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

Recent Submissions

  • Rapid Evidence Review: Tocilizumab in the management of patients who have severe COVID-19 infection with suspected hyperinflammation. [v6.0]

    National Centre for Pharmacoeconomics; COVID-19 Evidence Review Group for Medicines (National Centre for Pharmacoeconomics, 2021-02-25)
  • High Throughput Sequencing for the Detection and Characterization of RNA Viruses.

    Fitzpatrick, Amy H; Rupnik, Agnieszka; O'Shea, Helen; Crispie, Fiona; Keaveney, Sinéad; Cotter, Paul (2021-02-22)
  • Reliability and Validity of Clinically Accessible Smart Glove Technologies to Measure Joint Range of Motion.

    Henderson, Jeffrey; Condell, Joan; Connolly, James; Kelly, Daniel; Curran, Kevin (2021-02-24)
  • Review of Wearable Sensor-Based Health Monitoring Glove Devices for Rheumatoid Arthritis.

    Henderson, Jeffrey; Condell, Joan; Connolly, James; Kelly, Daniel; Curran, Kevin (2021-02-24)
  • Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity.

    Thomson, Emma C; Rosen, Laura E; Shepherd, James G; Spreafico, Roberto; da Silva Filipe, Ana; Wojcechowskyj, Jason A; Davis, Chris; Piccoli, Luca; Pascall, David J; Dillen, Josh; et al. (2021-01-28)
  • Arthroscopic Correction of Sports-Related Femoroacetabular Impingement in Competitive Athletes: 2-Year Clinical Outcome and Predictors for Achieving Minimal Clinically Important Difference.

    Mullins, Karen; Filan, David; Carton, Patrick (2021-03-04)
    At 2-year follow-up, statistically significant improvements were observed for all PROMs (P < .001 for all), and 84% of athletes continued to play sport. Higher preoperative PROM scores reduced the likelihood of achieving MCID; however, returning to play was the strongest predictor of reaching MCID in this athletic cohort. Using absolute score change (mean change or distribution method) to calculate MCID was less accurate owing to ceiling effects and dependence on preoperative PROM scores.
  • Characterising the efficacy and bioavailability of bioactive peptides identified for attenuating muscle atrophy within a -derived functional ingredient.

    Corrochano, Alberto R; Cal, Roi; Kennedy, Kathy; Wall, Audrey; Murphy, Niall; Trajkovic, Sanja; O'Callaghan, Sean; Adelfio, Alessandro; Khaldi, Nora (2021-04-03)
    Characterising key components within functional ingredients as well as assessing efficacy and bioavailability is an important step in validating nutritional interventions. Machine learning can assess large and complex data sets, such as proteomic data from plants sources, and so offers a prime opportunity to predict key bioactive components within a larger matrix. Using machine learning, we identified two potentially bioactive peptides within a Vicia faba derived hydrolysate, NPN_1, an ingredient which was previously identified for preventing muscle loss in a murine disuse model. We investigated the predicted efficacy of these peptides in vitro and observed that HLPSYSPSPQ and TIKIPAGT were capable of increasing protein synthesis and reducing TNF-α secretion, respectively. Following confirmation of efficacy, we assessed bioavailability and stability of these predicted peptides and found that as part of NPN_1, both HLPSYSPSPQ and TIKIPAGT survived upper gut digestion, were transported across the intestinal barrier and exhibited notable stability in human plasma. This work is a first step in utilising machine learning to untangle the complex nature of functional ingredients to predict active components, followed by subsequent assessment of their efficacy, bioavailability and human plasma stability in an effort to assist in the characterisation of nutritional interventions.
  • Systematic review and network meta-analysis of the efficacy of existing treatments for patients with recurrent glioblastoma.

    Schritz, Anna; Aouali, Nassera; Fischer, Aurélie; Dessenne, Coralie; Adams, Roisin; Berchem, Guy; Huiart, Laetitia; Schmitz, Susanne (2021-04-09)
  • Silver(I) and Copper(II) Complexes of 1,10-Phenanthroline-5,6-Dione Against : A Focus on the Interaction With Human Macrophages and Larvae.

    Granato, Marcela Q; Mello, Thaís P; Nascimento, Renata S; Pereira, Marcos D; Rosa, Thabatta L S A; Pessolani, Maria C V; McCann, Malachy; Devereux, Michael; Branquinha, Marta H; Santos, André L S; et al. (2021-04-27)
    Phialophora verrucosa is a dematiaceous fungus that causes mainly chromoblastomycosis, but also disseminated infections such as phaeohyphomycosis and mycetoma. These diseases are extremely hard to treat and often refractory to current antifungal therapies. In this work, we have evaluated the effect of 1,10-phenanthroline-5,6-dione (phendione) and its metal-based complexes, [Ag (phendione)2]ClO4 and [Cu(phendione)3](ClO4)2.4H2O, against P. verrucosa, focusing on (i) conidial viability when combined with amphotericin B (AmB); (ii) biofilm formation and disarticulation events; (iii) in vitro interaction with human macrophages; and (iv) in vivo infection of Galleria mellonella larvae. The combination of AmB with each of the test compounds promoted the additive inhibition of P. verrucosa growth, as judged by the checkerboard assay. During the biofilm formation process over polystyrene surface, sub-minimum inhibitory concentrations (MIC) of phendione and its silver(I) and copper(II) complexes were able to reduce biomass and extracellular matrix production. Moreover, a mature biofilm treated with high concentrations of the test compounds diminished biofilm viability in a concentration-dependent manner. Pre-treatment of conidial cells with the test compounds did not alter the percentage of infected THP-1 macrophages; however, [Ag(phendione)2]ClO4 caused a significant reduction in the number of intracellular fungal cells compared to the untreated system. In addition, the killing process was significantly enhanced by post-treatment of infected macrophages with the test compounds. P. verrucosa induced a typically cell density-dependent effect on G. mellonella larvae death after 7 days of infection. Interestingly, exposure to the silver(I) complex protected the larvae from P. verrucosa infection. Collectively, the results corroborate the promising therapeutic potential of phendione-based drugs against fungal infections, including those caused by P. verrucosa.
  • Biocidal Resistance in Clinically Relevant Microbial Species: A Major Public Health Risk.

    Meade, Elaine; Slattery, Mark Anthony; Garvey, Mary (2021-05-14)
    Antimicrobial resistance is one of the greatest dangers to public health of the 21st century, threatening the treatment and prevention of infectious diseases globally. Disinfection, the elimination of microbial species via the application of biocidal chemicals, is essential to control infectious diseases and safeguard animal and human health. In an era of antimicrobial resistance and emerging disease, the effective application of biocidal control measures is vital to protect public health. The COVID-19 pandemic is an example of the increasing demand for effective biocidal solutions to reduce and eliminate disease transmission. However, there is increasing recognition into the relationship between biocide use and the proliferation of Antimicrobial Resistance species, particularly multidrug-resistant pathogens. The One Health approach and WHO action plan to combat AMR require active surveillance and monitoring of AMR species; however, biocidal resistance is often overlooked. ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens and numerous fungal species have demonstrated drug and biocidal resistance where increased patient mortality is a risk. Currently, there is a lack of information on the impact of biocide application on environmental habitats and ecosystems. Undoubtedly, the excessive application of disinfectants and AMR will merge to result in secondary disasters relating to soil infertility, loss of biodiversity and destruction of ecosystems.
  • The promise and perils of Unit 731 data to advance COVID-19 research.

    Su, Zhaohui; McDonnell, Dean; Cheshmehzangi, Ali; Abbas, Jaffar; Li, Xiaoshan; Cai, Yuyang (2021-05)
  • Modulates Immunity against SARS-CoV-2 in Respiratory Epithelial Cells.

    Islam, Md Aminul; Albarracin, Leonardo; Melnikov, Vyacheslav; Andrade, Bruno G N; Cuadrat, Rafael R C; Kitazawa, Haruki; Villena, Julio (2021-05-21)
    In a previous work, we demonstrated that nasally administered Dolosigranulum pigrum 040417 beneficially modulated the respiratory innate immune response triggered by the activation of Toll-like receptor 3 (TLR3) and improved protection against Respiratory Syncytial Virus (RSV) in mice. In this work, we aimed to evaluate the immunomodulatory effects of D. pigrum 040417 in human respiratory epithelial cells and the potential ability of this immunobiotic bacterium to increase the protection against Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The respiratory commensal bacterium D. pigrum 040417 differentially modulated the production of IFN-β, IL-6, CXCL8, CCL5 and CXCL10 in the culture supernatants of Calu-3 cells stimulated with poly(I:C) or challenged with SARS-CoV-2. The differential cytokine profile induced by the 040417 strain was associated with a significant reduction in viral replication and cellular damage after coronavirus infection. Of note, D. pigrum 030918 was not able to modify the resistance of Calu-3 cells to SARS-CoV-2 infection, indicating a strain-specific immunomodulatory effect for respiratory commensal bacteria. The findings of this work improve our understanding of the immunological mechanisms involved in the modulation of respiratory immunity induced by respiratory commensal bacteria, by demonstrating their specific effect on respiratory epithelial cells. In addition, the results suggest that particular strains such as D. pigrum 040417 could be used as a promising alternative for combating SARS-CoV-2 and reducing the severity of COVID-19.
  • Microfluidics in Haemostasis: A Review.

    Jigar Panchal, Heta; Kent, Nigel J; Knox, Andrew J S; Harris, Leanne F (2020-02-14)
  • 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.
  • 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)
  • 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.
  • 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.

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