measured via echocardiography. Measures of strain help to provide insight into the biomechanics of the RV (diastolic stiffness) and function. Changes in ventricular dynamics during ejection and filling may associate with the biomechanics of the RV. We hypothesized RV strain will be different in advanced RV dysfunction and the aim of the study was to evaluate RV strain and instantaneous strain rates throughout the cardiac cycle from CMR images in patients with pulmonary hypertension. We utilized machine learning methods to evaluate advanced hemodynamic variables obtained from right heart catheterization and cardiac magnetic resonance imaging. Unsupervised machine learning algorithms allow us to reduce high-dimensional data into handleable chunks while preserving the intersection of each dimension and its impact. By assessing RV remodeling and function through hemodynamic, clinical, and imaging data, we were able to identify multiple unique functional phenotypes that reflect states of RV dysfunction. Working with advanced hemodynamics, we identified five subphenotypes of RV dysfunction. We found a subtype of particip (open full item for complete abstract)

Committee: Rebecca Vanderpool (Advisor); Seth Weinberg (Committee Member); Scott Visovatti (Committee Member); Rizwan Ahmad (Committee Member) Subjects: Biomedical Engineering

DNP, Walsh University, 2024, Nursing

Hypertension (HTN) is one of the most diagnosed conditions and is increasing in prevalence at an extreme rate. Although evidence-based recommendations include self-measured blood pressure (SMBP) twice daily, many older adults do not monitor their blood pressure outside of the clinic setting. Consistent education from healthcare professionals to patients on how to correctly measure blood pressure and address other risk factors of hypertension is lacking. This research study was designed to implement and evaluate the effectiveness of an SMBP training program for registered nurses (RNs) providing case management support to community-based older adults with essential hypertension in a Managed Care Organization (MCO) across Wisconsin. RN case managers completed a learning module and their hypertension management knowledge was measured at three points, pre-intervention, immediately post-intervention, and one-month post-intervention. Results were then compared via RM-ANOVA. A retrospective review of patient charts was also completed to determine if there was an increase in the patient recorded frequency of SMBP following the RN case manager training and compared via independent t-tests. The RN case managers' hypertension management knowledge increased significantly following education, with a slight decrease in scores over time. Retrospective chart reviews revealed that the frequency of documented patient blood pressure self-measurements increased significantly following RN case manager education. Implementing an evidence-based SMBP training program for RN case managers is a successful intervention to support the management of essential hypertension in community-based older adults.

Committee: Shelly Amato-Curran (Advisor); Cheryl Bradas (Advisor) Subjects: Health Care Management; Health Education; Nursing

PHD, Kent State University, 2024, College of Public Health

Background: Hypertension or sustained high blood pressure (BP) is one of the strongest risk factors for most health complications and a major contributor to premature death. Despite awareness and existing knowledge to prevent and control the condition, it remains a major public health challenge and a significant burden on health systems. The multifaceted complexity of the condition, lack of standardized recommendations for all clinical settings, and conflicting evidence of patient outcomes necessitated further research. Methods: This dissertation is comprised of three retrospective cohort studies that explored outcomes of patients with a hypertension diagnosis within a major healthcare system in the United States. First, using a quasi-experimental approach, we assessed whether an outpatient quality improvement program was equally effective at improving BP control among Black and White patients before (N=71,964) and after (N=94,176) program implementation. Next, we investigated the impact of a secondary diagnosis of hypertension (i.e., another condition was established as the cause of hospital admission) on all-cause inpatient mortality among a propensity-weighted cohort (N=90,388). Finally, among a sample of patients with a hypertension diagnosis (N=44,076), we evaluated whether BP control status at admission predicted the location to which the patient was immediately discharged at the end of their hospital stay. Results: We found that the gap in BP control attainment between White and Black patients widened after the outpatient program was introduced (7.4% in 2015 vs. 10.0% in 2016, p<.0001) and treatment differences during program implementation may have contributed to the increased racial disparity. Within the hospital setting, those with a hypertension diagnosis had a lower incidence of inpatient mortality compared to those without a hypertension diagnosis (1.0% vs. 1.6%, p<.0001). Several primary diagnoses and clinical factors were identified as factor (open full item for complete abstract)

Committee: Lynette Phillips (Committee Chair); Elizabeth Pfoh (Committee Member); Maggie Stedman-Smith (Committee Member); Melissa Zullo (Committee Member) Subjects: Epidemiology; Public Health

Doctor of Philosophy, The Ohio State University, 2024, Biomedical Sciences

Heart failure (HF) is a complex heterogeneous syndrome characterized by altered left ventricular ejection function and impacts over six million individuals in the United States. Among cancer survivors, cardiovascular mortality due to HF is prevalent.1,2 Despite improvements in the medical and surgical management of HF, mortality rates remain high, with only modest improvements in survival during the past decade. Proper systolic heart function requires coordinated activation and force transmission throughout the myocardium. Cardiomyocytes have developed intricate molecular mechanisms to control both electrical and mechanical functions in response to physiological and pathological stressors. Therefore, active targets for diagnostic and therapeutic approaches for HF are currently centered on pathways that influence both the electrical and structural function of cardiomyocytes. The work described herein explores the mechanisms underlying electrical and structural dysfunction in tyrosine kinase inhibitor (TKI) cardiotoxicity and βII-spectrin (Sptbn1) deficient HF. Genetic or acquired (i.e., drug-induced cardiotoxicity) changes in signaling pathways responsible for electrical and structural homeostasis can lead to the development of lethal arrhythmias and HF. Several chemotherapeutic agents, including TKIs, are associated with arrhythmia and HF in patients with or without preexisting cardiovascular disease. It has been postulated that TKIs may induce HF by causing direct myocardial damage, culminating in reduced cardiac inotropy, lusitropy, and chronotropy. However, the mechanisms by which these phenomena develop or contribute to ventricular arrhythmias and cardiac dysfunction are incomplete. We first describe that pazopanib, a second-generation TKI, alters cardiomyocyte excitability in patients using a retrospective chart review and recapitulated these findings in two mouse models using surface electrograms. Cellular and computational model studies revealed th (open full item for complete abstract)

Committee: Sakima Smith (Advisor); Brandon Biesiadecki (Committee Member); Mark Ziolo (Committee Member); Jill Rafael-Fortney (Committee Member); Thomas Hund (Committee Member) Subjects: Cellular Biology; Molecular Biology; Physiology

MS, University of Cincinnati, 2024, Medicine: Clinical and Translational Research

Background: Pulmonary hypertension (PH) frequently complicates the course of patients with left heart disease (PH-LHD), and it is associated with worse clinical outcomes. Mortality calculators for PH-LHD are lacking, and it is unclear whether any risk prediction tools originally derived from other forms of PH can accurately predict outcomes in patients with PH-LHD. Methods: We retrospectively analyzed data from 161 patients with a diagnosis of PH-LHD referred to our pulmonary hypertension center from 2016 to 2022. We calculated the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL 2.0) risk score and categorized patients as low, intermediate, or high-risk. We assessed survival and risk discrimination at 1—and 3-yrs using Kaplan-Meier, Cox proportional hazards, and concordance index. Results: At the first outpatient visit, 15% of patients were stratified as low-risk, 27% as intermediate, and 57% as high-risk. Cumulative 1-year survival rates were 100%, 94%, and 91% for low, intermediate, and high-risk strata, respectively. Cumulative 3-year survival rates were 96%, 89%, and 70% for low, intermediate, and high-risk strata, respectively. We found no difference in outcomes at 1 yr between risk groups. High-risk patients had a significantly higher risk of death at 3 years using REVEAL 2.0 (HR 5.32, p<0.001). However, REVEAL 2.0 accurately discriminated high-risk patients; the Cox proportional hazard ratio was not statistically different between patients classified as intermediate-risk compared to low-risk. Conclusion: REVEAL 2.0 accurately predicted 3-year survival in PH-LHD patients with high-risk features. However, the survival rates in patients classified as intermediate-risk were not significant, suggesting inaccurate classification for this group of patients.

Committee: Patrick Ryan Ph.D. (Committee Chair); Roman Jandarov Ph.D. (Committee Member); Jean Elwing (Committee Member); Jennifer Cook M.D. (Committee Member); Jose Gomez Arroyo M.D. Ph (Committee Member) Subjects: Surgery

Doctor of Philosophy, Case Western Reserve University, 2024, Physiology and Biophysics

Functional elastin fibers within extracellular matrix of the arterial wall facilitate passive distensibility and recoil, which is critical to maintaining blood flow. Elastin fragmentation decreases functional elastin level and is associated with aging, contributing to age-related arterial stiffening, an independent risk factor for the development of hypertension. The effects of elastin deficiency in large elastic vessels are well-known, but the impact on resistance vessels, crucial for renal perfusion and blood pressure regulation, is less explored. Furthermore, elastin insufficiency in mice is associated with elevated blood pressure, which is more pronounced in male mice than female mice when compared to their respective wild-type counterparts. However, the mechanisms underlying the sex-related differences in elastin-insufficient mice have not been explored. Using an animal model of elastin haploinsufficiency (Eln+/-), we demonstrated that loss of elastin exacerbates structural and biomechanical properties of intra-renal arteries in young Eln+/- female mice. These changes manifest as increased vascular stiffness and increased fragmentation, leading to blunted responses to increased renal perfusion pressure and impaired renal autoregulation. We further explored whether renal dysfunction contributes to hypertension in these mice and whether this relationship is modulated by ovarian hormones. Our findings establish that ovarian hormones mitigate the hypertensive phenotype in female Eln+/- mice. Though these mice exhibit impaired pressure natriuresis response, the hypertensive phenotype is not sodium-dependent. Instead, the sustained elevation in blood pressure is in part driven by increased activity of the renin-angiotensin system (RAS). Additionally, diuresis and urine concentrating ability were found to be impaired in female Eln+/- mice despite increased aquaporin 2 channel expression. Furthermore, the reduced sensitivity to vasopressin (V2) receptor blockade in Eln (open full item for complete abstract)

Committee: Patrick Osei-Owusu (Advisor); George Dubyak (Committee Chair); Jessica Wagenseil (Committee Member); Julian Stelzer (Committee Member); Jeffery Garvin (Committee Member) Subjects: Physiology

Doctor of Philosophy, University of Toledo, 2023, Experimental Therapeutics

Alzheimer's disease (AD) is the most common cause of dementia and is a progressive neurodegenerative disease, impacting a substantial proportion of the aging population worldwide. It is a complex disease with many varied symptoms, including vascular manifestations. The association between vascular manifestations, such as long-term hypertension, and cognitive decline in AD has been established, but is not well understood. Primary cilia, a sensory organelle, are found on the surface of most mammalian cells and play a key role in sensing the external environment. When the structure or function of cilia is disrupted, it can lead to disorders known as ciliopathies, which have a wide range of symptoms. Many ciliopathies can lead to multisystem organ deficits, such as the central nervous system, vasculature, or renal system. There are a multitude of receptors, such as the muscarinic acetylcholine receptors in the cholinergic system, which have previously been shown to regulate cognition and the cardiovascular system. We hypothesize that targeting the muscarinic acetylcholine receptor 3 (AChM3R) on the primary cilia may possess cognitive and vascular protective effect, due to nitric oxide regulation, and ultimately improve therapeutic efforts for AD patients. In this work, we discovered that AChM3R and Phosphatidylinositol 4,5-bisphosphate (PIP2), a downstream effector molecule of AChM3R activation, are localized to the primary cilia of cerebrovascular endothelial cells. Amyloid beta (Aβ) peptide treatment disrupted primary cilia structure, significantly shortening cilia length and frequency of ciliation, and this effect was rescued with AChM3R activation. These findings suggest that primary cilia may be a signaling hub for AChM3R modulation and AChM3R activation can rescue the disruption effect on primary cilia structure from Aβ treatment. We generated and validated a vascular specific AChM3R knockout mouse model (VECre_AChM3Rf/f), which was associated with high blood pr (open full item for complete abstract)

Committee: Wissam AbouAlaiwi (Committee Chair); James Burkett (Committee Member); Isaac Schiefer (Committee Member); William Messer Jr. (Committee Member) Subjects: Behavioral Sciences; Biomedical Research; Neurosciences; Pharmacology

Doctor of Philosophy, Case Western Reserve University, 2024, Nursing

The study investigates the multifaceted landscape of medication adherence and its intricate ties to health outcomes among older adults living with hypertension in the United States. Employing the Self-Regulation Model (SRM) as a guiding framework, this research delves into the interplay between psychological, demographic, and health-related factors, shedding light on their collective influence on adherence behavior and its consequential impact on blood pressure control, stroke risk, and activities of daily living (ADL). The research reveals significant correlations between psychological perceptions and medication adherence, aligning with the SRM's emphasis on beliefs and attitudes as key determinants of health-related behaviors. Older adults exhibiting positive perceptions of hypertension demonstrated heightened medication adherence, suggesting that viewing hypertension positively fosters a greater commitment to medication regimens as a fundamental self-management strategy. Furthermore, the study uncovers a substantial link between depression and medication non-adherence, underscoring the significance of addressing mental health concerns to improve adherence rates. The impact of medication adherence on health outcomes becomes evident in its correlation with blood pressure control and ADL performance. Adherence to antihypertensive medication emerges as a key determinant of systolic blood pressure levels, emphasizing the pivotal role of consistent adherence in optimizing cardiovascular health. Additionally, medication adherence is linked to enhanced ADL performance, showcasing its broader influence on functional independence and overall well-being. Notably, the study unveils an intriguing aspect of medication tolerability, revealing its potential influence on stroke incidence. Older adults reporting minimal medication side effects demonstrated a lower likelihood of stroke, illustrating the importance of medication tolerability in sustaining adherence and subsequently (open full item for complete abstract)

Committee: Carolyn Harmon Still (Committee Chair); Nicholas Schiltz (Committee Member); Elliane Irani (Committee Member); Richard Josephson (Committee Member) Subjects: Aging; Medicine; Nursing

MS, University of Cincinnati, 2021, Allied Health Sciences: Nutrition

Background: The prevalence of hypertension (HTN) and elevated blood pressure (BP) in adolescents is a growing health concern. Lifestyle modifications including diet and exercise are the first line approach for adolescents with elevated BP. It is now recommended that clinicians provide advice on the Dietary Approaches to Stop Hypertension (DASH) diet at the time of diagnosis of elevated BP or HTN. Identifying eating patterns and certain food or food groups that promote satiety without significantly increasing overall energy intake is important for promoting healthful eating patterns, such as the DASH diet. Evidence regarding the relationship between satiety and the DASH diet (and target health outcomes) is minimal. This study sought to examine the relationship between satiety, as measured by Fullness Factor (FF), and change in DASH score, dietary intake, blood pressure measurements, and BMI in teens after a dietary intervention. Methods: This study is a secondary analysis of the DASH-4-Teens study conducted by Couch et al (2021). The parent study was a randomized clinical trial conducted at the Hypertension Center at Cincinnati Children's Hospital Medical Center that assessed the post-intervention and 18-month follow-up effects of a 6-month (DASH)-focused behavioral nutrition intervention on blood pressure (BP) and endothelial function in adolescents with elevated BP. For the secondary analysis, the relationship between the calculated post-intervention FF and change (baseline to 6-months post-intervention) in dietary quality, blood pressure, and BMI status was examined. Results: Per analysis of covariance (ANCOVA), post intervention FF was positively correlated to change in DASH score (p = 0.01) and dietary fiber intake (p = 0.04) and negatively correlated to change in saturated fat intake (p = 0.03). There were negative trends observed between FF and change in energy intake (p = 0.10) and change in total fat intake (p = 0.06). A positive trend observed betwee (open full item for complete abstract)

Committee: Abigail Peairs Ph.D. (Committee Chair); Sarah Couch Ph.D. (Committee Member) Subjects: Nutrition

Doctor of Nursing Practice, Mount St. Joseph University , 2021, Department of Nursing

Remote home blood pressure (BP) monitoring has the potential to improve patient engagement and adherence with the prescribed treatment plan for managing hypertension. This DNP project examined the effects of daily remote BP measurement using transmission of biometric data through a Bluetooth-equipped device paired to participants' smartphones. Twelve adults, with an age range of 37 to 69 years, completed four weeks of daily BP measurements and communicated via text, telephone call, or video visit with care team members to discuss the plan of care and address any concerns. A Wilcoxon signed-ranks test was performed to determine the magnitude of difference between the week 1 and week 4 systolic and diastolic BP measurements. The results revealed Week 4 systolic BPs (M = 127, SD = 12.48) were significantly lower than the Week 1 systolic BPs (M = 136, SD = 12.48), W = -2, p = .004 and the Week 4 diastolic BPs (M = 82, SD = 10.97) were significantly lower than the Week 1 diastolic BPs (M = 89, SD = 9.92), W = -4, p = .006. This average systolic decrease of 9 mmHg and average diastolic decrease of 7 mmHg indicated success in lowering BP within a four-week timeframe. The clinical management of a chronic condition such as hypertension is a long-term process, but the findings of this DNP project supported the empirical evidence showing that remote BP monitoring improves patient outcomes.

Committee: Stefanie Hiltz DNP (Advisor) Subjects: Health Care; Nursing

Master of Science (MS), Wright State University, 2020, Pharmacology and Toxicology

Hypertension, also known as high blood pressure, is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. It can lead to severe health complications and increase the risk of heart disease, stroke, and sometimes death. Perivascular adipose tissue (PVAT) is known as the adipose tissue (AT) surrounding all the blood vessels and plays a critical role in the pathogenesis of the vascular disease. In vascular pathologies, PVAT increases in volume and becomes dysfunctional, with altered cellular composition and molecular characteristics. Macrophages have been found to accumulate in PVAT during hypertension, which might be involved in the inflammation of hypertension. Inflammation has been shown to play an important role in hypertension; however, the exact mechanisms by which the activated immune cells partly lead to the development and maintenance of hypertension remain to be elucidated. The objective of this study is to determine the role of exercise in the inflammation of AT and PVAT by modulating the polarization of macrophages in hypertensive mice. Renin transgenic (R+) mice have been used as a hypertensive mice model. The PVAT, AT, and plasma samples were collected for the analysis of inflammatory cytokines, macrophages isolation, and polarization. The release of cytokines from AT and PVAT was determined by ELISA and the release of cytokines from plasma was determined by bio plex cytokine analysis. Our ELISA results did not show the changes of exercise on the release of cytokines in AT but could decrease the pro-inflammatory cytokines in PVAT. While our flow cytometry results showed that exercise affected the macrophage polarization in adipose tissue but not in PVAT. Cytokine analysis of plasma samples showed a decrease in pro-inflammatory cytokines IFN-g and IL-6, as well as anti-inflammatory cytokines IL-4 and IL-13, while an increase in IL-10 was noted, which might be related to effects of exercise by alleviating t (open full item for complete abstract)

Committee: Ji C. Bihl M.D., Ph.D. (Advisor); Yanfang Chen M.D., Ph.D. (Committee Member); Ravi P. Sahu Ph.D. (Committee Member) Subjects: Pharmacology; Toxicology

Doctor of Philosophy (PhD), University of Toledo, 2020, Biomedical Sciences (Molecular Medicine)

Hypertension is a complex polygenic trait influenced by multiple genetic and environmental factors. However, the genetic factors and the molecular mechanism by which they influence hypertension is not completely understood. Our laboratory is currently focusing on understanding the physiological and molecular aspects of two candidate genes for hypertension; Regulated Endocrine Specific Protein 18 (Resp18) and Chicken Ovalbumin Upstream Promoter Transcription Factor II (Coup-TFII). Previously, we have shown that a targeted disruption of Resp18 locus in Dahl Salt Sensitive (SS) rats (Resp18mutant) resulted in higher blood pressure (BP), increased renal fibrosis, urinary protein excretion, and decreased mean survival time on a long term (6-week) exposure to 2% high salt (HS) diet. To further our investigations, we tested the vascular reactivity in mesenteric arteries and glomerular filtration rate (GFR) by using FITC-sinistrin clearance measured by NIC- transdermal device. Through our study, we found that the Resp18mutant rats exhibited vascular dysfunction, as evidenced by a decrease in vasorelaxation in response to SNP and ACH. Furthermore, we found that Resp18mutant rats demonstrated a decrease in GFR. Furthermore, dopaminergic agonists decrease the expression of Resp18, whereas dopaminergic antagonists increase its expression suggesting a molecular link between Resp18 and dopamine. Hence, we are interested in testing the renal dopaminergic pathway in the kidney and renal proximal tubule (RPT) cells isolated from Resp18mutant and SS rats. Dopamine levels in the renal cortical specimens obtained from Resp18mutant rats were significantly decreased along with a decrease in D1-like dopamine receptors (D1R & D5R) expression in the kidney. Upon urine analysis and dopamine release assay in RPT cells, we observed that the Resp18mutant rats secrete an increased amount of dopamine compared to the SS rats. Based on the prominent kidney injury phenotype, we tested the hypothesis (open full item for complete abstract)

Committee: Sivarajan Kumarasamy (Committee Chair); Edwin Sanchez (Committee Member); Guillermo Vazquez (Committee Member); Beata Lecka-Czernik (Committee Member); Jiang Tian (Committee Member) Subjects: Biomedical Research

Doctor of Philosophy, Case Western Reserve University, 2020, Nursing

Incidence of pregnancy-induced hypertension (PIH) and gestational diabetes (GDM) are expected to rise. Given the adverse outcomes associated with PIH and GDM (preterm birth, cardiovascular disease, type two diabetes, and maternal or infant death) tools are needed to prevent the development of PIH and GDM. The key to preventing PIH and GDM may lie in elucidating the inflammation pathway in pregnancy. The purposes of the longitudinal correlational study were to describe 1) inflammation levels (C-reactive protein [CRP]) and 2) changes in inflammation levels between 12-16 (Time One) and 32-26 (Time Two) weeks gestation while 3) accounting for known determinates of inflammation: LPA genotype, lipoprotein (a) levels, physical activity, fat mass, and stress, and 4) determine the relationships among inflammation levels, determinants of inflammation, and maternal/ infant outcomes at birth. Forty-seven predominantly White and highly educated pregnant women were studied. CRP levels significantly decreased from T1 to T2. Physical activity, stress, fat mass, LPA genotype and lipoprotein (a) levels were not correlated with CRP in early or late pregnancy. PIH was significantly correlated with T1 CRP, T2 percent body fat, and delta CRP, GDM was significantly correlated with blood glucose and gestational age at birth. Gestational age at birth was correlated with stress at T1 and T2 and blood glucose was correlated with T1 CRP. Elevated inflammation levels appear to be present in early pregnancy for those who develop PIH or GDM and lifestyle behaviors that are related to maternal and infant outcomes offer potential intervention targets.

Committee: Susan Ludington (Committee Chair); Carol Musil (Committee Member); Rebecca Darrah (Committee Member); Patrick Catalano (Committee Member) Subjects: Nursing

Master of Science in Renewable and Clean Energy Engineering (MSRCE), Wright State University, 2020, Renewable and Clean Energy

Calcific aortic valve disease (CAVD), the most common valvular heart disorder, is associated with complications such as stroke, heart attack, aortic aneurysm, left ventricular hypertrophy, and ultimately death. While hypertension has been identified as a major risk factor for CAVD, the mechanisms by which it may promote calcification are still unknown. Given the sensitivity of valvular tissue to mechanical stress alterations, the hemodynamic abnormalities linked to hypertension may play a role in the development of CAVD. Further, the effects of hypertension on the left ventricular functionality and coronary flow resistance remain largely uninvestigated. Hence, the objectives of this thesis were 1.) to quantify computationally AV hemodynamics and regional leaflet mechanical stresses under normotensive, prehypertensive and stage-1 hypertensive conditions using Fluid- Structure interaction modeling, and 2.) characterize the effect of hypertensive conditions on ventricular workload and coronary flow resistance. This study will provide insights on the mechano-etiology of CAVD in hypertensive patients as well as the ventricular functionality and coronary flow under hypertension.

Committee: Philippe Sucosky Ph.D. (Advisor); Zifeng Yang Ph.D. (Committee Member); George P. Huang Ph.D. (Committee Member) Subjects: Biomechanics; Biomedical Engineering; Biomedical Research; Mechanical Engineering