Saudi Cultural Missions Theses & Dissertations
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Item Restricted Objective and Subjective Long-Term Cognitive Outcomes in COVID-19 Survivors Managed with ECMO: A Case Series(Royal Holloway, University of London, 2024) Alanazi, Abeer; Crabtree, AnnaCOVID-19 has been associated with significant health complications, including cognitive impairments, particularly among patients requiring intensive care interventions. A subset of these patients, especially those needing extracorporeal membrane oxygenation (ECMO), face heightened vulnerability due to prolonged Intensive Care Unit (ICU) stay and extended ECMO duration, placing them at an increased risk of developing post intensive care syndrome (PICS), a multifaceted condition that affects cognitive and psychological functions among other health- related domains. This study aims to investigate the cognitive screening outcomes and characteristics of cognitive impairments among COVID-19 survivors managed with ECMO, enhancing our understanding of cognitive outcomes in this high-risk group. Eighty-five COVID-19 patients who had been treated with ECMO were contacted after their ICU admission. The Telephone Montreal Cognitive Assessment (T-MoCA) was employed to detect cognitive impairment. Neuropsychological assessment was completed with ten survivors. A case series design was employed to characterise the cognitive profile of these ten COVID-19 survivors. The mean T-MoCA score for the 49 cohort was 16.20 (SD = 2.93), indicating cognitive impairment among COVID-19 survivors managed with ECMO. T-MoCA scores for the ten patients who completed neuropsychological assessments ranged from 10 to 19, with a mean score of 16.2 (SD = 2.94). The case series analysis demonstrated impairments across domains of attention, working memory, processing speed, and memory. Cognitive impairments are evident in COVID-19 survivors managed with ECMO, presenting cognitive profiles similar to those documented in acute respiratory distress syndrome (ARDS) patients (non-COVID-19). Key words: ICU, COVID-19, ECMO, Cognitive Impairment, PICS12 0Item Restricted Structural basis for the roles of single and double Holliday Junctions formed from Human telomeric Nucleic Acids (HJTNA)(Univeristy College London, 2024-04-28) Alanazi, Abeer; Shozeb, HaiderBackground: Telomeres, nucleoprotein complexes at chromosome ends, are crucial for genomic stability. Cancer cells maintain telomere length via telomerase or alternative lengthening of telomeres (ALT). The ALT pathway, observed in 15% of cancers, involves recombination and employs Holliday junction intermediates. These 4-way DNA motifs are dynamic structures influenced by cations, particularly Magnesium (Mg²⁺), leading to conformational changes. Aims: This study aims to explore Holliday junction stability and mobility in the context of ALT, focusing on the impact of G-rich sequences. Leveraging single-molecule Förster resonance energy transfer (smFRET) and X-ray crystallography, we aim to understand the influence of varying Mg²⁺ ion concentrations on the Holliday junctions. Additionally, we investigate protein-Holliday junction complexes and assess the role of Mg²⁺ ions in proteinDNA binding affinity. Methodology: smFRET and X-ray crystallography have been employed to study Holliday junction structures. Microscale thermophoresis (MST) quantified protein-DNA binding affinity at different Mg²⁺ ion concentrations. T4 endonuclease VII, T7 endonuclease I, and the WRWYRGGRYWRW peptide were tested for their affinity under varying Mg²⁺ conditions. Results and Conclusions: The results highlight the direct influence of Mg²⁺ ions on Holliday junction stability. Protein-DNA binding affinity was observed through MST, with T4 endonuclease VII, T7 endonuclease I, and the WRWYRGGRYWRW peptide exhibiting persistent affinity at lower Mg²⁺ concentrations. However, affinity diminished at higher concentrations. smFRET analysis provided insights into branch migration rates across diverse Mg²⁺ ion conditions, suggesting a potential strategy for targeting ALT-positive cancer cells by stabilizing Holliday junction conformation. This study offers valuable insights into the ALT mechanism.13 0