Browsing by Author "Atiomo, William"
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Publication Coenzyme A Restriction as a Factor Underlying Pre-Eclampsia with Polycystic Ovary Syndrome as a Risk Factor(2022) Atiomo, WilliamAbstract: Pre-eclampsia is the most common pregnancy complication affecting 1 in 20 pregnancies, characterized by high blood pressure and signs of organ damage, most often to the liver and kidneys. Metabolic network analysis of published lipidomic data points to a shortage of Coenzyme A (CoA). Gene expression profile data reveal alterations to many areas of metabolism and, crucially, to conflicting cellular regulatory mechanisms arising from the overproduction of signalling lipids driven by CoA limitation. Adverse feedback loops appear, forming sphingosine-1-phosphate (a cause of hypertension, hypoxia and inflammation), cytotoxic isoketovaleric acid (inducing acidosis and organ damage) and a thrombogenic lysophosphatidyl serine. These also induce mitochondrial and oxidative stress, leading to untimely apoptosis, which is possibly the cause of CoA restriction. This work provides a molecular basis for the signs of pre-eclampsia, why polycystic ovary syndrome is a risk factor and what might be done to treat and reduce the risk of disease.Publication Deciphering the Role of Insulin-Like Growth Factor 1 in Endometrial Cancer in Patients With Polycystic Ovary Syndrome: Protocol for a Methodological Approach Using Cell Culture Experiments(2023) Atiomo, William; Alqutami, Fatma; Albasha, Sara; Hachim, MahmoodBackground: Endometrial cancer (EC) is the most common gynecological cancer in women globally. It is linked to increasing obesity rates and longer life spans. The molecular mechanisms leading to EC are unclear; however, women with polycystic ovary syndrome (PCOS) have a 3- to 5-fold increased EC risk. According to a pilot study conducted in the United Kingdom, insulin-like growth factor-1 (IGF-1) gene and protein were raised in the endometrium and blood of women with EC and PCOS, compared with those without PCOS (controls). Therefore, raised serum IGF-1 levels may contribute to an increased EC risk in women with PCOS, but it is necessary to test this hypothesis since not all studies have demonstrated this association. Objective: This study aims to investigate the role of IGF-1 in mediating EC risk in PCOS. This will be achieved by evaluating the proliferative effects of PCOS serum, IGF-1, and IGF-1 antagonist on human endometrial cancer 1-A and 1-B cell lines, with a comparison to controls (using serum from women without PCOS and cell culture media). The study will also identify differentially expressed genes and pathways activated by various treatments. Methods: We intend to recruit 20 women with PCOS and 20 women without PCOS for this cross-sectional study. All experiments will be carried out 4 times to ensure consistency. We will perform transcriptomic and phosphoproteomic profiling to identify differentially expressed genes and phosphoproteins between different treatments using RNA sequencing and phosphoproteomics. We will also perform bioinformatics pathway analysis to identify whether any unique collection of genes or phosphoproteins explains increased EC risk in PCOS. The primary outcome measure will be the cell proliferation (growth) difference measured by cell index values. Our protocol stands out due to its unique approach; no previous study has used this approach to investigate the oncogenic effect of serum from women with PCOS. Additionally, no previous study has considered the differential mutations of genes related to the insulin signaling pathway across various types of human EC cell lines and the potential impact of these variations on their experimental findings. Results: Participants are currently being recruited. It is expected that preliminary findings suitable for analysis and publication will be available by the summer of 2024. Conclusions: Although we currently do not have any results to report, sharing our protocol at this stage will aid in research collaboration, provide an opportunity for early feedback, and help reduce duplication of effort by other research groups. The findings of our study will have broader implications. A deeper understanding of the mechanisms underlying the regulation of the IGF system in PCOS and EC will improve our ability to develop effective treatment modalities for EC and will be a vital step toward reducing EC in women globally.Publication Obesity and female infertility(2023) Ennab, Farah; Atiomo, WilliamAbstract: Infertility is a significant global health issue, with a negative impact on people's wellbeing and human rights. Despite the longstanding association between obesity and infertility, there remains uncertainty, about the precise mechanisms underpinning this association and best management strategies. In this article, we aimed to address these uncertainties by reviewing the recent literature, and focusing on studies which evaluated live birth rates. We found that just over half of the studies, investigating the relationship between preconception maternal weight and live birth rates found an inverse correlation. There was, however, insufficient evidence, that preconception maternal lifestyle or pharmacological interventions in obese women with infertility, resulted in improved live birth rates. The implications for clinical practice and future research are highlighted. For example, the need to consider some flexibility in applying strict preconception body mass index targets, limiting access to fertility treatment, and a need for large clinical trials of new pharmacological options and bariatric surgery.Publication Polycystic Ovarian Syndrome (PCOS): Does the Challenge End at Conception?(2022) Mirza, Fadi G.; Ennab, Farah; Hassan Khamis, Amar; Atiomo, WilliamAbstract: Polycystic ovary syndrome (PCOS) is a prevalent condition that not only has the potential to impede conception but also represents the most common endocrine dysfunction in fertile women. It is considered a heterogeneous and multifaceted disorder, with multiple reproductive and metabolic phenotypes which differently affect the early- and long-term syndrome’s risks. Undoubtedly, the impact of PCOS on infertility has attracted most of the attention of healthcare providers and investigators. However, there is growing evidence that even after conception is achieved, PCOS predisposes the parturient to several adverse pregnancy outcomes including a high risk of pregnancy-induced hypertension, spontaneous abortion, gestational diabetes, preeclampsia, and preterm birth, which increase the risks of stillbirth and neonatal death. Fetal growth abnormalities may also be more common, but the relationship is less well defined. This narrative review aims to summarize current knowledge regarding these conditions as they interplay with PCOS and concludes that although there appears to be an increase in these complications during the pregnancy of women with PCOS, there is a need for further research to clarify the possible confounding impact of obesity. Implications for clinical practice and future research are outlined.Publication Polycystic Ovary Syndrome and Endometrial Cancer: A Scoping Review of the Literature on Gut Microbiota(2022) Prakash, Amog; Nourianpour, Milad; Senok, Abiola; Atiomo, WilliamAbstract: Gut dysbiosis has been associated with polycystic ovary syndrome (PCOS) and endometrial cancer (EC) but no studies have investigated whether gut dysbiosis may explain the increased endometrial cancer risk in polycystic ovary syndrome. The aim of this scoping review is to evaluate the extent and nature of published studies on the gut microbiota in polycystic ovary syndrome and endometrial cancer and attempt to find any similarities between the composition of the microbiota. We searched for publications ranging from the years 2016 to 2022, due to the completion date of the ‘Human Microbiome Project’ in 2016. We obtained 200 articles by inputting keywords such as ‘gut microbiome’, ‘gut microbiota’, ‘gut dysbiosis’, ‘PCOS’, and ‘endometrial cancer’ into search engines such as PubMed and Scopus. Of the 200 identified in our initial search, we included 25 articles in our final review after applying the exclusion and inclusion criteria. Although the literature is growing in this field, we did not identify enough published studies to investigate whether gut dysbiosis may explain the increased EC risk in PCOS. Within the studies identified, we were unable to identify any consistent patterns of the microbiome similarly present in studies on women with PCOS compared with women with EC. Although we found that the phylum Firmicutes was similarly decreased in women with PCOS and studies on women with EC, there was however significant variability within the studies identified making it highly likely that this may have arisen by chance. Further research pertaining to molecular and microbiological mechanisms in relation to the gut microbiome is needed to elucidate a greater understanding of its contribution to the pathophysiology of endometrial cancer in patients with polycystic ovarian syndrome.Publication Prevalence of Polycystic Ovary Syndrome amongst Females Aged between 15 and 45 Years at a Major Women’s Hospital in Dubai, United Arab Emirates(2023) Mirza, Fadi G.; Tahlak, Muna A.; Hassan Khamis, Amar; Atiomo, WilliamAbstract: Objective criteria have been scarce in published data on the occurrence of polycystic ovary syndrome (PCOS) in the United Arab Emirates (UAE). It is crucial that we enhance our comprehension of PCOS prevalence in the UAE to inform key stakeholders about the disease’s burden and enable comparisons with other nations. This research aimed to examine the PCOS prevalence at a large academic tertiary centre in Dubai, UAE, called Latifa Women and Children’s Hospital. We performed a crosssectional study by reviewing the electronic medical records of patients accessing care between 2017 and 2022 (5 years). By utilizing the international classification of diseases codes (ICD-10), we discovered a period prevalence of PCOS of 1.6% among 64,722 women aged between 15 and 45 years. It is worth noting that the estimated annual point prevalence rose from 1.19% in 2020 (at the beginning of the COVID19 pandemic) to 2.72% in 2022 (after the start of the COVID-19 pandemic). Therefore, the odds ratio of the risk of a PCOS diagnosis in 2022 compared to 2020 was 2.28. The majority of the women diagnosed with PCOS in this study had an ICD-10 code of E28.2. Women with PCOS were younger than the controls, less likely to be pregnant, and had a higher body mass index and systolic and diastolic blood pressure. This is the most extensive research to date examining PCOS prevalence in the UAE, and it emphasizes the significance of this condition. It is crucial to prioritize PCOS to prevent morbidity and mortality from reproductive and long-term health consequences, including infertility, type 2 diabetes and endometrial cancer, which is presently the most frequent gynecological cancer in the UAE.Publication Prevalence of pre-eclampsia in women in the Middle East: a scoping review(2024-08) Hegazy, Ayatullah; Eid, Farida Abdelrehim; Ennab, Farah; Atiomo, William; Azar, Aida JosephAbstract Hypertensive disorders of pregnancy are the second most common cause of maternal deaths worldwide. Metabolic syndrome is recognized as one of the risk factors for pre-eclampsia. A recent study revealed a high prevalence of metabolic syndrome in the United Arab Emirates (UAE), particularly amongst Emirati women compared with global estimates. This finding raises the possibility that the prevalence of pre-eclampsia in the region may also be higher as research is increasingly demonstrating an association between pre-eclampsia and metabolic syndrome. We therefore conducted this scoping review of the literature to investigate the nature and extent of studies evaluating the prevalence of pre-eclampsia within the Middle East region to enable subsequent comparison of these findings with the global burden of pre-eclampsia, objectively identify gaps in the literature and inform the design of future studies to address these gaps. PubMed and Scopus were used to extract studies published over the last 20 years (2003-2023). The search terms used included ("Pre-eclampsia" AND "Prevalence") OR ("Hypertension in pregnancy" AND "Prevalence") OR ("Pregnancy" AND "Pre-eclampsia") OR ("Pre-eclampsia" AND "Epidemiology"). We limited our studies to those from the Middle East (ME). A total of 556 relevant articles were identified following which 11 were shortlisted for review. There were four studies from Iran, two from Saudi Arabia, two from Qatar, one from Jordan, and one from Bahrain. The remaining study included 29 countries from Africa, Asia, Latin America, and the Middle East of which data from Jordan, Lebanon, the Occupied Palestinian Territory, and Qatar were included. There were four retrospective, two cross-sectional, and two cohort studies, one prospective study, one meta-analysis, and one descriptive-analytical study. The prevalence of pre-eclampsia in the studies ranged from 0.17 to 5%. We did not find any study investigating the prevalence of pre-eclampsia in the United Arab Emirates. Based on our findings, we conclude that there is a significant scarcity of research in this area, especially within the Middle East, and notably an absence of studies specifically pertaining to the UAE. Consequently, we assert that there is a pressing requirement for additional research to evaluate the prevalence of pre-eclampsia in the region.Publication A scoping review of the literature on the impact of the COVID-19 quarantine on the psychological wellbeing of medical students(2022) Prakash, Amog; Nourianpour, Milad; Atiomo, WilliamBackground: The goal of this study was to identify the nature and extent of the available published research on the impact of social isolation, on the psychological wellbeing of medical students, who had to quarantine due to the COVID-19 pandemic. Methods: Design. Scoping review. Search strategy: The PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews), guideline, was used to structure this study. A search strategy was carried out across six bibliographic databases. PubMed, Embase, ERIC, Scopus, Cochrane Database of Systematic Reviews and Web of Science. The following search terms were used, "medical student*" AND "impact" AND "quarantine" AND "COVID-19". Searches were initially confined to articles published (excluding conference abstracts) between 1 January 2019- 21 August 2021 but updated in September 2022 with the original search terms expanded to include "isolation" or "lockdown" as well as "quarantine" and the period of search extended to 21 August 2022. A search of secondary references was conducted. Data from the selected studies were extracted, and the following variables recorded; first author and year of publication, country of study, study design, sample size, participants, mode of analysing impact of quarantine from COVID-19 on mental health and results of the studies. Results: A total of 223 articles were identified in the original search in 2021 and 387 articles, in the updated search in 2022. Following the exclusion of duplicates and application of the agreed inclusion and exclusion criteria, 31 full-text articles were identified for the final review, most of which were cross sectional studies. Sample sizes ranged from 13 to 4193 students and most studies used a variety of self-administered questionnaires to measure psychological wellbeing. Overall, 26 of the 31 articles showed that quarantine had a negative impact on the psychological well-being of medical students. However, two studies showed no impact, and three studies showed an improvement. Conclusion: The evidence is growing. Quarantine because of the COVID-19 pandemic may have had a negative impact on the psychological wellbeing of medical students, but this is not certain. There is therefore a need for more studies to further evaluate this research question.Publication Transcriptomic analysis identifies four novel receptors potentially linking endometrial cancer with polycystic ovary syndrome and generates a transcriptomic atlas(2023) Alqutami, Fatma; Hachim, Mahmood; Atiomo, WilliamAbstract: Polycystic Ovary Syndrome (PCOS) is associated with a 3 to 4-fold increased risk of endometrial cancer (EC), but molecular mechanisms are unclear. Upregulation of the IGF1 gene in PCOS endometrium may increase EC risk, but this is uncertain. We aimed to investigate links between EC and PCOS, by analysing publicly available transcriptomic data. The NCBI Gene Expression Omnibus was used to identify relevant studies. Differentially expressed genes (DEGs) were identified and analysed using Metascape to identify pathways of interest. PCOS DEGs that encode proteins secreted into blood were identified using the Human Protein Atlas blood protein database. EC DEGs that are cellular receptors were identified using EcoTyper. These were intersected to identify which EC receptors interact with PCOS secreted proteins. Seven receptors were identified in EC but only PTPRF, ITGA2, ITGA3 and ITGB4 genes were expressed on epithelial cells. Pathway enrichment of these genes showed that the major and common pathway involved was that of the PI3K-AKT signalling pathway which was consistent with a link between PCOS and EC. However, IGF1 was down regulated in PCOS and EC. These findings hold significant promise for improving our understanding of mechanistic pathways leading to EC in PCOS.Publication Vibrational Biospectroscopy: An Alternative Approach to Endometrial Cancer Diagnosis and Screening(2022) Atiomo, WilliamAbstract: Endometrial cancer (EC) is the sixth most common cancer and the fourth leading cause of death among women worldwide. Early detection and treatment are associated with a favourable prognosis and reduction in mortality. Unlike other common cancers, however, screening strategies lack the required sensitivity, specificity and accuracy to be successfully implemented in clinical practice and current diagnostic approaches are invasive, costly and time consuming. Such limitations highlight the unmet need to develop diagnostic and screening alternatives for EC, which should be accurate, rapid, minimally invasive and cost-effective. Vibrational spectroscopic techniques, MidInfrared Absorption Spectroscopy and Raman, exploit the atomic vibrational absorption induced by interaction of light and a biological sample, to generate a unique spectral response: a “biochemical fingerprint”. These are non-destructive techniques and, combined with multivariate statistical analysis, have been shown over the last decade to provide discrimination between cancerous and healthy samples, demonstrating a promising role in both cancer screening and diagnosis. The aim of this review is to collate available evidence, in order to provide insight into the present status of the application of vibrational biospectroscopy in endometrial cancer diagnosis and screening, and to assess future prospects.