This collection contains clinical research and documentation from a variety of Irish health organisations.

Recent Submissions

  • LINGO1 is a regulatory subunit of large conductance, Ca-activated potassium channels.

    Dudem, Srikanth; Large, Roddy J; Kulkarni, Shruti; McClafferty, Heather; Tikhonova, Irina G; Sergeant, Gerard P; Thornbury, Keith D; Shipston, Michael J; Perrino, Brian A; Hollywood, Mark A (2020-01-13)
    LINGO1 is a transmembrane protein that is up-regulated in the cerebellum of patients with Parkinson's disease (PD) and Essential Tremor (ET). Patients with additional copies of the LINGO1 gene also present with tremor. Pharmacological or genetic ablation of large conductance Ca2+-activated K+ (BK) channels also result in tremor and motor disorders. We hypothesized that LINGO1 is a regulatory BK channel subunit. We show that 1) LINGO1 coimmunoprecipitated with BK channels in human brain, 2) coexpression of LINGO1 and BK channels resulted in rapidly inactivating BK currents, and 3) LINGO1 reduced the membrane surface expression of BK channels. These results suggest that LINGO1 is a regulator of BK channels, which causes a "functional knockdown" of these currents and may contribute to the tremor associated with increased LINGO1 levels.
  • Exposure of to Atorvastatin Leads to Altered Membrane Permeability and Induction of an Oxidative Stress Response.

    Ajdidi, Ahmad; Sheehan, Gerard; Kavanagh, Kevin (2020-03-26)
    Aspergillus fumigatus is a serious cause of disease in immune-deficient patients and in those with pulmonary malfunction (e.g., cystic fibrosis (CF), asthma). Atorvastatin is a member of the statin drug family, which are the main therapeutic agents used to decrease high serum cholesterol levels by inhibiting (HMG-CoA) reductase enzyme. The aim of the work presented here was to analyse the antifungal activity of atorvastatin and assess its effect on the virulence of A. fumigatus. Atorvastatin demonstrated strong antifungal activity and reduced the growth and viability of A. fumigatus. Exposure of A. fumigatus to atorvastatin led to a reduction in ergosterol content and increased membrane permeability, as evidenced by the release of protein, amino acids and gliotoxin. Proteomic analysis revealed an increased abundance of proteins associated with an oxidative stress response, such as the glutathione s-transferase family protein (+8.43-fold), heat shock protein Hsp30/Hsp42 (+2.02-fold) and 5-demethoxyubiquinone hydroxylase, mitochondrial (+1.73-fold), as well as secondary metabolites such as isocyanide synthase A icsA (+8.52-fold) and non-ribosomal peptide synthetase fmpE (+3.06-fold). The results presented here indicate that atorvastatin has strong antifungal properties and may have potential application in the treatment of A. fumigatus infections alone or in combination with existing antifungal agents.
  • Bone-on-Bone Anatomic Patellar Tendon Graft Anterior Cruciate Ligament Reconstruction: A Reproducible Technique Combining Press-Fit and Extracortical Fixation.

    Brandl, Georg; Ostermann, Roman Christian; Pauzenberger, Leo; Lobo, Christopher; Feichtinger, Xaver (2020-01-07)
  • Shielding and Beyond: The Roles of Glycans in SARS-CoV-2 Spike Protein.

    Casalino, Lorenzo; Gaieb, Zied; Goldsmith, Jory A; Hjorth, Christy K; Dommer, Abigail C; Harbison, Aoife M; Fogarty, Carl A; Barros, Emilia P; Taylor, Bryn C; McLellan, Jason S; et al. (2020-06-11)
  • increases the pathogenicity of during polymicrobial infection of larvae.

    Sheehan, Gerard; Tully, Laura; Kavanagh, Kevin A (2020-02-18)
    This study detailed the responses of Galleria mellonella larvae to disseminated infection caused by co-infection with Candida albicans and Staphylococcus aureus. Doses of C. albicans (1×105 larva-1) and S. aureus (1×104 larva-1) were non-lethal in mono-infection but when combined significantly (P<0.05) reduced larval survival at 24, 48 and 72 h relative to larvae receiving S. aureus (2×104 larva-1) alone. Co-infected larvae displayed a significantly higher density of S. aureus larva-1 compared to larvae infected solely with S. aureus. Co-infection resulted in dissemination throughout the host and the appearance of large nodules. Co-infection of larvae with C. albicans and S. aureus (2×104 larva-1) resulted in an increase in the density of circulating haemocytes compared to that in larvae infected with only S. aureus. Proteomic analysis of co-infected larval haemolymph revealed increased abundance of proteins associated with immune responses to bacterial and fungal infection such as cecropin-A (+45.4-fold), recognition proteins [e.g. peptidoglycan-recognition protein LB (+14-fold)] and proteins associated with nodule formation [e.g. Hdd11 (+33.3-fold)]. A range of proteins were also decreased in abundance following co-infection, including apolipophorin (-62.4-fold), alpha-esterase 45 (-7.7-fold) and serine proteinase (-6.2-fold). Co-infection of larvae resulted in enhanced proliferation of S. aureus compared to mono-infection and an immune response showing many similarities to the innate immune response of mammals to infection. The utility of G. mellonella larvae for studying polymicrobial infection is highlighted.
  • Comprehensive biophysical and functional study of ziv-aflibercept: characterization and forced degradation.

    Hermosilla, Jesús; Pérez-Robles, Raquel; Salmerón-García, Antonio; Casares, Salvador; Cabeza, Jose; Bones, Jonathan; Navas, Natalia (2020-02-14)
  • Search Strategy for Evidence Reviews in COVID-19

    National Centre for Pharmacoeconomics; COVID-19 Evidence Review Group (ERG) (2020-05-01)
  • Rapid Evidence Review: Tocilizumab in the management of patients who have severe COVID-19 infection with suspected hyperinflammation. [v3.0]

    National Centre for Pharmacoeconomics; COVID-19 Evidence Review Group for Medicines (National Centre for Pharmacoeconomics, 2020-05-20)
  • Rapid Evidence Review: Clinical evidence for hydroxychloroquine and azithromycin combination therapy for COVID-19 [v3.0]

    National Centre for Pharmacoeconomics; COVID-19 Evidence Review Group for Medicines (National Centre for Pharmacoeconomics, 2020-04-17)
  • Rapid Evidence Review: Clinical evidence for the use of intravenous immunoglobulin in the treatment of COVID-19 [v2.0]

    National Centre for Pharmacoeconomics; COVID-19 Evidence Review Group for Medicines (National Centre for Pharmacoeconomics, 2020-05-14)
  • Rapid Evidence Review: Clinical evidence on the use of pharmacological prophylactic therapy in healthcare workers or contacts of cases of COVID-19 [v6.0]

    National Centre for Pharmacoeconomics; COVID-19 Evidence Review Group for Medicines (Health Information and Quality Authority (HIQA), 2020-06-29)
  • Clinical evidence for the use of antivirals in the treatment of COVID-19 [v10.0]

    COVID-19 Evidence Review Group; National Centre for Pharmacoeconomics; Medicines Management Programme; Health Service Executive (Health Service Executive, 2020-06-26)
  • Rapid Evidence Review Clinical evidence for thromboprophylaxis in the management of COVID-19 [v1.0]

    National Centre for Pharmacoeconomics; COVID-19 Evidence Review Group for Medicines (National Centre for Pharmacoeconomics, 2020-05-07)