Student Summer Research Awards – SSRA Abstracts of the SSRA September 2023 meeting, UCD School of Medicine

ENHANCING INTEGRATED CARE: EVALUATION OF A PBRN USING THE IMPLEMENTATION RESEARCH MODEL (IRLM)

Lee O¹, Broughan J¹, McCombe G¹, Cullen W¹

¹UCD School of Medicine, University College Dublin, Ireland

A practice-based research network (PBRN) is a group of practices that draws on clinician insight to identify research gaps and address relevant primary care issues. In 2020, the UCD / Ireland East Hospital Group (IEHG) established its own PBRN, the General Practice Research Network (NETWORK), which aimed to promote care integration, specifically between primary and secondary care. While evaluating PBRNs’ has historically been challenging (1), frameworks to address this have recently emerged, for example, the Implementation Research Logic Model (IRLM) (2). We aimed to evaluate the performance of NETWORK using the IRLM.

The IRLM consists of four interrelated elements namely determinants, implementation strategies, mechanisms, and outcomes. We retrospectively evaluated each element and their relations using previously collected data from NETWORK research projects (i.e., scoping reviews, mixed-method studies, practice recruitment data). The projects which this data was extracted from examined initiatives to reduce hospital readmissions among GP patients, enhance GP Long-Covid management, optimise the quality of atrial fibrillation GP care, and enhance GP access to diagnostic imaging.

The results of the IRLM evaluation characterised determinants as facilitators or barriers to optimal NETWORK performance. These included the NETWORK’s focus on research examining priority health policy issues and limited member-GP time constraints. As for outcomes, we found that the NETWORK achieved good levels of acceptability, appropriateness, feasibility, fidelity, and patient-centeredness.

Outcomes that were not achieved were also identified to signpost the trajectory of future NETWORK development and evaluations, including evaluations examining stakeholder perspectives on their NETWORK experiences to date.

References:

• 1. Bleeker JM, Stalman WA, van der Horst HE. Evaluating primary care research networks: a review of currently available tools. J Am Board Fam Med. 2010;23(4):465–75.

• 2. Smith JD, Li DH, Rafferty MR. The Implementation Research Logic Model: a method for planning, executing, reporting, and synthesizing implementation projects. Implement Sci. 2020;15(1):84.

Presenting Author: Lee Onn

Supervisor: Prof Walter Cullen

Co-Supervisor: Mr John Broughan

HOW CAN BIG DATA BE USED TO MEASURE MENTAL HEALTH AND SUBSTANCE ABUSE DISORDERS IN PRIMARY CARE: A SCOPING REVIEW

Poornaselvan J¹, Broughan J¹

¹UCD School of Medicine, University College Dublin, Ireland

Understanding the rates of mental health issues and assessing their prevalence on a global scale is crucial for effective healthcare planning, resource allocation, and the development of evidence-based interventions. To address and reduce mental health issues within primary healthcare systems, there needs to be an enhancement of analysis of factors and rates for substance abuse and mental health issues within deprived areas. The purpose of this scoping review is to use the big data collected from these studies to apply within the primary care setting to facilitate improved measurements of mental health issues and address the current gaps within deprived communities.

To understand how mental health rates were measured within primary care, a scoping review of the current literature was conducted using the six-stage framework described by Arksey and O’Malley (2005) to gather existing literature, identify key findings and outline current research gaps in this area. The electronic databases used in the searches were ‘PubMed’ and’endnote’. The mesh terms conducted in the search were, “social determinants of health”, “mental health”, “depression”, “wearable technologies”, mental health measurement, “mental health referrals”, and” mental healthcare utilization”.

Current findings include the current rates of mental health utilization within Ireland and the following recommendations.

The use of wearable technology can be used to measure and monitor mental health and the implementation of this can reduce strain within psychiatric clinics and can alleviate referral rates if conducted in primary care. The rates of mental health disorders vary based on socioeconomic needs.

Presenting Author: Jeisun Poornaselvan

Supervisor: Dr Geoff McCombe

EFFECT OF REDUCTIONS IN BLOOD PRESSURE, HBA1C, AND LIPIDS ON CLINICAL OUTCOMES: A SCOPING REVIEW

Chinzorig Y¹, Broughan J³, McErlean S¹, Ryan C⁴, McCombe G¹, Cullen W¹, Gallagher J¹

¹UCD School of Medicine, University College Dublin, Ireland

³Clinical Research Centre, UCD School of Medicine, University College Dublin, Ireland

⁴Beaumont Hospital, Beaumont, Dublin, Ireland

The burdens of cardiovascular disease pose a significant global challenge as around eighteen million people pass away each year. Having uncontrolled CVD risk factors, namely blood pressure, lipids, and A1c can significantly increase a patient's risk of developing life-threatening complications such as atherosclerosis, stroke, and heart failure. [1] This scoping review aims to address gaps in existing literature regarding the interplay between the risk factors, analyze their health impacts on different demographics, and analyze the most effective clinical strategies for enhancing cardiovascular health outcomes.

This scoping review followed Arksey and O'Malley's scoping review guidelines: (a) identifying the research question, (b) identifying relevant studies, (c) study selection, (d) reporting results, and (e) consulting with expert stakeholders. Four electronic databases ("PubMed," "Scopus," "Web of Science," "Cochrane Central Register of Controlled Trials," and "MEDLINE") were used for literature search. The search process was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses - Extension for Scoping Reviews (PRISMA-ScR).

The studies indicate that regulating all three risk factors yields optimal results while monitoring cholesterol and blood pressure should be prioritized due to their crucial roles in cardiovascular health. However, elevated levels of A1c were shown to exacerbate other risk factors [2]. Disparities based on gender, age, and race were observed, supporting individualized treatments tailored to different demographics, potentially more aggressive if necessary.

Healthcare professionals are advised to stay updated on latest research for treatment protocols for CVD while implementing early detection, targeted interventions, and personalized management in clinical settings to optimize health outcomes.

References:

• 1. Cardiovascular diseases (CVDs). World Health Organization, 2021.

• 2. Nichols, G.A., Independent Contribution of A1C, Systolic Blood Pressure, and LDL Cholesterol Control to Risk of Cardiovascular Disease Hospitalizations in Type 2 Diabetes: An Observational Cohort Study. Journal of General Internal Medicine 2013.

Presenting Author: Yanjinbud Chinzorig

Supervisor: Dr Geoff McCombe

PREVALENCE OF MENTAL HEALTH DISORDERS IN GENERAL PRACTICE: A LITERATURE REVIEW

Dillon E¹, McCombe G¹, Sietins E¹, Broughan J¹, Cullen W¹

¹UCD School of Medicine, University College Dublin, Ireland

Mental health is an important aspect of our general health and well-being. General practice is usually the first point of medical contact for patients with mental health problems and the first place where a mental health condition is diagnosed. Therefore it is necessary to obtain information on the prevalence of mental health disorders in general practice to ensure appropriate resources are available for treatment. The purpose of the paper is to provide an updated review of a 2014 review on the prevalence of mental health disorders by Klimas et al. (1).

An extensive literature search was carried out across various electronic databases (PubMed, PsycINFO and google scholar) to identify and analyze studies examining the prevalence of mental health disorders in general practice. Articles were screened using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Overall, prevalence of mental health disorders in patients attending general practice was relatively high (16–37%). The impact of Covid-19 resulted in decreased prevalence towards the beginning of the pandemic due to lower attendance at general practices. (2) Female gender and increased age were associated with a higher prevalence of mental health disorders. Variation in prevalence also occurred across several different countries.

Awareness of the prevalence of common mental health conditions can enhance treatment interventions and mental health outcomes for patients. If we can identify the areas where the burden of mental disorders is particularly onerous, we can aim to alleviate these problems through the targeting of resources in these specific areas.

References:

• 1. Klimas J, Neary A, McNicholas C, Meagher D, Cullen W. The prevalence of common mental and substance use disorders in general practice: a literature review and discussion paper. Mental Health and Substance Use. 2014;7(4):497–508.

• 2. Ahmed N, Barnett P, Greenburgh A, Pemovska T, Stefanidou T, Lyons N, et al. Mental health in Europe during the COVID-19 pandemic: a systematic review. The Lancet Psychiatry. 2023;10(7):537–56.

Presenting Author: Emily Dillon

Supervisor: Dr Geoff McCombe

NATURE-BASED SOLUTIONS FOR MENTAL HEALTH AMONG PATIENTS ATTENDING PRIMARY CARE: A NARRATIVE REVIEW

Yacoob J¹, McCombe G¹, Broughan J¹, Cullen W¹

¹UCD School of Medicine, University College Dublin, Ireland

Nature-Based Solutions (NBS) is an emerging transdisciplinary concept that is defined using natural elements and the environment to benefit health. NBS involves patient exposure to nature which can be achieved by various nature interventions/ therapies through social prescription in the context of primary care. In recent years, NBS have been known to have positive impacts on both physiological and psychological health. This literature review aims to summarise the potential benefits of NBS on psychological health among patients in primary care settings.

A literature review was performed across various databases including PubMed, Google Scholar, PsycInfo and Cochrane library, to identify and analyse the potential benefits of various NBS on psychological health among patients attending primary care. Articles were subsequently screened using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and were reviewed to include various nature-based interventions and its relevant impact on psychological health. The findings were then tabulated and summarized accordingly.

As NBS is an emerging concept in healthcare, a limited number of studies (n = 6) were found in the context of primary care, in the relevant databases. The identified studies indicated that NBS showed improvements among patients in various aspects of psychological health including depression, anxiety, mental wellbeing, social connectedness, and other cognitive benefits[1,2].

Studies found consistent improvements in various aspects of psychological health among primary care patients being exposed to NBS. However, some studies had small sample sizes and increased risk of bias, therefore, more large-scale studies are warranted to fully elucidate the benefits of NBS as it currently shows promising potential in the context of primary care.

References:

• 1. Taylor, E. M., Robertson, N., Lightfoot, C. J., Smith, A. C., & Jones, C. R. (2022). Nature-Based Interventions for Psychological Wellbeing in Long-Term Conditions: A Systematic Review. International Journal of Environmental Research and Public Health, 19(6), 3214.

• 2. Trøstrup, C. H., Christiansen, A. B., Stølen, K. S., Nielsen, P. K., & Stelter, R. (2019). The effect of nature exposure on the mental health of patients: a systematic review. Quality of Life Research, 28(7), 1695–1703.

Presenting Author: Javed Yacoob

Supervisor: Prof Walter Cullen

Co-Supervisor: Dr Geoff McCombe

CHARACTERISATION OF EXTRACELLULAR VESICLES (EVs) FROM PATIENTS WITH SPORADIC LYMPHANGIOLEIOMYOMATOSIS (LAM) AND AN INVESTIGATION INTO THE RELATIONSHIP BETWEEN EVs SECRETED IN BLOOD AND PULMONARY FUNCTION

Kissane H¹, Keane MP^1,2, McCarthy C^1,2, Jouida A^1,2

¹UCD School of Medicine, University College Dublin, Ireland

²UCD Conway Institute of Biomedical and Biomolecular Research, University College Dublin, Ireland

LAM is a rare cancer that affects females of childbearing age. It is characterised by the proliferation of abnormal smooth-muscle-like cells and resultant cystic destruction of the lung and obstruction of the lymphatic system. EVs are small lipid-bilayer-bound particles, ranging from 30–150 nm in diameter, that are released by most cells into the extracellular space. EVs have been shown to carry proteins, nucleic acids, lipids and other cargo - facilitating intercellular communication and thus influencing physiological and pathological states. This research aimed to investigate the role of EVs in the pathogenesis of LAM with a view to better understand the diagnostic and disease-monitoring potential of EVs.

By differential centrifugation, EVs were isolated from the serum of LAM patients (n = 27) and healthy controls (n = 33). Nanoparticle tracking analysis was used to determine the number and size of EVs in patients' serum. Western blotting with positive markers CD63 and CD81 and negative marker calnexin was used to confirm the presence of EVs, using A549 cell lysates as a control. Data was analysed using Graphpad Prism Software with p-value < 0.05 deeming findings statistically significant.

It was found that serum from LAM patients contained increased numbers of EVs compared to that of healthy females. A negative correlation was established between the number of EVs in LAM patients' serum and their forced expiratory volumes (FEV₁).

This project's findings are sufficient to suggest EVs contribute to the pathogenesis of LAM. Further studies are required for insight into the mechanisms through which EVs exert this role.

Presenting Author:Hanna Kissane

Supervisor:Dr Amina Jouida

Co-supervisor:Assoc Prof Cormac McCarthy

EXPLORING THE ROLE OF EXTRACELLULAR VESICLES IN THE PATHOGENESIS OF IDIOPATHIC PULMONARY FIBROSIS (IPF)

Loh JW¹, Keane MP^{1, 2}, McCarthy C^{1, 2}, Jouida A^1,2

¹UCD School of Medicine, University College Dublin, Ireland

²UCD Conway Institute of Biomedical and Biomolecular Research, University College Dublin, Ireland

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease characterized by excessive scarring and accumulation of extracellular matrix within the pulmonary parenchyma, leading to impaired lung function and respiratory failure [1]. In recent years, extracellular vesicles (EVs), ranging in size from 30-150 nm, have emerged as key players in intercellular communication and garnering great attention due to their potential involvement in both normal physiological processes and pathological conditions. Its lipid bilayer membrane transports bioactive molecules (including pro-fibrotic signals) between cells, influencing fibroblast activation, myofibroblast differentiation, and extracellular matrix deposition [2]. The aim of this research was to investigate the role of EVs in IPF.

After the isolation of EVs from IPF patients’ serum using ultracentrifugation, they were subsequently characterized by western blotting and nanotracking analysis. The level of activity of metalloproteases (MMPs) in exosomes was then evaluated by zymography and compared to that of a healthy population.

The findings show a significant difference between controls and IPF patients in terms of EV concentration, with the latter having a greater concentration (p-value = 0.0330). Zymography further demonstrates a trend for an increase in MMP-2 and -9 activity in IPF patients.

This suggests that circulating EVs contribute to the proinflammatory environment that characterizes IPF. MMP-containing EVs can influence the balance between matrix synthesis and degradation. By targeting the secretion, content, or uptake of EVs, it may be able to attenuate the fibrotic and inflammatory processes that drive IPF progression, ultimately offering new avenues for therapeutic intervention in this condition.

References:

• 1. Meltzer EB, Noble PW. Idiopathic pulmonary fibrosis. Orphanet Journal of Rare Diseases. 2008; 3(1).

• 2. Yang Y, Liu Y, Chai Y, Liu K, Hu W, Zhao K, et al. Exosomes in pathogenesis, diagnosis, and treatment of pulmonary fibrosis. Frontiers in Pharmacology. 2022; 13:927,53.

Presenting Author: Jia Wei Loh

Supervisor: Dr Amina Jouida

Co-Supervisor: Assoc Prof Cormac McCarthy

EXTRACELLULAR VESICLE (EV) CHARACTERIZATION FROM TUBEROUS SCLEROSIS COMPLEX-LYMPHANGIOLEIOMYOMATOSIS (TSC-LAM) PATIENTS

Gooi ZC¹, Keane MP^1,2,3, McCarthy C^1,2,3, Jouida A²

¹UCD School of Medicine, University College Dublin, Ireland

²UCD Conway Institute of Biomedical and Biomolecular Research, University College Dublin, Ireland

³Department of Respiratory Medicine, St. Vincent’s University Hospital, Dublin, Ireland

Lymphangioleiomyomatosis (LAM) refers to a progressive lung disorder that occurs predominantly in women. It is characterized by an uncontrolled proliferation of smooth muscle cells within the lung, resulting in cystic lung destruction. LAM is commonly described in two forms: when it manifests concurrently with tuberous sclerosis complex (TSC), TSC-LAM, and when it arises sporadically, S-LAM. Extracellular vesicles (EVs), ranging from a size of 30 to 150 nm, have been described to play roles in the pathogenesis of various conditions. These nano-sized extracellular vesicles transfer an abundance of signalling molecules that play significant roles in cell communication and therefore, present a possibility as candidates of diagnostic biomarkers and therapeutic agents for LAM. Thus, our research aims to compare the quantity and characteristics of EVs between the plasma of TSC-LAM and healthy individuals.

First, EVs were isolated from the blood plasma of healthy and TSC-LAM individuals using ultracentrifugation. The size distribution and relative concentration of EVs between both populations were then assessed and compared by nanoparticle tracking analysis. Finally, following protein quantification via BCA assay, the protein content of these EVs were analysed by western blotting.

Results demonstrate that plasma EV levels were significantly higher in patients with TSC-LAM than in healthy individuals, which confirms the involvement of EVs in its pathological development.

Although the specific role of EVs in LAM remains unclear, this study provides a new exploration and foundation for further investigations to explore the potential applications of EVs as biomarkers, contributing to the diagnosis and overtime, treatment of TSC-LAM.

Presenting author: Gooi Zi Chieh

Supervisor: Dr Amina Jouida

Co-supervisor: Assoc Prof Cormac McCarthy

WATERSPORTS INCLUSION GAMES: THE BENEFITS FOR PARTICIPANTS AND THE IMPACT OF COVID-19 ON ACCESS

Killalea M¹, Warraitch A¹, Murphy J², Barrett E³

¹UCD School of Medicine, University College Dublin, Ireland

²Irish Sailing, Watersports Inclusion Games, Dublin Ireland

³Children's Health Ireland, Children's University Hospital, Temple Street, Ireland

The Watersports Inclusion Games is a free annual weekend event, where young people with a range of physical and intellectual disabilities and their families/siblings participate in various inclusive watersports activities.

This study aims to assess the psychological benefits of watersports for young people with various physical and intellectual disabilities and investigate the extent of the impact of the COVID-19 pandemic on their access to watersports. Following a literature review, a quantitative and qualitative survey was constructed using SurveyMonkey and circulated to the parents/guardians of participants three times following the event. The survey was completed anonymously on an opt-in basis and 28 responses that met our criteria for analysis were collected. Qualitative data from free-text responses were grouped under themes and quantitative data was analysed using SPSS.

Despite 64% (n = 18) of respondents indicating that their disability increased their vulnerability to COVID-19 in some capacity, the effect of the pandemic on accessibility was not statistically significant. This could be due to the small response number, or the everyday limitations participants faced prior to the pandemic. 92% (n = 25) of participants indicated that there was great inclusion in the watersports activities and that they were “very beneficial” regarding the possibility of the whole family’s participation [p = 0.005].

Full-family participation and accessibility of activities were key facilitators to the enjoyment and benefit of participants. Programmes should be established that allow able-bodied siblings and young people with disabilities to participate in the same activities.

Reference:

• 1. Watersports Inclusion Games [Internet]. [cited 2023 Jul 25]. Available from: https://www.sailing.ie/Events/Watersports-Inclusion-Games

Presenting Author: Méabh Killalea

Supervisor: Dr Elizabeth Barrett

Co-supervisor: Dr Johanne Murphy

EVALUATION OF THE RATES AND CLINICAL PROFILE OF YOUTH WITH EATING DISORDERS (ED) REFERRED TO ED SERVICE PRE AND POST COVID-19 PANDEMIC

Rafferty C¹, Lehman O², Butler E², Clifford M², McNicholas F^1,2,3

¹UCD School of Medicine, University College Dublin, Ireland

²Lucena Child and Adolescent Mental Health Services, Saint John of God Hospital, Dublin, Ireland

³Children's Health Ireland (CHI) at Crumlin, Dublin, Ireland

The COVID-19 pandemic had a negative impact on the mental health of children internationally [1], including those with eating disorders (EDs). Numbers of ED presentations for children and adults increased in Ireland following the pandemic [2]. We aim to establish whether this has persisted and if there has been any change in the clinical profile of patients following the pandemic.

Retrospective chart review was performed for all ED referrals to a specialist outpatient ED service. The study population included all children aged < 18 referred to the service. Data extraction was carried out following ethical approval. Anonymised data was extracted on to a proforma, then inputted to the Statistical Package for Social Sciences (SPSS) for analysis.

All referrals from January 2018 to October 2022 were included in the study (n = 177). 91.5% were female, with a mean age of 14.53 years. There was a significant increase in the referral rate post-COVID-19 (3.72 referrals/month vs 2.23 referrals/month, p = 0.012). Patients referred post-COVID-19 had a significantly higher IBW% at assessment (88.5% vs 82.7%, p = 0.001), a lower proportion were prescribed SSRI medication (23.5% vs 43.1%, p = 0.008), and a lower proportion had a comorbid mood disorder (37.0% vs 56.9%, p = 0.012).

This data suggests there has been an increase in referral rates for EDs in children and adolescents post-COVID-19. However, time-series analysis would be required to ascertain whether this increase is due to COVID. The data suggests changes in the clinical profile of referrals including mood disorder comorbidity and the number prescribed SSRI medication.

Acknowledgements

The author would like to acknowledge funding from the Health Research Board.

Ethical Approval

This research received ethical approval from the St John of God’s Hospitaller Services Research Ethics Committee (ID 827).

References:

• 1. Jones EAK, Mitra AK, Bhuiyan AR. Impact of COVID-19 on Mental Health in Adolescents: A Systematic Review. Int J Environ Res Public Health. 2021;18(5):2470.

• 2. O’Driscoll JD, Jennings R, Clifford M, Maher C, Corbett M, Wade S, et al. HSE National Clinical Programme for Eating Disorders in Ireland: COVID‐19 pandemic and eating disorder care in a new national eating disorder service. Int J Eat Disord. 2023;https://doi.org/10.1002/eat.23966.

Presenting Author: Cathal Rafferty

Supervisor: Prof Fiona McNicholas

Co-Supervisor: Dr Michelle Clifford

CHART REVIEW OF GP REFERRALS TO CHILD AND ADOLESCENT MENTAL HEALTH SERVICES (CAMHS) DURING COVID-19

George A¹, Lynch F², McNicholas F^1,3,4

¹UCD School of Medicine, University College Dublin, Ireland

²Saint John of God Community Mental Health Services, Lucena Clinic Tallaght, Dublin, Ireland

³Saint John of God Community Mental Health Services, Lucena Clinic Rathgar, Dublin, Ireland

⁴Children's Health Ireland, Crumlin, Dublin, Ireland

Since the onset of COVID-19, there has been a global increase in primary care referrals to child and adolescent mental health services (CAMHS). This is the first study to report on a 4–5 year cohort of general practitioner (GP) CAMHS referrals. The aim of this study is to examine the numbers and reasons for GP referral to CAMHS and examine pre-COVID-19, and persistent COVID-19 periods.

Following ethical approval, accepted referrals to one CAMH service were identified between January 2019 and June 2023. Clinical data was extracted from electronic health records, anonymised for data entry and analysed.

Of 995 accepted referrals, 249 were in the Pre-Covid, and 746 in the Covid onset cohort. The proportion of females referred increased, from 50.2% to 61.4%, (p < .001). Clinic prioritisation of referrals increased after COVID-19, from 41.0% to 54.2% (p < .001). Significant increases in internalising type symptoms from 78.0% to 68.7% (p = .004), eating disorders from 0.0% to 6.2% (p < .001), and self-harm/overdose from 18.5% to 35.8% (p < .001). Significant decreases in both ASD (26.5% to 18.2%, p = .007) and behavioural/ conduct disorders (22.5% to 13.5%, p = .001) were observed. Over the pandemic, male referrals for anxiety and thoughts of self-harm/suicidal ideation increased (p = .004; p = .037); female referrals for eating disorders and self-harm/overdose increased (p < .001; p < .001).

Given the persistence in internalising type symptoms and varying mental health needs between sexes, the benefits of increasingly tailored clinical interventions for CAMHS should be explored.

Table: Symptom Profiles of Referrals during COVID-19

Symptom Profile	Pre-covid (Jan 2019 – Feb 2020) N = 249 n (% within pre-covid)	Covid Onset (Mar 2020 – June 2023) N = 746 n (% within covid)	Statistics: Chi square (degrees of freedom or df, n = sample size) = chi value, p = p value with < .05 significance value
Anxiety Disorder	107 (43.0)	396 (53.1)	Chi square (1, n = 995) = 7.236, p = .006
Eating Disorder	0 (0.0)	46 (6.2)	Chi square (1, n = 995) = 14.730, p < .001
Autism Spectrum Disorder	66 (26.5)	136 (18.2)	Chi square (1, n = 995) = 7.399, p = .007
Behavioural/Conduct Disorder	56 (22.5)	101 (13.5)	Chi square (1, n = 995) = 10.592, p = .001
Thoughts of Self Harm/ Suicidal Ideation	95 (38.2)	331 (44.4)	Chi square (1, n = 995) = 2.699, p = .100
Self-Harm/ Overdose	46 (18.5)	267 (35.8)	Chi square (1, n = 995) = 25.167, p < .001
Internalising Type Symptoms	171 (68.7)	582 (78.0)	Chi square (1, n = 995) = 8.350, p = .004
Externalising Type Symptoms	86 (34.5)	208 (27.9)	Chi square (1, n = 995) = 3.660, p = .056

Presenting Author: Ankita George

Supervisor: Prof Fiona McNicholas

Co-Supervisor: Dr Fionnuala Lynch

EXAMINING THE IMPACT OF COVID-19 ON EATING DISORDER REFERRAL RATES AND CLINICAL PROFILE: A RETROSPECTIVE COHORT STUDY

O’Donnell A¹, Phair E¹, McCarra E², Haran M², McNicholas F^1,2

¹UCD School of Medicine, University College Dublin, Ireland

²Our Lady’s Children’s Hospital Crumlin, Dublin, Ireland

Recent studies suggest increased rates of eating disorder (ED) post-onset COVID-19, with concerns re increased medical comprise.^1,2 This study examines rates and clinical profile among paediatric referrals in the Republic of Ireland (ROI).

Following ethical approval, a retrospective chart review was conducted of 192 ED presentations to a paediatric hospital. The pre-COVID-19 period was studied from January 2018 to February 2020; post-COVID-19 was studied from March 2020 to June 2023. Statistical analysis (Chi-squared test, independent T-tests) was conducted using SPSS.

Our study population was 77.6% female of mean age 13.95. Most patients had AN (63.5%), followed by OSFED (15.6%), other/unknown (13.6%), ARFID (6.3%) and BN (1.0%). The mean IBW at admission was 83.16%, and 85.60% upon discharge. Referrals post-COVID-19 did not differ in terms of gender, age or admission/discharge IBW. COVID-19 saw higher monthly ED referral rates (1.46/month vs. 3.85/month, p < .001). Notably, OSFED referrals increased proportionally relative to other ED types (2.6% vs. 18.8%, p = .027). COVID-19 correlated with an increase in ED patients with self-harm (2.6% to 17.5%, p = .038). Despite increased self-harm, there was no change in the frequency of ED patients presenting with comorbid mood and/or anxiety disorders.

This study supports international data reflecting an increase in referrals for all types of ED post-COVID-19.¹ Higher rates of OSFED might suggest broader impacts of COVID-19. Higher rates of self-harm identified are concerning and need further study. Ongoing surveillance is required and should be accompanied by adequate resourcing to ensure access to care.

References:

• 1. O Driscoll, David, et al. “HSE National Clinical Programme for Eating Disorders in Ireland: COVID‐19 Pandemic and Eating Disorder Care in a New National Eating Disorder Service.” International Journal of Eating Disorders, 25 Apr. 2023, pubmed.ncbi.nlm.nih.gov/37097813/, https://doi.org/10.1002/eat.23966. Accessed 7 May 2023.

• 2. Spettigue, Wendy, et al. “The Impact of COVID-19 on Adolescents with Eating Disorders: A Cohort Study.” Journal of Eating Disorders, vol. 9, no. 1, 4 June 2021, jeatdisord.biomedcentral.com/articles/https://doi.org/10.1186/s40337-021-00419-3, https://doi.org/10.1186/s40337-021-00419-3. Accessed 18 July 2023.

Presenting Author: Angela O’Donnell

Supervisor: Dr Maeve Haran

Co-Supervisor: Prof Fiona McNicholas

THE ONGOING IMPACT OF COVID-19 ON THE RATES AND NATURE OF ACUTE PSYCHIATRY PRESENTATIONS TO A PAEDIATRIC EMERGENCY DEPARTMENT

Phair E¹, O’Donnell A¹, Haran M^{1, 2}, McMahon S², McNicholas F^1,2,3

¹UCD School of Medicine, University College Dublin, Ireland

²Department of Psychiatry, Children’s Health Ireland, Crumlin, Dublin, Ireland

³Saint John of God Community Mental Health Services, Lucena Clinic Rathgar, Dublin, Ireland

Mental health disorders are an increasingly prevalent cause of child and adolescent morbidity and mortality today¹. Internationally, COVID-19 has been linked with an adverse impact on adolescent mental health and has led to increased referrals to emergency departments². This report analyses the ongoing impact of COVID-19 on the rates and nature of acute mental health presentations in Ireland, with reference to a Dublin based paediatric emergency department.

Patient data was collected for the period January 2018– June 2023 and anonymised for export to SPSS. Descriptive and inferential statistical analyses were run to get a clinical profile of the presentations and any significant changes post COVID-19.

There has been a steady upward trend in rates of presentations over the past five and a half years, increasing significantly from 2021. The post COVID cohort had significantly more females, were slightly older on average, with more presenting outside of normal working hours and fewer admitted. Notably, suicidal ideation increased as a factor in presentation from 48 to 62%. When correlated with the advent of COVID this was found to be statistically significant. Similarly, presence of self-harm increased by 25% to being present in 69% of all acute psychiatry cases presenting after March 2020 (see Table 1).

These statistics allow an inference of association between increased suicidal ideation and self-harm and the advent of COVID-19. These results also concur with the existing evidence that COVID had a more significant impact on female and older acute mental health patients², with presentation types characterised by elevated self-harm reflecting that.

Table 1

Measures of significance for correlation between pre and post COVID in acute psychiatry presentations for key variables from January 2018- June 2023

References:

• 1. Castelpietra G, Knudsen AK, Agardh EE, Armocida B, Beghi M, Iburg KM, et al. The burden of mental disorders, substance use disorders and self-harm among young people in Europe, 1990–2019: Findings from the global burden of disease study 2019. The Lancet Regional Health - Europe. 2022;16:100341. https://doi.org/10.1016/j.lanepe.2022.100341

• 2. Wong BH-C, Cross S, Zavaleta-Ramírez P, Bauda I, Hoffman P, Ibeziako P, et al. Self-harm in children and adolescents who presented at emergency units during the COVID-19 pandemic: An International Retrospective Cohort Study. Journal of the American Academy of Child & Adolescent Psychiatry. 2023; https://doi.org/10.1016/j.jaac.2022.11.016

Presenting Author: Emma Phair

Supervisor: Dr Maeve Haran

UNRAVELLING THE IMPACT OF SEDENTARY BEHAVIOUR ON KNEE PAIN SEVERITY USING THE UK BIOBANK

Lee TCS¹, Hall M²

¹UCD School of Medicine, University College Dublin, Ireland

²UCD Conway Institute of Biomedical and Biomolecular Research, University College Dublin, Ireland

Knee osteoarthritis (OA) is a condition that causes structural alteration, functional impairment, and pain of the knee. Although it is known that sedentary behaviour serves as a predictor for the presence of knee OA¹, less is known about its effect on joint pain. Hence, this study aims to test the hypothesis that sedentary behaviour is associated with knee OA pain severity.

Data from 42,593 participants in the UK Biobank who experienced knee pain for ≥ 3 months were used. Ordered logistic regression models were used to determine the cross-sectional association between accelerometer-derived sedentary time and self-reported sedentary time and knee pain severity. Models were adjusted to account for potential confounders including age, sex, BMI, ethnicity, education, employment, self-rated health, Townsend index, smoking and alcohol status, anxiety/depression, number of pain sites, pain interference with activity, and degree of relief from pain medications.

For accelerometer-derived sedentary time, the unadjusted odds ratio of having more severe knee pain with increasing time in sedentary behaviour was 1.00 (95% CI 1.00–1.00), while the adjusted odds ratio was 1.00 (95% CI 1.00–1.00). For self-reported sedentary behaviour, the unadjusted odds ratio was 0.97 (95% CI 0.94–1.00), while the adjusted odds ratio was 0.97 (95% CI 0.94–1.01).

Current recommendations for the management of patients with chronic joint pain focus on increasing engagement in physical activity. These results question whether reducing time in sedentary behaviour is likely to have an impact on knee pain severity.

Acknowledgement:

The author would like to acknowledge funding from the Health Research Board’s Summer Student Scholarship.

Reference:

• 1. Cao Z, Li Q, Li Y, Wu J. Causal association of leisure sedentary behavior with arthritis: A Mendelian randomization analysis. Seminars in arthritis and rheumatism. 2023; 59, 152171

Presenting Author: Tze Ching Shania Lee

Supervisor: Dr Michelle Hall

EVALUTION OF PARENTS PLUS PARENTING PROGRAMME DELIVERED TO PARENTS OF CHILDREN WITH 22Q11.2DS

Khan K¹, Gadancheva V², Mulcahy W³, Kelleher S³, McNicholas F^{1, 2}

¹UCD School of Medicine, University College Dublin, Ireland

²Department of Psychiatry, Children’s Health Ireland, Crumlin, Dublin, Ireland

³Department of General Paediatrics, Children’s Health Ireland, Crumlin, Dublin, Ireland

The aim of this study was to evaluate the effectiveness of Parents Plus Children’s Programme (PPCP) as a parenting intervention for parents of children with 22q11.2DS who experience behavioural difficulties. PPCP is an evidence-based parenting programme developed in Ireland and delivered widely in the community.

A group of eight parents of children aged 6–12 years with 22q11.2DS were invited to participate in PPCP that included 8 sessions delivered online. Five parents completed the programme. Questionnaires (Strengths and Difficulties Questionnaire SDQ, Parental Stress Scale PSS, Kansas Parental Satisfaction Scale KPSS) were administered at three different time points: prior to (T1), immediately after (T2), and at six-month follow-up (T3). Parents were asked to identify individual and child-related goals. SPSS vs27 was used for statistical analysis to determine significance.

Mean baseline SDQ score was 18.2 (SD 5.07), PSS – 38.2 (SD 7.36), KPSS – 13.8 (SD 3.27). No significant difference at baseline T1, post-intervention T2 and the six-month follow up SDQ, PSS and KPSS scores was found. Parents moved significantly towards achieving their individual and child-oriented goals. 6-monthly follow-up data collection is currently in progress. Parents found value in sharing their experiences with other parents of children with 22q11.2DS and being part of a support group.

This pilot study demonstrated potential feasibility and benefits for parents attending the group. The small group sample is a limitation of this study and ongoing evaluation is planned.

Presenting Author: Ahmed Zafar Khan

Supervisor: Dr Veselina Gadancheva

Co-Supervisors: Mr Wesley Mulcahy & Prof Fiona McNicholas

INVESTIGATING THE BENEFITS TO MOTHERS OF BREASTFEEDING SUPPORT PROVIDED BY LA LECHE LEAGUE OF IRELAND

Ryan S¹, Warraitch A¹, Bird M², Barrett E¹

¹UCD School of Medicine, University College Dublin, Ireland

²La Leche League of Ireland

Breastfeeding rates in Ireland are amongst the lowest in the world falling short of the WHO’s guidelines for infant feeding. Breastfeeding is associated with improved maternal and infant health and reduced healthcare costs. Breastfeeding support groups are associated with improved breastfeeding outcomes. The aim of this study was to identify the benefits of breastfeeding peer support groups in Ireland for mothers availing of them.

This was a mixed-methods study involving the design and circulation of an anonymous opt-in survey of adult volunteers, namely mothers who have breastfed, are currently breastfeeding or intend to breastfeed with the support of La Leche League of Ireland (LLL-Ireland). Qualitative data was analysed using thematic analysis and quantitative data was analysed using Excel, and SPSS where several questions were exported to perform Chi-Square Analysis.

With LLL-Ireland’s support, mothers have met their breastfeeding goals, made friends, received help for breastfeeding-related issues, found a sense of community and improved their confidence to breastfeed. The combination of online and in-person support is most beneficial as it allows mothers to access immediate support 24/7, while also providing an opportunity to seek practical, hands-on advice and socialise.

Given the varied and numerous benefits associated with LLL-Ireland’s support, its promotion through national media and referrals from healthcare professionals would increase awareness of supports available to parents, which could result in greater use of this resource, eventually translating to higher breastfeeding rates in Ireland, and thus better maternal and infant health and reduced healthcare costs.

References:

• 1. Management Data Report. [Internet]. HSE; December 2020 [cited 2023 Aug 27]. Available from: https://www.hse.ie/eng/services/publications/performancereports/management-data-report-december-2020.pdf. Infant and young child feeding [Internet].

• 2. World Health Organisation; 2021 [cited 2023 Aug 27]. Available from: https://www.who.int/news-room/fact-sheets/detail/infant-and-young-child-feeding

Presenting Author: Sorcha Ryan

Supervisor: Dr Elizabeth Barrett

THE PSYCHIATRIC PROFILE OF CHILDREN WITH 22Q11.2 DELETION SYNDROME ATTENDING CHI AT CRUMLIN

Yee RL¹, Gadancheva V¹, McNicholas F¹

¹UCD School of Medicine, University College Dublin, Ireland

22q11.2 Deletion Syndrome (22q11.2 DS) is among the most common microdeletion syndrome, associated with a myriad of physical and psychiatric manifestations [1, 2]. This study aims to highlight the prevalence of psychiatric conditions associated with 22q11.2 DS in a paediatric population. Using a software called SPSS, descriptive statistical analyses of the psychiatric profiles of 96 patients who attended an integrated 22q clinic from 2016–2023 were performed. The ICD10 and Child Behaviour Checklist questionnaires (CBCL) were used to assess the psychiatric health of the patients. Out of the 96 patients, 84 assessments were completed, with 11 patients requiring multiple assessments. 26 patients were excluded due to non-attendance or had declined their assessment.

40.5% (n = 34) of assessments had an axis 1 diagnosis of anxiety, for which no significant difference was apparent between both genders, followed by 21.4% (n = 18) with ADHD, and 3.6% (n = 3) with autism. 29.8% (n = 25) of assessments did not receive any axis 1 diagnosis. 6 patients had a family history of 22q11.2 DS, and 58.3% (n = 49) reported a family history of psychiatric illnesses. For the CBCL total problems category, 22.6% (n = 19) of patients were in the clinical range.

These results signify the high prevalence of psychiatric conditions in children with 22q11.2 DS and should encourage physicians to place more emphasis on the psychiatric manifestations of this syndrome, as with its other symptoms.

References:

• 1. Bertrán M, Tagle FP, Irarrázaval M. Psychiatric manifestations of 22q11.2 deletion syndrome: A literature review [Internet]. Elsevier; 2018 [cited 2023 Jul 31]. Available from: https://www.sciencedirect.com/science/article/pii/S2173580817301645

• 2. Morris E, Inglis A, Friedman J, Austin J. Discussing the psychiatric manifestations of 22q11.2 deletion syndrome: An exploration of clinical practice among medical geneticists [Internet]. Elsevier; 2013 [cited 2023 Jul 31]. Available from: https:// www.sciencedirect.com/science/article/pii/S109836002102726X?via%3Dihub

Presenting Author: Yee Rae Lyz

Supervisor: Prof Fiona McNicholas

Co-supervisor: Dr Veselina Gadancheva

EXPLORING THE CONCEPT OF SENSITIVE HEALTH INFORMATION FROM THE PATIENT PERSPECTIVE AND THE FACTORS THAT MAY INFLUENCE ITS COLLECTION, USE, AND SHARING

Abu Shehab S¹, Flaherty SJ²

¹UCD School of Medicine, University College Dublin, Ireland

²Health Information and Quality Authority, Cork, Ireland

Understanding patient perspectives is crucial in the context of healthcare data management and should be supported by robust methodologies. This collaborative research, led by Health Information and Quality Authority (HIQA) with support from Sadeer Abushehab, employs qualitative and thematic analyses. The study delves into patient perceptions and influential factors shaping sensitive health data dynamics.

Employing a mixed-method approach, including a national telephone survey and focus groups. Sadeer AbuShehab played a pivotal role in the qualitative analysis of 11 service-specific focus groups and meticulously reviewed and categorised data obtained from over 1000 national telephone survey responses. Employing thematic analysis; recurring patterns, sentiments, and underlying themes were identified from the qualitative data. Thematic analysis revealed noticeable themes, including "effective communication and trust," "nature of information and its consequences," and "recipient/relevance of information."

The first theme, "effective communication and trust," underscored patients' need for clear, honest, and comprehensible communication. The second theme, "nature of information and its consequences," emphasised that sensitivity often hinges on the potential outcomes of data sharing and highlighted that information that may carry a stigma is commonly considered sensitive. The third theme, "recipient/relevance of information," illuminated patient concerns about who receives their data and for what purpose.

Thematic analysis and a robust methodology, exposed crucial viewpoints, offering insights into participants' experiences. Sadeers’ role provided informed evidence-based recommendations towards the Irish Health Information management. Integrating qualitative findings with HIQA's expertise facilitated the identification of crucial improvements required to better care through the lens of sensitive health information.

Presenting Author: Sadeer Abu Shehab

Supervisor: Dr Sarah Jane Flaherty

QTC PROLONGATION AND ELECTROCARDIOGRAM ABNORMALITIES CAUSED BY ADHD MEDICATIONS AMONGST THE PAEDIATRIC POPULATION: A SYSTEMATIC REVIEW AND META-ANALYSIS

Scully R¹, Ritchie W², Ling C¹, McNicholas F²

¹UCD School of Medicine, University College Dublin, Ireland

²Childrens Health Ireland, Crumlin, Dublin, Ireland

Stimulant and non-stimulant medications have been used to treat Attention Deficit Hyperactivity (ADHD) in paediatrics successfully for decades. However, emerging evidence has raised concerns about their potential short and long-term side effects. This paper examines the concerns regarding their potential impact on cardiac health, specifically their potential link to the prolongation of the corrected QT interval (QTc) measured on an electrocardiogram (ECG).

This systematic review and meta-analysis aimed to assess the link between these medicines and changes in cardiovascular parameters. Particularly on the QTc interval, as well as other electrocardiogram (ECG) abnormalities that may be relevant to the treatment of ADHD.

We conducted a comprehensive, double-coded, systematic review spanning three major medical databases (SCOPUS, PubMed, Embase and Cochrane). Based on relevant keywords. A subsequent meta-analysis was conducted using Review Manager (RevMan, Version 5.4; Cochrane Collaboration, Oxford, United Kingdom).

Our study encompassed 48 research papers from over 7 different countries. A t-test analysis revealed a p-value exceeding 0.05, indicating a lack of statistical significance concerning drug-induced QTc prolongation. The results of our meta-analysis indicated that the standard mean difference between pre-treatment and post-treatment QTc intervals was -0.14, with a confidence interval of -0.21 to -0.06 (P > 0.05). Our data suggests no substantial association between QTc prolongation and ADHD medication. Furthermore, our findings suggest a low prevalence of ADHD drug-induced ECG abnormalities.

Based on the evidence and statistical analyses presented in this review, it can be concluded that ADHD medications appear to be safe for use in paediatric patients from a cardiovascular perspective, owing to a low risk of QTc prolongation or new ECG abnormalities. However, further research is necessary to assess the potential benefits of pre-treatment cardiovascular screening in relation to its cost-effectiveness and impact on services.

Presenting Author: Rhys Scully

Supervisor: Prof Fiona McNicholas

IMPACT OF THE CAMHS KERRY REVIEW AND MASKEY REPORT ON CLINICIAN VIEWS OF CHILD AND ADOLESCENT MENTAL HEALTH SERVICES (CAMHS)

Ong JZ¹, Bond L^1,2, McNicholas F^1,2

¹UCD School of Medicine, University College Dublin, Ireland

²Saint John of God Community Mental Health Services, Lucena Clinic, Dublin, Ireland

A report commissioned in 2021 by Dr Seán Maskey to look at concerns raised about the care provided by a non-consultant hospital doctor (NCHD) in South Kerry CAMHS. The report highlighted that the treatment to children were risky and did not meet the acceptable standards [1]. Based on this incident, we wish to explore clinicians’ views of the CAMHS service they work in and whether there is a shift in their behaviour towards prescription and monitoring practices of psychotropic medication since the publication of the report.

Following ethical approval, an anonymous online survey was sent out to all 160 CAMHS clinicians by the College of Psychiatrists of Ireland (63.8% response rate).

Post-Maskey, 92% of clinicians think that public perception of CAMHS has worsen. This has resulted in them shifting their prescribing approach towards psychotropic medication. This is evident in their behaviour towards polypharmacy. They are also more accountable to patients by seeking their consent before prescribing. About half of the clinicians think that NCHDs do not have adequate psychotropic treatment training. Clinicians also experienced an increase in stress and workload amidst a worsening staffing levels in the service.

Lack of proper training and supervision of NCHDs can be a factor causing clinicians to be less confident of their prescribing practices. With an increase in demand for the system after the COVID-19 pandemic, there is an urgent need to address the issue by drafting a national psychotropic medication guideline and putting in place good clinical governance in all CAMHS [2].

References:

• 1. Maskey S. Report on the Look-Back review into Child and Adolescent Mental Health Services County MHS Area A. Health Service Executive (HSE); 2022 Jan.

• 2. McNicholas F, Kelleher I, Hedderman E, Lynch F, Healy E, Thornton T, et al. Referral patterns for specialist child and adolescent mental health services in the Republic of Ireland during the COVID-19 pandemic compared with 2019 and 2018. BJPsych Open [Internet]. 2021 May;7(3). Available from: https://www.cambridge.org/core/journals/bjpsych-open/article/referral-patterns-for-specialist-child-and-adolescent-mental-health-services-in-the-republic-of-ireland-during-the-covid19-pandemic-compared-with-2019-and-2018/28B0BA5F1328BBEAC24D0FFD6C644FD3

Presenting Author: Jia Zhe Ong

Supervisor: Prof Fiona McNicholas

UNRAVELLING THE IMPACT OF SEDENTARY BEHAVIOR ON PAIN SEVERITY FOR ADULT PATIENTS WITH HIP OSTEOARTHRITIS

Tak Ying Ko L¹, Hall M¹

¹UCD School of Medicine, University College Dublin, Ireland

Osteoarthritis is a leading cause of pain and reduced quality of life. Sedentary behavior (SB) levels are also higher in the osteoarthritis patient population and is linked with worsening health outcomes. However, the impact of SB on the extent of pain in hip osteoarthritis is inconclusive from current literature. The purpose of our study is therefore to test the hypothesis that time in SB is associated with greater pain severity in people with chronic hip pain. Using the UK Biobank, 31,326 individuals (mean age 68.03 (7.33) years, 39.71% men) with chronic pain reported hip pain severity on a numeric rating scale (0–10). Pain was categorised as none, mild, moderate, and severe. SB was captured via a wrist-worn Axivity AX3 accelerometer worn by participants on their dominant wrist continuously for a 7-day period. Ordered logistic regression analyses were performed unadjusted and adjusted for covariates including age, sex, alcohol use, anxiety/depression, BMI, employment status, ethnicity, smoking status, pain treatment, presence of other pain sites, educational qualifications, self-perceived health and their Townsend deprivation index score. There was no significant association between time spent in SB and hip pain severity in either the unadjusted (odds ratio 2.32 (95% CI -0.97 to 5.51) or adjusted model (odds ratio 1.39 (95% CI -0.56 to 1.22). Results remained unchanged when using subjective measures of SB. Although SB reduction is desirable for many health outcomes, our cross-sectional data do not support the contention that less time in SB would reduce hip pain severity.

Presenting Author: Tak Ying Louise Ko

Supervisor: Assoc Prof Michelle Hall

MECHANISM OF ATRIAL FIBROSIS IN ATRIAL FIBRILLATION

Zhong C¹, Li RK²

¹UCD School of Medicine, University College Dublin, Ireland

²Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is a burden to healthcare systems globally [1]. Current management of AF involving antiarrhythmic pharmaceuticals and catheter ablation lack long-term efficacy. Thus, novel treatment approaches are needed, which requires an understanding of the mechanism behind AF. Central to the pathogenesis of AF is atrial fibrosis, which is the accumulation of extracellular matrix (ECM) in the atria. This project aims to summarize the current literature around the mechanism behind atrial fibrosis and potential therapies utilizing this knowledge.

Literature searches were conducted through Google Scholar and Web of Science.

The review found that major contributors to ECM homeostasis are fibroblasts, matrix metalloproteinases and tissue inhibitors of metalloproteinases. In response to profibrotic signals, fibroblasts proliferate and differentiate into myofibroblasts that secret ECM. Major profibrotic molecular signaling pathways include the renin–angiotensin–aldosterone system, transforming growth factor-β, platelet-derived growth factor, and connective tissue growth factor. Evidence suggests that inflammation and fibroblast ion channel abnormalities play important roles in the development of atrial fibrosis [2]. Non-coding RNA regulates atrial fibrosis through profibrotic molecular pathways at various levels. Pharmacological approaches to prevent atrial fibrosis utilizes heart failure medications, and agents being investigated include pirfenidone, tranilast, and sacubirtril/valsartan.

Agents that prevent atrial fibrosis are promising, but research is still in the early stages. Although much information has been obtained about the pathophysiology of atrial fibrosis, the precise mechanisms are not yet fully understood. A better understanding of atrial fibrosis could guide discovery of pharmacological targets and novel therapies that prevent AF.

References

• 1. Hindricks G, Potpara T, Dagres N, Arbelo, E, Bax JJ, Blomstro¨m-Lundqvist C, et al. 2020 ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2021; 42(5): 373–498.

• 2. Sygitowicz G, Maciejak-Jastrzebska A, Sitkiewicz D. A review of the molecular mechanisms underlying cardiac fibrosis and atrial fibrillation. J Clin Med. 2021; 10(4430).

Presenting Author: Christina Zhong

Supervisor: Dr Ren-Ke Li

A PILOT STUDY OF ADJUSTMENT DISORDER IN PHYSICAL ILLNESS: FACTOR ANALYSIS AND CORRELATION WITH MEASURES OF DEPRESSION AND ANXIETY

Gordon S¹, Doherty AM^2,3

¹UCD School of Medicine, University College Dublin, Ireland

²Department of Psychiatry, School of Medicine, University College Dublin, Ireland

³Department of Liaison Psychiatry, Mater Misericordiae University Hospital, Dublin, Ireland

Adjustment disorder is regularly encountered in clinical practice, and the presence of a physical illness increases the likelihood of its development. This study aims to assess adjustment disorder, depression, and anxiety symptoms in the context of sociodemographic and clinical factors for patients with physical illnesses, and explore the factor structure of their respective screening questionnaires - Adjustment Disorder New Module-8 (ADNM-8), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder-7 (GAD-7).

Participants were recruited from oncology, endocrine, and back pain outpatient clinics in Dublin, Ireland (N = 51). Sociodemographic and clinical information was collected, and self-report measures of adjustment disorder, depression, and anxiety symptoms were administered. Data analysis consisting of Kruskal–Wallis H tests, correlation analysis, and exploratory factor analysis was conducted using SPSS v27 and Python 3.9.

The prevalence rates of adjustment disorder, depression, and anxiety were 11.76%, 7.9%, and 7.9% respectively. Participants with a history of psychiatric illness had significantly higher ADNM-8 and GAD-7 scores (p < 0.05), while never married individuals had higher PHQ-9 scores (p < 0.05). There was no significant effect of age, sex, education, illness type, or housing status. Symptoms of adjustment disorder, depression, and anxiety were all found to be highly correlated, and their questionnaires displayed 2-factor structures.

Individuals with a physical illness have high levels of adjustment disorder. Moreover, participants with a previous psychiatric condition had significantly higher rates of adjustment disorder and anxiety symptoms, suggesting symptoms persist post-recovery.

Acknowledgment:

The author would like to acknowledge funding from the Pillar Centre for Transformative Healthcare.

Presenting Author: Sean Gordon

Supervisor: Assoc Prof Anne Doherty

OPIOID EQUIANALGESIC RATIOS: A REVIEW OF PHARMACEUTICAL COMPANY GUIDANCE – TRANSDERMAL OPIOIDS

Yong L¹, Mansour Y¹, Taylor A², Davies A^1,2

¹UCD School of Medicine, University College Dublin, Ireland

²Academic Department of Palliative Medicine, Our Lady’s Hospice & Care Services, Harold's Cross, Dublin, Ireland

International guidelines are being developed to evaluate the medical literature for equianalgesic ratios (ratios used to convert the dose of one opioid drug to another). The aim of this project is to generate complementary information by examining Summary of Product Characteristics (SmPCs) produced by pharmaceutical companies for transdermal opioids.

Pharmaceutical companies producing transdermal “strong” opioids (i.e. buprenorphine, fentanyl) in Europe/USA were identified, and their SmPCs obtained from the Internet. Equianalgesic ratios were not available for the low dose (7 day) buprenorphine patches, but were available for the high dose (4 day) buprenorphine, and fentanyl patches. Emails were sent to each pharmaceutical company regarding the source of these ratios.

Table 1 Oral 24-h morphine doses for DUROGESIC doses as listed in SmPCs and calculated oral 24-h morphine doses based on recommended ratios

Eight buprenorphine patch companies were contacted, and only one replied saying that their product was bioequivalent to the original formulation. Five fentanyl patch companies were contacted, and 4 replied regarding how the ratios came about (although supporting information was not available). The ratio for the high dose buprenorphine patches were the same (oral morphine: transdermal buprenorphine, 1:75–115). The ratio for the fentanyl patches were also the same: 1:150 was recommended for patients needing opioid rotation, whereas 1:100 was recommended for patients on stable and well tolerated treatment. However, tables of equivalent doses within the fentanyl SmPCs suggested variable ratios (Table 1).

There is a lack of evidence for the equianalgesic ratios, meaning it is of paramount importance that healthcare providers exercise caution when utilizing these ratios, and should always individually titrate the dose.

Presenting Author: Lucas Yong

Supervisor: Prof Andrew Davies

Co-supervisor: Dr Amy Taylor

EVALUATING IMAGE QUALITY ON POST-MORTEM CARDIAC CT USING AN ANTHROPOMORPHIC PHANTOM

Molyneaux M¹, Davis M¹, Precht H^3,4,5

¹UCD School of Medicine, University College Dublin, Ireland

³Health Sciences Research Centre, UCL University College, Odense, Denmark

⁴Radiology Department, Lillebelt Hospital, University Hospitals of Southern Denmark, Kolding, Denmark

⁵Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark

Ischemic heart disease is a major cause of mortality worldwide, most commonly occurring due to atherosclerotic plaque rupture [1]. Coronary computed tomography angiography (CCTA) has been recognised as a potential procedure for identification and differentiation of these plaques. One method used to test the diagnostic accuracy of new technical developments on the CT scanner is post-mortem imaging, which does not carry the risk of a high radiation dose causing harm to the patient. The aim of this study was to compare image quality of CCTA on post-mortem hearts scanned inside an anthropomorphic phantom versus scanning directly on the scanner bed, and evaluate which image was most comparable to scanning in-vivo (living patients).

Ten post-mortem hearts were scanned using the two methods [2] and ten CCTA in-vivo were also taken for comparison. Region of interest (ROI) measurements of CT numbers for each scanning method were made and coronary vessel analysis measured plaque burden and composition.

A Wilcoxon Signed Rank test showed that ROI measurements from the two methods were significantly different. Mann–Whitney U tests showed a significant difference between the in-vivo measurements and the two post-mortem scanning methods. Wilcoxon Signed Rank tests indicated a significant difference for 4 out of 5 plaque measurements.

The results showed a significant difference in image quality between scans taken with the heart directly on the scanner bed compared to inside the phantom, with those inside the phantom being more comparable to in-vivo scans. This highlights the importance of using an appropriate scanning technique when imaging post-mortem organs.

Acknowledgment:

The author would like to acknowledge funding from Global Diagnostics Ireland Limited T/A Medica.

References:

• 1. Bergmark BA, Mathenge N, Merlini PA, Lawrence-Wright MB, Giugliano RP. Acute coronary syndromes. Lancet. 2022;399(10332):1347–58.

• 2. Precht H, Leth PM, Thygesen J, Hardt-Madsen M, Nielsen B, Falk E, et al. Optimisation of post mortem cardiac computed tomography compared to optical coherence tomography and histopathology – Technical note. Journal of Forensic Radiology and Imaging. 2014;2(2):85–90.

Presenting Author: Marissa Molyneaux

Supervisor: Dr Helle Precht

EXPLORING NEW TREATMENTS FOR BURKITT’S LYMPHOMA

Okpara A¹, O’Connor E², Halasz M^1,2

¹UCD School of Medicine, University College Dublin, Ireland

²Systems Biology Ireland, University College Dublin, Dublin, Ireland

Burkitt’s lymphoma (BL) is a high-grade non-Hodgkin lymphoma that represents the most common childhood cancer in equatorial Africa. Characterised by a balanced translocation involving MYC and the Immunoglobulin gene loci, overexpression of c-Myc is a key feature of the disease. With c-Myc being considered a challenging drug target, an alternative route to mitigate its effects might be explored through its protein–protein interactions.

The aim of this study was to (a) map the c-Myc interactome in BL, (b) determine the role of key interactors and (c) target selected interactors or their related effects using inhibitors.

The Raji BL cell line was cultured and analysed using co-immunoprecipitation/mass spectrometry (co-IP/MS) to determine c-Myc protein–protein interactions. MS data was analysed using Perseus and two sample t-tests (S0 = 0; p-value = 0.01) were employed to determine top c-Myc interactors. Gene ontology analysis with STRING database highlighted known and predicted interactions that may collaborate with c-Myc in lymphomagenesis. Nibrin and several splicing proteins were notable interactors. RNA splicing was selected as a therapeutic target for this study due to emerging evidence of its role in other haematological malignancies [1]. Raji cells seeded in 96-well plates were exposed to splicing inhibitor Isoginkgetin. After 3 days, cell viability was measured by the Cell Titre Glo assay. Dose–response curves were plotted, with a marked decrease in cell viability observed at higher doses of Isoginkgetin. EC50 was also calculated.

The results suggest a potential role for splicing inhibitors, Nibrin inhibitors, and PARP1 inhibitors to emerge as new therapies for BL.

Acknowledgment:

The author would like to acknowledge funding from the Pathological Society of Great Britain and Ireland.

References:

• 1. Yamauchi H, Nishimura K, Yoshimi A. Aberrant RNA splicing and therapeutic opportunities in cancers. Cancer Sci. 2022;113(2):373-81.

Presenting Author:Aghogho Okpara

Supervisor: Dr Melinda Halasz

Co-Supervisor:Dr Eoghan O’Connor

A STUDY TO INVESTIGATE SEARCH AND RESCUE DOGS’ ABILITY TO DETECT HUMANS USING TEETH IN A VARIETY OF ENVIRONMENTS

Benny T¹, Morris R², Davis M³

¹UCD School of Veterinary Medicine, University College Dublin, Ireland

²Wexford K9 Search and Rescue, Adamstown, Enniscorthy, Wexford, Ireland

³UCD School of Medicine, University College, Dublin, Ireland

Canine olfaction is a remarkable sensory system that has been applied in various domains including search and rescue (SAR) operations [1]. This study aimed to evaluate the performance of two SAR dogs in locating human teeth in different environments with the aid of 3 distinct experimental designs.

For the main experiment, we used a stainless-steel probe bar marked with intervals of 3 cm, 6 cm, and 9 cm to dig varying depths. A vial containing a tooth was placed inside the holes, and nine trials were conducted for each dog across the three depths and materials: soil, grass, and sand. Dog-handler pairs searched designated areas and dogs were rewarded upon successful detection. The search process was video recorded for subsequent analysis and measurement of detection efficacy.

The study findings confirm that human teeth are a viable scent source for SAR dogs. Mean detection times indicated that greater depths generally led to increased detection times, a finding consistent with previous canine olfactory research [2]. Certain anomalies, particularly in grass trials, may warrant further investigation.

This study contributed to the growing body of literature on canine olfactory detection, providing valuable insights into the effects of depth and material on detection time. The findings have practical implications for refining training and deployment strategies. Further research may involve a larger sample size, various dog breeds, different odorous substances, controls, and broader environmental conditions which may yield a more comprehensive understanding of the multifaceted nature of canine olfaction.

Acknowledgements:

The author would like to acknowledge funding from Medica. This project was made possible with the support of Wexford K-9 Search and Rescue.

References:

• 1. Jones A, Sommerville R, Mendl M, et al. Canine olfaction: physiology, behavior, and possibilities for practical applications. Animals. 2018;8(10):161

• 2. Gazit, I., Goldblatt, A., & Terkel, J. Animal Cognition. 2005;8(3):143–150.

Presenting Author: Theresa Benny

Supervisor: Dr Michaela Davis

PEDIATRIC RENAL ARTERY STENOSIS: MID-TO LONG-TERM OUTCOMES FOLLOWING RENAL ARTERY ANGIOPLASTY

Youssef S¹, Hawkins CM^2,3, Shah JH^2,3, Kennedy SS^3,4, Riar SK^3,4, Gill AE^2,3

¹UCD School of Medicine, University College Dublin, Ireland

²Department of Radiology and Imaging Sciences, Division of Interventional Radiology and Image - Guided Medicine, Emory University School of Medicine, Atlanta, Georgia, USA

³Emory and Children’s Pediatric Institute, Children’s Healthcare of Atlanta at Egleston, Atlanta, Georgia, USA

⁴Division of Pediatric Nephrology, Department of Pediatrics, Emory University School of Medicine and Children’s Healthcare of Atlanta, Atlanta, Georgia, USA

To investigate the efficacy, safety, and durability of renal artery angioplasty for pediatric renal artery stenosis (RAS) at a tertiary-care hospital.

Clinical data of patients (blood pressure, anti-hypertensive medications, imaging, and procedural details) who underwent angioplasty for RAS from July 2014-May 2023 were retrospectively analyzed.

Angiography was performed in 74 children, mean age = 10.6 years (range = 3mos—20y). Mean follow-up = 2.5 years (range, 4d -10.4y). 45 angioplasty procedures were performed on 28 patients. 11 (39.3%) cured (normotensive, no anti-HTN meds), 10 (35.7%) improved (improved BP, decreased anti-HTN dose or # of meds), and 7 (25%) failed (no improvement) following 1st angioplasty. Of the 17 patients who improved/failed, 12 had 2nd angioplasty. Of those, 3 (25%) were treated with cutting-balloons. 2 (16.7%) cured, 8 (66.7%) improved, and 2 (16.7%) failed. 5 had a 3rd angioplasty. 4 (80%) were treated with cutting-balloons. 3 (60%) cured, 2 (40%) improved. In sum, 16/28 (57.1%) of patients were cured, and 12/28 (42.9%) were improved. 19 patients with abnormal angiography had normal CTA (10), MRA (3), and US (17). 14 patients with normal angiography had abnormal CTA (4), MRA (2), and US (13). Major complication rate = 8.9% (4/45). (1) Renal artery stent (19 mos following curative angioplasty) with residual stenosis, (2) arterial extravasation following cutting-balloon, (3) arterial dissection, and (4) vasospasm, partially resolved with nitroglycerin/TPA.

Angioplasty is an efficacious procedure in the setting of pediatric RAS. Angiography should be pursued when RAS is suspected, as imaging is commonly discordant with angiography.

Acknowledgement:

The author would like to acknowledge funding and support from the University College Dublin School of Medicine SSRA Gaensler Scholarship.

Presenting Author:Salma Youssef

Supervisor: Dr C Matthew Hawkins

PLASTICITY IN BIOLOGICAL AGE

Douglas D¹, MrÇela A², Lahens N², FitzGerald GA², Skarke C²

¹UCD School of Medicine, University College Dublin, Ireland

²Institute for Translational Medicine and Therapeutics (ITMAT), University of Pennsylvania Perelman School of Medicine, Philadelphia, USA

Biological age can be estimated from distinct methylation patterns of DNA [1], where methyl groups attach to cytosine bonded with a guanine, known as a CpG site. CpG methylation commonly occurs in promoter regions resulting in gene regulatory effects [2].

The aim of this research is to determine (1) the extent of diurnal oscillation in predicted biological age based on DNA methylation changes, (2) age-specific differences in rhythmic methylation patterns, and (3) most significant oscillators among methylation sites and their predicted functional impact on gene expression.

Ten young and old subjects were enrolled and phenotyped over two days including biosampling in 12 h intervals (day 1) followed by 4 h intervals (day 2). DNA methylation was quantified using bisulfite sequencing on Illumina's Infinium MethylationEPIC v1.0 BeadChip Kit from peripheral blood buffy coat samples. An “Epigenetic clock” was trained on 2000 subjects with methylation data publicly available from the Altumage [1] clock using Elastic Net. This clock was applied to the subjects’ methylation data, with any missing values imputed by age group, to give a predicted age of each subject at each time point. Oscillation significance was calculated using cosinor analysis.

First results identified subject-level oscillations of the epigenetic clock and found that diurnal variability of biological age emerged predominantly among the old. This suggests that biological age estimated from DNA methylation exhibits age-dependent short-term fluctuations. Current work is identifying which CpG sites drive these oscillations, and what their impact on gene function is.

Acknowledgment:

This author would like to acknowledge funding from the 2023 UCD School of Medicine Dean's Scholarship.

References:

• 1. de Lima Camillo, L. P., Lapierre, L. R., & Singh, R. (2022). A pan-tissue DNA-methylation epigenetic clock based on deep learning. Npj Aging, 8(1), 4. https://doi.org/10.1038/s41514-02200085-y

• 2. Saad, L., Zwiller, J., Kalsbeek, A., & Anglard, P. (2021). Epigenetic Regulation of Circadia Clocks and Its Involvement in Drug Addiction. Genes, 12(8). https://doi.org/10.3390/genes12081263

Presenting Author: Declan Douglas

Supervisor: Dr Carsten Skarke

AAV8-PCSK9 INDUCED HYPERCHOLESTEROLAEMIA AND ATHEROSCLEROSIS IN MUCOSAL MAST CELL COX-2 DEFICIENT MICE

Walley D¹, Tang SY^2,3,4, Lordan R^2,3,4, Das U^2,3,4, Joshi R^2,3,4, Skarke C^2,3,4, FitzGerald GA^2,3,4

¹UCD School of Medicine, University College Dublin, Ireland

²Perelman School of Medicine, Institute for Translational Medicine and Therapeutics, Philadelphia, USA

³Institute for Translational Medicine and Therapeutics (ITMAT), University of Pennsylvania Perelman School of Medicine, Philadelphia, USA

⁴Perelman School of Medicine, Department of Medicine, University of Pennsylvania, Philadelphia, USA

Non-steroidal anti-inflammatory drugs (NSAIDs) selective for cyclooxygenase-2 (COX-2) carry cardiovascular risks. Mast cells contribute to atherosclerosis by accumulating in perivascular tissue. We investigated the effect of COX-2 deletion (KO) in mucosal mast cells (MMCKO) to determine their role in atherosclerotic burden (AB) in a hypercholesterolaemic murine model.

Chm Cre^±/COX-2 FF mice were generated as MMCKOs and Cre-negative littermates used as controls. Hypercholesterolaemia was induced using retro-orbital administration of AAV8/Pcsk9 and feeding mice (n = 12) a western diet (WD) for 12 weeks. Non-invasive tail-cuff system or radio-telemetry was used to measure blood pressure (BP), heart rate (HR) and physical activity (PA). Aortae were stained using Sudan-IV and AB was determined by en-face analysis. Liver RNA was extracted and relative gene expression assessed by RT-qPCR. Systemic prostanoid biosynthesis was determined by mass spectrometry. Plasma glucose, LDL, HDL and triglycerides were measured using biochemical assays.

AAV8/Pcsk9 elevated PCSK9 expression and induced hypercholesterolaemia. Urinary prostanoid metabolite profile displayed sex and genotype differences. AB was greater in males; however, no significant differences were observed between controls and KOs in both sexes. BP, HR and PA were not significantly altered. Plasma HDL and LDL levels were significantly elevated after feeding WD but not glucose and triglyceride levels.

A larger cohort of mice is needed to be fed WD for longer durations. Higher or additional doses of AAV8/Pcsk9 may be administered to maintain hypercholesterolaemia. Increased understanding of the role of COX-2 in mucosal mast cells in atherosclerosis may help attenuate the risks of chronic NSAID administration.

Acknowledgement:

The authors would like to acknowledge the support of the University College Dublin Dean’s Scholarship.

Presenting Author: David Walley

Supervisor: Prof. Garret A. FitzGerald

Co-Supervisor:Dr Soon Yew Tang

PROFILES OF PAEDIATRIC PATIENTS RECEIVING PALLIATIVE CARE AT HOSPICE AFRICA UGANDA

Vaughan S¹, Kamate A²

¹UCD School of Medicine, University College Dublin, Ireland

²Hospice Africa Uganda, Mbarara, Uganda

The need for paediatric palliative care (PPC) is greatest in low-income countries where the paediatric population is large and resources scarce.¹ Where services exist, PPC research is limited. This study documents PPC patient profiles at Hospice Africa Uganda (HAU), aiming to increase understanding of this cohort, facilitating tailored care.

In this retrospective cross-sectional study, the number of children (< 18 years) enrolled at HAU’s Kampala site from 2016–2022 (N = 335) was obtained from the data registry. Data was extracted from the files of these patients and descriptive statistics were used to summarize variables of interest, using cases with available data for each variable. Missing data ranged from 0.0%-43.1% across summarized variables.

The paediatric patient proportion was 9.6%. 50.8% were male. The mean age was 9.7 ± 4.8 years. 87.7% had cancer, 2.2% HIV, 1.2% cancer and HIV and 8.9% ‘other’ (non-cancer, non-HIV). Of the ‘others’, sickle cell disease (65.5%) and cerebral palsy (10.3%) were predominant. 85.9% of patients presented with pain, of which 88.6% were prescribed morphine. Common symptoms (in > 15%) were swellings, wounds and decreased appetite. Main distresses (patient vs carer) were symptoms (74.9%, 50.7%), disease progression (17.4%, 42.0%), psychological distresses (15.4%, 9.8%) and financial constraints (4.1%, 23.4%). Patient care goals included symptom control (45.1%), curative treatment (36.5%), psychological (9.8%) and financial (8.6%) support. To date, 57.8% of patients have died, 36.6% lost-to-follow-up, 1.2% discharged and 4.3% remain in care.

This study provides insight into demographic, clinical and psychosocial characteristics of HAU’s paediatric patients, which can inform care, helping to meet patient needs.

References:

• 1. Downing J, Boucher S, Daniels A, Nkosi B. Paediatric palliative care in resource-poor countries. Children. 2018;5(2):27.

Acknowledgement:

This project was supported financially by a Dean’s Scholarship from UCD School of Medicine

Presenting Author: Sally Vaughan

Supervisor: Dr Agasha Doreen Birungi

PROFILES OF NON-CANCER AND NON-HIV PATIENTS RECEIVING PALLIATIVE CARE AT HOSPICE AFRICA UGANDA

Andrews Paterson M¹, Mwebesa E²

¹UCD School of Medicine, University College Dublin, Ireland

²Hospice Africa Uganda, Kampala, Uganda

Hospice Africa Uganda (HAU) was established in 1993 as a pioneer organization to offer culturally sensitive palliative care to Ugandans.¹ Since HAU’s establishment, antiretroviral therapy was introduced to combat the human immunodeficiency virus (HIV) epidemic, and unhealthy lifestyles were globalized.² As a result, Uganda has experienced an epidemiological transition; this emerging demographic has not yet been detailed by research. Through a retrospective cross-sectional study, a profile of patients without HIV and cancer was created. Pertinent parameters were collected from 100 patient files between the years 2017 and 2022 then analysed to obtain descriptive statistics. During the time frame, 1153 patients were enrolled for three or more months, and 100 (9%) patients were void of HIV and cancer. The majority of this group were female (n = 69; 69%). Age at enrollment ranged from 2 to 96 years with a mean of 50 years. Notable, the average age for females (59 years) was found to be older than males (39 years). The most common diagnosis was sickle cell disease, which afflicted 30 (30%) patients. The other most prevalent diagnoses were hypertension (n = 17; 17%), degenerative disc disease (n = 16; 16%), and arthritis (n = 15; 15%). Pain was common in nearly all (n = 93; 93%) patients. Among the 91 patients who scored their pain, 55 (60%) reported it to be severe or overwhelming, and a substantial 52 (95%) were prescribed oral liquid morphine for pain relief. The description of the outlined demographic can be used to inform decisions during the development of Uganda’s palliative care system.

Acknowledgement:

The author would like to acknowledge funding and support from the University College Dublin Dean’s SSRA International Summer Research Scholarship.

References:

• 1. Hospice Africa Uganda [Internet]. Hospice-africa.org. 2023 [cited 16 July 2023]. Available from: https://www.hospice-africa.org/

• 2. World Health Organization. Noncommunicable diseases [Internet]. World Health Organization; 2023 [cited 16 July 2023]. Available from: https://www.who.int/health-topics/noncommunicable-diseases#tab=tab_1

Presenting Author: Madelaine Andrews Paterson

Supervisor: Dr Eddie Mwebesa

REASONS FOR REFERRAL, MAIN DISTRESS, AND GOALS OF CARE: AN ANALYSIS COMPARING HIV/AIDS AND CANCER PATIENTS AT HOSPICE AFRICA UGANDA

Soares I¹, Natuhwera G²

¹UCD School of Medicine, University College Dublin, Ireland

²Clinical Department, Hospice Africa Uganda, Kampala, Uganda

Given that cancer and HIV/AIDS have different trajectories since antiretroviral therapy (ART) became widely available, these patients may differ in their care needs¹. The main objective of this study was to identify and compare cancer and HIV/AIDS patients’ reasons for referral, main distresses’ and goals of care.

The cross-sectional study retrospectively used a researcher-designed data abstraction instrument which collected data from 100 randomly selected case notes of 50 cancer and 50 HIV/AIDS patients. A Chi-Square (χ²) test was used for data analysis when comparing reasons for referral, main distress and goals of care between cancer and HIV/AIDS patients. All analyses were two-sided, and a p-value < 0.05 was considered statistically significant.

The primary reason for referral was pain and symptom control among cancer (96%) and HIV/AIDS patients (76%). The primary distress was unrelieved pain (56%) among both patient groups. The primary goal of care was pain and symptom control among cancer (82%) and HIV/AIDS patients (84%). There was a low positive correlation between diagnosis and main distress (r = 0.09, p < 0.000), diagnosis and goals of care (r = 0.15, p < 0.002) and a low negative correlation between diagnosis and reason for referral (r = -0.27, p < 0.002).

The study demonstrates pain is a prevalent concern among reasons for medical consultation, source of distress and care goals among HIV/AIDS and cancer patients at HAU. Clinicians may use these findings to improve individualized holistic care planning to optimize patients’ quality of life.

Acknowledgement:

The author would like to acknowledge an SSRA Dean’s Scholarship from the Medicine International Office.

Reference:

• 1. Ikwaras Okware S. Review of social challenges of heterosexual transmission of HIV/AIDS in Uganda. AIDS Updates - Recent Advances and New Perspectives. 2021.

Presenting Author: Isabella Soares

Supervisor: Dr Germans Natuhwera

THE CHANGES IN PROFILES AND PATTERNS OF CANCER AMONG PAEDIATRIC PATIENTS AT HAU

Tiernan G¹, Buyinza N²

¹UCD School of Medicine, University College Dublin, Ireland

²Hospice Africa Uganda, Kampala, Uganda

Hospice Africa Uganda (HAU) aims to provide ‘palliative care for all those in need in Africa’.¹ The purpose of this study was to identify the most common cancers presenting in paediatric patients between 2013–2022, to document the treatments received and profile the patient cohort to determine changes in trends and the implications of this.

This was a retrospective assessment of all accessible case files (428) of paediatric cancer patients that presented to HAU in the study period. Data was extracted from case files and recorded in a data collection tool. Descriptive statistics were calculated and formed the basis of analysis.

Table 1 Three most common cancer diagnoses in paediatric patients who presented to HAU 2013–2022

Between 41 and 56 patients presented annually, except for 2020/2021 (8 patients), reflecting the COVID-19 Pandemic.² ALL and Rhabdomyosarcoma were amongst the most common diagnoses in most years. Since 2017, Osteosarcoma prevalence increased; the most common diagnosis (26%) in 2022. Chemotherapy alone remains the most common treatment received. A large proportion of patients had not received/ un-recorded cancer treatments due to financial constraint, lack of accessibility/support. Sex, age and tribe across the cohort showed no significant changes. Morphine was prescribed to 62–88% of patients across the decade.

The main implications of this study include the need to improve record keeping, in particular HIV status and the requirement for further study of specific palliative care needs for patients with ALL, Rhabdomyosarcoma and Osteosarcoma. Additionally, improved patient education regarding side effects and complications of chemotherapy would benefit these patients.

Acknowledgements:

The author would like to acknowledge funding from the SSRA Dean’s Scholarship Program and friendly support and inspiration from Dr Nasur Buyinza, staff and patients at HAU.

References:

• 1. Where we started [Internet]. Hospital Africa Uganda: [cited 2023 Aug 3]. Available from: https://www.hospice-africa.org/where-we-started/

• 2. Uganda: WHO Coronavirus disease (Covid-19) dashboard with vaccination data [Internet]. World Health Organization; [cited 2023 Jul 31]. Available from: https://covid19.who.int/region/afro/country/ug

Presenting Author: Grace Tiernan

Supervisor: Dr Nasur Buyinza

CHARACTERIZATION OF NOVEL ACTIVATORS OF THE TRPMB CHANNEL IN SCHISTOSOMES

Petrow I¹, Park SK², Kumar S², Sprague D², Marchant J²

¹UCD School of Medicine, University College Dublin, Ireland

²Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, USA

Schistosomiasis is a disease caused by parasitic flatworms that afflicts millions of people across the globe. Infection causes severe complications such as liver enlargement, kidney damage, and bladder cancer [1]. The clinical treatment for schistosomiasis is a drug called Praziquantel (PZQ). PZQ works by activating an ion channel in the transient receptor potential melastatin subfamily named TRPM_PZQ. TRPM_PZQ activation by PZQ causes muscle contraction and worm paralysis [1]. However, certain strains of liver flukes (Fasciola spp,) are resistant to PZQ [1]. Therefore, it is important to scrutinize other ion channels which could serve as chemotherapeutic targets. One such ion channel is TRPM_B, another member of the same ion channel subfamily. The aim of this research project was to test the effect of several drugs on TRPM_B as a new target for treating schistosomiasis. This was done by confocal Ca²⁺ imaging to monitor the activation of TRPM_B. Cultured U2OS cells were treated with DMSO, various putative TRPM_B activators (MK1 through MK7, 10μM final concentration) and ATP (100μM as a positive control). Drugs that activate TRPM_B will cause calcium entry into the cell that is then reflected as an increased fluorescence of the fluorescent reporter dye, fluo-4. Image analysis was then done using Metamorph to quantify the increase in fluorescence intensity within individual cells. Several drugs (MK1 and MK3) were shown to robustly activate TRPM_B, while others (MK2, MK4, MK6, and MK7) had no effect. The structure–activity relationships of these drugs are under investigation. The results implicate several activators of TRPM_B as a potential target for therapeutic development.

References:

• 1. Park SK, Friedrich L, Yahya NA, Rohr CM, Chulkov EG, Maillard D, et al. Mechanism of praziquantel action at a parasitic flatworm ion channel. Science Translational Medicine. 2021 Dec 22;13(625).

Presenting Author:Ian Petrow

Supervisor:Dr Jonathan Marchant

AN ASSESSMENT OF PATIENT BARRIERS TO SEXUAL HEALTH CARE AND THEIR SOCIAL DETERMINANTS OF HEALTH

Fahy M¹, Weingarten L², Kolenchery N², Reno H³

¹UCD School of Medicine, University College Dublin, Ireland

²St. Louis County Department of Public Health, St. Louis Missouri, USA

³Washington University School of Medicine, Washington University in St. Louis Missouri, USA

The United States is experiencing a rising trend in sexually transmitted infections (STIs), prompting investigations into STI prevention¹. Healthcare providers are recognising the importance of social determinants of health (SDOH) in providing holistic services². Measuring and monitoring patient experience is needed to address barriers to STI prevention. This study aimed to design a survey to assess patient barriers to sexual health care and evaluate patient satisfaction with the healthcare services provided by the County Sexual Health Clinic, St. Louis, Missouri.

This study involved a quantitative survey of patients who presented to the clinic for a clinician visit. The SDOH patient survey was designed to assess demographics, sexual orientation and gender identity, and social determinants of health.

During the study period, 87 patients completed the survey. Patients who identified as male and female were equally likely to indicate they had the support of friends and family to visit the clinic (p = 0.49). Patients who identified as male reported less stress during a clinic visit (p = 0.05). There was no significant difference between patients who identified as male or female and had difficulty making time for the clinic visit (p = 0.38).

To reduce the rates of STIs, it is necessary to have targeted interventions aimed at social factors that impact specific populations. Stress is significantly more challenging for patients who identify as women. Further studies should examine the nature of the visit to understand the factors contributing to stress, offer resources, and improve care.

Acknowledgement:

The author would like to acknowledge the guidance by Hilary Reno MD, PhD and appreciates the opportunity and time provided. The authors would like to acknowledge the support of the University College Dublin Dean’s Scholarship and the Mark and Cathleen Reifsteck Scholarship.

References:

• 1. Centres for Disease Control and Prevention. THE U.S. STI epidemic showed no signs of slowing in 2021-cases continued to escalate [Internet]. 2023 Apr 11 [cited 2023 Aug 2]. Centres for Disease Control and Prevention. Available from: https://www.cdc.gov/media/releases/2023/s0411-sti.html#print

• 2. Andermann A, CLEAR Collaboration. Taking action on the social determinants of health in clinical practice: a framework for health professionals. CMAJ: Canadian Medical Association journal = journal de I ‘Association medicale Canadienne. 2016;188(17–18):E474-E483. https://doi.org/10.1503/cmaj.160177.

Presenting Author: Maeve Fahy

Supervisor: Dr Hilary Reno

EVALUATING THE SUSTAINABILITY OF THE EARLY WARNING SCORE INTERVENTION IN GLOBAL PEDIATRIC ONCOLOGY SETTINGS

O’Hagan J¹, Zabotka L², Carothers B³, Agulnik A⁴, Malone S²

¹UCD School of Medicine, University College Dublin, Ireland

²Department of Public Health, Washington University, St. Louis, U.S.A

³Center for Public Health Systems Science, Washington University, St. Louis, U.S.A

⁴Global Pediatric Medicine Department, St. Jude Children's Research Hospital, Memphis, TN, U.S.A

This study assesses the Pediatric Early Warning Score (PEWS) system's communication quality and sustainability in hospitals of varying resources. It aims to understand the link between communication (Critical Communication Survey (CritCom)) and PEWS perceived sustainability (Clinical Sustainability Assessment Tool (CSAT)), and how individual factors influence this relationship.

A cross-sectional survey was implemented across 12 hospitals using PEWS. Data were collected from 905 responses, with 599 for CSAT and 306 for CritCom. Spearman Rank Correlation and Mann Whitney U tests were used for statistical analysis.

The participants comprised 448 nurses and 383 doctors. Median scores for CSAT and CritCom were 4.28 and 4.11 out of 5, respectively. Results showed a weak correlation between CSAT and CritCom scores (rho = 0.294, p = 0.354). The quality care importance of PEWS and scientific evidence supporting PEWS both showed strong positive correlations with CSAT (rho = 0.79, p = 0.003; rho = 0.67, p = 0.02). A significant divergence was seen in evidence strength between nurses and doctors, with the Mann–Whitney U test (p = 0.002204, W = 18.5).

The results revealed patterns between communication and sustainability, with CritCom's "Empowerment" vs CSAT and CSAT's "Workflow Integration" vs CritCom being positively linked. Importantly, there's a strong consensus on the value of PEWS for quality care and the robustness of its supporting scientific evidence. However, a discernible difference in perspectives on the strength of this evidence exists between nurses and doctors. Future research will investigate these patterns further and seek to validate findings with a broader sample size.

Acknowledgment:

The author would like to acknowledge funding from the Dean’s scholarship at the University College Dublin.

References:

• 1. Agulnik, A., et al. Validation of a pediatric early warning system for hospitalized pediatric oncology patients in a resource-limited setting. Cancer. 2017;123(24):4903–4913.

• 2. Agulnik, A., et al. Reliability and validity of a Spanish-language measure assessing clinical capacity to sustain Paediatric Early Warning Systems (PEWS) in resource-limited hospitals. BMJ open. 2021;11(10):e053116.

Presenting Author: Justin O’Hagan

Supervisor: Dr Sara Malone

COMPARISON OF FAMILY PHYSICIAN REMUNERATION MODELS IN BRITISH COLUMBIA AND THEIR IMPACT ON HEALTHCARE GOALS

Budhwar R¹, Narayan S², Klimas J², McCracken R²

¹UCD School of Medicine, University College Dublin, Ireland

²Department of Family Practice, University of British Columbia, Vancouver, BC, Canada

British Columbia (BC) has implemented several different models for family physician remuneration to balance family physician shortages while attempting to achieve healthcare system goals. However, the key strengths and weaknesses of these models have not been fully characterized. This rapid policy analysis sought to describe and compare the main characteristics of all remuneration models for Family Physicians practicing in BC.

Published contracts, policy agreements, and other grey literature sources were used to examine current family physician remuneration methods (PRM). A structured worksheet was used to organize relevant data including income and benefits, paneling requirements, rules for employment, and assessment of advantages and disadvantages of a model.

A total of 8 remuneration models were identified. PRMs were then assigned to one of five groups and plotted along a variability spectrum. Variable and Dynamic Blended groups were found to be associated with higher quantities of care, greater patient acceptance, increased professional autonomy, and high patient satisfaction. Stable Blended, Fixed Interval and Fixed groups were associated with increased appropriate care in the first visit, high income stability and risk aversion, increased provider collaboration, and more likely to provide preventive care. Explicit incentives to increase patient health outcomes was found only in Variable and Stable Blended groups.

While there was significant diversity in the PRMs present in BC, there was limited research on the impact of care and patient outcomes related to each model. This analysis offers a baseline snapshot of the BC Family PRMs that can serve for future evaluations other Canadian provinces.

Acknowledgment:

The author would like to acknowledge funding from UCD School of Medicine Dean’s scholarships.

Presenting Author: Radha Budhwar

Supervisor: Dr Jano Klimas

Co-Supervisor: Dr Rita McCracken

VALIDATION OF A PREDICTION MODEL FOR THE DEVELOPMENT OF LIVER DISEASE IN CYSTIC FIBROSIS PATIENTS

Pollack I¹, Fitzpatrick E², Rowland M^{1, 3}, Galligan M³

¹UCD School of Medicine, University College Dublin, Ireland

²University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania, USA

³Children’s Health Ireland, Crumlin, Dublin, Ireland

Currently, there is no validated tool which can predict the development of liver disease in CF. Siegel et al. reported an algorithm based on age, log(GPR), and liver echogenicity to calculate the probability of progression to advanced CFLD.¹ We sought to validate this tool in a large national prospective database of PWCF over a 10 year period.

The Irish Longitudinal Study of CFLD (ILSCFLD) prospectively enrolled 95% of children with CF in Ireland in 2007. PWCF were evaluated at 5, 10 and, 15 year intervals for presence of CFLD and related complications. 10 year follow up data was used to validate the chosen prediction model.

443 PWCF were enrolled in 2007. 205 were excluded due to the pre-existing presence of liver disease or insufficient biomarker/ultrasound data to analyze at baseline. At 10 year follow up, 13 patients had developed CFLD, 133 patients had no evidence of liver disease, and 92 had nonspecific liver disease. A ROC curve was developed to test the prediction model using the ILSCFLD 2007 data. This demonstrated an area under the curve (AUC) of 0.7303 with a 95% CI of 0.5744–0.8661. Using the Youden index the threshold was determined to be 0.0867 with a specificity of 0.8444 and sensitivity of 0.5385.

At 10 year follow up, this real-world validation demonstrated that the sensitivity and specificity of the algorithm showed promise for prediction of CFLD. Insufficient data collection was an issue. Further modification and validation of this algorithm is needed to predict risk at different time points.

Reference:

• 1. Siegel MJ, Leung DH, Molleston JP, Ye W, Paranjape SM, Freeman AJ, et al. Heterogeneous Liver on Heterogeneous liver on research ultrasound identifies children with cystic fibrosis at high risk of advanced liver disease. Journal of Cystic Fibrosis, 2023; 2023;18:47

Presenting Author: Ian Pollack

Supervisor: Assoc Prof Emer Fitzpatrick

TRACKING THE SPATIOTEMPORAL RESPONSE OF MICROGLIA AND MACROPHAGES AFTER SPINAL CORD INJURY (SCI)

Hyde E¹, Colbert R², Walsh C², Reynolds J², Dooley D²

¹UCD School of Medicine, University College Dublin, Ireland

²UCD Conway Institute of Biomedical and Biomolecular Research, University College Dublin, Ireland

Spinal cord injury (SCI) is a complex medical challenge without a curative therapy. The pathophysiology involves a primary phase – physical damage from the mechanical lesion – which is followed and exacerbated by a secondary inflammatory phase. This secondary phase is driven by an influx of peripheral immune cells (largely macrophages) and activation of CNS-resident microglia. These immune cells have the potential to have beneficial or detrimental effects on injury progression, depending on their activation state. However, discriminating between macrophages and microglia is challenging, particularly in a traumatic environment.

This project aims to assess the spatiotemporal response of these two immune cell populations after SCI, using a novel genetic tool combined with immunohistochemistry. Hexb-tdTomato mice express fluorescent tdTomato (tdT) in microglia, allowing selective labelling of microglia. Through epifluorescence microscopy, the expression of tdT and F4/80 (a macrophage marker) was assessed in injured Hexb spinal cord tissue, up to 28 days post-injury (DPI).

No significant difference was found between the number of F4/80⁺ and tdT⁺ cells at any selected timepoint within or outside the lesion. However, a significant increase in both F4/80⁺ and tdT⁺ cells was observed at lesion sites between 3 and 4 DPI. From 4 DPI onwards, both immune cell populations were significantly higher in lesion versus non-lesion sites.

These results suggest that microglia are primarily driving the inflammatory response to SCI, with peripheral macrophages contributing insignificantly to the total number of F4/80⁺ cells. Furthermore, the period of 3 to 4 DPI may mark a critical timepoint for therapeutic intervention post-injury.

Presenting Author: Eoghan Hyde

Supervisor: Dr Dearbhaile Dooley

SEX-SPECIFIC ASSOCIATIONS OF PRENATAL PATERNAL CARDIOVASCULAR RISK SCORE AND OBESITY DEVELOPMENT IN SCHOOL-AGED CHILDREN: THE CHILD COHORT STUDY

Dempsey K¹, Rossi A², Jenkins D², Campisi S³, Azad MB⁴, Simons E⁴, Mandhane P⁵, Turvey S⁶, Moraes T³, Subbarao P^3,7,8, Miliku K^2,7

¹UCD School of Medicine, University College Dublin, Ireland

²Department of Nutritional Sciences, University of Toronto, Toronto, Canada

³Department of Pediatrics, The Hospital for Sick Children, Translational Medicine Program, Toronto, Canada

⁴Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada

⁵Department of Pediatrics, University of Alberta, Edmonton, Canada

⁶Department of Pediatrics, BC Children’s Hospital, University of British Columbia, Vancouver, Canada

⁷Department of Medicine, McMaster University, Hamilton, Canada

⁸Department of Physiology, University of Toronto, Toronto, Canada

Early-life exposures may influence cardiovascular (CVD) risk development in children in a sex-specific manner. While the role of maternal factors on child obesity is well-studied, the impact of paternal health and lifestyle is widely unexplored. This project aims to determine the associations between prenatal paternal CVD risk score and offspring BMI and obesity in school-aged children.

Using data from 1930 father-mother–child trios from the longitudinal Canadian CHILD Cohort Study¹, fathers were scored using a modified Interheart Cardiovascular Risk Score² (ICVRS) based on assessments obtained at the study enrollment visit (18 weeks gestation). The ICVRS included paternal age, anthropometric measures, health and behavioural choices. Offspring’s BMI WHO z-scores were derived at age five; z-scores > 1 were defined as overweight/obese. Sex-stratified multivariable linear analysis accounted for paternal education, ethnicity, breastfeeding exclusivity, parity, and screen time at age five. Maternal BMI categories were considered an effect modifier.

Median and 95% range of paternal ICVRS was 5.0 (0–14). At age five, 20% of children were overweight/obese. In male offspring, each unit increase in paternal ICVRS was associated with a 0.02 (95% CI 0.01, 0.04) higher BMI z-score. This association was stronger (0.05; 95% CI 0.02, 0.08) among overweight/obese mothers. In addition, in males with overweight/obese mothers but not females, paternal ICVRS was associated with aOR of 1.10 (95% CI 1.03, 1.16).

Our study is the first indicating an association of paternal CVD risk and childhood obesity development. These findings will inform future studies focused on preconception paternal risk factors and offspring health.

References:

• 1. Subbarao P, Anand SS, Becker AB, Befus AD, Brauer M, Brook JR, et al. The Canadian Healthy Infant Longitudinal Development (CHILD) Study: examining developmental origins of allergy and asthma. Thorax. 2015; 70(10): 998–1000.

• 2. McGorrian C, Yusuf A, Islam S, Jung H, Rangarajan S, Avezum A, et al. Estimating modifiable coronary heart disease risk in multiple regions of the world: the INTERHEART Modifiable Risk Score. Eur Heart J. 2011; 32(5): 581–589.

Presenting Author: Kendra Dempsey

Supervisor: Assistant Prof Kozeta Miliku

EXPLORING THE RELATIONSHIP BETWEEN TREATMENT MODALITY AND COMORBIDITY IN PATIENTS WITH CHRONIC KIDNEY DISEASE TREATED WITH KIDNEY REPLACEMENT THERAPIES

M. Ayibiowu^1,2, I. Mucsi¹

¹UCD School of Medicine, University College Dublin, Dublin, Ireland

²Ajmera Transplant Centre, University Health Network, Toronto, Canada

Chronic kidney disease (CKD) is a leading cause of morbidity and mortality worldwide.¹ Most patients with CKD also have other chronic conditions.² This analysis aims to determine the association between co-morbidity burden and kidney replacement treatment modality.

A cross sectional sample of patients on dialysis, kidney (KT) and kidney-pancreas (KP) transplant recipients completed the Charlson Comorbidity Index (CCI). Sociodemographic and clinical data was also collected. Transplant recipients were recruited from Toronto General Hospital, patients on dialysis from multiple dialysis units in Toronto. The association between treatment modality and CCI score was determined using an adjusted linear regression model and binary logistic regression.

Of the 1,573 participants (682 on dialysis, 732 KT and 159 KP) the mean (SD) age was 56(15) years; 40% were female. The association between treatment modality and CCI score was significant even after adjusting for age, sex, and ethnicity in the linear regression model. KP recipients had a higher CCI score than those on dialysis ($\beta =0.8, p<0.001, 95\% CI:0.5, 1.0$) while KT recipients had a lower CCI ($\beta =-0.5, p<0.001, 95\% CI: -0.7, -0.3$). Binary logistic regression also confirmed that KP recipients were more likely (OR, 8.12 [95% CI, 4.0–16.0]), while KT recipients were less likely (OR, 0.63 [95% CI, 0.50–0.81]) to have moderate-severe comorbidity burden when compared to patients on dialysis.

Our results confirmed that KP recipients have higher comorbidity burden while KT recipients have lower comorbidity burden than patients on dialysis. Further studies should assess the impact of comorbidities on quality of life, symptom burden and clinical outcomes.

References:

• 1. Mucsi I, Ekundayo O, Tang E, et al. Validation of PROMIS CATs in Kidney Transplant Recipients (KTR) - preliminary results PROMIS Health Organization Conference. Dublin, Ireland 2018.

• 2. MacRae C, Mercer SW, Guthrie B, Henderson D. Comorbidity in chronic kidney disease: a large cross-sectional study of prevalence in Scottish primary care. British Journal of General Practice. 2021;71(704):e243-e9.

Presenting Author: Mowa Ayibiowu

Supervisor: Dr Istvan Mucsi

UNRAVELLING THE MOLECULAR EFFECTS OF A NOVEL LEUKAEMIA-RELATED GENE FUSION

Grady E¹, Biswas S^1,2, Dias T^1,2, McCarthy P^1,2,3, Trinquand A³, Betts D³, Malone A³, Bond J^1,2,3

¹UCD School of Medicine, University College Dublin, Ireland

²Systems Biology Ireland, University College Dublin, Dublin, Ireland

³Children’s Health Ireland, Crumlin, Dublin, Ireland

B-cell acute lymphoblastic leukaemia (B-ALL) is the most common childhood malignancy. It is characterised by the uncontrolled proliferation of immature B-lymphoid cells in the bone marrow and blood. While patient outcomes are generally good, with > 90% survival, current treatment regimens require identification of known genetic abnormalities [1]. These act as prognostic that help dictate treatment intensity. TCF3 fusions have been proved to be hallmarks of B-ALL development with their partner gene highly influencing prognosis [2]. Therefore, identifying new partners of TCF3 fusions and understanding their effects is essential to better B-ALL treatment in the future.

Here we describe the novel TCF3:PIK3R1 fusion identified in a paediatric patient that presented at Crumlin with Pre B-ALL. Molecular and cytogenetic studies revealed the presence of the transcript in the cells, allowing us to design an expression vector containing the fusion sequence.

We used this vector to lentivirally transduce a cell line to express the TCF:PIK3R1 fusion, allowing us to analyse its effects on signalling pathways and function. Using Western blots, a decrease in the AKT signalling pathway was noted, in line with altered PIK3R1 activity. We also saw increases in anti-apoptotic molecules, such as BCL2. Cell cycle analysis showed very little change between control cells and fusion containing cells.

Considering this increase, Venetoclax, a BCL2 inhibitor, was used to investigate potential therapies for leukaemia containing TCF3:PIK3R1. Preliminary results suggest that fusion-expressing cells are more sensitive to this agent.

Our findings, together with the outcome of the patient, suggest that TCF3:PIK3R1 does not generate an aggressive form of B-ALL.

Acknowledgement:

The author would like to acknowledge funding from the University College Dublin Ad Astra Academy.

References:

• 1. Huang, F.L., et al., Pathogenesis of pediatric B-cell acute lymphoblastic leukemia: Molecular pathways and disease treatments. Oncol Lett, 2020. 20(1): p. 448–454.

• 2. Salim, M., et al., Cryptic TCF3 fusions in childhood leukemia: Detection by RNA sequencing. Genes Chromosomes Cancer, 2022. 61(1): p. 22–26.

Presenting Author: Emma Grady

Supervisor: Prof Jonathan Bond

Co-Supervisor: Dr Sharmila Biswas

ANALYSING MOLECULAR DATA TO IDENTIFY TREATMENT AVENUES IN ACUTE MYELOID LEUKAEMIA

Parkinson-Coombs N¹, Tudose C²

¹UCD School of Medicine, University College Dublin, Ireland

²Systems Biology Ireland, University College Dublin, Dublin, Ireland

To study acute myeloid leukaemia (AML) and its treatment, cell lines are used as in vitro models for drug testing. In order for drug testing to yield clinically actionable results, these cell lines must accurately resemble the tumour they claim to represent. We addressed this issue through computational analysis of RNA-sequencing data and drug screen results from AML cell lines obtained from the Cancer Cell Line Encylopaedia (CCLE) and patient samples from the BEAT-AML dataset.

We applied NMF (Non-Negative Matrix Factorisation) to CCLE transcriptional data of AML cell lines. NMF provided us with three distinct transcriptional clusters correlating to either the French-American-British (FAB) classification (stage of haematological differentiation arrest), or the presence of a KMT2A rearrangement. These clusters showed strong correlation with transcriptional profiles from patient samples in the BEAT-AML dataset, which themselves corresponded to FAB classification. In line with our predictions, NB4, an acute promyelocytic leukaemia cell line which expresses a PML-RARA translocation, displayed a strong correlation with M3 patient samples (Pearson’s R = 0.6). Additionally, some cell lines (i.e., HDMYZ) correlated poorly with all patient samples, indicating misclassification as AML.

Drug screen analysis revealed significant differences in sensitivity profiles between NMF-defined clusters. Navitoclax, a BLC2 inhibitor, was more effective in cluster one as compared to cluster three (p-value = 0.0087).

In summary, the use of computational approaches allows the selection of cell lines which are more representative of leukaemia samples from patients, and therefore selection of better treatment targets.

Presenting Author: Nuala Parkinson-Coombs

Supervisor: Prof Jonathan Bond

DIAGNOSTIC ACCURACY OF POOLING SAMPLES TO DETECT N. GONORRHOEAE AND C. TRACHOMATIS USING THE CEPHEID XPERT ® CTNG ASSAY

Shanley A¹, O Sullivan L², Lynch M², Broderick A²

¹UCD School of Medicine, University College Dublin, Ireland

²Microbiology Department, Mater Misericordiae University Hospital, Dublin, Ireland

STI screening is one of the core strategies for the prevention of STIs. Nucleic acid amplification testing is the gold standard for the detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG); however, it is also significantly more expensive than traditional culture methods. The aim of this study is to evaluate the performance of specimen pooling and to determine the viability of this approach to STI testing in a tertiary hospital.

Using the Xpert ® CT/NG assay, 204 patient samples were tested for CT and NG. Following routine analysis, pooled specimens were created using samples from two sites from the same patient and reanalysed. A further 5 external quality assessment samples were pooled and reanalysed, with an overall total of 107 pooled samples. Results obtained using pooled specimens were compared to individual site testing and agreement was assessed as categorical agreement.

107 pooled tests were conducted. The CT positive and negative predictive values were 100% and 98.6%, respectively. The NG positive and negative predictive values were 100% and 96.7%, respectively. Pooled specimen testing failed to detect 1 CT and 2 NG infections that were positive by individual testing.

Two-site pooled CT and NG testing has a similar performance to single anatomical site testing. Pooling samples has potential as a method for detection of CT/NG, with a small reduction in sensitivity. Cost savings of up to 50% may be achieved by implementing the pooled testing strategy.

Presenting Author: Amy Shanley

Supervisor: Dr Andrea Broderick

PARASITE CONTROL ON IRISH FARMS AS PART OF THE TARGETED ADVISORY SERVICE ON ANIMAL HEALTH

Alostath M¹, De Waal T², Meunier N³

¹UCD School of Medicine, University College Dublin, Ireland

²UCD School of Veterinary Medicine, University College Dublin, Ireland

³The Archways, Carrick-on-Shannon, Leitrim, Ireland

Parasites pose a significant threat to livestock productivity, animal welfare, and economic sustainability in farming. The necessity for effective parasite control is especially acute in Ireland, where agriculture plays a pivotal role in the economy. This study aims to analyze the current veterinary recommendations for parasite control in Irish sheep farms.

Utilizing extensive on-farm survey data from Animal Health Ireland (AHI), this observational study conducted a comprehensive secondary data analysis. The dataset included 1237 sheep farms and 3711 veterinary recommendations. Basic descriptive statistics were employed for the analysis, and the data were categorized to reveal patterns in the types of advice given.

Veterinary recommendations were found to be diverse, covering nine primary categories including Fecal Egg Count (FEC), treatment advice, quarantine protocols, and accurate dosing, among others. The prominence of FEC and accurate dosing suggests a strong emphasis on diagnostic accuracy and effective treatment, respectively. The data revealed a tailored, farm-specific approach in veterinary advice, showing significant regional variations in recommendations. The findings indicate a strong alignment between current veterinary practices and recognized best practices in parasitological management. Emphasis on diagnostic accuracy, tailored treatment plans, and biosecurity measures underscore the effectiveness of the current advisory framework.

Veterinarians in Ireland appear to be well-aligned with best practices in parasitic control, employing a nuanced, context-sensitive approach in their recommendations. The study affirms the role of veterinary guidance in enhancing the sustainability of Irish farming, although further research could explore the impact of these practices on specific health markers in sheep.

Presenting Author: Mohammad Alostath

Supervisor: Prof Theo de Waal

EVALUATION OF THE NEW, HYBRID BASIC LIFE SUPPORT TRAINING MODEL AT UNITY HEALTH TORONTO

Badross M¹, Allan K², Beavers L³, Brydges R⁴, Dewar-Morgan C³, Fraser K³, Hajjar N⁵, Khodadoust N⁴, Lin S⁶, Wong N⁵

¹UCD School of Medicine, University College Dublin, Ireland

²Divison of Cardiology, St. Michael’s Hospital a sit of Unity Health Toronto, Toronto, Canada

³Simulation Program, Unity Health Toronto, Toronto, Canada

⁴Technology-enabled Education, Unity Health Toronto, Toronto, Canada

⁵Division of Critical Care, St. Michael’s Hospital, Toronto, Canada

⁶Division of Emergency Medicine, St. Michael’s Hospital, Toronto, Canada

Around 290,000 in-hospital cardiac arrests (IHCA) occur annually in the United States, however, survival rates remain low.¹ High quality cardiopulmonary resuscitation (CPR) and early defibrillation is vital for survival. Nevertheless, CPR delivered by first responders is often poor², indicating the need for better basic life support (BLS) training. We aim to demonstrate that a new, hybrid BLS training model at a large academic hospital was non-inferior to the previous 2 h in-class model.

To evaluate the efficacy of the new training model, CPR metrics (mean rate, depth and compression fraction) were collected from staff attending the old (2010–2013) and new (2022–2024) models for BLS training. CPR metrics from real IHCAs, following the implementation of each model, were also collected. Descriptive statistics were used for data analysis.

Between 2010–2013 and November 2022 to July 2023, we collected CPR metrics from 790 and 90 first responders, respectively. Both the mean CPR rate (104.2 compressions/minute old BLS vs. 112.2 compressions/minute new BLS, p < 0.001) and depth (2.27 inches old BLS vs. 2.54 inches new BLS, p < 0.001) remained within recommended CPR guidelines. In contrast, the mean CPR fraction improved significantly (62.1% old BLS vs. 89.9% new BLS, p < 0.001) following the new BLS program. The IHCA data showed similar trends (see Table 1).

We observed that a new, hybrid BLS training model is equally effective as an in-class training model, when training first responders how to respond to IHCAs.

Table 1

CPR metrics collected from IHCA

Acknowledgement:

The author wishes to acknowledge that this project is funded by Academic Health Science Center Alternative Funding Plan.

References:

• 1. Andersen LW, Holmberg MJ, Berg KM, Donnino MW, Granfeldt A. In-Hospital cardiac arrest. JAMA [Internet]. 2019 Mar 26;321(12):1200. Available from: https://doi.org/10.1001/jama.2019.1696

• 2. Everett-Thomas R, Yero-Aguayo M, Valdes B, Valdes G, Shekhter I, Rosen LF, et al. An assessment of CPR skills using simulation: Are first responders prepared to save lives? Nurse Education in Practice [Internet]. 2016 Jul 1;19:58–62. Available from: https://doi.org/10.1016/j.nepr.2016.05.003

Presenting Author: Miriam Badross

Supervisor: Dr Steve Lin

Co-supervisor: Dr Katherine Allan

ENHANCED PLATELET ACTIVATION IN PATIENTS WITH NEWLY DIAGNOSED MYELOPROLIFERATIVE NEOPLASMS

Kasianenko D^1,2,3, Kelliher S^1,2,3, Bashkara A⁴, Ní Áinle F^1,2,3,5,6, Maguire PB^1,7,8, Kevane B^1,2,3,6

¹Conway SPHERE Research Group, UCD Conway Institute of Biomedical and Biomolecular Research, University College Dublin, Ireland

²UCD School of Medicine, University College Dublin, Ireland

³Department of Haematology, Mater Misericordiae University Hospital, Ireland

⁴University of Texas, School of Medicine, Dallas, TX, USA

⁵Department of Haematology, Rotunda Hospital, Dublin, Ireland

⁶Irish Network for Venous Thromboembolism Research (INViTE), Dublin, Ireland

⁷School of Biomedical and Biomolecular Science, University College Dublin, Ireland

⁸UCD Institute for Discovery, University College Dublin, Dublin, Ireland

Myeloproliferative neoplasms (MPNs) are chronic bone marrow malignancies driven by somatic mutations leading to constitutively activated JAK-STAT signalling and cell proliferation. Thrombosis, including both arterial events and venous thromboembolism, is the leading cause of morbidity and excess mortality. Thrombocytosis is a hallmark of MPN, however the precise contribution of platelets to hypercoagulability remains to be fully elucidated.

Following ethical approval and informed consent, 21 patients with MPN and 18 controls with reactive thrombocytosis were enrolled. ELISAs were used to determine platelet activation markers in plasma. Platelet poor plasma was isolated from whole blood by centrifugation at 3,000 g for 10 min and stored at -80 °C. Sandwich ELISAs for P-selectin, platelet factor 4 (PF4), and thrombospondin 1 (R&D Systems, Minneapolis, MN) were performed according to the manufacturer’s instructions. All standards and samples were assayed in duplicate. Statistical analysis was performed using R.

Plasma expression of P-selectin was significantly increased in patients with MPN (94.9 ± 66.2 (pg/mL) in MPN v 34.5 ± 11.4(pg/mL) in controls; P = 0.00057). Interestingly, platelet a-granule protein thrombospondin was increased (707.7 ± 376.1 (pg/mL) in MPN v 397.5 ± 296.6 (pg/mL) in controls; P = 0.015). No difference was observed in PF4 concentrations. (247.3 ± 136.1 (pg/mL) in MPN v 296.6 ± 166.4 (pg/mL) in controls; P = 0.42).

Here we demonstrate evidence of enhanced platelet hyperactivity in the plasma of patients with newly diagnosed MPN compared to controls. We plan to conduct untargeted proteomic analysis of platelet lysate and platelet releasate from these patients to further characterise the platelet profile and its contribution to the clinical hypercoagulable phenotype.

Presenting Author: Dmytro Kasianenko

Supervisor: Dr Barry Kevane

Co-supervisor: Dr Sarah Kelliher

THE IMPLICATIONS OF ARTIFICIAL INTELLIGENCE (AI) FOR DIGITAL HEALTH AND SOCIAL CARE IN IRELAND

O’Neill I¹, Burke E²

¹UCD School of Medicine, University College Dublin, Ireland

²Health Information and Quality Authority, Cork, Ireland

Artificial intelligence (AI) has the potential to revolutionise digital health and social care in Ireland, but despite its favourable position technologically Ireland does not have a clear strategy for AI inclusion in healthcare. Therefore, this narrative literature review examines the implications of AI in Irish healthcare, addressing its potential contributions, risks, and the need for policy options to mitigate these risks. This study utilized a narrative literature review approach, covering and critically evaluating sources including scientific articles, meta analyses, books, guidelines, governance proposals, and AI studies. The results of this study show that AI has the potential to address key challenges faced by the Irish healthcare system like chronic diseases and emergency department pressures posed by the ageing population. Limitations and risks of AI are also discussed, including algorithm errors, liability complications, and reinforcement of healthcare disparities. Implications of this study include the need for policy recommendations such as end-user involvement throughout AI development, informed selection of data, and the need for diverse perspectives; examples of steps and strategies other countries are taking to further AI adoption are also included in this review.

Presenting Author: Ivan O’Neil

Supervisor: Dr Emma Bourke

SODIUM-GLUCOSE COTRANSPORTER-2 INHIBITORS AND SYNTHETIC LIPOXIN MIMETICS AS REGULATORS OF EPITHELIAL INTEGRITY AND FIBROSIS

Bonner R¹, Gaffney A² Moore D², Godson C²

¹UCD School of Medicine, University College Dublin, Ireland

²UCD Diabetes Complications Research Centre, UCD Conway Institute of Biomedical and Biomolecular Research, University College Dublin, Ireland

Diabetic kidney disease is a progressive disorder which can lead to fibrosis and eventual organ failure. Intriguingly, although the sodium-glucose cotransporter-2 inhibitors (SGLT-2i) were introduced in clinical practice to regulate hyperglycemia in diabetes it is now proposed that the beneficial effects of these agents on the kidney and cardiovascular system are independent of glucose lowering and they exert pleiotropic responses including regulating renal epithelial cell integrity. Separately, the therapeutic potential of synthetic lipoxin mimetics as anti-inflammatory agents in a murine model of diabetic kidney disease have been demonstrated [1].

My project investigated how SGLT-2i may attenuate responses in immortalised human proximal tubule cells exposed to fibrotic conditions. The aim of this research was to (a) investigate the potential of the SGLT-2i dapagliflozin to protect epithelial integrity and (b) examine potential methods to further augment the renoprotective and cardioprotective benefits associated with this class of drug.

HK-2 cells were subcultured and exposed to profibrotic stimulus TGF-β1 2.5ng/ml in the presence and absence of prototypic SGLT-2i dapagliflozin 500 nM and a synthetic lipoxin mimetic AT-01-KG 1 nM for forty eight hours. Alterations of gene expression and marker proteins were examined to look at any phenotypic switches in response to TGF-β1 and any impact of dapagliflozin, AT-01-KG or combinations thereof.

Although robust and reproducible assays for gene expression and protein levels were established we did not observe the anticipated response to TGF-β1 as has been previously reported by numerous investigators [2] so it was not possible to assess the impact of dapagliflozin and of AT-01-KG. We conclude that the TGF-β1stock was not biologically active.

Acknowledgment:

The author would like to acknowledge funding from Science Foundation Ireland.

Reference:

• 1. Brennan EP, Mohan M, McClelland A, Tikellis C, Ziemann M, Kaspi A, et al. Lipoxins Regulate the Early Growth Response–1 Network and Reverse Diabetic Kidney Disease. Journal of the American Society of Nephrology. 2018 Feb 28;29(5):1437–48. 2.

• 2. Brennan EP, Nolan KA, Börgeson E, Gough OS, McEvoy CM, Docherty NG, et al. Lipoxins attenuate renal fibrosis by inducing let-7c and suppressing TGFβR1. Journal of the American Society of Nephrology: JASN [Internet]. 2013 Mar 1 [cited 2022 Nov 22];24(4):627–37. Available from: https://pubmed.ncbi.nlm.nih.gov/23520204/

Presenting Author: Rachel Bonner

Supervisor: Prof Catherine Godson

Co-Supervisor: Dr Dean Moore

EVALUATING THE EFFECT OF MULTI—DISCIPLINARY TEAM (MDT) MEETINGS FOR SPINE ONCOLOGICAL PATIENT MANAGEMENT

Jain N¹, Morris S²

¹UCD School of Medicine, University College Dublin, Ireland

²National Spinal Injuries Unit, Mater Misericordiae University Hospital, Dublin, Ireland

The treatment of spinal metastases is complex and requires the consideration of multiple factors, including tumour radiosensitivity, extent of spinal compression, presence of impaired cord function, and the patient’s overall health and likely prognosis.¹ In 2018, the National Spinal Injuries Unit (NSIU) introduced Multi - Disciplinary Team (MDT) meetings with input from various disciplines including spinal surgeons, radiation oncologists and medical oncologists to support decision making for patients with spinal tumors. Before 2018, the spinal consultant on call took these decisions. This study aims to evaluate this practice and explore its outcomes.

Two consecutive patient cohorts of 100 patients were identified prior to and following implementation of MDT meetings. Data was collected from records maintained for MDT meetings and patient charts from the electronic data system used by the NSIU. An anonymised study database with key metrics including demographics, clinical management pathway and clinical outcomes for both cohorts was generated.

It was observed that data across both cohorts for most of the metrics was inconsistently available due to incomplete patient records. One metric which had data consistently available was patient ages. An unpaired two-tailed t-test was conducted which yielded no statistically significant difference in patient ages between cohorts (p = 0.252).

These results demonstrate that there has been no significant change in the demographics of patients with spinal metastases treated by the NSIU after the implementation of MDTs. In order to make deductions regarding additional metrics, more complete patient records must be maintained and further research must be conducted.

Reference:

• 1. Delank K-S, Wendtner C, Eich HT, Eysel P. The treatment of spinal metastases. Dtsch Arztebl Int [Internet]. 2011 [cited 2023 May 25];108(5):71–9; quiz 80. Available from: https://doi.org/10.3238/arztebl.2011.0071

Presenting Author:Noyonika Jain

Supervisor: Prof Seamus Morris

INVESTIGATION INTO THE SIGNIFICANCE OF TICK BORNE FEVER-RELATED COMORBIDITIES IN IRISH SHEEP FLOCKS

McDermott C¹, Gilmore J², McGettrick S³, Froehlich R³, Flaherty AM³, Ó’Muireagáin C³, Harte C³, Fagan S⁴, Sheehan M⁵, O’Shaughnessey J⁶, Mee J⁷, Keady T.W.J.⁸, Zintl A¹

¹UCD School of Veterinary Medicine, University College Dublin, Ireland

²Farmlab Diagnostics, Emlagh Lodge Veterinary Centre, Elphin, Roscommon, Ireland

³Sligo Regional Veterinary Laboratory, Fawcett’s Bridge, Doonally, Sligo, Ireland

⁴Athlone Regional Veterinary Laboratory, Coosan, Athlone, Westmeath, Ireland

⁵Kilkenny Regional Veterinary Laboratory, Leggatsrath, Hebron Road, Kilkenny, Ireland

⁶Central Veterinary Research Laboratory, Backweston, Cellbridge, Kildare, Ireland

⁷Teagasc, Animal and Bioscience Department, Moorepark Research Centre, Fermoy, Cork, Ireland

⁸Teagasc, Animal and Grassland Research and Innovation Centre, Athenry, Galway, Ireland

Tick borne fever (TBF) is a tick-transmitted disease in ruminants caused by the Gram-negative bacterium Anaplasma phagocytophilum. Clinical signs include pyrexia, depression, immunosuppression and increased susceptibility to diseases such as Louping Ill and pasteurellosis¹. This study aimed to investigate comorbidities that were typically associated with TBF in lambs from different age groups and locations throughout Ireland.

The study included lamb carcasses under one year of age submitted to Athlone, Kilkenny, and Sligo Department of Agriculture, Food and the Marine Regional Veterinary Laboratories between 1st January 2021 and 31st December 2022. Aborted foetuses were excluded. Spleen samples were tested for the presence of A. phagocytophilum using qPCR and grouped into positive and negative categories. Clinical histories and postmortem findings were retrieved from the Laboratory Information Management System (LIMS) and collated onto a Microsoft Excel Worksheet following an anonymisation process. Comorbidities of positive tests determined by veterinarians from post-mortem and laboratory findings were classed by pathogen, aetiology and organ system affected.

Out of a total of 871 submissions, 54 were positive for TBF (6.2%). Pneumonia was diagnosed in 24% of positive cases, where Mannheimia haemolytica was the primary agent in 75% of these pneumonias. Pneumonia was diagnosed in 13.7% of negative cases, with M. haemolytica isolated in 43.6% of pneumonias. In a previous survey of ovine mortality in Ireland in 2016, pneumonia was diagnosed in 10.5% of lambs, with M. haemolytica isolated in 30.8% of pneumonias.²

These results indicate that infection with TBF may have a positive association with pathogen susceptibility.

Acknowledgement:

The author would like to acknowledge funding from the Department of Agriculture, Food and the Marine.

References:

• 1. Øverås J, Lund A, Ulvund MJ, Waldeland H. Tick-borne fever as a possible predisposing factor in septicaemic pasteurellosis in lambs. Veterinary Record. 1993;133(16).

• 2. Murray GM, Fagan S, Murphy D, Fagan J, Ó Muireagáin C, Froehlich R. Descriptive analysis of ovine mortality in sentinel sheep flocks in Ireland. VetRecord. 2019;184(21):649–649

Presenting Author: Ciara McDermott

Supervisor: Assoc Prof Annetta Zintl

Co-Supervisor: Dr Shane McGettrick

CLINICAL PROFILE OF PAEDIATRIC PATIENTS WITH 22Q11.2 DELETION SYNDROME ATTENDING CHILDREN’S HEALTH IRELAND AT CRUMLIN: A RETROSPECTIVE STUDY

Soobratty HF¹, Mulcahy W², Gadancheva V³, Kelleher S², McNicholas F^1,3

¹UCD School of Medicine, University College Dublin, Ireland

²Department of General Paediatrics, Children’s Health Ireland. Crumlin, Dublin, Ireland

³Department of Psychiatry, Children’s Health Ireland,Crumlin, Dublin, Ireland

22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion syndrome with a prevalence of 1 in 2000 to 1 in 4000 live births. The presentation of this multisystemic condition is exceptionally diverse leading to patients navigating through a myriad of clinical specialties. This study aims to map the clinical profile of children with 22q11.2DS attending a designated 22q11.2DS clinic in a paediatric hospital in Ireland.

Clinical data was extracted retrospectively from the Integrated Patient Management System and files of patients who attended the clinic between October 2017 and June 2023. Data was collated on Microsoft Excel and statistical analysis was performed using IBM SPSS v.27.

196 patient records were reviewed. The cohort consisted of 52.0%(n = 102) male and a mean age of 11.4 years. 94.9%(n = 186) had 22q11.2 typical deletion, 4.1%(n = 8) duplication, 0.5%(n = 1) distal deletion and 0.5%(n = 1) complex genetics rearrangement. 14.2%(n = 28) of the cases were familial. Patients attended an average of six specialties since birth, with cardiology having the highest number of patients for active follow-up(36.7%, n = 72). 46.9%(n = 92) were referred to child psychiatry. The most common diagnoses were palatal abnormalities(56.6%, n = 111) and cardiac defects(56.1%, n = 110). Allied health professionals were involved in the care of 49.4%(n = 97) patients. Sleep disturbances were also noted(23.0%, n = 45), with 10.2%(n = 20) taking melatonin medication. 30.6%(n = 60) had established social communication difficulties and 18.9%(n = 37) had available IQ assessment reports of intellectual disability.

The clinical profile of 22q11.2DS patients is complex and their holistic care is challenging. The integrated clinic ensures follow-up by relevant services for both screening and symptomatic management.

Presenting author: Hayfa Fatima Soobratty

Supervisors: Prof Fiona McNicholas & Dr Suzanne Kelleher

Co-supervisor: Dr Veselina Gadancheva

THE EFFECTS OF PROGESTERONE AND MITOQ ON SPERM FERTILIZING ABILITY USING THE BOVINE AS A MODEL

Rambo R¹, Koelle S¹

¹UCD School of Medicine, University College Dublin, Ireland

Mitochondria are cellular organelles responsible for producing energy in the form of adenosine triphosphate (ATP) through oxidative phosphorylation. During this process, reactive oxygen species (ROS), also known as free radicals, are produced as natural byproducts. ROS play a crucial role in cellular signaling and regulation. However, an imbalance between ROS production and antioxidant defense mechanisms can lead to oxidative stress, causing damage to cellular structures, including proteins, lipids, and DNA¹.

Sperm metabolism and energy production naturally generate reactive oxygen species (ROS) in mitochondria. Some ROS is necessary for normal sperm function, acting as signaling molecules. However, excessive ROS production leads to oxidative stress, damaging sperm DNA, proteins, and lipids, impairing motility, viability, and fertilization capacity². Sperm possess intrinsic antioxidant defense mechanisms to counterbalance harmful ROS effects. Therefore, Antioxidant supplementation has been studied as a potential treatment to improve sperm quality in men with infertility issues related to oxidative stress^1,2.

The study aims to investigate the effects of supplements and hormones on sperm survival time, motility, and fertilizing ability during freezing and thawing processes. Unlike previous studies that focused on the effects of supplements before freezing, this research will assess the protective effects of Mitoquinone (200 nM) and progesterone (10 nM) shortly after thawing using bovine as a model. A new sperm analyzer machine from Dyneval, in addition to a unique digital live cell imaging system was used, which mimics conditions near the tubal sperm reservoir in vivo.

Progesterone and MitoQ will be examined to understand their impact on sperm characteristics. By analyzing sperm behavior under these conditions, the study seeks to identify new approaches for safeguarding and enhancing sperm quality during freezing and thawing. These findings are particularly valuable for preserving sperm from young individuals, such as cancer patients, individuals with diseases, or sex-sorted sperm from livestock. Additionally, the insights gained from this research can lead to advancements in assisted reproductive technologies like artificial insemination (AI) and in vitro fertilization (IVF) for both humans and animals.

References:

• 1. Tiwari S, Mohanty TK, Bhakat M, Kumar N, Baithalu RK, Nath S, et al. Comparative evidence support better antioxidant efficacy of mitochondrial-targeted (Mitoquinone) than cytosolic (Resveratrol) antioxidant in improving in-vitro sperm functions of cryopreserved buffalo (Bubalus bubalis) semen. Cryobiology. 2021 Aug;101:125–34.

• 2. Wu C, Dai J, Zhang S, Sun L, Liu Y, Zhang D. Effect of Thawing Rates and Antioxidants on Semen Cryopreservation in Hu Sheep. Biopreservation and Biobanking. 2021 Jun 1;19(3):204–9

Presenting Author: Reem Rambo

Supervisor: Prof Sabine Koelle

DEMOGRAPHICS OF SPINAL SURGERY PATIENTS AT THE BEACON HOSPITAL AND ASSOCIATED SURGICAL RISK FACTORS

Cheong SHX¹, Pierce A², Morris S^3,4

¹UCD School of Medicine, University College Dublin, Ireland

²Beacon Hospital Research Institute, Beacon Hospital, Sandyford, Dublin, Ireland

³National Spine Institute, Sandyford, Dublin, Ireland

⁴Beacon Centre for Orthopaedics, Sandyford, Dublin, Ireland

Wear and tear changes in the spine from arthritis often result in spinal stenosis. Surgical interventions such as discectomy, decompression, and/or fusion surgery are often the last resort to alleviate pain. Dural tears are a common complication of spinal surgery and can lead to cerebrospinal fluid (CSF) leak, CSF fistula formation, and pseudomeningocele.

The aim of the research in the hospital was to (a) identify the demographics of patients undergoing spinal surgery and (b) review the risks and complications associated with spinal procedures. This was completed via retrospective medical chart review and compared against the outcomes of an online literature review.

For the literature review, there were a total of 15 papers included. As for the audit, from 01/01/2023 until 31/05/2023 there were 65 patients undergoing spinal surgery. One dural tear complication was noted. The rate of dural tear at Beacon is 1.5% while the rate from the literature reviewed was 1.9%.The five risk factors identified through the literature review include age, body mass index, smoking, revision surgery, and segments covered. Age and revision surgery are significant risk factors for dural tears. The odds of sustaining a dural tear increase by 2.7% per year of life. [1] Patients undergoing revision surgery are twice as likely to suffer a dural tear as those undergoing primary surgery [2].

The results demonstrate that age and revision surgery are significant risk factors of dural tear. Limitations of the study were the timeframe and chart number reviewed. Future projects could compare outcomes with a national spine registry.

References:

• 1. Strömqvist F, Jönsson B, Strömqvist B, Swedish Society of Spinal Surgeons. Dural lesions in decompression for lumbar spinal stenosis: incidence, risk factors and effect on outcome. European Spine Journal. 2012 May;21:825–8.

• 2. Milton, R., Kalanjiyam, G.P., Rajasekaran, S., Shetty, A.P. and Kanna, R.M., 2023. Dural injury following elective spine surgery–A prospective analysis of risk factors, management and complications. Journal of Clinical Orthopaedics and Trauma, p.102172.

Presenting Author: Sumitra Hui Xian Cheong

Supervisor: Mr Anthony Pierce

ANALYSIS OF HUMAN RIGHTS & VULNERABLE GROUP INCLUSION IN THE MALAYSIAN MENTAL HEALTH POLICY AND STRATEGY: CONTENT ANALYSIS USING EQUIFRAME

Vandaiyar K¹, Mannan H²

¹UCD School of Medicine, University College Dublin, Ireland

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

In the past decade, Malaysia's health system has progressed through policy reforms, yet lacks comprehensive incorporation of rights and inclusivity dimensions. Prioritizing vulnerable populations' rights in mental health policies and aligning human rights principles with public health strategies can enhance population health.

Using the EquiFrame framework, we analyzed Malaysia's National Mental Health Strategic Plan 2020–2025 and the Psychiatric and Mental Health Services Operational Policy. We adapted the framework to Malaysia's mental health landscape, then used NVivo-12 to code the two policy documents for 22 core concepts and 16 vulnerable groups. We analyzed for core concept presence, vulnerable group coverage, and core concept quality ratings—the latter reflecting the extent to which policies stated a policy action or intention to monitor that action—yielding an overall summary ranking.

The National Mental Health Strategic Plan 2020–2025 covered 68% of core concepts and 44% of vulnerable groups, achieving a 59% quality rating. The Psychiatric and Mental Health Services Operational Policy addressed 77% of core concepts and 19% of vulnerable groups, with a 55% quality rating. Both policies attained a moderate overall ranking, though vulnerable group coverage was < 50% with migrant, refugee, and gender diverse communities entirely absent. Quality ratings indicate insufficient inclusion of actions or monitoring intentions for several core concepts.

Our study highlights the need for more inclusive and rights-based mental health policies in Malaysia. Neglecting human rights and vulnerability hinders fair service access and compromises quality, with crucial implications for achieving mental health equity in the country.

Presenting Author: Kavessh Vandaiyar

Supervisor: Assoc Prof Hasheem Mannan

SEX DIFFERENCES IN HIPPOCAMPAL SEX STEROIDS FOLLOWING NEONATAL HYPOXIA–ISCHEMIA

Isik I¹, Cetin F^2,3, Ozaydin B^2,4, Cagatay N^2,3, Yapici S^2,3, Collo L⁵, Goy RW⁵, Kapoor A⁵, Ferrazzano P^2,6, Levine JE^5,6, Cengiz P^2,3

¹UCD School of Medicine, University College Dublin, Ireland

²Waisman Center, University of Wisconsin-Madison, WI, USA

³Department of Pediatrics, University of Wisconsin-Madison, WI, USA

⁴Department of Neurological Surgery, University of Wisconsin-Madison, WI, USA

⁵Wisconsin National Primate Research Center, University of Wisconsin-Madison, WI, USA

⁶Department of Neuroscience, University of Wisconsin-Madison, WI, USA

Neonatal hypoxia–ischemia (HI) related encephalopathy is one of the major causes of learning and memory deficits in children. Clinical and experimental studies have shown that male newborns are two times more susceptible to the effects of HI, a phenomenon that is poorly understood. Our recent studies show that there is a sex difference in expression of the estrogen receptor alpha (ERα) which is upregulated in the female hippocampus following HI and confers sex-specific female-biased neuroprotection via neurotrophin receptor, tyrosine kinase B (1). The objective of this study is to determine sex hormone contents of the hippocampi following HI to investigate the availability of estradiol (E₂) as a ligand to ERα produced by local aromatization of testosterone (T).

Sham and HI surgeries were performed in postnatal day 9 C57BL/6 J male and female mice using Vannucci’s HI model. Hippocampi were dissected, weighted and frozen immediately 3 days post-HI. For E₂ and T content measurements, two hippocampi were pooled as n = 1 and homogenized. Hormones were extracted and analyzed using LC–MS/MS (2). ANOVA was used for statistical analysis.

Hippocampal E₂ (ng/g) contents were not significantly different between the experimental groups. Hippocampal T (ng/g) content was significantly higher in HI male IL (2.455 ± 0.5984, n:8) compared to HI female IL (0.8848 ± 0.7454, n:8) (p = 0.0377). Male hippocampal E₂ (ng/g) contents positively correlated with T contents (R² = 0.5174, p = 0.0017).

T content increases in male IL hippocampi and decreases in female IL hippocampi following HI. There is a sex difference in T levels in IL hippocampi following HI.

References:

• 1. Cikla U, Chanana V, Kintner DB, Udho E, Eickhoff J, Sun W, et al. ERalpha Signaling Is Required for TrkB-Mediated Hippocampal Neuroprotection in Female Neonatal Mice after Hypoxic Ischemic Encephalopathy(1,2,3). eNeuro. 2016; 3(1).

• 2. Kenealy BP, Kapoor A, Guerriero KA, Keen KL, Garcia JP, Kurian JR, et al. Neuroestradiol in the hypothalamus contributes to the regulation of gonadotropin releasing hormone release. J Neurosci. 2013; 33(49): 19051–19059.

Presenting Author: Irem Isik

Supervisor: Prof Pelin Cengiz

UNVEILING THE ROLE OF EXOSOMES IN CREATING AN IMMUNOSUPPRESSIVE MICROENVIRONMENT IN PATIENT-DERIVED GASTRIC CANCER ORGANOIDS

Donia R¹, Cornand D^2,3, Kim J^2,3, Williams T^2,3, Wickware J^2,3,4,5., Rayat G^2,3,4,5

¹UCD School of Medicine, University College Dublin, Ireland

²Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada

³Li Ka Shing Centre for Health Research Innovation, University of Alberta, Edmonton, Canada

⁴Ray Rajotte Surgical-Medical Research Institute, University of Alberta, Edmonton, Canada

⁵Alberta Transplant Institute, University of Alberta, Edmonton, Canada

Cancer-derived exosomes can modulate the tumor microenvironment by inducing apoptosis and changing the phenotype of immune cells (1, 2). This study aims to understand the key mechanisms of how exosomes influence the anti-cancer response of immune cells by creating an immunosuppressive microenvironment in gastric cancer patients.

To determine the effect of exosomes on immune cells, organoids will be cultured with exosome-depleted growth medium for 72 h at physiological conditions, then medium will be collected and analyzed. The amount and identity of exosomes will be determined by bicinchoninic acid assay kit, and their size and distribution will be visualized by transmission electron microscopy.

The exosome identity will be confirmed by determining the presence of exosome surface proteins (CD9, CD63, CD81), cytosolic proteins (HSP70, TSG101), and the endoplasmic reticulum protein calnexin using Western blot. Peripheral Blood Mononuclear Cells (PBMCs) will be incubated with or without exosomes at different concentrations (1, 10, and 100 μg/ml), and then collected and processed for flow cytometry, qRT-PCR, and enzyme-linked immunosorbent assay (ELISA). Statistical analyses will be performed using Kruskal–Wallis non-parametric analysis of variance with post hoc Dunn test.

This project is an initial and important step towards the development of personalized immune therapy for gastric cancer patients. The findings from this study will form the foundation of personalised gastric cancer research which will focus on further investigation of exosomes and their cargos as well as immune cells and immune molecules using RNA sequencing and proteomics methods.

Presenting author: Reem Donia

Supervisor: Prof Gina Rayat

EVALUATION OF A SCENARIO-BASED URGENT CARE COURSE FOR FINAL YEAR MEDICAL STUDENTS – A THEMATIC ANALYSIS OF GROUP INTERVIEWS IN THE PROFESSIONAL COMPLETION MODULE

Tham B¹, Broughan J¹, McCombe G¹, Cullen W¹, Breen N¹

¹UCD School of Medicine, University College Dublin, Ireland

There is a deficiency in procedural training during the transition from final year of medical education to the intern year.[1] Scenario-based learning has emerged as a solution to bridge the gap in students’ confidence and preparedness during this transition. [2] This qualitative study aimed to evaluate a two-day scenario-based urgent care course completed by final year students in the ‘Professional Completion Module (PCM)’ at the UCD School of Medicine.

Fifteen students participated in course evaluation focus groups, where they were encouraged to share views and experiences. Data was collected through three semi-structured focus group interviews, each conducted after a separate iteration of the course. Focus groups were audio-recorded, transcribed verbatim and analysed using Braun and Clarke’s Reflexive Thematic Analysis (RTA) approach. NVIVO software aided the qualitative analysis process.

The findings showed that all students reported an enjoyable learning experience and expressed increased confidence and application of practical skills. Five main themes emerged - ‘positive feedback’, ‘core opinions’, ‘suggestions’, ‘critique’ and ‘overall medicine course’. The themes highlighted overwhelming praise for the course, a desire for the course’s emphasis on ‘soft skills’ training (drawing bloods, oxygen, handling medical equipment) to be translated into the overall medical curriculum, and the implementation of more sessions like the two-day course throughout the overall curriculum.

This study reinforced the value of scenario-based learning for preparing students in transition from final year to intern year in medical training. The findings have implications for the implementation of scenario-based learning initiatives, overall medical course delivery, and medical training research.

References:

• 1. Al Ansari M, Al Bshabshe A, Al Otair H, Layqah L, Al-Roqi A, Masuadi E, et al. Knowledge and confidence of final-year medical students regarding critical care core-concepts, a comparison between problem-based learning and a traditional curriculum. Journal of Medical Education and Curricular Development. 2021;8:238212052199966. https://doi.org/10.1177/2382120521999669

• 2. Dusch M, Narciß E, Strohmer R, Schüttpelz-Brauns K. Competency-based learning in an ambulatory care setting: Implementation of simulation training in the Ambulatory Care Rotation during the final year of the MaReCuM model curriculum. GMS J Med Educ. 2018 Feb 15;35(1):Doc6. https://doi.org/10.3205/zma001153. PMID: 29497691; PMCID: PMC5827188.

Presenting Author: Bianca Tze Ee Tham

Supervisor: Assoc Prof Nick Breen

Co-Supervisors: Prof Walter Cullen & Mr John Broughan

EXPLORING THE THERAPEUTIC POTENTIAL OF PSYCHEDELIC AGENTS FOR THE TREATMENT OF DRUG ADDICTION

Beygi M^{1, 2}, Keegan L², Kelly Y², Murphy K²

¹UCD School of Medicine, University College Dublin, Ireland

²Neurotherapeutics Research Group, UCD Conway Institute of Biomedical and Biomolecular Research, University College Dublin, Ireland

Addiction is usually characterised by specific criteria such as: 1. Compulsion to use drugs, 2. Feelings of dysphoria without drugs, and 3. Inability to control drug intake⁽¹⁾. Cocaine, the most prominent psychostimulant, is also linked to intense dysphoria. Current therapies and pharmaceuticals for treating cocaine and psychostimulant addictions are inadequate, highlighting the potential of psychedelics as therapeutic agents. In recent years, research into the therapeutic benefits of psychedelics has grown, particularly for psychiatric conditions like post-traumatic stress disorder, anxiety and depression. To explore their potential as addiction treatments, we studied the effects of a range of psychedelics on cocaine addiction. Our study used in vivo shotgun mass spectrometry, in vitro immunocytochemistry and real time Polymerase Chain Reaction (PCR) to assess the therapeutic impact of these psychedelics on cocaine addiction. The results demonstrated a significant reversal of cocaine-mediated protein expression regulation in the brain following psychedelic treatment. However, our pathway analysis revealed little overlap in the proteins and biological pathways affected by each psychedelic in the brain. Remarkably, different psychedelics not only activated distinct pathways and proteins but also exhibited variation in specific brain structures in our study - the nucleus accumbens and hippocampus. These discrepancies could be attributed to factors like receptor affinity, drug interactions, and dosage. Future research should address these discrepancies to identify the most effective psychedelic as a therapeutic agent for addiction treatment. Understanding the unique mechanisms of each psychedelic can pave the way for improved therapies and better outcomes in combating addiction.

Acknowledgement:

The author would like to acknowledge the Neurotherapeutics Research Group at UCD Conway Institute for Biomolecular & Biomedical Research for the use of their facilities, equipment and their continuous support throughout this project.

Reference:

• 1. George F. Koob, Michael A. Arends, Mandy L. McCracken, Michel Lemoal. Introduction to Addiction [Internet]. Amsterdam: Elsevier Science Publishing Co Inc; 2019. Available from: https://doi.org/10.1016/B978-0-12-816863-9.00001-7

Presenting Author: Mani Beygi

Supervisor: Professor Keith Murphy

Co-Supervisors: Ms Louise Keegan & Mr Yazeed Kelly

MORNING STIFFNESS IS A WEAK MARKER OF INFLAMMATION IN AXIAL SPONDYLOARTHRITIS

Belanger C^{1, 2}, Chim T², Haroon N², Inman R D²

¹UCD School of Medicine, University College Dublin, Ireland

²Schroeder Arthritis Institute, Toronto Western Hospital, Toronto, Ontario, Canada

Axial Spondyloarthritis (AxSpA) is an inflammatory arthritis affecting the spine and peripheral joints¹. Blood tests including C-reactive proteins (CRP) and erythrocyte sedimentation rates (ESR) are elevated in 40% of patients. Morning stiffness is considered to correlate well with disease activity which is assessed using the patent-reported Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The aim was to examine the relationship between back stiffness (BASDAI questions 5 and 6 which examine duration and severity) and inflammation measurements (CRP and ESR) using retrospective data.

575 ankylosing spondylitis (AS) or non-radiographic axial spondyloarthritis (nr-AxSpA) patients with a 17.68-year average disease duration including 402 males having no biological drug use were studied, yielding 866 CRP and 862 ESR observations. Analysis was done using Pearson’s and Kendall’s rank correlation tests due to a lack of linearity in variables and univariable linear regression analysis to account for clustering.

Morning stiffness and the log of inflammatory measures were found to be relatively weak, with a less than 5% chance of an increase in inflammation measures for each BASDAI unit increase. Less than 3% of the change in CRP and ESR can be explained by a linear relationship with morning stiffness. A linear model cannot, therefore, explain 90% of the relationship.

The results demonstrate that the duration and severity of morning stiffness as measured by the BASDAI is a poor surrogate for inflammation and has little correlation with CRP and ESR rates within the body (r ranging from 0.11 to 0.17).

Reference:

• 1. Brigham and Women’s Hospital. Spondyloarthritis [Internet]. [cited 2023 Jul 24]. Available from: https://www.brighamandwomens.org/medicine/rheumatology-inflammation-immunity/services/spondyloarthritis#:~:text=Spondyloarthritis%20is%20a%20group%20of,Axial%20spondyloarthritis

Presenting Author: Carli Belanger

Supervisors: Dr Robert Inman & Dr Nigil Haroon

Co-supervisor: Dr Sinead Maguire

ANALYSIS OF THE SURGICAL INTERVENTION FOR COLORECTAL CANCER – A REVIEW OF CURRENT AVAILABLE LITERATURE

Jun W¹, Mannan H²

¹UCD School of Medicine, University College Dublin, Ireland

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

CRC (colorectal cancer) is one of the most prevalent cancers internationally as it is the 3rd most diagnosed cancer and the 2nd cancer caused mortality [1]. The current surgical intervention for CRC is laparoscopic surgery as numerous systematic reviews has highlighted its benefits over open surgery. However, robotic / robotic-assisted surgery is an upcoming field and its benefits are not fully compiled.

The aim of this study is to outline the outcomes of robotic surgery for CRC and compare it with laparoscopic surgery to understand whether it provides a significant clinical advantage to justify its feasibility in current practices.

All studies are pooled from PubMed, Google Scholar, and ClinicalTrials.gov. Based off the hierarchy of evidence, the primary studies interested in this review were RCTs (randomized controlled trials), however, some retrospective analysis were included if intervention and outcomes were relevant. The primary outcomes and secondary outcomes were tabled, and the confidence interval and P values of the primary outcome were also tabled. All P values < 0.05 are considered significant.

Results concluded that robotic surgery has couple of benefits over conventional laparoscopic surgery, such as post-operation complication where robotic = 13.2% (23/174) and laparoscopic = 23.7% (41/173); 95% CI -10.5 [-18.6 to -2.3]; p = 0.013, which is statistically significant [2]. Overall, it can be concluded that robotic surgery does has clinically significant advantage over conventional laparoscopic surgery.

References:

• 1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: a Cancer Journal for Clinicians. 2021 Feb 4;71(3):209–49.

• 2. Xu J, Tang W, Zhang Z, Wei Y, Ren L, Chang W, et al. Robotic versus laparoscopic abdominoperineal resections for low rectal cancer: A single‐center randomized controlled trial. Journal of Surgical Oncology. 2022 Aug 29;126(8):1481–93.

Presenting Author: Jun Xiang Wong

Supervisor: Assoc Prof Hasheem Mannan

DESIGNING A FRAILTY MORTALITY INDEX TO EVALUATE THE SURGICAL ELIGIBILITY OF GERIATRIC PATIENTS WITH TRAUMATIC SPINAL CORD INJURY

Barve A¹, Marland H², McDonnell J², Wall J², Darwish S², Butler J^1,2

¹UCD School of Medicine, University College Dublin, Ireland

²National Spinal Injuries Unit, Department of Trauma & Orthopaedic Surgery, Mater Misericordiae University Hospital, Dublin, Ireland

Traumatic spinal cord injuries (tSCI) amongst older patients (> 65 years) have increased in recent years. With an increasing life expectancy, there has also been an increase in the prevalence of underlying comorbidities. While current evidence suggests that emergency surgery within 24 h of injury greatly improves post-operative outcomes in all patients, anecdotal evidence has shown that some patients in the older adult age group benefit from conservative management. Due to the absence of a common consensus outlining the optimal treatment plan, this decision often varies. Hence, this study aims to create a grading index to assess patient eligibility for surgery based on demographical and clinical factors.

For this retrospective study, we will include patients above the age of 65 years old who presented to the National Spinal Injuries Unit with a tSCI from 2016 to 2023. All patient identifiers will be pseudonymized prior to analysis. The clinical outcomes of these patients will be reviewed using demographic details, fracture location, pre- and post-operative American Spinal Cord Injury Association (ASIA) grades, American Society of Anesthesiologists (ASA) grade, Modified 5-point Frailty Index, treatment strategy, time to surgery, length of operation, intra- and post-operative complications, number of patients requiring the high-dependency unit (HDU), HDU length of stay (LOS), number of patients requiring the intensive-care unit (ICU), ICU LOS, overall LOS and patient demise. Based on this data, statistical correlations between poor post-operative outcomes and underlying comorbidities will be explored. The data analysis will be done on R-studio, using the Chi-squared test, Fisher’s exact test and Pearson’s correlational analysis.

Since this study is ongoing, definite results have not been produced. However, it is hypothesized that patients of an older age group with a higher number of comorbidities would benefit from conservative management. Conversely, patients of a younger age group with a fewer number of comorbidities would benefit from surgical intervention.

Thus, this frailty mortality index would enable a more accurate method to categorize patients based on associated comorbidities. This would not only simplify the decision-making process, but also improve patient care.

Reference:

• 1. Jackson AB, Dijkers M, DeVivo MJ, Poczatek RB. A demographic profile of new traumatic spinal cord injuries: Change and stability over 30 years. Archives of Physical Medicine and Rehabilitation. 2004 Nov;85(11):1740–8. https://doi.org/10.1016/j.apmr.2004.04.035

• 2. Fehlings MG, Vaccaro A, Wilson JR, Singh A, W. Cadotte D, Harrop JS, et al. Early versus delayed decompression for traumatic cervical spinal cord injury: Results of the surgical timing in Acute Spinal Cord Injury Study (STASCIS). PLoS ONE. 2012 Feb 23;7(2). https://doi.org/10.1371/journal.pone.0032037

Presenting Author: Arnav Barve

Supervisor: Prof Joseph Butler

GENETIC ANALYSIS OF A MURINE CROHN’S DISEASE MODEL

Yau YS¹, Doogan K², Aljubury M², Stepanova M², Onn L², Aherne CM²

¹UCD School of Medicine, University College Dublin, Ireland

²UCD Conway Institute of Biomedical and Biomolecular Research, University College Dublin, Ireland

IBD including Crohn’s disease (CD) and ulcerative colitis (UC) are chronic, relapsing, intestinal diseases affecting increasing global populations. Current therapeutic strategies are only effective in 50% of patients leaving need for new therapies. Only a few models exist to study CD. Crohn’s-like ileitis is observed in the TNF^ΔARE mouse model due to high levels of tumour necrosis factor (TNF). Dr. Aherne’s group previously obtained differential expressed genes in TNF^ΔARE ileum compared to wildtype controls at pre, active and chronic phases of disease. This project aimed to analyse signalling pathways associated with genetic changes during these disease timepoints.

Ingenuity Pathway Analysis (IPA) was used to analyse signalling pathways. TNF treatment of mouse ileum organoids were used determine if TNF^ΔARE genetic changes could be studied in molecular detail.

Analysis of the top 40 altered genes in chronic disease identified a number of genes that are highly upregulated but are not yet associated with IBD. Further IPA analysis demonstrated the “Leucocyte Extravasation Pathway” as being enriched in active and chronic disease. This pathway contains multiple matrix metalloproteinase (MMP) genes which the Aherne lab recently identified to be involved in intestinal epithelial repair. TNF treatment of organoids determined that 10 ng/mL was the appropriate concentration to replicate the exposure of the epithelium to TNF in TNF^ΔARE mice.

Future studies will test the relevance of newly identified genes in CD. Furthermore, MMP gene expression will be measured in TNF-treated organoids to test the relevance of the genetic findings in the TNF^ΔARE model.

Presenting Author: Yong Sheng Yau

Supervisor: Dr Carol Aherne

PROSPECTIVE COMPARISON BETWEEN MANUAL CYTOLOGY EVALUATION AND AUTOMATED EVALUATION OF URINE BACTERIURIA IN DOGS

Lima M¹, Moulier D¹, Leornard F¹, Cuq B¹

¹UCD School of Medicine, University College Dublin, Ireland

Automated urinalysis is available now in veterinary medicine. The Idexx SediVue® has been used routinely in the companion animal hospital for urinalysis. However, can the presence of bacteria be directly interpreted from the machine results compared to the gold standard method of urine sediment cytology?

Comparison of an automated bacteriuria determination using the Idexx SediVue® compared to manual cytology in canine urine in order to determine the accuracy of the automated urinalysis.

Cytological evaluation of urine will be more accurate than automated urinalysis to detect bacteriuria in dogs.

Canine urine routinely submitted to the lab was included. Based on the semi quantitative results from the SediVue® 54 dogs with absent bacteria in their urine and 25 dogs with presence of bacteria according to the automate were enrolled over 8 weeks. Sediment was prepared and stained, and the slides were reviewed by the first author of this abstract for the presence or absence of bacteria.

Confusion matrix were established to determine the sensitivity, specificity, predictive positive and negative values as well as the accuracy of the SediVue compared to the manual cytology.

Table 1

Sensitivity, specificity, predictive positive and negative values as well as the accuracy of the SediVue compared to the manual cytology for bacteria, cocci and rods in canine urine

The Idexx SediVue® was determined to have moderate ability to detect bacteriuria overall. The automated analysis was excellent to determine the absence of cocci and had a good accuracy to detect the presence of rods. In the presence of sperm, automated evaluation will suspect or confirm the presence of rods.

Presenting Author: Miranda Lima

Supervisor: Dr Benoît Cuq

USING BROTH DILUTION METHODS TO EVALUATE THE ACCURACY OF THE AUTOMATED ANALYSER IDEXX SEDIVUE® IN DETECTING BACTERIURIA

Esim-Enoh E¹, Cuq B², Leonard F²

¹UCD School of Medicine, University College Dublin, Ireland

²UCD School of Veterinary Medicine, University College Dublin, Ireland

The SediVue® is used as a tool to diagnose bacteriuria with increasing frequency due to its easy-to-use nature and quick run times. Thus, it was necessary to test how accurate the machine is. The SediVue® was tested with known concentrations of various microorganisms commonly causing urinary tract infections in dogs to determine its limit of detection (LOD) and to discover the different parameters that affected detectability.

The LOD showed no notable differences between Gram positive or negative organisms but the SediVue® appeared to preferentially detect rods over cocci. Furthermore, results suggested that the ability of the SediVue to detect bacteria was improved in the presence of other urine constituents as the LOD of bacteria in broth was generally higher than that of bacteria in urine(Escherichia coli in urine could be detected at levels as low as 4.00 × 10³ CFU/ml [in a sample size of 20], whereas the lowest number of organisms detected in broth was 2.71 × 10⁶ CFU/ml [in a sample size of 6]).

Therefore, it was concluded that despite the small numbers of samples tested, the SediVue® could be a good qualitative tool for bacteriuria. It showed similar detection abilities for Gram-positive and Gram-negative organisms but did not differentiate well between rods and cocci. This is of clinical concern in terms of treatment options and prudent prescribing as treatments for Gram-positive cocci and Gram-negative rods may differ.

Presenting Author:Emile Esim-Enoh

Supervisor:Dr Benoit Cuq

Co-Supervisor:Dr Finola Leonard

REPURPOSING SLAUGHTERHOUSE WASTE: ASSESSING THE VIABILITY OF DECELLULARIZED BLOOD VESSELS

AlNaqbi S¹, Khan R², Corridon P²

¹UCD School of Medicine, University College Dublin, Ireland

²Department of Immunology and Physiology, College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates

Vascular decellularization has been deemed a potential source for vascular grafts which remedies transplant rejection. Decellularization is the process of removing cellular components from native tissue whilst maintaining the ECM, creating a biocompatible and non-immunogenic scaffold.¹

Sheep aortas and common brachiocephalic trunks were harvested from a slaughterhouse. These were then cleaned and sectioned into sections averaging 4 cm (n = 42). The vessels were then grouped into 7 and placed into 4 different solutions. These included 1%, 2%, and 4% zwitterionic surfactant (Ecover) solutions for 2 and 4 days, and 0.9% saline as control. Samples were placed on an orbital shaker and washed. Surface tension tests were performed to assess washing efficacy.

The data demonstrated a range in surface tensions (45.70–71.83 mN/m) with no correlation to concentration of surfactant (r = -0.487). Nanodrop spectrophotometry revealed a decrease in DNA yield of 1%2D and 2%4D samples compared to control (45.0% and 51.3% respectively). The 2%2D and 4%4D also showed a decrease (50.6% and 43.2% respectively), while the 2%4D and 4%4D samples had increased yield (7.10% and 53.9% respectively). Shear stress was emulated utilizing a peristaltic pump to assess structural integrity. The 1% solution vessels were tested using various physiological flow rates. The vessels were able to withstand their structure, however, the 1%2D samples showed better leakage control.

The findings suggest lower surfactant concentrations can obtain more effective and structurally stable decellularization. In addition, as evidenced by the high DNA yield, the washing protocol can be improved to ensure improved removal of surfactant remnants and cellular debris.

Reference:

• 1. Wang X, Chan V, Corridon PR. Decellularized blood vessel development: Current state-of-the-art and future directions. Frontiers in Bioengineering and Biotechnology. 2022 Aug 8;10.

Presenting Author: Shaikha AlNaqbi

Supervisor: Dr Peter R Corridon

INVESTIGATING THE CORRELATIONS AMONG BASELINE SERUM 25-HYDROXYVITAMIN D, CORRECTED CALCIUM, ALBUMIN AND PARATHYROID HORMONE IN PATIENTS WITH OSTEOPENIA/OSTEOPOROSIS

Labelle J¹, Shirriff K², Adachi JD³, Watts D⁴, Woo C⁴, Raza H⁴, Okwuegbuna K⁴, Mbuagbaw L³, Haaland D^2,3,5

¹UCD School of Medicine, University College Dublin, Ireland

²The Waterside Clinic, Barrie, Ontario, Canada

³McMaster University, Hamilton, Ontario, Canada

⁴Khure Health Inc, Toronto, Ontario, Canada

⁵Northern Ontario School of Medicine, Sudbury, Ontario, Canada

25-hydroxyvitamin D (25(OH)D) and parathyroid hormone (PTH) are regulators in calcium homeostasis and bone metabolism. The associations among them are of interest concerning patients with osteopenia/osteoporosis, as abnormalities in these parameters can impact bone health¹. This study explores correlations among serum 25(OH)D, corrected calcium, albumin and PTH in osteopenia/osteoporosis patients.

This retrospective chart review was conducted at The Waterside Clinic in Barrie, CA. Records were selected for 371 patients aged 50+ , with baseline serum 25(OH)D, and history of subcutaneous denosumab. Data extracted were demographics, laboratory results and bone mineral density values. Statistical tests included Pearson coefficient, one-way ANOVA, Bonferroni and chi-squared.

A variation in mean PTH across 25(OH)D tertiles was found (p = 0.01). The tertile with the lowest 25(OH)D had the highest PTH of 5.7 pmol/L compared to the middle tertile of 4.8 pmol/L and the highest 25(OH)D tertile with a PTH of 4.6 pmol/L. Likewise, the univariate analysis found a negative correlation (R = -0.172, p = 0.001) between PTH and 25(OH)D. Albumin and 25(OH)D demonstrated a positive relationship (R = 0.105, p = 0.05) in univariate analysis. No correlation was found between 25(OH)D and corrected calcium.

This study supports a negative correlation between PTH and 25(OH)D and positive correlation between albumin and 25(OH)D. The data suggest some patients with 25(OH)D values at the low end of normal likely suffer from low-grade secondary hyperparathyroidism despite “normal” PTH values. Thus, for particular parameters, reliance upon mean lab values with 95% confidence intervals derived from population statistics may not best support optimal health considerations within personalized medicine.

Acknowledgment:

Data collection and support using AI provided by Khure Health Inc.

Reference:

• 1. Laird E, Ward M, McSorley E, Strain JJ, Wallace J. Vitamin D and bone health: potential mechanisms. Nutrients. 2010 Jul;2(7):693-724

Presenting Author: Julia Labelle

Supervisor: Dr Derek Haaland

Co-Supervisor: Dr Karen Shirriff

THE ROLE OF CONTINUOUS GLUCOSE MONITORING IN NON-DIABETIC PREGNANCIES: A SCOPING REVIEW

Pomeroy L¹, Nazir SF², Kennelly MM², O’Higgins AC²

¹UCD School of Medicine, University College Dublin, Ireland

²UCD Centre for Human Reproduction, The Coombe Hospital, Dublin, Ireland

Continuous glucose monitoring (CGM) has emerged as a promising tool that offers valuable insights into glycaemic variability. Although routinely used in pregnancy for type 1 and type 2 diabetes mellitus, the utilisation of CGM in non-diabetic pregnancies is a relatively novel area of research. This scoping review aims to explore the existing literature that describes the use of CGM in non-diabetic pregnancies and to summarize its properties.

Five databases were searched for studies on CGM use in non-diabetic pregnancies. Identified articles were subject to a two-stage screening process followed by data extraction, according to the Joanna Briggs Institute methodology for scoping reviews.¹ Reviews and duplicate studies were removed. Thirty-four studies were included in the review. Data was collected based on glucose parameters, population, study design, and neonatal and maternal outcomes.

CGM has been researched in a heterogenous population of non-diabetic women at all stages of pregnancy, including intrapartum. Interpretation and reporting of CGM data across the studies were inconsistent, with fifty-two parameters employed to describe the data. Furthermore, definitions differed between the studies regarding the same metrics. There was an inconsistent approach among studies to the relationship of CGM data with clinical outcomes. Clinical outcomes were not reported in all studies and reported outcomes differed between studies with some reporting neonatal outcomes only, some maternal outcomes only and some reporting both.

Our study demonstrates a real need for standardisation in reporting of CGM data and its associated clinical outcomes in a pregnant population.

Reference:

• 1. Peters MDJ, Godfrey C, McInerney P, Munn Z, Tricco AC, Khalil, H. Chapter 11: Scoping Reviews (2020 version). In: Aromataris E, Munn Z (Editors). JBI Manual for Evidence Synthesis, JBI, 2020.

Presenting Author: Lynne Pomeroy

Supervisor: Assoc Prof Amy O'Higgins

Co-Supervisor: Assoc Prof Mairead Kennelly

EXPLORING INTERPRETATION OF CONTINUOUS GLUCOSE MONITORING IN EARLY PREGNANCIES

Dharmaraj K¹, Nazir SF², Kennelly MM², O’Higgins AC²

¹UCD School of Medicine, University College Dublin, Ireland

²UCD Centre for Human Reproduction, The Coombe Hospital, Dublin, Ireland

Gestational diabetes mellitus (GDM) is hyperglycaemia that is recognized for the first time during pregnancy¹. There is no consensus as to what level of hyperglycaemia defines GDM and different diagnostic tests are used. Continuous glucose monitoring (CGM) is emerging as a novel way of assessing hyperglycaemia in pregnancy. The purpose of this project was to explore different approaches to the evaluation of hyperglycaemia with CGM in the first trimester of pregnancy.

CGM sensors (FreeStyle Libre, Abbott) were applied in the first trimester of pregnancy. A food diary was given for completion concurrent with sensor use. Sensors were returned after 14 days. Data was analysed in Excel (Microsoft, WA, USA). Individual data was examined using nine different ways of defining hyperglycaemia including, lowest and highest daily readings, pre-breakfast readings, difference in daily readings, mean difference in daily readings, glycaemic variability and time within range defined as between 3.6–7.8 mmol/L.²

Data from 38 sensors were included in the study. Of these 86.8% (33/38) had 14 days of identifiable lowest/highest daily glucose readings and 44.7% (17/38) had ≥ 13 days of identifiable pre-breakfast readings. Of the nine methods of defining hyperglycaemia all selected a different subset of patients as being ‘hyperglycaemic’.

This study shows that patterns of glycaemic variability differ between patients. There is unlikely to be a single best way to defining ‘hyperglycaemia’. Further studies correlating patterns of glycaemic variability with clinical outcomes are needed.

References:

• 1. Cullinan J, Gillespie P, Owens L, Dunne F. Accessibility and screening uptake rates for gestational diabetes mellitus in Ireland. Health & Place. 2012;18(2):339–48.

• 2. Fishel Bartal M, Ashby Cornthwaite JA, Ghafir D, Ward C, Ortiz G, Louis A, et al. Time in Range and Pregnancy Outcomes in People with Diabetes Using Continuous Glucose Monitoring. Am J Perinatol. 2023;40(5):461–6.

Presenting Author:Krithika Dharmaraj

Supervisor: Assoc Prof Amy O’Higgins

Co-Supervisor: Assoc Prof Mairead Kennelly

AWARENESS AND ATTITUDES ON NON-INVASIVE PRENATAL TESTING: A PATIENT SURVEY

Siu KYE¹, Nazir SF², O’Higgins AC²

¹UCD School of Medicine, University College Dublin, Ireland

²UCD Centre for Human Reproduction, The Coombe Hospital, Dublin, Ireland

Non-Invasive Prenatal Testing (NIPT) utilises cell-free fetal DNA to screen for aneuploidy from ten weeks gestation¹. Since its introduction, it has been widely adopted with varying implementation strategies worldwide². In Ireland, NIPT is currently not provided as part of routine antenatal care and is only available privately, costing around €400-€500. The aim of this study was to build on limited Irish data regarding information on NIPT.

This was a cross-sectional observational study conducted at The Coombe Hospital. Self-administered questionnaires were distributed to patients attending antenatal care and their partners. Results were recorded and analysed through Excel Spreadsheet, SPSS and NVivo. Descriptive statistics, chi-square test and qualitative analysis were performed.

A total of 321 of 325 surveys were analysed. Of them, 76% (244/321) had heard of NIPT, and 83.4% (266/321) had not availed of NIPT previously. Those aged over 30 were more likely to have heard of NIPT (181/224, p = .003) and have availed of NIPT (44/223, p < .001). Those who have lived in Ireland for less than 20 years were more likely to choose to have NIPT (59/96, p = .02).

Our results show that there are a significant proportion of people attending for antenatal care who are not aware of NIPT. There were differences in awareness of and attitudes towards NIPT among different population. Our findings highlight the need for standardisation of information provision with NIPT to ensure equitable and quality care.

Acknowledgement:

The authors would like to thank all patients who participated in the questionnaire. Special thanks to the UCD School of Medicine and The Coombe Hospital for their support in this project.

References:

• 1. Mackie FL, Allen S, Morris RK, Kilby MD. Cell-free fetal DNA-based noninvasive prenatal testing of aneuploidy. The Obstetrician & Gynaecologist. 2017;19(3):211–8.

• 2. Gadsbøll K, Petersen OB, Gatinois V, Strange H, Jacobsson B, Wapner R, et al. Current use of noninvasive prenatal testing in Europe, Australia and the USA: A graphical presentation. Acta obstetricia et gynecologica Scandinavica. 2020;99(6):722–30.

Presenting Author: Ka Yuet Emily Siu

Supervisor:Prof Amy O’Higgins

SOMATIC COPY NUMBER ALTERATIONS IN VITAMIN D AND KIDNEY CANCER PATHWAYS AND THEIR PROGNOSTIC POTENTIAL IN RENAL CLEAR CELL CARCINOMA

Gandhi A¹, Hasan A², Arora S²

¹UCD School of Medicine, University College Dublin, Ireland

²Department of Cancer Prevention and Control, Fox Chase Cancer Center, Philadelphia, PA, USA

Renal clear cell carcinoma (ccRCC) has the highest mortality rate among genitourinary cancers with incidence rising. Recent studies have shown clinical potential of somatic copy number alterations (SCNAs) in predicting tumor aggressiveness and clinicopathological findings in ccRCC.¹ Similar somatic alterations in novel vitamin D pathways associated with decreased serum concentration in RCC and RCC-specific genes known to cause RCC hereditary syndromes are observed in sporadic ccRCCs.² This study aims to identify SCNAs in these ccRCC pathways (Vitamin D & RCC-specific) as potential prognostic and predictive biomarkers.

TCGA PanCancer Atlas ccRCC datasets were examined using cBioportal. For each gene, survival and mRNA expression data were classified by SCNA subtypes (deep deletion, shallow deletion, diploid, gain, amplification). Using GraphPad Prism, Kaplan–Meier analysis was conducted to assess cancer outcomes by SCNA subtype in each gene, and mRNA expression was analyzed to examine changes in gene expression (confirmed with log-rank, one-way ANOVA, and Mann–Whitney tests (p < 0.05)).Among vitamin D genes, VDR gain, CYP27B1 gain, and CYP2R1 shallow deletion SCNA subtypes correlated with decreased overall survival (p = 0.03, p = 0.04, p = 0.007). Among RCC-specific genes, TSC1 and SDHD shallow deletion SCNAs correlated with decreased overall survival and disease-specific survival (p = 0.007, p < 0.0001, p = 0.0283, p = 0.0237). TSC1 shallow deletion and MET gain SCNAs correlated with decreased progression-free survival (p < 0.0001, p = 0.0165). Alterations in mRNA expression were also compared with related pathways to assess pathogenicity in ccRCC. These findings identified these SCNAs in vitamin D genes VDR, CYP27B1, & CYP2R1 and RCC-specific genes TSC1, SDHD & MET as potential prognostic and predictive biomarkers.

References:

• 1. Tsuyukubo T, Ishida K, Osakabe M, Shiomi E, Kato R, Takata R, et al. Comprehensive analysis of somatic copy number alterations in clear cell renal cell carcinoma. Molecular Carcinogenesis. 2020;59(4):412–24.

• 2. Jeon S-M, Shin E-A. Exploring vitamin D metabolism and function in cancer. Experimental & Molecular Medicine. 2018;50(4):1–14.

Presenting Author:Arjun Gandhi

Supervisor: Dr Sanjeevani Arora

A REVIEW OF PHARMACEUTICAL COMPANY GUIDANCE REGARDING ORAL OPIOID EQUIANALGESIC RATIOS

Mansour Y¹, Yong L¹, Taylor A², Davies A^1,2

¹UCD School of Medicine, University College Dublin, Ireland.=

²Academic Department of Palliative Medicine, Education & Research Centre, Our Lady’s Hospice, Harold’s Cross Road, Dublin, Ireland.=

Cancer patients can be switched from one opioid to another to improve analgesia and/or reduce adverse effects. The equianalgesic ratio (ER) is the ratio of the dose of two opioids required to produce the same analgesic effect ⁽¹⁾. Pharmaceutical companies produce a summary of product characteristics (SmPC) for drugs, which often include suggested ERs (for opioids). This project aims to identify ERs quoted in SmPCs for oral opioids, any differences between brands, and the evidence-base for the stated ERs.

165 SmPCs for different brands/formulations of oral morphine, oxycodone, hydromorphone, tramadol and tapentadol were reviewed, and 20 separate pharmaceutical companies were contacted about the evidence used to generate the stated ERs. All data was recorded on an Excel spreadsheet.

No data was available for tapentadol. The ERs for certain opioids varied between different brands (e.g. oxycodone, tramadol). The ER for oxycodone (versus oral morphine) varied from 1:2 to 1.3:2, whilst the ER for tramadol (versus oral morphine) varied from 6:1 to 10:1. None of the pharmaceutical companies were able to produce robust evidence to support the stated ERs as they responded with limited information, citing ineffectual data from trials or indeed directly referencing other SmPCs.

This project highlights the lack of evidence to support stated ERs, and a variation in stated ERs for some drugs. The latter reinforces the need for caution in using ERs in clinical practice, and the need to titrate the dose of the “new” opioid according to its effects (effectiveness, side effects).

Reference:

• 1. Natusch D. Equianalgesic doses of opioids – their use in clinical practice. British Journal of Pain. 2012 Feb;6(1):43–6.

Presenting Author: Yasmina Mansour

Supervisor: Prof Andrew Davies

Co-supervisor: Dr Amy Taylor

IMPACT OF TIME-RESTRICTED FEEDING ON CARDIOVASCULAR LESIONS IN EXPERIMENTAL METABOLIC SYNDROME IN MALE RATS

Alfurayj M¹, Rajendran H¹, Docherty N¹

¹UCD School of Medicine, Diabetes Complications Research Centre, Conway Institute, Dublin, Ireland

This study explores the potential effects of Time-Restricted Feeding (TRF) on cardiovascular health in male Spontaneously Hypertensive rats (SHR) exhibiting metabolic syndrome. The research investigates disturbances of circadian rhythm as potential contributors to the development of metabolic syndrome and subsequent cardiovascular damage [1].

The study employed a laboratory-based quantitative approach, focusing on three groups of rats: one with unrestricted access to a high-fat diet, one with access to the diet only during the dark phase, and another with two rations distributed during both light and dark phases. Histological analyses, involving tissue sectioning and staining, were conducted on heart ventricle and aorta samples. Quantification of cardiomyocyte cross-sectional area and aorta tunica intimal medial wall thickness was performed using specialized software.

Results revealed no significant differences in cardiomyocyte 2-D cross-sectional area and aorta tunica intimal medial wall thickness across the studied groups. Moreover, regression analysis did not uncover any significant associations between heart weight, blood pressure, and the mentioned cardiac indicators. The findings were in contrast with a study on intermittent fasting that demonstrated positive effects on heart ischemic injury and remodeling in rats [2].

However, the study acknowledges certain limitations. The relatively short duration of the study and the small sample size could have impacted the results. These findings underscore the need for more extensive and prolonged investigations with larger sample sizes to ascertain the true effects of TRF on cardiovascular health in the context of metabolic syndrome.

References:

• 1. National institute of general medical sciences [Internet]. National Institute of General Medical Sciences (NIGMS). [cited 2023 Aug 18]. Available from: https://nigms.nih.gov/education/fact-sheets/Pages/circadian-rhythms.aspx

• 2. Ahmet I, Wan R, Mattson MP, Lakatta EG, Talan M. Cardioprotection by Intermittent fasting in rats. Circulation [Internet]. 2005;112(20):3115–21. Available from: https://doi.org/10.1161/circulationaha.105.563817

Presenting Author: Marya Ayman A Alfurayj

Supervisor: Assoc Prof Neil Docherty

EVALUATING THE ROLE OF ASTROCYTES IN THE NEUROLOGICAL OUTCOMES ASSOCIATED WITH NEONATAL ASPHYXIA

Alfaris TM¹, Hjelseth S², Jimenez-Mateos EM², Caldwell M²

¹UCD School of Medicine, University College Dublin, Ireland

²Trinity Biomedical Sciences Institute, Trinity University College, School of Medicine, Dublin, Ireland

Neonatal asphyxia, leading to Hypoxic-Ischemic Encephalopathy (HIE), is significantly associated with infant mortality and poor neurological outcomes in surviving infants, such as cerebral palsy, epilepsy, intellectual disability and autism. New evidence has implicated neuroinflammation in neonatal brain damage following birth asphyxia and subsequent long-term neurological outcomes. While astrocytes are involved in mediating the neuroinflammatory response, their role in these outcomes is unknown. Using a mouse model, this project evaluated the acute response of astrocytes to neonatal hypoxia by assessing astrocyte populations in the hippocampus. This was done using immunohistochemistry for GFAP (glial fibrillary acidic protein), a widely used astrocyte marker. Images were counted and subjected to statistical analysis to quantify the involvement of astrocytes. Results showed overall astrocyte populations increased post-hypoxia relative to same age controls. Implications would include further research on neuroprotection in the management of HIE, as neuroinflammatory cells have proven to further the pathogenesis of HIE, astrocytes could be a therapeutic target. Future steps would involve morphometric analysis of astrocytes in the hippocampus through skeleton analysis.

Presenting Author: Taiba Alfaris

Supervisor: Dr Eva Jimenez-Mateos

OUTPATIENT KIDNEY RECOVERY FOLLOWING ACUTE KIDNEY INJURY REQUIRING DIALYSIS: A SYSTEMATIC REVIEW

Chen A¹, Paquette-Canalonga C², Sikora L⁴, Clark EG^2,3,5

¹UCD School of Medicine, University College Dublin, Ireland

²Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada

³Nephrology Department, The Ottawa Hospital, Ottawa, Ontario, Canada

⁴Health Sciences Library, University of Ottawa, Ottawa, Ontario, Canada

⁵Clinical Epidemiology, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada

Acute kidney injury (AKI) is a serious health concern which has only increased in prevalence over the past decade. AKI-D or acute kidney injury requiring dialysis affects approximately 1–2% of hospitalized patients and is especially problematic as it associated with increased risk of complications and mortality. Of those who survive, 10–30% of AKI-D patients will require outpatient dialysis at the time of discharge or will require dialysis at some point within a 3–5-year period.

Improved understanding of the determinants which predict kidney recovery, particularly in outpatients who continue to require dialysis after their hospital encounter with AKI-D, could lead to better outcomes and better resource management. Thus, we have written a systematic review based on our lab’s previous work by Wang et al. which aims to evaluate the association between both patient and treatment related factors as well as short and long-term outcomes in patients who remain dialysis dependent following hospitalization due to AKI-D (1).

A literary search in EMBASE, MEDLINE and PubMed was conducted based on pre-specified criteria and without any language or publication date restrictions. 3523 studies were identified and then screened at two levels in a systematic review software, Covidence and a PRISMA diagram was created. Data from the 23 eligible studies was then extracted and a quality assessment was also performed. The data obtained was then assessed qualitatively to determine the directions of associations and quantitatively to determine the strength of said associations.

Our findings will help develop evidence-based management and guide long-term treatment planning for AKI-D patients.

Reference:

• 1. Wang C, Hiremath S, Sikora L, Sood MM, Kong J, Clark E. Outpatient kidney recovery after acute kidney injury requiring dialysis: a systematic review protocol. Systematic Reviews. 2019 Aug 22;8(1):214.

Presenting Author: Aidan Chen

Supervisor: Assoc Prof Edward Clark

CORRELATION BETWEEN THE PRESENTATION OF POSTNATAL POSTTRAUMATIC STRESS SYMPTOMS ON THE PREFERENCE FOR ELECTIVE CAESAREAN SECTION: A SUBSECTION OF SYSTEMATIC REVIEW OF THE BIDIRECTIONAL ASSOCIATATION BETWEEN MENTAL ILLNESS AND CAESAREAN DELIVERY

Ariff Shafzan S¹, Doherty A^1,2, and Crudden G²

¹UCD School of Medicine, University College Dublin, Ireland

²Mater Misericordiae University Hospital, Dublin, Ireland

Over the past decade, obstetricians have begun offering elective caesarean sections (ECS) based on psychiatric reasons, including where postnatal posttraumatic stress disorder (PTSD) has developed from prior traumatic childbirth experiences. This can subsequently lead to the presentation of tokophobia, or fear of childbirth (FoC). Earlier studies have suggested an association between these conditions. This study aimed to define the association between postnatal PTSD and tokophobia, and any relationship with future birthing preferences such as ECS.

The research drew from three databases: Medline, EMBASE, and PsychInfo. Thirty-seven studies were screened based on inclusion criteria including maternal request for caesarean section and/or ECS, presentation of tokophobia, and presentation of postnatal PTSD. After a full-text screening of 15 articles, ten were chosen for inclusion.

Results indicated a positive relationship between postnatal PTSD and tokophobia, with tokophobia being a primary determinant for ECS. Four articles identified an association between FoC and birth-related PTSD, suggesting that the relationship may be bidirectional. However, exact percentages within this sample were not formally defined in contrast to the nulliparous population. Fear of childbirth also emerged as a primary risk factor for maternal request for ECS.

Substantial research gaps remain regarding the association between postnatal PTSD and tokophobia, particularly in the context of multiparous women. Further exploration of this area could enhance tailored intervention strategies within perinatal mental health services for individuals dealing with postnatal PTSD and tokophobia and influence future birthing plans for subsequent deliveries.

Presenting Author: Sarah Ariff Shafzan

Supervisor: Assoc Prof Anne Doherty

Co-Supervisor: Dr Genevieve Crudden

THE ROLE OF SUBSTANCE USE IN EMERGENCY DEPARTMENT ATTENDANCE WITH SELF-HARM

Alabdulrahman M¹, Tan DSY², Rohan F², Doherty AM^1,2

¹UCD School of Medicine, University College Dublin, Ireland

²Mater Misericordiae University Hospital, Dublin, Ireland

Substance abuse and self-harm are both established risk factors for suicide, representing a significant concern in healthcare [1]. The aim of this study is to evaluate the association between suicidal ideation and substance misuse in an older population presenting to an inner-city Emergency Department (ED), including those associated with high-lethality attempts.

Electronic Records from a 8.5-year cohort of patients aged 65 year and older presenting to the ED with mental health triage codes (mental illness; behavioural disturbance; overdose and poisoning; and self-harm) were investigated, to examine the characteristics of older people presenting with substance use (alcohol and drugs). The study obtained data on patient characteristics and self-harm and suicidal ideation in the context of substance abuse. Data were analysed using SPSS: statistical analyses were performed using chi-square tests and independent sample t-tests. Ethical approval was granted by the Institutional Review Board at the Mater Hospital.

Over the time-frame studied, 638 patients aged 65 and older presented to the ED with a mental health problem. Substance use was significantly associated with a triage code of mental illness rather than the others (p = 0.011), having presented with self-harm (p = 0.017) and this patient group were significantly more likely to receive a psychiatric review in the ED (p < 0.001), and to receive a diagnosis of a depressive illness (p < 0.001) but less likely to be admitted to hospital (p = 0.03).

Understanding the association between self-harm, suicidal ideation, and substance misuse in older individuals can help to the establishment of appropriate interventions and preventative measures in this population.

Reference:

• 1. Hawton K, Saunders KE, O'Connor RC. Self-harm and suicide in adolescents. The lancet. 2012 Jun 23;379(9834):2373-82.

Presenting Author: Meshari Alabdulrahman

Supervisor: Assoc Prof Anne Doherty

ASSESSING THE CO-VARIATES OF SUICIDAL IDEATION AND SELF-HARM IN AN OLDER ADULT POPULATION ATTENDING THE MATER EMERGENCY DEPARTMENT

Tan DSY¹, Alabdulrahman M¹, Rohan F¹ and Doherty AM^1,2

¹UCD School of Medicine, University College Dublin, Ireland

²Department of Adult Psychiatry, Mater Misericordiae University Hospital, Dublin, Ireland

Mental illness is common in approximately 15% of the adult population aged 60 and over [1]. This population is expected to increase from 629,800 in 2016 to ~1.6 million by 2051 and with it, the rate of mental illness. Mental illnesses are related to most suicidal attempts and suicides worldwide [2]. Therefore, we aimed to identify the characteristics of patients aged 65 and over presenting to the emergency department (ED) with suicidal ideation and/or self-harm.

A retrospective study was initiated following ethical approval granted by the Institutional Review Board at the Mater Hospital. We examined and extracted clinical data from electronic records, with mental health triage codes: self-harm; overdose and poisoning; mental illness; and behaving strangely, of patients aged 65 and over presenting to the ED from August 2014 to December 2022. The data were then analysed using SPSS.

This study found that 638 patients presented to the ED with mental health triage codes. Of these 638, 134 (21.5%) had presented with self-harm and 150 (24.1%) with suicidal ideation. Those presenting with self-harm were significantly more likely to have a history of previous self-harm (p < 0.001) and of previously diagnosed mental illness (p < 0.001). Furthermore, women were significantly more likely to present with self-harm (p < 0.001), and depressive illness was the diagnosis most commonly seen in the self-harm cohort (p < 0.001).

Given the association of self-harm with depressive illness in those aged 65 years and older, this highlights the importance of prompt diagnosis and treatment of depression, along with other mental illnesses.

References:

• 1. Finnerty S. Mental Health Services for Older People. 2020. Available from: https://www.mhcirl.ie/sites/default/files/2021-01/Mental-Health-Services-for-Older-People-Report-2020.pdf

• 2. Bachmann S. Epidemiology of Suicide and the Psychiatric Perspective. 2018. 15(7):1425.

Presenting Author:Darlene Shu-Yi Tan

Supervisor: Prof Anne Doherty

CHARACTERIZATION OF SERINE/THREONINE KINASE MRCKΑ FOR THE OPTIMIZATION OF MRCKΑ INHIBITORS

Kelly G¹, Olson M²

¹UCD School of Medicine, University College Dublin, Ireland

²Department of Chemistry and Biology, Toronto Metropolitan University, Toronto, Canada

Metastasis is responsible for 90% of cancer-related deaths yet remains a poorly understood process (1). Serine/threonine kinase MRCKα, which has been shown to increase cell motility, exhibits elevated expression in infiltrating glioblastoma (GBM) cells and high-grade serous ovarian cancer (HGSOC) cells (2). Characterization of MRCKα by identification of substrates and other binding partners offers insights into cancer metastasis and potential novel therapeutic strategies.

To identify MRCKα substrates, a whole-cell lysate kinase assay using the pan-kinase inhibitor 5’-4-fluorosulphonylbenzoyladenosine (FSBA) was performed. HEK293 cells underwent lysis and FSBA treatment (20 mM), followed by recombinant MRCKα and ATPγS addition, and finally kinase reaction. Western blots were performed to visualize thiophosphate-bound substrates. Evaluating the MRCKα-GEF-H1 interaction involved co-immunoprecipitation of the proteins, followed by a kinase assay using ATPγS and subsequent visualization by western blot.

Initial pilot tests with FSBA-treated HEK293 cell lysates showed promise, evidenced by significantly reduced total thiophosphorylation compared to controls in western blot analysis. Nevertheless, FSBA treatment induced nonspecific protein precipitation, complicating western blot analysis due to inconsistent loading controls. Exploring the MRCKα-GEF-H1 interaction via co-immunoprecipitation indicated that MRCKα does not phosphorylate GEF-H1. Western blot analysis displayed no disparity in GEF-H1 phosphorylation between ATPγS-treated samples and controls.

These findings suggest the potential feasibility of the FSBA-treated whole-cell lysate assay for MRCKα substrate identification. Additionally, our experiments indicate that GEF-H1 is not an MRCKα substrate.

References:

• 1. Gupta GP, Massagué J. Cancer metastasis: building a framework. Cell [Internet]. 2006 Nov 17 [cited 2023 Aug 21];127(4):679–95. Available from: https://pubmed.ncbi.nlm.nih.gov/17110329/

• 2. Unbekandt M, Belshaw S, Bower J, Clarke M, Cordes J, Crighton D, et al. Discovery of potent and selective MRCK inhibitors with therapeutic effect on skin cancer. Cancer Res. 2018;78(8):2096–114.

Presenting Author:Garrett Kelly

Supervisor: Prof Michael Olson

ACETABULAR AUGMENTS USED IN REVISION HIP ARTHROPLASTY: MINIMUM 10-YEAR FOLLOW-UP OF IMPLANT SURVIVORSHIP, FUNCTIONAL SCORES, AND RADIOGRAPHIC OUTCOMES

Braunstein D¹, Greenberg A², Safir O²

¹UCD School of Medicine, University College Dublin, Ireland

²Department of Orthopedic Surgery, Mount Sinai Hospital, Toronto, Ontario, Canada

Addressing acetabular bone loss in the context of hip revision surgeries constitutes a significant challenge in orthopedics. The use of Trabecular Metal (TM) augments emerges as a viable solution, yet there is a lack of comprehensive data detailing their long-term outcomes [1, 2]. The purpose of this study was to evaluate the long-term implant survival rates, functional outcomes, and radiographic findings associated with the use of TM augments in hip revision surgery.

We conducted a retrospective review of 80 patients who underwent hip revision with TM augments over a 13-year period. Kaplan–Meier analysis was carried out, with functional outcomes assessed using the Harris Hip Score (HHS) and Oxford Hip Score (OHS). Radiographic analysis was conducted to assess incidence of osteolysis.

Kaplan–Meier analysis demonstrated impressive survival rates of 96.8% augment survival at 5 years and 92.3% at 10 years. There was a marked improvement in the functional hip scores: mean HHS rose from a pre-operative 39.35, indicative of severe pain and major functional limitations, to a 10-year post-operative 75.75, suggesting milder pain and reduced limitations. Likewise, pre-operative OHS, averaging at 15.09 (severe arthritis), improved to 36.8 (mild arthritis) at 5 years post-operation. The incidence of osteolysis was found to be 33.75% at the final radiographic follow-up.

Our study validates the use of TM augments for acetabular bone loss in hip revisions. Regular patient monitoring for osteolysis and prevention of late augment failure is vital. By providing robust long-term data, this study enhances the existing body of literature, thus guiding future surgical decisions.

Acknowledgement:

This study received no external funding.

References:

• 1. Jenkins DR, Odland AN, Sierra RJ, Hanssen AD, Lewallen DG. Minimum five-year outcomes with porous tantalum acetabular cup and augment construct in complex revision total hip arthroplasty. J Bone Joint Surg Am. 2017; 99(10):e49.

• 2. Löchel J, Janz V, Hipfl C, Perka C, Wassilew GI. Reconstruction of acetabular defects with porous tantalum shells and augments in revision total hip arthroplasty at ten-year follow-up. Bone Jt J. 2019; 101-B(3):311–6.

Presenting Author: Doris Braunstein

Supervisor: Dr Oleg Safir

Co-supervisor: Dr Arieh Greenberg

DEVELOPMENT OF A HIGH-FIDELITY SKIN MODEL WITH TENSIONED LANGER’S LINES FOR SURGICAL TRAINING

Walsh T¹, Jones J¹, Myles C¹

¹UCD School of Medicine, University College Dublin, Ireland

Langer lines describe the orientation of forces that cause cutaneous tension, resulting in a circular puncture mark in in vivo human skin to distort into an elliptical shape. This inherent skin tension is used clinically to determine the appropriate orientation of incisions and excisions to improve wound healing outcomes and obscure the resulting scars (1). The distribution, anisotropic orientation, density, and interconnectivity of collagen fibres in the reticular dermal layer plays a fundamental role in the magnitude and direction of Langer lines.

In this work, stereolithography 3D-printing is used to produce different mesh variants for recapitulating the reticular dermis collagenous network. Additive manufacturing 3D printing platforms have the benefits of high pattern resolution and manufacturing scalability. Flexible, swellable, and elastic 3D-printing resins and bulk silicone materials are utilized and characterized.

The mechanical properties of mesh density, pattern, and lattice angle are studied to produce anisotropic elliptical stretch under bidirectional tension, like that of in vivo human skin (2). The material properties of five layered and woven mesh variants are studied. Post-3D print processing is performed to optimize the hydrophilic surface characteristics of the materials and allow for deposition of surface graphics.

The proposed novel skin model incorporates a collagen-replicating mesh embedded in a layered silicone dermis. With applied tension, the model was found to accurately replicate human skin during a common plastic surgery procedure. The proposed tensioned skin model may have an important role in familiarizing the trainee with identifying and using Langer lines to perform incisions and reconstructions (1).

Acknowledgment:

The authors confirm that this research received no specific grant from any funding agent.

References:

• 1. Bichakjian CK, Johnson TM. Chapter 1 - Anatomy of the skin. Baker SR, editor. Local Flaps in Facial Reconstruction (Second Edition). Amsterdam (Netherlands): Elsevier; 2007;3–13.

• 2. Deroy C, Destrade M, Mc Alinden A, Ní Annaidh A. Non-invasive evaluation of skin tension lines with elastic waves. Skin Research and Technology. 2017 Aug 1;23(3):326–35.

Presenting Author:Tavia Walsh

Supervisor: Prof James Jones

Co-Supervisor: Mr Christian Myles

GAIN-OF-FUNCTION IN THE T CELL TYROSINE KINASE ZAP70 MAY DRIVE AUTOIMMUNITY AND IBD

Mech, E¹,Warner N^2,3, Batura, V^2,6, Hawkins, RW^2,3, Natu A^2,3, Zhang S^2,3, Lam, L^2,3, Long K^2,6, Gaibee Z^3,4, Church P^3,4, Muise A^2,6

¹UCD School of Medicine, University College Dublin, Ireland

²Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada

³SickKids Inflammatory Bowel Disease Center, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada

⁴Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada

⁵Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada

⁶Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada

Inflammatory Bowel Disease (IBD) is a chronic multisystem disease that significantly impacts pediatric populations. Gain-of-function (GOF) mutation of ZAP70, a regulatory kinase of the T-cell receptor signaling cascade and known IBD gene, has been associated with autoimmunity and inflammatory colitis.(1) Here we describe a novel heterozygous missense ZAP70 mutation identified in a pediatric patient diagnosed with IBD and acute immune thrombocytopenia (ITP) and assess the variant’s impact on T-cell and immune signaling.

The heterozygous ZAP70 variant was identified by whole exome sequencing and validated by Sanger sequencing. Isolated patient T cells were purified from cryopreserved peripheral blood mononuclear cells by negative selection and the ratio of phospho-ZAP70 (Y319) to total ZAP70 was quantified via western blot. Bulk RNA was extracted from patient and healthy control whole blood and sequenced via next generation sequencing. Differential gene expression was assessed using DESeq2.(2).

Sanger sequencing confirmed a heterozygous C > G nucleotide substitution causing missense mutation within exon 9 of ZAP70 in the proband. The mutation mapped to the regulatory interdomain B region of ZAP70, responsible for autoinhibition of kinase activity and signaling. Consistent with loss of autoinhibitory function in interdomain B, unstimulated patient T cells showed increased phospho-ZAP70 compared to healthy controls (n = 3). RNAseq showed upregulation of genes involved in T-cell kinase cascades and JAK-STAT signaling indicative of dysregulated T cell activation compared to healthy controls.

This novel ZAP70 variant leads to gain-of-function in T cell signaling, providing an opportunity for personalized medicine by repurposing existing kinase inhibitors to dampen hyperactive ZAP70 kinase activity.

References:

• 1. Ashouri JF, Lo WL, Nguyen TTT, Shen L, Weiss A. ZAP70, too little, too much can lead to autoimmunity*. Immunol Rev. 2022;307(1):145–60.

• 2. Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15(12):1–21.

Presenting Author:Eugene Mech

Supervisor: Dr Aleixo Muise

A PILOT FEASIBILITY STUDY ON USE OF VIRTUAL REALITY IN PERSONS WITH MOTOR NEURON DISEASES

Barry R^{1, 2}, O’Connell C², McCullum S²

¹UCD School of Medicine, University College Dublin, Ireland

²Stan Cassidy Centre for Rehabilitation, Research Department, Fredericton, New Brunswick, Canada

Motor Neuron Diseases (MND) are progressive, degenerative, and debilitating. This cohort of diseases includes conditions such as Amyotrophic Lateral Sclerosis (ALS), spinal muscular atrophy (SMA) and progressive bulbar palsy. This research aimed to determine whether adding breathing-based virtual reality as a part of post-hospital care in patients would be both a, liked by the patient, and b, decrease overall anxiety.

The primary outcome was the overall likeability of using virtual reality (VR) in persons living with motor neurone disease as a qualitative measure, using a questionnaire including a rating of 0–10 on the patients' overall experience. Secondary outcomes included pre- and post-measures of anxiety, using the State-Trait Inventory for Cognitive and Somatic Anxiety questions 1–21 for state anxiety (STICSA), as well as pre-and post-measures of SpO2 and heart rate. A total of five participants were recruited. All patients reported a decrease in STICSA by an average of 5.2 points and an average overall experience of 8/10. Major factors that contributed to this likability include ease of software, reduced heart rate immediately post-session, and a suitable duration of the session. Participants must have been outpatients at the Stan Cassidy Centre for Rehabilitation in Fredericton, New Brunswick, Canada.

It can be implied that virtual reality can be a useful tool in anxiety management for patients with limited motor function.

Acknowledgement:

The author would like to acknowledge the Stan Cassidy Centre for Rehabilitation for the use of their facility and equipment, as well as patient recruitment.

Presenting Author:Regan Barry

Supervisor: Dr Colleen O’Connell

Co-Supervisor:Mr Shane McCullum

TOWARDS PERSONALISED MEDICINE IN GENERAL PRACTICE: A NARRATIVE REVIEW & MIXED-METHODS PILOT STUDY

En KL¹, Broughan J², Melin K³, McCombe G¹, Cullen W¹

¹UCD School of Medicine, University College Dublin, Ireland

²Clinical Research Centre, School of Medicine, University College Dublin, Ireland

³University of Puerto Rico, San Juan, Puerto Rico, USA

Personalised medicine (PM) is a data-driven approach that tailors medical decisions to patients' characteristics¹. However, little is known about its application in general practice². This project aimed to address this by conducting (1) a narrative review exploring literature on PM in general practice, and (2) a pilot mixed methods study investigating perceptions of PM, its benefits, and barriers, among GPs. A narrative review of the literature was conducted in May–July 2023. Online databases (e.g., PubMed, Google Scholar) were searched for articles featuring terms corresponding to ‘PM’, ‘general practice’, and ‘primary care’. An online survey informed by the narrative review’s findings was developed and piloted among randomly and purposefully sampled GPs in August 2023. Qualitative interviews with GPs investigating the topic are ongoing.The narrative review identified six barriers to PM adoption in general practice: data protection issues, limited clinical guidelines around applying PM in practice, inequitable patient access to PM, reduced future care access for patients based on PM results (e.g., health insurance coverage issues due to genetic profiling), and concerns regarding the validity of genomic and biomarker testing. Random sampling of 45 GPs yielded two survey responses (response rate = 4.4%). Seven purposefully selected GPs also completed the survey. The survey findings highlighted that GPs are positive about PM's potential for improving care but they require supports including guidelines, training, staffing, and access to tests or labs. Genetic testing supports aside, GPs feel that they can enhance PM by getting to know their patients and their personal/social contexts better.

Acknowledgement:

The author would like to thank the family of the late Dr Mary J Farrell for funding this project, the Ireland East Hospital Group, and the UCD School of Medicine / College of Health and Agricultural Sciences.

References:

• 1. Maier M. Personalized medicine—a tradition in general practice! European Journal of General Practice. 2019 Apr 3 [cited 2023 July 26];25(2):63–4. Available from: https://doi.org/10.1080/13814788.2019.1589806

• 2. Bartlett G, Rahimzadeh V, Longo C, Orlando L.A., Dawes M, Lachaine J, Bochud M, Paccaud F, Bergman H, Crimi L, Issa A.M. The future of genomic testing in primary care: the changing face of personalized medicine. 2014 Oct 7 [cited 2023 July 26]; 11(5): 477–486. Available from: https://www.futuremedicine.com/doi/10.2217/pme.14.36?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed.

Presenting Author: Kai En Lee

Supervisor: Prof Walter Cullen

Co-Supervisor: Mr John Broughan

GENERAL PRACTITIONER ACCESS TO DIAGNOSTIC IMAGING: A SCOPING REVIEW OF BARRIERS AND FACILITATORS

MacManus A¹, McCombe G¹, Broughan J¹, Cullen W¹

¹UCD School of Medicine, University College Dublin, Ireland

Appropriate and efficient referrals for diagnostic imaging in general practice can have a significant effect on patient outcome (1). Thus, efforts have been made in recent years to improve General Practitioner (GP) access to diagnostic imaging.

This scoping review aims to review the relevant literature to highlight the challenges faced by GPs following the introduction of enhanced diagnostic imaging referral pathways and how these challenges might be addressed.

The Arksey and O’Malley six-stage process was utilised (2), along with the PRISMA extension for Scoping Reviews (PRISMA-ScR) checklist. A comprehensive search was conducted of ‘PubMed’, ‘Cochrane Library’, and ‘Google Scholar’. A filter was applied for papers between 2013 and 2023. Thirty-two papers from a wide range of countries were included, (Netherlands, UK, Ireland, USA, Switzerland, Denmark, Japan, Poland, India, Hong Kong, Australia, Singapore, Germany).

Challenges reported included increased workload for GPs, the increase in anatomical knowledge that was required of primary care physicians, and the need for increased training amongst GPs. With increased patient numbers attending general practices for diagnostic imaging, follow-up appointments and further testing, vast numbers of general practitioners reported feeling overworked. The high costs associated with training GPs to use various diagnostic imaging modalities was also reported.

These scoping review findings indicate that whilst these new referral pathways are beneficial, improved staffing, funding, and training within primary care facilities are necessary in order to improve patient outcomes both in Ireland and internationally.

Acknowledgement:

This project was funded by an educational grant from Medisec Ireland.

References:

• 1. Berg HF VM, Algra PR, Boonman-de Winter LJ.. Direct access to magnetic resonance imaging improved orthopaedic knee referrals in the Netherlands. Fam Pract. 2016;33(5).

• 2. Arksey H, O'Malley L. Scoping Studies: Towards a Methodological Framework. International Journal of Social Research Methodology. 2005;8(1):19–32.

Presenting Author: Aisling MacManus

Supervisor: Dr Geoff McCombe

Co-Supervisor: Prof Walter Cullen

OPTIMIZING THE PROCESS OF OUTPATIENT INDUCTION OF LABOUR: A QUALITY IMPROVEMENT INITIATIVE

Johal A¹, Cipolla A², Leung M²

¹UCD School of Medicine, University College Dublin, Ireland

²Credit Valley Hospital, Trillium Health Partners, Mississauga, Canada

Induction of labour (IOL) is a common obstetrical intervention that starts the process of labour artificially. For outpatient induction of labour, the goal is to get the cervix to soften, thin, and open. Outpatient mechanical and pharmacological methods of induction include foley catheter and prostaglandins. In 2019, an Induction Unit was developed at the Credit Valley Hospital and resulted in reduced induction visit times and average number of visits during the whole process. Our aim is to understand the current state of the induction process at Credit Valley Hospital, with the aim to identify areas for improvement that will maximise the use of existing resources, increase efficiency and result in a better patient experience.

Data was collected retrospectively on patients that presented to the hospital for a scheduled induction of labour. The data was used to determine the mean, median, max and min of the number of visits for foley catheter and prostaglandins. It was also used to calculate total length of stay in hospital for induction of labour and total time spend in the birthing suites unit.

The time duration between the nurse to the clinician seeing the patient was determined to be the longest. Foley catheters were determined to result in fewer outpatient visits, shorter length of time during the induction period and shorter stays in the birthing suites unit when admitted for labour. The induction unit requires more resources to decrease the time patient must wait before being seen by the on-call obstetrician. This can include training nurses, midwives and nurse practitioners to perform vaginal exams and initiate the induction process.

Presenting Author: Amanpreet Johal

Supervisor: Dr Amanda Cipolla

IMPACT OF COVID-19 ON DIABETES CONTROL AND COMPLICATIONS

O’Doherty E¹, Adam A^2,3, Shah H^2,3, Yu M^2,3, Jangolla S², Middlebeek R², Mottalis A², Hall E², Slahor K², King G^2,3

¹UCD School of Medicine, University College Dublin, Ireland

²Research Division, Joslin Diabetes Centre, Boston, MA, USA

³Department of Medicine, Harvard Medical School, Boston, MA, USA

COVID-19 has impacted global health, diabetes stands out as a significant factor influencing outcomes in affected patients. ^{1 2} However research on COVID-19’s effect on type 1 diabetes (T1D) is scant. This study examined the impact of COVID-19 on people with T1D and type 2 diabetes (T2D).

At Joslin Diabetes Centre, 206 patients undertook COVID antibody assays and a survey detailing vaccination status, past infections, and outcomes. We analysed electronic health records from January-2017 to June-2023 using STATA and Microsoft Excel.

97% of participants were vaccinated against COVID-19, 87% received a booster. T1D individuals showed notable blood glucose changes post-vaccination and infection compared to T2D (p < 0.01). 61% reported past COVID-19 infections, and 69% tested positive for the SARS-CoV-2 antibody. HbA1c reduced consistently during the pandemic (p < 0.001). Both T2D groups (AB+ and AB-) exhibited a substantial reduction in BMI during the pandemic (p < 0.001). T2D reported 17% higher prolonged COVID symptoms (p < 0.01). Metformin led to a 23% decreased risk of severe outcomes in T2D (p < 0.05). While ACE/ARBs use showed a higher infection rate (p < 0.05), it didn’t correlate with disease severity (p = 0.13). Diabetic retinopathy diagnoses increased notably during the pandemic, especially in severe cases (p < 0.05).

These findings reiterate the profound, multidimensional impact of COVID-19 on diabetes-related complications, highlight the nuanced complexities within diabetic populations (T1D and T2D), and may pave the way for therapeutic advancements. This study emphasizes the need for tailored care approaches during health crises.

References:

• 1. Muniyappa R, Gubbi S. COVID-19 pandemic, coronaviruses, and diabetes mellitus. Am J Physiol Endocrinol Metab. 2020; 318(5): E736–E741

• 2. Onder G, Rezza G, Brusaferro S. Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy. JAMA. 2020; 323(18):1775–6.

Presenting Author: Emer O’Doherty

Supervisor: Dr George King

DEVELOPMENT OF A MACHINE LEARNING MODEL FOR ESTIMATING PHQ-9 SCORES FOR DEPRESSION USING CLINICAL NOTES FROM REAL-WORLD DATA SOURCES

Murray Whelan K^{1, 2}, Leavy M², Alves P², Gerber J², Boussios C², Marci C²

¹UCD School of Medicine, University College Dublin, Ireland

²OM1 Inc, Boston, MA, USA

The Patient Health Questionnaire-9 (PHQ-9) assesses depressive symptoms and is widely used in mental health and primary care settings¹. Consistent capture over time is important for monitoring changes in symptoms, understanding treatment response, and tracking outcomes². Yet, documentation is inconsistent in real-world data (RWD) sources. This effort applied machine learning methods to estimate PHQ-9 scores using routinely-recorded data from clinical notes.

A machine learning model was developed to generate estimated (ePHQ-9) scores using clinical notes from psychiatrists. Data were drawn from OM1 Major Depressive Disorder (MDD) Dataset, containing data on over 490,000 MDD patients across the U.S.. Patients with recorded PHQ-9 scores and clinical notes (32,802 patients contributing 96,891 encounters) were used. Notes were transformed via medical language processing, and results reviewed by a subject matter expert. To assess model performance, the area under the receiver-operating-characteristic curve (AUC) was calculated using a binarised version of the outcome, and continuous ePHQ-9 scores were evaluated using Spearman R and Pearson R values.

The model had an AUC of 0.81, Spearman R value of 0.62 and Pearson R value of 0.61 when evaluating performance. Application to larger MDD Dataset resulted in the generation of new ePHQ-9 scores for 2,215,662 encounters (2.7× enrichment from clinician-recorded PHQ-9 scores) for 208,692 distinct patients.

Results demonstrate that PHQ-9 scores can be estimated with very good performance using a machine learning model applied to clinical notes, thus providing a more complete view of symptom severity and treatment response, and increasing utility of RWD sources for depression research.

Acknowledgment:

The authors indicated are employees of OM1, which is involved in issues related to the topic of this research.

References:

• 1. Siu AL, USPSTF. Screening for Depression in Children and Adolescents: US Preventive Services Task Force Recommendation Statement. Pediatrics. 2016;137(3):e20154467

• 2. Gliklich RE, Leavy MB, Cosgrove L, et al. Harmonized Outcome Measures for Use in Depression Patient Registries and Clinical Practice. Ann Intern Med. 2020;172(12):803–809

Presenting Author: Katelynn Murray Whelan

Supervisor: Dr Carl Marci

INVESTIGATION OF HEPATITIS E VIRUS IN COMMERCIAL PORK PRODUCTS IN IRELAND

Anderson P¹, Haverty R¹, Fletcher NF^1,2

¹UCD School of Veterinary Medicine, University College Dublin, Ireland

²UCD Conway Institute of Biomedical and Biomolecular Research, University College Dublin, Ireland

Hepatitis E virus (HEV) is a major cause of viral hepatitis worldwide, and it is the only zoonotic hepatitis virus. HEV is known to infect a broad range of species and can be transmitted to humans through the consumption of infected meat products. The source of autochthonous Irish HEV infections has been suggested to be linked to contaminated pork products, and indeed HEV has been identified in commercial pork products at point of retail in studies in countries of the European Union. This study investigated the presence of HEV in pork products from Irish supermarkets. A total of 178 RNA samples were extracted from a variety of pork products from Irish food retailers. The samples were extracted using the Qiagen RNeasy® kit according to the manufacturer’s instructions. HEV copy number was quantified using a reverse transcriptase polymerase chain reaction (RT-qPCR) assay to identify the presence of HEV RNA. In total, 16 samples contained detectable HEV RNA, all of which were pork liver pâtés of non-Irish origin. This pilot study indicates the presence of HEV RNA within pork-based foodstuffs in Ireland, and future studies will determine the presence of infectious virus within these products. This study highlights the importance of further investigation to determine the major sources of Irish HEV infection.

Presenting Author: Peyton Anderson

Supervisor: Dr Nicola Fletcher

THE AD-LINKED TREM2 R47H MUTATION: BOTH A CURRENT REVIEW AND DEVELOPMENT OF A NOVEL ALLELE SPECIFIC PCR PRIMER FOR DETECTION IN A CLINICAL POPULATION

Haghighat Talab T¹, Bergeron R², Chudalayandi P²

¹UCD School of Medicine, University College Dublin, Ireland

²Ottawa Memory Clinic, Ontario, Canada

Genetic variant R47H in the microglial triggering receptor expressed on myeloid cells 2 (TREM2) has been linked to an increased risk of late onset Alzheimer’s Disease (AD) [1] This mutation has been associated with an accelerated disease progression, altered microglial morphology, and a greater severity of amyloid and tau pathology [1]. Previous mouse model studies have attempted to uncover the mechanisms in which the loss of TREM2 function exacerbates AD pathology, however, the results have been confounding.

Through analysis of previous mouse models, this research aims to better understand the influence of this mutation on AD pathology. Furthermore, we intend to develop a set of novel double-mismatch allele specific (DMAS) primers using PCR capable of effectively detecting the single nucleotide polymorphism (SNP) mutation. To design DMAS primers, two mismatches (3’ end of the reverse primer and at the 4th base from this 3’ end) will be introduced to the wild-type allele specific primer identified using NCBI’s Primer-BLAST software® [2].

From the analysis it can be observed that the R47H mutation influences AD pathology in an amyloid, tau, and time-dependent manner. It appears protective in early stages of amyloid pathology yet harmful at advanced disease stages. In contrast, the allelic variant seems to aggravate tau pathology early on, then ameliorate it in later stages.

This study therefore provides a succinct review of the R47H mutation as well as a novel allele specific primer that can be used in subsequent experimental, clinical, or therapeutic avenues of research.

Acknowledgment:

The author would like to acknowledge funding from the Ottawa Memory Clinic.

References:

• 1. Korvatska O, Kiianitsa K, Ratushny A, Matsushita M, Beeman N, Chien WM, et al. Triggering Receptor Expressed on Myeloid Cell 2 R47H Exacerbates Immune Response in Alzheimer’s Disease Brain. Frontiers in Immunology. 2020 Sep 25;11.

• 2. Ye J, Coulouris G, Zaretskaya I, Cutcutache I, Rozen S, Madden TL. Primer-BLAST: A tool to design target-specific primers for polymerase chain reaction. BMC Bioinformatics. 2012 Jun 18;13(1).

Presenting Author:Thom Haghighat Talab

Supervisor:Dr Prakash Chudalayandi

Co-Supervisor:Dr Richard Bergeron

UPDATE OF SPINAL INJURIES IN CANADIAN ICE HOCKEY: THE IMPACT OF PREVENTION AND EDUCATION EFFORTS

Paolino MA¹, Tator CH¹

¹UCD School of Medicine, University College Dublin, Ireland

Starting in the 1980s severe spinal injury in ice hockey increased in prevalence to a rate not previously seen prompting Hockey Canada to institute rules and prevention programs¹. Tator et al¹ saw a correlation with implementation of rule changes/prevention programs and reduced spinal injury in ice hockey through the period of 2001–2011. Despite this, severe injuries continue and the need for analysis of more recent prevention methods is needed. The aim of this research is to collect and analyze spinal injury data and speculate on potential impacts of prevention methods.

Data collected for analysis was gathered via grey literature search. The initial search database was “ProQuest Canadian Newsstream”, and articles were screened for severe spinal injuries that occurred in Canadian ice hockey. Minor injuries of the spine such as sprains or strains were excluded from the study. The data collected includes demographic, mechanism, and neurological deficit information of the cases.

The grey literature search found 33 cases of severe spinal injury in Canadian ice hockey between the years 2011 and 2022. Of these cases, 97% occurred in male hockey players and 63% of the cases were in the age range 16–20. Checking and checks from behind into the boards are the most common mechanisms of injury at 15/33 and 11/33 respectfully. One third of injuries resulted in neurological deficit.

Current data between 2011 and 2022 show that spinal injuries have dropped in frequency in Canada but continue to occur, implicating the need for continuation of prevention and education¹.

Acknowledgment:

The author would like to acknowledge funding from the University Health Network (Toronto Western Hospital).

References:

• 1. Tator CH, Provvidenza C, Cassidy JD. Update and overview of spinal injuries in Canadian Ice Hockey, 1943 to 2011. Clinical Journal of Sport Medicine. 2016;26:232–8.

• 2. Westhead R. New Study Recommends Youth Hockey Leagues Ban bodychecking until age 18. TSN. TSN; 2022. Available from: https://www.tsn.ca/talent/new-study-recommends-youth-hockey-leaguesban-bodychecking-until-age-18-1.1855136.

Presenting Author: Marco Paolino

Supervisor: Dr Charles Tator

LEARNING HEALTH SYSTEMS AND LEARNING ORGANISATIONS IN POST-ACUTE REHABILITATION CARE: A SCOPING REVIEW

Rafter T¹, Christophers L², Torok Z², Hudson C², Trayer A³, Carroll A¹

¹UCD School of Medicine, University College Dublin, Ireland

²National Rehabilitation Hospital, Dublin, Ireland

³UCD Library, University College Dublin, Dublin, Ireland

Current healthcare systems require significant restructuring to meet the needs of an increasing aging population and changing health needs. Implementation of “learning organisations” (LO) or “learning healthcare systems” (LHS) has been suggested as a solution to this growing problem. Systems that continuously generate and apply evidence, innovation, quality, and value to provide better care. This is of value to non-acute healthcare settings such as rehabilitation, which are complex, multi-dimensional and multi-disciplinary in nature [1].

This scoping review aimed to systematically map and summarise the literature conceptualising and operationalising LHS in rehabilitation settings. Studies were included which define a LO or LHS; or describe an operating LHS/LO; or include the translation of research evidence generated from LHS/LO data into healthcare improvement within a rehabilitation context. Study designs such as quantitative, qualitative, mixed method studies, and case studies were included.

The guidelines from the Joanna Briggs institute methodology for scoping reviews was used for this review. The literature search was performed using a three-step search strategy: an initial limited search of two databases to identify relevant key words and index terms. The developed search string was adapted and applied across the following databases: OVID MEDLINE, EMBASE, CINAHL Plus, APA PsycINFO and COCHRANE. Followed by data extraction from relevant texts [2].

Significant effects of LHS application were recorded including, reductions in the total amount of inpatients days, inpatient admissions, and engagements with the emergency department as well as reduced associated costs. Evidence depicts Learning healthcare systems are successful in informing research and policy questions.

References:

• 1. Carroll A: Integrated Care Through the Lens of a Complex Adaptive System. Handbook Integrated Care. Springer Cham. 2021; 595–609.

• 2. Arksey H, O'Malley L: Scoping studies: towards a methodological framework. Int J Soc Res Methodol. 2005; (8)1:19–32.

Presenting Author:Tom Rafter

Supervisor: Dr Lauren Christophers

A PRELIMINARY QUALITATIVE INVESTIGATION INTO THE IMPACT OF DIETARY INTAKE AND NUTRITIONAL STATUS IN CARE HOMES ON ORAL HEALTH

Bradley D¹, Sallam A², Harvey M², Bradwel S², McKenna G²

¹UCD School of Medicine, University College Dublin, Ireland

²Queen’s University Belfast, Centre for Public Health, Institute of Clinical Science, Royal Victoria Hospital, Belfast, Ireland

As a result of aging populations, increasing numbers of people are ending up in various types of residential care throughout the developed world. In these settings, it is well documented that the standard of oral health of residents is worse than that of their community-based peers (1). Investigating a gap in the literature, this qualitative study aims to take a preliminary look at the role diet and nutrition play in this phenomenon, as part of a larger study within the QUB Centre for Public Health.

The study involved the recruitment of interviewees and completion of semi-structured interviews with participants (n = 17) from the following groups: Care home staff (n = 3), Healthcare professionals with experience working in care homes (n = 10), and Researchers and policy makers (n = 4). The interviews were automatically transcribed, verified, and analysed thematically.

The result of this analysis identified common themes that play a role in this phenomenon in Northern Ireland: lack of adequate resources and planning within the health service; poor levels of education on the subject of oral health amongst staff in homes; conflict between guidelines provided by different disciplines, in particular dietitians and dental professionals; common high sugar diets designed to counteract weight loss; and concerns that enforcing reductions in dietary sugar may decrease resident comfort and reduce their autonomy.

Further investigations will subsequently be conducted as part of the ongoing study, and a multidisciplinary approach to diet and nutrition for care home residents should be considered with input from dental professionals included based on these findings.

Acknowledgment:

The author would like to acknowledge funding from the National Institute for Health and Care Research.

Reference:

• 1. AJ Karki NMMM. Oral health status of older people living in care homes in Wales. British Dental Journal. 2015; 219: 331-334.

Presenting Author:Daniel Bradley

Supervisor: Prof Gerry McKenna

OUR INVESTIGATIONS INTO THE SIGNIFICANCE OF GRADE IN PATIENT PROGNOSIS WITH TRIPLE NEGATIVE BREAST CANCER: EXPANDING TO INCLUDE LONDON REGION

Farooq H¹, Hamm C²

¹UCD School of Medicine, University College Dublin, Ireland

²Schulich School of Medicine, Western University, London, Ontario, Canada

Triple negative breast cancer (TNBC) is a heterogenous form of cancer that lacks receptor expression for oestrogen and progesterone and lacks overexpression of human epidermal growth factor receptor-2⁽¹⁾. An important aspect in defining the character of a tumour is histologic grade, the degree of differentiation from normal. Grade is an important prognostic factor, however information of its use in TNBC remains limited⁽²⁾.

In our initial review of 305 patients from Windsor Regional Hospital Cancer Centre from 2004–2017, we found Grade 2 patients forecasted significantly inferior progression free and overall survival, as compared to Grade 3 patients. Overall survival rates for Grades 1, 2 and 3 were 90.12%, 64.4% and 77.2% (p = 0.019) with relapse rates of 70%, 55.6% and 77.2% (p = 0.04) respectively.

To validate these results, the data set was to include a further 515 patients from London Health Sciences Centre. Of those 515 patients, 100 were selected for the purposes of this initial review.

A retrospective chart review was conducted on these patients, alongside a literature review on grade and TNBC. Grade 2 patients had significantly higher incidence of relapse as compared to Grade 3 patients. Relapse rates were 45.45% and 25.29% (p = 0.001) respectively. Grade 2 patients had higher mortality rates than Grade 3, however no significant difference was found, reflecting the small sample size. Mortality rates were 45.45% and 39.10% respectively (p = 0.48).

These findings demonstrate the positive predictive value of grade in TNBC, which has the potential to impact clinicians and patients and suggest further research on this topic.

References:

• 1. Li CH, Karantza V, Aktan G, Lala M. Current treatment landscape for patients with locally recurrent inoperable or metastatic triple-negative breast cancer: a systematic literature review. Breast Cancer Res. 2019;21(1):143.

• 2. Sotiriou C, Wirapati P, Loi S, Harris A, Fox S, Smeds J, et al. Gene Expression Profiling in Breast Cancer: Understanding the Molecular Basis of Histologic Grade To Improve Prognosis. JNCI: Journal of the National Cancer Institute. 2006;98(4):262–72.

Presenting Author:Haniya Farooq

Supervisor: Dr Caroline Hamm

EVALUATION OF PUTATIVE BIOMARKERS IN CANINE KERATOCONJUNCTIVITIS SICCA

Van Dexter A¹, Hogg B¹, Duggan G¹, Murtagh K¹, Grimes T¹, McKenna M¹, Reynolds A¹

¹School of Veterinary Medicine, University College Dublin, Ireland

Canine keratoconjunctivitis sicca (KCS, dry eye disease) results from a deficiency of the tear film leading to chronic ocular surface friction and inflammation. KCS can result from alacrimia, in a neurogenic, iatrogenic or immune-mediated manner or secondary to endocrine/metabolic disorders. In human KCS, diagnostic biomarkers have been identified and isolated from Schirmer’s filter paper strips used to record tear volume.

The purpose of this study was to identify potential biomarkers present in canine KCS and evaluate whether RNA could be isolated from Schirmer tear test strips.

To identify biomarkers for canine KCS a scoping review of the literature was performed using Pubmed and keywords “keratoconjunctivitis sicca” AND canine”. Covidence was used for title and abstract screening using defined exclusion criteria. Full text screening was performed to identify canine KCS biomarkers. A pilot study was performed to determine whether RNA could be collected from tear volume on tvhe Schirmer’s tear test strips (AREC-E-20-23).

260 references were obtained and narrowed to 19 papers for full text extraction. The following biomarkers were identified: MUC5AC, conjunctival epithelial cell and lymphocyte remodelling, polymorphonuclear and/or mononuclear conjunctival infiltration, goblet cell number, total sialic acids including 9-O-acetyl-N-acetylneuraminic acid, T antigen Galβ1-3GalNAc, corneal temperature, tear film quantity and osmolarity, mucus tear ferning, water channel protein AQP5, lysozyme C, heat shock protein Beta-1, protein S100-A12, keratin type II cytoskeletal protein 1 & 5, corneal sensation, CD4, IL-6, IL-1 and TNFα.

Primers targeting the canine gene were designed using Primer BLAST. Following method optimisation, RNA (14 ng/µl) was extracted from Schirmer’s tear strip.

Putative KCS biomarkers were identified, covering inflammation, oxidative stress and mucins. Low concentration RNA was extracted from Schirmer’s tear strips. The next steps are to evaluate gene expression in tear samples, to confirm the presence of putative biomarkers.

Presenting Author:Andrea Van Dexter

Supervisor: Dr Alison Reynolds

INVESTIGATING THE GENETIC LANDSCAPE OF PEDIATRIC PRIMARY SCLEROSING CHOLANGITIS-INFLAMMTORY BOWEL DISEASE USING WHOLE EXOME SEQUENCING

Broer E¹, Warner N², Griffiths AM³, Muise A³, Ricciuto A³

¹UCD School of Medicine, University College Dublin, Ireland

²SickKids Inflammatory Bowel Disease Centre and Cell Biology Program, Research Institute, The Hospital for Sick Children, Toronto, Canada

³Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Canada

Primary sclerosing cholangitis (PSC) is a chronic liver disease and 70% of patients have inflammatory bowel disease (IBD). Although PSC-IBD is considered a polygenic disease, we hypothesize that, in a subset of children with PSC-IBD, disease is driven by rare defects with large effect sizes. We further hypothesize that there is relatively little overlap in monogenic variants between paediatric PSC-IBD and non-PSC IBD.

All patients included in this study were diagnosed with PSC-IBD before the age of 18 years. Whole exome sequencing (WES) was conducted on consented patients and their parents (when available). Nonsynonymous variants with a Combined Annotation Dependent Deletion prediction score ≥ 20 were prioritized for further review using a manual filtering system. Clinical data pertaining to patient demographics and characteristics were extracted from the Canadian Children IBD Network database.

Twelve participants underwent WES analysis (8 PSC-IBD patients and 4 parents). 87.5% of patients were classified as large duct PSC and 62.5% had ulcerative colitis (UC). Thirteen predicted damaging variants in 12 genes were identified in 75% of patients, including variants in PIK3CD and SLC10A2. Two of the variants were in monogenic IBD genes (PIK3CD and DOCK8). Little genetic overlap was observed between the 13 variants identified and those from a previously reported cohort of 1005 pediatric-IBD patients.

This is the first explorative study of WES in pediatric patients with PSC-IBD, providing pivotal data to guide future studies. The identification of potentially pathogenic variants in PIK3CD and SLC10A2 may help to better understand disease pathogenesis and guide future therapies.

References:

• 1. Mertz A, Nguyen NA, Katsanos KH, Kwok RM. Primary sclerosing cholangitis and inflammatory bowel disease comborbidity: an update of the evidence. Ann Gastroenterol. 2019; 32(2):124–33.

• 2. Crowley E, Warner N, Pan J, Khalouei S, Elkadri A, Fiedler K, et al. Prevalence and Clinical Features of Inflammatory Bowel Diseases Associated with Monogenic Variants, Identified by Whole-exome Sequencing in 1000 Children at a Single Center. Gastroenterology. 2020; 158(8):2208–20

Presenting Author: Emma Broer

Supervisor: Dr Amanda Ricciuto

GENE THERAPY IMPROVES SPATIAL MEMORY AND ALTERS HIPPOCAMPAL PROTEOMIC SIGNATURES IN THE R6/1 MOUSE MODEL OF HUNTINGTON’S DISEASE

Cooke Allen A¹, Gavin C^1,2, Glennon J^1,2

¹UCD School of Medicine, University College Dublin, Ireland

²UCD Conway Institute of Biomedical and Biomolecular Research, University College Dublin, Ireland

Huntington’s disease (HD) is an inherited neurodegenerative disorder caused by a mutation in the huntingtin (HTT) gene¹. HD presents with a variety of symptoms including motor dysfunction, cognitive impairment and psychological disturbances². HD research is primarily focused on the most heavily affected brain region, the striatum. However, there is evidence suggesting that the hippocampus may be involved in disease pathogenesis, particularly in terms of cognition².

The aim of this study was to explore the effect of gene therapy on spatial memory in the R6/1 mouse model of HD and to test the effect of HTT-lowering on the downstream hippocampal proteome.

Mice were treated with antisense oligonucleotide (ASO) to lower mutant HTT levels. The HTT-lowering effect of ASO was confirmed using RT-qPCR. The y-maze (forced alternation) test was used to examine the impact of ASO on spatial memory. Protein isolated from hippocampal brain tissue was analysed by mass spectrometry and subsequent pathway enrichment analysis was performed.

ASO treatment resulted in a 65% reduction in mutant HTT expression. ASO-treated mice display a preference for the novel arm during the y-maze task, while the vehicle controls do not, showing improved spatial memory. Differential protein expression data suggests mitochondrial, cell survival and LTP-related proteins are responsible for observed cognitive improvement. Pathway enrichment analysis indicates that protein clearance and metabolic pathways play a key role in HD. These results show that ASO can be used to improve the cognitive phenotype in a mouse model of HD and highlight downstream proteomic changes responsible for disease pathogenesis.

References:

• 1. MacDonald ME, Ambrose CM, Duyao MP, Myers RH, Lin C, Srinidhi L, et al. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell. 1993;72(6):971–83.

• 2. Harris KL, Armstrong M, Swain R, Erzinclioglu S, Das T, Burgess N, et al. Huntington's disease patients display progressive deficits in hippocampal-dependent cognition during a task of spatial memory. Cortex. 2019;119:417–27.

Presenting Author: Amber Cooke Allen

Supervisor: Dr Jeffrey Glennon

Co-Supervisor: Mr Cian Gavin

THE EFFECT OF DIETARY FIBRE ON SPLEENIC LYMPHOCYTE PHENOTYPE

Kavanagh H¹, Brady T², Azeez A², Baugh J²

¹UCD School of Medicine, University College Dublin, Ireland

²UCD Conway Institute of Biomedical and Biomolecular Research, University College Dublin, Ireland

An extensive proportion of the world’s population consume a Western Diet daily. Comprehension of its effect is needed to realise its impacts on our health, especially on our immune system. The recommended amount of dietary fibre is 30 g a day, with most people on a Western Diet receiving less than half of their daily needed amount.

T cells are the primary component of our immune system. The spleen contains the most significant amount of lymphoid tissue in the body, so holds a high responsibility in the immune response (1). The quality of the immune response can be measured through the T reg cell versus Th 17 cell balance. It is expected to see more T reg cells in mice on high-fibre diet. This hypothesis is driven from current research of a decreased amount of Th17 cells in a mouse that was high-fibre fed with hypertension induced (2).

6 mice were fed a high-fibre diet and 6 mice were fed a low-fibre diet for 5 weeks prior to the isolation of their splenocytes. SOCS3 (Suppressor of cytokine signalling-3) and FOXP3 (Forkhead transcription factor-3) were measured using QPCR. No significant results were received due to high variation. To make any definitive conclusions from this work, SOCS3 expression in the high-fibre had a slight lower Delta Ct value, indicating more expression.

Further experimentation of T cell isolation is required to reduce the amount of variation seen and to give a meaningful insight as to how SOCS3 and FOXP3 expression change due to the fibre intake.

References:

• 1. Steiniger BS. Human spleen microanatomy: why mice do not suffice. Immunology. 2015 Jul;145(3):334-46. https://doi.org/10.1111/imm.12469. PMID: 25827019; PMCID: PMC4479533.

• 2. Evans CEL. Dietary fibre and cardiovascular health: a review of current evidence and policy. Proc Nutr Soc. 2020 Feb;79(1):61-67. https://doi.org/10.1017/S0029665119000673. Epub 2019 Jul 3. PMID: 31266545.

Presenting Author: Hollie Kavanagh

Supervisor: Assoc Prof John Baugh