Saudi Cultural Missions Theses & Dissertations
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Item Restricted The impact of Dairy- free diet on the management of Hypertension- A systematic review.(University of Nottingham, 2024) Alzubidi, Fatimah; McCullough, FionaIntroduction: Hypertension is a significant risk factor for chronic diseases, and its prevalence is increasing globally. The development of hypertension is influenced by genetic predisposition, environmental factors, age-related changes, and immunological influences. Dietary management plays a key role in managing hypertension, with the DASH diet being an effective intervention. Calcium intake through diet, particularly from dairy products, has been shown to help lower blood pressure. Previous studies have demonstrated a link between dairy consumption and decreased blood pressure. Aim: This paper aimed to systematically review the existing literature by comparing diets without dairy to those that include dairy, focusing on the effect of dairy exclusion on hypertension, which was the primary outcome, as well as on secondary outcomes, such as changes in lipid profile, weight, waist circumference, and glucose levels. Methods: PubMed, Scopus, Embase, and Web of Science were used to search for relevant articles that study the impact of dairy food exclusion on the management of hypertension. Only records that met the following inclusion criteria were considered: published between 2000 and June 2024, full text, and in English, focusing on adults aged ≥18 years of either gender, with or without health conditions. The Cochrane Collaboration quality assessment tool was employed to assess the included studies. Results: The results of six randomised clinical trials involving 462 adult participants indicated that a dairy-free diet did not have any discernible effect on both systolic and diastolic blood pressure measurements (in mmHg). Conclusion: This review indicates that eliminating dairy products from one's diet has no apparent impact on the incidence or management of hypertension despite the limitations of the included studies. Moreover, it emphasises the need for additional research to explore the effects of fat content and micronutrients on the management of hypertension.16 0Item Restricted Elucidation of the Role of Methylarginine Metabolism in Regulation of Nitric Oxide Production and Inflammation(University of Glasgow, 2024) Alshuwayer, Noha Ali S; Leiper, James; Mercer, JohnAtherosclerosis is a major global health issue, and inflammation is important in its pathogenesis. Many atherosclerosis risk factors lead to reduced nitric oxide (NO) bioavailability. Asymmetric dimethylarginine (ADMA), an independent cardiovascular disease risk factor and NO synthase inhibitor, is metabolised by dimethylarginine dimethylaminohydrolase (DDAH). DDAH2 is the isoform present in the immune system. A deeper understanding of ADMA metabolism could help reveal new therapies for atherosclerosis. However, it is debated if DDAH2 hydrolyses ADMA. There is evidence that DDAH2 has NO-independent cellular functions, and research in our group showed that DDAH2 regulates macrophage functions. This thesis initially aimed to investigate the role of DDAH2 in regulating inflammation in atherosclerosis models. However, this was derailed by limitations imposed by the Covid-19 pandemic. Therefore, models of inflammation were used. Genes and mechanisms associated with inflammation and atherosclerosis were investigated. RAW 264.7 murine macrophage cell line and bone marrow-derived macrophages (BMDM) were validated for suitability to study the DDAH-ADMA-NOS pathway. To better understand the functions of DDAH2, a macrophage-specific Ddah2 null mouse model was re-derived and validated. RNA sequencing data previously generated by our group from peritoneal macrophages of the same model was re-analysed and revealed almost 5,000 genes to be DDAH-dependent and required for normal immune response. More than 200 Reactome pathways appeared enriched, with apoptosis being the most enriched. The in silico data was validated in vitro in DDAH2-knockout peritoneal macrophages from the macrophage-specific Ddah2 null mouse model. Inferred hypotheses were investigated in DDAH2-Knockout BMDMs from the macrophage-specific Ddah2 null mouse model with confirmatory studies on C57BL/6J BMDMs using ADMA. The in vitro analysis in the BMDMs showed no conclusive evidence supporting the in silico data that DDAH2 regulates the investigated genes (except Il17a), nor did ADMA alter the gene response to LPS. Il17a was shown by the in silico analysis to be regulated by DDAH2 and was validated in vitro in peritoneal macrophages by both RT-qPCR and ELISA. Given the significant role of IL17A in inflammation and its existing use in treating systemic inflammatory conditions such as psoriasis, this thesis proposes DDAH2 as a potential therapeutic target for inflammatory diseases in general and atherosclerosis in particular.15 0Item Restricted Acute Remote Medicine Based Assessment of High Risk Atherosclerosis Patients(Imperial College London, 2024-07-21) Alshahrani, Nasser Saeed; Khamis, RamziAlthough there have been significant advancements in medical and interventional therapies, myocardial infarction (MI) remains a major cause of death in the UK. Unplanned readmission rates in the UK are high despite a global trend towards short hospital stays post-MI, sitting at approximately 10% at 30 days post-discharge and even higher at 6 months. The 30-day mortality rate post-ACS in the US is 7.3%, with comparably high rates observed in Europe and the UK. The use of telemedicine technology can provide remote, clinically necessary, diagnostic information, thus eliminating the necessity for patients to visit the hospital. Telemonitoring could improve the management of post-ACS care and reduce the number of unexpected readmissions. Despite these potential benefits, there are considerable barriers to its implementation. This thesis present four chapters discussing the impact and efficacy of home telemonitoring for cardiac patients post-ACS. I first used a systematic review and meta-analysis to investigate the existing research on the use of telemedicine for patient management post-ACS. Second, I designed and validated a clinical decision support system algorithm for the remote management of patients post-ACS in a nonhospital setting. Third, I conducted a randomised controlled trial (acronym: TELE-ACS) that used a specialised hybrid remote telemonitoring system to monitor patients following their hospital discharge post-ACS. Fourth, I conducted a 6-month cost-benefit analysis of the TELE-ACS protocol and assessed its impact on the health-related quality of life in patients following ACS. The results demonstrate that a remote monitoring approach in combination with clinical decision algorithm protocol based on patient symptoms, 12-lead ECG data, BP levels, and oxygen saturation levels, significantly decreased the rate of hospital readmissions, emergency department visits, unplanned coronary revascularisations, and patient-reported symptoms for patients post-ACS. Therefore, the TELE-ACS protocol represents a financially viable approach to reducing readmissions in ACS patients.23 0Item Restricted Systemic Inflammation, Arterial Stiffness, and Vascular Endothelial Dysfunction in Patients with Chronic Lung Disease(University of Dundee, 2024-05-22) Arafah, Abdullah M.; Khan, FaiselChronic lung disease (CLD) is considered a heterogeneous, complex, and multicomponent condition. Types of CLD include bronchiectasis, chronic obstructive pulmonary disease (COPD), and asthma. Cardiovascular events and peripheral vascular disease are highly prevalent among patients who are known to have CLD. It is increasingly acknowledged that cardiovascular comorbidities contribute to the disease’s severity. The underlying mechanisms that link CLD and cardiovascular disease (CVD) are inadequately understood. Systemic inflammation is a key component that could describe the link between CLD and CVD. Changes in vascular endothelial function accompany the increased cardiovascular events in CLD. Atherosclerosis and calcification of macrovascular and microvascular lead to further decrease vascular compliance. These structural changes in the vascular wall contribute to increased arterial stiffness observed in patients with CLD. Endothelial dysfunction and arterial stiffness are early signs of vascular disease and the development of cardiovascular events. Chronic systemic inflammation plays a vital role in linking CLD to the development of endothelial dysfunction and arterial stiffness. Therefore, this study aims to investigate the association between CLD and CVD. To successfully achieve the aims of this project, four work packages were employed, including a systematic review, a retrospective study, a Mendelian randomisation study, and a cross-section study involving the BRIDGE study. The systematic review study related to arterial stiffness in patients with CLD using various pulse wave velocity (PWV) methods, which assessed and summarised the outcomes of all relevant studies regarding the link between CLD and CVD. The retrospective study analysed anonymous data from the SUMMIT study to assess the vascular function in patients with CLD in the presence of CVD and type 2 diabetes mellitus, and shows a significantly greater PWV; p-value = 0.015 and carotid intima-media thickness (CIMT) in the CLD patients; p-value = 0.001. The Mendelian randomisation study investigated potential genetic causal links between CLD and arterial stiffness, which shows a significant association; p-value = 0.021. The cross-section study and BRIDGE study utilised biomarkers to determine if there are shared pathways that contribute to the development and progression of CLD and CVD, and shows significant differences in PWV, and microvascular function; p-value = 0.001, blood biomarkers include adiponectin, VCAM-1, GDF-15, coagulation factor III, syndecan-1, and matrix metalloproteinase (MMP-10); p-value = 0.001. In conclusion, this study revealed a significant association between CLD and CVD. Therefore, monitoring CVD risk, including assessment of endothelial dysfunction and arterial stiffness, in patients with CLD might be helpful for risk stratification and for identifying future CVD pathologies and disease progression. This emphasises the need to identify and manage comorbid CLD and CVD to target new or existing therapeutic approaches to control systemic inflammation and improve overall lung and cardiovascular health.9 0Item Restricted Efficiency of Nitric Oxide and Peroxynitrite Release by Endothelial Nitric Oxide Synthase Variants - Implications for Cardiovascular Disease and Aging(Ohio University, 2024-05) Alsulami, Seham; Malinski, Tadeusz; Dewald, HowardThe cardiovascular system is mainly regulated by nitric oxide (NO). A reduction in its synthesis or bioavailability might underlie the impaired endothelium-dependent vasodilatation, which is observed in the blood vessels of individuals with cardiovascular disease (CVD). The dysfunction of endothelium, which is a main characteristic of vascular aging, has been associated with low NO production and high production of cytotoxic peroxynitrite (ONOO-). Thus, the ratio of NO to ONOO- is an indicator of endothelial dysfunction. Moreover, vascular NO is produced by an enzyme called (endothelial nitric oxide synthase (eNOS), and its gene exhibits high polymorphism. However, it is unclear whether polymorphisms or haplotypes in the eNOS gene affect the NO production, ONOO- production, and eNOS coupling, as well as how aging impacts these haplotypes. The influence of the eNOS haplotype (consisting of single nucleotide polymorphisms (SNP) in the promoter region (T-786C) and (C-665T) and exon 7 (Glu298Asp) and a variable number of tandem repeats (VNTR) in intron 4 (4a/4b/4c)) on the production of NO and ONOO- and eNOS coupling was investigated. Sanger sequencing and DNA electrophoresis were used to detect SNPs and VNTRs in the samples, respectively. To evaluate the production of NO and ONOO-, nanosensors were used to determine the maximal concentrations of NO and ONOO- and traditional and low-temperature SDS-PAGE to evaluate the expression of eNOS and the eNOS dimer/monomer ratio, respectively. Interestingly, these results indicated that the eNOS haplotype (H5) combining the “T T/C C 4b” of the G894T, T-786C, C-665T, and 27 bp VNTR a/b/c is more susceptible to endothelial dysfunction. Compared with other haplotype samples, it had lower [NO]/[ONOO-] and higher eNOS expression with reduced eNOS dimer/monomer (P < 0.005). These findings have important implications for understanding the genetic basis of cardiovascular disease and aging and may lead to new therapeutic approaches to these diseases.37 0Item Restricted Socioeconomic inequalities in cardiovascular diseases risk factors: Analysis of the Health Survey of England(Saudi Digital Library, 2023-11-01) Abideen, Raseel; Douiri, AbdelIntroduction: Cardiovascular diseases present a significant global health challenge, contributing substantially to morbidity and mortality. This complex issue arises from a confluence of genetic, lifestyle, and environmental factors. Despite medical advancements, socioeconomic determinants persist as formidable barriers to achieving equitable health outcomes. Addressing these inequalities is pivotal in mitigating the impact of cardiovascular diseases on public health. Aim: The primary aim of this research is to investigate the association between socioeconomic factors and the prevalence of three cardiovascular risk factors: hypertension, obesity, and smoking. By delving into the Health Survey of England dataset for 2019, this study seeks to unravel the complex web of associations that link demographic and socioeconomic strata with the prevalence of these risk factors. Methodology: This research adopts a cross-sectional design, leveraging the comprehensive Health Survey of England dataset. Analyzing a range of demographic and socioeconomic variables, the study employs rigorous statistical methods, including chi-square tests, logistic regression, and descriptive analysis. This approach offers a comprehensive examination of the relationships between socioeconomic factors and cardiovascular risk profiles. Results: The study offers nuanced insights into the interplay of age and hypertension, revealing a significant surge in prevalence and odds beyond the age of 45. Distinct ethnic disparities in hypertension prevalence highlights higher rates among Black individuals, signifying their increased susceptibility. Socioeconomic status emerges as an important factor, with lower income groups displaying elevated odds of hypertension. Exploring obesity patterns uncovers the influence of gender and culture, with males at higher risk and Asian ethnic groups displaying lower odds. Socioeconomic status is again noteworthy, as higher standing correlates with decreased obesity risk. Smoking behaviors exhibit age-related variation, with young adults aged 25-34 displaying the highest prevalence and likelihood of being current smokers. Ethnic disparities in smoking behaviors underscore cultural influences, while income and deprivation complexities link with smoking behaviors. Conclusion: This dissertation underscores the interconnected nature of age, gender, ethnicity and socioeconomic status in shaping cardiovascular risk profiles. Recommendations include targeted interventions for hypertension among older adults and ethnic minority populations, culturally sensitive obesity interventions, and comprehensive antismoking initiatives. Findings emphasize the significance of addressing health disparities and fostering equitable health outcomes in the pursuit of a healthier future for all.17 0