• Cross-feeding by Bifidobacterium breve UCC2003 during co-cultivation with Bifidobacterium bifidum PRL2010 in a mucin-based medium

      Egan, Muireann; O’Connell Motherway, Mary; Kilcoyne, Michelle; Kane, Marian; Joshi, Lokesh; Ventura, Marco; van Sinderen, Douwe (2014-11-25)
      Abstract Background Bifidobacteria constitute a specific group of commensal bacteria that commonly inhabit the mammalian gastrointestinal tract. Bifidobacterium breve UCC2003 was previously shown to utilize a variety of plant/diet/host-derived carbohydrates, including cellodextrin, starch and galactan, as well as the mucin and HMO-derived monosaccharide, sialic acid. In the current study, we investigated the ability of this strain to utilize parts of a host-derived source of carbohydrate, namely the mucin glycoprotein, when grown in co-culture with the mucin-degrading Bifidobacterium bifidum PRL2010. Results B. breve UCC2003 was shown to exhibit growth properties in a mucin-based medium, but only when grown in the presence of B. bifidum PRL2010, which is known to metabolize mucin. A combination of HPAEC-PAD and transcriptome analyses identified some of the possible monosaccharides and oligosaccharides which support this enhanced co-cultivation growth/viability phenotype. Conclusion This study describes the potential existence of a gut commensal relationship between two bifidobacterial species. We demonstrate the in vitro ability of B. breve UCC2003 to cross-feed on sugars released by the mucin-degrading activity of B. bifidum PRL2010, thus advancing our knowledge on the metabolic adaptability which allows the former strain to colonize the (infant) gut by its extensive metabolic abilities to (co-)utilize available carbohydrate sources.
    • Cross-Sectional Analysis of Levels and Patterns of Objectively Measured Sedentary Time in Adolescent Females

      Harrington, Deirdre M.; Dowd, Kieran P.; Bourke, Alan K.; Donnelly, Alan E. (2011-10-28)
      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™ 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 ® 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 < .001). The mean length of each sedentary bout was also longer (9.8 vs. 8.8 minutes; p < .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 > 20 minutes duration during school hours than after school hours (4.7 vs. 3.5 bouts; p < .001) while after school time consisted of shorter bouts < 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.
    • A Cross-Sectional Study of Antibiotic Prescribing for Childhood Upper Respiratory Tract Infections in Irish General Practice

      Maguire, F; Murphy, ME; Rourke, R; Morgan, F; Brady, G; Byrne, E; O’Callaghan, ME (Irish Medical Journal, 2018-11)
    • Cross-sectional validation of the Aging Perceptions Questionnaire: a multidimensional instrument for assessing self-perceptions of aging.

      Barker, Maja; O'Hanlon, Ann; McGee, Hannah M; Hickey, Anne; Conroy, Ronan M; Department of Psychology, Division of Population Health Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland. maja.barker@gmail.com (2007)
      BACKGROUND: Self-perceptions of aging have been implicated as independent predictors of functional disability and mortality in older adults. In spite of this, research on self-perceptions of aging is limited. One reason for this is the absence of adequate measures. Specifically, there is a need to develop a measure that is theoretically-derived, has good psychometric properties, and is multidimensional in nature. The present research seeks to address this need by adopting the Self-Regulation Model as a framework and using it to develop a comprehensive, multi-dimensional instrument for assessing self-perceptions of aging. This study describes the validation of this newly-developed instrument, the Aging Perceptions Questionnaire (APQ). METHODS: Participants were 2,033 randomly selected community-dwelling older (+65 yrs) Irish adults who completed the APQ alongside measures of physical and psychological health. The APQ assesses self-perceptions of aging along eight distinct domains or subscales; seven of these examine views about own aging, these are: timeline chronic, timeline cyclical, consequences positive, consequences negative, control positive, control negative, and emotional representations; the eighth domain is the identity domain and this examines the experience of health-related changes. RESULTS: Mokken scale analysis showed that the majority of items within the views about aging subscales were strongly scalable. Confirmatory factor analysis also indicated that the model provided a good fit for the data. Overall, subscales had good internal reliabilities. Hierarchical linear regression was conducted to investigate the independent contribution of APQ subscales to physical and psychological health and in doing so determine the construct validity of the APQ. Results showed that self-perceptions of aging were independently related to physical and psychological health. Mediation testing also supported a role for self-perceptions of aging as partial mediators in the relationship between indices of physical functioning and physical and psychological health outcomes. CONCLUSION: Findings support the complex and multifaceted nature of the aging experience. The good internal reliability and construct validity of the subscales suggests that the APQ is a promising instrument that can enable a theoretically informed, multidimensional assessment of self-perceptions of aging. The potential role of self-perceptions of aging in facilitating physical and psychological health in later life is also highlighted.
    • Crowding and delivery of healthcare in emergency departments: the European perspective.

      Jayaprakash, Namita; O'Sullivan, Ronan; Bey, Tareg; Ahmed, Suleman S; Lotfipour, Shahram; St. Vincent's University Hospital, Department of Emergency Medicine, Dublin, Ireland. (2009-11)
      Emergency department (ED) crowding is a multifactorial problem, resulting in increased ED waiting times, decreased patient satisfaction and deleterious domino effects on the entire hospital. Although difficult to define and once limited to anecdotal evidence, crowding is receiving more attention as attempts are made to quantify the problem objectively. It is a worldwide phenomenon with regional influences, as exemplified when analyzing the problem in Europe compared to that of the United States. In both regions, an aging population, limited hospital resources, staff shortages and delayed ancillary services are key contributors; however, because the structure of healthcare differs from country to country, varying influences affect the issue of crowding. The approach to healthcare delivery as a right of all people, as opposed to a free market commodity, depends on governmental organization and appropriation of funds. Thus, public funding directly influences potential crowding factors, such as number of hospital beds, community care facilities, and staffing. Ultimately ED crowding is a universal problem with distinctly regional root causes; thus, any approach to address the problem must be tailored to regional influences.
    • Crowdsourcing, citizen sensing and Sensor Web technologies for public and environmental health surveillance and crisis management: trends, OGC standards and application examples

      Kamel Boulos, Maged N; Resch, Bernd; Crowley, David N; Breslin, John G; Sohn, Gunho; Burtner, Russ; Pike, William A; Jezierski, Eduardo; Chuang, Kuo-Yu Slayer (2011-12-21)
      Abstract 'Wikification of GIS by the masses' is a phrase-term first coined by Kamel Boulos in 2005, two years earlier than Goodchild's term 'Volunteered Geographic Information'. Six years later (2005-2011), OpenStreetMap and Google Earth (GE) are now full-fledged, crowdsourced 'Wikipedias of the Earth' par excellence, with millions of users contributing their own layers to GE, attaching photos, videos, notes and even 3-D (three dimensional) models to locations in GE. From using Twitter in participatory sensing and bicycle-mounted sensors in pervasive environmental sensing, to creating a 100,000-sensor geo-mashup using Semantic Web technology, to the 3-D visualisation of indoor and outdoor surveillance data in real-time and the development of next-generation, collaborative natural user interfaces that will power the spatially-enabled public health and emergency situation rooms of the future, where sensor data and citizen reports can be triaged and acted upon in real-time by distributed teams of professionals, this paper offers a comprehensive state-of-the-art review of the overlapping domains of the Sensor Web, citizen sensing and 'human-in-the-loop sensing' in the era of the Mobile and Social Web, and the roles these domains can play in environmental and public health surveillance and crisis/disaster informatics. We provide an in-depth review of the key issues and trends in these areas, the challenges faced when reasoning and making decisions with real-time crowdsourced data (such as issues of information overload, "noise", misinformation, bias and trust), the core technologies and Open Geospatial Consortium (OGC) standards involved (Sensor Web Enablement and Open GeoSMS), as well as a few outstanding project implementation examples from around the world.
    • Crystal structure of the lytic CHAPK domain of the endolysin LysK from Staphylococcus aureus bacteriophage K

      Sanz-Gaitero, Marta; Keary, Ruth; Garcia-Doval, Carmela; Coffey, Aidan; van Raaij, Mark J (2014-07-26)
      Abstract Background Bacteriophages encode endolysins to lyse their host cell and allow escape of their progeny. Endolysins are also active against Gram-positive bacteria when applied from the outside and are thus attractive anti-bacterial agents. LysK, an endolysin from staphylococcal phage K, contains an N-terminal cysteine-histidine dependent amido-hydrolase/peptidase domain (CHAPK), a central amidase domain and a C-terminal SH3b cell wall-binding domain. CHAPK cleaves bacterial peptidoglycan between the tetra-peptide stem and the penta-glycine bridge. Methods The CHAPK domain of LysK was crystallized and high-resolution diffraction data was collected both from a native protein crystal and a methylmercury chloride derivatized crystal. The anomalous signal contained in the derivative data allowed the location of heavy atom sites and phase determination. The resulting structures were completed, refined and analyzed. The presence of calcium and zinc ions in the structure was confirmed by X-ray fluorescence emission spectroscopy. Zymogram analysis was performed on the enzyme and selected site-directed mutants. Results The structure of CHAPK revealed a papain-like topology with a hydrophobic cleft, where the catalytic triad is located. Ordered buffer molecules present in this groove may mimic the peptidoglycan substrate. When compared to previously solved CHAP domains, CHAPK contains an additional lobe in its N-terminal domain, with a structural calcium ion, coordinated by residues Asp45, Asp47, Tyr49, His51 and Asp56. The presence of a zinc ion in the active site was also apparent, coordinated by the catalytic residue Cys54 and a possible substrate analogue. Site-directed mutagenesis was used to demonstrate that residues involved in calcium binding and of the proposed active site were important for enzyme activity. Conclusions The high-resolution structure of the CHAPK domain of LysK was determined, suggesting the location of the active site, the substrate-binding groove and revealing the presence of a structurally important calcium ion. A zinc ion was found more loosely bound. Based on the structure, we propose a possible reaction mechanism. Future studies will be aimed at co-crystallizing CHAPK with substrate analogues and elucidating its role in the complete LysK protein. This, in turn, may lead to the design of site-directed mutants with altered activity or substrate specificity.
    • The cumulative effect of core lifestyle behaviours on the prevalence of hypertension and dyslipidemia.

      Villegas, Raquel; Kearney, Patricia M; Perry, Ivan J; Department of Epidemiology and Public Health, University College Cork, Cork, Ireland. raquel.villegas@Vanderbilt.Edu (2008)
      BACKGROUND: Most cardiovascular disease (CVD) occurs in the presence of traditional risk factors, including hypertension and dyslipidemia, and these in turn are influenced by behavioural factors such as diet and lifestyle. Previous research has identified a group at low risk of CVD based on a cluster of inter-related factors: body mass index (BMI) < 25 Kg/m2, moderate exercise, alcohol intake, non-smoking and a favourable dietary pattern. The objective of this study was to determine whether these factors are associated with a reduced prevalence of hypertension and dyslipidemia in an Irish adult population. METHODS: The study was a cross-sectional survey of 1018 men and women sampled from 17 general practices. Participants completed health, lifestyle and food frequency questionnaires and provided fasting blood samples for analysis of glucose and insulin. We defined a low risk group based on the following protective factors: BMI <25 kg/m2; waist-hip ratio (WHR) <0.85 for women and <0.90 for men; never smoking status; participants with medium to high levels of physical activity; light alcohol consumption (3.5-7 units of alcohol/week) and a "prudent" diet. Dietary patterns were assessed by cluster analysis. RESULTS: We found strong significant inverse associations between the number of protective factors and systolic blood pressure, diastolic blood pressure and dyslipidemia. The prevalence odds ratio of hypertension in persons with 1, 2, 3, > or = 4 protective factors relative to those with none, were 1.0, 0.76, 0.68 and 0.34 (trend p < 0.01). The prevalence odds ratio of dyslipidemia in persons with 1, 2, 3, > or = 4 protective factors relative to those with none were 0.83, 0.98, 0.49 and 0.24 (trend p = 0.001). CONCLUSION: Our findings of a strong inverse association between low risk behaviours and two of the traditional risk factors for CVD highlight the importance of 'the causes of the causes' and the potential for behaviour modification in CVD prevention at a population level.
    • Cumulative radiation exposure in children with cystic fibrosis.

      O'Reilly, R; Ryan, S; Donoghue, V; Saidlear, C; Twomey, E; Slattery, D M; Children's University Hospital, Temple St, Dublin 1. roreilly@imperial.ac.uk (2010-02)
      This retrospective study calculated the cumulative radiation dose for children with cystic fibrosis (CF) attending a tertiary CF centre. Information on 77 children with a mean age of 9.5 years, a follow up time of 658 person years and 1757 studies including 1485 chest radiographs, 215 abdominal radiographs and 57 computed tomography (CT) scans, of which 51 were thoracic CT scans, were analysed. The average cumulative radiation dose was 6.2 (0.04-25) mSv per CF patient. Cumulative radiation dose increased with increasing age and number of CT scans and was greater in children who presented with meconium ileus. No correlation was identified between cumulative radiation dose and either lung function or patient microbiology cultures. Radiation carries a risk of malignancy and children are particularly susceptible. Every effort must be made to avoid unnecessary radiation exposure in these patients whose life expectancy is increasing.
    • Curating the innate immunity interactome.

      Lynn, David J; Chan, Calvin; Naseer, Misbah; Yau, Melissa; Lo, Raymond; Sribnaia, Anastasia; Ring, Giselle; Que, Jaimmie; Wee, Kathleen; Winsor, Geoffrey L; et al. (2010)
      The innate immune response is the first line of defence against invading pathogens and is regulated by complex signalling and transcriptional networks. Systems biology approaches promise to shed new light on the regulation of innate immunity through the analysis and modelling of these networks. A key initial step in this process is the contextual cataloguing of the components of this system and the molecular interactions that comprise these networks. InnateDB (http://www.innatedb.com) is a molecular interaction and pathway database developed to facilitate systems-level analyses of innate immunity.
    • Curcumin induces apoptosis-independent death in oesophageal cancer cells.

      O'Sullivan-Coyne, G; O'Sullivan, GC; O'Donovan, TR; Piwocka, K; McKenna, SL; Leslie C. Quick Laboratory, Cork Cancer Research Centre, BioSciences Institute, University College Cork and Mercy University Hospital, Cork, Ireland. (2009-10-06)
      Background:Oesophageal cancer incidence is increasing and survival rates remain extremely poor. Natural agents with potential for chemoprevention include the phytochemical curcumin (diferuloylmethane). We have examined the effects of curcumin on a panel of oesophageal cancer cell lines.Methods:MTT (3-(4,5-dimethyldiazol-2-yl)-2,5 diphenyl tetrazolium bromide) assays and propidium iodide staining were used to assess viability and DNA content, respectively. Mitotic catastrophe (MC), apoptosis and autophagy were defined by both morphological criteria and markers such as MPM-2, caspase 3 cleavage and monodansylcadaverine (MDC) staining. Cyclin B and poly-ubiquitinated proteins were assessed by western blotting.Results:Curcumin treatment reduces viability of all cell lines within 24 h of treatment in a 5-50 muM range. Cytotoxicity is associated with accumulation in G2/M cell-cycle phases and distinct chromatin morphology, consistent with MC. Caspase-3 activation was detected in two out of four cell lines, but was a minor event. The addition of a caspase inhibitor zVAD had a marginal or no effect on cell viability, indicating predominance of a non-apoptotic form of cell death. In two cell lines, features of both MC and autophagy were apparent. Curcumin-responsive cells were found to accumulate poly-ubiquitinated proteins and cyclin B, consistent with a disturbance of the ubiquitin-proteasome system. This effect on a key cell-cycle checkpoint regulator may be responsible for the mitotic disturbances and consequent cytotoxicity of this drug.Conclusion:Curcumin can induce cell death by a mechanism that is not reliant on apoptosis induction, and thus represents a promising anticancer agent for prevention and treatment of oesophageal cancer.British Journal of Cancer advance online publication, 6 October 2009; doi:10.1038/sj.bjc.6605308 www.bjcancer.com.
    • Current knowledge and future directions of TLR and NOD signaling in sepsis

      Foley, Niamh M; Wang, Jian; Redmond, H P; Wang, Jiang H (2015-01-07)
      Abstract The incidence of sepsis is increasing over time, along with an increased risk of dying from the condition. Sepsis care costs billions annually in the United States. Death from sepsis is understood to be a complex process, driven by a lack of normal immune homeostatic functions and excessive production of proinflammatory cytokines, which leads to multi-organ failure. The Toll-like receptor (TLR) family, one of whose members was initially discovered in Drosophila, performs an important role in the recognition of microbial pathogens. These pattern recognition receptors (PRRs), upon sensing invading microorganisms, activate intracellular signal transduction pathways. NOD signaling is also involved in the recognition of bacteria and acts synergistically with the TLR family in initiating an efficient immune response for the eradication of invading microbial pathogens. TLRs and NOD1/NOD2 respond to different pathogen-associated molecular patterns (PAMPs). Modulation of both TLR and NOD signaling is an area of research that has prompted much excitement and debate as a therapeutic strategy in the management of sepsis. Molecules targeting TLR and NOD signaling pathways exist but regrettably thus far none have proven efficacy from clinical trials.
    • Current practice in the referral of individuals with suspected dementia for neuroimaging by general practitioners in Ireland and Wales

      Ciblis, Aurelia S.; Butler, Marie-Louise; Quinn, Catherine; Clare, Linda; Bokde, Arun L. W.; Mullins, Paul G.; McNulty, Jonathan P. (2016-03-23)
    • Current trends in Irish perinatal mortality.

      Mahony, R; Foley, M E; O'Herlihy, C; National Maternity Hospital, Holies St., Dublin 2. (2010-06)
      This was a retrospective review of normally formed perinatal deaths among 176,620 births at the National Maternity Hospital (1984-2007). Prelabor stillbirths were categorised by presumed cause of death including unexplained, intrauterine growth retardation (IUGR), placental abruption, red cell alloimmunisation (RCA) and deaths related to prematurity. Peripartum deaths included intrapartum and first week neonatal deaths. The post-mortem rate, initially almost 100%, fell to 60%. Data were analysed using the Mantel-Haenszel chi square test for trends. In the study period there was a significant reduction in the PNM, largely because of a fall in death related to prematurity, term peripartum death, death at 42 weeks or greater, placental abruption, death related to IUGR and RCA (P < 0.01). Overall the unexplained still birth rate was unchanged throughout the study period (p = 0.8) despite a highly significant (p < 0.001) increase in obstetric intervention particularly induction of labor and caesarean section.
    • A cycle of brain gain, waste and drain - a qualitative study of non-EU migrant doctors in Ireland

      Humphries, Niamh; Tyrrell, Ella; McAleese, Sara; Bidwell, Posy; Thomas, Steve; Normand, Charles; Brugha, Ruairi (Human Resources for Health, 2013)
    • A cycle of brain gain, waste and drain - a qualitative study of non-EU migrant doctors in Ireland

      Humphries, Niamh; Tyrrell, Ella; McAleese, Sara; Bidwell, Posy; Thomas, Steve; Normand, Charles; Brugha, Ruairi (2013-12-09)
      Abstract Background Ireland is heavily reliant on non-EU migrant health workers to staff its health system. Shortages of locally trained health workers and policies which facilitate health worker migration have contributed to this trend. This paper provides insight into the experiences of non-EU migrant doctors in the Irish health workforce. Method In-depth interviews were conducted with 37 non-EU migrant doctors in Ireland in 2011/2012. Results Respondents believed they had been recruited to fill junior hospital doctor ‘service’ posts. These posts are unpopular with locally trained doctors due to the limited career progression they provide. Respondents felt that their hopes for career progression and postgraduate training in Ireland had gone unrealised and that they were becoming de-skilled. As a result, most respondents were actively considering onward migration from Ireland. Discussion & conclusions Failure to align the expectations of non-EU migrant doctors with the requirements of the health system has resulted in considerable frustration and a cycle of brain gain, waste and drain. The underlying reasons for high mobility into and out of the Irish medical workforce must be addressed if this cycle is to be broken. The heavy reliance on non-EU migrant doctors to staff the medical workforce has distracted from the underlying workforce challenges facing the Irish medical workforce.
    • The cyclooxygenase-2 inhibitor celecoxib and alveolar osteitis

      Sukhun, Dr Jehad (Irish Dental Association, 2011-02)
    • Cylindroma of the breast: a case report and review of the literature

      Mahmoud, Amr; Hill, David H; O'Sullivan, Martin J; Bennett, Michael W (2009-09-02)
      Abstract Cylindroma of the breast is a very rare lesion which is morphological and immunophenotypically identical to benign dermal cylindroma. We report a breast cylindroma in a previously healthy 62 year old female detected through a national breast screening program. The patient had no significant family or past medical history, and specifically no history of breast or skin diseases. The tumor consisted of well circumscribed islands of epithelial cells surrounded by a dense membrane material, and focally containing hyaline globules. At low power the islands of tumour cells formed a "jig-saw" pattern, which is typical of cylindroma, but was present within normal breast parenchyma and no had direct connection with the overlying skin. Two distinct cell populations, smaller peripheral basaloid cells and larger central cells with vesicular chromatin, were highlighted by immunohistochemistry for p63 and cytokeratin-7 respectively. Immunohistochemistry for ER, PR, and Her2/neu was negative in tumour cells. We discuss the nine previously reported cases and the distinction of breast cylindroma from adenoid cystic carcinoma, the main differential diagnosis.