Saudi Cultural Missions Theses & Dissertations
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Item Restricted Investigating the Role of Zinc in Manganese-induced Hepatotoxicity(Florida International University, 2024) Alandanoosi, Afnan; Liuzzi, Juan; Palacios, Cristina; Narayanan Vijaya; George, FlorenceThe objective of this study was to investigate the role of zinc (Zn) status in manganese (Mn) -induced hepatotoxicity using epidemiological data and vitro experiments. First, we conducting epidemiological study using the National Health and Nutrition Examination Survey (NHANES) to determine the relationship between Zn status and blood Mn levels on enzymatic markers of liver damage. The findings indicated that without the regression interaction of Zn intake or serum Zn, blood Mn exhibits a direct (positive) association with Alkaline Phosphatase (ALP) and Aspartate Amino transferase (AST). The results however showed that with the interaction of blood Mn and Zn intake at the second quartile (Q2) (marginal low Zn intake), a negative association was found with ALP in model 1,model 2 (corrected by age and gender), and model 3 (corrected by age, gender, race, education, BMI, alcohol, smoking and diabetes ). A similar association was found between Q4 (adequate/high Zn intake) and Lactate Dehydrogenase (LDH) activity in all three models of the study. Second, the effect of Zn deficiency and adequacy on Mn toxicity and the expression level of the cellular Mn efflux transporter SCL30A10 in human hepatocytes was evaluated. Mitochondria oxidative stress, apoptosis, and cell death and proliferation studies showed that exposure to elevated levels of Mn increased oxidative stress, apoptosis, and cell death. Mn exposure also decreased cell proliferation. Noteworthy, Zn depletion was found to enhance Mn induced apoptosis and cell death. Lastly, the mRNA expression of SLC30A10 was significantly decreased by Mn exposure (p < 0.05). However, no significant difference in the protein expression level of SCL30A10 was found. This suggests that there was no compensatory regulatory response of this transporter expression to either Zn deficiency or Mn exposure for the time point analyzed. Overall, the results from the epidemiological data and in vitro studies indicate that Zn deficiency could enhance the toxic effects of Mn. The results underscore the importance of having an adequate Zn intake in mitigating Mn induced cytotoxicity.63 0Item Restricted Epidemiology of Cerebral Palsy in the Kingdom of Saudi Arabia(The University of Sydney, 2024-05-31) Mushta, Sami Mukhdari E; Khandaker, Gulam; McIntyre, Sarah; Rashid, Harunor; Badawi, NadiaBackground: Cerebral palsy (CP) is the primary cause of childhood physical disability and lacks comprehensive epidemiological data in Saudi Arabia and similar regions. This PhD thesis explores the epidemiological profile, clinical manifestations, and challenges of CP in Saudi Arabia, aiming for a better understanding and potential intervention strategies. Methods: This thesis utilised multiple research methods: - Narrative literature review to define the burden of CP in Arabic-speaking and Middle Eastern countries. - Systematic reviews, meta-analyses, and a hospital-based surveillance of children with CP in Saudi Arabia from 2020 to 2022 to assess epidemiology and nutritional status. - An online survey to examine the impact of COVID-19 on primary caregivers of children with CP in Saudi Arabia. - Designing and establishing a CP register in Saudi Arabia through multi-organisational collaboration. Results: Literature reviews indicate scant data on CP epidemiology in the Middle East, including a CP prevalence of 1.8/1000 live births in the region. Spastic CP is predominant (59.8%), with significant consanguinity-related risk (37.7%). In Saudi Arabia and similar regions, 71.5% of children with CP suffer from malnutrition. Surveillance of 442 children indicated a majority are over four years old, with birth asphyxia being a major cause (32.4%). Many children lacked rehabilitation services and were not current on immunizations. COVID-19's impact was notable but mostly non-hospitalised; however, telehealth was deemed inadequate by most families. Conclusions: CP epidemiology in Saudi Arabia is poorly defined despite being a high-income country. Significant gaps in population-based surveillance and research persist, underscoring the need for comprehensive studies to understand CP's aetiologies and improve prevention, diagnosis, and treatment. Establishing a Saudi CP register is crucial for advancing research and healthcare strategies.28 0Item Restricted Exploring diagnostic approaches and quality assurance data for improved management of gonorrhoea antimicrobial resistance(The University of Queensland, 2023-05-03) Alharbi, Bushra; Trembizki, Ella; Whiley, David; Sweeney, Emma; Lord, MaggyNeisseria gonorrhoeae (NG), the etiological agent of gonorrhoea, accounts for 82 million cases among the 374 million new sexually transmitted infections recorded in 2020. NG is associated with high rates of antimicrobial resistance (AMR), with the World Health Organization designating it as an urgent AMR threat. There are several important factors when it comes to the ideal management of NG. One important approach to NG management entails enhancing AMR surveillance capabilities. Another involves applying accurate and specific diagnostics to detect both NG and related AMR genes/mutations directly from clinical samples, which can then guide treatment and/or inform surveillance. To effectively enhance surveillance of NG and associated AMR, it is crucial to comprehensively understand the factors that influence NG’s infection rates, distribution, and prevalence throughout geographic regions. Such knowledge contributes to effective public health interventions. Among the various public health concerns relevant to NG, COVID-19 has been a significant recent event to indirectly impact NG prevalence and transmission. Consequently, this thesis included an examination of the impact of COVID-19-related public health measures on the prevalence of NG and the distribution of NG genotypes among the population of Queensland (QLD) during the first half of 2020 (Chapter 2). The results of this chapter showed that there is a decrease in NG genotypic diversity post COVID-19 in 2020 in QLD, and the proportion of the isolates carrying an azithromycin AMR specific determinant have almost doubled post COVID-19. In Australia, NG treatment guidelines in most settings indicate 500 mg of ceftriaxone intramuscularly and 1 g of azithromycin orally to be the standard of care. However, the increase in azithromycin resistance has prompted a re-evaluation of this therapy regimen elsewhere, with 1 g of azithromycin no longer being recommended as a first-line therapy in many countries worldwide. This shift emphasises the importance of further understanding the spread of azithromycin resistance in Australia to inform its use as a first-line therapy. To do so, complementing culture-based surveillance by directly applying molecular AMR tests on clinical samples is required. As NG is known to constantly evolve, target testing variations may arise. It is therefore important to ascertain which genes and mutations are most prevalent and informative of azithromycin AMR. Accordingly, as part of this study (Chapter 3), the Pathogen-Watch online genomic database was explored to determine the prevalence of mutations known to be associated with azithromycin resistance within the global collection of NG isolate sequences. These outcomes then informed which diagnostic targets are most relevant when it comes to molecular assay targets; the meningococcal-mtrR and 23S-rRNA were found most significant. Following the above, real-time polymerase chain reaction (PCR) assays were developed and applied on NG-nucleic acid amplification test (NAAT)-positive clinical samples to enhance culture-based surveillance and better elucidate the distribution and prevalence of azithromycin resistance in QLD (Chapter 4). The results of this chapter indicated that there is a reduction in 23S rRNA determinants, while an increase the prevalence of meningococcal-mtrR harbouring strains (reinforcing Chapter 2 isolate data post COVID-19) which could put azithromycin treatment at risk in QLD. Molecular assay design complexities arose due to cross-reactivity with commensal Neisseria species, particularly for pharyngeal clinical samples. As routine molecular NG-AMR testing is on the horizon, I explored potential testing bias that may arise if patient pharyngeal clinical samples are excluded from the testing algorithm (Chapter 5). The results of this chapter suggested that excluding pharyngeal samples from N. gonorrhoeae AMR molecular testing in QLD will be of minimal impact with a loss of 13.17% of samples with the majority of infections appearing in two or more anatomical sites, therefore mostly accounted for. Finally, rapid and cost-effective diagnosis of both NG and AMR represents an important measure for controlling and managing gonococcal infection. Diagnostic tools such as PCR and culture require access to laboratory facilities and are associated with high costs and expertise, unfeasible in resource-poor settings with syndromic patient management. Therefore, alternative cost-effective diagnostic tools are urgently required. To further explore the latter as well as attempt to resolve commensal Neisseria cross-reactivity, I investigated the utility and feasibility of near-infrared spectroscopy (NIRS), for the identification and differentiation of NG from commensal Neisseria and detection of AMR (Chapter 6). This proof-of-concept study demonstrated the capability of the NIRS to distinguish N. gonorrhoeae from Neisseria commensals with accuracy of 98% for N. gonorrhoeae and 96% for commensals. Further, N. gonorrhoeae fully-susceptible strains were distinguished from resistant strains with an accuracy of 86% and 90%, respectively. The data from this work reinforces how molecular methods enable to enhance culture-based surveillance in QLD to capture less represented regions and populations. Importantly, this data demonstrated that azithromycin use as a blanket therapy for NG in QLD may be undermined due to a significant increase of AMR determinants in local NG. The exclusion of pharyngeal samples from molecular AMR testing is unlikely to affect the representativeness of AMR in our population, yet this needs to be carefully monitored. The exploration of NIRS technology as an alternative test for NG and AMR detection is feasible, yet further validations are required. This body of work represents better understanding of the spread of NG-AMR in QLD and further informing potential gaps when rolling out molecular AMR testing in our population. Finally, paving the way for the development of alternative, rapid and cost-effective diagnostics to be further explored.43 0Item Restricted Sex Differences in The Epidemiology of Cardiovascular Health Over The Life Course(Saudi Digital Library, 2023-11-09) Shah, Mohammad; Gall, Seana; Tian, Jing; Busoct, Marie-JeanneBackground: Studies found that there are sex differences in cardiovascular diseases with a greater incidence among men as compared to women. The reasons for these differences are currently poorly understood. Potential reasons include differences between men and women in the prevalence of sociodemographic, lifestyle, psychosocial or biomedical risk factors for cardiovascular diseases over the life course; the magnitude or direction of association between cardiovascular risk factors and cardiovascular health; using healthcare services for the diagnosis, prevention or management of cardiovascular diseases or its risk factors. Understanding these differences might help to develop better sex-specific health prevention strategies over the life course to reduce sex differences in cardiovascular health at adulthood. Therefore, the aim of this PhD is to examine sex differences in cardiovascular health over the life course. Aims: The aims of this thesis were to (1) examine changes over time in the prevalence of cardiovascular health and cardiovascular risk factors in different age groups among men and women, (2) examine the contribution childhood socioeconomic, psychosocial, lifestyle and biomedical risk factors to sex differences in carotid artery plaques and Intima Media Thickness (IMT) in adulthood, (3) explore sex differences in the association between stroke risk factors at early adulthood with carotid artery plaques, IMT and carotid distensibility at mid-adulthood and (4) examine sex difference in the use of health services for the diagnosis and management of cardiovascular diseases and diabetes from young to mid-adulthood. Methods: This thesis contains four chapters presenting studies addressing these aims. Aim 1: Data were from participants aged 18 years and older from the Australian National Health Surveys (NHS) in 2011-12 (N=15,339), 2014-15 (N=12,297) and 2017-18 (N=13,930). Sociodemographic, health-related and biomedical factors were collected from men and women in younger, middle and older ages. Cardiovascular health score based on five key risk factors including smoking, blood pressure, physical activity, diet and Body Mass Index (BMI) were calculated with items scored 0 (poor), 1 (intermediate) or 2 (ideal). Cardiovascular health scores summed items and was categorised (low [0-4], middle [5-6], high [7-10]). Sex-specific trends in cardiovascular health over time were examined with multinomial logistic regression to estimate the Relative Risk Ratio (RRR ± 95% CI) adjusted for sociodemographic factors comparing data collected in 2014-15 and 2017-18 to 2011-12. We also used sex-specific log binomial regression to estimate the Relative Risk (RR± 95% CI) to examine the trends for the prevalence of each ideal risk factor in 2014-15 and 2017-18 compared to 2011-12. Aim 2: Children in the 1985 Australian Schools Health and Fitness Survey were followed up in the Childhood Determinants of Adult Health (CDAH) study at the age 36-49 years (2014- 19, n=1,085-1,281). Log binomial and linear regressions examined sex differences in adult carotid plaques (n=1,089) or carotid IMT (n=1,281). Childhood sociodemographic, psychosocial and biomedical risk factors that might contribute to sex differences in carotid IMT/plaques were examined using purposeful model building with additional adjustment for equivalent adult risk factors in sensitivity analyses. Aim 3: Participants in the Australian CDAH study at baseline aged 26-36 years (2004-06, CDAH-1) were followed-up at 39-49 years (2014-19, CDAH-3). Baseline risk factors included smoking, fasting glucose, insulin, systolic blood pressure (SBP) and diastolic blood pressure (DBP). Carotid artery plaques, IMT and distensibility were assessed at follow up. Log binomial and linear regression with risk factor*sex interactions predicted carotid measures. Sex-stratified models adjusting for confounders were fitted when significant interactions were identified. Aim 4: Participants were from the Australian CDAH observational cohort study at baseline aged 26-36 years. Diagnostic and therapeutic Medicare health services for cardiovascular disease and diabetes were collected in a period of approximately 10 years following CDAH1. We used log binomial regression analyses to examine sex differences in using health services. We then examined the contributions of other factors to these sex differences by adjusting for potential covariates in the final models based on the purposeful model building. Results: Aim 1: Men had worse overall and individual cardiovascular risk factors compared to women in each survey. There were a few changes in cardiovascular health over time for most age and sex groups. There was a lower prevalence of ideal cardiovascular health in middle-aged and older men and intermediate cardiovascular health in middle-aged women in 2017-18 compared to 2011-12. Young men and women more often had ideal diet and smoking status, yet lower prevalence for ideal BMI in 2017-18 as compared to 2011-12. Middle-aged and older men less often had ideal blood pressure in 2017-18 as compared to 2011-12. Aim 2: Among 1,281 and 1,081 participants who had complete data of carotid IMT and carotid plaques respectively, women less often had carotid plaques (10%) than men (17%). The sex difference in the prevalence of plaques was reduced by adjustment for childhood school achievement and SBP. Additional adjustments for adult education and SBP further reduced sex difference. Women (mean ± SD 0.61 ± 0.07) had thinner carotid IMT than men (mean ± SD 0.66 ± 0.09). The sex difference in carotid IMT reduced with adjustment for childhood waist circumference (WC) and SBP and further reduced with adjustment for adult WC and SBP. Aim 3: Among 779 participants with complete data (50% women), there were significant interactions of smoking, SBP and glucose with sex in the associations with carotid measures at follow-up, with associations being significant in women only. Current smoking was associated with the incidence of plaques, which reduced when adjusted for sociodemographic factors, depression, and diet. Greater SBP was associated with lower distensibility adjusted for sociodemographics. Greater glucose was associated with lower distensibility, which decreased when adjusted for sociodemographics, blood pressure, depression and polycystic ovary syndrome. Aim 4: Among those who provided consent to access universal health insurance claims data (men, n=1,222 and women, n=1,636), women more often used health services (42% vs. 35%, RR 1.20 95% CI 1.09, 1.32), especially diagnostics (38% vs. 34%, RR 1.11 95% CI 1.00, 1.24) than men. Exploration of the demographic, social, economic, psychosocial and healthrelated factors that may explain the higher use in women compared to men, suggested that diet, drinking alcohol and having a family history of cardiovascular disease decreased these sex differences. Conclusion: Sex differences in cardiovascular health are evident over the life course. Women have better cardiovascular health in terms of cardiovascular risk factors and structure/function (e.g. carotid plaques, IMT and distensibility) as compared to men. Various sociodemographic, behavioural and lifestyle and biomedical factors over the life course partially explained sex differences in cardiovascular health. This included that women use more health services related to the identification and management of cardiovascular diseases than men, which was partially explained by their healthier lifestyles as compared to men. Somewhat contrary to these findings was that there were some risk factors at early adulthood that were less prevalent yet were more strongly associated with cardiovascular health in women than men. The thesis has demonstrated the complexities of sex differences in cardiovascular health over the life course. The findings suggest the potential for actions targeting sex differences in cardiovascular health, particularly risk factors, at all stages of the life course. The potential for sex-specific strategies targeting health behaviour, health literacy and engagement with preventative health services from early to mid-adulthood onwards should be tested to see if they enhance the primary prevention of cardiovascular diseases in both men and women.34 0Item Restricted 24-Hour Movement Guidelines and Cardiorespiratory Fitness in Relation to Cardiovascular Disease Risk Factors in Adolescents from Saudi Arabia(University of Exeter, 2022) Alkhraiji, Mohummed Hamad; Williams, Craig A; Barker, Alan RPhysical activity in the form of moderate-to-vigorous physical activity (MVPA), sedentary behaviour in the form of recreational screen time (ST), and sleep, are individually associated with cardiovascular disease (CVD) risk factors in adolescents. Commonly, researchers investigate these three movement behaviours in relation to CVD risk factors in isolation. However, after the launch of the Canadian 24-Hour Movement Guidelines for children and youth, there have been calls to integrate all three 24-hour behaviours (PA, ST, & sleep). Furthermore, a scientific statement from the American Heart Association highlights the importance of cardiorespiratory fitness (CRF) as a measurement for health screening in children and adolescents as CRF is a strong predictor of CVD risk. Previous studies have individually explored how the 24-hour movement guidelines or CRF are associated with CVD risk factors in adolescents; however, which of the two (24-hour movement guidelines or CRF) is more strongly associated with CVD risk factors in adolescents is unknown. Currently, most studies have been conducted in North America and Europe, with the Middle East neglected, including Saudi Arabia, which has a very different lifestyle, environment, climate, school system, and culture compared to North America and Europe. Therefore, to address this gap in the literature in the context of Saudi Arabia, the studies included in this thesis aimed to investigate the prevalence of 24-hour movement guidelines and CRF and their relationship with CVD risk factors in adolescents from Saudi Arabia aged 12–15 years old. Chapter 4 narratively reviewed movement guidelines and CRF in relation to CVD risk factors in children and adolescents from the Gulf Cooperation Council Countries, which indicated gaps in the literature investigating the 24-hour movement guidelines. In addition, Chapter 4 highlighted that there is poor evidence for an association between single movement guidelines and CRF with multiple CVD risk factors; most studies have only examined associations with weight status. Chapter 5 examined the reliability and validity of using the Global School-Based Student Health Survey (GSHS) to assess the 24-hour movement guidelines in (n = 120; 50% females) adolescents aged 12–15 years old, from Saudi Arabia and found acceptable reliability and validity. In Chapter 6, the GSHS was used to examine the prevalence of the 24-hour movement guidelines and their associations with overweight/obesity in a sample of (n = 4224; 52% females) participants aged 12–15 years old. The results indicated that only 2.7% achieved the recommended 24-hour movement guidelines and highlighted weak, non-significant associations with the risk of overweight/obesity. In Chapter 7 a subsample of (n = 120; 50% females) participants aged 12–15 years old from the study in Chapter 6 underwent a 24-hour movement guidelines assessment using GENEActiv accelerometers (for MVPA and sleep) and the GSHS (for ST). In addition, CRF was assessed using the Progressive Aerobic Cardiovascular Endurance Run test, and fasting blood samples, blood pressure, and anthropometrics were collected. None of the adolescents in this subsample met all three of the 24-hour movement guidelines, and there were no favourable significant associations with individual or clustered CVD risk factors. In addition, few males (16%) and almost half of the female (46.3%) participants had a healthy CRF. However, in males only, having a CRF was significantly and negatively associated with waist circumference (WC) and clustered CVD risk. Collectively, the results presented in this PhD thesis contribute to enhancing the literature in four ways. Firstly, it demonstrates that there is a lack of studies on the 24-hour movement guidelines and CRF in relation to CVD risk factors for adolescents from the Gulf Cooperation Council countries. Secondly, it is the first study to examine a questionnaire for its reliability and validity to measure the 24-hour movement guidelines, which found an acceptable reliability and validity. Thirdly, it shows that via a questionnaire few adolescents (2.7%) from Saudi Arabia are meeting the 24-hour movement guidelines, which is not significantly associated with being at risk of overweight/obesity. Lastly, it shows that when using device-based accelerometry, none of the adolescents from Saudi Arabia are meeting the 24-hour movement guidelines, which is not significantly associated with individual or clustered CVD risk factors profiles in both sexes. Moreover, healthy CRF was not significantly associated with individual or clustered CVD risk factors in females, while in males, healthy CRF was only significantly and inversely associated with WC and clustered CVD risk factors. Based on the above findings, it is suggested that 24-hour movement guidelines are not favourable strongly associated with individual or clustered CVD risk factors in adolescents of both sexes from Saudi Arabia. In addition, in females it appears that there are no significant associations between CRF and individual or clustered CVD risk factors. Initiatives should be developed to encourage male adolescents from Saudi Arabia aged 12–15 years old to achieve a healthy CRF to reduce the risk of WC and clustered CVD risk factors. However, future longitudinal studies with larger sample sizes would enable further insight into the associations between 24-hour movement guidelines and CRF in relation to CVD risk factors in adolescents from Saudi Arabia and should provide specific recommendations for both sexes.26 0