• Yersinia outer protein YopE affects the actin cytoskeleton in Dictyostelium discoideum through targeting of multiple Rho family GTPases

      Vlahou, Georgia; Schmidt, Oxana; Wagner, Bettina; Uenlue, Handan; Dersch, Petra; Rivero, Francisco; Weissenmayer, Barbara A (2009-07-14)
      Abstract Background All human pathogenic Yersinia species share a virulence-associated type III secretion system that translocates Yersinia effector proteins into host cells to counteract infection-induced signaling responses and prevent phagocytosis. Dictyostelium discoideum has been recently used to study the effects of bacterial virulence factors produced by internalized pathogens. In this study we explored the potential of Dictyostelium as model organism for analyzing the effects of ectopically expressed Yersinia outer proteins (Yops). Results The Yersinia pseudotuberculosis virulence factors YopE, YopH, YopM and YopJ were expressed de novo within Dictyostelium and their effects on growth in axenic medium and on bacterial lawns were analyzed. No severe effect was observed for YopH, YopJ and YopM, but expression of YopE, which is a GTPase activating protein for Rho GTPases, was found to be highly detrimental. GFP-tagged YopE expressing cells had less conspicuous cortical actin accumulation and decreased amounts of F-actin. The actin polymerization response upon cAMP stimulation was impaired, although chemotaxis was unaffected. YopE also caused reduced uptake of yeast particles. These alterations are probably due to impaired Rac1 activation. We also found that YopE predominantly associates with intracellular membranes including the Golgi apparatus and inhibits the function of moderately overexpressed RacH. Conclusion The phenotype elicited by YopE in Dictyostelium can be explained, at least in part, by inactivation of one or more Rho family GTPases. It further demonstrates that the social amoeba Dictyostelium discoideum can be used as an efficient and easy-to-handle model organism in order to analyze the function of a translocated GAP protein of a human pathogen.
    • You can’t be too careful

      Boynton, Sue (Irish Dental Association, 2017-02)
    • Young people and drugs: A review document

      Cox, Gemma; The Addiction Research Centre, Trinity College Dublin (The Addiction Research Centre, Trinity College Dublin, 2002-09)
    • Young women's decisions to accept chlamydia screening: influences of stigma and doctor-patient interactions

      Balfe, Myles; Brugha, Ruairi; O'Donovan, Diarmuid; O'Connell, Emer; Vaughan, Deirdre (2010-07-19)
      Abstract Background An understanding of the factors that encourage young women to accept, and discourage them from accepting, STI (sexually transmitted infection) testing is needed to underpin opportunistic screening programs for the STI Chlamydia trachomatis (opportunistic screening involves healthcare professionals offering chlamydia tests to people while they are attending health services for reasons that are usually unrelated to their sexual health). We conducted a qualitative study to identify and explore: how young women would feel about being offered opportunistic tests for chlamydia?; how young women would like to be offered screening, and who they wanted to be offered screening by?; and what factors would influence young women's partner notification preferences for chlamydia (who they would notify in the event of a positive diagnosis of chlamydia, how they would want to do this). Methods Semi-structured interviews with 35 young women between eighteen and twenty nine years of age. The study was conducted in the Dublin and Galway regions of the Republic of Ireland. Young adults were recruited from General Practice (GP) practices, Third Level College health services, Family Planning clinics and specialist STI treatment services. Results Respondents were worried that their identities would become stigmatised if they accepted screening. Younger respondents and those from lower socio-economic backgrounds had the greatest stigma-related concerns. Most respondents indicated that they would accept screening if it was offered to them, however; accepting screening was seen as a correct, responsible action to engage in. Respondents wanted to be offered screening by younger female healthcare professionals. Respondents were willing to inform their current partners about positive chlamydia diagnoses, but were more ambivalent about informing their previous partners. Conclusions If an effort is not put into reducing young women's stigma-related concerns the population coverage of Chlamydia screening might be reduced.
    • Young women's understanding of their sexual health needs

      Kavanagh, Roisin; Lawless, Jo Murphy; Letterkenny Women's Centre (Crisis Pregnancy Agency, 2006)
    • Younger age as a prognostic indicator in breast cancer: A cohort study

      Kheirelseid, Elrasheid A.H.; Boggs, Jennifer M.E.; Curran, Catherine; Glynn, Ronan W; Dooley, Carra; Sweeney, Karl J; Kerin, Michael J (2011-08-28)
      Abstract Background The debate continues as to whether younger women who present with breast cancer have a more aggressive form of disease and a worse prognosis. The objectives of this study were to determine the incidence of breast cancer in women under 40 years old and to analyse the clinicopathological characteristics and outcome compared to an older patient cohort. Methods Data was acquired from a review of charts and the prospectively reviewed GUH Department of Surgery database. Included in the study were 276 women diagnosed with breast cancer under the age of forty and 2869 women over forty. For survival analysis each women less than 40 was matched with two women over forty for both disease stage and grade. Results The proportion of women diagnosed with breast cancer under the age of forty in our cohort was 8.8%. In comparison to their older counterparts, those under forty had a higher tumour grade (p = 0.044) and stage (p = 0.046), a lower incidence of lobular tumours (p < 0.001), higher estrogen receptor negativity (p < 0.001) and higher HER2 over-expression (p = 0.002); there was no statistical difference as regards tumour size (p = 0.477). There was no significant difference in overall survival (OS) for both groups; and factors like tumour size (p = 0.026), invasion (p = 0.026) and histological type (p = 0.027), PR (p = 0.031) and HER2 (p = 0.002) status and treatment received were independent predictors of OS Conclusion Breast cancer in younger women has distinct histopathological characteristics; however, this does not result in a reduced survival in this population.
    • Youth alcohol and drug use in rural Ireland--parents' views.

      Van Hout, Marie Claire A; Waterford Institute of Technology, Waterford, Ireland. mcvh@eircom.net (2009-08-27)
      INTRODUCTION: Drug availability is increasing throughout Ireland due to a convergence of rural and urban cultures during the last decade of economic growth and prosperity. Rural Irish youth may now have a heightened risk for problematic alcohol and drug use due to increased exposure to drugs, urban contact with peer drug users, unstructured recreation time and poor parental monitoring. Rural parents may perceive their children to be less at risk, and often struggle more than their urban counterparts to identify and respond to their children's alcohol and drug use. The aim of this research was to provide an exploratory account of rural parents' perspectives on alcohol and illicit drug use among youth in Ireland. METHODS: A convenience sample of parents with adolescent children was selected at a parent-teacher evening at 3 rural schools, with the facilitation of school completion officers (34 mothers and 21 fathers, n = 55). Semi-structured interviews were conducted which included questions relating to the parents' perceptions of youth drug and alcohol use, both in terms of recreational and problematic use in their communities, levels of drug availability, risk perceptions, settings of adolescent substance use, service provision and drug information; and not necessarily with regard to their own children. Following transcription of the interviews, a content and thematic analysis was conducted in order to identify areas of similar and contrasting opinions, and various formulations were compared and contrasted in order to ground the information firmly in the data garnered. RESULTS: The results suggested parental concern with regard to increased rural drug exposure for youth in local rural communities. The majority of parents were aware of youth alcohol use but were concerned about all drugs, not aware of specific differences in drug-related risk, and had difficulty comprehending harm-reduction principles. Most parents recognised the need for greater parental monitoring, awareness of free time accountability, improved parent-child discourse, and visibility of services. CONCLUSION: Life in contemporary rural Ireland is influenced by dominant social changes in terms of the normalisation of alcohol and drug use in youth subcultures, with increased fragmentation of traditional rural family norms and values, emerging acceptability of alcohol and drug use in recreation time and the widespread availability of alcohol and drugs. There is a need to target rural parents using a community development approach in order to provide drug education, service visibility and family support for those experiencing problematic substance use.
    • Youth mental health in deprived urban areas: a Delphi study on the role of the GP in early intervention.

      Schaffalitzky, E; Leahy, D; Cullen, W; Gavin, B; Latham, L; O'Connor, R; Smyth, B P; O'Dea, E; Ryan, S; Graduate Entry Medical School, University of Limerick, Limerick, Ireland. (Irish journal of medical science, 2014-09-06)
      GPs have a key role in addressing youth mental health and this study highlights the key domains of this role and the key components of a complex intervention to support this role.
    • Youth-physical activity towards health: evidence and background to the development of the Y-PATH physical activity intervention for adolescents

      Belton, Sarahjane; O’ Brien, Wesley; Meegan, Sarah; Woods, Catherine; Issartel, Johann (2014-02-05)
      Abstract Background Despite known benefits of regular physical activity for health and well-being, many studies suggest that levels of physical activity in young people are low, and decline dramatically during adolescence. The purpose of the current research was to gather data on adolescent youth in order to inform the development of a targeted physical activity intervention. Methods Cross-sectional data on physical activity levels (using self report and accelerometry), psychological correlates of physical activity, anthropometic characteristics, and the fundamental movement skill proficiency of 256 youth (53% male, 12.40 ± 0.51 years) were collected. A subsample (n = 59) participated in focus group interviews to explore their perceptions of health and identify barriers and motivators to participation in physical activity. Results Findings indicate that the majority of youth (67%) were not accumulating the minimum 60 minutes of physical activity recommended daily for health, and that 99.5% did not achieve the fundamental movement skill proficiency expected for their age. Body mass index data showed that 25% of youth were classified as overweight or obese. Self-efficacy and physical activity attitude scores were significantly different (p < 0.05) between low, moderate and high active participants. Active and inactive youth reported differences in their perceived understanding of health and their barriers to physical activity participation, with active youth relating nutrition, exercise, energy and sports with the definition of ‘being healthy’, and inactive youth attributing primarily nutritional concepts to ‘being healthy’. Conclusions Data show a need for targeting low levels of physical activity in youth through addressing poor health related activity knowledge and low fundamental movement skill proficiency. The Y-PATH intervention was developed in accordance with the present study findings; details of the intervention format are presented.
    • You’re in it together

      Rattan, Raj (Journal of the Irish Dental Association, 2015-02)
    • α-1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8.

      Bergin, David A; Reeves, Emer P; Meleady, Paula; Henry, Michael; McElvaney, Oliver J; Carroll, Tomás P; Condron, Claire; Chotirmall, Sanjay H; Clynes, Martin; O'Neill, Shane J; McElvaney, Noel G; Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland. (2010-12-01)
      Hereditary deficiency of the protein α-1 antitrypsin (AAT) causes a chronic lung disease in humans that is characterized by excessive mobilization of neutrophils into the lung. However, the reason for the increased neutrophil burden has not been fully elucidated. In this study we have demonstrated using human neutrophils that serum AAT coordinates both CXCR1- and soluble immune complex (sIC) receptor-mediated chemotaxis by divergent pathways. We demonstrated that glycosylated AAT can bind to IL-8 (a ligand for CXCR1) and that AAT-IL-8 complex formation prevented IL-8 interaction with CXCR1. Second, AAT modulated neutrophil chemotaxis in response to sIC by controlling membrane expression of the glycosylphosphatidylinositol-anchored (GPI-anchored) Fc receptor FcγRIIIb. This process was mediated through inhibition of ADAM-17 enzymatic activity. Neutrophils isolated from clinically stable AAT-deficient patients were characterized by low membrane expression of FcγRIIIb and increased chemotaxis in response to IL-8 and sIC. Treatment of AAT-deficient individuals with AAT augmentation therapy resulted in increased AAT binding to IL-8, increased AAT binding to the neutrophil membrane, decreased FcγRIIIb release from the neutrophil membrane, and normalization of chemotaxis. These results provide new insight into the mechanism underlying the effect of AAT augmentation therapy in the pulmonary disease associated with AAT deficiency.