• Gestatinal weight gain and birthweight

      Turner, MJ; Farah, N (Irish Medical Journal, 2010-12)
    • Getting the balance right: a randomised controlled trial of physiotherapy and Exercise Interventions for ambulatory people with multiple sclerosis.

      Coote, Susan; Garrett, Maria; Hogan, Neasa; Larkin, Aidan; Saunders, Jean; Department of Physiotherapy, University of Limerick, Limerick, Ireland. susan.coote@ul.ie (2009)
      BACKGROUND: People with Multiple Sclerosis have a life long need for physiotherapy and exercise interventions due to the progressive nature of the disease and their greater risk of the complications of inactivity. The Multiple Sclerosis Society of Ireland run physiotherapy, yoga and exercise classes for their members, however there is little evidence to suggest which form of physical activity optimises outcome for people with the many and varied impairments associated with MS. METHODS AND DESIGN: This is a multi-centre, single blind, block randomised, controlled trial. Participants will be recruited via the ten regional offices of MS Ireland. Telephone screening will establish eligibility and stratification according to the mobility section of the Guys Neurological Disability Scale. Once a block of people of the same strand in the same geographical region have given consent, participants will be randomised. Strand A will concern individuals with MS who walk independently or use one stick to walk outside. Participants will be randomised to yoga, physiotherapy led exercise class, fitness instructor led exercise class or to a control group who don't change their exercise habits.Strand B will concern individuals with MS who walk with bilateral support or a rollator, they may use a wheelchair for longer distance outdoors. Participants will be randomised to 1:1 Physiotherapist led intervention, group intervention led by Physiotherapist, group yoga intervention or a control group who don't change their exercise habits. Participants will be assessed by physiotherapist who is blind to the group allocation at week 1, week 12 (following 10 weeks intervention or control), and at 12 week follow up. The primary outcome measure for both strands is the Multiple Sclerosis Impact Scale. Secondary outcomes are Modified Fatigue Impact Scale, 6 Minute Walk test, and muscle strength measured with hand held dynamometry. Strand B will also use Berg Balance Test and the Modified Ashworth Scale. Confounding variables such as sensation, coordination, proprioception, range of motion and other impairments will be recorded at initial assessment. DISCUSSION: Data analysis will analyse change in each group, and the differences between groups. Sub group analysis may be performed if sufficient numbers are recruited. TRIAL REGISTRATION: ISRCTN77610415.
    • Ghrelin in the human myometrium

      O'Brien, Margaret; Earley, Padraig; Morrison, John J.; Smith, Terry J. (2010-05-28)
      Abstract Background Ghrelin is a 28-amino acid octanolyated peptide, synthesised primarily in the stomach. It stimulates growth hormone release, food intake and exhibits many other diverse effects. Our group have previously determined that ghrelin inhibited human contractility in vitro. The aim of this study therefore, was to investigate the expression of ghrelin, its receptor, the growth hormone secretagogue receptor type 1 (GHS-R1), ghrelin O-acyltransferase (GOAT) which catalyses ghrelin octanoylation, prohormone convertase 1/3 (PC1/3) responsible for pro-ghrelin processing, in human myometrium, during pregnancy prior to labour, during labour and in the non-pregnant state. Modulation of ghrelin and ghrelin receptor expression in cultured myometrial cells was also investigated. Methods mRNA and protein were isolated from human myometrium and the myometrial smooth muscle cell line hTERT-HM; and real-time fluorescence RT-PCR, western blotting and fluorescence microscopy performed. The effects of β-Estradiol and bacterial lipopolysaccharide (LPS) on hTERT-HM gene expression were evaluated by western blotting. Results We have reported for the first time the expression and processing of ghrelin, GHS-R1, GOAT and PC1/3 expression in human myometrium, and also the down-regulation of ghrelin mRNA and protein expression during labour. Furthermore, GHS-R1 protein expression significantly decreased at labour. Myometrial GOAT expression significantly increased during term non-labouring pregnancy in comparison to both non-pregnant and labouring myometrium. Mature PC1/3 protein expression was significantly decreased at term pregnancy and labour in comparison to non-pregnant myometrium. Ghrelin, GHS-R1, GOAT and PC1/3 mRNA and protein expression was also detected in the hTERT-HM cells. Ghrelin protein expression decreased upon LPS treatment in these cells while β-Estradiol treatment increased GHS-R1 expression. Conclusions Ghrelin processing occurred in the human myometrium at term pregnancy and in the non-pregnant state. GOAT expression which increased during term non-labouring pregnancy demonstrating a similar expression pattern to prepro-ghrelin and GHS-R1, decreased at labour, signifying possible myometrial ghrelin acylation. Moreover, the presence of PC1/3 may contribute to pro-ghrelin processing. These results along with the previous in vitro data suggest that myometrially-produced and processed ghrelin plays a significant autocrine or paracrine role in the maintenance of relaxation in this tissue during pregnancy. Furthermore, the significant uterine modulators LPS and β-Estradiol are involved in the regulation of ghrelin and ghrelin receptor expression respectively, in the human myometrium.
    • Ghrelin in the human myometrium.

      O'Brien, Margaret; Earley, Padraig; Morrison, John J; Smith, Terry J; National Centre for Biomedical and Engineering Science, Orbsen Building, National University of Ireland Galway, University Road, Galway, Ireland. margaret.obrien@nuigalway.ie (2010)
      BACKGROUND: Ghrelin is a 28-amino acid octanolyated peptide, synthesised primarily in the stomach. It stimulates growth hormone release, food intake and exhibits many other diverse effects. Our group have previously determined that ghrelin inhibited human contractility in vitro. The aim of this study therefore, was to investigate the expression of ghrelin, its receptor, the growth hormone secretagogue receptor type 1 (GHS-R1), ghrelin O-acyltransferase (GOAT) which catalyses ghrelin octanoylation, prohormone convertase 1/3 (PC1/3) responsible for pro-ghrelin processing, in human myometrium, during pregnancy prior to labour, during labour and in the non-pregnant state. Modulation of ghrelin and ghrelin receptor expression in cultured myometrial cells was also investigated. METHODS: mRNA and protein were isolated from human myometrium and the myometrial smooth muscle cell line hTERT-HM; and real-time fluorescence RT-PCR, western blotting and fluorescence microscopy performed. The effects of beta-Estradiol and bacterial lipopolysaccharide (LPS) on hTERT-HM gene expression were evaluated by western blotting. RESULTS: We have reported for the first time the expression and processing of ghrelin, GHS-R1, GOAT and PC1/3 expression in human myometrium, and also the down-regulation of ghrelin mRNA and protein expression during labour. Furthermore, GHS-R1 protein expression significantly decreased at labour. Myometrial GOAT expression significantly increased during term non-labouring pregnancy in comparison to both non-pregnant and labouring myometrium. Mature PC1/3 protein expression was significantly decreased at term pregnancy and labour in comparison to non-pregnant myometrium. Ghrelin, GHS-R1, GOAT and PC1/3 mRNA and protein expression was also detected in the hTERT-HM cells. Ghrelin protein expression decreased upon LPS treatment in these cells while beta-Estradiol treatment increased GHS-R1 expression. CONCLUSIONS: Ghrelin processing occurred in the human myometrium at term pregnancy and in the non-pregnant state. GOAT expression which increased during term non-labouring pregnancy demonstrating a similar expression pattern to prepro-ghrelin and GHS-R1, decreased at labour, signifying possible myometrial ghrelin acylation. Moreover, the presence of PC1/3 may contribute to pro-ghrelin processing. These results along with the previous in vitro data suggest that myometrially-produced and processed ghrelin plays a significant autocrine or paracrine role in the maintenance of relaxation in this tissue during pregnancy. Furthermore, the significant uterine modulators LPS and beta-Estradiol are involved in the regulation of ghrelin and ghrelin receptor expression respectively, in the human myometrium.
    • Giant cell tumour in the foot of a skeletally immature girl: a case report.

      Baker, Joseph F; Perera, Anthony; Kiely, Paul D; Lui, Darren F; Stephens, Michael M; Cappagh National Orthopaedic Hospital, Cappagh Road, Finglas, Dublin 11, Ireland. joseph.f.baker@gmail.com (2009-08)
      We present a case of delayed diagnosis of a benign giant cell tumour (GCT) of the third metatarsal in a skeletally immature girl. The patient underwent en bloc excision of the tumour. The tumour had replaced the third metatarsal and had infiltrated the surrounding soft tissue and the second and fourth metatarsal bases. Deep, lateral and medial margins were all involved. A high index of suspicion is needed when evaluating any tumours of the foot, because the compact structure of the foot may delay diagnosis. Early detection is important for avoiding amputation, as the hindfoot and midfoot are classified as one compartment and radical resection is impossible to achieve. Tumours grow faster in the foot than in other bones. GCT in this location and age-group are rare and should be considered in the differential diagnosis of a destructive bony lesion in skeletally immature patients.
    • Global endometrial transcriptomic profiling: transient immune activation precedes tissue proliferation and repair in healthy beef cows

      Foley, Cathriona; Chapwanya, Aspinas; Creevey, Christopher J; Narciandi, Fernando; Morris, Derek; Kenny, Elaine M; Cormican, Paul; Callanan, John J; O’Farrelly, Cliona; Meade, Kieran G (2012-09-18)
      Abstract Background All cows experience bacterial contamination and tissue injury in the uterus postpartum, instigating a local inflammatory immune response. However mechanisms that control inflammation and achieve a physiologically functioning endometrium, while avoiding disease in the postpartum cow are not succinctly defined. This study aimed to identify novel candidate genes indicative of inflammation resolution during involution in healthy beef cows. Previous histological analysis of the endometrium revealed elevated inflammation 15 days postpartum (DPP) which was significantly decreased by 30 DPP. The current study generated a genome-wide transcriptomic profile of endometrial biopsies from these cows at both time points using mRNA-Seq. The pathway analysis tool GoSeq identified KEGG pathways enriched by significantly differentially expressed genes at both time points. Novel candidate genes associated with inflammatory resolution were subsequently validated in additional postpartum animals using quantitative real-time PCR (qRT-PCR). Results mRNA-Seq revealed 1,107 significantly differentially expressed genes, 73 of which were increased 15 DPP and 1,034 were increased 30 DPP. Early postpartum, enriched immune pathways (adjusted P < 0.1) included the T cell receptor signalling pathway, graft-versus-host disease and cytokine-cytokine receptor interaction pathways. However 30 DPP, where the majority of genes were differentially expressed, the enrichment (adjusted P < 0.1) of tissue repair and proliferative activity pathways was observed. Nineteen candidate genes selected from mRNA-Seq results, were independently assessed by qRT-PCR in additional postpartum cows (5 animals) at both time points. SAA1/2, GATA2, IGF1, SHC2, and SERPINA14 genes were significantly elevated 30 DPP and are functionally associated with tissue repair and the restoration of uterine homeostasis postpartum. Conclusions The results of this study reveal an early activation of the immune response which undergoes a temporal functional change toward tissue proliferation and regeneration during endometrial involution in healthy postpartum cows. These molecular changes mirror the activation and resolution of endometrial inflammation during involution previously classified by the degree of neutrophil infiltration. SAA1/2, GATA2, IGF1, SHC2, and SERPINA14 genes may become potential markers for resolution of endometrial inflammation in the postpartum cow.
    • Global mental health: how are we doing?

      Hanna, Fahmy; Corrado, Barbui; Tarun, Dua; Lora, Antonio; van Regteren Altena, Marieke; Saxena, Shekhar (World Psychiatry, 2018-10)
    • Global MYCN transcription factor binding analysis in neuroblastoma reveals association with distinct E-box motifs and regions of DNA hypermethylation.

      Murphy, Derek M; Buckley, Patrick G; Bryan, Kenneth; Das, Sudipto; Alcock, Leah; Foley, Niamh H; Prenter, Suzanne; Bray, Isabella; Watters, Karen M; Higgins, Desmond; et al. (2009)
      BACKGROUND: Neuroblastoma, a cancer derived from precursor cells of the sympathetic nervous system, is a major cause of childhood cancer related deaths. The single most important prognostic indicator of poor clinical outcome in this disease is genomic amplification of MYCN, a member of a family of oncogenic transcription factors. METHODOLOGY: We applied MYCN chromatin immunoprecipitation to microarrays (ChIP-chip) using MYCN amplified/non-amplified cell lines as well as a conditional knockdown cell line to determine the distribution of MYCN binding sites within all annotated promoter regions. CONCLUSION: Assessment of E-box usage within consistently positive MYCN binding sites revealed a predominance for the CATGTG motif (p<0.0016), with significant enrichment of additional motifs CATTTG, CATCTG, CAACTG in the MYCN amplified state. For cell lines over-expressing MYCN, gene ontology analysis revealed enrichment for the binding of MYCN at promoter regions of numerous molecular functional groups including DNA helicases and mRNA transcriptional regulation. In order to evaluate MYCN binding with respect to other genomic features, we determined the methylation status of all annotated CpG islands and promoter sequences using methylated DNA immunoprecipitation (MeDIP). The integration of MYCN ChIP-chip and MeDIP data revealed a highly significant positive correlation between MYCN binding and DNA hypermethylation. This association was also detected in regions of hemizygous loss, indicating that the observed association occurs on the same homologue. In summary, these findings suggest that MYCN binding occurs more commonly at CATGTG as opposed to the classic CACGTG E-box motif, and that disease associated over expression of MYCN leads to aberrant binding to additional weaker affinity E-box motifs in neuroblastoma. The co-localization of MYCN binding and DNA hypermethylation further supports the dual role of MYCN, namely that of a classical transcription factor affecting the activity of individual genes, and that of a mediator of global chromatin structure.
    • Glucose homeostasis in the intensive care: the end of a cycle

      Murphy, JFA (Irish Medical Journal (IMJ), 2012-10)
    • Glucose metabolism determines resistance of cancer cells to bioenergetic crisis after cytochrome-c release.

      Huber, Heinrich J; Dussmann, Heiko; Kilbride, Seán M; Rehm, Markus; Prehn, Jochen H M; Systems Biology Group, Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland. (2011-03-01)
      Many anticancer drugs activate caspases via the mitochondrial apoptosis pathway. Activation of this pathway triggers a concomitant bioenergetic crisis caused by the release of cytochrome-c (cyt-c). Cancer cells are able to evade these processes by altering metabolic and caspase activation pathways. In this study, we provide the first integrated system study of mitochondrial bioenergetics and apoptosis signalling and examine the role of mitochondrial cyt-c release in these events. In accordance with single-cell experiments, our model showed that loss of cyt-c decreased mitochondrial respiration by 95% and depolarised mitochondrial membrane potential ΔΨ(m) from -142 to -88 mV, with active caspase-3 potentiating this decrease. ATP synthase was reversed under such conditions, consuming ATP and stabilising ΔΨ(m). However, the direction and level of ATP synthase activity showed significant heterogeneity in individual cancer cells, which the model explained by variations in (i) accessible cyt-c after release and (ii) the cell's glycolytic capacity. Our results provide a quantitative and mechanistic explanation for the protective role of enhanced glucose utilisation for cancer cells to avert the otherwise lethal bioenergetic crisis associated with apoptosis initiation.
    • ‘Going between worlds’: Travelling with children with complex needs

      Nicholl, Honor; Nursing and Midwifery Department, University of Dublin, Trinity College (2013)
    • Goltz Syndrome: Taurodontism

      McNamara, CM; Trotman, CA; Hahessy, A (1996)
    • Good practice in mental health care for socially marginalised groups in Europe: a qualitative study of expert views in 14 countries

      Priebe, Stefan; Matanov, Aleksandra; Schor, Ruth; Straßmayr, Christa; Barros, Henrique; Barry, Margaret M; Díaz-Olalla, José M; Gabor, Edina; Greacen, Tim; Holcnerová, Petra; et al. (2012-03-28)
      Abstract Background Socially marginalised groups tend to have higher rates of mental disorders than the general population and can be difficult to engage in health care. Providing mental health care for these groups represents a particular challenge, and evidence on good practice is required. This study explored the experiences and views of experts in 14 European countries regarding mental health care for six socially marginalised groups: long-term unemployed; street sex workers; homeless; refugees/asylum seekers; irregular migrants and members of the travelling communities. Methods Two highly deprived areas were selected in the capital cities of 14 countries, and experts were interviewed for each of the six marginalised groups. Semi-structured interviews with case vignettes were conducted to explore experiences of good practice and analysed using thematic analysis. Results In a total of 154 interviews, four components of good practice were identified across all six groups: a) establishing outreach programmes to identify and engage with individuals with mental disorders; b) facilitating access to services that provide different aspects of health care, including mental health care, and thus reducing the need for further referrals; c) strengthening the collaboration and co-ordination between different services; and d) disseminating information on services both to marginalised groups and to practitioners in the area. Conclusions Experts across Europe hold similar views on what constitutes good practice in mental health care for marginalised groups. Care may be improved through better service organisation, coordination and information.
    • GPs' perspectives on the management of patients with multimorbidity: systematic review and synthesis of qualitative research.

      Sinnott, Carol; Mc Hugh, Sheena; Browne, John; Bradley, Colin; UCC (2013)
      To synthesise the existing published literature on the perceptions of general practitioners (GPs) or their equivalent on the clinical management of multimorbidity and determine targets for future research that aims to improve clinical care in multimorbidity.
    • Grading operative findings at laparoscopic cholecystectomy- a new scoring system

      Sugrue, Michael; Sahebally, Shaheel M; Ansaloni, Luca; Zielinski, Martin D (2015-03-08)
      Abstract Introduction Variation in outcomes from surgery is a major challenge and defining surgical findings may help set benchmarks, which currently do not exist in laparoscopic cholecystectomy. This study outlines a new surgical scoring system incorporating key operative findings. Methods English language studies (from January 1965 to July 2014) pertaining to severity scoring and predictors of difficult laparoscopic cholecystectomy were searched for in PubMed, Embase and Cochrane databases using the search terms ‘Laparoscopic cholecystectomy or Lap chole’ and/or ‘Scoring Index or Grading system or Prediction of difficulty or Conversion to open’ in various combinations. Cross-referencing from papers retrieved in the original search identified additional articles. Results Sixteen published papers report a gallbladder (GB) scoring system, but all relate to pre-operative clinical and imaging findings, rather than operative findings. The current scoring system, using operative findings incorporates the appearance of the GB, presence of GB distension, ease of access, potential biliary complications and time taken to identify cystic duct and artery. A score of <2 would imply mild difficulty, 2–4 moderate, 5–7 severe and 8–10 extreme. Conclusion This paper reports one of the first operative classifications of findings at laparoscopic cholecystectomy. It has the potential to allow benchmarks for international collaboration of operative and patient outcomes in patients undergoing laparoscopic cholecystectomy.
    • Greedy feature selection for glycan chromatography data with the generalized Dirichlet distribution

      Galligan, Marie C; Saldova, Radka; Campbell, Matthew P; Rudd, Pauline M; Murphy, Thomas B (2013-05-07)
      Abstract Background Glycoproteins are involved in a diverse range of biochemical and biological processes. Changes in protein glycosylation are believed to occur in many diseases, particularly during cancer initiation and progression. The identification of biomarkers for human disease states is becoming increasingly important, as early detection is key to improving survival and recovery rates. To this end, the serum glycome has been proposed as a potential source of biomarkers for different types of cancers. High-throughput hydrophilic interaction liquid chromatography (HILIC) technology for glycan analysis allows for the detailed quantification of the glycan content in human serum. However, the experimental data from this analysis is compositional by nature. Compositional data are subject to a constant-sum constraint, which restricts the sample space to a simplex. Statistical analysis of glycan chromatography datasets should account for their unusual mathematical properties. As the volume of glycan HILIC data being produced increases, there is a considerable need for a framework to support appropriate statistical analysis. Proposed here is a methodology for feature selection in compositional data. The principal objective is to provide a template for the analysis of glycan chromatography data that may be used to identify potential glycan biomarkers. Results A greedy search algorithm, based on the generalized Dirichlet distribution, is carried out over the feature space to search for the set of “grouping variables” that best discriminate between known group structures in the data, modelling the compositional variables using beta distributions. The algorithm is applied to two glycan chromatography datasets. Statistical classification methods are used to test the ability of the selected features to differentiate between known groups in the data. Two well-known methods are used for comparison: correlation-based feature selection (CFS) and recursive partitioning (rpart). CFS is a feature selection method, while recursive partitioning is a learning tree algorithm that has been used for feature selection in the past. Conclusions The proposed feature selection method performs well for both glycan chromatography datasets. It is computationally slower, but results in a lower misclassification rate and a higher sensitivity rate than both correlation-based feature selection and the classification tree method.
    • Greening healthcare: systematic implementation of environmental programmes in a university teaching hospital

      Ryan-Fogarty, Yvonne; O'Regan, Bernadette; Moles, Richard; University of Limerick (Elsevier, 2016-07)
    • 'Groping through the fog': a metasynthesis of women's experiences on VBAC (Vaginal birth after Caesarean section)

      Lundgren, Ingela; Begley, Cecily; Gross, Mechthild M; Bondas, Terese (2012-08-21)
      Abstract Background Vaginal birth after Caesarean section (VBAC) is a relevant question for a large number of women due to the internationally rising Caesarean section (CS) rate. There is a great deal of research based on quantitative studies but few qualitative studies about women's experiences. Method A metasynthesis based on the interpretative meta ethnography method was conducted. The inclusion criterion was peer-review qualitative articles from different disciplines about women's experiences of VBAC. Eleven articles were checked for quality, and eight articles were included in the synthesis. Results The included studies were from Australia (four), UK (three), and US (one), and studied women's experience in relation to different aspects of VBAC; decision-making whether to give birth vaginally, the influence of health professionals on decision-making, reason for trying a vaginal birth, experiences when choosing VBAC, experiences of giving birth vaginally, and giving birth with CS when preferring VBAC. The main results are presented with the metaphor groping through the fog; for the women the issue of VBAC is like being in a fog, where decision-making and information from the health care system and professionals, both during pregnancy and the birth, is unclear and contrasting. The results are further presented with four themes: ‘to be involved in decision about mode of delivery is difficult but important,’ ‘vaginal birth has several positive aspects mainly described by women,’ ‘vaginal birth after CS is a risky project,’ and ‘own strong responsibility for giving birth vaginally'. Conclusion In order to promote VBAC, more studies are needed from different maternity settings and countries about women's experiences. Women need evidence-based information not only about the risks involved but also positive aspects of VBAC.
    • Group follow-up compared to individual clinic visits after structured education for type 1 diabetes: a cluster randomised controlled trial.

      Dinneen, Sean F; O'Hara, Mary Clare; Byrne, Molly; Smith, Diarmuid; Courtney, Christopher H; McGurk, Colm; Heller, Simon R; Newell, John; Coffey, Norma; Breen, Cathy; et al. (Diabetes research and clinical practice, 2013-04)
      To compare the effectiveness of group follow-up with individual follow-up after participation in the Dose Adjustment for Normal Eating (DAFNE) structured education programme.
    • Growing Old in the Emergency Department

      Liston, P; Conyngham, G; Brady, M; Byrne, PJ; Gilligan, P (Irish Medical Journal, 2017-09)