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


figure a
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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 H1

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

2Institute 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.

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 O1, Buggy P2, Smith G3, Inzitari R3, Wall T4, Buggy DJ1, 3, 4, 5, 6

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

2School of Medicine, University College Cork

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

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

5Outcomes Research, Cleveland Clinic, OH, USA

6EU COST Action 15204 Euro-Periscope

Some experimental and retrospective clinical studies signal an association between certain anaesthetic techniques and tumour metastasis following breast cancer surgery1,2. 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.

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

1.

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.

2.

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

1UCD School of Medicine, University College Dublin, Ireland

2Cachamsi, 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.

1.

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

1UCD School of Medicine, University College Dublin, Ireland

2UCD 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 C1,2, McGrane N2, Keyes LM2

1UCD School of Medicine, University College Dublin, Ireland

2Health 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.

1.

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

2.

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 S1, 2, Lu JYS1,2, Doyle, C1,2, Gars M1,2, 3, Thorpe SD1,2

1UCD School of Medicine, University College Dublin, Ireland

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

3École 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 1×106 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.

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.

1.

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 LYS1,2, Xavier S1,2, Doyle C1,2, Thorpe SD1,2

1UCD School of Medicine, University College Dublin, Ireland

2UCD 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 chemoresistance1 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.

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.

1.

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.

2.

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 JA1, Agoni C2, Shields D2

1UCD School of Medicine, University College Dublin, Ireland

2UCD 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 E4, Vartak T1, Moran B2, Kennedy C1, Barry M3, Godson C1, Brennan E1

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

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

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

4UCD 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 K1, Gilmore J2, McGettrick S3, Froehlich R3, Flaherty AM3, Ó’Muireagáin C3, Harte C3, Fagan S4, Sheehan M5, O’Shaughnessy J6, Mee J7, Keady T8, Zintl A1

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

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

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

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

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

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

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

8Teagasc, 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.

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

1.

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

2.

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

1UCD School of Medicine, University College Dublin, Ireland

2Department 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/m2, 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, X2 (1, N=112) =5.72, p=.0168, and X2 (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

1UCD 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 bodyweight1, 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 intervention2. 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.

1.

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

2.

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 E1,2, George TP 2,3,4,5, Sorkhou M2,3,4

1UCD School of Medicine, University College Dublin, Ireland

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

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

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

5Addictions 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, np2=0.544) and were not significantly affected by contingent reinforcement (F(1,3)=0.475, p=0.540, np2=0.137).

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

1.

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 T1, Dunbar P2, Behan L2, Keyes LM2

1UCD School of Medicine, University College Dublin, Ireland

2Regulation 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.

1.

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 AAHA1, Farren M1, and Higgins M1

1UCD 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.

1.

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/

2.

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 A1, Jones L2,3, Bond J1,2,3,4

1UCD School of Medicine, University College Dublin, Ireland

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

3National Children's Research Centre, Dublin, Ireland

4Children'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.

1.

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

1UCD School of Medicine, University College Dublin, Ireland

2School 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

UNDERSTANDING THE ROLE OF NON-HLA ANTIBODIES IN RENAL TRANSPLANT

REJECTION: A RETROSPECTIVE CASE-CONTROL COHORT STUDY

Jameel IK1, de Chickera SN2, Sidahmed A2

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

2University 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.

1.

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

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