Displaying publications 1 - 20 of 34 in total

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  1. Fulltext Current state of the use of antibiotic prophylactics in cardiac surgery - correspondence
    Abdul-Rahman T, Omran MO, Ekerin O, Ghosh S, Awuah WA
    Int J Surg, 2023 Aug 01;109(8):2542-2543.
    PMID: 37158146 DOI: 10.1097/JS9.0000000000000445
  2. Antioxidant, anti-inflammatory and epigenetic potential of curcumin in Alzheimer's disease
    Abdul-Rahman T, Awuah WA, Mikhailova T, Kalmanovich J, Mehta A, Ng JC, et al.
    Biofactors, 2024 Jan 16.
    PMID: 38226733 DOI: 10.1002/biof.2039
    Alzheimer's disease (AD) constitutes a multifactorial neurodegenerative pathology characterized by cognitive deterioration, personality alterations, and behavioral shifts. The ongoing brain impairment process poses significant challenges for therapeutic interventions due to activating multiple neurotoxic pathways. Current pharmacological interventions have shown limited efficacy and are associated with significant side effects. Approaches focusing on the early interference with disease pathways, before activation of broad neurotoxic processes, could be promising to slow down symptomatic progression of the disease. Curcumin-an integral component of traditional medicine in numerous cultures worldwide-has garnered interest as a promising AD treatment. Current research indicates that curcumin may exhibit therapeutic potential in neurodegenerative pathologies, attributed to its potent anti-inflammatory and antioxidant properties. Additionally, curcumin and its derivatives have demonstrated an ability to modulate cellular pathways via epigenetic mechanisms. This article aims to raise awareness of the neuroprotective properties of curcuminoids that could provide therapeutic benefits in AD. The paper provides a comprehensive overview of the neuroprotective efficacy of curcumin against signaling pathways that could be involved in AD and summarizes recent evidence of the biological efficiency of curcumins in vivo.
  3. Letter: Addressing Neurosurgery Research and Data Access Gaps in War-Inflicted Nations
    Adebusoye FT, Awuah WA, Swaminathan N, Ghosh S, Wellington J, Abdul-Rahman T, et al.
    Neurosurgery, 2023 Aug 01;93(2):e30-e31.
    PMID: 37192472 DOI: 10.1227/neu.0000000000002527
  4. A study on the genetic polymorphisms of CYP3A5 among the Orang Asli in Malaysia using a next generation sequencing platform
    Ang GY, Yu CY, Johari James R, Ahmad A, Abdul Rahman T, Mohd Nor F, et al.
    Ann Hum Biol, 2018 Mar;45(2):166-169.
    PMID: 29447003 DOI: 10.1080/03014460.2018.1440004
    BACKGROUND: CYP3A5 is the predominant sub-family of biotransformation enzymes in the liver and the genetic variations in CYP3A5 are an important determinant of inter-individual and inter-ethnic differences in CYP3A-mediated drug disposition and response.

    AIM: This study aims to investigate the genetic polymorphisms of CYP3A5 among the Orang Asli in Peninsular Malaysia using a next generation sequencing platform.

    METHODS: Genomic DNAs were extracted from blood samples of the three main Orang Asli tribes and whole-genome sequencing was performed.

    RESULTS: A total of 61 single nucleotide polymorphisms were identified and all the SNPs were located in introns except rs15524, which is in the 3'UTR, and 11 of these polymorphisms were novel. Two allelic variants and three genotypes were identified in the Orang Asli. The major allelic variant was the non-functional CYP3A5*3 (66.4%). The percentages of Orang Asli with CYP3A5*3/*3 (47.2%) and CYP3A5*1/*3 (38.1%) genotypes are more than twice the percentage of Orang Asli with CYP3A5*1/*1 (14.8%) genotype. Almost half of the Orang Asli harboured CYP3A5 non-expressor genotype (CYP3A5*3/*3).

    CONCLUSIONS: The predominance of the CYP3A5 non-expressor genotype among the Orang Asli was unravelled and the findings in this study may serve as a guide for the optimisation of pharmacotherapy for the Orang Asli community.

  5. Fulltext Detection of CYP2C19 Genetic Variants in Malaysian Orang Asli from Massively Parallel Sequencing Data
    Ang GY, Yu CY, Subramaniam V, Abdul Khalid MI, Tuan Abdu Aziz TA, Johari James R, et al.
    PLoS One, 2016;11(10):e0164169.
    PMID: 27798644 DOI: 10.1371/journal.pone.0164169
    The human cytochrome P450 (CYP) is a superfamily of enzymes that have been a focus in research for decades due to their prominent role in drug metabolism. CYP2C is one of the major subfamilies which metabolize more than 10% of all clinically used drugs. In the context of CYP2C19, several key genetic variations that alter the enzyme's activity have been identified and catalogued in the CYP allele nomenclature database. In this study, we investigated the presence of well-established variants as well as novel polymorphisms in the CYP2C19 gene of 62 Orang Asli from the Peninsular Malaysia. A total of 449 genetic variants were detected including 70 novel polymorphisms; 417 SNPs were located in introns, 23 in upstream, 7 in exons, and 2 in downstream regions. Five alleles and seven genotypes were inferred based on the polymorphisms that were found. Null alleles that were observed include CYP2C19*3 (6.5%), *2 (5.7%) and *35 (2.4%) whereas allele with increased function *17 was detected at a frequency of 4.8%. The normal metabolizer genotype was the most predominant (66.1%), followed by intermediate metabolizer (19.4%), rapid metabolizer (9.7%) and poor metabolizer (4.8%) genotypes. Findings from this study provide further insights into the CYP2C19 genetic profile of the Orang Asli as previously unreported variant alleles were detected through the use of massively parallel sequencing technology platform. The systematic and comprehensive analysis of CYP2C19 will allow uncharacterized variants that are present in the Orang Asli to be included in the genotyping panel in the future.
  6. Multilevel Pharmacological Effects of Antipsychotics in Potential Glioblastoma Treatment
    Awuah WA, Kalmanovich J, Mehta A, Huang H, Abdul-Rahman T, Cheng Ng J, et al.
    Curr Top Med Chem, 2023;23(5):389-402.
    PMID: 36593538 DOI: 10.2174/1568026623666230102095836
    Glioblastoma Multiforme (GBM) is a debilitating type of brain cancer with a high mortality rate. Despite current treatment options such as surgery, radiotherapy, and the use of temozolomide and bevacizumab, it is considered incurable. Various methods, such as drug repositioning, have been used to increase the number of available treatments. Drug repositioning is the use of FDA-approved drugs to treat other diseases. This is possible because the drugs used for this purpose have polypharmacological effects. This means that these medications can bind to multiple targets, resulting in multiple mechanisms of action. Antipsychotics are one type of drug used to treat GBM. Antipsychotics are a broad class of drugs that can be further subdivided into typical and atypical classes. Typical antipsychotics include chlorpromazine, trifluoperazine, and pimozide. This class of antipsychotics was developed early on and primarily works on dopamine D2 receptors, though it can also work on others. Olanzapine and Quetiapine are examples of atypical antipsychotics, a category that was created later. These medications have a high affinity for serotonin receptors such as 5- HT2, but they can also act on dopamine and H1 receptors. Antipsychotic medications, in the case of GBM, also have other effects that can affect multiple pathways due to their polypharmacological effects. These include NF-B suppression, cyclin deregulation, and -catenin phosphorylation, among others. This review will delve deeper into the polypharmacological, the multiple effects of antipsychotics in the treatment of GBM, and an outlook for the field's future progression.
  7. In Reply: The State of Cerebrovascular Care in Africa
    Awuah WA, Tenkorang PO, Ng JC, Abdul-Rahman T
    Neurosurgery, 2023 Jul 01;93(1):e16.
    PMID: 37097024 DOI: 10.1227/neu.0000000000002515
  8. The unmet need of organ transplantation in Africa
    Awuah WA, Ng JC, Bulut HI, Nazir A, Tenkorang PO, Yarlagadda R, et al.
    Int J Surg, 2023 Mar 01;109(3):519-520.
    PMID: 36927835 DOI: 10.1097/JS9.0000000000000025
  9. Ailing neurosurgical services in rural Africa
    Awuah WA, Adebusoye FT, Tenkorang PO, Mehta A, Mustapha MJ, Debrah AF, et al.
    Int J Surg, 2023 Mar 01;109(3):227-229.
    PMID: 36906787 DOI: 10.1097/JS9.0000000000000020
  10. The African cancer burden: what is the potential role of modern oncology innovation in reducing the continent's rapidly rising mortality?
    Awuah WA, Ng JC, Mehta A, Nansubuga EP, Abdul-Rahman T, Kundu M, et al.
    Postgrad Med J, 2023 Aug 22;99(1175):941-945.
    PMID: 37280156 DOI: 10.1093/postmj/qgad043
    With increasing prevalence and an expected rise in disease burden, cancer is a cause of concern for African healthcare. The cancer burden in Africa is expected to rise to 2.1 million new cases per year and 1.4 million deaths annually by the year 2040. Even though efforts are being made to improve the standard of oncology service delivery in Africa, the current state of cancer care is not yet on par with the rise in the cancer burden. Cutting-edge technologies and innovations are being developed across the globe to augment the battle against cancer; however, many of them are beyond the reach of African countries. Modern oncology innovations targeted to ward Africa would be promising to address the high cancer mortality rates. The innovations should be cost-effective and widely accessible to tackle the rapidly rising mortality rate on the African continent. Though it may seem promising, a multidisciplinary approach is required to overcome the challenges associated with the development and implementation of modern oncology innovations in Africa.
  11. Fulltext Circadian rhythm in systemic autoimmune conditions: Potential of chrono-immunology in clinical practice: A narrative review
    Awuah WA, Huang H, Kalmanovich J, Mehta A, Mikhailova T, Ng JC, et al.
    Medicine (Baltimore), 2023 Aug 11;102(32):e34614.
    PMID: 37565922 DOI: 10.1097/MD.0000000000034614
    The circadian rhythm (CR) is a fundamental biological process regulated by the Earth's rotation and solar cycles. It plays a critical role in various bodily functions, and its dysregulation can have systemic effects. These effects impact metabolism, redox homeostasis, cell cycle regulation, gut microbiota, cognition, and immune response. Immune mediators, cycle proteins, and hormones exhibit circadian oscillations, supporting optimal immune function and defence against pathogens. Sleep deprivation and disruptions challenge the regulatory mechanisms, making immune responses vulnerable. Altered CR pathways have been implicated in diseases such as diabetes, neurological conditions, and systemic autoimmune diseases (SADs). SADs involve abnormal immune responses to self-antigens, with genetic and environmental factors disrupting self-tolerance and contributing to conditions like Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Inflammatory Myositis. Dysregulated CR may lead to increased production of pro-inflammatory cytokines, contributing to the systemic responses observed in SADs. Sleep disturbances significantly impact the quality of life of patients with SADs; however, they are often overlooked. The relationship between sleep and autoimmune conditions, whether causal or consequential to CR dysregulation, remains unclear. Chrono-immunology investigates the role of CR in immunity, offering potential for targeted therapies in autoimmune conditions. This paper provides an overview of the connections between sleep and autoimmune conditions, highlighting the importance of recognizing sleep disturbances in SADs and the need for further research into the complex relationship between the CR and autoimmune diseases.
  12. Fulltext Postoperative mortality in Africa: are there any improvements in the last decade?
    Awuah WA, Ng JC, Nazir A, Tenkorang PO, Yarlagadda R, Kalmanovich J, et al.
    Int J Surg, 2023 May 01;109(5):1080-1082.
    PMID: 36927691 DOI: 10.1097/JS9.0000000000000125
  13. The molecular landscape of neurological disorders: insights from single-cell RNA sequencing in neurology and neurosurgery
    Awuah WA, Ahluwalia A, Ghosh S, Roy S, Tan JK, Adebusoye FT, et al.
    Eur J Med Res, 2023 Nov 16;28(1):529.
    PMID: 37974227 DOI: 10.1186/s40001-023-01504-w
    Single-cell ribonucleic acid sequencing (scRNA-seq) has emerged as a transformative technology in neurological and neurosurgical research, revolutionising our comprehension of complex neurological disorders. In brain tumours, scRNA-seq has provided valuable insights into cancer heterogeneity, the tumour microenvironment, treatment resistance, and invasion patterns. It has also elucidated the brain tri-lineage cancer hierarchy and addressed limitations of current models. Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis have been molecularly subtyped, dysregulated pathways have been identified, and potential therapeutic targets have been revealed using scRNA-seq. In epilepsy, scRNA-seq has explored the cellular and molecular heterogeneity underlying the condition, uncovering unique glial subpopulations and dysregulation of the immune system. ScRNA-seq has characterised distinct cellular constituents and responses to spinal cord injury in spinal cord diseases, as well as provided molecular signatures of various cell types and identified interactions involved in vascular remodelling. Furthermore, scRNA-seq has shed light on the molecular complexities of cerebrovascular diseases, such as stroke, providing insights into specific genes, cell-specific expression patterns, and potential therapeutic interventions. This review highlights the potential of scRNA-seq in guiding precision medicine approaches, identifying clinical biomarkers, and facilitating therapeutic discovery. However, challenges related to data analysis, standardisation, sample acquisition, scalability, and cost-effectiveness need to be addressed. Despite these challenges, scRNA-seq has the potential to transform clinical practice in neurological and neurosurgical research by providing personalised insights and improving patient outcomes.
  14. 3D printing in surgery: revolutionizing trauma and fracture care in low and middle-income countries
    Awuah WA, Tenkorang PO, Adebusoye FT, Ng JC, Wellington J, Abdul-Rahman T, et al.
    Postgrad Med J, 2023 Dec 21;100(1179):1-3.
    PMID: 37857514 DOI: 10.1093/postmj/qgad100
  15. Fulltext Exploring the current landscape of single-cell RNA sequencing applications in gastric cancer research
    Awuah WA, Roy S, Tan JK, Adebusoye FT, Qiang Z, Ferreira T, et al.
    J Cell Mol Med, 2024 Apr;28(7):e18159.
    PMID: 38494861 DOI: 10.1111/jcmm.18159
    Gastric cancer (GC) represents a major global health burden and is responsible for a significant number of cancer-related fatalities. Its complex nature, characterized by heterogeneity and aggressive behaviour, poses considerable challenges for effective diagnosis and treatment. Single-cell RNA sequencing (scRNA-seq) has emerged as an important technique, offering unprecedented precision and depth in gene expression profiling at the cellular level. By facilitating the identification of distinct cell populations, rare cells and dynamic transcriptional changes within GC, scRNA-seq has yielded valuable insights into tumour progression and potential therapeutic targets. Moreover, this technology has significantly improved our comprehension of the tumour microenvironment (TME) and its intricate interplay with immune cells, thereby opening avenues for targeted therapeutic strategies. Nonetheless, certain obstacles, including tumour heterogeneity and technical limitations, persist in the field. Current endeavours are dedicated to refining protocols and computational tools to surmount these challenges. In this narrative review, we explore the significance of scRNA-seq in GC, emphasizing its advantages, challenges and potential applications in unravelling tumour heterogeneity and identifying promising therapeutic targets. Additionally, we discuss recent developments, ongoing efforts to overcome these challenges, and future prospects. Although further enhancements are required, scRNA-seq has already provided valuable insights into GC and holds promise for advancing biomedical research and clinical practice.
  16. Fulltext Recent Outcomes and Challenges of Artificial Intelligence, Machine Learning, and Deep Learning in Neurosurgery
    Awuah WA, Adebusoye FT, Wellington J, David L, Salam A, Weng Yee AL, et al.
    World Neurosurg X, 2024 Jul;23:100301.
    PMID: 38577317 DOI: 10.1016/j.wnsx.2024.100301
    Neurosurgeons receive extensive technical training, which equips them with the knowledge and skills to specialise in various fields and manage the massive amounts of information and decision-making required throughout the various stages of neurosurgery, including preoperative, intraoperative, and postoperative care and recovery. Over the past few years, artificial intelligence (AI) has become more useful in neurosurgery. AI has the potential to improve patient outcomes by augmenting the capabilities of neurosurgeons and ultimately improving diagnostic and prognostic outcomes as well as decision-making during surgical procedures. By incorporating AI into both interventional and non-interventional therapies, neurosurgeons may provide the best care for their patients. AI, machine learning (ML), and deep learning (DL) have made significant progress in the field of neurosurgery. These cutting-edge methods have enhanced patient outcomes, reduced complications, and improved surgical planning.
  17. Fulltext Natural selection and local adaptation of blood pressure regulation and their perspectives on precision medicine in hypertension
    Hoh BP, Abdul Rahman T, Yusoff K
    Hereditas, 2019;156:1.
    PMID: 30636949 DOI: 10.1186/s41065-019-0080-1
    Prevalence of hypertension (HTN) varies substantially across different populations. HTN is not only common - affecting at least one third of the world's adult population - but is also the most important driver for cardiovascular diseases. Yet up to a third of hypertensive patients are resistant to therapy, contributed by secondary hypertension but more commonly the hitherto inability to precisely predict response to specific antihypertensive agents. Population and individual genomics information could be useful in guiding the selection and predicting the response to treatment - an approach known as precision medicine. However this cannot be achieved without the knowledge of genetic variations that influence blood pressure (BP). A number of evolutionary factors including population demographics and forces of natural selection may be involved. This article explores some ideas on how natural selection influences BP regulation in ethnically and geographically diverse populations that could lead to them being susceptible to HTN. We explore how such evolutionary factors could impact the implementation of precision medicine in HTN. Finally, in order to ensure the success of precision medicine in HTN, we call for more initiatives to understand the genetic architecture within and between diverse populations with ancestry from different parts of the world, and to precisely classify the intermediate phenotypes of HTN.
  18. NeuroVerse: neurosurgery in the era of Metaverse and other technological breakthroughs
    Kundu M, Ng JC, Awuah WA, Huang H, Yarlagadda R, Mehta A, et al.
    Postgrad Med J, 2023 May 22;99(1170):240-243.
    PMID: 36892407 DOI: 10.1093/postmj/qgad002
    The tremendous evolution in modern technology has led to a paradigm shift in neurosurgery. The latest advancements such as augmented reality, virtual reality, and mobile applications have been incorporated into neurosurgical practice. NeuroVerse, representing the application of the metaverse in neurosurgery, brings enormous potential to neurology and neurosurgery. Implementation of NeuroVerse could potentially elevate neurosurgical and interventional procedures, enhance medical visits and patient care, and reshape neurosurgical training. However, it is also vital to consider the challenges that may be associated with its implementation, such as privacy issues, cybersecurity breaches, ethical concerns, and widening of existing healthcare inequalities. NeuroVerse adds phenomenal dimensions to the neurosurgical environment for patients, doctors, and trainees, and represents an incomparable advancement in the delivery of medicine. Therefore, more research is needed to encourage widespread use of the metaverse in healthcare, particularly focusing on the areas of morality and credibility. Although the metaverse is expected to expand rapidly during and after the COVID-19 pandemic, it remains to be seen whether it represents an emerging technology that will revolutionize our society and healthcare or simply an immature condition of the future.
  19. Erratum to: Differential positive selection of malaria resistance genes in three indigenous populations of Peninsular Malaysia
    Liu X, Yunus Y, Lu D, Aghakhanian F, Saw WY, Deng L, et al.
    Hum Genet, 2015 Jun;134(6):677.
    PMID: 25783005 DOI: 10.1007/s00439-015-1540-y
  20. Embracing robotic surgery in low- and middle-income countries: Potential benefits, challenges, and scope in the future
    Mehta A, Cheng Ng J, Andrew Awuah W, Huang H, Kalmanovich J, Agrawal A, et al.
    Ann Med Surg (Lond), 2022 Dec;84:104803.
    PMID: 36582867 DOI: 10.1016/j.amsu.2022.104803
    Robotic surgery has applications in many medical specialties, including urology, general surgery, and surgical oncology. In the context of a widespread resource and personnel shortage in Low- and Middle-Income Countries (LMICs), the use of robotics in surgery may help to reduce physician burnout, surgical site infections, and hospital stays. However, a lack of haptic feedback and potential socioeconomic factors such as high implementation costs and a lack of trained personnel may limit its accessibility and application. Specific improvements focused on improved financial and technical support to LMICs can help improve access and have the potential to transform the surgical experience for both surgeons and patients in LMICs. This review focuses on the evolution of robotic surgery, with an emphasis on challenges and recommendations to facilitate wider implementation and improved patient outcomes.
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