Health of the older worker in Ireland - occupational physical and psychosocial factors in the autumn of work life

Introduction: Worldwide, governments are striving to keep people in work to an older age. However, little is known about the effects of work on an older workforce. This thesis aims to investigate the importance of job characteristics to the antecedents and evolution of cardiovascular disease and functional limitations for the older worker (50+ years). Methods: Three studies were used in this thesis. The 5C (Cork Coronary Care Case- Control) Study investigated the association between job strain and a coronary event in males (n=208) 35-74 years old. The Mitchelstown Study examined the association between job characteristics and positive lifestyle behaviours and further, job characteristics and blood pressure for males and females 50-69 years (n=2,047). Finally, the Cork & Kerry Study investigated the physical effects of manual work and reported functional limitations/disabilities in a sample of 60-80 year olds (n=362). Results: Results from the 5C Study show a clear difference between younger (<50 years) and older (≥50 years) workers, with older workers who had a coronary event more likely to have high job strain and low job control. Data from the Mitchelstown Study showed workers with intermediate possibility for development or high quantitative demands (versus low) at work significantly more likely to have co-occurrence of positive lifestyle behaviours. Further, those who had high possibility for development were more likely to have high systolic blood pressure with no indication of recovery from this activation at night. Physically demanding work as reported by the participants of the Cork & Kerry Study was associated with functional limitations and activities of daily living disability for both the paid and unpaid worker. Discussion: The findings from this piece of work highlight the necessity to examine job characteristics and health outcomes in isolation for the over fifties. The challenge is to get this information into the workplace.

Defining metabolically healthy obesity: role of dietary and lifestyle factors

Background: There is a current lack of consensus on defining metabolically healthy obesity (MHO). Limited data on dietary and lifestyle factors and MHO exist. The aim of this study is to compare the prevalence, dietary factors and lifestyle behaviours of metabolically healthy and unhealthy obese and non-obese subjects according to different metabolic health criteria. Method: Cross-sectional sample of 1,008 men and 1,039 women aged 45-74 years participated in the study. Participants were classified as obese (BMI ≥30kg/m2) and non-obese (BMI <30kg/m2). Metabolic health status was defined using five existing MH definitions based on a range of cardiometabolic abnormalities. Dietary composition and quality, food pyramid servings, physical activity, alcohol and smoking behaviours were examined. Results: The prevalence of MHO varied considerably between definitions (2.2% to 11.9%), was higher among females and generally increased with age. Agreement between MHO classifications was poor. Among the obese, prevalence of MH was 6.8% to 36.6%. Among the non-obese, prevalence of metabolically unhealthy subjects was 21.8% to 87%. Calorie intake, dietary macronutrient composition, physical activity, alcohol and smoking behaviours were similar between the metabolically healthy and unhealthy regardless of BMI. Greater compliance with food pyramid recommendations and higher dietary quality were positively associated with metabolic health in obese (OR 1.45-1.53 unadjusted model) and non-obese subjects (OR 1.37-1.39 unadjusted model), respectively. Physical activity was associated with MHO defined by insulin resistance (OR 1.87, 95% CI 1.19-2.92, p = 0.006).

Formation and electrical interfacing of nanocrystal-molecule nanostructures

The objective of this thesis work is to develop methods for forming and interfacing nanocrystal-molecule nanostructures in order to explore their electrical transport properties in various controlled environments. This work demonstrates the potential of nanocrystal assemblies for laterally contacting molecules for electronic transport measurements. We first propose a phenomenological model based on rate equations for the formation of hybrid nanocrystal-molecule (respectively: 20 nm – 1.2 nm) nanostructures in solution. We then concentrate on nanocrystals (~ 60 nm) assembled between nano-gaps (~ 40 nm) as a contacting strategy for the measurement of electronic transport properties of thiophene-terminated conjugated molecules (1.5 nm long) in a two-terminal configuration, under vacuum conditions. Similar devices were also probed with a three-terminal configuration using thiophene-terminated oxidation-reduction active molecules (1.8 nm long) in liquid medium for the demonstration of the electrolytic gating technique. The experimental and modelling work presented in this thesis project brings into light physical and chemical processes taking place at the extremely narrow (~1 nm separation) and curved interface between two nanocrystals or one nanocrystal and a grain of a metallic electrode. The formation of molecular bridges at this kind of interface necessitates molecules to diffuse from a large liquid reservoir into the region in the first place. Molecular bonding must occur to the surface for both molecular ends: this is a low yield statistical process in itself as it depends on orientation of surfaces, on steric hindrance at the surface and on binding energies. On the other hand, the experimental work also touched the importance of the competition between potentially immiscible liquids in systems such that (organo-)metallic molecules solvated by organic solvent in water and organic solvent in contact with hydrated citrate stabilised nanocrystals dispersed in solutions or assembled between electrodes from both experimental and simulations point of view.

Immune and stress factors in the pathophysiology of the mdx mouse model of Duchenne Muscular Dystrophy

Duchenne Muscular Dystrophy (DMD) is a fatal multi-system neuromuscular disease caused by loss of dystrophin. The loss of dystrophin from membranes of contractile muscle cells and the dysregulation of the DAPC, induces chronic inflammation due to tissue necrosis and eventual replacement with collagen which weakens muscular force and strength. Dystrophin deficiency may cause under-diagnosed features of DMD include mood disorders such as depression and anxiety and dysfunction of the gastrointestinal tract. The first study in the thesis examined mood in the dystrophin-deficient mdx mouse model of DMD and examined the effects of the tri-cyclic antidepressant, amitriptyline on behaviours. Amitriptyline had anti-depressant and anxiolytic effects in the mdx mice possibly through effects on stress factors such as corticotrophin-releasing factor (CRF). This antidepressant also reduced skeletal muscle inflammation and caused a reduction in circulating interleukin (IL)-6 levels. In the second and third studies, we specifically blocked IL-6 signalling and used Urocortin 2, CRFR2 agonist to investigate their potential as therapeutic targets in mdx mice pathophysiology. Isometric and isotonic contractile properties of the diaphragm, were compared in mdx mice treated with anti IL-6 receptor antibodies (anti IL-6R) and/or Urocortin 2. Deficits in force production, work and power detected in mdx mice were improved with treatment. In study three I investigated contractile properties in gastrointestinal smooth muscle. As compared to wild type mice, mdx mice had slower faecal transit times, shorter colons with thickened muscle layers and increased contractile activity in response to recombinant IL-6. Blocking IL-6 signalling resulted in an increase in colon length, normalised faecal output times and a reduction in IL-6-evoked contractile activity. The findings from these studies indicate that for both diaphragm and gastrointestinal function in a dystrophin-deficient model, targeting of IL-6 and CRFR2 signalling has beneficial therapeutic effects.