/library/oar/handle/123456789/118844 2026-06-14T15:59:22Z /library/oar/handle/123456789/146315 Title: MRI perfusion of solitary parotid lesions : a prospective study Abstract: Background: Parotid tumours (PTs) have a variety of pathological subtypes, each requiring distinct surgical approaches. Nevertheless, the current preoperative diagnostic methods often fall short in providing accurate PT diagnoses. Aim: Can DCE-MRI help predict histology in patients with focal parotid lesions? Design: A prospective study recruiting patients with known focal lesions of the parotid gland who are being worked up for surgery. A dynamic contrast-enhanced MRI (DCE-MRI) scan is performed, after which post-processing of data is used to obtain MR perfusion quantitative parameters (Ktrans, Kep and Ve) obtained by drawing a region of interest (ROI) over the PT. In this study 2 individual sets ROIs were drawn by two authors. The first set of ROIs vary in size, whereas the second are a fixed range ROI size limited to 10-20mm². The information obtained from DCE-MRI is compared to tissue histology and cytology, to assess the diagnostic accuracy of the DCE-MRI. The intra and inter-observer correlation of the different ROI methods is also assessed. Ethical standards were adhered to, with informed consent obtained from all participants. The data collection and analysis process spanned approximately 10 months. Methods: In this prospective study, 15 patients with histologically or cytologically proven PTs who underwent DCE-MRI were enrolled including 7 pleomorphic adenomas (PAs) and 8 Warthin’s tumours (WTs). Quantitative parameters of DCE-MRI (Ktrans, Kep, and Ve) of lesions were calculated and analysed. A second set of analysis was done to assess the intra and inter-observer correlation when using different ROI techniques. Results: Statistically significant (p < 0.05) inter-group differences were found between PA and WT for Kep and Ve. Correlation with histological results using the Mann-Whitney U test, where Ktrans, Kep and Ve were found to have p-values of 0.132, 0.008 and 0.003 respectively. Inter-observer correlation for the first set of variable size ROIs for the different MRI parameters were: Ktrans 0.590, Kep 0.622 and Ve 0.848, and for the second fixed range set Ktrans 0.945, Kep 0.901 and Ve 0.964. The intra-observer results for author 1 for the different MRI parameters were: Ktrans 0.358, Kep 0.718 and Ve 0.436. The intra-observer results for author 2: Ktrans 0.950, Kep 0.581 and Ve 0.762. Conclusions: In summary, DCE-MRI perfusion parameters aid in the differentiation of PA and WT. This technique demonstrates reliability and reproducibility. Standardised ROI sizes with fixed ranges minimise the impact of radiologist experience on perfusion parameter calculations, resulting in better interobserver agreement. However, when evaluating the reproducibility of perfusion parameters obtained by the same reader using different ROI techniques, radiologist experience significantly affects parameter calculations. Description: M.Sc.(Melit.) 2024-01-01T00:00:00Z /library/oar/handle/123456789/145652 Title: Barriers and facilitators to physical activity in overweight adults in Malta : a qualitative analysis Abstract: Overweight and obesity are significant public health concerns in Malta, reflecting a worldwide pattern of increasing prevalence across various demographics. Previous studies have established a positive link between physical activity and weight management. Research investigating the barriers and facilitators affecting physical activity participation among overweight and obese adults in the local context is still lacking. The main purpose of this study is to explore these factors hence addressing the research gap. Utilising a qualitative research approach, the study delved into the lived experiences of individuals carrying excess weight. Participant interviews revealed a spectrum of barriers and facilitators, uncovering the complex interaction of intrinsic, environmental, and social factors influencing engagement in physical activity. The study identified carrying excessive weight and poor infrastructure as major barriers, while a desire for better health and exercising with companions emerged as key facilitators. Findings from this study lay a foundation for the development of targeted policies and strategies designed to foster an environment that facilitates and promotes active lifestyles. The study also contributed to the generation of new theories, potentially stimulating future research. Description: M.Sc.(Melit.) 2024-01-01T00:00:00Z /library/oar/handle/123456789/141609 Title: Development of an innate immune cell tolerance model Abstract: Sepsis has been defined as the ‘life-threatening organ dysfunction caused by a dysregulated host response to infection’ carrying a poor prognosis and high mortality rates, both during its progression, as well as after hospital discharge, rendering it quite the adversary to modern medicine. One contributory aspect to this high mortality rates is sepsis-induced immune suppression, where cells of the innate immune system enter a state of tolerance and functional reprogramming, dampening any subsequent immune reaction to secondary infections. The work done in this dissertation aimed to develop an in vitro model of immune tolerance that serves as a standard on which future experimentation may be carried out. This was done by isolating and purifying human primary monocytes from young blood donors, characterising them using CD14, HLA-DR and FACS flowcytometry. Subsequently, a re-stimulation protocol was applied using bacterial LPS in order to induce endotoxin tolerance. The success in generating the tolerant state was assessed following the generation of significant differences in the mean cytokine secretion levels of TNF-α, IL-1β and IL-10 using ELISA and statistical computation, as well as through the confirmation of a retention in overall cell viability throughout using 7-AAD. It was found that a tolerant state was induced within the monocytes and macrophages, with TNF-α producing the most significant difference in mean secretion concentrations between the first and second stimulation, generating a pvalue of 7.824x10-4 . The differences in IL-1β and IL-10 secretion levels were 0.000542794 and 0.018214324, respectively. Following 7-AAD analysis, the overall cell viability was retained, indicating the successful acquisition of a tolerant state within the CD14+ , HLADR+ cell population. Description: B.Sc. (Hons) Med. Biocem.(Melit.) 2024-01-01T00:00:00Z /library/oar/handle/123456789/141359 Title: Unravelling the mechanisms of xanthine oxidoreductase chain formation : insights into protein structure and function Abstract: Xanthine oxidoreductase (XOR) catalyses the last two steps of purine catabolism, converting hypoxanthine to xanthine and subsequently to uric acid. From these reactions, hydrogen peroxide and superoxide anion radicals can be generated. Increased activity of XOR may result in hyperuricemia due to higher production of uric acid and oxidative stress from increased generation of reactive oxygen species (ROS). Hyperuricemia is associated with cardiovascular diseases, including stroke, and hypertension. Hypertension is linked to the depletion of nitric oxide by ROS and the subsequent production of peroxynitrite radicals. Various mutations have also been associated with high XOR activity as well as a higher risk of different conditions, such as hypertension, hyperuricemia, and xanthinuria. From previous studies, it was also shown that XOR can form filaments that may have a role in its enzymatic activity. In this project, the hXOR wildtype (WT) and one clinical mutation identified in a Maltese study, I646V, were characterised. The aim of the project was to determine of wild type hXOR and the I646V assembled into filaments formation and whether the filaments are enzymatically active. Transformed TP1000 E. coli cells harbouring either the pTrcHis-hXOR WT or I646V variant were grown under aerobic and anaerobic conditions in order to compare the filament formation and enzymatic activity. This approach aimed to elucidate the enzymatic role in physiological ischaemic conditions. Some samples were also subjected to heat shock to enhance the folding and activity of hXOR. Purification was carried out using immobilized metal affinity chromatography, with purity and yield assessed by SDS-PAGE. Filament presence was confirmed via Native-PAGE. Additionally, hXOR activity was evaluated using the uric acid spectrophotometric assay and the Nitro Blue Tetrazolium (NBT) assay. The secondary structure and melting temperature were analysed using circular dichroism. Production of XOR under anaerobic conditions resulted in a higher enzymatic activity for both the WT and I646V variant. For the samples produced under aerobic conditions, the I646V variant had the highest activity but had the lowest yield and stability. On the other hand, hXOR WT grown under anaerobic conditions was the most active out of all conditions tested and had the highest stability. Filament formation was observed in most conditions, with anaerobic growth conditions seemingly favouring filament formation for both WT and mutant. Moreover, the filaments formed retained activity as shown in the NBT assays. These findings are particularly important as filament formation might modulate the enzymatic activity of hXOR. Additionally, the observed increase in hXOR activity under anaerobic conditions is noteworthy, as physiologically, hXOR can be produced under hypoxic and ischemic conditions. The high activity of hXOR produced in such environments may result in significant ROS production, potentially leading to various adverse health conditions. Description: B.Sc. (Hons) Med. Biocem.(Melit.) 2024-01-01T00:00:00Z