• A field guide to pandemic, epidemic and sporadic clones of methicillin-resistant Staphylococcus aureus.

      Monecke, Stefan; Coombs, Geoffrey; Shore, Anna C; Coleman, David C; Akpaka, Patrick; Borg, Michael; Chow, Henry; Ip, Margaret; Jatzwauk, Lutz; Jonas, Daniel; et al. (2011-04)
      In recent years, methicillin-resistant Staphylococcus aureus (MRSA) have become a truly global challenge. In addition to the long-known healthcare-associated clones, novel strains have also emerged outside of the hospital settings, in the community as well as in livestock. The emergence and spread of virulent clones expressing Panton-Valentine leukocidin (PVL) is an additional cause for concern. In order to provide an overview of pandemic, epidemic and sporadic strains, more than 3,000 clinical and veterinary isolates of MRSA mainly from Germany, the United Kingdom, Ireland, France, Malta, Abu Dhabi, Hong Kong, Australia, Trinidad & Tobago as well as some reference strains from the United States have been genotyped by DNA microarray analysis. This technique allowed the assignment of the MRSA isolates to 34 distinct lineages which can be clearly defined based on non-mobile genes. The results were in accordance with data from multilocus sequence typing. More than 100 different strains were distinguished based on affiliation to these lineages, SCCmec type and the presence or absence of PVL. These strains are described here mainly with regard to clinically relevant antimicrobial resistance- and virulence-associated markers, but also in relation to epidemiology and geographic distribution. The findings of the study show a high level of biodiversity among MRSA, especially among strains harbouring SCCmec IV and V elements. The data also indicate a high rate of genetic recombination in MRSA involving SCC elements, bacteriophages or other mobile genetic elements and large-scale chromosomal replacements.
    • First tooth, first visit, zero cavities: a review of the evidence as it applies to Ireland

      Duane, Brett; McGovern, Eleanor; Ní Chaollaí, Aifric; FitzGerald, Kirsten (Journal of Irish Dental Association, 2017-04)
      In recent years several studies have demonstrated that dental caries is already well established by the time a child reaches three years of age. In Scotland, for example, three-year-old children had a caries prevalence of 25%, with a higher rate of 32% in children living in deprived areas, when examined in 2007/2008.1 In England in 2013, 12% of three-year-old children had experienced dental decay and those children with dental disease had approximately three teeth that were decayed, missing or filled.
    • Focal seizures secondary to cortical dysplasia associated with isolated oral morphea and odontogenic carcinoma.

      McNamara, Patricia H; Toner, Mary; Kearns, Gerard; Keohane, Catherine; Daly, Peter; Doherty, Colin P; Department of Neurology, St. James's Hospital, Dublin, Ireland. pmcnamara2004@hotmail.com (Seizure : the journal of the British Epilepsy Association, 2013-03)
    • The forgotten profession.

      Stassen, Leo F A (2010-04)
    • From caffeine to fish waste: amine compounds present in food and drugs and their interactions with primary amine oxidase.

      Olivieri, Aldo; Rico, Daniel; Khiari, Zhied; Henehan, Gary; O'Sullivan, Jeff; Tipton, Keith; School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland. oliviera@tcd.ie (2011-07)
      Tissue bound primary amine oxidase (PrAO) and its circulating plasma-soluble form are involved, through their catalytic activity, in important cellular roles, including the adhesion of lymphocytes to endothelial cells during various inflammatory conditions, the regulation of cell growth and maturation, extracellular matrix deposition and maturation and glucose transport. PrAO catalyses the oxidative deamination of several xenobiotics and has been linked to vascular toxicity, due to the generation of cytotoxic aldehydes. In this study, a series of amines and aldehydes contained in food and drugs were tested via a high-throughput assay as potential substrates or inhibitors of bovine plasma PrAO. Although none of the compounds analyzed were found to be substrates for the enzyme, a series of molecules, including caffeine, the antidiabetics phenformin and tolbutamide and the antimicrobial pentamidine, were identified as PrAO inhibitors. Although the inhibition observed was in the millimolar and micromolar range, these data show that further work will be necessary to elucidate whether the interaction of ingested biogenic or xenobiotic amines with PrAO might adversely affect its biological roles.
    • Functional surgery of the temporomandibular joint with conscious sedation for "closed lock" using eminectomy as a treatment: a case series.

      Stassen, Leo F; O'Halloran, Michael; Dublin Dental School and Hospital, Lincoln Place, Dublin 2, Ireland. (2011-06)
      The purpose of this case series study was to evaluate the advantages and disadvantages of using local anesthesia and conscious sedation (CS) rather than general anesthesia (GA) for performing functional surgery on patients suffering from temporomandibular joint (TMJ) closed lock, using the eminectomy procedure. Performing this procedure using CS allows functional assessment of the TMJ meniscus at the time of surgery. The objectives of this study were to determine if this surgery is possible under CS, to determine the benefits of being able to see the meniscus in action, and to investigate the patients' acceptability for this form of anesthesia.
    • Fundamentals of occlusion and restorative dentistry. Part I: basic principles

      Warreth, Abdulhadi (Irish Dental Association (IDA), 2015-08)
      One of the goals of restorative treatment is maintenance and/or reestablishment of a good dental occlusion when the treatment is completed.1,2 Therefore, restorative treatment should be aimed at the achievement of smooth unhindered mandibular movements during function. The outcome should not result in an occlusal interference, nor should it lead to generation of excessive force on the teeth, the periodontal apparatus or the temporomandibular joints (TMJs).3,4 All members of the masticatory system should work in harmony and accommodate the changes in occlusal morphology of the finished restoration well.4 Therefore, dentists must have a sound knowledge of dental occlusion and masticatory systems. This article provides clarification of the basic principles of dental occlusion, as well as an overview of this subject area, which is vital for every dental student and dentist. To avoid confusion, the terms and definitions of the Glossary of Prosthodontics5 are used.
    • Fundamentals of occlusion and restorative dentistry. Part II: occlusal contacts, interferences and occlusal considerations in implant patients

      Warreth, Abdulhadi (Irish Dental Assocation (IDA), 2015-10)
      This second part of the two-part article discusses different types of occlusal contacts and their interferences. It also provides a practical guide to what is required to optimise the restorative treatment outcome. Occlusion and its effect on dental implants are also presented. Clinical relevance: Restorative treatment outcome is highly dependent on the occlusion of the restoration when the treatment is complete
    • Fungal infections of humans

      Sullivan, DJ; Moran, GP (Oxford, John Wiley & Sons Ltd, 2011)
      2nd edition
    • Fungal infections of humans.

      Sullivan, D.J.; Moran, G.P.; Coleman, D.C.; Dublin Dental University Hospital (John Wiley & Sons, Ltd, 2005-12)
    • Genetic associations of 115 polymorphisms with cancers of the upper aerodigestive tract across 10 European countries: the ARCAGE project.

      Canova, Cristina; Hashibe, Mia; Simonato, Lorenzo; Nelis, Mari; Metspalu, Andres; Lagiou, Pagona; Trichopoulos, Dimitrios; Ahrens, Wolfgang; Pigeot, Iris; Merletti, Franco; et al. (2009-04-01)
      Cancers of the upper aerodigestive tract (UADT) include malignant tumors of the oral cavity, pharynx, larynx, and esophagus and account for 6.4% of all new cancers in Europe. In the context of a multicenter case-control study conducted in 14 centers within 10 European countries and comprising 1,511 cases and 1,457 controls (ARCAGE study), 115 single nucleotide polymorphisms (SNP) from 62 a priori-selected genes were studied in relation to UADT cancer. We found 11 SNPs that were statistically associated with UADT cancers overall (5.75 expected). Considering the possibility of false-positive results, we focused on SNPs in CYP2A6, MDM2, tumor necrosis factor (TNF), and gene amplified in squamous cell carcinoma 1 (GASC1), for which low P values for trend (P trend<0.01) were observed in the main effects analyses of UADT cancer overall or by subsite. The rare variant of CYP2A6 -47A>C (rs28399433), a phase I metabolism gene, was associated with reduced UADT cancer risk (P trend=0.01). Three SNPs in the MDM2 gene, involved in cell cycle control, were associated with UADT cancer. MDM2 IVS5+1285A>G (rs3730536) showed a strong codominant effect (P trend=0.007). The rare variants of two SNPs in the TNF gene were associated with a decreased risk; for TNF IVS1+123G>A (rs1800610), the P trend was 0.007. Variants in two SNPs of GASC1 were found to be strongly associated with increased UADT cancer risk (for both, P trend=0.008). This study is the largest genetic epidemiologic study on UADT cancers in Europe. Our analysis points to potentially relevant genes in various pathways.
    • Genioglossus fatigue in obstructive sleep apnea.

      McSharry, David; O'Connor, Ciara; McNicholas, Triona; Langran, Simon; O'Sullivan, Michael; Lowery, Madeleine; McNicholas, Walter T; Sleep Research Laboratory, St. Vincent's University Hospital, Dublin, Ireland. dmcsharry@partners.org (2012-08-15)
      Obstructive sleep apnea (OSA) is a prevalent disorder that may cause cardiovascular disease and fatal traffic accidents but the pathophysiology remains incompletely understood. Increased fatigability of the genioglossus (the principal upper airway dilator muscle) might be important in OSA pathophysiology but the existing literature is uncertain. We hypothesized that the genioglossus in OSA subjects would fatigue more than in controls. In 9 OSA subjects and 9 controls during wakefulness we measured maximum voluntary tongue protrusion force (Tpmax). Using surface electromyography arrays we measured the rate of decline in muscle fiber conduction velocity (MFCV) during an isometric fatiguing contraction at 30% Tpmax. The rate of decline in MFCV provides an objective means of quantifying localized muscle fatigue. Linear regression analysis of individual subject data demonstrated a significantly greater decrease in MFCV in OSA subjects compared to control subjects (29.2 ± 20.8% [mean ± SD] versus 11.2 ± 20.8%; p=0.04). These data support increased fatigability of the genioglossus muscle in OSA subjects which may be important in the pathophysiology of OSA.
    • Genome-wide association study of classical Hodgkin lymphoma and Epstein-Barr virus status-defined subgroups.

      Urayama, Kevin Y; Jarrett, Ruth F; Hjalgrim, Henrik; Diepstra, Arjan; Kamatani, Yoichiro; Chabrier, Amelie; Gaborieau, Valerie; Boland, Anne; Nieters, Alexandra; Becker, Nikolaus; et al. (Journal of the National Cancer Institute, 2012-02-08)
      Accumulating evidence suggests that risk factors for classical Hodgkin lymphoma (cHL) differ by tumor Epstein-Barr virus (EBV) status. This potential etiological heterogeneity is not recognized in current disease classification.
    • A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium.

      McKay, James D; Truong, Therese; Gaborieau, Valerie; Chabrier, Amelie; Chuang, Shu-Chun; Byrnes, Graham; Zaridze, David; Shangina, Oxana; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; et al. (2011-03)
      Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p ≤ 5 × 10⁻⁷). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10⁻⁸) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p =2 × 10⁻⁸) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 × 10⁻⁸); rs1229984-ADH1B, p = 7 × 10⁻⁹; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.
    • Genome-wide gene expression profiling and a forward genetic screen show that differential expression of the sodium ion transporter Ena21 contributes to the differential tolerance of Candida albicans and Candida dubliniensis to osmotic stress.

      Enjalbert, Brice; Moran, Gary P; Vaughan, Claire; Yeomans, Tim; Maccallum, Donna M; Quinn, Janet; Coleman, David C; Brown, Alistair J P; Sullivan, Derek J; Aberdeen Fungal Group, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK. (2009-04)
      Candida albicans is more pathogenic than Candida dubliniensis. However, this disparity in virulence is surprising given the high level of sequence conservation and the wide range of phenotypic traits shared by these two species. Increased sensitivity to environmental stresses has been suggested to be a possible contributory factor to the lower virulence of C. dubliniensis. In this study, we investigated, in the first comparison of C. albicans and C. dubliniensis by transcriptional profiling, global gene expression in each species when grown under conditions in which the two species exhibit differential stress tolerance. The profiles revealed similar core responses to stresses in both species, but differences in the amplitude of the general transcriptional responses to thermal, salt and oxidative stress. Differences in the regulation of specific stress genes were observed between the two species. In particular, ENA21, encoding a sodium ion transporter, was strongly induced in C. albicans but not in C. dubliniensis. In addition, ENA21 was identified in a forward genetic screen for C. albicans genomic sequences that increase salt tolerance in C. dubliniensis. Introduction of a single copy of CaENA21 was subsequently shown to be sufficient to confer salt tolerance upon C. dubliniensis.
    • Genome-wide meta-analyses identify multiple loci associated with smoking behavior.

      Department of Genetics, University of North Carolina, Chapel Hill, NC 27710, USA. (2010-05)
      Consistent but indirect evidence has implicated genetic factors in smoking behavior. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], beta = 1.03, standard error (s.e.) = 0.053, P = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], beta = 0.367, s.e. = 0.059, P = 5.7 x 10(-10); and rs1028936[A], beta = 0.446, s.e. = 0.074, P = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], beta = 0.333, s.e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.
    • Global Transcriptome Sequencing Identifies Chlamydospore Specific Markers in Candida albicans and Candida dubliniensis

      Palige, Katja; Linde, Jörg; Martin, Ronny; Böttcher, Bettina; Citiulo, Francesco; Sullivan, Derek J.; Weber, Johann; Staib, Claudia; Rupp, Steffen; Hube, Bernhard; et al. (2013-04-15)
      Candida albicans and Candida dubliniensis are pathogenic fungi that are highly related but differ in virulence and in some phenotypic traits. During in vitro growth on certain nutrient-poor media, C. albicans and C. dubliniensis are the only yeast species which are able to produce chlamydospores, large thick-walled cells of unknown function. Interestingly, only C. dubliniensis forms pseudohyphae with abundant chlamydospores when grown on Staib medium, while C. albicans grows exclusively as a budding yeast. In order to further our understanding of chlamydospore development and assembly, we compared the global transcriptional profile of both species during growth in liquid Staib medium by RNA sequencing. We also included a C. albicans mutant in our study which lacks the morphogenetic transcriptional repressor Nrg1. This strain, which is characterized by its constitutive pseudohyphal growth, specifically produces masses of chlamydospores in Staib medium, similar to C. dubliniensis. This comparative approach identified a set of putatively chlamydospore-related genes. Two of the homologous C. albicans and C. dubliniensis genes (CSP1 and CSP2) which were most strongly upregulated during chlamydospore development were analysed in more detail. By use of the green fluorescent protein as a reporter, the encoded putative cell wall related proteins were found to exclusively localize to C. albicans and C. dubliniensis chlamydospores. Our findings uncover the first chlamydospore specific markers in Candida species and provide novel insights in the complex morphogenetic development of these important fungal pathogens.
    • Good science

      Journal of the Irish Dental Association (Journal of the Irish Dental Association, 2009-02)
    • Guidelines for Reporting Novel mecA Gene Homologues

      Ito, T.; Hiramatsu, K.; Tomasz, A.; de Lencastre, H.; Perreten, V.; Holden, M. T. G.; Coleman, D. C.; Goering, R.; Giffard, P. M.; Skov, R. L.; et al. (Antimicrobial Agents and Chemotherapy, 2012-10)