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- ThesisRestrictedINSOMNIA AND SLEEP HYGIENE AMONG ADULTS IN AN URBAN COMMUNITY IN KEPONG, MALAYSIA.(International Medical University, 2024)Introduction: Insomnia is a sleep disorder that affects the ability to fall asleep, stay asleep, or achieve restorative sleep. The impact of insomnia can be addressed by various sleep habits. The objectives of this study were to analyze the prevalence and behavioral factors of insomnia and the association between sleep hygiene and insomnia. Methods: A cross-sectional study was carried out among 384 Taman Beringin, Jinjang Utara residents. There are around 8,000 flats and 2,000 terrace houses in Taman Beringin. The survey, comprising insomnia and sleep hygiene questionnaires, was administered to the participant to assess behavioral factors and their related associations with sleep hygiene and insomnia. Result: Among the respondents, the majority (44.0%) experienced no insomnia, with 39.6% falling into the “Subthreshold” category. “Moderate” insomnia affected 14.3% of respondents, indicating a significant impact on insomnia, while “Severe” insomnia was least prevalent at 2.1%. Conclusion: The study revealed a significant association between behavioral factors and sleep hygiene and insomnia. Further research is needed to identify other factors that could strengthen the study’s effectiveness. Keywords: Insomnia, sleep hygiene, prevalence, associations, behavioral factors.
- ThesisRestrictedRISK FACTORS AND URINARY ANTIGEN TEST SENSITIVITY AND SPECIFICITY ANALYSIS FOR PAEDIATRIC PNEUMOCOCCAL PNEUMONIA IN THE EAST-COAST OF PENINSULAR MALAYSIA: A CASE-CONTROL STUDY.(International Medical University, 2024)Introduction: The high burden of paediatric pneumonia warrants investigation on its occurrence and risk factors, particularly among children aged five years old and below. Objectives: To determine the a) risk factors associated with paediatric pneumonia, b) occurrence of PCR positivity, c) sensitivity and specificity of pneumococcal urinary antigen test (UAT) in detecting pneumococcal pneumonia and d) colonisers among children aged five years and below in east-coast of Peninsular Malaysia. Methods: This case-control study was conducted over two years at the east-coast of Peninsular Malaysia. Cases were hospitalised children ≤5 years old with clinical and radiological diagnosis by sentinel site paediatrician while controls were children without any features suggestive of pneumonia. Nasopharyngeal swab for polymerase chain reaction (PCR) and urine samples for pneumococcal UAT were collected within 24 hours of admission. Results: Six hundred children, with mean age of 20.99 ± 15.35 months for cases and 21.57 ± 16.96 months for controls, were included in the study. Regression analysis revealed factors associated with pneumococcal pneumonia are children living in household of 3-5 occupants (OR, 1.821; 95%, CI 1.191-2.787, p=0.006), unknown history of hospitalisation (OR, 1.672; 95%, CI 1.034-2.703, p=0.036), and underaged children for vaccination up-to-age (UTA) (OR, 1.552; 95%, CI 1.013-2.378, p=0.044) were found to be significant factors among subjects. PCR testing revealed a positivity rate of 13.5% (n=81) among cases and 5.2% (n=31) among controls, accounting 18.7% (n=112) of all subjects. Additionally, UAT testing showed positivity rate of 8.7% (n=52) cases and 6.8% (n=41) controls, comprising 15.5% (n=93) of the subjects. The sensitivity and specificity of UAT were 38.4% and 89.8% respectively with positive predictive value (PPV) of 46.2% and negative predictive value (NPV) of 86.4%. UAT sensitivity and specificity among cases were 37% and 90% respectively while PPV of 57.7% and NPV of 79.4%. UAT sensitivity and specificity among controls were 41.9% and 89.6% respectively while PPV of 31.7% and NPV of 93.1%. Conclusion: Emphasise on risk factor prevention should be the preference over clinical management. Surveillance on local aetiology is essential. UAT was found to be an unsuitable rapid tool in diagnosing pneumococcal pneumonia nor detecting colonisers in paediatrics. Thus, research focus on higher valency vaccines production and invention of simpler, rapid, and non-invasive diagnostic method to reduce disease burden and improve disease prognosis.
- ThesisRestrictedMENTAL HEALTH LITERACY AND ITS ASSOCIATED FACTORS AMONG MYANMAR MIGRANT WORKERS IN KLANG VALLEY, MALAYSIA.(International Medical University, 2024)Introduction : According to the World Health Organization(WHO), mental health issues are surging throughout the world with 13% increase, predominantly caused by demographic shifts. Migrant workers face a variety of vulnerabilities that increase their risk of poor mental health. The objective of this study is to determine the level of knowledge, help-seeking behaviour and stigma towards mental health among Myanmar migrant workers as well as the correlation between sociodemographic factors, previous mental health experience, social support and the level of mental health literacy. Methods : A cross-sectional study design will be employed for this research. A convenience sampling will be utilized on selected clusters of Myanmar migrant workers population within Klang Valley. Results : The study drew a total of 395 qualified participants. The majority of respondents were between the ages of 18 and 32, male, Buddhist who had completed secondary level of education with a monthly family income of Rm1000 to Rm3000. The overall mean (SD) mental health literacy score was low 94.43 (9.563) and substantially related to gender, income and visit to mental health practitioner (p>0.05). Multiple linear regression model demonstrated that education level and past experience in visiting mental health practitioner were associated with mental health literacy (p>0.05). Conclusion : Overall mental health literacy levels were low and varied across sociodemographic categories. However, it was observed that attitudes that promote the recognition or appropriate help-seeking behaviour was high while knowledge of self-treatment was low among the respondents. Thus, addressing mental health literacy factors is a step towards developing a vulnerable demographic group with appropriate MHL, allowing them to maintain and preserve a good state of mental wellness. Further study on mental health literacy and its correlation with mental health outcome among Myanmar migrant workers would be beneficial in order to gain a better understanding of psychological difficulties and their influence on overall health.
- ThesisRestrictedSPIRITUALITY AND ASSOCIATED FACTORS IN COPING WITH STRESS AMONG NON-GOVERNMENTAL ORGANIZATIONS IN MALAYSIA.(International Medical University, 2024)Background: The relationship between spirituality and stress has been documented in the literature. This study aimed to determine the relationship between spirituality and stress and other associated factors among non-governmental organizations in Malaysia. Method: A cross-sectional study was conducted of 241 personnel from non-governmental organizations registered with the National Coalition for Mental Wellbeing (NCMW). The participants, including NGO employees, completed a self-administered online questionnaire. The survey included questions about sociodemographic and job-related factors. Stress levels were evaluated using the Perceived Stress Scale 10 (PSS-10) Questionnaire. Together, spiritual well-being was evaluated through 10 items from the Existential Well-Being Scale (EWB) incorporated within the Spiritual Well-Being Scale (SWBS). Results: The study found that a majority of NGOs (68.9%) reported moderate stress, with 18.1% experiencing low stress and 13.2% facing high perceived stress. Significant predictors of stress included age (P = 0.007), spirituality (P = 0.000), income satisfaction (P = 0.048), job satisfaction (P = 0.005), marital status (P = 0.026), and living status (P = 0.010). Conclusion: Contributors to stress among NGOs include age, spirituality, income satisfaction, job satisfaction, marital status and living status. Higher spirituality, linked to a connection with a higher power, reduces stress. Further studies are required to explore spirituality's role and manifestation. Keywords: Spirituality, Stress, NGOs, Malaysia, Spiritual Well-Being Scale (SWBS), and Perceived Stress Scale (PSS).
- ThesisRestrictedEPIDEMIOLOGY OF FATAL AND NON-FATAL CHILDHOOD DROWNING IN MALAYSIA: 2000-2022 A SECONDARY DATA ANALYSES(International Medical University, 2024)Objectives: This dissertation studied the time trends and distribution of fatal and non-fatal childhood drowning in Malaysia by demographic and spatial factors between 2000 and 2022. The difference in annual incidence between 2000-2011 and 2012-2022 was also identified. Methods: The drowning data reported to the national Health Informatics Centre (HIC) for 18 years old and below, from hospitalised cases of child drowning incidents and drowning deaths, were analysed. Data from the Department of Statistics Malaysia (DOSM) were also retrieved. These data were then used to calculate annual incidence, annual rates of change in drowning, and case fatality rates. Also, binary logistic regression analyses identified the socio-demographic and spatial factors associated with drowning. The outcome or the dependent variables were fatal and non-fatal, while age, year, sex, race, and region acted as independent variables. Results: A total of 4,191 reports of childhood drowning incidents and 155 drowning fatalities were reported to HIC. Drowning incidence rate was higher in 2000-2011 (IR 21.83) than in 2012-2022 (IR 17.65). Drowning incidence were significantly higher among the aged 0-4 years, boys, Bumiputera, and children living in urban areas (p<0.001). In contrast, the case fatality rate was higher in 2012-2022 (CFR 4.88) than in 2000-2011 (CFR 2.75). Children aged 0-9 years (p<0.001), children living in the Klang Valley region (p=0.049), and urban areas (p=0.034) were significant in fatal drowning. The time trends analysis for annual rates of change increased by 0.0001 for drowning incidents and 0.0003 for drowning fatalities. The east coast region significantly demonstrates 2.19 times (95% CI 1.03-4.65) higher than other regions (p=0.0041). Conclusions: This study provided more detail analyses of available childhood drowning data. The null hypothesis was rejected as there was a difference of drowning incidents in 2000-2011 and 2012-2022. The findings also suggested that preventive measures should be targeted towards children aged 0-9 years, boys, and children living in urban areas.
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- ThesisRestrictedIDENTIFICATION OF EFFECTIVE DRUGS OR DRUG COMBINATIONS TARGETING NON – STEM BREAST CANCER CELLS AND BREAST CANCER STEM CELLS(International Medical University, 2016)Breast cancer stem cells (BCSCs), as a subset of cancer cells with enriched capacity to generate breast tumors, have recently been attributed to driving cancer recurrence and metastasis. Although the importance of developing strategies to target BCSCs has been highlighted, it is conceivable that the depletion of BCSCs within a breast tumor would not lead to complete regression since non-BCSCs might still be capable of sustaining tumor growth or regaining BCSC potential. As either of these possibilities would confound the effectiveness of therapeutic agents that exclusively target BCSCs, this study aimed to develop combinatory therapeutics that apply agents targeting both BCSCs and non-BCSCs. By utilising parental cells and mammospheres as screening platforms, a total of 193 candidate molecules were identified as potent hit compounds inhibiting both BCSCs and non-BCSCs. Subsequent analysis suggested histone deacetylase (HDAC) inhibitors as a class of anti-cancer agents targeting both BCSCs and non-BCSCs. When combined with conventional chemotherapeutics, HDAC inhibitors were found to synergise DNA-damaging chemotherapeutics, namely doxorubicin and cisplatin, against BCSCs and non-BCSCs derived from MDA-MB- 468; whereas their combined treatment with anti-mitotic chemotherapy, namely paclitaxel, only exerted synergy in MDA-MB-468 non-BCSCs. Intriguingly, neither pan-HDAC, hydroxamate-based inhibitor nor class I specific, benzamide-based HDAC inhibitor was superior to be combined with conventional chemotherapeutics against these BCSCs and non-BCSCs. Further evaluations indicated that quisinostat, as the most potent HDAC inhibitor tested, managed to enhance the doxorubicininduced cytotoxicity in both BCSCs and non-BCSCs derived from different subtypes, including basal-like triple negative breast cancer (TNBC) subtypes (MDA-MB-468 and HCC38), mesenchymal-like TNBC (MDA-MB-231), and luminal-like breast cancer (MCF-7). Conversely, the synergism between quisinostat and cisplatin was TNBC subtype-dependent. Also, it was observed that both BCSCs and non-BCSCs of TNBC subtypes were more sensitive to the co-treatment of quisinostat with DNA damaging chemotherapeutics, as compared to luminal-like breast cancer subtype. Moreover, the dose reduction potentials of these combinatory regimens that revealed in this study may be exploited to reduce the dose-limited toxicities in clinical oncology. In summary, this study offered HDAC inhibitors as novel therapeutic options, either as monotherapy or combination therapy, for refractory breast cancer treatment which warrants detailed investigations.
- ThesisRestrictedMethodological Quality And Concordance Of Recommendations Across Clinical Practice Guidelines For The Management Of Hypertension In Southeast Asia(International Medical University, 2021-05)Background The regional epidemic of hypertension in Southeast Asia indicates an important role for clinical practice guidelines (CPGs) to optimize its management. This study aimed to evaluate the methodological quality and the rate of concordance of recommendations across the CPGs in Southeast Asia with internationally reputable CPGs. Methods CPGs for the management of hypertension in Southeast Asia were retrieved from the websites of Ministry of Health or cardiovascular specialty societies of the individual countries during November to December 2020. Two reviewers independently appraised the methodological quality of all the included CPGs using the Appraisal of Guideline ResEarch and Evaluation instrument. The recommendations for the management of hypertension specified in the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guideline and the 2018 European Society of Cardiology (ESC)/European Society of Hypertension (ESH) guideline were selected to be the reference standards; the recommendations concerning the management of hypertension in the included CPGs in Southeast Asia were assessed if they were concordant with the reference recommendations. Results We identified six CPGs for the management of hypertension in Southeast Asia. Upon quality appraisal, except for the CPG originated from Malaysia which could be “recommended” for use in practice, the remaining five CPGs could only be “weakly recommended”. Considering the six included CPGs from Southeast Asia, concordance was observed for 30 out of 59 (50.8%) reference recommendations generated from the 2017 ACC/AHA guideline and for 31 out of 51 (69.8%) reference recommendations derived from the 2018 ESC/ESH guideline. Conclusion More efforts should be invested to improve the methodological quality of the CPGs for the management of hypertension in Southeast Asia. While the CPGs in Southeast Asia have a high rate of non-concordance with internationally reputable CPGs, the concordant recommendations could perhaps be considered a standard of care for the regional management of hypertension in Southeast Asia. Keywords: AGREE II; CPG; Guideline; Hypertension; Recommendation
- ThesisRestrictedInhibition Of Cancer Cell Proliferation And Survival Through Synergistic Effects Of Traditional Anti-Cancer Drug Action In Combination With Targeted Knockdown Of Cancer-Related Genes(International Medical University, 2012)Chemotherapy remains as the option for treating cancer in increasing the lifetime of the patient. The severe effects of chemotherapy drugs contribute to the developments of approaches based on silencing of cancer-causing genes using siRNA. Nonetheless, siRNA delivery vehicle is needed as they cannot diffuse across cellular membranes; thus leading to the development of carbonate apatite nanoparticle. By employing carbonate apatite nanoparticles, we showed that codelivery of siRNAs and drugs managed to block signalling pathways. Simultaneous delivery of ROS1 siRNA and 40nM Pax by carbonate apatite exhibited better effects in MCF7 cells where the cell viability was significantly reduced to 26% with 42% more sensitive towards the drug. Further analysis showed the treatment caused the disruption of phosphorylation in ERK1/2 pathway. Besides, silencing of RAF1 gene concurrently with 40nM Dox in MCF7 cells also resulted in low cell viability and relatively high enhancement of chemosensitivity, but this co-treatment did not affect the phosphorylation of ERK1/2 pathway. GRB2 gene seemed to be vital in MCF7 as its knockdown showed prominent cell death and chemosensitivity towards 8nM Pax, 40nM Pax and 40nM Cis. Nevertheless, all these three combinations failed to block the phosphorylation of ERK1/2 pathway. In 4T1 cells, co-delivery of SHC1 siRNA and 8nM or 40nM of Pax greatly decreased the cell viability to 29% and 17% respectively owing to the high sensitivity towards drug. Moreover, co-treatment of ROS1 siRNA and 40nM Dox reduced cell viability to 30% with the sensitivity for the drugs increased by 51%. Western blot results proved that this treatment had successfully blocked the phosphorylation of AKT1 (Ser473) pathway while partially blocked the phosphorylation of ERK1/2. From the in vitro results, treatment of ROS1 siRNA and Dox demonstrated effective cytotoxicity as well as interruption in AKT1 (Ser473) and ERK1/2 pathways. Thus, this combination was then used in in vivo study. Intratumoural injection of carbonate apatite conjugated with ROS1 siRNA and Dox also blocked the phosphorylation of AKT1 (Ser473) pathway. This concluded that carbonate apatite can be a promising tool for both in vitro and in vivo delivery of siRNAs targeting important cancer-related genes.
- ThesisRestrictedCINNAMOMUM, ITS ANTIBACTERIAL EFFECTS AND CINNAMOMUM IMPRESSICOSTATUM, IDENTIFICATION OF BIOACTIVE CONSTITUENTS AND POSSIBLE MECHANISMS OF ACTION AGAINST METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS(International Medical University, 2014-03)The emergence of Methicillin Resistant Staphylococcus aureus (MRSA) which is resistant to many available antibacterial agents, especially the β-lactam antibiotics, has become a major threat to the health sector worldwide, giving impetus to the search for novel antibacterial agents efficacious against this bacterium. Four (4) Cinnamomum species i.e. C.iners, C.altissimum, C.impressicostatum and C. porrectum were investigated against a range of multidrug resistant bacteria, including Methicillin Resistant Staphylococcus aureus, our main subject of interest, for potential antibacterial activity and elucidation of their modes and mechanisms of action. Characterisations of their bioactive fractions were performed using bioassay guided isolation techniques. C.impressiscostatum stem-bark extract recorded the highest zone of inhibition and lowest minimum inhibitory concentration against MRSA. The presence of salt enhanced the killing efficiency of the plant extract against MRSA. Cellular materials leaked from MRSA after treatment with the plant extract and this was concomitant with marked cell wall damage, as observed using scanning electron microscopy (SEM). A total of 136 genes were found to be differentially regulated by C. impressicostatum stem-bark extract. Amongst these, 73 genes were upregulated and 63 genes were downregulated. The MRSA genes that fluctuated in expression when treated with the plant extract involved various pathways, such as amino acid metabolism, carbohydrate metabolism, lipid metabolism, nucleotide metabolism, membrane transport, metabolism of cofactors and vitamins, metabolism of terpenoids and polyketides, biosynthesis of secondary metabolites, energy metabolism, folding, sorting and degradation, glycan metabolism, pathways in pathogenesis, replication and repair, signal transduction, transcription, translation, translational ribosomal structure and biogenesis and xenobiotic degradation and metabolism. The possible mechanisms underlying the killing action of C.impressicostatum active fraction of water extract against MRSA are via inhibition of biofilm formation, inhibition of nucleotide metabolism as well as DNA replication and repair, downregulation of the mismatch repair mechanism, thereby enabling maintenance of deleterious and lethal mutations, ultimately causing cell death, induction of increased cellular vulnerability to the effects of reactive oxygen and nitrogen species, inhibition of essential lipid biosynthesis required for cellular structure and metabolism as well as the induction of apoptosis.
- ThesisRestrictedALLERGENIC POTENTIAL OF THREE AIRBORNE ALGAE AND CYANOBACTERIA ISOLATED FROM AN OFFICE BUILDING IN KUALA LUMPUR(International Medical University, 2017)Airborne algae and cyanobacteria (AAC) have received much attention as their occurrence have been documented in several studies, including indoor environment. There has been concern whether AAC can trigger allergic response and thus, they may have ill health effects, especially in relation to sick building syndrome (SBS). There have been very few studies reported on the allergenicity of AAC. The main objective of this study was to assess the allergenic potential of three AAC, namely Scenedesmus sp., Cylindrospermum sp. and Hapalosiphon sp.1, which were isolated from an office building in Kuala Lumpur. The study was based on a mouse model, with the suspension of AAC powder in phosphate buffered saline (PBS) administered via nasal route. Naïve mice were sensitised to 1 mg/mL of AAC for 10 consecutive days during Phase I immunisation. In Phase II immunisation which was given after five resting weeks, the mice were re-challenged with 20 μL of AAC at two concentrations (0.01 and 1 mg/mL) for three consecutive days before they were sacrificed. The immune response was assessed based on white blood cell profiles, quantification of humoural and intracellular expression of IgE, TH2 predominant and inflammatory cytokines and histopathological examination. In general, the three AAC elicited greater immune response in mice challenged with high (1 mg/mL) concentration of AAC than with low (0.01 mg/mL) concentration. In mice challenged with Scenedesmus sp. at both low and high concentrations, there were elevated peripheral eosinophil and monocyte counts. Significantly higher levels of serum IgE (P<0.05) and IFN-γ (P<0.05) compared to negative control were also observed. The data collected 48 h after the last dose of immunisation also indicated possible cause of allergic airway inflammation, a chronic manifestation of respiratory allergy upon nasal exposure to the algal particles. On the other hand, Cylindrospermum sp. and Hapalosiphon sp.1 did not elicit type-1 hypersensitivity as both eosinophil counts and serum IgE levels were not elevated in the sensitised mice. The results suggest that the two airborne cyanobacteria provoked immune response differently. In mice challenged with Cylindrospermum sp. (1 mg/mL), there were elevated serum IL-4 (22.1 pg/mL, P<0.05). However, the increase in peripheral neutrophil counts (9.2%) against Cylindrospermum sp. (1 mg/mL) was not significant when negative control was compared. In comparison, in mice challenged with Hapalosiphon sp.1, there were elevations of serum IL-6 (4.8 pg/mL, P<0.05) yet the observed increase of peripheral lymphocyte counts (9.2%) was not statistically significant. In addition, the elevations in serum IFN-γ levels were highest in mice nasal challenged with Cylindrospermum sp. (71.9 pg/mL, P<0.05), followed by Hapalosiphon sp.1 (50.6 pg/mL, P<0.05). Taken together, the results suggest that nasal exposure to Cylindrospermum sp. and Hapalosiphon sp.1 may provoke inflammatory immune responses in the airway. Further studies are warranted to assess the potential health impact due to the allergenic potential of the AAC, especially with regards to the effect of continual exposure to low concentration of the algal particles over extended period of time.