Given the presumed importance of cardiovascular reactivity and the role of anger in the development of hypertension and coronary heart disease, this study is the first to jointly examine three related areas (i.e. gender effects, anger direction preference, and opportunity/no opportunity to aggress following an anger Inducing situation). The present study tested the following hypotheses: a) that cardiovascular reactivity would vary as a function of subjects' gender and direction preference; b) that the rate of cardiovascular recovery would vary as a function of anger direction preference and opportunity/no opportunity to aggress; c) that the subjective feelings of anger after harassment would vary as a function of gender, anger direction preference, and opportunity/no opportunity to aggress; and d) that the evaluation of experimenter's competency and performance would vary as a function of anger preference. 56 females and 49 males executed a math task while being harassed for "poor performance". Next, they were randomly assigned to either write a negative evaluation of the frustrator or to copy a neutral paragraph and then to circle some letters in another paragraph. Heart rate and blood pressure were measured intermittently throughout. Subjects' preferred mode of anger expression (i.e. anger-in versus anger-out) had been previously assessed and cross validated by self as well as peer evaluations. Results indicated that gender was a better predictor than anger direction preference for cardiovascular reactivity to harassment. Complex patterns of recovery were detected with Intriguing sex differences. Results on male diastolic recovery were consistent with a matching hypothesis of anger direction preference but only for anger-out males. In addition, subjective anger for males was related to opportunity/no opportunity conditions, whereas females did not show such a relationship. Female anger-ln's showed quicker systolic recovery than anger-out's. Lastly, the evaluation of experimenter's competency and performance did not vary as a function of anger preference. Therapeutic implications of the findings within the context of anger control as well as trends for future research are discussed. / Arts, Faculty of / Psychology, Department of / Graduate

Until now, the role of cyclin dependent kinase 5 (CDK5) in cardiac pathophysiology has not been explored. While CDK5 has been well studied in the neuroscience/Alzheimer’s field as a cyclin-independent kinase, there is currently no investigation into the cardiac-specific role of CDK5. Recently, it was established that inhibition of CDK5 in stem cell derived cardiomyocytes from individuals with Timothy Syndrome (TS) rescued the delayed inactivation phenotype; TS is a fatal genetic long QT syndrome (LQTS) caused by delayed inactivation of the L-type voltage gated Ca2+channel CaV1.2. While it is evident that CDK5 plays an important role in regulating CaV1.2 function, its role in cardiac tissue remains to be elucidated. To determine whether CDK5 is essential for cardiac function, two separate mouse models were established—a cardiac-deficient Cdk5 mouse model (Cdk5 flox x αMHC-MerCreMer+) and a Cdk5 activation mouse model via overexpression of Cdk5’s known activator, p35 (Cdk5r1/p35 OE x αMHC-MerCreMer+). Immediately after spatiotemporal induction of deficiency/activation of Cdk5 in adult mice, echocardiography, histology and proteomic analysis were performed to examine effects on cardiac structure and function. Analysis of cardiac function and morphology in Cdk5 deficient mice revealed severe systolic dysfunction and a dilated cardiomyopathy-like phenotype. These results were further validated by a pathway analysis of quantified global proteome changes. Conversely, mice with an activation of Cdk5 displayed only minor changes in cardiac function with a modest reduction in fractional shortening and ejection fraction. Notably, these mice did not have any significant changes in cardiac chamber morphology, nor any significant changes to their global proteome. Interestingly, however, phosphoproteomic analysis revealed over 3,000 differentially phosphorylated proteins. Pathway and gene ontology analysis of proteome changes revealed significant hits related to cell adhesion. Evidence for the extensively studied role of CDK5 in the brain has demonstrated a critical role for CDK5 kinase activity in the regulation of cell adhesion. Alterations in cell adhesion are observed in a number of cardiac pathologies including heart failure and dilated cardiomyopathy; it is therefore plausible that CDK5 potentially regulates cardiac function via cell adhesion mechanisms. A comparison of the phospho-proteome acutely after Cdk5 depletion vs the phospho-proteome acutely after Cdk5 activation, allowed for the identification of a novel cardiac-specific Cdk5 substrate, beta taxilin (Txlnb). Validation of this potential phospho-substrate with an in situ proximity ligation assay demonstrated the co-localization of Cdk5-Txlnb in wildtype mouse cardiac tissue sections. When looking at co-localization in Cdk5 deficient tissue sections, no signals were observed. Lastly, our lab obtained donor cardiac tissue samples from individuals who passed away due to either heart failure or non-cardiac causes (serving as control cardiac tissue). Analysis of cardiac tissue samples revealed a significant increase in both CDK5 and p35 expression in heart failure samples. Dysregulation of phosphorylation has been implicated in cardiac dysfunction, with known contribution to contractile failure and a number of cardiac pathologies including cardiomyopathies. These findings further support a role for CDK5 in cardiac function. In conclusion, it appears that CDK5 is imperative for the maintenance of healthy cardiac function. Cardiac-specific homozygous and heterozygous Cdk5 deficiency revealed severe systolic dysfunction along with a dilated cardiomyopathy-like phenotype. While the effects of Cdk5 activation in the heart need to be further investigated, initial findings report significant downstream effects on the phosphorylation of a number of proteins, including Txlnb. Moreover, Txlnb was identified as a potential novel cardiac-specific substrate of Cdk5. The importance of identifying a role for CDK5 in the heart extends beyond this study. CDK inhibitors have been at the forefront of drug development for cancer therapeutics and immunotherapy. While modulation of CDK5 activity may be beneficial in one physiological system, it may prove deleterious in another. It is therefore imperative that the full range of molecular and physiological roles of each CDK be fully elucidated prior to therapeutic application. Furthermore, outcomes from this study have the potential to be translational for drug discovery and the development of new therapeutic avenues for heart disease.

An experiment was conducted to investigate three different treatment strategies in the rehabilitation of coronary artery bypass graft (CABG) patients. Fifteen CABG patients were randomly assigned to one of three training groups: an outpatient cardiac rehabilitation exercise group (which met three times per week for three months); a second group which participated in weekly stress management training for seven weeks in addition to the cardiac rehabilitation exercise sessions; and a third group which participated in a weekly discussion on social support in addition to the exercise sessions. The groups were compared (pre- and post training) on the following physiological dependent measures: systolic and diastolic blood pressure, mean heart rate, cholesterol, triglycerides, high density lipoproteins, and the cholesterol/high density lipoprotein ratio. Psychological self-report measures included: the Beck Depression Inventory, the Spielberger State/Trait Anxiety Index, the Jenkins Activity Survey, and the Hassles and Uplifts Questionnaire. The Structured Interview was given to each patient prior to training only. It was predicted that the group trained in stress management and exercise would show the most positive changes on physiological and psychological dependent measures compared to the other two groups. The results indicated no significant pre/post differences on any of the variables for any of the groups. Thus, the additional components of stress management training and the social support discussion group did not appear to effect more positive change in those patients compared to those who participated in exercise only. Findings may have been influenced by several factors including a small N in each group and large within group variability. Suggestions for future research are discussed.

Cardiovascular diseases are the leading cause of morbidity and mortality worldwide. Congenital heart disease (CHD) is a risk factor for premature cardiovascular complications. Great advances have occurred in the past years leading to the identification of several genes essential for proper cardiac formation such as GATA4/5/6 mutated in some individuals with CHD. GATA6 is a zinc finger transcription factor whose presence is crucial for early embryonic development. GATA6 is expressed in many cell types of the heart including myocardial, endocardial, neural crest, and vascular smooth muscle. In human, mutations in GATA6 result in variable cardiac phenotypes. The objective of this thesis was to determine the roles that GATA6 play in the different cell types of the heart and to elucidate the molecular basis of the cardiac defects associated with Gata6 haploinsufficiency. For this, a combination of cell and molecular techniques were used in vitro and in vivo. First, we show that Gata6 heterozygozity leads to RL-type bicuspid aortic valve (BAV)- the most common CHD affecting 2% of the population. GATA6-dependent BAV is the result of disruption of valve remodeling and extracellular matrix composition in Gata6 haploinsufficient mice. Cell-specific inactivation of one Gata6 allele from Isl-1 positive cells, but not from endothelial or neural crest cells, recapitulates the phenotype of Gata6 heterozygous mice revealing an essential role for GATA6 in secondary heart field myocytes during valvulogenesis. We further uncovered a role for GATA6 as an important regulator of the cardiac conduction system and revealed that GATA6 expression regulates the activity of the cardiac pacemaker. GATA6 exerts its role via regulation of the cross-talk among the different cell types of the SAN. Lastly, some CHDs are characterized by abnormalities of both the limbs and the heart such as the Holt Oram syndrome (caused by mutation in TBX5 transcription factor). The molecular basis for limb-heart defects remain poorly understood. In the course of this work, we discovered that Gata6 haploinsufficiency resulted in a partially penetrant polysyndactyly (extra digits fused together) phenotype. Together, the data provide novel molecular and cellular insight into GATA6 role in normal and pathologic heat development. Our results also suggest that GATA6 should be added to the list of genes whose mutations are potentially associated with heart and limb abnormalities. Better knowledge of the molecular basis of CHD is a prerequisite for the development of diagnostic and therapeutic strategies to improve care of individuals with congenital heart disease.

Nurses constitute the foundation of America's healthcare system, and their roles are central to effective patient care in a variety of settings. Nurses are trained to give care and comfort to others. The purpose of this qualitative exploratory case study is to explore the experiences of registered nurses who take care of critically ill patients in telemetry units to gain a deeper understanding of how these telemetry nurses describe the self-care practices they employ to deal with the high demands of their job. There exists a need to set in motion plans to preserve a healthy nursing workforce to care for America's aging population, now and in the future. Therefore, studying the well-being of telemetry nurses and how they care for themselves is crucial. Very little is known about how telemetry nurses manage their well-being through self-care practices. However, Duffy (2015) suggests this is important because "the secret of caring for patients is caring for our caregivers" (p. 5). The intent of the study is to gain a deeper understanding of the self-care practices employed by telemetry nurses and the real or perceived effectiveness of such practices. A deeper understanding of the phenomenon of “self-care practices” among this group of nurses may provide findings that allow nurse leaders, educators, regulatory agencies, and policy makers to design and implement the appropriate training, education, and environment needed to sustain a healthy telemetry nursing workforce. The major finding from this study is this group of telemetry nurses’ self-care activity was primarily “Spirituality”. Thus, in relation to the Six Dimensions Wellness model, more attention is needed in the five other components as an indicator they are fully practicing self-care.

Thesis (M.Sc. (Chemistry)) -- University of Limpopo, 2022 / Heart and Stroke Foundation South Africa (HSFSA) reports that about 17.3% of deaths in the country are associated with heart-related diseases and this rate is expected to increase to 41% by the year 2030. This severe increase in death cases is related to diseases caused by consumption of meat (i.e., pork, fish, red meat, and poultry) with high levels of hypoxanthine. Therefore, this raises the need to investigate and detect hypoxanthine levels in the meat. This study aimed at developing a highly stable and sensitive biosensor for the detection of hypoxanthine in fish meat using the glassy carbon electrode (GCE) modified with carbon nanocomposites materials (consisting of metal oxides doped multi-walled carbon nanotubes (MO-MWCNTs) that are treated with amine groups) and an enzyme, xanthine oxidase (XOD) as a catalyst. The sol gel method was used to prepare the metal oxides including zinc oxide (ZnO), zirconium dioxide (ZrO2), manganese (MnO2), cobalt oxide (Co3O4), and titanium dioxide (TiO2). The in-situ method of functionalisation of MWCNTs was employed to increase their current outputs/sensitivity using selected amines, namely, methylenediamine, hydrazine, ethylenediamine (EDA), and triethylenetetramine (TETA). The electrochemical properties of the metal oxides and amine functionalised MWCNTs were studied using both cyclic and differential pulse voltammetry. Fourier transform infrared spectroscopy (FTIR) confirmed the presence of carboxyl (COOH), hydroxyl (OH), and amino (NH2) groups on the surface of the modified MWCNTs; as well as formation of stretching vibrations which appear at lower wavelengths due to the metallic species within the nanocomposite. Thermal gravimetric analyser (TGA) was employed to determine the thermal stability of the nanocomposite. Scanning electron microscopy (SEM) was used to confirm the composite structure and correct deposition of the metal oxides on the walls of MWCNTs. XRD was used to confirm correct structure formation, the crystallinity, and the purity of the nanocomposite. Optimum conditions of the developed biosensor were determined, and the application of the developed biosensor was undertaken on fish meat bought at the local supermarket using the Cyclic and Differential pulse voltammetric techniques. vi Two highly electrochemical metal oxides among others were TiO2 and Co3O4. The modified MWCNTs containing TETA possess good electrochemical properties with improved sensitivity and selectivity towards hypoxanthine. The presence of metal oxides on MWCNTs and their treatments with amines as confirmed by techniques such as TGA, SEM, XRD, and FTIR have provided a suitable matrix for the immobilisation of the enzyme, namely, xanthine oxidase at 0.5 unit (U). TGA results showed that the unmodified MWCNTs decompose at around 600 0C, but when they are modified with acids and amine decomposition starts at 230 0C, proving that functionalisation of MWCNTs tempers with their thermal stability. Based on the SEM morphological results, attachment of the amines and metal oxides on MWCNTs was seen at x60 000 magnification. Morphology of acid treated MWCNTs appeared thinner, revealing that acids tends to deteriorate the MWCNTs, while the amino treated MWCNTs appeared well modified with less damage on the MWCNTs. XRD confirmed the successful purification of MWCNTs with the intense diffraction peak at 260 that can be assigned to the (002) reflection of graphite. The strong diffraction peak at 250o and a broad peak at 450 indicate that the titania nanoparticles are pure and in the anatase phase. They also show successful deposition of the titanium dioxide onto the surface of the MWCNTs. However, on the formation of cobalt oxide two phases were observed which were CoO, and Co3O4, and on bimetallic nanocomposite (cobalt titanium oxide) also two phases were observed which were CoTiO3, and Co2TiO4. It was found that the sensor performs better at 25 oC at a pH of 7.5 in a phosphate buffer at concentration of 5 mM. The limit of detection of the biosensor was found to be 0.16 nM. The highly electroconductive electrode was XOD/3%Co2TiO4-MWCNTs-TETA/GCE, which was selected for analysis of fish meat. The biosensor has shown low interfering values with high stability, good reusability retaining 73.4% of its initial performance after 50 days of continuous study. The excellent results were obtained on fish meat analysis using cyclic and differential pulse voltammetry revealed that even meat which is deep frozen can also deteriorate as time passes by. Altogether, the findings from this study suggest that the developed biosensor is a reliable analytical tool for the determination of freshness of fish meat using hypoxanthine levels as a marker. / NRF Sasol Inzalo Foundation

One hundred and seventy male and female volunteers employed at Hubbell Lighting Inc., Christiansburg, Virginia were studied to determine the effectiveness of two alternative educational strategies for lowering elevated blood cholesterol by modifying the diet. Initially three hundred and twenty-eight employees were weighed and tested for elevated total blood cholesterol via a finger-stick procedure using a Reflotron. Two hundred of these employees had elevated total blood cholesterol readings (2: 200 mg/dl) and were invited to participate in the study. The one hundred and seventy employees who consented to participate were divided into plant and office populations and then each of these two subpopulations was then randomized by sex into one of three experimental groups: individuals receiving worksite classes, those who received information on diet and blood cholesterol mailed to their homes, or a control group. Prior to the baseline blood cholesterol test, subjects completed and returned a pre-test questionnaire used to obtain demographic data and assess baseline knowledge, dietary practices and health-relevant attitudes such as self-efficacy, perceived susceptibility to heart disease, and perceived social support. Subjects also completed a three-day food record on the first and eighth week of the study as well as a post-test questionnaire identical to the pre-test questionnaire prior to the second blood cholesterol test which was performed during the tenth week of the study. No significant differences were observed over the experimental period in body weight. knowledge, dietary practices, and health relevant attitudes. Significant differences were observed for the dependent measure of change in blood cholesterol with a group and education level effect identified between subjects receiving worksite classes vs. the control group (p = .0284**) and subjects with only a grade school level education vs. all other education levels (p = .0021 **). Overall. subjects reduced total blood cholesterol levels by 18 mg/dl or 9% with the mean reduction for white and blue-collar groups receiving worksite classes (23 mg/dl or 11% and 19 mg/dl or 9%) significantly greater than the mean reduction for the control groups (13 mg/dl or 6% and 14 mg/dl or 7%). Subjects with only a grade school education reduced their cholesterol levels more than subjects at all other educational levels. The mean reduction in blood cholesterol for subjects receiving information mailed to the home about diet and blood cholesterol was less than the mean reduction for subjects in groups receiving the worksite classes. However. ANOV A revealed that there was no statistically significant difference between these two groups. Since, the mailed home approach is less costly for the employer, these findings suggest that while the two educational interventions may be similar in terms of effectiveness, the mailed home approach is more cost-effective. / Master of Science

In the present study, the contractility of isolated cardiac muscle obtained from normotensive and treated or untreated hypertensive rat hearts were investigated. The effects of inotropic agents were also explored • Some SHRs were subjected to chronic antihypertensive treatment. After their blood pressure had been lowered, positive and negative inotropic agents were used to study the papillary muscles. The effects of acidosis, increased extracellular calcium, hypoxia, and reoxygenation on the isolated papillary muscles obtained from their hearts were studied. The same was done for isolated cardiac muscles that were removed from WKYs and SHRs. Isoproterenol in the absence or presence of propranolol was also used to investigate the contractility of SHRs and WKYs. Clonidine, alpha-methyldopa, and verapamil all reduced the blood pressures of SHRs which were on chronic antihypertensive therapy. When propranolol was added to the muscle bath, the developed tension of the SHRs was significantly higher than that of the WKYs by 13.1% (p

Advances in genome editing, human induced pluripotent stem cells (iPSC), and cardiac tissue engineering have significantly improved the ability of in vitro models to model cardiac disease. The objective of this dissertation is to leverage cardiac tissue engineering to generate meaningful biological insights into human genetic cardiomyopathies. First, we studied a novel, de novo mutation in the filamin C (FLNC) gene which causes restrictive cardiomyopathy in a young patient. Using engineered cardiac tissues, we showed that this mutation causes a restrictive phenotype marked by increased passive tension and slowed contraction velocities. Complementing our engineered tissues, we used high-throughput calcium imaging to identify compounds which improved myocardial relaxation in mutant cardiomyocytes. These compounds improved function of mutant cardiac tissues, suggesting a potentially targetable pathway in the patient’s mutation. In another study, engineered cardiac tissues and stem cells were used to study BAG3, a dilated cardiomyopathy- related gene, in cardiac fibroblasts. BAG3-/- and wild-type iPSCs were differentiated to cardiac fibroblasts and cardiomyocytes. By generating fully isogenic cardiac tissues and altering cellular genotypes, we determined that the loss of BAG3 in cardiac fibroblasts was deleterious to cardiac tissue function despite genetically normal cardiomyocytes. Further work studying cardiac fibroblasts revealed a mechanistic function of BAG3 in regulating cardiac fibroblast extracellular matrix synthesis. Together, this work highlights the ability of cardiac tissues and stem cells to unravel the complexities of genetic heart disease.

Mutations in the gene encoding the nuclear lamina protein lamin A/C (LMNA) and the associated integral inner nuclear membrane protein emerin (EMD) give rise to similar disease phenotypes and are both classified as Emery-Dreifuss muscular dystrophy (EDMD). However, the connection between the function of these nuclear envelope proteins and disease phenotype remains elusive. Given the consistent manifestation of dilated cardiomyopathy in EDMD, my investigation focused on deciphering the roles of these nuclear envelope proteins in the heart. To better understand their functions, I generated a set of isogenic human induced pluripotent stem cell (iPSC) lines with either LMNA mutation causing lamin A/C haploinsufficiency or EMD mutation causing emerin deficiency. I differentiated these iPSCs into cardiomyocytes (iPSC-CMs) and obtained their RNA transcript and protein expression profiles. I found that both mutant lines exhibited significant overlap in transcriptome and proteome changes. Analyzing alterations at both RNA and protein levels shed light on the potential functional roles of lamin A/C and emerin in cardiomyocytes and pathogenic mechanisms. To better understand the cardiac defects caused by loss of lamin A/C. I generated mice lines with tissue-specific and temporally regulated knockout of Lmna in the heart. The mutant mice experienced lethality due to heart failure, regardless of whether Lmna was knocked out at the embryonic or mature adult heart. This demonstrates that lamin A/C has a vital role in the normal function of cardiomyocytes.