Saudi Cultural Missions Theses & Dissertations
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Item Restricted Diet related quailty of life of school-age children with type 1 diabetes mellitus(University of Leeds, 2024) Alharbi, Faten Fahad; Orfila, Caroline and Holmes MelvinManaging type 1 diabetes mellitus (T1DM) is challenging: blood glucose monitoring several times a day; total carbohydrate calculation to determine and adjust insulin requirements prior to mealtimes; insulin administration, either through multiple daily injections (MDI) or a pump; and diet modification. These necessary survival measures consume inordinate amounts of time and effort in the life of a person with diabetes. Ensuring that carbohydrate intake meets essential amounts also presents a major challenge. All of these requirements can have a serious impact on the quality of life (QoL) of school-age children. However, no recent studies have evaluated the impact of T1DM on the diet-related quality of life (D-QoL) of schoolchildren in the United Kingdom (UK). An additional deficiency is the limited availability of quantitative data, which might hinder the creation and acceptance of strategies for the development of improvements in this area. The overall aim of this research was therefore to employ quantitative measures as much as possible for an investigation of the impact of T1DM on the D-QoL of school-age children from their parents’ perspective, as well as to assess the children's intake of carbohydrate-rich foods. A newly designed two-part instrument was employed for these purposes: a D-QoL survey was adapted specifically for assessing the QoL of schoolchildren with T1DM, and a semi-quantitative food frequency questionnaire (SFFQ) was designed for evaluating the dietary intake of schoolchildren both with and without T1DM. In addition, thematic analysis was applied for the analysis of open-ended questions. A total of 181 schoolchildren (n = 42) with T1DM, and (n = 139) without T1DM aged 4 to 18 years old were included in this study. D-QoL scores were calculated based on averaged responses of each participant, with higher values indicating enhanced QoL. The results of the calculations seemed to indicate that most parents scored their children’s QoL in the medium category. Pearson’s correlation coefficient was applied for testing the relationships between a child’s age, duration of diabetes, HbA1c level, D-QoL scores, and total carbohydrate intake. No significant correlations were found between factors, with the exception of the age of schoolchildren with T1DM and their total carbohydrate intake, which was confirmed through a further linear regression: their total carbohydrate intake increased by 7.225 g for each year of their age. An independent sample t-test was used for comparing the differences in the average daily intake of total carbohydrates and sugar between school-age children with and without T1DM. The results showed that the average carbohydrate intake of schoolchildren with T1DM was 17.8% lower (-17.8%) than that of those without T1DM. The thematic analysis results revealed parents’ perceptions of a lack of T1DM related knowledge on the part of school staff. As well, the analysis demonstrated a dearth of carbohydrate information and portion sizes on school menus. Barriers to participation in social events such as parties, special occasions, and school activities involving food provided by others were another D-QoL-associated issue commonly cited by the families of children with T1DM. While broad generalization of the study results is limited by pandemic-related restrictions that affected sample size, the work reported here has broken new ground and serves to illuminate avenues for future research, which could benefit from input from children with T1DM, their parents, dietitians, healthcare professionals (HCPs), school staff, and catering providers. This research can guide future studies aimed at addressing T1DM-related issues in school settings, especially with regard to developing school menus that detail readily comprehensible carbohydrate content.12 0Item Restricted The impacts of commonly used medications on the trans-sulphuration pathway(The University of Nottingham, 2024-08-30) Alsaeedi, Asrar; Rose, PeterWorldwide life expectancy is predicted to increase, which can lead to an increased reliance on medications to manage multimorbidity. Self-medication and cost of living crisis has increased this pattern. The trend towards increased medication use can increase the possibility of having a larger population at risk of micronutrient deficiencies / inadequacy in users. Despite the widespread use of medications, studies on drug-nutrient interactions remain limited. This is particularly concerning for critical metabolic processes like the trans-sulphuration pathway (TSP) that depend on vitamin B6 for its flux. This work employed a multi-faceted approach aimed at providing crucial insights into how commonly prescribed drugs influence the TSP. We conducted a scoping review to assess current evidence on the impacts of medications on TSP metabolites in humans using paracetamol (APAP) as a model therapeutic. Eight out of 13 studies showed that, despite a lack of risk factors for dysregulate glutathione (GSH) homeostasis among participants in this review, significant reduction in GSH upon short-term use (≤ 4 days) of APAP treatment was reported. No definitive conclusion could be made regarding other TSP metabolites assessed due to lack of human studies. While we acknowledge these metabolic targets are largely identified as GSH related due to the known detoxification pathway for APAP. This review raised a gap of knowledge which would be interesting to investigate; i) advancing age coupled with malnutrition with low protein intakes and other specific dietary patterns with low SAAs (such as vegetarian) are reported in animal models as risk factors for APAP-induced GSH depletion leading to toxicity; whether or not this phenomena and other health consequences viz. sarcopenia would mirror such studies in humans needs further investigation, and ii) previous in vitro work showed that GSH depletion can lead to H2S production reduction, we hence raise a hypothesis that APAP-associated cardiovascular risk may be mediated through reduced H2S production resulting from GSH depletion. Secondary, reductions in dietary vitamin B6 and pyridoxal 5′-phosphate (PLP) levels could affect the flux of TSP and are associated with increased relative risk of age- related diseases. In regards to this, we carried out a secondary analysis using the National Diet and Nutrition Survey Rolling Programme (NDNS) to assess dietary intake of vitamin B6 and plasma PLP among the UK population (aged ≥ 19 years) and to investigate the impact of common medications on vitamin B6 status. Results showed that median dietary vitamin B6 intake of UK population met the reference nutrient intake (RNI) reaching 1.7 mg day-1 and the median plasma PLP in the entire population was 42.8 nmol L-1 and were higher than the threshold for vitamin B6 deficiency. However, data showed that both plasma PLP concentrations and dietary vitamin B6 intake tend to decline with age (P < 0.001). The NDNS data set included twelve reported therapeutic drugs. Of these, only antidepressant was associated with low dietary vitamin B6 (P = 0.007, R2 = 0.15). Seven drug classes were associated with plasma PLP concentrations reduction namely lipid-lowering drugs, analgesics, antibacterials, antidiabetics, antidepressants, Ca2+ blocker and prescribed asthma. Further, we validated and developed a human hepatoma HepG2 model to assess the cytotoxicity profile of two drugs, APAP and sulphasalazine (SSZ). Results showed that both APAP and SSZ exhibit cytotoxicity in HepG2 cells. Mechanistic findings showed possible mechanisms of cytotoxicity i) inducing early oxidative markers; ROS formation, lipid peroxidation and mitochondria depolarisation (P < 0.01, for both drugs) and ii) inducing later markers of apoptotic cascade; DNA damage, LDH leakage and PARP cleavage. Both drugs are partially caspase-dependent, however, caspase-3 plays a more prominent role in the apoptotic cascade induced by SSZ. Both drugs significantly reduce intracellular GSH levels in a concentration-dependent manner at 24 hours (P < 0.001, for both drugs). Interestingly, APAP at low concentrations (≤1 mM) significantly reduced cellular GSH levels without immediate cell death. However, this GSH depletion increased cell vulnerability to additional oxidative stress i.e. DNA damage. In the second set of our in vitro studies, we assessed the impact of APAP and SSZ on hydrogen sulphide (H2S) and it key enzymes (CBS and CSE), alongside polysulphide (H2Sn) levels. We showed that APAP could indirectly affect H2S production in HepG2 cells by significantly reduce the expressions of CBS (P < 0.01) and CSE (P = 0.023), however, no significant direct reduction in H2S was noticed upon short time APAP exposure (up to 4 hours). SSZ showed interesting findings as CSE expression was significantly elevated when cells were treated for 24 hours with low concentrations (0.12 mM and 0.25 mM; (P = 0.034, P = 0.049), respectively). At higher concentrations, CSE expression started to decrease, though not statistically significantly. A concentration-dependent reduction in CBS expression, however, not statistically significant, was noticed when cells treated with SSZ. In this chapter, we also assess the impact of H2S and H2Sn donors (NaHS and Na2S2, respectively) on APAP- and SSZ- induced oxidative stress markers. Our results showed both NaHS and Na2S2 had protection effects as shown by reduction in ROS formation, lipid peroxidation, mitochondria depolarisation, LDH leakage, DNA damage, cleaved PARP as well as preserving GSH levels. But also, both donors can act as direct scavengers as both NaHS and Na2S2 exhibit antioxidant properties, detected by the ABTS and copper reduction assays. In conclusion, multi-faceted investigation provides evidence for medication-induced dysregulation of the TSP metabolites, enzymes and vitamin B6 cofactor. However, further work is needed to measure TSP metabolites in humans using medications such as Tau and H2S and whether or not their reductions contributed to some side effects of drugs. A causal link between medication use, vitamin B6 inadequacy and changes in TSP metabolites in humans, an interesting area to be explored in the future.10 0Item Restricted Assessment of low-intake dehydration in hospitalised older people and the role of Bioelectrical Impedance Spectroscopy(University of Southampton, 2024-06-27) Alsanie, Saleh; Wootton, Stephen; Lim, Stephen; Ibrahim, KindaBackground: Older people are susceptible to low-intake dehydration, which is often not recognised and can result in significant morbidity through falls, constipation, delirium, respiratory and urinary tract disorders, and even death. Identifying low-intake dehydration at hospital admissions is challenging, leading to treatment delays and poor outcomes. Aims: To examine the factors underlying the identification of low-intake dehydration in older people admitted to Medicine for Older People (MOP) wards at University Hospital Southampton NHS Trust and to explore the feasibility of performing a study whereby bioelectrical impedance analysis (BIA) might be used alongside existing hydration risk screening tools in identifying low-intake dehydration in older people admitted to hospital. Methodology: A narrative review of the role of water in the body and the consequences of dehydration was carried out. This was followed by a sequential explanatory mixed-methods study involving quantitative service evaluation of recognition of dehydration in MOP wards and qualitative staff interviews to determine barriers and facilitators of hydration care and examine the factors influencing the routine assessment and diagnosis of dehydration in MOP wards. This led to a systematic review of the literature on the role of BIA in detecting low-intake dehydration. Finally, a study was conducted to examine the feasibility of conducting measurements of hydration status in hospitalised older patients using the existing hospital screening tool for dehydration and BIA measurements. Results: Most older patients admitted were at moderate to severe risk of developing dehydration. The service evaluation of hydration care provision showed good compliance with completing the initial hydration assessment. However, follow-up of patients at severe risk via 24-hour fluid balance charts needed improvement. Nursing and medical staff were aware of the importance of assessing hydration status but faced challenges in the diagnosis and management of dehydration. The proposed design for a study exploring the concurrent validity of the current screening tools and bedside measurements of BIA, its implementation and conduct was shown to be both feasible and acceptable to patients and staff and generated high-quality impedance measurements at the bedside alongside routine clinical care. Clinical demographics and directly measured impedance values of resistance, reactance, phase angle and impedance ratio were obtained in 25 patients reflected both age and hydration state but did not significantly correlate with risk categorisation of dehydration based on the established screening tools. Conclusion: Identifying older people admitted to hospitals who are at risk of or have low-intake dehydration requires continued vigilance, adherence to screening and assessment, and continued oversight within ordered systems and processes. Continued service improvement and staff training are needed, together with objective measures of hydration status, such as bioelectrical impedance, which may be used to improve clinical decision-making and care. Further studies are required to determine the reliability and validity of BIA in detecting low-intake dehydration compared with pre-existing objective measures such as serum osmolality, as well as its cost-effectiveness and evaluability in clinical practice.35 0Item Restricted Enhancing iron bioavailability from cereals as a strategy to reduce iron deficiency: in vitro digestion studies and a randomised control trial in UK females(Saudi Digital Library, 2023-12-24) Arafsha, Sarah Mohammed; Sharp, PaulBackground and hypothesis: Iron deficiency (ID) is the most common nutritional deficiency worldwide, and progress towards prevention of this disorder is slow. Plant foods are important sources of minerals in the United Kingdom. For example, 50% of iron is provided by cereals and a further 15% by vegetables. However, physical encapsulation within plant cells and the presence of absorption inhibitors such as phytic acid limit the availability of iron from plants for absorption in the human small intestine. The overall hypothesis for this project is physical disruption of wheat flour cell walls will increase the release of iron (i.e. the bioaccessibility) from foods during digestion and thereby enhance the bioavailability of iron from wheat-based foods. If successful, this change in milling of flour may provide a strategy to reduce the incidence of ID. Materials and methods: Studies were carried out using wheat flour produced by either standard milling or by micro-milling to reduce flour particle size. Mineral content of foods were determined by ICP-OES. The effects of cooking (boiling and baking), digestive enzymes, and pH on iron bioaccessibility from wheat-based foods following in vitro digestion was measured by ICP-OES. Food digests were applied to intestinal Caco-2 cells and iron bioavailability was assessed using ICP-MS. A human study was also carried out to assess the bioavailability of iron wheat breads made from standard and micronized flour. Results and conclusion: Micro-milling reduced flour particle size by 3-times. Foods made from micronized flour had higher iron bioavailability. This was particularly evident following gastric digestion when pH was low. In summary, the results suggest that micro-milling may increase iron bioaccessibility and bioavailability of iron from wheat flour. If endogenous iron in wheat-based foods was more bioavailable this might decrease the incidence of ID seen in some population groups in the UK.14 0Item Restricted Assessing metabolic profiling for personalised nutrition(Saudi Digital Library, 2023-09-27) Alqarni, Lina; Frost, GaryBackground: Non-communicable diseases (NCDs) are the main causes of mortality and morbidity, globally and in the UK. Dietary changes, such as increasing intake of fibre, fruits and vegetables and reducing intake of saturated fat, free sugar and salt, have shown positive impacts on the risk factors associated with NCDs. However, there are concerns about the effectiveness of general dietary advice, due to the ineffectiveness in motivating people to change their eating habits or differences in individual biological responses to dietary intakes. Personalised dietary advice is proposed as an effective approach when considering the differences in individual response to diet and can be a more proactive intervention when it comes to encouraging people to change their eating habits. Recent advances have been made in the development of a new methodology that uses metabolic profiling and multivariate mathematical modelling to provide objective, accurate information about an individual's dietary patterns based on urine composition, which can be used to design personalised nutritional interventions. The aim of the thesis is to assess the feasibility of translating the metabolic profiling strategy into clinic to improve the nutritional management in the prevention of NCDs, including cardiovascular disease (CVD), by objectively assessing dietary habits and monitoring the compliance to dietary recommendations in order to provide personalised nutritional advice. Methods: Data from a previous pilot study was used to investigate concordance between metabolic profiling and traditional methods on long term dietary assessment in order to assess accurate dietary intakes. In a highly controlled environment, a randomised inpatient crossover clinical trial was conducted to assess the impact of dietary interventions on urinary metabolic profiles and clinical parameters in order to build a new mathematical model, particularly for people at risk of CVD. A dietary protocol was developed to facilitate personalised dietary counselling in alignment with public and patient involvement. A randomised pilot clinical trial was conducted to assess the feasibility of providing metabolically personalised dietary advice in clinic to help people at risk of CVD to change their dietary habits within their own environment using the new mathematical model and dietary protocol. Results: Findings from the pilot study showed poor agreement between the DASH score and the urinary dietary patterns score in overall data and subgroups. There were discrepancies in the concordance between the classifications of the dietary adherence of the urinary biomarkers and their related dietary intakes. In the randomised inpatient trial, two distinct isoenergetic dietary interventions with different compliance levels to NICE dietary guidelines were designed. Significant differences in the dietary intakes between the interventions (Diet1 vs Diet2) were reflected in the urinary metabolic profiles of participants; the RM-MCCV-PLS-DA model shows clear separation in the global urinary metabolic profiles of the two dietary patterns. A robust model has been developed using the global urinary metabolic profile associated with distinct dietary patterns. A dietary protocol has been developed to facilitate personalised dietary counselling and this was in alignment with public and patient involvement (PPI). PPI has positively impacted our dietary intervention design, researchers, dietitians, and participants at risk of CVD who involved in PPI activities. Finally, the randomised pilot clinical trial shows the feasibility of using metabolic profiling in clinic to personalise dietary advice for people at risk of CVD. Conclusion: A metabolic profiling strategy is promising and feasible and can objectively provide information about dietary adherence. In addition, it can be applied in conjunction with traditional dietary assessment methods to obtain further details about individual diets. However, some considerations need to be taken when applying urinary metabolic profiles in personalise nutrition and further research is needed to enhance the application of urinary metabolic profile.13 0Item Restricted Association Between Diet Quality, Tooth Loss, and Dental Caries: Data from NHANES 2015-2018(Saudi Digital Library, 2023-04) Alghamdi, Sondos; AlDosari, Muath; Hayes, Catherine; Chamut, Steffany; Leung, CindyBackground: Optimum oral health and nutrition are essential to achieve and maintain overall and systemic health. The relationship between nutritional status and oral health has been examined in several studies. Cariogenic dietary patterns have been associated with tooth loss and dental caries. Dietary factors affect a variety of health factors, such as oral health, aside from social and psychological areas essential to maintaining the quality of life (QoL). This study aims to investigate the association between AHEI-2010, tooth loss and dental caries. Methods: Using the data from NHANES 2015-2018, we included adults 18 years and older. We measured the status of tooth loss, dental caries, and the diet quality of the individuals using AHEI-2010 and investigated the association between them while adjusting for covariates using Poisson and Logistic regression. Results: The mean AHEI-2010 score was 38.7±10.8 (out of 100). Our results showed an inverse association between the diet quality index (AHEI-2010) score and the presence of untreated coronal and root carious lesions and the loss of functional dentition. The mean ratio of teeth with untreated caries among the third quartile was 0.61 times the average number of teeth (95% CI=0.47, 0.78) and 0.49 times among individuals in the fourth quartile (95% CI=0.36, 0.66) compared to the lowest quartile group. Conclusion: This study indicates that lower diet quality measured using the AHEI- 2010 is associated with coronal and root dental caries and loss of functional dentition. Establishing a strong evidence-based foundation of the association between diet patterns and oral-systemic health can facilitate the development and promotion of sustainable, effective policies, strategies, and cost-effective interventions with the end goal of improving diet intake, oral-overall health, and food security while reducing the risk of developing malnutrition, diet-related NCDs, disability, and premature deaths.26 0