/library/oar/handle/123456789/61743 2025-11-03T11:12:05Z /library/oar/handle/123456789/119858 Title: Functional characterisation and pharmacogenetic relevance of a novel gene associated with poor lung function Abstract: Introduction: The single nucleotide polymorphism (SNP) rs6889822 has been reported to be sentinel SNP in a leading genome wide association study (GWAS) which strongly associated the HTR4 gene with the phenotype for altered lung function and COPD. It has also been identified as an expression quantitative trait locus (eQTL) of FBXO38 gene expression in humans and although to date literature supports no direct role for the FBXO38 gene in lung diseases, the eQTL association between rs6889822 and FBXO38 provides a basis for this. Aim: To study the influence of experimentally altered knockdown and overexpression of the FBXO38 gene on downstream pathways, using an in vitro airway cell culture model. Methodology: Knockdown of the FBXO38 gene in H460 airway lung model and HEK-293 experimental model was carried out through transfection of FBXO38 specific siRNA duplexes. An overexpression plasmid vector for delivery of wild type FBXO38 into the H460 lung model and HEK-293 experimental model was designed. Delivery of both the siRNA and recombinant FBXO38 plasmid was carried out by magnetofection. A comparative transcriptome carried out on duplicate samples between normal and altered FBXO38 overexpression and knockdown was obtained through RNA sequencing. The resulting sequencing data was bioinformatically analysed using a differential expressed genes (DEG) and gene set enrichment analysis (GSEA) approaches for patterns of differential gene expression and pathways associated with poor lung function. Results: Following analysis of RNAseq knockdown and overexpression data, 11 significantly differentially expressed genes were isolated through DEG analysis, and 3 significantly activated pathways were identified using GSEA analysis. A combination of bioinformatics and literature review particularly identified three differentially expressed genes, JUN, MAP2 and ITCH to have important airway regulatory roles tied to FBXO38 knockdown. The ubiquitination and proteasome degradation pathway was identified as being significantly activated with respect to FBXO38 knockdown. No differential expression was observed in overexpression samples. Conclusion: The results propose a role for FBXO38 in deregulation of the airway proteasome through its action as an E3 ubiquitin ligase capable of exerting an SCF dependant regulatory effect characteristic of its F-box protein class. In addition to this the genes JUN, MAP2 and ITCH were identified to have important airway regulatory roles tied to FBXO38 knockdown. The combined strengths of these observations propose FBXO38 to be a strong and promising potential candidate for further study in relation to altered lung function and the pathophysiology of chronic airway disease. Description: M.Phil.(Melit.) 2020-01-01T00:00:00Z /library/oar/handle/123456789/119693 Title: The knowledge of the Maltese population on the prevention and control of mosquito borne diseases Abstract: Background: Mosquito-borne diseases (MBDs) are a re-emerging threat that merits attention. This has been highlighted by autochthonous transmission of dengue and chikungunya in various European countries. Any effective strategy to mitigate the threat locally will require public engagement. This study will generate data on the prevailing knowledge, attitudes and practices of the Maltese population when it comes to mosquito control as well as the knowledge and preparedness of local doctors in the eventuality of diagnosing an MBD. This research has been carried out with the purpose of identifying any knowledge gaps and corresponding socio-economic predictors. Methods: The research involves a general public survey comprising 394 Maltese respondents aged sixteen and above. It is a cross-sectional survey carried out in the form of telephone interviews. A second survey was emailed to local GPs and family medicine practitioners, gathering a total of 137 responses. Results Few respondents (7.1%) knew of MBDs other than malaria. Only 55% of respondents knew that mosquitoes required water to lay eggs, 64.2% could correctly identify suitable breeding sites. A majority of 67.1% of respondents reported being minimally worried about MBDs. Only 25.3% of respondents emptied their saucers every three to seven days. The majority (78.7%) of respondents think that the responsibility lies with both environmental authorities and the public. 81.2% of respondents indicated a willingness to be further educated on MBDs and available precautions. The interviewed GPs have a higher knowledge of MBDs compared to the rest of the population, with malaria (39%) and zika (24.3%) most likely to be identified as significant public health threats by them. Results: obtained from the other questions show that the interviewed GPs are inadequately trained to recognise MBD symptoms and take the necessary steps in the eventuality of coming across an MBD case. Only 58.8% of interviewed GPs responded that they would notify public health authorities on suspecting an MBD case and even fewer (44.9%) would have taken lab samples. The interviewed GPs’ ability to match MBDs with case study symptoms was also found to be low when it came to MBDs such as West Nile (36%), chikungunya (54.4%) and dengue (50%). The higher matching rate of malaria (79.4%) and Zika (85.3%), with their respective case symptoms, may be due to give-aways in the descriptions, such as the mentioning of parasites and microcephaly. Conclusion: This is the first study of its kind in Malta, demonstrating that the Maltese population is unfamiliar with the risks posed by MBDs and that the interviewed GPs are inadequately trained to recognise MBD symptoms and proceed accordingly. There are significant knowledge gaps in mosquito-related information, especially among younger respondents. This study recommends raising awareness and preparedness by improved training of GPs as well as other stakeholders who can pass on subject-related information such as teachers, pharmacists and garden centre employees. Alternative media sources such as social media should also be considered to raise awareness among the younger and more educated socio demographics. Description: M.SC.PUBLIC HEALTH 2020-01-01T00:00:00Z /library/oar/handle/123456789/118277 Title: Pregnant women’s attitudes, awareness and knowledge about perinatal depression Abstract: Background: Perinatal depression (PD) is an important public health problem that is associated with high maternal morbidity and mortality, and negative long-term consequences for children and families. Globally, around 12% of women are affected, either during pregnancy or in the first year after childbirth. In Malta, the condition is also common with point prevalence rates of around 15% and 9% for antenatal and postnatal depression respectively. Research on PD and more specifically on attitudes, awareness and knowledge about PD is scarce, especially within the local context. Literature suggeststhat these three variables may be influenced by various socio-demographic and clinical variables, ultimately impacting on women’s help-seeking intentions. This study follows the recently launched Maltese Mental Health Strategy which also hints at the local perinatal mental health scenario. It aims to explore the attitudes, awareness and knowledge of PD among pregnant Maltese women seeking routine antenatal care at Mater Dei Hospital. Methodology: A cross-sectional paper-based quantitative survey was conducted between April and July 2019. The study utilised an already established research tool, the Perinatal Depression Monitor, which was adapted to the local population and then subjected to psychometric testing. A convenience sample of 404 pregnant women were recruited for the study with the booking midwives acting as intermediaries in the distribution of the questionnaire. The data collected was analysed using statistical software. Descriptive data was generated and univariate and multivariate regression analyses were conducted. Results: The study participants generally held positive attitudes towards PD and screening measures that identify this condition. A multivariate linear regression model indicated that the main predictors of such attitudes were parity (p-value: 0.006), gestational age (p-value: 0.017), level of education (p-value:<0.001), and marital status (p-value: 0.018). Awareness of PD among the sample appeared high. 79.8% of participants were able to recognise the term PD, yet there seemed to be a marked difference in the unprompted awareness of antenatal and postnatal depression. Conversely, prompted awareness of PD was high, although some groups of participants presented higher awareness of postnatal PD than others. Despite being aware, most participants were unable to correctly define PD or estimate its prevalence rate, suggesting some important gaps in the participants’ level of knowledge. Non-pharmacological treatment options were the most frequently cited treatment option, with most participants claiming they would choose help from a doctor, especially those who had training in health (p-value: 0.021) or mental health (p-value: 0.0017). However, if personally affected by the condition, the majority claimed they would resort for help from family and friends, except for those with lower levels of education (p-value: 0.005) and those not gainfully employed (p-value: 0.007) who claimed they would seek no help at all. Conclusion: Notwithstanding its limitations, this research provides an important snapshot of Maltese pregnant women’s attitudes, awareness and knowledge about PD. The study findings are particularly valuable to policy makers in the development of targeted education and awareness campaigns, in the drawing up of pathways for community and mental health practices, and in future maternal health services planning. Description: M.Sc.(Melit.) 2020-01-01T00:00:00Z /library/oar/handle/123456789/118276 Title: Foot care knowledge and practices amongst Maltese individuals with diabetes : trends and determinants Abstract: Diabetes Mellitus (DM) is one of the emergent global health emergencies of the 21st century. In 2019, The International Diabetes Federation estimated that 463 million people had DM and this number was predicted to reach 578 million by 2030, and 700 million by 2045. Between 2014 and 2016, the prevalence of individuals with Type 2 DM aged between 25 to 64 years in Malta was found to be 10.39% (95% CI: 9.47-11.38) (Cuschieri, Vassallo, Calleja, Pace, & Mamo, 2016). DM not only lessens the quality of life and life expectancy but also leads to several microvascular and macrovascular complications, including those affecting with the lower limb (LL). The burden of DM-associated complications worldwide is a chief healthcare problem. Patient self-management is crucial to effectively manage DM and prevent its complications, including those of the LL. Some of the risk factors can be minimised if individuals have satisfactory knowledge of foot-care and are able and motivated to transfer that knowledge into practice (Chiwanga & Njelekela, 2015). International studies have shown inequalities in foot-care knowledge and practices across the globe. Various potential determinants have been identified, with cultural issues being amongst those factors found to possible influence foot care. Although small scale studies on foot-care were conducted in Malta, these failed to effectively address determinants of foot-care knowledge and practice. Hence, this study was aimed to investigate the trends and determinants of foot-care knowledge and practice amongst individuals with Type 2 DM living in Malta. Description: M.Sc.(Melit.) 2020-01-01T00:00:00Z