https://www.um.edu.mt/library/oar/handle/123456789/16100 Sat, 31 Oct 2026 21:23:48 GMT 2026-10-31T21:23:48Z https://www.um.edu.mt/library/oar/handle/123456789/150627 Title: Alpha/beta-gamma decoupling in methylphenidate medicated ADHD patients Authors: Zammit, Nowell; Muscat, Richard Abstract: There is much interest to understand how different neural rhythms function, interact and are regulated. Here, we focus on WM delay gamma to investigate its coupling with alpha/beta rhythms and its neuromodulation by methylphenidate. We address this through the use of human EEG conducted in healthy and ADHD subjects which revealed ADHD-specific electrophysiological deficits and MPHinduced normalization of gamma amplitude and its coupling with alpha/beta rhythms. Decreased alpha/beta-gamma coupling is known to facilitate memory representations via disinhibition of gamma ensembles coding the maintained stimuli. Here, we present EEG evidence which suggests that these dynamics are sensitive to catecholaminergic neuromodulation. MPH decreased alpha/betagamma coupling and this was related to the increase in delay-relevant gamma activity evoked by the same drug. These results add further to the neuromodulatory findings that reflect an electrophysiological dimension to the well-known link between WM delay and catecholaminergic transmission. Sun, 01 Jan 2023 00:00:00 GMT https://www.um.edu.mt/library/oar/handle/123456789/150627 2023-01-01T00:00:00Z https://www.um.edu.mt/library/oar/handle/123456789/149885 Title: Glioblastoma multiforme : molecular biology and updated systematic review on natural extract and phytochemical efficacy in-vitro Authors: Cuschieri, Andrea; Baron, Byron Abstract: Glioblastoma multiforme (GBM) is the most prevalent primary malignant central nervous system tumours (CNST). Current treatment consists of surgical resection and adjuvant chemoradiotherapy, the gold-standard agent being Temozolomide (TMZ). Despite optimal treatment, GBM has an abysmal associated prognosis of approximately 15 months. The disproportionately high morbidity and mortality necessitate studies which strive to increase knowledge on putative therapeutic agents to confirm or deny their possible use against GBM Therefore, there is an urgent need to develop a deep understanding of GBM molecular biology upon which more effective therapeutic strategies may be developed.; Natural extracts and phytochemicals have shown promise as potential therapeutic agents against GBM. In this review, the molecular biology of GBM and molecular factors which contribute to therapeutic resistance are discussed in depth. The mechanisms by which phytochemicals and natural extracts exhibit can inhibit GBM growth and proliferation are discussed. Moreover, statistical analysis demonstrated that natural extracts and phytochemicals may be superior to TMZ in-vitro. This review demonstrates that phytochemicals have great potential as novel therapeutic agents against GBM. Further preclinical and clinical studies are needed to determine the optimal doses, routes of administration, and potential toxicities of these agents, but their unique molecular targets and low toxicity profiles make them attractive candidates for further investigation. Sun, 01 Jan 2023 00:00:00 GMT https://www.um.edu.mt/library/oar/handle/123456789/149885 2023-01-01T00:00:00Z https://www.um.edu.mt/library/oar/handle/123456789/146213 Title: A practical checklist for return of results from genomic research in the European context Authors: Vears, Danya F.; Hallowell, Nina; Bentzen, Heidi Beate; Ellul, Bridget; Nøst, Therese Haugdahl; Kerasidou, Angeliki; Kerr, Shona M.; Mayrhofer, Michaela Th.; Mežinska, Signe; Ormondroyd, Elizabeth; Solberg, Berge; Sand, Birgitte Wirum; Budin-Ljøsne, Isabelle Abstract: An increasing number of European research projects return, or plan to return, individual genomic research results (IRR) to participants. While data access is a data subject’s right under the General Data Protection Regulation (GDPR), and many legal and ethical guidelines allow or require participants to receive personal data generated in research, the practice of returning results is not straightforward and raises several practical and ethical issues. Existing guidelines focusing on return of IRR are mostly projectspecific, only discuss which results to return, or were developed outside Europe. To address this gap, we analysed existing normative documents identified online using inductive content analysis. We used this analysis to develop a checklist of steps to assist European researchers considering whether to return IRR to participants. We then sought feedback on the checklist from an interdisciplinary panel of European experts (clinicians, clinical researchers, population-based researchers, biobank managers, ethicists, lawyers and policy makers) to refine the checklist. The checklist outlines seven major components researchers should consider when determining whether, and how, to return results to adult research participants: 1) Decide which results to return; 2) Develop a plan for return of results; 3) Obtain participant informed consent; 4) Collect and analyse data; 5) Confirm results; 6) Disclose research results; 7) Follow-up and monitor. Our checklist provides a clear outline of the steps European researchers can follow to develop ethical and sustainable result return pathways within their own research projects. Further legal analysis is required to ensure this checklist complies with relevant domestic laws. Sun, 01 Jan 2023 00:00:00 GMT https://www.um.edu.mt/library/oar/handle/123456789/146213 2023-01-01T00:00:00Z https://www.um.edu.mt/library/oar/handle/123456789/139139 Title: 5-Fluorouracil dose escalation generated desensitized colorectal cancer cells with reduced expression of protein methyltransferases and no epithelial-to-mesenchymal transition potential Authors: Fenech, Kimberly; Micallef, Isaac; Baron, Byron Abstract: Background: Colorectal cancer (CRC) is one of the most frequently diagnosed cancers. In many cases, the poor prognosis of advanced CRC is associated with resistance to treatment with chemotherapeutic drugs such as 5-Fluorouracil (5-FU). The epithelial-to-mesenchymal transition (EMT) and dysregulation in protein methylation are two mechanisms associated with chemoresistance in many cancers. This study looked into the effect of 5-FU dose escalation on EMT and protein methylation in CRC.; Materials and Methods: HCT-116, Caco-2, and DLD-1 CRC cell lines were exposed to dose escalation treatment of 5-FU. The motility and invasive potentials of the cells before and after treatment with 5-FU were investigated through wound healing and invasion assays. This was followed by a Western blot which analyzed the protein expressions of the epithelial marker E-cadherin, mesenchymal marker vimentin, and the EMT transcription factor (EMT-TF), the snail family transcriptional repressor 1 (Snail) in the parental and desensitized cells. Western blotting was also conducted to study the protein expressions of the protein methyltransferases (PMTs), Euchromatic histone lysine methyltransferase 2 (EHMT2/G9A), protein arginine methyltransferase (PRMT5), and SET domain containing 7/9 (SETD7/9) along with the global lysine and arginine methylation profiles.; Results: The dose escalation method generated 5-FU desensitized CRC cells with distinct morphological features and increased tolerance to high doses of 5-FU. The 5-FU desensitized cells experienced a decrease in migration and invasion when compared to the parental cells. This was reflected in the observed reduction in E-cadherin, vimentin, and Snail in the desensitized cell lines. Additionally, the protein expressions of EHMT2/G9A, PRMT5, and SETD7/9 also decreased in the desensitized cells and global protein lysine and arginine methylation became dysregulated with 5-FU treatment.; Conclusion: This study showed that continuous, dose-escalation treatment of 5-FU in CRC cells generated 5-FU desensitized cancer cells that seemed to be less aggressive than parental cells. Mon, 01 Jan 2024 00:00:00 GMT https://www.um.edu.mt/library/oar/handle/123456789/139139 2024-01-01T00:00:00Z