OAR@UM Collection:

Adiposity, lipids and risk for myocardial infarction in the Maltese population

Wed, 01 Jan 2020 00:00:00 GMT

Title: Adiposity, lipids and risk for myocardial infarction in the Maltese population Abstract: Background Myocardial infarction (MI) is a complex disease influenced by both genetic and environmental factors. Aim The Maltese Acute Myocardial Infarction (MAMI) Study is a case-control study that was set up to identify genetic and environmental factors relevant to MI in the Maltese population. Hyperlipidaemia and adiposity as risk factors for myocardial infarction in the Maltese population will be focused on. Furthermore, this study will investigate and apply alternative approaches using high throughput sequencing, extreme phenotypes and biological pathway approaches to determine their use in acquiring more knowledge on the genetic factors of MI. Methods The study includes 423 cases with a first MI between 2011 and 2013, 465 controls that were sex and age-matched in ten year age groups to the cases and 210 relatives of cases. Data on all participants was collected after written informed consent through an extensive interviewer-led questionnaire, measurements and testing and through medical history and records. Results This case-control study identified several important genetic and environmental factors particularly pertinent to the Maltese population. The association of adiposity with risk of MI varied significantly depending on how adiposity was classified, with BMI, the most widely used clinical measure of adiposity, underestimating risk. Waist-hip ratio was more strongly associated with risk of myocardial infarction. Similarly, total cholesterol to high density vii cholesterol ratio and the Non high density cholesterol levels were more strongly associated with risk of MI than the most commonly used clinical measures of dyslipidaemia. The study also gives important insights into how dietary habits in a central Mediterranean climate are influencing the risk of MI with consumption of soft drinks (even diet soft drinks) and bread being strong risk factors whilst nuts, legumes, fruit and red vegetables being protective. The modulation of risk by combinations of different environmental risk factors is exemplified in an analysis performed on smoking and alcohol. The risk associated with APOE and PTPN1 were minimal in the Maltese population. Using an extreme phenotype approach and high throughput sequencing a novel frameshift variant in LDLR likely to cause familial hypercholesterolaemia was identified and polymorphisms in APOB that increase the risk of MI in the Maltese population are described. Conclusions Using the extreme phenotype approach and high throughput sequencing, pathways related to the control of adipogenesis were examined and the findings presented highlight the importance of studying combinations of polymorphisms and using a systems biology approach to analyse the risk of MI in complex pathways. Description: PH.D.

The effect of mind-linked gene disruption in GLIA

Wed, 01 Jan 2020 00:00:00 GMT

Title: The effect of mind-linked gene disruption in GLIA Abstract: Amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) are the most common motor neuron diseases (MNDs) in adults and infants respectively. Both ALS and SMA are characterised by motor neuron loss, muscle atrophy, loss of movement and respiratory insufficiency, which most commonly leads to mortality. Multiple genes are involved in ALS pathogenesis including C9orf72, TARDBP/TDP-43, and FUS. Pathogenic mechanisms involve both loss and gain of function including aberrant messenger RNA (mRNA) processing and trafficking, and production of cytoplasmic inclusions including C9orf72-associated dipeptide repeat aggregates. SMA pathology revolves around the SMN gene where its deletion leads to a decreased SMN protein concentration. SMN together with Gemins 2-8, Unrip, pICln and Tgs1 are required to produce small nuclear ribonucleoproteins (snRNPs), essential for mRNA splicing. Glial involvement in MND has been a subject of current research. The main glial cells are astrocytes, oligodendrocytes, and microglia, fundamental for motor neuron health and maintenance. Using Drosophila melanogaster as a model organism and the bipartite GAL4- UAS system, various ALS- and SMA-linked genes were disrupted selectively in glia and flies were assessed for motoric ability and survival. Disruption of the ALS-linked TDP-43, FUS, C9orf72 and SCFD1 led to significant decreases in larval mobility with the large majority of all transgenes applied inducing complete loss of adult fly viability. Disruption of the SMA-linked SMN, pICln, Tgs1 and Gemin3 did not affect larval mobility with the exception of Gemin8/Valette. Nonetheless, viability was negatively affected on disruption of nearly all SMA-linked genes. These results show a very important glial contribution to the normal pathogenesis of MND and uncover novel contributors to the function and survival of glia. This can be exploited for future therapeutic strategies possibly enhancing their effectiveness. Description: B.SC.(HONS)APPLIED BIOMED.SCI.

Glycaemic control and its relation to foot skin pH in people living with type 2 diabetes mellitus

Wed, 01 Jan 2020 00:00:00 GMT

Title: Glycaemic control and its relation to foot skin pH in people living with type 2 diabetes mellitus Abstract: Aim: To determine any differences in foot skin pH values in people living with type 2 diabetes presenting with different glycaemic control levels within the Maltese population, when compared to healthy individuals. Research Design and Method: A quantitative comparative observational study was conducted on a population of Maltese patients living with type 2 diabetes and a group of healthy patients, as controls. Two hundred and forty-one participants (n=241) were recruited for this study, 180 living with type 2 diabetes mellitus and 61 healthy participants. The participants living with type 2 diabetes were categorised into 3 different groups according to their HbA1c levels. A 20 minutes acclimatisation period was given to each participant before skin pH testing commenced. Demographic information such as age, gender, weight, height, diabetes duration, medications, BMI, daily physical activity and alcohol intake were recorded prior to testing. Once the acclimatisation period was over, skin pH at predefined sites (plantar, interdigital and dorsal areas of each foot) was measured utilizing the Skin pH meter (Apera PH60F). Participants required to attend for only a single session. The researcher followed a predefined protocol when taking skin pH readings for each participant. The Shapiro-Wilk test was used to determine the normality of data. The Kruskal Wallis test was employed to determine if a significant difference was found between groups, while other statistical tests such as the Shapiro-Wilk, Spearman correlation, Mann Whitney and Chi-square tests were used to analyse and compare other variables in relation to foot skin pH. Results: The study found a significant difference (p < 0.05) between mean skin pH at the 3 regions of interest (ROI) and the 4 groups of participants recruited in the study. Group 2 (good HbA1c) presented with the lowest foot skin pH in all ROI, followed by group 1 (healthy), group 3 (fair HbA1c) and with group 4 (poor HbA1c) having the highest skin pH values. The mean interdigital foot skin pH was always higher (less acidic in nature), when compared to the other sites for both the left and right foot across all groups. The higher the HbA1c score, the higher (less acidic) the mean foot skin pH was observed in all ROI. Conclusions: The results of this study demonstrated significant differences between the four groups and concluded that the more controlled blood glucose levels, the less foot skin pH tends to fluctuate from the normal acidic values. With the aid of this study health policies should start considering testing for skin pH especially in the foot region to enable health professionals to pinpoint disturbances in the skin acid mantle which can result in frequent skin infections and conditions affecting immunocompromised patients such as those with uncontrolled diabetes. Description: M.Sc. (Melit.)

Generating a bacterial clone for evaluating growth under stress

Wed, 01 Jan 2020 00:00:00 GMT

Title: Generating a bacterial clone for evaluating growth under stress Abstract: Climate change is a major global concern, with implications regarding (amongst others) changes in the universal microbial proliferation due to alterations of the environmental conditions. Subsequent bacterial adaptation to climate variation (i.e. acclimatisation) can result in an effect, as of yet unknown, with regards to their ability to grow and propagate. The project aimed to create an Isopropyl β- d-1-thiogalactopyranoside-inducible enhanced Green Fluorescent Protein (eGFP) synthesising reporter Escherichia coli clone via chemical transformation, which would then be used as part of an eGFP/Propidium iodide (PI) cell viability assay. Information obtained from this model organism should be applicable to other Gram-negative organisms and allow for a complete understanding of the mechanisms of bacterial response to environmental stress. The study generated E. coli BL21 (DE3) pD454- MBPeGFP, validated and characterised it. A 150 nM PI concentration to be optimal for the eGFP/PI assay, however the use of PI was determined to be inappropriate to kinetic assays. Growth was assessed using three parameters: lag (λ), maximum growth rate (µmax), and fluorescent time to detection values (FTTD). λ decreased with increased carbon dioxide (CO2), and temperature. Values for µmax were not affected by increases in CO2 but diminished with increased temperatures. FTTD values demonstrated its application to assessing changes at lower levels of inoculum; application may vary according to a study’s objectives. Future work should aim for characterising responses to changes in other variables such as pH. Description: B.SC.(HONS)BIOMED.SCI.