• A role for tumor necrosis factor-alpha in ischemia and ischemic preconditioning

      Watters, Orla; O'Connor, John J (2011-08-02)
      Abstract During cerebral ischemia, elevation of TNF-α and glutamate to pathophysiological levels may induce dysregulation of normal synaptic processes, leading ultimately to cell death. Previous studies have shown that patients subjected to a mild transient ischemic attack within a critical time window prior to a more severe ischemic episode may show attenuation in the clinical severity of the stroke and result in a more positive functional outcome. Studies with organotypic hippocampal cultures and mixed primary hippocampal cultures have shown that prior incubation with low concentrations of glutamate and TNF-α increase the resistance of neurones to a subsequent insult from glutamate, AMPA and NMDA, while co-exposure of TNF-α and for example AMPA may have neuroprotective effects compared to cultures exposed to excitotoxic agents alone. In addition our work has shown that although glutamate and TNF-α pretreatment induces analogous levels of desensitisation of the intracellular calcium dynamics of neurons under resting conditions and in response to acute glutamate stimulation, their downstream signalling pathways involved in this response do not converge. Glutamate and TNF-α would appear to have opposing effects on resting Ca2+ levels which supports the proposal that they have distinct modes of preconditioning.
    • An exploration of knowledge, attitudes and advice given by health professionals to parents in Ireland about the introduction of solid foods. A pilot study

      Allcutt, Claire; Sweeney, Mary-Rose (2010-04-21)
      Abstract Background For the purposes of this paper "weaning is defined as the introduction of the first solid foods to infants". Global recommendations by the World Health Organisation (WHO) recommend that all infants be exclusively breast-fed for the first six months of life. No global recommendations have been made for formula fed infants. In Europe it is recommended that weaning foods should be introduced between 18 weeks and 26 weeks regardless of whether infants are breast or formula fed. In the United Kingdom it is recommended that solids be introduced at around six-months for both breast and formula fed infants. In Ireland official guidelines recommend that breast fed infants should be introduced solids at 6 months of age while for formula fed infants the recommendation is for 4 months. The disparity between these global, European, UK and local recommendations may be a source of confusion for parents and health care professional based in Ireland. Emerging evidence suggests that babies in Ireland are given solid foods before the recommended age but there has been little investigation of the weaning advice provided by health professionals. Since community health professionals have routine parent interactions in the pre-weaning and early-weaning period and hence are in a unique position to positively influence parental weaning decisions, this study aimed to explore their knowledge, attitudes and advice practices about weaning. Methods A mixed-methods approach was used for the research, commencing with a multi-disciplinary focus group to guide and develop a questionnaire. Questionnaires were then distributed in a postal survey to General Practitioners (GPs) (n 179), Practice Nurses (PNs) (n 121), Public Health Nurses (PHNs) (n 107) and Community Dieticians (CDs) (n 8). Results The results indicate varying levels of knowledge of official weaning recommendations and a variety of advice practices. CDs and PHNs acknowledged a clear role in providing weaning advice while demonstrating high confidence levels in providing this advice. However, 19% of PNs and 7% of GP respondents did not acknowledge that they have a role in providing weaning advice to parents; even though Health Service Executive (HSE) written literature given to parents states that they should seek information from PNs and GPs. Conclusion Small pockets of misinformation about the introduction of solid foods persist amongst health professionals which may lead to inconsistent advice for parents. Further research is needed.
    • Analysis of pulsed cisplatin signalling dynamics identifies effectors of resistance in lung adenocarcinoma.

      Hastings, Jordan F; Gonzalez Rajal, Alvaro; Latham, Sharissa L; Han, Jeremy Zr; McCloy, Rachael A; O'Donnell, Yolande Ei; Phimmachanh, Monica; Murphy, Alexander D; Nagrial, Adnan; Daneshvar, Dariush; et al. (2020-06-09)
      The identification of clinically viable strategies for overcoming resistance to platinum chemotherapy in lung adenocarcinoma has previously been hampered by inappropriately tailored in vitro assays of drug response. Therefore, using a pulse model that closely mimics the in vivo pharmacokinetics of platinum therapy, we profiled cisplatin-induced signalling, DNA-damage and apoptotic responses across a panel of human lung adenocarcinoma cell lines. By coupling this data to real-time, single-cell imaging of cell cycle and apoptosis we provide a fine-grained stratification of response, where a P70S6K-mediated signalling axis promotes resistance on a TP53 wildtype or null background, but not a mutant TP53 background. This finding highlights the value of in vitro models that match the physiological pharmacokinetics of drug exposure. Furthermore, it also demonstrates the importance of a mechanistic understanding of the interplay between somatic mutations and the signalling networks that govern drug response for the implementation of any consistently effective, patient-specific therapy.
    • Assessing the Impact of COVID-19 Public Health Stages on Paediatric Emergency Attendance.

      McDonnell, Thérèse; Nicholson, Emma; Conlon, Ciara; Barrett, Michael; Cummins, Fergal; Hensey, Conor; McAuliffe, Eilish (2020-09-15)
    • Career tracking: factors affecting career choices and retention of Irish medical graduates / Edel McEntee ... [et al.]

      McEntee, Edel; Daly, Leslie; Clarke, Anna; Fitzpatrick, Patricia (University College Dublin, 2006)
    • Characterisation of GLUT4 trafficking in HeLa cells: comparable kinetics and orthologous trafficking mechanisms to 3T3-L1 adipocytes.

      Morris, Silke; Geoghegan, Niall D; Sadler, Jessica B A; Koester, Anna M; Black, Hannah L; Laub, Marco; Miller, Lucy; Heffernan, Linda; Simpson, Jeremy C; Mastick, Cynthia C; et al. (2020-03-05)
    • Ciliary Rab28 and the BBSome negatively regulate extracellular vesicle shedding.

      Akella, Jyothi S; Carter, Stephen P; Nguyen, Ken; Tsiropoulou, Sofia; Moran, Ailis L; Silva, Malan; Rizvi, Fatima; Kennedy, Breandan N; Hall, David H; Barr, Maureen M; et al. (2020-02-26)
      Cilia both receive and send information, the latter in the form of extracellular vesicles (EVs). EVs are nano-communication devices that influence cell, tissue, and organism behavior. Mechanisms driving ciliary EV biogenesis are almost entirely unknown. Here, we show that the ciliary G-protein Rab28, associated with human autosomal recessive cone-rod dystrophy, negatively regulates EV levels in the sensory organs of Caenorhabditis elegans in a cilia specific manner. Sequential targeting of lipidated Rab28 to periciliary and ciliary membranes is highly dependent on the BBSome and the prenyl-binding protein phosphodiesterase 6 subunit delta (PDE6D), respectively, and BBSome loss causes excessive and ectopic EV production. We also find that EV defective mutants display abnormalities in sensory compartment morphogenesis. Together, these findings reveal that Rab28 and the BBSome are key in vivo regulators of EV production at the periciliary membrane and suggest that EVs may mediate signaling between cilia and glia to shape sensory organ compartments. Our data also suggest that defects in the biogenesis of cilia-related EVs may contribute to human ciliopathies.
    • Clinical Decision Support Systems in Breast Cancer: A Systematic Review.

      Mazo, Claudia; Kearns, Cathriona; Mooney, Catherine; Gallagher, William M (2020-02-06)
    • A comparison of methods for the isolation and separation of extracellular vesicles from protein and lipid particles in human serum.

      Brennan, K; Martin, K; FitzGerald, S P; O'Sullivan, J; Wu, Y; Blanco, A; Richardson, C; Mc Gee, M M (2020-01-23)
    • Detection of a Novel, and Likely Ancestral, Tn-Like Element from a Human Saliva Metagenomic Library.

      Reynolds, Liam J; Anjum, Muna F; Roberts, Adam P (2020-05-14)
      Tn916 is a conjugative transposon (CTn) and the first reported and most well characterised of the Tn916/Tn1545 family of CTns. Tn916-like elements have a characteristic modular structure and different members of this family have been identified based on similarities and variations in these modules. In addition to carrying genes encoding proteins required for their conjugation, Tn916-like elements also carry accessory, antimicrobial resistance genes; most commonly the tetracycline resistance gene, tet(M). Our study aimed to identify and characterise tetracycline resistance genes from the human saliva metagenome using a functional metagenomic approach. We identified a tetracycline-resistant clone, TT31, the sequencing of which revealed it to encode both tet(M) and tet(L). Comparison of the TT31 sequence with the accessory, regulation, and recombination modules of other Tn916-like elements indicated that a partial Tn916-like element encoding a truncated orf9 was cloned in TT31. Analysis indicated that a previous insertion within the truncated orf9 created the full length orf9 found in most Tn916-like transposons; demonstrating that orf9 is, in fact, the result of a gene fusion event. Thus, we hypothesise that the Tn916-like element cloned in TT31 likely represents an ancestral Tn916.
    • Diabetes after pregnancy prevention trials: Systematic review for core outcome set development.

      O'Reilly, Sharleen L; Leonard, Yvonne; Dasgupta, Kaberi; Terkildsen Maindal, Helle (2020-01-14)
    • Differential DNA methylation correlates with response to methotrexate in rheumatoid arthritis.

      Nair, Nisha; Plant, Darren; Verstappen, Suzanne M; Isaacs, John D; Morgan, Ann W; Hyrich, Kimme L; Barton, Anne; Wilson, Anthony G
    • Double-blinded, randomized, and controlled study on the effects of canagliflozin after bariatric surgery: A pilot study.

      Kashyap, Sangeeta R; Kheniser, Karim; Aminian, Ali; Schauer, Philip; le Roux, Carel; Burguera, Bartolome (2020-03-17)
      Body mass index (-1.24 kg/m2) and body weight (-3.7 kg) were significantly reduced with canagliflozin therapy versus placebo. There were improvements in body fat composition as denoted by reductions in android (-3.00%) and truncal (-2.67%) fat. Also, there were differences in blood glucose and hemoglobin A1C at 6 months.
    • Early experiences of radiographers in Ireland during the COVID-19 crisis.

      Foley, Shane J; O'Loughlin, Anne; Creedon, Jill (2020-09-25)
    • Effects of once-weekly semaglutide vs once-daily canagliflozin on body composition in type 2 diabetes: a substudy of the SUSTAIN 8 randomised controlled clinical trial.

      McCrimmon, Rory J; Catarig, Andrei-Mircea; Frias, Juan P; Lausvig, Nanna L; le Roux, Carel W; Thielke, Desirée; Lingvay, Ildiko (2020-01-02)
      Adults (age ≥18 years) with type 2 diabetes, HbA1c 53-91 mmol/mol (7.0-10.5%), on a stable daily dose of metformin (≥1500 mg or maximum tolerated dose) and with an eGFR ≥60 ml min-1 [1.73 m]-2 were randomised 1:1 to semaglutide 1.0 mg once weekly and canagliflozin placebo once daily, or canagliflozin 300 mg once daily and semaglutide placebo once weekly. Body composition was assessed using whole-body DXA scans. The study participants and investigator remained blinded throughout the trial, and quality of DXA scans was evaluated in a blinded manner. Change from baseline to week 52 in total fat mass (kg) was the confirmatory efficacy endpoint.
    • Effects of skin care habits on the development of rosacea: A multi-center retrospective case-control survey in Chinese population.

      Huang, Ying-Xue; Li, Ji; Zhao, Zhi-Xiang; Zheng, Bo-Lan; Deng, Yu-Xuan; Shi, Wei; Steinhoff, Martin; Xie, Hong-Fu (2020-04-27)
    • Eligibility for heroin-assisted treatment (HAT) among people who inject opioids and are living with HIV in a Canadian setting.

      Klimas, Jan; Dong, Huiru; Fairbairn, Nadia; Socías, Eugenia; Barrios, Rolando; Wood, Evan; Kerr, Thomas; Montaner, Julio; Milloy, M-J (2018-02-07)
    • Equity and the financial costs of informal caregiving in palliative care: a critical debate.

      Gardiner, Clare; Robinson, Jackie; Connolly, Michael; Hulme, Claire; Kang, Kristy; Rowland, Christine; Larkin, Phil; Meads, David; Morgan, Tessa; Gott, Merryn (2020-05-19)