The Impact of COVID-19 on the Health-Related Behaviours, Mental Well-Being, and Academic Engagement of a Cohort of Undergraduate Students in an Irish University Setting.

Given the well-established impact of COVID-19 on university students' health and lifestyle parameters, the current study sought to investigate these impacts within an Irish university setting. A cross-sectional design was employed, with a 68-item questionnaire instrument disseminated to all Year 2 undergraduate students in the host institution (N = 2752), yielding a 9.7% response rate (n = 266). This questionnaire elicited students' self-reported changes to health-related behaviours, mental well-being and academic engagement across 4 defined time-points: (T0: prior to COVID-19, T1: initial onset of COVID-19, T2: during COVID-19, and T3: time of data collection). Many items were adapted from previous Irish research and additional validated scales included the Alcohol Use Disorders Identification Test (AUDIT-C) and the World Health Organisation's Well-being scale (WHO-5). Key findings revealed that at T1, substantially more males reported 'good/very good' general health than females (76.3% vs. 70.8%), while physical activity patterns followed a similar trend at both T0 (80% vs. 66.1%) and T1 (66.7% vs. 61%). A total of 78.4% of participants reported a body mass gain from T0 to T3, thus reflecting the reduced physical activity levels and compromised nutritional patterns across this period. Worryingly, AUDIT-C scale data revealed hazardous drinking habits were evident in both males and females, while fruit and vegetable intake, physical activity levels, and mental well-being among this cohort remained notably sub-optimal. Ratings of positive academic engagement also decreased substantially between T0 (90.3%) and T3 (30.4%). These findings substantiate the rationale for tailored health promotion interventions in university settings to support students' transition back to traditional programme delivery and, of equal importance, to improve general health and well-being post-COVID-19 within this cohort.

Inhibitory Properties of Aldehydes and Related Compounds against Phytophthora infestans-Identification of a New Lead.

The pathogen Phytophthora infestans is responsible for catastrophic crop damage on a global scale which totals billions of euros annually. The discovery of new inhibitors of this organism is of paramount agricultural importance and of critical relevance to food security. Current strategies for crop treatment are inadequate with the emergence of resistant strains and problematic toxicity. Natural products such as cinnamaldehyde have been reported to have fungicidal properties and are the seed for many new discovery research programmes. We report a probe of the cinnamaldehyde framework to investigate the aldehyde subunit and its role in a subset of aromatic aldehydes in order to identify new lead compounds to act against P. infestans. An ellipticine derivative which incorporates an aldehyde (9-formyl-6-methyl ellipticine, 34) has been identified with exceptional activity versus P. infestans with limited toxicity and potential for use as a fungicide.

Synthesis and Evaluation of Novel Ellipticines and Derivatives as Inhibitors of Phytophthora infestans.

The pathogen Phytophthora infestans is responsible for worldwide catastrophic crop damage and discovery of new inhibitors of this organism is of paramount agricultural and industrial importance. Current strategies for crop treatment are inadequate with limitations of efficacy and market alternatives. Ellipticines have recently been reported to have fungicidal properties and have been assessed against P. infestans growth with promising results. We hereby report a probe of the ellipticine framework to investigate the alkyl subunit and screen a set ellipticines and derivatives to identify new lead compounds to act against P. infestans. A series of ellipticinium salt derivatives have been identified with exceptional growth inhibitory activity and apparent lack of toxicity towards a human cell-line surpassing the effect of known and marketed fungicides. This report identifies the potential of this natural product derivative as a novel fungicide.

Novel 11-Substituted Ellipticines as Potent Anticancer Agents with Divergent Activity against Cancer Cells.

Ellipticines have well documented anticancer activity, in particular with substitution at the 1-, 2-, 6- and 9-positions. However, due to limitations in synthesis and coherent screening methodology the full SAR profile of this anticancer class has not yet been achieved. In order to address this shortfall, we have set out to explore the anticancer activity of this potent natural product by substitution. We currently describe the synthesis of novel 11-substituted ellipticines with two specific derivatives showing potency and diverging cellular growth effects.

7-formyl-10-methylisoellipticine, a novel ellipticine derivative, induces mitochondrial reactive oxygen species (ROS) and shows anti-leukaemic activity in mice.

Acute myeloid leukaemia (AML) is the most common type of leukaemia in adults and is associated with high relapse rates. Current treatment options have made significant progress but the 5 year survival for AML remains low and therefore, there is an urgent need to develop novel therapeutics. Ellipticines, a class of cancer chemotherapeutic agents, have had limited success clinically due to low solubility and toxic side effects. Isoellipticines, novel isomers of ellipticine, have been designed to overcome these limitations. One particular isoellipticine, 7-formyl-10-methylisoellipticine, has previously showed strong ability to inhibit the growth of leukaemia cell lines. In this study the anti-leukaemia effect of this compound was investigated in detail on an AML cell line, MV4-11. Over a period of 24 h 7-formyl-10-methyl isoellipticine at a concentration of 5 µM can kill up to 40 % of MV4-11 cells. Our research suggests that the cytotoxicity of 7-formyl-10-methylisoellipticine is partially mediated by an induction of mitochondrial reactive oxygen species (ROS). Furthermore, 7-formyl-10-methylisoellipticine demonstrated promising anti-tumour activity in an AML xenograft mouse model without causing toxicity, implying the potential of isoellipticines as novel chemotherapeutic agents in the treatment of leukaemia.

Community-dwelling women's knowledge of urinary incontinence.

As the population ages, the risk and prevalence of urinary incontinence (UI) will increase. Although this is the case, many women do not seek help or treatment. It is therefore important to investigate women's knowledge of UI. This pilot study aimed to describe community-dwelling women's knowledge of UI. A convenience sample method was used to recruit 50 community-dwelling women aged 50 and over. Some 36 participants completed a demographic questionnaire and the Urinary Incontinence Knowledge Scale (UIKS)-a response rate of 72%. The findings indicated that participants had poor knowledge of UI, principally in relation to risk, prevention, treatment and management factors. Fewer than 20% of participants indicated they had been given information on bladder and bowel health issues. The findings suggested that women had unmet educational needs relating to UI. Community nurses have a key role to play in promoting targeted awareness and continence education advice regarding UI to community-dwelling women.

Synthesis and evaluation of novel ellipticines as potential anti-cancer agents.

Drugs that inhibit DNA topoisomerase I and DNA topoisomerase II have been widely used in cancer chemotherapy. We report herein the results of a focused medicinal chemistry effort around novel ellipticinium salts which target topoisomerase I and II enzymes with improved solubility. The salts were prepared by reaction of ellipticine with the required alkyl halide and evaluated for DNA intercalation, topoisomerase inhibition and growth inhibition against 12 cancer cell lines. Results from the topoisomerase I relaxation assay indicated that all novel ellipticine derivatives behaved as intercalating agents. At a concentration of 100 µM, specific topoisomerase I inhibition was not observed. Two of the derivatives under investigation were found to fully inhibit the DNA decatenation reaction at a concentration of 100 µM, indicative of topoisomerase II inhibition. N-Alkylation of ellipticine was found to enhance the observed growth inhibition across all cell lines and induce growth inhibition comparable to that of Irinotecan (CPT-11; GI(50) 1-18 µM) and in some cell lines better than Etoposide (VP-16; GI(50) = 0.04-5.2 µM). 6-Methylellipticine was the most potent growth inhibitory compound assessed (GI(50) = 0.47-0.9 µM). N-Alkylation of 6-methylellipticine was found to reduce this response with GI(50) values in the range of 1.3-28 µM.

Synthesis and biological evaluation of novel isoellipticine derivatives and salts.

Synthesis of novel 7-substituted isoellipticines and isoellipticinium salts is described, with optimisation of routes, representing a new class of anti-cancer agent. Initial assessment of biological activity using a topoisomerase II decatenation assay and NCI screening highlighted strong anti-cancer activity, further developed in a panel of isoellipticinium salts. Interestingly, low correlation between results of the topoisomerase II decatenation assay and NCI screen throughout the panel suggest that topo II is not the most important biological target with respect to anti-cancer activity in this new class of compounds. Results also suggest that solubility is not the limiting factor in activity of the isoellipticinium salts. Overall, 20 novel ellipticine analogues were prepared and full anti-cancer profiling was completed for 13 isoellipticine derivatives and salts. Two compounds display significant specificity towards CNS cancer cell lines and are lead compounds for future development.

E4BP4 expression is regulated by the t(17;19)-associated oncoprotein E2A-HLF in pro-B cells.

The E4BP4 basic leucine zipper (bZIP) transcription factor is regulated by interleukin-3 (IL-3) in pro-B cells and has been reported to promote survival of the murine IL-3-dependent pro-B cell lines, FL5.12 and Baf-3. The E2A-HLF oncoprotein arises from a t(17;19) translocation in childhood pro-B cell acute lymphoblastic leukaemia and acts as an anti-apoptotic factor in FL5.12 and Baf-3 cells. To assess the functions of E2A-HLF and E4BP4 in cell survival, a tetracycline-inducible system was established in Baf-3 cells to express E4BP4 or E2A-HLF. Upon IL-3 withdrawal, expression of E2A-HLF conferred resistance to apoptosis whereas overexpression of E4BP4 did not. E4BP4 and E2A-HLF both recognized the same DNA sequence in reporter gene assays, but had opposite effects on transcription. E2A-HLF acts as a transcriptional activator and E4BP4 as a transcriptional repressor. Furthermore, E4BP4 is a downstream transcriptional target of E2A-HLF. Our data suggests that the overexpression of E4BP4 is unable to block apoptosis induced by IL-3 withdrawal and that the expression of E2A-HLF does not replace the function of E4BP4 in mediating survival.