• 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.
    • Admission Decision-Making in Hospital Emergency Departments: The Role of the Accompanying Person.

      Rance, Susanna; Westlake, Debra; Brant, Heather; Holme, Ingrid; Endacott, Ruth; Pinkney, Jonathan; Byng, Richard (2020-06-18)
    • Adverse outcome pathways as a tool for the design of testing strategies to support the safety assessment of emerging advanced materials at the nanoscale.

      Halappanavar, Sabina; van den Brule, Sybille; Nymark, Penny; Gaté, Laurent; Seidel, Carole; Valentino, Sarah; Zhernovkov, Vadim; Høgh Danielsen, Pernille; De Vizcaya, Andrea; Wolff, Henrik; et al. (2020-05-25)
    • 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)
    • Associations between the Home Environment, Feeding Practices and Children's Intakes of Fruit, Vegetables and Confectionary/Sugar-Sweetened Beverages.

      Bassul, Carolina; A Corish, Clare; M Kearney, John (2020-07-05)
      Within the home environment, parents influence their children's dietary intakes through their parenting and dietary practices, and the foods they make available/accessible. The aim of this cross-sectional study was to examine the associations between home environmental characteristics and children's dietary intakes. Three hundred and thirty-two children aged three-five years and their parents participated in the study. Home environmental characteristics, including parental control feeding practices, were explored using validated and standardized questionnaires such as the Child Feeding Questionnaire (CFQ), the Physical and Nutritional Home Environment Inventory (PNHEI) and the Healthy Home Survey (HHS). Parent and child food consumption was also measured. Pressure to eat from parents was associated with lower fruit intake in children (OR 0.67, 95% CI 0.47-0.96, p = 0.032). Greater variety of fruit available in the home increased the likelihood of fruit consumption in children (OR 1.35 95% CI 1.09-1.68, p = 0.005). Watching television for ≥1 h per day was associated with a decreased probability of children eating vegetables daily (OR 0.38, 95% CI 0.20-0.72, p = 0.003) and doubled their likelihood of consuming confectionary/sugar-sweetened beverages more than once weekly (OR 2.15, 95% CI 1.06-4.38, p = 0.034). Children whose parents had lower vegetable consumption were 59% less likely to eat vegetables daily. This study demonstrates that modifiable home environmental characteristics are significantly associated with children's dietary intakes.
    • Attitudes About Informed Consent: An Exploratory Qualitative Analysis of UK Psychotherapy Trainees.

      Blease, Charlotte R; Arnott, Tim; Kelley, John M; Proctor, Gillian; Kube, Tobias; Gaab, Jens; Locher, Cosima (2020-03-13)
      Background: Ethical informed consent to psychotherapy has recently been the subject of in-depth analysis among healthcare ethicists. Objective: This study aimed to explore counseling and psychotherapy students' views and understanding about informed consent to psychological treatments. Methods: Two focus groups were conducted with a total of 10 students enrolled in a Masters course in counseling and psychotherapy at a British university. Questions concerned participants' understanding of informed consent including judgments about client capacity; the kinds of information that should be disclosed; how consent might be obtained; and their experiences of informed consent, both as a client and as a therapist. Focus groups were audio-recorded, transcribed, and analyzed using qualitative content analysis. Coding was conducted independently by three authors. Results: Comments were classified into three main themes: (1) the reasons and justifications for informed consent; (2) informed consent processes; and (3) the hidden ethics curriculum. Some trainees expressed significant doubts about the importance of informed consent. However, participants also identified the need to establish the clients' voluntariness and their right to be informed about confidentiality issues. In general, the format and processes pertaining to informed consent raised considerable questions and uncertainties. Participants were unsure about rules surrounding client capacity; expressed misgivings about describing treatment techniques; and strikingly, most trainees were skeptical about the clinical relevance of the evidence-base in psychotherapy. Finally, trainees' experiences as clients within obligatory psychotherapy sessions were suggestive of a "hidden ethics curriculum"-referring to the unintended transmission of norms and practices within training that undermine the explicit guidance expressed in formal professional ethics codes. Some students felt coerced into therapy, and some reported not undergoing informed consent processes. Reflecting on work placements, trainees expressed mixed views, with some unclear about who was responsible for informed consent. Conclusions: This qualitative study presents timely information on psychotherapy students' views about informed consent to psychotherapy. Major gaps in students' ethical, conceptual, and procedural knowledge were identified, and comments suggested the influence of a hidden curriculum in shaping norms of practice. Implications: This exploratory study raises important questions about the preparedness of psychotherapy students to fulfill their ethical obligations.
    • Calcitriol and non-calcemic vitamin D analogue, 22-oxacalcitriol, attenuate developmental and pathological choroidal vasculature angiogenesis and .

      Merrigan, Stephanie L; Park, Bomina; Ali, Zaheer; Jensen, Lasse D; Corson, Timothy W; Kennedy, Breandán N (2020-02-04)
      Aberrant ocular angiogenesis can underpin vision loss in leading causes of blindness, including neovascular age-related macular degeneration and proliferative diabetic retinopathy. Current pharmacological interventions require repeated invasive administrations, may lack efficacy and are associated with poor patient compliance and tachyphylaxis. Vitamin D has de novo anti-angiogenic properties. Here, our aim was to validate the ocular anti-angiogenic activity of biologically active vitamin D, calcitriol, and selected vitamin D analogue, 22-oxacalcitriol. Calcitriol induced a significant reduction in ex vivo mouse choroidal fragment sprouting. Viability studies in a human RPE cell line suggested non-calcemic vitamin D analogues including 22-oxacalcitriol have less off-target anti-proliferative activity compared to calcitriol and other analogues. Thereafter, the anti-angiogenic activity of 22-oxacalcitriol was demonstrated in an ex vivo mouse choroidal fragment sprouting assay. In zebrafish larvae, 22-oxacalcitriol was found to be anti-angiogenic, inducing a dose-dependent reduction in choriocapillaris development. Subcutaneously administered calcitriol failed to attenuate mouse retinal vasculature development. However, calcitriol and 22-oxacalcitriol administered intraperitoneally, significantly attenuated lesion volume in the laser-induced choroidal neovascularisation mouse model. In summary, calcitriol and 22-oxacalcitriol attenuate ex vivo and in vivo choroidal vasculature angiogenesis. Therefore, vitamin D may have potential as an interventional treatment for ophthalmic neovascular indications.
    • 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)
    • The Cell Cycle Checkpoint System MAST(L)-ENSA/ARPP19-PP2A is Targeted by cAMP/PKA and cGMP/PKG in Anucleate Human Platelets.

      Kumm, Elena J; Pagel, Oliver; Gambaryan, Stepan; Walter, Ulrich; Zahedi, René P; Smolenski, Albert; Jurk, Kerstin (2020-02-18)
    • 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)
    • Children's unscheduled primary and emergency care in Ireland: a multimethod approach to understanding decision making, trends, outcomes and parental perspectives (CUPID): project protocol.

      McAuliffe, Eilish; Hamza, Moayed; McDonnell, Thérèse; Nicholson, Emma; De Brún, Aoife; Barrett, Michael; Brunsdon, Christopher; Bury, Gerard; Collins, Claire; Deasy, Conor; et al. (2020-08-13)
    • 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)
    • Comparing different domains of analysis for the characterisation of N-glycans on monoclonal antibodies.

      Carillo, Sara; Pérez-Robles, Raquel; Jakes, Craig; Ribeiro da Silva, Meire; Millán Martín, Silvia; Farrell, Amy; Navas, Natalia; Bones, Jonathan (2019-11-29)
    • Comparing the Usability and Acceptability of Wearable Sensors Among Older Irish Adults in a Real-World Context: Observational Study.

      Keogh, Alison; Dorn, Jonas F; Walsh, Lorcan; Calvo, Francesc; Caulfield, Brian (2020-04-20)