Inflammation contributes to the etiology of type 2 diabetes (T2D) and cardiovascular disease (CVD). Therefore, it is of interest to investigate how diet relates to plasma inflammatory proteins, particularly whole grain and fibre intakes, as these factors have been associated with lower CVD and T2D risk. Only a limited number of observational studies have examined these relationships. The objective of this study was to investigate the cross-sectional relationships of whole and refined grain and dietary fibre intakes with plasma inflammatory proteins. There was a strong inverse relationship between whole grain intake and plasminogen activator inhibitor type 1 (PAI-1) (β =-0.102; SE=0.038; p=0.0077), and a positive relationship between refined grain intake and PAI-1 (β=0.076; SE=0.034; p=0.0251). Additionally, dietary fibre was related to lower concentrations of C-reactive protein (β=-0.034; SE=0.010; p=0.0008) and fibrinogen (β=-1.207; SE=0.505; p=0.0171). This research suggests that whole and refined grain and fibre intakes may influence inflammatory protein concentrations.

Objectives: Research literature points to a range of “factors” that are associated with return to work outcomes but little understanding of the experience of workers, the strategies used to adapt, how work shapes and influences adjustment, and the trajectories that describe their return to work experience. The aim of this qualitative, workplace-based study was to characterize workers readaptation to the workplace and develop a substantive framework for return to work following disabling cardiac illness. Methods: The study used a concurrent, nested, mixed methods approach, using grounded theory to inform the sampling and analysis framework. Participant workers were 12 males having suffered occupational disability owing to cardiac illness and returning to work at a large auto manufacturing plant. Participants were purposefully sampled for a range of disease and disability experiences as well as a range of work roles in the plant. Data were derived from semi-structured in-depth interviews, standardized questionnaire measures of health-related quality of life and work limitations, observations within the plant, and extensive field notes and memos. Longitudinal information was obtained through follow-up interviews over a two to ten month period. Results: Participants had a range of illness impacts and representations and fulfilled diverse roles in the plant including assembly jobs and trade work. Thematic analysis revealed that participants used adaptive strategies including changing mindset in relation to work, building physical capacity and efficiency, managing relationships and work schedules, and using supports in the plant. Thematic analysis highlighted the importance of the nature of work, the quality of work relationships, organizational practices around accommodation and supports in the workplace including occupational health support. Conclusions: Worker adaptation following disabling cardiac illness involved a process of self-regulation including elements of illness and work representations, deployment of adaptive strategies to compensate for ongoing impairments, self-monitoring, goal setting and adaptive selection of work activities. Work demands, relationships and structures provide a range of possibility for self-regulation and quality of life. Implications for practice for work and health researchers and professionals as well as potential linkages to theory are discussed.

Inflammation contributes to the etiology of type 2 diabetes (T2D) and cardiovascular disease (CVD). Therefore, it is of interest to investigate how diet relates to plasma inflammatory proteins, particularly whole grain and fibre intakes, as these factors have been associated with lower CVD and T2D risk. Only a limited number of observational studies have examined these relationships. The objective of this study was to investigate the cross-sectional relationships of whole and refined grain and dietary fibre intakes with plasma inflammatory proteins. There was a strong inverse relationship between whole grain intake and plasminogen activator inhibitor type 1 (PAI-1) (β =-0.102; SE=0.038; p=0.0077), and a positive relationship between refined grain intake and PAI-1 (β=0.076; SE=0.034; p=0.0251). Additionally, dietary fibre was related to lower concentrations of C-reactive protein (β=-0.034; SE=0.010; p=0.0008) and fibrinogen (β=-1.207; SE=0.505; p=0.0171). This research suggests that whole and refined grain and fibre intakes may influence inflammatory protein concentrations.

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This dissertation focuses on a novel approach for characterizing the mechanical behavior of an elastic body. In particular, we develop a mathematical tool for the estimation of residual stress field in an elastic body that has mechanical properties similar to that of the arterial wall, by making use of intravascular ultrasound (IVUS) imaging techniques. This study is a preliminary step towards understanding the progression of a cardiovascular disease called atherosclerosis using ultrasound technology. It is known that residual stresses play a significant role in determining the overall stress distribution in soft tissues. The main part of this work deals with developing a nonlinear inverse spectral technique that allows one to accurately compute the residual stresses in soft tissues. Unlike most conventional experimental, both in vivo and in vitro, and theoretical techniques to characterize residual stresses in soft tissues, the proposed method makes fundamental use of the finite strain non- linear response of the material to a quasi-static harmonic loading. The arterial wall is modeled as a nonlinear, isotropic, slightly compressible elastic body. A boundary value problem is formulated for the residually stressed arterial wall, the boundary of which is subjected to a constant blood pressure, and then an idealized model for the IVUS interrogation is constructed by superimposing small amplitude time harmonic infinitesimal vibrations on large deformations via an asymptotic construction of its solution. We then use a semi-inverse approach to study the model for a specific class of deformations. The analysis leads us to a system of second order differential equations with homogeneous boundary conditions of Sturm-Liouville type. By making use of the classical theory of inverse Sturm-Liouville problems, and root finding and optimization techniques, we then develop several inverse spectral algorithms to approximate the residual stress distribution in the arterial wall, given the first few eigenfrequencies of several induced blood pressures.

Metallic implants called stents are an important part of the treatment of coronary heart disease. While clinical trials are excellent indicators of outcomes, microscopic evaluation of the host tissue response to the implant is required to assess their safety and efficacy. However, the evaluation of human autopsy tissue containing metal implants presents unique challenges in order to obtain the best results. We used integrated microscopy techniques incorporating microCT and novel plastic histology techniques to demonstrate its effectiveness on human stented vessels obtained at autopsy. A total of seven cases are demonstrated where our analysis techniques were able to elucidate the pathogenesis of the host response and identify the specific cause of the complications with the stented vessel seen clinically. These techniques are more cost effective and efficient than other techniques currently in use, which could enable them to be used as part of routine autopsy evaluation. The expansion of the pool of stented vessels able to be analyzed to include the often overlooked large population of autopsy cases could provide an enormous amount of data to guide future clinical trials and improve patient care.

ABSTRACT Introduction: Renal transplant recipients (RTR) with abnormal glucose tolerance (AGT) are at an increased risk of graft failure and cardiovascular disease (CVD). CVD is the major cause of death in RTR. Whilst there are numerous known risk factors for AGT in RTR, it is unknown whether lifestyle factors are found in the presence or play a role in the development of AGT in RTR. The nutritional status of RTR in an Australian population has also not been extensively investigated. Investigation into these areas could help identify modifiable areas for change in the RTR population. Multidisciplinary lifestyle modification, including diet and physical activity (PA) advice from a dietitian, may help reduce modifiable risk factors for CVD in RTR with AGT. Aims: The principle aims of this thesis are to; 1) assess the incidence of obesity and central obesity in RTR and compare to rates in the general Australian population, 2) investigate and compare modifiable lifestyle factors and adipokine levels in RTR with AGT and normal glucose tolerance (NGT) and 3) investigate the effect of a multidisciplinary lifestyle intervention (including dietetic advice) on modifiable CVD risk factors in RTR with AGT. Methods: Chapter 1 presents a review of the literature describing the main nutritional challenges in RTR, cardiovascular risk factors in RTR including adipokine profiles and the role of body composition, diet and PA in RTR. Chapter 2 details the clinical, biochemical, nutritional, body composition, PA and statistical methodologies used in this thesis. In Chapter 3 a descriptive analysis of the anthropometry and cardiovascular risk profile of RTR in an Australian setting is investigated. Chapter 4 investigates the nutritional status of RTR with NGT and AGT in more detail, assessing diet, PA, adipokines and body composition. In Chapter 5, the current literature on lifestyle intervention management (including nutritional management) for obesity and type 2 diabetes mellitus in the general population is discussed. Building on previous chapters, Chapter 6 investigates the effect of a multi-disciplinary lifestyle intervention (with dietetic input) on modifiable cardiovascular risk factors in RTR with AGT. Results: In Chapter 3 it was found that RTR are significantly more centrally obese than those in the general population, and this was particularly the case in younger RTR. Central obesity was associated with CVD risk factors in RTR. Chapter 4 found that a lower level of PA, obesity and central obesity are associated with AGT in RTR, whereas no difference in adipokines or dietary intake was found. In Chapter 6, multidisciplinary lifestyle intervention with dietetic input was found to improve certain risk factors for CVD in RTR with AGT, such as dietary factors (total fat and saturated fat intake) and lipid levels. Conclusions: Central obesity is a common problem in RTR, particularly in those with AGT. Higher levels of PA are associated with lower risk of AGT in RTR, and may help reduce the incidence of central obesity in RTR. Multidisciplinary lifestyle intervention, with dietetic input, can improve some modifiable CVD risk factors in RTR with AGT, however more intensive intervention is required to significantly reduce the incidence of obesity. Key Words: Renal Transplant; Abnormal Glucose Tolerance, Obesity; Cardiovascular Disease; Physical Activity Australian and New Zealand Standard Research Classifications (ANZSRC) 1111 Nutrition and Dietetics, 1102 Cardiovascular medicine and Haematology, 1199 Other Medicine and Health Sciences

Homocysteine, an independent risk factor for cardiovascular disease, is methylated in the liver via the zinc metalloenzyme betaine-homocysteine methyltransferase (BHMT). Established assays for BHMT include a radiochemical assay, a colorometric assay, an HPLC assay and an in vivo microbiological assay. These techniques are either unsuitable for substrate specificity studies, or are unable to give kinetic measurements. BHMT was purified from liver and measured directly and kinetically by a novel ¹H-NMR spectroscopic assay. The disappearance of substrates and the formation of products are monitored simultaneously. Using 2 mM glycine betaine and homocysteine as substrates in 20 mM phosphate buffer (pH = 7.5) and measuring the production of N,N-dimethylglycine the CV is 6.3% (n = 6) and the detection limit is 6 nkatal. An endpoint assay for BHMT activity was also developed and had CV = 5.3%, n = 6, with a detection limit of 2 nkatal. The NMR spectroscopic assay was used to determine the substrate specificity with a library of alternative substrates. Analysis of betaine analogues with different chain length, α-substitution, substitution of the nitrogen and carboxyl moieties demonstrated that BHMT is inactive if there is any steric crowding of the nitrogen or α-carbon positions. BHMT is capable of using group VI heteroatom betaines as methyl donors, with much faster rates than glycine betaine. For glycine betaine the Km was 0.19 ± 0.03 mM with a Vmax of 17 ± 0.7 nMol min-1 mg-1. The same assay was used to detect and partially characterise a BHMT activity from hagfish liver that is similar to that of the mammalian enzyme. NMR spectroscopy was adapted for measurements of glycine betaine in urine, along with other medically significant methylamines. These were shown to be valid for clinical use and in animal studies. A novel metabolite of the sulfonium analogue of glycine betaine (methylsulfinylmethanoate) was identified in rats.

Cardiovascular disease is the leading cause of premature death in the United States today, and vulnerable populations may be more susceptible to this disease risk. Relocating into a new neighborhood may affect one’s cardiovascular disease risk. Through a socio-ecological framework, this study sought to determine whether changes in one’s interior and exterior built environment had a significant effect on cardiovascular disease risk in Atlanta’s relocated public housing population. Using pre- and post-relocation data from a questionnaire delivered to public housing residents, and built environment assessments from before and after demolition neighborhoods, the results showed residents were significantly more satisfied with their new neighborhoods and residences. However, while the interior built environment improved significantly after relocation, the exterior built environment declined significantly. Further, neither overall health nor cardiovascular disease risk improved significantly after relocation. These results corroborate findings in other public housing research that shows that many former public housing residents do not perceive an improvement in their health after relocation.

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