http://hdl.handle.net/10147/76176 Search the Channel search http://www.lenus.ie/hse/simple-search http://hdl.handle.net/10147/196272 Title: Folic acid modified gelatine coated quantum dots as potential reagents for in vitro cancer diagnostics<br/><br/>Authors: Gerard, Valerie A; Maguire, Ciaran M; Bazou, Despina; Gun'ko, Yurii K<br/><br/>Abstract: Abstract Background Gelatine coating was previously shown to effectively reduce the cytotoxicity of CdTe Quantum Dots (QDs) which was a first step towards utilising them for biomedical applications. To be useful they also need to be target-specific which can be achieved by conjugating them with Folic Acid (FA). Results The modification of QDs with FA via an original "one-pot" synthetic route was proved successful by a range of characterisation techniques including UV-visible absorption spectroscopy, Photoluminescence (PL) emission spectroscopy, fluorescence life-time measurements, Transmission Electron Microscopy (TEM) and Dynamic Light Scattering (DLS). The resulting nanocomposites were tested in Caco-2 cell cultures which over-express FA receptors. The presence of FA on the surface of QDs significantly improved the uptake by targeted cells. Conclusions The modification with folic acid enabled to achieve a significant cellular uptake and cytotoxicity towards a selected cancer cell lines (Caco-2) of gelatine-coated TGA-CdTe quantum dots, which demonstrated good potential for in vitro cancer diagnostics. http://hdl.handle.net/10147/196271 Title: Mycobacterium tuberculosis infection induces non-apoptotic cell death of human dendritic cells<br/><br/>Authors: Ryan, Ruth CM; O'Sullivan, Mary P; Keane, Joseph<br/><br/>Abstract: Abstract Background Dendritic cells (DCs) connect innate and adaptive immunity, and are necessary for an efficient CD4+ and CD8+ T cell response after infection with Mycobacterium tuberculosis (Mtb). We previously described the macrophage cell death response to Mtb infection. To investigate the effect of Mtb infection on human DC viability, we infected these phagocytes with different strains of Mtb and assessed viability, as well as DNA fragmentation and caspase activity. In parallel studies, we assessed the impact of infection on DC maturation, cytokine production and bacillary survival. Results Infection of DCs with live Mtb (H37Ra or H37Rv) led to cell death. This cell death proceeded in a caspase-independent manner, and without nuclear fragmentation. In fact, substrate assays demonstrated that Mtb H37Ra-induced cell death progressed without the activation of the executioner caspases, 3/7. Although the death pathway was triggered after infection, the DCs successfully underwent maturation and produced a host-protective cytokine profile. Finally, dying infected DCs were permissive for Mtb H37Ra growth. Conclusions Human DCs undergo cell death after infection with live Mtb, in a manner that does not involve executioner caspases, and results in no mycobactericidal effect. Nonetheless, the DC maturation and cytokine profile observed suggests that the infected cells can still contribute to TB immunity. http://hdl.handle.net/10147/192755 Title: Working alliance, interpersonal trust and perceived coercion in mental health review hearings.<br/><br/>Authors: Donnelly, Vidis; Lynch, Aideen; Mohan, Damian; Kennedy, Harry G<br/><br/>Abstract: Abstract Background There is some evidence that when mental health commitment hearings are held in accordance with therapeutic jurisprudence principles they are perceived as less coercive, and more just in their procedures leading to improved treatment adherence and fewer hospital readmissions. This suggests an effect of the hearing on therapeutic relationships. We compared working alliance and interpersonal trust in clinicians and forensic patients, whose continued detentions were reviewed by two different legal review bodies according to their legal category. Methods The hearings were rated as positive or negative by patients and treating psychiatrists using the MacArthur scales for perceived coercion, perceived procedural justice (legal and medical) and for the impact of the hearing. We rated Global assessment of Function (GAF), Positive and Negative Symptom Scale (PANSS), Working Alliance Inventory (WAI) and Interpersonal Trust in Physician (ITP) scales six months before the hearing and repeated the WAI and ITP two weeks before and two weeks after the hearing, for 75 of 83 patients in a forensic medium and high secure hospital. Results Psychiatrists agreed with patients regarding the rating of hearings. Patients rated civil hearings (MHTs) more negatively than hearings under insanity legislation (MHRBs). Those reviewed by MHTs had lower scores for WAI and ITP. However, post-hearing WAI and ITP scores were not different from baseline and pre-hearing scores. Using the receiver operating characteristic, baseline WAI and ITP scores predicted how patients would rate the hearings, as did baseline GAF and PANSS scores. Conclusions There was no evidence that positively perceived hearings improved WAI or ITP, but some evidence showed that negatively perceived hearings worsened them. Concentrating on functional recovery and symptom remission remains the best strategy for improved therapeutic relationships. http://hdl.handle.net/10147/192726 Title: Synchronous presentation of acute acalculous cholecystitis and appendicitis: a case report<br/><br/>Authors: Sahebally, Shaheel M; Burke, John P; Nolan, Niamh; Latiff, Amir<br/><br/>Abstract: Abstract Introduction Acute acalculous cholecystitis is traditionally associated with elderly or critically ill patients. Case presentation We present the case of an otherwise healthy 23-year-old Caucasian man who presented with acute right-sided abdominal pain. An ultrasound examination revealed evidence of acute acalculous cholecystitis. A laparoscopy was undertaken and the dual pathologies of acute acalculous cholecystitis and acute appendicitis were discovered and a laparoscopic cholecystectomy and appendectomy were performed. Conclusion Acute acalculous cholecystitis is a rare clinical entity in young, healthy patients and this report describes the unusual association of acute acalculous cholecystitis and appendicitis. A single stage combined laparoscopic appendectomy and cholecystectomy is an effective treatment modality. http://hdl.handle.net/10147/192753 Title: Exploring the contribution of efflux on the resistance to fluoroquinolones in clinical isolates of Staphylococcus aureus<br/><br/>Authors: Costa, Sofia SANTOS; Falcao, Celeste; Viveiros, Miguel; Machado, Diana; Martins, Marta; Melo-Cristino, Jose; Amaral, Leonard; Couto, Isabel<br/><br/>Abstract: Abstract Background Antimicrobial resistance mediated by efflux systems is still poorly characterized in Staphylococcus aureus, despite the description of several efflux pumps (EPs) for this bacterium. In this work we used several methodologies to characterize the efflux activity of 52 S. aureus isolates resistant to ciprofloxacin collected in a hospital in Lisbon, Portugal, in order to understand the role played by these systems in the resistance to fluoroquinolones. Results Augmented efflux activity was detected in 12 out of 52 isolates and correlated with increased resistance to fluoroquinolones. Addition of efflux inhibitors did not result in the full reversion of the fluoroquinolone resistance phenotype, yet it implied a significant decrease in the resistance levels, regardless of the type(s) of mutation(s) found in the quinolone-resistance determining region of grlA and gyrA genes, which accounted for the remaining resistance that was not efflux-mediated. Expression analysis of the genes coding for the main efflux pumps revealed increased expression only in the presence of inducing agents. Moreover, it showed that not only different substrates can trigger expression of different EP genes, but also that the same substrate can promote a variable response, according to its concentration. We also found isolates belonging to the same clonal type that showed different responses towards drug exposure, thus evidencing that highly related clinical isolates may diverge in the efflux-mediated response to noxious agents. The data gathered by real-time fluorometric and RT-qPCR assays suggest that S. aureus clinical isolates may be primed to efflux antimicrobial compounds. Conclusions The results obtained in this work do not exclude the importance of mutations in resistance to fluoroquinolones in S. aureus, yet they underline the contribution of efflux systems for the emergence of high-level resistance. All together, the results presented in this study show the potential role played by efflux systems in the development of resistance to fluoroquinolones in clinical isolates of S. aureus. http://hdl.handle.net/10147/192395 Title: Comparison of midwife-led and consultant-led care of healthy women at low risk of childbirth complications in the Republic of Ireland: a randomised trial<br/><br/>Authors: Begley, Cecily; Devane, Declan; Clarke, Mike; McCann, Colette; Hughes, Patricia; Reilly, Mary; Maguire, Roisin; Higgins, Shane; Finan, Alan; Gormally, Siobhan; Doyle, Miriam<br/><br/>Abstract: Abstract Background No midwifery-led units existed in Ireland before 2004. The aim of this study was to compare midwife-led (MLU) versus consultant-led (CLU) care for healthy, pregnant women without risk factors for labour and delivery. Methods An unblinded, pragmatic randomised trial was designed, funded by the Health Service Executive (Dublin North-East). Following ethical approval, all women booking prior to 24 weeks of pregnancy at two maternity hospitals with 1,300-3,200 births annually in Ireland were assessed for trial eligibility.1,653 consenting women were centrally randomised on a 2:1 ratio to MLU or CLU care, (1101:552). 'Intention-to-treat' analysis was used to compare 9 key neonatal and maternal outcomes. Results No statistically significant difference was found between MLU and CLU in the seven key outcomes: caesarean birth (163 [14.8%] vs 84 [15.2%]; relative risk (RR) 0.97 [95% CI 0.76 to 1.24]), induction (248 [22.5%] vs 138 [25.0%]; RR 0.90 [0.75 to 1.08]), episiotomy (126 [11.4%] vs 68 [12.3%]; RR 0.93 [0.70 to 1.23]), instrumental birth (139 [12.6%] vs 79 [14.3%]; RR 0.88 [0.68 to 1.14]), Apgar scores &lt; 8 (10 [0.9%] vs 9 [1.6%]; RR 0.56 [0.23 to 1.36]), postpartum haemorrhage (144 [13.1%] vs 75 [13.6%]; RR 0.96 [0.74 to 1.25]); breastfeeding initiation (616 [55.9%] vs 317 [57.4%]; RR 0.97 [0.89 to 1.06]). MLU women were significantly less likely to have continuous electronic fetal monitoring (397 [36.1%] vs 313 [56.7%]; RR 0.64 [0.57 to 0.71]), or augmentation of labour (436 [39.6%] vs 314 [56.9%]; RR 0.50 [0.40 to 0.61]). Conclusions Midwife-led care, as practised in this study, is as safe as consultant-led care and is associated with less intervention during labour and delivery. Trial registration number ISRCTN: ISRCTN14973283 http://hdl.handle.net/10147/190070 Title: Alzheimer's disease: synaptic dysfunction and Abeta<br/><br/>Authors: Shankar, Ganesh M; Walsh, Dominic M<br/><br/>Abstract: Abstract Synapse loss is an early and invariant feature of Alzheimer's disease (AD) and there is a strong correlation between the extent of synapse loss and the severity of dementia. Accordingly, it has been proposed that synapse loss underlies the memory impairment evident in the early phase of AD and that since plasticity is important for neuronal viability, persistent disruption of plasticity may account for the frank cell loss typical of later phases of the disease. Extensive multi-disciplinary research has implicated the amyloid &#946;-protein (A&#946;) in the aetiology of AD and here we review the evidence that non-fibrillar soluble forms of A&#946; are mediators of synaptic compromise. We also discuss the possible mechanisms of A&#946; synaptotoxicity and potential targets for therapeutic intervention. http://hdl.handle.net/10147/190069 Title: Assessing the role of long-term LHRH agonist (Eligard 45mg) in managing localised prostatic adenocarcinoma<br/><br/>Authors: Rangaswamy, G; Ibrahim, N; Thirion, P<br/><br/>Description: A team from the Radiation Oncology Department at St. Luke's Hospital, Dublin, present a case of high risk localised adenocarcinoma of the prostate and discuss the role of leuprorelin acetate (Eligard) in the management of a case http://hdl.handle.net/10147/189826 Title: Synergizing metabolic flux analysis and nucleotide sugar metabolism to understand the control of glycosylation of recombinant protein in CHO cells<br/><br/>Authors: Burleigh, Susan C; van de Laar, Teun; Stroop, Corne JM; van Grunsven, Wout MJ; O'Donoghue, Niaobh; Rudd, Pauline M; Davey, Gavin P<br/><br/>Abstract: Abstract Background The glycosylation of recombinant proteins can be altered by a range of parameters including cellular metabolism, metabolic flux and the efficiency of the glycosylation process. We present an experimental set-up that allows determination of these key processes associated with the control of N-linked glycosylation of recombinant proteins. Results Chinese hamster ovary cells (CHO) were cultivated in shake flasks at 0 mM glutamine and displayed a reduced growth rate, glucose metabolism and a slower decrease in pH, when compared to other glutamine-supplemented cultures. The N-linked glycosylation of recombinant human chorionic gonadotrophin (HCG) was also altered under these conditions; the sialylation, fucosylation and antennarity decreased, while the proportion of neutral structures increased. A continuous culture set-up was subsequently used to understand the control of HCG glycosylation in the presence of varied glutamine concentrations; when glycolytic flux was reduced in the absence of glutamine, the glycosylation changes that were observed in shake flask culture were similarly detected. The intracellular content of UDP-GlcNAc was also reduced, which correlated with a decrease in sialylation and antennarity of the N-linked glycans attached to HCG. Conclusions The use of metabolic flux analysis illustrated a case of steady state multiplicity, where use of the same operating conditions at each steady state resulted in altered flux through glycolysis and the TCA cycle. This study clearly demonstrated that the control of glycoprotein microheterogeneity may be examined by use of a continuous culture system, metabolic flux analysis and assay of intracellular nucleotides. This system advances our knowledge of the relationship between metabolic flux and the glycosylation of biotherapeutics in CHO cells and will be of benefit to the bioprocessing industry. http://hdl.handle.net/10147/189816 Title: Cross-Sectional Analysis of Levels and Patterns of Objectively Measured Sedentary Time in Adolescent Females<br/><br/>Authors: Harrington, Deirdre M.; Dowd, Kieran P.; Bourke, Alan K.; Donnelly, Alan E.<br/><br/>Abstract: Abstract Background Adolescent females have been highlighted as a particularly sedentary population and the possible negative effects of a sedentary lifestyle are being uncovered. However, much of the past sedentary research is based on self-report or uses indirect methods to quantity sedentary time. Total time spent sedentary and the possible intricate sedentary patterns of adolescent females have not been described using objective and direct measure of body inclination. The objectives of this article are to examine the sedentary levels and patterns of a group of adolescent females using the ActivPAL&#8482; and to highlight possible differences in sedentary levels and patterns across the week and within the school day. A full methodological description of how the data was analyzed is also presented. Methods One hundred and eleven adolescent females, age 15-18 yrs, were recruited from urban and rural areas in the Republic of Ireland. Participants wore an ActivPAL physical activity monitor for a 7.5 day period. The ActivPAL directly reports total time spent sitting/lying every 15 seconds and accumulation (frequency and duration) of sedentary activity was examined using a customized MATLAB &#174; computer software programme. Results While no significant difference was found in the total time spent sitting/lying over the full 24 hour day between weekday and weekend day (18.8 vs. 18.9 hours; p = .911), significantly more sedentary bouts of 1 to 5 minutes and 21 to 40 minutes in duration were accumulated on weekdays compared to weekend days (p &lt; .001). The mean length of each sedentary bout was also longer (9.8 vs. 8.8 minutes; p &lt; .001). When school hours (9 am-3 pm) and after school hours (4 pm-10 pm) were compared, there was no difference in total time spent sedentary (3.9 hours; p = .796) but the pattern of accumulation of the sedentary time differed. There were a greater number of bouts of &gt; 20 minutes duration during school hours than after school hours (4.7 vs. 3.5 bouts; p &lt; .001) while after school time consisted of shorter bouts &lt; 20 minutes. Conclusions School is highlighted as a particularly sedentary setting for adolescent females. Interventions to decrease sedentary time at school and the use of wearable devices which distinguish posture should be encouraged when examining sedentary patterns and behaviors in this population.