CoMH Research Conference 2024 Book of Abstracts

Health

Thursday 12th December 2024 Western Gateway Building, University College Cork

College of Medicine and Health Research Conference

Futures 2024: Transforming Tomorrow’s Health

Welcome Dear Friends and Colleagues, Welcome to the College of Medicine and Health Annual Research Conference. This year’s theme, "Futures 2024: Transforming Tomorrow’s Health" highlights our commitment to advancing health and wellbeing through innovation and collaboration. It reflects the College’s ongoing work to establish an Academic Health Sciences System (AHSS) in the South West region. This integrated partnership between UCC and our healthcare system will ensure that research and innovation directly benefit patients. The work presented hereby all attendees is central to achieving this vision.

Today’s conference has garnered significant interest, with 300 registrations and over 150 abstracts submitted by researchers working in diverse areas, including but not limited to Future Medicines, Future Ageing & Brain Science, Children, Food, Microbiome & Health, and Health Services Research. The conference features talks from four distinguished invited speakers and includes a selection of oral presentations. These presentations are divided into two dynamic formats: eight-minute ‘Latest Advances’ talks and three-minute ‘Elevator Pitches,’ all chosen from the submitted abstracts. It is truly inspiring to witness how this research is addressing critical societal needs and global health challenges to transform tomorrow’s health.

A day like today would not be possible without the immense support and dedication of many individuals.

We extend our sincere thanks to Dr Susan Rafferty-McArdle, Jill O’Callaghan, Laoise Power and Caroline Seacy from the College of Medicine & Health Office for their exceptional efforts, particularly in organizing the abstracts and poster session. We are also deeply grateful to our Schools, School Managers and staff for their invaluable contributions, Nessa McArdle (TY student) and Jacinta Moore for logo design, as well as the members of the College of Medicine and Health Research and Innovation Committee for their roles in the abstract process, chairing sessions, and serving on judging panels. Finally, a huge thank you to everyone involved in making today’s event a success - your efforts, though too numerous to name individually, are greatly appreciated.

While today is a day to celebrate the diverse research and innovation landscape of the College, we must do so without someone who was instrumental to it. We were all deeply shocked and saddened to learn of Dr Ashleigh Byrne’s untimely passing earlier this year. Her many contributions are impossible to fully capture, but perhaps the most fitting tribute is to acknowledge the kind, selfless, and tireless way she supported and celebrated the achievements of others. Ashleigh was a wonderful person who leaves an enduring legacy of kindness, professionalism, dedication, and inspiration.

In keeping with that spirit of inspiration, we hope you enjoy the conference and take full advantage of this opportunity to forge new connections and explore new possibilities for collaboration.

Best wishes, Professor Helen Whelton Head of the College of Medicine & Health, College of Medicine & Health, UCC & Chief Academic Officer to the HSE South West Region

Professor Gerard O’Keeffe Vice Head for Research & Innovation, College of Medicine & Health, UCC

Table of Contents Programme of Events .............................................................................................................................. 1 Invited Speakers’ Biographies ................................................................................................................. 4 Oral Presentations................................................................................................................................... 6 Session 1: Latest Advances.................................................................................................................. 6 Session 1: Elevator Pitches ................................................................................................................ 10 Session 2: Latest Advances................................................................................................................ 14 Session 2: Elevator Pitches ................................................................................................................ 18 Session 3: Latest Advances................................................................................................................ 22 Session 3: Elevator Pitches ................................................................................................................ 26 Poster Presentations ......................................................................................................................... 29 Poster Numbers and Room Locations ................................................................................................. 145

Programme of Events 08:00 – 08:50 09:00 – 09:10

Arrival and poster setup Professor Helen Whelton, Head of College of Medicine and Health and Chief Academic Officer to the HSE South West Region

09:10 – 10:30

Session 1 CoMH Futures Co-Chaired by Prof. Yvonne Nolan and Dr Piotr Kowalski

09:10 – 09:35

Invited talk by Professor Ken O’Halloran Department of Physiology, UCC.

Adaptive homeostasis in the lab, the clinic, and our institution!

09:35 – 10:15

Latest Advances 1 (8-minute research talks with 2 minutes of questions) Prof. Sarah Kittel-Schneider 1

Department of Psychiatry and Neurobehavioural Science, 2 Cork University Hospital, 3 APC Microbiome Ireland, University College Cork, Cork, Ireland.

Revealing pathomechanims in neurodevelopmental and mental disorders by using human derived cellular models.

Dr Cristina Rosell-Cardona APC Microbiome Ireland, University College Cork, Cork, Ireland

Acute stress, microbial metabolites, and the microbiota-gut-brain axis: focus on microbial regulation of barrier function and hippocampal plasticity.

Dr Edward Fahy Dental School and Hospital, College of Medicine & Health, UCC.

Spectroscopy of oral potentially malignant disorders – towards a protocol for its use.

Dr Michelle O’Driscoll 1

National Suicide Research Foundation and 2School of Pharmacy, UCC.

The implementation and evaluation of a suicide prevention module for undergraduate health and social care students.

10:15 – 10:30

Elevator Pitches 1 (3-minute elevator pitch style talks, 1 question) Minoo Ashoori 1

Department of Physiology and 2INFANT Research Centre

PREMI-NIRS: advanced NIRS signal analysis and machine learning for extremely preterm infants.

Melanie Depret 1

Department of Anatomy and Neuroscience and 2APC Microbiome Ireland

Functional mapping of brain pathways involved in the gut microbial modulation of social behaviour.

James V. Harte 1

School of Biochemistry and Cell Biology and 2Department of Haematology, CUH.

SARS_COV-2-induced syncytia have enhanced procoagulant activity.

Miguel Ramôa School of Pharmacy, College of Medicine & Health, UCC.

Development of Polymeric Nanoparticles for Oral Delivery of RNA as a Treatment for Ileal Crohn’s Disease.

10:30 – 12:00 Coffee Break, Poster Viewing and Networking (Poster session from 10:50 - 11:50) Page | 1

12:10 – 13:30

Session 2 CoMH Futures Co-Chaired by Prof. Nicola Cornally and Prof. John Browne

12:10 – 12:35

Invited talk by Professor Ella Arensman 1

School of Public Health and 2National Suicide Research Foundation.

Public Health approaches to preventing suicide and self-harm: Progress and challenges.

12:35 – 13:15

Latest Advances 2 (8-minute research talks with 2 minutes of questions) Dr Emmy Racine School of Public Health, College of Medicine and Health, UCC.

Co-design, co-development and co-delivery of a new Introduction to Patient and Public Involvement (PPI) in Health and Social Care Research 5 ECTs Postgraduate Module.

Dr Elaine Lehane School of Nursing & Midwifery, College of Medicine and Health, UCC.

Using innovative approaches to translational research in enhancing breastfeeding across healthcare settings.

Ms Eibhlín Looney School of Public Health, College of Medicine and Health, UCC.

Perinatal stress & anxiety in Ireland: Sources, experiences, and support needs.

Dr Salvatore Tedesco Tyndall National Institute

Wearable Enabled Symptom Assessment Algorithm (WESAA) - a novel remote monitoring solution for people with Parkinson's disease.

13:15 – 13:30

Elevator Pitches 2 (3-minute elevator pitch style talks, 1 question) Ruth Daunt School of Medicine, College of Medicine and Health, UCC.

A Prospective Observational Study on the Prevalence of Prescribing Cascades In Older Adults Admitted to Hospital.

Rehab Elhiny School of Pharmacy, College of Medicine and Health, UCC.

Cardiovascular risk control in community-based Irish adults with dyslipidemia.

Maria Carey 1

CancerResearch @UCC, College of Medicine and Health, UCC, and 2BioMarin International Limited, Shanbally, Ringaskiddy, Co. Cork.

Investigation into the role of USP18 in the viability of oesophageal cancer cells.

Aidan O’Shea School of Clinical Therapies, College of Medicine and Health, UCC.

Exploring the barriers to and facilitators of self-management of people’s shoulder pain from the patient’s perspective: a focus group study.

13:30 – 14:50

Lunch with Poster Viewing and Networking session

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15:00 – 16:45

Session 3 CoMH Futures Co-Chaired by Prof. Finbarr Allen and Prof. Nicole Müller

15:00 – 15:25

Invited talk by Professor Gerry Lee School of Nursing & Midwifery, College of Medicine and Health, UCC.

EHRA-PATHS: Addressing multimorbidity in elderly atrial fibrillation patients through interdisciplinary, patient- centred, systematic care pathways.

15:25 – 16:05

Latest Advances 3 (8-minute research talks with questions) Dr Norma O’Leary School of Clinical Therapies, College of Medicine and Health, UCC.

Staff perceptions and experiences’ of using key word signing with children with Down syndrome and their peers, in the first year of mainstream primary education.

Ms Joanne Kelly 1

Cancer Research @UCC and 2CUH/UCC Cancer Centre, CUH.

Linking In with Advice and supports for Men impacted by Metastatic cancer: The LIAM Mc Trial.

Dr Jennifer Hollywood Department of Physiology, School of Medicine, College of Medicine & Health.

Using iPSCs and Kidney Organoids to Model Rare Kidney Disease to Find Better Treatments.

Dr Rosanne Raferty 1

Department of Anatomy and Neuroscience, and 2iEd Hub, College of Medicine and Health, University College Cork, Cork, Ireland.

Defining the ideal characteristics of stable human articular cartilage.

16:05 – 16:20

Elevator Pitches 3 (3-minute elevator pitch style talks, 1 question) Ciara Kidd School of Public Health, College of Medicine and Health, UCC.

The association between maternal threatened miscarriage and reported mental health in late adolescence Pádraig Cronin 1

School of Public Health, 2School of Medicine, College of Medicine and Health.

Development of an Impact evaluation framework for public and patient involvement (PPI) in hospice & palliative care research.

Aryth Stryker School of Nursing and Midwifery, College of Medicine and Health., UCC

Diabetes related stigma in women with type 2 diabetes of reproductive age.

16:20 – 16:45

Invited talk by Professor Denis O’Mahony Director of Research, HSE South West Region.

Experiences from the Coalface: Navigating the highs and lows of clinical trials for the benefit of patient care.

16:45 – 17:00

Closing remarks, prize announcement and close of the conference.

Prof. Gerard O’Keeffe, Vice Head of Research & Innovation, College of Medicine and Health, and Prof. Helen Whelton, Head of College of Medicine and Health and Chief Academic Officer to the HSE South West Region

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Invited Speakers’ Biographies Adaptive homeostasis in the lab, the clinic, and our institution!

Professor Ken D. O’Halloran, Professor and Chair, Department of Physiology, University College Cork.

Professor Ken O’Halloran is Professor of Physiology at University College Cork. He is an integrative physiologist with a long-standing interest in the control of breathing in health and disease. The focus of his research group at present is respiratory muscle physiology and neural control of respiratory behaviour in animal models of neuromuscular disease, ageing, and cancer cachexia. His research studies employ multidisciplinary approaches in pre-clinical models, and extend to include collaborative studies in clinical populations, and studies of cardiorespiratory and renal physiology in humans at high altitude. Ken is a Fellow of The Physiological Society, where he served as Trustee and Meetings Secretary, responsible for the scientific conference portfolio of The Society. He is a senior editor of Experimental Physiology and The Journal of Physiology.

Professor O’Halloran’s talk will take place in Session 1 from 09:10 – 09:35 in WGB_G05.

Public Health approaches to preventing suicide and self-harm: Progress and challenges.

Professor Ella Arensman, Head of School of Public Health, Professor of Public Mental Health, Chief Scientist, National Suicide Research Foundation, University College Cork.

Professor Ella Arensman is Head of the School of Public Health, Professor of Public Mental Health with the School of Public Health, College of Medicine and Health and Chief Scientist with the National Suicide Research Foundation, University College Cork. She is Vice President of the European Alliance Against Depression and past President of the International Association for Suicide Prevention. She is Visiting Professor with the Australian Institute for Suicide Research and Prevention, Griffith University, Brisbane, and an advisor for WHO. Over more than 35 years, she has initiated numerous national and international interdisciplinary research consortia on suicide and selfharm surveillance, intervention and prevention programmes for suicide, self-harm, depression, anxiety, and excess mortality among young people and adults with mental health conditions. Examples of ongoing research consortia and programmes include: Self-Harm Assessment and Management of Self-Harm in General Hospitals (SAMAGH), Adapting and Implementing EAAD´s Best Practice Model to Improve Depression Care and Prevent Suicidal Behaviour in Europe (EAAD-Best), Early Identification of Suicide and Self-Harm Risk and Comorbid Mental and Physical Disorders: An Interdisciplinary Training, Research and Intervention Programme (MHAINTAIN), Mental Health Promotion and Intervention in Occupational Settings” (MENTUPP), COVID-19: Estimating the burden of symptomatic disease in the community and the impact of public health measures on physical, mental and social wellbeing and Promoting Positive Mental and Physical Health at Work in a Changing Environment: A Multi-level Approach (PROSPERH).

Professor Arensman’s talk will take place in Session 2 from 12:10 – 12:35 in WGB_G05.

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EHRA-PATHS: Addressing multimorbidity in elderly atrial fibrillation patients through interdisciplinary, patient-centred, systematic care pathways.

Professor Gerry Lee, Professor of Nursing and Chair of Health Services Research, School of Nursing and Midwifery, University College Cork.

Professor Gerry Lee is a Professor of Nursing and Chair of Health Services Research at University College Cork in Ireland. She has worked in advanced practice for thirty years examining the role of nurse practitioner in relation to clinical outcomes. Her main research interests lie in cardiovascular disease, cardio-oncology and optimising health in longterm conditions using shared-decision making and digital technology. In 2018, she established a nurse-led rapid access clinic at St Thomas’s Hospital, London for patients with suspected atrial fibrillation and ran this clinic for 5 years. Professor Lee is an ex-officio member of the Council of Cardio-oncology at the European Society of Cardiology. She has published 150 peer reviewed publications and is a principal investigators on a Horizon 2020 European Union EHRA-PATHS study: 'Addressing multimorbidity in elderly atrial fibrillation patients through interdisciplinary, tailored, patientcentered care pathways.' (EHRA-PATHS).

Professor Lee’s talk will take place in Session 3 from 15:00 – 15:25 in WGB_G05.

Experiences from the Coalface: Navigating the highs and lows of clinical trials for the benefit of patient care.

Professor Denis O’Mahony, Director of Research, HSE South-West Region.

Professor Denis O’Mahony is a Professor in the Department of Medicine UCC and a Consultant Physician in Geriatric Medicine to Cork University Hospital and St. Finbarr's Hospital, Cork. Denis was appointed to the role of inaugural Director of Research in the HSE South-West Region, which is a new position in the HSE that will commence in 2025. His main research interests focus on Inappropriate prescribing and polypharmacy which are highly prevalent problems globally. These problems apply particularly in elderly patients with multiple comorbid medical conditions, requiring complex pharmacotherapy. Inappropriate prescribing and polypharmacy are associated with increased incidence of adverse drug events with consequently increased morbidity and mortality in this patient group. Denis and his colleagues have devised and validated new criteria for inappropriate prescribing in older people (STOPP/START criteria) aimed at applying them in routine clinical practice for the purpose of minimizing adverse drug reactions and events. His team have completed clinical trials showing that STOPP/START criteria as an intervention significantly improves medication appropriateness and reduces the rate of adverse drug reactions in acutely ill older patients in the hospital setting. Moreover, an on-going clinical trial funded through a Definitive Intervention and Feasibility Award from the Health Research Board is aiming to assess the effective of the intervention in the transition from hospital to primary care.

Professor O’Mahony’s talk will take place in Session 3 from 16:20 – 16:45 in WGB_G05.

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Oral Presentations Session 1: Latest Advances Revealing pathomechanims in neurodevelopmental and mental disorders by using human derived cellular models.

Sarah Kittel-Schneider1,2,3, Zora Schickardt3, Rhiannon V. McNeill3 1. Department of Psychiatry and Neurobehavioural Science, University College Cork 2. APC Microbiome, UCC 3. Dep. of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital of Würzburg Introduction: To investigate the role of genetic risk variants in complex Attention-Deficit-/Hyperactivity Disorder (ADHD) pathophysiology, advanced human in vitro models are required. Human induced pluripotent stem cells (hiPSC) are a valuable tool for modeling disorders of the central nervous system, as they have unlimited self-renewal and the capacity to differentiate into functional neurons.

Methods: We reprogrammed fibroblasts from human individuals suffering from ADHD and neurotypical controls into hiPSC. We differentiated them into neuronal cells and assessed the cellular phenotype with a focus on energy metabolism, glutamatergic signnaling and neuronal maturation.

Results: The data revealed disturbed cellular energy metabolism and mitochondrial dysfunction in both fibroblast and dopaminergic neuron cells, as well as gene expression changes. Unpublished data from ongoing projects is strengthening the first data with regards to lower ATP levels in ADHD PARK2 cortical neuronal cells and an abundance of reactive oxygen species under mitochondrial stress conditions. Furthermore, there are first hints at altered glutamatergic signalling, hypoexcitability and altered neuronal development in cortical neuronal cell cultures of ADHD patients compared to healthy controls.

Conclusions: The detected alterations in cellular functions in cells from affected individuals compared with those from neurotypical controls will be investigated in subsquent studies with regards to their potential to predict therapy response. We will rescue/normalise the observed alterations using stimulants as first line treatments and then investigate potential new treatments that are specifically targeting the detected imparied cellular functions in ADHD. Funding: Marie Skłodowska-Curie Horizon 2020 MinD project (SKS local coordinator); IZKF N-440 project (to SKS); BBRF project (to RBMcN).

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Acute stress, microbial metabolites and the microbiota-gut-brain axis: focus on microbial regulation of barrier function and hippocampal plasticity.

Cristina Rosell-Cardona1, Sarah-Jane Leigh1, Emily Knox1,2,3, Michael K Collins3, María R Aburto1, Kenneth O'Riordan1, Nancy Kelley-Loughnane4, Michael S Goodson4, John F Cryan1,3, Gerard Clarke1,5 1. APC Microbiome Ireland, University College Cork, Cork, Ireland 2. School of Pharmacy, University College Cork, Cork, Ireland 3. Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland 4. 711th Human Performance Wing, Air Force Research Laboratory, Wright-Patterson Air Force Base, Dayton, OH, USA 5. Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland Acute stress exposures are the building blocks of chronic stress. Unravelling the mechanisms underpinning the whole-body response to acute stress is critical to understand this neglected aspect of health and disease. A single acute stress exposure rapidly modulates gut-brain axis signalling including intestinal permeability and hippocampal plasticity. The gut microbiota is increasingly recognized as an important modulator of mood and cognition, and microbially-produced metabolites such as butyrate can be a key regulator of brain and gut function via the gut-brain axis. The aim of this work is to determine if acute stress regulates the microbial production of butyrate in the gut to modulate stress-induced alterations in barrier function and hippocampal plasticity. Mice underwent acute restraint stress, and butyrate production was analysed in caecal content at contemporaneous timepoints to LTP measured by electrophysiology. Colonic T84 epithelial and mouse brain endothelial (bEnd3) cells were used to evaluate barrier function by measuring transendothelial electrical resistance (TEER) and fluorescein isothiocyanate–dextran (FITC) flux with or without lipopolysaccharide (LPS) as a disrupting agent. Butyrate and acetate production were reduced in the caecal content at 45 min after the acute stress. Butyrate prevented LPS-induced disruption of gut and brain barrier function in a dose-dependent manner. We also expanded our evaluation of key electrophysiological indices of hippocampal plasticity, showing that LTP was modified following acute stress. In conclusion, acute restraint stress reduced the production of butyrate and altered hippocampal plasticity with implications for gut and brain barrier disruption. Future work will evaluate the role of butyrate in acute stress-induced alterations in hippocampal plasticity.

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Spectroscopy of oral potentially malignant disorders – towards a protocol for its use.

Edward Fahy1, Richeal Ní Ríordáin1 1. Cork University Dental School and Hospital Background: Diffuse reflectance spectroscopy (DRS) in healthcare refers to light passed through tissue and recorded as a spectrum. In cancer diagnostics, reports show high accuracy and immediate results with no removal of body tissue. It is not in clinical use in the mouth, and no protocol for its use has been published hitherto.

Oral cancer precursors in the mouth are a heterogenous group of at least eleven, known collectively as oral potentially malignant disorders (OPMD). The aims of this study were to (i) to formulate a clinical protocol for use of DRS in diagnosis of OPMD, (ii) to explore its clinical utility in the mouth and (iii) to review the protocol and assess its potential use in clinical practice.

Materials and Methods: An initial lab-based protocol was modified for clinical use based on a literature review. Recommendations were formulated based on the strength of the evidence. An initial study including ten patients was recruited to trial the protocol. A translational clinical research study (n=80) was carried out. All participants received DRS in the mouth. Interviews were carried out with users of the device and with clinicians.

Results: Implementation of a protocol for use of DRS in the mouth was successful. We acquired reliable data, and it was easy to use. However, the requirements of the technology were not practical for use in a clinical setting.

Conclusion: The protocol we formulated is usable as it currently stands and may be used as a basis for further research.

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The implementation and evaluation of a suicide prevention module for undergraduate health and social care students Michelle O'Driscoll1,2, Kerrie Gallagher1, Cliodhna O'Brien1, James O'Mahony3, Johnny Goodwin3, Maria O'Malley3, Laura J Sahm2, Aoife Fleming2, Paul Corcoran1,4, Jane McDonald1, Eve Griffin1,5.

1. National Suicide Research Foundation, UCC 2. School of Pharmacy, UCC 3. School of Nursing and Midwifery, UCC 4. School of Medicine, UCC 5. School of Public Health, UCC Background: The majority of those who die by suicide have contacted a healthcare provider within the year preceding their death. Yet, there is little to no suicide prevention training incorporated into health and social care courses, and healthcare professionals feel ill-equipped to support those at risk of suicide.

Aim: The aim of this study is to pilot a suicide prevention training module for undergraduate health and social care students, and evaluate its effectiveness and suitability.

Methods: An evidence-based suicide prevention module for health and social care students was designed by the National Suicide Research Foundation, funded by the HSE National Office for Suicide Prevention. A four-week iteration of the module is being piloted with 1st – 4th year undergraduate health and social care students at UCC and UCD in Semester 1 2024/2025. Session content includes suicide epidemiology, risk and protective factors, communication and safety planning. A certificate of completion will be provided, and participation is optional. Pre and post surveys will be completed, to evaluate course content and delivery.

Results: Findings related to suicide attitude, behaviour and competence, self-care, and interprofessional collaboration will be reported pre and post module, as well as course acceptability, feasibility and appropriateness upon completion.

Conclusions: The findings of this research will inform future iterations and SATLE-funded train-thetrainer development of this education, which will ultimately be made available to all health and social care courses nationally.

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Session 1: Elevator Pitches PREMI-NIRS: advanced NIRS signal analysis and machine learning for extremely preterm infants.

Ashoori M1, O’Toole JM2, McDonald FB1,2, Greisen G3, Dempsey EM2,4 1. Department of Physiology, School of Medicine, UCC 2. Infant Research Centre, UCC 3. SafeBoosC-III Consortium, Department of Neonatology, The Juliane Marie Centre, Rigshospitalet, Denmark.

4. Department of Paediatrics and Child Health, UCC The SafeBoosC-III trial was conducted to determine whether NIRS-derived rcSO2 monitoring in neonates improves short-term outcomes. We performed a follow-up analysis in a subset of this cohort to examine if features of NIRS can predict brain injury outcomes.

Ethical approval for the study was obtained from the Clinical Research Ethics Committee of the Cork Teaching Hospitals (ECM 4 (b) 12/09/2023). A total of 94 infants born at less than 28 weeks' gestational age had rcSO2 data recorded during the first 72 hours of life. The average duration of rcSO2 recordings was 60.29 hours. We applied machine learning methods to regional cerebral (rcSO2) and peripheral oxygen saturation (SpO2) signals to detect brain injury in extremely preterm infants. The rcSO2 and SpO2 signals were pre-processed. Numerous quantitative features were extracted from the bio-signals before and after exclusion of prolonged relative desaturations (PRDs) within the signals. PRDs were also evaluated as a stand-alone feature. A machine learning model was used to detect brain injury (Intraventricular haemorrhage-IVH grade III-IV) using a leave-one-out cross validation approach.

The area under the receiver operating characteristic curve (AUC) for the PRD rcSO2 was 0.78 (95% CI: 0.643 - 0.896). None of the other models generated were associated with brain injury.

There was a significant association between data-driven definition of PRDs in rcSO2 and brain injury.

We have recapitulated earlier findings published by our group. Automated analysis of PRDs of the cerebral NIRS signal in extremely preterm infants may aid, better prediction of IVH compared to a threshold-based approach

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Functional mapping of brain pathways involved in the gut microbial modulation of social behaviour.

Melanie M.J. Depret1,2, Nikki van Munsteren1,2, Mathieu Thabault1,2, Patrick Fitzgerald1,2, John F. Cryan1,2, Linda Katona1,2 1. APC Microbiome Ireland, University College Cork, 2. Department of Anatomy and Neuroscience, Cork, Ireland We live in a microbial world with trillions of microbes in and around us helping to digest food and regulating the immune system. Emerging data also suggest the critical influence of the gut microbiota on the brain impacting on behaviour and mental health. For example, the absence of gut microbes in experimentally derived germ-free mice results in impaired behaviours including reduced or complete lack of social interactions. Conversely, supplementation of deficient gut microbiota with probiotics and/or specific bacterial strains can restore social function. Despite a surge in such correlative demonstrations, the underlying neuronal mechanisms remain to be defined. We hypothesise, that one key central nervous system pathway for gut microbial influence on social behaviour originates from the vagus nerve through to the brainstem solitary nucleus (NTS) and its socially relevant afferent region the paraventricular hypothalamus (PVN). We aim to identify cell-type selective synaptic connections of this social gut microbial-brain pathway. We combined gut microbiota manipulation with behavioural testing, neuronal activity tagging, viral labelling and multichannel immunohistochemistry to explore the impact of antibiotics-mediated gut microbiota depletion on social behaviour and neuronal activity in adult mice of both sexes. First, we demonstrate that antibiotics altered the pattern of social interactions. Second, we observed differential neuronal cFos-activation in the NTS and PVN in antibiotics-treated vs control mice. Third, we uncovered molecularly diverse NTS neuron types projecting to the PVN. Our findings indicate alterations of social behaviour and related neuronal activity by gut microbial status, likely supported by diverse neuronal populations along the gut-vagusNTS-PVN pathway.

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SARS_COV-2-induced syncytia have enhanced procoagulant activity James V. Harte1,2,3, Vitaliy Mykytiv2, Maeve P. Crowley2,3, Caroline Coleman-Vaughan4, and Justin V. McCarthy1 1. Signal Transduction Laboratory, School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland 2. Department of Haematology, Cork University Hospital, Wilton, Cork, Ireland 3. EOLAS Research Group, Cork University Hospital, Wilton, Cork, Ireland 4. Department of Biological Sciences, Munster Technological University, Bishopstown, Cork, Ireland Introduction: Haemostatic markers are frequently altered from normal physiological ranges in patients with SARS-CoV-2-associated COVID-19. The coagulopathy involves the dysregulation and dysfunction of endogenous pathways; however, the pathophysiology remains poorly defined.

Recently, the formation of multinucleated giant cells, known as syncytia, have been recognised as a hallmark of severe and critical disease in patients with SARS-CoV-2-associated COVID-19. Cell-cell fusion and syncytiation is a physiological and pathological phenomenon, which interestingly has been linked to the activation of the coagulation cascade in vivo. Therefore, we investigated whether SARSCoV-2-induced syncytiation could promote cellular procoagulant activity in vitro.

Materials and Methods: Human-derived lung cells were transduced with SARS-CoV-2 virus-like particles (VLPs) to induce cell-cell fusion and syncytiation, and evaluated for changes in procoagulant activity by a modified procoagulant activity assay.

Results: The procoagulant activity of human lung cells was enhanced by SARS-CoV-2 VLPs, which reduced the lagphase to protofibril formation, increased the rate of fibrin polymerisation, and increased fibrin deposition. SARS-CoV-2-induced syncytiation markedly increased the externalisation of phosphatidylserine, leading to tissue factor-dependent procoagulant activity. Mechanistically, inhibition of calcium-dependent phosphatidylserine externalisation largely abolished the enhanced procoagulant activity, and inhibited the expansion, of SARS-CoV-2-induced syncytia. Pre-treatment with contemporary direct oral anticoagulants and heparins reversed the enhancement of procoagulant activity; however, in contrast to recent observations, treatment with anticoagulants had no effect on SARS-CoV-2-associated entry nor cell-cell fusion.

Conclusions: Collectively, transduction of human lung cells with SARS-CoV-2 enhanced cellular procoagulant activity by increasing tissue factor-dependent coagulation at the cellular surface in response to the externalisation of phosphatidylserine.

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Development of Polymeric Nanoparticles for Oral Delivery of RNA as a Treatment for Ileal Crohn’s Disease Miguel Ramôa1, Georgia Tsaridou1, Aida López Espinar1, Caitriona M. O’Driscoll1, Piotr S. Kowalski1,2 1. School of Pharmacy, UCC 2. APC Microbiome, UCC Crohn’s disease (CD) is a chronic inflammatory condition of the gastrointestinal tract with a global and accelerating incidence. Due to the side effects and loss of response to current treatments, an effective local therapy would bring considerable benefit. This project aims to develop an oral RNA-based treatment for ileal CD. For that, appropriate delivery vehicles are necessary to protect the RNA and withstand barriers such as intestinal fluid, digestive enzymes and mucus, ensuring effective delivery to the epithelium.

A chemically diverse library of amino-polyester (APE) polymers was used to produce APE-lipid nanoparticles (APE-LNPs) and evaluated for the delivery of messenger RNA (mRNA) and small interfering RNA (siRNA) to differentiated intestinal epithelial cell (Caco-2) monolayers. In addition, size, zeta potential, and RNA entrapment of APE-LNPs were assessed in the absence and presence of biorelevant intestinal medium (FaSSIF-V2).

APE-LNPs showed superior efficacy for siRNA (up to 80% protein knockdown) and mRNA delivery in differentiated monolayers compared to lipid nanoparticles containing leading ionisable lipids (SM-102 and ALC-0315) as used in the BioNTech/Pfizer and Moderna’s COVID-19 vaccines. A dependency was observed between polymer composition – in particular the side chain composition – and RNA delivery efficacy, and also with physicochemical stability in FaSSIF-V2. While select formulations preserved their size and RNA entrapment in this medium, RNA delivery was significantly impacted. Several formulation strategies are currently being tested to improve the efficacy of APE-LNPs in the presence of intestinal fluid and the remaining barriers in oral delivery.

Acknowledgements: Funded by the European Union (GA 101057491) and supported by the UK’s innovation agency, Innovate UK. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or the European Health and Digital Executive Agency (HADEA). Neither the European Union nor the granting authority can be held responsible for them.

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Session 2: Latest Advances Co-design, co-development and co-delivery of a new Introduction to Patient and Public Involvement (PPI) in Health and Social Care Research 5 ECTs Postgraduate Module.

Emmy Racine1, Niamh Dillon1, Edel Burton1, Denia Claudino1, Michelle Flood1, Patricia Kearney1, Lorna Kerin1, Larry Masterson1, Joanne Murphy1, Martin Quinn1, Jon Salsberg1, Stephanie Skeffington1, Carol Kelleher1.

1. School of Public Health, University College Cork.

PPI is defined as research being done ‘with’ or ‘by’ members of the public rather than ‘to’, ‘about’ or ‘for’ them. It is about actively involving members of the public in making decisions about what and how research is done.

In 2021, the National PPI Ignite Network was established. Funded by the Health Research Board, Irish Research Council and seven Irish higher education institutions (UCC, UL, NUIG, TCD, UCD, DCU and RCSI), the network aims to build capacity for high-quality PPI in health and social care research.

Overview: In 2023, PPI Ignite Network@UCC and PPI Ignite@UL led a collaborative development process for a new 5 ECTS Introduction to PPI in Health and Social Care Research postgraduate module.

Forty participants including HEI research and teaching staff, postgraduate students, individual PPI contributors and representatives from voluntary and charity organizations co-created the module format, structure, learning outcomes, content, and assessment.

On behalf of the PPI Ignite Network, the module was accredited in UCC and piloted in UCC and RCSI in April 2024. Eight workshops were co-delivered by researchers and teaching staff based in both universities with guest presentations from postgraduate students, PPI contributors and organisation representatives. Workshops 1-4 were delivered in-person and 5-8 online.

The pilot is currently being evaluated. Participants completed end-of-workshop and end-of-module questionnaires. Facilitators and guest speakers have provided accounts of what worked well/ not so well. Results will inform the national rollout of the module from October 2024 under a creative commons license. The module will be delivered in UCC annually with the next delivery in April 2025.

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Using innovative approaches to translational research in enhancing breastfeeding across healthcare settings Elaine Lehane1, Catherine Buckley2, Helen Mulcahy1, Elizabeth McCarthy1, Liz Cogan1, Rhona O’Connell1, Margaret Murphy1, Patricia Leahy-Warren1.

1. School of Nursing and Midwifery, University College Cork, Cork, Ireland 2. Northridge House Education and Research Centre, St Luke’s Home, Cork, Ireland Breastfeeding is a critical factor for early childhood health and development, yet rates in Ireland remain among the lowest globally. This study investigated the use of Participatory Action Research (PAR) and Work-Based Learning Groups (WBLGs) to enhance breastfeeding support practices among healthcare professionals across Irish healthcare settings, focusing on innovative approaches to translational research in health sciences.

Interdisciplinary healthcare professionals (n=94) and Public Patient Involvement (PPI) Mothers from maternity, primary, and community care settings participated in WBLGs over nine months. Facilitated by research and practice experts, these sessions encouraged reflective discussions and experiential learning to assess and improve breastfeeding support practices. Analysis of data identified five key themes—Empowerment, Ethos, Journey, Vision, and Personal Experience—emphasising the significance of knowledge-building and collaboration in supporting breastfeeding mothers and healthcare teams. Additional themes, such as Building Momentum and Being Present, highlighting the need for supportive environments that foster open dialogue and sustained engagement.

The findings offer valuable insights for advancing clinical practice and policy development in maternal and child health, providing a model that can be adapted and applied across diverse healthcare settings.

By promoting a culture of continuous learning and collaboration, this approach supports translational and clinical research that is central to the Academic Health Sciences and has potential for broader application beyond the Irish context.

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Perinatal stress and anxiety in Ireland: Sources, experiences, and support needs Ms Eibhlín Looney1, Dr Catherine Houghton2, Prof. Sarah Redsell3, Dr Karen Matvienko-Sikar1 1. School of Public Health, University College Cork, Cork, Ireland 2. School of Nursing and Midwifery, University of Galway, Galway, Ireland 3. School of Health Sciences, University of Nottingham, UK Aim: Perinatal stress and anxiety from conception to 2-years postpartum has important adverse outcomes for women and infants. This study examined women’s perceived sources and experiences of stress and anxiety during the first 1000 days to inform perinatal stress and anxiety reduction.

Women’s experiences and attitudes towards available supports, and their preferences for alterative supports and services were also investigated.

Methods: An online mixed-methods cross-sectional survey was conducted with pregnant women (n=214) and mothers of children ≤2 years (n=486) in Ireland. Participants completed closed-ended questions on stress, anxiety, perceived social-support, resilience, and sociodemographic, birth and child factors. Open-ended questions focused on participants’ experiences of stress and anxiety, and their support needs during pregnancy and/or postpartum. Quantitative descriptive and correlational analyses were conducted; qualitative data was analysed using thematic analysis.

Results: Higher stress and anxiety were associated with lower perceived social-support and resilience [all p<0.001]. Perinatal stress and/or anxiety were associated with previous mental health issues [p<0.001]. Experiencing pregnancy complications was associated with higher anxiety in mothers only [p=0.006]. Qualitative themes developed were: ‘perceived responsibilities’; ‘self-care’; ‘care for maternal health and wellbeing’; ‘social support’; and ‘access to support and information’.

Conclusions: Women’s experience of stress and anxiety is impacted by diverse factors related to the individual, interpersonal relationships, perinatal health and mental health outcomes, services and supports. The development of support-based individual-level interventions, coupled with improvements to service provision across the perinatal period is needed to support better care for women in Ireland, and improve future maternal and child outcomes.

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Wearable Enabled Symptom Assessment Algorithm (WESAA) - a novel remote monitoring solution for people with Parkinson's disease Colum Crowe1, Marco Sica1, Lorna Kenny2, Brendan O’Flynn1, David Scott Mueller3, Suzanne Timmons2, John Barton1, Salvatore Tedesco1 1. Tyndall National Institute 2. Centre of Gerontology and Rehabilitation, School of Medicine, UCC 3. Abbvie Inc. Parkinson's disease (PD) poses challenges in assessing and managing motor functions due to its varying symptoms, including sleep and cardiovascular issues. The Wearable Enabled Symptom Assessment Algorithm (WESAA) system addresses these challenges by enabling remote monitoring through wearable devices on the wrist and ankle. WESAA captures data on accelerations, angular velocities, photoplethysmography, and electrocardiogram signals, providing objective evaluations of PD aspects like motor symptoms, gait speed, sleep patterns, and blood pressure.

Our research aims to validate WESAA's effectiveness in real-life settings, focusing on its ability to detect motor symptoms amidst daily activities, potentially offering a valuable tool for physicians in adjusting treatments for people living with Parkinson's disease Initial findings from research reveal promising results, with machine learning models trained on wearable sensor data collected during scripted activities in laboratory settings achieving balanced accuracies of 83%, 75%, and 81% for tremor, bradykinesia, and dyskinesia detection, respectively.

However, when evaluated in unsupervised home environments, the performance of these models dropped to 63%, 63%, and 67% compared to self-assessment diaries, demonstrating the system’s current limitations.

In conclusion, the WESAA system holds significant promise as a tool for remote monitoring and management of Parkinson's disease symptoms. Through research and development efforts, we aim to enhance its capabilities and usability, ultimately improving the quality of care and quality of life for individuals affected by this condition.

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Session 2: Elevator Pitches A Prospective Observational Study on the Prevalence of Prescribing Cascades In Older Adults Admitted to Hospital Ruth Daunt1,2, Síobhán McGettigan1, Lorna Kelly2, Denis Curtin1, Denis O'Mahony1,2 1. School of Medicine, University College Cork 2. Department of Geriatric & Stroke Medicine, Cork University Hospital Introduction: Prescribing cascades (PCs) occur when unrecognized drug events are misdiagnosed as new clinical conditions resulting in prescription of inappropriate, unnecessary, or potentially hazardous additional drugs. Numerous examples have been described in the literature, however, there has been no published studies on the prevalence of PC in older acutely hospitalised adults.

Methods: We conducted a prospective observational study of adults 65years with multimorbidity and polypharmacy. Prescribing cascades were determined according to two predefined lists- Think Cascades [1] and an explicit list published by Doherty et al [2]. PCs were classified as ‘definite’, ‘probable’, ‘possible’, ‘uncertain’ or ‘indeterminate’ according to specific criteria.

Results: 385 patients were recruited (55% female, mean age 80.4years, SD 7.5). 39.4% (n=152) patients had a least one drug pair prescribed in the sequence of Drug A Drug B. A total of 325 drug pairs were identified. Of these, 33.5% (n=109) were probable or possible PCs, 66.5% (n=216) were uncertain PCs. Patients with a PC experienced higher mean level of polypharmacy than patients with no PCs (12 (IQR 9-14) vs 9 (IQR 7-11), p <0.001). The ratio of Drug A Drug B vs Drug B Drug A was 104/62= 1.68 using the ThinkCascade list and 210/83=2.53 using the Doherty list.

Conclusion: This study, the first to report the prospective prevalence of PCs, highlights that possible/ probable PCs are significantly prevalent among hospitalised multimorbid older adults.

References: 1. McCarthy LM, et al. Drugs & aging. 2022 Oct;39(10):829-40.

2. Doherty AS, et al. Pharmacology research & perspectives. 2022 Oct;10(5):e01008.

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Cardiovascular risk control in community-based Irish adults with dyslipidemia Rehab Elhiny1,2, Linda M. O'Keeffe3,4,5, Stephen Byrne1 Margaret Bermingham1 1. Pharmaceutical Care Research Group, School of Pharmacy, University College Cork 2. Clinical Pharmacy Department, Faculty of Pharmacy, Minia University, Minia, Egypt 3. School of Public Health, University College Cork 4. MRC Integrative Epidemiology Unit at the University of Bristol, University of Bristol 5. Population Health Sciences, Bristol Medical School, University of Bristol Background: In Ireland, cardiovascular diseases (CVD) are responsible for over 9,000 deaths annually, with ischemic heart disease (44%) and cerebrovascular disease (17%) being the primary contributors.

Elevated low-density lipoprotein cholesterol (LDL-C) is linked to cardiovascular deaths. Clinical guidelines set out LDL-C goals for patients at risk of CVD; however, the overall achievement of LDL-C goals remains low among individuals on lipid-lowering therapies (LLT). Aim: This study aims to assess the attainment of LDL-C goals in Ireland and to identify the effect of medication adherence on goal attainment.

Methods: As part of the Mitchelstown Cohort Rescreen in 2015, 1378 participants were recruited from a single primary care center. The Systematic Coronary Risk Evaluation (SCORE), including the updated versions SCORE2 and SCORE-OP, were used to predict cardiovascular risk for people with no previous diagnosis of cardiovascular disease. LDL-C goal achievement was assessed based on the recommended targets set by the 2011 ESC/EAS Guidelines. Medication adherence is assessed using self-reported from the patients. Medication and diagnosis data were extracted from electronic patient records.

Results: Among 1378 participants, 676 participants were on LLT. The majority, 565 (83.5%), were on statin monotherapy. Of the 604 participants who had their LDL-C measured, 262 (43%) achieved their recommended guideline goal for LDL-C. This includes 21 (19.8%) of the very high risk, 102 ( 43.7%) of the high risk, and 139 (52%) of the low-moderate risk patients. Of 50 participants who completed the self-reported medication adherence questionnaire, 23 participants were not considered adherent and 26 participants were adherent. Of 22 non-adherent participants wo had their LDL-C measured, 11 (50%) participants achieved goals.

Conclusion: Early findings demonstrate a potentially suboptimal prescribing of LLT, leading to a low level of guideline LDL-C goal attainment among people who required primary prevention of CVD, which is concerning.

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Investigation into the role of USP18 in the viability of oesophageal cancer cells Maria M. Carey1, Tracey R. O’Donovan1, Chloe Coveney2, Sharon L. McKenna1.

1. CancerResearch @UCC, College of Medicine and Health, University College Cork, Ireland 2. BioMarin International Limited, Shanbally, Ringaskiddy, Co. Cork Oesophageal cancer is one of the most difficult cancers to treat, often exhibiting resistance to current treatments (chemo-or radio-therapy). The five-year survival rate for patients is less than 20% across Europe. Thus, new treatment approaches are urgently required.

The Autophagy group at CancerResearch @UCC has found differential expression of the ISGylation network in cells that respond differently to drug treatment. ISGylation is a mechanism similar to ubiquitination, where ISG15 is conjugated to targets via the sequential cooperation of E1, E2 and E3 enzymes. Ubiquitin Specific Peptidase 18 (USP18), an ISG15-specific enzyme, can remove ISG15, reversing this reaction.

We are investigating the role of USP18 in oesophageal cancer cells. We have shown that siRNA mediated knockdown (KD) of USP18, in the presence of IFN-α, increases the sensitivity of KYSE450 and KYSE140 cell lines to the chemotherapeutic agents 5-fluorouracil (5-FU) or Oxaliplatin (OX).

Importantly, this chemo-sensitisation is associated with the induction of apoptosis in these “apoptosis incompetent” cell lines. In addition, USP18KD in the presence of IFN-α and 5-FU or OX, upregulated autophagy as demonstrated by elevation of autophagosomes (Cyto-ID assay) and expression of the autophagy marker LC3II (western blot). We are now utilising mass spectrometry to identify targets of USP18 that might mediate viability.

These data identify USP18 as a regulator of two pathways that can influence drug sensitivity in oesophageal cancer cells. Ultimately, we aim to examine the mechanisms underpinning these effects and determine whether USP18 or a downstream mediator are potential targets for therapeutic benefit in oesophageal cancer.

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Exploring the barriers to and facilitators of self-management of people’s shoulder pain from the patient’s perspective: a focus group study Aidan O'Shea1, Jonathan Drennan2, Chris Littlewood3, Helen Slater4, Julius Sim5, Joseph G. McVeigh1 1. Discipline of Physiotherapy, College of Medicine and Health, University College Cork.

2. School of Nursing, Midwifery and Health Systems, College of Health and Agricultural Sciences, University College Dublin.

3. Faculty of Health, Social Care & Medicine, Edge Hill University, Ormskirk, United Kingdom.

4. Curtin School of Allied Health, enAble Institute, Curtin University, Perth, Australia.

5. School of Allied Health Professions, Faculty of Medicine and Health Sciences, Keele University, Keele, United Kingdom.

Background: Research suggests that shoulder pain is resistant to treatment and possibly recurrent in nature. Therefore, self-management that equips patients with the necessary tools to manage their condition may be the most appropriate intervention and may result in improved long-term outcomes.

However, the evidence to date does not indicate that self-management is more effective than other interventions for shoulder pain. A reason for limited success with self-management may be poor patient engagement. Developing a greater understanding of the barriers and facilitators related to selfmanagement of shoulder pain is therefore required.

Methods: This focus group study was designed using the Theoretical Domains Framework. Five online focus groups were conducted, each containing 3–4 participants (total n = 17) with shoulder pain. Data were analysed deductively, using reflexive thematic analysis.

Results: Three themes were identified that influenced self-management: (1) support for selfmanagement (subthemes related to knowledge, social influences, role of the clinician, and personalised care); (2) personal factors (subthemes related to patient beliefs, therapeutic response, patient intentions, pain, and emotion); and (3) external factors (subthemes related to influence of the clinician and environmental context and resources).

Conclusion: This study identified barriers and facilitators relating to self-management of people’s shoulder pain that might explain, in part, why existing self-management programmes are not always effective. Critically, the results of this study could stimulate informed discussion about the future delivery of self-management programmes for people with shoulder pain and the requirement to upskill clinicians to effectively support patients and implement behaviour change strategies.

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Session 3: Latest Advances Staff perceptions’ and experiences’ of using key word signing with children with Down syndrome and their peers, in the first year of mainstream primary education Norma O’Leary1, Caoimhe Lyons1, Pauline Frizelle1 1. Department of Speech and Hearing Sciences, University College Cork.

Background: Key Word Signing (KWS) is one system which can be used to support the communication needs of children with Down Syndrome (DS) who attend mainstream school. The success of using KWS in schools is mediated by staff experiences and perceptions of KWS. Aim: Given the current dearth of research in this area, the current study aimed to explore the perceptions and experiences of teachers and Special Needs Assistants (SNAs) with reported varying levels of experience, using KWS with children with DS and their peers, in the first year of mainstream primary school. Secondly, we aimed to explore how those perceptions and experiences evolved throughout the year.

Method: Five mainstream schools were recruited where children with DS attended. An SLT researcher taught twenty-five key word signs to the relevant class in each school at four time points across the year. Five teachers and 8 SNAs from participating schools engaged in a series of interviews about to explore in-depth their perceptions / experiences of using Lámh over the course of the year. Data were analysed using inductive qualitative content analysis.

Results: Four categories were generated from the data: Challenges, Facilitators, Benefits, and Incorporation into Whole School Environment. Findings suggest that the supported introduction of KWS in school, in the case of this study by an SLT researcher, can assist inclusive educational practices; facilitate children’s comprehension and expression; reduce frustration in children with DS; and facilitate interaction with peers. Results also indicate an increasingly positive attitude, among teachers and SNAs, towards KWS as the year progressed. Teachers reported the absence of a pedagogical framework as an obstacle to the integration of KWS into the curriculum, while SNAs highlighted inconsistent access to funded entry-level training.

Conclusion: Overall, using KWS was a positive experience that supported communication in children with DS in mainstream school. However, future training should embed knowledge on key facilitators and consider how challenges can be addressed, to maximise the potential of all children with communication needs attending mainstream primary school.

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Linking In with Advice and supports for Men impacted by Metastatic cancer: The LIAM Mc Trial Jack P. Gleeson1,2, Anita Cahill1,2,3, Katie E. Johnston1,2,4, Stephanie Corkery1,2,5, Katarina Medved1, Anne-Marie Cusack1, Joanne Kelly1,2, Denise Stenson Russell1,2, Laia Raigal-Aran1, Josephine Hegarty6, Roisin M. Connolly1,2, Mohamad M. Saab6, Richard M. Bambury1,2 and Brendan Noonan6 1. Cancer Research @UCC, College of Medicine & Health, University College Cork, Ireland 2. CUH/UCC Cancer Centre, Cork University Hospital, Cork 3. Department of Urology, Cork University Hospital, Ireland 4. Clinical Nutrition and Oncology Research Group, School of Food and Nutritional Sciences, University College Cork, Ireland 5. Department of Physiotherapy, Cork University Hospital, Ireland 6. Catherine McAuley School of Nursing and Midwifery, University College Cork, Ireland Background: Multidisciplinary supportive care interventions are key to preventing and managing adverse effects from cancer treatment, reducing symptom and psychological burdens and enhancing quality of life (QoL). The optimal composition of interventions for men with genitourinary (GU) cancers is poorly understood. The LIAM Mc Trial is an enhanced supportive care programme, designed with patient input. The study aims to assess the feasibility of introducing a supportive care programme alongside routine oncology follow up for men with metastatic cancer, and to determine the benefits of this approach.

Methods: Using an embedded mixed-method process evaluation, this prospective trial involves a holistic 12-week survivorship programme comprising twice-weekly sessions with input from a physiotherapist, dietitian, and nurse specialist, and education from community supports, psychooncology and medical social work. Outcomes are measured at baseline, 12 weeks and 6 months. These include QoL (EORTC-QLQ-C30 & EQ-5D-5L); muscle strength; body composition (bioelectrical impedance analysis & ultrasound); diet quality; cancer-related symptom control; cancer-related fatigue scores (EORTC QLQ-FA12); feasibility outcomes and qualitative interviews. Men with a locally advanced or metastatic GU cancer who have recently completed a course of treatment or are stable on active anti-cancer treatment are eligible for the programme. Acceptability, satisfaction with the programme and barriers to participation are key secondary endpoints. The target sample size is 72.

The study began recruiting in May 2023, and at time of submission, 24 participants have enrolled in the trial. ClinicalTrials.gov: NCT05946993

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Using iPSCs and Kidney Organoids to Model Rare Kidney Disease to Find Better Treatments Jennifer A. Hollywood1 1. Department of Physiology, University College Cork, Ireland The generation of induced pluripotent stem (iPS) cells from patients with hereditary diseases and the differentiation of these cells into mini organs (organoids) provides a new way to study and find treatments for illnesses in vitro. The lysosomal storage disease nephropathic cystinosis results from mutations in CTNS, encoding a cystine transporter, and initially causes kidney proximal tubule dysfunction followed by kidney failure.

Cystinosis is currently treated with the cystine-depleting drug cysteamine, however this only slows the progression of the disease. Thus, there is a pressing need for better treatments. Here, we have characterised cystinotic iPS cell lines (CTNS-iPSCs) made from an individual with nephropathic cystinosis and in isogenically matched cells via CRISPR/Cas9 gene editing. CTNS-iPSCs and kidney organoids, differentiated from these cells, display elevated cystine levels, enlarged lysosomes and a block in basal autophagy flux. We found that cysteamine treatment of CTNS-iPSCs and kidney organoids lowers cystine levels, reduces the number of large lysosomes but does not correct the basal autophagy flux defect. Treating the cells with an inhibitor of the mTOR pathway, reduces the number of large lysosomes and activates autophagy but did not rescue the cystine loading. However, dual treatment of CTNS-iPSCs and kidney organoids with cysteamine and mTOR inhibitor corrected all the observed phenotypes suggesting that a combination therapy may have clinical value as an improved treatment of cystinosis. Together, our results indicate that the iPSC/organoid platform can be used to model cystinosis and suggest that mTOR-inhibiting drugs have therapeutic value in the treatment of this disease.

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Defining the ideal characteristics of stable human articular cartilage.

Rosanne M. Raftery1,2,3, Steven K. Pregizer2,3, Divya Venkatasubramanian2, April M. Craft2,3 1. iEd Hub and Department of Anatomy and Neuroscience, School of Medicine, University College Cork, Cork, Ireland 2. Department of Orthopedic Research, Boston Children’s Hospital, Boston, MA USA 3. Department of Orthopedic Surgery, Harvard Medical School, Boston, MA USA Articular cartilage is a stable, long-lasting tissue found on the articulating surface of our joints, however, when damaged, the resident articular chondrocytes reactivate developmental processes, generating inadequate repair tissue akin to growth plate cartilage. Understanding the processes involved in development and maintenance of articular cartilage may reveal molecular candidates for disease treatment and prevention. We previously established protocols that recapitulate key events during cartilage development, inducing human pluripotent stem cells (hPSCs) to differentiate into articular or growth plate chondrocytes. In this study, these distinct cell culture models were used to determine if hPSC-derived articular chondrocytes can function as permanent cartilage, an important characteristic for clinical translation. Unlike hPSC-derived growth plate chondrocytes or mesenchymal stem cells (MSCs), hPSC-derived articular chondrocytes were phenotypically stable throughout the 6month-long in vitro study. BMP4 treatment can induce a lineage switch from articular to growth plate chondrocytes. By challenging articular chondrocytes with BMP4 at different time-points, we discovered that articular chondrocytes become stable approximately 10-weeks into the differentiation protocol. Using scRNAseq, we captured transcriptomic changes during differentiation in real-time. We also studied the cells response to BMP4 challenge early in differentiation, when cells can switch lineage to growth plate cartilage, and compared it to the response by 10-week-old lineage restricted cells, revealing a key role of the extracellular matrix in controlling cell signalling and behaviour. The knowledge gained in this study helped define the ideal cell characteristics for safe and efficient cell therapy, while the data generated reveals important information about cartilage development.

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Session 3: Elevator Pitches The association between maternal threatened miscarriage and reported mental health in late adolescence Ciara Kidd1, David O’ Driscoll1,2, Laura J. O’Byrne3,4, Gerard W. O’Keeffe5, Ali S. Khashan1,3, Gillian M. Maher1,3 1. School of Public Health, UCC. 2. Specialist Neurodevelopmental ADHD Pathway (SNAP), Cork Kerry Mental Health Service.

3. INFANT Research Centre, UCC. 4. Department of Obstetrics and Gynaecology, Cork University Maternity Hospital, UCC. 5. Department of Anatomy and Neuroscience, UCC. Background: Childhood mental health is a known determinant of health across the lifespan underscoring the importance of identifying determining factors. Threatened miscarriage is a common pregnancy complication, yet its influence on child mental health outcomes is unclear. Here we examined the association between threatened miscarriage and the risk of depression/anxiety by late adolescence using the representative prospective longitudinal UK Millennium Cohort.

Methods: Data on threatened miscarriage (defined as bleeding in early pregnancy) and potential confounders were collected at 9-months postpartum. Data on depression/anxiety were collected as one variable when the children were aged 17-years using self-reported diagnosis by a doctor.

Multivariable logistic regression analysis examined the association between threatened miscarriage and depression/anxiety in the child, adjusting for several maternal and sociodemographic factors.

Mediation analysis was used to examine the mediating role of small for gestational age (SGA) and preterm birth (PTB).

Results: N=9,521 mother-child dyads were included in the analyses, and n=574 (6%) of these women experienced a threatened miscarriage. Adjusted analysis showed that threatened miscarriage was associated with a 34% increase in the odds of depression/anxiety (adjusted odds ratio, aOR: 1.34, 95% CI 1.03,1.73) in the children by age 17 years. This association was not mediated through SGA (natural indirect effect (NIE): 0.99, 95% CI 0.98, 1.01) or PTB (NIE: 1.05, 95% CI 0.99, 1.12).

Conclusion: Threatened miscarriage was associated with an increased risk of depression/anxiety in adolescent offspring, albeit residual or unmeasured confounding cannot be ruled out. Future research should examine the potential biological mechanisms mediating this association.

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Development of an Impact Evaluation Framework for Public and Patient Involvement (PPI) in Hospice & Palliative Care Research Pádraig Cronin1, Jane Clare2, Mary Rabbitte2, Emmy Racine1, Patricia Kearney1, Carol Kelleher1 1. PPI Ignite Network@ UCC, School of Public Health, University College Cork 2. All Ireland Institute for Hospice and Palliative Care Background: Public and Patient Involvement (PPI) describes research that is conducted ‘with’ or ‘by’ the public, rather than ‘to’, ‘about’ or ‘for’ them. One area of research lacking PPI is in the measurement of impact outcomes in Hospice and Palliative Care. This project aimed to develop a framework for evaluating PPI outcomes in this field through a collaboration between the PPI Ignite Network@ UCC and the All-Ireland Institute of Hospice and Palliative Care (AIIHPC).

Methods: This study utilised a two-step approach. Firstly, a review of existing PPI and research impact evaluation frameworks to develop a new evaluation tool. Secondly, two focus groups were conducted with six contributors from the Voices4Care and PCRN/ECRF networks, to identify key themes for evaluating PPI impact in hospice and palliative care. The results of both approaches were used to inform the development of a new framework to measure PPI outcome.

Results: The Voices4Care focus group identified key long-term impacts to track, such as Clinical Adaption of Research, Empowerment of PPI Contributors, Increased Awareness of Palliative Care, and Influencing Healthcare Professional Training. The PCRN/ECRF group suggested a shift from traditional academic metrics to a whole-lifecycle project analysis, with the inclusion of guidance notes to assist researchers in completing such a framework. The use of an Impact Narrative was identified as being particularly beneficial for the capture of long-term qualitative impacts.

Conclusions: This PPI Impact Evaluation Framework for Hospice and Palliative Care Research provides researchers with a tool to effectively measure and implement contributor desired impacts into the project outcomes.

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Diabetes related stigma in women with type 2 diabetes of reproductive age.

Aryth Stryker1, Dr Aileen Burton1, Dr Rita Forde1 1. School of Nursing and Midwifery, UCC Background: Pregnancies complicated by type 2 diabetes (T2DM) are increasing. These pregnancies pose significant risks such as higher rates of congenital anomalies, stillbirths, and neonatal mortality compared to pregnancies among women with type 1 diabetes. T2DM in younger women is more medically complex than when diagnosed at older ages. Women with T2DM experience high levels of stigma which intensify during pregnancy through heightened scrutiny of their lifestyle choices and increased emotional stress related to the potential risks to their baby, further complicating their diabetes self-management.

Methods: A secondary analysis of a qualitative dataset of interviews exploring experiences of prepregnancy care with women living with T2DM (n=30) and healthcare professionals (n=22) was conducted to elicit stigma experiences relative to type 2 diabetes. Identified data was analysed thematically to explore the drivers and triggers of stigma in this group.

Findings: Stigma was expressed in interactions with healthcare professionals, family members and friends through societal narratives and self-perceptions which negatively affected diabetes care relationships with healthcare providers and general wellbeing. For some women stigma was internalised and expressed as negative self-directed feelings (shame and guilt). Healthcare professionals often perpetuated these stigmatising ideations through the conflation of obesity and T2DM aetiology as being the personal lifestyle behaviours of the women.

Conclusion: Women with T2DM experience stigma from multiple sources, one being healthcare interactions which can negatively impact their healthcare behaviours and engagement. Strategies are needed to challenge existing narratives and to equip healthcare professionals with the necessary skills to have constructive conversations.

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Poster Presentations Factors Influencing Medication Adherence Among People With Anxiety Or Depression: A Cross-Sectional Study Using Data From The Mitchelstown Cohort Rescreen Study 2015 Louise Hearne1, Edel Burton1,2,3, Margaret Bermingham1 1. Pharmaceutical Care Research Group, School of Pharmacy, University College Cork.

2. School of Public Health, University College Cork.

3. Pharmacy Department, Bons Secours Hospital, Cork.

Aim: Medication adherence is essential for achieving optimal treatment outcomes in managing depressive and anxiety disorders. The aim of this study is to assess levels of medication adherence in these patient cohorts and investigate the factors which may influence medication adherence.

Methods: This study is a secondary analysis with a cross-sectional design of data from the Mitchelstown Cohort Re-Screen (MCR) Study 2015. Participants were included if they had a diagnosis of anxiety or depression. The Morisky Medication Adherence Scale 8 was used to measure medication adherence. A score of 8 means that a patient is fully adherent to their medication regime while a score less than 6 indicates non-adherence. Descriptive statistics, univariable, binary logistic regression and multivariable multinomial logistic regression models were conducted.

Results: Out of 1378 participants in the MCR, 145 were living with depression and 159 with anxiety.

The mean age of those with depression or anxiety was 65.28 (SD 5.4) years, and 49.35% of participants were female. Of those with depression 17.24% (n=25) of were non-adherent (MMAS<6) compared with 9.94% (n=136) of those in the MCR not suffering from depression or anxiety . Having depression was associated with decreased medication adherence (OR=1.755, 95%CI=1.182-2.607), whilst no significant association was found between anxiety and adherence (OR=1.296, 95%CI=0.614-2.372).

Socio-economic factors showed no significance in multivariable models.

Discussion: Lower levels of medication adherence in those living with depression were reported which aligns with other studies conducted on this matter. Thus, specific interventions to optimise adherence in this cohort should be considered.

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Can Artificial Intelligence (AI) be responsibly harnessed to increase public health literacy and trust in our national health information website? A feasibility assessment for implementing policy into practice Julie M Arnott1, Kevin Horan2, Ben Cloney2 1. School of Public Health, UCC 2. HSE Digital, Communications Division, HSE Background: The World Health Organisation called the COVID-19 'infodemic' unprecedented. Artificial Intelligence (AI) has been proposed as an upstream infodemic intervention to build public trust in health information.

Methods: To assess the feasibility of implementing national AI policy into practice for the national Health Service Executive (HSE) website, an evidence-based framework for responsible AI development in healthcare was utilised. This framework is underpinned by virtue ethics assessed under five themes: Sustainable, Human-centric, Inclusive, Fair, Transparent (SHIFT).

Findings: Sustainable? A strategic service-academic partnership has been formed to develop a responsible solution that serves local needs.

Human-centric? Baseline data from the HSE’s user experience team and engagement with service users will inform this AI development.

Inclusive? The website is also only available in two languages, English or Irish. AI functionality features will be explored, such as language translation and talk-to-text. Testing will specifically target groups with limited digital health literacy.

Fair? To avoid development bias, the existing HSE website will be used which has existing clinical governance in place. Technology guardrails will provide quality assurance of clinical health information.

Transparent? This AI solution will be developed and governed by the HSE and will not require personal data for development.

Conclusion: Using the SHIFT framework, AI will be developed in a responsible, sustainable, and ethical manner. AI has the potential to promote health-information-seeking on a trustworthy website to increase the public’s health literacy, improve self-efficacy, reduce health anxiety, and prevent unnecessary healthcare utilisation.

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Tracking Parkinson’s Disease symptoms and medications across the menstrual cycle.

Sarah Moore1,2,3, Lucy Collins-Stack2,3, Aonghus Lavelle2, Aideen M. Sullivan1,3 1. Department of Pharmacology and Therapeutics, School of Medicine, University College Cork, Ireland 2. Department of Anatomy and Neuroscience, School of Medicine, University College Cork, Ireland 3. Parkinson’s Disease Research Cluster, University College Cork, Ireland Parkinson's Disease (PD) affects ~1-2% of the population aged over 60, yet gender-specific differences in symptoms and treatment responses are underexplored. This study investigates the impact of hormonal fluctuations across the menstrual cycle on symptoms and medication efficacy in women with PD, using both ‘My Moves Matter’ app and REDCap-based surveys for data collection. Participants were recruited through ‘My Moves Matter’ app and Parkinson’s support groups. The ‘My Moves Matter’ app enables real-time collection of patient-entered data, enhancing patient engagement.

Participants log symptoms, medication intake and menstruation status daily, providing a detailed, longitudinal dataset for the analysis of correlations and patterns. Participants begin by completing an initial survey, followed by a 4-month period of tracking using the ‘My Moves Matter app’. At the end of this timeframe, participants complete a follow-up survey. The data collected across these three phases allow for analysis of correlations between app-reported data and changes observed from the initial to the follow-up survey.

Preliminary findings indicated correlations between worsening of both speech and handwriting, and stage of menstruation cycle. Analysis is ongoing, including data on symptoms and medication use, across menstrual cycle stages in the study cohort.

Data from this study will facilitate the development of treatment and disease-management strategies for women with PD. Real-time monitoring could facilitate timely adjustments to treatment plans, improving symptoms management. This research underscores the importance of personalised management plans for women with PD, aiming to enhance quality of life by addressing the unique challenges posed by hormonal fluctuations.

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Stakeholder perceptions of and attitudes towards problematic polypharmacy and prescribing cascades: a qualitative study.

Aisling A. Jennings1, Ann Sinéad Doherty1; Barbara Clyne2; Fiona Boland3,4; Frank Moriarty5; Tom Fahey3; Larry Hally6; Seán P Kennelly7,8; Emma Wallace1 1. Department of General Practice, University College Cork, Cork, Ireland.

2. RCSI University of Medicine and Health Sciences, Dublin, Ireland.

3. HRB Centre for Primary Care Research, Department of General Practice, RCSI University of Medicine and Health Sciences, Dublin, Ireland.

4. Data Science Centre, School of Population Health, RCSI University of Medicine and Health Sciences, Dublin, Ireland.

5. School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin, Ireland.

6. PPI Representative and Vice Chair of the Clare branch of the Older People’s Council, Ireland.

7. Department of Medical Gerontology, School of Medicine, Trinity College Dublin, Dublin, Ireland.

8. Department of Age-related Healthcare, Tallaght University Hospital, Dublin, Ireland.

Introduction: Problematic polypharmacy is the prescribing of five or more medications potentially inappropriately. Unintentional prescribing cascades represent an under-researched aspect of problematic polypharmacy and occur when an adverse drug reaction (ADR) is misinterpreted as a new symptom which results in the initiation of a new medication. The aim of this study was to elicit key stakeholders’ perceptions of and attitudes towards problematic polypharmacy, with a focus on prescribing cascades.

Methods: Qualitative one-to-one semi-structured interviews were conducted with predefined key stakeholder groups. Inductive thematic analysis was employed.

Results: Thirty-one stakeholders were interviewed: six patients, two carers, seven GPs, eight pharmacists, four hospital doctors, two professional organisation representatives, and two policymakers. Three main themes were identified: i) ADRs and prescribing cascades – a necessary evil.

Healthcare professionals (HCPs) expressed concern that experiencing an ADR would negatively impact patients’ confidence in their doctor. However, patients viewed ADRs pragmatically as an unpredictable risk. ii) Balancing the risk/benefit tipping point. The complexity of prescribing decisions in the context of polypharmacy made balancing this tipping point challenging. Consequently, HCPs avoided medication changes. iii) The minefield of medication reconciliation. Stakeholders, including patients and carers, viewed medication reconciliation as a perilous activity due to systemic communication deficits.

Conclusion: Stakeholders believed that at a certain depth of polypharmacy, the risk that a new symptom is being caused by an existing medication becomes incalculable. Therefore, in the absence of harm, medication changes were avoided. However, medication reconciliation post hospital discharge compelled prescribing decisions and was seen as a high-risk activity by stakeholders.

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Evaluation of a Complex Survivorship Intervention incorporating Electronic Patient -Reported Outcomes in Early-Stage Breast and Gynaecologic Cancer: Results from the Linking You to Support and Advice (LYSA) Randomised Control Trial (RCT) Kate O’Connell1,2*, Laia Raigal1*, Katie E.Johnston2,3, Samantha Cushen3, Andrea Davis2, Fiona Byrne2, Naoimh Flynn1,2, Seamus O’Reilly1,2, Sinead Noonan1,2, Dearbhaile Collins1,2, Vicki Cleary2,4, Katarina Medved1, Noreen Kearns1,8, Aileen Murphy5, Brendan Palmer6,7 Darren Dahly6,7, Josephine Hegarty8^, Roisin M. Connolly1,2^ (*^ These authors have contributed equally) 1. Cancer Research @UCC, College of Medicine & Health, University College Cork (UCC), Cork, Ireland.

2. CUH/UCC Cancer Centre, Cork University Hospital, Cork, Ireland.

3. Clinical Nutrition & Oncology Research Group, School of Food & Nutritional Sciences, UCC, Ireland.

4. Department of Gynaecologic Oncology, Cork University Maternity Hospital, Cork, Ireland.

5. Cork University Business School, UCC, Ireland.

6. HRB Clinical Research Facility, UCC, Cork, Ireland.

7. School of Public Health, UCC, Cork, Ireland.

8. Catherine McAuley School of Nursing and Midwifery, UCC, Cork, Ireland.

LYSA a multisite Randomised Controlled Trial (RCT) with parallel arms (experimental and active comparator), co-designed with public and patient involvement, evaluated the feasibility of introducing a women’s survivorship clinic into routine care at 2 Irish Cancer Centres. Eligible participants had gynaecologic or early-stage hormone sensitive breast cancer, within 12 months of completing primary therapy (NCT05035173). Experimental arm participants completed Electronic Patient-Reported Outcome (ePRO) assessments at baseline and bimonthly to 12 months. An online trigger alert system facilitated symptom management via a nurse-led clinic and dietetic consultation. Active comparator arm participants attended the nurse-led clinic at baseline and end of study, with routine care in the interim. Target accrued of 200 women, March 2021-August 2022.

173 participants completed the study (n=90 experimental, n=83 comparator). Following symptom triggers, there were 322 study nurse visits across 86 participants, and 243 dietitian visits across 73 participants. Engagement with healthcare and other supportive resources was approximately twice more in the experimental group compared to the control group. The experimental arm participants had better EORTC total scores at study end relative to comparator (difference in means -3.87 95%CI 6.58 to -1.16, p=0.005). There were also significant differences (p < 0.05) observed between the arms for symptoms, reflecting less fatigue, and lower anxiety and depression levels at study end.

The LYSA trial met its primary endpoint of feasibility, with high rates of ePRO completion via an online electronic data capture platform. Additional secondary endpoint analysis is ongoing, including an economic analysis and will guide future study design.

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The Practice Changing Linking You to Support and Advice [LYSA] Randomised Control Trial: A Patient-Guided Multidisciplinary Survivorship Trial Kate O’Connell1,2*, Katie E Johnston1,2,3*, Naoimh Flynn1,2, Laia Raigal-Aran1, Samantha J Cushen1,3, Katarina Medved1,4, Darren Dahly4, Brendan Palmer4, Josephine Hegarty5^ and Roisin M Connolly1,2^ (*^These authors have contributed equally) 1. Cancer Research @UCC, University College Cork, Cork, 2. UCC/CUH Cancer Centre, Cork University Hospital 3. Clinical Nutrition and Oncology Research Group, School of Food and Nutritional Sciences, University College Cork, Cork, 4. Clinical Research Facility Cork, School of Public Health, University College Cork, Cork, 5. Catherine McAuley School of Nursing, University College Cork, Cork, Ireland Background: Research highlights the needs of cancer survivors are currently not being met. Digital platforms are a promising, innovative way to deliver holistic, patient-centered care. The LYSA Trial focused on nurse- and dietitian-led clinics using digital platforms that centered around patient collaboration and participation.

Methods: The LYSA Trial (n=200) was a multisite, parallel-arm, RCT. Participants attended the clinic at baseline and 12 months. All patients received an individualised treatment summary and care plan and signposting to post-treatment care and services.

The experimental arm received education and symptom management pathways tailored to electronic patient reported outcome (ePROs) assessments bi-monthly. A trigger system developed highlighted bothersome symptoms through ePRO scores. The support system ranged from supported selfmanagement to onsite and community specialist support. Patient responses guided collaborative treatment strategies specific to individual needs.

The Public and Patient Involvement (PPI) Panel was made up of patient advocates and stakeholders.

This group were pivotal in the design, development and implementation of the clinic. This PPI Panel is presently at the forefront of analysis and dissemination.

Implications: As a direct result of the LYSA Trial, a Women’s Health Initiative Clinical Nurse Specialist has been appointed to CUH. Resources (treatment summaries, care plans and symptom pathways) and expertise initiated and developed during the trial are guiding and supporting clinical practice.

Educational gaps have been identified. Dietetic resources for menopausal cancer survivors are being developed with the Irish Cancer Society. Educational events for health care professionals have been implemented.

Infrastructural changes to research practices, including patient information leaflets and PPI Panels, have been highlighted as areas for expansion and improvement to allow for diversity, equity and inclusion for future research.

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Irish College of General Practitioners’ (ICGP) trainee experiences following transition from hospital to general practice: a qualitative study.

Fodhla Ni Dhalaigh1, Alice O'Neill2, Tony Foley1, Orna Daly2, Michelle Martin2, Helen McHugh2, Aisling Jennings1,2 1. School of Medicine, UCC 2. Irish College of General Practitioners, Cork GP Training Scheme Background: Specialist training in General Practice in Ireland incorporates both hospital and community-based training. The transition from hospital medicine to General Practice (GP) can be a challenging experience and research on this period in GP training is limited. This study provides insight into GP trainees' experience of this crucial professional transition.

Aim: The aim of this study was to explore GP Registrars’ experiences of moving from hospital medicine to General Practice.

Methods: This is a qualitative study. An initial in-person focus group was carried out with fourth year GP Registrars. The results of this focus group informed the development of a topic guide for subsequent one-to-one semi structured interviews with third- and fourth-year GP Registrars from thirteen GP Training Schemes nationally. 15 interviews in total were recorded, transcribed, and analysed. Data was analysed using reflexive thematic analysis (Braun and Clarke).

Results: The evolving role of the trainer in supporting the transition was highlighted, a. As was the trainers’ role in navigating clinical uncertainty and in shaping the participants’ professional identities.

Participants described the contributions of hospital rotations, scheme-directed teaching, and peer support, to the development of clinical confidence and autonomy. The nuances of challenges such as time pressure and increased clinical responsibility were discussed. These challenges were exacerbated by the pressure of clinical decision-making and a lack of confidence in applying this judgement in the community setting.

Conclusion: The results of this study will inform the development of improved structures to support GP trainees in their transition from hospital to community-based practice.

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Dysfunctional myelin worsens phosphorylated tau-induced pathologies in a mouse model of tauopathy Andrew Octavian Sasmita1,2*, Lina Komarek1*, Erinne Cherisse Ong1, Anne-Fleur Wildenburg1, Shuying Mao1, Sophie Siems1, Vasiliki-Ilya Gargareta1, Veronika Hantakova1, Constanze Depp1, Klaus-Armin Nave1 (* Equal contribution) 1. Department of Neurogenetics, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany 2. Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland Myelin is the insulating layer around axons in the nervous system, crucial for rapid action potential propagation and axonal support. Age-related myelin decline coincides with amyloid pathology in Alzheimer’s disease (AD). While we have shown that myelin dysfunction exacerbates amyloidosis, its impact on phosphorylated tau (p-tau) pathology, seen in p-tau neurofibrillary tangles in AD patients, is less understood. Using genetic mouse models of dysmyelination (Plp-/-) and tauopathy (PS19), we found that double mutants exhibited worse performance in behavioral tests, especially ones measuring anxiety, short-term memory, and motoric functions. These mice exhibited increased p-tau load, particularly in white matter tracts, and heightened gliosis. Interestingly, correlation analysis revealed that severe gliosis and not p-tau load is a stronger predictor of poorer behavioral outcomes.

We also observed elevated p-tau-bearing neurons in the spinal cord, linked to motoric deficits.

Interestingly, single Plp-/- mutants showed p-tau inclusions without human tau transgene induction, suggesting myelin dysfunction may lead to the generation of neuronal p-tau seeds. Furthermore, amyloid pathology in the 5xFAD mouse model of amyloidosis appeared to enhance p-tau inclusions in double Plp-/- 5xFAD mutants. Further biochemical characterization and analysis of myelin mutants' transcriptomic changes are needed to understand the mechanisms driving this disease exacerbation.

Taken together, our study provides the first in vivo evidence that myelin health perturbation, leading to axonal damage, worsens p-tau pathologies and behavior. This highlights myelin dysfunction as a risk factor for tau pathology in AD and other tauopathies, such as frontotemporal dementia.

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An Investigation into General Practitioners’ experience with Long Covid Aisling Farrell1, James O'Flynn1, Aisling Jennings2 1. Irish College of General Practitioners 2. Department of General Practice, University College Cork Background: Long Covid (LC) is the continuation or development of new symptoms after initial COVID19 infection. Little is known about General Practitioners’ (GP) experience of managing patients with LC. Aims: The aim of this study is to establish GP experiences with LC. Methods: A survey was designed and piloted in three training practices prior to distribution. The survey was completed by doctors working in GP training scheme practices in Cork, Ireland.

Results: 53 of 160 invited GPs completed the survey, indicating a 33% response rate. 8% (4/53) of participants agreed and 0% (0/53) strongly agreed with the statement they were “confident in diagnosing Long Covid”. 81% (43/53) were not confident in treating patients with LC. 70% (37/53) were unaware of indications for referral to secondary care. 38% (20/53) were aware of the referral pathway to local LC clinics. 93% (49/53) agreed there were educational deficits regarding LC. Conclusions: There was a lack of confidence in the diagnosis and management of LC, and in the interface with secondary care. There is demand for educational interventions to assist GPs with their care of patients with this emerging condition.

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SKOR1 as a potential therapeutic target in preventing α-synuclein-induced degeneration in models of Parkinson’s disease.

Lauren Barrett1*, Kieran McDermott2, Aideen M. Sullivan3, Louise M. Collins1,4, Gerard W. O’Keeffe1 1. Department of Anatomy & Neuroscience, School of Medicine, UCC, Cork, Ireland.

2. Graduate Entry Medical School, University of Limerick, Limerick, Ireland.

3. Department of Pharmacology & Therapeutics, School of Medicine, UCC, Cork, Ireland.

4. Department of Physiology, School of Medicine, UCC, Cork, Ireland.

Parkinson’s disease (PD) is a neurodegenerative disorder caused by degeneration of midbrain dopamine (mDA) neurons with reduced striatal dopamine and motor impairments. Given the lack of disease-modifying therapies, it is crucial to identify novel therapeutic targets for neuroprotection.

Microarray analysis revealed SKI Family Transcriptional Corepressor 1 (SKOR1) as the gene mostupregulated in the rat αSynuclein (αSyn) model of PD. SKOR1 overexpression was then shown to impair neurite growth, but it is unknown whether SKOR1 knockdown can protect against αSyn. To investigate this, we used SH-SY5Y cells, which are widely used in PD research. Cells were transfected at 24h post-plating with 10nM of small-interfering RNA (siRNA) against SKOR1, or 10nM scrambled siRNA (siSCR) as a control. Cells were co-transfected with 500ng of plasmid expressing either GFPtagged wild-type αSyn as a cellular model of PD, or GFP as a control. Cells were cultured for 72hrs before performing live imaging using an Olympus-IX71 inverted microscope to capture images of GFP+ neurites for neurite-length analysis. Culture media was collected to determine cellular cytotoxicity by measuring LDH release.

Significantly lower neurite length was found in cells transfected with αSyn, compared to controls (P<0.0001). Significantly higher neurite length was found in cells transfected with siSKOR1, compared to controls (P<0.01). Furthermore, siSKOR1 exerted a neuroprotective effect against αSyn-induced decreases in neurite length (p<0.001). Immunocytochemical staining confirmed that these differences in neurite growth were not secondary to differences in αSyn levels between groups. There were no significant differences in LDH release between groups, indicating that the differences in neurite growth were not secondary to differences in cell survival. These results highlight SKOR1 as a potential therapeutic target to ameliorate the negative impact of αSyn on neuronal integrity in PD.

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Assessing the Impact of a Tailored Educational Intervention to Improve Clinical Communication involving Adults with Age-Related Hearing Loss Imogen Lyons1, Aisling Maher1, Amr El Refaie2, Nicole Muller2, Brendan Lennon3, Susan Timmons1, Matthew Cronin1, Colm O Tuathaigh1 1. University College Cork, School of Medicine, Cork, Ireland, 2. University College Cork, School of Clinical Therapies, Cork, Ireland, 3. Chime, Chime, Dublin, Ireland Background: Age-related hearing loss (ARHL) significantly impacts communication and contributes to medical errors due to healthcare professional (HCP)–patient miscommunication. The 'BRIDGE' intervention, an online educational program for Irish hospital-based HCPs, was developed to address these communication barriers and improve health outcomes for adults with ARHL. Methods: The study involved three phases: Phase 1 developed the BRIDGE intervention through group concept mapping (GCM) with experts and older adults. Phase 2 implemented the intervention using a quasi-experimental pre-post design across three clinical settings, delivered via the Canvas platform.

Phase 3 evaluated outcomes using satisfaction measures, and assessments of HCP knowledge, attitudes, and behaviours, alongside patient-reported outcomes.

Findings: Phase 1 identified key areas for the BRIDGE program: HCP training, supports and assistive devices, environment, and clinician communication practices. The intervention, consisting of narrated explainer videos and multimedia resources, was deployed to HCPs. Data collection is ongoing, with expected results to include quantitative comparisons of pre- and post-intervention HCP knowledge and patient satisfaction.

Discussion: The BRIDGE intervention offers an innovative approach to improving HCP-patient communication in older adults with ARHL, aiming to enhance health outcomes and foster research collaboration.

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Influence of Capsule Size on Gastric Emptying of Enteric Capsugel® Enprotect® Capsules in Pigs Sophia V. Hoffmann1, Joseph P. O’Shea1, Vincent Jannin2, Brendan T. Griffin1 1. School of Pharmacy, University College Cork, College Road, Cork, Ireland 2. Capsugel France SAS, 68000 Colmar, France Reliable pre-clinical large animal models are vital during drug development to facilitate rational design of oral formulations that ensure optimal release and uptake in vivo. The anatomical and physiological parallels with humans make the pig model valuable in this respect [1]. A key drawback of this model is prolonged gastric emptying time compared to humans, particularly with non disintegrating formulations [1]. This limitation can potentially be addressed by administering prokinetic agents [1].

This study aimed to systematically assess how capsule size influences gastric emptying time of enteric capsules in the landrace pig model through pharmacokinetic analysis of rapidly absorbed marker compounds.

This study utilized a four-way crossover design in eight fasted landrace pigs to assess the gastric emptying rate of Capsugel® Enprotect® capsules (Sizes 0, 1 and 2) containing paracetamol. The effectiveness of intramuscular metoclopramide as a prokinetic agent was also evaluated. Immediate release caffeine tablets were used as a control.

Increased capsule size demonstrated slower gastric emptying times, as indicated by a higher tmax and lower AUC0-8h. In comparison, immediate-release caffeine tablets showed minimal delay in gastric emptying, though tmax appeared slower to that previously reported [1]. Intramuscular metoclopramide did not enhance rate nor consistency of gastric emptying, with apparent increased variability and tendency towards slower gastric emptying, as evidenced by changes in median tmax, cmax, and AUC0-8h.

[1] C. Suenderhauf et al., “Pharmacokinetics of paracetamol in Goettingen minipigs: In vivo studies and modeling to elucidate physiological determinants of absorption,” Pharm Res, vol. 31, no. 10, pp. 2696– 2707, 2014.

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A clustering-based methodology for cell-type deconvolution in spatial transcriptomic analysis Qingyue Wang1, Jian Huang1, Yudi Pawitan2, Trung Nghia Vu2 1. School of Mathematical Sciences, UCC 2. Department of Medical Epidemiology and Biostatistics, KI Spatial transcriptomics is a method to locate and measure gene expression on tissue slices. However, most current spatial transcriptomics technologies perform it on individual spots containing a mixture of cells, thus lacking cell composition information. In this study, we developed DECLUST, a clusterbased methodology for cell-type deconvolution in spatial transcriptomics. DECLUST clusters the spots to preserve the spatial structure of tissues and identifies the cell-type-specific markers from single-cell RNA sequencing for accurate deconvolution. We applied this method to multiple simulated breast cancer datasets, as well as to two real-world datasets: ovarian cancer and mouse brain. The results showed that DECLUST performs well against other existing methods in both robustness and accuracy.

In summary, DECLUST provides an effective and reliable model for efficiently identifying cell-type composition in spatial transcriptomics data.

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How reliable is assessment of children’s sentence comprehension using a selfdirected app? A comparison of supported versus independent use.

Pauline Frizelle1, Ana Buckley1, Darren Dahly2, Paul Fletcher1, Dorothy Bishop3, Cristina McKean4 1. Department of Speech and Hearing Sciences, School of Clinical Therapies, UCC 2. School of Public Health, UCC 3. Department of Experimental Psychology, University of Oxford 4. School of Education, Communication and Language Sciences, University of Newcastle Background: While most standardized assessments in the field of speech and language therapy are delivered in person, recently there has been a recognition of the advantage of computerized assessments (expedited somewhat by Covid-19). Computerized assessments that can be completed by children independently, offer further benefits, such as screening children at scale; identifying whole class progress; and allowing for test completion in different educational settings without significant levels of staff training.

Aim: This study aims to examine the feasibility of using the Test of Complex Syntax- Electronic (TECSE), as a self-directed app, to measure sentence comprehension in children aged 4 to 5 ½ years old; how testing apps might be adapted for effective independent use; and agreement levels between face-toface supported computerized and independent computerized testing with this cohort. The study also explores how young independent testing could be used reliably.

Method: A pilot study was completed with 4 to 4;06-year-old children, to determine the appropriate functional app features required to facilitate independent test completion. Qualitative information was collected on children’s level of independence; type of tester support required; and level of engagement. Test features were modified accordingly.

The main study was a within subject design whereby participants completed the TECS-E app twice (independently or with adult support) (4 - 4;05 (n = 22) 4;06 - 4;11 months (n = 55) 5 to 5;06 (n = 113)).

Test re-test reliability was examined.

Results: Qualitative observations, supported by statistical analyses indicated difficulties completing the test independently for the younger two cohorts. Pearson’s correlation indicated adequate test re-test reliability for children between 5 and 5;6 years (r = .71). A Bland -Altman analysis revealed a mean difference of -2.56 between scores in the supported versus independent test conditions. The rank ordering of children’s understanding of constructions was similar in both conditions.

Conclusion: Independent test completion posed problems for children under 5 years. However, children between 4;06 and 4;11 years understood the process more reliably than the younger cohort.

For children 5 years and over TECS-E, when used as a self-directed app, is a reliable method to assess children’s understanding of complex sentences.

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The understanding of complex syntax in children from 5-9 years, using a novel assessment approach - the Test of Complex Syntax- Electronic (TECS-E) Pauline Frizelle1, Ana Buckley1, Jorge Oliveira2, Paul Fletcher1, Dorothy Bishop3, Cristina McKean4 1. Department of Speech and Hearing Sciences, School of Clinical Therapies, UCC 2. School of Engineering and Architecture, UCC 3. Department of Experimental Psychology, University of Oxford 4. School of Education, Communication and Language Sciences, University of Newcastle Aim: This study aims to ascertain how well English speaking children (5-9 years) understand complex sentences; how type of construction, age, sex, and socio-economic status impact children’s performance; and the reliability/validity of the assessment tool.

Method: The TECS-E (a novel animated assessment method) was administered to over 900 Englishspeaking children, aged between 5;00 and 8;11 years, across the Republic of Ireland. The sample was further refined to 600 to ensure an accurate representation of the Irish population with respect to sex, socio-economic status, and locale. The validity and reliability of TECS-E was also estimated using testretest, concurrent validity and internal consistency measures.

Results: Children performed significantly differently on each family of constructions, (i.e. highest on relatives, lowest on adverbial clauses) with an upward trajectory from 5 to 9 years on all clause types.

Children from socially disadvantaged backgrounds scored significantly lower than those from more affluent backgrounds and females performed significantly higher than males. Differences associated with sex or background were no longer evident from 7 years. Results indicate high levels of internal and external reliability and a test-retest mean difference of agreement of -1.7.

Conclusion: This study contributes to our knowledge of typically developing children’s understanding of complex sentences from 5 – 9 years and shows that the TECS-E 1) can be reliably completed independently by children from 5 years; 2) has been norm referenced and standardised on a large and representative Irish population and 3) can be used to identify children’s strengths and weaknesses in understanding a range of complex sentences.

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The co-construction of a reading assessment checklist with adults with Down syndrome: a meaningful literacy approach.

Pauline Frizelle1, Sean O’Donovan1, Mary Jolley1, Lisa Martin2, Nicola Hart2 1. Department of Speech and Hearing Sciences, School of Clinical Therapies, UCC 2. Down Syndrome Ireland Aim: To co-construct a valid and reliable assessment measure that can be used to document meaningful everyday reading, in adolescents and adults with Down syndrome.

Methods: Stage 1 used an inclusive participatory design in which individuals with Down syndrome were research collaborators (n = 46). Items to be included in the measure were identified and ecological, face and content validity were established through an iterative process. In stage 2 we examined the reliability of the tool and explored potential relationships between meaningful reading score and (1) age, (2) receptive vocabulary, and (3) reading ability as measured by standardized assessments. In addition, we profiled what a pilot cohort of adults with Down syndrome read (n = 33) and how they experience reading in their everyday lives.

Results: Results showed that 46 items were generated for inclusion in the Meaningful Reading Measure (MRM). Preliminary data showed that the tool has internal and external reliability and ecological and content validity. No associations were evident between meaningful reading score and any other variable examined. There was considerable variability in items read (range 12–44) which reflected a broad range of reading practices. Adults with Down syndrome identified the importance of reading as a pleasurable activity and as something that aids learning.

Conclusion: The MRM can be used (1) as a reading intervention outcome measure to complement existing standardized tools, (2) to profile meaningful reading in adults with Down syndrome, (3) to guide reading module content, and (4) to capture change in adults’ perceptions of themselves as readers.

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The Ukrainian Experience of General Practice in Ireland Niall O'Reilly1, Eoin Murphy1, Emmet Smithwick1, Aisling A. Jennings2 1. GP Scheme Cork, 2. Dept of General Practice, UCC. Background: The war in Ukraine has led to an influx of Ukrainian refugees across Europe.

Internationally, there is limited research into refugees’ experiences of accessing Primary Care.

Furthermore, few studies have explored the experience of one homogenous refugee group. No study has explored the specific experience of Ukrainian refugees. To improve the care provided to this marginalised group it is important to understand the challenges they experience.

The aim of this research is to identify the barriers Ukrainian refugees experience when accessing General Practice in Ireland.

Methods: A 63-item questionnaire was distributed via Ukraine Action Ireland, a registered charitable organisation, to Ukrainian refugees in Ireland. Qualitive comments were collected through free-text responses and were analysed using thematic analysis.

Results: 368 questionnaires were completed. 75.4% of respondents reported that they were not asked about their mental health during consultations with their GP. 25% of respondents could not attend GP due to transport difficulties. 55% of respondents reported that a translator was needed but only one third of respondents reported that one was offered. Self-reported health was relatively poor when compared with refugees in other countries and with Irish citizens.

Three themes were developed; disparity in patient autonomy, perceived disregard for the refugee experience and challenges in health care access.

Conclusion: At a time of significant capacity challenges in General Practice it is paramount that resources are provided at a national level to address the challenges Ukrainian refuges currently experience.

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A Negative Experience: Exploring the Perspectives of Healthcare Assistants on Pain Management at End-of-Life for People Living with Dementia in a Nursing Home Brenda Au1 1. Centre for Gerontology and Rehabilitation, School of Medicine, College of Medicine and Health, University College Cork Background: End-of-life pain management for people living with dementia is challenging and recognizing pain in people who are often non-verbal is difficult. Most research on end-of-life pain management for people with dementia comes from the perspectives of nurses and physicians. While healthcare assistants in nursing homes in Ireland do not have a formal role in end-of-life pain management, they potentially are in a unique position to contribute to this because of the intimate knowledge they have of the person with dementia. This research differs in that it explores the perspectives of only healthcare assistants.

Methods: This qualitative study adopted a descriptive phenomenological approach. Semi-structured interviews were carried out with 11 healthcare assistants in a nursing home. Data was analyzed using an inductive thematic analysis approach.

Results: Caring for people with dementia at end-of-life evoked negative emotions in the healthcare assistants. Most of them perceived end-of-life pain management to be a negative experience; they played a limited role in this and felt overlooked. They felt pain management needed improving, and there was a lack of training in end-of-life care. Most healthcare assistants were confident they knew when people with dementia were in pain at end-of-life, were willing to attend further training, and all wanted to have a role in end-of-life pain management.

Conclusions: Healthcare assistants are potentially in a unique position to be trained to assess pain at end-of-life. However, more research is needed on effective ways to train them and on how to enhance their role and status.

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ATXN2 intermediate expansions in Amyotrophic Lateral Sclerosis affect neurofilament regulation and reveal new patterns in pathogenic markers Bastian Bues1,3, Vivian Dambeck2,3, Katie R. O’Mahony1, Suzy Varderidou-Minasian4, Mathias Bähr2,3, R. Jeroen Pasterkamp4 and Katja Burk1,2,3 1. School of Biochemistry and Cell Biology, University College Cork, Ireland 2. Department of Neurology, University Medical Center Göttingen, Germany 3. Center for Biostructural Imaging of Neurodegeneration (BIN), University Medical Center Göttingen, Germany 4. Department of Translational Neuroscience, University Medical Center Utrecht Brain Center, Utrecht University, The Netherlands Neurofilament defects are early pathogenic markers in both in familial and sporadic forms of Amyotrophic Lateral Sclerosis (ALS) and have been extensively studied over the past 40 years. The overall observations include accumulation and/or aggregation of neurofilaments and phosphorylated neurofilaments in the cell body and axons (showing as axonal spheroids) of motor neurons. However, despite these efforts, little is known about the mechanisms underlying these abnormalities.

In this project, we are using a set of newly generated iPSC-lines from ALS patients carrying Ataxin-2 (ATXN-2) intermediate-length polyQ expansions, a well-studied genetic risk factor in ALS. Importantly, ATXN-2 polyQ expansions are also found in patients carrying other ALS causing mutations such as in TDP-43, FUS and C9ORF72.

We report new findings on neurofilaments in ALS in the ATXN-2-ALS lines which contrast previously reported observations. First, we found a persistent downregulation of certain neurofilaments over time- both at the transcriptional and translational levels. Second, we report a shift of other neurofilaments into RIPA-insoluble fractions. Third, we found neurofilament-associated mechanistic defects of the endo-lysosomal system including changes in trafficking behaviour.

Since neurofilament abnormalities represent a point of convergence in both familial and sporadic forms of ALS, understanding neurofilament behaviour in ALS will help to shed light on shared mechanisms and may provide starting points for therapeutic intervention.

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Evaluating Adrenomedullin as a Target of Oral RNA-based Therapy for Ileal Crohn’s Disease Klara Martinović Mušić1,2,3, Ken Nally1,3, Silvia Melgar1 1. APC Microbiome Ireland, University College Cork 2. Department of Medicine, School of Medicine, University College Cork 3. School of Biochemistry and Cell Biology, University College Cork Adrenomedullin (AM) is a small hormone ubiquitously present in various tissues with multiple biological functions including vasodilation and angiogenesis. Recent studies have shown that AM also acts as a regulator of inflammation in inflammatory bowel disease (IBD). In murine models, adrenomedullin reduced inflammation, improved epithelial barrier and mucosal healing [1,2]. This data indicates AM is a potential therapeutic for Crohn’s disease, however, the mechanism(s) and intestinal cell types targeted by AM are yet to be uncovered. By using relevant cell culture models, we aim to identify mechanisms and which intestinal cell subsets are targeted by adrenomedullin. This work has been done in scope of the GENEGUT project which aims to develop a novel oral RNA-based treatment against ileal Crohn’s disease. To examine the effect of adrenomedullin we utilized human intestinal epithelial cell lines (Caco-2 and HT29), THP-1 derived macrophages and endothelial cells (HUVECs). We have optimized healthy and inflamed culture conditions to mimic the IBD-inflammatory environment. We have shown that, in the epithelial cell model of inflammation, adrenomedullin does not exhibit an anti-inflammatory effect and, in a barrier integrity model, it does not rescue barrier disruption. Adrenomedullin did not show a significant anti-inflammatory effect in activated macrophages or in endothelial cells (HUVECs). However, we have shown AM-peptide is bioactive and signals through cAMP/Phospho-AKT pathways in HUVECs. Overall, our data does not support adrenomedullin targeting inflammation or improving barrier function in these cell systems. Further studies will focus on more complex cell systems and/or preclinical models.

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Factors that Predispose Glioma Patients to Haematological Toxicity with Temozolomide: A Scoping Review Darren Crowley1, Maria Donovan1, Harriet Bennett-Lenane1, Brendan T. Griffin1, Jack P. Gleeson2 1. School of Pharmacy, University College Cork, Cork, Ireland.

2. Cancer Research @UCC, College of Medicine and Health, University College Cork, Cork, Ireland.

Glioblastoma multiforme (GBM) is a poor prognosis cancer, with studies suggesting that only 4% of patients survive beyond five years. Temozolomide (TMZ) is the current standard of care systemic treatment for GBM, which has shown a survival benefit for these patients. However, dose-limiting haematological toxicities necessitate treatment interruption or discontinuation for some patients. The objective of this scoping review is to identify factors that predispose individuals to haematological toxicity due to TMZ. Original research articles which included individuals being treated with TMZ (Population), in which factors which could predispose patients to haematological toxicity were analysed (Concept) in human studies (Context) were sought. A narrative synthesis of the results was conducted. A pooled proportions meta-analysis investigating the rates of toxicity between the concomitant and adjuvant phases of treatment was undertaken. The average rates of different dose limiting toxicities across the studies was calculated.

There were 60 eligible studies, with 50 different factors investigated within. Female gender, the concomitant phase of therapy, dose of 200mg/m2/day and generic TMZ formulations were the factors identified to be most predictive of haematological toxicity. From the results of the pooled proportions meta-analysis, it was identified that there is a significant increase in the rates of toxicity in the adjuvant phase of treatment.

Stemming from this identification of predictive factors for haematological toxicity, future studies can focus on managing the risk of haematological toxicity in these cohorts, using population pharmacokinetic modelling to individualise dosing or by implementing an enhanced monitoring schedule for at risk patients.

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Microbiome-related biomarkers for relapse prediction in treatment-naïve paediatric ulcerative colitis patients Maria Kulecka1, Jill O’Sullivan1,2, Rachel Fitzgerald1,2, Protima Deb3, Ian Sanderson4, Ana Velikonja1, Chloe Huseyin1, Emilio J Laserna-Mendieta1, Aldert Zomer5, Silvia Melgar1, Marcus Claesson1,2 1. APC Microbiome Ireland, University College Cork, T12 YT20 Cork, Ireland.

2. School of Microbiology, University College Cork, T12 YT20 Cork, Ireland.

3. Barts Health NHS Trust, The Royal London Hospital, London E1 1BB, UK 4. Queen Mary University of London, Blizard Institute, Centre for Immunobiology, 4 Newark Street, London E1 2AD, UK 5. Division of Infectious Diseases and Immunology, Utrecht University, Utrecht 3584 CL, the Netherlands Objective: This study aims to enhance treatment protocols for pediatric ulcerative colitis (UC), an inflammatory bowel disease, by identifying microbial biomarkers associated with relapse in treatmentnaive. Current first-line treatments, such as 5-ASA drugs and corticosteroids, are effective in only half of the patients. Identifying those at risk of relapse could enable early introduction of more aggressive treatments, like immunosuppressants.

Methods: Biopsies from 48 paediatric patients (2-16 years of age) were collected during colonoscopy.

Of these, 23 experienced relapse within 6 months (PUCAI 10+). Next-generation sequencing of V3-V4 hypervariable region and 16S qPCR provided data on relative and absolute bacterial abundances. Taxa differential abundance between relapse and remission groups was identified with zero-inflated Gaussian and negative binomial mixed-effect models. Meta-variables relevance to microbiome composition was assessed with VpThemAll package. XGBoost-based machine-learning models were used to predict relapse.

Results: Diversity and species richness were diminished in the relapse group. 23 and 10 differential taxa were differential in negative binomial and Gaussian models respectively. Differential taxa included probiotic bacteria (Bifidobacterium genus, elevated in remission group) and pro-inflammatory species (from Veilonella and Fusobacterium genus, elevated in relapse). Patient treatment status ranked as third most relevant variable in explaining variance in the microbiota. Models based on ascending colon samples microbiome and demographic data reach AUC above 0.7.

Conclusions: Gut microbial composition is linked to treatment response in paediatric UC. Differential taxa include probiotic bacteria (Bifidobacterium genus, elevated in remission group) and proinflammatory species (from Veilonella and Fusobacterium genus, elevated in relapse). Microbiomebased models achieve good performance in predicting relapse.

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The Idylla™ IDH1-2 Mutation Assay Kit demonstrates high sensitivity and specificity for detection of IDH mutational status in glioma.

Reiltin Werner1,2, Mairead Dorney1, Loëtitia Favre3, Riikka Mertaniemi4, Linea Melchior5, Salima Mrabet-Dahbi6, Alejandra Salas Diaz Daniela7,8,9, Natalia Shelestovich10, Hilla Tabibian-Keissar10, Cristina Teixido7,8,9, Suzanne Tran3, Sarah Truelsen5, Timo Vaïsänen11, Collette K Hand2, Louise Burke1,2, Michael Jansen1 1. Pathology Department, Cork University Hospital, Cork, Ireland.

2. Department of Pathology, School of Medicine, University College Cork, Cork, Ireland.

3. Neuropathology Department, hôpital de la Pitié Salpétrière, France.

4. Biochemical Laboratory Science, Oulu University of Applied Sciences, Oulu Finland.

5. Department of Pathology, Rigshospitalet, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark.

6. Institut für Pathologie - Klinikum Kassel, Kassel, Germany.

7. Department of Pathology & Molecular Biology CORE, Hospital Clinic of Barcelona, Barcelona, Spain.

8. Department of Medicine, University of Barcelona, Barcelona.

9. Translational Genomics and Targeted Therapies in Solid Tumors, August Pi I Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.

10. Department of Pathology, Sheba Medical Center, Israel.

11. Department of Pathology, Healthcare Support Service, Northern Ostrobothnia Wellbeing County, Oulu University Hospital, Oulu, Finland.

Introduction: With the evolution of precision medicine, IDH inhibitors are essential for managing glioma patients with targetable mutations. IDH1-2 have emerged as key diagnostic and prognostic markers in these malignant brain tumours. Thus, rapid assessment of IDH mutation status is necessary.

Methods: The Idylla™ IDH1-2 Mutation Assay Kit is a fully automated assay detecting five IDH1 mutations in codon R132, four IDH2 mutations in codon R140, and six IDH2 mutations in codon R172 within 95 minutes. Centres from Europe, US, Israel, and Thailand evaluated its performance in a global multicentre study using FFPE tissue samples and extracted DNA genomic material.

Results: Each centre tested 10-15 samples pre-analysed by routine reference technology (Immunohistochemistry, Next Generation Sequencing, or Polymerase Chain Reaction), with a final target of analysing 150 samples. Intermediate analysis, based on data from 7 out of the 13 centres, was conducted on 94 samples, comprising 69 FFPE tissue samples and 25 extracted DNA samples.

These samples encompassed 57 IDH1 mutations, 9 IDH2 mutations, and 28 samples without IDH1 or IDH2 mutations. The Idylla™ assay produced a valid result in 99% (93/94) of cases, demonstrating 98.5% sensitivity (65/66), 100% specificity (27/27), and an overall concordance rate of 98.9% (92/93).

Conclusion: The Idylla™ IDH1-2 Mutation Assay demonstrates high sensitivity and specificity in detecting IDH1-2 mutations in gliomas across real-world clinical settings. The rate of development of targeted treatments and biomarkers has led to increased demand for rapid results in the clinical diagnostic laboratory. This system is easily integrated into pathology laboratories, facilitating fast turnaround time of IDH1-2 results to clinicians. The implementation of this time-saving assay with minimal hands-on time and easily interpretable report will enhance cancer care for glioma patients.

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Implementation of an ISO 15189 Accredited Next Generation Sequencing (NGS) Service for Cell-Free Total Nucleic Acid (cfTNA) Analysis to Facilitate Driver Mutation Reporting in Plasma.

R. Werner1,2, R. Crosbie1, A. Connolly1, M. Dorney1, M. Jump1, D. Collins3, C. K. Hand2, L. Burke1,2 1. Pathology Department, Cork University Hospital, Cork, Ireland 2. Department of Pathology, School of Medicine, University College Cork, Cork, Ireland 3. Medical Oncology Department, Cork University Hospital, Cork, Ireland Introduction: Next Generation Sequencing (NGS) on tumour tissue is integral to the delivery of personalised medicine and targeted therapy. NGS on liquid biopsy, a much less invasive technology, is an emerging clinical tool that has a rapidly expanding clinical utility. Gene mutations in cell-free Total Nucleic Acids (cfTNA) circulating in the blood are representative of whole tumour biology and can reveal different mutations from different tumour sites, thus addressing tumour heterogeneity challenges.

Methods: The novel Ion Torrent Genexus NGS with automated sample preparation, on-board library preparation, templating, sequencing, data analysis, and Oncomine Reporter software was utilised. cfTNA extracted from plasma was verified with the targeted pan-cancer (~50 genes) Oncomine Precision Assay (OPA). Assessment criteria included analytical sensitivity, specificity, limit of detection (LOD), accuracy, repeatability, reproducibility, and the establishment of performance metrics.

Results: An ISO 15189 accredited, minimally invasive, cfTNA NGS diagnostic service has been implemented. High sensitivity (>83%) and specificity between plasma and tissue was observed.

Sequencing limit of detection (LOD) of 1.2% was achieved when depth of coverage is >22,000x. NGS of cfTNA in plasma attained ISO15189 accreditation. A significant reduction (>68%) in turnaround time (TAT) of liquid biopsy results was achieved; 5 days TAT for in-house analysis from sample receipt to final report issued to oncologist as compared to >15 days from reference laboratories.

Conclusion: Tumour derived somatic variants (~50 gene panel) can now be reliably assessed from plasma to provide minimally invasive tumour profiling. Successful implementation of this ISO15189 accredited service resulted in: • Appropriate molecular profiling of patients where tumour tissue is unavailable or inaccessible.

• Rapid TAT of NGS results to oncologists.

• Capturing potential cases of tumour heterogeneity.

• Timely switching of therapy at progression following the detection of resistance mutations via simple blood plasma sample.

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Prescribing cascades among older community-dwelling adults in Ireland: prescription sequence symmetry analysis of ThinkCascades in a national dispensed prescription database.

Ann Sinéad Doherty1, Lars Christian Lund2, Frank Moriarty3, Fiona Boland4, Barbara Clyne5, Tom Fahey6, Denis O’ Mahony7,8, Seán P Kennelly8,9, Emma Wallace1 1. Department of General Practice, School of Medicine, UCC, Ireland.

2. Clinical Pharmacology, Pharmacy and Environmental Medicine, Institute of Public Health, University of Southern Denmark, Odense, Denmark.

3. School of Pharmacy and Biomolecular Sciences, RCSI University of Medicine and Health Sciences, Dublin 2, Ireland.

4. Data Science Centre, RCSI University of Medicine and Health Sciences, Dublin, Ireland.

5. Department of Public Health and Epidemiology, School of Population Health, Royal College of Surgeons (RCSI) University of Medicine and Health Sciences, Dublin, Ireland.

6. Department of General Practice, Royal College of Surgeons in Ireland (RCSI) University of Medicine and Health Sciences, Dublin, Ireland.

7. Department of Medicine (Geriatrics), School of Medicine, University College Cork, Cork, Ireland.

8. Geriatric Medicine, Cork University Hospital, Cork, Ireland.

9. Department of Age-related Healthcare, Tallaght University Hospital, Dublin, Ireland.

10. Department of Medical Gerontology, School of Medicine, Trinity College Dublin, Dublin, Ireland.

Introduction: Prescribing cascades occur when medication is used to treat side-effects of another medication, with older polypharmacy-exposed adults at higher risk.

Aim: This study examined the prevalence, magnitude, and effect modification of nine prescribing cascades (ThinkCascades list) in a national prescription database.

Method: Prescription sequence symmetry analysis (PSSA) was applied to primary care prescriptions for ThinkCascades medications dispensed under the General Medical Services (GMS) scheme from 2017 to 2020 (n=533,464). Incident users of both medications in each ThinkCascades dyad aged ≥65 years were included. A one-year run-in period defined incident use. An observation window of 365 days was employed; varying windows were examined in sensitivity analyses. Sequence ratios were adjusted for secular prescribing trends (aSR). Stratified analyses were conducted for sex, age, and individual medication.

Result: Five prescribing cascades produced significant positive aSRs. The strongest signal was identified for the calcium channel blocker to diuretic cascade (aSR 1.93, 95%CI 1.79, 2.09). Positive signals were also identified for the alpha-1 receptor blocker to vestibular sedative (aSR 1.63, 95%CI 1.46, 1.81); SSRI/SNRI to sleep medication (aSR 1.54, 95%CI 1.40, 1.69); antipsychotic to antiparkinsonian (aSR 1.20, 95%CI 1.00, 1.43); and benzodiazepine to antipsychotic (aSR 1.15, 95%CI 1.08, 1.21) cascades.

Discussion: Five prescribing cascades for commonly prescribed medications were identified in a largescale national sample of older Irish adults. This study highlights prescribing cascades as an important contributor to complex polypharmacy for older people. Adverse drug reactions should be included in the differential diagnosis for older adults presenting with new symptoms in primary care.

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Investigation of the impact of experimental Traumatic Brain Injury on acute changes in immuno-metabolism gene expression in the mouse cortex and hippocampus.

Susan C. Burke1, Yvonne M. Nolan1,2, Harriet Schellekens1,2, Rebecca J. Henry1 1. Department of Anatomy and Neuroscience, School of Medicine, University College Cork, Cork, Ireland 2. APC Microbiome Ireland, University College Cork, Cork, Ireland Introduction: Neuroinflammation is a key secondary injury mechanism following exposure to traumatic brain injury (TBI). Evidence suggests that shifts in intracellular metabolic processes (oxidative phosphorylation → glycolysis) drives pro-inflammatory responses in the brain microenvironment.

Thus, the aim of the present study was to examine acute changes in expression of inflammatory and metabolic genes in the cortex and hippocampus following exposure to TBI. Methodology: Adult male C57BL/6 mice (n=5) underwent either moderate level controlled cortical impact (CCI) or sham surgery. Mice were euthanised at 7 days post injury (dpi) and ipsilateral cortical and hippocampal tissue was processed for mRNA analysis. Statistical analysis was preformed using an unpaired Student’s t-test.

Results: TBI resulted in a significant increase in cortical expression of the pro-inflammatory mediators NLRP3 (p<0.01), IL-1β (p<0.01), TNF-α (p<0.001), NOX-2 (p<0.05), and p22phox (p<0.01), when compared to sham operated counterparts. Similar effects were reported in the hippocampus including significant TBI-induced increases in NLRP3 (p<0.01), IL-1β (p<0.001), TNF-α (p<0.0001), NOX-2 (p<0.05), and p22phox (p<0.01). In addition, TBI resulted in a significant increase in both cortical (p<0.05) and hippocampal (p<0.001) expression of the microglial marker, CD11b, when compared to sham counterparts. TBI resulted in a significant increase in cortical (p<0.001) and hippocampal (p<0.0001) expression of the master regulator of glycolysis, PFKFB3. Furthermore, TBI resulted in a significant increase in hippocampal (p<0.01), but not cortical expression of PFKFB1. Finally, TBI did not significantly alter gene expression of markers associated with oxidative phosphorylation including PGC1α and SIRT-1 in the cortex or hippocampus.

Conclusions: Exposure to TBI results in acute increases in cortical and hippocampal pro-inflammatory gene expression and select markers of glycolytic metabolism. Developing our understanding of immuno-metabolic responses following exposure to TBI may offer novel insights into therapeutic targets.

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PEGDM and nHA-PEGDM Hydrogels for Biomedical Applications Sabrina Alom1, Rasha Alshaikh2, Katie Ryan2, Rekha Gautam1, Kiang Wei Kho1, Stefan AnderssonEngels1,3, Imanda Jayawardena1 1. Tyndall National Institute, Cork, Ireland 2. School of Pharmacy, University College Cork, Ireland 3. School of Physics, University College Cork, Ireland Background & Aims: Biomedical technology is increasingly dependent on new materials which can support and enhance the body's natural healing processes. Hydrogels such as Poly(ethylene glycol) dimethacrylate (PEGDM) have emerged as a biocompatible material with tunable mechanical properties and extracellular matrix mimetics. Biological activity and mechanical strength can be further improved with the incorporation of nano hydroxyapatite (nHA) to the PEGDM hydrogels. These hydrogels are suitable for biomedical applications, including tissue engineering and drug delivery systems. This preliminary study aims to fabricate, characterise and optimise PEGDM and nHA-PEGDM hydrogels for biomedical applications.

Methods & Results: Various concentrations of PEGDM and nHA PEGDM hydrogels were prepared and their properties were evaluated. Cryo-SEM enabled high resolution images revealed the hydrogel morphology and microstructure. Cell culture experiments using Human Umbilical Vein Endothelial Cells (HUVEC) assessed preliminary cell viability. A certain degree of initial cell viability followed a decline in cell viability, owing to poor cell adhesion, which is to be optimised. Raman spectroscopy identified chemical signatures of PEGDM which varied with concentration. It further indicated an increase in the characteristic 960cm-1 peak as nHA content was increased, while hydrogel peaks remained constant. Mechanical testing was performed to evaluate load-bearing capacity, and indicated changes in the brittleness of the hydrogels with changing polymer and nHA concentrations.

Conclusions: Preliminary investigations on PEGDM and nHA PEGDM hydrogels demonstrated promising suitability as a biocompatible material that could be utilised in biomedical applications with required research optimisations.

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Oral care for post-stroke inpatients with dysphagia – a systematic review.

Claire Curtin1, Niamh Coffey2, Francis M. Burke1, Gerald McKenna3, Martina Hayes4 1. University Dental School & Hospital, UCC 2. Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 3. Centre for Public Health, Queen’s University Belfast, Belfast 4. Dublin Dental University Hospital, Dublin Background: Dysphagia is a common complication of stroke. It is recognised that oral care for patients with dysphagia is an important part of post-stroke care and rehabilitation however there are a lack of evidence-based guidelines available to inform the provision of oral care to patients experiencing dysphagia post-stroke.

Objectives: The objective of this study was to identify and critically evaluate the published literature on the effectiveness of oral care interventions for post-stroke inpatients with dysphagia. This study was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines and was registered on INPLASY ® (Registration no: INPLASY202470050).

Methods: Searches were conducted in the following electronic databases: Scopus, MEDLINE via Ebsco, Embase, CINAHL Plus and Web of Science (Core Collection). An assessment of the risk of bias of included studies was carried out using the Risk of Bias 2 (RoB 2) tool.

Results: The search of databases yielded 676 studies. The full text of seven studies were retrieved and four studies were included in the final analysis.

Discussion: Health professional led enhanced oral care interventions may improve the oral health and reduce the incidence of x-ray verified pneumonia of inpatients post stroke with dysphagia. There is, however, a lack of high-quality published research in this area and significant heterogeneity in methods, intervention, outcome measures and follow-up time across all published studies. More research is needed to investigate health professional-related outcomes, patient acceptability, coproduction and the role of the wider stroke multidisciplinary team in oral care.

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Exploring the Impact of LRRK2 Genetic Mutations on Cellular Susceptibility to Pesticides as a Risk Factor for Parkinson’s Disease Rachel Roberts1,2, Fionnuala E. Wilson1,2, Martina Mazzocchi2, Louise M. Collins2,3,4, Gerard W. O’Keeffe2,4, Aideen M Sullivan1,4 1. Department of Pharmacology & Therapeutics, School of Medicine, University College Cork 2. Department of Anatomy & Neuroscience, School of Medicine, University College Cork 3. Department of Physiology, School of Medicine, University College Cork 4. Parkinson’s Disease Research Cluster (PDRC), University College Cork Parkinson’s disease (PD) is a neurodegenerative disease affecting >10 million people. PD is defined by progressive degeneration of midbrain dopaminergic neurons, resulting in a range of motor and nonmotor symptoms. PD usually develops sporadically, but ~5% of cases are familial. Leucine-rich-repeatkinase-2 (LRRK2) mutations are the most common genetic cause. PD risk is thought to be determined by interactions between genetics and environmental factors, eg. pesticide exposure.

This study explored synergistic effects of G2019S-LRRK2 mutation and exposure to the pesticide rotenone, on cell viability and neurite outgrowth in SH-SY5Y cells, a common cellular model of PD. Treatment with 10uM or 1uM rotenone for 72h significantly reduced cell viability (measured by MTT assay) by ~85% and 40% respectively, compared with controls. Neurite outgrowth was reduced by ~65% and ~40% by 10uM and 1uM rotenone respectively.

Neurite length was significantly lower in SH-SY5Y cells overexpressing wild-type-(WT)-LRRK2 or G2019S-LRRK2 than in controls, showing that overexpression of either WT or mutant LRRK2 impaired neurite outgrowth.

Rotenone treatment of cells overexpressing WT-LRRK2 or G2019S-LRRK2 induced significant reductions in neurite length at doses lower (0.01uM, 0.1uM) than those needed to impair neurite outgrowth in controls, showing that LRRK2 mutations enhanced susceptibility to rotenone. Cell viability of transfected SH-SY5Y cells was significantly reduced by 1uM rotenone, to a greater extent than non-transfected cells, suggesting that the mutations increased susceptibility to rotenone.

These data show a key role of LRRK2 in mediating neuronal survival and neurite health, in the context of exposure to rotenone, a pesticide linked to PD.

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Exposure to serum from biologically stressed pregnant women decreases neurite length in SH-SY5Y cells through a tumour necrosis factor-α-dependent mechanism C. Deady 1,2, L. Wilmes1,2,3, F.P. McCarthy4,5, G. Clarke1,3,5, J. Keane2, C.M. McCarthy6, G.W. O’Keeffe1,2,5, S.M. O’Mahony1,2 1. Department of Anatomy and Neuroscience, School of Medicine, University College Cork, Cork, Ireland 2. APC Microbiome Ireland, University College Cork, Cork, Ireland 3. Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland 4. Department of Obstetrics and Gynecology, University College Cork, Cork, Ireland 5. The Infant Research Centre, University College Cork, Cork, Ireland 6. Department of Pharmacology & Therapeutics, University College Cork, Cork, Ireland Prenatal stress has long been associated with deleterious neurodevelopmental consequences in affected offspring, such as intellectual disability and behavioural disorders. Maternal immune activation, one category of prenatal stress, has been linked with various neurodevelopmental disorders and this increased risk may be due to circulating factors in the maternal blood, such as interleukin-6 (IL-6) and tumour necrosis factor-α (TNFα) on the basis that they may induce an inflammatory state in the foetal brain or placenta.

The Screening for Pregnancy Endpoints (SCOPE) study took place in Cork, Ireland from 2004-2011, and aimed to identify biomarkers that could be used to predict pregnancy outcomes. A subgroup of these women (n=104) was randomly selected from SCOPE and certain circulating factors in maternal plasma from gestational week 20 were quantified as described previously [1]. Tryptophan and its metabolite kynurenine, measures of gut permeability; intestinal fatty-acid binding protein, soluble CD14, lipopolysaccharide binding protein, and measures of inflammation; C-reactive protein, IL-6, and TNFα were used to compute a Z-score. Following the assignment of scores, those receiving the highest scores were labelled as ‘high stress’ (n=10), and the lowest scores as ‘low stress’ (n=10). SH-SY5Y cells were treated with 3% v/v low/high stress serum at 1 day in vitro and neurite length measured 72 hours posttreatment, fixed with 4% paraformaldehyde, before being immunocytochemically stained for β-III tubulin.

Treatment with the high stress serum significantly reduced neurite length in SH-SY5Y cells but did not affect overall cell viability or the expression of β-III tubulin. Blocking the functional activity of TNFα did not alter neurite length in the low stress group, but significantly prevented the reduction in neurite length seen in the previous experiment. A significant increase in NF-κΒ p65 expression was observed SH-SY5Y cells following exposure to high stress serum when compared to low stress serum.

Pregnant women were profiled into low or high stress groups dependent upon circulating immune and metabolic factors in their blood. Exposure to this serum reduced neurite length in SH-SY5Y cells, TNFα was found to be a significant contributor to this via increased phosphorylation of the NF-κΒ p65 subunit.

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The Maternal Gut Microbiota Modulates Neurodevelopment Through Regulation of The Blood-Cerebrospinal Fluid Barrier Permeability.

Jennifer Morael1,2, Hugo J. Blair1,2, Valentine Turpin1,2, Lorena Morales1,2, Alexandre J. C. Cergneux1,2, Anna Ratsika1,2, Emily G. Knox1,2, Jennifer Shearer1,2, John F. Cryan1,2, Maria R. Aburto1,2 1. Department of Anatomy & Neuroscience, School of Medicine and Health, University College Cork 2. APC Microbiome Ireland, Cork Throughout perinatal life, the maternal gut microbiome plays a crucial role in shaping offspring development. Maternal microbial signals are transmitted to the offspring via systemic circulation during gestation, vaginal birth, and skin-to-skin contact. These signals have been shown to play a role in neurodevelopment, though the specific mechanisms involved are not well understood.

The choroid plexuses (ChP), situated within the brain ventricles, is crucial to neurodevelopment, during which it regulates the permeability of the blood-cerebrospinal fluid barrier (BCSFB), a structure that tightly controls exchanges between the blood and cerebrospinal fluid (CSF). During early life, molecules within the CSF, including trophic and immune factors, signal to neural progenitors, influencing their proliferation, differentiation, and migration. Consequently, maintaining proper CSF homeostasis is essential for a healthy neurodevelopmental trajectory.

We hypothesize that maternal microbial signals modulate BCSFB permeability and immune environment of the ChP, leading to alterations in CSF composition that may disrupt normal neurodevelopmental processes.

To test this hypothesis, we analysed the effects of two types of maternal microbiota disruptions in mice on BCSFB integrity: antibiotic exposure during pregnancy and caesarean sections at birth. We assessed barrier integrity by analysing tight junction networks and evaluated the functional permeability of the BCSFB by injecting a fluorescent tracer into embryos and pups. Additionally, flow cytometry and immunohistochemistry were employed to characterize immune cell populations at the BCSFB. Our study shows significant evidence that the maternal gut microbiota modulates ChP integrity during the perinatal period, underscoring the role of the maternal microbiome in modulating brain development.

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Pharmacist Roles In Delivering Cardiac Rehabilitation: A Scoping Review Of The International Literature Sheesa Joseph1, Margaret Bermingham1, Sonia Akther1, Edel Burton1,2,3 1. Pharmaceutical Care Research Group, School of Pharmacy, University College Cork, Ireland 2. School of Public Health, University College Cork, Ireland 3. Pharmacy Department, Bons Secours Hospital Cork, Ireland Introduction: Cardiovascular disease (CVD) is a leading cause of global morbidity and mortality, necessitating effective secondary prevention strategies. Cardiac rehabilitation (CR) delivered by a multidisciplinary team (MDT) is essential in this context. Pharmacists, as MDT members, significantly reduce CVD risk factors and optimize pharmacotherapy, but their specific roles within CR are unclear.

This scoping review aims to explore the diverse roles of hospital pharmacists in outpatient CR by synthesising international literature.

Methods: This review follows the Joanna Briggs Institute (JBI) methodology for scoping reviews.

Systematic searches were conducted in three databases: CINAHL, SCOPUS, and MEDLINE, covering publications from database inception until March 5, 2024. English-language studies detailing hospital pharmacist involvement in CR were included, excluding those without a description of the pharmacist’s role or focused on inpatient settings. Two reviewers independently screened titles, abstracts, and full texts, with thematic analysis conducted to identify pharmacist roles. Results were reported according to the PRISMA-ScR guidelines.

Results: Out of 428 records, seven studies from; Canada, Egypt, Malaysia, the USA, and the UK were included. Six studies were quantitative, and one was qualitative, with sample sizes ranging from 40 to 316 patients and follow-up periods from 3 to 27 months. Pharmacists' roles, including patient education, medication management, drug-related problem resolution, and lifestyle management, were identified.

Conclusions: Hospital pharmacists in CR services perform roles from traditional medication management to more individualized, patient-oriented approaches. However, research on pharmacists' roles in CR is limited, highlighting the need for further studies to define and expand these roles.

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Comparing Compliance Levels of Regular and “As Required” Prescription Orders in an Irish Teaching Hospital: A Clinical Audit Aisling McDonald1,2, Emma Crowley1,3, Leah Walshe1,3, Susanne O’Shea1, Edel Burton1,3, Paul Gallagher4 1. Pharmacy Department, Bon Secours Hospital, Cork, Ireland 2. School of Medicine, University College Cork, Cork, Ireland 3. Pharmaceutical Care Research Group, School of Pharmacy, University College Cork, Cork, Ireland 4. Department of Geriatrics, Bon Secours Hospital Cork, Ireland Introduction: Illegible or incomplete prescription orders can delay medication dispensing and increase healthcare staff workload, particularly in Ireland, where handwritten drug kardexes are used. Such errors can compromise patient safety, leading to adverse drug events and increased healthcare costs. This study compared compliance levels of regular and "as required" prescription orders for adult inpatients in an Irish teaching hospital with Joint Commission International Standard MMU 4.2.

Methods: A cross-sectional clinical audit was conducted from September to November 2023, reviewing 50 randomly selected inpatient charts from five wards (two medical, two surgical, and one oncology). The audit evaluated the legibility and completeness of both regular and "as required" (PRN) medication orders. Completeness was defined as including drug name, dosage, frequency, and route of administration, with PRN orders also requiring an indication and maximum dosage within 24 hours. Descriptive statistics were conducted.

Results: The median patient age was 75 (SD=15.4) years, with 64% (n=38) being female. The mean number of total medications per patient was 11.8 (SD = 4.6), with a mean of 6.1 (SD = 3.8) for regular and 3.7 (SD = 2.5) for PRN medications. Of the 403 regular medication orders, 177 (43.9%) were complete, while only 25 (13.4%) of the 187 PRN orders were complete (p<0.001). Whereas, 96.3% (388) of regular medication orders were legible, with 94.7% (177) of prn orders legible.

Conclusions: Compliance was significantly higher for regular prescriptions than PRN orders, highlighting the need for continued targeted audits and education to improve prescribing practices and patient safety.

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Death Investigation and Certification During the COVID-19 Pandemic in Ireland: Retrospective Review to Inform Responses to Future Pandemics Sarah Ni Mhaolcatha1,2, Eleanor Fitzgerald3, Aurelie Fabre4, Mary Horgan5, Linda Mulligan6, Margot Bolster1,6, Collette Hand1, Louise Burke1,2.

1. Department of Pathology, School of Medicine, University College Cork 2. Department of Pathology, Cork University Hospital 3. The Coroners Society of Ireland 4. Department of Pathology, St. Vincent's University Hospital / University College Dublin 5. Chief Medical Officer, Department of Health / Mater Misericordiae Hospital / University College Dublin 6. Office of the State Pathologist, Department of Justice / University College Dublin Background: In Ireland, all deaths due wholly or partly to COVID-19 must be reported to the coroner.

Given the rapidly changing environment due to this novel pathogen we conducted a study to critically review how Ireland investigated and certified COVID-19 related deaths.

Design: A survey of the coroners was devised to collect qualitative data regarding their experience during the pandemic. Areas of analysis included: the role of guidelines for death certification, how deaths were investigated, the impact on mortality figures and recommendations for optimal management of future pandemics.

Results: Responses were received from 51% of coronial districts. National guidelines, developed with reference to best international practice, were widely adopted following their introduction in April 2020. Following implementation of guidelines, confidence in certifying a COVID-19 death increased from 74% to 95%. Overall, 95% agreed that unified national guidance improved the quality of death certification and recommended earlier publication and implementation.

Appropriate post-mortem examination (PME) facilities affected rates of autopsy. 32% of respondents indicated that appropriate PME facilities were not easily accessible. 57% reported that this inaccessibility to facilities impacted negatively on their decision to direct a PME on these cases. Overall, 57% of coroners believed that COVID-19 mortality figures derived from death certification is a true reflection of COVID-19 deaths.

Conclusion: Developing a blueprint for death investigation and certification in future pandemics caused by novel pathogens would enable a faster, effective, and coordinated response from all stakeholders, the pace of which is critical to inform important early-stage public health policy making.

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An audit examining the compliance of ‘as required’ prescription orders to hospital prescribing standards for adult inpatients of an Irish teaching hospital.

Aisling McDonald1,2, Susanne O’Shea1, Edel Burton2,3, Paul Gallagher1 1. School of Medicine, University College Cork, Cork, Ireland 2. Pharmacy Department, Bons Secours Hospital, Cork, Ireland 3. Pharmaceutical Care Research Group, School of Pharmacy, University College Cork, Cork, Ireland An audit examining the compliance of ‘as required’ prescription orders to hospital prescribing standards for adult inpatients of an Irish teaching hospital.

Introduction: Illegible and incomplete prescription orders can be a source of medication error for hospital inpatients. To improve patient safety, hospitals establish prescribing standards to define the required criteria of a legible and complete prescription order.

Aim: To evaluate the compliance of 'as required' prescription orders in an Irish teaching hospital against the Joint Commission International (JCI) Standard MMU 4.2.

Method: A clinical audit, in the form of a cross-sectional chart review, was conducted from September to November 2023. Fifty charts of inpatients aged ≥18 years were randomly selected from five wards.

‘As required’ prescription orders were analysed with the primary outcome measure being the level of compliance to the JCI Standard MMU 4.2 in terms of legibility and completeness criteria. A Plan-DoStudy Act (PDSA) cycle was conducted; which included a targeted educational intervention for prescribers. A reaudit of ten charts was performed three months post-intervention. Descriptive statistics were conducted.

Results: 187 ‘as required’ prescription orders were analysed. Of these, 177 (94.7%) were deemed legible, while only 25 (13.4%) were considered complete. Of the ten criteria for a ‘complete’ prescription order; three key areas of poor compliance were identified: the inclusion of ‘time’(n=80, 42.8%), ‘maximum dose’ (n=28, 15%), and ‘indication for use’ (n=43, 23%). Post-intervention, a reaudit of 42 ‘as required’ prescription orders demonstrated improvements in legibility(+5.3%) and completeness (+24.7%); with notable improvements in 'time' (+19.1%), 'maximum dose'(+37.8%), and 'indication for use'(+34.1%).

Conclusion: These findings emphasise the importance of continued audit and education to optimise prescribing practices, enhancing patient care and safety outcomes. As compliance remains below 100%, further investigation into factors affecting compliance is warranted.

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Breastfeeding and parental cardiometabolic risk: a prospective cohort study comparing maternal and paternal associations in mid-life.

Ferdous F.1, O’Neill K.N.1, O’Keeffe L.M.1,2,3, Rebecca Hardy4,5, Abi Fraser3, Laura D. Howe3, George Davey Smith2,3, Patricia M. Kearney1 1. School of Public Health, University College Cork, Cork, Ireland 2. MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom 3. Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom 4. Social Research Institute, University College London, London, UK 5. School of Sport, Exercise, and Health Sciences, Loughborough University, Loughborough, UK Introduction: Elaborating the concept of maternal and partner comparisons for intrauterine exposures, we use the maternal-partner comparisons method to explore the possibility of residual confounding of maternal breastfeeding and mid-life CVD associations by unmeasured or poorly measured sociodemographic characteristics.

Methods: Data were from 3210 mothers and 1407 partners of the Avon Longitudinal Study of Parents and Children (ALSPAC), a population-based birth cohort study which recruited 14,541 pregnancies to women resident in the Southwest of England. Linear regression analyses were used examine and compare associations of duration of any breastfeeding and duration of exclusive breastfeeding with traits in mid-life in mothers and partners.

Results: Duration of any breastfeeding was associated with lower concentrations of all VLDL, all triglycerides, VLDL particle size, glycoprotein acetyls, and glucose; and associated with higher concentration of HDL and LDL cholesterol, apolipoprotein B particle size in women. Among partners, there was no evidence of strong associations with any cholesterol, triglyceride, or glycaemic traits. For instance, compared with no breastfeeding, ≥9-months of any breastfeeding was associated with 0.25SD [-0.38 to -0.12] lower total triglyceride concentrations in mothers at age 47.9-y and 0.11SD [0.31 to 0.09] in partners at 50.8-y. Both exclusive, and any other breastfeeding were also associated with improved VLDL, and triglycerides concentrations in women compared with no breastfeeding group but in their partners, no such association was observed.

Conclusion: Findings provide some support for causality of breastfeeding with cardiometabolic traits in women in mid-life, though associations in are weak and may be of limited clinical significance.

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A patient satisfaction survey for a movement disorder clinic at St. Finbarr's.

Mahi M. Bhandarkar1 1. School of Medicine, UCC Background: Patient satisfaction is a critical metric for evaluating healthcare quality, especially in specialised clinics like the Movement Disorder Clinic (MDC) at St. Finbarr's Assessment and Treatment Centre (ATC). As Parkinson’s Disease and movement disorders need multidisciplinary care, understanding patient experiences is important for improving services at the clinic.

Aim: The study aspired to assess overall patient satisfaction at the MDC, focusing on aspects like accessibility, quality of care, and overall patient experience. It aimed to identify key factors of satisfaction, including waiting times and interactions with clinic staff and healthcare professionals, and to offer recommendations for improvement of the service.

Methods: A cross-sectional survey with a mixed-methods approach was performed. Surveys were distributed among patients (n=30) attending the MDC between February and June 2024. Data were analysed using descriptive statistics and thematic analysis to identify patterns and insights.

Results: The study found increased overall satisfaction with the MDC's services, particularly with the care provided by the consultant. However, issues were raised concerning waiting times and parking accessibility. The overall satisfaction levels varied by demographic factors, with the older group of patients and those with prolonged duration of PD expressing more concerns about logistical aspects.

Conclusion: While the MDC at St. Finbarr’s ATC is greatly valued for its quality care, especially by the consultant and other healthcare professionals, there are significant opportunities for improvement in areas such as waiting times, accessibility, communication and resource allocation. Addressing these challenges could further improve patient satisfaction and ensure the clinic prevails in delivering highquality, patient-centred care.

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Impact of Staff Turnover on Implementation of Infection Prevention and Control in Nursing Homes.

Majella Bradley1 1. School of Public Health, UCC Background: Staff turnover in nursing homes significantly impacts infection prevention and control effectiveness. The systematic review examined the relationship between staff turnover and IPC, highlighting key challenges and strategies for improvement.

Methods: A comprehensive literature search across multiple databases, covering studies from January 2010 to July 2024, was conducted. The Joanna Briggs Institute Mixed Methods Systematic Review approach was used, integrating qualitative and quantitative findings. Eight studies met the inclusion criteria, including three qualitative, four quantitative, and one mixed-method study.

Results: Three key themes emerged: staffing instability, training and knowledge of IPC practices, and nursing leadership. High staff turnover was consistently linked to increased infection rates and IPCrelated citations, largely due to disruptions in care continuity and training. The COVID-19 pandemic further exacerbated gaps in IPC knowledge and practice. However, strong, stable nursing leadership mitigated some of these negative impacts.

Conclusions: Addressing staff turnover is critical for improving IPC effectiveness in NHs. Strategies focused on staff retention, continuous training, and stable leadership are essential. These findings are especially relevant in the Irish context, where similar challenges exist, underscoring the need for targeted interventions to strengthen IPC practices.

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A systematic review and meta-analysis of the effectiveness of social prescribing in the management of long-term conditions.

Declan J. O’Sullivan1, Lindsay M. Bearne2, Janas M. Harrington1, Jefferson Rosa Cardoso3, Joseph G. McVeigh1 1. School of Clinical Therapies, UCC 2. Population Health Research Institute, St. Georges University, London 3. Laboratory of Biomechanics and Clinical Epidemiology, Universidade Estadual de Londrina Objective: To evaluate the effectiveness of social prescribing interventions in the management of longterm conditions in adults.

Data Sources: Eleven electronic databases were searched for randomized and quasi-randomized controlled trials.

Review Methods: Outcomes of interest were quality of life, physical activity, psychological well-being and disease-specific measures. Bias was assessed with the Cochrane Risk of Bias 2 tool. A narrative synthesis and meta-analysis were performed.

Results: Twelve studies (n=3566) were included in this review. Social prescribing interventions were heterogeneous, and the most common risks of bias were poor blinding and high attrition. Social prescribing interventions designed to target specific long-term conditions i.e. cancer and diabetes demonstrated significant improvements in quality of life (n=2 studies) and disease specific psychological outcomes respectively (n=3 studies). There was some evidence for improvement in physical activity (n=2 studies) but most changes were within group only (n=4 studies). Social prescribing interventions did not demonstrate any significant changes in general psychological wellbeing.

Conclusion: Targeted social prescribing interventions demonstrated significant improvements in quality of life and disease specific psychological well-being.

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Using wearable devices and AI to track the migraine cycle Caroline Peres da Silva1, Cian McCafferty2, Salvatore Tedesco1, Brendan O’Flynn1 1. Tyndall National Institute 2. Department of Anatomy and Neuroscience, School of Medicine, UCC Migraine is the most common neurological disorder worldwide, estimated to affect up to 1 billion people, while accounting for up to a quarter of workers’ annual sick-days per capita, with an annual expense of US $20 billion in the United States and €111 billion in the EU. Migraine is a chronic cyclical neurological disorder characterised by multiphase attacks of moderate to severe headache with associated central and autonomic nervous system sympathetic dysfunction and adrenergic hypersensitivity, typically manifesting as nausea, vomiting, and hypersensitivity to sensory stimuli during the migraine cycle.

Recent neuroimaging research shows that people who suffer from migraine have brain alterations compared to healthy controls. A portion of these alterations change dynamically over time according to the migraine phase (including prodromal and baseline phases), frequency of attacks, and disease duration.

These changes have been detected in structural and functional MRIs, CT scans, PET scans, and highdensity EEGs – all clinical diagnostic tools that are inaccessible as day-to-day treatments.

In this project, we aim to investigate if it is possible to track migraine attacks using consumer devices with sensors that monitor physiological signals, including wireless portable EEG, heart-rate variation, electrodermal activity, temperature, and photoplethysmography. A migraine dairy is used by patients as ground-truth to train a classification machine learning model. Incoming data from new subjects can then be automatically classified by the model, accurately predicting the migraine cycle.

The results of this project can be used to empower patients to better manage their condition and give early warnings of incoming attacks.

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Harnessing AI and Wearables for Personalized Mental Health Interventions Salvatore Tedesco1, Brendan O’Flynn1 1. Tyndall National Institute Leveraging AI and wearable technologies presents a transformative opportunity to advance innovative interventions for mental, behavioral, and neurodevelopmental disorders. AI can analyze large datasets from wearables to detect subtle changes in physiological and behavioral patterns, providing early warnings of symptom escalation in conditions such as severe depression, schizophrenia, and PTSD. These technologies enable real-time, continuous monitoring, offering more personalized and adaptive treatment strategies that extend beyond traditional clinical settings.

Wearables can unobtrusively track vital signs, activity levels, sleep patterns, and other relevant parameters, while AI algorithms process this data to identify trends and correlations that may not be apparent through conventional means. For instance, AI-driven analysis of heart rate variability and sleep disturbances could help in predicting relapses or exacerbations, allowing for timely intervention.

Furthermore, these tools can facilitate remote patient monitoring, ensuring that care is inclusive and accessible, particularly for those in underserved areas.

The integration of AI with wearable technologies also supports more informed decision-making for clinicians, enabling them to tailor interventions based on real-time data, thus improving the efficacy of treatments and reducing side effects. This approach aligns with the goals of creating lasting therapeutic benefits and bridging the gap between innovation and practical healthcare application, ultimately contributing to the reduction of disease burden and enhancing the quality of life for patients.

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The overexpression of human wild-type alpha-synuclein impairs GDNFmediated activation of Akt and ribosomal protein S6.

Jolie Z. Morisho1,3; Louise M. Collins1,2; Aideen M. Sullivan3,4,5; Gerard W. O’Keeffe1,4,5 1. Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.

2. Department of Physiology, University College Cork, Cork, Ireland.

3. Department of Pharmacology and Therapeutics, University College Cork, Cork, Ireland.

4. Parkinson’s Disease Research Centre (PDRC), University College Cork, Cork, Ireland.

5. APC Microbiome Ireland, University College Cork, Cork, Ireland.

A core pathological hallmark of Parkinson’s disease (PD) is intracellular proteinaceous inclusions of aggregated alpha-synuclein (aSyn). These aSyn inclusions disrupt the functionality of dopamine neurons in the nigrostriatal pathway, resulting in their progressive degeneration. The application of neurotrophic factors (NTFs) to protect these neurons is a promising therapeutic strategy. Glial cell linederived neurotrophic factor (GDNF) is the most well-known of these dopaminergic neurotrophic factors. Although preclinical studies provided evidence of GDNF-induced neuroprotection of dopamine neurons in neurotoxin models of PD, clinical trials of GDNF infusion in PD have failed to meet their primary endpoints. This may be due to disruption of the cellular response to GDNF in the presence of aSyn. In order investigate this, we examined the effects of aSyn on GDNF-mediated signalling.

Specifically, we examined the phosphorylation of Akt and S6, two key components of the PI3K/Akt/mTOR survival pathway, known to be necessary for the beneficial effects of GDNF. To investigate this, we used the SH-SY5Y cell line to examine if aSyn overexpression affected GDNFmediated pAkt and pS6 expression. Optical densitometry analysis revealed a ~15% increase in pAkt expression (p<0.05) and a ~148% increase in pS6 expression (p<0.05) in GFP-transfected cells treated with GDNF, compared to controls. In contrast however, there was no GDNF-induced increase in pAkt or pS6 in cells overexpressing aSyn. These data suggest that an increase in intracellular aSyn as seen in PD, may impair GDNF’s survival signalling potential via disruption of upstream (Akt) and downstream (pS6) components of the PI3K/Akt/mTOR signalling pathway.

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The voices are being heard: The UCC CTG PPI initiatives in cancer research.

Sasna S. Thomas1, Laia Raigal-Aran1, Jack Gleeson1,2, Katie E. Johnston1,2,4, Kate O’Connell1,2, Katarina Medved1,3, Josephine Hegarty5, Roisin M. Connolly1,2 1. Cancer Research @UCC, College of Medicine and Health, UCC, Cork, Ireland 2. CUH/UCC Cancer Centre, Cork University Hospital, Cork, Ireland.

3. School of Public Health, University College Cork, Cork, Ireland.

4. Clinical Nutrition and Oncology Research Group, School of Food and Nutritional Sciences, University College Cork, Ireland 5. Catherine McAuley School of Nursing and Midwifery, University College Cork, Cork, Ireland Background: The involvement of Public and Patient Involvement (PPI) in research is crucial as it ensures that research is more relevant, ethical, and impactful, ultimately leading to outcomes that better address the real needs and concerns of the community. The UCC Cancer Trials Group (CTG), an HRBfunded infrastructure established in January 2022, set a milestone to incorporate patient and public involvement (PPI) into its research initiatives.

Methods: The panel was developed with guidance from the PPI Ignite Network @ UCC, local and national charities with PPI experience and the National PPI Network. The objectives of the panel included were fostering a collaborative environment between researchers, patients, and the public; involving patients and the public in the design, implementation, and dissemination of cancer research; and ensuring that research outcomes align with patient needs and priorities. The two agreements were developed with UCC legal team assistance to support and safeguard interactions between the public and researchers, ensuring a structured and consistent approach. Additionally, three SOPs were adopted from the PPI Ignite Network @ UCC to guide PPI activities.

Results: In January 2023, the UCC CTG PPI panel was launched. The panel members were recruited through multiple channels: 1) social media posts, 2) an in-person informational event in November 2022, and 3) direct recruitment of former participants from our trials. Currently, the panel consists of 11 members, all of whom have lived experience with cancer.

The involvement process for the PPI panel members in our research begins with an email request from a designated UCC CTG officer. This officer provides the panel members with a brief description of the research request, after which the PPI members are encouraged to actively reach out to the researchers to offer their support. This non-invasive approach prioritizes the comfort and autonomy of each participant, allowing them to decide on their level of involvement according to their own preferences and comfort. Our researchers have received training information to an appropriate interaction with the PPI members to ensure appropriate approach.

Since the UCC CTG PPI panel establishment, the PPI involvement has included review of grant funding application (some being co-applicants), patient Information leaflet/informed consent (ex: LIAM Mc PIL, IMPROVE-TMZ), website content review and participation in committees.

Conclusion: The UCC CTG PPI initiatives have demonstrated significant value of involving patients voices through structured agreements, dedicated management by protecting and safeguarding the patients/publics voices. Future of the PPI activities will focus on expanding the panel, including more tailored PPI training for members and researchers and to continue ensuring patient-centred research.

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Wearable wireless system for electrochemical measurements using laserinduced graphene sensors.

Marco Sica1, Liudmila Khokhlova1, Hassan Hamidi1, Daniela Iacopino1, Brendan O’Flynn1 1. Tyndall National Institute Wearable devices have revolutionized healthcare and fitness by offering critical insights into individuals' health metrics and physical performance, thereby enabling more personalized and proactive approaches to well-being. Recent innovations in electrochemical front-end integrated circuits have significantly expanded the potential of wearable technology, allowing the integration of electrochemical testing capabilities into compact, power-efficient devices. The presented cutting-edge electrochemical wearable system is designed with a flexible transducer interface and an adaptable electronic configuration that can be tailored to detect various analytes (e.g., lactate, glucose) in sweat.

A key innovation of the proposed sweat sensor is the use of sustainable materials, such as laserinduced graphene, which not only reduce environmental impact. Additionally, the system features allows to implement multimodal sensing, enhancing its utility in comprehensive health monitoring by measuring related physiological parameters, such as skin temperature, heart rate or movement activity. Future efforts will focus on refining the system, including its integration into wearable clothing and benchmarking against established commercial solutions like the EmStat4 or PalmSens.

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A Cost-Effectiveness Analysis of a Community-Based Wheelchair Skills Training Intervention for Individuals with Neuro-physical Disabilities. Áine J. Gorman1, Dr Ann Kirby1, Dr Peter Cleary2, Dr Mari O'Connor1, Dr Aileen Murphy1 1. Department of Economics, Cork University Business School, UCC. 2. Department of Accounting & Finance, Cork University Business School, UCC. Background: The costs associated with neuro-physical disability (NPD) diagnoses are increasingly correlated with immobility. Community-based healthcare services, like the Crann Centre, enable access to comprehensive care for those in need. However, despite their invaluable service delivery, evidence regarding economic evaluations of community-based healthcare interventions, particularly for those living with NPDs, is limited.

Aims: This research conducts an economic evaluation of a community-based wheelchair skills training programme, i.e. the Crann Centre’s Skills on Wheels (SoW), for individuals with NPDs. Methods: The evaluation follows both national and international guidelines for the economic evaluation of health technologies. The intervention, SoW, is compared to usual care, i.e. no training.

In the baseline analysis, the perspective of the service provider is adopted, including costs directly attributed to programme provision, and benefits accruing to the individual. All resources employed in the delivery of both the intervention and usual care are identified, measured, and valued using microcosting techniques. Benefits are measured using results from two meta-analyses examining the effectiveness of wheelchair skills training programmes using the Wheelchair Skills Test (WST) and WST Questionnaire (WST-Q) total capacity scores. A cost-effectiveness analysis is conducted, where costs are related to WST/WST-Q capacity scores. The impact of parameter uncertainty is investigated through sensitivity analyses.

Results: Meta analysis results suggest that the intervention is more effective than usual care and preliminary cost analysis reveal additional costs are warranted to deliver the intervention.

Conclusion: This economic evaluation provides valuable information to support the continued viability and sustainability of community-based health services, and aid effective organisational service planning to achieve better physical health outcomes for individuals with NPDs.

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Cyclodextrins-Based Nanoparticles For Intestinal Delivery of RNA Francisca Soares1, Georgia Tsaridou1, Milo Malanga2, Kristóf Felegyi2, Miguel Ramôa1, Piotr Kowalski1, Caitriona M. O’Driscoll1 1. Department of Pharmaceutics, School of Pharmacy, University College Cork, Ireland 2. CarboHyde, Budapest, Hungary Crohn’s Disease manifests as chronic inflammation of the gastrointestinal (GI) tract. Current treatments for this condition, including steroids and immunomodulators, come with severe side effects and many patients become non-responders. The success of mRNA vaccines in the control of the Covid-19 pandemic illustrated the potential for RNA therapeutics. GENEGUT aims to develop an orally administered RNA-based therapy for Crohn’s disease. To ensure the delivery of intact RNA to the target tissue, an appropriate delivery vector capable of bypassing the barriers to oral administration is needed. This work explores the use of amphiphilic cyclodextrin (CD) nanoparticles to deliver siRNA to silence inflammatory pathways in intestinal cell models. A range of cationic amphiphilic β and γ cyclodextrins, with varying terminal amines and lipid chain lengths were synthesized, and nanoparticles (NPs) containing siRNA were formulated and characterized. Modification of cyclodextrin NPs with primary amines led to a significant (p&lt;0.05) increase of almost 4-fold (20% to 80%) in knockdown efficiency compared to modification with tertiary amines in an undifferentiated Caco-2 cell model. When cyclodextrin NPs were screened in a differentiated Caco-2 cell model, the knockdown efficiency decreased about 2-fold for all NPs. The formulations also maintained knockdown efficiency after incubation in Fasted Intestinal Biorelevant Media. Modification of CD:siRNA ratio influences uptake and knockdown efficiency.

Preliminary results indicate uptake of CD:mRNA formulations. These results indicate the ability of cyclodextrin NPs to deliver siRNA and mRNA to the intestine. Potential exists for further optimization of the formulations to enhance their efficacy.

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From Design to Dissemination: The Value of PPI in the LYSA Clinical Trial Katarina Medved1, Laia Raigal-Aran1, Katie E. Johnston1,2,4, Josephine Hegarty5, Roisin M. Connolly1,2, Sasna S. Thomas1, Kate O’Connell1,2 1. Cancer Research @UCC, College of Medicine and Health, UCC, Cork, Ireland 2. CUH/UCC Cancer Centre, Cork University Hospital, Cork, Ireland.

3. School of Public Health, University College Cork, Cork, Ireland.

4. Clinical Nutrition and Oncology Research Group, School of Food and Nutritional Sciences, University College Cork, Ireland 5. Catherine McAuley School of Nursing and Midwifery, University College Cork, Cork, Ireland Background: Patient and Public Involvement (PPI) is a critical element in ensuring that research is patient-centered and aligned with public needs. This study outlines the integration of PPI across various stages of LYSA (Linking You to Support and Advice) clinical trial, focusing on lessons learned and the impact on the research process.

Methods: The study followed INVOLVE guidelines, engaging PPI contributors from the early stages of trial design through to dissemination. PPI contributors participated in identifying research priorities, reviewing proposals, and designing study materials. Recruitment of PPI members was extensive, involving a network of healthcare professionals.

Results: PPI contributors collaborated with the Principal Investigator to refine the study proposal, making it more patient-focused. They co-designed study materials, improving their relevance and usability, including an electronic Patient Reported Outcome (ePRO) tool. PPI input resulted in meaningful amendments to study materials, enhancing their relevance and usability. The panel included six PPI contributors and 65 multidisciplinary stakeholders who engaged in regular virtual meetings throughout the study. Most PPI interactions (73%) occurring via email and a smaller proportion (19%) via Teams video calls. PPI discussions led to further research in the area of metastatic breast cancer. Contributors played a crucial role in disseminating findings through media, publications, and national awards.

Conclusion: The involvement of PPI contributors throughout the LYSA trial significantly enriched the study's design, implementation, and outcomes. Continuous engagement, trust-building, and flexibility are essential for successful PPI integration. These findings highlight the value of PPI in enhancing research quality and its potential to influence future studies.

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Role of the Gestational Maternal Gut-Microbiota in the Neurodevelopment of the Hypothalamus and the Amygdala Lorena Morales1,2, Hugo J. Blair1,2, Alexandre J. Cergneux1,2, Jennifer Morael1,2, Valentine Turpin1,2, Jennifer Shearer1,,2, John F. Cryan1,2, María R. Aburto1,2 1. Department of Anatomy and Neuroscience, School of Medicine, UCC 2. APC Microbiome Ireland, UCC The maternal gestational gut-microbiota has emerged as a potent modulator of neurodevelopment and increasing evidence links its alteration in the etiology of neurodevelopmental and neuropsychiatric conditions. The alar hypothalamus and the medial extended amygdala (EAme) are two key nodes of the social brain closely associated to these disorders. Notably, perinatal microbiota changes have been linked with morphological alterations in both brain regions. Moreover, microbiota-based interventions can modulate endogenous oxytocin levels in the hypothalamus. Hence, we hypothesized that the maternal microbiota influences the development of the alar hypothalamus and the EAme. To address this hypothesis, we used antibiotic treatment to deplete the maternal gestational gut microbiota in pregnant mouse females. Subsequently, we collected embryonic brains at E15.5 and examined radial glia (RG) led neurodevelopmental processes via immunofluorescence in two embryonic domains controlling the specification of both the EAme and alar hypothalamus: the telencephalon-optohypothalamic domain (TOH) and the supraopto-paraventricular hypothalamic domain core part (SPVco), respectively. Our findings reveal a decreased number of RG endfeet in the ventricular zone in the SPVco but not in the TOH in antibiotic treated mice compare to controls. In addition, both domains exhibited increased number of mantle zone radial glia in antibiotic treated mice. Collectively, these data suggest that maternal gestational microbiota modulates the production and dynamics of radial glia progenitors, potentially leading to morphological defects in both areas. Further research is warranted to elucidate its role in the differentiation and specification of the neuronal populations within these regions.

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Identifying unmet palliative care needs of nursing home residents: A scoping review Patrice Crowley1, Mohamad M. Saab1, Isabel Ronan2, Sabin Tabirca2, David Murphy2, Nicola Cornally1 1. Catherine McAuley School of Nursing and Midwifery, UCC 2. School of Computer Science and Information Technology, UCC Background: Many nursing home residents do not receive timely palliative care despite their need and eligibility. Screening tools as well as other methods and guidelines can facilitate early identification of nursing home residents unmet palliative care needs.

Aim: To map and summarise the evidence on identifying unmet palliative care needs of nursing home residents.

Methods: This scoping review was guided by the JBI Manual for Evidence Synthesis. Seven databases: CINAHL, MEDLINE, Embase, Web of Science, APA PsycINFO, APA PsycArticles and grey literature were systematically searched in February and March 2024.

Results: Forty six records were included in this review. Nineteen methods, five screening tools, four guidelines, and one framework were identified. There were 118 non disease specific indicators identified, with physical indicators being the most represented. Indicators were categorised into nine domains: physical, psychological, social, spiritual, healthcare, information, practical, autonomy, and personal issues.

Conclusion: This is the first scoping review to map and summarise the evidence on identifying unmet palliative care needs of nursing home residents. Future research should focus on defining the concept of “unmet palliative care needs” to facilitate its measurement in nursing home residents. The overall goal being to ensure timely and equitable access to palliative care for nursing home residents.

Key words: Care home; long term care; nursing home; palliative care; scoping review; screening; unmet needs.

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Prevalence and factors associated with depression and depressive symptoms: an integrative review Yue Wu1,2, Nicola Cornally1; Teresa Wills1, Aine O'Donovan1, Caroline Kilty1, Anqi Li2 1. School of Nursing and Midwifery, UCC 2. The First Affiliated Hospital of Nanjing Medical University China has the largest population of older persons, and depression is the most common mental health issue among this demographic. As societies continue to age, this trend is expected to increase globally, posing significant challenges to China’s health and social care systems. This integrative literature review aimed to map, summarize, and examine the empirical literature on the prevalence and factors associated with depression and depressive symptoms among Chinese older adults. Following Whittemore and Knafl's guidelines, databases searched included EMBASE, SCOPUS, CINAHL, Web of Science, PubMed, PsycINFO, SocINDEX, China National Knowledge Infrastructure Database, and Wanfang Database. Sixty-five studies (29 in English and 36 in Chinese) were included, reporting prevalence rates of depression or depressive symptoms ranging from 3.78% to 84.3%. Factors associated with depression were categorized using the biopsychosocial model: biological factors (physical health, disability, drug effects, gender, age, diet, physical activity), psychological factors (selfesteem, coping skills, trauma, emotions, beliefs, hobbies, lifestyle), and social factors (family relationships, peers, family circumstances, residential areas, social support, social structure).

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Building Social Capital - Essential and Desirable Characteristics for the Successful Large-Scale Implementation of a Targeted Selective Speech, Language and Communication Intervention Programme for Children Living in Social Disadvantage Pauline Frizelle1, Aoife O’Shea2, Omar Aftab1, Esther I. Atuhaire1 1. Department of Speech and Hearing Sciences, University College Cork, Cork, Ireland 2. Speech and Language Therapy Department, HSE, North Lee, Cork, Ireland Introduction: Targeted speech and language interventions such as Happy Talk (HT), aim to reduce social disparities and the lifelong consequences of language difficulties. To inform intervention implementation, this study aimed to examine factors which promote parental engagement and partnership between speech and language therapists (SLTs) and educators, to facilitate co-practice.

Methods: A qualitative methodology was used, in which 7 focus group interviews were conducted with SLTS (n=7), educators (n=17), and parents (n=12 ), who had previously delivered or taken part in HT. Participants were invited to discuss characteristics of HT that promoted stakeholder engagement and social capital. Data were analysed using reflexive thematic analysis. Data were reviewed by researchers independently, after which inductive coding was completed and findings were discussed to reach consensus on themes generated.

Results: Four themes were identified, namely, ‘Tailoring the Intervention to Stakeholders’, ‘Using Existing Relationships’, ‘Consideration of Stakeholder Perspectives’ and ‘Building Togetherness’. Parent and educator perspectives regarding SLT evolved as they engaged with HT over time and as positive outcomes emerged. These included more interactive relationships between parents and educators, and increased knowledge and confidence in their role in children’s language development. School atmosphere, relationships and flexibility on the part of SLTs were also highlighted as key factors for programme engagement.

Conclusion: Understanding the shared values between stakeholders and fostering meaningful relationships between them is central to promoting programme engagement and therefore effective delivery of HT in different contexts and communities.

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The Maternal Gut Microbiota Regulates Embryonic Cortical Development in Mice Hugo J. Blair1,2, Lorena Morales1,2, Alexandre J.C. Cergneux1,2, Jennifer Morael1,2, Valentine Turpin1,2, Jennifer Shearer1,2, John F. Cryan1,2, María R. Aburto1,2 1. Department of Anatomy and Neuroscience, School of Medicine, UCC. 2. APC Microbiome Ireland, Bioscience Institute, UCC. Embryonic neurodevelopment, which occurs in the sterile uterine environment, has recently been shown to be modulated by signals from the maternal gestational gut microbiota. We hypothesised this may occur through microbial signalling to radial glial cells, which generate cortical neurons, and function as a scaffold along which new-born neurons migrate. Therefore we aimed to study the effect of maternal gut microbiota depletion during pregnancy on radial glia-led neurodevelopment. Female mice were treated with an antibiotic cocktail prior to and throughout pregnancy to deplete their gut microbiota. Embryonic brains were collected at E15.5 and radial glia-led neurodevelopmental processes were examined via immunofluorescence. Embryonic CSF and maternal plasma were collected for metabolomic analysis via ultra-performance liquid chromatography-mass spectrometry.

Depletion of the gestational maternal gut microbiota affected embryonic radial glia-led neurodevelopment, as antibiotic group embryos showed alterations in radial glial and intermediate progenitor cells in the cortex. Alterations in progenitor cells were associated with changes in the structure of the cortical neuronal layers. The network of tight junctions expressed in radial glial apical endfeet at the ventricular interface was also seen to be affected, with no changes in the overall number of radial glial attachments to the ventricular wall. Finally, maternal antibiotic treatment altered the metabolomic profile of both the maternal plasma and embryonic CSF. In conclusion, we saw that maternal gut microbiota depletion during pregnancy alters the maternal plasma metabolome and some embryonic CSF metabolites, and leads to alterations in radial glial-led neurodevelopment.

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Caesarean Section and Risk of Psychiatric Disorders in Offspring during Adolescence and Adulthood: A Systematic Review and Meta-Analysis Moira Duffy1, Ali Khashan1 1. School of Public Health, University College Cork, Cork, County Cork, Ireland Aim: The aim of this systematic review and meta-analysis was to summarize available literature on the association between C-section birth and depression, anxiety, and psychosis in the offspring during adolescence and adulthood.

Methods: A systematic search of PubMed, PsycInfo, Web of Science, and Embase was conducted using a detailed and predefined search strategy. A meta-analysis was performed to determine overall pooled estimates, and the inverse generic variance method was utilized. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed for this review.

Results: 4,391 titles were reviewed for inclusion. Sixty articles were reviewed in full, of which 12 studies were selected. Three studies reported the impact of C-section on depression in the offspring during adolescence and adulthood: pooled OR (1.04 [0.99, 1.09]). Three studies evaluated anxiety: pooled OR (1.10 [1.03,1.08]). Nine studies evaluated psychosis, six were included in meta-analysis: pooled OR (1.10 [0.99, 1.22]). The number of studies in this research area is limited. Overall, there is very little evidence to support an association between C-section and the risk of depression, anxiety, or psychosis in the offspring.

Conclusion: This review examined an increasingly common operative procedure, C-section delivery.

Findings from the review can help inform best practice guidelines surrounding childbirth recommendations globally and contribute meaningfully to decision making by clinicians in the future.

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Collecting Information in Child Health Research Studies Moira Duffy1, Eibhlin Looney1, Dimity Dutch2, Brittany Johnson2, Laoise Kelly1, Lucy Porter3, Sarah Redsell3, Karen Matvienko-Sikar1 1. School of Public Health, University College Cork, Cork, County Cork, Ireland 2. Flinders University, Adelaide, South Australia, Australia 3. University of Nottingham, Nottingham, England, UK Introduction: Caregivers’ perspectives and preferences on Outcome Measurement Instruments (OMIs) used in child health trials may influence whether they and their children are likely to take part in trials that could impact child health research in the future.

Aim: The aim of this project is to examine what characteristics of OMIs are important in parents/caregivers’ decisions to engage with and participate in trials of interventions to prevent childhood illness and/or improve child health outcomes.

Methods: An online cross-sectional survey is being conducted. Survey recruitment began July 2024 and anticipated completion is October 2024 via social media, parenting websites, and online forums.

This survey examines what types of OMIs parents/caregivers would be most comfortable using to provide data in child health research. It also examines parents/caregivers’ preferences for where, how, when, and with whom data is collected in child health research. Data are being analysed using descriptive statistics.

Results & Conclusion: The data for this study is still being collected; findings from all participants will be presented at the conference. Preliminary findings from 257 participants indicate that the most influential factor for caregivers in child health research is the potential for risk to their child; the most preferred OMI is an online survey. Future child health studies need to consider the preferences of parents/caregivers as indicated in this study when designing and conducting research. This could improve participant engagement and the quantity and quality of data that underly study findings which could have implications for child health outcomes, research, and practice in the future.

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Association between Intrapartum Fetal Pulse Oximetry and Adverse Perinatal and Long-term Outcomes: a Systematic Review and Meta-analysis Jill M. Mitchell1,2, Siobhan Walsh, Laura J. O’Byrne1,2, Virginia Conrick3, Ray Burke4, Ali S. Khashan2,5, John R. Higgins1, Richard Greene1,6, Gillian M. Maher2,5,*, Fergus P McCarthy1,2,* 1. Department of Obstetrics and Gynecology, University College Cork, Cork, Ireland 2. INFANT Research Centre, Cork, Ireland.

3. UCC Library, University College Cork 4. Tyndall National Institute, Cork 5. School of Public Health, University College Cork, Cork, Ireland 6. National Perinatal Epidemiology Centre *These authors contributed equally and are joint senior authors.

Background: Fetal pulse oximetry may improve intrapartum fetal evaluation by providing non-invasive measurement of fetal oxygen saturation (FSp02).

Objective: To assess the association between abnormal intrapartum FSp02 and perinatal and longterm neonatal outcomes.

Searh Strategies: Studies published up to February 2024 were identified through PubMed, EMBASE, CINAHL, The Cochrane Library, Web of Science, ClinicalTrials.Gov and WHO ICTRP without temporal or language restrictions.

Selection criteria: Studies involving women in labour with a cephalic baby were included. Two interventions were reviewed: 1) Low FSp02 (<30%), and 2) the use of fetal pulse oximetry during labour.

Data Collection and Analysis: Independent reviewers screened studies, extracted data, and assessed quality using the Risk of Bias tool and Newcastle-Ottawa Scale. The approach evaluated evidence certainty. A random-effects meta-analysis followed PRISMA and MOOSE guidelines.

Main Results: Forty-seven studies with 13,071 mother-infant pairs were included. FSp02 <30% was associated with umbilical artery pH <7.15 (OR=7.86, 95% CI=[3.29-18.75], I2= 71%, p=0.0007), 5minute Apgar score <7 (OR=16.63, 95% CI=[5.64-49.01], I2=30%, p<0.00001) and NICU admission (OR= 5.89, 95% CI =[1.73-20.01], I2= 0%, p<0.005). FSpO2 monitoring combined with fetal heart rate monitoring was associated with lower odds of Caesarean section for non-reassuring fetal status (OR=0.59, 95% CI=[0.40-0.86], I2=71%, p=0.006) without impacting 5-minute Apgar scores <7 (OR=0.66, 95% CI=[0.37-1.17], I2=0%, p=0.16) or NICU admissions (OR=0.98, 95% CI=[0.82-1.18], I2=0%, p=0.84).

Conclusion: FSp02 monitoring combined with fetal heart rate monitoring may reduce unnecessary Caesarean sections for suspected fetal distress without affecting short-term neonatal outcomes. The association between FSp02 <30% and adverse perinatal outcomes supports its potential as a valuable adjunct in intrapartum monitoring.

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Factors influencing use and choice of Core Outcome Sets and Core Outcome Measurement Sets in trials of interventions to prevent childhood obesity.

Karen Matvienko-Sikar1, Dimity Dutch2, Moira Duffy1, Eibhlín Looney1, Victoria Brown3, John Browne1, Darren Dahly4, Declan Devane5, Janas Harrington1, Catherine Hayes6, Brittany Johnson2, Patricia M Kearney1, Jamie J Kirkham7, Patricia Leahy-Warren8, Andrew W Murphy9, Sarah Redsell10, Anna Lene Seidler11, Helen Skouteris12 1. School of Public Health, University College Cork, Ireland 2. Caring Futures Institute, College of Nursing and Health Sciences, Flinders University, Adelaide, South Australia, Australia.

3. School of Health & Social Development, Faculty of Health, Deakin University, Melbourne, Australia.

4. HRB Clinical Research Facility Cork; School of Public Health, University College Cork, Ireland.

5. HRB Trials Methodology Research Network, and Evidence Synthesis Ireland and Cochrane Ireland, School of Nursing and Midwifery, University of Galway, Ireland.

6. Public Health & Primary Care, School of Medicine, The University of Dublin Trinity College, Dublin, Ireland.

7. Centre for Biostatistics, The University of Manchester, Manchester, England, UK. 8. School of Nursing and Midwifery, University College Cork, Ireland.

9. HRB Primary Care Clinical Trials Network Ireland, University of Galway, Ireland.

10. School of Health Sciences, University of Nottingham, Nottingham, England, UK. 11. National Health and Medical Research Council Clinical Trials Centre, The University of Sydney, Sydney, New South Wales, Australia.

12. School of Public Health & Preventive Medicine, Monash University, Clayton, Victoria, Australia.

Aim: Childhood obesity is a public health challenge. Core Outcome Sets (COS) and Core Outcome Measurement Sets (COMS) can reduce heterogeneity and improve evidence syntheses for trials of childhood obesity prevention interventions. Two childhood obesity prevention COS have been developed, with COMS for these currently in development. This study aims to 1) examine trialists’ awareness and attitudes towards existing COS and factors influencing their use; 2) explore characteristics of COMS trialists currently use; and 3) understand how trialists choose COMS. Methods: An online, cross-sectional survey was conducted of trialists (n=51) involved in conducting and/or designing trials of interventions to prevent childhood obesity, in children 0-5years. Closedended questions included trialists characteristics, awareness of existing COS and factors influencing their use, characteristics of COMS, and how trialists choose COMS. Open-ended questions explored influences on trialists choice of outcomes and measurement instruments. Quantitative descriptive analysis, and qualitative content analysis are employed.

Results: Preliminary findings indicate 71% of respondents are familiar with COS; 55% are familiar with one or both childhood obesity prevention COS. Important factors for trialists when choosing COMS are: time, content validity, relevance for population, responsiveness, and reliability. Data analysis is ongoing, full results will be presented at conference.

Conclusions: Findings will inform approaches to maximising uptake of COS and COMS for childhood obesity prevention. The use of standardised approaches to what and how outcomes are measured will reduce research waste and outcome heterogeneity, and improve evidence syntheses to better determine intervention effects.

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Maternal Microbiome-Mediated Development

Effects

on

Offspring

Neurovascular

Alexandre J.C. Cergneux1,2, Valentine Turpin1,2, Lorena Morales1,2, Hugo J. Blair1,2, Jennifer Morael1,2, Jennifer Shearer1,2, John F. Cryan1,2, Maria R. Aburto1,2 1. APC Microbiome Institute 2. Department of Anatomy & Neuroscience, School of Medicine, University College Cork.

Recent investigations have emphasised the crucial role of maternal gut microbiota in shaping foetal brain development. Perinatal perturbations of the maternal gut microbiota have been associated with abnormal brain function and behaviour in offspring and broader alterations in neurodevelopmental trajectories. However, the mechanisms underlying this phenomenon are not yet fully understood. To address this gap, we employed two experimental models to explore the influence of perinatal maternal gut microbiota on brain angiogenesis and blood-brain barrier (BBB) development.

In our first experimental approach, we administered a wide-spectrum antibiotic cocktail to disrupt the maternal gut microbiota during pregnancy and examined its effects on foetal development. On embryonic day 15.5, we observed that the depletion of the maternal gut microbiota led to reduced vessel tortuosity in female offspring, while males exhibited increased pericyte coverage and vessel diameter.

We also used a caesarean section (C-section) mouse model to disrupt the vertical transmission of gut microbiota at birth, previously associated with an increased risk of disease and altered neurodevelopmental trajectories. By performing tracer injections, we observed that postnatal mice born by C-section presented increased permeability to the tracer in the brain parenchyma, suggesting disrupted blood-brain barrier permeability. This also coincided with the dysregulation of the tight junction proteins at the mRNA level. Notably, the overall ZO-1 coverage at the tight junctions remained unaffected.

Our research, while still in need of further investigation, has uncovered novel insights into the role of the maternal gut microbiota in promoting healthy brain vascularisation and BBB function during foetal and early postnatal life stages. These findings shed new light on the intricate interplay between maternal gut microbiota, brain angiogenesis, and BBB development during perinatal life and pave the way for targeted interventions that can enhance early-life neurovascular outcomes.

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Inhaler Usage and Environmental Impact. An Irish Perspective on knowledge, attitudes and environmentally friendlier prescription practices.

Anthony J. Goodings1, Tom Farrell2, Casandra Carey1, Sten Kajitani1, Rayan Ben Letaifa1, Tamara Vagg2, Kevin Deasy2, Hisham Ibrahim2, Desmond Murphy2, Barry Plant2 1. School of Medicine, UCC 2. Department of Respiratory Medicine, CUH Background: Pressurised Metered Dose Inhalers (pMDIs) use hydrofluorocarbons (HFCs), with a significant global warming potential. Alternative options exist with lower environmental impact, notably Dry Powder Inhalers (DPIs).

Methods: Post a review of relevant literature, we designed an inhaler environmental impact survey for healthcare professionals involved in the prescription/recommendation of inhalers at Cork University Hospital. Following ethical approval this survey is ongoing electronically (Qualtric software).

Results: Preliminary results (n=44: NCHDs 69%, Respiratory-nurse specialists 9%, RespiratoryPhysiotherapists 18%%, Pharmacists 4%) demonstrate that 48% prescribe/recommend pMDIs most frequently. 31% reported being aware of the environmental impact of inhaler choice, with 5% regularly discussing this with patients. 18% felt that environmental impact of medical products was adequately covered in their training to date.

With additional training 99% would be more likely to prescribe environmentally friendlier options.

Barriers to change identified include effectiveness (21%), compliance (25%) and local/national guidelines (18%). After reading a vignette on different inhaler environmental impact, 95% reported this would influence their future decisions. 88% believe their patients would be open to using environmentally friendlier options also.

Conclusion: This study demonstrates: 1) the lack of knowledge regarding the environmental impact of inhalers and 2) the willingness to change approach with appropriate education.

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General Practitioners’ and women’s experiences of perimenopause consultations: a qualitative evidence synthesis Laura-Jane McCarthy1, Aoife O’Mahony1, Aisling Jennings2, Sheena McHugh1 1. School of Public Health, University College Cork 2. Department of General Practice, University College Cork Background: Perimenopause precedes menopause and can cause a myriad of symptoms for women.

General practitioners (GPs) are often the first contact for perimenopausal women with symptoms.

However, some women report feeling dissatisfied with the consultations they have with their GPs for perimenopausal symptoms. Moreover, GPs can find these consultations difficult due to diagnostic challenges. To date, no evidence synthesis has examined how women experience perimenopause consultations, nor how GPs experience providing care to these women.

Objective: To systematically search, collate, and appraise the qualitative literature to understand how GPs and women experience perimenopause consultations and examine how treatment decisions are made during consultations.

Methods: A meta-ethnography as described by Noblit and Hare (1988) will be conducted following the guidelines of Sattar et al (2021). Seven databases will be systematically searched. To be included, qualitative studies must report on the experiences of GPs treating perimenopausal women and/or perimenopausal women seeking care. Quality assessment will be conducted using CASP (Critical Appraisal Skills Programme) tools. A GRADE-CERqual (Confidence in the Evidence from Reviews of Qualitative Research) will be conducted to assess the confidence of the findings.

Conclusion: Findings will shed new light on how GPs and women experience and perceive perimenopause consultations. Examining dual perspectives is key to ascertaining what works well during consultations and areas that can be improved upon. Findings may contribute to the future development of interventions to improve care for women during this time.

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THE-DIET: Facilitators' experiences of delivering a tailored health education resource to people with mild/moderate intellectual disability.

Dr. Anne-Marie Martin1, Ms. Anna Broderick2, Dr. Maria Caples1, Dr. Caroline Dalton-O’Connor1, Ms. Caroline Egan1, Dr. João Costa3, Mr. Seffie O’Donnell1, Ms. Lucia O’Neill2, Ms. Sandra Twomey2, Mr. Joe McCarthy2, Ms. Sile Divane2 1. School of Nursing and Midwifery, University College Cork 2. COPE Foundation 3. School of Education, University College Cork People with intellectual disability and support staff have highlighted that the lack of age-appropriate, accessible health information impedes people with intellectual disabilities from gaining the knowledge they need to make lifestyle decisions. Using a collaborative PPI approach with people with intellectual disability we co-designed a resource intertwining educational and personal development elements to address this gap. This IRC-funded pilot study explored the usability/feasibility of one component of this resource from the facilitators’ perspective. The objectives were to: • Explore facilitators' experiences of delivering the resource to people with mild/moderate intellectual disability.

• Identify facilitators' experiences regarding the resource usability • Identify modifications/supports required to support national rollout of the resource Eleven disability workers were recruited from the community hubs of a large intellectual disability service provider. They participated in pre and post focus group interviews, completed Laugwitz et al (2008) User Experience Questionnaire (UEQ) (adapted) and a collective journal of module delivery.

Qualitative data were analysed thematically while descriptive statistics were used to analyse the quantitative data.

A highly favourable user experience was identified from the high UEQ mean scores as were areas for enhancement. Qualitative data analysis (focus groups and facilitator journals) found the resource’s visual and tactile learning aids, and interactive, practical activities successfully engaged learners.

Resources were generally accessible and utilised well in each session.

Development of age appropriate, accessible resources is necessary for inclusive health promotion. This project demonstrates the power of PPI collaborators, practice and research working together to create inclusive health resources.

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Barriers and Enablers to Attendance at Structured Diabetes Education Programmes: A Systematic Review Chelsea Nwankwo1 1. School of Public Health, UCC Background: Structured diabetes education (SDE) programmes are important for effective diabetes self-management, yet attendance remains low among adults with Type 1 (T1D) and Type 2 diabetes (T2D). Factors such as logistical challenges, psychological barriers, and social influences have been identified as contributing to poor attendance. Understanding these factors is crucial for developing strategies to improve participation.

Aim: To identify and synthesise barriers and enablers influencing attendance at SDE programmes with T1D and Type 2 diabetes.

Methods: Studies were selected based on the SPIDER framework. Inclusion criteria focused on qualitative studies among adults aged 18 and older with T1D or T2D, exploring barriers and enablers to SDE attendance, and peer-reviewed articles in English from January 2014 to May 2024. Information sources included PubMed, CINAHL, and PsycINFO. Results were synthesised using the Theoretical Domains Framework (TDF) to identify and categorise factors influencing behaviour.

Results: Nine studies were included. Barriers were categorised using the TDF, including Knowledge (lack of awareness), Beliefs about Capabilities(confidence in self-management), Environmental Context and Resources (logistical challenges), and Emotion (stigma, denial). Enablers included Social Influences (healthcare providers’ recommendations), Environmental Context and Resources (proximity of SDE), and Beliefs about Consequences (awareness of risks).

Discussion: While SDE offers benefits, psychological, logistical, and emotional barriers affect attendance. Personalised communication from healthcare providers can help address these barriers.

Implications: These findings emphasise the need for more accessible, patient-centred diabetes education interventions, incorporating flexible scheduling to improve participation rates.

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Cadaveric Case Study of Vertebral Artery Coiling at the C3 Level: Anatomical Variability, Morphometric analysis and Clinical Implications Ashley Benge1, Mutahira Lone1, Andreea Factor1 1. Department of Anatomy and Neuroscience, School of Medicine, UCC Anatomical variations and anomalies in the origins and pathways of the vertebral arteries have significant implications for patients' clinical diagnosis and management.

Vertebral artery loop coiling is a rare anatomical variation1. The usually involved levels are C4–C5 and C5–C6, with the left vertebral artery most frequently affected2.

This cadaveric case study examines a rare bilateral vertebral artery loop coiling at the C3 level, exploring its anatomical characteristics and potential clinical significance.

Dissection of a 70-year-old female exposed a rare bilateral loop coiling of the vertebral arteries at the level of C3. Morphometric measurements were taken, including the external diameter of the arteries, the extent and nature of the coiling, and the length of the arterial segments. The left and right vertebral arteries were compared in size, tortuosity, and associated anatomical anomalies.

The rarity of this variation might be due to the anatomical characteristics of this region, which usually have less degree of vascular tortuosity.

Although rare, this variation can have significant clinical implications, especially in older individuals with age-related vascular degeneration and compromised blood flow.

Understanding vertebral artery variations, especially in atypical locations like C3, is essential for clinical diagnosis and planning interventional or surgical procedures.

1. Wood L, Czyz M, Forster S, Boszczyk BM. The diagnosis and management of a vertebral artery loop causing cervical radiculopathy. (2017) European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. doi:10.1007/s00586-017-5123-6 2. Semonche, A., Rinaldo, L., Lee, Y., Dubnicoff, T., Matles, H., Chou, D., Abla, A., & Chang, E. F. (2024).

Microvascular decompression of a vertebral artery loop causing cervical radiculopathy: illustrative case. Journal of Neurosurgery: Case Lessons, 7(9), CASE23254. https://doi.org/10.3171/CASE23254

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Engineering circular RNAs for selective protein expression in dysfunctional endothelial cells for the treatment of sepsis.

Nerea Hernández Egido1,2, Faiza Khalid1, Fatma Betul Dincaslan1,2, Meaghan Richardson1,2, Lianne M. Mulder1, Caitriona O'Driscoll1, Malgorzata Krajewska3, Piotr S. Kowalski1,2 1. School of Pharmacy, UCC 2. APC Microbiome Ireland, UCC 3. School of Biochemistry and Cell Biology, UCC The success of the messenger RNA-based vaccines against COVID-19 proved the clinical potential of RNA technology for protein production in vivo. Circular RNA is a new class of single-stranded RNA with a closed-loop structure that improves its stability due to the lack of free ends necessary for degradation by exonucleases. In contrast to messenger RNA, circular RNA is translated via Internal Ribosome Entry Site (IRES)-mediated cap-independent translation that often relies on the assistance of factors known as Internal Ribosome Entry Site Trans-Acting Factors which may vary in their expression depending on the cell type and cell state. IRES engineering could provide an avenue for tissue-specific expression by making circular RNA the preferred RNA for the ribosome in a cell under stress conditions in highmedical-need diseases such as sepsis. Here, we investigated a library of IRES sequences for their ability to drive robust and specific circular RNA translation under inflammatory conditions in endothelial and immune cells. IRES sequences were selected utilising relevant databases and the current literature and designed into the circular RNA context. Circular RNAs containing the 42 IRES candidates were synthesised, purified and assessed in vitro. Circular RNA designs containing Gaussia luciferase reporter gene were delivered into cell lines representing different cell phenotypes, including human endothelial cells (HUVEC, HMVEC), to study robust protein expression under cellular stress conditions. In vitro data was correlated with an in-silico computational analysis of the IRES to predict potential ITAFs binding the circular RNA.

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Developing Human Milk Oligosaccharides as Novel Polysaccharides for Microbiota-Triggered Release from Film-Coated Pellets Omar Sabra1, Joseph O'Shea1, Brendan Griffin1 1. School of Pharmacy, UCC Background and Aim: Recent advancements have highlighted the role of polysaccharides in maintaining gut health and facilitating site-specific drug delivery to the colon. The high colonic microbial density and diversity release enzymes metabolising polysaccharides, forming the basis for innovative colonic drug delivery strategies (CDDS). Human milk oligosaccharides (HMOs) promote beneficial bacterial expression in the colon; however, their bacterial metabolism from coating remains unexplored. This study aims to develop a film coating containing HMO (2'-Fucosyllactose; 2’FL), providing a promising CDDS. Methods: Theophylline-loaded pellets were prepared by extrusion/spheronisation and coated with Eudragit S100: 2’FL via fluid bed drying. Theophylline release was assessed through in-vitro dissolution studies over three hours in 500 ml phosphate buffer (pH 6.8) alone or supplemented with either βgalactosidase (25U/ml) or Bifidobacterium bifidum. Drug release was assayed via HPLC. Electron microscopy provided insights into the 2’FL-coated pellet surface.

Results: Film coatings incorporating up to 30% HMOs were successfully formulated, resulting in an 82.6% release of theophylline within one hour. Adjusting the composition of hydrophilic oligosaccharides and the coating level significantly delayed drug release, achieving a 43.3% release within three hours. The inclusion of β-galactosidase increased the release to 75.4%, while the presence of bacterial strain enhanced the release to 86.8%.

Conclusion: HMOs can effectively facilitate microbiota-triggered drug release, offering a promising strategy for targeted colonic drug delivery. This study's promising results support the potential for exploring the HMOs' effect on cultivating specific microbiota responsible for their digestion, thereby enabling site-specific drug release in the colon.

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Long term clinical outcomes in sustained dose reduction strategies for elexacaftor/tezacaftor/ivacaftor (ETI) – indications and outcomes: a case series Noreen Tangney1, Tamara Vagg1, K. Deasy1,2 , Mairead McCarthy1, James Dorgan1 , Claire Fleming1, Ciara Howlett1, Karen Cronin1, Edel O'Riordan1, Janice Mansfield1, Sara Twohig1, Hisham Ibrahim1,2, Barry James Plant1,2 1. Cork Centre for Cystic Fibrosis (3CF), Cork University Hospital, Cork (Ireland) 2. HRB Clinical Research Facility Cork, University College Cork, Cork (Ireland) Objectives: Real world data suggests that dose reduction strategies for ETI may be effective inthe short term in patients unable to tolerate full dose. We aim to review indications for dose reduction and long term clinical outcomes in a group of our patients maintained on a dose reduction strategy for a minimum of 12 months.

Methods: We identified six patients treated with both full and reduced dose ETI for at least 12 months respectively. A review of indications for dose reduction, 12 month average of clinical parameters (percentage predicted forced expiratory volume in one second (ppFEV1), sweat chloride (mmol/L), body mass index (BMI) (kg/m2), exacerbation frequency), and changes in low dose thoracic CT imaging reports while on each dose were recorded.

Results: Indications for dose reduction included anxiety, brain fog, psychosis and hyperactivity. Mean baseline ppFEV1 improved from 75 to 78 on full dose and remained relatively unchanged at 76 on reduced dose. Mean sweat chloride dropped from a baseline of 94.8 to 49.3 on full dose and 48.3 on reduced dose. Mean BMI increased from 23.2 at baseline to 24 at both full dose and reduced dose.

Mean exacerbation frequency at baseline was 0.4, 0 on full dose and 0.2 on reduced dose. CT findings were officially reported as stable for all patients on reduced dose when compared to full dose. Of note the neurocognitive indications for dose reduction resolved.

Conclusion: This case series supports clinical effectiveness of sustained ETI dose reduction in patients unable to tolerate full dose.

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Translational Chemistry and Microtechnologies for Biomedicine: Advancing the Alzheimer Disease Diagnostics through Molecular Pendulum Vuslat B. Juska1,2, Raquel Maria De Campos3, Alan O’Riordan2, William Klein3, Shana Kelley1,4,5,6,7,8 1. Department of Chemistry, Weinberg College of Arts & Sciences, Northwestern University, Evanston, IL, USA 2. Tyndall National Institute, University College Cork, T12R5CP, Ireland 3. Department of Neurobiology, Northwestern University, Evanston, IL, 60208, USA 4. Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, USA 5. International Institute for Nanotechnology, Northwestern University, Evanston, IL, USA 6. Department of Biochemistry, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA 7. Simpson Querrey Institute, Northwestern University, Chicago, IL, USA 8. Chan Zuckerberg Biohub Chicago, Chicago, IL, USA Alzheimer's disease (AD) is the most common and impactful neurodegenerative disorder, accounting for 60-70% of dementia cases. In 2016, it was reported that 26.6 million people worldwide had AD, and this number is projected to rise to 106.8 million by 2050, including 16.51 million in Europe, representing an 87% increase. The economic burden is expected to reach US$2.8 trillion by 2030. To tackle the challenges of AD diagnosis, we developed a rapid, sensitive, high-performance monitoring tool for amyloid-beta oligomers. This system combines the scFv antibody fragment with a molecular pendulum, integrated through a silicon device at the nanoscale interface. Such biointerface enables conformation-specific binding of amyloid-beta oligomers, providing an electrical output within milliseconds. Our platform can detect the target oligomers at concentrations as low as 10 femtomolar.

Besides we expand the sensor fingerprints through neuroinflammation, which plays a key role in disease progression over time. Our reagent-free inverted pendulum approach is a promising candidate for becoming the gold standard in near-future personalized healthcare, offering high-performance screening and sensing capabilities. This innovative platform is poised to replace costly methods (e.g.

ELISA and bioassays), providing a more efficient, affordable, and accessible solution for diagnostics.

This talk will summarize the development of the bioelectronic device and its broad applicability through neurodegeneration and inflammation.

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Advancing biobanking and sample utilization in blood cancer research: A report from the Blood Cancer Network Ireland (BCNI) Biobank, Cork.

C. Nolan1, E. Szegezdi2, D. O’Shea3, E. Molloy3, V. Mykytiv3, O. Gilligan3, M.R. Cahill1,3 1. Cancer Research @UCC, College of Medicine and Health, University College Cork, Ireland 2. Apoptosis Research Centre, School of Biological and Chemical Sciences, University of Galway, Ireland 3. Haematology Department, Cork University Hospital; Cork, Ireland The Blood Cancer Network Ireland (BCNI) Biobank, part of a collaborative network founded in 2016, stores high-quality patient samples for research. Samples from hospitals in the BCNI network (UHG, CUH, UHL, St. James’s, Beaumont, The Mater, and Waterford) are processed and stored either locally or centrally in Galway under Blood Cancer Biobank Ireland.

The BCNI Biobank database holds 824 participant records, with contributions from CUH - 326, University Hospital Limerick-205, Beaumont Hospital-115, UHG-93, St James’-52, Mater Hospital-18, University Hospital Waterford-9, Midlands Regional Hospital-4. In the past 12 months UCC has recruited 65 new patients.

In UCC, the biobank stores samples from 156 Chronic Lymphocytic Leukaemia (CLL), 92 Acute Myeloid Leukaemia (AML), and 54 Multiple Myeloma patients, making it an invaluable resource for studies requiring extensive samples. In 2024, 835 ‘specimens’ have been collected across all sites, with 447 stored at the Cork branch.

A key development at BCNI involves expanding biobanking to include lymphoma and circulating cellfree DNA (cfDNA) sampling at UCC, offering insights into non-invasive monitoring of lymphoma. To date, 15 patients have been recruited for this study, with 31 serial samples collected before, during, and after treatment.

The biobank has focused on aligning with ISO 20387:2018 standards over the past 24 months, conducting 5 internal audits to improve quality standards. As we expand biobanking to include lymphoma, it is vital to recognize the untapped potential of our existing biobank. Promoting and fostering sample utilisation through collaborative research will significantly advance blood cancer research and improve patient care.

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Retinoid specificity in mediating growth suppression in glioblastoma stem cells Patricia M. Flynn1, Collette K. Hand2, André Toulouse1 1. Department of Anatomy and Neuroscience, School of Medicine, University College Cork, Cork, Ireland 2. Department of Pathology, School of Medicine, University College Cork, Cork, Ireland Glioblastoma is the most common and aggressive cancer of the central nervous system, characterized by poor prognosis and limited treatment options, with 95% of patients succumbing within 24 months of diagnosis. Novel therapies are urgently needed. Retinoic acid, a vitamin A derivative, has shown potential in inhibiting cancer cell growth through its action on retinoic acid receptors (RARs). This study investigates the effects of retinoic acid on glioblastoma stem cells (GSCs), focusing on the differential expression of RAR isoforms and the use of isoform-specific retinoids.

We treated eight GSC lines with various retinoids, including all-trans retinoic acid (ATRA) as a panagonist, and isoform-specific retinoids targeting RARα, RARβ, and RARγ, for six days to assess cell viability using the WST-8 assay. Additionally, we performed quantitative PCR (qPCR) to analyse RAR isoform expression pre- and post-treatment. Our findings indicated that GSC lines exhibited variable RAR expression patterns, suggesting that the efficacy of retinoic acid may depend on the specific RAR isoforms present.

Further experiments revealed which isoform-specific retinoids effectively suppressed glioblastoma cell growth. By understanding the expression levels of RAR isoforms and their response to ATRA and other retinoids, we identified optimal retinoid combinations for therapeutic efficacy. This study underscores the potential of retinoic acid in glioblastoma treatment by selectively targeting RAR isoforms, paving the way for more effective therapies and improved patient outcomes in this challenging malignancy.

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Examining the therapeutic potential of AAV-GDF5 and AAV-GDNF in an αsynuclein rat model of Parkinson’s disease Fionnuala E Wilson1,2, Martina Mazzocchi2, Louise M Collins2,3,4, Gerard W O’Keeffe2,3,4*, Aideen M Sullivan1,4,5* 1. Department of Pharmacology & Therapeutics, School of Medicine, University College, Cork, Ireland 2. Department of Anatomy & Neuroscience, University College Cork, Ireland 3. Department of Physiology, School of Medicine, University College Cork, Ireland.

4. Parkinson’s Disease Research Cluster (PDRC), University College Cork, Ireland 5. APC Microbiome Ireland, University College Cork, Ireland * Joint senior authors Parkinson’s disease (PD) pathophysiology involves midbrain dopaminergic neuron degeneration, accompanied by intraneuronal accumulation of α-synuclein (αSyn). Adeno-associated virus (AAV)mediated delivery of neurotrophic factors (NTFs), including GDNF, has shown potential in clinical trial to be used as disease-modifying therapy for PD. The NTF GDF5 has been shown to exert protective effects on the nigrostriatal pathway following intranigral delivery in an αSyn rat model of PD. Here, we examined whether delivery of GDF5 or GDNF to the striatum, a more clinically accessible brain site, exerted neuroprotective effects in the αSyn rat PD model. Following behavioural testing at baseline, female Sprague-Dawley rats (n=24) received unilateral intranigral injection of AAV- αSyn and instrastriatal injection of either AAV-Null, AAV-GDF5 or AAV-GDNF. Behavioural testing was performed at 12-, 16- and 20-weeks post-surgery. After 24 weeks, brains were stained for tyrosine hydroxylase (TH) and inflammatory markers. Strong ipsilateral GDNF overexpression was observed in the nigra in the AAV-GDNF group, showing that GDNF had been retrogradely transported to the nigra from the striatal injection site. However, ipsilateral nigral overexpression of GDF5 was not observed. There were no significant differences between numbers of dopaminergic neurons in the ipsilateral nigra, or of striatal dopaminergic terminals, between the groups. No significant differences were observed between groups in the cylinder or the grid-walking motor tests. This shows that intrastriatal delivery of AAV-GDNF or AAV-GDF5 did not provide significant neuroprotection of nigrostriatal dopaminergic neurons against αSyn-induced degeneration. This provides important information regarding the optimal injection site for future clinical trials in PD patients.

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Expanded Vδ1 γδ T cells from healthy donor PBMCs display a cytotoxic phenotype with cytotoxicity elicited against colorectal cancer cells.

Amy Walsh1,2, Anthonia Ekperuoh1,2, Rosemary O’Connor3, Henry Paul Redmond1,2, Cathriona Foley1,2 1. Department of Surgery, School of Medicine, College of Medicine and Health, University College Cork, Cork, Ireland 2. Department of Surgery, Cork University Hospital, Cork, Ireland 3. School of Biochemistry and Cell Biology, Biosciences Institute, University College Cork, Cork, Ireland Purpose: Mismatch repair-deficient (MMR-d) colorectal cancer (CRC) tumours use the loss of HLA-I antigen presentation as an escape mechanism from αβ T-cell-mediated immunity. However, HLA-Iunrestricted, cytotoxic γδ T-cells have highlighted their potential use in broader cancer immunotherapy. This study aimed to expand Vδ1 T-cells from PBMCs and assess cytotoxic killing of CRC cells.

Methods: γδ T-cells were expanded from PBMCs of five healthy donors. αβ T-cell-depleted, CD3+ cells were cultured with IL-15, anti-CD2, and anti-CD3, for 18±1 days. γδ T-cells isolated from seven additional donors were cultured with or without IL-18 for 18±1 days. Expanded products were phenotyped by flow cytometry, excluding those with >1% αβ T-cells from further analysis. Cytotoxicity was assessed by tumour-killing assays using expanded T-cells and CRC cell lines (HT-29 n=5, SW480 and SW620 n=3) at Effector:Target (E:T) ratios, 0:1, 5:1, 10:1, and 20:1.

Results: γδ T-cells expanded from 1.4x10^6 to 3.4x10^6 by day 18±1 (*p=0.0105). CD3+Vδ1+ T-cells expanded without IL-18, increased from 9.95% to 51.3%, and 38.8% with IL-18. Vδ2 T-cells decreased from 21.3% to 19.5% without IL-18 but increased to 37.5% with IL-18. On average, >90% of Vδ1 T-cells expressed NKG2D. Expanded γδ T-cells showed cytotoxicity against CRC cell lines, significantly killing HT-29 cells at E:T ratios 10:1 (16.2%,*p=0.128), and 20:1 (25.7%,**p=0.0066), compared to the control (0:1, 0%).

Conclusion: γδ T-cell products enriched with CD3+Vδ1+ T-cells exhibiting cytotoxicity against CRC cells, supports ongoing research into Vδ1 T-cells as a potential CRC cellular therapy.

Funding: 5ForTheFight/Breakthrough Cancer Research (C&CRA 2023 074).

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Lactobacillus rhamnosus Soluble Mediators Improve Cell Viability and Display Anti-inflammatory Properties on LPS-Induced Inflammation of VK2 Cells Mariarosaria Cuozzo1, Harriet Schellekens1, Jens Walter2,3, Luiza Wasiewska1, Friederike Uhlig1, Siobhian O'Mahony4 1. APC Microbiome Ireland, University College Cork, Ireland 2. School of Microbiology, University College Cork, Ireland 3. Department of Medicine, School of Medicine, University College Cork, Ireland 4. Department of Anatomy and Neuroscience, University College Cork, Ireland The balance of vaginal microbiota plays a pivotal role in maintaining vaginal health and overall wellbeing. This role can largely be attributed to Lactobacillus species which provide defense against invading pathogens through their production of antimicrobial and anti-inflammatory products.

Intriguingly, factors such as menopause, stress, hormonal changes, and pathologies like endometriosis are associated with vaginal microbiota changes, leading to increased susceptibility to infections and inflammation. Understanding and maintaining the balance of vaginal microbiota is essential for preventing complications and promoting female wellness.

This study examined if Lactobacillus rhamnosus could act as a postbiotic in an in vitro model of vaginal inflammation. Cell-free supernatants (CFS) from L. rhamnosus were tested for 12 hours on a vaginal epithelial cell line (VK2/E6E7) pre-stimulated with LPS. The results showed an increase in cell viability and suppression of LPS-induced epithelial damage as indicated by a significant reduction in LDH release. Additionally, we found that L. rhamnosus CFS exerted a protective role in NFkB signaling-mediated inflammation when compared to the culture media without bacterial supernatants. These results were also accompanied by significant antiinflammatory effects, in particular on IL-6 production.

While probiotics remain a well-established approach, the study suggests that probiotic supernatants may offer enhanced physiological effects. In particular, L. rhamnosus CFS may influence the response of vaginal epithelial cells to LPS-induced inflammation, indicating a potential role for postbiotics in enhancing women's vaginal health. Overall, the study suggests using vaginal bacterial metabolites in health products to support microbiome balance and manage conditions for women's overall wellbeing.

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Exploring the Impact of a Dietetic Intervention on Body Composition in Breast and Gynaecologic Cancer Survivors: Results from the Linking You to Support and Advice [LYSA] Randomised Control Trial Katie E. Johnston1,2,3, Kate O’Connell1,2, Laia Raigal-Aran1, Aoife M. Ryan3, Brendan Palmer4, Darren Dahly4, Josephine Hegarty5, Samantha J. Cushen3* and Roisin M. Connolly1,2* 1. Cancer Research @UCC, University College Cork, Cork, 2. UCC/CUH Cancer Centre, Cork University Hospital, 3. Clinical Nutrition and Oncology Research Group, School of Food and Nutritional Sciences, University College Cork, Cork 4. Clinical Research Facility Cork, School of Public Health, University College Cork, Cork, 5. Catherine McAuley School of Nursing, University College Cork, Cork, Ireland * Senior Authors Rationale: Altered body composition is linked to poor cancer-related outcomes and treatment toxicity in cancer survivors. Qualitative research highlights that cancer survivors are unlikely to receive optimal support to manage these alterations.

Methods: Females with early-stage breast or gynae (GYN) cancer <12 months post-primary curative therapy were randomised to an experimental or active comparator (AC) arm in the LYSA Trial. Although not powered for treatment effect, a secondary outcome investigated body composition. Assessments at baseline and 12 months included lean tissue mass and adipose tissue mass via bioelectrical impedance analysis; muscle strength via handgrip strength, waist circumference and body mass index.

The experimental arm completed ePROs bi-monthly, including body weight and weight gain concern (WGC), triggering a nurse and dietitian-led personalized symptom management pathway.

Results: 200 participants enrolled to the trial (mean age: 55yrs). N = 73 initiated 243 dietetic consultations. Body weight remained stable over time between experimental and AC arms (p=0.521).

Both arms showed increases in lean tissue mass over time (p=0.351). Decreases were noted in both waist circumference [-0.35 (-1.84 to 1.14)] p=0.643 and adipose tissue mass [-0.3 (-1.43 to 2.04)] p=0.73.

Conclusion: The use of ePROs to implement a dietetic and nurse-led survivorship intervention was feasible. The impact on changes in weight and lean tissue mass should be explored in future trials powered to detect a difference in these endpoints.

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Body Composition in Males Impacted by Metastatic Genitourinary Cancer: Results from the Pilot Component of the LIAM Mc Trial.

Katie E Johnston1,2,3, Stephanie Corkery1,2,4, Anita Cahill1,2,5, Laia Raigal-Aran1, Brendan Noonan6, Samantha J Cushen1,3 and Jack P Gleeson1,2 1. Cancer Research @UCC, College of Medicine and Health, University College Cork, Ireland 2. CUH/UCC Cancer Centre, Cork University Hospital, Cork 3. Clinical Nutrition and Oncology Research Group, School of Food and Nutritional Sciences, University College Cork, Ireland 4. Department of Physiotherapy, Cork University Hospital, Ireland 5. Department of Urology, Cork University Hospital, Ireland 6. Catherine McAuley School of Nursing and Midwifery, University College Cork, Ireland Introduction: The impact of body composition on long-term survival and cancer recurrence has been well documented in genitourinary cancers. While supervised exercise and nutrition interventions are effective in addressing muscle loss, their feasibility as part of a multidisciplinary intervention remains unclear.

Objective: To evaluate the effectiveness and feasibility of a 12-week multidisciplinary interventional programme, designed for metastatic genitourinary cancer survivors, on body composition.

Methods: The LIAM Mc Trial is a 12-week dietary and exercise intervention led by a dietitian, physiotherapist, and advanced nurse practitioner (ClinicalTrials.gov: NCT 0594699). The intervention involved five group dietetic sessions, bi-weekly exercise sessions, and signposting to supports. Body composition assessments included body mass index (BMI), lean tissue mass [LTM], fat mass [FM] (using bioelectrical impedance analysis), waist circumference (WC), and handgrip strength.

Results: Five participants (62.6 ± 7.7 years) were enrolled in the pilot study (completed September 2023), with 87% attendance at all supervised exercise sessions and 84% at all dietitian group education sessions. Across the supervised intervention, there was a reduction in WC (-0.2cm p=0.910), an increased LTM (+1.5kg p=0.298), an increased FM and BMI (+0.58kg p=0.910; +0.75kg/m2 p=0.080 respectively). Significant improvements were noted in handgrip strength (+4.88kg p=0.032).

Conclusion: Results support the feasibility of implementing a dedicated multidisciplinary programme led by AHPs to improve LTM & muscle strength in men with genitourinary cancer. The trial has progressed to the main interventional programme and relocated to a state-of-the-art rehabilitation facility based on pilot cohort feedback, with 25/72 participants recruited at submission.

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What and how we measure outcomes in health research matters: The example of childhood obesity prevention Karen Matvienko-Sikar1 1. School of Public Health, UCC Introduction: Heterogeneity in what and how health outcomes are measured in trials limits evidence synthesis, ability to determine intervention effectiveness, and increases research waste. Such heterogeneity in trials of childhood obesity prevention interventions likely contributes to inconsistencies in understanding what interventions work, or not. This research aims to standardise and improve measurement of infant feeding outcomes to prevent childhood obesity through development of a core outcome set (COS) and core outcome measurement set (COMS).

Methods: A COS was developed through a 3-step systematic process involving: 1) a systematic review to identify what outcomes are currently measured; 2) an international e-Delphi survey; 3) a stakeholder consensus meeting, including parents, healthcare professionals, policy makers, childcare providers, and researchers. COMS development also follows a systematic process, the first step of which involves identifying what outcome measurement instruments (OMIs) are currently used to measure the COS outcomes.

Results: The systematic review conducted during COS development identified 236 outcomes measured in 126 studies. The e-Delphi and consensus meeting resulted in a COS including 26 outcomes grouped in 9 outcome domains (e.g., 'food environment', 'dietary intake', and 'child weight'). The review of what OMIs are being used to measure the COS outcomes has identified 212 OMIs in 157 trials. Next steps of COMS development involving evaluating measurement properties are ongoing.

Conclusion: Use of the COS and COMS will enable more comprehensive examination and synthesis of the effects of infant-feeding interventions to prevent childhood obesity, with important implications for research, policy and practice.

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Luminal Lithocholic acid can modify colonic secretory function via basolateral secretion of interleukin-6.

Qiao Xiao1,2, Susan A. Joyce2,3, Dervla O'Malley1,2 1. Department of Physiology, College of Medicine and Health, University College Cork, Cork, Ireland.

2. APC Microbiome Ireland, University College Cork, Cork, Ireland.

3. School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland.

Background: Lithocholic acid (LCA) is a potent agonist of TGR5. Bile acid are altered in individuals with IBS. Study has highlighted LCA-mediated activation of interleukin-6 (IL-6) signalling molecules.. This study aimed to determine the mechanistic pathways that LCA modifies gut function in animal model and to investigate a possible role for IL-6.

Methods: Mass spectrometry was utilized to compare the bile acids in SD rats and WKY rats.

Fluorescent immunolabeling was employed to study the expression of TGR5 and IL-6 receptors. Ussing chambers and ELISA were used to assess the functional impact of LCA on transepithelial ionic movement and the capacity of LCA to stimulate secretion of IL-6.

Results: In WKY rats, total bile acids are reduced and LCA levels are decreased. TGR5 and IL-6 receptor were expressed mucosally and on submucosal neurons. Baseline secretion of IL-6 was elevated in WKY, but LCA increased the IL-6 secretion only in SD rats. Functionally, LCA can down-regulate carbacholinduced secretion, but this can be blocked using neutralizing IL-6R antibodies. LCA also reduces veratridine-induced secretion, Independent of IL-6.

Conclusions: Luminal LCA stimulates colonic secretion of IL-6 in healthy rats. However, IL-6 secretion is already elevated in WKY colonic tissue and is not further enhanced by LCA. Functionally, LCA suppressed neuronally-mediated colonic secretion. IL-6 was critical to cholinergically-mediated colonic secretion but not secretory currents induced by veratridine. The interaction between secondary bile acids and pro-inflammatory cytokines are important in colonic function, and this may be further modified in disorders of gut-brain interaction.

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Prospective Evaluation of the Breast Microbiome and Tumour Microenvironment-related Biomarkers of Response to Neoadjuvant Systemic Therapy in Triple Negative Breast Cancer Emilene S. Morais1, Maeve A. Hennessy2, Ciarán P. Devoy1, Grace Walsh1,2, Erin Crowley1,3, Emer Lynch2, Maria Twomey2,4, Corina Girleanu2,5, Darren Dahly5, Lorraine O’Driscoll6, Cathriona Foley7, Michael W. Bennett2,3, Deirdre O’Hanlon2,7, Munawar Abbas1,8, Asma Amamou8, Subrata Ghosh8, Mark Tangney*1,8, Roisin M. Connolly*1,2 1. Cancer Research @UCC, College of Medicine and Health, University College Cork, Ireland 2. CUH/UCC Cancer Centre, Cork, Ireland 3. Clinical Research Facility-UCC, University College Cork, Ireland 4. Department of Radiology, Cork University Hospital, Ireland 5. Department of Academic Pathology, Cork University Hospital, Ireland 6. Trinity St James Cancer Institute, Dublin, Ireland 7. Department of Surgery, School of Medicine, University College Cork, Ireland 8. APC Microbiome Ireland, University College Cork, Ireland *Co-Last Authors Background: Predictive biomarkers of response to chemotherapy and immune-checkpoint inhibitors are urgently needed to tailor treatment recommendations for patients with early-stage triple-negative breast cancer (eTNBC). Recent advancements have revealed that the breast hosts bacteria in both normal and malignant tissue, with our group identifying tumour-associated microbiota as promising biomarkers in breast cancer. We aim to examine the breast microbiome and tumour microenvironment in eTNBC treated with neoadjuvant chemo-immunotherapy, correlating these findings with clinical outcomes.

Trial Design: This study is enrolling patients with eTNBC eligible for neoadjuvant therapy followed by surgery. The primary objective is to assess changes in the breast microbiome composition pre- and post-therapy. Secondary objectives include correlating the microbiome with pathologic response, survival, tumour-infiltrating lymphocytes, and PDL-1. Tumour tissue samples will be collected at baseline and surgery, followed by microbiome analysis through metagenomic sequencing. Blood and stool samples will be collected and analysed at multiple timepoints for secondary endpoints.

Statistical Methods: Hierarchical clustering, Alpha and Beta Diversity analyses, principal component analysis, and Random Forest methods will be used for data classification and clustering. Thirty patients will be recruited over 18-24 months. CREC approval was obtained in March 2024 and the trial is activating in CUH in September 2024.

Conclusion: This trial will provide a deeper insight into the role of the breast microbiome as a predictive biomarker for response to neoadjuvant therapy in patients with eTNBC. Results will guide future studies on immunomodulatory treatments and potential therapeutic targeting of the breast microbiome.

Funding: Breast Cancer Research Foundation

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Safe Staffing: The Pilot Testing of the RUG-IV Instrument in Ireland.

Ms Rachel Linehan1, Dr Ashling Murphy1, Dr Vera McCarthy1 & Professor Jonathan Drennan2 1. School of Nursing and Midwifery, University College Cork.

2. School of Nursing, Midwifery and Health Systems, University College Dublin.

Introduction: The Resource Utilisation Group (RUG-IV) instrument is a classification system which allows resident acuity to be classified within the Long-Term Residential Care (LTRC) setting. It has typically been used in the US healthcare setting.

Aims and Objectives: The aim of this paper is to determine if resident acuity in LTRC settings in Ireland, as measured by the RUG-IV instrument, is comparable to international evidence.

Methods: Descriptive pilot study, conducted in eight LTRC settings with a wide geographical spread across rural and urban settings in Ireland. Four public, two private and two voluntary LTRC settings took part in the pilot study. Data was collected once a month over seven time points. The RUG-IV instrument was presented in an Excel based workbook which was shared with the LTRC settings for completion. The RUG-IV instrument comprises of 43 subcategories which are grouped into 6 categories: Extensive Services; Special Care High; Special Care Low; Clinically Complex; Behavioural Symptoms and Cognitive Performance and Reduced Physical Functioning.

Results: Across the eight LTRC settings, the greatest proportion of residents were categorised into Reduced Physical Functioning at 56%, followed by Behavioural Symptoms and Cognitive Performance (25%), Special Care Low (9%), Special Care High (6%), Clinically Complex (3%) and Extensive Services (1%).

Conclusion: The RUG-IV instrument presented evidence that is comparable to international trends with the majority of residents within the Reduced Physical Functioning category. The instrument provides a digital means of measuring resident dependency levels which can inform safe staffing levels within the LTRC setting.

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Investigation of the impacts of maternal prebiotic supplementation on anxiety and depression-like behaviours during postpartum and early life stress in female mice.

Amiee M. Cronin1,2, Yvonne M. Nolan1,2, Olivia F. O’Leary1,2 1. Department of Anatomy and Neuroscience, School of Medicine, University College Cork, Ireland.

2. APC Microbiome Ireland, University College Cork, Ireland.

Stress during childhood increases the risk of developing anxiety and depression. Biological sex is also a risk factor with women being uniquely vulnerable to postpartum depression and being two-times more likely to develop depression than men. This vulnerability emerges in adolescence, when sex differences in gut-microbiome composition appear. Despite this, few studies have investigated the contribution of the maternal gut-microbiome in female susceptibility to stress-related disorders and have focused predominantly on males. Therefore, we investigated whether stress (limited bedding and nesting model) applied during the postpartum period when the pups are still with their mother, impacts anxiety and depressive-like behaviours in mothers and their adolescent offspring in a sexspecific manner, and if this can be prevented by manipulation of gut microbiota via administration of the prebiotics fructo- and galacto-oligosaccharides (FOS+GOS).

Upon Confirmation of a pregnancy plug, C57BL\6 adult female mice received 7.5% FOS+GOS in their drinking water or normal water for the duration of the experiment. Dams and their litter underwent standard housing or limited bedding and nesting from postnatal day 4 to 11. Dams (postpartum day 23 +/-1) and offspring (postnatal day 27 +/-1) underwent a battery of behavioural tests assessing anxiety and depressive-like behaviours (n=8-10).

FOS+GOS reduced anxiety in stressed dams and stressed male and female adolescents in the marble burying test. Analysis of remaining behavioural tests is currently underway. These findings will contribute to improving strategies to protect maternal mental health and the development gut microbiota-mediated treatment strategies for stress-related psychiatric disorders.

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Shaping Healthy Eating: Priming healthy eating behaviour from early life to adulthood in mice using microbiota-targeted interventions Cristina Cuesta-Marti*1,2, Eduardo Ponce-España*1,3,4, Friederike Uhlig*1,2, Thomaz Bastiaanssen2, Gabriel Tofani1,2, Benjamin Valderrama1,2, Cristina Rosell-Cardona2, Iris Stoltenborg5, Suzanne Dickson5, Dara Hedayatpour2,6, Catherine Stanton2,6, Gerard Clarke2,7, Siobhain M. O’Mahony1,2, Harriët Schellekens1,2 1. Department of Anatomy & Neuroscience, University College Cork, Cork, Ireland; 2. APC Microbiome Ireland, Cork, Ireland; 3. Instituto de Biomedicina de Sevilla, IBiS (Universidad de Sevilla, HUVR, Junta de Andalucía, CSIC), Sevilla, Spain; 4. Departamento de Bioquímica Médica y Biología Molecular e Inmunología, Facultad de Medicina, Universidad de Sevilla, Sevilla, Spain; 5. Department of Physiology/Endocrine, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, 405 30 Gothenburg, Sweden 6. Teagasc Food Research Centre, Moorepark, Fermoy, Co. Cork, Ireland 7. Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland.

An unhealthy diet during early-life can negatively impact offspring metabolic function and eating behaviour later in life. Microbiota-targeted interventions hold promise for the treatment of aberrant functioning of eating behaviour. This study evaluates the impact of an early-life high-fat/high-sugar (HFHS) diet on eating behaviour later in life, and whether this can be attenuated by microbiotatargeted strategies.

Male and female C57BL/6J mice were exposed to either control or HFHS diet from birth for 5 weeks.

Afterwards, all mice received control diet. Two groups with early-life HFHS diet were supplemented with a prebiotic (Fructo-Oligosaccharides+Galacto-Oligosaccharides, FOS+GOS) or a bacteria (B. longum APC1472) throughout. Meal pattern, saccharin and food preference were investigated at 6 and 11 weeks.

Five-week-old female and male pups exposed to early-life HFHS showed greater weight-gain compared to control pups with no microbiota-targeted intervention effects. Body weight was normalised after 12 weeks, after switching to control diet. Early-life HFHS diet increased meal size, eating rate and total HFHS intake in 11-week-old females. Early-life HFHS increased preference towards palatable food at 6 and 11 weeks in both sexes whilst simultaneously increasing food grinding behaviour. APC1472 alleviated HFHS-induced alterations in food preference and food grinding behaviour in both sexes.

APC1472 and FOS+GOS alleviated the alterations in meal pattern in females. Early-life HFHS diet induced molecular changes in key brain regions involved in eating regulation, including the hypothalamus and striatum.

These findings demonstrate that an early-life unhealthy diet has long-lasting, sex-specific effects on eating behaviour, which can be alleviated by microbiota-targeted strategies.

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Sex-specific socioeconomic inequalities in physical activity trajectories from late childhood to early adulthood: a prospective cohort study Prachi Sharma1, Farzana Ferdous1, Linda M O’Keeffe1,2,3, Ahmed Elhakeem2,3 1. School of Public Health, University College Cork, Ireland 2. MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK 3. Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK Cardiovascular disease (CVD) is a leading cause of death globally, with risk beginning in childhood and progressing into adulthood. Socioeconomic position (SEP) has a well-established relationship with CVD risk, but emerging evidence suggests that lower SEP may increase CVD risk more in females than males.

Physical activity (PA) is a critical modifiable risk factor for CVD, with PA patterns from adolescence tracking into adulthood.

This study aims to investigate sex-specific socioeconomic patterns in PA trajectories from childhood to early adulthood using data from the Avon Longitudinal Study of Parents and Children (ALSPAC). We used accelerometer-based measures of PA, including total activity, moderate-to-vigorous PA (MVPA), light PA (LPA), and sedentary PA (SED), collected at ages 11, 13, 15, and 24. SEP indicators (maternal and paternal education, and household social class) were used to examine their association with PA, controlling for relevant covariates. We applied multilevel models to explore sex-specific SEP differences in PA trajectories.

Initial findings suggest that socioeconomic disparities in PA vary by sex, with males generally more active than females. However, within each sex, these disparities in PA widen across SEP subgroups as age progresses, potentially increasing long-term cardiovascular risk.

These differences highlight the importance of considering both sex and socioeconomic factors when examining PA patterns over time. Understanding how these patterns evolve across socioeconomic groups could help inform the development of targeted interventions aimed at promoting PA during adolescence, which may contribute to reducing future cardiovascular risk, particularly in disadvantaged populations.

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Patterns of Sex-specific Socio-economic inequalities in e-cigarettes, traditional cigarettes and dual use among young adults: a prospective descriptive study.

Prachi Sharma1, Dr Zubair Kabir1, Linda M O’Keeffe1,2,3 1. School of Public Health, University College Cork, Ireland 2. MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK 3. Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK Background: Smoking is a major cause of preventable death globally, linked to chronic diseases like cardiovascular and respiratory disorders. The rise of electronic cigarettes (ECs) has altered smoking behaviours, especially among young adults. While socioeconomic position (SEP) disparities in traditional cigarette (TC) smoking are well-documented, less is known about such disparities among exclusive EC users and dual users (both TC and EC). This study investigates how SEP relates to smoking behaviours in young adults, with a focus on sex-specific differences.

Methods: Data were obtained from the Avon Longitudinal Study of Parents and Children (ALSPAC), a birth cohort in southwest England. The analysis involved 3,960 participants, assessing the association between SEP at birth (maternal education, paternal education, household social class, composite SEP) and smoking behaviours—non-smoking, exclusive vaping, exclusive smoking, and dual use—using logistic regression models. The analysis was stratified by sex.

Results: Of the participants, 33% were non-smokers, 2.2% were exclusive EC users, 33.7% exclusive TC smokers, and 30.2% dual users. Lower SEP was linked to higher smoking and dual-use rates, particularly among females. Higher parental education reduced the likelihood of dual use but increased TC smoking in some groups. Males with fathers holding degrees were 71% less likely to use ECs, while females with mothers holding degrees were 37% less likely to be dual users.

Conclusion: SEP impacts smoking behaviours in sex-specific ways. Higher SEP often protects against dual use but may increase TC smoking, especially among males. Public health interventions should address these socioeconomic and gender-based disparities.

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Targeted delivery of RNA-based therapeutics to the gut to modulate the JAKSTAT pathway in Crohn’s Disease Aman Saifi1,2,3 , Ken Nally1,3, Silvia Melgar1 1. APC Microbiome Ireland, University College Cork 2. Department of Medicine, University College Cork 3. School of Biochemistry and Cell Biology, University College Cork Crohn’s disease (CD) is a human immune-mediated inflammatory disease (IMID) of unknown etiology that affects the gastrointestinal (GI) tract. CD is now a global health issue due to its lifelong nature and significant burden on patients and public health [1]. Phase III clinical trials have shown that treatment with oral Janus Kinase (JAK) inhibitors can alleviate disease in patients with CD. However, the United States (US) Food and Drug Administration (FDA) has issued warnings about side effects for this class of oral drugs which target JAKs systemically in the human body. Therefore, new targeted delivery approaches are needed to block JAK activity selectively in the GI tract. The JAK1/2-STAT1 intracellular signaling pathway is activated by the Th1 cytokine IFN-γ alone or in synergy with another Th1 cytokine, TNF-α. This pathway activates the expression of inflammatory genes in multiple cell types typically associated with active or inflamed CD [2]. RNA interference (RNAi) mediated gene silencing through small interfering RNA (siRNA) is a promising method to silence the expression of disease-causing genes in the JAK-STAT pathway. The GENEGUT project aims to develop oral RNA-based therapies for ileal CD. In this study, we are developing new approaches to deliver siRNAs targeting JAK1, JAK2, and STAT1 into relevant cell models, including HEK-Blue IFN-reporter cells and human intestinal epithelial cell lines.

We have developed epithelial cell models that replicate the inflamed conditions in CD by exposing epithelial cells to inflammatory cytokines IFN- γ/TNF- α, leading to increased cytokine production and cell death. We have shown that selected siRNAs effectively blocked JAK1, JAK2 and STAT1 expression and activity, preventing the downstream activation of inflammatory and cell death pathways. Further studies will be conducted in differentiated monolayers, complex cell co-culture models and human primary intestinal organoids.

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Added Benefit of Triple Therapy for Cystic Fibrosis Patients with Phe508del– Gating Genotype: A Real-world Prospective Study.

Hisham I.S. Ibrahim1,2, Tom Farrell1, Mairead McCarthy1, John Dorgan1, Claire Fleming1, Ciara Howlett1, Karen Cronin1, Edel O'Riordan1, Janice Mansfield1, Sarah Twohig1, Yvonne McCarthy1,2, Tamara Vagg1,2, Kevin Deasy1,2, Barry J. Plant1,2 1. Cork Adult Cystic Fibrosis Centre, Cork University Hospital and University College Cork, Cork, Ireland.

2. HRB Clinical Research Facility, University College Cork, Cork, Ireland.

Due to Chronic inflammation and high prevalence of diabetes mellitus in people with cystic fibrosis (PWCF), the risk of cardiac events is higher in PWCF than age matched individuals.

Life expectancy is increasing in CF even before the rollout of the highly effective CFTR modulation therapy.

Given the known association between longevity and cardiovascular disease, the incidence of cardiovascular adverse events will likely increase further.

We assessed in a real-world setting the change in cardiometabolic risk factors post initiation of elexacaftor-tezacaftor-ivacaftor (ETI) in the first 61 CF patients homozygous/heterozygous for Phe508del mutation attending our clinic. In addition to standard clinical outcome measures, we measured the changes in lipid profile, HbA1c, and BMI at baseline and prospectively at 3- and 6months.

Consistent with clinical trial findings, the study data showed significant improvements in ppFEV1 (12.2%, P=0.002), sweat chloride (-39.3mmol/L, P<0.0001), post ETI treatment. At 6 months of ETI therapy the mean of differences in BMI was 1.06 (p= 0.042), 32.7% of patients had a BMI >25 at 6 months of therapy compared to 19.7% at the start of ETI therapy. The mean of difference in total cholesterol levels was 0.24 mmol/L (p=0.003), and mean low-density lipoprotein level increased from 1.97 mmol/L at baseline to 2.16 at 6 months of ETI therapy (p=0.003). The mean of difference in HbA1c was -1.885mmol/mol.

With the rollout of ETI, change in the nutritional management strategies in CF care, with a greater focus on the detection and prevention of cardiometabolic risk factors is increasingly important.

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Long-term real-world outcomes of CFTR modulation with Ivacaftor in adult cystic fibrosis patients with the G551D mutation; 8 years single center realworld study.

Hisham I.S. Ibrahim1,2, Kevin Deasy1,2, Mairead McCarthy1, John Dorgan1, Claire Fleming1, Noreen Tangney1, Ciara Howlett1, Karen Cronin1, Edel O'Riordan1, Janice Mansfield1, Sarah Twohig1, Yvonne McCarthy1,2, Tamara Vagg1,2, Desmond Murphy1,2, Barry J. Plant1,2 1. Cork Adult Cystic Fibrosis Centre, Cork University Hospital and University College Cork, Cork, Ireland.

2. HRB Clinical Research Facility, University College Cork, Cork, Ireland.

Clinical trials and real-world studies highlighted the benefits of ivacaftor in cystic fibrosis (CF) patients with G551D mutation. Data pertaining to the long-term effect of CFTR modulators beyond 5 years of treatment is limited.

We collected data at 8-years of ivacaftor treatment in 25 CF adults with G551D mutation. Clinical parameters including lung function, modified shuttle walk test, body mass index (BMI), exacerbations frequency, and sweat chloride were compared to baseline and 1 year of treatment.

The mean age was 30.5 years. The improvement in percent of predicted forced expiratory volume in 1-second (ppFEV-1) of 10.79% (p<0.0001) at year 1 was followed by a significant decline at 8-years (mean of differences -11.09% between 1- and 8-years, p=0.0005). The 68.43meters improvement in the modified shuttle walk test (p=0.021) seen at year 1 was lost at 8-years.

The significant reduction in sweat chloride is sustained at 8-years (mean of difference -58.12mmol/L and -52.44mmol/L at 1 and 8-years of treatment, respectivel y, p<0.0001). The mean BMI improved from 20.28 at baseline to 21.76 at 1-year, to 22.7 at 8-years.

The mean exacerbation frequency at 1-year of treatment dropped from 1 to 0.17 (p=0.0048), but increased to 0.66 at 8-years (p=0.038).

In a cohort of adult CF patients, the initial improvements in lung function, walk test and exacerbations frequency seen at 1-year of ivacaftor treatment were not sustained at 8-years. Understanding the factors influencing long term effectiveness of CFTR modulation is paramount to prolong the initial beneficial effects and improve survival in CF.

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Crying out over spilt milk: Quantifying formula milk waste in a large maternity hospital Maura Hannon1, Eileen O’Leary2, Veronica Daly1, Cathy Burke1 1. Department of Obstetrics and Gynaecology, Cork University Maternity Hospital, Cork, Ireland 2. Clean Technology Centre, Munster Technological University, Cork, Ireland Introduction: Healthcare generates 5% of global carbon emissions, and its reduction will be a key part of meeting global carbon emission targets. Infant formula is an ultra-processed food with a large carbon footprint.

Aim: We aimed to measure infant formula waste at Cork University Maternity Hospital (CUMH). This was achieved by measuring the volume of milk and plastic bottles disposed of over a 5-day period.

Results: Our findings showed that an average of 4.7L of infant formula was discarded each day.

Extrapolated figures estimate that 1,716L of formula are discarded per year in CUMH. This is equivalent to 23,568 full 70 ml formula milk bottles being discarded every year. The carbon footprint of this wasted formula is just over 18 tonnes (18,150kg) CO2 equivalent emissions annually, rising to almost 19 tonnes when the carbon footprint of the plastic bottles is included. The is an estimated cost of €12,200 per year.

Discussion: Strategies to reduce infant formula waste include greater encouragement of breastfeeding, decanting more appropriate volumes of formula milk from larger containers into sterile formula bottles, using reconstituted powdered milk and working with formula milk producers to reduce the volume of ready-to-use newborn infant formula bottles from 70mls to 40 or 50mls.

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Investigating Mechanistic PRedictors Of interpatient Variability and temozolomide (TMZ) induced haematological toxicity for glioma patients (IMPROVE TMZ) Barbara Collins1, Maria Donovan2, Darren Crowley2, Erin K. Crowley1,3, Richard M. Bambury1,3, Laia Raigal-Aran1,3, Roisin M. Connolly1,3, Jack P. Gleeson1,3 1. Cancer Research @UCC, College of Medicine and Health, UCC, Cork, Ireland 2. Pharmaceutical Care Research Group, School of Pharmacy, UCC, Cork, Ireland 3. Cancer Trials Cork, CUH/UCC Cancer Centre, Cork University Hospital, Cork, Ireland Background: Concurrent (with radiotherapy) and adjuvant temozolomide (TMZ) is the standard of care treatment for high grade glioma, however, severe haematological toxicity is a major dose limiting factor, impacting 16-45% of patients in different studies. We hypothesize that mechanistic factors such as genetic polymorphisms, renal function or other patient factors such as sex, concomitant medications or the gut microbiome result in this interpatient variability in toxicity. We aim to develop a pharmacokinetic model of temozolomide to test the effect of these potential covariates on TMZ concentration (Part A) in patients with brain tumours being treated with TMZ. Using this model, we aim to assess patients who develop haematological toxicity from TMZ for mechanistic predictors of this toxicity (Part B).

Methods: This is a translational, prospective, observational study.

For Part A, 35 patients with a high grade glioma receiving TMZ will be enrolled. Data will be collected on patient characteristics as well as research blood samples to measure TMZ concentration in plasma, buccal swab to test for pharmacogenetics which may affect TMZ concentration, and stool sample to determine if the microbiome changes during treatment and is linked with haematological toxicity.

For Part B, 20 patients who have developed haematological toxicity during treatment with TMZ will be enrolled. Data will be collected on patient characteristics and a buccal swab to test for relevant pharmacogenes.

For both parts A and B, pharmacogenetic testing of archival tumour samples may be conducted to determine if the buccal swab reflects the tumour pharmacogenetics.

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Developing non-coding synthetic circular RNA tools for modulation of gene and protein expression in sepsis Meaghan Richardson1,2; Nerea Hernandez Egido1,2; Kellie Dean3, Piotr Kowalski1,2 1. School of Pharmacy, UCC 2. APC Microbiome 3. School of Biochemistry and Cell Biology, UCC Sepsis is the life-threatening organ dysfunction caused by a dysregulated host response to infection that globally affects over 48.9 million people and results in 11 million deaths annually. Currently, no treatments exist which effectively target pathways involved in sepsis progression, contributing to unacceptably high mortality. In nature, circular RNAs (circRNAs) function as sponges sequestering microRNAs (miRNAs) to control protein expression and modulate multiple cellular pathways. Inspired by these natural circRNAs, we seek to develop synthetic circRNA miRNA sponges engineered to specifically modulate the biological pathways implicated in sepsis. As a proof of concept, synthetic circular RNA miRNA sponges were constructed containing repeat binding sites targeting miR-155, a miRNA that is constitutively expressed in HUVECs.. We have generated circRNA sponges with 12 miR155 binding sites and have designed constructs with up to 60 miR-binding sites. To minimise immunogenicity of circRNA products, HPLC-based purification strategies were optimized and evaluated in vitro. The design and efficacy of these sponges will be evaluated in vitro using a NanoLuc reporter assay. Future work will incorporate sepsis-specific target miRNAs and evaluate the therapeutic intervention in vivo.

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Understanding COPD mortality in Cork University Hospital 2022-2023. HIPE vs Reality.

Mairead O’Donnell1, Hisham Ibrahim1,2, Fernando Gomez1,2, Anne O’Mahony1,2, Desmond Murphy1,2, Barry Plant1,2, Kevin Deasy1,2 1. Department of Respiratory Medicine, Cork University Hospital.

2. School of Medicine, University College Cork.

Background: Chronic Obstructive Pulmonary Disease (COPD) accounts for 3% of deaths worldwide. In Irish hospitals deaths from all causes are coded 1and reported centrally to the National Office of Clinical Audit (NOCA).

Methods: To compare actual HIPE coded, NOCA reported COPD mortality at Cork University Hospital between January 2022 and December 2023, with an expert panel review by Senior Consultant Respiratory Physicians (n=4) of medical notes/electronic records/post-mortem results in the same cohort, to determine levels of concordance. Relevant to physician assessment, we did not characterise a death from a definitive ‘Pneumonia” as a primary diagnosis of death from COPD exacerbation.

Results: NOCA reported a total number of n=59 deaths from COPD exacerbation over the two-year period. Expert panel review suggested that 34% (n=20/59) met this criteria and of those who did not 66% (n=39/59), 54% were diagnosed with pneumonia (n=21/39). In 42% of cases (n=25/59), COPD was a co-morbidity rather than a principle cause of death. A definite COPD diagnosis could not be established in 24% of cases (n=14/59).

Conclusions: Significant discrepancies in COPD mortality rates exist between national statistical reporting mechanisms and expert panel review, with the potential to misinform healthcare planning strategies.

Keywords: COPD, mortality.

Conflict of Interest: The authors declare that they have no conflict of interest.

OECD (2023), Health at a Glance 2023: OECD Indicators, OECD https://doi.org/10.1787/7a7afb35-en.

Publishing,

Paris,

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Investigating L cells as cross-barrier signal transducers of microbiota-gut-brain communication Clíona O’Connor1,2,3, Lauryn Gbemisola Adewale4, Mark Rae1,2, Dervla O’Malley1,2,3 1. Department of Physiology, University College Cork, Ireland 2. School of Medicine, University College Cork, Ireland 3. APC Microbiome Ireland, University College Cork, Ireland 4. School of Bioscience, University of Skövde, Sweden Background: Communication across the microbiota-gut-brain axis is integral to homeostatic functions throughout the body, yet the mechanisms behind it are still unclear. L cells are located at the intersection of the gut barrier, and the host endocrine and neural systems. These cells release GLP-1 basolaterally following stimulation by nutritional, microbial, or liver products, with effects seen in both the gastrointestinal tract (GIT) and brain.

Hypothesis: GLP-1 is a key signalling molecule in intestinal cross-barrier communication between the distal microbiota and the host, and its signalling can be altered be PUFA-containing bacterial secretions.

Methods: Immunofluorescent imaging, calcium imaging, and ELISA were used to examine the effects of B. breve 2258 secretions on receptor expression, cellular activation, and GLP-1 secretion in NCIH716 cells, a human-derived model of L cells.

Results: Acute exposure to PUFA-containing B. breve secretions increased intracellular calcium and nuclear cFOS expression in NCI-H716 cells but did not stimulate GLP-1 secretion following a 2-hour incubation. Exposure to B. breve secretions resulted in increased cellular expression of GLP-1 receptors and FFAR4. Interestingly, exposure of cells to B. breve supernatants in the presence of GLP-1 receptor and FFAR4 antagonists resulted in considerable GLP-1 secretion.

Conclusion: PUFA-containing bacterial secretions activate GLP-1-secreting cells, yet did not stimulate GLP-1 secretion. The increase in GLP-1 secretion upon inhibition of GLP-1 receptors and FFAR4 indicates a possible regulatory mechanism. Further research is required to understand the molecular mechanisms underpinning stimulation of host L-cells by bacterial products and how that impacts gut function and gut-to-brain signalling.

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The role of voltage-gated calcium channels in oesophageal adenocarcinoma Ciara Gavin1, Sharon McKenna2, Tracey O’Donovan2, John Mackrill1 1. Department of Physiology, UCC 2. Cancer Research @UCC, College of Medicine and Health, UCC Five-year survival for oesophageal adenocarcinoma (OAC) is <20% across the EU and new therapeutic options are required. We examined transcriptome data of calcium signalling genes from two OAC patient databases. High expression of L-type voltage-gated calcium channel (L-VGCC) subunit genes CACNA1D and CACNA2D4 was associated with significantly better five-year survival. The mechanism underlying this is unknown.

We aim to examine the expression of these proteins in an OAC cell line panel and assess their activity.

We will then assess their role in cancer cell viability.

Using Western immunoblotting, CACNA2D4 protein was detected in OE19, OE33, and FLO-1 OAC cell lines at variable levels. Of five oesophageal squamous cell carcinoma cell lines tested, CACNA2D4 protein was only detected in KYSE-270.

Fura-2 Ca2+-indicator assays were used to study channel activity. FLO-1 cells were treated with 100 μM Bay K8644, a L-VGCC agonist, causing a significant rise in Ca2+ (p < 0.001) indicating functional LVGCCs. This rise was not observed in OE19 cells. L-VGCCs may not be functional in these cells, or it may have other activity that we are not measuring.

The effect of Bay K8644 and nifedipine (a L-VGCC antagonist) on OAC cell viability was investigated using resazurin reduction assays. 10–100 μM of either reduces OE19 and FLO-1 viability over 24 hours in a concentration-dependent manner. We will assess whether this is related to their calcium channel activity.

We hope that this research will translate into improved treatment for OAC patients with the existing repertoire of approved calcium modulating agents.

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A study within a study: Logistics of patient sample acquisition in academic clinical microbiome studies: Identification of determinant factors of success.

Ciarán Devoy1, Prof Mark Tangney1,2 1. Cancer Research @UCC, College of Medicine and Health, University College Cork, Ireland 2. APC Microbiome Ireland, University College Cork, Ireland Introduction: Clinical microbiome-wide association studies (MWAS) are crucial for understanding the relationship between gut microbiota and cancer. However, the success of these studies is heavily influenced by factors such as study setup (SU), patient management (PM), and sample acquisition. This research investigates the determinants of successful patient and sample acquisition across three hospitals, focusing on the impact of team structure, patient flow, and recruitment strategies.

Methods: Three MWAS Clinical Observational Studies (COS) were established in collaboration with one private and two public hospitals. Data from these sites were collected and analysed, focusing on team composition, patient recruitment, and sample collection dynamics.

Results: Variations in team hierarchy and size significantly influenced SU timelines and patient/sample accrual rates. Site C, characterised by a proactive recruitment strategy and continuous patient flow, achieved the highest patient and sample acquisition rates, outperforming Site A, which terminated early, and Site B, which showed a staggered recruitment pattern. Delays in SU were common across all sites, primarily due to regulatory and team dynamic issues. Notably, the involvement of dedicated research nurses during the PM phase was correlated with higher sample acquisition rates.

Conclusion: This study identifies key factors affecting the success of clinical microbiome studies, emphasising the importance of efficient team structures, proactive recruitment strategies, and dedicated clinical personnel. These findings offer valuable insights for optimising logistics in future academic clinical microbiome research. This is the first study to systematically analyse such data in an Irish context.

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A quality improvement project to enhance implementing regulatory protocol amendments in a radiotherapy clinical trials department at the Bon Secours Radiotherapy Centre Cork in partnership with UPMC Hilman Cancer Centre.

Karen P. Molan1,2, Caoimhe Buckley1,2, Erica Bennett1,2, Dr. Paul J. Kelly1,2 1. School of Medicine, UCC. 2. Bon Secours Radiotherapy Cork in Partnership with UPMC Hilman Cancer Centre.

Background: Radiation oncology clinical trials management require rigorous adherence to regulatory standards to ensure patient safety and data integrity of radiotherapy clinical trials are maintained. All clinical trial activity must be conducted in compliance within the regulatory approved protocol.

However, sometimes changes need to be made to the protocol or other trial documents after they have received the initial regulatory approval. These changes are called amendments. An amendment can take a significant amount of time and resources for site staff to review and implement at participating sites. This can affect the efficient delivery of clinical trials and potentially contribute to research waste.

Problem: Clinical sites are informed frequently from sponsor companies, of protocol amendment updates for studies. These are then required to be implemented in practice in a timely manner.

Solution: A comprehensive workflow was created to help streamline the protocol amendment implementation process and to therefore improve regulatory compliance and efficiency within the radiation oncology clinical trial department.

Results: The implementation of the protocol amendment workflow has resulted in a significant reduction in the time required to review, prepare, implement, and train staff members. Additionally, the workflow has helped to identify potential regulatory risks early in the amendment introduction process, allowing for proactive mitigation strategies.

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Genetic Therapies for Rare Disease Ciaran M. Lee1, Alexander Brennan1 1. School of Biochemistry and Cell Biology, UCC The patient population for any given rare disease is quite small; however, there are over 10,000 rare diseases representing 30 million people affected in the EU and over 400 million people worldwide.

Few of these diseases are preventable or curable, most are chronic, and many result in premature death. Their low prevalence results in a lack of knowledge and scarcity of expertise which when coupled with their chronic degenerative and life-threatening nature has led to rare diseases emerging as a public health priority in Europe. For many of these diseases a sound genetic basis has been identified with 4,805 genes associated with 7,379 diseases which has led to these diseases becoming the focus of gene-based therapies. The first gene editing therapy Casgevy has recently been approved for use in patients with sickle cell disease or beta thalassemia. While developing systems to correct individual mutations could treat inherited disease, the large variation in mutations that can cause a single disorder makes this approach impractical in many cases, for example, over 2,000 mutations have been identified in a cohort of 88,000 patients with the inherited disorder cystic fibrosis (CF). To address this challenge our lab is developing serine recombinase based systems to integrate therapeutic transgenes into safe harbour sites within the human genome. This next generation gene editing approach has the potential to correct the primary genetic defect irrespective of the causative mutation making this a viable approach for clinical translation.

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Identifying potential synergistic effects of retinoic acid and kinase inhibitors in glioblastoma cells Ellen Power1, André Toulouse1, Collette Hand2 1. Department of Anatomy & Neuroscience, School of Medicine, Unitversity College Cork 2. Department of Pathology, School of Medicine, University College Cork Approximately 80% of malignant primary brain tumours diagnosed are gliomas. The prognosis for stage 4 glioma, or glioblastoma, is poor with a 5-year survival rate of 5%. Further research is imperative to develop more effective treatments. One possibility would be to induce terminal differentiation of cancer cells to reduce their proliferation rate and render them more susceptible to treatment.

Retinoic acid (RA), a derivative of vitamin A, has pleiotropic effects in the body, and influences cell proliferation and differentiation, which are dysregulated in tumorigenesis. It is effective at inducing cell differentiation in other malignancies, but effects are less clear in glioblastoma.

Kinase signalling pathways are signal-transducing cascades playing roles in cell proliferation, survival, differentiation and death. Inhibition of these pathways have shown promise in glioblastoma treatment; however, it has been noted that monotherapies trialled in patients are largely ineffective.

RA has been documented to regulate certain kinase pathways. We hypothesise that combination treatments with RA and kinase inhibitors could reduce cell proliferation in glioblastoma.

Using the A172 glioblastoma cell line, the growth effects of RA and kinase inhibitors alone or in combination were assessed. Results indicate a synergistic effect between RA and inhibitors of the PI3K, AKT and ERK1/2 pathways. The combination treatments targeting these pathways were found to be more effective in reducing cell growth compared to RA or the inhibitors alone. Although further research is needed, these results highlight a potential therapeutic avenue for patients by simultaneously targeting these pathways.

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Exploring different sampling techniques to best characterise the airway microbiota in people with CF (pwCF) on ETI (elexacaftor/tezacaftor/ivacaftor) with prior P. aeruginosa (PA) colonisation Deasy, KF1,2, O’Brien, S3, Madden E1, Einarsson, GG3, McCarthy Y,2 Fleming C1, McCarthy M1, Dorgan J1, Gilpin DF3, Murphy DM2, Ibrahim H1,2, Tunney MM3, Plant, BJ1,2 1. 3CF, Department of Respiratory Medicine, Cork University Hospital, Cork, Ireland 2. HRB Clinical Research Facility Cork, University College Cork, Ireland 3. School of Pharmacy, Queen’s University Belfast, Belfast, UK Background: Microbiological surveillance is challenging in pwCF on ETI, as many become nonproductive or have a significant reduction in sputum volume/quality. In non-productive patients cough swabs have been used, as a surrogate for microbiological assessment. To date, results from studies determining the effect of modulator therapy on the CF airway microbiota have lacked consistency. This real-world observational study simultaneously assessed different accepted sampling methods to understand how best to prospectively characterise the airway microbiota of pwCF on ETI. Methods: Adult pwCF, with chronic PA prior to ETI initiation, who had completed at least 12-months of ETI therapy and were either non-productive or had objective reduction in sputum volume/quality were recruited. Matched samples of saliva, cough swab, induced sputum and bronchoalveolar-lavage (BAL) were collected. Regular inhaled antibiotics were held for a minimum of 4-weeks prior to assessment.

Results: Results on the first 25 subjects is presented. Median age was 31 with a ppFEV1 of 85%. 4 subjects were entirely non-productive, sputum was generated by spontaneous expectoration (n=2/25) and induced sputum (n=19/25). PA detection: not detected in any sputum samples, detected in1 subject with throat swap, and 2 subjects by bronchoscopy. A 6-lobe wash detected the most unique pathogens by standard culture (n=17). 61% (14/23) pathogens required bronchoscopy for detection by standard culture. There were no significant adverse events due to bronchoscopy.

Conclusion: Bronchoscopy is safe and feasible for airway monitoring in adult pwCF. Our preliminary results suggest that a select cohort of pwCF may clear chronic PA infection post-ETI.

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Consulting Marginalised Communities and Minority Groups to inform a National Inclusion Health Framework Dr Helen Kelly1,6, Dr Máiréad Harding2,6, Mary Cronin3,6, Dr Anne-Marie Martin4,6, Dr Eoin Coughlan5,6, Dr Alan Connolly4,6, Dr Angela Flynn4,6 1. School of Clinical Therapies, UCC 2. School of Dentistry, UCC 3. School of Public Health, UCC 4. School of Nursing and Midwifery, UCC 5. School of Medicine, UCC 6. Inclusion Health Research Group, UCC Inclusion health (IH) is a service, research, and policy agenda to prevent and redress health and social inequalities. The Department of Health (DoH) is developing the first national Inclusion Health Framework which aims to ensure future healthcare policy and practices take an IH approach. The DoH has contracted the CoMH Inclusion Health Research Group to undertake public consultations to inform the development of this framework.

This is a three-phase mixed-methods public consultation study. Phase 1 - establishment of a Lived Experience Advisory Panel (LEAP) (people with experience of social exclusion and health inequities), and a Professionals Advisory Panel (PAP) (professionals supporting marginalised groups in statutory health services, community, and voluntary sector organisations). These panels will guide important aspects of the consultation process. Phase 2 – development of a co-designed questionnaire through extensive consultation and feedback with LEAP, collected verbally and through a structured feedback form. This questionnaire will collect information about people's experiences of health services and identify the elements of an inclusive healthcare system they consider important. Phase 3 – Regional World Café and focus group consultations to explore the lived experience of healthcare-related social exclusion from the perspectives of individuals, representative organisations and Section 39/HSE professionals. Recommendations for more inclusive healthcare policies and services will be gathered.

We will present our methods of recruitment and engagement with these different priority groups under the IH umbrella. Additionally, we will share our experiences and learnings from working with LEAP and the importance of including people with lived experience in inclusion health development.

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How are direct healthcare professional communications (DHPC) operationalised by General Practitioners (GPs) and community pharmacists in Ireland?

Dr. Paul Ryan1, Dr. Ann Doherty1, Dr Darren Dahly2, Prof. Stephen Byrne3, Prof. Emma Wallace1 1. Department of General Practice, School of Medicine, University College Cork 2. HRB Clinical Research Facility, University College Cork 3. School of Pharmacy, University College Cork Background: Direct Healthcare Professional Communications (DHPCs) are issued by medicines regulators i.e. European Medicines Agency / the Health Products Regulatory Agency (HPRA), to update healthcare professionals of novel important safety information in a timely manner. However, international evidence suggests variation in their implementation in clinical practice and no studies have examined how DHPCs are actioned once received by primary care healthcare professionals.

Aim: To explore how primary care healthcare professionals operationalise DHPCs and their preferences for receiving medicines safety updates.

Methods: National cross-sectional survey of GPs and community pharmacists, developed in collaboration with the HPRA and conducted in June 2024.

Results: A total of 277 GPs and 219 community pharmacists completed the survey, representing 7.9% and 4.5% of the national registers, respectively. A total of 228 (82%) of administrative staff in GP practices opens the DHPC compared with 152 (69%) of pharmacists themselves opening the letter.

Barriers to implementation across both professional groups include time constraints, updates not being perceived as relevant, lack of notifications from practice software and many updates not perceived as relevant. A total of 230 (83%) GPs are willing to receive remote support from a GP/pharmacist to help implement recommendations compared with 164 (75%) pharmacists. A total of 257 (93%) GPs and 198 (90%) pharmacists asked that prescribing software systems give significant safety notifications.

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Medical Students’ Perspectives on Oncology in the Undergraduate Curriculum: a Cross-Sectional Study Neve Gavin1, Aislinn Joy2 1. School of Medicine, UCC 2. Medical Education Unit, School of Medicine, UCC 1 in 2 Irish people will develop cancer during their lifetime. An undergraduate oncology curriculum should reflect the needs of an ageing society and empower future generations of practitioners to provide comprehensive healthcare.

Aim: To explore medical students’ perceptions of undergraduate oncology education, with the following objectives: i) characterise the studied population, ii) evaluate student exposure to oncology (e.g. lectures, specific skills), iii) survey students’ attitudes towards the current oncology curriculum, iv) survey students’ views of oncology, and v) assess factors that affect students’ views of oncology education.

Methods: Following ethical approval, a quantitative survey was distributed electronically to direct- and graduate-entry UCC medical students. The data was prepared with Microsoft Excel and analysed using UCC-licensed SPSS. Results: 124 students completed the questionnaire (33% were male, 67% female). Direct-entry students accounted for 78% of responses and graduate-entry students the remaining 22%. DEM4 students had the highest response rate (26% of responses) across all years. The median respondent age was 21 years.

Most reported minimal knowledge of cancer, poor confidence in various aspects of clinical oncology, and dissatisfaction with the current curriculum. 28% of respondents were satisfied with the content and material of preclinical oncology teaching (years 1-3), whilst 19% were satisfied with the content and material of clinical oncology teaching (years 3-5). 89% agreed that oncology is a challenging specialty.

Conclusion: Students’ dissatisfaction with current oncology teaching, along with their expressed views toward various aspects of oncology, establish a need for further development and enhancement of the undergraduate oncology curriculum.

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Insights from Analysis of Uropathogenic Escherichia coli Whole Genome Sequences from Cork University Hospital Niall PG Busher1, Sinead Kilgarriff2, Jane O'Connor2, Niall O'Mara2, Edward McCullagh2, Aisling O'Shea2, Louise Barry2, Deirdre Broderick2, Conor Deasy3, Zihao Wang4,5,6, Clara Kampik4,5,6, Mark Tangney6, *Michael B Prentice1,4,5 (*presenting author) 1. School of Microbiology, College of SEFS, UCC 2. Department of Microbiology, Cork University Hospital 3. Department of Emergency Medicine, Cork University Hospital 4. Department of Pathology, College of Medicine and Health, UCC 5. APC Microbiome Ireland, UCC 6. Cancer Research@UCC, College of Medicine and Health, UCC Escherichia coli strains are the predominant cause of urinary tract infection, the most commonly diagnosed bacterial infection. Urinary tract infection is a common cause of systemic sepsis, and E.coli is now the commonest bloodstream infection isolate, exhibiting increasing antimicrobial resistance.

We used whole genome sequencing (WGS) to analyse 45 E.coli strains isolated from urine from patients with clinical urinary tract infection presenting at Cork University Hospital in 2023-4. The objectives were to determine genetic features of the prevalent bacteria and their plasmids, particularly those associated with antimicrobial resistance. One strain was found to be Escherichia marmoti, a recently recognised Escherichia species phenotypically very similar to E.coli. Concordance between bioinformatic predictions and phenotypic antimicrobial resistance was high for Trimethoprim and Aminoglycosides. Systematic over-prediction of colistin resistance from gene sequence was associated with phylogroup. A minority of strains contained multiple bacterial microcompartment operons in addition to the canonical ethanolamine utilisation operon. Over 40% of strains contained genes specifying a dihydroxyacetone phosphate (DHAP) shunt, recently suggested to be a feature of Extraintestinal Pathogenic E. coli (ExPEC). In comparison with previously published studies on urinary isolates taken from the same hospital in 2015 and 2019, an increase in the percentage of strains assignable to Phylogroup B2 (mainly the internationally successful sequence types (ST) ST131, ST69 and ST73) was seen. Some ST69 and ST95 strains differing by very few core genome single nucleotide polymorphisms (SNPs), and some plasmids, were persistent (present in more than one time period).

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An Investigation into Factors Influencing Recognition of Prescribing Cascades Amongst Medical Hospital Doctors.

Ruth Daunt1,2, Kieran Dalton3, Denis Curtin2, Denis O'Mahony1,2 1. School of Medicine, University College Cork 2. Department of Geriatric & Stroke Medicine, Cork University Hospital 3. School of Pharmacy, University College Cork Introduction: A prescribing cascade occurs when a medication is prescribed to treat a side effect of another medication. Despite being well described for nearly three decades, there remains a concerning lag between academic knowledge and addressing prescribing cascades in clinical practice.

This study aims to explore the behavioural domains affecting knowledge and recognition of prescribing cascades amongst hospital medical doctors.

Methods: Qualitative semi-structured interviews were conducted between May and July 2024 with hospital medical doctors of all grades and specialties. Interviews were audio-recorded and transcribed verbatim. Interviews were coded according to the Theoretical Domains Framework (TDF).

Results: Fourteen doctors were interviewed. Three main themes emerged: (i) Knowledge- doctors demonstrated limited conceptual knowledge of prescribing cascades. (ii) Social/ professional role- the necessity of a collaborative approach involving patients, doctors, pharmacists, and other healthcare professionals to ensure accurate medication reconciliation, recognition of adverse events and communication between stakeholders. (iii) Environment- there is a lack of infrastructure/ supports/ team continuity. Without appropriate supports, such as an integrated system with the community, addressing prescribing cascades can be too difficult and can be deferred to the next doctor.

Conclusion: This study highlights significant gaps in the knowledge and understanding of prescribing cascades among hospital medical doctors, compounded by multiple environmental barriers, such as lack of electronic health records, time constraints, and lack of team continuity. Intervention to improve the recognition and management of prescribing cascades should involve all stakeholders, address educational needs, and infrastructure improvements.

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Microbial metabolites suppress the tumour promoting functions of IL-36 cytokines in colorectal cancer Méabh Finucane1,2, Jonathan Keane1, Elizabeth Brint2, Aileen Houston1 1. Department of Medicine, School of Medicine, UCC 2. Department of Pathology, School of Medicine, UCC The IL-36 cytokines are a subset of the IL-1 family of cytokines, comprising of three agonists, (IL36α/β/γ), two antagonist (IL-36Ra and IL-38) and a receptor (IL-36R). Similar to other IL-1 family members, IL-36 cytokines have complex functions in cancer, exhibiting both pro- and anti-tumorigenic functions. Microbial metabolites similarly have dual functions in colorectal cancer (CRC). For instance, butyrate, a SCFA displays tumour suppressive activity, deoxycholic acid (DCA) is a secondary bile acid with potential pro-tumorigenic functions and γ-aminobutyric acid (GABA) is a product of several bacterial species with anti-tumorigenic functions in CRC. This study aimed to investigate if microbiome-encoded metabolites alter the pro-tumorigenic activity of IL-36 cytokines in CRC. Cell proliferation, migration, gene expression and signalling were assessed by resazurin reduction assay, wound scratch assay, qRT-PCR and Western Blot respectively.

Stimulation of human HT29 cells with IL-36β/γ (100ng/mL) increased cellular proliferation, and migration in vitro. While cell stimulation with each metabolite alone (1mM butyrate, 25µM DCA and 50µM GABA) had little effect, co-treatment with both butyrate and DCA (separately) significantly suppressed IL-36 induction of these tumorigenic processes. Co-treatment with GABA suppressed IL-36 mediated proliferation, however, migration increased. Western blotting for intracellular signalling pathways involved in IL-36-mediated proliferation revealed butyrate and IL-36γ co-treated cells expressed decreased phosphor-RPS6, potentially implicating the AKT/mTORC1 pathway. Both butyrate and DCA modulated IL-36-induced cytokine and chemokine production.

These studies have shown that the pro-tumorigenic functions of IL-36 cytokines are suppressed by butyrate and DCA, suggesting bidirectional interaction with the microbiota may impact the activity of IL-36.

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Behavioural Assessment of Neuropsychiatric Outcomes in Rodent Stroke Models: A Systematised Review Robert M Callaghan1,2, Huiyuan Yang1,2, Rachel D Moloney1,2,3, Christian Waeber1,2 1. School of Pharmacy, University College Cork 2. Department of Pharmacology and Therapeutics, School of Medicine, University College Cork 3. APC Microbiome Ireland, University College Cork Stroke is a major cause of disability, with well-known consequences such as aphasia and motor dysfunction. Mood disorders following stroke are much less recognised, even though ~30% of survivors suffer from post-stroke depression, and 20% suffer from post-stroke anxiety. Most experimental stroke studies focus on the sensorimotor sequalae of stroke, while fewer studies assess the effect of stroke and/or interventions on non-sensorimotor functions including neuropsychiatric disturbances. We quantified this disparity by screening peer-reviewed papers published over the last twenty years. Of the 965 papers included in our review, 932 (97%) included sensorimotor testing, while 137 (14%) included non-sensorimotor testing. The most popular non-sensorimotor tests were the Morris water maze, open field, Y-maze, and novel object recognition tests. Disparities in the neuropsychiatric domain assessed by these tests were noted, with cognition being assessed in the majority (70%) of non-sensorimotor tests employed, followed by anxiety (27%), and depression in a small minority of papers (3%). Potential confounding factors and challenges for accurate interpretation of data were also identified in the most prevalent tests (the Morris water maze, open field test, and novel object recognition test). While our review confirmed disparity between sensorimotor and non-sensorimotor testing in experimental stroke research, it also shows that the share of the studies including the latter is increasing. Given the impact neuropsychiatric disorders have on stroke survivors it is essential that research into the neuropsychiatric sequalae of stroke continues to increase (in particular depression), while also addressing methodological issues with such testing as noted in this review.

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Introducing A New Treatment Protocol to CUH: An Audit of the Practical Experience Peter Doyle1,2, Lorna Power3, Emma Lane3, Eoghan Molloy3, Derville O’Shea3, Mary R Cahill1,3 1. HSE eHealth Hub 2. School of Medicine, UCC 3. Cork University Hospital, Cork Introduction: Venetoclax plus Obinutuzumab (Ven-O) is a fixed-duration first-line treatment for TP53intact Chronic Lymphocytic Leukaemia (CLL), with risks of tumour lysis syndrome (TLS) and cytopenias necessitating close monitoring by clinical nurse specialists (CNS). Since April 2022, we have treated 32 patients at Cork University Hospital (CUH) using the NCCP-approved Ven-O protocol, which includes a 5-week venetoclax ramp-up. This audit evaluates the real-world experience of adopting this protocol.

Materials and Methods: Retrospective data from April 2022 to March 2024 was collected from the Dedalus APEX laboratory system, Aria Oncology Information System, and iSoft Clinical Manager (iCM).

Patient demographics, TP53 and IgHV status, laboratory and radiology results were analyzed. Our patient data was compared to published studies.

Results: Thirty-two patients (24 males, 8 females) aged 43-79 years (median 66.5) received Ven-O. Median time from diagnosis to treatment was 46 months. Indications for treatment included thrombocytopenia (10 patients), anaemia (13), immune phenomena (11), splenomegaly (10), and B symptoms (7). OS was 90%, with 1 AML case and 2 Richter’s transformations, all fatal. One patient discontinued due to steroid-related psychosis. Haemoglobin levels normalized in patients with initial Hb <10g/dL, and platelet counts improved in 23% with initial thrombocytopenia. Neutropenia occurred in 16 patients, peaking at 21% in the first 4 months, with most cases being mild.

Discussion: Ven-O is effective as an outpatient therapy for CLL, with most patients responding well.

CNS support is critical for managing this protocol.

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Investigating the potential of whey proteins as a treatment for modulation of appetite using FED3.1 devices Friederike Uhlig*1,2,3, Alice Kellaghan*1,2, Nathan Carey*1,2, Andrea Pignatelli Espejo1,3, Harriët Schellekens1,2,3 1. Department of Anatomy and Neuroscience, UCC 2. Food for Health Ireland 3. APC Microbiome Ireland, UCC * authors contributed equally Loss of appetite is a major health concern in an ageing population. It increases the risk of malnutrition, and, particularly when associated with weight loss, leads to increased chance of developing frailty, disability, and mortality. Appetite stimulating medication on the market can have serious side effects such as blood clotting that warrant discontinuation. Ghrelin is an important orexigenic peptide that induces food intake through activating ghrelin receptors (GhSR). We have previously shown that hydrolysed whey proteins activate the ghrelin receptor in-vitro and increase food intake in rats. Here, we tested whether non-hydrolysed whey proteins exert similar effects.

Intact whey proteins were assessed for their ability to activate GhSR using Calcium mobilisation assay in HEK293 cells over-expressing GhSR. Two out of three candidates profoundly activated the ghrelin receptor. After stimulated in-vitro digestion, their activity increased. We then tested whether there was a correlation between in-vitro ability to activate the receptor and increasing food intake in-vivo.

Adult male and female mice were gavaged with whey proteins (50 mg/Kg) in the morning and food intake quantified either using “Feeding Experimentation Devices” (FED3.1) or manually for 24-hour periods over 7 days. None of the candidates significantly altered food intake over 24 hours. However, in depth analysis of meal patterns revealed sex-specific differences. Administration of whey proteins did not modify body weight, blood glucose levels or stomach weight. Interestingly, mice consumed significantly more food on FED compared to non-FED days.

These results suggest that pre-hydrolysis is required to generate bioactive compounds modulating food intake in-vivo.

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Characterization of Oxytocin Gene Expression in the Mouse Gastrointestinal Tract and Sensitivity to Microbial Disruption Alice Kellaghan1, Nathan Carey1, Carla Viñola-Renart1,2,3, Harriët Schellekens1,3, Niall P. Hyland2,3, Friederike Uhlig1,3 1. Department of Anatomy and Neuroscience, UCC 2. Department of Physiology, UCC 3. APC Microbiome Ireland, UCC Oxytocin is an important neuropeptide that regulates multiple physiological processes including gastrointestinal function and inflammation. Although known to be produced in the hypothalamus, oxytocin expression has been described in the gut and other peripheral tissues. Yet, little is known about factors regulating its expression. Administration of specific bacteria modulates oxytocin expression in the brain. Here, we characterized the expression of the oxytocin system along the mouse gastrointestinal tract and investigated whether this is influenced by the microbiota.

We assessed oxytocin and receptor (OxtR) expression using qRT-PCR in full-thickness intestinal tissues (stomach to colon) from adult C57Bl/6 mice. To investigate the effect of microbial disruption, RNA was isolated from germfree and antibiotic-treated (1g/L ampicillin and gentamicin, 0.5g/L vancomycin, 0.25g/L imipenem, 2weeks) adult male C57Bl/6 mice. To confirm the physiological relevance of OxtR expression, responses to oxytocin were investigated in mucosal-submucosal preparations under voltage clamp conditions in Ussing chambers.

Oxytocin and OxtR genes were expressed at low levels along the length of the gut. OxtR mRNA expression was higher than oxytocin expression, with the highest expression observed in the stomach and proximal colon. Germfree status did not significantly affect oxytocin expression. In contrast, antibiotic treatment decreased oxytocin and OxtR expression. In Ussing chamber studies, basolateral application of 1μM oxytocin increased short circuit current in the small intestine whereas in the colon, a decrease was observed.

We demonstrated the presence of a functional oxytocin system in the gut and that oxytocin and OxtR expression are sensitive to cues from the gut microbiome.

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Neuroimmune and metabolic mechanisms in Autism; A systematic review and multi-OMICS bioinformatics analysis of protein and metabolite biomarkers.

Zaineb Hamza1,2, Daragh O’Boyle2,3, Kirsten Dowling2,3, Tine Brink Henriksen4, Bodil Hammer Bech5, Richard Anney6, Lorna M. Lopez7, Louise Gallagher8,9,10, Ali Khashan11, Jane A. English2,3 1. School of Medicine, University College Cork, Cork, Ireland 2. Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; 3. INFANT Research Centre, University College Cork, Ireland; 4. Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; 5. Department of Public Health, Aarhus University, Aarhus, Denmark; 6. Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK. 7. Department of Biology, Maynooth University, Maynooth, Co. Kildare 8. Hospital for Sick Children, Toronto, Canada; 9. Centre for Addiction and Mental Health, Toronto, Canada; 10. Department of Psychiatry, University of Toronto, Canada; 11. School of Public Health, University College Cork, Cork, Ireland; Background: Hundreds of studies have investigated potential blood-based biomarkers of Autism, yet, to date, a comprehensive overview and pathway analysis of putative biomarkers is lacking.

Aim: To consolidate the literature, summarise systemic blood-based biomarkers, and perform a multiOMICS bioinformatics analysis of the molecular pathways implicated in Autism.

Methods: Following a pre-registered PRISMA protocol, MEDLINE, EMBASE and Scopus databases were searched, by two reviewers, who independently screened articles. Studies included were cohort or case-control articles published as primary peer-reviewed studies, using Autism Spectrum Disorder (ASD) as the outcome measure. More than 1000 articles were screened, and papers which included subjects with a confirmed clinical diagnosis of ASD (ICD-10, DSM-IV, DSM-V ADOS, ADI-R, CARS or 3DI criteria), and measured protein/metabolite levels in blood were included.

Results: We reviewed 95 proteomics studies and 59 metabolomics studies in individuals with Autism, as well as 8 studies which investigated maternal mid-gestation biomarkers of Autism. Pathway analysis revealed an enrichment of proteins linked to stress response/inflammation, and consistently implicated the IL-17a pathway. Furthermore, the proteomics data pointed to altered Complement and Coagulation Signalling, MAPK Signalling, JAK-STAT Signalling, TNF Signalling, and Cell Adhesion, with converging evidence from both proteomics and metabolomics datasets to implicate altered Arginine-, Glutathione- and Arachidonic Acid- and -Cholesterol metabolism.

Conclusion: This is the first review to consolidate proteomics and metabolomics evidence for systemic immune and metabolic biomarkers in Autism.

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Comprehensive Analysis of Non-Small Cell Lung Cancer Driver Mutations in the Cork/Kerry Region: A 7-Year Retrospective Study.

Dr. Julie Twomey1,2, Dr. Dearbhaile Collins1,2, Prof. Louise Burke2,3 Reiltin Werner2,3, Dr. Collette Hand2,4 1. Department of Medical Oncology, Cork University Hospital.

2. School of Medicine, University College Cork.

3. Department of Pathology, Cork University Hospital.

4. Department of Pathology, School of Medicine, University College Cork.

Introduction: The identification of driver mutations in Non-Small Cell Lung Cancers (NSCLC) has revolutionised cancer treatment through precision oncology. Understanding the regional prevalence of these mutations can aid in optimising treatment pathways for patients. This study aims to characterise the NSCLC mutation landscape in the Cork/Kerry region.

Methods: A retrospective review was conducted on all NSCLC tumour specimens submitted to Cork University Hospital (CUH) for molecular analysis between January 2017 and December 2023. Included were specimens analysed using Next-Generation Sequencing (NGS) at CUH or an off-site referral Laboratory, and those analysed with Single Gene Testing (SGT) for EGFR, ALK, or KRAS gene mutations at CUH. Patient demographics and tumour histopathology data was collected. Data was analysed using SPSS and compared to results of a national study by Keogh et al, 2023.

Results: This study included 737 NSCLC patients, with adenocarcinoma the predominant histopathological subtype (80%). Driver mutations were identified in 50% of patients. KRAS mutations were most frequent (29%) one third of which were the targetable G12C mutation . Less frequent were EGFR (15.8%,), ALK(1.9%) and BRAF (1.9%). While overall prevalence rates were concordant with those seen in the national study, a higher EGFR mutation rate was identified in this study (15.8% vs 8.4%), possibly due to the inclusion of SGT data.

Conclusion: This study presents a comprehensive NSCLC mutation profile for the Cork/Kerry region, providing insight into regional patient characteristics for future clinical decisions, clinical trials and resource allocation.

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Medical Students' Preparedness to Provide Cross-Cultural Care: A Crosssectional Survey Julia Galarowicz1, Dr Aislinn Joy2 1. School of Medicine, UCC 2. Medical Education Unit, School of Medicine, UCC Introduction: Existing literature suggests a deficit in the readiness of medical students to provide crosscultural care, which involves an understanding of the diverse traditions, beliefs and societal norms held by patients of differing backgrounds. With the rise of the non-Irish population and an increase in overseas medical practice, encountering patients of diverse cultures is inevitable. This study aims to assess this domain of the medical student experience.

Aims: To assess UCC medical students’ skillfulness, preparedness and perception of the educational climate regarding cross-cultural care. To investigate the factors that influence UCC medical students’ readiness to provide cross-cultural care.

Methods: Following ethical approval, a validated survey was distributed electronically to all UCC medical students. Responses were collected via Microsoft Forms and the data was analysed using SPSS. Results: From 141 responses, most students felt unprepared for cross-cultural care in 4 out of 8 preparedness items. Students were largely unskillful in 6 out of 10 skillfulness items. There was no association between year of study and preparedness to provide cross-cultural care. 95% of respondents had not encountered cultural training in the medical curriculum, yet 86.4% of students agreed that this type of training should be included in the curriculum. The education climate in UCC relating to cross-cultural care showed to be “a small problem”.

Conclusion: The findings of this study highlight the lack of readiness of UCC medical students to provide care to culturally diverse patients. This study sheds light on current gaps within the medical curriculum regarding cross-cultural training.

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Community Pharmacists’ Views on Extending Prescription Duration in Ireland: A Survey Study Ruth Maher1, Dr Kieran Dalton1, Dr Suzanne McCarthy1 1. School of Pharmacy, UCC Background: Transforming healthcare in Ireland requires innovative approaches, such as pharmacist prescribing, to improve access to care by harnessing pharmacists' expertise, easing GP workload, and delivering timely treatment for common conditions. This evolving role reflects a strategic shift toward a more collaborative and accessible healthcare system in Ireland.

Aim: This study aimed to explore Irish pharmacists’ views on new legislation allowing pharmacists to extend prescriptions from six months to a maximum of 12 months. The goal was to guide the implementation of this and other expanded roles.

Methods: In June 2024, an online survey was distributed to pharmacists in Ireland through the Pharmaceutical Society of Ireland (PSI). The survey gathered pharmacists' perspectives on prescription extension including its potential impact, barriers to implementation, and their confidence in the new role.

Results: A total of 759 pharmacists responded. Of these, 55.5% anticipated that prescription extension would enhance access to care. Pharmacists felt that the strongest barrier to implementation was not having access to patients’ medical records. The outcomes deemed most concerning were patient pressure to extend prescriptions (38.2%), increased risk of litigation (37.7%), appropriate reimbursement (25.3%) and additional workload for pharmacists (24%). Moreover, 31.6% of respondents expressed low confidence in adopting this new role.

Discussion: The survey provides key insights into community pharmacists’ perspectives in Ireland.

These findings should guide the planning and implementation of expanded pharmacist roles to address the rising demand for healthcare and support a multidisciplinary approach to deliver high-quality care into the future.

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Preparedness for dermatology practice from internship - an evaluation of undergraduate medical dermatology education Nicola Kearney1, Aislinn Joy1 1. Medical Education Unit, School of Medicine, UCC Background: Dermatological conditions are the fourth most common of all diseases affecting humans, and affect almost one third of the world’s population,necessitating effective undergraduate dermatology education.

Aims: 1. To enquire about the self-perceived confidence of newly qualified junior doctors in recognising and diagnosing dermatological conditions 2. To ascertain information pertaining to newly qualified junior doctors' undergraduate dermatology education Methods: A mixed-methods survey on undergraduate dermatology education and self-perceived confidence levels of interns in relation to dermatological conditions was distributed to interns working within two Irish intern networks.

Results: Fifty-seven interns completed our survey. A total of 60% of respondents were female (n=34).

The median age range of respondents was 25-29 years. 58% of interns had a clinical dermatology undergraduate placement (n=33). Forty-nine percent of interns were dissatisfied with their undergraduate dermatology education (n=28), while 26% (n=15) were satisfied and 25% (n=14) indicated neutral feelings. Confidence levels reported were reasonable where inflammatory and malignant dermatoses were concerned. Mann-Whitney U testing was used to test for differences between those who had a dermatology placement versus those who did not; statistical significance was established across several areas in dermatology.

Conclusion: This study demonstrates that undergraduate dermatology education is not standardised across various universities in Ireland. It also revealed several areas within dermatology within which there was a statistically significant difference in confidence levels in those who had a clinical undergraduate dermatology placement versus those who did not, suggesting that mandating a dermatology clerkship may be beneficial to interns.

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Bacteria biofilm in a clinical setting: How are dental healthcare professionals in private dental practices combating the formation of biofilm in dental unit waterlines Laura Dunning1, Dr Maura Smiddy1 1. School of Public Health, UCC Aim: The aim of this study is to examine how dental healthcare professional in private dental practices are combating the formation of biofilm in dental unit waterlines.

Methods: A quantitative cross-sectional design. A Google Forms questionnaire was used to collect data from dental professionals (N=61). A WhatApp group was used to source participants. The group of participants were chosen, as they are involved in the daily maintenance and operation of DUWLs in their clinical settings. The data was analysed using descriptive and inferential statistics.

Results: 70% (n=43) of participants said they disinfect their DUWLs, 63% (n=38) flush water lines at the end of each day,. 12% (n=7) of participants did not disinfect nor flush their DUWLs. 41% of participants (n=25) felt adequately informed about biofilm management and infection control measures in dental unit waterlines. 85% of respondents provided the correct response to the knowledge-based questions related to management of DUWL. Two associations were discovered. The first between singledisciplinary and multidisciplinary clinics regarding disinfection status. The water line disinfection between single and multi-discipline clinics. Multidisciplinary clinics were more likely than singlediscipline clinics to disinfect their water lines. The second between practice location and DUWL disinfection status, Munster and Leinster participants more likely to disinfect their DUWLs. Conclusion: Future research could explore dental healthcare workers attitudes and perceptions of DUWL IPC or dental IPC as a whole. However, based on the results addressing the identified gaps in practice and understanding, dental clinics can enhance their IPC measures, thereby improving patient and practitioner safety.

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Dual targeting of BRD4 and CDK12 synergistically induces cell death in breast cancer via suppression of IL6/STAT3 signalling Patrycja Domeracka1, Diarmaid Nagle1, Rosemary O’Connor1, Ken Nally1,2, Malgorzata Krajewska1 1. School of Biochemistry & Cell Biology, Biosciences Institute, UCC 2. APC Microbiome Ireland, UCC Triple-negative breast cancer (TNBC) poses a significant challenge in oncology due to its limited therapeutic options. Thus, innovative treatment strategies are needed to improve outcomes for TNBC patients. Cyclin-dependent kinases (CDKs) regulating transcription, such as CDK12, have been recognized as potential therapeutic targets in cancer. Our studies and others demonstrated the anticancer efficacy of CDK12 inhibition in various cancers, including TNBC. However, the development of resistance to monotherapy is inevitable. Here, using in silico analysis, we identified BRD4, a bromodomain-containing protein involved in transcription and epigenetic regulation, as a potential candidate for combination therapy. We discovered that co-targeting CDK12 and BRD4 synergistically induced DNA damage and caspase-dependent apoptosis in TNBC cells compared to the single-agent treatment. Interestingly, RNA sequencing analysis revealed significant downregulation of genes associated with inflammation and STAT3 signalling following the combination treatment. Integrated gene function and network analysis further highlighted interleukin 6 (IL-6), a key pro-inflammatory cytokine, as a plausible mediator of transcriptional changes induced with the combination.

Mechanistically, CDK12 inhibition increased IL-6 secretion by TNBC cells while co-targeting CDK12 and BRD4 diminished IL-6 levels and suppressed STAT3 activity, indicating an IL-6-dependent effect on STAT3 signalling. Additionally, combined targeting of CDK12 and BRD4 downregulated epidermal growth factor receptor (EGFR) expression and blocked downstream AKT and ERK signalling, further enhancing the anti-cancer effects in TNBC cells. This study uncovers a novel combination of CDK12 and BRD4 inhibition as a promising therapeutic strategy in TNBC, disrupting key oncogenic pathways and likely delaying the development of resistance to CDK12 inhibition.

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The co-production of oral health promotion infographics for children and young people with Type 1 diabetes mellitus (T1D), their families and health professionals Mairead A. Harding1,2, Shirley Beattie3, Irene O'Mahony3, Annelise Hutch3, Colin Hawkes4,5, Rose Kingston1,2, Julia Banasiak2,6, Maria Tobin2 1. Cork University Dental School and Hospital 2. Oral Health Services Research Centre 3. Department Nutrition and Dietetics, Cork University Hospital 4. Department of Paediatrics and Child Health, UCC 5. INFANT Research Centre, UCC 6. School of Public Health, UCC Background: In Ireland the incidence of type1 diabetes mellitus (T1D) in children and young people (CYP) is high. In addition, there is an association between poorer oral health outcomes for CYP with T1D. Awareness of this association amongst health professionals, families and CYP living with T1D is low.

Objective: To build collaborative engagement amongst health professionals and families living with T1D in CYP and with facilitated engagement identify key oral health messages for dissemination.

Methods: Through networking and PPI engagement, groups with experience of T1D in CYP were convened, involving health professionals, student health professionals and families with lived experience. Through facilitation key oral health messages, challenges in adopting evidence-based practices and the knowledge gaps were explored and progressed. Through collaboration key information content was agreed along with methods of information dissemination.

Results: A4 size infographics for children ≤12-years, children ≥12-years and parents/carers were designed. Paper and digital formats were created, and all linked via QR codes. Suitable colour schemes, graphics, font size, language and reading level were approved.

Agreed oral health messages: • Age-appropriate toothbrushing instructions.

• After toothbrushing spit out toothpaste • Use a straw with sugar containing and carbonated drinks.

• Instructions for flossing, mouthrinse use and for braces • Do not smoke • Regular dental check-ups Conclusion: Knowledge is poor about the association between oral health outcomes for CYP with T1D amongst relevant personnel and families. To close this knowledge gap collaboration amongst health professionals, and affected families is critical for knowledge improvement and information dissemination.

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Listening in. Ultrasonic vocalisations in rats exposed to gram-positive bacterial proteins.

Anna O'Connell1,2, Fiona McDonald1,2 1. Department of Physiology, School of Medicine, College of Medicine and Health, UCC 2. INFANT Research Centre, UCC Ultrasonic vocalisations (USVs, >20 kHz) provide a mechanism for a rodent pup to communicate with its mother for self-preservation and retrieval. Ultrasonic vocalisations emitted from the rat have been used as an index of stress. Previous data from our lab revealed an increase in circulating cytokines and cortisol following administration of immune stimulants. In this study, we sought to examine if exposure to gram-positive bacterial proteins altered ultrasonic vocalisations of acutely isolated male and female rats. The project was ethically approved by AEEC, UCC and HPRA, Ireland. Ultrasonic vocalisations were recorded non-invasively using ultravox microphone and recording system and analysed using DeepSqueak open software. On postnatal day 13 male and female Sprague Dawley rat pups were removed from their home cage and placed in an insulated box. USVs were recorded for 5 minutes (n=10-11 per group). Immediately after animals were given i.p injection of saline or immune stimulants (lipoteichoic acid (LTA) & peptidoglycan (PGN)) and placed back into their home cage. Three hours later ultrasonic vocalisations were again recorded (10minutes). We report that administration of LTA and PGN i.p did not alter the number of calls (Two-way ANOVA injectable p=0.2) and there was no statistical difference in the number of calls between males or females (p=0.06). Further analysis will examine the frequency and duration of the calls made. The frequency of USVs have been associated with either positive affect (high frequency) or negative affect (lower frequency) in rats. Further analysis will give further insight to the behavioural response to acute inflammation.

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Examining the physiology of the gastrointestinal tract in an animal model of neonatal oxygen dysregulation.

Carla Viñola-Renart1,2,3*, Anna O’Connell1*, Friederike Uhlig2,3#, Fiona B McDonald1# (* joint first authors, # joint senior authors) 1. Department of Physiology, School of Medicine, College of Medicine and Health, UCC 2. Department of Anatomy and Neuroscience, School of Medicine, College of Medicine and Health, UCC 3. APC Microbiome Ireland, UCC During early life the intestinal system develops rapidly, and proper functioning of the gastrointestinal tract is important for homeostasis. We investigated if early life oxygen dysregulation and subsequent immune activation changes intestinal barrier function.

Ethical approval was granted by AEEC and HPRA. Sprague Dawley rat pups were exposed to changing FiO2 (8%, 21%, 30%) (CIHH) or housed at room air (sham), 24 hours/day for 10 days (postnatal day (PND) 3-12). On PND 13 animals were given saline or immune stimulant (lipoteichoic acid & peptidoglycan, LTA/PGA) i.p. Four hours later, rat pups were euthanised by isoflurane and cervical dislocation and the intestine removed. Seromuscular stripping was performed in ice-cold physiological Krebs solution under the stereomicroscope. Mucosa-submucosa preparations of the ileum (3 cm proximal to the ileocaecal junction) were mounted in Ussing chambers. Baseline parameters (short circuit current, ISC and transepithelial electrical resistance, TEER) as well as responses to secretory stimuli Carbachol (100 μM) and Forskolin (10 μM) were examined.

Preliminary analysis revealed that small intestinal ISC was unaffected by either CIHH or LTA/PGA. TEER was significantly lower in CIHH group compared to Sham group (2-way ANOVA, p = 0.019, n=3-6) suggesting increased permeability, whereas LTA/PGA treatment had no effect (2-way ANOVA, p > 0.05).

Secretory responses to Carbachol and Forskolin tended be increased in CIHH animals (2-way ANOVA, p = 0.12 for Carbachol and p = 0.14 for Forskolin).

Our preliminary findings suggest oxygen dysregulation but not acute immune activation in early life impairs gastrointestinal function, further assessments will be performed

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Learning Outcomes for Interprofessional Medication Safety in Undergraduate Health Education.

Ellen Blackburne1, Aisling Joy2 1. School of Medicine, UCC 2. Medical Education Unit, School of Medicine, UCC Introduction: Cohesive interprofessional working between healthcare professionals is a fundamental principle in safe medication provision. In order to achieve this safe collaborative workplace dynamic, education is required at an undergraduate level. However, a recent scoping review has revealed a gap in the reporting of interprofessional medication safety learning outcomes.

Aims: This study focuses on the usefulness of undergraduate, medication safety (MS)-related interprofessional education (IPE), by evaluating senior cycle medical and pharmacy students’ selfreported learning outcomes, professional development, and attitudes towards teamwork and satisfaction, following an IPE intervention.

Methods: A mixed methods questionnaire was designed to evaluate learning outcomes from the MSrelated IPE, via Likert Scale and Open questions. Following ethical approval, final year medical and pharmacy students were invited to respond to questionnaire via email and UCC MSForms, once they had participated in a ward-based interprofessional medication safety workshop. Both qualitative (content analysis) and quantitative (via SPSS) methods were used in the analysis of findings.

Results: 52 students responded to this questionnaire. Following the IPE medication safety workshop, 73% agreed that they are on the path to becoming a good and safe prescriber, with 96.1% agreeing that they are able to appropriately engage with other health professionals in shared problem solving.

100% of respondents agreed that they would place the interests of patients at the centre of interprofessional health care delivery.

Conclusion: The results of this study reinforce the postulation that MS-related IPE is informative, beneficial and worthwhile for students. This highlights the importance of MS-related IPE as part of the curriculum for undergraduate students, in order to improve confidence and ability to use medication safely, as well as to reduce medication harm.

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Poster Numbers and Room Locations Room Number

Poster Presenting Author(s) Number

WGB_G15

1

Julie Arnott

WGB_G15

2

Aisling Jennings

WGB_G15

3

Kate O'Connell

WGB_G15

4

Kate O'Connell

WGB_G15 WGB_G15 WGB_G15

5 6 7

Sasna Saji Thomas Andrew Octavian Sasmita James O'Flynn

WGB_G15

8

Aisling Maher

WGB_G15

9

Pauline Frizelle

WGB_G15

10

Pauline Frizelle

WGB_G15

11

Pauline Frizelle

WGB_G15

12

Dr. Katja Burk

WGB_G15

13

Dr. Anne-Marie Martin

WGB_G15

14

Maria Kulecka

Abstract Title Can Artificial Intelligence (AI) be responsibly harnessed to increase public health literacy and trust in our national health information website? A feasibility assessment for implementing policy into practice Stakeholder perceptions of and attitudes towards problematic polypharmacy and prescribing cascades: a qualitative study Evaluation of a Complex Survivorship Intervention incorporating Electronic Patient -Reported Outcomes in Early-Stage Breast and Gynaecologic Cancer: Results from the Linking You to Support and Advice (LYSA) Randomised Control Trial (RCT) The Practice Changing Linking You to Support and Advice [LYSA] Randomised Control Trial: A Patient-Guided Multidisciplinary Survivorship Trial THE VOICES ARE BEING HEARD: THE UCC CTG PPI INITIATIVES IN CANCER RESEARCH Dysfunctional myelin worsens phosphorylated tau-induced pathologies in a mouse model of tauopathy An Investigation into General Practitioners’ experience with Long Covid Assessing the Impact of a Tailored Educational Intervention to Improve Clinical Communication involving Adults with Age-Related Hearing Loss How reliable is assessment of children’s sentence comprehension using a self-directed app? A comparison of supported versus independent use.

The understanding of complex syntax in children from 5 – 9 years, using a novel assessment approach - the Test of Complex Syntax- Electronic (TECS-E) The co-construction of a reading assessment checklist with adults with Down syndrome: a meaningful literacy approach.

ATXN2 intermediate expansions in Amyotrophic Lateral Sclerosis affect neurofilament regulation and reveal new patterns in pathogenic markers THE-DIET: Facilitators' experiences of delivering a tailored health education resource to people with mild/moderate intellectual disability.

Microbiome-related biomarkers for relapse prediction in treatment-naïve paediatric ulcerative colitis patients

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Room Number

Poster Presenting Author(s) Number

Abstract Title Prescribing cascades among older community-dwelling adults in Ireland: prescription sequence symmetry analysis of ThinkCascades in a national dispensed prescription database.

Oral care for post-stroke in-patients with dysphagia – a systematic review Breastfeeding and parental cardiometabolic risk: a prospective cohort study comparing maternal and paternal associations in mid-life A systematic review and meta-analysis of the effectiveness of social prescribing in the management of longterm conditions Using wearable devices and AI to track the migraine cycle Harnessing AI and Wearables for Personalized Mental Health Interventions Wearable wireless system for electrochemical measurements using laser-induced graphene sensors.

Role of the Gestational Maternal Gut-Microbiota in the Neurodevelopment of the Hypothalamus and the Amygdala Building Social Capital - Essential and Desirable Characteristics for the Successful Large-Scale Implementation of a Targeted Selective Speech, Language and Communication Intervention Programme for Children Living in Social Disadvantage Caesarean Section and Risk of Psychiatric Disorders in Offspring during Adolescence and Adulthood: A Systematic Review and Meta-Analysis Collecting Information in Child Health Research Studies Factors influencing use and choice of Core Outcome Sets and Core Outcome Measurement Sets in trials of interventions to prevent childhood obesity.

WGB_G15

15

Dr Ann Doherty

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16

Claire Curtin

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17

Farzana Ferdous

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18

Declan O Sullivan

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19 20 21

Salvatore Tedesco Salvatore Tedesco Marco Sica

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22

Lorena Morales García

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23

Esther Ivy Atuhaire

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24

Moira Duffy

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25

Moira Duffy

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26

Eibhlín Looney

WGB_G15

27

Vuslat Juska

Translational Chemistry and Microtechnologies for Biomedicine: Advancing the Alzheimer Disease Diagnostics through Molecular Pendulum

WGB_G15

28

Clíodhna Nolan

Advancing biobanking and sample utilization in blood cancer research: A report from the Blood Cancer Network Ireland (BCNI) Biobank, Cork.

WGB_G15

29

Mariarosaria Cuozzo

Lactobacillus rhamnosus Soluble Mediators Improve Cell Viability and Display Anti-inflammatory Properties on LPS-Induced Inflammation of VK2 Cells

WGB_G15

30

Dr Samantha Cushen

WGB_G15

31

Stephanie Corkery

Exploring the Impact of a Dietetic Intervention on Body Composition in Breast and Gynaecologic Cancer Survivors: Results from the Linking You to Support and Advice [ LYSA] Randomised Control Trial Body Composition in Males Impacted by Metastatic Genitourinary Cancer: Results from the Pilot Component of the LIAM Mc Trial.

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Poster Presenting Author(s) Number

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32

Karen Matvienko-Sikar

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33

Emilene Morais

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34

Rachel Linehan

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35

Prachi Sharma

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36

Prachi Sharma

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37

Maura Hannon

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38

Barbara Collins

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39

Mairéad O'Donnell

WGB_G15

40

Ciarán Devoy

WGB_G15

41

Karen Molan

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42 43

Ciaran Lee Dr Helen Kelly

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44

Michael Prentice

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45

WGB_G15

46

Peter Doyle Friederike Uhlig and Alice Kellaghan

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47

Friederike Uhlig

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48

Mairead Harding

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49

Niall O'Reilly

Abstract Title What and how we measure outcomes in health research matters: The example of childhood obesity prevention Prospective Evaluation of the Breast Microbiome and Tumour Microenvironment-related Biomarkers of Response to Neoadjuvant Systemic Therapy in Triple Negative Breast Cancer Safe Staffing: The Pilot Testing of the RUG-IV Instrument in Ireland.

Sex-specific socioeconomic inequalities in physical activity trajectories from late childhood to early adulthood: a prospective cohort study Patterns of Sex-specific Socio-economic inequalities in e-cigarettes, traditional cigarettes and dual use among young adults: a prospective descriptive study.

Crying out over spilt milk: Quantifying formula milk waste in a large maternity hospital Investigating Mechanistic PRedictors Of interpatient Variability and temozolomide (TMZ) induced haematological toxicity for glioma patients. (IMPROVE TMZ) Understanding COPD mortality in Cork University Hospital 2022-2023. HIPE vs Reality.

A study within a study: Logistics of patient sample acquisition in academic clinical microbiome studies: Identification of determinant factors of success.

A quality improvement project to enhance implementing regulatory protocol amendments in a radiotherapy clinical trials department at the Bon Secours Radiotherapy Centre Cork in partnership with UPMC Hilman Cancer Centre.

Genetic Therapies for Rare Disease Consulting Marginalised Communities and Minority Groups to inform a National Inclusion Health Framework Insights from Analysis of Uropathogenic Escherichia coli Whole Genome Sequences from Cork University Hospital Introducing A New Treatment Protocol to CUH: An Audit of the Practical Experience Investigating the potential of whey proteins as a treatment for modulation of appetite using FED3.1 devices Characterization of Oxytocin Gene Expression in the Mouse Gastrointestinal Tract and Sensitivity to Microbial Disruption The co-production of oral health promotion infographics for children and young people with Type 1 diabetes mellitus (T1D), their families and health professionals The Ukrainian Experience of General Practice in Ireland

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Room Number

Poster Presenting Author(s) Number

Abstract Title Long term clinical outcomes in sustained dose reduction strategies for elexacaftor/tezacaftor/ivacaftor (ETI) – indications and outcomes: a case series Comprehensive Analysis of Non-Small Cell Lung Cancer Driver Mutations in the Cork/Kerry Region: A 7-Year Retrospective Study.

From Design to Dissemination: The Value of PPI in the LYSA Clinical Trial Factors Influencing Medication Adherence Among People With Anxiety Or Depression: A Cross-Sectional Study Using Data From The Mitchelstown Cohort Rescreen Study 2015 Fluctuations in Parkinson's disease symptoms and effectiveness of medications over the menstrual cycle.

Irish College of General Practitioners’ (ICGP) trainee experiences following transition from hospital to general practice: a qualitative study.

WGB_G15

50

Noreen Tangney

WGB_G15

51

Dr. Julie Twomey

WGB_G15

52

Katarina Medved

WGB_G15

53

Louise Hearne

WGB_G15

54

Sarah Moore

WGB_G15

55

Fodhla Ni Dhalaigh

WGB_G15

56

Lauren Barrett

SKOR1 as a potential therapeutic target in preventing α-synuclein-induced degeneration in models of Parkinson’s disease.

WGB_G15

57

Sophia V. Hoffmann

Influence of Capsule Size on Gastric Emptying of Enteric Capsugel® Enprotect® Capsules in Pigs

WGB_G15

58

Qingyue Wang

WGB_G13

59

Brenda Au

WGB_G13 WGB_G13

60 61

Klara Martinović Mušić Darren Crowley

WGB_G13

62

Reiltin Werner

WGB_G13

63

Reiltin Werner

A clustering-based methodology for cell-type deconvolution in spatial transcriptomic analysis A Negative Experience: Exploring the Perspectives of Healthcare Assistants on Pain Management at End-ofLife for People Living with Dementia in a Nursing Home Evaluating Adrenomedullin as a Target of Oral RNA-based Therapy for Ileal Crohn’s Disease Factors that Predispose Glioma Patients to Haematological Toxicity with Temozolomide: A Scoping Review The Idylla™ IDH1-2 Mutation Assay Kit demonstrates high sensitivity and specificity for detection of IDH mutational status in glioma.

Implementation of an ISO 15189 Accredited Next Generation Sequencing (NGS) Service for Cell-Free Total Nucleic Acid (cfTNA) Analysis to Facilitate Driver Mutation Reporting in Plasma.

WGB_G13

64

Susan Burke

Investigation of the impact of experimental Traumatic Brain Injury on acute changes in immuno-metabolism gene expression in the mouse cortex and hippocampus.

WGB_G13

65

Sabrina Alom

PEGDM and nHA-PEGDM Hydrogels for Biomedical Applications

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66

Rachel Roberts

Exploring the Impact of LRRK2 Genetic Mutations on Cellular Susceptibility to Pesticides as a Risk Factor for Parkinson’s Disease

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Abstract Title Exposure to serum from biologically stressed pregnant women decreases neurite length in SH-SY5Y cells through a tumour necrosis factor-α-dependent mechanism The Maternal Gut Microbiota Modulates Neurodevelopment Through Regulation of The Blood-Cerebrospinal Fluid Barrier Permeability.

WGB_G13

67

Clara Deady

WGB_G13

68

Jennifer Morael

WGB_G13

69

Sonia Akther and Sheesa Joseph

Pharmacist Roles In Delivering Cardiac Rehabilitation: A Scoping Review Of The International Literature

WGB_G13

70

Emma Crowley and Leah Casey

Comparing Compliance Levels of Regular and “As Required” Prescription Orders in an Irish Teaching Hospital : A Clinical Audit

WGB_G13

71

Sarah Ni Mhaolcatha

Death Investigation and Certification During the COVID-19 Pandemic in Ireland: Retrospective Review to Inform Responses to Future Pandemics

WGB_G13

72

Aisling McDonald

WGB_G13

73

Mahi Bhandarkar

WGB_G13

74

Majella Bradley

WGB_G13

75

Jolie Morisho

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76

Áine Jennifer Gorman

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77 78 79 80

Francisca Soares Patrice Crowley Yue Wu Hugo Blair

WGB_G13

81

Jill Mitchell

WGB_G13

82

Alexandre J.C. Cergneux

An audit examining the compliance of ‘as required’ prescription orders to hospital prescribing standards for adult inpatients of an Irish teaching hospital.

A patient satisfaction survey for a movement disorder clinic at St. Finbarr's Impact of Staff Turnover on Implementation of Infection Prevention and Control in Nursing Homes.

Staff turnover in significantly impacts effective implementation of infection prevention and control measures.

This systematic review aimed investigated the relationship between staff turnover and IPC effectiveness in nursing homes identifying key challenges and strategies for improvement.

The overexpression of human wild-type alpha-synuclein impairs GDNF-mediated activation of Akt and ribosomal protein S6.

A Cost-Effectiveness Analysis of a Community-Based Wheelchair Skills Training Intervention for Individuals with Neuro-physical Disabilities.

Cyclodextrins-Based Nanoparticles For Intestinal Delivery of RNA Identifying unmet palliative care needs of nursing home residents: A scoping review Prevalence and factors associated with depression and depressive symptoms: an integrative review The Maternal Gut Microbiota Regulates Embryonic Cortical Development in Mice Association between Intrapartum Fetal Pulse Oximetry and Adverse Perinatal and Long-term Outcomes: a Systematic Review and Meta-analysis Maternal Microbiome-Mediated Effects on Offspring Neurovascular Development Page | 149

Room Number

Poster Presenting Author(s) Number

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83

Anthony James Goodings

WGB_G13

84

Laura-Jane McCarthy

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85

Chelsea Nwankwo

WGB_G13

86

Ashley Benge

WGB_G13

87

Nerea Hernández Egido

WGB_G13

88

Omar Sabra

WGB_G13

89

Patricia Margaret Flynn

WGB_G13

90

Fionnuala Wilson

WGB_G13

91

Amy Walsh

WGB_G13

92

Qiao Xiao

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93

Amiee Cronin

WGB_G13

94

Cristina Cuesta-Marti

WGB_G13

95

Aman Saifi

WGB_G13

96

Hisham Ibrahim

WGB_G13

97

Hisham Ibrahim

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98 99

Meaghan Richardson Clíona O'Connor

Abstract Title Inhaler Usage and Environmental Impact. An Irish Perspective on knowledge, attitudes and environmentally friendlier prescription practices.

General Practitioners’ and women’s experiences of perimenopause consultations: a qualitative evidence synthesis Barriers and Enablers to Attendance at Structured Diabetes Education Programmes: A Systematic Review Cadaveric Case Study of Vertebral Artery Coiling at the C3 Level: Anatomical Variability, Morphometric analysis and Clinical Implications Engineering circular RNAs for selective protein expression in dysfunctional endothelial cells for the treatment of sepsis.

Developing Human Milk Oligosaccharides as Novel Polysaccharides for Microbiota-Triggered Release from Film-Coated Pellets Retinoid specificity in mediating growth suppression in glioblastoma stem cells Examining the therapeutic potential of AAV-GDF5 and AAV-GDNF in an α-synuclein rat model of Parkinson’s disease Expanded Vδ1 γδ T cells from healthy donor PBMCs display a cytotoxic phenotype with cytotoxicity elicited against colorectal cancer cells.

Luminal Lithocholic acid can modify colonic secretory function via basolateral secretion of interleukin-6.

Investigation of the impacts of maternal prebiotic supplementation on anxiety and depression-like behaviours during postpartum and early life stress in female mice.

Shaping Healthy Eating: Priming healthy eating behaviour from early life to adulthood in mice using microbiota-targeted interventions Targeted delivery of RNA-based therapeutics to the gut to modulate the JAK-STAT pathway in Crohn’s Disease Added Benefit of Triple Therapy for Cystic Fibrosis Patients with Phe508del–Gating Genotype: A Real-world Prospective Study.

Long-term real-world outcomes of CFTR modulation with Ivacaftor in adult cystic fibrosis patients with the G551D mutation; 8 years single center real-world study.

Developing non-coding synthetic circular RNA tools for modulation of gene and protein expression in sepsis Investigating L cells as cross-barrier signal transducers of microbiota-gut-brain communication

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Poster Presenting Author(s) Number 100 Ciara Gavin 101 Ellen Power

WGB_G13

102

Kevin Deasy

WGB_G13

103

Paul Ryan

WGB_G13

104

Neve Gavin

WGB_G13

105

Ruth Daunt

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106 107

Méabh Finucane Robert Callaghan

WGB_G13

108

Zaineb Hamza

WGB_G13 WGB_G13

109 110

Julia Galarowicz Ruth Maher

WGB_G13

111

Nicola Kearney

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112

Laura Dunning

WGB_G13

113

Patrycja Domeracka

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114 115 116

Anna O'Connell Carla Viñola-Renart Ellen Blackburne

Abstract Title The role of voltage-gated calcium channels in oesophageal adenocarcinoma Identifying potential synergistic effects of retinoic acid and kinase inhibitors in glioblastoma cells Exploring different sampling techniques to best characterise the airway microbiota in people with CF (pwCF) on ETI (elexacaftor/tezacaftor/ivacaftor) with prior P. aeruginosa (PA) colonisation How are direct healthcare professional communications (DHPC) operationalised by General Practitioners (GPs) and community pharmacists in Ireland?

Medical Students’ Perspectives on Oncology in the Undergraduate Curriculum: a Cross-Sectional Study An Investigation into Factors Influencing Recognition of Prescribing Cascades Amongst Medical Hospital Doctors.

Microbial metabolites suppress the tumour promoting functions of IL-36 cytokines in colorectal cancer Behavioural Assessment of Neuropsychiatric Outcomes in Rodent Stroke Models: A Systematised review Neuroimmune and metabolic mechanisms in Autism; A systematic review and multi-OMICS bioinformatics analysis of protein and metabolite biomarkers.

Medical Students' Preparedness to Provide Cross-Cultural Care: A Cross-sectional Survey Community Pharmacists’ Views on Extending Prescription Duration in Ireland: A Survey Study Preparedness for dermatology practice from internship - an evaluation of undergraduate medical dermatology education “Bacteria biofilm in a clinical setting: How are dental healthcare professionals in private dental practices combating the formation of biofilm in dental unit waterlines?”

Dual targeting of BRD4 and CDK12 synergistically induces cell death in breast cancer via suppression of IL6/STAT3 signalling Listening in. Ultrasonic vocalisations in rats exposed to gram-positive bacterial proteins.

Examining the physiology of the gastrointestinal tract in an animal model of neonatal oxygen dysregulation.

Learning Outcomes for Interprofessional Medication Safety in Undergraduate Healthcare Education

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