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Cardiovascular disease (CVD) risk behaviors, namely tobacco smoking, hazardous alcohol use, poor diet and sedentary behavior, are more prevalent among people living with HIV (PLWH) than the general population. Qualitative evidence shows that PLWH report adopting unhealthy behaviors as a means of coping with the stress of living with HIV, including the adverse physiological symptoms of HIV infection, the psychological stress of being aware of one’s HIV status, and the physiological and psychological impacts of being on HIV treatment. These observations suggest that being HIV-positive may have a causal influence on CVD risk behaviors and that these causal effects likely differ across stages of the HIV continuum. To date, few quantitative studies have been conducted to examine these causal relationships. The goal of this dissertation was to explore the effects of HIV continuum stage on CVD risk behaviors and assess several plausible stress-coping mechanisms, as motivated by established stress-coping theory. This dissertation consisted of three studies. First, a systematic review was conducted to examine the existing quantitative evidence for the causal effects of HIV continuum stage on CVD risk behaviors. Findings from this review revealed that being HIV-positive is associated with excess smoking and drinking, and that while receipt of a positive HIV diagnosis is associated with short-term improvements in some CVD risk behaviors, these improvements are unlikely to be maintained long-term. Overall, however, the existing studies suffer important methodological limitations, notably inadequate characterization of HIV continuum stage. The second study was an empirical analysis of patterns of self-reported CVD risk behaviors across the HIV continuum among a population-based sample of 4,061 adults aged 40 years and over living in rural Agincourt district in South Africa. Results showed no consistent evidence of an association between HIV continuum stage and hazardous alcohol use or sedentary behavior. However, higher prevalence of smoking was observed specifically among males who were HIV-positive and aware of their status but not on treatment, compared to those who were HIV-negative. There was no evidence of mediation by various measures of physiological and/or psychological stress. The third study was an analysis of whether perceived life expectancy (PLE) modifies the effects of HIV continuum stage on CVD risk behaviors. Observed associations were most prominent among individuals with low PLE and null among those with high PLE. Overall, this dissertation contributed to greater understanding of the relationship between CVD risk behaviors among HIV-infected persons across the HIV continuum. Findings did not support a stress-coping hypothesis; however, PLE was found to be a potentially useful indicator of individuals who are most likely to smoke in the presence of HIV. This dissertation also fills evidence gaps among older adults in sub-Saharan Africa, an under-studied population with high and increasing burdens of both HIV and CVD. As HIV-positive population survive longer on antiretroviral therapy and the prevention of age-related conditions becomes increasingly important, these findings may help inform future research and the development of CVD prevention interventions.

Cardiovascular risk factors have expanded to include personality and other psychological characteristics. Negative affect (NA) has a longstanding history in cardiovascular health, but the path by which NA leads to cardiovascular disease (CVD) is yet to be defined. The following study examined the relationship of high NA and low extroversion (EX) with physiological cardiovascular markers in a sample of non-medical, professional adults. Our results indicated that individuals high in NA and low in EX displayed a significantly lower platelet count and a significantly higher mean platelet volume. Individuals high in NA displayed a significantly lower cholesterol risk ratio, while individuals high in EX displayed significantly higher platelet counts. Personality was not significantly related to blood pressure, high or low density lipoproteins. Understanding the relationships among psychological variables and physiological markers will help clinical researchers design interventions that reduce the likelihood of CVD.

High-voltage activated calcium channels underlie many critical functions in excitable cells and their dysfunction has been implicated in a myriad of cardiovascular and neurological diseases. These channels are multimeric protein complexes composed of α1, β, and α2δ subunits; currently, all calcium channel blockers target either the pore-forming α1 or extracellular-facing α2δ auxiliary subunit. These pharmacological agents have been invaluable in delineating the individual function of each subunit within excitable cells that express multiple calcium channels. Yet, no current tool allows similar pharmacological dissection of individual cytosolic β subunits, preventing our understanding of how distinct β subunits affect the function of calcium channel complexes. Further, small-molecule calcium channel blockers are highly-valued therapeutics for certain conditions, yet their propensity for off-target effects precludes their use in other diseases. In certain applications, genetically-encoded calcium channel blockers may enable channel inhibition with greater tissue-precision and versatility than is achievable with small molecules. Previous work that found the family of RGK proteins powerfully inhibits high-voltage activated calcium channels in part via an association with the β subunit. However, the myriad functions of RGK proteins limit the utility of this approach. In this work, we circumvent this issue by isolating single-domain antibodies (nanobodies) that target the auxiliary CaVβ subunit. We then paired these nanobodies with the powerful enzymatic activity of the HECT domain E3 ubiquitin ligase Nedd4L, to selectively target the calcium channel for ubiquitination. We found this strategy effectively eliminated functional calcium channels from the surface of HEK293 cells, myocytes, and DRG neurons. This modular design permitted us to characterize a pan-β inhibitor (CaV-aβlator) in chapter 2 while refining the approach with a β1-selective channel inhibitor in chapter 3. In chapter 4 I demonstrate that it is possible to hijack the endogenous ubiquitin machinery of the cell by creating Divas: divalent nanobodies that are capable of recruiting endogenous Nedd4L to regulate the calcium channel. Finally, we demonstrate the potential for these genetically-encoded calcium inhibitors to be employed as therapeutic agents by targeting CaV-aβlator to sensory neurons in order to reduce the onset of neuropathic pain. Altogether, this work lays the foundation for nanobody-based genetically-encoded calcium channel inhibitors that have the potential to achieve superior precision in regards to molecular and tissue specificity.

An accumulating evidence-base indicates that internalizing mental health disorders in adulthood are causally associated with cardiovascular diseases (CVD) and type-2 diabetes (T2DM). It is plausible, however, that the relationship between mental and cardiometabolic ill-health becomes established long before adulthood, and that externalizing problems (the other central domain of common psychopathology) are also involved. These questions, as well as questions on the mechanisms that underlie the relationships, have been insufficiently investigated. The overarching goal of this dissertation was to expand current knowledge on how common mental health problems increase cardiometabolic risk over the life course. First, the prospective association between childhood internalizing (emotional problems) and externalizing problems (hyperactivity and conduct problems) with CVD and T2DM risk in adolescence was assessed in data from the Avon Longitudinal Study of Parents and Children (ALSPAC, N=7,730). Results showed that hyperactivity problems were associated with insulin resistance (high HOMA-IR); that hyperactivity and conduct problems were each associated with high triglyceride levels; and that emotional problems were inversely associated with high triglyceride levels. These results suggest that childhood externalizing problems are an early life risk factor for CVD and T2DM and that childhood internalizing problems are not a risk factor or, that risk in these children does not become apparent until after adolescence. Second, the mechanisms underlying the prospective association of childhood hyperactivity and conduct problems with high levels of triglycerides in adolescence were investigated using causal mediation methods. Results showed that despite being associated with hyperactivity and with conduct problems, body mass index and lifestyle health behaviors including sleep, diet, physical activity, alcohol, and smoking, together these variables, as measured, mediated only 19.6 % and 19.3% of the associations of hyperactivity and conduct problems with triglycerides, respectively. These results would suggest that mechanisms other than body adiposity and unhealthy behaviors are also involved and that those mechanisms have a larger role in mediating these relationships. Alternatively, It is possible that the observed small role of health behaviors is due to error in measurement and therefore improving measurements for health behaviors should be a central focus of future work. Third and last, a systematic review of the literature on the relationship between childhood externalizing problems with CVD and T2DM risk was conducted. Studies were graded for propensity to bias. Evidence was summarized and assessed for consistency. Results strongly supported positive associations of externalizing problems with insulin resistance, T2DM, and with increased blood lipids among children and adolescents. Evidence suggested that associations are at least partly independent of body adiposity. Evidence provided mix support for the associations with T2DM and blood lipids in adults and with other outcomes in children or adults. Studies in children tended to be cross-sectional and to use valid and reliable assessment methods, whereas studies of adults tended to be prospective and to rely on less-valid, less reliable assessment methods. These results warrant more research, specifically prospective studies that track children into young adulthood, that employ well-validated measures of externalizing behaviors, that rely on repeated assessments of T2DM and CVD risk throughout follow-up, and that investigate mechanisms other than body adiposity and health behaviors. Overall, this dissertation has found that childhood externalizing problems are prospectively associated with elevated CVD and T2DM risk, specifically with elevated risk of increased levels of blood lipids and insulin resistance. Unlike studies in adults, this dissertation does not support a role of internalizing problems as risk factors. Among children with externalizing problems, risk becomes evident before adolescence and appears to be largely driven by pathways independent of unhealthy behaviors and body adiposity. Implications of this research’s findings for health practice were proposed. This dissertation identified several gaps and methodological shortcoming in the extant literature. Recommendations were made for future research, including fundamental next questions to investigate, and study designs and methodologies that are best suited to tackle those questions.

The events of cardiac surgery combined with moderate hypothermia hemodilution perfusion and postoperative respiratory care provide the stimuli for the alteration of K+ levels in red blood cells, plasma, and urine. The purpose of this study was to measure the deviations from normal potassium ion concentrations in an attempt to understand the physiological processes involved.

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Climate change is already harming public health through warmer, more erratic weather and many downstream consequences. Research can support climate change adaptation by characterizing climate-related exposures, identifying vulnerable populations, and identifying effective interventions. Furthermore, the main source of greenhouse gas emissions, fossil fuel combustion, also produces air pollutants such as fine particulate matter (PM2.5) that directly harm human health. In this dissertation my colleagues and I have examined the effects of short-term temperature exposure on myocardial infarction and stroke to inform adaption (Chapters 1 to 3) and leveraged multiple exposure models to estimate annual PM2.5 concentrations and quantify uncertainty (Chapter 4). To examine the effects of short-term temperature exposure, we conducted case-crossover analyses using an administrative dataset of hospitalizations in New York State. For PM2.5 prediction and uncertainty characterization, we applied a flexible ensemble approach to leverage seven already-developed PM2.5 models. Overall, we found that warmer hourly temperatures and greater daily temperature variability increased the risk of ischemic events, and lower hourly temperatures increased the risk of hemorrhagic stroke. The ensemble model showed high predictive accuracy, demonstrating the strength of this approach, and we observed greatest uncertainty in the Pacific Northwest and southeast coast. The methods applied in this dissertation can be applied to other exposures and in different settings to further quantify the risks of climate impacts and improve air pollution assessment. Future research should examine the joint impacts of multiple weather factors, strategies to protect people in group housing from extreme weather, measurements and models to reduce uncertainty of air pollution exposures, and propagate exposure uncertainty into health models. However, the need for further research should not delay climate action today.

Increasing complexity in critical coronary care nursing and advancements in medical technology have resulted in the need for clearly articulated competencies consistent with current practice. This need has been identified both in the literature and in practice. The problem addressed in this study was to determine what competencies, beyond basic nursing preparation, are essential for the beginning level coronary care nurse in order to provide safe nursing practice. A three-round modified Delphi Technique was used to elicit the authority opinions of 14 experienced clinical nurse specialists currently practicing in the coronary care unit. The nurse experts identified and verified the essential cognitive and technical skills required for nurses at the beginning level of practice in coronary care units. Nine domains and 63 competency statements were generated and refined. All were designed to be learner oriented, behaviorally described, and measurable. Implications are discussed for the design of an orientation program for beginning level coronary care nurses as well as implications for further research. / Ed. D.

Forty-six employees of an industrial bearing plant volunteered to participate in a workplace hypertension program. The purpose of this study was to lower hypertensive employees' blood pressure by having plant supervisors educate the employee in an eight-week hypertension program on his or her high blood pressure. This was done in an effort to aid employees in the management of their blood pressure, as well as to provide a source of emotional support within the plant. Subjects were randomly assigned to an experimental or control group. Supervisors of each hypertensive subject were given educational instruction on high blood pressure and variables related to hypertension. Supervisors also were given specific weekly assignments to convey to their subjects. Pretest and posttest measurements were made on blood pressure and knowledge concerning blood pressure. At the end of the eight-week intervention, a significant decrease in systolic blood pressure was seen in the experimental group with a 16 mm.Hg. drop (p < .05). There was no significant difference (p > .05) between the two groups on diastolic pressures, with both groups dropping to within the guidelines recommended by the American Heart Association (1987). Subjects in the experimental group scored higher on their knowledge of blood pressure than did subjects in the control group (p < .01). The results of this study indicate that a hypertensive educational intervention program may produce positive changes in employee blood pressure responses. / Master of Science