27 minute read
Variability of Ventilation Outcome Measures using Hyperpolarized 129
Xenon MRI in Children with Primary Ciliary Dyskinesia
Layan M. Bashi, Jonathan Rayment, Rachel Eddy, Sharon D. Dell
Primary Ciliary Dyskinesia (PCD) is a genetic disorder causing recurrent lower respiratory infections and lung damage. Current lung function tests lack sensitivity for early detection, necessitating improved tools. Hyperpolarized 129 Xenon MRI (XeMRI) offers a sensitive technique for visualizing and quantifying lung ventilation using the Ventilation Defect Percent (VDP) as the primary outcome measure. However, XeMRI’s short-term variability in children with PCD is unestablished. This study aims to: (1) Investigate and compare VDP variability in healthy children and PCD patients; (2) Evaluate VDP against existing breathing tests; and (3) Assess the relationship between VDP variability and changes in PCD quality of life questionnaire scores.
This observational study will recruit 15 PCD participants and extract data from 10 healthy controls from a XeMRI registry. Two study visits will be conducted, separated by 28 days, procedures include Spirometry, Multiple Breath Washout (MBW) testing, Xenon MRI, and a PCD quality of life questionnaire. VDP will be generated using a semi-automated k-means clustering approach. Baseline characteristics will be summarized using descriptive statistics, and statistical tests will determine VDP variability and compare it with secondary measures.
Drawing from similar pediatric cystic fibrosis study designs, we anticipate increased VDP variability in children with PCD, with values comparable to current clinical outcome measures, and associations with the PCD quality of life questionnaire scores.
This study aims to establish XeMRI as a tool for monitoring lung function in children with PCD, determining whether differences in VDP are typical or clinically significant. The results will facilitate clinical translation of XeMRI technology for pulmonary function monitoring and its application in patient care. The findings will be relevant as a novel PCD drug undergoes clinical trials. In conclusion, this research has the potential to enhance PCD management and contribute to the development of effective treatment strategies for this rare genetic disorder.
SESSION #3: BASIC SCIENCE
Moderator:
Georgina Barnabas
Participants:
Pamela Bai
Viviana Li
10:00 –11:30 AM
In-Person: Chieng
Family Atrium
Heather Lu
Solana Redway-Ziola
Samuel Salitra
Liam Stanley
Selina Sun
Sarah Zhang
Zurui Zhu
SESSION #3 Poster #19
Pamela Bai
Watch In-Person:
Thursday, July 27 | 10:00 - 11:30 am
Chieng Family Atrium, BCCHR
Undergraduate Student, University of British Columbia | Supervisor: Stefan Taubert
Investigating the role of efk-1/eEF2K in translation regulation in the C. elegans starvation response
Pamela Bai,
Judith
Yan, Stefan Taubert
Background: Aberrant activation of cellular stress response pathways is prevalent in pediatric cancers and childhood diabetes. Specifically, many cancers feature inappropriate activation of the starvation response regulatory kinase, efk-1/eEF2K. In cancer cells, efk-1/eEF2K promotes acute starvation survival by phosphorylating its target EEF-2/eEF2 and thus attenuating translation elongation. efk-1/eEF2K is also known to attenuate translation initiation by phosphorylating eIF2a during prolonged oxidative stress. To study how efk-1/eEF2K promotes starvation survival, we use the genetic model organism C. elegans. In the nematode worm C. elegans, efk-1/eEF2K is conserved in its ability to phosphorylate EEF-2/eEF2 and to promote starvation survival. However, it is unknown whether efk-1 promotes starvation survival through the canonical pathway of EEF-2/eEF2 phosphorylation, and/or via the alternative mechanism of eIF2a phosphorylation.
Hypothesis: I hypothesize that the kinase efk-1 promotes starvation survival by phosphorylating translation factors eEF2 and/or eIF2a to decrease translation elongation and/or initiation, respectively.
Methods: Wild-type and efk-1 mutant worms were either fed or starved acutely for 8 hours before extracting protein samples. Western blotting was used to quantify expression levels of EEF-2, phospho-EEF-2 (p-EEF-2), p-eIF2a, and tubulin, which were visualized via film and chemiluminescence imaging (Vilber Fusion FX). Normalized EEF-2, p-EEF-2, p-eIF2a levels were quantified in ImageJ. The experiment was also performed in wildtype C. elegans starved chronically for 0, 4, and 9 days.
Results: Consistent with mammalian data, p-EEF-2 is solely dependent on efk-1 in unstressed conditions. However, in 8-hour acutely starved wild-type C. elegans, p-EEF-2 levels did not increase and p-eIF2a levels increased slightly. In 4 and 9-day chronically starved C. elegans, p-EEF-2 levels significantly decreased with starvation duration, while p-EIF2a levels slightly increased.
Conclusions: In C. elegans, efk-1 may not regulate starvation survival by p-EEF-2 induction either in acute or chronic starvation. It is possible that efk-1 promotes starvation survival via p-eIF2a induction instead. To test this, we will quantify p-eIF2a levels in chronically starved efk-1 mutant C. elegans in the future. We will also use CRISPR to construct a kinasedead efk-1 mutant to determine if efk-1 kinase activity is required for starvation survival.
Congratulations to Pamela on receiving a UBC Faculty of Medicine Summer Studentship & NSERC Undergraduate Student Research Awards
SESSION #3 Poster #20
Viviana Li
Watch In-Person:
Thursday, July 27 | 10:00 - 11:30 am
Chieng Family Atrium, BCCHR
Undergraduate Student, Johns Hopkins University | Supervisor: Dan Goldowitz
The Role of Mab21l1 in Cerebellar and Neurodevelopmental Disorders
Viviana Li, Dan Goldowitz, Joanna Yeung
Background: Pax6 is a master control gene in several regions of development and is a transcription factor that regulates downstream target genes. A recent single-cell RNA-sequence analysis examining the transcriptome of Pax6 and Pax6null cerebellum found that Mab21l1 is expressed in glutamatergic lineages, including the granule cells in the developing cerebellum. In addition, the gene expression of Mab21l1 is downregulated in organisms that lack Pax6, suggesting that it is normally under the control of Pax6. Earlier work of the parental gene Mab21 has shown its expression in the developing mouse cerebellum; however, more detailed studies have yet to examine the developmental role of Mab21l1. It is recognized that the Mab-21 family of proteins is involved in cell fate determination, regulation of cell proliferation and differentiation in the developing nervous system. A rare human genetic disorder that includes intellectual disability and cerebellar hypoplasia is identified as a mutation in Mab21l1 causing cerebral, occipital, craniofacial, genital (COFG) syndrome, potentially due to an impairment of the TGF-β/BMP pathway.
Objective: This project examines the developmental expression of the Mab21l1 gene and the role it may have regarding cerebellar development in the mouse, highlighting potential cerebellar and neurodevelopmental disorders that could arise from deficiencies of this gene. This is achieved by analyzing the gene interactions and identifying the regulatory targets of Mab21l1 in the developing cerebellum.
Methods and Analysis: To investigate the relationship between Mab21l1 and Pax6, cerebella dissected from wildtype and Pax6-null mutant mice at varying ages will be examined using in situ hybridization (ISH) and immunohistochemistry (IHC) techniques to determine the spatial expression of Mab21L1 transcript and protein, respectively. The potential downstream target genes of Mab21L1 will be explored using bioinformatics analysis, and the top candidate will be further studied using ISH or IHC.
Outcomes: Through the application of bioinformatics, it is discovered that Mab21l1 mRNA can regulate the BMPmediated pathway during ocular development. This finding can apply to its role in the cerebellum as BMP4 is a key regulator in neuronal development from neural precursor cells in the embryonic, postnatal, and injured CNS. Although several downstream genes of Mab21l1 have been determined, more information is needed to analyze the role of Mab21l1 in the cerebellum.
SESSION #3 Poster #21
Heather Lu
Watch In-Person:
Thursday, July 27 | 10:00 - 11:30 am
Chieng Family Atrium, BCCHR
Undergraduate Student, University of British Columbia | Supervisor: Clare Beasley
Effects of Exercise and the Antipsychotic Drug Olanzapine on Microglia in the Hippocampus of Rats
Heather Lu, Clare Beasley
Background: Schizophrenia is a mental disorder that is characterized by the presence of psychosis and commonly develops in late adolescence or early adulthood. Decreased volume of the hippocampus, a brain region essential for learning and memory, has been associated with this disorder. Antipsychotic medications, such as olanzapine, are used to treat schizophrenia, but can have adverse effects such as weight gain. We have previously reported that olanzapine decreases hippocampal volume in sedentary rats, and that exercise prevents this volume loss. Notably, lower hippocampal volume is correlated with increased abdominal fat. While the biological causes of olanzapine-associated hippocampal volume loss and the prevention of volume loss by exercise remain unknown, there is evidence that exercise reduces hippocampal inflammation in rats. Since excess abdominal fat is associated with neuroinflammation, these observed volume changes could implicate brain immune mechanisms.
We hypothesize that olanzapine reduces hippocampal volume via increased density and activation of microglia, brain cells that mediate neuroinflammation. We further propose that exercise decreases microglial density and activation, alleviating olanzapine-induced inflammation.
Objective: To determine whether microglial density and activation are increased in the dentate gyrus of the hippocampus of rats following olanzapine treatment, and if microglial density and activation are ameliorated by exercise.
Methods: In a previous study, rats were administered olanzapine or vehicle, and assigned to running wheel exercise or sedentary conditions for 9 weeks. In the current project, light microscopy images of hippocampal tissue sections from these rats, stained for the microglial marker IBA-1, were analyzed. The areas of the granule cell layer and subgranular zone of the dentate gyrus and microglia count were quantified using Image-Pro software. Microglial density was calculated as the microglia count per unit area for each region.
Results: Results are currently being analyzed.
Conclusion: Findings from this study will contribute to the understanding of the effects of chronic antipsychotic use. This may lead to improved medications or therapeutic treatments, such as exercise, for individuals with schizophrenia.
SESSION #3 Poster #22
Solana Redway-Ziola
Watch In-Person:
Thursday, July 27 | 10:00 - 11:30 am
Chieng Family Atrium, BCCHR
Undergraduate Student, University of Waterloo | Supervisor: Todd Woodward
How important are task diagrams for interpreting HDR shapes?
Solana Redway-Ziola, Todd Woodward
Background/Introduction: Hemodynamic responses (HDR) from Blood Oxygen Level Dependent (BOLD) signalling are generated from brief stimuli that are dependent on changes in blood flow, volume and oxygenation. BOLD is the technique used in fMRI to generate images and the HDR shapes. BOLD signalling is used while participants complete tasks in order to measure changes in different areas of brain activation. Task diagrams are created to visually represent the flow of the task-based event and the step-by-step breakdown of the process that the participant undertakes.
Purpose: The purpose of the analysis is to determine and communicate the importance of task diagrams as a tool to interpret HDR shapes from BOLD signalling.
Methods: Previous task-based experiments that produced a HDR curve from BOLD signalling were analyzed. For example, we studied experiments that tested paired associates memory encoding, memory recall and imagination, and working memory. Then by comparing the HDR shapes with the task diagrams specific to each task, we were able to compare the changes to the curve that correlates to what is happening in the task.
Significance: It is difficult to understand the HDR curve without the use of task diagrams. Task diagrams allow us to better determine the specific reason for the changes of the HDR shape. We have improved the prior task diagrams to include specific breakdowns of the time interval of the task as a step-by-step process. This update allows for a more concise reasoning of changes in neural network activation. For example, in the Functional Brain Networks Underlying Memory Recall and Imagination study, there was a rise in the estimated HDR signalling. This increase was correlated to the same time interval that individuals were instructed to press buttons, including during the completion of the rating scales. Therefore, by using this task diagram, we were able to show that the reason for the increased estimated HDR was because of the increase in interacting stimuli in the environment that required them to pay attention. Overall, task diagrams can help clearly communicate results of an experiment, especially ones that use HDR shapes, and for that reason it can be a significant tool in scientific research.
SESSION #3 Poster #23
Samuel Salitra
Watch In-Person:
Thursday, July 27 | 10:00 - 11:30 am
Chieng Family Atrium, BCCHR
Undergraduate Student, University of British Columbia | Supervisor: Gregor Reid
Long-term Co-Culture as a Model of B-ALL Leukomogenesis
Samuel Salitra, Tanmaya Atre, Ali Farrokhi, Gregor Reid
B-cell Precursor Acute Lymphoblastic Leukemia (B-ALL) is the most common pediatric malignancy, accounting for roughly 25% of childhood cancer diagnoses in Canada. Almost one third of cases present with the hyperdiploid sub-type (HDALL), making it the single largest contributor to ALL incidence peak in 3-5 year-olds. HD-ALL begins in-utero, where B-cell precursors acquire chromosomal abnormalities, arresting their development and giving rise to a small population of clinically silent Leukemia-initiating-cells (LIC). Subsequent oncogenic events transform the LIC into a malignant state, initiating a program of uncontrolled proliferation in the bone marrow, blood, and extra-medullary sites
Our lab has established that HD-ALL LIC can be sustained for many weeks by co-culture on bone marrow stromal cells (BMSC). These extended cultures may be sufficient to observe transformation of LIC into HD-ALL cells for the first time in vitro. However, a standardized analysis of this transformation has not been conducted and the associated mechanisms remain unclear. To address this, we performed a longitudinal analysis of LIC in long-term co-culture with BMSC.
LIC isolated from the bone marrow and spleen of mice predisposed to HD-ALL were seeded on established BMSC cultures. Cell number, viability, and immuno-phenotypic markers were recorded weekly periods of up to 3 months. Transformation was then characterized using cell surface marker expression, IL-7 dependence, and adoptive transfer experiments.
LIC tended to remain stable in number and viability throughout the first month of co-culture, which was subsequently followed by a period of expansion in month 2. Prior to day 35, 0/11 co-cultures had doubled in cell number. However, by day 50, 5/9 co-cultures exhibited increases in cell number greater than 2x their number at day 35. Changes in cell number corresponded to a shift away from the baseline LIC immunophenotype.
Ex-vivo murine LIC and leukemic cells are also currently being compared to LIC at multiple timepoints in-vitro via bulk RNA-sequencing. These analyses will allow further insight into the changes undergone by LIC in our new in-vitro model of leukemogenesis. This would improve our understanding of HD-ALL biology and facilitate the discovery of points at which the disease can be arrested.
Congratulations to Samuel on receiving a BC Children’s Hospital Research Institute Summer Studentship, UBC Faculty of Medicine Summer Studentship, Andy & Lena Chabot Studentship for Undergraduates, Cancer Research Society
SESSION #3 Poster #24
Liam Stanley
Watch In-Person:
Thursday, July 27 | 10:00 - 11:30 am
Chieng Family Atrium, BCCHR
Undergraduate Student, McGill University | Supervisors: Heather Denroche & Bruce Verchere
Antigen presentation and T cell responses to multicargo lipid nanoparticles in type 1 diabetes
Liam Stanley, Lindsay P. Pallo, Victoria Ng, Sam Chen, Yuen Yi C. Tam, Heather
C. Denroche, C. Bruce Verchere
Type 1 diabetes mellitus (T1D) is an autoimmune disease caused by the destruction of insulin-producing beta cells in the pancreas by auto-reactive T cells that recognize and target multiple beta-cell epitopes. These T cells are activated by antigen-presenting cells (APCs) presenting beta-cell antigens in an inflammatory context. Tolerogenic APCs that present the same beta-cell antigens and immune-regulatory signals to autoreactive T cells can induce immune tolerance responses in these T cells and are a promising therapeutic approach for T1D. Our preliminary data has shown that co-delivery of mRNA-encoded diabetes antigens and immune modulators to APCs using lipid nanoparticles (LNPs) delays diabetes in the NOD mouse model of T1D. We hypothesize that LNPs co-delivering diabetes autoantigens and immune modulators induces tolerance responses in antigen-specific T cells. We are testing this hypothesis by 1) validating presentation of mRNA-encoded antigen by APCs in vitro and 2) assessing T cell responses to LNP-treated APCs. To achieve these aims we are using in vitro proliferation assays in which bone marrow-derived dendritic cells are treated with LNPs carrying mRNA-encoded antigens with/without immune modulators. These cells are then cocultured with antigenspecific or polyclonal CD4 helper T cells or CD8 cytotoxic T cells, before proliferation of T cells is measured using flow cytometry. Expected results should show that the APCs presenting mRNA-encoded antigens without immunomodulators induce high levels of antigen-specific T cell proliferation. We also expect that presentation of the same antigens co-delivered with immune modulators will reduce antigen-specific T cell proliferation. In addition we anticipate that antigen and immunomodulator co-delivery may induce regulatory T cells.
SESSION #3 Poster #25
Selina Sun
Watch In-Person:
Thursday, July 27 | 10:00 - 11:30 am
Chieng Family Atrium, BCCHR
Undergraduate Student, New York University | Supervisor: Wyeth Wasserman
Identifying Enriched Terms in PubMed Abstracts for Distinct Transcription Factors using Advanced Natural Language Processing and Machine Learning Techniques
Selina Sun, Wyeth Wasserman
Background: With an ever-expanding pool of articles published on PubMed, manual curation and synthesis of knowledge regarding specific genes has become a challenge. Leveraging Natural Language Processing (NLP) tools and Machine Learning algorithms, we can now efficiently process vast amounts of data and extract insightful data profiles and conclusions from a multitude of articles.
Objective: This study seeks to identify terms that are significantly enriched in a foreground corpus (a set of documents pertaining to a specific transcription factor) compared to a background corpus (documents pertaining to any transcription factor).
Methods: In the initial stages of data pre-processing, we utilized SciSpacy for lemmatizing words from PubMed abstracts and stored the structured information in a MongoDB database. Acknowledging a Class Imbalance problem (i.e., far fewer foreground articles than background ones), we investigated mitigative strategies such as Synthetic Minority Over-sampling Technique (SMOTE) and assigning class weights. Subsequent to this, we experimented with a variety of analytical techniques and tools, including performing Chi-Square tests to identify enriched terms. Further, we leveraged Term Frequency-Inverse Document Frequency (TF-IDF) calculations to generate an alternate set of outputs. Several Machine Learning techniques, including Random Forest, eXtreme Gradient Boosting (XGBoost), Logistic Regression, and Multinomial Naive Bayes were employed to yield distinct results. We used scikit-learn’s Grid Search method for model hyperparameter tuning, with F1 scores set as the target for optimization. The enriched words were identified through feature importance analysis in the Machine Learning algorithms. For non-interpretable algorithms, we employed SHAP (SHapley Additive exPlanations) to generate graphical interpretations.
Significance: One goal of this study is to generate a Word Cloud visualization for each human transcription factor, grounded on relevant PubMed articles. These visualizations can offer concise, yet comprehensive overviews of specific transcription factors, hence providing a time-efficient strategy for researchers to gain knowledge regarding individual transcription factors. Future works will incorporate these same transcription factor data profiles into knowledge relationship graphs well suited to modern artificial intelligence methods.
SESSION #3
Poster #26
Sarah Zhang
Watch In-Person:
Thursday, July 27 | 10:00 - 11:30 am
Chieng Family Atrium, BCCHR
Undergraduate Student, University of British Columbia | Supervisor: Bruce Verchere
Immune response to lipid nanoparticle delivered therapies in type 1 diabetes
Sarah Zhang, Victoria Ng, Lindsay P. Pallo, Sam Chen, Yuen Yi C. Tam, Heather C. Denroche, C.
Bruce Verchere
In type 1 diabetes (T1D), antigen presenting cells including dendritic cells (DCs) activate effector T cells against autoantigens produced by insulin-producing beta cells. Lipid nanoparticle (LNP) technology provides a method of antigen-specific immunotherapy for autoimmune diseases by enabling drug delivery to antigen presenting cells, with the goal of inducing immune tolerance and reducing the need for broad immunosuppression. We hypothesize that LNPs delivering immune modulators and mRNA encoded T1D autoantigens can tolerize DCs to promote the proliferation of regulatory T cells (Tregs).
Using a T1D mouse model, 7-week-old NOD mice were intraperitoneally immunized with either vehicle or LNP formulations containing 5 µg mRNA, either with or without immune modulators. When mice turned 9 weeks old, spleens were collected for flow cytometry to quantify Tregs and immune markers of tolerance, including cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1). Treatment groups receiving T1D antigen had an increased frequency of CD25-FoxP3+ Treg and PD-1+ T cells compared to irrelevant antigen- and vehicle-injected control groups. This indicates that LNPs carrying T1D autoantigen and immune modulators induce Tregs, providing insight into their mechanism of action. Future studies will investigate whether repeated immunizations can induce a more robust Treg response and measure additional T cell populations, such as Tr1s, that play a key role in establishing immune tolerance.
SESSION #3 Poster #27
Zurui Zhu
Watch In-Person:
Thursday, July 27 | 10:00 - 11:30 am
Chieng Family Atrium, BCCHR
Undergraduate Student, University of British Columbia | Supervisor: Jonathan Bush
Development of Rhabdoid Tumor Patient-Derived Xenografts Using the Chorioallantoic Membrane System
Zurui Zhu, Tariq Bhat, Seohee An, Jonathan Bush
Background: Rhabdoid tumors are highly aggressive tumors that typically occur in infancy in the brain (called atypical teratoid/rhabdoid tumors), and in the kidneys and soft tissues (called malignant rhabdoid tumors). Unfortunately, patient samples of rhabdoid tumors are difficult to obtain because these tumours are often not suspected at the time of triaging and are not encountered frequently. Collaboration with the Bush and Lim lab has developed a unique, first-inCanada pipeline for pediatric tumor cryopreservation and the development of patient-derived xenografts (PDXs) using the chorioallantoic membrane (CAM) system which allows propagation of tumor tissue for expanded experimental use. This system has been optimized using more common tumors, including non-viably frozen tumor samples, and we aim explore the role of CAM as a method to develop PDXs of rare tumors from a clinical archival collection that are not viably cryopreserved.
Aims:
1. Demonstrate that the CAM system is suitable for PDX development using snap frozen rhabdoid tumor samples.
2. Describe the histologic appearance of rhabdoid tumors modeled in the CAM system.
3. Understand the tumor differences between CAM generated PDX tumors at various CAM passages.
Methods: Snap frozen samples from 4 different types of rhabdoid tumours were implanted into CAMs and grown for five days. Tumours from the CAMs are then made into formalin-fixed paraffin-embedded (FFPE) tissue specimens or directly implanted into a new CAM for the next passage. For each passage, FFPE specimens are collected and sectioned to obtain slides which are stained using hematoxylin and eosin (H&E) staining or immunohistochemistry (IHC) for the identification of tumour cells.
Results: Preliminary results show viable tumour cells for a rhabdoid tumour sample in the first passage according to H&E staining and IHC. H&E staining and IHC will also be performed on the other tumour samples as well as the same tumour sample from later passages to understand the tumour differences between different passages.
Congratulations to Zurui on receiving a UBC Faculty of Medicine Summer Studentship
SESSION #4: CLINICAL
Moderator:
Thais Rangel
Bousquet Carrilho
Participants:
Farah Tabassum Azim
10:00 –11:30 AM
In-Person: Chieng
Family Atrium
Rachel Bates
Kate Borgert
Naomi Choong
Jasleen Grewal
Setareh Setayesh
Jack Pearce Wong
Cindy Zhang
SESSION #4 Poster #28
Farah Tabassum Azim
Watch In-Person:
Thursday, July 27 | 10:00 - 11:30 am
Chieng Family Atrium, BCCHR
Undergraduate Student, University of British Columbia | Supervisor: Tim Bhatnagar
A Novel Use of Motion Capture to Quantify Kinematic Changes Following myoActivation® Therapy
Farah T. Azim, Karen Davies, Diane Wickenheiser, Mona Behrouzian, Gail Jahren, Nicholas West, Lise Leveille, Gillian R. Lauder, Tim Bhatnagar
Introduction: The Complex Pain Service (CPS) interventional care team at BC Children’s Hospital is a multidisciplinary service which provides holistic pain management for pediatric patients. Children with chronic myofascial pain are offered myoActivation® treatment as part of routine clinical care. MyoActivation® is comprised of (i) movement tests to assess pain and range of motion (ROM), and (ii) a needling technique to activate muscles, release fascial restrictions and/or scar tissue. Following treatment, an immediate change in ROM is observed which has previously not been quantified in an objective manner.
Aim: To demonstrate the use of motion capture to objectively quantify changes in participant ROM and speed of motion during the myoActivation® movement tests.
Methods: Five participants were recruited as part of this non-randomized, longitudinal pilot study (REB #H20-00463) to receive myoActivation® in The Motion Lab at Sunny Hill Health Centre. The number and location of myoActivation® treatments received were individualized based on each participant’s unique pain history. The myoActivation® movement tests were performed at baseline and after all interventions. These movements were collected and analyzed using motion capture technology with a 12-camera marker based Qualisys motion capture system and Visual3D. Due to the unique nature of the treatments received, participants served as their own control and no statistics and effect size calculations were performed.
Results: Five females of median age of 16 (16-18 years) were included and all participants were experiencing chronic pain for over a year. The CPS physician performed a qualitative assessment to assess any changes in ROM for each participant. The following two tests were predicted to change for all participants: extension arms down and flexion arms down. Most participants demonstrated a significant improvement in ROM and speed in performing the movements.
Discussion: This study demonstrated the feasibility of using clinical motion analysis to provide an objective and quantitative measure of assessing myoActivation®. The improvement in ROM and speed was quantified using motion capture technology. Findings from this study warrant a need for a larger clinical trial to perform further analyses.
Congratulations to Farah on receiving a BioTalent Canada Award
SESSION #4 Poster #29
Rachel Bates
Watch In-Person:
Thursday, July 27 | 10:00 - 11:30 am
Chieng Family Atrium, BCCHR
Undergraduate Student, University of British Columbia | Supervisor: Gillian Lauder
The effect of intravenous lidocaine infusion on intraoperative neurophysiological monitoring in adolescents during surgery for idiopathic scoliosis correction; a retrospective study
Rachel Bates, Fiona Cave, Bradley Hofmann, Nicholas West, Jeffrey N. Bone, Firoz Miyanji, Gillian Lauder
Purpose: Posterior spinal instrumentation and fusion (PSIF) is a common surgery at BC Children’s hospital for the correction of adolescent idiopathic scoliosis. Intraoperative neurophysiological monitoring (IONPM) assesses intraoperative spinal cord function during PSIF. IONPM includes the monitoring of Somatosensory Evoked Potentials (SSEPs) and Transcranial Electric Motor Evoked Potentials (MEPs). IONPM can be affected by some anesthetic agents. Intravenous lidocaine therapy is used to improve postoperative pain and minimize opioid requirements following adolescent PSIF procedures. However, its effect on IONPM during adolescent scoliosis surgery is unknown.
Objective: To investigate the effect of intravenous lidocaine infusion on monitoring of SSEPs and MEPs during adolescent scoliosis surgery.
Methods: This was a retrospective study of single-stage PSIF procedures between January/2012 and February/2021 with data abstracted by chart review. Anesthetic and surgical information, IONPM events and hourly snapshots were retrieved for each patient from archived data held within the neurophysiology department. A reportable event was defined as a decrease of 50% MEP or SSEP amplitude from baseline or an increase of 10% SSEP latency from baseline. Number of IONPM events and hourly snapshot changes from baseline for upper and lower limb MEPs and SSEPs were compared between two groups: 1) patients who received intraoperative lidocaine infusion and 2) a random sample of controls who did not receive a lidocaine infusion.
Results: Data were available from 39 cases with lidocaine infusion and 42 cases with no lidocaine infusion. Of these, 60 were female (75.9%), and the median age [interquartile range] was 14.0 [12.2-15.0] years. Out of all recorded reportable events, 25/55 (45.4%) occurred in patients receiving lidocaine and 30/55 (54.5%) occurred in patients who did not receive lidocaine. Median time to first event was similar between groups (Hazard Ratio[HR]=1.13,95%CI,0.61-2.09).
Hourly snapshot data showed no significant effect of lidocaine on MEP amplitudes in both lower (median difference [MD]41.91,95%CI,-304.46-388.27;p=0.182) or upper limbs (MD-279.00,95%CI,-562.45-4.44;p=0.054), and no effect on SSEP amplitudes in lower (MD16.41,95%CI,-17.68-50.50;p=0.345) or upper limbs (MD-2.37,95%CI,-14.51-9.76;p=0.701).
Conclusion: We found no detriment of intraoperative lidocaine infusion on IONPM during adolescent idiopathic scoliosis surgery. Despite limitations associated with the retrospective nature of the study, these findings suggest appropriate variables and design considerations for a subsequent prospective randomized controlled trial.
Congratulations to Rachel on receiving a Biotalent Canada Award
SESSION #4 Poster #30
Kate Borgert
Watch In-Person: Thursday, July 27 | 10:00 - 11:30 am
Chieng Family Atrium, BCCHR
Undergraduate Student, Queen’s University | Supervisor: William T. Gibson
Genotype-Phenotype Correlations in SETD1B-Related Neurodevelopmental Disorder
Kate Borgert, William Gibson
Background: Disease phenotypes can be influenced by both genetic and environmental factors. Such genotypephenotype correlations can predict physical characteristics or abnormalities an individual with a particular mutation may display. SETD1B is a histone methyltransferase within an epigenetic regulatory complex called Complex Protein Associated with Set1 (COMPASS). The COMPASS complex directs the methylation of histone 3 at lysine 4s. Rare variants in the SETD1B gene can hinder the protein functionality causing altered gene transcriptional programming with downstream effects. This disease state is referred to as SETD1B-related neurodevelopmental disorder (SETD1B-NDD). While there is large phenotypic heterogeneity in SETD1B-NDD, global developmental delay, intellectual disability, and seizures are commonly observed in these patients.
Objective: To find genotype-phenotype correlations in SETD1B-NDD.
Methods: To expand our understanding of SETD1B-NDD disease phenotypes, we conducted interviews with newly identified patients and their families referred throughout the globe to our lab. To find possible unique genotypephenotype correlations, we plan to identify the regional variation within SETD1B with the heterogeneity and severity of patient phenotypes. Additionally, we are planning to collect whole blood samples from patients and perform long-read whole genome sequencing to create an epigenome-wide profile of SETD1B.
Preliminary Results: To date, we have identified several unique phenotypes, including early puberty and recurrent pre-cancerous nevi.
Significance: Creating an epigenome-wide profile of SETD1B will help identify epigenetic changes induced by rare variants and give more insight into the downstream effects that result in SETD1B-NDD disease phenotypes. By characterizing genotype phenotype correlations in SETD1B-NDD, personalized patient management plans will be better informed, leading to increased quality of life for SETD1B-NDD patients.
SESSION #4 Poster #31
Naomi Choong
Watch In-Person:
Thursday, July 27 | 10:00 - 11:30 am
Chieng Family Atrium, BCCHR
Undergraduate Student, University of British Columbia | Supervisor: Jaime Guzman; Rheumatology Research Team
The Relationship of Fatigue, Pain Interference and Physical Disability in Children Newly Diagnosed with Juvenile Idiopathic Arthritis: Results from the CAPRI Registry
Naomi Choong, Michelle Batthish, Roberta Berard, Gaëlle Chédeville, Jean-Philippe Proulx-Gauthier, Jaime Guzman
Background: Juvenile idiopathic arthritis (JIA) is the most prevalent childhood rheumatic disease worldwide and characterized by persistent joint inflammation. Despite effective contemporary treatments, children with JIA often suffer from pain, fatigue and physical disability. Studies show that fatigue can have a negative impact on pain intensity and functional ability. Pain interference has also been associated with physical disability. However, there is a lack of knowledge on the relationship between fatigue and pain interference in JIA. Additionally, the mechanisms by which pain interference and physical disability are related are not clear.
Objective: To investigate whether there is a significant relationship between fatigue and pain interference, and test whether fatigue mediates the relationship between pain interference and physical disability.
Methods: Data from the Canadian Alliance of Pediatric Rheumatology (CAPRI) Registry collected from newly diagnosed JIA patients between February 2017 and February 2023 was analyzed. Physical disability, fatigue, and pain interference were measured using standardized parent-proxy questionnaires. Relationships between variables were analyzed using Pearson’s correlation and multiple linear regression. Structural equation modeling (SEM) will later be used to test if fatigue mediates the relationship between pain interference and physical disability.
Results: The study included 855 patients, 61% female, with a median age of 9.3 years at enrollment. The most frequent JIA category was oligoarthritis (44%). Fatigue was significantly and strongly correlated with pain interference (r = .72, p < .001, 95% CI [.69, .75]) and physical disability (r = .60, p < .001, 95% CI [.55, .65]). Pain interference was also strongly associated with physical disability (r = .63, p < .001, 95% CI [.60, .67]). After adjusting for confounders, fatigue (b = .028, p < .001), and pain interference (b = .040, p < .001) both independently predicted physical disability. In a model where fatigue and pain interference were adjusted for each other and confounders, pain interference (b = .028, p < .001) was a stronger predictor of physical disability than fatigue (b = .013, p < .001). The R2 value for this model was 0.53. The larger drop in the fatigue beta coefficient when pain interference was included in the regression suggests it may be a mediator. SEM analysis to investigate mediation fully is ongoing.
Implications: Findings from this study provide insight into the importance of assessing and addressing fatigue and pain interference in clinical settings to mitigate physical disability in the early stages of JIA.
SESSION #4 Poster #32
Jasleen Grewal
Watch In-Person:
Thursday, July 27 | 10:00 - 11:30 am
Chieng Family Atrium, BCCHR
Undergraduate Student, Queen’s University | Supervisor: Suzanne Vercauteren
Electronic vs. Paper: Participant Satisfaction with Informed Consent for Biobanking
Jasleen Grewal, Veronica Chow, Ashton Ellis, Jonathan Bush, Suzanne Vercauteren
Background: Human biospecimens, linked with medical health records, enable researchers to conduct a diverse range of genetic or biomarker studies. Patients undergoing collection procedures at BC Children’s Hospital, and caregivers on their behalf can consent to donate extra or left-over samples to the BioBank where they are de-identified, cryopreserved, and stored for future ethically-approved research. Recently, the BCCH BioBank has adopted an electronic consent method for participant recruitment. Traditionally, biobanks have recruited patients through targeted mailings, in-person encounters with research assistants, or opt-out methods. Mailing and in-person recruitment strategies are effective but are timeconsuming and expensive to scale in terms of personnel and resources.
Objective: The study will explore and compare patient engagement and satisfaction with electronic informed consent and traditional paper consent methods for sample collection at the BCCH BioBank. Through survey responses, the study aims to better understand participant reasoning for selecting paper or electronic consent platforms and characterize participants’ experiences based on their choice. Recognized barriers to biobank participation include literacy and language, age, cultural differences, and public distrust. Through data collection and survey analysis, the aforementioned barriers can be studied in the electronic consent process and compared to traditional consenting to improve participant recruitment and satisfaction.
Methods: Upon initiation of the BCCH BioBank in-person consent process, every patient is given a choice of paper or electronic consent platforms. After participants consent to the BioBank they are invited to complete an anonymous voluntary e-consent opinion survey. Survey responses will be examined to track participant satisfaction, engagement, and perception of either choice of consent platform. Based on these results, recommendations will be made to improve or remodel consent delivery for the BCCH BioBank.
Significance: Informed consent for the research use of biospecimens and clinical data is an essential component of precision and translational medical research. Studies examining the implementation of electronic consent for biobanking in the pediatric or British Columbian setting are absent from the literature. Results from this project may identify issues relating to informed consent, diversification in sample collection, and scalability and cost-effectiveness of the process of biobanking recruitment for personnel and resources.
Congratulations
SESSION #4 Poster #33
Setareh Setayesh
Watch In-Person:
Thursday, July 27 | 10:00 - 11:30 am
Chieng Family Atrium, BCCHR
Undergraduate Student, McGill University | Supervisor: Anamaria Richardson
Graphic Arts-based Thematic Analysis: A Novel Methodology to Promote Equity in Exams Under Anesthesia
Setareh Setayesh, Elizabeth Nijdam, Aaron K. W. Ooi, Anamaria Richardson
Background: The Exams Under Anaesthesia (EUA) project is a quality improvement project seeking to better understand the process of EUAs for children with complex behaviours and promote health equity by identifying areas for improvement. Children with complex behaviours include those with autism, intellectual impairment, limited verbal capacity, and genetic syndromes. For these children, medical exams and interventions can be very difficult and result in aggression, self-injury, and bolting. Sedation is used to facilitate this process, but it can be very traumatic for children, caregivers, and clinicians. The investigators conducted interviews with parents of children with complex behaviours and collected data from patient chart reviews. As part of the knowledge translation, a parent partner was consulted to create a graphic representation of themes identified in the study. This artwork inspired inquiry into how we may be able to use graphic art as a methodology for thematic analysis of research.
Traditional knowledge creation in research often diminishes and excludes intersectional voices and knowledge translation lacks in its inclusion of a non-academic audience. The objective of this study is to explore new methodologies for thematic analysis of scientific research results with the goal of more authentic knowledge co-creation.
Methods: Graphic artists will be recruited based on criteria including self-identified understanding of the scope of the project and ability to quickly produce work, with priority given to autistic and Indigenous artists. Artists will be provided with 9 recorded and transcribed interviews from the previous study that have been anonymized and de-identified. A workshop will be held to educate artists on the project and finished artwork will be displayed and open to public viewing.
Anticipated Outcomes: The project is exploratory, but we may be able to extract new themes from the data and gain knowledge about how alternative methodologies can be useful in knowledge co-creation.
Implications: Exposing alternative methodologies for knowledge co-creation can allow us to better extract information from data, particularly in order to amplify the voices of marginalised and fringe groups who often have a limited platform to communicate needs and issues.
SESSION #4 Poster #34
Jack Pearce Wong
Watch In-Person:
Thursday, July 27 | 10:00 - 11:30 am
Chieng Family Atrium, BCCHR
Undergraduate Student, University of British Columbia | Supervisor: Jennifer Retallack
Exploring an Accessible Instant Video Telemedicine Tool to Support
Pediatric Critical Care Triage and Transport During the 2022/2023 Pediatric Respiratory Surge
Jack Pearce Wong, Adela Matettore, Jonathan Wong, Steven Brown, Jennifer Retallack
Background: In British Columbia (BC), the vast geography and centralized pediatric tertiary care services requires interfacility transfers to support patient care. These pediatric transports are coordinated through the pediatric intensive care unit (PICU) at BC Children’s Hospital in collaboration with BC Emergency Health Services Patient Transfer Network. In 2022, a surge of pediatric respiratory illnesses overwhelmed existing resources and required rapid collaboration between health agencies. To support transport triaging and medical advice for pediatric patients requiring a higher level of care, GoodSAM Instant Help was rapidly piloted. This platform, widely used in pre-hospital settings, utilizes users’ own smartphones to facilitate two-way video via text link.
Aims: Review the rapid deployment of GoodSAM Instant Help to establish the foundation for continued usage.
Methods: A mixed methods approach was utilized with surveys for physician providers, transfer coordinators, and patient partners. Quantitative data from clinical systems, GoodSAM metrics and surveys were collected with qualitative survey data.
Results: During Nov 2022 - March 2023 consultations to the PICU Transport Advisors increased over 45% (167 compared 114 during the same time period the year prior). Eighty-one of these consultations used the GoodSAM video platform. Surveys were completed by PICU physicians for 32 cases and demonstrated changes in the PICU physician’s perception of the acuity in 38% of responses, and that transport to a tertiary center was averted in 6 cases due to the video consultation. Some minor technical difficulties with the platform were identified. Family partner surveys (n=25) indicated 100% of those surveyed identified benefits of the integration of video into the consultation.
Discussion and Conclusion: This pilot study demonstrates the successful rapid deployment of GoodSAM within the context of pediatric critical care transfers. GoodSAM represents a relatively low barrier technology which can be widely distributed across a large geographic area and used to support emergency room and inpatient providers. Further evaluation of this technology within the context of pediatric interfacility transport and triage is needed. As this was a rapid implementation further robust analysis is ongoing and will supplement initial findings in determining clinical and operational benefits for the usage of this platform.
