Student Summer Research Awards - SSRAAbstracts of the SSRA September 2022 meeting, UCD School of Medicine.

POST MORTEM FINDINGS IN GREY SEALS ( HALICHOERUS GRYPUS ) AND HARBOUR SEALS ( PHOCA VITULINA ) STRANDED ON THE IRISH COAST

Zhang H. 1 , Saint-Marc A. 1 , Imlau M. 1 , Plamenova E. 2 , Jahns H 1

1 Pathobiology Section, School of Veterinary Medicine, University College Dublin, Belfield, Dublin

2 Institute of Animal Health and Food Safety, Faculty of Veterinary Medicine, University of Las Palmas de Gran Canaria, Spain

Establishing the cause of death of marine mammals such as stranded seals can provide valuable information on the wildlife population, changes of the coastal marine environment, and the presence of zoonoses including influenza and other infectious diseases of veterinary importance.

Post-mortem examinations were conducted on 53 grey seals and 13 harbour seals stranded between November 2019 and February 2022 along the Irish coast to determine the cause of death, monitor parasite burden and establish a comprehensive tissue bank for future research. Detailed history, signalment, clinical signs, and pathological changes found on necropsy were recorded. Parasites were identified morphologically under the microscope. A wide range of tissue samples was fixed in 10% formalin and frozen.

Stranded seals were mostly neonates/juveniles, with a majority of them found during their respective pupping season. The most common causes of death were septicaemia often secondary to conspecific trauma, followed by emaciation and parasitic bronchopneumonia. Less frequently identified causes included: other types of trauma, peritonitis, endoparasitism including heartworm, myositis, aspiration pneumonia, pyothorax, pneumothorax and haemoabdomen. Overall, the respiratory and alimentary tracts were the organ systems most affected. The main parasites found were nasal mites ( Halarachne halichoeri) in 43.9% of seals, Anisakis nematodes in the stomach in 25.8% and lungworm ( Otostrongylus circumlitus) in 22.7%.

The above findings are similar to those reported in seals in the North Sea and North Atlantic. The large numbers of conspecific trauma and marked parasite burden may suggest intra and inter species encounters generated/reinforced by population density and/or local geographic conditions.

Acknowledgement

The authors would like to thank Brian Cloak, Michael Dixon and Amanda Lawlor for their technical support. Thanks to Seal Rescue Ireland for providing the data and seals for this project.

Presenting Authors: Han Zhang, Audrey Saint-Marc

Supervisor: Dr Hanne Jahns

SERUM NETOSIS EXPRESSION AND RECURRENCE RISK AFTER REGIONAL OR VOLATILE ANAESTHESIA DURING BREAST CANCER SURGERY: A PILOT, PROSPECTIVE, RANDOMISED SINGLE-BLIND CLINICAL TRIAL

Aghamelu O 1 , Buggy P 2 , Smith G 3 , Inzitari R 3 , Wall T 4 , Buggy DJ 1, 3, 4, 5, 6

1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland

2 School of Medicine, University College Cork

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

4 Department of Anaesthesiology & Perioperative Medicine, Mater University Hospital, University College Dublin

5 Outcomes Research, Cleveland Clinic, OH, USA

6 EU COST Action 15204 Euro-Periscope

Some experimental and retrospective clinical studies signal an association between certain anaesthetic techniques and tumour metastasis following breast cancer surgery 1,2 . Neutrophil Extracellular Trapping (NETosis) is an immunological process whereby neutrophils engulf tumour antigen then degranulate, leaving serologic markers. NETosis expression among breast cancer patients is associated with an increased risk of metastasis. We investigated the effect of two distinct anaesthetic techniques on the expression of NETosis in women who underwent potentially curative breast cancer surgery.

In a large clinical trial, women undergoing breast cancer surgery were randomly assigned to receive volatile general anaesthesia (GA) or propofol combined with paravertebral regional anaesthesia (PPA) for their surgery. Serum was taken preoperatively and 24 hours postoperatively. A subset of women (n=40) from this larger clinical trial were randomly selected and their serum was examined for two particular NETosis biomarkers, Neutrophil Myeloperoxidase (MPO) and citrullinated histone H3 (CitH3). NETosis was measured by ELISA using MPO and CitH3 biomarkers, which were the co-primary end-points.

Patient and breast cancer characteristics did not differ significantly between groups. Recurrence occurred in 7.5% patients. There was no difference in postoperative MPO in GA vs PPA (10.5±6.6 vs 11.5±4.7 ng ml -1 , p=0.60). Regarding CitH3, there was no difference postoperatively in GA vs PPA (3.6±2.3 vs 4.0±5.9, p=0.80). NETosis expression did not differ before or after anaesthesia and surgery in either group.

Anaesthetic technique did not affect NETosis expression in breast cancer patients, indicating that it is not a viable marker of the effect of anaesthetic technique on breast cancer recurrence.

Acknowledgements

We would like to thank the patients who kindly participated in this study and Helen Keane, Clinical Research Nurse.

References

Jaura A, Flood G, Gallagher H, Buggy D. Differential effects of serum from patients administered distinct anaesthetic techniques on apoptosis in breast cancer cells in vitro: a pilot study. British Journal of Anaesthesia. 2014;113:i63-i67.

Buckley A, McQuaid S, Johnson P, Buggy D. Effect of anaesthetic technique on the natural killer cell anti-tumour activity of serum from women undergoing breast cancer surgery: a pilot study. British Journal of Anaesthesia. 2014;113:i56-i62.

Presenting Author: Onyinye Aghamelu

Supervisor: Prof Donal J Buggy

Co-Supervisors: Dr Rosanna Inzitari, Ms Genevieve Smith

PRIMARY CARE IN RIOBAMBA, ECUADOR: EXPERIENCES OF GENERAL PRACTITIONERS CARING FOR THE QUICHUA POPULATION OF CACHA

Scanlon M 1 , Martínez P 2

1 UCD School of Medicine, University College Dublin, Ireland

2 Cachamsi, Medical Spanish Program, Ecuador South America

Quichua are the indigenous people of Ecuador. Their population is predominantly located in Cacha, and is served by local clinics and community programmes led by general practitioners. The aim of this research was to examine primary care delivery in the community, identifying challenges faced when caring for a rural and impoverished population. This was assessed by observing general practitioners as they worked in the community, attending to patients in both clinical and home-care settings.

Malnutrition is the main etiology of disease in Cacha. Multivitamins are carried and dispensed – when available - by all doctors. Due to the distance from Riobamba’s hospital, pregnant women are closely monitored. If a pregnancy-related death occurs under a specific doctor’s supervision, they are fined and removed from practice. Due to the extreme altitude of Cacha the infectious diseases common in populations without access to running water tend to be infrequent. Finally, it was also impossible to ignore the context in 1 which this research took place. A principal challenge faced was vaccine hesitance. Many individuals believed the vaccine to be part of a government plan to exterminate indigenous elders. Furthermore, vaccine availability was observed to be sporadic, with doctors often being told only hours before planned vaccination events that no vaccine would be arriving.

The results of this study show that general practitioners serving the Quichua face broad challenges in caring for the population. These challenges are systemic; they are the sequelae of an interaction between many factors - economic, historic, geographic, racial, and governmental.

References

Global WASH Fast Facts [Internet]. Cdc.gov. 2021 [cited 2021 Aug 1]. Available from: https://www.cdc.gov/healthywater/global/wash_statistics.htmlruo

Presenting Author: Maris Scanlon

Supervisor: Dr Pablo Martinez

EFFECT OF TEMPERATURE ON CELLULAR HYPOXIA-INDUCIBLE FACTOR RESPONSE IN CACO-2 EPITHELIAL CELLS

Lee ES 1 , Taylor CT 2

1 UCD School of Medicine, University College Dublin, Ireland

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

The Hypoxia-Inducible Factor (HIF) pathway has been a subject of intensive study for its role in cell survival in hypoxic conditions. Inflammation, on the other hand, is a process that can activate under the stressful condition of ischemia. Calor, or heat, forms a part of the characteristic cellular inflammatory response. The currently expanding research paradigm on the action of capsaicin on cell membrane ion channels elucidate heat’s role as more than an environmental factor; it is also a potential cellular signal. Therefore, this project establishes a connection between heat and HIF activity in Caco-2 epithelial cell lines.

Cells were treated at 40 °C for 48 hours against a control of 37 °C incubation, and in the final 24 hours, the hypoxic condition was simulated by the application, to both groups of cells, of Prolyl Hydroxylase Inhibitor drug named DMOG on a time course (2h, 4h, 6h, 24h). The Western Blot procedure was then conducted to stain for levels of HIF-1α subunit, the component of HIF that is most importantly regulated by hypoxic responses.

Results show that at 40 °C, the expressed level of HIF-1α decreases, suggesting a down-regulation of the HIF pathway at the higher, inflammatory temperature. This points to a negative feedback mechanism between heat and ischemic recovery in the context of inflammation control.

Further research that extends the existing understanding of the inflammatory process and its associated factor is pertinent to the field of pathophysiology.

Presenting Author: (Eddie) Eun Sang Lee

Supervisor: Dr Cormac T. Taylor

ARE RESIDENTIAL CARE FACILITIES USING THE FREDA PRINCIPLES WHEN DEALING WITH ADVERSE EVENTS?

Dignam C 1,2 , McGrane N 2 , Keyes LM 2

1 UCD School of Medicine, University College Dublin, Ireland

2 Health Information and Quality Authority, Cork, Ireland

Effective management of residential care facilities (RCFs) includes their ability to manage adverse events while maintaining the human rights of the resident. The aim of this research was to identify evidence of human rights of residents being upheld or violated in RCFs in Ireland through analysis of notifications of allegations of abuse.

A sample of notifications of allegations of abuse, n=114, stratified by service-type, risk rating and year, was drawn from the Database of Statutory Notifications from Social Care in Ireland (2021), from notifications received in 2020 and 2021. Content analysis of the sample was conducted independently by two researchers to identify occasions where FREDA principles (fairness, respect, equality, dignity and autonomy) (Curtis & Exworthy, 2010) were being upheld or violated.

The majority of the codes identified in the sample were examples of violations of respect / dignity in the incident. The second most common was examples of the same being upheld in the management of an incident. Most of the violations were in the form of peer to peer interactions, and the majority of evidence of rights being upheld was in the form of staff comforting residents in the aftermath of the alleged incident.

In the context of allegations of abuses, there was evidence of residents’ rights being upheld by staff. There was also evidence of relatively minor violations, largely from peer to peer interactions. Monitoring for patterns of these interactions and taking preventative action would help ensure resident human rights are upheld in RCFs.

References

Curtice, M.J. and Exworthy, T., 2010. FREDA: a human rights-based approach to healthcare. The Psychiatrist, 34(4), pp.150-156.

Health Information and Quality Authority (2021). Database of Statutory Notifications from Social Care in Ireland (Open Access), https://www.hiqa.ie/sites/default/files/2021-02/Database-of-statutory-notifications-from-social-care-in-Ireland-2013-2020.csv

Presenting Author: Celine Dignam

Supervisor: Dr Niall McGrane

DEVELOPMENT OF A COLLAGEN-BASED HYDROGEL SYSTEM TO MODEL PANCREATIC DUCTAL ADENOCARCINOMA

Xavier S 1, 2 , Lu JYS 1,2 , Doyle, C 1,2 , Gars M 1,2, 3 , Thorpe SD 1,2

1 UCD School of Medicine, University College Dublin, Ireland

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

3 École des Bio-Industries, Cergy Cedex, France

The 5-year survival rate for pancreatic cancer is 8-11%, the lowest of any common cancer type, due to limited treatment options and late diagnosis. 1 Disease progression is mediated by dense collagenous stroma surrounding a neoplastic epithelium. 2 By acting as a barrier to drug delivery and immune cell access, the stromal extracellular matrix provides therapeutic resistance. 2 The collagenous stroma observed in PDAC is not well represented in current in vitro models. The aim of this project is to develop a fibrillar collagen-based hydrogel system to model the tumour microenvironment in pancreatic ductal adenocarcinoma.

Collagen hydrogels were created using bovine type I collagen (TeloCol®-10) with final collagen concentration of 1.0, 2.0 or 3.0 mg/mL. Metastatic pancreatic cancer cell line, SUIT2-007, and non-metastatic pancreatic cancer cell line, BxPC-3 were incorporated into gels at 1×10 6 cells/mL. Gels were cast in ibidi imaging slides for assessment of cell viability using calcein-AM and ethidium homodimer. Gel contraction with time was used to assess cell contractility, with gels placed in 48-well plates pre-treated with bovine serum albumin to prevent gel attachment. Cell contractility was quantified based on percent gel contraction relative to initial surface area. Cell proliferation was also determined using alamarBlue.

Both cell types were 100% viable in gel conditions investigated. Both cell types were successfully cultured in collagen gels, with soft gels facilitating cell-mediated contraction indicative of collagen remodelling.

This model system could be used to assess drug treatment modulation of cell contractility and matrix remodelling.

Acknowledgments

S Xavier received a Translational Research Summer Studentship from the Irish Cancer Society (TSS22XAV) to fund this project. The authors thank Anwesha Sarkar and the members of Dr Thorpe’s lab for technical assistance and project discussion.

References

Pancreatic cancer [Internet]. Irish Cancer Society. 2022 [cited 9 August 2022]. Available from: https://www.cancer.ie/cancer-information-and-support/cancer-types/pancreatic-cancer

Presenting Author: Shanu Xavier

Supervisor: Dr Stephen Thorpe

ASSESSMENT OF CELL-MEDIATED COLLAGEN REMODELING IN PANCREATIC CANCER USING LABEL-FREE IMAGING

Jarren LYS 1,2 , Xavier S 1,2 , Doyle C 1,2 , Thorpe SD 1,2

1 UCD School of Medicine, University College Dublin, Ireland

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

Collagen plays a significant role in the development of pancreatic cancer. More specifically, desmoplasia has been shown to both confer chemoresistance 1 and promote the progression of pancreatic ductal adenocarcinoma (PDAC) 2 . In vitro models like collagen hydrogels serve as a good platform in studying PDAC because processes such as desmoplasia can easily be observed. The objective of this study was to assess collagen remodelling in the vicinity of pancreatic cancer (SUIT-2) cells via label-free imaging.

Acellular collagen gels were made from type I bovine telocollagen at final concentrations of 1, 2, 3, and 5.56 mg/mL. Collagen gels were imaged with confocal reflectance microscopy and images analysed with CTFire using MATLAB to quantify fibril architecture. To characterise collagen gel mechanical properties, rheology was conducted with both strain and frequency sweep tests performed. Later, SUIT-2 cells were incorporated into hydrogels of different collagen concentrations and again imaged with confocal reflectance microscopy. The pixel intensity of collagen fibrils was analysed to assess collagen contraction around cells.

Collagen fibril length decreased with increasing collagen concentration, whilst no significant differences were found in fibril width. The storage modulus at 0.1 Hz was taken from all frequency sweep tests performed and was found to increase with collagen concentration ranging from 21.04±9.09 to 411.39±110.66 Pa for 1 and 5.56 mg/mL respectively. Elongated cancer cells were associated with condensation of collagen fibrils indicative of matrix remodelling.

This study suggests elongated cells resembling a mesenchymal morphology have a larger impact on their surroundings compared to those of epithelial morphology.

Acknowledgements

The authors acknowledge funding from the Anatomical Society via an Anatomical Society Undergraduate Summer Vacation Scholarship. We thank all members in Dr Stephen Thorpe’s lab, including Michelle Fox, Leah Fallon, Maëla Mars, and Anwesha Sarkar for help and useful discussions.

References

Wu P, Gao W, Su M, Nice EC, Zhang W, Lin J, et al. Adaptive Mechanisms of Tumor Therapy Resistance Driven by Tumor Microenvironment. Frontiers in Cell and Developmental Biology. 2021 Mar 1; 9.

Cannon A, Thompson C, Hall BR, Jain M, Kumar S, Batra SK. Desmoplasia in pancreatic ductal adenocarcinoma: insight into pathological function and therapeutic potential. Genes & Cancer. 2018 May 21; 9(3-4).

Presenting Author: Jarren Yi Sheng Lu

Supervisor: Dr Stephen Thorpe

DEVELOPING A FOOD DATABASE FOR APPLICATION TO PEPTIDOMIC ANALYSIS OF RESIDUAL FOODS IN STOOL SAMPLES

Gonzales Castillo JA 1 , Agoni C 2 , Shields D 2

1 UCD School of Medicine, University College Dublin, Ireland

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

Mass spectrometry has revolutionised the study of proteins, particularly in its application in the characterisation and quantification of proteins in many samples including those obtained from stool. Although stool samples have been extensively studied and are known to contain host proteins, proteins expressed by microbes and food proteins; not much attention has been paid to food proteins and peptides. This study aimed to develop a database of food proteins that are common in the western diet or that are contained in protein-rich foods.

In order to curate this database a review of the literature was done so as to identify the protein-rich foods that are eaten commonly as part of the western diet. Proteome maps were found in order to add proteins to the database. Protein homologs were used when no proteome map could be found. A set of criteria was used to select a sequence from a number of options on UniProt. UniProt was used to search for all the information that is presented in the database.

A total of 1362 proteins have been included in the database. These proteins are found in maize, quinoa, sorghum, potato, soybean, green pea, rice, duck, goat, pig, cow, chicken, cow milk and chicken eggs.

It is possible that the lack of understanding of how individual food proteins modulate health and disease, arises from the absence of a database like the one that is presented here. Hopefully this database can be updated and improved upon and contribute to the understanding of how food proteins interact with the body’s homeostasis.

Presenting Author: José Augusto Gonzales Castillo

Supervisor: Prof Denis Shields

EXPLORATION OF DUAL MIRNA/STATIN THERAPY TARGETING VASCULAR SMOOTH MUSCLE CELL DYSFUNCTION IN ATHEROSCLEROTIC CVD

Giardini E 4 , Vartak T 1 , Moran B 2 , Kennedy C 1 , Barry M 3 , Godson C 1 , Brennan E 1

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

2 Clinical Bioinformatician, Dept. of Pathology, St. Vincent's University Hospital, Dublin, Ireland

3 Department of Vascular Surgery, St. Vincent's University Hospital, Dublin, Ireland

4 UCD School of Medicine, University College Dublin, Ireland

Atherosclerotic cardiovascular disease (AsCVD) is an inflammatory condition involving a build-up of low-density lipoprotein cholesterol in arteries. Infiltration of immune cells and activation of endothelial and vascular smooth muscle cells (promoted by factors such as Klf4) can result in the development of fibromuscular plaques. Statins are used as a treatment, however, there is interest in exploring combination therapies for the significant proportion of patients intolerant to statins. Our group previously identified a role for the let-7 miRNA family, with let-7d levels reduced in AsCVD. We aimed to study the impact of a dual statin/let-7d miRNA combination therapy targeting human aortic smooth muscle cell (HaOSMC) activation and pro-inflammatory pathways in AsCVD.

Primary HAoSMCs (Lonza) were transfected with Let-7d mimic or negative control (20nmol/L;24h) and treated with pro-atherogenic/pro-inflammatory TNF-α (10ng/ml;24hr) and Atorvastatin/Lovastatin (1µM;24h). RNA-seq transcriptomics was performed to identify genes differentially expressed following cell treatments (N=3;FDR p<0.05). Western blot analysis was performed on HAoSMC lysates to investigate FN1, TAGLN, CNN1 protein expression (N=3).

RNA-seq analysis demonstrated that TNF-α activated inflammatory pathways while statins and/or let 7d-mimic reduced their activation. The greatest inhibition of inflammatory pathways was observed following let-7d mimic/statin dual therapy. We also observed that statins upregulated Klf4 expression, while let 7d-mimic reduced it, a finding confirmed by Western Blot analysis. miRNA-mRNA network enrichment analysis using MIRNET 2.0 identified key miRNA predicted to act as master regulators in HAoSMCs in response to treatments. Top-ranked networks identified included mir-155, let-7b, and mir-16.

In conclusion, dual statin/let-7 combination therapy can modulate HAoSMC activation and attenuate key inflammatory pathways.

Presenting Author: Elena Giardini

Supervisor: Dr Eoin Brennan

THE CLINICAL SIGNIFICANCE OF TICKBORNE FEVER ON IRISH SHEEP FARMS

Beirne K 1 , Gilmore J 2 , McGettrick S 3 , Froehlich R 3 , Flaherty AM 3 , Ó’Muireagáin C 3 , Harte C 3 , Fagan S 4 , Sheehan M 5 , O’Shaughnessy J 6 , Mee J 7 , Keady T 8 , Zintl A 1

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

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

3 Sligo Regional Veterinary Laboratory, Doonally, Co. Sligo, Ireland

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

5 Kilkenny Regional Veterinary Laboratory, Blanchfieldsland, Co. Kilkenny, Ireland

6 Central Veterinary Research Laboratory, Backweston, Celbridge, Co. Kildare, Ireland

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

8 Teagasc, Animal & Grassland Research and Innovation Centre, Mellows Campus, Athenry, Co. Galway, Ireland

Anaplasma phagocytophilum is a gram-negative bacterium that is transmitted by the tick Ixodes ricinus and causes tickborne fever in ruminants, characterised by fever, weakness and immunosuppression [1]. This immunosuppression increases susceptibility to other infectious diseases such as tick pyaemia, pasteurellosis and listeriosis. The aim of this study was to investigate (a) the geographical distribution of A. phagocytophilum infections, and (b) whether the most common causes of death recorded in lambs concurrently infected with A. phagocytophilum differed from those reported in A. phagocytophilum -uninfected lambs.

Lambs born in 2021 and 2022 and submitted to the Regional Veterinary Laboratories (RVLs) in Sligo, Athlone and Kilkenny between 1 January 2021 and 31 May 2022 were included. Aborted and stillborn lambs were excluded. Animals were assigned A. phagocytophilum -positive and -negative status based on spleen sample PCR analysis. Post-mortem findings were collated from LIMS (Laboratory Information Management System).

Analysis of 494 lamb carcasses demonstrated that 36 were A. phagocytophilum -positive and 458 were A. phagocytophilum -negative. 31/36 of A. phagocytophilum -positive cases were Sligo RVL submissions. Preliminary results indicate that overall, the most recorded primary causes of death were pneumonia (19%, 95% CI:7%-32%), enteritis (17%, 95% CI:4%-29%) and enterotoxaemia (17%, 95% CI:4%-29%) in A. phagocytophilum- positive lambs and bacteraemia/septicaemia/toxaemia (16%, 95% CI:13%-20%) and enteritis (11%, 95% CI:8%-14% ) in A. phagocytophilum -negative lambs.

The results demonstrate the distinct geographical distribution of A. phagocytophilum infections on Irish sheep farms, reflecting the known tick vector distribution [2]. The primary cause of mortality in newborn lambs was infectious, regardless of their A. phagocytophilum infection status.

Acknowledgements

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

References

Stuen S. Anaplasma phagocytophilum-the most widespread tick-borne infection in animals in Europe. Vet Res Commun. 2007; 31:79–84.

Zintl A, Zaid T, McKiernan F, Naranjo-Lucena A, Gray J, Brosnan S, et al. Update on the presence of Ixodes ricinus at the western limit of its range and the prevalence of Borrelia burgdorferi sensu lato. Ticks Tick-borne Dis. 2020; 1:11.

Presenting Author: Kieran Beirne

Supervisor: Assoc Prof Annetta Zintl

Co-supervisor: Dr Shane McGettrick & Dr John Gilmore

COMPARISON OF YIELD AND COMPLICATIONS BETWEEN DIFFERENT TYPES OF PEDIATRIC RENAL BIOPSY DEVICES: A RETROSPECTIVE REVIEW

Youssef S 1 , Donnellan J 2

1 UCD School of Medicine, University College Dublin, Ireland

2 Department of Interventional Radiology, McMaster Children’s Hospital, Hamilton, Ontario, Canada

Increasing numbers of biopsies are frequently performed in children to diagnose and assess renal pathologies, and many methods and devices are employed with minimal comparisons of their relative strengths and weaknesses. The purpose of this study was to perform a retrospective review comparing the yield and complications between the Bard Magnum and Merit Corvocet Automatic Biopsy Devices and investigate our hypothesis that the latter device would demonstrate greater yield and complications owing to its mechanism.

112 pediatric kidney biopsies for 99 patients were performed by interventional radiologists with real-time ultrasound guidance between 2017 and 2021. 68 and 44 biopsies were completed using the Bard and Corvocet devices, respectively, with 2 biopsies completed using both devices. The mean age, weight, and body mass index were 138.13 months, 46.09kg, and 21.58kg/m 2 , respectively. 57 biopsies corresponded to females.

Patient demographics, blood count, yield, and complications were extracted and compared using t -tests and chi-square tests.

The most common complication was a hemoglobin drop (67.86%). The incidence of hematuria and hemoglobin drop >15g/dL were higher in the Corvocet group, X 2 (1, N =112) =5.72, p =.0168, and X 2 (1, N =112) =4.61, p =.0318, respectively. The overall mean number of cores and the mean amount and percentage of hemoglobin drop in transplant kidney biopsies were higher in the Bard group, t(109 )=2.1643, p= .0326, t(8 )=2.4884, p= .0376, and t(8 )=2.5743, p= .0329 respectively.

This is the first study to compare these biopsy devices and report on the performance of the Corvocet device. These findings should be considered when evaluating renal biopsy device choice.

Presenting Author:Salma Youssef

Supervisor: Dr John Donnellan

THE PATIENT PERSPECTIVE IN GENETIC TESTING FOR OBESITY SERVICES

Ko L 1 , Le Roux C 1

1 UCD School of Medicine, University College Dublin, Ireland

St. Vincents University Hospital, Clinical Research Centre is the first centre in Ireland to offer genetic testing for obesity services. Genetics explains approximately 70% of a persons bodyweight 1 , but until recently there has been no specific treatment which could be matched to specific obesity related genes. With the emergence of setmelanotide as an effective treatment for obesity which only works in a specific subset of obesity related gene mutations, there is a strong potential in the utility of genetic testing in obesity intervention 2 . This participatory action inquiry study aims to develop an evidence-based understanding of patient perspectives on genetic testing in obesity treatment including their hopes, motivations, fears and concerns using thematic narrative analysis. 14 adult patients with BMI>50 kg/m2, with hyperphagia from childhood and early onset obesity were interviewed and transcripts coded using nVivo software. Patients expressed key benefits of genetic testing were acquisition of knowledge, decrease in weight stigma, reaffirming beliefs about the physiological component of obesity, contribution to science, increased motivation to seek medical treatment for obesity, increased receptiveness to engage with medical staff, increased motivation to seek lifestyle changes, to have medical records of diagnosis for future treatments and more realistic weightloss expectations. Key motivations were to seek information and treatment, and vast majority of patients stated no concerns or fears with obtaining testing, but were perturbed by the implications for their children. It is recommended that genetic testing be offered to more patients sooner for earlier intervention and more informed obesity treatment.

References

Lamiquiz-Moneo, I. et al. (2019) Genetic predictors of weight loss in overweight and obese subjects. Scientific Reports , 9(1).

Ryan, D. (2021) Next Generation Antiobesity Medications: Setmelanotide, Semaglutide, Tirzepatide and Bimagrumab: What do They Mean for Clinical Practice? Journal of Obesity & Metabolic Syndrome , 30(3), pp.196-208.

Presenting Author: Louise Tak Ying Ko

Supervisor: Prof Carel Le Roux

EFFECTS OF EXTENDED CANNABIS ABSTINENCE ON ANHEDONIC SYMPTOMS IN PATIENTS WITH CO-MORBID MAJOR DEPRESSIVE AND CANNABIS USE DISORDERS

Garson E 1,2 , George TP 2,3,4,5 , Sorkhou M 2,3,4

1 UCD School of Medicine, University College Dublin, Ireland

2 Centre for Complex Interventions and Addictions Division, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada

3 Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

4 Institute of Medical Sciences (IMS), Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

5 Addictions Divisions, Centre for Complex Interventions, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada

Anhedonia involves a loss of interest or pleasure and is a primary unit of analysis in the diagnosis and treatment of depression. 1 The aim of this research was to assess A) if contingent reinforcement (CR) results in increased cannabis abstinence, B) if participants with comorbid major depressive and cannabis use disorders experience diminished anhedonic symptoms after 28 days of cannabis abstinence, and C) if CR is associated with improvements in anhedonia.

Participants were between the ages of 18 and 55 and met the DSM-5 diagnostic criteria for cannabis use disorder and major depressive disorder. Participants were randomly assigned to either a CR group (in which they received an extra $300 bonus given successful abstinence for 28 days) and a non-contingent reinforcement (NCR) group (in which they did not receive an extra monetary bonus). Urinary tetrahydrocannabinol carboxylic acid (THC-COOH) levels from day 28 were evaluated using the extended version of NarcoCheckTMTHC PreDosage test and compared between the cohorts with a two-sample T-test. Anhedonia was evaluated using the Snaith-Hamilton Pleasure Scale (SHAPS). Repeated measures ANOVA and mixed ANOVA tests with Bonferroni post hoc testing were performed to assess changes in anhedonic symptoms.

The results demonstrate that cannabis abstinence did not significantly differ between the CR and NCR groups (t(3)=0.335, p=0.759). Anhedonic symptoms significantly decreased during the first two weeks of the study (F(4,16)=4.778, P=0.010, n p 2 =0.544) and were not significantly affected by contingent reinforcement (F(1,3)=0.475, p=0.540, n p 2 =0.137).

These preliminary findings suggest an association between cannabis abstinence and improvements in anhedonia.

Reference

De Fruyt J, Sabbe B, Demyttenaere K. Anhedonia in depressive disorder: A narrative review. Psychopathology. 2020;53(5-6):274–81.

Presenting Author: Emily Garson

Supervisor:Dr Tony George

SERIOUS INJURIES SUSTAINED BY RESIDENTIAL CARE FACILITY RESIDENTS IN IRELAND: A CONTENT ANALYSIS OF STATUTORY NOTIFICATIONS

Kee-Woon Yin T 1 , Dunbar P 2 , Behan L 2 , Keyes LM 2

1 UCD School of Medicine, University College Dublin, Ireland

2 Regulation Directorate, Health Information and Quality Authority (HIQA), Cork, Republic of Ireland

Serious injury (SI) to a resident is a notifiable event in social care services in Ireland but is not clearly defined. This can lead to confusion on what constitutes SI for reporting purposes. Therefore, the aim of this study was to identify the primary causes of injury, as well as the injury type and location reported by social care services in order to improve regulatory data collection and inform the development of a definition for serious injury.

All SI notifications received in 2021 by residential care facilities for older persons and people with disability were extracted from the Database of Statutory Notifications from Social Care (n=3,693). 1 Thematic analysis was used to create codes for the injury type(s), location(s), and proximate and secondary causes, then grouped into themes. Analysis was conducted independently by two researchers, until saturation of themes was reached.

Nineteen types of injury were coded, with the most common being fractures and lacerations. There were 75 injury locations coded and sorted into themes based on their anatomical locations, with the hip and forehead being the most commonly reported sites. 26 codes were created for the causes of injury, of which falls were the most commonly recorded. There was a difference in the type of SI reported between the centres for older persons and people with disability.

The findings of this study will contribute to the development of a definition for SI which will apply for regulatory reporting purposes.

Reference

O’Regan S, McGrane N, Dunbar P, Dunnion M, Leistikow I, O’Connor LM. Public Reporting of Adverse Events from Long-Term Care Facilities for Older Persons and People with Disability in Ireland 2013-2019: Development of an Openly Accessible Database and Descriptive Analyses. Journal of the American Medical Directors Association. 2022 Aug;23(8):1328-1334.e2.

Presenting Author: Tashley Kee-Woon Yin

Supervisor: Dr Laura O’Connor

TRANSITION TO CLINICAL PRACTICE: EXPERIENCES OF GRADUATE MEDICAL STUDENTS COMPARED TO UNDERGRADUATE

Alkanderi AAHA 1 , Farren M 1 , and Higgins M 1

1 UCD School of Medicine, University College Dublin, Ireland

The purpose of this study was to explore if there are differences in the transition to clinical training between Graduate Entry Medicine students (GEMs) and Undergraduate Entry Medical students (UEMs).

This was a scoping review, following the steps described by Arskey and O’Malley. Three databases were searched (PubMed, Embase, and Scopus).

Twenty studies were identified that reviewed medical students transition to clinical training. No study directly compared UEMs to GEMs. Studies comparing outcomes between UEMs and GEMs focused on early and later stages of medical school training. Studies were focused on differences between preclinical education and academic knowledge. It was noted that in the earlier clinical assessments, GEMs performed better than UEMs due to their previous knowledge and experience. This slight advantage diminished towards the late stages of the clinical assessment.

Although inconclusive, a hypothesis can be formulated that GEMs have an easier transition than UEMs to clinical training due to previous knowledge and experience. This hypothesis was extrapolated from early experiences in medical school. This is an area for future research.

References

Dodds A., Reid K., Conn J., Elliott S., and McColl G. Comparing the academic performance of graduate and undergraduate entry medical students. Medical Education [Internet]. 2010 [cited 2022 June 28]; 44: 197-204. Available from: https://pubmed.ncbi.nlm.nih.gov/20059678/

Byrne A., Arnett R., Farrell T., Sreenan S. Comparison of performance in a four year graduate entry medical programme and a traditional five/six year programme. BMC Medical Education [Internet]. 2014 [cited 2022 June 28]; 14(28): 1-8. Available from: https://bmcmededuc.biomedcentral.com/articles/10.1186/s12909-014-0248-3

Presenting Author: Abdullah Alkanderi

Supervisor: Dr Mary Higgins

ANALYSIS OF SIGNALLING PATHWAY ACTIVITY IN HIGH-RISK CHILDHOOD BLOOD CANCERS

Bielazik A 1 , Jones L 2,3 , Bond J 1,2,3,4

1 UCD School of Medicine, University College Dublin, Ireland

2 Systems Biology Ireland, School of Medicine, University College Dublin, Dublin, Ireland

3 National Children's Research Centre, Dublin, Ireland

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

Acute myeloid leukaemia (AML) is the leading cause of blood cancer-related deaths in childhood. Mutations in paediatric AML commonly directly or indirectly target epigenetic modifiers. 1 Alterations affecting Polycomb Repressive Complex 2 (PRC2), a histone methyltransferase are linked to poor outcome and increased relapse risk in childhood AML. Moreover, alterations in PRC2 have been shown to aberrantly regulate cell signalling pathways in leukaemias, affecting survival, proliferation, and self-renewal capacity. 2 The study aimed to a) quantify alterations in signalling pathways following loss of the enzymatic component of PRC2 (EZH2) in AML and b) test kinase inhibitors that target altered pathways as potential novel treatment avenues.

To investigate the effect of EZH2 loss in AML we used three isogenic cell line models of EZH2 depletion; OCI-AML2, HL-60 and THP-1. Effects on signalling were investigated using mass spectrometry, immunoblotting and RNA-sequencing.

Proteomics, phospho-proteomics and transcriptomics showed increased expression and activity of components involved in the RAS/RAF/MEK/ERK signalling pathway. This was supported by immunoblotting which showed increased phosphorylation of MEK and ERK in KO cells compared to WT. As increased MEK/ERK activity may present a therapeutic vulnerability, we treated these cells using MEK inhibitors Trametinib and Cobimetinib. Unexpectedly, the KO cells were more resistant to MEK inhibition compared to WT.

These results show that loss of EZH2/PRC2 function leads to aberrant cell signalling in AML. While the use of MEK inhibitors as single agents was not effective against EZH2 KO cells, the use of MEK inhibitors in combination with other chemotherapy agents may prove fruitful.

References

Jones L, McCarthy P, Bond J. Epigenetics of paediatric acute myeloid leukaemia. British Journal of Haematology. 2019 Dec 5;188(1):63–76.

Presenting Author: Antoni Bielazik

Supervisor: Prof Jonathan Bond

FACTORS ENABLING OUTPATIENT TOTAL KNEE REPLACEMENTS IN A SMALL HOSPITAL

Fox ES 1 , Song J 2

1 UCD School of Medicine, University College Dublin, Ireland

2 School of Medicine, Department of Surgery, Faculty of Clinical Sciences, Hamilton, Ontario, Canada

Outpatient Total Knee Arthroplasty (TKA) is an elective procedure with increasing popularity, yet few small hospitals in Canada offer this service. The purpose of this study is to report on the short-term results of patients who have undergone an outpatient TKA in a small Canadian hospital and to discuss some of the challenges encountered when implementing such a program in a small hospital setting.

This retrospective cohort study included 83 TKAs that were performed by a single surgeon at the Welland Hospital in Welland, Canada between April 2021 and June 2022. Patients were divided into 3 groups: (1) intended outpatient, discharged outpatient; (2) intended outpatient, discharged inpatient; (3) intended inpatient, discharged inpatient. Primary outcomes were postoperative complications. Pearson chi-squared tests were used for analysis. Quality improvement points arising from a multi-disciplinary outpatient TKA task force were also examined and summarized.

Eighty-three patients (mean age = 69.9 ± 8.03 years, 56.6% female) underwent TKA. There were no patients in Group 2. There was no difference in complication rates between the groups (p = 0.776). Age (67.2 years vs. 70.9 years) was the only variable that had different means between the groups. The major challenges we encountered to implement and deliver the outpatient program were adjustment of physiotherapist shift times, resistance to anesthetic protocol change, and post-discharge physiotherapy location coordination.

Outpatient TKA is safe and feasible in a small hospital setting. Unique challenges to implementing such a program exist for small hospitals but can be overcome with sufficient planning and communication.

Presenting Author: Edward Spencer Fox

Supervisor:Dr John Song

UNDERSTANDING THE ROLE OF NON-HLA ANTIBODIES IN RENAL TRANSPLANT

REJECTION: A RETROSPECTIVE CASE-CONTROL COHORT STUDY

Jameel IK 1 , de Chickera SN 2 , Sidahmed A 2

1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland

2 University Hospital – London Health Science Centre, London, Ontario, Canada

The cause of antibody-mediated rejection (AMR) in kidney transplant patients has long been attributed to donor-specific antibodies (DSAs) targeting human leukocyte antigens (HLAs) and is well established in the literature. However, there are patients who experience graft rejection without DSAs. The strongest evidence of this comes from reports showing AMR in recipients of renal transplants from HLA-identical siblings [1]. This has suggested a role for non-HLA antibodies in AMR. HLAs are typically expressed on the cell surface of allograft endothelium whereas non-HLA antigens are usually cryptic and exposed after tissue injury. The aim of the study is to (i) determine whether there is an association between increased non-HLA antibodies post-transplantation and biopsy-proven rejection and (ii) identify the antibodies contributing to rejection.

Serum samples from 8 patients with biopsy-proven rejection and 5 control patients with delayed graft function or no known rejection on file prior to and post-transplant will be used in this retrospective case- control cohort study. Samples will be measured on a Luminex 200 flow analyzer, readout is given as median fluorescence intensity with a cut-off of 95% being used to determine positivity for the antibody. 39 antibodies will be investigated. Comparison between groups will be through independent t-tests. All patients with biopsy-proven rejection experienced increases in antibody levels, increases in 7 non- HLA antibodies post-transplantation were recognized as significant and thus associated with graft rejection.

References

Grafft CA, Cornell LD, Gloor JM, Cosio FG, Gandhi MJ, Dean PG, et al. Antibody-mediated rejection following transplantation from an HLA-identical sibling. Nephrology Dialysis Trans [Internet]. 2009 Oct 20;25(1):307–10. Available from: https://academic.oup.com/ndt/article/25/1/307/1912995?login=false

Presenting Author: Ibraheem Khaleel Jameel

Supervisor: Dr Abubaker Sidahmed

BEYOND BURNOUT: MEASURES OF MEANING AND COMMUNITY IN PRIMARY CARE

Mukerjee M 1,2 , Willard-Grace R 2

1 UCD School of Medicine, University College Dublin, Ireland

2 Center for Excellence in Primary Care, Department of Family and Community Medicine, University of California, San Francisco, CA, USA

Scales measuring meaning and community in work are often long and lack specific healthcare context. We introduce novel measures of meaning and community as measures of work experience (WE) and explore their association with other measures of WE.

We used a survey of 295 clinicians and 479 staff members from primary care clinics in San Francisco (2021) to study correlations of our measures of meaning with items from the validated Work and Meaning Inventory (WAMI) [1], as well as other work experience measures such as burnout, and engagement. We used bivariate analysis, linear regression for associations between the novel measures, and other measures of WE. Mediation was tested using Sobel test.

The single item measure of meaning was weakly associated with items from the WAMI scale with significant correlations found in clinicians with WAMI 1 (r=.174; p=.032) and in staff with both WAMI1(r=.216; p<.001) and WAMI2 (r=.248; p<.001). Additionally, the items from the WAMI scale showed stronger associations with measures of burnout like cynicism and exhaustion (Maslach’s Burnout Inventory) [2] , single item burnout measure (Mini Z survey) [3] , and measures of engagement [4] . Both items of the community measure were associated positively with engagement and negatively with burnout, to a lesser degree. Notably, getting support for patient-related problems and recommending the clinic as a place to work (engagement) in staff yielded a significant unstandardized β=1.511 (p<.001).

The single item measure of meaning was outperformed by WAMI items. Community had strong associations with other measures of WE like engagement and leadership, especially for staff.

Reference

Steger MF, Dik BJ, Duffy RD. Measuring meaningful work: The work and meaning inventory (WAMI). Journal of career Assessment. 2012 Aug;20(3):322-37

Presenting Author: Monjori Mukerjee

Supervisor: Dr Rachel Willard-Grace

BUILDING A REGISTRY FOR SETD2 NEURODEVELOPMENTAL DISORDER

Wipf N 1 , Rabin R 2 , Pappas J 2

1 UCD School of Medicine, University College Dublin, Ireland

2 NYU Pediatrics, New York University, Langone, New York City, New York, USA

The SET domain containing 2 (SETD2) gene codes for a histone methyltransferase that mediates tri-methylation of the histone H3-lysine 36 residue (H3K36me3). Pathogenic variants in SETD2 were initially identified through studies of children diagnosed with autism spectrum disorder (ASD) and later associated with Luscan-Lumish syndrome (LLS). As more cases were identified, the phenotypic spectrum expanded to include SETD2 -neurodevelopmental disorders (NDD) with or without macrocephaly/overgrowth. Identification of more affected individuals will allow for further of specific SETD2 variants.

The initial drafting of the ethics proposal required a literature review, drafting of protocol, and establishing of a database. Documents included recruitment text, e-consent forms, addendums for cognitively impaired children, and a timeline. A HIPAA-secured RedCap database was built with the approved material. Once approved, individuals from a LLS social media group were contacted for recruitment to the study. A planned 50 individuals are to be involved.

Currently, the database is functional and participant’s responses are actively being collected. The database presently houses complete descriptions of features and medical records for three subjects, with two more in the process. Preliminary analysis revealed one individual from each category: SETD2-NDD with MCA, SETD2-NDD without macrocephaly, and an individual with mild neurodevelopmental presentation. Interestingly, the later individual has a nonsense variant in SETD2 , which hasn’t previously been observed.

With further growth and analysis of the database, a more concise genotype-phenotype criteria differentiating SETD2 conditions will be attained.

References

Edmunds JW, Mahadevan LC, Clayton AL. Dynamic histone H3 methylation during gene induction: HYPB/SETD2 mediates all H3K36 trimethylation. The EMBO Journal. 2007;27(2):406–20.

Pappas J, Rabin R. SETD2 Neurodevelopmental Disorders [Internet]. Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJ, Gripp KW, et al., editors. PubMed. Seattle (WA): University of Washington, Seattle; 1993 [cited 2022 Aug 1]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK575927/#:~:text=SETD2%20neurodevelopmental%20disorders%20(SETD2-NDDs

Presenting author: Nicolas Wipf

Supervisor: Dr John Pappas

CHARACTERIZATION OF THE CPP SIGNAL DURING DECISION-MAKING TASKS

Williamson E 1 , Geuzebroek A 2 , Kelly S 2

1 UCD School of Medicine, University College Dublin, Ireland

2 UCD School of Electrical and Electronic Engineering, University College Dublin, Ireland

Decision-making involves two key components: the encoding of the momentary evidence and its accumulation as the decision variable [1]. The centro-parietal positivity (CPP) is a decision variable signal characterized by an evidence-related buildup and decision-aligned peak, and dynamics consistent with evidence accumulation even in the absence of action and motor preparation signals [2]. Thus far, CPP experiments have used stimuli with static properties and no information leak. The purpose of the present experiment is to explore dynamically changing stimuli, and test the hypothesis that the amount of decision-making evidence leaked is greater in conditions where the subject must report the most recent state of the stimulus (the “last” condition) instead of the aggregate state averaged over all time (the “overall” condition).

The target participant group included adults not presenting with any neurological or psychiatric disorders. In a repeated measures design, the participants completed a task in which they were required to determine the overall or final direction (left or right) of a moving-dots stimulus after viewing it for a variable period containing random reversals. Electroencephalography (EEG) and button-press data were then analyzed using the eeglab toolbox for MATLAB R2022a.

Evidence accumulating over time in the CPP signal provided a steeper slope (µV/m 2 ) in the “overall” condition compared to in the “last” condition.

The results further support the CPP as a representation of evidence accumulation and show that more information was leaked in the “last” condition, as the amplitude corresponding to evidence was always lower during the time of evidence accumulation.

Acknowledgements

The author would like to acknowledge funding from the Wellcome Trust.

References

O'Connell RG, Dockree PM, Kelly SP. A supramodal accumulation-to-bound signal that determines perceptual decisions in humans. Nat Neurosci. 2012;15(12):1729-1735.

O'Connell RG, Kelly SP. Neurophysiology of human perceptual decision-making. Annu Rev Neurosci. 2021;44:495-516.

Presenting Author: Elizabeth Williamson

Supervisor: Assoc Prof Simon Kelly

INVESTIGATING THE IMPACT OF MORNINGNESS & EVENING TRAITS ON OBJECTIVE IN-LABORATORY SLEEP PARAMETERS

Colelli DR 1,2 , Dela Cruz G 2 , Murray BJ 2-4 , Boulos MI 2,4

1 UCD School of Medicine, University College Dublin, Ireland

2 Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada

3 Department of Medicine, Division of Neurology, University of Toronto, Toronto, Ontario, Canada

4 Sleep Laboratory, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada

Morningness-eveningness preference, also known as chronotype, is the tendency for a person to complete activities and sleep during certain hours of the day, and is categorized into morning and evening types. In-laboratory polysomnography (iPSG) is the gold-standard to assess sleep, however, an individual’s chronotype is not accounted for in current iPSG protocols, which may confound collected sleep data. The objective of our study was to assess if chronotype had an impact on sleep physiology during iPSG.

Patients who completed diagnostic iPSG and the Morningness-Eveningness Questionnaire (MEQ) during 2010-2015 were retrospectively analysed. The MEQ categorizes patients into morning type, evening type, or neither type. Multivariable linear regression models were used to assess if chronotype was associated with sleep quality, duration and physiology during iPSG.

The study sample included 2,612 patients (mean age of 53.6 years, 48% male) who completed iPSG and the MEQ. Morning type, compared to neither type, was significantly associated with an increase in total sleep time and rapid eye movement (REM) sleep, and decrease in sleep onset latency and the arousal index. Evening type compared to neither type was associated with a decrease in total sleep time, sleep efficiency, and REM sleep, and an increase in sleep onset latency and wake after sleep onset.

A morningness chronotype was associated with favourable sleep quality and duration while an eveningness chronotype was associated with poorer sleep quality. Current iPSG protocols should consider chronotype during a patient’s visit to the sleep laboratory as it may impact the recorded sleep metrics.

Presenting Author: David Colelli

Supervisor: Dr Mark Boulos

A 3D PRINTED TRAINING MODEL FOR CHOLECYSTECTOMY INCORPORATING THE ‘‘MOYNIHAN HUMP’’ ORIGIN OF THE CYSTIC ARTERY

Singaravelu A 1 , Myles C 1 , Gorman Singaravelu A 1 , Myles C 1 , Gorman L 1 , Campbell T 1 , Brougham DF 2 , Jones JFX 1

1 UCD School of Medicine, University College Dublin, Ireland

2 UCD School of Chemistry, University College Dublin, Ireland

Cholecystectomy, a very common surgery, is still associated with bile duct and vascular injury. The main aim of this study was to create a silicone molded training model for cholecystectomy with an unusual ‘‘Moynihan hump’’ vascular variant of the right hepatic artery. Silicone models offer excellent biomechanical properties for surgical simulation [1]; however, due to their hydrophobic nature, they have limited wetting-based applications, for example, adherence to hydrophilic substances and hydrographic sheets.

All 3D objects were sculpted in Blender 2.90 with reference to anatomical atlases and published literature. Polyvinyl alcohol (PVA) printed molds were pressure injected with silicone (shore 10A) [2] before dissolving the PVA support. Silicone models were immersed in a 3 mg/ml dopamine solution (37 °C, pH 8.5, 20 hours). Water contact angles of silicone samples were measured by the sessile drop method. Unpaired Student’s t test was used to compare the mean water contact angle of untreated and treated silicone samples. Conductive PVA mixed with 10mM phosphate buffered saline solution and activator (Elmer’s magical liquid) was used to simulate electrically conductive connective tissue and peritoneum.

A high-fidelity, diathermable model with key anatomical landmarks was created. Polydopamine coating significantly changed the water contact angle from 102 ± 2° to 86 ± 2° (p=3.6 x 10 -05 ) and improved hydrographic sheet adherence to the silicone models.

This model offers realistic surgical training in cholecystectomy and exposure to challenging anatomical variants.

Acknowledgements

The authors would like to thank Mr. Patrick Waldron from UCD School of Chemistry for his support on KRŰSS-SCIENTIFIC DSA25E goniometer.

References

Fletcher J*, Myles C*, Miskovic D, Jones JFX, Cahill R. Note * corresponds to joint first authors. Patient Specific Digital Modelling and 3D Printing of Abdominal Anatomy- The Next Frontier in Surgical Simulation? ASiT and MedAll Surgical Summit 2020. British Journal of Surgery, Volume 108, Issue Supplement_2, May 2021, znab134.027

Myles C, Cahill R, Jones JFX. Human Cadaver-specific 3D printing of abdominal anatomy. Anatomical Society Summer Meeting Glasgow 2021: Cutting Edge Anatomy. Journal of Anatomy 24 Nov 2021

Myles C, Cahill R, Jones JFX. Human Cadaver-specific 3D printing of abdominal anatomy. Anatomical Society Summer Meeting Glasgow 2021: Cutting Edge Anatomy. Journal of Anatomy 24 Nov 2021

Presenting Author: Ashokkumar Singaravelu

Supervisor: Prof James Jones

AN ANALYSIS OF COMPASSIONATE ACCESS PROGRAM FOR NEW ONCOLOGY DRUGS

Kelly S 1 , Zameer M 2 , Brown J 2 , Johnston G 2 , Adams, R 2 , Murphy D 2 , Kelly D 2 , Darwish W 2 , McCaffery J 2 , Duffy AG 1,2

1 UCD School of Medicine, University College Dublin, Ireland

2 Mater Misericordiae University Hospital, Dublin, Ireland

Irish cancer patients experience amongst the longest European waiting times for access to novel medications [1]. Compassionate access programs provide patients with such unavailable drugs, bridging the gap between efficacy and accessibility. The objectives of this study were to characterise the patient cohort under compassionate schemes at The Mater and quantify the degree of benefit or lack of benefit experienced.

A clinical audit approach was employed with purposive sampling utilised. Predefined data variables were collected retrospectively via Patient Centre and CATO ® software, with explicit coding processes employed. Descriptive analyses were performed, along with appropriate bivariate procedures. “Clinical Benefit” was defined as a radiological complete, partial or stable response to treatment.

113 patients were included in the study; median age 65 (29-94; M:F 55:45). N=93 received at least one dose of treatment, with 16 treatments utilised. Treatment duration ranged from 0-112 months, with 12 patients on treatment for >2 years. N=47 (42%) experienced a Clinical Benefit. N=7 experienced a complete response [CR]; with N=6 exhibiting a sustained CR. N=31 experienced a partial response and N=9 experienced stable disease. N=30 (27%) did not receive a planned treatment, or died within 3 months of treatment.

In our compassionate access program review, a significant proportion (42%) derived benefit. However, 27% did not receive a planned treatment due to clinical progression, or died within 3 months of treatment; suggesting availability came too late in their treatment course. While compassionate access programs can provide meaningful benefit, they are not a substitute for timely approval of novel agents.

Acknowledgements

The author would like to acknowledge the help of both Dr Austin Duffy and Dr Mohammed Zameer throughout the research process, along with all staff involved in the Oncology department of the Mater hospital.

Reference

Newton M, Scott K, Troein P. European Federation of Pharmaceutical Industries and Associations Patients W.A.I.T Indicator 2021 Survey. Brussels: IQVIA; 06 April 2022. 56 p. Report no.: 4

Presenting Author:Sarah Kelly

Supervisor:Assoc Prof Austin Duffy

ASSESSING THE IMPACT OF ORAL LIPID PRE-LOAD ON GLUCOSE TOLERANCE: A SINGLE SUBJECT, REPEATED MEASURES STUDY

Alqallaf A 1 , Swan P 2 , Docherty NG 2

1 UCD School of Medicine, University College Dublin, Ireland

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

Insulin resistance (IR) is a long-studied topic with complex mechanisms yet to be unravelled. Studies have shown that an intravenous lipid load can alter long-term glucose tolerance by inducing IR. However, acute alteration of glucose tolerance by lipid has been scarcely studied (1). Current results may provide foundation for a large-scale study to further investigate molecular mechanisms.

A single participant was studied over 3-blocks, each consisting of two oral glucose tolerance tests (OGTT) conducted over a 3-day period. In each block, the participant presented with a 15-16 hour overnight fast for the first visit (Day C). On the second visit (Day L) the participant would ingest a weight-adjusted lipid emulsion (1g/kg) 6-8 hours prior to their visit. A 0-minute spot urine and 120-minute urinary output were collected to calculate diuresis.

Oral Lipid pre-load did not alter summary measures of glucose tolerance in a healthy participant. However, an apparent trend for an earlier peak and a lower nadir in blood glucose post-OGTT in addition to a relative increase in diuresis were observed. Mean values ± standard deviations are mentioned in the table below.

This suggests that overall insulin excretion may have been higher following oral lipid challenge and the increase in diuresis therein could be related to this. Subsequent studies will assess the kinetics and profile of urinary excretion of sodium and C-peptide for further investigations.

Reference

Roden M, Krssak M, Stingl H, Gruber S, Hofer A, Fürnsinn C, et al.. Rapid impairment of skeletal muscle glucose transport/phosphorylation by free fatty acids in humans. Diabetes 1999;48(2):358–64.

Presenting Author: Alrataj A S M Alqallaf

Supervisor: Assoc Prof Neil Docherty

EP4 DELETION AND ATHEROSCLEROTIC BURDEN IN PD-1 DEFICIENT HYPERLIPIDAEMIC MICE

Thomas M 1,2 , Tang SY 2,3,4 , Lordan R 2,3,4 , McCreery C 1,2 , Ghosh S 2,3,4 , Skarke C 2,3,4 , FitzGerald GA 2,3,4 .

1 UCD School of Medicine, University College Dublin, Ireland

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

3 Perelman School of Medicine, Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA

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

Immune-checkpoint inhibitors (ICI) have revolutionised cancer therapy but accelerate atherogenesis and attendant sequelae(1)(2). Prostaglandin-E 2 potentiates atherogenesis and PD-L1 expression, possibly via the EP4 receptor (EP4R), antagonists of which are currently in clinical trials. We sought to characterise the effect of EP4R knock out (KO) on atherosclerotic burden (AB) in a murine model of ICI-therapy in high cardiovascular-risk patients.

IndCre Ep4r fl/fl , Ldlr -/- , Pd-1 -/- mice were generated and Cre-negative littermates used as controls. Mice (n=3) were fed high-fat diet (HFD) for 12 weeks with systolic blood pressure (SBP) and heart rate (HR) measured daily at week 12 via a non-invasive tail-cuff system. AB was determined by estimation of lesion surface area in Sudan-IV stained aortae. Total splenic, myocardial, and renal medulla RNA was extracted and relative gene expression determined by RT-qPCR. Systemic prostaglandin biosynthesis was assessed by mass spectrometric analysis of urinary prostaglandin metabolites in pooled urine samples. Plasma glucose, LDL, and triglycerides were measured by commercial assays.

EP4R significantly decreased AB relative to controls (8.6%±2.1 vs 26.4%±20 p<0.05). HFD increased urinary prostacyclin and thromboxane metabolites at 12 weeks in both cohorts, reflective of increased platelet-vessel wall interactions. KOs showed compensatory increase in PGE-M. Non-significant trends of decreased plasma LDL and increased plasma triglycerides were observed in KO mice. No differences were noted between cohorts in weight gain, SBP, HR, plasma glucose, nor splenic, myocardial, and renal medullary inflammatory gene expression ( Cox -1, Cox- 2, Ptges , Ptges-2 , Cd274 , Myh6 , Cd68 , Fap ).

EP4R deletion decreases AB without altering inflammatory gene expression, suggesting EP4R inhibition may blunt atherogenesis during ICI. Larger studies are necessary to confirm this possibility.

Acknowledgements

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

References

Calabretta R, Hoeller C, Pichler V, Mitterhauser M, Karanikas G, Haug A, et al. Immune Checkpoint Inhibitor Therapy Induces Inflammatory Activity in Large Arteries. Circulation. 2020 Dec 15;142(24):2396–8.

Drobni ZD, Alvi RM, Taron J, Zafar A, Murphy SP, Rambarat PK, et al. Association Between Immune Checkpoint Inhibitors With Cardiovascular Events and Atherosclerotic Plaque. Circulation. 2020 Dec 15;142(24):2299–311.

Presenting Author: Matthew Thomas

Supervisor: Prof Garret A. FitzGerald

Co-Supervisor: Dr Soon Yew Tang

THE TIMING OF BMAL1 DELETION DIFFERENTIALLY IMPACTS SKELETAL MUSCLE MASS REGULATION

McCreery C 1,2 , Lordan R 2,3,4 , Thomas M 1,2 , Teegarden SL 2,3,4 , Tang SY 2,3,4 , Skarke C 2,3,4 FitzGerald GA 2,3,4

1 UCD School of Medicine, University College Dublin, Ireland

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

3 Perelman School of Medicine, Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA.

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

Daily rhythmic gene expression is orchestrated by the core clock genes Bmal1 and Clock . Dysregulation of the clock is risk factor for sarcopenia in humans. Embryonic knockout of Bmal1 (eKO) in mice leads to an accelerated aging phenotype in muscle not observed in postnatal inducible deletion of Bmal1 (iKO) (1). We investigated the timing of Bmal1 and the role of the molecular clock in muscle mass regulation in both sedentary and endurance exercise-trained mice to characterize the differences in Bmal1 KO models. A greater quantity of small muscle fibers (500-750 µm 2 ) signifying atrophy were present in eKO muscle versus their respective controls, whereas iKO muscles are morphologically similar to control mice. Sedentary eKO mice have reduced grip strength versus control mice, whereas iKO mice show no difference in muscle function. Trim63 , a critical regulator of muscle atrophy, was similarly elevated in exercised iKO mice and controls as determined by RT-qPCR in the gastrocnemius. However, Trim63 was elevated to a greater extent in exercise-trained eKO mice versus exercised controls, suggesting increased atrophy. Fbxo32 and Fbxo21, additional atrophy regulators, were also differentially expressed post-exercise in the eKO mice versus littermate controls but not in the iKOs. Genes responsible for protein synthesis ( Eif4g3 and Akt1 ) and proteasome regulation ( Psmc3, Psmc4 , and Psmd11 ) were not altered across all cohorts. Collectively, these findings demonstrate that embryonic deletion of Bmal1 leads to an atrophic muscle phenotype evoked by exercise and likely mediated by Trim63 with loss of function. This not observed in postnatal deletion possibly due to a clock independent function of Bmal1 in development. These findings may lead to the identification of therapeutic targets of atrophy associated with deconsolidation of the clock in ageing.

Acknowledgements

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

Reference

Schiaffino S, Blaauw B, Dyar KA. The functional significance of the skeletal muscle clock: lessons from Bmal1 knockout models. Skeletal muscle. 2016 Dec;6 (1):1-9.

Presenting Author: Charlotte McCreery

Supervisor: Prof Garret A. FitzGerald

Co- Supervisor: Dr Ronan Lordan

CHARACTERIZING HIP JOINT KINEMATICS AND DETERMINING FEMORAL HEAD TRANSLATION VECTORS THROUGH ANALYSIS OF UPRIGHT OPEN MRI IMAGES

Sohirad S 2,3 , Zhang H 2 , Wilson D 1,2

1 Department of Orthopaedics, University of British Columbia, Vancouver, Canada

2 Centre for Hip Health and Mobility, Vancouver, British Colombia, Canada

3 UCD School of Medicine, University College Dublin, Ireland

Upright open MRI machines allow for the taking of images with individuals placed in various positions that deviate from the standard supine. Hip joint kinematics can be characterized through their use by analysing and comparing images taken from the hip joint in different degrees and combinations of flexion/extension/adduction/abduction/rotation.

In this study a high-fidelity image using a standard closed 3T MRI of a relaxed hip joint in a neutral supine position, and images using a 1.5T upright open MRI with the hip in the same position and 90° of flexion were taken. From the high-fidelity image an accurate 3D computer model of the pelvis and proximal femur was generated. These models were then registered in 3D space to the exact positions of the femur and pelvis as determined in the images taken using the open MRI. Through the development of a custom image processing algorithm, the translation vector between the centres of the femoral head and acetabular cup was then derived.

A comprehensive array of these femoral head translation vectors for the hip in all positions fully determines the kinematics of the joint. Currently, the only calculated vector is for the hip joint at 90°of flexion, being [0.7777,-0.3847,0.1158]mm based on the coordinate system of the International Society of Biomechanics 1 (1).

Characterization of hip joint kinematics is particularly important for the understanding of how labrum damage and osteoarthritis develop in people with cam and pincer deformities by giving insight into which areas are at greatest risk for impingement

Reference

ISB recommendation on definitions of joint coordinate system of various joints for the reporting of human joint motion--part I: ankle, hip, and spine. International Society of Biomechanics. Wu, Ge, et al. 4, s.l. : Journal of Biomechanics, April 2002, Vol. 35, pp. 543-8. 11934426.

Presenting Author: Sahand Sohirad

Supervisor: Dr David Wilson

A COORDINATE REGRESSION-BASED DEEP LEARNING MODEL FOR CATHETER TRACKING IN CARDIAC INTERVENTIONS

Rashid M 1 , Mosadegh B 2

1 UCD School of Medicine, University College Dublin, Ireland

2 Department of Radiology, Weill Cornell Medical College, New York City, New York, USA

More than a million minimally invasive percutaneous cardiac procedures are conducted every year to repair structural heart defects. The present study aims to demonstrate the utility and safety of image guidance through a mixed-reality headset.

This goal will be accomplished by recording the accuracy to which the novel imaging program can track a catheter during left atrial appendage, patent foramen ovale or atrial septal defect repair operations. The sample size will consist of 30 patients who are already enrolled in these procedures. Intraprocedural vitals will be recorded using respiratory and ECG monitors and all fluoroscopic images will be processed by the program. During the procedure, monoplane fluoroscopy will be utilised and once the delivery sheath is within the target, bi-plane fluoroscopy will be used to validate the monoplane coordinate predictions. A positive result is recorded if fluoroscopy and the imaging program both indicate that the catheter is in the correct position. A post study questionnaire then will assess the physicians experience with the added monitors and whether they interfered with the operation.

As this study is still in the early phases, ethical approval is being acquired to attach the bio-monitors. We expect to prove that the program allows for accurate and safe determination of catheter positioning. The benefit and implications that the findings of this study may provide is that the imaging system has the potential to greatly improve the accuracy of transcatheter cardiac procedures and potentially expand its utility to a diverse array of catheter-based operations.

Presenting Author:Muaz Rashid

Supervisor:Assoc Prof Bobak Mosadegh

QUALITY OF LIFE OUTCOMES OF 400 PATIENTS TREATED WITH STAGE IIIC PROSTATE CANCER

Forbes E 1 , Cesaretti J 2

1 UCD School of Medicine, University College Dublin, Ireland

2 Florida Physician Specialists, Jacksonville, Florida USA

High-risk prostate cancer is a lethal malignancy. This research studied a uniquely large cadre of Stage IIIC patients. Stage IIIC is uncommon and until now avoided scrutiny. This opportunity prompted evaluating multiple aspects of these patients’ characteristics and management.

Our study cohort consisted of 429 patients (median age: 70) treated at Terk Oncology, Jacksonville, Florida, between 1997-2021 with Gleason grade 5. Patient characteristics such as smoking, age, race, and history were tabulated de-identified. Pathology, treatment, and outcomes were recorded similarly. Averages and medians were used for the statistical analysis.

The incidence of IIIC cases decreased 34.8% after 2012 and rebounded 82.6% after 2015, compared to 4.5% and 3.8% respectively for all comers excluding IIIC. For IIIC, 100 patients (25.4%) had a family history of prostate cancer, 191 (44.52%) had a pre-treatment prostate-specific antigen (PSA) level of ≥ 10 ng/mL, and 90.2% had T1-T2 disease. 77 patients developed distal failure; 50 had perineural invasion (PNI). 7 patients developed local failure; 6/7 had PNI. The change in International Prostate Symptom Score (IPSS) after radiation treatment was 2.08 ± 6.19.

Stage IIIC patients have a high incidence of prostate cancer in relatives, and high PSA but not bulky disease. Radiotherapy has only minor effect on the patient’s IPSS. PNI is a strong risk factor for recurrence- predominantly distant. PSA screening in America was discouraged for 4 years after 2012. The rebound of cases after 2016 implies that lack of screening allowed undiagnosed disease to progress to high grade, and emphasizes the importance of screening.

Presenting Author: Erica Forbes

Suervisor: Dr Jamie Cesaretti

DESCRIPTION OF THE CHANGES IN PROFILES AND PATTERNS OF CANCER AMONG ELDERLY PATIENTS AT HOSPICE AFRICA UGANDA

Akinola O 1 , Mwebasa E 2

1 UCD School of Medicine, University College Dublin, Ireland

2 Hospice Africa Uganda, Kampala, Uganda

Uganda’s population has grown from 19.2 million in 1993 to 48.1 million in 2022 [1], and the proportion aged over 60 is increasing [2]. Uganda’s cancer epidemiology may have changed due to alteration in causative or associated factors, for example increased coverage of vaccines against human papilloma virus (HPV) [3].

This retrospective cross-sectional study aimed to describe changes in the profiles and patterns of cancer amongst the elderly patients (60 years and above) seen at Hospice Africa Uganda (HAU). Patient data was mined from the organisation database from 1993-2021 to identify the most common cancers and their trends over time.

The most common cancers were prostate cancer for males (38.6%) and cervical cancer (19.2% of patients) for females. The proportion of patients with prostate cancer increased from 10.6% (n=104) to 22.5% (n=542) between the years 1993-1995 and 2017-2019. The proportion of patients with cervical cancer increased from 9.6% (n=104) to 14.4% (n=542) within the same period. Prostate cancer is one of the most common cancers among elderly males globally [4] while cervical cancer, which is associated with HPV infection may be highly prevalent in this patient group because of low HPV vaccine coverage [3] coupled with increased capacity to screen for and diagnose this malignancy in Uganda [5].

For these 2 most prevalent cancers, a secondary analysis of 64 patients showed pain and symptoms as the commonest reason for referral to HAU, while 63% reported their goal of care was symptom control. For these patients, comprehensive control of symptoms was the intervention which resulted in improved quality of life.

References

The Worldometer, 2021 [URL: https://www.worldometers.info/world-population/uganda-population/?app=true ]

UBOS, & ICF International. (2012). Uganda demographic and health survey 2011. Kampala: Uganda UBOS & ICF International. [URL: https://dhsprogram.com/publications/publication-fr264-dhs-final-reports.cfm .]

Isabirye, A., Mbonye, M., Asiimwe, J.B. et al. Factors associated with HPV vaccination uptake in Uganda: a multi-level analysis. BMC Women's Health 20, 145 (2020). 10.1186/s12905-020-01014-5

Worldwide cancer data | World Cancer Research Fund International [Internet]. WCRF International. 2022 [cited 9 August 2022]. Available from: https://www.wcrf.org/cancer-trends/worldwide-cancer-data/#:~:text=Breast%20and%20lung%20cancers%20were,contributing%2010.7%25%20of%20new%20cases .

Nakisige C, Schwartz M, Ndira A. Cervical cancer screening and treatment in Uganda. Gynecologic Oncology Reports. 2017;20:37-40.

Presenting Author: Oluwaseyi Akinola

Suervisor: Dr Eddie Mwebesa

A RETROSPECTIVE ASSESSMENT OF THE SPIRITUAL NEEDS AND THEIR PREVALENCE AMONGST PALLIATIVE CARE PATIENTS AT HOSPICE AFRICA UGANDA

Renner C 1 , Natuhwera G 2

1 UCD School of Medicine, University College Dublin, Ireland

2 Hospice Africa Uganda, Kampala, Uganda

There is increasing research supporting the importance of spiritual care within palliative care (PC). However, this research is sparse in low-income countries (LICs). This study sought to document the prevalence of spiritual needs among cancer patients receiving PC at Hospice Africa Uganda (HAU).

107 randomly sampled case notes of cancer patients were reviewed. Data was collected using a tri-categorical questionnaire based on HAU and the HOPE spiritual needs assessment tools. Data was entered, coded and analyzed in excel. Statistical analysis performed included single factor ANOVA and two-sample T-tests, using a 5% significance level. P-values less than 0.05 were considered statistically significant.

Data were organized into three categories-: organized religion (OR), personal spirituality (PS), and personal implications (PI). Majority (70%) were female. Regarding diagnosis, 64.5% had cancer, 18.7% had cancer and HIV/AIDS, and 12.2% had cancer and other comorbidities. 99% of the patients considered religion important, 97% prayed and 98% found prayer helpful. Spiritual practices had positive effects-: better sleep, maintaining hope, peace and comfort, and practical support. 13.6% of patients reported changing religion, usually in a search for healing. Inability to receive sacraments and congregate for prayers were identified as common causes of spiritual distress. The mean comparison tests point to an association between the patient’s gender and presenting with unrelieved pain, p-value (0.044), α (0.05). Frequency data indicated that males may be at a higher risk of experiencing unrelieved pain than females (87% versus 68%).

This study demonstrated the importance of maintaining and facilitating fulfillment of spiritual needs within holistic PC, and also the pressing need to address unrelieved pain and psychological problems which are potential catalysts for spiritual distress.

Persenting Author:Carl Renner

Supervisor: Dr Germans Natuhwera

A RETROSPECTIVE STUDY ON CHANGING PATTERNS OF CANCER DIAGNOSIS AMONG ADULT FEMALES AT HOSPICE AFRICA UGANDA, MBARARA

Goubkine D 1 , Birungi AD 2

1 UCD School of Medicine, University College Dublin, Ireland

2 Clinical Department, Hospice Africa Uganda, Makindye Division, Kampala, Uganda

Hospice Africa Uganda (HAU) is a palliative care organisation which provides essential cancer palliation to the community in which it resides. Currently, the burden of female cancer is a grand unmet challenge in African healthcare where female patients receive marginalized care and face worse outcomes from infection-related cancers. 1  ​ 2 Cancer research focused primarily on females results in data which allows for provisional targeted care. The aim of this review, spanning across 25 years, was to identify cancer prevalence and report on trends among HAU’s female patients at the Mbarara site.

This study was a retrospective chart inquiry, sampling all records of female patients over the age of 18 with a positive cancer diagnosis (n=13,646) from 1995 to 2020. Data was analyzed for each five-year interval and then cross referenced to represent the progression. Data showed that over the 25-year period there were six cancer types that remained among the top five most diagnosed cancers among hospice patients (n=9615): Cervical, breast, Kaposi sarcoma, upper gastrointestinal (esophageal and stomach), lower gastrointestinal (colon, rectal, anal) and hepatocellular carcinoma. Cervical cancer prevailed as the most common cancer making up an average of 43% of the overall prevalence of the top 6 cancers between 1995 and 2020. While breast cancer (21%) followed a close second. Together cervical and breast cancer made up an average 64.3% of the top 6 cancers over the time frame. The trends described in this study provide a brief outlook into where female cancer will go in the future for Hospice Africa Uganda. This study has important implications for the building of a more targeted health service infrastructure of cancer management in the region. Further studies are imperative for detailing the pattern between infection and female cancers and whether the next decade will see the decline of vaccine-mediated cancers in the area.

Acknowledgments

This project was supported financially by University College Dublin School of Medicine.

Reference

Arbyn, Marc et al. Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis. The Lancet Global Health, Volume 8, Issue 2, e191 - e203

Obol, J.H., Lin, S., Obwolo, M.J. et al. Knowledge, attitudes, and practice of cervical cancer prevention among health workers in rural health centres of Northern Uganda. BMC Cancer 21, 110 (2021).

Presenting Author: Dasha Goubkine

Supervisor: Dr Agasha D. Birungi

THE SURVIVAL OF CERVICAL CANCER PATIENTS AT HOSPICE AFRICA UGANDA

Fogarty J 1 , Adong Olet D 2 , Nalubega H 2

1 UCD School of Medicine, University College Dublin, Ireland

2 Hospice Africa Uganda, Kampala, Uganda

The objective of this project is to describe the survival of cervical cancer patients at Hospice Africa Uganda (HAU).

A retrospective study of the case notes of patients with a diagnosis of cervical cancer was carried out. 75 case notes were selected using purposive sampling, reduced to a sample size of 63 by removing data which didn’t fit the inclusion criteria. The case notes were from patients with confirmed cervical cancer diagnoses who presented/were admitted to HAU from 1993 to 2022. HAU introduced the Road to Care Programme in 2012, endeavouring to improve access to cancer treatments including radiotherapy. This study aims to investigate the impact of the Road to Care programme by comparing survival of patients from before and after 2012 in a descriptive analysis.

There is a correlation between survival and the stage of cervical cancer of the patient at admission to HAU. All patients in the study who had died at last contact with HAU had either stage 3 or 4 cervical cancer. 31 patients had stage 3B, 4A or 4B cervical cancer, and 6 died (19.35%, n=31). All of these patients were admitted to HAU before 2012. Of all patients admitted to HAU before 2012, 7 died (24.14%, n=34). Of all patients admitted to HAU after 2012, 1 died (3.45%, n=29).

These results indicate an increase in survival among patients at HAU in the period after 2012, suggesting that the Road to Care Programme was beneficial.

Results of survival estimates are to follow and will be calculated using Kaplan-Meier curves.

Acknowledgements

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

Presenting Author: Jennifer Fogarty

Supervisor: Dr Dorothy Olet Adong

Co-Supervisor: Ms Harriet Nalubega

EFFECTS OF TIMING OF CALORIC INTAKE ON WEIGHT LOSS

Chen K 1 , Bai D 2

1 UCD School of Medicine, University College Dublin, Ireland

2 Lifestyle LLC, Seattle, Washington, USA

Weight control is a prominent recommendation in many aspects of healthcare. Timing of caloric intake represents a target to help control weight. The aim of this research is to (a) evaluate the evidence supporting when a majority of calories should be consumed and (b) identify considerations for new research opportunities to maximize weight loss.

This study was designed as a non-systematic literature review. Various key words/terms were used as inclusion criteria such as “meal” “timing” “ghrelin” “diet” “circadian rhythm”. The main exclusion criteria was avoidance of an overemphasis on the duration of fasting.

All recent studies have shown to agree that consuming more calories during “breakfast” is shown to be associated with the largest reduction in BMI in isocaloric diets. Various explanations for the weight loss have been proposed such as energy efficiency such as heat generation; metabolic processes such as glucose tolerance; and reduced hunger levels. Further studies have shown that irregular eating schedules can promote weight gain.

The projected results of the ongoing study support popular trends to strive to consume a larger portion of calories earlier; however, the broad usage of the terms breakfast, lunch, and dinner are identified as a limiting factor in studies. Future studies should be pursued and monitored in relationship to both absolute timing as well as relative timing in relationship to when individuals wake up. Additional studies are needed to be designed to understand an individual success chance and risk while making adjustments to shift to earlier calorie consumption.

Presenting Author:Kevin Chen

Supervisor:Dr Diane Bai

TRANSFORMING INTRAOPERATIVE BREAST CANCER POST-MASTECTOMY INDOCYANINE GREEN ANGIOGRAMS INTO RELEVANT INPUT FOR PREDICTIVE MODELS

Jindal A 1, 2 , Dalli J 1, 2 , Nguyen CL 3, 4, 5 , Epperlein JP 6 , Warrier S 3, 4, 5 , Cahill RA 1,2

1 UCD School of Medicine, University College Dublin, Ireland

2 UCD Centre for Precision Surgery, School of Medicine, University College Dublin, Ireland

3 Department of Breast Surgery, Chris O’Brien Lifehouse, Camperdown, Australia

4 Department of General Surgery, Royal Prince Alfred Hospital, Camperdown, Australia

5 Department of Surgery, The University of Sydney, Camperdown, Australia.

6 IBM Research Europe, Dublin, Ireland

Advances in surgical near-infrared (NIR) cameras have allowed intraoperative use of indocyanine green fluorescence angiography (ICGFA) in breast cancer surgery for supplementary assessment of post-mastectomy skin flap perfusion, demonstrably reducing postoperative complication rates. Voluminous NIR recordings are ripe for computational interrogation, opening avenues to explore the role of artificial intelligence in developing surgical recommender systems. In this endeavour we aim to explore and parameterize a clinical case series of post-mastectomy NIR recordings into a dataset relevant for input into artificially intelligent algorithms.

Intraoperative post-mastectomy ICGFA videos from a retrospective case series collected at a single unit (2015 to 2022) within a clinical trial (Protocol X17-0359 HREC/17/RPAH/542) were obtained, organized, and visually assessed. Procedural data, patient demographics and postoperative outcomes were appended. Whole breast fluorescence time series data were extracted using a bespoke tracker/quantifier (IBM research) and arterial inflow milestones were extracted following annotation. Subsequently, machine learning (ML) algorithms were applied on an exploratory basis.

Recordings from patients (n=274 females) undergoing ICGFA, including primary and delayed (n=57) procedures were analysed. Videos with excessive movement, instrument intrusion, or missed inflow were discarded leaving 232 remaining (age range: 26-79 years, major complication rate: 10.3%). The digitized dataset was sufficiently robust to enable exploratory applications of ML algorithms yielding already promising results (sensitivity: 58.1%, specificity: 76.5%) for predicting postoperative complications.

Surgical video dataset curation is vital for developing artificially intelligent predictive models. This work achieved an acceptable standard for applying ML algorithms, encouraging further optimization and validation for intraoperative decision-support tools for cancer patients.

Disclosures

Prof Ronan A Cahill receives speaker fees from Stryker Corp, Olympus and Ethicon/J&J, research funding from Intuitive Corp and Medtronic and holds research funding from the Irish Government (DTIF) in collaboration with IBM Research in Ireland and from EU Horizon 2020 in collaboration with Palliare. Dr Jeffrey Dalli is employed as a researcher in the DTIF and is also a recipient of the TESS scholarship (Malta). Dr Jonathan P Epperlein is a full-time employee of IBM Research, a division of IBM, which provides technical products and services worldwide to government, healthcare, and life-sciences companies. Dr Chu Luan Nguyen and Sanjay Warrier report no disclosures.

Presenting Author:Abhinav Jindal

Supervisor:Prof Ronan A. Cahill

Co-Supervisor:Dr Jeffrey Dalli

INVESTIGATING EPIGENETIC PROTEIN COMPLEXES IN HIGH-RISK CHILDHOOD BLOOD CANCERS

Arnott C 1 , Bhattacharyya T 2 , Bond J 1, 2, 3

1 UCD School of Medicine, University College Dublin, Ireland

2 UCD Systems Biology Ireland, University College Dublin, Ireland

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

Polycomb repressive complex 2 (PRC2) is an epigenetic regulator of transcription. Genes encoding PRC2 factors are often mutated or deleted in childhood blood cancers and are linked to poor prognosis in paediatric acute myeloid leukaemia (AML).[1] We aimed to investigate these mutations’ impact on the complex.

We used a combination of computational tools that allow in silico prediction of PRC2 mutational effects on protein structure and function across AML and T-cell acute lymphoblastic leukaemia (T-ALL) cell lines. In-depth computational analysis of single nucleotide polymorphism in a PRC2 accessory component (AEBP2), seen in CCRF-CEM, a T-ALL cell line, and the resultant effect on its interaction with a PRC2 core protein (SUZ12) was investigated.[2] Molecular docking (HADDOCK webserver) was performed for both wild-type and mutant AEBP2 to SUZ12 wild-type, and Z-scores were calculated for the analysed clusters. Molecular dynamics simulations (GROMACS) were carried out for both complexes. To validate our in silico predictions, we performed immunoblotting of protein extracts from nine AML and four T-ALL cell lines, carrying differing PRC2 mutations (see table).

Our computational analysis indicates altered SUZ12-AEBP2 interactions in CCRF-CEM which carries mutant AEBP2, providing one example of affected complex structure (Z-scores = -1.6 (SUZ12-AEBP2 wild-type), -1.7 (SUZ12-AEBP2 mutant)). Overall, our analysis suggests that PRC2 mutations in patients can critically affect complex structure and function, impacting leukaemia biology.

Understanding PRC2 complex changes in childhood leukaemia reveals vulnerabilities, providing rational avenues for the development of new epigenetic-based cancer therapies which are increasingly being incorporated into clinical treatments.

References

Jones, L., McCarthy, P. and Bond, J. Epigenetics of paediatric acute myeloid leukaemia. Br J Haematol. 2020; 188: 63-76.

Chen S, Jiao L, Shubbar M, Yang X, Liu X. Unique Structural Platforms of Suz12 Dictate Distinct Classes of PRC2 for Chromatin Binding. 2018; 69(5): 840-52.

Chen S, Jiao L, Shubbar M, Yang X, Liu X. Unique Structural Platforms of Suz12 Dictate Distinct Classes of PRC2 for Chromatin Binding. 2018; 69(5): 840-52.

Presenting Author: Ceri Arnott

Supervisor: Prof Jonathan Bond

CLINICAL AND GENOMIC CHARACTERISTICS OF YOUNG PATIENTS WITH MULTIPLE MYELOMA

Saldarriaga M 1 , Sowa A 1,2 , Jayabalan D 3 , Rosenbaum C 1 , Pearse R 1 , Monge J 4 , Niesvizky R 1 , Bustoros M 1

1 Division of Hematology & Medical Oncology, Weill Cornell Medicine, New York Presbyterian Hospital, New York, NY, USA

2 UCD School of Medicine, University College Dublin, Ireland

3 Department of Pathology & Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA

4 Hematology & Medical Oncology, Weill Cornell Medical College/New York Presbyterian Hospital, New York, NY, USA

Multiple Myeloma (MM) is a plasma cell malignancy with a median age of 65-years at diagnosis. Within this study, we aim to understand the clinical characteristics and genomic drivers of young MM using the Weill Cornell/New York Presbyterian (WCM) and CoMMpass (MMRF) registries.

Using R Software (version 4.1), land-mark analysis was used to control time-dependent covariates within Kaplan Meier, Univariable, and Multivariable Cox proportional hazard models.

From the WCM registry, the <= 45-year group was enriched for individuals of African American descent (40% vs 10%, p = 0.04) and stage I ISS (51% vs 34%, p = 0.01). The median progression free survival (PFS) for each group was 7.92 years (95% CI 4.50 - NA) for the <= 45-year group and 3.25 years (95% CI 1.92 - 10.67) for the >45-year group. Within the MMRF study, the young group had similar trends as the WCM cohort plus a lower frequency of deletion 13q (35% vs 50%, p 0.03) and gain 1q (22% vs 42%, p < 0.01). DEA and GSEA showed a total of 1945 (3.5%) and 2164 (3.9%) over and under-expressed genes, with the young group being enriched for CD-1 transcriptional signatures (NES 1.86, adjusted p 0.028).

Young patients with MM have distinct clinical and demographic characteristics suggesting a potential role of genetic and environmental factors in early presentation. They also had a comparable to improved PFS than older patients potentially due to biologic drivers or factors related to patient age.

Presenting Author:Aubrie Sowa

Supervisor:Dr Mark Bustoros

Co-Supervisor:Dr Mateo Mejia Saldarriaga

HAND HYGIENE COMPLIANCE, BARRIERS AND OPPORTUNITIES ACROSS HEALTH CARE FACILITIES IN ARUSHA, TANZANIA

Picard R 1 , Mwandri M 2

1 UCD School of Medicine, University College Dublin, Ireland

2 Meru District Hospital, Arusha, Tanzania; Patandi Dispensary, Arusha, Tanzania

Infection transmission in healthcare facilities, known as Hospital Acquired Infections (HAI), play an enormous role in patient outcomes, hospital safety, and healthcare expenditures. Among the most cost-effective tools for controlling HAIs is hand hygiene [1]. Despite a high burden of HAIs in low- and middle-income countries, such as Tanzania, widespread use of hand hygiene practices has not been documented [2].

This study assessed hand hygiene compliance in community hospital and dispensary settings in Tanzania utilising quantitative and qualitative research methods. These included the WHO's Hand Hygiene Monitoring Tools as well as clinician focus group discussions. The study aimed to set a baseline on current hand hygiene standards in the facilities, with the goal of future improvement projects and subsequent assessment of the effectiveness of such interventions.

This research indicated that basic hand hygiene was not utilised in 91% of observed clinician-patient interactions. This is despite many of these clinicians displaying knowledge of hand hygiene, perceiving hand hygiene as high importance to patient outcomes, and having received formal hand hygiene training in the previous three years. During the observations with correct implementation, handwashing and hand rub were used at similar rates.

Although hand hygiene is a low cost and highly effective method to reduce HAIs, proper hand hygiene was chronically underutilised. The surveys, observations, and focus group indicated the greatest challenge was a severe lack of basic infrastructure. These findings are crucial to bring about quality improvement in the facilities’ hand hygiene, as well as for comparing healthcare facilities in Tanzania and beyond.

References

Habboush Y, Benham MD, Louie T, Noor A, Sprague RM. New York State Infection Control. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022. Available from: http://www.ncbi.nlm.nih.gov/books/NBK565864/

Allegranzi B, Gayet-Ageron A, Damani N, Bengaly L, McLaws ML, Moro ML, et al. Global implementation of WHO’s multimodal strategy for improvement of hand hygiene: a quasi-experimental study. The Lancet Infectious Diseases. 2013 Oct;13(10):843–51.

Presenting Author: Rachel Picard

Supervisor: Dr Michael Mwandri

REGULATION OF CXCL16 EXPRESSION IN DENDRITIC CELLS BY BACTERIA THAT COMMONLY COLONISE THE HUMAN RESPIRATORY TRACT

Alkanderi, AAHA 1 , Lalor, SJ 1

1 UCD School of Medicine, University College Dublin, Ireland

Increasing evidence indicates that myelin-reactive T cells traffic through the airways in the pre-clinical stages of experimental autoimmune encephalomyelitis (EAE), an animal model of Multiple Sclerosis. We have found that specific human respiratory tract bacteria including Moraxella catarrhalis and Klebsiella pneumoniae , but not Veillonella parvula , a bacterium commonly found in healthy human lungs, can promote pathogenicity in myelin-specific Th17 cells. This was associated with upregulated expression of the inflammatory chemoattractant molecule CXCL16 in the lungs of mice exposed to these bacteria as well as the recruitment of CXCR6-expressing Th17 cells to the lungs prior to their accumulation in the CNS. The cellular source of CXCL16 in response to bacterial stimulation is unknown.

We cultured murine bone marrow-derived dendritic cells (BMDC) for 10 days and confirmed their phenotype and maturation by flow cytometry, before exposing them to M.catarrhalis , K.pneumoniae and V.parvula . After 24 hours, we examined CXCL16 protein secretion in culture supernatants by ELISA and Cxcl16 gene expression by PCR.

We found that CXCL16 is constitutively produced by BMDC but were unable to detect any changes in chemokine concentration in cells following exposure to any bacterium. However, our data appeared to plateau, and future experiments will involve dilution of culture supernatants prior to ELISA. Nevertheless, we found that all three bacteria induced a dose-dependent increase in Cxcl16 gene expression, compared to untreated cells.

Our data indicates that bacteria colonising the human respiratory tract can promote CXCL16 expression in DC and may contribute to recruitment of pathogenic Th17 cells in inflammatory conditions.

Presenting Author: Amal Alkanderi

Supervisor: Dr Stephen Lalor

THERAPEUTIC TOOLS FOR SPINAL CORD INJURY: INVESTIGATING THE POLARISATION OF BV2 MICROGLIA IN 3% GELMA HYDROGELS

Costello L 1 , Walsh C 1, 2 , Dooley D 1, 2

1 UCD School of Medicine, University College Dublin, Ireland

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

Spinal Cord Injury (SCI) is very serious and debilitating condition that causes permanent motor and sensory dysfunction. There is currently no curative therapy available for SCI. Hydrogels are emerging as a promising drug delivery method as they can carry therapeutic factors and can be directly injected into the lesion site. By allowing for sustained therapeutic release, they can help modulate the neuroinflammatory response that occurs in the secondary injury phase of SCI. In this project, the focus was on determining whether GelMA hydrogels induce an inflammatory response in microglia, the resident immune cells of the central nervous system.

Sandwich ELISA and RT-qPCR were used to assess microglia polarisation (M1 and M2) markers. The hypothesis was that 3% GelMA hydrogels do not induce a significant inflammatory response in BV2 microglia over a 48 hour period. Statistical analysis included Shapiro-Wilk Normality Test, ordinary One-Way ANOVA, Dunnett’s Multiple Comparisons Test and Kruskal-Wallis test.

The results corroborated the original hypothesis; 3% GelMA hydrogels do not cause a significant change in the secretion of TNF-α & IL-10 from BV2 microglia at 24hr and 48hr. Furthermore, 3% GelMA does not cause a significant change in the expression of M1 markers (TNF-α and iNOS) nor M2 markers (Arg-1 and CD206) at 24hr and 48hr.

These findings suggest that GelMA hydrogels provide an effective platform for sustained drug delivery in a model of SCI. Future work aims to determine additional CNS cell responses to 3% GelMA hydrogels (e.g. neurons, astrocytes, and oligodendrocytes) as well as its effectiveness in an in vivo rodent model of SCI.

References

Dooley D, Lemmens E, Vangansewinkel T, Le Blon D, Hoornaert C, Ponsaerts P, et al. Cell-Based Delivery of Interleukin-13 Directs Alternative Activation of Macrophages Resulting in Improved Functional Outcome after Spinal Cord Injury. Stem Cell Reports. 2016;7(6):1099-1115.

Walsh C, Wychowaniec J, Brougham D, Dooley D. Functional hydrogels as therapeutic tools for spinal cord injury: New perspectives on immunopharmacological interventions. Pharmacology & Therapeutics. 2022;234:108043.

Presenting Author: Louise Costello

Supervisor: Dr Dearbhaile Dooley

FEARFULNESS RESPONSES OF THOROUGHBRED BROODMARES TO A NOVEL OBJECT

Rand A 1 , Moss A 1 , O’Reilly O 1 , Katz L 1

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

The post-natal environment is dependent on maternal care style (MCS). MCS has been assessed in Arabians using fearfulness responses [1]. The aim was to test the hypothesis that fearfulness responses could be established in Thoroughbred (Tb) broodmares. The objective was to assess correlations between subjective behavioural scores and objective measurements of fearfulness.

Broodmares ( n =25, 5-16 years old) were recruited from one farm: n =17 multiparous, n =8 ≤1 prior foal. Mares were instrumented with an ECG heart rate (HR) monitor and a 5-minute recording taken of the response to an umbrella opening. Two observers reviewed the videos, with measurements averaged and intra-assay coefficient of variations (CV) calculated (Table 1). Pearson’s correlation was used to assess associations between subjective and objective scores, age and parity ( r ≥0.4 correlation). Data is presented as mean ± standard deviation.

The mean startle response to the umbrella opening was 12.1±9.8 sec, with horses reaching a mean peak and average HR of 110.0±34.3 and 65.5±21.8 bpm, respectively. Mean separation and behavioural scores were 3.4±0.9 and 3.2±0.8, respectively. The startle response was moderately correlated to age ( r =0.54), parity ( r =0.65) and mean HR ( r =0.42). Behavioural scores were moderately correlated to age ( r =-0.53), parity ( r =-0.55), startle response ( r =-0.55), duration of touching object ( r =0.61), peak HR ( r =-0.58) and average HR ( r =-0.60).

The results demonstrate correlations between objective and subjective scores of fearfulness to a novel object. Correlations between age, parity, the startle response, HR and behavioural scores may indicate increased experience with environmental stimuli. Associations of fearfulness with MCS need to be explored.

Reference

Budzynska M, Krupa W. Relation between fearfulness level and maternal behaviour in Arab mares. Animal Science Papers and Reports. 2011;29:119-29.

Presenting Author: Amy Rand

Supervisor:Prof Lisa Katz

EXAMINING THE PRESENCE OF OXIDATIVE STRESS IN INDIVIDUALS WITH POLYCYSTIC OVARIAN SYNDROME: A META-ANALYSIS

Terenzi DC 1,2 , Bakbak E 2,3 , Hess DA 3,4,5 and Verma S 2,3,6,7

1 UCD School of Medicine, University College Dublin, Ireland

2 Division of Cardiovascular Surgery, St. Michael's Hospital, Toronto, ON, Canada

3 Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada

4 Molecular Medicine Research Laboratories, Krembil Centre for Stem Cells Biology, Robarts Research Institute, University of Western Ontario, London, ON, Canada

5 Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada

6 Department of Surgery, University of Toronto, Stewart Building, Toronto, ON, Canada

7 Institute of Medical Science, University of Toronto, Toronto, ON, Canada

Polycystic Ovarian Syndrome (PCOS) remains a challenging endocrine disorder, affecting up to 1 in 5 women of child-bearing age (1). Characterized by hyperandrogenism, oligomenorrhea and the presence of ovarian cysts, this syndrome is associated with multiple disease manifestations including infertility, type 2 diabetes and cardiovascular disease (CVD) (1).

The role of PCOS to the progression and manifestation of CVD remains unknown. Recently, the contribution of oxidative stress has gained attention as a major player in disease pathology, including CVD (2) due to its influence on DNA damage and cellular dysfunction (2). In this meta-analysis, the role of markers of oxidative stress known to contribute to the development of CVD are examined in individuals with PCOS compared to those without PCOS.

Following data accrual and extraction of 16 articles from PubMed and Google Scholar, the examination of markers such as glutathione and superoxide dismutase revealed that the antioxidant capacity of individuals with PCOS is significantly decreased compared to individuals without PCOS. Furthermore, pro-oxidant markers such as malondialdehyde were significantly elevated in individuals with PCOS compared to those without PCOS.

Therefore, current literature suggests a possible connection between the disproportional balance of oxidative stress in individuals with PCOS, consistent with observations in CVD. Consequently, the increased oxidative stress demonstrated in PCOS may play a role in the progression of CVD through atherosclerotic plaque development and dysfunctional cardiomyocyte contraction (2). Future studies should investigate the affected cellular microenvironment to better understand the role of oxidative stress and PCOS in the development of CVD.

References

Teede H, Deeks A, Moran LJ. Polycystic ovary syndrome: A complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC Med [Internet]. 2010;8(41):1–10.

Fenkci V, Fenkci S, Yilmazer M, Serteser M. Decreased total antioxidant status and increased oxidative stress in women with polycystic ovary syndrome may contribute to the risk of cardiovascular disease. Fertil Steril. 2003;80(1):123–7.

Presenting Author: Danielle Terenzi

Supervisor: Prof Subodh Verma

MOLECULAR DYNAMICS SIMULATIONS OF SARS-COV-19 OMICRON VARIANT PEPTIDES WITH MAJOR HISTOCOMPATIBILITY COMPLEXES

Vander Heyden K 1 , Riedel M 2 , Vasmatzis G 3 , Cornette J 4 , Udell J 2, 3 , Solanki A 2, 3

1 UCD School of Medicine, University College Dublin, Ireland

2 University of Minnesota, Minneapolis, MN 55455, USA

3 Center for Individualized Medicine, Biomarker Discovery Group, Mayo Clinic, Rochester, MN, USA

4 Iowa State University, Ames, IA, USA

Predictions of the binding strength of the immune system to viral peptides via major histocompatibility complexes (MHCs) is currently best done via neural networks 1 . This project sought to make these predictions from chemical interactions via molecular dynamics simulations.

The SWISS-MODEL software was utilised to obtain the Protein Data Bank (PDB) entry name for the desired MHC molecule. Alternatively, SWISS-MODEL found the most homologous crystallised MHC if the desired MHC’s structure was not crystallised. The CHARMM-GUI interface performed any required mutations to the entry’s amino acid sequence such that the file matched the target MHC sequence. Different peptide conformations were obtained by extracting bound peptides in PDB entries and mutating them to match the target viral peptide while retaining the original conformation. CHARMM software was later used to iteratively minimise the energy of the MHC-peptide complex to obtain a stable energy conformation 2 .

Once simulations were completed, the energy of how the peptide and MHC molecule interacted on a chemical level was recorded. The results of our simulations showed that molecular dynamics simulations can achieve both peptide conformations and interaction energy values representative of known structures. This suggests that viral peptide binding strength predictions relying on chemical interactions rather than neural networks are feasible.

This ongoing project will continue to develop and refine simulation techniques to ultimately predict the binding strength of novel virus peptides. Accurately making these predictions for a novel virus would enable the creation of a statistical model to predict a patient’s disease severity based on their MHC alleles.

References

Lundegaard C, Lamberth K, Harndahl M, Buus S, Lund O, Nielsen M. NetMHC-3.0: accurate web accessible predictions of human, mouse and monkey MHC class I affinities for peptides of length 8-11. Nucleic Acids Research. 2008; 36(2):W509-W512.

Brooks BR, Brooks III CL, Mackerel AD, Nilsson L, Petrella RJ, Roux B, et al. CHARMM: the biomolecular simulation program. J Comput Chem. 2009; 30:1545-1615.

Presenting Author: Kevin Vander Heyden

Supervisor: Prof Marc Riedel

THE ASSOCIATION BETWEEN SOCIAL DETERMINANTS OF HEALTH AND VISION REHABILITATION OUTCOMES

Achanta P 3 , Rizzo JR 1 , Beheshti M 2

1 NYU Langone Health, New York, New York, USA

2 Rusk Rehabilitation Center, New York, New York, USA

3 UCD School of Medicine, University College Dublin, Ireland

Social determinants of health (SDOH) are the non-medical factors, forces, and systems that shape conditions of daily life and influence health outcomes. SDOH have direct and indirect effects on lifestyle, health behaviors, and are linked to chronic diseases, such as diabetes and cardiovascular disease [1]. Research has classically focused on the association between SDOH and the acquisition of disease rather than the progression and outcomes of disease [2]. Furthermore, there is a large gap in scientific literature with respect to the relationship between SDOH and rehabilitation outcomes. In the present study, we consider SDOH and their associations with vision rehabilitation outcomes through literature review. Once granted access to data, our primary SDOH of consideration will include socioeconomic status (SES), ethnicity, access to health care, built environment including the quality of housing and vision-friendly environments, and access to transportation, all of which may modify rehabilitation outcomes for patients with visual impairments (VI). Vision rehabilitation outcomes of consideration include high level factors such as attendance, sustained adherence, and self-reported patient health status/ quality of life (QoL). In the future, we hope to extrapolate these findings to functional outcome measures of vision rehabilitation including improvements in oculomotor performance during eye hand coordination assessments. The present study is significant as having a better understanding of SDOH and their impacts on vision rehabilitation is crucial to informing rehabilitation services so they can best serve patients with VI.

References

Datto, A., n.d. Social determinants of health. [online] Who.int.

Bonnell, L., Crocker, A., Kemp, K., & Littenberg, B. (2021). The Relationship Between Social Determinants of Health and Functional Capacity in Adult Primary Care Patients With Multiple Chronic Conditions. The Journal Of The American Board Of Family Medicine, 34(4), 688-697

Presenting Author: Priya Achanta

Supervisor: Assoc Prof John-Ross Rizzo

IN SITU HYBRIDIZATION FOR DETECTING BACTERIAL GENE EXPRESSION IN EARLY-STAGE BREAST CANCER

Yacoob J 1 , Burke C 2 , Gallagher WM 2 , Rahman A 1,2

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

2 Cancer Biology and Therapeutics (CBT) Laboratory, UCD Conway Institute of Biomedical and Biomolecular Research, University College Dublin, Ireland.

10-30% of those with early-stage, lymph node-negative breast cancer develop a recurrence following surgical resection [1] resulting in patients undergoing unnecessary treatment. Dysbiosis can be a contributing factor to the development of cancer. Pathogenic bacterial species, such as Fusobacterium nucleatum, have been proven to accelerate tumor growth and metastatic progression by promoting tumorigenesis. The aim of this study was to explore and validate the Hybridization Chain Reaction RNA-FISH (HCR RNA-FISH) assay [2] to investigate the expression of Escherichia coli (E. coli) in a quantitative and spatial context within the breast tumor microenvironment.

RNA-FISH detects the presence of specific transcripts by using nucleic acid probes linked to reporter molecules such as fluorophores. In this experiment, we attempted to validate the HCR RNA-FISH assay [2] using probes designed to target 16S E. coli rRNA. The results generated by the protocol were then compared to an already established protocol (RNAScope-Multiplex -Fluorescent-V2-assay) to assess its utility.

A high amount of background signal was associated with the protocol, in addition to unspecific staining in our negative mammalian cell line. Various experimental conditions were tested (incubation time, hybridization time etc.), however, the background signal did not improve. Our results indicated that this method requires fundamental improvement prior to widespread use in biomarker validation.

Therefore, it would be recommended to adopt the use of the RNAScopeV2 assay over the HCR RNA-FISH assay. The RNAScopeV2 assay has already been validated by the lab, and it holds great potential for future use in exploring prognostic biomarkers in breast cancer.

References

Lanigan F, Brien GL, Fan Y, Madden SF, Jerman E, Maratha A, et al. Delineating transcriptional networks of prognostic gene signatures refines treatment recommendations for lymph node-negative breast cancer patients. FEBS J. 2015 Sep;282(18):3455-73.

Schwarzkopf M., Liu M., Schulte S., Ives R., Husain N., Choi H., and Pierce N., 2021. Hybridization chain reaction enables a unified approach to multiplexed, quantitative, high-resolution immunohistochemistry and in situ hybridization. Development , 148(22).

Presenting Author: Javed Yacoob

Supervisor: Dr Arman Rahman

Co-Supervisor: Prof William Gallagher

INVESTIGATION OF ANTIMICROBIAL RESISTANCE IN A SEAL REHABILITATION FACILITY

Hung J 1 , Vale AP 1

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

Gram negative bacteria found in the faecal microbiota of marine mammals are known to have both acquired and intrinsic resistance to many antimicrobials. Recently, acquired resistance to antimicrobials was identified in E. coli isolated from Irish grey seals ( Halichoerus grypus ) and harbour seals ( Phoca vitulina ) (Vale et al., 2021). With the rise of multidrug resistant Gram negative bacteria, treatment of infections is becoming more difficult jeopardizing animal and human health. This project aimed to characterize the antimicrobial resistance (AMR) profile of E. coli and other Gram negative bacteria isolated from seals’ faeces, water, fish soup and the environment at a seal rehabilitation facility.

Sampling was conducted on June 27, 2022 at Seal Rescue Ireland. Environmental samples were taken from 5 individual pens in use at the time, and 3 washed wet suits (surrogate mothers) using tissue swabs. Additionally, samples were taken from tap water, river water, 2 fish soups (26/06/22 and 27/06/22) and faeces from 2 seals. Water samples were processed through a membrane filtration unit with a 0.45µm pore size and membrane filters were either placed into Buffer Peptone Water (BPW) and incubated for 24 hours at 35ºC for total DNA extraction (Dallenne et al., 2010) or placed onto selective chromogenic media and incubated for 22 hours at 37ºC. Additionally, a 97 well Colilert system was used to detect and quantify both total coliforms and E. coli in water samples. Environmental swabs and fish soups were suspended in 90mL of BPW. Homogenized samples were then plated onto selective and chromogenic media: Tryptone Bile X-Glucoronice (TBX) (selective for E. coli ), CHROMID ® Colistin R Agar (selective for colistin resistant Enterobacteriaceae) and CHROMID ® ESBL (selective for Extended-Spectrum Beta Lactamase-producing Enterobacterales ) plates and incubated for 22 hours at 37ºC (bioMérieux Clinical Diagnostics, 2022).

Coliforms and E. coli were only detected in the river water sample with a most probably number (MPN) of 1986.3 for both. Twelve Gram negative isolates were recovered from CHROMID ® ESBL plates and 15 Gram negative isolates including E. coli were isolated from CHROMID® Colistin R plates from environmental samples and seal faeces. Overall, 48 isolates were recovered.

Characterization of AMR in E. coli and other Gram negative bacteria within this population is important because seals are sentinel species that often reflect water quality/environmental contamination. The phenotype of isolates recovered from CHROMID® Colistin R and CHROMID® ESBL plates is of public health concern thus further investigation is ongoing.

References

bioMérieux Clinical Diagnostics. 2022. bioMérieux Clinical Diagnostics . [online] Available at: https://www.biomerieux-diagnostics.com [Accessed 5 August 2022].

Dallenne, C., Da Costa, A., Decré, D., Favier, C. and Arlet, G., 2010. Development of a set of multiplex PCR assays for the detection of genes encoding important β-lactamases in Enterobacteriaceae. Journal of Antimicrobial Chemotherapy, 65(3), pp.490-495.

Vale, A., Shubin, L., Cummins, J., Leonard, F. and Barry, G., 2021. Detection of blaOXA-1, blaTEM-1, and Virulence Factors in E. coli Isolated From Seals. Frontiers in Veterinary Science , 8.

Vale, A., Shubin, L., Cummins, J., Leonard, F. and Barry, G., 2021. Detection of blaOXA-1, blaTEM-1, and Virulence Factors in E. coli Isolated From Seals. Frontiers in Veterinary Science , 8.

Presenting Author: Jennifer Hung

Supervisor:Dr Ana Vale

THE PREVALENCE AND SEVERITY OF BURNOUT AMONG MEDICAL STUDENTS AT UNIVERSITY COLLEGE DUBLIN

Ahmad M 1 , Donohue G 1 , O’Donnell B 1

1 UCD School of Medicine, University College Dublin, Ireland

Academic burnout is an undesirable outcome that could arise from stressful university workload, which may cause emotional or social fatigue. 1 This study utilised the Maslach Burnout Inventory-Student Questionnaire (MBI-GS-S) to gauge the extent and the severity of overall burnout and on three subscales – emotional exhaustion (EE), cynicism (CY), and academic efficacy (AE) – among the preclinical medical students at University College Dublin (UCD).

This cross-sectional study utilised online and anonymous MBI-GS-S. It is a sixteen-item scale with three subscales marked on a seven-point Likert scale. A Higher score of AE indicates lower burnout, and higher scores of EE and CY indicate higher burnout. The questionnaire was conducted in a sample of 97 students (14.9% of UCD preclinical medical students) from different stages. Furthermore, a cluster analysis was conducted to categorise the students into appropriate burnout profiles.

There were 38 (39.6%) male and 58 (60.4%) female students. However, the mean scores of EE, CY, and AE were 4.28 ± 1.30, 2.83 ± 1.58, and 3.64 ± 1.11 consecutively; (range: 0-6). Overall moderate to high burnout was found in 45.36% of the students, and 29.90% being at high risk for burnout. It is important to note that the prevalence of burnout was 2-fold higher in international students compared to Irish students. However, gender was not significantly associated with any of the subscales of burnout.

This highly prevalent burnout level could possibly lead to a detrimental impact on the quality of life and the learning experience. 2 Therefore, evaluating interventions to improve wellbeing is essential.

References

Galán F, Sanmartín A, Polo J, Giner L. Burnout risk in medical students in Spain using the Maslach Burnout Inventory-Student Survey. Int Arch Occup Environ Health [Internet]. 2011 Mar 04 [cited 2022 August 04];84(4): 453 – 459. Available from: https://pubmed.ncbi.nlm.nih.gov/21373879/

O’Dea B, O’Connor P, Lydon S, Murphy A. Prevalence of burnout among Irish general practitioners: a cross-sectional study. Ir J Med Sci [Internet]. 2016 Jan [cited 2022 August 04];186(2): 447 – 453. Available from: https://pubmed.ncbi.nlm.nih.gov/26803315/

Presenting Author: Mohannad Ahmad

Supervisor: Dr Barry O’Donnell

Co-Supervisor: Dr Gráinne Donohue

HANG UP YOUR CLEATS AND HOPE FOR THE BEST? A CROSS-SECTIONAL STUDY INVESTIGATING RETIRED ELITE FEMALE RUGBY PLAYERS’ HEALTH

Harrison C 1 , Thornton J 2

1 UCD School of Medicine, University College Dublin, Ireland

2 Fowler Kennedy Sports Medicine Clinic, University of Western Ontario, London, Ontario, Canada

This study investigated the long-term health outcomes of elite, retired female rugby players. Minimal research has been conducted within the fields of sports medicine and acute/chronic injury prevention on this subject. Specifically, there is a disproportional lack of evidence on the lifelong physiological and psychological associations that contact-sport participation has on high-performance female athletes compared to their male counterparts [1].

Three consenting participants’ musculoskeletal, neurocognitive, reproductive/endocrine, mental and cardiovascular health were assessed to address this critical knowledge gap. A mixed-methods, cross-sectional design was implemented as participants completed an anonymized online self-reported questionnaire and a cognitive computer test. Various gold-standard academic survey questions were incorporated within the questionnaire, while the cognitive test assessed twelve essential neurocognitive domains.

Participants’ data provided a unique perspective on the long-term effects conferred by competitive sport. Their responses highlighted chronic musculoskeletal injuries, sports-related concussions (SRCs), anxious/depressive symptoms, and disordered eating habits. Unlike previous literature that has demonstrated the long-term neurocognitive ramifications of head collisions via contact-sport participation [2], no detrimental findings were indicated within each participant’s neurocognitive functioning. A major limitation was the study’s small sample size, not allowing for significant statistical analysis.

This preliminary study endeavoured to provide instrumental knowledge on the long-term impact that participation in international-calibre rugby has on retired female athletes. A larger-scaled longitudinal cohort study is essential to examine further the complex interrelations of contact-sport and the female athletic body. This will allow for the successful promotion and advancement of future safety guidelines/protocols, protecting current and future female athletes’ lifelong health.

References

Cowley ES, Olenick AA, McNulty KL, Ross EZ. “invisible sportswomen”: The sex data gap in sport and exercise science research. Women in Sport and Physical Activity Journal. 2021;29(2):146–51.

Cunningham J, Broglio SP, O'Grady M, Wilson F. History of sport-related concussion and long-term clinical cognitive health outcomes in retired athletes: A systematic review. Journal of Athletic Training. 2020;55(2):132–58.

Presenting Author: Chase David Harrison

Supervisor: Dr Jane Thornton

DEVELOPMENT OF A BENCHTOP TEMPERATURE CONTROL SYSTEM FOR MICROGLIAL LIVE-CELL IMAGING IN VITRO

Alroqi M 1 , O’Carroll R 1 , Reynolds JP 1 Dooley D 1,2

1 UCD School of Medicine, University College Dublin, Ireland

2 UCD Conway Institute of Biomolecular & Biomedical Research, UCD School of Medicine, University College Dublin, Ireland

Traumatic Spinal Cord Injury (SCI) is a significant medical problem worldwide, which diminishes quality of life and leads to severe functional impairments. SCI is characterised by the loss of motor, sensory and autonomic function below the lesion level that results from damage to and death of local neurons and glia. An initial primary injury phase exists, which is followed by a secondary, chronic neuroinflammatory phase, consisting of inflammatory cytokine release, axonal dieback and astroglial scar formation. 1,2 Scratch wound assay (SWA) is a simple in vitro model of scar formation observed in SCI. However, current analysis methods are limited, with ‘before/after’ snapshots of cell density commonly used as a surrogate for migration.

Here we present a prototype live-cell optical imaging system, which captures cellular motion in real time over extended imaging trials. Briefly, BV2 microglia were maintained between 32-37 °C on the benchtop using a custom temperature control system and peristaltic pump to continuously circulate medium. pH, osmolality & flow rate were controlled for the duration of each experiment. Time lapse images were captured using a brightfield microscope.

In our optimized system, microglia did not display features of necrosis or apoptosis, i.e., no membrane blebbing, nuclear fragmentation or lysis, and remained viable and motile. Overall, this is a novel method for live-cell imaging on the lab bench, which allows longitudinal analysis at physiological conditions.

Further optimisation of this imaging system will be required, and additional data analysis techniques such as motion tracking and morphology analysis will be employed for a more comprehensive quantification of cell behaviour.

References

Rust, R. and Kaiser, J. (2017) Insights into the Dual Role of Inflammation after Spinal Cord Injury. The Journal of Neuroscience , 37(18), pp.4658-4660.

Dooley, D. et al . (2016) Cell-Based Delivery of Interleukin-13 Directs Alternative Activation of Macrophages Resulting in Improved Functional Outcome after Spinal Cord Injury. Stem Cell Reports , 7(6), pp.1099-1115.

Presenting Author:Mazen Alroqi

Supervisor:Dr Dearbhaile Dooley

CHARACTERISATION OF EXOSOMES FROM PATIENTS WITH LYMPHANGIOLEIOMYOMATOSIS (LAM) AND TSC- /- MUTATED CELL LINES

Buckley G 1 , McCarthy C 2 , Jouida A 2

1 UCD School of Medicine, University College Dublin, Ireland

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

Exosomes are extracellular vesicles between ~30 and 200nm in diameter1. Lymphangioleiomyomatosis (LAM) is a rare cystic lung disease characterised by abnormal growth of smooth muscle cells, lungs, lymphatic system and kidneys. Western blots using exosomes markers, CD63 and CD81, was done to confirm the presence of exosomes as well as to compare the expression of vimentin and E-cadherin in samples of A549 cells exposed to 50ug/ml of exosomes derived from either LAM or healthy samples. Nanoparticle analysis was carried out to determine the number of particulates per milliliter and zymography was preformed to measure the proteolytic activity of the matrix metalloproteinases, MMP-2, -9 and Pro-MMP-9.

The results found an increase in particulate number per milliliter in LAM samples (p=0.0273), a negative correlation between the particulates number per milliliter and forced expiratory volume 1% (p=0.0295, R=-0.4667, N=17), a positive correlation between particulates number per milliliter and VEGF level (pg/ml) (p=0.0496, R=0.4690, N=18), and an increase in particulates number per milliliter in patients without chylothorax (p=0.0185, N=3). There was an increase in proteolytic activity for Pro-MMP-9 in LAM samples (p=0.0278, N=18), and the A549 cells exposed to exosomes from LAM samples saw an increases in vimentin and E-cadherin expression, two markers of EMT2 (p=0.0108, P=0.0268). These results demonstrate the potential of exosomes as biomarker in LAM diagnosis. Further research could be done to determine the nature of EMT.

References

Z, N., A, M., A, E., Z, H. and R, S., 2022. Significance of E-cadherin and Vimentin as epithelial-mesenchymal transition markers in colorectal carcinoma prognosis. [online] PubMed.

Zhou, B., Xiang, J., Jin, M., Zheng, X., Li, G. and Yan, S., 2021. High vimentin expression with E-cadherin expression loss predicts a poor prognosis after resection of grade 1 and 2 pancreatic neuroendocrine tumors. BMC Cancer, 21(1).

Presenting Author: Grace Buckley

Supervisor: Assoc Prof Cormac McCarthy

MOVING TOWARDS SUSTAINABLE CLINICAL RESEARCH

Kalusche M 1 , Doran P 2 , Holden S 2

1 UCD School of Medicine, University College Dublin, Ireland

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

Clinical trials are vital in delivering high-quality, safe, and effective healthcare. However, the healthcare sector is responsible for 4.6% of global greenhouse gas emissions (GHG) 1 and clinical research is responsible for a considerable carbon footprint, due to patient/staff travel, as well as resources for patient and onsite energy usage 2 . There is a need to make clinical trials more sustainable. This study aims to quantify the carbon cost in clinical trials, to develop guidance for the design and running of clinical trials to minimise GHG.

This study is designed as a retrospective audit of trials conducted at the Clinical Research Centre (CRC). Data was collected from sources at the CRC, and included the trial protocol, trial master file and trial data. Carbon calculators were used to estimate the carbon associated with the trial elements; patient travel, trial team related travel, shipments of trial materials (including IMP), and energy usage onsite.

This study included five trials (only one was not randomised), with 111 participants and an average number of patient visits of 327. The trials resulted in an overall emission of 41.46 tonnes of CO 2 (range=23.47, IQR=14.38). The largest contributor was patient travel, 41.43%, and the smallest contributor was the energy usage from onsite, 10.8%.

This study shows a change to the previous studies and demonstrates the impact of the pandemic on the design and conduct of clinical trials. Action can be taken to reduce the carbon footprint of clinical trials, such as moving to remote patient/monitoring visits.

Acknowledgements

The Clinical Research Centre would like to acknowledge the HRB-TMRN for their funding of this research.

References

WHO. Countries commit to develop climate-smart health care at COP26 UN climate conference nternet]. World Health Organisation; 2021 [cited 2022 Jul 26]. Available from: https://www.who.int/news/item/09-11-2021-countries-commit-to-develop-climate-smart-health-care-at-cop26-un-climate-conference

Lyle K, Dent L, Bailey S, et al. Carbon cost of pragmatic randomised controlled trials: retrospective analysis of sample of trials. BMJ [Internet]. 2009 Oct 10 [cited 2022 Jul 26] 339:b4187. Available from: https://doi-org.ucd.idm.oclc.org/10.1136/bmj.b4187

Presenting Author: Maeve Kalusche

Supervisor: Dr Sinead Holden

THE EFFECT OF STERILE INTRA-AMNIOTIC INFLAMMATION ON NEONATAL LIFE

Glazier C 1 , Farias-Jofre M 2 , Gomez-Lopez N 2,3,4

1 UCD School of Medicine, University College Dublin, Ireland

2 Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS); Bethesda, Maryland and Detroit, Michigan, USA

3 Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan, USA

4 Department of Biochemistry, Microbiology and Immunology, Wayne State University School of Medicine, Detroit, MI, USA

Preterm birth remains a leading cause of neonatal morbidity and mortality worldwide. Preterm infants are at increased risk of both acute and long-term complications. The most well-established cause of spontaneous preterm birth is inflammation of the amniotic cavity, primarily sterile intra-amniotic inflammation (SIAI). The specific effects of SIAI on neonatal life have not previously been fully studied. Thus, our aim was to investigate the association between the perinatal outcomes of SIAI and the effects on neonatal life.

We used an animal model of SIAI previously established by our lab. 1 Female C57BL/6 mice were mated with male C57BL/6 mice. Pregnant dams received ultrasound-guided intra-amniotic injection of IL-1α or phosphate-buffered saline as control. Rate of preterm birth, mortality at birth, neonatal survival and growth were recorded. Neurobehavioral testing was performed at 5 days of postnatal life and consisted of surface righting, cliff aversion, and negative geotaxis. Data analysis was performed using the Mann-Whitney U-test.

IL-1α injection increased the rate of premature birth (p=0.019) and mortality at birth (p=0.029). Exposure to intra-amniotic IL-1α was associated with reduced neonatal survival at 3 weeks of postnatal life (p<0.001) and reduced growth, with diminished weight (p=0.014) and biparietal diameter (p<0.001). Neurobehavioral testing did not reveal significant differences for either surface righting or cliff aversion, however a greater proportion of pups failed negative geotaxis in litters of dams injected with IL-1α (p=0.024).

Our results show that SIAI affects neonatal life. Future research will be focused on interventions to prevent adverse perinatal and neonatal outcomes associated with SIAI.

Reference

Motomura K, Romero R, Garcia-Flores V, Leng Y, Xu Y, Galaz J, Slutsky R, Levenson D, Gomez-Lopez N. The alarmin interleukin-1α causes preterm birth through the NLRP3 inflammasome. Mol Hum Reprod. 2020 Sep 1;26(9):712-726.

Presenting Author: Catherine Glazier

Supervisor: Assoc Prof Nardhy Gomez-Lopez

ADENOSINE RECEPTOR SIGNALLING INCREASES MUCIN PRODUCTION IN THE INTESTINAL EPITHELIUM

Lee O 1 , Aljubury M 1, 2 , Stepanova M 1,2 , Aherne CM 1, 2

1 UCD School of Medicine, University College Dublin, Ireland

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

The mucus gel layer (MGL) lining the intestinal epithelium separates epithelial cells from luminal contents. Early MGL disruption is observed in inflammatory bowel disease (IBD) models and patients. Therefore, MGL dysfunction is thought to be important in IBD development. Strategies to improve MGL function are under investigation as novel IBD treatments. The mucin MUC2 is the major component of the MGL in the colon and ileum. The Aherne lab identified a novel protective role for the mucin MUC5AC in IBD. The lab also observed that the Adora2B adenosine receptor (A2BAR) protects the colon in murine IBD. Adenosine signaling has been demonstrated to increase mucin expression in lungs. Therefore, we hypothesised that adenosine signaling may increase mucin expression in the intestine.

T84 intestinal epithelial cells were treated with increasing concentrations of NECA, an A2 receptor agonist with varying specificity for A2B & A2A receptor (A2AAR). MUC2 and MUC5AC mRNA expression were measured using TaqMan RT-PCR. T84 cells were co-treated with NECA and A2AAR or A2BAR specific antagonist to determine the role of each receptor in mucin expression. Immunofluorescence with MUC5AC specific antibodies measured MUC5AC protein expression in A2BAR agonist-treated HT29-MTX-E12 cells.

NECA induces MUC2 and MUC5AC mRNA expression in a concentration dependent manner. NECA-induced MUC2 and MUC5AC mRNA expression was reduced to control levels with either the A2AAR or A2BAR antagonist suggesting NECA signals via both receptors to increase mucin expression. The A2BAR specific agonist induces MUC5AC protein expression.

Our findings suggest that A2AAR and A2BAR activation could promote MGL restitution.

Presenting Author: Lee Onn

Supervisor: Dr Carol Aherne

POST MORTEM FINDINGS IN GREY SEALS ( HALICHOERUS GRYPUS ) AND HARBOUR SEALS ( PHOCA VITULINA ) STRANDED ON THE IRISH COAST

Zhang H 1 , Saint-Marc A 1 , Imlau M 2 , Plamenova E 2 , Jahns H 2

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

2 Institute of Animal Health and Food Safety, Faculty of Veterinary Medicine, University of Las Palmas de Gran Canaria, Spain

Establishing the cause of death of marine mammals such as stranded seals can provide valuable information on the wildlife population, changes of the coastal marine environment, and the presence of zoonoses including influenza and other infectious diseases of veterinary importance.

Post-mortem examinations were conducted on 53 grey seals and 13 harbour seals stranded between November 2019 and February 2022 along the Irish coast to determine the cause of death, monitor parasite burden and establish a comprehensive tissue bank for future research. Detailed history, signalment, clinical signs, and pathological changes found on necropsy were recorded. Parasites were identified morphologically under the microscope. A wide range of tissue samples was fixed in 10% formalin and frozen.

Stranded seals were mostly neonates/juveniles, with a majority of them found during their respective pupping season. The most common causes of death were septicaemia often secondary to conspecific trauma, followed by emaciation and parasitic bronchopneumonia. Less frequently identified causes included: other types of trauma, peritonitis, endoparasitism including heartworm, myositis, aspiration pneumonia, pyothorax, pneumothorax and haemoabdomen. Overall, the respiratory and alimentary tracts were the organ systems most affected. The main parasites found were nasal mites ( Halarachne halichoeri) in 43.9% of seals, Anisakis nematodes in the stomach in 25.8% and lungworm ( Otostrongylus circumlitus) in 22.7%.

The above findings are similar to those reported in seals in the North Sea and North Atlantic. The large numbers of conspecific trauma and marked parasite burden may suggest intra and inter species encounters generated/reinforced by population density and/or local geographic conditions.

Acknowledgements

The authors would like to thank Brian Cloak, Michael Dixon and Amanda Lawlor for their technical support. Thanks to the Irish Seal Sanctuary for providing the data and seals for this project.

Presenting Authors: Han Zhang

Supervisor: Dr Hanne Jahns

EVALUATING THE EFFICACY OF THE COVID-19 BOOSTER VACCINE IN PRODUCING AN EFFECTIVE T-CELL RESPONSE

Barve A 1 , Cortázar J 2 , Mallon PWG 2 , Kenny G 2

1 UCD School of Medicine, University College Dublin, Ireland

2 UCD Centre for Experimental Pathogen Host Research (CEPHR), School of Medicine, University College Dublin, Ireland

T-cell immunity protects against COVID-19. However, the cellular response to the wild type (S) or Omicron spike (OS) peptides, induced by COVID-19 Booster vaccines, has not been fully elucidated.

Individuals recruited to the All-Ireland Infectious Diseases cohort study provided peripheral blood mononuclear cells (PBMCs) before and 14 days after administration of a booster dose of BNT162b2. The PBMCs were stimulated with SARS-CoV-2 pooled peptides (S and OS), and the T-cell (CD4+ and CD8+) activation-induced markers were determined using flow cytometry. Pre- and post-booster responses were compared using a paired, two-tailed t-test. Data presented are mean (sd) unless otherwise specified.

3 individuals (median age 60) were analyzed. In terms of the CD4+ responses, there was no appreciable CD137+Ox40+ response to either peptides in the pre- or post-booster samples (SCD137+Ox40+:0±0.174vs0±0.125; OSCD137+Ox40+:0±0.129vs0±0.007). The HLA-DR+CD38+ post-booster response increased with S (0 to 0.005±0.003) but not with OS (0±0.011vs0±0.071). A PD1+ response to S was present pre- and post-booster (1.063±2.211vs0.533±2.967) but not to OS (0±0.978vs0±1.453). In the CD8+ subsets, the HLA-DR+CD38+ response to S decreased post-booster (0.048±0.198vs0.013±0.056) but not to OS pre- or post-booster (0±0.063vs0±0.019). The CD137+CD69+ response to S increased post-booster (0 to 0.072±0.117) but not to OS post-booster (0±0.411vs0±0.086). Lastly, the PD1+ response to S increased post-booster (0 to 0.049±0.288) but not to OS post-booster (0±0.648vs0±0.112). None of the increased responses reached statistical significance (all p>0.05).

No significant increase in CD4 or CD8 S or OS response was seen in these individuals post COVID-19 booster in this study. Larger cohorts will be required to confirm this finding.

Reference

McMahan K, Yu J, Mercado N, Loos C, Tostanoski L, Chandrashekar A et al. Correlates of protection against SARS-CoV-2 in rhesus macaques. Nature. 2020;590(7847):630-634.

Presenting Author: Arnav Barve

Supervisor:Dr Grace Kenny

Co-Supervisor: Prof Patrick Mallon

IMMUNE RESPONSES OF HORSES TO CYATHOSTOMINS – SHEDDING LIGHT ON

INFLAMMATORY CONDITIONS OF THE GASTRO-INTESTINAL TRACT

Dunne S 1 , Mulcahy 2 , Walshe N 1 , Byrne O 1 , Nugent E 1

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

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

Cyathostomins are omnipresent among horses with over 40 species recognized as equine parasites.

Cyathostomin burden in horses exists predominantly as hypobiotic larvae within the mucosa of the large intestine. Sudden local and inflammatory responses, as well as gut microbiome dysbiosis known as acute larval cyathostominosis occur when hypobiotic larvae resume development and emerge into the gut lumen.

Cyathostomins pervasive effect on the immune system of horses remains unclear (1). The aim of this project is to shed insight on the immune response elicited by horses in response to these parasites and aid their management. Histopathological and immunohistochemically stained sections of intestine from horses with cyathostomins were examined to measure the contribution of different cell types and cytokines contributing to their response to infection. A multiplex cytokine ELISA assay measured secreted cytokines. Measurements obtained were correlated with data on burden levels and species of cyathostomin present in each horse.

Results demonstrated measurable levels of FGF-2, IP10 and TNF-a in the colonic and caecal mucosa of all horses. Consistently high levels of FGF-2 were present, not previously described. A tenfold increase of TNF-a in the clinical case was seen, with IL-1-b and GRO also measurable. A positive correlation between B-cells, T-cells, macrophages, and Fox P3 cells; IP-10 and FGF-2, and a putative association between fecal egg count (FEC) and Neutrophils, FEC and Fox-P3 was established. Concurrent molecular speciation of larvae illustrated only Cylicocyclus insigne present in the clinical case suggesting this species may elicit a more potent immune response, potentially TNF-a related and that re-emergence may be a species-specific event.

Reference

5. Steuer A, Stewart J, Barker V, Adams A, Nielsen M. Cytokine and goblet cell gene expression in equine cyathostomin infection and larvicidal anthelmintic therapy. Parasite Immunology. 2020;42(6).

Presenting Author: Stacey Dunne

Supervisor: Prof Grace Mulcahy

Co- Supervisor: Dr Nicola Walshe

MUSCLE ASYMMETRY AND LOW BACK PAIN

K. Clougher 1 , G. Cunniffe 2 , A. Pierce 3 , S. Morris 1,2, 3

1 UCD School of Medicine, University College Dublin, Ireland

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

3 Beacon Centre for Orthopaedics, Dublin, Ireland

Low back pain (LBP) is a leading cause of productivity loss, with 223.5 million cases in 2019 worldwide 1 . Current theories highlight the cyclical nature of pain, inflammation, and muscle remodelling 2 . The aim of this project was to investigate recent literature on LBP, isokinetic strength testing, and muscle quality; and to develop protocols for isokinetic testing in LBP patients.

A review of recent literature was conducted, using the terms “back pain and muscle asymmetry”, “isokinetic testing hip”, “isokinetic trunk strength”, and “hip abductor strength, hip adductor strength”. Biodex hip testing protocols were assessed from the literature and the Biodex-4 user manual. Proof-of-concept testing was completed on project team member on the Biodex-4 at the Beacon Hospital Sports Lab.

Trends in the literature included: the cyclical nature of pain and muscle remodelling; interest in fatty infiltration distribution and extent; utilizing technology; and the potential of isokinetic testing to better understand injuries. Best practices for Biodex use should, in addition to manufacturer’s protocols, stabilize the free leg and provide patients a practice or learning session.

Views on LBP have evolved to include the role of pain and inflammation in perpetuating dysfunction and reducing muscle quality: poor muscle quality may be caused by pain, rather than vice versa. Fatty infiltration and isokinetic strength are promising targets for research, and have potential to improve both our understanding of LBP pathology and patient treatment plans. A promising avenue for future research is to establish a link between asymmetry in strength, quality, pain stage, and patient outcomes.

References

Wang L, Ye H, Li Z, Lu C, Ye J, Liao M, et al. Epidemiological trends of low back pain at the global, regional, and national levels. European spine journal. 2022;31(4):953-62.

Hodges PW, Danneels L. Changes in Structure and Function of the Back Muscles in Low Back Pain: Different Time Points, Observations, and Mechanisms. The journal of orthopaedic and sports physical therapy. 2019;49(6):464-76.

Presenting Author:Katherine Clougher

Supervisor:Prof Seamus Morris

Co-Supervisors:Dr Gráinne Cunniffe & Anthony Pierce

INVESTIGATION OF FACTORS POTENTIALLY RELATED TO DEVELOPMENT OF MODERATE AND SEVERE DYSPHAGIA FOLLOWING ANTERIOR CERVICAL DISCECTOMY AND FUSION (ACDF) SPINE SURGERY

Curran J 1,2 , McDonnell J 2 , Cunniffe G 2 , Duggan S 3 , Gillivan-Murphy P 3 , Darwish S 2 , Butler J 1,2

1 UCD School of Medicine, University College Dublin, Belfield, Dublin 4

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

3 Speech & Language Therapy Department, Mater Misericordiae University Hospital, Dublin, Ireland

Anterior cervical discectomy and fusion (ACDF) spine surgery is a procedure used to treat cervical pathologies including traumatic, degenerative, and congenital disorders. Dysphagia, or difficulty swallowing, is a regular complication after ACDF [1]. The purpose of this research was to retrospectively investigate risk factors potentially related to moderate and severe dysphagia following ACDF surgery in the National Spinal Injuries Unit.

Patients who underwent ACDF surgery and were subsequently referred to Speech and Language Therapy (SLT) for evaluation due to dysphagia arising from their surgical operation were investigated in this study. A list of these patients, between 2015 and 2022, was gathered and used to build a study database. Patient demographics (example: age, gender), characteristics (example: comorbidities) and surgical notes (example: mean vertebral levels fused) were collated. Statistical methods were employed to identify if any risk or surgical factors played a contributory role for those experiencing dysphagia. Statistical analysis included independent t-test and Fisher’s exact test with p<0.05 noted as statistically significant.

Patients (n=53) were identified and classified as having either mild (n=7), moderate (n=31) or severe (n=15) dysphagia respectively. Post-operative tracheostomy was noted to be correlated with severe dysphagia incidence (p-value: 0.03), which agrees with existing literature [2].

Results also indicate a relationship between alcohol consumption and dysphagia, however, prospective studies with a larger sample size would be required to verify this association. Additional studies should also focus on recording full datasets to comprehensively test correlations between parameters. Severe dysphagia remains a rare but important complication to investigate and consider.

References

Liu, J., Hai, Y., Kang, N. Chen, X., Zhang, Y . Risk factors and preventative measures of early and persistent dysphagia after anterior cervical spine surgery: a systematic review. Eur Spine J. 2018 Oct 7; 27:1209–1218

Skoretz SA, Anger N, Wellman L, Takai O, Empey A. A Systematic Review of Tracheostomy Modifications and Swallowing in Adults. Dysphagia. 2020 May 6; 35:935-947

Presenting Author: Jack Curran

Supervisor: Dr Gráinne Cunniffe

Co-Supervisor: Prof Joseph Butler

REDOX STRESS HANDLING IN NORMAL MELANOCYTES AND MELANOMA CELLS

Molloy G 1 , Casalou C 2 , Tobin D 2

1 UCD School of Medicine, University College Dublin, Ireland

2 UCD Charles Institute of Dermatology, University College Dublin, Dublin, Ireland

The term “melanoma” describes a heterogeneous group of melanocyte-derived cancers. Although less common than keratinocyte-derived skin cancers, melanoma is more aggressive and treatment-resistant, and is thus a leading cause of cancer-related deaths worldwide. While the link between ultraviolet (UV) radiation and skin cancers is well established, oxidative stress is also thought to be a key driver of melanocyte transformation and melanoma progression. During melanin synthesis, a high number of reactive oxygen species (ROS) are generated, leaving melanocytes particularly vulnerable to this stressor. While brown/black eumelanin exhibits ROS-scavenging activity to counteract this redox imbalance, red/yellow pheomelanin lacks the same antioxidant capacity, leaving melanocytes in a highly pro-oxidative state [1].

The aim of this project was to compare the response to oxidative stressors – such as H2O2 and UV radiation – (a) in healthy melanocytes -vs- melanoma cells, and (b) among melanoma cell lines exhibiting differences in melanin content and subtype. High-mobility group box 1 (HMGB1) expression was used to measure oxidative stress. HMGB1 is a widely expressed protein which exerts different functions depending on its location within a cell. HMGB1 exists primarily inside the nucleus, where it acts as a DNA chaperone. Upon cell damage – e.g. oxidative stress – HMGB1 is released into the cytoplasm, then passively secreted into the circulation, where it acts as a damage-associated molecular pattern (DAMP) [2].

The results of this project showed poorer redox stress handling in pheomelanin-rich melanoma cells, compared with eumelanin-rich melanoma cells. Furthermore, an increase in serum HMGB1 with disease progression in melanoma patients was observed.

Acknowledgments

The author would like to thank Prof. Desmond Tobin, Dr. Cristina Casalou, and Jay Mayatra at the Charles Institute of Dermatology for their guidance and contributions to this project. The author would also like to thank Dr. Shirley Potter and Dr. Stephanie Bollard at the Mater Misericordiae University Hospital for the contribution of patient samples.

References

Denat L, Kadekaro A, Marrot L, Leachman S, Abdel-Malek Z. Melanocytes as Instigators and Victims of Oxidative Stress. Journal of Investigative Dermatology. 2014;134(6):1512-1518.

Yu Y, Tang D, Kang R. Oxidative stress-mediated HMGB1 biology. Frontiers in Physiology. 2015;6.

Presenting Author:Grace Molloy

Supervisor:Dr Cristina Casalou

Co-Supervisor:Prof Desmond Tobin

A SYSTEMATIC REVIEW OF THE CLASSIFICATION OF GASTROINTESTINAL TRACT NEUROENDOCRINE NEOPLASMS IN STUDIES THAT UTILISE THE SURVEILLANCE, EPIDEMIOLOGY, AND END RESULTS PROGRAM AND THE NATIONAL CANCER DATABASE

Hanson T 1 , Hua M 2 , Yaeger L 2 , Rodriguez JZ 2 , Hammill C 2 .

1 UCD School of Medicine, University College Dublin, Ireland

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

Neuroendocrine neoplasms (NENs) are a rare, heterogeneous group of malignancies which affect neuroendocrine cells. Until recently, the system used to classify NENs varied across anatomical region and evolved constantly, causing confusion amongst researchers and clinicians. To resolve this, in 2018, the World Health Organisation developed a more consistent and uniform framework for classifying NENs. However, both the earlier and updated frameworks do not align well with how these tumours are categorised in national cancer registries such as the National Cancer Database (NCDB) and the Surveillance, Epidemiology, and End Results (SEER) Program. Based on this, it is possible that studies utilising these databases to research NENs have significant flaws in them.

This systematic review aims to determine whether the classification of neuroendocrine neoplasms of the gastrointestinal tract is applied correctly in scientific literature that utilise the NCDB and SEER.

A medical librarian performed a search of the Embase, Ovid, Scopus, CENTRAL, CDSR and Clinicaltrials.gov databases using the concepts of ‘neuroendocrine neoplasms’, ‘Surveillance Epidemiology End Results’, and ‘The National Cancer Database’. 1639 results were returned. 560 duplicates were removed. A researcher-performed screen of the remaining studies removed a further 819 studies and 42 duplicates.

Preliminary analysis found that in some studies, over 50% of NEN patients are included for analysis in the incorrect tumour designation.

Misuse of NEN nomenclature is significant as it has the potential to influence practitioners’ clinical decisions and affect patient outcomes. Further study is required to determine the extent of misclassification in the literature.

Presenting Author: Theodore Hanson

Supervisor: Dr Jacaranda Van Rheenen

MISSED OPPORTUNITIES IN THE DIAGNOSIS OF TUBERCULOSIS MENINGITIS

Simmons N 1,2 , Olsen MA 2 , Reale J 2 , Bailey 2 , Mejia-Chew C 2

1 UCD School of Medicine, University College Dublin, Ireland

2 Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine in St. Louis, Missouri, USA

Tuberculosis (TB) meningitis continuously has high morbidity and mortality. Early recognition and treatment is pivotal to improve prognosis. Declining TB incidence in the US has resulted in decreased clinical awareness, increasing potential risk of diagnostic delays. The objective was to determine the impact a missed opportunity (MO) for diagnosing TB meningitis has on 90-day mortality and cost of healthcare utilization. Secondarily, identify factors associated with a MO and predictors of 90-day mortality.

A Retrospective cohort of adult patients with central nervous system TB were identified in the Healthcare Cost and Utilization Project, State Inpatient and State Emergency Department Databases from eight states, using ICD-9 diagnosis code 013.X. MO was defined as signs, symptoms, and/or procedures suggestive of TB meningitis 6 months prior to the diagnosis. Univariate analysis of demographics, comorbidities, admission characteristics, and mortality compared between-group differences.

Of 893 patients with TB meningitis, 61.3% were male, 20.3% were white, 13.1% died within 90-days of diagnosis, and 44.0% had a MO. Comparing those with and without a MO, 90-day mortality (12.0% vs 14.0%; p=0.37) and mean cost of healthcare utilization ($83,416 vs $78,625; p=0.54) did not differ. 90-day mortality was higher with older mean age (60.1 vs 49.5; p=<.001), sepsis (41.9% vs 12.8%; p<0.001), and receiving mechanical ventilation (50.4% vs 12.4%; p<0.001) during the index admission.

Increased 90-day mortality was associated with older age, sepsis, and mechanical ventilation during the index admission for TB meningitis. Having a MO had no impact on mortality.

Acknowledgements

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

Presenting Author: Niamh Simmons

Supervisor:Dr Carlos Mejia-Chew

BARRIERS TO PELVIC EXAMS: WHAT STANDS IN THE WAY OF EMERGENCY MEDICINE PHYSICIANS?

Lennon Malbasha L 1 , Lostchuck E 2,3 , Scheuermeyer F 2,3 , Barbic D 2,3

1 UCD School of Medicine, University College Dublin, Ireland

2 Department of Emergency Medicine, Faculty of Medicine, The University of British Columbia, Vancouver, BC, Canada

3 Providence Health Care, Vancouver, British Colombia, Canada

People assigned female at birth (AFAB) presenting to the emergency department (ED) with possible gynaecological complaints such as pelvic pain and abnormal premenopausal bleeding should receive a pelvic exam as part of standard care. 1 Although it is considered a critical exam, ED physicians do not consistently perform pelvic exams on patients presenting with relevant signs and symptoms. 2 The present study includes a scoping literature review and the development of a survey aimed at understanding the barriers to conducting pelvic exams experienced by ED physicians.

The five-stage scoping review framework developed by Arksey, and O’Malley was followed 2 . An advanced literature search was carried out on EMBASE and PubMed using the key words ‘barriers to pelvic exam’ and ‘barriers to gynaecological exam’. Citation searching was also utilised.

Twelve studies were selected for review. The studies were broadly subdivided into barriers in general practice/primary care, the emergency department, and special populations. Barriers were separated into patient, physician and system barriers. Key barriers identified include physician gender, patient unwillingness, time pressure and equipment barriers. The results guided the development of a survey directed at emergency department physicians, with the aim of elucidating the barriers to conducting pelvic exams.

A pilot study for feasibility, survey clarity and readability, is currently in progress. The survey has been disseminated to Emergency Medicine physicians in British Columbia. Once survey responses have been returned, data analysis will begin. Phase two of the project will include a national study to explore larger trends around age, gender, and urban-rural trends.

References

Evans D, Goldstein S, Loewy A, Altman AD. No. 385-indications for pelvic examination. Journal of Obstetrics and Gynaecology Canada. 2019 Aug 1;41(8):1221-34.

Mohart AE, Banet GA, Katz ED. Resident Sex and the Pelvic Exam: The Effect of Physician Sex on Selection and Management of Patients Who May Require a Pelvic Exam. Annals of Emergency Medicine. 2005 Sep 1;46(3):55-6.

Presenting Author: Louise Lennon Malbasha

Supervisor:Dr Emily Lostchuck

RELIABILITY OF TWO EQUINE BODY CONDITION SCORING SYSTEMS

Fox E 1 , Walshe N 2 , Duggan V 2 , Golding E 2

1 UCD School of Medicine, University College Dublin, Ireland

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

Obesity in horses is increasingly common and causes health problems like equine metabolic syndrome, musculoskeletal problems, and laminitis, which can be fatal. Body condition scoring is used to monitor a horse's weight quickly and simply and can be done by owners and vets. It provides insight into the horse’s wellbeing and its risk of developing weight related conditions

During this study 5 experts in equine health were asked to score 17 horses. They used 2 different systems, the Henneke and the Carroll & Huntington, each of which were repeated for a total of 4 scores for each horse by each assessor. This allowed an evaluation of repeatability (the same assessor assigns the same score to the same horse in the same condition more than once) and reproducibility (2 or more assessors assign the same score to the same horse in the same condition).

Results showed moderate to substantial intra-assessor agreement (Henneke: κ = .59 - .71, P < .001; Carroll & Huntingdon: κ = .64 - .66, P < .001) while inter-assessor agreement is good (Henneke: ICC = .78, P < .001; Carroll & Huntington: ICC = .76, P < .001) for both systems. This indicates that there is relatively good repeatability and reproducibility in equine body condition scoring, despite the subjective nature of the systems.

The results of this study will indicate the validity of the use of equine body condition scoring. This may affect the use of body condition scoring in clinical decisions and weight loss programmes.

Presenting Author: Ellen Fox

Supervisor: Ms Emma Golding

HOSPITAL ACQUIRED PNEUMONIA: 1 YEAR FOLLOW AUDIT TO ASSESS IMPACT OF HOSPITAL ACQUIRED PNEUMONIA PREVENTION CARE BUNDLE

Chee E 1 , Bright C 1 , Leahy D 2 , Linnane S 1, 2

1 UCD School of Medicine, University College Dublin, Ireland

2 Beacon Hospital, Respiratory Department, Dublin, Ireland

Hospital Acquired Pneumonia (HAP) is a nosocomial infection occurring in hospital patients 72 hours post admission. HAP has not been a focus for research due to its difficulties in prevention and diagnosis. HAP occurs frequently and often results in prolonged hospital stay, increased mortality, patient morbidity and higher healthcare cost.

The hospital database was searched for descriptions consistent with diagnosis of HAP. 1460 patients were identified and further analysed for clinical criteria consistent with HAP. 70 patients fit the criteria, 7 of which had COVID-19 during their stay which are excluded in this study. Variables examined were consistent with the baseline audit including white cell count, C-reactive protein (CRP) levels.

Risk factors for HAP are consistent with the baseline audit including low haemoglobin levels on admission (38 patients), presence of active cancer (20 patients), presence of cardiac disease (32 patients) as well as adverse outcome including high CRP levels and white cell count.

A HAP bundle was introduced following the baseline audit, as a result, HAP incidence rate has reduced (from 70 to 63), decreased severity of HAP can be seen from the declining average highest CRP levels (from 190.64 to 185.25). Number of ICU patients who were later diagnosed with HAP has trebled (from 8 to 21) however outcome has considerably improved with shorter length of stay, lower average highest CRP levels and ICU patient death.

Presenting Author: Ethan Chee

Supervisor: Dr Seamus Linnane

Co-Supervisor: Ms Donna Leahy

OBSERVATIONS OF A LONG COVID CLINIC: EFFECTS ON LUNG FUNCTION

Chang G 1 , Kalyansundaram K 1 , Dickson J 1 , Linnane S 1

1 UCD School of Medicine, University College Dublin, Ireland

The Long COVID condition affects an estimated one in 10 people infected with SARS-Cov-2 (COVID-19). 1 Despite a significant proportion of the population suffering from this condition, there is a very limited understanding of the pathophysiological effects of this condition towards lung function. This study aims to identify trends of Long COVID that may be helpful for future clinical reference and possible research.

This observational study looks at patients from the Beacon Hospital Long COVID outpatient clinic. Along with physiological tests, including pulmonary function tests (PFTs), questionnaires were sent out to each patient that required patients to detail their current medical status through SF36, HADS and Chandler fatigue scores. The patient’s data was then tabulated and analysed for correlation between symptoms and physical performance scores. Further analysis involved grouping patients based on age and gender was done to assess potential trends within each group.

Analysis of the data showed trends towards anxiety and depression in this group (overall >55% scored mild – severe anxiety /depression). Shortness of breath (MMRC ≥2) was reported in 50% of patients.

Correlation analysis did not show any link between results of questionnaires and physical assessment across genders or age groups presenting.

There was a high variability of symptom presentation of each individual patient presenting to clinic and we were unable to identify any pattern between symptom presentation and physical deficits in this Long COVID patient cohort. Further research looking at symptoms and physical exam considering different phenotypes of presentation may be more effective in identifying underlying pathologies in Long COVID patients.

Reference

World Health Organisation. ‘In the wake of the pandemic: Preparing for Long COVID’ Policy Brief, No.39. Copenhagen, Denmark: WHO Regional Office for Europe, 2021.

Presenting Author: Geoffrey Chang

Supervisor: Dr Seamus Linnane

CHARACTERISATION OF DECEASED PATIENTS WHOSE BLOOD SAMPLES WERE SENT TO THE MATER SUDDEN ADULT DEATH SYNDROME (SADS) BIOBANK

Brennan S 1 , McGorrian C 2 , Galvin J 2

1 UCD School of Medicine, University College Dublin, Ireland

2 Family Heart Screening Clinic, The Mater Misericordiae University Hospital, Dublin, Ireland

SADS refers to sudden death in the setting of a completely normal autopsy [1]. This research analysed autopsy reports of deceased individuals whose samples were sent to the Mater SADS Biobank, determining how many of these samples (a) are appropriate for molecular autopsy, (b) require screening of respective family members and (c) may be discarded.

Referring pathologists were asked to forward individual autopsy reports. These reports were systematically recorded following a defined data set focusing on details of lifestyle factors, pathology, cardiac anatomy, histology, toxicology and extracardiac causes of death.

Agreement between two reviewers regarding a cardiologist adjudicated (a) cause of death and (b) need for gene panel analysis was investigated. Regarding (a) cause of death, there was substantial interobserver agreement: Cohen’s Kappa = 0.73 (77.5% agreement, p<0.001). Both reviewers agreed that SADS, followed by coronary artery disease, followed by sudden unexpected death in epilepsy (SUDEP) were the most common causes of death. In total 14 SADS cases were identified: 10 by reviewer 1 (25%) and 13 by reviewer 2 (32.5%). Regarding (b) need for gene panel analysis, there was near perfect agreement: Cohen’s Kappa = 0.85 (92.5% agreement, p<0.001). Reviewer 1 identified 24 cases for gene panel analysis (60%), with reviewer 2 agreeing with 21 of these 24 cases (52.5%).

Post-mortem review of SADS biobank samples is essential to determine whether (a) family screening and (b) gene panel analysis is required. Of n=40, 60% of cases were deemed suitable by at least 1 reviewer for gene panel analysis.

Reference

Basso C, Aguilera B, Banner J, Cohle S, d’Amati G, de Gouveia RH, di Gioia C, Fabre A, Gallagher PJ, Leone O, Lucena J. Guidelines for autopsy investigation of sudden cardiac death: 2017 update from the Association for European Cardiovascular Pathology. Virchows Archiv. 2017, 471(6):691-705.

Presenting Author: Sophie Brennan

Supervisor: Prof Joseph Galvin

DETERMINING THE PREVALENCE AND NATURE OF CRITICAL INCIDENTS IN CHILD AND ADOLESCENCE MENTAL SERVICES: A SCOPING REVIEW

Dharmaraj K 1 , Hayden J 2 , Zahari Ashraf A 1 , McNicholas F 1 , Gavin B 1

1 UCD School of Medicine, University College Dublin, Ireland

2 School of Pharmacy and Biomolecular Sciences, Royal College of Surgens Ireland, Dublin, Ireland

The reporting of critical occurrences is a vital part of clinical management and is crucial for patient safety, safety of staff and healthcare quality assurance. Incident reporting includes the detection, reporting and analysis of events with the potential for harm. The aim of this scoping review was to identify and describe in existing literature the nature and prevalence of critical incidents within child and adolescent mental health services.

The scoping review followed Joanna Briggs Institute (JBI) methodology. Three electronic databases were searched and reported its findings according to PRISMA guidelines. The search strategy included all youth under 18. The context included any child mental health setting and services provided. The concept focused on critical incident reporting, any adverse event or near misses. For quality assurance a second reviewer screened 50% of the total 3494 studies. Followed by a full text review of 52 studies retrieved, with 6 studies charted.

Findings in one study suggested, the most common acts of critical incidents were seen to be staff assault, physical aggression, verbal assault, and threats. 1 Additionally, 2/6 of the selected studies reported a vast majority of critical incidents involved the same cohort of youth. For instance, (n =164/167; (98%)) had been involved in 70 or fewer incidents, (n=3/167 (2%)) were involved in more than 100 each. 2

Current findings indicate critical event reporting has promising benefits, such as assisting staff in analyzing current management practice. Further research is needed to develop policies and supports in primary and secondary child psychiatric healthcare systems.

References

O'Keeffe N, Gavin B, McNicholas F. Survey on critical incident reporting in a child and adolescent mental health service. Int J Risk Saf Med. 2013;25(1):33-8.

Boxer P. Aggression in very high-risk youth: examining developmental risk in an inpatient psychiatric population. Am J Orthopsychiatry. 2007;77(4):636-46.

Boxer P. Aggression in very high-risk youth: examining developmental risk in an inpatient psychiatric population. Am J Orthopsychiatry. 2007;77(4):636-46.

Presenting Author:Krithika Dharmaraj

Supervisor: Assoc Prof Blánaid Gavin

Co Supervisor: Prof Fiona McNicholas

SYSTEMATIC REVIEW OF REFERRALS TO CHILD AND ADOLESCENT MENTAL HEALTH SERVICE (CAMHS) DURING COVID-19

Yap S 1 , Lynch F 2 , McNicholas F 1, 2

1 UCD School of Medicine, University College Dublin, Ireland

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

There has been an increase in mental health presentations of youth to child and adolescent mental health services (CAMHS) following the Covid-19 pandemic. The purpose of this research is to examine pattern of referrals pre Covid-19 (2019) and post Covid-19 (Mar 2020- Jun 2022) and examine whether initial changes in 2020 have persisted. Following Ethics approval, all referrals to one geographically defined CAMHS catchment area were identified between March 2019 to June 2022. Clinical data was extracted from the electronic health records and anonymised for data entry and analysis

This study showed that in all accepted referrals, the mean age of the cohort over the years was 13 where females constituted majority of the referrals in post-Covid-19. There were significant increases in thoughts of self-harm (TSH)/suicidal ideation (SI), deliberate self-harm, Anxiety Disorders and Eating Disorders. The number of TSH/SI increased with each consecutive year after Covid-19. Referrals with concerns of possible mood disorder maintained pre-Covid base line levels while ADHD/ASD and behavioural disorder have fluctuated. Majority of accepted referrals throughout the years presented with internalising disorders with an average of 68% while externalising disorders presented with an average of 21%.

Number of referrals and accepted referrals/month had increased during the post Covid-19 period vs pre Covid-19. Given the sustained increase in referrals to CAMHS it is likely that patient waiting lists will begin to rise with resultant negative impact on youth mental wellbeing, in addition CAMHS’s staffs will also be more susceptible to burnouts due to increased work load.

Presenting Author:Sean Joash Yap Jun-U

Supervisor:Prof Fiona McNicholas

Co-Supervisor:Dr Fionnuala Lynch

EMERGENCY MENTAL HEALTH PRESENTATIONS TO CHILDREN’S HEALTH IRELAND (CHI) AT CRUMLIN DURING COVID-19

Sun B 1 , Moore K 2 , McNicholas F 1, 2, 3

1 UCD School of Medicine, University College Dublin, Ireland

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

3 Lucena Clinic Rathgar, St John of God Hospitaller Services, Dublin, Ireland

Following COVID-19 and associated restrictions, there has been an increase in psychological distress among youth in Ireland, with an increase of help-seeking to Child and Adolescent Mental Health Services (CAMHS) [1]. Hospital psychiatric admissions across five pediatric hospitals showed a 28.3% increase above prior-year levels in 2020 as initial lockdown restrictions were eased [2].

This study extends initial findings by examining the current emergency psychiatric presentations in CHI Crumlin Hospital in 2022 as COVID-19 becomes endemic and compare to the same time frame in 2021.

This is a retrospective cohort study covering two six-month periods from 1 st January 2021 to 30 th June 2021, and 1 st January 2022 to 30 th June 2022. Following ethical approval, data extraction from charts of patients with emergency psychiatric presentations were conducted. Data were compared using Welch’s t-test and chi-square tests.

A 30.2% decrease in number of acute psychiatric presentations in 2022 (120) were observed compared to 2021 (172). Presentations outside of normal working hours significantly decreased (60.5% vs 25.8%, p<0.001) as did onward discharge to CAMHS (87.8% vs 80.8%, p<0.001). With a non-significant increase of ADHD (20.3% vs 28.3%, p=0.114), a significant increase of youth on psychotropic medications (28.5% vs 33.3%, p=0.001) were observed.

The majority of clinical presentations were similar across timeframe with approximately 55% of suicidal ideation, 63% of deliberate self-harm, and 60% of depression or anxiety. Ongoing auditing of emergency psychiatric presentations is needed to examine whether the reduction observed in 2022 will continue.

Acknowledgements

The author would like to acknowledge the opportunity, time and guidance given from Prof. Fiona McNicholas, Dr. Kirean Moore, Dr. Kristen Maunder, Ms. Elisha Minihan and all members in CHI Crumlin psychiatry department.

References

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. 2021;7(3).

McDonnell T, Conlon C, McNicholas F, Barrett E, Barrett M, Cummins F et al. Paediatric hospital admissions for psychiatric and psychosocial reasons during the first year of the COVID-19 pandemic. International Review of Psychiatry. 2022;34(2):128-139.

Presenting Author:Bohan Sun

Supervisor:Dr Kirean Moore

Co-Supervisor:Prof Fiona McNicholas

IMPACT OF SUMOYLATION INHIBITOR (TAK-981) TREATMENT ON SARS-CoV-2 NUCLEOPROTEIN MULTIMERIZATION

Al Ghammari M 1 McLoughlin LE 2 , Gautier V 2

1 UCD School of Medicine, University College Dublin, Ireland

2 UCD Centre for Experimental Pathogen Host Research (CEPHR), School of Medicine, University College Dublin, Ireland

The COVID-19 pandemic has led to numerous ongoing consequences. However, the treatment options against SARS-CoV2 are still limited. Thereof, it is necessary to identify novel targets for drug development at the host-virus interface. Nucleocapsid protein (NP) is one of the structural proteins of the virus. NP multimerises and binds the viral RNA to form large ribonucleoprotein complexes during virion formation and packaging. A previous study in the lab has shown that NP undergoes SUMOylation, a post-translational modification in which SUMO (small ubiquitin-like modifier) protein is attached to lysine residues[1]. SUMOylation is fundamental in regulating protein-protein interactions, protein activity, stability, and translocation[2]. This study aimed to optimise formaldehyde fixation conditions to observe large NP multimers in the crosslinked samples, and to examine whether SUMOylation is involved in the multimerization of NP.

24 hours post-lipofectamine transfection with Flag-NP and HIS-SUMO-2, HEK293T cells were incubated with TAK-981 (50µM) for 5 hours. Next, they were fixed with 4% formaldehyde for 5 minutes and lysed with 4x Laemmli sample buffer.

Compared to control samples, western blot analysis of the treated conditions showed a 162% increase in the intensity of single NP bands concomitant with a 58% reduction in the intensity of large NP multimer bands (>300kDa). Reverse crosslinking confirmed equal amounts of NP in treated and control conditions.

The results show interference of NP multimerization in TAK981-treated cells, which implies that SUMOylation is likely to be involved in NP multimerization. This may set the basis for future drug development and biomolecular research related to SARS-CoV-2.

References

McLoughlin LE. The SARS-CoV-2 Nucleocapsid Protein: A Target for SUMOylation [Research Masters]. University College Dublin; 2021.

Geiss-Friedlander R, Melchior F. Concepts in sumoylation: a decade on. Nature Reviews Molecular Cell Biology. 2007; 8(12):947-956.

Presenting Author: Mohamed Al Ghammari

Supervisor: Assoc Prof Virginie Gautier

Co-Supervisor: Leah Ennis McLoughlin

DEVELOPING AN INFORMATION RESOURCE FOR PATIENTS UNDERGOING BARIATRIC SURGERY EXPLAINING THE IMPORTANCE OF ACTIVE MANAGEMENT OF IRON STATUS AFTER SURGERY

Narang R 1 , Gletsu-Miller N 2 , Docherty N 1

1 UCD School of Medicine, University College Dublin, Ireland

2 Indiana University School of Public Health, Bloomington, IN, USA

Bariatric surgery is a highly effective and safe treatment option for obesity. However, anatomical rearrangements to the stomach and small intestine can impair assimilation of dietary micronutrients. Hence, bariatric surgery confers a risk for the development or progression of a range of nutritional deficiencies [1]. Iron deficiency (ID) is common in bariatric surgery patients and frequently worsens following surgery in the absence of effective high-dose supplementation strategies [1]. Iron supplementation can also be poorly tolerated, and alongside an underappreciation of the consequences of ID, results in more than half of patients becoming iron deficient within 3 years of surgery [2]. The aim of this study was to develop an information resource for patients undergoing bariatric surgery and enhance medical literacy on post-operative management of bariatric surgery with respect to ID.

Here, an infographic will be created to aid the understanding and compliance of bariatric patients to iron supplementation. Following quantitative and qualitative feedback gathered from a focus group, the infographic will be finalized and distributed to multiple social media platforms of obesity related societies, bariatric surgery services and medical information hubs.

The focus group will consist of a brief presentation with knowledge-based questions before and after to compare the improvement of understanding of participants. Qualitative feedback gathered from participants will further improve the final infographic.

As a result, an appealing infographic catering to the general population will serve to improve medical literacy on post-bariatric surgery complications. Furthermore, prevention and treatment modalities for post-operative ID will be provided to potential bariatric surgery candidates.

References

Smith C, Herkes S, Behrns K, Fairbanks V, Kelly K, Sarr M. Gastric Acid Secretion and Vitamin B12 Absorption After Vertical Rouxen-Y Gastric Bypass for Morbid Obesity. Annals of Surgery. 1993;218(1):91-96

Vargas-Ruiz A, Hernández-Rivera G, Herrera M. Prevalence of Iron, Folate, and Vitamin B12 Deficiency Anemia After Laparoscopic Roux-en-Y Gastric Bypass. Obesity Surgery. 2008;18(3):288-293

Presenting Author: Rakesh Narang

Supervisor: Assoc Prof Neil Docherty

TRANSITION TO CLINICAL PRACTICE: EXPERIENCES OF INTERNATIONAL STUDENTS

Lee KE 1 , Higgins M 2 , Farran M 2

1 UCD School of Medicine, University College Dublin, Ireland

2 UCD Perinatal Research Centre, University College Dublin, National Maternity Hospital, Dublin, Ireland

Transitions can be defined as periods of change. Transitions in medical education are potentially complex, emotionally and socially dynamic. Three different types of transitions in medical education which are traditionally described: transition from preclinical to clinical training, from student to specialty training and from trainee to trained doctor. The aim of this study was to explore the transition of medical students from preclinical to clinical training, specifically from international students’ perspective.

The most appropriate research method was a scoping review, which was conducted following the Arksey & O’Malley and PRISMA guidelines. The most appropriate aim for this scoping review was “ to examine the extent, range and nature of research activity ”. The five steps of scoping review were completed including identifying the research question, identifying the relevant studies, study selection, charting the data, and lastly, collating, summarising and reporting the results.

Following a systematic search of PubMed, Embase and Scopus from 2010 to 2022, twelve full test papers met the criteria for review. Four general themes about the transition from preclinical to clinical training were identified: workload/time, patient contact, team relationship and gap in knowledge and skills. No research study compared the experiences or perceptions of international students compared to native medical students.

Future studies may explore possible differences between international and native medical students. We hypothesised that international students may have additional challenges in the transition but could not find any evidence of this being explored in the published medical education literature.

(246 words of 250 permitted)

Presenting Author: Kai En Lee

Supervisor: Dr Mary Higgins

Co-Supervisor: Dr Maria Farran

TRANSITION OF MEDICAL STUDENTS FROM PRE-CLINICAL TO CLINICAL EDUCATION: A SCOPING REVIEW FOCUSSING ON GENDER DIFFERENCES

Soobratty HF 1 , Farren M 1,2 , Higgins MF 1,2

1 UCD School of Medicine, University College Dublin, Ireland

2 UCD Perinatal Research Centre, University College Dublin, National Maternity Hospital, Dublin, Ireland

Medical students often describe the transition from the pre-clinical to clinical years as being challenging due to the numerous hurdles which need to be overcome in order to adapt to the new environment. The objective of this study is to identify any possible gender differences in this transition experience.

This scoping review follows the six-staged Arksey and O’Malley framework and aims to “examine the extent, range and nature of research activity” on the topic. 1 The PRISMA-ScR guidelines were followed to ensure completeness. The databases PubMed, Scopus and Embase were searched for the date filter: January 2010 to May 2022. A decision was made to restrict the search results to six journals with high impact factor, as was performed by Teunissen and Westerman in their earlier review. 2

The database search yielded 179 results. After reviewing titles, abstracts and full-texts, 11 articles were found relevant to this transition, of which two articles discussed gender differences. Studies demonstrated higher levels of self-reported anxiety, stress and depression from female students as opposed to their male counterparts. In comparison, males exhibited stronger feelings of excitement and confidence regarding the transition. A decrease in level of empathy in patient care was also observed among female students during the transition while the level for males remained steady.

The findings demonstrate that there exist gender differences, particularly with respect to the psychological impact of the transition. The results are however limited. Hence, the use of more structured psychological scales and diverse gender inclusion are potential future research avenues.

References

Arksey H, O'Malley L. Scoping studies: towards a methodological framework. International journal of social research methodology. 2005;8:19-32

Teunissen PW, Westerman M. Opportunity or threat: the ambiguity of the consequences of transitions in medical education. Medical education. 2011;45:51-59

Presenting Author: Hayfa Fatima Soobratty

Supervisor: Dr Mary Higgins

Co-Supervisor: Dr Maria Farren

TRANSITIONS IN MEDICAL EDUCATION: A SCOPING REVIEW FOCUSING ON THE TRANSFORMATION FROM DOCTOR IN TRAINING TO SPECIALIST

Ahmed M 1 , Farren M 1,2 , Higgins MF 1,2

1 UCD School of Medicine, University College Dublin, Ireland

2 UCD Perinatal Research Centre, University College Dublin, National Maternity Hospital, Dublin, Ireland

A sparsely documented phenomenon, the transition to consultant is an immensely important transformation in the career of any medic and one that carries arduous burdens. The objective of this study was to highlight the biggest barriers and impediments to achieving consultancy status in medicine.

Conducted in the style of a scoping review, this study followed Arksey H, O'Malley’s framework, producing “a synthesis of existing knowledge in the aim to map rapidly key concepts underpinning a research area” 1 . Embase, Pubmed and Scopus catalogues were searched from 2010 till 2022 with a restriction to six publications highlighted by Teunissen and Westerman 2 . The search process was also guided by the Preferred Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA).

After a preliminary search of 159 papers, 16 studies were found to be highly relevant to the subject matter and were selected for full reviews, which yielded a broad range of themes and concepts consistent with the transition into full specialist status which can be categorized into the five main subject matters of Burnout, Identity, Relationships, Leadership and Unpreparedness in general competencies.

The results suggest that the transition involves broad psychological factors which impinge on the trainee in the pursuit of specialist stature and shows that it is almost never a smooth, simple process. As a scoping study though, this study only aims to present an overview of material reviewed and cannot determine whether studies provide robust findings. Further research examining wider publications is a priority.

References

Arksey H, O'Malley L. Scoping studies: towards a methodological framework. International journal of social research methodology. 2005;8:19-32

Teunissen PW, Westerman M. Opportunity or threat: the ambiguity of the consequences of transitions in medical education. Medical education. 2011;45:51-59

Presenting Author: Mohamed Ahmed

Supervisor: Dr Mary Higgins

Co-Supervisor: Dr Maria Farren

THE TRANSITION TO MEDICAL STUDENT: A SCOPING REVIEW

Rae M 1 , Farren M 2 , Higgins M 2

1 UCD School of Medicine, University College Dublin, Ireland

2 UCD Perinatal Research Centre, University College Dublin, National Maternity Hospital, Dublin, Ireland

Transitions within the medical education continuum are periods of change in which students or doctors experience discontinuity which leads to the development of new behaviours 1 . Previous scoping reviews examining transitions within medical education mostly focused on transition from preclinical to clinical student and the transition from student to practitioner. The aim of this project was to complete a focused scoping review of the evidence on the transition to medical student.

Three databases, with focus on six specific medical education journals, were searched from 2010 to 2022 (PubMed, Embase and Scopus). The framework described by Arksey and O’Malley 2 was followed over six stages. Research was guided by the Preferred Reporting Items for Systematic reviews and Meta Analyses extension for Scoping Revie w (PRISMA-ScR) tool. Twelve papers were selected for review.

Studies primarily looked at the experience of the transition to being a medical student or interventions to support the transition. The key themes that were identified were social support networks, self-efficacy, social cohesion and professional identity. Reported interventions included in person and online pre-matriculating programs, peer-mentor programs and structured extended orientation.

Each of the themes identified were a crucial factor in the transition to medical school. Many of the studies focused on a subgroup of medical students such as “non-traditional’ and “at risk students” rather than the transition experienced by medical students as a cohort. The studies were primarily conducted in North America; future studies in Europe could address this gap in the literature.

References

Westerman M, Teunissen PW. Transitions in medical education. In K Walsh (Ed.), Oxford textbook of medical education (pp. 372–381) Oxford, UK: Oxford University Press, 2013

Arksey H, O'Malley L. Scoping studies: towards a methodological framework. International journal of social research methodology. 2005;8(1):19-32.

Presenting Author:Mary Rae

Supervisor:Dr Mary Higgins

Co-Supervisor:Dr Maria Farren

GP ACCESS TO DIAGNOSTIC IMAGING. A QUALITATIVE STUDY OF GPS’ EXPERIENCES

Gao J 1 , McCombe G 1 , Broughan J 1 , Fawsitt R, 1,2 , Collins C 3 , Feirteir M 4 , O’Callaghan M 3,5 , Quinlan D 3 , Stanley F 3 , Cullen W 1

1 UCD School of Medicine, University College Dublin, Ireland

2 Ireland East Hospital Group, Dublin, Ireland

3 Irish College of General Practitioners, Dublin, Ireland

4 Affidea Diagnostics, Ireland

5 School of Medicine, University of Limerick, Limerick, Ireland

Diagnostic imaging is commonly used in medicine to confirm diagnosis and allow for medical intervention and treatment of certain illnesses and injuries. In March 2021 the HSE introduced the Enhanced GP Access to Diagnostics initiative to implement direct access by GP referral to x-ray, CT, MRI, DEXA and ultrasound for the full adult population of Ireland via private companies and hospitals (1). This provided 138,000 additional scans by the end of 2021. The aim of this study was to conduct semi-structured interviews to qualitatively explore Irish general practitioners’ experiences and insights of having enhanced direct access to diagnostic imaging.

Ten GPs participated in semi-structured telephone interviews during June and July 2022 to elicit their experiences and insights of having direct access to diagnostic imaging. Interviews were audio recorded, transcribed verbatim and checked for accuracy prior to analysis. Thematic analysis was carried out as informed by Braun and Clarke (2) using NVivo V.12 software.

Four key themes were identified: (1) patient care management; (2) practice workload; (3) hospital referrals; (4) management of the scheme. All GPs acknowledged having enhanced direct access to scans improved patients' care management and access to diagnostic services. However, there were concerns regarding increased workload for GPs and consensus that policy and funding supports would be required to counter the additional practice workload that results from diverting patients from ED/AMU.

The study highlights the significance of GP direct access to imaging services. The results can inform future policy and development of direct access to diagnostic imaging services in Irish general practice.

Acknowledgments

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

References

Health Service Executive. Winter Planning within the COVID-19 Pandemic. 2020.

Braun V, Clarke V. What can “thematic analysis” offer health and wellbeing researchers? . Taylor & Francis. 2014.

Presenting Author: Jiaran Gao

Supervisor: Dr Geoff McCombe

Co-Supervisor:Prof Walter Cullen

LONG COVID IN GENERAL PRACTICE: EXPLORATORY MIXED-METHOD STUDY

Siu KYE 1 , Broughan J 1 , McCombe G 1 , Brennan J 2 , Collins C 3 , Fawsitt R 4,5 , Gallagher J 1 , Quinlan D 4 , Cullen W 1

1 UCD School of Medicine, University College Dublin, Ireland

2 Royal College of Physicians, Dublin, Ireland

3 Irish College of General Practitioners, Dublin, Ireland

4 Castle Gardens Surgery, Kilkenny, Ireland

5 Ireland East Hospital Group, Dublin, Ireland

Long COVID is a novel condition with wide-ranging clinical presentation. This study aims to explore General Practitioners’ perceptions of long COVID care by assessing the feasibility and acceptability of data collection, exploring issues GPs encounter when delivering long COVID patient care, and what could better support them.

This exploratory mixed-methods study is informed by a pragmatic theoretical framework with the STROBE(1) and SRQR(2) guidelines. Fifteen eligible GPs from the Ireland East Network were invited by post with a questionnaire included. In-depth semi-structured interviews were arranged upon receipt of questionnaire responses.

Nine GPs completed questionnaires and interviews. Four GPs agreed, four neither agreed nor disagreed, and one disagreed with the statement ‘I am satisfied with the COVID-19-related care at my practice’. Regarding initiatives, eight GPs wanted closer links with secondary services, eight wanted therapeutic initiatives, six wanted diagnostic supports, five wanted more patient input, two wanted more remote care and one suggested other. Three themes were generated from the interviews – clinical presentation, diagnostic uncertainty, and continual care. Findings suggest a highly variable clinical presentation, with an urgent need for clinical guidelines, assessment tools, and a multidisciplinary and integrated approach to optimise patient care.

This research is novel as it focuses on long COVID within the Irish GP setting. Study shows procedures were feasible and acceptable. The findings suggest that long COVID may be debilitating, and GPs are well-placed to address patients’ needs. Further research is needed to better understand challenges regarding the assessment, diagnosis, and continuing care of long COVID patients.

Acknowledgements

The author would like to thank the Health Research Board, the Ireland East Hospital Group and the UCD College of Health and Agricultural Sciences and School of Medicine.

References

Von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Bulletin of the World Health Organization. 2007;85:867-72.

O’Brien BC, Harris IB, Beckman TJ, Reed DA, Cook DA. Standards for reporting qualitative research: a synthesis of recommendations. Academic medicine. 2014;89(9):1245-51.

Presenting Author: Ka Yuet Emily Siu

Supervisor: Prof Walter Cullen

Co-Supervisor: Mr John Broughan

ENHANCED ACCESS TO DIAGNOSTIC IMAGING IN GENERAL PRACTICE: A SCOPING REVIEW OF PATIENT OUTCOMES

Phelan A 1 , Broughan J 1 , McCombe G 1 , Fawsitt R 1,2 , O’Callaghan M 3, 4 , Feirtear M 5 , Quinlan D 4 , Collins C 4 , Stanley F 4 , Cullen W 1,2

1 UCD School of Medicine, University College Dublin, Ireland

2 Ireland East Hospital Group, Dublin, Ireland

3 University of Limerick, Limerick, Ireland

4 Irish College of General Practitioners, Ireland

5 Affidea Diagnostics, Ireland

Direct access to diagnostic imaging in general practice provides an avenue to reduce referrals to consultant and to the emergency department services to ensure more timely diagnosis. Enhanced GP access to such services may potentially reduce hospital admissions, enhance patient care quality and improve disease outcomes [1]. This scoping review aims to gain a deeper understanding of how of direct access to diagnostic imaging in general practice impacts patient care and disease outcomes.

A search was conducted of ‘PubMed’, ‘Cochrane Library’, ‘Embase’ and ‘Google Scholar’ for papers published between 2012–2022 using Arksey and O’Malley’s framework for conducing scoping reviews [2]. The search process was guided by the ‘Preferred Reporting

Items for Systematic Reviews and Meta-Analyses’ (PRISMA).

Twenty-three papers were included. The studies spanned numerous geographical locations (most commonly UK, Denmark, and The Netherlands), encompassing several study designs (most commonly cohort studies, randomised controlled trials and observational studies), and a range of populations and sample sizes. Among the impacts reported were reduced referrals to specialist and emergency departments, cost-effectiveness, and patient satisfaction.

Our findings indicate that enhanced direct access to diagnostic imaging in general practice can improve clinical outcomes in specific patient populations. Further research is warranted to explore the impact of multiple imaging modalities on whole populations. Appropriate and readily accessible radiology referral guidelines were identified as a priority concern. These guidelines should guide policy makers when planning and implementing future direct access initiatives, thus ensuring that access to diagnostic imaging is harmonised and equitable for the whole population.

References

O'Riordan M, Doran G, Collins C. Access to diagnostics in primary care and the impact on a primary care led health service. 2015.

Arksey H, O'Malley L. Scoping studies: towards a methodological framework. International journal of social research methodology. 2005;8(1):19-32.

Presenting Author: Amy Phelan

Supervisor: Prof Walter Cullen

Co-Supervisor: Mr John Broughan

IMPROVING DETECTION AND MANAGEMENT OF FAMILIAL HYPERCHOLESTEROLAEMIA IN PRIMARY CARE: A SCOPING REVIEW

Khan AZ 1 , McCombe G 1 , McErlean S 1, 2 , Cullen W 1 , Brett T 3 , Gallagher J 1, 2

1 UCD School of Medicine, University College Dublin, Ireland

2 The Palms GP Surgery, Gorey, Wexford, Ireland

3 University of Notre Dame, Australia

Familial Hypercholesterolaemia (FH) is a genetic condition characterised by a lifelong elevation of low density lipoprotein cholesterol (LDL-c). FH is one of the most common genetic diseases, with an estimated global prevalence of 1 in 250 individuals (1). However, it is both underdiagnosed and undertreated (1). Primary care can be a valuable asset for the opportunistic detection and management of FH. This review examines the strategies for improving the detection and management of FH in primary care.

Six electronic databases (PubMed, The Cochrane Central Register of Controlled Trials, Web of

Science, CINAHL, ProQuest, and Scopus) were searched from May – June 2022 for articles published in English following Arksey and O’Malley’s six-stage scoping review process (2).

The initial search identified 1401 articles and a total of 30 studies were included in this review. A diverse range of methods have been studied for improving identification of FH. Three studies examined lipid outcomes from management in primary care. Two thirds of the studies with primary care management had a significant reduction in patient LDL-c levels.

The lack of consistency across the diagnostic criteria and the low number of studies addressing clinical outcomes are major features of this review. As a result, there is currently insufficient evidence to inform the most effective approach for the detection and management of FH in primary care.

Further research needs to be conducted to evaluate the effectiveness of the strategies for improving the detection and management of individuals with FH in primary care.

References

Wilemon KA, Patel J, Aguilar-Salinas C, Ahmed CD, Alkhnifsawi M, Almahmeed W, et al. Reducing the clinical and public health burden of familial hypercholesterolemia: a global call to action. JAMA cardiology. 2020;5(2):217-29.

Arksey H, O'Malley L. Scoping studies: towards a methodological framework. International journal of social research methodology. 2005;8(1):19-32.

Presenting Author: Abdullah Zafar Khan

Supervisor: Dr Joe Gallagher

Co-Supervisor: Dr Geoff McCombe

CLINICAL EFFECTIVENESS OF GENERAL PRACTICE BASED SELF-MANAGEMENT SUPPORT AMONG PATIENTS AT HIGH RISK OF CARDIOVASCULAR DISEASE: A SCOPING REVIEW

Grady E 1 , Broughan J 1 , McCombe G 1 , Morrissey J 2 , Treanor J 2 , Collins T 2 , Cullen W 1

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

2 Irish Heart Foundation, Dublin, Ireland

Cardiovascular diseases (CVD) are the leading cause of mortality worldwide, yet many of the risk factors that contribute to this mortality are modifiable. General practice (GP) and primary care-based interventions have demonstrated promise in enabling patients to self-manage CVD risk. However, knowledge regarding the clinical effectiveness of these interventions is limited and this review aims to address the gap.

A six-stage scoping review framework developed by Arksey and O’Malley [1] with revisions by Levac et al [2], was used. The search process was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses – Extension for Scoping Reviews (PRISMA-ScR).

Thirty-four studies were included. The studies investigated GP or primary care-based interventions to reduce patients’ CVD risk and / or mitigate the impact of CVD risk factors (uncontrolled diabetes mellitus, hypertension, hyperlipidaemia, and lifestyle factors such as diet, physical activity levels, smoking and alcohol consumption). Studies examined the efficacy and/or structure of the interventions. Clinical effectiveness was determined by improvement in systolic blood pressure, reduction in HbA1C levels and LDL cholesterol. Interventions involved nurse-led or lay personnel delivered initiatives, follow-up care, patient education, motivational interviewing and goal setting, medication adherence, accessibility of patient information leaflets, and access to additional supports such as smoking cessation or dietitian services.

Despite noted improvements in some of the studies, most of the results of these interventions thus far have not been statistically significant. Further large-scale and long-term studies are required to adequately assess the impact of these supports on high-risk patients.

Acknowledgements

The author would like to acknowledge funding from the family of the late Dr Mary J Farrell and the University College Dublin Ad Astra Academy.

References

Arksey, H. and L. O'Malley, Scoping studies: towards a methodological framework. International Journal of Social Research Methodology, 2005. 8(1): p. 19-32.

Levac, D., H. Colquhoun, and K.K. O'Brien, Scoping studies: advancing the methodology. Implementation Science, 2010. 5(1): p. 69.

Levac, D., H. Colquhoun, and K.K. O'Brien, Scoping studies: advancing the methodology. Implementation Science, 2010. 5(1): p. 69.

Presenting Author: Emma Grady

Supervisor: Mr John Broughan

Co-Supervisor: Prof Walter Cullen

REDUCING READMISSIONS IN OLDER ADULTS THROUGH PRIMARY CARE INTERVENTIONS: A SCOPING REVIEW

Ossman J 1 , McCombe G 1 , Fawsitt R 2 , Doran P 1 , Queally M 3 , Lyons D 2 , Lynch T 1 , Merlin K 4 , Cullen W 1

1 UCD School of Medicine, University College Dublin, Ireland

2 Ireland East Hospital Group, Dublin, Ireland

3 Health Services Executive, Ireland

4 University of Puerto Rico, Puerto Rico

Hospital readmission is an important challenge for health services and is associated with increased healthcare costs and adverse health outcomes (1). Older adults are at high risk of readmission and targeting interventions to reduce readmissions is a priority. This review aims to examine primary care interventions designed to reduce readmissions among older adults.

The scoping review utilised Arksey and O’Malley’s six-stage framework (2). The search process was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Electronic database searches were performed on PubMed, the Cochrane Library and Google Scholar during June and July 2022. Thirty-four studies were considered relevant and included in the review. Interventions were grouped thematically based on the type of intervention used.

All the included studies involved an intervention aimed at older adults and patients with specific chronic diseases (most commonly congestive heart, COPD, and type II diabetes mellitus). A range of methodologies were used in the selected studies, most commonly randomized controlled trials. The most common interventions related to primary care physician visits either pre- or post-discharge, and either clinic or home based.

While the review did have some positive findings regarding post-discharge visits, there is no definitive evidence suggesting which interventions have the most beneficial effect on lowering readmission rates. Further research in this area is warranted.

References

Jencks SF, Williams MV, Coleman EA. Rehospitalizations among Patients in the Medicare Fee-for-Service Program. New England Journal of Medicine. 2009;360(14):1418-28.

Arksey H, O'Malley L. Scoping studies: towards a methodological framework. International journal of social research methodology. 2005;8(1):19-32.

Arksey H, O'Malley L. Scoping studies: towards a methodological framework. International journal of social research methodology. 2005;8(1):19-32.

Presenting Author: Janourine Ali Hassan Ossman

Supervisor: Dr Geoff McCombe

Co-Supervisor: Prof Walter Cullen

EXPLORATION OF INTERCULTURAL COMPETENCE AMONG RADIOGRAPHY STUDENTS AND PRACTICE EDUCATORS

Lawati Z 1 , McGee A 2 , Davis M 2

1 UCD School of Medicine, University College Dublin, Ireland

2 UCD Radiography and Diagnostic Imaging, UCD School of Medicine, University College Dublin, Ireland

Ongoing changes in migration patterns have increased both national and ethnic diversities across populations. As a result, the concept of cultural competence has gained attention amongst all healthcare practitioners, including radiographers, to ensure quality healthcare delivery to diverse patient groups. Cultural competence in medicine is described as the understanding of the interaction between social and cultural factors with the health beliefs and behaviours of patients 1 . This study aimed to explore the attitudes and opinions of radiography students and practice educators regarding cultural competence relative to their professional role as radiographers.

Three focus group sessions were conducted with radiography practice educators (2 sessions) and undergraduate radiography students (1 session). These were held online via the Zoom platform. Data collected during participant discussions was analysed according to Braun and Clarke’s six phases of thematic analysis 2 .

Seven individuals participated; 2 students and 5 practice educators. Thematic analysis identified variation among participants in their definition and experience of cultural competence relative to their professional role as radiographers. Issues such as obtaining consent and language barriers were themes frequently highlighted by participants, with the majority also acknowledging insufficient academic and clinical practice-based learning relative to managing cultural challenges in the healthcare setting.

Diversifying the student groups sent to clinical placement sites, weekly reflective sessions discussing the cultural challenges encountered and providing booklets containing frequently asked questions for radiography examinations in the most common languages spoken by presenting patients could increase students’ cultural competence and subsequently, the quality of healthcare provided.

References

Kaihlanen A-M, Hietapakka L, Heponiemi T., (2019). Increasing cultural awareness: Qualitative study of nurses’ perceptions about cultural competence training. BMC Nursing , 18, 38, pp1-9.

Braun, V. and Clarke, V., (2006). Using thematic analysis in psychology. Qualitative Research in Psychology , 3(2), pp.77-101.

Presenting Author: Zahra Al Lawati

Supervisor: Dr Allison McGee

Co-Supervisor: Dr Michaela Davis

DECIPHERING DONOR- AND CELL-TYPE-SPECIFIC INTERACTIONS BETWEEN SCHIZOPHRENIA GENETIC RISK VARIANTS

Mennie KM 1 , Townsley KG 2 , Dobrindt K 3 , Brennand KJ 3

1 UCD School of Medicine, University College Dublin, Ireland

2 Icahn School of Medicine at Mount Sinai, New York, NY, USA

3 Yale University School of Medicine, Yale University, New Haven, CT, USA

Schizophrenia (SCZ) is a polygenic neuropsychiatric and neurodevelopmental disorder [1]. The genetic liability for SCZ is largely due to non-coding, common variants which interact dynamically with genotype and environment [2]. Polygenic Risk Scores (PRS) estimate an individual’s genetic liability for a particular disease. Here, we investigate the transcriptomic differences between individuals with a high or low SCZ PRS but without a psychiatric diagnosis. In particular, we explore the effects of genetic background on gene expression in different brain cells – namely, astrocytes, GABAergic neurons, glutamatergic neurons, and neural progenitor cells – derived from human-induced pluripotent stem cells (hiPSCs).

We performed differential gene expression analysis comparing high versus low SCZ PRS donors for each cell type using Limma and EdgeR. We then conducted a meta-analysis (METAL) of the DGE results to identify changes in gene expression shared across cell types. To identify convergent biological pathways, we performed Gene Set Enrichment and Over Representation Analyses.

Few significantly differentially expressed genes (DEGs) overlapped between the different cell types while expression of DEGs was associated with distinct developmental periods. Our analyses suggest a particularly important role for GABAergic neurons during late prenatal brain development and middle adulthood. Shared gene expression converged on epigenetic and developmental pathways.

Here, the utility of hiPSC models in deciphering the donor- and cell-type-specific interactions between SCZ genetic risk variants is demonstrated. Because such interactions have important implications for susceptibility or resistance to SCZ, such studies pave the way to precision medicine and the identification of therapeutic interventions tailored to the individual.

References

Henriksen MG, Nordgaard J, Jansson LB. Genetics of Schizophrenia: Overview of Methods, Findings and Limitations. Front Hum Neurosci . 2017;11:322.

Rajarajan P, Flaherty E, Akbarian S, Brennand KJ. CRISPR-based functional evaluation of schizophrenia risk variants. Schizophr Res . 2020;217:26-36.

Presenting Author: Katrina Mennie

Supervisor: Dr Kristen Brennand

SEXUALLY TRANSMITTED DISEASES IN IRELAND DURING THE 19 TH AND 20 TH CENTURY

Tan J 1 , Cox C 2

1 UCD School of Medicine, University College Dublin, Ireland

2 UCD School of History, Newman Building, University College Dublin, Ireland

Sexually transmitted diseases (STD) are a fascinating part of medical knowledge. With diseases such as the Human Papilloma Virus (HPV), Chlamydia, Gonorrhea and Syphilis known to the general population today. However medical knowledge was not as advanced during the 1800s to 1900s. This compounded with the fact that sexual education was not widely taught during that time led to a rise in STDs, known as Venereal Diseases, in that time. This study looks at both primary and secondary sources to better understand the climate of Ireland during this time. The study would then try to formulate a better understanding of venereal diseases, how the Irish public viewed them and ultimately what could be learnt from history.

Presenting Author: Joshua Tan Tai Kuang

Supervisor: Assoc Prof Catherine Cox

PROFILING CIRCADIAN OSCILLATION IN PPARα mRNA EXPRESSION IN RAT RENAL PROXIMAL TUBULAR CELL CULTURE

Nino AG 1 , White J 1,2 , Docherty NG 1,2

1 UCD School of Medicine, University College Dublin, Ireland

2 UCD Diabetes Complications Research Centre, Conway Institute, University College Dublin, Dublin, Ireland

Peroxisome proliferator activated receptor alpha (PPARα) serves as the target of the fibrate class of lipid-lowering drugs. PPARα expression and activity in the liver are influenced by the cellular clock [1] possibly reflecting its role in governing circadian patterns of energy metabolism. We aimed to characterize the circadian oscillation in Pparα expression in cultured rat renal tubular cells (NRK-52E) in order to identify a time window during which responses to fenofibrate treatment might be maximal.

NRK-52E cells were cultured to confluence, and according to an established method of synchronizing the cellular clock. Cells were treated for 2 hours with 100nm Dexamethasone then left to synchronize for 24 hours [2] . Ethanol vehicle treated cells served as a control. Cells were harvested at: 3, 11, 15 and 23 hours post synchronization, and cDNA was synthesized from RNA isolates. Then qPCR was performed using Pparα, Bmal1 and Per2 primers, the latter two are cellular clock genes, which show a reciprocal pattern of expression which can be assessed as evidence of the retention of circadian rhythms of gene expression in cultured cells. Two independent experiments were undertaken with internal replicates. The relative quantity of each gene was calculated using the ΔΔCt method using the 3-hour ethanol vehicle treated group as a calibrator.

In dexamethasone treated cells, the peak expression of Pparα was found at 3 and 23 hours post synchronization. However, this profile was also observed in vehicle treated cells. Moreover, dexamethasone appeared to ablate the normal reciprocal relationship of the Bmal1 and Per2 genes observed in vehicle treated cells.

The intrinsic Pparα oscillation implies that there may be a promising associated impact on the pharmacodynamic of fenofibrate treatment, a potentially renoprotective therapy in type 2 diabetes.

Acknowledgments

The author would like to acknowledge the opportunity, time and guidance provided by Assoc Prof Neil Docherty and James White.

References

Chen L, Yang G. PPARs Integrate the Mammalian Clock and Energy Metabolism. PPAR Research [Internet]. 2014 [cited 2022 Aug 6];2014:1–6. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3945976/

Gaspar LS, Álvaro AR, Carmo‐Silva S, Mendes AF, Relógio A, Cavadas C. The importance of determining circadian parameters in pharmacological studies. British Journal of Pharmacology [Internet]. 2019 Jul 6 [cited 2022 Jul 5];176(16):2827–47. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6637036/

Presenting Author: Abdallah G. Nino

Supervisor: Assoc Prof Neil G. Docherty

Co-Supervisor: Mr James White

THE EFFECT OF ANTISENSE OLIGONUCLEOTIDE THERAPY IN A MOUSE MODEL OF HUNTINGTON’S DISEASE

Matthews M 1 , Tsanov M 2

1 UCD School of Medicine, University College Dublin, Ireland

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

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease caused by CAG trinucleotide repeats in the huntingtin (HTT) gene on chromosome 4. A possible treatment for mutations in the HTT gene is anti-sense oligonucleotide therapy (ASO) which leads to a reduced amount of mutant HTT.

The aim of this research was to investigate the impact of ASO therapy on the navigational behaviour of experimental mice in a Barnes Maze. Three parameters assessed spatial learning: primary errors, hole deviation, and the angle of approach from initial position to the escape hole. Three groups of mice (ASO-treated, n=16; wild type, n=12; vehicle-treated, n=13) were compared over ten days of acquisition training. The data was analysed with a two-way ANOVA test, and groups were compared with Bonferroni’s multiple comparison test.

ASO treatment induced a non-significant trend in all three parameters. The ASO treated mice improved their average angle of approach from Day 1 (94°) to Day 10 (82°). Primary errors did not improve; hole deviation improved slightly from Day 1 (4.19) to Day 10 (3.44). However, the difference between the ASO and vehicle treated group was not statistically significant on any of the ten days of training.

This study suggests that ASO therapy’s improvement in navigational accuracy is not sufficient to induce therapeutic change. The use of Barnes maze to assess the behavioural improvement with ASO therapy may not be representative of a mouse’s improved cognitive abilities. Further studies with a different mouse model and longer period of assessment should be considered.

Reference

Southwell AL, Kordasiewicz HB, Langbehn D, Skotte NH, Parsons MP, Villanueva EB, et al. Huntingtin suppression restores cognitive function in a mouse model of Huntington’s disease. Science Translational Medicine [Internet]. 2018 Oct 3 [cited 2020 Apr 22];10(461). Available from: https://stm.sciencemag.org/content/10/461/eaar3959.abstract

Presenting Author: Miriam Matthews

Supervisor: Dr Marian Tsanov

BIOMARKER DISCOVERY PREDICTING & MONITORING RESPONSE TO THERAPY

Hegarty N 1 , O’Neill A 1 , Dillon E 2 , Scaife C 2 , Cagney G 2 , Watson W 1

1 UCD School of Medicine, University College Dublin, Ireland

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

Treatment options for localized high-risk prostate cancer (PC) include surgery or radiation therapy, often optimized with neoadjuvant hormone therapy. Abiraterone acetate (AA) is an inhibitor of testosterone production. This study examines the addition of AA with GnRH agonist pre-radiation therapy. The primary objectives of this pilot study were to explore biomarker patterns to predict treatment response. The secondary objectives were to select the best biological matrix (serum or plasma) to detect these biomarkers and identify the most appropriate liquid chromatography mass spectrometry (LC-MS) approach to use.

We collected serum and plasma samples from 44 patients, with associated prostate specific antigen (PSA), testosterone & oestradiol levels, across five treatment timepoints. Post-treatment PSA below 0.1 ng/mL was deemed a successful response. We processed day zero plasma and serum samples for two patients (four total), using the iST proteomic sample preparation kit before analyzing with two LC-MS modalities, TimsTOF & QExactive.

Responders (n=32) showed lower initial Gleason scores (GS) versus non-responders (n=12), [GS 7/8 = 68.75% versus 41.66% respectively). The testosterone and oestradiol profiles were similar between groups. There was a similar number of proteins detected in serum and plasma (241 vs 239 respectively). The QExactive modality detected 228 proteins compared to TimsTOF’s 161 proteins.

Preliminary analysis has identified an association between GS and PSA response and that this response appears to be independent of hormone changes. QExactive represents the most sensitive LC-MS technology and neither sample type had a clear advantage for biomarker detection. We have identified potential proteins of interest for future studies.

Presenting Author: Nicholas Hegarty

Supervisor: Prof William Watson

EQUITY ORIENTED PAIN MANAGEMENT FOR PEOPLE WHO USE DRUGS: A SCOPING REVIEW

Qiu LR 1 , Narayan S 2 , Maclure M 3 , McCracken R 2 , Klimas J 2

1 UCD School of Medicine, University College Dublin, Ireland

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

3 Therapeutics Initiative, Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver BC, Canada

Overdose health emergencies continue to drive drug-related mortality and morbidity. The recent changes in prescribing guidelines recommend prescribing fewer opioid analgesics and increasing non-opioid/non-pharmacological approaches. However, people who use drugs (PWUD) have been disproportionally affected by adverse events (opioid-related emergency department visits or hospitalizations) due to rapid reduction of opioids [1]. Furthermore, vulnerable groups, such as PWUD continue to experience barriers to accessing non-opioid pain management therapies. This scoping review identified the processes that limit access to the full spectrum of pain management therapies for PWUD.

We followed the Arksey and O’Malley scoping review method [2]. We generated search criteria for PubMed (MEDLINE) related to chronic pain, analgesics, abuse and equity-related terms. Our inclusion criteria included studies published since 2016 whose population was adult PWUD seeking pain management.

The electronic search identified 668 citations. After screening, 10 studies were included. Three major themes emerged from our scoping review 1) non-pharmacological treatments are effective, but barriers related to geography, physician knowledge, healthcare infrastructure, and most significantly cost exist. 2) The stigma of being a PWUD leads to poor patient-physician communication which led to denial of adequate prescription opioids 3) Suboptimal pain management led to patients being their own pain management specialists and resulted in increased illicit drug use, propagating a cycle of inadequate pain management.

This review identified several barriers that prevent PWUD from accessing a full range of pain management. PWUD, who experience pain in higher rates than the normal population, must receive equitable healthcare.

Acknowledgements

The author would like to acknowledge funding from the UCD SSRA International Dean’s Scholarship

References

Mark TL, Parish W. Opioid medication discontinuation and risk of adverse opioid-related health care events. Journal of substance abuse treatment. 2019 Aug 1;103:58-63.

Arksey H, O'Malley L. Scoping studies: towards a methodological framework. International journal of social research methodology. 2005 Feb 1;8(1):19-32.

Presenting Author:Lily Qiu

Supervisor:Dr Jano Klimas

Co-Supervisor:Dr Rita McCracken

WHAT TREATMENT OPTIONS DO PATIENTS WITH OBESITY COMPLICATIONS PREFER?

Walley D 1 , Craig H 2 , Le Roux CW 1,2

1 UCD School of Medicine, University College Dublin, Ireland

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

Obesity is recognised as a disease with more than 220 different complications including type 2 diabetes (T2D), chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD), all of which contributes to an increased in mortality. Patients presenting with obesity complications face challenges when deciding on treatment options for their disease. We aimed to understand the patients’ perspective of treatment options and what influences their decision.

We used photovoice, a form of participatory action research. We recruited six patients with obesity complications. 2 Over two weeks, patients took photos representing their concerns of living with obesity complications, their hopes and desires from engaging in treatment. Interviews were then conducted with patients to discuss the images. We then completed a thematic analysis.

The overarching themes observed based on photovoice were self-blame about the participant’s weight compounded by a lack of support from health care professionals. Physical and emotional factors included a lack of mobility and anxiety impacting their intrapersonal environment. Treatment choice was a universal theme for all participants with the majority expressing concerns in respect to access, availability, cost and side effects. The majority preferred nutrition-based therapy with a minority choosing pharmacotherapy or surgical therapy.

Participants outlined their preferences for treatment and the factors which influence that process. The voice of patients with obesity complications needs to be considered when planning healthcare policy, guidelines, and services. Assessing factors that influence a patient’s choice about treatment will inform service providers and enable providers to address patient concerns and barriers to treatment.

References

Ansari S, Haboubi H, Haboubi N. Adult obesity complications: challenges and clinical impact. Ther Adv Endocrinol Metab. 2020,11:2042018820934955.

Creswell J. Educational Research: Planning, Conducting, and Evaluating. 4th ed. Boston: Pearson; 2012.

Presenting Author: David Walley

Supervisor:Prof Carel le Roux

Co-Supervisor:Ms Hilary Craig

USING QUALITATIVE BEHAVIOURAL ASSESSMENT TO EVALUATE MOUSE BEHAVIOUR AS AN INDICATOR OF CHRONIC VERSUS ACUTE PAIN

Marin F 1, 2 , Martin M 1 , Mehigan S 3 , d’Alton M 3 , Reynolds AL 2, 4

1 UCD School of Medicine, University College Dublin, Ireland

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

3 UCD Biomedical Facility, University College Dublin, Ireland

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

The use of live animals in research is a controversial topic with the question of welfare at the forefront of discussions around the topic. There are many well-researched methods of measuring welfare in research animals, but many of them are invasive, require an extensive habituation period, or are only useful for measuring acute pain and not spontaneous/chronic pain. Qualitative behavioral analysis (QBA) is a relatively novel methodology being used to evaluate both acute and spontaneous/chronic pain in various species by evaluating the behaviours of the individuals to get an idea of their emotional and physical state. QBA is of particular interest as it is non-invasive, can be performed regardless of the research the animals undergo, and may allow observers to identify subtle expressions of pain a prey species might hide when observed via other methods. This project seeks to determine if QBA is a valid methodology for the assessment of chronic and acute pain in laboratory mice.

QBA was conducted retrospectively using pre-recorded videos of mice undergoing experiments. The two studies examined were seven weeks long and had ten and eleven mice in the experiments, respectively. Videos of the mice in their cages were taken twice a week (Monday and Friday) over 7 weeks, with an invasive procedure performed after the first recording. Nineteen fixed terms were used to attribute a score along a visual analogue scale for each mouse from minimum to maximum expression of the behaviors associated with each term to create a holistic picture of each individual animal.

A Shapiro-Wilk Test proved the data to be not normally distributed, identifying it as non-parametric.

An analysis was made of all 19 fixed terms across the timecourse of the experiment. Fixed terms associated with positive behavioural indicators such as “energetic”, “playful”, “determined”, “inquisitive”, “comfortable” and “content”, decreased over time, with a sharp decrease seen in weeks 6 and 7. Terms associated with negative behavioural indicators such as “agitated”, “tense”, “anxious” and “in pain” similarly increased towards the end of the experiment. Inter-assessor reliability testing will be performed.

Data suggests a difference in the behavioural expressions of mice at the start and end of the procedure which may highlight the ability of QBA testing to discriminate between acute and chronic painful states, however more testing must be performed.

Presenting Author: Fara Marin

Supervisor:Dr Mark d’Alton

Co-Supervisor:Dr Alison L Reynolds

EFFECT OF SARS-CoV-2 VARIANT ON LONG COVID SYMPTOMOLOGY

Kalyansundaram K 1 , Chang G 1 , Dickson J 1,2 , Linnane S 1,2

1 UCD School of Medicine, University College Dublin, Ireland

2 UCD Beacon Hospital Academy, Dublin, Ireland

Long COVID is defined by the World Health Organisation as persistent symptoms that cannot be explained by an alternative diagnosis following acute SARS-CoV-2 infection [1]. The pathophysiology is not understood with both biological and psychosocial aetiological mechanisms being proposed. We hypothesised that a biological process would result in different symptom profiles following acute infection with different SARS-CoV-2 variants.

Patients (n=353) referred to the Long COVID Clinic at the Beacon Hospital (47 males, 118 females, & 1 unspecified sex) completed symptom questionnaires. We reviewed variant data produced by the Health Protection Surveillance Centre [2] and defined Alpha variant infections occurring between 1/1/2021 and 31/5/2021 (n=79), Delta variant infections from 1/7/2021 to 30/11/2021 (n=62) and Omicron variant infections from 1/1/2022 onwards (n=25). Patient questionnaire data was analysed to identify differences in symptom prevalence according to variant infection.

Fatigue, breathlessness, sleep disturbance, anxiety & depression, and chest discomfort were the commonest symptoms across all variants. Myalgia, palpitations, brain fog, olfactory disturbance and headache affected a significant minority of patients. Fatigue, palpitations, brain fog and headache became less prevalent as the pandemic progressed while anxiety & depression, sleep disturbance, chest discomfort and olfactory disturbance increased. Breathlessness remained relatively consistent.

Long Covid triggered by different variants produces broadly similar symptoms. There are differences in the relative proportions of symptoms. This may indicate that differences in the acute infection trigger a different biological response and inform the search for a pathophysiological mechanism of Long Covid.

References

Long COVID: WHO issues clinical case definition [Internet]. www.medicalnewstoday.com . 2021 [cited 2022 Jun 7]. Available from: https://www.medicalnewstoday.com/articles/who- issues-clinical-case-definition-of-long-covid#The-WHO-definition

Summary of COVID-19 virus variants in Ireland [Internet]. 2022 Jul [cited 2022 Aug 1]. Available from: https://www.hpsc.ie/az/respiratory/coronavirus/novelcoronavirus/surveillance/summaryofcovid- 19virusvariantsinireland/COVID_19_weekly_variant_report_website_20220626-final.pdf

Presenting Author:Kiranmala Kalyansundaram

Supervisor:Dr Seamus Linnane

Co-Supervisor:Ms Jane Dickson

A COMPARISON OF CYATHOSTOMINS SPECIES POPULATION BETWEEN CLINICALLY NORMAL HORSES AND HORSE WITH ACUTE LARVAL CYATHOSTOMINOSIS USING MOLECULAR ANALYSIS

O’Neill F 1 , Gangotia D 1 , Zintl A 1 , Kiser L 1, 2 , Boxall O 1 , McSweeney D 1, 2 , Dunne S 1 , Lamb BR 1 , Walshe N 1 , Mulcahy G 1 , Byrne O 1 .

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

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

Cyathostomins are a parasitic nematode of the gastrointestinal tract impacting the equine population worldwide. There are over 40 species of cyathostomins, often occurring in mixed infections. Chronic and acute cyathostomins have disease implications, specifically acute larval cyathostominosis (ALC) has a poor prognosis. Conventionally, morphology methods was used to differentiate cyathostomin species. However, morphological identification is labor-intensive and requires expertise. Thus, molecular speciation can contribute to a better understanding of the species involved in the clinical disease. This study characterizes cyathostomin species through molecular speciation.

Cyathostomin worms were harvested from the caecum, right ventral colon, and left dorsal colon of 11 horses with no clinical signs and 1 horse that was euthanized due to ALC. Specifically, our work investigated worms from 2 clinically normal horses and the horse with ALC. DNA extraction from individual worms was performed. Following extraction, the ITS-2 region of worms was amplified and run on gel electrophoresis. Sequences were input into the Basic Alignment Search Tool for species determination.

We identified twelve cyathostomin species and one large strongyle species, Strongylus vulgaris. Interestingly , this study revealed that the non-clinical cases demonstrated a mixture of cyathostomins, whereas the horse suffering from ALC had only one species, Cylicocylus insigne .

Application of molecular speciation of cyathostomins is a valuable technique to understanding the possible contribution of species type to clinical disease. We provide a dataset that highlights the need for further investigation into the species-specific role in cyathostominosis and the varying pathogenicity of each species.

Presenting Author: Fiona O’Neill

Supervisor: Dr Nicola Walshe

Co-Supervisor: Prof Grace Mulcahy

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