https://www.um.edu.mt/library/oar/handle/123456789/86300 Sat, 25 Apr 2026 03:02:20 GMT 2026-04-25T03:02:20Z https://www.um.edu.mt/library/oar/handle/123456789/86408 Title: FXIIIB p.H95R and intron K polymorphisms and risk of myocardial infarction in the Maltese Abstract: The clotting cascade is a natural process that is essential in the occurrence of a vascular injury for the prevention of bleeding. This is however not beneficial when unnecessary clot build-up leads to myocardial infarction (MI), stroke or deep vein thrombosis. For instance, variations present in coagulation factor XIII (FXIII) are thought to influence the factor’s activity, which could ultimately affect the risk of MI. The most common variation studied is FXIIIA p.Val34Leu. Locally, studies of FXIIIB-subunit variants: FXIIIB p.H95R and FXIIIB intron K polymorphism have not yet been carried out. Thus, in this study, these polymorphisms were investigated in samples of the Maltese population obtained from the Maltese Acute Myocardial Infarction (MAMI) study. Genotyping analysis for this study was carried out with a kompetitive allele specific polymerase chain (KASP) reaction assay for FXIIIB p.H95R and a TaqMan assay for FXIIIB intron K. Allele frequency for the FXIIIB intron K was at 87%% for the reference allele and 13% for the alternative allele whilst for FXIIIB p.H95R these were at 91% and 9% respectively. For the median FXIII activity analysis, it was noted that this was similar in males and females as well as in cases, control and relatives. Furthermore, this showed no correlation with the different metabolic and environmental factors analysed. However, stratification for FXIIIB intron K genotypes showed that individuals possessing the alternative allele had a markedly lower FXIII activity level. For FXIIIB p.H95R, there is no significant difference in median FXIII activity between the genotypes. The FXIIIB intron K has a protective effect on MI (ORHom Alt 0.27; 95% CI 0.08-0.98), while FXIIIB p.H95R shows no change in risk of MI (ORHet 1.07 95%CI 0.71-1.61). The protective effect of the intron K variant was lost in individuals in the highest fibrinogen tertile. On combination of both polymorphisms, individuals who were heterozygous and homozygotes alternative for a single polymorphism potentially showed a slight decrease in risk of MI (OR 0.80; 95% CI 0.55-1.17 and OR 0.79; 95%CI 0.51-1.24), whilst a suggestive slight increase was noted for compound heterozygotes (OR 1.45; 95%CI 0.57-3.72). Description: B.Sc. (Hons)(Melit.) Fri, 01 Jan 2021 00:00:00 GMT https://www.um.edu.mt/library/oar/handle/123456789/86408 2021-01-01T00:00:00Z https://www.um.edu.mt/library/oar/handle/123456789/86406 Title: Isolation and characterisation of imatinib-resistant extracellular vesicles Abstract: Chronic myeloid leukaemia (CML) is a malignant myeloproliferative disorder of the haematopoietic progenitor cells, having an average age of onset of 50-60 years. Imatinib is the first tyrosine kinase inhibitor (TKI) designed as a first-line therapeutic drug for CML, that greatly increases the 5-year relative survival from 20-30% to 50- 90%. However, if given for long periods of time 1/3rd of patients will develop TKI resistance which poses a problem as the patients do not respond optimally and CML will ultimately progress towards the more aggressive pathogenic phenotypes. In previous studies, exosomes from imatinib-resistant (IR) K562 CML cells have been shown to internalize into imatinib-sensitive (IS) K562 CML cells after incubation. This raises the question of whether exosomes from IR cells are able to confer resistance to IS cells. In this study we will compare exosomes from IR cells with exosomes from IS cells via flow cytometry and we will be assessing the viability of cells via MTT assays. In this experiment, both IS and IR cells share two different populations differing in size, likely due to an adaptive phenotypic shift, with IS cells having a larger percentage of the population consisting of smaller cells and IR cells having a higher percentage of the population of larger cells. IR cells show a greater expression of CD63 and CD81 when compared to IS cells, yet both lack expression of CD9. The population consisting mainly of IR cells is CD45 negative, whereas the other population making up IS cells is CD45 positive. Exosomes derived from IR cells have a higher expression of CD63, CD81 and CD9 when compared to exosomes from IS cells. However, CD45 expression was absent on both types of exosomes. From the MTT assays, neither the addition of IR nor IS exosomes mediated IM resistance to IS cells. The observation of phenotypic shift can aid in development of new specifically-targeted treatment options for CML. Description: B.Sc. (Hons)(Melit.) Fri, 01 Jan 2021 00:00:00 GMT https://www.um.edu.mt/library/oar/handle/123456789/86406 2021-01-01T00:00:00Z https://www.um.edu.mt/library/oar/handle/123456789/86403 Title: Investigating the viability of thawed fresh frozen plasma stored between 2°C to 6°C for 24 hours Abstract: Whole Blood (WB) is primarily composed of erythrocytes, leucocytes, platelets and plasma. These constituents have their own morphological features and properties which are necessary for them to carry out their respective function. Fresh Frozen Plasma (FFP) is essentially plasma that has been immediately frozen upon donation and separation from the rest of the other blood constituents. Patients who have endured traumatic episodes such as major bleeding events, are mainly given plasma to be sustained with those factors which are deficient or being depleted. Prior to transfusion, FFP must first be thawed at 37°C in order to be able to be given to the patient. Currently the Maltese guidelines suggest that thawed FFP which is stored between 2°C to 6°C should be transfused within 6 hours after being thawed. This study focuses on determining whether FFP remains viable 24 hours post-thawing in refrigerated conditions by measuring some important factors and parameters such as Factor VIII and Prothrombin Time (PT) before and after the 24-hour period to be able to compare and examine the difference, if any. Results obtained from this study show that most of the coagulation factors which were under investigation can indeed be considered as being suitable for transfusion since their values remained within the normal range and above the minimum acceptable level. On the contrary, the same cannot be said for coagulation Factor VIII since its levels dropped significantly below the normal range and below the minimum acceptable level. The overall quality of thawed FFP stored in the aforementioned conditions is difficult to establish however, it is imperative to consider the patient’s situation before FFP administration could be done. Thawed FFP stored for an entire day in refrigerated conditions could be useful in certain scenarios since particular parameters, such as Factor V, were found to be suitable, safe and effective for treatment purposes. Description: B.Sc. (Hons)(Melit.) Fri, 01 Jan 2021 00:00:00 GMT https://www.um.edu.mt/library/oar/handle/123456789/86403 2021-01-01T00:00:00Z https://www.um.edu.mt/library/oar/handle/123456789/86374 Title: Association of the WNT16 Kozak sequence variant rs55710688 with BMD and fractures in Maltese postmenopausal women Abstract: Osteoporosis is a skeletal disease characterised by a reduction in bone mass and microarchitectural deterioration of bone resulting in an increased fracture risk. The WNT16 protein encoded by the WNT16 gene is a ligand that activates canonical WNT signalling leading to increased bone formation. The WNT16 rs55710688 insertion variant (CCCA), located in the Kozak sequence of exon 1, elevates the translational efficiency of WNT16. The study aimed to determine if the WNT16 rs55710688 variant is associated with spine and hip BMD, and fracture risk at different anatomical sites in the Maltese population. Genotyping was performed in the MOFS case-control collection of 1,045 postmenopausal women using Competitive allele specific PCR. Genotype-phenotype associations were investigated using the Mann-Whitney and Kruskal-Wallis tests, whereas risk ratios were computed using logistic regression models providing odds ratios (ORs) with 95% confidence intervals (CI) adjusted for confounders. Genotyping was successful in 1,034 samples, with the reference and alternative allele frequencies detected at 75.8% and 24.2% respectively, which are in line with European populations. Genotype-phenotype associations showed that homozygosity for the alternative allele was associated with a higher lumbar spine (LS) BMD (p=0.04) and T-score (p=0.04) relative to homozygosity for the reference allele. Heterozygosity was associated with a higher total hip (TH) BMD (p=0.04) and T-score (p=0.04). A trend was also observed for femoral neck (FN) BMD in women with the homozygous alternative genotype having a higher BMD at this site. However, the association did not reach statistical significance (p=0.08). Risk ratios revealed that women with the homozygous alternative genotype exhibited a protective effect on LS BMD (age-adjusted OR: 0.4[95% CI 0.2-0.9], p=0.02) compared to women with the homozygous reference genotype. Additionally, homozygosity for the reference allele was associated with decreased risk of all-type of low-trauma fractures (age- & BMD- adjusted OR: 0.5[0.2-0.9], p=0.02). A weak association was observed with wrist fracture risk (age- & BMDadjusted OR: 0.4 [95% CI 0.1-1.1], p=0.07) possibly due to the low sample size. In conclusion, results indicate that the WNT16 rs55710688 variant exerts a protective effect on vertebral and hip BMD, highlighting its effect on trabecular and cortical bone. The results support the functional findings showcasing the increased transcriptional efficiency of WNT16 in the presence of the WNT16 rs55710688 alternative allele. Thus, the variant is a possible genetic variant underlying the complex genetics of osteoporosis and fracture risk in Malta. Description: B.Sc. (Hons)(Melit.) Fri, 01 Jan 2021 00:00:00 GMT https://www.um.edu.mt/library/oar/handle/123456789/86374 2021-01-01T00:00:00Z