Recent Submissions

  • Economic burden of maternal morbidity - A systematic review of cost-of-illness studies.

    Moran, Patrick S; Wuytack, Francesca; Turner, Michael; Normand, Charles; Brown, Stephanie; Begley, Cecily; Daly, Deirdre (2020-01-16)
  • Pharmacological Activation of Pyruvate Kinase M2 Inhibits CD4 T Cell Pathogenicity and Suppresses Autoimmunity.

    Angiari, Stefano; Runtsch, Marah C; Sutton, Caroline E; Palsson-McDermott, Eva M; Kelly, Beth; Rana, Nisha; Kane, Harry; Papadopoulou, Gina; Pearce, Erika L; Mills, Kingston H G; et al. (2019-11-21)
    Pyruvate kinase (PK) catalyzes the conversion of phosphoenolpyruvate to pyruvate during glycolysis. The PK isoform PKM2 has additional roles in regulation of gene transcription and protein phosphorylation. PKM2 has been shown to control macrophage metabolic remodeling in inflammation, but its role in T cell biology is poorly understood. Here, we report PKM2 upregulation, phosphorylation, and nuclear accumulation in murine and human CD4+ T cells following activation in vitro. Treatment of T cells with TEPP-46, an allosteric activator that induces PKM2 tetramerization and blocks its nuclear translocation, strongly reduces their activation, proliferation, and cytokine production by inhibiting essential signaling pathways and thus preventing the engagement of glycolysis. TEPP-46 limits the development of both T helper 17 (Th17) and Th1 cells in vitro and ameliorates experimental autoimmune encephalomyelitis (EAE) in vivo. Overall, our results suggest that pharmacological targeting of PKM2 may represent a valuable therapeutic approach in T cell-mediated inflammation and autoimmunity.
  • Structures of lipoprotein signal peptidase II from Staphylococcus aureus complexed with antibiotics globomycin and myxovirescin.

    Olatunji, Samir; Yu, Xiaoxiao; Bailey, Jonathan; Huang, Chia-Ying; Zapotoczna, Marta; Bowen, Katherine; Remškar, Maja; Müller, Rolf; Scanlan, Eoin M; Geoghegan, Joan A; et al. (2020-01-09)
  • Syncope, Fear of Falling and Quality of Life Among Older Adults: Findings From the Irish Longitudinal Study on Aging (TILDA).

    McCarthy, Kevin; Ward, Mark; Romero Ortuño, Román; Kenny, Rose Anne (2020-02-07)
    Objective: Syncope is a prevalent condition that has a marked impact on quality of life. We examined the association between syncope and quality of life (QoL) and whether this association was explained by fear of falling (FoF). Methods: We examined data from Wave 3 of The Irish Longitudinal Study on Aging (TILDA), of adults aged ≥50 years (n = 4,946) who were asked to report syncope and who completed the CASP-12 QoL instrument. Analyses were stratified by age and gender. Results: Over 20% of participants reported having a previous syncopal episode, while 8% reported a faint, blackout or unexplained fall in the last year. QoL scores decreased as the burden of syncope increased: linear regression models adjusted for covariates showed that those having had two or more syncopal episodes in the last year reported a significantly lower CASP-12 score compared to those with none (p = 0.011). FoF partially mediated the association between syncope and QoL, particularly among younger participants. Conclusions: Syncope is a common condition among older adults that has a deleterious effect on QoL, with ≥2 recent syncopal episodes having a particularly adverse impact on QoL. FoF is a potential pathway which may both explain this association and allow therapeutic interventions by health practitioners.
  • Perceptions of eHealth-Enabled Physical Activity Interventions Among Cancer Survivors: Mixed Methods Study.

    Haberlin, Ciaran; O' Donnell, Dearbhaile M; Moran, Jonathan; Broderick, Julie (2020-04-28)
  • Personal information and public health: Design tensions in sharing and monitoring wellbeing in pregnancy.

    Doherty, Kevin; Barry, Marguerite; Belisario, José Marcano; Morrison, Cecily; Car, Josip; Doherty, Gavin (2020-03)
  • Modeling and Rescue of RP2 Retinitis Pigmentosa Using iPSC-Derived Retinal Organoids.

    Lane, Amelia; Jovanovic, Katarina; Shortall, Ciara; Ottaviani, Daniele; Panes, Anna Brugulat; Schwarz, Nele; Guarascio, Rosellina; Hayes, Matthew J; Palfi, Arpad; Chadderton, Naomi; et al. (2020-06-11)
  • Advanced late-onset retinitis pigmentosa with dominant-acting D477G RPE65 mutation is responsive to oral synthetic retinoid therapy.

    Kenna, Paul F; Humphries, Marian M; Kiang, Anna-Sophia; Brabet, Philippe; Guillou, Laurent; Ozaki, Ema; Campbell, Matthew; Farrar, G Jane; Koenekoop, Robert; Humphries, Pete (2020-05-05)
    No therapeutic interventions are currently available for autosomal dominant retinitis pigmentosa (adRP). An RPE65 Asp477Gly transition associates with late-onset adRP, reduced RPE65 enzymatic activity being one feature associated with this dominant variant. Our objective: to assess whether in a proof-of-concept study, oral synthetic 9 cis-retinyl acetate therapy improves vision in such advanced disease.
  • Are payment methods for prescription drugs associated with polypharmacy in older adults in Ireland? Evidence from the TILDA cohort study.

    Varley, Aine; Cullinan, John; 1Department of Pharmacology and Therapeutics, Trinity College Dublin, Dublin, Ireland varleyai@tcd.ie. 2Discipline of Economics, National University of Ireland Galway, Galway, Ireland. (2020-10-01)
  • High Content Imaging of Barrett's-Associated High-Grade Dysplasia Cells After siRNA Library Screening Reveals Acid-Responsive Regulators of Cellular Transitions.

    Phipps, Sinead M; Garry, Catherine E; Kamal, Sepehr; Johnson, James D; Gilmer, John; Long, Aideen; Kelleher, Dermot; Duggan, Shane P (2020-05-13)
  • Evaluating the neurophysiological evidence for predictive processing as a model of perception.

    Walsh, Kevin S; McGovern, David P; Clark, Andy; O'Connell, Redmond G (2020-03-08)
  • Connectome-Based Propagation Model in Amyotrophic Lateral Sclerosis.

    Meier, Jil M; van der Burgh, Hannelore K; Nitert, Abram D; Bede, Peter; de Lange, Siemon C; Hardiman, Orla; van den Berg, Leonard H; van den Heuvel, Martijn P (2020-03-11)
  • The exposome in atopic dermatitis.

    Stefanovic, Nicholas; Flohr, Carsten; Irvine, Alan D (2019-08-19)
  • Stakeholder perspectives of Community Mental Health Forums: a qualitative study in Sierra Leone.

    Adams, Ben; Vallières, Frédérique; Duncan, Joshua Abioseh; Higgins, Agnes; Eaton, Julian (2020-07-10)
    Results identified three themes, Traditional Beliefs and Culture; Health System; and Inclusive Approaches as affecting the implementation of CMHFs in their districts. Participants further perceived that their participation in the Community Mental Health Forums resulted in changes taking place across the themes of Awareness and beliefs, Behaviours towards people experiencing psychological distress, and as leading to greater Collaboration and cooperation between formal and informal mental health practitioners.
  • Interventions for oropharyngeal dysphagia in acute and critical care: a systematic review and meta-analysis.

    Duncan, Sallyanne; McAuley, Daniel F; Walshe, Margaret; McGaughey, Jennifer; Anand, Rohan; Fallis, Richard; Blackwood, Bronagh (2020-06-08)
    We identified 22 studies (19 stroke, 2 intensive care stroke and 1 general intensive care) testing 9 interventions and representing 1700 patients. Swallowing treatment showed no evidence of a difference in the time to return to oral intake (n = 33, MD (days) - 4.5, 95% CI - 10.6 to 1.6, 1 study, P = 0.15) (very low certainty) or in aspiration following treatment (n = 113, RR 0.79, 95% CI 0.44 to 1.45, 4 studies, I2 = 0%, P = 0.45) (low certainty). Swallowing treatment showed evidence of a reduced risk of pneumonia (n = 719, RR 0.71, 95% CI 0.56 to 0.89, 8 studies, I2 = 15%, P = 0.004) (low certainty) but no evidence of a difference in swallowing quality of life scores (n = 239, MD - 11.38, 95% CI - 23.83 to 1.08, I 2 = 78%, P = 0.07) (very low certainty).
  • The effectiveness and characteristics of pregnancy yoga interventions: a systematic review protocol.

    Corrigan, Lisa; Eustace-Cook, Jessica; Moran, Patrick; Daly, Deirdre (2020-01-08)
    Background: The purpose of this review is to systematically examine the reported clinical effectiveness of pregnancy yoga.  The review will use the FITT (frequency, intensity, time/duration and type) principle of physical activity to characterise the different types of yoga interventions that have been evaluated in the included studies.  Studies will be categorised as effectiveness or efficacy studies and this continuum of efficacy versus effectiveness will be incorporated into the full review.  Methods/design: The following electronic databases will be searched using a detailed search strategy: MEDLINE, PsycINFO, EMBASE, CINAHL, WHOLiS, AMED, ScieLo, ASSIA and Web of Science. Randomised control trials and quasi-experimental studies examining pregnancy yoga and reporting on effect will be included. Titles, abstracts and full articles will be screened by two investigators independently to identify eligible studies.  The Cochrane Collaboration's Risk of Bias Assessment tool will be used to assess study quality.  Quality of the evidence will be evaluated using the GRADE criteria. A standardised data extraction form will be used to extract data. Effect sizes will be estimated using mean differences for continuous outcomes, and relative risks for dichotomous outcome. Where possible, pooling of effect estimates will be done using a random effect model.  The outcomes of interest are quality of life, stress, anxiety, depression, mode of birth, labour duration and pain management in labour. Discussion: This review will synthesise the best available evidence on the effectiveness of yoga during pregnancy and provide valuable high-quality information for clinicians and health policymakers. Findings will be disseminated through publication in a peer-reviewed journal and presentation at relevant conference proceedings. The review will make recommendations for the appropriate volume, intensity and type of pregnancy yoga for maximum effect and may have implications for policy and practice relating to pregnancy yoga as an intervention.   Registration: PROSPERO, CRD42019119916.  Registered on 11th January 2019.
  • Internet-Delivered Cognitive Behavior Therapy as a Prequel to Face-To-Face Therapy for Depression and Anxiety: A Naturalistic Observation.

    Duffy, Daniel; Enrique, Angel; Connell, Sarah; Connolly, Conor; Richards, Derek (2020-01-09)
    Background: The UK's Improving Access to Psychological Therapies (IAPT) program is a stepped-care model treating individuals with depression and anxiety disorders. Internet-delivered cognitive behavioral therapy (iCBT) is routinely offered to individuals with mild to moderate symptoms, but its applicability to individuals with severe clinical symptoms and requiring a high-intensity intervention is relatively unknown. The current study sought to investigate the potential impacts of using iCBT as a prequel for patients requiring high-intensity treatment (HIT; face-to-face) for depression and anxiety in IAPT. Methods: The study utilized an open study design. One hundred and twenty-four participants who were on a waiting list for high-intensity, face-to-face psychological treatment were offered iCBT. Psychometric data on symptoms of depression, anxiety, and functioning were collected from participants before starting and on finishing iCBT and at the point of service exit. Therapeutic alliance data were collected from patients and clinicians during treatment. Patient pathway data, such as number of treatment sessions and time in treatment, was also collected and incorporated into the analysis. Results: Significant reductions across primary outcome measures of depression and anxiety, as well as improved functioning, were observed from baseline to iCBT treatment exit, and from iCBT exit to service exit. Analysis of the therapeutic alliance data for patients and clinicians illustrated differences in outcome for those who dropped out and those who completed treatment. Discussion: This study illustrates the potential for using iCBT as a prequel to high-intensity therapy for depression and anxiety disorders and is the first of its kind to do so within IAPT stepped care. The results show that iCBT is a valuable option reducing waiting times and enhancing clinical efficiency. The study contributes to the well-established evidence on online psychological treatments worldwide, but further clinical and service development research is necessary to scale these treatments appropriately.

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