• Molecular mechanisms of gastric epithelial cell adhesion and injection of CagA by Helicobacter pylori

      Backert, Steffen; Clyne, Marguerite; Tegtmeyer, Nicole (2011-11-01)
      Abstract Helicobacter pylori is a highly successful pathogen uniquely adapted to colonize humans. Gastric infections with this bacterium can induce pathology ranging from chronic gastritis and peptic ulcers to gastric cancer. More virulent H. pylori isolates harbour numerous well-known adhesins (BabA/B, SabA, AlpA/B, OipA and HopZ) and the cag (cytotoxin-associated genes) pathogenicity island encoding a type IV secretion system (T4SS). The adhesins establish tight bacterial contact with host target cells and the T4SS represents a needle-like pilus device for the delivery of effector proteins into host target cells such as CagA. BabA and SabA bind to blood group antigen and sialylated proteins respectively, and a series of T4SS components including CagI, CagL, CagY and CagA have been shown to target the integrin β1 receptor followed by injection of CagA across the host cell membrane. The interaction of CagA with membrane-anchored phosphatidylserine may also play a role in the delivery process. While substantial progress has been made in our current understanding of many of the above factors, the host cell receptors for OipA, HopZ and AlpA/B during infection are still unknown. Here we review the recent progress in characterizing the interactions of the various adhesins and structural T4SS proteins with host cell factors. The contribution of these interactions to H. pylori colonization and pathogenesis is discussed.
    • Molecular-based detection of the gastrointestinal pathogen Campylobacter ureolyticus in unpasteurized milk samples from two cattle farms in Ireland

      Koziel, Monika; Lucey, Brigid; Bullman, Susan; Corcoran, Gerard D; Sleator, Roy D (2012-11-14)
      Abstract Campylobacter jejuni and coli are collectively regarded as the most prevalent cause of bacterial foodborne illness worldwide. An emerging species, Campylobacter ureolyticus has recently been detected in patients with gastroenteritis, however, the source of this organism has, until now, remained unclear. Herein, we describe the molecular-based detection of this pathogen in bovine faeces (1/20) and unpasteurized milk (6/47) but not in poultry (chicken wings and caeca). This is, to the best of our knowledge, the first report of the presence of this potential gastrointestinal pathogen in an animal source, possibly suggesting a route for its transmission to humans.
    • Monitoring post mortem changes in porcine muscle through 2-D DIGE proteome analysis of Longissimus muscle exudate

      Di Luca, Alessio; Elia, Giuliano; Mullen, Anne Maria; Hamill, Ruth M (2013-03-20)
      Abstract Background Meat quality is a complex trait influenced by a range of factors with post mortem biochemical processes highly influential in defining ultimate quality. High resolution two-dimensional DIfference Gel Electrophoresis (2-D DIGE) and Western blot were applied to study the influence of post mortem meat ageing on the proteome of pork muscle. Exudate collected from the muscle following centrifugation was analysed at three timepoints representing a seven day meat ageing period. Results The intensity of 136 spots varied significantly (p < 0.05) across this post mortem period and 40 spots were identified using mass spectrometry. The main functional categories represented were metabolic proteins, stress-related proteins, transport and structural proteins. Metabolic and structural proteins were generally observed to increase in abundance post mortem and many likely represent the accumulation of the degradation products of proteolytic enzyme activity. In contrast, stress-related proteins broadly decreased in abundance across the ageing period. Stress response proteins have protective roles in maintaining cellular integrity and a decline in their abundance over time may correlate with a reduction in cellular integrity and the onset of meat ageing. Since cellular conditions alter with muscle ageing, changes in solubility may also contribute to observed abundance profiles. Conclusions Muscle exudate provided valuable information about the pathways and processes underlying the post mortem ageing period, highlighting the importance of post mortem modification of proteins and their interaction for the development of meat quality traits.
    • Mothers and babies-reducing risk through audits and confidential enquiries

      Murphy, J F A (Irish Medical Journal (IMJ), 2012-07)
    • Mouth cancer awareness: what's at stake?

      Mills, Lia (Irish Dental Association, 2012-04)
    • Moving towards a mandate

      Hardiman, Ann-Marie (Journal of the Irish Dental Association, 2015-06)
    • MRSA bacteraemia: North/South study of MRSA in Ireland 1999.

      Mc Donald, P; Mitchell, E; Johnson, H; Rossney, A; Humphreys, H; Glynn, G; Burd, M; Doyle, D; Mc Donnell, R; Health Information Unit, Department of Public Health, Eastern Regional Health Authority, Dublin, Ireland. patriciamcdonald@eircom.net (2002-12)
      Retrospective aggregate data on all Staphylococcus aureus isolates recovered from blood cultures during 1998 were collected in both jurisdictions on the island of Ireland, Northern Ireland (North) and the Republic of Ireland (South), as part of the North/South Study of MRSA in Ireland 1999. A postal questionnaire was used to gather the data, and all diagnostic microbiology laboratories in the North and 98% of laboratories in the South participated. S. aureus bacteraemia occurred at rates of 20.4 per 100,000 population in the North and 24.5 per 100,000 in the South (missing data from one laboratory). In the North, 22% of patients who had blood cultures positive for S. aureus had methicillin-resistant S. aureus (MRSA) and 25% of S. aureus isolates were MRSA (some patients had more than one isolate). In the South, 31% of patients who had blood cultures positive for S. aureus had MRSA and 36% of S. aureus isolates were MRSA. There was a marked variation in rates between different regions. The percentage of patients with blood cultures positive for S. aureus that had MRSA was considerably lower in the North (22%) than in the South (31%), and in both jurisdictions was lower than that found in England and Wales in 1999 (37%). It is recommended that data on S. aureus bacteraemia and methicillin-resistance rates (already available in many laboratories) are gathered at regional and national level for the surveillance of antimicrobial resistance.
    • A multicentre survey of acute hospital nursing staff training in dementia care

      Coffey, Alice; Tyrrell, Mark; Buckley, Mary; Manning, Edmund; Browne, Vanessa; Barrett, Aoife; Timmons, Suzanne (Sciedu Press, 2014-07)
    • Multiple Myeloma and lifetime occupation: results from the EPILYMPH study

      Perrotta, Carla; Staines, Anthony; Codd, Mary; Kleefeld, Silke; Crowley, Dominique; T’ Mannetje, Andrea; Becker, Nicholas; Brennan, Paul; De Sanjosé, Silvia; Foretova, Lenka; et al. (2012-12-14)
      Abstract Background The EPILYMPH study applied a detailed occupational exposure assessment approach to a large multi-centre case–control study conducted in six European countries. This paper analysed multiple myeloma (MM) risk associated with level of education, and lifetime occupational history and occupational exposures, based on the EPILYMPH data set. Methods 277 MM cases and four matched controls per each case were included. Controls were randomly selected, matching for age (+/− 5 years), centre and gender. Lifetime occupations and lifetime exposure to specific workplace agents was obtained through a detailed questionnaire. Local industrial hygienists assessed likelihood and intensity for specific exposures. The odds ratio and 95% confidence intervals (OR, 95% CI) were calculated for level of education, individual occupations and specific exposures. Unconditional logistic regression models were run for individual occupations and exposures. Results A low level of education was associated with MM OR=1.68 (95% CI 1.02-2.76). An increased risk was observed for general farmers (OR=1.77; 95% CI 1.05-2.99) and cleaning workers (OR=1.69; 95% CI 1.04-2.72) adjusting for level of education. Risk was also elevated, although not significant, for printers (OR=2.06; 95% CI 0.97-4.34). Pesticide exposure over a period of ten years or more increased MM risk (OR=1.62; 95% CI 1.01-2.58). Conclusion These results confirm an association of MM with farm work, and indicate its association with printing and cleaning. While prolonged exposure to pesticides seems to be a risk factor for MM, an excess risk associated with exposure to organic solvents could not be confirmed.
    • A multiplex single nucleotide polymorphism typing assay for detecting mutations that result in decreased fluoroquinolone susceptibility in Salmonella enterica serovars Typhi and Paratyphi A.

      Song, Yajun; Roumagnac, Philippe; Weill, François-Xavier; Wain, John; Dolecek, Christiane; Mazzoni, Camila J; Holt, Kathryn E; Achtman, Mark; Environmental Research Institute, University College Cork, Lee Road, Cork, Ireland. (2010-08)
      OBJECTIVES: Decreased susceptibility to fluoroquinolones has become a major problem for the successful therapy of human infections caused by Salmonella enterica, especially the life-threatening typhoid and paratyphoid fevers. METHODS: By using Luminex xTAG beads, we developed a rapid, reliable and cost-effective multiplexed genotyping assay for simultaneously detecting 11 mutations in gyrA, gyrB and parE of S. enterica serovars Typhi and Paratyphi A that result in nalidixic acid resistance (Nal(R)) and/or decreased susceptibility to fluoroquinolones. RESULTS: This assay yielded unambiguous single nucleotide polymorphism calls on extracted DNA from 292 isolates of Salmonella Typhi (Nal(R) = 223 and Nal(S) = 69) and 106 isolates of Salmonella Paratyphi A (Nal(R) = 24 and Nal(S) = 82). All of the 247 Nal(R) Salmonella Typhi and Salmonella Paratyphi A isolates were found to harbour at least one of the target mutations, with GyrA Phe-83 as the most common one (143/223 for Salmonella Typhi and 18/24 for Salmonella Paratyphi A). We also identified three GyrB mutations in eight Nal(S) Salmonella Typhi isolates (six for GyrB Phe-464, one for GyrB Leu-465 and one for GyrB Asp-466), and mutations GyrB Phe-464 and GyrB Asp-466 seem to be related to the decreased ciprofloxacin susceptibility phenotype in Salmonella Typhi. This assay can also be used directly on boiled single colonies. CONCLUSIONS: The assay presented here would be useful for clinical and reference laboratories to rapidly screen quinolone-resistant isolates of Salmonella Typhi and Salmonella Paratyphi A, and decipher the underlying genetic changes for epidemiological purposes.
    • Mumps epidemiology in the mid-west of Ireland 2004-2008: increasing disease burden in the university/college setting.

      Whyte, D; O'Dea, F; McDonnell, C; O'Connell, N H; Callinan, S; Brosnan, E; Powell, J; Monahan, R; FitzGerald, R; Mannix, M; et al. (2009)
      Mumps is a contagious vaccine-preventable viral disease that is experiencing a revival in students attending second and third level colleges. Large mumps outbreaks have been reported in several countries despite the presence of childhood immunisation programmes over many years, including measles, mumps, and rubella (MMR) vaccination. In 2008, 1,377 cases of mumps were notified in Ireland and 1,734 in the first three months of 2009 (provisional data). This paper reviews the recent epidemiology of mumps in the Mid-West region of Ireland and highlights preventive measures. A substantial proportion of cases were not laboratory-confirmed and it is important that doctors continue to notify suspected cases. In the Irish Mid-West, data from enhanced surveillance shows a high proportion of mumps in the age group 15-24 years. Complications were uncommon and rarely severe. Where data were available, over half of the cases did not recall having received two doses of MMR, but most recalled one dose. Parents should continue to ensure children receive both MMR vaccinations so that uptake is optimal for protection. Steps were taken to increase awareness of the disease in the school, college and university settings. Preventive measures implemented to limit mumps transmission in the school/college setting over recent years included vaccination of close contacts, isolation for five days and hand hygiene.
    • Munchausen's syndrome--more common than we realize?

      Doherty, A M; Sheehan, J D; Department of Adult Psychiatry, UCD/Mater Misericordiae University Hospital, 63 Eccles St, Dublin 7. annedohertyemail@gmail.com (2010-06)
      Munchausen's syndrome is a condition whereby a patient deliberately simulates symptoms of an illness in order to gain admission to hospital and gain the sick role. It is an uncommon condition and is possibly underdiagnosed. This case-series examines the cases of three patients with Munchausen's syndrome who presented to a Dublin hospital within a four-month period. Two of the presentations involved the feigning of psychiatric symptoms. It is important that clinicians not only in psychiatry, but in all medical specialities have an awareness of this disorder, so that unnecessary procedures and treatments may be avoided.
    • Musculoskeletal modelling of muscle activation and applied external forces for the correction of scoliosis

      Curtin, Maurice; Lowery, Madeleine M (2014-04-07)
      Abstract Background This study uses biomechanical modelling and computational optimization to investigate muscle activation in combination with applied external forces as a treatment for scoliosis. Bracing, which incorporates applied external forces, is the most popular non surgical treatment for scoliosis. Non surgical treatments which make use of muscle activation include electrical stimulation, postural control, and therapeutic exercises. Electrical stimulation has been largely dismissed as a viable treatment for scoliosis, although previous studies have suggested that it can potentially deliver similarly effective corrective forces to the spine as bracing. Methods The potential of muscle activation for scoliosis correction was investigated over different curvatures both with and without the addition of externally applied forces. The five King’s classifications of scoliosis were investigated over a range of Cobb angles. A biomechanical model of the spine was used to represent various scoliotic curvatures. Optimization was applied to the model to reduce the curves using combinations of both deep and superficial muscle activation and applied external forces. Results Simulating applied external forces in combination with muscle activation at low Cobb angles (< 20 degrees) over the 5 King’s classifications, it was possible to reduce the magnitude of the curve by up to 85% for classification 4, 75% for classifications 3 and 5, 65% for classification 2, and 60% for classification 1. The reduction in curvature was less at larger Cobb angles. For King’s classifications 1 and 2, the serratus, latissimus dorsi, and trapezius muscles were consistently recruited by the optimization algorithm for activation across all Cobb angles. When muscle activation and external forces were applied in combination, lower levels of muscle activation or less external force was required to reduce the curvature of the spine, when compared with either muscle activation or external force applied in isolation. Conclusions The results of this study suggest that activation of superficial and deep muscles may be effective in reducing spinal curvature at low Cobb angles when muscle groups are selected for activation based on the curve type. The findings further suggest the potential for a hybrid treatment involving combined muscle activation and applied external forces at larger Cobb angles.
    • Mutation of a common amino acid in NKX2.5 results in dilated cardiomyopathy in two large families

      Hanley, Alan; Walsh, Katie A; Joyce, Caroline; McLellan, Michael A; Clauss, Sebastian; Hagen, Amaya; Shea, Marisa A; Tucker, Nathan R; Lin, Honghuang; Fahy, Gerard J; et al. (2016-11-17)
      Abstract Background The genetic basis for dilated cardiomyopathy (DCM) can be difficult to determine, particularly in familial cases with complex phenotypes. Next generation sequencing may be useful in the management of such cases. Methods We report two large families with pleiotropic inherited cardiomyopathy. In addition to DCM, the phenotypes included atrial and ventricular septal defects, cardiac arrhythmia and sudden death. Probands underwent whole exome sequencing to identify potentially causative variants. Results Each whole exome sequence yielded over 18,000 variants. We identified distinct mutations affecting a common amino acid in NKX2.5. Segregation analysis of the families support the pathogenic role of these variants. Conclusion Our study emphasizes the utility of next generation sequencing in identifying causative mutations in complex inherited cardiac disease. We also report a novel pathogenic NKX2.5 mutation.
    • Mutation of a common amino acid in NKX2.5 results in dilated cardiomyopathy in two large families

      Hanley, Alan; Walsh, Katie A; Joyce, Caroline; McLellan, Michael A; Clauss, Sebastian; Hagen, Amaya; Shea, Marisa A; Tucker, Nathan R; Lin, Honghuang; Fahy, Gerard J; et al. (BioMed Central, 2016-11-17)
      Abstract Background The genetic basis for dilated cardiomyopathy (DCM) can be difficult to determine, particularly in familial cases with complex phenotypes. Next generation sequencing may be useful in the management of such cases. Methods We report two large families with pleiotropic inherited cardiomyopathy. In addition to DCM, the phenotypes included atrial and ventricular septal defects, cardiac arrhythmia and sudden death. Probands underwent whole exome sequencing to identify potentially causative variants. Results Each whole exome sequence yielded over 18,000 variants. We identified distinct mutations affecting a common amino acid in NKX2.5. Segregation analysis of the families support the pathogenic role of these variants. Conclusion Our study emphasizes the utility of next generation sequencing in identifying causative mutations in complex inherited cardiac disease. We also report a novel pathogenic NKX2.5 mutation.
    • Mycobacterium tuberculosis infection induces non-apoptotic cell death of human dendritic cells

      Ryan, Ruth CM; O'Sullivan, Mary P; Keane, Joseph (2011-10-24)
      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.