Browsing by Author "Almutairi, Majed"

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AMIGO3 gene expression and function during oligodendrocyte differentiation in the central nervous system
(University of Birmingham, 2024-04-21) Almutairi, Majed; Fulton, Daniel; Ahmed, Zubair
Demyelination causes disruption to neuronal signalling and occurs in many neurodegenerative diseases or in response to brain injury. There are no cures available for demyelinating diseases, including multiple sclerosis (MS), the most common autoimmune inflammatory disease in the central nervous system (CNS). Current approaches to treat MS focus on anti-inflammatory drugs, which prevent demyelination progression and reduce clinical relapses, but do not allow repair or replacement myelin. A natural repair process called remyelination can occur following demyelination. Remyelination can help to repair demyelinating plaques and protect axons from degeneration, but endogenous remyelination is inefficient and fails with ageing and disease progression, Improving remyelination is therefore an important for the focus for the development of MS therapies. Studies of animal models have to led to the discovery of new therapeutic targets which can promote endogenous remyelination. An example is the leucine rich repeat protein (LRRP) leucine rich repeat and immunoglobulin-like domain containing protein 1 (LINGO1). Inhibition of LINGO1 promoted remyelination in several animal models of demyelination, but clinical inhabitation of LINGO1 showed unsuccessful results in clinical trials. We considered the idea that the LINGO1 clinical trials failed due to compensation from another LRRP, amphoterin-induced gene and open reading fram-3 (AMIGO3). AMIGO3 is upregulated more rapidly than LINGO1 after spinal cord injury (SCI) in animal models, and also increases in expression rapidly after axotomy in culture of dorsal root ganglion neurons and retinal ganglion cells. Importantly, AMIGO3 expression is rapidly increased in the CNS during postnatal development when myelinating oligodendrocyte (OL) are generated, and decreases again quickly after myelination begins. AMIGO3 may therefore act a regulator of OL differentiation, and its inhibition could be an alternative therapeutic target for demyelinating diseases. Considering the above, the first aim of this project was to study the function of AMIGO3 using in vitro models of OL differentiation. For this work, a primary mixed glial culture system was developed to study OL differentiation during early stage of CNS development. Using this system we found that AMIGO3 is downregulated in mixed glial cultures during OL differentiation. We also found that downregulation of AMIGO3 expression by siRNA resulted in the upregulation of OL maturation. On the other hand, increased AMIGO3 levels produced by treatment with recombinant AMIGO3 reduced OL maturation, and activated RhoA GTP activity, a molecule involved in AMIGO3 intracellular signalling. These findings suggest that AMIGO3 downregulates OL differentiation via RhoA GTP signalling. AMIGO3 is known to engage in homotypic interactions, thus expression on different glial cells could allow cell to cell signalling. Also, AMIGO3 is expressed in cells of the OL lineage and astrocytes, thus AMIGO3 expression in non-OL glia could provide a signal to regulate OL differentiation. Considering this idea, the second aim in this thesis was to compare the expression of AMIGO3 and LINGO1 in primary cultures of astrocytes and microglia. Using Western blot and immunocytochemistry we found strong expression of AMIGO3 proteins in astrocytes, but not in microglia. Surprisingly, we also found that astrocytes express LINGO1 proteins. This work shows that astrocytes, but not microglia, are an abundant source of both AMIGO3 and LINGO1, which together could influence OL differentiation and myelin formation and repair.
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Physiological and Biochemical Differences between Diabetes Type 1 and Diabetes Type 2
(University of New England, 2017-10-20) Almutairi, Majed; Farlane, Jim
The expression "diabetes" is gotten from the ancient Greek word 'diabainen', which means ‘go through’, to show the too much passage of urine from the kidney. Until the 1600s it was not included, nonetheless, that Willis included the expression "mellitus" ('sweet') to recognize this condition from an unreasonable production of non-sweet urine (diabetes 'insipidus')(Poretsky, 2010). Just about 200 years after the fact (1776), Dobson showed that sweet taste of urine wasbecause of an abundance of sugar in blood and urine. Another 100 more years were needed to demonstrate the pathogenesis of diabetes mellitus. In 1889, von Mering and Minkowski showed that pancreatectomised dogs created manifestations of diabetes, thus first time connecting diabetes surprisingly to a particular organ. In 1910, Sharpey-Schafer recommended that diabetic peoples were inadequate in a substance created in the pancreatic islets (found in 1869 by Langerhans) and called it 'insulin'; in this manner, a connection between the pancreas, insulin and diabetes was begun to develop and thus modern period of diabetes study started. It was just in 1921, in any case, that a more exact picture developed: Banting, Macleod and Best demonstrated that diabetes in pancreatectomised dogs could be turned around after the intravenous organization of the "islet" extracted from typical canine ancreata. Then, Best, Banting and Collip refined this substance from bovinepancreata, and the first patient was effectively treated in 1922, bringing about a decrease in blood glucose as well as glycosuria. In 1926, MacLean recommended a difference between 'hepatic glycosuria' and 'genuine diabetes'. After ten years, Himsworth, compressing his past research, recognized 'insulin-dependent' and 'insulin-independent' diabetes mellitus, with the last more treacherous condition portrayed by less serious hyperglycaemia. In the 1950s, a solid estimation of circling insulin with a radioimmunoassay system permitted a reasonable difference between 'insulin-dependent' and 'insulin-independent' diabetes mellitus, and the worldview of two pathophysiologically distinct disordersturned out to be increasingly clear in the folowing years (Zaccardi, Webb, Yates, & Davies, 2016).
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Satisfaction, Utilisation and Willingness to Pay for Primary Care Dental Services
(Queen’s University Belfast, 2024-07-02) Almutairi, Majed; O’Neill, Ciaran; McKenna, Gerry
It is a common objective to strive for better health. Keeping one's teeth healthy and practising appropriate oral hygiene are essential but frequently overlooked aspects. Poor dental health can have a detrimental effect on speech, diet, and general well-being and has been related to a range of serious health conditions. Nevertheless, there are substantial obstacles to receiving prompt, reasonably priced dental care. User preferences can offer insights into the publics’ perceptions of dental services' how they are valued and used. Potential disparities in oral health and the effectiveness of the healthcare system can also be found by analysing preferences differently among social groups. This emphasises how crucial oral health equity is to enable everyone to reach the highest standards regardless of social or economic background. This thesis aims to examine satisfaction, utilisation, and Willingness to Pay for dental care, to identify the underlying factors that lead to differences across these among various groups of individuals, and to assess how the context in which care is delivered affects them. The thesis consists of a number of studies, that use primary and secondary data from Saudi Arabia and the United Kingdom. It seeks to understand the perception of dental services, how these vary and what lessons might be learnt from this with respect to policy. The thesis is laid out in five chapters. In Chapter 1, the background to the study is provided and motivation for the subsequent empirical chapters set out. In Chapter 2 an empirical study that examine satisfaction with dental services are presented using the Donabedian framework to relate care quality to satisfaction. In this study, data from the British Social Attitudes Survey (BSAS) is used to examine the differences in satisfaction across different demographic groups and to track the development of this satisfaction over time. The chapter demonstrates using data from the UK, how satisfaction with dental services can vary within a publicly funded system throughout an economic cycle as the opportunities for private practice change and with it, access to dental care among publicly funded patients. Importantly the chapter underscores the challenges in analysing and interpreting the results of satisfaction survey data. In Chapter 3, the focus shifts to the utilisation of dental care, using the Andersen model as a conceptual framework. The chapter has been divided into two main sections. The first section emphasises the significance of accurately describing the concept of 'need' when examining variations in dental care use. Using data from the Scottish Health Survey, it highlights distinctions between those who use services for prevention and those who use services for treatment attention terms of their socio-demographics. The following section examines differences between regions in use of services that might be concealed by national statistics. The second study demonstrates the existence in Saudi Arabia of distinct patterns across regions in use of care related to socio-demographic characteristics of users. In Chapter 4, satisfaction with, utilisation of, and willingness to pay for dental care services in Saudi Arabia are examined using primary data analysis that collected face to face and online. the first study examines satisfaction with dental care in Saudi Arabia by conducting a comparative analysis of in-person and online surveys. This study highlights the possible influence of survey administration techniques on research findings. This study shows how overall satisfaction varies as satisfaction with specific aspects of service but not others vary, demonstrating that amenities and communication are critical drivers of overall satisfaction. In the second empirical study the utilisation of services as reported in face-to-face surveys and online surveys in Saudi Arabia are examined on the potential for sample selection is explored using data gathered during the COVID pandemic and its aftermath. In the third study, the utility theory used to examine the willingness of individuals in Saudi Arabia to pay for dental check-ups using online survey responses in Saudi Arabia. This study presents as a proof of principle a study of WTP in Saudi Arabia and amines differences in willingness to pay among various demographic groups. The validity of the study's estimated willingness-to-pay is validated internally and externally. It also examines the more general implications of these findings for fairness and healthcare policy, providing a thorough assessment of the financial elements of dental service accessibility and cost in Saudi Arabia. In the final chapter the lessons from across the various empirical studies are discussed, strengths and limitations of the work examined and areas for further research identified.
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